PMID- 7800454
TI  - Malignant fibrous histiocytoma of primary omental origin in an infant.
AB  - A case of malignant fibrous histiocytoma occurring in an infant is presented. The
      primary location of the tumor was in the omentum. Sonography showed huge,
      lobulated echogenic masses with cystic areas. CT demonstrated heterogeneously
      enhancing masses with central cystic and necrotic areas. This very unusual
      occurrence of a tumor in infancy with an intraabdominal location is described and
      the radiographic imaging is presented.

PMID- 7800455
TI  - Pediatric barium enema examination: optimizing patient selection with univariate
      and multivariate analyses.
AB  - We prospectively evaluated a total of nineteen symptoms, signs, and laboratory
      findings in 471 of 557 consecutive pediatric patients (from newborn to age 17)
      referred for barium enema examinations, to determine predictors of an abnormal
      study. A univariate analysis was performed, and a logistic regression model was
      developed. The most frequent indicators for the barium enema examinations were
      abdominal pain (48%), constipation (27%) and tenderness (25%). Twenty-two percent
      of the examinations were abnormal, and the most common diagnoses were
      intussusception (n = 22), appendicitis (n = 17), infectious colitis (n = 15), and
      Hirschsprung disease (n = 14). The indicators that were most helpful to predict a
      barium enema abnormality were abdominal mass, leukocytosis, guaiac-positive
      stools, diarrhea, anemia, tenderness, and age less than 1 year. If barium enema
      examinations were performed only when at least one of the predictive indicators
      was present, 29% of examinations would be eliminated, and 4.8% of patients with
      detectable disease would be missed. The data indicate that identification of
      certain clinical variables can provide an effective initial strategy for
      selecting patients to undergo barium enema examinations.

PMID- 7800456
TI  - Intussusception: characteristic radiolucencies on the abdominal radiograph.
AB  - Six hundred and twenty-five sets of supine and erect abdominal radiographs of 288
      patients with the confirmed diagnosis of intussusception (315 episodes) and 310
      patients without intussusception were reviewed retrospectively to determine the
      characteristic radiographic features of intussusception. Among the patients with
      intussusception, 155 episodes (49%) showed a soft tissue mass and nearly half of
      these (71) showed characteristic radiolucencies (target, crescentic, or
      amorphous) in the soft tissue mass. Thirty-five episodes showed the
      radiolucencies on both the supine and erect radiographs; in 16 cases the type of
      radiolucency differed on the two films. In patients without intussusception,
      abnormal radiolucencies were seen in only seven cases (2.3%). Computed tomography
      performed prospectively in five patients showed the radiolucencies in the soft
      tissue mass to be intussuscepted mesenteric fat. We conclude that abnormal
      radiolucencies in the soft tissue mass on plain radiographs are characteristic of
      intussusception.

PMID- 7800457
TI  - Pneumatic reduction of intussusception using carbon dioxide.
AB  - Pneumatic reduction using air has recently become popular for the initial non
      surgical management of intussusception. Since carbon dioxide (CO2) is rapidly
      absorbed from body surfaces, it should theoretically result in less cramping and
      distension following reduction. We reviewed our recent experience with the
      pneumatic reduction of intussusception using CO2 in 26 children. In 22 of these
      the intussusception was reduced (85%). There was one performation with CO2; the
      patient did not suffer any postoperative complications. Five additional children
      who had been treated unsuccessfully with barium had intussusception subsequently
      reduced with CO2. Following CO2 reduction, most children were fed within hours,
      and there were no instances of significant abdominal distension or cramping. We
      conclude that pneumatic reduction of intussusception using CO2 is safe and
      effective, and has the theoretical advantage of more rapid absorption from the
      gastrointestinal tract than air.

PMID- 7800458
TI  - Left ventricular diverticulum: MRI demonstration (congenital broad-based left
      ventricular aneurysm)
AB  - The case presented is that of a 3-year-old boy with an asymptomatic left
      ventricular diverticulum. The value of MRI in the detection and classification of
      this entity is illustrated.

PMID- 7800459
TI  - Reversal of left carotid arterial flow as a sign of type C interruption of the
      aortic arch.
AB  - While performing neurosonography on an 8-day-old baby boy, we noted antegrade
      flow in the right carotid and basilar arteries but retrograde flow in the left
      carotid artery. The child was diagnosed as having a severe cardiac malformation
      and associated interruption of the aortic arch on echocardiography. Our finding
      is explained by the site of interruption-between the innominate and left carotid
      arteries, or type C interruption.

PMID- 7800460
TI  - Dorsal mesodermal sinus associated with annular pancreas and meconium
      peritonitis.

PMID- 7800461
TI  - Ruptured cystic mesenchymal hamartoma: an unusual cause of neonatal ascites.
AB  - Cystic mesenchymal hamartoma is an uncommon benign liver neoplasm usually seen in
      infants with an asymptomatic abdominal mass [1]. We report a neonate who
      presented with a ruptured cystic mesenchymal hamartoma which produced respiratory
      distress due to massive ascites. To our knowledge, this complication has never
      been reported.

PMID- 7800462
TI  - Late-onset Bochdalek hernia with a rare postoperative complication: case report.
AB  - We report a case of a 7-year-old-girl with a late-presenting Bochdalek hernia.
      The postoperative course was complicated by splenic torsion and subsequent total
      splenic infarction. Total splenic infarction due to splenic torsion has been
      reported in children with "wandering spleen" and in incarcerated Bochdalek
      hernias, but to our knowledge, not as a postoperative complication of Bochdalek
      hernia repair.

PMID- 7800463
TI  - Bilateral ureteral obstruction and renal failure due to a perforated appendix.
AB  - Bilateral ureteral obstruction secondary to appendicitis is rare. We here report
      a case in which the obstruction caused anuria and renal failure.

PMID- 7800464
TI  - Gyriform calcification in middle cerebral artery infarct.

PMID- 7800465
TI  - The role of wholistic/configural properties versus global properties in visual
      form perception.
AB  - A distinction has previously been proposed between global properties, defined by
      their position in the hierarchical structure of the stimulus, and
      wholistic/configural properties defined as a function of interrelations among
      component parts. The processing consequences of this distinction were examined in
      five experiments. In experiments 1-4 configural properties (closure and
      intersection) were pitted against component properties (line orientation and
      direction of curvature) and the results showed that discrimination and
      classification performance was dominated by the configural properties. In
      experiment 5 the relative perceptual dominance of type of property
      (configural/nonconfigural) and level of pattern structure (global/local) was
      examined. The results showed that classifications based on the configural
      property of closure were not affected at all by the level of globality at which
      this property varied. Global advantage was observed only with classifications
      based on line orientation. Taken together, the present results suggest that
      configural properties dominate discrimination and classification of visual forms,
      whereas the perceptual advantage of the global level of structure depends
      critically on the type of properties present at the global and local levels.
      These findings are also discussed in relation to findings on texture perception,
      and it is suggested that the perceptual system may be characterized by a
      predisposition for configural properties.

PMID- 7800466
TI  - From geons to structure. A note on object representation.
AB  - Two models of object perception are compared: recognition by components (RBC),
      proposed by Biederman, and structural information theory (SIT), initially
      proposed by Leeuwenberg. According to RBC a complex object is decomposed into
      predefined elementary objects, called geons. According to SIT, the decomposition
      is guided by regularities in the object. It is assumed that the simplest of all
      possible interpretations of any object is perceptually preferred. The comparison
      deals with two aspects of the models. One is the representation of simple objects
      -various definitions of object axes are considered. It is shown that the more
      these definitions account for object regularity and thus the more they agree with
      SIT, the better the object representations predict object classification. Another
      topic concerns assumptions underlying the models: the identification of geons is
      mediated by cues which are supposed to be invariant under varying viewpoints of
      objects. It is argued that such cues are not based on this invariance but on the
      regularity of actual objects. The latter conclusion is in line with SIT. An
      advantage of RBC, however, is that it deals with the perceptual process from
      stimulus to interpretation, whereas SIT merely concerns the outcome of the
      process, not the process itself.

PMID- 7800467
TI  - Local and global factors in visual occlusion.
AB  - Although interest in the phenomenon of visual occlusion is of very long standing,
      only a small number of experimental studies have been reported, and available
      theories fail to give satisfactory explanations of the data. In this paper the
      efficacy of local factors in organising the perception of globally regular
      occlusion patterns is explored. Three experiments are reported in which the
      relative contribution of local and global factors to the salience of percepts is
      investigated. It is demonstrated that local factors play a very important role in
      the perception of these kinds of patterns.

PMID- 7800468
TI  - Local and global minima in visual completion: effects of symmetry and
      orientation.
AB  - The visual information that specifies three-dimensional objects is often
      incomplete because objects occlude parts of themselves and other objects. Yet
      people rarely have difficulty perceiving complete, three-dimensional forms.
      Somehow the visual system seems to 'complete' partially specified objects. The
      perceptual processes underlying this seemingly effortless and immediate
      completion are poorly understood. Sekuler and Palmer designed in 1992 the primed
      matching paradigm for the objective study of completion effects and their
      microgenesis. Results from the paradigm suggest that global processes may play a
      role early in perceptual completion, and that local processes dominate only under
      limited conditions of figural regularity and orientation. These results are not
      consistent with purely local or purely global theories of completion. The
      findings have implications for object perception and representation.

PMID- 7800469
TI  - Invariance from the Euclidean geometer's perspective.
AB  - It is remarkable how well the human visual system can cope with changing
      viewpoints when it comes to recognising shapes. The state of the art in machine
      vision is still quite remote from solving such tasks. Nevertheless, a surge in
      invariance-based research has led to the development of methods for solving
      recognition problems still considered hard until recently. A nonmathematical
      account explains the basic philosophy and trade-offs underlying this strand of
      research. The principles are explained for the relatively simple case of planar
      object recognition under arbitrary viewpoints. Well-known Euclidean concepts form
      the basis of invariance in this case. Introducing constraints in addition to that
      of planarity may further simplify the invariants. On the other hand, there are
      problems for which no invariants exist.

PMID- 7800470
TI  - Aspect graphs for visual recognition of three-dimensional objects.
AB  - Visual representation of three-dimensional (3-D) objects in our environment is a
      crucial question, for human as well as for machine vision. Some basics are
      reviewed of a viewer-centred model of 3-D objects, aspect graphs, which
      represents a 3-D object by all its topologically stable visible image contours
      (its aspects) and by the transitions between stable image contours (the visual
      events). This representation takes only geometrical information about
      discontinuities in depth and in surface orientation into account, and other
      clues, such as shadows, markings, texture, etc, are disregarded. Mathematical
      results give some insight into the relationships between the geometry of a 3-D
      object and the aspect of its image contours, the techniques used to compute an
      aspect graph effectively, and the state of the art of this type of model in
      computer vision. Current research is reviewed on viewer-centred representation in
      cognitive science that seems to indicate that aspect graphs could also have some
      relevance for human vision.

PMID- 7800471
TI  - On so-called paradoxical monocular stereoscopy.
AB  - Human observers are apparently well able to judge properties of 'three
      dimensional objects' on the basis of flat pictures such as photographs of
      physical objects. They obtain this 'pictorial relief' without much conscious
      effort and with little interference from the (flat) picture surface. Methods for
      'magnifying' pictorial relief from single pictures include viewing instructions
      as well as a variety of monocular and binocular 'viewboxes'. Such devices are
      reputed to yield highly increased pictorial depth, though no methodologies for
      the objective verification of such claims exist. A binocular viewbox has been
      reconstructed and pictorial relief under monocular, 'synoptic', and natural
      binocular viewing is described. The results corroborate and go beyond early
      introspective reports and turn out to pose intriguing problems for modern
      research.

PMID- 7800472
TI  - Object recognition under sequential viewing conditions: evidence for viewpoint
      specific recognition procedures.
AB  - In many computational approaches to vision it has been emphasised that object
      recognition involves the encoding of view-independent descriptions prior to
      matching to a stored object model, thus enabling objects to be identified across
      different retinal projections. In contrast, neurophysiological studies suggest
      that image descriptions are matched to less abstract, view-specific
      representations, resulting in more efficient access to stored object knowledge
      for objects presented from a view similar to a stored viewpoint. Evidence
      favouring a primary role for view-specific object descriptions in object
      recognition is reported. In a series of experiments employing line drawings of
      familiar objects, the effects of depth rotation upon the efficiency of object
      recognition were investigated. Subjects were required to identify an object from
      a sequence of very briefly presented pictures. The results suggested that object
      recognition is based upon the matching of image descriptions to view-specific
      stored representations, and that priming effects under sequential viewing
      conditions are strongly influenced by the visual similarity of different views of
      objects.

PMID- 7800473
TI  - Nursing datasource 1994. Volume I. Trends in contemporary nursing education.

PMID- 7800474
TI  - Transcription factor AP-4 participates in activation of bovine leukemia virus
      long terminal repeat by p34 Tax.
AB  - Three 21bp repeats can be found in the bovine leukemia virus long terminal
      repeat, which are crucial for the LTR directed gene expression by the trans
      activator protein Tax. Previous studies demonstrated that the major target of the
      Tax directed activation are the CRE-like elements in the center of these repeats.
      In this work we report that another motif of the 21bp repeats is also required
      for the Tax activation. Gel retardation--with the wild type or mutant 21bp
      repeats--revealed that cellular factors from HeLa cells were specifically bound
      to the center (CRE-like element) and the 3' region of the repeats, which contains
      a CAGCTG consensus AP-4 binding site. In vivo analysis using the synthetic 21bp
      repeats indicated that beyond the consensus CRE-like motif, the AP-4 site is also
      essential for Tax activation. To determine the role of AP-4 in BLV Tax trans
      activation, we used the AP-4 cDNA in antisense transient assays. In the in vivo
      experiments the antisense AP-4 RNA resulted in strongly decreased Tax activation.
      On the basis of these results we conclude that AP-4 is a good candidate of
      cellular factors involved in BLV Tax trans activation.

PMID- 7800475
TI  - The DNA sequence encompassing the transcription start site of a TATA-less
      promoter contains enough information to drive neuron-specific transcription.
AB  - The FE65 gene encodes a nuclear protein of unknown function that is expressed in
      several areas of the rat nervous system during development and in the adult
      animal, particularly in somatic and visceral ganglia. FE65 mRNA is abundant in
      neuronal cell lines, whereas it is barely detectable in non-neuronal cells. We
      identified the two transcription start sites of the FE65 gene and we isolated the
      rat genomic fragment containing one of these two transcriptional start sites. We
      demonstrate that this fragment contains a promoter able to direct an efficient
      transcription of a reporter gene in PC12 cells and in NTERA2 cells upon their
      differentiation with retinoic acid, whereas it functions poorly in non-neuronal
      cells, such as Rat2 fibroblasts and BRL hepatocytes. This promoter is composed of
      two regions. The first includes a cis-element whose removal greatly decreases the
      transcriptional efficiency in all cells examined and which forms similar
      complexes with proteins from PC12 and Rat2 cells. This cis-element binds Sp1 or
      another GC-binding factor. The second cis-element encompasses the transcription
      start site and is still able to direct transcription only in neuronal cells. The
      DNA-protein complexes formed by this cis-element in neuronal cells differ from
      those formed in non-neuronal cells. The analysis of point mutations in this
      region indicates that the proteins that bind to this cis-element interact with
      both overlapping and distinct nucleotide sequences.

PMID- 7800476
TI  - A role for the human DNA repair enzyme HAP1 in cellular protection against DNA
      damaging agents and hypoxic stress.
AB  - The HAP1 protein (also known as APE/Ref-1) is a bifunctional human nuclear enzyme
      required for repair of apurinic/apyrimidinic sites in DNA and reactivation of
      oxidized proto-oncogene products. To gain insight into the biological roles of
      HAP1, the effect of expressing antisense HAP1 RNA in HeLa cells was determined.
      The constructs for antisense RNA expression consisted of either a full-length
      HAP1 cDNA or a genomic DNA fragment cloned downstream of the CMV promoter in
      pcDNAneo. Stable HeLa cell transfectants expressing HAP1 antisense RNA were found
      to express greatly reduced levels of the HAP1 protein compared to equivalent
      sense orientation and vector-only control transfectants. The antisense HAP1
      transfectants exhibited a normal growth rate, cell morphology and plating
      efficiency, but were hypersensitive to killing by a wide range of DNA damaging
      agents, including methyl methanesulphonate, hydrogen peroxide, menadione, and
      paraquat. However, survival after UV irradiation was unchanged. The antisense
      transfectants were strikingly sensitive to changes in oxygen tension, exhibiting
      increased killing compared to controls following exposure to both hypoxia (1%
      oxygen) and hyperoxia (100% oxygen). Consistent with a requirement for HAP1 in
      protection against hypoxic stress, expression of the HAP1 protein was found to be
      induced in a time-dependent manner in human cells during growth under 1% oxygen.
      The possible involvement of a depletion of cellular glutathione being linked to
      the hypoxic stress-sensitive phenotype of the antisense HAP1 transfectants came
      from the finding that they also exhibited hypersensitivity to buthionine
      sulphoximine, an inhibitor of glutathione biosynthesis. We conclude that the HAP1
      protein is a key factor in cellular protection against a wide variety of cellular
      stresses, including DNA damage and a change in oxygen tension.

PMID- 7800477
TI  - Kinetic and equilibrium binding studies of the human papillomavirus type-16
      transcription regulatory protein E2 interacting with core enhancer elements.
AB  - The human papillomaviruses (HPVs) are a family of DNA viruses which cause benign
      tumours of the skin and mucosa that infrequently progress to malignant carcinoma.
      The E2 open reading frame of HPV is thought to encode a papillomavirus-specific
      transcription factor which also has a role in viral replication. The E2 proteins
      of all papillomaviruses studied to date have been shown to bind specifically to
      the common conserved sequence ACC(N)6GGT found at multiple locations in their
      genomes. In the case of HPV-16, a 'high risk' genital papillomavirus, the E2
      protein is thought to negatively regulate expression of the major viral
      transforming genes E6 and E7, which have been directly implicated in the
      oncogenic process. However, little information exists concerning the relative or
      absolute affinities of the native HPV-16 protein for its palindromic recognition
      sequences; moreover, interpretation of any transcription or replication phenomena
      attributed to this protein is more complicated in the absence of such data. Here
      we describe the overexpression, purification and characterisation of the C
      terminal 89 amino acids of the protein encompassing the DNA binding/dimerisation
      domain. We show that the recombinant protein purified from E.coli by a
      combination of non-group-specific chromatography steps retains high biological
      activity and is able to bind to all sites in the HPV-16 genome with high affinity
      (approximately 8 x 10(-11) M). In addition, kinetic studies show that the E2-DNA
      complexes are very stable, with half-lives ranging from 2.15 to greater than 240
      min, and that nucleotides internal and external to the conserved palindrome
      appear to influence stability.

PMID- 7800478
TI  - Two silencing sub-domains of v-erbA synergize with each other, but not with RXR.
AB  - The thyroid hormone receptor (TR) and the retinoic acid receptor (RAR) induce
      gene expression in the presence of specific ligand and repress transcription in
      the absence of hormone. This repression is mediated by an active silencing
      mechanism rather then by interference with DNA binding activators. V-erbA, a
      variant form of TR which is unable to bind hormone, represents a constitutive
      repressor. Here we show, using fusion proteins with the GAL4 DNA binding domain,
      that the minimal silencing domain of v-erbA extends from amino acids 389 to 632
      and that internal deletions within this domain retain at least some repression
      function. Co-transfection experiments of different deletion mutants indicate that
      the silencing domain is composed of at least two sub-domains which are non
      functional when tested individually. When combined in a heterodimeric complex,
      they synergize such that silencing activity is regained. In contrast to the
      retinoic acid receptor the retinoid X receptor does not contain a silencing
      domain. In addition it is unable to cooperate with the repression function of TR
      or v-erbA in a heterodimer.

PMID- 7800479
TI  - Isolation and characterization of two Saccharomyces cerevisiae genes that encode
      proteins that bind to (TG1-3)n single strand telomeric DNA in vitro.
AB  - By screening lambda gt11 libraries with a radiolabeled (TG1-3)n oligonucleotide,
      two Saccharomyces cerevisiae genes were identified that encode polypeptides that
      recognize the single-stranded telomeric repeat sequence (TG1-3)n. The first gene,
      NSR1, a previously identified gene, encodes a protein involved in ribosomal RNA
      maturation and possibly in transport of proteins into the nucleus. The second
      gene, GBP2 (G-strand Binding Protein), is an anonymous open reading frame from
      chromosome III. These two genes contain RNA recognition motifs (RRMs) that are
      found in proteins that interact with RNA. Both Nsr1p and Gbp2p bind specifically
      to yeast single strand (TG1-3)n DNA in vitro. To test whether these two proteins
      associate with telomeres in vivo, strains were constructed in which one or both
      of these genes were either disrupted or overexpressed. None of these alterations
      affected telomere length or telomere position effect. The potential role of these
      two (TG1-3)n binding proteins is discussed.

PMID- 7800480
TI  - Different members of the Sp1 multigene family exert opposite transcriptional
      regulation of the long terminal repeat of HIV-1.
AB  - Recently, a family of transcription factors structurally related to Sp1 has been
      described; thus, more than one activator may bind to the GC boxes present in a
      number of viral and cellular promoters. We have compared the transactivation
      potentials of Sp1, Sp3 and Sp4 proteins on the human immunodeficiency virus type
      1 (HIV-1) promoter. The long terminal repeat (LTR) of HIV-1 contains three
      binding sites for the transcription factor Sp1 (GC boxes) which are involved in
      both basal and Tat-mediated transcriptional activation. Moreover, a cooperative
      interaction between NF-kappa B and Sp1 is required for HIV enhancer activation.
      We now demonstrate that Sp4 is an activator, while the Sp3 protein represses
      basal expression of HIV promoter. Remarkably, we found that over-expression of
      the transcription factor Sp3 was able to suppress Tat-mediated transactivation.
      These inhibitory effects of Sp3 correlate with its DNA binding activity,
      suggesting that Sp3 inhibition involves competition with Sp1 for occupancy of the
      GC boxes. Next, we have analyzed the role of different Sp1-related proteins in
      the stimulation of HIV-1 promoter in response to mitogens. We found that the
      binding of NF-kappa B is not by itself sufficient to induce HIV gene expression.
      Instead, an interaction between NF-kappa B and the trans-acting domain (A domain)
      of Sp1 bound to an adjacent site must occur. We found that the cooperative
      interaction between NF-kappa B and Sp1 is highly specific, since neither Sp3 nor
      Sp4 is capable of cooperating with NF-kappa B.

PMID- 7800481
TI  - Construction and characterization of a bacterial artificial chromosome library of
      Sorghum bicolor.
AB  - The construction of representative large insert DNA libraries is critical for the
      analysis of complex genomes. The predominant vector system for such work is the
      yeast artificial chromosome (YAC) system. Despite the success of YACs, many
      problems have been described including: chimerism, tedious steps in library
      construction and low yields of YAC insert DNA. Recently a new E.coli based system
      has been developed, the bacterial artificial chromosome (BAC) system, which
      offers many potential advantages over YACs. We tested the BAC system in plants by
      constructing an ordered 13,440 clone sorghum BAC library. The library has a
      combined average insert size, from single and double size selections, of 157 kb.
      Sorghum inserts of up to 315 kb were isolated and shown to be stable when grown
      for over 100 generations in liquid media. No chimeric clones were detected as
      determined by fluorescence in situ hybridization of ten BAC clones to metaphase
      and interphase S.bicolor nuclei. The library was screened with six sorghum probes
      and three maize probes and all but one sorghum probe hybridized to at least one
      BAC clone in the library. To facilitate chromosome walking with the BAC system,
      methods were developed to isolate the proximal ends of restriction fragments
      inserted into the BAC vector and used to isolate both the left and right ends of
      six randomly selected BAC clones. These results demonstrate that the S. bicolor
      BAC library will be useful for several physical mapping and map-based cloning
      applications not only in sorghum but other related cereal genomes, such as maize.
      Furthermore, we conclude that the BAC system is suitable for most large genome
      applications, is more 'user friendly' than the YAC system, and will likely lead
      to rapid progress in cloning biologically significant genes from plants.

PMID- 7800482
TI  - Role of a small RNA pol II subunit in TATA to transcription start site spacing.
AB  - The yeast shi mutation affects the spacing between the TATA promoter element and
      transcription initiation sites; for the H2B and ADH1 genes, a series of start
      sites located approximately 50-80 bp downstream of TATA is used in addition to
      the wild-type initiation sites located at around 100 bp from TATA (1). Here, the
      yeast SHI wild-type gene has been isolated by complementation and shown to be
      identical to RPB9, the gene encoding a small subunit of RNA polymerase II. A
      point mutation in the shi gene, changing a cysteine residue in a putative zinc
      ribbon motif into a phenylalanine residue, was demonstrated to permit the
      observed usage of upstream initiation sites. Deletion of the non-essential SHI
      gene also results in usage of upstream initiation sites and causes conditional
      growth defects.

PMID- 7800483
TI  - Properties of damage-dependent DNA incision by nucleotide excision repair in
      human cell-free extracts.
AB  - Nucleotide excision repair (NER) is the primary mechanism for the removal of many
      lesions from DNA. This repair process can be broadly divided in two stages:
      first, incision at damaged sites and second, synthesis of new DNA to replace the
      oligonucleotide removed by excision. In order to dissect the repair mechanism, we
      have recently devised a method to analyze the incision reaction in vitro in the
      absence of repair synthesis (1). Damage-specific incisions take place in a repair
      reaction in which mammalian cell-free extracts are mixed with undamaged and
      damaged plasmids. Most of the incision events are accompanied by excision. Using
      this assay, we investigated here various parameters that specifically affect the
      level of damage-dependent incision activity by cell-free extracts in vitro. We
      have defined optimal conditions for the reaction and determined the kinetics of
      the incision with cell-free extracts from human cells. We present direct evidence
      that the incision step of NER is ATP-dependent. In addition, we observe that Mn2+
      but no other divalent cation can substitute for Mg2+ in the incision reaction.

PMID- 7800484
TI  - Expression of the E. coli fpg gene in mammalian cells reduces the mutagenicity of
      gamma-rays.
AB  - The E. coli fpg gene encodes the formamido-pyrimidine-DNA-glycosylase (FPG
      protein) which specifically removes the formamido-pyrimidine and C8-oxoGuanine
      residues from gamma-irradiated DNA. The fpg gene was ligated in the psV2 vector
      and transfected into the Chinese hamster CHO and V-79 cells. The transfected
      cells expressed a formamido-pyrimidine-DNA-glycosylase activity 30 to 40-fold
      over the constitutive level. The resistance of CHO and V-79 cells to the lethal
      effect of gamma-rays was similar in control and transfected cells. Furthermore
      CHO cells expressing the fpg gene had the same resistance to the lethal effect of
      hydrogen peroxide as control cells. However, the sensitivity to the mutagenic
      effect of gamma-rays, measured as 6-thioguanine resistance, decreased both in CHO
      and V-79 transfected cells. Since the lethal effect of gamma-rays was not
      modified in cells overproducing the FPG protein, the results suggest that this
      protein protects the cells against the mutagenic lesions formed by ionizing
      radiations, and among them C8-oxoguanine.

PMID- 7800485
TI  - An RNA-protein contact determined by 5-bromouridine substitution,
      photocrosslinking and sequencing.
AB  - An analogue of the replicase translational operator of bacteriophage R17, that
      contains a 5-bromouridine at position -5 (RNA 1), complexes with a dimer of the
      coat protein and photocrosslinks to the coat protein in high yield upon
      excitation at 308 nm with a xenon chloride excimer laser. Tryptic digestion of
      the crosslinked nucleoprotein complex followed by Edman degradation of the
      tryptic fragment bearing the RNA indicates crosslinking to tyrosine 85 of the
      coat protein. A control experiment with a Tyr 85 to Ser 85 variant coat protein
      showed binding but no photocrosslinking at saturating protein concentration. This
      is consistent with the observation from model compound studies of preferential
      photocrosslinking of BrU to the electron rich aromatic amino acids tryptophan,
      tyrosine, and histidine with 308 nm excitation.

PMID- 7800486
TI  - RNA polymerase II phosphorylation: uncoupling from GAL4-VP16 directed open
      complex formation and transcription in a reconstituted system.
AB  - An activated transcription system was constructed using substantially purified
      liver factors, Hela TFIID and GAL4-VP16. The system was used to study the
      relationship between RNA polymerase II large subunit phosphorylation and other
      ATP-dependent processes occurring during activated transcription. When C-terminal
      domain (CTD) kinase activity was inhibited, activator dependent open promoter
      complex formation proceeded normally. These open complexes could function to
      produce RNA in the absence of CTD phosphorylation, although the level of RNA
      produced was changed somewhat. The results demonstrate that RNA polymerase II CTD
      phosphorylation is not generally required for the formation of activator
      dependent, functional open promoter complexes. Taken together with prior results
      the experiments suggest that a requirement for CTD phosphorylation may be
      situation-dependent and thus serve a regulatory function.

PMID- 7800487
TI  - Translation of 2'-modified mRNA in vitro and in vivo.
AB  - 2'-Fluoro- and 2'-amino-2'-deoxynucleoside triphosphates have been used for in
      vitro transcription of 2'-modified luciferase mRNA. The 2'-modified
      deoxynucleoside-containing transcripts were tested for the expression of
      luciferase in X.Laevis oocytes as well as in rabbit reticulocyte lysate. Only 2'
      fluoro-2'-deoxy-adenosine-modified mRNA gave rise to luciferase as shown by SDS
      gel as well as by enzyme activity measurements in vivo as well as in vitro. 2'
      Fluoro-2'-deoxy-pyrimidine nucleoside-modified mRNA did not give rise to
      luciferase activity. However, they directed incorporation of 35S-labeled
      methionine into peptide fragments in rabbit reticulocyte lysate indicating
      premature termination of translation. No or only extremely little of such
      incorporation could be detected with 2'-amino modified transcripts.

PMID- 7800488
TI  - DNA binding specificity of the wheat bZIP protein EmBP-1.
AB  - EmBP-1 is a wheat DNA binding protein of the basic leucine zipper (bZIP) class of
      transcription factors implicated in the mechanisms of abscisic acid mediated gene
      activation. Understanding the role of EmBP-1 in regulating gene transcription
      requires elucidation of its DNA binding specificity. The binding of EmBP-1 was
      studied using gel shift selection of DNA from random sequence pools. DNA binding
      sites were identified by sequencing of a selected pool and by cloning and
      sequencing individual sites. The binding sites were compared by mobility shift
      assay and DNase I footprinting, which show that EmBP-1 binds to a family of
      sequences with varying degrees of affinity. The highest affinity site bound by
      EmBP-1 is the palindrome GCCACGTGGC. EmBP-1 also binds several other sequences
      with high affinity, however most of these are asymmetric. While nearly all
      sequences bound by EmBP-1 contain an ACGT core sequence, EmBP-1 can also bind at
      least two sites with altered cores. These results provide a basis for comparing
      the DNA binding specificity of EmBP-1 with those of other plant bZIP proteins and
      provide insight into the possible target sites which EmBP-1 might bind in vivo.

PMID- 7800489
TI  - Sequence-specific DNA double-strand breaks induced by triplex forming 125I
      labeled oligonucleotides.
AB  - A triplex-forming oligonucleotide (TFO) complementary to the polypurine
      polypyrimidine region of the nef gene of the Human Immunodeficiency Virus (HIV)
      was labeled with 125I at the C5 position of a single deoxycytosine residue.
      Labeled TFO was incubated with a plasmid containing a fragment of the nef gene.
      Decay of 125I was found to cause double-strand breaks (DSB) within the nef gene
      upon triplex formation in a sequence specific manner. No DSB were detected after
      incubation at ionic conditions preventing triplex formation or when TFO was
      labeled with 32P instead of 125I. Mapping DSB sites with single base resolution
      showed that they are distributed within 10 bp of a maximum located exactly
      opposite the position of the [125I] IdC in the TFO. We estimate that on average
      the amount of DSB produced per decay is close to one.

PMID- 7800490
TI  - The pseudodisaccharides: a novel class of group I intron splicing inhibitors.
AB  - Lysinomicin, a naturally-occurring pseudodisaccharide, inhibits translation in
      prokaryotes. We report that lysinomicin (and three related compounds) are able to
      inhibit the self-splicing of group I introns, thus identifying
      pseudodisaccharides as a novel class of group I intron splicing inhibitors.
      Lysinomicin inhibited the self-splicing of the sunY intron of phage T4 with a Ki
      of 8.5 microM (+/- 5 microM) and was active against other group I introns.
      Inhibition was found to be competitive with the substrate guanosine, unlike
      aminoglycoside antibiotics, which act non-competitively to inhibit the splicing
      of group I introns. Competitive inhibitors of group I intron splicing known to
      date all contain a guanidino group that was thought to be required for
      inhibition; lysinomicin lacks a guanidino group.

PMID- 7800491
TI  - Replication initiation sites are distributed widely in the amplified CHO
      dihydrofolate reductase domain.
AB  - In previous studies, we utilized a neutral/neutral two-dimensional (2-D) gel
      replicon mapping method to analyze the pattern of DNA synthesis in the amplified
      dihydrofolate reductase (DHFR) domain of CHOC 400 cells. Replication forks
      appeared to initiate at any of a large number of sites scattered throughout the
      55 kb region lysing between the DHFR and 2BE2121 genes, and subsequently to move
      outward through the two genes. In the present study, we have analyzed this locus
      in detail by a complementary, neutral/alkaline 2-D gel technique that determines
      the direction in which replication forks move through a region of interest. In
      the early S period, forks are observed to travel in both directions through the
      intergenic region, but only outward through the DHFR gene. Surprisingly, however,
      replication forks also move in both directions through the 2BE2121 gene.
      Furthermore, in early S phase, small numbers of replication bubbles can be
      detected in the 2BE2121 gene on neutral/neutral 2-D gels. In contrast,
      replication bubbles have never been detected in the DHFR gene. Thus, replication
      initiates not only in the intergenic region, but also at a lower frequency in the
      2BE2121 gene. We further show that only a small fraction of DHFR amplicons
      sustains an active initiation event, with the rest being replicated passively by
      forks from distant amplicons. These findings are discussed in light of other
      experimental approaches that suggest the presence of a much more narrowly
      circumscribed initiation zone within the intergenic region.

PMID- 7800492
TI  - Mechanistic studies on depurination and apurinic site chain breakage in
      oligodeoxyribonucleotides.
AB  - Products formed from defined oligodeoxyribonucleotide tetramers
      (oligonucleotides) by depurination at pH 5.0 and 90 degrees C followed by chain
      breakage at the resulting apurinic sites (AP sites) were assigned by reversed
      phase HPLC. Through kinetic analysis, rate constants of depurination and
      subsequent chain breakage reactions were measured. Depurination of the
      oligonucleotides with purine bases locating at the terminal positions was several
      times faster than those with purines at the internal ones. The pKa values for the
      N7 of the G residues and the activation energies of the depurination were
      essentially independent of the position of the bases. The frequency factor was
      found to be responsible for the observed difference of the depurination rates. In
      contrast, the chain breakage by beta-elimination was several times faster for the
      AP sites formed at the internal positions than those at the 5'-terminal
      positions. It is suggested that an electron withdrawing phosphate group attached
      to the 5'-side of an AP site facilitates the chain cleavage.

PMID- 7800493
TI  - Introduction of YACs into intact yeast cells by a procedure which shows low
      levels of recombinagenicity and co-transformation.
AB  - Yeast artificial chromosomes (YACs) enable the cloning and analysis of large
      segments of genomic DNA and permit the isolation of sequences which are
      impossible to maintain in Escherichia coli. However, the construction of genome
      libraries in YAC vectors is beset by a number of technical problems, not least of
      which is the creation of cloned fragments which are not true representatives of
      the donor genome. These artefactual clones arise mainly due to intra-fragment
      rearrangements or inter-fragment chimaera formation, both phenomena resulting
      from the activity of the host yeast's mitotic recombination system. We
      demonstrate that this system is significantly stimulated by the spheroplasting
      step of the standard YAC transformation system. In contrast, the transformation
      of intact yeast cells by either the lithium method or a new lithium-free protocol
      is much less recombinagenic. It is not possible to introduce high molecular
      weight YACs into yeast using the lithium protocol, but we find that such
      molecules may be introduced into pde2-mutants using the lithium-free approach.
      Since intact cells are transformed by this method, automation of post
      transformation steps in the construction of YAC libraries is facilitated.
      Moreover, the frequency of cotransformation (and, therefore, chimera formation)
      is significantly reduced. However, these advantages do incur a penalty. Yields of
      YAC transformants by this simplified intact cell approach are reduced some 25- to
      30-fold compared to those obtained by the spheroplast transformation route.
      Nevertheless, the considerable advantages of the new system recommend it for a
      number of applications.

PMID- 7800494
TI  - Transcriptional induction of the mouse metallothionein-I gene in hydrogen
      peroxide-treated Hepa cells involves a composite major late transcription
      factor/antioxidant response element and metal response promoter elements.
AB  - Synthesis of metallothionein-I (MT-I) and heme oxygenase mRNAs is rapidly and
      transiently induced by H2O2 in mouse hepatoma cells (Hepa) and this effect is
      blocked by catalase. Menadione, which generates free radicals, also induces these
      mRNAs. Deletion mutagenesis revealed that a region between -42 and -153 in the
      mouse MT-I promoter was essential for induction of a CAT reporter gene. A
      multimer of a 16 bp sequence (-101 to -86) that includes an antioxidant response
      element and overlapping adenovirus major late transcription factor binding site
      elevated basal expression and allowed induction by H2O2 when inserted upstream of
      a minimal promoter. However, deletion of this region (-100 to -89) from the
      intact MT-I promoter (-153) did not completely eliminate response. Multiple
      copies of a metal response element also permitted response to H2O2. These results
      suggest that induction of MT-I gene transcription by H2O2 is mediated by at least
      two different elements within the proximal MT-I gene promoter and suggest a
      previously undescribed function of the MRE. Induction of MT gene transcription by
      ROS and the subsequent scavenging of ROS by the MT peptide is reminiscent of the
      metal regulatory loop and is consistent with the hypothesized protective
      functions of MT.

PMID- 7800495
TI  - CD and DNA binding studies of a proline repeat-containing segment of the
      replication arrest protein Tus.
AB  - Tus is a sequence-specific DNA binding protein that regulates its own
      transcription and can arrest Escherichia coli replication when bound to Ter sites
      on the chromosome. In order to identify segments of Tus that may be involved in
      DNA binding interactions we have analyzed the Tus amino acid sequence with
      respect to secondary structure motifs and similarity to other protein sequences.
      A twenty amino acid segment containing several basic residues and a proline
      repeat motif with a periodicity of five residues was identified. The motif was
      common to several other nucleic acid binding proteins, including histone H1-3,
      Xenopus laevis ribosomal protein L1, and the single-stranded DNA binding protein
      (DBP) from adenovirus. A 22 amino acid peptide, TPPI, having a sequence similar
      to the Tus segment binds non-specifically and non-cooperatively to double- and
      single-stranded DNA with a binding constant of 1.5 +/- 0.2 x 10(6) M-1. The
      estimated binding site size was 4.3 +/- 0.5 base pairs. Circular dichroism
      studies indicated that the peptide was a random coil in buffer but adopted a
      helical structure in 50% trifluroethanol and in sodium dodecyl sulfate at
      concentrations above the critical micellar concentration. Several helical models
      of the TPPI sequence were constructed graphically and minimized. One of them, an
      amphiphilic, left-handed, 5.1(19) helical model was best able to account for the
      observed structural properties of TPPI in the presence of structure-promoting
      additives.

PMID- 7800496
TI  - Histidylation by yeast HisRS of tRNA or tRNA-like structure relies on residues -1
      and 73 but is dependent on the RNA context.
AB  - Residue G-1 and discriminator base C73 are the major histidine identity elements
      in prokaryotes. Here we evaluate the importance of these two nucleotides in yeast
      histidine aminoacylation identity. Deletion of G-1 in yeast tRNA(His) transcript
      leads to a drastic loss of histidylation specificity (about 500-fold). Mutation
      of discriminator base A73, common to all yeast tRNA(His) species, into G73 has a
      more moderate but still significant effect with a 22-fold decrease in
      histidylation specificity. Changes at position 36 in the anticodon loop has
      negligible effect on histidylation. The role of residues -1 and 73 for specific
      aminoacylation by yeast HisRS was further investigated by studying the
      histidylation capacities of seven minihelices derived from the Turnip Yellow
      Mosaic Virus tRNA-like structure. Changes in the nature of nucleotides -1 and 73
      modulate this activity but do not suppress it. The optimal mini-substrate for
      HisRS presents a G.A mismatch at the position equivalent to residues G-1.A73 in
      yeast tRNA(His), confirms the importance of this structural feature in yeast
      histidine identity. The fact that the minisubstrates contain a pseudoknot in
      which position -1 is mimicked by an internal nucleotide from the pseudoknot
      highlights further the necessity of a stacking interaction of this position over
      the amino acid accepting branch of the tRNA during the aminoacylation process.
      Individual transplantation of G-1 or A73 into yeast tRNA(Asp) transcript improves
      the histidylation efficiency of the engineered tRNA(Asp). However, a tRNA(Asp)
      transcript presenting simultaneously both residues G-1 and A73 becomes a less
      good substrate for HisRS, suggesting the importance of the structural context
      and/or the presence of antideterminants for an optimal expression of these two
      identity elements.

PMID- 7800497
TI  - Replication fork barriers in the Xenopus rDNA.
AB  - To investigate replication fork progression along the tandemly repeated rRNA
      genes of Xenopus laevis and Xenopus borealis, rDNA replication intermediates from
      dividing tissue culture cells were analyzed by two-dimensional gel
      electrophoresis. Analysis of the direction of replication in the rRNA coding
      regions revealed replication forks moving in both directions. However, in both
      frog species, polar replication fork barriers (RFB) arresting forks approaching
      the rRNA transcription units from downstream were identified. Whereas in X.
      borealis the RFB maps to a defined site close to the transcription terminator, in
      X. laevis the arrest of fork movement can occur at multiple positions throughout
      a 3' flanking repetitive spacer region. A short DNA element located near the
      respective RFB sites is shared between these two related frog species, suggesting
      its possible involvement in the arrest of replication fork movement. In a subset
      of rDNA repeats, these barriers cause an absolute block to replication fork
      progression, defining the sites where replicon fusion occurs, whereas in the
      remainder repeats, most probably in the non-transcribed gene copies, the
      replication machinery can pass the RFB sequences and replicate the rRNA
      transcription unit in a 3'-to-5' direction.

PMID- 7800498
TI  - Regulation of influenza virus RNA polymerase activity by cellular and viral
      factors.
AB  - An in vitro RNA synthesis system mimicking replication of genomic influenza virus
      RNA was developed with nuclear extracts prepared from influenza virus-infected
      HeLa cells using exogenously added RNA templates. The RNA synthesizing activity
      was divided into two complementing fractions, i.e. the ribonucleoprotein (RNP)
      complexes and the fraction free of RNP, which could be replaced with RNP cores
      isolated from virions and nuclear extracts from uninfected cells, respectively.
      When nuclear extracts from uninfected cells were fractionated by phosphocellulose
      column chromatography, the stimulatory activity for RNA synthesis was further
      separated into two distinct fractions. One of them, tentatively designated RAF
      (RNA polymerase activating factor), stimulated RNA synthesis with either RNP
      cores or RNA polymerase and nucleocapsid protein purified from RNP cores as the
      enzyme source. In contrast, the other, designated PRF (polymerase regulating
      factor), functioned as an activator only when RNP cores were used as the enzyme
      source. Biochemical analyses revealed that PRF facilitates dissociation of RNA
      polymerase from RNP cores. Of interest is that virus-coded non-structural protein
      1 (NS1), which has been thought to be involved in regulation of replication,
      counteracted PRF function. Roles of cellular factors and viral proteins, NS1 in
      particular, are discussed in terms of regulation of influenza virus RNA genome
      replication.

PMID- 7800499
TI  - Molecular sequestration stabilizes CAP-DNA complexes during polyacrylamide gel
      electrophoresis.
AB  - The gel electrophoresis mobility shift assay is widely used for qualitative and
      quantitative characterization of protein complexes with nucleic acids. Often it
      is found that complexes that are short-lived in free solution (t1/2 of the order
      of minutes) persist for hours under the conditions of gel electrophoresis. We
      have investigated the influence of polyacrylamide gels on the pseudo first-order
      dissociation kinetics of complexes containing the E.coli cyclic AMP receptor
      protein (CAP) and lactose promoter DNA. Within the gel matrix, kdiss decreased
      with increasing [polyacrylamide] and the order of the reaction was changed. In
      free solution, kdiss was proportional to [DNA]2, while in 5% gels, kdiss was
      proportional to [DNA]0.3. In gels of [polyacrylamide] > or = 10%, kdiss was
      nearly independent of [DNA] until fragment concentrations exceeded 0.1 microM.
      Even in the absence of competing DNA, kdiss(gel) < kdiss(solution). These results
      suggest that the lifetime of CAP-DNA complexes in free solution is limited by
      their encounter frequency with molecules of DNA or with protein-DNA complexes;
      some or all of the stabilization observed in gels may be due to a reduction in
      this frequency.

PMID- 7800500
TI  - A multifunctional expression vector for an anti-HIV-1 ribozyme that produces a 5'
      and 3'-trimmed trans-acting ribozyme, targeted against HIV-1 RNA, and cis-acting
      ribozymes that are designed to bind to and thereby sequester trans-activator
      proteins such as Tat and Rev.
AB  - We previously constructed a multiribozyme expression vector by combining cis- and
      trans-acting ribozymes and we showed that several ribozymes, each directed
      against a different target in the HIV genome and acting independently in a
      'shotgun' manner, markedly increased the efficiency of cleavage of HIV RNA in
      vitro [Ohkawa et al., Proc. Natl Acad. Sci. USA 90, 11302 (1993)]. However, the
      cis-acting ribozymes that had trimmed the 5' and 3' ends of each trans-acting
      ribozyme were designed merely to await for degradation by RNases when they were
      used in vivo. Since several trans-activator proteins are essential for viral
      replication of HIV-1, we wondered whether a decoy function could be coupled with
      the cleavage activity of ribozymes. We therefore introduced the TAR or the RRE
      sequence into the stem II region of each cis-acting ribozyme. When the activity
      of each resulting cis-acting ribozyme that had been endowed with the decoy
      function was examined in vitro, it was found to retain almost full trimming
      activity. Moreover, cis-acting ribozymes with either the TAR or the RRE sequence
      were shown to be able to trap Tat or Rev protein successfully. It is, therefore,
      possible to endow the stem II region with a specific protein-binding function
      without the loss of ribozyme function. Thus, cis-acting ribozymes, endowed with
      the decoy function, can first trim the 5' and 3' ends of each trans-acting
      ribozyme and are then still available for trapping trans-activator proteins
      possibly prior to their degradation by RNases when they are to be used in vivo.
      Furthermore, it is also expected that the reduction in production of HIV RNA that
      is achieved by sequestering the trans-activator proteins might provide the trans
      acting ribozymes, targeted to HIV RNA, with a better chance of eliminating the
      remaining HIV RNA.

PMID- 7800501
TI  - Unusual properties of genomic DNA molecules spanning the euchromatic
      heterochromatic junction of a Drosophila minichromosome.
AB  - While investigating the copy number of minichromosome Dp(1;f)1187 sequences in
      the polyploid chromosomes of ovarian nurse and follicle cells of Drosophila
      melanogaster we discovered that restriction fragments spanning the euchromatic
      heterochromatic junction of the chromosome and extending into peri-centromeric
      sequences had the unusual property of being selectively resistant to transfer out
      of agarose gels during Southern blotting, leading to systematic reductions in
      Dp1187-specific hybridization signals. This property originated from the peri
      centromeric sequences contained on the junction fragments and was persistently
      associated with Dp1187 DNA, despite attempts to ameliorate the effect by altering
      experimental protocols. Transfer inhibition was unlikely to be caused by an
      inherent physical property of repetitive DNA sequences since, in contrast to
      genomic DNA, cloned restriction fragments spanning the euchromatic
      heterochromatic junction and containing repetitive sequences transferred
      normally. Finally, the degree of inhibition could be suppressed by the addition
      of a Y chromosome to the genotype. On the basis of these observations and the
      fact that peri-centromeric regions of most eukaryotic chromosomes are associated
      with cytologically and genetically defined heterochromatin, we propose that peri
      centromeric sequences of Dp1187 that are incorporated into heterochromatin in
      vivo retain some component of heterochromatic structure during DNA isolation,
      perhaps a tightly bound protein or DNA modification, which subsequently causes
      the unorthodox properties observed in vitro.

PMID- 7800502
TI  - Selective chemical autoligation on a double-stranded DNA template.
AB  - We show that a double-stranded DNA segment serves as an effective template for
      spontaneously coupling short pyrimidine oligonucleotides containing terminal 
      P(O)(O-)S- and BrCH2C(O)NH- groups. The efficiency of this autoligation depends
      markedly on proper base-pairing between the probe oligomers and the double
      stranded target. This chemistry should be useful in designing highly selective
      probes for double-stranded polynucleotide segments.

PMID- 7800503
TI  - Analysis of the micronuclear B type surface protein gene in Paramecium
      tetraurelia.
AB  - The micronuclear DNA of Paramecium contains sequences that are precisely excised
      during the formation of the macronuclear (somatic) genome. In this paper we show
      that four eliminated sequences ranging in size from 28 to 416 base pairs, are
      present in or near the micronuclear copy of the B surface protein gene. Each
      excised sequence is bounded by the dinucleotide 5'-TdA-3'. Comparison of the
      micronuclear B gene with the previously determined micronuclear sequence of the A
      surface protein gene shows that although the positions of at least three of the
      eliminated sequences are conserved in both genes, the sequences are highly
      divergent. Transformation of vegetative macronuclei with fragments of the
      micronuclear B gene results in replication and maintenance of the DNA, but the
      micronuclear specific sequences are not removed. Previous studies have shown that
      the correct incorporation of the B gene into the new macronucleus requires copies
      of the macronuclear B gene in the old macronucleus. Using macronuclear
      transformation, we show that the micronuclear B gene can substitute for the
      macronuclear B gene with regard to its role in DNA processing. This suggests that
      the macronuclear DNA is not acting as a guide for the excision of the
      micronuclear specific sequences.

PMID- 7800504
TI  - Novel clustering of Sp1 transcription factor binding sites at the transcription
      initiation site of the human muscle phosphofructokinase P1 promoter.
AB  - The regulatory sequence elements of the human muscle phosphofructokinase (HPFKM)
      p1 promoter from -655 to +78 were cloned and characterized. In the human cervical
      carcinoma cell line, HeLa S3, the HPFKM type C RNA initiated from a single
      predominant transcription initiation site and the HPFKM p1 promoter displayed
      transcriptional activity in transient transfection assays. The HPFKM p1 promoter
      region was shown to possess eight binding sites for the Sp1 transcription factor
      by DNase I footprinting and gel retardation analysis. The functional importance
      of these interactions was examined by transient transfection analysis in
      Drosophila SL2 and HeLa S3 cells. This analysis demonstrated that the HPFKM p1
      promoter sequence between +12 and +78 retained Sp1-dependent transcriptional
      activity in Drosophila SL2 cells and retained promoter activity in HeLa S3 cells.
      These results suggest that the Sp1 binding site (site 8 between +12 and +21)
      immediately adjacent to the transcription initiation site represents an important
      regulatory element of this promoter at least in the context of the minimal HPFKM
      p1 promoter. However mutagenesis of the Sp1 site 8 demonstrated that, in the
      context of a larger HPFKM p1 promoter region containing Sp1 sites 1 to 7, it now
      contributed very little to the total promoter activity. Therefore it appears the
      Sp1 sites in the HPFKM p1 promoter display functional redundancy.

PMID- 7800505
TI  - Characterization of the promoter for the human 85 kDa cytosolic phospholipase A2
      gene.
AB  - The 85 kDa cytosolic phospholipase A2 (cPLA2) plays a key role in the production
      of arachidonic acid and lysophospholipids, the precursors of eicosanoids and
      platelet-activating factor. Here we report the cloning of the promoter of the
      human cPLA2 gene. A 5.7 kb EcoRI fragment containing the most 5' region of the
      cPLA2 cDNA was sequenced. The transcription initiation site was identified by
      rapid amplification of 5'-cDNA ends (5'-RACE) and primer extension analysis. DNA
      sequence analysis of the 595 base pairs 5' of the transcription start site
      reveals a 48 base purine-pyrimidine dinucleotide repeat (CA repeat), five
      interferon-gamma response elements (gamma-IRE), one interferon-gamma activated
      sequence (GAS) and two glucocorticoid response elements (GRE). The promoter lacks
      a TATA box. It contains a possible CAAT box at -111 and two octamer binding
      motifs. The 595 base fragment located immediately upstream of the transcriptional
      start site exhibited functional promoter activity in transient transfection
      assays in a bronchial epithelial cell line (BEAS 2B cells). Deletion analysis
      revealed that the CA repeat may confer an inhibitory effect on the cPLA2 promoter
      activity. The characterization of the human cPLA2 promoter sequence will allow
      further studies defining the molecular events regulating the expression of the
      cPLA2 enzyme, especially the cytokine mediated cPLA2 gene expression.

PMID- 7800506
TI  - Identification and characterization of multiple A/T-rich cis-acting elements that
      control expression from Dictyostelium actin promoters: the Dictyostelium actin
      upstream activating sequence confers growth phase expression and has enhancer
      like properties.
AB  - The promoter elements in the Dictyostelium actin 15 and actin 6 genes required
      for full growth phase expression were identified by assaying promoter/luciferase
      reporter constructs. We find that these promoters contain common cis-acting
      elements, an actin upstream activating sequence (UAS) and sequences proximal to
      the transcription start site that overlap with a poly(dT) region. The actin 15
      promoter has two additional cis-acting elements not present in the actin 6
      promoter that may account for the higher level of expression from the actin 15
      promoter. All of the identified promoter elements are unusual for Dictyostelium
      in that they are all A/T-rich. Two cis-acting elements, the actin UAS and the
      poly(dT) domain were studied in greater detail. The actin UAS was tested on a
      heterologous promoter from the prespore-specific gene SP60 and shown to have the
      ability to confer growth phase expression. The actin UAS also exhibited the
      ability to function in a distance- and orientation-independent manner and
      activate expression synergistically when present in two copies. The poly(dT)
      domain of the actin 15 promoter was studied in greater detail by using a genetic
      selection scheme to define parameters that effect the strength of this element.
      This element is comprised of 45 consecutive dT residues immediately upstream of
      the putative TATA box. We show that the length of the homopolymer dT region
      correlates with the expression level of the promoter. The poly(dT) element is
      also shown to function to promote wild-type levels of expression with small
      deviations in the sequence, indicating that the element is not required to be
      homopolymeric to function.

PMID- 7800507
TI  - Stochastic context-free grammars for tRNA modeling.
AB  - Stochastic context-free grammars (SCFGs) are applied to the problems of folding,
      aligning and modeling families of tRNA sequences. SCFGs capture the sequences'
      common primary and secondary structure and generalize the hidden Markov models
      (HMMs) used in related work on protein and DNA. Results show that after having
      been trained on as few as 20 tRNA sequences from only two tRNA subfamilies
      (mitochondrial and cytoplasmic), the model can discern general tRNA from similar
      length RNA sequences of other kinds, can find secondary structure of new tRNA
      sequences, and can produce multiple alignments of large sets of tRNA sequences.
      Our results suggest potential improvements in the alignments of the D- and T
      domains in some mitochondrial tRNAs that cannot be fit into the canonical
      secondary structure.

PMID- 7800508
TI  - Alu repeated DNAs are differentially methylated in primate germ cells.
AB  - A significant fraction of Alu repeats in human sperm DNA, previously found to be
      unmethylated, is nearly completely methylated in DNA from many somatic tissues. A
      similar fraction of unmethylated Alus is observed here in sperm DNA from rhesus
      monkey. However, Alus are almost completely methylated at the restriction sites
      tested in monkey follicular oocyte DNA. The Alu methylation patterns in mature
      male and female monkey germ cells are consistent with Alu methylation in human
      germ cell tumors. Alu sequences are hypomethylated in seminoma DNAs and more
      methylated in a human ovarian dysgerminoma. These results contrast with
      methylation patterns reported for germ cell single-copy, CpG island, satellite,
      and L1 sequences. The function of Alu repeats is not known, but differential
      methylation of Alu repeats in the male and female germ lines suggests that they
      may serve as markers for genomic imprinting or in maintaining differences in male
      and female meiosis.

PMID- 7800510
TI  - Rapid isolation of DNA sequences flanking microsatellite repeats.

PMID- 7800509
TI  - Conformation, hydrogen bonding and aggregate formation of guanosine 5'
      monophosphate and guanosine in dimethylsulfoxide.
AB  - The tetrabutylammonium salt of guanosine 5'-monophosphate (5'-GMP) dissolves in
      DMSO-d6 forming aggregated species which exhibit some properties of reverse
      micelles. 1H NOESY experiments show that the 5'-GMP adopts the syn conformation
      about the glycosidic bond. Molecular mechanics calculations reveal a stable
      structure with this conformation in which the phosphate group and the amino group
      of the base are in close enough proximity to hydrogen bond. In contrast inosine
      5'-monophosphate in DMSO-d6, which has no NH2 group for hydrogen bond
      stabilization of the syn conformation, is shown by NMR to have the anti
      structure. Guanosine in DMSO-d6 behaves differently from 5'-GMP. Guanosine adopts
      the anti conformation and forms a symmetric dimer via hydrogen bonding between
      the N3 and NH2 of the bases.

PMID- 7800511
TI  - Are there two DNA methyltransferase gene families in plant cells? A new potential
      methyltransferase gene isolated from an Arabidopsis thaliana genomic library.

PMID- 7800513
TI  - Health farm. Interview by Phil Cohen.

PMID- 7800512
TI  - Mutational analysis of an essential binding site for the U3 snoRNA in the 5'
      external transcribed spacer of yeast pre-rRNA.
AB  - The small nucleolar RNA U3 is essential for viability in yeast. We have
      previously shown that U3 can be cross-linked in vivo to the pre-rRNA in the 5'
      external transcribed spacer (ETS), at +470. This ETS region contains 10
      nucleotides of perfect complementarity to U3. In a genetic background where the
      mutated rDNA is the only transcribed rDNA repeat, the deletion of the 10 nt
      complementary to U3 is lethal. Cells lacking the U3 complementary sequence in pre
      rRNA fail to accumulate 18S rRNA: pre-rRNA processing is inhibited at sites A0 in
      the 5' ETS, A1 at the 5' end of 18S rRNA and A2 in ITS1. We show here that
      effects on processing at site A0 are specific for U3 and its associated proteins
      and are not seen on depletion of other snoRNP components. The deletion of the
      sequence complementary to U3 in the ETS therefore mimics all the known effects of
      the depletion of U3 in trans. This indicates that we have identified an essential
      U3 binding site on pre-rRNA, required in cis for the maturation of 18S rRNA.

PMID- 7800514
TI  - A problem shared.

PMID- 7800515
TI  - Watching brief. Interview by Ian McMillan.

PMID- 7800516
TI  - An introduction to the examination of specimens.
AB  - This paper is the first of a series describing how laboratory examination of
      specimens contributes to the diagnosis and monitoring of disease. It offers a
      brief introduction to each of the disciplines within pathology, along with a
      general consideration of normal range, units of measurement and specimen
      collection.

PMID- 7800517
TI  - The significance of hand-drying in the prevention of infection.
AB  - The original research linking poor hand hygiene to the development of infection
      was conducted by Semmelweis over 100 years ago. His experiments have never been
      replicated in the hospital setting, but over the years powerful circumstantial
      evidence has accumulated to suggest that hands are the main vectors of micro
      organisms in both hospital and community and that hand-washing is the key to
      infection prevention. Nevertheless, many aspects of hand-washing remain under
      researched. The area that has received least attention is hand-drying, despite
      early suggestions that when a quick, perfunctory hand-wash is performed by busy
      nurses in the clinical situation, the mechanical action of drying contributes to
      the efficient removal of pathogens. This paper explores evidence to show that the
      use of paper towels is safer than hot air hand-dryers in busy wards.

PMID- 7800518
TI  - Are midwives ready for the proposals for change?
AB  - This paper analyses the results of a small study into what midwives feel about
      the specific proposals for changes to the delivery of maternity services as
      outlined in Changing Childbirth. The paper explores the important issues of
      midwives' attitudes to the proposed changes and how they view their current
      working situation. The author concludes from the survey that midwives need to
      reappraise their attitudes to women and childbirth, and that greater support from
      senior midwives is essential.

PMID- 7800519
TI  - Purchasing community nursing services.
AB  - Community nursing in the market place is much talked about. In this paper a
      purchaser of community nursing services outlines shifts in the focus of care
      locations and the necessary action community nurses need to take to respond to
      such change. The term 'community nursing' is used in this paper in its widest
      context to include district nursing, health visiting and the service provided by
      specialist nurses practising in the community, except where the different
      services are referred to specifically.

PMID- 7800521
TI  - Going it alone.

PMID- 7800520
TI  - Providing community nursing.

PMID- 7800522
TI  - Pain control. Controlled environment.

PMID- 7800523
TI  - Fear and loathing.

PMID- 7800524
TI  - It's a kind of magic.

PMID- 7800525
TI  - Ageing matters. Mores and morals.

PMID- 7800526
TI  - Ageing matters. Risk exposure.

PMID- 7800527
TI  - Professionals 'insensitive' to HIV women.

PMID- 7800528
TI  - Ahead of the field.

PMID- 7800529
TI  - Assisted places.

PMID- 7800530
TI  - Relative risk.

PMID- 7800531
TI  - The bursary blues.

PMID- 7800532
TI  - Semantic fiction.

PMID- 7800533
TI  - Health care assistants--the challenge for nursing staff.
AB  - One of the results of the introduction of Project 2000 has been the creation of a
      new type of support worker, the health care assistant (HCA). HCAs are
      increasingly being prepared for their role under the framework of the competence
      based National Vocational Qualification scheme, leading some observers to fear
      that this grade of staff could threaten the position of nurses in health-care
      teams.

PMID- 7800534
TI  - What can HCAs be asked to do?
AB  - Who should determine the role of health care assistants (HCAs)? If not nurses
      then managers may decide on the basis of cheapest is best. However, if nurses are
      to decide it is vital that they understand just what health care assistants can
      and cannot do.

PMID- 7800535
TI  - The Health Start initiative: a strategy to motivate staff.
AB  - The NHS is an organisation that spends the vast majority of its budget on people.
      This paper explains how one region demonstrated its commitment to invest in the
      health of its staff through a healthy initiatives scheme.

PMID- 7800536
TI  - Supporting staff health.
AB  - This paper continues the theme of health at work and explains how one company set
      in motion a corporate health promotion programme aimed at eliminating or reducing
      particular disease risk factors affecting the workforce.

PMID- 7800537
TI  - Reducing fast times in paediatric day surgery.
AB  - How easily can a nurse change established practice? By using audit to highlight
      the problem of prolonged fast times before elective day-case surgery for children
      and drawing on previous research performed on minimum fast times, this paper
      shows how nurse-led research can change established practice. The paper also
      shows that not all research is labour intensive, slow to show results and of only
      educative interest.

PMID- 7800538
TI  - Clinical supervision questionnaire results.
AB  - How do nurses know that they are practising in a safe, effective and
      professionally enriching way? And how or where do they get the professional
      support to develop their role when they need it, or the opportunity to share
      their expertise, to pass it on and expand the body of professional knowledge for
      the benefit of patient and client care? These questions were raised in an article
      on clinical supervision in Nursing Times on September 28. With the article was a
      questionnaire which invited readers to let the Department of Health, the UKCC and
      local policy-makers know how Nursing Times readers would like clinical
      supervision to be developed. Respondents were offered the opportunity to attend a
      major national conference to be held in November and one respondent would win a
      weekend for two at Ragdale Hall health farm, Leicestershire. This article briefly
      recaps the events which have led to clinical supervision being such an important
      and topical subject and discusses the results of the questionnaire.

PMID- 7800539
TI  - Enteral nutrition. From tube to table.

PMID- 7800540
TI  - A source of support.

PMID- 7800541
TI  - Midwives' Journal. Protecting the child.

PMID- 7800542
TI  - Midwives' Journal. Radical midwives' meeting.

PMID- 7800543
TI  - Midwives' Journal. Through a glass darkly.

PMID- 7800544
TI  - Nurses with HIV live in fear of disclosure.

PMID- 7800545
TI  - Unequal partners.

PMID- 7800546
TI  - No hiding place.

PMID- 7800547
TI  - Vanishing volunteers. Interview by Jane Cassidy.

PMID- 7800548
TI  - Fresh air.

PMID- 7800549
TI  - Caring for a patient with Huntington's disease.
AB  - This paper describes the nursing care of a 50-year-old woman with Huntington's
      disease. Orem's model was used to assess the patient and draw up an appropriate
      care plan. The difficulties involved in finding a suitable placement in a nursing
      home are also outlined.

PMID- 7800550
TI  - Welcoming patients--an underrated necessity.
AB  - This paper describes the use of a welcoming group for patients in an acute
      psychiatric ward for older people. The importance of welcoming is discussed are
      the practical elements involved.

PMID- 7800551
TI  - How health-care philosophies can be put into practice.
AB  - Four principal models of health have been identified. This paper explores these
      models from a practice-based perspective using as an example a woman who has had
      two strokes and who has dementia.

PMID- 7800552
TI  - Community service.

PMID- 7800553
TI  - Orthopaedic nursing. Collaboration course.

PMID- 7800554
TI  - Orthopaedic nursing. Liaising over care.

PMID- 7800556
TI  - Learning disabilities. Punishing interventions.

PMID- 7800555
TI  - Learning disabilities. Imbalance of power.

PMID- 7800557
TI  - Learning disabilities. Moral questions.

PMID- 7800558
TI  - Patient safety during radiofrequency catheter ablation: a clinical and regulatory
      dilemma.

PMID- 7800559
TI  - Atrial rate adaptive pacing: what happens to AV conduction?
AB  - To investigate if an nonphysiological prolongation of the AV interval is common
      during activity sensor modulated atrial rate adaptive (AAIR) pacing, 21 patients
      with sinus node disease treated with fixed rate atrial (AAI) or AAIR pacemakers
      were examined. Spike-Q intervals were compared at different heart rates obtained
      by overdrive pacing at rest and during exercise (Study I), measured during
      exercise at unresponsive (AAI), optimal (AAIR) and over responsive programming
      (AAIR+) of the activity sensor (Study II), and finally examined by 24-hour Holter
      recording in AAI and AAIR pacing modes (Study III). Study I: The spike-Q interval
      increased significantly with increasing heart rate at rest, but not during
      exercise. At rest the spike-Q interval was significantly higher at all heart
      rates compared to exercise. There was a significant positive correlation between
      the maximal spike-Q interval at rest and the maximal spike-Q interval during
      exercise (r = 0.63). Study II: The spike-Q interval was shortest in the AAI and
      longest in the AAIR+ mode in all patients. Study III: During AAI or AAIR pacing
      the spike-Q interval was longest at night and shortest in the morning. The mean
      spike-Q interval was longer in AAIR than in AAI pacing. No statistical difference
      between the maximal spike-Q intervals observed during the two modes was, however,
      found. Variations in spike-Q interval are generally caused by changes in
      autonomic tone or medication with drugs with antiarrhythmic effect.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7800560
TI  - Invasive and noninvasive methods to predict the long-term efficacy of amiodarone:
      a compilation of clinical observations using meta-analysis.
AB  - BACKGROUND: The method of choice to predict the long-term efficacy of amiodarone
      in the treatment of complex ventricular arrhythmias is unknown. Whether
      electrophysiological testing or Holter monitoring better predicts long-term
      outcome is controversial. METHODS AND RESULTS: We performed a meta-analysis of
      trials using electrophysiological testing or electrocardiographic monitoring to
      predict the efficacy of amiodarone in patients with sustained ventricular
      tachycardia. Arrhythmia recurrence data were combined after homogeneity testing
      across trials. Bayesian estimates and 95% credibility intervals were constructed
      to compare the arrhythmia-free probability among groups. Nine studies using
      electrophysiological testing (351 patients) and three using Holter monitoring
      (167 patients) met criteria for inclusion determined a priori. The combined
      arrhythmia-free probability estimate and credibility intervals were 0.86 (0.78
      0.92) for patients rendered noninducible and 0.81 (0.73-0.87) for patients with
      abolition of ventricular tachycardia during Holter monitoring on amiodarone. With
      this primary analysis, there was no significant difference between the predictive
      value of noninducibility during electrophysiological testing and abolition of
      ventricular tachycardia with Holter. However, if only those electrophysiological
      studies using at least triple extrastimuli were included, arrhythmia-free
      probability for patients rendered noninducible increased to 0.96 (0.88-0.99),
      significantly better than noninvasive testing. CONCLUSIONS: Noninducible
      ventricular tachycardia during electrophysiological testing and abolition of
      ventricular tachycardia during electrocardiographic monitoring on amiodarone
      appear equally predictive of long-term amiodarone success, but this conclusion
      seems dependent on the stimulation protocol used. Although the yield is lower
      (compared to Holter monitoring), ventricular tachycardia rendered noninducible
      with a stimulation protocol using triple extrastimuli is the most highly
      predictive test of long-term amiodarone efficacy.

PMID- 7800561
TI  - A closed-chest pig model of sustained ventricular tachycardia.
AB  - The goal of this study was to develop and explore a closed-chest animal model of
      sustained VT. Seven of 11 domestic pigs had successful induction of myocardial
      infarction by injection of agarose gel microbeads into the left anterior
      descending coronary artery through an inflated balloon angioplasty catheter. Four
      of the first five pigs died and seem to represent a "learning experience." During
      a 3- to 50-day follow-up period, each pig underwent 1-3 electrophysiological
      studies. Sustained, monomorphic VT was induced 1-4 times in 5 of the 7 pigs (a
      total of 19 episodes), was reproducible during the same study in all pigs, and
      could be repetitively induced during successive studies in some. Ventricular
      fibrillation was induced less frequently (nine episodes) and was successfully
      terminated by DC shock in eight episodes. We conclude that a closed-chest pig
      model of VT is feasible and is associated with a relatively high induction rate
      of sustained, monomorphic, and reproducible VT and a relatively low mortality
      rate.

PMID- 7800562
TI  - Power and temperature guided radiofrequency catheter ablation of the right atrium
      in pigs.
AB  - The aim of the present study was twofold: to assess the safety of ablating the
      atrial free wall using RF current; and to assess the effect of a single dose of
      intravenous heparin followed by aspirin once daily to prevent thrombus formation
      after RF ablation. Temperature and power guided catheter ablation were evaluated.
      Twenty pigs were randomized to power or temperature guided unipolar RF catheter
      ablation. Ten animals received a bolus of heparin (150 U/kg) followed by 150-mg
      aspirin daily, and ten served as controls. A mid-sternal thoracotomy was
      performed 5-7 days later. The ability of a lesion to resist an increased
      transmural atrial pressure was examined by inflating a cuff around the pulmonal
      artery. Transmural lesions were found in all animals. Right atrial pressure was
      increased from 5 to 30 mmHg with no sign of perforation. In 11 of 20 (55%)
      animals, 1-3 lesions were found in the lungs (diameter 4-18 mm). The localization
      of these lesions corresponded to the lesions in the atria. There were no
      differences in the energy delivery modes with regard to the number of animals
      with lung lesions. Lesions with thrombus formation were found in four animals in
      the heparin/aspirin group and in nine animals in the control group. The incidence
      of thrombi was significantly smaller in the treatment group. There were no
      differences between temperature and power guided catheter ablation with regard to
      the size of the atrial lesions or to the incidence of thrombus formation.
      Transmural lesions induced in the right atrium by RF energy are resistant to
      increases in transmural pressure. However, lung tissue overlying the ablated
      target may be injured by the RF energy delivered. The combination of a single
      dose intravenous heparin followed by aspirin daily may reduce the incidence of
      thrombus formation.

PMID- 7800563
TI  - Radiofrequency catheter ablation of atrioventricular nodal reentrant tachycardia
      in children.
AB  - Radiofrequency (RF) catheter ablation has been widely used in the treatment of
      cardiac arrhythmias. In atrioventricular nodal reentrant tachycardia (AVNRT), the
      experience has been predominantly in adults. The cardiac electrophysiological
      records of 18 consecutive children undergoing RF catheter AV node modification
      for AVNRT were reviewed. The patients (10 females, 8 males) were 8.2-17.9 years
      of age (mean 13.6 +/- 3.0), weight 15.2-88.1 kg (mean 52.2 +/- 20.8), and height
      103-190 cm (mean 157.1 +/- 21.7). Thirteen were on antiarrhythmic medications (1
      3, average 1.5 drugs/day). All drugs were discontinued 48 hours prior to the
      ablations. The procedures were performed under sedation and local anesthesia. Pre
      and post-AV node modification electrophysiological studies were performed in all
      procedures. The 18 patients underwent a total of 25 procedures (1.39 +/- 0.61 per
      patient): the anterior approach aimed at the antegrade fast pathway in the first
      four patients and the posterior approach aimed at the slow pathway in the
      remainder. The number of energy applications was 8-54 (19.8 +/- 10.7) per
      procedure. The maximum energy used in each procedure was 30-50 watts (33.8 +/-
      8.4). The average energy was 24-50 watts (33.0 +/- 6.8). The fluoroscopy time was
      7.1-73.4 minutes (29.9 +/- 20.0) per procedure, for a total catheterization time
      of 228-480 minutes (300.3 +/- 59.1). Preablation spontaneous or induced AVNRT
      (cycle length 310.4 +/- 55.0 msec) was seen in all except one who had the
      arrhythmia (cycle length 270 msec) on surface ECG.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7800564
TI  - Myocardial coagulation by intraoperative Nd:YAG laser ablation and its dependence
      on blood perfusion.
AB  - To investigate whether the efficacy of intraoperative laser ablation therapy is
      affected by myocardial blood perfusion, we irradiated 11 canine hearts through
      the epicardium with a Nd:YAG laser (10, 20, and 30 J/mm2) using air as the
      medium. Compared coagulated myocardial depth, width, and volume obtained in the
      red beating heart was compared with those in the white nonbeating heart infused
      with 0 degrees C saline (cardioplegic model) via the coronary artery.
      Histologically, the macro- and microscopical findings were very similar. At each
      level of energy, the width and volume of red myocardium coagulated were
      significantly larger than those of white myocardium (P < 0.01). At 30 J/mm2, the
      depth of coagulation of red myocardium was significantly larger than that of
      white myocardium (P < 0.01). The coagulated volume of the white myocardium was
      about 60% of that of the red myocardium. Nd:YAG laser energy was absorbed by
      blood (red color = hemoglobin), and more energy was transferred in the higher
      temperature myocardium. During intraoperative Nd:YAG laser ablation, the presence
      of blood perfusion in cardiac tissue is thought to be an important factor
      affecting safe irradiation.

PMID- 7800565
TI  - Regeneration of pacemaker battery after explantation.
AB  - In an effort to evaluate changes in voltage output of a pulse generator after
      explantation, the output of 33 pulse generators was measured at the time of
      explant and following 3 days of rest (not pacing). Twenty generators were removed
      secondary to elective replacement indicators (ERI) and 13 for other causes. The
      output of ERI generators significantly increased, from 2.62 volts at explant, to
      3.17 volts, 3 days later. The non-ERI generators on the other hand, showed no
      significant change in their output. These observations are important when dealing
      with battery depletion.

PMID- 7800566
TI  - Carotid sinus hypersensitivity and syndrome in patients with chronic atrial
      fibrillation.
AB  - Carotid sinus hypersensitivity (CSH) has been studied in subjects in sinus
      rhythm, but it has never been studied in patients with chronic atrial
      fibrillation (AF). After a finding of CSH in a patient with chronic AF and
      syncope, we studied the effects of carotid sinus stimulation in a group of
      patients with AF. Ten patients with chronic AF and normal ventricular rates who
      complained of dizziness or loss of consciousness underwent right and left carotid
      sinus massage (CSM) during ECG monitoring. A control group of ten patients with
      AF but without neurological symptoms was likewise investigated. CSH was present
      in eight symptomatic patients (5 patients presented right CSH, 1 left and 2
      bilateral CSH), but only in three of the control patients. The mean duration of
      asystole induced by right CSM was 5.94 +/- 2.10 seconds; the mean asystolic
      interval induced by left CSM lasted 8.58 +/- 1.42 seconds. Six patients in the
      symptomatic group had a recurrence of spontaneous symptomatology during CSM, so
      that a diagnosis of carotid sinus syndrome was established. All symptomatic
      patients (8 patients with CSH, 2 patients with ventricular standstills but
      without CSH) received a permanent ventricular pacemaker. Following pacing, all
      patients, except for one with a significant drop of systolic blood pressure
      during CSM, became completely asymptomatic. In elder patients with chronic AF,
      CSH can induce prolonged ventricular asystole, which may be responsible for
      neurological symptoms such as dizziness, presyncope, or syncope, as observed in
      patients in sinus rhythm with carotid sinus syndrome.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7800567
TI  - Optical recordings of ventricular excitability of frog heart by an extracellular
      stimulating point electrode.
AB  - To enhance understanding of the excitability of cardiac muscle during rest, an
      optical technique using the fluorescent voltage sensitive dye di-4-ANEPPS was
      used. Unlike conventional electrical recordings, optical recordings are free from
      electrical artifacts and, therefore, allow the observation of the transmembrane
      potential not only following the stimulation pulse, but also during the pulse
      itself. Transmembrane potentials (Vm) were recorded optically from frog
      ventricular epicardium in calcium containing Ringer's solution directly under an
      extracellular stimulating point electrode. Anodal and cathodal S1 stimuli were
      applied at rest. As observed by previous investigators, the post-pulse excitatory
      responses for cathodal pulses, compared with anodal pulses were greater. Changes
      in transmembrane potential (delta Vm) during the pulse were as expected for a
      passive cable only for low intensity pulses (< 4 x the cathodal threshold of
      excitation in diastole, CTE). However, at the higher intensities necessary to
      produce an excitatory response (> 6-8 x CTE), an "irregular" response in Vm was
      observed--a reversal of the hyperpolarization during an anodal stimulus pulse and
      a reversal of the depolarization during a cathodal stimulus pulse. To elucidate
      further the biophysical basis for this behavior, delta Vm was mapped around the
      stimulating electrode. During stimulation, regions could be observed having a
      response with opposite polarity to that under the electrode (i.e., depolarization
      for an anodal pulse and hyperpolarization for a cathodal pulse). Removal of the
      bath solution or the addition of channel blockers did not eliminate the
      occurrence of these regions. These regions appear to be the basis for the
      irregular behavior of delta Vm directly under the electrode as well as for anodal
      excitation.

PMID- 7800568
TI  - Temperature may be an appropriate sensor for chronotropically incompetent
      patients with postural syncope.
AB  - Chronotropically incompetent patients benefit most from sensor driven rate
      response during exercise. Postural syncope may occur despite the chronotropic
      response because of the failure of currently available sensors to respond
      physiologically to postural changes. Seven chronotropically incompetent patients
      with postural syncope who had a dual chamber rate adaptive pacemaker (Circadia)
      that modulates heart rate in response to temperature change were studied with
      respect to: (1) response to exercise; and (2) head-up tilt (HUT). During
      exercise, continuous-wave Doppler of aortic velocities and two-dimensional
      echocardiographic derived measurements of left ventricular systolic function were
      used to assess cardiac function. Patients exercised longer (by an average of 168
      sec) in the DDDR compared to the DDI mode (P = 0.013). Increase in exercise
      duration was due mostly to the sensor driven increase during DDDR pacing. During
      DDDR pacing, heart rate increased from 71 +/- 6 to 121 +/- 17 ppm compared to 70
      +/- 1 to 103 +/- 21 ppm for the DDI pacing (P = 0.038). Stroke volume as assessed
      by Doppler derived stroke distance (SD) contributed more significantly to the
      cardiac output increase during exercise in the DDI mode (SD increased from 13.4
      +/- 4 to 18 +/- 7 cm in DDI compared to 13 +/- 4 to 14 +/- 2 cm in DDDR mode),
      although these mechanisms were insufficient to fully compensate for failure of
      appropriate chronotropic response. In response to the HUT, right ventricular
      temperature increased from 36.78 degrees C +/- 0.29 degrees C to 36.89 degrees +/
      0.28 degrees C (P = 0.0002), and heart rate increased from 54 +/- 3 to 71 +/- 8
      ppm (P = 0.0003) in the DDDR mode. No significant change in heart rate occurred
      in the DDI mode in response to the HUT. Strong positive correlation of
      temperature and heart rate was noted in all patients in response to HUT (P =
      0.001, R2 = 0.755-0.976). We conclude that temperature sensor responds
      physiologically to exercise and HUT. Therefore, temperature sensing rate adaptive
      dual chamber pacing may be appropriate for chronotropically incompetent patients
      with posture related syncope.

PMID- 7800569
TI  - Clinical experience with a new lead combining active fixation with steroid
      elution.
AB  - The Medtronic lead engineering model number 10335A represents a new concept in
      lead design combining active fixation with steroid elution. It aims for immediate
      stability and low chronic thresholds. Twenty-one leads, 9 atrial and 12
      ventricular, were implanted in 13 patients (10 males, mean age 68; range 22-91
      years). The atrial leads showed no rise in pulse width threshold at a voltage of
      1.6 volts (mean thresholds at implant, 1, and 26 weeks; 0.1 +/- 0.09 msec, 0.15
      +/- 0.04 msec, and 0.1 +/- 0.03 msec, respectively). The ventricular leads had a
      small but significant rise between implant and 1 week at an output of 1.6 volts
      (0.07 +/- 0.03 msec increasing to 0.11 +/- 0.04 msec; P < 0.02) but no
      significant later rise (0.1 +/- 0.04 msec at 2 weeks and 0.1 +/- 0.05 msec at 6
      months). These low chronic thresholds would allow early reprogramming of the unit
      to low voltages resulting in a battery saving with prolongation of the unit's
      life. There were no significant changes in the P and R wave amplitudes, but there
      was a fall in lead impedance in the ventricular leads between implantation and 1
      week (P < 0.02) but none subsequently, and there was no significant change in
      atrial impedance. There were no sensing failures and no lead displacements.
      Despite impressive pacing characteristics, the study was suspended because of a
      high level of mechanical complications. Of the 96 patients implanted worldwide
      with 136 leads there were eight helix deformations, which will require
      redesign.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7800570
TI  - The value of artificial neural network techniques to develop diagnostic systems
      in cardiology.

PMID- 7800571
TI  - The pendulum swings: reappraising prepaid health care systems.

PMID- 7800572
TI  - Syncope and sinus arrest associated with the upper limb-cardiovascular (Holt
      Oram) syndrome.

PMID- 7800573
TI  - Catheter entrapment in the mitral valve apparatus during radiofrequency ablation.
AB  - Catheter ablation of accessory atrioventricular pathways in patients with Wolff
      Parkinson-White syndrome has become an increasingly popular therapeutic option.
      Catheter technology is rapidly evolving, allowing physicians to tailor the choice
      of catheter to the location of the pathway. We describe catheter entrapment in
      the mitral valve apparatus while using a valve mapping catheter with a peanut
      shaped tip to approach a left free-wall pathway retrogradely across the aortic
      valve.

PMID- 7800574
TI  - Radiofrequency catheter ablation of concealed atrio-His bypass tract involved in
      paroxysmal supraventricular tachycardia.
AB  - In a patient with paroxysmal supraventricular tachycardia and without any
      evidence for preexcitation syndrome or dual atrioventricular (AV) nodal pathways,
      the tachycardia reentry circuit consisted of the AV node as an antegrade limb of
      the circuit and a concealed atrio-His bypass tract located in the posterior
      septum as a retrograde limb. During the tachycardia, the atrial potentials in the
      septal region and coronary sinus were inscribed in the QRS complex, and the
      earliest atrial activation site was located in the posterior septum. Ventricular
      extrastimulation at critically short intervals reproducibly demonstrated a
      ventriculo-His-atrial activation sequence with the same earliest retrograde
      atrial activation site as that during the tachycardia. Radiofrequency energy (20
      W) was applied to this earliest activation site during ventricular pacing, which
      resulted in complete ventriculoatrial block within 2 seconds after energy
      application. The antegrade AV conduction property was not affected and the
      tachycardia was no longer induced. The patient has been free from tachycardia
      attack for a follow-up period of 8 months. Therefore, radiofrequency catheter
      ablation for an atrio-His bypass tract is feasible without inducing any AV
      conduction disturbance.

PMID- 7800575
TI  - Left heart pacing and cardioembolic stroke.
AB  - Three patients with inadvertently positioned left heart pacemaker leads were
      admitted for neurological symptoms consistent with embolic stroke. In one of
      them, the pacemaker lead crossed the interatrial septum, the mitral valve, and
      entered the left ventricle. In another it was erroneously placed through the
      subclavian artery, across the aortic valve, and into the left ventricular
      chamber. In the third patient, the right ventricular lead of a DDD pacemaker was
      placed in the coronary sinus and the right atrial lead crossed the interatrial
      septum, and intermittently entered the left ventricular cavity. Once
      anticoagulation was initiated, symptoms resolved; they recurred when the level of
      anticoagulation dropped leading to a major stroke in one of the patients. Two of
      the patients were on aspirin at the onset of symptoms. We believe that every
      approach must be considered to remove the malpositioned lead. Otherwise, full
      dose anticoagulation must be initiated since antiplatelet therapy alone does not
      confer adequate protection against stroke.

PMID- 7800577
TI  - [Advances in obesity treatment].

PMID- 7800576
TI  - Recollections of the beginning of transvenous cardiac pacing.

PMID- 7800578
TI  - [Concentrations of B2-microglobulin and Tamm-Horsfall protein in cyst fluid and
      urinary excretion of these proteins in patients with simple renal cysts].
AB  - The existing classifications of simple renal cysts are based on cyst fluid sodium
      concentration or cyst fluid/plasma sodium ratio. The present study aimed to
      assess: 1) the usefulness of cyst fluid concentrations of beta-2-microglobulin
      (beta-2-MG) as a marker of proximal tubules function and Tamm-Horsfall protein
      (THP) as a marker of distal tubules function to define the origin of renal cysts
      (proximal or distal); and 2) the function of proximal and distal tubules in
      patients with simple renal cysts. 31 patients with simple renal cysts and 10
      healthy subjects were examined. Basing on the cyst fluid/plasma sodium ratio, 25
      cysts were classified as of proximal origin and 6 as of undetermined origin. In
      all patients cyst fluid and plasma concentrations of beta-2-MG, erythropoietin,
      sodium, potassium and total protein were assessed. Urinary excretion of beta-2-MG
      and THP was also estimated and fractional excretion of beta-2-MG was calculated.
      The concentration of beta-2-MG in fluid obtained from cysts of proximal origin
      were significantly higher than in fluid from cysts of undetermined origin (2.26
      +/- 0.36 vs. 0.65 +/- 0.13 mg/l, p = 0.0004). Concentrations of THP (6.85 +/-
      1.21 vs. 3.14 +/- 1.06 micrograms/ml, p < 0.05), erythropoietin (500.6 +/- 176.8
      vs. 42.0 +/- 17.7 mU/ml, p < 0.05) and potassium (4.39 +/- 0.07 vs. 3.13 +/- 0.44
      mmol/l, p < 0.05) were also higher in fluid from proximal cysts than in fluid
      from cysts of undetermined origin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7800579
TI  - [Levels of endothelin-1 in bronchoalveolar lavage fluid of patients with
      bronchial asthma].
AB  - To evaluate the role of endothelin in the pathogenesis of bronchial asthma
      endothelin-1 levels were studied in the bronchoalveolar lavage fluid of
      symptomatic (n = 7) and asymptomatic (n = 10) asthmatic patients and healthy
      volunteers (n = 6). In all patients BAL fluid levels of endothelin-1 was assessed
      by RIA, total protein concentration by Lowry method. Patients with symptomatic
      asthma had increased amount of ET-1 in BAL fluid than asymptomatic asthmatics and
      control group. CONCLUSIONS: 1. Presence of endothelin in BAL fluid indicate that
      this peptide is involved in the pathogenesis of bronchial asthma. 2. Endothelin-1
      BAL fluid levels may correlate with the severity of bronchial asthma.

PMID- 7800580
TI  - [Lipid peroxides and vitamin E in plasma and plasma lipoproteins in blood of
      patients with chronic hemodialysis].
AB  - To investigate a possible oxidative modifications of plasma lipoproteins in
      chronic hemodialyzed patients, lipid peroxide concentrations in plasma and in
      VLDL, LDL and HDL were investigated in 40 patients receiving regular dialysis
      treatment (RDT). Additionally, vitamin E in this patients was also determined.
      The serum and lipoprotein lipid peroxides concentrations were significantly
      increased in RDT in comparison with 36 healthy subjects. The concentrations of
      the main lipoprotein antioxidant--vitamin E were significantly lower in RDT
      patients. There was an inverse correlation (r = -0,767; p < 0.02) between vitamin
      E and peroxides concentration in LDL. Furthermore, a significant increase of
      lipid peroxides in LDL were observed after hemodialysis. The results indicates
      vitamin E deficits in patients undergoing chronic hemodialysis.

PMID- 7800581
TI  - [Effect of misoprostol, a synthetic prostaglandin E analog, on levels of serum C
      peptide in serum and glucose tolerance].
AB  - The aim of the study was to investigate whether oral application of misoprostol
      (MI), which is an analogue of prostaglandin E1, does change the secretion of
      insulin and the blood glucose level. The investigations were carried out in 15
      subjects, aged 21-40 yrs, with a gastric or duodenal ulcer and without any
      disturbances of the digestive tract motility. In 7 of them (group A), without
      stated diabetes a single oral dose of 400 mg MI versus placebo (PL) and 15 min
      later 75 g glucose p.o., was applied in randomized order, on different days, in
      fasting state. In 8 subjects with mild diabetes type II (gr B) MI versus PL and
      after 15 min. i.v. 1.0 mg glucagon was similarly administered. In both groups the
      concentrations of glucose and C-peptide in blood were determined. In comparison
      to PL, the application of MI did not cause any statistically significant
      differences of C-peptide in serum and blood glucose levels neither before and
      after oral glucose loading nor after i.v. administration of glucagon.
      Statistically not significant were also the differences in AUC (p > 0.05).

PMID- 7800582
TI  - [Lactate metabolism in acute myocardial infarction].
AB  - In 18 patients with acute myocardial infarction admitted to the Cardiological
      Care Department within 6 hours after the onset of chest pain, before
      administration of drugs and then in the 2nd, 3rd, 5th and 7th day, the levels of
      glucose, pyruvate, lactate in venous blood, the lactate/pyruvate ratio (L/P) and
      pH, actual hydrocarbons, PCO2 and PO2 in capillary arterialized were determined.
      Depending on the clinical status at admission the patients were classified into 2
      groups: I--without complications (I class according to Killip-Kimbal; n = 10),
      and II--with complications (II-IV class of cardiac failure according to Killip
      Kimbal and/or complex ventricular arrhythmias e.i. III-V class according to Lown
      and heart block of Mobitz--type II and III degree; n = 8). None of the patients
      had diabetes, chronic respiratory tract diseases, renal failure and liver
      cirrhosis. The control group consisted of 11 healthy persons. On the first day of
      myocardial infarction, the significant increase of blood glucose, lactate,
      pyruvate, as well as significant decrease of blood pH, HCO3- and PO2, and non
      significant increase of L/P ratio were observed in both groups as compared to the
      control group. Also there were non significant difference of the glucose,
      lactate, pyruvate L/P ratio and pH, PCO2 and HCO3- values between the I and II
      group on the first day of the acute myocardial infarction, with exception of the
      PO2, which was significantly lower in the group II. In the following days an
      increase of PO2 was observed. Since this effect coincided with a decrease of
      lactate concentration (significant only in the group II) it could be concluded,
      that the observed decrease of the lactate concentration resulted from the higher
      supply of oxygen. The obtained results have shown, that increase of glycaemia
      values and decrease of PO2 values may be considered as biochemical markers for
      hemodynamic complications of acute myocardial infarction.

PMID- 7800583
TI  - [Selected parameters of blood coagulation and fibrinolysis and their relationship
      to the level of diabetes control in patients with insulin-dependent diabetes
      mellitus].
AB  - The aim of the study was to evaluate plasma concentration of fibrinogen, plasma
      activity of antithrombin III (AT-III) and plasma activity of plasminogen
      activator inhibitor (PAI-I) in insulin-dependent diabetic (IDDM) patients and the
      assessment of correlation between them and the parameters of glyco-metabolic
      control comprising glycemia and concentrations of fructosamine and glycated
      hemoglobin HbA1c. Eighteen IDDM patients (mean age 28.3 +/- 11.3 ys, mean
      duration of disease 12.2 +/- 5.3 ys) without over nephropathy and without
      macroangiopathy were investigated. Control group consisted of 8 healthy subjects.
      Plasma fibrinogen concentrations were similar in IDDM patients and in controls
      (3.54 +/- 0.45 g/l and 3.31 +/- 0.54 g/l respectively). Plasma activity of AT-III
      in diabetic patients (90.6 +/- 22.4%) was similar to that in healthy subjects
      (94.6 +/- 25.0%). Fibrinogen concentrations and AT-III activities showed no
      correlation with glycemia and concentrations of fructosamine and HbA1c. Plasma
      activity of PAI-I was significantly lower in diabetics than in controls
      (respectively 1.56 +/- 0.72 U/ml and 2.75 +/- 1.25 U/ml, p < 0.005). PAI-I
      activity correlated negatively with fasting blood glucose (p < 0.05) but did not
      correlate with concentrations of fructosamine or HbA1c. The results suggest that
      glycemic control in diabetic patients do not influence on concentrations of
      fibrinogen and activity of AT-III but diminished activity of PAI-I is related to
      hyperglycemia.

PMID- 7800584
TI  - [Does long-term human recombinant erythropoietin (rHuEPO) influence secretion of
      hormones regulating volume and pressure of arterial blood?].
AB  - This study aimed to assess the effect of anaemia on volume related hormones in
      dialyzed patients with chronic uraemia. Three groups of subjects were examined.
      The first one comprised 34 hemodialyzed patients with severe anaemia (haematocrit
      value < 28%). 17 patients were treated with EPO for 1 year (EPO group) while the
      other 17 patients did not receive rHuEPO (no-EPO group) but were intensively
      monitored biochemically and clinically as patients of the EPO group. The second
      group (HD) consisted of 12 hemodialyzed uraemic patients with a Hct > 30% without
      rHuEPO treatment, while the third one comprised 15 healthy subjects. In patients
      of the EPO and no-EPO group plasma renin activity (PRA), plasma concentration of
      aldosterone (Ald) atrial natriuretic peptide (ANP and vasopressin (AVP) were
      assessed before (0) and after 3, 6, 9 and 12 months of clinical monitoring, while
      in patients of the HD group and in normals the above mentioned parameters were
      estimated only once. EPO treatment improved significantly the Hct value already
      after three months of therapy. No significant changes in PRA and plasma
      concentrations of Ald, ANP and AVP in the noEPO group were noticed during 12
      months of monitoring. In contrast EPO treatment induced a significant, although
      transitory decrease of PRA, Ald and AVP, but an increase of plasma ANP. No
      influence of rHuEPO therapy on blood pressure was noticed.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7800585
TI  - [Influence of nicotinamide on the course of insulin-dependent diabetes mellitus].

PMID- 7800586
TI  - [Essential thrombocythemia--clinical course from personal material].
AB  - The article presents clinical course analysis of essential thrombocythemia in 17
      patients aged 29-82. The diagnostic criteria were the same as described by
      Polycythemia Vera Study Group. Mean platelet level of diagnosis was 1680 x
      10(9)/l. Haemorrhagic complications were observed in 42% of the patients, while
      thrombotic ones or embolisms in 35%. In two cases both types of complications
      occurred. Asymptomatic course of the disease was observed in 5 patients. The
      statistical analysis proved that the patients with platelet count between 900
      1900 x 10(9)/l are in danger of developing thrombotic episodes and thus
      antiaggregation treatment should be considered. If platelet level exceeds 1900 x
      10(9)/l the risk of haemorrhage increases, so antiaggregation treatment is
      contraindicated and thrombocytapheresis is advised instead. The patients was
      started on treatment when platelet count was above 1000 x 10(9)/l in asymptomatic
      cases or with lower platelet level in symptomatic ones. The treatment consisted
      of busulphan, hydroxyurea or interferon alpha (in one of the patients) until
      lowering platelet level below 600 x 10(9)/l.

PMID- 7800587
TI  - [Influence of fish oil on serum lipoprotein level in endogenous
      hypertriglyceridemia].
AB  - The influence of fish oil on the level and composition of lipoprotein fractions
      in hypertriglyceridemic men was evaluated. The observation was performed in 2
      groups of patients, 10 cases each (a cross-over study). In the group I subjects
      received fish oil first, in the dose of 12 grams daily (3.6 g of EPA and DHA) for
      3 weeks, and then, for the next 3 weeks, olive oil in the same dose. Patients
      from the group II received the same oil but in the inverse order. Results after
      olive oil were a control for fish oil. Marked decreases in the serum and VLDL
      triglycerides and also VLDL-cholesterol level after fish oil was shown. Increases
      in LDL and HDL cholesterol were observed. In 9 patients fish oil was given for 6
      weeks. No differences in the serum lipid levels after this period of time in
      comparison with results after 3 weeks were observed.

PMID- 7800588
TI  - [Comparative study of the influence of fish oil and gemfibrozil on levels of
      serum lipoprotein in endogenous hypertriglyceridemia].
AB  - Hypolipemic action of fish oil and gemfibrozil was compared. The study was
      performed in 12 men with endogenous hypertriglyceridemia. Subjects received fish
      oil 12 grams daily (3.6 g of eicosapentaenoic and docosahexaenoic fatty acids)
      for 3 weeks, and then, after an interval of at least 6 weeks, gemfibrozil in the
      dose of 900 mg daily. Results after gemfibrozil were compared with those after
      fish oil. Fish oil was shown to be less effective than gemfibrozil in decreasing
      concentrations of serum triglycerides and triglycerides and cholesterol in VLDL.
      However, the difference did not reach the level of statistical significance. The
      agents differed significantly in their influence on the LDL fraction. Fish oil
      slightly increased and gemfibrozil significantly decreased LDL-chol level. LDL
      apoB increased after fish oil, but did not change after gemfibrozil. It may be
      concluded that fish oils, although effective in decreasing concentrations of
      serum triglycerides and lipid components of the VLDL fraction, are not
      alternative for gemfibrozil in monotherapy of endogenous hypertriglyceridemia.

PMID- 7800589
TI  - [Bio-therapy in hematology: New treatment of non-hodgkin's lymphomas with
      monoclonal antibodies].

PMID- 7800590
TI  - Current concepts in joint replacement.

PMID- 7800591
TI  - Current Concepts in Joint Replacement. Proceedings of a meeting. Orlando,
      Florida, December 1993.

PMID- 7800592
TI  - The closing circle: limitations of total joint arthroplasty.

PMID- 7800593
TI  - The contribution of metallic debris to osteolysis.

PMID- 7800595
TI  - Porous-coated fixation forever.

PMID- 7800594
TI  - Osteolysis: the mechanisms of response.

PMID- 7800596
TI  - Cement for the femur: why not always?

PMID- 7800597
TI  - Porous coating: do we need it?

PMID- 7800598
TI  - Hydroxyapatite in total hip arthroplasty: five-year clinical experience.
AB  - Excellent clinical and radiographic results are seen with HA-coated femoral
      components at 5-year follow up. These stems are well fixed proximally, and the
      transmission of stress is noted to occur at the transition from the coated to
      uncoated stem. Longer follow up is needed to determine if the currently stable HA
      coated implants will become threatened by wear debris and subsequent osteolysis,
      as has been the case in many long-term studies of other hip implants.

PMID- 7800599
TI  - Cementless components: the good, the bad, and the ugly.

PMID- 7800600
TI  - Cemented all-poly cups.

PMID- 7800601
TI  - An algorithm for the management of femoral neck fractures.
AB  - The choice of total hip arthroplasty should probably be reserved for those rare
      patients with preexisting osteoarthritis of the hip in the setting of a
      subcapital hip fracture. Additionally, relative indications for total hip
      arthroplasty may include the presence of contralateral hip disease; the presence
      of metabolic bone disease, which may controvert internal fixation or reasonable
      results with endoprosthetic replacement; and those patients with high activity
      expectations or life expectancy greater than 5 years. Given the diminished
      performance of hemiarthroplasty with time and activity, it may be argued that the
      most cost effective solution to the subcapital hip fracture in the majority of
      patients may be the reduction and internal fixation pathway, with elective
      conversion, when necessary, of the approximately 25% of patients who suffer
      avascular necrosis to total hip arthroplasty. It appears that hemiarthroplasty is
      best suited for the elderly household ambulator, whereas total hip arthroplasty
      is the better alternative either as the elective solution to failed internal
      fixation of femoral neck fractures or in the occasional community ambulator with
      high activity expectations and irreducible femoral neck fractures. Younger
      patients, and those with minimally displaced fractures, should be treated with
      internal fixation in an attempt to preserve the natural hip joint.

PMID- 7800602
TI  - Assessment of the symptomatic total hip.
AB  - This new information has recently been incorporated into a series of algorithms
      for evaluating painful cemented and cementless total hip replacements. As the
      interpretation of many tests varies significantly between cemented and cementless
      components, the approach to these two situations differs accordingly. Careful
      review of sequential plain radiographs remains a mainstay of initial evaluation.
      The sedimentation rate is also a cost effective method of adding useful
      information. Based on this assessment, cemented and cementless components can be
      classified as loose, well fixed, or having lysis without being loose. Subsequent
      evaluation should incorporate new information regarding the effectiveness,
      limitations, and cost of various diagnostic tests available for the evaluation of
      the painful total hip replacement.

PMID- 7800603
TI  - The prevention of pulmonary embolism.

PMID- 7800604
TI  - Metal modularity: caveat emptor?

PMID- 7800605
TI  - Hip arthroplasty: assessment and choices. Fit and fill: fact or fiction?

PMID- 7800606
TI  - Minimum cement technique in stem design.

PMID- 7800607
TI  - Bone graft options: fact and fancy.

PMID- 7800608
TI  - Diagnosis and management of the infected hip.

PMID- 7800609
TI  - New technologies: what, when, and who?

PMID- 7800610
TI  - Osteolysis: new polymers and new solutions.
AB  - The prevention of osteolysis is a complex problem with multiple variables.
      Polyethylene represents one half of the bearing surface. Femoral head size,
      component congruency, and bearing material play a dominant role in the generation
      of particulate debris. In addition to all of these variables, there is a
      significant individual variation of biological response to a given particulate
      load. The industry-wide effort to improve the overall quality of manufactured
      polyethylene products and the introduction of Hylamer as a polyethylene bearing
      surface represent a significant step forward in reducing the problems of
      osteolysis in the next generation of implant patients.

PMID- 7800611
TI  - Biological resurfacing: an alternative to total joint arthroplasty.
AB  - These preliminary observations suggest that the functional repair of adult
      hyaline cartilage is controlled by the entrance and lineage progression of
      uncommitted MSCs into chondrocytes under the direction of specific biological and
      mechanical cues which represent a recapitulation of embryonic events. This
      concept implies that to some extent the regeneration of destroyed articular
      cartilage is limited by an inadequate supply of MSCs from the host and their
      inefficient interaction with the appropriate factors at the local site. Finally,
      the use of autologous cell tissue engineering could provide the basis of an
      important application for the repair of deficient joint surfaces as a result of
      trauma or osteoarthritis.

PMID- 7800612
TI  - The art and science of total knee arthroplasty.

PMID- 7800613
TI  - Cemented cruciate-sacrificing total knee replacement.

PMID- 7800614
TI  - Cruciate-sparing total knee arthroplasty.

PMID- 7800615
TI  - The cementless metal-backed tibia.

PMID- 7800616
TI  - Cementless meniscal bearing knee arthroplasty: 7- to 12-year outcome analysis.

PMID- 7800617
TI  - Cemented metal-backed tibial components.

PMID- 7800618
TI  - The cemented all-poly tibia.

PMID- 7800619
TI  - The uncemented femur: what problems are we solving?

PMID- 7800620
TI  - Management of extensor mechanism complications in total knee arthroplasty.

PMID- 7800621
TI  - Management of periprosthetic fractures.

PMID- 7800622
TI  - Structural allografting in revision total knee arthroplasty.
AB  - While morsellized cancellous autograft or allograft have been shown to be highly
      successful in the management of smaller cavitary defects in revision TKA,
      structural allografts are often required for large, noncontained osseous defects.
      Early clinical results of revision TKA utilizing structural allografts have been
      encouraging with high allograft-host union rates if adequate allograft fixation
      is obtained. The use of intramedullary stems engaging diaphyseal bone is
      recommended to lessen load transmission to the structural allograft and the risk
      of late allograft collapse. Extensive preoperative planning, meticulous operative
      technique, and an extended period of postoperative rehabilitation are required
      for optimal results.

PMID- 7800623
TI  - The case for osteotomy.

PMID- 7800624
TI  - The case for unicompartmental knee arthroplasty.

PMID- 7800625
TI  - The case for total knee replacement in unicompartmental knee arthritis.
AB  - In summary, unicompartmental replacement has narrow indications, involves more
      difficult surgical technique, and has inferior long-term results and revision
      complexity similar to that of tricompartmental replacement. It should be used by
      surgeons who are experienced with the technique and are performing a significant
      number of unicompartmental arthroplasties to justify its increased difficulty.
      Total knee replacement, on the other hand, is suitable for all gradations of knee
      disease, has a straightforward surgical technique, and has excellent long-term
      results. It is the treatment of choice for unicompartmental arthritis in the
      arthroplasty-indicated patient.

PMID- 7800626
TI  - TKA revision after osteotomy.

PMID- 7800627
TI  - Hip challenges: what would you do?

PMID- 7800628
TI  - Knee challenges: what would you do?

PMID- 7800629
TI  - Cementless revision for femoral failure.

PMID- 7800630
TI  - Impaction grafting plus cement for femoral component fixation in revision hip
      arthroplasty.

PMID- 7800631
TI  - Extensor mechanism management in the stiff knee.

PMID- 7800632
TI  - Ligament releases.

PMID- 7800633
TI  - Total knee arthroplasty after high tibial osteotomy.

PMID- 7800634
TI  - Lack of recombination between the Z-linked silver feather pattern locus and the
      break point of a chromosome translocation: a second occurrence.
AB  - A mating was conducted to test the linkage relationship between the Z-linked
      silver locus (S) and the NM 7659 t(Z;1) chromosome translocation. No recombinants
      between the break point and S were recovered (n = 187). A previous study had
      shown no recombination between the S locus and the MN t(Z;3) chromosome
      translocation. The proximity of these two break points and the endogenous
      retrovirus ev21 may indicate an unstable DNA segment in this region.

PMID- 7800635
TI  - The effects of dietary fat on growth performance, carcass composition, and feed
      efficiency in the broiler chick.
AB  - In two experiments broiler chicks were fed nonisocaloric diets with either 0, 3,
      or 7% added lard. Megacaloric percentages of all major nutrients were the same in
      all diets. In Experiment 1 (broiler chicks 0 to 5 d of age), added dietary lard
      did not affect body, heart, spleen, or pancreas weight. Liver weight was
      suppressed by the inclusion of lard in the diet, yet liver composition changed,
      becoming higher in protein and lower in fat. Yolk sac weight decreased during the
      first 5 d posthatch, with the decrease being most pronounced by 3 d of age. There
      were no differences in feed consumption due to treatment in Experiment 1. In
      Experiment 2 (broiler chicks 6 to 11 d of age), added dietary fat resulted in
      differences in liver, body, and fecal excreta composition. Chicks given 7% added
      lard had lower liver fat throughout the trial than chicks fed no added lard.
      Additionally, these chicks had a higher body protein content at 6 and 7 d of age.
      However, body fat only increased in chicks fed 7% added lard by 11 d of age.
      Furthermore, chicks receiving 7% added lard had elevated fecal fat at Day 6, but
      did not consume more feed than chicks receiving 0 or 3% added lard. Additionally,
      chicks fed lard had lower liver weights than those fed 0% added lard.

PMID- 7800636
TI  - Blood clearance of Escherichia coli and evaluation of mononuclear-phagocytic
      system as influenced by supplemental dietary zinc methionine in young turkeys.
AB  - The influence of diets containing Zn-Met on in vitro and in vivo uptake of
      Escherichia coli by the mononuclear-phagocytic system was evaluated. Female
      Nicholas turkeys reared in battery brooders were supplemented with 40 micrograms
      Zn/g as Zn-Met in a corn soybean meal diet from 1 to 3 wk of age. Chemical
      analysis of the basal diets indicated that the basal diets contained 130
      micrograms Zn/g and the Zn-Met diets contained 165 micrograms Zn/g. Each diet was
      fed to three replicate pens of 8 birds in Experiment 1 and three pens of 16 birds
      in Experiment 2. Body weight gain, feed conversion (FC), and clearance of
      injected E. coli from blood were determined in Experiments 1 and 2. Abdominal
      exudate cells (AEC) were recruited by intra-abdominal Sephadex injection.
      Substrate adherence potential and incidence of macrophages in AEC, phagocytosis
      of E. coli in vitro in terms of percentage phagocytic macrophages, and number of
      internalized E. coli per phagocytic macrophage, were quantified in Experiment 1.
      Plasma Zn concentrations and plasma alkaline phosphatase activity (ALKP) were
      determined in Experiment 2. Supplemental Zn-Met improved 3-wk BW gain (P < or =
      .003) only in Experiment 2. Dietary Zn-Met increased mean adherence of cells by
      69% (P < or = .001). The number of phagocytized E. coli per macrophage did not
      differ significantly between treatments; however, E. coli clearance from blood
      was significantly improved in poults receiving Zn-Met in Experiment 2. Plasma Zn
      was higher in poults supplemented with Zn-Met prior to and after E. coli
      administration (P < or = .02).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7800637
TI  - Individual and combined toxicity of T-2 toxin and cyclopiazonic acid in broiler
      chicks.
AB  - The effects of feeding 6 mg T-2 toxin (T-2) and 34 mg cyclopiazonic acid (CPA)/kg
      of diet singly and in combination were characterized in male broiler chicks from
      1 d to 3 wk of age. Body weights were depressed by T-2, CPA, and the combination
      of T-2 and CPA. There was a significant synergistic interaction between T-2 and
      CPA for relative liver and kidney weights and serum cholesterol and triglyceride
      concentrations and a significant interaction between T-2 and CPA for 3-wk body
      weights and relative bursa of Fabricius weights, which were less than additive.
      Neither the efficiency of feed utilization nor mortality was affected by dietary
      treatments. Oral lesions were present in a majority of the chicks fed diets
      containing T-2 with or without CPA. When compared with controls, other variables
      measured exhibited additive or less than additive toxicity. These data
      demonstrate that T-2 and CPA alone and in combination can cause reduced
      performance and adversely affect broiler health. The effects of these mycotoxins
      may be exacerbated by other factors when under field conditions; hence, the
      potential detrimental effects of these two mycotoxins when present alone or in
      combination cannot be dismissed.

PMID- 7800638
TI  - Effects of light and temperature on anticipatory feeding by broilers.
AB  - The objective of this research was to determine the effects of daily cycles of
      light intensity and temperature on anticipatory feeding by broilers. Broilers
      were maintained on litter in environmental chambers with feed provided for 12
      h/d. Feed consumption was recorded by computer every 30 min and summarized for 2-
      and 24-h periods. In Trial 1, lighting was at 16 lx for 12 h and at 94 lx for 12
      h each day. Feed was provided either during the 16- or 94-lx period. Broilers
      consumed more feed at the onset of feeding and at the end of the feeding period
      than at other times in both treatments. In Trials 2 and 3, the chamber
      temperature was cycled such that a 12-h feeding period was provided at either 32
      or 16 C. Broilers consumed more feed at the onset of feeding than at other times
      but did not increase consumption at the end of the feeding period. The results
      indicate anticipatory feeding is enabled by cyclic lighting intensity but not by
      cyclic temperature. In Trial 4, the light intensity and temperature were cyclic.
      Feed was provided during high light intensity and at maximum temperatures. Feed
      consumption increased when temperature was declining, indicating broilers
      responded to the reduced temperature. The results show that a period of darkness
      is not required for anticipatory feeding and that environmental temperatures and
      lighting typical of curtain-sided broiler houses alter feed consumption patterns.

PMID- 7800639
TI  - Sensitivity of field isolates of Eimeria from two broiler complexes to
      anticoccidial drugs in the chicken.
AB  - The spectrum of resistance to seven currently used anticoccidial drugs in
      isolates of Eimeria obtained from farms two broiler complexes was examined. All
      isolates were resistant to monensin, salinomycin, and narasin. Lasalocid was more
      effective in controlling coccidiosis than the other ionophores, although most
      isolates were classified as resistant to the drug. The majority of isolates were
      sensitive or showed reduced sensitivity to robenidine, clopidol, and decoquinate.
      It was concluded that for drugs that have been used extensively (e.g., monensin
      and salinomycin), examination of isolates from one or two farms may give results
      applicable to the entire complex. For drugs that have been used infrequently,
      however (such as robenidine, clopidol, and decoquinate), examination of isolates
      from at least five farms would be desirable to establish the spectrum of drug
      sensitivity.

PMID- 7800640
TI  - Effect of cecal cultures lyophilized in skim milk or reagent 20 on Salmonella
      colonization in broiler chicks.
AB  - Mixed cultures of cecal bacteria that were grown under continuous flow anaerobic
      conditions were prepared as lyophilized powder in skim milk or Reagent 20 (R-20;
      a mixture containing sucrose and bovine serum albumin fraction V) and compared
      with broth cultures for reduction of Salmonella typhimurium enteric colonization.
      Day old broiler chicks were provided a standard corn-soybean diet with: 1) no
      culture, (control); 2) broth culture administered by crop gavage; 3) broth
      culture added to the drinking water; 4) culture lyophilized in skim milk and
      added to drinking water; 5) culture lyophilized in skim milk in gelatin capsules
      and force-fed; 6) culture lyophilized in R-20 and added to drinking water; and 7)
      culture lyophilized in R-20 in gelatin capsules and force-fed. All groups were
      challenged on Day 3 with 10(4) cfu of S. typhimurium per chick. Culture by crop
      gavage, culture in the drinking water, skim milk powder in capsules, and R-20
      powder in the water and in capsules significantly (P < .05) reduced mean
      Salmonella colony-forming units in cecal contents by 3.21 to 5.26 log10 units at
      10 d of age. Likewise, the number of cecal-culture-positive chicks in the same
      groups was significantly less than controls with reductions of 27 to 67%. The
      numbers of Salmonella per gram of cecal contents and the percentage of cecal
      culture-positive chicks in the skim milk powder in the drinking water group were
      not different from control chicks in one of two experiments.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7800641
TI  - Symposium: regulation of drugs and chemicals used by the poultry industry.
      Introduction.

PMID- 7800642
TI  - Regulation of drugs and chemicals used by the poultry industry. Good
      manufacturing practices.
AB  - Good manufacturing practices (GMP) are required to be followed in the use of
      animal drugs to produce medicated feeds. The authority is found in the federal
      Food, Drug, and Cosmetic Act, which states that medicated feed can be deemed
      adulterated if GMP were not followed in its production. This authority has been
      translated into GMP regulations applicable to all medicated feed production. More
      detailed GMP are imposed on those using high potency sources of drugs that
      require a withdrawal period (Category II). Less detailed GMP are imposed on all
      other drug uses (Category I and lower potency sources of Category II). Facility
      registration, medicated feed applications, and biennial inspections are also
      imposed on those required to follow the more detailed GMP regulations. The basic
      thrust of the regulations is assurance that drug use is correct in all respects
      and that the integrity of all medicated and nonmedicated feeds is maintained. The
      objective is food free of illegal drug residues, i.e., food safety. The GMP
      regulations are based on joint industry-government endeavor and reflect the
      practical realities of feed manufacturing. They are, for all practical purposes,
      good business practices assuring that medicated feeds make a positive
      contribution to food production and consumer confidence.

PMID- 7800643
TI  - Regulatory process for drugs used by the poultry industry.
AB  - The availability of safe and effective drugs to treat and control poultry
      diseases and to enhance the efficiency of poultry production depends on the rate
      at which new drugs are approved by the Food and Drug Administration. This paper
      briefly describes the components of the regulatory approval process for a new
      animal drug for use in food-producing animals, with specific reference to some
      problems encountered in the approval process for poultry drugs.

PMID- 7800644
TI  - Chemicals used by the poultry industry.
AB  - The safe and effective use of chemicals within the live production phases of the
      poultry industry requires the implementation of integrated health programs.
      Chemical programs will vary with regard to phase, intended usage, and method and
      frequency of application. The term "chemicals" herein presented excludes drugs
      and non-nutritive feed additives, with primary emphasis on sanitation products
      (i.e., detergents, disinfectants, sanitizers, deodorizers, descalers, and
      possible combinations), pesticides (i.e., insecticides and rodenticides), and
      brief mention of soil litter treatments for environmental management of air
      quality at the farm level. Chemical usage by phase, location, and frequency of
      application are summarized. Products that are effective, environmentally and user
      friendly, and applied within label specification will provide for safe,
      economical, and long-term success of poultry health programs. Such programs must
      be supported by management and maintained through education and product
      stewardship administered cooperatively with chemical suppliers, technical
      consultants, and end users.

PMID- 7800645
TI  - Rate of passage of barley diets with chromium oxide: influence of age and poultry
      strain and effect of beta-glucanase supplementation.
AB  - Three-week-old broiler chicks and 1-yr-old Leghorn cocks were used to determine
      the effect of beta-glucanase addition (experimental product from Trichoderma
      longibrachiatum) to a 60% barley-based diet on rate of feed passage, transit
      time, and mean retention time. Fecal chromium oxide content was used to calculate
      cumulated and noncumulated excretion data. A Hill equation was chosen to test the
      goodness of fit of cumulative excretion curves. Time of 50% (T50) and 1% (T1)
      chromium excretion, calculated from cumulative excretion curves, were affected by
      beta-glucanase addition, but this effect also was influenced by age or strain. In
      broiler chicks, T50 (P < .02) and T1 (P < .06) decreased with beta-glucanase
      addition. In cocks, T50 (P < .04) and T1 (P < .05) increased with beta-glucanase
      addition. Noncumulative excretion data yielded similar results. In the absence of
      beta-glucanase, peak chromium excretion occurred 1 h later in broiler chicks than
      in cocks. These differences in feed passage rate may explain why intestinal
      viscosity caused by the presence of beta-glucan did not act in the same manner in
      broiler chicks as in cocks. When beta-glucanase was added, the age-related
      difference was removed and rates become similar. In broiler chicks, the rate of
      feed passage is related to feed intake. Thus, this could explain the different
      effects in terms of feed utilization.

PMID- 7800646
TI  - Ideal amino acid profile for chicks during the first three weeks posthatching.
AB  - Two chick bioassays with chemically defined amino acid (AA) diets were conducted
      to compare three different AA profiles: the NRC 1984 and NRC 1994 requirement
      profile and the Illinois Ideal Chick Protein (IICP) AA profile. The two battery
      studies involved chicks during the 2nd and 3rd wk after hatching. In Assay 1,
      indispensable AA (including glycine and proline) were ratioed to lysine according
      to requirement ratios present in NRC 1984 and NRC 1994, with digestible lysine
      set at either deficient (.80% of diet) or superadequate (1.12% of diet) levels
      for the purified diet in question. All diets were kept isonitrogenous (2.83% N)
      by varying the level of L-glutamic acid. At .80% lysine, chicks fed the NRC 1994
      AA profile gained 60% faster (P < .01) than those fed the NRC 1984 AA profile.
      With excess digestible lysine (1.12%) and all other indispensable AA increased
      proportionately, chicks fed NRC 1994 still out-gained those fed NRC 1984 by 13%
      (P < .05). Ratios of AA (with respect to lysine) in NRC 1994 were equal to or
      higher than those in IICP, except for histidine. This was due to a lower
      estimated lysine requirement in NRC 1994 than that used for IICP. When NRC 1994
      was compared with IICP in a chick bioassay involving isonitrogenous diets (2.36%
      N) and digestible lysine set at a deficient level of .90%, weight gain and feed
      efficiency were similar between diets. This result suggested that most of the
      indispensable AA in the NRC 1994 AA profile were too high relative to lysine,
      probably because lysine, the reference AA, was too low relative to the other
      AA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7800647
TI  - Continuous submarginal phosphorus with broilers and the effect of preslaughter
      transportation: carcass defects, further-processing yields, and tibia-femur
      integrity.
AB  - Broiler males were given a series of feeds from 0 to 8 wk having all nutrients
      advocated by the NRC (1984) and were compared with birds offered feeds with
      available P continuously 10% below recommendation. At termination, birds in pens
      were divided for cooping, and coops were either subjected to 6 h of truck
      transportation and 4 h of preslaughter rest or held stationary for 10 h. High
      summer temperatures existed throughout experimentation, and low dietary P reduced
      body weight gain through the first 6 wk, whereas an advantage in feed conversion
      and mortality occurred from 6 to 8 wk. Weight loss increased when birds were
      subjected to transportation, regardless of P nutriture, and a portion of the loss
      was recovered during processing as gain in relative chilled carcass yield.
      Proportions of abdominal fat and skinless boneless meats from chilled carcasses
      were unaltered, regardless of treatment. Increased incidence of deformed
      drumsticks occurred because of low P as did drumstick bruising, which was further
      accentuated when birds had been transported. Back bruising was prominent when P
      was adequate and birds were held stationary, whereas the converse occurred with
      transportation. Tibia length was reduced as a consequence of low P, whereas the
      femur suffered in terms of decreased mineral density at the epiphyses and
      resistance to Instron-applied stress. Although transportation in itself did not
      affect any bone measurement, inadequate P weakened the skeleton to increase
      likelihood of carcass defects during preslaughter stress.

PMID- 7800648
TI  - Changes in functional qualities of turkey eggshells in strains selected for
      increased egg production or growth.
AB  - Much past research has been devoted to physical eggshell qualities, i.e., weight,
      deformation, or egg density, but little research has investigated the functional
      eggshell qualities when expressed in terms of eggshell conductance to gases.
      Conductance is a measure of the ease with which gases diffuse across the pores of
      the shell and is (by Fick's law) determined by the number and geometry of the
      individual pores. The objective of the present study was to determine changes
      that have occurred in functional eggshell characteristics (eggshell conductance)
      following selection for egg production or growth over nearly 30 generations.
      Major changes have occurred in the physical dimensions of eggs from selected
      lines of turkeys compared with their respective randombred controls. Egg weights
      increased 11% due to selection for growth and decreased 14% due to selection for
      egg production. Other measurements such as length and width increased
      allometrically with egg weights. Selection for egg production has decreased the
      physical dimensions (egg weight, volume, or surface area) of eggs, and selection
      for growth has increased the same measurements, but adjustments have not been
      made by selected hens to increase or decrease the functional characteristic
      (conductance) allometrically (conductance constants). An interaction was observed
      in eggshell conductance constants as the hens aged, suggesting that genetic
      selection may affect functional characteristics. This suggests that the
      energetics of embryonic development may be different in eggs from turkey hens of
      various ages. Energetics may result in poor hatchability and poult quality. It
      can be concluded that as the hens aged the conductance and conductance constants
      did not change allometrically with increasing egg weight.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7800649
TI  - Rhodanese (thiosulfate:cyanide sulfurtransferase) distribution in the digestive
      tract of chicken.
AB  - In this study the level of rhodanese (thiosulfate:cyanide sulfurtransferase)
      activity in different regions of the digestive tract of chicken was determined
      and compared with that in the liver, heart, kidney, and lung. All tissues studied
      contained rhodanese. The highest specific activity of rhodanese was in the
      submucosal layer of proventriculus, followed by liver, heart, the mucosal layer
      of cecum, rectum, and kidney. The lowest level was present in lung. These results
      suggest that in the chicken part of the ingested cyanide is detoxified in the
      digestive tract, mainly by the proventriculus, and part of the absorbed cyanide
      is metabolized by hepatic rhodanese.

PMID- 7800650
TI  - Effect of age and presence of perches during rearing on tonic immobility fear
      reactions of broiler breeder pullets.
AB  - Broiler breeders were housed in pens in an all-litter house with an 8-h
      photoperiod from hatching to 20 wk of age. They were reared either in the
      presence or absence of perches (7 cm per bird) and on either a 14% or a 17% CP
      diet. The duration of the tonic immobility (TI) fear response was measured in 15-
      and in 20-wk-old birds; each pullet was tested individually and once only. There
      was an apparent age-related increase in the duration of TI, which was attenuated
      by the provision of perches during rearing. The results are discussed in terms of
      maturational and environmental influences on the development and alleviation of
      fear.

PMID- 7800651
TI  - Local anaesthetic bupivacaine alters function of sarcoplasmic reticulum and
      sarcolemmal vesicles from rabbit masseter muscle.
AB  - The effects of local anaesthetics, bupivacaine and lidocaine, on Ca2+ flux
      behaviour of sarcoplasmic reticulum and on sarcolemmal functions were studied in
      the rabbit masseter muscle. The experiments were performed on sarcoplasmic
      reticulum and sarcolemmal vesicles prepared at 1 to 10 days after injection of
      local anaesthetics or saline into masseter muscle as well as on sarcoplasmic
      reticulum vesicles prepared from non-treated rabbits (for assessment of the
      effect on in vitro incubation with local anaesthetics). Bupivacaine potently
      reduced the efficiency of active sarcoplasmic reticulum Ca2+ transport as
      evaluated by coupling ratio (Ca2+ transported/ATP hydrolyzed, in the presence of
      oxalate) at 3 days after the injection; there was only a slight degree of
      uncoupling of Ca2+ transport from ATP hydrolysis with lidocaine injection.
      Bupivacaine but not lidocaine, at 3 days after injection, decreased both the
      apparent permeability of sarcoplasmic reticulum vesicles to Ca2+, determined by
      measuring net efflux of Ca2+ after stopping pump-mediated fluxes, and the steady
      state Ca2+ load in sarcoplasmic reticulum, but had no effect on overall turnover
      of the Ca2+ATPase. The effects of bupivacaine on apparent sarcoplasmic reticulum
      Ca2+ permeability and steady-state Ca2+ load were inhibited by a Ca2+ antagonist
      verapamil. The reduction of Ca2+ uptake of sarcoplasmic reticulum and the
      protective effect of verapamil were reproduced in unfractionated homogenates
      prepared at 3 days after bupivacaine injection. In vitro exposure of sarcoplasmic
      reticulum vesicles to bupivacaine (0.5 to 50 mM) reduced steady-state Ca2+ load
      in a dose-dependent manner. The observed effect elicited by bupivacaine (25 mM)
      was partially protected by procaine, an inhibitor of Ca2(+)-induced Ca2+ release
      from sarcoplasmic reticulum, or by specific closure of the sarcoplasmic reticulum
      Ca2+ release channel by ryanodine, suggesting the possibility that in vitro
      exposure of sarcoplasmic reticulum vesicles to bupivacaine may produce an
      increase in apparent permeability of sarcoplasmic reticulum to Ca2+. In
      sarcolemma, bupivacaine reduced Na+,K(+)-ATPase and Na(+)-Ca2+ exchange
      activities at 3 days after injection; the effects on sarcolemmal vesicles were
      prevented by verapamil. These results suggest that although the effects elicited
      by bupivacaine injection and the in vitro exposure to bupivacaine on steady-state
      Ca2+ load of sarcoplasmic reticulum vesicles were similar, the membrane
      properties of the vesicles from bupivacaine-treated masseter muscles and those
      from normal untreated muscles may not be the same, which indicates that pure
      bupivacaine effect is due partly by an effect on ryanodine- and procaine
      sensitive Ca2+ channels.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7800652
TI  - Changes in the contractile responses to carbachol and in the inhibitory effects
      of verapamil and nitrendipine on isolated smooth muscle preparations from rats
      subchronically exposed to Pb2+ and Zn2+.
AB  - Male Wistar rats were exposed to Pb2+ or Zn2+ and to Pb2+ + Zn2+, receiving
      Pb(CH3COO)2 or/and ZnSO4 with drinking water for 30 days. Cumulative
      concentration-effect curves for carbachol were obtained in ileum and trachea
      isolated from control and heavy metal-treated rats. The effect of the Ca2+
      channel blockers on the carbachol-induced contractions was studied by addition of
      increasing concentrations of verapamil or nitrendipine to the bath solution 20
      min. prior to carbachol. The results showed that exposure of rats to heavy metals
      in doses which did not change the body weight and behaviour, altered the
      contractile responses to carbachol. The sensitivity to carbachol was higher in
      preparations from the ileum of Zn(2+)-exposed rats as compared to controls, while
      a tendency towards decreasing this sensitivity was observed in ileal preparations
      from Pb(2+)-treated animals. The concentration-effect curves for carbachol in
      ileal preparations from Pb2+ + Zn(2+)-treated rats did not differ from those in
      the preparations from untreated rats. The inhibitory effect of the Ca2+ channel
      blockers on the contractility of ileal and tracheal preparations from treated
      rats was weaker as compared to that in controls.

PMID- 7800653
TI  - Uptake of nicotine in hair during controlled environmental air exposure to
      nicotine vapour: evidence for a major contribution of environmental nicotine to
      the overall nicotine found in hair from smokers and non-smokers.
AB  - Hair from smokers and non-smokers has been exposed in a dynamic exposure chamber
      to air nicotine concentrations ranging from 1.5 to 45 and from 20 to 2000
      micrograms/m3 for 8 weeks and 72 hr, respectively. Accumulated hair nicotine was
      quantified by GC/MS. Hair was also collected for direct measurements of nicotine
      in 0-2, 2-4 and 4-6 cm segments from the scalp. Human hair showed a high affinity
      for air nicotine and the chamber experiments revealed a linear relationship
      between the initial hair uptake rates of nicotine and the duration of exposure at
      all air nicotine concentrations applied. Hair nicotine uptake rate decreased with
      time after 4 to 6 weeks exposure to 15 and 45 micrograms/m3 air concentrations of
      nicotine, but not to the 1.5 micrograms/m2 nicotine concentration. Ratio between
      the hair uptake rate of nicotine and the applied air concentration of nicotine
      decreased with increasing air concentrations of nicotine. Segment analysis of
      hair revealed an outward increasing gradient of nicotine in hair. Hair uptake
      pattern of air nicotine suggests the uptake to be governed by an equilibrium
      between nicotine in air and nicotine on the hair surface, possibly combined with
      a slower diffusion process of nicotine from the hair surface into the hair core.
      The hair segment analysis of nicotine indicates that environmental nicotine is
      the dominating contributor to the overall nicotine found in hair both from
      smokers and non-smokers.

PMID- 7800654
TI  - Nicotine in hair of smokers and non-smokers: sampling procedure and gas
      chromatographic/mass spectrometric analysis.
AB  - A gas chromatographic/mass spectrometric method for analysis of nicotine in scalp
      hair and measurements of nicotine in hair from 20 smokers and non-smokers with a
      one year interval are presented. The gas chromatographic/mass spectrometric
      method, based on selected ion monitoring of the ion m/z 162, with ions m/z 133
      and 84 as qualifier ions, allows a highly selective and sensitive detection of
      nicotine in hair samples avoiding interference from other chemicals present in
      hair. Nicotine is extracted after alkaline dissolution i 5M NaOH. The sampling
      procedure takes into account that significant amounts of nicotine in hair is
      probably adsorbed and deposited from atmospheric air. In consequence, the hair
      samples must be taken from a site with sufficient contact with surrounding air
      and the measured concentration of nicotine must be related to the length of the
      hair segment and its distance from the scalp. Our study demonstrated very clear
      and statistically significant differences in the concentrations of nicotine in
      hair from smokers and non-smokers, a high reproducibility of hair nicotine
      measurements over time, and that the presented method is sensitive enough to
      detect individual changes not only in smoking habits, but also in environmental
      nicotine exposure.

PMID- 7800655
TI  - Changes in caffeine, lidocaine and trimethadione metabolism in carbon
      tetrachloride-intoxicated rats as assessed by a "cocktail" study.
AB  - We investigated the possibility of predicting liver damage from changes in the
      serum concentrations of caffeine (10 mg/kg), lidocaine (4 mg/kg) and
      trimethadione (4 mg/kg), which are metabolized catalysed by different cytochrome
      P450 (P450) and/or are dependent on blood flow, in rats with carbon tetrachloride
      (CCl4: 0.25 ml/kg)-induced liver injury using a strategy referred to as a
      "cocktail" study. These 3 probe drugs were simultaneously administered
      intravenously. The half-lives (t1/2) of caffeine, lidocaine and trimethadione
      were significantly longer in the CCl4-treated group than in oil-treated controls,
      but no significant differences were observed in mean apparent volumes of
      distribution (Vd). Serum total body clearance (CL) values of all three drugs were
      markedly reduced in CCl4-treated animals. In rats with liver damage, the
      production of 3 metabolites (theobromine, paraxanthine and theophylline) of
      caffeine in addition to the only metabolite (dimethadione) of trimethadione after
      intravenous administration of probe drugs were significantly reduced compared to
      those of controls. These findings suggest that each probe drug, metabolized by
      different or partially overlapping P450, is useful in evaluating drug-oxidizing
      capacity in liver disease.

PMID- 7800656
TI  - Sensory irritation effects of n-propanol and ethylbenzene after pretreatment with
      capsaicin or indomethacin.
AB  - Irritation of upper respiratory tract (sensory irritation) due to two model
      solvents, ethylbenzene and propanol, were investigated from their reflex-induced
      decrease in respiratory rate in mice. Intranasal application of capsaicin
      decreased the sensory irritation response of both solvents, indicating that at
      least part of the sensory irritation effect must occur as a result of activation
      of capsaicin sensitive afferent nerves. The vehicle used for the application of
      capsaicin in itself decreased the respiratory rate strongly, either caused by
      effects on the upper respiratory tract or on the lungs. This demonstrates the
      need for a formulation of a pharmacologically inactive vehicle for nasal
      application of lipophilic substances. Pretreatment with indomethacin had no
      influence on sensory irritation of any of the solvents. This suggests that
      sensory irritation is caused by a direct interaction between receptors on the
      trigeminal nerves and the vapours rather than being an indirect effect of tissue
      damage giving rise to metabolites from the cyclooxygenase pathway.

PMID- 7800657
TI  - Alterations of lidocaine and pentylenetetrazol-induced convulsions by
      manipulation of brain monoamines.
AB  - The thresholds for pentylenetetrazol and lidocaine-induced clonic convulsions
      were significantly influenced by manipulation of brain biogenic amines.
      Pretreatment with inhibitors of monoamine synthesis, alpha-methyl-p-tyrosine and
      p-chlorophenylalanine, caused significant decreases in brain monoamine contents
      and pentylenetetrazol seizure threshold, while the threshold for lidocaine
      induced convulsions was significantly increased by either treatment. Moreover,
      the inhibitor of dopamine-beta-hydroxylase, disulfiram, caused significant
      decrease in brain noradrenaline (NA) and significant increase in brain dopamine
      (DA) contents. The threshold for pentylenetetrazol-induced convulsions was
      decreased by treatment with disulfiram, while that of lidocaine was increased by
      the same treatment. Furthermore, treatment with L-dihydroxyphenylalanine (L-DOPA)
      caused significant increase in brain DA contents, while 5-hydroxytryptophan (5
      HTP) treatment caused significant increase in brain 5-hydroxytryptamine (5-HT)
      contents, but the thresholds for lidocaine and pentylenetetrazol-induced
      convulsions were not influenced by either treatment. These results may suggest
      that the brain monoaminergic systems, different from their ability to inhibit
      control of pentylenetetrazol seizures, act to potentiate lidocaine-induced
      convulsions.

PMID- 7800658
TI  - Effect of chronic treatment with ICI D7114, a selective beta 3-adrenoceptor
      agonist, on macronutrient selection and brown adipose tissue thermogenesis in
      Sprague-Dawley rats.
AB  - ICI D7114 is a selective beta 3-agonist which stimulates brown adipose tissue
      thermogenesis. In the present study the effects of 18 days treatment with ICI
      D7114 (2 mg/kg/day orally) on macronutrient selection and brown adipose tissue
      thermogenesis were investigated in Sprague-Dawley rats. The rats were maintained
      on a free-feeding self-selection paradigm with three pure macronutrient diets of
      carbohydrate, fat and protein. Treatment with ICI D7114 did not change the
      macronutrient selection or total calories consumed by the rats. To monitor the
      thermogenic activation of brown adipose tissue the binding of [3H]GDP to brown
      adipose tissue mitochondria was measured. The treatment with ICI D7114 increased
      the binding of GDP both when expressed as total binding per lobe (P < 0.001) and
      per mg of protein (P < 0.01). It is concluded that ICI D7114, used in doses
      affecting brown adipose tissue thermogenesis, does not change the macronutrient
      selection or total energy intake in Sprague-Dawley rats.

PMID- 7800659
TI  - Assay of linuron and a pesticide mixture commonly found in the Italian diet, for
      promoting activity in rat liver carcinogenesis.
AB  - The herbicide linuron and a mixture of 15 pesticides commonly found in the
      Italian diet have been assayed for promoting activity in rat liver
      carcinogenesis. Composition of the pesticide mixture was: benomyl (19.55%);
      dithiocarbamates (20.67%); thiabendazole (14.94%); diphenylamine (14.25%);
      chlorthalonil (13.13%); procymidone (7.96%); fenarimol (1.95%); chlorpropham
      (0.70%); vinchlozolin (0.28%); methidathion (2.37%); chlorpyriphos-ethyl (2.09%);
      parathionmethyl (1.00%); chlorfenvinphos (0.27%); parathion (0.70%); pyrimiphos
      ethyl (0.14%). To determine promoting activity we evaluated induction of
      preneoplastic foci in diethylnitrosamine-initiated hepatocytes, by positive
      gammaglutamyl-transpeptidase (GGTase) staining in liver slides, and peroxisome
      proliferation by peroxisomal-dependent catalase and palmitoyl-CoA-oxidase dosage.
      For the assay, groups of male Sprague-Dawley rats were initiated with 100 mg/kg
      diethylnitrosamine intraperitoneally and, one week later, given 150 mg/kg/day
      linuron or 10 mg/kg/day pesticide mixture, administered by gavage three days a
      week. All rats were 2/3 hepatectomized at the beginning of the 3rd week. All
      treatments were terminated at the end of the 8th week, and the rats were
      sacrificed one week later. No significant increases in number and area (mm2) per
      slide unit area (cm2) of GGTase-positive foci could be observed in linuron
      treated rats (5.84 +/- 1.62/cm2; 0.139 +/- 0.041 mm2/cm2) with respect to
      controls only initiated with diethylnitrosamine (4.47 +/- 1.30/cm2; 0.182 +/-
      0.078 mm2/cm2). After treatment with the pesticide mixture, the number of
      preneoplastic foci was instead significantly increased (6.91 +/- 2.05/cm2)
      although the area was not (0.188 +/- 0.128 mm2/cm2). Moreover, no increases in
      the peroxisome proliferation enzymatic markers were observed in either treated
      groups. The results imply a possible carcinogenic risk for the population
      stemming from promoting activities of pesticide mixtures.

PMID- 7800660
TI  - Age related effects of di(2-ethylhexyl)phthalate on hepatic cytochrome P450
      monooxygenases in Wistar rats.
AB  - Age related response of di(2-ethylhexyl)phthalate (DEHP) was studied by
      administering the plasticizer (2000 mg/kg, orally) to 3, 6 and 10 week old wistar
      rats for 1, 7 or 15 days and determining the activity of hepatic P450
      monooxygenases. Single administration of DEHP decreased the cytochrome P450
      contents and activity of arylhydrocarbon hydroxylase, aniline hydroxylase and
      ethylmorphine N-demethylase at all the age groups while repeated exposure induced
      them with maximum alterations occurring in 3 week old rats. Repeated
      administration for 15 days, on the other hand, caused a decrease in the
      cytochrome P450 content and the activity of arylhydrocarbon hydroxylase, aniline
      hydroxylase and ethylmorphine N-demethylase only in the 3 week old rats. The 6
      and 10 week old rats exposed to the same schedule of DEHP showed an inhibition in
      the activity of arylhydrocarbon hydroxylase and an increase in the activity of
      aniline hydroxylase and ethylmorphine N-demethylase, which was however lower than
      that seen after 7 days of exposure to DEHP in the respective age group of
      animals. Our data have indicated the differences in the sensitivity of the P450
      monooxygenases towards DEHP and its metabolites amongst 3, 6 and 10 week old
      animals.

PMID- 7800661
TI  - Short chain fatty acids relax isolated resistance arteries from the human ileum
      by a mechanism dependent on anion-exchange.
AB  - Ileal resistance arteries (internal diameter 184-337 microns) were discussed out
      under microscope and mounted in a microvascular myograph for isometric tension
      recording. Experiments were designed to test compounds trophic to the small
      intestine, namely, epidermal growth factor, glutamine and the three short chain
      fatty acids, acetic, propionic and butyric acid, for effects on vascular tone.
      Glutamine in concentrations up to 30 mM and epidermal growth factor in
      concentrations up to 1 microM had no contractile or relaxant effects on the
      resistance arteries. The three short chain fatty acids alone and in combination,
      however, caused a concentration-dependent (range 0.1-30 mM) relaxation of
      resistance arteries precontracted with 50 mM KCl. This relaxant effect was
      significantly inhibited by the presence of the anion-exchange inhibitor 4,4'
      diisothiocyanatostilbene-2,2'-disulphonic acid whereas it was unaffected by
      removal of the endothelium, presence of indomethacin, propranolol or
      phentolamine. These data suggest that the trophic effects of glutamine and
      epidermal growth factor on the small intestinal mucosa cannot be explained
      through actions on the resistance vasculature. In contrast, the relaxant effect
      of short chain fatty acid on resistance arteries in vitro suggests that these
      compounds may be able to improve the microcirculation in vivo. An improved
      microcirculation will, all things considered, facilitate the growth of the small
      intestinal mucosa.

PMID- 7800662
TI  - Diabetes-induced changes in the Gi-modulated muscarinic receptor-adenylyl cyclase
      system in rat myocardium.
AB  - The inhibitory guanine nucleotide binding regulatory protein (Gi)-mediated
      muscarinic receptor-adenylyl cyclase system was studied in myocardium from adult
      male Wistar rats with 10 weeks of diabetes induced by a single intravenous
      injection of streptozotocin (60 mg/kg). Neither the messenger ribonucleic acid
      level nor the amount of Gi was changed in the streptozotocin diabetic group as
      compared to the control group. The activity of the adenylyl cyclase stimulated by
      guanyliminodiphosphate was decreased by 48% in the streptozotocin diabetic group
      whereas stimulated activities of adenylyl cyclase by sodium fluoride and
      forskolin remained unchanged. The inhibition of forskolin-stimulated adenylyl
      cyclase activity by carbachol was more potent in membranes from the
      streptozotocin diabetic group than that in membranes from the control group. The
      competition binding curve between (3H)- quinuclidinyl benzilate and carbachol
      obtained from the streptozotocin diabetic group was shifted to the left as
      compared to the control group. These results suggest that the myocardium of
      streptozotocin-induced diabetic rats exhibited an increase in Gi function as
      demonstrated by the increased inhibition of guanyliminodiphosphate-mediated
      adenylyl cyclase and the superhigh affinity for carbachol of the muscarinic
      receptors. As there were signs, similar to those seen in clinical heart failure,
      in the streptozotocin diabetic group, these results demonstrate that functional
      alteration of Gi might underlie, at least in part, the cardiac dysfunction that
      is associated with diabetes.

PMID- 7800663
TI  - Fat diet, osmotic fragility of erythrocytes and inotropic response of rat heart
      papillary muscle to noradrenaline stimulation: early appearance of the diet
      effect by lovastatin.
AB  - Intake of lovastatin, an inhibitor of endogenous cholesterol synthesis, leads to
      a compensatory increase in the uptake of cholesterol from plasma (low density
      lipoprotein endocytosis). The drug might exert effects also by facilitating
      uptake of fatty acids carried in low density lipoprotein. It has been reported
      that dietary fat may alter physical properties of erythrocytes as well as
      adrenergic effects in heart muscle. We have therefore studied osmotic fragility
      of erythrocytes and inotropic and lusitropic responses of isolated heart
      papillary muscles taken from rats fed for 3 weeks either a purified high fat diet
      (olive oil/coconut oil 16 g/6 g/100 g diet), prepared plus and minus lovastatin,
      or similar diets in which 4 g/100 g diet of the olive oil was replaced by cod
      liver oil. Three weeks feeding of a high fat diet containing cod liver oil did
      not affect osmotic fragility of erythrocytes or indices of inotropy or lusitropy
      in papillary muscles in response to noradrenaline stimulation neither in the
      absence nor in the presence of lovastatin. In contrast, purified high fat diet
      lacking cod liver oil increased osmotic fragility in a fraction of the
      erythrocytes. When lovastatin was added to this diet the osmotic fragility was
      increased for the whole population of erythrocytes. In this situation the
      "relaxation-onset index"--an index of early relaxation in the papillary muscles-
      was shifted to higher concentrations of noradrenaline. Thus, intake of lovastatin
      may lead to an early appearance of effects of dietary fat on osmotic fragility of
      erythrocytes and on heart muscle responses to catecholamines. These effects of
      lovastatin are, however, apparently dependent upon the kind of dietary fat as
      they are prevented by the presence of cod liver oil.

PMID- 7800664
TI  - Enhanced levels of lipid peroxidation and xanthine oxidase activity in the lung
      of male Sprague-Dawley rats following treatment with O,O,S-trimethyl
      phosphorothioate.
AB  - The purpose of this study was to investigate the roles of lipid peroxidation and
      a prototypical radical generating enzyme, xanthine oxidase, in lung injury caused
      by O,O,S-trimethyl phosphorothioate (OOS-TMP). Animals (five per group) were
      dosed with OOS-TMP at 40 mg/kg and sacrificed on the 1st, 3rd or 7th day after
      treatment. OOS-TMP increased lipid peroxidation (Mean +/- S.E.) to 139 +/- 9.6%
      of the control values in the lung and to 623 +/- 203% in the liver on the 1st
      day. When rats were dosed with OOS-TMP at 20, 40 and 60 mg/kg, lipid peroxidation
      in the lung and the liver were increased in a dose-dependent manner. In the lung,
      the total activity of xanthine oxidase was coincidentally increased. In contrast,
      the activities of superoxide dismutase and catalase were not affected. Effects of
      OOS-TMP on lipid peroxidation and the total activity of xanthine oxidase were
      completely abolished by coadministration with O,O,O-trimethyl phosphorothionate
      of a non-toxic dose (1 mg/kg), which antagonizes the lung injury after treatment
      with OOS-TMP. The present results indicate that free radical formation may be
      involved in lung injury after OOS-TMP treatment through activation of radical
      producing enzymes such as xanthine oxidase.

PMID- 7800665
TI  - Lidocaine interactions with exogenous and endogenous adenosine in the isolated
      rat heart.
AB  - We examined whether pretreatment with lidocaine could influence the cardiac
      kinetics of adenosine and thereby strengthen the physiologic responses of the
      nucleoside, either exogenously administered or endogenously produced. Isolated
      rat hearts perfused with lidocaine, 0.05 microM to 500 microM, were subjected to
      6 min. of adenosine infusion followed by 30 min. of perfusion. The hearts were
      then subjected to 6 min. of total global ischaemia and then perfused for 30 min.
      Effects on cardiac kinetics and physiologic responses of adenosine were based on
      a comparison of uptake or release of adenosine in effluate (kinetics), and the
      effects of adenosine on aortic pressure and left ventricular developed pressure
      (physiologic responses), to a lidocaine-free control group. A low concentration
      of lidocaine, 0.05 microM, increased the uptake of exogenously administered
      adenosine. A high concentration of lidocaine, 50 and 500 microM was associated
      with a reduced release of endogenously produced adenosine. However, these effects
      on cardiac kinetics of adenosine were not associated with any increase of the
      physiologic responses to the nucleoside. The results failed to support the
      hypothesis that lidocaine increases the physiologic responses of adenosine in the
      isolated rat heart by a kinetic interaction.

PMID- 7800666
TI  - The effect of captopril on the oxidation of plasma lipoproteins.
AB  - The antihypertensive drug captopril was found to inhibit the oxidation of low
      density lipoproteins by copper in a dose dependent manner in vitro. Up to 65%
      inhibition of oxidation was observed at the concentration of 100 micrograms/ml of
      captopril. During subsequent studies with patients, captopril protected low
      density lipoproteins against oxidation slightly better than enalapril, although
      this difference was not statistically significant. Captopril had no effect on the
      levels of Lp(a) as compared to the levels established during enalapril treatment.

PMID- 7800667
TI  - Pharmacological comparison of antipsychotic drugs and sigma-antagonists in
      rodents.
AB  - We compared antipsychotic drugs (haloperidol, chlorpromazine and clozapine) and
      sigma antagonists (remoxipride, cinuperone, alpha-(4-fluorophenyl)-4-(-fluoro-2
      pyrimidinyl)-1-piperazine butanol (BMY 14802) and rimcazole) in the radio-ligand
      binding and behavioural experiments in rodents. A good correlation was
      established between the affinity of compounds at dopamine2-receptors in the
      striatum and their ability to block apomorphine-, amphetamine- and quipazine
      induced behavioural effects in rodents. By contrast, no correlation was found
      between the behavioural effects of these drugs and their affinity at dopamine1-5
      HT2- and sigma receptors. The rank order of potency among the studied
      antipsychotic drugs in the behavioural tests and at dopamine2-receptors was
      following: haloperidol >> chlorpromazine > or = clozapine. The effectiveness of
      chlorpromazine and clozapine was nearly similar against apomorphine-induced
      aggressiveness and yawning, whereas at 5-HT2-receptors clozapine was more active
      than chlorpromazine. The weak activity of sigma antagonists at dopamine2
      receptors could be a possible reason why these compounds were less effective in
      the behavioural studies compared to antipsychotic drugs. However, the antagonism
      of remoxipride against apomorphine-induced stereotypy and aggressiveness is not
      related to its activity at sigma receptors, because the other sigma antagonists
      did not block these effects of apomorphine. It is probable that remoxipride
      exerts its action through blocking of dopamine2 receptors. In conclusion, the
      present study revealed only weak activity of sigma antagonists in the behavioural
      models widely used to study the antipsychotic drugs. Therefore, the antipsychotic
      activity of sigma antagonists is doubtful.

PMID- 7800668
TI  - Morphological effects of sodium fusidate (fusidin) on pancreatic islet cells: an
      electron microscopic study.
AB  - Fusidic acid has been shown to prevent the lymphocyte co-stimulatory activities
      of cytokines and seems--in preliminary trials--clinically effective as an
      immunoregulatory drug e.g. in insulin-dependent diabetes mellitus. A toxic effect
      of fusidic acid may however be suspected since a previous study showed a
      significant dilatation of rough endoplasmic reticulum in cultured pancreatic
      islet cells from normal rats. In this study we examined the ultrastructural
      effects of the sodium salt of fusidic acid (fusidin) on cultured rat islet cells
      (treatment period 3-5 days), and of islet cells from rats receiving fusidin for 6
      days. Electron microscopically, fusidin treatment in vitro (3 to 30
      micrograms/ml) showed a significant dilatation of the rough endoplasmic reticulum
      of islet cells. No dose dependent changes were found. In the in vivo model no
      changes were demonstrated in concentrations of fusidin up to 9.64 micrograms/ml
      of homogenated pancreatic tissue. It is concluded that treatment with fusidin
      gives no detectable ultrastructural changes in vivo.

PMID- 7800669
TI  - [Sibling relations: an introduction to the horizontal relation dynamics in a
      psychoanalytic "family" concept].
AB  - This position encompasses the idea that the family concept is represented by a
      vertical, complementary relationship between child and parents. For decades this
      position was hardly disputed. The sibling relationship was set apart, or more
      exactly fixed on a negative, psychopathological potential, in great contrast to
      daily life-experience and to the cultural value-system. This view point (and its
      persistant dominance) is illuminated against the background of multiple
      motivated, collective counterprocesses and deficient, intersubjective development
      theories. A new and clear change that has been taken place in the concept of the
      sibling relationship during the last decade is expounded and discussed here.
      Important conclusions for the development theory are submitted. The sibling
      relationship is, like the parent-child relationship, an elementary experience and
      a transferable behaviour-model. Significant psychodynamic processes in sibling
      relationships are hereby described and possible variant family-dynamics resulting
      from the interplay between the horizontal and vertical levels are outlined. The
      creation of sibling relationships during children's games, of imaginary siblings
      and fantasies of wishing for a sibling are shown. The relevance of the sibling
      dynamics for development processes and for family-dynamic processes thus becomes
      apparent. Important implications for the clinical-psychotherapeutic domain
      reinforce the demand for including the consideration of siblings in the
      psychodynamic discussion of the family and in the clinical setting.

PMID- 7800670
TI  - [Children of psychotic parents--a neglected risk group].
AB  - Children of psychotic parents form a special risk group with an increased
      probability to develop psychiatric disorders. After an introductory presentation
      of the most important research findings, it is shown that, up to now, children of
      psychotic parents have not been paid much attention to in the literature. A
      concept for prevention is introduced that may serve as an orientation for
      planning and realizing preventive measures for children of psychotic parents. The
      prevention program comprises interventions aimed to improve coping strategies
      with the parental psychosis as well as specific preventive interventions to
      improve the situation of the children. Finally, principles are presented that
      should be acknowledged by specialists when doing preventive work.

PMID- 7800671
TI  - [Role of the parents in termination of child psychotherapy].
AB  - This article explores some causes and conditions which can lead to premature
      termination of child psychotherapy. Usually the parents decide about the
      beginning and the end of their child's treatment. Therefore the central issue of
      this paper is the accompanying parent work of child psychotherapy. By presenting
      three casuistic examples the author demonstrates how unconscious wishes and needs
      of the parents can distort their relation to the child and to his therapist. This
      kind of phenomena needs special attention from the therapist in analyzing the
      dynamics of transference and countertransference while working with the parents.
      Otherwise a high risk of premature termination remains, for instance subsequent
      to an unrecognized unconscious arrangement between the therapist and the parents.

PMID- 7800672
TI  - [Therapeutic letters as an intervention in family therapy--exemplified by a case
      of school phobia].
AB  - The paper presents the case of an 11 year old boy with school phobia. As the case
      shows, written interventions in the form of letters can be an added and very
      effective resource of family therapy, that can help to reduce the number of
      family sessions. Despite the added work of writing them they prove to be an
      advantage for the therapist in many ways. One undoubted asset of written messages
      is that--unlike the spoken word--they can be kept and re-read at leisure. They
      also enable the therapist to communicate with family members who avoid the
      sessions.

PMID- 7800673
TI  - [Doppler ultrasound analysis of the pulmonary circulation].

PMID- 7800674
TI  - [Differential diagnosis of alveolitis in systemic diseases].

PMID- 7800675
TI  - [Assessment of intrapulmonary ventilation disorders in children with bronchial
      asthma using the nitrogen elimination technique].
AB  - Stratification of functional abnormalities evaluated by whole-body
      plethysmography in asthmatic children can be characterized into three functional
      groups: pulmonary hyperinflation (H: TGV > mean + 2SD), bronchial obstruction (O:
      Raw > mean + 2SD) and a mixed type, group M, including both abnormalities. The
      multibreath nitrogen washout (MBNW) offers the possibility to measure FRC and
      calculate the amount of trapped gases (TG = TGV-FRCMBNW). Furthermore ventilation
      inequalities can be estimated by mathematical analysis of the washout curve from
      which indexes such as the lung clearance index (LCI), the mean dilution number
      (MDN) and the moment ratio (m2:m0 = M-ratio) can be obtained. In 69 asthmatic
      children (age 5-17 y; 38 boys, 31 girls) body plethysmography and MBNW were
      performed in the symptom free interval. The questions were, at what extend TG are
      present within the different functional groups, and which parameters best
      describe ventilation inequalities. The group attribution was H: 23, M: 16, O: 30.
      The highest amount of TG was found in H (36.4 +/- 22.2% TGV), then in M (26.6 +/-
      23.1% TGV) and in O (19.4 +/- 16.0% TGV). In 33/50 cases presenting with normal
      TGV, TG mainly was at cost of a low FRC (13 in H, 8 im M, 12 in O). In 19 cases
      FRC was higher than TGV (3 in H, 1 in M 15 in O). TG was closely related with
      LCI, MDN and M-ratio. Most pronounced ventilation inequalities were found in
      group M showing a correlation only with FRC, but not with TGV.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7800676
TI  - [Diagnosis, therapy and prognosis of atypical mycobacterial infections--results
      of a retrospective study].
AB  - The most important mycobacteria causing disease in humans are Mycobacterium
      tuberculosis and Mycobacterium leprae. These germs contrast the so-called
      atypical mycobacteria. The importance of the atypical mycobacteria was recognized
      in the fifties. Even if the quantity of atypical mycobacterial disease has
      increased during the last decades in Germany, it is still a rare disease today,
      but it is seen in patients with acquired immunodeficiency syndrome more often
      nowadays. In the period from 1st January 1986 til 31st December 1992 31 HIV
      negative patients with a diagnosis of atypical mycobacterial disease have been
      seen in the department for lung diseases in the Thoraxklinik Heidelberg-Rohrbach.
      During the same period an atypical mycobacterial disease was diagnosed in 12 out
      of 413 HIV-positive patients (2.9%) of the AIDS-ambulance of the skin hospital of
      the University of Heidelberg. Most of the HIV-negative patients showed additional
      diseases which reduce the immunological resistance. In HIV-positive patients an
      atypical mycobacteriosis heralds a severe immunodeficiency. Because it is a rare
      disease and an exact diagnosis is difficult to establish there is a lack of
      controlled clinical trials and therefore detailed therapeutical guidelines do not
      exist. A therapeutical approach is also complicated by a lack of effective drugs.
      With disseminated disease in AIDS-patients, which is mostly caused by
      Mycobacterium avium-intracellulare, the therapy should be stopped, if there are
      any severe side-effects. The present results of therapy are still disappointing.
      In the future the management of atypical mycobacterial disease will be more
      important, because there is an increasing number of patients with acquired
      immunodeficiency.

PMID- 7800677
TI  - [Cytochemical studies for determining the histogenesis of anaplastic and poorly
      differentiated lung tumors].
AB  - Proper histogenetic classification of pulmonary tumours is most important in
      choosing the best possible treatment. Since this is very difficult especially in
      case of anaplastic or poorly differentiated tumours, additional pointers on
      histogenesis, supplied by complementary histochemical examinations, are very
      helpful. 105 bronchial carcinomas were examined cytochemically by means of air
      dried smear preparations (imprint, brush an puncture smears). Cytochemical
      examinations were performed in respect of alkaline phosphatase, acid phosphatase,
      PAS reaction and unspecific esterase. It was found that the dedifferentiated
      squamous cell carcinomas were alkaline phosphatase-negative and weakly positive
      to acid phosphatase and unspecific esterase, whereas dedifferentiated
      adenocarcinomas were strongly positive to acid phosphatase and unspecific
      esterase. The PAS reaction was always slightly to moderately positive. Small-cell
      bronchial carcinomas were negative in all cytochemical examinations.

PMID- 7800678
TI  - [Manifestation of lung tuberculosis as soft tissue tumor (gravitation abscess in
      mediastinal lymphadenitis) of the thoracic wall in a 32-year-old woman].
AB  - In a 32-year-old female appeared after a period of weeks with pain in the back
      and left flank a tumor (8 x 6 cm in size) in the anterior axillary line (9.-11.
      rib). The patient was afebril and in good condition. X-rays and Contrast-CT
      findings showed round shaped infiltrations in both upper lobes of the lung,
      widening of the mediastinum (right paratracheal) and left pleural effusion. The
      mediastinal mass showed "rim enhancement" and "central low density areas", which
      is typical for liquefaction of caseous material in tuberculous lymphadenitis and
      gravitation abscess. The tumor was resected incompletely, because there was
      connection to the 8. intercostal space. In the cross-section the tumor appeared
      grey-white, histologically there was caseous material surrounded by epitheloid
      cells and Langhans giant cells, as to see in tuberculous gravitation abscess.
      Ziehl-Neelsen-staining of resected material and bronchial secret was negative,
      but of both specimen Mycobacterium tuberculosis was cultured. The patient got a
      therapy with INH, Ethambutol, Pyrazinamid and Rifampicin. Regression of the
      parenchymal fokus and the mediastinal lymphadenitis was observed.

PMID- 7800679
TI  - T-lymphocyte dysregulation in asthma.
AB  - In this paper, we have reviewed the evidence suggesting that T-cell dysregulation
      is important in the pathogenesis of asthma. The history, clinical presentation,
      and an overview of the appropriate management of asthma have been briefly
      reviewed. T cells obtained from the airways of asthmatics display signs of
      activation; these changes mirror the intramural inflammation found at biopsy.
      There is debate about the importance of T helper/suppressor ratios in this
      population of cells, but alterations in these ratios have been noted with
      experimental allergen exposure, as well as during acute asthma attacks; some of
      these changes revert toward normal with steroid therapy. The division of T helper
      lymphocytes into Th1 and Th2 cells, first described in studies of murine
      immunology, appear to be relevant in humans, particularly in allergic disease.
      Although IL-4 and IL-5, prototypical Th2 cytokines, have been most clearly
      implicated in asthma, there is some evidence supporting a role for Th1
      cells/cytokines as well.

PMID- 7800680
TI  - Gender differences in adrenal cortex steroid production in SHR/N-corpulent rats.
AB  - Gender differences in adrenal steroid hormone production and serum steroid
      hormone levels were compared in the spontaneous hypertensive/NIH-corpulent (cp)
      rat, which exhibits characteristics of both obesity and non-insulin-dependent
      diabetes mellitus. The study demonstrated that adrenal gland size correlated with
      adrenal production and serum levels of steroid hormones. Obese female SHR/N-cp
      rats were more steroidogenic than male SHR/N-cp rats; the size of their adrenal
      glands was twice that of the males (70 vs 33 mg). Body weights averaged 666 g for
      females and 829 g for males. Obese female rats had significantly higher serum
      concentrations of both corticosterone (827 vs 536 ng/ml) and aldosterone (675 vs
      482 pg/ml) than obese male rats. As determined by in vitro assay, adrenal cortex
      production of corticosterone (2157 vs 1435 ng/30 min) and aldosterone (13.3 vs
      9.5 ng/30 min) was significantly higher in obese female than in obese male rats.
      Adrenal production of testosterone in the in vitro assay was also significantly
      higher for obese female than male rats; however, adrenal estrogen production in
      obese rats did not differ significantly. The type of carbohydrate consumed
      (sucrose > starch) significantly affected serum levels of corticosterone, but not
      aldosterone, testosterone, or estrogen. Gender differences in adrenal steroid
      production and serum steroid levels suggest that hyperglycemia in obese SHR/N-cp
      rats may be, in part, the result of excess adrenal production of steroid
      hormones.

PMID- 7800681
TI  - Early treatment of obese (ob/ob) mice with triiodothyronine increases oxygen
      consumption and temperature and decreases body fat content.
AB  - An early abnormality in the ob/ob mouse is a low circulating level of the thyroid
      hormone, triiodothyronine (T3). The possibility was explored that early T3
      treatment of ob/ob mice will increase oxidative metabolism and lower body fat
      content. Doses of T3, ranging from 0.0 to 25.0 micrograms/100 g body wt were
      injected, ip, into ob/ob and non-ob/ob mice daily from 3 weeks until 6 weeks of
      age. Food intake was equalized across all groups to that consumed by non-ob/ob
      saline-treated group. At 6 weeks of age, body weight, serum concentrations of
      thyroxine (T4), T3, insulin and glucose, oxygen consumption, colonic temperature,
      and body composition were analyzed. T3 treatment decreased body weight, increased
      body oxygen consumption, increased colonic temperature, and decreased body fat
      without a significant change in body protein in ob/ob mice. T3 treatment also
      increased serum T3, and decreased serum T4, insulin, and glucose concentrations
      in ob/ob mice. Because total body protein did not change as a result of T3
      treatment, the increased oxidative metabolism due to T3 treatment was probably
      via the change of metabolic activity of the total lean body mass or the specific
      metabolically active tissues in the ob/ob mice, such as brown adipose tissue,
      liver, or muscle.

PMID- 7800682
TI  - Altered interleukin-2 production by lymphocyte populations from bovine leukemia
      virus-infected cattle.
AB  - The effects of bovine leukosis virus (BLV) on the phenotypic and functional
      characteristics of peripheral blood mononuclear cells were investigated. Whole
      blood differentials showed that persistently lymphocytotic (BLV+PL) dairy cattle
      had more lymphocytes and fewer neutrophils than the aleukemic seropositive
      (BLV+AL) or seronegative (BLV-) animals. Flow cytometric analyses of peripheral
      blood mononuclear cells indicated that the BLV+PL animals had more B lymphocytes,
      with a concomitant decrease in CD2 positive cells when compared with the BLV-
      group. Mononuclear cells from the BLV+AL animals also had fewer CD2 positive
      cells, but no differences in B lymphocytes were observed when compared with BLV-
      cattle. Peripheral blood mononuclear cells were used in blastogenesis assays to
      assess the functional ability of lymphocytes. Lymphocytes from BLV+PL animals had
      lower proliferative responses to concanavalin A and pokeweed mitogen when
      compared with cells from the BLV- or BLV+AL groups. The level of spontaneous
      blastogenesis in the absence of mitogenic stimulation was high for lymphocytes
      obtained from BLV+AL cattle. Cultures of lymphocytes obtained from BLV+PL animals
      produced greater amounts of interleukin-2 (IL-2) than BLV+AL and BLV- groups,
      although no differences were observed in the expression of IL-2 receptors. The
      development of uncontrolled lymphocytosis in BLV-infected cattle may result from
      an altered responsiveness to IL-2-regulated B-lymphocyte proliferation.

PMID- 7800683
TI  - Inhibitory effect of Bifidobacterium longum cultures on the azoxymethane-induced
      aberrant crypt foci formation and fecal bacterial beta-glucuronidase.
AB  - Epidemiologic and experimental studies suggest that consumption of fermented milk
      products and lactic bacterial cultures that are used to ferment the dairy
      products, decrease the incidence of certain types of cancer. The present study
      was designed to determine the effect of lyophilized cultures of Bifidobacterium
      longum (B. longum), a lactic bacteria, on the azoxymethane (AOM)-induced
      preneoplastic lesions such as aberrant crypt foci (ACF) formation in the colon
      and on fecal bacterial beta-glucuronidase activity in male F344 rats. At 5 weeks
      of age, groups of animals were fed the AIN-76A (control) and the experimental
      diets containing 1.5% and 3% lyophilized cultures of B. longum. At 10 weeks of
      age, all animals received sc injection of AOM dissolved in normal saline at a
      dose rate of 20 mg/kg body wt, once weekly for 2 weeks. The animals were
      necropsied 6 weeks after the last AOM injection, and the ACF were visualized
      under light microscopy in the formalin-fixed, unsectioned methylene blue-stained
      colons where they were distinguished by their increased size, more prominent
      epithelial cells, and pericryptal space. The cecal contents were analyzed for
      bacterial beta-glucuronidase activity. The feeding of lyophilized cultures of B.
      longum significantly inhibited the ACF formation (53%) and the crypt multiplicity
      in the colon. A significant decrease in the fecal bacterial beta-glucuronidase
      was also observed in the animals fed the diets containing Bifidobacterium
      supplements as compared with control diet. These results demonstrate that B.
      longum in diet influences the metabolic activity of certain types of intestinal
      microflora that are involved in the production of beta-glucuronidase.
      Furthermore, the findings also suggest that B. longum supplements inhibit ACF
      formation, an early preneoplastic marker of malignant potential in the process of
      colon carcinogenesis.

PMID- 7800684
TI  - Protein kinase C and intracellular free Ca++: relationship to human
      immunodeficiency virus (HIV)-induced cellular hyporesponsiveness.
AB  - Protein Kinase C (PKC) and Ca++ are both involved in the chain of events leading
      to T-cell activation. An impairment of the immune response is characteristic of T
      cells obtained from patients with HIV infection. In this report, the involvement
      of PKC and Ca++ in HIV-mediated cellular hyporesponsiveness was examined.
      Infection of peripheral blood mononuclear cells (PBMC)s from HIV-seronegative
      normal donors with HIV strain HTLV IIIB, or two fresh patient isolates produced a
      1.4-, 10.7-, and 11.4-fold enhancement in PKC activity at 1 hr postinfection (PI)
      and a 1.8-, 2.3-, and 3.8-fold enhancement at 12 hr PI, respectively. A marked
      decrease of PKC content, as determined by Western Blot analysis, was observed in
      HIV-infected cells by Day 4 and 7 PI compared with mock-infected control cells.
      Furthermore, PKC synthesis was also inhibited in cells from immunosuppressed AIDS
      patients. PKC activity of PBMCs from HIV-infected patients did not change in
      response to 1 microM of phorbal myristate acetate (PMA). In contrast, the same
      dose enhanced the activity by 50%-100% in PBMCs from normal HIV-seronegative
      donors. A 40%, 50%, and 125% increase in intracellular free Ca++ in response to
      HIV infection was observed 12 hr PI in MT4, JURKAT, and PBMCs, respectively.
      However, the increase in intracellular free Ca++ in HIV-infected PBMCs obtained
      from normal donors in response to PHA was 56% and 17% compared with an increase
      of 100% and 120% in mock infected cells at 12 hr and 1 week PI, respectively.
      Comparing the Ca++ response to PHA in PBMCs from HIV-infected patients showed
      that patients with < 250 absolute T4 cells/mm3 had an impaired Ca++ response.
      These data suggest that there is a relationship between intracellular free Ca++
      and PKC and HIV-induced T-cell hyporesponsiveness.

PMID- 7800685
TI  - Nicotine increases [Ca2+]i in rat sublingual mucous acini by stimulating
      neurotransmitter release from presynaptic terminals.
AB  - The effects of nicotine on the intracellular free Ca2+ concentration ([Ca2+]i)
      were examined using the Ca(2+)-sensitive fluorescent dyes indo-1 and fura-2 in
      isolated rat sublingual mucous acini. Nicotine induced a dose-dependent increase
      in [Ca2+]i. In contrast to the muscarinic agonist carbachol-induced rise in
      [Ca2+]i, the nicotine-stimulated increase was abolished in a Ca(2+)-free medium,
      in the presence of L-type Ca2+ channel blockers (diltiazem and D888), by
      depolarization (high extracellular K+), and if the intracellular Ca2+ pool was
      first depleted with thapsigargin, an endoplasmic Ca(2+)-ATPase inhibitor.
      Furthermore, inhibitors of the nicotine acetylcholine receptor (mecamylamine,
      decamethonium, hexamethonium, tubocurarine, and alpha-bungarotoxin) blocked the
      nicotine-stimulated increase in [Ca2+]i without affecting the muscarinic
      stimulated [Ca2+]i increase, whereas, muscarinic antagonists (atropine,
      pirenzepine and 4-diphenylacetoxy-N-methylpiperidine methiodide [4-DAMP])
      inhibited both the nicotine- and carbachol-induced [Ca2+]i increases. Nicotine
      stimulation increased inositol 1,4,5-trisphosphate (IP3) content by 50%.
      Inhibition of the IP3-sensitive intracellular Ca2+ release pathway with 8
      (diethylamino)-ocytl-3,4,5-trimethoxybenzoate (TMB-8) prevented the nicotine
      induced increase in [Ca2+]i. Confocal imaging of [Ca2+]i indicated that the
      nicotine-induced and the carbachol-induced increases in [Ca2+]i occurred in the
      same cells within an acinus. However, in single sublingual acinar cells nicotine
      did not increase [Ca2+]i, whereas, carbachol did. Taken together, these results
      suggest that nicotine first triggers the release of acetylcholine from
      presynaptic nerve terminals associated with the dispersed sublingual acini which
      then activates muscarinic receptors.

PMID- 7800686
TI  - Copper deficiency increases cytochrome P450-dependent 7-ethoxyresorufin-O
      deethylase activity in rat small intestine.
AB  - Although impaired heme synthesis during copper deficiency may limit the
      production and function of hemoproteins, little is known about the effects of
      copper deficiency on the cytochromes P450, an important family of hemoproteins,
      in the small intestine. A series of experiments was conducted to examine the
      effects of copper deficiency on cytochrome P450 content, ethoxyresorufin-O
      deethylase (EROD) activity, and NADPH-cytochrome P450 reductase activity in rat
      small intestine. Sixteen hours after a single oral administration of 5,6
      benzoflavone (BF), an inducer of cytochromes P4501A1 and P4501A2, intestinal
      cytochrome P450 content was elevated as indicated by the CO-difference spectrum
      of the reduced cytochrome and by immunoblotting using anticytochrome P4501A1/1A2.
      However, cytochrome P450 content, measured by either method following BF
      induction, was not affected by copper deficiency. Thus, copper deficiency did not
      impair the availability of heme for cytochrome P450 synthesis in the small
      intestine. Even though copper deficiency did not affect intestinal cytochrome
      P450 content, EROD activity, which is a cytochrome P450-associated monooxygenase
      activity, was 9-fold higher in copper-deficient rats compared with controls
      following BF treatment. The finding that copper deficiency has no effect on
      intestinal cytochrome P450 content suggests that the increased EROD activity
      results from an effect of copper deficiency on the cytochrome P450 reductase
      component of the monooxygenase system. Measurement of cytochrome P450 reductase
      activity showed a 2-fold increase in the small intestines of copper-deficient
      rats compared with controls. It is possible, therefore, that increased intestinal
      cytochrome P450 reductase activity during copper deficiency increases EROD
      activity by facilitating the flow of electrons to cytochrome P450 during the
      redox cycle that cytochrome P450 undergoes during the O-deethylation of
      ethoxyresorufin.

PMID- 7800687
TI  - Intestinal oxygen uptake and glucose metabolism during nutrient absorption in the
      pig.
AB  - Intestinal transport of nutrients coincides with their partial catabolism in the
      gut. The aim of the present study was to measure intestinal oxygen consumption
      and nutrient metabolism after a meal or during a short fast. Nutrient and oxygen
      balances across the small intestine were measured in conscious 50 kg (live wt)
      pigs. Jejunal enterocytes were also isolated from 1-hr postprandial,
      postabsorptive, or 3-day fasted pigs, in order to evaluate their capacities to
      metabolize 5 mM glucose and 2 mM glutamine. Whatever the nutritional state,
      intestinal oxygen consumption was high, since 26 +/- 2% (n = 6) of the oxygen
      arterial supply was extracted by the small intestine. Furthermore, the
      consumption of a mixed meal induced a rapid and transient rise in oxygen
      consumption. In the postabsorptive state, the intestinal uptake of glucose (0.31
      +/- 0.08 mmole/min, n = 6) was twice higher than that of glutamine. The role of
      glucose as a fuel was also evidenced after a 3-day fast. During nutrient
      absorption, glutamine was highly utilized, and lactate was produced. The capacity
      of enterocytes isolated from fed pigs to metabolize glucose was dramatically
      reduced, as was 6-phosphofructo 1-kinase activity. In contrast, intestinal muscle
      presented a high glycolytic capacity from glucose, suggesting that the main site
      of intestinal lactate production during nutrient absorption would be the muscular
      rather than the epithelial layer.

PMID- 7800689
TI  - Evidence that fibronectin-immunoglobulin complexes occur normally in plasma.
AB  - This study was done to ascertain whether complexes of plasma fibronectin (PFn)
      and immunoglobulins (Igs) are normally present in plasma. PFn preparations from
      plasmas of six random human donors were analyzed for IgG, IgM, and IgA by
      competitive ELISA procedures. To look for direct evidence of circulating
      complexes, two of the plasma samples were chromatographed on Sephacryl S-300. PFn
      prepared from a pool of three plasmas by cryoprecipitation was studied by crossed
      immunoelectrophoresis to detect PFn-Ig complexes. The Ig content of PFn ranged
      from 0.78% to 9.0% IgG; 0.25% to 4.9% IgM, and 0.15% to 0.71% IgA. The relative
      amounts were IgG > IgM > IgA in every sample, but the total Ig content of PFn
      varied with the plasma donor. The Sephacryl S-300 chromatogram of the plasma from
      which Ig-rich PFn was made showed distortion of the PFn peak by Ig peaks. PFn
      prepared by cryoprecipitation contained PFn-immunoglobulin complexes. Plasma from
      adult beagle dogs was used to prepare canine PFn. IgM was detected in canine PFn
      by SDS-Page and by double diffusion experiments against antiserum to canine IgM.
      By crossed immunoelectrophoresis, a PFn-IgM complex was detected in canine
      plasma. The cryoprecipitate recovered from a Sephacryl S-300 chromatogram of
      canine plasma contained equivalent amounts of IgM and PFn. These data suggest
      that complexes of Igs with PFn are normally present in plasma.

PMID- 7800688
TI  - Activation of SH2-containing proteins by insulin in proliferating mouse parotid
      gland acinar cells.
AB  - Chronic treatment of mice with insulin results in hypertrophy and hyperplasia of
      the parotid and submandibular glands (Wang et al.: 1994, Proc Soc Exp Biol Med
      205:353-361). Hyperplasia of the parotid gland is mediated by the elevation of
      tyrosine phosphorylation of phospholipase C gamma, p21ras-GTPase activating
      protein (p21ras-GAP) and phosphatidylinositol 3-kinase. These proteins were found
      to be associated with the insulin receptor substrate-1 most likely through src
      homology (SH2) domains of these proteins. There was also a transient increase in
      intracellular cAMP and protein kinase A during the first day of treatment which
      declined by Day 3 to near control values. Protein kinase C activity, on the other
      hand, remained elevated for the 3-day injection regimen. Thus, acinar cell
      proliferation induced by insulin requires activation of many of the same
      signaling components as other tyrosine kinase possessing growth factor receptors.

PMID- 7800690
TI  - Intermittent self-catheterisation--the key facts.
AB  - 1. There is a lack of knowledge among health professionals about intermittent
      self-catheterisation. 2. The technique has improved quality of life for many
      people suffering from continence problems. 3. Intermittent self-catheterisation
      has many advantages over the use of permanent indwelling catheters.

PMID- 7800691
TI  - A mark of approval. Patient satisfaction with an i.v. self-infusion teaching
      programme.
AB  - 1. Self-infusion of IV immunoglobulin at home has many advantages for patients
      and their partners/carers. 2. To operate safely, home therapy programmes must
      include sufficient patient teaching and support. 3. Established home therapy
      patients were questioned on the service provided for them. 4. Overall, the
      service provided is perceived to be very good.

PMID- 7800692
TI  - A common language for a common strategy. Information management and technology in
      the NHS.
AB  - 1. Accurate, timely and comprehensive clinical information is essential for
      ensuring high quality, cost-effective patient care. 2. Improved basic information
      is a basic requirment at all levels in the NHS if it is to respond to new
      challenges. 3. A major aim of the NHS information strategy is to develop a common
      infrastructure across the service. 4. Effective and efficient sharing of clinical
      information among healthcare professionals can only be possible by way of a
      common language of health.

PMID- 7800693
TI  - Careful planning ensures a happy outcome. Caring for pregnant women with
      diabetes.
AB  - 1. It is essential that women with diabetes are offered pre-pregnancy counselling
      and a shared plan of care during their pregnancy. 2. Care of pregnant women with
      diabetes is best offered by the multidisciplinary team. 3. Education is a vital
      part of care. 4. Motivation is strong in pregnancy, and health professionals must
      aim to maintain it.

PMID- 7800694
TI  - Understanding transdermal medication.
AB  - 1. The use of the skin as a route of drug delivery is becoming increasingly
      popular. 2. Transdermal medication combines the relative ease of oral medication
      with many of the advantages of IV administration. 3. Nurses must understand
      transdermal medication in order to help and advise their clients about this form
      of treatment.

PMID- 7800695
TI  - Study that suits your schedule: using the Professional Nurse Accredited Learning
      Scheme.

PMID- 7800696
TI  - Where intuition and opinion rule supreme: psychiatric nurses' knowledge of and
      attitude to HIV and AIDS.

PMID- 7800697
TI  - 'Special care' in the community role of the community neonatal liaison sister.
AB  - 1. It is essential that a relationship is forged between the CNLS and parents
      while the baby is in the SCBU. 2. Following discharge, the emphasis of caring
      changes from the baby to the parents. 3. The role of the CNLS, is everchanging,
      as it adapts to the needs of parents.

PMID- 7800698
TI  - In the patient's best interests? Dehydration in dying patients.
AB  - 1. Little is known about the physiological effects of dehydration in terminally
      ill patients. 2. Terminally ill patients in hospices are not usually given IV
      infusions. 3. Dying patients not given artificial hydration are less likely to
      need suction. 4. Hydrating dying patients may add to their distress.

PMID- 7800699
TI  - Foresight that leads to improved outcome: stoma care nurses' role in siting
      stomas.
AB  - 1. It is essential that all stomas, whether routine or emergency, are properly
      sited. 2. In assessing the siting of stomas, it is vital to review clinical
      practice. 3. Incorrect siting has serious consequences for the patient's
      physical, social and emotional wellbeing. 4. It is essential that nurses and
      surgeons work together to achieve successful patient outcomes.

PMID- 7800700
TI  - A time and money saver? Cost comparison of i.v. therapy with and without Pall 96
      filters.
AB  - 1. Nurses should not be adverse to performing their own research projects to
      inform their clinical practice. 2. Intravenous filters can reduce the risks
      involved in IV therapy from microbes, particulates or air, and reduce the
      incidence of phlebitis. 3. Use of Pall 96 filters may be cost-effective in
      general medical wards, but this study was too small for general application.

PMID- 7800701
TI  - Human papilloma virus type 18 DNA immortalized cell lines from the human prostate
      epithelium.

PMID- 7800702
TI  - Design and analysis of chromosome physical mapping experiments.
AB  - Mathematical and statistical aspects of constructing ordered-clone physical maps
      of chromosomes are reviewed. Three broad problems are addressed: analysis of
      fingerprint data to identify configurations of overlapping clones, prediction of
      the rate of progress of a mapping strategy and optimal design of pooling schemes
      for screening large clone libraries.

PMID- 7800703
TI  - Linkage analysis: progress and problems.
AB  - Linkage analysis involves identifying the locations of genes responsible for
      disease by identifying other genes that co-segregate through families with the
      risk of disease. Subsequently, molecular approaches are applied to find the
      precise gene involved. Although these approaches have been successful to date,
      applications to diseases which do not show clear Mendelian inheritance have
      presented problems. The nature of these problems is discussed.

PMID- 7800704
TI  - Monte Carlo likelihood in the genetic mapping of complex traits.
AB  - Many of the likelihoods arising in the analysis of complex genetic traits,
      particularly in linkage analysis, are computationally infeasible. Where exact
      likelihoods cannot be computed, Monte Carlo estimates of likelihoods may provide
      a satisfactory alternative. Although simulation on pedigrees is straightforward,
      simulation conditional upon observed phenotypic data is not. However, recent
      advances in Markov chain Monte Carlo methods have provided a method well suited
      to this problem. From realizations of underlying genes, simulated under a genetic
      model, conditional upon observed data, a Monte Carlo estimate of this likelihood
      surface can be formed. Various sampler and model modifications are needed to
      enhance the statistical efficiency of the Monte Carlo estimator; as these methods
      become increasingly developed, this approach becomes a useful tool in resolving
      the genes contributing to the phenotypes associated with genetically complex
      diseases.

PMID- 7800705
TI  - Artificial intelligence in molecular biology: a review and assessment.
AB  - Over the past ten years, molecular biologists and computer scientists have
      experimented with various computational methods developed in artificial
      intelligence (AI). AI research has yielded a number of novel technologies, which
      are typified by an emphasis on symbolic (non-numerical) programming methods aimed
      at problems which are not amenable to classical algorithmic solutions. Prominent
      examples include knowledge-based and expert systems, qualitative simulation and
      artificial neural networks and other automated learning techniques. These methods
      have been applied to problems in data analysis, construction of advanced
      databases and modelling of biological systems. Practical results are now being
      obtained, notably in the recognition of active genes in genomic sequences, the
      assembly of physical and genetic maps and protein structure prediction. This
      paper outlines the principal methods, surveys the findings to date, and
      identifies the promising trends and current limitations.

PMID- 7800706
TI  - Application of machine learning to structural molecular biology.
AB  - A technique of machine learning, inductive logic programming implemented in the
      program GOLEM, has been applied to three problems in structural molecular
      biology. These problems are: the prediction of protein secondary structure; the
      identification of rules governing the arrangement of beta-sheets strands in the
      tertiary folding of proteins; and the modelling of a quantitative structure
      activity relationship (QSAR) of a series of drugs. For secondary structure
      prediction and the QSAR, GOLEM yielded predictions comparable with contemporary
      approaches including neural networks. Rules for beta-strand arrangement are
      derived and it is planned to contrast their accuracy with those obtained by human
      inspection. In all three studies GOLEM discovered rules that provided insight
      into the stereochemistry of the system. We conclude machine learning used
      together with human intervention will provide a powerful tool to discover
      patterns in biological sequences and structures.

PMID- 7800707
TI  - The recognition of protein structure and function from sequence: adding value to
      genome data.
AB  - The explosion of DNA sequence data from genome projects presents many challenges.
      For instance, we must extend our current knowledge of protein structure and
      function so that it can be applied to these new sequences. The derivation of
      rules for the relationships between sequence and structure allow us to recognize
      a common fold by the use of tertiary templates. New techniques enable us to begin
      to meet the challenge of rule-based modelling of distantly related proteins. This
      paper describes an integrated and knowledge-based approach to the prediction of
      protein structure and function which can maximize the value of sequence
      information.

PMID- 7800708
TI  - Estimating statistical significance of sequence alignments.
AB  - Algorithms that compare two proteins or DNA sequences and produce an alignment of
      the best matching segments are widely used in molecular biology. These algorithms
      produce scores that when comparing random sequences of length n grow proportional
      to n or to log(n) depending on the algorithm parameters. The Azuma-Hoeffding
      inequality gives an upper bound on the probability of large deviations of the
      score from its mean in the linear case. Poisson approximation can be applied in
      the logarithmic case.

PMID- 7800709
TI  - Statistical studies of biomolecular sequences: score-based methods.
AB  - The massive accumulation of DNA and protein sequence data poses challenges and
      opportunities in terms of interpretation and analysis. This presentation reviews
      the method of score-based sequence analysis with the objectives of discerning
      distinctive segments in single sequences and identifying significant common
      segments in sequence comparisons. A number of new results are described here for
      both the theory and its applications. These include distributional theory
      involving several high scoring segments in single sequences, distribution
      formulas for general scoring regimes in multiple sequence comparisons, bounds for
      periodic scoring assignments, sensitivity analysis of genome composition and
      refinements on predicting exons and genes in DNA sequences.

PMID- 7800710
TI  - Sampling theory for neutral alleles in a varying environment.
AB  - We develop a sampling theory for genes sampled from a population evolving with
      deterministically varying size. We use a coalescent approach to provide
      recursions for the probabilities of particular sample configurations, and
      describe a Monte Carlo method by which the solutions to such recursions can be
      approximated. We focus on infinite-alleles, infinite-sites and finite-sites
      models. This approach may be used to find maximum likelihood estimates of
      parameters of genetic interest, and to test hypotheses about the varying
      environment. The methods are illustrated with data from the mitochondrial control
      region sampled from a North American Indian tribe.

PMID- 7800711
TI  - Molecular evolution of serine protease and its inhibitor with special reference
      to domain evolution.
AB  - The evolution of serine protease and its inhibitor are discussed with special
      reference to domain evolution. It is now known that most proteins are composed of
      more than one functional domain. Because serine proteases such as urokinase and
      plasminogen are made of various functional domains, these proteins are typical
      examples of the so-called mosaic proteins. When Kringle domains in serine
      proteases and a Kunitz-type protease inhibitor domain in the amyloid beta
      precursor protein in Alzheimer's disease patients were examined by the molecular
      evolutionary analysis, the phylogenetic trees constructed showed that these
      functional domains had undergone dynamic changes in the evolutionary process. In
      particular, these domains are evolutionarily movable. Thus, it is concluded that
      various functional domains evolved independently of each other and that they have
      been shuffled to create the existent mosaic proteins. This conclusion leads us to
      the reasonable speculation that those functional domains must have been minigenes
      possibly at the time of primordial life or the origin of life. We call these
      minigenes 'ancestral minigenes'. Every effort should be made to answer the
      question about the minimum set of ancestral minigenes that must have existed and
      must have been needed for maintaining life forms. The DNA sequence database is
      useful for making attempts to answer such difficult but significant questions.

PMID- 7800712
TI  - Photophysical study of the Schiff bases of 5'-deoxypyridoxal and n-hexylamine in
      cationic micelles.
AB  - The absorption and fluorescence spectra of the Schiff bases formed between 5'
      deoxypyridoxal and n-hexylamine in aqueous media containing different
      concentrations of the cationic surfactant hexadecyltrimethylammonium bromide were
      recorded at 25 degrees C. The quantum yields of fluorescence of the different
      zwitterionic and enol forms of the chemical species of the Schiff bases occurring
      in media of pH 4.5-8.5 were determined. Also, the fluorescence quenching
      resulting from the presence of the surfactant and that of iodide ion were
      analyzed. From the results obtained it follows that the zwitterionic forms do not
      interact with the cationic surfactant, whereas the enol forms do interact with
      it.

PMID- 7800713
TI  - Visible chemiluminescence associated with the reaction between methemoglobin or
      oxyhemoglobin with hydrogen peroxide.
AB  - Visible chemiluminescence is emitted in the irreversible deactivation of
      hemoglobin or methemoglobin with excess H2O2. The emission takes place in two
      phases. The most intense one lasts a few seconds and is followed by a second
      phase of lower intensity that remains for longer periods. This second phase
      presents chaotic or sustained oscillations. Free radicals are implicated in the
      luminescent process since the emission can be reduced by free radical scavengers
      such as 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox) or
      ascorbic acid. These additives lead to a delay in reaching the maximum intensity,
      which can be related to their consumption, implying substantial recycling of the
      hemoprotein. Chemiluminescence is also observed in the oxidation of hemin by
      H2O2, suggesting a role for the heme group in the processes leading to the
      excited state production. The lower intensity observed in the presence of hemin
      can be related to the contribution of the globin chains.

PMID- 7800714
TI  - ArF excimer laser-induced bubble formation during irradiation of NaCl solutions.
AB  - During application of the 193 nm excimer laser to vitreoretinal surgery, very
      deep cutting of the retina of about 100 microm/pulse was detected at the energy
      fluence in the range of 0.25-0.35 J/cm2/pulse. At the surface of the ablating tip
      insoluble bubbles were observed during the irradiation. In this paper we study
      production of these bubbles in aqueous solutions of sodium chloride. The yield of
      gaseous photoproducts was measured as a function of NaCl concentration and energy
      fluence. At concentrations of 100 g/L powerful water vapor bubbles and shock
      waves were observed. A mechanism of soft tissue cutting by the 193 nm laser in
      highly absorbing liquid media is suggested that explains the features of
      vitreoretinal ablation with this system: (1) the high cutting depth when the tip
      touches the tissue and (2) the absence of cutting when the tip is not in contact
      with tissue. The advantages of the ArF laser for microsurgery of internal organs
      are discussed.

PMID- 7800715
TI  - Spectroscopy and photosensitization of sapphyrins in solutions and biological
      membranes.
AB  - A spectroscopic and photophysical study of three new sapphyrin molecules is
      presented. The sapphyrin backbone that was derivatized to make them water soluble
      possesses an absorption band around 700 nm, a desired property for biological
      photosensitization. We studied the absorption and fluorescence spectra, from
      which evidence for aggregation in solvents of different polarities was obtained.
      The extent of aggregation is correlated with the nature of the attached moiety.
      The absolute quantum yields of singlet oxygen production were measured, with 1,3
      diphenyl isobenzofuran as a model target, and were 0.13-0.18 in ethanol. The
      binding constants to liposomes and to cells were determined spectroscopically and
      were found to correspond to the hydrophobicities of the compounds, with an
      additional effect, ascribed to the sugar moiety, which was found in the case of
      one of the sapphyrins. The efficiency of photodamage to Staphylococcus aureus by
      sapphyrins and hematoporphyrin was equivalent, on the basis of cells killed per
      microgram of sensitizer in the incubation mixture.

PMID- 7800716
TI  - Photochemistry of 2-mercaptopyridines. Part 2. An EPR and spin-trapping
      investigation using 2-methyl-2-nitrosopropane and aci-nitromethane as spin traps
      in aqueous solutions.
AB  - Compounds possessing a pyridine-2-thione moiety show antimicrobial, antifungal
      and anticancer activities. Some of them are also photochemically active and upon
      UV irradiation generate free radicals. In this work, employing EPR and the spin
      traps 2-methyl-2-nitrosopropane (MNP) and aci-nitromethane (NM), we investigated
      the photochemistry in aqueous solutions of N-hydroxypyridine-2-thione (used here
      as a sodium salt, 2-S-PyrNONa), and pyridine-2-thione (2-S-PryH), as well as
      photochemistry of the respective disulfides, 2,2'-dithiobis(pyridine N-oxide) [(2
      S-PyrN-->O)2] and 2,2'-dithiodipyridine [(2-S-Pyr)2]. We found that UV
      irradiation of 2-S-PyrNONa and of 2-S-PyrH in the presence of MNP and NM
      generates EPR signals of reduced spin traps in addition to signals of MNP and NM
      adducts with aryl-thiyl radicals, 2-.S-PyrN-->O and 2-.S-Pyr. The identification
      of the aromatic thiyl radicals was based on comparison of EPR spectra of spin
      adducts generated by irradiation of 2-S-PyrNONa and 2-S-PyrH with those produced
      by UV photolysis of the respective disulfides (2-S-PyrN-->O)2 and (2-S-Pyr)2. It
      is concluded that pyridine-2-thione and N-hydroxypyridine-2-thione possess a
      photoreducing capacity and generate aromatic thiyl radicals upon UV activation.
      This property may be relevant to biological action of agents containing the
      pyridine-2-thione moiety.

PMID- 7800717
TI  - An 125I-labeled N6-substituted azido analog of NAD+ for the photoaffinity
      labeling of NAD(+)-linked enzymes.
AB  - 125I-N6-(N-[6-N-(5-iodo-4-azidosalicyl)-aminohexyl]- aminocarbamoylmethyl)
      nicotinamide adenine dinucleotide (125I-N6-I-ASA-AH-NAD+) was synthesized by
      coupling N6-([6-aminohexyl]-carbamoylmethyl)-NAD+ with 4-azidosalicylic acid N
      hydroxysuccinimide ester followed by radioiodination. The utility of 125I-N6-I
      ASA-AH-NAD+ as an effective site-directed photoprobe was demonstrated by the
      photolabeling of both glutamate dehydrogenase and 15-hydroxyprostaglandin
      dehydrogenase. Both enzymes can be saturated with labeled probe with apparent
      dissociation constants comparable to those reported for NAD+. Photoincorporation
      of the probe into both enzymes was found to be protected specifically by NAD+.
      These results indicate that 125I-N6-I-ASA-AH-NAD+ can be a specific photoprobe
      for NAD(+)-linked enzymes.

PMID- 7800718
TI  - 8-methoxypsoralen increases daytime plasma melatonin levels in humans through
      inhibition of metabolism.
AB  - It is well established that in healthy humans oral intake of 5- or 8
      methoxypsoralen (5- and 8-MOP) is followed by a significant increase in plasma
      melatonin concentrations. The effect of psoralen on rat melatonin has been
      studied in vitro and in vivo and a stimulation of release or secretion from the
      pineal gland has been suggested. In this study we examined the time-related
      changes in plasma concentrations of 8-MOP, melatonin and 6-sulfatoxymelatonin in
      15 patients admitted for routine psoralen plus UVA therapy. On the first day of
      treatment blood samples were collected before, and 30, 60, 66 and 90 min after
      intake of 8-MOP (0.6 mg/kg). Although the rate of 8-MOP absorption varied
      greatly, a significant increase (P = 0.0002) in melatonin levels was found 60 min
      after 8-MOP intake. During UVA exposure a strongly correlated decrease in mean
      melatonin and mean 8-MOP concentrations was found, indicating an effect of UVA
      radiation, either direct or 8-MOP mediated, on circulating melatonin levels.
      Plasma 6-sulfatoxymelatonin concentrations decreased significantly between all
      time points, suggesting inhibition of melatonin metabolism.

PMID- 7800719
TI  - Does low-intensity He-Ne laser radiation produce a photobiological growth
      response in Escherichia coli?
AB  - A photobiological study was carried out on the bacterium Escherichia coli in
      order to determine whether stimulation of growth occurred after irradiation of an
      inoculum with coherent red light. No enhancement or inhibition of growth was
      observed for cultures of the bacterium following irradiation of inocula with a
      Helium-neon laser (continuous wave, lambda = 632.8 nm) at irradiances of 7.7 x
      10(15) and 1.8 x 10(16) photons cm-2 s-1 using fluences of 4.5 x 10(-1) and 4.5 J
      cm-2 at each irradiance. Bacterial growth in irradiated and control cultures was
      monitored during a growth period of ca 2 h using a viable count technique after
      inocula in the early exponential phase had been diluted with fresh growth medium.
      These results do not provide support for the work of Karu et al. (1983, Nuov.
      Cim. 2D, 1138-1144), and Tiphlova and Karu (1988, Photochem. Photobiol. 48, 467
      471), which appear to show substantial enhancement of E. coli growth under these
      conditions.

PMID- 7800720
TI  - A comparison of direct and liposomal antibody conjugates of sulfonated aluminum
      phthalocyanines for selective photoimmunotherapy of human bladder carcinoma.
AB  - There is a need to improve the selectivity of photodynamic therapy and for better
      targeting of tumor cells within specific tumor compartments. Selective in vitro
      phototoxicity of a human bladder carcinoma cell line 647V has been achieved by
      targeting sulfonated aluminum phthalocyanines (AlSPc) with monoclonal antibodies.
      Aluminum tetra-3 sulfonyl chloride phthalocyanine (PC) or rhodamine sulfonyl
      chloride were directly coupled to antibodies by a sulfonamide linkage and AlSPc
      or carboxyfluorescein were encapsulated in liposomes of the small unilamellar
      vesicle type (SUV) bearing antibody. Antibody E7 (IgM subclass), which recognized
      an antigenic determinant expressed on 647V but was absent on T24 a control human
      bladder carcinoma cell line, and a control IgM antibody were used. The effects of
      the two types of conjugate were compared. Immunofluorescence studies on living
      cells demonstrated specific cell surface localization of conjugates at 4 degrees
      C and internalization at 37 degrees C. Phototoxicity was measured by 3-(4,5
      dimethylthiazol-2-5-diphenyltetrazolium) bromide assay after exposing AlSPc
      sensitized cells to red light. Significant AlSPc dose-dependent phototoxicity of
      the order 4 degrees C < 4 degrees C plus 37 degrees C < 37 degrees C was observed
      with E7-SUV and E7-PC in the range 1-8 microM AlSPc. At equimolar AlSPc doses
      absolute toxicity was similar for the two conjugate types, but at equimolar
      antibody doses, the liposomal conjugate was more effective by up to 13-fold.
      Addition of urine during illumination decreased toxicity, which was attributed to
      the presence of protective elements. The results suggest that photosensitizers
      such as AlSPc could be used for antibody-directed therapy and in particular for
      selectively damaging tumor cells of the epithelial cell compartment in bladder
      carcinoma by intrabladder administration. The therapeutic ratio, which takes into
      account both specific and nonspecific toxicity, was greater for the liposome
      conjugate than for the direct conjugate indicating their greater suitability for
      in vivo instillation.

PMID- 7800721
TI  - Enhanced macrophage cytotoxicity against tumor cells treated with photodynamic
      therapy.
AB  - In vitro treatment of human lung adenocarcinoma cells A549 with photofrin-based
      photodynamic therapy (PDT) resulted in the potentiation of macrophage-mediated
      killing of these cells assayed either by measuring 3H-thymidine release from the
      prelabeled target cells, or by determining the survival of A549 cells based on
      colony formation. The effector cells in these experiments were human
      promyelocytic leukemia cells HL60 induced to differentiate into macrophages. Very
      similar results were obtained with the murine squamous carcinoma SCCVII cells
      treated with PDT and subsequently admixed with mouse peritoneal macrophages. This
      effect increased with PDT dose and reached its maximum (i.e. complete or nearly
      complete release of the radioactive label) with the photodynamic treatment that
      was lethal to 40-50% of cells. In contrast, the PDT treatment of normal mouse
      kidney cells resulted in only a very limited enhancement of their cytolysis by
      mouse peritoneal macrophages. The exposure of A549 cells to X-ray irradiation had
      not affected the macrophage-mediated killing of these cells. The PDT survival
      curves of A549 cells cultured either alone or with the effector cells showed that
      the presence of macrophages even at very low effector: target cells ratios
      enhanced the PDT response of tumor cells. The enhancement ratio of 3.6 (at S =
      0.01) was achieved with the effector: target cell ratio 2.5:1, which was the
      highest ratio tested with this assay. It is suggested that macrophages may
      recognize potentially repairable damage induced by PDT in tumor cells (presumably
      lipid fragments exposed in damaged cellular membranes), which helps them to
      identify the affected cells as their targets.

PMID- 7800722
TI  - Evidence for the existence of membrane-associated phytochrome in the cell.
AB  - Comparative fluorescence and photochemical studies of phytochrome in etiolated
      seedlings of maize and in soluble and membrane-containing fractions isolated from
      them were carried out. The membrane fractions prepared in the absence of Mg2+
      from etiolated coleoptiles contained 13% of total photoreversible phytochrome,
      which was readily solubilized by mild detergents. Its molecular size was
      indistinguishable from soluble phytochrome and equal to nondegraded maize
      phytochrome. Low-temperature fluorescence studies with intact tissue found that
      the position of the emission maximum at 85 K (lambda max) and the extent of the
      phototransformation of the red-absorbing form (Pr) into the first stable
      photoproduct, lumi-R, at 85 K (gamma 1), varied in different parts of etiolated
      seedlings: lambda max and gamma 1 reached their maximum values in the tips of
      coleoptiles and roots, 686 nm and 0.30-0.40, whereas the lowest values, 682 nm
      and ca 0.05, were observed in the root base. These parameters correlated well
      with those obtained for the pigment in the soluble and membrane-containing
      fractions: 684 and 680 nm, and 0.33 and 0.06, respectively. The extent of the Pr
      phototransformation into the far red-absorbing form (Pfr) (gamma 2) did not
      differ much: values of 0.80-0.85 and 0.70-0.75 correlated with the high and low
      values of gamma 1. These variations of the parameters were interpreted in
      agreement with our previous observations in terms of two phytochrome A species
      whose relative concentrations vary depending on the experimental conditions--the
      longer wavelength bulk light-labile species with high gamma 1 (Pr'), and the
      shorter wavelength minor light-stable species with low gamma 1 (Pr").(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7800723
TI  - Soft-diet feeding during development enhances later learning abilities in female
      rats.
AB  - We investigated whether a decrease in masticatory work affected not only jaw bone
      growth but also radial eight-arm maze learning, and whether there was a sexual
      difference in this effect, if any. Male and female rats, weaned at 3 weeks of
      age, were fed either pelleted or powdered chow until 16 weeks of age and learning
      experiments were conducted at 10-13 weeks of age. Almost all of the five
      dimensions of the jaw bones were greater in rats fed pelleted chow than in rats
      fed powdered chow in both sexes. The number of correct choices in the last five
      trials was significantly greater in female, but not in male, rats fed powdered
      chow, and the number of trials to attain at least seven correct choices in the
      first eight choices in five consecutive trials was greater in female rats fed
      pelleted chow than in female rats fed powdered chow and in male rats fed either
      powdered or pelleted chow. These results suggest that 1) a decrease in
      masticatory work due to soft-diet feeding during development enhances later
      learning ability preferentially in female rats, and 2) the reported sexual
      inferiority of female rats in learning and memory functions is due to hard-diet
      feeding as the standard laboratory condition.

PMID- 7800724
TI  - Naloxone stimulates oxygen consumption but not ventilation in hypothyroid
      hamsters.
AB  - Male golden Syrian hamsters made hypothyroid by 5 wk of propylthiouracil (PTU)
      treatment and control hamsters given tap water were studied. Both groups of nine
      animals demonstrated increased oxygen consumption after SC naloxone
      administration relative to saline treatment. Naloxone stimulated ventilation and
      ventilation in response to hypoxic (10% O2) and hyperoxic, hypercapnic (7% CO2 in
      oxygen) challenges in control hamsters. Relative to their responses to saline,
      PTU-treated hamsters exhibited no stimulation of ventilation nor of ventilation
      in response to the gas challenges after naloxone treatment. These results suggest
      that (a) the stimulation of oxygen consumption by naloxone does not directly
      increase ventilation; and (b) thyroid hormone status in the hamster affects
      opioid modulation of ventilation.

PMID- 7800725
TI  - Acute exercise and cardiovascular responses to stress in rats.
AB  - The purpose of this study was to determine if acute exercise (EX) reduces the
      cardiovascular response to air jet stress (AJS) in rats. Male Sprague-Dawley rats
      (n = 11) were instrumented with Doppler flow probes and a carotid arterial
      catheter to determine mean arterial pressure (MAP), heart rate (HR), mesenteric
      blood flow (MesBF), and iliac blood flow (IliBF). Rats participated in two trials
      (random order, separated by 48 h): 1) nonexercise (NONEX; 90-min rest on
      treadmill, 20-min restraint, and 20-min AJS), and 2) exercise (EX; 60-min rest on
      treadmill, 30-min EX at 20 m/min, 20-min restraint, and 20-min AJS). Increases in
      MAP (EX = 11 +/- 2%; NONEX = 21 +/- 2%) and HR (EX = 22 +/- 4%; NONEX = 33 +/-
      3%) in response to the AJS protocol (restraint+AJS) were significantly less after
      EX compared to NONEX. Furthermore, decreases in MesBF (EX = -12 +/- 7%; NONEX = 
      29 +/- 8%) and increases in IliBF (EX = 29 +/- 16%; NONEX = 56 +/- 9%) produced
      by combined restraint+AJS were significantly less after exercise. Interestingly,
      the effects of exercise were most evident in response to the mild restraint
      required for AJS. The results suggest that acute EX reduces the cardiovascular
      responses to an AJS protocol (restraint+AJS) in normotensive rats.

PMID- 7800727
TI  - Amiloride reduces the aversiveness of acids in preference tests.
AB  - Experiments were conducted to determine the relative contribution of amiloride
      sensitive pathways to the aversiveness of acid stimuli in preference tests
      performed on male Golden Syrian hamsters. In Experiment 1 hamsters were given a
      choice between water and test solutions in two-bottle preference tests lasting 4
      days. The results showed that although citric acid at pH 3.0-5.0 was not
      aversive, at pH 1.4 or 2.0 citric acid was avoided by all animals, as indicated
      by both consummatory behavior and licking activity. Experiment 2 was conducted to
      determine whether amiloride could reduce the aversiveness of citric acid in
      preference tests. Citric acid at pH 2.4, an aversive solution, and citric acid at
      pH 3.8, which was not aversive, were tested either alone or in the presence of
      amiloride. Amiloride (30-300 microM), which when presented alone was neither
      preferred nor avoided, significantly reduced the aversiveness of citric acid at
      pH 2.4, similar to its effect on NaCl aversiveness. However, amiloride had no
      effect on intake of citric acid at pH 3.8, nor upon preference for saccharin.
      These results support those found in isolated hamster taste cells and from in
      situ taste bud recordings, which suggested that amiloride-sensitive pathways
      contribute to the transduction of acidic stimuli.

PMID- 7800726
TI  - Age-dependent effects of CCK and devazepide in male and female rats.
AB  - Peripheral administration of the brain/gut peptide cholecystokinin (CCK) has been
      demonstrated to inhibit food intake in a variety of species, and administration
      of the specific type A CCK receptor antagonist devazepide increases food intake
      in a variety of experimental paradigms. The potency of CCK to inhibit intake
      depends upon a variety of factors, but CCK is generally less potent under
      conditions of elevated food intake. At different developmental stages, rats'
      intake requirements differ as growth rates change. To determine whether CCK plays
      a variable role in the control of intake in rats of different ages, we examined
      the feeding-inhibitory effect of various doses of CCK and the feeding-enhancing
      potential of various doses of devazepide on glucose consumption (0.5 kcal/ml) in
      male and female rats at 45-70 and 110-130 days of age. CCK was more potent in
      older male and female rats than in younger rats, and inhibited intake in a dose
      related fashion. In younger rats, the efficacy of CCK was attenuated and the
      inhibition was not dose related. Administration of devazepide had no effect on
      intake in younger rats of either sex, but significantly increased glucose
      consumption in the older rats. These data suggest that during a period of rapid
      growth and high levels of food intake relative to body weight, adolescent rats
      are relatively insensitive to exogenous CCK and endogenous CCK does not appear to
      play a significant role in controlling their intake.

PMID- 7800728
TI  - No effect of oral or sample temperature on sensory assessment of fat content.
AB  - This work examined the possible influences of oral and sample temperature on the
      perception of fat content of a model food system. Melting or related phenomena
      may contribute to the greater sensation of fat content and the highly acceptable
      textural characteristics associated with certain fats. Thirty-one adults assessed
      the fat content of 0%, 12%, 24%, 36%, and 48% oil-in-water emulsions prepared
      with a commercial cocoa butter substitute having a melting range of 17-41 degrees
      C. Samples were evaluated at combinations of sample and mouth temperatures of 20
      and 36 degrees C, with oral temperatures manipulated by repeated cold- and warm
      water rinses prior to assessments. There were no significant differences amongst
      these treatments on perceived fat content of the samples, nor were subject
      characteristics of age or body composition related to judgments of fat content in
      these stimuli. Although previous studies had shown that degree of fat saturation
      is associated with enhanced perception of fat content (11), that does not appear
      to be related to the degree or occurrence of melting in the mouth over the ranges
      studies here.

PMID- 7800729
TI  - Development of righting when falling from a bipedal standing posture: evidence
      for the dissociation of dynamic and static righting reflexes in rats.
AB  - Righting to prone when placed supine on the ground by rats is present at birth,
      albeit in incomplete form. In contrast, righting in the air when falling from the
      supine position does not begin to emerge until the end of the first week and is
      not complete until the end of the third week postnatally. On the ground, the
      animals have sensory information from proprioceptive-tactile sources, as well as
      vestibular; in the air, they have only vestibular. Thus, it is possible that the
      difference between contact righting and air righting is a reflection of the
      relative difference in the maturation of tactile vs. vestibular mechanisms. In
      this study, pups were tested by pushing them backwards from a bipedal standing
      position. Such a context provided proprioceptive-tactile information during the
      fall. The results showed that the developmental onset and maturation of righting
      from the bipedal position resembled that of air righting rather than contact
      righting. This suggests that the difference between air righting and contact
      righting is not due to differences in sensory inputs, but to differential
      maturation of neural mechanisms for acceleratory (i.e., falling) vs. stationary
      (i.e., lying on the ground) forms of righting. That is, the appropriate neural
      systems are organized for the type of righting, not for the sensory systems used.
      Even so, some evidence is provided suggesting a developmental dissociation
      between righting from falling with vestibular information only, and with
      proprioceptive-tactile information in addition. Therefore, righting systems
      appear to need two dimensions of classification--one based on sensory systems
      involved, and the other in terms of the context of righting (i.e., falling vs.
      stationary).

PMID- 7800730
TI  - Combined effects of Depo-Provera and Fadrozole on the sexual behavior of intact
      male cynomolgus monkeys (Macaca fascicularis).
AB  - Our previous studies showed that treating castrated, testosterone-treated male
      cynomolgus monkeys with Depo-Provera (medroxyprogesterone acetate, MPA) decreased
      ejaculatory performance and also measures of male sexual motivation by about 40%.
      Similarly, treating castrated, testosterone-treated males with the nonsteroidal
      aromatase inhibitor, Fadrozole, decreased ejaculatory performance and male sexual
      motivation again by about 40%. These behavioral decrements are, of course,
      mediated by totally different mechanisms. We have therefore hypothesized that
      both unchanged T and E2 might be important for the control of sexual behavior in
      this male primate, and the present study examined the consequences of
      administering Fadrozole at a dose of 0.25 mg/kg/day to intact male cynomolgus
      monkeys being treated with 40 mg/week MPA. Intact males were each tested with an
      ovariectomized, E2-treated female partner (i) before treatment, (ii) during
      treatment with MPA alone, and (iii) during treatment with MPA and either
      Fadrozole or water administered SC by osmotic minipumps. As in previous studies,
      MPA significantly decreased plasma T levels and sexual behavior. But additional
      treatment with Fadrozole resulted in a rapid increase in plasma T levels although
      causing a further decline in sexual behavior. Results supported the view that
      both unchanged T and its aromatized product are important for ejaculatory
      activity and sexual motivation in the primate. Fadrozole's effect on plasma T may
      have been due to the elimination of the negative feedback of E2 on the
      hypothalamic-pituitary-gonadal axis.

PMID- 7800731
TI  - Flight-elicited attack and priming of aggression in nonaggressive hamsters.
AB  - We report a technique for inducing attack in apparently nonaggressive hamsters
      that takes advantage of several behavioral effects: (a) the vigorous flight that
      repeatedly defeated hamsters display in the presence of conspecifics, (b) the
      potent, attack-eliciting properties of such flight, and (c) attack priming (i.e.,
      aggressive arousal from exposure to an initial stimulus animal carries over to
      exposure to a second one). Resident hamsters that had consistently failed to
      attack nonfleeing intruders were found to readily attack intruders that did flee.
      But repeated exposure to the fleeing intruders alone did not induce long-term
      changes in aggressiveness. However, flight-elicited attack did successfully prime
      attack onto nonfleeing intruders presented immediately after the fleeing intruder
      was removed. Repeating such priming transfer trials induced long-term changes in
      the formerly nonaggressive subjects. We conclude that this is an effective
      procedure for inducing aggression that would be preferred when it is important to
      avoid exposing subjects to aversive stimuli. The changes in behavior that we
      observed seem to reflect heightened motivational levels.

PMID- 7800732
TI  - Physical activity does not account for the physiological response to forced swim
      testing.
AB  - Two experiments were conducted to examine physiological variables associated with
      the immobility response in the forced swim test. The first study compared the
      effects of water immersion, treadmill running, and foot shock, and showed that
      the time-related pattern of reactions to these three conditions, especially those
      involving lactate, glucose, anion gap (a measure of metabolic acidosis), and
      carbon dioxide differed significantly. The second study examined the role of food
      deprivation, and showed that this manipulation does not affect the behavior or
      physiological response of rats to testing. These results indicate that the
      physiological changes occurring during the forced swim are not simply due to
      increased physical activity or stress.

PMID- 7800733
TI  - Tonic-clonic convulsions in meadow voles.
AB  - Some meadow voles (Microtus pennsylvanicus) exhibit prolonged tonic-clonic
      convulsions, possibly epileptiform seizures, when handled or exposed to a strange
      environment. These convulsions are often preceded by a period of slow head
      shaking and/or stiff-legged hopping, but never by the explosively wild running
      bouts that characterize convulsions in some mammals. Convulsions occasionally
      occur in meadow voles in response to mild disturbance, as when an individual in
      its home cage is carried from one room to another. In contrast, they can not be
      elicited by some of the auditory or olfactory insults used to induce epileptiform
      seizures in other mammals. Breeding experiments have established the genetic
      basis of the convulsions seen in meadow voles, and of particular interest here is
      the fact that some of the convulsing voles were caught in the wild. This raises
      the interesting possibility that wild voles in natural habitats might be
      susceptible to convulsions when startled.

PMID- 7800734
TI  - Leg position learning in the cockroach nerve cord using an analog technique.
AB  - The ultimate goal of this research is to correlate neural activity with leg
      behavior during learning. Contrary to previous studies of shock avoidance
      learning in the headless cockroach, in which an all-or-none method of recording
      was used, we have adopted a direct analog recording of leg position to measure
      learning in the prothoracic ganglion. This method provides a sensitive and
      continuous record of leg movement that can be correlated with the interactions of
      individual neurons that may be involved in such learning. Of the 10 prothoracic
      legs trained to flex to avoid shock, eight escaped shock by flexion within a
      maximum of 13 min and seven showed savings when retested. Only four of eight
      prothoracic legs trained to extend showed avoidance learning and all four showed
      savings. Electrical stimulation of nerves 3,4,5, and 6 innervating the
      prothoracic leg revealed which nerves were instrumental in the flexion and
      extension responses.

PMID- 7800735
TI  - Olfaction mediates the establishment of selective bonding in goats.
AB  - Nine pregnant goats of the Creole breed were rendered anosmic 3 weeks before
      parturition by irrigating their olfactory mucosa with zinc sulfate, and nine
      additional pregnant goats were left intact. At parturition, interactions between
      all females and their young were observed for 1 h. No differences were found in
      mother-young relationships between intact and anosmic mothers during this time,
      except that kids from anosmic females were slower to suck than controls. After 4
      h of uninterrupted mother-young, mothers underwent three successive 5-min tests
      in a predetermined order to study selective bonding: with their own kid, an alien
      kid of similar coat color and pattern, and an alien kid of dissimilar coat color
      and pattern. Intact goats readily discriminated between kids, and rejected the
      two aliens while accepting their own. By contrast, anosmic mothers showed no
      signs of discrimination and accepted the three types of kids. It is concluded
      that during the first postpartum hours of contact, mother goats memorize
      individual olfactory characteristics of their kid that serve as a basis for
      selective suckling and exclusive bonding. Furthermore, at this early stage,
      visual characteristics of the young do not appear able to compensate for the loss
      of olfactory cues.

PMID- 7800736
TI  - Nutrient-conditioned flavor preference and acceptance in rats: effects of
      deprivation state and nonreinforcement.
AB  - Rats acquire strong preferences for flavors paired with intragastric (IG)
      Polycose infusions. The present study investigated the ingestive responses to
      these flavors when they were no longer reinforced. All rats were first trained to
      associate a CS+ flavor with IG 32% Polycose and a CS- flavor with IG water during
      23 h/day sessions. Experiment 1 examined the effects of deprivation on short-term
      (4 h/day) CS intakes under nonreinforcement conditions. Food deprivation
      selectively enhanced CS+ intake whereas water deprivation increased both CS+ and
      CS- intakes. The results also suggested that extinction training differentially
      affects CS+ preference and acceptance as measured by relative and absolute
      intakes. This was confirmed in a second experiment. The rats' absolute intake of
      the CS+ solution during 4 h/day sessions significantly decreased when it was no
      longer paired with IG Polycose infusions; yet the rats continued to show a strong
      preference for the CS+ over the CS- in both 4 h and 23 h/day tests. Experiment 3
      examined the effects of extensive long-term extinction training on the CS+
      preference. When the alternative was plain water, the CS+ preference extinguished
      over 12 days. Yet the same rats continued to prefer the CS+ to the CS- during 12
      additional extinction days and during 16 extinction days that followed a 1-month
      rest period. The CS+ preference relative to the CS- was blocked only when the CS+
      was paired with food deprivation and the CS- was paired with food repletion.
      These experiments confirm earlier reports of the resistance of Polycose
      conditioned flavor preferences to extinction but also show that flavor acceptance
      is more susceptible to extinction. Flavor acceptance was not completely
      extinguished, however, and remained responsive to deprivation state.

PMID- 7800737
TI  - Central amygdaloid lesions attenuate cardiovascular responses to acute stress in
      rats with borderline hypertension.
AB  - The present study tested the hypothesis that lesions of the central nucleus of
      the amygdala (CeA) would reduce the cardiovascular responses to acute stress in a
      rodent model that is genetically predisposed toward hypertension. Male borderline
      hypertensive rats (BHR) were given bilateral electrolytic lesions directed to
      destroy the CeA or were subjected to a sham procedure. Direct measurements of
      blood pressure and heart rate were recorded during rest, during 10 min of acute
      stress, and for 10 min following stress. Analysis of the data revealed that BHR
      with CeA lesions had a significant attenuation of the stress-induced pressor
      response compared to sham-operated subjects. Behavioral measures taken in an open
      field chamber before and after lesions revealed no differences in numbers of
      squares crossed or rearings. These results suggest that the CeA is an important
      neural structure in mediating cardiovascular responses to acute stress in a model
      susceptible to environmentally induced hypertension.

PMID- 7800738
TI  - Cerebellar and mesencephalic influence on bulbar penicillin-G epileptogenesis in
      rats.
AB  - The influence of the cerebellum and mesencephalon on epileptic bulbar discharge
      induced by topical application of penicillin-G on the floor of the IVth ventricle
      was analyzed in rats. Bulbar multiunit activity was recorded at different depths.
      The animals were divided into two main groups: totally cerebellectomized rats
      (Group I) and lobus anterior cerebellectomized rats (Group II). Each main group
      was further subdivided into two subgroups: animals with intact mesencephalon and
      animals with transected mesencephalon. In Group I: the total cerebellectomy, in
      intact mesencephalic rats (first subgroup) induced a sudden disappearance of
      bulbar epileptic discharge. The mid-collicular transection (second subgroup)
      produced the immediate disappearance of bulbar paroxysms and the total
      cerebellectomy, subsequently performed, further decreased the spontaneous firing
      rate. In Group II: (first subgroup) the lobus anterior ablation in rats with
      intact mesencephalon, significantly enhanced the paroxysmal discharge. In the
      second subgroup, where the midcollicular transection had provoked the
      disappearance of bulbar paroxysms, the lobus anterior ablation induced the
      immediate reappearance of the paroxysmal activity. The penicillin-G epileptogenic
      activity showed a different intensity at different depths in the bulb with a
      maximum intensity at the level of the vestibular nuclei. In conclusion, the
      present study shows that both the mesencephalon and the cerebellum have a
      facilitating influence on bulbar epileptic discharge induced by the topical
      application of the GABA antagonist. However, not all the cerebellum has a
      facilitating effect, because the anterior lobus was found to have an inhibitory
      influence on bulbar discharge.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7800739
TI  - Effects of smoking on memory for prose passages.
AB  - The present study examined the effects of smoking on memory for prose passages.
      Habitual male smokers were matched on verbal ability, impulsivity level, and
      habitual smoking level and were instructed to smoke either a 0.1 mg (control), a
      0.7 mg, or a 1.5 mg nicotine cigarette in a controlled fashion. Immediate recall
      after reading expository passages was obtained. The results indicated that the
      subjects who smoked the 0.7 mg nicotine cigarette recalled a greater proportion
      of the idea units than the control group, with no difference between the 1.5 mg
      group and the control. In addition, blood pressure and heart rate significantly
      increased in all groups immediately after smoking, with heart rate increases
      greater in the 0.7 mg and 1.5 mg groups than the control. Interpretive hypotheses
      for the results include arousal theory, with optimal arousal levels being
      obtained in the 0.7 mg nicotine group for the prose recall task, and nicotine
      specific effects, including nicotine's influence on the cholinergic system.

PMID- 7800740
TI  - Retronasal or internasal olfaction can mediate odor-guided behaviors in newborn
      mice.
AB  - Studies of olfactory deprivation have most frequently used unilateral naris
      occlusion to effect deprivation. Recent psychophysical evidence suggests that
      adult rodents with either acute or chronic naris occlusion show little decrement
      in olfactory ability. In this study the effect of naris occlusion coupled with
      ipsilateral or contralateral olfactory bulb deafferentation on odor-guided
      behaviors was tested in neonatal mice. Animals that received bilateral bulbectomy
      or control manipulation were also included. In Experiment 1, olfactory lesions
      were produced by bulb aspiration on the second day after birth (P2). Daily weight
      gain, a reliable measure of suckling success, was recorded until P21. In
      Experiment 2, olfactory lesions consisted of bulb transection on P2. Daily
      weights were recorded until subjects were P10. Animals with bilateral bulbectomy
      had the highest mortality rate and slowest growth rate. Both naris occlusion
      groups grew more slowly than controls but were not significantly different at P5
      or P10. They diverged, thereafter, such that at P20 the group with naris
      occlusion ipsilateral to bulbectomy was similar to controls, while the
      contralateral group was similar to the bilateral bulbectomy group. In Experiment
      2, the weights of the naris occlusion groups diverged by the day after surgery,
      with the contralateral group suffering the most arrested growth. Behavioral tests
      were combined from the two experiments for analysis. Subjects were tested at P5
      for their ability to find the nipple, at P8 for their ability to find the nest,
      and at P10 for unwashed vs. washed nipple preferences. Only the contralateral
      group had a significantly depressed ability to find the nipple, while all lesions
      groups had a significant but similar decline in nest-finding ability.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7800741
TI  - Effect of photoperiod on mitochondrial GDP binding and adenylate cyclase activity
      in brown adipose tissue of Djungarian hamsters.
AB  - Experiments were designed to investigate the involvement of brown adipose tissue
      (BAT) thermogenesis in the weight loss exhibited by Djungarian hamsters (Phodopus
      sungorus campbelli) in response to a short photoperiod. Significant decreases in
      body weight preceded reductions in food intake, suggesting a photoperiod-induced
      change in energy expenditure. Sixteen weeks exposure to short photoperiod
      resulted in large decreases in body weight and interscapular BAT mass that were
      accompanied by an increase in the thermogenic activity of BAT (estimated by
      mitochondrial GDP binding). However, exposure to short photoperiod for 8 weeks,
      that induced smaller but significant reductions in body weight, was without
      effect on the BAT parameters measured. This suggests that increased BAT
      thermogenesis is unlikely to initiate, or contribute to, the early stages of
      photoperiod-induced weight loss. In addition, short photoperiod failed to induce
      any change in the specific activity or sensitivity of adenylate cyclase in BAT
      membranes, in contrast to the downregulation of catecholamine-stimulated cAMP
      production observed in BAT following cold exposure.

PMID- 7800742
TI  - Differences in taste responses to Polycose and common sugars in the rat as
      revealed by behavioral and electrophysiological studies.
AB  - Behavioral and electrophysiological experiments were performed to examine the
      suggestion that rats have two types of carbohydrate taste receptors, one for
      polysaccharides (e.g., Polycose) and one for common sugars (e.g., sucrose).
      Qualitative difference between the tastes of Polycose and sugars including
      sucrose, maltose, glucose, and fructose was surveyed by means of a conditioned
      taste aversion paradigm in which the number of licks for 20 s to each taste
      stimulus was measured. Aversive conditioning to Polycose did not generalize to
      sugars, while aversive conditioning to sucrose generalized to other sugars, but
      not to Polycose. In the electrophysiological study, taste responses of the whole
      chorda tympani were recorded. A proteolytic enzyme, pronase E, suppressed nerve
      responses to both Polycose and sugars to less than 50%. A novel anti-sweet
      peptide, gurmarin, strongly suppressed responses to sugars, but had essentially
      no effect on Polycose responses. On the other hand, KHCO3 enhanced responses to
      sugars to about 300%, but had little effect on Polycose responses. These results
      have confirmed the notion that rats can differentiate the tastes between Polycose
      and common sugars and that rats have two types of carbohydrate receptors.

PMID- 7800743
TI  - Stress-induced hyperthermia in mice: hormonal correlates.
AB  - In the stress-induced hyperthermia (SIH) paradigm in group-housed male mice, the
      rectal temperature of last measured mice is approximately 1.5 degrees C higher
      than the first measured one when the temperature of each mouse is measured
      sequentially with an interval of 1 min. In the present study it is demonstrated
      that SIH is accompanied by increases in plasma ACTH, corticosterone, and glucose
      levels that return to baseline more or less parallel to the temperature. The
      simultaneous increases in temperature and plasma stress hormones strongly support
      the use of the SIH paradigm in mice as an animal model to study putative anti
      stress or anxiolytic properties of drugs.

PMID- 7800744
TI  - Cohabitation alters vasopressin innervation and paternal behavior in prairie
      voles (Microtus ochrogaster).
AB  - The density of vasopressin-immunoreactive (AVP-ir) fibers in the lateral septum
      and lateral habenular nucleus is lower in prairie vole fathers--which display
      paternal behavior under natural conditions-than in sexually naive males. To see
      if these changes occur before or after the birth of pups, and whether they are
      related to changes in paternal behavior, we tested paternal responsiveness and
      measured AVP-ir fiber density in the lateral septum, lateral habenular nucleus,
      medial preoptic area, and paraventricular nucleus of the thalamus of sexually
      naive males and females (0P) and breeding pairs that were sacrificed shortly
      after mating (3P); during early (13P); or late gestation (21P); or after the
      birth of pups (6PP). Paternal responsiveness was increased in 3P males and
      reached a plateau in 13P males. AVP-ir fiber density did not change in the medial
      preoptic area and the paraventricular nucleus of the thalamus. The fiber density
      in the lateral septum and lateral habenular nucleus was affected differently in
      males and females. Among males, 3P animals had the lowest fiber density, while
      13P and 6PP animals had an intermediate, and 0P and 21P animals the highest fiber
      density, whereas among females, no differences in fiber density were found. A
      second experiment showed that the decrease in fiber density in 3P males could be
      induced by cohabitation with an unfamiliar female but not by an unfamiliar male
      nor by relocation to a novel cage. The changes in AVP-ir fiber density shortly
      after mating suggest that these fibers may be involved in paternal responsiveness
      as well as in various other social behaviors that change after mating.

PMID- 7800745
TI  - Effects of fimbria-fornix lesions on avoidance tasks with temporal elements in
      rats.
AB  - Sidman schedule active avoidance, passive avoidance, and multiple avoidance
      (continuous alternation of active and passive avoidance) tasks were given to
      fimbria-fornix (FF)-lesioned (n = 10) and control (n = 10) rats to assess the
      effects of fimbria-fornix lesions on unsignaled avoidance learning with temporal
      cognition requirement. Active avoidance required subjects to make running
      responses, and passive avoidance required them to stop running and remain
      immobile on a running wheel. The tasks could be achieved purely by temporal cues,
      and no spatial elements were involved. Animals in the FF group performed the
      active, passive, and multiple avoidance tasks as well as control animals, showing
      no deficits by lesions in either the number of running responses nor the number
      of shocks received, although animals in the FF group displayed a greater negative
      transfer in passive avoidance when they received the active training before the
      passive training. The results indicate that fimbria-fornix lesions do not impair
      avoidance tasks when the tasks do not require spatial information, even if
      temporal information and/or inhibition are necessary to perform the tasks.

PMID- 7800746
TI  - Accuracy and reliability of total body electrical conductivity (TOBEC) for
      determining body composition of rats in experimental studies.
AB  - Total body electrical conductivity (TOBEC) has been promoted as a noninvasive
      method to estimate body composition in small mammals. Validation of this method
      has primarily been under normative conditions and has generally been inadequate.
      This article reports on the reliability and accuracy of TOBEC methodology to
      assess gradual, physiologically induced changes in body composition in rats under
      different experimental conditions. Reliability of the index of electrical
      conductivity (EM number) was assessed by analyzing components of variance.
      Accuracy was assessed by comparing EM number to actual lean body mass (LBM, from
      carcass analysis), across different experimental conditions, within a particular
      experimental condition, and over time for a given set of animals. Reliable
      measurements were obtained by strictly adhering to a standard protocol. TOBEC was
      inaccurate across experimental conditions, within experimental conditions, and
      within a single experimental condition during the course of an experiment. This
      inaccuracy apparently stemmed from the lack of a direct relationship between EM
      number and LBM; EM number was more strongly correlated with body weight than with
      LBM. At the present time, TOBEC cannot be used in place of carcass analysis to
      accurately predict the body composition of rats during or following the
      administration of a variety of experimental conditions.

PMID- 7800747
TI  - Dissociated paradoxical sleep deprivation effects on inhibitory avoidance and
      conditioned fear.
AB  - Rats were submitted to paradoxical sleep deprivation (PSD) for 24, 72, or 96 h
      and were trained on a double aversively motivated task, encompassing a step
      through inhibitory avoidance and a classical conditioning of fear to a brief tone
      serving as conditional stimulus. Retention test of the inhibitory avoidance was
      performed at the same apparatus of training (without tone presentation).
      Retention of conditioned fear was assessed in an open field apparatus, where the
      freezing reaction to the tone was measured. PSD for 24 and 72 h preceding the
      training session had no effect on either task. However, PSD during the 96 h
      preceding the training session impaired acquisition of inhibitory avoidance, but
      had no effect on classically conditioned fear. It is concluded that PSD had
      differential effects on the two tasks, both aversively motivated and trained at
      the same time and conditions.

PMID- 7800748
TI  - A high-precision ultrasonic system for vertical movement counts in rats.
AB  - A microcomputer-aided ultrasonic system was used to measure vertical displacement
      of rats in response to drug injection. The system utilizes an inexpensive PC/AT
      microcomputer for data collection and can distinguish between number of vertical
      movements of small (i.e., greater than 5 mm, but less than 15 mm), and large
      (i.e., greater than 15 mm) displacements. In addition, rest time denotes the time
      elapsed for the vertical motion of less than 5-mm displacements. As little as
      0.32 mg/kg of d-amphetamine increased the average amount of both small and large
      activity (i.e., number of movements), but decreased the average amount of rest
      time in rats. On the contrary, as little as 2.5 mg/kg of chlorpromazine decreased
      the average amount of both small and large activity, but increased the rest time
      in rats. When the animal activity was measured with an infrared light system, the
      activity responses to drugs were not detectable. Thus, it appears that the
      ultrasonic method provides a high-precision system for measuring animal
      behaviors.

PMID- 7800749
TI  - Radial arm maze behavior in mice when a return to the home cage serves as the
      reinforcer.
AB  - Male ddY mice were housed in a cage with an eight arm radial maze apparatus for 6
      h a day. A water bottle was placed at the central platform. The end of each arm
      ran to the home cage through a guillotine door (G). Food was placed at the home
      cage. During the housing in the apparatus, one G was raised and the remaining
      seven G were lowered. The raised G was changed every 45 min in random order. Mice
      housed in this apparatus learned efficient strategy to return the home cage by
      trial and error. When they chose the arm in which the G was lowered on their way
      to the home cage from the platform, they returned to the platform, then chose a
      different arm until they were able to enter the home cage. The mice housed in
      this apparatus mastered the radial maze task on the 7th day. When scopolamine
      (SCO) was injected, SCO butylbromide had no effect on performance, but SCO
      hydrobromide (0.2 and 0.4 mg/kg) impaired working memory, dose dependently. These
      results show that the apparatus is useful for ease in estimating working memory
      in mice without the use of severe food or water deprivation.

PMID- 7800750
TI  - Design and performance of an accurate demand feeder for the study of feeding
      behaviour in sea bass, Dicentrarchus labrax L.
AB  - A new demand feeder was designed for the automatic and accurate feeding of fish.
      The feeding device is microcomputer controlled and permits the continuous
      recording of feeding behaviour. The electromechanical feeder consists of a
      sliding door powered by a solenoid which provides only one weighed pellet when
      activated by the fish. Some preliminary results on feeding behaviour in sea bass
      are presented to test the efficiency of the feeder.

PMID- 7800751
TI  - A further analysis of physiological changes in rats in the forced swim test.
AB  - Rats were tested in the forced swim test in 35 or 20 cm of water or in an open
      field to evaluate the effects of different intensities of stress on blood gases,
      electrolytes, and metabolic indices, compared to nontested controls. Animals
      tested in the open field did not differ from controls on any measure. Immersion
      in deep water resulted in a greater mixed metabolic and respiratory acidemia (low
      pH, low bicarbonate, high pCO2), higher glucose and higher lactate levels than
      immersion in shallow water which in turn resulted in greater metabolic acidemia
      (low pH, low bicarbonate), and higher glucose and lactate levels than occurred in
      open field or control animals. In contrast to immersion in deep water, immersion
      in shallow water resulted in an initial hypocapnia followed by a hypercapnia.
      Immersion in deep water also resulted in higher potassium levels, lower
      bicarbonate and total carbon dioxide levels, and a higher anion gap than
      immersion in shallow water, testing in the open field, or in controls. In a
      second study, lactate infusion resulted in a metabolic alkalemia (increased pH
      and bicarbonate levels) and an increase in total carbon dioxide levels. These
      results indicate that test parameters from forced swim testing (e.g., water
      depth) can significantly affect the rat's physiological response to testing. The
      effects of forced swim testing are not simply due to general stress; and the
      physiological changes seen in conjunction with forced swim testing (e.g.,
      acidemia) are not due to lactate alone.

PMID- 7800752
TI  - Social and reproductive influences on plasma cortisol in female marmoset monkeys.
AB  - Subordinate female common marmosets (Callithrix jacchus) undergo ovulation
      suppression and exhibit low plasma cortisol levels compared to the dominant,
      breeding female. To determine whether this cortisol difference is mediated by the
      differential reproductive consequences of social status, we monitored plasma
      progesterone and cortisol in 32 adult female marmosets while they were housed in
      heterosexual pairs, during the first 3 days of heterosexual group formation, and
      while animals were housed in established social groups. Cortisol levels prior to
      group formation were significantly higher in females exhibiting cyclic ovulatory
      activity than in anovulatory females but were not predictive of social status.
      Subsequently, when animals were housed in established social groups, dominant
      (cyclic) females had significantly higher cortisol levels than did subordinate
      (anovulatory) females. Cortisol levels differed between the pre and postgroup
      formation conditions only in animals that underwent a corresponding onset or
      termination of ovulatory cyclicity. Cortisol differences between dominant and
      subordinate female marmosets therefore appear to be associated with differences
      in reproductive function rather than with social status per se.

PMID- 7800753
TI  - A simple method for the calibration and equalization of whole-body startle
      measurements in the rat.
AB  - A dynamic calibration method for startle amplitude measurement systems for rats
      is described that is based on rotating weights. The calibration is dependent
      exclusively on: the mass of the weights, the eccentricity of the weights with
      respect to the rotation axis, and the rotation velocity in revolutions per
      second, all of which are easily and accurately measurable parameters. Because of
      the variability of the frequency spectrum of whole-body startle reactions, it is
      important to measure the frequency transfer function of startle measuring devices
      and if necessary to correct the transfer function in the preamplifier so that a
      flat transfer function in the relevant frequency range results.

PMID- 7800754
TI  - Reliability of the sensory responder classification to learned flavor cues: a
      test-retest study.
AB  - Previous work from this laboratory has examined the extent to which learned
      associations between the flavor of food and the caloric consequences of food
      ingestion influence daily energy intake in humans. We have consistently
      identified a subset of subjects, called sensory responders, whose intakes were
      strongly guided by flavor cues. Sensory responders were identified on the basis
      of post hoc examination of energy intake patterns. The purpose of this study was
      to confirm the reliability of this classification scheme using a test-retest
      paradigm. Eighteen normal-weight, free-living adults participated in the study.
      Subjects were first fed a high-calorie lunch with distinctive flavors for 5
      consecutive days then a low-calorie lunch with different distinctive flavors for
      an additional 5 days. Following this training, the flavors in the lunches were
      covertly switched. Subjects whose intakes were influenced by the change in the
      flavor cues were classified as sensory responders and those whose intakes were
      not influenced by the switch in the flavor cues were classified as sensory
      nonresponders. Subjects then repeated the protocol. All subjects who were
      classified as sensory responders at the end of the first trial were similarly
      classified at the end of the second trial, indicating that their initial
      responses were reliable.

PMID- 7800755
TI  - Stress-induced modulation of the immune response in the developing rat pup.
AB  - Although substantial evidence has linked stressful events to immune changes in
      adult animals, little is known regarding the impact of stress on immune function
      during ontogeny. In the present study, 8-, 16-, and 20-day old rat pups were
      isolated from their mothers and littermates for 24 h; splenocyte responses to the
      mitogen Con A were assessed 72 h following reunion. A suppression of the mitogen
      response was obtained for 16- and 20-day old pups, but no effect was found in the
      8-day-old animals, possibly due to the small sample size. These data offer a
      viable model from which to study further changes in immune responsiveness during
      ontogeny.

PMID- 7800756
TI  - Contribution of locomotor activity to the generation of the daily rhythm of body
      temperature in golden hamsters.
AB  - The locomotor activity and body temperature of 40 golden hamsters maintained
      under a 14L:10D light:dark cycle were studied by telemetry. Body temperature was
      found to be highly correlated with activity. On average, an increase from 0 to
      200 units of activity was associated with a 0.7 degrees C increase in body
      temperature. However, body temperature during the dark phase of the light:dark
      cycle was 0.3 degrees C higher than during the light phase, irrespective of the
      activity level. These results indicate that, although activity can affect body
      temperature, the increase in activity during the dark phase is not the cause of
      the temperature rhythm. At least 30% of the total daily variation in body
      temperature is independent of variations in the activity level.

PMID- 7800757
TI  - Treatment options for the patient with breast cancer.
AB  - There is no one prescription for the treatment of breast cancer, which is the
      most common malignancy among women in the United States and the second leading
      cause of cancer death. This article presents current guidelines for the treatment
      of patients with breast cancer.

PMID- 7800758
TI  - Obtaining a "reasonably accurate" health history.
AB  - Information obtained in a health history is used to assess the patient's current
      health status, evaluate the disease process, and plan the patient's medical and
      surgical nursing care plan. The health history process reviewed in this article
      entails understanding levels of health history, methods of obtaining a health
      history, and challenging health histories. Three levels of health history are
      reviewed: comprehensive, detail-limited, and challenging. A data collection guide
      to improve accuracy of health histories is included.

PMID- 7800759
TI  - Communicating with the deaf patient.
AB  - Three levels of deafness exist: persons who are born deaf, persons who lost
      hearing after speech was acquired, and persons with sudden deafness. Nurses need
      to find methods to communicate with the patient, and not the family in lieu of
      the patient. Props, audio-visual aids, gestures, and written information should
      be used.

PMID- 7800760
TI  - Extramammary Paget's disease: a case study.
AB  - Extramammary Paget's Disease is a rare lesion of the genital, axillary or thorax
      skin that is a counterpart of Paget's Disease of the breast. It is often
      misdiagnosed as eczema or other skin rashes. The lesion may appear as a red,
      crusted, sharply demarcated area with submucosal thickening. This case study
      describes the surgical repair of a perianal wound in a patient with Paget's
      Disease.

PMID- 7800761
TI  - The new job description--can the heart and soul of nursing be preserved?

PMID- 7800763
TI  - Nine steps to organizing patient teaching.

PMID- 7800762
TI  - Pain management with ketamine: a case study.

PMID- 7800764
TI  - Intercultural communication.

PMID- 7800765
TI  - Sampling: the source of the data.

PMID- 7800766
TI  - Nursing in the spotlight: let's seize the moment.

PMID- 7800767
TI  - President's message: nurses must meet the challenges in this age of technology,
      information, and health care reform.

PMID- 7800768
TI  - General principles of flap reconstruction: goals for aesthetic and functional
      outcome.
AB  - Plastic surgeons are often requested to reconstruct defects following traumatic
      injury or after tumor ablation. These defects most commonly occur in the head and
      neck region and in the extremities. Reconstructions must balance the aesthetic
      and functional goals against morbidity of the donor site. This article provides a
      better understanding of reconstructive flaps through application of general
      principles. Flaps are classified according to type. Characteristics of both the
      donor site and the reconstructive recipient site are then explored. Case examples
      serve to illustrate the general principles enumerated.

PMID- 7800769
TI  - Calculated risks in the treatment of intractably suicidal patients.
AB  - PATIENTS who threaten suicide in all seasons, self-mutilate, and who from time to
      time make serious suicide attempts tax and challenge clinical workers. Every
      hospital has its legend about the exploits of such a patient. When these patients
      die of suicide, a wave of sorrow and guilt follows. Many therapists exclude them
      from their practices; keeping clinical balance in working with them is difficult.
      Intractably suicidal patients require much time and great energy from those
      responsible for their care. They draw forensic attention and excite hospital
      administrators to action. Much of the anxiety they arouse comes from the question
      of whether they should be admitted to the hospital and, once they have come into
      the hospital, from the reciprocal: whether they should go out again. The
      increasingly litigious climate in the United States makes the treatment of such
      persons extremely difficult. The purpose of this paper is to review the
      literature pertinent to the care of such patients, to outline the clinical
      principles necessary for their management and treatment, and to set forth the
      conditions that are necessary to minimize legal exposure in the event of suit in
      the wake of suicide.

PMID- 7800770
TI  - Age differences in the personality characteristics of suicide completers:
      preliminary findings from a psychological autopsy study.

PMID- 7800771
TI  - Sudden infant and child death as a cultural phenomenon: a Tlaxcalan case study.
AB  - THE Sudden Death of infants and young children (SICD) constitutes a recurring
      problem in all societies. In contemporary industrialized societies, many factors
      known to cause these deaths have been clarified and controlled. Yet, as an
      outcome of such things as unrecognized disease, accidents, so-called crib death,
      and parental neglect or abuse, the prevalence of SICD remains relatively stable
      even in contemporary Western societies (Adams et al. 1990; Campbell 1989; Kyle et
      al. 1990). The pathophysiology of these human tragedies has received much
      attention. However, the social, cultural, and psychiatric implications have been
      relatively neglected. In large part this is because in our secular culture these
      deaths are explained naturalistically; namely, as the result of disease,
      biological anomalies, or physiological failures, the meaning of which is not
      attributed to human or other worldly intervention. A result of this is that such
      deaths are usually deprived of a framework of meaning that has spiritual and
      existential connection to everyday affairs. An impersonal, natural way of
      explaining SICD often deprives the mourner of a meaningful cultural rationale
      that can facilitate emotional release and spiritual significance.

PMID- 7800772
TI  - Normal and developmental aspects of masochism: transcultural and clinical
      implications.
AB  - Masochism in all its forms has challenged psychoanalytic theories of development
      a and treatment since Freud (1905, 1919, 1924). It might appear paradoxical to
      present a concept of normal masochism while masochism has been considered to be
      so pathological, but I have proposed this concept (Nakakuki 1982, 1984) as a part
      of normal mental functioning through my experience and study of "traditional"
      Japanese culture, which I believe contains the features of normal masochism. It
      is normal in that it represents Japanese adaptation to their cultural orientation
      and expectations.

PMID- 7800773
TI  - Family images of hospitalized adolescents: the failure to generate shared
      understandings.
AB  - Family factors have been implicated clinically in the nonpsychotic
      psychopathology of adolescents (Berkowitz et al. 1974; Feldman and Guttman 1984;
      Gunderson et al. 1980; E. Shapiro et al. 1989; R. Shapiro 1989b). The internal
      images of the adolescent held by family members appear to reflect healthy as well
      as pathological functioning of adolescent-family systems (Feldman and Guttman
      1984; E. Shapiro 1982; Young 1991).

PMID- 7800774
TI  - Social interaction and symptom sequences: a case study of orofacial bradykinesia
      exacerbation in Parkinson's disease during negative marital interaction.
AB  - Evidence is rapidly accumulating that disease symptoms are influenced by
      psychological factors, and most potently, by familial relationships. This case
      study demonstrated the detrimental influence of negative marital interaction on
      orofacial bradykinesia and speech productivity in a 74 year old male Parkinson's
      disease patient. An increase in bradykinesia symptoms followed a series of
      specific negative comments by the wife during a conversation; these symptoms
      showed partial reversal during a subsequent conversation with a lab assistant.
      The analytic method and data summary strategies used to determine this
      relationship are discussed relative to their possible utility for other
      disorders.

PMID- 7800775
TI  - Neurological trauma and family functioning: toward a social neuropsychology.
AB  - Griffin and Greene ("Social Interaction and Symptom Sequences," this issue)
      present evidence linking patterns of family interaction with the expression of
      disease symptoms, in this case orofacial bradykinesia in a patient with
      Parkinson's disease. They argue that symptom expression may be influenced by
      family interaction for many diseases or chronic conditions and advocate the use
      of behavioral observation and microanalytic coding of behavior sequences as a
      means of studying this linkage. They note that the success of this approach will
      depend on the temporal characteristics of symptom fluctuation and suggest that
      observational strategies will be primarily useful for studying symptoms that
      fluctuate across seconds or minutes rather than across days. What kinds of
      conditions might this include? Griffin and Greene mention three categories: (1)
      mental and emotional disorders; (2) chronic pain; (3) neurological conditions.

PMID- 7800776
TI  - Current concepts in the treatment of schizophrenia.

PMID- 7800777
TI  - Passage and significance of the 1944 Public Health Service Act.

PMID- 7800778
TI  - The Public Health Service and the nation's health care in the post-World War II
      era.

PMID- 7800779
TI  - The Gillis W. Long Hansen's Disease Center at Carville.

PMID- 7800780
TI  - Social and legal factors related to drug abuse in the United States and Japan.
AB  - This article is an overview of social and legal differences in the United States
      and in Japan that are related to patterns of current drug abuse epidemics in
      these countries. These two nations have drug abuse problems with different
      histories and take different approaches currently to handling illicit drug
      marketing and use. Histories of opiate and cocaine abuse in the United States and
      of stimulant and inhalant abuse in Japan are discussed. The United States has
      experienced three heroin epidemics in the last three decades; cocaine addiction
      began to merit national concern by the end of the 1980s. In Japan, the first
      methamphetamine epidemic began after World War II; it was controlled in the
      1950s. The current inhalant epidemic began in the late 1960s and was followed by
      the second methamphetamine epidemic that began in 1970; both are continuing to
      the present. The criminal justice system is always given first consideration when
      assessing societal measures employed to reduce drug use. Legal penalties for
      illicit drug offenses reflect the societal differences of these two nations with
      respect to the seriousness of particular types of crimes. Characteristics of the
      health care system of a nation may also influence patterns of drug abuse,
      particularly where functions of criminal justice and health care systems overlap.
      Health care systems in the United States and in Japan are based on different
      treatment philosophies and patients' expectations; these differences are
      discussed along with explanations of their potential influence on the
      epidemiology of drug abuse.

PMID- 7800781
TI  - Lower legal blood alcohol limits for young drivers.
AB  - To reduce the involvement of young drivers in alcohol-related crashes, 29 States
      and the District of Columbia have established lower legal blood alcohol limits
      for drivers younger than age 21 than for adult drivers. Of these, 12 lowered the
      legal limit for young people prior to 1991. To assess the impact, these 12 States
      were paired for comparison with 12 nearby States matched for legal drinking age
      and timing of changes in that law. Among drivers ages 15-20, fatal crashes
      involving a single vehicle at night are three times more likely than other fatal
      crashes to be alcohol-related. Whether the proportion of fatal crashes that
      involved single vehicles at night declined more among young drivers targeted by
      lower blood alcohol limits than among young drivers of the same age in comparison
      States was examined. The maximum available equal number of pre- and post-law
      years were compared in each pair of States. During the post-law period, the
      proportion of fatal crashes that involved single vehicles at night declined 16
      percent among young drivers targeted by lower blood alcohol laws, whereas it rose
      1 percent among drivers of the same age in comparison States where blood alcohol
      limits were not changed (P < .001). Among adults, the proportion of fatal
      nocturnal crashes that involved single vehicles declined 5 percent in the group
      of States with the lowered levels for young people during the period after the
      law was enacted and 6 percent in the group of neighboring comparison States. The
      proportion of fatal crashes that involved single vehicles at night declined 22
      percent among drivers in States with .00 percent limits, whereas it declined only
      2 percent among drivers of the same age in comparison States (P <.003). Among
      those targeted by .02 percent BAL limits, the proportion of fatal crashes that
      involved single vehicles at night declined 17 percent. It rose 4 percent in
      comparison States(P = .005). No significant difference appeared between States
      that lowered blood alcohol levels to the range of .04-.06 percent relative to
      comparison States.If all States adopted .00 or .02 percent limits for drivers
      ages 15-20, at least 375 fatal single vehicle crashes at night would be prevented
      each year.

PMID- 7800782
TI  - Antibiotic therapy for Lyme disease in Maryland.
AB  - The recommended treatment of Lyme disease is evolving and important questions
      remain unanswered, such as (a) Are inexpensive oral regimens effective in curing
      acute illness and preventing arthritic, neurologic, and cardiac manifestations or
      are much more costly, and potentially toxic, intravenous antibiotics required?
      (b) Are relatively short 2- to 3-week courses of antibiotics sufficient or are
      prolonged regimens of a month, or more, better? This study reviews antibiotic
      therapy prescribed by Maryland physicians for the 283 cases reported in 1991 that
      meet the Centers for Disease Control and Prevention's case definition for Lyme
      disease. The purpose of the review was to obtain baseline information on the
      antibiotics being used by physicians in practice to treat patients that they
      believe have Lyme disease. The most frequently prescribed antibiotics for either
      the 60 percent of patients presenting with erythema migrans or the 40 percent
      with arthritic, neurologic, or cardiac manifestations were oral doxycycline (47
      percent), tetracycline (11 percent), and amoxicillin (13 percent). Seventy-one
      percent of therapeutic courses were for 2 to 3 weeks. Amoxicillin was used in two
      thirds of children younger than 8 years. Sixty (21 percent) received intravenous
      therapy, of which ceftriaxone, with or without other antibiotics, was almost
      always (95 percent) used. Intravenous therapy was more frequently given to those
      with arthritic, neurologic, and cardiac manifestations than to those with
      erythema migrans (odds ratio = 3.7) and to those with these systemic symptoms
      along with erythema migrans than to those with erythema migrans alone (odds ratio
      = 3.8). The average course was 2 days longer in treating those with arthritic,
      neurologic, or cardiac manifestations than in treating those with erythema
      migrans alone(P = 0.05).An epidemiologic assessment of antibiotics prescribed by
      the physicians in Maryland to treat Lyme disease in 1991 shows the choices,
      dosage, and duration of drugs generally followed those most frequently
      recommended in the literature. Also, it shows that efforts to educate physicians
      should be directed more towards the diagnosis rather than the treatment of Lyme
      disease.

PMID- 7800783
TI  - Age-specific incidence of chickenpox.
AB  - Because licensure of a chickenpox (varicella) vaccine is likely soon, it is
      important to ascertain the age-specific incidence of chickenpox. Increasing
      vaccine coverage and a resulting decrease in transmission may result in an
      accumulation of susceptible adults, followed by a shift of incidence into those
      older age groups in future years. Valid baseline age-specific incidence will make
      it possible to detect this phenomenon. Two studies were conducted in Kentucky to
      assess age-specific incidence of chickenpox. The first assessed chickenpox
      occurrence in two consecutive school-year cohorts of children from a
      geographically representative sample of Kentucky primary schools. The second
      gathered information from household members of those persons interviewed in the
      Behavioral Risk Factor Surveillance System telephone survey. The age-specific
      rates are remarkably similar between studies. Rates peak during the preschool and
      kindergarten years (ages 3-6). Approximately 20 percent of children remain
      susceptible to chickenpox after age 8 in both studies. The results from these two
      surveys will be valuable baselines for comparison with findings in incidence
      studies that will be performed after vaccine licensure.

PMID- 7800785
TI  - Universities as resources to state health agencies.
AB  - In a survey of the 50 State health agencies in the spring of 1992, officials were
      asked about their manpower and research needs in the specific areas of
      administration, behavioral and social science, education and information,
      environmental health, environmental protection, epidemiology, laboratory, law,
      occupational health, policy and planning, and statistics. In all, 40 agencies (80
      percent) responded. Indepth telephone interviews to determine whether
      universities and schools and graduate programs in public health filled these
      needs completed the data collection process. Agency officials indicated that
      their resources were least adequate in environmental protection, behavioral and
      social science, and occupational health. They did not feel their research needs
      were being met. There was a general feeling that universities and schools and
      programs in public health have different agendas than State agencies and that
      practical solutions to the shortage of research resources are not forthcoming
      from these sources. Suggestions are made as to what can be done to improve
      relationships between those who train public health personnel and those who
      employ them.

PMID- 7800786
TI  - High prevalence of overweight and short stature among Head Start children in
      Massachusetts.
AB  - The Head Start Program measures children's heights and weights to screen for
      growth problems such as obesity, wasting, and short stature. At present, little
      public health use is made of these data. In this paper, the authors present
      serial cross-sectional nutrition surveillance data from Massachusetts Head Start
      Programs. Nonrandom samples of local Head Start Programs provided annual
      screening data from 1988 to 1991 on an average of 2,664 children per year. Height
      and weight measurements were compared with National Center for Health Statistics
      (NCHS) reference populations. On average, 87 percent of the children were 36 to
      59 months of age and 51 percent were white. From 7.3 to 8.8 percent of children
      were below the 5th percentile of height for age each year, and from 1.2 to 3.3
      percent were underweight, with weight below the 5th percentile for height (P <
      0.05 compared with NCHS population). In each year overweight (weight for height
      above the 95th percentile) was most prevalent, ranging from 9.6 percent to 13.3
      percent (P < 0.05 compared with NCHS) and demonstrating a statistically
      significant upward trend over the 4 years of study (chi-square = 9.21, P < 0.01).
      The prevalence of overweight and short stature varied by race and ethnicity. A
      statistically significant upward trend in overweight was seen among Hispanic
      children (chi-square = 5.99, P < 0.05). Also, children who were 48 months of age
      or older were more likely than younger children to be overweight (P < 0.05). The
      prevalence of short stature did not vary significantly by year, sex, or age. The
      authors conclude that children attending Head Start Programs in Massachusetts are
      at risk for short stature and are at increasing risk of obesity. These risks vary
      by race and ethnicity. Further research is needed to determine the
      generalizability of these findings to other regions and to evaluate social and
      behavioral correlates of poor nutrition outcomes among Head Start children.

PMID- 7800784
TI  - Profile of HIV seropositive inmates diagnosed in Maryland's state correctional
      system.
AB  - Correctional systems increasingly serve as the health care nexus for the initial
      diagnosis and treatment of human immunodeficiency virus (HIV) infection,
      particularly among traditionally underserved populations. A survey was conducted
      to describe the clinical profile of inmates in a State correctional system
      diagnosed with HIV infection by various testing strategies. Approximately 50
      percent of the inmates diagnosed were potential candidates for anti-retroviral
      therapy, and 17 percent were severely immunocompromised. Implementation of
      voluntary HIV testing at prison entry increased the number of persons identified
      with HIV infection; however, since volunteers at entry had higher CD4 cell counts
      compared with infected inmates diagnosed by other methods, there was not a
      parallel increase in the percentage requiring immediate medical treatment. These
      data are important for planning medical resources in the correctional setting and
      underscore the opportunity to provide prevention and therapy for a vulnerable
      population with HIV infection. Public health interventions within the
      correctional setting have a broader societal impact, since most infected inmates
      serve short sentences (median, 3 years). Clinical case management is critical for
      inmates with HIV infection released to the community so that linkages with
      primary care providers and support services can be established.

PMID- 7800787
TI  - The Minnesota Prenatal Care Coordination Project: successes and obstacles.
AB  - The Minnesota Prenatal Care Coordination Project was a statewide effort to
      present systematically education and technical support to providers as they
      implemented the Minnesota Prenatal Care Initiative for expanded services to high
      risk women. Educational methods included holding 12 regional workshops throughout
      the State, one-to-one contacts by nurse consultants, and newsletters and a
      guidebook (manual) were distributed to reach community providers. Analysis of the
      implementation was conducted using site visits, interviews with providers, and
      reviews of medical records, claims data, and other project documents. Successes
      in the first year were a twofold increase in the numbers of Medicaid-enrolled
      women who received risk assessment and enhanced services, more than one-third
      increase in provider participation, greater collaboration among multidisciplinary
      providers at the community level, and improved communication between State and
      local health care agencies. Obstacles included provider resistance to changes in
      practice, dissatisfaction with the enhanced services package and level of
      reimbursement, and problems with implementation protocols. The project
      demonstrated that prenatal care providers will change; they will improve
      practices and collaboration as a result of personalized education and support.

PMID- 7800788
TI  - The health burden of diabetes for the elderly in four communities.
AB  - Although diabetes is a common health problem of the elderly, the impact of
      diabetes on health and functioning in older persons is not well established. The
      purpose of this analysis was to identify health conditions accompanying diabetes
      in four samples of community dwelling elderly people. The study samples consisted
      of 13,601 persons ages 65 or older who participated in the Established
      Populations for Epidemiologic Studies in the Elderly (EPESE). Extensive
      interviews were conducted in respondents' homes to obtain information on diabetes
      and other health conditions, health behaviors, use of health services, and
      demographic characteristics. A lifetime history of diabetes was reported by 14
      percent of respondents. The prevalence of the disease was higher in blacks than
      whites, especially among women. Persons with diabetes were more likely to report
      myocardial infarction, stroke, vision problems, physical disability,
      incontinence, and nursing home stays than persons without diabetes, but the
      diabetics were less likely to consume alcohol or tobacco. Those with diabetes
      were only slightly heavier than those without diabetes at the time of the
      interview. However, body mass at age 50 was substantially greater among persons
      with diabetes. Associations between diabetes and other health conditions and
      behaviors were similar for whites and blacks. These results show that aged
      persons with diabetes experience substantial comorbidity, which has important
      ramifications for functioning and survival.

PMID- 7800789
TI  - Cancer control planning and establishment of priorities for intervention by a
      state health department.
AB  - A number of data sources routinely available to State health departments were
      analyzed as part of a State health department cancer control planning effort.
      This planning effort consisted of seven steps; the most challenging one was the
      establishment of priorities for cancer control interventions. Using data from
      available sources, however, a framework for prioritizing potential cancer control
      interventions as well as choosing a geographic area in which to implement
      selected interventions was developed. Factors considered in this framework for
      setting intervention priorities included the magnitude of the problem; the
      existence of scientific consensus regarding the efficacy of intervention
      techniques; the availability of data needed to plan, implement, and evaluate an
      intervention; the availability of resources within communities to implement an
      intervention; and the existence of public demand for the intervention. The
      development and use of this cancer control planning model and framework for
      setting cancer control intervention priorities in New York State are described in
      this paper. In using this planning model and framework for setting priorities,
      quantitative elements were found to be most necessary to define problems, but
      qualitative elements were most crucial for decision making.

PMID- 7800790
TI  - Education of rural physicians about breast cancer through an oncology outreach
      program.
AB  - In 1990, the Rural Illinois Cancer Consortium initiated an intervention in the
      management of breast cancer for all rural hospitals. Regional data from a 12
      county area were used to identify issues and develop an intervention emphasis.
      The data suggested two management issues: eliminate unilateral diagnostic
      mammography and increase the number of patients that have their tumor staged. The
      intervention involved seminars to provide feedback to physicians on management of
      breast cancer patients in the region. A series of personalized mailings
      emphasizing the intervention message were also deployed. Although data are not
      yet available to measure the intervention impact, immediate feedback on the
      interventions was sought through a physician survey and several process measures.
      The immediate feedback measures were assessed. These measures were the
      penetration of the rural hospital seminars, physician behavior self-reported by
      mail survey, and number of inquiries to the Physician Data Query. Each of the
      nine hospitals held a seminar, and 39 percent of the rural physicians treating
      breast cancer patients attended. Survey data showed physician behavior change in
      the desired direction, compared with data from the baseline medical record audit
      conducted in 1986-87. Intervention feedback was useful in defining the
      implementation success of the interventions. The outcome evaluation, based on
      medical record audits, is in progress.

PMID- 7800791
TI  - A rural-urban comparative study of nonphysician providers in community and
      migrant health centers.
AB  - This is a study of the employment of nonphysician providers--nurse practitioners,
      physician assistants, and certified nurse midwives--in both rural and urban
      Community and Migrant Health Centers and of factors associated with their
      employment, based on a 1991 national survey of 383 Centers. Results of the survey
      suggest that nonphysician providers, in particular nurse practitioners and
      certified nurse midwives, primarily serve as physician substitutes, and are more
      likely to be employed by Centers that are larger and have affiliations with
      nonphysician provider training programs. Rural or urban location is not
      significantly related to the employment of nonphysician providers after
      controlling for center size. The fact that rural centers employ fewer
      nonphysician providers than urban centers can primarily be accounted for by their
      relatively small size, rather than a lack of interest. These findings demonstrate
      that the use of nonphysician providers is an important way both to achieve cost
      containment and improve access to primary care for those residing in medically
      underserved areas.

PMID- 7800792
TI  - The sale of alcoholic beverages to minors.
AB  - This study reports the findings of a field trial designed to assess the extent of
      alcohol sales to minors in one county in northwest New Jersey. Two 19-year-old
      males were successful in purchasing alcoholic beverages in 27 of 46 (58.7
      percent) establishments visited. On the following day, 23 of the establishments
      that sold the alcohol were visited again and, on this occasion, 18 (78.3 percent)
      sold alcohol to the minor. This study supports the findings from surveys that
      show that underage drinkers can obtain alcohol with ease. Many community groups
      are now taking action to rectify this situation, and data of the type reported in
      this paper can be used to assess the effectiveness of their actions.

PMID- 7800793
TI  - Public health applications of Hansen's disease research and treatment.
AB  - Because of the similarities in causative agents of Hansen's disease and
      tuberculosis, Hansen's disease research is now being used in the identification,
      treatment, and prevention of tuberculosis. Numerous studies are under way to
      screen and develop new drugs to combat the threat of multiple drug-resistant
      tuberculosis. Additional studies focus on factors to reduce the transmission of
      tuberculosis and on the development of techniques for early diagnosis and
      identification of drug resistance. Advances in Hansen's disease research and
      treatment also are being applied to the prevention of ulcers and amputations in
      diabetics and others without protective sensation in their feet. The Lower
      Extremity Amputation Prevention Program, developed at the Gillis W. Long Hansen's
      Disease Center in Carville, LA, is a multidisciplinary approach that includes
      screening, risk assessment, and the development of a treatment plan with an
      emphasis on patient involvement. Expected to prevent up to 90 percent of diabetes
      related amputations, the program is being implemented in Jackson, MS, in a
      community-based diabetic foot program and will be replicated throughout the
      United States.

PMID- 7800794
TI  - Behavioral risk factors of Chippewa Indians living on Wisconsin reservations.
AB  - Behavioral risk factors and chronic disease death rates vary markedly among the
      numerous American Indian tribes. Local data on prevalence of risk factors are
      important in determining effective community-based interventions. The authors
      conducted an in-person survey to ascertain the prevalence of behavioral risk
      factors among members of the Chippewa tribe living on reservations in Wisconsin.
      A total of 465 Chippewa adults were randomly selected from tribal registries and
      invited to participate in the study. Of these, 175 (38 percent) participated. To
      characterize nonrespondents, 75 nonrespondents were randomly selected and
      aggressively followed up. The authors compared their results with data from the
      1989 Wisconsin Behavioral Risk Factor Surveillance System. Chippewa respondents
      reported high levels of obesity and tobacco use. No significant differences
      existed between the original survey and followback of nonrespondents. Compared
      with respondents who had telephones, those without telephones were significantly
      more likely to be unemployed, to be a current smoker or drinker, and to report
      nonuse of seatbelts. Compared with the general Wisconsin population, Chippewa
      adults appear to have higher prevalences of several chronic disease and injury
      risk factors. The original survey methodology, despite the low response rate,
      appeared to give a more accurate (less biased) estimate of risk factor
      prevalences than would have been achieved by a telephone survey.

PMID- 7800796
TI  - [Percutaneous transluminal angioplasty update].

PMID- 7800795
TI  - The report to Congress on the appropriate federal role in assuring access by
      medical students, residents, and practicing physicians to adequate training in
      nutrition.
AB  - The Congress has had a long-time concern about the adequacy of nutrition
      education provided medical students and physicians during their training.
      Attempts over three decades to address this deficiency have been largely
      ineffective. Yet, recent changes in the delivery of health care from inpatient to
      outpatient services require physicians be competent in both applied nutrition and
      patient counseling. The importance of patient counseling is underscored by the
      surveys of the National Center for Health Statistics which reveal that overweight
      for the U.S. population has increased between the early 60s and the late 80s.
      These findings suggest that the Healthy People 2000 objective of reducing the
      prevalence of overweight may not be met. Congress evidenced its concern about the
      nutrition education in the medical curriculum in Section 302 of the National
      Nutrition Monitoring and Related Research Act of 1990 that required a report on
      the subject from the Secretary of Health and Human Services. The Division of
      Medicine in the Health Resources and Services Administration, an agency of the
      Public Health Service, responded by compiling the report. The report to Congress
      focuses on two issues--why it has been so difficult to increase the nutrition
      content of medical school curriculums and, if the Federal Government intervenes,
      what strategies might be effective.

PMID- 7800797
TI  - [US Doppler guide wire. Initial experiences in angioplasty of peripheral blood
      vessels].
AB  - Forty-two patients underwent endoluminal Doppler examination of blood flow
      velocity proximally, at the stenosis and distal to it by means of a 0.018 in.
      Doppler guide wire. The method was found to be an accurate tool for documentation
      of a wide spectrum of stenoses of different morphology. The changes induced by
      percutaneous transluminal angioplasty (PTA)-hemodynamic changes as well as
      vascular wall lesions-could be documented precisely. Remaining stenoses after PTA
      were precisely verified as compared to angiography. In multiple stenoses or in
      stenoses with pure run-off, the hemodynamic significance of the lesion was
      evaluated. Intravascular Doppler flow measurement is valuable in angiographically
      imprecise cases. The method fits well into the angiographic routine examination.

PMID- 7800798
TI  - [Stent angioplasty of the intrarenal aorta and aortic bifurcation. Clinical and
      angiographical results of a prospective study].
AB  - PURPOSE: The study was carried out to evaluate clinical and technical success,
      early and late complications and patency rates after stent angioplasty of
      atherosclerotic stenoses and occlusions of the infrarenal abdominal aorta and
      aortic bifurcation. PATIENTS AND METHODS: This was a prospective study in 20
      consecutive patients treated by implantation of balloon-expandable stents. All
      patients were followed-up after 6 and 12 months and at yearly intervals
      thereafter by physical examination, Doppler sonography and angiography. RESULTS:
      Nineteen of 20 patients had clinical and technical success. In two patients
      clinically relevant complications occurred. During a mean observation time of 19
      months (range 3-51 months) restenosis occurred in one stent after 15 months and
      was successfully treated by balloon angioplasty. Two patients became symptomatic
      again due to new atherosclerotic disease. CONCLUSIONS: Percutaneous stent
      angioplasty of the infrarenal aorta and aortic bifurcation yields high immediate
      and mid-term success rates with primary patency of 90% and secondary patency of
      95%. These results are slightly better than those with balloon angioplasty, but
      the limited number of patients in our and others' studies does not yet justify
      general recommendations.

PMID- 7800799
TI  - [Transluminal stent prosthesis in aneurysm of the abdominal aorta. Initial
      experiences with a new procedure].
AB  - We report our initial experience with percutaneous treatment of aortic aneurysms
      in three patients by stent grafts. A newly developed balloon-expandable Palmaz
      stent in combination with predilated PTFE was used. In two patients a tube-type
      reconstruction was performed and in the third patient an aorto-bi-iliac
      reconstruction. Total exclusion of the aneurysm was achieved in one patient. The
      other two patients had an acceptably minimal amount of residual perfusion, which
      slightly decreased during the follow-up period of 6 months. One iliac rupture
      occurred that was immediately treated by insertion of another stent graft. This
      study confirms the feasibility of such a concept. Further investigation is
      warranted.

PMID- 7800800
TI  - [Endovascular radioprevention of intimal hyperplasia after percutaneous
      transluminal angioplasty of peripheral blood vessels].
AB  - The prognosis of interventionally treated arterial occlusive vessel disease in
      peripheral arteries is not significantly better with the use of stents than with
      percutaneous transluminar angioplasty. The rate of restenosis or reocclusion in
      dilated or recanalized and stented peripheral arteries is reported as up to 40%,
      depending on location and author. In the early phase thrombotic processes are
      responsible which then demonstrate histologically confirmed intimal hyperplasia.
      On the basis of many years of radiotherapy experience in the treatment of benign
      hyperplastic tissue alterations, brachytherapy could be introduced as a method
      for prophylaxis of vessel restenoses. The early difficulties with this method
      were due to the inadequacies of the equipment. The development of small radiation
      sources with high specific activity now enables these target volumes to be
      reached. The clinical experience so far indicates high efficiency of this method.
      It can be expected that the range of indications for adjuvant endoluminal
      irradiation will broaden in the future.

PMID- 7800801
TI  - [Intervention and clinical aspects combined with endovascular irradiation of
      intimal hyperplasia of the vascular system].
AB  - After implantation of stents in femoropopliteal arteries we found restenosis or
      occlusions by intimal hyperplasia in up to 40% especially in the hunter's
      channel. Repeated balloon angioplasty and prophylactic endovascular radiotherapy
      with a surface dose of 12 Gy in the vessel wall using an iridium 192 source in
      the same investigational session is a new technique to reduce or eliminate
      further recurrence. All 18 patients had developed recurrent stenoses or
      occlusions 6-8 months after original stent implantations. The patients have not
      redeveloped recurrent obstructions after this treatment, which up to date showed
      no short term or long term complications. We conclude that the encouraging
      results of this pilot study justify further randomized trials.

PMID- 7800802
TI  - [Leiomyomatosis of the esophagus].
AB  - A rare case of dysphagia caused by leiomyomatosis of the esophagus is presented.
      Esophageal leiomyomatosis is triggered by diffuse proliferation of smooth muscle
      cells in the wall of the entire esophagus. Only 1.0% of all tumors of the
      esophagus are benign lesions; 0.4% of all esophageal neoplasms are leiomyomas.
      Only a few cases of leiomyomatosis-a special form of diffuse leiomyomas-have been
      described so far in the literature. Modern diagnostic imaging techniques such as
      CT and MR are described in esophageal leiomyomatosis.

PMID- 7800803
TI  - [Mediastinal actinomycosis with formation of an esophagotracheal fistula. A case
      report].
AB  - Before antibiotics were available, actinomycosis was the most commonly diagnosed
      "fungal disease" of the lung because of its morphological similarity to true
      fungi. At that time actinomycosis presented a fairly typical clinical picture of
      empyema thoracis and sinus tracts in the chest wall. Nowadays it has become a
      rare infectious disease that is usually caused by the bacterium Actinomyces
      israelii and is amenable to treatment by most antibiotics available today. The
      following report describes the case of a 59-year-old man with an uncommon
      mediastinal actinomycosis that caused an oesophagotracheal fistula. This
      complication may develop due to the necrotizing inflammatory process that is
      typical for actinomycosis. With regard to the literature, the clinical
      manifestations of the disease and diagnostic and therapeutic considerations are
      discussed.

PMID- 7800804
TI  - [Band-like lucency image in the digital radiogram before CT].

PMID- 7800806
TI  - [CD-ROM for radiologic literature research].
AB  - A CD-ROM containing the indexed radiological literature, including abstracts
      based on the MEDLINE from the last 10 years, is available with the Knowledge
      Finder RAD-LINE. The software can be used under DOS, Windows and Apple Macintosh.
      It is very user-friendly and enables efficient searches to be carried out in the
      literature based on free text and additional criteria such as key words, author
      names, time periods, journals and language. For the first time the CD permits
      quick, direct access to the relevant radiological literature for a greater period
      of time and is a very helpful tool for scientific work as well as a comfortable
      means of staying abreast on current topics.

PMID- 7800805
TI  - [Acute therapy of anaphylactoid reactions. Results of an interdisciplinary
      consensus conference].

PMID- 7800807
TI  - The self-organizing brain: from growth cones to functional networks. Proceedings
      of the 18th International Summer School of Brain Research. The Netherlands, 23-27
      August 1993.

PMID- 7800808
TI  - Geometrical and topological characteristics in the dendritic development of
      cortical pyramidal and non-pyramidal neurons.

PMID- 7800809
TI  - Electrotonic properties of passive dendritic trees--effect of dendritic topology.

PMID- 7800810
TI  - Exploring the computational capabilities of single neurons by continuous cable
      modelling.

PMID- 7800811
TI  - Theoretical models for describing neural signal transduction.

PMID- 7800812
TI  - Intrinsic neuronal physiology and the functions, dysfunctions and development of
      neocortex.

PMID- 7800813
TI  - Development of projection neurons of the mammalian cerebral cortex.

PMID- 7800814
TI  - Naturally occurring and axotomy-induced motoneuron death and its prevention by
      neurotrophic agents: a comparison between chick and mouse.
AB  - Neuronal cell death is an important regressive event during the normal
      development of the peripheral and central nervous systems of many vertebrate and
      invertebrate species. Furthermore, when neurons are deprived of their target
      following axonal injury (axotomy) during embryonic, fetal, or early postnatal
      development, they undergo massive cell death. Both naturally occurring and
      axotomy-induced neuronal cell death can be prevented by treatment with growth
      factors or neurotrophic agents. Naturally occurring cell death of spinal MNs has
      been extensively studied in both avians and mammals. However, compared with
      mammals, there is little information on the effects of axotomy in avian species
      and it is not known whether trophic agents can modify axotomy-induced death in
      avian MNs. It is also not known whether trophic/growth factors can promote the in
      vivo survival of mammalian MNs during the period of naturally occurring cell
      death. We have examined (1) the time course of axotomy-induced death of lumbar
      spinal MNs in chick and mouse, and (2) the survival-promoting activity of a
      number of previously characterized growth and trophic factors on both programmed
      and axotomy-induced MN death in these two species. We show that axotomy performed
      on, or prior to, E12 in the chick results in a rapid decrease (i.e. 50%) in MN
      numbers within 3-4 days postsurgery, whereas these cells were able to survive for
      up to 1 week following axotomy on E14. By contrast, mouse MNs remained vulnerable
      to axotomy for at least 5 days after birth.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7800815
TI  - Synaptic development of the cerebral cortex: implications for learning, memory,
      and mental illness.

PMID- 7800816
TI  - Activity-dependent neurite outgrowth and neural network development.

PMID- 7800817
TI  - gamma-Aminobutyric acid (GABA): a fast excitatory transmitter which may regulate
      the development of hippocampal neurones in early postnatal life.
AB  - The properties of neonatal GABAergic synapses were investigated in neurones of
      the hippocampal CA3 region. GABA, acting on GABAA receptors, provides most of the
      excitatory drive on immature CA3 pyramidal neurones at an early stage of
      development, whereas glutamatergic synapses (in particular, those mediated by
      AMPA receptors) are mostly quiescent. Thus, during the first postnatal week of
      life, bicuculline fully blocked spontaneous and evoked depolarising potentials,
      and GABAA receptor agonists depolarised CA3 pyramidal neurones. GABAA mediated
      currents also had a reduced sensitivity to benzodiazepines. In the presence of
      bicuculline, between P0 and P4, increasing the stimulus strength reveals an
      excitatory postsynaptic potential which is mostly mediated by NMDA receptors.
      During the same developmental period, pre- (but not post) synaptic GABAB
      inhibition is present. Intracellular injections of biocytin showed that the
      axonal network of the GABAergic interneurones is well developed at birth, whereas
      the pyramidal recurrent collaterals are only beginning to develop. Finally,
      chronic bicuculline treatment of hippocampal neurones in culture reduced the
      extent of neuritic arborisation, suggesting that GABA acts as a trophic factor in
      that period. In conclusion, it is suggested that during the first postnatal week
      of life, when excitatory inputs are still poorly developed, GABAA receptors
      provide the excitatory drive necessary for pyramidal cell outgrowth. Starting
      from the end of the first postnatal week of life, when excitatory inputs are well
      developed, GABA (acting on both GABAA and GABAB receptors) will hyperpolarise the
      CA3 pyramidal neurones and, as in the adult, will prevent excessive neuronal
      discharges. Our electrophysiological and morphological studies have shown that
      hippocampal GABAergic interneurones are in a unique position to modulate the
      development of CA3 pyramidal neurones. Developing neurones require a certain
      degree of membrane depolarisation, and a consequent rise in intracellular
      calcium, for stimulating neurite outgrowth; the GABAergic network, which develops
      prior to the glutamatergic one, appears to provide this depolarisation. Starting
      from the end of the first postnatal week of life, at a time when excitatory
      pathways are developing, GABA (acting on both GABAA and GABAB receptors) would
      reverse its action, and start to play its well-known role as an inhibitory
      neurotransmitter.

PMID- 7800818
TI  - Regulation of N-methyl-D-aspartate (NMDA) receptor function during the
      rearrangement of developing neuronal connections.
AB  - There is evidence from a number of studies that the molecular and biophysical
      properties of NMDA receptors are altered during normal development. A temporal
      correlation with changes in NMDA receptor efficacy and periods of synaptic
      plasticity has been demonstrated in several systems, suggesting that NMDA
      receptors have a critical function in determining periods of synaptic plasticity.
      Data from our laboratory demonstrate reduced NMDA sensitivity of the tectal
      evoked potential following chronic application of NMDA to the tadpole tectum, a
      treatment that may mimic a naturally occurring mechanism for limiting neuronal
      plasticity to certain stages of development. Our analysis of the expression
      pattern of mRNA coding for various glutamate receptor subunits in the rat
      retinocollicular system establishes that differential regulation of NMDA receptor
      subunits at the mRNA level could be a molecular basis for changes in biophysical
      and pharmacological properties of the NMDA receptor complex. However, even though
      the NMDA receptor is the best studied candidate to function as a 'plasticity
      switch', there are large gaps in our understanding of the complete set of factors
      that control the ability of synapses to rearrange during development.

PMID- 7800819
TI  - Role of the visual environment in the formation of receptive fields according to
      the BCM theory.

PMID- 7800820
TI  - Reciprocity of structure-function relations in developing neural networks: the
      Odyssey of a self-organizing brain through research fads, fallacies and
      prospects.

PMID- 7800821
TI  - Models of activity-dependent neural development.
AB  - What makes a useful model of neural development? One important contribution of
      modeling is to demonstrate that proposed biological mechanisms can be sufficient
      to account for experimental results. The Von der Malsburg model is a classic
      example. But such demonstrations alone do not provide tools to experimentally
      distinguish one mechanism from another. To draw such distinctions, the connection
      between measurable biological quantities and developmental outcomes must be
      established. Perhaps the most important task for the future of developmental
      modeling is to deepen the connection between theory and experiment.
      Experimentally, this requires detailed and difficult measurements or experimental
      perturbations of the correlations among inputs and the intracortical connectivity
      existing during development. Simultaneous measurement of the maps of spatial
      phase and orientation of mature simple cells will provide important information
      for the understanding of orientation column development. Theoretically, the
      number of open problems is enormous. How will inclusion of additional plasticity
      mechanisms, such as sprouting and retraction of synapses or plasticity of
      intracortical connections, alter the analytical understanding thus far achieved?
      What precisely determines the width of orientation columns in the model presented
      here? Can the relationship between ocular dominance and orientation columns be
      understood from developmental rules in a testable way? The existing framework may
      be extended to a three-dimensional cortex and to more complex models of
      intracortical connectivity. It may also be applied to other developmental
      phenomena including the development of lamination in the LGN (Shatz and Stryker,
      1988; Hahm et al., 1991), the formation of visual maps in experimentally altered
      auditory cortex (Roe et al., 1990, 1992), and the mapping of visual and auditory
      maps in the optic tectum (Knudsen and Brainard, 1991; Brainard and Knudsen,
      1993). For each system the goal is to develop testable predictions as to the
      patterns of activity and connectivity that could or could not lead to the results
      observed given a proposed mechanism of plasticity. Incorporation of deeper levels
      of biophysical realism will extend, deepen, and perhaps fundamentally alter the
      framework presented here. An important goal for the future will be to understand
      the computational and functional significance of developmental rules. Activity
      dependent, competitive mechanisms of synaptic plasticity appear to play an
      important role in many processes of late neural development, where an initially
      rough connectivity pattern refines to a precise, mature pattern. A prominent
      example is the formation of ocular dominance columns in the visual cortex of many
      mammals. These processes may be modeled at several levels.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 7800822
TI  - Role of chaotic dynamics in neural plasticity.
AB  - Mathematical models are essential for the study of complex neural systems at all
      levels of the hierarchy from macromolecules through neurons to brain systems. ANN
      are readily available, but most of them are inappropriate for modeling brain
      function in normal behavior, because they stem from studies of neural systems in
      anesthetized or paralyzed animals which are capable only of reflux output. That
      class of models lacks the goal-directed, self-organizing properties of neural
      systems in behaving animals. In contrast to the stability of ANN and their
      reliance on asymptotic convergence to steady states (point attractors) and
      periodic oscillations (limit cycle attractors), BNN are intrinsically unstable.
      They continuously generate 'spontaneous' aperiodic activity that manifests the
      operation of chaotic dynamics undergoing repeated state transitions. Observations
      on the activity patterns of sensory cortex reveal that the perceptual outputs of
      BNN are by construction of spatial patterns and dynamic trajectories and not by
      computation using symbolic representations. Chaotic dynamics plays essential
      roles both in the construction of perceptions and in the continuing update of
      cortical populations, which requires selective synaptic modification during
      associative learning and habituation. Simultaneous multichannel recording from
      the olfactory bulb and cortex has given the following experimental results. (1)
      The cortical activity that relates to the perception of a sensory stimulus is
      carried macroscopically by a smaller number of single neurons e.g. 'units',
      'feature detectors'. (2) The macroscopic activity reflects the meaning and
      significance of the stimulus for the experimental subject and not the stimulus as
      it is known to the observer. (3) The activity carries the meaning in spatial
      patterns, not in time series (the difference between a phonograph or radio and
      movie or TV). (4) The spatial patterns of activity that accompany previously
      learned stimuli or responses are changed by the introduction of new stimuli and
      also by modifications in reinforcement contingencies. There is no invariance in
      the memory store within the populations. (5) The patterns of activity are created
      by dynamic neural interactions in sensory cortex, not by registration or
      filtering of stimuli. There is no evidence for storage, retrieval, cross
      correlation or logical tree search. (6) The dynamics is chaotic, not merely
      noisy, so that each act of perception involves a new construction by the cortex
      not by mere information processing. From these findings we infer that chaotic
      dynamics plays a crucial role in the construction of the associational contexts
      comprising the memory systems of experimental subjects.

PMID- 7800823
TI  - Neural networks in the brain involved in memory and recall.
AB  - We have considered how the neuronal network architecture of the hippocampus may
      enable it to act as an intermediate term buffer store for recent memories, and
      how information may be recalled from it to the cerebral cortex using modified
      synapses in back-projection pathways from the hippocampus to the cerebral cortex.
      The recalled information in the cerebral neocortex could then be used by the
      neocortex in the formation of long-term memories, which is severely impaired by
      damage to the hippocampus.

PMID- 7800824
TI  - Categories of cortical structure.

PMID- 7800825
TI  - Growth cone motility: substratum-bound molecules, cytoplasmic [Ca2+] and Ca(2+)
      regulated proteins.

PMID- 7800826
TI  - Dynamics of local neuronal networks: control parameters and state bifurcations in
      epileptogenesis.
AB  - The aim of this overview is to present evidence that local neuronal networks
      (LNNs) are functionally organized in such a way that they behave as dynamic non
      linear systems that can exhibit multiple types of attractor and can present
      bifurcations between different attractors, depending on control parameters. To
      begin with, some of the theoretical concepts of non-linear dynamics and chaos are
      briefly presented. As a case study, we described the CA1 area of the hippocampus
      and the changes that the corresponding LNNs undergo during kindling
      epileptogenesis. During epileptic seizures, evidence exists for the presence of
      low-dimensional chaos, since the correlation dimension estimated from the
      corresponding EEG signals decreases dramatically from a large value,
      characteristic of the resting state, to a low value typical of deterministic
      chaos. We propose that, among other things, an important control parameter of the
      dynamics of this brain area is the balance between excitatory (E) and inhibitory
      (I) processes. We assume that this balance can be experimentally estimated by
      using a paired-pulse paradigm. Accordingly, we demonstrate that the paired-pulse
      response changes during kindling epileptogenesis in the sense that the E/I ratio
      increases in the course of the establishment of a kindled epileptogenic focus.
      This change in E/I leads to a shift in the operating point of the LNN moving it
      close to a bifurcation where a rapid state change takes place. In this way, the
      LNN dynamics can change more readily to the basin of attraction of a chaotic
      attractor than under normal conditions. This is in essence what makes the
      behavior of the LNN more sensitive to tetanus, and predicts the facilitated
      occurrence of epileptic seizures during kindling.

PMID- 7800827
TI  - Non-linear dynamics in neural networks.
AB  - A general framework for the analysis of neurons as stochastic, three
      dimensionally complex and non-linear units with a range of temporal properties is
      outlined, and a class of problems delineated. Some general mathematical
      properties of the resulting network are deduced, together with information
      theoretic questions to be pursued. In particular examples of the relevance of the
      nonlinear, temporal and stochastic properties of neurons in effective information
      processing are briefly outlined.

PMID- 7800828
TI  - Are there unifying principles underlying the generation of epileptic
      afterdischarges in vitro?
AB  - To find general principles in the cellular mechanisms of epileptogenesis, one
      must analyze experimental epilepsy models and determine what exists in common
      between them. We consider here afterdischarges in hippocampal slices induced
      using either (1) GABAA blockade (e.g. with bicuculline), (2) a bathing solution
      lacking Mg2+ ions (low Mg-induced epilepsy), or (3) 4-aminopyridine (4AP). By
      'afterdischarge' we mean an event that lasts hundreds of milliseconds or more,
      involving the synchronous firing of all the neurons in a population, shaped into
      a long initial burst and a series of one or more secondary bursts, and
      terminating in a prolonged afterhyperpolarization (AHP). We propose that the
      following features exists in common between these three experimental epilepsies:
      (1) recurrent excitatory synaptic connections; (2) sustained dendritic synaptic
      excitation, mediated by either AMPA or NMDA receptors, or both; (3) an intrinsic
      cellular response to sustained excitation, consisting of rhythmical dendritic
      bursts, primarily mediated by Ca spikes. In conclusion, if the picture outlined
      here proves correct, then the stereotypic appearance of epileptic afterdischarges
      -consisting of synchronized population bursts in series, whatever the network
      alteration leading to seizures--does indeed reflect a common set of mechanisms.
      The mechanisms cannot, apparently, be formulated in simple terms of this receptor
      or that receptor. Rather, we suggest, the recurrent excitatory synapses are able,
      under diverse circumstances, collectively to produce sustained dendritic
      conductances in neuronal populations. Pyramidal neurons, by virtue of their
      normal intrinsic membrane properties, respond to such sustained conductances with
      rhythmical bursts. The recurrent synapses, in a dual role, serve to maintain the
      synchrony of these bursts, and so shape the activity into a synchronized
      oscillation.

PMID- 7800829
TI  - Synchronization in neuronal transmission and its importance for information
      processing.

PMID- 7800830
TI  - Oscillatory and non-oscillatory synchronizations in the visual cortex and their
      possible roles in associations of visual features.
AB  - It was postulated that the perceived association of visual features is based on
      the synchronization of those neural signals that are activated by a coherent
      visual object. Two types of synchronized cortical signals were found by us in cat
      and monkey visual cortex, and were proposed as candidates for feature
      association: (1) stimulus-locked signals, evoked by transient retinal
      stimulation, and typically non-rhythmic; (2) oscillatory signals, induced by
      sustained stimuli, and typically not locked in their oscillation phases to
      stimulus events. Both types of signals can occur synchronously in those neurons
      that are activated by a common stimulus. Synchronized activities were found in
      paired recordings within vertical cortex columns, in separate columns of the same
      cortical area, and even between different cortical areas or hemispheres. The
      average phase difference between such common oscillatory events was typically
      close to zero (< 1 msec mean +/- 2 msec S.D.). For the dependence of
      synchronization from stimulus and receptive field properties, a preliminary
      'rule' can be given: the coherence of fast oscillations in separate cortical
      assemblies depends inversely on the 'coding distance' between the assemblies' RF
      properties, but directly on the degree of overlap between the assemblies'
      respective coding properties and the features of a common stimulus. This means
      that oscillatory events in any two assemblies, in the same or in different
      cortical areas or hemispheres, are more closely correlated the more similar are
      their receptive field properties, and the better a common stimulus activates the
      assemblies simultaneously. Our results can explain some neural mechanisms of
      perceptual feature-linking, including mutual enhancement among similar, spatially
      and temporally dispersed features, definitions of spatial and temporal
      continuity, scene segmentation, and figure-ground discrimination. We further
      propose that mutual enhancement and synchronization of cell activities are
      general principles of temporal coding by assemblies, that are also used within
      and among other sensory modalities as well as between cortical sensory and motor
      systems.

PMID- 7800831
TI  - Modelling the cerebellar Purkinje cell: experiments in computo.
AB  - Detailed compartmental models of neurons are useful tools for investigating
      neuronal properties and mechanisms that are not accessible to experimental
      procedures. If a rigorous approach is used in building the model, simulation
      studies can be as valuable as laboratory experimentation. As such, modelling
      becomes an additional method for exploring the function of neurons and nervous
      systems. As an example, a complex compartmental model with active dendritic
      membrane of a Purkinje cell is described. The response properties of the model to
      parallel fiber inputs were investigated. The model fired simple spikes in
      patterns comparable with those recorded from Purkinje cells in vivo. Synchronous
      activation of only 20 granule cell inputs was sufficient to generate a measurable
      response in simulated peri-stimulus histograms. This sensitivity to small
      excitatory inputs was caused by P-type Ca2+ channels in the dendritic membrane.
      Such P channels may also be present in the spine heads. Simulations suggest,
      however, that Ca2+ channels in spine heads cannot be activated by single parallel
      fiber inputs.

PMID- 7800832
TI  - Filopodia as detectors of environmental cues: signal integration through changes
      in growth cone calcium levels.

PMID- 7800833
TI  - Microtubule transport and assembly cooperate to generate the microtubule array of
      growing axons.
AB  - MTs are major architectural elements in growing axons. MTs overlap with each
      other along the axon, forming an array that is continuous from the cell body to
      the tip of the axon. The MT array constitutes a scaffolding that mechanically
      supports the elongate shape of the axon and also contributes directly to its
      shape. MTs also direct the transport of vesicular organelles between the cell
      body and the axon, and thereby determine, in part, the composition of the axon.
      In this article, I have discussed mechanisms involved in the elaboration of the
      MT array in growing axons, and I have emphasized the distinct but complementary
      roles of polymer transport mechanisms and local assembly dynamics. MTs for the
      axon originate in the cell body, and they are delivered to the axon by the
      polymer transport mechanisms. These mechanisms thus contribute directly to the
      shape of the axon by supplying it with essential architectural elements. The
      shape of the axon is further modulated by dynamic processes that alter
      cytoskeletal structure locally along its length. These dynamic processes include
      the assembly/disassembly mechanisms which influence polymer length and possibly
      number locally along the axon by subunit exchange between the monomer and polymer
      pools. In addition, the polymer transport mechanisms themselves are subject to
      modulation along the axon, as demonstrated by the observation that transport rate
      of MTs varies along the length of individual axons (Reinsch et al., 1991). Such
      local variations can, in and of themselves, change the number of MTs along the
      axon, and thereby focally affect axon shape. Thus, the dynamic processes of
      polymer transport and local assembly act cooperatively to shape the MT array of
      the axon, and thereby contribute directly to the elaboration of axonal
      morphology.

PMID- 7800834
TI  - Initial tract formation in the vertebrate brain.

PMID- 7800835
TI  - Dynamic mechanisms of neuronal outgrowth.

PMID- 7800836
TI  - Clinical manifestations and diagnostic imaging in transplant patients.

PMID- 7800837
TI  - Clinical problems in organ transplantation.

PMID- 7800838
TI  - Clinical problems of the transplanted kidney.

PMID- 7800839
TI  - Combined diagnostic imaging of the transplanted kidney.

PMID- 7800840
TI  - Postoperative clinical problems in the liver transplant patient.

PMID- 7800841
TI  - Pulmonary complications following orthotopic liver transplant: radiologic
      patterns and epidemiologic considerations in 100 cases.

PMID- 7800842
TI  - Abdominal complications and monitoring of liver transplants.

PMID- 7800843
TI  - Nuclear medicine and orthotopic liver transplant.

PMID- 7800844
TI  - Clinical problems in pediatric heart and heart-lung transplantation. Transplant
      Team.

PMID- 7800845
TI  - Diagnostic imaging in heart and heart-lung transplantation.

PMID- 7800846
TI  - Magnetic resonance imaging of single lung transplantation.

PMID- 7800847
TI  - The corrected primary structure of chicken (avian) pancreatic polypeptide.
AB  - Chicken (avian) pancreatic polypeptide was the first member of the pancreatic
      polypeptide (PP)/neuropeptide Y (NPY) superfamily to be discovered and
      structurally-characterised. In this 36 amino acid residue, C-terminally amidated
      peptide, residues 22 and 23 were identified as Asp and Asn, respectively.
      However, sequencing of chicken PP using modem automated gas-phase sequencing
      technology has revealed that the original primary structure is incorrect in that
      residue 22 is Asn and that residue 23 is Asp. After digestion of chicken PP with
      endoproteinase Asp-N, fragments of chicken PP corresponding in molecular mass to
      residues 16-22 and 23-36, were unequivocally identified. The corrected primary
      structure of chicken PP is therefore: Gly-Pro-Ser-Gln-Pro-Thr-Tyr-Pro-Gly-Asp-Asp
      Ala-Pro-Val-Glu-Asp-Leu-Ile-Arg- Phe-Tyr-Asn-Asp-Leu-Gln-Gln-Tyr-Leu-Asn-Val-Val
      Thr-Arg-His-Arg-Tyr-NH2.

PMID- 7800848
TI  - Cholecystokinin inhibits gastric emptying and contracts the pyloric sphincter in
      rats by interacting with low affinity CCK receptor sites.
AB  - The aim of these experiments was to characterize the receptor affinity state
      through which CCK produces pyloric contraction and inhibits gastric emptying in
      the rat using the novel CCK heptapeptide analog CCK-JMV-180. CCK-JMV-180 has been
      demonstrated to act as a functional agonist at high affinity pancreatic CCKA
      receptors but as a functional antagonist at CCKA low affinity receptors. CCK-8
      (1, 3.2 and 10 nM) induced dose dependent tension increases in isolated pyloric
      segments. CCK-JMV-180 (3.2 microM) or vehicle failed to mimic this action when
      administered alone but blocked the ability of CCK-8 (3.2 nM) to induce tension
      increases. CCK-8 (2 micrograms/kg) also inhibited the gastric emptying of
      physiological saline. CCK-JMV-180 (320 and 1000 micrograms/kg) failed to inhibit
      emptying when administered alone but dose dependently antagonized CCK induced
      inhibition of gastric emptying. Thus, in both preparations CCK-JMV-180 acted as a
      functional CCK antagonist. This profile is consistent with the interpretation
      that the actions of CCK in pyloric contraction and the inhibition of gastric
      emptying are mediated through CCK's interactions with receptors functionally
      similar to pancreatic low affinity sites.

PMID- 7800849
TI  - Pharmacological analysis of receptors for bombesin-related peptides on guinea pig
      gallbladder smooth muscle.
AB  - The aim of this study was to characterize the receptor(s) for bombesin (BN) and
      its homologues (gastrin releasing peptide, GRP; neuromedin B, NMB; neuromedin C,
      NMC) in guinea pig gallbladder muscle strips. Dose-dependent contractions were
      induced by all peptides tested (potency: BN = GRP > NMC > NMB, but with similar
      efficacy: BN = GRP = NMC = NMB). The contractions were resistant to tetrodotoxin,
      atropine, phentolamine, and propranolol. BN tachyphylaxis (1 microM) abolished
      subsequent contractile responses to BN, GRP and NMC; and partially antagonized
      the response to NMB (66 +/- 7% inhibition). NMB tachyphylaxis (10 microM)
      markedly inhibited subsequent contractile responses to NMB (78 +/- 5%); and
      partially antagonized the contractile response to BN (36 +/- 4%), GRP (31 +/-
      12%) and NMC (22 +/- 2%). At 1 microM, both [D-Phe6, Des-Met14]-BN(6-14)
      ethylamide and ICI 216, 140, two BN receptor antagonists, reduced the contractile
      actions of BN (82 +/- 4% and 59 +/-8% inhibition, respectively), GRP (75 +/- 11%
      and 45 +/- 5%), and NMC (73 +/- 9% and 51 +/- 6%) while having no marked effect
      on NMB contractions. Our pharmacological approaches (receptor tachyphylaxis and
      differential antagonism) provide support for two types of receptors for BN-like
      peptides on guinea pig gallbladder smooth muscle: a GRP-preferring receptor and a
      NMB-preferring receptor.

PMID- 7800850
TI  - Neuroendocrine regulation of growth hormone secretion in sheep. VII. Effects of
      GABA.
AB  - The effects of intravenous (i.v.) or intracerebroventricular (i.c.v.)
      administration of gamma aminobutyric acid (GABA) on plasma growth hormone (GH)
      concentrations have been examined in sheep. Intravenous administration of GABA
      resulted in a rapid, significant (P < 0.001) increase in plasma GH.
      Administration of 10 mg of GABA i.c.v. produced a significant (P < 0.001)
      increase in GH release. By contrast, 100 mg given i.c.v. was inhibitory and
      resulted in a decrease (P < 0.05) in plasma GH levels. Concurrent administration
      of somatostatin (0.5 microgram/min i.v. over 1 h) did not alter the plasma GH
      response to 10 mg GABA given i.c.v. These data are consistent with the concept of
      dual sites of action for GABA in regulating GH release in sheep, but the exact
      mechanism through which this effect is mediated remains unclear.

PMID- 7800851
TI  - In vitro steroidogenic effects of neuropeptide Y (NPY1-36), Y1 and Y2 receptor
      agonists (Leu31-Pro34 NPY, NPY18-36) and peptide YY (PYY) on rat adrenal
      capsule/zona glomerulosa.
AB  - The effects of neuropeptide Y (NPY1-36), of two analogs (Leu31-Pro34 NPY and
      NPY18-36) and of Peptide YY (PYY) on aldosterone and corticosterone secretions by
      freshly isolated rat adrenal capsule/zona glomerulosa preparations were
      investigated in vitro. NPY-related peptides (NPY1-36, Leu31-Pro34 NPY, NPY18-36),
      but not PYY, induced a dose-dependent release of aldosterone at concentrations
      ranging from 10(-8) to 10(-6) M. All the investigated peptides failed to
      significantly affect corticosterone secretion in concentrations ranging from 10(
      10) to 10(-6) M (NPY1-36, NPY18-36), 10(-11) to 10(-6) M (Leu31-Pro34 NPY) or 10(
      9) to 10(-6) M (PYY). Aldosterone secretion by this preparation of isolated
      adrenal capsule/zona glomerulosa was also significantly stimulated by high
      potassium levels (55 mEq) or by angiotensin II (AII) in concentrations ranging
      from 10(-8) to 10(-6) M. Moreover, NPY and Y1 or Y2 receptor agonists were
      positive aldosterone releasing agents as potent as AII. The present data support
      the existence of: (1) NPY binding sites of the Y3-like subtype, on rat adrenal
      capsule/zona glomerulosa. (2) A stimulatory effect of NPY on aldosterone
      production. So that the NPYergic innervation of the rat adrenal capsule/zona
      glomerulosa could be implicated in the multifactorial control of aldosterone
      production.

PMID- 7800852
TI  - Production and secretion of chromogranin A and pancreastatin by the human
      pancreatic carcinoma cell line QGP-1N on stimulation with carbachol.
AB  - Chromogranin A (CGA) is thought to be a precursor of pancreastatin (PST).
      Carbachol (Cch) stimulated the secretion of CGA and PST from QGP-1N cells derived
      from a human pancreatic islet cell tumor. Atropine inhibited the secretion of
      both. Sodium fluoride, phorbol ester, and calcium ionophore also stimulated the
      secretion of both. Cch (10(-5) M) stimulated inositol 1,4,5-trisphosphate
      production in QGP-1N cells. Stimulation with Cch increased the total amount of
      PST in the cells and the medium 1.7-fold and decreased the amount of CGA in the
      cells and medium. QGP-1N cells were labelled with [35S]methionine, and then CGA
      and PST in the cells and medium were immunoprecipitated with specific antisera,
      and separated by electrophoresis in polyacrylamide gel. Stimulation with Cch
      resulted in an increase in the intensity of PST-immunoreactive bands and a
      decrease in those of CGA-immunoreactive bands. Cch did not increase the cellular
      level of CGA messenger RNA. These results suggested that (1) the secretion of CGA
      and PST from QGP-1N cells is regulated mainly through muscarinic receptors
      coupled with activation of polyphosphoinositide breakdown by a G protein, with
      intracellular calcium ion and protein kinase C playing a role in the stimulus
      secretion coupling and that (2) Cch may induce the secretion of PST and CGA and
      processing from CGA to PST.

PMID- 7800853
TI  - Vasoactive intestinal peptide stimulates a cAMP-mediated Cl- current in avian
      salt gland cells.
AB  - VIP plays an integral role in both protein and fluid secretion in many exocrine
      glands. By employing the perforated patch-clamp whole-cell recording technique we
      investigated the effects of VIP on membrane potential and transmembrane currents
      in avian exocrine salt gland cells. Prior to application of VIP, salt gland cells
      had a resting membrane potential close to -45 mV. When challenged with VIP (1-100
      nM) a sustained depolarization to ECl- was induced which was mimicked by the
      application of cell-permeable cAMP analogues or forskolin (1 microM). By
      employing the voltage-clamp recording configuration a sustained increase in
      current was observed with a reversal potential which approximated ECl-. Ionic
      substitution experiments confirmed that the current was a Cl- conductance which
      was inhibited by the Cl- channel blockers flufenamic acid and niflumic acid and
      by the inhibitory cAMP isomer, adenosine-3',5'-cyclic monophosphothioate, Rp
      isomer. Based on this, and the fact that the kinetic properties of the Cl-
      current activated by VIP are similar to those activated by cAMP, we propose that
      VIP-receptor interaction results in the activation of a cAMP-dependent Cl-
      current.

PMID- 7800854
TI  - Neuropeptide Y functions as a physiologic regulator of cephalic phase acid
      secretion.
AB  - Neuropeptide Y (NPY) has been established as a potent orexigenic peptide, and
      recent studies suggest that NPY stimulates cephalic phase secretion as well.
      However, it is not known whether NPY's effects are pharmacologic or physiologic.
      In order to determine the physiologic significance of NPY, we examined the
      effects of two putative NPY receptor antagonists, PYX-1 and PYX-2, on sham
      feeding and gastric acid secretion in dogs. Our results demonstrate that
      intracerebroventricular (i.c.v.) injection of PYX-1 and PYX-2 at 1000 pmol/kg
      doses significantly suppresses the gastric acid response to sham feeding in dogs.
      The volumes sham fed were not significantly altered with i.c.v. administration of
      the antagonists. Peripheral administration did not affect acid secretion nor sham
      feeding volumes. Our data suggest that central administration of the novel NPY
      antagonists, PYX-1 and PYX-2, results in significant suppression of acid
      secretion in dogs. This supports our hypothesis that NPY functions as a
      physiologic modulator of cephalic phase acid secretion.

PMID- 7800855
TI  - Culekinin depolarizing peptide: a mosquito leucokinin-like peptide that
      influences insect Malpighian tubule ion transport.
AB  - A peptide termed culekinin depolarizing peptide (CDP) was isolated from
      approximately 1.2 million mosquitos (94% Culex salinarius). The peptide was
      isolated on the basis of a rapid myotropic assay that utilized a hindgut
      preparation from Leucophaea maderae and a transepithelial voltage assay that used
      mosquito Malpighian tubules from Aedes aegypti. A 15% trifluoroacetic acid
      extraction from the mosquitos, two solid phase extraction steps, and six HPLC
      steps resulted in the isolation of 9.7 nmol of CDP. This value corresponds to
      approximately 8 fmol/mosquito. Edman degradation indicated the following sequence
      for CDP: Asn-Pro-Phe-His-Ser-Trp-Gly-NH2. The sequence was confirmed as the
      suspected C-terminal amide form of the peptide, since native and synthetic CDP
      had identical chemical and biological properties. CDP is a member of the
      leucokinin family of neuropeptides. The leucokinins have been found in three
      other insect species (Leucophaea maderae, Acheta domesticus and Locusta
      migratoria) where these peptides were isolated by their myotropic properties
      alone. CDP shares a C-terminal sequence homology (i.e., Phe-X-Ser-Trp-Gly-NH2)
      with the rest of the leucokinins. CDP corresponds to the strongest tubule
      depolarizing activity in the C. salinarius extract. These findings agree with
      previous structure-activity studies that suggest that mosquitos would contain a
      leucokinin-like factor that had Phe-His-Ser-Trp-Gly-NH2 as the C-terminal
      pentapeptide. This is the first leucokinin isolated from blood feeding or
      holometabolous insects.

PMID- 7800856
TI  - BON cells display the intestinal pattern of neurotensin/neuromedin N precursor
      processing.
AB  - Antisera towards the bioactive peptides, neurotensin (NT, 13 residues) and
      neuromedin N (NMN, 6 residues), as well as towards three regions of their 147
      residue canine precursor were used to identify and to quantitate precursor
      derived peptides in extracts of human BON cells. This cell-line, which was
      obtained from a human pancreatic carcinoid tumor, constitutively expresses NT/NMN
      mRNA and secretes NT. Quantitation of seven precursor-derived peptides led us to
      conclude that BON cells display the intestinal pattern of NT/NMN precursor
      processing, which is primarily characterized by the production of a large
      molecular (125 amino acid) form of NMN. Four large molecular components,
      identified by immunochemical analyses and Western blotting, displayed physico
      chemical properties which, for the most part, were consistent with the structures
      predicted from the partially-known human mRNA sequence. However, as shown
      previously for these peptides in canine gut, the empirically determined M(r) and
      pI values were slightly higher than those predicted solely from the amino acid
      content, perhaps due to the presence of additional substituents. These results
      suggest that BON cells may provide a good in vitro model in which to study the
      regulation of intestinal NT/NMN precursor processing and the nature of the
      enzyme(s) involved.

PMID- 7800857
TI  - Down regulation of the angiotensin II receptor subtype AT2 in human myometrium
      during pregnancy.
AB  - Samples of human myometrium have been collected during pregnancy and from non
      pregnant women. Binding studies revealed the presence of a 50-fold higher density
      of angiotensin II AT2 receptor in the non-pregnant state than during gestation.
      Low levels of the AT1 receptor subtype (approx. 20 fmol/mg protein) were detected
      in both pregnant and non-pregnant myometrium. Outside pregnancy, the AT2 receptor
      accounted for greater than 95% of all angiotensin receptors, whereas during
      pregnancy the value dropped to about 40%. The down regulation of the human
      myometrial AT2 receptor during pregnancy may be related to the high hormonal
      content of the environment induced by gestation. The mechanism by which the AT2
      receptor is regulated appears to be different to that of the AT1 receptor.

PMID- 7800858
TI  - Use of 125I-[Y39]exendin-4 to characterize exendin receptors on dispersed
      pancreatic acini and gastric chief cells from guinea pig.
AB  - We synthesized and iodinated an exendin-4 analogue, [Y39]exendin-4 (700 Ci/mmol),
      for use as a radioligand to characterize exendin receptors on dispersed
      pancreatic acini and gastric chief cells from guinea pig. Binding of this
      bioactive radioligand was rapid, temperature-dependent and specific (not
      inhibited by other pancreatic or gastric secretagogues). Measurement of the
      ability of exendin-4 to inhibit the binding of 125I-[Y39]exendin-4 indicated the
      presence of two classes of receptors. Pancreatic acini had 12.5.10(10) binding
      sites/mg acinar protein of which 6% were high affinity (Kd = 0.5 nM) and 94% were
      low affinity (Kd = 0.1 microM). Chief cells had 3370 binding sites/cell of which
      9% were high affinity (Kd = 0.3 nM) and 91% were low affinity (Kd = 0.2 microM).
      Washing with 0.2 M acetic acid (pH 2.5), 0.2 M glycine (pH 10.5), or trypsin (100
      micrograms/ml) after 30 min incubation at 37 degrees C, indicated that 63 and 49%
      of radioligand was internalized in acini and chief cells, respectively. Truncated
      glucagon-like peptide-1 (tGLP-1), a mammalian peptide sharing 53% homology with
      exendin-4, inhibited radioligand binding at the same concentrations that altered
      secretion from acini and chief cells. Glucagon, GLP-1 and GLP-2 inhibited 125I
      [Y39]exendin-4 binding only at concentrations > or = 100 nM. Exendin(9-39)NH2, a
      specific exendin-receptor antagonist, potently inhibited 125I-[Y39] exendin-4
      binding (IC50 = 6.1 and 3.5 nM in acini and chief cells, respectively). In
      pancreatic acini and gastric chief cells from guinea pig, exendin-3, exendin-4
      and tGLP-1 increase cellular cAMP and modulate enzyme secretion by interacting
      with high-affinity exendin receptors. 125I-[Y39] exendin-4 is a useful
      radioligand for studying exendin receptors.

PMID- 7800859
TI  - Growth-regulatory effect of gastrin on human colon cancer cell lines is
      determined by protein kinase a isoform content.
AB  - Cell growth is regulated by various peptide growth factors through receptor
      linked multiple intracellular signal-transduction pathways, such as the cyclic
      adenosine monophosphate (cAMP) pathway. cAMP activates cAMP-dependent protein
      kinase A (PKA) either to stimulate or inhibit cell growth. The effect on growth
      is determined by the presence of two isoforms of the regulatory (R) subunit of
      PKA; activation of RI alpha-type PKA leads to stimulation of growth, activation
      of RII beta-type inhibits cell growth. We determined whether the effect of
      gastrin on the growth of human colon cancer cells is determined by cell-specific
      content of PKA. We utilized two human colon cancer cell lines: LoVo, growth of
      which is stimulated by gastrin, and HCT116, growth of which is inhibited by
      gastrin. Activation of both types of PKA with 8-Br-cAMP mimicked the regulation
      of growth by gastrin; preferential activation of RII beta-type PKA with 8-Cl-cAMP
      inhibited growth of both cell lines. LoVo cells possess the predominantly RI
      alpha isoform of PKA at the mRNA and protein level; HCT116 cells possess
      predominantly the RII beta-type PKA. The cAMP-mediated regulation of growth
      (either stimulatory or inhibitory) by gastrin on these human colon cancer cells
      was determined by the predominant isoform of PKA.

PMID- 7800860
TI  - Receptor-mediated internalization of angiotensin II in bovine adrenal medullary
      chromaffin cells in primary culture.
AB  - Binding and internalization of angiotensin II (AII) were studied on bovine
      adrenal medullary cells in primary culture. Binding of [125I]AII was reversible,
      saturable, specific and showed high affinity. AII was found to be internalized by
      bovine adrenal medullary cells. Monensin increased whereas phenylarsine oxide
      (PhAsO) decreased the internalization. Excess of unlabelled AII or saralasin
      could block the internalization, indicating a receptor mediated internalization
      process. The kinetic analysis indicated that, during the first 4 min, about 25%
      of the membrane bound ligand was internalized per min and the recycling of
      internalized ligand and receptor initiated around 4 min.

PMID- 7800861
TI  - Propagation of uncertainty in risk assessments: the need to distinguish between
      uncertainty due to lack of knowledge and uncertainty due to variability.
AB  - In quantitative uncertainty analysis, it is essential to define rigorously the
      endpoint or target of the assessment. Two distinctly different approaches using
      Monte Carlo methods are discussed: (1) the end point is a fixed but unknown value
      (e.g., the maximally exposed individual, the average individual, or a specific
      individual) or (2) the end point is an unknown distribution of values (e.g., the
      variability of exposures among unspecified individuals in the population). In the
      first case, values are sampled at random from distributions representing various
      "degrees of belief" about the unknown "fixed" values of the parameters to produce
      a distribution of model results. The distribution of model results represents a
      subjective confidence statement about the true but unknown assessment end point.
      The important input parameters are those that contribute most to the spread in
      the distribution of the model results. In the second case, Monte Carlo
      calculations are performed in two dimensions producing numerous alternative
      representations of the true but unknown distribution. These alternative
      distributions permit subject confidence statements to be made from two
      perspectives: (1) for the individual exposure occurring at a specified fractile
      of the distribution or (2) for the fractile of the distribution associated with a
      specified level of individual exposure. The relative importance of input
      parameters will depend on the fractile or exposure level of interest. The
      quantification of uncertainty for the simulation of a true but unknown
      distribution of values represents the state-of-the-art in assessment modeling.

PMID- 7800862
TI  - Designing risk communications: completing and correcting mental models of
      hazardous processes, Part I.
AB  - Many risk communications are intended to help the lay public make complex
      decisions about risk. To guide risk communicators with this objective, a mental
      models approach to the design and characterization of risk communications is
      proposed. Building on text comprehension and mental models research, this
      approach offers an integrated set of methods to help the risk communication
      designer choose and analyze risk communication content, structure, and
      organization. An applied example shows that two radon brochures designed with
      this approach present roughly the same expert facts as a radon brochure widely
      distributed by the U.S. EPA but meet higher standards on other content,
      structure, and organization criteria.

PMID- 7800863
TI  - Evaluating risk communications: completing and correcting mental models of
      hazardous processes, Part II.
AB  - We propose a decision-analytic framework, called the mental models approach, for
      evaluating the impact of risk communications. It employs multiple evaluation
      methods, including think-aloud protocol analysis, problem solving, and a true
      false test that allows respondents to express uncertainty about their answers.
      The approach is illustrated in empirical comparisons of three brochures about
      indoor radon.

PMID- 7800864
TI  - Public perceptions of the potential hazards associated with food production and
      food consumption: an empirical study.
AB  - Although public perceptions of food-related hazards receive much media comment
      and debate, the research literature on such perceptions is sparse and piecemeal.
      In the reported study, 216 people completed a questionnaire relating to their
      perceptions of the "risk characteristics" of potential hazards associated with
      various aspects of food production and food consumption. Responses were examined
      via principal-components analysis to obtain a structural representation of risk
      perception of the kind provided by Fischhoff, Slovic, and their colleagues in
      their seminal psychometric work. A three-component solution accounting for 87% of
      the variance was obtained, with the dimensions labeled as "severity," "unknown,"
      and "number of people exposed." The findings also yielded information pointing to
      evidence of the phenomenon of unrealistic optimism. We conclude that our findings
      offer a useful base upon which further in-depth research integrating different
      perspectives on risk perception with respect to food-related hazards may be
      developed.

PMID- 7800865
TI  - Use of biological markers in risk assessment.
AB  - Measurements of intermediate end points in the carcinogenic process may reduce
      uncertainty in human risk assessment from bioassay data, by identifying sources
      of interspecies variation and dose nonlinearity. This paper describes desirable
      properties of such markers: persistence, predictive power, temporal relevance,
      and consistency across dose rate and species. We illustrate these properties by
      evaluating markers for squamous cell nasal carcinoma in rodents exposed to
      formaldehyde. We also discuss design issues for bioassays that evaluate markers
      and tumors simultaneously at necropsy.

PMID- 7800866
TI  - Perception of risks from electromagnetic fields: a psychometric evaluation of a
      risk-communication approach.
AB  - Potential health risks from exposure to power-frequency electromagnetic fields
      (EMF) have become an issue of significant public concern. This study evaluates a
      brochure designed to communicate EMF health risks from a scientific perspective.
      The study utilized a pretest-posttest design in which respondents judged various
      sources of EMF (and other) health and safety risks, both before reading the
      brochure and after. Respondents assessed risks on dimensions similar to those
      utilized in previous studies of risk perception. In addition, detailed ratings
      were made that probed respondents' beliefs about the possible causal effects of
      EMF exposure. The findings suggest that naive beliefs about the potential of EMF
      exposure to cause harm were highly influenced by specific content elements of the
      brochure. The implications for using risk-communication approaches based on
      communicating scientific uncertainty are discussed.

PMID- 7800867
TI  - Database requirements for epidemiological estimates of radiation risks in
      continuously exposed populations.
AB  - Using the revised risk coefficients recommended by the 1990 report of the
      International Commission of Radiological Protection (ICRP), computations have
      been made on the minimum databases required for detecting radiogenic cancer
      excesses from epidemiological surveys of populations exposed to low level
      radiations. The computations have been made separately for Indian and Western
      populations using their representative demographic data. The western database
      requirements are generally found to be about half the Indian requirement. For the
      exposures in high background radiation areas at the rate of say 5 mSv/y, the
      minimum required database is 121,500 person years, in the Indian case. Similarly,
      for Indian occupational workers exposed at the rate of say, 10 mSv/y, it is
      required to observe 30,000 persons for the first 40 years or 3600 persons over
      their entire lifetime for obtaining statistically significant results.

PMID- 7800868
TI  - Point estimates of cancer risk at low doses.
AB  - There has been considerable discussion regarding the conservativeness of low-dose
      cancer risk estimates based upon linear extrapolation from upper confidence
      limits. Various groups have expressed a need for best (point) estimates of cancer
      risk in order to improve risk/benefit decisions. Point estimates of carcinogenic
      potency obtained from maximum likelihood estimates of low-dose slope may be
      highly unstable, being sensitive both to the choice of the dose-response model
      and possibly to minimal perturbations of the data. For carcinogens that augment
      background carcinogenic processes and/or for mutagenic carcinogens, at low doses
      the tumor incidence versus target tissue dose is expected to be linear.
      Pharmacokinetic data may be needed to identify and adjust for exposure-dose
      nonlinearities. Based on the assumption that the dose response is linear over low
      doses, a stable point estimate for low-dose cancer risk is proposed. Since
      various models give similar estimates of risk down to levels of 1%, a stable
      estimate of the low-dose cancer slope is provided by s = 0.01/ED01, where ED01 is
      the dose corresponding to an excess cancer risk of 1%. Thus, low-dose estimates
      of cancer risk are obtained by, risk = s x dose. The proposed procedure is
      similar to one which has been utilized in the past by the Center for Food Safety
      and Applied Nutrition, Food and Drug Administration. The upper confidence limit,
      s., corresponding to this point estimate of low-dose slope is similar to the
      upper limit, q1., obtained from the generalized multistage model. The advantage
      of the proposed procedure is that s provides stable estimates of low-dose
      carcinogenic potency, which are not unduly influenced by small perturbations of
      the tumor incidence rates, unlike q1.

PMID- 7800869
TI  - [Seroprevalence of hepatitis B virus markers in pregnant women attending a public
      hospital in Navarra].
AB  - OBJECTIVE: To design efficient massive immunization programs for newborns it is
      essential to know the prevalence of HBV infection in pregnant women. As a
      contribution to this knowledge the prevalence of HBV markers was studied in
      pregnant women attended at a public hospital in Navarra. An assessment was also
      made of the relationship between prevalence of HBV markers and other
      epidemiological factors. METHODS: The gestational history was reviewed of 2,499
      pregnant women aged 14-45 years attended at the hospital during 1991. The
      following factors were investigated: age, profession, job, and educational level
      of the woman and her partner, residence, Health Area, risk factors and
      serological markers (HbsAG, anti-HBs, anti-HBc, and, when appropriate, HBeAg/anti
      Hbe. RESULTS: The screening rate of HBsAg in the group of pregnant women was 70%;
      the prevalence of positive HbsAg was 0.70%. The respective prevalence rates of
      anti-HBs, anti-HBc, and AMP were 6%, 7.5% and 8.6%. The type of residence, social
      class and risk exposure had influence on the prevalence of positive markers.
      CONCLUSIONS: The 70% of screening rate in the group of pregnant women is still
      far from reaching the goal of 95% intended in the Plan de Salud Infantil in
      Navarra for 1993. A prevalence of 0.70 for positive HBsAg was observed. No
      geographical differences were observed in the distribution of HBV markers, but
      its prevalence was influenced by the type of residence, social class and risk
      exposure. A discussion follows whether a massive immunization program form
      newborns in Navarra is warranted.

PMID- 7800870
TI  - [Seroprevalence of delta virus and hepatitis C virus in patients with chronic
      infection with hepatitis B virus].
AB  - OBJECTIVE: To study the prevalence of hepatitis delta and hepatitis C viruses
      (HDV and HCV) in patients infected with hepatitis B virus (HBV) with and without
      risk behaviors for the infection by these viruses and by the human
      immunodeficiency virus (HIV). MATERIALS AND METHODS: Clinical and serological
      study (January 1990-December 1992) at Medicine Service at Galdacano Hospital of
      109 patients with positive hepatitis B surface antigen and without clinical or
      serological evidence of acute hepatitis, 60 without risk behaviors for the
      infection, 45 parenteral drug abusers (PDA) and 4 homosexual males. RESULTS:
      Chronic HDV infection was observed in 60% of PDA and more frequently among HIV
      positive patients (p < 0.05). In six of these patients the serological
      determination of HDV-Ag was positive. Chronic HDV and HCV infection rates in
      patients without risk behaviors were 1.6% and 16%, respectively. Eighty-eight
      percent of PDA had anti-HCV; no differences were observed between HIV-positive
      and HIV-negative patients (p = 0.64). CONCLUSIONS: HDV was particularly
      associated with parenteral drug abuse, with a similar prevalence to other surveys
      conducted in Spain. The higher frequency of HDV and HDV-Ag among HIV-positive
      patients could indicate a greater susceptibility to HDV in clinical conditions
      associated with immunosuppression. HCV infection occurs at early stages and is
      common among PDA infected with HBV, with no apparent association with patient's
      age, years of drug abuse or HIV infection.

PMID- 7800871
TI  - [Measurement of vibratory threshold in the diagnosis of diabetic neuropathy].
AB  - The usefulness of the quantitative measurement of vibration perception threshold
      (VPT) was assessed by a biothesiometer in the diagnosis of peripheral neuropathy
      in 36 patients with type I diabetes mellitus. The study included: a) clinical
      assessment (history and neurological examination); b) measurement of VPT at right
      metatarsus, right pretibial area and right metacarpus; c) electromiographical
      study (right peroneal, posterior tibial, right sural, right medial plantar); d)
      assessment of the autonomous nervous system (sympathetic and parasympathetic
      indexes); e) metabolic assessment (HbA1c at study and mean HbA1c in the previous
      year). The prevalence of peripheral neuropathy was 38%. VPT at metatarsal region
      in diabetic patients was higher than in controls (p < 0.05) and a positive
      correlation with evolution time of disease at metatarsal region (p < 0.05) and
      tibia (p < 0.05) was observed. Clinical symptoms and changes at examination
      correlated with VPT at metatarsus (p < 0.05) and tibia (p < 0.05). No
      relationship was observed between VPT and metabolic control. In conclusion,
      vibration threshold increases with evolution time in diabetes, but it was not
      influenced by metabolic control. Its measurement by a simple method, such as
      biothesiometer, could be useful in diagnosing peripheral neuropathy in clinically
      asymptomatic patients.

PMID- 7800872
TI  - [Variation in blood pressure values in a pediatric population assigned to a
      primary care team by applying a correction factor according to brachial
      perimeter].
AB  - OBJECTIVE: To quantitative changes in blood pressure values and in hypertension
      diagnosis after applying a correction factor (CF) according to brachial
      perimeter. MATERIALS AND METHODS: A sample of 164 male and female children, aged
      11-14 years from a population attended at our Health Institution was studied.
      Blood pressure and brachial perimeter at the right arm were determined in all
      children and the CF was applied according to brachial perimeter. RESULTS: Mean
      brachial perimeter was 23.8 cm, with a higher value in males (p < 0.05); a
      significant increase in blood pressure values was observed both for the overall
      sample and for both sexes taken separately; prevalence of hypertension increased
      significantly after correction of sample and for males, not for females.
      CONCLUSIONS: For an appropriate blood pressure measurement it is essential to
      correctly fit the cuff bladder size to the brachial perimeter; when it is not
      possible the CF should be applied.

PMID- 7800873
TI  - [Lymphoma of the ocular adnexa].
AB  - Ocular adnexa are rarely involved in lymphomas. Four cases are reported of
      lymphoma involving the ocular adnexa. In two cases a previous systemic
      involvement existed or simultaneous to the ocular involvement; another patient
      had systemically a different histological pattern to that observed in the ocular
      region, and the fourth patient only had ocular region, and the fourth patient
      only had ocular symptoms; we therefore recorded two cases of primary ocular
      lymphoma. The lymphoma was located at the orbit in two cases and at the
      conjunctiva in the other two cases; the condition was bilateral in three cases.
      The most common symptom was exophtalmus; other major symptoms were diplopia and
      disturbances in ocular motility. The histological examination revealed three low
      grade lymphomas and one case of intermediate grade. Management of patients
      included radiotherapy and different chemotherapeutic regimens with a good
      response in all cases. A higher ocular relapse rate was observed in those
      patients with systemic involvement; in one primary case the condition resolved
      spontaneously. A review of the literature on clinical, diagnostic and therapeutic
      issues is made.

PMID- 7800874
TI  - [Pathological hyperprolactinemia].

PMID- 7800875
TI  - [Pneumopericardium: review of the literature].

PMID- 7800876
TI  - [The endocrine-metabolic response to stress].

PMID- 7800877
TI  - [Fulminant sepsis in a splenectomized patient. Waterhouse-Friderichsen syndrome
      due to pneumococcal sepsis].

PMID- 7800878
TI  - [Retinal involvement in cardiac transplant. Retinitis due to cytomegalovirus in a
      cardiac transplant recipient].

PMID- 7800879
TI  - [70 Year old male with rapid consciousness damage and respiratory alkalosis].

PMID- 7800880
TI  - [Prostatic adenocarcinoma and increase in creatine kinase levels: some comments
      on its significance].

PMID- 7800881
TI  - [Scleroderma as a marker of poor control in diabetes mellitus].

PMID- 7800882
TI  - [Obstructive uropathy and Churg-Strauss disease].

PMID- 7800883
TI  - [Burning pain at the 3rd intermetatarsal space: report of a case of Morton
      neurinoma].

PMID- 7800884
TI  - Preparacion toxoide a partir de la fraccion hemorragica del veneno de Bothrops
      asper (serpiente de America Central y del Sur) (Toxoid preparation from
      hemorrhagic fraction of the venom from Bothrops asper (snake from Central and
      South America).
AB  - A technique is described for preparing a toxoid from the hemorrhagic fraction of
      the Bothrops asper venom. This method conserves a high degree of immunogenicity
      although it eliminates lethal effects. None of the animals vaccinated with the
      toxoid from this fraction had hemorrhagic lesions after they were injected the
      venom from the hemorrhagic fraction.

PMID- 7800885
TI  - [Identification and isolation of common antigens of Fasciola hepatica].
AB  - Four antigenic polypeptides present in excretion-secretion antigens which were
      common to Fasciola hepatica somatic and tegumentary antigens, were identified by
      Western blotting and purified by affinity chromatography. Monoclonal antibody
      ES78 was used to that purpose. Molecular weights calculated for these
      polypeptides ranged from 37 to 13 kd; they proved to be highly reactive with sera
      from animals experimentally infected by Fasciola hepatica in periods as early as
      the second week of infection, with maximal values in weeks 6 and 10.

PMID- 7800886
TI  - [Assessment of the antibody response in patients with giardiasis].
AB  - Of 104 patients under study for giardiasis-like clinica symptoms, 101 were
      parasitologically positive. The presence of antibodies was shown in 99 of them,
      which means 96% sensitivity and 90% specificity in the indirect
      immunofluorescence technic. Antibody response was significantly higher (p < 0.01)
      in those patients with no history of the disease. A significant fall (p < 0.01)
      was seen in antibody titres in all patients a month after the effective
      treatment, as well as well as persistent positive titres in those who were not
      cured.

PMID- 7800887
TI  - [Human leptospirosis behavior in Cuba].
AB  - A description is made of the antecedents of human leptospirosis in Cuba and the
      behavior of the disease from 1981. An analysis with regards lethality and
      incidence during the five-year period 1986-1990 was carried out; the most
      affected provinces, the months of highest occurrence, and the most hazardous
      occupations, are listed. The present situation of human leptospirosis in Cuba is
      described and recommendations are provided.

PMID- 7800888
TI  - [Trichuriasis in Cuba].
AB  - A representative sample of the Cuban population (11,364) is studied by using
      Willis and direct coproparasitological techniques. It was found that Trichuris
      trichiura is the most prevailing intestinal parasite (17.8%). A higher frequency
      of this kind of geohelminthiasis in people living in Cuban rural zones is seen. A
      prevalence peak is found in ages from 6 to 9 years, and a higher association of
      parasitism was found in those with worst hygienic and sanitary conditions.

PMID- 7800889
TI  - [Identification of gram negative, facultative anaerobic, oxidase positive
      bacilli].
AB  - We identified 100 strains of Gram-negative, oxidase-positive bacilli, facultative
      anaerobes, isolated from different human pathological products by conventional
      biochemical methods. From the total number of strains studied, 1 corresponded to
      genus Vibrio, 66 to genus Aeromonas, and 33 to genus Plesiomonas. It is of the
      utmost importance to conduct surveillance studies of these microorganisms in
      order to investigate their circulation in Cuba.

PMID- 7800890
TI  - [Stages of the historic evolution of the antituberculosis campaign in Cuba].
AB  - A brief account is provided on the main characteristics of the stages in the
      historical evolution of struggle against tuberculosis in Cuba. The foundations
      and the steps taken in tuberculosis control are noted. A synthesis of therapeutic
      schemes used in the last 20 years is provided and the tendency of notification of
      new cases in 1979-1988 is discussed. During that ten-year period there was a
      38.8% reduction.

PMID- 7800891
TI  - [Cryptosporidium sp. infection in Cuban individuals infected by HIV].
AB  - A study was conducted on the presence of Cryptosporidium sp in 47 Cuban adult
      patients infected by HIV in different infective stages in order to assess for the
      first time its prevalence in this group. The parasite was found in 18 patients
      (38.3%), of whom 18 (44.7%) were asymptomatic. The most frequent symptoms were
      aqueous diarrhea, fever, abdominal colics, asthemia and weight loss. Emphasis is
      placed on the frequently asymptomatic nature of these infections, which could be
      an important reservoir for nosocomial transmission of this disease among
      individuals with immunological disregulations.

PMID- 7800892
TI  - [International health monitoring. Special screening among foreign grant
      recipients at their arrival in Cuba].
AB  - A description in made about the methodology and outcome of screening conducted on
      foreing students arriving in Cuba from 1987-1990 to reside for several years.
      During that period, a total number of 13,025 foreing travellers coming from 36
      countries were controlled; of them, 1,100 were positive to some kind of
      infectious disease. The majority were positive to malaria (838), 220 cases were
      diagnosed as having epidemic hemorrhagic conjunctivitis and 58 were seropositive
      to HIV. All positive cases were controlled and treated by the Department of
      Medical Services of the Institute of Tropical Medicine "Pedro Kouri".

PMID- 7800893
TI  - [The Scientific Pole].

PMID- 7800894
TI  - [Standardization of an inhibition ELISA technique for the serologic diagnosis of
      coxsackie virus group B infections].
AB  - An inhibition ELISA technic to detect antibodies aimed at Coxsackie B viruses was
      standardized. The method was type-specific since it could detect antibodies to 4
      Coxsackie B serotypes (it wasn't tried on serotypes B2 and B4 because the strains
      were not available). The comparison with the neutralization technic showed 85%
      coincidence, 91% sensitivity and 82% specificity. All the reactives used in the
      assay were produced in our laboratory.

PMID- 7800895
TI  - [Evaluation of the counterimmunoelectrophoresis technique for the serologic
      diagnosis of leptospirosis].
AB  - The counterimmunoelectrophoresis (CIE) technic was assessed for leptospirosis
      serological diagnosis by using an antigenic preparation from Leptospira biflexa
      Patoc I strain. It was showed that the CIE technic had 82% sensitivity and 100%
      specificity. The antigen used showed a gender-specific reactivity on detecting
      antibodies in patients infected by different leptospirosis serogroups by
      microagglutination test. Antigen stability for CIE technic was 6 months without
      loss of titre.

PMID- 7800896
TI  - [Influenza and other acute respiratory infections. Republic of Cuba, 1989].
AB  - Information is provided on the epidemiological situation of influenza and other
      acute respiratory tract diseases in Cuba during 1989. General mortality rate was
      25.4 per 105 inhabitants. Global morbidity rate was 373.9 per 1,000 inhabitants.
      The highest morbidity rate reported corresponded to children 5-14 years old and
      under 1 year of age. Serologically, the viral agent proportionally most
      identified was influenza virus type A (H3N2).

PMID- 7800897
TI  - [Sampling procedure for a survey of an interventional study on acute respiratory
      infections].
AB  - A description is made of the methodology used for obtaining a sample made up of
      500 children under 5 years and 500 adults 65 year old and more, in order to carry
      out an intervention study on acute respiratory tract infections in an urban zone
      in Havana City and in a rural zone in Matanzas province, where different
      intervention stops will be taken with regards sanitary education about management
      of acute respiratory tract infections for the population and training for primary
      care medical personnel. We show the way the selected sample fits was planned with
      a very homogeneous distribution in the 8 areas under study, which allows for
      great reliability in the results.

PMID- 7800898
TI  - [Several aspects of the bacteriology of Mycobacterium leprae].

PMID- 7800899
TI  - [The pharmacological prevention of atrial fibrillation after cardioversion].

PMID- 7800900
TI  - [The use of angiotensin-converting enzyme inhibitors in anterior infarct without
      congestive symptoms. The arguments contra].

PMID- 7800901
TI  - [The use of angiotensin-converting enzyme inhibitors in anterior infarct without
      congestive symptoms. The arguments pro].

PMID- 7800902
TI  - [The mechanism producing nausea during ventriculography performed with ioxaglate:
      the implications of a randomized study].
AB  - INTRODUCTION: The mechanism of ioxaglate-induced nausea has not been fully
      elucidated. Recent studies have demonstrated that serotonin is one of the
      principal neurotransmitters of emesis in humans. On the other hand, the greater
      capacity of ioxaglate to stimulate vomiting has been ascribed to its great
      ability to inhibit cholinesterase. METHODS: To determine if oral metoclopramide
      (a serotonin receptor-blocker) is effective in the prophylaxis of ioxaglate
      induced nausea during left ventriculography, 637 of 711 consecutive eligible
      patients were included in a prospective study. Patients were randomized to
      receive, 60-90 minutes before the procedure, either diazepam 10 mg p.o. (control
      group [n = 315]) or diazepam 10 mg p.o. plus metoclopramide 10 mg p.o.
      (metoclopramide group [n = 322]). RESULTS: The two randomized groups were similar
      in relation to baseline clinical and hemodynamic characteristics. Nausea was
      documented in 103 patients (16.1%) with similar incidence in the two groups
      (control group: 16.8%, metoclopramide group: 15.5%; p = NS). Nausea duration was
      also similar (56 +/- 63 s vs 52 +/- 63 s; p = NS). When patients with and without
      nausea were compared, the following variables showed a significant difference
      between the two groups: male gender (86% vs 76%; p < 0.05), age (53 +/- 10 yrs vs
      56 +/- 9 yrs; p < 0.05) and body surface area (1.84 +/- 0.2 m2 vs 1.78 +/- 0.1
      m2; p < 0.01). Stepwise multiple regression analysis identified low age (p =
      0.02) and male gender (p = 0.06) as independent predictors of nausea. The
      incidence of nausea was 24% in males < or = 45 yrs vs 9% in females > 45 yrs (p <
      0.05). CONCLUSIONS: Prophylaxis with oral metoclopramide did not reduce the
      incidence of ioxaglate-induced nausea during left ventriculography. This data do
      not support a role of serotonin in the production of nausea by ioxaglate. Low age
      an male gender are independent predictors of nausea apparition during left
      ventriculography. A cholinergic mechanism is probably involved in the capacity of
      ioxaglate to stimulate vomiting.

PMID- 7800903
TI  - [The usefulness of transesophageal echocardiography in general intensive care
      units].
AB  - BACKGROUND AND OBJECTIVES: It's well known the utility of transesophageal
      echocardiography in the evaluation of cardiological patients that are critically
      ill. However, there is less experience about this usefulness in non-cardiological
      critically ill patients. METHODS: To assess the utility and safety of the method
      we analyzed 51 correlative studies of patients admitted to our general Intensive
      Care Unit. Forty-seven patients (92%) were on mechanical ventilation and in 24
      patients (47%) continuous assessment of the hemodynamic variables were available.
      RESULTS: The most frequent diagnoses on admission were sepsis (23.5%) and shock
      status (17.6%). The indications were: suspicion of endocarditis (15 patients),
      hemodynamic instability (11 cases), cardiac source of embolus (10), suspicion of
      cardiac tamponade (4), suspicion of aortic dissection (4) and other causes in 7.
      The study confirmed the clinical suspicion in 31 cases (60.8%), excluded it in 15
      (29.4%) and established a new, non-suspected, diagnosis in 5 patients (9.8%).
      There were major diagnostic changes in 16 patients (31.6%) and minor changes in
      17 (33.3%) comparing the results of the transesophageal and transthoracic
      approaches. It was also assessed the influence of the result on the clinical
      management of the patient: in 32 cases (62.8%) there were a significant change in
      the treatment; in 5 patients (9.8%) cardiac surgery was prompted by
      echocardiography. Only in 3 patients hypertensive reactions and tachycardia were
      detected, without posterior consequences. CONCLUSIONS: Transesophageal
      echocardiography can be safely performed and has a definite role in the diagnosis
      (showing sometimes non-suspected abnormalities) and management of non
      cardiological critically ill patients.

PMID- 7800904
TI  - [A change in the prescription of thrombolytic treatment in elderly patients. The
      experience of the Hospital de Leon].
AB  - INTRODUCTION AND OBJECTIVES: Most deaths caused from AMI occur in elderly
      patients, and it is know that these patients way also benefit from the type
      treatment normally offered to younger patients. We proposed to analyse how our
      therapeutic strategy has evolved for patients of advanced age related to the
      admission in the CCU and the prescription of thrombolytic treatment. METHODS: In
      order to carry our investigation, we compared the clinical profile, the treatment
      and the results of patients over the age of 70 who were hospitalized in our
      Service with suspected AMI during last 3 years. A total number of 366 which were
      divided into two consecutive periods of 18 months; 176 patients from January'91
      to June'92 (Period I--former--) and 190 patients from July'92 to December'93
      (Period II--latter--). RESULTS: In both periods, nearly all patients with
      suspected AMI and < 48 hours of since symptoms began were hospitalized in the CCU
      irrespective of their age. In both periods, over 40% of the total number of
      patients admitted to CCU were > 70 years (I: 45.2% vs II: 42.6%). We observed
      that in the latter group a major part of patients had complicated AMI at the
      moment of admittance (I: 15.3% vs II: 24.2%; p < 0.05). This is probably related
      to a less favorable clinical profile. Despite this, a parallel increase in
      hospital death rate was not observed (I: 21% vs II: 17%; p: NS). Over time, the
      ratio of patients prescribed with thrombolysis > 70 was nearly doubled (I: 13.7%
      vs II: 24.7%; p < 0.01), without a detected increase in complications of
      hemorrhages. CONCLUSIONS: For a variety of factors, the number of elderly
      patients admitted with complicated AMI has increased. In our experience the
      simple modification in the way thrombolysis is prescribed is capable of
      restraining the hospital death rate ratio.

PMID- 7800905
TI  - [The short-term results and angiographic predictors of subacute thrombosis in the
      coronary implantation of the Palmaz-Schatz endoprosthesis].
AB  - INTRODUCTION AND OBJECTIVES: Intracoronary stenting has been proposed as an
      adjunct to balloon angioplasty in order to improve the immediate and long-term
      results. The purpose of this study was evaluate the short-term results, subacute
      closure rate and to try to identify angiographic predictors of subacute
      thrombotic after Palmaz-Schatz stent implantation. METHODS: Through a prospective
      registry, we have evaluated in 500 patients the safety and efficacy of Palmaz
      Schatz stent implantation (580 in total) in coronary arteries and saphenous vein
      grafts. The identification of clinic and angiographic predictors of subacute
      closure have been evaluated with the assistance of a BMDP statistical software
      using an univariate and multivariate statistical analysis (logistic regression).
      The determination of diameter and stenosis has been achieved by electronic
      caliper. RESULTS: The stent was implanted successfully in 98.6% of the patients.
      There was no abrupt closure (< or = 1 day), however 36 patients (7.2%) developed
      subacute thrombotic closure (among 2nd-21st day after stenting). The major
      complications were: death 9 patients (1.8%), bypass surgery 7 patients (1.4%) and
      myocardial infarction 21 patients (4.2%). The predictors of subacute thrombotic
      closure through univariate statistical were: stenting for bail-out (S.T.: 27%; p
      < or = 0.0001), multiple stenting (S.T.: 24.1%; p < or = 0.0001), final diameter
      stent < or = 3.25 mm (S.T.: 12.6%; p < or = 0.013), and left ventricular ejection
      fraction < or = 45% (S.T.: 15.7%; p < or = 0.022). We showed with logistic
      regression that final diameter stent < or = 3.25 mm; p < or = 0.0030, left
      ventricular ejection fraction < or = 45%; p < or = 0.0012, stenting for bail-out;
      p < or = 0.0195 and multiple stenting; p < or = 0.0252, were predictors of
      subacute thrombotic closure. CONCLUSIONS: The Palmaz-Schatz coronary stenting
      will preferably realize in those arteries bigger than 3.25 mm and left
      ventricular ejection fraction > 45%, showing multiple stenting and stenting for
      bail-out greater subacute thrombotic closure rate.

PMID- 7800906
TI  - [Cardiovascular pharmacology (VI). The current validity of old drugs: digoxin].

PMID- 7800907
TI  - [A report of a rare case of primary angiosarcoma of left atrium and a review of
      the literature].
AB  - A 66[correction of 60]-year-old female patient was admitted to hospital for
      clinical signs of pericardial tamponade. The pericardiocentesis revealed an
      hematic effusion and a left appendage mass was diagnosed by transesophageal
      echocardiography. At surgery, a left atrial tumour was resected which
      histological examination showed to be an undifferentiated angiosarcoma
      endothelioma with difficult histological classification. The tumoral screening
      was negative and the patient was discharged from the hospital. Seven months later
      the patient was readmitted for two parasternal tumours which anatomopathologic
      study revealed to be subcutaneous metastases. The rare localization in the left
      atrium and subcutaneous metastatic spread were discussed.

PMID- 7800908
TI  - [Electrical cardioversion and thrombogenesis. Apropos a case].
AB  - We report a case of a 73-years-old patient with atrial fibrillation who underwent
      direct current cardioversion. The transesophageal echocardiography performed
      before cardioversion excluded the presence of atrial thrombus. After
      cardioversion a new transesophageal echocardiography detected a thrombus in the
      left atrial appendage despite oral anticoagulation. Mechanism of thrombus
      formation and the need for oral anticoagulation before the procedure is being
      discussed.

PMID- 7800909
TI  - [Acute pulmonary thromboembolism with severe hemodynamic compromise. The efficacy
      of systemic thrombolytic treatment in the coronary unit].
AB  - A 79[correction of seventy]-year-old patient, who has been in bed a long time,
      suffered an episode of sudden dyspnea, tachycardia and tachypnea. An
      electrocardiogram registered at her admission in the coronary care unit showed a
      normal rhythm with right axis deviation and S1Q3T3 pattern and ST segment
      alterations. A ventilation-perfusion lung scanning demonstrated segmental
      perfusion defects with high probability of pulmonary embolism. She developed a
      low cardiac output syndrome, which neither responded to the volume expansion nor
      to the inotropic drugs. The bed-side hemodynamic measurements were a systolic
      pulmonary pressure of 60 mmHg, with a diastolic pressure of 18 mmHg and capillary
      wedge pressure of 13 mmHg with high pulmonary resistance. With this evidences,
      the diagnoses of massive pulmonary embolism was done, thrombolytic treatment was
      decided on. Two hundred and fifty thousands international units of streptokinase
      was administered, and then 100.000 UI/hour in 24 hours; after that with
      intravenous heparin. The low cardiac output syndrome disappeared. The patients
      recovered her systemic arterial pressure and her diuresis. The
      electrocardiographic signs vanished and both the pulmonary pressure and
      resistance decreased. We discussed the importance of intravenous thrombolytic
      treatment in massive pulmonary embolism. We concluded than this treatment is an
      useful strategy that not always needs a pulmonary arteriography, and could be
      used in low complexity centres, successfully in the massive pulmonary
      thromboembolism with severe hemodynamic damage.

PMID- 7800910
TI  - [A heart transplant in a patient with doxorubicin-induced myocardiopathy as a
      complication of the treatment of a lymphoma].
AB  - We present the case of a young man who developed severe cardiomyopathy eight
      years after receiving high-dose doxorubicin therapy as treatment for diffuse
      lymphoblastic lymphoma. He underwent cardiac transplantation and eighteen months
      later the tumor has not recurred and the patient has no cardiac symptoms.

PMID- 7800911
TI  - [The toxicity of slow-release verapamil and chronic kidney disease].

PMID- 7800912
TI  - Glutathione S-transferase in normal human anagen hair follicles.
AB  - Glutathione S-transferase (GST) has been quantified and characterized in healthy
      human anagen hair follicles obtained from 36 men and 36 women (26 +/- 7 years of
      age). GST activity was determined using 1-chloro-2,4-dinitrobenzene as a
      substrate, and the values in men were: 0.5 +/- 0.2 mU/follicle, significantly
      different from women (0.36 +/- 0.2 mU/follicle); 196 +/- 98 mU/mg protein and 309
      +/- 158 mU/mg DNA without significant differences from women. Enzyme activity
      showed a high degree of inter-individual variability (23.5-fold when expressed
      per follicle, 18.29-fold expressed per mg of protein and 22.75-fold per mg of
      DNA) in the whole population and this variability was higher in women. Ion
      exchange chromatography by KCl and enzyme immunoassay suggest that the GST
      present in hair follicles corresponds with the acidic form. The percentage of
      anagen hairs in each subject showed a positive correlation with the following
      parameters: GST/hair, GST/DNA and DNA/hair. It is concluded that GST may
      contribute to the maintenance of the hair growth cycle.

PMID- 7800913
TI  - VIP suppression in the intestine and cerebral cortex following administration of
      VIP antiserum to newborn rats.
AB  - The administration of vasoactive intestinal peptide (VIP) antiserum to newborn
      rats significantly reduced the VIP content, both in the cerebral cortex and in
      intestinal epithelial cells. The decrease was observed at postnatal days 14 and
      21 and also in 90 day-old animals. The neonatal treatment produced a significant
      increase in the density of high- and low-affinity binding sites for VIP in the
      cerebral cortex at post-natal days 14 and 21 whereas in the intestinal epithelial
      cells only the low-affinity binding sites were up-regulated at the same time
      points. VIP suppression induced by neonatal administration of the corresponding
      antiserum may represent a useful approach to further characterize the
      physiological role of this neuropeptide.

PMID- 7800914
TI  - Plasma amino acids in hyperphagic pups subjected to a glucose gavage.
AB  - An oral gavage of either glucose or saline was given to pups fed either standard
      diet or cafeteria diet. The plasma amino acid concentrations were measured by a
      radiochemical method. In the standard diet group, plasma Asn+Asp, Thr, Pro, Cit,
      Trp and Phe levels were higher in rats receiving a glucose solution than in those
      given saline solution; taurine (on day 20) and Ser (on day 30) showed also higher
      plasma values. Plasma Arg and taurine levels in rats receiving glucose were lower
      than those in rats receiving saline when these pups were fed the cafeteria diet.
      Tyr (on day 20) and Gly and Pro (on day 30), showed decreased plasma values. The
      diet consumed during the days preceding a glucose gavage may have pronounced
      effects on several metabolites, particularly on nitrogen metabolism. The
      homeostasis of plasma amino acids was held highly constant in spite of the
      variety of diets supplied, indicating a remarkable homeostatic capacity on amino
      acidemia against dietetic manipulation.

PMID- 7800915
TI  - A bilateral study of aminopeptidase activity in the adrenal gland of young and
      aged rats.

PMID- 7800916
TI  - Effect of thyroxine on the rate of collagen breakdown in young thyroidectomized
      male rats.

PMID- 7800917
TI  - Stimulation of brush border enzyme activity along the rat small intestine by
      misoprostol.
AB  - The effect of Misoprostol (0.3 mg/kg b.w., orally for four weeks) on the brush
      border membrane enzyme activity, is studied in growing rats. Misoprostol enhanced
      stomach and intestine relative weights as well as the mucosal weight of the
      duodenum and proximal jejunum. In treated rats, disaccharidases, alkaline
      phosphatase and aminopeptidase enzyme activity were measured in brush border
      purified fraction throughout the small intestine. Sucrase, maltase,
      aminopeptidase and alkaline phosphatase specific activities were significantly
      increased along the small intestine. In the proximal jejunum, sucrase (62%; p <
      0.001) and maltase (42%; p < 0.01) activities were significantly greater. Sucrase
      activity was also significantly (p < 0.001) increased by about 103% in the distal
      jejunum. There was also a significant (p < 0.05) increment of 32% in the duodenal
      and ileal alkaline phosphatase activity after treatment. Similarly,
      aminopeptidase activity was significantly (p < 0.05) higher in duodenum (67%) and
      jejunum (24%). In conclusion, Misoprostol appreciably increased the ability of
      the small intestine to perform its digestive functions although further studies
      will be necessary to examine the cellular and molecular mechanism(s) which may be
      responsible for these effects.

PMID- 7800918
TI  - Effects of acute intravenous ethanol on basal exocrine pancreatic secretion in
      rat: cholinergic involvement.
AB  - The effect of intravenous infusion of ethanol on the basal exocrine pancreatic
      secretion of anesthetized rats was studied. The cholinergic involvement on the
      actions of ethanol was also studied using previously atropinized animals. During
      the stimulation period, pancreatic flow rate was significantly increased by
      intravenous ethanol in both un-atropinized (199% compared with basal) and
      atropinized rats (195% compared with basal). Pancreatic protein output was also
      increased during ethanol administration in both groups of animals (171% and 165%
      compared with basal in, respectively, un-atropinized and atropinized rats). After
      the administration of ethanol, in the poststimulation period, pancreatic flow
      rate was further increased only in the atropinized group of rats (290% compared
      with basal), whose values were significantly higher than those of ethanol-treated
      un-atropinized animals (195% compared with basal). A similar profile of response
      was observed in pancreatic protein output. Since intravenous ethanol did not
      stimulate either secretin or VIP release to portal plasma, the present results
      point to a direct effect of this substance on the exocrine pancreas. Furthermore,
      atropine revealed the existence of an inhibitory cholinergic effect of ethanol on
      the exocrine pancreas. In summary, results show that the effect of intravenous
      ethanol on the basal exocrine pancreatic secretion is dual and antagonistic.

PMID- 7800919
TI  - The effect of hypo-, normo-, and hypercapnia induced by mechanical ventilation on
      intrapulmonary shunt.
AB  - The effects of hypo-, normo- and hypercapnia on the variations in arterial
      oxygenation and their indices in critical patients with acute respiratory failure
      (ARF) receiving mechanical ventilation are studied. It is a prospective and
      randomized study carried out in multidisciplinary ICU. Fifteen ARF patients,
      intubated and mechanically ventilated, were studied within the first 48 h of
      evolution. Three stages were delimited: I) 30 min after the beginning of
      anaesthesia; II) 30 min after adding 30 cm of dead space (VD); III) 30 min after
      replacing the previous VD with VD of 60 cm. Ventilation parameters and FiO2 were
      kept stable. Stage I was characterized by respiratory alkalosis and stage II by
      normal acid-base balance with an increase in PaO2 (p < 0.01) and a decrease in
      intrapulmonary shunt (Qsp/Qt) (p < 0.001); the indices alveolar to arterial
      oxygen tension gradient [P(A-a)O2], respiratory index (R.I.) and estimated shunt
      (Est Shunt) also decreased significantly, whereas arterial to alveolar oxygen
      tension ratio (PaO2/PAO2) and arterial oxygen tension to inspired oxygen fraction
      ration (PaO2/FiO2) increased significantly. In stage III there was pure
      hypercapnic acidosis, with decreases in PAO2 (p < 0.001), P(A-a)O2 (p < 0.01) and
      R.I. (p < 0.05), while PaO2, Qsp/Qt, Est Shunt, PaO2/PAO2 and PaO2/FiO2 remained
      stable with respect to the previous situation. The observed PaO2 differs (p <
      0.05) from the expected PaO2 in stage III. It is suggested that local or regional
      modifications of pulmonary perfusion are responsible for the observed variations.
      The P(A-a)O2 and R.I. indices do not make it possible to differentiate the causes
      of arterial hypoxemia in the presence of hypercapnia.

PMID- 7800920
TI  - Effect of antiprogestagen RU486 on both natural and prolactin-induced
      morphological luteolysis in rat..
AB  - Adult female cyclic rats were hypophysectomized and their pituitary glands
      autotransplanted beneath the left kidney capsule (Aptr) on day 1 (metestrus). To
      induce the luteolytic effect of prolactin (PRL) the rats were injected s.c. with
      0.4 mg of 2-bromo-alpha-ergocryptine (CB154) on cycle days 12, 13 and 14. Other
      groups of Aptr rats were injected daily with CB154 or ethanol vehicle from day 12
      to day 23. To study the role of progesterone (P) on the luteotrophic effect of
      PRL as well as on the natural and on the PRL-induced luteolysis, rats without
      CB154 treatment or with long or short CB154 treatment were injected s. c. with 2
      mg of the antiprogestagen RU486 or 0.1 ml oil from day 1 to day 23. From each rat
      the mean weight of the corpus luteum (CL) was noted on day 24. The serum PRL
      level rose from day 1 to day 12 and fell thereafter by day 15 in CB154-treated
      rats. The serum level of PRL rose again in short term CB154-treated rats, and
      remained low in long term CB154-treated rats. No effect of RU486 on serum PRL
      levels was noted in any group. The serum P level fell rapidly as the treatment
      with CB154 began after day 12. Neither the rise in serum PRL after day 15 in
      short term CB154-treated rats nor RU486 treatment affected the P level. Treatment
      with RU486 did not affect the CL weight on day 24 in ethanol vehicle injected
      rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7800921
TI  - [Changes in drug therapy and in seizure frequency in an institution for epilepsy
      patients between 1971 and 1986].
AB  - Trends in treatment of epilepsy in an institution for handicapped patients with
      epilepsy were investigated in a retrospective longitudinal study. Medications and
      seizure frequencies in the period 1971 to 1986 were compared in 663 patients
      living in the institution at least since 1971. The results show that the majority
      of patients were on polytherapy, being treated on average with 2.95 (1971) to
      2.60 (1986) anticonvulsants. The use of phenytoin, primidone and the succinimides
      clearly declined; the use of phenobarbitol declined slightly. The use of
      carbamazepine and valproic acid and their mean doses increased. The mean serum
      concentration of most of the anticonvulsants studied tended to move into the
      "therapeutic" range. The primidone and phenytoin concentrations remained rather
      low. The frequency of seizures, in particular of grand mal seizures, decreased
      between 1971 and 1981; from 1981 to 1986, no clear trend could be established.
      The results are compared with those of studies carried out in various other
      countries. It is discussed whether special antiepileptic therapy is required for
      the treatment of handicapped patients.

PMID- 7800922
TI  - [Follow-up of 64 patients with traumatic and atraumatic craniocerebral lesions--a
      needs analysis of up-to-date rehabilitation possibilities].
AB  - A critical examination was carried out on 64 selected case histories of
      craniocerebral trauma patients, with extraction of as exact data as possible
      concerning each patient's disease course a difficulty. The majority of the
      patients severely injured, the study elicited problems during early
      rehabilitation and discusses the patients' outcomes in view of their vocational
      and social reintegration. Also dealt with are the problems met with relative to
      course observation and documentation. Later phases of rehabilitation frequently
      are complicated by functional loss and deficits, and long waiting lists run
      counter to the basic idea of early rehabilitation. Treatment shortcomings during
      the early phase of the acute neurological condition are indicative of the
      patients' future fate. Discussed is the relevance of rating scales for assessing
      the course of severe conditions. In view of an ongoing state-of-the-art
      discussion concerning the concept of neurological early rehabilitation in the
      narrower sense, a clearly structured treatment approach specifying minimum
      requirements in terms of staffing, contents, and methods, as well as systematic
      internal quality control efforts are demanded.

PMID- 7800923
TI  - [The significance of quantitative computerized tomography in the long-term
      prognosis of ischemic stroke].
AB  - The courses of 118 patients who had suffered a supratentorial ischaemic
      infarction were observed over a mean follow-up period of 4 years. One goal of
      this study was to assess the prognostic value of quantitative cranial
      computerized tomography (CT). The infarct volume was determined using CT and
      expressed quantitatively as a percentage of the total brain volume. The infarct
      volume correlated negatively with the global outcome as estimated by the Barthel
      Index. It correlated positively with the occurrence of psychiatric alterations,
      disturbances of consciousness or alterations in the EEG. Nicotine, alcohol
      consumption and hyperuricaemia were the most frequent risk factors identified for
      men, while for women, especially those over 60, cardiac diseases were the most
      relevant risk factors. In looking only at the older patients, age, psychiatric
      alterations and cardiac disease at the time of the stroke were unfavourable
      prognostic factors. CT lesions in the basal ganglia were also unfavourable
      prognostic factors. Infarcts in the posterior cerebral artery region were seen as
      prognostically favourable. During the 4-year follow-up period, the reinfarction
      rate was 26%. Nearly 50% of the total patient population died. This group was
      significantly older, had more psychiatric alterations as well as multiple infarct
      areas in CT.

PMID- 7800924
TI  - [Patient cooperation as a problem in inpatient psychosomatic rehabilitation].
AB  - Patients insured under the pension insurance scheme are subject to a statutory
      obligation to cooperate in their remedial treatment. In in-patient psychosomatic
      rehabilitation, a number of problems arise in view of this cooperation, as the
      patients are hampered in their potential for compliance with this demanded
      cooperation due to the specific nature of their psychosomatic condition, their
      personality structure as well as their previous disease history. Moreover,
      cooperation in psychosomatic rehabilitation involves special requirements in
      terms of active participation, inner openness and readiness for psychosocial
      change. In psychosomatic rehabilitation, the patient's cooperation cannot be
      assumed as a matter of course, rather, it is a task of the treatment process
      itself, which by appropriate therapeutic means seeks to achieve the patient's
      motivation and a working alliance, hence to create the prerequisites for
      cooperation.

PMID- 7800925
TI  - [Integrated therapy approach in the inpatient rehabilitation of women and men
      with total gastrectomy for stomach carcinoma].
AB  - On the basis of the documented course of 83 in-patient rehabilitation procedures
      in 28 female and 55 male patients who had undergone total gastrectomy due to
      cancer of the stomach, "objective" and "subjective" data were analyzed and
      correlated within an integrative treatment concept in order for one, to obtain as
      rehabilitation-specific a description as possible of how patients cope with the
      conditions resulting from their illness, and for the other, to contribute to
      furthering a multidisciplinary treatment concept, uniting the medical and
      psychosocial lines of approach. "Objective" data, i.e., data based on therapist
      assessments, inter alia include laboratory and other measures, diagnostic and
      therapeutic interventions and their gradings, sociomedical and psychosocial
      parameters, Karnofsky index, as well as Edinburgh Rehabilitation Status scores,
      while "subjective" ones, i.e., data based on the patients' own estimates,
      included symptom scores and judgements relative to treatment course and the so
      called therapeutic environment. Findings are presented in detail for both planes
      (i.e., "objective" and "subjective" parameters) and discussed in light of
      pertinent literature. In particular the "missing" (yet perhaps expected)
      correlations among these planes are considered indicative of an urgent need for
      inclusion of the patient's behaviour and experience in the rehabilitative
      therapeutic process. The partially surprising gender differences found are
      discussed with a view to behavioural patterns that might be conducive to coping
      with the malignant disease and its sequelae, an integrative treatment approach
      found to be of utmost importance, in particular in terms of the (therapeutic)
      relationship with self and others.

PMID- 7800926
TI  - [Possibilities of driver fitness diagnosis and training using a stationary
      training car].
AB  - The study presented had dealt with the potential of a stationary training car in
      assessing and improving the driving skills of patients having neurological
      disorders, with reaction testing and reaction training carried out by means of
      the training car. The aim had been to verify whether, and to what extent, such a
      device might contribute to driving fitness diagnosis and improvement. The sample
      was comprised of patients who, mostly following brain injury, participated in an
      in-patient rehabilitation programme. It was found that an individual's driving
      fitness cannot be diagnosed on the basis of laboratory testing alone. The
      deficits elicited by the tests have to be verified concerning their impact in
      real road traffic in every individual case, taking adaptive potential into
      account. In view of improved driving skills, the findings show performance
      improvements in various reaction tests as well as better driving sample ratings.

PMID- 7800927
TI  - [Could disregard for the "disabled" be modified by linguistic methods?--an
      impetus to ponder].

PMID- 7800928
TI  - [Xavier and his friends--travel by a Munchener wheelchair dance group through
      Ecuador in October 1993].

PMID- 7800929
TI  - [The "elderly of the Future--Tomorrow's Society"--future congress of the Federal
      Ministry of Family and Seniors on 8-25-1994 in Bonn].

PMID- 7800930
TI  - Effects of anti-progesterone compound RU486 on ovulation in immature mice treated
      with PMSG/hCG.
AB  - The effects of RU486, a competitive antagonist of progesterone, on ovulation were
      studied in PMSG/hCG-treated immature mice. PMSG/hCG was administered to 3-week
      old female mice to induce ovulation. A dose of 0.5 mg of RU486 was administered 3
      h before hCG injection, simultaneously with hCG injection, or 3, 4.5, 6, 7.5 or 9
      h after hCG administration. The lowest number of ovulated eggs was observed in
      the group given RU486 6 h after hCG injection. Although the mean number of
      ovulated eggs was only 4.4 in this group, it was increased to 25.7 by
      supplementary administration of 2.0 mg of progesterone. It was demonstrated that
      RU486 had inhibitory effects on ovulation, and the inhibition could be prevented
      by supplementary administration of progesterone.

PMID- 7800931
TI  - Regeneration of splenic stromal elements.
AB  - Splenic regeneration represents an interesting phenomenon both in relation to its
      role as a model system (to study the development of the complex three-dimensional
      architecture of an immunological organ) and because of the clinical application,
      namely autotransplantation of spleen. The latter is one of the attempts to
      restore splenic functions after splenectomy, which is known to increase a life
      long risk of fatal sepsis. However, splenic functions of autotransplanted splenic
      tissue are known to be highly dependent on the recovery of the complex
      microenvironment and immunoarchitecture of the splenic compartments during the
      regeneration processes, but the elements inducing splenic reorganization are
      still unknown. Therefore, the present work investigates whether splenic stroma
      depleted of cells is able to induce regenerative processes after implantation. In
      addition, we tried to recombine stromal tissue with selected cell populations to
      study their influence. Cell-free stromal tissue induced angiogenesis and to a
      lesser extent also attracted the immigration of lymphocytes during the first 60
      days of regeneration. However, after this period of regeneration, the transplants
      began to degenerate and were resorbed. The recombination of stromal tissue with
      mitogen-stimulated spleen cells only resulted in intensifying the degenerative
      processes, and all implants were resorbed after 120 days. Except that in the
      first 30 days there were some accumulations of lymphocytes that resembled
      primitive follicles, no splenic compartments such as red pulp, periarteriolar
      lymphoid sheath, or marginal zone could be detected in any of the transplants.
      From these results it can be concluded that splenic stroma can induce the primary
      events of splenic regeneration (like angiogenesis), but is not able to provide an
      appropriate microenvironment and immunoarchitecture for a correct repopulation
      and differentiation of cells. Furthermore, the recombination experiments point to
      a minor role of T-cells and possibly an important role for accessory cells in
      splenic regeneration.

PMID- 7800932
TI  - Morphine effects on the release of glucagon, insulin and somatostatin from the
      isolated, perfused rat pancreas.
AB  - The pancreatic glands from six male Wistar rats weighing between 200 and 250 g
      were isolated and perfused. After 30-min equilibration and 20-min basal periods,
      perfusion with 0.2 mg/ml of morphine for 20 min resulted in a significant (P <
      0.05) increase in insulin release, with no changes in release of gucagon or
      somatostatin. After a recovery period of 20 min, a higher morphine concentration
      of 2 mg/ml was introduced for another 20-min period. With this morphine dose
      there were significant increases in release of insulin (P < 0.05), glucagon (P <
      0.01) and somatostatin (P < 0.05). This shows that morphine induces the release
      of insulin, glucagon and somatostatin from pancreas in a dose-dependent way, and
      that release of insulin and glucagon is not primarily affected by regulation of
      somatostatin levels.

PMID- 7800933
TI  - Kupffer cell function in chronic liver injury and after partial hepatectomy.
AB  - The reticuloendothelial system (RES) plays an important role in the biological
      defense system. In the liver, Kupffer cells are the main constituent of the RES,
      and when their function is impaired postoperative complications may more often
      occur. By using 99mTc-labeled human serum albumin millimicrospheres (99mTc-HSA
      MM) combined with assessment of single photon emission computed tomography
      (SPECT), we have attempted to determine the function of Kupffer cells
      independently of the hepatic blood flow. First, Kupffer cell function in rats
      with chronic liver injury caused by CCl4 was studied. The hepatic uptake rate in
      chronic liver injury was decreased, and a reduced phagocytic activity of the
      Kupffer cells was noted. The parameter concerning Kupffer cell degradation, the
      excretion rate (k), was markedly decreased in the early period of chronic liver
      injury. Changes in Kupffer cell function after 30% and 70% hepatectomy were also
      studied. After 30% hepatectomy, the excretion rate was decreased on the first
      postoperative day (POD), and it was increased beyond that found after sham
      operation on the 3rd POD. In contrast, slower recovery of uptake rate was
      demonstrated. After 70% hepatectomy, both uptake and excretion rates were
      markedly reduced, and recovery was prolonged beyond the 5th POD. The hepatic
      uptake was not parallel with the excretion rate in either experiment. These
      results suggest that the method that measures the hepatic excretion rate may
      provide a better assessment of Kupffer cell function than the current uptake
      measurement with radiolabeled colloid.

PMID- 7800934
TI  - Post-traumatic dynamic change of carboxyterminal propeptide of type I
      procollagen, alkaline phosphatase and its isoenzymes as predictors for enhanced
      osteogenesis in patients with severe head injury.
AB  - Patients suffering from severe head injury and fractures of long bones or large
      joints often show enhanced osteogenesis, with hypertrophic callus formation
      and/or heterotopic ossifications. The advantage of this phenomenon is early
      consolidation of the fractures. An extreme disadvantage is extensive
      periarticular calcification, resulting in complete ankylosis of the affected
      joint. In spite of numerous efforts aimed at clarifying the way in which severe
      head injury can influence osteogenesis at a distant site, this phenomenon is
      still not understood. The process, once started, seems irreversible, but if
      diagnosed in time, could be prevented with non-steroid anti-inflammatory drugs
      that inhibit development of heterotopic ossifications. The major prerequisite for
      testing this possibility is to define parameters of an early diagnosis of
      enhanced osteogenesis. Thus, the aim of this study was to test whether serum
      values of some parameters related to bone regeneration could allow an early
      prediction of enhanced ossification following bone fracture in patients with
      severe head injury. Samples of sera were obtained from three groups of injured
      patients: fractures of long bones or large joints only (n = 6), severe head
      injury only (n = 8), severe head injury and fractures of long bones and large
      joints (n = 7) and from a group of apparently healthy volunteers (n = 10). The
      values for alkaline phosphatase (ALP), the bone isoenzyme, and the carboxy
      terminal propeptide of type I procollagen (PICP) were significantly higher (5-20
      times as high) in patients with severe head injury and bone or joint fractures
      than in any other group. Significantly increased concentrations of PICP were
      already found in the 1st week after injury, and those of ALP and of the bone
      isoenzyme increased during the 2nd week after injury. Results show that these
      parameters are helpful for an early diagnosis of enhanced osteogenesis and
      heterotopic ossifications in patients with severe head injury and bone fractures.
      Further studies are necessary to verify these findings, while analysis of reasons
      for the specific patterns of dynamic change of these parameters could lead to
      better understanding of the mechanisms underlying the uncontrolled bone
      formation.

PMID- 7800935
TI  - Polyerga, a biological response modifier enhancing T-lymphocyte-dependent
      responses.
AB  - Cancer patients are often treated with biological response modifiers to enhance
      immunological functions. However, little is known about the actual mechanism of
      action of many of these substances. Therefore, we were interested in the effect
      of i.p. treatment with porcine low-molecular-weight spleen peptides, which are
      used during supportive cancer therapy, on lymphoid cell populations and function
      in mice. After treatment with 0.5 microgram peptides/kg body weight for 14
      consecutive days, lymphokine secretion and the generation of cytotoxic T-cells
      were significantly enhanced as compared with controls. However, there was no
      effect on the number of cells or the percentage of cells expressing functional
      surface markers in secondary lymphoid organs.

PMID- 7800936
TI  - The involvement of muscarinic receptors in gastric liquid emptying in the
      conscious rat following Roux-en-Y-antrectomy.
AB  - The gastric emptying of liquid test meals is dependent on resistance to flow at
      the pylorus and on pressure gradients between the duodenum and the body of the
      stomach. In the present study, we investigated the role and subtypes of
      muscarinic receptors during gastric emptying of various liquid test meals in
      conscious rats with gastric fistula after Roux-en-Y antrectomy. In the control
      rats with gastric fistula but with intact reflex pathways and pylorus, the non
      selective muscarinic antagonist atropine (7 mg/kg i.p.) and M1-selective
      pirenzepine (7 mg/kg i.p.), acting possibly on M1 receptors, delayed saline
      emptying by suppressing cholinergic tone and thus relaxing the body of the
      stomach and contracting the pyloric sphincter. On the other hand, in Roux-rats
      saline and hyperosmolal saline emptying were not significantly affected, while
      the inhibitory effect of HCl was completely reversed. Furthermore, peptone
      induced delay of gastric emptying in control rats was also reduced in Roux-rats.
      Pirenzepine abolished the facilitating effects of Roux-en-Y operation on acid and
      peptone emptying and M2-selective antagonist AF DX-116 (7 mg/kg i.p.) did not
      have any inhibitory effect in this regard. In conclusion, Roux-en-Y gastrectomy
      without vagotomy does not slow gastric emptying of liquids, and it reverses the
      inhibitory effects of peptone and acid through an atropine- and pirenzepine
      sensitive pathway.

PMID- 7800937
TI  - Functions of macrophages and accessory cells in HIV and other lentivirus
      infections. Le Bischenberg, France, October 13-15, 1993. Symposium proceedings.

PMID- 7800938
TI  - Cellular adherence enhances HIV replication in monocytic cells.
AB  - Cellular adherence is important for monocyte migration and function and is known
      to induce monocyte activation, leading to the production of mRNA for several
      proto-oncogenes and cytokines. In addition, since cellular adherence has
      important intracellular signalling function, it has the potential to enhance
      human immunodeficiency virus (HIV) replication in monocytic cells. We have
      investigated the effects of adhesion of the monocytic cell line THP-1 transfected
      with HIV1 or HIV2 long terminal repeat chloramphenicol acetyltransferase (LTR
      CAT) constructs. These studies have shown that adherence to tissue culture
      plastic or confluent endothelial cells is essential for enhanced HIV LTR CAT
      expression in lipopolysaccharide-stimulated cells. In addition, we have
      investigated the effects of engagement of specific adhesion molecules, using
      immobilized antibodies, on HIV replication in the promonocytic cell line OM101,
      which contains a single latent proviral copy of HIV. Such studies have
      demonstrated that engagement of CD18, the beta subunit of the lymphocyte function
      related antigen-1 (LFA-1) and major histocompatibility complex class II (MHC II)
      enhanced HIV replication. LFA-1 is involved in both monocyte-endothelial cell
      interactions and monocyte-T-cell interactions, and MHC II is involved in monocyte
      interaction with antigen-specific T cells. These data suggest that such
      interactions of membrane adhesion molecules with their appropriate ligand enhance
      HIV replication in vivo. Thus, this study has demonstrated that cellular
      adherence is a key regulatory factor of HIV replication in monocytic cells.

PMID- 7800939
TI  - Restricted expression of HIV1 in human astrocytes: molecular basis for viral
      persistence in the CNS.
AB  - Besides macrophages and microglial cells, cells of astroglial origin are thought
      to be targets of HIV1 in the brain. HIV1 infection of astroglial cells results in
      restricted production of the virus. To analyse the molecular basis of this
      restricted infection phenotype, we established a chronically HIV1-infected low
      producer astrocytoma cell line. These cells show only low levels of mRNA encoding
      structural proteins, due to a cell-determined blockage in the Rev/RRE regulatory
      axis. The low-producer state could not be overcome by treatment with known
      stimulators of virus expression such as phorbol ester, (12-O-tetradecanoylphorbol
      13-acetate), tumour necrosis factor alpha or sodium butyrate. This indicates that
      the molecular mechanisms involved in restricting virus production in astroglial
      cells differ from those in latently infected T cells and monocytes.

PMID- 7800940
TI  - In vitro HIV1 infection of human cervical tissue.
AB  - Heterosexual intercourse is the major mode of transmission of the human
      immunodeficiency virus (HIV) worldwide. Heterosexual transmission of HIV is
      particularly important in Africa and is increasing in the developed world. The
      mechanism of HIV infection of the female genital tract with HIV and subsequent
      events leading to clinical infection are not fully understood. In particular, the
      primary cellular targets of HIV infection in the female genital tract have not
      been determined. We have established an in vitro model for studying HIV infection
      of the human adult cervix by HIV. Human cervical mucosal explants were briefly
      exposed to HIV strains of different tropism and maintained in organ culture for 7
      days. HIV infection detected by immunohistochemistry and in situ hybridization
      was only observed in cervical explants exposed to macrophage tropic strain HIV1Ba
      L. HIV-infected cells were located in submucosa and had the morphology and
      distribution of macrophages. While CD4+/CD3+ T cells were still present at day 7
      in the organ culture tissue, no infection of cervical explants was seen with T
      cell tropic strains even in the presence of phytohaemagglutinin and IL2. This
      model system will enable study of the dynamics of HIV infection of the human
      cervix and analysis of possible prophylactic or therapeutic strategies.

PMID- 7800941
TI  - Effect of an elevated temperature on the replication of HIV1 in a monocytic cell
      line.
AB  - Physical parameters may affect viral replication by preventing or limiting the
      expression of viral genes. The effect of a supraoptimal temperature (39 degrees
      C) on the production of HIV1 was investigated in promonocytic latently infected
      U1 cells. The amount of viral particles released from the cells 2 days after TNF
      alpha and/or IL6 stimulation was lower at 39 degrees C than at 37 degrees C, and
      this was not a consequence of an intracellular accumulation of virions at 39
      degrees C. Cell viability and metabolism at 39 degrees C were not modified when
      compared to those at 37 degrees C, and the TNF alpha activation system was
      unaltered at high temperature. We hypothesized that a stage of the viral
      replication was affected at 39 degrees C; accordingly total RNA were prepared and
      hybridized, after Northern Blot, with a virus-specific probe. The RNA coding for
      structural proteins (9.2 and 4.3 kb) were present in lower amounts at 39 degrees
      C, whereas the abundance of those coding for regulatory proteins was almost
      unaltered. Our results show that the accumulation of single-spliced and unspliced
      transcripts is lower at 39 degrees C than at 37 degrees C, suggesting an
      implication of the Rev protein in this inhibition.

PMID- 7800942
TI  - Detection of HIV DNA in peripheral blood dendritic cells of HIV-infected
      individuals.
AB  - Previous studies from this laboratory indicated infection of dendritic cells (DC)
      from peripheral blood of individuals infected with HIV1. Here, further evidence
      for the infection of peripheral blood DC with HIV1 is presented. Low-density
      cells (LDC) were prepared from blood mononuclear cells of HIV-infected
      individuals at different clinical stages of disease. These cells are enriched (10
      40%) for MHC class-II-bearing DC, while most of the remaining cells are
      monocytes, and 2-10% are lymphocytes. A quantitative polymerase chain technique
      (PCR) was used to estimate the HIV provirus load in LDC and lymphocytes of
      patients in different disease categories. HIV provirus was detected in every LDC
      preparation, and for many individuals, particularly CDC stage IV patients, the
      load was higher in the LDC than in the lymphocyte fraction. These findings
      suggested that patient DC are infected with HIV. In order to provide confirmatory
      evidence for this conclusion, PCR was performed on DC that were highly purified
      from LDC by panning to remove contaminating T, B, natural killer and monocytic
      cells. High levels of HIV provirus were found in these purified DC. These
      findings suggest that DC provide a reservoir of HIV and that the consequences of
      such infection may be relevant to the development of disease.

PMID- 7800943
TI  - Are follicular dendritic cells, macrophages and interdigitating cells of the
      lymphoid tissue productively infected by HIV?
AB  - Numerous data demonstrate that lymphoid tissues represent a major HIV reservoir
      and sites of virus replication. To gain more information about the phenotype of
      cells in which HIV replicates in the lymphoid tissue, we applied HIV RNA
      hybridization technique in combination with immunohistochemistry on 10 lymph
      nodes and 2 lymphoepithelial cysts (LEC) of the parotid gland. In addition, to
      determine whether or not follicular dendritic cells (FDC) are important targets
      for HIV, we also analysed isolated and sorted FDC from 4 lymph nodes. The tissues
      showed follicular hyperplasia and heavy RNA signals in the germinal centres (GC),
      where diffuse labelling in the light zone as well as single cells with > 50
      silver grains were present. The extrafollicular parenchyma contained only a few
      productively infected cells. The diffuse labelling was intimately related to the
      FDC network. However, electron microscopic examination and in situ hybridization
      on isolated FDC did not provide convincing evidence for virus replication in
      these cells. Virus-producing cells in the GC were almost exclusively CD45RO+,
      CD57- T cells. Macrophages with HIV RNA were mainly found in LEC of the parotid
      gland. S-100+ interdigitating cells of the T-dependent zone were HIV RNA-.
      However, some large S-100+ cells in the squamous epithelium covering the LEC or
      lying subepithelial did express HIV RNA. These findings suggest that local
      factors (cytokines?) in the lymphoid tissue probably influence the expression of
      HIV.

PMID- 7800944
TI  - In vitro analysis of HIV- and non-HIV-infected monocytes/macrophages from healthy
      subjects and patients with malignant tumours.
AB  - Phenotype and release of IL1 alpha, IL6 and TNF alpha were examined in monocytes
      derived from 14 healthy donors and 24 tumour patients in a long-term culture
      using immunohistochemical, RNA in situ hybridization and ELISA techniques. After
      stimulation with LPS and IFN-gamma, blood monocytes and resulting macrophages
      showed an overall decrease in cytokine release from the 6th to the 48th day of
      culture, both with and without HIV infection. HIV infection provided a strong
      stimulus for IL6 production and a weak stimulus for IL1 alpha production, whereas
      TNF alpha release decreased after HIV infection. Non-HIV-infected
      monocytes/macrophages from patients with malignancies showed significantly
      reduced cytokine production after stimulation, in comparison with
      monocytes/macrophages from healthy subjects. In vitro HIV infection of monocytes
      from tumour patients caused severe depression of cytokine production during the
      whole time of observation. In all experiments a parallel was observed between the
      extent of cytokine release and the presence of young/early inflammatory
      macrophages as identified by the antibody MAC387/27E10 in situ. In contrast,
      cytokine expression assessed semiquantitatively by immunohistochemical staining
      in situ showed discordant development, since it increased during long-term
      culture, while supernatant concentrations of cytokines declined. Simultaneously,
      significant cytokine RNA levels could be found in macrophages from the 6th to the
      24th day of culture, as detected by in situ hybridization. After 48 days of
      culture, no more cytokine RNA was detectable, while macrophages continued to
      exhibit distinct immunohistochemical positivity for cytokine antibodies. From
      these results, it is concluded that macrophages kept in culture for a long period
      become inhibited in their secretion. HIV has an ambivalent effect on cytokine
      production in Mo/Mac, resulting in an increase in IL6 and IL1 as well as a
      decrease in TNF alpha production. Mo/Mac of non-HIV-infected tumour patients show
      significantly reduced cytokine production in comparison with Mo/Mac from healthy
      subjects. The sum of the HIV infection in vitro and the tumour burden results in
      a dramatic reduction in cytokine release in Mo/Mac. This finding may provide a
      possible explanation for the specific aggressive behaviour of non-Hodgkin's
      lymphoma and Hodgkin's disease in AIDS.

PMID- 7800945
TI  - Cytokine expression of HIV-infected monocytes/macrophages at the single-cell
      level.
AB  - Monocytes of healthy donors were infected with HIV1 in vitro: 14-21 days after
      infection 50-70% of the cells produced p24 HIV1 antigen as detected with anti-p24
      immunostaining; infected cultures showed enhanced secretion of interleukin-6
      (IL6), interleukin-8 (IL8) and tumour necrosis factor alpha (TNF-alpha). The
      expression of cytokines on the single-cell level was further analysed by in situ
      hybridization using nonradioactive digoxigenin for detection. HIV1 (p24+) 
      producing cells were compared with non-HIV (p24-) -producing cells. All
      morphological subtypes of macrophages showed HIV production; no difference in
      cytokine expression was observed. Immunocytochemistry of HIV-infected and
      uninfected cultures also showed no difference in the pattern of IL1-beta, IL6,
      IL8 and TNF-alpha protein expression in the cells.

PMID- 7800946
TI  - Treatment of human monocyte-derived macrophages with a TNF alpha synthesis
      inhibitor prior to HIV1 infection: consequences on cytokine production and viral
      replication.
AB  - Human monocyte-derived macrophages (MDM) were infected with the viral strain
      HIV1/Ba-L and with the clinical isolates HIV1/DAS and HIV1/PAR. Kinetics of
      tumour necrosis factor alpha (TNF alpha) and interleukin-6 (IL6) production were
      investigated for 28 days after infection. At the early stages of infection we
      observed significant TNF alpha and IL6 secretion 2 to 10 h after infection,
      whatever the viral strain we used. During the late events of MDM infection, TNF
      alpha and IL6 were detected over 16 to 21 days following HIV1 infection, at the
      time of high viral replication. Pretreatment of MDM with a TNF alpha synthesis
      inhibitor, RP 55778, 4 h prior to HIV infection induced a modified cytokine
      pattern during the first ten hours of infection: TNF alpha production was totally
      inhibited despite comparable amounts of IL6. At the late phases of the cell
      culture, a decrease in magnitude of both viral and cytokine production as well as
      a delay in the appearance of reverse transcriptase activity and cytokine
      secretion peaks were observed in RP-55778-pretreated and HIV1-infected MDM
      cultures. Similar results were obtained after pretreatment of HIV1/DAS-infected
      MDM cultures with an anti-TNF alpha monoclonal antibody.

PMID- 7800947
TI  - Increased expression of tissue factor mRNA and procoagulant activity in ovine
      lentivirus-infected alveolar macrophages.
AB  - To link ovine lentivirus infection to lung tissue damage, we studied the
      procoagulant response in alveolar macrophages from experimentally infected lambs
      and in in vitro infected alveolar macrophages. We cloned ovine tissue factor cDNA
      and analysed its in vitro expression by Northern blotting. Visna-maedi virus
      induced tissue factor mRNA. In order to correlate this mRNA induction with its
      cellular function, we analysed macrophage procoagulant activity after in vitro
      and in vivo infection. The procoagulant activity was increased by interaction
      with the virus in both cases. Thus, visna-maedi virus-induced expression of
      tissue factor mRNA was associated with enhanced macrophage procoagulant activity.
      These findings indicate an active role of alveolar macrophages in the
      pathogenesis of these inflammatory lung lesions.

PMID- 7800948
TI  - Inhibition of HIV in vitro by antiviral drug-targeting using nanoparticles.
AB  - Nanoparticles are known to accumulate in the phagocytic cells of the mononuclear
      phagocyte system. Therefore, the use of this carrier system for the targeting of
      antiviral drugs to monocytes/macrophages (MO/MAC) is an attractive concept in the
      treatment of diseases involving MO/MAC, e.g. infection with HIV. In this study,
      the ability of macrophages isolated from peripheral blood of healthy blood donors
      to phagocytose and metabolize human serum albumin microspheres was investigated
      by transmission electron microscopy. Furthermore, nanoparticles manufactured
      using human serum albumin or polyhexylcyanoacrylate were loaded with nucleoside
      analogues (AZT and ddC) and tested for their ability to prevent HIV infection in
      MO/MAC cultures. Our results demonstrate the effectiveness of this drug-targeting
      system to one of the major target cells for HIV.

PMID- 7800949
TI  - Early events in lymph nodes during infection with SIV and FIV.
AB  - To elucidate the initial pathogenic events in lymphoid organs, the major
      reservoir of virus in HIV infection, follow-ups of viral load, pathological
      changes and target cells were performed in the rhesus macaque SIVmac251 model and
      in the cat FIV model. Lymph nodes (LN) obtained from animals sacrificed at early
      time points following experimental inoculation were analysed by in situ
      hybridization for virus load and by combined immunohistochemistry and in situ
      hybridization for virus cellular tropism. In the SIV model, the LN presented a
      high viral load at 7 days post inoculation (p.i.); at this stage, macrophages and
      T4 lymphocytes were identified as the target cells of the virus. A shift in the
      pattern of viral infection was observed at 2 weeks p.i., with a concentration of
      viral RNA in follicular dendritic cells (FDC) in the germinal centres of the
      developing lymphoid follicles. This FDC-associated virus persisted at high levels
      for 2 months p.i. in the FIV model, the number of infected cells detected in LN
      was very low compared with that found in the SIV model, and a similar role played
      by FDC was found.

PMID- 7800950
TI  - Signs of Kupffer cell involvement in productive simian immunodeficiency virus
      infection in monkey liver.
AB  - The livers of 21 rhesus monkeys inoculated with SIVmac251 were examined at 4 days
      to 39 months after infection. SIV antigens were detected in the cytoplasm of
      Kupffer cells (KC), macrophages and lymphocytes in two-thirds of the livers
      tested. The number of cells containing viral proteins substantially increased
      during the development of the disease, and KC were the main cell type displaying
      SIV proteins at an advanced stage of infection. Mature and immature lentiviral
      particles were found in cytoplasmic vacuoles or associated with worm-like
      structures in KC, indicating that SIV replication could occur within resident
      liver macrophages. Another sign of the permissiveness of KC was the formation of
      multinucleated giant cells within the hepatic sinusoids. Some of these cells
      containing 3-6 nuclei still retained ultrastructural features of KC. Most of them
      contained a high quantity of viral particles. Numerous lymphocytes displaying
      signs of apoptosis were taken up by KC, especially at the beginning of infection.
      Hyperplasia and hypertrophy of KC were noted in the course of SIV disease in the
      liver. The present data indicate that KC can be infected in vivo and may serve as
      a reservoir for SIV during the progression of the disease.

PMID- 7800951
TI  - Detection of SIV in rhesus monkey thymus stroma cell cultures.
AB  - To clarify the pathogenesis of SIV-induced thymus atrophy, the presence of SIV
      within thymus stromal cell cultures (epithelial cells, IDC, macrophages or
      fibroblasts) was investigated. The material studied consisted of 15 thymus
      specimens of rhesus macaques infected with SIVmac251 (2-4 months
      postinoculation). No viral antigen was detected, either in the cultures, by
      immunohistochemistry, or in cell culture supernatants, by ELISA (p17 antigen),
      and no viral RNA was detected by in situ hybridization. Only after coculture with
      the C8166 cell line, was virus detected in 2 out of 15 stroma cultures. The fact
      that the virus could only be detected after several passages of coculture with
      the C8166 cell line indicates that the virus exists in the thymus stroma cells in
      the form of proviral DNA. The infection of thymus stromal cells may contribute to
      the destruction of the thymus microenvironment and to the SIV-induced thymus
      atrophy.

PMID- 7800952
TI  - Contribution of the feline Langerhans cell to the FIV model.
AB  - In order to identify an equivalent of Langerhans cells in cat stratified
      epithelia, we used a panel of monoclonal antibodies known to be reactive with
      membrane antigens present on human Langerhans cells. The labelling was carried
      out by immunoperoxidase staining, for examination by light microscope, and by
      immunogold labelling, for electron microscopy. Out of 18 antibodies tested, only
      one, MHM23 antibody, specific against CD18 antigen, presented reactivity with
      dendritic epithelial cells on either frozen sections, epidermal sheets or cell
      suspension cytospins. On the ultrastructural level, these clear, dendritic, CD18+
      cells showed "zipper-like" shapes similar to Birbeck granules, which are
      characteristic ultrastructural markers of Langerhans cells. This observation
      favours the hypothesis that these CD18+ cells in cat stratified epithelia are the
      equivalent of human Langerhans cells. These labelled cells were found in all
      epidermal locations and in the mucous membranes (oral, vaginal, rectal and
      oesophageal membranes). As feline immunodeficiency virus (FIV) transmission may
      occur through these membranes, the involvement of these feline Langerhans cells
      was studied in cats seropositive for FIV.

PMID- 7800953
TI  - Liposomal doxorubicin in the treatment of AIDS-associated Kaposi's sarcoma:
      clinical, histological and cell biological evaluation.
AB  - AIDS-associated Kaposi's sarcoma (KS) in eight patients was treated with the
      systemic application of liposomal doxorubicin (20 mg/m2 per cycle). After six
      cycles of treatment a significant regression of KS was observed in all patients.
      Tumour volume was reduced from 556 +/- 635 mm3 before therapy to 42 +/- 134 mm3
      after therapy as determined by ultrasonography of selected tumours. Histological
      examination revealed a reduction of tumour-like structures and the absence of KS
      spindle cells in involved areas after therapy. In vitro experiments with KS
      derived cell cultures, which most likely represent the KS spindle cells,
      suggested that liposomal doxorubicin may cause regression of KS via two different
      mechanisms: (i) by highly specific inhibition of KS spindle cell proliferation
      and (ii) by induction of monocyte chemoattractant protein-1 expression in KS
      spindle cells, which may result in increased recruitment of phagocytic cells
      (monocytes/macrophages) into the lesions. A cooperative action of both mechanisms
      may explain the high efficacy of liposomal doxorubicin in the treatment of AIDS
      KS.

PMID- 7800954
TI  - Theophylline vs. budesonide in the treatment of mild-to-moderate bronchial
      asthma.
AB  - Eight patients with mild extrinsic asthma participated in a double-blind
      randomized intraindividual cross-over study involving 6 weeks' treatment with
      twice daily oral theophylline (2 x 1 capsules = 800 mg/day Cronasma 400) and 6
      weeks' treatment with twice daily inhaled budesonide (2 x 2 puffs = 0.8 mg/day
      Pulmicort) with nebuhaler administered in the morning and in the evening before
      eating. Lung function and carbachol provocation measured with the whole-body box
      method were performed at the beginning and after 6 weeks of treatment.
      Mucociliary clearance (MC) assessed with a scintillation camera and
      bronchoalveolar lavage (BAL) were both performed after 6 weeks of treatment. All
      patients documented daily peak flows in the morning and in the evening. [table:
      see text] Additional use of beta 2-agonists at night and during the day was not
      different for theophylline (0.10 +/- 0.39 and 1.16 +/- 2.87 puffs) and budesonide
      (0.11 +/- 0.45 and 1.97 +/- 3.02 puffs). MC (32 +/- 15% under theophylline and 33
      +/- 14% after budesonide), carbachol provocation and lung function data at the
      end of both treatment periods were the same as well as BAL data. Two patients
      needed a reduction of the theophylline dose due to nausea. This study documents
      the equipotency of theophylline (mean blood level 11.9 +/- 4.6 mg/l) and
      budesonide (2 x 2 puffs = 0.8 mg/day) in patients with mild-to-moderate asthma.

PMID- 7800955
TI  - Respiratory resistance measured by flow-interruption in a normal population.
AB  - Data on reference values of total respiratory resistance (Rint) in healthy people
      are limited. The aim of this study was to examine the relationship between Rint
      and gender, height, weight, age and smoking habits. The instrument used was the
      Jaeger Pneumoscope with a flow interruption device. The method is based on
      transient interruption of airflow at the mouth for a brief period during which
      alveolar pressure equilibrates with mouth pressure. Measurement of mouth pressure
      is used to estimate alveolar pressure prior to interruption. The ratio of this to
      the flow prior to interruption gives airway resistance. The Rint data were
      correlated with height, weight, age, gender and smoking habits in 172 healthy
      subjects. They had a normal lung function (VC, FEV1) and no signs of pulmonary
      disease. The important determining factor for the value of the Rint were height
      and age. The mean Rint of 172 subjects was 0.38 +/- 0.17 kPa.1-1.s. The average
      within-subject variability of repeated measurements of Rint expressed as
      coefficient of variation was 14.4 +/- 6.9%. Reference equation and normal values
      for Rint in a healthy population are related to height and age. The measurements
      were obtained with a commercially available interruption technique.

PMID- 7800956
TI  - Exercise hypoxemia and the effects of increased inspiratory oxygen concentration
      in severe chronic obstructive pulmonary disease.
AB  - Exercise-associated oxygen desaturation in severe chronic obstructive pulmonary
      disease (COPD) remains a topic of unknown prognostic and clinical relevance and
      of unknown therapeutic importance. Furthermore, exercise limitation in these
      patients is due to multifactorial interaction of respiratory, cardiac,
      circulatory and 'peripheral' mechanisms. For the evaluation of the role of the
      oxygen-dependent mechanisms of exercise limitation we studied 14 stable patients
      with severe COPD (FEV1 32% pred., FEV1/VC 41%, thoracic gas volume of 180% pred.)
      and mean Pa O2 64 mm Hg by a stage 1 cycle exercise test during breathing room
      air (FiO2 0.21) and hyperoxic (FiO2 0.35) air. The measurements were performed by
      an open system using a low dead space valve (55 ml) measuring real-time breath by
      breath oxygen consumption (VO2) via a differential oxygen sensor, expired carbon
      dioxide (VCO2), ventilation (VE), oxygen pulse and oxygen saturation in both
      conditions. With FiO2 0.21 the mean exercise limitation was restricted to 37 (+/-
      14) W and the VO2 to 11.7 (+/- 2.4) ml/kg/min with peak oxygen desaturation of
      86.4 (+/- 3.2). With FiO2 0.35 the patients achieved a significant increase of
      workload to 55 (+/- 12.4) W and of VO2 to 14.9 (+/- 2.9) ml/kg/min. Despite the
      complete abolition of exercise desaturation by FIO2 0.35 the mean peak
      ventilation of 261/min (+/- 5.1) vs. 27 l/min (+/- 4.1) remained unaltered and
      therefore the restriction of the ventilatory pump limited the exercise ability.
      The effects of FiO2 0.35 occurred in these patients at submaximum exercise and
      may be related to reduction of ventilatory cost of energy and delayed onset of
      metabolic acidosis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7800957
TI  - Increased 24-hour endothelin-1 urinary excretion in patients with chronic
      obstructive pulmonary disease.
AB  - Abnormalities in endothelin-1 (ET-1) pulmonary metabolism have been reported in
      patients with pulmonary hypertension, asthma and chronic obstructive pulmonary
      disease (COPD). In this study we have evaluated the 24-hour urinary excretion of
      ET-1 in COPD patients both during acute exacerbation and stable phase of the
      disease. ET-1 plasma and urinary levels were measured in 13 COPD patients on
      admission to the hospital for an acute exacerbation and at the recovery period.
      Ten healthy volunteers were also studied. Determination of plasma and 24-Hour
      urinary ET-1 levels were carried out with a radioimmunoassay test. Plasma ET-1
      levels in COPD patients were similar during exacerbation and recovery and were
      not significantly different from those in the healthy subjects. 24-hour urinary
      excretion of ET-1 was increased in COPD patients during acute exacerbation; it
      decreased during recovery, but remained elevated when compared to normal
      subjects. A negative correlation was found between arterial oxygen pressure and
      ET-1 excretion; no correlation was found between plasma and urinary ET-1 values.
      In conclusion, COPD patients excrete higher amounts of ET-1 compared to healthy
      subjects. Urinary ET-1 values are further increased during acute exacerbation of
      the disease.

PMID- 7800958
TI  - Neutrophil count and myeloperoxidase activity in Indian bidi smokers.
AB  - Myeloperoxidase (MPO) level and MPO scoring were estimated in Indian bidi smokers
      and compared with those in cigarette smokers and non-smokers. The values were
      higher in the neutrophils of 20 bidi smokers compared to 20 age-matched non
      smokers (p < 0.001). However, they were similar to those in 20 cigarette smokers.
      No correlation of MPO activity was observed with blood carboxyhaemoglobin levels
      and smoking indices except in bidi smokers. Total leucocyte count and total
      neutrophil counts were also higher in bidi and cigarette smokers. This increased
      MPO activity in the neutrophils of bidi and cigarette smokers may contribute to
      the greater risk of obstructive pulmonary disease.

PMID- 7800959
TI  - Breath sound intensity in patients with airway provocation challenge test
      positive by spirometry but negative for wheezing: a preliminary report.
AB  - Wheeze detection has been proposed as an indicator of bronchial responsiveness
      during airway provocation challenge (APC) test. However, there is evidence that
      wheeze may be occasionally absent in subjects whose APC is positive by
      spirometry. We tested the hypothesis that, in this case, inspiratory breath sound
      intensity (BSI) over the chest is noticeably decreased. Six patients (3
      asthmatics and 3 patients with atopic rhinitis) were selected, whose forced
      expiratory volume in 1 s (FEV1) fell by 20% or more at the end point of the
      challenge in the absence of concurrent wheezing. Lung sounds were recorded at the
      right posterior lung base and analysed by computer. Inspiratory BSI at the end
      point of the challenge was markedly decreased in all patients, a change almost
      completely reverted by the inhalation of 200 micrograms of salbutamol in all of
      them but one. These results support the view that BSI monitoring is potentially
      useful as an indicator of bronchoconstriction during bronchial provocation
      testing. However, further studies are necessary to confirm this hypothesis.

PMID- 7800960
TI  - Prognostic factors in pulmonary metastases from colorectal cancer.
AB  - Surgery represents the first-choice treatment to manage pulmonary metastases from
      colorectal cancer when the primary tumor has been controlled and there is no
      evidence of metastatic spreading to any other organ. In our experience on 13
      patients, we obtained a survival at 5 years of 23%. The average number of
      metastases resected was 2.9. The increase of carcinoembryonic antigen was the
      first clinical sign in 10 cases (76.9%, higher or equal to 5 ng/ml) that led to
      its discovery. The surgical technique most frequently used was wedge resection
      and/or atypical segmentectomy. Intraoperative mortality was zero and morbidity
      low (15.3%).

PMID- 7800961
TI  - Value of ELISA using A60 antigen in the serodiagnosis of tuberculosis.
AB  - This study was set in a general, university hospital in the Canary Islands, with
      the objective to evaluate an enzyme-linked immunosorbent assay (ELISA) using A60
      in the serodiagnosis of tuberculosis. IgG antibody to A60 was determined in 205
      patients with active disease [149 culture-positive patients with pulmonary
      tuberculosis (positive sputum smear 94, negative sputum smear 55) and 56 patients
      with extrapulmonary tuberculosis], 20 patients with inactive disease, 22 patients
      with lepromatous leprosy, and 51 controls. The mean levels of anti-A60 antibodies
      were significantly higher in patients with active disease as compared with
      controls or patients with inactive disease. Differences were also found between
      tuberculous patients with pulmonary and extrapulmonary disease. In patients with
      pulmonary disease, significant differences were detected between smear-positive
      and smear-negative patients. The overall sensitivity of the test (cutoff 240
      ELISA units) was 52.2%. The highest sensitivity was found among smear-positive
      patients with pulmonary tuberculosis (67%) and the lowest among those with
      extrapulmonary tuberculosis (32.1%). We conclude that ELISA for the measurement
      of IgG antibody to Mycobacterium tuberculosis antigen A60 could be of interest,
      specially in smear-negative cases and extrapulmonary tuberculosis.

PMID- 7800962
TI  - Severe bronchial asthma improved on bamifylline. Case report and review.
AB  - We describe a 25-year-old patient with severe bronchial asthma, which was
      difficult to treat with oral theophylline. Bamifylline, a xanthine derivative,
      clearly improved the clinical signs, symptoms and lung function. We critically
      review the literature on bamifylline.

PMID- 7800963
TI  - A rare manifestation of von Recklinghausen neurofibromatosis: advanced
      neurofibromatous infiltration in lung of a HIV-positive patient.
AB  - This is a report of a 28-year-old HIV+ man with extensive involvement of lungs,
      spinal roots and peripheral nerves by neurofibromatosis von Recklinghausen. Huge
      masses (neurofibromas) ventral of the spine, which already infiltrated into the
      foramina intervertebralia, could be located by magnetic resonance imaging and
      high resolution computer tomography. Strikingly, most biopsies taken by
      bronchoscopy of the bronchial wall from various parts of the airways revealed
      extended infiltration by neurofibromas in submucosal areas, but no malignant
      tissue components. In addition, HIV infection with low CD4/CD8 ratio (0.1) and
      low CD4+ cells (160/microliters) was found.

PMID- 7800964
TI  - Idiopathic pulmonary-renal syndrome with antiproteinase 3 antibodies.
AB  - In this report, we describe a patient who developed acute renal failure and fatal
      pulmonary hemorrhage. Autopsy examination revealed pauci-immune necrotizing
      glomerulonephritis and pauci-immune hemorrhagic alveolar capillaritis. No
      evidence of granulomatous inflammation or vasculitis other than capillaritis was
      found in either lungs or kidneys. In addition, histopathologic examination of the
      upper respiratory tract, liver, spleen, digestive tract, and skeletal muscle was
      completely normal. The patient's serum sample disclosed antiproteinase 3
      antibodies with an immunofluorescence titer of 1:1,600. Although there have been
      reports of patients with pulmonary-renal syndrome in association with
      antiproteinase 3 antibodies in the absence of a well-known vasculitic disease, we
      have not so far seen a case documented by a detailed autopsy study such as is
      presented here. In view of our findings and those of some other reports on this
      clinicopathologic condition, we suggest that this might represent a distinct form
      of vasculitis with exclusive capillary involvement.

PMID- 7800965
TI  - Pleural effusion in yellow nail syndrome: chemical pleurodesis and its outcome.
AB  - Two cases of yellow nail syndrome (a triad of yellow dystrophic nails, chronic
      lymphedema and pleural effusion) are described which demonstrate long-term
      control of recurrent pleural effusions by tetracycline pleurodesis. Neither
      patient developed problems as a result of the procedure enabling us to conclude
      that tetracycline pleurodesis is effective in managing reaccumulating pleural
      fluid in yellow nail syndrome and may avoid loss of lung function due to pleural
      peel.

PMID- 7800966
TI  - Risk of infectious diseases in children attending different types of day-care
      setting. Epicreche Research Group.
AB  - This population-based prospective cohort study compared the risk of recurrent
      infections in children attending family day care (< or = 3 children per family),
      small (10-20 children) day-care centers (DCCs), and large (> or = 40 children)
      DCCs. The parents of a total of 1,242 children participated in the study (97% of
      the families initially contacted). An infectious episode was defined as the acute
      occurrence of a new symptom lasting for at least 48 h and resulting in specific
      treatment. Two episodes were counted as such only if they were separated by a
      symptom-free week. Surveillance was under the responsibility of a nursing
      director and was similar for all three types of DCCs. During the 8.5-month follow
      up period, 3,639 infectious episodes were recorded. Compared to those in family
      day-care, children attending small DCCs presented a higher risk for > or = 6
      total infectious episodes [odds ratio (OR) = 2.4; 95% confidence interval (CI) =
      1.6-3.7]; > or = 5 upper respiratory tract infections (OR = 2.2; 95% CI = 1.4
      3.4); > or = 2 episodes of otitis media (OR = 2.6; 95% CI = 1.0-2.6); > or = 2
      episodes of conjunctivitis (OR = 4.1; 95% CI = 2.1-8.2); and > or = 2 episodes of
      croup (OR = 4.1; 95% CI = 1.6-10.9). The risk for children attending large DCCs
      was intermediate between those in family day care and those in small
      DCCs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7800967
TI  - OM-85 BV: primary versus secondary prevention.
AB  - Recurrent upper respiratory tract infections in children have an important
      socioeconomic impact, with consequences on both the quality of life of the
      children, the possible medical sequelae and the inherent direct and indirect
      costs. The possibility to prevent these infections is limited in the absence of
      specific vaccines against microorganisms responsible for most of the respiratory
      tract infections (i.e. respiratory syncitial virus, adenovirus, rhinovirus).
      Immunoactive bacterial extracts that stimulate the nonspecific component of the
      immune system may protect against a large variety of microorganisms that enter
      the body by the oral and respiratory pathway; they may, therefore, play an
      important role with regard to this preventive action. OM-85 BV is an IBE that has
      been used in children who suffer from repeated infections to prevent the
      occurrence of new episodes (secondary prevention). In this condition, the drug
      has been shown to be effective in protecting children against recurrent airway
      infections. Its use as a primary preventive agent to prevent the development of
      repeated infections in children attending day-care centers (a very high-risk
      environment for repeated infections), however, did not show a similar efficacy.
      The risk of having > or = 4 episodes of upper respiratory tract infections over a
      period of 7.5 months was 26.7% in the verum group and 33.8% in the placebo group
      (relative risk 0.79, confidence interval 0.59-1.06]. In an exploratory analysis
      concentrating on the 3-month treatment period, however, a 48% reduction of the
      risk of presenting > or = 3 episodes was observed. Furthermore, this exploratory
      analysis showed a strong correlation between drug efficacy and age of the
      children.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7800968
TI  - Epidemiology of viral infections and evaluation of the potential benefit of OM-85
      BV on the virologic status of children attending day-care centers.
AB  - Viral investigations were performed during 4 winter seasons (88/89, 89/90, 92/93,
      93/94) in children attending day-care centers (DCCs) in the Rhone Departement in
      eastern France. Over the total observation period of 4 winter seasons, 780
      children were screened with a nasal swab for the presence of viruses. Of those,
      230 (29.5%) had a positive viral culture. The viruses identified were respiratory
      syncytial virus (RSV), influenza A and B virus, parainfluenza virus, coronavirus,
      rhinovirus, adenovirus and enterovirus. During that time, 83 epidemic events in
      47 DCC were recorded. A particular virus was judged to be causally related to an
      epidemic if the identical virus was isolated in > or = 3 children during the same
      outbreak of respiratory diseases. Thus, in 51 cases (61.4%) of all epidemics, the
      following viruses were responsible for an epidemic: RSV (n = 23), coronavirus (n
      = 10) (only during the season of 1993-1994), influenza A virus (n = 6),
      rhinovirus (n = 4), enterovirus (n = 4), adenovirus (n = 3) and parainfluenza
      virus (n = 1). Except for the somewhat surprising accumulation of coronavirus
      epidemics during the winter of 1993-1994, there were only minor seasonal
      variations from one year to another. As expected, RSV accounted for about one
      third of all respiratory tract infections in children attending DCCs and was
      therefore the most important single causative agent. These results are compared
      with data from children who did not attend a DCC and were cared for in a private
      practice.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7800969
TI  - Stimulation of immunoprotective mechanisms by OM-85 BV. A review of results from
      in vivo and in vitro studies.
AB  - OM-85 BV, an immunomodulating preparation containing extracts from eight commonly
      pathogenic bacterial species, has been used with success as an oral adjuvant in
      the prevention of respiratory tract infections. Results from in vitro and in vivo
      experiments suggest various mechanisms that can underlie this beneficial effect.
      Thus, exposure of murine macrophages in vitro to OM-85 BV led to stimulation of
      biochemical and functional parameters associated with the disposal of
      microorganisms and tumor cells. Similarly, blood-derived human phagocytes were
      stimulated to express adhesion molecules (LFA-1, MAC-1, p150,95, ICAM-1), to
      synthesize TNF-alpha and IL-2, and to develop a natural killer activity. These in
      vitro functions are reflected in the activation of immunological processes in
      vivo following administration of OM-85 BV per os. Oral treatment of mice and
      rabbits increased the capacity of the animals to clear bacteria from the blood,
      an effect that could be ascribed to enhanced functional activity of
      polymorphonuclear leukocytes. Administration of OM-85 BV per os also led to
      enhanced salivary IgA levels in man, and in gut and lung secretions in animals.
      Stimulation of migration and the beneficial effects of OM-85 BV correlated with
      phagocytosis-induced superoxide production in human bronchoalveolar lavage cells
      from orally treated individuals. Finally, injection of OM-85 BV was shown to
      enhance recovery from irradiation in animals, presumably by improving hemopoietic
      recovery. These findings indicate that OM-85 BV is capable of stimulating both
      cellular and humoral components of the immune response.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7800970
TI  - Cancer critical care: past, present, and future.
AB  - Utilization of critical care interventions for cancer patients has increased
      because of new hopes for cure or long-term remission, increased ability to treat
      certain complications, and consumer demand. Cancer therapies are more aggressive
      causing increased organ toxicity, prolonged aplasia, and a variety of
      complications that may be life threatening. Public awareness and knowledge that
      cancer no longer means death has permitted cancer patients to partake of critical
      care technology. The nurse plays a key role in anticipating and predicting
      critical complications.

PMID- 7800971
TI  - Ethical dilemmas in the delivery of intensive care to critically ill oncology
      patients.
AB  - Caring for the critically ill oncology patient presents ethical dilemmas with
      which the critical care oncology nurse may need assistance. Understanding how
      values can be in conflict encourages exploration of alternatives. As health care
      professionals, one of our missions is to learn to make decisions using current
      knowledge about clinical problems and expected outcomes, value systems that
      affect our decisions, and systematic approaches to problem solving. Our challenge
      is well-defined.

PMID- 7800972
TI  - Heart, lung, and endocrine complications of solid tumors.
AB  - Many cancers and complications of cancer treatment may cause major critical care
      problems. Cardiopulmonary complications include pericardial effusion, cardiac
      tamponade, superior vena cava syndrome, pleural effusion, pulmonary embolism,
      radiation pneumonitis, and toxicities related to chemotherapy. Syndrome of
      inappropriate antidiuretic hormone (SIADH), Cushing's disease, and hypercalcemia
      are common endocrine complications associated with solid tumors. Astute nursing
      assessment plays an important role in preventing or reducing morbidity related to
      these complications.

PMID- 7800973
TI  - Selected complications in the patient with cancer: spinal cord compression,
      malignant bowel obstruction, malignant ascites, and gastrointestinal bleeding.
AB  - The growth rate of a tumor, patterns of tumor growth and metastatic spread, and
      toxicity of therapy contribute to the type and severity of complications. Four
      common critical care complications resulting from compressive and invasive
      properties of tumors include spinal cord compression, malignant bowel
      obstruction, malignant ascites, and gastrointestinal bleeding. Knowledge of the
      clinical presentations of each of these complications provides a foundation for
      nursing assessment.

PMID- 7800974
TI  - Critical care issues in the patient with hematologic malignancy.
AB  - Patients with lymphomas, multiple myeloma, and leukemia are often at risk for
      life-threatening complications. Complications include viral infections (eg,
      herpes zoster, herpes simplex, cytomegalovirus) and hemolytic anemia, which are
      related to the hematologic origin of the malignancy. Life-threatening disorders
      related to amount of tumor burden are leukostasis and hyperviscosity.
      Complications related to therapy include pulmonary capillary leak syndrome and
      tumor lysis syndrome. Good assessment skills assist in early identification of
      individuals at risk and initiation of preventive measures.

PMID- 7800975
TI  - Creating critical care oncology beds.
AB  - The emergence of specialized oncology practices such as bone marrow
      transplantation has resulted in a higher incidence of critical complications and
      complex needs, which has led many oncology units to develop new strategies to
      care for the patients in the oncology unit. Designated oncology intensive care
      unit (ICU) beds and a dedicated trained staff is one method of delivery; other
      institutions transfer patients to existing ICUs, and some have equipped the
      entire oncology unit for critical care interventions. It is necessary to evaluate
      key issues when providing critical care to patients with cancer.

PMID- 7800976
TI  - CT-guided stereotactic biopsy of nonenhancing brain lesions.
AB  - The majority of computer tomography stereotactic biopsy lesions enhance after
      administration of intravenous contrast, whereas patients with nonenhancing
      lesions are often followed conservatively or undergo craniotomies. There are few
      studies showing the effectiveness of stereotactic biopsies of nonenhancing
      cerebral lesions. Stereotactic biopsies were performed on 19 patients with
      lesions that did not enhance on CT after intravenous contrast. Pathological
      diagnoses were made in 90% (17/19) of patients. Four HIV-positive patients had
      progressive multifocal leukoencephalopathy, 11 patients had gliomas (4
      astrocytomas, 6 anaplastic astrocytomas, and 1 ganglioma), 1 had multiple
      sclerosis, and 1 had herpes encephalitis. In 2 patients multiple biopsies
      revealed only gliosis. There was no morbidity or mortality. Stereotactic biopsies
      for nonenhancing brain lesions have a high diagnostic yield and can favorably
      alter the treatment course.

PMID- 7800977
TI  - CT and pathological study on radiofrequency-induced lesion in cat thalamus.
AB  - In order to observe the postoperative focal changes caused by radiofrequency
      lesions in the ventrolateral nucleus of the thalamus in stereotactic treatment of
      Parkinson's disease, similar lesions were produced in cat. The CT features and
      their correlative pathologic changes at different intervals were divided into
      three types, four stages and three zones. The degree of susceptibility of nervous
      tissue to radiofrequency, repair characteristics and the mechanism of CT
      enhancement are discussed in light of the pathologic changes.

PMID- 7800978
TI  - Analysis of parameters for epidural spinal cord stimulation. 1. Perception and
      tolerance thresholds resulting from 1,100 combinations.
AB  - A computerized statistical analysis of 1,100 quadripolar electrode combinations
      used in epidural spinal cord stimulation therapy for the management of pain was
      carried out to investigate perception and tolerance thresholds. This analysis
      showed that the thresholds are higher at high-cervical, mid-cervical, mid
      thoracic and low-thoracic spinal levels. It is also higher for the combinations
      with contacts located in the midline than those implanted laterally. As the
      contact separation increases, the perception and tolerance thresholds increase in
      bipolar combinations. Unipolar combinations have the lowest thresholds.

PMID- 7800979
TI  - Analysis of parameters for epidural spinal cord stimulation. 2. Usage ranges
      resulting from 3,000 combinations.
AB  - A computerized statistical analysis of 3,000 implanted electrode (multi-contact,
      quadripolar) combinations for epidural spinal cord stimulation therapy for the
      management of pain was carried out in three groups: spinal levels (20 different
      levels, C2-L2), spinal placement (midline and lateral) and contact separation
      (unipolar, bipolar with a separation of 10, 20 and 30 mm) to investigate the
      clinically required usage ranges (difference between the perception threshold and
      tolerance threshold). The usage range is relatively higher at midthoracic levels
      (T4-T10), and for the combinations located in midline. As the contact separation
      increases, the usage range increases in bipolar combinations. The usage range of
      unipolar combinations is higher than that of bipolar combinations with 10 and 20
      mm separation, and is less than that of bipolar combinations having a separation
      of 30 mm.

PMID- 7800980
TI  - Analysis of parameters for epidural spinal cord stimulation. 3. Topographical
      distribution of paresthesiae--a preliminary analysis of 266 combinations with
      contacts implanted in the midcervical and midthoracic vertebral levels.
AB  - As a part of the systematic analysis of parameters involved in electrical
      epidural spinal cord stimulation therapy, distribution of paresthesiae in
      accordance with the position of contacts, as related to midline and vertebral
      level of contacts, was investigated. A preliminary analysis performed for 266
      combinations having contacts implanted in the midcervical and low-thoracic
      vertebral levels showed that the topographical spread of the paresthesiae did not
      always cover the classical dermatomes. Significant paresthesiae spread was found
      as follows: C4-midline, unipolar combinations; the hand, forearm and upperarm,
      bipolar combinations; the hand, forearm; C4-lateral, unipolar combinations: the
      anterior shoulder, forearm, upper arm and hand, bipolar combinations: the hand,
      forearm and upper arm; T10-midline, unipolar combinations: the anterior and
      posterior of thigh, leg, knee, ankle and foot, bipolar combinations: the anterior
      and posterior thigh, leg, knee and foot; T10-lateral, unipolar combinations: the
      abdomen, anterior leg, knee and anterior thigh, bipolar combinations: the
      anterior thigh, anterior leg, knee and foot. This preliminary analysis suggests
      that more detailed studies would be worthwhile in the investigation of sensory
      responses to electrical stimulation of the spinal cord with epidural electrodes.
      Findings from such investigations could also be useful to extend our present
      anatomical knowledge of central and peripheral sensory neural structures.

PMID- 7800981
TI  - [Vitamin E and atherosclerosis].

PMID- 7800982
TI  - [CD8 hyperlymphocytosis syndrome and human immunodeficiency virus infection: 5
      cases].
AB  - A retrospective study on 202 consecutive patients with HIV infection was
      reviewed. A particular syndrome with blood CD8 lymphocytosis > 1 500/mm3,
      associated with a diffuse lymphocytic infiltrate histologically proved in the
      tissue of different organs was present in five patients. Clinical findings were
      variable, depending on the location of visceral infiltrate by activated,
      polyclonal lymphocytes of CD8 phenotype: interstitial pneumonia (n = 3), parotid
      gland enlargement with sicca syndrome (n = 2), pseudo-tumoral splenomegaly (n =
      1), peripheral neuropathy (n = 1), superficial generalized lymphadenopathy (n =
      5). This syndrome occurred early during HIV infection. All patients had a blood
      CD4 lymphocyte count > 200/mm3. This disorder is a host immune response,
      sometimes associated with the presence of some HLA antigens: HLA-DR5 or HLA A1 B8
      DR3. Whether this immune response is specific or not, whether outcome of HIV
      infection depends on hyper CD8 lymphocytosis remains to be proved.

PMID- 7800983
TI  - [Polyneuropathies and myelopathy associated with a circulating anticoagulant.
      Apropos of 4 cases].
AB  - During one year from July 1992 to July 1993, we performed usual hemostasis tests
      in a population or 3,700 patients. We found 12 patients with a lupus like
      anticoagulant (incidence: 1/1,000). Among these 12, four had unexplained
      polyneuropathy or myelopathy. Lupus like anticoagulant was either isolated (two
      cases), either associated with thrombosis (two cases). We report these four cases
      and we discuss the causal or uncasual nature of this association.

PMID- 7800984
TI  - [Vitamin E, antioxidants and atherosclerosis].
AB  - Atherosclerosis is a process in which lipid and factors are mixed. When LDL are
      oxydized, they are catabolized by the macrophage's pathway, leading to foam cells
      which constitute the fatty streak, the earliest lesion in atherogenesis, and they
      have cytotoxic, chemotactic effects. Many protective devices against free
      radicals and oxydation mechanisms exist, particularly antioxydant vitamins and
      other natural dietary antioxydants. After a brief recall of their mechanisms,
      epidemiological, experimental and clinical data are reviewed. To day it seems
      necessary to take into consideration these factors in prevention and therapeutic
      of atherosclerosis and dylipidaemia. Many inquiries keep going, particularly
      about susceptible of LDL to oxydation. One is waiting for intervention surveys in
      order to conclude about nutritional and medical treatments.

PMID- 7800985
TI  - [CA 15-3 and breast cancer].
AB  - The precise clinical value of CA 15-3 antigen has yet to be determined. With no
      role in screening for early breast cancer and, even if CA 15-3 seems to be
      correlated with bulky initial tumor burden, it appears to have no independent
      prognostic value. The clinical interest of CA 15-3 remains the early detection of
      the first recurrence. In this regard, more than 75% of first recurrences (all
      sites included) are associated with a significant rise in CA 15-3 levels, with a
      particular sensitivity for bone, liver, and lung metastases but which appears
      lower for locoregional recurrences. More sensitive and specific than CEA, and
      this whatever the site of recurrence, the rise of CA 15-3 may precede the
      clinically or radiologically diagnostic of recurrence by a mean lead time from 6
      to 9 months. Furthermore CA 15-3 is a reliable marker for clinical course and
      seems to be of potential interest in monitoring disease follow-up during therapy.
      In the situation of a clinically isolated elevation of CA 15-3, which
      investigations, if any, have to be done?, and if negative must do we initiate a
      treatment for a "biological recurrence"? All these questions remain still opened,
      and today on consensual attitude can be recommended. In this issue, only results
      of well-designed prospective trials could help us to determine more rationally,
      an optimal diagnostic and therapeutic strategy.

PMID- 7800986
TI  - [Recurrent metabolic encephalopathy, self-administered gastric lavage and
      Munchausen syndrome].
AB  - A case report of recurrent metabolic encephalopathy with disorders of hydro
      electrolytic balance, predominantly severe hypochloremic alkalosis, resulting
      from self-induced vomiting and self-administered gastric tubage and lavage.
      Munchausen syndrome was diagnosed. Some established characteristics of this
      syndrome as well as some atypical features concerning patient-doctor relationship
      and natural history are discussed.

PMID- 7800987
TI  - [Yellow nail syndrome. Apropos of 2 cases. Review of the literature].
AB  - The yellow nail syndrome is a clinical syndrome without specific biological
      parameters. It is characterized by the following threesome of symptoms: nail
      abnormalities, primary lymphedema, and pleuropulmonary manifestations. In most
      cases lymphography shows abnormalities of the lymphatic vessels and spirometry
      shows a restrictive defect and rarely obstructive disorders. Pathogenesis of this
      syndrome is still unknown. It is, however, remarkable that the yellow nail
      syndrome may occur in association with other diseases, the most frequent of which
      are cancer affections and immune disorders. We report two cases of the yellow
      nail syndrome which were associated with cancer (neoplasm of the larynx and
      breast).

PMID- 7800988
TI  - [Acute myelitis in the post-eruptive phase of measles].
AB  - An acute isolated myelitis occurring at the post-eruptive phase of measles is
      reported. This unusual complication of measles has a favourable outcome in the
      most of cases. An immunological mechanism, identical to this responsible of
      perivenous encephalitis seems to be involved.

PMID- 7800989
TI  - [Paraneoplastic edema syndromes in acute myelomonocytic leukemia: role of TNF
      alpha and IL-6?].
AB  - We report the case of a 56 year-old man in remission of a Hodgkin's disease who
      had an acute myelomonocytic leukemia with major edemas. Chemotherapy temporarily
      allowed a concomitant regression of edemas, hyperleukocytosis and tumor necrosis
      factor and interleukin-6 levels which were initially elevated. We discuss the
      role of these two cytokines in endothelium permeability disorders.

PMID- 7800991
TI  - [History of internal medicine].
AB  - The concept of Internal Medicine was introduced recently and stems from the
      Internal Pathology which dates back to Antiquity. This concept spread out during
      the XIXth century with the concomitant progress of clinical science and heurism
      within a global and humanistic medicine. In France, Internal Medicine was not
      recognized until 1966. The criteria of eligibility for certification in this
      specialty were issued in 1970. The Syndicat National des Medecins Specialistes de
      Medecine Interne, the Societe Nationale Francaise de Medecine Interne and the
      diploma of certification in Internal Medicine were respectively created in 1975,
      1979, 1984. The field of interest of Internal Medicine is wide and ambiguous. It
      includes a specific hard core and less specific allocations that encroach on
      "organ" specialties. French internist practitioners are not numerous and most of
      them are practising in hospitals. Internal Medicine is highly regarded in Anglo
      Saxon countries and in Germany. In the European Community, the future of this
      medical specialty depends on the success of the harmonization of training
      programs and the development of medical students exchange. There is currently a
      controversy about the recognition of Internal Medicine as a full specialty. To
      bring out this specialty, French internists should benefit from reforms at
      several levels: university, hospital and French health service contract.

PMID- 7800990
TI  - [Treatment of Crohn disease in adults].
AB  - Corticosteroids are an efficient treatment for active Crohn's disease. The
      treatment has to be undertaken with a daily intake equivalent to 1 mg/kg per day
      of prednisolone for a 3 to 7 week period. Immunosuppressive agents are indicated
      in case of corticodependency or in case of large intestinal resection. Artificial
      nutrition (enteral or parenteral) is proposed in corticoresistant forms, and is
      usually followed by an immunosuppressive therapy. Surgical management is reserved
      for complications, including resistance to all medical therapy. Surgical
      resection has to be limited in order to avoid a short bowel syndrome. Surgery
      should not be considered as the ideal therapy as it has been demonstrated that
      recurrence after surgery increases at distance. 5-aminosalycilates compounds are
      an alternative therapy in mild attacks. Mesalazine may reduce the recurrence and
      could be considered as a possible maintenance treatment.

PMID- 7800992
TI  - [Association of familial polycystic kidney and primary hyperaldosteronism].

PMID- 7800993
TI  - [Acute rhabdomyolysis caused by fenoverine].

PMID- 7800994
TI  - [Theophylline overdose following a treatment with viloxazine].

PMID- 7800995
TI  - [How I treat... a first episode of depression].

PMID- 7800996
TI  - [Bronchodilator treatment of patients with COPD (1994)].

PMID- 7800997
TI  - [Asthmatic syndrome in infants: from diagnosis to management].

PMID- 7800998
TI  - [Neurological manifestations of Borrelia burgdorferi infection (Lyme disease)].

PMID- 7800999
TI  - [Leiomyoma, a painful cutaneous tumor].

PMID- 7801000
TI  - [Anatomoclinical conference: apropos of 2 cases of bacterial meningitis].

PMID- 7801001
TI  - [Liver, enzymes and drugs. Unexpected etymologies (1)].

PMID- 7801002
TI  - [The death of Madame].

PMID- 7801003
TI  - [What is your diagnosis? Ureteral obstruction in inflammatory abdominal aortic
      aneurysm].

PMID- 7801004
TI  - [Body image, weight and eating behavior in adolescents].
AB  - The aim of the study was to assess the incidence of abnormal eating behaviour in
      relation to age, sex, and body awareness as well as to find potential access to
      the prevention of eating disorders. The study population was taken from 203
      female and 153 male college students aged 14 to 19 years. The method chosen was a
      self-report questionnaire asking for assessment of current body image and ideal
      body image by body size silhouettes, dietary habits, methods of weight control
      and symptoms of eating disorder. Measurements of height and weight were also
      included. RESULTS: Among girls, 63% are satisfied with their body shape, in
      contrast to 93% of the boys. The current body shape matches the ideal body image
      in 49% of the girls and in 69% of the boys. In two thirds of the female students
      the ideal body image corresponds to a slightly underweight silhouette, whereas in
      four fifth of the male students it corresponds to a normal-weight silhouette. A
      majority of girls (53% vs. 13% boys) is afraid of gaining weight. Four times as
      many girls use a variety of methods to lose weight. There were no sex differences
      concerning the regularity of meal intake. Only 13% of all students took all three
      main meals daily. Eating habits were significantly worse with higher body-mass
      index. A high risk for the presence of an eating disorder was seen exclusively in
      girls (4%), whereas the majority of boys (99%) are represented in the low-risk
      group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7801005
TI  - [How do we define inflammation?].
AB  - Nowadays inflammation is commonly defined as a defensive reaction involving the
      immune system. This paper clarifies the historical roots of this definition. The
      Russian embryologist Metchnikoff made--100 years ago--the initial observations on
      phagocytosis that provided a definition of inflammation based on a cellular
      theory of immunity. Following the many attacks by those who favored the view that
      immunity was based upon humoral mechanisms, Bordet argued that Metchnikoff's
      cellular theory of inflammation could be reconciled with the theory of humoral
      immunity. This study helps the modern reader to grasp the theoretical assumptions
      supporting our concept of inflammation.

PMID- 7801006
TI  - [Vomiting, upper abdominal pain and sepsis].
AB  - A 78-year-old man was admitted to a surgical emergency room because of an acute
      abdomen. He had vomited violently four times shortly after a meal. This episode
      was followed by severe upper abdominal and thoracic pain, radiating to the back.
      Clinical evaluation revealed epigastric peritoneal signs and a soft lower
      abdomen. Emergency laparotomy disclosed peritoneal adhesions, a distended stomach
      and numerous diverticula of the small intestine. Neither a perforation nor
      inflammatory signs were noted. A dramatic accentuation of the pain occurred,
      followed by the clinical picture of septic-toxic shock. On a chest X-ray, liquid
      was noted in the left pleural cavity. On occasion of a puncture, this liquid was
      found to be malodorous and bloody. Cultures yielded Vibrio vulmificus,
      streptococcus viridans as well as proteus and klebsiella species. The patient
      succumbed to multiorgan failure on the third day of hospitalization. The autopsy
      disclosed a recent rupture of the esophagus (Boerhaave syndrome) with purulent
      peri-esophagitis and mediastinitis as well as fibrinopurulent left-sided
      pleuritis.

PMID- 7801007
TI  - [Abdominal pain, weight loss, tarry stools].
AB  - A 65-year-old man had abdominal pain and night sweat for several weeks. He had
      lost weight and also reported black stools. Anemia of iron deficiency was found
      in laboratory tests. Further investigation revealed a stenosing process in the
      small intestine as source of bleeding. High grade non-Hodgkins' lymphoma was
      diagnosed histologically in the resected bowel segment and the mesenteric lymph
      nodes. Further staging did not reveal further manifestations of lymphoma.
      Polychemotherapy and subsequent irradiation were administered.

PMID- 7801008
TI  - [A case from practice (312). Chronic active hepatitis B--nonresponder to
      interferon therapy].

PMID- 7801009
TI  - [Current techniques in pneumonology/pulmonary infections].

PMID- 7801011
TI  - [Pneumonia in clinical practice: diagnosis and therapy].
AB  - Outpatients with pneumonia are usually treated empirically. Therefore, the
      knowledge of the most important causative agents is a prerequisite for the
      'educated guess'. With a broad microbiological evaluation, the etiology of a
      pneumonia can be detected in only half of the cases. In outpatients, 30% of the
      causative agents are viruses, 45% 'atypical bacteria' such as Mycoplasma sp. and
      Chlamydia pneumoniae, and 25% pneumococci and Hemophilus. In hospitalized
      patients, pneumococci and Hemophilus cause 60%, and 'atypical bacteria' only 25%
      of the community acquired pneumonias. The most relevant microbiological
      examination in outpatients is the Gram stain of the sputum. The sputum culture is
      seldom useful and sometimes even misleading, especially if the result is not
      interpreted in connection with the Gram stain. The most appropriate treatment of
      outpatients without underlying disease is a macrolide. In patients with chronic
      bronchitis, alcoholism or preceding influenza infection, amoxicillin/clavulanic
      acid or a new oral cephalosporin is the best choice. The detection of risk
      factors for fatal outcome is important for the decision to admit the patient to a
      hospital.

PMID- 7801010
TI  - [Pulmonary infectious complications in HIV disease].
AB  - The spectrum of HIV-related pulmonary infectious and noninfectious complications
      has enlarged considerably during the past years. Because clinical and
      radiological presentation is generally nonspecific the diagnostic workup should
      be straightforward. The diagnosis of the still most important complication,
      pneumocystis carinii pneumonia, can often be achieved by examination of sputum.
      If this is not possible, the next diagnostic step is bronchoalveolar lavage. Due
      to rapid diagnosis and treatment as well as prophylactic measures the prognosis
      of these HIV-related complications has improved significantly.

PMID- 7801012
TI  - [Interventional bronchoscopy].
AB  - The field of bronchoscopy has considerably expanded in recent years. The rigid
      and flexible bronchoscope are both used for diagnostic and increasingly for
      therapeutic procedures; for the therapeutic procedures the term 'interventional
      bronchoscopy' has been coined. Apart from the more traditional indications for
      interventional bronchoscopies, such as aspiration of secretions and removal of
      foreign bodies, the treatment of inoperable stenoses of the central airways-
      benign or malignant--has moved to the center stage of interventional endoscopies.
      This review focuses on the technique and indication of the following procedures:
      bronchial toilette, foreign body removal, dilatation, diathermy, cryotherapy,
      photodynamic therapy, laser resection, brachytherapy and the insertion of stents
      (endoprostheses).

PMID- 7801013
TI  - [The treatment of obstructive sleep apnea].
AB  - Diagnosis of obstructive sleep apnea syndrome may be suspected clinically,
      screened for by oximetry and proven by polysomnography. A sufficient number of
      centers performing polysomnography and providing appropriate treatment is
      available today in Switzerland. The patient does not need to be admitted to a
      university center since nearly all high altitude clinics with pneumonologic
      orientation are equipped to diagnose and treat patients with obstructive sleep
      apnea syndrome. The treatment of choice is nocturnal CPAP-therapy which is
      simple, poor in complications and well tolerated. Regular follow-up by cantonal
      leagues for pulmonary diseases, practising pneumologists and pneumonologic
      centers are, however, necessary.

PMID- 7801014
TI  - [Mechanical home ventilation: indications for and application of nocturnal
      ventilation using nasal masks in chronic hypoventilation].
AB  - Mechanical ventilation at home has formerly been used mainly to treat respiratory
      failure after poliomyelitis. Nowadays this method has been refined such that
      insufflation is no longer necessary through a tracheostoma but via either a
      specially molded or a customized nose-mask. Ventilation occurs mainly at night
      for periodic relief of the respiratory musculature. Indications are restrictive
      ventilatory deficits such as kyphoscoliosis or the postthoracoplasty syndrome,
      slowly progressing neuromuscular diseases and sometimes traumatic tetraparesis.
      Evaluation and instruction of the patient take place in a pneumologic center in
      close cooperation with the cantonal leagues for pulmonary diseases and the family
      physician. Accordingly a collaboration of all social and medical institutions as
      well as the participation of close relatives are a prerequisite for a successful
      mechanical ventilation at home.

PMID- 7801015
TI  - [The effect of endogenous opioids in blood pressure regulation and arterial
      hypertension].
AB  - There are numerous hints to the participation of endogenous opioids in the tonic
      regulation of blood pressure and in pathogenesis and maintenance of essential
      hypertension. Endogenous mu- and delta-receptor agonists of the central nervous
      system seem to regulate long-term control of the sympathetic tone in essential
      hypertension. In the initial stage of hypertension, altered responses to opioid
      agonists and antagonists could be demonstrated in young spontaneously
      hypertensive rats. In young, but not in old hypertensive patients alterations of
      plasma concentrations of endogenous opioids were found. Reactivity and
      reagibility of blood pressure seem to be regulated rather independently from
      endogenous opioids, but they may modulate the influence of psychosocial stress on
      blood pressure.

PMID- 7801016
TI  - [Differential diagnosis of insulin- and noninsulin-dependent diabetes mellitus-
      are there therapeutic implications?].
AB  - Although insulin-dependent and non insulin-dependent diabetes mellitus have a
      different pathogenesis, they are often indistinguishable by clinical and
      laboratory parameters. Complications in connection with diabetic micro- and
      macroangiopathy (retino-, nephro- and polyneuropathy, cardiovascular risks) are
      similar in both types of diabetes. Treatment is based on clinical presentation
      and routine laboratory tests, its goal is normoglycemia. The criteria for use of
      insulin are the same for all variants of diabetes. Control of associated
      cardiovascular risk factors is decisive. Diabetes is a clinical syndrome.

PMID- 7801017
TI  - [Well-cared-for illness?--from the early times of the social insurance system].
AB  - This paper examines the reaction of physicians to the inauguration of a system of
      social insurance at the beginning of the twentieth century in Germany. The
      writings of Erwin Liek--a spokesman of German physicians in this respect--show
      how social insurance, which was inextricably connected with a social and an
      economic crisis, had a negative influence on medicine: individual therapeutical
      relationship has been replaced by a bureaucratic dialogue which favours upholding
      a state of disease instead of promoting health. This study suggests that Liek's
      criticism bears some analogy with today's german criticism of the social
      insurance system.

PMID- 7801018
TI  - [Muscle ache and vision disorders in a South American immigrant to Switzerland].

PMID- 7801019
TI  - [Polyuria, polydipsia].
AB  - A 24 year old patient with epigastric pain, polyuria, polydipsia and
      hypercalcemia was admitted to the hospital. Besides the frequent causes of
      hypercalcemia such as primary hyperparathyroidism and malignancy-related
      hypercalcemia we had to consider sarcoidosis because of massive splenomegaly. The
      interstitial lung disease shown on x-ray films of the chest, the epithelioid
      granulomas in lung tissue and the increased ACE confirmed the diagnosis of
      sarcoidosis. Hypercalcemia is found in less than 5% of all cases with
      sarcoidosis. After treatment with steroids, diphosphonates and diuretics all
      symptoms and the hypercalcemia improved.

PMID- 7801020
TI  - [A case from practice (313). Liver abscess with Bacteroides fragilis sepsis-
      factitial hyperthyroidism--arterial hypertension--alcoholism].

PMID- 7801021
TI  - [Digestive symptomatology and psychiatric behavior. Internist's viewpoint].

PMID- 7801022
TI  - [Body image, nutritional behavior and dysfunction among Swiss adolescents: a
      national survey].

PMID- 7801024
TI  - [Emergency medical assistance: a global idea].

PMID- 7801023
TI  - [Echography of the hip in infants. Why absolute deference to Graf's criteria is
      necessary].

PMID- 7801025
TI  - [Computer alert and quality of care: application to the surveillance of hospital
      infections].
AB  - The Centre Informatique of Geneva University Hospital is developing, in the
      environment of its hospital information system, DIOGENE, a computerized alert
      system for surveillance of hospital infections. This hospital information system
      is based on an open distributed architecture and a relational database system,
      and covers many medical applications. This environment allows the development of
      alerts useful for detecting patients at risk. The alerts offer to clinicians a
      mean to control their efficacy in patient care. They are a new application of
      telematics for surveillance in clinical epidemiology, and are a tool for quality
      assurance. Two examples of alerts established for hospital infection control
      activities are presented. The first alert systematically detects all cases of
      patients colonized by or infected with methicillin-resistant Staphylococcus
      aureus (MRSA). The second alert helps to organize prospective surveillance of
      bloodstream infections in order to identify some risk factors for infection and
      propose preventive measures.

PMID- 7801026
TI  - [Concerning M. Jacques Salome's article: apropos of "Sects and their influence on
      adolescents'].

PMID- 7801027
TI  - [Logic of the anorexic person as opposed to that of her physicians].

PMID- 7801028
TI  - [The needs of the anorexic person].

PMID- 7801029
TI  - [The course of anorexia nervosa: apropos of a case].

PMID- 7801030
TI  - [Anorexia nervosa in boys].

PMID- 7801031
TI  - [Anorexia in the general hospital: from emergency to crisis].

PMID- 7801032
TI  - [Nutrition problems in early infancy: clinical and therapeutic aspects in child
      psychiatry].

PMID- 7801033
TI  - [Diagnosis and management of an adolescent with anorexia: practitioner's role].

PMID- 7801034
TI  - [Group treatment unit for hospitalized anorectic patients: between demand and
      need].

PMID- 7801035
TI  - [Neuropathology of 20 centenarians. I. Clinical data].
AB  - We report a clinical study of 20 patients aged more than 100 years, and deceased
      in Charles Foix Hospital, Ivry/Seine, France, where they had stayed for 10 days
      to 16 years (mean: 3.3 years, median: 4 years). Each of them was studied
      neuropathologically (the results of this study will be published later on). The
      case selection excluded only those patients whose neuropathological study could
      not be complete. The prevalence of sensorial deficits was high: 15/20 patients
      had deterioration of hearing, 8 of them were deaf; 14/20 patients had
      deterioration of sight, 4 of them were blind. Motor deficits were numerous: 15
      patients were not ambulatory. The patients were classified as demented or not,
      according to the criteria of the DSMIII R (American Psychiatric Association
      1987), on the basis of a retrospective evaluation of clinical records, and of an
      inquiry among the caring staff. Their mental status was also evaluated by the
      Global Deterioration Scale of Reisberg et al (1985). Five patients had been
      demented, four had been intellectually normal, and 11 had suffered from mild
      disturbances of memory or cognitive functions. This series was not representative
      of the general population of centenarians, but probably of those
      institutionalized in France. We observed a low proportion of demented patients
      despite the prevalence expected from epidemiological studies. This is difficult
      to interpret. The low proportion of dementia in this small sample is not due to
      the short duration of the course of diseases responsible for dementia.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7801036
TI  - [Acute ischemic spinal cord disease. Spinal cord infarction. A clinical study and
      MRI in 8 cases].
AB  - Acute spinal cord infarction (ASCI) occurs infrequently and may have diverse
      causes. The diagnosis of ASCI, and particularly of an anterior spinal artery
      syndrome (ASAS) can be confirmed nowadays by MRI, whereas in the past only
      necropsy confirmation was possible. Pathophysiology and long-term prognosis may
      be better known at present and treatments more consistent. We present the
      longitudinal study and clinical features of 8 patients suffering from ASCI. All
      of them were personally studied and had MRI examinations, often with sequential
      studies. three groups must be considered: one included 4 cases of ASAS at
      cervical level, the second 2 cases of ASAS at thoracic level and the third group
      with infarction of the conus medullaris (ICM), one of them developed during
      surgical repair of an infrarenal aortic aneurysm. Motor and sensory sequelae were
      assessed in each case together with possible etiological factors. In conclusion,
      recovery after ASAS tends to be dependent on the severity of the initial deficit.
      At cervical level, clinical and morphological findings argue in favour of an
      extrinsic selective compression of the C7 right radiculo-medullary artery as
      responsible for the ASA. At thoracic level, the artery preferentially occluded
      seems to be the sulco-commisural artery as a consequence of disc compression.
      Finally, an underlying peculiarity of the pattern of arterial supply is a
      probable predisposing factor for ICM. Generally, the long-term prognosis of ASCI
      is not necessarily bad.

PMID- 7801038
TI  - [Histopathology of 110 cortical resections for drug-resistant epilepsy].
AB  - Histopathologic findings in 110 cortical resections performed for medically
      intractable epilepsy are reported. The abnormalities observed in our series fell
      into seven categories: vascular lesions, tumors, non-vascular malformative
      lesions, focal accumulation of polyglucosan bodies, non infectious inflammatory
      lesions, hippocampal sclerosis, and mild non-specific lesions. There was no
      microscopic abnormality in 14 cases. Several patients presented a double
      pathology, most often an hippocampal sclerosis as one part of the dual pathology.

PMID- 7801037
TI  - [Central serotonin receptors. Principal fundamental and functional aspects.
      Therapeutic applications].
AB  - Serotonin (5-HT) is a central neurotransmitter and a neuromodulator. This amine
      is involved in many physiological functions and pathological disorders. Most of
      its effects are mediated by specific 5-HT receptors. In the first part of this
      paper, the present knowledge of 5-HT receptors is reviewed in terms of both
      pharmacology and molecular biology. In the second part, the functional properties
      of 5-HT receptors are analyzed and their involvement in pathophysiological
      processes is discussed. Most 5-HT receptors belong to the G-protein-coupled
      receptor family (5-HT1, 5-HT2 and 5-HT4 receptors), whereas one is a member of
      the ligand-gated ion-channel receptor family (5-HT3 receptor). 5-HT1 receptors
      are characterized by their high affinity for 5-HT and comprise several
      subclasses. Most are negatively coupled to adenylate cyclase but the 5-HT1C
      subtype is linked to phospholipase C activation and resembles the 5-HT2 receptor.
      By contrast, the newly identified 5-HT4 receptor is positively coupled to
      adenylate cyclase. Most 5-HT receptors have now been cloned, but their
      physiological roles are not completely understood. Better knowledge of 5-HT
      receptors has already led to the development of new drugs, such as buspirone, a 5
      HT1A partial agonist devoid of benzodiazepine-like properties for the treatment
      of generalized anxiety. Anxiolytic properties have also been reported for 5-HT2
      and 5-HT3 receptor antagonists. A new and potent anti-migrainous drug,
      sumatriptan, has recently been selected among compounds obtained by research on
      the 5-HT1D receptor. This key receptor controls the release of monoamines, amino
      acids and peptides, and new drugs are expected in the near future. The
      therapeutic potential of 5-HT3 antagonists is impressive, as these compounds have
      potent antiemetic, promnesic and antipsychotic properties in various animal
      models. Two such drugs have already been marketed for the prevention of radiation
      induced emesis (ondansetron and granisetron) and are more potent than the
      antidopaminergic drugs. Many other data suggest that 5-HT receptors might be
      involved in other illnesses. Some drugs are in the development phase but
      identification of the relevant receptor is often difficult. Furthermore, the lak
      of specific ligands for some receptors clearly hinders functional correlations.

PMID- 7801039
TI  - [Anatomo-functional organization of the neocerebellar control pathways on the
      cerebral motor cortex].
AB  - In a first phase of this study, the topographic arrangement of the dentato
      thalamocortical projections was analyzed anatomically in albinos rats, by using
      anterograde and retrograde tracing methods. By applying intracortical
      microstimuli through the cerebral motor cortex prior to each microinjection of
      the tracer, the motor function of each injected cortical site was defined. As a
      consequence of the precise topographic arrangement of the dentato-thalamocortical
      pathways, we infer a somatotopic motor organization within the three
      cytoarchitectonic subdivisions of the cerebellar nucleus lateralis (NL), which
      corresponds to the dentate nucleus of the primate cerebellum: the hindlimb would
      be poorly represented, rostrally, whereas the head and forelimb would be more
      widely represented, within the central and caudal parts of the NL. In the second
      phase, the motor responses to direct microstimulations through the NL were
      mapped. The results confirmed the anatomofunctional arrangement deduced from the
      observations made in the first part of the study. The principles of the
      functional organization of the NL were also defined: i) the synergistic character
      of the movements induced by dentate stimulation is reflected by the activation of
      agonist as well as antagonist muscles that combine to move a particular segment
      of the body; ii) some body segments (e.g. those of the hindlimb) are represented
      within only one subdivision of the NL (single representation); others, such as
      the axio-proximal segments of the body, can be activated in a similar way from
      sites located in two or three subdivisions (multiple representation); finally,
      distal segments (digits or vibrissae) are multiply represented but activated in
      different ways by their various representation sites (specific representation):
      they can be moved independently from the parvocellular subdivision and only
      synchronously from their other representation site. The parvocellular subdivision
      of the rat NL is proposed as an equivalent to the "neodentatum" of the primate
      cerebellum.

PMID- 7801040
TI  - [Autoimmune paraneoplastic cerebellar degeneration].
AB  - Paraneoplastic cerebellar degeneration is a well-defined clinical entity
      typically associated with ovarian or breast carcinoma. Serum or CSF of these
      patients has been shown to contain autoantibodies against the cytoplasm of
      Purkinje cells. These antibodies have been referred to as anti-Yo. We report the
      case of a 67-year old woman with ovarian adenocarcinoma presenting with subacute
      cerebellar dysfunction. Her serum was found to react with the cytoplasm of
      Purkinje cells and HeLa cells. On Western blot analysis a 60 to 70 kD reaction
      was obtained. This suggests the presence of a classical anti-Yo antibody.

PMID- 7801042
TI  - [Quantitative approach of postural asynergia in cerebellar diseases].
AB  - In his original description of cerebellar asynergia, Babinski, in 1899, presented
      a patient with cerebellar dysfunction performing a backward upper trunk bending.
      When the patient tried to bend his head and trunk, his lower limbs stayed almost
      motionless, because the associated flexion of the knee and hip, usually observed
      in a normal subject, did not take place. To reassess the possibility that
      asynergia may actually be a symptom of cerebellar dysfunction, a combined
      kinematic and electromyographic (EMG) analysis of the upper-trunk bending was
      performed on 3 patients suffering from progressive cerebellar ataxia of late
      onset and showing a significant atrophy of the vermis on MRI examination.
      Compared with 3 age and sex-matched control subjects, a significant slowing down
      of the upper-trunk displacement and a marked reduction of the associated
      displacement of hip and knee was observed. EMG recordings of three pairs of
      antagonistic muscles at trunk level (rectus abdominis, erectores spinae), at
      thigh level (vastus lateralis, semi membranosus), and at leg level (tibialis
      anterior, gastrocnemius lateralis), showed that the reciprocal activation pattern
      characteristic of a normal fast movement was absent at the thigh level in the
      cerebellar patients. This lack of reciprocal activation of the thigh muscles
      during the upper-trunk bending might explain the reduction of the compensatory
      displacement of the hip and knee. It might also represent an essential feature of
      cerebellar dysfunction in provoking axial asynergia between the upper-trunk,
      which is the moving segment, and the leg, which is the supporting segment during
      equilibrium control and during whole body displacement.

PMID- 7801041
TI  - [Klippel-Trenaunay syndrome and ischemic neurologic complications].
AB  - In 1900 Klippel and Trenaunay defined a new entity characterized by cutaneous
      angioma associated with varices and hypertrophy of bone and soft tissues. The
      syndrome is present in the earliest years and becomes accentuated as the child
      grows. It typically affects one half of the body. We report two cases of Klippel
      Trenaunay syndrome. The first patient presented with flaccid paraplegia. On T1
      weighted MRI sequences a diffuse heterogeneous high-intensity signal was visible
      opposite the T8 and T9 vertebral bodies. Spinal cord angiography showed occlusion
      of the anterior spinal artery issued from Adamkiewicz's artery, suggesting
      thrombosis. Serum fibrinopeptide A level was very high and compatible with
      hypercoagulability. The second patient presented with left hemiplegia caused by a
      right superficial sylvian artery infarct, and carotid angiography showed an image
      of right internal carotid artery dissection. These two cases suggest that Klippel
      Trenaunay syndrome includes a state of hypercoagulability facilitating the
      occurrence of arterial thrombotic accidents, and an abnormality of the arterial
      wall capable of determining spontaneous dissection. A study of arterial wall
      dependent coagulation factors should establish a link between these two
      aetiological factors. All this argues in favor of a diffuse vascular pathology,
      which makes this syndrome close to phakomatoses.

PMID- 7801043
TI  - [GM2-Gangliosidosis variant B1 disclosed during adolescence by an isolated multi
      systemic involvement of the central and peripheral nervous systems].
AB  - The authors report on a Portuguese family with 3 adult brothers affected with GM2
      gangliosidosis (B1 variant) in a sibship of 4, and more specifically on one of
      these brothers with neurological onset at the age of 17. Psychosis, lower
      motoneuron involvement and dysarthria were predominant in two of the cases; the
      third had a cerebellar symptomatology. Hexosaminidase A activity, studied in
      leukocytes, was profoundly deficient when measured using the specific sulfated
      substrate, but nearly normal using a conventional assay (non-sulfated substrate).
      These results established the diagnosis of the unusual enzymological form of GM2
      gangliosidosis known as the B1 variant, which had so far not been associated with
      an adult phenotype. Molecular studies are in progress to study genotype/phenotype
      correlations in this family in comparison with known mutations in the B1 variant
      and in adult GM2-gangliosidosis. This report also emphasizes that a metabolic
      etiology, leading to genetic counselling, should be considered in some familial
      degenerative neurological disorders.

PMID- 7801044
TI  - [Bilateral infarction of the caudate nuclei].
AB  - We report the case of a 57-year-old right-handed woman, with a history of
      hypertension, who, in February 1990, suddenly developed behavioral and cognitive
      abnormalities. Prior to the onset of her illness she had been normal. On
      examination, neuropsychological testing (Wechsler Mental Test, Wechsler Adult
      Intelligence Scale Revised, Knox Cube Test) elicited attention abnormalities,
      decreased recent memory, apathy, reduced spontaneity and initiative and left
      hemiparesia. CT scan showed small low density areas in the head of both caudate
      nuclei and right internal capsule, indicating infarction. Two years later, the
      deficit had partially resolved. Apathy persisted; psychometry showed an IQ of 57.
      Bilateral damage to the head of the caudate nuclei disrupt cortical-subcortical
      connections. The caudate nucleus is an essential component of basal ganglia
      thalamo-cortical circuitry and its contribution to cognitive functions and
      behavior appears to be important.

PMID- 7801045
TI  - [Propriospinal myoclonus in a HIV seropositive patient].
AB  - We report axial myoclonic jerks causing flexion of the trunk, neck, left
      shoulder, hips and knees in a 28-years-old HIV positive patient. The clinical and
      electromyographic features of the jerks were consistent with a spinal origin and
      corresponded to the new concept of propriospinal myoclonus. No structural lesion
      was identified in this patient. Neurological examination was otherwise normal.
      HIV specific antibodies were detected in CSF, suggesting central nervous system
      infection. Spinal myoclonus should be considered an unusual and early
      manifestation of central nervous system HIV infection.

PMID- 7801046
TI  - [Type II Charcot-Marie-Tooth and dopa-sensitive Parkinson disease].
AB  - The occurrence of a dopa-sensitive parkinsonian syndrome 25 years after a
      neuropathy suggestive of Charcot-Marie-Tooth disease type II raised the
      possibility of a relationship between these two diseases. Apart from Machado
      Joseph-Azorean disease, an association of this kind seems to be exceptional and
      it can not be excluded that it was fortuitous. However, the recent description of
      7 familial and sporadic cases of a syndrome characterized by a peripheral
      neuropathy, familial in 5 of the 7 cases, followed, a few years later, by a dopa
      sensitive parkinsonian syndrome, makes it possible to consider that this
      association might have a common genetic origin.

PMID- 7801047
TI  - [Neuritis of the serratus anterior muscle associated with Borrelia burgdorferi
      infection].
AB  - A long thoracic nerve palsy developed in two patients with Borrelia burgdorferi
      infection. In both cases, pain in the shoulder preceded a scapula detachment
      suggesting first a diagnosis of neuralgic shoulder amyotrophia. In the first
      case, there was a context of typical meningoradiculitis, while the second patient
      had an isolated right shoulder amyotrophia without any other neurologic signs and
      with normal CSF analysis. A detailed anamnesis, the serology profile, and the
      good response to an adequate antibiotic treatment allowed us to attribute these
      two long thoracic nerve palsies to B. burgdorferi. This infection is important to
      consider as a possible etiology in cases of peripheral neuritis without other
      obvious causes.

PMID- 7801048
TI  - [Familial deficiency of C7 associated with adrenomyeloneuropathy].
AB  - A 24-year old man presented with recurrent meningitis resulting from familial
      deficiency of a late component of the complement system (C7). Five years later,
      he developed gait disturbance, mental impairment and loss of hearing.
      Adrenomyeloneuropathy was diagnosed by a raised plasma long chain fatty acids
      level.

PMID- 7801049
TI  - [Myasthenic syndrome disclosing Hodgkin disease].
AB  - A case of myasthenia associated with Hodgkin's disease with probable invasion of
      the thymus is reported. Five cases of association between lymphomatous thymoma
      and myasthenia (2 Hodgkin's thymomas and 3 non-Hodgkin's lymphomatous thymomas)
      have previously been reported. Myasthenia healed after the lymphoma was treated.
      This association raises pathogenic problems in the 3 cases of non-Hodgkin's
      thymoma where invasion of the thymus erased all its normal structure.

PMID- 7801050
TI  - [Unconjugated pteridines and neuromeningeal infections].

PMID- 7801051
TI  - Kashin-Beck disease. An analysis of research and public health activities based
      on a bibliography 1849-1992.
AB  - The main feature of Kashin-Beck disease (KBD) is short stature caused by multiple
      focal necroses in the growth plate of the tubular bones. This leads to a
      secondary, sometimes severe osteoarthrosis. The disease was first described in
      Russia from the Bajkal area by Kashin 1848 and later, 1906, by Eugene Beck.
      Modern literature is mainly from China. The main theory originally proposed by
      Russian investigators was that KBD was caused by a toxic effect of mycotoxin. The
      focus on the disease gradually shifted to China where the causal theory has been
      based on the effects of selenium deficiency and its interaction with mycotoxins.
      These main hypotheses may be unified in one theory. KBD is appreciated as a
      public health problem estimated to affect some 1-3 million people across China.
      National and provincial registers on KBD exist for selected affected areas.
      Current incidence is probably declining. Preventive efforts have been undertaken
      but are usually not controlled for effectiveness nor by putative causal
      mechanisms. More research into the causal mechanisms is required. A combination
      of difficulties to obtain literature, including primary material together, and
      cultural and language barriers have been a main obstacle to more active
      participation by the international research community. This bibliography is an
      attempt to help improve this situation. The bibliography covers the period 1849
      1992. The analysis of this bibliography shows a broad and intensive, though
      sometimes insufficiently coordinated research. Many authorities and research
      bodies are involved. The possibility to develop coordinated projects within a
      common framework, and thus to use research results to prevent KBD, has been a
      major source of inspiration in making this review. The review covers 499
      publications directly related to KBD and 1415 references to these publications.
      KBD publications have been retrieved from conventional international journals,
      usually in English, publications in Russian, as well as unpublished reports in
      Chinese provided at site visits. The papers are classified by key words. The
      references in these publications have also been similarly classified and are in
      part analysed. Based on publications identified from several sources, direction
      of research and public health efforts from 1848 to 1992 are described. Finally,
      mainly based on questions raised by and recommendations from a WHO workgroup
      meeting in 1992, some major components of research activities and public health
      program are proposed.

PMID- 7801052
TI  - Methotrexate treatment in the management of giant cell arteritis.
AB  - Eleven newly-diagnosed GCA patients were included in a prospective open study and
      treated with high initial prednisone doses, a quick-tapering CS schedule and
      weekly oral MTX for two years. It took a mean of 14 weeks to reach a 10 mg/day
      dose of prednisone and 29.8 weeks until steroid withdrawal. The mean cumulative
      dose of prednisone was 3.4 g. Two patients relapsed and five developed CS side
      effects. No serious MTX side effects were observed. Our results suggest that MTX
      is safe and could be useful in the therapy of GCA.

PMID- 7801053
TI  - Learned helplessness and its correlation to impairment, pain, anxiety and
      depression in rheumatoid arthritis.
AB  - A Swedish version of the self-report instrument Arthritis Helplessness Index
      (AHI) is presented. Validity and reliability of the translation has been
      analyzed. 100 consecutive patients with rheumatoid arthritis (RA) were studied,
      78 of which completed 2 self-administered questionnaires with AHI, impairment,
      pain, anxiety and depression. Furthermore 20 of the patients were interviewed
      with regard to AHI. Forty-two other patients with RA were analyzed for
      correlation between AHI and biochemical activity and Signals of Functional
      Impairment (SOFI). We conclude that the Swedish version of AHI has satisfactory
      validity and reliability. It correlates with age, physical impairment, pain,
      anxiety and depression but not with sex or disease activity. Five of the original
      15 items could for various reasons be omitted, leaving a 10 statement instrument.
      AHI is promising as a variable in future outcome studies of RA.

PMID- 7801054
TI  - Occupation, occupational exposure to chemicals and rheumatological disease. A
      register based cohort study.
AB  - The cumulative incidence of rheumatoid arthritis (RA) was compared between
      different occupations, and between different exposure groups based on a job
      exposure matrix (JEM). The study population comprised those subjects who in 1980
      lived in one of 13 Swedish counties, were born between 1905 and 1945, and who had
      stated the same occupation in the censuses of 1960 and 1970, a total of 375,035
      men and 140,139 women. The study population was followed concerning hospital care
      for rheumatoid arthritis in 1981-1983 by lineage to the Swedish Hospital
      Discharge Register. In general there were rather small differences in the
      relative risk of RA in different exposure groups and different occupations. Most
      of the occupations associated with an increased risk of RA were occupations in
      which it was possible to work when the disease was present, i.e. cost
      accountants, estimating clerks and working proprietors in the retail trade.
      However, an increased relative risk of RA was also observed in some occupations
      where selection of RA patients out of heavy work should have biased genuinely
      increased relative risks towards unity. Such occupations were farmers,
      upholsterers, lacquerers, concrete workers, and hair-dressers. Substantial
      handling of organic solvents, according to the JEM, was associated with an
      increased relative risk.

PMID- 7801055
TI  - Abnormal colonic microbial function in patients with rheumatoid arthritis.
AB  - The aim of this study was to examine the microflora-associated characteristics
      (MACs) of faecal samples of patients with rheumatoid arthritis (RA) and to
      evaluate the actions of sulphasalazine (SASP) on these MACs. The conversion of
      cholesterol to coprostanol, the production of urobilinogen, the degradation of
      faecal tryptic activity (FTA) and of beta-aspartylglycine were measured in faecal
      samples from 19 patients treated with SASP and 21 patients not treated with this
      medication. A control group of 21 healthy subjects was sex- and age-matched with
      the untreated patients. The conversion of cholesterol to coprostanol showed a
      bimodal distribution. The frequency of high converters in patients without SASP
      treatment was higher than in healthy subjects (p < 0.05). Treatment with SASP
      markedly increased the FTA and reduced the urobilinogen values, as compared to
      the untreated patients (p < 0.05). Beta-aspartylglycine was not found in any
      faecal samples. The results indicate that patients with RA have an abnormal
      formation of coprostanol, which is ascribed to alterations in the function of the
      Eubacteria species. In patients with RA, SASP treatment induces disturbances in
      the metabolism of the microflora.

PMID- 7801056
TI  - Plasma endothelin-1 concentrations in patients with Behcet's disease.
AB  - Plasma Endothelin-1 (ET-1) concentrations were determined by radio immunoassay in
      30 patients with Behcet's disease at various stages and 20 healthy subjects. Mean
      ET-1 plasma concentrations were significantly (p < 0.001) increased in patients
      with active Behcet's disease (35.99 +/- 5.06 fmol/ml, mean +/- standard error)
      compared to concentrations found in healthy volunteers (10.98 +/- 0.84 fmol/ml).
      No difference in plasma ET-1 level was observed between patients with inactive
      Behcet's disease (12.98 +/- 1.14 fmol/ml) and volunteers. Increased plasma levels
      of ET-1 in patients with Behcet's disease may be attributable to increased
      secretion or leakage of this mitogen from injured vascular endothelial cells.
      These results indicate that ET-1 may play an important pathogenetic role in the
      development or progression of vasculitis common to Behcet's disease. Plasma
      concentrations of ET-1 correlates with the activity of illness.

PMID- 7801057
TI  - Salivary gland scintigraphy in subjects with and without symptoms of dry mouth
      and/or eyes, and in patients with primary Sjogren's syndrome.
AB  - The major salivary glands were examined with 99m-Tc-pertechnetate scintigraphy in
      randomly selected subjects with (n = 30) and without (n = 12) symptoms of dry
      mouth and/or eyes, and in patients with primary Sjogren's syndrome (1 degree SS,
      n = 17). The scans were quantitatively evaluated and compared to other objective
      tests used to diagnose 1 degree SS. As compared with those for asymptomatic
      subjects, most values for the scintigraphic variables were non-significantly
      lower for symptomatic subjects and the time-activity curves were slightly flatter
      for all major salivary glands. In patients with 1 degree SS most values for the
      scintigraphic variables were significantly lowered and the submandibular glands
      were the glands most affected, as reflected in a flat time-activity curve, while
      the parotid glands were mainly affected during stimulated secretion. The
      scintigraphic variables correlated with the self-rated dryness of mouth in
      symptomatic subjects and with the abnormality of sialometry results in patients
      with 1 degree SS. We conclude that salivary gland scintigraphy is a sensitive and
      valid method to measure salivary gland function and abnormalities.

PMID- 7801058
TI  - Quantitative assessment of joint pain following treatment of rheumatoid arthritis
      with ibuprofen cream.
AB  - The antiinflammatory effect of percutaneous application of NSAID (DOLGIT cream)
      was evaluated quantitatively on 11 patients with symmetric rheumatoid arthritis
      of the metacarpophalangeal and/or proximal interphalangeal joints. The pressure
      pain detection threshold (PDT) and pressure pain tolerance threshold (PTT) on the
      test joints were measured before and on days 3 and 7 after double-blind placebo
      controlled application of NSAID cream. The clinical pain was assessed by a visual
      analog scale (VAS) following controlled finger movements. The relative median PDT
      differences between NSAID and placebo treatment median were 10 kPa (N.S.) on day
      3 and 17 kPa (N.S.) on day 7. The corresponding median differences in PTT were -5
      kPa (N.S.) and 23 kPa (P < 0.05), respectively. The corresponding median
      decreases in VAS score were 4.2 mm (N.S.) and 15.5 mm (N.S.), respectively. The
      experimental joint pressure techniques can assess selectively pain from small
      joints and is a new useful tool to evaluate antinociceptive and/or
      antiinflammatory effects.

PMID- 7801059
TI  - Side effects of sulphasalazine in patients with rheumatic diseases or
      inflammatory bowel disease.
AB  - We compared sulphasalazine (SSZ) toxicity in 140 patients (196 treatment periods)
      of two patient groups, those with rheumatoid disease (RD) (rheumatoid arthritis,
      RA, ankylosing spondylitis, AS), and those with inflammatory bowel disease (IBD).
      Adverse events occurred in 64% of all patients (highest 85% in AS and lowest 50%
      in ulcerative colitis, CU). There were more recorded adverse events in patients
      with RD than in patients with IBD. Hepatic side effects were more frequent in
      patients with IBD than in patients with RD. Adverse events were the most common
      reason for discontinuing the treatment (in 34.8% of AS patients, in 46.2% of RA
      patients, in 21.7% of the Crohn's disease patients and in 32.6% of CU patients).
      There were no lethal or permanent adverse events. Age, sex, rheumatoid factor and
      HLA-B27 antigen positivity did not influence on the appearance of adverse events.

PMID- 7801060
TI  - Interrater reliability of the 7-level functional independence measure (FIM)
AB  - The Functional Independence Measure (FIM) is an 18-item, 7-level scale developed
      to uniformly assess severity of patient disability and medical rehabilitation
      functional outcome. FIM interrater reliability in the clinical setting is
      reported here. Clinicians from 89 US inpatient comprehensive medical
      rehabilitation facilities newly subscribing to the uniform Data System for
      Medical Rehabilitation from January 1988-June 1990 evaluated 1018 patients with
      the FIM. FIM total, domain and subscale score intraclass correlation coefficients
      (ICC) were calculated using ANOVA; FIM item score agreement was assessed with
      unweighted Kappa coefficient. Total FIM ICC was 0.96; motor domain 0.96 and
      cognitive domain 0.91; subscale score range: 0.89 (social cognition) to 0.94
      (self-care). FIM item Kappa range: 0.53 (memory) to 0.66 (stair climbing). A
      subset of 24 facilities meeting UDSMR data aggregation reliability criteria had
      Intraclass and Kappa coefficients exceeding those for all facilities. It is
      concluded that the 7-level FIM is reliable when used by trained/tested inpatient
      medical rehabilitation clinicians.

PMID- 7801061
TI  - Changes in muscle morphology, strength and enzymes in a 4-5-year follow-up of
      subjects with poliomyelitis sequelae.
AB  - Twenty subjects with polio sequelae were studied on two occasions 4-5 years apart
      by means of dynamometer measurements of knee-extension and flexion strength and
      muscle biopsy for histochemical and enzymatic analyses. The subjects were divided
      into those who reported (unstable, n = 12) and did not report (stable, n = 8) new
      or increased muscle weakness in the tested leg between the two examinations.
      Muscle strength decreased significantly in the unstable subjects, but only for
      knee-flexion in the stable subjects. However, the endurance test comprising 50
      consecutive knee-extensions at 180 degrees/sec showed increased fatigability at
      the second examination only in the stable subjects. Most subjects had markedly
      increased muscle fiber areas, which in some subjects increased further, but in
      those already with very extreme hypertrophy the fiber size decreased.
      Capillarization and activity of citrate-synthase were decreased at the initial
      examination, but no significant further reduction was observed at the second
      examination. The results demonstrate individual patterns in the compensatory
      process for the presumed loss of motor units.

PMID- 7801062
TI  - Risk indicators in the psychosocial and physical work environment for work
      related neck, shoulder and low back symptoms: a study among blue- and white
      collar workers in eight companies.
AB  - The study was based on a questionnaire and included 209 white-collar workers and
      241 blue-collar workers in eight companies. The questionnaire deals with
      musculoskeletal symptoms, psychosocial and physical load factors. The
      relationship between job factors and neck, shoulder and low-back symptoms was
      analysed. The Nordic Musculoskeletal Questionnaire (NMQ) was supplemented with an
      additional question regarding whether or not the symptoms were believed to be
      related to work. The associations between the psychosocial factors and
      musculoskeletal symptoms were substantially higher when solely work-related
      symptoms were included in the analyses; these associations were of the same
      magnitude as that between several physical work load factors and work-related
      musculoskeletal symptoms. This study suggests that calculations of associations
      based solely on the NMQ, without the inclusion of questions to elicit reports of
      symptoms that are believed to be work-related, could have a powerful effect
      masking consequence.

PMID- 7801063
TI  - Back pain in school children. A study among 1178 pupils.
AB  - The purpose of this study was to determine the prevalence of back pain in school
      children and the role of several contributing factors; 1178 school children of
      both sexes answered a previously validated questionnaire. The cumulative
      prevalence of back pain was 51.2%. Lumbar and leg pain, and thoracic pain were
      more common. After multivariate analysis, five qualitative variables were
      correlated with back pain with a statistical, significant positive correlation
      with age, previous back injury, volley-ball, female sex and time spent watching
      television.

PMID- 7801064
TI  - Flexibility of the spine: normative values of goniometric and tape measurements.
AB  - A sample of 508 male and female white-collar and blue-collar employees aged 35 to
      54 years were examined clinically to determine the reliability of spinal
      flexibility measurements using inclinometers and a tape measure, and to determine
      the normal values of cervical sagittal movements, lateral flexion, lumbar flexion
      and extension, trunk rotation and sidebending. Spinal flexibility decreased with
      advancing age, particularly among the blue-collar workers. Male predominance was
      observed in lumbar flexion and rotation and female predominance in cervical
      flexion-extension-movement. Spinal flexibility was negatively related to the
      experience of disabling pain. The strongest connections were between cervical
      flexion-extension-movement and neck pain, and between trunk sidebending and low
      back pain during the preceding year. The interobserver reliabilities were found
      to be generally good for all these measurements, and trunk sidebending showed the
      highest reliability coefficients. The intraobserver reproducibility (checked at a
      one-year interval) was acceptable only for cervical flexion-extension movement,
      cervical sidebending and trunk sidebending.

PMID- 7801065
TI  - Low power Ga-Al-As laser treatment of painful osteoarthritis of the knee. A
      double-blind placebo-controlled study.
AB  - The aim of this double-blind study was to evaluate the effect of low power Ga-Al
      As laser treatment on chronic pain related to osteoarthritis of the knee with
      periarticular tender points. Twenty-nine out-patients with uni- or bilateral
      osteoarthritis of the knee were included and randomly assigned to treatment with
      either laser or placebo laser. Fourteen patients received active laser treatment
      and all patients included completed the study. The effect variables were daily
      levels of pain, analgesic requirements, palpation tenderness and isokinetic
      quadriceps strength. Each patient participated in the study for 9 weeks and
      registered daily level of pain and consumption of analgesics. In weeks 4, 5 and 6
      the patients received a total of nine treatments, each of 15 min and administered
      to periarticular tender points. The dose per treatment was 22.5 joule. No
      significant differences in any of the effect variables were found between the two
      groups before, during or after treatment. With regard to the patients' overall
      assessment there was a clearly demonstrable positive effect of treatment in both
      groups. This is likely to be due to a placebo effect.

PMID- 7801066
TI  - Quantitative analysis of rising from a chair in healthy and hemiparetic subjects.
AB  - In 15 healthy and 20 hemiparetic persons we studied standing-up by two force
      plates. Phases before and after the seat-off, force distribution and centre of
      gravity displacement were assessed. The patients rose significantly slower. The
      force ratios after seat-off differed significantly between the groups (0.88 vs
      0.68). Left/right hemiparetic patients put more weight on the affected limb in
      18%/11% of the trials before seat-off, with its insufficient use after it mainly
      in the left patients. At seat-off, projection of the centre of gravity fell
      within the support area in hemiparetic patients, and 3 cm behind it in healthy
      subjects. With larger lateral displacement of the centre of gravity in the
      hemiparetic group, left hemiparetic patients mostly shifted their weight to the
      non-affected side and right hemiparetic patients to both sides. Weight
      distribution and mediolateral displacement of the centre of gravity in the left
      and right hemiparetic patients were considered.

PMID- 7801067
TI  - Outcomes of geriatric discharge planning. A quality assurance study from a
      geriatric rehabilitation ward.
AB  - The outcome of a discharge planning procedure at a geriatric rehabilitation ward
      was studied with an interdisciplinary and multidimensional approach, where
      medical, nursing, functional and psychosocial factors were included. The
      patient's own expectations and attitude to functional performance and outcome
      were explored in an interview at the day of discharge and one month later in a
      follow-up telephone interview. Data were also collected from registers and
      medical and professional records. All the 36 patients discharged to their own
      homes, mostly after home assessment, or to old people's homes were followed up.
      The median rehabilitation stay was 30 days. Their medical status was stable over
      time and nursing interventions remained frequent. The functional level was
      unchanged for 18, and further enhanced for 10 patients. Most patients felt secure
      at home and received the home help they anticipated. Worries were expressed by
      one-third on realistic grounds, mainly medical or ideas on the accommodation.
      Some interventions were required and carried out by the team. Home living was as
      expected or better for two-thirds of the patients. The timing and the patient's
      situation at discharge seemed to have been well assessed, with an overall
      positive outcome after a month at home. Further development of practical
      multidimensional evaluations adapted to elderly patients is necessary in a
      quality assurance perspective.

PMID- 7801068
TI  - Mechanisms of the combined effect of asbestos and smoking in the etiology of lung
      cancer.
AB  - The joint effects of exposure to two known lung carcinogens, tobacco smoking and
      asbestos, are reviewed. The variable pattern of interaction--ranging from
      supramultiplicative to less than additive--may reflect the fact that both
      asbestos and smoking are complex carcinogens which can affect more than one stage
      of lung carcinogenesis. The joint effect of two such agents will depend on the
      relative magnitude of the effects at each stage. The epidemiologic evidence from
      studies of insulation workers with high exposures suggests an interaction that
      approximates the multiplicative model, indicating that each of the two factors
      has an independent action on the multistage process of carcinogenesis. Very
      limited information is available on the interaction between these two agents in
      causing specific histological types of lung cancer. Both tobacco smoke and
      asbestos fibers can be genotoxic and cytotoxic and cause proliferative lesions in
      the lungs. Tobacco smoke is known to contain carcinogens that bind to critical
      genes in DNA (deoxyribonucleic acid) and cause mutations. Asbestos fibers may
      cause chronic inflammation of the lungs, which releases various cytokines and
      growth factors, and therefore may provide a possible selective growth advantage
      for mutated cells.

PMID- 7801069
TI  - Asbestos exposure and the risk of lung cancer in a general urban population.
AB  - OBJECTIVES: The aim of the study was to investigate the asbestos-associated risk
      of lung cancer according to histological type of cancer, lobe of origin,
      pulmonary concentration, and type of amphibole fibers and also to estimate the
      etiologic fraction of asbestos for lung cancer. METHODS: The pulmonary
      concentration of asbestos fibers in 113 surgically treated male lung cancer
      patients and 297 autopsy cases among men serving as referents was determined by
      scanning electron microscopy. The age- and smoking-adjusted odds ratios of lung
      cancer were calculated according to pulmonary fiber concentration for all lung
      cancer types, squamous-cell carcinoma, and adenocarcinoma and for the lower-lobe
      and the upper- and middle-lobe cancers. RESULTS: The risk of lung cancer was
      increased according to the pulmonary concentration of asbestos fibers (f) of 1.0
      to 4.99 x 10(6) f.g-1 [odds ratio (OR) 1.7] and > or = 5.0 x 10(6) f.g-1 (OR
      5.3). The odds ratios associated with fiber concentrations of > or = 1.0 x 10(6)
      f.g-1 were higher for adenocarcinoma (OR 4.0) than for squamous-cell carcinoma
      (OR 1.6). The asbestos-associated risk was higher for lower lobe tumors than for
      upper lobe tumors. The risk estimates for anthophyllite and crocidolite-amosite
      fibers were similar, except for the risk of squamous-cell carcinoma. An etiologic
      fraction of 19% was calculated for asbestos among male surgical lung cancer
      patients in the greater Helsinki area. CONCLUSIONS: Past exposure to asbestos is
      a significant factor in the etiology of lung cancer in southern Finland. The
      asbestos-associated risk seems to be higher for pulmonary adenocarcinoma and
      lower-lobe tumors than for squamous-cell carcinoma and upper-lobe tumors.

PMID- 7801070
TI  - Cancer mortality in a historical cohort study of workers exposed to styrene.
AB  - OBJECTIVES: The goal of this study was to determine whether exposure to styrene
      is associated with an increased risk for neoplasms of the lymphatic and
      hematopoietic tissues. METHODS: A historical cohort study was conducted in
      Denmark, Finland, Italy, Norway, Sweden, and the United Kingdom. It involved
      40,688 workers ever employed in the reinforced plastics industry, where high
      exposure to styrene occurs. Exposure to styrene was reconstructed through job
      histories and environmental and biological monitoring data. Cause-specific
      national death rates were used as the reference. Poisson regression was applied
      for internal comparisons. RESULTS: Among the exposed workers, no excess was
      observed for mortality from all neoplasms. Mortality from neoplasms of the
      lymphatic and hematopoietic tissues increased with time since first exposure and
      average level of exposure to styrene, but was not consistently associated with
      duration of exposure or with cumulative exposure. CONCLUSIONS: These findings
      leave open the possibility of an excess risk of neoplasms of the lymphatic and
      hematopoietic tissues among workers exposed to styrene.

PMID- 7801071
TI  - Retrospective assessment of exposure through modeling in a study on cancer risks
      among workers exposed to phenoxy herbicides, chlorophenols and dioxins.
AB  - OBJECTIVES: The study aimed at developing a model for the retrospective
      assessment of exposures in epidemiologic studies when little or no data on past
      exposures are available. METHODS: A deterministic model was developed for the
      level of exposure by industrial hygienists involved in an international study on
      cancer risks among phenoxy herbicide or chlorophenol manufacturing workers and
      pesticide sprayers. The general source-receptor model was used as the conceptual
      framework for the model. RESULTS: The model included variables related to job,
      the emission of chemicals, contact with chemicals, personal protection, and other
      relevant determinants of exposure. Cumulative dose indices were calculated from
      the duration of exposure (from the work histories) and the level of exposure
      (from the model). CONCLUSIONS: Deterministic modeling in complex exposure
      situations may provide more valid and reliable results than its conventional
      alternative, subjective assessment by an expert.

PMID- 7801072
TI  - Incidence of lymphohematopoietic malignancies among styrene-exposed workers of
      the reinforced plastics industry.
AB  - OBJECTIVES: The goal of this study was to determine the risk of
      lymphohematopoietic malignancies for workers exposed to styrene. METHODS: This
      was a historical cohort study. The observed numbers of newly diagnosed cases of
      lymphohematopoietic malignancies in the study population were compared with
      expected numbers based on the national rates. The study took place in the Danish
      reinforced plastic industry, in which high exposure levels of styrene occur
      frequently in an environment free of most other suspected carcinogens. Altogether
      36,525 male employees of 386 companies producing reinforced plastics and 14,254
      nonstyrene exposed employees of similar industries were studied. RESULTS: An
      insignificantly increased standardized incidence ratio (SIR) of 1.22 [95%
      confidence interval (95% CI) 0.88-1.65] was found for leukemia among all
      employees of the reinforced plastics industry. Workers employed in the 1960s (the
      period with the highest recorded styrene levels) or in companies with the highest
      exposure probability showed increased SIR values of 1.54 (95% CI 1.04-2.19) and
      1.38 (95% CI 0.75-2.32), respectively. Both estimates increased when a 10-year
      latency period was considered. CONCLUSIONS: An increased risk of leukemia was
      shown for workers in the early phase of the reinforced plastics industry in
      Denmark. If this association is not due to chance or confounding, the most likely
      cause is styrene exposure.

PMID- 7801073
TI  - Internal load of aluminum and the central nervous system function of aluminum
      welders.
AB  - OBJECTIVES: Because the brain is the recognized target organ for aluminum
      toxicity, internal aluminum load and central nervous system functions were
      investigated among aluminum welders in a shipyard. METHODS: Seventeen male
      welders with a mean age of 37 (range 24-48) years and a history of about four
      years of metal inert-gas welding on aluminum were the subjects. Aluminum in serum
      (S-Al) and urine (U-Al) was analyzed with graphite-furnace atomic absorption
      spectrophotometry. Central nervous system functions were examined with
      neuropsychological tests, symptom and mood questionnaires, quantitative
      electroencephalography (QEEG), and P300 evoked responses. RESULTS: The mean S-Al
      concentration was 0.21 (range 0.03-0.64) mumol.l-1 and the mean U-Al was 2.8
      (range 0.9-6.1) mumol.l-1. Although the welders performed normally on the
      neuropsychological tests, there was a negative association between all four
      memory tests and U-Al and a positive association between the variability of
      visual reaction times and S-Al. In the QEEG, the amount of delta and theta
      activity in the frontal region correlated positively and the amount of alpha
      activity in the frontal region correlated negatively with S-Al. CONCLUSIONS: The
      S-Al and U-Al measurements indicated increased internal loads of aluminum in most
      of the welders. This finding is compatible with slowly eliminated aluminum from
      tissues. The neuropsychological assessment suggested disturbing effects of
      aluminum on short-term memory, learning, and attention. In the QEEG, a
      corresponding exposure-effect relationship was found for activity in the frontal
      region. Further studies are needed on the possibility that exposure to aluminum
      welding fumes causes harm to human health.

PMID- 7801074
TI  - Cardiovascular diseases among foundry workers exposed to carbon monoxide.
AB  - OBJECTIVES: The study investigated long-term effects of carbon monoxide (CO)
      exposure on foundry workers' morbidity and mortality from cardiovascular
      diseases. METHODS: The study population comprised a cohort of 2857 men hired in
      1950--1972 by 20 Finnish foundries and also 931 men who were still active in
      1972, exposed for at least 4.2 years, took part in a health examination in 1973;
      653 of the 931 had also been members of the cohort. These groups were followed to
      the end of 1987. RESULTS: The age-standardized incidence density rate (ID/1000
      person-years) for compensated medication for hypertension was 4.7 for the
      unexposed workers and 9.4 for those exposed [rate ratio (RR) 2.0, 95% confidence
      interval (95% CI) 1.28--2.92]; for the iron foundry workers the rates were 4.7
      and 9.9 (RR 2.1, 95% CI 1.24--3.38), respectively. During 1950--1987, 255
      cardiovascular deaths were observed (284 expected according to national rates).
      The observed number of deaths due to ischemic heart disease was 183 (203
      expected). The iron foundry workers' mortality rate for cardiovascular deaths was
      99% of the national expected value. No remarkable differences were found between
      the CO-exposure categories. For the health-examination group, the age
      standardized incidence rate for compensated medication for hypertension was 9.1
      for the unexposed nonsmokers and 21.4 for the exposed smokers (RR 2.3, 95% CI
      0.97-6.35); the difference originated among the iron foundry workers, for whom
      the rates were 8.1 and 24.0 (RR 3.0, 95% CI 0.96--9.78), respectively. The age
      standardized mortality rate (ID/1000 person-years) was 2.7 for nonsmokers with no
      or slight CO exposure and 9.2 for exposed smokers (95% CI 1.13--12.11). This
      difference was mainly caused by ischemic heart disease. CONCLUSIONS: The results
      indicate that CO exposure increases the risk of cardiovascular morbidity and
      mortality.

PMID- 7801075
TI  - Noise exposure, noise annoyance, use of hearing protection devices and distress
      among blue-collar workers.
AB  - OBJECTIVES: This study tested the hypotheses that, in high noise levels [> or =
      85 dB(A)], hearing protection devices are used largely by workers sensitive to
      noise, as reflected by reports of noise annoyance, and that the usage would
      reduce distress symptoms. METHODS: Data collected from 1587 healthy male blue
      collar workers included noise exposure level, noise annoyance, use of hearing
      protection devices, distress symptoms (somatic complaints and poststress
      irritability), and possible confounding by age, education and ethnic origin.
      RESULTS: Multiple logistic regression results indicated that the use of hearing
      protection devices was related to noise exposure level [odds ratio (OR) 2.94, 95%
      confidence interval (95% CI) 2.58--3.30], but more so to high noise annoyance (OR
      3.03, 95% CI 2.77--3.29), even after control for age, education, and ethnic
      origin. No interaction was found between noise level and noise annoyance. These
      findings highlight the contribution of noise annoyance to the use of hearing
      protection devices. Of the 42.6% of workers using hearing protection devices in
      the presence of high ambient noise, 60% were highly annoyed. Noise-annoyed
      workers also tended to wear hearing protection devices even in low noise levels.
      The use of hearing protection devices was associated with lower distress symptoms
      among the low and moderately annoyed workers, but among the highly annoyed
      workers the reverse was true. CONCLUSIONS: Thus, for the highly annoyed workers,
      the use of hearing protection devices was perhaps an additional source of stress.
      One immediate implication of this study is that future intervention procedures
      should focus on unannoyed workers who tend to use hearing protection devices
      less.

PMID- 7801076
TI  - Parkinsonism after chronic exposure to the fungicide maneb (manganese ethylene
      bis-dithiocarbamate).
AB  - Permanent parkinsonism was observed in a man with chronic exposure to the
      fungicide maneb (manganese ethylene-bis-dithiocarbamate). Symptoms developed at
      37 years of age, two years after exposure had ceased. To our knowledge, this is
      the second report on parkinsonism associated with exposure to maneb. Manganese is
      a well-known parkinsonigen toxin in humans. More recently, it has been shown that
      dithiocarbamates can also induce extrapyramidal syndromes. The biochemical
      effects of manganese and dithiocarbamates are reviewed and their possible
      neurotoxic mechanisms are discussed. Both of these components may have played a
      role in this case.

PMID- 7801077
TI  - Erythropoietin-independent colonies of red blood cells and leukocytosis in a
      worker exposed to low levels of benzene.
AB  - BACKGROUND: Exposure to high levels of benzene commonly results in the
      suppression of hemopoiesis, although cases of leukocytosis and leukocytosis with
      thrombocytosis have been reported. No hematologic abnormalities have generally
      been found with exposure to low levels of benzene. METHODS: A pipe fitter exposed
      to low levels of benzene (time-weighted average 0.9 ppm) developed leukocytosis.
      His blood counts and growth of erythroid burst forming units (BFU-E) was followed
      with and without the addition of erythropoietin. RESULTS: Erythropoietin
      independent BFU-E colonies were increased to 40 per 4 x 10(4) cells (normal < 3
      per 4 x 10(4) cells). Both the leukocyte count and the number of erythropoietin
      independent BFU-E colonies decreased when exposure to benzene was terminated. On
      reexposure the white blood count again increased. After the work was terminated,
      the white blood count returned to normal, as did the number of erythropoietin
      independent BFU-E colonies, over a period of 12 months. CONCLUSIONS: Our findings
      suggest that even low levels of benzene can result in perturbations of the
      hemopoietic system. Further studies are warranted to determine whether these
      findings are idiosyncratic, coincidental, or a more general phenomenon.

PMID- 7801078
TI  - New epidemics in occupational health.

PMID- 7801079
TI  - [Cognitive and psychological effects on the population of a cardiac emergency
      campaign].
AB  - The major part of the delay from onset of symptoms of acute myocardial infarction
      to arrival in hospital is caused by patients' delayed reporting. Therefore, a
      media campaign was initiated by the Swiss Heart Foundation with the goal of
      informing people about the seriousness of chest pain and about the importance of
      proper action in these situations. An initial 2 months' national campaign was
      followed by a 3 weeks' intensive local campaign in a mixed urban/suburban area in
      central Switzerland. The aim of the study was to evaluate the effects of this
      media campaign on patients information and reaction in case of cardiac emergency,
      and to study the possible impact of this campaign on anxiety levels and other
      emotions. Telephone interviews were performed before and after both the national
      and the local campaign using a cohort of 500 persons in a longitudinal and 4 x
      500 persons in a cross-sectional study. The information had reached about 50% of
      the population by the end of the local campaign. The percentage of persons who
      would call the emergency medical services immediately in case of chest pain
      increased from 40% to 57% in the cross-sectional and from 48% to 65% in the
      longitudinal study (p < 0.001), and the percentage of persons who would call the
      ambulance team immediately on witnessing a person with a heart attack increased
      from 25 to 92% in the cross-sectional and to 96% in the longitudinal study (p <
      0.001). Anxiety levels and other negative emotions decreased slightly during the
      campaign (p < 0.05), whereas feelings of personal safety revealed a slight
      increase (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7801080
TI  - [Voluntary poisoning with dexfenfluramine (Isomeride)].
AB  - Dexfenfluramine is one of the most widely prescribed appetite suppressant drugs
      in Switzerland because of its enhancing effect on certain weight-reducing diets.
      Nevertheless, the effects of acute intoxication are not well documented. We
      recently observed a young adolescent girl who ingested large quantities of the
      drug to achieve a rapid weight loss. She presented with tachycardia, high blood
      pressure, mydriasis, fever and behavioral disorders. All signs and symptoms
      cleared after 48 hours. The clinical picture is akin to amphetamine intoxication,
      in view of the similarity of the two drugs' metabolites.

PMID- 7801081
TI  - [Ethics of antibiotherapy in geriatric medicine].
AB  - The high frequency of infections in the elderly, at home as well as in
      institutions, raises the question of the place antibiotic therapy should occupy.
      Too often, unfortunately, antibiotic therapy is prescribed indiscriminately in
      cases of infection. Between therapeutic abstention and overtreatment there is
      room for a more rational and adapted medical decision which is the outcome of a
      clinical process integrating a rigorous biomedical approach, taking due account
      of the environment, the functionality and the quality of life of the elderly
      patient. The importance of human, ecological, pharmacological and economic
      constraints should lead to deeper consideration of the appropriateness of
      antibiotic therapy in geriatric practice.

PMID- 7801082
TI  - [Infectious risk factors with special attention to elderly patients].
AB  - This short review focuses on non-specific defences against infectious agents and
      the immune response in the elderly patient. The problem of hypogammaglobulinemia
      in patients with myeloma or leukemia, and its treatment with intravenous
      immunoglobulins, is also discussed.

PMID- 7801083
TI  - [Proposal for a shortened i.v. antibiotic treatment as cost-saving measure in the
      treatment of uncomplicated infections].
AB  - New oral antibiotics with high rates of absorption and good bioavailability make
      it possible to reduce costs by shortening the i.v. treatment period. During two 2
      month periods we analyzed every patient of the Medical Department who received
      i.v. treatment. We tried to reduce i.v. treatment duration simply by discussion
      with the responsible physician, guided essentially by the clinical course. The
      number of patients with reduced i.v. treatment were compared with a control
      period. We found that by this means, an i.v. treatment period of 4-7 days could
      often be reduced to 1-3 days. The main target pathologies with corresponding cost
      savings appeared to be infections of the lower respiratory tract, with a cost
      saving potential of 1.4 days (p < 0.0001) and urinary tract infections with a
      cost-saving potential of SFr. 179.-(US$ 138.-) per case.

PMID- 7801084
TI  - [Radiotherapy in small animal medicine: fundamentals, indications and
      significance].
AB  - This article describes the general principles of radiation therapy, reviews the
      indications for this treatment modality and discusses the response of tumors and
      normal tissue to radiation. Radiation modalities and treatment protocols
      currently available in Switzerland are presented. Treatments of spontaneous
      tumors in animals contribute to the development of radiation therapy in human
      medicine at the same time.

PMID- 7801085
TI  - [Pharmacokinetics of baytril (enrofloxacin) in dogs].
AB  - Baytril with the active ingredient enrofloxacin was given to four dogs in a
      single intravenous and oral dose of 5 mg/kg body weight. Measured plasma
      concentrations were different depending on the method of analysis used. Using
      high performance liquid chromatography quantitative determination of both
      enrofloxacin and its main metabolite ciprofloxacin is possible whereas
      antimicrobially active substance is measured by bioassay. Ciprofloxacin occurred
      early in the concentration-time curves after intravenous and oral administration
      of the parent drug enrofloxacin with cmax 0.2 and 0.3 microgram/ml, respectively,
      at tmax 2 and 4 h, respectively. Areas under the curve (AUC) calculated from
      concentration-time-curves with bioassay data are overestimated, because
      ciprofloxacin may be more active than enrofloxacin against E. coli 14 (ICB 4004)
      used in this test. Thus, pharmacokinetic parameters which are derived from AUC
      values are overestimated, too. Oral bioavailability calculated with bioassay
      results was more than 100% whereas availability of enrofloxacin was only 53%.
      Clearance was 10.3 ml/min.kg (antimicrobially active substance) and 27.1
      ml/min.kg (enrofloxacin). Elimination half life was 3.7 and 2.4 h, respectively.

PMID- 7801086
TI  - [Case report: persistent right aortic arch in a cat].

PMID- 7801087
TI  - [Vaccination of cats against infection with feline leukemia virus (FeLV): first
      recombinant vaccine and the effect of a pre-existing infection with feline
      immunodeficiency virus (FIV)].
AB  - A new recombinant FeLV vaccine was evaluated in 30 specified pathogen-free cats
      10 months of age cats. The vaccine consisted of the non-glycosylated FeLV
      envelope protein p45, aluminium hydroxide and a saponin adjuvant. The cats (n =
      18) were vaccinated twice intramuscularly, 3 weeks apart. All animals were
      challenged intraperitoneally with FeLV subgroup A, 18 weeks later. While 94% of
      the vaccinated cats showed no viraemia or were only transiently viraemic, 80% of
      the non-vaccinated animals became persistently viraemic within 2 to 3 weeks. In
      our hands the preventable fraction of the vaccine was 93%. In order to determine
      the effect of a pre-existing infection with feline immunodeficiency virus on the
      efficacy of vaccination, 50% of the cats were previously infected with FIV. The
      infected cats were protected to the same degree as the non-infected animals. With
      prolonged duration of FIV infection the probability increases, that the immune
      system of the cat will fail and clinical signs will appear. In order to observe a
      state of possible immunodeficiency, an accurate clinical examination of every cat
      prior to vaccination seems of major importance.

PMID- 7801088
TI  - [Volvulus of the proximal colon and the cecum in a dog].
AB  - Volvulus is the torsion of an organ around its pedicle (Garnier et al., 1990). In
      the dog, the volvulus of the stomach is well known, and the volvulus of the small
      intestine is rare (Carberry et al., 1989). Volvulus of the whole colon has been
      described once in a rough collie (Marks, 1986). Only two cases, both in great
      Danes, of torsion of the caecum and the proximal colon have been mentioned
      (Carberry et al., 1993). A third case, also in a great Dane, is thereafter
      described.

PMID- 7801089
TI  - Antimalarial transmission-blocking vaccines.
AB  - In the continuing efforts to develop strategies to limit the impact of malaria,
      scientists are constantly modifying established methods of vector control and
      antiparasite chemotherapy. Despite their best efforts malaria remains a major
      lethal and debilitating disease in the tropics annually killing 2 million
      children in Africa. New technologies have prompted the evaluation of vaccines as
      potentially powerful tools to ameliorate the impact of the parasite upon the
      infected human host, and more recently to block the transmission of the parasite
      from man to the mosquito vector. Laboratory studies suggest these transmission
      blocking vaccines may reduce transmission significantly and one candidate antigen
      is now being prepared for human trials. This article reviews the properties and
      merits of transmission-blocking vaccines; describes the various candidate
      antigens under development; raises questions that still need to be answered; and
      indicates some of the unexpected approaches that are now being considered in our
      attempts to control this important pathogen.

PMID- 7801090
TI  - Spore formation in Bacillus subtilis.
AB  - Bacillus subtilis is the best studied of the bacteria that make heat-resistant
      spores in response to starvation. The process of sporulation results in the
      formation of a cell type which is quite different in morphology from that of
      bacteria during normal growth. Sporulation requires the activation, in an ordered
      sequence, of many genes that are kept silent during vegetative growth. It also
      requires that these genes be activated differentially in two sister cells that
      are genetically identical. The sophisticated mechanisms responsible for both the
      temporal and the spatial regulation of gene expression are now understood in a
      fair amount of detail. They are likely to provide models which will make a
      valuable contribution to studies of development and differentiation in higher
      cells.

PMID- 7801091
TI  - Bacterial galvanotropism: mechanisms and applications.
AB  - Galvanotropism is the process by which a cell alters its shape to grow
      directionally in response to an electric field. This phenomenon is known for a
      wide variety of eukaryotic cells but the first report of bacterial galvanotropism
      appeared only recently. Escherichia coli, Enterobacter cloacae and (to a lesser
      extent) Bacillus subtilis curve rapidly and reversibly towards the anode of a
      uniform electric field. The mechanism for the response is not known but two
      observations permit a degree of speculation. Firstly, the anode-facing ends of
      cells elongate more rapidly than the cathode-facing ends of the same cells,
      suggesting that the field affects regional rates of wall synthesis and
      degradation. Secondly, the magnitude of the response depends on the extracellular
      pH, implicating anodal electrophoresis of membrane proteins in the mechanism. The
      ability of a field to modulate rates of wall growth locally can be exploited to
      investigate at least two fundamental, yet intractable, questions: the mechanism
      by which bacteria maintain non-spherical shapes and grow without bursting and the
      mechanism for the uniform segregation of DNA into daughter cells. Additionally,
      use of molecular biological techniques may permit identification of the molecular
      basis for galvanotropism, an approach that has not been feasible for most
      galvanotropic eukaryotic cells.

PMID- 7801092
TI  - [Functional properties of diagnostic ultrasound instruments. A concept of trial
      building blocks for implementing quality assurance].
AB  - Today's medical diagnostic ultrasonic devices are complex technical systems and
      need adequate Quality Assurance (QA) with regard to ultrasonic safety and
      performance. As to ultrasonic safety the International Declaration Standard IEC
      1157 issued in 1992 supports progress for design of future equipment. It will be
      increasing importance to connect and to balance out the requirements for acoustic
      safety and for the diagnostic potential of the equipment. In Germany the
      application of QA in ultrasonics has to consider limitations by structure.
      Against this background the author gives an overall view of QA for the
      performance of imaging and Doppler equipment. From recent technical and
      standardisation work expressing demands and solutions for QA derives a practical
      concept of a modular QA programme. As an example, the specific test steps and
      suitable instruments for the procedures are given for some QA programmes in B
      mode and Doppler-mode (B, cwD, pwD). A proposal is made how to split up the QA
      programme into a level 1 left to the medical personnel and a level 2 put to
      practical use by technical services or equipment distributors.

PMID- 7801093
TI  - [Effect of halothane anesthesia on cerebral blood flow velocity in children].
AB  - The effects of halothane on the cerebral circulation were studied in 23 children
      during general anaesthesia. Blood flow velocity in one middle cerebral artery was
      recorded continuously by transcranial Doppler sonography. Furthermore arterial
      blood pressure, pulse rate, endtidal CO2partial pressure and endtidal halothane
      concentration were recorded. Mean flow velocities/mean arterial blood pressures
      were 79 cm x s-1/65 mmHg; 86 cm x s-1/61 mmHg; 78 cm x s-1/54 mmHg and 67 cm x s
      1/48 mmHg with 1; 1.5; 2 and 2.5 per cent endtidal halothane concentrations,
      respectively. Endtidal CO2-partial pressure and pulse rate remained constant
      throughout the study. The higher cerebral blood flow velocities seen with 1.5 per
      cent halothane compared with 1 per cent can be explained by an increase in
      cerebral blood flow. The lower cerebral blood flow velocities and arterial blood
      pressure with 2.5 per cent halothane compared with 1.5 per cent indicate impaired
      cerebral autoregulation. However, cerebral blood flow appeared to be sufficient
      even with low arterial blood pressures.

PMID- 7801094
TI  - [Transesophageal echocardiography: indications and findings. Experiences from 3
      centers].
AB  - The introduction of transoesophageal echocardiography has greatly enhanced the
      noninvasive diagnostic possibilities in cardiology. This multicentre report
      analyses the findings in different indications as well as the rate of
      complications in 335 consecutive patients on whom transoesophageal
      echocardiography was performed. The most frequent indication was the search for a
      cardiac source of embolism (36%). Compared to patients with other indications,
      thrombi in the left atrial appendage, atrial septal aneurysms and protruding
      aortic atheromas were significantly more frequent in this group. Transoesophageal
      echocardiography was performed in 20% for the diagnosis of suspected endocarditis
      and vegetations and/or paravalvular abscesses could be demonstrated in 46% of
      these patients. Other important indications included the assessment of mitral
      valve disease, congenital heart disease, valve prosthesis dysfunction and aortic
      dissection. Clinically relevant complications occurred in 1.8% and were
      spontaneously reversible in all cases. Transoesophageal echocardiography is an
      extremely valuable and safe diagnostic tool in cardiology.

PMID- 7801095
TI  - [The value of various transcranial color doppler tests for determining
      cerebrovascular reserve capacity].
AB  - One of the techniques for the assessment of the cerebrovascular reserve capacity
      is the so-called "breath-holding" test. In order to minimise haemodynamic changes
      following deep inspiration the patients should hold their breath at the end of a
      normal inspiration. We studied three different ways (breath holding following
      normal inspiration [NI], deep inspiration [DI], hyperventilation [HV]), of
      performing this test in 20 healthy volunteers. The acetazolamide test was taken
      as a reference. The mean flow velocity (FVmean) in the middle cerebral artery was
      recorded continuously using a TCD monitoring system. Blood pressure, cardiac
      output and heart rate were measured simultaneously. Breath holding after deep
      inspiration resulted in longer apnoea (DI: 68.1 +/- 24.1 s; NI: 44.8 +/- 18.4 s;
      p < 0.01), produced the highest increase of FVmean (DI: +72.2 +/- 29.8%; NI:
      +69.2 +/- 29.0%) and was the least inconvenient to the patients. Following HV
      apnoea was longest (93.0 +/- 33.5 s; p < 0.01), but resulted in the lowest
      increase of FVmean were not significant. A significantly lower increase of FVmean
      (44.2 +/- 13.4%, p < 0.01 resp.) could be observed after intravenous injection of
      1 g acetazolamide. There were no significant haemodynamic changes in any case.
      Thus, this bedside test does not appear to be influenced by variations in breath
      holding.

PMID- 7801096
TI  - [Duplex ultrasound in diagnosis of visceral blood circulation].
AB  - Duplex sonography as a non-invasive technique to measure splanchnic and
      hepatoportal haemodynamics under physiological and pathophysiological conditions
      has recently attracted much attention. Determination of arterial and venous
      profiles enables reproducible pre- and postoperative flow estimations.
      Furthermore, this technique has harvested many interesting results in the
      complicating haemodynamic changes seen in patients with portal hypertension. The
      technique can even be considered as gold standard in the evaluation of flow
      changes in patients after orthotopic liver transplantation. This article reviews
      the use of duplex scanning in the splanchnic vascular bed.

PMID- 7801097
TI  - [Automated detection of microemboli in transcranial Doppler signals].
AB  - The detection of micro-emboli (ME) in the intracranial brain arteries by means of
      transcranial Doppler sonography depends on signal quality and on the definition
      of the detection levels. The qualitative analysis by ear should be replaced by
      quantitative measurement techniques to provide results that are cross-comparable
      to the ones of other studies. Algorithms for ME detection have been developed and
      implemented on a Doppler signal analyzer. Three quantitative criteria were
      established with test data. Tape recordings of 44 middle cerebral arteries from
      an ongoing study including patients before and after implantation of prosthetic
      heart valves were examined. The data were first corrected for frequency response,
      phase and amplitude and examined by two independent investigators and by the
      instrument. Within the 44 measurements both examinations by ear found the same 26
      samples to contain zero audible ME signals. The instrument detected in 21 cases
      zero ME signals, in 4 cases 1 signal and in 1 case 4 signals. For 18 tapes the
      ear-method provided counts of 1 to 160 ME's. In 12 cases the two investigators
      got the same result, in the remaining 6 cases the higher of both figures was
      selected for comparison to the automated count. The counting by the instrument
      was exactly the same for 7 cases, in 7 cases the instrument counted more, in 4
      cases it detected fewer ME signals compared to the reference. The method and the
      proposed detection criteria provided more false positive than false negative
      results. This appeared to be due to artifact detection and on higher resolution
      in time leading to better separation of double events compared to the ear method.
      Assuming an adequate quality of the quadrature signals, the method may lead to
      automatic screening for ME signals.

PMID- 7801098
TI  - [Acceptance of electronic data processing supported documentation of ultrasound
      findings in routine clinical practice. A survey].
AB  - We carried out a survey to determine the acceptance of the ultrasound
      documentation software, CUBUS, in clinical practice. Since August 1, 1988, CUBUS,
      versions V1.01 to V2.02 has been employed in clinical routine. By October 1991
      10,850 reports had been stored in version 2.02. The software is installed on a
      personal computer (Siemens PCD-2, 40MB, 640 KB RAM) to which a laserprinter is
      connected. The work of operating the system is shared between the nursing and
      medical staff. In order to investigate the acceptance of the printed reports
      produced with this system, we carried out a poll among the physicians working at
      the hospital. Among the 86 physicians who receive 95% of the US reports, 58% (n =
      50) responded. On the basis of the categories good, satisfactory, adequate and
      poor, we requested an assessment of layout, presentation, comprehension,
      completeness and overall impression. The overall impression was assessed as good
      or satisfactory in 34% and 42%, respectively. In the case of the individual
      criteria (see above), the categories good and satisfactory scored 62% and 34%,
      58% and 32%, 68% and 18% and 72% and 24%, respectively. The terminology used was
      accepted by 84%. Addition of, for example, image documentation, and
      endosonography, will expand the advantages of the input of findings and further
      improve the good overall impression made by the report printout in our survey, so
      that the relatively long input time requirement accounting for some 30% of the
      total examination time, is accordingly justified.

PMID- 7801099
TI  - [A versatile phantom for hemodynamic measurements with ultrasound Doppler
      equipment].
AB  - The test object described comprises a blood simulating liquid pumped through
      tubes embedded in tissue-mimicking material. The main components of the system
      can be realised in different ways. They are largely exchangeable with each other.
      Water, reticulated foam or silicone rubber is used as bulk background material,
      blood vessels are simulated using latex or silicone tubes or heat-shrink
      sleeving; in the artificial blood, sephadex particles or silicone emulsion were
      used as scatterers. The suspension of scattering particles is driven by a roller
      pump or a membrane dosage pump. The features of the components are described and
      the applications of the different phantoms discussed.

PMID- 7801100
TI  - [Ultrasound image of an echinococcus daughter cyst in the gallbladder].
AB  - By the case presented, which is a clear example of a daughter cyst of an
      echinococcus in the gall bladder lumen, we have extended our knowledge of the
      possibility of ultrasound for demonstration of abdominal pathology. Besides the
      well-known sonographic picture of the liver echinococcus, we now know that we are
      in certain cases in a position to represent also the echinococcus daughter cyst
      in the biliary tree. Characteristic is its annular pattern. In cases like this
      one, we give ultrasound preference over the ERCP and CT.

PMID- 7801101
TI  - [Comment on an epidemiologic study of the safety of ultrasound].

PMID- 7801102
TI  - Male breast cancer: three case reports and review of the literature.
AB  - Carcinoma of the breast occurs so infrequently in men that it is not at al well
      known either to patients or physicians. The causes of breast cancer in men are
      unknown. The most common clinical manifestation of breast cancer in men is a
      painless, firm subareolar mass or a mass in the upper outer quadrant of the
      breast. Diagnosis can be confirmed by fine-needle aspiration or surgical biopsy.
      Infiltrating ductal carcinoma is the predominant histologic type. After primary
      surgical treatment, men with axillary lymph node metastasis should receive
      adjuvant systemic chemotherapy. The use of radiation therapy for local control of
      the disease is recommended if there is invasion of the chest wall. Because most
      men with carcinoma of the breast have estrogen and progesterone-receptor positive
      tumors, breast cancer in men is likely to respond to hormonal manipulation.

PMID- 7801103
TI  - The physician as role model.

PMID- 7801104
TI  - Survival of the tiny neonate: USD School of Medicine/Sioux Valley Hospital
      experience, 1981-1992.
AB  - The survival of very low birth weight newborn infants of < or = 1000 gms cared
      for in the University of South Dakota School of Medicine/Sioux Valley Hospital
      Neonatal Intensive Care Unit was analyzed for the 12 year period of 1981-1992.
      Survival has increased from 45% in 1981-1983 to 65% in 1990-1992. The most recent
      figures for 1990-1992 indicate 54% survival in neonates of < or = 600 gms, 73% in
      those of 601-700 gms, 56% in those of 701-800 gms, 60% in those of 801-900 gms
      and 81% in those of 901-1000 gms. Survival rates by birth weight and gestational
      age are comparable to nationally published statistics. The potential for normal
      long term outcome, including physical growth and intellectual development,
      appears to be very good, with 74% of long term survivors having no evidence of
      severe physical or neurologic impairment at the time of discharge from the
      hospital.

PMID- 7801105
TI  - Strontium-90 concentrations in human teeth in south Ukraine, 5 years after the
      Chernobyl accident.
AB  - Approximately 1000 human teeth, collected in South Ukraine, in 1990-1991, were
      measured for 90Sr concentration. The teeth were grouped into 18 samples according
      to the age and sex of the donors. Measured levels of 90Sr concentrations were
      lower by a factor of 10 than measurements taken in the mid-1960s and mid-1970s.
      An interesting feature of the data is a 3-fold enhancement of contamination
      levels in the 25-45 year-old age group of the male population. A possible
      explanation for this anomaly is that this age group contains a significant number
      of men who were mobilized immediately after the Chernobyl accident for clean-up
      operations within the 30-km zone around the damaged nuclear power plant.

PMID- 7801106
TI  - Characteristics of airborne microfungi in subtropical homes.
AB  - Because of high relative humidity (60-90%) and mild temperature (15-37 degrees C)
      all year round, fungi grow more quickly and easily in Taiwan, a subtropical
      country. Field evaluations of airborne fungi indoors and outdoors in two major
      types of cities (Taipei and Tai-Chi) in Taiwan were conducted during the fungus
      concentration peak season. Two-stage Andersen culture plate impactors were used
      to determine the number concentrations, genus and respirable fraction of indoor
      and outdoor fungi. The geometric mean concentrations of indoor and outdoor fungi
      in these two areas were found to be > 1000 colony forming units (CFU) m-3. In
      addition, Aspergillus, Penicillium, Cladosporium and yeast were observed to be
      dominant and their number concentrations in some homes exceeded 1000 CFU m-3.
      Moreover, the indoor and outdoor concentrations of the abundant fungi were found
      to be moderately correlated.

PMID- 7801107
TI  - Ozone formation in the greater Cairo area.
AB  - Ozone formation in the greater Cairo area was studied in 1990 in a 3-week
      measurement period performed at three sites (Shoubra El-Kheima, Mokattam Hill,
      Helwan), covering a north-south direction of 27 km, and in 1991, from the
      beginning of April until the end of October, by measurement of the seasonal
      variation of ozone at one site at El-Kobba. The sinusoidal shape in the diurnal
      volume fraction plots with peak values of 120 ppb and daily mean value of 50 ppb
      throughout the year indicate a substantial contribution of photochemistry to the
      ozone content of the atmosphere. Ozone is produced predominantly over the
      industrial area in the north and in the centre of Cairo and transported southward
      by the prevailing northerly winds. Contrary to many urban areas in Europe and in
      North America, fairly high average ozone levels of 40 ppb are observed during the
      night throughout the spring and the summer. This may imply that health hazards
      and crop damage are higher in the greater Cairo area than in Central Europe.

PMID- 7801108
TI  - Development and validation of an air-to-beef food chain model for dioxin-like
      compounds.
AB  - A model for predicting concentrations of dioxin-like compounds in beef is
      developed and tested. The key premise of the model is that concentrations of
      these compounds in air are the source term, or starting point, for estimating
      beef concentrations. Vapor-phase concentrations transfer to vegetations that
      cattle consume, and particle-bound concentrations deposit onto soils and these
      vegetations as well. Congener-specific bioconcentration parameters, coupled with
      assumptions on cattle diet, transform soil and vegetative concentrations into
      beef fat concentrations. The premise of the validation exercise is that a profile
      of typical air concentrations of dioxin-like compounds in a United States rural
      environment is an appropriate observed independent data set, and that a
      representative profile of United States beef concentrations of dioxin-like
      compounds is an appropriate observed dependent result. These data were developed
      for the validation exercise. An observed concentration of dioxin toxic
      equivalents in whole beef of 0.48 ng/kg is compared with a predicted 0.36 ng/kg.
      Principal uncertainties in the approach are identified and discussed. A major
      finding of this exercise was that vapor phase transfers of dioxin-like compounds
      to vegetations that cattle consume dominate the estimation of final beef
      concentrations: over 80% of the modeled beef concentration was attributed to such
      transfers.

PMID- 7801109
TI  - Accumulation of cadmium associated with sewage sludge by a marine amphipod
      crustacean.
AB  - Cadmium bound to sewage sludge (5% mixture with littoral mud) is available to the
      deposit-feeding marine amphipod crustacean Corophium volutator (Pallas). The
      amphipod accumulates labelled cadmium from sludge in proportion to both duration
      of exposure and cadmium concentration of the sludge. Newly accumulated cadmium is
      added onto the existing cadmium body load without significant excretion. Thus,
      cadmium in association with sewage sludge dumped at sea may be absorbed and
      accumulated by deposit-feeding invertebrates, with the potential of being
      transferred along marine food chains.

PMID- 7801110
TI  - Heavy metals in human hair samples from Austria and Italy: influence of sex and
      smoking habits.
AB  - Hair samples from 79 young healthy adults from Vienna (Austria) and Rome (Italy)
      were analyzed for As, Cd, Co, Cr, Ni and Pb by ICP-MS. No differences were found
      between the two locations except for chromium, which was significantly higher in
      the Viennese population (P < 0.001). In both cities male hair contained higher
      arsenic (P < 0.001) and lower cadmium (P < 0.05) levels than female hair, and in
      Vienna lead concentrations were lower in males (P < 0.05). Striking differences
      appeared when smokers were compared with non-smokers. Geometric means
      (micrograms/g) of smokers versus non-smokers were: arsenic 0.081 vs. 0.065,
      cadmium 0.075 vs. 0.038 (P < 0.05), cobalt 0.025 vs. 0.010 (P < 0.05), chromium
      0.84 vs. 0.72 (P < 0.05), lead 3.42 vs. 1.47 (P < 0.001) and nickel 0.64 vs. 0.32
      (P < 0.005). Consideration of a large number of biological and behavioural
      factors minimizes bias inherent in unmatched sample composition.

PMID- 7801111
TI  - Environmental health aspects of lubricant additives.
AB  - This paper describes briefly the industrial hygiene aspects of the manufacture
      and use of lubricant additives and gives some details concerning the acute,
      chronic and environmental toxicity of important additive types. It also addresses
      the need to communicate information about product hazards and draws attention to
      some special points of concern which the additives industry in general has with
      existing and developing environmental health regulations. Finally, it takes a
      crystal ball to the long-term future of additives manufacture.

PMID- 7801112
TI  - Health, safety and environmental aspects of used crankcase lubricating oils.
AB  - This paper indicates the health, safety and environmental concerns which have
      been expressed regarding the handling, re-use and disposal of used crankcase
      lubricating oils and discusses the factors which are believed to these concerns.
      It also indicates the current and developing situation with regard to legislation
      in this area, discusses briefly the disposal of used oils in cement kilns and
      sets out the views of the industry sectors most involved. Finally, it describes
      the simple safeguards the adoption of which should enable these materials to be
      handled with a high degree of safety.

PMID- 7801113
TI  - Mercury concentrations in marine species from the coastal area of Tarragona
      Province, Spain. Dietary intake of mercury through fish and seafood consumption.
AB  - A total of 592 samples of 21 species of fish, cephalopods, crustaceans and
      molluscs were analyzed for mercury concentrations between November 1992 and
      February 1993 at four sites on the Tarragona coast in Catalonia, Spain. The
      results of this study show that mercury discharges into the marine environment of
      Tarragona Province have increased the mercury content of marine organisms, with
      fish and crustaceans being the groups which accumulated the highest levels of
      this element. In a subsequent study, the individual dietary intake of mercury
      from fish and seafood consumption by the population of Tarragona Province was
      estimated to be 16 micrograms day-1. This intake of mercury would not signify a
      health hazard for consumers of fish and seafood from the Tarragona coastal
      waters.

PMID- 7801114
TI  - Molecule of the year: the DNA repair enzyme.

PMID- 7801115
TI  - DNA repair works it works its way to the top.

PMID- 7801116
TI  - PCR products and CITES.

PMID- 7801117
TI  - FBI says sting nabs biotech spies.

PMID- 7801118
TI  - Oncogenes reach a milestone.

PMID- 7801119
TI  - HIV integrase structure catalyzes drug search.

PMID- 7801120
TI  - Mechanisms of DNA excision repair.

PMID- 7801121
TI  - Transcription-coupled repair and human disease.

PMID- 7801122
TI  - Mismatch repair, genetic stability, and cancer.

PMID- 7801123
TI  - Reconstitution of transcription factor SL1: exclusive binding of TBP by SL1 or
      TFIID subunits.
AB  - RNA polymerase I and II transcription factors SL1 and TFIID, respectively, are
      composed of the TATA-binding protein (TBP) and a set of TBP-associated factors
      (TAFs) responsible for promoter recognition. How the universal transcription
      factor TBP becomes committed to a TFIID or SL1 complex has not been known.
      Complementary DNAs encoding each of the three TAFIs that are integral components
      of SL1 have not been isolated. Analysis of subunit interactions indicated that
      the three TAFIs can bind individually and specifically to TBP. In addition, these
      TAFIs interact with each other to form a stable TBP-TAF complex. When TBP was
      bound first by either TAFI110, 63, or 48, subunits of TFIID such as TAFII250 and
      150 did not bind TBP. Conversely, if TBP first formed a complex with TAFII250 or
      150, the subunits of SL1 did not bind TBP. These results suggest that a mutually
      exclusive binding specificity for TBP intrinsic to SL1 and TFIID subunits directs
      the formation of promoter- and RNA polymerase-selective TBP-TAF complexes.

PMID- 7801124
TI  - Crystal structure of the catalytic domain of HIV-1 integrase: similarity to other
      polynucleotidyl transferases.
AB  - HIV integrase is the enzyme responsible for inserting the viral DNA into the host
      chromosome; it is essential for HIV replication. The crystal structure of the
      catalytically active core domain (residues 50 to 212) of HIV-1 integrase was
      determined at 2.5 A resolution. The central feature of the structure is a five
      stranded beta sheet flanked by helical regions. The overall topology reveals that
      this domain of integrase belongs to a superfamily of polynucleotidyl transferases
      that includes ribonuclease H and the Holliday junction resolvase RuvC. The active
      site region is identified by the position of two of the conserved carboxylate
      residues essential for catalysis, which are located at similar positions in
      ribonuclease H. In the crystal, two molecules form a dimer with a extensive
      solvent-inaccessible interface of 1300 A2 per monomer.

PMID- 7801125
TI  - A receptor component of the chloroplast protein translocation machinery.
AB  - The chloroplast outer envelope protein OEP86 functions as a receptor in precursor
      protein translocation into chloroplasts. Sequence analysis suggests that the
      precursor of OEP86 is directed to the chloroplast outer envelope by a cleavable,
      negatively charged, and unusually long amino-terminal peptide. This presequence
      is unlike other potential targeting signals and suggests the existence of another
      membrane insertion pathway. Insertion of precursor OEP86 required the hydrolysis
      of adenosine triphosphate and the existence of surface exposed chloroplast
      membrane components, and it was not competed by another precursor protein
      destined for the internal plastid compartments.

PMID- 7801126
TI  - Fatty acylation of two internal lysine residues required for the toxic activity
      of Escherichia coli hemolysin.
AB  - Hemolysin of Escherichia coli is activated by fatty acylation of the protoxin,
      directed by the putative acyl transferase HlyC and by acyl carrier protein (ACP).
      Mass spectrometry and Edman degradation of proteolytic products from mature toxin
      activated in vitro with tritium-labeled acylACP revealed two fatty-acylated
      internal lysine residues, lysine 564 and lysine 690. Resistance of the acylation
      to chemical treatments suggested that fatty acid was amide linked. Substitution
      of the two lysines confirmed that they were the only sites of acylation and
      showed that although each was acylated in the absence of the other, both sites
      were required for in vivo toxin activity.

PMID- 7801127
TI  - Coordinate initiation of Drosophila development by regulated polyadenylation of
      maternal messenger RNAs.
AB  - Pattern formation in Drosophila depends initially on the translational activation
      of maternal messenger RNAs (mRNAs) whose protein products determine cell fate.
      Three mRNAs that dictate anterior, dorsoventral, and terminal specification-
      bicoid, Toll, and torso, respectively--showed increases in polyadenylate
      [poly(A)] tail length concomitant with translation. In contrast, posteriorly
      localized nanos mRNA, although also translationally activated, was not regulated
      by poly(A) status. These results implicate at least two mechanisms of mRNA
      activation in flies. Studies with bicoid mRNA showed that cytoplasmic
      polyadenylation is necessary for translation, establishing this pathway as
      essential for embryogenesis. Combined, these experiments identify a regulatory
      pathway that can coordinate initiation of maternal pattern formation systems in
      Drosophila.

PMID- 7801128
TI  - Binding and stimulation of HIV-1 integrase by a human homolog of yeast
      transcription factor SNF5.
AB  - Upon entry into a host cell, retroviruses direct the reverse transcription of the
      viral RNA genome and the establishment of an integrated proviral DNA. The
      retroviral integrase protein (IN) is responsible for the insertion of the viral
      DNA into host chromosomal targets. The two-hybrid system was used to identify a
      human gene product that binds tightly to the human immunodeficiency virus-type 1
      (HIV-1) integrase in vitro and stimulates its DNA-joining activity. The sequence
      of the gene suggests that the protein is a human homolog of yeast SNF5, a
      transcriptional activator required for high-level expression of many genes. The
      gene, termed INI1 (for integrase interactor 1), may encode a nuclear factor that
      promotes integration and targets incoming viral DNA to active genes.

PMID- 7801129
TI  - ATP-dependent nucleosome reconfiguration and transcriptional activation from
      preassembled chromatin templates.
AB  - GAL4-VP16-mediated nucleosome reconfiguration and transcriptional activation were
      observed with preassembled chromatin templates that contained regular and
      physiological nucleosome spacing. Both processes were dependent on adenosine
      triphosphate (ATP), although binding of GAL4-VP16 to the chromatin was ATP
      independent. Factor-mediated nucleosome reconfiguration was not, however,
      sufficient for transcriptional activation. These experiments recreate in vitro
      the active participation of nucleosomal cores in the regulation of transcription
      that occurs in vivo, and they suggest a multistep pathway for transcriptional
      activation in which factor- and ATP-dependent nucleosome reconfiguration is
      followed by facilitation by the DNA-bound activator of transcription from the
      repressed chromatin template.

PMID- 7801130
TI  - Assembly of transcriptionally active RNA polymerase I initiation factor SL1 from
      recombinant subunits.
AB  - Initiation of ribosomal RNA synthesis by RNA polymerase I requires the promoter
      selectivity factor SL1, which consists of the TATA-binding protein, TBP, and
      three associated factors, TAFIS 110, 63, and 48. Here the in vivo and in vitro
      assembly of functional SL1 complexes from recombinant TAFIS and TBP are reported.
      Complexes containing TBP and all three TAFIS were as active in supporting
      transcription from the human ribosomal RNA gene promoter as endogenous SL1,
      whereas partial complexes without TBP did not efficiently direct transcription in
      vitro. These results suggest that TAFIS 110, 63, and 48, together with TBP, are
      necessary and sufficient to reconstitute a transcriptionally active SL1 complex.

PMID- 7801132
TI  - Polymerase structures and mechanism.

PMID- 7801131
TI  - An all D-amino acid opioid peptide with central analgesic activity from a
      combinatorial library.
AB  - A synthetic combinatorial library containing 52,128,400 D-amino acid hexapeptides
      was used to identify a ligand for the mu opioid receptor. The peptide, Ac-rfwink
      NH2, bears no resemblance to any known opioid peptide. Simulations using
      molecular dynamics, however, showed that three amino acid moieties have the same
      spatial orientation as the corresponding pharmacophoric groups of the opioid
      peptide PLO17. Ac-rfwink-NH2 was shown to be a potent agonist at the mu receptor
      and induced long-lasting analgesia in mice. Analgesia produced by
      intraperitoneally administered Ac-rfwink-NH2 was blocked by
      intracerebroventricular administration of naloxone, demonstrating that this
      peptide may cross the blood-brain barrier.

PMID- 7801133
TI  - Siliconosis: a spectrum of illness.

PMID- 7801134
TI  - Silicone toxicology.
AB  - Silicone, a man-made polymer containing the element silicon, has been used in a
      variety of medical devices including breast implants. Silicone was used, in part,
      because it was suggested to have the property of biological inertness. Inert
      materials do not affect chemical, physiological, or immunological processes.
      Silicone is not inert. Silicone from breast implants "bleeds" through the
      surrounding envelope and is present in the surrounding capsule or migrates to
      other distant locations. Silicone and/or the multiple chemical contaminants
      elicit foreign body reactions associated with granulomatous inflammation and
      fibrosis. Silicone and its contaminants have the potential for significant
      toxicity in the implant recipient.

PMID- 7801135
TI  - A pathophysiological examination of the biophysics and bioreactivity of silicone
      breast implants.
AB  - Historically, silicones have been considered biologically inert materials, and
      have therefore been used widely in a variety of medical applications. Recently,
      controversy has arisen concerning the bioreactivity of silicone; reports of
      adverse inflammatory and immunological complications that may be evoked by
      silicone breast implants have appeared in the medical literature and have
      received great attention from the lay press. The phenomena said to be associated
      with silicones may be attributed pathophysiologically to the inherent surface
      activity of silicone. The human body's initial response to the silicone of breast
      implants is the adsorption of various plasma proteins, including clotting and
      complement proteins, to the implant surface. Other macromolecules in the
      biological milieu may follow. The conformational integrity of this adsorbed
      macromolecular layer affects much of the subsequent biological reaction.
      Clinically silent inflammation, locally significant inflammation, inflammation
      with constitutional symptoms, and inflammation with immunological activation are
      possible consequences.

PMID- 7801136
TI  - Clinical findings in symptomatic women with silicone breast implants.
AB  - We report the clinical findings in a series of women with silicone breast
      implants (SBI) and rheumatic disease. These findings represent the first 50
      patients seen at the University of South Florida Medical Clinic between March
      1977 and January 1991. The average age was 44 years with a range of 30 to 66
      years. The most common clinical findings included chronic fatigue, muscle pain,
      joint pain, joint swelling, and lymphadenopathy. Seventeen women with an average
      Steinbrocker functional class of 1.8 decided not to remove the implants. An
      average of 14 months later, follow-up showed no change in their condition. Thirty
      three women, with an average functional class of 2.5 underwent implant removal.
      Twelve of the 33 had documented implant rupture. During an average follow-up of
      22 months after implant removal, 24 women improved clinically, 8 did not change,
      and 1 worsened. We believe this series supports a relationship between silicone
      breast implants and rheumatic disease signs and symptoms. Although this report is
      not a definitive epidemiological study, findings suggest that physicians should
      inform women about the possible benefit of implant removal.

PMID- 7801137
TI  - A clinical and laboratory profile of symptomatic women with silicone breast
      implants.
AB  - One hundred seventy-six patients with breast prosthetic implants were evaluated.
      All women were symptomatic and were referred by either attorneys (152) or
      physicians (24) for rheumatic evaluation. The women ranged in age from 24 to 72
      with a mean of 45 years. Indications for surgery were cosmetic (128), cancer
      (34), and other (14). Implants had been in place for 7 years or more in 120
      patients and < 2 years in only 8. Eighty-three women required explantation of
      their original prostheses, and 63 had new implants inserted of which 47 were
      silicone and 16 were saline. Capsular contractures were present in 128 women, and
      documented implant rupture occurred in 67. Sixty-four women underwent manual
      closed capsulotomies. Of the 63 revisions, 37 resulted in contractures of the new
      implant. The most frequent symptoms seen in the women were chronic fatigue (77%)
      cognitive dysfunction (65%), arthralgia (56%), dry mouth (53%), dry eye (50%),
      alopecia (40%), and dysphagia (35%). The most common findings on physical
      examination were telangiectasias (60%), erythema of the chest wall (56%), carpal
      tunnel syndrome (47%), petechiae (46%), lacrimal gland enlargement (26%), thyroid
      tenderness (22%), thyroid enlargement (21%), and parotid enlargement (18%).
      Laboratory findings included elevated cholesterol (59%), elevated erythrocyte
      sedimentation rate (32%), elevated serum immunoglobulin (28%), and positive
      autonuclear antibody (25%) seen most often. Despite clinical features suggesting
      Sjogren's syndrome, antibodies to Ro (SSA) were seen in only 2 patients, and
      antibodies to La (SSB) were seen in only 4 patients. Siliconosis is a novel
      systemic disease with symptoms of chronic fatigue, cognitive dysfunction, sicca
      syndrome, and arthralgia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7801138
TI  - Epidemiology of silicone-related disease.
AB  - The epidemiology of silicone-related disease (SRD) is complicated by the variety
      of disease endpoints that have been associated with silicone exposure and the
      atypical nature of these diseases in silicone-exposed women. Current research
      reviewed here suggests that SRD may constitute a new disease entity, thus
      complicating disease definition and rendering studies of classic disease unlikely
      to detect risks of silicone exposure. This report addresses the most important
      study design issues (disease and exposure definitions, bias, confounding, and
      power) in the context of studies of SRD. The variety of silicones used
      complicates the definition of exposure for all studies, and for some populations
      simply determining who was implanted will be difficult. For any of these studies,
      inadequate patient follow-up is likely to underestimate disease risk. Studies of
      SRD are also complicated by confounding. That is, whether or not a woman chooses
      to receive an implant is related to her age, race, and other variables also
      related to rheumatoid and autoimmune disease. The absence of an appropriate
      control group also plaques published studies of silicone-related disease.
      Finally, inadequate sample size, resulting in studies of low statistical power,
      is a critical problem for rare diseases such as SRD. These points are illustrated
      using two published studies and five studies in progress.

PMID- 7801139
TI  - A profile of symptomatic patients with silicone breast implants: a Sjogrens-like
      syndrome.
AB  - Exposure of breast tissue to silicone has been associated with autoimmune
      diseases in the medical literature since the 1960's. Japanese women injected with
      raw silicone had features of a collagen vascular disease but did not meet
      criteria for a specific diagnosis. Subsequently, we have seen women with silicone
      breast implants that have similar problems. We performed a prospective
      noncontrolled study on women with silicone breast implants. Results from the
      first 50 consecutive women revealed the most prominent complaints in this group
      were fatigue (89%), generalized stiffness (75%), poor sleep (71%), and
      arthralgias (78%). Other problems included Raynaud's phenomenon, alopecia,
      adenopathy, night sweats, and frequent sore throats. Unexpectedly, half of these
      women complained of dry eyes and dry mouths. Positive antinuclear antibodies and
      or rheumatoid factors were discovered in 38% of patients although the anti-SSA
      antibody was found in only one patient and anti-SSB in none. Labial salivary
      gland biopsies in 5 cases showed mononuclear cell infiltrates compatible with
      Sjogren's syndrome in 4. The infiltrating cells were predominantly CD68 positive
      monocyte/macrophages, which is different from what is found in Sjogren's
      syndrome. These findings may indicate the presence of a unique syndrome
      associated with silicone implants that is characterized by musculoskeletal pain
      and autoimmune features.

PMID- 7801140
TI  - Autoantibodies in patients with silicone implants.
AB  - Immune disorders are characterized by development of autoantibodies.
      Autoantibodies, particularly antinuclear antibodies, are detected in the majority
      of patients with connective tissue diseases such as systemic lupus erythematosus
      and scleroderma. Recent reports have described persons with silicone implants who
      have developed scleroderma and systemic lupus erythematosus. Since autoantibodies
      are suspected to play an important role in the pathogenesis of the connective
      tissue disease, the nature of the autoantibodies produced in patients with
      silicone-associated rheumatic disease is important to understand. A review of the
      English literature and abstracts from the 1992 American College of Rheumatology
      meeting showed that immunofluorescent testing for antinuclear antibody was
      positive in a wide range (7% to 68%) of patients with silicone implants. When
      examining only those patients with silicone implants and clinical evidence of
      connective tissue disease, the proportion of patients with a positive
      immunofluorescent test was less than commonly found in a series of patients with
      idiopathic connective tissue disease. Sensitive testing by Western blot technique
      revealed autoantibodies in 10% of patients with silicone implants and negative
      immunofluorescent test results. Patients with silicone implants and scleroderma
      like illness were characterized by anticentromere and anti-PM-Scl antibodies,
      whereas patients with silicone implants and SLE or undifferentiated connective
      tissue disease were characterized by antibodies to small nuclear
      ribonucleoproteins, specifically B'/B polypeptide. In addition, antibodies to a
      high molecular weight protein have been discovered by Western blot in more than
      50% of persons with silicone implants. Differences in autoantibody production
      between patients with silicone-associated rheumatic disease and patients with
      idiopathic rheumatic disease may be a distinguishing feature. Further
      characterization of these autoantibodies is needed.

PMID- 7801141
TI  - Silicone breast prostheses implantation and explanation.
AB  - Breast implants have been used for augmentation and reconstruction for a 30-year
      period. Standard techniques have been used for the successful placement of
      mammary prostheses to enhance or replace breast tissue. All breast implants are
      surrounded by a capsule. The most common complication of breast implant surgery
      is hardening and contracture of the capsule. Explanation of implants is indicated
      for implant rupture, infection, extrusion, siliconoma, breast pain, painful
      capsular contracture, malposition, significant patient fear, and systemic
      symptoms thought secondary to implants. A number of alternatives are available
      for postexplant reconstruction, including myocutaneous flaps and free tissue
      transfers.

PMID- 7801142
TI  - Clinical relevance of granulocyte-macrophage colony-stimulating factor.

PMID- 7801143
TI  - Granulocyte-Macrophage Colony Stimulating Factor: Current Knowledge and
      Perspectives of a New Growth Factor. Proceedings of a symposium. Cologne,
      Germany, March 1993.

PMID- 7801144
TI  - High-dose therapy and autografting with peripheral blood stem cells in malignant
      lymphoma: granulocyte-macrophage colony-stimulating factor for stem cell
      mobilization.

PMID- 7801145
TI  - Experimental basis for the use of recombinant human granulocyte-macrophage colony
      stimulating factor in patients with acute myeloid leukemia.
AB  - Granulocyte-macrophage colony-stimulating factor (GM-CSF) not only stimulates
      hematopoiesis, but also induces the proliferation and differentiation of leukemic
      myeloid cells. The observation that clonogenic growth of malignant cells can be
      induced in vitro has led to the development of therapeutic concepts that aim to
      increase the sensitivity of cells to cytostatic and cytotoxic agents by priming
      them with GM-CSF. In in vitro experiments, preincubating leukemic cells with
      recombinant cytokines including GM-CSF led to a consistent, dose-dependent
      increase in the cytotoxicity of cytosine arabinoside (Ara-C). This effect has
      since been observed in patients with acute myeloid leukemia (AML) although its
      mechanism is not yet entirely clear. It seems that GM-CSF increases the relative
      number of cells in the S phase of the cell cycle and enhances the activity of DNA
      polymerases, enzymes that are essential to nucleotide incorporation into DNA.
      Based on these experimental results, numerous clinical trials have investigated
      the role of GM-CSF in priming leukemic blasts before chemotherapy. These studies
      will allow us to determine whether our in vitro observations of increased
      cytotoxicity translate into higher remission rates and durations, and will help
      us to identify the patient subgroups most likely to benefit from this therapeutic
      approach.

PMID- 7801146
TI  - Rationale for the use of granulocyte-macrophage colony-stimulating factor in
      oncology.

PMID- 7801147
TI  - Granulocyte-macrophage colony-stimulating factor in the treatment of small cell
      lung cancer.

PMID- 7801148
TI  - The role of granulocyte-macrophage colony-stimulating factor in the treatment of
      germ cell tumors. German Testicular Cancer Study Group.
AB  - Hematopoietic growth factors, such as granulocyte-macrophage colony-stimulating
      factor (GM-CSF), may gain increasing importance in the treatment of patients with
      malignant germ cell tumors. For patients with far advanced testicular cancer, who
      only have a chance of long-term cure in the range of 40% to 50% by standard
      induction chemotherapy, the German Testicular Cancer Study Group has shown that
      the application of GM-CSF after PEI chemotherapy has allowed the increase of dose
      intensity of this three-drug regimen by a factor of 1.4. In 75 evaluable patients
      an overall survival rate of 79% after a median follow-up of 27 months was
      achieved. The dose-limiting toxicity of this stepwise dose escalation protocol of
      the PEI regimen was severe mucositis/enteritis (World Health Organization [WHO]
      degrees 3/degrees 4) in 33% of the patients and prolonged thrombocytopenia (<
      20,000/microL for more than 10 days). In future trials, hematopoietic growth
      factors will be used in the treatment of far-advanced testicular cancer to
      generate peripheral blood stem cells (PBSC) that can be used to overcome both
      granulocytopenia and thrombocytopenia. This approach with the use of PBSC and
      hematopoietic growth factors will allow us to apply multiple cycles of up-front
      dose-intensified PEI chemotherapy in this unfavorable subgroup of patients.
      However, with the establishment of an optimal hematopoietic support in these
      studies, the value of dose-intensified chemotherapy in advanced testicular cancer
      will have to be tested against standard dose regimens in prospective randomized
      trials.

PMID- 7801149
TI  - XIIIth International Conference on the Social Sciences and Medicine.
      Balatonfured, Hungary, 10-14 October 1994. Proceedings.

PMID- 7801150
TI  - Beyond the orthodox: heresy in medicine and social science.
AB  - Kuhn's seminal work on scientific revolutions has undermined any strong claim to
      the idea that there is one single true theory about the way nature is. Both
      social science and medicine share, in differing ways, the uncertainty produced by
      the complexity of the human condition. This is not well accommodated by the
      traditional medicine model. There are both individual diseases and individual
      responses to disease that require a more holistic response to the patient. The
      holistic responses to these problems show promise but require careful evaluation
      through critical reflection on our practice of medicine.

PMID- 7801151
TI  - The dynamics of heresy in a profession.
AB  - It has been suggested that the term 'heresy' be rehabilitated to describe
      challenges to ideology in a profession. However, the term has been used in a
      variety of ways, impairing its descriptive utility. Using a variety of examples
      of potential heretical ideas in modern science and medicine, this paper tries to
      carefully define heresy and distinguish it from other forms of ideological
      challenge to a profession, such as challenges to knowledge products and
      challenges to authority. A dramaturgical approach is then used to try and
      describe the stages of heretical conflict in a profession.

PMID- 7801152
TI  - The cultural and philosophical foundations of normative medical ethics.
AB  - Thirty years ago, the idea that culture and philosophy could provide a foundation
      for normative medical ethics was more easily entertained than it is today when
      the very notion of a norm, whether culturally, philosophically or ethically
      derived, is in itself a problem. In large measure this comes from our
      contemporary embrace of cultural and philosophical pluralism and an increasing
      tendency to exchange the difficult belief in abstract and universally applicable
      norms for the more accessible notion that ethical values are cultural and
      relative derivatives. Despite this, in the face of the unprecedented ethical
      dilemmas presented by modern medicine, we have attempted to apply traditional
      ethical norms and analysis to modern medicine to establish a consensus for its
      right practice. Unfortunately, the attempt has not been successful, so that
      wherever we turn we find that ethical problems in medicine remain intractable and
      unresolved. That, in turn, has prompted a certain scepticism about the efficacy
      of ethics in medicine. In order to understand why we have reached this impasse,
      it is essential to realize that we have seriously underestimated the way science
      and technology have informed and, as a consequence, transformed the practice of
      medicine. Contributing to this, our tendency to think of technology simply as a
      way of doing things has blinded us to the fact that it is more fundamentally a
      way of thinking, knowing and valuing.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7801153
TI  - The forms and limits of medical ethics.
AB  - As medical ethics has evolved over the past several decades, it has come to be
      regarded as a domain of applied ethics, that is, the application of a rationally
      based, philosophical theory to moral problems in health care. But an array of
      difficulties arise in the attempt to apply general moral theories or norms to
      concrete problems, difficulties that expose the incompleteness and indeterminacy
      of philosophical moral theory. The doubtful ability of applied ethics to be
      practically helpful has led to the development of two main competitors. One is
      the attempt to reprise and rehabilitate the tradition of moral casuistry, which
      focuses on the analysis of specific cases rather than on the defense and
      application of theories and norms. The second is the search for moral insight and
      guidance in narratives or stories. These alternatives suffer from some of the
      same difficulties that plague applied ethics, however. Another trend in medical
      ethics rejects the theoretical preoccupation of applied ethics in favour of
      contextualism--an insistence on situating moral problems in institutional and
      organizational structures and in social and cultural backgrounds. Social science
      investigations of medical ethics pay attention to the former, while feminist
      critiques of medical ethics are concerned with exposing and eradicating cultural
      biases against women. Contemporary work in medical ethics is diverse, but these
      manifold approaches hold out the promise of improving our understanding of
      morality as a truly practical enterprise.

PMID- 7801154
TI  - Violence against women: a neglected public health issue in less developed
      countries.
AB  - Violence against women is a significant public health issue in countries of both
      the industrialized and less developed world. This paper describes the magnitude
      and health consequences of domestic violence and rape, with an emphasis on
      developing countries; it recognizes, however, that there is a dearth of
      documentation regarding the wide range of activity opposing violence against
      women which is taking place in less developed countries. It briefly explores the
      factors that perpetuate violence against women and the strategies that have
      evolved to respond to the problem. It analyses the constellation of factors that
      may assist violence to emerge as a legitimate public health concern, and explores
      opportunities and obstacles to further progress in this field. Particular
      attention is devoted to the role of research in the policy-making process;
      research areas which may assist those opposing violence against women in all its
      forms are tentatively suggested.

PMID- 7801155
TI  - Domestic violence--an emerging health issue.
AB  - The aim of this paper is to explain some of the aspects included in the concept
      of family violence, to summarize the principal theoretical models proposed to
      explain it, as well as to describe the principal syndromes included within the
      scope of the concept: battered woman, courtship violence, child-abuse, child
      sexual-abuse, child witnessing violence, sibling violence and elderly violence.
      Particular emphasis is put on the description of the effects that different types
      of family violence cause on the individuals' health.

PMID- 7801156
TI  - Efficiency and equity implications of the health care reforms.
AB  - The purpose of the paper is to reflect on the recent health care reforms in both
      developed and developing countries, in the light of the evidence that has
      accumulated over the last few years about the efficiency and equity of different
      fiscal and organisational arrangements. The scene is set by a brief review of the
      definitions of efficiency and equity and of the confusions that often arise; and
      of the problems of making assessments in practice with real data. The evidence
      about effectiveness, efficiency and equity at the macro level are reviewed: among
      OECD countries, there is little evidence that variations in the levels and
      composition of health service expenditure actually affect levels of health;
      equity in financing and delivery appears to mirror equity in other sectors in the
      same countries; about the only solid--although rather limp--conclusion which is
      transferable is that costs can be contained best via global budgeting. The range
      of reforms in the North is sketched: despite calls to give people 'freedom' to
      opt out, public finances continues to be preferred among OECD countries; and the
      evidence that health care markets can actually function is 'weak'. Whilst
      geographical redistribution of finance has proved to be possible, inequalities in
      health remain in most countries. But the overwhelming impression is that the
      quality of the data base for many of these studies is appalling, and the
      analytice techniques used are simplistic. The move to introduce user charges in
      the South is discussed. It seems unlikely that they will raise a significant
      fraction of overall revenue; exemptions intended for the poor do not always work;
      and other trends are likely to exacerbate the patchy coverage of health care
      systems in the South. The final section reflects on the pressures for increased
      accountability. The emphasis on consumerism in the North has led to an increasing
      number of poorly designed 'patient satisfaction' surveys; in the South, there has
      been an increasing rhetoric on community participation, but little sign of actual
      devolution of control. The flavour of the decade is 'outcome measurement' which
      has been promoted feverish but with little rigour. We must also be concerned that
      this emphasis will, once again, be hijacked by the most articulate.

PMID- 7801157
TI  - Equity and efficiency in health reform. A European view.
AB  - Health care reform in both eastern and western Europe is on the agenda, and in
      both parts of Europe the importance of equity targets has been questioned. In the
      East, the previously strongly held equity goals were largely a facade, covering
      all sorts of privilege systems, something which has brought equity as a concept
      into disrepute. However, present developments mean that it is quite likely to be
      back on the agenda again soon. In the West, equity has been seen as inevitably
      linked to non-market systems of health care. In moving towards market solutions
      equity has come to be seen as conflicting with efficiency goals. This contra
      positioning of equity and efficiency does not stand up to critical examination.
      It is based on confusing strategic goals with the implementation of those goals.
      Equity could be seen as a strategic goal in its own right. We may ask what are
      the most efficient ways of financing, managing and delivering medical services to
      achieve that goal. Clearly this has not been the question on the agenda. Cost
      containment has been imperative, and the consequences for general health, equity
      in health or the health and care for those suffering most, has been relegated to
      second place. The reduction of inequalities in health can be seen as an overall
      strategy for the improvement of a population's health, and as helpful in the
      maintaining and improvement of its human capital.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7801158
TI  - The sociology of entrenchment: a cystic fibrosis test for everyone?
AB  - In this article we introduce the notion of entrenchment to conceptualize the
      processes in which new technological options, through the interactions between a
      variety of actors, become viable and established practices in society, both
      satisfying and modifying needs and interests. The notion of entrenchment we use
      as a framework for an analysis of developments and debates in the field of cystic
      fibrosis testing and screening in Denmark. On the one hand, it appears that the
      development and introduction of cystic fibrosis (CF) screening to some extent is
      predetermined both by existing networks of human genome researchers, clinical
      geneticists, patients (organizations), funding organizations, and regulatory
      agencies, and by existing practices like that of prenatal diagnosis. On the other
      hand, in Denmark, the content and future of CF screening is shaped in ongoing
      processes or articulation of demand for screening and of its cultural and
      political acceptability, processes which also involve political decision-making
      and which (may) result in new networks and regimes. Yet, what appears to be an
      inherent and undecided part of the process of entrenchment of CF screening in
      Denmark, is how to allocate responsibilities and authority to decide what is
      acceptable and what not.

PMID- 7801159
TI  - Mapping the human genome--friend or foe?
AB  - The Human Genome Project represents one of science's most significant advances.
      It offers to individuals and communities the capacity to make informed and
      autonomous decisions. However, it also poses fundamental questions which, it is
      argued, should be in contemplation now. If mechanisms for the resolution of these
      issues are not in place before the conclusion of the project, and are not
      available to guide and control its progress, individual privacy may be seriously
      affected. Employers, insurers and many other groups may seek access to
      information which would otherwise be confidential to the individual; families may
      be torn apart by the information held by one member in respect of the collective
      gene pool of the family unit. The law has a key role to play in encouraging the
      sensible use of this information, whilst at the same time protecting individuals
      and their rights.

PMID- 7801160
TI  - Ethnological studies of medical sciences.
AB  - A broad overview of ethnological (anthropological) methods and theory is
      presented historically and conceptually. Medical sciences are assumed to be
      socially produced and reproduced, and a cross-cultural perspectives helps us view
      them more objectively. Discussion is organized in a framework of general systems
      theory, and illustrated primarily from recent literature on childbirth. Linkages
      and communication between different levels of systems: patient, profession,
      society and ecology, focus on interaction between levels, much of which is
      ritualized and political.

PMID- 7801161
TI  - Gender inequalities of health in the Third World.
AB  - This paper examines gender inequalities of health in Third World Countries.
      Health hazards are present at every stage of a woman's life cycle. Health
      problems which pose the greatest hardship to women in these countries include:
      reproductive health problems, excess female mortality in childhood, violence
      against girls and women, occupational and environmental hazards, and cervical and
      breast cancer. Many of these lead to maternal mortality which was the most
      focussed upon indicator of women's health in the literature. Gender inequalities
      of health originate in the traditional society where definitions of health status
      and traditional medical practices all reflect the subordinate social status of
      women. Gender inequalities in health are manifested in traditional medical
      practices which attribute women's illnesses to behavioral lapses by women;
      differential access to and utilization of modern healthcare services by women and
      girls, including maternal care, general healthcare, family planning and safe
      abortion services. Reasons for gender inequalities in health include--emphasis on
      women's childbearing roles resulting in early and excessive childbearing; sex
      preference manifested in discrimination against female children in health and
      general care; women's workloads which not only expose them to health hazards but
      also make it difficult for them to take time off for healthcare; lack of autonomy
      by women leading to lack of decision-making power and access to independent
      income; early marriage which exposes women to the complications of early and
      excessive childbearing. Gender inequality in health is one of the social
      dimensions in which gender inequality is manifested in Third World societies.
      Strategies to eradicate gender inequalities in health must therefore involve
      efforts to improve the status of women.

PMID- 7801162
TI  - Gender inequalities in health in the Third World: uncharted ground.
AB  - Gender differences in health in developing countries have, until recently,
      received little attention from researchers, health programmes and international
      development efforts. This paper highlights several issues related to gender and
      health in the Third World on which information, especially of an empirical
      nature, is inadequate. These include certain health conditions and diseases for
      which gender differences remain largely uncharted, gender inequalities in the
      development of health and contraceptive technology, the lack of gender
      sensitivity in the provision of health services, and gender inequalities in
      health policies, focusing mainly on structural adjustment. Questions urgently
      requiring research are identified and suggestions are made for improving the
      gender sensitivity of health policies and interventions.

PMID- 7801163
TI  - Health and human rights: the challenge for developing countries.
AB  - What are the priorities when it comes to health and human rights? This article is
      subtended by the following principle, i.e. issues of health and human rights must
      be considered from different angles in industrial countries and developing
      countries. Indeed, the subjects that preoccupy the countries of 'the North,' such
      as the ethics of mandatory screening, assisted insemination, and euthanasia, to
      name a few, are of only marginal importance in the 'South.' The exception is the
      very specific case of health services' involvement in the organization of
      torture, which is common to North and South. Geographical, economic and cultural
      barriers have been lowered or removed in most industrialized countries and using
      effective, good-quality services has become a right for the overwhelming majority
      of their citizens. Priority in the developing countries continues to be given
      above all to improving the quality and effectiveness of health services and
      making them accessible to the greatest number of people. This article starts with
      a brief historical overview of the development of the 'health and human rights'
      concept. The body of the paper will then be devoted to an analysis of constraints
      and identification of the solutions that will allow health to become a real
      'human right' for the people of developing countries. Health as a human right is
      the challenge for developing countries.

PMID- 7801164
TI  - Drugs, sex and social science: social science research and health policy in
      Australia.
AB  - Social science health research in Australia has undergone considerable expansion
      through government sponsorship of projects that complement or address issues
      related directly to policy and program concerns. In examining the rationale for
      supporting social science research, and the difficulties that social scientists
      often face in return in presenting their work in ways that might optimize
      funding, the paper first explores the paradigmatic tensions between social and
      biomedical scientists, that in turn influence funding decisions and potentially
      the receipt and uptake of social research. It also addresses the incorporation of
      the language and concepts of social science within policy documents, using
      'ethnicity' as an exemplar of this. The paper then documents and analyses federal
      targeted-funding programs for health research, and the measures taken to
      encourage policy-relevant research. In particular, the paper discusses the
      funding programs that operate for drug and alcohol use and HIV/AIDS.

PMID- 7801165
TI  - The impact of social science research on health policy.
AB  - The relationship between research and health policy is discussed from a policy
      process perspective, describing communication problems in the course of policy
      formulation, implementation and evaluation. Policy process is often expected by
      researchers to be rational, having logical sequence of steps and the objective
      evaluation of alternatives based on scientific knowledge. In fact, policies are
      often formulated without clear problem identification or based on wrong
      assumption. The timing of research and policy-making differs. Policy-makers need
      to respond quickly. Evaluations may be regarded by politicians as embarrassing if
      they point to a need for significant change. It is not satisfactory to consider
      only research and policy-making: their relationship is influenced by the media,
      different interest groups and by the general public. Health policy formulation is
      embedded in the general policy environment of particular societies. Some
      countries have a long tradition of consensus-building, while in others health
      reforms have been formulated and introduced in a centralized way. Traditional bio
      medical thinking influences health policy-makers. The importance of social and
      political acceptability tends to be overlooked. The paper emphasizes that we are
      experiencing an era of scarcity of resources and growing tension concerning
      allocation decisions. Existing institutions provide insufficient incentives for
      policy-makers and researchers to promote public dialogue about such issues. The
      paper concludes that there is a need for new approaches to policy development and
      implementation, new structures in policy-making, changes in research financing
      and co-operation between disciplines and new structures for public participation
      in policy-making. Research should facilitate more open and democratic dialogue
      about policy options and the consequences of alternative choices.

PMID- 7801166
TI  - Policy implications of differential health status in East and West Europe. The
      case of Hungary.
AB  - Morbidity and mortality trends in Western and Eastern Europe have differed
      considerably during the past three decades, although the major unfavourable
      processes have been essentially the same in each of the Central European
      countries. The most striking feature has been the decline in average life
      expectancy and deterioration of age-specific mortality rates for the middle-aged,
      especially men. The former socialist government took no effective action. Due to
      the denial of social and environmental problems, social, health and environmental
      policy were underdeveloped and deformed. Partly inherited from previous
      historical traditions, wishful thinking, victimization and a patronizing attitude
      were primary ways of dealing with problems. In these circumstances even the few
      specially supported health education campaigns were doomed to fail. People
      depended on the omnipotent central state in vain to solve their problems so that
      health promotion based on the community and self-empowerment did not develop.
      During the early nineties, in Eastern and Central Europe no central political
      strategies were initiated or launched to combat the mortality and morbidity
      tendences. The economic and social prerequisites of a long-term gradual
      improvement in the health status are missing in Central and Eastern Europe. A
      declining standard of living due to recession, growing deprivation, poverty,
      unemployment and migration are unfavourable to improvements in health. In a time
      of crisis, with stress but without adequate skills of coping, forced adaptation
      associated with sudden changes and perceived failure have only made matters
      worse. There are no short-term 'solutions'.

PMID- 7801167
TI  - From population control to reproductive health: an emerging policy agenda.
AB  - This article reviews the background to the current debates between advocates of
      population control and reproductive health as frameworks for national and
      international health policies. Population control has been a dominant metaphor in
      international family planning programs since the 1960s. Population control has
      frequently meant pursuing a single-minded goal of fertility limitation, often
      without sufficient attention to the rights of family planning clients. This
      narrow focus has led to some coercive policies, numerous ethical violations, and
      ineffective family planning programs. In the last decade there has been the
      beginning of a policy shift, advocated by a growing number of activists and
      researchers in women's health, from population control to reproductive health. A
      reproductive health framework would provide a broader programmatic focus that
      could bring needed attention to such issues as sexually transmitted diseases,
      infertility, abortion, reproductive cancers and women's empowerment generally.

PMID- 7801168
TI  - The role of the state in health systems.
AB  - The object of this paper is to update the debate concerning the State's role in
      health systems services regarding the experience of the last decade. It is argued
      that it is impossible to give an account of the problem's complexity without
      bearing in mind the social science contribution concerning the crisis in Welfare
      States.

PMID- 7801170
TI  - Stigmatization, scapegoating and discrimination in sexually transmitted diseases:
      overcoming 'them' and 'us'.
AB  - It is recognized that AIDS involves multiple epidemics. As well as an epidemic of
      HIV, we are experiencing epidemics of fear and of stigmatization, scapegoating
      and discrimination associated with AIDS. In this paper, we investigate the nature
      of these reactions and the links between them. In doing so, we identify some of
      their causes. We likewise investigate counter-reactions, pre-eminent among which
      is the promotion of concepts of respect for persons and for human rights. We also
      examine the 'tools' used to elicit and manifest both these reactions and counter
      reactions. In all cases, these 'tools' include choice of language--especially in
      the form of metaphor and rhetoric--and the use of symbolism. We conclude that in
      order to deal humanely and compassionately with AIDS and persons with AIDS, and,
      ultimately, to protect society (including, the fundamental principles and rules
      on which it is based), a primary requirement is to recognize that we are all
      living with AIDS, whether infected or affected by it; that is, in the context of
      AIDS, it is imperative that we overcome any divisions into 'them' and 'us'.

PMID- 7801169
TI  - The social impact of aging populations: some major issues.
AB  - Demographic trends regarding the issue of aging underscore the fact that both
      current situations and future trends directly concerns all of us. Aging is the
      reality for the future world. The pace at which demographic transition develops
      varies among countries and regions of the world, but most of the developed and
      developing countries will be challenged by increasing numbers of dependent
      individuals. This is particularly critical in the less-developed countries where
      older populations will increase substantially faster. It is expected that by the
      year 2000, Latin America and the Caribbean will have 41 million elderly, 7.2% of
      the total population. By 2025 this percentage will increase to 10.8%. The
      stunning growth of the elderly demands special attention of policy and decision
      makers. The total dependency ratio will decrease in the Americas between 1980 and
      2025 due to a marked decrease in the fertility rate, whereas old age dependency
      ratios will show a marked increase in all countries except Haiti and Surinam.
      Most of the elderly populations, predominantly women, are living in urban
      centers. This fact is one of the most important characteristic of the
      socioeconomic picture in Latin American and Caribbean countries: urbanization
      with poverty. Women are bearing mainly the burden. It is obvious that, from a
      cultural perspective, the social impact of aging populations is a complex issue.
      The wide range of possible future programs will be the result of differences and
      similarities in social values, relationships, and dynamics within each society.
      It is important to recognize that since modern industrialized societies live in a
      culture emphasizing competition for economic wealth, that values economic over
      social productivity, and where inequities based on class, gender, and race are
      accepted, that these are the issues influencing the parameters of aging
      populations. Social policy development for the elderly needs to be critically
      examined in order for society to adapt to aging as well as for older populations
      to adapt to a charging society. The major political challenge is the need for
      redistributive policies. Developing countries must add new priorities to their
      scarce resources, for social programs for elderly, while still having to deal
      with the problems of their younger populations. Women issues are extremely
      important in considering social policies for elderly population. Feminization of
      poverty and ill-health during old age is a result of exacerbated risks for women
      across the life course. Appropriate care and support for this vulnerable group is
      a priority.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7801171
TI  - Stigmatization and AIDS: critical issues in public health.
AB  - From Goffman's classic sociological work on stigma to Sontag's popular works on
      metaphors, stigma has captured academic and general public interest. The severity
      of the AIDS pandemic has transformed our lives profoundly, and the stigma
      experienced by persons with AIDS has grave consequences for public health
      efforts. Fears of the consequences of open discourse and self-identification have
      created a silence that threatens all of us. Using analyses of Western imagery and
      African ethnographic accounts, this paper explores the differences between AIDS
      in America and in Africa with respect to epidemiology, socio-economic and
      cultural illness patterns, and experiences of stigmatization. Several research
      questions are posed to stimulate discussion of future ethnographic work on
      illness and stigma in Africa. The paper concludes with a discussion of the impact
      on public health of four types of AIDS stigmatization: theologically-based blame,
      liberal concern for the health of those not afflicted, risk group problem and
      civil rights problem. From the point of view of enlightened management of public
      health, the civil rights issue poses the most serious threat. The tension between
      the rights of the individual, who is at risk of exposure and condemnation because
      of stigma, and the rights of the rest of society, interferes with the development
      of large-scale, effective public health programs.

PMID- 7801172
TI  - Social science education as a component of medical training.
AB  - The broad view of health espoused by the World Health Organization is now
      generally accepted by medical educators. Implicit in the new paradigm is a
      recognition of multiple determinants of health and of shifting divisions of
      professional responsibilities among providers. As a consequence, the importance
      of social and behavioural science education as a foundation to medical training
      is increasingly appreciated. At the same time medical programmes are under
      pressure to contend with the explosion of knowledge in basic biomedical and life
      sciences and with technological innovation. Curricula are being submerged in
      facts, causing medical schools to look for innovative teaching models that
      feature more flexible approaches to the diverse body of knowledge supporting
      professional practice. Independent learning methods are being explored and
      revised teaching programs are being organized around coordinating themes, such as
      aging, human development and environmental health. Future programmes must be
      designed to encourage multiprofessional approaches while fostering awareness of
      the important interplay between health care (both curative and preventive) and
      social/behavioural science. Within the curriculum students should be offered
      options that include sociology, child growth and development, gerontology,
      medical anthropology, psychology, medical geography, health economics, political
      science and related subthemes. More important than the inclusion of any specific
      discipline is the creation of an environment in which future physicians may be
      exposed to critical thinking across a wide range of themes that characterize the
      social and cultural context for medical practice. Such enquiry is also likely to
      drive a closer relationship between medical schools and their parent universities
      within which the social science expertize resides.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7801173
TI  - Health delivery standards: vested interests in health planning.
AB  - The thread of this paper is that vested interests prevail consistently in the
      formulation of health policy and provision of health services. Several African
      countries illustrate how the health care standard becomes an end in itself,
      however ineffective it becomes as population and needs change. Policy is not an
      exclusive prerogative of governments. Industry of all sorts, non-governmental
      organizations (NGOs) and development agencies use policies to determine, guide
      and shape investments and, in the case of the private sector, prevail favourably
      in competition. With a few exceptions, planners plan to depict and alter a
      particular situation, to improve conditions according to a particular mode,
      ideology or belief. The planner, like the policy maker, assumes that certain
      changes will occur if certain decisions are made or actions are taken. In
      reality, however, policy makers and planners are seldom satisfied with the status
      quo. The policy maker decides on the basis of available information, albeit
      incomplete or inconclusive, and believes one option is better than another or
      that it will achieve the desired goal optimally and at least cost. To formulate
      policy is to choose a course of action and to plan is to pursue a particular
      interest. However implicitly, vested interests are entrenched in every policy
      action. There seems to be four main, but related reasons for any specific health
      policy: availability of adequate health care; equity of access; cost; and
      effectiveness/relevance of the system under the prevailing technology. While
      concerns differ, sometimes quite widely, concern for an effective health system
      is always paramount. Less than two decades ago, African countries had more robust
      economies than they have today.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7801174
TI  - Planning in the health sector: for whom, by whom?
AB  - To state that there are vested interests in health planning is to state the
      obvious. One can identify numerous actors ranging from international agencies,
      government officials, pharmaceutical companies, health personnel and community
      and citizen's groups which would like to stake a claim on the direction and
      nature of planning and implementing health policy. We argue that the role of
      specific actors can only be seen in the broader social, economic and ideological
      framework which, consequently, determines the working of the model of health
      care. Probably the most important factor influencing health planning is the
      influence of international donors, governments and agencies. The present
      ideological tilt towards the market, privatization, less government and more
      liberalization, has had important repercussions on health planning and delivery.
      Furthermore, the debt crisis, and the stabilization and structural adjustment
      programmes being followed by a very large number of underdeveloped countries, are
      transforming health systems. Essentially, vested interests in health planning
      within countries, need to be seen in the light of recent ideological and economic
      changes, and international relations of aid, power and domination.

PMID- 7801176
TI  - Health outcomes related to low back pain.

PMID- 7801175
TI  - What is needed to claim adequacy in health services?
AB  - The answer to the question in the title of this essay is fairly readily available
      and can be articulated by listing those attributes that spell out adequacy in
      health services. A series of other concepts are presented to highlight methods of
      analysis in judging adequacy. These fall into two categories, those value
      statement that give meaning to the question to begin with as well as to its
      answers; and those of more mechanical significance. The first appear in the form
      of general principles, having to do with means, ends and the maintenance of human
      life; the worth of human life and common ownership of resources; and overriding
      contradictions with health-oriented life. The second--mechanics and techniques in
      judging the presence or lack of health services--are addressed by the concepts of
      conditionality and prioritization. Examples are provided from the current health
      planning efforts in the United States as viewed by a professional organization,
      by the Clinton administration's proposal for adequate health care, and finally,
      those offered by the Republican party.

PMID- 7801177
TI  - Clinical outcomes. Spine focus issue.

PMID- 7801178
TI  - A brief introduction to the critical reading of the clinical literature.
AB  - Clinicians are bombarded by reports of new diagnostic tests or treatments for
      patients with spine problems. To provide the best possible patient care,
      clinicians need to be able to critically appraise the results of such studies for
      validity and relevance to patient care. Important questions to be asked of any
      description of diagnostic or treatment studies are the following questions: 1)
      Are the patients described in detail so that you can decide whether they are
      comparable to those that you see in your practice? 2) Are the treatments or
      assessments described well enough so that you could provide the same for your
      patients? 3) Was a clinically relevant endpoint measured? 4) Is there an
      appropriate comparison group? 5) Are potential sources of bias appropriately
      attended to? 6) Are the results clinically significant?

PMID- 7801179
TI  - Outcome measures for studying patients with low back pain.
AB  - There is growing recognition in the treatment of back pain that patient
      perspectives are essential in judging the results of treatment. Improving the
      patient's "quality of life" is often the main goal of therapy. Thus, although
      clinical research in the past has focused on physiologic outcomes, such as range
      of motion, muscle strength, or neurologic deficits, increasing attention is being
      given to the rigorous measurement of symptoms, functional status, role function,
      satisfaction with treatment, and health care costs. In many cases, these so
      called "soft" outcomes can be measured with a level of reproducibility similar to
      more conventional clinical data such as imaging test results. Because symptoms
      and functional outcomes are sometimes only loosely associated with physiologic
      phenomena, the former outcomes should be measured directly. Modern questionnaires
      for measuring patient quality of life combine the expertise of social scientists
      and clinicians and have demonstrated validity. Furthermore, they have some
      important advantages over simple ratings of "excellent, good, fair, and poor"
      outcomes, or work status alone. Several modern instruments for measuring health
      related quality of life in patients with low back pain are reviewed briefly,
      describing their content and length. Wider use of these instruments would help to
      increase clinician familiarity with their meaning and avoid duplication of effort
      in questionnaire development.

PMID- 7801180
TI  - Strategies for outcome research in spinal disorders. An introduction.
AB  - The evaluation of the clinical utility of the clinical diagnostic tests and
      procedures, what works in spinal disorders, and for whom and how treatment
      affects a patient's symptoms and function are key questions of outcomes research.
      This paper describes the advantages and limitations of the main study approaches
      used. Examples from the spine literature on spinal stenosis are used for
      illustration.

PMID- 7801181
TI  - Studying the natural history of back pain.
AB  - Improved information on the natural history of back pain is needed to enable
      doctors and their patients to understand the likely course of back pain and to
      evaluate whether alternative interventions are preferred over self care or
      watchful waiting. The course of back pain is highly variable, occurring in
      transient, recurrent, and chronic phases. Recent longitudinal studies suggest
      that back pain is typically a recurrent condition and that chronic phases of back
      pain occur more often than previously believed. New methods of studying the
      course of back pain, standardized definitions of phases in the natural history of
      back pain, and improved outcomes data are needed to better understand the short
      term and long-term course of back pain.

PMID- 7801182
TI  - A guide to interpreting epidemiologic studies on the etiology of back pain.
AB  - Understanding disease etiology is key for effective preventive or therapeutic
      interventions. Knowledge about risk factors is useful to the clinician to answer
      patients' questions about the possible cause(s) of their presenting disorders.
      This article describes the three most common types of etiologic studies using
      examples from the published literature on the risk factors for back pain. Cohort
      studies typically follow a group of "healthy" people forward in time to assess
      disease outcome after risk factors have already been measured. Case-control
      studies use people selected on the basis of outcome status; risk factors are
      assessed after the fact. Although more prone to bias than cohort studies, case
      control studies are more common in back pain research because of the ease of
      examining several risk factors simultaneously and the expense of cohort studies.
      Prevalence studies use a random sample of people collected at a single point in
      time; consequently there is no predetermined number of "cases" and "controls,"
      their numbers depending on the prevalence of disease and exposures in the
      samples. To assist in the interpretation of research findings this paper presents
      a general framework for assessing the strengths and weaknesses of an individual
      study. Case-control studies are discussed in more detail because they are so
      commonly encountered in the etiologic literature. Finally, because the evidence
      from a single study, no matter how well designed and executed, is never enough on
      its own to decide if a risk factor is causal or not, the paper concludes by
      briefly summarizing the criteria for inferring causation using the full body of
      available biologic and epidemiologic literature.

PMID- 7801183
TI  - Designing studies of diagnostic tests for low back pain or radiculopathy.
AB  - New diagnostic tests for the evaluation of patients with low back pain are
      constantly emerging, but are often not completely evaluated before they become
      used. Many published studies have a number of biases that tend to exaggerate the
      estimated accuracy of a diagnostic test. Several key study design features should
      be considered in such studies: independent comparison of the diagnostic test
      results with an appropriate "gold standard"; blinded assessment of the new test
      and the gold standard or competing tests; the reproducibility of interpretation
      of the test being examined; and the sensitivity and specificity of the test for
      the final gold standard diagnosis. In addition, evaluations of test accuracy
      should include patients with a wide spectrum of illness from mild to severe, and
      the study setting and patient characteristics should be described in detail.
      Finally, the contribution of a diagnostic test to the overall validity of a full
      group or sequence of tests should be considered, and, ideally, the effect of the
      test on actual patient outcomes should be determined.

PMID- 7801184
TI  - An introduction to therapeutic trials for low back pain.

PMID- 7801185
TI  - Therapeutic trials for low back pain.
AB  - Little consensus exists regarding the indications for and effectiveness of many
      back pain treatments. This clinical uncertainty arises because most back pain
      research has been flawed by poor methodology. The authors discuss strategies for
      improving the quality of back pain research on treatment efficacy. Design
      features, including randomized treatment allocation, independent outcome
      assessors, comprehensive outcome measures, appropriate statistical analyses, and
      close patient follow-up can increase study validity. Complete descriptions of
      enrollment criteria, patient characteristics, and clinical interventions can
      increase the generalizability of results. Although large scale trials often
      involve university centers, community-based researchers can collaborate on
      randomized trials or conduct valuable cohort studies.

PMID- 7801186
TI  - Meta-analysis. A useful tool for the spine researcher.
AB  - Meta-analysis is a systematic and objective methodology for synthesizing research
      literature. The authors present the history and definition of meta-analysis,
      discuss the generic framework for design and implementation of a meta-analysis,
      and review the problems and pitfalls that can accompany meta-analyses. Their
      discussion draws on practical experience with several meta-analyses of the low
      back pain literature. Meta-analysis can be used to help answer the questions
      about various options for diagnosis and treatment of low back problems and also
      to point out gaps in our knowledge base that may have a high priority for
      research. Meta-analytic methods are an informative means of addressing health
      care controversies with major patient management and cost implications.

PMID- 7801187
TI  - Analysis of automated administrative and survey databases to study patterns and
      outcomes of care.
AB  - Large computerized databases often arise from national surveys, insurance claims,
      and statewide health care registries. These databases are increasingly used to
      examine patterns of medical care and certain outcomes of care and may be helpful
      in planning clinical trials. They are highly representative of defined
      populations, but have limited clinical information. Methods have been developed
      to identify episodes of low back pain and to quantify the severity of unrelated,
      comorbid medical conditions. Pitfalls in analysis are discussed, including
      limitations of diagnosis and procedure coding, cross-sectional nature of most
      data, limited clinical detail, and the necessarily observational (not
      experimental) nature of any group comparisons. There is growing interest in
      expanding the clinical information in such databases, for both quality
      improvement and research purposes.

PMID- 7801188
TI  - Why does geographic variation in health care practices matter? (And seven
      questions to ask in evaluating studies on geographic variation).
AB  - One of the most active fields in health services research is the study of
      "geographic variation," or disparities in rates of certain types of health care
      practices among large areas (such as countries or regions of a country) or small
      areas (such as countries or hospital market areas); "small area analysis" in
      particular has received much attention in journals and the popular press.
      Increasingly, data upon which to base studies of geographic variation are
      becoming available. This article poses questions to ask in applying studies on
      geographic variation to health care settings. Because findings from these studies
      may ultimately affect patient care, the questions are important for physicians as
      well as health services researchers. The questions are: 1) What events are to be
      analyzed? 2) What geographic units are to be analyzed? 3) How good are the data?
      4) Are differences in rates due to chance alone? 5) Are high rates too high? 6)
      How is geographic variation to be explained? 7) What is the role of "presentation
      style" in explaining geographic variation?

PMID- 7801189
TI  - Economic decision analysis in the diagnosis and treatment of low back pain. A
      methodologic primer.
AB  - This article outlines basic principles for the economic analysis of clinical
      decisions. Using a hypothetical scenario involving a patient with low back pain,
      the specific application of cost-benefit analysis (CBA) and cost-effectiveness
      analysis (CEA) is illustrated; and the two methodologies are compared. Cost
      benefit analysis is advanced in the "gold standard" among the two approaches
      because it forces decision makers to explicitly value both the cost and health
      consequences of alternative clinical actions.

PMID- 7801190
TI  - [The possible significance of beneficial radiation effects in cells for the whole
      organism].

PMID- 7801191
TI  - [Reduction of radiation exposure with digital luminescence radiography
      exemplified by roentgen diagnosis of the pediatric pelvis].

PMID- 7801192
TI  - [3-D reconstruction of CT images with a peripheral peripheral 3-D image
      processing computer--initial experiences].

PMID- 7801193
TI  - [Aneurysm of the hepatic artery with liver infarction: diagnostic value of
      imaging procedures].

PMID- 7801194
TI  - [Spiral CT versus standard CT of the orbits--case report].

PMID- 7801195
TI  - [Now is the time to establish in rheumatoid surgery].

PMID- 7801196
TI  - [Nitroglycerin tape for Raynaud's phenomenon of rheumatic disease patients--an
      evaluation of skin temperature by thermography].
AB  - Topical nitroglycerin has been tried for the alleviation of Raynaud's phenomenon
      in rheumatic diseases, but its effect is not widely recognized. We evaluated the
      effect of nitroglycerin tape (NTG tape) for peripheral circulatory failure of 7
      patients with rheumatic diseases (4 women and 3 men, aged 35-73 years). The
      underlying rheumatic diseases included: systemic sclerosis 4 patients,
      polyarteritis nodosa (PN) 1 patient, cutaneous PN 1 patient and digital
      microinfarction with pulmonary fibrosis 1 patient. An NTG tape (containing 2.5 mg
      of nitroglycerin) was applied unilaterally on one forearm or leg, and the change
      in skin temperature was evaluated by thermography. Skin temperature of the
      extremities significantly increased at 2 and 3 hours after the application of NTG
      tape. Feeling of cold and/or pain improved in all patients. Adverse effect was
      headache in one patient. These results suggest that NTG tape may deserve further
      use in the treatment of peripheral circulatory failure in patients with rheumatic
      diseases.

PMID- 7801198
TI  - [The clinical manifestations of Sjogren's syndrome in children].
AB  - Sjogren's syndrome (SS) is thought to be uncommon in children. We studied the
      clinical manifestations and laboratory findings of 12 pediatric patients with SS,
      all of children did not have sicca symptoms but have lymphocytic infiltration of
      salivary glands, abnormal sialograms or abnormal results of scintigraphy
      compatible with typical SS. Seven cases had primary SS and five were secondary SS
      and had other autoimmune disorders (three cases with systemic lupus
      erythematosus, one case with dermatomyositis, and the other with mixed connective
      tissue disease). All patients were female. The mean age at onset of symptoms,
      including other autoimmune manifestations, was 12.2 years (range 9-15 years). The
      initial symptoms were some systemic manifestations (fever, exanthema, arthralgia,
      etc.) and various autoimmune phenomena (butterfly rash, Raynaud's phenomenon,
      proteinuria, weakness of muscles, etc.). On the other hand, no patients
      complained sicca symptoms. Laboratory studies in our patients revealed elevated
      levels of IgG (92%), antinuclear antibody (92%), rheumatoid factor (58%), anti-SS
      A antibody (75%). These findings were similar to those found in adult patients
      with sicca symptoms previously reported in literature. From these studies, we
      suggest that lip biopsy, sialography and/or salivary gland's scintigraphy should
      be carried out in patients who had abnormal laboratory findings as mentioned
      above, irrespective of absence of sicca symptoms, in order to diagnose SS at
      early period.

PMID- 7801197
TI  - [Expression of adhesion molecules, intercellular molecule (ICAM)-1 and lymphocyte
      function associated antigen (LFA)-1 in the synovial tissues of rheumatoid
      arthritis (RA)].
AB  - We histochemically examined the expression of adhesion molecules, ICAM-1 and LFA
      1, of endothelial cells in the synovial tissues of rheumatoid arthritis. Subjects
      were 7 RA patients of 1, 3, 4 months and 2, 3, 5, 7 years duration, 2 cases of
      mixed connective tissue disease (MCTD), both of 5 years duration, and 3 cases of
      osteoarthritis (OA) 15 years after onset. ICAM-1 was expressed on the cell
      surface and in the cytoplasm of the endothelial cells of small veins, and in the
      germinal center of lymphoid follicle, while LFA-1 was expressed on lymphocytes
      around the small vessels which expressed the ICAM-1 molecule. The most
      characteristic point of this study was that we adopted not only histochemical but
      also quantitative methods. At one month from onset, faintly positive ICAM-1
      molecules were expressed on endothelial cells accompanied by LFA-1 positive
      spindle cells, called interstitial cells. Typical high endothelial venules (HEV)
      with intensive expression of ICAM-1 appeared 3 months after onset. These LFA-1
      positive lymphocytes consisted of equal numbers of CD4+ and CD8+ T lymphocytes.
      There were few B lymphocytes in the synovial tissues in the early stage. The
      number of small vessels expressing ICAM-1 decreased with the development of the
      lymphoid follicle, though the intensity of ICAM-1 expressed in each vessel was
      very high. Our data revealed that ICAM-1 was expressed not only in RA synovia but
      also in OA which is not ordinarily considered to be immunogenic inflammation,
      though the molecules were expressed on the flat endothelial cells and not HEV,
      without accumulation of lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7801199
TI  - [Detection of autoantibodies in sera from patients with rheumatoid arthritis].
AB  - Although Rheumatoid Arthritis (RA) is categorized in the systemic autoimmune
      diseases, specific autoantibodies in RA have been reported to be rare. We have
      investigated autoantibodies found in sera from patients with RA and examined
      their clinical significance. Immunoprecipitation techniques using 32P-labeled or
      35S-labeled HeLa cell extracts and immunoblotting were utilized to detect
      autoantibodies in sera from 42 patients with RA and 58 patients with other
      connective tissue diseases as controls. Certain autoantibodies were detected in
      33 of 42 patients (79%) with RA by any of the assay systems mentioned above. Anti
      SSA/Ro, anti-SSB/La, anti-7-2RNP, and anti-Sm antibodies were found in 13 (29%),
      3 (7%), 4 (10%), and 1 (2%) patients with RA, respectively. All 3 patients with
      anti-SSB/La and 9 with anti-SSA/Ro revealed Sjogren's syndrome besides RA.
      However, all 4 patients with anti-7-2RNP and one patient with anti-Sm showed no
      evidence of scleroderma nor SLE. Besides of these known autoantibodies, we have
      also detected 4 new antibodies which reacted with a 60kD protein in 15 (36%),
      45kD in 10 (24%), 75kD in 8 (19%), 180kD in 4 patients (10%) with RA. These
      autoantibodies were not found in other connective tissue diseases except one of
      SLE for anti-60kD and one of dermatomyositis for anti-75kD, and therefore
      appeared to be specific for RA patients. Anti-45kD antibodies were associated
      with low prevalence of anti-nuclear antibodies, and anti-180kD antibodies were
      associated with lymphadenopathy and Sjogren's syndrome. Thus, it was demonstrated
      that patients with RA develop a variety of autoantibodies as well as those with
      other connective tissue diseases.

PMID- 7801200
TI  - [A case of juvenile dermatomyositis with calcinosis universalis--remarkable
      improvement with aluminum hydroxide therapy].
AB  - Juvenile dermatomyositis (JDM) is a multisystem disease characterized by acute
      and chronic nonsuppurative inflammation of striated muscle and skin. JDM is
      classified into an independent entity in the classification of dermatomyositis,
      and it is marked by the development of calcinosis late in the course of the
      disease. Since an appropriate steroid therapy for the disease was established,
      the prognosis of the JDM has been improved except for a fulminant case. Frequency
      of calcinosis in JDM also has been decreasing because of the adequate steroid
      therapy. However, once calcinosis universalis occurs, this is the most
      troublesome and debilitating complication in JDM. Treatment of calcinosis
      universalis in JDM, so far, remains unsatisfactory. We report here a case of JDM,
      who suffered from at the age of 3 years, with calcinosis universalis that showed
      remarkable improvement to orally administrated aluminum hydroxide.

PMID- 7801201
TI  - [A case of systemic lupus erythematosus (SLE) successfully treated with
      mizoribine (Bredinin)].
AB  - Mizoribine, a novel immunosuppressive agent developed in Japan, was administered
      as a monotherapy to a systemic lupus erythematosus (SLE) patient with the
      clinical symptoms and immunological abnormalities accompanying SLE showing marked
      improvement. The result of prolonged administration over 22 months in this case
      showed neither relapse nor side-effects. Reports have been made about mizoribine
      used concomitantly with steroids in the treatment of SLE; however, there have not
      been any reports of mizoribine as a monotherapy for SLE being effective. In this
      case, mizoribine (150 mg/day) was administered without steroids as a monotherapy
      on a outpatient basis since the patient's condition overall was relatively good
      and the serious complications of the heart, kidneys, and lungs that accompany SLE
      were not observed. The results of this treatment showed improvements in alopecia,
      arthritis, and systemic malaise from about the 4th week after the start of
      administration, and the clinical symptoms that accompany SLE had completely
      disappeared in the 8th week. Also, the immunological tests markedly improved.
      Four months after the start of administration the immunological abnormalities in
      the anti-DNA antibody, rheumatoid factor, and immune complex were completely
      corrected. This case showed dramatic improvement in the SLE clinical symptoms and
      immunological abnormalities with the mizoribine monotherapy as well as the
      potential for mizoribine monotherapy to maintain a state of remission over the
      long term.

PMID- 7801202
TI  - [Primary biliary cirrhosis, rheumatoid arthritis and Sjogren's syndrome following
      implantation of ventriculoperitoneal shunt tube--an aged male case report].
AB  - A 73-year old male was received implantation of ventriculoperitoneal shunt tube
      (made with silicone) following subarachnoid hemorrhage in March 1991. Alkaline
      phosphatase was elevated gradually and he was diagnosed as having primary biliary
      cirrhosis by antimitochondria antibody and liver biopsy. He had been taking urso
      acid after that time on. He was admitted to our hospital because of stiffness and
      edema of both hands in November 1993. He was diagnosed as rheumatoid arthritis by
      morning stiffness with duration of few hours bilateral swelling of metacarpal,
      proxymal intrapharangeal and wrist joints and positive rheumatoid factor. In
      addition he felt dry mouth and laboratory data revealed that antinuclear antibody
      was 640x, centromere type, anti-SS-A antibody positive and elevation of
      circulating immune complex. A salivary gland disfunction was showed by gum test
      and salivary gland scintigraphy. Therefore the diagnosis of Sjogren's syndrome
      was made also. Connective tissue diseases have been reported to occur following
      cosmetic surgery with injection of the foreign substances paraffin and silicone.
      Now it is supposed to be the first case tcat connective tissue disease following
      ventriculoperitoneal shunt tube implantation.

PMID- 7801203
TI  - [Three cases of respiratory failure of collagen diseases accompanied by syndrome
      of inappropriate secretion of antidiuretic hormone (SIADH)].
AB  - We experienced three patients who have collagen diseases with respiratory failure
      accompanied by hyponatremia. They were one systemic lupus erythematosus patient
      with interstitial pneumonia, one rheumatoid arthritis patient with acute
      pneumonitis, and one dermatomyositis patient with pulmonary fibrosis and
      organizing pneumonia. In all 3 patients, hyponatremia appeared along with a
      decrease in arterial O2 partial pressure (PaO2) and the hyponatremia tended to
      improve when the PaO2 increased after inhalation of oxygen, even though their
      respiratory failure were not improved. In dermatomyositis patient, serum Na
      levels were over-corrected after increase in PaO2. The serum and urine
      osmolality, serum antidiuretic hormone (ADH) levels and clinical pictures
      demonstrated a presence of inappropriate secretion of ADH (SIADH) in all 3 cases
      when hyponatremia and hypoxia appeared. A close association between hyponatremia
      and hypoxia observed in 3 patients strongly suggested that their SIADH were
      associated with hypoxia since SIADH could be demonstrated by hypoxia. Therefore,
      it is important to realize that hypoxia-induced hyponatremia will be promptly
      corrected to hypernatremia by an oxygen inhalation, which could cause a lethal
      central pontine myelinolysis.

PMID- 7801204
TI  - [Clinical features of infantile patient with juvenile rheumatoid arthritis].
AB  - Little is known about clinical features of infantile juvenile rheumatoid
      arthritis (JRA) because it is very rare for the patients to develop JRA within
      one year of age. In the past 20 years, we experienced three JRA patients whose
      onset was under 1 year of age. The incidence of infantile JRA was 3.2% of all JRA
      patients in our facility. They are 9 month-old male with systemic onset, 6-month
      old female with polyarticular onset and 8 month-old female with systemic onset.
      It was difficult to evaluate subjective symptoms such as arthralgia or morning
      stiffness since the patients could not complain precisely. Therefore, careful
      observation on their behaviors, such as the delayed development of their motor
      function and bad humor and/or loss of activity in the morning, was important for
      evaluating joint symptoms. In case 1, measuring the serum level of hyaluronic
      acid was specifically useful to evaluate the arthritis. Drug therapy was not
      successful especially in infantile JRA. One of the reason for this
      ineffectiveness of drug therapy might be explained by poor adsorption of drugs in
      infants; the serum acetyl salicylic acid level was lower in infantile patients
      than the other patients with JRA even though they received enough dose of
      aspirin. Infantile JRA was revealed to have specific difficulties in early
      diagnosis and adequate treatment. Therefore, accumulated case studies about
      clinical features of infantile JRA is essential for their better prognosis.

PMID- 7801206
TI  - [Biomechanics of joint mechanical engineering laboratory].

PMID- 7801205
TI  - [Preliminary report of radical multiple synovectomy in rheumatoid arthritis].
AB  - We performed radical multiple synovectomy (RaMS) on rheumatoid arthritis (RA)
      patients who had multiple swollen joints in the mid or late course of RA. The
      objectives of this operation are to reduce the quantity of RA synovium as much as
      possible and to increase the efficacy of anti-rheumatic medication in order to
      achieve remission.2+ Nineteen RA patients who underwent RaMS were followed up for
      at least 15 months. In this series, anti-rheumatic medications were not changed
      after the operation, so that the effectiveness of the RaMS could be evaluated.
      The patients ranged in age from 44 to 73 years (mean: 55.8 years). The male to
      female ratio was 2:17. Duration after onset of RA ranged from 2 to 29 years
      (mean: 15.1 years). The swollen joint score according to Lansbury's evaluation of
      the RA activity index ranged from 7 to 24% (mean: 14.4%). The synovectomized
      joint score ranged from 7 to 22% (mean : 13.3%). The weight of the excised RA
      synovium ranged from 19.0 to 109.9 g (mean : 54.0 g). The number of operations
      was one in three patients, two in 15 patients and three in one patient. The
      postoperative results indicated that the modified Lansbury's index (morning
      stiffness, grip power, ESR, joint score), the values of ESR, CRP, Hb, TNF-alpha
      and IL-6 in the blood, and the peripheral lymphocyte CD4/CD8 ratio were improved,
      with a statistically significant difference. At 15 months after the operation,
      ten of the 19 patients (52.5%) satisfied the proposed criteria for clinical
      remission of RA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7801207
TI  - [Chronic fatigue syndrome: fictious or true disease?].

PMID- 7801208
TI  - Diuretic-induced dysmetabolism in the long-term management of hypertension.

PMID- 7801209
TI  - [New approaches in the treatment of prostatic cancer].

PMID- 7801210
TI  - [Kidney injuries in children].
AB  - Over the past 4 years 18 children were observed at the La Timone-Enfants Hospital
      in Marseille with renal lesions consequent to nonpenetrating abdominal traumas.
      Hematuria was reported in 14 cases (7 macroscopic and 7 microscopic) and all
      cases suffered from abdominal and/or lumbar pain. In relation to the diagnostic
      iter used: 18 echographies, 15 urographies, 13 TAC, 2 ascendant pyelographies, 2
      scintigraphies with DMSA, 1 echo-Doppler and one angiography were performed.
      Renal lesions were classified as: 8 type 1, 5 type 2, 4 type 3, 1 type 4. Four
      cases were operated and one case underwent percutaneous drainage of an
      urohematoma. Following an analysis of these case and a revision of the
      literature, the authors emphasise that the evolution and progress in the
      diagnosis and treatment of this important aspect of traumatic pathology in
      children enables an almost complete recovery of kidney function in almost all
      cases.

PMID- 7801211
TI  - [Urethro-vesical anastomosis after radical prostatectomy and bladder replacement
      with the Camey II approach].
AB  - Owing to its numerous biological characteristics, Tissucol fibrin cement is
      widely used in general and specialised surgery. In urology it is used on both the
      renal parenchyma and on the entire urinary tract. The authors report their
      experience regarding the use of Tissucol in the execution of urethro-vescical
      anastomosis during radical prostatectomy and cystectomy with orthotopic
      neovescica according to Camey II. A group of 25 patients were examined of whom 10
      with vescical neoplasia and 25 with cancer of the prostate. Anastomosis was
      always performed using four or five suture stitches in Dexon 2/0 and subsequently
      sealed with Tissucol. Suture condition was regularly checked using
      contrastography. The suture only gave way in one case of orthotopic neovescica
      with consequent urinary fistula; in all the other cases the anastomosis showed a
      perfect seal in both the short and long term. In the authors' opinion the good
      immediate result of anastomosis can significantly reduce the postoperative
      hospitalization.

PMID- 7801212
TI  - [Results of radiotherapy in patients with bladder carcinoma].
AB  - The authors analyse the results of treatment with radiotherapy with therapeutic
      doses and traditional fractionation scheme 60 patients affected by bladder
      cancer, from 1980 through 1991, at the Institute of Radiology of the University
      "La Sapienza" in Rome. We evaluated the association of radiotherapy (RT) with
      trans-urethral resection and biopsy (TURB) and the association of RT with
      cystectomy (total or partial), both in T1-T2 and T3-T4 bladder stages. The mean
      follow-up was 85 months (from 24 months to 11 years). The survival at 5 years
      after completing the treatment was 33.3%; the survival of stages T1-T2 was of 40%
      at 5 years while that of stages T3-T4 was of 28.5%. Our study shows that the
      association of radiotherapy and TURB for T1 or T2 bladder cancer is an
      alternative to mutilating surgery like total or partial cystectomy; in this
      group, indeed, we showed a survival of 54.5% at 5 years as compared to the 28.5%
      of the group treated with cystectomy + RT. For T3 and T4 bladder cancer we had
      better results with surgery (total or partial cystectomy) and RT: in these
      patients the survival at 5 years was of 31%, while the group treated with TURB +
      RT showed a survival of 19%.

PMID- 7801213
TI  - [Nosocomial urinary infections. Comparison of experience in two urology centers].
AB  - The authors analysed the type and the sensitivity of most common micro-organism
      causing urinary infections in the urological wards of Savigliano (CN) and Turin.
      In Savigliano, these data show a remarkable increase in the incidence of
      Pseudomonas; in the other urological ward the data show an increased incidence of
      E. coli. In Turin, the bacteria are more sensitive to antibiotics then in
      Savigliano.

PMID- 7801214
TI  - [Adrenal angioma simulating pheochromocytoma].
AB  - The authors report a case of adrenal angioma (a rare benign mesenchymal tumour)
      which was diagnosed by chance ("incidentaloma") and whose clinical and
      instrumental characterisation led to the hypothesis of a pheochromocytoma. The
      various diagnostic methods used are analysed together with results and the
      possible causes of their erroneous interpretation.

PMID- 7801215
TI  - Renal oncocytoma and renal pelvis carcinoma: a rare coexistence of double renal
      tumors.
AB  - We report a case of renal oncocytoma which was found incidentally during the
      nephroureterectomy for renal pelvis carcinoma. The coexistence of two tumors on
      the kidney with absolutely different origin one from the other is extremely rare
      and interesting. Herein we discuss the clinical, morphological, histological,
      ultrastructural and angiographical characteristics of oncocytoma.

PMID- 7801216
TI  - [Leiomyosarcoma of the spermatic cord. Case report and revision of the
      literature].
AB  - A 76 year old man presented with an asymptomatic, very big left scrotal mass that
      was found to be a leiomyosarcoma of the spermatic cord. It was treated by radical
      orchiectomy with ligation of the spermatic cord at the internal inguinal ring.
      Convalescence was uneventful. 6 months postoperatively there was no evidence of
      local recurrence of the neoplasm or distant metastasis.

PMID- 7801217
TI  - [Transperitoneal nephrectomy of crossed ectopic kidney without fusion associated
      with stenosis of the pyeloureteral junction and pyelocaliceal staghorn calculi].
AB  - The authors report their experience on a case of crossed ectopic kidney without
      fusion associated with stenosis of the pyeloureteral junction and secondary
      pyelocaliceal staghorn calculosis. After a brief summary of the various types of
      kidney ectopia and related principles of operation they describe their case
      report underlying the rarity of their case and the surgical approach. They
      consider the anterior transperitoneal approach as the most indicated for this
      type of malformation as it permits a better surgical view of the kidney and of
      the vascular structures.

PMID- 7801218
TI  - [Antibiotic sensitivity of bacterial strains isolated in the course of lower
      urinary tract infections. Comparison between two case series in different years].
AB  - Antibiotic susceptibility on 803 strains isolated from urine in 1990 and on 500
      strains isolated in 1978 have been tested. The comparison between the results on
      strains of the two periods confirm the utility of urine culture for cost
      effective treatments.

PMID- 7801219
TI  - Ophthalmic effects of low-energy laser irradiation.
AB  - Laser irradiation at subthreshold energies exerts various effects on the eye and
      other parts of the body, mainly the skin and nervous system, through a mechanism
      that has yet to be adequately explained. The ocular bioeffects are manifested
      mostly in the retina, but also in other ocular tissues. This review outlines the
      reported effects of low-energy laser irradiation on nonophthalmological tissues
      and organs, including those of the nervous system, with special emphasis on the
      optic nerve. It also details the ophthalmic phenomena induced by low-energy laser
      irradiation and examines claims of its therapeutic efficacy in several eye
      diseases, such as keratitis, glaucoma and macular degeneration.

PMID- 7801220
TI  - The vascular endothelium as a regulator of the ocular circulation: a new concept
      in ophthalmology?
AB  - The endothelium influences local vascular tone by releasing endothelium-derived
      relaxing factors such as nitric oxide, prostacyclin and a putative
      hyperpolarizing factor. In isolated ophthalmic arteries and the perfused eye, all
      endothelial factors importantly contribute to vascular regulation. In larger
      ophthalmic vessels, this is due to their effects on vascular smooth muscle cells;
      in smaller vessels, pericytes can be influenced as well. Contracting factors
      formed include peptide endothelin-1 and cyclooxygenase products, such as
      thromboxane A2 and prostaglandin H2. In the peripheral circulation endothelial
      dysfunction occurs under pathological conditions, both in conduit arteries and
      the microcirculation. An imbalance of endothelium-derived relaxing and
      contracting factors could be important for the development of vascular ophthalmic
      complications like hypertension, diabetes, arteriolosclerosis and retinal
      ischemia. Endothelial dysfunction may also contribute to vasospastic events in
      retinal migraine and some forms of low tension glaucoma associated with Raynaud
      phenomenon and migraine.

PMID- 7801222
TI  - Perforation of the globe during retrobulbar injection: medicolegal aspects of
      four cases.
AB  - Perforation or penetration of the globe is a risk of retrobulbar injection of
      anesthetic. Visual outcome following this complication depends on the severity of
      injury to the retina and on the physician's ability to promptly recognize and
      treat it. Four cases are presented to illustrate factors that contribute to
      proper management of this complication as well as to a favorable medicolegal
      position for the physician.

PMID- 7801221
TI  - Intraocular lymphoma presenting as retinal vasculitis.
AB  - We describe two unusual young patients with intraocular lymphoma who presented
      clinically with "retinal vasculitis." Brain biopsy specimens in both showed an
      angiocentric pattern of lymphocytic infiltration. Immunohistochemical studies
      were positive for T-cell markers. Both the retinal and the brain blood vessels
      were thus a preferential site of appearance of the malignant T-cells. Both cases
      responded favorably to aggressive chemotherapy with long-term survival. In the
      world's literature, there are 57 cases of intraocular lymphoma in which cell
      surface-marker studies were performed; of these, 53% proved to be B-cell
      lymphomas and 21% to be T-cell lymphomas. As more cases of intraocular lymphoma
      are studied with cell-typing and as our histochemical techniques improve, a
      correlation between the systemic and ocular findings and the cell type may be
      revealed.

PMID- 7801223
TI  - Is all nondefinable optic atrophy Leber's hereditary optic neuropathy?
AB  - Leber's hereditary optic neuropathy has been considered a bilateral, sequential
      hereditary optic neuropathy occurring overwhelmingly in young men. Until recently
      the diagnosis has been based on clinical criteria: severe loss of vision
      associated with central scotomas and classic ophthalmoscopic findings
      (circumpapillary telangiectatic microangiopathy, pseudoedema of the disk with
      absence of staining on fluorescein angiography, tortuous vessels in the early
      stages and eventually optic disk pallor). In 1988 a genetic mutation associated
      with Leber's hereditary optic neuropathy affecting mitochondrial DNA was
      recognized. Subsequently other mutations have been discovered as well. The
      ability to identify these patients technically has allowed us to recognize cases
      that do not fit our previous clinical criteria. One such case is presented and
      the question asked is whether the findings are related to the clinical course.

PMID- 7801224
TI  - Was Saint Paul struck blind and converted by lightning?
AB  - In the Bible, St. Paul (Saul of Tarsus) was struck blind by a light from heaven.
      Three days later his vision was restored by a "laying on of hands." The
      circumstances surrounding his blindness represent an important episode in the
      history of religion. Numerous theories have been proposed to account for this
      event which has been the subject of interest of theologians, philosophers,
      artists, and physicians. A lightning strike could explain all of the features of
      this episode. The proposal of a theory which correlates St. Paul's symptoms with
      contemporary scientific knowledge makes his recovery of vision and conversion no
      less miraculous or religiously significant since the theory demonstrates that,
      indeed, the event may have occurred exactly as stated in the Bible.

PMID- 7801225
TI  - Health care systems.

PMID- 7801226
TI  - El Greco's vision.

PMID- 7801227
TI  - Congenital optic disk anomalies.
AB  - Over the past decade, a wealth of information has accumulated pertaining to the
      diagnosis and management of patients with congenital optic disk anomalies. As new
      examples of each entity have been detailed, the diagnostic criteria for each
      anomaly have become more clearly defined. The advent of sophisticated noninvasive
      neuroimaging techniques has further refined our ability to accurately detect and
      categorize the associated CNS anomalies that complicate many of these conditions.
      In light of recent findings, this review will critically examine many of the well
      entrenched concepts pertaining to the diagnosis, evaluation, and treatment of
      patients with congenital optic disk anomalies. In so doing, it will attempt to
      dispel some longstanding misconceptions that pervade the literature and obscure
      our understanding of the pathogenesis, neuroradiological associations, and
      systemic implications of each anomaly.

PMID- 7801228
TI  - Characterization of human oro-facial and masticatory muscles with respect to
      fibre types, myosins and capillaries. Morphological, enzyme-histochemical, immuno
      histochemical and biochemical investigations.
AB  - This study provides a comparative characterization of four human oro-facial
      muscles, one masticatory muscle (the masseter) and two limb muscles, with respect
      to muscle fibre types, myosin isoforms and capillary supply. Enzyme-histochemical
      methods were used to evaluate the myofibrillar ATPase fibre type composition.
      Immuno-histochemical techniques were used to determine the expression of myosin
      heavy chain (MHC) isoforms in the different fibre types. The contents of MHCs and
      myosin light chains (MLC) in different muscles were analysed with electrophoretic
      methods. In addition, the capillary bed of the muscles was evaluated using both
      enzyme- and immuno-histochemical techniques. The fibre type compositions of the
      oro-facial and masseter muscles were found to be qualitatively and quantitatively
      different from each other and from those of limb muscles. In general, the oro
      facial muscles contained a predominance of unusually high oxidative type II
      fibres, with a staining reaction for ATPase in between that of type IIA and type
      IIB fibres, termed type IIAB. In fact, one of the oro-facial muscles, the
      zygomatic minor, showed the highest type II fibre proportion ever reported in
      humans. This fibre type pattern is in contrast to that of the masseter muscle,
      which contains a majority of type I fibres, small diameter low oxidative type IIB
      fibres and a significant proportion of ATPase-intermediately stained fibres,
      termed IM, and IIC. Inter- and intra-muscular variability in fibre size and shape
      was considerable in both the oro-facial and masseter muscles. The oro-facial
      muscles were devoid of muscle spindles. The immuno-histochemical and biochemical
      analyses showed a characteristic myosin composition of each muscle. Notably, the
      results indicated the presence of a previously undetected fast MHC isoform in the
      oro-facial muscles, tentatively termed "fast F". The masseter contained unusual
      myosin isoforms, such as fetal and alpha-cardiac MHCs, and unique combinations of
      MHC isoforms which were not found in the limb or oro-facial muscles. The type IM
      and IIC fibres co-expressed slow and fast A MHCs in the oro-facial and limb
      muscles, but slow and a "fast B like" MHC in the masseter. Individual fibres in
      the oro-facial and limb muscles contained one or two MHC isoforms, whereas
      individual fibres in the masseter co-expressed up to four different MHC isoforms.
      On the basis of their pattern of expression of MHC isoforms, up to five fibre
      types could be distinguished in the oro-facial and limb muscles and eight in the
      masseter.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7801231
TI  - [Congress: break with tradition].

PMID- 7801230
TI  - [Congress: with international greetings].

PMID- 7801229
TI  - Orthodontic magnets. A study of force and field pattern, biocompatibility and
      clinical effects.
AB  - Magnetic forces have been incorporated into orthodontic mechanics during recent
      years. However, the biocompatibility of magnet alloys and the possible risk of
      harmful or unusual reactions in tissues exposed to static magnetic fields have
      been characterized as inconsistent and often contradictory. It has also been
      questioned whether magnetic forces have significant advantages over traditional
      mechanics. The present series of studies aimed to analyse the force and field
      properties, the biocompatibility and the clinical effects of rare earth magnets
      as well as to compare the efficiency of tooth movement between magnets and
      another force system. Samarium-cobalt magnets for molar distalization were tested
      in experimental models for force and field properties. The cytotoxicity of
      different magnet alloys (rare earth types) as well as of clinically used and
      recycled magnets was assessed by two in vitro methods, the millipore filter
      method and an extraction method. The effect of static magnetic fields on human
      gingival tissue and dental pulp was examined histologically for alterations in
      cell pattern and cell morphology. The effects of using repelling samarium-cobalt
      magnets for simultaneous distalization of maxillary first and second molars were
      analysed in individuals with Class II malocclusion. The efficiency of molar
      distalization was also intra-individually compared between repelling magnets and
      superelastic NiTi-coils in individuals with Class II malocclusion and deep bite.
      The magnet forces decreased approximately with the reciprocal square of the
      separation distance between the magnets. No fatigue of force over time could be
      seen. The static magnetic fields were weak and had a limited extent and the flux
      density dropped exponentially in all directions with increased distance from the
      magnets, implying a small exposure area when the magnets are used clinically.
      Rare earth magnets showed good biocompatibility, particularly coated magnets.
      However, uncoated samarium-cobalt magnets showed significant cytotoxicity. It was
      also found that stainless-steel-coated samarium-cobalt magnets could be recycled
      with maintained good biocompatibility. After exposure to static magnetic fields,
      normal clinical and histological conditions in the human gingival tissue and
      normal histological features in the human dental pulp were found. Repelling
      magnets were effective in producing maxillary molar distalization but some side
      effects like anchorage loss and molar tipping were found. The superelastic coils
      were shown to be even more efficient than the repelling magnets for maxillary
      molar distalization in individuals with Class II malocclusion and deep bite.

PMID- 7801232
TI  - [Congress: we are the future].

PMID- 7801233
TI  - [Epidemiological research. Many fewer cases of crib death].

PMID- 7801234
TI  - [Quality assurance--the award for quality].

PMID- 7801235
TI  - [Research--can, will and dare to].

PMID- 7801237
TI  - [A better life for heart patients].

PMID- 7801236
TI  - [Research--in good company].

PMID- 7801238
TI  - [Family policy: healthy family--health society. Interview by Annagrethe Skov].

PMID- 7801239
TI  - [Chiropractic--treating both joints and muscles].

PMID- 7801240
TI  - [Congress: satisfy demands for playmates].

PMID- 7801241
TI  - [Quality assurance--performance must be measured. Interview by Kirsten
      Bjornsson].

PMID- 7801242
TI  - [The kind violation].

PMID- 7801243
TI  - [Patient complaints Board. Watch out!].

PMID- 7801244
TI  - [Congress: hostile discussions cause frustration].

PMID- 7801245
TI  - [Congress: patients without rights].

PMID- 7801246
TI  - [Congress: human rights must be safeguarded in organ donation].

PMID- 7801247
TI  - [Congress: contact network in technology].

PMID- 7801249
TI  - [Unemployment Insurance--more than 2000 on leave].

PMID- 7801248
TI  - [Congress: leave of absence popular].

PMID- 7801250
TI  - [Screening--prevention or overtreatment. Interview by Hanne Ried Larsen].

PMID- 7801251
TI  - [Romania--badly in need of better education].

PMID- 7801252
TI  - [Screening--the nodal breast. Interview by Hanne Ried Larsen].

PMID- 7801253
TI  - [Health policy--dangerous to be alive].

PMID- 7801254
TI  - [Time, that's us!].

PMID- 7801255
TI  - [Unfortunately your surgery has been canceled].

PMID- 7801256
TI  - [A beautiful ending--nursing stories].

PMID- 7801257
TI  - [Nursing stories--thanks for your time].

PMID- 7801259
TI  - [Congress: against privatization in the primary care sector].

PMID- 7801258
TI  - [Congress: for poor cooperation].

PMID- 7801260
TI  - [Congress: discount health care].

PMID- 7801261
TI  - [Congress: hopeless conditions in psychiatry].

PMID- 7801262
TI  - [A loyal second fiddle. Interview by Mette Fjordbo].

PMID- 7801264
TI  - [Higher permanent salaries to private employees].

PMID- 7801263
TI  - [Executive Board: wages and risk].

PMID- 7801265
TI  - [Care for the elderly--they would like to go home--but they are staying].

PMID- 7801266
TI  - [Work environment--there will be 2 with a lifting injury].

PMID- 7801267
TI  - [Greenland--nurse in Egedesminde].

PMID- 7801268
TI  - [Health policy--neglected prevention].

PMID- 7801270
TI  - [In the name of health].

PMID- 7801269
TI  - [Patient report--an inhumane system].

PMID- 7801271
TI  - [Nursing stories: life changes within a few minutes].

PMID- 7801272
TI  - [Joint management--professional identity needed].

PMID- 7801274
TI  - [Congress: a work environment with pressure].

PMID- 7801273
TI  - [Home care--network or a mess?].

PMID- 7801275
TI  - [Congress: discussion about journal filled with conflict of interest].

PMID- 7801276
TI  - [Congress: organization's foundation stone].

PMID- 7801277
TI  - [Overcrowding: quickly in--quickly out].

PMID- 7801278
TI  - [Education--the first litter faces reality].

PMID- 7801279
TI  - [Health policy--development costs money].

PMID- 7801280
TI  - [Technology assessment--we are treating in the dark].

PMID- 7801281
TI  - [Joint management--the good question].

PMID- 7801282
TI  - [History--collecting goes ahead].

PMID- 7801283
TI  - [Adoption--a possibility not to be overlooked].

PMID- 7801284
TI  - [Drilling platform--on an island in the North Sea. Interview by Randi Sandbeck].

PMID- 7801285
TI  - [Planning for health].

PMID- 7801287
TI  - [Professional secrecy--patients' and employees' freedom of speech].

PMID- 7801286
TI  - [Professional secrecy--those slippery journalists].

PMID- 7801289
TI  - [Handcuffs closed according to ratchet principle].

PMID- 7801288
TI  - [Paralysis and fractures].

PMID- 7801290
TI  - [Invisible nursing care].

PMID- 7801291
TI  - [Nursing care--here's where research starts].

PMID- 7801293
TI  - [Supply and demand].

PMID- 7801292
TI  - [Joint management. Hands and gloves should fit together].

PMID- 7801294
TI  - [Health policy--continuously well-functioning].

PMID- 7801295
TI  - [Are handcuffs used as punishment?].

PMID- 7801296
TI  - [Nerve injuries due to handcuffs].

PMID- 7801297
TI  - Optic nerve hypoplasia: comparative effects in children and rats exposed to
      alcohol during pregnancy.
AB  - Children with the fetal alcohol syndrome often have ocular anomalies. These
      include abnormalities of the eyes and adnexa (strabismus, blepharoptosis,
      epicanthus), as well as intraocular defects (cataract, glaucoma, persistent
      hyperplastic primary vitreous, retinal and optic nerve anomalies). Based on the
      clinical results in an ophthalmological study of a group of Swedish children with
      the fetal alcohol syndrome, in which optic nerve hypoplasia was found in up to
      one-half of the group, an experimental study was designed in rats pre- and
      perinatally exposed to alcohol by means of a liquid diet. The optic nerve was
      seriously affected. Macroglial cells and optic axons were ultrastructurally
      damaged. The diameter of the optic nerve cross section, glial cell nuclear area,
      axonal diameter, and the total number of optic axons showed significantly lower
      values in the alcohol-exposed group than in the controls. In addition, the retina
      from the alcohol-exposed animals displayed significantly lower values of the
      retinal thickness and ganglion cell nuclear volume, as compared to the controls.
      Thus, rats exposed to alcohol in utero developed hypoplasia of the optic nerve
      similar to the findings in children born to alcoholic mothers. This strongly
      supports the hypothesis that prenatal alcohol exposure may adversely affect the
      development of the optic nerve.

PMID- 7801299
TI  - Early sialylation on N-CAM in splotch neural tube defect mouse embryos.
AB  - The splotch (Sp) mutant mouse is a model for neural tube defects and Waardenburg
      syndrome type I. The neural tube defects that arise in Sp, which include spina
      bifida and exencephaly, are thought to be caused by a change in the timing of the
      cellular events which are taking place during neurulation. Cell adhesion
      molecules are strongly implicated in a variety of cell-cell interactions
      throughout development, thus the neural cell adhesion molecule (N-CAM) may play a
      role in neural tube formation and closure. The N-CAM in day 9 Sp embryos is
      altered showing a heavy 200 kD species rather than the 180 and 140 kD isoforms
      which are normally present at that developmental stage [Moase and Trasler (1991)
      Development 113:1049-1058]. These N-CAM isoforms normally become modified post
      translationally by the addition of alpha-2,8 linked polysialosyl (PSA) units
      beginning at gestational day 11. Sp/Sp, Sp/+, and +/+ embryos were examined by
      Western blot analysis with an antibody (mAb 5A5) which specifically recognizes
      PSA residues on N-CAM. Mutant and heterozygote embryos display a sialylated N-CAM
      form at 20, 14, and 12 somite-stages which is absent in controls. Enzymatic
      removal of PSA on N-CAM resulted in a reduction of the 200 kD PSA-free N-CAM
      isoforms. These results in the observed 200 kD species, and suggest that the Sp
      gene is involved in the regulation of expression or the post-translational
      modification of N-CAM.

PMID- 7801298
TI  - Risk factors for hypoplastic left heart syndrome.
AB  - A case-control study was performed in Finland to investigate the etiology of the
      lethal heart malformation, hypoplastic left heart syndrome (HLHS). The cases
      represented all verified HLHS (n = 34) in Finland during 1982-1983, and controls
      (n = 756) were randomly selected from all babies born during the same period.
      Both case and control mothers were interviewed by midwives approximately 3 mo
      after delivery. Maternal upper respiratory infection during the first trimester
      of pregnancy was a significant risk factor for HLHS (OR = 2.5, Cl95 = 1.2-5.4).
      Maternal exposures at work to factors such as disinfectants, pesticides, dyes,
      lacquers or paints, and anesthetic gases were rare and failed to indicate any
      risk for HLHS. Maternal use of deodorants or hairsprays during the first
      trimester of pregnancy was not a significant risk factor for HLHS (OR = 1.8, Cl95
      = 0.9-3.6). The risk of HLHS was not associated with seasonal variation, maternal
      smoking, alcohol or coffee consumption, or use of acetosalicylic acid. Because
      the study material is limited in size, the power of this investigation is weak
      for testing the teratogenicity of specific chemicals on the risk of HLHS. Thus,
      conclusions from the negative findings of this study should be drawn very
      carefully.

PMID- 7801300
TI  - Prenatal neuroleptic exposure and growth stunting in the rat: an in vivo and in
      vitro examination of sensitive periods and possible mechanisms.
AB  - There is increasing evidence that a number of neurotransmitters can play a
      trophic role in the development of the central nervous system. Dopamine is one
      candidate for this role. In a series of papers, Lewis, Patel, and colleagues have
      demonstrated that exposure to compounds which interfere with dopaminergic
      neurotransmission ("neuroleptics") can block cell proliferation in the brains of
      11-day-old rat pups for at least 24 hr. More recently our laboratory has reported
      that prenatal exposure to haloperidol (HAL), a neuroleptic which binds to and
      blocks dopamine receptor sites in the adult brain, permanently stunts body and
      brain growth when that exposure extends throughout postimplantation pregnancy.
      Reported here are the results of two experiments conducted to further examine
      this phenomenon. The first experiment attempted to identify sensitive gestational
      periods for the HAL effect on growth in vivo. This experiment also assessed the
      effect of exposure to reserpine (RES), a compound which in the adult blocks
      dopaminergic neurotransmission by rupturing monoamine storage vesicles, an effect
      which is quite distinct from the HAL mechanism of action. In a second experiment,
      gestational day (GD) 9 embryos were exposed in vitro for 48 hr to either HAL,
      RES, or one of two specific blockers of dopamine receptor subtypes. Schering
      23390 (SCH) was used as the D1 blocker, and sulpiride (SULP) as the D2 blocker.
      The in vivo experiment showed that twice-daily exposure to subcutaneous
      injections of HAL (5 mg/kg for each of the 2 injections) or RES (0.1 mg/kg for
      each injection) permanently stunted brain growth when injections were given in
      midpregnancy (GD 12-16), but not in late pregnancy (GD 16-20). RES was
      substantially more fetotoxic than HAL, especially late in pregnancy. The growth
      stunting produced by either compound with GD 12-16 exposure was not restricted to
      dopamine-rich areas of the brain, or indeed to the brain itself, in that body
      weight was also depressed. Pair-fed controls did not show the same magnitude or
      duration of stunting, indicating that this effect was not due to drug-induced
      maternal hypophagia. The in vitro experiment revealed that exposure to micromolar
      concentrations of any of the 4 neuroleptics reduced embryonic GD 11 DNA and
      protein content and delayed development. HAL and SCH had the most pronounced
      effects at concentrations close to blood levels reportedly produced by exposure
      to doses used in the in vivo experiments. RES was less potent, and SULP still
      less potent than RES.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7801301
TI  - Ebstein's malformation of the tricuspid valve: genetic and environmental factors.
      The Baltimore-Washington Infant Study Group.
AB  - Ebstein's anomaly is a specific structural deformity of the tricuspid valve, and
      its rarity has hampered etiologic evaluation. Cases of Ebstein's anomaly
      registered in the Baltimore Washington Infant Study (BWIS), a regional case
      control study of cardiovascular malformations (CVM) in infancy, are reviewed.
      Between 1981 and 1989 a total of 4,390 CVM cases, including 47 Ebstein cases, and
      3,572 controls were registered. The prevalence of Ebstein's anomaly was 5.2 per
      100,000 livebirths. Additional cardiac anomalies were present in 38.3% of Ebstein
      cases. Non-cardiac malformations were present in 19.1% of Ebstein cases vs. 25.5%
      of other CVM, and 1.7% of controls. Case-fatality by 1 year of age was 23.4% in
      Ebstein vs. 18.1% in other CVM. Interviews of parents of Ebstein cases, other
      CVM, and controls (n = 44, 3,335, and 3,572, respectively) elicited information
      on family history of malformations, maternal illnesses, reproductive history,
      therapeutic drugs, parental lifestyle, and environmental exposures during the
      periconceptional period. Case-control analyses suggest genetic, reproductive, and
      environmental risk factors: twins [odds ratio (OR) 8.2, 95% confidence interval
      (CI) 2.6-25.3]; family history of CVM (OR 6.4, 95% CI 1.8-22.2); white race (OR
      2.9 with non-whites as reference, 95% CI 1.2-7.0); previous miscarriages (OR 2.0,
      95% CI 1.2-3.3); maternal exposure to benzodiazepines (OR 5.4, 95% CI 1.5-19.1);
      and varnishing (OR 3.4, 95% CI 1.3-9.1). Additional multicenter investigations
      are warranted to elucidate the role of genetic, reproductive, and environmental
      factors in the etiology of this anomaly.

PMID- 7801302
TI  - Selenium kinetics, placental transfer, and neonatal exposure in cynomolgus
      macaques (Macaca fascicularis).
AB  - Forty pregnant cynomolgus macaques were treated daily from gestational day 20 to
      50 by nasogastric intubation of 0, 25, 150, or 300 micrograms selenium as L
      selenomethionine/kg body weight. In each group, 7-8 pregnancies were terminated
      by hysterotomy at gestational day 100 +/- 2 and the fetuses were examined, while
      2-3 pregnancies in each group were allowed to proceed to term. Selenium and
      soluble glutathione peroxidase were measured in: maternal, neonatal, and fetal
      plasma and erythrocytes; fetal kidney, liver, muscle, and placenta; and maternal
      breast milk. The area under the multidose maternal plasma selenium
      concentration:time curve, the maximum maternal plasma selenium concentration, and
      the maternal urinary selenium excretion rates were proportional to the L
      selenomethionine dose. Selenium concentrations in all fetal and neonatal, tissues
      were also proportional to maternal L-selenomethionine dose. Glutathione
      peroxidase was affected only in maternal erythrocytes, fetal kidney, and neonatal
      plasma. The selenium concentration in fetal plasma was an average 33% of that in
      maternal plasma. Although selenium concentrations in macaque milk were doubled by
      the highest dose, intrauterine selenium accumulation accounted for the majority
      of the neonatal selenium body burden. Despite the elevated selenium
      concentrations in fetal tissues, neonatal blood, and milk, no deleterious effects
      on neonates were observed. These results suggest that primate fetuses are well
      protected against selenium toxicity arising from high maternal L-selenomethionine
      intakes.

PMID- 7801303
TI  - Unusual craniofacial dysmorphia due to prenatal alcohol and cocaine exposure.

PMID- 7801304
TI  - Placental teratoma with three-germ layer differentiation.
AB  - A rare case of placental teratoma is described. Major features were the
      presentation as a pedunculated mass from the fetal surface of the placenta, the
      mixture of different tissues derived from all three germ layers (skin with dermal
      appendages, ganglion-like cells, and nervous structures, gut structures,
      osteocartilagineous and smooth and striated muscle), and the absence of segmental
      organization.

PMID- 7801305
TI  - A fetus with sirenomelia, omphalocele, and meningomyelocele, but normal kidneys.
AB  - Sirenomelia, which has been reported for more than 450 years, is the most severe
      form of caudal dysplasia. This disorder is classically associated with agenesis
      or severe dysplasia of the urinary tract. A 27-year-old gravida 3 para 0020
      presented at 19 weeks' gestation with monoamniotic twins, one normal and one with
      sirenomelia. The pregnancy miscarried following invasive diagnostic testing.
      Autopsy confirmed the findings of sirenomelia, meningomyelocele, omphalocele,
      persistent cloaca, and two normal kidneys. The abnormalities accompanying
      sirenomelia appear as a spectrum. The pathogenic theories of sirenomelia are
      reviewed in light of this case with normal kidneys.

PMID- 7801306
TI  - "Proof" of human teratogenicity.

PMID- 7801307
TI  - Review of interactions in developmental toxicology.

PMID- 7801308
TI  - [The changing role of the veterinarian in primary production (demands with
      respect to diagnostic tests, risk analysis and the need for certification of
      farms)].
AB  - Various new developments in livestock production confront the veterinarian. In
      addition to Integrated Food Chain Quality Control, certification of farms for
      animal health status and also for production methods is becoming increasingly
      important. Certification for veterinary practices is forthcoming. In order to
      optimize national herd health, quantitative information is needed and certain
      methods have to be improved. The veterinarian must be able to apply new
      techniques adequately and to interpret disease- and environment-related data
      properly. Problem areas are highlighted and different ways of dealing with them
      are elaborated upon. It is concluded that the veterinarian is strategically
      positioned to solve these problems, but that suitable, complementary training is
      needed, as well as new quantitative research.

PMID- 7801309
TI  - [Differential diagnosis of non-healing 'fungal'patches in horses].
AB  - Dermatophytosis is the most common equine skin disease. Mycotic-like lesions that
      do not disappear are suspected of being sarcoids. The clinical symptoms and
      therapeutic interventions for both affections are discussed. A short review of
      the differential diagnoses is presented.

PMID- 7801310
TI  - [Red Cross veterinary program in Somalia].

PMID- 7801311
TI  - [Establishment of the Bureau side effects animal drugs].

PMID- 7801312
TI  - [VVAA accident insurance--HIV infection and violence covered].

PMID- 7801314
TI  - [Veterinary medicine in 2000].

PMID- 7801313
TI  - [Warning: sedatives for pets, effect on their master].

PMID- 7801315
TI  - [Dogs with ascites].

PMID- 7801316
TI  - Induction by melittin of protein phosphorylation in bovine mammary gland and
      suppression of the phosphorylation by phosphatidylserine.
AB  - The protein kinase C (PKC) inhibitor sphingosine induces phosphorylation of an 18
      kDa protein in Jurkat T cells and of a 19-kDa protein in bovine mammary gland,
      and suppresses phosphorylation of substrate proteins for PKC. Melittin, a toxic
      amphiphilic peptide from bee venom known to inhibit PKC activity, was examined to
      determine whether it, like sphingosine, induced phosphorylation of the 19-kDa
      protein. Melittin inhibited PKC activity in both cytosolic and total particulate
      fractions of bovine mammary gland, with IC50 values (concentrations causing 50%
      inhibition) of 5-7 microM. Melittin suppressed phosphorylation of such PKC
      substrate proteins as a 91-kDa protein in cytosol and a 36-kDa protein in the
      particulate fraction. Besides the suppression, melittin induced phosphorylation
      of cytosolic 105-kDa, 94-kDa, 27-kDa, 24-kDa and 19-kDa and particulate 110-kDa,
      53-kDa and 43-kDa proteins, which were not clearly observed in the absence of
      melittin. The induction could be detected at a 10 microM concentration.
      Phosphorylation of these proteins was reversed by excess addition of the PKC
      cofactor phosphatidylserine, but not by other cofactors such as 1-oleoyl-2-acetyl
      sn-glycerol or Ca2+. PKC inhibitors other than melittin [1-(5
      isoquinolinylsulfonyl)-2-methyl-piperazine, gossypol, palmitoylcarnitine and
      adriamycin] had little effect on the induction, except at a high concentration
      (500 microM) of adriamycin. These results suggest that melittin, like
      sphingosine, has both suppressive and stimulatory effects on protein
      phosphorylation in bovine mammary gland.

PMID- 7801317
TI  - Demethylation and placental transfer of methyl mercury in the pregnant hamster.
AB  - The demethylation and placental transfer of methylmercury (MeHg) was studied in
      Syrian Golden hamsters administered a single oral dose of 203Hg-labeled MeHgCl,
      1.6 mumol/kg body weight, on day 2 or 9 of gestation and sacrificed 1 day before
      expected parturition. In order to evaluate the role of demethylation for
      transplacental transport of MeHg, four hamsters were administered 203Hg-labeled
      HgCl2 intravenously on day 9 of gestation. The mean biological halftime of 203Hg
      in animals administered radiolabeled MeHg was 7.7 days and the fecal route was
      the main excretory pathway. The fetal content of 203Hg in hamsters administered
      radiolabeled MeHg on gestational day 2 or 9 corresponded to 1.3% and 4.6% of the
      administered dose, respectively. The distribution of 203Hg in the fetus was more
      even than in the dam and the concentration of 203Hg in the fetal brain, liver and
      kidney was similar to that of the placenta. Inorganic Hg was found in maternal
      liver (18% of total Hg), kidney (31%) and placenta (21%) and fetal liver (3%).
      The amount of inorganic 203Hg in fetal liver corresponded to about 0.015% of the
      dose administered to the dam as MeHg. When hamsters were administered 203HgCl2 by
      intravenous injection on day 9 of gestation, the concentration of 203Hg in fetal
      liver corresponded to 0.03% of the administered dose. The inorganic 203Hg
      detected in fetal liver after maternal exposure to MeHg was probably due to
      demethylation of MeHg in the dam and transplacental transfer of inorganic Hg.

PMID- 7801318
TI  - Stressor-specific induction of heat shock proteins in rat hepatoma cells.
AB  - In order to determine whether induction of specific stress proteins is dependent
      on a given stressor and whether induction of these proteins is linked to
      survival, Reuber H35 rat hepatoma cells were exposed to five different
      environmental stressors (heat shock, arsenite, cadmium, dinitrophenol and
      ethanol). The effect of these stressors was studied on cell survival as well as
      on inhibition and recovery of protein synthesis and on induction of heat shock
      proteins (hsps). In this article, we present evidence that several well-known hsp
      inducers fail to stimulate specific hsps in a degree that is comparable to the
      induction of these hsps by heat shock. Most evidently, hsp60 is not induced by
      cadmium-treatment, whereas hsp100 is hardly induced by sodium arsenite. Treatment
      with DNP only slightly induces hsp68 and hsp84, whereas no detectable induction
      of hsps is observed after treatment with ethanol. In contrast, treatment with
      cadmium raises the amount of hsp28 to a higher level as compared to heat shock. A
      comparison of the stressor-specific induction of major hsps was also made under
      conditions of similar impact on cellular physiology: (a) stressor conditions up
      to the critical point that cell death starts to occur, and (b) conditions of iso
      survival (50%). We conclude that hsps cannot be simply used as a general risk
      assessment tool, and that the validation of stressor-specific risk-assessment
      warrants further research with larger groups of proteins.

PMID- 7801319
TI  - Cadmium-induced alteration of glycosaminoglycans with an enhancement of heparin
      like activity in cultured vascular endothelial cells.
AB  - Glycosaminoglycans (GAGs), especially heparan sulfate, are involved in the
      anticoagulant property of vascular endothelium. It was observed that heparin-like
      activity on the surface of cultured bovine aortic endothelial cells was enhanced
      by cadmium at 1.0 microM or more after a 24-h incubation. The incorporation of
      [3H]glucosamine into GAGs, a marker of GAG synthesis, was markedly increased by
      cadmium at 0.5 microM or more in both the cell layer and the conditioned medium;
      however, the incorporation of [35S]sulfate, a marker of the GAG sulfation, was
      significantly reduced by the metal at 2.0 microM or more. Similar changes were
      observed in a cultured human umbilical vein endothelial cell layer.
      Characterization of GAGs in bovine endothelial cell layer revealed that cadmium
      (2.0 microM)-induced alterations mostly occurred in the major component heparan
      sulfate rather than in other minor GAGs. Stimulation of [3H]glucosamine
      incorporation by cadmium at 2.0 microM occurred even in the presence of p
      nitrophenyl-beta-D-xyloside but disappeared in the presence of cycloheximide,
      suggesting that cadmium might induce the production of proteins which are
      involved in GAG synthesis. The present data suggest that vascular endothelial
      cells are capable of enhancing the potential anticoagulant activity on their
      surface via induction of heparan sulfate synthesis. This response of endothelial
      cells may be a defensive one to the procoagulant state of blood which can be
      induced by cadmium.

PMID- 7801320
TI  - Mixtures of benomyl, pirimiphos-methyl, dimethoate, diazinon and azinphos-methyl
      affect protein synthesis in HL-60 cells differently.
AB  - Dimethoate, azinphos-methyl, diazinon and pirimiphos-methyl, widely used
      organophosphorous insecticides, and benomyl, a benzimidazole fungicide, induce
      different cytotoxic effects on the human leukemia cell line HL-60. Among the
      insecticides tested, only azinphos and diazinon induced a dose-related inhibition
      of protein synthesis in HL-60 cells at 24 h, at 60 and 40 micrograms/ml medium,
      respectively. Dimethoate and pirimiphos were not active up to 100 micrograms/ml.
      Benomyl strongly inhibited protein synthesis at 50 micrograms/ml and the
      polymerisation of actin to give cytoskeletal microfilaments (F-actin) at 30
      micrograms/ml. Mixtures of benomyl-pirimiphos and dimethoate azinphos-diazinon
      were also investigated. Pirimiphos, when present in equal concentration,
      antagonized the inhibitory effect of benomyl on protein synthesis at 4 h, but not
      at 24 h. The effect of the other insecticide mixture on the same parameter was
      greater than that of the two active components, diazinon and azinphos given
      singly.

PMID- 7801321
TI  - Pharmacodynamic and metabolic interactions between ethanol and two industrial
      solvents (methyl n-butyl ketone and methyl isobutyl ketone) and their principal
      metabolites in mice.
AB  - MnBK and MiBK prolong the duration of ketamine-, pentobarbital-, thiopental- and
      ethanol-induced loss of righting reflex (LRR) in mice. In equimolar doses, (5
      mmol/kg i.p.), both isomers were equipotent with respect to the enhancement of
      ketamine-, pentobarbital-, and thiopental-induced LRR. However, MnBK was
      significantly more effective (twice as effective) than its isomer with respect to
      enhancing ethanol-induced LRR. An attempt to explain the difference in
      effectiveness between the two isomers was carried out. The effects of both
      ketones and their principal metabolites, (2-hexanol (2-HOL), 2,5-hexanedione (2,5
      HD), 4-methyl-2-pentanol (4-MPOL) and 4-hydroxy 4-methyl-2-pentanone (HMP)) on
      ethanol-induced LRR and ethanol elimination were studied in mice. The ketones and
      their metabolites were dissolved in corn oil and injected intraperitoneally 30
      min before 4 g/kg ethanol for LRR and 2 g/kg for ethanol elimination. Ethanol
      induced LRR was significantly prolonged by the following dosages (mmol/kg), MnBK,
      5; MiBK, 5; 2-HOL, 2.5; 4-MPOL, 2.5; and HMP, 2.5; 2,5-HD, 2.5, however exerted
      no effect. Concentrations of ethanol in blood or brain upon return of the
      righting reflex were similar in solvent-treated and control animals. The mean
      elimination rate of ethanol was slower in groups pretreated with MnBK or 2-HOL as
      compared to control animals. Ethanol elimination in animals pretreated with MiBK,
      HMP, 4-MPOL, or 2,5-HD was similar to that in control animals. These ketones are
      known to have some central depressant action on their own. This by itself could
      lead to prolongation of ethanol-induced LRR. However, MnBK, as well as one of its
      principal metabolites, (2-HOL), markedly reduced ethanol elimination. This could
      explain the observation that MnBK has a greater potentiating effect on ethanol
      induced LRR that its isomer, MiBK, which does not affect ethanol elimination.

PMID- 7801322
TI  - Thyroxine normalizes polychlorinated biphenyl (PCB) dose-related depression of
      choline acetyltransferase (ChAT) activity in hippocampus and basal forebrain of
      15-day-old rats.
AB  - Neonatal exposure to the toxic chemical polychlorinated biphenyl (PCB) induces
      hypothyroidism (depressed thyroid hormones). Neonatal rats made hypothyroid by
      other means (chemical or surgical) have subnormal activity of choline
      acetyltransferase (ChAT), which catalyzes synthesis of acetylcholine, in the
      hippocampus and basal forebrain. The present study examined whether neonatal rats
      with PCB-induced hypothyroidism had depressed ChAT activity in these two brain
      areas, and whether alterations in ChAT activity were secondary to hypothyroidism
      rather than/in addition to a direct effect of PCB. Neonatal rats were exposed to
      PCB by feeding pregnant female rats chow containing various concentrations of PCB
      (0, 62.5, 125 or 250 ppm) throughout pregnancy and lactation. During postnatal
      days 4-14, neonatal rats exposed to the highest concentration of PCB were
      injected with either saline, triiodothyronine (T3), or thyroxine (T4), or were
      not injected at all. Circulating thyroid hormone levels (T4 and T3) and brain
      ChAT activity were determined at 15 days of age. All concentrations of PCB
      depressed circulating T4 levels and ChAT activity in a dose-response manner, but
      did not modify T3 levels. Injections of T4, but not T3, elevated ChAT activity in
      PCB-exposed rats to near control levels. Thus, altered ChAT activity in PCB
      exposed rats may partially result from the hypothyroidism accompanying PCB
      poisoning. The possible molecular mechanism(s) of action of PCB on brain ChAT
      activity remains unclear.

PMID- 7801323
TI  - Reduction of thyroxine uptake into cerebrospinal fluid and rat brain by
      hexachlorobenzene and pentachlorophenol.
AB  - In the present study the effects of hexachlorobenzene (HCB) and the metabolite
      pentachlorophenol (PCP) were investigated with respect to uptake of thyroxine
      (T4) into cerebrospinal fluid (CSF) and brain structures of rats. [125I]T4 was
      taken up into CSF of control rats by a relatively slow process, reaching a steady
      state after about 3 h. Both repeated dosing of HCB and single doses of PCP caused
      decreased uptake of [125I]T4 into CSF, total brain tissue as well as specific
      brain structures, such as occipital cortex, thalamus, and hippocampus. Although
      HCB-treatment caused a build-up of HCB and PCP levels in serum in brain only HCB
      was present in significant amounts (16% of the serum level). In CSF, both HCB and
      PCP concentrations were below detection levels. Separate experiments with PCP
      showed, however, a dose- and time-dependent uptake of PCP into CSF. The present
      results indicate that PCP and the parent compound HCB are able to affect brain
      supply of T4. This may have consequences for an adequate development of the brain
      or proper brain function in adults. The exact mechanisms of interference of PCP
      and/or HCB in brain uptake of T4 remain to be established.

PMID- 7801324
TI  - Role of metabolism in monocrotaline-induced immunotoxicity in C57BL/6 mice.
AB  - Monocrotaline (MCT) is a pyrrolizidine alkaloid which has been shown to induce
      immunotoxicity in mice. We hypothesized that metabolic activation of MCT by mixed
      function oxygenases (MFO) to dehydromonocrotaline (MCTP) is a prerequisite for
      its immunotoxicity, as has been shown for other toxic effects of MCT. To test
      this hypothesis, we compared the in vitro immunotoxic potency of MCT and MCTP to
      suppress the in vitro antibody response to SRBC and the blastogenic response to B
      and T cell mitogens. In addition, the effects of in vivo modulation of MFO
      activities on the immunotoxicity of MCT was examined using phenobarbital (PB) to
      increase and chloramphenicol (CP) to decrease MCTP production. Results showed
      that in vitro exposure of splenic lymphocytes to MCT or MCTP produced significant
      suppression of the antibody and blastogenic responses. MCTP was 200-400-fold more
      potent than MCT. No metabolism of MCT by splenic cells was detectable, suggesting
      that unmetabolized MCT is capable of inducing immunotoxicity. In vivo studies
      showed that, while treatment of mice with PB or CP produced significantly
      increased and decreased MCTP production by liver microsomes, neither PB or CP
      treatment significantly altered the immunotoxic potency of MCT. Thus, while the
      MCTP metabolite is directly immunotoxic in vitro and much more potent than MCT, a
      role for the MCTP metabolite in MCT immunotoxicity in vivo could not be
      demonstrated.

PMID- 7801325
TI  - Impaired host resistance to Trichinella spiralis as a consequence of prenatal
      treatment of rats with diazepam.
AB  - In utero exposure of Long Evans rats to low dosages of diazepam has previously
      been found to result in depression of cellular and humoral immune responses until
      adulthood, with marked changes in cytokine release by splenocytes and splenic
      macrophages. In order to assess the significance of these alterations in immune
      cells with regard to host resistance, we investigated the resistance of adult
      offspring towards Trichinella spiralis. Time-pregnant rats were treated with
      diazepam (1.25 mg/kg/day) or vehicle from gestational day 14 to 20. Male
      offspring were infected with T. spiralis at 2 months of age. This infection model
      tests the participation of T- and B-cell populations and of macrophages.
      Prenatally diazepam-exposed animals exhibited an impaired defence towards T.
      spiralis. The number of muscle larvae was increased as determined in digested
      carcasses and by morphometric analysis of the tongue. Moreover, antibody titers
      were altered, i.e., IgG was decreased and IgA was elevated in the prenatally
      diazepam-exposed group. These results demonstrate an impaired defense towards T.
      spiralis in adult rats after prenatal exposure to diazepam.

PMID- 7801326
TI  - Immune parameters are affected differently after cyclosporine A exposure in
      Fischer 344 rats and B6C3F1 mice: implications for immunotoxicology.
AB  - Knowledge of interspecies differences, commonly evaluated in other disciplines
      such as carcinogenesis, is a prerequisite for an appropriate assessment of
      immunotoxicological risks. The purpose of this study was to assess interspecies
      differences following exposure of Fischer 344 rats and B6C3F1 mice to
      cyclosporine A. These animals were exposed daily to cyclosporine A by oral gavage
      at 0, 5, 10, 25 mg/kg/day for 14 consecutive days. The results showed that
      splenocytes lymphoproliferation in response to concanavalin A or
      phytohemagglutinin, and IgM antibody-forming cells to sheep red blood cells, were
      affected in both species. Cytotoxic T-lymphocyte activity and mixed lymphocyte
      response were significantly inhibited in the rat following cyclosporine A
      exposure while they remained unaffected in the mouse. In contrast, natural killer
      cell activity was significantly depressed in the B6C3F1 mouse but not in the
      Fischer 344 rat. The discrepancies between the two species in cytotoxic T
      lymphocyte activity and mixed lymphocyte response assays could partially be
      explained by the constantly higher blood level of cyclosporine A in the rat than
      in the mouse. When these tests were performed using rat and mouse splenocytes
      exposed to cyclosporin A in vitro (10(-9) to 10(-5) M) it was possible to
      correlate in vivo and in vitro data for concanavalin A- and phytohemagglutinin
      induced lymphoproliferation and for cytotoxic T-lymphocyte activity but not for
      mixed lymphocyte response. Natural killer activity was 10-fold more sensitive in
      mice than in rats in vitro but these results did not clarify the in vivo
      difference. In conclusion, these results emphasize that the utilization of more
      than one species should be considered when assessing immunotoxicity.

PMID- 7801327
TI  - Toxicity of bromodichloromethane in female rats and mice after repeated oral
      dosing.
AB  - The carcinogenic water disinfection byproduct, bromodichloromethane (BDCM),
      produces renal and hepatic toxicity in rodents in acute and subchronic studies.
      In the present investigation, female rats and mice (n = 6) were dosed daily for 5
      consecutive days with BDCM (dissolved in an aqueous, 10% Emulphor solution) by
      gavage. Rats received 75, 150 and 300 mg BDCM/kg body weight/day and mice
      received 75 and 150 mg BDCM/kg body weight/day. Two rats in the 300 mg/kg/day
      treatment group died on day 5. On day 6, the animals were sacrificed and serum
      samples were taken for analysis of indicators of hepatic and renal toxicity.
      Livers and kidneys were excised and samples taken for histopathological
      evaluation. Portions of the livers were also utilized to produce microsomes for
      analysis of cytochrome P450 enzyme activities and total P450 content. Total
      hepatic cytochrome P450 was decreased in rats dosed with 150 and 300 mg BDCM/kg
      body weight/day, but was not significantly affected in BDCM-treated mice. Serum
      lactate (LDH) and sorbitol (SDH) dehydrogenase, aspartate aminotransferase (AST),
      creatinine and blood urea nitrogen were increased above those of controls in rats
      dosed with 300 mg BDCM/kg/day. These data suggested that hepatic and renal damage
      had occurred in this treatment group. This was confirmed by histopathological
      analyses which revealed that lesions occurred in both hepatic and renal tissues
      from rats dosed with 150 and 300 mg BDCM/kg/day. The hepatic lesions were
      centrilobular and primarily consisted of vacuolar degeneration. The
      hepatotoxicity indicators alanine aminotransferase (ALT) and SDH were increased
      in mice dosed with 150 mg BDCM/kg/day. However, no histopathological lesions were
      observed in these animals. This study shows that BDCM is both hepatotoxic and
      nephrotoxic to female rats after repeated dosing, but is only weakly hepatotoxic
      to female mice at the administered doses. Also, reduced activities of hepatic
      cytochrome P450 were observed in rats, but not mice. These species differences in
      toxicity and xenobiotic metabolizing enzyme inhibition caused by BDCM suggest
      that an understanding of the mechanism of toxicity of this compound will be
      critical when extrapolating rodent toxicity data to humans for this environmental
      pollutant.

PMID- 7801328
TI  - Adrenal activation of carbon tetrachloride: role of microsomal P450 isozymes.
AB  - Previous investigations demonstrated that carbon tetrachloride (CCl4) was
      activated by adrenal microsomes, resulting in various functional changes and
      ultimately in necrosis of the zona reticularis of the gland. Experiments were
      done to identify the adrenal P450 isozyme(s) involved in the bioactivation of
      CCl4. Incubation of microsomes from the zona reticularis (ZR) of the guinea pig
      adrenal cortex with CCl4 plus NADPH caused initiation of lipid peroxidation,
      covalent binding of CCl4-derived radioactivity to protein, and degradation of
      cytochrome(s) P450. Preincubation of the microsomal preparations with inhibitory
      antibodies to P450(17 alpha) or P450C21 decreased the corresponding enzyme
      activities (17 alpha-hydroxylation and 21-hydroxylation), but did not affect the
      activation of CCl4. 1-Aminobenzotriazole (ABT), a suicide inhibitor of some P450
      isozymes, decreased the enzyme activities catalysed by an adrenal 52,000 Da (52
      kDa) isozyme, but had no effect on the function of P450(17 alpha) or P450C21.
      However, ABT completely inhibited the CCl4-induced LP and covalent binding in
      adrenal microsomes. The results indicate that adrenal CCl4 activation is
      catalysed by the 52 kDa P450 isozyme and not by the steroid hydroxylases.
      Localization of the 52 kDa isozyme to the ZR probably accounts for the selective
      necrosis of this region of the gland by CCl4.

PMID- 7801329
TI  - Thiabendazole (TBZ) nephrotoxicity and recovery in ICR adult mice.
AB  - The nephrotoxicity and recovery following administration of thiabendazole (TBZ)
      were investigated in ICR adult mice. A single oral administration of TBZ (500
      2000 mg/kg body wt.) caused a dose-dependent proximal tubular necrosis in the
      kidney and increase in serum urea nitrogen 24 h after dosing. These changes were
      marked in mice of high dose groups (1000 or 2000 mg TBZ/kg body wt.). The time
      course of changes on kidney of mice treated with 1000 or 2000 mg TBZ/kg body
      weight were examined at 1, 2, 3, 5, 7 or 10 days after dosing. Light microscopy
      showed necrosis of proximal convoluted tubules from 1 day after dosing. Tubular
      necrosis was extensive 2 or 3 days after dosing. Partial regeneration from
      tubular necrosis was seen 3 days after dosing, and substantial regeneration had
      occurred from 5 days after dosing. Thus, TBZ-induced renal injury was most severe
      at 2 or 3 days after dosing and was followed by regeneration. Electron microscopy
      showed swelling of mitochondria in the proximal tubular epithelium at 1 day after
      dosing. The pathological changes were correlated with the changes in urinalysis,
      serum urea nitrogen concentration and kidney weight.

PMID- 7801330
TI  - p-Dichlorobenzene-induced hepatotoxicity in mice depleted of glutathione by
      treatment with buthionine sulfoximine.
AB  - p-Dichlorobenzene (p-DCB) is widely used as a moth repellent and a space
      deodorant. In mice pretreated with DL-buthionine sulfoximine (BSO; 2 mmol/kg or
      higher doses, i.p.), an inhibitor of glutathione (GSH) synthesis, administration
      of p-DCB (100-400 mg/kg, p.o.) resulted in dose-dependent hepatotoxicity as
      judged by increased serum alanine aminotransferase (ALT) activities and liver
      calcium concentrations and by histological examination of the liver, p-DCB alone
      (up to 1200 mg/kg) resulted in no hepatotoxicity. Administration of GSH monoethyl
      ester, which is known as a useful means for increasing organ GSH levels,
      protected against the hepatotoxicity caused by p-DCB in combination with BSO.
      Treatment with inhibitors of hepatic cytochrome P-450-dependent monooxygenases,
      carbon disulfide, metyrapone and piperonyl butoxide also prevented the
      hepatotoxicity. These results suggest that p-DCB is activated by a cytochrome P
      450-dependent metabolic reaction and that the hepatotoxicity is caused by
      inadequate rates of detoxification of the resulting metabolite in mice depleted
      of hepatic GSH by BSO treatment. The liver injury was preceded by an extensive
      depletion of hepatic GSH but not accompanied by significant changes in hepatic
      contents of lipid peroxides and protein thiols.

PMID- 7801331
TI  - Nicotine- or epinephrine-induced uteroplacental vasoconstriction and fetal growth
      in the rat.
AB  - We examined the relationship between nicotine-induced vasoconstriction in
      pregnant rat dams and fetal growth during the third trimester of pregnancy.
      Pregnant rats were continuously treated between days 13 and 19 of gestation with
      either nicotine (9.6, 4.8 or 2.4 mg/kg/day), epinephrine (0.72 microgram/kg/day),
      or saline via continuous infusion from a subcutaneously implanted osmotic
      minipump. Placental weights in rats treated with high dose nicotine and dams'
      body weights were severely reduced. However, fetal weights were not affected.
      Blood flows in uterus and placenta were quantified by measurement of tissue
      content of 85Sr-labelled microspheres injected via a carotid artery catheter.
      Both nicotine and epinephrine caused a significant reduction (> 40%) in uterine
      and placental blood flow. We conclude that vasoconstriction alone as a result of
      nicotine or epinephrine administration during the last trimester of gestation
      does not necessarily reduce nutrient supply to the fetus and does not affect
      fetal growth in rats.

PMID- 7801332
TI  - Ketoconazole-induced hepatic phospholipidosis in the mouse and its association
      with de-N-acetyl ketoconazole.
AB  - Ketoconazole (KC), an orally effective systemic antifungal agent, has been
      associated with symptomatic hepatotoxicity with an incidence as low as 1 in 2000.
      Studies from this laboratory have shown that in the mouse ketoconazole elicit a
      biphasic effect on drug metabolism and induced phospholipidosis. The pathogenesis
      of the latter, however, has never been established. Studies in mice demonstrated
      that ketoconazole administration induced phospholipid accumulation in the liver
      in a dose and time dependent fashion; and de-N-acetyl ketoconazole (DAKC), a
      major hepatic metabolite of KC was associated with this biochemical change. A
      comparative biochemical study following equimolar (0.47 nmol/kg p.o. x 7 days)
      administration of these two compounds indicated that hepatic phospholipids were
      elevated to a greater extent by DAKC treatment than by KC. Hepatic profiles of
      KC, DAKC, and other metabolites at 2, 7.5 and 24 h following single and multiple
      dosing regimens with either KC or DAKC indicated that KC was readily metabolized
      to DAKC whereas, DAKC appeared to be recalcitrant to metabolism and accumulated
      in the liver. In contrast to the biphasic effects of KC on hepatic enzyme
      activity observed previously following the administration of KC (enzyme
      inhibition as well as induction), the biological effects of DAKC were consistent
      with only an enzyme inhibitory effect: liver microsomal protein was not elevated;
      cytochrome P-450 was depressed; and ethylmorphine N-demethylase and benzphetamine
      N-demethylase were inhibited. Consequently the induction of phospholipidosis and
      the inhibition of drug metabolism associated with ketoconazole treatment were
      attributed to DAKC, whereas the inductive properties of KC were ascribed to the
      unchanged drug. The dramatic difference in the biological effects of these two
      compounds was attributed to differences in the orientation of these agents in
      lipid membranes. These results offer an explanation for the previously observed
      apparent inhibitory effects of KC on enzyme activities (Whitehouse et al. (1990b)
      Hepatic effects of ketoconazole in the male Swiss Webster mouse: temporal changes
      in drug metabolic parameters. Can. J. Physiol. Pharmacol., 68, 1136-1142) and
      suggest that DAKC may be the chemical entity responsible for the induction of
      phospholipidosis following ketoconazole administration.

PMID- 7801333
TI  - Renal cell type specificity of cephalosporin-induced cytotoxicity in suspensions
      of isolated proximal tubular and distal tubular cells.
AB  - We have developed an in vitro model for investigation of nephron heterogeneity
      and cell type-specific patterns of renal injury. To further validate our model
      and to study biochemical mechanisms of cephalosporin-induced injury, cytotoxicity
      of three cephalosporins was studied in freshly isolated proximal tubular (PT) and
      distal tubular (DT) cells from rat kidney. The three cephalosporins
      [cephaloridine (CPH), cephalexin (CXN), cephalothin (CTN)] were chosen because
      they exhibit varying degrees of nephrotoxicity in vivo and contain different
      functional groups. CPH produced greater amounts of lactate dehydrogenase release
      from PT cells than either CXN or CTN, indicating greater toxicity of CPH, which
      agrees with in vivo observations. DT cells were not affected by any of the
      cephalosporins. Thus, the cephem ring is sufficient to produce PT cell injury but
      the presence of other functional groups modifies toxicity. SKF-525A and alpha
      tocopherol protected PT cells from both CPH and CTN, suggesting involvement of
      cytochrome P-450 metabolism and oxidative stress. Both PT and DT cells exhibited
      transport of CPH or CXN and transport of CPH into PT cells was inhibitable by
      probenecid, consistent with action of a specific carrier. Transport alone,
      therefore, cannot account for the cell type specificity pattern in vitro. Effects
      on intracellular glutathione status, malondaldehyde formation, and uncoupler
      stimulated respiration were also investigated, and these generally correlated
      with cell type specificity patterns but not always with degree of cytotoxicity.
      These results validate further the isolated PT and DT cells as in vitro models to
      study cell type-specific renal injury and show a role for oxidative stress,
      cytochrome P-450 bioactivation, and mitochondrial dysfunction in cephalosporin
      induced PT cell injury.

PMID- 7801334
TI  - Approaches to the treatment of scorpion envenoming.
AB  - A total of 3866 patients stung by Tityus serrulatus scorpion was admitted to
      Hospital Joao XXIII, in Belo Horizonte, Brazil, over a 16-year period (an average
      of 241 cases per year). Of these, 73% were adults and 27% were children aged less
      than 14 years. The moderate or benign cases were treated with symptomatic
      measures and/or i.v. antivenom, whereas 168 severely envenomed children were
      treated in the Intensive Care Unit. Lung oedema was unilateral in several cases,
      with the presence of air bronchograms and a peripheral distribution, suggesting
      that a noncardiogenic factor is also involved in the genesis of lung oedema. The
      treatment consisted of symptomatic measures, support of vital functions and i.v.
      antivenom. The mortality was 1% among children and 0.28% for the total number of
      patients.

PMID- 7801335
TI  - Scorpionism and serotherapy in Mexico.
AB  - In Mexico, scorpionism is an endemic public health problem. The exact number of
      human accidents is unknown, but partial statistics suggests numbers close to
      200,000 per year. The documented number of fatality cases is in the order of 310
      people per year. We currently use horse antiserum in patients who show a clear
      picture of intoxication. Our personal experience in treating 38,068 people, from
      which over 20,000 received serotherapy, shows that the antiserum is very
      effective, in that none of the patients died.

PMID- 7801336
TI  - The treatment of the scorpion envenoming syndrome: the Saudi experience with
      serotherapy.
AB  - A protocol for treatment of scorpion sting based mainly on antivenom therapy was
      applied nation-wide in Saudi Arabia. At least 5 x 1 ml ampoules of antivenom
      diluted in 20-50 ml saline were injected slowly i.v. in all patients confirmed to
      have scorpion stings or suspected stings with systemic manifestations. A list of
      drugs was specified to be used in adjunctive therapy, when required. Analysis of
      1033 cases at Al-Baha region, 791 cases at Al-Qassim region and more than 600
      cases from 12 central and specialist hospitals in the Central Province revealed
      impressive results. Except for a 12-year-old boy who was inadequately treated
      with antivenom and died from pulmonary oedema, haematemesis, severe neurotoxicity
      and circulatory failure, no other fatalities occurred. The incidence of pulmonary
      oedema, hypertension, hypotension, cardiac dysrhythmias and neurological symptoms
      requiring drug therapy following antivenom administration was very slight. The
      period of stay in the hospital was reduced; most patients were symptom-free
      within 1-2 days. The early reaction to antivenom administration was lower than
      expected, amounting to 6.6% and 1.7% among Al-Qassim and Al-Baha victims,
      respectively. The severity of the reaction in both groups was low, consisting
      mainly of skin rashes, urticaria, wheezing and bronchial secretion, but no
      anaphylaxis. About 13.8% of Al-Baha victims were previously treated with
      antivenom but only 1.7% of the patients showed positive skin tests. This might be
      due to the low protein content of the antivenom and the action of the venom in
      releasing massive amounts of catecholamines.

PMID- 7801337
TI  - The role of the intensivist in the treatment of the cardiovascular manifestations
      of scorpion envenomation.
AB  - The following report summarizes the role of the intensivist in the treatment of
      the cardiovascular manifestations of scorpion envenomation within the intensive
      care unit. It emphasizes the need for a clear understanding the mechanisms
      involved behind the manifestations of myocardial damage and the rational approach
      of aggressive treatment of the overstimulated autonomic nervous system. The
      report emphasizes the complexity of the clinical picture and the intensivist
      approach based on clinical and experimental evidence, with excellent results.

PMID- 7801338
TI  - Vasodilators: scorpion envenoming and the heart (an Indian experience).
AB  - Our aim was to assess clinically whether there was any benefit in adding a single
      dose of sublingual nifedipine (a slow calcium channel blocker) to prazosin in the
      management of the cardiovascular manifestations of envenoming by the Indian red
      scorpion (Mesobuthus tamulus). A total of 163 patients stung by this species was
      admitted to hospital at Mahad between January 1991 and October 1993.
      Cardiovascular abnormalities were hypertension (59), of whom 42 had bradycardia
      and 17 had tachycardia; pulmonary oedema (14), of whom eight had hypertension and
      six hypotension; supraventricular tachycardia (eight), of whom three had
      hypotension and one died. Of the remaining patients, 78 demonstrated severe
      excruciating local pain at the site of sting but had no systemic involvement.
      Nineteen patients with hypertension and tachycardia were given a single dose of
      sublingual nifedipine plus prazosin on admission, then prazosin alone repeated 6
      hourly. Five patients with massive life-threatening pulmonary oedema recovered
      after being given intravenous sodium nitroprusside. Prazosin alone helped to
      alleviate cardiovascular manifestations in the remaining 52 victims. One patient
      was admitted in a deep coma, 12 hr after the sting, and died. Eight victims whose
      blood pressure had been controlled in hospital by nifedipine plus prazosin
      developed acute pulmonary oedema necessitating additional doses of prazosin for
      recovery. Fifty-two victims treated with prazosin alone did not develop pulmonary
      oedema and the drug appeared to hasten the recovery. In the presence of high
      blood pressure, tachycardia, a murmur and impending myocardial failure,
      nifedipine appeared to contribute to cardiopulmonary instability and to augment
      myocardial oxygen consumption. In this situation calcium channel blockers should
      probably be avoided.

PMID- 7801339
TI  - Scorpion envenoming and the role of insulin.
AB  - Scorpion envenoming results in a severe autonomic storm with a massive release of
      catecholamines, increased angiotensin II and inhibition of insulin secretion.
      These hormonal alterations could be responsible for the pathogenesis of a variety
      of clinical manifestations. Under these conditions, scorpion envenoming
      essentially results in a syndrome of fuel-energy deficits and an inability to
      utilize the existing metabolic substrates by vital organs causing multi-organ
      system failure and death. Based on our animal experiments in which insulin
      administration reversed the metabolic and ECG changes induced by scorpion
      envenoming and treating the poisonous scorpion sting victims with insulin, we
      consider that insulin has a primary metabolic role in preventing and reversing
      the cardiovascular, haemodynamic, and neurological manifestations and pulmonary
      oedema induced by scorpion envenoming. The use of continuous infusion of regular
      crystalline insulin at the rate of 0.3 U/g glucose and glucose at the rate of 0.1
      g/kg/hr, with supplementation of potassium as needed and maintenance of fluid
      electrolytes and acid-based balance, has become a routine protocol in our setting
      for treating the victims of scorpion envenoming.

PMID- 7801341
TI  - The cytotoxicity of macrocyclic trichothecenes, roridin A and verrucarin A, on
      murine T-cells is reduced by Ia-negative splenic adherent cells.
AB  - The in vitro effect of macrocyclic trichothecenes, roridin A and verrucarin A,
      and a non-macrocyclic trichothecene, T-2 toxin, on the concanavalin A-induced
      murine T-cell blastogenesis was investigated. The macrocyclic trichothecenes
      inhibited the blastogenesis of both thymocytes and splenocytes, splenocytes being
      more resistant than thymocytes. Such resistance to macrocyclic trichothecenes was
      not observed in splenic T-cells separated from the other cell population, nor in
      splenocytes depleted of adherent cells. In order to find the cell population
      responsible for resistance, the toxins were incubated with fractionated splenic
      cells and then cytotoxicity of the supernatants of the incubation mixtures was
      examined by using T-cell blastogenesis assay. The results showed that the
      splenocytes depleted of Ia-negative cells had the ability to reduce the
      cytotoxicity of the macrocyclic trichothecenes, but not that of T-2.

PMID- 7801340
TI  - Reliability of the simple 20 minute whole blood clotting test (WBCT20) as an
      indicator of low plasma fibrinogen concentration in patients envenomed by
      Bothrops snakes. Butantan Institute Antivenom Study Group.
AB  - Reliability of the simple 20 minute whole blood clotting test (WBCT20) as an
      indicator of low plasma fibrinogen concentration in patients envenomed by
      Bothrops snakes. Toxicon 32, 1045-1050, 1994.--A simple whole blood clotting test
      (WBCT20) was assessed for its efficacy in determination of severe
      defibrinogenation in patients envenomed by Bothrops snakes in Brazil. There was a
      close relationship between the results of the WBCT20 and plasma fibrinogen levels
      in 69 moderately envenomed patients. The advantage of the WBCT20 over estimation
      of plasma fibrinogen concentrations in patients is that it is a simpler, faster
      and more reliable test. It is also of use in assessing the effectiveness of
      antivenom therapy in relation to the restoration of blood coagulability.

PMID- 7801342
TI  - Anemonefish symbiosis: vulnerability and resistance of fish to the toxin of the
      sea anemone.
AB  - Protein toxins (20 kD molecular mass) causing lysis of human erythrocytes were
      isolated from sea anemones (Heteractis magnifica, Madang, Papua New Guinea, and
      Entacmaea quadricolor, Red Sea), which host anemonefish (Amphiprion sp.). These
      toxins are also ichthyotoxic. Freshwater and marine fish exposed to toxin
      concentrations of 0.5 micrograms/ml water were killed within 2 hr and exhibited
      extensive pathological alterations of the gill filaments. Amphiprion species,
      e.g. clarkii and percula, which live in the sea anemones Heteractis crispa and
      Stichodactyla mertensii, were highly vulnerable to the Heteractis magnifica
      toxin, whereas A. percula from the sea anemone H. magnifica proved to be toxin
      resistant. However, another species, A. perideraion also living in H. magnifica,
      was highly sensitive to the toxin. The two toxins exhibited cross-reactivity:
      Amphiprion, resistant to H. magnifica toxin, was also resistant to Entacmaea
      quadricolor toxin; but all fish were killed by other membrane-active substances
      such as gramicidin, saponin and latrunculin. The results of the study indicate
      that resistance to toxins secreted by the sea anemone has evolved in some
      Amphiprion species, but it is not an essential or a major factor in the
      anemonefish symbiosis. The skin's mucus layer seems to provide protection from
      nematocyst discharge.

PMID- 7801343
TI  - Purification of an acidic phospholipase A2 from Bothrops lanceolatus (fer de
      lance) venom: molecular and enzymatic properties.
AB  - The acidic phospholipase A2 from Bothrops lanceolatus venom has been purified by
      gel filtration on Sephadex G-50 and ion exchange chromatography on CM-cellulose.
      Analysis by FPLC on Mono-Q column of the purified phospholipase A2 indicated that
      it is a mixture of several isoenzymes. The two major isoforms consist of a single
      polypeptide chain with mol. wts of 14,500 and 15,000, which slightly differ in
      their isoelectric point (4.9 and 5.3) and amino acid composition. However,
      enzymatic and pharmacological properties of the various isoenzymes are identical.
      The phospholipase from B. lanceolatus venom is characterized by a progressive
      increase in the rate of hydrolysis when enzymatic activity is determined with
      crude egg yolk as substrate in the absence of detergent. This phenomenon, which
      is not observed with mixed micelles of lecithin-detergent, is not due to the
      presence of a phospholipase A2 inhibitor in the venom, as previously suggested by
      several investigators in the case of other Bothrops and Cobra venoms. It is
      rather a catalytic characteristics of B. lanceolatus venom phospholipase, the
      enzymatic activity of which depends on the physical state of phospholipids.
      Bothrops lanceolatus acidic phospholipase A2 is non-toxic.

PMID- 7801344
TI  - Primary structures of two proteins from the venom of the Mexican red knee
      tarantula (Brachypelma smithii).
AB  - Venom of the Mexican red knee tarantula (Brachypelma smithii) was fractionated by
      gel filtration over Sephadex G-50 Fine. Small polypeptides present in the second
      and third peaks were subfractionated by cation exchange and reversed-phase FPLC.
      One major, basic protein was isolated and sequenced from each G-50 fraction using
      a gas-phase protein sequencer. Primary structures were completed and confirmed
      using tandem mass spectrometry and carboxypeptidase digestions. Protein 1
      contains 39 residues, including six cysteine residues in three disulfide bonds.
      It is identical to one of the isoforms of ESTX from the venom of the tarantula
      Eurypelma californicum. Brachypelma smithii Protein 5 contains 34 residues,
      including six cysteine residues in three disulfide bonds. Disulfide bond
      assignments for both proteins are provided. Protein 5 shows most similarity with
      toxin Tx2-9 from the Brazilian 'armed' spider, but only displays 41% sequence
      identity. Similarities with other proteins are lower. Proteins 1 and 5 appear
      unrelated to each other.

PMID- 7801345
TI  - Quaternary structure of botulinum and tetanus neurotoxins as probed by chemical
      cross-linking and native gel electrophoresis.
AB  - Botulinum and tetanus neurotoxins are water-soluble proteins (mol. wt 150,000)
      produced by Clostridium botulinum and Clostridium tetani, respectively. It is
      believed that these neurotoxins, once internalized via receptor-mediated
      endocytosis, form membrane channels in order to traverse the endosomal membrane
      and enter the cytoplasm of the nerve terminal. Investigation of the associative
      properties between neurotoxin molecules could yield an understanding of this
      channel formation. That is, an association between neurotoxin monomers could
      result in an oligomeric form of the neurotoxin necessary for assembly of a
      channel through the hydrophobic interior of the endosomal membrane, thereby
      allowing passage of the neurotoxin or its active fragment through the resulting
      pore. Based on the native gel electrophoresis and chemical cross-linking
      experiments, tetanus neurotoxin exists as a dimer and a trimer, type A botulinum
      neurotoxin exists as a dimer, trimer, and a larger species, type E botulinum
      neurotoxin exists as a monomer and dimer, and type B botulinum neurotoxin appears
      to exist as a dimer in aqueous solution. The results imply that quaternary
      structures of these neurotoxins may play an important role in their mode of
      action during neuronal poisoning.

PMID- 7801346
TI  - Biological activities of [Thr2]sarafotoxin-b, a synthetic analogue of sarafotoxin
      b.
AB  - The 21 amino acid sarafotoxins (SRTX) c and d/e as well as endothelin-3 (ET-3)
      are known to be less toxic and weaker pharmacologically than the other
      isopeptides SRTX-a, SRTX-b and ET-1. Since SRTX-c, SRTX-d/e and ET-3 possess a
      Thr instead of a Ser at position 2, we investigated the possibility that this
      mutation could be responsible for the observed biological differences. Here we
      show that the synthetic [Thr2]SRTX-b has indeed a lower vasoconstriction efficacy
      (approximately 35%) in the rabbit aorta, but it is nearly as potent as SRTX-b in
      toxicity tests and in influencing contraction of the rat uterus. Using monoclonal
      antibodies directed against the structurally related endothelin-1, we also show
      that the antigenicity of the analogue is comparable to that of SRTX-b, suggesting
      that the overall structure of the two peptides is similar, despite the
      substitution at position 2. We suggest that the Thr2 substitution contributes to
      the lower activity of the 'weak' peptides in some systems; however, additional
      substitutions found in the 'weak' peptides of the ET/SRTX family most probably
      contribute to their low pharmacological activity.

PMID- 7801347
TI  - Hematopoietic alterations after exposure to T-2 mycotoxin.
AB  - Adult mice were exposed by oral gavage to 0.75, 1.25, or 1.75 mg/kg body weight T
      2 mycotoxin for 5 consecutive days. Thymic atrophy on the 2nd day following
      cessation of dosing was profound, and was characterized by significant decreases
      in the total number of cells within all phenotypes defined by CD4 and CD8 cell
      surface antigen expression. Further, the distribution of thymocytes within these
      phenotypes was significantly altered. Increased percentages of CD4-8- (DN) and
      decreased percentages of CD4+8+ (DP) cells in thymuses from treated animals
      suggested that T-2 toxin may inhibit thymocyte maturation. In addition to thymus,
      the bone marrow of treated animals showed a highly significant hypocellularity,
      indicating that this hematopoietic compartment may also be targeted by T-2 toxin.
      A trend toward reduced splenic cellularity was additionally observed in exposed
      animals, but failed to reach significance. A significant decrease in the total
      number of both B and T-lymphocytes present within the spleen was observed,
      however. These data, taken together, indicate that effects at multiple
      hematopoietic compartments involved in the production of T-lymphocytes may
      contribute to the peripheral T-cell lymphocytopenia and T-cell mediated
      immunosuppression produced by T-2 toxin.

PMID- 7801348
TI  - Biochemical and morphological changes in rat muscle cultures caused by 28,000
      mol. wt toxin of Bacillus thuringiensis israelensis.
AB  - The 28,000 mol. wt protein of Bacillus thuringiensis israelensis showed a high
      degree of toxicity to rat muscle in culture. Application of 1 microgram/ml to the
      culture medium completely inhibited cell fusion. Reversibility of this effect was
      demonstrated by replacement of the culture medium with fresh medium, and the
      consequence was that cell fusion was resumed. When differentiated myotubes were
      treated with 1 microgram/ml of the toxin, the spontaneous contractile activity
      was abolished within 20 min. Cytotoxic effects were observed 1 hr after treatment
      was initiated, as manifested by creatine kinase (CK) release to the medium. Two
      hours after toxin was applied to the muscle culture, the myotubes were
      deteriorated whereas the mononucleated cells were not affected. Six or 7-day-old
      cultures which were treated by 1 microgram/ml of 28,00 mol. wt toxin revealed a
      change in the levels of Na+ and K+ within the fibres as analysed by X-ray
      microanalysis (XRMA). Preincubation of the toxin for 20 min with phospholipids
      before application to the cells reduced the cytotoxic effect.
      Phosphatidylinositol and phosphatidylserine were the most efficient inhibitors,
      whereas phosphatidylcholine, sphingomyelin and phosphatidylethanolamine were less
      effective in protecting cultures from the cytotoxic effects of the 28,000 mol. wt
      protein.

PMID- 7801349
TI  - Clostridium butyricum neurotoxin: partial amino acid sequence of major
      proteolytic fragments and intracellular activity in PC12 cells.
AB  - The approximately 150 kDa single-chain neurotoxin produced by Clostridium
      butyricum, reported to be similar to C. botulinum neurotoxin serotype E (Gimenez
      and Sugiyama, Infect. Immun. 54, 926-929, 1988), was probed with trypsin and
      endoproteinase Lys-C. The two proteases cleaved the butyricum neurotoxin between
      residues Arg 421-Lys 422 and Lys 418-Gly 419, respectively. Cleavage at this
      region, highly susceptible to proteolysis, generated approximately 50 kDa light
      and approximately 100 kDa heavy chains, whose identities were established by
      amino acid sequence determination. In the approximately 150 kDa dichain
      neurotoxin these two chains remained linked by an interchain disulfide bond. The
      endoproteinase Lys-C also cleaved the heavy chain between residues Lys 594-Ile
      595, yielding a approximately 73 kDa fragment. A total of 77 amino acid residues
      was identified by Edman degradation of the major fragments generated by
      proteolysis. By analogy with other botulinum neurotoxin serotypes, the light
      chain contains the intracellular inhibitory domain and the heavy chain the
      receptor-binding and channel-forming domains. Butyricum neurotoxin, whether in
      single-chain or dichain form, inhibited approximately 70% of the Ca2+ stimulated
      [3H]norepinephrine release from permeabilized PC12 cells. Reduction with 5 mM
      dithiothreitol enhanced the intracellular inhibitory activity of dichain
      neurotoxin about 30-fold and increased the extent of inhibition to about 80%,
      while the activity of single-chain neurotoxin was slightly affected. Increase in
      the intracellular inhibitory activity of butyricum neurotoxin following mild
      treatment with trypsin (i.e. conversion of the single-chain protein to the
      dichain form) was virtually complete within 6 min.

PMID- 7801350
TI  - Structure-activity relationships and interactions among trichothecene mycotoxins
      as assessed by yeast bioassay.
AB  - A yeast (Kluyveromyces marxianus) bioassay was used to establish the relative
      toxicity of 16 trichothecenes and some of their interactions. Removal of an
      isovaleryl group, one or two acetyl groups, or two acetyl plus an isovaleryl
      groups from T-2 toxin (T2) to form diacetoxyscirpenol, HT-2 toxin (HT2), T2-triol
      and T-2 tetraol (T2-4ol) decreased toxicity 7, 36, 276 and 558-fold,
      respectively. A combination of T2 and HT2, T2 and T2-4ol, deoxynivalenol (DON)
      and nivalenol (NIV), or DON and T2 exhibited synergistic (T2 and HT2 or DON and
      NIV) or antagonistic (DON and T2) responses.

PMID- 7801352
TI  - Bibliography of toxinology.

PMID- 7801351
TI  - Relationship between the binding sites for an alpha-conotoxin and snake venom
      neurotoxins in the nicotinic acetylcholine receptor from Torpedo californica.
AB  - Photoinduced cross-links between the iodinated Lys26-p-azidobenzoyl derivative of
      neurotoxin II from Naja naja oxiana cobra venom and nicotinic acetylcholine
      receptor from Torpedo californica (AChR) have been studied in the presence of
      alpha-conotoxin GI from the marine snail C. geographus. Preincubation of the AChR
      enriched membranes with increasing concentrations of alpha-conotoxin GI protects
      first the gamma subunit from photolabelling and then the delta subunit, the IC50
      values being 0.76 and 5.01 microM, respectively. The results obtained, in view of
      the relevant data in literature, demonstrate that the (alpha + gamma) site, which
      is the high affinity site for d-tubocurarine, has also a higher affinity for an
      alpha-conotoxin than the (alpha + delta) containing site. The latter has a
      somewhat higher affinity than the (alpha + gamma) site towards some naturally
      occurring snake venom alpha-neurotoxins or their derivatives.

PMID- 7801353
TI  - Sustaining health care in poor countries.

PMID- 7801354
TI  - Using lot quality assessment techniques to evaluate quality of data in a
      community-based health information system.
AB  - We report here on the application of lot quality assessment (LQA) techniques by
      managers of a Save the Children (SC) Child Survival Project in Mbalachanda,
      Malawi, to evaluate data contained in a community-based health information
      system. By defining 'lots' as the health records for all households with children
      under 5 years old which were listed on the rosters of village health promoters
      supervised by a given community health supervisor, and by establishing criteria
      for 'acceptability' of samples drawn from these lots, we were able to identify
      and offer additional supervision to health workers (supervisors as well as
      village health promoters) who were not performing adequately. As LQA sampling
      procedures require that only a small sample be drawn from each lot, the
      assessment could be conducted easily and quickly. Health workers were found to
      have the greatest need for help in updating demographic data and information
      about home-based oral rehydration therapy (ORT) training sessions, and the least
      for help in recording children's immunization status. We conclude that LQA can be
      a useful supervisory tool for health programme managers.

PMID- 7801355
TI  - The patient as a starting point for health education in leprosy control.
AB  - The current strategy for leprosy control remains the early diagnosis and
      effective treatment of leprosy patients with multi-drug therapy (MDT), together
      with the prevention and/or limitation of disabilities. This paper proposes
      patients-centred health education strategies that may help in the goal of
      eliminating leprosy as a public health problem by the year 2000, in leprosy
      endemic countries like Nigeria.

PMID- 7801356
TI  - The diurnal variation of stroke in Ghana.
AB  - In 68 patients presenting with stroke in Ghana a significant (P < 0.001) peak in
      onsets occurred between 0600 h and 1000 h. There were no significant differences
      in time of onset between men and women or hypertensive and non-hypertensive
      patients. Reasons for the peak of onsets are discussed. A similar diurnal pattern
      of stroke has been described in temperate countries: any benefits such as timing
      of prophylactic measures that ensue from research on stroke in temperate climates
      are likely to be of benefit if also applied to those at risk of stroke in a
      tropical climate.

PMID- 7801357
TI  - The importance of early erythematous reaction in purified protein derivative skin
      testing.
AB  - We attempted to assess the diagnostic value of the early erythematous reaction
      observed at the sixth hour after the application of purified protein derivative
      (PPD) skin testing. For this purpose, 64 children with pulmonary tuberculosis and
      49 healthy age-matched controls were PPD skin tested. Our results showed that the
      erythematous reaction of 5 mm or greater at the sixth hour was able to detect
      patients with active tuberculosis with 76% sensitivity, 85% specificity, 87%
      positive predictivity and 73% negative predictivity. Among 113 subjects, 6 h
      erythematous reaction of 5 mm or greater in size had 83% sensitivity to detect
      the ones who subsequently developed 10 mm or greater induration reaction at 48 h.
      We concluded that the sixth hour early erythematous reaction is just as helpful
      as the 48 h induration of 10 mm or greater in detecting patients with pulmonary
      tuberculosis.

PMID- 7801358
TI  - Detection of Helicobacter pylori in endoscopic biopsies in Sudan.
AB  - We studied the prevalence of Helicobacter pylori in Sudanese subjects with
      gastroduodenal inflammation. H. pylori was looked for in biopsy specimens taken
      from the antrum by two methods: rapid urease test [Campylobacter-like organism
      (CLO) test] and culture using Skirrow's selective supplement. One hundred
      subjects were studied. H. pylori was found in 80% of patients with gastritis, 56%
      of patients with duodenal ulcer, 60% of patients with duodenitis and 16% of
      normal control subjects. It was neither detected in patients with gastric ulcer,
      nor in patients with oesophagitis or in those with oesophageal varices due to
      schistosomiasis, when using culture. However, it was found in 50% of patients
      with oesophagitis, when using CLO test.

PMID- 7801359
TI  - Utility of arm circumference as a screening instrument to identify women at
      nutritional risk.
AB  - Anthropometric measurements of 567 healthy nonpregnant women aged 20-40 years
      were studied to assess the utility of mid-upper-arm-circumference as a screening
      test to detect malnutrition. The prevalence of malnutrition in the study sample
      was 38.4%. A cut-off point of 24 cm was found to be most appropriate in the study
      setting as at that level the sensitivity, specificity and positive predictive
      values were 71.1%, 69.6% and 59.4%, respectively.

PMID- 7801360
TI  - Evaluation of proptosis in paediatric patients in Africa.

PMID- 7801361
TI  - Basidiobolomycosis in Ghanaian children.

PMID- 7801362
TI  - Tuberculous mastitis.

PMID- 7801363
TI  - A man with no penis.

PMID- 7801364
TI  - Acute tuberculous pancreatitis associated with HIV infection.

PMID- 7801365
TI  - Hydatid cyst of the breast.

PMID- 7801366
TI  - Solitary lumbar neurofibroma in a patient with neurofibromatosis.

PMID- 7801367
TI  - Entero uterine fistula.

PMID- 7801368
TI  - Tuberculous pyelocutaneous fistula.

PMID- 7801369
TI  - Ectopic pregnancies.

PMID- 7801370
TI  - Tracheobronchial foreign bodies: removal without a bronchoscope.

PMID- 7801371
TI  - An easy screening test for tubal infertility.

PMID- 7801372
TI  - External carotid artery control in the surgical treatment of advanced malignant
      scalp and facial tumours in Zaria, Nigeria: report of seven cases.

PMID- 7801373
TI  - Prevalence of parental medication on children before going to the hospital.

PMID- 7801375
TI  - An easily made obstetrical vacuum extractor.

PMID- 7801376
TI  - Malignant hyperthermia treated without dantrolene.

PMID- 7801374
TI  - Ornidazole and secnidazole in the treatment of symptomatic intestinal amoebiasis
      in childhood.

PMID- 7801377
TI  - The baby friendly hospital initiative: involvement of health personnel.

PMID- 7801379
TI  - Infective abortion--does it exist and is it connected with AIDS?

PMID- 7801378
TI  - Pattern of surgical disorders of the breast in Zambia.

PMID- 7801380
TI  - Resistance pattern of Pseudomonas aeruginosa occurring in northern part of
      Bangladesh.

PMID- 7801381
TI  - A practical method to reduce HIV risk in African women.

PMID- 7801382
TI  - Diabetes.

PMID- 7801383
TI  - The pattern of pyomyositis in Zaria.

PMID- 7801384
TI  - [The immunocytopoietic signs of circulating human lymphocytes in pathological
      states].
AB  - The dynamics of associative, size, and immediate rosette classes of circulating
      lymphocytes was studied in donors and patients with different pathogenesis of
      migration of activated lymphocytes. On the basis of the associated dynamics of
      lymphocyte classes in blood and pleural exudation as well as the correlation
      analysis two functional groups of lymphocytes were distinguished: a group of
      early proliferative activated lymphocytes and a group of temporarily intact
      lymphocytes circulating for a long time.

PMID- 7801385
TI  - [Repeatability and heredity in assessing the genotype of breeding bulls].
AB  - Phenotypic correlations between the breeding value of bulls and the level of
      lactation of their mothers as well as the results of the assessment of their
      fathers were calculated on the basis of the data of tests and assessments of 1687
      diary bulls for quality of their progeny. A relatively weak correlation was
      detected for the paternal side of the pedigree. This was due to a low efficiency
      of genotype assessments. A functional relationship between the repetition value
      and the number of daughters and the number of herds, in which they were used, was
      determined.

PMID- 7801386
TI  - [A method for assessing the genotype of sire bulls].

PMID- 7801387
TI  - [Dermatoglyphics and cancerous diseases].
AB  - The dermatoglyphic analysis of finger and palm prints was conducted in oncologic
      patients living in the same town and in corresponding with respect to the number
      control groups of inhabitants of the same town that were matched to each patient
      by the most relevant risk factors. The study was based on 61 dermatoglyphic
      characters. Using computer pattern recognition programs sufficiently informative
      subcomplexes of these characters were formed. They permitted to discriminate
      between ill and control persons.

PMID- 7801388
TI  - [Screening for deletion in patients with Duchenne's myodystrophy by multiplex
      amplification].
AB  - Patients with Duchenne muscular dystrophy were analyzed using the method of
      polymerase chain reaction in order to reveal deletions in the dystrophin gene.
      Deletions of different lengths and locations were detected in 28 of 78 ill boys.
      The highest number of deletions was detected in the 3'-end of the gene (the 45
      50th exons).

PMID- 7801389
TI  - [Diagnostic imaging over 100 years--and after the year 2000].

PMID- 7801390
TI  - [Low-energy laser therapy in medial tibial stress syndrome].
AB  - The effect of low-energy laser therapy on shin splints was examined in a
      randomized study with an unblinded design. Constripts from the Jutland Dragoon
      regiment with shin splints were given either active laser treatment (40 mW in 60
      sec per cm tender tibia edge) or placebo laser. All patients were exempted from
      normal duty concerning activities like running and march. Forty-nine patients
      participated in the study, 23 in the laser group and 26 in the control group.
      From the start the study was designed to be double-blind, but by accident the
      code was broken towards the end of the study. We found no significant differences
      between the groups regarding pain visual analog score and readiness to return to
      active duty after 14 days.

PMID- 7801391
TI  - [Use of analyses in acute myocardial infarction evaluated by quality assurance
      methods].

PMID- 7801392
TI  - [Risks and adverse effects of acupuncture therapy].
AB  - Forty published articles about acupuncture and related side-effects are reviewed.
      Several serious complications are described among the mentioned side-effects,
      e.g. pneumothorax, bacterial endocarditis, hepatitis and spinal lesion.
      Contraindications for the use of acupuncture are discussed.

PMID- 7801393
TI  - [Intravascular ultrasound].
AB  - Intravascular ultrasound (IVUS) is a new imaging modality for the study of
      cardiovascular disease, which enables us to visualize the structure of the wall
      and the inner surface of the vessel. The instrument consists of a small very high
      frequency ultrasound transducer (12.5-40 MHz) mounted on the tip of a catheter,
      which can be introduced into the vessel. By rotating either the transducer itself
      or a mirror situated proximal to the transducer, cross-sectional images of the
      vessel wall with a high resolution are obtained. IVUS can distinguish between the
      different layers of the vessel and between different kinds of atherosclerotic
      plaques. Furthermore, the changes created by various interventional procedures
      may be visualised. These qualities of IVUS begin to comply with the rising
      demands for a better assessment of the results of the interventions--demands that
      cannot be fulfilled by arteriography. Moreover, IVUS may contribute to vascular
      diagnostics without the use of x-ray and contrast media, but is limited by its
      invasive nature and, until now, high costs.

PMID- 7801394
TI  - [Methods for measurement of wound extent].
AB  - Healing is a biologically complicated process, which is difficult to measure
      objectively. Several products and pharmaceuticals have been applied to the
      treatment of both acute and chronic wounds. There are, however, only few well
      documented studies of the effect and many recommendations are based on
      casuistries, undocumented studies or in vitro studies. One of the most prominent
      problems has been the lack of exact measurements. This article describes the
      available clinical measurement parameters and discusses their strengths and
      weaknesses. The following methods of measurement are described: Wound surface
      area (WSA), wound area (WA), and volume (VOL). A stratification of wounds before
      measuring is suggested depending on aetiology and form (volume or surface
      wounds). The most sensitive measure for assessment of wound healing is
      recommended. From a clinical point of view the transition from a volume to
      surface wound is not distinct, and therefore WA is recommended as the most
      relevant measurement during wound healing.

PMID- 7801395
TI  - [Popliteal artery entrapment syndrome].
AB  - Popliteal artery entrapment syndrome (PAES) should be suspected in young persons
      without predisposing factors to arteriosclerosis, who present with unilateral
      claudication in the calf and foot. This entity results from a developmental
      abnormal relation between the popliteal artery and the medial head of the
      gastrocnemius muscle. PAES is mostly found in young sportsmen or young soldiers
      with well-developed muscles. The onset of the symptoms is often sudden, occurring
      during an episode of intense lower extremity activity. The diagnosis is best
      established by a thorough clinical examination combined with functional tests
      followed by a CT-scan and/or biplanar arteriography. The treatment is surgical
      with decompression of the popliteal artery and in cases of arterial thrombosis
      also interposition of an autologous graft. Prophylactic decompression should be
      considered in asymptomatic cases.

PMID- 7801396
TI  - [Complications and late sequelae after nasotracheal intubation].
AB  - A total of 379 patients admitted to the Intensive Care Unit (ICU) for mechanical
      ventilation were prospectively investigated for lesions of the nose, nasal
      cavity, ears and larynx during and after nasotracheal intubation. One to two
      years later, the surviving patients were questioned to investigate late
      persisting sequelae. During intubation and up to five days following extubation,
      inflammatory changes and ulceration of the nostrils or nasal septum were found in
      respectively 76 (20%) and 110 (29%) patients. There were bleedings from the nasal
      cavity in 67 (19%) and fractures of the conchae in 40 patients (11%). Hoarseness
      was noted in 135 patients (42%). Inflammatory changes and ulcerations of the
      nostril and nasal septum were correlated to the duration of intubation. Among the
      281 patients included in the follow-up study, 100 (35%) had symptoms from the
      nose and nasal cavity. Sixty-five (24%) had symptoms related to the ears, 56
      (20%) to the maxillary sinus, 81 (29%) to the voice and 90 (32%) to the throat.
      Increasing duration of intubation was found to be correlated to persisting
      symptoms from the larynx. Former ulcerations of the nose were associated with a
      tendency toward nasal bleeding. To avoid as many complications as possible from
      the nose and nasal cavity, we recommend orotracheal intubation. As late sequelae
      from the larynx increase with the duration of intubation, perhaps tracheostomy
      should be performed earlier than is general practice today, but that has to be
      proven in forthcoming studies.

PMID- 7801397
TI  - [10-year survival after lung resection for lung cancer].
AB  - The purpose of the study was to investigate the prognosis for patients treated
      for lung cancer by operative resection in the Copenhagen area. Ninety-four
      consecutively operated patients were followed prospectively for ten years.
      Seventy-one percent of the patients had been operated radically. The five- and
      ten-year survival for this group was respectively 46 and 27%. All non-radically
      operated patients were dead after four years. The postoperative mortality and
      long-term survival correspond to international results. Type of cancer and mode
      of operation did not affect survival in the radically operated patients.

PMID- 7801398
TI  - [Evaluation of patients with below knee amputation with respect to postoperative
      prosthesis fitting].
AB  - A follow-up of 78 patients who underwent amputations just below the knee at
      Herlev University Hospital in the county of Copenhagen during the period 1985-88
      is reported. The examination was carried out at an average of 39 months later.
      There was a high early mortality postoperatively as well as in the subsequent
      years. Of the survivors, about 87% were found to be candidates for prosthetic
      fitting. Nearly all of these patients became functional ambulators. The long-term
      survival rate was primarily correlated to a reduced occurrence of concurrent
      medical diseases, especially of cardiovascular nature. All women with diabetes
      mellitus were deceased at the time of examination. This is a well-known
      phenomenon, relating diabetes with a six times higher mortality risk. The study
      indicates that the effort and expense of fitting and training patients with
      prostheses may be well worthwhile.

PMID- 7801399
TI  - [Agricultural injuries in Ringkjobing County].
AB  - The aim of the study was to investigate agricultural injuries in Ringkjobing
      County in the period 1.1-31.12.1992. At the five local hospitals, all persons
      treated after accidents on farms were registered prospectively and classified
      according to activity and injury severity (AIS-90). A total of 294 injured
      persons were registered. Of those, 257 (87%) accidents were due to working
      activities. Four persons (1%) were killed in the accident. The mean age was 42
      years (2-81). Fractures were seen in 32% of the patients and open wounds in 21%.
      Only 6% had lesions with an AIS-score > 2, and only six patients (2%) had lesions
      with an AIS-score > 3. In spite of that, 30% were unable to work for more than
      four weeks because of the injury. An injury prevention programme towards
      agricultural injuries is therefore suggested.

PMID- 7801400
TI  - [The appointed guardian--a counsellor of the forensic psychiatric patient?].
AB  - Forensic psychiatric patients who are submitted to a special measure, are
      according to the new mental health act allowed to complain of certain coercive
      measures. In contrast to other psychiatric patients forensic patients are not
      allotted a patient counsellor. Instead these patients must use an appointed
      guardian if they need assistance in complaining. The forensic files of 51
      patients have been reviewed with a focus on the presence of appointed guardians
      and previous remand prison. In spite of the requirements of the penal code, only
      two-thirds of the patients had an appointed guardian on the day of registration.
      Only one third of the patients were allotted an appointed guardian in connection
      with pronouncement of sentence. More extensive investigations of this problem
      would be desirable. As the appointed guardian and the patient counsellor are not
      identically qualified, the forensic psychiatric patient receives inferior
      assistance if he wishes to complain. The new section in the penal code dealing
      with appointed guardians will to some extent change this state of things.

PMID- 7801401
TI  - [The social recruitment of medical students at Copenhagen University 1992/1993].
AB  - As part of a prospective survey of medical students' conditions and of the
      different kinds of influence they are subjected to during their study periods, we
      looked into the question of from which social strata the students were recruited.
      Two hundred and fifty-four (79%) of 323 medical students matriculated during the
      summer of 1992 answered a structured questionnaire forwarded to them. One hundred
      and thirty-one (52%) medical students were recruited from the highest social
      class (I), whereas only 19 (7%) were recruited from the lowest social class (V).
      In comparison, the underlying population in the age groups relevant for the
      survey is made up as follows: 7% in social class I and 20% in social class V. A
      comparison with earlier surveys shows that only insignificant changes in the
      medical students' social class profiles have taken place in spite of the
      introduction of better possibilities of financing medical studies irrespective of
      social class affiliations.

PMID- 7801402
TI  - [Suspected tumor in undiagnosed bronchial foreign body].
AB  - A case of long term retention of a bronchial foreign body in a 62-year old female
      patient is presented, which mimicked lung carcinoma. Despite a negative history
      of choking, the diagnosis airway foreign body should be kept in mind.

PMID- 7801403
TI  - [A complication of oleothorax--after 38 years].
AB  - We present a case-history of a 50 year-old woman who 38 years earlier had been
      operated for pulmonary tuberculosis by plugging of the pleural cavity with oil
      (oleothorax). She developed a tumour under the scapula, which it turned out was
      due to migration of the oil plug to the subscapular area, an unusual complication
      to oleothorax. Other complications are described.

PMID- 7801404
TI  - [Cheese-packers and specific precipitating antibodies].

PMID- 7801405
TI  - [Treatment of ascites].

PMID- 7801406
TI  - [Prospective validation of PMN-elastase as a prognostic parameter in the surgical
      intensive care unit].
AB  - The study presented investigates prospectively the clinical value of the PMN
      elastase as a sequel parameter in 954 patients of a surgical intensive care unit.
      The elastase-values measured discriminate highly significant between patients
      with and without complications (p < 0.001) as well as between survivors and non
      survivors (p < 0.001). Furthermore in patients underlying shock-phases in the
      course of treatment significantly higher elastase values are measured as in the
      patients remaining (p < 0.001). The highest prognostic evidence is determined by
      the elastase at the 9th day of course of disease concerning the prediction of a
      patient's death (sensitivity 78%, specificity 75%, positive predictive value 63%,
      respectively negative predictive value 87%).

PMID- 7801407
TI  - [Baker's cyst--a pre-arthrotic factor?].
AB  - Between July 1989 and 1994 127 Baker-cysts have been operated and histologically
      examined with synovial biopsies out of the same knee. All Baker-cysts and
      synovial biopsies - including out of synovial membranes without macroscopically
      pathological findings and without other pathological intraarticular causal
      lesions - revealed a chronic synovitis. The Baker-cyst has to be regarded as a
      primary or secondary causative factor of chronic effusions and involves the
      development of a chronic synovitis by the disorder of the synovial and hydraulic
      system of the knee-joint. The exstirpation of the Baker-cyst as a prearthrotic
      factor is advised therefore.

PMID- 7801408
TI  - [Surgical treatment of diaphyseal tibial fractures. Choice of procedure and
      results of treatment of 187 fractures].
AB  - From 1988 to 1990 a total of 187 fractures of the tibia (92 compound, 95 closed
      fractures) were treated with a primary osteosynthesis. In 102 fractures an
      external fixation was performed, 85 internal fixations were divided into 58
      intramedullary nails and 27 plates. In a follow-up study the fracture healing was
      analysed, 90% of the patients were examined about 18 months after the accident.
      The mean healing time was between 12 weeks (internal fixation) and 16 weeks
      (external fixateur). After primary Fixateur externe 54 were treated by secondary
      internal fixation, intramedullary nailing was the method of choice. Contamination
      rate of the tibia, taken by an intraoperative wound swab before nailing was 30%.
      Infection occurred in 3.2%, non union and refractures in 1.5% and 1%. Over all
      80% excellent and good results were found after consolidation. 10% fair and 10%
      bad results including three amputations after III degrees compound fractures and
      three death after polytrauma.

PMID- 7801409
TI  - [Is remodeling still possible after collapse in femur head necrosis?].
AB  - A case of a femoral head necrosis, with collapsed joint surface after fracture of
      the femoral neck will be presented. Following varisation osteotomy, the necrotic
      parts of the bone was removed and filled with cancellous bone. A standardized
      bone block of the iliac crest was implanted into the hole. After the operation
      the patient was painfree. The X-rays showed the improvement of the bony structure
      and later a spherical remodeling of the femoral head. This result is in
      opposition with the earlier opinion of the disability of femoral head remodeling
      in adults. It is technically very important to pack tight the hole in the femoral
      head with cancellous bone chips after necrectomy, and to ensure the
      revascularisation with vascularised bone block.

PMID- 7801410
TI  - [Electronic picture and data storage and processing with PC in trauma surgery--an
      anachronism?].
AB  - Acquisition, storage and processing of any images relevant in trauma surgery
      together or in combination with (alpha) numeric data nowadays are possible
      employing a personal computer. The computing speed that is achieved with 486
      cpu's "inside" is sufficient to process images in motion as well as single images
      to be filtered. The display and process-resolutions required for processing of X
      ray-images can be achieved with the PC's hardware as well as with the software
      available. That is why there is no need any longer for special configurations for
      X-ray-departments. Calculating the price of the process-environment proposed,
      about 25,000 DM should be enough including the video tape recorders and the CD
      ROM-recorder that are required.

PMID- 7801411
TI  - [Infection statistics].

PMID- 7801412
TI  - Hydronephrosis due to fibroepithelial ureteral polyp in a child.
AB  - The case of a 5-year-old girl, complaining of left abdominal and flank pain, is
      reported. The excretory urogram and retrograde pyelography showed an obstruction
      located at the left upper ureter with hydronephrosis. Exploration revealed a
      small ureteral polyp obstructing the lumen. The polyp along with the short
      segment of the ureter was resected. Diagnostic and therapeutic considerations are
      discussed.

PMID- 7801413
TI  - Lymphangioma of the urethra.
AB  - We report a case of urethral lymphangioma presenting with frank, painless
      hemaluria as the only symptom. Such a case has not been described in the
      literature to our knowledge.

PMID- 7801414
TI  - Pericentric inversion of chromosome 9 associated with chordee without hypospadia.
AB  - We report a case of pericentric inversion of chromosome 9 associated with chordee
      without hypospadia. Plasma levels of LH and testosterone were within normal
      ranges, but the plasma FSH level was slightly elevated. The LH response to LH-RH
      stimulation and the response of plasma testosterone to HCG were normal. However,
      the administration of LH-RH induced an abnormally low response of plasma FSH.

PMID- 7801415
TI  - Adenocarcinoma of the urachus showing extensive calcification and stromal osseous
      metaplasia.
AB  - We report a case of adenocarcinoma of the urachus showing extensive calcification
      and stromal osseous metaplasia, arising in the bladder dome of a 51-years-old
      man. The patient underwent partial cystectomy, including in block excision of the
      entire urachus and umbilicus, and remains well, free from symptoms after a 22
      month follow-up period. Main pathologic and clinical characteristics of urachal
      calcified tumors are reviewed. To our knowledge, this is the first report in the
      English literature on urachal carcinoma showing both extensive scattered
      calcification and massive stromal osseous metaplasia.

PMID- 7801416
TI  - Two cases of inflammatory skin metastasis from transitional cell carcinoma of the
      urinary bladder.
AB  - Two rare cases of inflammatory skin metastasis from transitional cell carcinoma
      of the urinary bladder were reported.

PMID- 7801417
TI  - Renal tissue endothelin in long-term complete ureteric obstruction in the young
      rat.
AB  - Complete obstruction of one ureter was created in 3-week-old weanling rats. The
      endothelin concentration in the renal tissue was measured by radioimmunoassay. In
      the obstructed kidney, a substantial increase was observed, after 1 week +90%,
      after 2 weeks +55%, and after 4 weeks +145% compared to the control rat kidneys.
      The endothelin-1/endothelin-3 ratio was found to be considerably raised,
      indicating a predominance of the vasoconstrictor effects of the--with reference
      to vasoactivity--bi-potential endothelin. Its contribution to vasoconstriction
      and to glomerular destruction in obstructive nephropathy is discussed.

PMID- 7801418
TI  - Segmental differences in the density of autonomic receptors in dog vas deferens.
AB  - In order to study the segmental difference in the density of autonomic receptors
      of the vas deferens, we measured the amount of adrenergic alpha 1-, alpha 2- and
      beta-receptors and muscarinic cholinergic receptors in the three portions
      (prostatic, intermediate and epididymal) of dog vas deferens using radioligand
      binding techniques. Saturation experiments with 3H-prazosin, 3H-yohimbine, 3H
      dihydroxyalprenolol and 3H-quinuclidinyl benzilate demonstrated that three were
      significant amounts of adrenergic alpha 1-, alpha 2- and beta-receptors and
      muscarinic cholinergic receptors in the three portions of dog vas deferens. Of
      the three portions examined, the prostatic portion was found to have a larger
      amount of alpha 1-, alpha 2-receptors and muscarinic receptors, while the
      intermediate portion was found to have a larger amount of beta-receptors. The
      epididymal portion was found to have a smaller amount of autonomic receptors.
      These data suggest that the prostatic portion plays a more important role in the
      function of the dog vas deferens. It is thought that the different segments of
      the vas deferens have a different functional role according to the distribution
      of autonomic receptors.

PMID- 7801419
TI  - Preoperative urodynamic evaluation: does it predict the degree of urinary
      continence after radical retropubic prostatectomy?
AB  - Preoperative evaluation of voiding patterns and detailed urodynamic evaluation
      before radical retropubic prostatectomy was carried out in an attempt to identify
      patients at higher risk of developing urinary incontinence postoperatively.
      Ninety-two men, mean age 64 years (range 54-72), who completed 1 year of follow
      up after radical retropubic prostatectomy for clinically localized adenocarcinoma
      of the prostate were included in the study. According to the preoperative
      urodynamic findings, patients were divided into two main groups: group 1 (n = 64)
      patients with normal urodynamic findings, and group 2 (n = 28) patients with
      abnormal urodynamic findings. The latter group was further subdivided according
      to the abnormality: detrusor instability (n = 12), weak sphincter mechanism (n =
      9), and detrusor and sphincter instability (n = 7). The degree and incidence of
      urinary incontinence were evaluated in both groups at the 1-year follow-up visit.
      There was a substantial difference in the incidence of urinary incontinence
      between the two main groups with only 2 patients with incontinence in group 1
      (3%) versus 11 patients in group 2 (39%). In addition, the incidence of
      incontinence in group 2 differed depending on the type of abnormality: the lower
      incidence occurred in patients with detrusor instability (17%) and the higher
      incidence in patients with both detrusor and sphincter instability (71%).
      Identification of sphincteric and bladder dysfunction preoperatively may indicate
      a high risk of urinary incontinence after radical prostatectomy.

PMID- 7801420
TI  - Deteriorated arterial supply to the lower limb during oral oestrogen therapy of
      patients with prostatic carcinoma.
AB  - Patients with prostatic carcinoma were randomised to treatment with surgical
      castration (n = 47) or oral oestrogen therapy (n = 53). The oestrogen-treated
      patients received oral ethinyl oestradiol daily, 1 mg for the first 2 weeks
      followed by 150 micrograms. In addition, oestrogen was given intramuscularly as
      polyoestradiol phosphate monthly 160 mg for 3 months, continued by 80 mg. Before
      and 1 year after therapy systolic arm and toe blood pressures were measured.
      Eleven percent of the patients in the oestrogen group had a pathological pressure
      difference between the arm and toe before treatment versus 34% in the
      orchidectomy group. Despite the greater proportion of subclinical atherosclerotic
      disease in the legs of the patients in the orchidectomy group, the patients in
      the oestrogen group only had signs and symptoms of a deterioration of the
      arterial system. Thus, in the oestrogen group the arm-toe blood pressure
      difference increased from 20 +/- 3 to 32 +/- 4 mm Hg (p < 0.001) and the
      proportion of pathological toe pressures increased from 11 to 29% (p = 0.0014).
      Two of the patients in this group had to be referred for reconstructive surgery
      due to severe intermittent claudication. In addition, 5 more patients in this
      group suffered arterial ischemic events in the coronary and cerebral
      vasculatures. In contrast, there were no clinical ischemic events in the
      orchidectomy group and no change in the blood pressure difference between the arm
      and toe 1 year after orchidectomy. In conclusion, oral oestrogen therapy, in
      contrast to orchidectomy, induces a deterioration of the arterial supply to the
      lower limbs during the 1st year of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7801421
TI  - Renal cell carcinoma in dialysis patients.
AB  - Histopathological studies were performed in 18 dialysis patients with renal cell
      carcinoma. All patients were classified as stage I according to the criteria in
      the protocol of Robson. The 2 main cell types in these patients were granular
      (50%) and clear (44%) cell tumors. Thirty-nine percent of the carcinomas
      exhibited a predominantly acinar growth pattern, 27% had a papillary, and 17%
      exhibited a cystic growth pattern. In 28 nondialysis patients, the commonest cell
      type was clear cell carcinoma (67%) and acinar growth pattern was the predominant
      one (67%). The incidence of papillary renal cell tumors in dialysis patients was
      significantly higher than in nondialysis patients (p < 0.05). Patients with
      papillary renal cell tumors had received longer duration of dialysis therapy than
      those with nonpapillary renal cell carcinomas (p < 0.05). Seven (39%) showed
      grade 1 carcinoma and 11 (61%) showed grade 2, but grade 3 carcinoma was not
      observed. In these patients, 8 had associated acquired cystic disease of the
      kidney (ACDK). The duration of dialysis in the patients with ACDK was
      significantly longer (p < 0.001). The most frequent cell type was granular-cell
      carcinoma (63%) in the patients with ACDK. Six patients without ACDK (60%) showed
      clear-cell carcinoma and 4 (40%) had granular cell tumors. Seventy-four percent
      of carcinomas exhibited a predominantly either papillary or cystic growth pattern
      in the patients with ACDK. However, renal cell carcinomas in dialysis patients
      with or without ACDK did not show significant differences in growth
      pattern.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7801422
TI  - Risk factors predisposing to repeated extracorporeal shockwave lithotripsy.
AB  - The Victorian Lithotripsy Service is geographically unique, representing the only
      Australian lithotripter for a 900-km radius and serving a patient population of
      over 3 million, and 26 accredited operator urologists. Because of distance and
      health service constraints few patients treated for renal calculi on this machine
      have the opportunity to seek additional treatment by extracorporeal shockwave
      lithotripsy (ESWL) elsewhere. The treatment histories of all patients who
      underwent ESWL at this center over a 4-year period were examined, with those
      patients who required ESWL on more than one occasion being identified and their
      treatment details reviewed. The retreatment rate was approximately 6%. In
      patients who required three or more ESWL treatments multiple calculi were present
      significantly more often than in the overall cohort (p < 0.05), and ESWL alone
      was ultimately successful in obtaining satisfactory stone fragmentation in only
      62% of this group. In view of the high cost of repeated treatments by ESWL the
      applicability of this treatment method in cases of multiple calculi should be
      questioned. Initial undertreatment of calculi may also represent a significant
      factor in the retreatment of some radiopaque calculi.

PMID- 7801424
TI  - Gunshot wounds of the male external genitalia.
AB  - The explosive increase of violence in our society has imposed hazards of gunshot
      injuries on the civilian population. The genitourinary system is no longer
      exempted from such assaults. Although male external genitalia are amongst less
      commonly involved organs, in a span of 14 months, 4 such cases were managed at
      our institute. Our experience of such injuries is being highlighted so as to draw
      attention to their increasing incidence and association with injuries of other
      organs. Three patients had haemorrhagic shock at initial presentation. They were
      managed by resuscitation, debridement and repair of wounds Urethral injuries were
      dealt initially by diversion and subsequently urethroplasty was performed. In a
      follow-up of 6-12 months, all the patients were reported to be having normal
      erections and none of them have developed urethral stricture.

PMID- 7801423
TI  - In situ extracorporeal shockwave lithotripsy of distal ureteral stones:
      parameters for therapeutic success.
AB  - Between January and December 1989, 123 patients with distal ureteral stones were
      treated with in situ extracorporeal shockwave lithotripsy (ESWL) using a modified
      HM3 Dornier lithotriptor. One hundred and three patients (83.7%) were stone-free,
      20 patients (16.3%) had small residual stones (< 1 mm2) that passed
      spontaneously. In situ ESWL treatment alone was successful in 88 of the 103 stone
      free patients (85.4%). Fifty-six (54.4%) needed 1 ESWL session, 26 (25.2%) needed
      2 ESWL sessions. Nineteen of the 123 patients (15.4%) needed auxiliary
      endourological measures. The results of ESWL treatment were correlated to
      pretherapeutically identified parameters such as stone size, radiopacity, outer
      contour, shape, inner structure, biochemical analysis of the stones and grade of
      dilatation of the upper urinary tract. The results prove that size (> or = 75
      mm2), radiopacity and grade of dilatation have a direct correlation to the
      difficulty to disintegrate ureteral stones.

PMID- 7801425
TI  - Blunt traumatic rupture of the high right ureter, repaired with appendix
      interposition.
AB  - We report the first case of upper lumbar ureteral replacement with the vermiform
      appendix, in a blunt traumatic ureter rupture with important urinoma. In selected
      cases, in which the appendix has a required caliber and length, the vermiform
      appendix is a very good autograft for ureteral substitution. The vermiform
      appendix must be preserved if possible in the abdominal surgery.

PMID- 7801426
TI  - Selective transcatheter embolization of a pediatric postnephrectomy arteriovenous
      fistula.
AB  - A rare case of postnephrectomy arteriovenous fistula of the right renal pedicle
      of a 6-year-old boy is reported. The diagnosis was made by clinical signs and
      confirmed by colored duplex sonography and angiography. Successful treatment was
      achieved by percutaneous transcatheter embolization using coils.

PMID- 7801427
TI  - Cardiovascular lesions in bovine Marfan syndrome.
AB  - Bovine Marfan syndrome is a genetic disease with many of the clinical and
      pathologic manifestations of human Marfan syndrome. Major manifestations include
      ectopia lentis and aortic dilatation, aneurysm, and rupture. Affected cattle have
      a defect in fibrillin metabolism similar to that in human patients. Ten cattle
      were followed and their disease progression and lesions documented. Ages ranged
      from a term fetus (No. 9) to a 4-year-old cow (No. 4); three animals were male
      (Nos. 1-3) and seven were female (Nos. 4-10). Of eight animals (80%) that died or
      were euthanatized (Nos. 1-3, 5-9), six (75%) had severe cardiovascular lesions
      identified at necropsy. Gross cardiovascular lesions of bovine Marfan syndrome
      included cardiac tamponade secondary to aortic rupture (animal Nos. 3, 6, 8),
      dissecting aneurysms of the aorta and pulmonary artery (animal No. 5), and
      intrauterine cardiac tamponade secondary to rupture of the pulmonary artery
      (animal No. 9). Microscopically, Verhoeff Van Gieson-stained sections of aorta
      contained severe fragmentation of the elastic laminae in the aortic media, but
      the cystic medial necrosis seen in human Marfan aortae was not identified, even
      in the chronic aortic dissection. Ultrastructurally, affected aortic tissue was
      characterized by thin, dark elastic fibers with abundant, tangled microfibrils on
      the periphery. Swirls of collagen fibers and bundles of hypertrophic smooth
      muscle cells replaced damaged elastic laminae. Gross and microscopic
      cardiovascular lesions in bovine Marfan syndrome are similar to those in human
      Marfan syndrome. Bovine Marfan syndrome is a valuable model for investigation of
      molecular pathogenesis and treatment of human Marfan syndrome.

PMID- 7801429
TI  - Equine glucose-6-phosphate dehydrogenase deficiency.
AB  - Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a well-characterized X
      linked inherited disorder in humans but has not been reported in horses. We
      describe a persistent hemolytic anemia and hyperbilirubinemia due to a severe
      G6PD deficiency in an American Saddlebred colt. Other abnormalities in the colt's
      erythrocytes as compared with those of healthy horses (n = 22-35) included
      increased activities of hexokinase and pyruvate kinase, decreased concentrations
      of reduced glutathione and reduced nicotinamide adenine dinucleotide phosphate
      (NADP), and increased concentration of oxidized NADP. Morphologic abnormalities
      included eccentrocytosis, pyknocytosis, anisocytosis, macrocytosis, and increased
      number of Howell-Jolly bodies. Scanning and transmission electron microscopic
      examinations revealed that eccentrocytes had contracted to spherical regions and
      thin collapsed regions. Eccentrocytes were more electron dense than were normal
      erythrocytes when examined by transmission electron microscopy. When exposed to
      acetylphenylhydrazine, erythrocytes from the G6PD-deficient colt produced more
      and smaller Heinz bodies than did erythrocytes from normal horses. Abnormalities
      in the colt's dam included presence of eccentrocytes and pyknocytes; her average
      erythrocyte G6PD activity was slightly below the range of reference values.

PMID- 7801428
TI  - Malignant rhabdoid tumor in the gastric wall of an aged orangutan (Pongo
      pygmaeus).
AB  - A 34-year-old female orangutan (Pongo pygmaeus) developed renal failure and
      became uremic. At necropsy, large gastric masses were present around the cardia
      and in the corpus. Abdominal metastases occurred in the liver, pancreas, and
      right ovary. Light microscopic examination of the tumor revealed polygonal cells
      with vesicular nuclei and prominent nucleoli. The growth pattern was
      predominantly solid. Focal areas contained excentric cytoplasmic intermediate
      filament inclusions, as identified by immunohistochemistry and electron
      microscopy. Immunohistochemical procedures demonstrated mainly the vimentin type
      of intermediate filaments. Except for occasional cytokeratin, other intermediate
      filament markers and neural, lymphocytic, and histiocytic markers stained
      negative. The morphologic and ultrastructural characteristics are typical for a
      malignant rhabdoid tumor, a term used in human pathology to describe a rare and
      extremely aggressive malignancy of uncertain histogenesis. Although usually
      located in the infant kidney, a few reports have documented the occurrence of
      similar lesions in extrarenal sites of adults. In human tumors, vimentin is often
      combined with the expression of cytokeratins. The sparsity of the cytokeratin
      filaments in this case might be due to species-specific variations and/or may
      reflect the hypothesis of a phenotypic concept encompassing a spectrum of
      histogenetic diversity.

PMID- 7801430
TI  - Diagnostic and prognostic importance of chromosomal aberrations identified in 61
      dogs with lymphosarcoma.
AB  - To determine the diagnostic and/or prognostic importance of chromosomal
      aberrations identified in dogs with malignant (non-Hodgkin's) lymphoma, clinical
      stages for 61 dogs with lymphosarcoma were determined, the lymph node(s) were
      histopathologically graded, and the malignant tissue lymphocytes were karyotyped.
      The results from life table survival curve analysis demonstrated that first
      remission length and survival time were significantly longer in 15 of 61 (25%)
      dogs that had a trisomy of chromosome 13 as the primary chromosomal aberration
      than in those dogs (46/61, 75%) with other primary chromosomal aberrations (P <
      0.05). Sex, age, weight, histopathologic subtype and grade, World Health
      Organization (WHO) clinical stage, WHO and modified Karnofsky performance status,
      chromosomal modal number, and treatment protocol were of no prognostic importance
      in predicting first remission length or survival time (P > 0.05). Multivariate
      analysis did not identify a significant correlation between the prognostic groups
      or within the various prognostic subsets (P > 0.05). The pathogenesis of canine
      and human non-Hodgkin's lymphoma, as observed cytogenetically, differs.

PMID- 7801431
TI  - Testicular maturation in prepubertal New Zealand white rabbits.
AB  - Testicular maturation was assessed in age-matched, sexually immature (13-17-week
      old) New Zealand white rabbits using end points frequently evaluated in toxicity
      studies: testicular weight and testicular histology. Testicular weights and
      testicular maturity as assessed histologically were markedly variable in sexually
      immature rabbits, especially at > or = 14 weeks of age. The large variation in
      testicular weights in immature rabbits requires that large changes in a treatment
      group relative to controls be present for statistical detection of testicular
      weight effects at commonly used significance levels. Testicular weights and
      testicular maturity were strongly correlated to one another, but neither weight
      nor maturity was strongly correlated to body weight. Thus, stratification and
      randomization of immature rabbits to study groups based upon body weight will not
      assure an absence of group differences with respect to testicular maturity. The
      large variation in testicular weights and maturity in 13-17-week-old rabbits
      warrants caution in the evaluation of testicular changes when rabbits of this age
      range are used in toxicity studies.

PMID- 7801432
TI  - Vascular mineralization in the monkey brain.
AB  - Mineralization of various degrees was found in the brains of 79 (59%) of 134
      cynomolgus monkeys (Macaca fascicularis). There was no age dependency in the
      incidence or severity, nor were there any abnormalities in growth, weight gain,
      or neurologic signs, although a slight sex difference was observed. The lesions,
      which were basophilic and intensely positive for periodic acid-Schiff or von
      Kossa stain, occurred in the vascular walls of the globus pallidus in two types:
      globoid bodies with prominent concentric lamellar structures in and around the
      arteriolar and venular wall (type A) and fine granules in the media of small or
      medium-sized arteries (type B). Electron microscopic examination revealed dense
      deposits in the degenerated media of small or medium-sized arteries or the
      thickened walls of the arterioles. X-ray microanalysis demonstrated the presence
      of calcium, phosphorus, iron, zinc, magnesium, and aluminum.

PMID- 7801433
TI  - Detection of activated feline platelets in platelet-rich plasma by use of
      fluorescein-labeled antibodies and flow cytometry.
AB  - Platelets contribute to prethrombotic or thrombotic states; however, accepted
      evaluation methods (i.e., in vitro testing by use of an aggregometer) of platelet
      function in cats can be difficult because of the large volume of blood required
      from which platelets are isolated and the potential for platelet activation due
      to difficult venipunctures in sometimes uncooperative or excited animals. The
      activation problem also contributes to errors in platelet counts. Platelets from
      four domestic short haired cats (two males, two females, 2-3 years old) minimally
      restrained without sedation or anesthesia were evaluated. Blood (5 ml) was
      collected by jugular venipuncture directly into syringes containing 3.8%
      trisodium citrate (nine parts blood to one part anticoagulant) plus prostaglandin
      E1 (3 microM; 0.25, 0.5, 1, or 2 microliters/500 microliters citrate) or 3.8%
      trisodium citrate alone. Prostaglandin E1, which is a stable metabolite of
      arachidonic acid with platelet inhibitory properties similar to those of
      prostaglandin I2, was added to the anticoagulant to prevent activation of
      platelets during the collection process. Feline platelets exposed to
      prostaglandin E1 became immediately and persistently nonreactive to agonists,
      which negated their use in functional studies (aggregation, 14C-serotonin
      release, binding of fluorescein-conjugated antifibrinogen) but improved platelet
      counting accuracy. Detection of in vivo activation of platelets in prethrombotic
      and thrombotic states in humans has been done by identification of activation
      dependent molecules on platelet surfaces by use of specific antibody recognition
      and detection by flow cytometric analysis. Many activation-dependent platelet
      surface receptor changes are species specific; however, fibrinogen appears to be
      conserved across species.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7801434
TI  - Squamous metaplasia of bronchiolar cell-derived adenocarcinoma induced by N
      nitrosomethyl-n-heptylamine in Syrian hamsters.
AB  - Morphology and development of experimental bronchiolar lung tumors were studied
      in Syrian hamsters, using light and electron microscopic techniques. At the age
      of 9 weeks, 46 hamsters were each given one weekly gavage of 6.8 mg N
      nitrosomethyl-n-heptylamine for 35 weeks, and hamsters were examined at intervals
      from 2 to 46 weeks. The present report describes the progression of
      adenocarcinomas of bronchiolar cell origin to adenosquamous and squamous cell
      carcinomas. Squamous metaplasia was commonly noted at the tumor periphery, i.e.,
      zone of growth. In 20 hamsters, 22 adenosquamous and two squamous cell carcinomas
      (one a large cell carcinoma) were diagnosed by light microscopy. Overt
      keratinization was infrequent. Squamous cell metaplasia was not a feature of
      papillary neoplasms but was seen mainly with acinar structures.
      Ultrastructurally, squamous differentiation (metaplasia) appeared to develop
      along two different pathways. First, secretory cells were observed with large
      numbers of intermediate filaments and tonofilaments, with concurrent loss of
      organelles such as secretory granules and microvilli. Second, squamous metaplasia
      also appeared to develop from a progeny of tumor cells that failed to mature into
      secretory cells. Such cells were often present within the basal layer of
      secretory acini and resembled basal cells of the tracheobronchial tree. These
      observations were supported by increased expression of cytokeratins, as revealed
      by immunohistochemical procedures. Immunoelectron microscopic examination
      localized hamster Clara cell antigen in secretory granules of neoplastic Clara
      cells, in the cytoplasm between granules, and at the microvillous border. With
      the onset of squamous differentiation, Clara cell antigen was progressively lost
      from secretory cells and was only rarely seen in cells with tonofilaments. No
      labeling was present in squamous cells arising at the base of tumor acini. These
      results suggest that pulmonary squamous cell carcinomas may develop by direct
      squamous differentiation of secretory cells or may proceed from undifferentiated
      tumor cells.

PMID- 7801435
TI  - 'Exceptionally busy year' for the SVS.

PMID- 7801436
TI  - Further cases of necrotic enteritis in calves.

PMID- 7801437
TI  - An evaluation of humane gas stunning methods for turkeys.
AB  - Spontaneous electroencephalograms (EEG) and somatosensory evoked potentials
      (SEPS) were recorded in turkeys while they were kept in an atmosphere of either
      49 or 86 per cent carbon dioxide in air. The time to the loss of SEPS was not
      related to the concentration of carbon dioxide, but the time to the onset of an
      isoelectric EEG was shorter at the higher concentration of carbon dioxide. In
      comparison with other gas stunning methods it was considered that stunning with
      these high concentrations of carbon dioxide would not have any welfare advantages
      over stunning in argon with 2 per cent residual oxygen or in a mixture of 30 per
      cent carbon dioxide and 60 per cent argon in air.

PMID- 7801438
TI  - Detection of louping ill virus in formalin-fixed, paraffin wax-embedded tissues
      of mice, sheep and a pig by the avidin-biotin-complex immunoperoxidase technique.
AB  - An immunohistochemical method for the detection of louping ill virus antigen in
      formalin-fixed, paraffin wax-embedded tissues by an avidin-biotin-complex (ABC)
      immunoperoxidase technique was established. The tissues examined were from the
      brains of 10 mice, five sheep and one pig. The mice were experimentally infected
      with louping ill virus whereas the sheep and the pig were field cases of louping
      ill confirmed by clinical examination, and by histological and serological
      methods.

PMID- 7801439
TI  - Changes in blood lactate and heart rate in thoroughbred horses during swimming
      and running according to their stage of training.
AB  - The purpose of this study was to investigate whether the change in the
      performance capacity of horses trained by running could be evaluated with a
      standardised swimming exercise test as well as by a standardised running exercise
      test. Seven two-year-old thoroughbred horses were trained by running for four
      months and were subjected to a standardised swimming exercise tolerance test
      before the training began and after two and four months of training in addition
      to the standardised running tolerance test after two and four months of training.
      The running training brought about a significant change in the correlation
      between the swimming speed of the horses and their blood lactate concentration,
      and the correlation between the blood lactate concentration and maximum heart
      rate and running speed also changed significantly after two months of training.

PMID- 7801440
TI  - Neurological manifestation of cholesterinic granulomas in three horses.
AB  - Cholesterinic granulomas have been previously reported as an incidental post
      mortem in horses. Three adult horses with diencephalic dysfunction due to
      cholesterinic granulomas are described. All the horses exhibited profound
      depression, somnolence and reluctance to move. One horse experienced generalised
      seizures. Cerebrosinal fluid was xanthochromic with an elevated total protein in
      two of the cases evaluated. The large cholesterinic granulomas caused expansion
      of the lateral ventricle and secondary hydrocephalus due to the build up of
      cerebrospinal fluid behind the mass. Cholesterinic granulomas are believed to
      result from choroid plexus congestion and haemorrhage.

PMID- 7801441
TI  - Microfilariae in the mammary gland of a bitch.
AB  - A microfilarial infection of the mammary gland of a bitch with Dirofilaria
      immitis was diagnosed by fine needle aspiration biopsy. The animal had had a
      progressively enlarging, painful, pendulous, cystic swelling, measuring 12 x 18
      cm, in the second left abdominal mammary gland for four to five months. Two
      separate biopsies revealed microfilariae and mammary duct epithelial cells, but
      no inflammatory cells. A histological examination revealed atrophic and necrotic
      mammary lobules with dilated and cystic ducts. Solid carcinoma was also observed
      in a small area of the mammary mass. The interlobular connective tissue was
      oedematous and the lymphatic and vascular channels were dilated. Microfilariae
      were observed within both the small blood vessels and capillaries and in the
      interlobular stroma of the mammary tissue, but there was no evidence of an
      inflammatory response.

PMID- 7801442
TI  - Acute exudative pneumonia and airsacculitis associated with Ornithobacterium
      rhinotracheale in turkeys.

PMID- 7801444
TI  - Equine intrapericardial lipoma.

PMID- 7801443
TI  - Myopathy and pancreas disease in salmon: a retrospective study in Scotland.

PMID- 7801445
TI  - Future of CPD.

PMID- 7801446
TI  - Hospital standards.

PMID- 7801447
TI  - Hospital standards.

PMID- 7801448
TI  - Hospital standards.

PMID- 7801449
TI  - Use of veal crates.

PMID- 7801450
TI  - OVS red meat hygiene refresher courses.

PMID- 7801451
TI  - Equine herpesvirus-1: a neurotropic alphaherpesvirus.

PMID- 7801452
TI  - Use of ELISAs in the diagnosis of canine atopy.

PMID- 7801453
TI  - Government policy concerning zoonotic diseases in The Netherlands.

PMID- 7801454
TI  - Toxocara infection in children and the relation with allergic manifestations.

PMID- 7801455
TI  - Toxocarosis in dogs and cats.

PMID- 7801456
TI  - Infertility in the bitch.

PMID- 7801457
TI  - Canine pediatrics.

PMID- 7801458
TI  - Diagnosis, therapy, and prevention of common infectious diseases in the dog.

PMID- 7801459
TI  - Aspects of obstetric care in the dog.

PMID- 7801460
TI  - Diagnosis, pathogenesis, and treatment of neck lesions in cats.

PMID- 7801461
TI  - Current veterinary therapy in canine osteosarcoma.

PMID- 7801462
TI  - Diffuse neuromuscular disorders.

PMID- 7801463
TI  - Seizures and behavioral abnormalities in dogs and cats with neurological
      dysfunction.

PMID- 7801464
TI  - Prognostic factors for malignant lymphoma in the dog: an update.

PMID- 7801465
TI  - Growth and growth hormone in the dog.

PMID- 7801466
TI  - Choosing between medical and veterinary clinical laboratories.

PMID- 7801467
TI  - Recent advances in dietary management of hepatic diseases.

PMID- 7801468
TI  - Evaluation of pet foods.

PMID- 7801470
TI  - An introduction to ultrasonographic imaging.

PMID- 7801469
TI  - Calcium chloride as urinary acidifier in relation to its potential use in the
      prevention of struvite urolithiasis in the cat.

PMID- 7801471
TI  - Ultrasonography of the thoracic cavity.

PMID- 7801472
TI  - Basic principles of abdominal radiography.

PMID- 7801473
TI  - Diseases and management of pet fishes.

PMID- 7801474
TI  - Some guidelines to the anesthesia of exotic animals.

PMID- 7801475
TI  - Differential approach to house-soiling by dogs and cats.

PMID- 7801476
TI  - Differential approach to aggression by dogs and cats.

PMID- 7801477
TI  - Fly snapping syndrome in dogs.

PMID- 7801478
TI  - Pathological anticipatory defence behavior in dogs.

PMID- 7801479
TI  - Diagnosis, therapy, and prevention of common infectious diseases in the cat.

PMID- 7801480
TI  - Social problem behavior in dogs: etiology and pathogenesis.

PMID- 7801481
TI  - Somatic problems as a risk factor for behavior problems in dogs.

PMID- 7801482
TI  - Commonly encountered feline behavior problems.

PMID- 7801484
TI  - Dogs have feelings.

PMID- 7801483
TI  - Social behavior of wolves and dogs.

PMID- 7801485
TI  - Disciplinary law.

PMID- 7801486
TI  - What does vaccination mean to your clients?

PMID- 7801487
TI  - Marketing in my practice.

PMID- 7801488
TI  - For or against lens implantation in dogs.

PMID- 7801489
TI  - CT and ultrasonographic diagnosis of canine hydrocephalus.

PMID- 7801490
TI  - Nose prints as a method of identification in dogs.

PMID- 7801491
TI  - A prospective study of a commercial hypoallergenic diet in 18 dogs.

PMID- 7801492
TI  - Diabetes insipidus in a dog with an alpha MSH-producing pituitary tumor.

PMID- 7801493
TI  - Intracranial tumors: a diagnostic challenge.

PMID- 7801494
TI  - Mycosis fungoides: a dermatological puzzle.

PMID- 7801495
TI  - Coccidioidomycosis in a dog.

PMID- 7801496
TI  - Efficacy and safety of vaccines.

PMID- 7801497
TI  - Some aspects of vaccination in companion animal practice.

PMID- 7801498
TI  - Accessory carpal bone fractures in the horse.
AB  - The clinical signs, the radiographic appearance, and the treatment of two cases
      of fracture of the accessory carpal bone are described. The fractures were in the
      vertical plane. Surgical intervention consisted out of fixation of the fracture
      with two lag screws. Follow-up information revealed that one horse became sound
      and returned to complete athletic activity whereas the other horse remained lame.
      A brief literature review is given and the surgical treatment and the
      complications are discussed.

PMID- 7801499
TI  - Cancellous bone grafting in the treatment of bovine septic physitis.
AB  - Eleven young cattle (8-24 months of age) were treated for septic physitis of the
      metacarpal or metatarsal bones. Two new elements were added to the traditional
      treatment. Firstly, homologous cancellous bone grafts were used for their
      osteoinductive properties even in an infected surrounding. (Actinomyces pyogenes
      was recovered most commonly.) Secondly, a walking cast was applied for better
      immobilization of the lower limb with minimal discomfort to the animal. After
      surgery, the 11 bovine patients needed an average walking cast period of 4.5
      weeks and 1 to 2 weeks' treatment with antibiotics. The new treatment regime
      expedites the healing process and shows a success rate of 100%. Follow-up after 6
      months revealed that all animals were completely sound without recurrence of the
      physitis.

PMID- 7801500
TI  - A modified technique for implantation of polypropylene mesh for the repair of
      external abdominal hernias in horses: a review of 21 cases.
AB  - During a 3-year period 21 horses were surgically treated because of large
      abdominal wall defects. In each case the defect was bridged with a polypropylene
      mesh, which was placed on the outside of the hernial ring. This was in contrast
      with the technique for mesh herniorrhaphy generally described in human and
      veterinary literature, in which the mesh is always implanted on the inside of the
      hernial ring. One horse was destroyed on the first postoperative day because of
      postanaesthetic myelomalacia. Surgical repair as described was successful in 18
      patients. Recurrence of herniation occurred in two horses. On re-herniorrhaphy a
      second and larger mesh was successfully implanted.

PMID- 7801501
TI  - Single intraoperative administration of antibiotic to cows with caecal torsion:
      wound infection and postoperative performance. A retrospective and prospective
      study.
AB  - Wound infection and postoperative performance after a single intra-abdominal
      administration of 9 g sodium ampicillin in cows operated on for caecal dilatation
      or torsion (n = 33) were evaluated. In the 25 animals that left the clinic in
      good health (76% short-term survival), no wound infection occurred. Postoperative
      performance was normal in 21 of these animals (84%). The figures for short-term
      survival and postoperative performance are comparable to those from a
      retrospective study of 169 animals operated on between 1985 and 1990. Single
      intra-abdominal administration of sodium ampicillin during surgery provides good
      protection against infection without negative effects on the postoperative
      performance.

PMID- 7801502
TI  - Oral bioavailability of pivampicillin in foals at different ages.
AB  - The plasma disposition of ampicillin after intravenous administration at a dose
      rate of 15 mg/kg was studied in six healthy, 1-month-old foals. The oral
      bioavailability of pivampicillin was determined in the same foals at four ages,
      ranging from 11 days to 4 months. Pivampicillin was administered orally at a dose
      rate of 19.9 mg/kg, which is equivalent on a molecular basis to 15 mg/kg
      ampicillin. Ampicillin concentrations in plasma were determined up to 12 hours
      after administration. After intravenous administration, the mean distribution and
      elimination half-lives of ampicillin were 0.121 and 0.624 h, respectively. The
      volume of distribution (Vss) appeared to be 0.334 l/kg. Orally administered
      pivampicillin was rapidly absorbed in all age groups, producing mean peak plasma
      concentrations of 3.83 to 5.69 micrograms/ml 1 h after administration. The mean
      bioavailability of pivampicillin in the different age groups ranged from 39.4 to
      52.9%. There was no statistically significant difference in peak plasma
      concentration or bioavailability between the age groups. It is concluded that
      pivampicillin at a dose rate of 19.9 mg/kg orally gives satisfactory plasma
      concentrations in foals of all ages.

PMID- 7801503
TI  - Laboratory and clinical evaluation of a chromogenic endotoxin assay for horses
      with acute intestinal disorders.
AB  - In this study the laboratory and clinical performance of a chromogenic endotoxin
      assay for equine plasma was evaluated. The assay was sensitive (detection limit 3
      ng LPS/L plasma), reproducible (within and between-assay CV at 50 ng LPS/L E.
      coli O111:B4 LPS standard addition was 5% and 7.5%, respectively), and not
      substantially affected by enhancement or inhibition phenomena (recovery of an in
      vitro spike was 75-125% in 80% of the samples). LPS added to whole blood was
      rapidly inactivated upon incubation at 37 degrees C but not at 0 degrees C. A
      recently developed blood collection tube for LPS testing was found suitable, i.e.
      LPS-free and providing non-contaminated samples. In 48 horses suffering from
      acute abdominal diseases requiring surgical treatment, LPS levels were
      significantly higher in platelet-rich plasma (PRP) than in platelet-poor plasma
      (PPP), and the proportional difference was related to the PRP platelet count (r =
      0.52, p < 0.001, mean difference 48%, range 8-77%). LPS levels were also
      significantly higher in horses that died or were euthanized than in surviving
      horses (mean 16.5 and 7.1 ng/L PRP, respectively, p < 0.05). We conclude that LPS
      can be measured in equine plasma with picogram sensitivity and recommend the use
      of PRP instead of PPP for clinical LPS testing. For clinical use a decision limit
      for endotoxaemia of 5 ng LPS/L PRP appeared to be inadequate. Analysis at a
      higher cut-off level for endotoxaemia and the evaluation of clinical,
      pathological, and laboratory parameters would be more meaningful.

PMID- 7801504
TI  - Intravenous anaesthesia in horses by guaiphenesin-ketamine-detomidine infusion:
      some effects.
AB  - The effects of total intravenous anaesthesia with an intravenous infusion of a
      combination of guaiphenesin, ketamine and detomidine were studied in 10 patients
      scheduled for elective surgery. Anaesthesia was maintained by the infusion of
      guaiphenesin (100 mg/ml), ketamine (2 mg/ml) and detomidine (0.02 mg/ml). The
      infusion rate was 1 ml/kg/hr. During anaesthesia, pulse rate and mean arterial
      blood pressure were continuously recorded. Arterial blood gases and pH were
      determined immediately after induction and at stated times during anaesthesia.
      Venous blood was sampled to determine plasma glucose, lactate, lactate
      dehydrogenase (LDH), creatine phosphokinase (CPK) and aspartate aminotransferase
      (AST) concentrations. Values were compared with those determined in blood sampled
      before the premedication. All determined parameters with the exception of the
      plasma glucose concentration, the arterial oxygen tension and the AST
      concentration did not change significantly and remained within normal ranges. The
      plasma glucose concentration increased significantly after the induction of
      anaesthesia compared to the control value but decreased to normal values during
      anaesthesia. The arterial oxygen tension was on average 30% lower than normally
      wished. Compared to the control value the plasma concentration of AST was
      significantly decreased at the end of anaesthesia. Based upon the results of this
      study an infusion of guaiphenesin, ketamine and detomidine appears to be useful
      for the maintenance of total anaesthesia in horses.

PMID- 7801505
TI  - Nerve supply of the proximal sesamoid bone in the horse.
AB  - In chronical proximal sesamoid bone lameness it is difficult to localise the
      exact site of pain. A specific diagnostic analgesia is not available because of a
      deficiency of detailed information about the nerve supply to the proximal
      sesamoid bones and surrounding area. A macroscopic study of the nerve
      distribution to the proximal sesamoid bones of 10 foals and 5 adult horses
      revealed that these bones are innervated by two branches, in this study called
      the medial and lateral sesamoidean nerve, respectively, originating from the
      medial and lateral palmar nerve. Histology of the left forelimbs of two fetuses
      and one foal confirmed the macroscopic findings. Additionally, histology of ten
      proximal sesamoid bones of adult horses showed that myelinated nerve fibres are
      present in the nutrient foramina and in the trabecular bone, accompanying the
      larger arteries. This study provides possibilities for future diagnostics of
      proximal sesamoid bone lameness by specific local perineural analgesia.

PMID- 7801506
TI  - Clinical and force plate evaluation of the effect of a high plantar nerve block
      in lameness caused by induced mid-metatarsal tendinitis.
AB  - To answer the question whether it is possible to differentiate, by means of a
      high plantar nerve block in the hind limb, flexor tendon lameness from a
      suspensory ligament lameness, mid-plantar tendinitis or desmitis was induced with
      collagenase in five Standardbred horses in two trials. Before the induction of
      lameness, and on the fourth (D4) and fourteenth day (D14) after the induction of
      lameness the horses were evaluated subjectively (clinical lameness score),
      objectively (ground reaction force (GRF) measurements), and ultrasonographically.
      Clinical evaluation and GRF measurements were also done on D4 and D14 after a
      high plantar nerve block. From the GRF measurements variables were selected and
      analysed and related to the clinical lameness score. The horses were
      significantly lame on D4; this lameness had decreased on D14. The clinical
      findings were supported by the GRF data. In the flexor tendon group, a high
      plantar nerve block resulted in soundness or lameness in the other hind limb,
      whereas in the suspensory ligament group the effect was less conclusive. The
      correlation between the subjective clinical lameness score and several
      objectively measured GRF variables proved to be moderate to high. The collagenase
      model proved to be useful to study the effect of a high plantar nerve block on
      lameness resulting from induced tendon/ligament lesion. However, a high plantar
      nerve block cannot be used to differentiate between flexor tendon and suspensory
      ligament lesions.

PMID- 7801507
TI  - Ultrasonographic evaluation and long-term follow-up of flexor tendonitis/desmitis
      in the metacarpal/metatarsal region in Dutch warmblood horses and standardbred
      racehorses.
AB  - Over a 2 year-period, the ultrasonographic localization and distribution of
      flexor tendinous and ligamentous injuries, the long-term follow-up, and the
      outcome were studied in 101 Dutch Warmblood horses (DW) with a mean age of 8.7
      years and in 71 Standardbred racehorses (ST) with a mean age of 5.2 years. The
      ratio between forelimb and hind limb flexor tendonitis/desmitis in the DW-group
      was 4:1 and in the ST-group group 4:3. In the DW-group, tendonitis/desmitis of
      the suspensory ligament (32%), the superficial digital flexor tendon (29%), the
      distal carpal check ligament (17%) of the forelimb (SLf, SDFf, and CL,
      respectively) and the suspensory ligament (11%) of the hind limb (SLh) occurred
      the most often. In the ST-group, tendonitis of the SDFf (34%) and desmitis of the
      SLh (34%) and SLf (18%) were the most common injuries. Of the 60 Dutch Warmblood
      horses available for follow-up, 25% showed full-functional recovery. Of the 61
      Standardbreds available for follow-up, 18% showed full-functional recovery.
      Overall, local axial lesions seemed to have a worse prognosis than local abaxial
      or diffusive lesions.

PMID- 7801508
TI  - The relationship between intra-articular and juxta-articular intraosseous
      pressures in the metatarsophalangeal region of the pony.
AB  - Eight metatarsophalangeal (fetlock) joints were studied in anaesthetized young
      ponies. Pressure measurements were made in the joint and at various sites in the
      marrow cavity of the third metatarsal bone with simultaneous measurement of
      systemic arterial and venous blood pressures. Fetlock joint flexion was always
      associated with a statistically significant initial decrease in intra-articular
      pressure (p < 0.05) followed by a marked increase in pressure (p < 0.05).
      Subsequent extension was accompanied by a similar pressure pattern, although
      there appeared to be a hysteretic relationship. Fetlock joint distension induced
      by incremental injection of saline caused a stepwise increase in the intra
      articular pressure. Both joint flexion and effusion were associated with an
      increased intraosseous pressure within the third metatarsal bone. This effect was
      most pronounced at the distal end of the bone, probably through partial
      obstruction of the vessels draining the epiphysis and metaphysis.

PMID- 7801509
TI  - Kinematics of treadmill versus overground locomotion in horses.
AB  - A kinematic analysis was carried out to compare treadmill and overground
      locomotion in horses at the trot. Stride variables and limb and trunk movements
      of 10 Dutch Warmblood horses were measured using the CODA-3 gait analysis system.
      Overground recordings were made on a rubber ground surface and on an asphalt
      track. Treadmill recordings were taken after a controlled habituation programme
      and at the same velocities as measured overground. On asphalt, a shorthened
      stride duration and a decreased vertical displacement of the withers were found
      compared with those on rubber ground. On the treadmill, stance duration of the
      forelimbs was longer than for either overground condition. Correspondingly, the
      hind limbs were placed earlier than the forelimbs in making diagonal ground
      contact in overground locomotion, but this changed to preceding forelimbs on the
      treadmill. Both forelimbs and hind limbs were moved more caudally during the
      retraction phase on the treadmill, while no differences were found in the
      protraction angle. The vertical movement of the hooves as well as the withers was
      smaller on the treadmill than on rubber ground. Treadmill belt velocity decreased
      by 9% during the stance phase. This is supposed to be an important reason for the
      differences in biomechanics and kinematics between treadmill and overground
      locomotion, which must be kept in mind when data obtained during treadmill
      locomotion have to be extrapolated to overground conditions.

PMID- 7801510
TI  - Kinematic detection of superior gait quality in young trotting warmbloods.
AB  - This study was conducted to identify objective criteria to select young horses
      with a good gait, which is a prerequisite for good performance in adult horses.
      The trot of 24 26-month-old Dutch Warmbloods, led on a loose shank, was
      subjectively scored by a judge and objectively assessed on a treadmill by using
      kinematic analysis equipment. It appeared that forelimb and hind limb stride and
      swing duration, scapula rotation, forelimb maximal fetlock extension, forelimb
      maximal retraction, hind limb maximal protraction, maximal stifle flexion, and
      maximal tarsal flexion significantly correlated with a generally accepted gait
      score in which length, suppleness, and strength are judged. Moreover, the ranking
      of the individual horses on the basis of gait quality according to their
      objectively measured kinematic variables was similar to the subjective ranking
      given by the judge. Thus, a complete picture was obtained of the variables in
      equine locomotion that determine the quality of the trot in warmbloods.

PMID- 7801511
TI  - The effect of toe weights on linear and temporal stride characteristics of
      standardbred trotters.
AB  - Toe weights are applied to influence the stride characteristics of trotters. The
      quantitative effect of 88-g toe weights on the stride characteristics of
      Standardbred trotters was evaluated in a kinematic study using a CODA-3 analysis
      system. Six trotters were studied at a speed of 11 m/s on a treadmill. Temporal
      gait variables, joint angles, and the trajectories of the forelimb hoof were
      calculated. The stride patterns of the individual trotters were assessed by a
      judge and compared to the CODA-output. Those trotters with poor flexion of the
      carpal joint during the swing phase or with insufficient knee action responded
      with better carpal flexion and more knee action when toe weights were attached.
      No effect of toe weights on the protraction of the forelimb could be
      demonstrated. Stride length, stride duration, and the relative duration of the
      stance and swing phase as a percentage of the stride did not respond to toe
      weights. It is concluded that toe weights can be useful in Standardbred trotters,
      but their effect depends on the individual gait pattern.

PMID- 7801512
TI  - Reproduction of proliferative enteritis in hamsters with a pure culture of
      porcine ileal symbiont intracellularis.
AB  - Hamsters, three weeks old, were inoculated orally with suspensions of
      intracellular bacteria, grown in tissue culture cells, IEC-18, rat enterocytes.
      Cells had been infected with suspensions of intracellular bacteria derived from
      the lesions of proliferative haemorrhagic enteropathy occurring naturally in two
      pigs 916/91 and 1482/89. Infected cell lines containing each separate strain,
      916/91 and 1482/89, were passaged one, two or five times and pure cultures of
      intracellular bacteria, identified as ileal symbiont intracellularis by
      immunological means, were collected from the cells and used as inocula. Ten of
      sixteen hamsters dosed with 916/91 passaged one or five times, developed lesions
      of proliferative enteritis evident as necropsy three weeks after inoculation.
      Hamsters inoculated with 1482/89 passaged twice and stored frozen, or IEC-18
      cells alone or those left uninoculated, failed to develop lesions of
      proliferative enteritis. Campylobacter jejuni infection occurred throughout, in
      all groups. Marked hyperplasia of ileal enterocytes, associated with numerous
      intracellular curved bacteria was invariably detected in experimentally affected
      hamsters. Immunofluorescence reactions with specific antibodies indicated that
      these intracellular bacteria were also ileal symbiont intracellularis. The
      results suggested that proliferative enteritis could be reproduced in hamsters
      with a pure culture of an agent derived from pigs. We concluded that the
      reproduction of the disease with our inocula containing a single agent clarifies
      the aetiology of proliferative enteritis in both hamsters and pigs.

PMID- 7801514
TI  - Studies on the factors affecting the hemolytic activity of Fusobacterium
      necrophorum.
AB  - The in vitro activity of the hemolysin of Fusobacterium necrophorum was
      determined using the hemolysis of horse erythrocytes as an assay. The effects of
      medium composition and pH on hemolysin production were investigated. Calf serum
      and casitone stimulated a comparatively higher hemolytic activity in F.
      necrophorum subsp. necrophorum and F. necrophorum subsp. funduliforme,
      respectively. However, sugars, such as glucose, galactose and fructose were
      inhibitors of hemolytic activity. The spectrum of erythrocyte sensitivity to the
      hemolysin indicated that horse and quail erythrocytes were more sensitive to the
      hemolysin of both F. necrophorum subsp. necrophorum and subsp. funduliforme, than
      were cat, dog, rabbit, pigeon and human erythrocytes. Cat erythrocytes were
      however insensitive to the hemolysin of subsp. funduliforme. Cattle, sheep and
      chicken erythrocytes were insensitive to the hemolysin of the two subspecies.
      Medium pH near neutral were more effective in enhancing hemolytic activity, and
      hemolytic activity was positively correlated with growth. In general, F.
      necrophorum subsp. necrophorum was more hemolytic than subsp. funduliforme.

PMID- 7801513
TI  - Comparison of a complement fixation test, a gel diffusion test and two absorbed
      and unabsorbed ELISAs for the diagnosis of paratuberculosis in sheep.
AB  - A complement fixation test for paratuberculosis, a gel diffusion test and two
      enzyme-linked immunosorbent assays (ELISA) were evaluated using sera from
      Mycobacterium paratuberculosis infected and non-infected sheep. Gross pathology
      and histopathology were used as parameters of infection. The two ELISAs, one of
      which is commercially available for testing cattle, were used before and after
      sera had been absorbed with a soluble sonicate of Mycobacterium phlei.
      Differences between the various tests and between ELISAs before and after
      absorption were non-significant (P > 0.05) in non-infected sheep or in animals
      with gross or histopathological lesions. The specificity of all the tests was at
      least 97%. Sensitivity in histopathologically positive sheep was at least 98%.
      Sheep from infected flocks but without histopathological lesions showed
      serological results which were poorly correlated between the various tests.

PMID- 7801515
TI  - The effect of vaccination on the prevalence of paratuberculosis in large dairy
      herds.
AB  - Eight hundred and sixty-six one-month-old female calves were vaccinated using
      heat-killed Mycobacterium paratuberculosis in oil during a five-year period.
      Seven hundred and twenty-one bull calves and 379 female calves served as
      nonvaccinated controls. Two large herds were used in the study. The calves were
      tested by faecal culture and by serologic tests on the day of vaccination, at 3,
      6, 9 and 12 months of age, at breeding and on the day of parturition. The results
      were evaluated by trend analyses. Following vaccination, the faecal shedding of
      bacteria was greatly reduced as determined by annual faecal microscopic tests.
      During the last 6 months of the experiment as few as 9 samples from 612 cattle
      proved positive by microscopy and/or culture. The number of seropositive animals
      and the antibody titres (CFT and AGID) increased during the first three years,
      then declined.

PMID- 7801516
TI  - Brucella abortus cytoplasmic proteins used as antigens in an ELISA potentially
      useful for the diagnosis of canine brucellosis.
AB  - A preparation of Brucella abortus cytoplasmic proteins was depleted of
      lipopolysaccharide (LPS) by immunoadsorption with a monoclonal antibody (BC68)
      specific for the O antigen of B. abortus smooth LPS. This extract was used as
      antigen in an indirect ELISA for measuring antiprotein humoral immune response in
      dogs suffering from brucellosis and in healthy controls. All of the affected dogs
      studied showed IgG antiprotein response, while 2% (2 of 103) of the healthy dogs
      used as controls gave a positive result. All sera found to be positive by ELISA
      were also positive by the rapid slide agglutination test. These preliminary
      results show that the ELISA using B. abortus cytoplasmic proteins could be useful
      for the specific diagnosis of canine brucellosis.

PMID- 7801517
TI  - Sensitive detection of canine parvovirus DNA by the nested polymerase chain
      reaction.
AB  - A polymerase chain reaction (PCR) for the detection of canine parvovirus (CPV)
      was developed. To increase the sensitivity and specificity of the reaction, the
      nested PCR with a double-nested primer pair (inner primer pair) was designed. The
      sequences of the PCR primer pairs were selected from the conserved region in the
      CPV VP1/VP2 gene. The PCR with the outer or inner primer pair alone (single PCR)
      could detect 10 fg of viral replicative form (RF) DNA on agarose gel
      electrophoresis; whereas as little as 100 ag of the RF DNA was detected by the
      nested PCR, which was shown to be 100 times more sensitive than the single PCR.
      Samples prepared from feline panleukopenia virus and mink enteritis virus, both
      having a very close antigenic relationship to CPV, were also amplified by the
      nested PCR. The specificity of the reaction was confirmed by restriction enzyme
      analysis and Southern hybridization. Next, fecal samples were examined by the
      nested PCR. All 10 samples suspected of CPV infection were positive, and two
      restriction sites (HaeIII and HindIII sites) in the PCR product were conserved
      among them. On the other hand, specific amplification was not observed in the
      samples derived from normal dogs. The number of the genome copy in positive
      samples was estimated about 10(9)-10(11)/g by the single PCR and 10(11)-10(13)/g
      by the nested PCR. The assay can be completed in 1-1.5 days, and does not need
      radioisotopes. Thus, the nested PCR seems to be a sensitive, specific and
      practical method for the detection of CPV in fecal samples.

PMID- 7801518
TI  - Application of ELISA to the serological diagnosis of virulent ovine footrot.
AB  - The sensitivity and specificity of an ELISA that detects antibody in the serum of
      sheep against Dichelobacter nodosus was investigated. The sensitivity of the
      assay was determined in two trials in which sheep free of virulent footrot were
      exposed to a virulent strain of D. nodosus. In the first trial up to 96.6% of
      sheep that developed severe foot lesions were seropositive 2 weeks later. The
      proportion of seropositive sheep depended on the interval between exposure to D.
      nodosus and collection of blood samples and reached a maximum 6 weeks after
      exposure in the first trial and plateaued from 8 weeks after exposure in the
      second trial. Of sheep with severe lesions present for only 1 week, 40.0% became
      seropositive, while 98.3% of sheep with severe lesions present for 3 or more
      weeks became seropositive in Trial 1. Of the unexposed control sheep from the
      same flock, 93.3% remained seronegative. At least 75% of sheep that were
      vaccinated with commercial footrot vaccines remained seropositive for at least 24
      months after last vaccination and 58.5% remained seropositive for at least 36
      months. The specificity of the assay in flocks of sheep from different
      geographical regions was determined also. Overall, 95.2% of 2978 sheep free of
      virulent footrot were seronegative. However the rate of false positive
      serological reactions ranged from 1.6% to 11.3% between flocks and was higher in
      older sheep (7.0%) compared with sheep less than 1.5 years old (2.7%). Passively
      acquired colostral antibodies against D. nodosus were measured in 22 lambs and
      did not persist beyond 55 days mean age. Non-specific reactions with cross
      reactive antigens were proposed to explain age related changes in serological
      results. Applications of this ELISA in footrot control programmes are discussed.

PMID- 7801519
TI  - Genomic sequences of bovine papillomaviruses in formalin-fixed sarcoids from
      Australian horses revealed by polymerase chain reaction.
AB  - Seventy six formalin-fixed paraffin-embedded sarcoids from 62 Australian horses,
      collected over a ten year period, were examined for the presence of genomic
      sequences from bovine papillomavirus 1 and 2 (BPV1, BPV2) with the polymerase
      chain reaction (PCR). Sequences that could be amplified by primers specific for
      BPV1 and BPV2 were present in 56 of the 76 sarcoids (73%). A restriction site
      present in BPV1 and absent from BPV2 was detected in 28 of 34 amplified products
      that were treated with endonuclease.

PMID- 7801520
TI  - Influence of dose and route of inoculation on responses of chickens to
      recombinant fowlpox virus vaccines.
AB  - The influence of dose and route of inoculation on responses of chickens to
      vaccination with recombinant fowlpox viruses (rFPVs) expressing an influenza
      haemagglutinin (HA) (FPV-HA) and the infectious bursal disease virus (IBDV) VP2
      antigen (FPV-VP2) has been evaluated. Antibody responses to influenza and fowlpox
      virus were generated following vaccination via the wing web by subcutaneous
      inoculation or skin scarification. Intranasal and conjunctival inoculation failed
      to induce antibodies to FPV or influenza. Following direct intratracheal
      inoculation antibodies developed to influenza but not FPV. Dose response studies
      with the FPV-HA and FPV-VP2 recombinants showed that good responses to FPV and
      the vaccine antigen could be generated over a wide (10000 fold) dose range
      following wing web inoculation. The responses generated by the FPV-VP2
      recombinant over this vaccine dose range protected against IBDV infection of the
      bursae following challenge with the Australian IBDV 002/73 isolate. These data
      suggest that effective application of rFPVs for poultry vaccination may be
      restricted to wing web and parenteral routes of inoculation.

PMID- 7801521
TI  - Experimental colonization of mice with Campylobacter jejuni.
AB  - The ability of one human and two chicken strains of Campylobacter jejuni to
      colonise and survive in three different strains of laboratory mice (NMRI, CBA and
      C57-Black) was studied. Mice were inoculated orally with Campylobacter jejuni and
      faeces samples were cultured at regular intervals during the following months.
      The length of colonisation of mice differed between mouse strains but also
      between Campylobacter strains. The mouse strain C57-Black was not colonised with
      C. jejuni to the same degree as the other mouse strains. It is concluded that
      mice can become colonised for prolonged periods and that they may act as
      reservoirs of Campylobacter for other species.

PMID- 7801522
TI  - Infection of murine fetal brain cell cultures with Listeria monocytogenes.
AB  - The uptake of Listeria monocytogenes by different brain cells was studied in
      primary dissociated brain cell cultures derived from murine fetuses. In respect
      to the supposed intraaxonal migration of Listeria monocytogenes in the
      pathogenesis of listeric focal brain stem encephalitis, it was examined whether
      the bacterium was internalized by neurons. Infection rates of distinct cell types
      were determined by double immunofluorescence with antibodies against cell type
      specific markers and the bacterial pathogen. Because of the changing composition
      of the cultures and time-dependent expression of the oligodendrocyte marker
      galactocerebroside (GC), infections were carried out on day 4, 6, 8, and 15 in
      vitro. Listeria monocytogenes was detected predominantly within macrophages.
      Astrocytes, oligodendrocytes, and fibronectin-expressing cells were infected to a
      lesser extent. The lowest rates of infection were observed in neurons. A tropism
      of Listeria monocytogenes for neurons was not detected in vitro.

PMID- 7801523
TI  - Serotype and genus specific protein antigens of Pasteurella multocida, revealed
      by monoclonal antibodies.
AB  - Two monoclonal antibodies (mAbs) reacting with protein antigens of Pasteurella
      multocida strain M1404 were produced and designated DM-1 and DM-4. DM-1 reacted
      only with the homologous Heddleston serotype 2. On the other hand, DM-4 reacted
      with all the 16 Heddleston serotypes and with other Pasteurella spp., but not
      with any of the other genera tested. Both mAbs may thus be of significance for
      identification and classification. The antibodies could agglutinate P. multocida
      only if the cells were treated with 1N HCl. Neither of the mAbs could opsonise P.
      multocida for phagocytosis by mouse macrophages nor did they protect recipient
      mice against lethal infection. Active immunisation of mice gave rise to only
      partial protection against challenge infection, suggesting a minor role for these
      particular proteins in protection from infection.

PMID- 7801524
TI  - Characterization of antibiotic resistance in Streptococcus suis.
AB  - Twenty one isolates of Streptococcus suis were screened for antibiotic resistance
      by growth on antibiotic-containing media, by measuring minimum inhibitory
      concentrations, by hybridization to specific DNA and oligonucleotide probes for
      antibiotic resistance genes, and by PCR. The isolates were from a slaughter house
      survey of respiratory pathogens in Norwegian pigs in 1986. Fifteen isolates were
      resistant to tetracycline, with MICs ranging from 4-128 micrograms/ml. Genes
      coding for the Tet O and Tet M determinants were detected in eight and five
      isolates, respectively. Genes coding for other Gram positive Tet determinants,
      Tet K, Tet L, and Tet P, were not detected. One isolate was constitutive
      resistant to erythromycin with MIC of 128 micrograms/ml. Five other isolates
      carried inducible erythromycin resistance. All these isolates, and five others,
      were positive in a PCR assay for erythromycin resistance, and hybridized with the
      Erm C and/or Erm B probes. No resistance against chloramphenicol (5
      micrograms/ml) or rifampin (10 micrograms/ml) could be could be detected, but
      five isolates were resistant to streptomycin (250 micrograms/ml), four isolates
      were resistant to kanamycin (10 micrograms/ml), and one isolate was resistant to
      fusicic acid (10 micrograms/ml). In mating experiments with Enterococcus faecalis
      JH2-2 as recipient, tetracycline, erythromycin, and kanamycin genes were
      transferred separately to the recipient strain at a rate of 10(-7)
      transconjugants/recipient cell.

PMID- 7801525
TI  - Emerging chloramphenicol resistance in Staphylococcus lentus from mink following
      chloramphenicol treatment: characterisation of the resistance genes.
AB  - A total of 26 staphylococcal strains isolated from mink with urinary tract
      infections as well as from the environment of the mink were examined for
      antibiotic resistance and prevalence of plasmids mediating resistance to the
      antibiotics applied for prophylactic or therapeutic purposes. Chloramphenicol
      resistance (Cmr) which occurred in fourteen of the eighteen Staphylococcus lentus
      strains, but in none of the Staphylococcus intermedius and Staphylococcus xylosus
      strains, was shown to be mediated by small plasmids of 3.6 to 4.6 kb. On the
      basis of restriction endonuclease mapping and hybridization experiments, four
      different types of Cmr plasmids, designated pSCS14-17, could be distinguished.
      All these plasmids conferred Cmr by encoding the Cm-inactivating enzyme
      chloramphenicol acetyltransferase (CAT). In all four types of Cmr plasmids from
      S. lentus, the expression of the cat gene was inducible with Cm, as demonstrated
      by enzymatic assay and polyacrylamide gel electrophoresis.

PMID- 7801526
TI  - Effect of divalent cations on hemolysin synthesis by Serpulina (Treponema)
      hyodysenteriae: inhibition induced by zinc and copper.
AB  - Serpulina hyodysenteriae produces an oxygen-stable heat-labile hemolysin that may
      be an important virulence factor in the pathogenesis of swine dysentery. We
      examined the effect of Ca2+, Co2+, Cu2+, Fe2+, Mg2+, Mn2+, Ni2+, and Zn2+ on the
      hemolytic activity of cell-free supernatant (CFS) from S. hyodysenteriae, isolate
      B204. Cells harvested from late logarithmic phase cultures were incubated in
      phosphate-buffered saline containing glucose and RNA-core (PBS-GR) with or
      without cations and the hemolytic activity of CFS obtained after successive 30
      min incubation and washing cycles was determined. The addition of either ZnSO4 or
      CuSO4 to the PBS-GR caused complete inhibition of hemolytic activity after 3
      cycles; other cations gave results similar to control extracts. Reduction in the
      concentration of Zn2+ in CFS by 60 to 80% after each incubation cycle and binding
      of Zn2+ by EDTA indicated that Zn2+ was associated with the cell fraction, and
      inhibition of hemolysin activity was specifically mediated by Zn2+. When the
      spirochetes were washed after incubation in the presence of ZnSO4 for 2 cycles
      and incubated in fresh PBS-GR without Zn2+, inhibition of hemolysin activity
      remained unchanged, indicating that the inhibitory effect of ZnSO4 was due to a
      direct action of ZnSO4 on the spirochetes. Since neither the viability of the
      spirochetes nor the activity of pre-formed hemolysin were affected by the
      presence of ZnSO4, the inhibitory effect of Zn2+ cations was attributed to
      reduced biosynthesis by viable S. hyodysenteriae cells rather than interference
      of Zn2+ cations with lysis of erythrocytes by the hemolysin. Transmission
      electron microscopic examination of spirochetes after incubation in PBS-GR
      containing ZnSO4 revealed clumping of ribosomes and clearing of cell cytoplasm.

PMID- 7801528
TI  - Recognition of Leptospira interrogans antigens by vaccinated or infected dogs.
AB  - Antigenic recognition of leptospiral antigens by vaccinated or infected dogs was
      studied by microagglutination test (MAT) and by western blots. In western blots,
      serovar specific antigens detected by MAT migrated in the 18-31 kDa zone. The 25
      31 zone seemed to be linked to antigens indicating virulence of the strain. These
      antigens are LPS. The first antibodies made after infection are produced against
      LPS migrating in the 14 kDa zone. Many protein antigens are common in leptospires
      belonging to different serogroups. Virulent strains exhibited specific antigens
      in the 45 and 32-34 kDa zones.

PMID- 7801527
TI  - Characteristics associated with pathogenicity of avian septicaemic Escherichia
      coli strains.
AB  - Seventeen strains of E. coli, isolated from chickens with colisepticaemia, were
      studied with respect to their pathogenic characteristics including: serum
      resistance, toxin production, pathogenicity for one-day-old chicks, colicin
      production, adherence to and invasiveness of HeLa cells, plasmid DNA profile and
      SDS-PAGE electrophoresis of membrane proteins, as well as electron microscope
      studies and hemagglutination tests for fimbriae. We concluded that the adherence
      to and the invasiveness of HeLa cells were not related to the pathogenicity of
      these strains for chickens. Plasmid profiles were not related to the bactericidal
      activity of the serum. Toxin production was correlated to the highest levels of
      pathogenicity. Some of the strains had mannose-resistant fimbriae. SDS-PAGE of
      membrane proteins of all the strains which were either not pathogenic or which
      had a very high LD50 lacked two major protein subunits of 40.7 kDa and 28.8 kDa
      found only in pathogenic strains.

PMID- 7801529
TI  - Protective effects of serum thymic factor to Leptospira interrogans serovar
      Copenhageni infection in Mongolian gerbils.
AB  - The susceptibility to Leptospira interrogans serovar copenhageni in Mongolian
      gerbils treated with 10 micrograms of serum thymic factor (FTS) 1 day before
      infection was examined. Susceptibility of gerbils treated 5 times with 10
      micrograms of FTS was also investigated. Mortality of FTS-treated gerbils was
      significantly lower than that of controls when small challenge doses were used.
      To analyse the FTS-induced resistance to leptospiral infection, natural killer
      (NK) cell activity and macrophage activity were studied. Macrophage activity was
      unaltered but NK cell activity was enhanced in FTS-treated gerbils, with or
      without leptospiral infection. Since no side-effects of FTS were observed, this
      compound should be considered for the treatment of leptospirosis.

PMID- 7801530
TI  - Relationship between active protection in vaccinated buffaloes against
      haemorrhagic septicaemia and passive mouse protection test or serum antibody
      titres.
AB  - The relationship between the standard passive mouse protection test or serum
      antibody titres measured by indirect haemagglutination or enzyme-linked
      immunosorbent assays and active protection in buffaloes immunized with different
      types of haemorrhagic septicaemia bacterins was investigated. Groups of 2-3
      buffaloes were immunized with the bacterins currently in use in Asia, viz., broth
      bacterin (BB), alum precipitated vaccine (APV) and oil adjuvant vaccine (OAV)
      either subcutaneously (BB, APV) or intramuscularly (OAV) and challenged
      subcutaneously with virulent organisms at different periods post-immunization.
      Although the passive mouse protection and indirect haemagglutination tests
      carried out with the pre-challenge sera from vaccinated buffaloes revealed no
      relationship with active protection in buffaloes, a relationship was observed
      between the ELISA antibody titres and protection. In contrast, a dose-response
      relationship was observed between the homologous active and passive mouse
      protection test.

PMID- 7801532
TI  - Streptococcus bovis infections in pigeons: virulence of different serotypes.
AB  - In a first experiment, the relative virulence for pigeons of 5 strains of S.
      bovis was assessed by experimental inoculations. Two S. bovis serotype 1 strains,
      one serotype 2 strain and two serotype 3 strains were examined. One of the
      serotype 1 strains and the serotype 2 strain were isolated from pigeons that died
      from septicaemia. The other strains were isolated from cloaca samples of healthy
      pigeons. For each strain, 10-20 pigeons were intravenously inoculated with 1 x
      10(9) CFU. Morbidity after infection with the serotype 1 and 2 strains varied
      between 75% and 90%. Disease signs included inability to fly, lameness,
      emaciation, production of slimy, green droppings, polyuria and sudden death. In
      groups of pigeons inoculated with the serotype 3 strains, morbidity was 0% and
      6%, respectively. Results demonstrate that serotype 3 strains are less virulent
      for pigeons than serotype 1 and 2 strains. In a second experiment,
      bacteriological and histological examinations were performed on organs of pigeons
      serially killed between 1 and 10 days after experimental inoculation with an S.
      bovis serotype 3 strain of low virulence. Results were compared with results of
      studies carried out with a highly virulent serotype 1 strain. Notwithstanding
      bacterial spread and replication in various organs of inoculated pigeons,
      clinical disease was not observed and histological lesions were scarce and of
      limited extent.

PMID- 7801531
TI  - Bovine neutrophil activation by culture fluid from Pasteurella haemolytica
      serotypes A1 and A11.
AB  - Neutrophil activation has been thought to contribute to the pathogenesis of
      fibrinous pneumonia caused by Pasteurella haemolytica serotype A1. The activation
      of bovine neutrophils by culture fluid from the pathogenic P. haemolytica
      serotype A1 and the non-pathogenic serotype A11 was compared. Logarithmic-phase
      bacteria of each serotype were incubated in RPMI 1640-medium for 3 h at 37
      degrees C. The culture fluid was collected by centrifugation and concentrated by
      ultrafiltration. The concentrated culture fluids were then tested for their
      ability to induce chemotaxis and respiratory burst in bovine neutrophils.
      Chemotactic activity was of similar magnitude in response to both serotypes. An
      early chemiluminescence response occurred at 5 min at 1:100 dilution and a late
      peak at 11 min at 1:500 dilution for serotype A1. The early peak was absent at
      all dilutions tested for serotype A11. Maximal chemiluminescence response was
      observed at 1:25 dilution with serotype A11 while maximal response was seen at
      1:500 dilution with the culture fluid from serotype A1. Superoxide anion release
      was greater in response to culture fluid from A1 than A11 at all dilutions
      tested. Leukotoxin activity was 50-fold higher in culture fluid from serotype A1
      than in culture fluid from serotype A11. In this study, the ability of P.
      haemolytica to attract and activate bovine neutrophils was not restricted to the
      pathogenic serotype A1.

PMID- 7801533
TI  - Transmission of Salmonella typhimurium to swine.
AB  - These studies were designed to determine the rate of transmission and the
      colonization pattern of Salmonella typhimurium in swine. Two experiments were
      conducted. In experiment 1, swine challenged per os with either S. typhimurium
      strain 798T + or strain 798N + were exposed to heterologous feces. Following
      exposure to heterologous strains, heterologous Salmonella were recovered from the
      feces of infected swine within 3 days and from the tonsil and ileum at necropsy.
      Bacterial populations in swine initially challenged with Salmonella remained
      constant. In experiment 2, Salmonella-free swine were commingled with a
      population of pigs that were shedding 2.69 log10 CFU Salmonella/gram feces.
      Salmonella was recovered from pooled fecal samples from the commingled swine on
      day 2 post-exposure to the infected group. Low numbers of Salmonella were
      detected in the ileocolic lymph node, ileum, cecum or spleen of all commingled
      swine throughout the necropsy period. These data provide a means for evaluating
      transmission of Salmonella to a population of swine which may be used to study
      the mechanisms involved in transmission and maintenance of the disease.

PMID- 7801534
TI  - Antigenic characterization of Mycobacterium bovis BCG culture filtrate.
AB  - Mycobacterium bovis BCG culture filtrate, on gelfiltration chromatography
      revealed four prominent regions. Of these 4, region II possessed the highest
      antigenic reactivity by enzyme-linked immunosorbent assay (ELISA) and delayed
      type hypersensitivity (DTH) skin testing in guinea pigs. On anion-exchange
      chromatography, region II was resolved into 5 prominent fractions of which
      fraction II was found to have the highest antigenic reactivity. On sodium
      dodecylsulphate-polyacrylamide gel electrophoresis (SDS-PAGE), M. bovis BCG
      culture filtrate revealed 11 structural polypeptides. Fraction II yielded a
      homogenous polypeptide of 15.3 kDa molecular weight. All fractions cross-reacted
      with various mycobacteria used in this study except a 15.3 kDa polypeptide which
      was specific to M. bovis BCG.

PMID- 7801535
TI  - A species-specific DNA probe for the detection of Mycoplasma agalactiae.
AB  - A 4.5 kb M. agalactiae DNA fragment present in strains from different areas of
      Sardinia was cloned and used to detect M. agalactiae DNA in sheep milk samples by
      dot blot hybridization. The probe recognized only M. agalactiae strains and did
      not cross-hybridize with other mycoplasmas (M. capricolum, M. mycoides subsp.
      capri, M. mycoides subsp. mycoides, M. putrefaciens and M. arginini) or bacteria
      (E. coli, P. hemolytica, S. aureus, S. epidermis, L. casei, S. durans, S. lactis
      and S. thermophilus) which may also be found in sheep milk.

PMID- 7801536
TI  - Nucleic acid hybridization analyses confirm the presence of a hitherto unknown
      morbillivirus in Mediterranean dolphins.
AB  - In 1990 an epidemic caused by a morbillivirus was noticed among Mediterranean
      dolphins. RNA was extracted from the tissues of dolphins and from cell cultures
      infected with a corresponding dolphin morbillivirus isolate. By nucleic acid
      hybridization this RNA was compared to RNA extracted from animal tissue or cell
      cultures infected with canine distemper virus (CDV), phocine distemper virus
      (PDV) or measles virus (MV). The presence of morbillivirus RNA in the dolphin
      tissue was demonstrated. Morbillivirus N, P, M and F gene mRNAs were detected in
      the RNA from dolphin morbillivirus infected cells. These mRNA species seemed to
      be of approximately the same size as the corresponding mRNA species of CDV, PDV
      and MV. The results of the comparison demonstrated that the dolphin morbillivirus
      is genetically different from CDV, PDV and MV. No indication of a close
      relationship between the dolphin isolate and either CDV, PDV or MV was found.

PMID- 7801537
TI  - Lack of cross-protection between vaccinia virus and orf virus in hysterectomy
      procured, barrier-maintained lambs.
AB  - Hysterectomy-procured, barrier maintained lambs were immunised with either of
      virus or vaccinia virus and subsequently challenged with both viruses. Under
      these conditions lambs were protected from challenge with the homologous virus
      but no cross-protection was observed. The feeding of colostrum that contained
      antibodies to orf virus had no effect on the duration of viral lesions.
      Immunoblotting analysis and ELISA of serum samples taken during the course of the
      experiment indicated that the animals mounted antibody responses to both viruses.
      The cross recognition of 3 vaccinia virus antigens by the hyperimmune anti-orf
      virus serum was revealed by immunoblotting.

PMID- 7801538
TI  - Immune responses to superoxide dismutase and synthetic peptides of superoxide
      dismutase in cattle vaccinated with Brucella abortus strain 19 or RB51.
AB  - Antibody and lymph node cell-mediated immune responses to recombinant Brucella
      abortus strain 19 Cu-Zn superoxide dismutase (rSOD) and to three synthetic strain
      19 Cu-Zn SOD peptides were measured during 2 to 12 weeks following vaccination of
      cattle with B. abortus strain 19 or RB51. Cattle vaccinated with strain 19 or
      RB51 did not produce antibody to rSOD and to the SOD peptides. Lymph node cells
      from cattle vaccinated with strain 19, but not with strain RB51, proliferated
      when incubated with either rSOD or one of the three tested SOD peptides
      (GGDNYSDKPEPLGG). These results suggest that neither the strain 19 nor the strain
      RB51 vaccine induces antibody production to SOD and only the strain 19 vaccine
      induces lymph node cell-mediated immune responses to SOD.

PMID- 7801539
TI  - Potency of partially purified malleo-proteins for mallein test in the diagnosis
      of glanders in equines.
AB  - Malleo-proteins from synthetic broth mallein of six strains of Pseudomonas mallei
      were separated by trichloroacetic acid precipitation, ammonium sulfate
      precipitation and Ultrogel AcA 34 gel filtration chromatography. When tested
      comparatively with Dutch PPD mallein as standard on P. mallei-sensitized and
      normal horses all the strains were found to be malleinogenic, trichloroacetic
      acid precipitated proteins were comparable to Dutch PPD mallein in potency and
      innocuity whereas ammonium sulfate-precipitated proteins elicited non-specific
      reactions. Ultrogel AcA 34 chromatographed high molecular weight proteins (MW
      range > 350,000) were having equal or higher potency and without adverse
      reactions and low molecular weight proteins (MW range 120,000-170,000) nearly
      inactive. Ultrogel AcA 34 column fractionation studies revealed that mallein
      activity was associated with high molecular weight proteins and represented a
      purer sensitin than PPD mallein for the purpose of mallein test.

PMID- 7801540
TI  - [Radiological aspects of acute respiratory insufficiency after heart valve
      prosthesis].
AB  - Analysis of the x-ray findings in 156 patients with acute respiratory
      insufficiency (ART) in the immediate periods after implantation of heart valve
      prostheses has shown that various pulmonary complications, such as pulmonary
      edema (in 84% of cases), atelectasis, hypoventilation (5.1%), hemothorax (6.4%),
      pneumothorax (0.6%) were the prerequisites for the development of respiratory
      disorders. Pneumonias were not the primary cause of ART but an additional factor
      for the respiratory disorder progress, for they develop in the presence of
      previous pulmonary changes. The necessity and possibility of establishing the
      pathogenetic mechanism of pulmonary edema (cardiogenic or noncardiogenic one) is
      shown. The authors emphasize the desirability of regular x-ray examinations as a
      supplementary method in monitoring the patients with acute respiratory
      insufficiency.

PMID- 7801541
TI  - [Effectiveness of fluorography in the prevention and diagnosis of pulmonary
      tuberculosis and cancer].
AB  - Annual fluorographic examinations, involving about 80% of adult population,
      helped detect 81.6 +/- 0.6% of patients with pulmonary tuberculosis and 37 +/-
      0.5% of those with pulmonary carcinoma. Unjustified reduction of the number of
      prophylactic phorofluorographies resulted in a reduction of the level of
      diagnosis of these conditions: the share of detected tuberculosis patients
      reduced to 62.3%. The incidence of bacterial discharge in newly detected cases
      increased by 19.7%, the disintegration phase increased by 16%. Decrease of the
      bacillary nucleus parallelled by an almost twofold growth in the number of lethal
      cases of tuberculosis evidence poor detection of the patients. Reduction in the
      number of cases of pulmonary carcinoma detected by prophylactic photofluorography
      resulted in the reduction of operable patients with this condition from 23.5 to
      18%. A retrospective analysis of photofluorograms of newly detected patients with
      destructive tuberculous processes demonstrated the necessity of annual
      photofluorographic check-ups of the adult population aimed at the detection of
      pulmonary tuberculosis. The authors emphasize that the intervals between
      prophylactic check-ups of subjects at risk of developing pulmonary tuberculosis
      should by no means be prolonged.

PMID- 7801542
TI  - [Computed tomography in the diagnosis of infiltrative pulmonary tuberculosis].
AB  - Computer-aided tomography (CAT) was carried out in 67 patients with infiltrative
      pulmonary tuberculosis. Both standard and high-resolution CAT were used to assess
      the lung status. The data were correlated to x-ray findings. Advantages of high
      resolution CAT in the detection of destruction cavities, foci and interstitial
      changes were shown. CAT helps differentiate between the changes in the
      tuberculous infiltrate due to pulmonary tissue caseous necrosis and the perifocal
      reactions presenting as local edema and serous inflammation. CAT is the most
      effective in the differential diagnosis of pulmonary infiltration of unknown
      origin, in specification of the tuberculous process phase, in assessment of the
      type of residual changes, and in planning of surgery.

PMID- 7801543
TI  - [Effectiveness of computed tomography in the diagnosis of otosclerosis].
AB  - Computer-aided tomography (CAT) is the most informative method for imaging the
      morphologic substrate of an otosclerotic process. In otospongiosis the tomograms
      show compact bone demineralization sites to the front of the vestibule fenestra
      (the fenestral form) or round the cochlear osseous capsule (the cochlear form);
      this latter form is better detectable by densitometry. During the stage of
      "mature" inactive otosclerosis the labyrynth fenestra are exposed to partial or
      complete obliteration. Combinations of active and inactive foci in the temporal
      bone pyramid are seen in 38% of cases. CAT helps accurately define the cause of
      stapedoplasty failure: anvil necrosis and the prosthesis subdislocation. CAT
      should be an obligatory diagnostic component in examinations of patients with
      sound conduction abnormalities.

PMID- 7801544
TI  - [Comprehensive radiologic examination in the diagnosis of parotid salivary gland
      diseases].
AB  - Comprehensive x-ray, ultrasonic and radionuclide examinations of 131 patients
      with chronic sialadenitis (n = 50), sialosis (n = 59), sialolithiasis (n = 9),
      autoimmune disorders (n = 6), and bulky processes (n = 7) of the parotid salivary
      glands were carried out. The diagnostic potentialities of each method in every of
      these conditions were analyzed. No correlation between the structural and
      functional disorders of the parotid glands could be traced. A complex of
      radiologic methods is necessary to fully assess the anatomic and functional
      status of the parotid glands. An algorithm of examination in such conditions is
      presented.

PMID- 7801545
TI  - [Clinical and radiologic characteristics of undeveloped lung in children].
AB  - Lung underdevelopment was detected in 60 of the 2487 children aged 1 to 17 with
      the clinical picture of recurrent bronchitis. Seven patients presented with
      aplasia and agenesia of the lung or its part, ten with cystous hypoplasia, eight
      with common hypoplasia, and thirty-five with acquired form of the respiratory
      system underdevelopment. The efficacies of various methods of radiodiagnosis in
      underdevelopment of the vessels, bronchi, and the respiratory sections varied.
      The major signs of hypoplasia were reduced volume and changed transparency of the
      lung, formation of the mediastinal hernias, appearance of ring-shaped shades,
      disordered structure of the bronchi and major vessels, capillary blood stream
      reduction.

PMID- 7801546
TI  - [Radiologic changes of the hand and wrist in young children with hypotrophy and
      perinatal encephalopathy].
AB  - Disordered growth of the bones by length was found in infants with chronic
      disorders of nutrition and perinatal encephalopathy. Roentgenogrammetry helped
      make a more objective assessment of bone changes as against visual methods. The
      authors distinguish the x-ray characteristics most typical of such patients.

PMID- 7801548
TI  - [Basic principles and development of differential radiodiagnosis in emergency
      gastroenterology].

PMID- 7801547
TI  - [Radiodiagnosis in the evaluation of lung dysfunction in bronchial asthma].
AB  - A combined method of x-ray and radiologic examinations of the lungs revealed in
      asthmatics general disorders of the ventilation and perfusion with fine
      functional changes, presenting as local areas of asthmatic hyperinflation,
      anatomically involving separate segments or lobes of the lungs. Capillary
      circulation disorders develop here as well. Local swelling sites are
      characterized by a certain mobility: they may disappear and reappear in different
      lung segments. The functional potentialities of the diaphragm are virtually
      always reduced.

PMID- 7801549
TI  - [Radiodiagnosis of Le Fort type fractures].
AB  - Le Fort's fractures of maxillary bones are referred to grave injuries that
      require an accurate and urgent diagnosis. A total of 70 patients with different
      variants of such fractures were examined. The x-ray examination included
      polypositional roentgenography, linear tomography and panoramic sonography with
      the Sonarc apparatus. The injuries with all signs of Le Fort's fractures of two
      and even three types predominated, asymmetric injuries were rather frequent.
      Panoramic sonography with the patient in a modified position helped specify the
      volume and extension of the injury to the facial bones, but it should be
      supplemented with linear tomography to detect the injuries of the pterygoid
      processes of the major bone of the anterior and posterior walls of the maxillary
      sinuses, of the frontonasal channel opening, of the posterior wall of the frontal
      sinuses and the anterior cranial fossa structures, the detection of injuries of
      the pterygoid processes being the key sign in the differential diagnosis of Le
      Fort fractures.

PMID- 7801550
TI  - [Effectiveness of radiologic evaluation in the diagnosis of acute traumatic
      pancreatitis].
AB  - Comprehensive radiologic examinations, including panoramic roentgenography,
      echography, computer-aided tomography, of 29 patients with acute traumatic
      pancreatitis that resulted from a combined closed injury of the abdomen, have
      demonstrated a high efficacy of computer-aided tomography in the detection of the
      type of changes in the pancreas and the retroperitoneal fat. Echography is
      advisable for cases when pancreas imaging seems to be possible. Radiologic
      findings completely coincided with the intraoperative ones.

PMID- 7801551
TI  - [Characteristics of maxillary sinuses imaging on various orthopantomograms
      (Experimental study)].
AB  - Presents the results of experimental study of image distortions emerging in
      various methods of obtaining panoramic sonograms of the maxillary sinuses. Direct
      panoramic sonograms obtained with the OP-6 Sonarc orthopantomographer were found
      to give the most objective sizes of the intracavitary formations and their sites.
      The bottom of the orbit is detectable only on such sonograms. Inaccurate
      positioning of the head involve image distortions.

PMID- 7801552
TI  - [Automatization of the working place of radiologist].

PMID- 7801553
TI  - [Improvement of radiologic services].

PMID- 7801554
TI  - [Unusual anatomy of hepatic artery].

PMID- 7801555
TI  - [Discography of the lumbar spine].

PMID- 7801556
TI  - [Isolated pulmonary amyloidosis].

PMID- 7801557
TI  - [Radiodiagnosis of acute diffuse disorders of pulmonary blood vessels].
AB  - Thirty-three experiments with dogs and clinical studies in 93 patients on the
      differential x-ray diagnosis of respiratory distress syndrome helped specify the
      x-ray signs of various stages of this condition.

PMID- 7801558
TI  - [X-ray picture of respiratory distress syndrome (shock lung)].
AB  - X-Ray picture of the respiratory distress syndrome (shock lung) in 78 patients
      exposed to high temperature as a result of gas condensate explosion is analyzed.
      X-ray and morphologic findings in these patients are compared to those in 13
      similar patients in whom acute respiratory failure developed because of other
      causes. Morphologic basis of the majority of x-ray signs of acute respiratory
      distress has been investigated. A relationship between respiratory distress
      syndrome development and changes in the heart size has been revealed, which may
      serve the prediction criterion.

PMID- 7801559
TI  - [Classification of suppurative destructive lung diseases].

PMID- 7801560
TI  - [X-ray diagnosis of chronic traumatic lesions of the diaphragm].
AB  - The authors analyze the clinical and x-ray findings in 24 patients with chronic
      traumatic injuries of the diaphragm. The clinical findings did not hint at a
      chronic traumatic injury of the diaphragm. The x-ray method was the principal in
      the diagnosis of the condition. A correct methodologic approach to the
      examination of a patient helped detect a chronic injury to the diaphragm
      virtually in all the cases and the type of the injury could be recognized by
      routine x-ray methods. Indications for the use of invasive methods of
      examinations were defined: pneumoperitoneum and bronchography. Computer-aided
      tomography failed to simplify the diagnosis of the condition in question, and in
      10% of cases it was hardly informative. A scheme for staged x-ray examination of
      the patients has been developed with due consideration for the possible roentgeno
      semiotic variants.

PMID- 7801561
TI  - [Ultrasonic and computerized tomographic examinations in the diagnosis of
      suppurative-inflammatory diseases of organs of the abdominal cavity and
      retroperitoneal space].
AB  - Comprehensive ultrasonic and x-ray computer-aided tomographic (RCAT) examinations
      were carried out in 97 patients with 120 pyo-inflammatory foci in the abdominal
      cavity and retroperitoneal space. On the whole the sensitivity of ultrasonic
      examinations was 68%, that of RCAT 88%. RCAT was superior to ultrasonic
      examinations in the diagnosis of extra-organic (inter-intestinal, subdiaphragm,
      etc.) involvement, pancreonecrosis, and splenic abscesses. The advantages of this
      method were not so evident in the detection of liver and kidney abscesses and of
      gauze postoperative foreign bodies. Potentialities of an ultrasonic method were
      somewhat superior in localization of a pathologic focus in the pancreas in
      differentiation from a common cyst. Ultrasonic examinations should be widely used
      as a primary method and should to a certain measure determine the necessity of
      RCAT use in the diagnosis of pyo-inflammatory diseases of the abdominal cavity
      and retroperitoneal space organs.

PMID- 7801562
TI  - [Radiodiagnosis of postnecrotic complications of caudal pancreatitis].
AB  - The left kidney and pararenal connective tissue were involved in the process in 3
      cases of 5 with caudal pancreatitis complications. A complex of radiodiagnostic
      methods including, besides x-ray examinations, ultrasonic method and computer
      aided tomography, was used to detect the routes of exudate dissemination from the
      caudal portion of the pancreas into cellular spaces. If a destructive or
      interstitial form of chronic pancreatitis is detected, radiation screening of all
      the possible routes of the exudate dissemination (omental sac, left
      subdiaphragmatic space, left pararenal area, and the lateral canal) is
      recommended. Detection of pathologic formation in these areas implies thorough
      examinations of the pancreas making use of x-ray, ultrasonic, and endoscopic
      methods to rule out or confirm pancreatitis.

PMID- 7801563
TI  - [Computerized tomographic arteriography of the liver].
AB  - Thirty-three patients with primary and secondary tumors of the liver were
      examined by computer-tomographic arteriography. Methods of selective
      intraarterial amplification of a computer-tomographic image is presented, as are
      indications for and contraindications against the use of such technique. The
      authors have united on a single working place a computer-aided tomographer
      Somatom DR-2 and a Siremobil device, this essentially simplifying the
      examinations. Selective administration of a contrast agent through a catheter
      into the celiac trunk helped significantly augment the density (200-240 U) of
      liver parenchyma, this permitting the detection of focal liver involvement
      undetectable by standard computer tomography because of a density similar to that
      of liver parenchyma. The method permitted the detection of foci 3-5 mm in
      diameter. On the whole use of computer-tomographic arteriography helped improve
      the diagnosis of focal liver involvement by 27%.

PMID- 7801564
TI  - [Computerized tomographic arteriography].
AB  - It is not always possible to verify with a sufficient degree of confidence
      malignant tumors of the abdominal cavity using computerized tomography (CT) and
      angiography. The paper is concerned with working out and specifying a method of
      CT angiotomography (CTA), based on ia administration (via the celiac trunk, the
      renal arteries) of a contrast medium to increase the informative value of CT
      imaging, followed by scanning. A conclusion has been made after 27 investigations
      that CTA is capable of providing more complete information on the nature of an
      abnormal process than CT (even with i.v. administrations) or angiography.

PMID- 7801565
TI  - [Organizational possibilities of fluorography improvement].

PMID- 7801566
TI  - [Arterial embolization in unresectable cavernous hemangiomas of the liver].
AB  - Seven transcatheter hepatic artery embolizations (HAE) were carried out in 4
      females with unresectable symptomatic cavernous hemangiomas of the liver. An only
      complication occurred (acute cholecystitis), treated conservatively.
      Devascularization of hemangiomas resulted in decrease (3) or disappearance (1) of
      patients' complaints. Three tumors slightly decreased in size while the rest one
      remained unchanged. Partial fibrosis of the tumor was seen in two cases. All the
      patients are alive and well for 1 to 2.2 years after HAE. Such an operation may
      be useful for palliative treatment of unresectable cavernous hemangiomas of the
      liver.

PMID- 7801567
TI  - [Transcutaneous transsplenic catheterization of the splenic vein].
AB  - The authors have developed a method for transcutaneous transsplenic
      catheterization of the portal vein basin and used this method in clinical
      studies. This method permits a higher quality of spot splenoportography,
      selective catheterization and embolization of the gastric veins in bleedings from
      varicose veins of the esophagus in the patients in whom catheterization of the
      portal vein bain via the transcutaneous transhepatic approach is impossible
      because of liver tumors of occlusive stenotic deformation of the portal vein.

PMID- 7801568
TI  - [Magnetic resonance tomography in late sequelae of spinal and spinal cord
      injuries].
AB  - Magnetic-resonance tomography (MRT) helped obtain a high-resolution image
      characterized by high sensitivity in respect of soft tissue contrast
      visualization and providing direct imaging of the spinal cord and its radicles.
      This method is useful in the diagnosis of injuries to the spine and cord. A total
      of 64 patients of both sexes aged 6 to 67 were examined. The primary diagnosis of
      traumatic changes in the spine and cord was confirmed by MRT in only 62% of
      cases. Two groups of patients were singled out: with acute and chronic injuries,
      subdivided into subgroups with and without spinal cord dysfunction. The detected
      changes were divided into extramedullary (traumatic disk hernias, compression of
      the cord or radicles with a dislocated bone fragment, epidural hematoma) and
      intramedullary (edema, hemorrhages, spinal cord disruption); MRT diagnosis of
      intramedullary changes is particularly important, more so in the absence of bone
      injuries. In remote periods after the trauma the clinical picture was determined
      by spinal canal stenosis, cicatricial atrophic and adhesive changes eventually
      blocking the liquor space. Intramedullary changes presented as spinal cord cysts
      or syringomyelia. A classification of the detected changes by the types of
      injuries and their aftereffects is presented in the paper. The authors emphasize
      the desirability of MRT in spinal injuries with signs of cord dysfunction.

PMID- 7801569
TI  - [An accurate formula for assessing the volume of the right ventricular outflow
      tract].
AB  - Practical application of formulae for separate assessment of the volumes of inlet
      and outlet sections of the right ventricle derived previously by the authors has
      shown that the formula for right ventricular outlet section determining it as a
      curved truncated cone with nonparallel bases does not take into account a
      narrowing in the middle third of the outlet portion during the right ventricular
      systole and/or supraventricular crest hypertrophy. In the specified formula right
      ventricular outlet portion volume is determined as a sum of the volumes of two
      truncated cones with a borderline in the middle of the outlet portion long axis.
      The most reliable difference from the main formula was obtained in the control
      group where the borderline of outlet portion division coincided with the area of
      the maximal stenosis of outlet portion stenosis in the systole. In other groups
      (patients with some congenital heart diseases) the maximal stenosis zone is
      located lower. Hence, the specified formula helps reduce the overvaluing of the
      right ventricular outlet portion volume; to make the estimation more accurate,
      the borderline between the cones should be carried out at the site of this
      portion maximal stenosis.

PMID- 7801570
TI  - [Principles of calculating net costs of health services in roentgeno-radiologic
      institutions].
AB  - Present-day changes of the economic status of medical institutions imply their
      transformation from budget clinics into noncommercial self-supporting structures.
      Medical care rendered to the population begins to be regarded as a specific kind
      of merchandise characterized by a cost whose monetary expression is price. A
      great variety of methods for calculating the net cost of medical care is
      explained mainly by various levels of medical service detailed description and
      the number of economic elements of their net cost taken into account, as well as
      by different technologic and organizational potentialities of medical
      institutions for carrying out the estimations. The method suggested by the
      authors, though not yielding scrupulously accurate results, permits estimation of
      the cost of treatment even without computers reflecting at the same time the
      expenditures of any medical institution rather accurately. Use of computers and
      programs will help more accurately estimate the cost of medical care and rapidly
      make the necessary corrections.

PMID- 7801571
TI  - [Possibilities of urethrosinusovaginography in sex determination of children].

PMID- 7801572
TI  - [Bilateral aseptic necrosis of the heads of the first metatarsal bones].

PMID- 7801573
TI  - [A case of giant calculus of the bladder].

PMID- 7801574
TI  - [Role of computerized tomography in stenoses and other diseases of the trachea
      and main bronchi].
AB  - Fifty-one patients with stenosis of the upper portion of the tracheobronchial
      tree of various origins were examined; the sensitivity of computer-aided
      tomography (CAT) in the diagnosis of stenoses of the trachea and the main bronchi
      was found to be 95.83%, specificity 98.31%, and accuracy 93.87%. CAT is superior
      to other methods of investigation (common tomography, tracheobronchoscopy) in the
      detection of changes in the tracheobronchial walls and the tissues adjacent to
      the trachea and the main bronchi. CAT is particularly valuable for the diagnosis
      of the causes of compression stenosis. The method permits specification and
      recognition of the type of involvement in traumatic injuries (6 cases),
      tracheoesophageal fistulae (6 cases), post-tuberculous processes (3 cases). CAT
      examinations are truly valuable in the diagnosis of osteoplastic
      tracheobronchopathy (3 cases), some other rare diseases (tracheobronchomegaly--1
      case, scleroma--1 case, amyloidosis--2 cases). The authors recommend the optimal
      algorithm of examinations of patients with diseases of the upper portions of the
      tracheobronchial tree: roentgenoscopy--roentgenography--CAT--tracheobronchoscopy.

PMID- 7801575
TI  - [Magnetic resonance imaging of brain neoplasms].
AB  - Magnetic resonance (MR) study of the brain using a low-field imager (0.04 T) was
      carried out in 1035 patients with suspected brain tumors which were detected and
      confirmed in 593 cases. The most frequent findings were neuroepithelial tumors,
      meningiomas, hypophyseal adenomas, and various metastatis lesions. MR features of
      various types were analyzed. Low-field MR imaging helps detect tumors even of
      smaller size, localize them, determine their dissemination and the status of the
      adjacent tissues, thus providing (similarly as high- and middle-field MR imaging)
      valuable diagnostic information.

PMID- 7801576
TI  - [Magnetic resonance tomography in oncologic gynecology].
AB  - Magnetic resonance tomography was carried out in 355 patients with gynecologic
      tumors: cancer of the cervix uteri (n = 75), endometrial cancer (n = 75), ovarian
      tumors (n = 205, 102 with benign and 103 with malignant tumors). The diagnosis
      was confirmed by histologic examinations of biopsy specimens or intraoperative
      material in all the cases. To compare the efficacies of various diagnostic
      methods, ultrasonic examinations were carried out in all the 355 patients, and in
      45 of them computer-aided tomography (in 15 patients with cancer of the cervix
      uteri, in 15 with endometrial cancer, and in 15 with ovarian cancer). Magnetic
      resonance tomography helped specify the diagnosis and degree of the process
      dissemination, chose an adequate method of treatment, monitor its course, and
      follow-up the patients after the treatment.

PMID- 7801577
TI  - [Combined radiologic diagnosis of pulmonary edema].

PMID- 7801578
TI  - [Changes in gastric and duodenal mucosa in patients with chronic diffuse liver
      diseases].
AB  - Comprehensive x-ray endoscopic and morphologic examinations of 182 patients with
      chronic diffuse diseases of the liver were carried out to detect changes in
      gastroduodenal mucosa and the incidence of these changes in this patient
      population. Pathologic shifts were revealed in 132 patients (72.6%); various
      morphologic forms of chronic gastritis were found in 67 (39%), erosions in 41
      (23%), gastroduodenal ulcers in 24 (13%) of these. The incidence of the detected
      changes was in direct correlation with the stage of the underlying disease.

PMID- 7801579
TI  - [Bengal rose labeled with short-living cyclotron iodine 123 in the radionuclide
      study of the hepatobiliary system].
AB  - Bengal rose stain labeled with short-lived 123I (123I-BR) was used in diagnostic
      examinations of the hepatobiliary system of 201 patients with various diseases.
      This agent was found superior in many respects to other hepatobiliary compounds.
      Due to an essential reduction of the radiation load of the critical organs use of
      higher activities of 123I-BR becomes possible (120 MBc and higher), this
      permitting an effective study of rapidly coursing hemodynamic processes. A single
      complex radionuclide examination permits obtaining complete information on the
      hepatobiliary system structure and function. The presence of hyperbilirubinemia
      is not a factor reducing the investigation efficacy.

PMID- 7801580
TI  - [Comparative evaluation of diagnostic significance of carbohydrate antigen CA125
      and cancer-embryonal antigen in ovarian cancer].
AB  - Blood CA125 carbohydrate antigen levels were measured in 131 patients with
      malignant, benign, and borderline ovarian diseases. Parallel measurements of
      carcinoembryonic antigen (CEA) were carried out in 101 of them. The diagnosis
      with CA125 measurements was found highly sensitive (96%), specific (77%), and
      accurate (73%). For CEA these values were, respectively, 60, 64, and 24%. Since
      CEA levels in the blood of ovarian cancer patients are not high even in stages
      III-IV condition, correlation between CEA and CA125 levels avsent, and the method
      of CEA measurements inaccurate, we think it unadvisable using CEA as a separate
      marker in diagnostic investigations, more so in monitoring the efficacy of
      treatment of patients with ovarian cancer.

PMID- 7801581
TI  - [Magnetic resonance computerized tomography in the diagnosis of soft tissue
      neoplasms].
AB  - Sixty-three patients with malignant and benign tumors of soft tissues were
      examined making use of magnetic resonance computer-aided tomography (MRT). This
      method was found effective in the diagnosis of soft tissue tumors, permitting the
      detection of tumor connection with the adjacent structures. In some cases MRT
      helped differentiate between malignant and benign soft tissue tumor growth, e.g.
      liposarcoma, malignant fibrous histiocytoma, lipoma, desmoid, hematoma. MRT may
      be effectively used in the diagnosis of soft tissue formations.

PMID- 7801582
TI  - [Radiologic detection of triombrast in liposomes of liver and spleen (first phase
      of clinical trial)].
AB  - Clinical trials of the liposomal form of water-soluble x-ray contrast agent
      triombrast (90 mg of iodine in 1 ml) was carried out in 23 patients with
      Hodgkin's disease, 9 with liver cirrhosis, and 6 with malignant tumors of
      different localizations. Distinct images of the liver and spleen appeared 2-2.5 h
      after intravenous injection of the formulation. They could be observed during 4-6
      h by plane radiography. Liposomal hepatolienography permits identification of the
      structural alteration sites 0.8-1.0 cm in size in these organs. Administration of
      higher doses of the formulation (more that 0.5 ml/kg) was associated with such
      side effects as fever and hyperthermia in 30% of patients parallel with the side
      effects common for iodine-containing x-ray contrast agents. These side effects
      could be eliminated by previous administration of prednisolone and pipolphen.
      These side effects were not observed after injection of lower doses of the
      formulation (less than 0.5 ml/kg) sufficient for an essential improvement of the
      image contrast during computer-aided tomography.

PMID- 7801583
TI  - [Subtotal body irradiation and its effectiveness in the treatment of patients
      with lymphogranulomatosis (first stage of therapy)].
AB  - Total-system radiotherapy in the form of subtotae irradiation of the body was
      administered to 43 primary patients with stages IIB-IVB Hodgkin's disease as the
      first stage of antitumor treatment as an alternative to chemotherapy. An
      immediate stable antitumor effect was observed manifasting by intoxication
      arrest, reduction of the lymph nodes in size and of specific infiltration in the
      lungs, as well as by decrease of red cell sedimentation rate. The mean duration
      of the course was 10.6 days with a 35.0 days interval till the next stage.
      Regularities in the time course of hematologic parameters over the course of
      subtotal irradiation and after it were followed up. Remote (5-year) results of
      treatment of patients with Hodgkin's disease making use of subtotal irradiation
      of the body at the first stage of antitumor therapy compatible to those in
      controls were demonstrated for the first time.

PMID- 7801585
TI  - [75 years since the foundation of the Central Scientific Research Radiological
      Institute].

PMID- 7801584
TI  - [Results of proton therapy in the treatment of pituitary prolactin-secreting
      adenomas].
AB  - The paper presents follow-up results of narrow-beam proton therapy (1000 MeV) in
      75 female patients suffering from prolactin-secreting pituitary adenomas.
      Prolactin concentrations reduced both in macro- and microprolactinomas patients.
      The response was achieved in 96% of the cases in adenoma stages I-IIIa. Such
      results are superior to those reached with other treatment modalities. The
      efficacy of the above proton treatment can be raised by adjuvant use of
      chemotherapy.

PMID- 7801586
TI  - [Results of programmed radiotherapy in patients with inoperable lung cancer].
AB  - Six schemes for therapy of patients with inoperable lung cancer have been
      developed, used in the treatment of more than 300 patients. Static irradiation of
      irregularly-shaped fields was carried out involving into primary irradiation
      volume the primary focus and all sites of regional metastases. The irradiation
      was fractionated; total focal dose (true or equivalent) absorbed from such fields
      was 50 Gy. Local focal dose was up to 60-70 Gy. The total exposure was realized
      as a total radiation exposure or polychemotherapy. A 60% one-year and 15% three
      year survival was attained in treatment of patients with epidermoid
      differentiated cancer (scheme No. 1), this indicating the adeguacy of the chosen
      method for the treatment of this patient population. Strict adherence to
      indications for such therapy when selecting patients for the treatment helped
      attain a positive effect in 90% of patients.

PMID- 7801587
TI  - [Long-term results and perspectives of various radio-endovascular embolization in
      the treatment of patients with renal parenchyma cancer].
AB  - Various types of x-ray endovascular embolization were carried out in 256 patients
      with renal parenchymatous carcinoma over the period of 1979 to 1991. Iodolipol
      chemoembolization with dioxadet, a fat-soluble preparation, significantly
      improved three- and five-year cumulative survival of operable patients to 82.5
      and 77%, respectively, vs. embolization without dioxadet, when only 58% of
      patients survived for three and 51% for five years. In inoperable patients five
      year survival after fatty chemoembolization was 24.5% vs. null in the group
      administered embolization without dioxadet. Ferrochemoembolization appears still
      more promising.

PMID- 7801588
TI  - [Results of modified radiotherapy in the treatment of patients with uterine
      cancer].
AB  - A ten year experience gained in radiotherapy with radio modifiers of 480 patients
      with cancer of the cervix uteri and of 189 ones with endometrial cancer carried
      out at the Central Research Roentgeno-Radiological Institute of the Russian
      Academy of Medical Sciences is analyzed. Local administration of metromidasole
      with dimethysulfoxide essentially enhanced the detrimental effect of radiation on
      the tumor. This is reflected in a higher incidence of local control in
      radiotherapy of patients with cancer of the cervix and corpus uteri. A reduced
      incidence and degree of radiation injury to organs adjacent to the uterus was
      observed.

PMID- 7801589
TI  - [Optimization of obtaining magnetic resonance images in relation to ultra-low
      fields].
AB  - The authors discuss possible approaches to optimization of magnetic resonance
      images in connection with ultralow fields with consideration for external and
      internal factors modifying the contrast. Of the internal factors the crucial role
      is played by protonic density and relaxation time of different tissues; the
      internal factors significant are magnetic induction, characteristics of the
      device and programs, radiofrequency sequence and its parameters, as well as use
      of special contrast agents. Practical measures whose use helps optimize a
      magnetic resonance image, that is, the choice of an adequate pulse sequence, a
      greater number of repetitions, a larger imaging field, a thicker section and its
      better orientation, are described. Standard schemes for obtaining MR images of
      various organs with due account of the before factors with an ultralow field
      tomographer have been developed.

PMID- 7801590
TI  - [Pathogenesis of osteochondrosis].
AB  - Osteochondrosis may present as a separate disease or be one of the stages of a
      dystrophic process coursing in the presence of cartilagenous nodes of deforming
      spondylosis. Primary or secondary dystrophic involvement of the nucleus pulposus
      may eventuate in the disk fibrosis.

PMID- 7801591
TI  - [Comparison of the tolerance of ionic and nonionic contrast media in coronary
      angiography].
AB  - To evaluate the tolerance of ionic versus nonionic CM, a double-blind randomized
      study was performed in 90 pts undergoing cardiac angiography. Nonionic CM caused
      fewer adverse reactions. These were no different in tolerance of two nonionic CM.
      Selective injections of urografin induced significant prolongation of RR, QT, PQ
      intervals on standard ECG of A-H and H-V intervals on intracardiac ECG. Nonionic
      CM induced the minimal electrophysiological disturbances. During left
      ventriculography urografin induced a significant decreased in left ventricular
      systolic pressure, -dp/dt value and increase in both end-diastolic pressure and
      heart rate. Nonionic CM produced less hemodynamics adverse effects. Urografin
      administration produced insignificant increasing of creatinine and urea blood
      levels. Minimal hemodynamics and ECG alterations caused by nonionic CM and low
      risk of complications determine the preferable using of nonionic CM in cardiac
      angiography.

PMID- 7801592
TI  - [Ultrasonic endoscopic examination of the upper portion of the gastrointestinal
      tract].
AB  - Thirty-two patients with various diseases of the esophagus, stomach, and the
      adjacent organs (pancreas, liver and spleen) were examined to assess the
      potentialities of transesophageal ultrasonic endoscopy. The results were compared
      with the findings of fiber gastroscopy, x-ray and ultrasonic transabdominal
      examinations. Nineteen patients were examined for a malignant involvement of the
      esophageal and gastric wall and tumor progress at the site of anastomosis after
      combined treatment of gastric cancer. Ultrasonic endoscopy data were confirmed
      during subsequent surgical interventions and histologic examinations of the
      resected tumors.

PMID- 7801593
TI  - [Possibilities of present-day research methods in the diagnosis of precancerous
      changes in the mucous membrane and "minor" endophytic gastric cancer].
AB  - Complex x-ray, endoscopic and morphologic examinations of the stomach carried out
      in 1250 patients revealed 152 cases with precancer mucosal changes (epithelial
      dysplasia, intestinal metaplasia). X-ray and endoscopic signs are described which
      permit suspect precancer changes in the gastric mucosa and "minor" endophytic
      cancer. Dysplasia progress was observed in 15.5% of cases, no progress in 21.1%.
      The diagnosis of such conditions should be complex. High-risk groups should be
      formed with due consideration for both the morphologic criterion and the x-ray
      and endoscopic signs of gastric wall involvement.

PMID- 7801595
TI  - [Comprehensive clinical and roentgeno-endoscopic examination in the diagnosis of
      tumors of the large intestine].
AB  - A total of 247 patients with diseases of the abdominal organs were examined. 32
      patients with rectal tumors were singled out. The diagnosis of "minor" colorectal
      cancer was particularly difficult. The authors believe that approaches to
      improvement of early diagnosis of colorectal cancer imply definition of roentgeno
      endoscopic signs of rectal wall involvement which will help purposefully and
      timely detect precancer changes in rectal mucosa (dysplasia) as a marker of high
      risk of cancer.

PMID- 7801594
TI  - [Preoperative selective intra-arterial chemotherapy in gastric cancer].
AB  - Preoperative intraarterial chemotherapy was administered to 69 patients with
      gastric cancer. In 34 patients the tumor was localized in the antral portion, in
      27 in the body of the stomach involving the proximal portion, and in 8 total
      involvement of the stomach was revealed. Left gastric artery was catheterized in
      42 patients, right gastric-omental artery in 27. An original method of "loop"
      catheterization of celiac artery branches was used permitting a selective probing
      of gastric arteries proper. For prolonged intraarterial chemotherapy of gastric
      cancer adriablastin or farmorubicin were used in single dose 30 mg/M2, 5
      fluorouracil in dose 500 mg/M2; the cytostatics were infused in 2-3 sessions.
      Immediate results of intraarterial chemotherapy were assessed by angiography and
      other instrumental methods of investigation, as well as intraoperatively and by
      morphometric analysis. In 62.4% of patients significant or total destruction of
      the tumor was attained, the volumic share of a viable tumor component being 0 to
      2.1%. Altogether 95% of patients survived the follow-up of 2 to 30 months.

PMID- 7801596
TI  - [Computerized myelotomography in lesions of the spine and spinal cord].
AB  - CT myelotomography was carried out in 262 patients with various conditions of the
      spine and cord. Pathologic changes were detected in 233 (87.6%) of the examinees.
      The most frequent diseases were tumors and metastases (59 cases), degenerative
      processes, including primary and recurrent hernias (59 cases), atrophic processes
      (46 cases). The accuracy of the diagnosis was found to be 98.6%. A false-positive
      result was obtained in one case with a suspected tumor of the cord. No
      complications were recorded. Computer-aided myelotomography is an effective
      method for the diagnosis of involvement of the spine and cord.

PMID- 7801597
TI  - [Possibilities of radiodiagnosis in systemic connective tissue syndromes].
AB  - Two cases with a rare systemic disease are described. The first of them is as
      follows: a female aged 58 developed sclerodermic cardiomyopathy manifesting by
      cardiomegaly which resulted in myocardial infarction followed by heart aneurysm.
      In the second observation a female aged 60 developed mixed systemic connective
      tissue Sharp-type syndrome though with calcinosis in heart structures (similarly
      as in Thibierge - Weissenbach syndrome) and with renal cysts, possibly of a
      connective-tissue origin. In this latter case the role of ultrasonic examinations
      in the detection of heart and kidney involvement was of particular importance. In
      both cases glucocorticoids were found diagnostically valuable for the detection
      of autoimmune pathologic processes.

PMID- 7801598
TI  - [Diagnostic value of myeloscintigraphy in lesions and diseases of the spine].
AB  - Twenty-seven myeloscintigraphic examinations were carried out in 24 patients aged
      6 to 66 with various diseases and involvements of the spine. Seven patients
      suffered from scoliosis complicated by neurologic symptoms, 2 from compression
      fractures of the L2 vertebra, 1 from a benign tumor of the spinal cord, 13 from
      various dislocations of the upper cervical segments of the spine, and 1 from a
      chronic fracture of the spinous process of C2 vertebra. Myeloscintigraphic
      examinations revealed different disorders of the spinal cord subarachnoidal space
      patency. The findings evidence higher diagnostic potentialities of
      myeloscintigraphy in a number of cases as against x-ray contrast myelography, for
      it permits the detection of patency disorders in the spinal subarachnoidal space,
      undetectable by x-ray contrast myelography.

PMID- 7801599
TI  - A highly purified antithrombin III concentrate prepared from human plasma
      fraction IV-1 by affinity chromatography.
AB  - We describe an improved method for large-scale purification of antithrombin III
      (AT-III) from human plasma involving heparin affinity chromatography of
      redissolved fraction IV-1 paste, viral inactivation by heating, followed by a
      second heparin affinity column. The characteristics of a new heparin affinity
      resin and the ability to extrapolate process behavior from small-scale (20 ml) to
      large-scale (40 liter) columns are described. This supports the use of the small
      scale column for process optimization and validation studies in compliance with
      current regulatory requirements for biological products. The process has been
      characterized by analytical techniques including sodium dodecyl sulfate (SDS),
      reducing SDS, and nondenaturing polyacrylamide gel electrophoresis; laser
      desorption time-of-flight mass spectroscopy, and electrospray mass spectroscopy.
      These results demonstrate that greater than 95% of the protein in the final
      products is AT-III, which is greater than 95% active as defined by thrombin
      inhibition.

PMID- 7801600
TI  - Identification and removal of polymer- and aggregate-forming proteins in human
      plasma albumin preparations.
AB  - The presence of the glycoproteins haptoglobin and hemopexin in human plasma
      albumin (HPA) solutions were demonstrated to be responsible for the formation of
      polymers and aggregates during heat treatment for 10 h at 60 degrees C. Apart
      from haptoglobin and hemopexin three other contaminating proteins were identified
      as transferrin, Gc-globulin and beta 2-glycoprotein. During heat treatment the
      antigenicity of haptoglobin and hemopexin changed markedly and more than 90% of
      the antigens appeared as aggregates in the void volume during the following size
      chromatography. Without loss of albumin haptoglobin and hemopexin were removed
      from the HPA preparation by lectin (concanavalin A) affinity chromatography. The
      haptoglobin- and hemopexin-depleted HPA preparation did not form aggregates or
      polymers during heat treatment.

PMID- 7801601
TI  - Nanofiltration, a new specific virus elimination method applied to high-purity
      factor IX and factor XI concentrates.
AB  - We have validated the use of two new regenerated multilayered structured
      cellulose membranes (BMM), Planova 15 N and Planova 35 N, with respective mean
      pore sizes of 15 and 35 nm, as a new filtration system to eliminate viruses in
      highly purified factor IX and factor XI concentrates. Virus spiking experiments
      indicated that single dead-end filtration on the membranes could remove more than
      5.7-7.8 log10 of human immunodeficiency virus, bovine viral diarrhoea virus,
      porcine pseudorabies virus, reovirus type 3, and simian virus 40, as well as the
      small non-enveloped viruses, poliovirus Sabin type 1 and bovine parvovirus. In
      vitro control tests and animal studies (Wessler stasis model, rat hypotension
      model) of the two concentrates did not reveal any significant differences with
      the non-nanofiltered material. Viral filtration of plasma derivatives on porous
      polymeric membranes might be an essential step in the improvement of their viral
      safety.

PMID- 7801603
TI  - Complement activation during storage of single-donor platelet concentrates.
AB  - Single-donor platelets are stored up to 5 days prior to transfusion. Since
      contact of plasma to plastic surfaces may lead to complement activation, we
      investigated whether there is any increase in the complement factors C3a, C4a and
      C5a in routinely stored single-donor platelet concentrates. C3a levels increased
      about 40-fold during a 7-day storage. C4a levels also increased with storage time
      but to a lesser extent. By contrast, C5a levels remained stable throughout this
      period. ADP- and collagen-induced aggregation was impaired after storage of
      platelets, indicating severe functional injury. In platelet-poor plasma stored
      under identical conditions a comparable increase in C3a and C4a concentrations
      was observed. The loss of platelet function during storage might at least in part
      be due to the excessive anaphylatoxin concentrations observed.

PMID- 7801602
TI  - Studies in red blood cell preservation. 8. Liquid storage of red cells in a
      glycerol-containing additive solution.
AB  - The purpose of the present study was to determine whether a hypotonic additive
      containing a low concentration of glycerol as a membrane permeable solute would
      improve the liquid storage of red blood cells (RBCs). Packed RBCs were stored
      either with 200 ml of an experimental additive solution, EAS 25, containing (mM):
      glycerol 150, adenine 2, glucose 110, mannitol 55, and NaCl 50, or with 100
      ml/unit of a conventional additive solution Adsol. The results show that the
      adenosine triphosphate values, hemolysis, potassium leakage, and the morphology
      scores of RBCs were significantly better with EAS 25 than with Adsol up to 84
      days of storage. The ATP values were significantly different only after the first
      42 days of storage. The mean corpuscular volumes (MCVs) of the RBCs were
      significantly higher throughout in the experimental additive accompanied by
      decreased microvesiculation as compared to Adsol. The total microvesicle membrane
      protein shed by 100 ml of RBCs was 47.92 +/- 12.31 mg in Adsol and 18.96 +/- 5.49
      mg in EAS 25 (p < 0.001). The larger MCVs of the RBCs in EAS 25 may have a
      favorable effect on maintaining membrane integrity by decreasing the loss of
      membrane by microvesiculation.

PMID- 7801604
TI  - Evaluation of apheresis platelet concentrates collected with a reduced (30-ml)
      collection chamber with resuspension and storage in a synthetic medium.
AB  - Recently, the CS-3000 Plus Blood Cell Separator with the TNX-6 platelet
      separation chamber insert has been furnished with a small-volume (30-ml)
      collection chamber. In this study, a platelet synthetic medium containing glucose
      and bicarbonate (PSM) was used for resuspension and storage of this highly
      concentrated platelet product. Eighteen donors participated in a paired study
      design where each participant donated platelets on two occasions, once following
      collection in a standard chamber with resuspension and storage in plasma and once
      following collection in the new chamber with resuspension and storage in PSM.
      Substantially higher total platelet counts were obtained using platelets
      collected in the small chamber and stored in PSM as compared to control (4.4 +/-
      0.9 x 10(11) vs. 3.5 +/- 0.9 x 10(11) platelets, p < 0.01 by paired t test).
      After 5 days of storage, PSM-stored platelets demonstrated higher ATP levels,
      less lactate dehydrogenase in the supernatant and increased lactate production
      with resulting lower pH at day 5 of storage (6.94 +/- 0.15 vs. 7.08 +/- 0.09, p <
      0.05). There were no statistically significant differences of the survival by
      multiple-hit estimation of PSM-stored as compared to plasma-stored platelets as
      determined by 111In labeling and infusion. A slight decrease in the initial
      percent recovery with the additive-suspended as compared to suspended plasma
      cells was noted: 50 +/- 8 versus 54 +/- 9%, respectively (p < 0.05).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7801605
TI  - In vitro platelet function during storage in three different additive solutions.
AB  - Three different synthetic media without glucose were studied for platelet
      storage. The first medium contained acetate and gluconate. The second contained
      acetate, gluconate and citrate. Finally the third contained phosphate and
      mannitol. The purpose of the study was to investigate whether there were
      differences among the various media in terms of preservation of platelet quality.
      Pools of platelet concentrates were prepared from buffy coats. In vitro function
      and metabolic parameters were measured during 5 days of storage in these additive
      solutions as well as in plasma. Platelet aggregation, hypotonic shock response
      and release of beta-thromboglobulin, platelet factor 4 and lactate dehydrogenase
      of the cytosol were equivalent in the media containing acetate compared to plasma
      storage. In vitro platelet functions and pH in these two media were better
      preserved compared to the medium with phosphate and mannitol. In addition
      bacteriological studies using platelets suspended in additive solutions or in
      plasma were carried out. Carryover of 20% of plasma to the synthetic media
      necessary for successful platelet storage in these additive solutions allows
      bacteriological growth. As shown, inoculation of 1 colony/ml Staphylococcus
      epidermidis leads to 10(6)-10(7) organisms/ml after 5 days of storage.

PMID- 7801606
TI  - Effect of agitation on the quality of platelet concentrates.
AB  - Platelet concentrates (PCs) were stored for 4 days at 22 degrees C in 400 ml
      second-generation (PL1240) platelet packs with either constant agitation, manual
      mixing once every 24 h or without agitation at any time. After 4 days storage, in
      vivo recovery, survival and biodistribution were determined following indium-111
      labelling of platelets and infusion into autologous volunteers. In vitro assays
      of platelet function and biochemistry were likewise carried out after 4 days
      storage. The PCs stored without agitation had significantly lower in vivo
      recoveries, pH and aggregation responses to ionophore A23187 and a combination of
      collagen and epinephrine and significantly higher beta-thromboglobulin and indium
      111 release than the agitated PCs. The manually mixed PCs were not significantly
      different from the constantly agitated PCs. PCs mixed simply once every 24 h
      remained viable with active oxidative phosphorylation and a pH above 6.74 in all
      but 1 case indicating that PCs stored at 22 degrees C for up to 4 days with only
      intermittent mixing are satisfactory for transfusion. A change from constant
      agitation would reduce capital costs in mixing equipment and simplify the
      transport of PCs from the transfusion centre to small hospital blood banks.

PMID- 7801607
TI  - Reliable and very sensitive flow-cytometric method for counting low leucocyte
      numbers in platelet concentrates.
AB  - Reduction of leucocytes in blood components, achieved by filtration, may reduce
      the risk of HLA alloimmunization, virus transmission, and febrile reactions.
      Nevertheless, white blood cell (WBC) concentrations obtained in this way can be
      too low to be accurately counted with automated and manual techniques. We
      describe here a rapid, reliable, and very sensitive method for counting low
      leucocyte numbers using flow cytometry. WBC nuclei are labelled by propidium
      iodide. A known amount of fluorescein- and phycoerythrin-conjugated beads
      (Standard Brite, Coulter) is added as an indicator of the examined volume. The
      time required for analyzing one tube is approximately 5 min. This method was
      first validated by comparing WBC counts (120-2,570/microliters) assessed on a
      haemocytometer (Burker) and by flow cytometry. The second step was to determine
      the sensitivity of the method: we diluted normal platelet concentrates with
      phosphate-buffered saline. The comparison of expected with observed values showed
      a very good correlation up to a concentration of 1 WBC/microliter. This technique
      is an accurate method that can be applied in blood bank quality controls and in
      clinical studies.

PMID- 7801608
TI  - Prevalence of infection with the hepatitis C virus among Italian hemophiliacs
      before and after the introduction of virally inactivated clotting factor
      concentrates: a retrospective evaluation.
AB  - In July 1985, all coagulation factor concentrates were withdrawn from the market
      in Italy and replaced with virally inactivated concentrates. A retrospective
      survey comparing the prevalence of the antibody to the hepatitis C virus (anti
      HCV) in hemophiliacs multitransfused with nonvirally inactivated concentrates
      until 1985 with that in previously untreated hemophiliacs transfused exclusively
      with virally inactivated concentrates since 1985 has been conducted in 9 Italian
      hemophilia centers. The centers, which follow about one-fourth of all the Italian
      hemophiliacs, provided information about 708 patients infused for the first time
      before 1985 (group A) and 80 patients infused for the first time between 1985 and
      1991 (group B). The prevalence of anti-HCV was 83% (591/708) in group A and 6%
      (5/80) in group B. For the 5 anti-HCV-seropositive patients from group B, dry
      heating, hydrophobic interaction chromatography plus dry heating (2 patients),
      hot vapor and pasteurization were the virucidal methods used for the concentrates
      implicated in HCV transmission. In the case associated with pasteurization, there
      is the possibility of intrafamilial transmission of HCV. It appears from this
      retrospective analysis that there has been a substantial reduction in the risk of
      HCV transmission since the adoption of virucidal methods. However, these methods
      do not eliminate completely the risk, which might be further reduced by the
      recent adoption of anti-HCV screening for plasma donations used to manufacture
      concentrates.

PMID- 7801609
TI  - High prevalence of HBV infectivity in blood donors detected by the dot blot
      hybridisation assay.
AB  - Hepatitis B virus (HBV) continues to be a significant cause for post-transfusion
      hepatitis in India, in spite of the introduction of compulsory hepatitis B
      surface antigen (HBsAg) screening. To understand the true HBV-infective pool in
      the blood donor population, HBV DNA was detected by a 32P-labelled dot blot
      hybridisation assay in 605 donor units that were negative for HBsAg by a third
      generation Elisa. Serum alanine aminotransferase (ALT) was estimated in all these
      samples and correlated with DNA positivity. The frequency of HBV DNA positivity
      in HBsAg-negative units was very high (9.91%) and correlated well with the
      elevation in ALT (p < 0.00005). However, the frequency of elevated ALT was high
      (11.9%), using the locally determined upper limit of normal, and half of the DNA
      positive samples had a normal ALT. Thus, ALT is a poor surrogate marker for HBV
      infectivity and efforts should be made to apply DNA detection systems in blood
      banks.

PMID- 7801610
TI  - Donor follow-up of influenza vaccine-related multiple viral enzyme immunoassay
      reactivity.
AB  - False-positive enzyme immunoassay (EIA) tests in blood donors receiving influenza
      vaccine were first reported in 1991. We conducted follow-up testing for 6 months
      of those donors with multiply reactive, but unconfirmed EIA (at least 2 positives
      in anti-HCV-1.0, anti-HIV-1, and anti-HTLV-I assays) with a history of recent flu
      vaccine to determine the duration of false positivity. Of 133,000 donors tested,
      16 met study criteria; all 16 were reactive for anti-HCV, 10 were reactive for
      anti-HIV-1, and 12 were reactive for anti-HTLV-I. Fifteen donors were available
      for follow-up testing (using the original screening and supplemental tests): 10
      (67%) reverted to negative for the 3 tests and 5 remained false positive for
      various markers at last sampling (3-6 months after vaccination). The mean
      duration of false positivity for those reverting to negative EIA test status, was
      4.2 months (range 2-7 months) indicating a transient phenomenon and supporting
      studies which suggest a role for IgM in the mechanism.

PMID- 7801612
TI  - Modification of standard Western pretransfusion testing procedures for Taiwan.
AB  - Due to significant differences in blood group antigen and antibody frequencies
      between Taiwanese and Caucasians, standard Western pretransfusion testing
      procedures have been modified for use in Taiwan. Pretransfusion testing consists
      simply of ABO grouping and antibody screening/major cross-matching using the
      manual Polybrene method without any antiglobulin phase. The manual Polybrene
      method is preformed using regents prepared in house and is rapid (about 3 min),
      inexpensive and easy to perform. Rh(D) typing of patients is unnecessary as the
      frequency of D in Taiwanes is 99.67% and the occurrence of anti-D in patients (or
      in haemolytic disease of the newborn) is uncommon. Great reductions in both cost
      and labour have resulted from these modifications, and it is suggested that other
      countries may consider similar modifications.

PMID- 7801611
TI  - High-dose intravenous immunoglobulin in non-ABO transfusion incompatibility.
AB  - The administration of intravenous immunoglobulin (IVIG) in immune and autoimmune
      diseases led us to use this agent to ameliorate or prevent the consequences of
      non-ABO incompatible transfusions in patients who need this form of therapy. IVIG
      (400 mg/kg/day) was infused within 24 h of transfusion in 5 patients with: (1)
      intestinal angiodysplasia, gastrointestinal bleeding, and anti-Kpb; (2)
      paroxysmal nocturnal hemoglobinuria, anti-c, anti E, anti Fyb, anti-K and
      autoantibodies; (3) lymphoma and autoimmune hemolytic anemia (AIHA); (4) systemic
      lupus erythematosus (SLE), AIHA, and anti-D, and (5) SLE and AHIA. A sustained
      increase in hematocrit was noted and no transfusion reaction developed in any of
      the cases. A single dose of pretransfusion IVIG may therefore be a useful
      therapeutic alternative in patients for whom no compatible blood is available.
      Patients with severe anemia, allo- and autoantibodies, either showing hemolysis
      in their pathophysiology or not, cause a serious problem in any transfusion
      center, especially when dealing with emergencies. In order to reduce the risks of
      incompatible transfusions, different modalities have previously been attempted,
      all with poor results. In 1989 we reported the successful use of pretransfusional
      high-dose intravenous immunoglobulin (IVIG) in a patient with gastrointestinal
      bleeding and anti-Kpb. The transfusion of incompatible red blood cells improved
      the anemia and allowed the exploratory laparotomy to take place. A protocol was
      then developed based on this case administering pretransfusion IVIG in high doses
      for patients for whom no compatible blood (non-ABO) is available.

PMID- 7801613
TI  - Sequence analysis of cDNA derived from reticulocyte mRNAs coding for Rh
      polypeptides and demonstration of E/e and C/c polymorphisms.
AB  - RNA derived from enriched reticulocytes of Rh-phenotyped donors was isolated,
      reversely transcribed into cDNA and amplified with Rh-specific primers by
      polymerase chain reaction. Nucleotide sequence analysis of the entire coding
      region of the Rh cDNAs was carried out. Four types of cDNAs were identified,
      tentatively designated as RhSCI, RhSCII, RhSCIII and RhSCIV. Comparison of RhSCII
      with RhSCI (identical to the previously reported RhIXb/30A cDNA), showed single
      base pair difference. Since RhSCI and RhSCII were found to be related to the
      presence of E or e antigen, respectively, the P226A amino acid polymorphism
      appears to be the genetic basis of the E/e polymorphism. RhSCIII was demonstrated
      to be a transcript derived from the RhD gene, with 35 amino acid substitutions as
      compared to RhSCI. RhSCIV was found to be present only in RhC-positive
      individuals, indicating that RhSCIV encodes a polypeptide carrying the C antigen.
      Six nucleotide changes, resulting in four amino acid substitutions W16C, L60I,
      N68S and P103S, were observed between RhSCII and RhSCIV, probably representing
      the C/c polymorphism.

PMID- 7801614
TI  - Evaluation of histo-blood group ABO genotyping in a Danish population: frequency
      of a novel O allele defined as O2.
AB  - Traditional blood group ABO serology is based on immunoreactivity with the
      carbohydrate determinants A, B and H antigens. Recent advances at the DNA level
      of the ABO genes have provided a molecular genetic model for the ABO
      polymorphism. This genetic model has to date only been tested on a limited basis.
      The present study was initiated to evaluate the universality of the proposed
      genetic model on a larger group of serologically defined ABO phenotypes. Three
      hundred healthy Danish blood donors were analysed (A:50, B:50, AB:50, O:150) by
      PCR amplification followed by diagnostic restriction enzyme cutting. In all cases
      A, B, and AB at least one allele of correctly predicted status was found.
      However, in O phenotype individuals, 11 out of 150 carried one allele discordant
      to the proposed genetic model. This novel O allele (3.7% allele frequency) was
      further characterized by diagnostic restriction enzyme analysis in two positions
      divergent between A and B alleles and by DNA sequencing of the two major exons.
      The novel O allele is termed O2 as it typed as B in nucleotide position 526 and
      as A in positions 703, 796, and 803, in contrast to the most predominant O allele
      termed O1, which types as A in all 4 positions. The structural defect in the O2
      allele appears to be an additional substitution at nucleotide position 802. The
      results clearly demonstrate that with the addition of the two distinctly
      different O alleles, O1, O2, the previously proposed molecular genetic basis of
      the ABO polymorphism is quite valid.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7801615
TI  - Anti-j: human cold agglutinins recognizing linear (i) and branched (I) type 2
      chains.
AB  - Two IgM lambda cold agglutinins (CAs) reacted with protease- and sialidase
      resistant antigens expressed in equal strength on human adult (I), newborn (i), i
      adult, rabbit (I) and rhesus monkey (i) erythrocytes. The antibodies were
      inhibited by the linear type 2 sequence lacto-N-neotetraose and the branched type
      2 sequence lacto-N-neohexaose. Endo-beta-galactosidase treatment of red cells,
      which splits type 2 chains from the surface, abolished CA reactivity. The CAs
      expressed the idiotype recognized by the anti-idiotype 9G4 specific for anti-I
      and anti-i CAs. The data suggest that the two CAs recognize linear (i) as well as
      branched (I) type 2 chains. It is proposed to term these CAs anti-j.

PMID- 7801616
TI  - Production of a murine monoclonal antibody to the low-incidence red cell antigen
      Wra: characterisation and comparison with human anti-Wra.
AB  - The production of a monoclonal antibody which detects the low-incidence red cell
      antigen Wra is described. The antibody (BGU1-WR) was isolated following
      immunization of BALB/tk mice with Wr(a+) cells. BGU1-WR is an IgG1 antibody and
      reacted in a manner similar to human polyclonal anti-Wra with untreated, protease
      treated and chemically modified Wr(a+) cells.

PMID- 7801617
TI  - Comparative immunochemical analysis of Wra and Wrb red cell antigens.
AB  - This paper describes immunoblotting and immunoprecipitation studies using
      monoclonal anti-Wra and anti-Wrb antibodies to investigate the nature of the low
      incidence blood group antigen, Wra and its high-incidence allelic antigen Wrb. No
      membrane components were identified by the immunoblotting experiments.
      Immunoprecipitation studies confirmed that the Wrb antigen involves both
      glycophorin A and band 3. The monoclonal anti-Wra, BGU1-WR, failed to
      immunoprecipitate these or any othe red cell membrane component. The significance
      of these findings is discussed.

PMID- 7801618
TI  - A rare leucine 40/arginine40 polymorphism on platelet glycoprotein IIIa is linked
      to the human platelet antigen 1b.
AB  - A rare polymorphism on glycoprotein (GP) IIIa is reported. Sequencing of a 482
      base-pair (bp) PCR product of the genomic DNA of GPIIIa revealed a single-base
      exchange of a G<==>T polymorphism at base 12,569 that created an additional
      restriction site for MspI. This single-point mutation (frequency in Caucasians
      0.00386) is on the HPA-1b gene (HPA-1bvar) and codominantly inherited. The
      exchange of a G for a T results in a leucine-to-arginine substitution at amino
      acid 40 from the NH2 terminus. The binding of anti-HPA-1a and -1b antibodies to
      HPA-1bvar platelets is not influenced.

PMID- 7801619
TI  - Platelet-activating factor in operative salvaged blood.

PMID- 7801620
TI  - Failure of 2nd- and 3rd-generation HCV ELISA and RIBA to detect HCV polymerase
      chain reaction-positive donations.

PMID- 7801621
TI  - Seroreversion in patients with end-stage HIV infection.

PMID- 7801622
TI  - Third-generation HIV-1/HIV-2 ELISA tests.

PMID- 7801623
TI  - HIV-2 infection in a native Dutch blood donor.

PMID- 7801624
TI  - Economic donor screening for anti-HIV in the developing world.

PMID- 7801625
TI  - Uptake of fibrinogen by circulating platelets.

PMID- 7801626
TI  - Anti-HIV rates in blood donations in Europe and the safety of the National Blood
      Supplies.

PMID- 7801627
TI  - Alzheimer's disease: a new hope.
AB  - Until recently, the diagnosis and treatment of Alzheimer's disease was limited.
      This article describes the outcome of new research and advances in the
      pharmacological treatment of this disease, especially the use of Cognex
      (tacrine). It also reports on a multicenter study of tacrine we participated in
      with patients at Raleigh Psychiatric Services, Inc. in Beckley.

PMID- 7801628
TI  - A post-thyroidectomy convulsion: an unusual presentation of chronic
      hypoparathyroidism.
AB  - A 59-year-old woman with previously undiagnosed hypoparathyroidism presented with
      a tonic-clonic seizure 38 years after thyroidectomy. This case is unusual because
      of the initial presentation, but also unique because it is the longest latency
      period between surgery and presentation in recent literature.

PMID- 7801629
TI  - Hantavirus pulmonary syndrome.
AB  - An outbreak of Hantavirus Pulmonary Syndrome (HPS) occurred in the western U.S.
      in 1993. This outbreak was surprising because serious disease due to hantavirus
      had not been reported previously in the U.S., and hantavirus had not been
      documented to cause significant pulmonary disease. Epidemiologic investigation
      discovered a novel strain of hantavirus as the etiologic agent of HPS. The
      Centers for Disease Control (CDC) proposed the name of Muerto Canyon virus for
      this novel hantavirus, which is transmitted through aerosolized excreta of
      infected rodents. HPS begins with a prodrome of fever, myalgia, and respiratory
      symptoms followed by the acute onset of respiratory distress. Since HPS has a
      mortality of 60%, early recognition is important so that supportive treatment can
      be initiated promptly. Intravenous ribavirin is investigational therapy and can
      be obtained through the CDC in Atlanta.

PMID- 7801630
TI  - Politics and medicine.

PMID- 7801632
TI  - Medical assurance: by and for physicians.

PMID- 7801631
TI  - Medical care--a tale of four countries.

PMID- 7801633
TI  - [A new species of Thermoplasma].
AB  - An extremely thermoacidophilic strain, ES-23, was isolated from a self-heating
      coal spoil pile, Sichuan, China. The new isolate grows between 50 and 75 degrees
      C with optimum 70 degrees C and pH 1.0-5.0 with optimum 2.0. Strain ES-23 is
      aerobic and facultative autotrophic depending both heterotrophically on organic
      compounds and autotrophically on elemental sulfur as energy source and CO2 as
      carbon source. G-, spherical or oval with 0.9-1.5 microns in diameter. The
      autotrophic growth showed peri pilus-like structure. Cells Lack a rigid cell wall
      and surrounded only by a single triple layed membrane containing ether lipids. GC
      content of DNA is 38 mol%(Tm). It has been determined as a new species of
      Thermoplasma genus and named Thermoplasma thiooxidans sp. nov.

PMID- 7801634
TI  - [Cloning of T7 lysozyme gene and construction of the vector for transgenic plants
      resistant to bacterial infection].
AB  - DNA were extracted from bacteriophage T7 and digested partially with Ava II. T7
      lysozyme gene was obtained by PCR. DNA sequence analysis showed that the
      nucleotide sequence of T7 lysozyme gene was 99.5% homologous with the reported
      sequence and its deduced amino acid sequence was the same as reported. DNA
      fragment encoding the signal peptide of the pathogenesis-related protein 1b(PR
      1b) from tobacco and cecropin (Shiva-I) gene cloned in pUC19 were modified by
      PCR. The PR-1b signal peptide gene was fused respectively to the 5' terminals of
      T7 lysozyme gene and expression vector, so that T7 lysozyme gene and Shiva-I gene
      could express simultaneously in transgenic plants and the two gene products could
      be secreted to extracellular space.

PMID- 7801635
TI  - [The cloning of threonine operon in vivo and mutagenesis in vitro in E. coli].
AB  - Report here was the selection of the E. coli strain producing 1.2% threonine. The
      wild type threonine operon was cloned in vivo and subcloned in vitro. The
      subclone was mutagenizied in vitro and a clone pTHR12-9-1 producing threonine was
      obtained. Also the effect of pTHR12-9-1 on threonine yield of hosts producing
      different amount of threonine was studied. We found that pTHR12-9-1 could promote
      the production of threonine in lower yield hosts, but it reduced the production
      of threonine in higher yield hosts. The phenomenon was discussed.

PMID- 7801636
TI  - [Cloning and expression of beta-glucosidase gene in Xanthomonas campestris XA5
      5].
AB  - A beta-glucosidase gene from Xanthomonas campestris XA5-5 was cloned in
      Escherichia coli with the broad-host-range plasmid pRK404. The beta-glucosidase
      encoding plasmid designated pLZS1 contained a 1.1kb PstI DNA fragment deriving
      from XA5-5. The plasmid pLZS1 was transconjugated by filter mating into XA5-5
      producing homologous clones XA5-5(pLZS1). Plasmid stability analysis revealed
      that pLZS1 was more stable in XA5-5 than in E. coli JM83. The level of beta
      glucosidase expressed in XA5-5 (pLZS1) was much higher than in E. coli JM83
      (pLZS1) using salicin as the substrate. From the results obtained, it seems that
      the gene product of this cloned DNA fragment has higher affinity to salicin
      substrate, and in some sense reduces the affinity between the enzyme and pNPG
      substrate in XA5-5.

PMID- 7801637
TI  - [Studies on morphological superstructure of inactivated rabies virus and
      uninactivated rabies virus].
AB  - Rabies is widely epidemic in human and animals. It is a very dangerous disease at
      present. In 1919, semple has shown that antigenicity was not destroyed by
      chemicals. After that inactivated rabies vaccine was widely used in human being
      up to more than seventy years. But the afferration of morphological
      superstructure between inactivation and uninactivated, we have not see any report
      on the world.

PMID- 7801638
TI  - [Propagation of the HTV in primary human embryonic kidney and lung cell culture].
AB  - 2 strains of Hantaan virus (HTV, 76-118, Hubei-114) have been propagated
      successfully in cultured primary human embryonic kidney (HEK) and lung (HEL)
      cells. Cytopathic effect (CPE) was observed in the two kind of cells on day 5 to
      7 postinoculation which showed the cell became round and clustered, then
      detached. The replicating peak of the Hubei-114 in two kinds of cell cultures
      appeared on the 11th day and another strain on the 14th or 17th day after
      infection. The ultrastructure changes were observed with EM and IEM, which
      stained by ICGT before embedding. It was discovered that the mitochondia
      atrophied and decreased, and inclusion bodies in the cytoplasma of HEK and KEL
      cells. A large amount of gold granulae were found in the inclusion bodies and the
      virions were seen occasionally. Contamination with other agents have been ruled
      out. Our data suggest that the replicating characters of HTV in these cell
      systems might be possible for the pathogenicity of HFRS for human.

PMID- 7801639
TI  - [Immunologic mechanisms influencing the host-parasite relations in snail
      trematode systems].
AB  - This is a review article based on about 100 papers from leading world newspapers.
      The main features and the way of action of the snail's immune system are
      described. The mechanisms of discrimination between self and non-self are
      presented in detail, including characterization of interacting components of host
      (cellular and humoral factors) and parasite (a sporocyst surface) origin. The
      phenomena of molecular disguise and molecular mimicry are discussed in the
      context of the compatibility between a host and a parasite. The possible ways of
      killing parasite are indicated, with special regard to production of reactive
      oxygen intermediates by hemocytes during the process of killing.

PMID- 7801640
TI  - [Investigations on dynamics of somatic growth in juvenile snails Lymnaea
      stagnalis (Pulmonata: Basommatophora) in conditions of experimental infection
      with parthenites of the trematode Opisthioglyphe ranae (Digenia: Plagiorchiida)].
AB  - The effect of exposure of juvenile individuals of Lymnaea stagnalis to infectious
      eggs of Opisthioglyphe ranae on dynamics of their growth was investigated under
      controlled conditions in laboratory. In infected snails enlargement of body
      weight and linear parameters of shell were observed. Any differences in shell
      shape, analysed on the base of regression of shell width towards to its height,
      were not ascertained in uninfected snails and those infected with parthenites of
      the trematode. The findings with this host-parasite system are discussed in
      relation to possible mechanisms of pathogenesis of somatic gigantism in other
      trematode-snail interactions.

PMID- 7801641
TI  - [Strongyloides stercoralis (Bavay, 1876) Stiles et Hassall, 1902 (Nematoda)-
      intestinal roundworm. II. Geographic distribution (2)].

PMID- 7801642
TI  - [Parasites of mouflons, stags and roe-deer from the Lower Silesia region].
AB  - The study concerning internal and external parasites in deer was conducted in
      selected Lower Silesia forest inspections from May 1988 till June 1992.
      Coproscopic method and section were applied. Only in roe-deer the highly
      extensive invasion of gastrointestinal nematodes was observed (from 50% to 81%,
      depending on inspections). Most frequent were the Ostertagia (60%) and
      Nematodirus (30%) types. Another problem, mainly in mouflons, were lung nematodes
      of Protostrongylidae family, of which the Muellerius capillaris was dominating.
      Of the external parasites, an infection of Lipoptena cervi was discovered in roe
      deer and stag, and Ixodes ricinus appeared most frequently; in Lower Silesia
      appeared the lung nematodes which could be the reason for disease, particularly
      in mouflon. Source of the infection were probably sheep brought to that region
      from Podhale for pasturage.

PMID- 7801643
TI  - [Effect of environmental conditions on parasitic infection of dogs].
AB  - The following intestinal parasites: Dipylidium caninum, Taenia hydatigena,
      Trichocephalus vulpis, Ancylostoma caninum, Uncinaria stenocephala, Toxocara
      canis, Toxascaris leonina, Ascaris sp. have been found on the basis of
      coprological investigations of 120 dogs from the Wroclow shelter, 20 dogs from
      Wroclow flats and 20 dogs from rural area of Kielce district. Total extensity of
      infection of rural dogs was 100% and 40-48% in town. These differences, according
      to the authors, are connected with different breeding conditions as well as with
      the specific contacts of investigated animals with others in various environments
      in Poland.

PMID- 7801644
TI  - [The effect of biotic factors on the eggs of Ascaris spp].
AB  - There are many organisms that influence development and survival of eggs of
      Ascaris sp. Fungi, Acari, Collembola and bacteria are the most important among
      them. They participate mainly in auto-dehelminthisation processes of environment.

PMID- 7801645
TI  - [Anisakis simplex (larva III stage) in stickleback Gasterosteus aculeatus from
      the southern Baltic region].
AB  - One specimen of III larval stage of Anisakis simplex was found in body cavity of
      female stickleback Gasterosteus aculeatus caught in Southern Baltic, in
      Kolobrzeg. In stickleback from Baltic Sea A. simplex was noted for the first
      time. It usually occurs in many other species of fish.

PMID- 7801646
TI  - [Language performance of deaf children and adolescents in verbal and written
      retelling of a picture story].
AB  - Evaluation of the spoken and written language skills of prelingually deaf pupils
      is necessary to improve existing language curricula. Research on written language
      shows notable delays and substantial differences in the development of written
      language in comparison to hearing peers. It is difficult to investigate the
      spontaneous speech because of methodological problems (no control of speech
      parameters, language becomes a confounding variable). The written language is
      therefore a good indicator of language development. Nevertheless, oral
      communication ability can only be studied through spoken utterances. The present
      study deals with oral and writing performance of 23 prelingually deaf pupils from
      9 to 15 years of age whose hearing losses range from 85 to 117 dB. Tape-recorded
      short picture sequences described by the children and adolescents were examined
      by experienced listeners. Furthermore, the written narratives of these picture
      sequences were also analyzed. Parameters included frequency of occurrence of
      content and function words, type-token ratio, mean length of sentence, and speech
      fluency. Speech intelligibility was rated by a panel of naive listeners. The
      results demonstrate the enormous retardation of oral and written language
      development and specific qualitative differences compared to hearing children.
      Language skills improve with age, especially in writing. However, oral and
      written narrative abilities are positively correlated. The loss of sound requires
      substitutional media for the acquisition of a formal language system. This should
      be taken into account in the teaching of language to the deaf in order to build
      up a language competence which is adequate for their age.

PMID- 7801647
TI  - [What is the origin of the frequency effect in absolute judgment? A contribution
      to the theory of judgment].
AB  - The same stimuli receive higher ratings when the distribution in which they
      appear is positively skewed than when it is negatively skewed (frequency effect).
      The effect depends on the number of stimuli (stimulus effect) and the number of
      categories (category effect). The effect may be caused by one of the following
      tendencies: (a) the tendency to assign the same number of stimuli to each
      category (frequency model; Parducci, 1965; Parducci & Perrett, 1972); (b) the
      tendency to exaggerate the difference between the preceding stimulus and the
      present one (contrast model; Haubensak, 1984); and (c) the tendency to assign the
      same categories to the same stimuli (consistency model; Haubensak 1989, 1992a,
      1992b, 1993). The three models are briefly described and evaluated in the light
      of old and new data. The consistency model seems superior to its competitors in
      several respects.

PMID- 7801648
TI  - [Dimensions of similarity of faces--a cross validation].
AB  - Using a series of three experiments, a cross-validation study on the dimensions
      of similarity of faces was carried out. In experiment 1,100 subjects sorted two
      sets of facial photographs (61 men, 62 women; age range 20-60) into groups of
      faces similar in appearance. In experiment 2, a group of 864 subjects rated a
      subset of 36 male and 36 female faces on a personality differential consisting of
      90 scales and a physiognomic differential consisting of 29 scales. Each judge
      rated a single photograph on all scales. In experiment 3, the complementary
      subsets of 25 male and 26 female faces were rated by a third group of 48
      subjects. Each judge rated one set of photographs on eight different scales from
      the personality sphere. Nonmetric multidimensional scaling (ALSCAL) was carried
      out on the similarity judgements obtained in experiment 1. Using multiple
      regression procedures, the ratings from experiment 2 were regressed on the
      coordinates of the similarity spaces. About two-thirds of the personality scales
      and nearly half of the physiognomic scales could be fitted into the three
      dimensional similarity space. By using factor values in place of scale values,
      the Big Five personality factors as well as physical attractiveness and age could
      be fitted into the three-dimensional space. The regression coefficients obtained
      in experiment 2 were used to predict the scale values of the complementary
      subsets of stimulus persons in experiment 3. With the exception of one scale
      ("unlogical--logical"), the cross-validation was extraordinarily successful.

PMID- 7801649
TI  - [Inductive versus associative processes in stimulus discrimination].
AB  - The experiment reported here was an attempt to demonstrate that the solution of
      specific discrimination problems is based on rules rather than on differences in
      associative strengths. With positive and negative patterning as examples, we
      examined whether or not the solution of the discrimination problem depends on the
      number of reinforcements for each individual stimulus when the total number of
      reinforcements is kept constant. This was achieved by manipulating the number of
      stimuli used. We also examined the transfer to new stimuli. Forty subjects took
      part in a 2 x 2-factorial experiment with anticipatory skin conductance responses
      as the dependent variable. All the results were in accordance with the assumption
      of rule based problem solution. The amount of discrimination was independent of
      the number of reinforcements for each stimulus. Furthermore, according to results
      of concept formation studies, an asymmetry in transferring the solution to new
      stimuli was observed.

PMID- 7801650
TI  - [Effects of the median on health cognitions of students].
AB  - Theories about health-related behavior deal with subjective norms and beliefs in
      the susceptibility to specific diseases as determinants of the link between
      attitudes and behavior. Health cognitions are seen as influenced by the salience
      of the targets (see the availability heuristic: Tversky & Kahneman, 1973). This
      study analyzed the effects of mass media reports on health cognitions of young
      people. Nine newspaper articles were created, one for each of three substances
      and the different trends in consumption ("More and more/A lot of/Some ... young
      people take heroin/drink alcohol/smoke cigarettes"). The articles were read by
      191 pupils. Results show that the reading preference and the perceived importance
      of the substances were dominated by the themes of the articles and not by the
      trends in consumption. The acceptance of the consumption of illegal drugs
      increased after the pupils had read articles about heroin. Further, an
      overestimation of the base rates of consumption was observed, especially in
      pupils who smoked. Results are discussed with regard to the importance of
      integrating the impact of mass media into current models of health-related
      intentions.

PMID- 7801651
TI  - [Discrete dynamic systems: the effect of perceptual structuring on composition
      and transfer of knowledge about operating sequences].
AB  - This paper reports two experiments in which we explored the impact of perceptual
      grouping of elements on the organization and use of knowledge about how to
      operate a device. Experiment 1 explored the effects of different perceptual
      display regions on the creation of chunks when sequences of inputs had to be
      reproduced. The effects of regions were not homogeneous, but rather their
      influence depended on interactions between different modalities and learning
      conditions. Experiment 2 investigated the influence of grouping-induced
      composition of knowledge elements on the transfer of sequential knowledge. Two
      different learning criteria were used in the acquisition phase to manipulate the
      degree of composition of knowledge elements. In the transfer phase, subjects
      could transfer (1) the whole sequence of one region, (2) two partial sequences of
      adjacent regions, or (3) single components. It was found that regional invariance
      and immediate succession of components were both important for transfer
      performance. These results suggests that the temporal order of regions is
      important for the organization and use of sequential knowledge, and not the
      grouping of elements by itself.

PMID- 7801652
TI  - [Motor and sensory effects of haptic experiences in implicit and explicit memory
      tests].
AB  - The present experiments explore the components (motor and/or sensory) underlying
      performance in implicit and explicit tests of memory for haptic information. In
      the first experiment, the encoding tasks and the test conditions were varied.
      During the encoding phase half of the subjects were blindfolded and explored real
      objects with their hands in order to answer questions about object properties
      (like form) as fast as possible (active exploration). The other subjects
      performed adequate hand movements without any sensory contact with the objects
      (motor encoding). At testing, for some subjects the active exploration task was
      repeated with old and with new objects. Other subjects who did not perform any
      hand movements based their judgments on sensory impressions only (passive touch).
      The results demonstrate reliable effects of implicit memory for haptic
      information, as revealed by faster reaction times to old than to new objects.
      However, priming effects were only obtained in the active touching test
      condition. This result was observed for both encoding tasks, that is, even for
      subjects who had only performed symbolic hand movements at encoding. Thus, the
      repetition of specific motor processes seems to underly the effects of repetition
      priming in active touch. In the second experiment, a passive touch paradigm was
      realized both at encoding and at test (sensory encoding). The priming effects
      observed under these conditions indicate that sensory processes can be relevant,
      too. Recognition performance was found to be influenced by other variables than
      measures of implicit memory. The results are discussed with respect to process
      oriented and system approaches to implicit memory.

PMID- 7801654
TI  - Improvements in volumetric quantification of circumscribed hepatic lesions by
      three dimensional sonography.
AB  - The size of hepatic tumors is commonly estimated by ultrasound as well as by
      computed tomography by measuring the three diameters followed by computing of the
      volume by applicating the ellipsoid formula. Using the new technique of three
      dimensional-sonography it is possible to perform volume measurement by computer
      linked planimetry. Initial tests with water filled balloons of defined volume
      revealed the accuracy (mean error of 3.0%) and high reproducibility (low intra-
      and inter-observer variance) of the method applied by one investigator
      (intraindividual SD +/- 1.3%) as well as by four different investigators
      (interindividual SD +/- 2.1%). Circumscribed hepatic lesions of 63 patients were
      investigated by using conventional sonography (ellipsoid formula), computed
      tomography (ellipsoid formula) and three-dimensional-sonography (ellipsoid
      formula, ortrip, planimetry). As a volume of reference a mathematical
      approximation for infinite sonographical slices (planimetry) of a very well
      circumscribed hemangioma of the liver was defined. Based on these results a mean
      error of -6% (SD +/- 39%) was determined for conventional sonography. For
      computed tomography a mean error of 2+ (SD +/- 35%) was found, for three
      dimensional-sonography that figure was -6% (SD +/- 5%). Follow up investigations
      can only demonstrate significant alterations of volume when the SD-interval is
      exceeded. Therefore, three-dimensional-sonography provides a more sensitive and
      reliable recognition of volumetric changes of liver tumors than conventional
      sonography or computed tomography does.

PMID- 7801653
TI  - Crypt hyperplasia related to increased lymphocyte activation in the rectal mucosa
      of children with ulcerative colitis.
AB  - The presence of cells positive for interleukin-2 receptors (CD25) and the
      proportion of Ki-67 positive dividing cells in the crypts were studied with
      monoclonal antibodies using sensitive immunohistochemical techniques in the
      rectal biopsy specimens taken from 13 children with inflammatory bowel disease (4
      Crohn's disease and 9 ulcerative colitis) and 10 controls. In all specimens, but
      one, from patients CD25+ cells were found in the surface and crypt epithelium,
      while in none of controls were seen such cells. The mean percentage of dividing
      crypt cells was significantly higher in ulcerative colitis (36.0%) and in Crohn's
      disease (34.6%) than in controls (18.4) (p < 0.001 in both comparisons). In
      ulcerative colitis, a correlation between CD25/CD3 ratios in the surface and
      crypt epithelium and the percentage of dividing crypt cells was found. We
      conclude that activated lymphocytes have a role in the crypt hyperplasia of
      ulcerative colitis.

PMID- 7801655
TI  - [Water melon stomach or antrum gastritis--differential diagnostic aspects].
AB  - The gastric-antral-vascular-ectasia (GAVE), the "Watermelon-stomach", is a
      capillary ectasia of the antrum mucosa. It appears as longitudinal intensive
      redness of the mucosa. This endoscopic picture is caused by fibromuscular
      obliteration of the lamina propria and vascular ectasia with fibrinthromby. The
      pathogenesis of the disease is unknown. Clinical manifestation is chronic blood
      loss with consecutive anaemia. The "Watermelon-stomach" is often not recognized
      and mistaken as "refractory antrumgastritis". Laser-coagulation is a not
      operative therapy of GAVE.

PMID- 7801656
TI  - [Ileus of the small intestine caused by an enterolith].
AB  - Adhesions, tumours and hernias are frequent reasons for an ileus of the small
      intestine in adults. We describe the rare case of an ileus of small intestine
      caused by a big enterolith which was formed in a duodenal diverticulum. As a
      predisposing condition we identified a bone of a chicken.

PMID- 7801657
TI  - [New findings on the mechanism and regulation of intestinal calcium transport].
AB  - Only in the duodenum and in the colon calcium is absorbed by a cellular 1,25
      alpha-Vitamin D3-dependent transport mechanism. Calcium absorption is highest in
      the proximal large intestine, about ten times higher than in the duodenum or in
      the descending colon. 1,25 alpha-Vitamin D3 stimulates calcium transport by
      genomic (slow effect: synthesis of cytosolic calcium binding protein CabP and
      basolateral Ca-ATPase) and non-genomic action (rapid effect: transcaltachyia,
      liponomic effect at the brush border membrane). CabP-dependent translocation
      across the cytosol is thought to be rate limiting step of cellular calcium
      transport. However, only about 50% of calcium absorption is cellular mediated but
      the same amount of calcium convectively is absorbed by transepithelial water flow
      across the paracellular pathway (solvent drag effect). 1,25 alpha-Vitamin D3 not
      only activates cellular calcium absorption but also increases paracellular
      permeability for calcium by an unknown mechanism. However, essential steps in the
      cascade from the interaction of 1,25 alpha-Vitamin D3 with the specific receptor
      over the regulation of the synthesis of calcium binding and transporting proteins
      to the induction of cellular calcium transport are not as yet clearly understood.
      The exact feedback mechanism of synchronized calcium transport across the
      distinct subcellular compartments seems also to be resolved. Cellular calcium
      transport is not found in the jejunum or in the ileum, what can be explained by
      the absence of specific 1,25 alpha-Vitamin D3-dependent carrier systems in these
      segments. On the other hand calcium is secreted across the jejunum and ileum by
      an anomalous solvent drag effect. Hence, intestinal calcium metabolism seems to
      underlie an eneteroenteral circuit: 1,25 alpha-Vitamin D3-controlled cellular
      calcium absorption across the duodenum is followed by paracellular calcium
      secretion across the jejunum and ileum. The carrier in the proximal colon which
      works at the optimal level already under normal nutritional condition could be of
      physiological importance for the reclamation of unabsorbed dietary calcium and
      for the reabsorption of calcium that is secreted across the distal small
      intestine. Under certain pathophysiological conditions, i.e. malabsorption in
      proximal segments or malnutrition, calcium in addition may be conserved by the
      1,25 alpha-Vitamin D3-sensitive carrier in the descending colon.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7801658
TI  - [Structured documentation in gastroscopy: a method for improved quality
      assurance?].
AB  - To further improve quality assurance of gastrointestinal endoscopy, a computer
      assisted documentation system for gastroscopic data was assessed. In this
      context, for the structured written recording system, parameters "expenditure of
      time" and "acceptance by doctors" was evaluated. Contrary to free, unstructured
      data recording, the structured system employing predefined terms was able to
      promote doctors' acceptance of endoscopic terminology standards.

PMID- 7801659
TI  - [Gastric lipase assumes a significant portion of fat digestion].

PMID- 7801660
TI  - [Bacterial translocation in occlusive jaundice].

PMID- 7801661
TI  - [Cor triatriatum sinistrum and atrial septal defect].
AB  - The cor triatriatum sinistrum is a rare congenital malformation. Frequently, the
      patients become symptomatic in infancy with clinical signs of severe congestive
      heart failure. We report on an adult patient with only mild symptoms with cor
      triatriatum sinistrum and atrial septal defect. The embryological basis of the
      disorder and the hemodynamic conditions which permitted this patient to remain
      symptom free for a long period are discussed.

PMID- 7801662
TI  - [Hemitruncus arteriosus in an asymptomatic young man--diagnostic value of
      transesophageal echocardiography].
AB  - The aortic origin of one pulmonary artery, also called hemitruncus arteriosus, is
      a rare congenital anomaly with poor prognosis. In this report the case of an
      asymptomatic 18-year-old man with a systolic precordial murmur and the
      electrocardiographic finding of biventricular hypertrophy is described. The
      diagnosis of hemitruncus was confirmed by cardiac catheterization.
      Echocardiography showed biventricular hypertrophy and moderate enlargement of the
      right atrium and ventricle. In contrast to reports in children, the diagnosis
      could not be verified by transthoracic echocardiography because of the lack of a
      satisfactory acoustic window. On the other hand, the aortic origin of the right
      pulmonary artery and the continuation of the main pulmonary artery as left
      pulmonary artery were visualized by transesophageal echocardiography. However,
      the shunt-volume could not be determined by means of the velocity-time-integral
      and the diameter of the right pulmonary artery because of the turbulent blood
      flow in its proximal part.

PMID- 7801663
TI  - [Effect of a pressure dressing on angiologic complications after diagnostic
      coronary angiography].
AB  - 500 consecutive patients undergoing diagnostic coronary angiography were studied
      for vascular complications using either a conventional (n = 250) or a special
      mechanical device for compression dressing (n = 250). In both groups one case of
      arterial occlusion occurred. Using the conventional pressure dressing, we
      observed four pseudoaneurysms, whereas there were none in the special mechanical
      device dressing group (p < 0.05). In contrast, eight patients developed a deep
      vein thrombosis after mechanical device pressure dressing compared to only 1
      venoust in the conventional dressing group (p < 0.02). Five patients, four of the
      eight patients with mechanical device dressing, suffered from clinical apparent
      pulmonary embolism (p = 0.1801). Thus, a mechanical device pressure dressing may
      decrease the number of arterial pseudoaneurysms but is associated with an
      increased risk of deep vein thrombosis and pulmonary embolism. Therefore, we
      recommend the use of the mechanical device pressure dressing only in selected
      patients with severe obesity.

PMID- 7801664
TI  - [Hemodynamic effects of non-ionic iomeprol 350 and ionic diatrizoate 370 during
      levocardiography and coronary angiography--double-blind randomized comparison of
      2 contrast media].
AB  - A double-blind randomized study was performed in 49 patients to compare the
      hemodynamic changes induced by two contrast agents: non-ionic low osmolar
      lomeprol 350 (IO, n = 25) and ionic high osmolar Diatrizoat 370 (DIA, n = 24). We
      observed significant changes in hemodynamic parameters after laevocardiography
      with DIA: a decrease in LVSP from 125 +/- 14 to 113 +/- 14 mmHg, a decrease in
      mean aortic pressure from 96 +/- 9 to 84 +/- 10 mmHg and in max dp/dt from 2086
      +/- 628 to 1861 +/- 654 mm Hg/sec. LVEDP increased from 13 +/- 5 to 17 +/- 6 mmHg
      and cardiac output from 5.9 +/- 1.2 to 7.7 +/- 1.2 l/min. Heart-rate also rose
      slightly, but insignificant. IO did not alter these parameters. After selective
      coronary angiography both groups did not differ significantly in systolic aortic
      pressure, but DIA caused a drop in diastolic aortic pressure after 10 to 15 sec
      and a bradycardia in the first five sec, in contrast to IO. These effects can be
      explained by a cardiodepressive action of contrast agents on left ventricular
      function, an increase in circulating volume and a reduced peripheral vessel
      resistance. Differences between both agents are probably due to their different
      osmolality. IO is a safe contrast agent, compatible in contrast to DIA. In
      patients with borderline left-ventricular function, IO is preferable, it exerts
      only very slight effects on cardiovascular function.

PMID- 7801665
TI  - [Percutaneous transluminal therapy of local arterial vascular occlusion after
      heart catheterization studies].
AB  - We analyzed the incidence and management of a vascular occlusion at the arterial
      puncture site following diagnostic or interventional cardiac catheterization.
      During the study period 26,245 cardiac catheterization procedures were performed
      for diagnostic (n = 18,895) or interventional (n = 7350) purposes at our
      institution. A total number of 35 arterial occlusions (0.13%) was identified. In
      the early phase of our analysis 14 patients (40%) with peripheral vascular
      obstruction after cardiac catheterization underwent surgical repair. Three
      patients (9%) could be treated conservatively. In 18 patients (51%) acute
      vascular occlusion could be managed by additional intravascular manipulations: 18
      patients underwent successful percutaneous transluminal balloon dilatation, in
      nine patients in combination with intravascular thrombolysis. In three patients
      additional stent-implantation was necessary in the presence of a large occlusive
      dissection. The procedure was primarily successful in 16/18 patients. No
      significant complication occurred. In two patients reocclusion led to operative
      thrombectomy and patch reconstruction in one and to a second catheter-based
      approach in the other patient. Both reinterventions were successful. Thus, in
      experienced hands catheter-based therapy of acute arterial obstruction following
      diagnostic or interventional cardiac catheterization is very effective and should
      be considered as therapy of first choice in these patients.

PMID- 7801666
TI  - [Preliminary clinical comparative study of a new blood pressure instrument with
      wrist cuff].
AB  - The present article reports on the first test results of a new oscillometric
      blood pressure device with a wrist cuff in clinical application. The test was
      performed in two different methodical studies. Both studies included 154
      patients, from which 542 comparative measurements were acquired. The evaluated
      mean differences of systolic and diastolic blood pressures are -for study 1-1.2
      mmHg (standard deviation +/- 7.9 mmHg) and 0.9 mmHg (+/- 6.2 mmHg), for study 2
      1.6 mmHg (+/- 7.4 mmHg) and 3.5 mmHg (+/- 6.7 mmHg) and show a good agreement
      with the method of Riva-Rocci/Korotkoff. The results are discussed in detail and
      conclusions for applicable fields of use for the device and for additional
      clinical studies are drawn.

PMID- 7801667
TI  - [Long-term antihypertensive effect of delayed-action molsidomine].
AB  - The long-term antihypertensive efficacy of molsidomine 8 mg bid was studied in 24
      patients with coronary artery disease in a double-blind, placebo-controlled trial
      of 3 weeks duration. Ambulatory 24-h blood pressure measurements were performed
      at days 1, 2, 7, 14, and 21. Sphygmomanometric measurements of blood pressure
      heart rate and a protocol for number and time of angina pectoris attacks were
      also taken. Following the application of molsidomine a reduction of mean 24-h
      systolic blood pressure of 14% and of mean diastolic blood pressure of 11% was
      observed. The duration of the blood-pressure-lowering action was 7 h. After 3
      weeks of treatment with 8 mg molsidomine sr bid a persistent and significant
      reduction of systolic and diastolic blood pressure was found. A similar acute and
      long-term effect was found by manually measured blood pressures. Heart rate was
      unchanged under molsidomine while the frequency of angina pectoris was
      diminished. In conclusion, a long-lasting antihypertensive efficacy (without
      signs of tolerance) was found over a 3-week period of treatment with 8 mg
      molsidomine in a slow-release formulation given twice a day.

PMID- 7801668
TI  - [The behavior of central and peripheral hemodynamics in isometric and dynamic
      stress in hypertensive patients treatment with regular sauna therapy].
AB  - Effective treatment of hypertension includes decrease of blood pressure at rest,
      dynamic and isometric exercise. Therefore, we investigated the hemodynamic
      changes by radiocardiography (central hemodynamic) and Xenon-133-muscle clearance
      (peripheral hemodynamic) before and after a sauna treatment during a period of 3
      months. 46 hypertensive men (WHO I-II, aged 41 +/- 11 years) participated in the
      study. Systolic and diastolic blood pressure at rest and during dynamic exercise
      were decreased significantly (p < or = 0.01) by sauna therapy. Change of blood
      pressure at isometric exercise was not significant (from 157.5 +/- 16.5 mmHg to
      155.0 +/- 15.4 mmHg). The changes of cardiac output and total peripheral
      resistance were also not significant. Half-time of muscle clearance decreased
      significantly (from 4.4 +/- 1.9 min to 3.2 +/- 1.2 min, p < or = 0.01) and
      functional cross-section A increased significantly (from 3.8 +/- 0.9 mm2.c to 4.4
      +/- 0.9 mm2.c, p < or = 0.01) after the sauna therapy at dynamic exercise, but
      not at isometric exercise. These results show the changes between isometric and
      dynamic exercise, which can only be explained well by a study of peripheral
      hemodynamic. Contrary to dynamic exercise, sauna therapy did not significantly
      decrease blood pressure at isometric exercise.

PMID- 7801669
TI  - [Echocardiographic on-line volumetry using acoustic quantification--comparison
      with manual echocardiographic analysis and cineventriculography].
AB  - Acoustic quantification (AQ) represents an ultrasound imaging system which
      provides detection and tracking of endocardial blood boundaries based on
      quantitative assessment of acoustic properties of tissue in real time. To assess
      on-line quantitation of left ventricular enddiastolic (EDV), endsystolic (ESV)
      volumes and ejection fractions (EF) AQ measurements were compared with off-line
      measurements obtained by manual analysis of video-taped images (MAN) and with
      cineventriculographic data (CV). Calculations by the AQ system were based on an
      algorithm using the monoplane disc method. One day before undergoing CV, 88
      unselected patients were studied with echocardiography in the apical four-chamber
      view. Seventy (79.5%) patients could be studied by AQ. The regression equations
      for determination of EDV were y = 0.7x + 25.2; r = 0.87 (AQ vs. MAN) and y = 0.5x
      + 22.8; r = 0.80 (AQ vs. CV), for determination of ESV they were y = 0.8x + 11.4;
      r = 0.78 (AQ vs. MAN) and y = 0.7x + 6.9; r = 0.71 (AQ vs. CV), and for
      determination of EF they were y = 0.7x + 9.5; r = 0.77 (AQ vs. MAN) and y = 0.6x
      + 15.0; r = 0.71 (AQ vs. CV). Calculations of left ventricular volumes by AQ or
      MAN led to a systematic underestimation, compared to CV. EF was also
      underestimated by AQ, whereas no significant difference between the mean values
      of MAN and CV exists. In a heterogenous population, acoustic quantification based
      on quantitative assessment of tissue acoustic properties mostly permits on-line
      quantitation of left ventricular volumes and ejection fractions in real-time.

PMID- 7801670
TI  - [Comparison of conventional and miniaturized biplane echoscope: initial clinical
      results].
AB  - A subset of patients experiences substantial discomfort on examination with
      transesophageal echocardiography using the conventional echoscope, whereby the
      dimensions of the probe play a decisive role. Miniaturized biplane transducers
      have recently become available (2 x 32 crystals; dimensions 9.5 x 8.7 mm;
      circumference approx. 30% less than the conventional echoscope), which allow
      ultrasound examination at 3.5, 5.0 and 7.0 MHz. A prospective study was carried
      out in 70 patients to compare difficulties on insertion of the probe, subjective
      evaluation by the patient during examination, and the 2D-image as well as Doppler
      and color-coded Doppler quality of the miniaturized biplane echoscope. In 43
      patients, intubation of the esophagus proved less difficult with the smaller
      instrument, it was more difficult in 8 cases. 54 patients reported that the
      discomfort was definitely easier to bear on use of the narrow instrument.
      Concomitant parasympathicolytic medication was needed with the smaller probe in 4
      cases, and 11 times with the conventional echoscope. The quality of the 2D-image
      attained by the miniaturized probe was naturally lower. Employing multi-Hertz
      technology at a frequency of 7 MHz, however, imaging of the anatomy was excellent
      in the near field of 5-6 cm, and nearly equivalent to that of the conventional
      probe (5 MHz). The quality of PW-and CW-Doppler as well as color-coded Doppler
      information was identical. Whenever examination with a conventional echoscope
      promises to be difficult, or when sedation is contraindicated due to a severe
      illness or respiratory insufficiency, transesophageal echocardiography should be
      considered with a smaller biplane probe at higher frequencies.

PMID- 7801671
TI  - [Color Doppler echocardiographic diagnosis in generalized arteriosystemic
      coronary fistulae].
AB  - A 60-year-old woman was referred because of retrosternal pain. Transthoracic
      color-coded Doppler echocardiography showed, in the apical region of the left
      ventricle, multiple connections between the epicardium and the left ventricular
      chamber. The finding was concordant with a generalized arteriosystemic coronary
      artery fistula. Coronarography afterwards with injection of dye into left and
      right coronary arteries resulted in an intense homogenous opacification of the
      ventricle through multiple small coronary artery fistulas. This case report
      represents the first description of color-coded Doppler echocardiography in the
      diagnosis of generalized arteriosystemic coronary artery fistulas.

PMID- 7801673
TI  - [Magnetic resonance tomography--images of inner organs without roentgen rays].

PMID- 7801674
TI  - [Computerized tomography--physical examination in thin layers].

PMID- 7801675
TI  - [Digitalized roentgen department--always correctly exposed images with
      photographic plate technique].

PMID- 7801672
TI  - [Recommendation for the introduction of the International Normalized Ratio as an
      objective measure for the dosage of oral anticoagulant therapy].

PMID- 7801677
TI  - [Ultrasound in pregnancy makes decisions safer].

PMID- 7801676
TI  - [Ultrasound--echo sound in person's body provides information at low cost].

PMID- 7801678
TI  - [No missed dislocation with ultrasound screening].

PMID- 7801679
TI  - [Treatment of Parkinsonism--apomorphine increases therapeutic arsenal].

PMID- 7801680
TI  - [Parliament says no to conscience clause].

PMID- 7801681
TI  - [Many questions remain on new pensions].

PMID- 7801682
TI  - [Nurses and physicians have a common viewpoint of ethics].

PMID- 7801683
TI  - [Nurses cannot perform healing procedures in their professional practice].

PMID- 7801684
TI  - [Worse care when one saves and pushes].

PMID- 7801685
TI  - [Sahlgren reduces in spite of overcrowding].

PMID- 7801686
TI  - [Roentgen nurse halfway between technology and care].

PMID- 7801687
TI  - [Solidarity also concerns the unemployed].

PMID- 7801688
TI  - [Your body language reveals you!. Interview by Pia Carson].

PMID- 7801689
TI  - [We learned our service in the laboratory].

PMID- 7801690
TI  - [In Stenungsund priorities do not disappear when funds break down].

PMID- 7801692
TI  - [New proposal gives employers more power].

PMID- 7801691
TI  - [Elections are over--now professional activities will change].

PMID- 7801693
TI  - [Voluntary workers enrich nursing].

PMID- 7801694
TI  - [Voluntary work prevalent everywhere].

PMID- 7801695
TI  - [Full speed ahead to EC activities in the association. Interview by Carina
      Roxstrom].

PMID- 7801696
TI  - ["Now we accomplish what we struggled for"].

PMID- 7801698
TI  - [We contribute to public health].

PMID- 7801697
TI  - [Jonkoping bets on continuing education].

PMID- 7801699
TI  - [Is this some idea to become a nurse?. Interview by Tomas Nilsson].

PMID- 7801700
TI  - [Women's network is a threat against authority. Interview by Maria Ejd].

PMID- 7801701
TI  - [5000 expect to visit the first fair in Umea].

PMID- 7801702
TI  - [Neuroendocrinological aspects of aging].
AB  - Aging is accompanied by important changes in the production and secretion of
      hormones. These partly arise from changes in the peripheral endocrine glands
      themselves but are also partly the consequence of changes in the neuro-endocrine
      regulating centers of the hormone secretion. Considering e.g. the male gonads, we
      know that the reduced androgen secretion (and the diminished spermatogenesis)
      along the ageing process is the consequence of changes in the testes, such as the
      reduced number of Leydig- and Sertoli-cells, as well as a reduced testicular
      blood-perfusion. But on the other hand, it should also be partly ascribed to
      functional changes of the hypothalamohypophysis. This appears from the lowered
      circadian rhythms of the testosterone levels, the lower plasma levels of free
      testosterone, although the secretion capacity of the Leydig-cells and the
      gonadotrophs is maintained. This points to a lower feed-back set-point of the
      gonadostat. Moreover the amplitude of the LH impulses and the lower opioid tonus
      are decreased in elderly men. In aged people, the secretion of the adrenal cortex
      is essentially characterized by an age-related drop of the androgen secretion
      (DHEAS) and a lower androgens-response to ACTH. This demonstrates changes in the
      adrenal gland itself. On the other hand, the secretion of cortisol and the
      production rates of this hormone remain rather stable, although the feedback
      centre is less sensitive in old lab-animals. This is suggested by a longer
      lasting and higher cortisol secretion after stress. According to Sapolsky, this
      is the consequence of a drop in the number of corticoid receptors in the
      hippocampus, following a loss of neurons, which would be the result of repeated
      stress. This progressive deterioration of the feed-back locus by the final
      hormone is also called: "neurohumoral hysteresis". Signs of its existence in aged
      people can only be found in pathological cases, such as depression or Alzheimer's
      disease. The secretion of growth hormone, and its plasma levels, as well as their
      response to "Growth hormone releasing hormone" (GHRH) is severely reduced in old
      people. This does not appear to be the consequence of the decreased number of
      somatotropic cells in aged people but seems to be caused by an increased
      somatostatin secretion by the hypothalamus. It means that this reduced growth
      hormone secretion has mainly a central origin.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7801703
TI  - [Plague in Zaire].
AB  - Two endemic foci of plague have been discovered in Zaire, the first in the Ituri
      in 1928, the other in North-Kivu in 1938. They are situated in the region of the
      great East-African Rift and are adjacent to the Ugandan focus, identified in
      1877. A strict surveillance of these endemic foci makes it possible to state
      that, between 1928 and 1959, 632 cases of plague have been diagnosed in the
      Ituri, or 20 a year, and 190 in the N-Kivu, or 8 a year. Since then several flare
      ups have been notified. This situation is very remote from the "black death"
      concept. Yersinia pestis presents, besides its bipolar staining, many other
      characteristics such as the indispensable presence of iron to produce virulence,
      or the fermentation of glycerine and reduction of nitrates as parameters for the
      identification of 3 biovars, corresponding with a specific geographic
      distribution: antiqua, medievalis, orientalis or maritima. The antigenic
      structure has been discussed and also the role of plasmids. Plague is a disease
      of rats, a variegated gathering of rodents with different degrees of tolerance
      and sensitiveness to Y.pestis, living in a frail equilibrium. The multimammate
      houserat was in the Ituri the principal agent until the black rat Rattus rattus
      invaded the region and a new balance came into being. The frequent changes in
      taxonomy of Mastomys caused uncertainties. The transmission is due to fleas
      subject to a blocking of their ventriculum by Y.pestis. Fleas play an active part
      in the process. Man is only a casual intruder. The pathogenicity is related to
      its invasiveness and its intracellular localization in macrophages and other R.E.
      cells, in which Y.pestis can survive. The bubo is characteristic of the disease.
      In Zaire a septicaemic tendency has been observed, with a possible involvement of
      the C.N.S. and of the lungs. The latter may produce among the surrounding
      relatives primary pneumonic plague. The clinical diagnosis ought to be confirmed
      by bacteriologic investigation of the puncture fluid of the bubo, the blood, and
      when necessary the C.S.F. or the sputum by culture and/or animal inoculation. The
      treatment became very efficient since the availability of sulfamides and later
      antibiotics: aminoglycosides, chloramphenicol, tetracyclines. A timely
      administration ensures practically recovery. As soon as Y.pestis was identified
      vaccination was put into practice and in the first place by killed germs
      (Haffkine's lymph) to day with formalized F1, for mass vaccination live
      attenuated strains were used: Tjiwidej (Otten), E.V. (Girard), K120
      (Grasset).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7801704
TI  - One aspect of surgical quality assurance: complications in gynaecologic and
      mammary surgery.
AB  - This overview of the operative and post-operative complications encountered in a
      personal series of 10.190 classical surgical procedures out of 43.395 patients
      gives an idea about the nature and rate of problems in the classical way of
      surgery. While there is a new trend to abandon this way of surgery as much as
      possible, it will be useful, when other surgeons publish the results and also the
      complication rate in detail of their new techniques to compare the advantages and
      disadvantages and the final results of the different kinds of surgery. In cases
      of breast cancer the survival after 5, 10 and 15 years, will finally decide about
      all the different ways of treatment used at this moment. A larger and better
      consensus about all these treatments is necessary before a clearer opinion will
      be obtained.

PMID- 7801705
TI  - [Structure, organization and capacity problems in emergency medical services,
      emergency admission and intensive care units].
AB  - Emergency medicine is subjected worldwide to financial stringencies and
      organizational evaluations of cost-effectiveness. The various links in the chain
      of survival are affected differently. Bystander assistance or bystander CPR is
      available in only 30% of the emergencies, response intervals--if at all required
      by legislation--are observed to only a limited degree or are too extended for
      survival in cardiac arrest. A single emergency telephone number is lacking. Too
      many different phone numbers for emergency reporting result in confusion and
      delays. Organizational realities are not fully overcome and impair efficiency.
      The position of the emergency physician in the EMS System is inadequately
      defined, the qualification of too many emergency physicians are unsatisfactory.
      In spite of this, emergency physicians are frequently forced to answer out-of
      hospital emergency calls. Conflicts between emergency physicians and EMTs may be
      overcome by providing both groups with comparable qualifications as well as by
      providing an explicit definition of emergency competence. A further source of
      conflict occurs at the juncture of prehospital and inhospital emergency care in
      the emergency department. Deficiencies on either side play a decisive role. At
      least in principle there are solutions to the deficiencies in the EMSS and in
      intensive care medicine. They are among others: Adequate financial compensation
      of emergency personnel, availability of sufficient numbers of highly qualified
      personnel, availability of a central receiving area with an adjacent emergency
      ward, constant information flow to the dispatch center on the number of available
      emergency beds, maintaining 5% of all beds as emergency beds, establishing
      intermediate care facilities. Efficiency of emergency physician activities can be
      demonstrated in polytraumatized patients or in patients with ventricular
      fibrillation or acute myocardial infarction, in patients with acute myocardial
      insufficiency and other emergency clinical pictures. Cost effectiveness is
      clearly in favor of emergency medicine. Future developments will be characterized
      by the consequences of new health care legislation and by effects of financial
      stringencies on the emergency medical services.

PMID- 7801706
TI  - [Blood coagulation parameters as prognostic factors in multiple trauma: can
      clinical values be an early diagnostic aid?].
AB  - INTRODUCTION: Polytraumatized patients develop complex changes in blood
      coagulation and fibrinolysis even before their arrival at the emergency room
      (ER). Hemostaseological parameters (i.e. antithrombine 3, alpha-2-antiplasmine, D
      dimers) obtained upon admission however, permit advance differentiation of later
      mortality vs. survival and of possible future secondary organ failure with
      varying specification. OBJECTIVES: Which clinical findings enable to identify
      such patients early in the ER even when no specialized hemostaseological
      laboratory is available? MATERIAL AND METHODS: a) Prospective study of 40
      polytraumatized adults upon arrival at the hospital; b) Blood sampling at the
      earliest possible time during takeover in the ER; c) Injury Severity Score (ISS)
      for descriptive purposes; d) Evaluation of the prehospital emergency physician's
      records in regard to respiratory therapy, fluid resuscitation, and arterial blood
      pressure; e) Statistics; Wilcoxon test, Spearman correlation coefficient.
      RESULTS: All 40 patients (m:f = 28:12; mean age: 36 (SD: 16.6) years; mean ISS:
      34.7 (SD: 11.4)) displayed advanced disseminated intravascular coagulation with
      secondary hyperfibrinolysis upon arrival in the ER. The amount of deviation from
      the hemostaseological norm could not be derived from either the correlation of
      the typical activated parameters of coagulation of fibrinolysis with the ISS or
      the analysis of the separate injuries. On the other hand the subgroup of patients
      displaying a systolic blood pressure of less than 100 mmHg at the site of the
      accident or upon arrival at the ER all had significantly lower antithrombine 3,
      protein C, and alpha-2-antiplasmine activities as well as increased
      concentrations of specific reaction products resulting from activated coagulation
      (thrombine-antithrombine 3-complex) and of fibrinolysis (D-dimers). CONCLUSION:
      In our study patients with multiple injuries displaying a systolic blood pressure
      of less than 100 mmHg either at the scene of the accident or upon arrival in the
      ER showed coagulation values which by other investigators were regarded as a sign
      of potential secondary organ failure or death.

PMID- 7801707
TI  - [Primary diagnosis and follow-up after thoracic trauma and lung contusion].
AB  - In 212 patients after injury of the thorax (54 males, 158 females; penetrating
      (15), blunt (197), multiple trauma (128)) 158 cases demonstrated rib fractures
      and 103 radiological proven pneumo- or hematothoraces or sometimes both, 108 of
      138 had to be drained. 96.5% of the effusions and 98% of the pneumothoraces were
      clinical confirmed. 93.5% of 97 pulmonary contusions (79 unilateral, 18
      bilateral) were detected by bronchoscopy within 10 h, 72% by x-ray. Caused by
      anatomical problems or for additional diagnosis 4 patients underwent thoracic CT.
      During ICU treatment 31 patients developed septic complications without detection
      in x-ray studies. In CT (n = 64) we found: 5 empyema, 13 pleural effusions, 4
      pneumothoraces, 4 pneumocysts, 72 condensations of a lobe. After CT we performed:
      9 resections of the lower lobe, 1 pneumectomy, 1 decortication, 7 thoracotomies
      with drainage, 8 drainages. To detect a septic focus under treatment the CT
      proved being an important diagnostic tool in chest trauma and lung contusion.

PMID- 7801708
TI  - [Analysis of 55 post-traumatic pseudarthroses after tibial fracture].
AB  - In a retrospective analysis of 1,300 lower leg fractures, treated by operative
      stabilization in the years from 1980 to 1992, we examined disturbances of bone
      healing. In 55 patients (4.2%) faults in indication and completion of internal or
      external stabilization, infections with consecutive instability (43.6%), and bone
      defects (63.6%) led to prevention of bone healing. Conservation of blood supply
      and medial cortical support should be ensured.

PMID- 7801709
TI  - [Treatment concepts and results in non-infected post-traumatic pseudarthroses of
      the femur and tibia].
AB  - AIM OF INVESTIGATION: Different methods of internal and external fixation are
      used to treat aseptic posttraumatic nonunion of the femur and tibia. The
      advantages and disadvantages of the different methods will be demonstrated by
      analysing the clinical course and the outcome of our patients. Utilizing these
      data, a therapeutic concept tailored to the individual situation is recommended.
      METHODS: Depending on the form of reaction we distinguish between vital and non
      vital nonunions. The classification is made according to the clinical course, x
      ray-findings and in special cases the results of scintigraphy. Due to anatomic
      differences in vascularisation and soft tissue coverage nonunion of the femur and
      the tibia are discussed separately. Stabilisation is achieved by intramedullary
      nail, plate or external fixator. As new methods the internal plate fixator was
      used for the femur and the Ilizarov ring fixator for the tibia. If there has been
      a mistake in the choice of the method of the primary stabilisation a change of
      method is done. If the indication for the initial method of stabilisation was
      correct, the therapy of nonunions is limited to the correction of technical
      mistakes. Additionally, a biologic stimulation is required for the therapy of non
      vital nonunion. RESULTS: The clinical data of 77 patients treated from 1985-1993
      were analysed retrospectively. Vital nonunions of the femur (11) healed after 9.5
      months on the average, those of the tibia (49) after 10 months. The duration of
      treatment of non-vital nonunions was much longer and required 20 and 16 months,
      respectively. The treatment of two non-vital nonunions of the tibia could not be
      completed. For the femur only intramedullary nail (4) and plate (8) were used,
      for the tibia mainly the fixator (43), of these in 18 cases the Ilizarov
      apparatus. Differences in the duration of treatment due to the choice of implant
      could not be recognized. Complications were pin problems (14) and one lesion of
      the peroneal nerve in the fixator group and superficial wound infection (2),
      nerve irritation (1) and fracture (1) in the group treated with intramedullary
      nailing. CONCLUSIONS: Due to the good soft tissue coverage and vascularisation
      internal fixation is favored for the treatment of femoral nonunions. The fixator
      should only be used if distraction osteogenesis is necessary because of a bony
      defect. Due to the problematic soft tissue situation and poorer vascularisation
      on the external fixator is preferred in the treatment of tibial nonunions if a
      change of method is indicated. For this purpose, we currently use predominantly
      the Ilizarov-apparatus because of its biomechanical properties and the convincing
      results. Initial problems with its use could markedly be reduced with growing
      experience.

PMID- 7801710
TI  - [Change in the treatment method of infected pseudarthrosis with bone loss of the
      tibia].
AB  - AIM OF INVESTIGATION: The treatment of nonunions complicated by infection and
      bone loss is divided into two stages. Having calmed down the infection by
      stabilizing, removal of infected and necrotic tissue and local antibacterial
      measures, the bone loss has to be filled up. Bridging the gap by means of
      autogenous cancellous bone grafting is complicated by a high rate of refractures
      depending on the length of bone loss. Therefore after changing the method and
      using the Ilizarov procedure it is of interest, whether this method offers
      advantages. Our experience is to be reported and discussed. METHODS: According to
      the clinical course two groups of patients with nonunions of the tibia
      complicated by infection and bone loss were compared. 25 previously evaluated
      patients of the years 1980/81 whose tibial bone loss was bridged by cancellous
      bone grafting (1st group) were compared with 16 patients who were treated by the
      Ilizarov method from May 1990 to October 1993 (2nd group). The average age was
      nearly the same (32.6/32.9 years). In the first group the average of bone loss
      measured 4 cm, in the second 7.8 cm. The number of initial operations to
      eliminate infection and the duration of fixator application from the beginning of
      bridging bone loss were compared as well as early and late complications,
      especially the rate of refracture and reinfection. RESULTS: 1.2 operations were
      needed to eliminate infection in the first group, in the second only one was
      necessary. The handling of the Ilizarov device is more difficult and needs
      training. The higher rate of early complications at the beginning decreased with
      increasing experience. The average of fixation time could be reduced by about ten
      days per cm of bone loss using the Ilizarov technique. By segmental transport new
      cortical bone is generated which surpasses cancellous bone grafting in regard to
      stability. This seems to be an important reason that refracture did not occur in
      the second group. Furthermore, reinfection could be avoided up to now obviously
      due to sufficient segmental resection of infected and necrotic tissue. Limited
      stores of autogenous cancellous bone are not to be feared. The total number of
      operations can be reduced. At the docking side early single cancellous bone
      grafting is recommended.

PMID- 7801711
TI  - [Treatment of perianal burns with submerged skin particles].
AB  - Perianal burn wounds often cannot be cured by conventional split-thickness skin
      grafting procedures. This is due to the mechanical stress and the enormous
      bacterial colonization. Transplantation of small skin pieces, submerged into the
      granulation tissue, is able to produce small epithelial islands within 2 weeks.
      These enlarge continuously and produce complete epithelialisation in the further
      course. Own results with 7 burn patients prove that this technique is suitable to
      epithelialize gluteal and perianal problem wounds with comparatively little
      expenditure.

PMID- 7801712
TI  - [Isolated talus metastasis of an occult bronchial carcinoma--a rare cause for
      chronic foot disorders].
AB  - A case of a solitary metastatic lesion of the talus from an occult histologically
      confirmed bronchogenic carcinoma is reported. Clinical, radiologic, histological,
      and laboratory manifestations are described. Four months after complete resection
      of the talus and consecutive internal and external fixation of the ankle joint a
      below-knee amputation was done because of progressive infiltration. A review is
      given on reports in the literature of rare cases of solitary metastatic deposits
      of malignant tumors below knee and elbow. This unusual cause of foot pain should
      be taken into account concerning differential diagnosis in elderly patients. A
      mistake for a septic osteolysis is possible.

PMID- 7801713
TI  - [Transthoracic cholecystectomy and choledochus revision in chronic rupture of the
      right diaphragm].
AB  - Case report on a transthoracic cholecystectomy and choledochotomy in a patient
      with a 17 years old rupture of the right diaphragm with liver prolapse into the
      right thorax. Surgical treatment of diseases of the upper abdominal cavity
      combined with a late diagnosed rupture of the diaphragm should be performed
      simultaneously by a transthoracic approach.

PMID- 7801714
TI  - [Myiasis of the scalp--an incidental finding in ambulatory surgery].
AB  - Because of the increase of travels to tropical countries the physician in Germany
      is more often confronted with parasitic tropical diseases. In an apparently
      routine case a 28 year old patient suffered from infected stitches of the scalp,
      caused by an unknown insect, after returning from Sri Lanka. Four larvae of
      Dermatobia hominis, which causes the cutaneous myiasis, were found into the
      pyogenic furuncles and were removed by surgical approach.

PMID- 7801715
TI  - [Formation of a neofascia after implantation of a composite patch in the inguinal
      region].
AB  - In this study, a novel patch material composed of polyglactin 910 and
      polydioxanon was tested in animal experiments for its use in the surgical repair
      of hernias. The material was implanted laparoscopically into the inner inguinal
      region of three hybrid running-pigs. No postoperative complications were
      observed. The animals were killed 14 and 48 days after surgery. Both the
      macroscopic and microscopic examination showed a de novo formation of connective
      tissue at the site of implantation, which may be regarded as a new fascia. Due to
      the cooperation of fibroblasts and free cells of the connective tissue, new
      intercellular matrix was formed after the resorption of the implanted material. A
      model of this cell cooperation is outlined in the study. The technical advantages
      of the implantation material are demonstrated and its benefits for minimally
      invasive surgery emphasized. Because of its special properties, the material may
      be recommended for later clinical traits in the surgery of fascia.

PMID- 7801716
TI  - [The history of surgical instruments: 1. The Mikulicz peritoneal clamp].
AB  - The peritoneal clamp, which has been developed by the Breslau surgeon Johann von
      Mikulicz-Radecki (1850-1905), is presented on the basis of original publications
      from 1900. At this time, Mikulicz had been a full professor of surgery at the
      Medical Faculty of the University of Breslau. After laparotomy, Mikulicz
      recommended to seize the peritoneum with 4 to 8 clamps, developed by him to
      protect the wound of the abdominal wall from manipulations and to prevent a
      retraction of the peritoneum: "The fastened clamps are changed in their position
      in a way, that the grips lie out of the area of the wound on the abdominal wall."
      Moreover, a brief description of the Breslau surgeon's life and work is given.
      Further, we refer on his importance on the development of modern surgery in
      Germany.

PMID- 7801717
TI  - Antigenic analysis of rabies-virus isolates from Latin America and the Caribbean.
AB  - A total of 288 rabies-virus samples from 17 Latin American and Caribbean
      countries were reacted with an array of monoclonal antibodies. Identification of
      eight distinct antigenic variants among these samples permitted epidemiologic
      studies of the geographic distribution of different concentrations of rabies in
      the region and of the animal species serving as maintenance sources for rabies
      within a concentrated area. Two variants were broadly distributed and associated
      with enzootic disease in dogs and vampire bats. All isolates from cases of human
      rabies contained one of these two variants. Two variants had a limited
      distribution: an outbreak in Brazil, primarily affecting dogs and believed to be
      maintained by dog-to-dog transmission, and nine cases of rabies in cattle in
      Venezuela, animal reservoir unknown. A reservoir of rabies in insectivorous bats
      was identified and the associated variant was found in a rabid domestic cat. The
      remaining three rabies variants were found in single isolates only, but due to
      inference from antigenic-typing data from North American samples, were believed
      to be maintained by reservoirs of rabies in hoary bats, foxes, and skunks.

PMID- 7801718
TI  - Biochemical and serological characteristics of Rhodococcus equi isolates from
      animals and humans.
AB  - In the present study, 17 Rhodococcus equi isolates from animals and 13 R. equi
      isolates from humans were correctly identified by the use of the API Coryne-test
      system. The biochemical characteristics revealed no significant differences
      between isolates from animals and humans. Heat extractions at acid pH or
      autoclave extractions of the bacteria and the use of monospecific antisera
      against type antigens 1-7 allowed the serotyping of the bacteria. The majority of
      the R. equi isolates reacted with serotype 1 and serotype 2-specific antisera,
      extracts of two human isolates reacted with serotype 5 and serotype 6-specific
      antisera, respectively. The determination of biochemical and serological
      properties of R. equi might help to characterize individual cultures of this
      species. This might be useful in epidemiological studies.

PMID- 7801719
TI  - Isolation of serovar-specific leptospiral antigens for use in an enzyme-linked
      immunosorbent assay (ELISA) compared with the microscopic agglutination test and
      immunofluorescence.
AB  - A total of 10 different detergents were used with the intention of extracting
      serovar-specific antigens from eight leptospiral serovars for use in an ELISA.
      Extractions with 2% sodium taurocholate at 50 degrees C proved to be best suited
      for this purpose. Taurocholate extracted antigens could be separated in SDS-PAGE
      and antigenic activities demonstrated in immunoblotting. In comparative studies
      on sera taken from cattle, pigs, horses and dogs, the self-made ELISA proved to
      be more sensitive than the microscopic agglutination test (MAT) and the
      immunofluorescence test (IFT). The IFT gave different results from those obtained
      using MAT or ELISA.

PMID- 7801720
TI  - Hygienic aspects of the production and agricultural use of animal wastes.
AB  - Regarding the hygienic aspects of the production and use of animal wastes,
      further research on the following aspects is essential: pathogenic agents present
      in residues of animal production in the context of transmissible multifactorial
      diseases and the epidemiology of pathogens under different ecological conditions;
      recycling of toxic agents, e.g., copper, selenium and iodine, in animal wastes in
      the context of the food chain from soil to humans; hygienic effects of animal
      wastes on water as regards the standards required by medical authorities; effects
      of agents used to increase animal production, or used for medicinal purposes,
      which are present as residues in animal excreta and may be hazardous to public
      health; effects of animal excreta on microbiological processes in the soil;
      effects of dust and airborne microbial emissions from animal production, and
      finally, processes of self-disinfection of manure and livestock slurry during
      storage as a means of reducing the amounts of chemical disinfectants used, of
      reducing environmental pollution, and of studying the application of
      biotechnological methods to disinfect manure and livestock slurry, this study
      being of particular importance.

PMID- 7801721
TI  - [DMSO induced differentiation of human gastric adenocarcinoma cell line MGC 80
      3].
AB  - The in vitro effects of dimethyl sulfoxide (DMSO) on MGC 80-3 cells were studied
      by light microscopy, transmission electron microscopy and biochemical methods.
      The results indicated that the inhibitory effects of DMSO on the growth of MGC 80
      3 cells was concentration dependent and 1.5% DMSO was suitable in the present
      study. The growth rate, mitotic index, colony forming efficiency and Con A
      aggregation of the cells treated with 1.5% DMSO in vitro for 7 days was reduced
      respectively by 35.15%, 18/1000, 90% and 55.8%. It was remarkable that the
      activity of membrane-associated alkaline phosphatase, which is not presented in
      normal human gastric mucosa, was decreased by 90% in the treated cells. There was
      a 75% decrease of the rate of tumorigenesis in the treated cells as compared with
      the tumorigenic rate of the untreated MGC 80-3 cells inoculated into nude mice.
      Gross morphological changes of MGC 80-3 cells treated with 1.5% DMSO were evident
      including enlargement and flatness of the cells, stumpy microvillies instead of
      long and rigid ones, and extremely well-developed Golgi apparatus and rough
      endoplasmic reticulum. This data indicated that DMSO was able to induce
      differentiation of MGC 80-3 cells and change their malignant phenotypes.

PMID- 7801722
TI  - [Intracellular free calcium changes of mouse oocytes during activation induced by
      ethanol or electrical stimulations and parthenogenetic development].
AB  - Oocytes collected 18-19 h after HCG injection were stimulated with 7-8% ethanol
      or electrical pulses (1.7 KV/cm field strength, 80-100 microseconds duration, 3-4
      times, 5-6 min interval). The parthenogenetic embryos derived from the above
      mentioned methods developed to blastocyst stage just like those developed from
      fertilized eggs. Mouse oocytes were rather sensitive to ethanol stimulation. More
      than 95% of the treated oocytes were activated after stimulation of 7-8% ethanol
      for 5 min. Multiple electrical stimulations induced higher activation percentages
      of oocytes than only single electrical stimulation (71.5% vs. 63.6%). Intact
      oocytes were loaded with fluorescent Ca2+ indicator fura-2 and intracellular free
      calcium changes during artificial activation were measured by fluorescence
      detector. The results showed that ethanol could induce repetitive transient Ca2+
      concentration increase in activated oocytes. Single electrical stimulation only
      induced single free calcium concentration elevation in oocyte while multiple
      electrical pulses could induce repetitive Ca2+ increase (each electrical pulse
      elicited the corresponding Ca2+ concentration peak). The pronuclei were not
      observed in the oocytes which had not exhibited calcium concentration rise during
      activation. Apart from electrical stimulation parameter, sufficient amount of
      Ca2+ in electric medium was crucial to mouse oocyte activation when stimulated
      with electrical pulses. The oocytes were hardly activated by electrical
      stimulations in a medium without Ca2+ even with longer pulse duration and the
      intracellular free calcium concentration in the oocytes showed no elevation. This
      indicates that the inflow of extracellular Ca2+ from tiny pores across the oocyte
      membrane caused by electrical stimulation is the main source of intracellular
      free calcium increase.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7801723
TI  - [Effect of concanavalin A on morphology and DNA synthesis of resting chondrocyte
      cultures].
AB  - Rabbit chondrocytes were isolated from resting cartilage of ribs of 4-week-old
      New Zealand rabbits. Chondrocytes were seeded at low density and grown to
      confluency in medium (DME) with 10% fetal bovine serum, 50 micrograms/ml ascorbic
      acid, and antibiotics, at 37 degrees C under 5% CO2 in air, and then serum
      concentration was reduced to 0.3%. At the low serum concentration, chondrocytes
      adopted fibroblastic morphology. Addition of concanavalin A to the culture medium
      induced a morphologic alteration of the fibroblastic cells to polygonal or
      spherical chondrocytes that were surrounded by refractile matrix. Wheat germ
      agglutinin and garden pea lectin induced similar cell shape changes without any
      increase in matrix synthesis. Concanavalin A decreased [3H]thymidine
      incorporation into DNA in a dose-dependent manner with an ED50 of 0.4-1
      micrograms/ml in the presence of various concentrations of serum ranging from 0.3
      to 20%. The concanavalin A inhibition of DNA synthesis was abolished by 10 mmol/L
      methyl-D-mannopyranoside. The inhibition of chondrocyte proliferation does not
      seem to be specific to concanavalin A. Wheat germ agglutinin, lentil lectin,
      phytohemagglutinin, Ulex europeaus agglutinin, and garden pea lectin also
      decreased, dose-dependently, [3H]thymidine incorporation into DNA in
      chondrocytes. Other lectins at 0.01-20 micrograms/ml had little effect on [3H]
      thymidine incorporation. Because the molecular structure of concanavalin A and
      its mode of actions have been extensively characterized, chondrocytes exposed to
      this lectin will be useful as a novel model in studying of the control of
      cellular differentiation.

PMID- 7801724
TI  - [The role of TNF-alpha in the growth and differentiation of U937 cells induced by
      PMA and IFN-gamma].
AB  - The effects of PMA and IFN-gamma on regulation of growth and differentiation of
      human monoblastic leukemic cell U937 were examined. U937 cells were stimulated by
      different concentrations of PMA and IFN-gamma respectively and NBT reduction
      assay was used to detect the differentiation of the cells. The results showed
      that both PMA and IFN-gamma dose-dependently induced differentiation of U937
      cells into mature macrophage-like cells. The data also revealed a time-course
      response in the differentiation induction. Moreover, the U937 cell growth was
      significantly inhibited by the treatment of PMA and IFN-gamma. These results
      suggest that PMA and IFN-gamma coupled the regulation of U937 cell growth and
      differentiation. It was found that tumor necrosis factor-alpha (TNF-alpha) was
      expressed by the stimulated U937 cells. The specific monoclonal antibody against
      TNF-alpha diminished the effects of PMA and IFN-gamma on the growth and
      differentiation of U937 cells. Thus the endogenous TNF-alpha may involved in the
      mechanism of the effects of PMA and IFN-gamma on the differentiation of U937
      cells. The regulatory action of the endogenous TNF-alpha on U937 cells was not
      due to its cytotoxic effect.

PMID- 7801725
TI  - [The study of the relationships between the processes of denucleation and
      vimentin, lamin].
AB  - By employing K-RRneo cells which were cybridized between rabbit reticulocytes and
      the K562 cells, the relationships between the denucleation and vimentin/lamin
      were studied. It was demonstrated that, accompanying with the differentiation and
      denucleation of K-RRneo cells, the expression of vimentin mRNA and lamin proteins
      were significantly reduced. These results testified our earlier conclusion drawn
      from the whole mount and Western blot studies, and would provide a basis for
      further elucidation of the mechanism of erythroblast denucleation.

PMID- 7801726
TI  - [Construction and application of the chromosomal specific probe pool from human
      chromosome no. 7].
AB  - We constructed a chromosomal specific probe pool from human chromosome No. 7
      using the techniques of chromosomal microdissection, PCR and chromosomal
      painting. A patient's pedigree with an abnormal chromosome No. 7 were analysed by
      the above probe pool.

PMID- 7801727
TI  - [Studies on a new tumor marker with monoclonal antibody against human colorectal
      carcinoma antigen].
AB  - A hybridoma 1 G 10 clone was derived from fusion between SP 2/0- Ag14 myeloma
      cells and spleen cells of BALB/C mice immunized with the soluble Noridet P40
      extracts from a human colonic adenocarcinoma cell line SW 620. The 1 G 10 clone
      was identified to be able to produce monoclonal antibody of IgG1 subclass which
      had sufficient titer for immunoreactivity to both extracts from SW 620 cells and
      surgical colonic carcinoma tissues, but no immunoreactivity to both extracts from
      normal adult colorectal tissues, mixed human lymphocytes and normal human serum
      (NHS) as well as carcinoma embryonic antigen (CEA) by enzyme-linked immunosorbent
      assay (ELISA). By affinity column on Sepharose 4 B coupled with 1 G 10 IgG,
      colonic carcinoma-associated antigen (CCA) was purified from SW 620 cell extracts
      and thoracic ascitic fluid of a patient with lung adenocarcinoma. Western
      blotting analysis with 1 G 10 IgG demonstrated that one immunoreactive bands
      corresponding to 55 Kd molecule was observed in the samples of ascitic fluid and
      SW 620 cell extracts. The 55 Kd band could be stained with Alcian blue. The
      immunoreactivity of CCA to 1 G 10 antibody could be abolished completely by the
      treatment of the antigen with NaIO4 and proteinase K. These results indicated
      that the determinants of CCA reacted with 1 G 10 monoclonal antibody are probably
      both present in polysaccharide and protein part of the molecule. The specificity
      of anti-CCA 1 G 10 monoclonal antibody and its possible application for clinical
      oncology were discussed.

PMID- 7801728
TI  - Metabolic rate and body size: a new view on the 'surface law' for basic metabolic
      rate.
AB  - In larger animals a considerable part of the total body mass (e.g. body water,
      dissolved substances, mineral and organic deposits) does not consume significant
      amounts of oxygen. These materials can be considered to form a metabolically
      inert infrastructure which mainly serves three functions: (1) structural support
      to the organism, (2) storage of nutrients (building material and energy stores)
      and (3) transport and distribution of these materials. Considering the transport
      and support function of the metabolically inert structures and their
      interconnections it is likely that the infrastructure will basically show some
      tree-like, branching building plan. The weight of the metabolically inert
      infrastructure of an organism, can be given by bW/(c+W), in which W = body
      weight, b and c are constants. With increasing size the weight of the metabolic
      inert infrastructure increases disproportionably. Experimental data concerning
      basic metabolic rate (M) in relation to body weight (W) better fit the equation M
      = a W (1-bW/(c+W), (a = constant) than the conventional power law.

PMID- 7801729
TI  - Ab-Ag affinity thresholds in inventory optimization.
AB  - The role of antibody-antigen affinity and concentrations in adaptive antibody
      response is analyzed in a framework of probabilistic inventory model for antibody
      production. Our results indicate significant differences in optimal behaviours of
      low, moderate and high affinity groups and offer important implications.
      Interestingly, the involved approach is also of relevance in other production
      systems. Directions for its applications in industries and information sciences
      are also presented.

PMID- 7801730
TI  - An energy imbalance (cellular energy lesion) as an etiological factor in the
      development of cancer: a new insight.

PMID- 7801731
TI  - [Calyceal diverticula: notes on endourological technique].
AB  - Percutaneous approach to complicated small caliceal diverticula is the first
      choice therapy. Generally, the open surgery is used large diverticula with renal
      parenchymal damage but, in selected cases, a percutaneous (PCN) treatment may be
      an effective alternative. The Authors report a case of inferior caliceal
      diverticulum associated to a parenchymal damage successfully treated using
      directed PCN management (electrical fulguration) and consequent injection of
      human fibrin glue.

PMID- 7801732
TI  - [Tumors of the thoracic wall. Our experience].
AB  - Chest wall tumors are rare being less than 1% of all the neoplasms. While the
      treatment of benign tumor and of solitary metastatic is standardized, the therapy
      of the primary malignant is not the same for all the authors. From January 1980
      to December 1993 46 patients affected by chest wall neoplasms, 29 men (63%) and
      17 women (37%), mean age of 51 yrs. (range 31-77 yrs.), were treated surgically.
      For benign tumors only resection was performed while for malignant and metastatic
      tumors after the resection the reconstruction was performed respectively: in 11
      cases with Marlex mesh, in 1 case with the omentum, in 2 cases with Marlex and
      Methyl Methacrylate. Muscle transposition was performed in 1 case with pectoralis
      major covering a Dura Mater prosthesis. We have no peroperative death and no
      complications in 37 (80%) patients. Minor complications in 9 cases; in 1 case the
      sternal prosthesis was removed for infection. The median follow up was of 40.50
      months. Actually the 48% of patients with primary and metastatic tumor are alive.
      From our results we conclude that the wide radical resection with reconstruction
      when necessary is the treatment of choice for the tumors of the chest wall.

PMID- 7801733
TI  - Verapamil used in lung transplantation: could it have a cytoprotective effect
      during the ischemic phase of pulmonary preservation? Study on alveolar type II
      cells.
AB  - It has been shown that Verapamil (V) improves lung preservation, but it is not
      clear whether the effect is due to vasodilation, with a more homogeneous cooling
      effect during hypothermic preservation, or a direct cytoprotection. Attempting to
      verify this, we studied the cellular viability of rats' pneumocytes type II
      primary cultures separately incubated in the first experiment for 6 hours in
      Ringer Lactate (RL) +/- V (10 mg/l) at 25 degrees C and at 4 degrees C, and in
      the second experiment for the same period in RL, EuroCollins (EC) and Collins
      (CL) solution +/- V (10 mg/l) at 4 degrees C. We analyzed the influence of the
      drug using two methods: the total protein content in each culture and the
      metabolic function of the cells using the rate of protein synthesis by means of
      35 S methionine uptake assay. All data showed that there were no significant
      statistical difference (Student t-test, p > 0.05) in the use of verapamil during
      alveolar type II cells either in normothermic or hypothermic preservation. Thus
      we conclude that the protection of this calcium channel blocker during lung
      preservation is probably due to the effect on pulmonary vessels rather than to a
      direct cytoprotective effect on the lung cells.

PMID- 7801734
TI  - [Stereotactic fine-needle aspiration biopsy (FNAB) of nonpalpable breast lesions:
      cyto-histological correlations].
AB  - There are not complete consensus if mammographically guided FNABs of nonpalpable
      breast lesions can replace open biopsy. To elucidate this problem, we have
      reviewed the efficacy of stereotactic FNAB in a series of 502 cases of
      nonpalpable lesions observed in a period from 1990 to 1994, with a immediate
      cytologic control of adequacy of material. In 144 patients of the lesion is
      achieved with 4% sterile coal localisation and an open biopsy of the area
      performed. In each case cytologic findings, with a brief description of probable
      histotype of the lesion, are correlate with surgical pathologic diagnosis, with a
      comparison between two time period (1990-92; 1993-94). In our study particularly
      ductal and lobular hyperplasia (with or without atypia) restrict the efficiency
      of the FNAB. In fact the specificity varies from 83.3% to 90.3%, the sensitivity
      from 78.7% to 77.8%, positive predictive value from 86.0% to 90.3%, negative
      predictive value from 75.6% to 70% and diagnostic accuracy from 80.0 to 82.4%,
      considering ductal and lobular hyperplasias as true negatives or true suspects.
      Cytologically we have 2 false positive in the first period of time, 3 false
      suspects in the second period of time and 7 false negatives. However
      benign/malign biopsy ratio is well (0.97). Moreover histopathologic informations
      of cytological diagnosis is variable according the histotype of the lesion. In
      conclusion our study confirm that FNAB is an reliable method that avoid
      unnecessary biopsy but is insufficiently sensitive to replace open biopsy of
      nonpalpable breast lesions, also with an immediate cytological control of
      adequacy of aspirate.

PMID- 7801735
TI  - Follow-up study of MS patients treated with high-dose intravenous
      methylprednisolone.
AB  - In a longitudinal prospective study, we followed 56 patients (17 men, 29 women)
      with definite multiple sclerosis (MS), who were treated with high-dose
      intravenous methylprednisolone (IVMP), 10 consecutive days with 1000 mg IVMP
      daily. Mean follow-up period after entry was 2.6 years (range 1.7-3.5 yrs). All
      patients were treated because of a symptomatic deterioration. Independent of the
      disease courses (RR-relapsing remitting/CP-chronic progressive/CP+RR- mixed
      course), 65% of the 46 MS patients (30/46) showed a clinical improvement after
      the first IVMP course, expressed by a decrease in the EDSS rating (1.0 point or
      more). During the follow-up period 59 additional IVMP courses (range 0-5 courses
      per patient) were given; 8 patients were treated with a combination of
      cyclophosphamide and prednisone, because of strong continuous progression. During
      the follow-up period 19 patients (41%) showed an increase in the EDSS-rating (1.0
      point or more) compared with the EDSS level just after the first IVMP; 22
      patients (48%) had no changes in the EDSS-rating, and 5 patients (11%) showed a
      clinical improvement (decrease of 1.0 point or more). In the relapsing MS
      patients (RR and CP+RR, n = 38) mean relapse rate/patient/year prior to the first
      IVMP was 2.6, which significantly (p < 0.0001) decreased to 0.8 during the follow
      up period. Statistically no significant difference was found between baseline
      EDSS and EDSS ratings after the follow-up period in relapsing MS
      patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7801736
TI  - Prevalence of Parkinson's disease in the elderly: a population study in Gironde,
      France.
AB  - We investigated the prevalence of Parkinson's disease in a representative sample
      of the elderly population living in the Gironde departement, France. Among 3149
      people over age 65, the prevalence ratio for Parkinson's disease was 1.4%,
      without significant difference between men and women. We found that age-specific
      prevalence ratios increased with age from 0.5% in the age group 65 to 69 to 6.1%
      in individuals over age 90. This age pattern is consistent with that found in
      other population-based studies. Interestingly, the slope of age-specific
      prevalence ratios for Parkinson's disease was similar to that previously reported
      for Lewy bodies. Our study showed that a high proportion (42%) of Parkinson's
      disease cases in elderly subjects living in institutions were undiagnosed.

PMID- 7801737
TI  - Altered attentional processing of background stimuli in Gilles de la Tourette
      syndrome: a study in auditory event-related potentials evoked in an oddball
      paradigm.
AB  - In 24 adults and 29 children both with Gilles de la Tourette syndrome and in 24
      control adults and 17 control children we studied auditory event-related
      potentials (ERP's) evoked in 2 different oddball paradigms: a passive listening
      paradigm (PLP) in which subjects had only to attend tones (260 standards, 40
      deviants), followed by an active discrimination paradigm (ADP) in which subjects
      had to press a microswitch in response to the deviant tones. In the adult
      Tourette patients the PLP disclosed between 200-300 msec at all derivations (Fz,
      Cz, Pz, C3, C4, P3, P4) a significantly more negative activity than in the
      controls. In the Tourette children such a result was only found at Fz. In the ADP
      the differences between both adult groups disappeared, but the curves of the
      control children became now significantly more positive than those of the
      Tourette ones except at C3 and P3. Between 200-300 msec the curves of all 4
      groups were significantly less negative in the ADP than in the PLP. This decrease
      in negativity was significantly larger in the adult Tourette patients than in the
      adult controls, but in the children groups the reverse occurred. It is
      hypothesized that the differences in amplitude between patients and controls and
      between both paradigms are due to differences in amplitude of an endogenous
      negative component overlapping the exogenous N100-N200 standard curve. Based on
      this hypothesis the results could suggest that one of the problems in Tourette
      syndrome is an increased attention to non-relevant stimuli.

PMID- 7801738
TI  - Neurovascular complications of cocaine.
AB  - Use of cocaine in the USA, has reached epidemic proportions since 1983, when
      "crack" was introduced, its higher potency compared with cocaine HCl has been
      associated with a tremendous increase in the incidence of strokes. This study
      reports our experience with 55 cases of neurovascular events (25 ischemic and 30
      hemorrhagic) related to cocaine use in 54 patients. Only 15 patients had other
      risk factors for stroke. Twenty six patients smoked "crack", 10 snorted cocaine
      and 12 injected it intravenously. Strokes occurred within 3 h of cocaine use in
      15 patients with infarcts and 17 with hemorrhages. Ten infarcts occurred after an
      overnight binge. Of the hemorrhage group 9 were subarachnoid, 16 intracerebral (8
      basal ganglia, 7 hemispheric and one brain stem) and 5 intraventricular.
      Computerized tomography (CT) showed an aneurysm of the anterior communicating
      artery, as well as one of the vein of Galen. Four aneurysms and 3 AVMs were
      identified on angiography. CT revealed 15 infarcts; it was normal in 7 patients
      with pure motor hemiparesis and in 3 with findings consistent with anterior
      spinal artery infarction. Several mechanisms may be responsible for the
      cerebrovascular complications. A sudden rise in systemic arterial pressure may
      cause hemorrhages, frequently in association with an underlying aneurysm or AVM.
      Vasospasm, arteritis, myocardial infarction with cardiac arrhythmias and
      increased platelet aggregation may provoke infarcts.

PMID- 7801740
TI  - Efficacy of carbamazepine with respect to distribution of carbamazepine and its
      metabolite 10,11-epoxide in cerebral tumours and paratumorous cortex.

PMID- 7801739
TI  - Effects of the antidepressant drug viloxazine on oxcarbazepine and its
      hydroxylated metabolites in patients with epilepsy.
AB  - The effects of Viloxazine (VLX, 100 mg b.i.d. for 10 days) on the steady-state
      plasma concentrations of Oxcarbazepine (OXC), its active metabolite 10, 11
      dihydro-10-hydroxy-carbazepine (MHD) and the corresponding diol (DHD) were
      studied in a randomized, double-blind cross-over placebo-controlled trial in 6
      epileptic patients stabilized on a fixed dosage of OXC. Administration of VLX
      resulted in an 11% increase in the plasma concentration of MHD (p = 0.003)
      associated with a 31% fall in DHD levels (p = 0.0001). Plasma concentrations of
      unchanged OXC were unaffected by VLX. No changes in seizure frequency nor signs
      of drug toxicity were observed during the study. Although VLX may inhibit the
      conversion of MHD to the inactive diol, the interaction is unlikely to be of
      clinical significance.

PMID- 7801741
TI  - Plasma concentrations of prolactin, noradrenaline, vasopressin and oxytocin
      during and after a prolonged epileptic seizure.
AB  - The time course and extent of changes in plasma prolactin, noradrenaline,
      vasopressin and oxytocin levels is reported following serial observations of a
      prolonged epileptic seizure arising in the temporal lobe, recorded by video-EEG
      telemetry, in which the epileptic activity evolved from a simple partial to
      complex partial to secondarily generalised attack. The prolactin levels were
      markedly elevated during the phase of the simple partial seizure, at a time when
      consciousness was preserved, when motor activity was minimal and when EEG
      activity was highly localised. The hormonal levels continued to rise during the
      subsequent seizure evolution, suggesting that the duration (or intensity) of the
      seizure is an important, perhaps the most important, factor determining the
      degree of prolactin release during limbic seizures. Indeed, the prolactin
      elevation in this case (26 times the baseline level) is higher than any
      previously recorded, reflecting the unusual duration and intensity of this
      seizure. We did not observe the phenomenon of "exhaustion" of prolactin release
      and levels peaked after 49 min, and were high for over 2 h after the onset of the
      seizure, and after the convulsion had ceased. The concentrations of vasopressin,
      oxytocin and noradrenaline remained low during the aura, but rapidly increased
      during the phase of generalisation. The oxytocin and noradrenaline levels peaked
      during the phase of generalised convulsion, but the vasopressin levels peaked
      well into the post ictal phase, and remained high for several hours.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7801742
TI  - Prognostic indicators for mortality in transient ischemic attack and minor
      stroke.
AB  - In a prospective study, 129 consecutive patients with transient ischemic attacks
      (TIAs) and 80 consecutive patients with minor ischemic stroke, involving the
      carotid artery territory in both cases, were followed-up for six years from their
      inclusion during the period from January 1984 to October 1985. All patients were
      40-80 years old at inclusion, the median age being 74 years in the TIA group and
      76 years in the minor stroke group. Overall mortality in the TIA group was
      significantly higher than in the minor stroke group, [44%, (57/129) vs 20%
      (16/80), p < 0.0006 after correction for age], and that in the general population
      of Malmo. Pre-existing vascular disease was slightly more prevalent in the TIA
      than in the minor stroke group [27% (35/129 vs 21% (17/80), NS]. Of the 19
      patients with intermittent claudication, who all died [12 (63%) of them due to
      myocardial infarction (MI)], 18 belonged to the TIA group and only one to the
      minor stroke group. The respective frequencies of the putative risk factors in
      the TIA and minor stroke groups were 28% (36/129) vs 9% (7/80) for hypertension
      (p = 0.016), 9% (12/129) vs 6% (5/80) for diabetes mellitus (NS), and 8% (10/129)
      vs 9% (7/80) for cardiac arrhythmia (NS). Mortality due to MI was higher in the
      TIA than in the minor stroke group[24% (31/129) vs 6% (5/80), p = 0.001]. Of the
      minor stroke patients, none without vascular disease died of MI.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7801744
TI  - The anticardiolipin antibody in elderly stroke patients: its effects on stroke
      types, recurrence, and the coagulation-fibrinolysis system.
AB  - Anticardiolipin antibody (aCL) is known as a risk marker for stroke, particularly
      in subjects younger than 50 years of age. We studied the effects of aCL on stroke
      types, recurrences, and the coagulation-fibrinolysis system in 257 elderly
      patients (63.2 +/- 11.4 years). Follow-up was performed for 3.1 years on 184
      patients, for whom the rate of symptomatic and asymptomatic reinfarcts on CT was
      studied. aCL was positive in 30 (12%) of the patients. The incidence of
      atherosclerotic changes in the cerebral arteries was not significantly different
      between aCL-positive and aCL-negative patients. The aCL-positive patients had a
      greater rate of individuals not having any of the known risk factors (p < 0.05),
      a greater incidence of cortical infarctions (p < 0.05), more frequent symptomatic
      recurrences (p < 0.05). They had significantly greater changes in molecular
      markers for the coagulation-fibrinolysis system in the acute phase (p < 0.05),
      but not in the chronic phase.

PMID- 7801743
TI  - Frequency and characteristics of early seizures in Chinese acute stroke.
AB  - We retrospectively studied 1200 hospitalized acute strokes of all etiologies
      between July 1990 and August 1992. Ninety-six % of all strokes underwent computed
      tomography of the head. Fifty-eight percent of the 1200 strokes were brain
      infarction, 32% brain hemorrhage, 6% subarachnoid hemorrhage and 4% were other
      stroke subtypes. Thirty (2.5%) of all strokes suffered from early seizures. The
      incidences of early seizures were 2.8% in brain hemorrhage, 2.3% in brain
      infarction, 2.7% in subarachnoid hemorrhage and 2% in other stroke subtypes.
      Early seizures were documented in 6% of the patients with carotid territory
      cortical infarctions and 12% of the patients with lobar hemorrhage, whereas only
      0.6% of the patients without carotid territory cortical infarctions and 0.6% of
      the patients without lobar hemorrhage were affected. Sixty-six percent of 30
      early seizures were partial seizures, 24% generalized and status epilepticus were
      seen only in 10%. In conclusion, we found the early seizure incidence was 2.5% in
      Chinese patients hospitalized with acute strokes. There was no correlation
      between seizure occurrence and stroke subtypes. Early seizure developed
      significantly higher in acute stroke patients with lesions of the cortex than
      those patients without cortical involvement. The partial seizures were the most
      frequent type occurring in 66% of all acute stroke patients with early seizures.

PMID- 7801745
TI  - Effect of hypothermia and delayed thrombolysis in a rat embolic stroke model.
AB  - Effect of hypothermia on cerebral infarcts was studied in rats embolized in the
      right carotid territory. Thirty-four served as normothermic controls receiving
      saline infusion only. In 16 rats hypothermia of 32 degrees C was induced by
      cooling with a fan, followed by embolization. The rats were kept hypothermic for
      the following 3 h before body temperature was raised to 37 degrees C. In 26 rats,
      treatment with human recombinant tissue plasminogen activator (20 mg/kg i.v.
      during 45 min), started 2 h after embolization. Finally, 14 rats were treated
      similarly with hypothermia for 3 h followed by additional rt-PA treatment
      starting after 2 h. Thrombolytic therapy reduced median infarct volume from 19.5%
      of affected hemisphere among controls to 4.6% (p = 0.006) in the treated group.
      Three hours of hypothermia reduced infarct volume to 1.6% (p = 0.0007).
      Additional rt-PA could not demonstrate further improvement in this experimental
      setting.

PMID- 7801746
TI  - Rhythmic oscillations with a wavelength of 0.5-2 min in transcranial Doppler
      recordings.
AB  - We have studied intracranial pressure (ICP) B-waves and their association with
      rhythmic changes in blood flow velocity (B-wave equivalents) by transcranial
      Doppler sonography (TCD) monitoring. In overnight TCD recordings in 10 normal
      young adults, these rhythmic changes in blood flow velocity were higher and more
      frequent during REM sleep and sleep stage 1 than during other sleep stages. B
      wave equivalents also had a longer wavelength during REM sleep. Their relative
      frequency in these normal subjects over one night ranged from 35 to 73%.
      Peripheral resistance (assessed by the Pourcelot index) was lower and heart rate
      was higher at the peak of these oscillations. These results support the
      hypothesis that ICP B-waves are caused by vasodilation. A non-linear relationship
      between ICP and blood flow velocity was found during B-waves in 9 of 11 patients
      with suspected NPH. Our results throw doubt on the suggestion that a relative
      frequency of less than 80% B-wave activity can be a valid indicator for shunt
      responsiveness in patients with suspected normal pressure hydrocephalus (NPH).
      ICP recordings in suspected NPH should be accompanied by polysomnography to avoid
      misleading results due to variability of B-wave appearance dependent on sleep
      pattern.

PMID- 7801748
TI  - On bias.
AB  - We performed a search in Medline to assess the quality of clinical journals in
      orthopedics from the point of view of study design. 3 levels of quality were
      chosen: prospective studies, random allocation or double-blind methods and
      randomized controlled trials; all entries were Medical Subject Headings (MeSH).
      Out of 25,538 articles indexed in Medline since 1966-1993 in the 8 most cited
      general orthopedic journals, 994 were indexed as prospective studies, while 138
      were indexed as randomized, controlled trials. In recent years the number of well
      designed articles has increased, as has the percentage. In a random check of 208
      articles, approximately half were of a clinical type where these issues can be
      addressed. The agreement between the manual check and Medline indexing was good,
      but not perfect. It was concluded that the retrospective study representing
      clinical production control accounts for the vast majority of all published
      clinical articles in orthopedics. In recent years, a sharp increase in controlled
      trials had, however, occurred.

PMID- 7801747
TI  - Goran Carl Harald Bauer. 1923-1994.

PMID- 7801749
TI  - Revision THR after periprosthetic femoral fractures. An analysis of 23 cases.
AB  - 23 consecutive proximal femoral fractures in 22 patients, who had previously
      undergone total hip arthroplasty, were treated with long revision stems. At the
      time of the fracture, 21 stems were loose. An uncemented Wagner revision stem was
      used in 9 cases and different conventional revision stems in the others. All
      fractures healed, but 7 of the conventional revision implants rapidly loosened
      again, whereas so far none of the Wagner stems have loosened.

PMID- 7801750
TI  - Radiographic determination of the anatomic hip joint center. A cadaver study.
AB  - We studied 31 human pelvic cadaver specimens with 57 intact hip joints. The
      teardrop, which represents the inferior portion of the acetabular notch, was
      identified as also was the center of rotation in the articulating femoral head.
      The pelvic height and the horizontal and vertical distances between the
      acetabular notch and the hip joint center were measured. We found the center of
      rotation of the hip joint to be 13 percent of the pelvic height lateral and 7
      percent of the pelvic height superior to the teardrop. No sex difference was
      found.

PMID- 7801751
TI  - Penetrating cervical hip fracture screws. Report of 4 cases.

PMID- 7801752
TI  - Bony atrophy after mega total hip replacement for bone tumors. 11 cases followed
      for 3-15 years.
AB  - We followed 11 patients 3-15 years after a cemented mega total hip replacement
      for a proximal femoral bone tumor. 7/8 survivors had good function and only
      occasional pain. 1 hip had been revised because of deep infection and in 1 case
      the cup had been exchanged because of aseptic loosening. 2 patients had been
      operated on because of local recurrence of the tumor. At follow-up, 1 patient had
      radiographic signs of loosening of the stem after 7 years. There was in 8 cases a
      pronounced athropy of the femoral cortical bone, not correlated to loosening of
      the stem.

PMID- 7801753
TI  - Cemented versus uncemented socket in hip arthroplasty. A radiostereometric study
      of 60 randomized hips followed for 2 years.
AB  - 60 patients with arthrosis who received a Charnley total hip replacement were
      randomly assigned to either an uncemented porous Harris-Galante type I socket or
      a cemented all-polyethylene Charnley socket. Socket migration and rotation were
      studied by radiostereometry (RSA) for 2 years. After 2 years, all sockets were
      still in situ. There was no difference in migration or rotation between the 2
      socket designs, nor was there any difference in pain or function. We conclude
      that the initial fixation of the Harris-Galante socket resembles that of the
      Charnley socket.

PMID- 7801754
TI  - Vertebral body index and bone mineral density in women with spinal fractures. 66
      probands compared with controls.
AB  - The bone mineral density (BMD) was measured in 61 women with compression
      fractures of the spine and 66 normal pre-menopausal women. Radiographs of the
      lateral spine were also obtained and the vertebral body index (VBI) was measured
      in the region L2-L4. Women with spinal fractures had lower BMD and VBI values.
      Using both BMD and VBI, 3 regions of fracture risk were defined. All but 2 of the
      fracture patients were in the moderate- or high-risk region for fracture.

PMID- 7801755
TI  - MRI and neurology in acute whiplash trauma. No correlation in prospective
      examination of 39 cases.
AB  - 39 consecutive cases of whiplash injury of the neck were examined clinically and
      with MRI at a mean of 11 days after trauma. 26 of these showed changes on MRI
      with disc lesions in 25, 10 of which were classified as disc herniations, and a
      muscle lesion in 1 case. All had neck pain or headache. 29 cases had neurological
      deficits, mostly sensibility disturbances. 22 of the 26 cases with pathologic MRI
      findings had neurological signs, as had 7 of the 10 cases with disc herniation.
      The relationship between the MRI findings and the clinical symptoms and signs was
      poor.

PMID- 7801756
TI  - Intercondylar notch width and the risk for anterior cruciate ligament rupture. A
      case-control study in 46 female handball players.
AB  - We measured the intercondylar notch of the femur in female handball players from
      radiographs of 20 players with previous unilateral anterior cruciate ligament
      injury, and 26 controls without injury. The groups were comparable regarding age,
      height, weight and level of performance. Intercondylar fossa radiographs were
      obtained in a posteroanterior axial position. The anterior opening of the
      intercondylar notch was narrower in the healthy knee of the injured group
      compared to the controls. There was an increased risk of anterior cruciate
      ligament injury associated with decreasing notch opening: female handball players
      with 17 mm or less anterior notch width were 6 times more susceptible to anterior
      cruciate ligament injury compared to players with wider notch width.

PMID- 7801757
TI  - Effect of a cooled saw blade on prosthesis fixation. Randomized radiostereometry
      of 33 knee cases.
AB  - Tibial migration in 33 cementless total knee replacements, which were performed
      with a cooled saw blade vs. a conventional blade, was studied in a randomized
      prospective study using roentgen stereophotogrammetric analysis
      (radiostereometry). All cases were clinically successful after 2 years and
      inducible displacement was smaller in the group operated with the cooled saw
      blade. This group also had a tendency towards less continuous migration.

PMID- 7801758
TI  - Passive muscle tension augments the anterior cruciate ligament. An in vivo study
      in the rat.
AB  - The contribution by passive muscle tension to the structural load-bearing
      capacity of the anterior (cruciate) ligament in the anesthetized rat was
      investigated. Using a stereomicroscope, the joint capsule and ligaments of the
      right knee, except the anterior ligament, were cut and the menisci removed
      leaving the anterior ligament and the tendons of the denervated muscle to
      constrain the knee. The ligament was tested in tension until failure, using a
      loading rate of 2.5 mm s-1 (approximately 0.6 s-1). As a control, the femur
      anterior ligament-tibia complex of the left knee was tested. The mean ultimate
      tensile load on the anterior ligament augmented by muscle tendons was 48 percent
      higher. The energy absorption at failure was 84 percent higher; and the stiffness
      26 percent higher. The deformation remained unchanged. This investigation
      suggests that, when the strain rate is high, muscle may be passively stretched
      and thus absorb energy and increase the force needed to rupture the anterior
      ligament.

PMID- 7801759
TI  - Chevron osteotomy for hallux valgus not improved by additional adductor tenotomy.
      A prospective, randomized study of 84 patients.
AB  - We investigated 106 feet in 84 patients in a prospective randomized series where
      the clinical and radiographic results of the original chevron osteotomy were
      compared to the same procedure with the addition of an adductor tenotomy in
      patients averaging 47 years of age and with a mean follow-up of 3 years.
      Clinically there was no difference in the satisfaction rate of the two groups,
      with 58 satisfied and partially satisfied in the 62 operated by chevron osteotomy
      alone, and 42 of 44 in the group where adductor tenotomy was added. The hallux
      valgus angle decreased by 7.5 degrees in the group operated with chevron
      osteotomy and by 9.8 degrees (P 0.04) when an adductor tenotomy was added. The
      major objective factor affecting satisfaction was the attainment of a decreased
      ball circumference, shown by the fact that dissatisfied patients had a greater
      postoperative ball circumference than both satisfied and partially satisfied
      patients, whereas there were no radiographic correlations to satisfaction. We
      cannot recommend adding adductor tenotomy to the chevron osteotomy.

PMID- 7801760
TI  - Closed treatment of Jones fracture. Good results in 40 cases after 11-26 years.
AB  - 40 patients with transversal or short oblique fractures of the proximal shaft of
      the fifth metatarsal bone (Jones fracture) were treated with full weight bearing
      with or without elastic bandage in 39 cases and plaster cast immobilization in
      one. 24 cases were acute traumatic fractures, 14 stress fractures and 2
      refractures. After 17 (11-26) years, 33 of the fractures had healed primarily,
      evidence of refracture or delayed union was found in 7 and there were no non
      unions. All but one of the patients were free of symptoms.

PMID- 7801761
TI  - Maintenance of the gliding surface of tendon autografts in dogs.
AB  - To determine whether there are differences in the extent to which the superficial
      cellular layers remain viable and contribute to the healing process, extra- and
      intrasynovial hindlimb donor tendons of 12 dogs (24 tendons) were labeled with 3H
      thymidine in vitro and transferred to the medial and lateral toes of the forepaw.
      After transplantation, the distribution and amounts of remaining labeled cells
      within the healing tendon grafts were determined at 1 and 3 weeks after surgery
      by scintillation countings and autoradiographic examinations. The two types of
      tendon grafts showed different turnover rates for the elimination of labeled DNA.
      At 1 week, 25 percent of labeled DNA remained in the extrasynovial grafts and 65
      percent in the intrasynovial grafts. The two types of tendon grafts also showed
      different healing responses histologically. Autradiographic examinations showed
      that the majority of labeled cells were located in the periphery of the control
      tendons and that the numbers of labeled cells within the newly proliferated
      superficial areas of both types of tendon grafts decreased over time. These
      findings indicate that intrasynovial flexor tendons may possess improved
      prerequisites for superficial cellular survival and tendon gliding following
      autogenous tendon grafting.

PMID- 7801762
TI  - Local recurrence of soft tissue sarcoma a risk factor for late metastases. 379
      patients followed for 0.5-20 years.
AB  - We performed a retrospective analysis of 379 adult patients treated for soft
      tissue sarcoma. None had metastasis at the time of diagnosis and all were treated
      surgically. Patients who developed metastatic disease before the local recurrence
      were excluded. The 8-year metastasis-free survival rate in the group of 261
      patients with local tumor control was 0.72, compared to 0.67 in the 118 patients
      with local recurrence (P 0.2). Multiple regression analysis showed that high
      grade malignancy and large tumor size were risk factors for metastases. Local
      recurrence was not a risk factor. However, when patients with small and/or low
      grade tumors were analyzed separately, local recurrence emerged as a risk factor.
      In this group of patients, the 8-year survival rate was 0.87 for those with local
      control and 0.64 for those with local recurrence (P 0.004). Local recurrence
      appears to be a risk factor for the development of late metastases in patients
      who otherwise have a low risk of metastases.

PMID- 7801763
TI  - Healing of segmental and simple fractures in rats.
AB  - We studied the healing of segmental and simple middiaphyseal fractures in male
      Wistar rats. In one group we produced two standardized partial osteotomies with
      an 8 mm intermediary fragment in the femoral diaphysis and in the other group a
      simple partial osteotomy. The osteotomies were then manually broken, retaining
      the periosteal and muscular attachment on the medial side. The fractures were
      stabilized with a 1.6 mm steel pin, and the animals were allowed free movement.
      After 4, 8, and 12 weeks, 8 rats in each group were killed, and callus formation,
      mechanical parameters and bone blood flow were evaluated. There were no
      differences in callus production between the simple and segmental fractures
      throughout the experimental period. The mechanical parameters increased in both
      groups, and the healing patterns were the same. No differences were found in the
      total bone blood flow, but the callus blood flow in the segmental fractures was
      lower after 8 and 12 weeks than that in the simple fractures. Our findings
      indicate that closed segmental fractures treated by intramedullary nailing can
      regain strength in the same manner as simple fractures.

PMID- 7801764
TI  - Sudden hypotension and profuse bleeding during intramedullary nailing of the
      femur in cancer patients. A report of two cases.

PMID- 7801765
TI  - Uptake of dopamine by rat hepatocytes in vitro.
AB  - The present results showed that uptake of dopamine (DA) by rat isolated
      hepatocytes was mediated, in addition to simple diffusion, mainly by a
      transporter-involved process, with Km of 66.8 mumol and Vmax of 52.3 pmol.min
      1/10(5) cells. The process was pH- and temperature-dependent and required an
      activation energy of 4.12 kcal.mol-1 (Q10 = 1.25) in the range of 2.0-12.7 C and
      13.0 kcal.mol-1 (Q10 = 2.0) in the range of 12.7-39.0 C. Cysteine residue having
      free thiol group was unrelated to the activity of the transporter.
      Catecholamines, serotonin, and cocaine inhibited the DA transport, but tyramine
      (TA) and tryptamine, as well as benztropine and imipramine (which are potent
      inhibitors for hepatic TA transporter and neuronal DA transporter), had no
      inhibitory effect on the transport of DA in these cells. These results indicated
      that DA was taken up into hepatocytes by a distinct carrier. NaF and mastoparan
      influenced the transport activity in these cells further, suggesting that signal
      transducing G-proteins may be involved in the regulation of DA transporter in rat
      hepatocytes.

PMID- 7801766
TI  - Colforsin or imidazolidione potentiates cAMP elevation caused by endothelin-1 in
      rat aorta.
AB  - Endothelin-1 (ET-1) caused slow-developing and stable vasoconstrictions in
      isolated rings of rat thoracic aortae with a pD2 value of 7.55 +/- 0.10 compared
      to pD2 values of 9.30 +/- 0.10 and 8.36 +/- 0.30 for angiotensin II and
      norepinephrine, respectively. Although the potency of ET-1 was somewhat lower
      than those of norepinephrine and angiotensin II, the maximal tension generated by
      ET-1 was comparable to that of norepinephrine and considerably greater than that
      of angiotensin II. Incubation of aortic rings in the absence of extracellular
      Ca2+ or in the presence of the Ca2+ channel blocker nifedipine (100 nmol.L-1)
      greatly attenuated ET-1-induced vasoconstriction. ET-1 (20 nmol.L-1,
      approximately the ED50 for vasoconstrictions) also caused elevation of cAMP
      levels in aortic rings after 15 and 25 min of exposure. The cAMP
      phosphodiesterase inhibitor imidazolidione (Imi, Ro 20-1724, 100 mumol.L-1)
      potentiated the cAMP responses to ET-1. Rings incubated for 25 min with ET-1 (20
      nmol.L-1) showed much larger cAMP elevations caused by colforsin (Col, forskolin
      1 mumol.L-1), a direct adenylate cyclase activator and potentiator, than with Col
      or ET-1 alone. Therefore, ET-1 may utilize at least 2 signal transduction
      mechanisms, one involving the opening of nifedipine-sensitive Ca2+ channels and
      the other involving the elevation of cAMP levels, to produce the unusually slow
      developing and stable vasoconstrictions in rat aortae.

PMID- 7801767
TI  - Three drugs inhibit phospholipase A2-induced high permeability of endothelial
      monolayers.
AB  - The permeability of aortic endothelial monolayers to fluid and albumin increased
      13.5 and 16.1 times respectively after pretreatment with phospholipase A2 (PLA2,
      100 U.ml-1) for 30 min. 1-(p-Chlorobenzoyl)-5-methylindole-3-acetic acid (1.16
      mmol.L-1), SRI 63-441 (30 nmol.L-1), and 1,25-dihydroxycholecalciferol (0.1
      mumol.L-1) decreased PLA2-induced high permeability. PLA2 did not damage the
      endothelial cells significantly. Our results indicate that the action of PLA2 to
      increase the permeability of endothelial monolayers is mainly due to PLA2-induced
      lipid mediators released from endothelial cells.

PMID- 7801768
TI  - Monoclonal antibodies specific for ohmefentanyl.
AB  - Ohmefentanyl (Ohm, N[1-(beta-hydroxy-beta-phenylethyl)-3-methyl-4- piperidyl]-N
      phenylpro-pronamide), designed and synthesized by our laboratory, is a highly
      selective mu receptor agonist. After somatic cell fusion between splenocytes of
      BALB c mice, immunized by Ohm-BSA conjugate and NS-1 myeloma cells, 2 lines of
      hybridoma (D2 and F4) secreting monoclonal anti-Ohm antibodies (MAb) were
      obtained. Saturation and competition experiments showed that MAb-D2 and MAb-F4
      bound to Ohm-BSA with high affinity and high specificity. Using radioligand
      binding assay and bioassay, we also found that MAb-D2 and MAb-F4 inhibited [3H]
      Ohm binding to rat brain opioid receptors in a dose-dependent manner and
      antagonized the effect of Ohm on the contraction of guinea pig ileum induced by
      electric field stimulation. These results suggested that MAb-D2 and MAb-F4 were 2
      monoclonal antibodies specific for Ohm and could be useful as functional
      antagonists of Ohm.

PMID- 7801769
TI  - Altered alpha 1-adrenoceptor density and alpha 1A/alpha 1B ratio in rat hearts
      after propranolol treatment.
AB  - After rats were treated with propranolol (50 mg.kg-1, bid, ip) for 7 d, the
      density of alpha 1-adrenoceptors in the rat myocardial cell membranes increased
      from 137 +/- 25 to 178 +/- 30 fmol/mg protein determined by receptor radioligand
      assay. Whereas the KD value was not significantly changed, the relative
      proportion of alpha 1A-adrenoceptor subtype increased from 19 +/- 6 to 31 +/- 8%.
      The affinities of two subtypes to 5-methylurapidil were not obviously changed
      after propranolol treatment. It was suggested that alpha 1A-subtype was more
      important in alpha 1-receptor mediated alterations after beta-adrenoceptor
      blockade.

PMID- 7801770
TI  - Structure-activity relationship of memory enhancing peptide ZNC (C) PR analogs.
AB  - ZNC(C)PR has been found to be a new neuropeptide in rat brain as a significant
      enhancer of learning and memory. In this work, the structure-activity
      relationship of ZNC(C)PR was studied. First, the roles of every residue in
      ZNC(C)PR were investigated theoretically and analogs were designed according to
      the predicted conformational properties. Five analogs were synthesized following
      the design. Passive avoidance behavior tests in rats showed that NIPR, NVPR, and
      NAPR have positive effects to facilitate memory, while NSPR has no effect, and
      DLPR has somewhat inhibitory effect. As the experimental results are in good
      agreement with that of theoretical calculations, it is suggested that further
      research may help us to understand more details on the structure-activity
      relationship of ZNC(C)PR and provides a way for further design of potent agonist,
      antagonist and possible nonpeptide mimetics of ZNC(C)PR.

PMID- 7801771
TI  - Effects of low level lead exposure on behavior of young rats.
AB  - Dam rats were given Pb (0.58, 1.76, and 5.27 mmol.L-1), containing water ad lib
      from d 16 of gestation to weaning of the offspring on d 21 postpartum. The pups
      continued drinking the same water till the postnatal d 30. The neurobehavioral
      function of pups was tested. The second step-down latencies (SDL2) were shortened
      and the number of step-downs in 5 min (NSD) were increased in step-down test. The
      prolongation of the lapse of time in passing through the whole course (LTPWC) and
      the increase in number of entries into the blind alley (NEBA) were measured in
      water maze test. The number of ambulations and rearings were increased in
      locomotor activity. The results indicated that Pb exerts adverse effects on the
      learning ability and memory function, and induces hyperactivity in young rats.

PMID- 7801772
TI  - Effects of sigma and phencyclidine receptor ligands on electric field-stimulated
      rabbit ear artery constriction in vitro.
AB  - Several ligands of phencyclidine (Phe) receptors: Phe, dizocilpine maleate (Diz,
      MK-801), 1-[1-(2-thionyl)cyclohexyl] piperidine (TCP), and ligands of sigma
      (sigma) receptors: dl-N-allylnormetazocine (dl-SK&F-10047), 1, 3-di-ortho-tylyl
      guanidine (DTG), dl-pentazocine, were tested on rabbit ear arteries in vitro. It
      was found that the ligands of Phe receptors enhanced the electric field
      stimulated vasoconstriction (ESV). Their concentration-effect curves of these
      compounds were parallel in the order of potencies: Phe > Diz > TCP. The ligands
      of sigma receptors had no effect on ESV of the arteries, but 5 mumol.L-1 reduced
      or increased the effect of Phe (5 mumol.L-1) on ESV. d-SK&F-10047, d-pentazocine,
      and DTG inhibited the effect of Phe on ESV from 364 +/- 22 mg to 142 +/- 49 mg (n
      = 5, P < 0.01), 262 +/- 95 mg (n = 5, P < 0.05), and 291 +/- 80 mg (n = 5, P >
      0.05), respectively. The levoisomers: l-SK&F-10047 and l-pentazocine enhanced the
      effect of Phe on ESV from 364 +/- 22 mg to 484 +/- 78 mg (n = 5, P < 0.05), and
      466 +/- 95 mg (n = 5, P < 0.05), respectively. These results revealed that there
      were mainly Phe receptors but hardly any sigma receptors in the arteries.

PMID- 7801773
TI  - Effects of inhibitor of endothelium-derived relaxing factor on hypoxic
      contraction of isolated pig coronary artery.
AB  - Exposure of isolated pig coronary artery with endothelium intact to hypoxia Krebs
      Henseleit solution aerated with 95% N2 + 5% CO2 caused a transient contractile
      response, and the coronary artery without endothelium exhibited a gradual
      decrease in basal tension. The endothelium-dependent contractile response to
      hypoxia was almost completely blocked by nitro-L-arginine (0.2 mmol.L-1), and
      inhibited by methylthioninium chloride (10 mumol.L-1). The inhibitory effect of
      the NLA was partially reversed by L-arginine (2 mmol.L-1). Sodium nitroprusside
      (10 mumol.L-1) was also completely antagonized and nicorandil (0.3 mol.L-1)
      remarkably reduced the hypoxic contractile response. Tetraethylammonium (10
      mmol.L-1) and glibenclamide (1 mumol.L-1) had little effect on hypoxia-induced
      vascular contraction, whereas cromakalim (1 mumol.L-1) produced obvious relaxing
      effect on hypoxic response. These results suggest that suppression of basally
      released nitric oxide (NO) is an important mechanism of coronary vasoconstriction
      induced by hypoxia.

PMID- 7801774
TI  - Effects of m-nisoldipine on contraction and 45Ca influx in isolated rat aorta.
AB  - m-Nisoldipine caused a concentration-dependent depression of the contractile
      response and 45Ca influx evoked by KCl in isolated rat thoracic aorta. The IC50
      value for contraction and 45Ca influx were 0.69 (95% confidence limits 0.32-1.5)
      nmol.L-1 and 0.35 (95% confidence limits 0.06-2.0) nmol.L-1, respectively. There
      was a positive correlation between the inhibition of KCl-evoked contraction and
      45Ca influx (r = 0.996). m-Nisoldipine (0.1-10 mumol.L-1) did not influence the
      45Ca influx into resting cells and failed to inhibit noradrenaline (1.0 mumol.L
      1)-evoked contraction and 45Ca influx. The results suggest that the relaxant
      effect of m-nisoldipine on rat aorta may be closely related to the blockade of
      Ca2+ entry through a potential-dependent calcium channel.

PMID- 7801775
TI  - Cardiac responses activated by nicotine in canine ganglial plexus between aorta
      and pulmonary artery.
AB  - In order to study the location and function of nicotine-sensitive neurons of
      cardiac ganglial plexuses, microdissections of collections of fat pads were
      carried out, and nicotine (100 micrograms) was injected into the ganglial plexus
      between aorta and pulmonary artery (A-PGP) in 30 anesthetized open-chest dogs.
      There were numerous ganglia or neurons in A-PGP. Either positive or negative
      inotropic and chronotropic responses were elicited following injections of
      nicotine into A-PGP. Control injections of 0.1 ml saline into A-PGP and
      injections of nicotine (100 or 200 micrograms) into right marginal ganglial
      plexus did not elicit any cardiac responses. After acute decentralization,
      nicotine (100 micrograms) was again injected into the same locus of A-PGP. Some
      positive and negative responses could still be induced, but their frequencies
      were reduced. These suggest that nicotine can directly activate the efferent
      parasympathetic and sympathetic neurons and indirectly activate them by
      stimulating the afferent neurons existing on the surface of dog heart.

PMID- 7801776
TI  - Identification of beta-adrenoceptors in mouse myometrium by radioligand binding
      study.
AB  - The binding of radioligand to cell membrane prepared from mouse myometrium was
      used to identify the characteristics of beta-adrenoceptors. Uteri were taken from
      mature mice (Kunming Strain) weighing 40 +/- 5 g pretreated with estradiol
      benzoate 1 mg.kg-1.d-1 ip for 2 d. The binding of [3H]dihydroalprenolol ([3H]DHA)
      to uterine membrane was saturable, having a Bmax of 378 fmol/mg protein and a KD
      of 3.1 nmol.L-1. The slope of Hill plot (nH = 1.03) indicated the absence of
      cooperative interactions. IC50 and K1 values of l-norepinephrine (NE), dl
      propranol (Pro), d-timolol (d-Tim), and l-Tim competed for the [3H]DHA binding
      sites were 171 +/- 10, 10.3 +/- 4.3, 6.5 +/- 2.1, 0.40 +/- 0.23 nmol.L-1 and 113
      +/- 6, 6.3 +/- 2.8, 4.0 +/- 1.3, 0.25 +/- 0.14 nmol.L-1, respectively. These 4
      agents competed for the [3H]DHA binding sites in an order of potency: l-Tim > d
      Tim > Pro > NE. Atenolol (Ate) did not compete for [3H]DHA binding sites. The
      results suggested that these binding sites for [3H]DHA in mouse myometrium
      appeared to be beta 2-adrenoceptor.

PMID- 7801777
TI  - Effect of procainamide on platelet adhesion in rats.
AB  - Effect of procainamide on platelet adhesion in rats was studied with the improved
      rotating glass sphere method. Procainamide of 136.0, 34.0, 8.5 mumol.L-1 in vitro
      and 10 mg.kg-1 in vivo inhibited significantly the platelet adhesion with the
      inhibitory rates of 56%, 28%, 8%, and 24%, respectively. It showed that
      procainamide given in vitro or in vivo produced an inhibition on platelet
      adhesion.

PMID- 7801778
TI  - Electrophysiologic effects of total flavones of Hippophae rhamnoides L on guinea
      pig papillary muscles and cultured rat myocardial cells.
AB  - The effects of total flavones of Hippophae rhamnoides L (TFH) were evaluated
      using conventional microelectrode technic. After administration of TFH 100-200
      mg.L-1, the action potential duration of 50% repolarization (APD50) was shortened
      both in cultured rat myocardial cells and in guinea pig papillary muscles. The
      slope of phase 4 of depolarization (SP4) in cultured rat myocardial cells was
      decreased and the contractile force (CF) in guinea pig papillary muscles was
      weakened. Arrhythmias evoked by strophantin G in guinea pig papillary muscles
      were suppressed by TFH 100 mg.L-1. These findings suggested that the influence of
      TFH on myocardial cells may be resulted mainly from its inhibition of Ca2+ influx
      and its interference with intracellular Ca2+ reservoir.

PMID- 7801779
TI  - Effects of Panax notoginseng saponins on myocardial adenosinetriphosphatase.
AB  - Effects of total Panax notoginseng saponins (PNS) and Panax notoginseng saponin
      monomers Rb1 and Rg1 (Rb1, Rg1) on total ATPase and Na(+)-K(+)-exchanging ATPase
      of guinea pig heart were studied. It was found that PNS inhibited the total
      myocardial ATPase, but had no significant effect on the myocardial Na(+)-K(+)
      exchanging ATPase. The total ATPase was inhibited by Rg1, and more clearly by
      Rb1. The automaticity and contractility of isolated guinea pig atria were
      inhibited by Rb1. Rg1 decreased the spontaneous frequency of isolated guinea pig
      right atrium, but not markedly the contractility of the left atrium. These
      results demonstrate that Rb1 is the main ingredient in PNS.

PMID- 7801780
TI  - [Mechanism of scavenging effects of (-)-epigallocatechin gallate on active oxygen
      free radicals].
AB  - The concentration of 50% scavenging ratio (SC50) and the scavenging rate
      constants (k) and stiochiometric factor (n) were determined when (-)
      epigallocatechin gallate [(-)-EGCG] scavenging superoxide anion free radical (O2.
      ) and hydroxyl radical (.OH). The mechanism of scavenging active free radicals of
      (-)-EGCG and the promotion of (-)-EGCG free radical and its structure were
      analyzed in vitro. Our results suggest that the centers of scavenging reaction of
      (-)-EGCG are B, D, and A cycles, and each (-)-EGCG traps six O2.- or .OH. It is
      in accord with the value of stiochiometric factor n = 6.

PMID- 7801781
TI  - [Lithium-induced norepinephrine release from hippocampal slices in the absence of
      extracellular Ca2+].
AB  - Slices of rat hippocampus, preincubated with [3H] norepinephrine ([3H]NE) were
      superfused with Ca(2+)-free medium containing desipramine 1 mumol.L-1, Li+ (40-80
      mmol.L-1) evoked [3H]NE release in a concentration dependent manner. It was
      enhanced by 4 beta-phorbol 12,13-dibutyrate (PDB) and inhibited by tetrodotoxin.
      Ca(2+)-chelator BAPTA-AM did not attenuate this Li-evoked [3H]NE release. After
      application of 3,4-diaminopyridine to evoke [3H]NE release and PDB to enhance
      this release, the Li(+)-evoked [3H]NE release was significantly inhibited. The
      findings suggest that the liberation of internal Ca2+ stores was not involved in
      this release process.

PMID- 7801782
TI  - [Therapy of experimental autoimmune myasthenia gravis in rabbits with 4
      aminopyridine and 3,4-diaminopyridine].
AB  - The autoimmune myasthenia gravis (AMG) in rabbits was produced by intradermal
      injection of N-AChR-rich membrane vesicles isolated from the electric organ of
      Narcine limlei. After i.v. 4-aminopyridine (4-AP) 0.8 mg.kg-1 to 8 AMG rabbits,
      their general posture improved promptly, the features of gastrocnemius compound
      action potentials and toe twitches elicited by 4-Hz stimuli applied to the
      sciatic nerve returned to normal, and the tetanic plateau evoked by 50-Hz
      indirect stimulation was again well sustained. This improved condition lasted 9.1
      +/- 2.5 h. Other 8 AMG rabbits given 3,4-diaminopyridine (3,4-DAP) 0.4 mg.kg-1
      showed a similar improvement for 9.3 +/- 3.1 h. These results indicated that 4-AP
      and 3,4-DAP were effective in treating the AMG in rabbits, they may be useful in
      the clinical treatment of myasthenia gravis patients.

PMID- 7801783
TI  - [Influence of endothelin-1 on ventricular fibrillation threshold in acute
      myocardial ischemic rats].
AB  - The influence of endothelin-1 on ventricular fibrillation threshold was studied
      in acute myocardial ischemic rats. Endothelin-1 (1.5-3.0 micrograms.kg-1 i.v.)
      given 5 min before ischemia reduced the ventricular fibrillation threshold in a
      dose- and time-dependent manner. Its effect lasted at least 60 min. A marked
      increase of spontaneous ventricular tachycardia and myocardial infarct size was
      seen and the arterial blood pressure was at a higher level (18.5-20.1/14.4-15.8
      kPa) after 3.0 micrograms.kg-1. Diltiazem prevented partially from reduction of
      ventricular fibrillation threshold, eliminated completely the vasopressor
      response and limited the extension of myocardial necrosis induced by endothelin
      1.

PMID- 7801784
TI  - [Effect of protopine on rabbit platelet function].
AB  - Protopine (Pro) inhibited dose-dependently rabbit platelet aggregation induced by
      ADP, arachidonic acid (AA), collagen, or aggregoserpentin of Trimeresurus
      mucrosquamatus venom (TMVA) in vitro. Their IC50 were 25.3, 30.5, 46.9, 33.4
      mumol.L-1, respectively. Pro 10, 20 mg.kg-1 iv also inhibited the platelet
      aggregation induced by these inducers. The effects (maximal at 5 min) lasted 1 h.
      By using fluorophotometry and RIA, it was seen that Pro suppressed the release of
      5-HT from platelets during aggregation induced by collagen, AA, or TMVM in vitro.
      Pro did not block the formation of thromboxane A2 during aggregation induced by
      AA and did not increase the content of cAMP in rabbit platelet, but increased the
      content of cGMP in rabbit platelets. The antiplatelet effect of Pro may be
      related to an increase cGMP in rabbit platelets and the suppression of the
      release of the active substances from platelets.

PMID- 7801785
TI  - [Effect of total coumarins from dried fruits of Cnidium monnieri on
      glucocorticoid-induced osteoporosis in rats].
AB  - Twenty-four 3-month-old male SD rats were divided into 3 groups: Group 1--control
      (ig water). Group 2--ig prednisone 45 micrograms.kg-1 twice a week. Group 3-
      treated with total coumarins of dried fruits of Cnidium monnieri (L) Cuss (TCCM)
      and prednisone. TCCM was given ig 5 g.kg-1, 6 days per week. After 90 d, rats
      were killed. The proximal tibiae of rats were processed undecalcified for
      histomorphometric analysis. In comparison with control rats, the bone resorption
      was enhanced and bone formation decreased. The trabecular bone areas were
      characterized by reduction of 40% in rats which received prednisone. Trabecular
      bone areas of rats treated with TCCM increased 56% compared with rats receiving
      prednisone. All indices of bone histomorphometry were near to those in the
      control. The results showed that TCCM prevented glucocorticoid-induced
      osteoporosis.

PMID- 7801786
TI  - [Protective effect of captopril on cultured rat myocardial cells with anoxia and
      reoxygenation injury].
AB  - The effect of captopril (Cap) on electric activity of cultured rat myocardial
      cells under anoxia and reoxygenation was studied with standard microelectrode
      techniques. Results showed that anoxic solution caused lowerings of MDP, APA, and
      Vmax, and a shortening of APD50. All myocytes revealed multiform arrhythmias, and
      most cells stopped beating within 30 min, while only 40% of the cells exhibited
      arrhythmias but none stopped beating in the presence of 40 mg.L-1 under the same
      condition. During reoxygenation, most cells resumed beating in 10 min but some of
      these cells stopped beating again. The electric activities in rebeating cells
      during reoxygenation for 30 min were lower than those in normoxic cells. Cap (40
      mg.L-1)-treated cells rebeat quickly after reoxygenation and no cell stopped
      beating any more, with parameters higher than those in untreated cells. These
      results demonstrate that Cap yields some beneficial effects on preventing anoxia
      and reoxygenation injury in cultured rat myocardial cells.

PMID- 7801787
TI  - [Effect of dimercaptosuccinic acid per os on distribution and excretion of 210Pb
      and 203Hg in mice].
AB  - Sodium dimercaptosuccinate (Na-DMS) ip 1 g.kg-1, dimercaptosuccinic acid (DMSA)
      ig 1 g.kg-1, DMSA ig 1 g.kg-1 with NaHCO3 or Na-citrate ig 3 g.kg-1 was given to
      mice, separately. It enhanced the excretion of 210Pb in urine about 3.4, 3.8,
      3.6, and 2.3 times vs control, respectively within 24 h. It enhanced the
      excretion of 203Hg in urine about 2.4, 2.3, 3.3, and 2.7 times, respectively
      within 24 h. Fecal excretion was not significantly elevated vs control. Tissue
      radioactivities showed a remarkable decrease in the levels of 210Pb and 203Hg in
      most organs, but DMSA increase the 210Pb content in kidney. The therapeutic
      effect of ig DMSA was similar to that of ip sodium dimercaptosuccinate.

PMID- 7801788
TI  - Eye-pineal relationships. International symposium. 21-25 September 1994, Lodz,
      Poland. Proceedings and abstracts.

PMID- 7801789
TI  - Pineal photosensitivity. A comparison with retinal photoreception.
AB  - Pineal photoreceptors of poikilothermic vertebrates possess numerous anatomical,
      physiological and biochemical similarities to retinal photoreceptors, including
      the rhythmic melatonin biosynthesis, with nocturnal peaks and low day-time
      levels. This brief outline will survey the photoreceptor properties of the pineal
      organ of poikilothermic vertebrates, which suggest that the pineal is not only a
      simple light detector (that acts as a kind of photometer), but that it is capable
      of processing the light information and to discriminate it from informations that
      have no meaning for its assumed photoperiodic function.

PMID- 7801790
TI  - Pineal function during aging: attenuation of the melatonin rhythm and its
      neurobiological consequences.
AB  - The pineal hormone melatonin is a potent free radical scavenger. In particular,
      it quenches what is generally considered the most toxic and damaging free radical
      produced in the organism, the hydroxyl radical (.OH). Melatonin production in the
      pineal gland declines progressively with age such that in old animals and elderly
      humans the levels of melatonin available to the organism are a fraction of that
      of young individuals. A prominent theory of aging claims that the anatomical and
      functional degeneration that organs undergo during aging is a consequence of
      accumulated free radical damage. This being so, melatonin may well play a
      significant role in aging processes. If the drop in melatonin which normally
      occurs as animals age could be prevented, perhaps the aging process would also be
      delayed. Also, supplemental administration of melatonin may be beneficial in
      delaying age-related degenerative conditions. Certainly, free radical damage has
      been implicated in a number of neurodegenerative disorders. Theoretically,
      melatonin administration may forestall these as well.

PMID- 7801791
TI  - Regulation of hydroxyindole-O-methyltransferase gene expression in the pineal
      gland and retina.
AB  - Hydroxyindole-O-methyltransferase (HIOMT) catalyzes the final step of melatonin
      biosynthesis and appears to be specifically expressed in the pineal gland and in
      the retina. This review deals with the regulation of HIOMT by environmental light
      and with the developmental aspects of HIOMT expression in chicken and rat. Early
      studies based on HIOMT activity measurements and more recent studies involving
      cDNA hybridization to HIOMT mRNA are taken into consideration. Together, the data
      reveal that long term regulation of HIOMT by light would rely on a day/night
      rhythm of HIOMT gene transcription, coupled to a slow turnover of the protein.
      Rapid changes in HIOMT mRNA levels and early expression during embryonic
      development suggest that further studies on this gene may shed light on the
      molecular mechanisms involved in the differentiation of the melatoninergic
      function and in its regulation by light, both in the pineal gland and in the
      retina.

PMID- 7801793
TI  - Serotonin and melatonin in the iris/ciliary processes and their involvement in
      intraocular pressure.
AB  - From the evidence available it is clear that melatonin and serotonin receptors
      exist in the iris/ciliary processes of the rabbit. These receptors may be
      involved in maintaining the intraocular pressure (IOP). However, the published
      results on this point are often contradictory, perhaps because of the variation
      in the species of animals used and the methodology employed. It is also clear
      that the data obtained from studies on the rabbit cannot be directly applied to
      man. Nevertheless, present information points to the possibility that drugs
      influencing specific serotonin and/or melatonin receptors may be used to
      influence IOP in man and thus have a therapeutic effect.

PMID- 7801792
TI  - The role of dopamine in the regulation of melatonin biosynthesis in vertebrate
      retina.
AB  - The vertebrate retina rhythmically synthesizes melatonin, a hormone involved in
      the regulation of several intraocular processes cued by environmental lighting
      conditions. The rhythm of retinal melatonin production, with maximal synthesis at
      night in darkness, is driven by the photoperiodic environment to which animals
      are exposed, and is generated by an endogenous circadian clock(s). This article
      reviews data on the role of dopamine, an established retinal neurotransmitter and
      paracrine factor, as a mediator of acute suppressive and entrainment action of
      light on the melatonin generating system in the retina. Special emphasis is given
      to the characterization of dopamine receptor types involved in the control of
      retinal melatonin formation.

PMID- 7801795
TI  - Actin. Biophysics, biochemistry, and cell biology. Troy, New York, August 5-9,
      1992. Proceedings of an international conference.

PMID- 7801794
TI  - Histamine in the central nervous system: its role in circadian rhythmicity.
AB  - Histamine is an accepted neurotransmitter and/or neuromodulator in the central
      nervous system (CNS). Its neuronal system in the brain is well organized, with
      cell bodies localized in a small area of the posterior hypothalamus. Diverse
      biological actions of histamine are mediated via three classes of receptors
      termed H1, H2, and H3. The existence of other histamine receptor subtypes is
      likely in invertebrates or in birds. This article surveys basic data indicative
      of a neuroregulator role of histamine in the CNS; it also presents accumulating
      evidence suggesting that histamine may be related to circadian rhythmicity in the
      body.

PMID- 7801796
TI  - Actin regulation and surface catalysis.

PMID- 7801797
TI  - Caldesmon: possible functions in microfilament reorganization during mitosis and
      cell transformation.

PMID- 7801798
TI  - Cytoskeleton, motile structures and macromolecular crowding.

PMID- 7801799
TI  - Combining electron microscopy and X-ray crystallography data to study the
      structure of F-actin and its implications for thin-filament regulation in muscle.
AB  - The convergence of structures, all determined by independent global searches and
      subsequent refinement on different electron microscopy data sets, with the X-ray
      fiber diffraction results strongly suggests that we now have the approximately
      correct structure for F-actin. This consensus structure will now provide a
      reliable, well-defined platform upon which to study the structure and function of
      proteins bound to actin. Among these are capping proteins, such as severin and
      gelsolin, contractile proteins, such as myosin and its subfragments, and proteins
      involved in regulation, such as troponin and tropomyosin.

PMID- 7801800
TI  - Actin filament dynamics in cell motility.

PMID- 7801801
TI  - Changes in adhesion plaque protein levels regulate cell motility and
      tumorigenicity.

PMID- 7801802
TI  - Induction of collagen synthesis in response to adhesion and TGF beta is dependent
      on the actin-containing cytoskeleton.

PMID- 7801803
TI  - Gelsolin expression in normal human keratinocytes is a function of induced
      differentiation.

PMID- 7801804
TI  - Actin filaments and the spatial positioning of mRNAS.

PMID- 7801805
TI  - Redistribution of p52(PAI-1) mRNA to the cytoskeletal framework accompanies
      increased p52(PAI-1) expression in cytochalasin D-stimulated rat kidney cells.

PMID- 7801806
TI  - Brush border myosin I has a calmodulin/phosphatidylserine switch and tail actin
      binding.

PMID- 7801807
TI  - Control of p52(PAI-1) gene expression in normal and transformed rat kidney cells:
      relationship between p52(PAI-1) induction and actin cytoarchitecture.

PMID- 7801808
TI  - Evidence for an F-actin like conformation in the actin:DNase I complex.
AB  - We demonstrate that a ribose modified analogue of ATP, TNP-ATP, can exchange with
      a resident nucleotide in F-actin, but fails to bind to G-actin. TNP-ATP is also
      able to bind to actin in the actin:DNase I complex, suggesting that the
      nucleotide binding site in the actin:DNase I complex adopts a conformation
      similar to that found in F-actin. This result is consistent with the hypothesis
      that the two major domains of actin on either side of the cleft are able to
      "flex" or move relative to each other in G-actin, but that this flexing motion is
      limited as a consequence of either polymerisation or DNase I binding. F-actin, in
      which approximately 80% of the bound nucleotide is TNP-ADP, appears to be
      functionally similar to native ADP-F-actin. It can superprecipitate with myosin
      and, following regulation with troponin-tropomyosin, exhibits a Ca(2+)
      sensitivity during superprecipitation. Sonication induced nucleotide exchange in
      regulated F-actin was not sensitive to the presence of Ca2+ which argues against
      a significant conformational change in the vicinity of the nucleotide binding
      site during Ca(2+)-sensitive thin filament regulation.

PMID- 7801809
TI  - Vibrational modes of G-actin.

PMID- 7801810
TI  - Actin-bound nucleotide/divalent cation interactions.
AB  - At this point, it may be worthwhile to list, in summary form, the important
      aspects of divalent cation and nucleotide binding to actin that have been
      reviewed here: 1) High affinity divalent cation binding to actin is very tight,
      with equilibrium dissociation constant KCa approximately 1 nM and KMg
      approximately 5 nM at pH 7.0. 2) The binding kinetics of Ca++ are diffusion
      limited. Dissociation is slow, with k-Ca approximately 0.015 sec at pH 7.0 (and
      low ionic strength). 3) The binding kinetics of Mg++ are limited by the
      characteristics of the Mg++ aquo-ion and are much slower than for Ca++; k-Mg
      approximately 0.0012 at pH 7.0. 4) Increase in pH or ionic strength weakens
      divalent cation binding at the high affinity site, primarily by increasing k-Ca
      and k-Mg. 5) Exchange of Mg++ for Ca++ (or vice versa) at the high affinity site
      is by a competitive pseudo-first order process with an apparent rate constant
      (kapp) intermediate between k-Ca and k-Mg and dependent upon the cation
      concentration ratio [Ca]/[Mg] present. 6) High affinity ATP binding is modulated
      by the high affinity divalent cation. The cation concentration range over which
      this modulation occurs is about 100-fold higher for Mg++ than for Ca++, again
      because of the different characteristics of the Mg++ and Ca++ aquo-ions. 7) At
      low divalent cation concentrations, ATP dissociation from actin is limited by
      dissociation of the tightly-bound divalent cation. 8) At high divalent cation
      concentrations, ATP dissociation probably occurs via dissociation of the divalent
      cation-nucleotide complex and is quite slow, with dissociation rate constant
      approximately 0.0005 sec-1. 9) Competitive nucleotide exchange on actin may be
      described by a pseudo-first order model analogous to that for divalent cation
      exchange. The pseudo-first order rate constants depend upon the divalent cation
      concentration. The overall nucleotide exchange rate constant kex depends upon
      these constants and the solution nucleotide concentration ratio, e.g.
      [ATP]/[ADP]. The following circumstances develop from the characteristics of the
      high affinity binding of divalent cation and nucleotide to actin: 1) The standard
      methods for actin preparation convert in vivo Mg-actin into Ca-actin. 2)
      Converting Ca-actin back to Mg-actin is not easy. A very low ratio of [Ca]/[Mg]
      is necessary, which usually requires the use of Ca-cheltors, and a long time (5
      10 min) must be allowed for complete exchange.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7801811
TI  - Influence of the high affinity divalent cation on actin tryptophan fluorescence.
AB  - This study demonstrates that the intrinsic tryptophan fluorescence of actin
      provides an effective and convenient way of measuring divalent cation exchange
      and polymerization of native actin. In the measurement of divalent cation
      exchange, this method is as sensitive as those previously used (8) and provides
      further evidence of the importance of the tightly bound divalent cation to the
      properties of actin. In monitoring polymerization, this method cannot compete
      with the sensitivity of the commonly used pyrene-actin fluorescence. However,
      some proteins (e.g., profilin) and other agents (e.g., cytochalasin D) that bind
      to actin are affected by the presence of fluorescent labels, making actin
      intrinsic fluorescence potentially useful in investigating the interaction of
      these agents with actin, and in validating data obtained using labeled actin. Our
      laboratory routinely checks the quality of our native actin preparations using
      this technique and, more recently, we have used actin tryptophan fluorescence to
      monitor the nucleating and severing effects of gelsolin on actin. The simplicity
      of the technique is most appealing, and we expect that a variety of innovative
      and routine uses will be developed.

PMID- 7801812
TI  - C-terminus on actin: spectroscopic and immunochemical examination of its role in
      actomyosin interactions.

PMID- 7801813
TI  - Actin polymerization: regulation by divalent metal ion and nucleotide binding,
      ATP hydrolysis and binding of myosin.
AB  - Actin filaments are major dynamic components of the cytoskeleton of eukaryotic
      cells. Assembly of filaments from monomeric actin occurs with expenditure of
      energy, the tightly bound ATP being irreversibly hydrolyzed during
      polymerization. This dissipation of energy perturbs the laws of reversible
      helical polymerization defined by Oosawa and Asakura (1975), and affects the
      dynamics of actin filaments. We have shown that ATP hydrolysis destabilizes actin
      actin interactions in the filament. The destabilization is linked to the
      liberation of Pi that follows cleavage of gamma-phosphate. Pi release therefore
      plays the role of a conformational switch. Because ATP hydrolysis is uncoupled
      from polymerization, the nucleotide content of the filaments changes during the
      polymerization process, and filaments grow with a stabilizing "cap" of terminal
      ADP-Pi subunits. The fact that the dynamic properties of F-actin are affected by
      ATP hydrolysis results in a non-linear dependence of the rate of filament
      elongation on monomer concentration. Possible modes of regulation of filament
      assembly may be anticipated from the basic properties of actin. We have shown
      that the tightly bound divalent metal ion (Ca2+ or Mg2+) interacts with the beta-
      and gamma-phosphates of ATP bound to actin, and that the Me-ATP bidentate chelate
      is bound to G-actin in the A configuration. The nature of the bound metal ion
      affects the conformation of actin and the rate of ATP hydrolysis. In motile
      living cells, a large pool of actin is maintained unpolymerized by interaction
      with G-actin binding proteins such as thymosin beta 4 and its variants or
      profilin. Part of this pool is released to increase the F-actin pool upon cell
      stimulation. The role of G-actin polymerizing proteins may be crucial in defining
      the patterns of filament assembly in these situations. The myosin head (myosin
      subfragment-1) may be considered as a model actin polymerizing protein, may be
      the closest model to the short tailed myosin I family. The mechanism of assembly
      of decorated filaments from G-actin and myosin subfragment-1 has therefore been
      examined.

PMID- 7801814
TI  - Structural requirements of tropomyosin for binding to filamentous actin.

PMID- 7801815
TI  - Actin-gelsolin interaction.

PMID- 7801816
TI  - [Amputation injuries of large extremity segments. Clinical management].
AB  - Amputating injuries are often combined with multiple trauma. The management of
      these serious traumas has to consider survival more than restoration of function
      and extremity preservation. Out of 51 patients with 60 macroamputation injuries
      only one case was successful in replantation. The leading rule in the treatment
      of macroamputation still must be life before limb, as our series of the years
      1988 up to 1991 clearly shows.

PMID- 7801817
TI  - [Prosthetic management after amputation injuries of the lower extremities.
      Orthopedic-technical management].
AB  - The primary treatment of a below and above knee amputation consists in replacing
      the lost extremity with a preliminary prosthesis. This has been of value
      regarding the medical-social rehabilitation and treatment costs. The final
      prosthesis in form of a full contact or short stem prosthesis in below knee
      amputations means extraordinary good comfort to the patient and should be
      preferred to the "classic" below knee prosthesis with thigh stem. In the last
      years the final prosthetic design for above knee amputation has changed from the
      classic transversal-oval form to the longitudinal-oval CAT-CAM-stem. The
      distinctive advantages of this design is a physiological weight bearing of the
      hip joint and no risk of compression of the medial vessels.

PMID- 7801818
TI  - [Preserving the length of amputation stumps by microvascular flap transfer of the
      lower extremity].
AB  - With different case reports we want to show the role of microvascular tissue
      transfer in preservation of lower extremity amputation length. To salvage
      amputation stumps after traumatic amputation, as well as in case of chronic soft
      tissue problems after amputation, the radialis forearm flap is preferred for
      smaller defects, for example after transmetatarsal amputation, whereas with the
      latissimus dorsi muscle flap bigger areas can be reconstructed. But also the
      tensor fascia latae flap and the scapular flap can be used for soft tissue
      reconstruction. With microvascular soft tissue transfer amputation stump length
      can be preserved in order to have a better functional outcome, especially for
      prosthetic rehabilitation.

PMID- 7801819
TI  - [Indications, technique and results of muscle flaps in decubitus ulcers of the
      pelvic region in paraplegic patients].
AB  - Over a period of 10 years 57 pelvic pressure sores of 47 para- and tetraplegic
      patients were covered operatively with a muscle flap at the Co-Operative Trade
      Association Hospital for Accidents, at Tubingen, Germany. 39 patients with 49
      muscle flap-covered decubiti were seen in a follow-up examination. Despite many
      postoperative complications--not uncommon for septic patients--there was a high
      rate of complete healing (94%) of the pressure sores within a short period of
      rehabilitation. Indeed one cannot prove the superiority of the muscle flaps over
      cutaneous and fasciocutaneous flaps because of the missing statistical
      comparability and correlation capability of the results with other studies. In
      our opinion muscle flaps in the pelvic area seem to be advantageous to cutaneous
      and fasciocutaneous flaps.

PMID- 7801820
TI  - [C-reactive protein as infection parameter in clinically suspected postoperative
      infection after trauma surgery and orthopedic interventions. 2].
AB  - Prospectively the levels of C-reactive protein (CRP) of 40 patients were studied
      twice within 6-12 hours in case of a suspected infection after different
      osteosynthetic and orthopedic procedures and compared with the levels of the
      erythrocyte sedimentation rate (ESR). 16 patients showed an increase of CRP in
      relation to a wound infection, hematoma or effusion in all but one case. 6
      patients showed an increase of ESR, which also could be cleared in all but one
      case. Those patients with a proved wound infection demonstrated a CRP-rise in 8
      cases, a CRP-plateau in 4 cases and no CRP-decrease. The same patients showed an
      ESR-rise in 3, an ESR-plateau in 7 and an ESR-decrease in even 2 cases. This
      study indicates that the determination of two CRP-levels with a short interval in
      case of a clinically suspected infection is another, meaningful criterion in
      making a decision for an operative revision.

PMID- 7801821
TI  - [Ultrasound diagnosis in disorders of the neuromuscular knee joint system after
      cruciate ligament injuries].
AB  - To verify neuromuscular disorders caused by joint alteration often technically
      measuring methods have to be applied which are complicated to discuss (isokinetic
      measuring methods, EMG etc.). Therefore the monitoring of limb circumference
      values has become established in practice. This study confronts the circumference
      measuring for the thigh following damages resp. injuries in the knee joint with
      direct methods to determine the muscular cross-sectional area. It is shown that
      circumference measures only up to a point can answer questions on muscular
      hypertonia and atrophy. The study presents standardized sonographic measuring
      methods that make possible an objective and reproducible verification of the
      state of individual muscles. Additionally the study shows that the m. vastus
      intermedius is to a much higher degree afflicted by neuromuscular disorders of
      knee joint damages resp. injuries than assumed until now.

PMID- 7801822
TI  - [Expert assessment of the rotator cuff defect: a case report with general
      administrative references].

PMID- 7801823
TI  - [Muscle rupture--combined with rupture of the fibular ligament].

PMID- 7801824
TI  - Psychopharmacology in the medically ill. General principles.

PMID- 7801825
TI  - Treatment of mania in the medically ill.

PMID- 7801826
TI  - Use of psychotropic agents in patients with heart disease.

PMID- 7801828
TI  - Use of psychotropic medication in the neurologically ill.

PMID- 7801827
TI  - Psychotropic medications in gastrointestinal and hepatic disease.

PMID- 7801829
TI  - Psychotropic medications and the skin.

PMID- 7801830
TI  - Cellular energetics during exercise.
AB  - How is the muscle fiber designed to accomplish the diversity of tasks performed
      by striated muscle? Basically, a common contractile mechanism and a similar
      organization of metabolism in striated muscles are used to generate a wide
      spectrum of speeds and durations of contraction. The speed of contraction ranges
      from manyfold within an animal to over a hundred-fold between animals, owing to
      variation in the intrinsic velocities of the myosin isoforms. Recruiting fibers
      that contain the myosin isoform that contracts at the appropriate velocity varies
      the speed of locomotion at minimal cost. The magnitude and duration of the energy
      supply required to meet this contractile demand depends on the size of the
      cellular energy buffer and the capacities of the metabolic pathways. The faster
      the contractile speed, the larger the PCr pool and the greater the glycolytic
      capacity to meet a high rate of ATP use. Slower-contracting fibers have a smaller
      buffer for the short term, but an increased oxidative capacity for continuous
      energy supply to maintain energy balance over the long term. In general, fibers
      trade contractile speed for duration of performance, but a number of exceptions
      exist where rapid contractions are maintained for extended periods. In the face
      of this heterogeneity of properties, common features are found that assure an
      energy balance. The PCr/ATP buffer system offers a simple mechanism of feedback
      control of energy supply despite the wide range of high-energy phosphate
      concentrations and oxidative capacities found in skeletal muscle. An oxygen
      balance system also appears to be present in the terminal structures of the
      respiratory system, the capillaries, and mitochondria. Despite the diversity of
      these structures, a rather constant ratio of oxygen delivery capacity to
      mitochondrial oxidative capacity is found in vertebrate striated muscles.
      Finally, a critical feature of muscle energy balance that remains unresolved is
      (are) the mechanism(s) controlling mitochondrial respiration in heart. Feedback
      control appears to account for linking ATP supply to demand in skeletal muscle,
      but the mechanisms governing respiratory control in heart are still under
      vigorous investigation. Thus, the links between contractile demand and oxidative
      phosphorylation are still unresolved in this tissue, which may indicate that a
      key element is missing in our understanding of the cellular energetics of
      exercise.

PMID- 7801831
TI  - The mechanical design of the muscular system.

PMID- 7801832
TI  - Relating mechanics and energetics during exercise.

PMID- 7801833
TI  - Circulatory function during exercise: integration of convection and diffusion.
AB  - The cardiovascular system has frequently been hypothesized to be the limiting
      step for O2 transport that determines VO2 max in many species of mammals. Careful
      analysis of the factors that determine how O2 is transported by the circulation
      demonstrate that such a single-step limitation cannot exist. Evaluation of the
      results of experiments in which circulatory O2 transport capacity was
      experimentally altered demonstrates no direct or absolute relationship between
      changes in O2 transport capacity and changes in VO2 max. Furthermore,
      experimental evidence collected during maximal exercise in hypoxia and hyperoxia
      supports the concept that multiple components of the O2 transport system
      contribute to limiting O2 flux at VO2 max. Consideration of the basic equations
      that describe O2 transport through the respiratory system shows that changes in
      PO2 at each step of the system required to increase O2 flux through that step
      conflict with the changes in PO2 required to increase flux through adjacent
      steps. Changes in convection, capacitance, or conductance at one step affect gas
      transport through the adjacent steps. Hence, no single-step limitation to O2
      transport is possible, because the convective and diffusive gas exchangers are
      interdependent. Increasing QT at VO2 max always increases O2 flux (although not
      necessarily in proportion to the increase in QT), unless VO2 max is limited by
      mitochondrial oxidative capacity, as in goats. Cardiovascular structure and
      function in mammals reflects allometric, adaptive and induced variation. Maximal
      heart rate is determined strictly by body size, thus maximal QT/Mb is inevitably
      lower in larger mammals. Adaptive and induced variation elicit hypertrophy of
      muscle, capillaries, and mitochondria, increasing circulatory capacity and VO2
      max. When selection for maximal respiratory function is weak, as in most species
      of mammals, any component(s) of the respiratory system may be underdeveloped,
      relative to other structures in the system, and contribute disproportionately to
      limiting O2 flux. When selection for aerobic capacity is strong, as in
      racehorses, malleable elements of the respiratory system, including the
      cardiovascular structures, may hypertrophy until their capacities for O2
      transport match that of the least malleable structure, the lung. Amplifying
      circulatory function so greatly in a large animal may lead to functional demand
      exceeding structural capacity, resulting in the nearly ubiquitous occurrence of
      exercise-induced pulmonary hemorrhage in racehorses.

PMID- 7801834
TI  - Respiratory gas exchange during exercise.

PMID- 7801835
TI  - Solving the common problem: matching ATP synthesis to ATP demand during exercise.
AB  - Biologists have long known that rates of adenosine triphosphate utilization and
      production need to be extremely closely balanced in all cells at all work rates.
      To put it in molecular rather than molar terms, in human muscle engaged in a 15
      min work protocol, some 3.3 x 10(20) ATP molecules g-1 are used and resynthesized
      at close to 100 times the resting cycling rates before fatigue occurs. However,
      during this interval only a 20-25% decrease in the ATP pool is sustained. Review
      of recent studies as to how such remarkable regulatory precision is achieved
      suggests that in resting muscle, myosin behaves as a latent catalyst for which
      the full catalytic capacity is (a) realized with the arrival of its activator
      signal (Ca2+) and (b) attenuated with reaction products. These proactive
      controls, initiated at the onset of ATP utilization, set the required flux
      through ATP-producing pathways. For any given enzyme step in ATP-producing
      pathways, reaction velocity (upsilon) becomes the independent parameter, whereas
      substrate concentration ([s], the dependent parameter) must be adjusted
      accordingly. Because the dynamic range for muscles (change from resting to
      maximum ATP turnover rates) can exceed 100-fold, in many studies of working
      muscle the percentage change in ATP turnover rate usually greatly exceeds the
      percentage change in substrate concentrations. These kinds of observations are
      not easily explained by current metabolic regulation models, but are consistent
      with pathway enzymes behaving as latent catalysts in resting muscle. In this
      view, the unmasking of such latent catalytic potential is the main explanation
      for how large changes in upsilon can be achieved with modest (sometimes
      immeasurable) changes in [s]. In terms of the basic enzyme velocity equation,
      Vmax = kcat.e0 for pathways of ATP utilization and of ATP synthesis, the dominant
      (coarse level) regulation is achieved through e0 adjustments, whereas fine-tuning
      of flux is achieved by effective kcat adjustment.

PMID- 7801836
TI  - Structural basis of muscle performance.

PMID- 7801837
TI  - [Clinical trial of inhalant recombinant interferon-gamma in patients with
      pulmonary metastasis from renal tumor (preliminary report)].
AB  - Recently, we applied inhalation of recombinant interferon (IFN)-gamma, to 4
      patients with pulmonary metastatic tumor (3 with renal cell carcinoma and 1 with
      renal pelvic tumor). Of the patients with renal cell carcinoma 2 had received
      previous nephrectomy, 1 patient had received embolization alone, 1 subcutaneous
      IFN-gamma in 1, and 1 systematic chemotherapy. All 4 patients inhaled 1 x 10(6)
      JR U-2 x 10(6) JR U recombinant IFN-gamma 3 times per day. Additionally, all
      metastatic renal cell carcinomas received subcutaneous injection of IFN-gamma.
      One patient with renal cell carcinoma achieved a complete response after
      inhalation therapy and 2 patients did not respond (NC: 1, PD: 1). A case of
      metastatic renal pelvic tumor did not respond. Immunohistochemical staining with
      antibody to Ber-MAC3 (stimulated macrophage) of this case revealed positive cells
      within the transitional cell carcinoma. According to these results, inhalation of
      IFN-gamma appears to be applicable as one treatment for pulmonary metastatic
      tumor of renal cell carcinoma.

PMID- 7801838
TI  - [Clinical study on renal pelvic and ureteral tumors].
AB  - Thirty five patients with renal pelvic and ureteral tumors were treated at our
      hospital between 1979 and December 1992. Thirty patients were male and five were
      female. They ranged in age from 44 to 80 years old (average 67.4 years). The most
      frequent symptoms were hematuria that was found in 31 cases (24 gross hematuria
      and 7 microscopic hematuria). Histopathologically, there were 30 transitional
      cell carcinomas (TCC), 1 squamous cell carcinoma (SCC), 2 TCC > SCC and 1
      papillary adenocarcinoma. As to staging, 1 was pTis, 5pTa, 11pT1, 3pT2, 11pT3 and
      4pT4. As to grading, 9 were G1, 16 G2 and 9 G3. The incidence of cancerous vessel
      invasion was noted in 8 of the 29 patients. The 5-year survival rate (Kaplan
      Meier's method) was 44.9% for all of the patients. The 5-year survival rate
      according to staging and according to grading were as follows: 76.7% for low
      stage (pTis, pTa, pT1, pT2), 24.9% for high stage (pT3, pT4), and 83.3% for G1,
      59.9% for G2 and 0% for G3. The 5-year survival rate was 20.8% and 68.7% in the
      patients with and without vessel invasion, respectively. Grade, stage and
      cancerous vessel invasion was suggested to be associated with the prognosis in
      renal pelvic and ureteral tumors.

PMID- 7801839
TI  - [Comparison of treatment results of prostatic cancer between radical
      prostatectomy and radiation therapy].
AB  - Between 1982 and 1990, 55 patients with prostate cancer (clinical stage A2-C)
      underwent pelvic lymphadenectomy at the Public Toyooka Hospital. The patients
      were subsequently treated either by radical prostatectomy (36 cases) or external
      radiation therapy (19 cases). The age of the patients varied from 56 to 85 (Mean
      73.1). The outcome of the 46 patients with negative lymph node (prostatectomy 31,
      radiation 15) were compared. The 10-year disease-specific survival rates were
      100% for the patients treated by prostatectomy and 78% for those treated by
      radiation (P = 0.035). The 5-year progression-free survival rates for the
      prostatectomy group and radiation group were 97% and 56%, respectively (P =
      0.013). Among the radiation groups, patients with well differentiated carcinoma
      showed a lower progression rate as compared to those with moderately or poorly
      differentiated carcinoma (5-year progression-free survival, 81 vs 20%, P =
      0.094). The outcome of the 9 patients with positive lymph node (prostatectomy 5,
      radiation 4) was not satisfactory because of the high progression rates in the
      two groups (5 year progression-free survival, 30% in prostatectomy and 25% in
      radiation group).

PMID- 7801840
TI  - [Treatment of elderly patients with urological cancer].
AB  - The number of elderly patients with urological cancer is increasing, and it is
      becoming very difficult for urologists to decide on an appropriate treatment
      modality for each patient. Physical and socioeconomical problems make it
      impossible for the patients to accept a standard treatment for their disease.
      Between 1987 and 1992, 498 patients with urological cancer were hospitalized in
      our institute. Among them, 51 patients (10%) were 80 years of age or older. The
      average age of these older patients was 83.2 (80-93) years. There were 41 men,
      and 10 women. These older patients included 30 with bladder cancer, 15 with
      prostate cancer, three with renal cancer, and three with renal pelvic and
      ureteral cancer. The incidence of patients aged 80 or older was 18.5% for
      prostate cancer and 15.9% for bladder cancer. Eighty percent of these patients
      had complications such as cardiovascular disease, and fewer patients could be
      adapted treatment because of their physical condition. The median survival period
      was 21.6 months, with only 18 of the patients still living at the time of the
      analysis. Only 11 of the initial 51 patients (22%) still received follow-up
      treatment in the outpatient clinic of our institute, 10 of whom were lost during
      the follow-up. Our observations indicate that we should consider both the medical
      aspects and quality of life when we choose the suitable type of treatment.

PMID- 7801841
TI  - [Changes in the salivary testosterone level in aged].
AB  - Measurement of the level of free testosterone is important in the evaluation of
      testicular function. Because most of the testosterone in the saliva is in the
      free form, measurement of the salivary testosterone level is considered to be
      effective for the evaluation of testicular function. In the present study, a
      commercial kit was employed to measure the salivary testosterone level, and the
      change in the salivary testosterone level with age was investigated. The subjects
      of this study were 76 males, 20-89 years of age, with no endocrinological
      diseases. The concentration of testosterone in the saliva was measured for each
      of the subjects, and for 34 of the subjects the concentrations of total
      testosterone and free testosterone in the serum were also measured at the same
      time. Standard serum was diluted to have a testosterone concentration of 50
      pg/ml, and the results indicated that it was sufficiently possible to measure the
      salivary testosterone. The coefficient of correlation between the salivary
      testosterone concentration and the serum total testosterone concentration was
      0.479 (p < 0.01), while the coefficient of correlation between the salivary
      testosterone concentration and the serum free testosterone concentration was
      0.732 (p < 0.001). These findings thus indicate that the correlation between the
      salivary testosterone concentration and the serum free testosterone concentration
      is better than that between the salivary testosterone concentration and the serum
      total testosterone concentration. It was also demonstrated that the salivary
      testosterone concentration decreased significantly with aging after the fifth
      decade of life. The correlation coefficient for that relationship was -0.606 (p <
      0.001), and the change was similar to that seen in the serum free testosterone
      concentration as a function of aging. The findings suggested that measurement of
      the salivary testosterone concentration with the commercial kit is useful for the
      evaluation of testicular function.

PMID- 7801842
TI  - [A case of malignant pheochromocytoma with high levels of serum neuron-specific
      enolase (NSE) and calcitonin].
AB  - A 71-year-old woman was admitted with the chief complaint of headache, lumbago
      and slight fever. Computerized tomographic (CT) scan demonstrated a large soft
      tissue mass with multiple cystic necrosis in the right adrenal region. The plasma
      norepinephrine concentration was excessive and serum levels of neuron-specific
      enolase (NSE), calcitonin and parathormone were elevated. MIBG scintigraphy
      showed a high uptake in the same region. Under the diagnosis of pheochromocytoma
      without distant metastasis, right adrenalectomy was performed. The tumor was
      removed en bloc with right kidney and a part of the liver because of inflammatory
      adhesion. The histological examination revealed benign pheochromocytoma. After
      the operation, norepinephrine and calcitonin decreased to normal but the levels
      of NSE and PTH remained high. One year after operation, chest X-ray revealed
      multiple lung metastases and after 1.5 years she died of respiratory failure.
      Autopsy revealed multiple lung and bone metastases and a liver metastasis,
      parathyroid glands showed hyperplasia but the thyroid gland showed no abnormal
      change. This clinical course suggests that serum NSE might be a useful tumor
      marker for differentiating malignant pheochromocytoma from benign one, and this
      tumor producing calcitonin caused secondary hyperparathyroidism.

PMID- 7801843
TI  - [A case report of spontaneous renal rupture due to arteriosclerosis].
AB  - A case of spontaneous renal rupture with subcapsular hematoma was reported. The
      patient was a 44-year old man complaining of a sudden left flank pain without any
      recent history of trauma. His abdominal ultrasonography (US), computerized
      tomography (CT) and renal angiography demonstrated left renal rupture with
      subcapsular renal hematoma. Cytological examination of left upper urinary tract
      revealed a suspicion of a neoplasma of renal pelvis and left renal function was
      not recovered. Therefore, left total nephro-uretectomy was performed, and
      histological examination revealed hemorrhage and infarct due to the severe
      arteriosclerosis and intestinal nephritis without malignancy. Sixty-three cases
      of non-traumatic subcapsular renal hematoma reported previously in the Japanese
      literature are reviewed with some statistical analyses.

PMID- 7801844
TI  - [A case of multilocular cystic renal cell carcinoma diagnosed by
      pharmacoangiography].
AB  - A case of multilocular cystic renal cell carcinoma in a 62-year-old man was
      reported. He was admitted with complaint of asymptomatic gross hematuria.
      Abdominal ultrasonography and CT scan revealed multilocular cystic mass at the
      lower pole of the right kidney. Pharmacoangiography demonstrated tumor stain in
      the mass clearly. Radical nephrectomy was performed and histological diagnosis
      was multilocular cystic renal cell carcinoma; cystic type, clear cell subtype, G1
      pT2b pV0 pN0. It is relatively difficult to diagnose multilocular cystic renal
      cell carcinoma but pharmacoangiography was very effective for diagnosis. Renal
      cell carcinoma related multilocular cyst were relatively rare. Eighty-nine cases
      reported in Japanese literatures were discussed statistically.

PMID- 7801845
TI  - [A case of advanced cancer of the renal pelvis effectively treated by continuous
      infusion of 5-fluorouracil].
AB  - We obtained a partial response to a transitional cell carcinoma (TCC) of the
      renal pelvis with multiple metastasis following a 24-hour continuous injection of
      5-FU (5 fluorouracil) over a period of 8 weeks. After treatment we could
      successfully remove the primary lesion. After removal of the primary lesion, the
      patient lived for three months. Because the effects of this treatment, compared
      to those of combination chemotherapy, are mild, it is useful for elderly patients
      with progressive TCC.

PMID- 7801846
TI  - [Primary transitional cell carcinoma in situ of the renal pelvis: a case report].
AB  - A 71-year-old female presented with left back pain at our hospital. She had had
      the same symptom about 1 year previously, but she had been presumed to have
      undergone stone passage because her symptom had disappeared. At this time a
      urogram, either excretory or retrograde, showed narrowing of each caliceal
      infundibulum and dilatation of each calyx in the left kidney, but otherwise
      normal findings. A cytology of left ureteral urine was class V, and cystoscopy
      revealed no abnormality. Under the diagnosis of left renal pelvic tumor she
      underwent nephroureterectomy with resection of a bladder cuff and retroperitoneal
      lymphadenectomy. The resected specimen had no gross tumor throughout the renal
      pelvis and ureter, but histological examination revealed transitional cell
      carcinoma in situ (grade 2) in most of the renal pelvis and infiltration of
      inflammatory cells in the submucosa. The ureter did not have any cancerous
      lesion, and no lymph node metastases was found. Four months postoperatively she
      is thought to have no evidence of disease with negative urinary cytology.

PMID- 7801847
TI  - Successful treatment of hemorrhagic cystitis secondary to cyclophosphamide
      chemotherapy with intravesical instillation of prostaglandin F2 alpha.
AB  - The treatment of cyclophosphamide-induced hemorrhagic cystitis is difficult. We
      report a successful case of severe cyclophosphamide-induced hemorrhagic cystitis
      treated with intravesical instillation of prostaglandin F2 alpha. A 32-year-old
      woman underwent high-dose cyclophosphamide conditioning before the autologous
      bone marrow transplantation. She developed clot retention which required
      continuous irrigation with normal saline. The patient had failed to respond to
      continuous bladder irrigation with saline and intravesical administration of 1%
      alum. Fifty ml of prostaglandin F2 alpha solution (1 mg in 100 ml normal saline)
      was instilled into the bladder, with a dwelling time of 60 minutes, three times a
      day for 5 days. The hematuria cleared completely 3 days after therapy. The only
      adverse effect was bladder spasm which was controlled with oxybutynin chloride.
      The success of this therapy suggests that prostaglandin F2 alpha is a safe and
      useful therapy for hemorrhagic cystitis secondary to cyclophosphamide
      chemotherapy.

PMID- 7801848
TI  - [A case of completely responding stage D2 prostatic cancer with no evidence of
      disease 14 years after diagnosis].
AB  - A 58-year-old male complaining of pollakisuria, miction pain and back pain
      visited us Dec. 26, 1979. Rectal examination revealed the prostate enlarged by 5
      digital width, stony hard and irregular. Transrectal needle biopsy revealed
      moderately differentiated adenocarcinoma of the prostate. Bladder neck invasion,
      pelvic and mediastinal lymph node metastases and multiple bone metastases were
      found. The case was diagnosed with prostatic adenocarcinoma T3N2M1 (OSS, LYM)
      stage D2. Three courses of chemotherapy using ifosfamide applied from Feb. 2,
      1980 showed no marked effect except for partial pain relief. Hormonal treatment
      with diethylstilbestrol diphosphate was started from May 28 and arterial infusion
      chemotherapy using CDDP and 5-FU was performed 2 months later, resulting in size
      reduction of the prostate and pelvic lymph node metastases and disappearance of
      mediastinal lymph node metastases. Needle biopsy of the prostate was negative for
      cancer cells. After 8 months, Tegafur was started, and 12 months later
      radiotherapy was added to the prostate and pelvic lymph nodes. The abnormal
      accumulation in bone scan began to decrease after 14 months and achieved complete
      remission 28 months after the initial therapy. We discontinued the hormonal
      therapy 31 months later because of his complaint of chest discomfort and
      palpitation. At the present time, 14 years after the initial therapy, the
      prostate was 35 x 29 x 19 mm in size on transrectal ultrasonography with
      undetectable serum PSA level and no tumor cells but only mass fibrosis has been
      seen by pathological examinations. We considered this patient to be with no
      evidence of disease.

PMID- 7801849
TI  - [Prune belly syndrome with atresia ani and urethral stricture: a case report].
AB  - A case of prune belly syndrome associated with urethral stricture and atresia ani
      is reported. Cystostomy and colostomy were performed on his birthday. Cutaneous
      vesicostomy, bilateral ureterocystoneoplasty and proctoplasty were performed when
      the patient was one year old, and urethrotomy was performed when he was four
      years old. He was closely followed for six years and six months, and had
      developed without any serious episodes. We collected 128 cases of prune belly
      syndrome from the Japanese literature including this, and made a brief discussion
      of this syndrome with urethral stricture and atresia ani.

PMID- 7801850
TI  - [Scrotal calcification associated with hydrocele testis in a child: a case
      report].
AB  - Scrotal calcification is a rare complication of childhood hydrocele testis.
      Herein, a 12-year-old boy who suffered from left hydrocele testis with
      intrascrotal calcification is reported. The boy had experienced scrotal pain
      about 6 months prior to the first visit to our hospital, and gradually noted
      scrotal swelling. Physical examination revealed left scrotal enlargement with
      transillumination. Sonographic examination revealed a left hydrocele testis, and
      a 1.5 cm discrete focus of calcification was found immediate cranio-lateral to
      the left testis, contour, size and consistency of which were palpated normally.
      In left hydrocelectomy, no appendix epididymidis was found. A smooth, white,
      spherical, firm body connecting to the head of the epididymidis was removed. A
      microscopic examination revealed multiple layers of collagenous tissue with the
      necrotic tissue in the core. We concluded that this case presented with hydrocele
      testis secondary to a growing calcification reacting to the infarction due to the
      repeated torsion of the appendix epididymidis.

PMID- 7801851
TI  - [Endoscopic stone disintegration using the Lithoclast].
AB  - We present our experience with a new and unique device for performing
      intracorporeal lithotripsy known as the Swiss Lithoclast. This simple device uses
      compressed air to activate a solid probe in a manner of a jackhammer. This device
      was used to treat 20 patients with stones in the ureter (11), bladder (5) or a
      Kock pouch (4). The Lithoclast successfully fragmented 90% of the calculi
      independent of the composition and salvaged 2 failed ESWL treatments. At one
      month after the procedure, either alone or in combination of with ESWL, 17 of 20
      patients became free of stones. There were no complications related to use of the
      device. We have found the Swiss Lithoclast to be a safe and effective means of
      performing intracorporeal lithotripsy for urinary calculi.

PMID- 7801852
TI  - [Evaluation of clinical efficacy and safety of cefpodoxime proxetil (CPDX-PR) in
      acute uncomplicated cystitis].
AB  - One hundred and fifty female patients with acute uncomplicated cystitis were
      given 200 mg of CPDX-PR twice daily for 3-7 days to evaluate both its overall
      clinical efficacy and its adverse effects. In 82 cases (Group I) in which it was
      administered for 3 days, the overall clinical efficacy, evaluated by the criteria
      proposed by the Japanese UTI committee, was excellent in 64 cases, moderate in 17
      and poor in one, with the effective rate being 98.8%. In 35 cases (Group II) in
      which it was administered for 4-7 days, the overall clinical efficacy was
      excellent in 18 cases, moderate in 15 and poor in 2, with the effective rate
      being 94.3%. The overall clinical evaluation was not performed in another 33
      cases because they were given CPDX-PR for more than 8 days or 300 mg/day.
      Subjective adverse effects such as hoarseness and lingual inflammation were
      observed in only one of the 150 cases, but they disappeared spontaneously after
      the cessation of administration of CPDX-PR. These findings suggest that CPDX-PR
      is one of the most effective and safe antibiotic in the treatment of acute
      uncomplicated cystitis.

PMID- 7801853
TI  - Platelet aggregability in vivo is attenuated by verapamil but not by metoprolol
      in patients with stable angina pectoris.
AB  - The effects of 1 month of treatment with either verapamil or metoprolol on
      several aspects of platelet function were studied at rest and during physical
      exercise or mental stress in patients with stable angina pectoris participating
      in the Angina Prognosis Study in Stockholm. Platelet aggregability was measured
      by filtragometry ex vivo, which reflects platelet aggregability in vivo and by
      Born aggregometry in vitro. Platelet secretion in vivo was assessed by
      measurements of beta-thromboglobulin in plasma. Verapamil reduced plasma
      norepinephrine levels (from 2.6 +/- 1.0 to 2.2 +/- 1.0 nmol/L; p < 0.01) and
      attenuated platelet aggregability at rest (filtragometry readings were prolonged
      from 219 to 295 seconds; p < 0.05, n = 46). Aggregability in platelet-rich plasma
      was not influenced. Metoprolol did not significantly affect filtragometry
      readings (n = 58) or aggregability in vitro (there was a tendency toward enhanced
      adenosine diphosphate sensitivity; p = 0.08). beta-thromboglobulin levels were
      low (approximately 25 ng/ml) and not influenced by either treatment. Physical
      exercise (bicycle ergometry) increased platelet aggregability in vivo both before
      and after drug treatment. Verapamil also attenuated platelet aggregability after
      exercise, whereas metoprolol had no such effect. Platelet function was not
      seriously altered by mental stress (Stroop's color word test) despite significant
      effects on hemodynamics and plasma catecholamines either before or after
      treatment with either drug. Thus, verapamil attenuates platelet aggregability in
      patients with stable angina pectoris, whereas metoprolol has no such effect.

PMID- 7801854
TI  - Functional cardiac disturbances related to chemotherapy independent of
      anthracycline use in children with neoplastic disease.

PMID- 7801855
TI  - A rare case of coronary artery occlusion diagnosed by echocardiography.

PMID- 7801856
TI  - Effects of left ventricular diastolic dysfunction on exercise capacity three to
      six weeks after acute myocardial infarction in men.
AB  - To examine the effects of left ventricular (LV) diastolic dysfunction on exercise
      capacity, hemodynamic and radionuclide responses were measured at rest and during
      exercise in 50 patients with recent myocardial infarction. The ratio of an
      increase in pulmonary arterial wedge pressure (PAWP) to an increase in LV end
      diastolic volume (EDV) from rest to peak exercise (delta PAWP/delta EDV) was used
      as an index of LV diastolic function, delta PAWP/delta EDV had modest and
      negative correlations with peak oxygen consumption (VO2), cardiac output, and
      stroke volume in all patients. Among patients with peak VO2 > or = 20 ml/min/kg
      (group I, n = 24) and those with peak VO2 < 20 ml/min/kg (group II, n = 26),
      there were no differences between the 2 groups with regard to resting LV ejection
      fraction, EDV, PAWP, cardiac output, and stroke volume. Although there was no
      significant difference in LV ejection fraction at peak exercise, group II had
      significantly reduced EDV, increased PAWP, and decreased cardiac output and
      stroke volume than those in group I. As a result, delta PAWP/delta EDV was
      significantly higher in group II. These results suggest that LV diastolic
      dysfunction has a key role in determining exercise capacity in patients with
      reduced exercise capacity after recent myocardial infarction.

PMID- 7801857
TI  - Prognosis of patients > or = 70 years of age with non-Q-wave acute myocardial
      infarction compared with younger patients with similar infarcts and with patients
      > or = 70 years of age with Q-wave acute myocardial infarction.
AB  - In this study, 70 patients > or = 70 years of age admitted to the coronary care
      unit with non-Q-wave acute myocardial infarction (AMI) were followed
      prospectively for 1 year, and the clinical course in these patients was compared
      with that in 61 patients < 70 years with non-Q-wave AMI and 56 patients > or = 70
      years with Q-wave AMI. Compared with the younger patients with non-Q-wave AMI,
      older patients were more likely to develop atrial fibrillation (23% vs 8%; p <
      0.05) and congestive heart failure (53% vs 30%; p < 0.01), and less likely to
      receive thrombolytic therapy (9% vs 28%; p < 0.01), cardiac catheterization (41%
      vs 72%; p < 0.01), and coronary angioplasty (20% vs 39%; p < 0.05). Hospital
      mortality did not differ significantly between older and younger non-Q-wave AMI
      patients (10% vs 3%), but 1-year mortality was higher in the elderly (36% vs 16%;
      p = 0.02). Elderly patients with Q-wave AMI had more in-hospital complications,
      including death (25% vs 10%; p < 0.05), than elderly patients with non-Q-wave
      AMI. In contrast, postdischarge mortality was higher in elderly patients with non
      Q-wave AMI, so that total mortality at 1 year was similar in the 2 groups.
      Overall, elderly patients with non-Q-wave AMI accounted for 62% of all deaths
      occurring during the first year after discharge (relative risk 2.6 compared with
      other groups; p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7801858
TI  - Intracoronary stenting in the treatment of acute or threatened closure in
      angiographically small coronary arteries (< 3.0 mm) complicating percutaneous
      transluminal coronary angioplasty.
AB  - The effect of the Flex-Stent on immediate and long-term angiographic and clinical
      results for acute and threatened closure was evaluated in 42 consecutive patients
      with coronary arterial segments < 3.0 mm in diameter after percutaneous
      transluminal coronary angioplasty (PTCA). Forty-two consecutive patients were
      treated with Flex-Stent (2.0 or 2.5 mm) for acute or threatened closure
      complicating PTCA. Ten patients (24%) had acute closure and 32 (76%) had
      threatened closure with a residual luminal stenosis of > 50%. Successful stent
      deployment was achieved in 40 patients (95%) with a primary clinical success rate
      of 90% (freedom from myocardial infarction, coronary artery surgery, and death).
      In-hospital complications occurred in 5 patients (some patients fell into more
      than one category): 3 (7.1%) had coronary bypass surgery, 1 (2.4%) had acute
      stent thrombosis, 1 (2.4%) had subacute stent thrombosis, 2 (4.8%) had myocardial
      infarction, and 1 (2.4%) had dextran allergy. There was no hospital death.
      Clinical follow-up was complete at a mean of 14.8 +/- 7.6 months, and recurrence
      of angina was noted in 20 of 38 eligible patients (53%). Angiographic restenosis
      was found in 19 of 29 patients (66%) (76.3% of eligible patients) on follow-up
      angiography (mean 5.9 +/- 4.6 months). Fourteen patients (74%) underwent
      successful repeat PTCA at the stented site, 4 of 38 patients (11%) had bypass
      surgery. Intracoronary stenting in the treatment of acute or threatened closure
      in arteries < 3.0 mm is effective in improving the acute clinical outcome and is
      a viable nonsurgical alternative for this subset of patients.

PMID- 7801859
TI  - Coronary stenting for treatment of ostial stenoses of native coronary arteries or
      aortocoronary saphenous venous grafts.
AB  - This study examines the procedural success, complication, and restenosis rates in
      patients undergoing Palmaz-Schatz stenting of native coronary and saphenous vein
      graft ostial stenoses. All patients undergoing Palmaz-Schatz stent placement of
      ostial lesions (> or = 70% diameter stenosis within 3 mm from the arterial
      ostium) between November 1989 and February 1992 were included in this study.
      Patients were treated with aspirin dipyridamole, low molecular weight dextran,
      and heparin during the procedure and received systemic anticoagulation with
      warfarin for 1 month after the procedure. Angiographic measurements were obtained
      using electronic calipers. Coronary stents were placed in 41 ostial lesions of 41
      patients. The target ostial stenosis was in a saphenous vein graft in 54% and a
      native coronary artery in 46% of lesions. The mean pre- and postprocedural
      minimal luminal diameters were 0.8 +/- 0.7 and 3.3 +/- 0.8 mm, respectively (p <
      0.0001), corresponding to a mean diameter stenosis of 83.5 +/- 10.0% and 1.0 +/-
      4.2%. Two patients had subacute stent thrombosis related to premature
      discontinuation of antithrombotic medications. Two patients died, 1 because of
      stent thrombosis and 1 because of progressive renal failure and sepsis.
      Angiographic follow-up was obtained at a mean of 5.8 +/- 1.8 months in 95% of
      patients with a successful stent procedure. The overall restenosis rate (> 50%
      diameter stenosis at follow-up) was 27.8%. Thus, stenting of ostial native
      coronary and vein graft stenoses can be performed with excellent angiographic and
      procedural success rates. Restenosis rates appear to be lower than expected using
      historical control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7801860
TI  - One-stage coronary angiography and angioplasty.
AB  - The combination of diagnostic angiography and angioplasty as a single procedure
      is becoming common practice in many institutions, but the feasibility and safety
      of this strategy have not been reported. This report describes 2,069 patients who
      underwent coronary angioplasty over a 3-year period at an institution where
      combined angiography and angioplasty is the norm. All patients were prepared
      before angiography for potential immediate angioplasty. In 1,719 patients,
      angioplasty was performed immediately after the diagnostic angiogram, while
      separate procedures were performed in 350 patients. Of those 350 patients, 254
      were referred for angioplasty after diagnostic angiography at other hospitals.
      One thousand one hundred ninety-seven patients were admitted electively for
      treatment of stable angina pectoris, and 872 underwent procedures during
      hospitalization for unstable angina or acute myocardial infarction. One thousand
      nine hundred seven patients (92.2%) had successful angioplasties; in 130 patients
      (6.3%) the lesion could not be dilated, but no complication occurred, and in 32
      patients (1.5%) angioplasty ended with a major complication (0.8% death, 1.0% Q
      wave myocardial infarction, 0.5% emergency coronary artery bypass surgery). There
      was no difference between the combined and staged groups with regard to success,
      major and minor complication rates or in length of hospitalization after
      angioplasty. We conclude that routine combined strategy for angiography and
      angioplasty is feasible, safe, easier for the patient, and more cost-effective
      than 2 separate procedures.

PMID- 7801861
TI  - Enhanced low-density lipoprotein cholesterol reduction and cost-effectiveness by
      low-dose colestipol plus lovastatin combination therapy.
AB  - A total of 96 patients with moderate elevations of low-density lipoprotein (LDL)
      cholesterol were randomly assigned to 4 different double-blind treatment
      regimens: placebo; colestipol 5 g and lovastatin 20 mg/day (C5 + L20); colestipol
      10 g and lovastatin 20 mg/day (C10 + L20); and lovastatin 40 mg/day (L40). During
      12 weeks of therapy, C10 + L20 achieved the greatest reduction in total
      cholesterol (-32%) and LDL cholesterol (-48%) levels from baseline. This
      combination also exhibited significantly greater reductions in LDL cholesterol
      levels than the C5 + L20 and L40 groups (p < 0.01). The differences in total and
      LDL cholesterol reduction between the C5 + L20 and L40 groups were not
      significant. Similar changes and differences between treatments were seen in
      apolipoprotein B levels. Whereas mean total apolipoprotein A-I levels increased
      with all treatments (p < 0.05), lipoprotein particles A-I were significantly
      increased in the C10 + L20 group (p < 0.01) only. Results demonstrate that the
      combination of low-dose lovastatin (20 mg/day) with low-dose colestipol (5 or 10
      g/day) produces LDL cholesterol reductions equal to or greater than higher doses
      of lovastatin (40 mg/day). In addition, low-dose combinations are > 25% more cost
      effective than high-dose monotherapy.

PMID- 7801862
TI  - Safety and efficacy of intravenous diltiazem in atrial fibrillation or atrial
      flutter.
AB  - This study examines the efficacy of various doses of intravenous diltiazem to
      control the ventricular response during atrial fibrillation or atrial flutter.
      Control of the ventricular response of patients with atrial fibrillation and a
      rapid ventricular response can provide patients with relief of symptoms and
      improve hemodynamics. Eighty-four consecutive patients with atrial fibrillation
      or atrial flutter, or both, received an intravenous bolus dose of diltiazem
      followed by a continuous infusion of diltiazem at 5, 10, and 15 mg/hour. The mean
      ventricular response and blood pressure were monitored. Overall, 94% of patients
      (79 of 84) responded to the bolus dose with a > 20% reduction in heart rate from
      baseline, a conversion to sinus rhythm, or a heart rate < 100 beats/min. Seventy
      eight patients received the continuous infusion. After 10 hours of infusion, 47%
      of patients (confidence interval [CI]: 36%, 59%) had maintained response with the
      5 mg/hour infusion, 68% (CI: 57%, 79%) maintained response after the infusion was
      titrated to 10 mg/hour, and 76% (CI: 66%, 85%) after titration from the 5 and 10
      mg/hour infusion to the 15 mg/hour dose. For the 3 diltiazem infusions studied,
      mean (+/- SD) heart rate was reduced from a baseline value of 144 +/- 14
      beats/min to 98 +/- 19, 107 +/- 25, 107 +/- 22, 101 +/- 22, 91 +/- 17, and 88 +/-
      18 beats/min at infusion times 0, 1, 2, 4, 8, and 10 hours, respectively. By the
      end of the infusion, 18% of patients (14 of 78) had conversion to sinus
      rhythm.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7801863
TI  - Usefulness of follow-up electrophysiologic study and event monitoring after
      successful radiofrequency catheter ablation of supraventricular tachycardia.
      Atakr Multicenter Investigators Group.
AB  - We assessed the usefulness of routine follow-up electrophysiologic studies after
      successful catheter ablation for supraventricular tachycardia and the role of
      event monitoring as an alternative modality in 310 patients at 11 centers using
      an investigational catheter ablation system with closed-loop temperature control.
      A routine follow-up electrophysiologic study between 1 and 3 months after
      ablation was required as part of the study protocol, and patients developing
      palpitations after ablation were encouraged to use event monitors. Recurrence of
      the initially targeted arrhythmia developed in 23 patients (7.4%) at a mean of
      1.5 +/- 1.5 months after ablation. However, only 2 of these 23 recurrences were
      discovered by routine follow-up electrophysiologic study in asymptomatic patients
      (both with concealed accessory pathways); in the remaining 21 patients a positive
      follow-up electrophysiologic study was heralded by either recurrent symptoms,
      documented recurrent supraventricular tachycardia, and/or preexcitation on the
      electrocardiogram. Eighteen patients complained of palpitations after ablation
      and received an event monitor, which correctly diagnosed another cause of
      palpitations and ruled out recurrence of the ablated arrhythmia in 8 patients.
      Thus, the combination of clinical follow-up and event monitoring appears to be an
      effective alternative to routine follow-up electrophysiologic studies after
      catheter ablation of supraventricular tachycardia.

PMID- 7801864
TI  - Relation of left ventricular mass and filling to exercise blood pressure and rest
      blood pressure.
AB  - Ninety-two young men with normal blood pressure (BP) or borderline elevated BP
      underwent echocardiography and maximal exercise testing to study whether left
      ventricular (LV) mass and the mitral inflow velocity pattern are more closely
      related to BP measured during dynamic exercise than to pressure measured at rest.
      LV mass was significantly related (p < 0.05) to systolic BP measured at rest and
      at various workloads; however, the variance of LV mass that could be explained by
      exercise pressures, in addition to preexercise pressure, age, body size, resting
      heart rate, and peak oxygen uptake, was not significant. The ratio of the late to
      early mitral inflow velocity was significantly related to systolic BP at rest but
      not to the pressures during exercise, and there was no independent contribution
      of exercise BP to its variance. Thus, systolic BP at various levels of dynamic
      exercise does not contribute independently to the interindividual variance of LV
      mass and mitral inflow pattern in young men with normal or borderline elevated
      BP.

PMID- 7801865
TI  - Transesophageal echocardiographic assessment of reversal of systolic pulmonary
      venous flow in mitral stenosis.
AB  - Transesophageal echocardiography and diagnostic cardiac catheterization were
      performed in 36 patients with symptomatic mitral stenosis to assess the incidence
      and significance of systolic flow reversal in the pulmonary veins. Mitral
      regurgitation was graded by contrast ventriculography, and left atrial pressure
      was directly measured after transseptal puncture. Pulmonary venous flow was
      recorded with transesophageal Doppler imaging from the left upper pulmonary vein.
      Early systolic flow reversal was identified in 11 patients (31%) and began an
      average of 58 +/- 13 ms after QRS onset. This pattern correlated strongly with
      the presence of atrial fibrillation or flutter. Late systolic flow reversal was
      identified in 8 patients (22%), beginning an average of 245 +/- 46 ms after the
      QRS complex. These patients had higher left atrial V-wave pressure (36 +/- 10 vs
      29 +/- 8 mm Hg; p < 0.05) and V-wave peak-X-descent trough (18 +/- 7 vs 11 +/- 5
      mm Hg; p < 0.01) than patients without systolic flow reversal. Neither pattern of
      pulmonary venous flow reversal was related to the severity of angiographic mitral
      regurgitation. Systolic reversal of pulmonary venous flow is not specific for
      angiographically severe mitral regurgitation in patients with mitral stenosis.
      Similar limitations to pulmonary venous flow analysis likely apply to other
      patient groups with elevated left atrial pressure and poor left atrial
      compliance.

PMID- 7801866
TI  - Prevalence, relation to spontaneous closure, and association of muscular
      ventricular septal defects with other cardiac defects.
AB  - Previous studies on muscular ventricular septal defect (VSD) have not taken into
      account the specific defect location in the septum. We retrospectively reviewed
      all patients with a muscular VSD, with and without associated malformations,
      diagnosed over 32 months to determine the prevalence and rate of spontaneous
      closure of single defects in relation to location in the muscular septum. Defects
      were classified into 4 groups: midmuscular, apical, anterior, and posterior. Two
      hundred seven patients were identified, of whom 125 had a single defect. The
      relative prevalence of single muscular VSD was: midmuscular 55 (44%), apical 31
      (25%), anterior 33 (26%), and posterior 6 (5%). Thirty patients had signs of
      spontaneous closure and only 1 underwent surgery. There was no difference in rate
      of closure with respect to anatomic locations. Patients with multiple muscular
      VSD were either referred for surgery in the first year of life or had a course
      similar to patients with a single VSD. Muscular VSD associated with other cardiac
      malformations was more often encountered in patients with conoventricular VSD and
      coarctation of the aorta. The distribution of anatomic groups of muscular VSD in
      association with malformations was similar to the single VSD.

PMID- 7801867
TI  - Effect of size of ventricular septal defect and age on pulmonary hemodynamics at
      sea level.
AB  - In 1,265 patients with isolated ventricular septal defects (Natural History Study
      of congenital heart defects, 1977), older children and adults were classified
      into those with and without pulmonary hypertension. To ascertain why relatively
      distinct pulmonary hypertensive and normotensive groups consisted of older
      children and adults, we reexamined the sea level cardiac catheterization data of
      829 patients according to defect size (using the Gorlin formula) and patient age.
      In patients < 2 years of age, the average pulmonary vascular resistance was not
      significantly elevated and was not dependent on defect size. Pulmonary
      hypertension was due to increased blood flow, except for the 2.7% of patients
      with Eisenmenger-like physiology. For those > 2 years of age, both pulmonary
      arterial pressure and resistance were higher (p < 0.05) in patients with defect
      sizes of > 0.5 cm2/m2 than in those with smaller defects, and the Eisenmenger
      like physiology was more common in older patients (17.4% in patients aged > 10
      years). The group with distinctly higher pressure after 4 years of age reflected
      higher pulmonary vascular resistances in those in whom large defects persisted.
      However, 84% of patients aged > 4 years who underwent cardiac catheterization had
      smaller defects (< 0.5 cm2/m2), accounting for the group observed with low
      pressure.

PMID- 7801869
TI  - Differentiating anomalous left main coronary artery originating from the
      pulmonary artery in infants from myocarditis and dilated cardiomyopathy by
      electrocardiogram.
AB  - Anomalous left main coronary artery (ALMCA) originating from the pulmonary artery
      is an important cause of morbidity from heart failure and mortality in infants.
      Discriminating ALMCA from myocarditis or other forms of dilated cardiomyopathy
      (DC) in infants is critical for proper early management of this treatable
      disease. This study was performed to characterize electrocardiographic (ECG)
      patterns in infants with ALMCA, and to identify features that would allow
      differentiation of these infants from those with myocarditis/DC. Presenting
      electrocardiograms from 28 patients with ALMCA < 2 years of age were analyzed for
      103 variables, and compared with electrocardiograms from 28 aged-matched infants
      with myocarditis/DC using the t test, Fisher's exact test, and discriminant
      analysis using stepwise logistic regression techniques. ECG findings
      characteristic of infants with ALMCA were confirmed, including deep (> or = 3 mm)
      and wide (> or = 30 ms) Q waves and a QR pattern in at least 1 of the following
      leads: I, aVL, V5 to V7. Also, the complete absence of Q waves from leads II,
      III, and aVF in all infants with ALMCA was noted. These and other ECG patterns
      were more common in infants with ALMCA than in those with myocarditis/DC (p <
      0.05), but were also noted in some patients with myocarditis/DC. Stepwise
      logistic regression analysis identified 3 ECG variables that best discriminated
      ALMCA from myocarditis/DC, including Q wave width (w) in lead I, and Q-wave depth
      (d) and ST-segment amplitude (s) in lead aVL.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7801868
TI  - Initial experience with hirudin and streptokinase in acute myocardial infarction:
      results of the Thrombolysis in Myocardial Infarction (TIMI) 6 trial.
AB  - Hirudin is a potent, direct, and highly specific inhibitor of both free and clot
      bound thrombin. Previous reports have shown hirudin to be superior to heparin
      when given with tissue plasminogen activator and aspirin for improving the
      incidence and rate of reperfusion as well as reducing reocclusion of infarct
      related arteries. Patients with acute myocardial infarction were randomized to
      hirudin versus heparin in conjunction with streptokinase (1.5 x 10(6) U) and
      aspirin (325 mg/day). Study drug treatment was a 5-day infusion of either
      heparin, as a 5,000 U bolus, followed by a 1,000 U/hour infusion adjusted to a
      target activated partial thromboplastin time of 65 to 90 seconds (n = 71), or a
      constant infusion of hirudin at 1 of 3 doses (dose 1, n = 55: 0.15 mg/kg bolus +
      0.05 mg/kg/hour infusion; dose 2, n = 31: 0.3 mg/kg bolus + 0.1 mg/kg/hour
      infusion; or dose 3, n = 36: 0.6 mg/kg bolus + 0.2 mg/kg/hour infusion). The
      incidence of major hemorrhage was similar between the heparin group (5.6%) and
      any of the hirudin dose groups (dose 1 = 5.5%, dose 2 = 6.5%, dose 3 = 5.6%). At
      hospital discharge the occurrence of death, nonfatal reinfarction, congestive
      heart failure, or cardiogenic shock was greater in patients receiving the lowest
      dose of hirudin (21.6%) than in those receiving the higher doses of hirudin (dose
      2 = 9.7%, dose 3 = 11.4%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7801870
TI  - Single-stage coronary angiography and angioplasty: a new standard?

PMID- 7801871
TI  - Effects of intravenous ethanol on diameter of epicardial coronary arteries.

PMID- 7801872
TI  - Gender differences in the utilization of cardiac catheterization for the
      diagnosis of chest pain.

PMID- 7801873
TI  - Significance of precordial T-wave inversion in inferior wall acute myocardial
      infarction.

PMID- 7801874
TI  - Relation of thrombotic occlusion of coronary stents to the indication for
      stenting, stent size, and anticoagulation.

PMID- 7801876
TI  - Efficacy and safety of digoxin alone and in combination with low-dose diltiazem
      or betaxolol to control ventricular rate in chronic atrial fibrillation.

PMID- 7801875
TI  - Exercise training and reduction of some coronary risk factors in female cigarette
      smokers.

PMID- 7801877
TI  - Hemodynamic effects of oral propafenone during both sinus rhythm and atrial
      fibrillation.

PMID- 7801878
TI  - The best criterion for discrimination between patients with and without
      paroxysmal atrial fibrillation on signal-averaged electrocardiogram.

PMID- 7801879
TI  - Transposition of the great arteries associated with deletion of chromosome 22q11.

PMID- 7801880
TI  - Maximal exercise tolerance of repatriated prisoners of war.

PMID- 7801881
TI  - Bone marrow histiocytosis and autologous graft failure: possible implications.

PMID- 7801882
TI  - ASCP survey on anatomic pathology examination of the urinary bladder.
AB  - The American Society of Clinical Pathology Quality Management Practice Review
      Committee is sponsoring publication of a series of articles commenting on
      procedures used by pathologists during the examination of various surgical
      specimens. Committee-sponsored survey results serve as the basis for discussion
      and commentary by an expert in the field. Although this information may prove
      useful in forming a practice parameter, it is not the intention of the author or
      the committee to identify this information as a practice parameter. The
      publication of this article does not necessarily represent the opinions or
      endorsement by the ASCP Board of Directors.

PMID- 7801883
TI  - The use of a confirmatory assay to increase the sensitivity and specificity of
      the Chlamydiazyme test.
AB  - The blocking assay was used to reexamine 15,662 patient specimens (2,565 male
      specimens, 13,097 female specimens) that were submitted for Chlamydia detection
      using the Chlamydiazyme EIA assay (Abbott Laboratories, North Chicago, IL).
      Specimens that gave optical density (OD) readings between 1.99 to cutoff and
      between cutoff to 3 times the negative control in the Chlamydiazyme EIA assay
      were analyzed further by the blocking assay during the phase 1 study. In the
      phase 2 study, another 1,120 specimens (473 male specimens and 647 female
      specimens) that had the above mentioned OD range in the Chlamydiazyme assay were
      tested with the blocking assay and the direct fluorescent antibody test using the
      cytospin method. Significant finding from phase 1 study demonstrated that 42.3%
      of the male specimens with optical density between cutoff to three times the
      negative control can be blocked by blocking assay (confirmed positive), whereas
      only 50% of the female specimens with OD range between cutoff to .5 were blocked
      by the blocking assay. In the phase 2 study, similar results were obtained with
      the blocking assay. The direct fluorescent antibody test showed excellent
      correlation with the blocking assay. These data showed that both blocking or
      direct fluorescent antibody tests can be used for confirmation purposes to
      increase the sensitivity and specificity of the assay. However, for specimens
      with OD values below the cutoff to 3 times the negative control, it was necessary
      to reassess the specimens by either of the methods. This was true especially with
      the male specimens.

PMID- 7801885
TI  - Use of rhesus monkey kidney cells for isolation of varicella-zoster virus.
AB  - The authors examined the performance of rhesus monkey kidney cells and human
      diploid fibroblasts (MRC-5 cells) in primary isolation of varicella-zoster virus
      from clinical specimens in a diagnostic virology laboratory. Seventy-two
      varicella-zoster virus isolates were recovered between 1985 and 1993. Twenty
      three isolates (32%) grew only in rhesus monkey kidney cells, whereas four
      isolates (6%) grew only in human diploid fibroblasts (MRC-5)(P = .0001). The time
      to first detection of cytopathic effect was shorter in rhesus monkey kidney cells
      than in fibroblasts. The extent of cytopathic effect was greater in monkey kidney
      cells. In conclusion, the addition of rhesus monkey kidney cells increases the
      yield of varicella-zoster virus and decreases the time required to make a
      definitive diagnosis. The optimal yield of isolates and time to specific
      diagnosis occurs when both monkey kidney cells and human diploid fibroblasts are
      inoculated.

PMID- 7801884
TI  - Histology and Ureaplasma urealyticum culture in 63 cases of first trimester
      abortion.
AB  - The association between chorioamnionitis caused by Ureaplasma urealyticum and
      preterm delivery has been well documented. In contrast, a pathogenic role for
      Ureaplasma has been postulated in early spontaneous abortions, but definitive
      evidence for this association has been lacking. In 42 early spontaneous abortions
      and 21 elective abortions (both first trimester), the chorion was cultured for
      Ureaplasma. Each case was evaluated histologically for four features of
      inflammation and one feature of degeneration. For comparison, 32 selected
      placentas from third trimester preterm deliveries (11 with positive Ureaplasma
      cultures) were examined histologically for umbilical vasculitis and acute
      chorioamnionitis. In abortion specimens, Ureaplasma cultures were positive in 11
      of 42 early spontaneous abortions (26%) versus 0 of 21 elective abortions (EABs).
      None of the five histologic features correlated with positive Ureaplasma cultures
      in early spontaneous abortions. In contrast, in preterm placentas, umbilical
      vasculitis, and acute chorioamnionitis correlated strongly with positive
      Ureaplasma cultures. The authors conclude that in premature delivery, U
      urealyticum chorionic culture positivity is associated with histologic
      chorioamnionitis; and in abortions, Ureaplasma chorionic culture positivity
      correlates with early spontaneous abortions (vs elective abortions), but not with
      histologic inflammation. This suggests that mechanisms of Ureaplasma pathogenesis
      other than acute inflammation should be considered in future studies of early
      spontaneous abortions.

PMID- 7801886
TI  - Improved detection of Cryptococcus neoformans in the BACTEC NR 660 blood culture
      system.
AB  - To determine the impact of continuous agitation versus 24 hours agitation on the
      growth of Cryptococcus neoformans in the BACTEC NR 660 blood culture system, the
      authors compared recovery and detection time for 50 clinical isolates in Peds
      Plus, 26 Plus, and Fungal Medium bottles in paired simulated blood cultures.
      After 144 hours of continuous agitation, the Peds Plus bottle detected 96% of the
      isolates in an average of 82.5 hours, the 26 Plus bottle detected 96% in 79.5
      hours, and the Fungal Medium detected 98% in 81.8 hours. For the bottles that
      were agitated only for the first 24 hours and incubated motionless for 120 hours
      (as recommended by the manufacturer), the Fungal Medium detected 82% of the
      isolates in 100.7 hours. However, the Peds Plus and 26 Plus bottles each detected
      only 38% of the isolates in an average of 112.4 hours and 109.9 hours,
      respectively. These results indicate that continuous agitation of BACTEC blood
      culture bottles for the full incubation time significantly improves (P < or =
      .0001) the detection and recovery of C neoformans.

PMID- 7801887
TI  - Expression of somatostatin receptors in childhood neuroblastoma.
AB  - Somatostatin receptors are expressed on certain neural crest-derived tumors,
      including pancreatic islet cell and carcinoid tumors, medullary thyroid
      carcinomas, pheochromocytomas, and paragangliomas. The authors evaluated the
      expression of high affinity somatostatin receptors in childhood neuroblastoma
      using autoradiography techniques with the somatostatin analogue 125I-octreotide
      or 125I-[Leu8,D-Trp22,Tyr25]-SS-28 as the radioligand. Thirty tumors from 30
      children with neuroblastoma were analyzed. Twenty-three of 30 tumors that were
      tested expressed somatostatin receptors. Correlation of somatostatin receptor
      expression with survival was statistically significant. The survival of those
      patients whose tumors expressed somatostatin receptors was of longer duration
      than that of patients whose tumors did not. This was an independent prognostic
      factor. Somatostatin receptors were expressed more frequently in tumor tissue
      from patients with lower stages of disease and in those with no evidence of N-myc
      amplification. Tumoral somatostatin receptors are expressed in a subgroup of
      patients with childhood neuroblastoma. Survival analysis in this group of
      patients indicates that somatostatin receptor expression is a favorable
      prognostic factor. This finding may have important implications for the therapy
      of children with this malignancy.

PMID- 7801888
TI  - Cutaneous angiosarcoma and atypical vascular lesions of the skin and breast after
      radiation therapy for breast carcinoma.
AB  - Despite the widespread use of radiation therapy to treat breast carcinoma,
      angiosarcomas arising in the field of radiation therapy are rare. The authors
      studied three patients with cutaneous angiosarcoma and four patients with
      atypical vascular lesions (AVL). All had breast conserving surgery, axillary
      lymph node dissection, and radiation therapy for breast carcinoma. Six patients
      received conventional high energy postoperative doses of external beam radiation
      therapy to the breast. Details of radiation therapy were not available for one
      angiosarcoma patient. Angiosarcoma was diagnosed 3.5 years, 3.7 years, and 5.25
      years after radiotherapy. The three angiosarcomas were multifocal or diffuse and
      high grade, with solid cellular foci located mainly in the dermis. In three
      patients AVL presented as discrete skin nodules (2 unifocal and 1 multifocal) and
      in one patient as a breast mass. The four AVL consisted of focal proliferation of
      dilated vascular spaces lined predominantly by a single layer of plump and
      sometimes hyperchromatic endothelial cells. After two angiosarcoma patients
      underwent mastectomy, one died 10 months after diagnosis with recurrent local
      angiosarcoma and the other is alive without angiosarcoma 2 months after
      diagnosis. One angiosarcoma patient died of unrelated causes 2 weeks after
      diagnosis. One AVL patient developed a second cutaneous AVL in the axillary
      region 17 months after excision of an AVL from the same area. None of the AVL
      patients has developed angiosarcoma or recurrent mammary carcinoma. They remain
      well 10 months, 18 months, 7 years and 7 months, and 10 years, respectively,
      after initial local excision. The authors conclude that cutaneous angiosarcoma
      and unusual benign cutaneous vascular lesions can develop within the field of
      radiation therapy for breast cancer. Unlike other radiation therapy-induced
      sarcomas, cutaneous angiosarcoma often occurs within a short time interval after
      radiotherapy. It is important to distinguish AVL from angiosarcoma. Longer follow
      up will be necessary to fully characterize the prognostic importance of atypical
      vascular lesions, but currently there is no evidence that they represent a
      precursor to radiation-induced angiosarcoma.

PMID- 7801889
TI  - Immunological events in regressing genital warts.
AB  - Little is known of the in vivo role of the immune system in controlling human
      papillomavirus infection in the genital tract. The authors have studied 125
      closely monitored patients with genital warts. Of these 125 patients, wart
      regression was seen in 28 patients. This study provides evidence that clearance
      of human papillomavirus from the genital tract is characterized by an active cell
      mediated immune response. Regressing warts (n = 14) contained significantly more
      T lymphocytes (P < .05, Wilcoxon rank sum test) and macrophages (P < .01) than
      did nonregressing controls (n = 14). CD4-positive lymphocytes predominated in
      regression, both within the wart stroma and the surface epithelium, where there
      was a significant change in the ratio of CD4+ to CD8+ cells (P < .01).
      Lymphocytes in regression also showed greater expression of activation markers,
      and the majority were of the "antigen-experienced" phenotype. There was no
      difference in Langerhans cell numbers, although there was significant induction
      of the immune accessory molecules HLA-DR and ICAM1 (P < .05) on keratinocytes,
      and E-selectin and VCAM1 (P < .05) on endothelial cells in regressing warts. The
      changes in regression are consistent with a delayed-type hypersensitivity
      reaction to foreign antigen, and the ability to induce and mount such a response
      may be a critical determinant of effective natural immunity to the genital HPVs.
      Specific targeting of delayed-type hypersensitivity responsiveness may increase
      the efficacy of strategies for immuno-intervention against HPV infection in the
      genital tract.

PMID- 7801890
TI  - Fluorescence in situ hybridization analysis of trisomy 12 in ovarian tumors.
AB  - Conventional cytogenetic studies have suggested that trisomy 12 may be a
      characteristic nonrandom numerical chromosome anomaly in benign ovarian tumors,
      particularly sex cord-stromal tumors. To confirm this finding, and to avoid
      possible culture artifact introduced during cytogenetic analysis, the authors
      performed fluorescence in situ hybridization (FISH) in paraffin-embedded samples
      of select ovarian neoplasms. Forty-four ovarian fibromas and granulosa cell
      tumors and 31 benign and borderline epithelial ovarian tumors were examined for
      the presence of trisomy 12. Trisomy 12 was detected in 40% (8 of 20) of the
      fibromas. No evidence of trisomy 12 was present in 24 granulosa cell tumors,
      although 1 granulosa cell tumor was tetrasomic for chromosome 12. Trisomy 12 was
      found in 27% (3 of 11) of the serous borderline tumors, but was not observed in
      any of the benign epithelial tumors (13 serous and 7 mucinous cystadenomas).
      These results confirm that trisomy 12 occurs in a significant proportion of
      fibromas. However, the incidence of trisomy 12 in granulosa cell tumors is far
      lower than suggested by previous studies. These results, in conjunction with
      those of previous cytogenetic reports, suggest that trisomy 12 is rare in benign
      epithelial ovarian tumors, but occurs fairly commonly as a sole anomaly in
      borderline epithelial tumors. Further investigation is necessary to establish the
      significance of trisomy 12 in the pathogenesis of these tumors.

PMID- 7801891
TI  - Computer-assisted quantitative description of chromatin pattern in soft tissue
      tumors of the adult.
AB  - The chromatin pattern in Feulgen-stained nuclei from soft tissue tumors was
      quantitatively described by means of computer-assisted microscope analysis. The
      morphonuclear parameters described densitometric, run length, and co-occurrence
      matrix features. The present series of cases, which relied upon archival (ie,
      formalin-fixed, paraffin-embedded), tissues, included 19 benign (9 lipomas and 10
      leiomyomas) cases, and 49 malignant (31 primitive non-recurrent, 14 primitive
      locally recurrent, and 4 metastatic) cases. The 31 primitive nonrecurrent cases
      included 12 liposarcomas, 11 leiomyosarcomas, 4 rhabdomyosarcomas, and 4
      malignant fibrohistiocytomas. The results show that the quantitative description
      of chromatin patterns in Feulgen-stained nuclei made it possible to distinguish
      between certain benign and malignant soft tissue tumors. However, this was true
      only when specific histopathologic groups were taken into consideration. Indeed,
      the lipomas were markedly different from the liposarcomas, whereas the leiomyomas
      closely resembled the leiomyosarcomas. The quantitative description of the
      chromatin patterns also made it possible to identify certain clinically
      aggressive soft tissue tumors. In this context, the authors observed that the
      chromatin pattern in the cell nuclei from the group of patients whose tumors had
      recurred less than 10 months after first surgery was significantly more
      heterogeneous and less condensed than in the cell nuclei from patients whose
      tumors had recurred more than 10 months after this surgery. In the same manner,
      the morphonuclear parameters under study made it possible to establish a more
      marked distinction between the primitive and recurrent soft tissue tumors that
      developed a metastasis between 3 and 48 months after the diagnosis, and those
      tumors free of metastasis until 38 months after the diagnosis. The former group
      exhibited cell nuclei with a chromatin pattern markedly more condensed and
      heterogeneous than in the case of the cell nuclei belonging to the latter group.

PMID- 7801892
TI  - A predictive model for fetal lung maturity employing gestational age and test
      results.
AB  - Most laboratory tests for fetal lung maturity (FLM) are optimized to exclude
      false-negative predictions of absence of respiratory distress syndrome (RDS),
      with a reciprocal low predictive value for maturity. The authors employed FLM
      Surfactant/Albumin Ratio (FLM S/A) test results to construct a predictive model
      for FLM that included the obstetric estimates of gestational age. The charts of
      388 newborns were abstracted and reviewed. The clinical outcome was the gold
      standard of the multivariate logistic analysis. Both the obstetric estimates of
      gestational age and the test result were significant predictors of the clinical
      outcome (P values of < .0002 and .001, respectively). The prediction rule for RDS
      as a function of both of these variables allows for adjustment of the test
      cutoffs, so that there is a consistent probability of RDS at the cutoff FLM S/A
      result for different gestational ages. Fetal lung maturity probability reporting
      may facilitate clinical decision-making.

PMID- 7801893
TI  - Euglobulin lysis time in fresh and stored samples.
AB  - Euglobulin lysis time is a global test for the study of fibrinolysis. The aim of
      this study was to evaluate the influence of storage of plasma and euglobulin
      precipitates on euglobulin lysis time, by testing samples stored in different
      conditions. In 20 healthy subjects, euglobulin lysis time was measured by (1)
      euglobulin precipitates prepared within 90 minutes from blood withdrawal
      (reference euglobulin lysis time); (2) euglobulin precipitates obtained from
      platelet-poor plasma stored for 24 hours at either -80 degrees C or at -20
      degrees C; (3) euglobulin precipitates frozen for 24 hours at either -80 degrees
      C or at -20 degrees C; (4) euglobulin precipitates dissolved in Owren's buffer
      and frozen for 24 hours at either -80 degrees C or at -20 degrees C. Euglobulin
      lysis time measured on euglobulin precipitates dissolved in Owren's buffer and
      stored at -20 degrees C and at -80 degrees C, and euglobulin lysis time measured
      on platelet-poor plasma stored at -20 degrees C were significantly longer than
      the reference euglobulin lysis time (at least P < .05). On the contrary, no
      changes were observed in euglobulin lysis time measured on platelet-poor plasma
      stored at -80 degrees C, and on euglobulin precipitates undissolved and stored at
      -20 degrees C and at -80 degrees C versus reference euglobulin lysis time. The
      pattern was similar in samples obtained both before and after venous occlusion.
      These data indicate that the freezing of samples of platelet-poor plasma or
      euglobulin precipitates at -80 degrees C and of euglobulin precipitates at -20
      degrees C makes the simultaneous determination of a large number of samples
      collected at different times the previous day possible.

PMID- 7801894
TI  - An evaluation of 200 consecutive patients with spontaneous or recurrent
      thrombosis for primary hypercoagulable states.
AB  - Two hundred consecutive patients who were referred for evaluation of spontaneous
      or recurrent thrombosis were investigated for possible hypercoagulable states to
      determine the relative frequencies of these conditions in the Australian
      population and to identify features that would indicate which patients should be
      investigated with the expensive battery of tests for hypercoagulable states.
      Thirty-two percent were found to have prolongation of the postvenous occlusion
      euglobulin clot lysis time (PVO-ELT), 32% were found to have elevated levels of
      plasminogen activator inhibitor-1 (PAI) and 66% were found to have reduced
      release of tissue plasminogen activator (tPA). Antiphospholipid antibodies were
      found in 12%. Hereditary antithrombin III deficiency was found in 2%. Hereditary
      deficiency of the naturally-occurring anti-coagulant factors protein C and
      protein S was found in 2%. Age, sex, site of thrombosis (venous or arterial), or
      presence of a family history was not helpful in predicting a group more likely to
      have abnormal investigation results. Reduced fibrinolytic activity and the
      presence of antiphospholipid antibodies are the most common findings in patients
      with thromboembolic disease. Further prospective studies are required to assess
      the natural history and appropriate management of patients with these
      abnormalities.

PMID- 7801895
TI  - Variability of plasma IL-6 and crosslinked fibrin dimers over time in community
      dwelling elderly subjects.
AB  - Because obtaining multiple blood samples from individuals involved in
      epidemiologic studies is difficult, conclusions must be drawn on the basis of one
      or two samples. In this study, the authors attempted to determine the variability
      of two plasma markers over time, namely IL-6 levels and crosslinked fibrin
      degradation products (D-Dimers), in 16 elderly community-dwelling individuals.
      The study group included both men and women and black and white subjects (four in
      each group). Eight blood samples were obtained from each subject over a period of
      36 days. Blood was separated within 1 hour after collection and aliquots of
      plasma were stored at -70 degrees C until all samples were collected. All samples
      from an individual were analyzed at one time. IL-6 and D-Dimers were measured by
      commercially available ELISA kits. The variability in the levels of plasma IL-6
      and D-Dimers was assessed by means of intra-class correlation coefficient (ICC).
      The estimates of the ICCs for one measurement of IL-6 and D-Dimers were .87 and
      .86, respectively. Reliability values of this magnitude indicate excellent
      reproducibility in the measurement. These values indicate that obtaining a single
      sample from a subject is fairly representative of that individual's IL-6 and D
      Dimer levels over an extended period of time.

PMID- 7801896
TI  - The influence of the reference mean prothrombin time on the international
      normalized ratio.
AB  - The International Normalized Ratio (INR) is a mathematical transformation of the
      prothrombin time (PT). The transformation requires a laboratory to compute the
      geometric mean of its own reference population. In this paper, the authors
      examine how the reference mean PT influences the INR accuracy and precision using
      a validated probabilistic model. The variance of the geometric mean of reference
      populations in three laboratory settings was determined. Because the variance of
      an individual laboratory geometric mean is not directly determinable by simple
      parametric equations, its variance is estimated using bootstrap analysis. The
      geometric mean is compared to the computationally simpler arithmetic mean for
      effects on accuracy and precision of the resulting INR. The study shows
      mathematically and empirically that using the arithmetic mean biases INR
      determinations so that patients tend to be over-anticoagulated. However, in the
      laboratory settings examined, the amount of bias was both statistically and
      clinically insignificant. An analysis of the effect on the INR of errors in
      estimating the geometric mean reference PT also is performed. For large biases in
      estimating the reference mean, the INR can be significantly affected and can
      trigger inappropriate clinical actions in patients. The authors demonstrate
      empirically and mathematically that biases in the geometric mean reference PT do
      not affect the INR coefficient of variation. However, they produce significant
      differences in confidence intervals for INR determinations. Laboratories must
      exercise care in determining specific reference means to ensure that biases do
      not occur in geometric mean reference PT determinations. This can be achieved by
      circumspection in the selection of normal subjects for the reference population,
      carefully reviewing the data, and performing the proper calculations on the data.

PMID- 7801897
TI  - Blood volume determination as a function of hematocrit and mass in three
      preservative solutions and saline.
AB  - Accurate blood volume determination is useful both clinically and in research. In
      many instances, however, direct measurement of blood volume is impractical due to
      the risk of bacterial contamination. For this reason, mass is often used to
      estimate volume. The relationship between mass and volume (density) varies with
      different suspension solutions and hematocrits. In this paper, equations are
      derived to calculate volume as a function of hematocrit and mass for pooled red
      cells suspended in four solutions: CPD plasma (whole blood), additive solutions 1
      and 3 (AS-1 and AS-3), and saline. To validate this approach, the actual versus
      predicted blood volumes in 10 individual blood samples suspended in either AS-1
      or saline are compared. The equations predict the volume of blood to within 0.5%
      and 1.0% in samples with low/normal and high hematocrits (15% to 85%,
      respectively). Use of these equations allow for accurate and rapid conversion of
      mass to volume for these blood products.

PMID- 7801899
TI  - Failure to engraft after bone marrow transplantation: bone marrow morphologic
      findings.
AB  - Few studies have explored bone marrow findings in patients with graft failure or
      delayed engraftment after bone marrow transplantation (BMT). The authors
      retrospectively identified 4 patients of 165 transplant recipients who underwent
      bone marrow examination after BMT because peripheral blood counts had not
      recovered to expected levels. All patients were women who were 21- to 49-years
      old (mean 37 years). Three patients underwent autologous BMT; the fourth received
      peripheral stem cell infusion. Transplants were performed for treatment of
      Hodgkin's disease, breast carcinoma, and follicular small cleaved cell lymphoma.
      Three patients received GM-CSF after marrow infusion. The time between transplant
      and biopsy ranged from 19 to 40 days (mean 22 days). White cell counts ranged
      from 0.1 to 0.6 x 10(9)/L, hematocrits from .25 to .41, and platelet counts from
      10 x 10(9)/L to 39 x 10(9)/L. Aspirate smears were markedly hypocellular in all
      cases, and markedly hypocellular, and all contained histiocytes with foamy
      eosinophilic cytoplasm diffusely throughout the biopsy. Acid-fast and Gomori's
      methenamine-silver (GMS) stains were negative. Serous fat atrophy and marrow
      fibrosis were not seen. Delayed engraftment after BMT may be associated with a
      profuse histiocytic proliferation similar to that seen in immunodeficiency, some
      hematologic disorders, and storage diseases.

PMID- 7801898
TI  - Life-long bleeding diathesis: effect of orthotopic liver transplantation.
AB  - Proper regulation of the fibrinolytic system is critical to the prevention of
      both thrombosis and hemorrhage. Patients with inherited or acquired excess
      fibrinolysis may have a bleeding tendency, usually characterized by delayed and
      posttrauma or postoperative bleeding. The liver plays many roles in this
      regulation, including the synthesis of plasminogen, alpha 2-antiplasmin (alpha 2
      AP) and plasminogen activator inhibitor-1 (PAI-1), and the clearance of tissue
      plasminogen activator (t-PA). Inherited deficiencies of alpha 2AP, PAI-1 and
      inherited excess t-PA associated with clinically significant bleeding have been
      reported. The authors describe a patient with a life-long bleeding diathesis who
      demonstrated evidence of excess t-PA. One of two daughters also had a bleeding
      tendency and demonstrated excess t-PA. The patient developed cirrhosis and
      underwent orthotopic liver transplantation. Following transplantation, all
      fibrinolytic parameters returned to normal, and the bleeding diathesis appeared
      to no longer exist. The effect of liver transplantation on this patient's
      fibrinolytic abnormalities and the effect of cirrhosis on this patient's
      laboratory evaluation are discussed.

PMID- 7801900
TI  - Detection of immunophenotypic abnormalities in paraffin-embedded B-lineage non
      Hodgkin's lymphomas.
AB  - The authors analyzed the frequency of immunophenotypic abnormalities in 1,474
      cases of routinely fixed, paraffin-embedded B-lineage non-Hodgkin's lymphomas. B
      lineage was determined by immunoreactivity for CD20 (L26, 92%); CD45RA (4KB5, an
      additional 3%) or immunoglobulin (Ig) light chain restriction (remaining 5%).
      CD45RA was found to be especially helpful on Bouin's-fixed or decalcified tissue
      and Ig staining was most helpful in plasmacytoid lesions. Coexpression of the T
      cell marker CD43 (Leu-22) was the most common immunophenotypic abnormality, seen
      in 60% of mantle cell lymphomas (MCL), 39% of CLL/small lymphocytic lymphomas,
      16% of diffuse large cell lymphomas (DLCL), but only 5% of follicular lymphomas
      (FL). Antibodies to CD45RO (A6 and UCHL1) and CD3 (polyclonal) were useful in
      distinguishing infiltrating T cells from B cells coexpressing CD43. Ig light
      chain restriction was the next commonest immunophenotypic abnormality, which was
      identified in 67% of plasmacytoid diffuse small cell lymphomas, 43% of MCLs, 35%
      of monocytoid B-cell lymphomas and 28% of FLs. Overexpression of bcl-2 oncogenic
      protein was observed in 71% of FLs (n = 96), but not in a control group of
      reactive follicular hyperplasias (n = 34). Combining two criteria increased the
      sensitivity of immunodiagnosis in certain circumstances.

PMID- 7801901
TI  - Expression of the receptor for urokinase-type plasminogen activator in normal and
      neoplastic blood cells and hematopoietic tissue.
AB  - Expression of the receptor for the urokinase type plasminogen activator (uPAR)
      has been studied by flow cytometry and immunohistology in normal blood and bone
      marrow cells, in vitro activated lymphoid cells, and tissue samples from reactive
      lymph nodes (n = 6), thymus (n = 2) and malignant lymphomas (n = 82), or
      leukemias (n = 32). HL-60 myeloid precursor cells and CD34-positive normal stem
      cells also were analyzed. In the normal cells, staining was confined to
      monocytes, macrophages, neutrophils, and myeloid precursors. No labelling was
      seen of normal or activated lymphoid cells. Purified CD34-positive hematopoietic
      progenitors were uPAR negative, but expressed uPAR during differentiation in
      short-term liquid culture stimulated in vitro by recombinant interleukin (IL)-1,
      IL-3, IL-6, granulocyte-macrophage colony stimulating factor (CSF), granulocyte
      CSF, and stem cell factor. Enhanced uPAR expression was also seen in HL-60 cells
      after induction of differentiation with dimethyl sulfoxide or 1 alpha,25
      dihydroxyvitamin D3. In lymphomas and leukemias, the staining pattern was similar
      to that seen in the normal cells with labelling of monocytic and myeloid that
      seen in the normal cells with labelling of monocytic and myeloid malignancies,
      but not of the neoplastic cells in B-cell or T-cell lymphomas or Hodgkin's
      disease. In conclusion, uPAR is a differentiation marker for myeloid and
      monocytic cells, and may act to facilitate migration of these cells in normal and
      pathologic conditions by cell-associated plasminogen activation. Whether
      expression of uPAR in myeloid and monocytic malignancies relates to their growth
      and behavior will be an important topic for investigations in the future.

PMID- 7801902
TI  - Optimization of immunohistochemical detection of P-glycoprotein in chronic
      lymphoid disorders.
AB  - To optimize the immunohistochemical detection of the multidrug resistance (MDR)
      associated P-glycoprotein (P-gp) in chronic lymphoid disorders, the authors
      compared the sensitivity of three different monoclonal antibodies (MoAb) directed
      against P-gp (C219, JSB-1, and MRK 16) by using the APAAP technique on four
      tissue preparations obtained from lymphoid tumors: Cryostat sections, ModAMEX
      processed sections, frozen cytospin preparations, and fresh cytospin
      preparations. Tumor samples were obtained from patients with previously treated
      chronic lymphocytic leukemia (6 cases) or non-Hodgkin's malignant lymphoma (4
      cases). Lymph nodes (n = 9), spleen (n = 3), and blood (n = 5) were analyzed. JSB
      1 MoAb detected P-gp in 4 of 12 cases (33.3%) on either frozen sections or
      ModAMEX processed sections, and in 6 of 17 cases (35.3%) on frozen cytospin
      preparations. The sensitivity of JSB-1 was significantly improved when fresh
      cytospin preparations were used with an incidence of P-gp positive samples as
      high as 70.6% (P < .05). C219 MoAb was unreactive with lymphoid cells whatever
      the technique used, whereas this antibody stained stromal cells. MRK 16 MoAb was
      equally reactive to JSB-1 on fresh cytospin preparations, but unreactive when the
      other preparations were used. The specificity of JSB1 MoAb was confirmed by both
      Western blot analysis and Rhodamine 123 efflux assay. The authors used JSB-1 MoAb
      on fresh cytospin smears prepared from 28 CLL patients. Overall incidence of P-gp
      positive cases was 39.2%. Univariate analysis showed that P-gp expression was
      correlated with prior therapy, refractoriness to treatment, Rai stratification,
      and time of tissue storage after diagnosis. The authors recommend the use of JSB
      1 on fresh cytospin preparations for the immunocytochemical detection of P-gp in
      chronic lymphoid disorders.

PMID- 7801903
TI  - Detection of monoclonal B-cell populations in decalcified, plastic-embedded bone
      marrow biopsies with the polymerase chain reaction.
AB  - Polymerase chain reaction (PCR) has been employed successfully for the detection
      of clonal immunoglobulin gene rearrangements in paraffin-embedded clinical
      samples. The authors examined whether this technique can also be applied to
      fixed, decalcified, and plastic-embedded bone marrow biopsies. DNA extracted from
      66 glycolmethacrylate-embedded trephine biopsy samples was amplified for the
      detection of rearranged VDJ regions of the immunoglobulin heavy chain genes using
      both a single-step and a semi-nested PCR technique. After exclusion of samples
      with inadequate DNA, clonality was confirmed in 16 (67%) of 24 cases with B cell
      malignancy, whereas all 11 non-B cell neoplasms, and 6 of 9 cases with normal
      bone marrow showed evidence of a polyclonal B cell population. Patterns
      indicating oligo- or monoclonality were observed in three plastic-embedded
      samples of normal bone marrow, although control PCR of frozen bone marrow samples
      obtained in parallel showed no evidence of clonality. Repeated PCR of these cases
      revealed inconsistent bands, probably due to the amplification of rare templates
      from polyclonal B cells. Decalcified, plastic-embedded bone marrow biopsies are
      suitable for PCR-based determination of B-cell clonality. To exclude the
      possibility of false-positive results, monitoring of template DNA quality and
      independent control amplifications are mandatory.

PMID- 7801904
TI  - Flow cytometric detection of neoplastic T cells in patients with mycosis
      fungoides based on levels of T-cell receptor expression.
AB  - The authors report the flow cytometric detection of neoplastic T cells in the
      peripheral blood of four out of five (80%) patients with peripheral blood
      involvement with mycosis fungoides (Sezary syndrome) based on the levels of T
      cell receptor expression as measured by CD3 and TCR-alpha beta staining. Antigen
      receptor expression was abnormal in terms of increased density of surface CD3 or
      TCR-alpha beta per cell. Other immunophenotypic abnormalities were present in
      three of these patients. However, in one patient abnormal T-cell receptor
      expression was the only immunophenotypic evidence of neoplasia, although
      morphologically abnormal lymphocytes were present and a T-cell clone was detected
      by polymerase chain reaction (PCR). In another patient, the authors were able to
      detect development of a new, more aggressive neoplastic T-cell population based
      on levels of T-cell receptor expression. Levels of T-cell receptor expression may
      be of diagnostic utility in the evaluation of peripheral blood for the presence
      of neoplastic T-cell populations.

PMID- 7801905
TI  - Mycobacterial spindle cell pseudotumor of the spleen.

PMID- 7801906
TI  - The only good polyp ...

PMID- 7801907
TI  - Safety profile of 5-h oral sodium phosphate regimen for colonoscopy cleansing:
      lack of clinically significant hypocalcemia or hypovolemia.
AB  - OBJECTIVES: Oral sodium phosphate (NaP), a colonic cleansing agent for
      colonoscopy that is superior to standard polyethylene glycol-based lavage
      solutions because of greater patient acceptance, effectiveness, and significantly
      less cost, causes intravascular volume depletion and hyperphosphatemia. To
      determine whether these changes may be near the threshold for inducing clinically
      serious side effects, these parameters were studied in patients receiving two
      doses of NaP over 5 h rather than the conventional 12-h duration. METHODS: 50
      patients (27 outpatients, 23 inpatients) drank 45 ml of NaP at 1700 and 2200 h
      the night before colonoscopy. Patients with renal failure, active heart disease,
      ileus, or gross ascites were excluded. RESULTS: Serial blood tests and
      hemodynamic measurements demonstrated signs of intravascular volume depletion in
      less than 10% of outpatients but up to 40% of inpatients. None of the patients
      complained of postural dizziness or presyncope. All patients became
      hyperphosphatemic (maximum 3.72; normal < 1.30 mmol/L). Measurements of ionized
      calcium were significantly lower compared with baseline values (mean values 1.19
      vs 1.23 mmol/L, respectively). In 44% of patients, these values were below the
      lower limits of normal (1.19 mmol/L) but these changes were minor (lowest value
      1.07 mmol/L) and none of the patients were symptomatic. CONCLUSIONS: This study
      suggests that oral NaP is a safe agent in most patients for colonic cleansing,
      even when given using a 5-h regimen.

PMID- 7801908
TI  - Bleeding from the endoscopically-identified Dieulafoy lesion of the proximal
      small intestine and colon.
AB  - OBJECTIVES: Our goal was to assess the incidence of the endoscopically-identified
      small intestinal and colonic Dieulafoy-like lesions in our GI bleeding population
      and to characterize the clinical and endoscopic features and response to
      endoscopic therapy. METHODS: Patients with GI bleeding from Dieulafoy lesions
      were identified from our Bleeding Team and GI laser data bases from August 1984
      to September 1993. Clinical and endoscopic information contained within the data
      bases and from each patient's medical record were retrospectively reviewed.
      Diagnostic criteria that had been used to endoscopically diagnose a Dieulafoy
      lesion were arterial bleeding or nonbleeding visible vessel stigmata, all without
      ulceration or erosion. RESULTS: Nine patients (three male; six female; median
      age, 70 yr; range, 16-94) were identified from a population of 3059 patients.
      Symptoms included: melena (2); hematochezia (7); and unstable hemodynamics (3).
      The mean hemoglobin was 8.4 +/- 2.2 g/dl. There was no significant nonsteroidal
      antiinflammatory drug or alcohol use. Four patients had small bowel and five
      patients had colonic Dieulafoy's lesions. Specific sites were: distal duodenum
      (3); jejunum (1); cecum (1); hepatic flexure (3); and transverse colon (1). The
      diagnosis was made at initial endoscopy in seven patients, after two endoscopies
      in one patient, and after four in another patient. Active bleeding was
      encountered in seven patients (three small bowel; four colon). Endoscopic therapy
      was successful. Two patients rebled, one from the same site (small bowel) 1 yr
      later. Both were successfully retreated. There were no complications or deaths.
      CONCLUSIONS: The endoscopic Dieulafoy lesion of the small bowel and colon is
      infrequently encountered. The diagnosis is most often made during active
      bleeding. The endoscopic diagnosis requires an aggressive approach, including
      repeated endoscopy. Endoscopic therapy of proximal small intestinal and colonic
      Dieulafoy lesions is safe, effective, and should be performed.

PMID- 7801909
TI  - Well-differentiated hepatocellular carcinoma: clinicopathological features and
      results of hepatic resection.
AB  - OBJECTIVES: To clarify clinicopathological features and surgical results in
      patients with well-differentiated hepatocellular carcinoma (wd-HCC) corresponding
      to Edmondson's cell grading I/I-II. METHODS: The clinicopathological
      characteristics, diagnosis, and results of surgery were studied in 14 wd-HCC
      patients who underwent limited hepatic resection. RESULTS: All patients had liver
      cirrhosis and solitary tumors. The tumor sizes ranged from 10 to 25 mm. Serum
      alpha-fetoprotein levels were normal in 13 patients. The detection rates of
      sonography, computed tomography (CT), angiography, CT during arterial
      portography, 1-wk lipiodol CT, and 3-wk lipiodol CT were 100%, 43%, 36%, 69%,
      57%, and 0%, respectively. High echoic pattern on sonography and disappearance of
      lipiodol 3 wk after injection were characteristic findings. There was no
      operative death. Although seven patients developed intrahepatic tumor recurrence,
      early treatment including ethanol injection therapy and arterial
      embolization/infusion therapy controlled the recurrences in five patients. Eleven
      patients are surviving 25-83 mo after surgery (mean, 44 mo); the remaining three
      died of pneumonia or hepatic insufficiency 44-62 mo after surgery. Eight patients
      received successful direct interruption surgery for concurrent esophagocardia
      varices. Pathological features of wd-HCCs included lack of tumor invasiveness or
      capsule, nuclear crowding, microacinar formation, fat deposition, presence of
      portal tracts, and surrounding adenomatous hyperplasia. CONCLUSION: Wd-HCCs
      present atypical findings in various imagings and histology because of the
      earlier developmental stage of HCCs. Hepatic resection for wd-HCCs provides
      excellent patient survival.

PMID- 7801910
TI  - Hepatitis C infection: a rare cause of fulminant hepatic failure.
AB  - Fulminant hepatic failure is caused by a variety of viruses, toxins, and
      metabolic derangements. The hepatitis C virus (HCV) causes indolent development
      of cirrhosis and has not been associated with fulminant hepatic failure. We
      report the first documented case of fulminant hepatitis C in the United States.
      The patient developed jaundice and stage IV encephalopathy. Initial laboratory
      evaluation did not reveal the etiology. The patient survived without liver
      transplantation. Three wk later he was found to have a positive HCV RNA and anti
      HCV antibody seroconversion. He continued to improve with alpha-interferon
      treatment and has normal liver function and a negative HCV RNA 15 months later.

PMID- 7801911
TI  - Santorinicele as a cause of chronic pancreatic pain.
AB  - The role pancreas divisum plays in recurrent pancreatitis and chronic pancreatic
      pain remains controversial. When pancreatic disease does occur secondary to
      pancreas divisum, the pathogenesis is thought to be stenosis of the accessory
      duct with a resulting increase in ductal pressure. A case is reported in which
      stenosis of the accessory papilla orifice is thought to be responsible for cystic
      dilatation of the terminal portion of the duct of Santorini in a patient with
      pancreas divisum. This resulted in chronic pancreatic pain that resolved after
      sphincterotomy of the accessory papilla.

PMID- 7801912
TI  - Endoscopy and evisceration.

PMID- 7801913
TI  - Pseudointimal biliary epithelial proliferation and Zahn's infarct associated with
      a 6 1/2-month-old transjugular intrahepatic portosystemic shunt.
AB  - The transjugular intrahepatic portosystemic shunt has recently become widely used
      for portal decompression. Shunt stenosis resulting from pseudointimal hyperplasia
      and hepatic encephalopathy are emerging as important midterm complications of the
      procedure. Bile extravasation caused by bile duct transection by the stent wires
      has been suggested as a cause of the pseudo-intimal hyperplasia. The present case
      report describes a 6 1/2-month-old transjugular intrahepatic portosystemic shunt
      in which apparent biliary epithelial proliferation had formed large cyst-like
      spaces within the pseudo-intima at the site of shunt stenosis. We hypothesize
      that secretory products from these biliary epithelial cells may have contributed
      to shunt stenosis by creating expansile cysts or by stimulating pseudointimal
      hyperplasia. In addition, we found a large, recent Zahn's infarct adjacent to the
      stent. Pseudointimal hyperplasia had extended from the stent wires into the
      orifices of contiguous small portal and hepatic vein branches. The resulting
      stenosis of these small veins may have contributed to the Zahn's infarct.

PMID- 7801914
TI  - Bleeding jejunal leiomyoma: a new approach.
AB  - Leiomyomas represent one of the most common benign neoplasms of the small
      intestine. Most of these are asymptomatic and are found incidentally at surgery
      or autopsy; however, leiomyomas may present with prominent signs and symptoms.
      Bleeding is the most common clinical problem and is occasionally life
      threatening. We report the case of a 90-yr-old man who presented with rectal
      bleeding that became massive within hours, necessitating blood transfusion. An
      arteriogram revealed significant hemorrhage from the jejunal branch of the
      superior mesenteric artery (thought to be arteriovenous malformation). Arterial
      embolization was performed, followed after 36 h by therapeutic laparoscopy. The
      area of ischemic bowel was identified, and a 4.5-cm extraluminal jejunal mass was
      resected. Pathological examination confirmed a tissue diagnosis of leiomyoma. Our
      Med-Line search revealed very few cases of jejunal leiomyoma that had presented
      initially as massive rectal bleeding. There were no cases of embolization
      followed by therapeutic laparoscopy.

PMID- 7801915
TI  - Small depressed cancer of the large bowel: report of three cases.
AB  - This report describes three patients in whom colonoscopy detected small depressed
      cancers (without an elevated component) that had invaded the submucosa. They
      represent 0.4% (3/884) of all patients with invasive cancers and 3% (3/101) of
      patients with submucosal cancers in the National Cancer Center Hospital between
      January 1990 and February 1994. This type of cancer may have been overlooked in
      the past because of its small, flat nature. A slight deformity of the lumen, a
      faint color change (slightly reddish), and a loss of a vascular network pattern
      were important colonoscopic findings. Small depressed cancers may follow a
      different pathway to advanced cancer than polypoid cancers, although both
      pathways are included in the adenoma-carcinoma sequence. We should be aware of
      these lesions in our efforts to detect colorectal cancers in the early stage.

PMID- 7801916
TI  - Primary lymphoplasmacytic lymphoma of the liver associated with a serum
      monoclonal peak of IgG kappa.
AB  - We report a case of primary lymphoma of the liver successfully treated by major
      liver resection. The tumor exhibited the immunohistological features of a B-cell
      low-grade lymphoma of the lymphoplasmacytic type. Tumoral plasmacytic cells
      showed cytoplasmic-positive staining for IgG and kappa light chains. In addition,
      we detected a serum monoclonal peak of IgG kappa, a finding that has not been
      reported previously. Clinical, pathological, and immunohistochemical data from
      the literature are reviewed.

PMID- 7801917
TI  - Primary linitis plastica carcinoma of the colon and rectum.
AB  - Primary linitis plastica of the colon or rectum is a rare entity. Only 85 cases
      of this type cancer have been reported in the English medical literature. We
      report two cases, including the oldest known patient presenting uniquely with a
      sigmoid volvulus and another patient presenting with fecal incontinence and
      perianal pain. Linitis plastica of the colon or rectum is characterized by
      presentation in younger patients and is associated with metastatic disease, a
      high mortality, and insidious growth, often making detection difficult. A high
      degree of suspicion must therefore be held; a low threshold for endoscopic and
      echoendoscopic diagnostic intervention also should be maintained. Endoscopic
      ultrasound provides a unique view of its circumferential infiltrating pattern for
      diagnosis and staging, but further experience is necessary to establish whether
      the early use of endoscopic ultrasound favorably impacts mortality.

PMID- 7801918
TI  - Delayed postpolypectomy bleeding.
AB  - Complications of colonoscopic polypectomy include perforation, infection, and
      bleeding. The incidence of bleeding after polypectomy is reported to range from
      one to seven per 1000 polypectomies. This complication usually occurs within a
      few days after the standard procedure using bipolar electrocautery. The longest
      time interval between polypectomy and significant bleeding thus far reported is
      14 days. Most cases of postpolypectomy bleeding are easily recognizable and can
      be effectively treated by colonoscopic electrocauterization. We report here a
      patient who underwent colonoscopic removal of a flat adenomatous polyp at the
      cecum and presented 29 days postprocedure with acute onset of severe bleeding
      from the polypectomy site. A repeat colonoscopy identified this lesion, and
      cauterization successfully stopped this bleeding.

PMID- 7801919
TI  - Prolonged benign pneumoperitoneum after percutaneous endoscopic gastrostomy.

PMID- 7801920
TI  - Endoscopic ultrasound-guided fine needle aspiration of pleural and ascitic fluid.
AB  - Endoscopic ultrasound (EUS) has been established as an important modality for
      staging gastrointestinal malignancies. We have previously described the new
      technique of EUS-guided fine needle aspiration (FNA) in diagnosing submucosal and
      extraluminal tumors and lymph nodes. We now report the novel application of EUS
      and EUS-guided FNA in diagnosing malignant ascites and malignant pleural effusion
      in two patients with gastric carcinoma. In the first patient, CT did not detect
      any effusion or ascites. EUS-guided FNA diagnosed cytologically that both fluids
      were malignant, thereby precluding surgery. The second patient had a small
      pleural effusion on CT that was not detected on the chest x-ray. EUS-guided FNA
      made the cytological diagnosis of recurrent adenocarcinoma in the pleural fluid.
      These two cases demonstrate for the first time that EUS combined with EUS-guided
      FNA can be used for the diagnosis of malignant pleural or ascitic fluid in
      patients with gastrointestinal malignancies and might further extend the staging
      capabilities of EUS.

PMID- 7801922
TI  - Adenocarcinoma arising in an inlet patch of the esophagus.

PMID- 7801921
TI  - Clinical and histopathological variation in hepatocellular carcinoma.
AB  - OBJECTIVES: To assess clinical and histopathological variation in hepatocellular
      carcinoma from different endemic zones and to relate such variation to current
      putative pathogenic mechanisms of carcinogenesis. METHODS: Review of pertinent
      English language articles with emphasis on regional differences as they relate to
      our objectives. RESULTS: Clinical presentation of hepatocellular carcinoma is
      variable in different endemic zones. Such different features may depend on the
      interaction of different etiological initiators and, probably, promoters that can
      lead to different genetic aberrations. Similarly, there also may be
      histopathological variation. However, it is difficult to clearly delineate such
      differences, in part, because of lack of uniformity in reporting interpretation
      of histological data in the literature. And, the ethnic origin of patients is not
      always noted in middle and low endemic zones of hepatocellular carcinoma.
      CONCLUSIONS: Distinction in clinical and histopathological variation in
      hepatocellular carcinoma may benefit from delineating the ethnic origin of
      subjects included in studies and from adoption of clear uniform terminology for
      benign, indeterminate, and malignant lesions.

PMID- 7801923
TI  - Hypogonadal-induced anemia in genetic hemochromatosis: implications for
      phlebotomy therapy.

PMID- 7801924
TI  - Esophageal tuberculosis: a differential diagnostic challenge.
AB  - Esophageal tuberculosis is a rare clinical picture. It is typically secondary to
      tuberculous infection of other organs. There are neither diagnostic signs or
      symptoms nor typical x-ray or laboratory findings. Histology, too, often fails to
      establish a reliable diagnosis, so that esophageal tuberculosis might be mistaken
      for esophageal carcinoma. We report the case of a woman with secondary esophageal
      tuberculosis to illustrate the clinical course and diagnostic problems of this
      condition.

PMID- 7801925
TI  - Estrogen/progesterone treatment of diffuse antral vascular ectasia.
AB  - A case of acute and chronic gastrointestinal bleeding secondary to antral
      vascular ectasia is presented. The pattern of antral vascular ectasia was the
      diffuse form. After attempted treatment with endoscopic laser photocoagulation
      proved ineffective, the bleeding was treated with an estrogen/progesterone
      combination. The bleeding ceased with this medical therapy. The lesion of antral
      vascular ectasia persisted, however, despite the cessation of bleeding. Attempted
      maintenance therapy, consisting of reduction in frequency of
      estrogen/progesterone therapy to every third day, resulted in resumption of
      bleeding, requiring reinstitution of daily therapy for control.

PMID- 7801926
TI  - A case of extrahepatic biliary cystadenocarcinoma arising in the hepatoduodenal
      ligament.

PMID- 7801927
TI  - Albendazole: new hope for treatment of microsporidiosis in AIDS.

PMID- 7801928
TI  - Helicobacter pylori brews ferment in MALT lymphoma.

PMID- 7801929
TI  - Cryptosporidium emerges from the watery closet.

PMID- 7801930
TI  - Giant duodenal ulcer and nonsteroidal anti-inflammatory drug use.

PMID- 7801931
TI  - Re: "Three-dimensional demonstration and endoscopic treatment of
      pancreaticoperitoneal fistula".

PMID- 7801932
TI  - Epidemiology of celiac disease.

PMID- 7801933
TI  - Limitations of ultrasound for measuring gallbladder bile emptying and refilling.

PMID- 7801934
TI  - Long-term HIV infection with Crohn's disease.

PMID- 7801935
TI  - Crohn's disease, HIV, and AIDS.

PMID- 7801936
TI  - Modified short-term triple therapy--ranitidine, clarithromycin, and metronidazole
      -for cure of Helicobacter pylori infection.

PMID- 7801938
TI  - Acute mesenteric ischemia after colonoscopy.

PMID- 7801937
TI  - Scruples not rubles: is therapeutic ERCP being utilized appropriately?

PMID- 7801939
TI  - Transient detection of antinuclear and anti-smooth muscle antibodies in hepatitis
      A virus infection.

PMID- 7801940
TI  - The expression of H-ras p21 product in esophageal cancer from Hong Kong Chinese.

PMID- 7801941
TI  - Esophagocutaneous fistula from cancer esophagus: management by esophageal
      endoprosthesis.

PMID- 7801942
TI  - Liver transplantation for hepatitis B: where do we go from here?

PMID- 7801943
TI  - Diminutive colonic polyps: histopathology, spatial distribution, concomitant
      significant lesions, and treatment complications.
AB  - OBJECTIVES: Our objectives in this study were to determine diminutive colonic
      polyp histology, distribution, frequency of significant synchronous neoplastic
      lesions, and treatment complications. METHODS: We evaluated consecutive
      colonoscopic examinations in which one or more diminutive polyps were detected
      over a 36-month period; these examinations had been entered into an endoscopy
      database at the time of colonoscopy. RESULTS: A total of 1964 diminutive polyps
      were found and removed in 753 colonoscopies; 1525 were removed by hot biopsy, 436
      were removed by cold biopsy, and three were removed by snare. Of the diminutive
      polyps, 40.7% were adenomatous, 37.2% were hyperplastic, 17.9% were mucosal tags
      or lymphoid aggregates, and 4.3% were mixed; 0.26% contained atypia, and none
      were cancerous. In the right colon and transverse colon, diminutive polyps were
      more likely to be neoplastic (p < 0.0001), but in the left colon they were more
      likely to be nonneoplastic (p < 0.0001). The prevalence of synchronous neoplastic
      lesions was 21.5%. No perforations were seen; however, significant hemorrhages
      occurred in six cases in which hot biopsy was used. The risk of a significant
      hemorrhage from hot biopsy of diminutive polyps was 0.39%. The risk of hot biopsy
      induced hemorrhage was significantly higher in the right colon than in the
      transverse colon and left colon (p < 0.05). The risk in the cecum was 1.33%; in
      the ascending colon it was 1.03%, and for the remainder of the colon it was
      0.24%. CONCLUSIONS: Most diminutive polyps proximal to the left colon are
      neoplastic. The decision to use the hot biopsy or cold biopsy technique to
      eradicate diminutive polyps should take into account the location of the polyp
      because of the significantly increased risk of hemorrhage with hot biopsies in
      the right colon.

PMID- 7801944
TI  - Clinical course and survival after liver transplantation for hepatitis B virus
      infection complicated by hepatocellular carcinoma.
AB  - OBJECTIVES AND METHODS: The outcome after liver transplantation for HBsAg
      positive liver disease complicated by hepatocellular carcinoma is not clearly
      defined, and in the present study we analyzed the clinical course in 39 patients
      transplanted for hepatitis B virus (HBV)-related liver disease (group 1) compared
      with 16 patients with chronic HBV and hepatocellular carcinoma (group 2) and 52
      patients with primary hepatocellular carcinoma seronegative for HBsAg (group 3).
      RESULTS: Despite similar pretransplant viral serology, HBV recurred more often in
      patients with tumor (group 2) than in nontumor cases (group 1), with 1-yr
      actuarial cumulative reinfection rates of 85.4% versus 65.0%, respectively (p <
      0.05). In group 2 cases, we observed a more aggressive pattern of HBV-related
      graft injury with a higher frequency of graft loss (56.3% vs. 12.8%, p < 0.001).
      Long-term outcome was worse in the group 2 cases, with 5-yr actuarial survival
      rates of 16.7% compared with 73.2% and 28.2% for groups 1 and 3, respectively. In
      group 2, recurrence of HBV in the graft, rather than tumor recurrence, was the
      principal cause of the high mortality observed (56.2% vs. 12.5%), which, in some
      cases, may have been potentiated by adjuvant chemotherapy. CONCLUSION: The poor
      outcome of patients transplanted for HBsAg-positive cirrhosis and hepatocellular
      carcinoma is due to HBV reinfection of the graft, rather than tumor recurrence.
      Antiviral agents in association with hepatitis B immunoglobulin would be the most
      promising approach to improving survival in this patient population.

PMID- 7801945
TI  - The preoperative evaluation of patients considered for laparoscopic antireflux
      surgery.
AB  - Few studies address the proper extent of the preoperative testing in patients
      referred for consideration of antireflux surgery. Our aim was to perform a
      thorough gastroesophageal evaluation and determine its influence on the
      therapeutic decisions of such patients. We evaluated 107 consecutive patients in
      a combined GI/Surgery clinic for severe or refractory gastroesophageal reflux.
      The patients had an EGD, esophageal manometry, and 24-h ambulatory esophageal pH
      monitoring. Only patients with gastric symptoms had gastric testing. Nineteen
      patients were excluded, 12 refused further evaluation and seven were felt to be
      unfit for antireflux surgery because of medical or psychological reasons. Eighty
      eight patients completed the required studies. Fifty-four patients (61%) had
      typical reflux symptoms and erosive esophagitis on EGD. All these patients had an
      abnormal pH study. Five of the 34 patients without esophagitis had a normal pH
      study and did not have surgery. Ten patients had poor peristalsis by esophageal
      manometry prompting a subtotal fundoplication. One patient had severe delayed
      gastric emptying, requiring pyloroplasty in addition to the fundoplication.
      Eighty of 83 patients had good or excellent surgical results. EGD and esophageal
      manometry are indispensable in the preoperative evaluation. Manometry may
      identify abnormalities altering surgical decisions in roughly 10% of patients.
      Routine ambulatory esophageal pH monitoring is of marginal benefit, except in
      patients without esophagitis or in those patients where the diagnosis is in
      doubt. Clinically significant gastric abnormalities are rare, and routine testing
      of gastric function is not indicated.

PMID- 7801947
TI  - Physicians' emotional reactions to patients: recognizing and managing
      countertransference.
AB  - Traditionally, physicians have been socialized to repress emotional responses to
      patients in an effort to maintain clinical objectivity. In this article we call
      into question that assumption, maintaining that rather than being hindrances such
      natural responses can be facilitators to the development of stronger physician
      patient relationships. We focus on the concept of countertransference, defined
      here broadly as incompletely recognized emotional reactions a physician has
      toward a patient or his/her circumstances. In this article we differentiate
      between internally-focused and externally-focused countertransference. Internally
      focused countertransference refers to unrecognized reactions that reflect the
      unique psychological state of the physician, whereas externally-focused
      countertransference focuses on the reactions that primarily derive from the
      behaviors or other characteristics of the specific patient or circumstances. We
      conclude by presenting a 3-step strategy for recognizing and managing
      countertransference responses to patients.

PMID- 7801948
TI  - Long-term results of heater probe thermocoagulation for patients with massive
      peptic ulcer bleeding: a prospective observation.
AB  - OBJECTIVE: The long-term rebleeding rate of a bleeding ulcer after endoscopic
      hemostasis is, so far, not clear. The goal of this study is to present the
      natural history of bleeding ulcers after heater probe thermocoagulation. METHODS:
      Between September 1986 and June 1991, we used heater probe to treat 202 patients
      with active bleeding or nonbleeding visible vessels at the ulcer craters. We were
      able to follow 159 patients for 2-7 yr (mean +/- SD: 54.5 +/- 19.9 months).
      Patients with active bleeding or nonbleeding visible vessels who did not receive
      endoscopic hemostasis or surgery in our previous studies served as controls.
      RESULTS: The energy applied to each patient in the heater probe group was 886 +/-
      844 J (mean +/- SD). The ultimate hemostatic rate in the heater probe group was
      91.2% (145/159). In the period of long-term follow-up, there were 32 episodes of
      rebleeding in 24 patients (16.6%). Most rebleeding episodes (22/32) subsided
      spontaneously. Only one rebleeding patient died before a surgical attempt. The
      rebleeding rate was less than that of the controls (43/87, p < 0.0001).
      CONCLUSION: Heater probe thermocoagulation is very effective in arrest of peptic
      ulcer bleeding. In the long-term follow-up, heater probe thermocoagulation can
      decrease rebleeding rate in most patients with peptic ulcer hemorrhage.

PMID- 7801946
TI  - Risk of extraesophageal malignancy in patients with adenocarcinoma arising in
      Barrett's esophagus.
AB  - OBJECTIVES: It has been suggested that the presence of Barrett's mucosa is a
      marker for potential malignancy in other organs. Our objective was to study
      subjects with adenocarcinoma of the esophagus arising in Barrett's epithelium.
      METHODS: We reviewed the medical records of patients with esophageal
      adenocarcinoma, with esophageal squamous cell carcinoma, and with no esophageal
      pathology and recorded the occurrence of extraesophageal malignancies and the
      heavy use of tobacco and alcohol. RESULTS: The prevalence of extraesophageal
      malignancies was not higher in patients with esophageal adenocarcinoma (15%) than
      in patients in either control group (14% each). Patients with either type of
      cancer of the esophagus had higher rates of tobacco and alcohol use than normal
      controls (tobacco: p = 0.02 and p < 0.01 for adenocarcinoma and squamous cell
      carcinoma, respectively, vs. normal controls; alcohol: p < 0.01 for each
      esophageal malignancy vs. normal controls). The rate of tobacco and alcohol use
      was higher in patients with esophageal squamous cell carcinoma than in those with
      adenocarcinoma, but only the difference in alcohol consumption was statistically
      significant (p < 0.01). CONCLUSION: Patients with adenocarcinoma of the esophagus
      are not at higher risk for development of extraesophageal malignancy. This
      observation applies to both those with and without underlying Barrett's
      epithelium. Alcohol and tobacco use appear to be related to the malignant
      transformation of esophageal epithelium.

PMID- 7801949
TI  - Effects of intravenous nitroglycerin and nitroglycerin and metoclopramide on
      intravariceal pressure: a double blind, randomized study.
AB  - OBJECTIVE: Effective and safe reduction of variceal pressure by pharmacological
      means. METHODS: Twenty patients with portal hypertension and large esophageal
      varices. Ten patients received i.v. nitroglycerin (300 micrograms-bolus) and an
      equal number received a combination of i.v. nitroglycerin (150 micrograms) and
      metoclopramide (20-mg bolus). Continuous measurement of variceal pressure and
      systemic hemodynamics was carried out. RESULTS: Compared with the baseline, the
      variceal pressure was reduced at 10 min after injection of 300 micrograms
      nitroglycerin (22.3 +/- 7.9 vs. 17.3 +/- 7 mm Hg, p, not significant); the
      percentage reduction was 23.5 +/- 15.8%. With the combination of low dose (150
      micrograms) nitroglycerin and metoclopramide, variceal pressure significantly
      decreased from 23.1 +/- 4.7 to 15.9 +/- 5.9 mm Hg (p < 0.01) (a reduction of 29.5
      +/- 24.1%). There was no significant alteration in the heart rate or mean
      arterial pressure with either regimen. CONCLUSIONS: Our results suggest that a
      combination of i.v. metoclopramide and low-dose nitroglycerin reduces variceal
      pressure more effectively than high-dose nitroglycerin used alone. This
      combination should be further evaluated in the control of acute variceal
      bleeding.

PMID- 7801950
TI  - A 1-h topical therapy for the treatment of Helicobacter pylori infection.
AB  - OBJECTIVE: A novel topical therapeutic methodology for the treatment of
      Helicobacter pylori infection was developed and studied in 25 patients with H.
      pylori to evaluate safety and efficacy. METHODS: The patients had been given
      lansoprazole (30 mg, hs) orally and pronase (18,000 tyrosine units, b.i.d.) for
      the 2 days before topical therapy. One hundred milliliters of solution with 80 ml
      of 7% sodium bicarbonate and 20 ml of contrast medium meglumine sodium
      amidotrizoate containing bismuth subnitrate (1 g), amoxicillin (2 g),
      metronidazole (1 g), and pronase (36,000 tyrosine units) were instilled into the
      stomach through a nasally introduced 16-Fr intestinal tube with a balloon at its
      radiopaque tip, which was inflated with approximately 25 ml of air and lodged
      postbulbarly at the superior duodenal angle under fluoroscopy, thus preventing
      leakage of the solution distally into the jejunum. The solution was kept in the
      stomach for 1 h, and the patient's position was changed every 15 min from the
      sitting to the supine, prone, and right lateral position to expose the entire
      gastric mucosa. The solution was suctioned at the end of the procedure. RESULTS:
      H. pylori infection was successfully cured in 24 (96%) patients, confirmed 4 wk
      after the therapeutic procedure by negative smear, culture, and histology of the
      antral and corpus biopsy specimens. No side effects were observed except for
      loose stools in one case. CONCLUSION: This 1-h topical therapy is a safe,
      effective, and well tolerated procedure for the treatment of H. pylori infection.
      With further improvements and modifications of the method itself, as well as of
      the drug regimens, this method may become a highly efficient modality for anti-H.
      pylori therapy.

PMID- 7801951
TI  - Helicobacter pylori infection does not increase gastric antrum mucosal cell
      proliferation.
AB  - OBJECTIVES: Gastric carcinoma is the world's second most common cancer. Recent
      studies suggest an association between Helicobacter pylori and gastric carcinoma.
      The aim of this study was to address the effects of H. pylori infection on
      gastric antrum mucosal cell proliferation. METHODS: Forty patients undergoing
      upper endoscopy for standard indications were included in the study. A rapid
      urease test was used to determine the presence of H. pylori. Epithelial cell
      proliferation was determined by immunohistochemical techniques utilizing
      monoclonal antibody to bromodeoxyuridine. RESULTS: There were no significant
      differences in the number of labeled cells and in the proliferation fraction (p >
      0.1) when patients with H. pylori were compared with those without, and when
      those over the age of 50 were compared to those under 50. The presence of ulcers
      similarly had no effect (p > 0.1). CONCLUSION: Helicobacter pylori infection does
      not increase gastric antrum mucosal cell proliferation.

PMID- 7801952
TI  - Acute pancreatitis in long-distance runners.

PMID- 7801953
TI  - Biliary tract calculi in primary sclerosing cholangitis.
AB  - By conventional criteria the diagnosis of primary sclerosing cholangitis (PSC) is
      excluded if biliary tract calculi are present. OBJECTIVE: To compare patients
      with sclerosing cholangitis with and without calculi. METHODS: Retrospective
      review between 8/91 and 9/93 identified 63 patients with sclerosing cholangitis
      alone (Group A) and 22 patients with sclerosing cholangitis and biliary tract
      calculi (Group B). The mean follow-up was 13.6 months. Clinical features reviewed
      were age, sex, associated inflammatory disease (IBD), and clinical presentation.
      Cholangiographic features compared were site and extent of disease. Endoscopic
      stone extraction was reviewed for success and complications. RESULTS: Both groups
      had the following features in common: 1) mean age (45.9 vs 46.3 yr), 2)
      prevalence of IBD (68.3 vs 72.7%), 3) extent of bile duct strictures
      (intrahepatic: 28.5% vs 27.2%; extrahepatic: 12.7% vs 13.6%; both: 58.7% vs
      54.5%). There were proportionately more women in Group B (45.5% vs 33.3%).
      Symptomatic presentation (pain, pruritus, jaundice, and cholangitis) was seen
      more often in Group B: 86.4% compared with Group A: 39.7% (specifically
      cholangitis was seen in 22.7% vs 4.7%). Among Group B, calculi developed
      subsequent (mean 40.2 months) after the diagnosis of sclerosing cholangitis in
      77.3% of patients. The distribution of calculi was cholelithiasis: 7 (31.8%);
      choledocholithiasis: 9 (40.9%); and both: 6 (27.2%). Of the patients with
      choledocholithiasis alone, 78% had undergone previous cholecystectomy. Endoscopic
      stone extraction was successful in 13 (86.6%) of the patients with
      choledocholithiasis. Complications included mild pancreatitis in one patient and
      bleeding from sphincterotomy site in another patient which responded to
      sclerotherapy. In follow-up, only one patient had recurrent calculi and underwent
      successful stone extraction. CONCLUSION: We suggest that biliary tract calculi
      are a part of the spectrum of otherwise typical PSC and therefore their presence
      should not necessarily exclude the diagnosis.

PMID- 7801954
TI  - Mycobacteria in the intestine of Japanese patients with inflammatory bowel
      disease.
AB  - OBJECTIVES: It is still controversial whether or not a mycobacterial infection
      may be a cause of Crohn's disease. Mycobacterium paratuberculosis may be very
      difficult to detect using routine culture techniques. To clarify this, we
      detected mycobacterial DNA in patients with inflammatory bowel disease. METHODS:
      IS900 sequences highly specific to M. paratuberculosis and the groEL gene
      encoding a conserved mycobacterial antigen were studied in colonic mucosa using
      polymerase chain reaction (PCR). PCR products were analyzed by Southern blot
      hybridization. RESULTS: IS900 sequences were detected in all (100%) of 10
      patients with Crohn's disease, in 11 (61.1%) of 18 patients with ulcerative
      colitis, and in 14 (87.5%) of 16 control patients with noninflammatory bowel
      disease. All IS900 positive samples had groEL PCR products. CONCLUSIONS: Our
      results, on the basis of the prevalence, do not support the hypothesis that M.
      paratuberculosis is involved in the pathogenesis of Crohn's disease.

PMID- 7801955
TI  - Laser-induced fluorescence microscopy of normal colon and dysplasia in colonic
      adenomas: implications for spectroscopic diagnosis.
AB  - OBJECTIVES: To determine what structures fluoresce and to what extent in normal
      colon and colonic adenomas to fully exploit laser-induced fluorescence
      spectroscopy as a tool for the diagnosis of dysplasia at endoscopy. METHODS:
      Unstained frozen sections of normal colon and colonic adenomas were studied by
      fluorescence microscopy under 351-364-nm argon ion laser excitation. Tissue
      fluorescence was observed and compared to morphology in serial sections stained
      with hematoxylin and eosin (H&E), Movat pentachrome, mucicarmine, and oil red O.
      RESULTS: In normal colon, fluorescence correlated morphologically with connective
      tissue fibers (principally collagen) in all layers of the bowel wall and with
      cytoplasmic granules within eosinophils present between the crypts in the lamina
      propria of the mucosa. Fluorescence of absorptive cells in normal crypts was very
      faint, and Goblet cells did not fluoresce. However, marked fluorescence was
      observed in the cytoplasms of dysplastic epithelial cells in the crypts of
      colonic adenomas. Fewer fluorescent connective tissue fibers were present in the
      lamina propria of colonic adenomas resulting in decreased fluorescence intensity
      as compared to that of normal colon. Fluorescent eosinophil granules were present
      in larger numbers in adenomas as compared with normal colon. CONCLUSION: Laser
      induced fluorescence in normal colon and colonic adenomas correlates with
      morphology. Previous reported differences in laser-induced fluorescence emission
      spectra of normal colon and colonic adenomas obtained in vitro and in vivo may be
      due to differences in the cytoplasmic fluorescence between the dysplastic
      epithelium in colonic adenomas and normal colonic epithelium. Laser-induced
      fluorescence spectroscopy may be useful in studying other forms of epithelial
      dysplasia such as that which occurs in ulcerative colitis.

PMID- 7801956
TI  - Gastrointestinal symptoms in bulimia nervosa: effects of treatment.
AB  - OBJECTIVES: The aim of this study was to characterize the frequency and severity
      of gastrointestinal symptoms in bulimic patients and to determine their response
      to treatment of the eating disorder. METHODS: Forty-three consecutive bulimic
      patients admitted to the inpatient Eating Disorders Unit of the Psychiatry
      Service were asked to fill out a gastrointestinal symptoms questionnaire, an
      Eating Disorders Inventory, and a Zung Depression Inventory on admission and
      discharge. Thirty-two age- and sex-matched healthy volunteers completed the same
      questionnaire. RESULTS: In bulimic patients, the most commonly reported
      gastrointestinal symptoms were bloating (74.4%), flatulence (74.4%), constipation
      (62.8%), decreased appetite (51.2%), abdominal pain (48.8%), borborygmi (48.8%),
      and nausea (46.5%). The average symptom score (sum of severity ratings) on the
      gastrointestinal symptoms questionnaire decreased from 20.6 +/- 10.8 (mean +/-
      SD) on admission to 13.46 +/- 10.5 (t(27) = 3.31, p < 0.01) on discharge but
      remained significantly higher than that of the control group (4.4 +/- 6.2, t(43)
      = 4.02, p < 0.001). However, the severity of reported gastrointestinal symptoms
      was correlated with the severity of depression (r = 0.43, p < 0.05), and when the
      possible mediating effects of depression on gastrointestinal symptoms were
      controlled statistically (analysis of covariance), the effects of treatment on
      gastrointestinal symptoms were not statistically significant. CONCLUSION:
      Gastrointestinal symptoms in bulimics are common, multiple, and often severe and
      they improve with treatment. However, the most important determinant of
      gastrointestinal symptoms appears to be depression.

PMID- 7801957
TI  - The gastrointestinal manifestations of Sjogren's syndrome.
AB  - Sjogren's syndrome (SS) is an autoimmune exocrinopathy that primarily affects the
      salivary glands but can also involve almost any other part of the gut. The most
      distressing manifestation of SS is xerostomia secondary to destruction of the
      salivary glands. The lack of saliva also leads to difficulty with chewing and
      initial swallowing and an increased frequency of dental caries. Another major
      problem is dysphagia due to the lack of saliva as well as esophageal dysmotility
      and/or esophageal webs. Chronic atrophic gastritis probably accounts for the
      epigastric pain, nausea, and other dyspeptic symptoms seen in SS. Sjogren's
      syndrome is also one of the most frequent extrahepatic diseases associated with
      primary biliary cirrhosis, suggesting that this entity may be a secondary form of
      SS. The degree to which SS affects the small and large bowel is unclear, whereas
      pancreatic involvement appears to lead to only subclinical exocrine
      insufficiency.

PMID- 7801958
TI  - A novel stable isotope breath test: 13C-labeled glycosyl ureides used as
      noninvasive markers of intestinal transit time.
AB  - OBJECTIVES: Breath tests are widely used for diagnosis and control of treatment
      efficacy. There is a need for breath test substrates that reflect intestinal
      transit times under various conditions. METHODS: We synthesized a new class of
      breath test substrates, 13C-labeled glycosyl ureides, which are specific markers
      for the action of colonic microbial flora. We then investigated their usefulness
      as markers of intestinal transit time. RESULTS: Bolus ingestion of 1 g lactose or
      cellobiose 13C-ureide resulted in bacterial cleavage of the N-glycosyl bond and
      subsequent urea hydrolysis. 13CO2 appeared in breath and was determined by gas
      isotope-ratio-mass spectrometry. Label first appeared after 5-6 h, peak excretion
      occurred between 8-14 h, and the signal returned to baseline after 18-24 h.
      Metoclopramide (10 mg) administered 1 h before the substrate advanced the onset
      of the signal by 2.4 +/- 1.95 h (mean +/- SD; n = 7; p < 0.05) and the time of
      peak response by 0.8 +/- 1.44 h. Loperamide (16 mg) broadened the peak and
      delayed the time of breath signal onset by 1.0 +/- 2.78 h and peak excretion by
      4.0 +/- 3.7 h (p < 0.05). CONCLUSIONS: The glycosyl ureide breath test reflected
      intestinal transit time and rapid changes in gastrointestinal motility. This test
      should be useful in the diagnosis of a variety of gastrointestinal motility
      disorders and in the development of drugs that affect gastrointestinal motility.

PMID- 7801959
TI  - Prospective evaluation of patients with bowel wall thickening.
AB  - OBJECTIVE: Thickening of the gastrointestinal bowel wall is commonly identified
      by abdominal computed tomographic (CT) imaging. The objective of this study was
      to prospectively determine the prevalence of substantial pathological
      abnormalities in patients with bowel wall thickening by computed tomography.
      METHODS: Consecutive patients with bowel wall (gastric, duodenal, or colonic)
      thickening prospectively identified by CT underwent endoscopy of the portion of
      the bowel that was identified as abnormal. RESULTS: Over an 18-month period, 50
      patients with bowel wall thickening underwent directed endoscopic examination.
      Fifteen patients of the cohort were HIV-positive. The likelihood of detecting an
      abnormality by endoscopy in the entire population was 67%. Furthermore, for
      patients with endoscopic abnormalities, 42% had a specific histological diagnosis
      made by biopsy taken during the endoscopy. Clinical parameters did not predict
      abnormal endoscopic findings for patients with an abnormal computed tomographic
      exam. Although the rate of endoscopic abnormalities did not significantly differ
      between HIV-positive and HIV-negative patients, specific histological findings
      were more common among the former patients. CONCLUSIONS: In patients with bowel
      wall thickening identified by CT, endoscopy demonstrates abnormalities in the
      majority of cases. Endoscopy is useful in this patient population because it
      yields accurate identification of abnormalities and also permits direct biopsy.
      Among patients with bowel wall thickening identified by CT, in whom a specific
      diagnosis is not evident, endoscopy of the relevant portion of the bowel should
      be strongly considered.

PMID- 7801960
TI  - Diagnosis of hypertensive end-stage renal disease: effect of patient's race.
AB  - The authors conducted a simulation study to examine whether the race of a patient
      with end-stage renal disease (ESRD) influences the diagnosis of underlying kidney
      disease made by the nephrologist. The hypothesis was that ESRD may be more
      readily ascribed to hypertension in blacks than in whites. Nephrologists
      practicing in Maryland during 1991 were sent written case histories based on the
      presentation of seven patients with ESRD. For each case history, the patient's
      race was randomly assigned to be "black" or "white." The nephrologist's diagnosis
      of underlying renal disease was recorded as "hypertensive" or "other." Analysis
      of 197 case histories from 58 physicians (81% of those eligible) was performed
      using logistic regression. The distribution of underlying causes of ESRD in the
      case histories was similar to national statistics: hypertensive ESRD, 34%;
      diabetic ESRD, 30%; glomerulonephritis, 11%; other, 16%; unknown, 10%. Case
      histories that identified the patient's race as black were more likely (odds
      ratio = 1.97; 95% confidence interval 1.05-3.68) to result in a diagnosis of
      hypertensive ESRD than case histories in which the patient's race was said to be
      white, after adjustment for case history. Analyses that accounted for the
      physicians' individual tendencies to diagnose hypertensive ESRD yielded similar
      results. These findings suggest that black ESRD patients may be more likely to be
      labeled as having hypertensive kidney disease than white ESRD patients with
      similar clinical histories. Using race as a criterion to establish diagnoses of
      kidney disease may obscure the interpretation of incidence statistics, affect the
      management of individual patients, and hinder epidemiologic studies of risk
      factors for kidney failure. Definition of clear diagnostic criteria for the
      underlying cause of kidney failure is highly desirable.

PMID- 7801961
TI  - Modeling incidence rate ratio and rate difference: additivity or multiplicativity
      of human immunodeficiency virus parenteral and sexual transmission among
      intravenous drug users. Northern Italy Seronegative Drug Addicts Study.
AB  - The analysis concerns data from the Northern Italian Seronegative Drug Addicts
      Study, a multicenter longitudinal study about the incidence of human
      immunodeficiency virus infection in intravenous drug users from Milan and other
      areas of northern Italy between 1987 and 1991. Different measures of parenteral
      and heterosexual exposure effects were estimated by fitting multiplicative models
      for rate ratio and additive models for both rate ratio and rate difference into a
      Poisson regression model for grouped cohort data. In areas of high human
      immunodeficiency virus prevalence among intravenous drug users, the adjusted rate
      ratio under a multiplicative structure was 6.2 (95% likelihood-based confidence
      interval (LCI) 2.9-14.4) for parenteral and 2.9 (95% LCI 1.3-6.1) for sexual
      transmission. Under the additive model, the rate ratio was 7.8 (95% LCI 3.4-20.2)
      for parenteral and 9.2 (95% LCI 2.2-29.7) for sexual transmission, and the rate
      difference per 100 person-years was 9.8 (95% LCI 5.3-15.6) for parenteral and
      10.5 (95% LCI 1.8-24.2) for sexual transmission (controlled for each other).
      Because of the small sample size, a clear discrimination between models could not
      be reached. However, in spite of the greater risk associated with parenteral
      transmission under a multiplicative model, the additive model suggests that the
      relative impact of measures aimed at inducing condom use is similar to that which
      would be obtained by measures aimed at stopping syringe sharing.

PMID- 7801962
TI  - Parent monitoring and the incidence of drug sampling in urban elementary school
      children.
AB  - An epidemiologic study of urban-dwelling children aged 8-10 years in Baltimore,
      Maryland, was undertaken to test the hypothesis that close monitoring and
      supervision by parents might signal a reduced risk of drug use in the elementary
      school years. Drug use, monitoring by parents, peer drug use, and other suspected
      risk factors for early drug use were first assessed in 1989, identifying 947
      children with no prior history of drug use. One year later, 4.2 percent of these
      children were found to have started using alcohol, tobacco, or other drugs on
      their own for the first time during the follow-up observation interval. Risk of
      starting drug use was higher for children with lower levels of parent monitoring
      (relative risk = 4.39, 95% confidence interval 1.48-13.0). In addition, for
      children with declining levels of parent monitoring, there was an increased risk
      of starting to use drugs on their own.

PMID- 7801963
TI  - Performance on the digit symbol substitution test and 5-year mortality in the
      Western Collaborative Group Study.
AB  - The relation between performance on the digit symbol substitution test and
      subsequent 5-year mortality was examined in 1,118 male participants in the
      Western Collaborative Group Study (mean age at time of examination = 70.6 years).
      Cox regression analyses revealed that the unadjusted relative risk from all-cause
      mortality was 1.79 (95% confidence interval 1.45-2.21) for subjects who scored 10
      points (1 standard deviation) lower on the digit symbol substitution test. The
      relative risk remained significant at 1.44 (95% confidence interval 1.12-1.86)
      after adjustment for age, education, baseline serum cholesterol, and systolic
      blood pressure levels and for the prevalence of cancer,
      cardiovascular/cerebrovascular disease, and ever smoking. Tree-structured
      survival analysis revealed the presence of a subgroup of subjects (n = 130) with
      low digit symbol substitution performance (mean = 26.3) who experienced a
      mortality rate of 34.9 deaths per 1,000 person-years. This mortality rate was not
      significantly different from that encountered by another subgroup of subjects
      with a history of cancer (n = 128; 45.7 deaths per 1,000 person-years). If age
      related slowing of information processing is a marker for aging of the central
      nervous system, then people with lower digit symbol scores may be "older"
      physiologically than similarly aged persons with higher digit symbol scores.
      Aging of the central nervous system might be expected to reduce adaptive capacity
      in a general way, thereby increasing susceptibility to death from a variety of
      causes.

PMID- 7801964
TI  - The age selection of mortality from tuberculosis in successive decades. 1939.

PMID- 7801965
TI  - Cognitive functioning and the incidence of limitations in activities of daily
      living in an elderly community sample.
AB  - Although it is well-known that cognitive impairment in the elderly is usually
      accompanied by limitations in activities of daily living (ADL), it is not known
      whether cognitive impairment predicts the onset of new ADL limitations. The
      purpose of this analysis was to determine whether poor scores on a brief measure
      of cognitive functioning at baseline (1982) would predict the onset of persistent
      limitations in ADL during the subsequent 3 years, in a probability sample of
      community-dwelling elderly persons living in New Haven, Connecticut, who were
      initially free of ADL limitations (n = 1,856). Cognitive functioning was assessed
      with Pfeiffer's Short Portable Mental Status Questionnaire. Persistent incident
      ADL limitations were defined as the onset of one or more ADL limitations after
      1982, with no subsequent reports of zero ADL limitations. Compared with persons
      who scored zero to one errors on the Short Portable Mental Status Questionnaire
      at baseline, persistent, incident ADL limitations occurred more frequently in
      persons who scored four or more errors (odds ratio for males = 2.72, 95%
      confidence interval 1.36-5.43; odds ratio for females = 2.60, 95% confidence
      interval 1.52-4.44) after adjustment for the confounding effects of housing type,
      age, race, history of chronic health conditions, and incident health conditions.
      These results suggest that knowledge of scores on brief cognitive function tests
      can be used to forecast service needs and to develop intervention programs to
      prepare for the possible onset of ADL limitations.

PMID- 7801966
TI  - Effect of risk factors and changes in risk factors on coronary mortality in three
      cohorts of middle-aged people in eastern Finland.
AB  - The association of smoking, serum cholesterol, and blood pressure with coronary
      mortality and the contribution of changes in these risk factors to the decline in
      coronary mortality was assessed in three cohorts of middle-aged population
      examined in 1972, 1977, and 1982 in Eastern Finland. A total of 10,758 men and
      11,112 women were included in this study. The follow-up time of each subject was
      8 years. Age-adjusted coronary mortality decreased from 54 per 10,000 person
      years in the 1972 cohort to 30 per 10,000 person-years in the 1982 cohort among
      men and from eight per 10,000 person-years to four per 10,000 person-years among
      women in the 1972 and 1982 cohorts, respectively. Concomitantly with the decrease
      in coronary mortality, there was a marked decrease in cardiovascular risk
      factors. Among men, the age- and geographic area-adjusted hazard rate ratio of
      coronary mortality between 1972 and 1982 cohorts was 0.52 (95% confidence
      interval (CI) 0.38-0.72). After further adjustment for smoking, serum
      cholesterol, and blood pressure, the hazard rate ratio was 0.74 (95% CI 0.54
      1.02). Among women, the corresponding hazard rate ratios were 0.49 (95% CI 0.21
      1.12) and 0.73 (95% CI 0.30-1.71), respectively. Therefore, it can be estimated
      that in both sexes nearly half of the decrease in coronary mortality hazard was
      associated with the changes in risk factors. The fall in serum cholesterol level
      among men and the decrease in blood pressure among women contributed most of the
      decrease in coronary mortality hazard.

PMID- 7801967
TI  - Case-control study of caffeinated beverages and preterm delivery.
AB  - Although many women reduce their caffeine consumption once they known they are
      pregnant, 70-80% of pregnant women still consume caffeine. To evaluate the
      relation between caffeine consumption and preterm delivery, a case-control study
      was conducted to identify all preterm (< 37 weeks gestation) infants born to
      women in selected North Carolina counties from September 1988 through April 1991.
      Randomly selected full-term, normal-weight livebirths (matched by race and
      hospital) served as controls. The study population consisted of 408 cases and 490
      controls. Telephone interviews with participants assessed the consumption of
      caffeinated coffee, tea, cola soft drinks, and noncola caffeinated soft drinks,
      with caffeine consumption measured by the number of daily servings of each
      beverage and the total milligrams of caffeine. Third-trimester caffeine
      consumption from all beverages combined showed a nonsignificant inverse
      association with preterm delivery. Both first- and second-trimester consumption
      of 1-150 mg/day were associated with a modestly increased risk of preterm
      delivery, while no association was found at higher consumption levels. Overall,
      these results do not support an association between caffeinated beverage
      consumption and preterm delivery, as is true in most previous studies.

PMID- 7801968
TI  - Tree-based risk factor analysis of preterm delivery and small-for-gestational-age
      birth.
AB  - Using data collected at the Yale-New Haven Hospital, New Haven, Connecticut, in
      1980-1982, the authors conducted a tree-based statistical analysis using preterm
      delivery and small for gestational age as outcomes and the following variables as
      putative risk factors: maternal age, marital status, ethnicity, education,
      current employment, smoking, alcohol use, caffeine consumption, marijuana use,
      hormones/diethylstilbestrol used by the mother, gravidity, parity, and passive
      smoking. The authors' analyses indicate that ethnicity is a leading factor
      contributing to both outcomes: Black women are more likely to have preterm
      deliveries as well as to deliver small-for-gestational age infants. The tree
      based procedure leads to generally consistent results with more traditional
      secondary analyses of the same data set, but also provides a more fully
      integrated picture of the important relation. The full utility of these
      procedures for hypothesis generation remains to be explored.

PMID- 7801969
TI  - Population-based study of the contribution of weather to hip fracture
      seasonality.
AB  - Previous studies have demonstrated seasonal increases in hip fracture incidence,
      but none have directly assessed the influence of inclement weather on this
      seasonality. In this study, the daily occurrence of hip fracture among women aged
      45 years and older in Rochester, Minnesota, from 1952 through 1989 was
      ascertained using the resources of the Rochester Epidemiology Project and
      compared with the occurrence of inclement weather as recorded in hourly readings
      by the National Weather Service in Rochester for the same time period. Among the
      women aged 45-74 years, the risk of hip fracture was increased on days with snow
      (relative risk (RR) = 1.41, 95% confidence interval (CI) 1.10-1.81) or freezing
      rain (RR = 1.82, 95% CI 1.27-2.62). In this group, the elevated risk of hip
      fracture in winter, compared with summer (RR = 1.44, 95% CI 1.0-2.09), was
      reduced after controlling for weather (RR = 1.16, 95% CI 0.81-1.65). Among women
      aged 75 years and older, ice and snow were not strongly related to fracture
      occurrence. The winter-related increase in risk (RR = 1.16, 95% CI 0.96-1.40) was
      essentially unchanged after controlling for weather and was similar to the
      weather-adjusted seasonality of hip fracture occurrence in younger women. These
      data suggest that there are factors other than weather that may be linked to the
      seasonal pattern in hip fracture occurrence and that operate at all ages.

PMID- 7801970
TI  - Re: "Dietary fat intake and carotid artery wall thickness: the Atherosclerosis
      Risk in Communities (ARIC) Study".

PMID- 7801971
TI  - Re: "Vegetables, fruit, and colon cancer in the Iowa Women's Health Study".

PMID- 7801972
TI  - Enterprise liability for medical malpractice and health care quality improvement.

PMID- 7801973
TI  - Quality assessment of ethics in health care: the accountability revolution.

PMID- 7801974
TI  - Bad "bad baby" bills.

PMID- 7801975
TI  - Patient accountability and quality of care: lessons from medical consumerism and
      the patients' rights, women's health and disability rights movements.

PMID- 7801976
TI  - Value purchasing in Medicare law: precursor to health reform.

PMID- 7801977
TI  - Redefining the terms of health insurance to accommodate varying consumer risk
      preferences.

PMID- 7801978
TI  - Universality, quality & economics: finding a balance in Ontario and British
      Columbia.

PMID- 7801979
TI  - Enterprise medical liability and the choice of the responsible enterprise.

PMID- 7801980
TI  - Outcomes assessment in health care reform: promise and limitations.

PMID- 7801981
TI  - Quality improvement in community-based, long-term care: theory and reality.

PMID- 7801982
TI  - Redefining quality by reassigning responsibility.

PMID- 7801983
TI  - Haemophilus influenzae disease declines by 95% in young children.

PMID- 7801984
TI  - Calcium intakes too low, says federal panel.

PMID- 7801985
TI  - Growth hormone as an adjunct to parenteral nutrition.

PMID- 7801986
TI  - Agents for treating human immunodeficiency virus infection.
AB  - The replicative cycle of the human immunodeficiency virus (HIV) is reviewed, and
      currently used and investigational agents directed against the virus are
      discussed. The first step in the replication of HIV is selective binding of the
      envelope glycoprotein to CD4 receptors located on T lymphocytes. The virion is
      then uncoated within the cytoplasm, yielding viral genomic RNA. Reverse
      transcriptase uses the viral RNA as a template to form single-stranded DNA, which
      is duplicated to form proviral DNA through the activity of ribonuclease H. Host
      RNA polymerases transcribe the integrated proviral DNA into messenger RNA, and
      there is subsequent translation to viral proteins. After translation, further
      modification of precursor polyproteins is necessary to produce functional
      peptides. The assembled virus then buds from the cell surface and invades other
      cells. Targets of drug intervention in the replicative cycle include (1) binding
      and entry, (2) reverse transcriptase, (3) transcription and translation, and (4)
      viral maturation and budding. Inhibitors of binding and entry include recombinant
      soluble CD4, immunoadhesins, peptide T, and hypericin. Nucleoside reverse
      transcriptase inhibitors include zidovudine, didanosine, zalcitabine, and
      stavudine. Foscarnet, tetrahydroimidazobenzo-diazepinthione compounds, and
      nevirapine are some nonnucleoside reverse-transcriptase inhibitors. Inhibitors of
      transcription and translation include antagonists of the tat gene and GLQ223.
      Castanospermine, N-butyldeoxynojirimycin, and protease inhibitors interfere with
      viral maturation and budding. Drug combinations that have been or are being
      investigated include zidovudine plus interferon alfa, zidovudine plus
      zalcitabine, and zidovudine plus didanosine. Four agents currently have approved
      labeling for use against HIV infection: zidovudine, didanosine, zalcitabine, and
      stavudine. Monotherapy with zidovudine remains the treatment of first choice.
      Although progress has been made in developing drug therapies for HIV infection,
      more selective and more potent drugs are urgently needed. The best approach at
      present is to optimize the use of available agents, continue to investigate new
      therapies, and educate the public about prevention.

PMID- 7801987
TI  - Factors associated with preventable adverse drug reactions.
AB  - Factors associated with preventable adverse drug reactions (ADRs) in a community
      hospital patient population were studied. The following data were collected by
      concurrent review of all ADRs reported from July 1992 through January 1993:
      patient demographics, ADR variables, length of stay, and preventability of ADR.
      These data were analyzed to determine factors associated with preventable ADRs.
      Of the 203 ADRs reported, 38 (19%) were identified as preventable. The only
      significant difference found between preventable and nonpreventable ADRs was in
      severity (preventable ADRs were more severe). Length of stay (LOS) for patients
      who experienced ADRs was longer than the national average for patients in the
      same diagnosis-related group. Most of the preventable ADRs involved (1) a
      documented allergy to medication ordered or to similar medications, (2)
      anticoagulants or thrombolytics, (3) that required serum drug concentration
      monitoring (in the absence of pharmacokinetics service involvement), and (4)
      renally eliminated drugs for which dosage adjustments were not made in patients
      with impaired renal function. Strategies for minimizing ADRs were developed based
      on these factors. An ADR reporting program helped in identifying preventable
      ADRs, determining factors associated with preventable ADRs, and developing
      strategies for preventing ADRs in a community hospital patient population.

PMID- 7801988
TI  - Stability of piperacillin sodium-tazobactam sodium and ranitidine hydrochloride
      in 0.9% sodium chloride injection during simulated Y-site administration.
AB  - The stability of piperacillin sodium plus tazobactam sodium and ranitidine
      hydrochloride in 0.9% sodium chloride injection during simulated Y-site
      administration was studied. Triplicate test solutions of piperacillin 40 mg/mL
      plus tazobactam 5 mg/mL (as the sodium salts) or piperacillin 80 mg/mL plus
      tazobactam 10 mg/mL (as the sodium salts) were mixed 1:1 with ranitidine 0.5 and
      2.0 mg/mL (as the hydrochloride salt). The solutions were stored at 23 degrees C,
      and samples were removed at zero, one, two, and four hours for measurement of
      drug concentration by stability-indicating high-performance liquid
      chromatography. At the time of sampling and before any dilution, each sample was
      visually inspected for color and precipitation, and pH was determined. At all
      sampling times, the concentrations of piperacillin, tazobactam, and ranitidine
      were > 90% of initial concentrations. There were no substantial changes in pH or
      color. Tazobactam 5 mg/mL (as the sodium salt) and ranitidine 0.5 and 2 mg/mL (as
      the hydrochloride salt) in 0.9% sodium chloride injection were stable for up to
      four hours during simulated Y-site administration. Piperacillin 80 mg/mL plus
      tazobactam 10 mg/mL (as the sodium salts) and ranitidine 0.5 and 2 mg/mL (as the
      hydrochloride salt) were stable for up to four hours during simulated Y-site
      administration.

PMID- 7801989
TI  - Linking a policy on nonformulary drugs to the FDA's therapeutic-potential
      classification system.

PMID- 7801990
TI  - Therapeutic interchange of fluoxetine and sertraline: experience in the clinical
      setting.

PMID- 7801991
TI  - Criteria for use of fluvoxamine maleate in adult inpatients and outpatients.

PMID- 7801992
TI  - Prescribing errors for patients about to be discharged from a university teaching
      hospital.

PMID- 7801993
TI  - Visual compatibility of fluconazole with drugs given by continuous infusion.

PMID- 7801994
TI  - Compatibility of cyclizine lactate and haloperidol lactate.

PMID- 7801995
TI  - How to get started with computerized literature searches.

PMID- 7801996
TI  - Epidemiology of congenital hydrocephalus in Utah, 1940-1979: report of an
      iatrogenically related "epidemic".
AB  - As part of an epidemiological study of congenital hydrocephalus in Utah, we
      focused on the effect of ascertainment sources and temporal variability to
      further delineate the causes of this relatively common, handicapping birth
      defect. The incidence and distribution of 934 reported cases diagnosed prior to
      age 6 months, and born to Utah residents from 1940 to 1979, were analyzed. Data
      were ascertained by examination of multiple sources, e.g., 982,066 birth, 11,161
      fetal death, and 248,208 death certificates, and selected hospital and clinic
      records. Of the 934 reported cases, 700 met our selection criteria for congenital
      hydrocephalus, which results in a crude incidence of 0.70 per 1,000 live and
      stillbirths. Seventy-one cases (10.1%) had additional, multiple congenital
      anomalies. The male/female sex ratios of the 619 cases of isolated congenital
      hydrocephalus (occurring as a single entity or in the absence of other reported
      or known birth defects) and those with multiple congenital anomalies (71 cases)
      were virtually identical, being 1.45 and 1.48, respectively. A significant 85%
      increase in the rate of reported cases was observed for the period 1966 to 1970.
      However, examination of patients' records from 1966 to 1975 in the hospital
      responsible for almost all of this increase suggests that this was an
      iatrogenically related "epidemic" caused by several factors: the introduction and
      possible misinterpretation of pneumoencephalograms (PEG) in the diagnosis of
      hydrocephalus (PEG was replaced by CAT scanning in the early 1970s),
      inappropriate diagnosis, and incorrect recording of age at time of diagnosis.

PMID- 7801998
TI  - Mental retardation and Ullrich-Turner syndrome in cases with 45,X/46X,+mar:
      additional support for the loss of the X-inactivation center hypothesis.
AB  - Four cases having mosaicism for a small marker or ring [45,X/46,X,+mar or
      45,X/46,X,+r] chromosome were ascertained following cytogenetic studies requested
      because of minor anomalies (cases 1, 3, and 4) and/or short stature (cases 2 and
      4). While all 4 cases had traits typical of Ullrich-Turner syndrome (UTS), cases
      1, 3, and 4 had manifestations not usually present in UTS, including unusual
      facial appearance, mental retardation/developmental delay (MR/DD) (cases 3 and
      4), and syndactylies (case 1). The facial appearances of cases 1 and 3 were
      similar yet distinct from that of case 4. Using fluorescence in situ
      hybridization (FISH), each of the markers in these 4 cases was identified as
      having been derived from an X chromosome. The level of mosaicism for the mar/r(X)
      cell line in these cases varied from 70% (case 1) to 16% (case 4) but was not
      apparently correlated with the presence of MR/DD. Replication studies
      demonstrated a probable early replication pattern for the mar/r(X) in cases 1, 3,
      and 4, while the marker in case 2 was apparently late replicating. To date, 41
      individuals having mosaicism for a small mar/r(X) chromosome have been described.
      Interestingly, most of the 14 individuals having a presumedly active mar/r(X)
      demonstrated clinical findings atypical of UTS, including abnormal facial changes
      (11) and MR/DD (13). MR was noted most frequently in those cases having at least
      50% mosaicism for the marker or ring. In contrast, atypical UTS facial appearance
      or MR/DD was not noted in 14 of the 16 cases with UTS who carried a probable late
      replicating marker or ring. In conclusion, although the phenotype of
      45,X/46,X,mar/r(X) individuals appears to be influenced by the genetic content
      and degree of mosaicism for the mar/r(X), the most significant factor associated
      with MR/DD appears to be the activity status of the mar/r(X) chromosome. Thus,
      our 4 cases provide further support for the hypothesis that a lack of
      inactivation of a small mar/r(X) chromosome may be a factor leading to the MR and
      other phenotypic abnormalities seen in this subset of individuals having atypical
      UTS.

PMID- 7801997
TI  - Marked female predilection in some syndromes associated with facial hemangiomas.
AB  - Analysis of the literature yielded 42 examples of the combination of sternal non
      union and supraumbilical raphe without evidence of sex predilection. However,
      among an additional 31 cases in which the triad included facial hemangioma, there
      was almost exclusive female occurrence. Another condition involves extensive
      unilateral hemangioma of the face, absence of ipsilateral carotid and vertebral
      vessels, mental retardation, and Dandy-Walker malformation. Still another
      disorder has been proposed which includes facial hemangioma and dilatation of the
      carotid syphon. Both of these conditions exhibit marked female predilection.
      Examples of overlap of all three "disorders" cause the authors to question the
      independence of these disorders, hypothesizing instead that they represent a
      spectrum.

PMID- 7801999
TI  - Arylsulfatase A pseudodeficiency: a common polymorphism which is associated with
      a unique haplotype.
AB  - The allele for pseudodeficiency (PD) of the lysosomal enzyme arylsulfatase A
      (ARSA) is a common polymorphism in all populations. The PD allele frequency in
      different Israeli ethnic groups was found to range from 9.2-22.7%. The PD allele
      includes two different mutations PD(1) and PD(2) in an approximately 1 Kb
      interval. In this study we confirmed that while PD(1) may be found alone as a
      polymorphism, PD(2) is always associated with the PD allele (660 alleles
      screened). Analysis of three ARSA intragenic polymorphisms showed a complete
      linkage disequilibrium between the PD allele and an haplotype defined by the
      three polymorphic restriction sites. The results suggest that the origin of the
      PD polymorphism may be a common founder, or recurrent mutations which are
      occurring in a unique haplotype.

PMID- 7802000
TI  - Preimplantation genetics: a case for prospective action.
AB  - Preimplantation genetics describes a newly-emerging field in medical genetics,
      the consequence of the implementation of clinical preimplantation diagnosis and
      the likely future development of germ-line gene therapy. Given the existing
      clinical and laboratory difficulties already demonstrated in preimplantation
      diagnosis and the sensitive ethical issues surrounding genetic manipulation of
      human embryos, there is a need for 1) critical and objective evaluation of
      developments in this field by human and medical geneticists and 2) development of
      guidelines for research and clinical practice in the years ahead. We propose a
      course of prospective action for preimplantation genetics implemented through the
      newly-formed American College of Medical Genetics in order to address the ethics,
      safety, accuracy, cost, and overall merit of preimplantation genetics.

PMID- 7802001
TI  - Molecular and clinical study of 61 Angelman syndrome patients.
AB  - We analyzed 61 Angelman syndrome (AS) patients by cytogenetic and molecular
      techniques. On the basis of molecular findings, the patients were classified into
      the following 4 groups: familial cases without deletion, familial cases with
      submicroscopic deletion, sporadic cases with deletion, and sporadic cases without
      deletion. Among 53 sporadic cases, 37 (70%) had molecular deletion, which
      commonly extended from D15S9 to D15S12, although not all deletions were
      identical. Of 8 familial cases, 3 sibs from one family had a molecular deletion
      involving only 2 loci, D15S10 and GABRB3, which define the critical region for AS
      phenotypes. The parental origin of deletion, both in sporadic and familial cases,
      was exclusively maternal and consistent with a genomic imprinting hypothesis.
      Among sporadic and familial cases without deletion, no uniparental disomy was
      found and most of them were shown to inherit chromosomes 15 from both parents
      (biparental inheritance). A discrepancy between cytogenetic and molecular
      deletion was observed in 14 (26%) of 53 patients in whom cytogenetic analysis
      could be performed. Ten (43%) of 23 patients with a normal karyotype showed a
      molecular deletion, and 4 (13%) of 30 patients with cytogenetic deletion, del(15)
      (q11q13), showed no molecular deletion. Most clinical manifestations, including
      neurological signs and facial characteristics, were not distinct in each group
      except for hypopigmentation of skin or hair. Familial cases with submicroscopic
      deletion were not associated with hypopigmentation. These findings suggested that
      a gene for hypopigmentation is located outside the critical region of AS and is
      not imprinted.

PMID- 7802002
TI  - Cardiac abnormalities in the Bardet-Biedl syndrome: echocardiographic studies of
      22 patients.
AB  - The Bardet-Biedl syndrome is an autosomal recessive disorder of polydactyly,
      obesity, tapetoretinal degeneration, mental retardation, hypogenitalism, and
      renal involvement. A high incidence of congenital and acquired heart disease was
      reported in the former "Laurence-Moon-Biedl-Bardet" syndrome. However, since the
      establishment of the Bardet-Biedl syndrome as a separate clinical entity, cardiac
      involvement has not been evaluated in this disorder. We have performed
      echocardiographic studies on 22 patients with the Bardet-Biedl syndrome from
      three extended, highly inbred Bedouin families. In addition to previously
      reported congenital heart defects we have observed hypertrophy of the
      interventricular septum and dilated cardiomyopathy. Our findings of cardiac
      involvement in 50% of the cases suggest that echocardiographic examination should
      be included in the clinical evaluation and follow-up of patients with Bardet
      Biedl syndrome.

PMID- 7802003
TI  - Knobloch syndrome in a large Brazilian consanguineous family: confirmation of
      autosomal recessive inheritance.
AB  - Knobloch syndrome is a rare genetic disorder characterized by high myopia,
      vitreoretinal degeneration with retinal detachment and occipital cephalocele. The
      inheritance has been described as autosomal recessive (AR) but in addition to the
      original report with 5 affected patients [Knobloch and Layer, 1971] only one
      other family with 2 affected sibs has been described [Czeizel et al., 1992]. We
      have studied a large consanguineous kindred in which there are 12 patients with
      severe ocular alterations associated with a congenital occipital encephalocele,
      compatible with the diagnosis of Knobloch syndrome. CT scan and MRI performed in
      one of the patients, allowed a better understanding of the cranial and ocular
      alterations in this syndrome. The pattern of occurrence in this highly inbred
      family clearly confirms autosomal recessive inheritance of Knobloch syndrome.

PMID- 7802004
TI  - Apparent genetic homogeneity of the Treacher Collins-Franceschetti syndrome.
AB  - The Treacher Collins-Franceschetti syndrome (TCOF) or mandibulofacial dysostosis
      (MFD) is an autosomal dominant disorder characterized by craniofacial
      abnormalities and hearing loss. A refined genetic linkage map of the TCOF locus
      was established in 8 independent families, using 12 microsatellite DNA markers of
      the distal 5q. Positive lod score values were obtained for all markers with a
      maximum at the D5S413 locus (Zmax = 3.79 at theta = 0%). Multipoint linkage
      analysis and haplotype analysis supported the location of the gene between loci
      D5S434 and D5S412. These results are consistent with previous linkage analyses
      [Dixon et al.: Am J Hum Genet 49:17-22, 1991, Am J Hum Genet 52:907-914, 1993;
      Jabs et al.: Genomics 11:193-198, 1991, Genomics 18:7-13, 1993] and provide
      further evidence of genetic homogeneity in this syndrome.

PMID- 7802006
TI  - Duplication 10q confirmed by DNA in situ hybridization.
AB  - Partial duplication of 10q is a recognizable clinical entity. In most of the
      reported cases, the trisomic segment is identified by a balanced translocation
      state in a parent. Verification remains a problem in de novo cases. However, the
      recent availability of whole chromosome probes allows for confirmatory diagnosis
      of suspected cases. We describe a case of de novo duplication (10q) with
      verification using DNA in situ hybridization.

PMID- 7802005
TI  - Molecular cytogenetic determination of a deletion/duplication of 1q that results
      in a trisomy 18 syndrome-like phenotype.
AB  - We report on an infant who presented at birth with some characteristics of
      trisomy 18 syndrome, including low birth weight, facial abnormalities,
      overlapping fingers, and congenital heart defects. On chromosome analysis, no
      additional chromosome 18 was observed and both chromosome 18 homologues appeared
      normal. However, a small piece of chromosomal material of unknown origin was
      detected at the tip of the long arm of chromosome 1. Fluorescence in situ
      hybridization (FISH) using whole chromosome 18 painting probes disclosed no
      additional hybridization at the telomere of 1q, suggesting that the material was
      derived from another chromosome. Further chromosome painting experiments
      suggested that the telomeric addition was of chromosome 1 origin. To identify
      subchromosomal regions involved in the rearrangement, additional FISH analyses
      were performed using single copy and repetitive DNA probes mapping to different
      portions of chromosome 1. The analyses showed that probes mapping to 1q34-43 were
      duplicated in the derivative chromosome 1. In addition, a DNA probe mapping to
      1q44 was found to be deleted from the derivative chromosome 1. Our composite
      analysis suggests that a deletion and a duplication of chromosome 1q can result
      in some of the clinical findings usually associated with trisomy 18 syndrome.
      These results demonstrate the usefulness of FISH analysis when karyotype analysis
      is not consistent with the clinical description.

PMID- 7802007
TI  - Diamniotic placentation associated with omphalopagus conjoined twins:
      implications for a contemporary model of conjoined twinning.
AB  - We have studied omphalopagus conjoined twins with a diamniotic monochorionic
      placenta. Although conjoined twins usually present in a single amniotic sac, one
      other example of diamniotic placenta has been reported in omphalopagus twins
      [Weston et al., 1990: Am J Med Genet 37:558-561]. Most theories concerning the
      pathogenesis of conjoined twinning exclude the possibility of diamniotic
      placentation. However, Spencer [1992: Teratology 45:591-602] recently elaborated
      a model for conjoined twinning based on duplication of organizing centers
      (primitive streaks) during gastrulation. We have considered the fate of embryonic
      membranes according to this model of omphalopagus twinning and show that
      diamniotic placentation is a predictable outcome.

PMID- 7802008
TI  - Megalocornea-mental retardation syndrome: an additional case.
AB  - In 1975, Neuhauser (Z Kinderheilk 120:1-8) reported on a recessively inherited
      entity comprising mental retardation, megalocornea, and seizures. The
      megalocornea-mental retardation (MMR) syndrome (MIM 249310) is a rare entity.
      There have been 19 previously published cases and the clinical differences
      observed between reported patients have raised questions regarding the nosology
      of the syndrome and the issue of heterogeneity versus variability. We report on a
      new case: a 2 6/12-year-old boy, first child of nonconsanguineous healthy parents
      with megalocornea (corneal diameter > or = 13 mm), delayed psychomotor
      development and hypotonia, plus minor facial anomalies.

PMID- 7802009
TI  - Additional case of female monozygotic twins discordant for the clinical
      manifestations of Duchenne muscular dystrophy due to opposite X-chromosome
      inactivation.
AB  - A pair of female monozygotic (MZ) twins, heterozygous carriers for a deletion in
      the DMD gene and discordant for the clinical manifestations of Duchenne muscular
      dystrophy, were analyzed by molecular studies, in situ hybridization, and
      methylation pattern of X chromosomes to search for opposite X inactivation as an
      explanation of their clinical discordance. Results in lymphocytes and skin
      fibroblast cell lines suggest a partial mirror inactivation with the normal X
      chromosome preferentially active in the unaffected twin, and the maternal deleted
      X chromosome preferentially active in the affected twin. A review shows that MZ
      female twins discordant for X-linked diseases are not uncommon. Twinning and X
      inactivation may be interrelated and could explain the female twins discordant
      for X-linked traits.

PMID- 7802011
TI  - Jumping translocation in a newborn boy with dup(4q) and severe hydrops fetalis.
AB  - We report on the unusual cytogenetic findings in a newborn boy with severe
      hydrops fetalis. He has a mosaic for 2 unbalanced chromosome rearrangements: a
      der(18)-t(4;18)(q31;q23) and a der(18)t(4;18)(q31;p11). As a result, this patient
      had a duplication of 4q31-qter in all cells, and was possibly monosomic for the
      distal ends of 18p and 18q, respectively in the 2 cell lines. Since in both
      rearrangements the same chromosome 4 segment was translocated to 2 different
      chromosome regions, we consider the present finding as a peculiar type of jumping
      translocation.

PMID- 7802010
TI  - Linkage analyses of chromosome 6 loci, including HLA, in familial aggregations of
      Crohn disease. G.E.T.A.I.D.
AB  - Segregation analyses of familial aggregations of Crohn disease have provided
      consistent results pointing to the involvement of a predisposing gene with a
      recessive mode of inheritance. Although extensively investigated, the role played
      by human leucocyte antigen (HLA) genes in this inflammatory bowel disease remains
      elusive and the major histocompatibility complex is a candidate region for the
      mapping of the Crohn disease susceptibility gene. A total of 25 families with
      multiple cases of Crohn disease was genotyped for HLA DRB1 and for 16 highly
      polymorphic loci evenly distributed on chromosome 6. The data were subjected to
      linkage analysis using the lod score method. Neither individual nor combined lod
      scores for any family and for any locus tested reached values suggesting linkage
      or genetic heterogeneity. The Crohn disease predisposing locus was excluded from
      the whole chromosome 6 with lod scores less than -2. It was excluded from the
      major histocompatibility complex and from 91% of the chromosome 6 genetic map
      with lod scores less than -4. The major recessive gene involved in genetic
      predisposition to Crohn disease does not reside on the major histocompatibility
      complex nor on any locus mapping to chromosome 6.

PMID- 7802012
TI  - Discordant infantile encephalopathy with symmetrical thalamic calcifications in
      identical twins.
AB  - Connatal thalamic calcifications in apparently uneventful pregnancies have been
      described in various case reports and in a single report in two sibs. On the
      other hand, this lesion is known to occur after a hypoxic-ischemic accident in
      the immature brain. In the present report infantile encephalopathy with
      symmetrical thalamic calcifications is observed in one sib of a monozygous twin
      pair. This observation adds to the evidence that the condition is acquired, most
      probably on the basis of hypoxia-ischemia, and provides strong evidence against
      autosomal-recessive inheritance.

PMID- 7802013
TI  - Monozygotic twins discordant for gastroschisis: case report and review of the
      literature of twins and familial occurrence of gastroschisis.
AB  - We describe a pair of monozygotic (MZ) female twins discordant for gastrochisis.
      To our knowledge, this is the first such case reported. The zygosity was verified
      by DNA analysis using highly polymorphic microsatellites. There was no family
      history of gastroschisis. During pregnancy there was no suspicion of any exposure
      responsible for the malformation. The number of twin cases described so far does
      not allow any conclusion as to hereditary factors in the cause of gastroschisis,
      but the number of families reported with familial gastroschisis suggests that the
      recurrence risk is higher than previously thought.

PMID- 7802014
TI  - Intermittent hair loss in a child with PIBI(D)S syndrome and trichothiodystrophy
      with defective DNA repair-xeroderma pigmentosum group D.
AB  - We describe a girl with photosensitivity (P), ichthyosis (I), brittle hair (B),
      impaired intelligence (I), possibly decreased fertility (D), and short stature
      (S). The clinical findings fit into the PIBI(D)S syndrome and
      trichothiodystrophy. A remarkable and probably unique observation for this
      disorder was the intermittent character of the scalp hair loss during infectious
      periods in this patient. Easy suntanning suggested photosensitivity and prompted
      DNA repair studies which demonstrated reduced UV-induced DNA repair synthesis.
      Subsequent studies have assigned this patient to xeroderma pigmentosum group D
      and suggested a specific deficiency of 6-4 photoproduct repair. An unaffected
      child was diagnosed in the next pregnancy of the mother.

PMID- 7802016
TI  - Wiedemann-Beckwith syndrome, imprinting, IGF2, and H19: implications for
      hemihyperplasia, associated neoplasms, and overgrowth.

PMID- 7802015
TI  - Is fluphenazine a teratogen?

PMID- 7802017
TI  - Wiedemann-Beckwith syndrome: genomic imprinting revisited.

PMID- 7802018
TI  - Axial mesodermal dysplasia spectrum: affected sisters with oculoauriculovertebral
      "dysplasia" and caudal "regression" sequence.

PMID- 7802019
TI  - Detection of 46,XX male by Y-specific whole chromosome paint probe.

PMID- 7802020
TI  - Japanese kindred with FG syndrome.

PMID- 7802021
TI  - Double trisomy (48,XXX, +18)

PMID- 7802022
TI  - Blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES) and
      microcephaly.

PMID- 7802023
TI  - Angelman syndrome and vermian cyst.

PMID- 7802024
TI  - X-linked recessive fusion of metacarpals IV and V and hypoplastic metacarpal V.

PMID- 7802025
TI  - Familial Pallister-Hall syndrome: three affected offspring.

PMID- 7802026
TI  - Hereditary hemorrhagic telangiectasia: a disorder in search of the genetics
      community.

PMID- 7802027
TI  - NAS-NRC Twin Registry 1995 survey.

PMID- 7802028
TI  - Detection of sex chromosomal aneuploidies X-X, Y-Y, and X-Y in human sperm using
      two-chromosome fluorescence in situ hybridization.
AB  - Sex chromosome aneuploidy is the most common numerical chromosomal abnormality in
      humans at birth and a substantial portion of these abnormalities involve paternal
      chromosomes. An efficient method is presented for using air-dried smears of human
      semen to detect the number of X and Y chromosomes in sperm chromatin using two
      chromosome fluorescence in situ hybridization. Air-dried semen smears were pre
      treated with dithiothreitol and 3,4-diiodosalicylate salt to decondense the sperm
      chromatin and then were hybridized with repetitive sequence DNA probes that had
      been generated by PCR and differentially labeled. Hybridizations with X and Y
      specific probes showed the expected ratio of 50%X:50%Y bearing sperm. Sperm
      carrying extra fluorescence domains representing disomy for the X or Y
      chromosomes occurred at frequencies of approximately 4 per 10,000 sperm each.
      Cells carrying both X and Y fluorescence domains occurred at a frequency of
      approximately 6/10,000. Thus, the overall frequency of sperm that carried an
      extra sex chromosome was 1.4/1,000. The frequencies of sperm carrying sex
      chromosome aneuploidies determined by hybridization did not differ statistically
      from those reported from the same laboratory using the human-sperm/hamster-egg
      cytogenetic technique. Multi-chromosome fluorescence in situ hybridization to
      sperm is a promising method for assessing sex-ratio alterations in human semen
      and for determining the fraction of sperm carrying sex or other chromosome
      aneuploidies which may be transmissible to offspring.

PMID- 7802029
TI  - Lessons on objectivity in clinical studies.
AB  - Clinical assessments made with measuring devices are generally considered
      "objective" and "accurate" and are, therefore, more discriminating than
      subjective assessments. We show that the choice of measuring devices or non
      standardized landmarks to be used with the measuring devices affect the
      "accuracy" of the "objective" findings.

PMID- 7802030
TI  - OEIS complex with craniofacial anomalies--defect of blastogenesis?
AB  - We report on a 31-week fetus with hydrocephalus, hypertelorism, microtia, short
      neck, vertebral and rib defects, scoliosis, omphalocele, exstrophy of bladder,
      absent external genitalia and pubic rami, imperforate anus, diaphragmatic hernia,
      defective lobulation of lungs, single kidney, bicornuate uterus, and flexion
      deformities of the limbs. Similar extensive anomalies in the rostral and caudal
      regions were described by Russell et al. [Pediatrics, 67:176-182, 1981] and
      Stewart et al. [Am J Med Genet, 45:426-429, 1993]. The patients described by them
      had a combination of the oculo-auriculo-vertebral sequence (OAV) and caudal
      deficiency sequence, whereas the patient reported here can best be described as a
      combination of OAV and OEIS (omphalocele, exstrophy of bladder, imperforate anus,
      spinal defects) complexes. The widespread malformations seen in our patient may
      be the result of an error during blastogenesis.

PMID- 7802032
TI  - On the inheritance of the split hand/split foot malformation.
AB  - Analysis of families with non-syndromal split hand/split foot (SHSF) confirms the
      existence of 2 distinct entities, most probably caused by at least 2 different
      autosomal dominant genes. In the families in which the SHSF malformation is non
      syndromal and limited to the hands and feet (type I), the pattern of inheritance
      is of a regular autosomal dominant gene with a high penetrance (96%). In families
      in which at least one individual has other limb malformations and SHSF (type II),
      the transmission is often unusual. In most families, the gene is non-penetrant,
      sometimes for generations, before the birth of the first affected individual.
      Thereafter, among the descendants of affected individuals, the penetrance is
      reduced (66%), suggesting the possible existence of another gene which controls
      the appearance of the clinical manifestations. The possibility that SHSF
      associated with other limb malformations is a disorder caused by trinucleotide
      repeat instability is raised.

PMID- 7802031
TI  - Microscopic neuroblastoma in a fetus with a de novo unbalanced translocation
      3;10.
AB  - We report on a fetus with a de novo unbalanced translocation 3;10 and a
      microscopic neuroblastoma. The fetus had the karyotypic and phenotypic
      manifestations of partial dup (3q). The finding of a constitutional chromosomal
      abnormality and a microscopic neuroblastoma, although possibly coincidental,
      supports Knudson's two hit hypothesis for development of neuroblastomas and other
      embryonal tumors. In this case the first mutation is represented by the
      constitutional abnormality, possibly resulting in the microscopic neuroblastoma.
      A second mutation affecting the abnormal cells, which may be more prone to
      mutagenesis, may trigger a neuroblastoma.

PMID- 7802033
TI  - Recurrence of diaphragmatic agenesis associated with multiple midline defects:
      evidence for an autosomal gene regulating the midline.
AB  - We report the familial occurrence of diaphragmatic agenesis in association with
      other midline anomalies in a brother and sister. Opitz and Gilbert [Am J Med
      Genet 1982, 12:443-455] introduced the concept of the midline as a developmental
      field, and there have been reports of pedigrees compatible with the hypothesis of
      an X-linked gene regulating the development of the midline. This family suggests
      that an autosomal gene also contributes to the morphogenesis of midline
      structures.

PMID- 7802034
TI  - Partial X chromosome trisomy with functional disomy of Xp due to failure of X
      inactivation.
AB  - A 5-month-old girl with mild phenotypic abnormalities, developmental delay, and
      seizures was found to have the de novo karyotype 46,XX,
      13,+der(13)t(X;13)(p21.2;p11.1). The partial trisomy of Xp21.2-->pter was
      confirmed with fluorescence in situ hybridization, using an X chromosome painting
      probe and several cosmid and YAC probes for Xp sequences. Replication banding
      showed that one of the structurally normal X chromosomes was late-replicating,
      but that the Xp segment of the der(13) was early-replicating in all cells
      examined. Since segments of the X chromosome separated from the X inactivation
      center in Xq13.2 cannot undergo X inactivation, the result is functional disomy
      of distal Xp. As the loss of short arm material from chromosome 13 is not
      considered to be clinically significant, the genomic imbalance of Xp expressed in
      this patient most likely accounts for her abnormal phenotype.

PMID- 7802035
TI  - Holoprosencephaly associated with caudal dysgenesis: a clinical-epidemiological
      analysis.
AB  - We have studied 9 cases with the combination of some form of holoprosencephaly
      and any degree of caudal dysgenesis. The cases were identified through the
      Spanish Collaborative Study of Congenital Malformations (ECEMC). Of the 9 cases,
      6 infants had an aneuploidy syndrome, one had Meckel syndrome, and 2 cases were
      of unknown etiology. We determined that the prevalence figure for the association
      of both conditions in the same child was 0.08 per 10,000 livebirths, and 18.8
      times higher for stillbirths (i.e., 1.50/10,000). This prevalence is
      significantly higher than what would be expected by chance.

PMID- 7802037
TI  - Hypertrichosis "cubiti" with facial asymmetry.
AB  - Hypertrichosis of the elbow region may be the only abnormality in hypertrichosis
      cubiti (hairy elbow syndrome). Only 6 cases have been reported; 2 Amish sibs also
      had additional short stature and, in the most recent case report, a patient had
      asymmetry of the face, generalized hypotonia, ptosis, epicanthic folds, highly
      arched palate, and delayed growth and development. The child reported here also
      had asymmetry of facial growth, ptosis, delayed speech development, and
      hypertrichosis in a patchy distribution which included the elbow regions, face,
      trunk, and thighs. There was no family history of hypertrichosis, and the
      karyotype of cultured fibroblasts was normal in the skin of an area of
      hypertrichosis. These patients appear to have a distinct condition compared to
      other hypertrichosis syndromes.

PMID- 7802036
TI  - Monozygotic twins of different apparent sex.
AB  - We report on twins of unlike sex who shared a 45,X/46,X,+mar karyotype. The mar
      chromosome was found to be Yq- by DNA analysis. Marker studies, including 8 VNTR
      loci, yielded a probability of monozygosity of 0.99999996.

PMID- 7802038
TI  - Earliest description by Johann Friedrich Meckel, Senior (1750) of what is known
      today as Lutembacher syndrome (1916).
AB  - The letter that the famous anatomist Johann Friedrich Meckel, Sr. sent from
      Berlin on May 5, 1750 to the great Albrecht von Haller (at that time resident in
      Gottingen) contains the earliest reference to an unusual observation made by the
      former. Even today this observation is considered in the clinical literature to
      be the first description of a coarctation of the aorta. In fact, it is probably
      the first description of what is known today as Lutembacher syndrome.

PMID- 7802039
TI  - Clinical and linkage study of a large family with simple ectopia lentis linked to
      FBN1.
AB  - Simple ectopia lentis (EL) was studied in a large family, by clinical examination
      and analysis of linkage to markers in the region of FBN1, the gene for fibrillin
      which causes Marfan syndrome on chromosome 15. No patient had clinical or
      echocardiographic evidence of Marfan syndrome, although there was a trend towards
      relatively longer measurements of height; lower segment; arm span; middle finger,
      hand, and foot length in the affected members of the family, compared with
      unaffected sibs of the same sex. Analysis of linkage to intragenic FBN1 markers
      was inconclusive because they were relatively uniformative. Construction of a
      multipoint background map from the CEPH reference families identified
      microsatellite markers linked closely to FBN1 which could demonstrate linkage of
      EL in this family to the FBN1 region. LINKMAP analysis detected a multipoint lod
      score of 5.68 at D15S119, a marker approximately 6 cM distal to FBN1, and a
      multipoint lod score of 5.04 at FBN1. The EL gene in this family is likely to be
      allelic to Marfan syndrome, and molecular characterization of the FBN1 mutation
      should now be possible.

PMID- 7802040
TI  - Autosomal dominant Muckle-Wells syndrome associated with cystinuria, ichthyosis,
      and aphthosis in a four-generation family.
AB  - Muckle-Wells syndrome is a rare autosomal dominant disorder characterized by
      chronic recurrent urticaria, periodic arthritis, sensorineural deafness, general
      signs of inflammation, and secondary amyloidosis (AA type). We report on a 4
      generation family with 7 persons sharing various signs of this syndrome
      associated with bipolar aphthosis in 5 cases and cystinuria in one. Two other
      relatives in the family had ichthyosis.

PMID- 7802041
TI  - Second locus for Hirschsprung disease/Waardenburg syndrome in a large Mennonite
      kindred.
AB  - We have studied a large Mennonite kindred in which 20 members were affected with
      Hirschsprung disease (HSCR), 5 of whom had one or more manifestations of
      Waardenburg syndrome (WS) type II (WS2). Eleven additional relatives had signs of
      WS2 without HSCR. Since HSCR and WS2 each represent perturbations of neural crest
      migration/differentiation, this large pedigree with apparent cosegregation of
      HSCR and WS2 offered an opportunity to search for linkage between these loci,
      candidate genes, and random DNA markers, particularly in view of recent
      discoveries of genes for Waardenburg syndrome type I (WS1) and Hirschsprung
      disease (c-ret). We have examined the following possible linked markers in 69
      relatives in this family: the c-ret gene (HSCR); the human PAX3 gene (HuP2) on
      chromosome 2q (WS1) and placental alkaline phosphatase (ALPP) on chromosome 2q
      (linked to WS1); argininosuccinate synthetase (ASS) on chromosome 9q, close to
      ABO blood groups which have shown weak linkage to WS; and the beta 1 GABA
      receptor gene (GABARB1) on chromosome 4q13-11, close to c-kit, deletions of which
      cause piebaldism. Linkage between any of these loci and HSCR/WS in this kindred
      was excluded, demonstrating that there is at least one further locus for HSCR
      other than c-ret.

PMID- 7802042
TI  - Identification of marker chromosomes in thirteen patients using FISH probing.
AB  - Fourteen marker chromosomes were studied by FISH (fluorescence in-situ
      hybridization) in cytogenetic preparations from 13 patients. The derived markers
      were identified as one isodicentric bisatellited mar(22), one fragment sized
      r(X), one fragment sized r(Y), one i(18p), small autosomal ring markers in three
      different patients derived from chromosomes 2, 8, and 8, a marker comprised of 9p
      and part of 9qh, and 3 bisatellited apparently monocentric markers; one of each
      from chromosomes 13 or 21, 14 or 22, and 15. Two fragment sized small ring
      markers in one patient and a small ring marker in another were negative with all
      twenty-two different probes used. In addition, the small ring marker Y chromosome
      that was found in a boy with karyotype 46,X,-Y,+mar was negative with both pDXZ1
      and pDYZ3. This anomaly of negative results with the battery of centromeric
      alphoid probes can be explained if one breakpoint for some small ring markers is
      very near to or within the centromere. Only some of the pericentromeric
      repetitive sequences in the normal chromosome would be represented in the
      chromosome specific alphoid probes, and presumably those corresponding to the
      currently available probes are truncated during the formation of the unidentified
      markers. In three of the small ring markers the FISH signal on the marker was
      much stronger than on the normal homologues in various proportions of cells, and
      this may indicate that some of the fragment sized small rings were multicentric.
      The literature was reviewed for Distamycin A/DAPI negative small ring markers
      that were present as extra chromosomes. There were only single published cases of
      most small rings but there were three r(8) cases, two r(1) cases, two r(12)
      cases, and two r(20) cases, uncomplicated by the presence of other chromosome
      abnormalities. Most cases with similar small rings were quite dissimilar
      phenotypically and syndrome identification was not possible, but in pooled data,
      18/23 (about 80%) were developmentally and/or phenotypically abnormal. Some
      patients (5/23, about 20%) with small rings were dysmorphic without intellectual
      handicap. Of 28 such patients with small ring markers (Distamycin/Dapi negative)
      in pooled data there are 6 (about 20%) with multiple markers mostly derived from
      different chromosomes. This is a very high figure and would suggest that the ring
      formation events, although involving different chromosomes, must be related and
      must be an indicator of the mechanism of origin of this group of markers.

PMID- 7802043
TI  - Brachytelephalangic chondrodysplasia punctata in an extremely premature infant.

PMID- 7802044
TI  - "Autistic" behavior in two children with Williams-Beuren syndrome.

PMID- 7802045
TI  - Varadi syndrome or Opitz trigonocephaly: overlapping manifestation in two
      cousins.

PMID- 7802046
TI  - Ectrodactyly and 7q22.1.

PMID- 7802047
TI  - Esophageal stenosis in acrocephalosyndactyly type I.

PMID- 7802048
TI  - Trisomy 18 mosaicism in a 24-year-old white woman with normal intelligence and
      skeletal abnormalities.

PMID- 7802049
TI  - New Pvu II mitochondrial polymorphism in a mother and son of Indian ancestry.

PMID- 7802050
TI  - Surgical management of prolapse of the anterior vaginal segment: an analysis of
      support defects, operative morbidity, and anatomic outcome.
AB  - OBJECTIVES: The objectives of this study were to describe a group of women with
      prolapse of the anterior vaginal segment associated with bilateral paravaginal
      defects, to report the morbidity associated with the operative repair, and to
      analyze the results of preoperative and postoperative pelvic support defects in
      five vaginal sites. STUDY DESIGN: Between June 1, 1988, and Nov. 3, 1993, 62
      consecutive women with prolapse of the anterior vaginal segment associated with
      bilateral periurethral and perivesicle support defects and other coexisting
      pelvic support defects were treated by paravaginal repair done via the vagina and
      total pelvic reconstruction. Site-specific analysis of support for the urethra,
      bladder, cervix or cuff, cul-de-sac, and rectum was performed preoperatively, 6
      weeks postoperatively, and longitudinally to assess the anatomic outcome of
      surgery. Perioperative morbidity was defined as hemorrhage requiring homologous
      blood transfusion, pelvic nerve injury, deep venous thrombosis, visceral injury,
      or infection. RESULTS: One hundred percent of the study patients had preoperative
      evidence of bilateral paravaginal defects, and 87% had a prolapse of the anterior
      segment that was halfway to completely outside the hymen. Seven patients
      experienced perioperative morbidity none of which was unique to this procedure.
      Fifty-six patients have been followed up a mean of 1.6 years postoperatively. In
      four, anterior segment defects have developed to or through the hymen, although
      none is as large as the preoperative defect and none has required further surgery
      to date. In one patient a postoperative defect developed in the cul-de-sac
      extending to the hymen; she has had the defect repaired and has been followed up
      1.7 years with no support defects. CONCLUSION: Paravaginal repair performed
      transvaginally is a safe, effective method of management of prolapse of the
      anterior vagina associated with paravaginal defects. Coexisting support defects
      that require specific identification and repair can also be managed vaginally.

PMID- 7802051
TI  - Ovarian remnant syndrome: study in laboratory rats.
AB  - OBJECTIVES: This study was designed to answer two questions: (1) will
      devascularized ovarian rat tissue reimplant on intact or denuded peritoneal
      surfaces, and (2) will any revascularized tissue become functional, as evidenced
      by follicle formation and vaginal cornification? STUDY DESIGN: A total of 110
      young female Sprague-Dawley rats were divided into four study groups and a
      control group. Bilateral oophorectomy was performed on the rats in the first
      three study groups. In these groups the ovaries were sutured to the left
      peritoneal surfaces, where the devascularized tissue might become revascularized.
      The vascularized ovary was sutured to the right denuded peritoneal surface in the
      rats in group 4, and an oophorectomy was performed on the rats in the control
      group. The study animals were killed and evaluated at 3, 6, or 9 weeks
      postoperatively. RESULTS: Seventy-five percent of the devascularized ovarian
      tissue revascularized. Forty-three percent of the viable ovarian tissue
      demonstrated follicular growth that increased with time to death. Thirty-seven
      percent of the rats showed the effects of estrogen on the vaginal epithelium.
      CONCLUSIONS: This study indicates that devascularized ovarian tissue may
      reimplant on intact or abraded peritoneal surfaces, where in time it may resume
      functioning. These findings suggest that great care must be taken when using the
      laparoscope to collect ovarian specimens.

PMID- 7802052
TI  - Repair of vaginal vault prolapse by suspension of the vagina to iliococcygeus
      (prespinous) fascia.
AB  - OBJECTIVES: We reviewed our experience with the use of iliococcygeus fascia for
      repair of vaginal vault prolapse. STUDY DESIGN: A retrospective chart review
      identified 110 patients who had repair of vaginal vault prolapse by suspension of
      the vagina to iliococcygeus fascia from March 1981 to April 1991. All patients
      were followed for a minimum of 3 years. RESULTS: Thirty-seven (33.6%) patients
      had uterine prolapse with enterocele. Posthysterectomy enterocele was present in
      73 (66.4%) patients. All had a complex pelvic floor defect including cystocele or
      rectocele. Mean age was 54.5 +/- 14.6 years and mean parity was 4.1 +/- 3.2
      births. Forty-two (38%) were grand multiparous patients. Five were nulliparous.
      Length of the procedure was 163.2 +/- 11.4 minutes. Estimated blood loss was
      358.2 +/- 253.6 ml. Postoperative urinary catheterization was required for 6.1 +/
      4.1 days. Duration of hospital stay was 5.5 +/- 2.0 days. Three patients had
      hemorrhage > 750 ml and two required transfusion. One bowel injury and one
      bladder injury occurred. Forty-one patients had postoperative complications. The
      patients have been followed up for a minimum of 3 years, and four have had
      recurrent defects. All recurrent defects involved the anterior vaginal wall.
      CONCLUSIONS: Suspension of the vagina to the iliococcygeus fascia for repair of
      vaginal vault prolapse provides excellent long-term results. Critical to the
      success of vaginal vault suspension are adequate dissection and repair of all
      fascial defects. Adequate repair of the perineal body also plays a pivotal role.
      The anterior vaginal wall remains susceptible to recurrence.

PMID- 7802053
TI  - Basic laparoscopic knowledge among gynecologic laparoscopists.
AB  - OBJECTIVE: Our purpose was to assess the basic knowledge of laparoscopy and
      laparoscopic sterilization among gynecologic laparoscopists. STUDY DESIGN: A four
      part multiple-choice test designed for use in residency training, covering basic
      aspects of laparoscopy and laparoscopic sterilization, was distributed to 155
      registrants at a gynecologic surgery postgraduate course. Test results were
      compared among subgroups, as well as with results for 23 residents who had taken
      the test before their rotation in laparoscopic sterilization. RESULTS: Residents
      scored higher than practitioners on all test segments. No practitioner achieved
      the 85% correct passing score required of residents. Practitioner scores did not
      increase as the number of laparoscopic sterilizations performed per year
      increased, but higher test scores were associated with more recent completion of
      residency. CONCLUSION: Basic knowledge of laparoscopic sterilization among
      practicing gynecologists, as measured by a test designed for residents, is less
      than that of the residents.

PMID- 7802054
TI  - Urinary complaints after modified Burch urethropexy: an analysis.
AB  - OBJECTIVE: Postoperative bladder complaints after incontinence procedures are
      well known to the pelvic surgeon, but there are few reports comparing subjective
      complaints with objective data. Thirty of 68 patients who underwent a modified
      Burch urethral suspension were interviewed and examined by the first author. Four
      channel urodynamics were then performed. STUDY DESIGN: Of the 30 patients, eight
      (27%) complained of postoperative urinary leaking, and three of eight (10%) said
      they leaked worse than before surgery. Four patients (13%) had objective evidence
      of detrusor instability on cystometrogram. Two patients (6%) had recurrent
      genuine stress incontinence. No patients had bladder spams or symptoms of
      retention. Univariate and multivariate analyses were performed on the following
      preoperative patient factors in relation to surgical success: age, height,
      hormonal status, and concurrent pelvic relaxation. Only preoperative hormone use
      had statistical significance in relation to surgical success. RESULTS: The eight
      patients with leaking were treated on the basis of subjective complaints plus
      objective findings. The patients with detrusor instability had improvement with
      medication and bladder drills, but two of the four still had mild leakage. Of the
      other four patients, one required a urethral sling and is now dry. The other
      three patients had significant improvement or cure of symptoms after
      modifications were made in their voiding techniques. CONCLUSION: Our study
      suggests that preoperative and postoperative estrogen use is significantly
      correlated with surgical success of the Burch procedure, whereas age, weight, and
      postoperative pelvic relaxation have little influence. We also found that
      surgical success could be improved by close evaluation and individual management
      of patients with voiding complaints.

PMID- 7802055
TI  - Clinical features of urinary incontinence and urogenital prolapse in a black
      inner-city population.
AB  - OBJECTIVE: Our purpose was to describe the clinical features and urodynamic
      findings of a black female inner-city population with urinary incontinence and
      uterovaginal prolapse. STUDY DESIGN: A retrospective review of the urogynecoloy
      records of 159 black female patients was performed. RESULTS: Genital prolapse was
      common. A cystocele was identified in 116 patients, a rectocele in 88 patients,
      and uterine or vaginal vault prolapse in 41 patients. Subtracted multichannel
      cystometry revealed detrusor overactivity in 58 patients, genuine stress
      incontinence in 44 patients, and mixed incontinence in 30 patients. Sixteen
      patients had normal urodynamic studies. The presence of a cystocele and the
      physical sign of stress incontinence at initial examination were found equally in
      patients with genuine stress incontinence, detrusor instability, and mixed
      incontinence at cystometry. There was no correlation between other commonly
      associated clinical factors (such as age, parity, and obesity) and the urodynamic
      diagnosis. CONCLUSIONS: Many of the factors commonly assumed to predispose women
      to the development of incontinence and prolapse may not apply to the black inner
      city population. Urodynamic testing to establish the correct diagnosis is
      required, because the correlation between symptoms, physical examination, and
      urodynamic findings is relatively poor in this population.

PMID- 7802056
TI  - Simple bladder filling with a cough stress test compared with subtracted
      cystometry for the diagnosis of urinary incontinence.
AB  - OBJECTIVE: Our purpose was to compare the diagnostic efficacy of observing urine
      loss during simple bladder filling (without pressure measurement) and a cough
      stress test, with multichannel subtracted cystometry. STUDY DESIGN: The
      urodynamic records of 77 women complaining of urinary incontinence were reviewed.
      All women had undergone a full evaluation that included a standardized history
      and physical examination, urinalysis and urine culture, uroflowmetry with
      measurement of postvoid residual urine, a cough stress test performed during and
      after simple retrograde bladder filling, and multichannel subtracted cystometry.
      The results of simple bladder filling and the cough stress test were recorded as
      "urge incontinence," "stress incontinence,"mixed incontinence," or "incontinence
      not demonstrated." The subtracted cystometrogram was then performed, and the
      urodynamic diagnoses were recorded as "detrusor instability," "genuine stress
      incontinence," "mixed incontinence," or "incontinence not demonstrated." The
      records were reviewed, and the results of simple bladder filling with a cough
      stress test were compared with those obtained by subtracted multichannel
      provocative cystometry. RESULTS: With the subtracted multichannel cystometrogram
      used as the "gold standard" for diagnosis, the demonstration of "urge
      incontinence" during simple bladder filling had a sensitivity of 64% and a
      specificity of 86.8% for the demonstration of detrusor instability during
      cystometry, with a positive predictive value of 83.3% and a negative predictive
      value of 70.2%. The demonstration of "stress incontinence" during simple bladder
      filling had a sensitivity of 88.1% and a specificity of 77.1% for the
      demonstration of "genuine" stress incontinence during cystometry, with a positive
      predictive value of 82% and a negative predictive value of 84.4%. CONCLUSIONS:
      The demonstration of urge incontinence during simple bladder filling is a
      reliable predictor of detrusor instability, but its absence is less reliable in
      excluding detrusor overactivity as a cause of urinary incontinence. Similarly,
      the clinical demonstration of stress incontinence during simple bladder filling
      is predictive of the presence of "genuine" stress incontinence during subtracted
      multichannel provocative cystometry. The inability to demonstrate stress
      incontinence during simple bladder filling is highly correlated with the absence
      of "genuine" stress incontinence during complex urodynamic testing. Simple
      bladder filling is a reliable method of diagnosing urinary incontinence. In many
      cases it can replace complex urodynamic testing, particularly if the proposed
      treatment for the condition carries a low level of risk, and is helpful in
      selecting patients who need more extensive evaluation.

PMID- 7802057
TI  - Outpatient hysterectomy: determinants of discharge and rehospitalization in 133
      patients.
AB  - OBJECTIVE: This study examines our continuing experience in performing vaginal
      hysterectomies and laparoscopy-assisted vaginal hysterectomies with an outpatient
      protocol. The purpose was to review factors associated with discharge and
      hospitalization. STUDY DESIGN: Surgical records from all women entering our
      previously reported outpatient hysterectomy protocol were reviewed. Demographics,
      surgical indications, intraoperative data, and postoperative data were studied,
      and their associations with patient discharge and hospitalization were
      determined. Specific attention was directed to complications. RESULTS: The study
      group consisted of 133 women. Twelve women (9.0%) were not discharged from the
      hospital and 5 (3.8%) required readmission. Surgical indications, the type of
      hysterectomy, and the requirement for pain medication revealed no association
      with hospitalization. The occurrence of an intraoperative complication (p <
      0.000), the need for transfusion (p = 0.043), and postoperative antiemetics (p =
      0.013) were statistically associated with hospitalization. In addition, low
      hematocrit values and elevated temperatures on the first and second postoperative
      days were associated with hospitalization. CONCLUSION: Long-term experience with
      outpatient hysterectomy reveals a hospitalization rate of 12.8%. Complications,
      blood loss, elevated temperatures, and postoperative nausea are the major
      determinants of patient discharge and hospitalization. Readmission rates continue
      to remain low.

PMID- 7802058
TI  - Surgical treatment of endometriosis-associated infertility: meta-analysis
      compared with survival analysis.
AB  - OBJECTIVE: Our purpose was to evaluate the role of surgery in the treatment of
      endometriosis associated with infertility. STUDY DESIGN: We used a prospective
      cohort analysis of pregnancy rates and variables affecting pregnancy rates for
      surgical, medical, and no treatment. Our studies were combined with those
      reported by Hughes et al. (Fertil Steril 1993; 59:963-70), and the meta-analysis
      was expanded to include additional comparisons. Treatment was performed by a
      single surgeon in a referral reproductive endocrinology and surgery private
      practice. Results from 579 women with endometriosis and infertility in our study
      and the meta-analysis of 25 studies by Hughes et al. were examined. Interventions
      consisted of no treatment, medical treatment, or surgical treatment by
      laparoscopy or laparotomy. The main outcome measure was pregnancy rates. RESULTS:
      For minimal and mild disease, no treatment, laparoscopy, and laparotomy had
      equivalent 3-year estimated cumulative life-table pregnancy rates (67% +/- 12%,
      68% +/- 4%, and 74% +/- 8%, respectively) that were higher than medical treatment
      pregnancy rates (Breslow p = 0.003). For moderate and severe disease, all but 11
      patients were treated surgically. The 3-year estimated cumulative life-table
      pregnancy rates were 62% + 6% [corrected] for 120  laparoscopy cases and 44% + 6%
      [corrected] for 102 laparotomy cases (Breslow p = 0.054). For endometriomas, 48
      laparoscopy patients had a 3-year estimated cumulative life-table pregnancy rate
      of 52% +/- 9% and 52 laparotomy patients had a 3-year estimated cumulative life
      table pregnancy rate of 46% +/- 9% (Breslow p = 0.48). For 28 patients with
      complete cul-de-sac obliteration, the 3-year estimated cumulative life-table
      pregnancy rates were 30% +/- 14% after laparoscopy and 24% +/- 12% after
      laparotomy (Breslow p = 0.084). Comparison of our results with the expanded meta
      analysis revealed deficiencies in the design of meta-analysis studies and the
      impact of our using life-table pregnancy rates controlled for factors influencing
      outcome (survival analysis with fixed covariates) rather than the simple
      pregnancy rates used in the meta-analysis. Benefits of sophisticated statistical
      techniques, including propensity scores, to adjust for noncomparability of groups
      in prospective cohort studies were identified. CONCLUSION: Both our study and the
      meta-analysis show that either no treatment or surgery is superior to medical
      treatment for minimal and mild endometriosis associated with infertility. For
      moderate and severe disease, surgery is usually used. In these patients
      experienced surgeons utilizing good clinical judgment can achieve results at
      operative laparoscopy at least equivalent to those at laparotomy, even in cases
      involving endometriomas and complete cul-de-sac obliteration. Prospective
      randomized trials should be performed to confirm these findings.

PMID- 7802059
TI  - Adnexal torsion: can the adnexa be saved?
AB  - OBJECTIVE: Our purpose was to identify which cases of adnexal torsion may be
      managed with adnexal conservation. STUDY DESIGN: A retrospective chart review was
      conducted on all patients diagnosed with adnexal torsion between February 1983
      and February 1993 at four hospitals in the Emory University system. RESULTS:
      Fifty-nine patients ranging in age from 23 months to 73 years (mean 31.9 years)
      were reviewed. Almost half of the patients were nulliparous. Lower abdominal pain
      (83%) and an adnexal mass (72%) were the most common presenting findings, but in
      general clinical findings were nonspecific. Most patients were treated with
      extirpative therapy of the affected adnexa. Untwisting of the adnexa was
      performed in 10 patients; however, adnexal conservation was accomplished in only
      one patient. There were no thromboembolic complications in any of the patients.
      CONCLUSIONS: Adnexal torsion is a diagnostic challenge, often with nonspecific
      symptoms. There is growing evidence that untwisting the involved adnexa to
      observe for tissue reperfusion and viability is safe. However, significant delay
      in surgical intervention may result in irreversible tissue necrosis, rendering
      the adnexa unsalvageable.

PMID- 7802061
TI  - Long-term analysis of the surgical management of pelvic support defects.
AB  - OBJECTIVE: The aim of this study was to determine the success of various
      procedures to correct defects of pelvic support and to elucidate the role of
      sacrospinous ligament fixation in primary versus nonprimary vaginal operations.
      STUDY DESIGN: This study was a retrospective analysis, covering 23 years, of 486
      patients treated for pelvic support defects, grouped according to the location
      and severity of the defect, type of repair, and outcome. RESULTS: For primary
      repairs the recurrences were more frequent the more severe the defect, but this
      relationship did not hold for repeat surgery. Sacrospinous ligament fixation,
      when performed concurrently with vaginal hysterectomy for patients with third
      degree prolapse in primary cases reduced the rate of recurrence from 15.8% to
      6.7%. CONCLUSION: The original degree and type of pelvic support defect is
      important in selecting the appropriate operative procedure for the highest
      likelihood of cure. There may be a wider role for sacrospinous ligament fixation
      in primary operations for patients with severe defects.

PMID- 7802060
TI  - Deoxyribonucleic acid ploidy and S-phase fraction are not significant prognostic
      factors for patients with cervical cancer.
AB  - OBJECTIVE: Our purpose was to determine the usefulness of deoxyribonucleic acid
      ploidy and S-phase fraction as prognostic factors in patients with cervical
      cancer. STUDY DESIGN: Paraffin-embedded tumor specimens were obtained from 123
      patients with cervical cancer (mean age 51 years, range 21 to 87 years). The mean
      follow-up period was 6.4 years. Deoxyribonucleic acid ploidy and S-phase fraction
      were determined by flow cytometry. RESULTS: A total of 119 patients were
      evaluable for deoxyribonucleic acid ploidy and 92 were evaluable for S-phase
      fraction. The overall rate of deoxyribonucleic acid aneuploidy was 60%, and the
      median S-phase fraction was 12.5%. Neither factor was significantly related to
      stage of disease. In univariate survival analyses patients with deoxyribonucleic
      acid aneuploid tumors had slightly better early survival than did patients with
      deoxyribonucleic acid diploid tumors (median survivals 2.7 and 1.4 years,
      respectively, p = 0.08 [Wilcoxon]), but the overall survival was not
      significantly different, p = 0.37 (log-rank). In multivariate analyses
      deoxyribonucleic acid ploidy was not a significant predictor of survival. S-phase
      fraction was not statistically significant in either analysis. CONCLUSION:
      Deoxyribonucleic acid ploidy and S-phase fraction are not useful prognostic
      factors for patients with cervical cancer.

PMID- 7802062
TI  - The morning-after pill--how long after?
AB  - Postcoital contraception has been prescribed for more than two decades. The
      current regimen is given within 72 hours of unprotected intercourse. After this
      period, not many choices remain; either the woman may wait until her next menses
      hoping she is not pregnant or she may have a postcoital intrauterine
      contraceptive device inserted. Since these alternatives are not always
      acceptable, we reviewed the literature looking for evidence supporting the
      current maximum time limit for treatment. Our conclusion is that the limit could
      theoretically be extended; therefore we think it is time to challenge the time
      period of current treatment by conducting clinical trials.

PMID- 7802063
TI  - Na+ transport, H+ concentration gradient dissipation, and system A amino acid
      transporter activity in purified microvillous plasma membrane isolated from first
      trimester human placenta: comparison with the term microvillous membrane.
AB  - Our purpose was to isolate microvillous plasma membrane from first-trimester
      placenta and to measure its transport properties with regard to Na+, H+, and a
      neutral amino acid. Microvillous membrane was isolated from first-trimester (10
      to 13 weeks) and term (38 to 42 weeks) placenta and the purity determined. Uptake
      of 22Na+ was measured in the presence of an outwardly directly H+ gradient in the
      presence or absence of amiloride (0.5 mmol/L). The rate of dissipation of an H+
      concentration gradient was determined with the H(+)-sensitive fluorescent probe
      2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein. 14C-methylaminoisobutyric acid
      uptake was measured in the presence and absence of an inwardly directed Na+
      gradient. Purity, vesicle volume, vesicle orientation, and electron micrographic
      appearance of the first-trimester membranes were similar to those obtained from
      term placenta, but vesicle protein recovery was lower. Amiloride-sensitive Na+
      uptake and Na(+)-dependent 14C-methylaminoisobutyric acid uptake was threefold to
      fourfold lower by first-trimester than by term membranes. The rate of H+
      concentration gradient dissipation was greater in the former. The first-trimester
      microvillous membrane has similar general characteristics to that from term
      placenta, but its transport activity is quite different.

PMID- 7802064
TI  - Accuracy of the middle-cerebral-to-umbilical-artery resistance index ratio in the
      prediction of neonatal outcome in patients at high risk for fetal and neonatal
      complications.
AB  - OBJECTIVE: The purpose of this study was to determine the accuracy of the middle
      cerebral-to-umbilical-artery resistance index ratio in the prediction of fetal
      outcome in pregnancies at high risk for fetal and neonatal morbidity and
      mortality. STUDY DESIGN: A prospective controlled nonrandomized study was
      conducted in the high-risk pregnancy unit of a teaching hospital. The control
      group was formed by 20 healthy women with uncomplicated singleton pregnancies and
      healthy children delivered at term. The study group consisted of 115 women
      referred to the high-risk pregnancy unit because of a variety of pregnancy
      complications. Longitudinal evaluation of the control group and cross-sectional
      evaluation of the study group were carried out at different gestational ages by
      means of duplex Doppler ultrasonography. The main outcome measures were fetal
      growth retardation, preterm birth, and neonatal morbidity. RESULTS: The middle
      cerebral-to-umbilical-artery ratio remains relatively constant (mean +/- SD 1.33
      +/- 0.19) between 27 and 37 weeks. A cutoff value of 1.0 (sensitivity 57.9%,
      specificity 75.6%, false-positive rate 24.4%) was selected from the receiver
      operator characteristic curve analysis. This cutoff value successfully identified
      a population at significant risk of fetal growth retardation (relative risk 3.07,
      95% confidence interval 1.73 to 5.45, exact two-tailed p = 0.0009) and severe
      neonatal morbidity (Mann-Whitney U = 463.5, two-tailed p = 0.03). The middle
      cerebral-to-umbilical-artery ratio was not useful in the prediction of preterm
      birth. CONCLUSIONS: A middle-cerebral-to-umbilical-artery ratio of < or = 1.0
      identifies a subgroup of patients at high risk for fetal growth retardation and
      severe neonatal morbidity.

PMID- 7802065
TI  - Air contamination in umbilical cord blood gas sampling.
AB  - OBJECTIVE: Our purpose was to determine the effect of air contamination and the
      length of time before assay on umbilical cord blood gases at delivery. STUDY
      DESIGN: Umbilical venous cord blood gases (0.5 ml) were drawn from 21 patients at
      delivery in 1 and 3 ml heparinized syringes with varying amounts of air
      contamination (none, 0.5 ml air admitted and removed from the syringe, and 0.5 ml
      of air retained). In an additional 15 patients the 0.5 ml sample was contaminated
      with 0.1, 0.2, 0.3, 0.4, and 0.5 ml of air. RESULTS: Air contamination had no
      effect on pH, PCO2, or bicarbonate but did increase the PO2 when the residual air
      was > 37.5% in a 3 ml syringe. No changes occurred in a 1 ml syringe. Time from
      drawing the blood to assay did not significantly alter the results. CONCLUSION:
      Umbilical cord blood gases are best drawn in 1 ml heparinized syringes. Only if
      the residual air contamination exceeds 37.5% will PO2 increase. The level of air
      contamination will not alter the evaluation of fetal-neonatal acidosis.

PMID- 7802066
TI  - Regional blood flow and metabolism in ovine fetuses during severe cord occlusion.
AB  - OBJECTIVE: Our purpose was to compare the ovine fetal response to severe,
      damaging asphyxia resulting from umbilical cord occlusion with that seen in
      uterine artery occlusion. STUDY DESIGN: Six ovine fetuses were exposed to severe
      asphyxia produced by partial umbilical cord occlusion for 90 minutes. Fetal blood
      pressure and heart rate, blood gases, acid base status, electrocorticogram, and
      electromyogram were recorded. Regional blood flow (radioactive microspheres)
      measurements were performed at control and 30, 60, and 90 minutes of occlusion
      and 30 minutes after release. RESULTS: During the period of occlusion pH fell
      from 7.37 +/- 0.01 (mean +/- SEM) to 6.82 +/- 0.03 at 90 minutes, base excess
      from 5 +/- 1 to -22 +/- 2 mEq.L-1 and oxygen content from 3.3 +/- 0.4 mmol.L-1 to
      a nadir of 1.6 +/- 0.4 mmol.L-1 (p < 0.05). There was no significant long-term
      change in fetal heart rate or blood pressures. The fetal electrocorticogram was
      profoundly suppressed during asphyxia, and seizure activity was documented after
      release of occlusion in all surviving animals. Umbilical blood flow fell to 21%
      +/- 5% of control by 60 minutes of occlusion and remained depressed until
      release. Brain and adrenal blood flows increased during asphyxia. Heart and
      intestinal blood flows did not change significantly from control values. Combined
      ventricular output and spleen, kidney, and carcass blood flow fell during the
      insult. Oxygen uptake by the cerebral cortex remained stable during occlusion.
      Oxygen uptake by the lower carcass fell to 15% +/- 7% of control. CONCLUSION:
      Umbilical cord occlusion produces similar levels of asphyxia and evidence of
      encephalopathy (seizures), compared with previous experiments with uterine artery
      occlusion. The fetal response with respect to blood flow redistribution and organ
      oxygen uptake, however, differs. These differences may signify that with uterine
      artery occlusion the brain may be more vulnerable, whereas with umbilical cord
      occlusion the heart may be at greater risk.

PMID- 7802067
TI  - Effect of maternal cocaine abuse on renal arterial flow and urine output of the
      fetus.
AB  - OBJECTIVE: Our purpose was to study the short-term effect of maternal cocaine
      abuse on blood flow of the fetal kidney and the fetal hourly urine output. STUDY
      DESIGN: Thirty-three pregnant patients of various gestational ages with a history
      of cocaine abuse were studied. Patients were included if the urine specimen was
      positive for cocaine on the day of study. Patients were excluded if the urine
      specimen was positive for any other vasoactive substances or medications. Color
      and pulsed wave Doppler studies were used to obtain the flow velocity waveform of
      the fetal renal artery. The resistance index was calculated from systolic and
      diastolic values of flow velocity waveforms, Longitudinal, transverse, and
      anteroposterior diameters of the fetal urinary bladder were measured from
      transverse and coronal images at their maximum diameters, and the bladder volume
      was calculated. The hourly urine output of the fetus was measured from the
      difference in the bladder volume at half-hour intervals. As controls, 110 normal
      pregnancies between 19 and 40 weeks were similarly studied for normal values. The
      resistance index of the fetal renal artery and the hourly fetal urine output of
      the two groups were compared. RESULTS: The resistance index of the fetal renal
      artery of normal pregnancies had a negative association with gestational age (p <
      0.05). Cocaine-exposed fetuses had a significantly higher resistance index of the
      renal artery (p < 0.01) than did normal fetuses of corresponding gestational
      ages. A decrease in the hourly urine output of cocaine-exposed fetuses was
      observed, compared with normal controls of corresponding gestational ages (p <
      0.001). CONCLUSION: The resistance index values of fetal renal artery and fetal
      urine output were affected by maternal cocaine abuse.

PMID- 7802068
TI  - Effects of hypobaric hypoxia on the fetoplacental unit: the morphometric
      diffusing capacity of the villous membrane at high altitude.
AB  - OBJECTIVE: Our purpose was to determine whether the human placenta is able to
      adapt structurally to hypobaric hypoxia so as to increase its diffusing capacity.
      STUDY DESIGN: Material from 10 normal term placentas collected at each of three
      altitudinal levels in Kirghizstan was analyzed stereologically. Data were
      compared by one-way analysis of variance. RESULTS: Within the overall sample
      group birth weight and placental weight remained constant. There were no
      differences in villous and capillary surface areas or capillary length, but
      capillary volume increased from 37.9 cm3 in controls (700 m) to 50.8 cm3 at high
      altitude (2200 to 2800 m). The harmonic mean thickness fell from 6.9 microns in
      controls to 4.8 microns at high altitude. Consequently, the morphometric
      diffusing capacity of the villous membrane for oxygen increased from 4.22 to 7.56
      cm3.min-1.mm Hg-1 (F = 6.45, p < 0.05). CONCLUSIONS: The placenta is capable of
      adapting to hypobaric hypoxia to increase its functional capacity for gaseous
      exchange. This is principally through a reduction in the thickness of the villous
      membrane.

PMID- 7802069
TI  - Reduction of annexin-V (placental anticoagulant protein-I) on placental villi of
      women with antiphospholipid antibodies and recurrent spontaneous abortion.
AB  - OBJECTIVE: The mechanism by which antiphospholipid antibodies are associated with
      pregnancy loss and thromboembolic conditions has yet to be elucidated. Annexin-V,
      an anticoagulant phospholipid-binding protein, is normally present in
      syncytiotrophoblasts lining the placental villi, where it may play a role in the
      maintenance of intervillous blood fluidity. We therefore investigated the
      distribution of annexin-V in placentas of patients with antiphospholipid
      antibodies in situ and then used short-term villous cultures to study the direct
      effect of antiphospholipid antibodies on the immunolocation of annexin-V. STUDY
      DESIGN: We performed a blinded study by means of computerized morphometric
      analysis of placental tissues that were stained for annexin-V with affinity
      purified polyclonal antibody in an avidin-biotin peroxidase system. The
      distribution of villous surface annexin-V on cross sections of placentas of
      patients with antiphospholipid antibodies was compared with that of placentas
      from patients with uncomplicated pregnancies, elective abortions, and pregnancy
      losses not associated with antiphospholipid antibodies (n = 8 for each group). We
      quantitated villous surface annexin-V in cultured placental villi that were
      incubated with antiphospholipid antibodies immunoglobulin G compared with normal
      immunoglobulin G and measured annexin-V levels by enzyme-linked immunosorbent
      assay in conditioned media and in the villi. RESULTS: The mean villous surface
      annexin-V of the group with antiphospholipid antibodies was 26.2% +/- 17% (SD)
      versus 93.9% +/- 5.7% in the normal control group (p < 0.0001). Villi from
      patients undergoing elective abortions and with pregnancy losses that were not
      attributed to antiphospholipid antibodies also showed higher mean villous surface
      annexin-V levels (86.9% +/- 10.6% and 83.5% +/- 11.3%, respectively, p < 0.0001).
      Organ culture of normal placental villi with affinity-purified immunoglobulin G
      from patients with antiphospholipid antibodies showed a dose-dependent decrease
      of villous surface annexin-V over a concentration range of 1.5 micrograms/ml to
      1.5 mg/ml. Annexin-V concentrations in conditioned media were significantly lower
      in the presence of antiphospholipid antibodies immunoglobulin G compared with
      normal immunoglobulin G (49.4 +/- 8.9 ng/gm wet weight vs 57.2 +/- 11.5 ng/gm,
      respectively, p < 0.05). In contrast, the mean level of annexin-V in placental
      villi incubated with antiphospholipid antibodies immunoglobulin G was greater
      than in villi incubated with normal immunoglobulin G, 1328 +/- 130 ng/gm wet
      weight versus 1183 +/- 165 ng/gm (p < 0.02). CONCLUSIONS: Patients with
      antiphospholipid antibodies and a history of previous pregnancy losses have a
      significant reduction in annexin-V immunostaining on placental villous surfaces,
      and antiphospholipid antibodies immunoglobulin G can directly decrease levels of
      villous surface annexin-V on cultured placental villi. Assays of annexin-V in the
      conditioned media and cell pellets of cultured placental villi suggest that the
      mechanism for antiphospholipid antibodies-mediated reduced annexin-V surface
      staining is an inhibition of annexin-V transport to the villous surface rather
      than displacement by antiphospholipid antibodies from the surface. This
      antiphospholipid antibodies-induced deficiency of placental surface annexin-V may
      contribute to the placental thrombosis observed in these patients.

PMID- 7802070
TI  - Burch colposuspension versus modified Marshall-Marchetti-Krantz urethropexy for
      primary genuine stress urinary incontinence: a prospective, randomized clinical
      trial.
AB  - OBJECTIVE: Our purpose was to compare the effects of the Burch colposuspension
      with those of the modified Marshall-Marchetti-Krantz urethropexy. STUDY DESIGN:
      Eighty women underwent the two types of operation. A full urodynamic
      investigation was repeated 6 months after surgery. RESULTS: Clinical follow-up
      continued for 2 to 7 years. Differences in subjective and objective cure rates
      were not statistically significant (respectively, 92% and 80% for the Burch
      colposuspension and 85 and 65% for the modified Marshall-Marchetti-Krantz
      urethropexy). The latter induced a longer hospital stay (7.4 vs 6.3 days, p =
      0.001), a later resumption of spontaneous voiding (13.8 vs 8.5 days, p = 0.002),
      and was associated with considerable complications (one case of blood replacement
      for retropubic hematoma, one case of severe voiding difficulty, one case of
      further treatment for stress incontinence, and three cases of symptomatic de novo
      detrusor instability). CONCLUSION: For its high cure rate, short time to
      resumption of spontaneous voiding, short hospital stay, and low associated
      morbidity, the Burch colposuspension should remain the procedure of choice for
      stress incontinence.

PMID- 7802071
TI  - An estrogen receptor genetic polymorphism and the risk of primary and secondary
      recurrent spontaneous abortion.
AB  - OBJECTIVE: A case-control study was undertaken to assess the association between
      an estrogen receptor gene variant and the risk of recurrent spontaneous
      abortions. STUDY DESIGN: The frequency of the estrogen receptor gene variant in
      blood lymphocyte deoxyribonucleic acid and other selected maternal
      characteristics was compared among 60 primary recurrent aborters, 61 secondary
      recurrent aborters, and 43 women who had had at least two live births but no
      spontaneous abortions. RESULTS: No association was evident between the estrogen
      receptor gene variant and the risk of either primary or secondary recurrent
      abortion. There were data suggesting that primary recurrent aborters in
      particular were more likely to report a family history of recurrent abortion and
      a family history of breast cancer. CONCLUSIONS: These findings indicate that the
      estrogen receptor polymorphism is not a genetic marker for recurrent spontaneous
      abortions. Therefore, as suggested by previous investigations, this polymorphism
      appears to be a marker for breast cancer risk only among the subgroups who have
      had a history of repeated abortions.

PMID- 7802072
TI  - Single injection of methotrexate for treatment of ectopic pregnancies.
AB  - OBJECTIVE: Our purpose was to evaluate the efficacy of single-dose methotrexate
      as a treatment option for ectopic pregnancies. STUDY DESIGN: Patients were
      recruited from a tertiary teaching hospital setting. They had (1) a gestational
      sac < 3.5 cm, (2) no fetal cardiac activity, and (3) no significant pelvic pain
      or signs consistent with hemoperitoneum. Patients excluded were those who did not
      desire future fertility or who had evidence of renal or liver disease. Sixty-one
      patients meeting these criteria were selected and treated with a single
      intramuscular injection of methotrexate at a dosage of 50 mg/m2. RESULTS: Of the
      61 patients treated, 16 required a second injection and nine required surgical
      intervention. Fifty-two (85%) were successfully treated as outpatients with
      methotrexate alone. CONCLUSION: Nonsurgical treatment of ectopic pregnancies with
      single-dose methotrexate is an option for some patients, but more studies are
      needed to establish the safety, efficacy, and effect on fertility.

PMID- 7802073
TI  - Antiendotoxin antibody is protective against tubal damage in an Escherichia coli
      rabbit salpingitis model.
AB  - OBJECTIVE: This study was designed to determine whether pretreatment with an
      endotoxin antibody reduces tubal damage and tumor necrosis factor-alpha
      production in an Escherichia coli rabbit salpingitis model. STUDY DESIGN: Twenty
      New Zealand White rabbits underwent laparotomy with direct inoculation of
      Escherichia coli into the fallopian tube. The animals were given either antibody
      and antibiotic, antibiotic alone, or no treatment. At 7 days the degree of tubal
      damage was measured by gross observation, light microscopy, and electron
      microscopy. Serum tumor necrosis factor-alpha levels were also assayed at 0, 2,
      4, and 36 hours. RESULTS: Animals pretreated with antiendotoxin antibody
      demonstrated significantly less damage on the basis of gross observation and
      electron microscopy compared with both antibiotic alone and untreated animals.
      Tumor necrosis factor-alpha levels were also significantly reduced at 2 and 4
      hours in the antibody-treated group. CONCLUSIONS: Endotoxin plays a direct role
      in tubal damage in this Escherichia coli salpingitis model, and damage can be
      blocked, in part, by pretreatment with antiendotoxin antibody. Tumor necrosis
      factor-alpha appears to play a significant role in mediating tubal damage
      resulting from endotoxin.

PMID- 7802074
TI  - Tuberculous infertility and in vitro fertilization.
AB  - OBJECTIVES: Our purpose was to assess the outcome of in vitro fertilization and
      embryo transfer in tuberculous infertility and to study the factors associated
      with success or failure of treatment. STUDY DESIGN: Ten patients with tuberculous
      infertility underwent 22 cycles of in vitro fertilization and 9 cryopreserved
      thawed embryo transfers at Bourn Hall Clinic. All patients underwent endometrial
      assessment by ultrasonography. Four patients had preliminary hysteroscopy,
      endometrial biopsy, and Doppler uterine blood flow studies. RESULTS: Six clinical
      pregnancies resulted in three live births in three patients and one current
      pregnancy in a fourth patient. There was one ectopic pregnancy and one twin
      pregnancy that aborted spontaneously at 14 weeks. The patients who had trophic
      endometrium achieved pregnancy at a rate of 42.9% (six of 14) (per embryo
      transfer) compared with 0% (none of 14) if the endometrium was atrophic.
      CONCLUSION: In vitro fertilization and embryo transfer offers the only realistic
      treatment for tuberculous infertility. Preliminary assessment of the endometrium
      is helpful in assessing prognoses in these cases.

PMID- 7802075
TI  - Danazol: prolonged suppression of gonadotropins after subcutaneous administration
      in the castrate male rat.
AB  - OBJECTIVE: Our purpose was to compare oral versus subcutaneous administration of
      danazol for its effect on elevated serum luteinizing hormone and follicle
      stimulating hormone levels in castrated male rats. STUDY DESIGN: A single dose of
      danazol, either 100 or 400 mg/kg, was administered by gastric intubation or
      injected subcutaneously. Jugular venipuncture blood samples were taken at 0, 3,
      24, and 48 hours and at 7, 10, 15, and 25 days, and serum levels of luteinizing
      hormone and follicle-stimulating hormone were determined by radioimmunoassay.
      RESULTS: Gonadotropin levels returned to control values 96 hours after oral
      administration, whereas 400 mg/kg of danazol administered subcutaneously resulted
      in suppression of gonadotropins for 25 days. CONCLUSIONS: Subcutaneous
      administration of danazol results in an unexpectedly prolonged suppression of
      serum gonadotropins compared with the same dose administered orally. A change
      from oral administration to a prolonged-release subcutaneous preparation of
      danazol may enhance the use of this drug in clinical situations and may lessen
      undesirable side effects.

PMID- 7802077
TI  - The accuracy of prenatal ultrasonography in detecting congenital anomalies.
AB  - OBJECTIVES: The purpose of this study was to evaluate the accuracy of prenatal
      ultrasonography in detecting congenital anomalies. STUDY DESIGN: We studied all
      singleton births or fetal deaths with one or more congenital defects delivered
      during the study period who had had one or more ultrasonographic examinations
      performed at or after 16 weeks' gestation and a random sample of defect-free
      newborns similarly examined by ultrasonography. Congenital anomalies reported on
      either the infants' postdelivery medical record or the fetal autopsy report were
      our standard. Prenatal ultrasonographic findings reported during gestation and
      therefore "blind" to the postdelivery outcome were then compared with the
      standard. RESULTS: The overall sensitivity of ultrasonography in detecting
      defects was 53%. The overall specificity was 99%. Ultrasonography proved to be
      highly sensitive (89%) for prevalent lethal malformations. However, serious
      cardiac defects, microcephalus, and many musculoskeletal deformities were missed
      by ultrasonography. CONCLUSION: Ultrasonography is sensitive in detecting many
      lethal malformations. However, a negative prenatal ultrasonographic examination
      does not provide absolute assurance that a fetus is defect free.

PMID- 7802076
TI  - Amnioinfusion and the intrauterine prevention of meconium aspiration.
AB  - OBJECTIVE: We evaluated the published literature on the effectiveness of
      amnioinfusion in reducing meconium below the vocal cords and meconium aspiration
      syndrome among infants born to women presenting with more than trace meconium
      stained fluid. STUDY DESIGN: A literature search was conducted to evaluate
      clinical trials of amnioinfusion and meconium aspiration. Trials meeting certain
      basic design criteria (n = 5), which included a prospective study design and
      blinded assessment of newborn outcome, were selected for statistical analyses
      estimating the average effect's size and direction. In total, 247 women with
      meconium-stained fluid receiving amnioinfusion and 260 women with meconium
      stained fluid not receiving amnioinfusion were represented by these trials.
      RESULTS: Infants born to women with meconium-stained fluid receiving
      amnioinfusion were less likely to have meconium below the vocal cords (odds ratio
      0.13, 95% confidence interval 0.08 to 0.20) and were less likely to have meconium
      aspiration syndrome (odds ratio 0.20, 95% confidence interval 0.08 to 0.48) than
      were infants born to women with meconium-stained fluid not receiving
      amnioinfusion. DISCUSSION: Amnioinfusion appears to be an effective intrauterine
      intervention for the prevention of meconium aspiration. Clinicians should
      consider implementing amnioinfusion in women presenting with thick meconium to
      prevent intrapartal meconium aspiration in newborns.

PMID- 7802078
TI  - Amniotic fluid prostanoid concentrations increase early during the course of
      spontaneous labor at term.
AB  - OBJECTIVE: The purpose of this study was to determine whether amniotic fluid
      concentrations of prostanoids increase during spontaneous labor at term. STUDY
      DESIGN: Amniotic fluid was retrieved transabdominally from 168 patients in
      spontaneous labor and from 82 patients not in labor. Prostaglandin E2,
      prostaglandin F2 alpha, 13, 14-dihydro-15-keto-prostaglandin F2 alpha,
      thromboxane B2, and 6-keto-prostaglandin F1 alpha concentrations were measured
      with sensitive and specific radioimmunoassays previously validated for amniotic
      fluid. Statistical analysis was conducted with Kruskal-Wallis analysis of
      variance, followed by Dunn's test for multiple comparisons. RESULTS: (1) Amniotic
      fluid concentrations of all prostanoids were significantly higher in patients in
      early labor (cervical dilatation of < or = 3 cm) than in patients not in labor.
      (2) The magnitude of the increase in amniotic fluid prostanoid concentrations
      during early labor was significantly greater for prostaglandin F2 alpha and 13,14
      dihydro-15-keto-prostaglandin F2 alpha than for prostaglandin E2, thromboxane B2,
      and 6-keto-prostaglandin F1 alpha. (3) Patients in the active phase of labor with
      cervical dilatations between 4 and 7 cm did not have higher prostanoid
      concentrations than those in early labor (cervical dilatation of < or = 3 cm).
      (4) A significant increase in amniotic fluid concentrations of prostaglandin F2
      alpha and 13,14-dihydro-15-keto-prostaglandin F2 alpha was found in patients with
      advanced cervical dilatation (8 to 10 cm) in comparison with those in early labor
      (< 3 cm). CONCLUSION: Amniotic fluid prostanoid concentrations increase early
      during the course of spontaneous labor at term.

PMID- 7802079
TI  - Comparing clinician-applied loads for routine, difficult, and shoulder dystocia
      deliveries.
AB  - OBJECTIVE: Our goal was to examine and compare clinician-applied loads during
      simulated vaginal delivery. STUDY DESIGN: We developed a birthing model and a
      microcomputer data acquisition system and used them to measure clinician-applied
      extraction forces, moment, and rates for three perceived categories of delivery.
      In 39 experiments, clinicians simulated delivery of the fetal shoulders during
      vaginal delivery for routine, difficult, and shoulder dystocia deliveries.
      RESULTS: Clinicians averaged 84 N combined force and 473 N-cm neck-bending moment
      for routine deliveries, 122 N and 697 N-cm for difficult deliveries, and 163 N
      and 700 N-cm for shoulder dystocia deliveries (p < 0.002). No force or moment
      parameter was associated with clinician gender or experience. Force levels
      exceeding 100 N are reached for many clinicians (74% and 82%) for difficult and
      shoulder dystocia deliveries and for some clinicians (31%) for routine deliveries
      (p < 0.0001). CONCLUSION: We conclude that simulating shoulder dystocia in the
      laboratory may be useful in measuring extraction forces and neck-bending moment
      and that birthing models can be used to train clinicians in force, moment, and
      rate perception.

PMID- 7802080
TI  - Effect of oxytocin antagonists on the activation of human myometrium in vitro:
      atosiban prevents oxytocin-induced desensitization.
AB  - OBJECTIVE: Our purpose was to investigate whether the sensitivity of myometrial
      cells to oxytocin is affected by prolonged exposure to oxytocin antagonists.
      STUDY DESIGN: Tissue slices or cultured myometrial cells were exposed to peptides
      in vitro. Myometrial activation was studied by measuring the formation of
      inositol phosphates and the changes in intracellular calcium. Oxytocin binding
      was measured by saturation analysis. RESULTS: Atosiban and related peptides
      inhibited oxytocin-induced myometrial activation as pure antagonists (inhibition
      constant 10 nmol/L) but had no effect on prostaglandin E2-induced activation.
      Long-term (> or = 24 hours) exposure to atosiban had no residual effect on
      oxytocin sensitivity. However, long-term exposure to oxytocin resulted in
      homologous desensitization and loss of oxytocin receptors. Oxytocin-induced
      desensitization was prevented by coincubation with atosiban. CONCLUSIONS:
      Atosiban is a pure oxytocin antagonist and has a specific, reversible effect on
      myometrial cells in vitro. Its potential use for the management or even
      prevention of idiopathic preterm labor or to reverse uterine hypertony during
      oxytocin-induced labor should be tested in controlled clinical trials.

PMID- 7802081
TI  - Receptors for and myometrial responses to oxytocin and vasopressin in preterm and
      term human pregnancy: effects of the oxytocin antagonist atosiban.
AB  - OBJECTIVE: Our purpose was to study myometrial oxytocin and type V1 vasopressin
      receptors, the in vitro contractile effects of these hormones, and the influence
      of an oxytocin antagonist. STUDY DESIGN: Women delivered by cesarean section
      preterm (n = 51) and at term (n = 71), with and without labor contractions, gave
      myometrium for the estimation of oxytocin and V1 vasopressin receptors. The in
      vitro myometrial effects of the peptides and the influence on these of the
      competitive oxytocin receptor blocking agent 1-deamino-2-D-Tyr(OEt)-4-Thr-8-Orn
      oxytocin were also tested. RESULTS: The median concentration of oxytocin
      receptors was 116 fmol/mg protein (range 15 to 372 fmol/mg protein) in patients
      delivered preterm not in labor, 134 fmol/mg protein (27 to 1421 fmol/mg protein)
      in the beginning of labor, and 46 fmol/mg protein (9 to 140 fmol/mg protein) in
      advanced labor. At term the corresponding concentrations were 172 (25 to 629),
      223 (24 to 414), and 70 (21 to 92) fmol/mg protein. The concentration of V1
      vasopressin receptors also decreased in advanced labor. In advanced labor after
      oxytocin infusion a reduction in the concentration of the receptor for this
      hormone was observed, which appeared to be related to the duration and dose of
      treatment. Oxytocin receptors did not vary between women with different
      indications for cesarean section. The oxytocin effects in vitro and the degree of
      inhibition by the antagonist of oxytocin responses correlated with the
      concentration of oxytocin receptors but not with that of V1 vasopressin
      receptors. No correlation was seen between the response to vasopressin and
      concentrations of oxytocin or V1 vasopressin receptors. CONCLUSIONS: The effect
      of oxytocin on the myometrium in pregnancy is mediated by an oxytocin receptor,
      whereas vasopressin acts on both oxytocin and vasopressin receptors. The
      initiation of labor both preterm and at term may be primarily related to
      increased release of oxytocin, which is locally produced in the uterus and not
      detectable in the plasma, but oxytocin and vasopressin receptors may play a role
      in the regulation of labor. The analog 1-deamino-2-D-Tyr(OEt)-4-Thr-8-Orn
      oxytocin, which blocks both the oxytocin and the V1 vasopressin receptor, should
      inhibit labor both preterm and at term, the former confirming results of recent
      clinical studies in Sweden and the United States.

PMID- 7802082
TI  - Plasma levels of atrial natriuretic peptide in normal and hypertensive
      pregnancies: a meta-analysis.
AB  - OBJECTIVE: Our goals were (1) to use meta-analysis to determine whether pregnancy
      and the puerperium are accompanied by alterations in plasma atrial natriuretic
      peptide levels when compared with the nonpregnant state and (2) to evaluate the
      additional effects of hypertensive disease during pregnancy on plasma atrial
      natriuretic peptide levels. STUDY DESIGN: Articles measuring atrial natriuretic
      peptide levels during pregnancy were reviewed. Data from articles meeting
      inclusion criteria were abstracted, and a meta-analysis was performed with the
      use of the maximum likelihood methods of Jennrich and Schluchter (Biometrics
      1986;42:805-20). RESULTS: The mean atrial natriuretic peptide level in
      nonpregnant control subjects was 28.7 pg/ml (95% confidence interval 22.5 to
      36.7). The mean plasma atrial natriuretic peptide level rose 41% to 40.5 pg/ml
      (95% confidence interval 31.7 to 51.8) in the third trimester (p < 0.0001). It
      was 71.1 pg/ml (95% confidence interval 51.2 to 98.7) or 148% greater than the
      mean nonpregnant level during the first week post partum (p < 0.0001). Compared
      with levels in pregnant control subjects, plasma atrial natriuretic peptide
      levels increased 52% to 52.1 pg/ml (95% confidence interval 32.9 to 82.5) in
      women with gestational hypertension (p < 0.005) and 130% to 78.8 pg/ml (95%
      confidence interval 52.3 to 118.8) in women with preeclampsia (p < 0.0001).
      Chronic hypertension did not significantly alter atrial natriuretic peptide
      levels. CONCLUSIONS: The 41% increase in atrial natriuretic peptide levels in the
      third trimester suggests that atrial stretch receptors sense the expanded blood
      volume as normal to moderately increased. The rise in atrial natriuretic peptide
      during the first week post partum is consistent with known hemodynamic changes
      and suggests that atrial natriuretic peptide may be involved in the postpartum
      diuresis. The marked increase in plasma atrial natriuretic peptide levels
      observed in preeclampsia is not likely to result from elevated arterial pressures
      alone but may reflect underlying factors unique to this disease process.

PMID- 7802083
TI  - Dexamethasone partially protects the myometrium against beta-adrenergic agonist
      induced desensitization in vivo in the rat.
AB  - OBJECTIVE: Our purpose was to determine the ability of dexamethasone to prevent
      the onset of myometrial desensitization to beta-adrenergic agonists in vivo.
      STUDY DESIGN: On day 5 post partum chronically catheterized rats were randomized
      to receive either dexamethasone or corn oil (vehicle), followed 12 hours later by
      a continuous infusion of either isoproterenol or saline solution (vehicle).
      Uterine contractions were monitored throughout. We measured myometrial
      glucocorticoid receptor levels in chronically catheterized and sham-operated rats
      and beta 2-adrenergic receptor densities in the experimental rats before and
      during the infusions. RESULTS: Surgery did not lead to any decrease in
      glucocorticoid receptor number. Dexamethasone significantly increased the
      duration of myometrial responsiveness to isoproterenol compared with vehicle
      pretreated rats, although agonist-induced down-regulation of beta-adrenergic
      receptor number was not prevented. CONCLUSION: Dexamethasone partially protects
      the rat myometrium from desensitization induced by the continuous infusion of
      beta-adrenergic agonists through mechanisms independent of the beta 2-receptor.

PMID- 7802084
TI  - An experimental model for intraamniotic infection and preterm labor in rhesus
      monkeys.
AB  - OBJECTIVE: Our purpose was to describe the temporal and quantitative relationship
      between intraamniotic infection and preterm labor in a nonhuman primate model.
      STUDY DESIGN: On day 130 of gestation (term 167 days) four chronically
      instrumented rhesus monkeys (Macaca mulatta) were infected with an intraamniotic
      inoculation of 10(6) colony-forming units of group B streptococci. Four
      additional noninfected monkeys were followed up to spontaneous parturition as
      controls. Amniotic fluid was serially sampled in all monkeys both before and
      after inoculation for bacterial growth, tumor necrosis factor-alpha, interleukin
      1 beta, interleukin-6, prostaglandin E2, and prostaglandin F2 alpha, and uterine
      activity was continuously recorded. RESULTS: Increases in uterine contractility
      occurred 28 hours (range 14 to 40 hours) after inoculation and were preceded by
      increases in amniotic fluid cytokines and prostaglandins. Intraamniotic
      concentrations of tumor necrosis factor-alpha, interleukin-6, and interleukin-1
      beta all rose dramatically 9, 15, and 18 hours after infection and 10 to 20 hours
      before increases in uterine contractility. In spontaneous parturition only
      interleukin-6 concentrations rose moderately (from 0.1 to 1.2 ng/ml). Increases
      in prostaglandin E2 and prostaglandin F2 alpha paralleled those of the cytokines.
      Peak prostaglandin concentrations in intraamniotic infection exceeded by
      severalfold concentrations seen in spontaneous parturition (16,046 pg/ml vs 2765
      pg/ml for prostaglandin E2, p < 0.05; and 5547 pg/ml vs 708 pg/ml for
      prostaglandin F2 alpha, p < 0.05). In spite of intraamniotic none of the monkeys
      were febrile or had peripheral leukocytosis at the onset of labor. CONCLUSION: In
      the rhesus monkey, after intraamniotic infection, there is a predictable and
      sequential increase in amniotic fluid tumor necrosis factor-alpha, interleukin-1
      beta, and interleukin-6, followed by increases in prostaglandin E2 and
      prostaglandin F2 alpha. These increases all occur before an increase in uterine
      contractility and before clinical signs of infection. Our data provide evidence
      for a cause-and-effect relationship between intraamniotic infection and preterm
      labor and support the utility of measuring interleukin-6 or other cytokines in
      the diagnosis of intraamniotic infection.

PMID- 7802085
TI  - Induction of interleukin-1 receptor antagonist in rhesus monkeys after
      intraamniotic infection with group B streptococci or interleukin-1 infusion.
AB  - OBJECTIVE: Interleukin-1 receptor antagonist is a natural inhibitor of
      interleukin-1, a cytokine implicated in the initiation of preterm labor after
      intraamniotic infection. The effects of intraamniotic infection and interleukin-1
      infusion on the appearance of interleukin-1 receptor antagonist in amniotic fluid
      and fetal and maternal plasma were assessed with a monkey model. STUDY DESIGN: On
      day 130 of pregnancy four chronically catheterized rhesus macaques received
      intraamniotic inoculations of group B streptococci, three monkeys received
      intraamniotic infusions of recombinant human interleukin-1 beta, and three
      monkeys received buffered saline solution infusions. At timed intervals samples
      of amniotic fluid, fetal plasma, and maternal plasma were assayed for interleukin
      1 beta and interleukin-1 receptor antagonist by immunoassays. Uterine activity
      was continuously monitored by intraamniotic pressure catheters and by
      electromyographic activity. RESULTS: Interleukin-1 receptor antagonist, but not
      interleukin-1 beta, was present in the amniotic fluids of all monkeys before
      intervention. Infection induced the appearance of interleukin-1 beta and an
      increase in interleukin-1 receptor antagonist in the amniotic fluid. Interleukin
      1 beta infusion resulted in a similar increase in the intraamniotic concentration
      of interleukin-1 receptor antagonist. Both infection and interleukin-1 beta
      infusion were followed by the transient appearance of interleukin-1 receptor
      antagonist in the plasma of all fetuses. The subsequent decrease in plasma levels
      was paralleled by increased amniotic fluid levels of interleukin-1 receptor
      antagonist. Interleukin-1 beta and interleukin-1 receptor antagonist were not
      detected in maternal plasma. Both infection and interleukin-1 infusion induced
      preterm labor in all treated animals. CONCLUSIONS: Interleukin-1 receptor
      antagonist is a normal component of monkey amniotic fluid. Intraamniotic
      infection or the appearance of interleukin-1 beta in the amniotic fluid results
      in increased production of interleukin-1 receptor antagonist. Under physiologic
      conditions interleukin-1 receptor antagonist in amniotic fluid may inhibit
      interleukin-1-induced preterm labor.

PMID- 7802086
TI  - Hysteroscopic views and endometrial behavior.

PMID- 7802087
TI  - Adverse tissue reaction after surgical management of stress incontinence with
      expanded polytetrafluoroethylene.

PMID- 7802088
TI  - Group B streptococcal prophylaxis.

PMID- 7802089
TI  - More on the importance of transvaginal ultrasonography follow-up in the treatment
      of persistent hydatidiform mole.

PMID- 7802090
TI  - Transvaginal visualization of the corpus callosum.

PMID- 7802091
TI  - Paranthropus boisei: an example of evolutionary stasis?
AB  - Of the presently recognised early hominid species, Paranthropus boisei is one of
      the better known from the fossil record and arguably the most distinctive; the
      latter interpretation rests on the numbers of apparently derived characters it
      incorporates. The species as traditionally diagnosed is distributed across
      approximately one million years and is presently confined to samples from East
      African sites. The hypodigm has been examined for evidence of intraspecific
      phyletic evolution, with particular emphasis on the areas best represented in the
      fossil record, namely the teeth and mandible. The results of this examination of
      55 mandibular and dental variables which uses the gamma test statistic for the
      detection of trend, and nonparametric spline regression (Loess regression) for
      investigating pattern and rate of temporal change, show that within Paranthropus
      boisei sensu stricto most evidence of temporally related morphological trends
      relates to the morphology of the P4 crown. There is little or no evidence of any
      tendency to increase in overall size through time. Fossils from the Omo Shungura
      Formation and West Turkana which have been recovered from a time period earlier
      than the P. boisei sensu stricto hypodigm resemble the latter taxon in some
      features, but differ from it in aspects of cranial morphology. There is
      insufficient fossil evidence of the earlier taxon to tell whether it changes
      through time, but when trends of 47 mandibular and dental variables are assessed
      across the combined East African "robust" australopithecine sample, there is
      evidence for a relatively abrupt change around 2.2-2.3 Myr in approximately 25%
      of the dental and mandibular remains. Some of these changes correspond with the
      temporal trends within P. boisei sensu stricto, but others, such as mandible
      height, do not. If the earlier material is ancestral to P. boisei sensu stricto,
      evidence from the teeth and jaws is consistent with a punctuated origin for the
      latter taxon.

PMID- 7802092
TI  - Genetic variation in North Africa and Eurasia: neolithic demic diffusion vs.
      Paleolithic colonisation.
AB  - The hypothesis that both genetic and linguistic similarities among Eurasian and
      North African populations are due to demic diffusion of neolithic farmers is
      tested against a wide database of allele frequencies. Demic diffusion of farming
      and languages from the Near East should have determined clines in areas defined
      by linguistic criteria; the alternative hypothesis of cultural transmission does
      not predict clines. Spatial autocorrelation analysis shows significant gradients
      in three of the four linguistic families supposedly affected by neolithic demic
      diffusion; the Afroasiatic family is the exception. Many such gradients are not
      observed when populations are jointly analyzed, regardless of linguistic
      classification. This is incompatible with the hypothesis that major cultural
      transformations in Eurasia (diffusion of related languages and spread of
      agriculture) took place without major demographic changes. The model of demic
      diffusion seems therefore to provide a mechanism explaining coevolution of
      linguistic and biological traits in much of the Old World. Archaeological,
      linguistic, and genetic evidence agree in suggesting a multidirectional process
      of gene flow from the Near East in the neolithic. However, the possibility should
      be envisaged that some allele frequency patterns can predate the neolithic and
      depend on the initial spread of Homo sapiens sapiens from Africa into Eurasia.

PMID- 7802093
TI  - Altitude, language, and class I HLA allele frequencies in Papua New Guinea.
AB  - Class I HLA gene frequencies show considerable variation over short geographical
      distances in Papua New Guinea. Hypothesis to account for this invoke natural
      selection, population structure, the pattern of population movement, or past
      demographic changes. To determine the role of the various factors in shaping this
      distribution, we have studied correlations between HLA-based genetic distances,
      geographical distances, altitude, and linguistic differences in Papua New Guinea.
      Linguistic differences at the family or stock level within the Trans-New Guinea
      Phylum generally correspond to genetic differences. However, on the basis of
      their HLA gene frequencies, speakers of Austronesian (AN) languages do not form a
      distinct group of populations. Linguistic variation and spatial autocorrelation
      do not fully account for the altitudinal cline differences noted in gene
      frequencies, particularly at the HLA-A locus. We propose that the distribution of
      HLA gene frequencies in Papua New Guinea is partially under the control of
      selection operating differentially along the altitude gradient.

PMID- 7802094
TI  - Inflammatory lesions of ribs: an analysis of the Terry Collection.
AB  - The aim of this paper is to consider the diagnostic criteria for tuberculosis in
      ancient populations. It investigates the frequency of periosteal new bone
      formation on the visceral surfaces of ribs from 1718 individuals from the Terry
      Collection, Smithsonian Institution, Washington D.C. and attempts to determine
      the aetiological factors producing these lesions. Numbers of individuals with
      lesions according to cause of death were recorded and the patterning of lesions
      compared between people who had died from tuberculosis and those whose cause of
      death was unrelated to a pulmonary disease. Rib lesions were more common in
      individuals dying from tuberculosis (61.6% or 157 of 255) than in individuals
      dying from other causes (15.2% or 165 of 1086). It is suggested that tuberculosis
      at a peripheral lung focus may disseminate directly through the pleura to the
      visceral surfaces of the ribs, or that pulmonary tuberculosis may be the cause of
      empyema of the pleural cavity and that this, per se, may initiate inflammatory
      change on the visceral surfaces of ribs. The nonrecognition or description of
      these often very subtle proliferative lesions on ribs by radiological examination
      of tuberculous victims is significant in the discussion of bone changes in
      tuberculosis. The possibility that individuals with no recorded history of
      tuberculosis at death actually suffered from the disease was considered in light
      of the frequency of rib lesions and noncorrelation with a tuberculous cause of
      death. Differential diagnoses are discussed including the possibility that the
      lesions represent a general non-specific indicator of stress.

PMID- 7802095
TI  - Early ontogeny of the human femoral bicondylar angle.
AB  - The presence of a femoral bicondylar angle consistently and significantly greater
      than 0 degrees has been a hallmark of hominid bipedality, but its pattern of
      development has not been documented. We have therefore compiled cross-sectional
      data on the development of the articular bicondylar angle for a clinical sample
      of modern humans and of the metaphyseal bicondylar angle for two Recent human
      skeletal samples, one predominantly European in origin and the other Amerindian.
      All three samples exhibit a pattern of a bicondylar angle of 0 degrees at birth
      and then a steady average increase in the angle from late in the first year
      postnatal, through infancy; and into the juvenile years. The two skeletal samples
      reach low adult values by approximately 4 years postnatal, whereas the clinical
      sample with a lowered activity level appears to attain consistent adult values
      slightly later (approximately 6 years postnatal). In addition, two modern human
      individuals, one nonambulatory and the other minimally ambulatory, show no and
      little development, respectively, of a bicondylar angle. These data, in
      conjunction with clinical and experimental observations on the potential and form
      of angular changes during epiphyseal growth, establish a high degree of potential
      for plasticity in the development of the human bicondylar angle and the direct
      association of a bipedal locomotion and (especially) posture with the
      developmental emergence of a human femoral bicondylar angle.

PMID- 7802096
TI  - Patterns of ingestive behavior and anterior tooth use differences in sympatric
      anthropoid primates.
AB  - Little research has been directed towards the examination of ingestive behaviors
      in wild primates. This paper describes a naturalistic study of anterior tooth use
      in four sympatric anthropoid species: Hylobates lar, Macaca fascicularis, Pongo
      pygmaeus, and Presbytis thomasi. Instantaneous group scan data were collected
      during nearly 1,800 hours of observation between August 1990 and July 1991 at the
      Ketambe Research Station in the Gunung Leuser National Park, Sumatra, Indonesia.
      Ingestive behaviors are documented for specific food items and compared among the
      primate taxa. Results indicate significant differences among the species in
      preferred methods of food ingestion. These differences are related in part to
      dietary differences, and in part to other aspects of each primate's biology and
      ecology.

PMID- 7802097
TI  - Enamel microstructure in Lemuridae (Mammalia, Primates): assessment of
      variability.
AB  - This study describes the molar enamel microstructure of seven lemurid primates:
      Hapalemur griseus, Varecia variegata, Lemur catta, Lemur macaco, Lemur fulvus
      rufus, Lemur fulvus fulvus, and Lemur fulvus albifrons. Contrary to earlier
      accounts, which reported little or no prism decussation in lemurid enamel, both
      Lemur and Varecia molars contain a prominent inner layer of decussating prisms
      (Hunter-Schreger bands), in addition to an outer radial prism layer, and a thin,
      nonprismatic enamel surface layer. In contrast, Hapalemur enamel consists
      entirely of radial and, near the surface, nonprismatic enamel. In addition, for
      all species, prism packing patterns differ according to depth from the tooth
      surface, and for all species but Varecia (which also has the thinnest enamel of
      any lemurid), average prism area increases from the enamel-dentine junction to
      the surface; this may be a developmental solution to the problem of accommodating
      a larger outer surface area with enamel deposited from a fixed number of cells.
      Finally, contradicting some previous reports, Pattern 1 prisms predominate only
      in the most superficial prismatic enamel. In the deeper enamel, prism cross
      sections include both closed (Pattern 1) and arc-shaped (Pattern 2 or, most
      commonly, Pattern 3). This sequence of depth-related pattern change is repeated
      in all taxa. It should also be emphasized that all taxa can exhibit all three
      prism patterns in their mature enamel. The high degree of quantitative and
      qualitative variation in prism size, shape, and packing suggests that these
      features should be used cautiously in phylogenetic studies. Hapalemur is
      distinguished from the other lemurids by unique, medially constricted or
      rectangular prism cross-sections at an intermediate depth and the absence of
      prism decussation, but, without further assessment of character polarity, these
      differences do not clarify lemurid phylogenetic relations. Some characters of
      enamel microstructure may represent synapomorphies of Lemuridae, or of clades
      within Lemuridae, but homoplasty is likely to be common. Homoplasy of enamel
      characters may reflect functional constraints.

PMID- 7802098
TI  - Grief: normal and pathological variants.

PMID- 7802099
TI  - Attempted suicide among Vietnam veterans: a model of etiology in a community
      sample.
AB  - OBJECTIVE: Data from the National Vietnam Veterans Readjustment Study, conducted
      from 1986 to 1988, were used to develop an etiological model of attempted suicide
      among a community sample of 1,198 male Vietnam veterans. METHODS: In a three-step
      process, the authors used structural equation modeling to develop a model that
      they refined, cross-validated, and then specified in terms of its replicable
      paths. RESULTS: The final model possesses highly satisfactory fit and parsimony.
      General psychiatric disorders were the sole factors contributing directly to
      attempted suicide. General psychiatric disorders were in part products of both
      nonmilitary and military traumas, most specifically participation in abusive
      violence. Posttraumatic stress disorder (PTSD) and substance abuse were related
      to attempted suicide bivariately but not when considered in conjunction with
      general psychiatric disorders. Among premilitary risk factors, family instability
      contributed to attempted suicide indirectly through its influence on general
      psychiatric disorders. CONCLUSIONS: The etiology of attempted suicide among
      Vietnam veterans remains largely unexplained. A partial explanation is that the
      predominant and direct causes spring from general psychiatric disorders rather
      than from traumatic exposure, PTSD, or substance abuse. Traumatic exposure
      contributes directly to the development of PTSD and general psychiatric disorders
      but only indirectly to making a suicide attempt.

PMID- 7802100
TI  - Sleep events among veterans with combat-related posttraumatic stress disorder.
AB  - OBJECTIVE: Sleep disturbances are important features of posttraumatic stress
      disorder (PTSD); however, the published data characterizing PTSD sleep phenomena
      are limited. The authors report on the phenomenology and physiological correlates
      of symptomatic sleep events in PTSD. METHOD: The study data included survey
      results that addressed sleep symptoms during the past month in combat veterans
      with and without PTSD (N = 58), sleep diary records of awakenings from combat
      veterans with PTSD hospitalized on an inpatient rehabilitation unit (N = 52), and
      overnight polysomnography recordings obtained from 21 medication-free combat
      veterans with PTSD and eight healthy comparison subjects not exposed to combat.
      RESULTS: Recurrent awakenings, threatening dreams, thrashing movements during
      sleep, and awakenings with startle or panic features represented the most
      prevalently reported sleep-related symptoms. Laboratory findings of longer time
      awake, micro-awakenings, and a trend for patients to exhibit body and limb
      movements during sleep are consistent with the subjectively reported symptom
      profile. Prospectively assessed symptomatic awakenings featured startle or panic
      symptoms or anxiety related to threatening dreams. Laboratory findings revealed a
      trend for the symptomatic awakenings (with and without dream recall) to be
      disproportionately preceded by REM sleep, and the two recorded awakenings with
      objective physiological arousal were preceded by REM. CONCLUSIONS: PTSD features
      intrusions into sleep of more highly aroused behaviors and states, which appear
      partially conditioned to REM sleep.

PMID- 7802101
TI  - Arousal, numbing, and intrusion: symptom structure of PTSD following assault.
AB  - OBJECTIVE: This study investigated hypotheses concerning the importance of
      symptoms of numbing in posttraumatic stress disorder (PTSD). METHODS: Symptoms of
      PTSD were assessed in 72 female rape victims and 86 female victims of nonsexual
      assault approximately 3 months after the crimes occurred. A principal-components
      factor analysis of subjects' symptoms was then undertaken. RESULTS: The analysis
      yielded three factors: arousal/avoidance, numbing, and intrusion. These were
      somewhat different from the symptom clusters in DSM-III-R, since effortful
      avoidance and numbing symptoms did not load on the same factor. Numbing symptoms
      appeared to be particularly important in identifying individuals with PTSD.
      CONCLUSIONS: The results imply that there are two patterns of posttrauma
      symptoms, one characterizing PTSD and the second characterizing a phobic
      reaction.

PMID- 7802102
TI  - Fluoxetine and extrapyramidal side effects.
AB  - OBJECTIVE: The authors' goal was to determine whether fluoxetine is associated
      with extrapyramidal side effects. METHOD: They assessed the notifications of
      extrapyramidal manifestations in patients given fluoxetine in the New Zealand
      Intensive Medicines Monitoring Programme, a national system that monitored
      adverse reactions associated with fluoxetine over a 4-year period, and determined
      whether these adverse reactions were causally related to fluoxetine. RESULTS: In
      reports of adverse reactions in 5,555 patients given fluoxetine throughout New
      Zealand, there were 15 notifications of extrapyramidal events probably or
      possibly caused by fluoxetine. Fluoxetine was the only psychotropic agent used
      for seven of the 15 patients; two patients were also taking lithium, four were
      taking neuroleptics, two were taking tricyclic antidepressants, and one was
      taking metoclopramide. CONCLUSIONS: The authors conclude that fluoxetine may be
      associated with extrapyramidal reactions. These may occur with fluoxetine alone
      or fluoxetine may facilitate the reaction in patients receiving psychotropic
      medication or dopamine receptor blocking drugs.

PMID- 7802103
TI  - Basal ganglia phosphorous metabolism in chronic schizophrenia.
AB  - OBJECTIVE: The authors examined whether there are abnormalities in high-energy
      phosphorous metabolism in the basal ganglia of schizophrenic patients. METHOD: In
      vivo 31P magnetic resonance spectroscopic imaging was performed on 18 chronic
      schizophrenic patients and 16 healthy comparison subjects. The percentages of
      total phosphorous signal for phosphomonoesters, inorganic phosphate,
      phosphodiesters, phosphocreatine, and beta-ATP were calculated. RESULTS: The mean
      percentages of beta-ATP signal in the right and left basal ganglia were
      significantly lower for the schizophrenic patients than for the comparison group.
      No other group differences in phosphorous metabolites and no lateral asymmetries
      in the schizophrenic group were noted. CONCLUSIONS: This preliminary study
      provides support for abnormal high-energy phosphorous metabolism in the basal
      ganglia of schizophrenic patients.

PMID- 7802104
TI  - Improvement of some schizophrenic deficit symptoms with low doses of amisulpride.
AB  - OBJECTIVE: The authors assessed the effects on primary negative symptoms of low
      doses of amisulpride, a substituted benzamide neuroleptic with high affinity for
      D2 and D3 dopamine receptors. METHOD: Young, drug-free schizophrenic patients
      with pure negative symptoms participated in a 6-week double-blind trial of
      placebo (N = 10) or low-dose amisulpride (N = 10). They were assessed with the
      Scale for the Assessment of Negative Symptoms. RESULTS: Amisulpride significantly
      improved negative symptoms. Improvement in avolition, attentional impairment, and
      retardation was significantly greater with amisulpride than with placebo.
      CONCLUSIONS: These findings suggest that some primary negative symptoms may be
      directly affected by low doses of benzamide neuroleptics.

PMID- 7802105
TI  - Exclusion of close linkage of the dopamine transporter gene with schizophrenia
      spectrum disorders.
AB  - OBJECTIVE: Involvement of genetic factors in the pathogenesis of schizophrenia
      spectrum disorders has been indicated in twin, adoption, and familial aggregation
      studies; the pivotal role played by the dopamine transporter in dopaminergic
      neurotransmission makes it a candidate gene for these disorders. Detection of
      close linkage between a dopamine transporter marker and schizophrenia spectrum
      disorders would strongly support the existence of causal relationships between
      genetic mutations at the dopamine transporter locus and the disease phenotype.
      METHOD: The authors assessed the linkage between this gene and schizophrenia
      spectrum disorders by using polymorphic dopamine transporter gene markers in 156
      subjects from 16 multiplex pedigrees with schizophrenia as well as
      schizophreniform, schizoaffective, and schizotypal disorders and mood-incongruent
      psychotic depression. RESULTS: Complete (theta = 0.0) linkage to the
      schizophrenia spectrum was excluded under both dominant and recessive models.
      CONCLUSIONS: These results indicate that allelic variants at the dopamine
      transporter locus do not provide major genetic contributions to the etiology of
      schizophrenia and related disorders in these pedigrees.

PMID- 7802107
TI  - Panic disorder in a patient taking oxaprozin.

PMID- 7802106
TI  - Learning and memory in combat veterans with posttraumatic stress disorder.
AB  - OBJECTIVE: The authors investigated a broad range of memory functions for stimuli
      unrelated to trauma to determine whether symptoms such as intrusive memories
      might reflect an underlying cognitive deficit unrelated to the psychological
      content of the traumatic memory in patients with posttraumatic stress disorder
      (PTSD). METHOD: The authors measured the intellectual functioning of 20 male
      combat veterans with PTSD and 12 normal comparison subjects using the WAIS and
      evaluated them for performance on memory using the California Verbal Learning
      Test. RESULTS: Veterans with PTSD showed normal abilities in the functions of
      initial attention, immediate memory, cumulative learning, and active interference
      from previous learning. However, these veterans showed a circumscribed cognitive
      deficit, manifested by the presence of substantial retroactive interference and
      revealed by a significant decrement in retention following exposure to an
      intervening word list. CONCLUSIONS: The data suggest that patients with PTSD may
      have fairly specific deficits in the monitoring and regulation of memory
      information.

PMID- 7802108
TI  - Paroxetine withdrawal syndrome.

PMID- 7802109
TI  - Treatment of organic hallucinosis with carbamazepine.

PMID- 7802110
TI  - Schizophrenia risk for women from in utero exposure to influenza.

PMID- 7802111
TI  - Use of a common language effect size statistic.

PMID- 7802112
TI  - Clozapine's cost effectiveness.

PMID- 7802113
TI  - Clozapine's cost effectiveness.

PMID- 7802114
TI  - Dexamethasone suppression test and depression prognosis.

PMID- 7802115
TI  - Homosexuality and the military.
AB  - OBJECTIVE: Homosexuality has remained a focus of military concern despite
      society's increasing acceptance of homosexual men and women and evidence that
      homosexuals have served and currently serve in the U.S. armed forces. President
      Clinton has stated a determination to end discrimination against homosexuals in
      the military and reverse the exclusionary policy on homosexuals serving in the
      armed forces. The authors review the history of the policy of the U.S. military
      to exclude homosexuals from serving in the armed forces. METHOD: The data for
      this study were drawn from military archives and court cases that have shaped
      U.S. policy excluding homosexuals from serving in the armed forces. The three
      main arguments are addressed: 1) homosexuality is a mental disorder rendering a
      person unstable, 2) homosexual service members are a source of poor morale for
      military units, and 3) homosexual service members are poor security risks.
      RESULTS: Considerable evidence demonstrates that homosexuals in the military pose
      no documented threat to national security and show no evidence of poor work
      performance. CONCLUSIONS: Although issues of morale and fraternization in the
      military remain challenges, no evidence in this review supports the exclusion of
      homosexuals from service in the U.S. armed forces.

PMID- 7802116
TI  - Complicated grief and bereavement-related depression as distinct disorders:
      preliminary empirical validation in elderly bereaved spouses.
AB  - OBJECTIVE: This study sought to determine whether a set of symptoms interpreted
      as complicated grief could be identified and distinguished from bereavement
      related depression and whether the presence of complicated grief would predict
      enduring functional impairments. METHOD: Data were derived from a study group of
      82 recently widowed elderly individuals recruited for an investigation of
      physiological changes in bereaved persons. Baseline data were collected 3-6
      months after the deaths of the subjects' spouses, and follow-up data were
      collected from 56 of the subjects 18 months after the baseline assessments.
      Candidate items for assessing complicated grief came from a variety of scales
      used to evaluate emotional functioning (e.g., the Hamilton Depression Rating
      Scale, the Brief Symptom Inventory). The outcome variables measured were global
      functioning, medical illness burden, sleep, mood, self-esteem, and anxiety.
      RESULTS: A principal-components analysis conducted on intake data (N = 82)
      revealed a complicated grief factor and a bereavement-depression factor. Seven
      symptoms constituted complicated grief: searching, yearning, preoccupation with
      thoughts of the deceased, crying, disbelief regarding the death, feeling stunned
      by the death, and lack of acceptance of the death. Baseline complicated grief
      scores were significantly associated with impairments in global functioning,
      mood, sleep, and self-esteem in the 56 subjects available for follow-up.
      CONCLUSIONS: The symptoms of complicated grief may be distinct from depressive
      symptoms and appear to be associated with enduring functional impairments. The
      symptoms of complicated grief, therefore, appear to define a unique disorder
      deserving of specialized treatment.

PMID- 7802117
TI  - Atypical depression: clinical aspects and noradrenergic function.
AB  - OBJECTIVE: The authors assessed the frequency of atypical depression in depressed
      outpatients and compared clinical and biological features of patients with
      atypical and nonatypical depression. METHOD: Depressed outpatients (N = 114) were
      diagnosed with the Schedule for Affective Disorders and Schizophrenia (SADS)
      according to Research Diagnostic Criteria. Patients were assessed for presence or
      absence of atypical depression with the Atypical Depressive Disorder Scale.
      Atypical depression was defined as the presence of mood reactivity during the
      depressive episode, along with at least one of four associated features:
      hypersomnia, hyperphagia, leaden paralysis, and rejection sensitivity. All
      patients completed the SCL-90 and were rated with the Hamilton Depression Rating
      Scale, extracted from the SADS. To assess biological functioning, the authors
      examined cortisol response to 75 mg of desipramine, a relatively selective
      norepinephrine reuptake inhibitor. RESULTS: Twenty-nine percent of patients met
      criteria for atypical depression. Patients with atypical depression were
      significantly more likely to be female. Patients with atypical and nonatypical
      depression did not differ on SCL-90 subscale scores. Although extracted Hamilton
      depression scale scores were significantly higher for patients with nonatypical
      depression, the difference was not clinically significant. Patients with atypical
      depression exhibited a significantly different cortisol response to desipramine
      injection than patients with nonatypical depression, which suggested that
      nonatypical depression may be associated with a more impaired norepinephrine
      system. CONCLUSIONS: In view of data in this study, as well as earlier studies,
      atypical depression has a unique symptom profile, may be widely prevalent, has a
      distinct treatment response, and may indicate a less impaired biological system
      than nonatypical depression. Since this is the first report to evaluate the
      frequency of atypical depression as well as the norepinephrine system in atypical
      depression, this study needs to be replicated. Nonetheless, the data support the
      inclusion of atypical depression as a subtype of the depressive disorders in DSM
      IV.

PMID- 7802118
TI  - Prevalence and correlates of dysthymia and major depression among patients with
      Alzheimer's disease.
AB  - OBJECTIVE: The purpose of this study was to examine the prevalence, risk factors,
      and correlates of depression among patients with Alzheimer's disease. METHOD: A
      consecutive series of 103 patients with probable Alzheimer's disease were
      examined with a structured psychiatric interview and were assessed for the
      presence of cognitive impairments, deficits in activities of daily living, social
      functioning, and anosognosia. RESULTS: Fifty-one percent of the patients had
      depression (28% had dysthymia and 23% major depression). Women had a
      significantly higher prevalence of both major depression and dysthymia than men.
      Depressed and nondepressed patients had a similar frequency of family and
      personal histories of depression, a similar frequency of personality disorders
      before the onset of depression, and no significant differences in cognitive
      deficits and impairment in activities of daily living. Dysthymia usually started
      after the onset of dementia and was significantly more prevalent in the early
      stages of dementia; patients with dysthymia had a significantly better awareness
      of intellectual deficits than patients with major or no depression. On the other
      hand, patients with major depression had an earlier onset of depression (half of
      them before the onset of dementia), and the prevalence of major depression was
      similar across the different stages of the illness. CONCLUSIONS: This study
      demonstrates a high prevalence of dysthymia and major depression among patients
      with probable Alzheimer's disease. While dysthymia may be an emotional reaction
      to the progressive cognitive decline, major depression may be related to
      biological factors.

PMID- 7802119
TI  - Alcoholism and affective disorder: clinical course of depressive symptoms.
AB  - OBJECTIVE: This study compared the severity of and the change in depressive
      symptoms among men with alcohol dependence, affective disorder, or both disorders
      during 4 weeks of inpatient treatment. METHOD: After their primary and secondary
      psychiatric disorders were defined with the use of criteria based on chronology
      of symptoms, 54 unmedicated men entering treatment for alcohol dependence or
      affective disorder were assessed for 4 consecutive weeks with the Hamilton
      Depression Rating Scale. RESULTS: The findings indicate that the rate of
      remission of depressive symptoms was consistent with the primary diagnosis.
      Depressive symptoms remitted more rapidly among the men with primary alcoholism
      than among those with primary affective disorder. However, a minimum of 3 weeks
      of abstinence from alcohol appeared to be necessary to consistently differentiate
      the groups with dual diagnoses on the basis of their current depressive symptoms.
      Alcohol dependence occurring in conjunction with primary affective disorder did
      not intensify presenting depressive symptoms or retard the resolution of such
      symptoms. CONCLUSIONS: Diagnoses of alcohol dependence and affective disorder
      based on symptom chronology appear to have prognostic significance with respect
      to remission of depressive symptoms in men with both diagnoses. Depressive
      symptoms of dysphoric mood, dysfunctional cognitions, vegetative symptoms, and
      anxiety/agitation showed different rates and levels of remission across the
      primary diagnostic groups.

PMID- 7802120
TI  - Neuropsychological functioning in detoxified alcoholics between 18 and 35 years
      of age.
AB  - OBJECTIVE: The authors determined 1) cognitive functioning in detoxified
      alcoholics who had alcohol-related problems for a relatively brief time and 2)
      relationships between neuropsychological test scores and recent and chronic
      alcohol consumption patterns, childhood symptoms of hyperactivity/minimal brain
      dysfunction, and extent of familial alcoholism. METHOD: The subjects were 101
      detoxified, drug-free alcoholics between 18 and 35 years of age who had consumed
      excessive amounts of alcohol (average of 114 g four to five times per week) for
      an average of 6 years. An average of 39 days after the last drink each alcoholic
      was given an extensive battery of neuropsychological tests assessing language
      skills, attention, motor skills, intelligence, memory, and cognitive functioning
      related to the frontal regions of the brain. RESULTS: Only four individuals
      evidenced mild cognitive dysfunction. Current psychiatric condition, anxiety and
      depressive states, and liver dysfunction were not related to cognition.
      Relationships of cognition of lifetime estimates of alcohol consumption (average
      of 189 kg) and number of days from last drink to testing were determined to be
      nonlinear and suggested that greater lifetime consumption predicted worse
      performance and that longer abstinence predicted better performance. Neither
      extent of familial alcoholism nor number of childhood signs and symptoms of
      hyperactivity/minimal brain dysfunction was predictive of cognition except that
      more antisocial behavior predicted poorer cognitive functioning. CONCLUSIONS:
      Cognition in young alcoholics, averaging 6 years of excessive alcohol
      consumption, was within normal limits, even though greater lifetime consumption
      predicted lower test scores and longer abstinence predicted higher scores.

PMID- 7802121
TI  - The contribution of neuropsychology to psychiatry.
AB  - OBJECTIVE: Neuropsychological test data are applied with increasing frequency in
      research studies and clinical practice in psychiatry. This article addresses
      three popular assumptions about neuropsychological test data and describes the
      limitations and contributions of neuropsychological assessment of patients with
      psychiatric disorders. METHOD: All research articles from major journals in
      psychiatry and clinical psychology since 1991 that focused on neuropsychological
      assessment of psychiatric patients were reviewed. Other journals and earlier
      studies were reviewed selectively. RESULTS: Neuropsychological test data have
      made significant contributions to the development of hypotheses about abnormal
      brain structure and function in patients with psychiatric disorders, yet many
      findings from neuropsychological assessments of psychiatric patients are
      misinterpreted. The extent to which neuropsychological test data in psychiatric
      populations can be interpreted to reflect abnormalities in brain structure and
      function is frequently exaggerated, as is the ability of neuropsychological
      measures to serve as specific cognitive probes in imaging studies of
      physiological activation. On the other hand, the utility of neuropsychological
      test batteries as measures of the patterns of cognitive strength and deficit in
      individuals with specific psychiatric disorders is frequently underestimated.
      CONCLUSIONS: In addition to testing models of regional brain dysfunction in
      psychiatric disorders, neuropsychological tests can provide researchers in
      psychiatry with an improved understanding of the relation between central
      cognitive impairments and symptoms and serve to identify cognitive predictors of
      course of illness, and they may provide a method for discriminating among
      heterogeneous forms of some psychiatric disorders. Clinically, neuropsychological
      test data can be used to develop treatment strategies tailored for an
      individual's specific cognitive strengths and deficits.

PMID- 7802122
TI  - Hypokalemia in outpatients with eating disorders.
AB  - OBJECTIVE: The literature on the prevalence and importance of hypokalemia in
      persons with eating disorders in contradictory and confusing. The authors
      investigated the frequency of hypokalemia and its relationship to symptoms in a
      group of outpatients with eating disorders. METHOD: Diagnostic evaluations and
      electrolyte studies were performed for 945 outpatients meeting the DSM-III-R
      criteria for eating disorders at the time of their intake evaluations at a
      suburban clinic for eating disorders. RESULTS: Clinically significant hypokalemia
      was comparatively rare. A total of 43 subjects (4.6%) were hypokalemic; of these,
      seven (0.7% of all subjects) were borderline hypokalemic (serum potassium = 3.4
      mmol/liter). The hypokalemic subjects had a significantly lower mean weight and
      body mass index at entry than the normokalemic subjects. Significantly more of
      the hypokalemic subjects purged by abusing laxatives, either alone or with
      vomiting. The patients with restricting (nonpurging) anorexia nervosa, even those
      whose weights were very low, were generally normokalemic. CONCLUSIONS: The low
      frequency of hypokalemia in this group of eating disordered outpatients suggests
      that routine electrolyte determination is a poor screening tool for occult or
      denied bulimia. Hypokalemia occurred almost invariably in lower-weight bulimic
      (or anorectic/bulimic) patients who were vomiting and/or abusing laxatives.
      Indeed, the study suggests that hypokalemia in a patient with an eating disorder
      is virtually certain evidence that the patient is purging at least daily. In
      addition, it appears that a patient with purely restricting anorexia nervosa is
      not at risk for hypokalemia even if his or her weight is very low.

PMID- 7802123
TI  - Anorexia nervosa and anorexic-like syndromes in a population-based female twin
      sample.
AB  - OBJECTIVE: The authors explored the epidemiologic characteristics and risk
      factors of anorexia nervosa and examined the relationship between narrowly
      defined anorexia nervosa and anorexia-like syndromes. METHOD: Structured
      interviews were administered to a population-based sample of 2,163 female twins.
      Anorexia nervosa was diagnosed by computer algorithm ("computer narrow") and by
      narrow and broad clinical definitions. RESULTS: Lifetime prevalence estimates of
      0.51%, 1.62%, and 3.70% were obtained for the computer narrow, clinical narrow,
      and clinical broad diagnoses, respectively. Dieting status, greater number of
      years of parental education, low self-esteem, high levels of neuroticism, and
      maternal overprotectiveness were significantly associated with anorexia nervosa.
      Both the pattern of comorbidity and the relationship to epidemiologic risk
      factors suggested an etiologic continuity between narrowly and broadly defined
      anorexic syndromes. Co-twins of twins with anorexia nervosa were at significantly
      higher risk for lifetime anorexia nervosa, bulimia nervosa, major depression, and
      current low body mass index. Significant comorbidity was found between anorexia
      nervosa and major depression, bulimia nervosa, generalized anxiety disorder,
      alcoholism, phobias, and panic disorder. CONCLUSIONS: The authors' analyses
      support the hypothesis of a spectrum of anorexic-like syndromes in women. These
      syndromes are familial and share familial etiologic factors with major depression
      and bulimia nervosa.

PMID- 7802124
TI  - Obsessive-compulsive disorder among patients with anorexia nervosa and bulimia
      nervosa.
AB  - OBJECTIVE: The present study sought to determine the prevalence of obsessive
      compulsive disorder among patients with eating disorders. METHOD: Ninety-three
      women who met DSM-III-R criteria for anorexia nervosa or bulimia nervosa were
      investigated by using a semistructured diagnostic interview, the Yale-Brown
      Obsessive Compulsive Scale, and the Eating Disorder Inventory. RESULTS: Thirty
      four patients (37%) met the DSM-III-R criteria for obsessive-compulsive disorder
      and also had a clinically significant score of 16 or higher on the Yale-Brown
      scale. These patients also had significantly higher, and hence pathological, mean
      scores on five of eight Eating Disorder Inventory scales than patients with
      eating disorders without concomitant obsessive-compulsive disorder. CONCLUSIONS:
      These results suggest that there is a high prevalence of obsessive-compulsive
      disorder among patients with anorexia and bulimia nervosa and that this
      prevalence may be correlated with the severity of the eating disorder.

PMID- 7802125
TI  - A family study of obsessive-compulsive disorder.
AB  - OBJECTIVE: The goal of this study was to determine 1) whether obsessive
      compulsive disorder is familial, 2) whether there is a familial relationship
      between obsessive-compulsive disorder and Gilles de la Tourette's syndrome and
      chronic tics, and 3) whether different familial types of obsessive-compulsive
      disorder exist. METHOD: In this family study, all available first-degree
      relatives of 100 probands with obsessive-compulsive disorder were interviewed
      directly with structured interviews, and best-estimate diagnoses were assigned.
      In addition to the 466 first-degree relatives of the probands, 113 comparison
      subjects who were first-degree relatives of 33 psychiatrically unaffected
      subjects were studied with the same interviews. RESULTS: The rates of obsessive
      compulsive disorder and subthreshold obsessive-compulsive disorder were
      significantly greater among the relatives of the probands with obsessive
      compulsive disorder (10.3% and 7.9%, respectively) than among the comparison
      subjects (1.9% and 2.0%, respectively). Furthermore, the rate of tics (Tourette's
      disorder and chronic tics) was also significantly greater among the relatives of
      the probands (4.6%) than among the comparison subjects (1.0%). The relatives of
      female probands with obsessive-compulsive disorder were more likely to have tics,
      and the relatives of probands with early onset were at higher risk for both
      obsessive-compulsive disorder and tics. CONCLUSIONS: Obsessive-compulsive
      disorder is a heterogeneous condition. Some cases are familial and related to tic
      disorders, some cases are familial and unrelated to tics, and in other cases
      there appears to be no family history of either obsessive-compulsive disorder or
      tics.

PMID- 7802126
TI  - Laboratory response of patients with panic and obsessive-compulsive disorders to
      35% CO2 challenges.
AB  - OBJECTIVE: The DSM-III-R anxiety disorders section includes both panic disorder
      and obsessive-compulsive disorder. To evaluate the relationship between these two
      disorders, subject responses to inhalation of a 35% CO2 and 65% O2 mixture were
      assessed. METHODS: Twenty-three patients with panic disorder, 23 with obsessive
      compulsive disorder, 12 with both obsessive-compulsive and panic disorder, and 23
      healthy comparison subjects were given a single vital capacity inhalation of 35%
      CO2 and 65% O2 or a placebo mixture of compressed air. A double-blind, random,
      crossover design was used. RESULTS: Patients with panic disorder and patients
      with both panic disorder and obsessive-compulsive disorder showed similar strong
      anxiogenic reactions to 35% CO2; while patients with obsessive-compulsive
      disorder alone did not differ from comparison subjects. CONCLUSIONS: These
      results confirm that obsessive-compulsive disorder and panic disorder are two
      distinct syndromes and that patients with these disorders have different
      sensitivity to CO2 inhalation.

PMID- 7802127
TI  - DSM-IV field trial: obsessive-compulsive disorder.
AB  - OBJECTIVE: Three issues relevant to revising the DSM-III-R criteria for obsessive
      compulsive disorder were examined in a field trial: 1) the requirement that
      symptoms of obsessive-compulsive disorder be viewed by the patient as excessive
      or unreasonable, 2) the presence of mental compulsions in addition to behavioral
      compulsions, and 3) ICD-10 subcategories. METHOD: The authors studied symptom
      patterns of obsessive-compulsive disorder as well as strength of obsessive belief
      among 431 patients with obsessive-compulsive disorder at seven hospital
      outpatient clinics. Two methods of subject selection were used: consecutive entry
      of everyone who contacted the clinics for evaluation of obsessive-compulsive
      disorder and entry of patients with obsessive-compulsive disorder who had
      continuing contact with the clinics since before the field trial and who were
      still symptomatic. Primary measures were the Yale-Brown Obsessive Compulsive
      Scale and face-valid questions about fixity of obsessive-compulsive beliefs.
      RESULTS: The large majority of patients were uncertain about whether their
      obsessive-compulsive symptoms were unreasonable or excessive, and most had both
      mental and behavioral compulsions. Results on the ICD-10 subcategories were
      equivocal. CONCLUSIONS: The present results converge with previous findings to
      indicate a broad range of insight among patients with obsessive-compulsive
      disorder. The DSM-III-R requirement for insight should be de-emphasized in DSM
      IV, and mental rituals should be included in the definition of compulsions.

PMID- 7802128
TI  - DSM-IV field trial: testing a new proposal for somatization disorder.
AB  - OBJECTIVE: The purpose of this study was to evaluate for APA a proposed strategy
      to diagnose somatization disorder for possible inclusion in DSM-IV. METHOD: Five
      sites--Washington University, University of Kansas, University of Iowa,
      University of Arkansas, and Mount Sinai Medical Center in New York--participated
      in a collaborative field trial. Female subjects (N = 353) were recruited from
      several different services (psychiatry, internal medicine, and family practice)
      and were evaluated for the presence or absence of the disorder. This assessment
      was performed with a new instrument constructed by combining all the criteria for
      somatization disorder from the proposed criteria for DSM-IV, DSM-III, DSM-III-R,
      Perley-Guze, and proposed criteria for ICD-10. RESULTS: A high level of
      concordance was found between the proposed diagnostic strategy for DSM-IV and the
      current criteria (DSM-III-R), as well as the earlier criteria (Perley-Guze and
      DSM-III). The ICD-10 criteria agreed poorly with all other criteria sets. The
      level of experience of the rater (expert versus novice) with the earlier (Perley
      Guze, DSM-III) and current (DSM-III-R) criteria did not influence the
      identification of cases by use of DSM-IV criteria. No racial effect was
      introduced by any of the criteria sets. CONCLUSIONS: The strategy for DSM-IV is
      an accurate and simpler method of diagnosing somatization disorder that does not
      require special expertise for proper use.

PMID- 7802129
TI  - The search for Harvey Cushing's patient, Minnie G., and the cause of her
      hypercortisolism.
AB  - The case of Harvey Cushing's historical patient, Minnie G, is now closed. Recent
      investigation has succeeded in identifying her, locating her death certificate,
      and finding her family. Information learned about the patient's personality is
      consistent with Cushing's assertion that her syndrome, although ameliorated, was
      persistent. The cause of her Cushing's syndrome remains unknown.

PMID- 7802130
TI  - A simple method for detecting subcutaneous phaeohyphomycosis with light-colored
      fungi. A study of eight cases.
AB  - Eight cases of subcutaneous phaeohyphomycosis are presented. A lack or scarcity
      of fungal pigmentation was seen in six of these cases. The simple act of lowering
      the microscope condenser makes these uncolored fungi easily visible. The thick
      hyaline capsule becomes refringent, presenting single oval or round cells and
      septated hyphae, which can be short or elongated, branched or unbranched, and
      irregularly swollen. The dematiacious character of the fungi is confirmed by
      using the Fontana-Masson stain. The fungi are not visible under polarized light.
      Our studies point to the probability of subcutaneous phaeohyphomycosis being a
      widespread tropical disease in Brazil. However, it is rarely diagnosed because of
      the common practice of fixing tissue specimens without prior culturing and the
      difficulties of detecting the fungal forms using customary microscopic
      procedures, especially when the fungi have a lack of pigment and are hard to
      detect by hematoxylin and eosin stain.

PMID- 7802131
TI  - Surgery fragments.

PMID- 7802132
TI  - Splenic angiosarcoma.

PMID- 7802133
TI  - Cutaneous follicular lymphoid hyperplasia with monotypic plasma cells. A
      clinicopathologic study of 18 patients.
AB  - Twenty cases of cutaneous follicular lymphoid hyperplasia with monotypic plasma
      cells are presented in a clinicopathologic study on 18 patients. The plaque-like
      or nodular lesions were solitary in 10 and multiple in eight patients.
      Immunohistochemistry showed well-defined B- and T-cell areas. Sheets of monotypic
      plasma cells occurred either interfollicularly or adjacent to the sclerotic
      stroma, with expression of IgG/kappa in 14 and IgG/lambda in six cases. In one
      patient with multiple lesions, one sample contained polyclonal plasma cells,
      whereas the other specimen showed light chain restriction. In another patient,
      disease recurred with a polytypic cutaneous plasma cell infiltrate. Polymerase
      chain reaction (PCR) revealed clonal immunoglobulin heavy chain gene
      rearrangements in eight of 13 cases, which was confirmed by Southern blot
      analysis in three samples. Clonal T-cell receptor chain gene rearrangements were
      not detected. Disease progression to overt malignant lymphoma did not occur
      within the follow-up period of up to 12 years, but recurrent disease was seen in
      three patients. Our data indicate that cutaneous lymphoid hyperplasia with
      monotypic plasma cells is a biologically distinct clinicopathological entity.

PMID- 7802134
TI  - Struma ovarii simulating ovarian tumors of other types. A report of 30 cases.
AB  - Thirty cases of struma ovarii with unusual microscopic features are described.
      They occurred in women 23 to 71 (average 49) years of age. Most of the patients
      had the usual symptoms and signs of an adnexal mass. Three patients had ascites
      and two had Meigs' syndrome. The tumors, all unilateral and confined to the
      ovary, ranged from 4 to 25 (average 12) cm in greatest dimension. They were
      typically predominantly solid and red-brown but cysts were present within foci of
      struma in several cases; an associated dermoid cyst was noted grossly in nine
      cases. Microscopic examination showed a prominent diffuse pattern in 21 cases,
      prominent microfollicles imparting in many cases a pseudotubular appearance in 20
      cases, abundant eosinophilic cytoplasm in nine cases, and abundant clear
      cytoplasm in four cases. A contiguous dermoid cyst which had not been recognized
      on gross examination was documented in five cases. The typical paucity of thyroid
      follicles in cellular areas of these tumors often caused either a failure to
      consider a diagnosis of struma ovarii or led to serious consideration of other
      diagnoses. Clues to the correct diagnosis were the presence of rare typical
      thyroid follicles in foci that were predominantly diffuse or pseudotubular, the
      presence of larger areas of typical struma in 22 cases, and the association with
      a dermoid cyst in 14 cases. Immunohistochemical staining for thyroglobulin
      confirmed the nature of the tumor in all five cases in which it was performed.
      The diagnosis of struma should be entertained when one is examining an ovarian
      neoplasm with solid or pseudotubular patterns or a content of oxyphilic or clear
      cells. A careful search for thyroid follicles should be undertaken to establish
      the diagnosis and immunohistochemical staining for thyroglobulin performed to
      confirm it in problematic cases.

PMID- 7802135
TI  - Verumontanum mucosal gland hyperplasia.
AB  - Prostatic adenocarcinoma of the small acinar type can be mimicked by benign
      proliferative lesions, such as atypical adenomatous hyperplasia (adenosis),
      sclerosing adenosis, nodular hyperplasia (cellular areas), lobular hyperplasia,
      basal cell hyperplasia, mesonephric hyperplasia, and nephrogenic adenoma. In our
      study, we describe another microacinar proliferation, which we have termed
      verumontanum mucosal gland hyperplasia (VMGH) because it occurs exclusively in
      the verumontanum and adjacent posterior urethra where the ejaculatory ducts and
      utricle empty into the urethra. We reviewed 341 radical prostatectomies and
      cystoprostatectomies done from 1988 through 1993 for prostate and bladder
      carcinoma, respectively. Forty-nine prostates (14%) from patients aged 47 to 87
      contained foci of VMGH. Of a total of 88 foci, a single lesion was present in 19
      cases and multiple lesion in 30 cases. Fifty-nine of the foci arose around the
      ejaculatory or prostatic ducts, 17 from around the utricle, and 13 from adjacent
      posterior urethral mucosa. Individual lesions were quantified as to the number of
      acini per focus as follows: 6 to 10 in 28 (1+), 11 to 25 in 29 (2+), 25 to 50 in
      16 (3+), and more than 50 in 15 (4+). No crystalloids or intraluminal mucin were
      seen, but; intraluminal corpora amylacea, usually numerous, were present in 57 of
      the 88 voci. The microacini were frequently "back to back" architecturally. The
      lining epithelium consisted of bland cuboidal to columnar luminal cells with
      underlying basal cells. VMGH, a previously undescribed benign microacinar
      proliferation, occurs in a very restricted and specific location and appears to
      be unrelated to other lesions with which it may be confused.

PMID- 7802136
TI  - Meningiomas and gliomas in juxtaposition: casual or causal coexistence? Report of
      two cases.
AB  - Two cases of meningioma and glioma established in biopsy material from one or
      more than one operation are reported. In these cases, an originally benign
      meningioma was followed by the development of anaplastic astrocytoma in close
      juxtaposition to the site of first operation. The close juxtaposition of two
      histologically different tumors suggested that one of them might lead to local
      proliferation and independent growth of the other.

PMID- 7802137
TI  - Infrequent association of Epstein-Barr virus with CD30-positive anaplastic large
      cell lymphomas from American and Asian patients.
AB  - CD30 (Ki-1)-positive anaplastic large cell lymphoma (CD30+ ALCL) is a
      morphologically and immunophenotypically distinct subset of non-Hodgkin's
      lymphoma. Although the presence of Epstein-Barr virus (EBV) has been well
      documented in a significant proportion of cases of Hodgkin's disease, another
      CD30+ malignancy, few studies have examined the association of EBV with CD30+
      ALCL. These latter studies have produced conflicting findings. To further
      investigate the existence of a putative association of EBV with CD30+ ALCL, and
      whether this association, if present, shows geographic variation, we examined 34
      formalin-fixed, paraffin-embedded specimens from cases of CD30+ ALCL from the
      United States and Hong Kong. Immunophenotypically, 15 cases were of B lineage, 15
      cases were of T lineage, one case expressed both B- and T-cell markers, and three
      were of null lineage. A highly sensitive in situ hybridization method was
      performed with use of an antisense oligonucleotide probe to the EBV-encoded RNA
      (EBER-1). EBV-RNA was identified in 3 of 14 CD30+ ALCL specimens from Hong Kong
      patients and in 1 of 20 from the American patients. The EBER-1 signal was present
      in all or virtually all of the tumor cell nuclei in the three EBV-RNA-positive
      CD30+ ALCL Hong Kong cases, but was only focally present in the single EBV
      positive American case. The latent membrane protein-1 (LMP1) of EBV was
      identified in only one of the four positive cases, a Hong Kong case. Our results
      suggest that in contrast to Hodgkin's disease, EBV has no significant association
      with CD30+ ALCL.

PMID- 7802138
TI  - Feminizing Sertoli cell tumors in boys with Peutz-Jeghers syndrome.
AB  - We report the pathology findings in two cases of multicentric Sertoli cell
      testicular tumors in two young boys with probable Peutz-Jeghers syndrome. Four
      cases of such tumors occurring in boys with Peutz-Jeghers syndrome were
      previously reported. Each of the two boys reported in this paper had prominent
      gynecomastia, rapid growth, and advanced bone age. Serum levels of estradiol were
      markedly elevated. Anti-mullerian hormone was measured in the serum of one of the
      boys and was in the normal range for age. Bilateral orchiectomy was performed in
      each case because the neoplastic growth would most likely result in sterility,
      and curtailment of height potential was threatened from continued elevation of
      estradiol levels. Microscopically, greatly enlarged seminiferous tubules packed
      with ovoid Sertoli-like cells were present. Prominent eosinophilic basement
      membrane surrounded the tubules and intersected between the cells, forming
      hyalinized ovoid globules and microcalcifications. Ultrastructure revealed
      lamination of basement membranes surrounding adjacent cells, ovoid cells with
      abundant cytoplasm, and limited smooth endoplasmic reticulum. Studies of
      testicular tumor tissue from both cases revealed increased transcription of the
      aromatase cytochrome P450 gene using promoter II, the promoter directing
      aromatase expression in the normal ovary and testis. The levels of transcripts
      were comparable to corpus luteum, thus resulting in increased estrogen synthesis.
      Transcripts specific for placental-type aromatase promoters (I.1 and I.2) were
      not detected in significant levels in these tumors.

PMID- 7802139
TI  - Gastrointestinal stromal tumors with prominent myxoid matrix. Clinicopathologic,
      immunohistochemical, and ultrastructural study of nine cases of a distinctive
      morphologic variant of myogenic stromal tumor.
AB  - Nine cases are presented of a distinctive morphologic variant of myogenic
      gastrointestinal stromal tumor characterized by an unusually prominent myxoid
      stromal background reminiscent of a neural neoplasm but lacking the
      immunohistochemical or ultrastructural features of peripheral nerve sheath or
      ganglionic differentiation. The patients included six women and three men aged 42
      to 86 years (mean, 70). The lesions occurred in the stomach (seven cases) and
      small intestine (two cases) and ranged in size from 2.5 to 9.5 cm. They were
      described grossly as well circumscribed, unencapsulated, with a prominently
      myxoid and often cystic cut surface. Histologically, the lesions were composed of
      a proliferation of round, spindle, or stellate cells embedded in an abundant
      myxoid stroma. Histochemical stains showed strong positive reaction of the myxoid
      stromal background with alcian blue at pH 2.5; this staining reaction was
      abolished by treatment with hyaluronidase, indicating an abundance of connective
      tissue mucosubstances rich in hyaluronic acid. Immunohistochemical stains showed
      strong positivity of the tumor cells with vimentin antibodies in all cases and
      focal weak to moderate positive staining with muscle actin (HHF35) in eight cases
      and with desmin in two. Stains for keratin, S-100; epithelial membrane antigen,
      and collagen type IV were uniformly negative. Ultrastructural examination carried
      out in all cases showed features consistent with those previously described for
      myogenic gastrointestinal stromal tumors, namely, scattered mitochondria and
      prominent Golgi apparati, strands of rough endoplasmic reticulum, focal
      accumulation of intracytoplasmic microfilaments with occasional focal
      condensations, subplasmalemmal attachment plaques and immature cell junctions,
      focal extracellular basal lamina material, and surface-oriented micropinocytotic
      activity. The myxoid changes observed in these tumors may represent a secondary,
      nonspecific reaction pattern of the tumor cells to some noxious stimulus, or they
      may be a form of degenerative phenomenon such as that commonly observed in smooth
      muscle tumors of the uterus and other sites. Myogenic gastrointestinal stromal
      tumors with prominent myxoid stroma should be distinguished from benign
      schwannoma of the stomach and gastrointestinal autonomic nerve tumors. Because of
      the differences in prognosis for these entities, immunohistochemical and
      ultrastructural examinations are recommended for the evaluation of
      gastrointestinal stromal neoplasms with prominent myxoid features.

PMID- 7802140
TI  - Sclerosing cholangitis following human orthotopic liver transplantation.
AB  - Sclerosing cholangitis defined by cholangiographic criteria may occur after
      orthotopic liver transplantation. In this retrospective study, we analyzed failed
      grafts and antecedent serial biopsies of 24 patients who developed this type of
      nonanastomotic biliary strictures. Sclerosing cholangitis was histologically
      diagnosed if there was a combination of periductal fibrosis and features of large
      bile duct obstruction. The condition was observed in all but one available failed
      allografts. This later showed ischemic-type lesions without periductal fibrosis.
      Liver biopsy specimens were nondiagnostic relative to sclerosing cholangitis,
      although 85% of the patients had evidence of large bile duct obstruction.
      Numerous associated factors may explain the pathogenesis of secondary sclerosing
      cholangitis: an immunologically related etiologic factor (10 recipients of ABO
      incompatible allografts) and compromised arterial blood flow that likely resulted
      from hepatic artery thrombosis (12 patients), focal arterial fibrointimal
      hyperplasia (three patients), chronic ductopenic arteriopathic rejection (three
      patients) and/or preservation-related ischemia (four patients). Sclerosing
      cholangitis may be a significant cause of graft failure that often has misleading
      biopsy manifestations. From a practical standpoint, cholestasis with evidence of
      large bile duct obstruction warrants cholangiographic assessment of the biliary
      tree.

PMID- 7802142
TI  - [Acute stage of spinal injury (physiopathology). "Ischemic damage to the spinal
      cord"].
AB  - Several pathophysiological events follow spinal cord trauma. Vascular abnormality
      and changes in spinal cord blood perfusion occur immediately after injury
      primarily within the gray matter. Progressive biochemical and histological
      alterations take place both in gray and white matter subsequently. The
      significant metabolic and ionic alterations, all of which are interdependent
      (reduction in energy substrate, enzymes and neurotransmitters release
      alterations, ionic fluxes changes) result either in loss of functional activity
      or structural integrity in the injured spinal cord and remains a matter of
      speculation.

PMID- 7802141
TI  - Clear cell carcinomas of the gallbladder and extrahepatic bile ducts.
AB  - Although clear cell carcinomas have been described in numerous anatomic sites,
      their occurrence in the gallbladder and extrahepatic bile ducts (EHBD) is
      practically unknown. We report 10 such cases. Seven arose in the gallbladder and
      three in the EHBD; all patients with gallbladder tumors were females with
      cholelithiasis whose ages ranged from 56 to 68 years. Patients with EHBD tumors
      were younger (38 and 40 years of age) and had extrahepatic biliary obstruction
      and abdominal pain. Two patients with gallbladder carcinomas had elevated serum
      carcinoembryonic antigen (CEA) levels, and another without hepatic involvement
      had markedly elevated circulating levels of alpha-fetoprotein (AFP).
      Histologically, nine tumors were adenocarcinomas and one was a squamous cell
      carcinoma. Seven adenocarcinomas consisted of cords, sheets, nests, papillae, and
      trabeculae of clear cells with well-defined cytoplasmic borders. Two were
      composed predominantly of glands and papillary structures. The cells contained
      PAS-positive diastase-labile granules and were cytokeratin- and EMA-positive and
      immunoreactive for erythropoiesis-associated antigen. One gallbladder tumor
      contained areas of hepatoid differentiation, a feature described in gallbladder
      neoplasms only once before. These areas were AFP-positive and immunoreactive for
      CEA. By electron microscopy, they showed hepatoid differentiation with formation
      of bile canaliculi. In two gallbladder tumors, neoplastic cells contained
      subnuclear vacuoles reminiscent of early secretory endometrium. Foci of
      conventional adenocarcinoma or mucinous carcinoma were recognized in all nine
      tumors. The squamous cell carcinoma showed only foci of squamous differentiation
      with keratinization. The clear cells of this neoplasm had a trabecular and solid
      growth pattern. These clear cell neoplasms of the gallbladder and EHBD must be
      differentiated from metastatic renal cell carcinoma, based upon the presence of
      areas of conventional adenocarcinoma or foci of squamous differentiation since
      results of special stains and immunohistochemistry are similar in both neoplasms.
      One of the patients with EHBD carcinoma is alive and symptom-free 6 years
      following right hepatic lobectomy. Five patients with gallbladder tumors had
      direct extension into the liver and died with metastases. Two are living with
      metastases.

PMID- 7802143
TI  - [Spinal cord injuries: comments on preventive and curative strategy].
AB  - Research for the cure for paralysis caused by spinal cord injury has followed
      three complementary lines: Limitation of secondary lesions; the use of
      antagonists of excitatory amino acids has proven affective in reducing the extent
      of the lesions. Control of the glial scar; an oxygenated derivative of
      cholesterol can reduce the proliferation of reactive astrocytes and their
      hypertrophy, and permit the regrowth of axons in a denervated territory.
      Transplantation of embryonic neurons below the lesion allows to reinnervate
      denervated sites and reestablish reflex functions.

PMID- 7802144
TI  - [Effects of propofol on middle latency auditory evoked potentials].

PMID- 7802145
TI  - Neurophysiological effects of diisopropylphenol evaluated with somatosensory and
      motor evoked potentials.

PMID- 7802146
TI  - [Power spectrum analysis in the study of sympathetic and vagal activities in
      patients with tetraplegia].

PMID- 7802147
TI  - [Neurological pain].
AB  - Neurogenic pain is by definition linked to a lesion of the pain pathways at any
      level. There are many causes for the neurological pain which can be present in
      sympathetic disorders, in peripheral neuropathies and central nervous disorders
      too. In despite of these multiple aetiologies, the neurological pain is
      characterised by: demyelinisation at the anatomic lesion; a spontaneous firing
      described by the authors as related to three mechanisms, sensitivation,
      deafferentation and lost of inhibition; a common and specific clinical semiology
      very different indeed from the peripheral pain described as a surafferentation.

PMID- 7802148
TI  - [Stimulation techniques in chronic pain secondary to spinal nerve and/or spinal
      cord injuries].

PMID- 7802150
TI  - [An original technique of preoperative intentional normovolemic hemodilution].

PMID- 7802149
TI  - [Functional neurosurgery of chronic pain: nociceptive tracts ablation at the
      level of the peripheral nervous system and spinal cord].
AB  - This article is devoted to ablative neurosurgical procedures used for the
      treatment of chronic pain. The procedures are classified as those directed to the
      cranial nerves, the peripheral nerves, the spinal roots, the dorsal root entry
      zone and the ascending spino-reticulo-thalamic pathways. The rational and
      neurophysiological effects of these operations are stressed. The actual
      indications for each procedure are specified.

PMID- 7802151
TI  - [Comparison of 4 anesthesia induction protocols on hemodynamic changes in
      tracheal intubation].
AB  - This study was undertaken to determine whether alfentanil (A) or sufentanil (S)
      associated with propofol (P) or etomidate (E) can abolish or attenuate the
      hemodynamic response to laryngoscopy and orotracheal intubation in ASA I or II
      patients, during induction of anesthesia for lumbar spinal surgery. Eighty
      patients were randomly divided into four groups. Group I (AE) received alfentanil
      30 micrograms/kg and etomidate 0.3 mg/kg; group II (AP) received alfentanil 30
      micrograms/kg and propofol 1.5 mg/kg; group III (SE) received sufentanil 0.3
      microgram/kg and etomidate 0.3 mg/kg; group IV (SP) received sufentanil 0.3
      microgram/kg and propofol 1.5 mg/kg. In each group, narcotic and hypnotic were
      given respectively five minutes and three minutes before laryngoscopy. The
      intubation was facilitated by vecuronium 0.1 mg/kg. The sequence of laryngoscopy
      and orotracheal intubation was always performed in less than 20 seconds. The
      anesthesia was maintained by O2/N2O in IPPV (TV = 10 ml/kg; respiratory rate 12).
      Heart rate, systolic, diastolic and mean blood pressure were recorded at the
      following times: on arrival in the operating room (T-5), 3 minutes before
      laryngoscopy (T-3), just at laryngoscopy (T0) and 1 (T1), 3 (T3), 54 (T5) minutes
      after intubation. The comparison of baseline values (T-5) with T1 values showed
      that the heart rate did not change significantly in any group. Systolic blood
      pressure increased (p < 0.05) in SE group, decreased (p < 0.05) in AE and SE
      groups and did not change in AP and SP groups. Mean blood pressure increased in
      AE and SE groups, decreased in AP group but did not change significantly in SP
      group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7802152
TI  - [Is the malleable mattress harmful for the spinal cord?].
AB  - When the inside pressure of mouldable mattress is lowered isotropic deformation
      can be harmful for spinal cord. The axial force is measured placing stress gauge
      in a metallic manikin and in corpse (T2-L1), then on the cephalic top of
      volunteers. When soles and head are included in an usual mattress, during the
      retraction stress values raise up to 484 N at 262 mbar for manikin, to 150 N at
      315 mbar for corpse, to 102 N at 310 mbar for cephalic top of the volunteers. In
      comparison, a prototype was tested. Results were improved on metallic models but
      not on human corpses or volunteers. This test allowed us a better understanding
      of the mechanism of the stress. It is possible to propose precautionary measures
      during patient immobilization (to provide a space between soles, head and
      mattress) and to build a new stressless mattress.

PMID- 7802153
TI  - [Patients with high spinal cord injuries: evaluation of diaphragmatic function,
      indication of electrophrenic ventilation].
AB  - Electrophrenic Respiration (REP) is a technic specially reserved to the patients
      with a first motoneuron disease but having moreover normal phrenic nerve,
      diaphragm and lungs. Electrical pulse trains are applied to the phrenic nerve by
      a surgically implanted electrode. They produce rhythmic inspiratory diaphragm
      contractions; expiratory time is passive. The energy is delivered by a
      transcutaneous radiofrequency external pacer. Before to decide to implant a REP
      device, it should be wait for a sufficient time to avoid either a possible return
      to a spontaneous breathing or, on the contrary, a peripheral nerve disease
      initially unrecognized. After regularly repeated external detection exams,
      surgery must be done gently on a stabilised patient, out of infection and, if
      possible, without intellectual trouble. The training needs a long time (many
      months) since to become fatigue-resistant a paced muscle must be trained
      progressively and durably. In that way the results are generally good, as the 13
      patients we have implanted may give an evidence.

PMID- 7802154
TI  - [Medical treatment of spinal cord injury during the acute phase. Effect of a
      calcium inhibitor].
AB  - Post traumatic ischemia appears to be largely involved for the extension of
      lesions in acute injury of the spinal cord. The present study evaluate the
      putative improvement of spinal cord blood flow (S.C.B.F.) by calcium channel
      blocker after acute spinal cord injury in baboons. S.C.B.F. measured by a
      scannographic technique with 133Xe were realised each thirty min for 4 hours and
      seven days later; somatosensory evoked potentials (S.E.P.) magnetic resonance
      imaging (M.R.I.) and histological study of the spine were realised at different
      time of the experimentation. Ten monkey were used. Acute trauma was achieved by
      compression of the cord at T1 by applying a 2.10(2) kPa (2 bar) pressure for 5 s
      with a balloon catheter inflated with Ringer's solution. Then, five monkeys
      received saline infusion for seven days and the other five received a nimodipine
      infusion (0.04 mg.kg-1.h-1) during the same time. Nimodipine improved
      significantly S.C.B.F. Two monkeys in the treated group showed improvement of
      axonal function as judged by S.E.P. Conversely no significant difference was
      noted by R.M.I. although the histological study showed smaller lesions in the
      treated group. Nimodipine could represent in the next years a new medical
      treatment in acute spinal cord injury in man.

PMID- 7802155
TI  - Alaska/Russian Far East behavioral health projects: a progress report on recent
      activities.
AB  - A number of "behavioral health" exchange activities between Alaska and the
      Russian Far East took place during 1992-93. These included visits by a
      psychiatrist running one of the first "private polyclinics" in Magadan and by a
      narcologist to discuss the latest developments in alcohol services; a Behavioral
      Health Conference where Native health workers from Russia and Alaska shared
      experiences; beginning a multi-year epidemiology project; and a project to assess
      needs for a fetal alcohol syndrome (FAS) prevention program in Magadan.

PMID- 7802156
TI  - Russian oral health initiative--Magadan region and Seymchan.

PMID- 7802157
TI  - Alaska/Russian Far East women's health and family planning.

PMID- 7802158
TI  - Alaska/Magadan radiology project update.

PMID- 7802159
TI  - Proceedings of the Alaskan and Russian Natives' Health and Social Issues
      Conference Alaska.
AB  - An Alaska-Russia Native People's Health and Social Issues Conference, sponsored
      by the Alaska Department of Health and Social Services, the Alaska Native
      Foundation, the University of Anchorage Institute for Circumpolar Health Studies,
      The International Scientific Center 'ARTIKA' (Magadan, Russia), the Associations
      of Native People of Chukotka and Kolyma, and the Magadan Native Association, was
      held in Wasilla, Alaska in May, 1992. The conference brought together Native
      people, primarily health and social services workers, to discuss differences and
      similarities in issues and approaches, and to lay the foundation for future
      collaboration. The primary participants came mostly from rural villages and small
      regional cities, and represented Native Health Corporations, Native Associations,
      and villages. Additional participants came form the University of Alaska, the
      Alaska Department of Health and Social Services, the Indian Health Service, the
      Magadan Health Department, the Inuit Circumpolar Conference, and the
      International Circumpolar Health Union. A total of 39 people participated,
      including: eight Russian Natives (Chukchi, Even, and Siberian Yup'ik); three non
      Native Russians; 18 Alaska Natives (Aleut, Athabaskan, Inupiat, Siberian Yup'ik,
      Yup'ik); nine non-Native Alaskans; one Canadian. The issues discussed in
      individual and panel presentations, and in small groups, included history,
      demography, settlement patterns, the cash and subsistence economies, mental and
      physical health (epidemiology, etiology, treatment and prevention), education,
      governance, culture and language.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7802160
TI  - Self-reported illness among travelers to the Russian Far East.

PMID- 7802161
TI  - Social-political and medical-psychological aspects of life of the Native people
      of the north.

PMID- 7802162
TI  - Substance abuse problems in the Magadan Region of the Russian Far East.
AB  - People in the Magadan Region are hopeful that citizens of Alaska will make
      contact with Native peoples, especially in the Magadan region. Right now, rates
      of alcohol-related problems are high and economic difficulties are leading to
      cutbacks in existing programs (see Chart 2). Alaskans have much good experience
      and information to share, and there is a lot that can be accomplished, as
      illustrated by the story of the recovering woman, and her influence upon people
      by example. Dynamics of the morbidity of alcoholism and alcoholic psychosis in
      regions of Siberia and the Far East. Chart 3 shows dramatic rises in
      alcoholism/alcoholic psychosis rates between 1965 and 1985. On the scale used,
      rates were about 20 per 10,000 in 1965, and in 1985 were about 250 per 10,000.
      Rates appear to be higher in the Far East, to be second highest in Western
      Siberia, and to be slightly lower in Eastern Siberia. Rates for Russia as a whole
      seem to have followed the same general trend towards rising, but are somewhat
      lower than the rates given for Siberia and the Soviet Far East. Two questions
      arise out of this data: 1. Why the increase since 1965? 2. Why worse in the Far
      East?

PMID- 7802163
TI  - Papulonecrotic tuberculid. A clinical, histopathological, and immunohistochemical
      study of 15 patients.
AB  - We report 10 women and five men with papulonecrotic tuberculid, an uncommon form
      of cutaneous tuberculosis (TB). The mean age was 22.6 years (range, 2 1/2-35
      years) at presentation. The Mantoux test was strongly positive in 13 patients.
      Five patients showed presumptive evidence of associated TB; in one case, the
      presence of TB was proven by culture. Response to anti-TB was dramatic in all
      cases. Clinical findings were similar to those previously published. We emphasize
      the simultaneous occurrence of erythema induratum, associated Takayasu's disease,
      possible associated phlebitic tuberculid, and clinical mimicry of acute bacterial
      endocarditis. The main histopathological findings obtained from 27 biopsy
      specimens included dermal necrosis (26 of 27 cases), a poorly formed
      granulomatous infiltrate (27 of 27 cases), vasculitis (11 of 27 cases),
      perivascular spongy edema (11 of 27 cases), and follicular necrosis or
      suppuration (five of 27 cases). A Ziehl-Neelsen stain was negative in all biopsy
      specimens. Immunohistochemical labeling revealed a preponderance of T-lymphocytes
      (UCHL-1+), monocytes-macrophages (S-100+), and Langerhans cells (ACT+),
      indicative of a type IV hypersensitivity reaction. B-lymphocytes (L26+) were
      sparse. Conditions that may be confused with PNT on clinical or histopathological
      ground include pityriasis lichenoides et varioliformis acuta, papular urticaria,
      papulopustular syphilide, miliary TB, septicemia, perforating granuloma annulare,
      chondrodermatitis nodularis, reactive perforating collagenosis, allergic
      granulomatosis, suppurative folliculitis, and infectious causes of palisading
      granulomas. Papulonecrotic tuberculid has distinct clinical, histopathological,
      and immunohistochemical features. Awareness of this entity is important since an
      appropriate diagnosis is necessary for the institution of timely curative
      treatment.

PMID- 7802164
TI  - Immunolocalization of low-molecular-weight stress protein HSP 27 in normal skin
      and common cutaneous lesions.
AB  - Stress proteins, which are found ubiquitously in mammalian cells, appear to be
      implicated in the regulation of cell growth and protection from environmental
      insult. Although we previously demonstrated the expression of low-molecular
      weight stress protein, HSP 27, in cultured keratinocytes, HSP 27 has not yet been
      identified in human skin. Using standard immunohistochemistry on routinely
      processed paraffin sections, we examined specimens of common epidermal lesions
      and normal skin with a monoclonal antibody to HSP 27. Normal skin from the
      breast, foreskin, and lower extremity demonstrated strong cytoplasmic staining in
      the suprabasal epidermis. There was no change in the intensity of staining or
      cellular localization related to age, body location, or gender. Sections of
      actinic keratosis, superficial basal cell carcinoma, seborrheic keratosis, and
      psoriasis also exhibited strong cytoplasmic staining in the suprabasal layers of
      the epidermis. In contrast, cutaneous squamous cell carcinoma demonstrated only
      weak cytoplasmic staining throughout the infiltrating tumor. This is of
      particular interest, since other investigators have reported a loss of HSP 27
      expression in oncogenically transformed cells that exhibit a tumorigenic
      phenotype. To our knowledge, this study provides the first demonstration of HSP
      27 expression in human skin.

PMID- 7802165
TI  - Chronic actinic dermatitis. An immunohistochemical study of its T-cell antigenic
      profile, with comparison to cutaneous T-cell lymphoma.
AB  - Chronic actinic dermatitis (CAD) describes a persistent photosensitivity disorder
      in the absence of continued exposure to photosensitizers; it is characterized by
      a T-cell infiltrate within the epidermis and dermis. The purpose of this study
      was to characterize the T-cell infiltrate better immunohistochemically. Serial
      cryostat sections of fresh-frozen punch biopsy specimens of skin were analyzed in
      11 patients with CAD and 3 patients with erythrodermic cutaneous T-cell lymphoma
      (CTCL). Monoclonal antibodies against the pan T-cell, pan B-cell, and T-cell
      subsets and the T cell-receptor (TCR) antigens were used. CD8-positive (T
      suppressor-cytotoxic) cells were predominant in the epidermis of CAD, while CD4
      positive (T-helper) cells were predominant in the epidermis and dermis of CTCL.
      CDw29-positive (T-memory) cells were predominant in all cases. The number of BF1
      (beta-chain constant region of the TCR)-positive cells approximated the number of
      CD3-positive cells in all CAD cases but was significantly lower than the number
      of CD3-positive cells in two of three cases of CTCL. There was no clustering or
      preferential staining with any of the beta-chain variable-region antibodies in
      any of the specimens. These results indicate that CAD has a characteristic
      immunophenotype distinct from that of most cases of CTCL and that discordance
      between BF1 and CD3 expressions did not occur in the CAD cases.

PMID- 7802166
TI  - "Eczema" revisited. A status report based upon current textbooks of dermatology.

PMID- 7802167
TI  - Plexiform xanthomatous tumor. A report of three cases.
AB  - We describe three cases of plexiform xanthomatous tumor in middle-aged men. The
      tumors shared some morphological features with xanthoma, cholesterotic fibrous
      histiocytoma, and plexiform fibrohistiocytic tumor. However, no
      hyperlipoproteinemia was found in our cases, and many morphological features
      distinguish the plexiform xanthomatous tumor from all the other entities.

PMID- 7802168
TI  - Plexiform granular cell tumor. A report of two cases.
AB  - A previously undescribed variant of granular cell tumor with an interesting
      plexiform pattern was found in the lower leg of a 10-year-old girl and on the
      back of a 12-year-old girl. Clinically, the patients presented with intradermal
      plaques that were accompanied by variable degrees of pain or tenderness.
      Histopathologic examination revealed granular cell tumors with various sized
      fascicles, particularly around nerve bundles, in a plexiform pattern. Cytoplasmic
      granules were PAS positive. Immunohistochemical studies showed tumor cells to be
      strongly positive with S-100 protein and weakly positive with alpha-1
      antichymotrypsin and vimentin. These findings offer further support for a neural
      origin for granular cell tumors.

PMID- 7802169
TI  - Woringer-Kolopp disease. A lymphomatoid hypersensitivity reaction.
AB  - We report two cases of unilesional pagetoid reticulosis (Woringer-Kolopp
      disease). Histopathological, immunohistological, ultrastructural, and genotypic
      studies showed both lesions to be lymphomatoid hypersensitivity reactions, as
      characterized by polyclonal proliferations of T-lymphocytes; CD8+ T cytotoxic
      suppressor (Tc/s) lymphocytes were predominant in one case, whereas CD4+ T helper
      (Th) lymphocytes were predominant in the other. The nosology of Woringer-Kolopp
      disease is discussed.

PMID- 7802170
TI  - Extensive unilateral speckled lentiginous nevus.
AB  - We report a case of speckled lentiginous nevus with extensive unilateral
      distribution in a 53-year-old man. The lesions involved the left back, extending
      from the midline anteriorly to the thorax, arm, and forearm. The background
      pigmentary patch covered only the back and upper arm. Histologic examination
      revealed a lentiginous pattern as well as a congenital nevocytic pattern, even in
      the areas where the background was nontanned skin. This combined clinical pattern
      in the same patient fits the descriptions for both the usual and unusual speckled
      lentiginous nevus. Cases with variants of extensive unilateral distribution are
      infrequent and pathologists should pay particular attention to them because of
      the possibility of their malignant transformation.

PMID- 7802171
TI  - Secondary anetoderma involving a pilomatricoma.
AB  - We describe an 11-year-old girl with secondary anetoderma involving a
      pilomatricoma. She presented with a soft, wrinkled pedunculated lesion overlying
      a firm subcutaneous mass on her right anterior shoulder. Pathologic examination
      revealed a pilomatricoma in the subcutaneous tissue, with focal loss of elastic
      fibers in the overlying dermis. Secondary anetoderma has been reported to involve
      various infections, inflammatory disorders, and tumors, but the association with
      pilomatricoma is very rare.

PMID- 7802173
TI  - Nevus with cyst and nevus with folliculitis.

PMID- 7802172
TI  - A critical analysis of textbooks of dermatopathology in historical perspective.
      Part 15.

PMID- 7802174
TI  - The medical fast-track.

PMID- 7802175
TI  - The effect of laryngoscopy of different cervical spine immobilisation techniques.
AB  - Fifty patients underwent laryngoscopy with two different cervical spine
      immobilisation techniques. First the cervical spine was immobilised in a rigid
      collar with tape across the forehead and sandbags on either side of the neck,
      then with an assistant providing manual in-line immobilisation. Finally, patients
      underwent laryngoscopy in the routine intubating position. In 56% of patients the
      view of the larynx improved by one grade and in 10% the view improved by two
      grades when manual immobilisation was substituted for the collar, tape and
      sandbags (p < 0.0001). There was a poor view on laryngoscopy (grade 3 or 4) in
      64% of patients when immobilised in a collar, tape and sandbags compared to 22%
      of patients undergoing in-line manual immobilisation (p < 0.001). Mouth opening
      was significantly reduced when patients were wearing cervical collars and this
      was the main factor contributing to the increased difficulty of laryngoscopy in
      this particular form of cervical spine immobilisation. It is recommended that
      manual in-line immobilisation should be the method of choice for cervical spine
      stabilisation during tracheal intubation.

PMID- 7802176
TI  - Comparative effects of laryngeal mask and tracheal tube on total respiratory
      resistance in anaesthetised patients.
AB  - We compared the effects of the laryngeal mask and tracheal tube on total
      respiratory resistance in 10 anaesthetised, mechanically ventilated patients
      undergoing otological microsurgery. The subjects were randomly divided into two
      groups. In the first group, the tracheal tube (Rusch) was inserted for the first
      series of measurements. This was then replaced by a laryngeal mask (Intavent) and
      a second series of measurements was made during the first hour of operation. In
      the second group, the same protocol was applied with inverse order in the use of
      the devices. From the measurement of respiratory flow and pressure at the airway
      opening, total respiratory resistance was calculated by multiple linear
      regression. The data were corrected to eliminate the previously determined
      nonlinear resistance of the two devices. Arterial blood pressure,
      electrocardiogram, oxygen saturation and end-tidal carbon dioxide concentration
      were continuously monitored. With the laryngeal mask and the tracheal tube, mean
      (SE) minute ventilation was 9.4(0.9)l.min-1 and 8.1(0.9)l.min-1, respectively for
      end-tidal carbon dioxide concentrations between 3.6 and 4.1%. Although the
      glottic resistance was included in the measurement performed with the laryngeal
      mask but not with the tracheal tube, mean (SE) total respiratory resistance was
      not significantly different with the two devices (0.61(0.32) and 0.69(0.35) kPa.l
      1.s, respectively). Leakage was avoided with the laryngeal mask because the
      insufflation pressure never exceeded 1.7 kPa except in one patient suffering from
      severe chronic obstructive pulmonary disease who had a total respiratory
      resistance of 1.45 kPa.l-1.s. During the first hour of the operation all
      respiratory variables remained stable irrespective of the device used.

PMID- 7802177
TI  - Plasma concentrations of alfentanil following epidural administration.
AB  - The plasma concentration-time profile of alfentanil following epidural
      administration was determined in eight patients undergoing lower abdominal
      surgery under nitrous oxide (66%)-oxygen (33%)-halothane (0.3%) anaesthesia,
      supplemented with intravenous sufentanil. Alfentanil (1 mg) was administered
      epidurally before induction of general anaesthesia. Blood samples for the
      determination of plasma alfentanil concentrations by capillary gas chromatography
      were collected at intervals until 12 h after the epidural injection. Peak plasma
      concentrations [mean (SD)] were 9.7 (2.3)ng.ml-1, and were attained in a median
      (range) time of 90 (30-120) min. The results suggest that alfentanil is slowly
      absorbed from the epidural space into the general circulation.

PMID- 7802178
TI  - Dexmedetomidine as intramuscular premedication for day-case cataract surgery. A
      comparative study of dexmedetomidine, midazolam and placebo.
AB  - The effects of dexmedetomidine 1.0 microgram.kg-1, midazolam 20 micrograms.kg-1
      and saline placebo were assessed in a double-blind, randomised study in 90
      patients undergoing day-case cataract surgery under regional anaesthesia. The
      trial drug was injected into the deltoid muscle 45 min before the peri-ocular
      block. Dexmedetomidine 1.0 microgram.kg-1 decreased intra-ocular pressure before,
      during and after surgery. The maximum reduction in mean (SD) intra-ocular
      pressure occurred in the dexmedetomine group just before discharge from hospital
      (17.7 (2.8) mmHg to 11.5 (2.9) mmHg) (p < 0.001 compared with midazolam and
      placebo). In contrast, midazolam did not differ from saline placebo.
      Dexmedetomidine and midazolam produced a similar sedative effect of short
      duration. Dexmedetomidine induced a moderate decrease in blood pressure (p <
      0.001 compared with placebo) and a slight but statistically significant decrease
      in heart rate throughout the study period (p < 0.001 compared with placebo).
      Dexmedetomidine 1.0 microgram.kg-1 intramuscularly, effectively reduced intra
      ocular pressure and produced short-acting sedation with marginal cardiovascular
      effects; it may be a useful premedicant drug for elderly patients undergoing day
      case cataract surgery under regional anaesthesia.

PMID- 7802179
TI  - A comparison of 25 G and 27 G Whitacre needles for caesarean section.
AB  - Spinal needles with a pencil-point tip and those of a finer gauge are known to be
      associated with a lower incidence of postdural puncture headache. This study set
      out to determine if fine pencil-point needles were acceptably easy to use in
      routine clinical practice. Two hundred and twelve women undergoing elective
      Caesarean section were randomly allocated to receive a subarachnoid block using
      either a 25 G or 27 G Whitacre needle. Factors determining ease of needle use,
      adequacy of block, incidence of postdural puncture headache, backache and
      neurological sequelae were assessed. Successful intrathecal injection was
      achieved in all patients in the 25 G group. Using the 27 G needle, the
      anaesthetist failed to reach the subarachnoid space in eight patients of which
      seven subsequently had a successful intrathecal injection with a larger needle.
      These failures were attributed to excessive needle flexibility which was the only
      significant difference in ease of use between the 25 G and 27 G needles. In the
      25 G group, there was one severe postdural puncture headache which required an
      epidural blood patch and three mild headaches which resolved spontaneously. There
      were no postdural puncture headaches in the 27 G group. We conclude that the
      final choice of needle is a compromise between the ease of use and lower failure
      rate of the 25 G needle and the, as yet unproven, possibility of a lower
      incidence of postdural puncture headache with the 27 G needle.

PMID- 7802180
TI  - The oesophageal detector device. An assessment of accuracy and ease of use by
      paramedics.
AB  - Accuracy, ease and speed of recognition of tracheal tube position were assessed
      using the oesophageal detector device in a series of 40 tests on 29 patients. A
      single blind method was used, with each paramedic performing a single test on
      each patient. The tests were randomly split between two groups consisting of
      those tests performed on the tracheal or oesophageal tube respectively. Of the 40
      tests performed, 21 were on tracheal tubes and 19 on oesophageal tubes. Correct
      placement was diagnosed with 100% accuracy by the paramedics, none of whom had
      previously used the oesophageal detector device. Each paramedic also graded speed
      of recognition of position and ease of use of the device. Recognition of position
      was graded as instant in 37 out of 40 tests. Use of the oesophageal detector
      device by previously inexperienced paramedics has thus been shown to be accurate,
      rapid and easy to learn.

PMID- 7802181
TI  - An impaled neck. Management of difficult airway access.
AB  - We describe the management of a patient impaled through the lower submandibular
      area by the top spike of some iron railings which immobilised his jaw and blocked
      access to the trachea. The Fire Brigade used specialised equipment to cut out a
      section of the railings so that the patient could be transported to hospital.
      Awake fibreoptic intubation was used to gain access to the patient's airway
      before induction of anaesthesia.

PMID- 7802182
TI  - Myocardial infarction in a parturient. A case report with emphasis on medication
      and management.
AB  - Myocardial infarction is rare in pregnancy. We report a 38-year-old woman with a
      history of smoking and pre-eclampsia in her previous pregnancy, who suffered a
      non-Q infarction at 18 weeks of gestation. Stenoses in the left coronary artery
      were verified angiographically. She delivered a healthy child vaginally under
      epidural anaesthesia.

PMID- 7802183
TI  - A rare and fatal complication of oesophagoscopy. Anaesthetic implications.
AB  - A 3.5-year-old child developed a tight oesophageal stricture following ingestion
      of caustic soda. At the end of the fourth anaesthetic for oesophageal dilatation,
      laryngospasm and difficulty in mask ventilation was followed by cyanosis,
      bradycardia, and cardiac arrest. Chest X ray showed a large pneumopericardium,
      which was immediately aspirated, but unfortunately resuscitation was
      unsuccessful. It was presumed that during attempted manual ventilation of the
      lungs in the presence of a closed glottis, air had been accidentally forced into
      the pericardium through a small tear in the fragile oesophagus.

PMID- 7802184
TI  - Inhalation anaesthesia and the Kearns-Sayre syndrome.
AB  - Kearns-Sayre syndrome is an extremely rare mitochondrial myopathy, characterised
      by retinitis pigmentosa associated with progressive external ophthalmoplegia.
      Cardiac conduction abnormalities are common and range from bundle branch block to
      third degree atrioventricular block. Generalised degeneration of the central
      nervous system has also been reported. We describe the anaesthetic management of
      a child afflicted by this syndrome. The major anaesthetic complication in this
      disease is sudden third degree atrioventricular block which may lead to death in
      the absence of an artificial cardiac pacemaker.

PMID- 7802185
TI  - Respiratory complications due to inadequate analgesia following thoracotomy in a
      neonate.
AB  - We present a case in which a 2-day-old infant suffered respiratory complications
      shortly following premature termination of a postoperative extradural infusion.
      Restoration of analgesia led to a marked clinical improvement.

PMID- 7802186
TI  - Differential lung ventilation as an alternative to one-lung ventilation during
      thoracotomy. Report of three cases.
AB  - Investigation was carried out on three elderly patients undergoing thoracotomy.
      During one-lung ventilation using a Robertshaw double-lumen tube, the PaO2
      decreased below 11.7 kPa despite ventilation of the dependent lung with 100%
      oxygen. Differential lung ventilation was then initiated by partial occlusion of
      the adapter limb to the nondependent lung, whilst maintaining unrestricted
      ventilation of the dependent lung. In the three patients, differential lung
      ventilation increased the PaO2 to 15-37.2 kPa. The increased PaO2 may be
      attributed to diffusion oxygenation via the partially inflated, nondependent
      lung. Differential lung ventilation can be used during thoracotomy whenever one
      lung ventilation is followed by hypoxaemia, despite adequate ventilation of the
      dependent lung with 100% oxygen.

PMID- 7802187
TI  - Mediastinitis and sepsis syndrome following intubation.
AB  - A patient developed sepsis syndrome with shock 7 h after an anaesthetic for a
      shoulder replacement. Tracheal intubation had been difficult and required the use
      of a stylet and gum-elastic bougies. A gastrografin swallow subsequently
      demonstrated an oesophageal perforation and mediastinitis was diagnosed at
      surgical exploration. She survived after a prolonged period of intensive care
      treatment.

PMID- 7802188
TI  - The need for quality control in measurement of mixed venous oxygen saturation.
AB  - We investigated the variability of arterial, mixed venous and peripheral venous
      oxygen saturation readings in three co-oximeters in regular use on two Intensive
      Care Units. Over a 2-week period, 96 readings were obtained from each of the
      following machines; two AVL 912 co-oxylite co-oximeters (Machines A and B,
      Biomedical Instruments, Graz, Austria) and one IL-282 (Machine C, Instrumentation
      Laboratories, Lexington, MA, USA). The coefficient of variation in the arterial
      oxygen saturations was extremely small on all three machines (< 0.43%). The
      coefficient of variation in the mixed venous samples, however, ranged from 1.96
      to 4.61% on machine A, and from 2.73 to 4.71% on machine B, but only from 0.17 to
      1.47% on machine C. The variation in mixed venous saturations obtained from a
      single blood sample repeatedly analysed on machines A and B was large enough to
      influence clinical management.

PMID- 7802189
TI  - The SMART needle. A new Doppler ultrasound-guided vascular access needle.
AB  - Central venous access is an essential part of patient management in many clinical
      settings. Traditionally this has been achieved by a blind, external landmark
      guided technique which may not correlate exactly with the location of the vessel.
      We have prospectively evaluated the SMART needle, a new Doppler ultrasound guided
      vascular access device, in 40 patients, to evaluate whether it can improve on the
      standard technique. The SMART needle was easy to use and reliably distinguished
      between arterial and venous signals. No advantage was demonstrated in 'easy'
      internal jugular vein cannulations. Although ease of cannulation in difficult
      cases was subjectively improved, the differences in time to cannulation and
      number of passes between the groups failed to reach statistical significance and
      the complication rates were similar. However, the use of the SMART needle on two
      occasions enabled avoidance of carotid artery puncture by correctly
      distinguishing the artery from the vein, so that it may have a role in patients
      in whom difficult internal jugular venous cannulation is anticipated.

PMID- 7802190
TI  - Can a drawover vaporizer be a pushover?
AB  - Bench testing was carried out to establish whether the vapour output from an
      OMV50 vaporizer, as used in the Triservice apparatus, differs according to
      whether the carrier gas is either drawn or pushed through the vaporizer. Results
      show that the differences in output concentration between the two modes were
      clinically insignificant.

PMID- 7802191
TI  - Blood pressure measurement using oscillometric finger cuffs in children and young
      adults. A comparison with arm cuffs during general anaesthesia.
AB  - Arterial blood pressure measurements (y) obtained from forefinger cuffs were
      compared with standard arm cuff readings (x) in 41 anaesthetised children and
      young adults. Mean (SD) differences between cuff measurements were -0.21 (9.15), 
      1.56 (10.2) and 1.23 (9.12) mmHg for the systolic, mean and diastolic pressures
      respectively. The correlation for systolic blood pressures (r = 0.85, y = 0.99x +
      0.58, sy.x = 9.15) was better than that for mean or diastolic pressures.
      Oscillometric finger cuffs are suitable for monitoring the systolic blood
      pressure in children and young adults during general anaesthesia.

PMID- 7802192
TI  - Emergency airway management in patients with cervical spine injuries.
AB  - A retrospective study of admissions to a Level 1 Trauma Centre, revealed 393
      patients with traumatic cervical spine injuries. All 36 patients intubated
      urgently and 37 and 68 patients intubated between 30 min and 24 h of admission,
      were intubated orally, following a rapid sequence induction with the application
      of cricoid pressure and manual in-line stabilisation of the head and neck. There
      were no neurological sequelae in these 73 patients (95% confidence interval 0
      4%). This technique for airway management is described in detail. It is a safe,
      familiar, and effective method for securing the airway in patients with cervical
      spine injury.

PMID- 7802193
TI  - Validation of a croup score and its use in triaging children with croup.
AB  - The Syracuse croup scoring system was validated in 165 children with croup who
      were admitted to an intensive therapy unit for assessment over a one year period.
      The unit served as a croup triage point for Cardiff and its environs. A score of
      > 5 was taken as an indication that a patient was at risk of upper airway
      obstruction and was used to support a triage decision by the junior hospital
      doctor to admit a patient to the intensive therapy unit. All patients with an
      initial score < or = 5 were considered safe for transfer to a general paediatric
      ward and none of these required subsequent admission to intensive care. This
      score was then tested on a further 134 children with croup, in order to identify
      those patients who required specialised monitoring, observation or treatment in
      intensive care. A score of > 5 gave a specificity of 100% and a sensitivity of
      80%. Croup scoring continued after admission on the general paediatric wards. Two
      patients who were originally admitted to the intensive therapy unit with a score
      > 5 improved within 6 h and were transferred to the general ward with a score <
      or = 5. These children subsequently required readmission to the intensive therapy
      unit. Our tracheal intubation rate of 2% was low and may relate to the routine
      use of regular adrenaline nebulisation. We recommend this scoring system to other
      paediatric departments for initial triaging decisions and for documenting
      progress on the wards.

PMID- 7802194
TI  - The effect of hyaluronidase on peribulbar block.
AB  - The effect of supplementing a standardised local anaesthetic mixture with
      hyaluronidase was studied in 60 patients undergoing peribulbar block for intra
      ocular surgery. All the patients had the block performed with a 2:1 mixture of
      lignocaine 2% and bupivacaine 0.75%, but in half of the cases hyaluronidase 50
      u.ml-1 was added to the solution by random allocation. The mean volumes of
      solution injected were 8.9 and 9.0 ml in the control and hyaluronidase groups
      respectively. Five minutes after injection the block was deemed unsuccessful in
      one third of the patients in each group and these patients required supplementary
      injections. At 15 min all but one patient in each group had satisfactory block
      and these two patients subsequently required retrobulbar block. There were no
      statistically significant differences between the two solutions in rate of onset
      of block, requirement for supplementation, block failure, or surgical conditions.
      There were no significant complications. We conclude that the addition of
      hyaluronidase 50 u.ml-1 to the local anaesthetic mixture described confers no
      advantage at the volumes of local anaesthetic used.

PMID- 7802195
TI  - Acid aspiration prophylaxis in elective biliary surgery. A comparison of
      omeprazole and famotidine using manually aided gastric aspiration.
AB  - We have compared the effects of single oral doses of omeprazole 40 mg, famotidine
      40 mg or placebo on gastric secretion in 45 non-obese patients the night before
      elective biliary surgery. After stable anaesthesia had been established, a Salem
      orogastric tube was introduced and gastric contents were aspirated by a blinded
      observer. The volume and pH were noted. After the abdomen was opened aspiration
      was repeated but on this occasion with the surgeon's manual assistance. We found
      that the initial aspirate volume underestimated total gastric volume by an
      average (SD) of 7.1 (6.6) ml. Famotidine, but not omeprazole, produced a
      significant decrease in gastric volume and acidity. Patients were considered to
      be at risk if pH < 2.5 and volume > 0.4 ml.kg-1. Three patients in the omeprazole
      group, three in the placebo group and none in the famotidine group came into this
      category. We conclude that a single oral dose of omeprazole 40 mg given the night
      before surgery does not afford adequate prophylaxis for acid aspiration syndrome.

PMID- 7802196
TI  - Peri-operative effect of major gastrointestinal surgery on serum magnesium.
AB  - This study investigates the changes in serum magnesium levels after major
      gastrointestinal surgery and evaluates if Plasma-Lyte 148 used as maintenance
      fluid influences these changes in the peri-operative period. Thirty patients
      presenting for procedures ranging from anterior rectal resection to thoraco
      abdominal cardio-oesophagectomy were randomly allocated into two groups, one of
      which received compound sodium lactate solution as the maintenance crystalloid
      during the intra- and postoperative period, and the other Plasma-Lyte 148, a
      magnesium-containing crystalloid solution. Serum magnesium levels were measured
      pre-operatively, in the immediate recovery period and 24 h postoperatively. The
      results showed a statistically significant (p < 0.05) reduction in the magnesium
      levels in both groups. The reduction was less marked in the Plasma-Lyte group but
      this did not achieve statistical significance (p > 0.05) compared with the
      compound sodium lactate group.

PMID- 7802197
TI  - Puncture of the laryngeal mask airway cuff.

PMID- 7802198
TI  - A new simple device for fixing orotracheal tubes.

PMID- 7802199
TI  - Bronchospasm and the laryngeal mask airway.

PMID- 7802200
TI  - Incorrect settings on Manley ventilators.

PMID- 7802201
TI  - Smoking reduction and tape suggestion.

PMID- 7802202
TI  - Hazard of reinforced tracheal tubes.

PMID- 7802203
TI  - Hazard of reinforced tracheal tubes.

PMID- 7802204
TI  - Forestier's disease (ankylosing hyperostosis): a cause for difficult intubation.

PMID- 7802205
TI  - A complication of tracheal intubation?

PMID- 7802206
TI  - Awake versus asleep fibreoptic intubation.

PMID- 7802207
TI  - Sterilisation of gum elastic bougies.

PMID- 7802208
TI  - Lingual haematoma following streptokinase therapy.

PMID- 7802210
TI  - Apparent resistance to thiopentone--a continuing problem.

PMID- 7802209
TI  - Portable suction devices.

PMID- 7802211
TI  - Evidence of the cause of Baxter PCA balloon rupture.

PMID- 7802212
TI  - Phantom limb pain and spinal anaesthesia.

PMID- 7802213
TI  - A complication of inappropriate use of peripheral nerve stimulation.

PMID- 7802214
TI  - Necrosis of the uvula.

PMID- 7802215
TI  - The value of battery back-up.

PMID- 7802216
TI  - Another latex allergy.

PMID- 7802217
TI  - Asystole associated with mivacurium.

PMID- 7802218
TI  - Pulse oximetry: incorrect use leading to failure to fail safe.

PMID- 7802220
TI  - Research and publication as a component of the curriculum vitae.

PMID- 7802219
TI  - Single medial injection peribulbar anaesthesia using prilocaine.
AB  - A prospective randomised study is reported comparing a single peribulbar
      injection into the medial compartment of the orbit and the standard two injection
      peribulbar technique. One hundred and seven patients undergoing elective intra
      ocular surgery were randomly allocated to receive either a single medial
      injection, or two injections, using prilocaine 3% with felypressin. Akinesia and
      pain during surgery were assessed following the injection(s). There was no
      significant difference in pain during surgery and globe akinesia between the two
      groups. The single medial peribulbar injection is as effective as two injections
      using prilocaine 3%.

PMID- 7802221
TI  - International interhospital transfer.

PMID- 7802222
TI  - Patients' assessment of height and weight.

PMID- 7802223
TI  - Barotrauma and the laryngeal mask airway.

PMID- 7802224
TI  - The laryngeal mask for laser surgery to the pharynx.

PMID- 7802225
TI  - Pre-operative anxiety--a single blind 'crossover' study.

PMID- 7802226
TI  - Assessment of EMOX 911.

PMID- 7802227
TI  - More problems with gas sampling tubes.

PMID- 7802228
TI  - Manganese toxicity in a patient with cholestasis receiving total parenteral
      nutrition.

PMID- 7802229
TI  - Fatal respiratory obstruction following insertion of a central venous line.

PMID- 7802230
TI  - An experience with the Sprotte needle.

PMID- 7802231
TI  - Nonbronchoscopic broncho-alveolar lavage in a neonate.

PMID- 7802232
TI  - Pain scores during venous cannulation.

PMID- 7802233
TI  - Paying the piper--calling the tune?

PMID- 7802234
TI  - Survival after intensive care. Comparison with a matched normal population as an
      indicator of effectiveness.
AB  - The life expectancy for survivors of critical illness has not been reported in
      the United Kingdom. The aim of this study was to compare the long-term survival
      of intensive care patients with that of an age and sex-matched population. All
      patients admitted to a general intensive therapy unit over 4 years (n = 1168)
      were included in the study. Details of the survivors were forwarded to the
      Registrar General for Scotland, who then issued copies of death certificates as
      the survivors died. The survival curve of patients discharged from the intensive
      therapy unit was significantly different from that of the normal population. The
      risk of dying in the first year after discharge was 3.4 times higher (95%
      confidence intervals 2.7-4.2) than that in the normal population. It is not until
      the start of the fourth year after discharge that the probability of death
      matched that of the normal population.

PMID- 7802235
TI  - Circulating fluoride changes and hepatorenal function following sevoflurane
      anaesthesia.
AB  - Sevoflurane, a new volatile inhalational agent, undergoes biotransformation to
      fluoride which is potentially nephrotoxic. We compared the effects of sevoflurane
      or isoflurane anaesthesia on hepatorenal function and serum fluoride
      concentrations in 50 ASA 1-3 patients undergoing major intra-abdominal surgery.
      No patient developed renal or hepatic dysfunction. Mean (SEM) peak fluoride
      concentrations were 23.1 (1.5) mumol.l-1 for sevoflurane and 5.4 (0.4) mumol.l-1
      for isoflurane (p < 0.001). There was a significant correlation in the
      sevoflurane group between the total dose of agent (MAC h), the total fluoride
      production (r = 0.78, p = 0.0001) and peak fluoride concentration (r = 0.57, p =
      0.003). There was no correlation between these variables in the isoflurane group.

PMID- 7802236
TI  - Administration of rocuronium (Org 9426) by continuous infusion and its
      reversibility with anticholinesterases.
AB  - The use of rocuronium (Org 9426) as a single bolus followed by an infusion was
      assessed in 50 patients under anaesthesia with nitrous oxide-oxygen and
      halothane. Neuromuscular block was monitored using train-of-four stimulation and
      recording the force of contraction of the adductor pollicis muscle. Rocuronium
      was administered in an initial bolus dose of 0.45 mg.kg-1 followed by an infusion
      adjusted manually to maintain the T1, the first response in the train-of-four, at
      10% of control. Following cessation of rocuronium infusion the patients were
      either allowed to recover spontaneously (n = 10) or were given neostigmine 50
      micrograms.kg-1 or edrophonium 1 mg.kg-1 at 10 or 25% recovery of the T1 (n = 10
      for each group). Adequate antagonism was defined as attaining a sustained train
      of-four ratio of 0.7. Rocuronium requirements showed marked variation among
      individual patients but were relatively constant in individual patients. The mean
      (SD) time to attain stable infusion rates was 17.4 (10.9) min. The mean (SD)
      requirement of rocuronium for steady state 90% block of T1 was 572 (190)
      micrograms.kg-1.h-1 (range 242-1104 micrograms.kg-1.h-1). The mean (SD) time to
      attain a train-of-four ratio of 0.7 in the group allowed to recover spontaneously
      was 36.1 (7.3) min. This interval was 7.5 (1.9), 9.3 (7.0), 4.6 (1.9) and 1.9
      (0.9) min respectively in the groups receiving neostigmine at T1 of 10%,
      edrophonium at T1 of 10%, neostigmine at T1 of 25% and edrophonium at T1 of 25%.
      The antagonism was significantly faster in those reversed at 25% (p < 0.05).
      Three patients in the group receiving edrophonium at T1 of 10% and one in the
      group receiving neostigmine at T1 of 25% failed to attain a train-of-four ratio
      of 0.7. It is concluded that rocuronium can be administered as a continuous
      infusion for stable neuromuscular block. Neostigmine may be a more reliable
      antagonist of deep block, whereas edrophonium is advantageous when there is a
      greater spontaneous recovery.

PMID- 7802237
TI  - Recovery of mivacurium block with or without anticholinesterases following
      administration by continuous infusion.
AB  - Thirty patients received a bolus dose of 0.2 mg.kg-1 of mivacurium followed by an
      infusion during anaesthesia with thiopentone, fentanyl and halothane.
      Neuromuscular block was monitored using train-of-four stimulation and
      mechanomyography and the block maintained to keep the first response in the train
      of-four (T1) at 10% of control. At the end of surgery the patients were randomly
      allocated to reversal with neostigmine or edrophonium or to spontaneous recovery.
      The mean dosage of mivacurium for maintaining the T1 at 10% was 5.7 micrograms.kg
      1.min-1. There was a significant (r = -0.81, p < 0.001) negative correlation
      between time to recovery of T1 to 10% after the bolus dose and infusion rate. The
      times taken for T1 to reach 25, 75 and 90% of control and for the train-of-four
      ratio to reach 0.7 were significantly shorter (p < 0.05 to 0.001) with
      neostigmine and edrophonium compared to the spontaneously recovering group. The
      average (SD) times for attaining the train-of-four ratio of 0.7 were 7.0 (1.2),
      6.8 (1.4) and 13.5 (2.3) min respectively for neostigmine, edrophonium and
      spontaneously recovering groups. There were no differences between endrophonium
      and neostigmine in any of the recovery times.

PMID- 7802239
TI  - Spinal cord compression immediately following, but unrelated to, epidural
      analgesia.
AB  - A patient developed spinal cord compression following epidural analgesia. The
      diagnosis was made difficult by the presence of epidural analgesia, although the
      compression was not in fact related to the analgesic technique employed. This
      case highlights the need for close observation of patients in whom epidural
      analgesia is, or has recently been, employed and the need to consider alternative
      reasons for neurological deficit.

PMID- 7802238
TI  - Detection of cerebral hypoperfusion during cardiopulmonary bypass. Continuous
      measurement of cerebral venous oxyhaemoglobin saturation during myocardial
      revascularisation.
AB  - We measured continuously cerebral venous oxyhaemoglobin saturation (SjvO2) using
      a 4F fibreoptic catheter in 11 patients scheduled for elective myocardial
      revascularisation. The aims of this study were to assess the Oximetrix 3 computer
      and Opticath 40 cm catheter during moderate hypothermic cardiopulmonary bypass,
      and identify epochs of cerebral hypoperfusion (SjvO2 < 54%). Radial artery
      pressure, brain electrical activity, arterial and cerebral venous oximetry (dual
      oximetry), end-tidal CO2 and nasopharyngeal temperature were recorded
      continuously in each patient. Following in vivo calibration of 11 continuous
      SjvO2 catheters and monitor, 57 simultaneous, paired recordings were additionally
      taken. The mean difference between the catheter SjvO2 and the in vitro laboratory
      derived value was 0.34%, with a 95% confidence interval -3.2% to 2.4%. In 10
      patients SjvO2 decreased below normal at rewarming and myocardial reperfusion:
      mean lowest value 37%, range 19%-55%. Reduced SjvO2 were associated with a
      decrease in perfusion pressure (r = 0.292, 80 DF, p = 7.7* 10(-3)), and with an
      increase in nasopharyngeal temperature (r = -0.46, 115 DF, p = 2.7* 10(-7)) after
      moderate hypothermia. The Oximetrix 3 computer and Opticath 40 cm catheter
      provided reliable and accurate continuous monitoring of SjvO2 during nonpulsatile
      cardiopulmonary bypass involving hypothermia with haemodilution and identified
      rewarming as the period of greatest risk of global cerebral hypoperfusion.

PMID- 7802240
TI  - Elevated porphyrins following propofol anaesthesia in acute intermittent
      porphyria.
AB  - A patient with acute intermittent porphyria was anaesthetised with propofol for a
      minor orthopaedic procedure. Postoperative urinary porphyrins were markedly
      raised compared to pre-operative values, although the patient remained clinically
      well. Caution should continue to be exercised when propofol is used in patients
      with acute porphyrias.

PMID- 7802241
TI  - Phakomorphic glaucoma--an unusual cause of postoperative vomiting.
AB  - A 60-year-old female patient receiving epidural buprenorphine for postoperative
      analgesia developed intractable nausea and vomiting not responding to
      antiemetics. Ophthalmic consultation for congestion of the left eye was sought
      and the patient was diagnosed as having phakomorphic glaucoma. Extracapsular
      extraction of the left lens was performed after primary anti-oedema measures.
      Glaucoma as a cause of intractable postoperative nausea and vomiting should be
      considered in susceptible patients.

PMID- 7802242
TI  - Haemothorax after attempted intercostal catheterisation.
AB  - A 30-year-old man with chronic abdominal pain was referred to the Pain Relief
      Unit after a course of unsuccessful diagnostic blocks and treatments. On
      admission, history, examination and clinical investigations were consistent with
      a large pleural effusion due to a recent attempt to catheterise the intercostal
      space. Pleural drainage confirmed the diagnosis of haemothorax. Percutaneous
      intercostal nerve blocks are usually considered as safe and simple and no-one to
      our knowledge has reported such a complication.

PMID- 7802243
TI  - Ethylene glycol antifreeze poisoning. Three case reports and a review of
      treatment.
AB  - We present three patients with ethylene glycol antifreeze poisoning whose
      management included the use of continuous veno-venous haemodiafiltration. Results
      from these cases demonstrate clearance of the ethylene glycol molecule.

PMID- 7802244
TI  - A comparison of arterial lines and insertion techniques in critically ill
      patients.
AB  - We compared three arterial line insertion techniques and two types of arterial
      catheters in 69 critically ill patients. Use of the direct-puncture technique
      (method A) was associated with a significantly higher failure rate (23%) than use
      of a catheter with a separate guide wire (method B, 'classical' Seldinger
      technique, p < 0.001) or a catheter with an integral guide wire (method C,
      'modified' Seldinger technique, p < 0.02). Operators randomly allocated to using
      method A took significantly longer to perform the procedure than those using
      method C (p < 0.01), used significantly more catheters (p < 0.0001) and made
      significantly more punctures in achieving a successful insertion than those using
      either methods B (p < 0.001) or C (p < 0.001). Both catheter types B and C
      (polyurethane) were significantly less likely to block, thus requiring less
      likely to block, thus requiring re-insertion, than catheter type A (Teflon) (p <
      0.02, p < 0.01 respectively). We recommend the use of a 'classical' Seldinger
      technique (method B) for arterial line insertion in critically ill patients and
      the use of a polyurethane catheter, in preference to Teflon, to maximise catheter
      life after insertion.

PMID- 7802245
TI  - A multilumen catheter guide for difficult airway management. Its uses in
      anaesthesia and intensive care.
AB  - A multilumen catheter guide (jet stylet) with an adapter has been used for
      various manoeuvres in the upper airway. With the split length, procedures such as
      change of tracheal tube from oral to nasal nasal to oral position, are possible
      while the patient's lungs are ventilated by means of high frequency jet
      ventilation. During high frequency jet ventilation for longer periods of time,
      for example for microlaryngeal surgery, the central channel of the catheter is
      used as a conduit for jet delivery, whilst the other channels are used for
      continuous monitoring of airway pressure and concentration of carbon dioxide in
      the upper airway.

PMID- 7802246
TI  - The polyurethane nasotracheal tube.
AB  - An uncuffed nasotracheal tube for use in minor maxillofacial surgery has been
      developed using polyurethane. The suitability of this tube as an alternative to
      the existing soft red rubber and harder polyvinyl chloride materials has been
      assessed at four centres during anaesthesia for routine oral surgery. The tube
      was found to be satisfactory.

PMID- 7802247
TI  - Noise pollution in the anaesthetic and intensive care environment.
AB  - Noise in the operating theatre, recovery room and intensive care unit is above
      internationally recommended levels. The psychological and physiological effects
      of noise are reviewed. Equipment and conversation among the staff are major
      sources of noise in these areas. Equipment design, modification of nursing care
      procedures, and increased awareness of noise created by the staff may be
      effective in reducing noise pollution in these areas.

PMID- 7802248
TI  - Parents in the anaesthetic room--parents' and anaesthetists' views.
AB  - In this study parents' and anaesthetists' views were compared, by means of
      questionnaire, to assess the benefit of parental presence at induction. One
      hundred and ninety four unpremedicated children aged 1-16 years underwent daycase
      surgery. One hundred and eighty four parents accompanied their child and felt
      that their child benefited from this. Anaesthetists rated only 72% of parents as
      being helpful. Parents who had undergone anaesthesia in the past were less
      likely, 60% compared with 79% (p < 0.01), to consider themselves as upset than
      parents who had not. Thirty one percent (44/140) of anaesthetists, compared with
      43% (60/140) of parents, felt the child was upset at induction (p < 0.01).
      Parents judging themselves to be upset at induction were significantly more
      likely to consider their child as upset (p < 0.01). Most parents feel that they
      are of help in the anaesthetic room regardless of whether or not they find it an
      upsetting experience. Ninety eight per cent would want to accompany their child
      in the future and we believe this should be allowed unless there are overriding
      considerations.

PMID- 7802249
TI  - Factors important in determining trainee anaesthetists' quality of life.
AB  - A postal survey of all trainee anaesthetists in the North West Region of England
      was conducted to investigate areas important in determining the trainee's quality
      of life. The questionnaire enquired about life on-call, hospital facilities
      available to doctors and trainees' morale. The results suggest that changes are
      urgently required to improve trainees' lifestyles and therefore help raise morale
      within the profession.

PMID- 7802250
TI  - A comparison of thiopentone and propofol with respect to the incidence of
      postoperative shivering.
AB  - One hundred patients (69 female) undergoing surgical excision of three or more
      wisdom teeth were randomly allocated to receive either thiopentone or propofol
      for induction of anaesthesia. Other than the induction agent, the anaesthetic
      regimen was standardised for all cases. All patients were observed for 15 min
      after entry into the recovery area to assess the presence and intensity of
      shivering. Twenty-five patients in the thiopentone group (n = 50) and 11 patients
      in the propofol group shivered postoperatively (p < 0.005). There was no
      statistically significant difference in axillary temperature between shivering
      and non-shivering patients. The use of propofol as an induction agent is
      associated with a lower incidence of postoperative shivering than thiopentone.

PMID- 7802251
TI  - The effect of clonidine on intra-operative requirements of fentanyl during
      combined epidural/general anaesthesia.
AB  - The study evaluates the analgesic effects of epidural clonidine in patients
      undergoing abdominal hysterectomy under combined epidural/general anaesthesia.
      Forty ASA 1-2 patients were divided into two groups who received epidurally
      either clonidine 300 micrograms (group 1) or placebo (group 2). Anaesthesia was
      maintained with oxygen/nitrous oxide, a midazolam infusion, vecuronium, and
      boluses of fentanyl 100 micrograms administered as needed to maintain
      cardiovascular stability. The mean (SD) intraoperative fentanyl requirements were
      2.05 (0.18) and 3.66 (0.3) micrograms.kg-1.h-1 for groups 1 and 2 respectively (p
      < 0.001). Patients in Group 1 had a lower heart rate after tracheal intubation
      and surgical incision (p < 0.02). In the recovery room, pain intensity was lower
      in group 1 (p < 0.003) and the mean (SD) time until analgesia request was
      increased from 48.5 (8.4) min in group 2 to 235.7 (33.2) min in group 1 (p <
      0.001). Our results demonstrate that epidural clonidine produces decreased
      fentanyl requirements, improved cardiovascular stability, reduced pain intensity
      and effective postoperative analgesia in the recovery room.

PMID- 7802252
TI  - Cyclic polyamine ionophore for use in a dibasic phosphate-selective electrode.
AB  - A cyclic polyamine, 3-decyl-1,5,8-triazacyclodecane-2,4-dione (N3-cyclic amine),
      was used as the ionophore for a dibasic phosphate-selective electrode. This
      electrode exhibited a linear response between 1.0 mumol/L and 0.1 mol/L dibasic
      phosphate activity with a near-Nernstian slope of approximately -29 mV per
      activity decade. The electrode selectivity for dibasic phosphate over other
      commonly occurring anions was evaluated. A mechanism for the selectivity of the
      electrode toward HOP4(2-) ions is postulated to be a function of the size and
      charge of the N3-cyclic amine ionophore relative to the size and charge of HPO4(2
      ) ions. The electrode's superior selectivity and sensitivity make possible the
      direct measurement of phosphate activity in a wide variety of applications.

PMID- 7802253
TI  - Determination of total chromium in whole blood, blood components, bone, and urine
      by fast furnace program electrothermal atomization AAS and using neither analyte
      isoformation nor background correction.
AB  - Fast furnace program (total furnace time < 45 s) electrothermal atomization
      atomic absorption spectrometric (ETA-AAS) determinations of total Cr in several
      clinical materials were carried out in conventional (DABC) and transverse (ZEBC)
      heated graphite atomizers. Before spectrometric determination, test portions of
      the samples were diluted at different ratios in appropriate solvents: (a) whole
      blood (WB), blood plasma (BP), blood serum (BS), and red blood cells (RBC), 1 + 4
      in 0.1% (v/v) Triton X-100; (b) urine (U), 1 + 4 in 0.1% (v/v) Triton X-100 +
      0.01 mol/L nitric acid; and (c) bone (B) specimens and the certified reference
      materials after microwave mineralization, 1 + 9 in 0.01 mol/L nitric acid. The
      refractoriness of Cr allowed pyrolysis at a high temperature (approximately 1650
      degrees C). As a consequence, two facts arose: first, isoformation was
      unnecessary; and second, background correction, independent of use of continuum
      source (DABC design) or Zeeman effect (ZEBC design) correction, was not required.
      For these reasons, the fast furnace program ETA-AAS analyses were simply done by
      automatic injection of 10-microL aliquots of the diluted test portions (or
      aqueous Cr standards) into either pyrolytic graphite-coated graphite tubes (DABC
      design; wall atomization performed) or pyrolytic graphite-coated graphite tubes
      with integrated pyrolytic graphite platforms (ZEBC design; integrated platform
      atomization performed), using neither analyte isoformation nor background
      correction; wall atomization in coated tubes was preferred. Under these
      experimental conditions, the limits of detection (3 sigma, micrograms/L Cr) and
      the characteristic masses (pg of Cr) were 0.03 and 2.7 (DABC design) and 0.2 and
      5.0 (ZEBC design), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7802254
TI  - Universal spectropolarimeter based on overtone circular dichroism measurements in
      the near-infrared region.
AB  - A novel and highly sensitive circular dichroism spectropolarimeter for the near
      infrared region has been developed. In this instrument, a solid state titanium
      sapphire laser that can be spectrally tuned from 670 to 1030 nm was used as the
      light source. The laser beam was converted into linearly polarized light by a
      polarizer and into left circularly polarized light and right circularly polarized
      light at 42 kHz by a photoelastic modulator (PEM). A limit of detection of 1.1 x
      10(-6) AU was achieved by this instrument for (+)-Co(en)3(3+) at 765 nm. Further
      improvement including employing double modulation (at 42 kHz by the PEM and at 85
      Hz by a chopper just before the laser beam was converted to CPL), demodulating
      and amplifying the signal with high-performance lock-in amplifiers, was made to
      enable the instrument to have the required sensitivity for the measurements of
      the circular dichroism of overtones and combination transitions of saturated
      chiral compounds, e.g., (R)- and (S)-camphor, (R)- and (S)-2-octanol, and (R)-
      and (S)-2-amino-1-octanol. Because the measured CD spectra originate from the
      overtones and combination transitions of the C-H and O-H groups, the
      spectropolarimeter can be used to detect virtually any compounds that have O-H
      and/or C-H groups.

PMID- 7802255
TI  - Determination of beta-lactam residues in milk using perfusive-particle liquid
      chromatography combined with ultrasonic nebulization electrospray mass
      spectrometry.
AB  - The introduced electrospray (ESP) technique combined with quadrupole mass
      spectrometry (MS) was applied for the trace residue detection (10 ppb) of
      commonly administered beta-lactam antibiotics in bovine milk. Because of the
      widespread use of penicillin G, ampicillin, amoxicillin, cephapirin, cloxacillin,
      and ceftiofur in veterinary medicine, these six popular drugs were chosen to
      develop a fast and reliable microcolumn liquid chromatographic (micro-LC)
      separation method for residue-containing milk extracts. Furthermore, the analytes
      were selected to test the chromatographic behavior of a novel stationary phase, a
      perfusive-particle column packed with derivatized porous polystyrene
      divinylbenzene. The effects of mobile phase additives on separation and ESP
      ionization efficiency were investigated. The ionization of the eluted analytes
      took place either in a conventional ESP interface with a capillary shield
      allowing flow rates up to 40 microL/min or in the latest model of the ultrasonic
      nebulization ESP interface. The perfusive-particle column, although not optimized
      for the separation of small molecules, exhibited sufficient resolution of the
      antibiotics for its routine usage, especially when considering the remarkable
      time-saving advantage compared with ordinary reversed phase micro-LC columns. The
      application of the novel ultrasonic nebulization interface lowered detection
      limits and improved the stability of the signals over a much wider flow rate
      range than possible for ionization with the ESP system equipped with the
      conventional needle.

PMID- 7802256
TI  - LC/ESI-MS determination of proteins using conventional liquid chromatography and
      ultrasonically assisted electrospray.
AB  - Conventional unassisted electrospray ionization mass spectrometry (ESI-MS) has
      severe limitations as a liquid chromatography (LC) interface due to the few
      solvent compositions which can be electrosprayed without some type of assistance.
      LC mobile phases which have high flow rates (over 5 microL/min), high
      conductivity, or high surface tension are normally unsuitable for use with ESI.
      For this reason, an ultrasonic nebulizer has been developed which mechanically
      creates the fine spray of droplets needed for ESI and thus functions
      independently of the solvent composition. This device also operates at
      considerably higher liquid flow rates, up to several hundred microliters per
      minute. To characterize the system's performance, the ultrasonic nebulizer
      frequency, source electrode potentials, and drying and focusing gas flow rates
      were studied and optimized. Also, droplet size measurements were taken using a
      phase-Doppler anemometer, which showed consistent nebulizer performance up to a
      liquid flow rate of several hundred microliters per minute. Finally, the
      ultrasonic nebulizer was used for an LC application involving the separation of
      proteins on 1.0 and 2.1 mm i.d. columns. LC flow rates of up to 200 microL/min of
      mobile phases containing 0.1% trifluoroacetic acid could be easily nebulized.
      With the 1.0 mm i.d. column, as little as 32 fmol of cytochrome c could be
      detected in selected ion monitoring mode.

PMID- 7802257
TI  - Prompt fragmentation of disulfide-linked peptides during matrix-assisted laser
      desorption ionization mass spectrometry.
AB  - During the analysis of an Asp-N digest of a recombinant hematopoietic growth
      factor by matrix-assisted laser desorption ionization mass spectrometry (MALDI
      MS), we observed pseudomolecular ions corresponding to reduced forms of peptides
      known to be present only in single disulfide linkages. Chromatographic
      fractionation of the peptide digest, followed by MALDI-MS and electrospray
      ionization (ESI) MS, confirmed that the reduced peptides were not present in the
      map. Fragmentation of the disulfide-linked peptides into their reduced forms
      occurred upon ionization from different matrices (alpha-cyano-4-hydroxycinnamic
      acid,2,5-dihydroxybenzoic acid, and in some instances sinapinic acid) but only
      after increasing the laser fluence to above threshold. Analysis of the disulfide
      linked peptide fractions by ESI-MS, before and after mixing and drying with
      matrix, indicated that the matrix did not cause reduction. In a low-energy tandem
      mass spectrometric experiment with one of the cystinyl peptides, fragmentation
      did not occur preferentially at the disulfide bond. The pseudomolecular ions
      exhibited the same m/z values by MALDI-MS as their chemically reduced
      counterparts, indicating that they arose due to prompt fragmentation or "in
      source decay" rather than "post-source decay". This finding is important for
      MALDI-MS analysis of peptide maps of proteins and peptide fractions with intact
      disulfides.

PMID- 7802258
TI  - Raman spectroscopic measurement of spatial and temporal temperature gradients in
      operating electrophoresis capillaries.
AB  - Steady-state and transient intracapillary temperature gradients are measured by
      Raman microthermometry during capillary zone electrophoresis. The axial
      temperature gradient away from a heat sink extends for several millimeters,
      depending upon the contact of the capillary and heat sink. In free-air
      convection, small radial gradients, 2-4 degrees C from the center of the lumen to
      the wall, are observed at 0.85 kW/cm3. The temperature profile is adequately
      described by a parabola. With forced cooling, the center-wall temperature
      difference is less than 1 degrees C. The time to steady-state temperature after
      power-on is found to be 20 s. The measurements are compared to the results of
      heat transport calculations.

PMID- 7802259
TI  - Predictive steady-state chromatography. 1. Algorithms for leading and trailing
      edges of resolved and unresolved peaks in liquid chromatography.
AB  - This paper describes mathematical models and curve-fitting procedures that permit
      steady-state saturation signals to be computed accurately from data along leading
      and trailing edges of liquid chromatograms. This new approach to quantitative
      chromatography is called predictive steady-state chromatography (PSSC). It is
      shown that the computed saturation signals are virtually the same when determined
      from data along leading and trailing edges and they vary linearly with analyte
      concentration. Most importantly, the computed saturation signals for a given
      analyte concentration are virtually independent of experimental variables such as
      sample volume and flow rate. For example, for sample volumes between 25 and 45
      microL, the average computed saturation signal for a 0.025 mM solution of
      theophylline was 0.11 V with a standard deviation of 0.00097 V (RSD = 0.8%);
      similar results were found for other concentrations and for changes in flow rate.
      Dependencies of the PSSC method on sample volume and flow rate were compared with
      dependencies for peak-height and peak-area methods by using relative error
      coefficients. Dependencies on sample volume were 0.04%/microL for the PSSC method
      and 3 and 4%/microL for peak-height and peak-area methods, respectively.
      Dependencies on flow rate were 2%/mL/min for the PSSC method and 17 and
      120%/mL/min for the peak-height and peak-area methods, respectively. Thus, the
      predictive steady-state method is 10-100-fold more rugged than peak-height and
      peak-area methods.

PMID- 7802261
TI  - Chiral separation mechanisms in protein-based HPLC columns. 1. Thermodynamic
      studies of (R)- and (S)-warfarin binding to immobilized human serum albumin.
AB  - This work characterizes the thermodynamic processes involved in the binding and
      separation of (R)- and (S)-warfarin on a high-performance human serum albumin
      (HSA) column. Frontal analysis was used to determine the strength and degree of
      binding for each enantiomer. (R)- and (S)-warfarin were found to bind at the same
      region on HSA; however, (R)-warfarin had a larger number of column binding sites.
      The number of binding sites for both enantiomers showed a slight increase with
      temperature. The total changes in free energy for (R)- and (S)-warfarin binding
      were similar at 37 degrees C, but the contribution due to entropy was greater for
      the R-enantiomer. These results suggested that (R)-warfarin was interacting
      mainly with the binding site interior, while (S)-warfarin interacted more with
      the site's outer surface. This model was confirmed by examining the retention of
      (R)- and (S)-warfarin on the HSA column under various pH, ionic strength, and
      organic modifier conditions. The different changes in entropy for these solutes
      made it possible to vary their separation by changing column temperature. Both
      thermodynamic properties and column binding capacities were found to be important
      in determining the degree of separation obtained for these compounds.

PMID- 7802260
TI  - Selectivity in electrophoretically mediated microanalysis by control of product
      detection time.
AB  - Differential electrophoretic mobility between an analyte and its product offers
      electrophoretically mediated microanalysis (EMMA) a unique capability to
      selectively control the detection time of the product of a reaction-based
      chemical analysis. If an analyte and its product differ in migration velocity
      under the influence of an applied electric field, the apparent velocity and,
      consequently, the detection time of the product are dependent upon the relative
      amounts of time the product effectively traverses the capillary with the
      respective mobilities of the analyte and the product. Consequently, by
      controlling when the analytical reaction is allowed to occur, the detection time
      of the reaction product can be selectively maneuvered within a time window
      defined by the mobilities of the analyte and the product. This paper describes
      the use of this technique to manipulate the detection time of product profiles
      independently of nonreacting matrix interferants for the determination of both
      enzymes and substrates by EMMA. Furthermore, the ability to manipulate product
      detection times allows for simultaneous EMMA determinations of multiple enzymes
      or substrates.

PMID- 7802262
TI  - Flow injection assay for the neurotoxin beta-ODAP using an immobilized glutamate
      oxidase reactor with prereactors to eliminate glutamate interferences.
AB  - The neurotoxic amino acid, beta-N-oxalyl-L-alpha,beta-diaminopropionic acid (beta
      ODAP,ODAP) was oxidized by immobilized glutamate oxidase (GlOD) to produce
      hydrogen peroxide. The peroxide reacts with Trinder reagent in a reactor with
      immobilized horseradish peroxidase to form a red-colored quinone imine dye, which
      was detected spectrophotometrically at 512 nm. Determinations were made in a flow
      injection (FI) setup consisting of four packed-bed enzyme reactors containing
      GlOD (20 microL), catalase (20 microL), GlOD (250 microL), and peroxidase (50
      microL) in series. Glutamate is oxidized quantitatively in the first reactor, but
      the hydrogen peroxide is destroyed in the second so that interferences from this
      substrate are removed. This step destroys only a few percent of the ODAP in the
      sample. Most of the remaining ODAP is oxidized in the third reactor. Injections
      of 20-microL ODAP standards gave a response curve which was linear within the
      range 10-650 microM. Phosphate buffer extracts of grass peas (lathyrus sativus)
      were purified by centrifugation and membrane filtration. Samples were injected
      into the FI setup to assay the toxin at a rate of 20 samples per hour. The beta
      ODAP content of a batch of dry seed corresponded to 0.74% (w/w) with a relative
      standard deviation of 2.8%. Thermal treatment of ODAP standards at 80-90 degrees
      C reduced the response to 62% of that before heating. The decrease is due to
      beta<-->alpha isomerization, and the experiment thus confirms that the method is
      selective for the toxic beta-isomer.

PMID- 7802264
TI  - Postoperative arterial oxygen saturation: what to expect.

PMID- 7802263
TI  - Engineering the maltose binding protein for reagentless fluorescence sensing.
AB  - This paper describes a mutant of the maltose binding protein (MBP) in which the
      serine residue at position 337 is replaced by a cysteine residue using site
      directed mutagenesis. The mutant MBP has an approximately 2-fold lower affinity
      for maltose, and the cysteine residue can be modified with 4-[N-(2
      (iodoacetoxy)ethyl)-N-methylamino]-7-nitrobenz-2-oxa-1,3-diazole (IANBD) and 6
      acryloyl-2-(dimethylamino)-naphthalene (acrylodan). This combined genetic and
      chemical modification places the fluorophores close to the maltose binding site
      such that when the ligand is added the fluorescence intensity of the labels
      increases by 60-180% over that of the ligand-free form. This change is consistent
      with the fluorophores being buried when the conformation of the protein changes
      with maltose binding. Titration of the labeled mutant proteins yields
      dissociation constants for maltose of 62 +/- 0.2 and 0.8 +/- 0.01 microM
      respectively for the IANBD and acrylodan modifications. The application of this
      strategy of combined genetic and chemical modification to the development of
      reagentless fluorescence sensing is discussed.

PMID- 7802266
TI  - Maximum blood savings by acute normovolemic hemodilution.
AB  - Acute normovolemic hemodilution (ANH) entails collecting blood from a patient
      immediately prior to surgery with concurrent fluid infusion to maintain
      intravascular volume constant. Blood collected during ANH is later reinfused to
      replace the red cell losses that occur during surgery. This technique is
      advocated as a means to reduce or eliminate homologous blood transfusion during
      surgery. Published guidelines for performing ANH vary, and the literature does
      not describe how to perform ANH to achieve the maximum benefit for a given
      patient. To evaluate how to save red blood cells as much as possible via ANH, and
      to determine the maximum benefit that can be expected, we developed a mathematic
      model of the process. Using the model, the net red cell mass savings possible
      when using ANH can be calculated given the patient's weight, initial hematocrit
      and minimum safe hematocrit. Results are reported to demonstrate the impact of
      the initial hematocrit and minimum safe hematocrit on the red cell savings
      possible with ANH. The data indicate that ANH does indeed save red blood cells
      that would otherwise be lost during surgery. However, the red cell savings
      possible when using ANH are not as much as typically published and, a degree of
      hemodilution more than that which is typically recommended is necessary to
      achieve even modest red cell savings.

PMID- 7802265
TI  - An innovative cold tail-flick test: the cold ethanol tail-flick test.
AB  - An innovative antinociceptive test, the cold ethanol tail-flick test (CET), was
      developed for evaluating the actions of opioid analgesics. To select an optimal
      operation temperature range for the CET, temperatures from -5 degrees C to -30
      degrees C were screened. After screening, temperatures ranging between -20
      degrees C and -30 degrees C were both strong and effective enough to act as a
      noxious cold stimulus. In the following study, -20 degrees C was selected as the
      cold stimulus for the CET. The sensitivity and specificity of this test were
      challenged by opioid analgesics: an agonist (morphine) and two agonist
      antagonists (buprenorphine and nalbuphine), two tranquilizers (droperidol and
      diazepam), and four nonopioid analgesics (acetaminophen, aspirin, indomethacin,
      and ketoprofen). The sensitivity of the CET was also compared with the assays
      using heat (radiant heat and hot water). The AD50 values determined by the CET
      for morphine, buprenorphine, and nalbuphine were 0.16 mg/kg, 0.22 micrograms/kg,
      and 0.19 mg/kg, respectively. Naloxone, an opioid antagonist, blocked the
      antinociceptive effects of these opioids which were determined by the CET.
      Furthermore, the tranquilizers and nonopioid analgesics did not show any activity
      in the CET. Our results show that not only can the CET assess the antinociceptive
      activity of both opioid agonist and mixed agonist-antagonist, it also possess the
      characteristics of sensitivity, specificity, simplicity, and reproducibility.

PMID- 7802267
TI  - Dexmedetomidine partially attenuates the sympathetically mediated systemic and
      coronary hemodynamic effects of cocaine.
AB  - The hemodynamic effects of cocaine may be modulated by drugs which interact with
      central and peripheral adrenoceptors. This investigation examined the systemic
      and coronary hemodynamic effects of cocaine in conscious dogs with and without
      premedication with dexmedetomidine (DM). Three groups consisting of 24
      experiments were performed using eight dogs chronically instrumented for
      measurement of aortic and left ventricular pressure, left ventricular dP/dtmax,
      diastolic coronary blood flow velocity, cardiac output, and subendocardial
      segment length. On separate experiment days, systemic and coronary hemodynamics
      were recorded after cocaine (0.5 mg/kg intravenously [I.V.]) with or without DM
      pretreatment (2 or 4 micrograms/kg I.V.). Cocaine caused increases in heart rate,
      mean arterial pressure, left ventricular systolic and end-diastolic pressures,
      dP/dtmax, cardiac output, systemic vascular resistance, and pressure-work index
      in conscious dogs. Pretreatment with DM attenuated increases in heart rate,
      dP/dtmax, cardiac output, and pressure-work index produced by cocaine. Systemic
      vascular resistance increased after the administration of cocaine with and
      without DM pretreatment; however, systemic vascular resistance remained higher
      after cocaine in DM-pretreated dogs compared to untreated dogs. Increases in
      diastolic coronary vascular resistance, but no change in coronary flow velocity,
      were observed with cocaine alone. In contrast, cocaine increased diastolic
      coronary blood flow velocity without change in diastolic coronary vascular
      resistance when administered after DM. The results indicate that increases in
      heart rate, myocardial contractility, and myocardial oxygen consumption caused by
      cocaine were attenuated by DM pretreatment. However, cocaine-induced increases in
      systemic vascular resistance were augmented by DM, suggesting an additive effect
      at peripheral vascular alpha adrenoceptors.

PMID- 7802268
TI  - Effectiveness of the self-inflating bulb for verification of proper placement of
      the Esophageal Tracheal Combitube.
AB  - The esophageal tracheal Combitube (ETC; Sheridan Catheter Corporation, Argyle,
      NY) is a twin-lumen tube used to establish emergency ventilation. After blind
      placement, ventilation is performed via the proximal lumen if it is in the
      esophagus or via the distal lumen if it is in the trachea. This investigation was
      designed to test the reliability of the self-inflating bulb (SIB) in identifying
      the location of the ETC and facilitating its proper positioning in anesthetized
      patients. In Group 1 (n = 26), the ETC was introduced blindly. In Group 2 (n =
      20), the tube was placed in the trachea (eight patients) or once in the trachea
      and once in the esophagus, randomly (12 patients) under direct vision rigid
      laryngoscopy by the anesthesiologist performing the intubation. In both groups,
      the efficacy of the SIB in identifying the location of the ETC was tested by a
      second blinded anesthesiologist. In Group 1, blind insertion of the ETC resulted
      in esophageal placement in all patients, and in each case was correctly
      identified. The second anesthesiologist reported no reinflation when the
      compressed SIB was connected to the distal lumen. When the compressed SIB was
      connected to the proximal lumen, instantaneous reinflation was observed in 23
      patients, delayed reinflation (2-4 s) in two and no reinflation (> 4 s) in one
      patient. Instantaneous reinflation occurred in these three patients after
      repositioning of the ETC. In Group 2, the second anesthesiologist correctly
      identified the location of the ETC in all cases. The results confirm previous
      findings that blind introduction of the ETC leads to esophageal placement and
      yields adequate ventilation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7802269
TI  - Direct comparative effects of isoflurane and desflurane on sympathetic ganglionic
      transmission.
AB  - Although the sympathetic ganglion is an important site of peripheral regulation,
      few studies have examined the effect of anesthetics on synaptic transmission. In
      the present study we compared the actions of desflurane with those of isoflurane
      on synaptic transmission and neurotransmitter release in the stellate ganglion.
      In the electrophysiologic group, 14 stellate ganglia were isolated from adult
      mongrel dogs after halothane anesthesia, desheathed, and superfused with Krebs'
      solution. Compound action potentials (CAP) were induced by supramaximal
      stimulation of the preganglionic T3-ramus at a low frequency of 0.4 Hz and were
      recorded from the postganglionic ventral ansa subclaviae. Each ganglion was
      exposed to two levels of anesthetics (equivalent to 1 and 2 minimum alveolar
      anesthetic concentration [MAC]), followed by an anesthetic-free washout period.
      While equianesthetic concentrations of isoflurane and desflurane caused
      essentially equipotent suppression of ganglionic transmission, desflurane was
      more efficacious than isoflurane, both with respect to the onset of and recovery
      from the inhibition of synaptic activity. In the electrochemical group, 25
      ganglia were exposed to both anesthetics at a high concentration (equivalent to
      between 1.82 and 1.95 MAC) during maximal and submaximal current stimulations,
      and the release of actylcholine (ACh) in the superfusate was measured with liquid
      chromatography. Although desflurane and isoflurane caused a significant
      depression of CAP, neither anesthetic inhibited the release of ACh in the
      superfusate at either maximal or submaximal current stimulations. These results
      indicate that the suppression of ganglionic activity is equipotent for both
      anesthetics based on equivalent MAC values, but that desflurane is more
      efficacious than isoflurane with respect to onset and recovery at the higher
      concentrations of anesthetics.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7802270
TI  - Splanchnic and renal sympathetic activity in relation to hemodynamics during
      isoflurane administration in pigs.
AB  - The aim of the present study was to investigate the impact of isoflurane on
      regional neurogenic mechanisms in the control of vascular tone. Therefore,
      regional determinations of sympathetic activity and hemodynamics were made in
      chloralose-anesthetized swine before and during administration of 1.4%
      isoflurane. Sympathetic activity was examined from spillover of norepinephrine
      (NE) into the circulation using an isotope dilution technique. Administration of
      isoflurane caused a marked decrease in mesenteric (65 +/- 9 pmol.min-1.100 g-1; P
      < 0.05) NE spillover. Renal NE spillover was moderately decreased (25 +/- 6
      pmol.min-1.100 g-1; P < 0.05), whereas liver NE spillover did not change
      significantly during isoflurane administration, suggesting that liver sympathetic
      activity is maintained at this level of isoflurane anesthesia. Total body NE
      spillover decreased (13 +/- 2 pmol.min-1.100 g-1, P < 0.05). Thus, isoflurane
      affected sympathetic outflow in a regionally differentiated pattern. Significant
      correlations were found between total body, mesenteric, and renal NE spillovers
      and vascular resistances, supporting the concept that the observed reductions in
      vascular resistances in these circulations during isoflurane administration were
      in part a consequence of reduced sympathetic outflow. In the liver circulation,
      no correlation was found between NE spillover and liver portal or liver arterial
      vascular resistances. Liver arterial resistance was significantly reduced during
      isoflurane administration while liver portal resistance was unchanged.
      Administration of isoflurane caused reductions in cardiac output, renal, portal,
      hepatic arterial, and total hepatic blood flows, whereas mesenteric blood flow
      was unchanged. To summarize, isoflurane decreased mesenteric and renal NE
      spillover with concomitant reductions in vascular resistances.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7802271
TI  - Oxygen saturation in children in the postoperative period.
AB  - Some adult patients have periods of significant oxygen desaturation after surgery
      but, other than for immediately after surgery in the recovery room, few data are
      available in children. We monitored overnight paired preoperative and
      postoperative oxygen saturations in 19 children, and overnight postoperative
      saturations in 50 additional children to determine whether children have periods
      of desaturation in the postoperative period. The children underwent surgery
      usually associated with moderate to severe postoperative pain, and were treated
      with epidural, intravenous, or intramuscular opioids. In the group of 19 children
      mean (SD) preoperative oxygen saturation was 96.6% +/- 1.3%, and the mean
      postoperative saturation was 95.7% +/- 1.2%. The average change was 0.88% +/-
      1.52%. The 95% confidence interval of the paired difference was 0.13% to 1.6%.
      There was no significant difference in the percent of monitored time that the
      patients spent with an oxygen saturation less than 95%, 90%, 85%, or 80%. In the
      50 children monitored only in the postoperative period, mean (SD) saturation was
      97.8% +/- 1.9%. The data show that, in contrast to some reports in adults, this
      group of children did not have multiple episodes of clinically significant oxygen
      desaturation in the postoperative period.

PMID- 7802272
TI  - Aging increases pharmacodynamic sensitivity to the hypnotic effects of midazolam.
AB  - The effect of aging on the pharmacodynamics of midazolam was investigated in a
      double-blinded study involving 39 consenting patients ranging in age from 39 to
      77 yr. Midazolam was infused intravenously (i.v.) using a pharmacokinetic model
      driven drug infusion device to achieve a plasma midazolam concentration that was
      held constant for the 10-min duration of the study. Blood samples were obtained
      from the radial artery at 5 and 10 min for subsequent measurement of the plasma
      midazolam concentrations. With the 10-min sample, the patients were also assessed
      for the presence or absence of responsiveness to verbal command. To ensure that
      the pharmacodynamic end-point was assessed under the condition of a relative
      steady-state effect-site midazolam concentration, only those patients (n = 33) in
      whom the plasma midazolam concentration at 10 min was within 30% of the measured
      concentration at 5 min were included in the subsequent data analyses. Logistic
      regression was used to fit the verbal command response/no response data to a
      mathematical model that included patient age and the plasma midazolam
      concentration measured at 10 min. Cp50, the steady-state plasma midazolam
      concentration at which 50% of patients would be expected not to respond to a
      specific stimulus (e.g., verbal command), was calculated as a function of age
      from the parameterized logistic model. The midazolam Cp50 for response to verbal
      command decreased significantly (P = 0.034) with increasing patient age,
      demonstrating that aging increases pharmacodynamic sensitivity to the hypnotic
      effects of midazolam independent of pharmacokinetic factors.

PMID- 7802273
TI  - Postoperative tracheal extubation.

PMID- 7802274
TI  - Spinal cord synaptic plasticity and chronic pain.

PMID- 7802275
TI  - The intraoperative diagnosis of atrial myxoma by transesophageal echocardiogram.

PMID- 7802277
TI  - Pulmonary artery obstruction by aortic aneurysm mimicking pulmonary embolism.

PMID- 7802276
TI  - Intraoperative diagnosis of left atrial myxoma.

PMID- 7802278
TI  - Atypical facial "neuralgia".

PMID- 7802279
TI  - Patient-administered alfentanil for wound dressing changes in a non-intensive
      care unit setting.

PMID- 7802280
TI  - Noninvasive monitoring of cerebral perfusion by transcranial Doppler during
      fulminant hepatic failure and liver transplantation.

PMID- 7802281
TI  - Infants tolerate spinal anesthesia with minimal overall autonomic changes:
      analysis of heart rate variability in former premature infants undergoing hernia
      repair.
AB  - Unlike adults, neonates tolerate high thoracic spinal anesthesia with minimal
      changes in heart rate (HR) and arterial blood pressure. To examine the potential
      autonomic regulatory mechanisms which may account for these findings, the
      relation between short-term heart rate variability (HRV) and respiratory activity
      was analyzed in a group of eight ASA grade II former premature infants undergoing
      high thoracic spinal anesthesia for inguinal hernia repairs. Quantitative
      measures of sympathetic (As) and parasympathetic (Ap) modulation of HR were
      derived. HR, arterial blood pressure, and a calibrated respiratory signal were
      recorded during 4.4-min stable epochs in eight subjects 1) preoperatively, 2)
      postincision after high thoracic spinal anesthesia, and 3) during an active sleep
      state in the postoperative period. Power spectral analysis of HRV and respiratory
      power yielded measures of low-frequency power (LFP: 0.02-0.15 Hz) and high
      frequency power (HFP: 0.15-0.8 Hz). Transfer function analysis between
      respiratory activity and HR were used to quantify As and Ap. All subjects had
      successful high thoracic spinal anesthesia with highest levels ranging from C7
      T4. Mean HR, blood pressure, and respiratory power did not change significantly
      with high thoracic spinal anesthesia. LFP and HFP both decreased significantly,
      whereas the LFP/HFP ratio remained stable. Group mean As and Ap both decreased,
      but the changes were not significant. Despite overall cardiovascular stability,
      HRV decreased with high thoracic spinal anesthesia, but the balance between LFP
      and HFP remained stable, suggesting that the reflex response to high thoracic
      spinal anesthesia was predominantly diminished parasympathetic modulation of
      cardiac function. The expected decrease in HR and blood pressure from the
      sympatholysis which results from high thoracic spinal anesthesia were apparently
      offset by withdrawal of cardiac vagal activity.

PMID- 7802282
TI  - Pharyngeal emphysema with airway obstruction as a consequence of laparoscopic
      inguinal herniorrhaphy.

PMID- 7802283
TI  - A device for measuring the degree of lateral pelvic tilt during supine
      recumbency.

PMID- 7802284
TI  - Aortic clamp hypertension is avoidable.

PMID- 7802285
TI  - Another hazardous gas supply misconnection.

PMID- 7802286
TI  - Infant hyperkalemic arrest after succinylcholine.

PMID- 7802287
TI  - Recent changes in the package insert for succinylcholine chloride: should this
      drug be contraindicated for routine use in children and adolescents? (Summary of
      the discussions of the anesthetic and life support drug advisory meeting of the
      Food and Drug Administration, FDA building, Rockville, MD, June 9, 1994)

PMID- 7802288
TI  - Does end-tidal PCO2 predict the temperature-uncorrected or corrected PaCO2 during
      hypothermia?

PMID- 7802289
TI  - A method for preventing throat pack retention.

PMID- 7802290
TI  - The accuracy of the 5%-25% (T1-T3) twitch recovery interval in predicting the
      speed of spontaneous recovery from mivacurium-induced neuromuscular blockade.

PMID- 7802292
TI  - Antecubital central venous catheters revisited.

PMID- 7802291
TI  - Nonvasodilating vasodilating anesthetics?

PMID- 7802293
TI  - The laryngeal mask airway and laryngeal polyposis.

PMID- 7802294
TI  - A case of hyponatremia while using ethanol labeling for endometrial resection.

PMID- 7802295
TI  - Another explanation for reduced meperidine consumption in the immediate
      postoperative period.

PMID- 7802296
TI  - The effect of esmolol given during cardiopulmonary bypass.
AB  - beta-Adrenergic antagonism decreases the size of myocardial infarction and
      provides myocardial protection during hypothermic arrest for cardiac surgery.
      However, concern regarding the negative inotropic and chronotropic effects of
      beta-adrenergic antagonism persisting after cardiopulmonary bypass (CPB) has
      impeded the use of esmolol for this purpose during cardiac surgery. This is a
      randomized, double-blind prospective study of the effects of esmolol infused
      during CPB and the effects of hypothermic CPB on esmolol. Patients scheduled for
      CPB were randomized to receive intravenous esmolol (300.micrograms.kg-1.min-1
      during CPB after a bolus of 2 mg/kg prior to CPB) or placebo. Infusion was
      stopped at 10 min after release of aortic cross-clamp. Hemodynamics were
      measured, as well as serum esmolol, catecholamines, lactate, and potassium.
      Postoperative variables measured included electrocardiographic changes, creatine
      kinase (CK)-MB fractions, post-CPB dysrhythmias and drugs, hospitalization time
      and cost, and mortality. Esmolol was administered to 16 patients and placebo to
      14. Esmolol levels reached a high of 10.5 +/- 0.9 micrograms/mL during CPB, but
      decreased to 0.1 +/- 0.02 microgram/mL within 30 min after stopping infusion.
      Cardiac indices (cardiac index, stroke volume index, left cardiac work index,
      left ventricular stroke work index, right cardiac work index, and right
      ventricular stroke work index) were higher in the esmolol group for the first
      hour post-CPB (P < 0.05). Systemic arterial lactate and coronary sinus lactate
      were lower in the esmolol group after CPB (P < 0.05), but myocardial lactate
      extraction was not significantly different between groups. After CPB, hemoglobin
      was lower in the esmolol group (P < 0.05) due to longer CPB and aortic cross
      clamp time (P < 0.05), but oxygen consumption was less than in the control group
      (P < 0.05). Post-CPB serum potassium was higher in the esmolol group (P < 0.05).
      Results are confounded by more chronically beta-adrenergically blocked patients
      randomized to the esmolol group (P < 0.05). Esmolol infused during CPB in this
      series of patients was associated with high concentrations during CPB but did not
      result in any adverse clinical effects after CPB.

PMID- 7802297
TI  - Perioperative transesophageal echocardiography: the anesthesiologist as cardiac
      diagnostician.

PMID- 7802298
TI  - Comparison between transesophageal Doppler echocardiography and nuclear
      cardioangiography for the evaluation of left ventricular filling during coronary
      artery bypass grafting.
AB  - This study examines the relative contribution of early (E) and atrial (A) filling
      of the left ventricle. Ten patients were studied under anesthesia before and
      after coronary artery bypass grafting (CABG) using measurements of the mitral
      velocity-time integral (VTI) with transesophageal pulsed Doppler echocardiography
      and nuclear angiocardiography simultaneously. Thermodilution cardiac output
      measurements were made simultaneously in order to express the E and A filling in
      quantitative terms. The mean difference between methods in estimating E filling
      was -1.0 mL and the figures for the mean +/- 2 SD were 5.7 and -7.8 mL, r = 0.98
      using regression analysis. The mean difference during A filling was 0.9 mL and
      the corresponding figures for the mean +/- 2 SD were 7.9 and -6.1 mL, r = 0.88.
      There was a reduction in the volume entering the left ventricle during the E
      filling (42-26 mL) and in the A phase (27-22 mL) from before surgery in
      comparison to after CABG. There was good agreement between transesophageal
      Doppler echocardiographic and nuclear angiocardiographic methods concerning the
      volume contribution during E and A phases of left ventricular filling.

PMID- 7802299
TI  - Effects of adenosine infusion on systolic and diastolic left ventricular function
      after coronary artery bypass surgery: evaluation by computer-assisted
      quantitative 2-D and Doppler echocardiography.
AB  - The effects of adenosine on central hemodynamics, ST-segment changes, and left
      ventricular (LV) systolic and diastolic function, determined by transesophageal 2
      D and Doppler echocardiography, were investigated in 20 patients shortly after
      coronary surgery. After control measurements, adenosine was infused at
      incremental infusion rates (30, 60, and 120 micrograms.kg-1.min-1). Adenosine
      caused dose-dependent increases in heart rate (68.0 +/- 11.2-74.0 +/- 15.7 bpm),
      cardiac output (3.23 +/- 0.76-4.17 +/- 0.67 L/min), and stroke volume (48.8 +/-
      12.5-56.7 L/min), and stroke volume (48.8 +/- 12.5-56.7 mL), decreases in
      arterial pressure (84.8 +/- 16.6-63.3 +/- 15.2 mm Hg), and systemic and pulmonary
      vascular resistances (1994 +/- 510-1106 +/- 309 and 209 +/- 54-116 +/- 58
      dyne.s.cm-5, respectively), but no changes in cardiac filling pressures. The mean
      ST segment was slightly but significantly depressed by adenosine (from 0.003 to
      0.019 mV). Analysis of LV wall motion showed that adenosine caused no changes in
      the global area ejection fraction (GAEF), the segmental area ejection fraction
      (SAEF), or in the SAEF/GAEF ratio, indicating that no regional wall motion
      abnormalities appeared. Maximum early and late diastolic flow rates (Emax, Amax),
      determined by mitral Doppler analysis, increased (from 30.1 +/- 14.8 to 40.1 +/-
      24.1 and from 37.8 +/- 15.7 to 46.4 +/- 31.3 cm/s, respectively), as did the
      deceleration slope of the early diastolic filling (from -151 +/- 67 to -210 +/-
      107 cm/s-2), whereas no changes were found in the ratio between Emax and Amax,
      the deceleration time of early diastolic filling, or the velocity time integrals
      of early or late diastolic filling.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7802301
TI  - Intravenous midazolam suppresses noxiously evoked activity of spinal wide dynamic
      range neurons in cats.
AB  - The effects of intravenously (i.v.) administered midazolam on noxiously evoked
      activity of spinal wide dynamic range (WDR) neurons were investigated in
      decerebrate, spinal-cord-transected cats. Extracellular, single-unit recordings
      were measured during stimulation by pinching the receptive field on the hind paw
      and the effect of midazolam at doses of 0.25, 0.5, 1, 2, and 4 mg/kg were
      measured. Two series of experiments were performed to characterize the analgesic
      effects of midazolam. In the first, dose-response experiments (n = 59)
      demonstrated a dose-dependent suppression of the noxiously evoked activity of
      spinal WDR neurons after midazolam administration. This effect of midazolam was
      maximal at a dose of 1 mg/kg i.v.. The second series of experiments (n = 14)
      demonstrated that a benzodiazepine antagonist, flumazenil (n = 8), promptly
      reversed the effect of midazolam, while an opioid antagonist, naloxone (n = 6),
      had no effect on the effect of midazolam. The present study demonstrates that
      i.v. administered midazolam suppresses noxiously evoked activity of spinal WDR
      neurons that is reversible by a benzodiazepine antagonist. This is consistent
      with an analgesic action of midazolam.

PMID- 7802300
TI  - Transient atrioventricular block after release of aortic cross-clamp.
AB  - To determine the incidence of atrioventricular (A-V) block, 86 patients, aged
      58.9 +/- 10.4 yr, undergoing elective coronary artery bypass grafting (CABG)
      during aortic cross-clamping (ACC) and cold potassium cardioplegia were
      investigated. The incidence and duration of complete A-V block after release of
      the aortic cross-clamp was monitored. Twenty-four percent of the patients
      developed complete A-V block that required temporary pacing for a mean time of 66
      +/- 39 min. The volume of cardioplegia used was not significantly different
      between the patients who developed A-V block and the patients who had no block.
      The serum potassium level at the time of release of the aortic cross-clamp was
      within the normal range in both groups. Six factors were correlated with the
      development of A-V block: old age, preparation by a combination of beta
      adrenergic blockers and calcium channel blockers, preoperative bradycardia, the
      number of vessels grafted, as well as the duration of ACC. Also, the serum
      potassium level at the time of release of the aortic cross-clamp was
      significantly higher in the patients who developed A-V block. The high incidence
      of A-V block in elderly patients undergoing multiple coronary vessel grafting
      during a prolonged ACC time suggests that suboptimal myocardial preservation may
      be the main predisposing factor.

PMID- 7802302
TI  - Effect of ketanserin on global cerebral blood flow and middle cerebral artery
      flow velocity.
AB  - The aim of this study was to examine the influence of ketanserin, a 5
      hydroxytryptamine antagonist antihypertensive agent, on the relationship between
      cerebral blood flow (CBF) and middle cerebral artery flow velocity (Vmean MCA)
      and to compare Doppler-sonographic indices of downstream resistance (pulsatility
      index, PI; resistance index, RI) with calculations of cerebrovascular resistance
      (CVR) in 17 male patients under fentanyl/midazolam anesthesia. CBF was measured
      with the Kety-Schmidt technique using argon as a tracer. Cerebral perfusion
      pressure (CPP) was calculated as the difference between mean arterial pressure
      (MAP) and jugular bulb pressure. Measurements of Vmean MCA and determinations of
      PI and RI were performed by use of a 2-MHz transcranial Doppler ultrasound
      device. All variables were measured at normo- and moderate hypocapnia before and
      after intravenous (i.v.) bolus administration of 0.3 mg/kg ketanserin followed by
      an infusion of 0.06 mg.kg-1.h-1. Ketanserin changed neither average CBF nor Vmean
      MCA. The CO2 reactivity of Vmean MCA was significantly lower than the CO2
      reactivity of CBF (P < 0.01); however, ketanserin did not change the relationship
      between CBF and Vmean MCA. During hypocapnia, CVR as well as PI and RI
      significantly increased (P < or = 0.01), indicating consistent directional
      changes in arteriolar resistance and flow velocity pulsatility. In contrast,
      after i.v. administration of ketanserin, CVR decreased (P < 0.05), whereas both
      Doppler-derived indices increased (P < 0.01). These results suggest that
      ketanserin in a clinically relevant dose does not alter the validity of serial
      Vmean MCA measurements as an index of global CBF and that ketanserin does not
      change the diameter of middle cerebral arteries (MCAs). Doppler-derived indices
      of pulsatility and resistance, which are supposed to estimate changes in
      downstream resistance, reflect changes, after administration of ketanserin, in
      systemic hemodynamics rather than changes in CVR.

PMID- 7802303
TI  - Postoperative apnea, bradycardia, and oxygen desaturation in formerly premature
      infants: prospective comparison of spinal and general anesthesia.
AB  - Eighteen formerly premature infants scheduled for inguinal herniorrhaphy and who
      were less than 51 wk postconceptional age were assigned to either the general
      anesthesia group (GA: atropine, halothane, and nitrous oxide) or the spinal
      anesthesia group (SA: hyperbaric tetracaine). Twelve-hour, three-channel
      continuous recordings of respiratory rate (chest wall impedance),
      electrocardiogram (ECG), and hemoglobin O2 saturation (SpO2) were obtained
      preoperatively and after surgery. These were analyzed for short (11-15s) and long
      (> 15 s) apnea spells, periodic breathing, and episodes of hemoglobin oxygen
      desaturation and bradycardia. Infants in the GA group had lower postoperative
      minimum SpO2 (68.7% +/- 11.4%) and minimum heart rate (79 bpm +/- 19) than
      infants in the SA group (80.7% +/- 9.2%, and 109 bpm +/- 30, respectively; P <
      0.05) and had lower postoperative minimum SpO2 and minimum heart rate than they
      had preoperatively (79.0% +/- 13.7%, and 93 bpm +/- 31, respectively; P < 0.05);
      pre- and postoperative studies in the SA group did not differ. There were no
      differences in the incidence of postoperative central apnea. We conclude that
      spinal anesthesia reduces postoperative hemoglobin oxygen desaturation and
      bradycardia in formerly premature infants undergoing inguinal herniorrhaphy.

PMID- 7802304
TI  - The effects of intravenous and epidural sufentanil in the chronic maternal-fetal
      sheep preparation.
AB  - This study examines the placental transfer and hemodynamic and acid-base changes
      after intravenous (i.v.) and epidural administration of sufentanil in the
      chronically instrumented maternal-fetal sheep preparation. A dose of 50
      micrograms sufentanil was injected either i.v. or epidurally into seven ewes.
      Neither i.v. nor epidural injection of sufentanil affected maternal mean arterial
      pressure (MMAP), uterine blood flow (UBF), maternal heart rate (MHR), fetal mean
      arterial pressure (FMAP), fetal heart rate (FHR), or blood gases and acid-base
      status in mother and fetus, After i.v. administration, a peak sufentanil level of
      1.28 ng/mL +/- 0.285 (SD) was detected in maternal plasma. A peak plasma level of
      0.037 ng/mL +/- 0.041 (SD) was attained in the fetus. A constant maternal-fetal
      concentration ratio of 5.5 from 15-60 min after the i.v. injection was found.
      After epidural injection a mean peak plasma level of 0.059 ng/mL +/- 0.042 (SD)
      was reached in the mother 25 min after injection. Sufentanil levels were
      undetectable in fetal plasma after epidural injection into the mother. Because
      placental transfer of sufentanil is small, the maternal and fetal cardiovascular
      and acid-base effects are minimal in the pregnant ewe.

PMID- 7802305
TI  - Epidural sufentanil for postoperative patient-controlled analgesia (PCA) with or
      without background infusion: a double-blind comparison.
AB  - To evaluate the usefulness of a concurrent infusion in patient-controlled
      epidural analgesia (PCEA), 40 patients scheduled for elective cesarean section
      under a combined spinal-epidural technique were assigned randomly in a double
      blind fashion to receive sufentanil by PCEA with a concomitant infusion of either
      sufentanil or saline. The sufentanil 24-h consumption was significantly (P <
      0.001) higher in those patients receiving the opioid-containing infusion (212.7
      +/- 9.5 vs 128.4 +/- 10.8 micrograms, SEM). The number of additional demands and
      the quality of sleep did not differ between the two groups. The degree of
      sedation was significantly less pronounced in patients treated with incremental
      sufentanil doses only. The visual analog scale (VAS) pain scores at rest were
      identical in both groups except at 6 h (2.5 +/- 0.4 vs 3.7 +/- 0.3, in favor of
      the patients treated with the sufentanil background infusion). We conclude that,
      except for a lower pain score during the initial hours, a background infusion in
      PCEA with sufentanil does not offer major advantages in terms of sleep quality or
      sufentanil consumption. Side effects may be more pronounced owing to increased
      drug administration.

PMID- 7802306
TI  - Comparison of different methods of administering droperidol in patient-controlled
      analgesia in the prevention of postoperative nausea and vomiting.
AB  - We performed a double-blind, placebo-controlled study to evaluate the different
      methods of administering droperidol in patients using patient-controlled
      analgesia (PCA) with morphine. Eighty patients undergoing major orthopedic
      procedures received temazepam 0.2 mg/kg orally followed by induction of general
      anesthesia with propofol 2.5 mg/kg, fentanyl 2 micrograms/kg, and vecuronium 0.1
      mg/kg. Anesthesia was maintained with nitrous oxide, oxygen, and enflurane. At
      the end of surgery, all patients received PCA with morphine (0.5 mg/mL, bolus
      dose 1 mg, and lockout interval 5 min. Before commencement of PCA, patients were
      randomized to receive droperidol 1.25 mg immediately and, in addition, droperidol
      0.16 mg with each PCA dose (Group 1), droperidol 1.25 mg immediately (Group 2),
      droperidol 0.16 mg with each PCA dose (Group 3), and no droperidol (Group 4).
      Incidence of nausea and vomiting, request for rescue antiemetics, sedation score,
      and side effects were recorded every 4 h. Droperidol significantly reduced the
      incidence of postoperative nausea and vomiting (PONV) (P < 0.01) and request for
      rescue antiemetic (P < 0.01) compared to placebo. However, there was no
      difference in the incidence of PONV between droperidol given either as a single
      dose at the end of surgery (Group 2) or mixed in morphine PCA (Group 3). The
      addition of droperidol in PCA after an initial dose (Group 1) should be avoided,
      as it resulted in more sedation and no further reduction in the incidence of PONV
      compared to Groups 2 and 3.

PMID- 7802307
TI  - Postoperative analgesia after co-administration of clonidine and morphine by the
      intrathecal route in patients undergoing hip replacement.
AB  - Postoperative analgesia after intrathecal co-administration of clonidine
      hydrochloride (75 micrograms) and morphine sulfate (0.5 mg) was compared with
      analgesia produced after either intrathecal morphine (0.5 mg) or 0.9% sodium
      chloride in 90 patients undergoing total hip replacement under bupivacaine spinal
      anesthesia. Patient-controlled morphine requirements were significantly reduced
      (P < 0.001) postoperation by both clonidine/morphine (median 5 mg/24 h) and
      morphine (median 7 mg/24 h) compared with control (saline) (median 28 mg/24 h).
      However, no significant additional reduction in postoperative analgesic
      requirements was shown with the clonidine/morphine combination compared with
      morphine alone. Visual analog pain scores, although good in all groups at all
      times, were significantly poorer in the control group at 2 h (P < 0.04) and 4 h
      (P < 0.001) after operation compared with both treatment groups, and
      significantly poorer than the clonidine/morphine group at 6 h (P < 0.002) and 24
      h (P < 0.009) postoperation. Mean arterial blood pressure was significantly lower
      in the clonidine/morphine group than in the two other groups (P < 0.001) between
      2 and 5 h after operation. The incidence of emesis was similar in the
      clonidine/morphine and morphine groups and was significantly more than in the
      control group.

PMID- 7802308
TI  - The antinociceptive effect of S-(+)-ibuprofen in rabbits: epidural versus
      intravenous administration.
AB  - This study was designed to determine whether systemic absorption plays any role
      in the antinociceptive effect of epidural (EP) sodium S(+)-ibuprofen (IB). One
      week after surgical implantation of EP catheters, six rabbits were given EP
      injections with either normal saline (NS) 0.4 mL or IB 10 mg in 0.4 mL NS (Group
      1) on separate days. Each animal was injected with IB 10 mg intravenously (i.v.)
      on another day. Six control rabbits (Group 2) had neither surgery nor any
      injection. Analgesic testing was performed using electric stimulation through two
      electrocardiogram (ECG) skin electrodes with built-in adhesive, attached to
      shaved hip areas using 50 V, 1 Hz, 3 ms, before and 0.5,1,2 and 3 h after
      injection in Group 1, and in similar times in controls. The 95% confidence
      intervals (CI) of the mean difference between baseline and maximal nociceptive
      response latency of all groups were compared using analysis of covariance
      (ANCOVA) adjusted for baseline measurements. This comparison covered all possible
      pairs among all groups. Significant antinociceptive effects were seen after EP IB
      but not after control or i.v. IB. Neither motor dysfunction nor evidence of
      systemic toxicity or neurotoxicity was observed in any animal.

PMID- 7802309
TI  - Prolongation of epidural anesthesia in the rabbit with the use of a biodegradable
      copolymer paste containing lidocaine.
AB  - Prolongation of the drug effect using a drug-delivery system has recently been
      introduced in local anesthesia. In this study, we investigated the prolonging
      effect of an epidurally injected biodegradable copolymer paste containing 10%
      lidocaine (Lid-CoPol). Twenty-nine rabbits were studied. A catheter was placed in
      the epidural space at the level of L6-7 in each animal. A solution of 10%
      lidocaine (Group I, n = 12), or a copolymer containing 10% lidocaine (Lid-CoPol),
      (Group II, n = 12) or copolymer paste only (Group III, n = 5) was injected
      epidurally at a dose of 0.15 mL/kg. The effect of each drug was assessed by
      evaluation of response to pain stimulation and of the degree of motor block
      produced. The plasma lidocaine concentration was also measured consecutively in
      five animals of both Groups I and II. The duration of sensory and motor block of
      Lid-CoPol was 800% and 975% longer, respectively, than that of plain lidocaine
      solution. Plasma lidocaine concentration reached a maximum 5 min after injection
      (5.5 +/- 0.5 micrograms/mL) in Group I. In Group II, the level reached a maximum
      30 min after injection (3.7 +/- 1.5 micrograms/mL). The findings are attributed
      in part to the slow release of lidocaine from the biodegradable copolymer paste,
      which is suggested as a new drug-delivery system for local anesthetics.

PMID- 7802310
TI  - [A clinical-experimental study of narcotic properties of opiate receptor agonists
      antagonists and experience in their use in drug addiction practice].
AB  - Narcogenic characteristics of opiate agonists-antagonists were studied in drug
      abusers. It is shown that buprenorphine, butorphanol, nalbuphine hydrochloride,
      but not tramadol, have high narcogenic potential. Opportunities for these drugs
      in narcological practice are outlined.

PMID- 7802311
TI  - [Use of tramal in the treatment and prevention of pain syndrome in children].
AB  - The authors analyze the results of tramal use for prevention and treatment of the
      painful syndrome caused by surgical interventions in more than 200 children of
      various age groups. The most promising domains of the drug use are shown,
      particularly in infants and babies. Indications for the drug use, its doses, as
      well as advantages are enumerated. Methods for objective and subjective
      evaluation of pain used in pediatric surgery are presented.

PMID- 7802312
TI  - [Multicomponent general anesthesia using analgesic butorphanol tartrate (beforal)
      in thoracic surgery].
AB  - Two schemes of anesthesia were used in 34 patients, making use of beforal, an
      agonist-antagonist of opioid receptors, as an analgesic component of total
      anesthesia during operations on the lungs. To improve neurovegetative protection,
      adrenomimetic clofelin was added to the Ist scheme and neuroleptic droperidol to
      the IInd. Use of beforal as an analgesic component of balanced total anesthesia
      in thoracal surgery in combination with both clofelin and droperidol ensured a
      sufficient level of anesthesiologic protection. Combination of beforal with
      clofelin, however, prevented hyperdynamic circulatory reactions at traumatic
      stages of the operation and intubation of the trachea and stabilized thermal
      homeostasis parameters, this indicating a more potent neurovegetative protection
      in this scheme of anesthesia.

PMID- 7802313
TI  - [Effects of opioid analgesics on pulmonary ventilation and metabolism in patients
      with acute postoperative pain].
AB  - Opioid analgesics buprenorphine, nubain, and morphine were used in 33 patients
      suffering from acute postoperative pain on days 1-3 after operations on the
      lungs, heart and main vessels, abdominal organs. Buprenorphine was used in dose
      0.01 mg/kg, nubain in dose 0.3 mg/kg, and morphine in dose 0.3 mg/kg. Effects of
      opioid analgesics on O2 consumption, carbon dioxide exhalation, minute
      respiration volume, and total energy metabolism were monitored. Effects of
      buprenorphine on metabolism and ventilation were the most manifest: it lead to
      reduction of metabolism by 26.2% and minute respiration volume by 36%. Nubain had
      no noticeable effect on metabolism or ventilation parameters. Morphine lead to
      moderately expressed changes in metabolism and ventilation reducing metabolism by
      12.5% and minute respiration volume by 10.3%.

PMID- 7802315
TI  - [New possibilities of the use of central adreno-positive preparations in
      anesthesiology].
AB  - New clinical findings demonstrate a high efficacy of clofelin (100-200 mcg
      epidurally) as a nonopiate analgesic at the pre-, intra-, and postoperative
      stages of anesthesiologic care. Prospects of using clofelin in combination with
      morphine are discussed, as is the use of guanfacine as an agent for prolonged
      analgesia in the postoperative period.

PMID- 7802314
TI  - [Suggestions concerning modification of traditional 3-stage schedule of drug
      therapy of chronic pain in incurable oncologic patients].

PMID- 7802316
TI  - [Neurogenic pain syndromes and their pathogenetic therapy].
AB  - Analgesic effects of morphine, clofelin, sirdalud, propranolol, and verapamil
      were studied in animals with the neurogenic painful syndrome induced by cutting
      the sciatic nerve and in patients with phantom painful syndrome after limb
      amputation. In animals with cut sciatic nerve morphine not only failed to prevent
      neurogenic pain, but was conducive to its increase. And, on the contrary,
      nontraditional analgesics clofelin, sirdalud, propranolol, and verapamil showed a
      high therapeutic efficacy both in experiments and in clinical trials. The results
      are discussed from the viewpoint of pathogenetic mechanisms of development of
      neurogenic painful syndromes.

PMID- 7802317
TI  - [Nonsteroid anti-inflammatory agents (acelysin) in postoperative analgesia and
      intensive care].
AB  - Efficacy of nonsteroid antiinflammatory drugs in the system of postoperative
      intensive care of patients to relieve postoperative pain, reduce the aftereffects
      of surgical injury to tissues, and thromboembolic complications is
      pathogenetically validated. A high efficacy of water-soluble acetylsalicylic
      acid, acelysin, in patients after extensive oncologic surgery is demonstrated.
      Acelysin had a good analgesic effect without side effects and permitted reducing
      the dose of opiates for postoperative analgesia by 3 times in comparison with the
      control group. Acelysin infusion in the immediate postoperative period reliably
      prevented thromboembolic complications and ruled out the necessity of resorting
      to heparin. Acelysin is regarded as a special nonopiate component of
      postoperative intensive care noticeably improving its efficacy.

PMID- 7802318
TI  - [Central electroanalgesia as a component of combined anesthesia in reconstructive
      microsurgery].
AB  - Efficacy of central analgesia and adequacy of anesthesiologic protection in
      operations making use of microsurgical techniques were analyzed by double blind
      method using the criterion 'requirement in narcotics' in 88 specially selected
      patients divided into 4 groups. Group 1 (n = 24) were patients operated on under
      electro-medicamentous anesthesia after Kastrubin-Kordyukov; group 2 (n = 21) were
      operated on under electro-medicamentous anesthesia after Limoges' technique
      modified by M.I. Kuzin et al.; group 3 consisted of 14 patients operated on under
      combined anesthesia based on NLA agents and simultaneous simulation of
      transcerebral electropulse exposure (placebo group); and group 4 (n = 29) were
      patients operated on under combined NLA anesthesia (controls). To assess the
      function of systems of adaptation to surgical trauma blood plasma levels of ACTH
      and cyclic nucleotides were measured at 7 stages of anesthesia.

PMID- 7802319
TI  - [Analgesic properties of different ligands of opioid receptors].

PMID- 7802320
TI  - [Prolonged sacral anesthesia with buprenorphine in combination with a local
      anesthetic in the treatment of chronic pain of oncologic patients with lesions of
      organs of the small pelvis].

PMID- 7802321
TI  - [Clinical use of tramadol in lithotripsy compared with buprenorphine].
AB  - The comparison was made of analgetic action of tramadol and
      buprenorphine+diazepam in extracorporeal impulse lithotripsy. Opiate agonist
      antagonist buprenorphine can provide high-quality analgesia in a drastic lowering
      of sHbO2. Nonnarcotic analgetic tramadol does not depress external respiration
      and provides adequate analgesia.

PMID- 7802323
TI  - [Use of clopheline in intensive care and anesthesiology].

PMID- 7802322
TI  - [First experience in the use of a new Russian narcotic analgesic prosidol in
      oncology].
AB  - Prosidol, a new Russian narcotic analgesic, was used in various dosage forms
      (buccal and oral tablets, injection solution) in 113 cancer patients for the
      treatment of chronic pain, as a component of total anesthesia, and for
      postoperative analgesia. The best results were attained with the universal
      noninvasive dosage form, buccal tablets, used for the treatment of chronic pain
      in incurable patients. Analgesic properties of buccal prosidol are close to those
      of tramadol, the drug is well tolerated by the patients and causes no grave side
      effects. As a drug for postoperative analgesia prosidol was highly effective in
      patients after extracavitary oncologic surgery and less effective after thoracal
      and abdominal interventions. As a component of total anesthesia prosidol is
      inferior to fentanyl and approximately similar to promedol. An advantage of
      prosidol is its highly effective universal noninvasive dosage form, buccal
      tablets, which may be used for rapid analgesia in any situation.

PMID- 7802324
TI  - [Current status of the treatment of chronic pain in oncological patients].

PMID- 7802326
TI  - Closing the loop with electronic publishing.

PMID- 7802327
TI  - Case report WI. Treatment of arch length deficiency in an adult male: the
      extraction of compromised molars rather than healthy premolars.

PMID- 7802325
TI  - [Analgesic effects of serotoninergic agents].

PMID- 7802328
TI  - Finite element-based cephalometric analysis.
AB  - The finite element method has proven to be a useful tool for morphometric
      analysis in craniofacial biology. However, few attempts have been made to adapt
      this method for routine use by clinicians. The CEFEA program incorporates the
      advanced features of the finite element method but bypasses the detailed
      understanding of the engineering and mathematics previously required to interpret
      results. The program uses the color graphics display of common personal computers
      to show size change, shape change, and angle of maximum change. These are
      pictured as colored triangles of clinically relevant regions between pre- and mid
      or posttreatment lateral headfilms. The program is designed to have features of
      interest in both clinical practice and research.

PMID- 7802330
TI  - A cephalometric evaluation of nonextraction cervical headgear treatment in Class
      II malocclusions.
AB  - The effects of orthodontic treatment with the use of the cervical pull facebow
      headgear in patients with Class II malocclusions were evaluated with special
      reference to the dentition, the maxillary complex, the mandible, and the facial
      profile. The records of 85 patients, with a mean age of 11.3 +/- 1.7 years, were
      selected from a sample of 125 patient records requested from the office of John
      S. Kloehn in Appleton, Wisconsin. Dr. Kloehn has used traditional cervical pull
      facebow therapy in his practice. Over 100 linear and angular cephalometric
      measurements were made from the pretreatment and posttreatment records. These
      measurements were used to evaluate growth and/or treatment changes. The treatment
      sample was divided by size of the pretreatment FMA, sex, and the age range in
      which treatment was started, i.e., prepubertal, circumpubertal, and postpubertal.
      Overall, the results showed that the changes were very close to what would occur
      as a result of normal growth in Class I individuals. The maxillary permanent
      first molars continued to progress forward, the maxilla continued to grow
      forward, and the cranial base showed very little change, if any. The mandibular
      plane angle did not increase appreciably with treatment, regardless of the size
      of the pretreatment mandibular plane angle. Very few significant differences were
      found between sexes, pretreatment age groups, or between groups based on
      pretreatment Frankfort mandibular plane angle.

PMID- 7802329
TI  - Comparisons of the dental arch changes in patients with Class II, division 1
      malocclusions: extraction vs nonextraction treatments.
AB  - Treatment and posttreatment changes in the dental arches of patients with Class
      II, division 1 malocclusions were evaluated. Half the patients (N = 46) were
      treated with a nonextraction approach; treatment for the other half (N = 45)
      included the extraction of four first premolars. The following parameters were
      measured in the maxillary and mandibular arches: arch width at the incisors,
      canines, second premolars and first permanent molars; anterior, posterior and
      total arch lengths; and total and anterior tooth size-arch length discrepancies.
      These parameters were measured pretreatment, immediately following orthodontic
      treatment and at least 2 years posttreatment. The findings indicate that the
      extraction of premolars significantly improves the discrepancy between the tooth
      size and arch length during treatment. Posttreatment both the extraction and
      nonextraction groups experienced an increase in tooth size-arch length
      discrepancies and a reduction in arch length. Extractions did not significantly
      alter the direction of the overall posttreatment trends for some parameters,
      e.g., intercanine width and tooth size-arch length discrepancies. On the other
      hand, the posttreatment trends for other parameters--such as intermolar width-
      were significantly different between the extraction and nonextraction groups. In
      general, the trends in the posttreatment changes were similar in males and
      females as well as in the maxillary and mandibular arches.

PMID- 7802331
TI  - Shape of the craniofacial complex in patients with Klinefelter syndrome.
AB  - The shape and size of the craniofacial complex in 35 adults with Klinefelter
      syndrome (47,XXY) were analyzed cephalometrically and compared with 60 control
      males. Twenty-four angular and 18 linear measurements were obtained for each
      subject. The results showed that the 47,XXY males were different from the
      controls in several areas of the craniofacial skeleton. Most of the differences
      were located in the cranial base and the cranial base angle (p < 0.02). The
      length of the maxillary base was greater (p < 0.05) and more prognathic (p <
      0.01) in the study group. The mandible was also longer and more prognathic (p <
      0.01).

PMID- 7802332
TI  - Effect of H3PO4 concentration on bond strength.
AB  - Prior to bonding, the enamel surface of the tooth is normally etched using a
      solution of 37%-50% phosphoric acid (H3PO4) for 60 seconds. The purpose of this
      study was to evaluate the tensile bond strength, debonding interface distribution
      and enamel surface detachment of various concentrations of H3PO4 solution, from
      2% to 80%, applied for 15 seconds. Statistically significant differences in bond
      strength were found among the various concentrations tested: concentrations in
      the 10% to 60% range produced greater bond strengths than both the weaker and
      stronger concentrations. The weaker the bond strength, the greater the debonding
      interface between resin and enamel. The greater the bond strength, the greater
      the debonding interface between the bracket and resin. Enamel detachment occurred
      as the H3PO4 concentration rose above 30%. To obtain greater bond strength and
      less enamel detachment, 10%-30% concentrations of phosphoric acid for 15 seconds
      etching are suggested for clinical bonding.

PMID- 7802333
TI  - Sealant and resin viscosity and their influence on the formation of resin tags.
AB  - The ability of resin to penetrate tooth enamel during orthodontic bonding may be
      affected by the viscosity of the resin and the presence of a sealant. Twenty-four
      extracted molars were randomly divided into six groups of four. Three resin
      viscosities were applied with and without sealant and resin tag formation was
      studied with a scanning electron microscope. Statistically larger resin tags
      resulted in the group using the more fluid composite resin (orthodontic Concise)
      in combination with the sealant, although the frequency, regularity and form of
      the tags did not differ significantly among the various viscosities.

PMID- 7802335
TI  - Thyroid administration to reduce root resorption.

PMID- 7802334
TI  - Thyroid function and root resorption.
AB  - The regulation of degradative activity such as phagocytosis and bone resorption
      in the periodontal region is greatly influenced by factors controlling general
      bone modeling. The purpose of this study was to determine if thyroxine has any
      influence on the occurrence of force-induced root resorption. Young male rats
      were divided into three groups: a group of normal rats, a control group in which
      appliances were placed, and an experimental group in which appliances were placed
      and I-thyroxine was administered (5 micrograms/kg bw for 12 days). Root
      resorptions were induced by orthodontic force on the maxillary incisors. Fewer
      force-induced root resorption lesions occurred in the thyroxine group than in the
      control group. Alkaline phosphatase activity in the thyroxine group was
      significantly different from the normal and control groups. Thus, the decrease of
      resorptive lesions in the thyroxine group seemed correlated to a change in the
      bone modeling process, especially as related to the resorption activity.

PMID- 7802336
TI  - [Practical advice concerning biological fluids for analysis of trace-elements].
AB  - Sampling conditions are of utmost importance for the determination of trace
      elements in biological fluids. However, many biologists still underevaluate this
      critical step. This reports deals with collection of biological fluids from a
      routine point of view: detailed and careful descriptions of the contaminating
      role of air and the general handling of specimens are given in a practical and
      critical manner. The main commercial systems, made about needles, catheters,
      tubes (open and evacuated systems) and anticoagulants are reviewed. Choices and
      elementary rules, applicable in a hospital setting, are proposed.

PMID- 7802337
TI  - Development of a solid/liquid extraction method for analysis of toxic drugs in
      serum using an automated liquid chromatograph: the Remedi.
AB  - The aim of this work was to develop a procedure for analysis of drugs in serum
      using a chromatographic apparatus marketed by the Bio-Rad company. This automated
      apparatus, the Remedi, can identify nearly 200 substances and metabolites in
      biological fluids. The method for pretreatment of serum recommended by the
      manufacturer is inefficient. We thus decided to develop and validate an
      extraction method for analysis of serum. Our method extends column life and
      improves the sensitivity of the Remedi for the detection of drugs. For
      psychotropic drugs, a study was carried out that enables a semi-quantitative
      evaluation of blood levels to be made. In addition, the sera of patients admitted
      to hospital for intentional drug overdosage were studied to compare the results
      obtained using the Remedi and Emit techniques, and also to compare these results
      with toxicological data obtained by questioning the patient and his immediate
      circle.

PMID- 7802338
TI  - Study of the mechanisms involved in hydroxocobalamin interference with
      determination of some biochemical parameters.
AB  - Hydroxocobalamin (OHCo), a red pigment used as an antidote in cyanide poisoning,
      interferes with determination of some biochemical parameters. Plasma pools were
      spiked with two concentrations of OHCo and eight parameters (CK, SGOT, SGPT, ALP,
      lactic acid, creatinine, glucose, bilirubin) were assayed using Dimension and Aca
      III automated analyzers (Du Pont Instruments). Two parameters were affected by
      the presence of OHCo: CK and bilirubin. This study documents the type of
      interferences, spectral or chemical, and its probable causes.

PMID- 7802339
TI  - [Plasma concentration of C-reactive protein in patients with high estrogen
      levels].
AB  - The monitoring of inflammatory activity in patients with a high level of estrogen
      is controversial because the significance of a raised estradiol level on C
      reactive protein (CRP) concentrations is a debated question. This prompted us to
      assay CRP by a sensitive Elisa in a sample of 30 patients with ovarian
      stimulation for in vitro fertilization, thus with high levels of estradiol. For
      15 of these women, six to nine plasma samples were analyzed allowing a kinetic
      study of plasma levels of CRP, estradiol and sex steroid-binding plasma protein
      (SBP). No significant correlation was found between the concentrations of
      estradiol and CRP for the 30 patients. In the kinetic study, as mean estradiol
      levels rose exponentially from 50 to 1400 ng/l between day 5 and 14, the CRP
      level tended to vary markedly from one patient to another and sometimes from day
      to day, but there was never any relation with estradiol level. Furthermore, CRP
      did not significantly modify the slope of the regression line between estradiol
      concentration and the day of the menstrual cycle. In contrast, the effect of
      estradiol on SBP was clear, which supports the absence of estradiol effect on CRP
      level.

PMID- 7802341
TI  - [Comparative and simultaneous evaluation of three automated counters in
      hematology].

PMID- 7802340
TI  - Characteristics of the antibiotic resistance plasmid in Salmonella typhi isolated
      in Tunis in 1990.
AB  - A multiresistant Salmonella typhi (S typhi, strain 302) was isolated from a blood
      culture of a patient in the Infectious Diseases department of Rabta Hospital in
      Tunis. The following tests were carried out: antibiotic susceptibility testing by
      the agar diffusion method; determination of the minimum inhibitory concentration
      against four beta-lactam antibiotics (amoxicillin, ceftriaxone, ceftazidime,
      imipenem), chloramphenicol, gentamicin, and amikacin by the agar dilution method;
      conjugation with E coli K12 for study of transferability of resistance markers;
      and electrophoresis of plasmid DNA extracts on agarose gel. S typhi 302 was
      resistant to amoxicillin, streptomycin, tetracycline, chloramphenicol, and
      sulfamide-trimethoprim, and this resistance was transferable in toto with a
      frequency of 10(-4). The MICs of amoxicillin and chloramphenicol were,
      respectively, 1024 (due to the production of TEM-1 beta-lactamase) and 256 mg/l.
      These resistance markers were carried by a plasmid of about 40 kb, similar to the
      Salmonella wien plasmid. The easy acquisition of a multiresistance plasmid by S
      typhi suggests that epidemiological monitoring of this serovar should be carried
      out.

PMID- 7802342
TI  - Distribution of beta-carotene in serum lipoprotein fractions separated by
      selective precipitation.

PMID- 7802343
TI  - [Evaluation of the Technicon DAX 48].

PMID- 7802344
TI  - International Federation of Clinical Chemistry (IFCC). Enzyme reference
      materials: their place in diagnostic enzymology.

PMID- 7802347
TI  - [Recent progress in the diagnosis of intestinal amebiasis. Contribution of
      molecular biology].
AB  - Only 10% of Entamoeba histolytica strains have been reported to have a pathogenic
      capacity. Theoretically and under certain conditions, confirming this estimation
      should limit the number and the cost of the treatments administered to the four
      hundred million asymptomatic carriers in the world. Several new routine tests
      which allow more accurate and easier diagnosis of intestinal amoebiasis and in
      particular the differential diagnosis between the pathogenic and nonpathogenic
      strains are or soon will be available. The practical interest of some of these
      new tests is limited by the problem of assessing parameters such as the stability
      in vivo and the nonpathogenic features of the nonpathogenic strains, the
      frequency of the association between pathogenic and nonpathogenic strains, the
      prevalence of pathogenic strains compared with the nonpathogenic strains, and the
      kinetics of the elimination of the parasitic forms. Even if these tests are
      assumed to be efficient, they cannot be regarded as absolutely reliable because
      of the complexity of the clinical disease.

PMID- 7802345
TI  - [Antiphospholipid antibodies].
AB  - The term 'antiphospholipids' (APL) refers to heterogeneous auto-antibodies,
      including anticardiolipins detected by immunological methods and lupus
      anticoagulants detected by clotting tests. APL are currently of considerable
      interest, both from a clinical and a biological point of view, since their
      presence is associated with thromboembolic events. In this review, the authors
      emphasize the diversity of the clinical settings where APL are diagnosed and
      investigate the relationship between APL and thrombosis. The heterogeneity of APL
      and the lack of standard techniques make their laboratory diagnosis difficult and
      require the use of various types of tests. Several pathogenic mechanisms, all
      related to a possible effect of APL on the antithrombotic functions of vascular
      endothelium, have been proposed: decrease in prostacyclin synthesis, induction of
      procoagulant activity, inhibition of the endothelial anticoagulant functions, and
      impairment of fibrinolysis. Given the heterogeneity of these antibodies, it is
      unlikely that a single mechanism can account for their prothrombotic effect.

PMID- 7802346
TI  - [Transfer of plasma cholesterol and atherosclerosis].
AB  - Transfer processes in plasma are determinant in cholesterol metabolism. In many
      species, including man, there is an alternative route for the disposal of
      cholesteryl esters (CE) in HDL via transfer to VLDL in exchange for triglycerides
      (TG), a process dependent on a hydrophobic 74 kDa glycoprotein called cholesteryl
      ester transfer protein (CETP). In vivo, cholesteryl esters transferred from HDL
      will contribute to LDL, to which VLDL is converted. Although the prevention of CE
      accumulation in HDL may enhance the ability of HDL to take up more cholesterol
      from tissues, high rates of transfer may also increase the risk for atheroma by
      increasing formation of atherogenic lipoproteins. Conversely, CE retained within
      HDL, if returned directly to the liver, would be expected to be beneficial.
      Moreover, in most conditions predisposing to atheroma, CETP activity is raised;
      whereas species with low or absent CETP activity are at low risk for
      atherosclerosis.

PMID- 7802348
TI  - [Cellular receptor of thrombin].
AB  - Thrombin is a serine protease able to evoke biological responses from a variety
      of cells, including platelets, endothelial cells, fibroblasts and smooth muscle
      cells. The structure of the thrombin receptor present in the human
      megakaryoblastic cell line and in hamster fibroblasts has recently been deduced
      by expression in the Xenopus laevis oocyte. The cloned receptor is a new member
      of the seven transmembrane domain receptor family that interacts with G proteins.
      A large amino-terminal extracellular extension has a cleavage site for thrombin
      (Leu Asp Pro Arg/Ser Phe Leu Leu,/representing the cleavage site). Thrombin
      cleaves at this site, unmasking a new amino terminus, that functions like a
      ligand, binding to an as yet undefined site and eliciting receptor activation.
      Peptides similar to a new amino terminus created after cleavage are able to mimic
      thrombin cellular effects. These agonist peptides are used to analyse the role of
      the cloned receptor in the thrombin-specific response.

PMID- 7802349
TI  - Evaluation of iodide deficiency in Togo using an optimized potentiometric method
      for iodide estimation in urine.
AB  - A pilot study was carried out in two Togolese localities (Gobe, Moretan) situated
      in an endemic goiter area. The aim of this work was to collect laboratory and
      nutritional data to assess and follow up campaigns against iodide deficiency.
      Ninety-seven urine samples were analysed. We studied the urinary excretion and
      the iodine concentration of important diet substances (water and salt) using an
      optimized potentiometric method. Mean values of urinary iodide/creatinine ratios
      (microgram/g) observed in the two Togolese localities were respectively 34.1 +/-
      6.3 in Gobe and 39.2 +/- 6.4 in Moretan. These low values differ significantly (P
      < 10(-9)) from the physiological values determined in Amiens, France (147.5 +/-
      56.3). The drinking water of the two localities showed a low iodide concentration
      (2 micrograms/l). The iodide concentration of cooking salts was also low (< 0.2
      mg/kg) compared with iodized salt used in France (11.2 +/- 0.2 mg/kg) These
      results show an iodide deficiency in both localities, probably due to the lack of
      iodide in the local diet. Iodide determination is specific, easy and inexpensive.
      It can be proposed for use in campaigns against goiters of nutritional origin.

PMID- 7802350
TI  - [Demonstration of the anti-lipid peroxidation effect of 3',5,7-trihydroxy-4'
      methoxy flavone rutinoside: in vitro study].
AB  - Diosmin (DI) 3'5,7-trihydroxy-4'-methoxy flavone rutinoside is a member of the
      flavonoid family, some of whom have antioxidant or free radical scavenger
      properties. Paw oedema induced by doxorubicin in rats is reduced by DI as
      observed by SAUVAIRE et al (1989). This suggests a free radical scavenger
      activity for DI. In this work we demonstrate that such activity is able to
      protect isolated human LDL from oxidation in vitro. The study of the
      electrophoretic mobility of oxidized LDL and of total-MDA values as
      lipoperoxidation-marker indicates an oxidation inhibiting effect higher than 70%
      for 0.16 mM DI in LDL mixtures containing 50 mM Cu2+ or 4.3 mU/ml xanthine
      oxidase and incubated during 20 and 6 hours respectively. Owing to the high level
      of the oxidizing conditions and the vitamin E (48 mM), vitamin A (1.4 mM) and
      beta-carotene (2.4 mM) content of the LDL mixtures, it is concluded that DI is
      clearly able to complement the antioxidant effect of isoprenoids which are
      naturally present in LDL mixtures.

PMID- 7802351
TI  - [Stability of alpha-tocopherol: pre-analytical conditions in its determination in
      blood samples].
AB  - Incomplete and controversial data exist concerning vitamin E or alpha-tocopherol
      stability in biological samples. Recent clinical interest in the protective
      function of alpha-tocopherol provided another reason for the setting-up of a
      multicenter study by the Societe Francaise de Biologie Clinique. Our purpose was
      to examine the effects on alpha-tocopherol stability, firstly, of collection and
      transportation of blood samples, and, secondly, of the temperature (-20 degrees C
      and -80 degrees C) and period of storage of serum or plasma. alpha-tocopherol was
      determined in serum or plasma by isocratic liquid chromatography with UV
      detection at 292 nm. Our results established that alpha-tocopherol was extremely
      stable in blood, serum or plasma over 8 hours without special handling conditions
      (light, temperature). Pools of serum or plasma were stable for at least 3 months
      at -20 degrees C and -80 degrees C. They are suitable for use in the quality
      control of alpha-tocopherol. On the other hand, in some samples, we observed
      great variability in the rate of alpha-tocopherol degradation. However, there was
      lesser degradation when these plasma samples were stored at -80 degrees C instead
      of -20 degrees C. We therefore do not advise storing serum or plasma for more
      than 1 month at -20 degrees C for more than 3 months at -80 degrees C. This
      latter temperature is recommended in epidemiological studies.

PMID- 7802352
TI  - Artificial intelligence within the chemical laboratory.
AB  - Various techniques within the area of artificial intelligence such as expert
      systems and neural networks may play a role during the problem-solving processes
      within the clinical biochemical laboratory. Neural network analysis provides a
      non-algorithmic approach to information processing, which results in the ability
      of the computer to form associations and to recognize patterns or classes among
      data. It belongs to the machine learning techniques which also include
      probabilistic techniques such as discriminant function analysis and logistic
      regression and information theoretical techniques. These techniques may be used
      to extract knowledge from example patients to optimize decision limits and
      identify clinically important laboratory quantities. An expert system may be
      defined as a computer program that can give advice in a well-defined area of
      expertise and is able to explain its reasoning. Declarative knowledge consists of
      statements about logical or empirical relationships between things. Expert
      systems typically separate declarative knowledge residing in a knowledge base
      from the inference engine: an algorithm that dynamically directs and controls the
      system when it searches its knowledge base. A tool is an expert system without a
      knowledge base. The developer of an expert system uses a tool by entering
      knowledge into the system. Many, if not the majority of problems encountered at
      the laboratory level are procedural. A problem is procedural if it is possible to
      write up a step-by-step description of the expert's work or if it can be
      represented by a decision tree. To solve problems of this type only small expert
      system tools and/or conventional programming are required.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7802354
TI  - Rapid test for the detection of dipyridamole-containing gallstones.

PMID- 7802353
TI  - [Perspectives of application of anti-CD4 antibodies in the treatment of
      autoimmune diseases].
AB  - Autoimmune diseases are a group of chronic inflammatory diseases which in some
      patients can be associated with autoantibodies generating tissue lesions. The
      cytotoxic activity and cytokine production by T lymphocytes is most often
      responsible for the pathogenic effect. Several clinical trials using monoclonal
      antibodies against T lymphocytes have been conducted either to evaluate the
      immunosuppressive activity of the antibody or to gain new insight into the
      mechanisms involved in these diseases. The most promising antibodies are directed
      against the CD4 antigen because they can induce a specific tolerance in animals.
      The preliminary results of these clinical studies are promising as demonstrated
      by clinical and laboratory improvement and lack of major side effects. Some
      antibodies induce circulating CD4+ T cell destruction with sometimes a prolonged
      depletion of CD4+ T cells while others exert their effect without any decrease in
      CD4+ lymphocytes. No predictive factor of therapeutic efficacy has yet been
      identified, but the preliminary results have indicated the major objectives for
      future trials as well as the laboratory and clinical parameters to be used as end
      points.

PMID- 7802355
TI  - Comparative study of the differential white blood cell count using three
      automated analyzers: Coulter STKS, Sysmex NE 8000 and Technicon H-1.

PMID- 7802356
TI  - International Federation of Clinical Chemistry (IFCC): systematic top-down
      approach to clinical chemistry.
AB  - This paper introduces a systematic approach to organizing the discipline of
      clinical chemistry. The approach is called a top-down, systems approach because
      it starts at the top with the most general concepts and works down through less
      general concepts to the most specific details and techniques. The hypothesis is
      that the discipline can be organized into hierarchical levels of functional
      processes and operational approaches to those processes. The functional processes
      represent what clinical scientists do; the operational approaches represent how
      they do it. Because functional processes change little, if at all, with time,
      they are use to develop a stable infrastructure or framework for the discipline.
      That infrastructure is then used to organize and understand operational
      approaches that tend to change rapidly with time in response to technological
      advances. This paper begins with the most general functional processes and then
      uses selected examples of the more general functions to illustrate lower
      hierarchical levels of functional processes and operational approaches.

PMID- 7802358
TI  - Internal carotid artery dissection associated with scuba diving.
AB  - A 52-year-old man presented to the emergency department with dysphasia and a
      headache after scuba diving. He was treated initially for decompression sickness.
      Subsequent workup revealed bilateral internal carotid artery dissection. The risk
      factors, presenting symptoms, diagnosis, and treatment of internal carotid artery
      dissection are reviewed. The importance of considering unusual causes of
      neurologic deficits after scuba diving is emphasized.

PMID- 7802357
TI  - A rapid diagnostic and treatment center for patients with chest pain in the
      emergency department.
AB  - STUDY OBJECTIVE: To evaluate a comprehensive diagnostic 9-hour evaluation (Heart
      ER Program) for patients with possible acute ischemic coronary syndromes. DESIGN:
      Retrospective review of consecutive patients. SETTING: Urban tertiary care
      emergency department. PARTICIPANTS: A total of 1,010 patients with symptoms
      suggestive of acute ischemic coronary syndrome was enrolled in the Heart ER
      Program over the first 32 months of operation. Patients with history of coronary
      artery disease, hemodynamic instability, acute ST-segment elevation or depression
      of more than 1 mm, or a clinical syndrome consistent with unstable angina were
      directly admitted to the hospital. INTERVENTION: Patients underwent serial
      testing for creatine kinase (CK-MB) on presentation to the Heart ER and 3, 6, and
      9 hours later with continuous 12-lead ECGs/serial ST-segment trend monitoring for
      9 hours. Two-dimensional echocardiography and graded exercise testing were
      performed in the ED after the 9-hour evaluation period. RESULTS: Of 1,010
      patients, 829 (82.1%) were released home from the ED; 153 (15.1%) required
      admission for further cardiac evaluation. Fifty-two of 153 (33.9%) admitted
      patients were found to have a cardiac cause for their symptoms; 43 had acute
      ischemic coronary syndromes (12, acute myocardial infarction; 31, angina or
      unstable angina). CONCLUSION: The Heart ER program provides an effective method
      for evaluating low- to moderate-risk patients with possible acute ischemic
      coronary syndrome in the ED setting.

PMID- 7802359
TI  - Drive-by shootings.
AB  - Gang violence has reached epidemic proportions in Los Angeles and is occurring
      with increasing frequency in many other US cities. Gang members and innocent
      bystanders often suffer severe and sometimes fatal injuries in drive-by
      shootings. We present the case of one such innocent victim and discuss the
      personal and societal ramifications of drive-by shootings.

PMID- 7802360
TI  - Varicella: pediatric genital/rectal vesicular lesions of unclear origin.
AB  - Three children who presented with localized vesicular rash in the diaper area
      were found to have primary varicella-zoster infections. Primary varicella can
      closely mimic genital herpes simplex virus (HSV 1 or 2), which may be an
      indicator of sexual abuse. To avoid unfounded investigation for sexual abuse,
      primary varicella-zoster infection must be included in the differential
      diagnosis. Direct fluorescent antibody testing is a sensitive and specific
      diagnostic test that can be used to distinguish HSV 1 or 2 from varicella-zoster.

PMID- 7802361
TI  - Ectopic attitude.

PMID- 7802362
TI  - Acetaminophen overdose.

PMID- 7802363
TI  - Verapamil toxicity.

PMID- 7802364
TI  - Correlation of CO2 measurement methods.

PMID- 7802365
TI  - Determination of normal ear temperature with an infrared emission detection
      thermometer.
AB  - STUDY OBJECTIVE: To determine normal body temperature with an infrared emission
      detection ear thermometer. DESIGN: Cross-sectional convenience sample. SETTING:
      Four acute and long-term health care facilities. PARTICIPANTS: Subjects who
      denied recent potentially febrile illness and ingestion of medications affecting
      normal body temperature. RESULTS: Two thousand four hundred forty-seven subjects
      aged 12 hours to 103 years were enrolled. Ear temperatures were normally
      distributed for each of eight age groups. There were differences in mean
      temperature among different age groups (P < .001, by ANOVA) and a striking cutoff
      at adolescence; the mean temperature for children aged 3 days to 10 years was
      36.78 +/- 0.47 degrees C, as compared to 36.51 +/- 0.46 degrees C for subjects 11
      years and older (P < .001, by t test). Temperatures were higher in female
      subjects and showed the characteristic diurnal variation of normal body
      temperature in five subjects studied longitudinally. The reproducibility of the
      ear thermometer was better than that of a commonly used electronic thermometer at
      the oral and axillary sites. CONCLUSION: The infrared emission detection ear
      thermometer is an accurate means of assessing normal body temperature without
      using corrective offsets to estimate temperature at other body sites. On the
      basis of these data, the 95th percentile for infrared emission detection
      temperature in children younger than 11 years old was 37.6 degrees C. The 99th
      percentile was 37.9 degrees C for children younger than 11 years old and 37.6
      degrees C for people 11 years or older. Because only 1% of normal people have an
      infrared emission detection temperature higher than these values, these may
      represent appropriate cutoffs for fever screening using this device.

PMID- 7802367
TI  - Contribution of routine pulse oximetry to evaluation and management of patients
      with respiratory illness in a pediatric emergency department.
AB  - STUDY OBJECTIVE: To determine whether routine pulse oximetry in a pediatric
      emergency department can be used to identify patients with a low oxygen
      saturation (SaO2) that is unexpected on the basis of clinical evaluation. DESIGN:
      Prospective comparison of blinded, clinical evaluation by physicians with
      subsequent pulse oximetry readings. SETTING: Pediatric ED in an urban, university
      medical center. PARTICIPANTS: A convenience sample of 368 patients presenting to
      the pediatric ED with respiratory illnesses. METHODS: The history, physical
      examination, pediatric ED management, and therapy were recorded. Based on
      clinical assessment, the physician was asked whether the patient had a low SaO2
      (< or = 92%). Room-air pulse oximetry was then obtained, with subsequent
      treatment and management plans recorded. RESULTS: Clinical assessment had a
      sensitivity of 33%, specificity of 86%, negative predictive value of 85%, and
      positive predictive value of 35% for detecting children with low SaO2. Unexpected
      low SaO2 usually led to a change in patient management or disposition.
      CONCLUSION: Clinical evaluation in a pediatric ED does not screen adequately for
      the detection of hypoxemia and should be supplemented by routine pulse oximetry
      in all patients with respiratory findings.

PMID- 7802368
TI  - Tympanic membrane thermometry in the care of out-of-hospital patients.
AB  - STUDY OBJECTIVES: To determine the effectiveness of tympanic membrane (TM)
      thermometry in the out-of-hospital setting and to characterize the patients with
      abnormal out-of-hospital temperatures. DESIGN: Prospective, randomized, single
      month study. SETTING: Inner city. PARTICIPANTS: Subjects transported by ambulance
      for whom consent was obtainable. RESULTS: TM probes set to rectal equivalent were
      assigned to three of the ambulance units of the local health department on
      randomly selected shifts during August 1992, one half at night and one half
      during the day. Simultaneous left and right ear temperatures at the scene and at
      the hospital, ambient temperatures, and patient's hospital temperatures were
      recorded. Other data recorded included each patient's mental status, activity
      level, and environment temperature. Paramedics noted whether they suspected a
      temperature problem before using the probe and whether any treatment was directed
      toward the patient's temperature. Regression, bias analysis, and chi 2 testing
      were performed; P was considered significant if it was less than .05. Right and
      left ear TM temperatures were correlated both at the scene and at the hospital (r
      = .91 and .92, respectively). TM temperatures and hospital temperatures were also
      correlated (r = .83 for right ear and .78 for left ear). Evaluation of agreement
      indicated that TM and hospital methods were equal, with a bias of -0.55 degrees F
      for oral and +0.66 degrees F for rectal temperatures. Thirty-two subjects (17%)
      were hyperthermic at the scene; of these, 9 of 32 (28%) were suspected before use
      of the probe. The paramedics initially treated 5 of the 9 suspected to have a
      temperature-related problem before using the probe and none of the 23 who were
      not suspected before using the probe (chi 2, P < .001). CONCLUSION: The TM probe
      functioned well despite a month of vigorous handling. Temperature correlation
      with the gold standard and between ears was acceptable in this setting. Presence
      of the probe did not help with the management of hyperthermic patients in this
      study.

PMID- 7802369
TI  - End-tidal carbon dioxide during out-of-hospital cardiac arrest resuscitation:
      comparison of active compression-decompression and standard CPR.
AB  - STUDY OBJECTIVES: To compare the maximal end-tidal carbon dioxide pressure (ETCO2
      peak) values obtained during standard (S-CPR) and active compression
      decompression CPR (ACD-CPR) during prolonged resuscitation in out-of-hospital
      cardiac arrest. DESIGN: Prospective, randomized crossover study. SETTING: City
      with a population of 3.5 million, served by an emergency medical service system
      providing advanced cardiac life support. PARTICIPANTS: Patients with nontraumatic
      out-of-hospital cardiac arrest. INTERVENTIONS: Patients were randomly assigned to
      receive first, for a period of 3 minutes, either ACD-CPR or S-CPR; then the two
      methods were alternated. ETCO2 was continuously monitored and computed.
      MEASUREMENTS AND RESULTS: Sixteen patients (48 +/- 20 years old) were included;
      in 12, return of spontaneous circulation was achieved, and 5 were admitted alive
      to the hospital. A statistically significant increase in ETCO2 peak was obtained
      with ACD-CPR (27.6 +/- 3 mm Hg) compared with S-CPR (15.6 +/- 2.2 mm Hg). No
      major adverse effect possibly related to ACD-CPR was observed. CONCLUSION: This
      prospective study suggests that ACD-CPR may improve cardiac output compared with
      S-CPR.

PMID- 7802366
TI  - Reliability of infrared tympanic thermometry in the detection of rectal fever in
      children.
AB  - STUDY OBJECTIVE: Recently published clinical guidelines for the management of
      febrile children are based on studies that used rectal temperature data to
      stratify the risk of bacteremia and septic complications. Appropriate management
      decisions rely on accurate detection and categorization of fever. Accordingly,
      this study compared the newer infrared tympanic thermometry (ITT) to rectal
      thermometry in this regard. DESIGN: Prospective observational study. SETTING:
      Urban teaching hospital ED with annual census of 60,000. PARTICIPANTS:
      Consecutive children 6 months to 6 years old who had rectal temperatures
      measured. INTERVENTIONS: Triage nurses recorded rectal temperatures and bilateral
      ITT temperatures. Temperatures were correlated by Pearson correlation
      coefficients and compared using paired t tests with significance set at P < .01.
      Children were categorized by degree of fever using rectal temperature (afebrile,
      less than 100.4 degrees F; low fever, 100.4 to 102.9 degrees F; and high fever,
      more than 102.9 degrees F), and the accuracy of ITT in detecting fever and high
      fever was determined. RESULTS: Three hundred seventy patients were enrolled in
      the study. The mean age was 18.4 +/- 11.3 months; boys comprised 56% of patients.
      The mean temperatures were rectal, 101.0 +/- 2.0 degrees F; right tympanic
      membrane, 100.4 +/- 1.9 degrees F; and left tympanic membrane, 100.3 +/- 1.9
      degrees F. The tympanic membrane temperatures were significantly lower than
      rectal readings (P << .001 for both right and left versus rectal). Rectal
      temperatures showed good correlation with both right and left tympanic membrane
      temperatures (r = .83 and .85, respectively). ITT was 76% sensitive and 92%
      specific in detecting fever of 100.4 degrees F or more (positive predictive
      value, 0.92; negative predictive value, 0.76). In the detection of high fever,
      ITT was only 57% sensitive but 98% specific (positive predictive value, 0.90;
      negative predictive value, 0.90). Rectal and TM temperatures differed by at least
      0.5 degree F in 70% of the patients, 1.0 degree F in 41%, 2.0 degrees F in 12%,
      and 3.0 degrees F in 3%. CONCLUSION: Despite the statistical correlation between
      ITT and rectal temperatures, the modalities may yield significantly different
      temperatures. The poor sensitivity of ITT in detecting fever and high fever may
      result in clinically important miscategorizations of individual patients. Current
      clinical management that is based on the presence and height of fever may be
      adversely affected if ITT is used.

PMID- 7802370
TI  - Physician compliance with advanced cardiac life support guidelines.
AB  - STUDY OBJECTIVE: To determine compliance with advanced cardiac life support
      (ACLS) guidelines among ACLS-certified and non-ACLS-certified physicians. DESIGN:
      Retrospective review of consecutive cardiac arrests between July 1989 and June
      1990, including assessment of the resuscitation leaders' ACLS certification.
      SETTING AND PARTICIPANTS: All nontraumatic prehospital and hospital cardiac
      arrests in a rural university hospital. RESULTS: Two hundred seven arrests were
      studied for a total of 436 rhythms with a maximum of 4 rhythms per arrest. There
      were 78 resuscitations (36.3%) with return of spontaneous circulation. A total of
      2,038 interventions were recorded for all rhythms, with 1,320 (64.8%) compliant
      with ACLS guidelines compared with 718 (35.2%) deviations. Synchronized
      cardioversion, calcium chloride and sodium bicarbonate were used with
      significantly higher noncompliance. Ventricular fibrillation had significantly
      higher mean rhythm deviation scores, whereas scores were significantly lower for
      sinus rhythm and stable bradycardia (P < .003). Resuscitations led by ACLS
      certified and non-ACLS-certified physicians were compared for mean number of
      deviations per resuscitation attempt, and no differences were found.
      Resuscitations with return of spontaneous circulation were compared with
      unsuccessful resuscitations, and there was no difference between groups in
      controlled deviation scores. No differences could be found between ACLS-certified
      and non-ACLS-certified physicians for return of spontaneous circulation and
      survival-to-discharge rates. CONCLUSION: Despite biannual ACLS training of all
      medical residents and ICU nurses, noncompliance with ACLS guidelines was noted in
      35.2% of treatments. We found no correlation between ACLS certification and ACLS
      guideline compliance.

PMID- 7802371
TI  - Prognosis among survivors of prehospital cardiac arrest.
AB  - STUDY OBJECTIVE: To describe the prognosis in consecutive patients discharged
      from hospital after prehospital cardiac arrest. PATIENTS: All patients in the
      community of Goteborg who were discharged from hospital after out-of-hospital
      cardiac arrest between 1981 and 1991. RESULTS: Two hundred forty-three patients
      were discharged from hospital during the observation period, of whom 80%
      initially experienced ventricular fibrillation. Among patients discharged, 21%
      died during the first year; after 10 years, 82% had died. Age, sex, previous
      history of cardiovascular disease, circumstances at the time of cardiac arrest,
      complications during hospitalization, and discharge medications were assessed as
      predictors of 1-year mortality. Independent predictors of death during follow-up
      were history of myocardial infarction (P < .001), no prescription of beta
      blockers at discharge (P < .01), age (P < .05), and cerebral performance category
      (CPC) at discharge (P < .05). CONCLUSION: Among patients who survived out-of
      hospital cardiac arrest, one of five died during the first year and one of five
      survived 10 years after discharge. Prognosis was associated with a history of
      myocardial infarction, prescription of beta-blockers at discharge, age, and CPC
      at discharge.

PMID- 7802372
TI  - Comparison of prehospital monomorphic and polymorphic ventricular tachycardia:
      prevalence, response to therapy, and outcome.
AB  - OBJECTIVE: Monomorphic ventricular tachycardia (MVT) is the most common form of
      prehospital ventricular tachycardia (VT). Recent literature suggests that
      polymorphic ventricular tachycardia (PVT) is more common during cardiopulmonary
      arrest than previously thought but responds poorly to advanced cardiac life
      support (ACLS) therapy. We undertook this study to determine the prevalence,
      response to therapy, and outcome of both MVT and PVT in the prehospital sudden
      cardiac death victim. DESIGN: Retrospective prehospital chart review from 1987 to
      1991. SETTING: Municipal, fire department-based, multitiered emergency medical
      system serving a population of approximately one million. PARTICIPANTS: Adult
      patients older than 18 years experiencing prehospital, nontraumatic
      cardiopulmonary arrest with VT occurring at any time during the resuscitation. VT
      was defined as PVT if the QRS-complex configuration was not stable when viewed in
      a single electrocardiographic lead (ie, episodic changing of the QRS-complex
      electrical axis, amplitude, or both or the presence of more than two QRS-complex
      morphologies). Outcome was defined in terms of both the presence or absence of
      spontaneous circulation at the end of the prehospital phase of care and ultimate
      outcome (survival to hospital discharge or death). Four hundred seventy-six
      patients met entry criteria; 37 patients were excluded because of incomplete
      medical records, and 439 patients were used for data analysis. INTERVENTIONS:
      ACLS therapy based on the 1987 American Heart Association guidelines. RESULTS:
      MVT occurred in 323 patients (73.6%), with 119 (36.8%) showing return of
      spontaneous circulation (ROSC) in the prehospital setting; 35 MVT patients
      (10.8%) survived to hospital discharge. PVT occurred in 116 patients (26.4%),
      with 48 (41.4%) showing ROSC in the prehospital setting; 15 PVT patients (12.9%)
      survived to hospital discharge. The use of ACLS therapy (defibrillation,
      endotracheal intubation, medication usage) between the two rhythm groups was not
      statistically different. The P values for ROSC, ultimate outcome, and use of ACLS
      therapy were all not significant. CONCLUSION: We conclude that PVT is a common
      rhythm occurring in prehospital cardiopulmonary arrest that responds as well as
      MVT to ACLS therapy. Until prospective data are available, standard ACLS therapy
      should be used in all forms of prehospital VT occurring during cardiopulmonary
      arrest.

PMID- 7802373
TI  - Comprehension of discharge instructions by patients in an urban emergency
      department.
AB  - STUDY OBJECTIVE: To assess patients' comprehension of their emergency department
      discharge instructions and to determine if inner-city patients' literacy levels
      are adequate to comprehend written discharge instructions. DESIGN: Prospective,
      observational study. SETTING: The ED of an inner-city university hospital.
      PARTICIPANTS: Two hundred seventeen patients consecutively discharged from the ED
      during 12 separate time slots. INTERVENTIONS: Patients were interviewed after
      discharge from the ED and asked to state their diagnosis, medication
      instructions, and follow-up instructions. Comparisons between patient recall and
      instructions as written in the chart were assessed by independent raters and
      scored from poor to excellent. Patients were administered a standardized test of
      reading ability. RESULTS: Overall comprehension rates were judged to be good,
      although 23% of patients exhibited no understanding of at least one component of
      their discharge instructions. Mean reading ability of the patients was at the
      sixth-grade level. The ED's printed discharge instructions were written at an
      11th-grade reading level. Patients with low literacy scores were more likely to
      have poor comprehension of instructions. CONCLUSION: Overall comprehension rates
      in this population were good despite the fact that ED instruction sheets were
      written at an inappropriately high reading level. Verbal instructions given by
      the discharging physician likely have a significant effect on patients'
      comprehension of instructions.

PMID- 7802374
TI  - Critical, acutely poisoned patients treated with continuous arteriovenous
      hemoperfusion in the emergency department.
AB  - STUDY OBJECTIVE: To investigate the efficiency of a new non-pump hemoperfusion
      technique, continuous arteriovenous hemoperfusion, in the treatment of critical,
      acutely poisoned patients. SETTING: Emergency department of a general hospital.
      PARTICIPANTS: Acutely poisoned patients who failed to respond to intensive
      supportive treatment and needed hemoperfusion therapy. INTERVENTIONS: All
      patients received continuous arteriovenous hemoperfusion therapy for 4 to 8
      hours. Toxicant clearances were determined by obtaining serial theophylline and
      phenobarbital levels every 2 hours before, during, and after continuous
      arteriovenous hemoperfusion. Platelet counts, whole-blood activated clotting
      time, and vital signs were monitored. RESULTS: The clinical condition of these
      patients improved rapidly after continuous arteriovenous hemoperfusion was
      started. The treatments were performed easily, and no significant complications
      occurred. The clearances of theophylline and phenobarbital were 192.79 +/- 1.55
      mL/min and 290.25 +/- 25.33 mL/min, respectively, similar to those of
      conventional hemoperfusion. CONCLUSION: Continuous arteriovenous hemoperfusion is
      a simple, safe, effective, and less costly alternative to conventional
      hemoperfusion, especially in the EDs of hospitals without hemoperfusion
      facilities immediately available.

PMID- 7802375
TI  - A survey of wellness issues in emergency medicine (Part I).

PMID- 7802376
TI  - Don't ask, don't tell: practicing minimally invasive resuscitation techniques on
      the newly dead.

PMID- 7802377
TI  - Failure of a chest pain clinical policy to modify physician evaluation and
      management.
AB  - STUDY OBJECTIVE: To assess the effectiveness of a specific, targeted clinical
      policy regarding the evaluation of nontraumatic chest pain in the emergency
      department (ED) to modify physician evaluation and management. DESIGN:
      Retrospective, blinded chart review. SETTING: Twelve metropolitan EDs.
      PARTICIPANTS: All males older than 35 years and females older than 45 years who
      presented with nontraumatic chest pain during one of the two study periods--1
      year before (1989) or 1 year after (1991) dissemination of the American College
      of Emergency Physicians' (ACEP) chest pain clinical policy. MEASUREMENTS:
      Physician's compliance with various documentation rules regarding history and
      physical examination were compared between the two periods with chi 2 analysis.
      Fisher's exact test was used when any one cell value was less than five. The
      physician's compliance with the rules and guidelines of management (Actions) were
      compared between the two periods with chi 2 analysis. RESULTS: Rates of
      compliance for 1989 and 1991 were as follows: history documentation, 368 (82%)
      vs. 255 (78%) (P = .22); physical examination documentation, 397 (88%) vs. 287
      (88%) (P = .94); Action rules, 292 (65%) vs. 208 (64%) (P = .76); and Action
      guidelines, 247 (55%) vs. 172 (53%) (P = .55). CONCLUSION: We conclude that the
      dissemination of the ACEP chest pain clinical policy has not significantly
      modified the behavior of our metropolitan area emergency physicians regarding the
      evaluation and management of patients who present to the ED with a chief
      complaint of nontraumatic chest pain.

PMID- 7802378
TI  - Law versus life: the ethical imperative to practice and teach using the newly
      dead emergency department patient.

PMID- 7802379
TI  - The changing paradigm of acute heart attack prevention in the emergency
      department: a futuristic viewpoint?

PMID- 7802380
TI  - What's hot and what's not: the gold standard for thermometry in emergency
      medicine.

PMID- 7802381
TI  - Bioethics and health policy section: practicing procedures on the newly dead.

PMID- 7802382
TI  - Camera speeds for optoelectronic assessment of stride-timing characteristics in
      horses at the trot.
AB  - Quantitated locomotion analysis is increasingly being used during assessment and
      treatment of gait disorders in human beings. Locomotion analysis is also thought
      to have potential for enhancing the assessment of lameness in horses.
      Availability of high-speed video recording systems has simplified the process of
      quantitated locomotion analysis; however, the high cost of such systems has
      limited their use for routine clinical assessment in horses. The temporal
      resolution of 500- to 1,000-images/s (Hz) recording systems is beyond what has
      been considered necessary for precise quantitation of short-duration events in
      horses at the trot; however, it is uncertain whether the temporal resolution of
      more economical 60-Hz recording systems is adequate. To determine whether a
      recording rate of 60 Hz is satisfactory for assessment of stride-timing values in
      horses at the trot, the stride-timing values calculated from 60-Hz recordings
      were compared with those calculated from 1,000-Hz recordings that had been
      simultaneously made for 5 horses trotting on a horizontal treadmill at a speed of
      3.0 m/s. The left forefoot of each horse was fitted with an instrumented
      horseshoe that illuminated and quenched light-emitting diodes (LED) in view of
      both cameras precisely at toe contact, heel contact, heel lift, and toe lift. The
      exact pattern and timing of foot placement and lift was referenced by the
      illumination pattern of the LED. Recordings of 10 consecutive strides were
      reviewed, image by image for each horse, and the elapsed time at each important
      stride event was tabulated.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7802383
TI  - Effects of chemical restraint on the endoscopic appearance of laryngeal and
      pharyngeal anatomy and sensation in adult cattle.
AB  - Effects of 2 drugs commonly used for chemical restraint of cattle were evaluated
      for their effect on laryngeal and pharyngeal anatomy, function, and response to
      stimuli. Eighteen adult Jersey cows, free of respiratory tract disease, were
      studied. Cows were assigned at random to 1 of 3 treatment groups. Endoscopic
      evaluations were performed before and at a predetermined time interval after
      administration of each drug. Responses to stimuli were evaluated by stimulating 7
      preselected sites (epiglottis, left and right arytenoid cartilages, left and
      right vocal folds, and left and right dorsolateral pharyngeal walls) with a
      closed, transendoscopic biopsy probe. Xylazine HCl (0.05 mg/kg of body weight,
      i.v.) was administered to group-1 cows (n = 6), and endoscopy was repeated 5
      minutes after administration of the drug. Xylazine (0.07 mg/kg, i.v.) was
      administered to group-2 cows (n = 6), and endoscopy was repeated 5 minutes after
      administration of the drug. Acepromazine maleate (0.035 mg/kg, i.v.) was
      administered to group-3 cows (n = 6), and endoscopy was repeated 10 minutes after
      administration of the drug. Responses to stimuli were scored as brisk (0),
      moderate (1), slow (2), and absent (3). Scores for responses to stimuli were
      compared, using the Wilcoxon signed-rank test for data within groups, and a
      general linear models procedure, using the Kruskal-Wallis test between groups.
      Interobserver agreement rates were generated for each group. A value of P < 0.05
      was considered significant. Xylazine profoundly changed laryngeal sensitivity and
      function at both dosages. The corniculate processes of the arytenoid cartilages
      were observed to be in a markedly adducted position after sedation.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7802384
TI  - Influence of age, breed, and stage of pregnancy on hepatic ultrasonographic
      findings in cows.
AB  - Influence of age, breed, and stage of pregnancy on hepatic ultrasonographic
      findings of cows was determined. In addition, the relation between body weight,
      height at the withers, milk production, and the measurements determined via
      ultrasonography was investigated. The liver of 186 cows was examined
      ultrasonographically. The cows comprised Swiss Braunvieh, Simmental, and Holstein
      breeds, and age ranged from 2.5 to 11.5 years. The ultrasonographic findings of
      the liver, gallbladder, caudal vena cava, and portal vein were described, and the
      position, size, thickness, and distal angle of the liver were determined. In
      addition, the position and diameter of the caudal vena cava and portal vein were
      determined. There was no significant difference between any of the variables
      determined and breed or age. Therefore, measurements for the 3 breeds and for the
      various ages were summarized into 1 group. There were significant correlations
      between body weight, milk production, and size and thickness of the liver. In 3
      pregnant cows, the liver was examined ultrasonographically 8 times during the
      course of pregnancy. Positive correlation was detected between stage of pregnancy
      and diameter of the caudal vena cava. There was a negative correlation between
      stage of pregnancy and diameter of the portal vein. In 23 cows, the
      ultrasonographically determined measurements of the liver were compared with
      those determined at slaughter. Weight of the liver correlated well to thickness
      of the liver determined via ultrasonography.

PMID- 7802385
TI  - Amplification of strains of bovine herpesvirus 1 by use of polymerase chain
      reaction with primers in the thymidine kinase region.
AB  - A primer pair was designed from the published nucleotide sequence of the coding
      region of the bovine herpesvirus 1 (BHV-1) thymidine kinase (tk) gene for use in
      detection of the virus by use of polymerase chain reaction (PCR) amplification of
      12 BHV-1 strains (3 ATCC and 9 local isolates). A tk deletion mutant BHV-1, and 2
      BHV-4 strains from ATCC were used as negative controls. One strain each of feline
      herpes-virus, equine herpesvirus, and bovine adenovirus, and 2 noninoculated
      bovine cultured cells--bovine fetal testis and Madin-Darby bovine kidney--also
      were examined to verify specificity of the primers. A PCR product, 183 bp long,
      was detected by ethidium bromide staining after agarose gel electrophoresis, when
      purified DNA from cell cultures infected with BHV-1 strain LA was used as
      template. Specificity of the PCR product was confirmed by restriction digestion
      with Sac II enzyme and Southern blot hybridization. Amplification was detected by
      ethidium bromide staining of agarose gels and/or Southern blot hybridization with
      the radiolabeled PCR product of the LA strain in similarly prepared DNA templates
      of 5 other BHV-1 strains, 2 obtained from ATCC and 3 of the 9 local isolates. In
      a modified PCR protocol, using virus suspensions treated with a nucleic acid
      releasing cocktail, substantial amplification was obtained for the 3 BHV-1
      strains from ATCC and for all 9 local bovine herpesvirus field isolates.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7802386
TI  - Evaluation of an enzyme-linked immunosorbent assay that uses the 41-kd flagellin
      as the antigen for detection of antibodies to Borrelia burgdorferi in cattle.
AB  - An ELISA was developed to detect antibodies to the 41-kd flagellin (P41) of
      Borrelia burgdorferi in serum obtained from cattle. Absorption studies,
      immunoblot analysis, immunoelectron microscopy, and correlation of results of the
      P41-ELISA and the P39-ELISA as well as measurement of the antibody to P41 in
      calves challenge-exposed with Borrelia theileri were used to assess the
      specificity of the P41-ELISA. Antigens derived from Escherichia coli, Leptospira
      interrogans serovar hardjo, and B burgdorferi were used for absorption studies
      and immunoblot analysis. Antibodies to P41 of B burgdorferi cross-reacted with
      antigens of E coli, but were not cross-reactive with L hardjo. A value 3 SD
      higher than the mean of the negative-control population of cattle was defined as
      the minimum value (cutoff value) for a positive result by the P41-ELISA. Use of
      this value for classification of test results reduced the predicted rate of false
      positive results attributable to E coli cross-reactivity to 1%. Immunoblot
      analysis revealed that test-positive serum from cattle reacted mainly with 41-,
      39-, 34-, and 31-kd proteins of B burgdorferi, as well as several smaller
      proteins. Immunoelectron microscopy revealed that serum from cattle that was test
      positive by the P41-ELISA bound to the flagellin and outer membrane of B
      burgdorferi. Results of absorption studies, immunoblot analysis, and
      immunoelectron microscopy were correlated and indicated that serum from cattle
      that was test-positive by P41-ELISA had stronger reactivity to B burgdorferi
      antigens than to antigens of E coli or L hardjo.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7802387
TI  - Radiographic geometric variation of equine long bones.
AB  - As more sophisticated research is performed to refine fracture fixation
      techniques for horses, it is important that normal values for the geometric
      properties of the bones of the appendicular skeleton be determined and that
      suitable controls be available. We evaluated the geometric properties of total
      bone width, cortical bone width, and medullary canal/trabecular bone width
      measured from 2 radiographic projections of equine long bones (humerus, radius,
      third metacarpal bone, femur, tibia, and third metatarsal bone) obtained from a
      general population of horses. Measurements were performed on slices separated by
      intervals equal to 5% of the bone's length. Slices were then grouped into 5
      regions: proximal epiphysis, proximal part of the metaphysis, diaphysis, distal
      part of the metaphysis, and distal epiphysis. Results validated use of the
      contralateral bone as a control for assessing experimental models or clinical
      cases. Of 858 homotypic slice comparisons between left and right bones,
      significant (P < or = 0.05) differences were detected in 31 (3.6%) of the
      comparisons. Of 168 homotypic region comparisons, significant differences were
      observed in 3 (1.8%) of the comparisons. The greatest variation between left and
      right bones was observed in metaphyseal regions, areas with bony protuberances,
      and regions with prominent bone superimposition. At a power of 0.8 for the
      statistical tests performed in this study, the mean homotypic variation of bones
      in each region is < 5.8% for the proximal epiphysis, 11.3% for the proximal part
      of the metaphysis, 6.8% for the diaphysis, 12.2% for the distal part of the
      metaphysis, and 5.2% for the distal epiphysis.

PMID- 7802388
TI  - Seroepidemiologic survey of Borrelia burgdorferi exposure of dairy cattle in
      Wisconsin.
AB  - An ELISA, using purified flagellin of Borrelia burgdorferi as the solid-phase
      antigen, was used to measure antibody concentrations to B burgdorferi in dairy
      cattle in Wisconsin. Serum obtained from 5,060 cows in 160 randomly selected
      herds in the state were tested. Serum from an additional 2,600 cattle in Barron
      County, Wis, a county with a high annual incidence of B burgdorferi infections in
      human beings, was also tested. Only 7% of the cows that were tested, but 66% of
      the herds that were tested, were seropositive for B burgdorferi. Sixteen percent
      of the herds had a prevalence of > or = 15% seropositive cows, whereas 50% of the
      herds had a prevalence of 1 to 14% seropositive cows. Seropositive herds were
      concentrated in the west-central part of Wisconsin. An association existed
      between the geographic location of seropositive herds and counties in which B
      burgdorferi infection of human beings was acquired (P < 0.05) as well as the
      geographic location of seropositive herds and the geographic distribution of
      Ixodes scapularis (P < 0.05). Barron County, in which B burgdorferi infection is
      endemic, had a significantly (P < 0.05) higher percentage of seropositive cows
      (17%) than did the state of Wisconsin (7%).

PMID- 7802389
TI  - Sheep as maintenance host for Leptospira interrogans serovar hardjo subtype
      hardjobovis.
AB  - Transmission of Leptospira interrogans serovar hardjo subtype hardjobovis from
      naturally infected sheep to uninfected sheep and calves was studied. A
      microscopic agglutination test and ELISA were used to determine specific antibody
      responses in serum. Polymerase chain reaction was used to detect bacterial
      shedding in urine. Six sheep were derived from a dairy farm where cows were
      infected with L hardjobovis. Three of these sheep were seropositive for L
      hardjobovis, and 1 also shed leptospires in the urine. The other 2 sheep shed
      leptospires in the urine 7 days after the first observation date. The 6 sheep
      were placed on an isolated pasture together with a second group of 6 noninfected
      sheep. During the observation period of 140 days, 1 sheep of the second group
      became infected with L hardjobovis. On 5 consecutive days, a urine mixture from
      the 4 infected sheep was sprayed on the heads of 4 noninfected calves. Within 56
      days, all calves that had been sprayed with urine shed L hardjobovis in the urine
      and became seropositive for L hardjobovis.

PMID- 7802390
TI  - Comparison of serum responses in swine after vaccination and challenge exposure
      with Actinobacillus pleuropneumoniae serotype 1.
AB  - Clinical trials have shown that currently available commercial vaccines against
      porcine pleuropneumonia provide inconsistent, serotype-specific protection from
      the disease. Recovery from naturally acquired infection, however, provides solid,
      serotype cross-protective immunity. We examined various serum responses of pigs
      receiving 1 of 4 commercial vaccines or a cell extract, and compared the
      serologic responses of these pigs after challenge exposure with virulent
      Actinobacillus pleuropneumoniae serotype 1. Evaluation of serum included
      complement-mediated killing, opsonizing capacity, IgG titers to whole organisms,
      and cytotoxin neutralization titers. Pigs that received the cell extract had
      fewer clinical signs of pleuropneumonia than pigs in other vaccinated groups, and
      also were significantly (P < 0.05) better protected from development of lung
      lesions and death. Such vaccinates were the only pigs that developed significant
      (P < 0.05) serum antibody titers (ie, protective immune response) to whole-cell
      antigens and to cytotoxin.

PMID- 7802391
TI  - Toxoplasma gondii-specific antibodies in the aqueous humor of cats with
      toxoplasmosis.
AB  - We decided to determine whether Toxoplasma gondii-specific IgM or IgG is produced
      locally or is deposited in the aqueous humor of T gondii-naive cats after primary
      or secondary inoculation with T gondii. Cats were orally inoculated with T gondii
      tissue cysts during weeks 0 and 36. Aqueous humor and serum T gondii-specific IgM
      and IgG were measured, using ELISA, during weeks 0, 2, 4, 6, 8, 12, 16, 20, 26,
      34, 38, 40, 42, 44, 48, 56, 62, 66, and 72 after primary oral inoculation. Total
      immunoglobulin-based Goldmann-Witmer coefficients were calculated to verify
      intraocular antibody production. Toxoplasma gondii-specific IgM was not detected
      in the aqueous humor of any cat. Data indicate that cats have transient local
      production of T gondii-specific IgG in the aqueous humor after primary and
      secondary oral inoculations with T gondii tissue cysts. The intraocular immune
      response to systemic T gondii infection may signal ocular recruitment of antigen
      specific lymphocytes that function independently from the general humoral
      response to T gondii infection. Cautious interpretation of results that suggest
      intraocular production of T gondii-specific IgG in cats with uveitis is
      warranted.

PMID- 7802392
TI  - Comparison of humoral immunity and induction of proliferating T lymphocytes in
      vaccinia virus-infected rabbits and rhesus macaques.
AB  - Vaccina virus (VV) infection induces specific antibodies and cytotoxic T cells in
      various animal species. Therefore, helper T cells also should be induced that
      stimulate the humoral and cellular immune responses. We determined such helper T
      cell activity in 2 species after VV infection. Rabbits and rhesus macaques were
      infected with the Copenhagen strain of VV or with recombinant VV expressing
      retroviral proteins. Animals of both species developed antibodies and specific
      proliferative T-cell response. This reactivity could be enhanced by booster
      infection with VV. The proliferating macaque cells were CD4+ and major
      histocompatibility complex class II-restricted. These data confirm the broad
      immunogenicity of VV. Expression of additional polypeptides expressed from a
      recombinant VV does not lead to altered immune response to VV antigens. However,
      strength of the helper T-cell response, as well as clinical reactions, differed
      between macaques and rabbits. Infection with recombinant VV as delivery vectors
      offers the opportunity for combined vaccination against recombinant proteins and
      does not diminish cellular and humoral immune responses to VV itself.

PMID- 7802393
TI  - Protection against enteric septicemia of catfish (Ictalurus punctatus) by
      immunization with the R-mutant, Escherichia coli (J5).
AB  - The protective effects of immunization with the rough (R) mutant, Escherichia
      coli (J5), were evaluated in an experimental model of Edwardsiella ictaluri
      induced enteric septicemia of catfish (Ictalurus punctatus). Groups of 18 to 25
      fish were administered killed E coli (J5) with or without an aluminum hydroxide
      (alum) adjuvant by intraperitoneal (i.p.) or IM route. Vaccinated fish were
      experimentally infected with virulent Ed ictaluri. Fish were monitored to
      determine survival after Ed ictaluri infection. Fish that received E coli (J5) in
      alum i.p. had enhanced survival (92%), compared with fish given E coli (J5) i.p.
      only (54%, P < 0.05) or fish given saline solution i.p. (56%, P < 0.05). Fish
      given E coli (J5) in alum i.m. had intermediate survival (77%), which did not
      differ significantly (P > 0.05) from survival of fish in the other 3 vaccination
      groups. Serologic responses to Ed ictaluri and E coli (J5) before and after
      immunization with E coli (J5) were determined, using whole-cell ELISA. Serologic
      recognition of both whole cell antigens increased significantly (P < 0.10) in all
      groups; however, the most pronounced increase was observed in fish that received
      E coli (J5) in alum i.p.. These results indicate the i.p. administration of E
      coli (J5) in alum protects against enteric septicemia of catfish.

PMID- 7802394
TI  - Cutaneous delayed hypersensitivity reactions of cattle vaccinated with mutant
      strains of Brucella abortus, using brucellins prepared from various brucellar
      strains.
AB  - Cutaneous reactivity to brucellin was evaluated in 10-month-old heifers
      vaccinated with low-virulence mutant strains of Brucella abortus and was compared
      with brucellin reactions in postparturient cows with active brucellosis. In the
      cows, the cutaneous lesion was characterized microscopically as severe, acute,
      serofibrinous vasculitis; dermal lesions at 6, 12, 25, and 48 hours after
      brucellin injection consisted of endothelial activation and perivascular
      exudation that led to progressive accumulation of fibrin, monocytes, macrophages,
      and lymphocytes. In vaccinated heifers, cutaneous tests were done, using standard
      brucellin, brucellin prepared from strain RB51, and the purified brucellar
      proteins-31K and superoxide dismutase. Negative-control cattle given saline
      solution, did not have cutaneous reactions. Standard brucellin induced the most
      marked reactions in vaccinated heifers. Brucellin from rough strain RB51 caused
      positive reactions in heifers vaccinated with strain 19, but reactions were
      variable in other groups. Skin lesions induced by purified superoxide dismutase
      and 31-kd proteins in vaccinated cattle were not acceptable for diagnosis. Marked
      variability of test responses in vaccinated cattle precludes field use of this
      test to determine vaccination status.

PMID- 7802395
TI  - Enhancement of Pasteurella haemolytica leukotoxic activity by bovine serum
      albumin.
AB  - Growth of Pasteurella haemolytica A1 in RPMI 1640 medium containing 0.5% bovine
      serum albumin (BSA) for 2.5 hours enhanced culture supernatant leukotoxic
      activity (30,700 +/- 12,900 toxic units/ml, compared with leukotoxic activity of
      culture supernatants produced in RPMI 1640 medium alone (120 +/- 40 toxic
      units/ml). Gel filtration chromatography of the leukotoxic activity from RPMI
      1640 medium supernatants in buffer containing 50 mM NaCl indicated a single
      leukotoxic activity peak (peak I) eluting near the gel resin molecular mass
      exclusion limit (estimated molecular mass of approx 8,000 kd). In contrast,
      culture supernatants produced in RPMI 1640 plus bovine serum albumin medium (RPMI
      + BSA) had peak I and 2 additional leukotoxic activity peaks (peaks II and III)
      with estimated molecular mass of approximately 80 and < 30 kd, respectively. All
      leukotoxic activity peaks were composed of approximately 100-kd molecular mass
      leukotoxin protomer, as determined by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis and immunoblotting with a monoclonal antibody against leukotoxin.
      Subjecting culture supernatant leukotoxic activity produced in RPMI + BSA to gel
      filtration chromatography in buffer containing 500 mM NaCl or 6M urea resulted in
      detection of only a single leukotoxic activity peak with estimated approximate
      molecular mass of 250 and 800 kd, respectively. These findings suggest that P
      haemolytica exists as a high molecular mass aggregate with low leukotoxic
      activity which, in the presence of BSA, partially disaggregates to multiple toxin
      forms with enhanced leukotoxic activity. Some of these leukotoxin forms interact
      with dextran-based gel resins at low ionic strength.

PMID- 7802396
TI  - Porcine respiratory coronavirus-mediated interference against influenza virus
      replication in the respiratory tract of feeder pigs.
AB  - Effect of prior porcine respiratory coronavirus (PRCV) infection on replication
      of H1N1-influenza virus in the respiratory tract of swine was studied. In an
      initial experiment, 3 groups of 5 feeder pigs were studied. Pigs of 2 groups were
      inoculated sequentially with PRCV, followed by H1N1-influenza virus at 2- and 3
      day intervals. Pigs of the other group were inoculated with H1N1-influenza virus
      only. Pigs were monitored clinically and examined for nasal excretion of
      influenza virus. In the singly influenza virus-inoculated group, 83% of nasal
      swab specimens were influenza virus-positive over a period of 6 days after
      inoculation. In the dually virus-inoculated groups, only 27% (2-day interval) and
      53% (3-day interval) of nasal swab specimens were virus-positive over the same
      postinoculation period. However, clinical signs of infection in these dually
      inoculated pigs were more severe than those in the singly influenza virus
      inoculated pigs. There were no significant differences in antibody responses
      against influenza virus among the 3 groups of pigs. In a second experiment, 2
      groups of pigs were studied. One group of pigs was inoculated sequentially with
      PRCV, followed by H1N1-influenza virus 2 days later; the other group was
      inoculated with H1N1-influenza virus only. Pigs of both groups were serially
      euthanatized on postinoculation days (PID) 1, 2, 3, and 4 (after influenza
      virus). At necropsy, influenza virus titer and immunofluorescence in lung tissue
      were determined and gross lung lesions were recorded.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7802397
TI  - Effects of aging and dietary protein intake on uninephrectomized geriatric dogs.
AB  - Thirty-one clinically normal Cocker Spaniels, Miniature Schnauzers, and Doberman
      Pinschers (28 female, 3 male) 7 to 8 years old were uninephrectomized (month -2)
      to increase the risk of renal damage associated with reduction of renal mass. Two
      diets, differing principally in protein concentration, were used to test the
      hypothesis that high dietary protein intake causes renal damage in aging dogs.
      For 2 months after uninephrectomy, all dogs were fed diet A (18% protein). After
      glomerular filtration rate (GFR) was measured (month 0), 16 dogs were assigned to
      group A and were fed diet A for an additional 48 months. The other 15 dogs were
      assigned to group B, and were fed diet B (34% protein) for the subsequent 48
      months. At 6-month intervals, GFR and urine protein-to-creatinine ratio (UP/C)
      were determined. At 48 months, terminal studies were done, survivors were
      euthanatized, and tissues were examined. Of 16 dogs in group A, 10 survived,
      compared with 13 of 15 in group B. Among survivors, a significant difference in
      GFR was not found between groups A and B, and decrease in GFR was not evident
      with time in either group. At 48 months, oral administration of casein caused
      minor acute effects on GFR and renal plasma flow in dogs of groups A and B. The
      UP/C values increased significantly (P = 0.001) from baseline values, but the
      increase was not progressive. The UP/C values were not affected by diet. Some
      dogs in both groups developed UP/C > 1.0.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7802398
TI  - Experimental induction of hepatic lipidosis in cats.
AB  - The effect of long-term voluntary fasting on hematologic variables, biochemical
      profiles, and liver histologic findings was assessed in 15 obese cats (> 40%
      overweight). Clinical signs and laboratory results consistent with hepatic
      lipidosis were observed in 12 of 15 cats after 5 to 7 weeks of fasting, and were
      associated with 30 to 35% reduction of initial body weight. Histologic
      examination of successive liver biopsy specimens revealed that obesity was not
      associated with liver parenchymal lipid accumulation, but that fasting resulted
      in lipidosis in all 15 cats. The long-term fast was associated with an early
      (after 2 to 4 weeks of fasting) and significant (P < 0.05) reduction in serum
      urea, glucose, and albumin concentrations, and RBC mass. Fasting for 5 to 7 weeks
      was associated with a significant (P < 0.05) increase in hepatic-associated
      enzyme activities and in total and direct serum bilirubin concentrations.
      Significant (P < 0.05) changes in serum alkaline phosphatase developed as early
      as 3 weeks before the onset of hyperbilirubinemia. Except for development of
      hepatic lipidosis, cats appeared to tolerate the fast without other adverse
      effect. This study confirmed that long-term fasting may induce clinical hepatic
      lipidosis in obese cats. Fasting appears to induce a syndrome of hepatic
      lipidosis that is indistinguishable from feline idiopathic hepatic lipidosis and
      may be an appropriate model to study the pathophysiologic features and treatment
      of hepatic lipidosis.

PMID- 7802399
TI  - Pulmonary histopathologic findings, acid-base status, and absorption of colostral
      immunoglobulins in newborn calves.
AB  - A study was conducted to investigate whether aspiration of amniotic fluid is
      associated with a deleterious effect on absorption of colostral immunoglobulins
      or on blood gas and acid-base values of healthy newborn calves. Fourteen calves
      purchased from commercial sources were transported to a research facility
      immediately after birth and fed colostrum with known concentrations of
      immunoglobulins. Blood samples for gas analyses were collected within 5 hours of
      birth, 24 hours later, and prior to euthanasia. Between 3 and 5 days of age,
      calves were euthanatized by an overdose of barbiturates. Eleven calves had
      evidence of bronchoaspiration of amniotic fluid, as determined by presence of
      meconium, squamous epithelium, or keratin in histologic sections of fixed lung or
      by cytologic analysis of bronchoalveolar lavage fluid. Blood gas tensions and pH
      were within reference ranges in 11 of 14 calves. Aspiration of amniotic fluid
      could not be linked to any specific changes in blood gas tensions, acid-base
      status, or absorption of colostral immunoglobulins. Presence of keratin and
      meconium in the lungs often was accompanied by mild exudative alveolitis and
      focal atelectasis. It was concluded that aspiration of small amounts of amniotic
      fluid with or without meconium is common in calves and is not associated with
      hypoxemia, respiratory acidosis, or failure of passive transfer.

PMID- 7802400
TI  - Pulmonary vascular pressures of strenuously exercising thoroughbreds after
      administration of flunixin meglumine and furosemide.
AB  - High-intensity exercise results in a dramatic increase in mean pulmonary
      capillary blood pressure of horses, and administration of furosemide 4 hours
      before exertion significantly attenuates this exercise-induced increment. To test
      whether this effect of furosemide is mediated via release of prostaglandins,
      right atrial and pulmonary vascular pressures were measured in 8 healthy, sound,
      exercise-trained Thoroughbreds at rest and during incremental-step exercise on a
      treadmill. Horses were studied on 3 separate occasions: after i.v. administration
      of saline (0.9% NaCl) solution, after administration of furosemide (250 mg, i.v.,
      4 hours before exercise) alone, and after administration of flunixin meglumine
      (1.1 mg/kg, i.v., q 8 h for 3 days) and furosemide (250 mg, i.v., 4 hours before
      exercise; last dose of flunixin meglumine was administered 90 seconds after
      furosemide injection). Experiments on each horse were separated by at least 7
      days and were performed in random order. At rest and at the highest workload
      (14.5 m/s on a 5% uphill incline), mean pulmonary capillary blood pressure
      recorded after administration of furosemide alone was not significantly different
      from that recorded after administration of flunixin meglumine and furosemide.
      However, these values were significantly (P < 0.05) less than corresponding
      values of mean pulmonary capillary blood pressure recorded after administration
      of saline solution. Thus, it was concluded that furosemide-induced attenuation of
      the increment in pulmonary capillary blood pressure during strenuous exercise is
      probably not mediated via prostaglandin production.

PMID- 7802401
TI  - Placental transfer of enrofloxacin and ciprofloxacin in rabbits.
AB  - Placental transfer of enrofloxacin and ciprofloxacin was evaluated, using a
      rabbit in situ perfusion model. A two-step infusion program was carried out to
      obtain steady-state maternal plasma concentrations of these drugs. For each
      compound, the placenta in 5 rabbits was perfused for 200 minutes with Earle's
      enriched bicarbonate buffer at flow rate of 1.5 ml/min. To assess reliability of
      the model, most of the determinants of placental transfer (maternal and fetal pH,
      gas balance, heart status, rectal temperature, and protein binding) were
      controlled. In addition, the infusion program included administration of
      antipyrine, a commonly used indicator of placental exchange. Drug concentrations
      were measured in maternal plasma and perfusate by use of a high-performance
      liquid chromatographic assay. Plasma protein-binding estimation indicated no
      differences between the drugs. Placental clearance of the drugs was significantly
      (P < 0.01) different (0.88 +/- 0.13 ml/min for enrofloxacin and 0.06 +/- 0.02
      ml/min for ciprofloxacin). These values accounted for 81 and 5%, respectively, of
      the placental clearance found for antipyrine. These results indicate that caution
      must be taken when enrofloxacin is to be used during pregnancy, and suggest the
      need to extend this type of experiment to species that can be exposed to these
      drugs used for therapeutic or prophylactic purposes.

PMID- 7802402
TI  - Differential artificial ventilation in anesthetized horses positioned in lateral
      recumbency.
AB  - Effects of differential ventilation on gas exchange were studied in 7 isoflurane
      anesthetized, laterally recumbent horses, and were compared with effects of
      conventional ventilation, using similar minute volume. A tracheal tube-in-tube
      intubation technique allowed each lung to be connected separately to an
      anesthetic circle system with a ventilator. Two distribution patterns of tidal
      volume were investigated; half the tidal volume was distributed to each lung and
      two-thirds the tidal volume was distributed to the dependent lung. Effects of the
      combination of these patterns with positive end-expiratory pressure (PEEP) of 10
      and 20 cm of H2O to the dependent lung were investigated. Differential
      ventilation maintained PaCO2, but significantly increased PaO2 from 180 to 270 mm
      of Hg (+44%) and decreased shunt perfusion from 22 to 19% (-15%), regardless of
      the distribution pattern used. Mean airway pressure was lower than the value
      detected during conventional ventilation. The combination of differential
      ventilation with selective PEEP was followed by a decrease in PaCO2 and further
      increase of PaO2 and decrease of shunt, which were similar for both distribution
      patterns. Effects of PEEP of 20 cm of H2O were more pronounced than those of PEEP
      of 10 cm of H2O. Owing to the combined effects of differential ventilation and
      selective PEEP, PaO2 increased to 399 mm of Hg and shunt decreased to 15%. This
      represents increase of 112% and decrease of 33% respectively, compared with
      values for conventional ventilation. Mean airway pressure increased maximally to
      23 cm of H2O, which was 11 cm of H2O greater than the value for conventional
      ventilation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7802403
TI  - In vitro comparison of the effect of parallel and divergent transfixation pins on
      breaking strength of equine third metacarpal bones.
AB  - Breaking strength (torque at failure) of equine third metacarpal bones, with
      transfixation pins placed parallel in the frontal plane and 30 degrees divergent
      from the frontal plane, was determined in vitro. Two transfixation pins were
      placed through the distal metaphysis, using a jig designed to drill the holes in
      the assigned configuration. Paired metacarpal bones II through IV from 12 horses
      were tested in torsion. The torsional moment of the force applied through the
      transfixation pins at failure was compared for each limb. Metacarpal bones with
      divergent pins were significantly (P = 0.030) stronger, compared with those with
      parallel pins. Metacarpal bones with parallel pins failed with longitudinal
      oblique fractures through a proximal bone-pin interface, whereas those with
      divergent pins failed with more comminuted fractures through multiple bone-pin
      interfaces.

PMID- 7802404
TI  - In vitro comparison of the standard short limb cast and three configurations of
      short limb transfixation casts in equine forelimbs.
AB  - Axial stability of equine oblique proximal phalangeal osteotomies with
      application of the standard short limb cast or 1 of 3 configurations of
      transfixation casts was determined in vitro. Transfixation cast methods included
      use of parallel pins, divergent pins, or parallel pins incorporating a metal
      walking bar. Displacement at the osteotomy was recorded for each limb at 4,448 N.
      Standard short limb casts provided significantly (P = 0.0002) less axial
      stability than did any form of transfixation cast. Significant differences were
      not found between the 3 transfixation casts.

PMID- 7802405
TI  - Quantitative assessment of aerial ammonia toxicity to the nasal mucosa by use of
      the nasal lavage method in pigs.
AB  - Effects of atmospheric ammonia (NH3) on the nasal mucosa and somatic growth were
      investigated in pigs exposed to 4 NH3 concentrations (0; 25; 50; and 100 ppm) for
      6 days in a specifically designed air-pollutant exposure chamber. Nasal lavage
      (NAL) was applied to quantify the ammonia-induced inflammatory response by
      measuring the number of neutrophils and the albumin (porcine serum albumin)
      concentration in the NAL liquid. In control pigs, these variables remained
      unchanged throughout the exposure period. In all other groups, an important
      ammonia concentration-related increase was recorded. The equation of the linear
      regression line established between the mean values of the number of neutrophils
      (x 10(3)) per milliliter of NAL liquid (y) recorded at the end of the exposure
      period and the ammonia concentrations (ppm) was: y = 69.7 + 3.3 [NH3] (r = 0.979;
      P < 0.020). The increase in the neutrophil count was significant (P < 0.05) at
      concentrations as low as 25 ppm. For albumin concentration nanograms per
      milliliter, the corresponding equation was: y = 574 + 14.3 [NH3] (r = 0.953; P <
      0.045). However, the first significant change (P < 0.05) in this variable was
      only obtained for the higher concentration (100 ppm). In exposed pigs, a
      concentration-related depression of somatic growth was observed. The equation of
      the regression line plotted relating the individual values of the changes in body
      weight gain recorded over the exposure period expressed as percentage of the
      initial body weight (y) and the ammonia concentration was: y = 3.507-0.203 [NH3]
      + 0.001 [NH3]2 (r = 0.55; P < 0.010).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7802407
TI  - Identification of pharyngeal tonsil in cattle.

PMID- 7802406
TI  - Association between calbindin-D28K and oogenesis in ovaries of chicken embryos in
      vitro.
AB  - The left ovary of chicken embryos was removed and incubated in culture medium
      with a thymidine analogue, bromodeoxyuridine (BrdU), in vitro. In addition,
      fertile chicken eggs were injected with BrdU via the extraembryonic vessels and
      incubated for 24 hours. The ovaries were then processed for immunohistochemical
      localization of calbindin-D28K (a 28-kd vitamin D-dependent calcium-binding
      protein) and BrdU. Calbindin-D28K was detected in the germinal epithelium and in
      cells surrounding the oogonia and oocytes (future granulosa cells) of the
      embryonic chicken ovary. However, BrdU was observed in the nucleus of the oogonia
      and oocytes of the chicken embryonic ovaries. Comparison of the 2 adjacent
      sections, immunostained for calbindin-D28K and BrdU consecutively, indicated that
      BrdU, the marker for cell proliferation was not detected in calbindin-D28K
      containing cells, namely, germinal epithelium and future granulosa cells, in the
      ovary of chicken embryos. These results suggested that calbindin-D28K-containing
      cells in the ovary were not in the process of cell division during the 24-hour
      incubation of chicken embryos.

PMID- 7802408
TI  - Hormonal restructuring of the adult brain: basic and clinical perspectives.
      Preface.

PMID- 7802409
TI  - How do sex and stress hormones affect nerve cells?
AB  - Gonadal and adrenal hormones regulate both structure and neurochemical function
      in neurons that express receptors for them. Gonadal hormone effects mediate
      sexual differentiation of the brain and reproductive tract, and their actions
      during early development program groups of cells in the nervous system to respond
      in male- or female-typical ways to hormones in adulthood. Induction of synapse
      formation is one consequences of brain sexual differentiation, but hormonally
      directed synaptic plasticity is by no means confined to early development and in
      fact occurs cyclically during reproductive cycles in a number of brain regions of
      the female rat, including the hippocampus. The hippocampus responds to adrenal
      steroids as well and undergoes changes in dendritic branching as a result of
      repeated stress. Implications of hormonally directed changes in brain structure
      and neurochemistry are discussed with respect to human pathophysiology.

PMID- 7802410
TI  - Short-term and long-term changes in the postischemic hippocampus.
AB  - We have demonstrated a far more widespread and selective ischemic cell damage
      than previously thought. In area CA3, a distinct subpopulation of interneurons,
      characterized by their spiny dendrites and their calretinin content, was
      selectively vulnerable in the absence of any other CA3 involvement. In the
      dentate hilus, four different types of spiny cells were consistently damaged. The
      common denominator in these two cell groups is the presence of spines on their
      dendrites and hence the greater density of mossy fiber innervation they receive.
      A common mechanism of cell death may be the presence of non-NMDA receptor
      subtypes that are highly permeable to calcium. We speculate that they may
      constitute an important control mechanism in the CA3 region and the hilus, and
      impairment of this mechanism may be causal to delayed neuronal death in CA1. We
      have also shown that neuronal degeneration does not end after delayed cell death
      of CA1 pyramidal cells. Our results suggest that there is progressive
      degeneration throughout the life of the animal and degeneration of additional
      cell populations (e.g. CA1 interneurons and CA3 pyramidal cells) may also occur
      secondary to the insult.

PMID- 7802411
TI  - Androgenic enhancement of motor neuron regeneration.
AB  - In conclusion, the available evidence to date suggests that many of the aspects
      of neuronal functioning affected by gonadal steroids under steady state
      conditions are also significantly affected by steroids under stress conditions
      such as axon disconnection. This argues toward a therapeutic usefulness of
      gonadal steroids in activating and/or accelerating the reparative response of
      neurons to injury, a concept that will be exciting to test in future clinical
      studies.

PMID- 7802412
TI  - Estrogen and nerve growth factor-related systems in brain. Effects on basal
      forebrain cholinergic neurons and implications for learning and memory processes
      and aging.
AB  - Estrogen replacement can significantly affect the expression of ChAT and NGF
      receptors in specific basal forebrain cholinergic neurons. The time-course of the
      effects is consistent with a direct up-regulation of ChAT followed by either
      direct or indirect down-regulation of p75NGFR and trkA NGF receptors, possibly
      due to increased cholinergic activity in the hippocampal formation and cortex and
      a decrease in hippocampal levels of NGF. Current evidence suggests ChAT, p75NGFR,
      trkA, and NGF all play a role in regulating cholinergic function in the
      hippocampal formation and cortex. In addition, all have been implicated in the
      maintenance of normal learning and memory processes as well as in changes in
      cognitive function associated with aging and with neurodegenerative disease. It
      is possible that estrogen may affect cognitive function via effects on NGF
      related systems and basal forebrain cholinergic neurons. Effects of estrogen on
      cognitive function have been reported, as has some preliminary evidence for
      beneficial effects of estrogen in decreasing the prevalence of and reducing some
      cognitive deficits associated with Alzheimer's disease. Whether these effects are
      related to effects on NGF-related systems or basal forebrain cholinergic neurons
      is currently unknown. Indirect evidence suggests that estrogen interacts with NGF
      related systems and that changes in circulating levels of estrogen can contribute
      to age-related changes in hippocampal levels of NGF. These findings have
      important implications for consideration of estrogen replacement therapy in pre-
      and post-menopausal women. Further studies examining effects of different
      regimens of estrogen replacement as well as estrogen combined with progesterone
      on NGF and basal forebrain cholinergic neurons in young and aged animals are
      required. Prospective studies correlating aging and estrogen replacement with
      numbers of basal forebrain cholinergic neurons and hippocampal and cortical
      levels of NGF also need to be performed to better assess the potential benefits
      of estrogen replacement in reducing age- and disease-related cognitive decline.

PMID- 7802413
TI  - Interactions between endocrinology and learning in the avian song system.

PMID- 7802414
TI  - Steroid hormone influences on spatial memory.
AB  - Our studies have shown that both stress-induced, enhanced secretion of
      corticosterone and adrenalectomy-induced, reduced secretion of corticosterone are
      associated with impaired spatial memory performance. On the other hand, estradiol
      administration is associated with enhancements in spatial memory performance.
      Although these changes in performance are small, they are consistent with
      structural changes induced by these hormones (or their lack) on specific cells
      within the hippocampus which form the tri-synaptic loop (a summary of the
      behavioral and morphological effects is shown in Figs. 1 and 2). Thus, these
      results suggest that the morphological changes induced by the hormones have an
      impact on hippocampal function. Important goals of future studies are to seek
      ways to maximize gonadal hormone-dependent enhancements in memory function and to
      minimize adrenal steroid-dependent impairments in memory function as well as to
      understand the mechanisms behind these behavioral and morphological changes.

PMID- 7802415
TI  - Estrogenic effects on memory in women.
AB  - Sufficient evidence now exists to support the contention that estrogen influences
      cognitive functioning in women. Moreover, the data strongly suggest that estrogen
      exerts a specific and not a global effect on cognitive functions. Whereas
      estrogen enhances and/or maintains aspects of verbal memory, it is without
      effect, or possibly even has a negative influence on spatial memory. Indeed,
      there is some preliminary evidence that progesterone may enhance visual-spatial
      skills in women but this needs to be confirmed. Estrogen also exerts a positive
      effect on sexually dimorphic cognitive skills in which females typically excel
      such as verbal articulation and fine motor skills. While the weight of the
      evidence supports the above conclusion, findings across studies are not entirely
      consistent. Some of the methodological problems that weaken these studies include
      generalizing from one or two cognitive tasks to the entire realm of cognitive
      functions, neglecting to assay plasma levels of estradiol to confirm cycle phase
      or compliance with hormone administration and neglecting to consider the
      differential availability to the brain of the various estrogen preparations and
      the effects of different routes of administration. Although, for the most part,
      the menstrual cycle studies and the postmenopausal studies in healthy women show
      that estrogen maintains verbal memory, the effect size is modest. There is no
      reason to believe, for example, that verbal memory is truly impaired in women
      during phases of the menstrual cycle marked by low levels of estrogen. Nor are 45
      year-old untreated, surgically menopausal women clinically impaired to any degree
      that affects their daily functioning in the real world. In both cases, however,
      decrements in performance occur reliably in the laboratory. This raises the
      issue, therefore, of the clinical meaningfulness of these findings. One way to
      address the clinical relevance of the relationship between estrogen and memory
      and thus, on cognitive functioning of the brain, is to examine what is known of
      estrogenic effects on other physiological systems where we already have
      substantial information. For example, the vast majority of women experience bone
      loss following the menopause and many develop osteopenia (bone density more than
      two standard deviations below mean peak bone mass levels) which is asymptomatic.
      Then, with advancing age, some women with osteopenia develop osteoporosis,
      predisposing them to fractures following minimal trauma. It has been estimated
      that 40 per cent of women who live to age 80 will develop spinal fractures and 33
      per cent of women who live to age 90 will experience a hip fracture.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7802416
TI  - Estrogens in the pathogenesis and treatment of Alzheimer's disease in
      postmenopausal women.

PMID- 7802417
TI  - Glucocorticoid therapy of spinal cord injury.

PMID- 7802418
TI  - Gonadal steroids and neuronal plasticity. Studies in the adult rat hypothalamus.
AB  - In this chapter, recent studies on gonadal steroid-induced neural plasticity in
      the adult rat hypothalamus have been described. Neurons in the VMN and DMN are
      capable of rapid, reversible structural alterations in response to a changing
      hormonal environment. Given the importance of the VMN in mediating lordosis in
      female rats, the present studies suggest that hormonally induced morphological
      changes in the VMN may be necessary for the manifestation of lordosis. This
      possibility is supported by the 5,7-DHT studies which indicate that the induction
      of dendritic spines on VMN neurons may somehow decrease the threshold of E needed
      to elicit lordosis. Moreover, the sex differences in hormonal requirements for
      lordosis in 5,7-DHT-treated rats are probably the result of organizational
      effects of gonadal steroids. Our data support the idea that activational effects
      can only be superimposed on existing brain circuitry to a certain degree.
      Finally, the neuronal plasticity seen in the hypothalamus may be an important
      physiological mechanism by which gonadal steroid feedback mediates reproductive
      and behavioral function.

PMID- 7802419
TI  - Regulation of arcuate nucleus synaptology by estrogen.
AB  - Estrogen modulates the synaptology of the hypothalamic arcuate nucleus during
      sexual differentiation of the rat brain in both males and females. In males,
      testosterone of gonadal origin is converted to estrogen in the brain by an
      enzyme, aromatase, which is also present in females. The exposure of the male's
      hypothalamus to relatively high levels of estrogen (following a perinatal
      testosterone surge) leads to the development of a pattern of synaptogenesis which
      does not support an estrogen-induced gonadotrophin surge in the adult. In female
      rats, hypothalamic development occurs with permissively low levels of estrogen,
      enabling a midcycle estrogen-induced gonadotrophin surge and ovulation in
      adulthood. During adult reproductive life in female rats, circulating estrogen
      modulates the synaptology of the arcuate nucleus. The most physiological example
      of this is the 30-50% loss of axosomatic synapses following the preovulatory
      estrogen surge on diestrus-proestrus. Studies on post-synaptic membranes of the
      arcuate nucleus reveal sex differences in membrane organization and protein
      content which are estrogen-dependent. Estrogen apparently stimulates endocytosis
      of areas of post-synaptic membrane that are dense with small intramembranous
      protein particles, resulting in a reduction in the number of small
      intramembranous particles. This also appears to be the physiologic mechanism of
      neuronal changes in females during the estrus cycle. Repeated exposure to
      preovulatory levels of estrogen may lead to an age-related decline in
      reproductive capacity in female rats. Aging females lose the estrogen-induced
      gonadotrophin surge responsible for ovulation. This loss of function may result
      from a cumulative estrogen effect during the repeated ovarian cycles which
      results in a reorganization of the synaptology on which regulates the estrogen
      induced gonadotrophin surge. The membrane organization of the senescent constant
      estrus aged female appears indistinguishable from the males. The hypothalamic
      circuits modulated by estrogen have yet to be delineated. However, recent
      research has shown that GABA, the monoamines, and several neuropeptides are
      participants in the estrogen-sensitive network which regulates GNRH secretion. In
      this regard, present work shows estrogen-induced changes in GABA and dopamine
      synapses in the arcuate nucleus.

PMID- 7802420
TI  - The effects of adrenal steroids and excitatory input on neuronal birth and
      survival.
AB  - The dentate gyrus of the rat forms in three developmental phases, each of which
      is characterized by neuronal birth, migration and death. Recent evidence
      indicates that adrenal steroids regulate neuronal birth, death, and possibly
      migration throughout the life of the animal. However, the observation that very
      few neuroblasts in the developing or adult dentate gyrus express adrenal steroid
      receptors suggests that the effects of adrenal steroid manipulations on
      neurogenesis are indirect. Additional evidence indicates that NMDA receptor
      activation regulates neuronal birth and death in this brain region presenting the
      possibility that adrenal steroids influence these processes through direct
      actions on excitatory afferents. Future studies will address this possibility.

PMID- 7802421
TI  - The sexually dimorphic vasopressin innervation of the brain as a model for
      steroid modulation of neuropeptide transmission.

PMID- 7802422
TI  - Changing Horses.

PMID- 7802423
TI  - [Etiopathogenesis of pituitary tumors].
AB  - In this present work, the authors discuss some recent advances in the
      pathogenesis of pituitary tumours. The model of transgenic mice suggest that
      chronic hormonal stimulation and some growth factors could sustain pituitary
      tumour development. However, these data are not suitable for human pituitary
      adenomas. The evidence that most pituitary adenomas are monoclonal in origin has
      prompted a search for somatic mutations. The mutated Gs alpha are found in only
      30-40% of somatotroph adenomas and the ras mutations seem to be associated with
      the malignant transformation. In some prolactinomas resistant to the
      bromocriptine treatment, quantitative and qualitative alterations of the dopamine
      receptor D2, have been described. Mutations of protein kinase C have been
      identified in some invasive pituitary tumours. Molecular abnormalities have been
      reported in some cases (allele loss at the 11q13 locus, retinoblastoma gene
      mutation, aberrant expression of hst gene, Pit-1 overexpression) but none by
      itself can explain the tumour formation. The pituitary tumorigenesis is certainly
      a multistep process with the intervention of multiple promoting factors.

PMID- 7802424
TI  - [Effects of amiodarone on thyroid hormonal profile. Updating based on new assay
      methods].
AB  - Amiodarone (A) treatment alters the levels of thyroid hormones. We investigated
      whether new hormonal assays are also altered by this drug. Thyroid function was
      determined in 21 patients chronically treated with A and in 30 controls. TSH was
      determined with a third generation assay. Free T3 and Free T4 levels were
      determined by 5 different immunoassays. Equilibrium dialysis (E.D.) was
      considered as the reference assay for FT3 and FT4. With this method FT3 is
      diminished, reverse T3 ans FT4 are increased whereas TSH remained normal. Only
      FT3 determined by an assay using a labelled monoclonal antibody (MAB) appears not
      modified by A. Other methods (chromatography, chemiluminescence and
      radioisotopic) give results in agreement with E.D. Some of these alterations may
      be explained by a marked increase in plasma levels of non esterified fatty acids.
      Hormonal changes induced by A are typically with all but one assays. Whatever the
      method used the determination of TSH remains necessary to avoid misinterpretation
      of the thyroid function tests in A-treated patients.

PMID- 7802425
TI  - [Bilateral gynecomastia revealing malignant feminizing adrenocortical carcinoma].
AB  - We report here a new case of feminizing adrenocortical carcinoma revealed by a
      bilateral gynecomastia in a 50 year old man. The malignant character was already
      suspected on clinical and hormonal data. It was confirmed by the pathology. The
      op'DDD treatment of three weeks was of too short duration to allow any opinion on
      its efficacy.

PMID- 7802426
TI  - [Value and clinical indications of bone mass measurements determined by dual
      photon X-ray absorptiometry. Report of the G.R.I.O. Scientific Committee].

PMID- 7802427
TI  - [Interactions of insulin-like growth factors (IGF) and their binding proteins
      with the plasminogen/plasmin activator system in cultured osteoblasts].
AB  - In biological media, insulin-like growth factors (IGFs) are bound to specific
      high-affinity binding proteins (IGFBPs). Limited proteolysis of these IGFBPs by
      serine proteases facilitates dissociation of the IGFs and their access to
      receptors. Osteoblasts produce IGFs and IGFBPs as well as plasminogen activators
      and inhibitors, and it has been shown that plasmin may be involved in proteolysis
      of the IGFBPs. The IGFBPs secreted by the human osteoblast cell line, MG63, were
      analysed by Western ligand- and immuno-blotting. IGFBP-2, -3 and -4 were found in
      the conditioned media in the absence of stimulatory factors. When the cells were
      incubated with IGF-I, IGFBP-3 and -4 concentrations increased, but IGFBP-2
      production was much less stimulated. When increasing amounts of plasminogen were
      added during the final hours of culture, proteolysis of IGFBP-3 and -4 was
      detected. If the cells had been treated with IGF-I, this was minimal or absent
      and urokinase activity measured in the conditioned media was decreased. This
      study reveals a feed-back mechanism by which IGF-I regulates its own
      bioavailability, acting simultaneously on IGFBP secretion and the proteolytic
      balance.

PMID- 7802429
TI  - [Intragonadal regulation of human follicular genesis: facts and hypotheses].
AB  - In the mammalian ovary, the follicular growth is classically considered to be
      under the control of pituitary gonadotropins. In the human, three cycles (85
      days) are required for a preantral follicle (approximately 0.15 mm in diameter)
      to attain the ovulatory size (approximately 20 mm in diameter). During this
      growing phase, follicular responsiveness to LH and especially to FSH exhibits
      strong changes. Up to diameter of approximately 2mm, follicles are unsensitive to
      cyclic changes in circulating levels of FSH, in terms of quality, growth rate and
      steroidogenesis (basal follicular growth). Follicles larger than 2 mm become
      responsive to FSH, in terms of quality and growth rate, but their ability to
      synthesize estrogen remains very low, they constitute the population of
      recruitable follicles. From its selection, the follicle destined to ovulate
      becomes mores and more responsive, first to FSH and then to LH; all the
      gonadotropin-induced functions are expressed during preovulatory maturation. The
      aim of this review is to clarify the intraovarian regulations involved: (a) in
      the inhibition of gonadotropin-induced functions (basal follicular growth); (b)
      in the acceleration of the growth rate of recruitable follicles and simultaneous
      acquisition of FSH responsiveness of their granulosa cells during the late luteal
      phase, as well as in the "selection" of one of them; (c) in the strong
      proliferation of granulosa cells paralleling with full expression of FSH-induced
      functions (preovulatory maturation before LH surge) and (d) in the inhibition of
      granulosa cell proliferation paralleling with full expression of FSH- and LH
      induced functions (preovulatory maturation after the LH surge). Some peptides and
      proteins, such as growth factors (EGF, IGFs et IGFBPs, TGF-beta), the inhibin
      activin-follistatin system and TNF-alpha, and synthesized by the follicular
      tissues, might be involved in both the inhibition and stimulation of follicular
      responsiveness to gonadotropins. Their possible role during maturation of the
      primate follicle has been analyzed in the light of the most recent findings.

PMID- 7802428
TI  - Transforming growth factor-beta (TGF-beta) and articular chondrocytes.
AB  - Transforming growth factor-beta (TGF-beta) has a dual effect on the proliferation
      of joint chondrocytes. In medium with a low serum concentration, it inhibits cell
      growth, while in medium supplemented with 10% fetal calf serum it stimulates cell
      growth. This stimulation leads to a higher replication rate an a larger number of
      cells in the G2/M phase of the cell cycle. Since these cells have already
      replicated their DNA, they can begin mitosis when stimulated by a EGF type
      factor. This mechanism involves the systems of the TGF-beta receptors which
      appear to vary with the cell cycle. In addition, a glycane inositophosphate may
      play a role as a second messenger for TGG-beta in this action. Finally, TGF-beta
      cannot restore the chondrocyte phenotype in dedifferentiated cells nor limit the
      dedifferentiation process. It exerts a opposing effect to the deleterious effects
      of interleukin-1 by inhibiting the expression of the receptors of this cytokine
      at the level of transcription. These in vitro effects would suggest that TGF-beta
      plays an important role in the repair potentiality of joint cartilage especially
      in arthrosis. In vivo studies are however necessary to verify this hypothesis.

PMID- 7802431
TI  - The use of recombinant FSH for ovulation induction.
AB  - Recombinant human FSH (recFSH) was tested in a phase II study in 50 couples
      superovulated for IVF. Rec FSH alone was used in 10 women (Group 1). Intranasal
      buserelin spray (150 micrograms x 4 daily) was used in a flare-up protocol (10
      women; Group 2) or in a desensitization protocol (10 women; Group 3) in
      combination with rec FSH. Desensitization using Triptorelin depot (3.75 mgIM)
      followed by rec FSH was given to 10 women (Group 4), while the same agonist was
      used subcutaneously (200 micrograms/daily) in Group 5 (10 women). In the five
      groups rec FSH induced multiple follicular growth. Significantly more ampoules
      rec FSH were required when a GnRH agonist was used. I all groups 9 to 11 mature
      oocytes were retrieved per cycle. In 6 couples there was an absence of
      fertilization due to severe sperm anomalies (5 couples); one couple suffered from
      idiopathic infertility. Fertilization and cleavage was normal in 44 couples.
      Forty-three transfers of 2.3 to 2.8 embryos yielded 10 pregnancies. Nine healthy
      babies were born. Superovulation for IVF was successful and safe by using rec FSH
      alone or in combination with various GnRHa dosages and protocols.

PMID- 7802430
TI  - [LH receptors. A new family of G-protein receptors].
AB  - Monoclonal antibodies have been raised against porcine LH receptor and allowed to
      clone the corresponding messenger RNA from testicular cells. The structure of the
      LH receptor have been determined. It shows similarities but also differences to
      other G protein coupled receptors. In particular a large extracellular domain is
      specific for that family of receptors. Variants forms of the LH receptor
      generated by alternative splicing and lacking transmembrane domains have been
      isolated. Immunochemical and immunocytochemical studies have been performed.
      Three different forms of the LH receptor are physiologically expressed: a mature
      85 kDa transmembrane species, a 68 kDa high mannose containing species
      corresponding to a precursor which accumulate inside the cells, and truncated 45
      48 kDa molecular weight species corresponding to the variant messenger RNAs
      identified during the cloning of the receptor. A novel zonation of the ovary has
      been described by immunocytochemical studies. Cross hybridisation with the LH
      receptor clone allowed to isolate the related human TSH receptor from thyroids.
      The human LH and FSH receptor genes have been localized to chromosome 2p21 and
      the TSH receptor gene to chromosome 14q31. The genes are very large and have
      introns only within their 5' part corresponding to the extracellular domain of
      the receptor.

PMID- 7802432
TI  - [Growth factors and bone tissue. Implications in the formation of bone matrix].
AB  - Bone formation is highly dependent on the number of osteoblastic cells.
      Simulating factors which recruit osteoblastic cells play an essential role in
      regulating bone formation. Several growth factors produced locally by bone marrow
      cells and osteoblasts regulate cell growth and differentiation of osteoblastic
      cells. These growth factors may be systemic or local and can be stocked in the
      matrix. The factors secreted locally play a dominant role in regulation and are
      stocked in an active form in the bone matrix. Growth factors act through both
      autocrine and paracrine effects, or as local mediators of hormones and
      compression forces. The wide range of effects of the local growth factors and
      cytokines on bone cells, and the numerous interactions between these factors lead
      to precise regulation of the osteoblastic function. Thus these factors plan an
      extremely important role in local regulation and cell growth and osteoblastic
      differentiation, and are highly implicated in local control of bone formation.

PMID- 7802433
TI  - [Role of growth factors and cytokines in osteoclastic differentiation and bone
      resorption].

PMID- 7802434
TI  - [Autocrine regulation of cell proliferation and secretion of insulin-like growth
      factor I (IGF-I) in osteoblastic cell line MC3T3-E1].
AB  - Bone cells maintained in culture produce different growth factors which modulate
      cell growth via a mechanism of auto/paracrine regulation. IGF-1 is abundantly
      produced by murine bone cells where it acts as a mitogenic agent. The aim of this
      work was to study the effect of IGF-II, TGF beta 1, basic FGF (FGFb) and PDGF on
      cell growth and production of IGF-1 in the murine osteoblastic clonal cell line
      MC3T3-E1. IGF-1 was assayed by RIA after elimination of the IGF binding proteins.
      After 24th of treatment in culture conditions without serum, incorporation of
      [3H] methylthymidine increased significantly in MC3T3-E1 treated with IGF-II,
      FGFb and PDGF. The effect was dose-dependent. At low cell density (2.5 X 10(4)
      cemm/cm2) and after 24 h treatment, IGF-II at 10 ng/ml led to a 220% increase in
      IGF-I production in MC3T3-E1 cells (9.5 +/- 1.5 vs 4.2 +/- 0.44 ng/micrograms
      protein, p < 0.001) while TGF beta 1, FGFb and PDGF at 1 ng/ml led to a
      significant decrease (65, 95 and 85% respectively) in IGF-I (TGF beta 1: 1.5 +/-
      0.3 ng/micrograms; FGBb: 0.21 +/- 0.04 ng/micrograms; PDGF: 0.66 +/- 0.1
      ng/micrograms; p < 0.001). Production of IGF-I was controlled by a dose-dependent
      relationship and varied as a function of incubation time and cell density. IGF-II
      led to an increase in mRNA coding for IGF-1 as early as the first hour after IGF
      II addition with a maximal effect at 6 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7802435
TI  - [Fibrous inflammatory polyp of the digestive tract. Apropos of 5 cases].
AB  - Inflammatory fibroid polyp is a rare benign tumor of the digestive tract. The
      authors report three cases: two intestinal and one gastric. These cases are of
      particular interest because of the association ill one case of an intestinal
      submucosal lipoma with the inflammatory fibroid polyp, and the existence in the
      gastric case of an inflammatory reaction caused by food debris. This offers,
      further evidence in support of the theory implicating a chronic inflammatory
      reaction.

PMID- 7802436
TI  - [Leiomyosarcoma of the small intestine. Review of the literature apropos of 3
      cases].
AB  - This study reports three cases of leiomyosarcoma of the small intestine (a rare
      malignant neoplasm) presenting in our department of general surgery over a period
      of ten years. Tumors in these three patients were located in the jejunum and
      clinical features included severe gastrointestinal bleeding, intestinal
      obstruction and/or abdominal pain. All three patients underwent radical surgery.
      None received radiotherapy and chemotherapy in addition. One is alive and in
      complete remission for four years while the other two died, after two and twenty
      two months respectively. There follows a discussion, based upon the literature,
      of epidemiological, histopathological, clinical, diagnostic and treatment
      aspects. Particular stress is placed upon the difficulty of establishing the
      diagnosis before surgery, since symptoms are often absent or non-specific and
      vague until the malignant small bowel tumor has progressed to the point of
      causing a complication. Surgery continues to play a primary role in the treatment
      of leiomyosarcoma. Further studies are required to identify prognostic factors
      and to assess the efficacy of radiotherapy and chemotherapy in this type of
      malignant neoplasia.

PMID- 7802437
TI  - [Hepatic candidiasis caused by Candida glabrata].
AB  - The incidence of disseminated candidiasis is increasing. Liver involvement is
      frequent but rarely diagnosed. The authors report a case of disseminated
      candidiasis due to Candida glabrata with liver metastases. The presence of
      hepatic lesions was diagnosed by CT scan and parasitological examination of liver
      abscess contents obtained by CT-scan-directed puncture-aspiration. The outcome
      was favorable with amphotericin-B (cumulative dose of 1 g) and flucytosin.
      Aspects of hepatic involvement in disseminated candidiasis is discussed, together
      with the role of Candida glabrata in pathology of this type.

PMID- 7802439
TI  - [Cystic lymphangioma of the spleen. An exceptional site].
AB  - The authors report a case of cystic lymphangiomatosis of the spleen. Study of
      this case and a review of the literature confirm the rarity of this site and
      problems of differential diagnosis with hydatid disease. Treatment remains
      surgical and the prognosis is good.

PMID- 7802438
TI  - [Tuberculous abscess of the liver. Apropos of 2 cases].
AB  - The authors report two cases of tuberculous liver abscess. They stress the rarity
      of this site, and differential diagnostic difficulties with other types of
      infection and liver tumors, notably amebiasis, hydatid cyst and carcinoma. Echo-
      or Scan-guided needle biopsy is useful for diagnosis and, in some cases,
      treatment by drainage of the purulent cavity.

PMID- 7802440
TI  - [Zollinger-Ellison syndrome: diagnostic and therapeutic strategy].

PMID- 7802441
TI  - [Current status of immunization in the Armed Forces: need of continuous
      adaptation of vaccinations against cerebrospinal meningitis, typhoid and
      hepatitis A].
AB  - The history of military medicine has always been closely linked with that of
      vaccinations. Doctors of Armed Forces, doctors of collectivities, have
      contributed to vaccination progresses in large amounts. But evolutions are often
      rapid here: epidemiological modifications, improvements in the existing vaccines
      or creation of new vaccines, diversification of military specificities. Three
      recent modifications in the vaccination schedule of the Armed Forces show this
      necessary adaptation: systematization of the meningococcal A+C vaccination during
      the incorporation, because of the modification of the disease's epidemiological
      profile; increase of the frequency in serogroup C with a mortality increase (9
      cases of death out of 10 observed between 1991 and 1992); cancellation of
      antityphoid vaccination for recruits serving in home country. Indeed the disease
      has become rare in France, and this is often due to imported cases (3 cases in
      the Armed Forces in 1992); introduction in 1994 of vaccination against viral
      hepatitis A, systematic under the age of 25 years and after a serological
      selection above for servicemen having to serve overseas or for outside
      operations. These 3 examples show the necessity to have updated and adaptable
      vaccination schedules.

PMID- 7802442
TI  - [Home care and health insurance].

PMID- 7802443
TI  - [The outlook for liaison between medical examination and home therapy].

PMID- 7802444
TI  - [Outpatient chemotherapy with continuous infusion of 5-fluorouracil (CI 5-FU) and
      intravenous bolus leucovorin (IVB LV) in advanced gastrointestinal cancer].
AB  - This study was designed to evaluate the efficacy, toxicity, and quality of life
      (QOL) of outpatient chemotherapy with 5-FU and LV in advanced gastrointestinal
      cancer. Treatment consisted of CI 5-FU 450-500 mg/body/day, days 1-28, IVB LV 30
      mg/body q wk. 5-FU was administered with the Baxter infusor (0.5 ml/hr). LV was
      not administered if Grade 2 mucositis occurred. Seven patients (pts) with
      advanced gastrointestinal cancer (esophageal -2, gastric -1, colorectal -4) have
      been treated to maintain the efficacy of prior inpatient chemotherapy, and two
      pts with colorectal cancer instead of oral UFT. And to evaluate toxicity and QOL,
      six pts (bile duct -1, gastric -2, colorectal -3) treated as adjuvant
      chemotherapy were added. The median duration of response of the nine pts was 3.03
      months. Because of mucositis, the administration of LV was restricted. The mean
      administration of it was 2.1 times (62 mg). Grade 3 or 4 toxicities of mucositis
      were seen in 40% of the cases. Grade 1 or 2 skin toxicities were seen in all pts.
      Mean score of QOL in these outpatients chemotherapy was 78.0 +/- 11.5, ranked
      between inpatient chemotherapy (5-FU+CDDP 59.0 +/- 13.8) and oral UFT (91.8 +/-
      6.1). In conclusion, this schedule of 5-FU and LV combination offers a high
      patient QOL and is suitable for advanced gastrointestinal cancer treatment.

PMID- 7802445
TI  - [Usefulness of 5-FU high-dose continuous therapy at home in patients with
      recurrent gastric and colon cancer].
AB  - Recurrence of gastric cancer or colon cancer was observed in some patients who
      received 5-fluorouracil (5-FU) high-dose continuous Methotrexate (MTX)-Leucovorin
      (LV) therapy (FML therapy) previously. 5-FU high-dose 48-hours continuous therapy
      (5-FU therapy) as maintenance therapy for the patients was performed in the
      hospital and successively at home. The patients included 3 with recurrent gastric
      cancer and 2 with recurrent colon cancer: there were 4 males and 1 female, the
      mean age was 51.8 years (33-59 years). All patients had received FML therapy
      during the hospital stay before the maintenance chemotherapy at home. 5-FU
      therapy (30 mg/kg/day x 2 days/w), 30.2 courses on an average (11-40 courses),
      was performed through a catheter (Port-A-Cath), which was introduced into the
      right subclavian vein and placed under the skin, with a Baxter infusion pump. The
      concentration of 5-FU was 197 +/- 172-401 +/- 127 ng/ml between the 2nd and 48th
      hour. Adverse reaction included anorexia in 5 patients, stomatitis in 4,
      pigmentation in 4, leukopenia in 3, neuropathy in 2 and alopecia in 1. The
      therapy was effective for 10.4 months on an average (4-18 months) and the mean
      survival period was 12.0 months (7-18 months).

PMID- 7802446
TI  - [Home infusion chemotherapy in patients with relapsed or recurred stomach and
      colorectal cancer].
AB  - Five patients with distant metastasis from colorectal cancer who had good
      nutrition were treated with continuous intravenous administration of 5-FU
      infusion (400-450 mg/body/day) by infusor. The other five patients with advanced
      stomach cancer who could not have so good nutrition were receiving home parental
      nutrition (HPN, 1,200 kcal/day) and continuous or intermittent 5-FU infusion (250
      500 mg/body/day) using Lentinan at the same time. In colorectal cancer, one
      partial response (PR) and one complete response (CR) were obtained. And in
      stomach cancer, only one NC were obtained but we could perform these HPN and
      chemotherapy for 13 months at home. According to our trial, we thought these
      chemotherapy and nutrition at home were useful to improve the quality of life of
      patients with GI tract cancer.

PMID- 7802447
TI  - [Clinical study of ambulatory cancer chemotherapy for recurrent breast cancer].
AB  - To evaluate ambulatory cancer chemotherapy, the clinical response, toxicities and
      survival time were analysed among 12 outpatients with recurrent breast cancer who
      were treated by sequential methotrexate (MTX)/5-FU therapy for the past 2 years.
      In this study, MTX (70 mg/m2, i.v.) and 5-FU (370 mg/m2, d.i.v.) were given on
      days 1 and 15 every 4 weeks, the 5-FU being given one hour after the MTX. Partial
      response (PR) was observed in 3 patients (25%), no change (NC) in 9. One-year
      survival ratio was 59%, and 7 out of 12 patients survived at the end of this
      study. The median disease free interval was 7.3 months, and 3 cases survived for
      more than one year without disease. Although nausea/vomiting, stomatitis,
      leukopenia and alopecia were noted, no severe side effects were observed. These
      results suggested that sequential MTX/5-FU therapy might be a useful ambulatory
      cancer chemotherapy for patients with recurrent breast cancer.

PMID- 7802448
TI  - [Low-dose continuous infusion therapy 5-FU and CDDP enabled terminal patients
      with lung and rectal cancer to remain at home].
AB  - CDDP and 5-FU are time dependent drugs and their increasing effect is expected
      because of the dual chemical modulation. The low dose continuous infusion of CDDP
      and 5-FU was applied to the terminal adenocarcinoma patients with the metastatic
      lesions. One patient was 42 years old lung cancer patient with the metastatic
      lesions in the liver, the bone, the pericardial space, the underskin, the muscles
      and the lymph nodes (stage IV). The another patient was 61 years old rectum
      cancer patient with lung and hepatic metastasis (stage V). Both patients were
      directly informed of the true name of the disease and the poor curability from
      the physician in charge. The physician promised them to take the home therapy as
      much as possible in order to pursuit their own life value at home. The lung
      cancer patient got the radiotherapy first to remove the bone pain and the rectum
      cancer patient was operated to make the stoma to avoid the obstructive ileus
      beforehand. After the therapy, two patients took the low dose continuous infusion
      of CDDP and 5-FU. In both cases, the abdominal symptoms such as nausea and
      vomiting due to the therapy were not recognized and the hematopoietic disorders
      and the renal failure were slight, so they could get the therapy continuously for
      very long. The lung cancer patient lived 9 months after the diagnosis and the low
      dose infusion chemotherapy has continued for 7 months, the home stay for 4
      months. The rectum cancer patient lived 13 months and the same chemotherapy has
      continued for 12.5 months, the home stay for 7.5 months. The low dose continuous
      infusion therapy of CDDP and 5-FU is an effective treatment for terminal cancer
      patients as one of the home therapies from the point of the QOL (quality of
      life).

PMID- 7802449
TI  - [Effect of prophylactic intra-arterial infusion of anticancer drugs on post
      hepatic resection for hepatic metastasis of colorectal cancer].
AB  - Prophylactic intra-arterial infusion of anticancer drug on post hepatic resection
      for hepatic metastasis of colorectal carcinoma were performed 8 cases. In our
      cases consisted of 8 patients of mean age of 54.3 years (male 3 cases and female
      5 cases, synchronous metastasis 4 cases and metachronous 4 cases). All patients
      were received intra-arterial bolus injection of MMC (4-8 mg/body) at day 1 and
      continuous infusion of 5-FU (250-750 mg/body) for 7 days on admission. After
      discharged, patients were received bolus injection of 5-FU (250-750 mg/body) for
      once a week. Side effect of this treatment was not appeared and all of them
      obtained very good QOL. There were no recurrence sign of residual liver and this
      procedure was very useful method for post hepatic resection for hepatic
      metastasis of colorectal cancer.

PMID- 7802450
TI  - [Optimal induction and maintenance of the hypertensive state an important factor
      in clinical advantages of angiotensin II induced hypertension chemotherapy
      (IHC)].
AB  - Angiotensin II induced hypertension chemotherapy (IHC) is a drug delivery system
      in which the functional difference of microcirculation between tumor and normal
      tissue was applied. IHC records of the patients with advanced gastrointestinal
      cancer, admitted in our hospitals were analysed according to the patterns of the
      maintenance level and range of blood pressure. Those who were possible to get
      ambulatory life had significantly good response and long survival in addition to
      better performance status before IHC, comparing with those who had continued
      admission life. An optimal range of elevation level and stable maintenance of
      hypertension induced by the infusion of angiotensin II was essentially required
      to obtain a good response.

PMID- 7802451
TI  - [Home chemotherapy for peritoneal carcinomatosis].
AB  - Nineteen patients diagnosed with peritoneal carcinomatosis were treated by in
      home chemotherapy over a period of four years from August, 1990 to July, 1994.
      Primary diagnoses of the four male and 15 female patients included 12 cases
      gastric cancer (four males, eight females), five cases of ovarian cancer, one
      case (female) of appendicular cancer, and one case (female) of breast cancer. In
      addition to oral administration of UFT-E and 5'-DFUR, chemotherapy included
      weekly intravenous injection of a massive dose of 5-FU (1,000 mg/m2),
      subselective intraaortic infusion and intraperitoneal infusion using a reservoir.
      These methods were used individually and in combination. The drugs used included
      5-FU, CBDCA, CPA, THP, and EPIR. Subselective intraaortic infusion was performed
      by low dose continuous infusion using the Baxter infusor multiday type. Six
      gastric cancer patients lived normally for over one year, while four died in less
      than a year. All ovarian and appendicular cancer patients were CR, the breast
      cancer patient was PR. Ten patients continued working at their jobs while
      receiving at home chemotherapy treatments. Diuretics were used to alleviats
      ascites. Although there were no side effects on digestive organs, 5-FU and CBDCA
      were mixed with 100 mg hydrocortisone in the infusor to improve cachexia, and
      promote appetite and activity. Bone marrow suppression was very slight at these
      dosages, and weekly checkups were adequate. The at-home rate (number of days at
      home/entire period since onset) of all patients was 78%.

PMID- 7802453
TI  - [Support system for long-term morphine administration to terminal cancer patients
      at home--verification from three patients at home with terminal cancer].
AB  - The nursing department at the Saitama Prefectural Cancer Center established a
      Nursing Consultation Section in April 1993 and a Visiting Nursing Program in May
      1993 with the purpose of supporting cancer patients who desired home care. From
      these dates through March 1994, 1,021 patients were instructed in home care
      methods and visiting nursing was provided in 98 cases. Of these, three patients
      with terminal cancer received long-term ameliorative treatment using orally
      administered morphine and were able to maintain satisfactory QOL through their
      terminal periods. The results are reported herein.

PMID- 7802452
TI  - [Trial of self-management of outpatients with implanted reservoir for arterial
      infusion of anticancer drugs].
AB  - We attempted to instruct the outpatients with malignant liver tumor (metastatic
      liver cancer and advanced hepatocellular carcinoma) who received intermittent
      arterial infusion chemotherapy using implanted reservoir to detach the devices
      for arterial infusion by themselves at home. All patients who received our
      instruction could master self-detachment at home, which shortened the
      hospitalized day. And patients' desire for this treatment promoted with
      improvement of the recognition of their families to participate in treatment
      together. We experienced no trouble which disturb the treatment. This methods was
      considered to promote the improvement of QOL of these patients.

PMID- 7802454
TI  - [Long-term pain control in terminal care with home hospice care].
AB  - Ideal pain control in terminal care at home is the usage of oral or rectal
      administration of analgesics. If these methods of administration cannot manage
      pain sufficiently, muscular or intravenous injection of analgesics will be
      necessary. This is the report of a 66-years-old female who had bone metastasis of
      uterine cervical carcinoma and gait disorder, and had received chemotherapy along
      with radiotherapy. At her third admission to our hospital, the total radiation
      done nearly reached the maximum level. We, therefore, administered morphine
      sulfate (MS contin) for pain control but it induced strong side effects. Therapy
      was then changed to continuous infusion of morphine hydrochloride using a Baxter
      infusor. As a result, pain relief was achieved without inducing side effects, and
      the patient was able to return to care at home. At that time, the patient's
      remaining life was expected to return to be about 6 months. However, in fact, she
      was able to survive for 823 days since then, and 637 days (77.4%) of that time
      was spent at home. This is considered as terminal care performed mainly at home,
      with subsidiary care at the hospital. The most important factor which contributed
      to the success of this care was the pain control by an epidural block infusor. In
      order to realize worth-while care for patients, it is important to offer various
      treatment programs which can satisfy the needs of patients and their family, and
      pain control will be one of the most important factors for cancer patients who
      wish to spend their limited time with their family.

PMID- 7802455
TI  - [An approach to home therapy for cancer pain patients].
AB  - Recently, in consideration of cost performance and improvement in quality of life
      (QOL) of the patient, the significance of home care and outpatient treatment has
      also been recognized in Japan. A terminal cancer patient who had local recurrence
      in the pelvic region after surgery for rectum carcinoma, was treated for cancer
      pain by us with a continuous epidural infusion of morphine by means of a
      prolonged operating continuous infusion device. The treatment made home therapy
      possible and allowed the patient to return to normal social activities. Based on
      this case, the significance of and issues regarding home therapy are discussed in
      this study.

PMID- 7802456
TI  - [Home terminal care for terminal gastric cancer patients--case of epidural
      morphine injection].
AB  - Pain management at home for a terminal gastric cancer patient unable to take
      medications orally was made possible by a combination of serial morphine drip
      infusion and epidural anesthesia with morphine on a continuing basis using a
      disposal syringe. Before the patient was discharged, a conference was held to
      prepare for home care. Besides the patient and family, it was attended by the
      primary care doctor, ward nurse, home nurse, pharmacy staff, pain clinic doctor
      and hospital office personnel. The patient was duly informed of the disease by
      name and, thanks to fine cooperation from the medical staff, had achieved a good
      understanding, and spent his remaining time meaningfully. Morphine dosages upon
      discharge were 80 mg/day by drip infusion and 90 mg/day epidurally. For times of
      increased pain, the patient was instructed in how to self-administer 0.5%
      Mepivacaine (5 ml/time) with a syringe using an epidural catheter equipped with a
      3-way stopcock. When this proved insufficient to control the pain, the patient
      was instructed to come for outpatient treatment on an emergency basis. With one
      visit per week to the hospital and home visits by a nurse once or twice a week,
      the patient managed at home for 82 days before increased pain resulted in
      rehospitalization. After the pain was brought under control and the patient was
      discharged, he was again hospitalized 5 days later. The pain control up until the
      time of death was by drip infusion of up to 1,200 mg/day morphine.

PMID- 7802457
TI  - [Bathing a patient with cancer pain treated with continuous epidural blockade-
      subcutaneous catheter track and Lapack method].
AB  - Continuous epidural blockade is considered to be the most useful device for the
      management of cancer pain. However, it has the disadvantage to compel the
      patients to restrict their daily activities. We report a unique "Subcutaneous
      catheter track & Lapack-method" that enabled a patient with epidural catheter to
      safely bath at home. A 56-year-old male with a local recurrence of rectal cancer
      was suffering from perineal pain, which was well controlled by oral and epidural
      morphine. Since his wishing was to bath, we made a long subcutaneous catheter
      track with Tuohy-needle to prevent infection, and let him bath with transparent
      film dressings (Bioclusive) and Lapack to tightly cover and seal up the catheter.
      Although subcutaneous pustule occurred 7 days after the beginning of bathing, it
      was easily cured by local disinfection. He was able to enjoy bathing without any
      infection with this method at home for about 2 months after discharge, until he
      returned to the hospital. "Subcutaneous catheter track & Lapack-method" offers a
      safe and comfortable bathing to patients with epidural catheter, and contributes
      to the improvement of their quality of life.

PMID- 7802458
TI  - [Eligibility from clinical science for domiciliary cancer treatment].
AB  - To establish domiciliary treatment for cancer patients, following conditions must
      be settled. They are eligibility from clinical science, intentions of patients
      and their family, social and economical aspects, compatibility with medical
      service laws in Japan, and so on. Eligibility from clinical science should be the
      first matter to be settled among them. From the view of clinical science, medical
      care practices must be carried on in a correct manner even in patients' homes. In
      this study we focused on suitability from clinical science and examined
      possibility of domiciliary treatment for 111 inpatients in our hospital on April
      6 th 1994. When the possibility was respectively judged by two nurses in our
      domiciliary cancer treatment committee, a difference appeared in the numbers of
      the candidates for domiciliary treatment. Finally the committee decided that 37
      inpatients could receive medical care practices in their homes. The analysis of
      the reason in difference by two nurses made us recognize that the process of the
      selection of cancer treatment must be properly constructed for the well-qualified
      domiciliary treatment.

PMID- 7802459
TI  - [Prolonging home residence and treatment of cancer in patients with recurrent
      stomach cancer].
AB  - A study was conducted on 27 patients with cancer of the stomach who died from a
      postoperative recurrence of the cancer, 26 of whom died in the hospital and one
      of whom died at home. The period from the manifestation of initial symptoms of
      the recurrence to confirmed diagnosis was less than two months in 20 of the 26
      cases (77%). The period from confirmed diagnosis to terminal hospitalization was
      in excess of three months in 11 of the 26 cases (42%). Of these cases, there were
      some in which it appeared that the time spent at home could have been extended
      through means such as another operation, insertion of an intraperitoneal access
      apparatus, or insertion of a subselective movable catheter. Forty-six percent
      (46%) of the patients were notified of their diagnosis, but none of them were
      notified of the recurrence of the cancer, suggesting the difficulty of notifying
      a patient of a diagnosis of cancer recurrence. A private home-care medical system
      was used in the case of the patient who had died at home of terminal stomach
      cancer. There were no major problems with this system other than the complaint
      that it placed a great financial burden on the family.

PMID- 7802460
TI  - [Briefly summarized nursing card for patients with advanced cancer receiving out
      hospital management].
AB  - Briefly summarized nursing card to perform adequate nursing for readmission
      patients with advanced cancer receiving outhospital management was developed and
      its clinical usefulness for nursing is discussed. The card is 18 cm x 13 cm,
      differential colored for diseases, and written only necessary summarized
      informations for adequate nursing at the patient's emergent readmission. By using
      this card for 24 patients, it was very useful because of its very selected, brief
      and summarized information. This card has much usefulness for nursing of such
      patients.

PMID- 7802461
TI  - [Home therapy approach in cancer patients-nutrition therapy (case 1-1)--a case of
      recurrent gastric cancer with home parenteral nutrition].
AB  - This paper describes a case of recurrent gastric cancer with home parenteral
      nutrition (HPN). A 48-year-old man underwent nutrition support with HPN for the
      last 6 months. We treated the patient with adjuvant chemotherapy and provided
      pain management along with HPN treatment. The patient was able to achieve a
      meaningful and satisfactory quality of life. We concluded that HPN for recurrent
      cancer patients is a relatively safe and effective means of improving and
      maintaining the nutritional status. We think the following is important in order
      to establish home infusion therapy. 1) Organization of a home care team
      (physician, nurse, pharmacist, dietitian, and caseworker) and a practice-team
      approach. 2) Establishment of a home infusion system in home care. 3) Preparation
      of patient manuals by the medical staff. 4) Establishment of sterility
      preparation and delivery system in home infusion therapy. 5) Establishment of a
      patient-information-communication system by connection with other hospitals,
      clinics, and home care companies.

PMID- 7802463
TI  - [Home therapy approach in cancer patients-chemotherapy (case 2-1)].

PMID- 7802462
TI  - [Home therapy approach in cancer patients-nutrition therapy (case 1-3)].
AB  - When nutrition therapy is necessary in a long time in care of cancer patient, we
      take Home parenteral nutrition (HPN) as one selection rami. We enforced it than
      1987, but the home care center was established in 1993 to carry out it more
      smoothly. Now the center becomes the leading role, and pattern of home therapy
      which was suited for a patient of each in cooperation with each part in hospital
      place and support group of external is made, and it is enforced. Staff of the
      center consists of it than doctor, nurse, dietitian, apothecary, medical social
      worker care office workers. When HPN of each patient is enforced, the staff of
      field of specialty will each solve the problems that there is. When all is not
      possible in the center, a private being at home care support company, affiliated
      hospital is connected with. We detain catheter during admission to thing of
      approximately 1 week, and education necessary for HPN is enforced to a patient
      and family. An exclusive manual is used for education.

PMID- 7802464
TI  - [Home therapy approach in cancer patients-chemotherapy (case 2-2)].
AB  - We have performed intra-arterial biochemical modulation chemotherapy of 5-FU with
      Leucovorin for patients with unresectable liver metastases from colorectal
      cancer. Three regimens were performed. A; weekly bolus injection of 5-FU and
      Leucovorin (6 cases), B; 7 days continuous injection of 5-FU after bolus
      injection of Leucovorin (4 cases), C; 5 days simultaneously continuous injection
      of 5-FU with Leucovorin (6 cases). The results were; response rate was A:0%,
      B:25%, C:33% and survival rate for patients of C method was better than that for
      patients of A and B method. Four patients complained mild nausea of less than
      Grade 2, but only one patient of C method. These results suggest that
      simultaneously continuous intra-arterial injection of 5-FU with Leucovorin is an
      excellent therapy for patients with unresectable liver metastases from colorectal
      cancer.

PMID- 7802466
TI  - [Home therapy approach in cancer patients--pain control (case 3-2)].

PMID- 7802465
TI  - [Home therapy approach in cancer patients-chemotherapy (case 2-3)--intra-arterial
      infusion cancer chemotherapy for hepatic metastasis of colorectal cancer--case
      report].
AB  - The development of interventional radiology and the like has made it possible to
      reduce the invasion and expand the applicability of intra-arterial infusion
      chemotherapy for unresectable cancer. By employing such methods and combining
      chemoembolization with continuous intra-arterial infusion chemotherapy, an
      response rate of 64% has been achieved in cases of unresectable hepatic
      metastases of colon cancer. These successful cases were reported along with
      personal comments by the authors.

PMID- 7802467
TI  - [The urologist in ambulatory care].
AB  - Although it is widely extended, outpatient urological practice is rarely referred
      to in the scientific publications. Our experience in the outpatient center is
      presented. The characteristics of the outpatient, the facilities of the area
      where we practice and the unique doctor-patient relationship are described. A
      proposal is made to provide a wide range of diagnostic and therapeutic urological
      services at the outpatient centers.

PMID- 7802468
TI  - [Abnormalities of the inferior vena cava: the retrocaval ureter].
AB  - We report three cases of retrocaval ureter with a clear indication for surgery:
      one patient with severe hydronephrosis and two cases with mild dilatation of the
      renal pelvis, calyces and upper ureter, both complicated by renal stones. The
      initial diagnosis was based on the ultrasound and the intravenous urogram
      findings, and was confirmed by a retrograde pyelogram in combination with
      cavography and CT. All patients were submitted to surgery (1 nephrectomy and 2
      uretero-ureteric anastomosis). Renal stone was resolved at the same time in one
      case, and by ESWL after surgery in the other.

PMID- 7802469
TI  - [Testicular tumors: our follow-up and treatment protocol. Report of 30 cases].
AB  - The high incidence of testicular tumors seen in our setting prompted us to review
      our therapeutic and follow-up protocols and assess patient survival and course
      within the period spanning June, 1989 to August, 1992. During this 38-month
      period, we diagnosed a total of 30 cases (15 seminoma, 2 pure embryonal
      carcinoma, 8 mixed embryonal, 3 lymphoma and 2 Leydig cell tumors). Apart from
      orchidectomy, we utilized radiotherapy, chemotherapy and resection of residual
      tumor mass, according to the histological type and tumor stage. Of the 15
      seminomas, there was 1 death (6%), 9 cases (60%) are tumor free with a mean
      survival of 25 months, and 5 cases (34%) are in partial remission at 11.3 months
      mean follow-up. Of the 10 nonseminomatous tumors, there was 1 death (10%), 5
      patients (50%) are in complete remission at 23.6 months (mean), 3 (30%) are in
      partial remission at 19.3 months (mean) and 1 (10%) is in frank progression as
      manifested by the unresectable masses of the retroperitoneal lymph nodes. The
      survival rate for the seminoma group was 94% and 90% for the nonseminomatous
      tumors.

PMID- 7802470
TI  - [Prognostic significance of epidermoid metaplasia in urothelial carcinoma of the
      bladder].
AB  - A retrospective review of 186 cases of transitional cell carcinoma of the bladder
      observed between 1987 and 1990 is described. Squamous metaplasia was present in
      37 cases. This histological feature was especially found in association with
      poorly differentiated and invasive tumors: the presence of extensive areas of
      squamous metaplasia (metaplastic areas = or > 50% of neoplastic surface) was
      always found in association with high grade neoplasms. For these reasons the
      authors conclude that transitional cell carcinoma of the bladder showing squamous
      metaplasia is more aggressive than pure transitional cell carcinoma.

PMID- 7802471
TI  - [Tumors of the female urethra: difficulties in the early diagnosis].
AB  - There is no widespread agreement on the treatment of tumors of the female urethra
      due to their scant incidence. These are generally slowly growing tumors with no
      salient or specific symptoms and signs. They manifest late and can be
      misdiagnosed as urethral lesions mimicking a tumor, therefore a biopsy is
      warranted. For all the foregoing reasons, these tumors are diagnosed in the
      advanced stages, with a worse prognosis despite very aggressive therapies. Two
      such cases are described: one was a Grabstald stage C3 epidermoid carcinoma that
      was submitted to anterior pelvic exenteration and died at 6 months, and the other
      was a Grabstald stage D4 papillary adenocarcinoma that died a few days after a
      resection biopsy. Due to the lower incidence of urethral adenocarcinoma, we
      review the literature on this tumor type and highlight its greater predisposition
      to progression which carries a worse prognosis.

PMID- 7802472
TI  - [Adverse reactions following transurethral resection of the prostate.
      Etiopathogenic considerations and report of a case of transient amaurosis]].
AB  - CNS changes following transurethral resection of the prostate are uncommon, but
      not insignificant. The foregoing condition may result from different causes
      including hemolysis, hyponatremia, brain edema, the use of atropine, or even
      postoperative vascular accidents, transient blindness being one of the most
      striking symptoms. The different etiologies are reviewed and a case of transient
      amaurosis, which we ascribe to brain edema, is analyzed. We underscore the
      importance of a detailed examination by the different specialists in order to
      institute the appropriate treatment and benefit patient recovery.

PMID- 7802474
TI  - [Penile prosthetic implant in the treatment of impotence: our experience].
AB  - The aim of this study was to review the current situation of penile prostheses in
      the treatment of erectile dysfunction and to analyze the indications, degree of
      acceptability and complications in our experience. From 1987 to 1993, 35 implants
      were inserted in men suffering from impotence due to different etiologies. The
      mean age was 54 years and the mean duration of erectile dysfunction was 37
      months. Diabetes, vascular disease and pelvic surgery were the most common
      pathologies recorded. We utilized the penoscrotal approach in 97.14% of the cases
      and implanted the following prostheses: 12 Hydroflex, 7 Uniflate 1000, 6 Acuform,
      4 Mark II, 3 Dynaflex and 3 Alpha 1. The mean follow-up was 38 months. Infection
      of the prosthesis by Staph. epidermidis was observed in 5.71% of the cases. This
      infectious complication required removal of the prosthesis. Two patients with a
      Uniflate prosthesis complained of mechanical failure. Eighty percent of the
      patients and 74.28% of their partners were satisfied with the results. When asked
      if they would undergo another operation again if it were necessary, 71.42%
      answered "yes". Penile prostheses have withstood the test of time and continue to
      be an effective and valid therapeutic alternative in impotent men. Although the
      complication rate is low, adequate information must be provided to the patient
      and partner in order to enhance the results.

PMID- 7802473
TI  - [No-scalpel vasectomy].
AB  - No scalpel vasectomy (NSV) is a new and refined technique with advantages over
      the conventional incisional technique. It requires no incision, no stitches; it
      is faster to perform and with less complications, and is equally effective. We
      present our experience in 100 patients submitted to NSV. The technique is
      described herein, as well as the anesthetic procedure and the instruments
      required for NSV.

PMID- 7802475
TI  - [Stress urinary incontinence. Comparative study of suprapubic and vaginal
      surgical techniques].
AB  - We compared the results achieved by the suprapubic techniques of bladder neck
      suspension (Marshall-Marchetti-Krantz and Burch) and the vaginal techniques (Raz
      I and II) in 31 patients. Although no significant difference was observed in the
      results achieved, the vaginal techniques require a shorter operating time and
      hospitalization. There were 5 cases of inability to void (3 for the suprapubic
      and 2 for the vaginal techniques). The following complications were observed in
      the Burch colposuspension technique: 1 bladder fistula, 1 ureteral obstruction, 1
      incisional hernia and 1 pulmonary embolism. We can conclude that although both
      techniques achieve good results, the vaginal techniques are easy to perform and
      require a shorter operating time and hospitalization.

PMID- 7802476
TI  - [Digestive hemorrhage in renal cell carcinoma].
AB  - We report a rare case of a young male patient with a single duodenal metastasis
      from a renal cell tumor nine years after nephrectomy that presented as upper GI
      tract hemorrhage. The clinical and pathological aspects of this uncommon
      intestinal metastasis are briefly discussed.

PMID- 7802477
TI  - [Well-differentiated liposarcoma of the spermatic cord with dedifferentiation].
AB  - We report a case of well-differentiated liposarcoma with dedifferentiation of
      spermatic cord in a 73-year-old-man. Treatment was by orchiectomy without
      retroperitoneal lymph node dissection or adjuvant therapy. The patient has
      survived 10 months with no evidence of recurrence. Liposarcoma localized to the
      spermatic cord is rare; less than 70 cases have been previously reported. The
      literature is reviewed with special emphasis on the clinical significance of the
      dedifferentiation phenomenon.

PMID- 7802478
TI  - [Wunderlich syndrome secondary to rupture of acquired cystic kidney].

PMID- 7802479
TI  - [Recurrent retroperitoneal malignant fibrous histiocytoma of myxoid type with
      mesocolon infiltration].
AB  - Malignant fibrous histiocytoma is an uncommon soft tissue sarcoma. If located in
      the retroperitoneum, abdominal pain is the predominant clinical feature. Like all
      primary tumors in this area, it is difficult to diagnosis early. A case of
      malignant myxoid retroperitoneal fibrous histiocytoma is described. Six years
      after it had been resected, the tumor recurred and infiltrated the mesocolon. The
      patient was submitted to intestinal resection. Although this tumor type carries a
      poor prognosis, patient survival is longer and there are less metastases.

PMID- 7802480
TI  - [Adrenal epithelial cyst of embryonal vestiges].
AB  - A 10 x 6.5 cm cyst with ciliated cell lining was removed from a 43-year-old
      woman. The immunohistochemical studies demonstrated that the cyst cells expressed
      keratins (Lu 5+) and the adrenal cortical cells did not, suggesting that the cyst
      lining was not derived from adrenal cells. The presence of ciliated cells
      indicates that the cyst was derived from embryonal vestiges.

PMID- 7802481
TI  - [Ultrasonography diagnosis of ureteral ectopy in prostatic urethra].
AB  - A 54-year-old male who consulted for an episode of right-sided nephric colic is
      described. A urological ultrasound scan disclosed grade I hydronephrosis in the
      upper half of the right kidney and an anechoic tubular image ending in the
      prostate gland. A subsequent urographic evaluation confirmed the diagnosis of
      ectopic ureter in prostatic urethra.

PMID- 7802482
TI  - [Penile incarceration at its base with metallic object].
AB  - Herein we describe a case of penile incarceration due to a nut at the base of the
      penis which was resolved by cutting the metallic object. The literature on penile
      strangulation describes different foreign bodies and methods of management of
      constrictive penile band injury.

PMID- 7802483
TI  - Renal carcinoma: clinical, diagnostic and prognostic aspects.
AB  - The purpose of this study was to review the clinical records of 103 patients with
      renal cell carcinoma and analyze the frequency of the most important signs and
      symptoms, as well as the tumor relationships with the morphologic
      characteristics. The differences in frequency were significant for signs and
      symptoms and tumor size (p<0.01) and signs and symptoms and disease stage
      (p<0.01) and were not significant (p<0.05) for signs and symptoms and
      histological pattern. The mode of clinical presentation of renal cell carcinoma,
      its implications in surgical strategy and the clinical prognostic factors are
      also considered.

PMID- 7802484
TI  - Proceedings of the Euroleish IV workshops. Epidemiology, health strategies and
      tools in leishmaniasis. Tunis, Tunisia, 15-20 May 1993. Proceedings.

PMID- 7802485
TI  - Molecular approaches applied to the epidemiology of leishmaniasis in Venezuela.
AB  - Leishmaniasis is on the increase in Venezuela (ca 30,000 new cases per year) due
      to deterioration in health management, increased risk groups among
      inmunosuppressed individuals and increased human penetration into the ecological
      habitats of sandfly vectors. An STD2-funded project (1989-1992) focused on the
      Andean state of Tachira, which showed the highest annual index of new cases (ca
      200-250). The project aimed at contributing to vector/parasite identification
      through a combination of molecular and well established field techniques: Newly
      developed molecular methods distinguished among Lu. spinicrassa, Lu. youngi and
      Lu. townsendi. These three species of the Verrucarum group are sympatric in the
      Northeast of the state and could be successfully identified by CHA, DNA probes
      and RAPD. A Le. braziliensis specific KDNA probe used with squash blots indicated
      that Lu. spinicrassa is the main vector and that Le. braziliensis is the main
      parasite species in Tachira state, Venezuela. PCR and the Le. brasiliensis
      specific DNA probe, schizodemes, isoenzymes and polyclonal antibodies agreed as
      taxonomic criteria for classification of Leishmania isolated from
      parasitologically confirmed cases in Tachira. Considerable degree of antigen
      heterogeneity in Venezuelan Le. braziliensis complex and Le. mexicana complex
      isolates from Tachira suggests multiple candidate antigens for improving the
      specificity of immunological diagnosis. The methods developed and tested in
      Tachira state should be valuable in order to help solving other outstanding
      epidemiological problems such as following of the epidemiological impact of
      intervention and vector control measures in highly endemic areas. Future work
      (STD3 funded, 1993-1996) aims to apply these molecular techniques to a vector
      control pilot study in Lara state, an area showing the highest incidence of new
      cases in the country.

PMID- 7802486
TI  - The characterization of Leishmania parasites and their vectors from Central
      America using molecular techniques.
AB  - The disfiguring cutaneous and mucocutaneous and often fatal visceral forms of
      leishmaniasis are an increasing public health problem in Central America. There
      are some evidences of a highest prevalence of L. braziliensis and L. mexicana in
      Guatemala; L. braziliensis, L. panamensis and L. infantum (L. chagasi) in
      Honduras and Nicaragua, and L. panamensis in Costa Rica and Panama. Our research
      project, just starting, attempts to use molecular approaches for a more rapid and
      accurate diagnosis and to identify the parasites. The techniques include non
      radioactive DNA probes, PCR, schizodeme, isoenzyme analysis and monoclonal
      antibodies; and specific recombinant peptides will be used to improve
      immunodiagnosis of the visceral form. Intra-specific heterogeneity in Leishmania
      isolates will be examined by pulsed field electrophoresis and random amplified
      polymorphic DNA. Using selected strains, the techniques will be compared on a
      regional basis leading to a better knowledge of parasite distribution and the
      related clinical entities. Furthermore, DNA probes for the identification of
      parasites in vectors and for sibling species of vectors, are also to be applied;
      chemical identification of sandfly male pheromones will be attempted possibly
      leading to potential novel control measures.

PMID- 7802487
TI  - Sensitivity and specificity of a recombinant Leishmania chagasi antigen in the
      serodiagnosis of visceral leishmaniasis.

PMID- 7802488
TI  - Applicability of direct agglutination test (DAT) at a rural health setting in
      Bangladesh and feasibility of local antigen production.
AB  - As part of a large-scale sero-epidemiological survey on visceral leishmaniasis
      (VL) carried out in Mymensingh district of Bangladesh, applicability of DAT was
      assessed at the level of a rural health setting in Trishal (upazila) subdistrict.
      Despite the relatively less optimal conditions encountered, 5854 inhabitants from
      7 villages appendant to Trishal were assessed for VL. The demographic
      distribution for sero-positivity obtained at the rural setting was comparable to
      that found by DAT as executed at the central laboratory (IEDC&R, Dhaka) on 9619
      inhabitants from the same upazila. The overall sero-prevalence rate was 4.4%
      compared to 3.7% obtained in the population assessed at the central laboratory.
      In either study, similar VL prevalence rates of 2.1% were obtained in the male
      populations. Irrespective of sex, younger population (< 20 years) in both studies
      appeared to have higher VL incidence rate (2.3% and 2.6%) than others of 21- > or
      = 90 years (1.4% and 1.8%). Local production of DAT antigen employing an
      authochtonus L. donovani isolate was attempted at the central laboratory (IEDC&R)
      in Dhaka. By comparison with the reference antigen, titres obtained in all 33 VL
      sera tested were equally higher (1:6400- > or =: 51200) than in 35 out of 38
      negative controls (< or = 1:400-1:1600). A comparable level of reactivity was
      also obtained in 53 VL and 52 negative control sera using a well characterized L.
      donovani strain (MHOM/IN/80/D88) from India. However, unlike the reference
      strain, titres obtained in 7 endemic controls were significantly higher with the
      authochtonous and homologous antigen (1:3200 - 1:6400) than with the reference
      (1:100 - 1:1600). The results signify the advantage of employing indigenous L.
      donovani isolates to further improve DAT sensitivity for detection of early and
      sub-clinical VL.

PMID- 7802489
TI  - Epidemiology of leishmaniasis in Portugal.

PMID- 7802490
TI  - Risk factors for visceral leishmaniasis: role of Epstein-Barr virus infection.

PMID- 7802491
TI  - DNA probes development in Tunisia for the identification, the taxonomy and the
      eco-epidemiology of Old World Leishmania species.

PMID- 7802492
TI  - Leishmania and the clonal theory of parasitic protozoa.

PMID- 7802493
TI  - Environmental manipulation in the control of a zoonotic cutaneous leishmaniasis
      focus.
AB  - An investigation is currently underway to assess the efficiency and practicality
      of combined burrow destruction and removal of chenopods in the control of a
      zoonotic cutaneous leishmaniasis (ZCL) focus. Karameh and Sweimeh, situated in
      the southern Jordan Valley, are stable endemic foci for ZCL. Control measures
      have been initiated in Karameh and will be maintained for two years. Sweimeh will
      be used as control. Karameh combines a desert habitat with a high water table
      created by extensive irrigation. This resulted in an unnatural abundance of
      chenopods and active rodent colonies throughout the year. Some 50 Psammomys
      obesus and 6 Meriones tristrami were captured from various colonies. At present,
      chenopods are being uprooted and burrows destroyed to a depth of 0.5 to 1 meter
      within a perimeter of 2 Km from Karameh. However, man-made changes of the
      topography has made the application of control measures more difficult. The
      effect of control will be assessed through comparison of leishmanin skin tests
      (LST) positivity in children below the age of six years, from both foci, prior to
      and post control. Precontrol LST have shown a positivity rate of 33.3% in Karameh
      and 80.2% in Sweimeh.

PMID- 7802494
TI  - Antibodies to Leishmania (L) glycolipids and gangliosides in sera of patients
      with visceral or with zoonotic L. major leishmaniasis.

PMID- 7802496
TI  - Visceral leishmaniasis in Teresina, n. e. Brazil: towards a DNA probe kit and its
      adaptation to processing blood-contaminated samples.
AB  - The Lmet2 chemiluminescent DNA probe is a valuable tool for identifying parasites
      of the Leishmania donovani -complex in sand flies, dogs and human samples. Recent
      blood meals in sand flies or blood contamination of tissue samples inhibited
      probe sensitivity, whether radiolabelled or chemiluminescent detection systems
      were used. Treatment of membranes with protease before hybridisation restored
      positive signal. Alternatively samples could be lysed with protease and applied
      to membranes with a vacuum blotting apparatus. The Lmet2 protocol provides the
      basis for a DNA probe kit that is adaptable for use with a wide range of other
      probes.

PMID- 7802495
TI  - Genes coding for antigens recognized by sera from Andean cutaneous leishmaniasis
      patients from Peru.

PMID- 7802497
TI  - Development and application of the polymerase chain reaction for the detection
      and identification of Leishmania parasites in clinical material.
AB  - Detection, diagnosis and identification of Leishmaniasis may be difficult owing
      to low numbers of parasites present in clinical samples. The PCR has improved the
      sensitivity and specificity of diagnosis of several infectious diseases. A
      leishmania specific PCR assay was developed based on the SSUrRNA genes which
      amplifies DNA of all Leishmania species. Point mutations occurring within the
      rRNA genes allow differentiation of the Leishmania complexes using primers
      constructed with the 3/ ends complementary to the specific point mutations
      present in the SSU rRNA genes of the Leishmania species. Biopsy material, blood,
      lesion impressions and blood spots on filter paper can be used in the assay. In a
      longitudinal study on the incidence rates of VL, subclinical cases and PKDL in an
      endemic region of Sudan, filter paper blood spots from proven and suspected VL
      patients, PKDL and control samples from an endemic region in Sudan are being
      taken. The blood spots were analyzed in the DAT and by PCR and results compared
      with clinical and parasitological data. The first results indicate that the PCR
      on blood spots is a simple and sensitive means of detecting active VL; in PKDL
      patients parasites are detectable in the skin.

PMID- 7802498
TI  - [Phlebotomus: natural populations and population genetics].

PMID- 7802499
TI  - Leishmaniasis in the lowlands of Bolivia, prevalence of the disease in two groups
      of localities with different settlement ages in Carrasco Tropical, Cochabamba.
AB  - The invasion of the Bolivian Jungle has brought the new colonists some unfamiliar
      diseases, among which we study Leishmaniasis. A previous study described the
      situation in Yapacani. Departamento of Santa Cruz, a primary rain forest lowland
      area. We now focus on the characteristics of Carrasco Tropical, close to a hilly
      territory of the andean mountains. We studied 11 localities ("colonies") grouped
      as unions with different lengths of residence in the area. We considered males
      and females over 15 years old as "at risk" and studied in them all forms of
      leishmanial infection, through clinical and laboratory (smears) means, including
      the Montenegro Skin Test (IDRM). Cutaneous ulcers and scars were seen in 2.9% (10
      patients of 339 at risk, 6 from "27 de octubre", a younger settlement, 4 from the
      older Tamboradas): mucocutaneous lesions in 3 (1 from the younger settlement);
      and skin scars alone in 10.3% (35 from the younger area). The only 2 females with
      positive findings in the study were seen in this latter group. Transmission is
      apparently associated with the primary forest which exists at the foot of the
      Andes in the area, which is visited preferentially by young men.

PMID- 7802500
TI  - Leishmaniasis in the lowlands of Bolivia. Entomological studies on sandflies of
      the "Valle del Sacta". Tropical Carrasco of the Department of Cochabamba.
AB  - Up to 1987, through the LEISHBOL project (CEE-STD1) studies on sandflies were
      performed in the rain forests of Yapacani, a region of the Department of Santa
      Cruz. In another set of studies, also carried out within the LEISHBOLPE project
      (CEE-STD2), sandflies were studied in the rain forests of the "Valle del Sacta,
      Prov. Carrasco" of the Departament of Cochabamba, to determine the composition of
      the species, its density, the anthropophilic species, and its infection by
      flagellates. 18 species were identified, from those collected in the Valle del
      Sacta, one of which was a new species now being described as Lutzomyia lerayi n
      sp. Only 7 species are common with those identified in Yapacani, in spite of the
      proximity and of the apparent similarity of the biotopes. Lu. shawi was the only
      species captured practically year round, and highest densities were identified in
      October with 7.6 "females/hour/shannon trap". The lowest monthly density occurred
      in July with "0.2 female/hour/shannon trap." In relation to the altitudinal
      density of Lu. shawi, it was higher at 5 meters (5.5 females/night/CDC in
      October) than at 1 meter (2.3 females/night/CDC-trap in November) above ground
      level. The following species was detected as anthropophilic: Lu. shawi, Lu.
      amazonensis, Lu. evangelistai and Lu. sherlocki. 4.5% (7 of 154) of Lu. shawi
      were found to be infected by flagellates in suprapiloric position. The
      composition of the sandfly species of Valle del Sacta is different than that of
      Yacapani. The most important species of Valle del Sacta is Lu. shawi, instead of
      Lu. yucumensis of Yapacani.

PMID- 7802501
TI  - Leishmaniasis in Lybia and studies on sandflies.

PMID- 7802502
TI  - Preliminary observations on the diagnosis and transmissibility of canine visceral
      leishmaniasis in Teresina, n.e. Brazil.
AB  - A pilot group of 49 dogs and control groups from non-endemic areas were examined
      serologically for the presence of visceral leishmaniasis (VL) by direct
      agglutination test (DAT), indirect immunofluorescence (IFAT) enzyme-linked
      immunosorbent assay (ELISA) and DOT-ELISA. Results indicated that DAT is less
      sensitive than the other assays and that serology with filter paper blood samples
      is less sensitive than with serum. Promastigote infections were common in fed
      Lutzomyia longipalpis taken from a dog kennel inhabited by a dog carrying
      Leishmania chagasi. Colony-bred Lu. longipalpis readily acquired L. chagasi
      infection when fed on skin lesions of dogs naturally infected with L. chagasi: a
      small proportion of flies also became infected when fed on apparently normal
      skin. Widespread distribution of amastigotes in normal skin of asymptomatic
      animals was shown both by intensive microscopy and by probing skin biopsy samples
      with the Lmet2 L. donovani-complex specific DNA probe. It was demonstrated that
      an immunologically naive dog could be infected by a single experimentally
      infected sand fly. Abundant amastigotes present within the resultant lesion 22
      days later were transmissible to sand flies but serology remained negative at
      least 45 days after the infective bite. Experimental transmission of canine VL by
      sand fly bite is a valuable approach for determining which diagnostic procedures
      are most sensitive, specific and suitable for field application in suburban
      households.

PMID- 7802503
TI  - Demonstration of natural Leishmania infection in asymptomatic dogs in the absence
      of specific humoral immunity.
AB  - Asymptomatic dogs from a Kala-Azar endemic region were screened for infection
      status by parasitological, immunological and molecular techniques. Bone marrow
      was examined for the presence of parasites by NNN culture and by using the Lmet 2
      DNA probe. All the samples were negative in culture but 24 of 41 were positive as
      determined by the probe. Cellular and humoral immunity were detected by T cell
      proliferation assays and IFAT respectively. Specific cellular and humoral
      immunity were found in 20 and 26 dogs respectively out of a total of 41 dogs
      examined. The vast majority of dogs with Leishmania-specific antibodies were
      found to be parasitologically positive using the DNA probe while almost half
      those that had demonstrable cellular immunity were apparently parasite free. The
      observation that dogs can develop cellular immunity following natural infection
      clearly indicates that there is a spectrum of canine leishmaniasis similar to
      that observed in the human disease. The prevalence of dog leishmanial infection
      must also be higher than was presumed.

PMID- 7802505
TI  - Epidemiological aspects of the leishmaniasis in Central America.

PMID- 7802504
TI  - A focus of visceral and cutaneous leishmaniasis on the northern coast of
      Colombia.

PMID- 7802507
TI  - PCR: a tool for diagnosis of American tegumentary leishmaniasis in a health post
      of rural endemic areas.

PMID- 7802506
TI  - The squash blot technique and the detection of Leishmania major in Phlebotomus
      papatasi in Tunisia.
AB  - This study describes the preliminary applications of the squash blot technique in
      Tunisia, to detect Leishmania major in naturally infected Phlebotomus papatasi.
      309 P. papatasi among 364 female sandflies squashed on to nylon Gene Screen DNA
      transfer membranes, were identified using the 3.2 kb ribosomal P. papatasi
      specific DNA probe described by Ready et al. A second hybridization using the
      Taq1 DNA probe described by Smith et al. (1989) allowed the detection and
      identification of the parasite in 15 (4.9%) of these P. papatasi specimens. The
      dissection of P. papatasi females during the same period and from the same
      biotopes showed an infection rate of 7.9% (9 positives among 113 dissected). The
      t proportion comparison test indicated that there is no significant statistical
      difference between the dissection and the squash blot technique for the
      estimation of infection rates of P. papatasi.

PMID- 7802508
TI  - From pulsed field to field: contribution of molecular karyotyping to
      epidemiological studies on New World leishmaniasis.

PMID- 7802509
TI  - Screening for drinking problems by patient self-report. Even 'safe' levels may
      indicate a problem.
AB  - BACKGROUND: Physicians often screen their ambulatory patients for serious
      drinking problems by asking questions related to the quantity of alcohol that
      they consume. Never previously reported is whether this "quantitative" approach
      to screening can be used to effectively screen ambulatory patients for the
      presence of a serious drinking problem. METHODS: The project interviewed 510
      patients attending an inner city general medicine practice with the alcohol
      module of the Diagnostic Interview Schedule, revised for the Diagnostic and
      Statistical Manual of Mental Disorders, Revised Third Edition. Collected data
      also included reported quantity, frequency, and recency of drinking. We then
      calculated the sensitivity, specificity, positive predictive values, and receiver
      operating characteristic curve for zero to two, three to five, six to 11, 12 to
      23, and 24 or more standard drinks as reported by 155 patients who reported
      drinking within 30 days of their visit. RESULTS: Forty-eight of 155 active
      drinkers met the Diagnostic and Statistical Manual of Mental Disorders, Revised
      Third Edition criteria for alcohol dependence or abuse. Only five patients with
      an active diagnosis failed to report drinking within 30 days of their visit. The
      calculated area under the receiver operating characteristic curve for reported
      quantity was 0.81. The sensitivities of reported consumption decline with
      increasing drinking, while the specificities and positive predictive values rise.
      The report of drinking between six and 12 drinks per week was associated with a
      positive predictive value of 0.54 for an active Diagnostic and Statistical Manual
      of Mental Disorders, Revised Third Edition, diagnosis. CONCLUSIONS: Patient self
      report of drinking can be used to screen actively drinking outpatients on the
      general medicine service for serious drinking problems. Further, in an urban
      general medicine outpatient population, even federally recommended levels of
      drinking may indicate a problem. Our data suggest that physicians'
      recommendations be adjusted for the setting in which they practice.

PMID- 7802510
TI  - Systemic embolization complicating right ventricular myocardial infarction.
AB  - We describe a patient in whom multiple episodes of pulmonary and systemic
      embolization occurred in the setting of right ventricular infarction. The
      mechanism of paradoxical embolization was determined based on transesophageal
      echocardiographic findings that included right atrial spontaneous contrast,
      appendage thrombosis, patent foramen ovale with right-to-left atrial shunting,
      and absence of left ventricular thrombosis. Recurrent thromboembolization was
      prevented by percutaneous placement of a "clam-shell" occluder across the patent
      foramen. This clinical scenario may be more common than previously believed and
      is best detected with transesophageal echocardiography. Early identification of
      this condition can lead to prompt treatment and prevention of subsequent
      thromboembolic morbidity.

PMID- 7802511
TI  - Acute renal failure attributable to ciprofloxacin in a patient with the acquired
      immunodeficiency syndrome.

PMID- 7802512
TI  - Clinical impact of inaccuracies in anticoagulation monitoring.

PMID- 7802513
TI  - Cutaneous reactivity in tubercular lymphadenitis.

PMID- 7802514
TI  - Patient self-determination and advance directives.

PMID- 7802515
TI  - Methods for standardizing intravenous heparin therapy.

PMID- 7802516
TI  - Quality of death after discontinuation of dialysis.

PMID- 7802517
TI  - Cholesterol-lowering diets. A review of the evidence.
AB  - To evaluate the efficacy of the high-risk approach and the population approach
      for cholesterol lowering, large trials of dietary intervention (n > or = 150) and
      smaller trials of angiographic assessment of the impact of diet on coronary
      disease were reviewed. Two trials of dietary therapy as intensive individualized
      counseling in individuals at usual risk for coronary disease achieved 75% to 80%
      of the cholesterol lowering predicted by metabolic ward studies and produced a 5%
      to 14% reduction in total cholesterol levels. Four studies in high-risk
      individuals exceeded predictions and achieved a 4% to 17% reduction in total
      cholesterol levels. Similar efficacy was observed in six of the seven trials of
      diet for secondary prevention. Four trials employing the population approach
      achieved smaller but often significant reductions in total cholesterol levels of
      1% to 11%. No tachyphylaxis to dietary therapy occurred in trials in which
      dietary counseling was maintained during the trial. The effectiveness of diet is
      enhanced when individualized counseling is used, follow-up is maintained, and
      weight reduction is achieved.

PMID- 7802518
TI  - Ethical considerations in the allocation of organs and other scarce medical
      resources among patients. Council on Ethical and Judicial Affairs, American
      Medical Association.
AB  - Physicians' efforts on behalf of patients often involve the use of resources
      that, because of naturally limited supply or economic constraints, are not
      readily available to all who need them. The dilemma in such cases is how
      physicians may fulfill their ethical duties to "do all that [they] can for the
      benefit of the individual patient" when the care that they can provide is
      constrained by the scarcity of needed resources.

PMID- 7802519
TI  - Dialysis discontinuation. A 'good' death?
AB  - BACKGROUND: Approximately 10% of the deaths of patients receiving long-term
      dialysis for end-stage renal disease are preceded by discontinuation of dialysis.
      We prospectively studied the decision to discontinue dialysis and whether, as is
      often stated, these patients have a prompt, predictable, and comfortable death.
      METHODS: All patients receiving hemodialysis in a hospital-based and a
      freestanding unit whose long-term dialysis was discontinued in 1990 were included
      in the study. Patients, providers, and families of prospectively enrolled cases
      were interviewed to determine the reasons for discontinuation; the patients'
      terminal courses were reviewed daily to collect information describing their
      quality of death. Retrospectively enrolled cases were studied by chart review and
      interviews of providers. The reasons for discontinuation of dialysis and a rating
      of the quality of their deaths (for prospectively studied patients only) were
      determined by interdisciplinary team consensus. Quality of death was rated on
      scales of 1 (worst) to 5 (best) according to duration of dying, discomfort, and
      psychosocial circumstances. RESULTS: Eighteen patients discontinued dialysis
      after a mean duration of 43.6 months of hemodialysis, and they lived a mean of
      9.6 days after termination. The quality of death of the 11 patients who were
      enrolled prospectively was subjectively assessed as "good" (> 10 of a possible 15
      points) for seven patients and "poor" for four patients. A good quality of death
      was more likely if dialysis was discontinued because of medical deterioration
      from progressive chronic disease (P = .009); none of the three patients whose
      dialysis was discontinued for other reasons had a good death (P = .024).
      CONCLUSIONS: A majority of the prospective cohort of patients who discontinued
      dialysis experienced a good death by our largely subjective criteria. Improved
      palliative therapy for some of these dying patients, however, could have
      ameliorated prolonged suffering, delirium, and inadequately treated pain that led
      to a poor quality of death.

PMID- 7802520
TI  - An overview of trials of cholesterol lowering and risk of stroke.
AB  - BACKGROUND: While blood cholesterol level predicts coronary heart disease,
      whether there is any association with the risk of stroke is unclear. Some, but
      not all, observational studies suggest that cholesterol level predicts risk of
      stroke, particularly ischemic stroke. This hypothesis is attractive because
      ischemic events constitute the vast majority of all strokes and, like coronary
      heart disease, involve atherogenic processes. METHODS: To investigate whether
      lipid lowering reduces the risk of stroke, we performed an overview of randomized
      trials that included more than 36,000 individuals. RESULTS: The mean reduction in
      cholesterol level in the treated as compared with the control subjects ranged
      from 6% to 23%. Those assigned to treatment experienced no significant reduction
      in all (fatal plus nonfatal) stroke (relative risk, 1.0; 95% confidence interval,
      0.8 to 1.2) or fatal stroke (1.1; 0.8 to 1.6). CONCLUSIONS: The confidence
      interval for fatal stroke is wide, and alternative hypotheses, including either a
      small protective or harmful effect, cannot be excluded; however, the point
      estimates are compatible with no benefit of cholesterol lowering on the risk of
      stroke. Additional large-scale randomized trials assessing total mortality would
      more definitively address any benefits on stroke, as well as any excess
      nonvascular causes of mortality, for which risks of cholesterol lowering also
      remain uncertain.

PMID- 7802521
TI  - Risk factors that attenuate the female coronary disease advantage.
AB  - OBJECTIVE: To compare the coronary disease experience of men and women in a
      community setting. DESIGN AND SETTING: Prospective cohort study. PATIENTS: Long
      term follow-up of a population-based sample of 5209 men and women. RESULTS: Women
      outlive men and experience fewer cardiovascular events. By middle age, women lag
      20 years behind men in the incidence of myocardial infarction, but the gap closes
      in the elderly, when cardiovascular disease becomes the leading cause of death in
      women as well as in men. Menopause promptly escalates coronary disease risk
      threefold and greatly erodes the advantage over men. Women and men share the same
      major risk factors for coronary disease, although women experience a lower
      absolute risk. However, high ratios of total/high-density lipoprotein cholesterol
      level ratios, left ventricular hypertrophy, and diabetes tend to eliminate the
      female advantage. CONCLUSION: Coronary disease is not a minor problem in women.
      Consequently, women should take vigorous preventive measures. There is a need for
      particular attention to glucose tolerance and blood lipid levels and a greater
      sense of urgency when hypertension progresses to left ventricular hypertrophy.

PMID- 7802522
TI  - Morbidity and toxic effects associated with ganciclovir or foscarnet therapy in a
      randomized cytomegalovirus retinitis trial. Studies of ocular complications of
      AIDS Research Group, in collaboration with the AIDS Clinical Trials Group.
AB  - BACKGROUND: The Foscarnet-Ganciclovir Cytomegalovirus Retinitis Trial compared
      the use of either ganciclovir or foscarnet for the initial treatment of
      cytomegalovirus retinitis in patients with the acquired immunodeficiency
      syndrome. We previously reported that patients treated with foscarnet lived
      longer but were more likely to have their treatment switched, the latter
      suggesting foscarnet may not have been as well tolerated as ganciclovir. This
      study compared the morbidity and toxic reactions reported during the trial.
      METHODS: Two hundred thirty-four patients with the acquired immunodeficiency
      syndrome and previously untreated cytomegalovirus retinitis at 11 university
      centers were randomly assigned to receive intravenously either foscarnet (n =
      107) or ganciclovir (n = 127). Medical histories, laboratory tests, and drug
      treatment histories during the first 6 months of treatment were analyzed.
      RESULTS: Neutropenia was more common in patients assigned to ganciclovir than to
      foscarnet (34% vs 14%; P = .001). Patients assigned to foscarnet reported more
      infusion-related symptoms (58% vs 24%; P < .001) and, in male patients, more
      genitourinary symptoms (36% vs 16%; P > .001); they also experienced a trend
      toward more nephrotoxic effects (13% vs 6%; P = .082) and electrolyte
      abnormalities. The incidence of seizures was similar in both groups (foscarnet,
      12%; ganciclovir, 9%; P = .511). Patients assigned to foscarnet were more likely
      to be switched to the alternative treatment (foscarnet to ganciclovir, 46%;
      ganciclovir to foscarnet, 11%; P < .001), and most of this excess was
      attributable to toxic reactions. In 88% of cases in which treatment was switched
      as a result of toxic reactions and in which follow-up data were available, the
      toxic reaction resolved after the switch. No permanent disability or death
      resulted from toxic reactions. CONCLUSIONS: Compared with ganciclovir, the use of
      foscarnet was more frequently limited by the occurrence of toxic reactions.
      However, these toxic reactions rarely had long-term sequelae. In light of the
      previously reported survival benefit seen in patients treated with foscarnet,
      these data support the use of foscarnet for the initial treatment of
      cytomegalovirus retinitis.

PMID- 7802523
TI  - Occupational exposure among medical students and house staff at a New York City
      Medical Center.
AB  - BACKGROUND: The purpose of the study was to ascertain the prevalence of and
      reasons for underreporting of occupational exposures to patients' blood and body
      fluids among students and house staff. METHODS: A questionnaire surveyed 110
      medical students and 275 house staff members regarding the number of reported and
      unreported exposures to patients' body fluids, and the reasons why the
      respondents did or did not report their exposures during the previous 6 months.
      RESULTS: Of 385 surveys returned, representing a response rate of 60%, 122
      respondents (32%) experienced 330 occupational exposures during the previous 6
      months. Fifty-two percent of surgical house staff, 27% of students, and 20% of
      medical house staff were exposed. Whereas the exposure risk to surgical house
      staff increased with training, the risk to medical house staff decreased with
      training. Only 29% of exposed respondents reported an exposure. Exposures from
      sources known to be positive or at high risk for human immunodeficiency virus had
      the highest reporting rates. The most frequent reason for not reporting an
      exposure was that the patient was thought not to be infectious. Forty-six percent
      of respondents exposed to sources of unknown human immunodeficiency virus status
      who did not report chose "patient thought not to be infectious" as the reason.
      The most common reason for reporting an exposure was "hospital policy."
      CONCLUSIONS: Although limited by recall bias, this study showed that a high
      proportion of students and house staff experience occupational exposures. The
      results suggest that populations at high risk for exposures are the more
      experienced surgical house staff and the junior medical house staff. Exposures
      from sources known to be positive or at high risk for human immunodeficiency
      virus were reported more frequently than those from unknown risk sources.

PMID- 7802524
TI  - Nonulcer dyspepsia in a Dutch working population and Helicobacter pylori. Ulcer
      history as an explanation of an apparent association.
AB  - BACKGROUND: There is considerable debate about whether Helicobacter pylori
      infection is important in causing nonulcer dyspepsia. Many studies assessing this
      relationship have been performed in selected patient populations and included
      patients with a history of peptic ulcer. General population-based data with
      attention to ulcer history are needed to clarify this relationship. METHODS: A
      questionnaire on ulcer history and dyspeptic symptoms during the preceding 3
      month period was obtained from apparently healthy employees who underwent a
      periodic medical examination in the Netherlands. In addition, serum samples were
      analyzed for anti-H pylori IgG antibodies. RESULTS: A total of 427 men and 73
      women, aged 22 to 69 years, participated in the study. None of the women but 27
      men (6%) had a previous diagnosis of peptic ulcer. Among 19 unoperated-on men
      with verified duodenal (17 subjects) and gastric (two subjects) ulcer, 89% were H
      pylori positive, while 74% had frequent dyspeptic symptoms in the 3 months before
      the study. Among the 400 men and 73 women without an ulcer history, the 3-month
      period prevalence of frequent dyspepsia was 13% and 21%, respectively. The rate
      of H pylori positivity was 25% in subjects with nonulcer dyspepsia and 29% in all
      others. The H pylori infection rate increased with age and with a lower
      occupational level but was independent of gender. In the male population, various
      differences in symptoms between H pylori-positive and H pylori-negative subjects
      could be detected when the 27 subjects with a history of ulcer were included,
      whereas these differences disappeared when these subjects were excluded.
      CONCLUSIONS: In the Dutch working population, nonulcer dyspepsia is not related
      to H pylori infection, whereas for duodenal ulcer the relationship is clear. The
      apparent association between dyspeptic symptoms and H pylori infection is
      entirely accounted for by subjects with an ulcer history.

PMID- 7802525
TI  - Improving long-term prognosis for survivors of mechanical ventilation in patients
      with AIDS with PCP and acute respiratory failure. Five-year follow-up of
      intensive care unit discharges.
AB  - BACKGROUND: Before 1987, the hospital survival of patients with acquired
      immunodeficiency syndrome, Pneumocystis carinii pneumonia, and acute respiratory
      failure receiving mechanical ventilation was less than 15%. Hospital survival has
      improved since then, but concerns have been raised that the post-hospital
      discharge survival of these patients remains extremely poor. This study evaluated
      the long-term survival of patients discharged alive after an acute episode of
      acute respiratory failure caused by P carinii pneumonia. METHODS: A prospective
      cohort study was conducted for the 5-year period from May 1987 through May 1992
      in an urban teaching hospital. Forty-seven patients discharged from the hospital
      after receiving mechanical ventilation and/or continuous positive airway pressure
      for acquired immunodeficiency syndrome, P carinii pneumonia, and acute
      respiratory failure were followed up from their initial intensive care unit
      admission until death or termination of the study to measure the long-term
      survival and cumulative probability of survival of the study cohort. Actuarial
      life-table analysis was performed, and long-term cumulative probability of
      survival was calculated on the basis of the life-table analysis. Median survival
      was estimated by means of the product-limit method. RESULTS: During the 5-year
      follow-up of the 47 subjects, 31 patients died, 12 were unavailable for follow
      up, and four were still alive at the end of the cutoff. The cumulative survival
      rate at 1 year was 80% (95% confidence interval, 92% to 68%); at 2 years, 49%
      (95% confidence interval, 65% to 34%); at 3 years, 18% (95% confidence interval,
      32% to 4%); and at 4 years, 6% (95% confidence interval, 17% to 0%). Median
      survival time for all subjects was 602 days (1.65 years), and the longest
      survival time for a single patient was 1774 days (4.86 years). CONCLUSIONS: Post
      hospital discharge survival of patients with acquired immunodeficiency syndrome,
      P carinii pneumonia, and acute respiratory failure has improved dramatically in
      the past decade. Patients can undergo intubation and mechanical ventilation with
      the hope of reasonable long-term survival.

PMID- 7802526
TI  - [Predictive factors of primary success after coronary angioplasty. Qualitative
      and quantitative angiography of 3679 coronary stenosis before and after
      dilatation].
AB  - This study summarises the authors' experience of the prediction of primary
      success of coronary balloon angioplasty. A qualitative and quantitative
      angiographic study of 3679 coronary stenoses was undertaken before and after
      dilatation. Total occlusions before angioplasty and dilatations of saphenous vein
      bypass grafts were excluded. Two parameters were noteworthy: the occurrence of
      acute occlusion of the lesion during or immediately after angioplasty and the
      degree of residual stenosis as assessed by quantitative angiography. After
      multivariate analysis, 3 factors seemed strongly predictive of the risk of acute
      occlusion: the percentage stenosis before angioplasty, a left coronary artery
      stenosis and stenosis situated at the point of angulation of an artery.
      Quantitative angiographic studies identified 4 factors predictive of significant
      residual stenosis: the percentage stenosis before angioplasty, the irregularity
      of the contours of the lesion stenosis situated at the point of angulation of an
      artery and the presence of calcification. This study therefore shows at least two
      important discordances with the ACC/AHA morphological classification of coronary
      stenosis: firstly, excentricity would not seem to be a risk factor for primary
      failure of angioplasty and, secondly, excluding total occlusions, the percentage
      coronary stenosis before angioplasty as assessed by quantitative coronary
      angiography would seem to be the main predictive factor of both the risk of
      occlusion and the degree of residual stenosis.

PMID- 7802527
TI  - [A study of predictive factors of the operative risk in the surgery of aortic
      valve stenosis in aged patients].
AB  - Aortic stenosis, the most extensive form of valvular disease in elderly subjects,
      has become very common because of demographic reasons in industrialised
      countries. The operative risk in patients over 70 years of age is significantly
      higher. The progressive rise in age of patients referred for surgery justifies
      this analysis of predictive factors of operative mortality. Between 1976 and
      February 1993, out of 2871 aortic valve replacements, 675 (278 men and 397 women)
      patients were over 75 years of age and were included in this study. The average
      age was 78.5 +/- 3 years. Associated pathology was present in 226 patients. A
      bioprosthesis was chosen in 632 cases (93.6%). An associated surgical procedure
      was required in 133 cases. The operative mortality was 12.4 +/- 1.3% (84 deaths).
      Longitudinal analysis was performed for 4 successive periods to assess the
      outcome of the study population over the 17 years. A statistical study was made
      of 50 variables and multivariate analysis showed age (p < 0.0001), left
      ventricular failure (p < 0.0001), non sinus rhythm (p < 0.0005) and emergency
      procedures (p < 0.02) to be independent preoperative predictive factors of
      mortality. In order to reduce this risk, the authors recommend early surgical
      referral to avoid emergency procedures and cardiac failure, and increased efforts
      of myocardial protection during cardiopulmonary bypass. Despite the risk, surgery
      is the only radical treatment of aortic stenosis, including elderly patients.

PMID- 7802528
TI  - [Value of transesophageal echocardiography in the follow-up of successful
      percutaneous mitral valvotomy].
AB  - This study was undertaken to determine the value of transoesophageal
      echocardiography in the follow-up of patients with severe mitral stenosis having
      undergone successful percutaneous mitral commissurotomy as defined as a final
      valve surface area > 1.5 cm2 without > 2/4 mitral regurgitation (MR). Eighty one
      patients who had undergone successful procedures were studied by transthoracic
      (TTE) and transoesophageal echocardiography (TOE) before, immediately after (24
      to 48 hours) and at medium term (8 +/- 4 months) after balloon commissurotomy.
      The three main parameters studied were the degree of MR, presence of inter-atrial
      shunt and spontaneous left atrial contrast. Immediately after commissurotomy the
      MR was graded 0/4 in 6 patients (7.5%), 1/4 in 48 patients (59%) and 2/4 in 27
      patients (33.5%). The TOE showed small traumatic lesions (localised valve tears,
      rupture of an accessory chordae tendinae) in 9 cases (11%). At medium term follow
      up, the MR was stable in 75 patients (93%), decreased by one grade in 3 patients
      (3.5%), without the occurrence of severe MR. Interatrial shunts were more
      frequently observed by TOE than by TTE or oximetry with a prevalence of 57%. They
      usually disappeared at medium term follow-up. There were 3 factors associated
      with its persistence: a shunt visible at TTE, immediately after commissurotomy,
      visualisation of an atrial septal defect and a shunt jet width > or = 5 mm at TOE
      immediately after commissurotomy. Spontaneous contrast was common before the
      procedure (65%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7802529
TI  - [Long survival (an average of 7 years) after coronary bypass in patients with
      severe left ventricular dysfunction].
AB  - The inclusion criteria of this study were a left ventricular ejection fraction of
      less than 40% with global left ventricular hypokinesis; left ventricular
      aneurysms and valvular lesions were excluded. From January 1970 to December 1990,
      155 patients fulfilling these criteria had Class III or IV angina and 49 patients
      had Class II or III dyspnoea. The average left ventricular ejection fraction was
      31 +/- 7%. Over this 20 year period two surgical techniques were used: Group I
      (79 patients operated between 1970 and 1981) myocardial revascularisation with
      intermittent aortic clamping by an internal mammary artery pedicle on the left
      anterior descending artery and simple venous bypass grafts; Group II (76 patients
      operated between 1982 and 1990) myocardial revascularisation under oxygenated
      cardioplegia by internal mammary artery pedicle on the left anterior descending
      artery associated with sequential venous bypass grafts. The average number of
      bypass grafts was 1.6 in Group I and 3.7 in Group II (p = 0.001). The early
      postoperative mortality (first month) was 5.2% it was lower in Group II (2.6%)
      than in Group I (7.6%) (p = 0.01). After 79 +/- 14 months follow-up, 6 patients
      were lost to follow-up, 51 patients had died secondarily and there were 90
      survivors. Globally, 80% of deaths were of cardiac origin, 38% from cardiac
      failure. The actuarial 5, 10 and 15 year survival rates were 79 +/- 7%, 63 +/-
      10% and 36 +/- 15% respectively. The 5 year survival in Group I was 71 +/- 10%
      compared with 88 +/- 8% in Group II (p = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7802530
TI  - [Electron microscopic comparison of the antithrombotic potential of 2 low
      osmolality iodine contrast media in percutaneous transluminal coronary
      angioplasty].
AB  - The antithrombogenic potentials of two low osmolality iodine contrast media,
      ioxaglate (Iox), an ionic product, and iopamidol (Iop), a non-ionic product, were
      compared in a multicentre, randomised, double-blind study in 64 patients
      undergoing percutaneous transluminal coronary angioplasty (PTCA) by scanning
      electron microscopy for the presence of thrombotic material on the guiding
      catheter (GC) and guide wires (GW). The procedure was strictly standardised:
      stable angina, type A coronary lesions; aspirin administration (at least 300 mg
      the day before and on the day of angioplasty); heparinisation (10000 IU at the
      beginning of the procedure); same GCs (Marathon Baxter 8F), same GWs (Veriflex
      USCI 0.014). The tips of the catheters and guide wires were scanned by an
      electronic microscope in a double-blind protocol. The scores for the number of
      erythrocytes (RBCs), platelets (PLs) and constituted thrombi (THi) were;
      thickness scored from 0 to 3, the % surface covered and an index of volume
      combining these two parameters. The clinical and angiographic characteristics of
      the 2 groups were strictly comparable. The time that the GCs and GWs were in the
      circulation were 30.0 +/- 2.3 vs 32.6 +/- 3.0 minutes for the former, and 18.6 +/
      1.8 vs 17.1 +/- 1.4 minutes for the later in the Iox and Iop groups,
      respectively (NS). An angiographic filling defect was not observed in any of the
      patients in the Iox group and in 4 patients (13%) in the Iop group (NS). The
      number of thrombotic elements observed on the GCs (RBCs, PLs, THi) was negligible
      in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7802531
TI  - [Contribution of myocardial biopsy and immunohistochemistry to the prognostic
      evaluation of cardiac amyloidosis].
AB  - The authors report four cases of cardiac amyloidosis, the diagnosis of which was
      confirmed by endomyocardial biopsy. They underline the value of immuno
      histological studies with labelling of the biopsy fragments with anti
      transthyretin and anti-light chain immunoglobulin antibodies. This approach
      provides a more precise typing of amyloidosis and a more accurate evaluation of
      the prognosis.

PMID- 7802532
TI  - [Chronic constrictive pericarditis. A retrospective study of a series of 84
      patients].
AB  - Chronic constrictive pericarditis still poses diagnostic and therapeutic
      problems. A series of 84 cases (59 men-25 women; men age: 46 years) operated
      between 1979 and 1989 at the Pitie Hospital was reviewed. The majority of
      patients (72%) were in functional Classes III or IV; 88% had clinical signs of
      right ventricular failure and 18% had anasarca. The average duration of symptoms
      before diagnosis was 20 months. Chest X-ray showed pericardial calcification in
      40% of cases. A characteristic dip-plateau pressure tracing was obtained in 76%
      of cases. A specific aetiology was only found in 36 cases (45%), only 12% being
      of tuberculous origin. A subtotal pericardectomy from phrenic to phrenic was
      carried out in 75 patients. The absence of planes of cleavage in 9 cases imposed
      a special operative technique consisting of "patchwork" sectioning of the
      visceral pericardium. The operative mortality was 2.3% (2 patients: pulmonary
      embolism and septicaemia). Non-fatal post-operative complications occurred in
      8.2% of cases (7 patients). The survival rate excluding operative mortality was
      94% at 3 years and 87% at 7 years. No patient was reoperated for recurrent
      constrictive pericarditis. At the last follow-up appointment, all patients were
      in functional Classes I or II. The authors conclude that the absence of specific
      symptoms, the low prevalence of the condition and the change in aetiology related
      to the decline in tuberculous infection make the diagnosis of chronic
      constrictive pericarditis very difficult. The diagnostic contributions of new
      imaging techniques such as CT and MR scanning should be assessed. This series
      confirms the efficacy of surgical treatment by subtotal pericardectomy.

PMID- 7802533
TI  - [Time changes of mitral regurgitant jets: a 4th dimension for Doppler evaluation
      of the severity of mitral regurgitation].
AB  - The quantitation of mitral regurgitation is based on measurement of the maximal
      jet area by colour flow mapping. Discrepancies have been reported with the
      possibility of significant temporal variations of jet size. The aim of this study
      was to determine whether evaluation could be improved by taking these variations
      into consideration. Three dimensional Doppler colour flow mapping by combining
      measurements of length, height and width of the jet in two orthogonal planes, in
      order to obtain a global index of regurgitation, was undertaken in 40 patients
      with angiographically documented mitral regurgitation classified in three
      degrees, mild, moderate and severe. Two-dimensional Doppler with colour M-mode
      was performed in each patient analysing early, mild and late systole. In the
      absence of significant temporal variation, assessment was based on measurement of
      maximal jet area alone (maximum global regurgitation index). When there were
      significant temporal variations, the index was calculated during each phase of
      systole and the values averaged to obtain a mean global regurgitation index.
      Temporal variations were observed in 14 of the 40 patients (35%), mainly in mild
      and moderate regurgitation. Significant differences were noted in the values of
      maximal (p < 0.01 to 0.001) and mean global regurgitation indices (p < 0.001 to
      0.0001) between each degree of severity. A paired study demonstrated significant
      differences between the two indices in mild (p < 0.01) and moderate regurgitation
      (p < 0.05). Assessment of the severity of mitral regurgitation was satisfactory
      in 65% of cases using the maximal global regurgitation index with 14
      overestimations, all in cases of mild and moderate regurgitation.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7802535
TI  - [Positive inotropic and lusitropic effect of RP 62719, a new class III
      antiarrhythmia agent].
AB  - Antiarrhythmic drugs, especially the Class I family, exert a negative inotropic
      effect on the myocardium which is particularly undesirable in patients with
      depressed left ventricular function. Therefore, research has been directed to the
      development of new, more specific molecules of the Class III family. The authors
      studies the mechanical effects of RP 62719 on guinea pig left ventricular
      papillary muscle. This new molecule is a pure Class III antiarrhythmic, known to
      lengthen the duration of the cardiac action potential by selectively blocking the
      potassium current iK1 (inward rectifier K+ current). The mechanical parameters
      were determined during the phases of contraction and relaxation under isotonic
      and isometric conditions. At 0.2 and 2 microM concentrations, RP 62719 improved
      cardiac contraction under both isotonic and isometric conditions with an increase
      of about 30% of Vmax (p < 0.001), the maximum unloaded shortening velocity delta
      1 (p < 0.001), the peak isometric active force normalized per cross-sectional
      area [AF/S (p < 0.001)]. At these two concentrations, a positive lusitropic
      effect (improved relaxation) was demonstrated by an increase in negative peak of
      derivative per mm2-dF/s and maximum lengthening velocity VR max (p < 0.01). At
      higher concentrations (20 microM), the inotropic and lusitropic effects were less
      marked with a bell-shaped form of the dose-effect curve. This study indicates
      that RP 62719 has moderate but significant positive inotropic and lusitropic
      effects. These actions could provide significant therapeutic advantages
      especially in patients cardiac failure.

PMID- 7802536
TI  - [Artefacts and intravascular ultrasonography. Analysis and implications for a
      better reliability in the interpretation of images and measurements].
AB  - Intravascular ultrasound catheters provide cross-sectional images of vessel walls
      and surrounding tissues with rotating transducers, and the behavior of ultrasound
      in heterogeneous media both cause degradation of image quality. Qualitative and
      quantitative analyses of in vivo studies are operator-dependent and limited by
      artifacts. We investigated these limitations by an in vitro study on plexiglass
      phantoms and segments of fresh arteries. We observed, analyzed and interpreted
      the most specific reasons for image artifacts: geometric distortions, the point
      spread function of the imaging system and the near field effects. Various
      practical implications have resulted from this study. Knowledge of the most
      obvious pitfalls will enable the user to obtain maximum benefits from
      intravascular ultrasound imaging, and to appreciate its limitations.

PMID- 7802537
TI  - [Mitral valve replacement with cryopreserved mitral homograft].
AB  - Mitral valve replacement using a cryopreserved mitral homograft was performed in
      a 49 year old patient with calcified mitral stenosis. The surgical technique is
      described. The postoperative course was uneventful. Transoesophageal echo
      performed 4 months later showed a normal function of the mitral homograft.

PMID- 7802534
TI  - [Malignant mesothelioma of the pericardium. An anatomo-clinical study of 10
      cases].
AB  - Ten pericardial mesotheliomas (8 of which had associated unilateral pleural
      involvement) were observed over a 22 year period in subjects over 50 years of
      age. The diagnosis was only confirmed several months after the presenting
      symptoms (shortness of breath, chest pain), usually by histological studies of
      pericardial biopsies performed during construction of a pleuro-pericardial window
      because of tamponade or of pleural biopsy in cases of pleuro-pericardial disease.
      There is no specific diagnostic feature and even modern imaging methods are
      unable to distinguish mesothelioma from pericardial tuberculosis. In 7 cases,
      there were large haemorrhagic pericardial effusions. At present, there is no
      effective treatment for mesothelioma and the physician's goal is to make the
      patient's short survival time as comfortable as possible with respect to the
      severe pain and recurrent pleuro-pericardial effusions. The pericardial
      mesothelioma is rare (less than 1% compared with 96% pleural and 3% peritoneal
      localisations) and possibly related to exposure to asbestos, at least in those
      cases with associated pleural involvement. The authors underline the utility of
      histological analysis of the utility of histological analysis of the pericardium
      if only to establish the diagnosis of mesothelioma and to enable administration
      of curative treatment of other pathologies (tuberculosis, malignant lymphoma)
      with identical clinical presentations.

PMID- 7802538
TI  - [Severe pulmonary hypertension complicating a long treatment with
      dexfenfluramine].
AB  - The authors report a case of severe pulmonary hypertension after long-term
      dexfenfluramine treatment in a 48 year old man with no previous medical history.
      Dexfenfluramine, which has previously been reported to cause pulmonary
      hypertension, is an amphetamine-like anorexic agent, a pharmacological group
      known to predispose to this type of side effect. The possibility of this
      complication should be born in mind before prescribing the drug. In particular,
      it would seem to be particularly important not to exceed the recommended length
      of treatment especially as potential reversibility of pulmonary hypertension on
      withdrawal of the drug has been reported in one case.

PMID- 7802539
TI  - [Phlebitis of the right upper limb and thromboembolic pulmonary hypertension.
      Apropos of a case of heart-lung transplantation].
AB  - The authors report the case of a 25 year old man with unexplained pulmonary
      hypertension during his first hospital admission. However, a past medical history
      suggesting right arm vein thrombosis was obtained. Venography showed signs of
      thoraco-brachial compression. After heart-lung transplantation, pathological
      studies of the explanted organs showed changes of thrombo-embolic pulmonary
      hypertension. A spontaneous right arm venous thrombosis occurred during
      convalescence. The possibility of post-embolic pulmonary hypertension caused by
      venous thrombosis of the upper limbs is discussed.

PMID- 7802540
TI  - [Surgical treatment of leiomyosarcoma of the left atrium Report of a case and
      review of the literature].
AB  - The authors report a case of left atrial leiomyosarcoma presenting with systemic
      disturbances and retinal emboli diagnosed by echocardiography and surgery in a 59
      year old woman. Surgical ablation was completed by a course of chemotherapy.
      Histopathological examination confirmed the diagnosis of sarcoma; although the
      patient remained generally well, severe mitral regurgitation appeared 21 months
      after surgery. Transoesophageal echocardiography revealed an abnormal, hyper
      mobile, intra-atrial echo suggesting a ruptured chordae tendinae and the mitral
      valves appeared very thickened and retracted. The patient was reoperated and the
      mitral valve replaced with a bioprosthesis. After a total follow-up of 29 months,
      the patients is still alive and asymptomatic. The authors underline the
      importance of echocardiography in the diagnosis of intra-cardiac tumours in
      general and, in particular, of intra-cardiac sarcomas.

PMID- 7802541
TI  - Chemical composition of lipopolysaccharides from Legionella bozemanii and
      Legionella longbeachae.
AB  - Lipopolysaccharides (LPS) from Legionella bozemanii serogroup 1 and Legionella
      longbeachae serogroup 1 were subjected to chemical analyses. The lipid A part of
      both LPSs contained 2,3-dideoxy-2,3-diamino-D-glucose as major constituents and D
      glucosamine and glycerol as minor constituents of the sugar backbone structure.
      Both LPSs exhibited a very complex fatty acid composition. Twenty amide-linked 3
      hydroxy fatty acids were detected in LPS of L. longbeachae, whereas seventeen
      were encountered in LPS of L. bozemanii. Both LPSs contained nine ester-linked
      nonhydroxy fatty acids and the unique long-chain fatty acids 27-oxo-octacosanoic
      acid, 29-oxo-triacontanoic acid, heptacosane-1,27-dioic acid and nonacosane-1, 29
      dioic acid. SDS-PAGE showed that L. bozemanii produced smooth-form LPS, whereas
      L. longbeachae LPS was mainly of the R-type. Composition analyses were in
      accordance with these electrophoretic patterns. D-Quinovosamine and L-fucosamine
      constituted 80 mol% of the polysaccharide part of L. bozemanii LPS. Other sugars
      identified were D-glucosamine, D-mannose, D-glucose, L-rhamnose, D-glycero-D
      manno-heptose, L-glycero-D-manno-heptose, 2-keto-3-deoxy-octonic acid and
      glycerol. The polysaccharide chain from LPS of L. longbeachae appeared to be
      shorter, but composed of the same sugars except L-fucosamine. Both LPSs contained
      glycerol phosphate and glucosamine phosphate and L. longbeachae LPS contained in
      addition glucose phosphate.

PMID- 7802542
TI  - Anaerobic growth of Salmonella typhimurium on L(+)- and D(-)-tartrate involves an
      oxaloacetate decarboxylase Na+ pump.
AB  - We show here that the Enterobacterium Salmonella typhimurium LT2 has the capacity
      to grow anaerobically on L(+)- or D(-)-tartrate as sole carbon and energy source.
      Growth on these substrates was Na(+)-dependent and involved the L(+)- or D(-)
      tartrate-inducible expression of oxaloacetate decarboxylase. The induced
      decarboxylase was closely related to the oxaloacetate decarboxylase Na+ pump of
      Klebsiella pneumoniae as shown by the sensitivity towards avidin, the location in
      the cytoplasmic membrane, activation by Na+ ions, and Western blot analysis with
      antiserum raised against the K. pneumoniae oxaloacetate decarboxylase.
      Participation of an oxaloacetate decarboxylase Na+ pump in L(+)-tartrate
      degradation by S. typhimurium is in accord with results from DNA analyses. The
      deduced protein sequence of the open reading frame identified upstream of the
      recently sequenced oxaloacetate decarboxylase genes is clearly homologous with
      the beta-subunit of L-tartrate dehydratase from Escherichia coli. Southern blot
      analysis with S. typhimurium chromosomal DNA indicated the presence of probably
      more than one gene for oxaloacetate decarboxylase.

PMID- 7802543
TI  - Isolation and structure elucidation of acinetobactin, a novel siderophore from
      Acinetobacter baumannii.
AB  - A novel siderophore, called acinetobactin, with both catecholate and hydroxamate
      functional groups was isolated from low-iron cultures of Acinetobacter baumannii
      ATCC 19606. The structure was elucidated by chemical degradation, fast-atom
      bombardment mass spectrometry and 1H and 13C NMR spectroscopy. Acinetobactin was
      composed of omega-N-hydroxyhistamine, threonine and 2,3-dihydroxybenzoic acid,
      the last two components forming an oxazoline ring. Acinetobactin was structurally
      related to anguibactin, a plasmid-encoded siderophore of Vibrio anguillarum. The
      only difference was that acinetobactin possessed an oxazoline ring instead of a
      thiazoline ring. Four of 12 other clinical A. baumannii strains examined produced
      acinetobactin, indicative of strain-to-strain variation in the ability to produce
      acinetobactin. In addition, a relatively small amount of acinetobactin was also
      detected in A. haemolyticus ATCC 17906.

PMID- 7802546
TI  - The Archives of Pathology and Laboratory Medicine, the American Medical
      Association, and the College of American Pathologists. A journal in transition.

PMID- 7802545
TI  - Tetrachloroethene metabolism of Dehalospirillum multivorans.
AB  - Dehalospirillum multivorans is a strictly anaerobic bacterium that is able to
      dechlorinate tetrachloroethene (perchloroethylene; PCE) via trichloroethene (TCE)
      to cis-1,2-dichloroethene (DCE) as part of its energy metabolism. The present
      communication describes some features of the dechlorination reaction in growing
      cultures, cell suspensions, and cell extracts of D. multivorans. Cell suspensions
      catalyzed the reductive dechlorination of PCE with pyruvate as electron donor at
      specific rates of up to 150 nmol (chloride released) min-1 (mg cell protein)-1
      (300 microM PCE initially, pH 7.5, 25 degrees C). The rate of dechlorination
      depended on the PCE concentration; concentrations higher than 300 microM
      inhibited dehalogenation. The temperature optimum was between 25 and 30 degrees
      C; the pH optimum at about 7.5. Dehalogenation was sensitive to potential
      alternative electron acceptors such as fumarate or sulfur; nitrate or sulfate had
      no significant effect on PCE reduction. Propyl iodide (50 microM) almost
      completely inhibited the dehalogenation of PCE in cell suspensions. Cell extracts
      mediated the dehalogenation of PCE and of TCE with reduced methyl viologen as the
      electron donor at specific rates of up to 0.5 mumol (chloride released) min-1 (mg
      protein).-1 An abiotic reductive dehalogenation could be excluded since cell
      extracts heated for 10 min at 95 degrees C were inactive. The PCE dehalogenase
      was recovered in the soluble cell fraction after ultracentrifugation. The enzyme
      was not inactivated by oxygen.

PMID- 7802544
TI  - DMSO respiration by the anaerobic rumen bacterium Wolinella succinogenes.
AB  - The anaerobic rumen bacterium Wolinella succinogenes was able to grow by
      respiration with dimethylsulphoxide (DMSO) as electron acceptor and formate or H2
      as electron donors. The growth yield amounted to 6.7 g and 6.4 g dry cells/mol
      DMSO with formate or H2 as the donors, respectively. This suggested an ATP yield
      of about 0.7 mol ATP/mol DMSO. Cell homogenates and the membrane fraction
      contained DMSO reductase activity with a high Km (43 mM) for DMSO. The electron
      transport from H2 to DMSO in the membranes was inhibited by 2-(heptyl)-4
      hydroxyquinoline N-oxide, indicating the participation of menaquinone. Formation
      of DMSO reductase activity occurred only during growth on DMSO, presence of other
      electron acceptors (fumarate, nitrate, nitrite, N2O, and sulphur) repressed the
      DMSO reductase activity. DMSO can therefore be used by W. succinogenes as an
      acceptor for phosphorylative electron transport, but other electron acceptors are
      used preferentially.

PMID- 7802547
TI  - College of American Pathologists Mycobacteriology E Proficiency Testing Survey.
      Summary of participant performance, 1979-1992.
AB  - The College of American Pathologists first offered a program of proficiency
      testing in mycobacteriology in 1969 to laboratories that offered any extent of
      diagnostic service. This program was intended to provide a mechanism for
      evaluation of methods of staining, culture, identification, and susceptibility
      testing. From 1979 to 1992, the period covered by this review, participation in
      the Mycobacteriology E Survey increased almost sixfold. On graded smears to be
      stained for detection of acid-fast bacilli, more than 85% of Extent 4 and Extent
      3 laboratories and more than 80% of Extent 2 laboratories responded correctly to
      all specimens except one. Performance on specimens that contained Mycobacterium
      tuberculosis was similar for Extent 4 and Extent 3 laboratories. For all
      specimens containing M tuberculosis, a mean of more than 90% of Extent 4 and
      Extent 3 laboratories provided a correct identification each year except 1979,
      when a mean of 83% of Extent 3 laboratories responded correctly. Only Extent 4
      laboratories were required to identify isolates other than M tuberculosis to the
      species level. For specimens that contained nontuberculous mycobacteria, the
      means of the yearly averages of correct responses for Extent 4 laboratories were
      90% or greater for M kansasii, M marinum, M avium complex, and M fortuitum
      chelonae complex and less than 85% for M bovis, M simiae, M scrofulaceum, M
      szulgai, M flavescens, M xenopi, M terrae complex, and M gastri. In general, on
      these same specimens, a slightly higher percentage of Extent 3 laboratories
      (which were required to identify only M tuberculosis to the species or complex
      level) gave correct or acceptable responses, and the performance of Extent 2
      laboratories (which were only required to report whether or not a mycobacterium
      was present) was the best of all extents. The data suggest that laboratory
      performance improved somewhat after initial experience with uncommonly
      encountered organisms. For the most part, however, performance with a given
      species changed minimally from year to year.

PMID- 7802548
TI  - DNA fingerprinting of pathogenic bacteria by fluorophore-enhanced repetitive
      sequence-based polymerase chain reaction.
AB  - Fluorophore-labeled oligonucleotide primers complementary to defined interspersed
      repetitive sequences conserved in diverse bacteria were used in the polymerase
      chain reaction to generate DNA fingerprint patterns from selected pathogenic
      bacteria. Fluorophore-enhanced, repetitive sequence-based polymerase chain
      reaction allowed discrimination between unrelated isolates of penicillin
      resistant Streptococcus pneumoniae recovered from pediatric patients and
      Mycobacterium avium cultured from patients with acquired immunodeficiency
      syndrome. Combinations of oligonucleotide primers labeled with distinct
      fluorescent dyes enabled simultaneous DNA fingerprinting and Shiga-like toxin
      gene detection in enterohemorrhagic Escherichia coli isolates. Fluorophore
      enhanced, repetitive sequence-based polymerase chain reaction was performed with
      either purified DNA or intact cells that were lysed during the polymerase chain
      reaction. Fluorophore-enhanced, repetitive sequence-based polymerase chain
      reaction successfully combines polymerase chain reaction amplification and
      fluorescent label detection for DNA fingerprinting of cultured bacterial
      pathogens.

PMID- 7802549
TI  - Serology as a valid screening test for Helicobacter pylori infection in
      asymptomatic subjects.
AB  - Serologic testing is generally accepted as a valid noninvasive screening method
      for the detection of a Helicobacter pylori infection. To validate serology as an
      appropriate screening test for H pylori infection in symptom-free subjects, a
      recent-generation enzyme-linked immunosorbent assay for the detection of H pylori
      specific IgG was performed in a large series of asymptomatic women. Blood samples
      for H pylori serology were taken from 542 apparently healthy women (aged 20 to 40
      years) during prenatal screening. In this group, 120 (22.1%) had a positive titer
      for H pylori. We observed a significantly higher overall prevalence of H pylori
      seropositivity in nonwhites (62.3%) when compared with Belgian-born whites
      (17.8%). In both groups there was a significant increase in seropositivity with
      increasing age. To investigate the correlation between a positive enzyme-linked
      immunosorbent assay and the actual presence of an active H pylori infection,
      carbon 13-labeled urea breath tests were performed in 85 seropositive and in 65
      randomly selected seronegative subjects. These breath tests were positive in 82
      (96.5%) of 85 seropositive and in none of the seronegative subjects, reflecting
      an actual presence of H pylori in the gastric mucosa of the seropositive women.
      We conclude that in our population of H pylori-seropositive subjects positive
      serologic findings correlates extremely well with an active infection with this
      bacterium. However, because all subjects who were investigated were actually
      symptom-free, it still should be determined whether these patients should undergo
      upper gastrointestinal endoscopy and/or be treated with an eradication therapy
      against H pylori. Further long-term follow-up studies will be required to answer
      this question.

PMID- 7802550
TI  - Early diagnosis of cytomegalovirus pneumonitis in lung transplant patients.
AB  - Cytomegalovirus (CMV) pneumonitis is an important cause of morbidity and
      mortality in lung transplant patients and requires timely and accurate diagnosis.
      This study compares the diagnostic utility of the evaluation of transbronchial
      biopsy by histology, immunohistochemistry, and simultaneous culture of
      bronchoalveolar lavage in a population of 13 lung transplant patients who
      underwent 78 biopsies during a period of 27 months. Our study concludes that, in
      patients clinically symptomatic for CMV pneumonitis, histology alone is
      diagnostic for the presence of the virus, whereas culture of bronchoalveolar
      lavage fluid is not as helpful. In asymptomatic patients, however,
      immunohistochemistry utilizing monoclonal antibodies to immediate-early and early
      CMV nuclear antigens may indicate development of CMV pneumonitis before
      cytopathic changes are evident.

PMID- 7802551
TI  - Localization of human immunodeficiency virus 1 RNA in thymic tissues from
      asymptomatic drug addicts.
AB  - Thymic tissue was collected from 11 human immunodeficiency virus 1 (HIV-1)
      seropositive drug users who died suddenly of drug intoxication or trauma. None of
      the 11 individuals had symptoms related to HIV-1 infection or were known to be
      seropositive for HIV-1 before death. Secondary B-cell follicles were present in
      every thymus, and Warthin-Finckeldey giant cells were noted in three cases. These
      follicles were enlarged or fragmented and appeared similar to those in lymph
      nodes excised from the same individuals. Localization of viral RNA by in situ
      hybridization demonstrated abundant virus in a follicular center cell
      distribution within hyperplastic follicles and in scattered medullary
      lymphocytes. In nine thymus glands from seronegative drug addicts and five thymus
      glands from seronegative trauma victims who were not drug addicts, secondary
      follicles were absent and no hybridization signal was present. Other than the
      presence of germinal centers associated with HIV-1 RNA, there were no histologic
      differences among the thymus glands of seropositive drug addicts, seronegative
      drug addicts, and seronegative controls without a history of drug abuse. We
      conclude that the thymus gland in early stages of infection with HIV-1 is
      characterized by induction of secondary B-cell follicular hyperplasia in
      medullary tissues, the germinal centers of which contain abundant viral RNA.

PMID- 7802552
TI  - Multiple red cell transfusions and alloimmunization. Experience with 6996
      antibodies detected in a total of 159,262 patients from 1985 to 1993.
AB  - This retrospective study of red cell antibodies covered the period from 1985 to
      1993. A three-cell antibody screen, 22% albumin enhancement, and a polyspecific
      antiglobulin reagent assay were performed. From a total of 159,262 patients in
      the data set, 6996 antibodies were detected among the sera of 4700 patients
      (2.9%). Four thousand two hundred thirty-five (60.5%) alloantibodies of potential
      clinical significance were found. These included anti-K1 (23.0%), -E (17.6%), -D
      (12.4%), -Le(a) (7.3%), -C (6.3%), -Fya (5.7%), and -c (4.4%). Cold agglutinins
      were found in 1119 positive antibody screens, 261 had warm autoantibodies, and
      554 had high-titered, low-avidity antibodies. Three hundred seven were clinically
      insignificant (eg, Sda and Bga). Five hundred seventeen were too weak to
      identify. Most patients' sera demonstrated only one antibody (69.3%), but there
      was a strong linear correlation between the total number of recorded red cell
      transfusions and the number of antibodies found (r = .976; P < .0001). There was
      a higher percentage of females with antibodies than the percentage of females in
      the total study population (59.2% versus 43.8%, P < .0001). Two hundred nine of
      554 (37.7%) high-titered, low-avidity antibodies and 349 (31.2%) of 1119 of the
      cold agglutinins accompanied or obscured clinically significant antibodies.

PMID- 7802553
TI  - Vascular lesions of the liver in sickle cell disease. A clinicopathological study
      in 26 living patients.
AB  - BACKGROUND: Hepatic lesions in sickle cell disease have been studied essentially
      in autopsy series. Previous reports on living patients are rare and concern a
      limited number of cases. The aim of the present study is to report the clinical,
      biochemical, and hepatic histological findings in 26 living patients with sickle
      cell disease and hepatobiliary disease. PATIENTS AND METHODS: Twenty-six of 510
      patients with sickle cell disease, in whom liver tissue was available for
      histological analysis, were selected. In 21 patients, biopsy was obtained during
      laparotomy for cholecystectomy; 5 patients underwent needle biopsy for
      hepatomegaly and/or liver test abnormalities. RESULTS: Twenty of the 21
      cholecystectomized patients, as well as the 5 other patients, had liver vascular
      lesions consisting of sinusoidal dilatation (23 cases), perisinusoidal fibrosis
      (19 cases), and acute ischemic necrosis (5 cases). It is of interest that the 21
      cholecystectomized patients had clinical signs of complicated cholelithiasis, and
      that 20 of them had gallbladder stones, with common bile duct lithiasis in only 1
      case. In the 25 patients without common bile duct obstruction, symptoms might
      have been due to vascular lesions, but it must also be noted that in the
      cholecystectomized patients they did not persist or recur following surgery. In
      one cirrhotic patient, marked sinusoidal lesions might have favored severe
      hepatocellular failure that led to liver transplantation. In another patient,
      fatal hepatocellular insufficiency was possibly due to ischemia. The nonvascular
      lesions that were observed, ie, chronic persistent or mildly active hepatitis (11
      cases) and cirrhosis (2 cases), were always associated with vascular lesions.
      CONCLUSION: These results suggest that in sickle cell disease: (1) hepatic
      lesions are mainly vascular; (2) these lesions can be responsible for acute
      and/or chronic ischemia that may be severe; (3) symptoms suggestive of acute
      cholecystitis and/or biliary tract obstruction might be, at least in part,
      explained by vascular lesions; and (4) biliary tract surgery indications should
      be considered more carefully.

PMID- 7802554
TI  - Discordant immunophenotype of chronic B-cell lymphoproliferative disorders in
      simultaneous specimens from bone marrow and peripheral sites.
AB  - This study consisted of 10 cases of chronic B-cell lymphoproliferative disorders
      that had simultaneous specimens obtained from both bone marrow and peripheral
      sites for flow cytometric immunophenotyping. The immunophenotyping results of
      peripheral sites from all 10 cases showed a monoclonal B-cell proliferation
      expressing monoclonal surface immunoglobulin, CD19, CD20, HLA-DR, and CD5 (except
      1 case). Eight (80%) of the 10 cases, however, demonstrated discordant
      immunophenotypes with myeloid-associated marker expression (CD13, CD11b, and/or
      CD15) found only in the bone marrow. Patients with CD13 or CD11b marker
      expression in the bone marrow followed an aggressive clinical course with
      advanced Rai's stage and a diffuse or mixed bone marrow infiltration pattern or
      disease transformation. These results indicate that discordant immunophenotypes
      of malignant cells from different body sites occur in chronic B-cell
      lymphoproliferative disorders and are not uncommon. Additionally; myeloid
      associated markers, which some investigators have described as being associated
      with an unfavorable clinical course, may be expressed only in bone marrow
      specimens in these disorders. Thus, bone marrow specimens may be preferential in
      determining myeloid-associated marker expression in chronic B-cell
      lymphoproliferative disorders.

PMID- 7802555
TI  - The neuropathology of cardiac allograft transplantation. An autopsy series of 18
      patients.
AB  - OBJECTIVE: To examine the neuropathologic findings associated with cardiac
      transplantation and to assess the role, if any, that the neuropathology had in
      the patient's death. DESIGN: Retrospective autopsy series of 18 patients.
      SETTING: Tertiary referral center with a high volume of cardiac transplantation.
      PATIENTS: Cardiac transplant patients who died and in whom a complete autopsy was
      performed. RESULTS: Eighteen patients, including 11 men and seven women,
      comprised the study group. Patients ranged in age from 27 to 59 years (mean 48
      years). Postoperative survival ranged from 1 to 1517 days (mean 334 days).
      Autopsies in 15 (83%) patients showed neuropathology; in only one patient,
      however, was cause of death attributed to these findings. The most common
      neuropathology was related to anoxia or infarction: ischemia or focal neuronal
      necrosis (n = 9), diffuse anoxic encephalopathy (n = 3), infarction (n = 6).
      Other findings included infection with Nocardia, Aspergillus, and Staphylococcus
      (n = 3) and hemorrhage (n = 3). Of the seven patients who received transplants
      for ischemic heart disease, five had evidence of cerebral ischemia or infarction.
      Systemic pathology encountered included infection in 13 patients, ischemia and/or
      infarction in 11 patients, and hemorrhage in six patients. Cause of death was
      attributed to infection in nine patients, cardiac rejection in five patients,
      disseminated intravascular coagulation/hemorrhage in three patients, and systemic
      amyloidosis in one patient. CONCLUSIONS: The most common neuropathologic findings
      are related to ischemia and infarction. Neuropathologic findings were only rarely
      the main cause of death, but they were a significant cause of morbidity in
      patients who have undergone cardiac allograft transplantation.

PMID- 7802556
TI  - The significance of signet ring cells in infiltrating lobular carcinoma of the
      breast.
AB  - To determine the prognostic significance of signet ring cells in infiltrating
      lobular carcinomas, the percentage of signet ring cells in 99 infiltrating
      lobular carcinomas was correlated with the patients' clinical outcomes (mean
      follow-up interval of 4.8 years). When the carcinomas were divided into those
      with 0%, 1-9%, and 10% or more signet ring cells, 57% (26/46) of patients with
      10% or more signet ring cells had experienced recurrences or metastases compared
      with 40% (2/5) and 31% (15/48) with 0% and 1-9%, respectively. A similar analysis
      performed with breakpoints at 20% or 30% failed to yield any statistically
      significant associations. When patients were stratified by pathologic stage,
      patients with stage I disease and 10% or more signet ring cells were more likely
      to have recurrences or metastases than those patients with stage I tumors and
      fewer than 10% signet ring cells. There was no relationship between signet ring
      cells and disease progression in stages II, III, and IV. These results indicate
      that the presence of 10% or more signet ring cells represents a poor individual
      prognostic factor in stage I infiltrating lobular carcinomas.

PMID- 7802557
TI  - Unusual mesenchymal and mixed tumors of the salivary gland. An
      immunohistochemical and flow cytometric analysis of three cases.
AB  - Histological, immunohistochemical, and flow cytometric characteristics of three
      unusual parotid gland tumors are described. The patients were adult white men
      with carcinoma ex pleomorphic adenoma, true malignant mixed tumor, and primary
      parotid gland chondrosarcoma. The carcinoma ex pleomorphic adenoma showed
      evidence of simultaneous epithelial, myoepithelial, and mesenchymal
      differentiation by immunohistochemistry. The true malignant mixed tumor exhibited
      variable positivity for two keratins, vimentin, proliferating cell nuclear
      antigen, Ki67, and p53. The chondrosarcoma initially stained for vimentin, S100,
      muscle-specific actin, proliferating cell nuclear antigen, and Ki67, but it lost
      actin expression in its first recurrence, accompanied by more extensive Ki67
      staining. DNA ploidy varied from diploid to aneuploid with intratumoral variation
      in the carcinosarcoma. S-phase fractions ranged from 2.43% to 13.9%. The findings
      underscore the diversity of tumors that may be pathogenetically related to, and
      at times derived from, pleomorphic adenoma.

PMID- 7802558
TI  - Occurrence of primary renal angiosarcoma in brothers.
AB  - Two brothers, 3 years apart in age, developed angiosarcoma of the left kidney at
      ages 52 and 69. Both rapidly developed systemic metastasis and died 6 weeks and 3
      months, respectively, after nephrectomy. No common carcinogen or hereditary or
      other etiologic factor was identified. To our knowledge these two cases bring the
      total of reported cases of renal angiosarcoma to eight, with these representing
      the only ones with a familial occurrence.

PMID- 7802559
TI  - Transitional cell carcinoma exhibiting clear cell features. A differential
      diagnosis for clear cell adenocarcinoma of the urinary tract.
AB  - We report two cases of transitional cell carcinoma of the urinary tract that
      consist of optically clear cells rich in glycogen. We propose that transitional
      cell carcinoma may exhibit a clear cell morphologic variant that should be
      distinguished from clear cell adenocarcinoma.

PMID- 7802560
TI  - Immunolocalization of E-cadherin in human head and neck cancer.
AB  - Loss of expression of the cell-cell adhesion molecule E-cadherin has been shown
      to have a potential role in the dedifferentiation and progression of many human
      malignancies. We applied immunohistochemical staining for E-cadherin to eight
      formalin-fixed, paraffin-embedded primary and matched metastatic human head and
      neck carcinomas. In tumors that contained both well-differentiated and poorly
      differentiated components, staining was notably reduced in the poorly
      differentiated cells. Staining was nearly identical or only slightly reduced in
      metastases compared to primary tumors. As found in previous reports, E-cadherin
      expression may be involved in the dedifferentiation of these tumors.

PMID- 7802561
TI  - Munchausen's syndrome and the laboratory. Self-injection of human chorionic
      gonadotropin.
AB  - A woman presented to our emergency center after self-injection of human chorionic
      gonadotropin in an attempt to gain admission to the hospital. Her initial urine
      pregnancy test (an assay for beta-hCG) was negative. Subsequent blood samples
      received from the patient the same day revealed markedly elevated beta-hCG
      levels, suggesting possible laboratory error. Although the patient's sonogram was
      negative for an intrauterine pregnancy, an ectopic pregnancy could not be ruled
      out and the patient was taken to surgery, where no evidence of pregnancy was
      found. Retrospective evaluation of the patient's medical history revealed that
      she had 30 previous surgical procedures, for which most were performed for
      alleged gynecological reasons. The authors suggest that this case of Munchausen's
      syndrome illustrates one of the more interesting solutions for a "laboratory
      error."

PMID- 7802562
TI  - Peripheral T-cell non-Hodgkin's lymphoma following treatment of nodular
      lymphocyte predominance Hodgkin's disease.
AB  - Previous reports have suggested that nodular lymphocyte predominance Hodgkin's
      disease (NLPHD) is a germinal center-derived B-cell lymphoma that is distinct
      from other types of Hodgkin's Disease. A relationship between NLPHD and
      simultaneous or subsequent development of large-cell (LC) non-Hodgkin's lymphoma
      (NHL) has been established. Both Reed-Sternberg cell variants in NLPHD and NHL
      cells in these cases express B-cell-associated antigens, and in some cases the B
      cell lineage of the NHL has been confirmed by immunoglobulin gene rearrangement
      studies. The B-cell phenotype and the indolent course of both lymphomas suggest
      histologic progression of NLPHD to B-cell NHL, rather than a de novo LCNHL
      unrelated to Hodgkin's Disease. We report a unique case of T-large-cell lymphoma
      (TLCL) following successful chemotherapy of NLPHD. A 54-year-old male was treated
      with seven cycles of mechlorethamine, vincristine, procarbazine, prednisone
      chemotherapy for NLPHD and 4 years later developed recurrent adenopathy. Lymph
      node biopsy showed a diffuse LCNHL. Frozen section immunotyping and gene
      rearrangement studies confirmed the diagnosis of TLCL. To our knowledge, this
      case represents only the second report of TLCL associated with NLPHD and is of
      significance in that: (1) it demonstrates that T-cell neoplasia can occur in the
      setting of NLPHD; (2) this case does not appear to represent histologic
      progression of NLPHD and most likely represents de novo disease that may be
      secondary to chemotherapy; and (3) the clinical course may differ from the
      favorable prognosis seen in NLPHD associated with B-cell NHL.

PMID- 7802563
TI  - Clinical pathology residency training: the need for reform.

PMID- 7802564
TI  - Coccidioides immitis presenting as a hyphal form in a ventriculoperitoneal shunt.
AB  - We report a case of meningitis in a 31-year-old man caused by Coccidioides
      immitis, where the organism was observed growing in the cerebrospinal fluid
      exclusively as hyphae. This unusual morphology was seen in fluid obtained from a
      ventriculoperitoneal shunt. Only C immitis was cultured. Its identity was
      confirmed by both DNA probes and standard culture techniques. To our knowledge
      this is the second report of C immitis taking a hyphal form in cerebrospinal
      fluid. Coccidioides immitis should be considered in the differential diagnosis
      when hyphal forms are seen in body fluids. The diagnosis can be hastened by using
      DNA probes, which enhance patient therapy and worker safety.

PMID- 7802565
TI  - ACTH-producing pituitary carcinoma presenting as the cauda equina syndrome.
AB  - A 43-year-old woman presented with incontinence, weakness, and paresthesia,
      consistent with the cauda equina syndrome, 10 years after having a pituitary
      tumor surgically removed and 4 years after excision of two "meningiomas" of the
      cervical cord. The patient was also hypertensive and had a cushingoid habitus.
      Emergent surgical decompression of the spinal cord revealed intradural metastatic
      adrenocorticotropic hormone-producing pituitary carcinoma. Pituitary carcinomas
      are rare. The majority of reported cases of adrenocorticotropic hormone-producing
      carcinoma have exhibited metastases outside the central nervous system. To our
      knowledge, this represents the first case of an adrenocorticotropic hormone
      producing pituitary carcinoma presenting with the cauda equina syndrome. A review
      of all reported cases of pituitary carcinoma indicated that central nervous
      system metastases were more common than metastases to distant sites, and patients
      with distant metastases experienced a shorter duration of disease than did those
      with central nervous system metastases.

PMID- 7802566
TI  - Pilomatricoma of the testicle. An ossifying testicular tumor with hair matrix
      differentiation.
AB  - Teratomas of the testis account for 4% of all testicular tumors. Monodermal
      variants (eg, epidermal inclusion cysts) account for less than 1% of all these
      tumors. To our knowledge, we are reporting the first case of pilomatricoma of the
      testis, a monodermal teratomatous tumor of follicular differentiation, with
      secondary heterotopic ossification. The differential diagnosis of the
      characteristic "shadow" cells is discussed, and the significant literature on
      both benign and malignant ossifying lesions of the testis is reviewed.

PMID- 7802567
TI  - Simultaneous endometrial malignant mixed mesodermal tumor and ovarian serous
      adenocarcinoma.
AB  - Although simultaneous endometrial and ovarian tumors are observed occasionally,
      rarely are the two neoplasms histologically disparate. We report a case of
      simultaneous endometrial malignant mixed mesodermal tumor and ovarian serous
      adenocarcinoma with a single right external iliac lymph node metastasis. Using
      immunohistochemical profiles, we demonstrated that the two tumors are separate
      primary neoplasms and identified the origin of the metastatic deposit as the
      mixed malignant mesodermal tumor.

PMID- 7802568
TI  - Technical and practical considerations involved in operations on patients
      weighing more than 270 kg.
AB  - Care of the patient with superobesity requires special precautions and
      appropriate equipment. Recently, we performed bariatric procedures (modified very
      long-limb Rouxen-Y gastric bypass) on patients weighing 355 kg and 377 kg. These
      procedures required preoperative preparation concerning safe means of transport
      of the patient, techniques of anesthesia and intraoperative exposure, provisions
      for postoperative recovery, and measures to assure patient comfort and hygiene
      postoperatively. In addition to specially designed bariatric procedures for the
      superobese, specialized equipment is needed to protect the health of the patient
      and the staff. All health care providers and especially acute care centers must
      have preconceived protocols to treat the superobese patient. In addition,
      specialized equipment is necessary to allow safe transport and support of these
      patients.

PMID- 7802569
TI  - Preoperative highly selective catheter localization of occult small-intestinal
      hemorrhage with methylene blue dye.
AB  - In patients with occult lower gastrointestinal bleeding, locating of the source
      of the hemorrhage can be quite difficult. While multiple diagnostic tests may
      confirm a small bowel source of bleeding, precise localization allowing a
      directed, conservative surgical resection may be problematic. We describe three
      patients each of whom presented with hemorrhage from the small intestine. The
      preoperative use of highly selective angiographic catheter placement combined
      with intraoperative methylene blue dye injection allowed us to precisely locate
      the source of hemorrhage and to resect a conservative length of small intestine.
      This technique has been successful in the three patients herein, and we believe
      that it should be included in the options available to the surgeon.

PMID- 7802570
TI  - Improved survival after intraoperative cardiac arrest in noncardiac surgical
      patients.
AB  - OBJECTIVE: To test the hypothesis that improvements in intraoperative and
      perioperative critical care are resulting in an improved outcome after
      intraoperative cardiac arrest. DESIGN: A retrospective consecutive series of
      patients who experienced an intraoperative cardiac arrest during
      noncardiothoracic surgical procedures between January 1986 and June 1994.
      SETTING: A tertiary care university-based hospital. PARTICIPANTS: Twenty-four
      consecutive patients who experienced an intraoperative arrest among 162,661
      noncardiothoracic surgical procedures during the designated period. INTERVENTION:
      Advanced cardiac life support and advanced trauma life support methods were used
      appropriately. Postarrest pharmacologic and mechanical cardiopulmonary support
      were used as needed in the setting of a surgical intensive care unit. MAIN
      OUTCOME MEASURES: Survival out of the operating room and survival to discharge.
      RESULTS: Fifteen patients (62%) were resuscitated in the operating room and taken
      to the surgical intensive care unit or recovery room. Nine patients (38%)
      survived to discharge from the hospital. Twelve arrests (50%) were primarily
      cardiac in origin. Predictors of mortality included a need for pressor or
      inotropic support (P < .001) and duration of the arrest greater than 15 minutes
      (P < .001). CONCLUSION: Survival from an intraoperative cardiac arrest in a
      noncardiothoracic surgical patient is much improved over rates in historical
      controls who experienced in-hospital and out-of-hospital cardiac arrest. Rapid
      identification and aggressive correction of mechanical and metabolic derangements
      is warranted.

PMID- 7802571
TI  - Postoperative T-tube cholangiography: is routine antibiotic prophylaxis
      necessary? A prospective, controlled study.
AB  - OBJECTIVE: To determine the value of antibiotic prophylaxis for the prevention of
      infection following postoperative T-tube cholangiography. DESIGN: A prospective,
      controlled study. SETTING: A tertiary care center. STUDY PARTICIPANTS: The role
      of antibiotic prophylaxis during postoperative T-tube cholangiography was
      prospectively evaluated in 164 patients. INTERVENTION: Sixty-two patients were
      administered antibiotic prophylaxis treatment (1 g of cephalothin sodium was
      infused intravenously 30 minutes before the procedure and 500 mg of cephalexin
      was given orally every 6 hours for 3 days after the procedure). Seventy-one
      patients were in the control group and did not receive antibiotic therapy. MAIN
      OUTCOME MEASURES: Complications and adverse reactions following postoperative T
      tube cholangiography were recorded and compared between the two groups. RESULTS:
      There was no significant difference between the groups in regard to age, sex,
      serum amylase level before T-tube cholangiography, white blood cell count, and
      liver function. The results of the bacteriologic culture specimens of the bile
      were also comparable between the groups. One patient who had received antibiotic
      therapy and one patient in the control group had fever (temperature, > 38 degrees
      C) and chills after the procedure. Two patients who had received antibiotic
      therapy and one patient in the control group had mild abdominal pain. These
      complications were treated conservatively without any event. No significant
      difference was found in the rates of complications and the success of
      postoperative T-tube cholangiography between the groups. CONCLUSION: Routine
      antibiotic prophylaxis for the prevention of infection following postoperative T
      tube cholangiography is not necessary under selected conditions.

PMID- 7802572
TI  - Surgical residents in the 1990s. Issues and concerns for men and women.
AB  - OBJECTIVE: To survey the concerns of surgical residents in New England and to
      determine whether similarities or differences exist based on gender.
      DESIGN/SETTING: A survey was distributed to all 21 surgical residency programs.
      The survey consisted of six demographic questions and 23 items, which the
      residents coded on a Likert-type scale. PARTICIPANTS: Surgical residents enrolled
      in a general surgical residency or specialty residents completing general surgery
      requirements. INTERVENTION: Distribution and completion of the survey. MAIN
      OUTCOME MEASURE: Prominent concerns among residents during training years and
      gender differences based on these concerns. RESULTS: All programs responded. A
      completed survey was returned by 501 residents (73%), 378 (75%) of whom were male
      and 123 (25%) of whom were female. On a scale of 1 to 5 (from no concern to major
      concern), the five most important issues were work hours (mean, 3.4), personal
      finances (mean, 3.1), quantity and quality of formal education (mean, 3.0 each),
      and postponement of family plans (mean, 2.9). Six items surveyed were of more
      concern to women than men; availability of role models, mentors, or both; comfort
      in expressing emotions at work; initiating and maintaining personal
      relationships; having children during residency; and postponing family plans.
      CONCLUSIONS: Three of the highest-reported concerns for the entire group are
      issues that could conceivably be controlled by surgical chairpersons and program
      directors. In contrast, only one of the six concerns that differed for men and
      women is directly program related. The remaining five issues require changes in
      societal values for these differences to dissolve.

PMID- 7802573
TI  - Postoperative course after inguinal herniorrhaphy. A case-controlled comparison
      of patients receiving workers' compensation vs patients with commercial
      insurance.
AB  - OBJECTIVE: To confirm our observation that patients with work-related hernias,
      when compared with self-employed patients, had longer recovery times and
      prolonged pain after hernia repairs, we reviewed our recent experience in a
      series of patients undergoing inguinal hernia repairs. DESIGN: The study design
      was matched retrospective case-control. Each patient receiving workers'
      compensation was age and sex matched with a control patient with commercial
      insurance whose repair was done during the same year. SETTING: All inguinal
      herniorrhaphies were performed at a single clinic by one of seven surgeons.
      PATIENTS: Twenty-two consecutive patients receiving workers' compensation and 22
      patients with commercial insurance were studied. MAIN OUTCOME MEASURES: The
      postoperative courses in 22 consecutive patients with workers' compensation were
      compared with those in 22 control patients with commercial insurance. The
      principal factors compared were indications for surgery, type of hernia, surgical
      repair performed, the duration of postoperative pain, and the number of days off
      daily work. RESULTS: The average age in both groups was 46 years. Hernias in the
      workers' compensation group were more frequently symptomatic. The duration of
      postoperative pain (mean +/- SE) was 111.0 +/- 42.2 days for patients with
      workers' compensation and 17.8 +/- 7.9 days for patients with commercial
      insurance (P < .05). The number of days off work (mean +/- SE) was 33.5 +/- 4.6
      days for patients receiving workers' compensation and 12.6 +/- 2.3 days for
      patients with commercial insurance (P < .001). CONCLUSIONS: We believe our
      results confirm the observation that type of insurance coverage influences post
      operative recovery time after inguinal herniorrhaphy. Other studies measuring a
      patient's outcome after surgical procedures such as herniorrhaphy should include
      type of insurance coverage as a factor that might affect early return to work.
      Using multivariate analysis, the only variable independently affecting the
      duration of pain after hernia repair was the type of insurance coverage (P <
      .005).

PMID- 7802576
TI  - Incidence and management of pancreatic and enteric fistulas after surgical
      management of severe necrotizing pancreatitis.
AB  - OBJECTIVE: To determine the incidence, type, and outcome of complications of
      necrotizing pancreatitis. SETTING: Major tertiary referral center (Mayo Clinic,
      Rochester, Minn). PATIENTS: Sixty-one patients seen from 1985 to 1994 who
      underwent surgical management of severe necrotizing pancreatitis and who
      developed pancreatic or gastrointestinal fistulas. MAIN OUTCOME MEASURES:
      Incidence, management, and outcome of pancreatic and gastrointestinal fistulas.
      RESULTS: Twenty-five patients (41%) developed pancreatic (14 patients) and/or
      gastrointestinal tract cutaneous (19 patients) fistulas. While three duodenal
      fistulas and one colonic fistula were recognized at the initial operation for
      pancreatic necrosectomy, the remainder developed 4 to 60 days after the initial
      operation. Spontaneous closure occurred in nine of 14 pancreatic, two of two
      gastric, two of four enteric, two of eight colonic, and four of five duodenal
      fistulas. Mortality of the group with fistulas was 24% (6/25) and was not
      different from the mortality of the patients with necrotizing pancreatitis
      without fistulas (28% [10/36]). CONCLUSIONS: Pancreatic and gastrointestinal
      tract fistulas are common complications of surgical treatment of severe
      necrotizing pancreatitis. Well-controlled gastric, pancreatic, and enteric
      fistulas have the greatest likelihood of spontaneous closure. Duodenal and
      colonic fistulas may need surgical intervention for control or repair. Mortality
      in these patients parallels the mortality for severe necrotizing pancreatitis.

PMID- 7802574
TI  - Allotransplantation of whole spleen in patients with hepatic malignant tumors or
      hemophilia A. Operative technique and preliminary results.
AB  - BACKGROUND: It has been reported that the spleen performs a vital function in the
      fight against malignant tumors. The spleen is the primary producer of tuftsin,
      which can directly or indirectly kill tumor cells or inhibit their growth. The
      spleen is also believed to produce coagulating factor VIII. Therefore,
      allotransplantation of the spleen can be used in the treatment of patients with
      malignant tumors and hemophilia A. DESIGN: Heterotopic allotransplantation of
      whole spleen was performed in six patients with advanced hepatocellular carcinoma
      and hemophilia A. An adjuvant immunotherapy with interferon alfa was
      simultaneously administered in the patients with liver cancer. SETTING: Tongji
      Hospital, Tongji Medical University, Wuhan, China. RESULTS: Among six cases of
      allografting of whole spleen, five grafts were successful; one failed because of
      torsion of the splenic hilum. Three patients with hepatocellular carcinoma
      survived 9, 11, and 5 months after transplantation. Marked shrinkage of hepatic
      tumors and reduced serum alpha-fetoprotein levels were observed in these
      patients. On 5-year follow-up, three patients with hemophilia who had undergone
      splenic allografts were alive, and two had experienced substantial clinical
      improvement. In these two patients, when the grafts were functioning well and the
      recipients were free of acute rejection or graft-vs-host reaction, the mean
      plasma factor VIII activity remained between 30% and 36%, with peak factor VIII
      activities of 53.7% and 66.6%. We also evaluate operative technique and
      posttransplantation complications. CONCLUSION: Our results strongly imply that
      the spleen is one of the primary sites of synthesis of factor VIII and that the
      spleen has an inherent ability to fight malignant diseases. Allografting of whole
      spleen may be a promising technique for the treatment of patients with
      unresectable hepatocellular carcinoma and severe hemophilia A.

PMID- 7802575
TI  - Long-term morbidity after regional isolated perfusion with melphalan for melanoma
      of the limbs. The influence of acute regional toxic reactions.
AB  - OBJECTIVE: To determine the influence of acute regional toxic reactions on the
      incidence and characteristics of long-term morbidity after regional isolated
      perfusion with melphalan. DESIGN: Retrospective study. SETTING: The Amsterdam and
      Rotterdam perfusion centers, the Netherlands. PATIENTS: All patients with
      melanoma who were treated between 1978 and 1990 and had a minimum follow-up of 1
      year after perfusion (n = 367). INTERVENTION: Fifty-four patients (15%) had
      perfusion of the upper limb, 313 (85%) had perfusion of the lower limb, and 164
      patients (45%) underwent regional lymph node dissection at the time of perfusion.
      MAIN OUTCOME MEASURE: Incidence and characteristics of morbidity 1 year after
      perfusion and the influence of acute regional toxic reactions on long-term
      morbidity. RESULTS: One hundred sixty patients (44%) showed some degree of
      objective or subjective morbidity; most (104 [28%]) had lymphedema. Other long
      term morbidity consisted of muscle atrophy or fibrosis (42 [11%]), limb
      malfunction (55 [15%]), neuropathy (13 [4%]), pain (28 [8%]), and recurrent
      infection (11 [3%]). Miscellaneous complications were seen in 14 patients (4%).
      Seventy-one patients (19%) had more than one complication. Acute regional toxic
      reactions had a statistically significant effect on the incidence of long-term
      morbidity (P < .01). Moderate to severe acute regional toxic reactions were
      strongly linked to the occurrence of muscle atrophy or fibrosis (P < .001) and
      limb malfunction (P < .001). Regional lymph node dissection was statistically
      significantly related to lymphedema (P = .05). CONCLUSION: Improvement of the
      perfusion technique should be pursued in an effort to reduce acute regional toxic
      reactions, and thereby long-term morbidity, without compromising the therapeutic
      effect.

PMID- 7802577
TI  - The effect of endotoxin on intestinal mucosal permeability to bacteria in vitro.
AB  - OBJECTIVE: To examine the role of the intestinal mucosa in bacterial
      translocation, in vitro bacterial passage across ileal mucosal segments mounted
      in Ussing chambers were studied in control and endotoxin (lipopolysaccharide)
      treated rats. DESIGN: Experimental study. MATERIALS AND METHODS: Three groups of
      rats were studied. The experimental group received an intraperitoneal injection
      of lipopolysaccharide, while controls received an equivalent volume of saline
      solution; a third group received no treatment. Twenty-four hours later, all
      groups underwent laparotomy and organ culture to assess bacterial translocation.
      At the same time, a segment of mucosa from the terminal ileum of each animal was
      mounted in a Ussing chamber, and the transmucosal passage of labeled Escherichia
      coli from the luminal to serosal surface was assessed by results of serial
      cultures. RESULTS: In vivo bacterial translocation occurred in 100% of the
      lipopolysaccharide-treated animals, significantly higher than the incidence seen
      in controls (25%; P < .05). In vitro passage of labeled E coli across ileal
      mucosa in the Ussing chamber occurred in 78% of lipopolysaccharide-treated
      animals, while in controls transmucosal passage was seen in only 14% (P < .05).
      Histologic examination of mucosa from both groups using light and transmission
      electron microscopy demonstrated no structural differences between groups.
      CONCLUSIONS: Increased permeability to bacteria at the mucosal level contributes
      to the bacterial translocation seen in endotoxemia.

PMID- 7802578
TI  - Transmural gut oxygen gradients in shocked rats resuscitated with heparan.
AB  - OBJECTIVES: To develop a reproducible model to measure transmural gut tissue PO2,
      to determine the gradient from serosa to mucosa during normovolemia and
      hypovolemia, and to determine the effect of resuscitation with heparan sulfate
      (danaparoid sodium) on this gradient. DESIGN: Fluorescent tissue oxygen sensors
      were placed onto serosal and mucosal surfaces of rat colon. Hemorrhagic shock was
      induced using a fixed pressure (mean arterial pressure, 40 mm Hg) model and
      resuscitated with either saline solution or heparan. RESULTS: Control animals had
      stable mean (+/- SD) serosal and mucosal tissue oxygen tensions (PO2) of 64 +/- 4
      and 10 +/- 2 mm Hg, respectively. In shocked animals, baseline serosal PO2
      decreased to 37 +/- 2 mm Hg at a mean (+/- SD) of 19 +/- 7 minutes after the
      initiation of hemorrhage. Mucosal values decreased to a minimum of 4 +/- 2 mm Hg
      at 45 +/- 15 minutes after the initiation of hemorrhage. Serosal PO2 returned to
      baseline during resuscitation in both control and heparan-resuscitated animals.
      Mucosal PO2 did not return to baseline in the shock/no heparan group. In the
      heparan-resuscitated animals, however, mucosal PO2 increased above baseline (13
      +/- 3 mm Hg at 3 hours after completion of hemorrhage). CONCLUSIONS: A transmural
      gradient of PO2 exists across the colon with mucosal PO2 far lower than serosal
      PO2. Both serosal and mucosal PO2 decrease during hypovolemia. During
      hypovolemia, the PO2 of the entire gut wall is in a range in which phagocytic
      killing is impaired by hypoxia. Heparan improved mucosal PO2 and it may restore
      and/or protect gut function by oxygen-related mechanisms.

PMID- 7802579
TI  - Relation of epidermal growth factor receptor and estrogen receptor-independent
      pS2 protein to the malignant transformation of mucinous cystic neoplasms of the
      pancreas.
AB  - OBJECTIVE: To evaluate the role of epidermal growth factor receptor (EGF-R) and
      pS2 protein in the evolution of malignancy in mucinous cystic tumors of the
      pancreas. BACKGROUND: Mucinous cystic tumors of the pancreas include
      histologically benign but premalignant mucinous cystic neoplasms and mucinous
      cystadenocarcinoma. The molecular events leading to transformation from a benign
      to a malignant mucinous tumor are not known. Overexpression of EGF-R and
      detection of an estrogen-induced protein (pS2) has been demonstrated in ductal
      adenocarcinomas of the pancreas, but these factors have not been evaluated in
      mucinous cystic tumors. DESIGN: Twenty-six mucinous tumors were examined for EGF
      R, pS2 protein, and estrogen and progesterone receptors. RESULTS: Eight (61.2%)
      of 13 malignant tumors exhibited increased expression of EGF-R, whereas EGF-R was
      not detected in any of the 13 benign tumors (P = .002). The pS2 protein was
      detected in nine of 11 malignant and 11 of 11 benign tumors (P = .480). Estrogen
      and progesterone receptors were not detected in the epithelium of either tumor
      type. The median survival time of the patients with EGF-R-negative tumors was
      29.0 months compared with 14.5 months for those with EGF-R-positive tumors, but
      this difference did not reach significance owing to the small population size.
      CONCLUSIONS: Overexpression of EGF-R in mucinous cystic tumors, as in ductal
      adenocarcinomas, may be an important feature associated with malignancy and may
      have prognostic significance. Failure to detect EGF-R in histologically benign
      epithelium suggests that the upregulation of EGF-R may be important in the
      evolution of aggressive behavior. The expression of pS2 protein appears to be
      independent of estrogen and may play a role in the proliferative activity of
      mucinous tumors. However, pS2 expression is not a feature associated exclusively
      with malignancy.

PMID- 7802580
TI  - Detection of human papillomavirus DNA in colorectal adenomas.
AB  - OBJECTIVE: To assess the presence of different types of human papillomavirus
      (HPV) DNA in colorectal adenomas. DESIGN: The extracted DNA of 109 formalin
      fixed, paraffin-embedded tissue sections of colorectal adenomas were analyzed by
      polymerase chain reaction and Southern blot hybridization. The correlations of
      HPV types 6, 11, 16, 18, and 33 DNA with the histological patterns of adenomas
      were also analyzed. RESULTS: Human papillomavirus DNA was detected in 28% of the
      adenomas. There were eight (21%) of 38 in tubular adenomas, 13 (33%) of 40 in
      tubulovillous adenomas, and 10 (32%) of 31 in villous adenomas. All HPV-6/11
      positive cases were tubular or tubulovillous adenomas. However, most HPV-16
      infections (8/12) were seen in villous adenomas. Human papillomavirus-positive
      adenomas included three (8%) of 38 that showed mild dysplasia, 10 (25%) of 40
      that showed moderate dysplasia, and 18 (58%) of 31 that showed severe dysplasia.
      CONCLUSION: The association of the histological type with HPV-16 and the
      association of the grade of epithelial dysplasia with HPV DNA were highly
      significant. These associations support the adenoma-carcinoma hypothesis. In
      addition, the results suggest that HPV infection may be an important factor for
      the development of colorectal neoplasia.

PMID- 7802581
TI  - Comparison of APACHE II and III scoring systems for mortality prediction in
      critical surgical illness.
AB  - OBJECTIVE: To determine whether the Acute Physiology and Chronic Health
      Evaluation III (APACHE III), an updated version of APACHE II that contains a
      larger number of postoperative patients in the normative database, offers better
      prediction in critical surgical illness. DESIGN: Prospective cohort study.
      SETTING: Surgical intensive care unit of an urban, tertiary-care university
      hospital. PARTICIPANTS: Eight hundred forty-four consecutive patients in the
      surgical intensive care unit. Overall scores were determined, as well as scores
      for survivor, nonsurvivor, trauma, nontrauma, postoperative, and nonoperative
      patient subgroups. MAIN OUTCOME MEASURES: Survival to hospital discharge, and
      survival compared with published normative APACHE II and III databases. RESULTS:
      Mean age was 65.1 +/- 0.5 years. Overall mortality was 7.0% in the surgical
      intensive care unit and 9.1% in the hospital. The relationship between APACHE II
      and APACHE III scores for individual patients was linear and correlated
      significantly (P < .0001) (range of correlation coefficients, .72 to .86) overall
      and in all subgroups. Both scoring systems overestimated our mortality, but
      estimations made by APACHE III were significantly (P < .01) higher overall and in
      all subgroups. CONCLUSIONS: In institutions or groups of patients where APACHE II
      underestimates mortality, APACHE III may be corrective. However, the differences
      are subtle and may be difficult to detect in smaller studies.

PMID- 7802582
TI  - Comparative evaluation of educational methods in surgical resident education.
AB  - OBJECTIVE: To determine the influence of study methods on American Board of
      Surgery (ABS) examination performance. DESIGN: Performance on ABS examinations by
      and faculty evaluations of 54 categorical surgical residents from 1976 to 1992
      were correlated with the residents' use of commonly available educational methods
      (textbooks, Selected Readings in General Surgery, grand rounds, preceptor
      guidance, clinical surgery review courses, surgical science review courses,
      Surgical Education and Self-Assessment Program [SESAP], and continuing medical
      education lectures) in early, late, and after residency. SETTING: An average
      sized midwestern US university surgical residency. RESULTS: Residents who
      consistently scored above the 33rd percentile on ABS examinations had used texts
      early, Selected Readings later, and SESAP after residency more frequently than
      those with ABS In-Training Examination scores in the lower one third. Selected
      Readings and clinical review courses were associated with significant increases
      in ABS percentile scores when used in late or after residency and, along with
      SESAP, were used when residents improved their low ABS In-Training Examination
      scores. CONCLUSIONS: Independent study methods are the most effective pathway to
      successful ABS examination performance. Formal surgical review courses may help
      improve the ABS examination scores of residents at a higher risk of failure.

PMID- 7802583
TI  - Acral lentiginous melanoma.
AB  - OBJECTIVE: To analyze whether the histologic subtype acral lentiginous melanoma
      confers independent prognostic significance. DESIGN: Case series retrospective
      review. SETTING: Academic surgical practice. PATIENTS OR OTHER PARTICIPANTS:
      Fifty-six patients with histologically confirmed acral lentiginous melanoma
      identified from patients with malignant melanoma consecutively treated by the
      faculty of the Department of Surgical Oncology at the University of Illinois at
      Chicago. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Lymph node
      metastases, disease-free survival, and overall concurrent or subsequent survival.
      RESULTS: The average age of our patients with acral lentiginous melanoma was 61.1
      years. Thirty-four (61%) were white, and the remaining 22 (39%) were African
      American, Hispanic, or Asian. Thirty (54%) were male and 26 (46%) were female.
      The primary tumor occurred on the lower extremity in 46 (82%) of the cases and on
      the upper extremity in the remaining 10 (18%). Twenty-four primary tumors (43%)
      were greater than 4.00 mm thick. Analyzed by means of a logistic regression
      model, the rate of lymph node metastases did not significantly differ among
      patients with acral lentiginous melanoma, superficial spreading melanoma, and
      nodular malignant melanoma. Furthermore, when corrected for tumor thickness,
      disease-free and overall survival were the same for the three histologic groups.
      Multifactorial analysis identified only thickness as a prognostic variable for
      disease-free survival and overall survival. CONCLUSIONS: Despite the greater age,
      diverse ethnic background, and distinctive tumor characteristics of our patients
      with acral lentiginous melanoma, this histologic subtype does not, in itself,
      affect the outcome of these patients.

PMID- 7802584
TI  - K-ras status does not predict successful hepatic resection of colorectal cancer
      metastasis.
AB  - OBJECTIVE: To establish whether specific K-ras alterations are predictive of less
      aggressive tumor behavior and subsequently those patients who are most likely to
      benefit from resection of hepatic metastases from colorectal carcinoma. DESIGN:
      Evaluation of long-term survivors of hepatic resection for metastases of
      colorectal carcinoma (median survival, 85 months). RESULTS: DNA, extracted from
      26 paraffin-embedded hepatic metastases from 19 patients, was analyzed using
      single-strand conformation polymorphism and direct sequence analysis of codons 12
      and 13 of the K-ras gene. Seven of 19 patients were found to harbor K-ras
      mutations. A similar frequency and spectrum of K-ras mutational events was
      detected in 14 patients with short-term survival following pathologic diagnosis
      of hepatic metastasis. CONCLUSIONS: Neither the presence of a K-ras mutational
      event nor the precise nucleotide change are predictive of less aggressive tumor
      behavior, and genetic alterations at this locus alone cannot be used to select
      patients undergoing resection of hepatic metastases from colorectal carcinoma.

PMID- 7802585
TI  - Anti-neutrophil antibody attenuates the severity of acute lung injury in rats
      with experimental acute pancreatitis.
AB  - OBJECTIVE: To examine the role of activated neutrophils in microvascular injury
      after severe acute pancreatitis. We used the polyclonal anti-rat neutrophil
      antibody (PoAb) to deplete peripheral neutrophil counts and the anti-rat
      monoclonal antibody (MoAb) CD18 to block neutrophil adherence functions. DESIGN:
      Prospective, controlled trial. SETTING: Laboratory. PARTICIPANTS: Anesthetized
      male Wistar breeder rats, in which necrotizing pancreatitis was induced by
      injecting necrotizing agents into the pancreatic duct. INTERVENTIONS: Treatment
      groups received an infusion of PoAb, 8 mL/kg, before induction of pancreatitis or
      MoAb CD18, 2 mg/kg, after induction of pancreatitis. Control animals received 2
      mL of rabbit serum or 1 mL of saline solution. MAIN OUTCOME MEASURES: Survival
      rate, white blood cell count, levels of serum amylase and lipase, myeloperoxidase
      activity in the lung, lipid peroxide levels in the pancreas, and results of
      histological studies. RESULTS: The survival rate of rats treated either with PoAb
      before or MoAb CD18 after induction of sepsis improved significantly (P < .01).
      Histologically and according to the levels of neutrophil myeloperoxidase in their
      lungs, rats treated with the antibodies 24 hours after inducing pancreatitis
      improved significantly (P < .05). Moreover, the serum lipase concentrations and
      lipid peroxide levels in the pancreas of these rats decreased significantly (P <
      .05). CONCLUSIONS: Both the depletion of peripheral neutrophils by PoAb and
      blocking of neutrophil adherence functions by MoAb CD18 may help to prevent acute
      lung injury caused by severe acute pancreatitis in this model.

PMID- 7802586
TI  - Prevention of seromas in mastectomy wounds. The effect of shoulder
      immobilization.
AB  - OBJECTIVE: To determine if postoperative shoulder immobilization decreases the
      incidence of postmastectomy seromas. DESIGN AND SETTING: A prospective randomized
      trial of three surgeons' experiences at a community hospital. PATIENTS: Thirty
      eight patients who underwent modified radical mastectomy from March 1991 through
      February 1993. MAIN OUTCOME MEASURES: Incidence of postmastectomy seromas and
      time required for patients to gain 110 degrees of shoulder abduction after
      surgery. RESULTS: Thirteen (72%) of 18 wounds in the maximum range of motion
      cohort developed seromas (72%) compared with one (6%) of 17 in the minimum range
      of motion cohort (P = .0005). The average time required for the patients with
      maximum range of motion to gain 110 degrees of shoulder abduction was 2.6 weeks,
      whereas the patients with minimum range of motion required an average of 5.0
      weeks (P = .0127). CONCLUSION: Postmastectomy shoulder immobilization
      significantly decreases the incidence of wound seromas. Although this protocol
      resulted in a delay in return to normal shoulder mobility, no patients sustained
      long-term musculoskeletal dysfunction.

PMID- 7802587
TI  - 1,N2-cyclic deoxyguanosine adducts and guanine adducts of 2-haloacroleins.
      Isolation, characterization, isomerization and stability.
AB  - The reaction of the mutagenic 2-haloacroleins, 2-fluoroacrolein, -2
      chloroacrolein and 2-bromoacrolein, with nucleosides and 5'-mononucleotides was
      studied. We found two different regioisomers of 1,N2-cyclic deoxyguanosine
      adducts of 2-chloroacrolein and 2-bromoacrolein: type A, the 6-hydroxy, 7
      haloadduct in which the OH-substituent is vicinal to the N2-atom of the guanine
      moiety and type B, the 8-hydroxy, 7-haloadduct in which the OH-group is adjacent
      to the N1-atom of the guanine moiety. The major adducts were the trans pairs of
      diastereomers of type A and type B in which the 6,7-substituents as well as the
      7,8-substituents are in the energetically favoured diaxial position of the newly
      formed tetrahydropyrimidine ring. In the case of the type A regioisomers, the cis
      pairs of diastereomers (traces with chloroacrolein and about 4% with
      bromoacrolein) were also found in which the halosubstituent probably takes the
      equatorial position. Due to the anomeric effect, the OH-group takes the axial
      position in both regioisomers. No cis isomers of the type B regioisomers could be
      isolated. Acid hydrolysis of the deoxyguanosine adducts released deoxyribose, and
      the respective guanine adducts were isolated and characterized. Besides the
      vicinal halo, hydroxy adducts, trace amounts of the corresponding dihydroxy
      adducts were formed by hydrolysis of the chlorine or bromine substituents. The
      dihydroxy compounds possess the same structures and conformations in the newly
      formed tetrahydropyrimidine ring as do the halo, hydroxy adducts. Under our
      conditions no adducts other than those with deoxyguanosine and guanine could be
      identified.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7802588
TI  - Pharmacokinetics of the oximes HI 6 and HLo 7 in dogs after i.m. injection with
      newly developed dry/wet autoinjectors.
AB  - The rapid onset of cholinergic crisis after intoxication with highly toxic
      organophosphorus compounds calls for pre-clinical administration of effective
      antidotes as early as possible. For this purpose, i.m. administration of the
      antidotes by autoinjectors is desired to allow early treatment also in the
      absence of a physician. Besides atropine, oximes with broad antidotal spectrum
      are considered valuable adjuncts that should be included in antidotal mixtures.
      To circumvent the problem of limited stability of the new-generation oximes,
      dry/wet autoinjectors were developed in which the unstable solid is dissolved by
      a diluent in an adjacent chamber upon activation of the device. In this study the
      tolerance, bioavailability and pharmacokinetics of 500 mg HI 6 [1-(((4
      (aminocarbonyl) pyridinio)methoxy) methyl)-2-((hydroxyimino)methyl) pyridinium
      dichloride monohydrate] or 200 mg HLo 7 [1-(((4-(aminocarbonyl)
      pyridinio)methoxy)methyl)-2,4- bis((hydroxyimino)methyl)pyridinium
      dimethanesulfonate] in combination with 2 mg atropine sulfate versus atropine
      alone, delivered by two dry/wet autoinjector types, were investigated in eight
      male beagle dogs (16 kg) in a complete cross-over design. The dogs tolerated the
      six injections with 3-week intervals without any symptoms of discomfort.
      Nonetheless, CPK activity increased, peaking at 6 h after injection. In contrast
      to atropine which merely led to a marginal increase, HI 6 plus atropine increased
      the baseline CPK activity about 10-fold, and HLo 7 plus atropine about 20-fold,
      regardless of the injector type. The HI 6 autoinjectors from Astra Tech were from
      an irregular production batch which did not deliver the declared HI 6 dose. The
      HLo 7 autoinjectors from Astra Tech and both Binaject autoinjectors from STI
      functioned well: the bioavailability was complete with tmax values of about 25
      min as observed after conventional i.m. injection. The absorption half-time was
      about 8 min, elimination t1/2 about 50 min, and Vapp 0.26 l/kg. The urinary
      recovery of unchanged oximes was 70-80%, the renal clearance being the same as
      for inulin. Unexpectedly, hematocrit and hemoglobin content of blood decreased by
      about 15% within 2 h and reached pre-treatment values after 6-24 h. This decrease
      was observed with all three drug treatments and could not be accounted for by
      blood loss (< 4%), thus pointing to an atropine effect. In conclusion, the newly
      developed dry/wet autoinjectors appear suitable for the administration of
      atropine and an oxime stored in solid form.

PMID- 7802589
TI  - Computer assisted recognition and quantitation of the effects of airborne
      chemicals acting at different areas of the respiratory tract in mice.
AB  - The pattern and timing of a normal breath in unanesthetized mice was analyzed
      from measurement of inspiratory and expiratory airflows (VI and VE). Airflow was
      measured via a differential pressure transducer, attached to a pneumotachograph,
      which itself was attached to a body plethysmograph into which a mouse was placed.
      The analog voltage from the differential pressure transducer was digitized and
      stored for analysis on a microcomputer. Criteria were developed to classify each
      breath as normal (N) or belonging into one of seven abnormal categories. The
      abnormal categories were arrived at by computer analysis, recognizing specific
      modifications of the normal pattern into patterns of: sensory irritation of the
      upper respiratory tract (S), airflow limitation within the conducting airways of
      the lungs (A) or pulmonary irritation at the alveolar level (P). Combinations of
      these effects, i.e., S+A, P+A, P+S and P+S+A were also recognized. Computer
      analysis of each breath also permitted quantitative evaluation of the degree of
      S, A or P abnormalities. To induce each type of effect we used inhalation
      exposures to 2-chlorobenzylchloride, carbamylcholine or propranolol. We propose
      that this approach will permit rapid evaluation of the possible effects of
      airborne chemicals at three levels of the respiratory tract, with the
      classification of the type of effect easily obtained in an objective way using
      well defined criteria, followed by quantitation of the degree of each effect.

PMID- 7802590
TI  - Identification of four metabolites of 3-(phenylamino)alanine, a constituent in L
      tryptophan products implicated in eosinophilia-myalgia syndrome, in rats.
AB  - 3-(Phenylamino)alanine (PAA), a contaminant found in L-tryptophan tablets, has
      been discussed as a possible cause of eosinophilia-myalgia syndrome (EMS). We
      administered PAA (100 mg/kg) by gastric gavage to Wistar rats to determine its
      distribution and metabolism. We developed a purification procedure, using Bond
      Elut SCX cartridges followed by high performance liquid chromatography (HPLC) in
      order to determine levels of PAA. The level of PAA in blood was 4.22
      micrograms/ml at 5 h and urinary excretion was 21.7 micrograms for 5 h and 84.6
      micrograms between 5 and 24 h. The amount of PAA in the contents of the large
      intestine at 5 h was 0.76 microgram, indicating poor transfer of PAA to the large
      intestine. However, the highest concentration of PAA was 12.3 micrograms/g in the
      brain, indicating the passage of PAA through the blood-brain barrier. In addition
      to detecting PAA in the blood and organs, we also detected four metabolites of
      PAA in urine. We used gas chromatography mass spectrometry to identify PAA in rat
      liver, as well as N-(hydroxyphenyl)glycine, N-phenylglycine, 3-(pheylamino)lactic
      acid, and 3-(hydroxyphenylamino)-lactic acid in rat urine. These results suggest
      that the degradation pathway of PAA is similar to that of phenylalanine.

PMID- 7802593
TI  - Pulmonary elimination of methyl tertiary-butyl ether after intraperitoneal
      administration in mice.
AB  - The pulmonary elimination after intraperitoneal administration at three different
      doses (50, 100, and 500 mg/kg) of methyl tertiary-butyl ether (MTBE) was studied
      using mice. There were two exponential curves with an initial rapid decrease of
      the elimination ratio followed by a slow decrease at the doses of 100 mg/kg and
      500 mg/kg. The calculated half-lives of the two elimination curves obtained by
      the least squares method were approximately 45 min and 80 min. The pulmonary
      elimination ratios at the three different doses were from 23.2% to 69.0%. Most of
      the excreted MTBE was eliminated within 3 h. It is suggested in this paper that
      MTBE in exhaled air can be used as a biological exposure index for the exposure
      assessment of MTBE.

PMID- 7802592
TI  - Acute effects of methylmercury on hepatic and renal glutathione metabolisms in
      mice.
AB  - Because of its high affinity to the sulfhydryl group, the in vivo fate of
      methylmercury (MeHg) is closely related to the glutathione (GSH) metabolism.
      Here, to examine the possible effects of MeHg on the GSH metabolism, C57BL female
      mice were challenged by this heavy metal at a marginal dose level to induce
      slight renal dysfunction. Liver and blood GSH levels decreased by 16% and 20%,
      respectively, 24 h after MeHg (160 mumol/kg) administration, whereas kidney and
      plasma levels drastically increased. The GSH half-lives obtained using L
      buthionine-(S,R)-sulfoximine were shortened by 17% in the liver, but lengthened
      by 28% in the kidney. The accelerated secretion of GSH from the liver and/or
      blood cells might have caused increased plasma levels of the tripeptide, which in
      turn could increase the supply of the constituent amino acids for GSH synthesis
      to the kidney. Furthermore, renal gamma-glutamylcysteine synthetase activity, a
      rate-determining enzyme in GSH biosynthesis, was found to be enhanced in the MeHg
      treated group. The marked increase in the renal GSH levels induced by MeHg could
      be due to the increased synthesis and the decreased efflux of the tripeptide in
      this tissue. The MeHg-induced alterations of GSH metabolism described here might
      reflect one of the defense mechanisms of bioorganisms against the challenge by
      MeHg.

PMID- 7802591
TI  - Effects of clofibric and beclobric acid in rat and monkey hepatocyte primary
      culture: influence on peroxisomal and mitochondrial beta-oxidation and the
      activity of catalase, glutathione S-transferase and glutathione peroxidase.
AB  - The effect of hypolipidaemic compounds on peroxisomal fatty acid beta-oxidation
      and on peroxisome morphology in the liver differs widely between rodent and
      primate species. We studied the relative importance of peroxisomal and
      mitochondrial beta-oxidation of palmitate in primary cultures of hepatocytes
      isolated from rat and monkey liver in the absence or presence of clofibric acid
      or beclobric acid. It was demonstrated that it is possible to differentiate
      between peroxisomal and mitochondrial beta-oxidation activities in intact cells.
      Overall beta-oxidation of palmitate was ca. 30% higher in rat hepatocytes than in
      monkey liver cells. In both monkey and rat cell cultures the mitochondrial
      component was over 90% of the total palmitate beta-oxidation. In rat hepatocyte
      culture clofibric acid and beclobric acid caused a 5- to 8-fold stimulation of
      peroxisomal beta-oxidation, while in monkey cells this activity was not
      significantly increased. However, in cells derived from both species
      mitochondrial palmitate beta-oxidation was increased (rat 2.5-fold; monkey 1.5
      fold). These results indicate that the species differences in the increase in
      peroxisomal fatty acid oxidation are not a result of an inability to metabolize
      fatty acids in rat liver cell mitochondria. A comparison of the activity of
      enzymes involved in the detoxification of hydrogen peroxide showed that catalase
      and glutathione-S-transferase activity is 2.9-fold higher in monkey hepatocytes
      than in rat liver cells, while glutathione peroxidase activity was 1.6-fold
      higher in rat cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7802594
TI  - Biliary excretion of exogenous cadmium and manganese in Long-Evans Cinnamon (LEC)
      rats characterized by an inherently gross amount of copper-metallothionein in the
      liver.
AB  - Long-Evans Cinnamon (LEC) rats are characterized by the sudden onset of hepatitis
      around 4 months after birth and the gross accumulation of hepatic copper (Cu)
      accompanied by metallothionein (MT). The biliary excretion of manganese (Mn) and
      cadmium (Cd) injected intravenously was studied in 3-month-old LEC rats without
      signs of hepatitis. Injected Mn was excreted into the bile in LEC and Fischer
      rats used for comparison. However, increased biliary excretion of Cd was found
      not in the LEC rat but in the Fischer rat. Excretion of horseradish peroxidase
      (HRP) injected along with the metal mixture was significantly lower in the LEC
      group than in the Fischer group. Our results suggest that Mn excretion is not
      related to the existence of a gross amount of Cu-MT. Reduced excretion of Cd may
      be partly due to binding to Cu-MT in the liver. Decreased excretion of HRP
      implies the existence of an inherent defect in the bile excretion route for endo-
      and exogenous substances.

PMID- 7802595
TI  - Styrene-7,8-oxide in blood of workers exposed to styrene.
AB  - A field study was carried out on 13 workers exposed to styrene vapors at time
      weighted average concentrations between 10 and 73 ppm. The reactive intermediate
      styrene-7,8-oxide was determined in blood samples using a direct gas
      chromatographic method. Styrene-7,8-oxide concentrations were in the range
      between 0.9 and 4.1 micrograms/l blood. Linear correlations were found between
      styrene-7,8-oxide in blood and styrene in ambient air and blood. For an exposure
      concentration of 20 ppm styrene (German MAK value) a steady-state level of about
      1 microgram styrene-7,8-oxide/l blood was calculated.

PMID- 7802596
TI  - Cobalt bioavailability from hard metal particles. Further evidence that cobalt
      alone is not responsible for the toxicity of hard metal particles.
AB  - Hard metal is an alloy of tungsten carbide (WC) in a matrix of cobalt metal (Co).
      The inhalation of hard metal dust can cause an alveolitis which may progress to
      interstitial fibrosis. This study was undertaken to compare, both in vivo and in
      vitro, the bioavailability of cobalt metal when mixed or not with WC and to
      assess whether this factor had any influence on the cellular toxicity of hard
      metal particles. In vivo, non-toxic doses of cobalt metal were administered
      intratracheally in the rat, alone (Co, 0.03 mg/100 g) or mixed with tungsten
      carbide (WC-Co, 0.5 mg/100 g containing 6.3% of cobalt metal particles).
      Sequential measurements of cobalt in the lung and in urine demonstrated that the
      retention time of the metal in the lung was longer in Co- than in WC-Co-treated
      animals. In vitro, the cellular cobalt uptake was higher when the metal was
      presented to the macrophages as WC-Co. However, there was no relationship between
      the cellular uptake of cobalt and the occurrence of toxicity, since the
      intracellular concentration of cobalt associated with the occurrence of a
      cytotoxic effect of WC-Co particles was insufficient to exert the same effect
      when resulting from exposure to Co alone. This clearly indicates that increased
      bioavailability of cobalt is not the mechanism by which hard metal particles
      exhibit their cellular toxicity. These observations confirm and extend our
      previous findings supporting the view that cobalt is not the only component
      responsible for the toxicity of hard metal particles which should be considered
      as a specific toxic entity.

PMID- 7802598
TI  - [Allergic pneumonia. Pathogenesis of summer hypersensitivity pneumonitis].

PMID- 7802597
TI  - Effects of deltamethrin on catecholamine secretion of bovine chromaffin cells.
AB  - The effects of the pyrethroid deltamethrin (D) on catecholamine secretion of
      cultured bovine chromaffin cells were investigated in vitro using high
      performance liquid chromatography (HPLC). Spontaneous release of catecholamines
      was increased by 10 microM and 100 microM D. This increase could partially be
      prevented by the simultaneous use of 2 microM tetrodotoxin (TTX), which reduced
      the increase by 10 microM D of catecholamine secretion by 90% and that of 100
      microM D by 50%. TTX 2 microM alone did not alter the spontaneous release in
      comparison to controls. Medullary chromaffin cells consist of two cell groups,
      one secreting mainly epinephrine (E), the other norepinephrine (NE). The ratio
      between the spontaneously secreted catecholamines E and NE was increased after
      treatment with D, indicating a dominant effect on E secreting cells.

PMID- 7802599
TI  - [Study of peripheral neutrophil functions of patients with Wegener's
      granulomatosis].
AB  - Recently, the detection of anti-neutrophil cytoplasmic antibodies (ANCA) has
      gained worldwide acceptance as an important additional diagnostic tool of
      Wegener's granulomatosis (WG). A possible pathogenic role of ANCA has been
      suggested by the finding that the addition of purified IgG-ANCA to healthy
      neutrophils in vitro causes activation of these cells. But, investigation on
      neutrophil functions of patients with WG has been rare. To clarify this point,
      peripheral neutrophil functions (adherence, chemiluminescence and chemotaxis) of
      patients with active WG were examined. Adherence, chemiluminescence and
      chemotaxis of patients with WG were significantly suppressed when compared with
      control subjects. The effects of ANCA positive serum on neutrophil
      chemiluminescence were also examined. ANCA positive serum did not affect
      neutrophil chemiluminescence. These results indicate that the mechanism of WG is
      not simply due to neutrophil activation by ANCA.

PMID- 7802600
TI  - [Usefulness of inhaled steroids in steroid-dependent intractable asthma-
      equivalent dose of oral steroid to inhaled steroid].
AB  - Twenty-four steroid-dependent intractable asthmatics were treated with oral
      prednisolone (PSL) (basic dose) + additional PSL and oral PSL (basic dose) +
      inhaled beclomethasone (BDP) alternately, to assess the clinical symptoms in each
      administration period. Equivalent doses of PSL to BDP were calculated. 1. Peak
      expiratory flow rate (PEF) during additional administration of BDP was markedly
      higher both in the morning and at night compared with that during additional
      administration of BDP was markedly higher both in the morning and at night
      compared with that during additional administration of PSL (p < 0.01 and p < 0.05
      respectively). 2. The relation between additional doses of either PSL or BDP and
      attack scores was analysed in regression to obtain a dose equivalence line. 3.
      BDP 400 micrograms was equivalent to PSL 7.04 mg on average. 4. The equivalent
      dose of PSL to BDP tended to be lower in cases where the period of dependency on
      oral steroids was longer, the basic dose was larger, or the asthma was more
      severe. These data indicate that the application of inhaled steroids may be
      useful in the therapeutic management of steroid-dependent intractable asthmatics.

PMID- 7802601
TI  - [Serum pyridoxal concentration in children during theophylline therapy for
      bronchial asthma].
AB  - This study was designed to investigate the effect of sustained-release
      theophylline therapy on serum pyridoxal concentration in children with bronchial
      asthma. Forty-two children with bronchial asthma were divided into two groups
      according to duration of theophylline administration: The 22 children in group A
      had been treated with theophylline for less than 4 weeks, whereas the 20 children
      in group B had been treated for more than 5 weeks. The results obtained from this
      study were as follows: 1) The serum pyridoxal concentration in group B was
      significantly lower than that those in group A (p < 0.01). 2) The serum pyridoxal
      concentration was not significantly correlated with the serum theophylline
      concentration. These findings suggest that long-term theophylline therapy can
      depress vitamin B6 status in children with bronchial asthma. Theophylline-induced
      seizure may be caused by the possible decreased in gamma-aminobutyric acid
      concentration in the brain as a result of decrease in gamma-aminobutyric acid
      concentration in the brain as a result of decrease in vitamin B6 status, even if
      the serum theophylline concentrations are within the therapeutic range.

PMID- 7802602
TI  - [Clinical characterization of allergic patients sensitized to Chamaecyparis
      obtusa--using AlaSTAT system].
AB  - Clinical characterization of patients with allergy to Chamaecyparis obtusa
      (Cypress) pollen and their specific IgE antibody was investigated by using
      AlaSTAT assay, a new method for measurement of antigen-specific IgE antibody.
      Positive rate of antigen-specific antibody in patients with allergic pollinosis
      was 83.5% for Japanese cedar pollen and 80.0% for Chamaecyparis obtusa pollen.
      76.4% of patients were sensitized both to Japanese cedar and Chamaecyparis obtusa
      pollen, however, 7.9% were sensitized only to the latter. As for clinical
      symptoms, duration of attack was short and severity was mild or moderate in the
      patients sensitized only to Chamaecyparis obtusa pollen. Patients who visited
      hospital in April, in that Chamaecyparis obtusa pollen disseminated in the air
      predominantly, showed significant elevation in AlaSTAT scores compared with
      patients who visited in February and March (p < 0.05).

PMID- 7802603
TI  - [Interleukin-5-induced generation of superoxide by eosinophils in asthma].
AB  - Superoxide generation was assessed in highly purified eosinophils (> 99.0% pure)
      with a flow cytometer. Eosinophils from patients with asthma were collected by
      centrifugation of leukocytes on Percoll density gradients, followed by negative
      immunoselection with anti-CD16 monoclonal antibodies. For comparison, highly
      purified neutrophils (< 99.5% pure) were collected by a similar method with anti
      CD9 monoclonal antibodies. After incubation with a fluorescent probe, the cells
      were stimulated with various concentrations of PAF, PMA or various cytokines.
      Both eosinophils and neutrophils generated superoxide dose-dependently in
      response to PAF and PMA. Eosinophils generated superoxide in response to IL-3 and
      IL-5 (maximum concentration was 50 ng/ml), but neutrophils did not. IL-5-induced
      superoxide generation was lower in the presence of IL-5 antibodies. After
      stimulation with PMA, superoxide generation was significantly higher in
      neutrophils than in eosinophils (p < 0.05). There were no significant differences
      in PAF-induced or GM-CSF-induced superoxide generation between eosinophils and
      neutrophils. After stimulation with the optimal concentration of IL-5 or PMA,
      eosinophils with a lower density generated significantly more superoxide than
      those with a higher density.

PMID- 7802604
TI  - [Inhibitory effect of TGF-beta 1 on cytokine-enhanced eosinophil survival].
AB  - TGF-beta 1 has many biological activities in various cell types and is regarded
      as a multifunctioning regulator of cell growth. We studied the effect of TGF-beta
      1 on cytokine-enhanced eosinophil survival in vitro. Eosinophils were purified
      from patients with mild atopic dermatitis by Percoll density gradient
      centrifugation and the CD16 negative selection/immunomagnetic beads technique.
      Eosinophil purity was greater than 95%. The purified eosinophils were incubated
      in the presence of eosinophil-activating cytokines (IL-5, IL-3, GM-CSF, IFN
      gamma) with and without TGF-beta 1 for 3 days. Eosinophil viability was
      determined by staining the cells with fluorescein diacetate and propidium iodide.
      Without cytokine, most eosinophils died by day 3 in culture, but human
      recombinant IL-5, IL-3, GM-CSF, and IFN-gamma enhanced eosinophil survival in a
      dose-dependent manner. To test the effect of TGF-beta 1 on enhanced eosinophil
      survival, eosinophils were cultured with activating cytokine and TGF-beta 1. TGF
      beta 1 inhibited eosinophil survival in a dose-dependent manner. The inhibitory
      effects of TGF-beta 1 on IL-5 enhanced survival was partially reversed by high
      concentrations of IL-5 and was completely neutralized with anti-TGF-beta
      antibody. Moreover, the apoptosis of eosinophils induced by TGF-beta 1 was
      determined with the assay of DNA fragmentation on agarose gel electrophoresis. It
      is possible that TGF-beta 1 activates the pathway of apoptosis. The results
      suggest that TGF-beta 1 may play a crucial role in the regulation of allergic
      inflammation.

PMID- 7802605
TI  - [Immediate hypersensitive reactions to the ingestion of egg white and IgE binding
      to the egg white components].
AB  - IgE is considered to be involved in immediate hypersensitive reactions (IHR)
      following egg ingestion. IgE antibody levels to egg-white (EW) antigens in the
      IHR-positive group (n = 19, mean age +/- SD = 5.2 +/- 4.5 yr) were higher than
      those in the IHR-negative group (n = 13, mean of age +/- SD = 3.6 +/- 2.2 yr).
      However, even in the IHR-negative group, some patients showed high IgE to EW.
      RAST inhibition tests with heat-treated (100 degrees C, 5, 10, and 30 min) egg
      white antigens were performed on 13 serum samples from subjects with IHR and 9
      serum samples from subjects without IHR. Heat treatment decreased the IgE-binding
      activity of egg white and it was speculated that IgE from IHR-negative subjects
      bound to relatively heat-unstable sites of egg-white antigens. Furthermore, we
      selected IHR-negative subjects (n = 8, mean of age +/- SD = 3.0 +/- 1.7 yr) with
      higher IgE antibody levels than the lowest limit of IgE to EW of the IHR-positive
      group and compared IgE to ovomucoid (OM), ovalbumin (OA), conalbumin (CA), and
      lysozyme (Ly) between these IHR-negative and positive groups. IgE-binding
      activities to egg-white components, including OA, CA, and Ly but not OM, were
      significantly decreased with heat treatment. The IHR-negative group showed
      significantly lower IgE to OM (untreated, 5, 10, 30 min treatment) and 5 min
      treated OA alone than the IHR-positive group, while no difference was found in
      IgE to other components between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7802606
TI  - [Effect of Sei-hai-to on ion transport in airway epithelial cells].
AB  - The effect of Sei-hai-to on ion transport in airway epithelial cells and its
      mechanism of action were investigated. Measurement of short-circuit current (Isc)
      using cultured epithelial cells from canine tracheal mucosa under short-circuit
      conditions showed that Isc was dose-dependently increased by the submucosal
      administration of Sei-hai-to. The response of Isc to this drug was not affected
      by pretreatment the cells with amiloride, but abolished by furosemide, or Cl-free
      condition. These results suggest that Sei-hai-to stimulates Cl ion transport
      selectively and may affect the subsequent movement of water across the airway
      mucosa to the lumen.

PMID- 7802607
TI  - [Age-related changes of B-cell immune function in patients with subacute myelo
      optico-neuropathy (SMON)].
AB  - Several kinds of immunological abnormalities have been found more frequently in
      patients with subacute myelo-optico-neuropathy (SMON). To investigate whether the
      B-cell immune system is implicated in aging in patients with SMON, we examined
      serum levels of immunoglobulin including IgG, IgM, and IgA, and the number of
      CD20+ cells (B lymphocytes) and CD20+ CD23+ cells (activated B lymphocytes) using
      flow cytometry, and compared them with those in age-matched controls. We also
      investigated whether the number of HLA-DR+ cells was correlated with those of
      CD20+ cells, CD20+ CD23+ cells, or HLA-DR+CD3+ cells (activated T lymphocytes) in
      patients with SMON. Serum levels of IgG, IgM and IgA were decreased with aging
      both in the patients with SMON and in the controls, and no significant difference
      was found between the two groups. Although the patients with SMON tended to show
      higher levels of CD20+ and CD20+ CD23+ cells than the age-matched controls, there
      were no significant differences between the two groups. The number of HLA-DR+
      cells was correlated not with that of CD20+ cells or CD20+ CD23+ cells, but with
      that of HLA-DR+CD3+ cells. In patients with SMON, it is likely that the B-cell
      immune system is mainly implicated in the effect of aging, but it is unlikely
      that other factors than aging are associated with the B-cell immune system. The
      increase in the number of HLA-DR+ cells associated with aging in patients with
      SMON reflects the increase in the number of activated T lymphocytes, and is not
      correlated with the changes of B lymphocytes.

PMID- 7802608
TI  - Temporal distribution of endogenous retinoids in the embryonic mouse mandible.
AB  - Retinoids play an important part in embryonic pattern formation. They are
      necessary for normal differentiation of odontogenic tissues and, in excess,
      disrupt the pattern of tooth formation. Excess retinoids produce supernumerary
      buds of the dental lamina in the diastema region of the mouse embryonic mandible
      where teeth do not normally form. This effect is coincident with an increase in
      epithelial proliferation and an alteration in epidermal growth factor mRNA
      expression (a gene product necessary for tooth formation). It was found by high
      performance liquid chromatography that endogenous retinoids are present in the
      developing murine mandible and that concentrations of some retinoids reach a peak
      at the time of the initiation of odontogenesis (dental lamina formation).

PMID- 7802609
TI  - Elastase release from gingival crevicular and peripheral neutrophils in
      periodontitis and health.
AB  - The activity of elastase increases significantly in the gingival sulcus during
      inflammation. The release of this enzyme from crevicular and peripheral
      polymorphonuclear leucocytes (PMNs) was studied in seven patients with
      gingivitis, six with adult periodontitis, seven with rapidly progressive
      periodontitis and in nine healthy subjects. Peripheral PMNs were isolated from
      blood and crevicular PMNs from gingival washings. After preincubation with
      cytochalasin B, the same numbers of crevicular and peripheral cells were
      incubated either in phosphate-buffered saline (spontaneous release) or in the
      same buffer containing formyl methionyl-leucyl-phenyl-alanine (stimulated
      release). Elastase activity was measured in the supernatant by a fluorimetric
      technique. The results confirm that compared to peripheral PMNs, crevicular cells
      show a higher spontaneous release of elastase and a lower stimulated release. The
      activity of elastase released either spontaneously or after stimulation of
      crevicular cells was significantly lower in the controls as compared with cells
      obtained from patients with gingivitis or periodontitis. Crevicular PMNs
      collected from patients with deeper pockets appear to release larger amounts of
      elastase than those from controls.

PMID- 7802610
TI  - The effects of mandibular hypofunction on the development of the mandibular disc
      in the rabbit.
AB  - The effect of a reduced functional dentition on the development of the mandibular
      disc in young rabbits was studied by measuring cell proliferation within the disc
      following tooth extraction. Maxillary and mandibular incisor teeth were extracted
      from 18 animals at 5 weeks of age. At 12 weeks the rabbits received 0.25 mg/kg
      vincristine sulphate. Groups of three animals were killed 1.5, 3, 6, 12, 24 and
      48 h after the injection of vincristine and the mitotic rate determined across
      the anterior, intermediate and posterior bands of the disc. Eighteen age- and sex
      matched control rabbits with intact dentitions were treated in parallel. In the
      absence of incisor teeth, reflex gnawing and incising failed to develop,
      resulting in altered jaw movements and muscle force requirements. The mitotic
      rate in the anterior band was reduced significantly (p = 0.0117); rates for the
      intermediate and posterior bands were not significantly affected. There was an
      associated reduction in alveolar bone mass and deformation of the developing
      craniomandibular complex. As the lateral pterygoid inserts into the anterior band
      of the mandibular disc, it is proposed that altered activity within this muscle,
      combined with a modified loading of the joints, both secondary to incisor
      removal, resulted in a reduced mitotic rate in the anterior band of the
      developing mandibular disc.

PMID- 7802611
TI  - Adsorption of [3H]-lipoteichoic acid to hydroxyapatite and its effect on crystal
      growth.
AB  - 3H-labelled lipoteichoic acid was isolated from Lactobacillus casei cells
      cultured in the presence of [2-3H]-glycerol. The adsorption characteristics of
      both native and deacylated [3H]-lipoteichoic acid on to hydroxyapatite crystals
      were determined in 2.0 mM CaCl2, 50 mM Hepes, pH 7.2. The maximum numbers of
      adsorption sites per unit surface area were 80 +/- 3 and 49 +/- 2 nmol/m2 for
      native and deacylated lipoteichoic acid, respectively. At low concentrations,
      which were previously found to stimulate hydroxyapatite growth in a
      supersaturated solution (1.0 mM CaCl2, 7.5 mM KH2PO4, 50 mM Hepes, pH 7.2),
      lipoteichoic acid appeared for a large part adsorbed to the crystals, while
      crystal growth was delayed when there was an excess of unbound lipoteichoic acid
      in solution. These results suggest that lipoteichoic acid released from plaque
      bacteria may have dual effects both on the precipitation of calcium phosphate in
      dental plaque and on the remineralization of lesions in the underlying hard
      tissues.

PMID- 7802612
TI  - Effect of storage media on subsequent water loss and regain by human and bovine
      dentine and on mechanical properties of human dentine in vitro.
AB  - This study was designed to determine whether storage media and time affect any
      changes in water loss with dehydration of dentine. The effect of storage of
      prepared bars was also compared with storage of whole teeth. Prepared bovine
      dentine bars were stored for 3 days or 12 weeks in deionized water, phosphate
      buffered saline or neutral-buffered formalin and whole teeth were stored in
      neutral-buffered formalin for 12 weeks before the preparation of dentine bars.
      Specimens were removed from storage and weight loss with dehydration, determined
      gravimetrically, was equated directly to water loss. Tensile and three-point bend
      tests were made on human dentine bars that had been stored in deionized water or
      neutral-buffered formalin for 3 days. Results were subjected to analysis of
      variance and Duncan's new multiple-range test. Weight loss by evaporation from
      dentine at 22.3 degrees C and 53.2% relative humidity was rapid and non-linear,
      reaching 5.05 +/- 0.55% for bovine dentine compared with 3.33 +/- 0.63% for human
      dentine after 7 days. Water loss with dehydration was not affected by 3-day
      storage of specimens in different media or by 12-week storage of whole teeth, but
      was affected when prepared specimens were stored for 12 weeks. Different storage
      media had no significant effect (p > 0.05) on the strength or toughness of human
      dentine. Water loss in human dentine was associated with shrinkage of specimens,
      but these dimensional changes were fully recovered with rehydration. Storage of
      teeth in neutral-buffered formalin followed by minimal storage time for prepared
      specimens is recommended to minimize changes in dentine after extraction.

PMID- 7802614
TI  - Variation in enamel thickness and cusp area within human maxillary molars and its
      bearing on scaling techniques used for studies of enamel thickness between
      species.
AB  - Thirty-nine unworn maxillary molars (M1 = 18, M2 = 12, M3 = 9), representing 37
      individuals of a Slavic population, were sectioned through the mesial cusps in a
      plane perpendicular to the cervical margin of the crown. Whether the range of
      variation in enamel cross-sectional area between individuals corresponds to the
      range of variation found between teeth within a species was investigated. Total
      tooth crown area, as determined by planimetry, was used as a scaling factor on
      the basis that a biologically meaningful scaling procedure should take into
      account both enamel thickness and total tooth crown area, rather than the size of
      the dentine-enamel junction. Uni- and multivariate statistics revealed that the
      enamel cross-sectional area of second and third molars is absolutely and
      relatively larger than it is in first upper molars and that it scales close to
      isometry with tooth crown area. Conversely, first maxillary molars, with their
      relatively and absolutely thinner enamel, exhibit positive allometry between
      enamel and tooth crown area. These patterns were retained even when differences
      in overall tooth size were adjusted for. Hence, the notion that there exists a
      'species-specific' amount of enamel over the tooth crown must be reconsidered,
      and one should refrain from pooling different tooth types for taxonomic purposes.
      At least two scaling factors are needed to describe human maxillary molars alone.
      However, this increase in enamel cross-sectional area from anterior to posterior
      is not unexpected if one bears in mind that posterior teeth occupy a more
      advantageous position relative to the chewing muscles.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7802613
TI  - 1 alpha,25-dihydroxyvitamin D3 stimulation of osteopontin expression in rat
      clonal dental pulp cells.
AB  - Osteopontin (OPN) is a major phosphorylated non-collagenous protein isolated from
      bone. Rat clonal dental-pulp cell lines RPC-C2A and RDP4-1 produce and secrete
      OPN as a principal phosphoprotein. 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3]
      is a potent calcitropic hormone which regulates calcified tissue metabolism
      including the synthesis of extracellular matrix proteins. The effects of
      1,25(OH)2D3 on the expression of OPN mRNA and the synthesis of OPN protein by
      pulp cells in vitro were investigated. In RPC-C2A cells, 1,25(OH)2D3 markedly
      stimulated synthesis of both [32PO4]- and [35S]-methionine-labelled OPN.
      Phosphorylated OPN synthesis increased dose-dependently and showed a maximum
      level at 48 h after addition of 10(-11)-10(-7) M 1,25(OH)2D3. Similar stimulation
      was also observed in RDP4-1 cells. Northern hybridization analysis revealed that
      1,25(OH)2D3 greatly increased the level of OPN mRNA in both pulp cell lines.
      Examination of the time course of the effects of 1,25(OH)2D3 on the level of OPN
      mRNA in RPC-C2A cells by dot-blot analysis showed that stimulation was detectable
      at 24 h and reached a maximum at 48 h after exposure to 10(-7)M 1,25(OH)2D3.
      These findings indicate that 1,25(OH)2D3 stimulates the production of dental-pulp
      OPN by a mechanism that involves de novo synthesis and transcriptional control.

PMID- 7802615
TI  - The effects of food consistency on jaw movement and posterior temporalis and
      inferior orbicularis oris muscle activities during chewing in children.
AB  - The possible effects of food consistency on the number of chews and the lapse of
      time in a chewing sequence, the jaw-movement pattern and velocity, and jaw and
      lip muscle activity during chewing were investigated. Fifteen healthy children
      with good occlusion were selected. First, each subject freely chewed hard (HJ)
      and soft (SJ) types of jelly without specifying the chewing side. The number of
      chews and elapsed time in a masticatory sequence (from the start of chewing to
      the completion of the final swallow) were measured. Second, the subjects
      performed right- and left-sided chewing of the same food. The electromyograms
      (EMG) of posterior temporalis (PT) and inferior orbicularis oris (OI) muscles on
      the right and left sides and associated jaw movement records were sampled. The HJ
      was chewed more times and with a longer time until finally swallowed (p < or =
      0.0007) than the SJ. The HJ chewing also showed broader masticatory loops (p < or
      = 0.0199) in the frontal view and higher peak activities (p < or = 0.0007) for
      the PT muscle. The closing phase was longer when chewing the HJ than SJ, but the
      opening and intercuspal phases remained stable. More lateral excursion of the jaw
      was seen when chewing the HJ, but the jaw-movement trajectories in the sagittal
      and vertical directions were not affected by the change in consistency of the
      food. The jaw-closing velocities for the HJ chews were significantly slower (p <
      or = 0.0351) than those for the SJ chews in three directions. The HJ chews also
      revealed a longer duration between the onset of EMG burst for the PT muscle and
      the beginning of the centric occlusion (p < or = 0.0146). The OI muscle showed
      increased activity in accord with jaw opening, and consistent reciprocal cyclic
      activity with the PT muscle in terms of temporal associations (r > or = 0.5250; p
      < or = 0.0495). The OI muscle started to burst at a later part of the intercuspal
      phase, and frequently showed secondary activity in the jaw-closing and
      intercuspal phases. The peak activity for the ipsilateral OI muscle was
      significantly higher (p < or = 0.0106) than that for the contralateral OI muscle
      for both the HJ and SJ. The OI muscle activity, however, did not differ between
      the hard and soft jellies.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7802616
TI  - The effectiveness of bone char in the defluoridation of water in relation to its
      crystallinity, carbon content and dissolution pattern.
AB  - The procedure for charring bone has been found to influence the nature of its
      mineral phase, and also affects the defluoridation capacity of the char. The aim
      of this study was to examine the efficiency of defluoridation by char produced
      from various parts of bones and charred for various lengths of time at various
      temperatures, relating the preparation of the char to its X-ray diffraction
      pattern, its content of pyrophosphate and its capacity for defluoridation. Bone
      was charred for 1 and 4 h at 400 degrees C and 30 min, 4 h and 48 h at 550
      degrees C. Batches of the chars were suspended in amounts of 0.25 g in 100 ml of
      distilled water containing 0.53 mmol/l fluoride for up to 6 days under gentle
      agitation. At intervals, the pH and concentrations of fluoride, calcium and
      phosphate in the water were determined and the degree of saturation with respect
      to the calcium phosphate salts calculated. The charring procedure reduced the
      organic content of the bone from the 44-26% in intact bone to 3.4% in bone
      charred at 400 degrees C and to almost zero when charred at 550 degrees C for 48
      h. When charred at 400 degrees C for up to 4 h the X-ray diffraction pattern of
      the bone showed a poorly crystallized apatite similar to that of untreated bone.
      Heating for 48 h or more at 550 degrees C led to considerably sharper apatite
      reflections, indicative of a well-crystallized salt.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7802617
TI  - Cholesterol in the distal portions of differentiating and fully differentiated
      rat odontoblasts observed by freeze-fracture.
AB  - Freeze-fracture replicas of rat molar tooth germs in conjunction with the 3-beta
      hydroxysterol marker filipin were used to study the distribution of cholesterol
      in the distal portions of odontoblast plasma membrane. Filipin-sterol
      deformations (interactions) appeared as clusters interspersed with deformation
      free regions on the distal plasma membrane of early differentiating odontoblasts.
      In fully differentiated odontoblasts, the whole distal membrane, including the
      process, was occupied by packed deformations with no free regions. It seems that
      early developing odontoblasts are poorer in cholesterol than the fully
      differentiated cells. As the content and/or distribution of 3-beta-hydroxysterols
      (cholesterol) is known to influence membrane fluidity, the low cholesterol
      content of early differentiating odontoblasts might be related to the fluidity
      required for the budding off of matrix vesicles.

PMID- 7802618
TI  - [Sex differences in the structure of the normal porcine myocardial wall].
AB  - The myocardium of 20 young sows, 20 young boars, 10 old boars and 10 old sows was
      studied histometrically. Significant sex-depending differences in the structure
      of the normal cardiac wall could be observed. In first line--exactly as in man-
      the diffusely distributed intramyocardial connective tissue is significantly
      higher in adult female subjects than in male ones. Later on, it changes and the
      amount of intramyocardial connective tissue is reduced in older sows. An
      interaction is suggested between the content of intramyocardial connective tissue
      and the estrogen level.

PMID- 7802619
TI  - [The peripartum disease complex of the sow in industrial swine breeds. 1.
      Peripartum course of bacteriuria of sows with vaginal-vulvar discharge in a
      modern swine breeding facility].
AB  - In an industrial pig production unit ten sows were selected at random. All the
      sows had puerperal disease in their anamnesis and all of them revealed at the
      time of selection--during their late pregnancy--Urinary Tract Infection (UT)I and
      vaginal-vulvar discharge (VD). Mid-stream early morning urine samples were
      collected during four days ante partum and during four days post partum. The
      samples were semiquantitatively examined for E. coli and gram positive cocci.
      Three sows showed ante partum non significant bacteriuria which turned into
      significant bacteriuria post partum. The majority of the reminding sows revealed
      a significant bacteriuria during the whole period of examination.

PMID- 7802620
TI  - [Detection of verotoxin-producing E. coli in field isolates from domestic and
      agricultural animals in Sachsen-Anhalt].
AB  - A report is given on the detection of verotoxin-producing E. coli (VTEC) strains
      from field isolates of healthy or ill cattle (n = 141), pigs (n = 306), sheep (n
      = 15), cats (n = 29) and dogs (n = 25) in the region of the new federal land
      Sachsen-Anhalt. 5% of the strains isolated from cattle, 32% from pigs, 20% from
      sheep, 4% from dogs and 0% from cats have shown VTEC. The E. coli-strains were
      checked for the presence of other factors of virulence, too. A good correlation
      (82%) was found between the colonization factor F107 and SLT 2/2v-containing
      strains from pigs in the region of Sachsen-Anhalt, too. Enterohemolysin was not
      found in SLT 2/2v-positive strains. 91% of the VTEC, isolated from pigs, produced
      alpha-Hemolysin. The correlation of SLT-containing strains and the production of
      enterohemolysin was confirmed for ruminants, only. Plasmidprofilings of VTEC from
      pigs showed mainly a 60 MDa or a 68 MDa plasmid or both, too. The occurrence of
      heat labile (LT) and in some cases of heat stable (ST) toxin was also checked, to
      differentiate the VTEC-strains from the enterotoxigenic E. coli strains (ETEC).
      These investigations showed, that VTEC produce SLT almost without exception.
      Correlations and conclusions on the pathogenicity for humans are discussed.

PMID- 7802621
TI  - [The "waiting period" for follow-up administration of bovine colostrum to newborn
      lambs].
AB  - Extent and duration of the permeability of the small intestine of newborn lambs
      for intact proteins from cow's colostrum was analyzed in five groups of animals.
      Cow's colostrum in quantities of 200 ml/kg birth weight, was offered in 3-hr
      intervals for 24 hrs, beginning either immediately after birth or after fasting,
      for 12 and 24 hrs respectively. In two groups each either 5% glucose solution or
      saline was offered to the fasting animals. The following results were obtained:
      1. All lambs fed immediately after birth drank eagerly. The intake in all fasting
      groups dropped between 12 and 24 hrs of the feeding period. 2. While the duration
      of the permeation of the small intestine for intact proteins remained unaffected
      by the various regimens, fasting with or without supplementation decreased the
      maxima. 3. The decrease in protein permeation was class-depending as demonstrated
      by the lower levels of bovine IgM in the sera of fasting lambs. 4. The
      permeability of the small intestine for proteins was substantially reduced by 5%
      glucose. The difference between fasting lambs or lambs with saline substitution
      was minimal. 5. All lambs fed immediately after birth survived. The losses in the
      other groups amounted to 29% after 12 hrs of starving, 33% after 24 hrs of
      starving, 30% after starving with glucose supplementation and 50% after saline
      solution. 6. The surviving animals showed no differences in weight gain.

PMID- 7802622
TI  - [The circadian rhythm of African ostriches (Struthio camelus) in captivity].
AB  - One hundred and twenty ostriches, kept as domestic animals on a farm in Israel
      were observed. Three behaviour categories were recorded: standing/walking,
      sitting/lying and eating/drinking. The animals spent more than 60% of the day
      standing and walking; activities with a non-life preserving function. Before we
      begin with the husbandry of ostriches in central Europe the behaviour needs of
      the animals must be determined. Only then can we assess whether the welfare of
      the animals is compatible with the method of animal husbandry we imagine for
      central Europe.

PMID- 7802623
TI  - [The problem of a high content of vitamin A in the liver of calves, cattle, sheep
      and swine for the consumer. Amount of accumulation and mechanism of teratogenic
      effect (review article)].
AB  - Cases of hypervitaminosis A in men--especially in pregnant women, with
      development of malformations--are reported. The existence of withdrawal times to
      slaughter after the application of vitamin-A-containing preparations with a
      content of 10,000 to 10(6) international units and more is described. The content
      of vitamin A in the liver of monogastric animals is closely related to that in
      the feed. In ruminants about 40 to 70% of the vitamin A of the feed is decomposed
      by the microorganisms in the forestomachs. The amount of vitamin A stored in the
      liver after a therapeutic application is dependent of the initial content. The
      velocity of the depletion of the stores at a carotene- and vitamin-A-poor feeding
      is described. In ruminants and pigs in the account of the properties of the
      placenta no embryotoxicity of a therapeutic dose of vitamin A is to be expected.
      The mechanism of the teratogenesis by vitamin A in mice is described.

PMID- 7802624
TI  - [Inheritance of notched ears in Highland cattle].
AB  - The present study describes an anomaly of the pinna of the ear and its
      distribution in Highland Cattle. The investigation is based on a questionnaire
      survey in farms in Bavaria keeping robust breeds and on registering data in 15
      selected farms. In the year 1991, there were registered 548 Highland stud book
      cows in 108 farms. In four herds animals of the breed Highland Cattle were
      observed which showed crop ears. Always both ears were affected and this ear
      defect could be already observed in newborn calves. Crop ears appeared in very
      different forms. In some cases only small changes of the external ear could be
      recognized, in more severe cases, grooves in the external ear could be found and
      in the most severe case, the external ear was totally deformed and drastically
      reduced in size. In one herd, 45 animals out of the progeny of 46 of one affected
      breeding bull showed crop ears. The pedigrees indicated that this defect of the
      ear pinna is inherited and a single autosomal gene with nearly additive
      (incomplete dominant) action may be involved. Homozygote recessive animals are
      free from crop ears, animals homozygote for the mutated allele carry totally
      deformed external ears and heterozygote animals do not show as severe forms of
      crop ears as homozygote ones.

PMID- 7802625
TI  - Strand exchange through a DNA-protein complex requires a DNA helicase.
AB  - The phage T4 uvsX and gene 32 proteins are capable of mediating homologous strand
      exchange, a central reaction in general genetic recombination, in vitro using
      naked DNA substrates. However, strand exchange is blocked by a sequence specific
      DNA-protein complex. Since protein-complexed substrates must be employed in vivo,
      this suggests that another factor(s) is required for strand exchange with protein
      complexed DNAs. We show here that a DNA helicase, the T4 dda protein, allows the
      phage recombination machinery to drive branch migration through a RNA polymerase
      promoter complex. This is the first observation of in vitro strand exchange using
      protein-bound substrates. These results suggest that a DNA helicase is a
      necessary component of the "protein machine" that mediates recombination in vivo.

PMID- 7802626
TI  - Identification of functional domains in AMPD1 by mutational analysis.
AB  - AMP deaminase (AMPD) is a complex allosteric enzyme encoded by a multigene family
      in higher eukaryotes. The amino terminus of each AMPD gene is unique, while the
      mild and carboxy termini have been highly conserved among all the AMPD genes.
      Mutational analyses of the AMPD1 gene demonstrate that the catalytic site and a
      regulatory site, likely an ATP binding site, are located in the highly conserved
      carboxy terminus. Deletion mutants and a normal splice variant of AMPD1
      demonstrate that the amino terminus has a profound influence on catalytic
      activity of AMPD and by inference from prior studies this region also influences
      binding of AMPD1 to myosin. Results of these studies suggest a regulatory model
      in which alternative splicing in the amino terminal region of AMPD1 generates
      isoforms of AMPD that exhibit differential sensitivity to effector molecules such
      as ATP.

PMID- 7802627
TI  - Essential role of polyamines in restoration of DNA synthesis after UV radiation
      and expression of UV resistance in Cockayne syndrome cells.
AB  - Activity of ornithine decarboxylase (ODC) in Cockayne syndrome (CS) cells which
      were characterized by a delay of the recovery of DNA synthesis after 254 nm
      ultraviolet light (UV) radiation was extremely inhibited by UV, followed by a
      progressive decrease of putrescine. When putrescine was added in the cultures, CS
      cells showed a rapid recovery in DNA synthesis and also an expression of UV
      resistance as seen in normal cells. Thus, ODC induction system of CS cells is
      highly sensitive to UV. Considering current hot spots in DNA repair, our results
      probably reflect a defect of preferentially rapid repair in ODC gene of CS cells.

PMID- 7802628
TI  - Localization of rhodopsin by immunofluorescence microscope in Chlamydomonas
      reinhardtii.
AB  - Using anti-rhodopsin antibody, an immunofluorescence method was established in
      Chlamydomonas reinhardtii in order to locate rhodopsin in the cell. The method
      showed that rhodopsin is located in the membrane near (or around) the pigmented
      eyespot in green algae. In synchronized cells, the location of rhodopsin changes
      regularly during the cell cycle. The fluorescence (F) spot moves from the
      anterior region toward the posterior region of the chloroplast (cp) in the light
      period. Following cell division, the F spots reappear in each daughter cell
      whether the daughter cells are released from the mother cell wall or not. The F
      spot is located opposite the site of the last cleavage furrow whether the cell
      has divided once, twice, or three times. The F spot moves back toward the
      anterior region from the equatorial plane after division in the dark period. In
      white algae eyespot-deficient mutants, rhodopsin does not depend on the presence
      of the eyespot. The results further showed that rhodopsin resides in the
      plasmalemma.

PMID- 7802629
TI  - Synaptotagmin is an inositol polyphosphate binding protein: isolation and
      characterization as an Ins 1,3,4,5-P4 binding protein.
AB  - We isolated a binding protein for inositol 1,3,4,5-tetrakisphosphate (InsP4) from
      detergent-solubilized mouse cerebellar membrane fractions by sequential column
      chromatographies. Partial amino acid sequencing of the purified sample revealed
      that the protein is essentially identical to rat synaptotagmin II, an integral
      membrane protein of synaptic vesicles. Immunoprecipitation experiment of
      [3H]InsP4 binding activity of the purified protein using polyclonal antibody
      against the C2A domain of rat synaptotagmin II also revealed that mouse
      synaptotagmin II is the InsP4 binding protein (IP4BP). Scatchard analysis of
      InsP4 binding to the IP4BP/synaptotagmin indicates a single binding site with a
      Kd of 30 nM. The present finding that InsP4 binds strongly to synaptotagmin II
      suggests an important role for inositol polyphosphates in the regulation of
      neurotransmitter release.

PMID- 7802630
TI  - Differential effects of protein phosphatase 2A on distinguishable intracellular
      signals initiated by v-Src and mediated by HaRas.
AB  - v-Src activates gene expression mediated by serum response elements (SREs) and
      TPA response elements (TREs). v-Src-induced SRE- and TRE-mediated gene
      expressions are both dependent upon HaRas. Protein phosphatase 2A (PP2A) is a
      serine/threonine phosphatase that has been implicated in v-Src-initiated signals.
      We report here that expression of the catalytic subunit of PP2A upregulates v-Src
      and v-HaRas-induced TRE-mediated gene expression, whereas PP2A downregulates v
      Src- and v-HaRas-induced SRE-mediated gene expression. These data suggest that
      intracellular signals activated by v-Src and mediated by HaRas are differentially
      regulated by PP2A.

PMID- 7802631
TI  - C-type natriuretic peptide inhibits intimal thickening of rabbit carotid artery
      after balloon catheter injury.
AB  - C-type natriuretic peptide (CNP) stimulated cGMP production in rabbit cultured
      vascular smooth muscle cells, and thymidine uptake was inhibited by CNP. We
      tested whether CNP inhibits the development of intimal lesions induced by balloon
      catheter injury in rabbit common carotid artery. CNP (1 microgram/kg/min)
      infusion through the left jugular vein by DIB balloon catheter pump was started
      at 30 min before injury and continued until sacrifice. The median of the mean
      ratio of intima to media in each rabbit after 14 days was 29.5% [14.5-57.8] for
      control group and 12.0% [2.5-29.8] for CNP group (p < 0.01). Maximum ratio was
      also significantly low in CNP group. These results suggest that CNP may act as
      local regulator which suppresses intimal thickening.

PMID- 7802632
TI  - Murine fibroblast growth factor receptor 1 gene generates multiple messenger RNAs
      containing two open reading frames via alternative splicing.
AB  - The arrangement of exons and introns encoding 5'-side of murine fibroblast growth
      factor (FGF) receptor 1 (FGFR-1) gene was mapped. A large intron with a size of
      14 kb was identified between exon 1 and exon 2. In addition, all FGFR-1 subtypes
      including a unique variant form with 12 amino acids insertion and two amino acids
      deletion were observed to be able to be generated through alternative splicing.
      Furthermore, complete sequencing of the 5'-region of FGFR-1 mRNA revealed that a
      relatively large open reading frame precedes the major open reading frame
      encoding FGFR-1. These results indicate that FGFR-1 mRNAs are uniquely translated
      from an internal translation start site.

PMID- 7802633
TI  - Induction of CYP2E1 in liver, kidney, brain and intestine during chronic ethanol
      administration and withdrawal: evidence that CYP2E1 possesses a rapid phase half
      life of 6 hours or less.
AB  - Controversy exists as to whether the induction of CYP2E1 by ethanol occurs via
      increased protein synthesis or protein stabilization. To address these issues in
      vivo, we chronically administered ethanol to rats and determined levels of
      immunoreactive CYP2E1 in liver, kidney, brain and upper gastro-intestinal tract
      (GI). Our data shows that chronic ethanol administration induces hepatic (5-6
      fold over pair-fed controls) and extra-hepatic CYP2E1, an effect which is
      strikingly absent 12 hours after ethanol withdrawal. No changes in CYP2E1 mRNA
      were observed at any time, suggesting these changes are mainly post-translational
      at a blood ethanol concentration of 0.15% w/v. Our experimental data indicates
      that CYP2E1 possesses a half-life of 6 hours or less in the liver and is rapidly
      degraded following the removal of ethanol. This pattern of CYP2E1 turnover was
      also observed in other tissues, suggestive of a similar mode of regulation.

PMID- 7802634
TI  - Role of HDL apolipoprotein E in cellular cholesterol efflux: studies in apo E
      knockout transgenic mice.
AB  - The role of apo E in aspects of reverse cholesterol transport was studied in
      apolipoprotein E-deficient mice. These animals develop rampant atherosclerosis.
      The efflux of cholesterol from mouse peritoneal macrophages (MPM) was 40% lower
      when induced by high density lipoprotein (HDL) from apo E-deficient mice,
      compared to the effect of HDL from normal mice. On adding apo E to apo E
      deficient HDL, cholesterol efflux from the macrophages increased by 35%,
      approaching the degree of efflux obtained with normal HDL. This HDL (normal or
      apo E-deficient)-induced cholesterol efflux was similar in peritoneal macrophages
      derived from both normal and apo E-deficient mice, suggesting that the HDL apo E
      rather than the macrophage apo E is responsible for the stimulation of cellular
      cholesterol efflux. On determining cholesterol efflux specifically from the
      macrophage plasma membrane, the level of efflux was similar for both HDL
      preparations, suggesting that apo E in HDL is important for cholesterol
      translocation to the plasma membrane, the initial step in reverse cholesterol
      transport. It is concluded that the enhanced atherosclerosis in apo E-deficient
      mice could be related, at least partly, to the impaired efflux of LDL derived
      cholesterol from macrophages of the arterial wall.

PMID- 7802635
TI  - ACPR, a STE12 homologue from Candida albicans, is a strong inducer of
      pseudohyphae in Saccharomyces cerevisiae haploids and diploids.
AB  - ACPR from Candida albicans encodes a protein antigenically related to the
      secretory acid proteinase of this yeast. Its amino terminal domain is highly
      similar to the amino terminal, DNA-binding domain of STE12 of Saccharomyces
      cerevisiae. STE12 is involved in mating of haploids and in pseudohyphae formation
      in diploids. ACPR, or its DNA-binding domain swapped into STE12, can support
      pseudohyphae formation in S. cerevisiae diploids. However, unlike STE12, these
      constructs affect the budding pattern and induce pseudohyphae formation in S.
      cerevisiae haploids as well, and this induction is independent of the nitrogen
      status of the medium. ACPR appears to be a stronger inducer of pseudohyphae than
      STE12 and is likely to be involved in the formation of pseudohyphae and hyphae in
      C. albicans.

PMID- 7802637
TI  - Nucleic acid sequence and DNase hypersensitive sites of the 5' region of the
      mouse progesterone receptor gene.
AB  - To allow study of the control of the promoter of the mouse progesterone receptor
      gene and its specific elements, we have isolated nine individual clones and
      selectively sequenced the 5' region, which includes 5' promoter sequence and the
      non-coding region. Sequence comparison was performed versus the progesterone
      receptor genes of other species. Moreover, potential estrogen response elements,
      progesterone response elements, and other transcription factor recognition sites
      were determined by sequence analysis. In addition, since it has been confirmed
      that chromatin structures are important for regulation of gene expression, we
      also examined them in different estrogen target organs using the DNase
      hypersensitivity assay. A different pattern of the DNase hypersensitivity sites
      was detected between uterus and mediobasal hypothalamus and these sites were
      close to specific recognition elements.

PMID- 7802636
TI  - Hypomethylation and hypoexpression of human CYP2E1 gene in lung tumors.
AB  - We have demonstrated the presence of CYP2E1 protein in a catalytically active
      form in lung tumors, differences being observed between the tumors and normal
      tissues from the same patients. Indeed, a higher microsomal CYP2E1 N
      nitrosodimethylamine (NDMA) demethylase activity was present in normal tissues
      compared to tumors and was accompanied by corresponding change in CYP2E1 protein
      concentration, as shown by Western blot analysis. The catalytic activity among
      tumors differed from that among normal tissues with statistical significance of p
      < 0.01. CYP2E1 mRNA was present in lung tumors and less expressed compared to
      normal tissues from the same individuals. In order to understand the regulation
      of CYP2E1 gene expression, we studied the methylation status of the CYP2E1 gene
      in human lung tumors and normal tissues from the same patients and observed that
      a hypomethylation was associated with a hypoexpression of the CYP2E1 gene in lung
      tumors.

PMID- 7802638
TI  - A cell type-dependent enhancer core element is located in exon 5 of the human
      angiotensinogen gene.
AB  - We have recently characterized a cell type-dependent downstream enhancer that is
      contained within an 832-bp B2 sequences spanning the exon 5 and 3'-flanking
      region of the human angiotensinogen gene and have localized one of core elements
      to a 24-bp region in the 3'-flanking region. In the present study, we
      functionally dissected the 5'-half of B2 region and identified an additional cell
      type-dependent enhancer core element composed of the 80-bp sequences (+1399 to
      +1478) in the exon 5. Electrophoretic mobility shift assays demonstrated that the
      element interacts with two HepG2 cell-specific and several ubiquitous nuclear
      factors. These results, together with our previous results, suggest that the 80
      bp exon 5 enhancer core element as well as 24-bp region plays an important role
      in the downstream enhancer effect.

PMID- 7802639
TI  - Functional reconstitution of Ehrlich cell plasma membrane ferricyanide reductase.
AB  - Native plasma membrane fractions isolated from Ehrlich ascites tumor cells were
      used as the starting point for two easy and efficient procedures to functionally
      reconstitute ferricyanide reductase activity. The obtained proteoliposomes showed
      high specific activities. The reconstituted ferricyanide reductase seemed to have
      one or more cysteine essential residues, as judged by inhibition with sulfhydryl
      reagents.

PMID- 7802640
TI  - Alteration of phosphoinositide metabolism by attenuation of cAMP resulting from
      expression of the H-ras oncogene.
AB  - Most studies characterizing H-ras have been conducted in constitutively
      expressing cell lines. To explore the early interaction between H-ras p21 and
      signal transduction systems we have utilized an NIH3T3 fibroblast line
      transfected with a steroid inducible MMTV H-ras vector. Exposure to dexamethasone
      resulted in transcription of H-ras accompanied by an increase in PI turnover.
      Addition of cAMP analogs restored PI metabolism to control level. We postulate
      that these effects are due to the regulatory action of PKA on PLC and that H-ras
      may interfere with cAMP metabolism, negating its regulatory effect on PLC.
      Therefore, we investigated the role of p21 in cAMP metabolism and PLC activity.
      We demonstrated that after p21 reached maximal level of expression, cAMP
      synthesis was reduced to 45% of the control. Radioimmunoassay of cAMP also
      indicated H-ras acts to inhibit adenylate cyclase activity. Further, we found a 4
      fold increase in PLC activity in H-ras expressing cells that could be reversed by
      elevation of cAMP. Incubation with the PKA inhibitor, KT5720, resulted in
      activity similar to that observed in H-ras expressing cells. Additionally, we
      have shown no correlation between H-ras expression and GTP gamma s stimulated PI
      metabolism, indicating that H-ras is not functioning as a G protein in PLC
      activation. These results imply that H-ras functions, in this system, to decrease
      levels of cAMP, thus negating the regulatory effect of PKA on PLC.

PMID- 7802641
TI  - Positive and negative regulations of human platelet-activating factor receptor
      transcript 2 (tissue-type) by estrogen and TGF-beta 1.
AB  - We found that the expression of human platelet-activating factor receptor (PAFR)
      gene is differentially regulated by estrogen and TGF-beta 1. Primer extension
      analysis revealed that the levels of the PAFR transcript 2 were increased by
      estrogen, but decreased by TGF-beta 1 in the human stomach cancer cell line (JR
      St cells) which expressed both functional endogenous PAFR transcript 1 (leukocyte
      type) and transcript 2 (tissue-type). Both ligands did not affect the expression
      of intrinsic PAFR transcript 1. Furthermore, the response elements to estrogen
      and TGF-beta 1 in the PAFR promoter 2 were delineated by a transient expression
      assay using the chloramphenicol acetyltransferase (CAT) gene as a reporter in
      this cell line. A negative response element for TGF-beta 1 was mapped on the
      sequence from -90 bp to -81 bp, which has consensus sequence for TIE (TGF-beta 1
      inhibitory element). Although consensus estrogen response element
      (AGGTCAnnnTGACCT) is not present in this promoter, the entire sequence comprising
      two AGGTCA half motifs spaced by 153 bp (from -257 bp to -93 bp) conferred weak
      but significant estrogen responsiveness. Thus, through these elements in the PAFR
      promoter 2, estrogen and TGF-beta 1 may regulate the PAFR gene to achieve a
      tissue-specific expression.

PMID- 7802642
TI  - Platelet-activating factor (PAF) positively auto-regulates the expression of
      human PAF receptor transcript 1 (leukocyte-type) through NF-kappa B.
AB  - The human platelet-activating factor receptor (PAFR) gene is transcribed by two
      distinct promoters (promoter 1 and promoter 2) to generate two transcripts
      (designated as PAFR transcript 1 and PAFR transcript 2), though their open
      reading frames are identical. By primer extension analysis to discriminate two
      transcripts, we found that the levels of PAFR transcript 1 (leukocyte-type), but
      not PAFR transcript 2 (tissue-type), are upregulated by PAF as well as by 12-O
      tetradecanoylphorbol-13-acetate (TPA) in the human stomach cancer cell line (JR
      St cells) which expresses both functional PAFR transcript 1 and PAFR transcript 2
      endogenously. Functional analysis of the promoter 1 with a transient expression
      assay using chloramphenicol acetyltransferase (CAT) gene as a reporter showed
      that both PAF and TPA activated the promoter 1 but not the deleted promoter
      lacking the three consensus binding sites for NF-kappa B located from -571 bp to 
      459 bp. These findings suggest a molecular mechanism of positive regulation of
      PAFR gene expression by PAF through NF-kappa B, possibly by a phosphorylation
      reaction involving protein kinase C by PAF.

PMID- 7802643
TI  - Nitric oxide kills hepatocytes by mobilizing mitochondrial calcium.
AB  - We have recently shown (Schweizer, M., and Richter, C. (1994) Biochem. Biophys.
      Res. Commun. 204, 169-175) that nitric oxide (nitrogen monoxide, NO) at low
      concentrations potently and reversibly deenergizes isolated liver and brain
      mitochondria at oxygen concentrations that prevail in cells and tissues. We now
      report that also in freshly prepared hepatocytes NO deenergizes mitochondria.
      Deenergization is reversible at low, but longer-lasting at higher NO
      concentrations. The drop and the recovery of the mitochondrial membrane potential
      are accompanied by a rise and fall of cytosolic Ca2+ levels. At higher
      concentrations NO kills hepatocytes. Killing is reduced when the cytosolic Ca2+
      is chelated, or when the cyclic uptake and release of Ca2+ ("Ca2+ cycling") by
      mitochondria is prevented. We conclude that NO can kill cells by deenergizing
      mitochondria and thereby flooding the cytosol with Ca2+.

PMID- 7802644
TI  - Absolute glutathione requirement for sporulation of a yeast Saccharomyces
      cerevisiae.
AB  - The glutathione (GSH)-deficient yeast cells of Saccharomyces cerevisiae
      completely failed to sporulate in nutrition-deprived medium containing potassium
      acetate (SPO medium). The sporulation defect of the yeast was restored only when
      the yeast cells were incubated in SPO medium in the presence of GSH or its
      derivative such as oxidized GSH and gamma-L-glutamyl-L-cysteine. It was concluded
      that GSH was indispensably required to enter into meiosis and/or sporulation
      processes of the yeast Saccharomyces cerevisiae.

PMID- 7802645
TI  - Inhibition of human stromelysin by peptides based on the N-terminal domain of
      tissue inhibitor of metalloproteinases-1.
AB  - The tissue inhibitors of metalloproteinases (TIMPs) represent a family of
      naturally occurring protein inhibitors of stromelysin and other members of the
      family of matrix metalloproteinases. A series of peptides based on the N-terminal
      sequence of natural TIMP-1 was synthesized and assessed for inhibitory activity
      against purified human stromelysin. Inhibitor peptides were identified in the
      loop (bounded by the disulfide bonds [C3-C99] and [C13-C124]), e.g., [C3(Acm)
      C13], (IC50, 42 microM). It was established that inhibition was due to the free
      sulfhydryl group of either C13 or C124. However, peptides within [C70(Acm)
      C98(Acm)] inhibited stromelysin independently of zinc co-ordination by cysteine.
      The binding epitope in TIMP-1 may be discontinuous and comprised of sequences
      from at least 2 loops.

PMID- 7802646
TI  - The soluble form of Alzheimer's amyloid beta protein is complexed to high density
      lipoprotein 3 and very high density lipoprotein in normal human plasma.
AB  - The amyloid fibrils of Alzheimer's neuritic plaques and cerebral blood vessels
      are mainly composed of aggregated forms of a 39 to 44 amino acids peptide, named
      amyloid beta (A beta). A similar although soluble form of A beta (sA beta) has
      been identified in plasma, cerebrospinal fluid and cell culture supernatants,
      indicating that it is produced under physiologic conditions. We report here that
      sA beta in normal human plasma is associated with lipoprotein particles, in
      particular to the HDL3 and VHDL fractions where it is complexed to ApoJ and, to a
      lesser extent, to ApoAI. This was assessed by immunoprecipitation experiments of
      purified plasma lipoproteins and lipoprotein-depleted plasma and confirmed by
      means of amino acid sequence analysis. Moreover, biotinylated synthetic peptide A
      beta 1-40 was traced in normal human plasma in in vitro experiments. As in the
      case of sA beta, biotinylated A beta 1-40 was specifically recovered in the HDL3
      and VHDL fractions. This data together with the previous demonstration that A
      beta 1-40 is taken up into the brain via a specific mechanism and possibly as an
      A beta 1-40-ApoJ complex indicate a role for HDL3- and VHDL-containing ApoJ in
      the transport of the peptide in circulation and suggest their involvement in the
      delivery of sA beta across the blood-brain barrier.

PMID- 7802647
TI  - Human serum amyloid P component binds to a specific peptide in the presence of
      calcium.
AB  - Human serum amyloid P component (SAP) binds to a carboxyl-terminal peptide of
      residues 160-204 of SAP itself in the presence of calcium. A set of sequentially
      overlapping decapeptides covering the entire length of residues 160-204 of SAP
      was synthesized on polyethylene pins to be used for binding assay, and six
      overlapping peptides in residues 190-204 (Tyr-Glu-Ile-Arg-Gly-Tyr-Val-Ile-Ile-Lys
      Pro-Leu-Val-Trp-Val) were found to have equally high affinity for SAP. The
      validity of using peptides on polyethylene pins was shown by the binding assay
      using 11-residue soluble peptide corresponding to residues 194-204. Replacement
      of the Lys or the Ile residues with Glu abolished the binding activity.

PMID- 7802648
TI  - Steroid hormone modulation of vitamin D receptor levels in human MG-63
      osteosarcoma cells.
AB  - The effects of steroid and thyroid hormones are mediated by intracellular hormone
      receptors. An important mechanism modulating target tissue responsiveness to
      hormones is homologous and heterologous regulation of the receptors. We have
      characterized the expression of steroid hormone receptors in human MG-63
      osteosarcoma cells. The MG-63 cells express receptor mRNAs for glucocorticoids,
      estrogen, retinoic acid, and 1,25(OH)2D3. We found that only the vitamin D
      receptor (VDR) mRNA concentration was influenced by the hormones. The stability
      of the VDR message was identical in control, dexamethasone- and estradiol-treated
      cells. On the other hand, both 1,25(OH)2D3 and retinoic acid separately
      stabilized the VDR mRNA levels increasing the apparent half-life by 11 h and 6 h,
      respectively. The VDR protein levels, however, as measured by
      immunoprecipitation, increased only after the 1,25(OH)2D3 treatment.

PMID- 7802649
TI  - NGF stimulates differentiation of osteoblastic MC3T3-E1 cells.
AB  - The activities of NGF on induction of IL-6, ALP and collagen were studied in
      cultured osteoblastic cells, MC3T3-E1. Treatment of the cells with NGF induced IL
      6 production in a dose dependent manner and enhanced ALP activity and collagen
      biosynthesis without affecting cell proliferation. Cyclo-oxygenase was activated
      in NGF-treated cells and prostaglandinE2 was detected as a major metabolite from
      arachidonic acid. Since prostaglandinE2 is an enhancer of ALP activity and
      collagen biosynthesis in MC3T3-E1 and was found to induce IL-6 production in this
      study, it is possible that NGF works on MC3T3-E1 cells through the mediation by
      endogenous prostaglandinE2.

PMID- 7802650
TI  - Identification of genetic variation in the human serotonin 1D beta receptor gene.
AB  - Disturbances of serotonergic pathways have been implicated in a wide variety of
      neuropsychiatric disorders such as depression, anxiety, migraine, and substance
      abuse. Genetic variation in genes coding for serotonin receptor proteins might
      well be involved in the genetic predisposition to these diseases and/or of
      pharmacogenetic relevance. Genomic samples from 46 unrelated healthy subjects
      were investigated by single-strand conformation analysis (SSCA) to screen for
      genetic variation in the human serotonin 1D beta (5-HT1D beta) receptor gene.
      Overlapping PCR (polymerase chain reaction) fragments covered the whole coding
      sequence as well as 5' untranslated regions of the 5-HT1D beta gene. Four
      nucleotide sequence variants were found: a coding mutation in nucleotide position
      371 which leads to an amino acid exchange (Phe-->Cys) in position 124 of the
      receptor protein and three mutations in the 5' flanking region. For all mutations
      specific PCR-based assays were developed which allow rapid genotyping in
      populations and families. To our knowledge, the Phe-124-Cys substitution is the
      first natural occurring molecular variant which has been identified for the 5
      HT1D beta receptor so far.

PMID- 7802651
TI  - WWP, a new amino acid motif present in single or multiple copies in various
      proteins including dystrophin and the SH3-binding Yes-associated protein YAP65.
AB  - A new repeating amino acid motif, which we called WWP, was found in several
      proteins of yeast, nematod or vertebrate origin. Among these are dystrophin, the
      product of the Duchenne muscular dystrophy locus, a protein (YAP65) which
      associates in vitro with the Src homology domain 3 (SH3) of the Yes proto
      oncogene product, and a human putative GTPase-activating protein. As is the case
      for proteins which contain the SH2, SH3 and PH domains, at least some of the WWP
      containing proteins appear to be signaling or cytoskeletal proteins, associated
      with plasma or organellar membranes, and specific protein-protein contacts are
      likely to be crucial to their function.

PMID- 7802652
TI  - Purification of a cell-cell adhesion regulator from porcine seminal vesicle
      fluid.
AB  - Seminal plasma derived factors are implicated in mediating inflammation in the
      female reproductive tract following insemination at mating. During inflammation,
      leukocytes are activated to express adhesion receptors resulting in adherence to
      each other and for the ECM as well as for various cell types. The present study
      describes the purification of a leukocyte cell-cell adhesion regulator derived
      from seminal vesicle fluid. Seminal vesicle fluid proteins were chromatographed
      by cation exchange, hydrophobic interaction and reversed phase. Chromatography on
      Phenyl Superose resolved two distinct forms of cell-cell adhesion regulation,
      type I and II. Reversed phase chromatography of fractions inducing type I
      adhesion resulted in the isolation of a 15kDa adhesion inducing protein (pAIF-1).
      The N-terminal sequence contained a hydrophobic consensus sequence which exists
      in: two bovine seminal vesicle proteins (BSPA3, PDC 109); IGF-II receptor;
      fibronectin; and the cation independent mannose-6-phosphate receptor.

PMID- 7802653
TI  - Regulation of mouse UBF gene by multiple growth-related control elements.
AB  - Transcription of the mouse Upstream Binding Factor (mUBF) gene, that encodes one
      of the essential transcription factors for ribosomal DNA transcription, starts
      from several nucleotides. Neither typical TATA-box nor CCAAT-box is found
      upstream of the transcription initiation site. In the promoter region, there are
      eight GC-boxes, eight AP-2 binding consensus sequences, four cAMP response
      elements, and several serum response element equivalent sequences. These elements
      appear to play a positive role for the regulation of the mUBF gene as a whole.
      Among serum response elements, members located between -1182 and -343 are indeed
      responsive to serum, suggesting their important role in the high expression of
      mUBF under cell growth conditions.

PMID- 7802654
TI  - Islet amyloid polypeptide stimulates cyclic AMP accumulation via the porcine
      calcitonin receptor.
AB  - CHO-cells stably transfected with an expression vector for the porcine calcitonin
      receptor were exposed to various concentrations of IAPP, CGRP or calcitonin from
      different species. In these, but not in untransfected cells, rat IAPP mediated
      cAMP accumulation at concentrations above 25 nM. This potency was three orders of
      magnitude lower than that of porcine calcitonin and two and four orders of
      magnitude lower than those of human and salmon calcitonin, respectively. Human
      beta-CGRP had an effect similar to rat IAPP whereas human alpha-CGRP was at least
      one order of magnitude less potent than rat IAPP. COS cells expressing
      recombinant porcine calcitonin receptors transiently or stably showed a different
      pattern of responses to calcitonin, IAPP and the CGRPs. In these cells, rat IAPP
      was as potent an inducer of cAMP as was salmon or porcine calcitonin and more
      potent than human calcitonin or the CGRPs. The dissociation constants for salmon
      calcitonin binding to the porcine calcitonin receptors on CHO and COS cells were
      0.2 nM and 2.0 nM and the corresponding number of binding sites per cell were
      approximately 7 x 10(4) and 2 x 10(6), respectively. These results demonstrate
      that IAPP and CGRP can mediate signal transduction via the porcine calcitonin
      receptor and provide a possible explanation for the calcitonin-like effects of
      pharmacological levels of IAPP and CGRP administrated in vivo. The difference
      between CHO and COS cells in their relative response to the various ligands may
      relate to the difference in receptor number, post-transcriptional processing, or
      to dissimilarities in the signal transduction pathways between the two cell
      types.

PMID- 7802655
TI  - Characterization of FIII/YY1, a Xenopus laevis conserved zinc-finger protein
      binding to the first exon of L1 and L14 ribosomal protein genes.
AB  - The cDNA coding for the Xenopus laevis homolog of the transcriptional
      activator/repressor protein delta/YY1 was isolated from a lambda gt11 oocyte cDNA
      library. The deduced aminoacid sequence shows that the four zinc fingers of the
      DNA binding domain are 99% conserved when compared to the mouse (delta) and 95%
      to the human (YY1) proteins, while differences are found in the N-terminal
      region. In particular, the long run of consecutive glycines and histidines of
      delta and YY1 is missing. The protein, named FIII/YY1, was overexpressed into
      Xenopus oocytes from the cDNA under direction of the L14 rp-promoter and found to
      share antigenic and DNA-binding properties with the oocyte endogenous protein
      binding to the first exon of the X.laevis ribosomal protein genes (rp-genes) L1
      and L14.

PMID- 7802656
TI  - HIV-1 modulates the expression of gelatinase A and B in monocytic cells.
AB  - The levels of mRNA of both gelatinases A and B were dramatically decreased in HIV
      infected cells, when compared to uninfected cells. The expression of gelatinase A
      in HIV-infected cells was selectively increased by tumor necrosis factor (TNF
      alpha) while the expression of gelatinase B was not affected. In contrast, in
      uninfected cells TNF alpha down regulated gelatinase B mRNA level, without
      affecting the gelatinase A. N-acethylcysteine (NAC) increased the levels of mRNA
      of both gelatinases. The conditioned media from HIV-infected and uninfected cells
      had comparable level of secreted gelatinase A protein. These data suggest that in
      monocytic cells different regulatory pathways control gelatinases A and B and
      that HIV could modulate in vivo the expression of these proteolytic enzymes,
      critically involved in regulation of invasion of basement membrane.

PMID- 7802657
TI  - Isolation and characterization of the gene encoding rat class theta glutathione S
      transferase subunit yrs.
AB  - The rat gene encoding the class theta glutathione S-transferase (GST) subunit Yrs
      has been isolated from a rat lambda EMBL4 DNA library and completely sequenced.
      The gene spans approximately 4 kb comprising 5 exons separated by 4 introns, the
      smallest number of the gene components among known rat genes encoding GST
      subunits. Sequence analysis of the 5' flanking region of the GST Yrs gene
      indicated the absence of both TATA and CAAT boxes. However, potential binding
      sites for the transcription factors SP1, PU1, PEA3, and AP-2 were present in this
      region. Primer extension and 5'-rapid amplification of cDNA ends studies
      demonstrated the existence of multiple transcription initiation sites distributed
      over 58 bp in the upstream sequence from the translation initiation codon. The
      present study provides the first evidence for the primary structure of the gene
      encoding a class theta GST subunit.

PMID- 7802658
TI  - The development of fatty liver is accelerated in transgenic mice expressing
      cynomolgus monkey cholesteryl ester transfer protein.
AB  - Expression of cynomolgus monkey cholesteryl ester transfer protein (CETP) in
      C57BL/6 mice has been shown to have a profound effect on the lipoprotein profile
      in those animals. The objective of this study was to examine the effect of CETP
      expression on the hepatic lipids of the CETP transgenic mice. The triglyceride,
      cholesterol and phospholipid composition of livers from 6- and 12-month-old
      transgenic mice were evaluated and compared with those of age-matched C57BL/6
      mice. Statistical analysis indicated that fatty liver was more severe in CETP
      transgenic mice than C57BL/6 controls (p < 0.01); progressed with age (p < 0.01);
      and developed more rapidly in males than females (p < 0.01). The lipid that
      accumulated was triglyceride. These data indicate that CETP expression
      accelerates the development of fatty liver in the C57BL/6 mouse and raise the
      possibility that CETP may also contribute to the process of hepatic steatosis in
      man.

PMID- 7802659
TI  - Two different enzymes are primarily responsible for retinoic acid synthesis in
      rabbit liver cytosol.
AB  - Retinoic acid biosynthesis in rabbit liver was catalyzed by cytosolic NAD(+)
      dependent dehydrogenase and oxygen-dependent oxidase, with an activity ratio of
      59% and 41% in the presence of 2 mM dithiothreitol under aerobic conditions. The
      two enzymes could be well separated by fractionation involving ammonium sulfate
      precipitation. Purification of the enzymes indicated that the oxygen-dependent
      enzyme was a flavoenzyme, retinal oxidase (EC 1.2.3.11), composed of two 135 kDa
      subunits; and the NAD(+)-dependent enzyme was a basic pI retinal dehydrogenase
      composed of four 55-kDa subunits. A high concentration (1-2 mM) of DTT was
      required to stabilize the activity of retinal dehydrogenase during the
      purification procedures and storage, but inhibited the activity of retinal
      oxidase by 13-38%. The physiological roles of the two retinoic acid synthases in
      liver cytosol were discussed.

PMID- 7802660
TI  - Nuclear localization signals in the core protein of hepatitis C virus.
AB  - The core protein of the hepatitis C virus is derived from the N-terminal 191
      amino acids of the viral polyprotein by proteolytic cleavage. In the current
      study, subcellular localizations of the HCV core and its beta-galactosidase
      fusion proteins in transfected cells were examined by indirect immunofluorescence
      and cytochemical staining. The core protein was located predominantly in the
      cytoplasm 6 days after a plasmid encoding the full-length core protein had been
      introduced into mammalian cells. A hydrophobic domain in the C-terminal region of
      the core protein may block the efficiency of nuclear transport, since a beta
      galactosidase fusion protein that contains HCV core protein lacking the C
      terminal 66-amino-acid was located within the nuclei of mammalian cells 24 hours
      posttransfection. Three independent nuclear localization signals were further
      identified in the N-terminal region of the HCV core protein.

PMID- 7802661
TI  - Molecular construction of Clostridium botulinum type C progenitor toxin and its
      gene organization.
AB  - The 16S progenitor toxin of Clostridium botulinum type C is made up by
      conjugation of a neurotoxin with nontoxic components designated as nontoxic-nonHA
      and hemagglutinin (HA). The HA was found to be composed of subcomponents having
      53, 33, 22-23, and 17 kDa molecular masses. Since we previously determined the
      whole nucleotide sequences of the genes for neurotoxin, nontoxic-nonHA, and HA
      33, the cloning and nucleotide sequencing of the genes for the remaining HA
      subcomponents were performed. Two open reading frames coding for 16.7 kDa (HA-17)
      and 70.6 kDa proteins were identified. The N-terminal amino acid sequences of HA
      53 and HA-22-23 indicated that the 70.6 kDa protein is split into 53 and the 22
      23 kDa proteins after translation and that the 22-23 kDa protein consists of at
      least four proteins showing slightly different molecular weights.

PMID- 7802662
TI  - Loss of DNA binding ability of the transcription factor encoded by the mutant mi
      locus.
AB  - The mi locus of mice encodes a novel member of the basic-helix-loop-helix-leucine
      zipper protein family of transcription factors (MITF). Mutant mice of the mi/mi
      genotype have the deletion of an arginine in the basic domain and show the
      abnormality in development of eyes, melanocytes, osteoclasts and mast cells. The
      expression of the mast cell protease 6 (MMCP-6) gene is markedly reduced in mi/mi
      mice. We examined the in vitro binding ability of the normal and mutant MITF to a
      hexameric motif (CACATG) located in the 5'-flanking sequence of the MMCP-6 gene.
      The normal MITF bound the hexameric motif but the mutant MITF did not, suggesting
      that the MITF directly regulated the expression of the MMCP-6 gene.

PMID- 7802663
TI  - Novel role of vitamin K2: a potent inducer of differentiation of various human
      myeloid leukemia cell lines.
AB  - When myeloblastic ML1 cells were cultured in the presence of Vitamin K2
      (menaquinone, VK2), the population of cells capable of reducing NBT increased to
      83.5% at low VK2 concentration of 1 microM, indicating VK2 induces cellular
      differentiation. VK2 also exerted differentiation-inducing action on histiocytic
      U937 and promyelocytic HL60 cell lines. None of these effects were observed with
      Vitamin K1 (phylloquinone, VK1), suggesting the geranylgeranyl group of the side
      chain of VK2 to be essential to these effects. Combinations of VK2 with other
      differentiation-inducers such as interferon-gamma, retinoic acid, or camptothecin
      additively or synergistically induced the differentiation of HL-60 cells. These
      results suggest that VK2 may safely be used in differentiation therapy in
      combination with other inducers.

PMID- 7802664
TI  - Mechanism of adenovirus-mediated endosome lysis: role of the intact adenovirus
      capsid structure.
AB  - Adenoviruses have been previously shown to enhance the delivery of many ligands
      including proteins and plasmid DNAs to the cells. The key biochemical step during
      this process is the ability of adenovirus to disrupt (lyse) the endosome membrane
      releasing the co-internalized virus and the other ligands into the cytosol (Seth
      et al, 1986, In: Adenovirus attachment and entry into cells, pp 191-195, American
      Society for Microbiology, Washington, D.C.). To understand the role of the
      adenovirus proteins involved in the endosome lysis, it is further shown here that
      empty capsids of adenovirus also possess this membrane vesicle lytic activity;
      though the activity is about 5-times lower than the adenovirus. Incubation of
      adenovirus with low concentration of ionic detergent or brief exposure to 45
      degrees C destroyed this lytic activity without affecting the adenovirus binding
      to cell surface receptor, suggesting the lytic activity of adenovirus to be of
      enzymatic nature. However, exposing adenovirus to conditions that can disrupt
      adenovirus capsid structure such as heating at 65 degrees C, treating with 0.5%
      SDS, treating with different proteases, dialyzing against no glycerol buffer,
      treating with 6 M urea or with 10% pyridine, and sonication destroyed the
      adenovirus-associated lytic activity. Results suggest the requirement of an
      intact capsid structure for adenovirus-mediated lysis of the endosome.

PMID- 7802665
TI  - Genomic organization and DNA sequence of the human catecholamine-sulfating phenol
      sulfotransferase gene (STM).
AB  - The human monoamine neurotransmitter-preferring phenol sulfotransferase (M-PST)
      plays an essential role in the sulfation of catecholamines, such as dopamine. The
      cDNA encoding M-PST has been reported, and we have recently identified cosmid
      clones from human chromosome 16p11.2 for this gene, STM. Plasmid subclones
      derived from the STM cosmid clones were subjected to dideoxynucleotide chain
      termination sequencing to determine the genomic organization and DNA sequence of
      STM. The gene encoding full-length STM is approximately 6.4 kb and contains 8
      exons and 7 introns.

PMID- 7802666
TI  - Carbon monoxide as an endogenous modulator of hepatic vascular perfusion.
AB  - Carbon monoxide (CO) generated by heme oxygenase has recently been considered a
      neural messenger in brain. This observation prompted us to investigate whether CO
      participates in vascular regulation in the liver, another organ with high levels
      of heme oxygenase activity. In isolated perfused rat liver, submicromolar levels
      of CO were detectable in the effluent and were able to be suppressed by the
      administration of Zn protoporphyrin IX (1 microM), a potent inhibitor of heme
      oxygenase. Furthermore, zinc protoporphyrin IX (1 microM) promoted an increase in
      the perfusion pressure under the constant flow conditions. These changes were
      reversed by adding CO (2 microM) or a cGMP analogue 8-bromo-cGMP (1 microM) in
      the perfusate. The present findings indicate that CO can function as an
      endogenous modulator of vascular perfusion in the liver.

PMID- 7802667
TI  - Participation of diacylglycerol kinase in mitogenic signal transduction induced
      by platelet-derived growth factor in vascular smooth muscle cells.
AB  - In rat vascular smooth muscle cells, platelet-derived growth factor (PDGF),
      stimulated phosphatidic acid synthesis by activating both of the two alternative
      pathways, diacyglycerol kinase (DGK) and phospholipase D (PLD). Genistein, a
      tyrosine kinase inhibitor, inhibited PLD activation but not DGK activation, the
      latter was inhibited selectively by R 59022. PDGF-induced DNA synthesis was
      partially inhibited by genistein or R 59022, but these inhibitors had no effect
      on phorbol ester-induced DNA synthesis. Further, the specific effects of these
      inhibitors on PDGF-induced DNA synthesis were additive.

PMID- 7802668
TI  - Fluid shear stress increases the expression of thrombomodulin by cultured human
      endothelial cells.
AB  - Endothelial cells (ECs) cultured from human umbilical vein were exposed to medium
      flow in a flow-loading chamber, and changes in thrombomodulin (TM) expression
      were examined by flow cytometry and enzyme linked immunosorbent assay with
      monoclonal antibody. The expression of TM antigen was increased time- and shear
      stress-dependently by flow, and when exposed to a shear stress of 15 dynes/cm2
      for 24 hr, it increased to approximately 200% of the stationary control level.
      Reverse transcriptase-polymerase chain reaction showed that TM mRNA levels in ECs
      also increased in response to flow. TM mRNA began to increase one hour after the
      application of shear stress of 15 dynes/cm2 and reached a maximum (approximately
      330% of stationary control) after eight hours. These results, demonstrating an up
      regulating effect of flow on TM expression in ECs, suggest that shear stress may
      be an important modulator of intravascular blood coagulation.

PMID- 7802669
TI  - Structure and chromosomal mapping of genes for the mouse kappa-opioid receptor
      and an opioid receptor homologue (MOR-C).
AB  - Recent cDNA cloning studies have defined four members of the opioid receptor
      family, i.e., delta-, mu- and kappa-subtypes, and an opioid receptor homologue
      for unknown ligands. In this report, we isolated and analyzed mouse genomic DNA
      segments containing the kappa-opioid receptor gene and a gene for the opioid
      receptor homologue (designated as MOR-C). The genes are closely related each
      other in exon-intron organization, suggesting their evolutional relationship.
      Using in situ hybridization, we show that the kappa-opioid receptor gene and the
      MOR-C gene map to mouse chromosome 1A2-3 and 2H2-4, respectively.

PMID- 7802670
TI  - Destruxin B, a specific and readily reversible inhibitor of vacuolar-type H(+)
      translocating ATPase.
AB  - Destruxin B, a peptide antibiotic, inhibits vacuolar-type ATPase (V-ATPase)
      specifically and dose-dependently among ATPases examined. Acidification of
      intracellular organelles is also blocked by destruxin B at comparable
      concentrations when assessed by accumulation of acridine orange. The inhibitory
      activity of destruxin B is weaker than that of bafilomycin A1 and folimycin, well
      known macrolide inhibitors of V-ATPase, when compared at the same molar
      concentration. Unlike the macrolide antibiotics, however, the inhibitory activity
      of destruxin B is readily reversible. This novel feature of destruxin B should
      make it a useful probe in the analysis of V-ATPase function in cell physiology.

PMID- 7802671
TI  - Tissue-dependent alternative splicing of mRNA for NACP, the precursor of non-A
      beta component of Alzheimer's disease amyloid.
AB  - A cDNA clone encoding an alternatively spliced form of the precursor of the non-A
      beta component of Alzheimer's disease amyloid (NACP) was isolated from a human
      fetal brain cDNA library. This cDNA contains the entire NAC coding sequence but
      lacks an 84-base-pair nucleotide stretch 3' to the NAC sequence, resulting in a
      112-amino-acid protein, NACP112, in contrast with the originally cloned molecule,
      NACP140. RT-PCR analysis demonstrated that the mRNA for two types of NACP mRNA
      are expressed in both fetal and adult brain. Northern blot analysis revealed that
      NACP140 mRNA was expressed mostly in brain and in minor amount in all the tissues
      examined. However, the expression levels of NACP140 mRNA apart from brain were
      higher in heart, skeletal muscle, and pancreas, contrasting with the predominant
      expression of total NACP mRNA in brain with a slight expression in placenta.
      These results suggest differential regulation of NACP RNA splicing among tissues.

PMID- 7802672
TI  - Purification to homogeneity of mitochondrial acyl coa:glycine n-acyltransferase
      from human liver.
AB  - Mitochondrial acyl CoA:glycine N-acyl transferase (ACGNAT) was purified to
      homogeneity from adult human liver. It was found to be a monomer of 30 kD, having
      a pI of 6.8. ACGNAT retained 47% of enzymatic activity at 100 mM NaCl
      concentration, whereas 21% of the activity was retained with KCl and 32% with
      K3PO4 at 100 mM concentration as compared to the control. The stability studies
      revealed no change in activity at 4 degrees C for up to 72 h, 25 degrees C for 4
      h and at 37 degrees C for 1 h. The Km values of human ACGNAT for benzoyl CoA,
      salicyl CoA, isovaleryl CoA and octanoyl CoA were 57.9, 83.7, 124 and 198 mM,
      respectively, and the corresponding Vmax values were 17.1, 10.1, 7.64 and 3.3
      mumol/min/mg protein. The availability of pure human ACGNAT would help in
      studying the molecular genetics and structural biology of this protein which is
      important in the detoxification of various endogenous and xenobiotic acyl CoA's.

PMID- 7802673
TI  - Mutation analysis of the role for the carboxy-terminus encoding region in NGF
      induced stabilization of GAP-43 mRNA.
AB  - NGF-induced stabilization of rat GAP-43 mRNA has been shown to be mediated by the
      292 nt segment including both 3' untranslated region and a 115 nt segment
      encoding the carboxy-terminus region. Further analysis shows that the 115 nt
      segment, which is additionally inserted just downstream from the open reading
      frame, abolished most of the stabilizing effect of NGF. On the contrary, an in
      frame insertion of the 115 nt segment just upstream from the termination codon
      does not affect the stabilization. Frameshift mutation of the segment encoding
      the carboxy-terminus region also abolishes the NGF effect. These findings suggest
      an essential role for the direct translation of the mRNA segment encoding the
      carboxy-terminus region in the stability regulation mediated by the 292 nt
      segment. In addition, presented results suggest a role for the cis interaction
      between the sub-segments in the 292 nt segment, which are the part of the
      3'untranslated region and the segment for the carboxy-terminus.

PMID- 7802674
TI  - The antigen/antibody specificity exchanger: a new peptide based tool for re
      directing antibodies of other specificities to recognize the V3 domain of HIV-1
      gp120.
AB  - We recently showed that a synthetic peptide corresponding to the third
      complementary determining region of the heavy chain (CDRH3) of a monoclonal
      antibody (mAb) directed to the V3 domain of HIV-1 gp120 neutralizes HIV-1 in
      vitro. From the CDRH3 sequence we have now produced bifunctional antigen/antibody
      specificity exchanger (A/ASE) peptides containing both the HIV-1 mAb derived
      CDRH3 sequence and antigenic region sequences from the hepatitis B virus core/e
      antigen (HBc/eAg) and the poliovirus VP1. These A/ASE peptides were able to re
      direct HBc/eAg and enteroviral VP1 specific mAbs, as well as polyclonal human HIV
      1 negative sera to recognize the V3 domain of HIV-1. Furthermore, two out of
      three A/ASE peptides were able to neutralize HIV-1 in vitro. These bifunctional
      A/ASE peptides have a potential to be used as tools in research, diagnostics and
      maybe even therapeutics.

PMID- 7802676
TI  - Molecular cloning and sequence analysis of a human 372-kDA protein localized in
      the Golgi complex.
AB  - Autoantibodies from a patient with chronic rheumatoid arthritis recognized an
      antigen localized in the Golgi complex of various cells from different tissues
      and species. The autoantibodies were used as a probe for screening human QGP-1
      cDNA library, resulting in identification of a 10.3-kb cDNA. The cDNA insert
      contained an open reading frame which encodes a 3225-residue protein with a
      calculated mass of 372 kDa. The predicted protein was found to have no NH2
      terminal signal sequence but a single hydrophobic domain at the COOH terminus.
      These results indicate that the 372-kDa antigen is cytoplasmically disposed and
      anchored to the Golgi membrane by the COOH-terminal hydrophobic domain.

PMID- 7802675
TI  - Deficiency of endogenous arginine synthesis provokes hypertension by exhausting
      substrate arginine for nitric oxide synthesis.
AB  - Effect of deficiency in endogenous arginine synthesis was studied in connection
      with NO synthesis and blood pressure. Rats with massive resection of small
      intestine were fed an arginine-free diet (AF rats) for 24 days. Control rats were
      pair-fed an isonitrogenous and isocaloric arginine-replete diet. AF rats lost
      weight by a mean of 28 g whereas control rats kept original weight. Urinary
      excretion of nitrate and cGMP was reduced in AF rats by about 40% after the
      feeding. Blood pressure became elevated by 20-25 mmHg in AF rats after the
      feeding. The concentrations of arginine in muscle and plasma of AF rats were
      reduced to 17 and 39%, respectively, of control rats. AF rats may be a novel
      animal model for the in vivo study of NO.

PMID- 7802677
TI  - Identification of a rabphilin-3A-interacting protein as GTP cyclohydrolase I in
      PC12 cells.
AB  - Rabphilin-3A is a putative target protein for Rab3A small GTP-binding protein
      which is implicated in neurotransmitter release. To identify a Rabphilin-3A
      interacting protein, proteins were immunoprecipitated by an anti-Rabphilin-3A
      polyclonal antibody from the lysate of PC12 cells and subjected to sodium dodecyl
      sulfate polyacrylamide gel electrophoresis followed by protein staining. Several
      proteins were coimmunoprecipitated with Rabphilin-3A and one of these proteins
      with a M(r) of about 30 KDa was phosphorylated in intact PC12 cells stimulated by
      high KCl. The amino acid sequence analysis of this 30 KDa protein revealed that
      it is GTP cyclohydrolase I.

PMID- 7802678
TI  - Ras activity is required for phenylephrine-induced activation of mitogen
      activated protein kinase in cardiac muscle cells.
AB  - The mitogen-activated protein (MAP) kinases are a family of kinases whose
      activity is implicated in a number of growth and differentiation responses.
      Recently, we and others have shown that these kinases are activated by agonists
      which induce cardiac muscle cell hypertrophy. Inhibition of MAP kinase activation
      prevents some of the phenotypes associated with phenylephrine-induced cardiac
      cell hypertrophy, indicating that this activation is of functional significance.
      In this communication, we show that active Ras can induce MAP kinase activation
      in cardiac muscle cells. In addition, phenylephrine-induced activation of the MAP
      kinases requires Ras activity since a dominant negative Ras mutant (Ala15Ras) and
      a Ras-blocking, Raf mutant (C4B Raf) prevent activation of the MAP kinase Erk2 by
      phenylephrine. These data indicate that phenylephrine signaling to the MAP
      kinases is mediated through Ras.

PMID- 7802679
TI  - Brain uptake of circulating apolipoproteins J and E complexed to Alzheimer's
      amyloid beta.
AB  - Amyloid beta (A beta) is a fibrillar component in Alzheimers' disease amyloid
      deposits and a soluble peptide (sA beta) normally present in body fluids. We have
      recently reported that the blood-brain barrier (BBB) has a capability to control
      cerebrovascular sequestration and transport of circulating sA beta. In this
      study, we examined whether two circulating amyloid-associated proteins shown to
      bind sA beta, apolipoproteins J (apo J) and E (apo E), can cross the BBB alone
      and/or complexed to a synthetic peptide homologous to a major form of sA beta, sA
      beta 1-40. Brain perfusion experiments in guinea pigs showed significant uptake
      of both apo J and sA beta 1-40-apo J complexes. In contrast, blood-brain
      transport of sA beta 1-40-apo E was negligible, while apo E had a limited access
      across the BBB, indicating that the apo E found within the brain is produced
      locally. It is concluded that sA beta 1-40 binding to apo J and apo E results in
      significant (> 100-fold) difference in brain uptake of their respective
      complexes. We hypothesize that in normal brain apo J facilitates sA beta
      transport.

PMID- 7802680
TI  - Distinct distributions of mu, delta and kappa opioid receptor mRNA in rat brain.
AB  - We present a comprehensive comparison of the anatomical distributions of the
      cloned mu, delta and kappa opioid receptor mRNA in rat brain. Northern blot
      analysis revealed that mRNA species encoding the three receptors differed in size
      and were differentially localized in brain regions. In peripheral tissues
      analyzed, the 3 mRNA species were detected only in the spinal cord. The
      distributions of mu, delta and kappa receptor mRNA in rat brain were examined by
      in situ hybridization histochemistry using gene-specific probes. Mu receptor mRNA
      was predominately localized to thalamic, brainstem and reticular core nuclei and
      was highest in the habenular and thalamic nuclei. In contrast, kappa receptor
      mRNA was expressed in hippocampus including dentate gyrus, hypothalamic and some
      thalamic nuclei and also present in cortex, caudate putamen, olfactory tubercle
      and nucleus accumbens. Delta receptor mRNA was prominent in cerebral cortex,
      olfactory tubercle, hippocampus, caudate putamen and nucleus accumbens. These
      results show that the mRNA distribution for each opioid receptor subtype in brain
      is unique and correlate well with the known distribution of the corresponding
      opioid receptor binding sites.

PMID- 7802682
TI  - In vitro translation of D2 dopamine receptors and their chimaeras: analysis by
      subtype-specific antibodies.
AB  - We have developed a range of specific anti-peptide antibodies directed against
      the D2 and D3 dopamine receptors, and their alternatively spliced isoforms. To
      demonstrate the subtype- and isoform-specificities of these antibodies we have
      expressed the receptors in an in vitro translation system and have
      immunoprecipitated the expressed proteins. We have shown that the D2 and D3
      receptors unexpectedly exhibit different migration properties on SDS-PAGE, in
      addition to displaying a significant difference between their predicted and
      apparent molecular weights. We have used D2/D3 chimaeric receptors to show that
      the differential migration between the subtypes can be attributed to the N
      terminal half of the receptor and propose that the highly hydrophobic nature of
      the receptor proteins underlies their anomalous migration properties.

PMID- 7802681
TI  - Hepatocyte growth factor region specifically stimulates gastro-intestinal
      epithelial growth in primary culture.
AB  - Hepatocyte growth factor (HGF) stimulated the growth of fetal rat
      gastrointestinal epithelial cells in primary culture with a clear dose-response
      relationship. The epithelial response to the mitogenic activity of HGF was
      different among the region of the gastro-intestinal tract; glandular stomach most
      responsive, followed by intestine and forestomach. The interaction of HGF with
      other growth factors in inducing the epithelial growth was also different
      depending on the type of the epithelial cells, indicating a region-specific
      growth regulation in the gastro-intestinal tract. Analyses using Northern blot
      and RT-PCR revealed that HGF mRNA was expressed only in mesenchymes but not in
      epithelia of the gastro-intestinal tract while expression of c-met (HGF receptor)
      gene was observed in both tissues. These results suggest that gastro-intestinal
      mesenchymes secrete HGF which stimulates the growth of attaching epithelial cells
      by a paracrine mechanism, and that the epithelial response to HGF is controlled
      by a region-specific growth regulatory mechanism.

PMID- 7802683
TI  - A substrate of ecto-protein kinase is microtubule-associated protein 1B in
      cortical cell cultures undergoing synaptogenesis.
AB  - Synapse formation between cultured rat cortical neurons is inhibited by the
      continuous application of K-252b, an ecto-protein kinase inhibitor, which cannot
      permeate the cell membrane. In order to identify the phosphorylated membrane
      proteins which are necessary for synapse formation, endogenous substrates for
      ecto-protein kinase activity were investigated. To detect phosphorylation of
      proteins containing extracellular domains, [gamma-33P]ATP was applied to the
      medium for brief periods. Proteins were then separated by SDS polyacrylamide gel
      electrophoresis and detected by autoradiography. Some bands showed immediate
      phosphorylation and this phosphorylation was suppressed by the addition of K-252b
      to the medium. We examined partial amino acid sequences of these substrates. The
      band with the highest molecular weight, whose phosphorylation was strongly
      inhibited by K-252b, was identified as microtubule-associated protein (MAP) 1B.
      These results suggest the possibility that the phosphorylation of extracellular
      domains of MAP1B is involved in synaptogenesis between cortical neurons.

PMID- 7802684
TI  - Okadaic acid, an inhibitor of type 1 and type 2A phosphatases, modulates the
      activation of phospholipase D in formyl peptide- and mastoparan-stimulated human
      neutrophils.
AB  - The activation of phospholipase D (PLD) induced by formyl peptides (fMLP), as
      evaluated by production of tritiated phosphatidylethanol (PEt) and phosphatidic
      acid (PA) in polymorphonuclear leukocytes (PMN), was markedly enhanced (50-125%)
      by low okadaic acid concentrations (0.25-0.5 microM) but inhibited by higher
      concentrations (2-3 microM), although the drug caused protein
      hyperphosphorylation. Both effects of okadaic acid were amplified when PLD
      activation was primed with cytochalasin B. Stimulation of PMN with mastoparan, a
      wasp venom toxin that activates Pertussis toxin(PTX)-sensitive G proteins,
      resulted in a weak calcium-dependent production of PEt which was respectively
      enhanced and inhibited by okadaic acid (1-2 microM) in unprimed and cytochalasin
      primed PMN. The results show that low okadaic acid concentrations primed fMLP
      mediated activation of PLD, in keeping with a down-regulatory role of protein
      phosphatases. The contrasting effects of okadaic acid in mastoparan-stimulated
      PMN further suggest that protein phosphatases may regulate the generation of
      second messengers through alteration of major signaling events at/or downstream
      of PTX-sensitive G proteins (Gi).

PMID- 7802685
TI  - Lupus anticoagulant autoantibody induces apoptosis in umbilical vein endothelial
      cells: involvement of annexin V.
AB  - The effects of lupus anticoagulant (LAC) on cultured human umbilical vein
      endothelial cells were studied. All five monoclonal antibodies from a patient
      with systemic lupus erythematosus (SLE), as well as plasma samples with LAC
      activity from six SLE patients, induced apoptosis. Anti-annexin V IgG also
      induced apoptosis. Since monoclonal antibodies and plasma from SLE patients had
      an affinity for annexin V, an endothelial apoptosis pathway mediated by annexin V
      was suggested as the molecular pathogenesis of the hemostatic derangement
      associated with LAC.

PMID- 7802686
TI  - Cloning of a novel putative protein kinase having a leucine zipper domain from
      human brain.

PMID- 7802687
TI  - Decidua is a possible source of serum mouse soluble interleukin-6 receptor (msIL
      6R): gestational profile of serum msIL-6R concentration.
AB  - The serum concentration of msIL-6R of 10 weeks old virgin ICR mouse assessed by a
      RIA was 45.6 +/- 6.6 ng/ml. The serum msIL-6R concentration of the pregnant mouse
      mated at 10 weeks of age was 41.2 +/- 3.0 ng/ml on day 7 of pregnancy. The serum
      concentration gradually increased during gestation and reached peak on day 17 of
      pregnancy (149.1 +/- 13.7 ng/ml). On the third day of the puerperium, the serum
      msIL-6R concentration of the mother from which the pups had been removed on the
      day of delivery was decreased to the level of that on day 7 of pregnancy. IL-6R
      mRNA level in the decidua significantly increased during mid and late gestational
      stages. msIL-6R was detected in the medium of cultured decidual cells (8.03 +/-
      0.28 ng/ml), but not placental cells. Western analysis for msIL-6R using the
      conditioned medium of the cultured decidual cells resulted in a single band at
      approximately 45 K. To find out a biological role of msIL-6R during gestation,
      placental cells were incubated with mIL-6 and msIL-6R, and mPL-I concentration in
      the medium was assessed by RIA. 2.5 nM mIL-6 did not affect the secretion of mPL
      I in placental cells; however, addition of msIL-6R resulted in a significant
      stimulation of mPL-I secretion. These results suggest that serum msIL-6R, which
      is likely to be secreted from decidua, may play an important role during
      gestation.

PMID- 7802688
TI  - Voltage-independent calcium channels. Regulation by receptors and intracellular
      calcium stores.

PMID- 7802689
TI  - Activation of diacylglycerol kinase by carbachol in guinea pig taenia coli.
AB  - Changes in diacylglycerol kinase (DG kinase) activity in carbachol (CCh)
      stimulated guinea pig taenia coli were investigated. In a mixed micellar assay
      system, added 1,2-dioctanoyl-sn-glycerol (diC8) and endogenous DG were
      competitively bound to common DG kinase isozymes from guinea pig taenia coli and
      phosphorylated, suggesting that diC8 is useful as a probe of agonist effects on
      DG kinase activity. In phosphorus-32 ([32P]Pi)- and diC8-prelabeled guinea pig
      taenia coli, diC8 was phosphorylated by DG kinase to [32P]dioctanoyl-phosphatidic
      acid ([32P]diC8-PA). CCh increased the accumulation of both [32P]diC8-PA and
      endogenous [32P]phosphatidic acid ([32P]PA) in a time- and dose-dependent manner
      (0.1-100 microM CCh). CCh-induced increases in [32P]diC8-PA and [32P]PA were
      inhibited by 1 microM atropine and 3 microM DG kinase inhibitor (R59022). These
      findings indicated the activation of DG kinase by muscarinic receptor stimulation
      in guinea pig taenia coli. Therefore, DG kinase activation may play an important
      role in CCh-induced PA formation. CCh-induced [32P]diC8-PA and [32P]PA
      accumulation was dependent on intracellular calcium concentrations. However, a
      KCl-induced increase in intracellular calcium, without receptor stimulation, was
      ineffective. Moreover, treatment with phorbol ester also increased accumulation
      of both PA species in KCl-treated tissues. These findings suggest that muscarinic
      receptor mediated activation of DG kinase may require both an increase in
      intracellular calcium and PKC activation in guinea pig taenia coli.

PMID- 7802690
TI  - Evaluation of estrogen receptor, antiestrogen binding sites and calmodulin for
      antiestrogen resistance of two clones derived from the MCF-7 breast cancer cell
      line.
AB  - Estrogen receptor (ER), antiestrogen binding sites (AEBS) and calmodulin (CaM)
      are potential targets of antiestrogen (AE) action. To analyse further which of
      these targets are primarily involved in the antiproliferative activity of these
      drugs against human breast cancers, two cell clones, namely the RTx6 and LY-2
      variants, selected from MCF-7 cells for their resistance to high doses of
      tamoxifen (TAM) and the Keoxifen (KEO) analog LY 117018, respectively, were
      studied for their sensitivity to hydroxytamoxifen (OH-TAM) and KEO as well as the
      strong calmodulin antagonist calmidazolium. The effects of these drugs on both
      cell growth and progesterone receptor (PgR) concentration were assessed. Binding
      properties for ER, AEBS and CaM of each compound were also measured. Our results
      confirmed that basal growth of RTx6 and LY-2 cells was more resistant to OH-TAM
      and KEO than parent MCF-7 cells, although both displayed a significant inhibition
      at the highest doses assessed. In regard to calmidazolium inhibition, each
      variant behaved as did the MCF-7 line indicating that a modification at the CaM
      level was not responsible for their lower sensitivity to AEs. Nor could the
      association of CaM to ER which did not differ among all cell lines. Resistance of
      these variants was not related to AEBS in view of the total lack of such sites in
      RTx6 cells. However, under estrogenic growth stimulation such sites may play some
      role, since LY-2 cells in the presence of estradiol displayed a real antiestrogen
      resistant pattern while RTx6 cells were more sensitive than MCF-7 cells to OH
      TAM. This property was not found in the antagonism against estradiol-induced PgR
      synthesis which was observed with each variant. Thus the PgR concentration of
      RTx6 cells was strongly down-regulated by OH-TAM and KEO and reduced in LY-2
      cells to the same extent as in MCF-7 cells. All these observations show that AE
      resistance is not entirely related to ER mediated events and that alterations at
      the ER and CaM levels are unlikely to account for the lower AE sensitivity of the
      variants investigated.

PMID- 7802691
TI  - Propentofylline enhancement of the actions of adenosine on neutrophil leukocytes.
AB  - In agreement with previous results, activation of adenosine A2 receptors was
      found to inhibit the exocytotic release of elastase and the oxidative burst
      induced by formyl-MetLeuPhe (fMLP) in human neutrophils. The adenosine analogue
      5'-N-ethylcarboxamidoadenosine (NECA) was more potent than adenosine (IC50 14 vs
      64 nM). The effects of adenosine and NECA were not influenced by the A1-adenosine
      receptor selective antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX; 300 nM),
      but were abolished by the non-selective adenosine receptor antagonist 9-chloro-2
      (2-furanyl)-5,6-dihydro-[1,2,4]-triazolo[1,5]quinazolin -5-imine
      monomethanesulfonate (CGS 15943; 10 microM). Propentofylline per se caused a
      concentration-dependent inhibition of H2O2 production. At 100 microM
      propentofylline significantly enhanced the effect of adenosine, but not that of
      NECA. This effect of propentofylline was shared by the known uptake inhibitor
      dipyridamole. Neither adenosine nor propentofylline altered fMLP-induced inositol
      (1,4,5)-trisphosphate (IP3) formation. The results demonstrate that
      propentofylline can counteract neutrophil activation, at least partly by
      enhancing the action of adenosine through blocking its removal, and that the
      effect is exerted at a step after the initial receptor events.

PMID- 7802692
TI  - Apparent hydroxyl radical generation without transition metal catalysis and
      tyrosine nitration during oxidation of the anti-tubercular drug, isonicotinic
      acid hydrazide.
AB  - Aromatic hydroxylation and formation of thiobarbituric acid-reactive substances
      occurred in a mixture of isonicotinic acid hydrazide (isoniazid) and catalase.
      Since these reactions were stimulated by phytic acid (a potent metal chelator),
      rather than inhibited, transition metal-catalysed hydroxyl radical generation was
      not implicated. Hydroxylation also occurred with isoniazid and phytic acid in the
      absence of catalase, albeit to a lesser extent. The independent effects of
      catalase and phytic acid are related to their abilities to catalyse isoniazid
      oxidation. In the presence of tyrosine, both the isoniazid/phytic acid system and
      authentic peroxynitrite generated dityrosine. Authentic peroxynitrite, as well as
      a phytic acid-mediated isoniazid oxidation product, have absorbance maxima at 302
      nm. The yield of this isoniazid-derived product increased with pH and in the
      presence of a superoxide-generating system. A good correlation existed between
      absorbance at 302 nm and aromatic hydroxylation. Acid-induced decomposition of
      the 302 nm absorbance in the presence of superoxide dismutase led to the
      formation of a product absorbing in the same region as peroxynitrite-modified
      superoxide dismutase (350 nm at acid pH). Catalase catalysed peroxynitrite
      mediated, as well as isoniazid/phytic acid-mediated tyrosine nitration, which was
      accompanied by Compound II formation (ferryl-catalase) in both cases. We
      postulate that peroxynitrite or a similar species is formed during isoniazid
      oxidation.

PMID- 7802693
TI  - A2a/D2 receptor interactions are not observed in COS-7 cells transiently
      transfected with dopamine D2 and adenosine A2a receptor cDNA.
AB  - The rat D2 receptor and the dog A2a receptor subcloned into the pXM vector were
      transiently transfected into COS-7 cells using the DEAE-dextran method. The
      transfected cells expressed approx. 200 fmol D2 receptors/mg protein and approx.
      5 pmol/mg protein of the A2a receptor as judged by binding experiments with
      [3H]raclopride [or[3H]-N-propyl-apomorphine (NPA)] and [3H]-CGS 21680,
      respectively. The high affinity KD values were 0.43 and 19 nM for D2 and A2a
      receptors, respectively, in agreement with results obtained from other cells and
      tissues. The non-selective adenosine receptor agonist NECA stimulated cAMP
      accumulation both in non-transfected and transfected COS-7 cells with only a
      slight difference in potency, suggesting that most of the stimulation is due to
      activation of A2b receptors known to be present on virtually every cell. The two
      A2a selective agonists CGS 21680 and CV-1808 were essentially inactive in
      transfected COS-7 cells, but were very active in PC-12 cells known to possess
      functional A2a receptors. Dopamine did not decrease cAMP accumulation in the
      transfected COS-7 cells. CGS 21680 (30 nM) did not affect the binding
      characteristics of D2 receptors in the co-transfected COS-7 cells in contrast to
      the increased KH, KL and RH values found previously in rat striatal membranes
      after CGS 21680 treatment. The present findings indicate that transiently
      transfected A2a and D2 receptors in COS-7 cells have normal binding properties,
      but couple poorly to adenylyl cyclase, despite the presence of Gs protein and
      adenylyl cyclase in these cells. Our results also demonstrate that the previously
      reported interactions between A2a receptors and D2 receptors do not occur when
      only the receptor proteins are expressed in COS-7 cells, suggesting that the two
      receptor molecules do not interact directly to influence binding characteristics.

PMID- 7802694
TI  - Specific proton pump inhibitors E3810 and lansoprazole affect the recovery
      process of gastric secretion in rats differently.
AB  - After a single subcutaneous administration (30 mg/kg) of proton pump inhibitor 2
      [(4-(3-methoxypropoxy)-3-methylpyridin-2-yl)-methylsulfiny l]- 1H-benzimidazole
      sodium salt (E3810), or lansoprazole in rats, time courses of inhibitory and
      recovery processes of acid secretion in vivo and pump enzyme activity in isolated
      microsomes were measured. The acid secretion rate which reflects H+,K(+)-ATPase
      activity in the secretory canalicular (apical) membrane was compared with that in
      the microsomal fraction which consists mostly of resting, intracellularly-pooled
      tubulovesicles. We found that the canalicular pump was first inhibited, followed
      by slow inhibition of the microsomal pump enzyme activity, with the rate of the
      latter process depending on the inhibitors. It took 2.5 hr for the half-maximal
      inhibition of the microsomal pump in E3810-treated rats, and 6 hr in lansoprazole
      treated rats. The acid secretion and the microsomal enzyme activity completely
      recovered within 48 hr after the administration of E3810, but recovered by only
      20% even 96 hr after the administration of lansoprazole. Incubation with
      dithiothreitol of isolated microsomes obtained from E3810-treated rats
      reactivated the enzyme activity, but not from rats treated with lansoprazole.
      These results suggest that dissociation of inhibitor from the pump and/or
      intracellular transport of the pump is affected differently by these inhibitors.
      Furthermore, it is possible that the half life of the proton pump protein is much
      longer (greater than 96 hr) than the previously proposed value of 30-48 hr.

PMID- 7802695
TI  - Effect of 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7) on HSP70 and HSP28
      gene expression and thermotolerance development in human colon carcinoma cells.
AB  - The effect of 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7), a potent
      protein kinase C (PKC) inhibitor, on the development of thermotolerance and
      expression of heat shock genes (HSP70 and HSP28) was investigated in human colon
      carcinoma HT-29 cells. After acute heating at 45 degrees for 15 min, cells became
      resistant to a challenge heat shock. The development of thermotolerance was
      suppressed by adding H-7 after heat shock. Northern blots show that the levels of
      HSP70 and HSP28 mRNA increased rapidly and reached maximal values within 6 hr. H
      7 suppressed the accumulation of HSP70 and HSP28 mRNA as well as their protein
      synthesis, and the level of suppression was concentration dependent. However,
      little effect was observed if the drug was added 1 hr before and during heat
      shock. These results suggest that PKC is involved in the regulation of heat shock
      gene expression after acute heat shock.

PMID- 7802696
TI  - Modulation of endothelin-1 production by a pulmonary epithelial cell line. I.
      Regulation by glucocorticoids.
AB  - Endothelin-1 (ET-1) is one of the most potent bronchoconstrictor agents yet
      described. Bronchial epithelial cells of asthmatic patients in vivo express
      preproET-1 and in vitro release high amounts of ET-1. Healthy and chronic
      bronchitic controls do not express preproET-1 or release ET-1. Interleukin-2 (IL
      2) and other cytokines up-regulate the in vitro ET-1 release in guinea pig airway
      epithelial cells. We explored whether two glucocorticoids, dexamethasone (Dex)
      and triamcinolone acetonide (TA), inhibit the synthesis and release of ET-1 by
      A549 cells, a transformed human pulmonary epithelial cell line, since ET-1 may
      have a basic role in the pathogenesis of asthma. Cells were grown to confluence
      in RPMI 1640 plus 10% fetal bovine serum (FBS). Cells were then cultured for 3
      days without serum to obtain ET-1 basal levels. The effects of 10% FBS, IL-2 (10
      U/mL), Dex, TA or mifepristone, a steroid antagonist (1, 10 or 100 nM), were
      evaluated on ET-1 as measured by radioimmunoassay (RIA). ET-1 production
      increased from 57.6 +/- 5 pg/mg cell protein at 6 hr to 170 +/- 9 pg/mg cell
      protein at 72 hr in control cultures. Ten percent FBS increased ET-1 production
      from 58.7 +/- 9.6 to 399 +/- 14.5 pg/mg cell protein. IL-2 significantly
      increased ET-1 from 100.7 +/- 6.1 to 144 +/- 6.7 at 24 hr and from 170 +/- 9 to
      207.7 +/- 24 at 72 hr. Dex and TA (10 and 100 nM) at 24-72 hr decreased ET-1
      under basal conditions. Both drugs (only at 100 nM) decreased ET-1 production in
      10% FBS- and IL-2-stimulated cells. Mifepristone (10 and 100 nM) reversed the
      decreased production of ET-1 induced by Dex (100 nM) at 24-72 hr. Northern blot
      analysis showed that Dex (100 nM) decreased the expression of ET-1 mRNA at 6 and
      24 hr, but that mifepristone (100 nM) reversed this effect in cells cultured with
      Dex. In conclusion, Dex and TA down-regulate the synthesis and production of ET-1
      by this human pulmonary epithelial cell line under basal or stimulated
      conditions, and these effects are reversed by mifepristone. These findings
      suggest a novel mechanism of glucocorticoid effect during the treatment of
      asthma.

PMID- 7802697
TI  - Characterization of high-affinity binding sites for diisopropylfluorophosphate
      (DFP) from chicken spinal cord membranes.
AB  - The delayed neurotoxic organophosphate [3H]diisopropylfluorophosphate ([3H]DFP)
      binds with high affinity to membrane-bound proteins from the chicken spinal cord.
      The DFP binding proteins were solubilized from membrane preparations, using a
      detergent (CHAPS). The protein(s) sites that labeled with a low concentration of
      [3H]DFP, e.g. 10(-10)-10(-9) M, were defined as the high-affinity binding sites.
      The density (or concentration) of the high-affinity binding sites in protein(s)
      was determined by the difference between total and non-specific binding. The high
      affinity binding sites were saturable, and the maximal amount of binding sites
      was estimated at 400 fmol/mg protein. [3H]DFP binding to solubilized proteins was
      not completely reversible. Concentration-dependent curves suggested that the
      [3H]DFP binding sites differ from the active sites of acetylcholinesterase,
      butyrylcholinesterase, and neuropathy target esterase, as well as from muscarinic
      acetylcholine receptors. The amount of DFP binding sites after a neurotoxic dose
      of tri-o-cresyl phosphate (TOCP) decreased markedly in membrane preparations from
      the chicken spinal cord. These results indicate that a TOCP metabolite(s)
      interacts with the DFP binding sites in vivo. Gel filtration chromatography of
      the solubilized membranes indicated at least two major high-affinity DFP binding
      proteins with apparent molecular weights of 300 and 110 kDa. The DFP binding
      sites corresponding to the 110 kDa protein were insensitive to eserine, a potent
      anti-cholinesterase agent.

PMID- 7802698
TI  - Induction of vitamin D 24-hydroxylase messenger RNA and activity by 22
      oxacalcitriol in mouse kidney and duodenum. Possible role in decrease of plasma 1
      alpha,25-dihydroxyvitamin D3.
AB  - The synthetic analog of 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3], 22
      oxacalcitriol (OCT), retains most of the properties of 1,25(OH)2D3 but exhibits
      much less hypercalcemic action than the parent compound. The effects of OCT on
      plasma calcium, phosphorus, and 1 alpha,25-dihydroxyvitamin D [1,25(OH)2D]
      concentrations were examined in mice. Administration of a single dose (24 pmol/g
      body wt, i.p.) of OCT had no effect on plasma calcium for up to 48 hr,
      significantly increased plasma phosphorus at 4 and 8 hr and significantly reduced
      the concentration of 1,25(OH)2D in plasma between 4 and 48 hr. Both OCT and
      1,25(OH)2D3 at 24 pmol/g body wt (i.p.) induced a single, 3.4-kb mRNA encoding
      vitamin D 24-hydroxylase (24-OHase), the cytochrome P450 enzyme responsible for
      1,25(OH)2D3 degradation, in kidney and duodenum. The OCT-induced increase in 24
      OHase mRNA and an increase in enzyme activity were marked at 2 and 4 hr in both
      tissues. In kidney, mRNA abundance had decreased by 8 hr but remained above basal
      values for up to 30 hr; activity remained relatively high for up to 48 hr. In
      duodenum, 24-OHase mRNA abundance returned virtually to control values by 8 hr
      after OCT treatment; activity remained at nearly maximal levels for up to 30 hr
      but was decreased at 48 hr. The effects of OCT and 1,25(OH)2D3 on 24-OHase mRNA
      abundance and enzyme activity were dose-dependent in kidney and duodenum. Whereas
      the dose-response relations for the effects of both compounds on 24-OHase mRNA
      were similar, OCT was slightly more potent than 1,25(OH)2D3 in stimulating 24
      OHase activity in both tissues. These results suggest that the OCT-induced
      decrease in plasma 1,25(OH)2D3 is attributable, at least in part, to an increased
      degradation of 1,25(OH)2D3, which results from an increase in 24-OHase abundance
      and enzyme activity.

PMID- 7802699
TI  - Role of adenosine A1 receptors in inhibition of receptor-stimulated cyclic AMP
      production by ethanol in hepatocytes.
AB  - Brief exposure of primary cultures of hepatocytes to ethanol had a biphasic
      effect on glucagon receptor-dependent cyclic AMP (cAMP) production: 25-50 mM
      ethanol decreased cAMP levels, whereas treatment with 100-200 mM ethanol
      increased cAMP. This biphasic effect was also observed after pretreatment with 10
      microM 4-methylpyrazole, an inhibitor of alcohol dehydrogenase. Adenosine A1 and
      A2 receptors in primary cultures of rat hepatocytes are coupled to inhibition and
      stimulation of adenylyl cyclase, respectively. Since primary cultures of
      hepatocytes release adenosine into their extracellular media, we tested whether
      the acute effects of ethanol on cAMP were mediated by extracellular adenosine. Co
      incubation with 2 U/mL adenosine deaminase prevented inhibition of cAMP
      production by 25-50 mM ethanol, but had no effect on stimulation by 100-200 mM
      ethanol. Pretreatment of hepatocytes with 110 nM 8-cyclopentyl-1,3
      dimethylxanthine, an adenosine A1 receptor antagonist, also completely blocked
      the inhibitory effects of ethanol on cAMP production. Low concentrations of
      ethanol enhanced the inhibitory effects of R(-)N6-(2-phenylisopropyl)adenosine,
      an A1 receptor agonist, on cAMP production in cells pretreated with adenosine
      deaminase to remove endogenous adenosine. These data suggest that endogenously
      produced adenosine can be an important modulator of the effects of ethanol on
      receptor-stimulated cAMP production in primary cultures of rat hepatocytes.

PMID- 7802700
TI  - Interaction of sanguinarine iminium and alkanolamine form with calf thymus DNA.
AB  - The interaction of sanguinarine iminium form (structure I) and sanguinarine
      alkanolamine form (structure II) with calf thymus DNA has been studied in buffer
      of pH 5.2 and pH 10.5, respectively, where the physicochemical properties of DNA
      remain unchanged. The binding of sanguinarine iminium form to DNA is
      characterized by hypochromism and bathochromism in the absorption band, quenching
      of fluorescence intensity, increase in fluorescence polarization anisotropy,
      increase in positive and negative ellipticity of DNA, sign and magnitude of the
      thermodynamic parameters and increase in contour length of sonicated rodlike
      duplex DNA indicating that it binds to DNA by a mechanism of intercalation. In
      contrast, sanguinarine alkanolamine form does not show (i) any significant change
      in fluorescence polarization anisotropy, (ii) alteration of B form structure of
      DNA and (iii) increase in contour length of DNA indicating that it does not bind
      to DNA. But at a very high concentration of DNA, the alkanolamine form is
      influenced to form an iminium-DNA complex.

PMID- 7802701
TI  - Reduction of fatty acid ethyl ester accumulation by ganglioside GM1 in rat fetus
      exposed to ethanol.
AB  - The biochemical mechanism of alcohol teratogenicity is not known. We have
      demonstrated that alcohol administration to pregnant rats during gestation days
      (GD) 6 and 7 and/or 13 and 14 leads to significant accumulation of ethyl esters
      of long chain fatty acids (FAEEs) in both maternal and fetal organs. This
      observation extends the report of Bearer et al. (Pediat Res 31: 492-495, 1992)
      who detected the presence of metabolites in maternal and fetal organs of pregnant
      C57B1/6J mice exposed to alcohol on GD 7 and/or GD 14. The ethyl esters of
      arachidonic, linoleic, oleic, stearic and palmitic acids were major metabolites
      detected in both maternal and fetal organs. It was also demonstrated that
      detectable levels of FAEEs remain 14 days (GD 20) after initial exposure to
      alcohol on GD 7. Ganglioside GM1 treatment 1 and 24 hr prior to alcohol exposure
      on both GD 7 and/or GD 14 reduced the accumulation of FAEEs. A similar regimen
      was shown to prevent development of tolerance to alcohol in the adult pups
      exposed to alcohol in utero in our previous studies. Thus, the ganglioside GM1
      may have therapeutic value in reducing neurobehavioral effects of alcohol
      exposure in utero.

PMID- 7802702
TI  - Tissue pharmacokinetics of 2',3'-dideoxyinosine in rats.
AB  - The present study examined in rats the concentration-time profiles of 2',3'
      dideoxyinosine (ddI) in pharmacologically relevant tissues, including organs
      where drug effects are desired (brain, lymph nodes, spleen), organs with known
      drug toxicity (pancreas), and major eliminating organs (liver, kidney). ddI was
      analyzed by high performance liquid chromatography and radioimmunoassay. In the
      liver, pancreas, spleen, brain and lymph nodes, the highest concentrations were
      reached between 4 and 7 min after drug administration. The concentrations
      subsequently declined in parallel with those in plasma, indicating that plasma
      and these tissues were in rapid equilibrium. The concentrations in these tissues
      were less or equal to that of plasma. In the kidney, the maximal concentration
      occurred at a later time of 14 min, after which concentrations also declined in
      parallel to those in plasma. The kidney concentrations were about 10-fold greater
      than plasma concentrations. The ratios of tissue-to-plasma concentrations and of
      areas under the tissue and plasma concentration-time profiles showed a 230- to
      300-fold range with the rank order of kidney >> liver approximately pancreas >
      lymph nodes > spleen >> brain, with respective values of 10.4, 1.09, 0.90, 0.75,
      0.42, and 0.04. These data indicate no accumulation of ddI in brain, lymph nodes,
      spleen, pancreas and liver, and a significant accumulation in the kidney. The low
      tissue-to-plasma ratios in brain and spleen and a moderate ratio in lymph nodes
      indicate that further enhancement of the therapeutic effect of ddI requires
      improved drug delivery and entrapment in these tissues.

PMID- 7802703
TI  - Anti-neoplastic activity of sequenced administration of O6-benzylguanine,
      streptozotocin, and 1,3-bis(2-chloroethyl)-1-nitrosourea in vitro and in vivo.
AB  - The purpose of this study was to evaluate the anti-tumor activity of sequenced
      administration of O6-benzylguanine (BG), streptozotocin (STZ), and 1,3-bis(2
      chloroethyl)-1- nitrosourea (BCNU) in vitro and in vivo. We measured the recovery
      of O6-methylguanine DNA methyltransferase (MGMT) and BCNU cytotoxicity in the
      human glioma SF767 cell line, and anti-tumor activity against xenografts
      following exposure to BG, STZ or the combination of BG + STZ combined with BCNU.
      In SF767 cells, the combination of BG (10 microM) + STZ (0.05 mM) produced
      sustained inhibition of MGMT activity for at least 24 hr, and a greater
      potentiation of BCNU cytotoxicity than either agent alone. The combined treatment
      of BG + STZ increased BCNU-induced cell kill by 0.5 to 1.0 log over BG or STZ
      alone. The maximally tolerated doses of the combination of BG + STZ + BCNU
      administered to nude mice i.p. were the following: BG (80 mg/kg), STZ (100
      mg/kg), and BCNU (15 mg/kg). Utilizing these doses of BG and STZ, the depletion
      and repletion profile of MGMT activity in SF767 xenografts was measured. STZ at
      100 mg/kg did not affect xenograft MGMT activity. Subsequent to BG treatment,
      xenograft MGMT activity was inactivated completely for 12 hr, and the tumors
      gradually recovered approximately 40% of control activity by 24 hr. The
      combination of BG + STZ produced sustained inhibition of MGMT activity for 24 hr
      in the xenografts with complete recovery of MGMT activity by 48 hr.
      Administration of the combination of BG + BCNU to nude mice bearing SF767 tumor
      resulted in significant inhibition of tumor growth for 23 days. However, the
      addition of STZ to this combination provided no greater anti-tumor activity than
      that observed with BG + BCNU. The three-drug combination of BG, STZ, and BCNU
      produced no more than 2.4 to 13.0% weight loss with occasional lethal toxicity.
      Collectively, these data suggest that prolonged depletion of MGMT might be
      required for optimal reversal of BCNU resistance both in vitro and in vivo.

PMID- 7802704
TI  - Purine substrates for human thiopurine methyltransferase.
AB  - Thiopurine methyltransferase (TPMT) catalyzes the S-methylation of thiopurine
      drugs such as 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG). A genetic
      polymorphism regulating TPMT activity in human tissue is an important factor
      responsible for individual differences in the toxicity and therapeutic efficacy
      of these drugs. Because of the clinical importance of this polymorphism, we
      studied 18 purine derivatives, including ribonucleosides and ribonucleotides, as
      potential substrates for purified human kidney TPMT. Sixteen of the compounds
      studied were substrates for the enzyme, with Km values that varied from 29.1 to
      1270 microM and with Vmax values that varied from 75 to 2340 U/mg protein. The
      thiopurines tested had Km values that were uniformly lower than were those of the
      corresponding ribonucleosides or ribonucleotides. 6-Selenopurine derivatives had
      the lowest Km values of the compounds studied. Finally, oxidized purines with an
      OH in the 8-position were methylated by the enzyme, but 2-OH compounds were
      potent inhibitors of TPMT.

PMID- 7802705
TI  - Dnacin A1 and dnacin B1 are antitumor antibiotics that inhibit cdc25B phosphatase
      activity.
AB  - The p80cdc25 protein is a protein phosphatase directly involved in p34cdc2
      protein kinase activation by dephosphorylation. The cdc25B gene is one of three
      human cdc25 homologs which can complement the temperature-sensitive cdc25
      mutation of Schizosaccharomyces pombe, and is expressed a high levels in human
      cell lines, particularly in some cancer cells. A fusion protein of glutathione-S
      transferase (GST) and the catalytic domain of cdc25B protein was constructed and
      found to retain phosphatase activity in the manner of a p80cdc25 phosphatase by
      using a chromogenic substrate, p-nitrophenylphosphate. Two benzoquinoid antitumor
      compounds, dnacin A1 and dnacin B1, inhibited phosphatase activity in a non
      competitive manner.

PMID- 7802706
TI  - Frequency-dependent alterations in enolase activity in Escherichia coli caused by
      exposure to electric and magnetic fields.
AB  - Some neurochemical effects of low-intensity electric and magnetic fields have
      been shown to be nonlinear functions of exposure parameters. These effects
      occurred within narrow ranges of frequency and intensity. Previous studies on
      membrane-associated endpoints in cell culture preparations demonstrated changes
      in calcium efflux and in acetylcholinesterase activity following exposure to
      radiofrequency radiation, amplitude modulated (AM) at 16 and at 60 Hz, at a
      specific absorption rate of 0.05 W/kg. In this study, these modulation
      frequencies were tested for their influence on the activity of a cytoplasmic
      enzyme, enolase, which is being tested clinically for detection of neoplasia.
      Escherichia coli cultures containing a plasmid with a mammalian gene for enolase
      were exposed for 30 min, and cell extracts were assayed for enolase activity by
      measuring absorbance at 240 nm. The enolase activity in exposed cultures was
      compared to the activity in paired control cultures. Exposure to 147 MHz carrier
      waves at 0.05 W/kg, AM at 16 Hz showed enolase activity enhanced by 62%, and AM
      at 60 Hz showed enolase activity reduced by 28%. Similarly, exposure to 16 Hz
      fields alone, at 21.2 V/mrms (electric) and 97 nTrms (magnetic), showed
      enhancement in enolase activity by 59%, whereas exposure to 60 Hz fields alone,
      at 14.1 V/mrms (electric) and 65 nTrms (magnetic), showed reduction in activity
      by 24%. Sham exposures as well as exposure to continuous-wave 147 MHz radiation
      at 0.05 W/kg showed no change in enolase activity.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7802707
TI  - Chick embryo development can be irreversibly altered by early exposure to weak
      extremely-low-frequency magnetic fields.
AB  - Several reports have shown that weak, extremely-low-frequency (ELF), pulsed
      magnetic fields (PMFs) can adversely affect the early embryonic development of
      the chick. In this study, freshly fertilized chicken eggs were exposed during the
      first 48 h of postlaying incubation to PMFs with 100 Hz repetition rate, 1.0
      microT peak-to-peak amplitude, and 500 microseconds pulse duration. Two different
      pulse waveforms were used, having rise and fall times of 85 microseconds (PMF-A)
      or 2.1 microseconds (PMF-B). It has been reported that, with 2 day exposure,
      these fields significantly increase the proportion of developmental
      abnormalities. In the present study, following exposure, the eggs were allowed to
      incubate for an additional 9 days in the absence of the PMFs. The embryos were
      taken out of the eggs and studied blind. Each of the two PMF-exposed groups
      showed an excess in the percentage of developmental anomalies compared with the
      respective sham-exposed samples. This excess of anomalies was not significant for
      the PMF-A-treated embryos (P = 0.173), whereas it was significant for the PMF-B
      exposed group (P = 0.007), which showed a particularly high rate of early
      embryonic death. These results reveal that PMFs can induce irreversible
      developmental alterations and confirm that the pulse waveform can be a
      determinant factor in the embryonic response to ELF magnetic fields. The data
      also validate previous work based on the study of PMFs' effects at day 2 of
      embryonic development under field exposure.

PMID- 7802708
TI  - Temporally incoherent magnetic fields mitigate the response of biological systems
      to temporally coherent magnetic fields.
AB  - We have previously demonstrated that a weak, extremely-low-frequency magnetic
      field must be coherent for some minimum length of time (approximately 10 s) in
      order to affect the specific activity of ornithine decarboxylase (ODC) in L929
      mouse cells. In this study we explore whether or not the superposition of an
      incoherent (noise) magnetic field can block the bioeffect of a coherent 60 Hz
      magnetic field, since the sum of the two fields is incoherent. An experimental
      test of this idea was conducted using as a biological marker the twofold
      enhancement of ODC activity found in L929 murine cells after exposure to a 60 Hz,
      10 microT rms magnetic field. We superimposed an incoherent magnetic noise field,
      containing frequencies from 30 to 90 Hz, whose rms amplitude was comparable to
      that of the 60 Hz field. Under these conditions the ODC activity observed after
      exposure was equal to control levels. It is concluded that the superposition of
      incoherent magnetic fields can block the enhancement of ODC activity by a
      coherent magnetic field if the strength of the incoherent field is equal to or
      greater than that of the coherent field. When the superimposed, incoherent noise
      field was reduced in strength, the enhancement of ODC activity by the coherent
      field increased. Full ODC enhancement was obtained when the rms value of the
      applied EM noise was less than one-tenth that of the coherent field. These
      results are discussed in relation to the question of cellular detection of weak
      EM fields in the presence of endogenous thermal noise fields.

PMID- 7802709
TI  - Behavioral sensitivity of rats to extremely-low-frequency magnetic fields.
AB  - Work in our laboratory has revealed autonomic and/or behavioral sensitivity of
      mice, rats, and a domestic fowl to extremely-low-frequency (ELF) or nominally
      static magnetic (B) fields at flux densities between 250 and 1700 microT (rms).
      To extend our work, an automated exposure and data-acquisition system was used
      with the technique of conditional suppression to assess behavioral sensitivity to
      time-varying B fields. Each of five rats was exposed aperiodically to a B field
      during 3 min warning periods that terminated in a brief electric shock. The
      difference between rates of lever pressing during B-field warning periods and
      rates during immediately antecedent, 3 min control periods was analyzed at
      frequencies of 7, 16, 30, 60, and 65.1 Hz. To produce equivalent induced voltages
      in the rat at each frequency, graded flux densities were established that ranged
      from 1900 microT at 7 Hz to 200 microT at 65.1 Hz. Analysis of differences in
      lever-pressing rates revealed that in a given session of testing the rats would
      increasingly suppress responding when exposed to a B field, but this trend was
      independent of frequency. This experiment provides evidence of behavioral
      sensitivity by a mammal to an ELF magnetic field.

PMID- 7802711
TI  - Magnetic-field flux density and spectral characteristics of motor-driven personal
      appliances.
AB  - Flux density and spectral measurements were carried out on magnetic fields
      generated by several types of motor-driven personal appliances used near the
      body. Among the units tested were several for which the average flux densities,
      as determined at the surfaces of the appliance, exceeded 0.4 mT. Time-rates-of
      change (dB/dt) for several units exceeded 1000 T/s, and several units exhibited
      high-frequency components in the low-MHz range. Use of such appliances, although
      normally of short duration, can represent exposure to magnetic fields of
      relatively high flux density, which may also have high-frequency components.
      Compared to other household and commercial sources of magnetic fields, those
      generated by certain motor-driven personal appliances may represent a significant
      contribution to time-weighted average exposure and may represent an important
      source of local induced currents in the body. Furthermore, high-frequency
      transients that represent only a minor contribution to time-weighted average
      exposure may generate significant instantaneous induced currents.

PMID- 7802710
TI  - Electric field exposure alters serum melatonin but not pineal melatonin synthesis
      in male rats.
AB  - Sprague-Dawley male rats, maintained in a 14:10 h light:dark cycle were exposed
      for 30 days (starting at 56 days of age) to a 65 kV/m, 60 Hz electric field or to
      a sham field for 20 h/day beginning at dark onset. Pineal N-acetyltransferase
      (NAT), hydroxy-indole-o-methyl transferase (HIOMT), and melatonin as well as
      serum melatonin were assayed. Preliminary data on unexposed animals indicated
      that samples obtained 4 h into the dark period would reveal either a phase delay
      or depression in circadian melatonin synthesis and secretion. Exposure to
      electric fields for 30 days did not alter the expected nighttime increase in
      pineal NAT, HIOMT, or melatonin. Serum melatonin levels were also increased at
      night, but the electric field-exposed animals had lower levels than the sham
      exposed animals. Concurrent exposure to red light and the electric field or
      exposure to the electric field at a different time of the day-night period did
      not reduce melatonin synthesis. These data do not support the hypothesis that
      chronic electric field exposure reduces pineal melatonin synthesis in young adult
      male rats. However, serum melatonin levels were reduced by electric field
      exposure, suggesting the possibility that degradation or tissue uptake of
      melatonin is stimulated by exposure to electric fields.

PMID- 7802712
TI  - Dose response study of human exposure to 60 Hz electric and magnetic fields.
AB  - This human exposure study examined the relationship between field strength and
      biological response and tested whether the exposure levels at which the greatest
      effects occur differ for different endpoints. Three matched groups of 18 men each
      participated in two 6 h exposure test sessions. All subjects were sham exposed in
      one session. In the other session, each group of subjects was exposed at a
      different level of combined electric and magnetic field strength (low group:6
      kV/m, 10 microT; medium group:9 kV/m, 20 microT; and high group: 12 kV/m, 30
      microT). The study was performed double blind, with exposure order
      counterbalanced. Significant slowing of heart rate, as well as alternations in
      the latency and amplitude of event-related brain potential measures derived from
      the electro encephalogram (EEG), occurred in the group exposed to the 9 kV/m, 20
      microT combined field (medium group). Exposure at the other field strength levels
      had no influence on cardiac measures and differential effects on EEG activity.
      Significant decrements in reaction time and in performance accuracy on a time
      estimation task were observed only in the low group. These results provide
      support for the hypothesis that humans may be more responsive to some
      combinations or levels of field strength than to others and that such differences
      in responsivity may depend, in part, on the endpoint of interest.

PMID- 7802713
TI  - Spreadsheet method for calculating the induced currents in bone-fracture healing
      by a low-frequency magnetic field.
AB  - A commercially available spreadsheet program is used on a microcomputer to
      calculate the induced current density and electric field patterns produced in a
      nonhomogeneous, anisotropic model of tissue by a localized, low-frequency
      magnetic field source. Specific application is made to coils used to promote the
      healing of bone fractures in limbs. The variation of the conductivity of the
      fracture gap during healing causes the induced current density pattern to change
      correspondingly, whereas the induced electric field remains relatively unchanged.
      Use of more simplified, isotropic models for the bone and for the soft tissue
      leads to results that differ significantly from those obtained from the full
      model. The magnetic field beyond the region of the coils contributes little to
      the induced currents in the fracture gap if the gap is located near the center of
      the coils.

PMID- 7802714
TI  - Conductivity differences distort probe measurements of magnetically induced
      electric fields.
AB  - Measuring internal induced electric fields in animals with a miniaturized probe
      involves a potential error related to the difference between the hole
      conductivity (sigma h) and the surrounding tissue conductivity (sigma t). Theory
      was developed to describe this phenomenon and checked by probe measurements in
      agar-filled petri dishes. The value measured in the hole is 2 sigma t/(sigma h +
      sigma t) times the actual field in the tissue. For example, a probe hole in
      muscle, which is filled with blood, could yield a measurement only about 22% of
      the true value in the muscle. This potential source of error can be mitigated to
      some extent by not actually cutting a hole, by using a low-conductivity (e.g.,
      0.2 S/m) coupling medium in the hole, or by ensuring contact between the probe's
      electrodes and the tissue.

PMID- 7802715
TI  - Recovery of nocturnal melatonin concentration takes place within one week
      following cessation of 50 Hz circularly polarized magnetic field exposure for six
      weeks.
AB  - In our earlier paper [Kato et al. (1993): Bioelectromagnetics 14:97-106],
      melatonin concentration in pineal gland and blood was reported to be suppressed
      after exposure to a circularly polarized 50 Hz magnetic field for 6 weeks. In the
      present series of experiments, we investigated the time course of recovery after
      cessation of the exposure. Rats were exposed to a circularly polarized 50 Hz
      magnetic field at 1 microT for 6 weeks, and the melatonin concentration of blood
      of separate groups was determined at the end of the exposure and at 1 week and 4
      weeks following cessation of exposure. Nocturnal melatonin concentration was
      reduced (P < 0.05) after 6 weeks of exposure. Melatonin concentration at 1 week
      following cessation of exposure was normal, and no further change was observed 4
      weeks later.

PMID- 7802716
TI  - Frontiers in Lipid and Lipoprotein Research. Conference proceedings. Atlanta,
      Georgia, 19-21 September 1993.

PMID- 7802717
TI  - Drug and alternative therapies for hyperlipidemia.
AB  - The recent guidelines for detection and treatment of hypercholesterolemia
      together with specific therapeutic goals have stimulated interest in, and use of,
      lipid lowering agents. The last decade has seen an explosive growth in the drug
      discovery area which is now translating into clinical trials with many new lipid
      lowering agents. In addition, clinical trials assessing clinical outcomes and
      cost effectiveness are resulting in a changing approach to how current lipid
      lowering drugs are used, especially in terms of dosing and combination therapies.
      At present only four classes of lipid altering agents remain in wide use; bile
      acid binding resins, niacin, fibrates and HMG CoA reductase inhibitors. Although
      only a decade has passed since the first HMG CoA reductase inhibitor, lovastatin,
      entered clinical trials this group of compounds are not only the most widely used
      lipid lowering agents, but more than six such agents have been or are currently
      being developed. In addition to pharmacological therapies, there have been
      significant advances in the non-pharmacological treatment of
      hypercholesterolemia, the most important being LDL-receptor gene replacement and
      selective LDL-apheresis.

PMID- 7802718
TI  - Preventive cardiology in primary care.
AB  - Primary care physicians play a pivotal role in the successful implementation of
      the National Cholesterol Educational Program (NCEP) guidelines for both
      population and high-risk approaches to reduce blood cholesterol levels in
      children and adults. Increasingly, in this era of health cost containment, the
      primary care physician is recognized as (1) the main and sometimes the only
      source of health care for large numbers of individuals; (2) the affordable
      physician and (3) the gatekeeper for referral to medical specialists. Achievement
      of NCEP guidelines for cholesterol reduction, American Heart Association (AHA)
      guidelines for prevention of cardiovascular disease, and Year 2000 National
      Objectives for Health Promotion and Disease Prevention will all rely heavily on
      the active cooperation and support of practicing internists, pediatricians, and
      family/general practitioners in providing patient education, risk factor
      evaluation and intervention. Although the majority of primary care physicians
      intuitively support the concept of preventive cardiology and generally have a
      high level of knowledge of cardiovascular risk factors, a significant gap remains
      between physician knowledge and attitudes and the actual practice of preventive
      cardiology in clinical practice. Despite these limitations in implementation of
      clinical guidelines, significant progress has been made in the past decade in
      reaching NCEP and Year 2000 goals for population-wide cholesterol reduction.

PMID- 7802719
TI  - Evaluating the effectiveness of dyslipidemia control strategies.
AB  - While cost-effectiveness analyses of anti-hyperlipidemia programs featuring drug
      treatment suggest that the best use of public dollars is to delay treatment until
      an individual develops coronary heart disease, a comprehensive hyperlipidemia
      treatment policy must take a broader perspective. The high case-fatality rates of
      patients exhibiting first manifestations of coronary heart disease, the limited
      population impact of interventions aimed solely at high risk groups, the cost of
      testing to identify the high risk segment of the population, the social origins
      of the behavioral risk factors for coronary heart disease, and the perspective of
      the individual must also be considered. Available data suggest that the best
      public policy to control the burden of heart disease is one with two components:
      On the one hand, all individuals without clinically manifest heart disease would
      be encouraged to adopt healthy behaviors without an attempt to sort the
      population into 'high' and 'not high' risk groups. On the other hand, the risk
      factors of individuals who already have coronary heart disease would be treated
      aggressively with a case-management system of follow-up. The data that support
      this conclusion are presented in this paper.

PMID- 7802720
TI  - Cholesterol and public policy.
AB  - Cholesterol lowering in both primary and secondary prevention has been clearly
      demonstrated to lower coronary morbidity and, in secondary prevention, to lower
      coronary mortality as well. Putative dangers of cholesterol lowering remain
      unproven. Population studies linking low cholesterol to noncoronary mortalities
      do not demonstrate cause-and-effect relations. In fact, based on current studies,
      the opposite is more likely to be the case. Neither gender nor age should
      automatically exclude persons from cholesterol screening. Drug intervention,
      however, should be used conservatively, particularly in young adults and the
      elderly. Drugs should be used only after diet and lifestyle interventions have
      failed. The evidence linking high blood cholesterol to coronary atherosclerosis
      and cholesterol lowering to its prevention is broad-based and definitive.
      Concerns about cholesterol lowering and spontaneously low cholesterols should be
      pursued but should not interfere with the implementation of current public
      policies to reduce the still heavy burden of atherosclerosis in Western society.

PMID- 7802721
TI  - Future in lipid and lipoprotein research: from preventing clinical disease to
      preventing elevated risk factors.
AB  - The decline in cardiovascular disease has been a major public health success. The
      relationship between key risk factors such as blood cholesterol levels, smoking,
      high blood pressure and clinical disease are universally accepted. The approaches
      to the prevention of cardiovascular disease are changing to a greater emphasis on
      the prevention of elevated risk factors by better understanding of the
      relationship between lifestyle and host susceptibility (genetic attributes) and
      the risk factor changes with age. The development of new methods to measure
      vascular disease non-invasively in vivo changes the approaches to evaluation of
      both risk and definition of endpoints in analytical studies and clinical trials.
      It is possible now to increase the rate of decline in coronary heart disease.

PMID- 7802722
TI  - Traditional lipoprotein profile: clinical utility, performance requirement, and
      standardization.
AB  - The lipid and lipoprotein parameters which are predominantly measured and
      effectively comprise the traditional lipoprotein profile include total
      cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein
      (LDL) cholesterol, and triglyceride. Total cholesterol is accepted as the initial
      entry point in a case finding approach such as that recommended by the National
      Cholesterol Education Program (NCEP). HDL cholesterol, known to be a strong
      inverse predicator of risk, is an additional measurement to total cholesterol to
      improve risk assessments. The evidence for triglyceride association remains
      mixed: although strong associations are found in some studies, the evidence as an
      independent risk factor is still incomplete. Triglyceride is therefore measured
      primarily for LDL estimation. Final classification and potential intervention is
      ultimately based on the measurement of LDL cholesterol. Reliability in the
      measurement of total cholesterol, HDL, LDL, and triglyceride is especially
      important if the uniform decision points established by the NCEP are to be
      properly implemented. Attention must be placed on controlling preanalytical
      sources of variation, which can account for as much as 60% of the total
      measurement variability. The major analytical source of error comes from matrix
      effects, which results in problems of proper analytical calibration. Instrument
      system calibration should be verified by a comparison with an accuracy base using
      fresh patient specimens. CDC has established a network of reference method
      laboratories to provide access to these lipid and lipoprotein accuracy bases.

PMID- 7802723
TI  - Capabilities of compact analyzers for decentralized testing of lipids and
      lipoproteins.
AB  - Advances in compact analyzer technology have provided the capability to move
      laboratory testing to the patient, the bedside, the physician office, wellness
      sites and even into the home. The future has arrived in the sense that lipid
      testing can be performed in a simple manner similar to blood pressure testing
      with results immediately available to facilitate treatment decisions. The
      realities of access and utilization as well as the rate of future technology
      developments will be determined to a large degree by government regulatory and
      reimbursement decisions.

PMID- 7802724
TI  - Lipid testing for the year 2000 and beyond.
AB  - Lipid testing has progressed from early measurements of total lipid by extraction
      and weighing to assess the fat content of the specimen. This nonspecific approach
      to lipid testing has been replaced in clinical laboratories by automated and
      quantitative procedures that avoid the extraction process. Instead, selective
      enzymes are utilized in reaction schemes to quantitate the individual lipid
      classes present in patient specimens. For example, cholesterol esterase and
      oxidase are used on a routine basis to measure total cholesterol in plasma and
      serum specimens. Similar use of other enzyme systems has permitted triglycerides
      and phospholipids to be measured by clinical laboratories. Lipid and lipoprotein
      measurements have advanced considerably from the early nonspecific extraction and
      gravimetric analysis schemes to the specific automated procedures that are
      commonly used today. However, as lipids and lipoproteins increased in their
      clinical usefulness as cardiovascular risk assessment tools, the search
      intensified for newer approaches to measure these entities more easily and more
      accurately. The influence of National Cholesterol Education Program has played a
      key role in highlighting the importance of lipids and lipoprotein analysis.
      Today, lipid testing is available outside the traditional laboratory environments
      - drugstores sell units that individuals can use at home to assess cholesterol
      levels. Lipid testing has come a long way, and we have only begun to experience
      some of the remarkable changes for the future.

PMID- 7802725
TI  - Oxidized lipoproteins, altered cell function and atherosclerosis.
AB  - A correlation between atherogenesis and lipoprotein oxidation was first suggested
      by experiments showing increased uptake by macrophages of oxidized LDL and
      oxidized LDL injury to cultured cells. Recent data which demonstrate the
      existence of oxidized lipoproteins in vivo, combined with studies showing a
      'protective' effect of antioxidants against atherosclerosis progression, have
      greatly increased the interest in theories posing that lipoprotein oxidation is
      causally related to arterial disease. The fact that dozens of new compounds are
      produced upon the oxidation of low density lipoprotein has led, perhaps not
      surprisingly, to numerous discoveries in vitro of altered cell function induced
      by exposure of cells to oxidized LDL that are distinct from those resulting from
      exposure to native LDL. This brief overview will describe selected altered cell
      functions of oxidized lipoproteins and how they may impact on atherosclerosis.

PMID- 7802726
TI  - New insights into the pathogenesis of atherosclerosis as revealed by PDAY.
      Pathobiological Determinants of Atherosclerosis in Youth.
AB  - In this progress report the major pathological results gained from the research
      program called The Pathological Determinants of Atherosclerosis in Youth (PDAY)
      are summarized. These results are made possible because of the many unique
      features of this multicenter study, which are also summarized. The following main
      accomplishments utilize special quantitative techniques to study cellular,
      chemical and molecular (genetic) features of the developing plaques in young
      people. These include for the first time: The greater incidence of early
      progressive lesions in selective apo E phenotypes. The greater incidence of
      progressive lesions in black youth with an apo B deletion genotype. The much
      higher concentration of epitopes of oxidized LDL in smokers than non-smokers.
      More prevalent macrophages and lymphocytes in the standardized thoracic aortic
      samples, where lesions progress slowly, than in the abdominal aortic core
      samples, where lesions are much more likely to become severe. A strong
      correlation between the mast cell population and the concentration of biogenic
      amines in the lesions. The location of Lp(a) specific antigens in these
      developing lesions as compared to apo B. The accumulation of extracellular lipid
      where progression of lesions is most rapid, with special emphasis on the effects
      of smoking. The correlation of modulation of the intimal smooth muscle cells with
      the sites where progression of the plaque is most frequent. Preliminary
      ultrastructural evidence of intimal platelet and leukocyte adherence and entrance
      into the intima of the thoracic aorta, where there is likely to be lack of
      progression of lesions. A review of the recently published biochemical evidence
      of the correlation of increased lesion cholesterol and collagen content in the
      abdominal aorta. The continuing studies and their implications are also
      summarized.

PMID- 7802727
TI  - Fibrinolytic and thrombotic factors in atherosclerosis and IHD: the influence of
      triglyceride rich lipoproteins (TGRLP).
AB  - TGRLP interactions with the endothelium may increase the likelihood that a
      suppressed fibrinolytic capacity and/or an increased procoagulant activity
      enhances the risk for an ischemic event, that is, for the production of a focal
      thrombus. The cellular mechanisms and characteristics of TGRLP in hyperlipemia
      and in the postprandial state that contribute to their potential pathology in IHD
      are considered.

PMID- 7802728
TI  - Familial lipoprotein disorders and premature coronary artery disease.
AB  - Significant risk factors for premature coronary heart disease include: (1) family
      history, (2) elevated low density lipoprotein (LDL) cholesterol level > or = 160
      mg/dl, l, (3) decreased high density lipoprotein (HDL) cholesterol level < 35
      mg/dl, l, (4) cigarette smoking, (5) high blood pressure and (6) diabetes
      mellitus. All of these risk factors are common in patients with premature heart
      disease. Common familial lipid disorders associated with premature heart disease
      include familial lipoprotein(a) excess, familial dyslipidemia (elevated
      triglycerides and decreased HDL cholesterol), familial combined hyperlipidemia
      (elevations of LDL cholesterol and triglycerides, and often decreased HDL
      cholesterol), familial hypoapobetalipoproteinemia (elevated apolipoprotein B
      levels), familial hypoalphalipoproteinemia (low HDL cholesterol levels), and
      familial hypercholesterolemia (elevated LDL cholesterol levels). All these
      disorders have been characterized using age and gender specific 90th and 10th
      percentile values from the normal population. The diagnosis and potential
      management of these disorders is reviewed.

PMID- 7802729
TI  - Dyslipoproteinemia and other risk factors for atherosclerosis in children and
      adolescents.
AB  - The early lesions of atherosclerosis in youth are strongly related to antemortem
      levels of total and low density lipoprotein (LDL) cholesterol, very low density
      lipoprotein (VLDL) cholesterol, and triglyceride, to ponderal index and to
      systolic and diastolic blood pressure. The major apolipoproteins of LDL and high
      density lipoprotein (HDL), apo B and apo A1, respectively, as well as levels of
      Lp(a) lipoprotein are often abnormal in children born to a parent with coronary
      artery disease (CAD). Other risk factors for CAD include obesity, high blood
      pressure, cigarette smoking, diabetes mellitus, positive family history of CAD
      and physical inactivity. Children from families with premature CAD, familial
      dyslipidemia or hypertension, and/or two other risk factors should have a
      lipoprotein profile determined. The first form of treatment is a diet low in
      total fat, saturated fat and cholesterol, combined with treatment of
      overnutrition and obesity, if necessary, and regular habits of aerobic physical
      activity. Children with inherited disorders of LDL metabolism may require the
      addition of lipid lowering therapy. The early detection and treatment of youth at
      risk for premature CAD offers the greatest promise to decrease morbidity and
      mortality.

PMID- 7802730
TI  - Lipids, lipoproteins, women and cardiovascular disease.
AB  - The risk factors for cardiovascular disease are related directly or indirectly in
      women, as in men, to lipid and lipoprotein levels. But women have the advantage
      of the beneficial effects of either endogenous or exogenous estrogen on these
      levels throughout most of their lives. Behaviors such as smoking or diseases such
      as diabetes interfere with the favorable lipid and lipoprotein levels seen in
      women, and heart disease risk is increased significantly. Oral contraceptives
      have negative effects on lipids but appear not to increase risk for
      atherosclerosis in current or past users. Postmenopausal estrogen therapy appears
      to protect women from heart disease, but the long-term effect on risk is unknown
      for combination hormone therapy. The monitoring of a women's lipid profile, a
      major indicator of risk for heart disease, is of paramount importance.

PMID- 7802731
TI  - Lipids, lipoproteins and coronary heart disease in minority populations.
AB  - Despite recent advances in both prevention and treatment, cardiovascular disease
      (CVD) remains the leading cause of mortality in the US. The Framingham Study was
      a landmark in defining CHD-related risk factors; unfortunately, very few
      minorities were included. A major preventable risk factor for CHD continues to be
      lipid abnormalities, but its association within minority populations is unclear.
      The few studies that have examined the association of hyperlipidemia with CHD in
      minorities have shown that total cholesterol was a predictor of CHD risk (e.g.,
      black men aged 35-64). Several researchers have reported higher levels of HDL for
      black men and women compared to white men and women. Since HDL was shown to be
      inversely related to CHD, this discrepancy in HDL is hypothesized to account for
      the lower than expected mortality rate. Lipoprotein(a) has been identified as an
      independent risk factor for CHD; blacks have considerably higher levels than
      whites. Data also indicate the following: Hispanics have lower CVD mortality
      rates than the general population despite having known risk factors (e.g.,
      obesity, diabetes, low socioeconomic status); Hispanic women have lower levels of
      HDL cholesterol; Native-American populations have lower prevalence of CHD
      associated with lower LDL-cholesterol and higher HDL-cholesterol. Understanding
      epidemiologic and pathophysiologic data regarding differences between various
      racial groups should help reduce CVD-related morbidity and mortality in minority
      populations.

PMID- 7802732
TI  - Screening for lung cancer re-examined. A reinterpretation of the Mayo Lung
      Project randomized trial on lung cancer screening.
AB  - In the 1970s, three randomized trials, each involving approximately 10,000 male
      subjects, were carried out to determine the value of lung cancer screening in
      cigarette smokers. These studies have been widely interpreted as providing strong
      evidence that screening does not contribute to decreased death rates, and,
      accordingly, the American Cancer Society firmly recommends against lung cancer
      screening. No randomized trial, however, has evaluated screening for lung cancer
      in women, who currently comprise 39% of the lung cancer population. The trials
      performed at Memorial-Sloan Kettering and at Johns Hopkins were designed so that
      subjects were randomized to either a single screen (annual chest x-ray alone) or
      a dual screen (annual chest x-ray and every-4-month sputum cytology) group. While
      the results of both revealed no difference in mortality between the groups, these
      studies were designed to examine the value of sputum cytology, and no conclusion
      regarding the efficacy of chest x-rays can be inferred. In the Mayo Lung Project,
      patients were randomized to a screened group in which a chest x-ray and sputum
      cytology were obtained every 4 months or to a control group in which an annual
      chest x-ray and cytology were simply recommended. The results indicate that after
      6 years, more lung cancers were detected among the 4,618 men in the screened
      group (206 cases, 4.46%) than in the 4,593 men in the control group (160 cases,
      3.48%). The screened group showed a superiority over the control subjects in
      resectability rate (46% vs 32%) and 5-year survival (33% vs 15%). However, the
      number of cancer deaths was slightly greater in the screened (122) than in the
      control group (115), and, consequently, the mortality rates were not
      significantly different among the groups. An "overdiagnosis bias" has been
      suggested to account for the increased number of lung cancers detected in the
      screened vs the control population in the Mayo Lung Project. This explanation is
      statistically plausible, but, given the status of lung cancer as the most lethal
      of malignancies, is biologically unlikely. An alternative hypothesis is that
      chance alone might have accounted for the observed 0.98% difference in lung
      cancer detection rates. Were this the case, then 46 additional cases would have
      been detected in the control group had this chance event not occurred.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7802733
TI  - The effect of early separation from the mother on pups in bonding to humans and
      pup health.
AB  - The separation of young dogs from their mother at the age of 6 weeks had a
      negative effect on the physical condition and weight gain of separated pups
      compared to that of pups with maternal contact till 12 weeks. Disease
      susceptibility and mortality was higher in pups with a shorter maternal contact
      period. These factors were related to behavioural measurements of separation
      stress. However, early separation had no significant advantage to socialisation
      with humans, provided that separated and nonseparated pups had daily human
      contact. Early separation therefore did not improve dog/human bonding processes
      but lowered condition and increased mortality in separated pups.

PMID- 7802734
TI  - The history of the condom.

PMID- 7802735
TI  - Asthma and asthma-like symptoms in adults assessed by questionnaires. A
      literature review.
AB  - The first widely used questionnaire in respiratory epidemiology was the
      questionnaire from the Medical Research Council (MRC) of Great Britain. In the
      first version, from 1960, there were only a few questions about wheezing, but in
      later editions, more questions about asthma and asthma-like symptoms were added.
      The MRC questionnaire initiated the development of other questionnaires such as
      the European Community for Coal and Steel (ECSC) questionnaire of respiratory
      symptoms and the questionnaire from the American Thoracic Society and the
      Division of Lung Diseases (ATS-DLD-78). In Tucson, Ariz, a questionnaire was
      developed in the 1970s that was focused on the subject's own report of asthma. In
      Great Britain, a questionnaire was developed in the 1980s with the intention of
      finding the most valid symptom-based items for identifying asthma, "the IUATLD
      (1984) questionnaire." When judging the validity of a questionnaire, it is
      essential to understand sensitivity and specificity. Sensitivity is the fraction
      of the truly diseased subjects found to be diseased using the questionnaire.
      Specificity is the fraction of the truly healthy subjects found to be healthy
      using the questionnaire. Regarding questionnaires dealing with asthma, the
      situation is confusing because of the absence of any gold standard for asthma.
      The most usual mode of validation has been to test the questionnaire against the
      results of a clinical physiologic investigation, often a nonspecific bronchial
      challenge test. Another approach has been to compare the answers from the
      questionnaire with the clinical diagnoses of asthma. When validated in relation
      to bronchial challenge tests, the questions about self-reported asthma have a
      mean sensitivity of 36 percent (range, 7 to 80 percent) and a mean specificity of
      94 percent (range, 74 to 100 percent). The questions about "physician-diagnosed
      asthma" have even higher specificity, 99 percent. When validated in relation to a
      clinical diagnosis of asthma, the mean sensitivity for the question about self
      reported asthma was 68 percent in the reviewed studies (range, 48 to 100
      percent). The specificity was 94 percent (range, 78 to 100 percent). One problem
      in using the presence of bronchial hyperreactivity (BHR) as a gold standard for
      asthma is that many people with BHR report no respiratory complaints. In other
      words, the presence of BHR is a measure with high sensitivity but low specificity
      for asthma. The effect of using a methacholine challenge test as a standard for
      the disease will thus be an underestimation of the sensitivity of the
      questionnaire.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7802736
TI  - Modes of death in the pediatric intensive care unit: withdrawal and limitation of
      supportive care.
AB  - OBJECTIVE: To determine the frequency of withdrawal or limitation of supportive
      care for children dying in a pediatric intensive care unit (ICU). DESIGN:
      Retrospective review of medical records. SETTING: Pediatric ICU in a tertiary
      care children's hospital. PATIENTS: All children dying in the pediatric ICU over
      a 54-month period (n = 300). INTERVENTIONS: Medical record review. MEASUREMENTS
      AND MAIN RESULTS: Data recorded for each patient included diagnosis, mode of
      death, and whether the child was brain dead. Each patient was assigned to one of
      the following mode of death categories: brain dead; active withdrawal of
      supportive care (meaning removal of the endotracheal tube); failed
      cardiopulmonary resuscitation; allowed to die without cardiopulmonary
      resuscitation (do-not-resuscitate status). A total of 300 patients were
      identified. Diagnoses included postoperative congenital heart disease (n = 56),
      head trauma (n = 38), near-miss sudden infant death syndrome (n = 28), pneumonia
      (n = 22), sepsis (n = 21), near-drowning (n = 21), various anoxic insults (n =
      20), multiple trauma (n = 17), and patients with other diagnoses (n = 77). Mode
      of death was active discontinuation of support in 95 (32%) patients, do-not
      resuscitate status in 78 (26%), brain death in 70 (23%), and failed
      cardiopulmonary resuscitation in 57 (19%). CONCLUSIONS: In a large,
      multidisciplinary pediatric ICU, the most common mode of death was active
      withdrawal of support. In addition, more than half (173/300, 58%) of children
      dying in the pediatric ICU underwent either active withdrawal or limitation (do
      not-resuscitate status) of supportive care.

PMID- 7802737
TI  - Bring back the ward laboratories.

PMID- 7802738
TI  - Use of alfentanil and propofol for difficult tracheal intubation.

PMID- 7802739
TI  - The pendulum and the arterial line.

PMID- 7802740
TI  - NINDS myotatic reflex scale.

PMID- 7802741
TI  - Social work with gay and lesbian adolescents.
AB  - Gay and lesbian adolescents are a socially oppressed group discriminated against
      by a heterosexist and homophobic society. Because of the negative stigma society
      places on lesbian and gay adolescents, they face numerous difficulties that
      require social support and intervention. Issues pertinent to social work with
      lesbian and gay adolescents are examined in the context of three main social
      institutions: the family, the social culture, and the educational setting.
      Suggestions are made for improving intervention with this population, including
      increasing personal awareness of one's own homophobia and heterosexist bias in
      working with client groups; educating oneself and client groups about
      homosexuality; establishing positive social support programs to serve lesbian and
      gay adolescents; advocating for sanctions to end gay and lesbian harassment in
      the educational system; supporting the hiring of openly gay and lesbian teachers
      to serve as positive role models; and advocating for the inclusion of sexual
      orientation information in school sex education curricula.

PMID- 7802742
TI  - Elective ventilation for organ donation.

PMID- 7802743
TI  - Persistence of acute rheumatic fever in the intermountain area of the United
      States.
AB  - We report our 8-year experience with the resurgence of acute rheumatic fever
      during the years 1985 through 1992. The records of 274 confirmed cases referred
      to Primary Children's Medical Center were reviewed. The clinical features
      including the presence of the Jones criteria, demographic data, preceding
      streptococcal infection, and the use of echocardiographic studies were tabulated
      and assessed. Patients came predominantly (84%) from middle-class families with
      access to medical care. Only 46 patients (17%) sought medical attention for a
      preceding sore throat. Carditis evident by auscultation was the dominant major
      manifestation in 68% of the cases. Echocardiography demonstrated mitral
      regurgitation that was not audible in 15 (47%) of 32 patients who had only
      polyarthritis at onset and in 30 (57%) of the 53 who had pure chorea. The
      incidence of acute rheumatic fever has been declining since the peak of the
      outbreak in 1985 but is continuing in the intermountain area at rates comparable
      to those of the 1960s.

PMID- 7802744
TI  - Anal warts and squamous carcinoma-in-situ of the anal canal.

PMID- 7802745
TI  - Audit on myocardial infarction in a district general hospital: is there room for
      improvement in diagnostic accuracy?
AB  - The proportion of patients with an acute myocardial infarction (MI) whose
      diagnosis was missed on admission was accessed. The admitting consultants were
      then tested to see if they could diagnose the patients correctly when they were
      shown the admission histories and electrocardiograms (ECGs). Twenty-six per cent
      of patients with a final diagnosis of MI were not correctly diagnosed on
      admission. Fifty-one per cent of all patients did not receive thrombolytic
      therapy (TT) mainly because the diagnosis was not made on admission. A smaller
      proportion of these patients were admitted to the coronary care unit (CCU). The
      consultants only correctly diagnosed an average of 7.3 of the 20 patients who
      were mis-diagnosed on admission and would have prescribed TT to an average of 4.3
      of these 20 patients. A significant proportion of patients had a diagnosis of MI
      missed on admission and therefore did not receive TT. Therefore, another aid to
      diagnosis such as serum creatinine phosphokinase (CPK) measurement should be
      available as an emergency test.

PMID- 7802746
TI  - History of the condom.

PMID- 7802747
TI  - Reframing pharmacy's leadership, relationship, and scholarship.

PMID- 7802748
TI  - Lack of induction of micronuclei by azidothymidine (AZT) in vivo in mouse bone
      marrow cells.

PMID- 7802749
TI  - Shooting in the dark: estimating the cost of firearm injuries.
AB  - The cost of firearm injuries in the United States in 1990 was an estimated $20.4
      billion. This includes $1.4 billion for direct expenditures for health care and
      related goods, $1.6 billion in lost productivity resulting from injury-related
      illness and disability, and $17.4 billion in lost productivity from premature
      death. While these are the best available national estimates, it is likely that
      they underestimate the economic impact of firearm injuries because they are based
      on relatively old data and on many assumptions necessitated by data gaps. The
      need for better data and improved estimates, and their policy relevance, are
      discussed.

PMID- 7802750
TI  - The distance between the grille of the laryngeal mask airway and the vocal cords.

PMID- 7802751
TI  - An anaesthetic drug error: minimizing the risk.
AB  - A medication error caused a near fatal cardiac arrest in a previously healthy
      patient undergoing elective surgery. Inadvertent epinephrine injection induced
      ventricular dysrhythmias, hypertension, hypotension and pulmonary oedema. The
      case was investigated using critical-incident technique and was reviewed by the
      Risk Management Team of the Department of Anaesthesia. The purpose of this report
      is to present the recommendations resulting from the investigation. These
      include: improved resident training in intravenous drug management, the use of
      anaesthetic drug ampoules with distinct labels, and the development of a
      standardized colour code system for labels on anaesthetic drug ampoules.
      Furthermore, it is recommended that all anaesthetic drug errors be reported to
      the Canadian agencies responsible for drug packaging in order to identify
      patterns in anaesthetic drug errors, and to facilitate the implementation of
      effective drug identification systems.

PMID- 7802752
TI  - Selected strategies for improving sensitivity and reliability of immunoassays.
AB  - Selected recent advances in immunoassay are reviewed. Development has continued
      on new labels (beta-lactamase, pyrophosphatase, luciferases, photoproteins,
      pyridopyridazines, europium cryptates, metal carbonyl complexes, porphines,
      phosphors) and label-detection methods (e.g., chemiluminescence assays,
      thermometric assays, NADP(+)- and FADP-based coupled assays). Various methods
      have been explored to increase assay sensitivity, including label amplification
      via catalyzed reporter deposition (peroxidase label) and immuno-polymerase chain
      reaction (DNA label). The focus of new immunoassay strategies has been on
      improved reliability (bispecific antibodies), assay simplification (piezoelectric
      and surface plasmon resonance immunosensors, phase-modulation fluorescence
      spectroscopy, polymerized bilayer assemblies), and simultaneous multianalyte
      testing (e.g., quadruple labeling with lanthanides, one-step test devices for
      drugs of abuse).

PMID- 7802753
TI  - Family practice residents and future obstetrics practice.

PMID- 7802754
TI  - Acute dystonic reactions complicated by psychotic phenomena.
AB  - Four schizophrenic patients are reported in whom the acute development of
      dystonic muscle spasms, usually involving gaze deviation, was accompanied by the
      exacerbation or appearance of psychotic symptoms. In all cases the relationship
      between the neurological and psychiatric phenomena was close, and sometimes the
      presentation was bizarre or dramatic. The similarity of these states to the
      complex neuropsychiatric disturbances seen in post-encephalitic Parkinsonism is
      emphasised.

PMID- 7802755
TI  - Creatine kinase elevations with clozapine.
AB  - We describe a patient with marked elevations of creatine kinase following
      institution of clozapine treatment. The enzyme levels promptly subsided with
      discontinuation of clozapine. The clinical features did not meet any of the
      published criteria for neuroleptic malignant syndrome.

PMID- 7802756
TI  - Folnegovic & Folnevogic-Smalc's "Schizophrenia in Croatia: inter-regional
      differences in prevalence and a comment on constant incidence".
AB  - "STUDY OBJECTIVE--The aim was to examine why differences exist in schizophrenia
      prevalence and risk in some areas of Croatia, when schizophrenia incidence rates
      do not appear to vary. DESIGN--Areas differing by schizophrenia admission rates
      in patients born in 1953 and admitted by the age of 31 years are compared using a
      number of indicators relating both to general population characteristics and to
      those of schizophrenic cases in these populations. SETTING--The study covers the
      whole of Croatia (4,601,469 inhabitants, 1981 census). SUBJECTS--By the age of 31
      years, out of 80,445 individuals born in Croatia in 1953, 464 were admitted for
      and diagnosed as having schizophrenia. MAIN RESULTS--Admission risk rates are
      higher in those parts of Croatia where emigration rates are high and lower where
      immigration rates are high. There is also a positive correlation with
      schizophrenia prevalence and manic depressive psychosis rates. There is a
      negative correlation with age of onset of schizophrenia and with schizophrenic
      reproduction rates. In the study areas, hospital incidence rates are not
      significantly different. CONCLUSIONS--Economic migration and negative selection
      in the domestic population are likely to be the most significant factors leading
      to differences in schizophrenia prevalence. The approximately equal incidence
      rates in the population, with different prevalence and admission risks, are
      linked to differences in the disease onset among schizophrenics with a positive
      family history for this condition. In other words, these patients, when part of
      the population with a greater prevalence and a greater hereditary loading,
      experience the onset more often at an earlier age. Thus they have a lower
      reproduction rate than in a population with a lower prevalence and a lower
      hereditary loading. Thus incidence rates in populations with different
      prevalences and different hereditary loads are maintained roughly equal over
      generations."

PMID- 7802757
TI  - Acute pericarditis resulting from an endocardial active fixation screw-in atrial
      lead.
AB  - We examined the occurrence of acute pericarditis after pacemaker implantation in
      123 consecutive patients (61 males, 62 females, ages 17-87 years) in whom a newer
      atrial active fixation bipolar lead was inserted endocardially in the right
      atrium for dual chamber pacing. The atrial leads were positioned to obtain the
      best possible pacing and sensing thresholds, after an initial attempt was made
      for insertion into the right atrial appendage or medially into the right atrial
      septum. Six patients (4.9%) developed acute symptomatic pericarditis with
      effusion within 24 hours of implantation. Of these six patients, four had leads
      screwed into the lateral wall, and the other two had leads placed in the
      anterolateral wall. The lead implantation parameters between patients with
      pericarditis and those without did not show any significant difference in the
      atrial P wave amplitude (2.3 +/- 0.4 vs 2.9 +/- 0.9 mV), pacing threshold (1.1 +/
      0.2 vs 1.1 +/- 0.4 V), or resistance (524 +/- 112 vs 480 +/- 94 ohms). All
      symptomatic patients were treated with nonsteroidal anti-inflammatory drugs with
      symptoms resolving in 1-2 weeks. We conclude that: (1) a significant number of
      patients (4.9%) developed acute symptomatic pericarditis after insertion of this
      type of atrial fixation lead; (2) because of the lead design, the implantation
      parameters could not be taken to predict the occurrence of pericarditis; and (3)
      caution should be taken for the insertion of this lead into the thin atrial wall.

PMID- 7802758
TI  - Mild fetal hydronephrosis indicating vesicoureteric reflux.
AB  - The management of neonates with mild hydronephrosis diagnosed antenatally is
      still debated. Although some of these infants are normal, it is recognised that
      others will have mild obstruction of the ureteropelvic junction or vesicoureteric
      reflux (VUR). A prospective study was performed in all newborn infants with an
      antenatal diagnosis of mild hydronephrosis (47 babies, 62 kidneys) born over a
      two year period in order to assess the frequency of VUR. Voiding cystography in
      14 patients with 21 renal units showed VUR. Two patients underwent surgery and
      the VUR resolved; the other 12 received medical treatment. Repeat cystography was
      scheduled for 12-18 months later, when a high rate of spontaneous cure was
      observed. The remaining patients were monitored by ultrasonography but only in
      one case did hydronephrosis deteriorate because of the presence of severe
      ureteropelvic junction obstruction. It is concluded that mild dilatation of the
      pelvis might be an expression of a potentially severe malformation such as VUR,
      and a careful follow up of these cases is mandatory.

PMID- 7802759
TI  - Alternatives to ECMO.
AB  - The past decade has witnessed technological advancements which are unparalleled
      in neonatology. ECMO has been demonstrated to be a powerful rescue treatment, but
      has perhaps been overutilised and is not universally available. Alternative
      treatments have been shown to be both safe and efficacious in the management of
      infants with respiratory failure. Direct head to head clinical trials will
      probably be necessary to establish appropriate criteria and indications for use,
      given the wide diversity of pathophysiology these unique patients present.

PMID- 7802760
TI  - Glue ear.

PMID- 7802761
TI  - The nasopharynx, eustachian tube and otitis media.
AB  - It has been classically hypothesized that a mass in the nasopharynx causes an
      obstacle to air flow through the eustachian tube, thereby creating a negative
      pressure in the middle ear followed by an effusion. However, examination of the
      relevant data concerning the supposed obstruction of the eustachian tube by
      nasopharyngeal carcinomas, choanal polyps and adenoids does not seem to support
      this cause and effect relationship. Evidence points to other more sophisticated
      mechanisms which cause negative pressure and an effusion in pathological middle
      ear conditions. While the hypothesis of a nasopharyngeal mass as the usual
      obstructive cause of middle ear effusion is hard to maintain, evidence does exist
      to support the origin of middle ear infection, as seen in acute and secretory
      otitis media, as being associated, at times, with an ascending infection from the
      nasopharynx.

PMID- 7802762
TI  - Tetrahydrobiopterin synthesis and inducible nitric oxide production in pulmonary
      artery smooth muscle.
AB  - We recently reported (Am. J. Respir. Cell Mol. Biol. 7: 471-476, 1992) that a
      mixture of lipopolysaccharide (LPS) and cytokines produced a time-dependent
      increase in mRNA and protein expression of inducible nitric oxide synthase (iNOS)
      in cultured rat pulmonary artery smooth muscle cells (RPASM). In the current
      study we extend observations on regulation of iNOS in RPASM by showing that de
      novo synthesis of tetrahydrobiopterin (BH4) is critical for LPS and cytokine
      induced NO production. A mixture of LPS and the cytokines gamma-interferon,
      interleukin-1 beta, and tumor necrosis factor-alpha increased steady-state levels
      of mRNA of GTP-cyclohydrolase-I (GTP-CH), the rate-limiting enzyme in BH4
      biosynthesis. Levels of mRNA to GTP-CH became detectable by 4 h, with further
      increases at 24 h by Northern blot analysis and reverse-transcriptase polymerase
      chain reaction. Total intracellular biopterin levels, undetectable under basal
      conditions, increased after 24 h exposure to LPS and cytokines (to 32.3 +/- 0.8
      pmol/mg protein). LPS and cytokine-induced NO production, determined by nitrite
      concentrations in the medium, was decreased in a concentration-dependent manner
      by the GTP-CH inhibitor, 2,4-diamino-6-hydroxypyrimidine (DAHP) at 24 h. DAHP
      also inhibited completely the LPS- and cytokine-induced accumulation of
      intracellular biopterins. Sepiapterin, which supplies BH4 through a salvage
      pathway independent of GTP-CH, reversed the effect of DAHP on LPS and cytokine
      induced NO production.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7802763
TI  - Cerebral palsy and neonatal encephalopathy.
AB  - A retrospective cohort study was carried out to test the hypothesis that children
      born at term with cerebral palsy with signs of neurological dysfunction preceded
      by depression at birth (termed neonatal encephalopathy) differ from those without
      such signs in the frequency of antenatal and perinatal factors, and in the
      severity and characteristics of their impairment and disability. The study was
      carried out in the area covered by Oxford Regional Health Authority. Antenatal,
      intrapartum, neonatal factors, and the later clinical status of the two groups of
      children were used as the main outcome measures. Although most maternal and
      antenatal characteristics were similar in the two groups, the mothers of children
      with a history of neonatal encephalopathy were more likely to be primigravidae
      (odds ratio (OR) 2.0; 95% confidence interval (CI) 1.0 to 4.3) and to have a
      pregnancy of greater than 41 weeks' gestation (OR 3.5; 95% CI 1.0 to 12.1).
      Intrapartum complications were more frequent in the neonatal encephalopathy
      group: meconium staining of the amniotic fluid (OR 3.5; 95% CI 1.5 to 7.8), an
      ominous first stage cardiotocograph (OR 10.2; 95% CI 2.9 to 36.4), with a longer
      median duration of abnormality (200 v 48 minutes). At 5 years of age those with
      neonatal encephalopathy were more likely to have developed spastic quadriplegia
      (OR 4.8; 95% CI 2.2 to 10.5), to have visual impairment (OR 3.0; 95% CI 1.0 to
      8.6), and to be non-walking (OR 4.0; 95% CI 1.8 to 8.8) than those without
      neonatal encephalopathy. Children with cerebral palsy who were born at term and
      have neonatal encephalopathy are more likely to have had signs of intrapartum
      asphyxia and are more likely to have a more severe form of cerebral palsy than
      those without a history of neonatal encephalopathy. Although this group
      represents only one in 10 of all cases of cerebral palsy, some of these may be
      obstetrically preventable.

PMID- 7802764
TI  - Orthopedists have bone to pick with economist over report on chiropractic.

PMID- 7802765
TI  - Alcohol and blood pressure: the INTERSALT study.
AB  - OBJECTIVES: To assess the relation between alcohol intake and blood pressure in
      men and women and in men at younger and older ages; to examine the influence of
      amount and pattern of alcohol consumption, as well as of acute effects, taking
      into account body mass index, smoking, and urinary sodium and potassium
      excretion. DESIGN: Subjects reported alcohol consumption for each of seven days
      before standardised blood pressure measurement, and whether they had consumed any
      alcohol in the 24 hours before measurement. SETTING: 50 centres worldwide.
      SUBJECTS: 4844 men and 4837 women aged 20-59. MAIN OUTCOME MEASURES: Effect of
      alcohol on blood pressure estimated by taking a weighted average of regression
      coefficients from centres. Acute effect assessed by examining mean differences in
      blood pressure of non-drinkers and of heavy drinkers who had and had not consumed
      alcohol in the 24 hours before measurement. Effect of pattern of consumption
      assessed by examining mean differences in blood pressure of non-drinkers compared
      with drinkers (i) whose intake was concentrated in fewer days or who were
      drinking more frequently, and (ii) whose alcohol intake varied little over the
      seven days or varied more substantially, as indicated by the standard deviation
      of daily consumption. RESULTS: Of the 48 centres in which some people reported
      consuming at least 300 ml/week of alcohol, 35 had positive regression
      coefficients linking heavy alcohol consumption to blood pressure. Overall,
      alcohol consumption was associated with blood pressure, significantly at the
      highest intake. After account was taken of key confounders, men who drank 300-499
      ml alcohol/week had systolic/diastolic blood pressure on average 2.7/1.6 mmHg
      higher than non-drinkers, and men who drank > or = 500 ml alcohol/week had
      pressures of 4.6/3.0 mmHg higher. For women, heavy drinkers (> or = 300 ml/week)
      had blood pressures higher by 3.9/3.1 mmHg than non-drinkers. Heavy drinking and
      blood pressure were strongly associated in both sexes, and in men at both younger
      (20-39 years) and older (40-59 years) ages. In men who were heavy drinkers,
      episodic drinkers (those with great variation in daily alcohol consumption) had
      greater differences in blood pressure compared with non-drinkers than did regular
      drinkers of relatively constant amounts. CONCLUSION: The significant relation of
      heavy drinking (3-4 or more drinks/day) to blood pressure, observed in both men
      and women, and in younger and older men, was independent of and added to the
      effect on blood pressure of body mass index and urinary excretion of sodium and
      potassium. The findings indicate the usefulness of targeting those at high risk
      as well as the general population to reduce the adverse effects of alcohol on
      blood pressure.

PMID- 7802766
TI  - The trouble with ethics committees.

PMID- 7802767
TI  - Consequences of varicella and herpes zoster in pregnancy: prospective study of
      1739 cases.
AB  - In a joint prospective study in Germany and the United Kingdom between 1980 and
      1993, 1373 women who had varicella and 366 who had herpes zoster during the first
      36 weeks of gestation were followed up. 9 cases of congenital varicella syndrome
      were identified, all occurring after maternal varicella during the first 20 weeks
      of gestation. The highest risk (2.0%) was observed between 13-20 weeks gestation,
      with 7 affected infants identified among 351 pregnancies (95% CI of risk 0.8
      4.1%). Only 2 cases of congenital varicella syndrome were identified among 472
      pregnancies in which maternal varicella occurred before 13 weeks (observed risk
      0.4%, 95% CI 0.05-1.5%). Herpes zoster in infancy was reported in 10 children
      whose mothers had had varicella in pregnancy. No infants with clinical evidence
      of intrauterine infection were born to the 366 women with herpes zoster in
      pregnancy (upper 95% confidence limit of estimated risk 1.0%). Varicella-zoster
      specific IgM antibody was found at birth in 4 of 16 (25%) infants with clinical
      manifestations of intrauterine infection and persistent specific IgG antibody in
      5 of 7 infants tested. The corresponding rates in asymptomatic infants whose
      mothers had varicella were 12% (76/615) and 7% (22/335) respectively. No
      serological evidence of intrauterine infection was found in infants who mothers
      had herpes zoster in pregnancy. In 97 pregnant women, varicella occurred after
      post-exposure prophylaxis with anti-varicella-zoster immunoglobulin. No cases of
      congenital varicella syndrome or zoster in infancy occurred in this group. Our
      estimates provide a sound basis for counselling women with varicella in
      pregnancy. Although the risk of congenital varicella syndrome is small, the
      outcome for the affected infant is so serious that a reliable method of prenatal
      diagnosis would be valuable. In the long term, prevention of maternal varicella
      would be an option if a safe and effective vaccine were to become routinely
      available.

PMID- 7802768
TI  - Do bedbugs transmit hepatitis B?

PMID- 7802769
TI  - Medical aspects of scuba diving.

PMID- 7802770
TI  - ABC of sports medicine. Sport for people with disability.

PMID- 7802771
TI  - Interpreting precursor studies: what polyp trials tell us about large-bowel
      cancer.

PMID- 7802772
TI  - Caring for adult survivors of child sexual abuse. Issues for family physicians.
AB  - Traditional medical education has not taught physicians about the long-term
      effects of child sexual abuse. Family physicians often feel poorly equipped to
      appreciate the effect of such a childhood history on current health or to
      recognize and treat survivors. This article links the experience of the sexually
      abused child to long-term effects and outlines the role of family physicians in
      screening and caring for survivors.

PMID- 7802773
TI  - The placebo effect: can we use it better?

PMID- 7802774
TI  - Onset of the antidepressant effect of ECT.

PMID- 7802775
TI  - Community survey of long term daytime use of benzodiazepines.

PMID- 7802776
TI  - Antenatal screening for syphilis. Should continue.

PMID- 7802777
TI  - Salivary antibodies to Helicobacter pylori: screening dyspeptic patients before
      endoscopy.
AB  - Diagnostic tests on saliva have advantages compared with those on serum. In 119
      consecutive dyspeptic patients referred for endoscopy we developed and validated
      an enzyme-linked immunosorbent assay to detect salivary immunoglobulins to
      Helicobacter pylori. Salivary IgG distinguished positive and negative cases (p <
      0.0001), but salivary IgA did not. The optimum performance of salivary IgG (85%)
      was similar to that of serum IgG (90%) and better than that of salivary IgA.
      Using our assay and a history of regular use of non-steroidal anti-inflammatories
      in screening patients under 45 years, we detected all peptic ulcers while saving
      39% of endoscopies.

PMID- 7802778
TI  - Recurrent acute interstitial nephritis on rechallenge with omeprazole.

PMID- 7802779
TI  - Successful use of interferon for male infertility.

PMID- 7802780
TI  - Chlorine and organochlorine compounds.

PMID- 7802781
TI  - Upper abdominal pain in pregnancy. Immediate admission is inappropriate.

PMID- 7802782
TI  - Acanthamoeba keratitis.

PMID- 7802783
TI  - Screening for HIV infection. The time has not yet come.

PMID- 7802784
TI  - The sobering D2 story.

PMID- 7802785
TI  - A dermatitis secondary to amino-acid deficiency in treated maple syrup urine
      disease.

PMID- 7802786
TI  - High prevalence of hepatitis E virus antibody in haemodialysis patients.

PMID- 7802787
TI  - The structure of departments of medicine.

PMID- 7802788
TI  - Neospora infection and congenital ataxia in calves.

PMID- 7802789
TI  - Outcomes research in clinical practice. Descriptive studies are unhelpful.

PMID- 7802790
TI  - Lung cancer screening.

PMID- 7802791
TI  - Regarding Yapko's article and the discussion on recovered memories.

PMID- 7802792
TI  - Medical aspects of scuba diving. Standards for diabetic divers are workable.

PMID- 7802793
TI  - Who cares for young carers?

PMID- 7802794
TI  - Screening for breast cancer. Screen women over 65.

PMID- 7802795
TI  - Chinese medical journals. Have much to offer.

PMID- 7802796
TI  - Triglyceride concentration and coronary heart disease. High concentrations need
      treatment.

PMID- 7802797
TI  - Equity in health care.

PMID- 7802798
TI  - Oxygen uptake during rebreathing in a Mapleson A system.

PMID- 7802799
TI  - Delayed cutaneous reaction to unfractionated heparin, low molecular weight
      heparin and danaparoid.

PMID- 7802800
TI  - The influence of occupational activity on the menstrual cycle and fecundability.

PMID- 7802801
TI  - Accepting homosexuality.

PMID- 7802802
TI  - Is it improper billing?

PMID- 7802803
TI  - FRAXAC2 instability.

PMID- 7802804
TI  - Ethics and elective ventilation.

PMID- 7802805
TI  - Cognitive behaviour therapy of schizophrenia. The amenability of delusions and
      hallucinations to reasoning.

PMID- 7802806
TI  - Report on chiropractic.

PMID- 7802807
TI  - Patient satisfaction.

PMID- 7802808
TI  - Specificity problems with Hitachi chloride electrodes.

PMID- 7802809
TI  - Tumor necrosis factor in critical illness.

PMID- 7802810
TI  - A nearly fatal tracheal obstruction resulting from a transtracheal oxygen
      catheter.

PMID- 7802812
TI  - Supraorbital craniotomy.

PMID- 7802811
TI  - Ethical committees and noninformed consent.

PMID- 7802813
TI  - The place of research in the training of NHS consultant physicians.

PMID- 7802814
TI  - Methotrexate may affect certain T lymphocyte subsets in rheumatoid arthritis
      resulting in susceptibility to Pneumocystis carinii infection.

PMID- 7802815
TI  - Management of tetanus: a review of 18 cases.

PMID- 7802816
TI  - Re: Blood levels of organochlorine residues and risk of breast cancer.

PMID- 7802817
TI  - Screening for colorectal cancer: which test is best?

PMID- 7802818
TI  - Health system reform: the case for a single-payer approach.

PMID- 7802819
TI  - Examining product risk in context: the case of zomepirac.

PMID- 7802820
TI  - Does this dizzy patient have a serious form of vertigo? Comment and correction.

PMID- 7802821
TI  - Varicella in pregnancy.

PMID- 7802822
TI  - Do bedbugs transmit hepatitis B?

PMID- 7802823
TI  - Salivary antibodies to Helicobacter pylori: screening dyspeptic patients before
      endoscopy.

PMID- 7802824
TI  - Cholera treatment.

PMID- 7802825
TI  - What causes Chinese paralytic syndrome?

PMID- 7802826
TI  - Game, set and MRCP.

PMID- 7802827
TI  - Quinacrine sterilisation.

PMID- 7802828
TI  - Hepatitis E virus antibody prevalence.

PMID- 7802829
TI  - High-titre measles vaccines for boys.

PMID- 7802830
TI  - Antiphospholipid antibodies in children with idiopathic cerebral ischaemia.

PMID- 7802831
TI  - Associations between plasma insulin and lipoprotein concentrations in first
      degree relatives of insulin-dependent diabetes mellitus probands.

PMID- 7802832
TI  - Japanese B encephalitis vaccine. Time for a reappraisal?

PMID- 7802833
TI  - Reconsidering HIV screening in physicians.

PMID- 7802834
TI  - HIV prevention programs.

PMID- 7802835
TI  - DNA fingerprinting.

PMID- 7802836
TI  - Sources of dioxin.

PMID- 7802837
TI  - Publish more articles.

PMID- 7802838
TI  - Classification of P2 purinoceptors. Not all G protein-coupled P2 purinoceptors
      can be classed as P2Y.

PMID- 7802839
TI  - Tyrosine phosphorylation and Ca2+ influx. A further mechanism for store-dependent
      Ca2+ entry?

PMID- 7802840
TI  - Laser dosimetry in the prostate.

PMID- 7802841
TI  - Embryonic mortality in cattle.

PMID- 7802842
TI  - Primary care at a crossroads.

PMID- 7802843
TI  - Prothrombin time using thromboplastins of different origin in hemophilia BM
      patients.

PMID- 7802844
TI  - Two-locus versus one-locus lods for complex traits.

PMID- 7802845
TI  - The axillary vein as an alternative.

PMID- 7802846
TI  - Another explanation for reduced meperidine consumption in the immediate
      postoperative period.

PMID- 7802847
TI  - Combined epidural/general anesthetic technique and severe coronary artery
      stenosis.

PMID- 7802848
TI  - Developmental setback in severe visual impairment.

PMID- 7802849
TI  - HIV infection and the dentist.

PMID- 7802850
TI  - Social competence and adolescent psychosis.

PMID- 7802851
TI  - Safety and side-effects of alprazolam. Controlled study in agoraphobia with panic
      disorder.
AB  - BACKGROUND: The widespread use of benzodiazepines has led to increasing
      recognition of their unwanted effects. The efficacy of alprazolam and placebo in
      panic disorder with agoraphobia, and the side-effect and adverse effect profiles
      of both drug groups were measured. METHOD: In London and Toronto 154 patients who
      met DSM-III criteria for panic disorder with agoraphobia were randomised to
      alprazolam or placebo. Subjects in each drug group also received either exposure
      or relaxation. Treatment was from weeks 0 to 8 and was then tapered from weeks 8
      to 16. RESULTS: Mean alprazolam dose was 5 mg daily. Compared with placebo
      subjects, alprazolam patients developed more adverse reactions (21% v. 0%) of
      depression, enuresis, disinhibition and aggression; and more side-effects,
      particularly sedation, irritability, impaired memory, weight loss and ataxia.
      Side-effects tended to diminish during treatment but remained significant at week
      8. Despite this, the drop-out rate was low. CONCLUSIONS: Alprazolam caused side
      effects and adverse effects during treatment but many patients were willing to
      accept these.

PMID- 7802852
TI  - Comparison of the efficacy, safety and withdrawal of alpidem and alprazolam in
      anxious patients.
AB  - BACKGROUND: We investigated whether a new non-benzodiazepine anti-anxiety drug,
      alpidem, produces weaker withdrawal symptoms than alprazolam. METHOD: Under a
      double-blind procedure, 122 patients suffering from general anxiety disorders
      were randomly allocated to either alpidem (50 mg, three times a day) or
      alprazolam (0.5 mg, three times a day) for six weeks, followed by a two-week
      placebo withdrawal phase. The diagnosis of withdrawal syndrome (WS) was made, in
      blind conditions, on the basis of the Withdrawal Symptom Check List (WSCL), after
      one or two weeks of discontinuation of active treatment. RESULTS: The WS occurred
      significantly less frequently in the alpidem group (n = 10, 18%) than in the
      alprazolam group (n = 26, 48%). Typical withdrawal symptoms on the WSCL were also
      significantly less severe (P = 0.044) in the alpidem group compared with the
      alprazolam group. CONCLUSIONS: Alpidem may be a valid alternative to current
      benzodiazepine anxiolytic therapy because it produces fewer and weaker withdrawal
      symptoms than alprazolam and is better tolerated.

PMID- 7802853
TI  - Interpersonal conflict and physical violence during the childbearing year.
AB  - Reducing physical abuse directed at women by male partners is one of the nation's
      Year 2000 health objectives. An important target group for achieving this health
      objective is pregnant women. The present study examines the frequency, severity,
      perpetrators and psychosocial correlates of violence during the childbearing
      year. A panel of 275 women were interviewed 3 times during pregnancy and at 6
      months postpartum. Moderate or severe violence was somewhat more common during
      the postpartum period than during the prenatal period--19% of women reported
      experiencing moderate or severe violence prenatally, compared to 25% in the
      postpartum period. For partner-perpetrated violence, being better educated was
      associated with increased risk of violence as was having had a sex partner who
      ever shot drugs; being older, having a confidant and having social support from
      friends were significant protective factors. For violence perpetrated by someone
      other than a male partner, having a confidant was a significant protective
      factor. Obstetric care providers who routinely come in contact with pregnant
      women, as well as emergency department staff, need to be systematically screening
      for violence against women. Efforts to enhance women's social support networks
      should be included in primary and secondary prevention programs.

PMID- 7802854
TI  - Mortality and cancer morbidity of Finnish chlorophenoxy herbicide applicators: an
      18-year prospective follow-up.
AB  - An 18-year follow-up for mortality and cancer morbidity was conducted in a cohort
      of 1,909 men who had started spraying chlorophenoxy herbicides (mixture of 2,4
      dichlorophenoxyacetic acid [2,4-D] and 2,4,5-trichlorophenoxyacetic acid [2,4,5
      T]) in 1955 through 1971. In all, 384 persons had died during the follow-up, and
      there was a slight deficit in natural deaths (standardized mortality ratio [SMR]
      0.84; 95% confidence interval [CI] 0.75-0.94). By contrast, there was a small,
      nonsignificant increase in accidental and violent deaths. The overall cancer
      mortality was slightly less than in the general population (SMR 0.83; 95% CI 0.65
      1.02), and not a single case of death of non-Hodgkin's lymphomas (NHL) or soft
      tissue sarcomas (STS) was detected. With regard to cancer morbidity, the incident
      cases showed a slight deficit compared to the population figure (standardized
      incidence ratio [SIR] 0.81; 95% CI 0.67-0.97). One case of NHL was found (2.4
      expected with 10 years of latency), but not a single case of STS (0.8 expected
      with 10 years of latency). While our study does not support the contention that
      spraying of 2,4-D and 2,4,5-T containing herbicides carries any significant risk
      of cancer, the medium to low statistical power of the study does not allow any
      far reaching negative conclusions regarding the carcinogenicity of the agents.

PMID- 7802855
TI  - Effect of the selection pressure with anti-VP7 and anti-VP4 neutralizing
      monoclonal antibodies on reassortant formation between two human rotaviruses.
AB  - In order to study the effect of selection pressure of anti-VP4 and anti-VP7
      neutralizing monoclonal antibodies(N-MAbs) on reassortant formation, 424
      reassortant clones were produced from mixed cultures of human rotavirus strains
      Wa and HN126 and their genotypes were analysed. Reassortant selection was done
      with four types of N-MAb: anti-VP4 MAb to Wa and anti-VP7 MAb to HN126(selection
      A); anti-VP4 MAb to HN126 and anti-VP7 MAb to Wa(selection B); anti-VP7 MAb to
      Wa(selection C); and anti-VP4 MAb to Wa(selection D). In each selection
      experiment, more than 100 clones were isolated, and the parental origin of RNA
      segments was identified by polyacrylamide gel electrophoresis. All clones
      isolated by selections A and B were found to be antigenic mosaic reassortants
      with the VP4 gene of HN126 and the VP7 gene of Wa and antigenic mosaic
      reassortants with the VP4 gene of Wa and the VP7 gene of HN126, respectively.
      Although in reassortants of both selections, RNA segments 2, 3, 5 and 6 were
      selected from strain Wa at considerably high rates, selection rates of RNA
      segments 1, 7, 8, and 11 were significantly different between selection A and B.
      In reassortants from selection C and D, selection rates of RNA segments 1, 3, 6,
      7, 8, and 11 from Wa were significantly lower than those in selection A and B,
      whereas RNA segments 2 and 5 were almost exclusively selected from Wa as observed
      in selection A and B. These results indicated the presence of two types of
      nonrandom gene selection in reassortant formation, one strongly dependent on, and
      another irrespective of, the selection pressure with N-MAbs.

PMID- 7802856
TI  - The evolution of acute stroke recorded by multimodal magnetic resonance imaging.
AB  - Events associated with an evolving cerebral infarction were studied using
      multiple magnetic resonance imaging (MRI) techniques at 4.7 T in a rat model of
      middle cerebral artery occlusion. High resolution perfusion images revealed a
      core of absent perfusion surrounded by a zone of slow, but measurable perfusion.
      Only the core of severest perfusion deficit demonstrated restricted water
      diffusion as early as 1 hr, consistent with "cytotoxic" cellular edema in the
      most vulnerable region. Within 24 hours, the area of restricted diffusion
      encompassed the entire region destined to become infarcted. In spin-echo images,
      hypointensity, likely reflecting deoxygenated hemoglobin, was visible in the
      ischemic hemisphere. Edema accumulated over 72 hr primarily in the surrounding
      slowly perfused rim, consistent with the concept of "vasogenic" edema. These
      studies demonstrate that multimodal MRI can visualize events which define the
      ischemic penumbra--deoxygenation, maintenance of transmembrane ionic gradients,
      reduced flow, and delayed cell death. These experiments noninvasively visualized
      differential hemodynamic and biochemical processes within the core and perifocal
      penumbra and will allow quantitation over time of the relationship between blood
      flow, cytotoxicity and edema in stroke.

PMID- 7802857
TI  - Variability of DA/DAPI and C heterochromatic regions: a population study.
AB  - DA/DAPI and C chromosomal heteromorphic sites (1q, 9q, 15p, 16q, Yq) in a sample
      of 136 unrelated individuals from the Garfagnana valley (Tuscany, Italy) have
      been analyzed quantitatively and qualitatively. The variations in length, between
      homolog heteromorphisms, and intensity of fluorescence of the heterochromatic
      bands have been compared in two subsamples of the population (upper and middle
      valley) individualized according to geodemographic criteria. DA/DAPI
      heterochromatin differed significantly from C heterochromatin, showing a lower
      average amount and a higher variability at each site. This suggests a
      differential staining of DNA of the two banding systems. Furthermore, DA/DAPI
      heterochromatin was less uniformly distributed in the population than C
      heterochromatin and the regions 16q and Yq discriminated better between
      subsamples. The variations of DA/DAPI fluorescence at the 15p site demonstrated
      an excess of homomorphic individuals in the upper valley, which could be related
      to the mating structure of the population living in this area.

PMID- 7802858
TI  - Long-range photoinduced electron transfer through a DNA helix.
AB  - Rapid photoinduced electron transfer is demonstrated over a distance of greater
      than 40 angstroms between metallointercalators that are tethered to the 5'
      termini of a 15-base pair DNA duplex. An oligomeric assembly was synthesized in
      which the donor is Ru(phen)2dppz2+ (phen, phenanthroline, and dppz,
      dipyridophenazine) and the acceptor is Rh(phi)2phen3+ (phi, phenanthrenequinone
      diimine). These metal complexes are intercalated either one or two base steps in
      from the helix termini. Although the ruthenium-modified oligonucleotide
      hybridized to an unmodified complement luminesces intensely, the ruthenium
      modified oligomer hybridized to the rhodium-modified oligomer shows no detectable
      luminescence. Time-resolved studies point to a lower limit of 10(9) per second
      for the quenching rate. No quenching was observed upon metallation of two
      complementary octamers by Ru(phen)3(2+) and Rh(phen)3(3+) under conditions where
      the phen complexes do not intercalate. The stacked aromatic heterocycles of the
      DNA duplex therefore serve as an efficient medium for coupling electron donors
      and acceptors over very long distances.

PMID- 7802859
TI  - A new antibiotic, cypemycin. Taxonomy, fermentation, isolation and biological
      characteristics.
AB  - A new peptide antibiotic, cypemycin, with a molecular weight of 2,097 (M+H), was
      isolated from the culture broth of Streptomyces sp. OH-4156. The antibiotic
      possesses cytocidal activity against P388 leukemia cells in vitro at a
      concentration of 1.3 microgram/ml (IC50 values), and the antibiotic showed
      antimicrobial activities against Micrococcus luteus (MIC, 0.2 microgram/ml).

PMID- 7802860
TI  - Inhibition of UDP-GlcNAc:Gal beta 1-3GalNAc-R (GlcNAc to GalNAc) beta 6-N
      acetylglucosaminyltransferase from acute myeloid leukaemia cells by photoreactive
      nitrophenyl substrate derivatives.
AB  - Cells from patients with acute myeloid leukaemia (AML) contain an abnormally high
      UDP-GlcNAc: Gal beta 1-3GalNAc-R (GlcNAc to GalNAc) beta 6-N
      acetylglucosaminyltransferase (core 2 beta 6-Gn-T) activity. Upon UV irradiation
      at 350 nm, the substrate Gal beta 1-3GalNAc alpha-p-nitrophenyl acted as an
      effective inhibitor for this enzyme but not for several other transferases.
      Preincubation with Gal beta 1-3GalNAc alpha-benzyl but not GalNAc alpha-benzyl
      protected core 2 beta 6-Gn-T from inhibition indicating that the inhibitor is
      specific for the substrate binding site of core 2 beta 6-Gn-T. A number of other
      nitrophenyl-sugar derivatives similarly acted as inhibitors for core 2 beta 6-Gn
      T. GalNAc alpha-pnp at higher concentrations also inactivated UDP-Gal: GalNAc-R
      beta 3-galactosyltransferase from rat liver and AML cells and inhibition could be
      reduced by substrate protection. These results suggest that pnp-sugar derivatives
      may prove useful as specific inhibitors of glycosyltransferases and as affinity
      labels.

PMID- 7802861
TI  - In vitro activity of DMG-Mino and DMG-DM Dot, two new glycylcyclines, against
      anaerobic bacteria.
AB  - The in vitro activity of DMG-Mino and DMG-DM Dot against 350 anaerobic bacterial
      strains including anaerobic cocci, Propionibacterium acnes, Clostridium
      perfringens, Clostridium difficile, Bacteroides fragilis, other Bacteroides
      species and fusobacteria was determined by the agar dilution method. Their
      activity was compared with that of minocycline, doxycycline, piperacillin,
      cefoxitin, imipenem, clindamycin and metronidazole. DMG-Mino and DMG-DM Dot and
      imipenem were the most active agents tested. DMG-Mino and DMG-DM Dot had in vitro
      activity superior to that of minocycline and doxycycline.

PMID- 7802862
TI  - Pharmacokinetics of Clivarin a new low molecular weight heparin in healthy
      volunteers.
AB  - The antithrombotic activity and pharmacokinetics of Clivarin, a low molecular
      weight heparin was randomly studied in 10 healthy male volunteers. Doses of 20,
      40, 60 and 80 anti F Xa U/kg BW were injected intravenously and subcutaneously in
      crossover fashion. The heparin concentrations were measured by inhibition of
      clotting assays (anti IIa and anti Xa activities using amidolytic assays and
      [dilute] thrombin time). The pharmacokinetic profile of Clivarin is characterized
      by a linear relationship between dose and absorption, relatively low clearance
      and a long elimination half-life, and a high anti Xa/anti IIa ratio of 5.3.

PMID- 7802863
TI  - MLR-52, (4'-demethylamino-4',5'-dihydroxystaurosporine), a new inhibitor of
      protein kinase C with immunosuppressive activity.
AB  - In the course of screening with the mixed lymphocyte reaction, a new inhibitor of
      protein kinase C with immunosuppressive activity was isolated from the
      fermentation broth and mycelia of Streptomyces sp. AB 1869R-359. Although certain
      similarities exist, this strain is morphologically and physiologically distinct
      from other reported producers of staurosporine-related compounds. We have found
      that this strain produces relatively high levels of staurosporine and the new
      minor compound MLR-52, which possesses the indolo[2,3-a]carbazole chromophore of
      staurosporine, but differs in the substitution pattern of the sugar moiety. Their
      structures have been elucidated by mass and NMR spectra. MLR-52 has been shown to
      inhibit the enzymatic activity of protein kinase C and the murine mixed
      lymphocyte reaction.

PMID- 7802864
TI  - Cardiac electrophysiologic and antiarrhythmic actions of two long-acting
      spirobenzopyran piperidine class III agents, L-702,958 and L-706,000 [MK-499].
AB  - The cardiac electrophysiologic and antiarrhythmic actions of two Class III ketone
      and alcohol-containing spirobenzopyran piperidine analogs, L-702,958 and L
      706,000 [MK-499], respectively, were assessed in vitro and in vivo. L-702,958 and
      L-706,000 [MK-499] selectively blocked the rapidly activating component of the
      delayed rectifier K+ current in guinea pig isolated ventricular myocytes (IC50
      values, 14.6 and 43.9 nM, respectively), and prolonged effective refractory
      period in ferret isolated papillary muscles (EC25 values, 10.5 and 53.8 nM,
      respectively). In anesthetized dogs, L-702,958 and L-706,000 [MK-499] increased
      ventricular refractory periods (ED20 values, 3.3 and 9.2 micrograms/kg i.v.,
      respectively) and concomitantly increased ECG QT interval and left
      ventricular+dP/dt. Cumulative i.v. administrations of up to 100 micrograms/kg of
      L-702,958 and 300 micrograms/kg L-706,000 [MK-499] in anesthetized dogs increased
      atrial and ventricular refractoriness and prolonged the ECG QT interval, but did
      not alter atrial, atrioventricular nodal, His-Purkinje or ventricular conduction
      indices. In anesthetized dogs studied chronically (9.2 +/- 1.1 days) after
      anterior myocardial infarction, the cumulative i.v. administrations of 100
      micrograms/kg of L-702,958 and 300 of micrograms/kg L-706,000 [MK-499] suppressed
      the induction of ventricular tachyarrhythmia by programmed ventricular
      stimulation (suppression rates: 8 of 10, 80% and 9 of 11, 82%, respectively) and
      reduced the incidence of lethal ventricular arrhythmias (incidence of lethal
      ischemic arrhythmias: 4 of 10, 40% and 1 of 11 9%, respectively, compared to 34
      of 40, 85%, in vehicle controls. L-702,958 and L-706,000 [MK-499] (cumulative 100
      and 300 micrograms/kg i.v., respectively) did not facilitate the induction of
      arrhythmias by programmed ventricular stimulation in postinfarction dogs. After
      equivalently effective p.o. doses in conscious dogs, L-702,958 (10 micrograms/kg)
      and L-706,000 [MK-499] (30 micrograms/kg) increased ECG QT interval with long
      durations of action of approximately 9 and 14 hr, respectively. L-706,000 [MK
      499] elicited a more consistent and sustained prolongation of the QT interval
      than L-702,958. These findings show that both L-702,958 and L-706,000 [MK-499]
      are potentially useful agents for the prevention of malignant ventricular
      arrhythmias in the setting of myocardial ischemic injury.

PMID- 7802865
TI  - Sensitive enantiomeric separation of aliphatic and aromatic amines using aromatic
      anhydrides as nonchiral derivatizing agents.
AB  - New pre-column derivatizing reagents: phthalic anhydride, 3-nitrophthalic
      anhydride, diphenic anhydride, 1,8-naphthalic anhydride and diphenylmaleic
      anhydride have been developed for resolving chiral compounds having amine groups.
      Although all of these agents produce derivatives with high molar absorptivities,
      the later two also fluoresce. Upon derivatization, aromatic analytes containing
      free carboxylic groups are produced. Both of these moieties enhance chiral
      recognition on cyclodextrin-based columns. The derivatization reaction is carried
      out at room temperature by shaking a buffered aqueous solution of a sample with
      an acetonitrile solution of the reagent. The reaction is fast and proceeds
      without any detectable racemization. The labeled compounds have favorable
      chromatographic properties which are demonstrated by resolution of a number of
      chiral compounds on cyclodextrin-bonded phases operated with non-aqueous polar
      organic eluents. The selectivity and good efficiency of this system contributes
      to its high sensitivity and in its applicability for detecting low levels of
      enantiomeric impurities. The detection limit is in the picomole range and less
      than 0.1% enantiomeric impurities can be determined in some cases.

PMID- 7802866
TI  - Magnetoferritin: characterization of a novel superparamagnetic MR contrast agent.
AB  - A protein-encaged superparamagnetic iron oxide has been developed and
      characterized by using horse spleen apoferritin as a novel bioreactive
      environment. The roughly spherical magnetoferritin molecules, 120 A in diameter,
      are composed of a monocrystalline maghemite or magnetite core 73 A +/- 14 in
      diameter. Except for the additional presence of iron-rich molecules of higher
      molecular weight, the appearance and molecular weight (450 kd) of magnetoferritin
      are identical to that of natural ferritin; the molecules are externally
      indistinguishable from their precursor, with a pI (isoelectric point) in the
      range 4.3-4.6. The measured magnetic moment of the superparamagnetic cores is
      13,200 Bohr magnetons per molecule, with T1 and T2 relaxivities (r1 and r2) of 8
      and 175 L.mmol-1 (Fe).sec-1, respectively, at body temperature and clinical field
      strengths. The unusually high r2/r1 ratio of 22 is thought to arise from ideal
      core composition, with no evidence of crystalline paramagnetic inclusions. T2
      relaxation enhancement can be well correlated to the field-dependent molecular
      magnetization, as given by the Langevin magnetization function, raised to a power
      in the range 1.4-1.6. With its nanodimensional biomimetic protein cage as a
      rigid, convenient matrix for complexing a plethora of bioactive substances,
      magnetoferritin may provide a novel template for specific targeting of selected
      cellular sites.

PMID- 7802867
TI  - Protein synthesis in the developing rat liver: participation of initiation
      factors eIF-2 and eIF-2B.
AB  - We studied the decline in protein synthesis in the developing liver in suckling
      rats (4 to 10 days) and adult rats (2 mo). The rate of protein synthesis was
      measured with a cell-free system and compared with the activity of two initiation
      factors, eukaryotic initiation factor-2 and eukaryotic initiation factor-2B, and
      with casein kinase II, which phosphorylates both factors in vitro. The specific
      activity of the three parameters decreased in adult rats compared with suckling
      rats and in parallel to the rate of protein synthesis. Quantification of
      eukaryotic initiation factor-2 in the ribosomal salt wash and in the
      postmicrosomal supernatant showed that both the specific activity and the levels
      of eukaryotic initiation factor-2, are much higher in the ribosomal salt wash
      fractions than in postmicrosomal supernatants, but no differences were found
      between the two age groups. The eukaryotic initiation factor-2/ribosome ratio was
      higher in adult rats than in suckling rats, and this parameter seems to be
      inversely proportional to the rate of protein synthesis. The phosphorylation
      state of eukaryotic initiation factor-2 alpha, as determined by isoelectric
      focusing followed by protein immunoblotting, revealed very low and equal levels
      of phosphorylation in the two animal groups. The lack of changes in eukaryotic
      initiation factor-2 levels and phosphorylation status suggests that a decrease in
      the activity or levels of eukaryotic initiation factor-2B could be responsible
      for the decrease in eukaryotic initiation factor-2 activity and account for, at
      least in part, the differences observed in the rates of protein synthesis.

PMID- 7802868
TI  - A unique pattern of lymphokine synthesis is a characteristic of certain antigen
      specific suppressor T cell clones.
AB  - We report that the lymphokines (IFN-gamma) and IL-10 are co-synthesized by
      previously described CD3+ TCR alpha beta+, minor antigen-specific suppressor T
      cell clones. IFN-gamma and IL-10 are known to (i) be characteristically produced
      by different helper T cell types, Th1 and Th2 respectively, and (ii) inhibit the
      function of the reciprocal subset of T cells: IFN-gamma inhibits the function of
      Th2 and IL-10 that of Th1 cells. Although Th0 cells are also known to synthesize
      cytokines of both the Th1- and Th2-type T cells, the suppressor T cells described
      in this report are different from Th0 cells in that they produce (i) neither IL-2
      nor IL-4 molecules and (ii) stimulation via their CD3-TCR system seems
      independent of both IL-2 and IL-4, the typical autocrine molecules for T cell
      proliferation. The lymphokine profile of these suppressor T (Ts) cell clones, as
      well as those of human antigen-specific Ts cells reported earlier, suggests that
      co-synthesis of some Th1-like and some Th2-like cytokines may be a characteristic
      of antigen-specific Ts cells as opposed to the type of reciprocal inhibition
      mediated through IFN-gamma or IL-10, which is antigen non-specific.

PMID- 7802869
TI  - Structural determinants of peptide-binding orientation and of sequence
      specificity in SH3 domains.
AB  - The Src-homology-3 (SH3) domains of the Caenorhabditis elegans protein SEM-5 and
      its human and Drosophila homologues, Grb2 and Drk (refs 1-4), bind proline-rich
      sequences found in the nucleotide-exchange factor Sos as part of their proposed
      function linking receptor tyrosine kinase activation to Ras activation. Here we
      report the crystal structure at 2.0 A resolution of the carboxy-terminal SH3
      domain from SEM-5 complexed to the mSos-derived amino-acid sequence PPPVPPRRR.
      The peptide is found to bind in an orientation ('minus') that is precisely
      opposite to that observed previously ('plus' orientation) in other SH3-peptide
      complexes. This novel ability of peptide-recognition proteins to recognize
      peptides in two distinct modes may play an important role in the signalling
      specificity of pathways involving SH3 domains. Comparison of this structure with
      other SH3 complexes reveals how a conserved binding face can be used to recognize
      peptides in different orientations, and why the Sos peptide binds in this
      particular orientation.

PMID- 7802870
TI  - Metacarpophalangeal joint prostheses: a review of past and current designs.
AB  - The anatomy and biomechanics of the metacarpophalangeal (MCP) joint are briefly
      described. Hinge, flexible and surface designs of past and current MCP prosthetic
      joints are reviewed, outlining their respective advantages and disadvantages.
      Although existing prostheses can restore cosmetic appearance and relieve pain,
      none can equal the stability and versatility of the natural joint. Delayed
      reconstructive surgery may be partly responsible for the mediocre results
      experienced, since the later the surgery the worse will be the condition of the
      muscles and ligaments surrounding the joint. These are the structures responsible
      for strength, movement and stability of the joint. From a mechanical viewpoint it
      may be desirable to operate at an earlier stage of the disease than is currently
      indicated, but this is a clinical decision. Some design aspects, namely fixation
      and wear, require a different approach when designing an MCP prosthesis from that
      adopted in the case of prosthetic hips and knees.

PMID- 7802871
TI  - An instrumented glove for monitoring MCP joint motion.
AB  - A lycra glove has been instrumented with novel low-profile electrogoniometers to
      measure index and middle finger metacarpophalangeal (MCP) flexion/extension
      motion. It is lightweight and comfortable to wear, enabling portable, unobtrusive
      measurement of joint usage about the home or work environment. Preliminary
      results have shown it to be of comparable accuracy to existing clinical
      measurements. Many applications are envisaged in the fields of ergonomics,
      orthopaedics and rehabilitation.

PMID- 7802873
TI  - Interaction between the joints in the shoulder mechanism: the function of the
      costoclavicular, conoid and trapezoid ligaments.
AB  - By developing a measurement method based on the palpation of bony landmarks, the
      three-dimensional positions of the scapula and clavicle can be measured at
      several angles of humerus elevation. An analysis of these measurements shows the
      interaction between all joints of the shoulder mechanism. With the help of a
      biomechanical shoulder model the role of some of the extracapsular ligaments in
      the motion pattern of scapula and clavicle can be derived. In addition, the
      interaction between the rotations in the acromioclavicular and sternoclavicular
      joints is shown, and the possible implications for the treatment of joint
      problems in the shoulder are discussed.

PMID- 7802872
TI  - A kinematic technique for describing wrist joint motion: analysis of
      configuration space plots.
AB  - This paper describes an experimental method for determining the minimum number of
      degrees of freedom of a human joint. Application of this technique to the wrist
      suggests that the normal, intact wrist joint uses only two degrees of freedom to
      move in a plane that is not aligned with the anatomic planes. The technique may
      be useful in identifying emerging joint pathologies and in simplifying kinematic
      models of joint function.

PMID- 7802874
TI  - Strain gauged six-component load transducer for use in upper limb biomechanics.
AB  - A six-channel instrumented load transducer has been developed for measuring hand
      and upper limb loading (maximum design load, 2 kN). Modular in design, the
      transducer can be adapted to a variety of formats, thereby increasing the range
      of activities to which it can be applied. When used with a motion analysis
      system, hand loading can be determined with respect to a laboratory coordinate
      system irrespective of transducer orientation and position. Measurement accuracy
      of approximately +/- 1 per cent of applied loading has been determined through a
      system calibration.

PMID- 7802876
TI  - Asperity lubrication in human joints.
AB  - The asperity lubrication in human joints is examined in the present paper, with
      particular reference to the tertiary undulation with wavelengths of around 20-45
      microns. It was found that, under dynamic physiological loading conditions, the
      secondary waviness of the cartilaginous surface (typically 0.5 mm wavelength)
      could be effectively flattened to sustain a fluid film of 0.1-0.3 micron thick,
      while the tertiary waviness could be squashed to sustain a much thinner fluid
      film of 0.01 micron (10 nm) thick with normal synovial fluid as the lubricant.
      The calculated film thickness for the tertiary undulation was less than 5 nm when
      the ankle joint was lubricated by Ringer's solution or pathological synovial
      fluids, or when only quasi-static loading conditions were considered, while a
      sufficiently thick fluid film could still be formed when the secondary
      undulations were considered alone. It was thus suggested that the fluid film
      lubrication mechanism was operative for human joints with normal synovial fluid
      as the lubricant under physiological dynamic loading conditions and the mixed
      lubrication mechanism could take over when static loading conditions prevailed or
      when watery lubricants (eta approximately 0.001 Pa s) were used.

PMID- 7802875
TI  - Utilization of upper limb joint replacements during 1972-90: the Mayo Clinic
      experience.
AB  - Increasing application of expensive medical technologies, including joint
      replacement, is of concern in the current economic climate. Successful upper limb
      joint replacements (ULJRs) are being performed, but few detailed data about their
      utilization are available. To explore the resource implications of such surgery,
      the utilization of total shoulder replacement (TSR), total elbow replacement
      (TER) and total wrist replacement (TWR) were examined from the time these
      procedures first became available at the Mayo Clinic up to 1990. The age- and sex
      adjusted utilization rate for TSR among Olmsted County, Minnesota, residents was
      1.8 per 100,000 person-years (p-y), 0.8 per 100,000 p-y for TER and 1.1 per
      100,000 p-y for TWR. Overall utilization of primary ULJR among Olmsted County
      residents during the 19-year study period was 3.8 per 100,000 p-y. The commonest
      indication for TSR was osteoarthritis (46 per cent) and for TER and TWR was
      rheumatoid arthritis (50 and 81 per cent respectively). There was no consistent
      trend in the utilization of these procedures among Olmsted County residents, but
      the number of referral patients receiving a ULJR at the Mayo Clinic increased
      steadily during the study period. The Mayo Clinic experience suggests an
      increasing demand for ULJR, particularly TSR and TER. With continued advances in,
      and diffusion of, the technology this demand may increase further.

PMID- 7802877
TI  - Finite element analysis of poor distal contact of the femoral component of a
      cementless hip endoprosthesis.
AB  - The difficulty of achieving good distal contact between a cementless hip
      endoprosthesis and the femur is well established. This finite element study
      investigates the effect on the stress distribution within the femur due to
      varying lengths of distal gap. Three-dimensional anatomical models of two
      different sized femurs were generated, based upon computer tomograph scans of two
      cadaveric specimens. A further six models were derived from each original model,
      with distal gaps varying from 10 to 60 mm in length. The resulting stress
      distributions within these were compared to the uniform contact models. The
      extent to which femoral geometry was an influencing factor on the stress
      distribution within the bone was also studied. Lack of distal contact with the
      prosthesis was found not to affect the proximal stress distribution within the
      femur, for distal gap lengths of up to 60 mm. In the region of no distal contact,
      the stress within the femur was at normal physiological levels associated with
      the applied loading and boundary conditions. The femoral geometry was found to
      have little influence on the stress distribution within the cortical bone.
      Although localized variations were noted, both femurs exhibited the same general
      stress distribution pattern.

PMID- 7802878
TI  - Failure of joint prostheses.

PMID- 7802879
TI  - [Results of accelerated radiotherapy and simultaneous carboplatin administration
      in inoperable head-neck cancers].
AB  - Until now, radical irradiation has been the treatment of choice for patients with
      unresectable squamous cell carcinomas of the head and neck. In spite of improved
      radiation techniques, conventional radiotherapy remains mainly palliative for
      patients with advanced and unresectable disease stages. Our own results with
      accelerated radiotherapy (2 x 2.1 Gy/day, day 1-4 in week 1, 2, 5 and 6, total
      dose of 67.2 Gy) and simultaneous chemotherapy with carboplatin (50
      mg/m2/treatment day) suggest that combined radiochemotherapy might improve the
      poor results achieved with conventional radiotherapy or sequential
      chemoradiotherapy in these patients. However, further studies are necessary to
      clarify whether modified radiotherapy or simultaneous chemotherapy or the
      combination of both are the reason for the improved treatment results.
      Furthermore, accelerated radiotherapy and simultaneous chemotherapy should also
      be investigated as an adjuvant postoperative treatment modality in primary
      resectable patients with advanced stage of disease to improve their poor
      prognosis.

PMID- 7802880
TI  - [A computer simulation of outcome in early screening studies of cancers of the
      mouth cavity].
AB  - The purpose of the simulation was to design a specific cancer screening programme
      for squamous cell carcinomas of the head and neck to make detailed estimates of
      the outcomes of different screening programme options. Therefore, a mathematical
      model of screening (Eddy) was transformed and simulated with a computer
      programme. The model is designed as a Markov chain with 7 states and filled with
      clinical and epidemiological data. The results of the simulation are interpreted
      as representative for cancer of the oral cavity. Basing on the different system
      model outputs, mortality with and without screening, effect on life expectancy of
      the individual and the entire screened population, are discussed. For a screening
      interval of 6 months the increase in life expectancy for a person with cancer of
      the oral cavity is 5.3 years, for the entire population (men older than 40
      years), however, life expectancy increases only by 9.8 days. The proportion of
      patients saved from tumour-associated death rose to 65%. The simulation showed a
      rapidly decreasing effect of the screening programme with longer screening
      intervals. Therefore, a public cancer screening programme is only useful with a
      screening interval of 6 months, and the effect on life expectancy is limited. For
      oropharynx and hypopharynx the possibilities of early stage detection of
      carcinomas are limited and nearly 60% of the cases with carcinoma of the larynx
      are already being treated at an early stage. The importance of public health
      education is emphasised.

PMID- 7802881
TI  - [Differential diagnosis of neck swelling due to suspected metastasis using
      positron emission tomography].
AB  - A noninvasive diagnostic method for the evaluation of a suspicious mass in the
      neck can be of great value for further diagnostic approach. The differing
      metabolic activity of malignant and benign tumors offers the possibility to
      determine the status of a lesion by the quantitative evaluation of the glucose
      uptake by positron emission tomography (PET). The diagnostic relevance of the
      metabolic activity has been shown earlier in more than 50 malignant tumors of the
      head and neck (Reisser et al., HNO 40 [1992] 225-231). The present study
      demonstrates the determination of tumor status in two benign and two malignant
      tumors of the neck by PET. Quantitative evaluation of the glucose uptake revealed
      significantly higher values in malignant than in benign lesions. Therefore the
      determination of the glucose metabolism prior to the indispensable histological
      diagnosis of the status of a lesion can provide valuable hints for the further
      diagnostic and therapeutic approach to the lesion.

PMID- 7802882
TI  - [Detection of human papillomavirus DNA in formalin fixed invasive squamous cell
      carcinoma of the larynx with polymerase chain reaction (PCR)].
AB  - Approximately 67 different subtypes of HPVs have now been described. Regularly
      most of the cervical cancers are positive for HPV 16/18. Current research also
      indicates that HPVs may be involved in the development of benign tumours and also
      squamous cell cancers of head and neck. Studies establishing the presence of
      different HPV subtypes in oral cancers and precancers suggest the possibility of
      the virus as etiological factor in oral carcinogenesis too. In this study the
      prevalence of HPV 6/11, 16 and 18 infection and other exogenous risk factors like
      nicotine and alcohol in laryngeal cancers were studied. A total of 100 formalin
      fixed and paraffin-embedded cancers, 41 glottic and 59 supraglottic, in patients
      aged 58 years, were detected by use of the E6 specific PCR for HPV DNA.
      Significantly more glottic cancers, 26 of 41 (63.4%), were positive for the
      investigated HPV's. HPV 16 was found in all positive cancers. This predominance
      of HPV 16 was also present in the supraglottic carcinomas, but only 10.2% (6 of
      59) of the these groups were HPV positive. In both groups the patients with HPV
      16 and/or 18 positive cancers, the exogenous risk factor was higher than with in
      HPV 16/18 negative tumours. Following infection, the virus either remains dormant
      or else undergoes active replication resulting in the synthesis of infectious
      virus. The integration of virus DNA into the host cell DNA may be the result of
      action of nicotine and/or alcohol. The integration event is the key of the
      carcinogenesis. The level of the risk factor in the patients with supraglottic
      tumours was significantly higher.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7802884
TI  - [A clinically relevant variation of the superior thyroid artery].
AB  - Usually the superior thyroid artery is a branch of the external carotid artery.
      During a functional neck dissection in order to remove a metastasis of a tongue
      cancer we observed a variation of the origin of the vessel that was interesting
      from the surgeon's point of view. The artery rose from the A. carotis communis
      3.5 cm below the bifurcation of the common carotid artery. Normally in this
      region no vessels leave the common carotid artery and therefore the knowledge of
      such variations is important for the exact identification of the neck vessels
      during surgery to avoid a fatal mix-up with the internal carotid artery.

PMID- 7802883
TI  - [Arteria lusoria--a rare cause of dysphagia].
AB  - A rare case of a 29-year old woman with aberrant right subclavian artery (A.
      lusoria) causing dysphagia is presented. This abnormality is generally silent and
      often an incidental x-ray finding. By means of a median thoracotomy the anomalous
      vessel was divided at its point of origin and an anastomosis to the ascending
      aorta with a graft was performed.

PMID- 7802885
TI  - [Microvascular tissue transplantation in plastic reconstruction of the external
      head-neck area].
AB  - Free tissue transfer is under certain circumstances an ideal reconstructive
      method for skin and soft tissue defects of the head and neck region. These are
      multilayer, large defects, recurrences after previous reconstructive methods, in
      cases of aesthetic disturbances due to local flaps, in difficult reconstructive
      areas due to chronic infection and radiotherapy and if local tissue is not
      available. From 1987 to 1993 we performed 30 reconstructions of the surface of
      the head and neck region with free flaps, mainly the forearm flap and the
      scapular flap. But also the latissimus dorsi flap and in one case the rectus
      abdominis flap were used. There was no flap failure. In only one case of a
      forearm flap we saw a delayed healing of the donor defect. There was no
      functional impairment of the donor defect. All cosmetical results were
      acceptable. Flaps from the trunk mainly showed considerable differences in colour
      and texture to the surrounding skin.

PMID- 7802886
TI  - [Noninvasive assessment of intracochlear pressure and patency of the cochlear
      aqueduct in normal probands with TMD (tympanic membrane displacement) analysis].
AB  - The intracochlear pressure cannot yet be evaluated in patients with certain
      audiological neuro-otological diseases. However, it seems to be of importance in
      the diagnosis and pathogenesis of Meniere's disease and related disorders. The
      present paper is aimed at introducing a setup to indirectly assess intracochlear
      and intracranial pressure changes and the design and philosophy of this
      technique. It is possible to describe a normal range of the measured values in
      healthy controls although large interindividual variations occur. In addition,
      the positional changes of the registered parameters enable assessment of the
      patency of the cochlear aquaeduct. This seems to be important in some diseases,
      such as stapes gusher.

PMID- 7802887
TI  - [True and artificial leeches and their use in otology. Images from the history of
      otorhinolaryngology, presented with instruments from the Ingolstadt German
      Medical History Museum collection].
AB  - Based on the concepts of humoral pathology in former centuries bloodletting was
      used as remedy to great extent, systematically by puncturing a vein or locally by
      scarification and cupping glasses. In the 18th and 19th century leeches were
      introduced and applied in huge numbers to cure all conceivable affections
      including diseases of the ear. J. M. G. Itard in Paris in 1821 for treating
      various types of hearing disorders recommended to place leeches at the anus or in
      the nose to imitate bleeding of haemorrhoids or nose-bleeds, which were
      considered natural resources of the body to cope with disorders of the humours.
      H. Schwartze in Halle in 1885 still followed this suggestion. W. R. Wilde in
      Dublin in 1842 and A. F. von Troltsch in Wurzburg 1867 advocated local blood
      letting by leeches around the external ear. The surgeon Ch. L. St. Heurteloup in
      Paris 1840 invented an artificial leech, which was soon widely used in otology
      and ophthalmology. After the first World War the application of leeches became
      obsolete. The humoral pathology had found new approaches: immunology including
      stimulation of the inherent bodily means of defence, and rheology, particularly
      haemodilution. The historical development and the technique of applying live and
      artificial leeches in otology are described in detail.

PMID- 7802888
TI  - [65th Annual Meeting of the German ENT, Head and Neck Surgery Society. Cochlear
      implant].

PMID- 7802889
TI  - [Renewed deviation of the septum after surgery of the nasal septum with
      correction of the external nose (septo-rhinoplasty). 1985 medical malpractice
      procedures settled outside the court].

PMID- 7802890
TI  - [The risk of anesthesia in bronchopulmonary diseases].
AB  - Surgery and anaesthesia, including positioning and mechanical ventilation,
      encompass alterations in respiratory mechanics and gas exchange persisting
      through the postoperative period and may cause respiratory complications. The
      closer the anatomical ties between the surgical site and the respiratory system,
      the higher the pulmonary risks. Pre-existing respiratory and pulmonary diseases
      further increase the patient's risk. In addition to the numerous patients
      suffering from chronic obstructive pulmonary disease, patients with restrictive
      disorders, e.g. obesity, are concerned as well. Arterial oxygen saturation
      tracked by pulse oximetry is recommended for screening the respiratory system.
      Patients at an increased risk of respiratory complications should be scheduled
      individually for preoperative preparation, anaesthesia requirements, and
      postoperative management. When anaesthetizing patients with coexisting pulmonary
      disease, regional anaesthesia is preferred unless limited by the surgical
      procedure or for obvious technical reasons. Pasch provides recommendations for
      the management of anesthesia: Acute respiratory obstruction should be prevented
      by personal attention and pharmacological protection. Anaesthetics and relaxants
      with parasympathomimetic and histamine liberating effects should be avoided.
      Attention should be paid to hazardous pharmacological interactions with existing
      respiratory therapy. Bronchospasm should be avoided by deep anaesthesia and by
      smooth intubation and extubation. Pain therapy is an essential requirement for
      respiratory therapy in the postoperative period to maintain or to restore
      pulmonary function with improved performance.

PMID- 7802891
TI  - [Detection of Chlamydia pneumoniae in intrathoracic abscesses--a case report].
AB  - The case of a 52-year-old patient with intrathoracic abscesses following a
      traumatic fracture of the 11th thoracic vertebral body is described. The
      abscesses were resistant to conventional antibiotic therapy and attempts at local
      drainage under CT scan control remained unsuccessful. Finally, chlamydia
      pneumoniae was isolated using an immunofluorescence technique. Subsequent therapy
      with doxycycline caused complete resolution of the abscesses. We suggest that in
      cases of atypical pneumonias and abscesses, infection with chlamydia pneumoniae
      should be taken into consideration.

PMID- 7802892
TI  - [Acute abdomen--anesthesiologic and intensive care management].
AB  - The expression "acute abdomen" is a provisional destination of a complex of
      various abdominal diseases which require quick diagnostic as well as urgent
      surgical therapy. A close interdisciplinary cooperation during the whole
      perioperative period is of high importance for the prognosis of this potentially
      life-threatening syndrome. The anesthetist must have profound knowledge on causes
      and clinical signs of this disease, on diagnostic measures and on therapeutic
      principles. Anaesthesiological problems arise from the discrepancy between an
      urgent operation on one hand and the necessity of an improvement of the
      preoperative status of the patient on the other. Furthermore, these patients have
      high risks of aspiration due to disturbed motility of the gastrointestinal tract.
      Intensive therapy of these patients is characterized by the peculiarity that a
      primarily local abdominal disease is frequently followed by severe
      extraperitoneal general reactions and multiple organ failure, respectively.

PMID- 7802894
TI  - [The origin of long-distance water supply in the central German area and its
      significance from a hygienic viewpoint].
AB  - By means of the climatic, hydrological and hydrogeological conditions in the
      middle German area the unfavorable water household also due to anthropogenic
      influences caused through mining and industry will be described. These conditions
      have, already in the first half of this century, lead to disadvantages concerning
      the drinking water supply for the population in this territory. Based on older
      ideas for improving the water supply in the middle German area the long-distance
      water supply system Elbaue-Ostharz was built after the 2. world war using the
      water supplies of the river Bode in the Harz, of the Elbaue as well as water from
      the Dubener Heide to overcome the bad water supply situation in middle Germany.
      In this connection the efforts of the public health service for improving the
      drinking water quality in the former country of Sachsen-Anhalt in the DDR will be
      described. Due to an increased connection of the population in the middle German
      area with local central water supplies as well as with the long-distance water
      supply up to 1990 92% of the population could be supplied with drinking water
      from central water supplies. Nevertheless it was not possible to manage all
      problems of drinking water quality up to 1990. These problems concerned local
      central water supplies due to not existing or inadequate plants for water
      refinement in waterworks and poor conditions of the drinking water pipe nets.
      Despite all an increasing improvement of the drinking water could be registered
      as a result of decrease in drinking water consumption, the shutting of water
      works with water catchments on hygienic unfavorable places, the refurbishment of
      water works and the further connection from communes with long-distance water
      supplies. At present and in future too the long-distance water supply will be
      necessary for the middle German area to guarantee a sufficient quantity as well
      as quality of drinking water for the population in this territory.

PMID- 7802893
TI  - [Life threatening tension pneumothorax after puncture of the subclavian vein and
      dislocation of thoracic drainage].
AB  - The combination of two rare complications in intensive care caused an acute life
      threatening situation. Following puncture of the left subclavian vein a
      pneumothorax developed over the course of a couple of days. The inserted thoracic
      drain dislocated into the subcutaneous tissue. During the induction of
      anaesthesia and controlled ventilation a tension pneumothorax developed. A
      decrease in oxygen saturation and an increase in the ventilation pressure led
      first to the diagnosis "malposition of the double lumen endotracheal tube", but
      its correct position could be confirmed by bronchoscopy. Finally, the tension
      pneumothorax was diagnosed by x-ray of the chest. This life-threatening situation
      could be treated by the insertion of a thoracic drain. The operation could be
      performed without any problems.

PMID- 7802896
TI  - [Occurrence and isolation of human enteroviruses from the air of waste removal
      and disposal plants].
AB  - Aerosols from waste treatment plants were examined with regard to the presence of
      airborne viruses. For the purpose of a comparative evaluation, two different
      collecting devices consisting of an electroprecipitator and a special-impinger
      apparatus were used for extraction and collection of viruses from air samples.
      The collected suspensions were concentrated and fractionated by means of
      hydroextraction in combination with a differential centrifugation procedure.
      After solubilisation of the sedimented material with the anionic detergent,
      sodium-dodecylsulfate, and following ultrasonic treatment, viral infectivity
      could be demonstrated in 12 out of 36 examined specimens, after inoculation on
      BGM cells. The highest virus isolation rates were obtained with the
      electroprecipitator. Based on the results of investigations of biological,
      physicochemical as well as antigenic characteristics, the isolated strains
      revealed to belong to the family of Picornaviridae. According to the results of
      additional characterization assays, the isolates were identified as Coxsackie-B
      and ECHO-viruses. The linkage between the occurrence of these viruses and a
      possible risk of infection for humans remains to be elucidated by further
      epidemiological studies. However, the results of the present work indicate that,
      besides of an increased dust and germ concentration in such facilities, there is
      substantial evidence of increased viral contamination as well. Enteroviruses are
      generally considered as indicator viruses revealing the presence of viral
      contaminants in tap water and sewage. As human enteroviruses can be regularly
      isolated from such aerosols, the detection of these viruses in air samples may
      also be an appropriate criterion to estimate the amount to which virus
      concentrations may build up within waste treatment plants.

PMID- 7802895
TI  - [Reduction of bacteria and viruses in purification plant discharges using
      microfiltration in a model plant].
AB  - Microfiltration through a membrane matrix of a nominal pore size of 0.2 microns
      has been applied for advanced treatment of mechanically and biologically treated
      wastewater. Elimination of bacteria and coliphages as well as the decrease in
      some chemical constituents were studied at a flow rate of 80 l/h. Microfiltration
      resulted in a reduction of E. coli, coliform bacteria, fecal streptococci and of
      coliphages by more than 4 logs in the filtrate. Thus, the quality requirements of
      EC Directives for bathing water (EC, 76/160) could be maintained. As a result of
      microfiltration, a 43 +/- 13% removing of the total phosphorous compounds (Pt) in
      the pre-filtered secondary effluent from 11 +/- 2 mmol/m3 (0.34 +/- 0.06 mg/l) to
      6 +/- 2 mmol/m3 (0.19 +/- 0.06 mg/l) was measured. The dosage of FeCl3 (between
      30 and 150 mmol/m3) as coagulant before microfiltration improved the reduction of
      Pt to result in an average value of 75 +/- 16%. After adding FeCl3,
      orthophosphates (PO4-P) could be efficiently reduced by microfiltration. Thus,
      PO4-P concentrations in effluent samples were, in most cases, below the detection
      limit (0.01 mmol/m3).

PMID- 7802897
TI  - [Nosocomial infections with the detection of Staphylococcus aureus in an average
      hospital--an 11-year analysis].
AB  - Nosocomial infections over an 11 years period were monitored prospectively in a
      district hospital. A total of nosocomial infections among 162.197 patients
      discharged from 1980-1990 were analyzed. The incidence rate of nosocomial
      infections was 3.6%. The predominant isolates were Escherichia coli and
      Staphylococcus aureus (11%). The highest rates of S. aureus infections were
      established in wound infections and skin and mucosal infections at surgery,
      gynaecology and paediatrics departments. The number of multiply resistant S.
      aureus strains has decreased and those of sensitive isolates has increased. 72%
      of 652 S. aureus isolates have been typed by phage typing and biotyping.
      Statistical analysis could not establish a significant relationship between phage
      patterns and nosocomial infections. The spectrum of phage patterns of these
      nosocomial strains was the same as those of the endogenous colonization of men.
      Nosocomial outbreaks could not been realized.

PMID- 7802898
TI  - [The microbe colonization of the palatine tonsils of healthy school age
      children].
AB  - In 1988-1992 the tonsillar flora of 1799 children, six years of age and staying
      at certain kindergartens in Bavaria (Bayern), was examined. The microbiological
      investigations, directed at five indicator-germs showed the following results:
      28.6% of the children were carriers of beta-haemolytic Streptococci, 17.4% of
      Enterobacteriaceae and 11.8% of Candida spp., Pseudomonadales and moulds could be
      found in 0.6% of the specimens.

PMID- 7802899
TI  - Antibiotic susceptibility and serotyping of Pseudomonas aeruginosa strains
      isolated from surface waters, thermomineral waters and clinical specimens.
AB  - Different kind of mineral waters used for drinking purposes or hydromineral
      therapy and surface environmental waters for recreational use were tested for the
      presence of Pseudomonas aeruginosa. A comparison of antibiotic resistance
      patterns and serotyping between water strains and P. aeruginosa isolates from
      different infection sites of hospitalized humans (Pisa General Hospital) was
      performed. Altogether one hundred and fifty-six strains were characterized. All
      isolates were most resistant to furans. A very high degree of resistance to
      amoxicillin, clavulanic acid, ampicillin, chloramphenicol, tetracycline and
      trimethoprim was pointed out. Resistance to amikacin, cefotaxime and norfloxacin
      was observed only in strains from clinical specimens. Amikacin was the antibiotic
      to which 80% of multiple resistant strains showed sensitivity. The distribution
      of O-antigen serotypes varied by samples sources; 01, 06, 011 serotypes were the
      most frequently recovered. No isolates were found to be 08, 013, 014, 015
      immunotype. The data indicate that serotyping can be a useful addition to
      antibiotic susceptibility testing for epidemiological purposes.

PMID- 7802900
TI  - [Nosocomial colonization and infection by multiresistant Enterobacter cloacae
      strains on a pediatric oncological unit].
AB  - A multiresistant E. cloacae strain spread during a six month period in a
      paediatric oncology ward amongst nine children, who had different tumors and
      malformations. Three children who had shared a room were especially affected. E.
      cloacae was isolated 122 times from the children with tumors and five times from
      their environment. Specimens from which the bacteria were isolated, included
      blood cultures, catheter tips, wound swabs, drains, skin and mucous membranes
      from most parts of the body. The majority of the E. cloacae strains were
      resistant to ampicillin, mezlocillin, piperacillin, azlocillin, doxycycline and
      cephalosporins of the second and third generation and sensitive to imipenem,
      aminoglycosides and quinolones. The antimicrobial resistance patterns of the E.
      cloacae strains from the paediatric oncology ward were compared to those isolated
      from other wards in the hospital. E. cloacae isolates from the intensive care
      unit had a reduced sensitivity to beta-lactam antibiotics, whereas the isolates
      from the other wards were, with the exception of ampicillin, sensitive to beta
      lactam antibiotics. The analysis of the E. cloacae strains from the paediatric
      oncology ward revealed the same antimicrobial resistance pattern, bacteriocin
      type, RFLP-type and an identical enzyme and whole cell profile. Isolates from
      other wards showed considerably deviating patterns. The systematic registration
      and isolation of patients, colonized or infected with multiresistant E. cloacae
      strains, together with infection control methods, lead to a significant reduction
      in infections.

PMID- 7802901
TI  - [The effect of a short-term SO2 exposure on the respiratory function of
      sensitized non-anesthetized rabbits].
AB  - Exposure to atmospheric pollutants may adversely effect respiratory function.
      Asthmatics as well as persons with airway hyperresponsiveness are more sensitive
      to atmospheric pollutants than normal persons. So we examined the influence of
      bovine serum albumin (BSA) sensitization on changes of respiratory function
      induced by SO2 exposure of 10 min. in non-anesthetized rabbits. Furthermore the
      effect of SO2-exposure on changes of respiratory function induced by secondary
      BSA-sensitization was tested. Respiratory flow (VR), tidal volume (Vt),
      respiratory pressure (PM), respiratory resistance (RL = PM/VR), and dynamic
      Compliance (Cdyn = Vt/PM) were examined. Our data showed that SO2-exposure
      marginally reduced respiratory flow and increased respiratory resistance but did
      not change tidal volume and dynamic compliance. Reduction of respiratory flow
      induced by SO2-exposure was independent from BSA-sensitization in the first week,
      however increase of respiratory resistance was slightly higher in BSA sensitized
      than in non-sensitized rabbits after SO2-treatment. Secondary BSA-sensitization
      reduced respiratory flow independent from SO2-inhalation and increased
      respiratory resistance stronger in SO2 treated than in non-treated rabbits. Tidal
      volume and dynamic compliance also increased after secondary sensitization. The
      increase of dynamic compliance was significantly higher in non-treated than in
      SO2 treated rabbits, but it was not so evident in case of tidal volume.

PMID- 7802902
TI  - [Cohort study of respiratory tract diseases and lung function in school children
      in southwest Germany. 2. Regional influences on respiratory tract diseases in
      Mannheim and the Freiburg area].
AB  - A prospective cohort study on 8124 schoolchildren aged 8 to 16 was conducted
      during the years 1977, 1979 and 1985 in Mannheim and two regions near Freiburg
      (Breisgau and the Black Forest). The objective of this part of the analysis was
      to investigate the regional differences in respiratory symptoms due to air
      pollution. Results are presented of 5726 children who had been living in those
      regions for at least five years at the times of interview. We have analysed 11
      respiratory symptoms and two scores, measuring the tendency to infectious and
      asthmatic diseases, by logistic regression. Comparing the children living 1977 in
      Mannheim or the Breisgau to those living in the Black Forest the Relative Risks
      (Odds Ratios) of respiratory symptoms are in the range of 1.26-1.85 and 1.21-1.96
      respectively. The results for the year 1979 are similar. In 1985 the regional
      effect has become smaller and no difference can be observed between Breisgau and
      the Black Forest. The infect score comprises bronchitis, inflamed throat with
      fever and sinusitis. The Relative Risk of an increased score decreases from 1.67
      in 1977 to 1.65 in 1979 and 1.35 in 1985 in Mannheim and from 1.40 to 1.28 and
      1.05 respectively in the Breisgau. The results of asthma and asthma symptoms are
      not homogeneous. In the Breisgau 1977 and 1979 the Relative Risk of an increased
      asthma score is slightly higher compared to the Black Forest. Allergies of the
      skin are reported more often in Mannheim than in the other areas. The Relative
      Risks of infectious respiratory symptoms and diseases agree spatially and
      temporarily well with the pattern of SO2 concentration. SO2 may be interpreted as
      an indicator for air pollution by power plants, industry and domestic heating.

PMID- 7802903
TI  - [The importance of formic acid excretion in the urine for environmental and
      occupational medicine questions].
AB  - The suitability of the formic acid excretion in the urine as a parameter for the
      biological monitoring of inhalational exposure to formaldehyde is discussed
      controversially. We investigated persons not occupationally exposed to
      formaldehyde (n = 70) to determine possible influencing factors on the
      physiological excretion of formic acid. Following this we carried out a study on
      medical students (n = 30), who during an anatomical dissection course were
      exposed to a short but intensive inhalational exposure to formaldehyde, as well
      as investigations on employees of a pathological-anatomical laboratory (n = 8) in
      order to observe the course of the formic acid excretion in the urine during a
      working week with a continuous exposure to formaldehyde below or within the range
      of the MAK value (0.5 ppm). It was seen that the formic acid excretion in the
      urine with non-exposed persons is subject to considerable inter and
      intraindividual fluctuations (at a maximum by a factor of 30). In addition to
      differences in the endogenous formation of formates an important influencing
      factor is probably the uptake of food containing formic acid or its precursors. A
      value of 23 mg formic acid/g creatinine is given as the upper norm level (95th
      percentile) of adults. In the groups who were exposed to formaldehyde, in some
      cases considerably above the MAK value, we were able to detect no significant
      increase in the formic acid concentration in the urine. After a short but
      intensive exposure to formaldehyde (0.32-3.48 ppm) the formic acid concentration
      in the urine did not change significantly with an average formic acid
      concentration in the urine before exposure of 6.5 mg/g creatinine (central 50%
      range: 3.5-14.2 mg/g creat.) and after exposure of 6.0 mg/g creatinine (central
      50% range: 4.4-10.9 mg/g creat.). There was no significant relationship between
      the individual change in the formic acid concentration in the urine (in mg/g
      creatinine) and the inhalational exposure to formaldehyde determined through
      personal air sampling (r = 0.079). In the course of a working week with a
      continuous exposure to formaldehyde (0.03-0.83 ppm) there was after relating the
      values to creatinine a continuous increase in the median to 22.3 mg/g creat. with
      a starting value of 8.7 mg/g creat. The change proved, however, for the number of
      cases investigated not to be significant. In particular there was no linear
      correlation detectable between the individual changes in the formic acid
      excretion in the urine and the formaldehyde concentrations in the breathing zone
      determined by personal air sampling.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7802904
TI  - Chemical, bacteriological and biological examination and evaluation of sediments
      from drinking water reservoirs--results from the first sampling phase.
AB  - Between September 1992 and April 1993, samples of sediment were taken from a
      total of 16 drinking water reservoirs from seven water suppliers. Five different
      types of raw water were examined, samples being taken with varying frequency. The
      comparison of surface reservoir water and ground water constituted a central aim
      in this first series of investigations. The composition of the sediment was
      determined in terms of its chemical, bacteriological and biological
      characteristics. It was established that the deposits that normally accumulate in
      the course of an operating period contain, in addition to the familiar mass
      determinant inorganic constituents such as iron, manganese and calcium compounds,
      in some cases considerable quantities of organic substances. Total organic carbon
      (TOC) contents of up to 11 weight-% were found. Besides an increased
      concentration of heavy metals, in particular cadmium, nickel and zinc, were
      measured in some sediments. The bacteriological examination of the sediments, in
      accordance with the German drinking water regulation (TrinkwV) showed, in part,
      very high colony counts. However, there was apparently no influence on the
      effluent water as the reservoir was emptied. The microscopical examination showed
      independent of the raw water source the sediments being colonized by
      invertebrates. Up to 9000 organisms per litre of fresh sediment were recorded.
      The predominant group of animals, in terms of numbers, was the rotifers followed
      by threadworms. The comparison of water from impounding reservoirs and ground
      water made evident that the presence of organisms in reservoir sediments is not
      restricted to the use of surface water.

PMID- 7802905
TI  - [Experiences with optimized methods for the detection of legionellae in drinking
      water].
AB  - Entry of Legionellae into domestic water systems by passing through the drinking
      water distribution network has been assumed. To prove this question, samples were
      collected within a two years period at warm and cold water taps of households,
      the pipeline network and three water works of the city of Mainz, and examined for
      the presence of Legionellae. To detect even very small numbers of Legionellae,
      improvement of the conventional isolation procedure was necessary. Additionally,
      large volumes of cold water samples (50-250 L) were processed by using a pressure
      filter. For identification of Legionellae, an immunological rapid test (colony
      blot-assay, own development) and a commercial gene-probe test (EnvironAmp
      Legionella Kits, Applied Biosystems) were enclosed in the programme. With the
      refined techniques the detection limit was improved while expenses of time and
      labour were reduced. Finally, the advantages and disadvantages of the single
      methods are discussed. For routine detection of Legionellae in the
      microbiological laboratory, a combination of effective methods is proposed which
      are easy to perform.

PMID- 7802906
TI  - [Further studies on the falsification of the steam resistance of bioindicators by
      superheating].
AB  - As a supplement to a preceding paper (Zbl. Hyg., 194 (1993). 369-279) the
      resistance of bioindicators has been investigated which differed only in the
      material of which the carriers are made (filter paper and glass fibre fleece,
      respectively). The conditions of the tests were such that further evidence could
      be expected for the fact that the characteristic values of bioindicators can be
      falsified by superheating of the carrier and its envelope. As a test organism
      Enterococcus faecium has been used. To avoid side effects, the bacteria have been
      dried on to the carriers from a suspension in water distillators. The exposition
      basket of the resistometer has been loaded with 3 rows of 15 indicators (disc
      shaped; diameter: 6 mm), arranged parallel. At a temperature of 68 degrees C the
      dependency of (relative) frequency of indicators having surviving test organisms
      capable of multiplying on exposure time to saturated steam has been determined.
      Free exposed indicators made of filter paper required considerably longer
      exposure periods than indicators made of glass fibre fleece to change from
      "(nearly) all the indicators have test organisms capable of multiplying" to
      "(nearly) all the indicators are free from test organisms capable of
      multiplying". The exposure time to free 50% of carriers made of filter paper from
      test organisms capable of multiplying (t50%) amounted to 44.1 minutes. The
      frequency of indicators free from test organisms was higher at the ends than in
      the middle of the exposed rows. When such indicators had been wetted before
      exposure, they showed a t50% value of 2.3 minutes, and the frequency of
      indicators free from surviving test organisms was distributed over the exposed
      indicators evenly. Free exposed indicators made of glass fibre fleece showed a
      t50% value of 4.4 minutes. The frequency of indicators free from test organisms
      was evenly distributed. Wetting of the indicators before exposure changed t50%
      value only slightly. When indicators made of glass fibre fleece had been exposed
      between two layers of filter paper they showed a very high t50% value (47.5
      minutes), and the frequency of indicators free from test organisms was unevenly
      distributed. Indicators being sterile could be found mainly at the ends of the
      exposed rows. In an envelope of parchment paper bioindicators made of glass fibre
      fleece showed considerably higher characteristic values than when free exposed.
      Superheating of the carriers amounted to about 3 Kelvin.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 7802907
TI  - The effect of dentin primer on the tensile bond strength to human enamel.
AB  - Four third-generation dentin bonding products (Scotchbond Multi-Purpose,
      Optibond, All-Bond 2, and Prisma Universal Bond 3) were tested to evaluate their
      tensile bond strength to enamel. Test enamel specimens were etched, primed, and
      polymerized according to each manufacturer's directions. Control specimens were
      treated identically except the primer application was eliminated. The results
      demonstrated that the dentin primer significantly increased the tensile bond
      strength of All-Bond 2, significantly decreased the tensile bond strength of
      Scotchbond Multi-Purpose and Optibond, and had no significant effect for Prisma
      Universal Bond 3. A one-way analysis of variance was run between the eight groups
      tested, and three significant subsets were found (P < .05). The subset with the
      highest mean tensile bond strengths consisted of Prisma Universal Bond 3 primed
      and nonprimed, All-Bond 2 primed, and Optibond nonprimed.

PMID- 7802908
TI  - An analysis of selected normative tooth proportions.
AB  - This study was conducted to determine the average dimensions of the six maxillary
      anterior teeth in a targeted population and to evaluate the relationships between
      intertooth and intratooth dimensions. Casts were obtained from 54 patients
      ranging in age from 18 to 35. Measurements of length and width were made on the
      casts using a digital caliper. Using these measurements, ratios were calculated:
      length to width, width to width, and length to length. Although the tooth
      dimensions varied somewhat by race and gender, the ratios were quite consistent.
      In addition, the golden proportion was not found to correlate with any of the
      calculated ratios.

PMID- 7802909
TI  - Immersion disinfection of irreversible hydrocolloid impressions. Part 1:
      Microbiology.
AB  - This study evaluated the effectiveness of four disinfectants for irreversible
      hydrocolloid impressions. Impressions were made of a sterile metal model of the
      maxillary arch that had been contaminated with one of the following bacteria:
      Staphylococcus aureus, Salmonella choleraesuis, Pseudomonas aeruginosa,
      Mycobacterium bovis, or Bacillus subtilis. The impressions were cultured before
      and after immersion in one of the following disinfectants: lodofive, OMC II,
      0.525% sodium hypochlorite, or Alcide LD. Alcide LD achieved a 4-log10 (99.99%)
      or greater reduction in colony forming units for all five organisms plus mixed
      oral flora. Sodium hypochlorite achieved a 4-log10 reduction in three of the five
      organisms and mixed oral flora. Iodofive and OMC II were ineffective against all
      test organisms and mixed oral flora.

PMID- 7802910
TI  - Immersion disinfection of irreversible hydrocolloid impressions. Part 2: Effects
      on gypsum casts.
AB  - This study evaluated the quality of gypsum casts recovered from disinfected
      irreversible hydrocolloid impressions. Four disinfectants were evaluated: 0.525%
      sodium hypochlorite, Alcide LD, Iodofive, and OMC II. Water served as the
      control. Specimens were evaluated for roughness, surface detail, and dimensional
      stability. Impressions disinfected with NaOCI or Alcide produced gypsum casts
      with physical properties that were generally equal or superior to casts from
      impressions rinsed with water. OMC II and Iodofive generally produced casts
      inferior to the controls.

PMID- 7802911
TI  - The CELAY system: a comparison of the fit of direct and indirect fabrication
      techniques.
AB  - CELAY is a machinable ceramic system that is capable of milling inlays, onlays,
      and veneers from prefabricated industrial ceramic blocks. Direct intraoral or
      indirect patterns may be used to make ceramic restorations. Scanning electron
      microscopy was used to analyze the marginal gap of restorations obtained with
      both methods. The direct fabrication technique yielded significantly better
      marginal gap sizes (P < .01) for the interproximal areas, while with the indirect
      (P < .01) fabrication technique the restorations showed significantly smaller
      marginal gaps at the occlusal borders. The clinical relevance of these findings
      and their possible applications for the development of a new impression material
      are discussed.

PMID- 7802912
TI  - Marginal fit of machine-milled titanium and cast titanium single crowns.
AB  - Eighteen type IV dental stone dies were fabricated from a metal master die that
      replicated a tooth prepared to receive a metal ceramic crown. They were divided
      into three groups according to the type of crowns to be made: (a) machine-milled,
      spark-eroded titanium crowns (Procera); (b) cast titanium crowns; and (c) noble
      alloy crowns (as the control). The control specimens showed the smallest mean
      marginal openings at 25 microns and were significantly different from both the
      machine-milled crowns (54 microns) and the cast titanium crowns (60 microns). The
      two types of titanium crowns were not significantly different from each other.

PMID- 7802913
TI  - Ten-year longitudinal study of masticatory function in edentulous patients
      treated with fixed complete dentures on osseointegrated implants.
AB  - Twenty-three edentulous patients who had been treated with a mandibular fixed
      complete denture retained by osseointegrated implants were followed over a 10
      year period. Nine of these patients had received a maxillary fixed implant
      supported complete denture prosthesis after the initial placement of the
      mandibular restoration, while the remainder still used a conventional maxillary
      complete denture. The maximal occlusal force or mastication efficiency index of
      those having fixed implant-supported prostheses in both arches did not differ
      markedly from those having only a mandibular restoration. However, at the 3-year
      examination, lower values were recorded for the self-rated masticatory ability,
      while higher values were given after 10 years. It was concluded that placement of
      a mandibular fixed implant-supported prosthesis in dissatisfied complete denture
      wearers led to a dramatic improvement of masticatory function that was quite
      acceptable for many patients. However, some patients subsequently demanded a
      maxillary fixed prosthesis to feel satisfactorily rehabilitated.

PMID- 7802914
TI  - Age-related change of masticatory function in complete denture wearers:
      evaluation by a sieving method with peanuts and a food intake questionnaire
      method.
AB  - Age-related changes in masticatory function were investigated in complete denture
      wearers. The sieving method using peanuts as a test food was compared with the
      result obtained using a food questionnaire for evaluation of masticatory
      function. In relationship to aging, both the masticatory performance and the
      chewing score decreased significantly (the masticatory performance: r = .60, P <
      .01; the mastication score: r = -.46, P < .05). It is suggested that the
      masticatory function in complete denture wearers decreases in relationship to
      aging. The food intake questionnaire is useful for evaluating masticatory
      function in complete denture wearers.

PMID- 7802915
TI  - The effect of film thickness on the bond strength of polycarboxylate cement.
AB  - This study examined the bond strength of polycarboxylate cement when used to
      cement gold alloy specimens to dentin. The film thickness was controlled and
      varied over a range of 10 to 150 microns. Tensile and shear bond strengths were
      measured and, contrary to anticipated results, there was an increase in bond
      strength as the film thickness increased. In this study, the bond strength of
      polycarboxylate cement as it relates to film thickness is evaluated in
      relationship to the clinically significant value of 50 microns over the thickness
      range of 150 microns.

PMID- 7802916
TI  - Marginal accuracy of provisional restorations fabricated by different techniques.
AB  - Provisional restorations were fabricated on a cast metal model and the resulting
      marginal discrepancies were measured. In the control group, the restorations were
      fabricated directly on the die and no coolant was applied. Five other methods of
      fabricating provisional restorations were evaluated. The mean marginal
      discrepancies were as follows: Control = 0.228 mm, In Situ (control plus coolant)
      = 0.196 mm, Removal (removed from die to polymerize) = 0.403 mm, On/Off (repeated
      removal/replacement) = 0.601 mm, Reline = 0.074 mm, and Indirect = 0.161 mm. The
      mean marginal discrepancy for the On/Off technique was significantly greater than
      that for all other techniques. The mean marginal discrepancy with the Removal
      technique was significantly greater than that with the Control, In Situ, Reline,
      and Indirect techniques. No significant differences were found between the
      Control, In Situ, Reline, and Indirect techniques.

PMID- 7802917
TI  - Effects of Candida treatment regimens on the physical properties of denture
      resins.
AB  - Denture stomatitis affects approximately 65% of all denture wearers and Candida
      albicans has been established as a primary etiologic agent. Treatment of the
      condition necessitates removal of the organism from denture resins by soaking in
      cleansing/disinfecting solutions. These solutions can have deleterious effects on
      denture resins. Physical properties (flexure strength and surface hardness) of
      heat- and light-polymerized denture resins (Lucitone Pink and Triad) were
      evaluated after candidal colonization and candidal treatment regimens. Light
      activated resins may be the materials of choice for patients prone to denture
      stomatitis, as they have demonstrated less overall degradation from candidal
      treatment modalities.

PMID- 7802918
TI  - Environmental factors affecting mechanical properties of facial prosthetic
      elastomers.
AB  - This study evaluated the degradation of elastomers for facial prostheses exposed
      to environmental factors normally present in a service environment. Two silicone
      elastomers and a polyurethane were evaluated. Samples were exposed to ultraviolet
      radiation, simulated sebum, ozone, chlorine, and nitrogen dioxide, and tested for
      tear propagation and resistance. Test results revealed significant differences in
      the tear characteristics between silicones and polyurethane. Differences in tear
      patterns were observed between the control and the specimens exposed to
      environmental factors. The environmental factors affected the polyurethane
      Epithane-3 the most and silicone MDX 4-4210 the least. When exposed to chlorine
      and nitrogen dioxide, Cosmesil and Epithane-3 were degraded to a point where
      sample testing was not possible. When exposed to ultraviolet radiation, Epithane
      3 was degraded and could not be tested. Simulated sebum and ozone affected
      Cosmesil and Epithane-3, but no clear trends were observed.

PMID- 7802919
TI  - The syntax of immune-neuroendocrine communication.
AB  - There is now overwhelming evidence that cytokines, peptide hormones and
      neurotransmitters, as well as their receptors, are endogenous to the brain,
      endocrine and immune systems. Here, Edwin Blalock discusses how these shared
      ligands and receptors are used as a common chemical language for communication
      within and between the immune and neuroendocrine systems. Such communication
      suggests an immunoregulatory role for the brain and a sensory function for the
      immune system. A clearer understanding of this circuitry is dramatically altering
      our understanding of physiology and may profoundly affect the treatment of human
      disease.

PMID- 7802920
TI  - The influence of neuroendocrine pathways on lymphocyte migration.
AB  - The immunological work that leads to the production of effector cells,
      immunoglobulins and cytokines in intact animals results from the coordinated
      interaction of clusters of specialized lymphocytes. These lymphoid clusters
      function in microenvironments within which they may be exposed to neural and
      endocrine signals, and the ability of such signals to modulate the local output
      of immune labor is now well recognized. Here, Clifford Ottaway and Alan Husband
      review evidence suggesting that the output of neuroendocrine pathways has a
      modulatory effect on the migratory behavior of lymphocytes in vivo. This can lead
      to rapid changes in the specific phenotypes of lymphocytes accumulating in
      tissues and organs undergoing immune challenge.

PMID- 7802921
TI  - Control of thymus physiology by peptidic hormones and neuropeptides.
AB  - Several immune-neuroendocrine interactions are known to occur both in primary and
      secondary lymphoid organs. Here, Mireille Dardenne and Wilson Savino review data
      obtained in humans and experimental animals showing that peptidic hormones and
      neuropeptides can influence the thymus pleiotropically. These mediators modulate
      thymic epithelial cells (TECs), affecting thymulin secretion, cytokeratin
      expression, production of extracellular matrix (ECM) proteins and cell growth.
      Interestingly, such neuroendocrine influences appear to be part of a
      bidirectional circuitry, since thymic-derived peptides also regulate the release
      of hormones from the pituitary and hypothalamus.

PMID- 7802922
TI  - Prolactin and early T-cell development in embryonic chicken.
AB  - Currently, the information available on the ontogeny of the immune-neuroendocrine
      network is somewhat scant. However, increasing data suggest a role for prolactin,
      an important immunoregulatory molecule that resembles cytokines, in early T-cell
      development. In this article, Javier Moreno and colleagues present evidence for
      this role using the chicken embryo as a model system.

PMID- 7802923
TI  - Neuroendocrine regulation of inflammation and tissue repair by submandibular
      gland factors.
AB  - Interactions between the immune, nervous and endocrine systems are important in
      inflammation and tissue repair. One neuroendocrine pathway involves polypeptide
      factors derived from the submandibular glands, whose synthesis and release are
      controlled by cervical sympathetic nerves. This novel pathway of immune
      neuroendocrine communication is the cervical sympathetic trunk-submandibular
      gland (CST-SMG) axis. Here, Ronald Mathison, Joseph Davison and Dean Befus
      discuss the contributions of this axis to the neuroendocrine regulation of
      inflammation and tissue repair.

PMID- 7802924
TI  - The interaction between mast cells and nerves in the gastrointestinal tract.
AB  - Study of the neuroimmune system typifies the new integrative approach to
      biological systems. Numerous spatial associations between mast cells and nerves
      have been described, and data are accumulating on the functional aspects of this
      relationship. Here, Derek McKay and John Bienenstock review the bidirectional
      communication between mast cells and nerves as a homeostatic unit in the
      regulation of gut physiology and host defense.

PMID- 7802925
TI  - Pregnancy: a clue to normal regulation of B lymphopoiesis.
AB  - The large-scale production of lymphocytes in the bone marrow reflects a delicate
      balance between positive and negative regulatory signals. For instance,
      interleukin 7 (IL-7) provides a positive signal, and appears to be both essential
      and limiting in the mouse. However, much less is understood concerning the
      negative molecular signals that may limit the output of lymphocytes. Here, Paul
      Kincade and colleagues discuss how a chance observation with pregnant mice
      revealed that sex steroids can act as negative regulators of B lymphopoiesis, and
      may do so under normal steady-state conditions.

PMID- 7802926
TI  - The thymus in pregnancy: the interplay of neural, endocrine and immune
      influences.
AB  - This article discusses the dramatic events that accompany thymic involution
      during pregnancy, and traces the possible immune, neural and endocrine
      interactions that may occur. Ann Clarke and Marion Kendall present accumulating
      evidence that activity, not inactivity, is a feature of the thymus at this time.
      Whilst the cortex shrinks, the medulla enlarges and rearranges to create a
      microenvironment containing increased numbers of mature thymocytes. It is
      suggested that these recently derived T cells may contribute to the unique
      populations of cells with suppressive function that appear during pregnancy, and
      thereby contribute to the immune suppression of the mother to paternal and fetal
      antigens. In addition, the pregnancy-associated cortical involution of the thymus
      may reflect the deletion of clones with potential reactivity to paternal and/or
      fetal antigens.

PMID- 7802927
TI  - [Adhesion molecules and inflammatory dermatoses].
AB  - In inflammatory dermatoses, adhesion molecules are involved in the interaction of
      leukocytes with endothelial cells, extra-cellular matrix and epidermal cells. In
      dermatosis where epidermal cells are the main targets of inflammation, the
      keratinocytes are activated and participate to the local immune reaction through
      the secretion of cytokines and the expression of the adhesion molecule ICAM-1 and
      the HLA-DR antigens. Induction of ICAM-1 by IFN gamma or TNF alpha on
      keratinocytes that do not express this molecule in normal skin may account for
      the recruitment of T cells into the epidermis. In the dermis, an up-regulation of
      ICAM-1 expression occurs on endothelial cells activated by cytokines (IL-1, TNF
      alpha...) and is usually correlated with an induction of ELAM-1 and less
      frequently VCAM-1. These adhesion molecules are involved in the recruitment of
      inflammatory cells but also in the control of their retention and migration
      through the skin.

PMID- 7802928
TI  - [Role of adhesion molecules in bronchial inflammation and bronchial
      hyperreactivity].
AB  - Adhesion molecules are glycoproteins situated in the cell membrane. These
      molecules permit cells to integrate specifically with the specific cellular
      receptors or ligands and with the extracellular matrix during intra-tissular
      migration. Structurally, 4 large families can be distinguished: the
      immunoglobulin family, the integrins, the selectines, and finally the cadherines.
      The results of preliminary studies in man seem to confirm those obtained in vivo
      and in vitro in animals. The in vitro studies have shown that overall the
      inflammatory cells, such as the eosinophils as well as the endothelial and
      epithelial cells have many adhesion molecules, the regulation of which is
      dependent on many cytokinetic mediators, such as interleukin 1 beta (IA-1 beta),
      tumour necrosis factor (TNF alpha) and interleukin 4 (IL4). In man, it has been
      observed that there is a significant increase in TNF alpha in the bronchial
      mucosae of asthmatics. Together, the experimental studies have shown the crucial
      role of adhesion molecules in specific recruitment and their regulation by
      cytokines in the physiopathology of bronchial inflammation and hyper-reactivity
      that are characteristic of asthmatic disease.

PMID- 7802929
TI  - [The ICAM-1 cell adhesion molecule in asthma and atopic dermatitis].
AB  - Measurement of serum ICAM 1, an adhesion molecule, by an enzymo-immunological
      method, compared with IgE and IFN gamma in three groups of subjects (reference,
      asthma and atopic dermatitis) shows a statistically significant raised titre in
      the atopic dermatitis group (377 ng/ml) in comparison with the reference group
      (300.4 ng/ml). The titre of ICAM 1 in the asthma group (317 ng/ml) was not
      significantly different from that of the reference. The difference between the
      latter two groups may be more clearly seen if the measurements were made not in
      serum but instead in the liquid from broncho-alveolar lavage (LBA) for
      asthmatics.

PMID- 7802930
TI  - Prilotest, an innovative disposable skin puncture test: qualitative aspects.
AB  - Prilotest is a new disposable skin puncture test that has been recently produced
      and marketed by Laboratorio Farmaceutico Lofarma, Milan-Italy. The tip of the
      device is submerged in a well containing the allergen extract. As a result, the
      product is ready for use and there is no longer a need to place a drop of the
      allergen extract on the skin beforehand. Thus, the diagnostic procedure is
      simplified, the test offers excellent reproducibility. We made a comparative test
      of the reproducibility of the new method and Pepys' modified prick test on thirty
      patients (10 sensitized to Grass pollen, 10 to Pellitory pollen, and 10 to house
      dust mites); each test was repeated eight times. We also evaluated the
      specificity and sensitivity of the new method in 39 different allergic patients
      (13 sensitized to Grass pollen, 13 to Pellitory pollen, and 13 to house dust
      mites) and in 39 healthy subjects. The results show that the new method has a
      significantly higher level of reproducibility than Pepys' modified prick test.
      Furthermore, the reproducibility obtained is higher than results reported in
      literature for various standardized prick test methods. The sensitivity and
      specificity of the new method was excellent.

PMID- 7802931
TI  - [The pork-cat syndrome: effect of sensitization to cats on sensitization to pork
      meat. Apropos of a case].
AB  - A patient who presented with exercise-induced anaphylaxis, linked with a food
      allergy to pork meat (VP), about three years ago became allergic to VP though
      effort was necessary to trigger the anaphylactic reactions. These disappeared
      after suppression of the VP allergy, but the IgE response to VP persisted until
      the cat was removed from the environment.

PMID- 7802932
TI  - Lignin-carbohydrate complexes in forages: structure and consequences in the
      ruminal degradation of cell-wall carbohydrates.
AB  - Lignin-carbohydrate complexes (LCCs) are recognised as key structures in forage
      degradability. Apart from ester bonds involving phenolic acids, which seem to
      play a major role in grasses, little is known about the other types of linkages
      that must exist but have proved difficult to demonstrate. The chemical nature of
      possible LCC linkages is presented and the various mechanisms through which LCCs
      in the cell-wall architecture may interfere with carbohydrate utilisation by
      rumen microorganisms are discussed.

PMID- 7802933
TI  - [Methods of analysis relating to blood flow measurement of the viscera and aorta
      in sheep].
AB  - Two methods of analysis of blood flow data are presented. They are aimed at
      reducing: 1) the methodological variability associated with splanchnic blood
      flows measured by dilution (PAH) and 2) the variability of aortic blood flows
      measured ultrasonically associated with physical activity. Six multicatheterized
      ewes were used; they were first fed at maintenance and then at half-maintenance.
      Observed splanchnic blood flows were very variable when PAH was infused in
      mesenteric vein only (average CV = 17%). Variability was first reduced by a PAH
      infusion via both a mesenteric and a ruminal vein (CV = 11%), second by rigorous
      corrections on instantaneous blood flow data (CV = 13.5%), or by a combination of
      both (CV = 9.5%). Corrections did not modify the conclusions of the analysis of
      variance concerning the treatment effect, but reduced the residual variance and
      eliminated the negative hepatic artery blood flow values. At the hindquarters
      level, corrections allowed us to approach the aortic blood flows of animals in a
      similar 'quietly standing' state. They decreased the daily variability (from 22
      to 8%) and enabled the detection of a treatment effect, which was not shown by
      observed data.

PMID- 7802935
TI  - Effect of acrosome defects and sperm chromatin decondensation on fertility and
      litter size in the rabbit. Preliminary electron-microscopic study.
AB  - Sections of ejaculated spermatozoa from rabbits with known fertility were
      observed by transmission electron microscopy. Acrosome defects, odd head shapes,
      the presence of spermatids and the decondensation of sperm nuclei were recorded.
      The fertility negatively correlated with the number of acrosomal defects, while
      litter size was negatively related to nuclear decompaction. Sperm nuclear
      decondensation was present in all ejaculates. Its frequency was correlated with
      that of spermatids in ejaculates.

PMID- 7802934
TI  - Microfilaments, microtubules and intermediate filaments fulfil differential roles
      during gonadotropin-induced expansion of bovine cumulus oophorus.
AB  - The relationship between cytoskeleton and morphology of cumulus granulosa cells
      in expanding bovine oocyte-cumulus complexes (OCCs) cultured in vitro has been
      investigated by the means of indirect immunofluorescence and transmission
      electron microscopy. The round-shaped cells in unstimulated control OCCs
      displayed a homogeneous distribution of cytoskeletal networks and cytoplasmic
      organelles. Luteinizing hormone (LH) stimulation caused the redistribution of
      microfilaments (MFs), accelerated the development of Golgi apparatus, and led to
      the generation of lipid droplets in cumulus cells. These changes culminated in
      the elongation and polarization of cumulus cells and in the extension of the
      cytoplasmic networks of microtubules (MTs) and intermediate filaments (IFs) into
      the newly formed cytoplasmic projections. The culture of OCCs in the presence of
      microfilament disruptor cytochalasin B prevented cumulus expansion, formation of
      cellular projections and cell elongation and suppressed the development of the
      Golgi apparatus. On the contrary, cytochalasin had no effect on the abundance and
      distribution of lipid droplets and on the integrity of IFs and MTs. The present
      data support the hypothesis that the response of cumulus granulosa cells to LH is
      partially mediated by F-actin.

PMID- 7802936
TI  - Effect of calcium and mineral waters on oleic-acid uptake by isolated hamster
      enterocytes.
AB  - The effect of calcium upon the uptake of oleic acid solubilized with 10 mM
      taurocholate was investigated using an in vitro model of isolated enterocytes.
      The addition of Ca2+ to the incubation medium (Hanks' medium) led to a decrease
      in oleic-acid uptake. This uptake inhibition was dependent on both the amount of
      Ca2+ and the fatty-acid concentration, since the inhibitory effect was
      significant for 10 microM but not 100 microM oleic acid. The determination of the
      monomeric activity of oleic acid indicated that the decrease in fatty-acid uptake
      was not linked to the formation of insoluble calcium soaps. The replacement of
      Hank's medium by several mineral waters containing between 0.3 and 11.7 mM Ca2+
      significantly reduced the uptake of both 10 and 100 microM oleic-acid. The ionic
      composition of these waters was correlated with the decrease of initial rate of
      oleic acid uptake, but Ca2+ and other ions could interfere by synergetic effects
      with the fatty-acid-absorption mechanism. It is concluded that the ion-induced
      inhibition of oleic-acid uptake is not due to the formation of insoluble soaps
      but rather to a direct effect on the fatty-acid transport in membranes. Whether
      the fatty-acid binding protein in the plasma membrane is involved in the effect
      of Ca2+ on fatty-acid transport remains to be established.

PMID- 7802937
TI  - Removal of residual yolk at hatch influences food choice and feeding activity in
      lines of chickens selected for high or low juvenile body weight.
AB  - The effect of residual yolk removal at hatch on growth and feeding behavior was
      assessed in lines of chickens divergently selected for low (LW) or high (HW) 56
      day body weight. At hatch chicks were assigned to 1 treatment: removal of the
      residual yolk (R) or no surgery (I). Twenty-four chicks per line (12 I and 12 R)
      were assigned to an all-mash regimen (M) and 48 per line (24 I and 24 R) to a
      choice (C) between mash and dietary residual yolk. HW were heavier than LW chicks
      regardless of treatment. On day 5 and thereafter, chicks given a choice were
      heavier than those eating mash. HW chicks ate more than LW ones. The percentage
      of yolk eaten increased during the 2-3 d after hatch, remained constant for 2 d,
      then decreased. Results are discussed in term of yolk need and development of the
      gastrointestinal tract in the divergent lines.

PMID- 7802938
TI  - Folate deficiency and congenital malformations induced by pyrimethamine in the
      rat.
AB  - In order to establish a relationship between the appearance of congenital
      malformations and the decrease of folic acid in rat mothers and embryos, a folic
      acid antagonist, pyrimethamine (PY), was administered. On the 12th day of
      gestation/pregnant rats received an intraperitoneal injection of 12.5, 15.63,
      18.75 or 25 mg/kg PY. On the 13th day of gestation folic acid was measured in
      different maternal and embryonic tissues obtained after surgical hysterectomy of
      1 uterine horn. On the 21st day of gestation malformations were studied on live
      fetuses remaining in the opposite horn. The folate levels were identical in all
      maternal tissues. The concentration of folic acid significantly decreased (50%)
      within the embryonic tissues in all PY-treated groups. A decrease of fetal weight
      occurred in the 18.75 and 25 mg/kg PY groups. Malformations were observed in the
      same groups. A dysfunction of the placental transfer of folates is hypothesized.

PMID- 7802939
TI  - Preserved bone mass in ovariectomized rats treated with parathyroid-hormone
      related peptide (1-34) and (107-111) fragments.
AB  - The effect of synthetic human PTHrP (1-34) or (107-111) fragments on bone loss
      was studied in rats, one month after ovariectomy (OVX). Four groups of 7-8-month
      old rats were treated sc daily for 13 d with PTHrP (1-34) or (107-111) at the
      dose of 1 or 3 nmol/100 g body weight. Sham-operated (SHO) and control OVX rats
      received solvent alone. In our conditions, at the lowest dose, neither (1-34) nor
      (107-111) fragments had any significant effect. However, at the dose of 3
      nmol/100 g daily for 13 d both treatments significantly increased femoral dry
      weight, ash weight, Ca content and densitometry of the femur. The effect of PTHrP
      (1-34) mainly resulted from increased cortical and trabecular bone (% recovery:
      98.25 and 105.23%, respectively). For the PTHrP (107-111) fragment, a positive
      effect was only demonstrated on the cortical bone (98.25% recovery). The results
      of this study demonstrate that both hPTHrP (1-34) and (107-111, osteostatin)
      fragments are positive for bone when administered at the dose of 3 nmol/100 g
      body weight/d for 13 d to adult OVX rats.

PMID- 7802940
TI  - Degradation in the rumen of proteins of 2 legumes: soybean meal and field pea.
AB  - Ruminal protein degradation of soybean meal and field pea were compared using 2
      analytical methods: in situ and a laboratory analysis with a proteolytic enzyme
      extracted from Streptomyces griseus. The degradation of total nitrogen in nylon
      bags of the feeds was measured between 0 and 48 h in the rumen of 2 cows
      (theoretical degradability: 70.0% for soybean meal and 94.7% for field pea).
      Electrophoresis of proteins of feeds and in situ residues, in sodium dodecyl
      sulfate-polyacrylamide gel (SDS-PAGE) showed that both species have the same type
      of proteins (7S and 11S) which were degraded in a similar manner in the rumen.
      The 7S fraction was degraded rapidly whereas the 11S fraction was more resistant.
      The electrophoretic profiles showed that protein components were less degraded
      after enzymatic than in situ degradation. In the supernatant after enzymatic
      hydrolysis, protein and peptides were found in large concentrations and alpha
      amino nitrogen and ammonia in low concentrations. It was difficult to simulate
      the in vitro activity of enzyme complexes in the rumen and the results must be
      confirmed by direct measurement of the rumen liquid.

PMID- 7802942
TI  - [The theory of differentiation tendency of Chinese medicinal herbs in regional
      habitually used drugs].
AB  - The article puts forward a new point about "the theoretical study of biological
      origins of Chinese herbs". The origin, meaning and reason for emergence of
      "regional habitually used drugs" are discussed and examples of these drugs used
      in history and modern times are given. It is indicated that these drugs are
      gradually differentiated with their species character being made clear. It is
      thus suggested that more efforts be made to study these drugs, promote their
      differentiation and treat them by their character and nature.

PMID- 7802941
TI  - In vitro evaluation of zwitterion buffers in diluents for freezing ram
      spermatozoa.
AB  - Diluents based on the zwitterion buffers Tes, Hepes and Pipes titrated to pH 7.0
      with NaOH or Tris were compared with Tris-citrate diluents by assessment of post
      thawing motility and acrosome integrity of frozen ram spermatozoa. Varying buffer
      osmolalities between 300 and 360 mosmol had no effect but there was a decrease (P
      < 0.001) in motility between 360 and 420 mosmol. There was a quadratic effect (P
      < 0.001) on motility of increasing glucose concentration in the diluent (30, 85,
      140, 195 and 250 mM) with a maximum at 85 mM. At this sugar concentration,
      motility was higher (P < 0.001) for diluents containing glucose and fructose than
      lactose, sucrose or trehalose. Inclusion of egg yolk (optimum at 13.5% v/v; P <
      0.05), centrifugation of the diluents (P < 0.01), use of low dilution rates (3 or
      6-fold; P < 0.05) and freezing in pellets rather than minitubes or straws (P <
      0.001) improved both the motility and acrosome integrity of spermatozoa in the
      zwitterion diluents. It is concluded that zwitterion buffers are superior to Tris
      citrate in ram semen freezing diluents.

PMID- 7802943
TI  - [Conservation of rare and endangered medicinal plants in the Wuyi Mountain Nature
      Reserve].

PMID- 7802945
TI  - [A preliminary pharmacological study of differently processed leech].

PMID- 7802944
TI  - [A comparative study on anti-ulcer action of unprepared and calcined oyster
      shell].
AB  - On experimental gastric ulcer models induced by 0.6mol/L HCl, ethyl alcohol or
      ligation of the pylorus, the preventive effects of unprepared oyster shell,
      calcined oyster shell 1(900 degrees C, 1h), calcined oyster shell 2(350 degrees
      C, 8h) were compared in Wistar rats. Results showed that antagonistic effects of
      calcined oyster shell 1 to the drug pathogenesis of peptic ulcer and the
      incidence of peptic ulcer after ligation of the pylorus were markedly greater.

PMID- 7802946
TI  - [Determination of alkaloids in Evodia rutaecarpa (Juss.) Benth. and its processed
      products by TLC-densitometry].

PMID- 7802947
TI  - [Quality standards of huanglian jiedu pills].
AB  - TLC and microscopy have been used in the qualitative study of Huanglian Jiedu
      Pills. The contents of berberine hydrochloride and baicalin in these Pills have
      been determined. The proposed method can be used to control the quality of
      Huanglian Jiedu Pills.

PMID- 7802948
TI  - [Quantitative analysis of muscone in shexiang baoxin pills by gas
      chromatography].
AB  - By using benzene as the extraction solvent and the method of internal standard,
      Shexiang Baoxin Pills was directly analyzed for muscone by GC. The method showed
      very good stability and linearity. The rate of recovery was 101.4%.

PMID- 7802949
TI  - [Quantitative analysis of synephrine in zhishi injection by RP-HPLC].
AB  - A reversed phase HPLC method was developed for the determination of synephrine in
      Zhishi Injection using methanol-water (1:1) containing sodium 1-pentane sulfonate
      (3.5%, G/V) and acetic acid (0.1%, V/V) as the mobile phase with UV detoction at
      275nm. Linear response was obtained in the range of 8-64 micrograms/ml (r =
      0.9998), the absolute recovery was 96.2-103.4%, and RSD 2.7%-6.0% (n = 7).

PMID- 7802950
TI  - [Chemical constituents of Notopterygium incisum Ting].

PMID- 7802951
TI  - [GC-MS analysis of essential oil from pericarps of Illicium difengpi K.I.B. et
      K.I.M].

PMID- 7802952
TI  - [Determination of hesperidin in Pericarpium Citri Reticulatae by HPLC].
AB  - A HPLC method for the determination of hesperidin in Pericarpium Citri
      Reticulatae has been established in this report. The method is simple, specific
      and accurate. The recovery of hesperidin is 98.3% and relative standard deviation
      0.2%.

PMID- 7802953
TI  - [Pharmacological studies on the effects of huanglian decoction on experimental
      gastric lesions in rats and antiemetic in pigeons].
AB  - The results showed that Huanglion decoction has protective effect on ethanol-,HCl
      and aspirin-induced gastric hemorrhagic lesions in rats and antemetic effect on
      CuSO4-induced vomiting in pigeons. A dose of 27g/(kg.d) po applied in mice showed
      no toxic action. This dose is 400 times that of clinical application.

PMID- 7802954
TI  - [Pharmacological actions of hyphae body of Auricularia auricula (L. ex Hook)
      Underw and its alcoholic extract].
AB  - The percent peripheral blood T lymphocytes were elevated and HC50 reduction
      induced by cyclophosphamide was recovered after the hyphae body of Auricularia
      auricula had been ip administered in mice. The action of blood platelet
      agglutination in rats induced by ADP was inhibited and the time of erythrocytic
      electrophoresis in mice was shortened after the alcoholic extract had been ig
      administered.

PMID- 7802955
TI  - [Pharmacological research on action of xinjing Cistanches deserticola Y.C. Ma on
      free radical injury].

PMID- 7802956
TI  - Morphologic evaluation of the pathogenesis of bacterial enteric infections.
AB  - Current advances in the understanding of the pathogenicity of the agents of
      diarrheal infections, Vibrio cholerae, diarrheagenic E. coli, Shigella,
      Salmonella, and enteropathogenic Yersinia, have, to a great extent, become
      possible due to morphological studies of host-pathogen interactions in natural
      and experimental infections. Despite a multigenic nature and a diversity of
      pathogenic features in the bacterial species and even in serogroups of the same
      species, it is now possible to delineate four major patterns of interaction of
      enteric pathogens with their cellular targets, the enterocytes, and with the
      immune apparatus of the gut. These patterns, epicellular cytotonic, epicellular
      restructuring cytotonic, invasive intraepithelial cytotonic and cytotoxic, and
      invasive transcellular cytotonic and cytotoxic bacteremic, underlie early
      pathogenesis and clinical manifestations in the respective diarrheal diseases. In
      this review, the results of the morphological analyses of these patterns over the
      last 3 decades as well as some methodological problems encountered in the
      interpretation of morphological observations are discussed.

PMID- 7802957
TI  - Fungal plasma membrane proton pumps as promising new antifungal targets.
AB  - Fungi are widely dispersed in nature and frequently appear as pathogens in the
      animal and plant kingdoms. The incidence of opportunistic fungal infections in
      humans has increased due to the human immunodeficiency virus and the application
      of modern medical approaches that subvert natural protective barriers to
      infection. Also, fungal blights continue to threaten crops worldwide. As a
      result, new antifungal agents are needed to address these critical problems.
      Existing antifungals can be used to effectively treat most cases of topical
      infection caused by the opportunistic pathogen Candida albicans, which is the
      principal agent of nosocomially acquired fungal infections. However, life
      threatening, disseminated Candida infections are treated with more modest
      success. Existing antifungals can be toxic or ineffective because of natural
      resistance or even induced resistance. This limited efficacy largely reflects the
      restricted range of cellular targets considered during the development of current
      antifungals. The advancement of highly selective fungicidal reagents requires the
      recognition of new essential cellular targets. The fungal plasma-membrane proton
      pump is a high-abundance essential enzyme with a number of well-understood
      molecular properties that should facilitate the development of new antifungals.
      The proton pump is important for intracellular pH regulation and the maintenance
      of electrochemical proton gradients needed for nutrient uptake. It is a member of
      the P-type class of ion-transport enzymes, which are present in nearly all
      external cellular membranes. Typical P-type enzymes such as the Na+,K(+)-ATPase
      and H+,K(+)-ATPase are well established as specific targets for surface-active
      cardiac glycosides and anti-ulcer therapeutics. The development of new classes of
      selective antifungals targeted to the proton pump will require exploitation of
      the well-characterized genetic, kinetic, topological, regulatory, and drug
      interaction features of the fungal enzyme that discriminate it from related host
      P-type enzymes. New antifungal drugs of this type should be relevant to the
      control of fungal pathogens of medical and agricultural importance and may be
      applicable to the control of intracellular parasites that also depend on closely
      related proton pumps for survival.

PMID- 7802958
TI  - Ecology of free-living amoebae.
AB  - Small free-living amoebae (FLA) are the main predators controlling bacterial
      populations in soils. They are distributed in the rhizospheric zone and the
      surrounding bulk soil; however, they may spread deeper, reaching the vadose zone
      of groundwater systems, especially where bacterial populations get to high
      densities. Soil texture is the physical factor controlling the distribution of
      FLA because it determines the mean bore pore of soil aggregates and other
      important physical factors. FLA help maintain the high bacterial mineralization
      rate of organic matter through predation. As attachment onto a surface is
      necessary for feeding, the quantity of available surfaces is very important for
      developing this activity. However, the role of protozoa on plant growth promotion
      is still unclear because they may increase this effect by feeding on both fungi
      and bacteria. Small FLA are found in soils or sediments, as well as attached to
      suspended particulate matter in water columns, in the first 30 microns of water
      surface, or on the bodies of submerged animals and plants. These microorganisms
      do not distinguish between terrestrial or aquatic environments because they live
      in the interfaces between them. However, their importance in aquatic systems has
      been considered as negligible because they are outcompeted by free swimmers. The
      water conditions affecting amoebae survival are pH, temperature, concentration of
      sulfhydric acid and salinity. These factors have a strong influence on the
      structure of amoebae communities in aquatic environments. FLA are considered
      cosmopolitan as a group, and they live inside vertebrates, in soils, freshwater,
      marine waters, and on the aerial parts of plants and animals. These microbes, are
      spread by wind and water currents. Once in the air, cysts and trophozoites behave
      like any other suspended particulate matter. Therefore, suspension
      transportation, and removal depend on atmospheric dynamics rather than on their
      own mechanisms. Ultraviolet light and drought are the main causes of losing
      viability, but much needs to be learned about the effects of air contaminants on
      amoebal survival. Naked amoebae also live in the phyllosphere as part of
      phylloplane community, but their importance and participation in this environment
      remain unknown. Some species belonging to the genera Acanthamoebae, Naegleria,
      and Balamuthia cause fatal diseases in humans and are carriers of other pathogens
      such as Legionella pneumophilia. However, FLA communities can be of some utility
      in sewage treatment works based in soil filters. FLA's predatory activity in the
      root zone method may be of greater importance than previously thought, because
      this is their natural or more favorable environment.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7802959
TI  - [Society, violence and health].

PMID- 7802960
TI  - [Dietetic factors in epidemic neuropathy on Isla de la Juventud, Cuba].
AB  - The epidemic of neuropathy that arose in Cuba in late 1991 has clinical
      manifestations similar to those of other neuropathies that are nutritional in
      origin. In an effort to identify its possible association with the diet, a case
      control study was conducted at the beginning of the epidemic in Isla de la
      Juventud. Dietary intake was assessed through a semi-quantitative survey of
      consumption frequency obtained by direct personal interviews, and measurements
      were taken of the weight, height and skin fold thickness of 34 cases and 65
      controls. As compared to controls, cases showed more pronounced weight loss prior
      to becoming ill, a lower body mass index (BMI), a lower percentage of body fat,
      and a poorer diet. According to odds ratios (OR) resulting from the separate
      analysis of each variable, factors associated with illness were weight loss, low
      BMI, low weight for height, a lower consumption of bread and rice, a less
      balanced diet, lack of milk intake, an intake of sugar greater than 15% of total
      energy consumed, consumption of alcohol, and smoking. The association was
      protective in the case of beans, tubercles, starchy roots, oil, and meat
      substitutes made from soy. Multifactorial analysis revealed higher OR values,
      adjusted for smoking and alcohol consumption, for intakes of less than 50% of the
      recommended daily allowance of protein, pyridoxine, thiamine, energy, vitamin E,
      niacin, folic acid, fat, riboflavin, and vitamin A. The results of this analysis
      show that tobacco and alcohol promote the effects of a deficient diet, but do not
      in and of themselves explain the association. A global analysis of these results
      leads to the conclusion that a diet poor in energy, calories, fats, and those
      micronutrients that have come under study, and that is unbalanced because of a
      relative excess of sugars, with its resulting effect on body weight, is strongly
      associated with and causally related to epidemic neuropathy.

PMID- 7802961
TI  - [The relationship of the immunodeficiency virus, AIDS and tuberculosis in New
      York City].

PMID- 7802963
TI  - [A technical disagreement].

PMID- 7802962
TI  - [A clarification of the abortion laws in Spain].

PMID- 7802964
TI  - [A decrease in the incidence of infantile diarrhea due to the promotion of breast
      feeding in Mexico].

PMID- 7802965
TI  - Distribution of cholecystokinin binding sites in the North American opossum
      cerebellum.
AB  - Previous studies in our laboratory have reported on the differential distribution
      of several neuropeptides, including the octapeptide cholecystokinin (CCK8), in
      the cerebellar cortex and nuclei of the North American opossum (Didelphis
      marsupialis virginiana). The present account reports on the distribution of CCK8
      binding sites as determined from serial autoradiographic images of the cerebellum
      which were labelled by using [125I]Bolton Hunter sulfated CCK8. Evidence for the
      limited presence of CCK8-like immunoreactivity and CCK8 binding sites in several
      other species suggests that the distribution of this peptide and its receptor(s)
      may be species specific. In the opossum, CCK8-like immunoreactivity is present in
      mossy fiber terminals that distribute throughout the cerebellar cortex; it has a
      very limited distribution in climbing fibers (King and Bishop (1990) J. Comp.
      Neurol. 238, 373-384. CCK8 binding sites are present throughout all lobules of
      the cerebellar cortex and the cerebellar nuclei, which correlates well with the
      distribution of the peptide. CCK8-like immunoreactivity is located primarily in
      the granule cell layer, although the greatest density of binding sites is in the
      molecular layer. The presence of CCK8 is mossy fiber terminals, coupled with the
      presence of CCK8 binding sites in the cerebellar cortex, and the fact that CCK8
      alters the firing rate of Purkinje cells (Madtes et al. (1992) Neurosci. Abstr.
      18, 853) indicate this peptide may function as a neuromodulator in the cerebellum
      of the North American opossum.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7802966
TI  - Contractile units in stress fibers of fetal human astroglia in tissue culture.
AB  - The interaction between myosin and F-actin requires the enzyme, myosin light
      chain kinase (MLCK), as well as Ca(2+)-calmodulin and the calmodulin binding
      protein, caldesmon, which also binds to F-actin. Using immunofluorescence
      staining, we have demonstrated that in human fetal astroglia as in mouse
      astroglia (Abd-El-Basset et al., 1991) the stress fibers contain these
      contractile elements: F-actin, myosin, tropomyosin and caldesmon. F-actin extends
      continuously along the stress fibers, whereas myosin, tropomyosin and caldesmon
      are localized discontinuously in a periodic pattern. In addition, we have
      demonstrated that fetal human astroglia have the enzyme MLCK and calmodulin. The
      association of the contractile elements listed above together with calmodulin and
      MLCK constitutes what may be termed 'contractile units', suggesting that the
      stress fibers in astroglia may be contractile. Contractile stress fibers would
      enable astroglia to exert tension on the matrix surrounding them, thus
      facilitating rapid changes in cell shape.

PMID- 7802967
TI  - Distribution of cocaine recognition sites in rat brain: in vitro and ex vivo
      autoradiography with [125I]RTI-55.
AB  - The distribution of binding sites of [125I]RTI-55 (3 beta-(4-iodophenyl)tropan-2
      beta-carboxylic acid methyl ester), a phenyl tropane analog of cocaine, and the
      selective labeling of the dopamine transporter (DAT) were studied by in vitro and
      ex vivo autoradiography in the rat whole brain. Recent evidence has shown that
      RTI-55 binds to not only DAT but also serotonin transporter (5HTT). In the
      present study, in vitro autoradiography revealed that [125I]RTI-55 bound to the
      olfactory tubercle, the caudate putamen, the accumbens nucleus, the midline and
      lateral geniculate nuclei of the thalamus, the hypothalamic nuclei, the
      substantia nigra compact part, the subthalamic nucleus, the ventral tegmental
      area, the superior colliculus, the dorsal raphe nucleus, and the facial nucleus.
      Further, in the presence of clomipramine, a selective ligand for 5HTT, [125I]RTI
      55 binding was remarkably inhibited in the midline and lateral geniculate nuclei
      of the thalamus, the hypothalamic nuclei, the superior colliculus, the dorsal
      raphe nucleus, and the facial nucleus, while [125I]RTI-55 binding remained in the
      olfactory tubercle, the caudate putamen, the accumbens nucleus, the substantia
      nigra compact part, the subthalamic nucleus, and the ventral tegmental area.
      These findings suggest that [125I]RTI-55 binds to 5HTT in the former areas and to
      DAT in the latter areas. It is therefore concluded that RTI-55 is a suitable
      ligand for studying the action of cocaine in whole brain regions, including the
      thalamus, the hypothalamus and the dorsal raphe nucleus, regions in which cocaine
      is thought to act evoking several neurological effects, e.g., analgesia and
      elevation of adrenocorticotropic hormone. DAT was also labelled selectively both
      in vitro and in vivo using [125I]RTI-55 combined with clomipramine. Therefore,
      radiolabelled RTI-55, combined with unlabelled clomipramine, which displaces its
      binding to 5HTT, also appears to be suitable for the selective imaging of DAT in
      vivo.

PMID- 7802968
TI  - Neuropeptide Y and somatostatin in the neocortex of young and aging rats:
      response to nucleus basalis lesions.
AB  - Lesions of the nucleus basalis of Meynert (NBM) have been used to mimic, in part,
      cholinergic deficits occurring in age-related neurodegenerative disorders, i.e.,
      Alzheimer's disease. In our study, the effect of a persistent cholinergic
      denervation of the fronto-parietal cortex on neuropeptide Y (NPY) and
      somatostatin (SOM) was examined in young adult (3 months old) and aging (> 18
      months old) rats, 1, 3 and 6 months after bilateral stereotaxic NBM lesions with
      quisqualic acid. In aging, non-lesioned rats a significant decrease in
      radioimmunologically and immunohistochemically detectable NPY and SOM was found
      with no further changes after lesions. Morphological markers for these
      peptidergic populations (cell size and number, NADPH-diaphorase histochemistry,
      electron microscopy) demonstrated no signs of alterations in both age groups
      after lesion. Densitometric analysis of peptide fibre networks displayed a
      heterogeneous response with a significant rarefication in young rats 1 month
      after the lesion, followed by restoration and a tendency towards increase 6
      months post lesioning in individual animals. These findings were confirmed by
      radioimmunological measurements. Examination of synaptic and cytoskeletal
      markers, i.e., synaptophysin, GAP-43, MAP-2, Tau-1 and amyloid precursor protein,
      did not reveal any signs for neuronal reorganization or sprouting. These data are
      discussed in the context of plasticity and pathology in age-related
      neurodegenerative disorders with cholinergic impairment.

PMID- 7802970
TI  - The distribution of somatostatin binding sites in the brain of gymnotiform fish,
      Apteronotus leptorhynchus.
AB  - The neuropeptide somatostatin (SS) and its binding sites display a wide
      distribution in the central nervous system of vertebrates. By employing semi
      quantitative autoradiography, we identified such binding sites in the brain of
      the weakly electric fish Apteronotus leptorhynchus (Gymnotiformes, Teleostei).
      Whereas (SS1) binding sites for the octapeptide analogue Tyr3-SMS-201-995 appear
      to be absent in the gymnotiform brain, (SS2) binding sites for the analogue [Tyr0
      D-Trp8]-somatostatin-14 were found in many brain regions and showed a similar
      distribution to that observed by other authors in the amphibian and mammalian
      central nervous system. Telencephalon While binding in the ventral telencephalon
      was typically low, all cell groups of the dorsal portion displayed a high degree
      of binding. The highest density of binding sites was found in the dorsal and
      caudal subdivision 2 of the dorsomedial telencephalon. Diencephalon Many cell
      groups of the diencephalon showed a medium to high degree of binding density. The
      highest level was seen in the habenula. Mesencephalon All layers of the optic
      tectum contained a medium number of binding sites, except the stratum marginale.
      In the torus semicircularis, the different layers displayed distinct binding
      density. While laminae 7-8 showed the highest degree of binding, the lowest
      density was found in lamina 6. Rhombencephalon Binding was generally low or
      absent in the tegmentum. Low levels of binding density were observed in the
      electrosensory lateral line lobe. Cerebellum Extremely high levels of binding
      were found in the eminentia granularis medialis and the eminentia granularis
      posterior. Throughout most regions of the brain, the relative density of binding
      sites and the relative amount of somatostatin immunoreactivity in fibres, as
      determined in previous studies, were in good agreement.

PMID- 7802969
TI  - Sensory and autonomic innervation of the rat eyelid: neuronal origins and peptide
      phenotypes.
AB  - Neuronal origins, peptide phenotypes and target distributions were determined for
      sensory and autonomic nerves projecting to the eyelid. The retrograde tracer,
      Fluoro-Ruby, was injected into the superior tarsal muscle and meibomian gland of
      Sprague-Dawley rats. Labelled neurons were observed within the pterygopalatine
      (31 +/- 6 of a total of 8238 +/- 1610 ganglion neurons), trigeminal (173 +/- 43
      of 62,082 +/- 5869) and superior cervical ganglia (184 +/- 35 of 21,900 +/-
      1741). Immunostaining revealed vasoactive intestinal polypeptide immunoreactivity
      (VIP-ir) in nearly all Fluoro-Ruby-labelled pterygopalatine ganglion neurons (86
      +/- 5%) but only rarely in trigeminal (0.3 +/- 0.3%) or superior cervical (1.4 +/
      1.4%) ganglion neurons. Calcitonin gene-related peptide (CGRP)-ir was not
      observed in pterygopalatine or superior cervical ganglion somata, but was present
      in 24 +/- 4% of trigeminal neurons. Bright dopamine beta-hydroxylase (DBH)
      immunofluorescence was observed in the majority of eyelid-projecting neurons
      within the superior cervical ganglia (65 +/- 5%) and lighter staining was
      detected in pterygopalatine neurons (63 +/- 3%), but no DBH-ir was observed in
      trigeminal neurons. Examination of eyelid sections revealed dense VIP-ir
      innervation of meibomian gland acini and vasculature and modest distribution
      within tarsal muscle. CGRP-ir fibers surrounded ductal and vascular elements of
      the meibomian gland and the perimeter of tarsal muscle. DBH-ir fibers were
      associated with meibomian gland blood vessels and acini, and were more densely
      distributed within tarsal muscle. This study provides evidence for prominent
      meibomian gland innervation by parasympathetic pterygopalatine ganglion VIP-ir
      neurons, with more restricted innervation by sensory trigeminal CGRP-ir and
      sympathetic neurons. Tarsal muscle receives abundant sympathetic innervation, as
      well as moderate parasympathetic and sensory CGRP-ir projections. The eyelid
      contains substantial non-CGRP-ir sensory innervation, the targets of which remain
      undetermined. The distribution of identified autonomic and sensory fibers is
      consistent with the idea that meibomian gland function, as well as that of the
      tarsal muscle, is regulated by peripheral innervation.

PMID- 7802971
TI  - Differential effects of 5,7-dihydroxytryptamine-induced serotoninergic
      degeneration of 5-HT1A receptors and 5-HT uptake sites in the rat brain.
AB  - The time-course of 5,7-dihydroxytryptamine-induced lesions (2, 5 and 14 days
      after i.c.v. injection of 150 micrograms) and the effects of acute reserpine
      treatment (10 mg/kg, i.p., one or 5 days before scheduled death), were evaluated
      by autoradiography of [3H]paroxetine binding sites in the rat brain. Reserpine
      had no significant effect on [3H]paroxetine binding, indicating that the
      depletion of serotonin is not sufficient per se to alter the serotonin uptake
      sites in any region. Two days after the 5,7-dihydroxytryptamine lesion,
      [3H]paroxetine binding was already decreased in the majority of brain regions. In
      the caudate putamen these binding sites were significantly decreased only 14 days
      after the lesion, whereas the ventral tegmental area (or the enclosed median
      forebrain bundle), the dorsal raphe (mainly the ventral portion) and the median
      raphe maintained their high density of serotonin uptake sites even after 14 days.
      Results were similar using [3H]citalopram as ligand for the serotonin uptake
      sites, in the brains of rats lesioned 5 days before death; an exception was the
      ventral portion of the dorsal raphe, where there was a significant increase with
      [3H]paroxetine and a decrease with [3H]citalopram binding. In adjacent sections
      of the same brains we also measured [3H]8-OH-DPAT binding, confirming that it
      completely disappears in the dorsal raphe after the lesion. Thus, considering the
      extent of serotonin cell body degeneration, there appears to be a paradoxical
      mismatch between the excessive loss of [3H]8-OH-DPAT binding and the resistance
      of [3H]citalopram or [3H]paroxetine binding in the dorsal raphe, suggesting that
      the two binding sites may undergo adaptive regulation in surviving neurons.

PMID- 7802972
TI  - External cuneocerebellar projection and Purkinje cell zebrin II bands: a direct
      comparison of parasagittal banding in the mouse cerebellum.
AB  - The parasagittal parcellation of the mammalian cerebellar cortex has been
      revealed using anatomical, electrophysiological, histological and immunological
      techniques. Correlation studies have been carried out to determine whether a
      common organizational plan encompassing the various afferent, efferent and
      intrinsic maps may exist in the mammalian cerebellum. Many of these studies
      utilized the parasagittal Purkinje cell antigenic banding pattern as revealed by
      the monoclonal antibody against zebrin antigens as a standard reference. In this
      study, the pattern of labelled mossy fiber terminals originating from the
      external cuneate nucleus was determined and compared with the Purkinje cell
      antigenic zebrin bands in the same sections. External cuneocerebellar fibers in
      the mouse were observed to project in well-delineated parasagittal terminal
      distribution zones, primarily to the ipsilateral vermal cerebellar cortex.
      However, there was a very minor, but consistent contralateral component. The
      external cuneocerebellar fiber termination pattern in the mouse differed from
      that seen in other rodents such as the rat. Comparison of the external
      cuneucerebellar terminal zones in sections immunohistochemically stained for the
      zebrin II antigen revealed that the boundaries of the terminal fields of the
      external cuneocerebellar projection do not always align with those of the zebrin
      II antigenic bands. These results strongly suggest that mossy fibers have a
      complicated relationship to zebrin defined compartments. Therefore, the
      designation 'functional unit' of the cerebellum or 'cerebellar module' remains
      uncertain at this time.

PMID- 7802973
TI  - Programmed cell death (apoptosis) and cell survival regulation: relevance to AIDS
      and cancer.

PMID- 7802974
TI  - Prostitution and HIV: what do we know and where might research be targeted in the
      future?

PMID- 7802975
TI  - Viral RNA-binding activity of HIV-2 nucleocapsid protein is inhibited by a
      synthetic peptide containing the first zinc finger motif of HIV-2.
AB  - OBJECTIVE: To analyze the antigenic structure and viral RNA-binding activity of
      HIV-2GH-1 nucleocapsid protein (NC). METHODS: Five synthetic peptides
      corresponding to hydrophilic regions of HIV-2GH-1 NC were prepared. The
      reactivity of rabbit antisera directed against these synthetic peptides was
      examined by Western blot (WB) assay, using lysates of purified HIV-2GH-1 virus
      and HIV-2GH-1-infected cells as antigen. The binding activity of NC to viral RNA
      synthesized in vitro, was assessed by Northwestern blot (NWB) assay using 32P
      labeled RNA as a probe. RESULTS: One of five antisera against the peptides
      reacted with a protein of 8 kD (p8) of HIV-2GH-1 in WB. p8 was analyzed for the
      amino-terminal amino-acid sequence and identified as a portion of NC including
      two zinc finger motifs (ZFM), comprising the DNA-binding region in the molecule.
      The binding of the RNA probe to p8 was observed by NWB and did not always depend
      on zinc. In competition experiments, the reactivity of p8 with the RNA probe
      ceased to be evident following preincubation of the probe with a peptide
      containing the first ZFM in the molecule. CONCLUSION: p8 of HIV-2GH-1 NC binds to
      viral RNA in vitro. The first ZFM in the p8 molecule appears to be essential to
      binding activity. Functional analysis of synthetic peptides corresponding to ZFM
      of HIV p8 may provide important information on the development of antiviral
      agents.

PMID- 7802976
TI  - Development of malabsorption and nutritional complications in simian
      immunodeficiency virus-infected rhesus macaques.
AB  - OBJECTIVE: To assess the development and cause of malabsorption in rhesus
      macaques following experimental simian immunodeficiency virus (SIV) infection and
      to evaluate its impact on nutritional status. DESIGN: Clinical malabsorption
      tests and serial jejunal aspirates and biopsies were obtained from nine SIV
      infected and three uninfected animals prior to infection and at 1, 2, 4, 8, 12,
      24, 40 and 52 weeks postinoculation. METHODS: Malabsorption was measured by
      sucrose breath hydrogen (H2) analysis and blood assay of D-xylose. Digestive
      enzyme activity was determined in jejunal mucosal homogenates. Bacterial and
      protozoal flora were determined in jejunal aspirates. Nutritional assessment was
      evaluated using specific blood micronutrient values. Cellular targets of SIV in
      the jejunum were determined by combined in situ hybridization and
      immunohistochemistry. RESULTS: Eight out of nine SIV-infected monkeys, including
      asymptomatic animals, exhibited malabsorption by either increased breath H2
      and/or decreased blood D-xylose. All animals that died of AIDS had diarrhea, D
      xylose malabsorption and decreased sucrase activity. Significant changes in
      nutritional status were associated with malabsorption. Bacterial overgrowth was
      not considered to be a cause of malabsorption. Histopathological biopsy findings
      included dilated villus lacteals, excessive cellular debris, lymphoplasmocytic
      infiltrates and cytoplasmic vacuoles in crypt epithelial cells. SIV-infected T
      cells and macrophages were detected as early as 1 week postinoculation.
      CONCLUSIONS: SIV-associated malabsorption can occur prior to clinical
      complications of disease. Severe intestinal complications are associated with
      malabsorption and malnutrition in the terminal stages of AIDS. The high
      proportion of macaques experiencing malabsorption without detectable pathogens,
      suggests an enteropathogenic role for SIV.

PMID- 7802978
TI  - Detection of subclinical Mycobacterium avium intracellulare complex infection in
      immunodeficient HIV-infected patients treated with zidovudine.
AB  - OBJECTIVE: To test the hypothesis that subclinical Mycobacterium avium
      intracellulare complex (MAC) infection may result in the development of a
      tuberculin response in immunodeficient HIV-infected individuals treated with
      zidovudine. DESIGN: Longitudinal, observational study. SETTING: The Western
      Australian HIV Cohort Study; a prospective, single centre, population-based
      observational study of the natural history of HIV disease. PATIENTS: Forty-nine
      patients with impaired delayed-type hypersensitivity (DTH) responses and negative
      tuberculin responses in whom DTH responses were augmented within 6 months of
      starting zidovudine therapy. OUTCOME MEASURES: Progression to disseminated MAC
      infection stratified according to the presence or absence of a tuberculin
      response in the first 6 months of zidovudine therapy. RESULTS: Twenty-nine of the
      patients developed a post-zidovudine tuberculin response. None of the tuberculin
      non-responders developed disseminated MAC infection during the study period; the
      Kaplan-Meier probability estimate of disseminated MAC infection was 50% at 24
      months and reached 100% 40 months after zidovudine was commenced in tuberculin
      responders. All patients with disseminated MAC infection had become anergic to
      all antigens, including tuberculin, before diagnosis. The probability of a post
      zidovudine tuberculin response was related to the severity of peripheral blood
      CD4+ T-cell depletion, rising from an estimated 20% at 20% CD4+ T cells to 100%
      at < or = 1% CD4+ T cells. CONCLUSIONS: The restoration of a cellular immune
      response against subclinical MAC infection can be demonstrated by measuring the
      DTH response to tuberculin in patients with impaired DTH augmented by zidovudine
      therapy. The findings suggest that MAC infection is almost inevitable, but often
      asymptomatic, in profoundly immunodeficient HIV-infected patients and that a
      prolonged subclinical phase of MAC infection is usual.

PMID- 7802977
TI  - Serological survey of HIV-1, HIV-2 and human T-cell leukemia virus type 1 for
      suspected AIDS cases in Ghana.
AB  - OBJECTIVE: To determine seroprevalence among suspected AIDS patients in Ghana in
      relation to clinical manifestations. MATERIALS AND METHODS: Blood samples and
      medical records were collected from 290 Ghanaian patients with suspected AIDS in
      1990 and 1992. Seroprevalence of HIV-1, HIV-2 and human T-cell leukemia virus
      (HTLV-1) were investigated by the particle agglutination method, indirect
      immunofluorescence assay, the monoepitope enzyme-linked immunosorbent assay and
      Western blot. RESULTS: The specimens were classified into five serologic
      categories: 78 were HIV-1-positive (26.9%), 25 were HIV-2-positive (8.6%), 17
      dual-positive (5.9%), 16 indeterminate (5.5%) and 154 seronegative (53.1%). No
      significant difference was found between the clinical symptoms of patients with
      HIV-1 and HIV-2 infection. Of the patients, 14 (4.8%) were HTLV-1-seropositive,
      of whom 11 were also HIV-positive, indicating a significant correlation between
      the two groups of viral infections (P < 0.01). However, there was no evidence of
      an increase in severity of symptoms in cases of dual infection with HTLV-1 and
      HIV. CONCLUSIONS: HIV-1 infection is now dominant in Ghana in contrast to our
      previous survey in 1986 which showed the dominance of HIV-2. The change in
      seroprevalence suggests that an HIV-1 epidemic has been developing in recent
      years in this country, where HIV-2 was originally endemic. A relatively high
      prevalence of dual-reactive specimens implies the existence of highly cross
      reactive strains of HIV or frequent coinfection with HIV-1 and HIV-2 in the
      region. The large number of seronegative patients with clinically diagnosed AIDS
      raises the question of the inadequacy of AIDS definitions based on clinical
      manifestations only.

PMID- 7802979
TI  - Pulmonary cryptococcosis associated with HIV-1 infection in Rwanda: a
      retrospective study of 37 cases.
AB  - OBJECTIVES: To study the demographic, clinical, radiographic and diagnostic
      features, the clinical course and therapeutic response of pulmonary
      cryptococcosis in HIV-1-infected patients. DESIGN: Retrospective review. SETTING:
      The Department of Medicine of an urban reference hospital in Central Africa.
      METHODS: All the records of HIV-1-infected patients with pulmonary cryptococcosis
      were reviewed retrospectively with regard to the parameters described above.
      RESULTS: Over a 3-year period, pulmonary cryptococcosis was diagnosed in 37 HIV-1
      infected Rwandan patients (21 men, 16 women; mean age, 35 years; range, 26-55
      years). Twenty-nine patients (78%) had primary pulmonary cryptococcosis. Cough
      (94%), weight loss (65%), fever (51%), dyspnoea (46%), thoracic pain (30%),
      headache (13%) and haemoptysis (8%) were the predominant clinical findings. A
      diffuse interstitial infiltrate on chest radiograph was observed in 76% of the
      patients, an alveolar pattern in 19%, mediastinal and/or hilar adenopathy in 11%,
      nodules and pleural effusion each in 5%. Bronchoalveolar lavage, with a yield of
      82%, was found to be the most sensitive diagnostic procedure. Screening of
      cryptococcal antigen in the serum failed to detect cases of primary pulmonary
      cryptococcosis. Twelve patients with primary pulmonary cryptococcosis treated
      with itraconazole as acute and maintenance therapy were all protected against
      disseminated cryptococcal disease; seven out of 10 (70%) of those who did not
      receive a specific anticryptococcal drug developed disseminated cryptococcal
      disease. CONCLUSION: Pulmonary cryptococcosis is not a rare complication of HIV-1
      infection in Rwanda. Its clinical and radiographic patterns are non-specific and
      bronchoalveolar lavage is the procedure of choice for its diagnosis. The natural
      history of untreated primary pulmonary cryptococcosis is disseminated
      cryptococcal disease. Itraconazole is highly effective in the prevention of
      disseminated cryptococcal disease in patients with primary pulmonary
      cryptococcosis.

PMID- 7802980
TI  - Anti-A60 immunoglobulin G in the serodiagnosis of tuberculosis in HIV
      seropositive and seronegative patients.
AB  - OBJECTIVE: A60 is a high molecular weight mycobacterial antigen complex. The
      detection of immunoglobulin (Ig) G antibodies to A60 has been advocated as a
      reasonably sensitive and specific test for active tuberculosis (TB). We aimed to
      compare the sensitivity of this test among HIV-seropositive and HIV-seronegative
      patients with pulmonary TB. METHODS: The presence and concentration of anti-A60
      IgG antibodies was assessed by enzyme-linked immunosorbent assay in 208 HIV
      seropositive and 91 HIV-seronegative Zairian patients with smear-positive
      pulmonary TB. The relationship between anti-A60 IgG levels and HIV serostatus,
      CD4+ lymphocyte counts, presence of clinical AIDS, and tuberculin skin test
      results was verified. RESULTS: Only 36.5% of the HIV-seropositive, compared with
      69.2% of the HIV-seronegative patients had a positive anti-A60 IgG test (P <
      0.00001). Among HIV-seropositive patients, anti-A60 IgG levels did not differ
      according to CD4+ lymphocyte counts, presence of clinical AIDS, or tuberculin
      skin test results. CONCLUSIONS: Among patients with pulmonary TB, the sensitivity
      of testing for anti-A60 IgG was much lower among HIV-seropositive than among HIV
      seronegative patients, even from the early stages of HIV-related
      immunodeficiency. This limits the utility of anti-A60 IgG-antibody testing in the
      diagnosis of TB among HIV-infected patients.

PMID- 7802981
TI  - Response to hepatitis B immunization by infants exposed to HIV.
AB  - OBJECTIVE: To assess the antibody response to hepatitis B immunization in HIV
      infected and uninfected infants. DESIGN: Cohort, comparing hepatitis B surface
      antibody responses of HIV-infected infants with HIV-exposed but uninfected
      infants. SETTING: Urban children's hospital outpatient clinic for families with
      HIV-infected members. INTERVENTION: All infants received hepatitis B vaccine
      according to the American Academy of Pediatrics and Centers for Disease Control
      and Prevention recommended schedule. RESULTS: Forty-one HIV-exposed or infected
      infants were immunized with hepatitis B vaccine in the first year of life. Twenty
      two out of 24 (92%) HIV-exposed but uninfected infants demonstrated an antibody
      response to hepatitis B immunization, compared with six out of 17 (35%) HIV
      infected infants (P < 0.0005). CD4 percentage and CD4 counts were significantly
      lower in the HIV-infected infants than in the uninfected infants, but there was
      no significant difference in CD4 count or percentage between HIV-infected
      responders and nonresponders. CONCLUSION: The humoral immune response to
      hepatitis B immunization, administered before 12 months of age, is significantly
      reduced in HIV-infected children and is independent of CD4 count. Given the large
      number of infants born each year to pregnant women coinfected with HIV and
      hepatitis B, further studies to assess the efficacy of increased doses of antigen
      and variations in the dosage schedule are urgently needed.

PMID- 7802982
TI  - Preparation for phase III HIV vaccine efficacy trials: methods for the
      determination of HIV incidence.
AB  - OBJECTIVE: Accurate estimates of HIV incidence that reflect the effect of non
      vaccine interventions (education, counselling, condom promotion, and possibly
      sexually transmitted disease treatment) and that may be provided in a Phase III
      vaccine efficacy trial, are needed so that vaccine trial population sample sizes
      can be accurately determined. In order to avoid delays in the implementation of
      efficacy trials, well characterized cohorts must also be developed and available
      to participate in such trials. We reviewed the potential study populations, the
      epidemiologic methods for the determination of HIV incidence (using open cohort,
      closed cohort, and seroprevalence data methods), and the need for the development
      of population cohorts in preparation for Phase III HIV vaccine efficacy trials.
      SETTING: Phase III trials in developed and developing countries. METHODS:
      Comparison of open and closed cohorts and those using seroprevalence data to
      estimate HIV incidence. RESULTS: Open and closed cohorts each have disadvantages
      and advantages. However, the open cohort may be more suitable for determining
      estimates of HIV incidence that reflect non-vaccine interventions and for the
      development of a well characterized cohort available to participate in efficacy
      trials. CONCLUSION: Careful preparation of research infrastructures and
      population cohorts will help ensure the successful conduct of scientifically and
      ethically sound HIV vaccine efficacy trials in the future.

PMID- 7802983
TI  - A prospective population-based study of HIV perinatal transmission.
AB  - OBJECTIVE: To estimate the perinatal HIV transmission rate and describe the
      natural history of infant HIV infection in a situation in which HIV status is
      known in more than 95% of delivering women. DESIGN: A cohort of HIV-exposed
      infants born between 7 July 1987 and 30 June 1990, whose mothers were identified
      by routine voluntary universal HIV testing, were followed using clinical and
      laboratory measures. SETTING: Grady Memorial Hospital, a major health-care site
      for individuals of lower socioeconomic status in Atlanta, Georgia, USA, with
      approximately 7000 deliveries per year. PATIENTS: HIV-exposed infants (n = 165),
      98% of whom were African American. RESULTS: Annual maternal HIV seroprevalence
      increased from 0.58 to 0.86%. The annual proportion of HIV-positive women having
      a second delivery increased from 4.3 to 25%. Clinical outcome was known for 132
      out of 165 infants (22 infected and 110 uninfected), the transmission rate was
      17% (confidence interval, 11-24%). The rate declined to 11% by the third year of
      the study. Gestational growth, prematurity and mode of delivery were unrelated to
      infant outcome. There was a trend for intravenous drug use to be more common in
      mothers of infected infants (P = 0.08). After 35 months median follow-up of
      infected infants, eight out of 22 (36%) had an opportunistic infection (seven
      Pneumocystis carinii pneumonia); three out of 22 (14%) had lymphocytic
      interstitial pneumonia, and 10 out of 22 (45%) were asymptomatic or had only
      nonspecific symptoms. Cumulative mortality in infected infants was 9, 32 and 32%
      by 1, 2 and 3 years of age, respectively. CONCLUSION: In this cohort of HIV
      exposed infants, perinatal HIV transmission was 17% overall. Factors affecting
      the transmission rate and possible future changes in the rate require further
      study.

PMID- 7802984
TI  - CD4 lymphocyte count as a determinant of the time from HIV seroconversion to AIDS
      and death from AIDS: evidence from the Italian Seroconversion Study.
AB  - OBJECTIVES: It is well established that a low CD4 lymphocyte count is strongly
      associated with an increased risk of AIDS in HIV infection. We attempted to
      determine whether the link is sufficiently strong that the wide inter-person
      variability in times from HIV infection to AIDS can be explained solely by
      differences in CD4 count experience. METHODS: We followed 1090 HIV-infected
      individuals for up to 12.8 years from seroconversion (median, 3.5 years; 25% for
      more than 5.2 years). The median interval between last negative and first
      positive anti-HIV tests was 9 months. A median of four CD4 counts per subject
      were measured. RESULTS: Individuals with CD4 lymphocyte counts above 250 x
      10(6)/l cells experienced an AIDS incidence rate of one per 339 years (0.3 per
      100 years; 10 cases in 3394 person-years), compared with one per 6 years in those
      whose count had declined below this level (17.2 per 100 years; 96 cases in 559
      person-years) and one per year in those whose count had declined below 50 x
      10(6)/l (100.0 per 100 years; 41 cases in 41 person-years). The AIDS rate
      increased by an average of 33% [relative rate, 1.33; 95% confidence interval
      (CI), 1.20-1.49; P = 0.0001] with every year from seroconversion; one per 46
      years (2.2 per 100 years) for people seropositive for less than 5 years compared
      with one per 14 years (7.3 per 100 years) for those seropositive for more than 5
      years. After adjusting for the tendency for CD4 lymphocyte counts to be higher
      soon after seroconversion, the relative rate declined to 1.07 (95% CI, 0.94-1.22)
      per year from seroconversion (P = 0.32). This result was similar when those
      infected through sharing injecting equipment, homosexual sex, and other routes
      were considered separately. The relative rate per year from seroconversion for
      death due to AIDS fell from 1.41 (P = 0.0001) to 1.00 (P = 0.99) after adjusting
      for CD4 count. CONCLUSIONS: Most of the inter-person variability in time from HIV
      infection to AIDS appears to result from differences in CD4 lymphocyte counts.
      HIV infection appears to cause AIDS and death largely by its ability to induce
      CD4 lymphocytopaenia or some closely correlated abnormality.

PMID- 7802985
TI  - Survival in HIV infection: do sex and category of transmission matter? Swiss HIV
      Cohort Study.
AB  - OBJECTIVE: To examine survival differences in HIV-infected individuals between
      the sexes and the categories of transmission. PATIENTS AND SETTING: Subjects
      assumed to have been infected by injecting drug use, by male homosexual contact
      or by heterosexual contact and enrolled in the Swiss HIV Cohort Study, a national
      multicentre cohort study of adult HIV-infected patients. METHODS: Kaplan-Meier
      lifetable and Cox regression analyses were performed (time 0 = date of study
      entry) and survivors were censored at their last follow-up visit. RESULTS: A
      total of 4428 patients (mean duration of follow-up, 2.1 years) were considered.
      At entry, men were older and had lower CD4+ counts than women (P < 0.0001).
      Homosexual men were the oldest group with the lowest CD4+ counts and the most
      advanced disease at study entry (P < 0.0001). Crude hazard ratios indicated a 28%
      lower mortality from all causes in women compared with men (P < 0.0001) and,
      among men but not in women, a 28 and 32% higher mortality in homosexuals and
      heterosexuals compared with injecting drug users (IDU) (P = 0.0002 and P = 0.008,
      respectively). After adjusting for differences at entry, the mortality difference
      between the sexes disappeared (P = 0.5) and differences across transmission
      categories were reversed. Mortality in homosexual men was an estimated 13% (P =
      0.057) lower than in male IDU; mortality was 22% lower in heterosexual women than
      in female IDU (P = 0.098). In stratified analysis the increased risk in IDU was
      confined to subjects with CD4+ cell counts > 500 x 10(6)/l cells at study entry.
      CONCLUSIONS: These results indicate a uniform mortality risk across the sexes but
      indicate an increased risk in IDU without CD4+ cell depletion at entry, the
      latter probably attributable to causes not related to progression of HIV
      infection. This study underscores the importance of adjusting for prognostic
      factors when comparing survival between different patient groups.

PMID- 7802986
TI  - Knowledge, attitudes and behaviour among HIV-positive and HIV-negative clients of
      a confidential HIV counselling and testing centre in Thailand.
AB  - OBJECTIVE: To describe the clients, operation and impact of an Asian public HIV
      counselling and testing centre. DESIGN AND SETTING: Analysis of samples from
      clients attending the Thai Red Cross Anonymous Clinic (TRC-AC) in Bangkok,
      Thailand in 1993. SUBJECTS: HIV-positive and HIV-negative consecutive clients
      (250 of each). MAIN OUTCOME MEASURES: HIV seroprevalence rates, knowledge,
      attitudes and behaviour. RESULTS: Overall HIV-1 prevalence was 16%; 13% in men
      and 24% in women. Reasons for requesting an HIV test were high-risk behaviour
      (21%), feeling unwell (20%), checking a previous HIV test result (18%), a planned
      marriage or new relationship (10%), and planning a baby (5%). Heterosexual risk
      behaviour was reported by 85% of clients, while in each case only 1% reported
      male homosexual or intravenous drug use risk behaviour. Factors associated with
      HIV infection on univariate analysis included a history of sexually transmitted
      disease, not using condoms, a low level of education and salary, and being
      female. Knowledge about HIV transmission risks and AIDS prevention measures was
      good, and most clients expressed a caring attitude towards people with HIV and
      AIDS. A former negative HIV test result was associated with higher levels of
      condom use, and most clients expressed the intention to reduce their HIV risk
      behaviour in response to a positive or negative HIV test result (more so if
      positive). CONCLUSIONS: Our study demonstrates the demand for and the feasibility
      of confidential HIV counseling and testing services in Thailand and illustrates
      the value of these services in achieving behaviour changes. Such services should
      be considered as an additional approach for reducing HIV transmission in Asia,
      especially in areas with high HIV seroprevalence rates.

PMID- 7802987
TI  - High risk sexual behavior and alcohol consumption among bar-going gay men.
AB  - OBJECTIVES: To determine whether alcohol use prior to sexual behavior influenced
      the occurrence of unprotected anal intercourse among bar-going gay men. METHODS:
      Anonymous AIDS behavioral risk surveys were administered to men entering gay bars
      in 16 cities on three nights in February 1993 in six states in the United States.
      RESULTS: Of the 1519 men who completed the survey, 85% were current alcohol
      drinkers. Men who had unprotected anal intercourse after consuming alcohol drank
      more and reported more incidents of unprotected anal intercourse than men who had
      unprotected anal intercourse but not after drinking. Overall, unprotected anal
      intercourse occurred less frequently after alcohol consumption than without prior
      consumption. CONCLUSIONS: This study found that heavy alcohol use and frequent
      high-risk sexual behavior occurred among the same individuals. However, we found
      no evidence for a causal link between alcohol use and unprotected sexual behavior
      in this sample of bar-going gay men.

PMID- 7802988
TI  - Detection and biologic characterization of infectious HIV-1 in semen of
      seropositive men.
AB  - OBJECTIVE: Factors that influence the infectivity of an individual and the impact
      of antiviral treatment on infectivity are not well defined. This study
      investigated the value of a sensitive method for detecting infectious HIV in
      semen for use as a marker for infectivity. DESIGN: A cross-sectional study of
      infectious HIV in the semen of 33 HIV-positive men. METHODS: A sensitive method
      for detecting infectious HIV in semen was used. The correlation of culture in
      semen with clinical and laboratory data was investigated. Biological phenotypes
      of isolates from blood and semen were tested using an MT-2 assay. RESULTS: HIV
      cultures from seminal cells were positive in 18 patients (55%) and in one patient
      from seminal plasma. Higher recovery rates of HIV from semen correlated with a
      low CD4 count (80% in patients with a CD4 count > 100 x 10(6)/l versus 33% in
      patients with a CD4 count < 100 x 10(6) cells; P < 0.025) and symptomatic disease
      (78 versus 27% in asymptomatic patients; P < 0.01). Recovery of HIV from semen
      was independent of presence or absence of plasma viremia and the biological
      phenotype of blood isolates. Ten patients with syncytium-inducing (SI) isolates
      in their blood had positive semen cultures for HIV. Seven of the 10 patients had
      SI isolates recovered from their semen, whereas three had non-SI isolates only.
      CONCLUSION: Data from partner studies show higher rates of HIV transmission for
      patients with low CD4 counts and symptomatic disease. The compatibility of
      epidemiologic data with our finding that significantly more HIV is recovered in
      semen from patients with advanced disease, suggests that HIV culture of semen
      samples may provide a useful surrogate marker to measure infectivity in clinical
      studies. Further studies are needed to define the inoculum required to transmit
      HIV and to study the impact of sexually transmitted diseases and HIV-1 phenotype
      on semen infectivity.

PMID- 7802989
TI  - Mapping a social network of heterosexuals at high risk for HIV infection.
AB  - OBJECTIVE: To determine how heterosexuals at risk for HIV infection interconnect
      in social networks and how such relationships affect HIV transmission. DESIGN:
      Cross-sectional study with face-to-face interviews to ascertain sociosexual
      connections; serologic testing. PARTICIPANTS: Prostitute women (n = 133), their
      paying (n = 129) and non-paying (n = 47) male partners; injecting drug users (n =
      200) and their sex partners (n = 41). Participants were recruited in sexually
      transmitted disease and methadone clinics, an HIV-testing site, and through
      street outreach in Colorado Springs, Colorado, USA. MAIN OUTCOME MEASURES:
      Reported behaviors, risk perceptions, sociosexual linkages, and HIV prevalence.
      RESULTS: Respondents were well informed, but reported engaging in high-risk
      behaviors frequently. Nevertheless, over 70% of respondents perceived themselves
      to be at low risk for HIV infection. The 595 respondents identified a social
      network of 5162 people to which they belonged. Network analytic methods indicated
      147 separate connected components of this network; eight of the 19 HIV-positive
      individuals in the network were located in smaller components remote from the
      largest connected component. CONCLUSION: The isolated position of HIV-positive
      individuals may serve as a barrier to HIV transmission and may account for the
      lack of diffusion of HIV in heterosexual populations in this region. Network
      analysis appears useful for understanding the dynamics of disease transmission
      and warrants further development as a tool for intervention and control.

PMID- 7802990
TI  - HIV-1 infection among women of reproductive age in a rural district in Malawi.
AB  - OBJECTIVES: To determine HIV-1 seroprevalence in pregnant women attending
      antenatal clinics in a rural district in Malawi, and to estimate the rate of HIV
      1 infection in the district among women of reproductive age. DESIGN AND SETTING:
      Cross-sectional survey conducted from 1987 to 1990 of women enrolled at antenatal
      clinics at four sites (two towns and two villages). METHODS: Questionnaires were
      administered and sera screened at delivery. Population infection estimates were
      based on national census and survey data. RESULTS: Of 3953 pregnant women tested,
      283 (7.2%) were HIV-1-seropositive. Women enrolled at town sites were
      significantly more likely to be HIV-1-infected than village women (11.3 versus
      3.9%; P < 0.001). Higher infection rates were associated with age 20-29 years,
      first or second pregnancy, increased education or socioeconomic status, and
      living within 8 km of the clinic. It was estimated that over 7300 women of
      reproductive age were HIV-1-infected in this rural district. CONCLUSIONS:
      Seroprevalence rates in pregnant women in rural towns were intermediate between
      rates in villages and previously documented rates in cities in Malawi. Although
      village sites had lower seroprevalence rates, they accounted for over half the
      estimated HIV-1 infection in childbearing women in this district.

PMID- 7802991
TI  - HIV testing, HIV infection and associated risk factors among inmates in south
      eastern French prisons.
AB  - OBJECTIVES: To estimate HIV seroprevalence in the two main remand and short-stay
      prisons of south-eastern France and to gather linked anonymous risk-factor
      information. SETTING: Baumettes prison, Marseille, France between 16 November and
      21 December 1992. PARTICIPANTS: Using a self-administered questionnaire about HIV
      testing and risk factors for HIV infection, 295 male and 137 female inmates were
      interviewed. The response rate was 96% (100 and 90% for men and women,
      respectively). At the same time, 279 of a total of 432 (65%) inmates were
      serologically tested for HIV; 153 (35%) declined to provide a blood sample.
      DESIGN: Anonymous cross-sectional and surveillance survey. RESULTS: Twenty per
      cent of participants (84 our of 432) were intravenous drug (heroin) users (IVDU),
      51% of whom reported needle-sharing prior to incarceration; 23% reported more
      than two sexual partners during the last year, and 13% sexual intercourse with an
      IVDU during the last 5 years. HIV status was available for 356 inmates (82%; 65%
      from blood samples and 17% from the questionnaire); 39 were HIV-infected (10.9%;
      95% confidence interval, 7.7-14.2). The inmates not tested for HIV reported
      proportionally less risky behaviours than non-HIV-infected inmates. HIV
      seroprevalence was significantly higher among recidivist inmates (19.9 versus
      4.4%; P < 0.0001). The rate of HIV infection was particularly high among IVDU (34
      out of 84; 40%). More female non-IVDU were HIV-infected than male non-IVDU (4.1
      versus 0.6%; P = 0.04). CONCLUSIONS: This study demonstrates the high prevalence
      of HIV infection in south-eastern French prisons, especially among IVDU. The
      rates may be related to the high prevalence of risky drug practices and to delays
      in the development of HIV prevention programmes for IVDU in France. The higher
      seroprevalence rate among recidivist inmates might be the result of risk
      behaviours during imprisonment. Another hypothesis is that recidivist inmates are
      at greater risk of HIV infection because of higher levels of drug use.

PMID- 7802992
TI  - Inside methodology: HIV surveillance in prisons.

PMID- 7802993
TI  - GalCer, CD26 and HIV infection of intestinal epithelial cells.

PMID- 7802994
TI  - CD26 is not required for infection of the lymphoma cell line C8166 with HIV-1.

PMID- 7802995
TI  - Cell surface expression of CD26 does not correlate with susceptibility to
      immunodeficiency viruses.

PMID- 7802996
TI  - Transient insulin-dependent diabetes mellitus in an HIV-infected patient
      receiving didanosine.

PMID- 7802997
TI  - Peripheral neuropathy associated with cryoglobulinaemia but not related to
      hepatitis C virus in an HIV-infected patient.

PMID- 7802998
TI  - Changes in HIV seroprevalence among blood donors in Benin City, Nigeria.

PMID- 7802999
TI  - Patients' attitudes to zidovudine: the influence of the Concorde trial and the
      media.

PMID- 7803001
TI  - A case of rhombencephalitis with isolation of cytomegalovirus and Mycobacterium
      avium complex in a woman with AIDS.

PMID- 7803000
TI  - Increased p43-isoferritin in Ethiopian immigrants in Israel--a marker for immune
      activation.

PMID- 7803002
TI  - Amalgam retention using pins, boxes, and Amalgambond.
AB  - The purpose of this study was to evaluate and compare the retentive strength of
      amalgam to tooth structure by utilizing pins, boxes, Amalgambond adhesive only,
      and Amalgambond adhesive plus retentive boxes. There was no statistical
      difference (P = 0.05) in retentive strength of the amalgam between the group
      utilizing pins alone and the group utilizing Amalgambond plus retentive boxes.
      However, both of these sample groups demonstrated statistically greater retentive
      strengths than either the boxes only or Amalgambond only groups.

PMID- 7803003
TI  - Caries-like lesion initiation and progression around laser-cured sealants.
AB  - This study evaluated and compared the effects of argon laser and visible light
      polymerization of a pit and fissure sealant material on caries-like lesion
      initiation and progression. Following the lesion initiation period, the primary
      surface lesion depth was significantly less (P < 0.05) for the argon laser-cured
      group (97 microns) when compared with that for the visible light-cured group (151
      microns). Wall lesion occurrence was 5% for both treatment groups. Following
      lesion progression, the primary surface lesion depth was significantly less (P <
      0.05) for the argon laser-cured group (129 microns) when compared with that for
      the visible light-cured group (232 microns). Wall lesion occurrence was 15% and
      5% for visible light-cured and argon laser-cured groups, respectively (P < 0.05).
      Argon laser-curing of sealant material may enhance the caries resistance of the
      enamel forming the enamel-resin interface and result in a reduction in caries
      formation adjacent to sealants.

PMID- 7803004
TI  - Class II glass ionomer cermet tunnel, resin sandwich and amalgam restorations
      over 2 years.
AB  - This study compared the clinical behavior of a glass ionomer (polyalkenoate)
      silver cermet, a posterior resin composite used with the "tunnel" technique, a
      posterior resin composite used with the "closed sandwich" technique, and a high
      copper amalgam for restoring small, proximal surface carious lesions. Two
      dentists placed 86 restorations in the posterior permanent teeth of 26 adults
      treated at a dental hospital. Restorations were assessed at 6-month intervals
      over 2 years for gingivitis adjacent to them, the tightness of proximal contacts,
      occlusal wear, surface voids, roughness and cracking, surface and marginal
      staining, and marginal fracture. Small filling defects, surface voids and
      occlusal wear were obvious with the cermet material, with surface crazing and
      cracking present in 48% of the tunnel restorations. Two of the posterior resin
      composites, but none of the amalgam restorations, also failed. The cermet cannot
      be recommended as a long-term permanent restorative material in situations where
      it is likely to be subjected to heavy occlusal stresses and abrasive wear.

PMID- 7803005
TI  - Occlusal glass ionomer cermet, resin sandwich and amalgam restorations: a 2-year
      clinical study.
AB  - This study compared the clinical behavior of a glass ionomer silver cermet (Ketac
      Silver), a posterior resin composite (Visio-Molar) used with the "sandwich"
      technique, and a high-copper amalgam (Dispersalloy) for restoring conventional
      Class I occlusal cavity preparations. Two dentists placed 116 restorations in the
      posterior permanent teeth of 35 adults treated at a dental hospital. Restorations
      were assessed at 6-month intervals over 2 years for bulk loss of material and
      occlusal wear, surface voids, roughness and cracking, surface and marginal
      staining, and marginal fracture. Losses of material and surface voids were
      obvious with the cermet material, with surface crazing or cracking being present
      in 33% of the restorations. The cermet cannot be recommended as a long-term
      permanent restorative material if the restorations are likely to be subjected to
      heavy occlusal stresses and abrasive wear.

PMID- 7803006
TI  - Sterilization of human teeth: its effect on permeability and bond strength.
AB  - Extracted human teeth were randomly divided into three groups. Group 1 teeth were
      untreated and served as controls. Group 2 teeth were sterilized in a steam
      autoclave. Group 3 teeth were sterilized by exposure to ethylene oxide gas. Crown
      segments were then prepared from these teeth by resection of the roots at the CEJ
      and the occlusal enamel to expose a flat occlusal plane of dentin. The
      permeability of the dentin was determined to be similar in all three groups. The
      shear bond strength of Prisma Universal Bond 3 and C&B Metabond was also similar
      in all groups indicating that sterilization of teeth does not alter dentin
      permeability or bond strength.

PMID- 7803007
TI  - Effect of aging on microleakage of restorative systems.
AB  - This study evaluated the sealing properties of AP.H/Prisma Universal Bond 3,
      Z100/Scotchbond MultiPurpose, AP.H/Imperva Bond, Charisma/Denthesive, Bisfil
      M/All-Bond 2, resin composite/dentin adhesive systems and Fuji II LC light-cured
      glass ionomer, in Class V preparations following 6 months of storage in a 37
      degrees C water bath. The Class V preparations extended just beyond the cemento
      enamel junction of extracted human molars. The restored teeth were placed in 37
      degrees C water for 24 hours and then thermally stressed for 100 temperature
      cycles. Half of the specimens were tested for microleakage at this time. The
      other specimens were returned to water storage and thermally stressed every 30
      days during the following 6 months and then assessed for microleakage by dye
      penetration. AP.H/Imperva Bond, Z100/Scotchbond Multi-Purpose and Fuji II LC were
      not affected by the storage, while AP.H/Prisma Universal Bond 3,
      Charisma/Denthesive and Bisfil M/All-Bond 2 revealed some increase in
      microleakage at the dentin/cememtum margin.

PMID- 7803008
TI  - Bond strength of resin cements to a hybrid composite.
AB  - Tensile bond strengths among three resin inlay cements and a light-cured and a
      post-cured hybrid composite prepared with two different surface treatments and
      three different bond-enhancing liquids were measured in vitro. The resin cements
      were bonded to sandblasted hybrid composite, stored at 37 degrees C in 100%
      humidity overnight, and debonded in tension. Interfacial bond strengths were
      affected most by the type of pre-bond surface treatment. Hydrofluoric acid
      produced weaker bond strengths than surface treatment with phosphoric acid. Post
      cured Herculite XRV produced weaker bond strengths than the light-cured Herculite
      XRV. Porcelite cement produced the highest bond strengths. Of the surface
      enhancers, the acrylic monomer (Special Bond II) produced the highest bond
      strengths, regardless of which cement or surface preparation was used. Fracture
      analysis revealed mostly adhesive failures with hydrofluoric acid treatment in
      both light-cured and post-cured Herculite.

PMID- 7803009
TI  - Localized wear and marginal integrity of posterior resin composites.
AB  - In vitro localized wear testing was completed on several commercially available
      and experimental resin composites to evaluate the loss of occlusal contact wear.
      Marginal deterioration after localized stressing was also evaluated by SEM
      observation. The compositions containing zirconium silicate and quartz exhibited
      the least amount of wear. However, an experimental 4-META bonding resin exhibited
      the best marginal integrity.

PMID- 7803010
TI  - Dentin pretreatment and caries inhibition by a fluoride-releasing resin.
AB  - The purpose of this study was to examine the effect that phosphoric acid etchant,
      used to remove the smear layer, may have on dentin demineralization inhibition.
      Fifteen molars had Class V preparations placed on the mesial and distal surfaces,
      the gingival seat being placed 1 mm below the cementoenamel junction. Randomly,
      one preparation of each tooth had etchant placed carefully on only enamel for 30
      seconds. Etchant was placed on the gingival seat dentin of the remaining
      preparations, as well as the enamel for 30 seconds. A HEMA dentin primer
      containing maleic acid was placed and allowed to dry on the unetched dentin, then
      a Bis-GMA resin with tetrabutyl ammonium tetrafluoroborate was placed. Only the
      fluoridated resin was placed over the dentin that had been etched. All teeth were
      then restored with resin composite and subjected to an artificial caries
      challenge (pH 4.4) for 7 days. Sections 100 microns were obtained, photographed
      under polarized light microscopy and demineralized areas were digitized. Results
      demonstrated the mean area (mm2 +/- S.D.) demineralization 0.5 mm from the
      gingival margin to be: etched dentin (0.77 +/- 0.36); non-etched dentin (1.52 +/-
      0.98). A t-test indicated that there was significantly less demineralization when
      the fluoridated resin came in direct contact with dentin that had the smear layer
      removed (P < 0.05).

PMID- 7803011
TI  - Clinical evaluation of Class V restorations using a total etch technique: 1-year
      results.
AB  - The clinical performance of All Bond 2 and Bis-Fil M used with a total etch
      technique is being monitored in adult patients with erosion/abrasion lesions. 78
      restorations were placed among 36 patients. After a prophylaxis, a short bevel
      was placed on the enamel margin. Using cotton roll isolation, both enamel and
      dentin were conditioned with 10% phosphoric acid for 20 seconds. Both tissues
      were moist at the time of primer application in which several applications of the
      latter resulted in a shiny surface upon gentle air drying. Bonding agent was
      added, brush thinned and polymerized for 20 seconds. The restoration was
      completed with the appropriate shade of composite placed in two increments and
      finished with fine grit diamonds and polishing paste. Evaluation criteria
      according to Ryge included retention, color match, visual and tactile margin
      integrity, secondary caries and postoperative sensitivity. A 1-year recall of 73
      restorations showed 98.6% retention with 95.8% Alfa color match and stain-free
      margins. Tactile integrity was 83.1% Alfa. There was no secondary caries nor
      postoperative sensitivity. It was concluded that these preliminary findings offer
      cautious optimism for this system and the total etch procedure.

PMID- 7803012
TI  - What does it mean to be a professional?

PMID- 7803013
TI  - Depression in children after tonsillectomy.
AB  - Postoperative depression has been reported in adults undergoing open heart
      surgery and mastectomy. Tonsillectomy is a commonly performed procedure and can
      be associated with significant morbidity including pain, difficulty swallowing,
      dehydration, and bleeding. While adults may be able to express their feelings
      about the postoperative course, children often are unable to express themselves.
      Because postoperative depression may manifest itself in unusual behavior that is
      dismissed as "expected," it may go unrecognized. We present three case reports in
      which the child demonstrated signs of depression following tonsillectomy. We
      believe that depression following tonsillectomy occurs more frequently than has
      been recognized. We describe the diagnosis and management of posttonsillectomy
      depression to increase the otolaryngologist's awareness of this entity.

PMID- 7803014
TI  - Laryngeal tuberculosis. A cause of stridor in children.
AB  - The number of tuberculosis (TB) cases reported in the United States has been on
      the decline for the last three decades. This trend has been dramatically reversed
      in the past few years, largely owing to the human immunodeficiency virus
      epidemic. Laryngeal TB, while well recognized in the adult population, is a rare
      disease in children. Only six cases have been described in the world literature
      since 1960. We describe three children with laryngeal TB who presented with
      stridor. One child required an emergency tracheotomy for control of the airway.
      The pathogenesis of laryngeal TB in children is postulated to differ from that in
      adults. In children primary infection of the larynx occurs, while in adults,
      laryngeal infection is secondary to pulmonary disease. All patients had triple
      anti-TB chemotherapy for 1 year. Laryngeal TB, although rare, may be seen more
      frequently in the near future and the diagnosis should always be considered.

PMID- 7803015
TI  - Parathyroid adenoma associated with a branchial cleft cyst.
AB  - An unusual case of parathyroid adenoma is presented. This adenoma presented as a
      rapidly expanding neck mass in a normocalcemic patient. It was located far
      laterally in the neck, in association with the internal jugular vein and with a
      branchial cleft cyst. This case provides an unusual presentation of parathyroid
      adenoma. It also provides an elegant demonstration of developmental anatomy as
      well as the mechanism of parathyroid ectopia in the lateral aspect of the neck.

PMID- 7803016
TI  - Vocal cord injection in children with unilateral vocal cord paralysis.
AB  - Unilateral vocal cord paralysis (UVCP) in children is uncommon and rarely leads
      to serious sequelae. However, on rare occasions, it can present with severe
      aspiration and dysphonia. Several therapeutic techniques have been used in adults
      with UVCP, but the reported alternatives in children have been much more limited.
      Observation and speech therapy are the standard treatment. We describe three
      children with UVCP and severe aspiration who were treated with vocal cord
      injection. The treatment indications, clinical courses, and outcomes of the three
      cases are detailed. The injection of vocal cords in children is discussed, with
      an emphasis on those aspects unique to the management of UVCP in pediatric
      patients. Alternative surgical treatment modalities are also presented. Vocal
      cord injection is an effective and viable therapeutic option for the management
      of UVCP in certain pediatric patients with severe aspiration and dysphonia.

PMID- 7803017
TI  - Congenital cholesteatoma.
AB  - OBJECTIVE: To review the characteristics of congenital cholesteatomata. DESIGN:
      Case series. SETTING: Tertiary care (referral-based) private practice. PATIENTS
      AND OTHER PARTICIPANTS: Fourteen patients were included in the study. The
      diagnosis of congenital cholesteatoma was based on an intact tympanic membrane on
      physical examination; a history that excluded tympanic membrane perforation,
      otorrhea, or previous otologic procedure; and a documented cholesteatoma at the
      time of surgical removal. INTERVENTION: Surgical procedures including
      tympanotomy, atticotomy, and tympanotomy with mastoidectomy were performed on all
      patients. MAIN OUTCOME MEASURES: Removal of cholesteatoma. RESULTS: Four of the
      14 patients had lesions isolated to the anterosuperior quadrant of the tympanum;
      the remainder had more extensive disease with notable posterior tympanic
      involvement. Three of the patients underwent surgery for recidivism; none were
      from isolated anterior lesions. One of these patients was referred at the time of
      recurrence, one had known residual cholesteatoma, and one had recurrence.
      CONCLUSIONS: Clinical presentation and surgical findings enable the
      differentiation of two separate sites of congenital cholesteatoma formation: the
      anterosuperior and posterior-superior regions of the tympanic cavity. Recidivism
      of the lesion appears more commonly with posterior-superior congenital
      cholesteatomas.

PMID- 7803018
TI  - Enlarged vestibular aqueduct and sensorineural hearing loss in childhood.
AB  - OBJECTIVE: To determine if all children with enlarged vestibular aqueducts (EVAs)
      have development of uniform progressive sensorineural hearing loss (SNHL). To
      determine whether the size of the EVA correlates with severity, frequencies
      involved, and stability of SNHL. To determine if the audiologic pattern of SNHL
      correlates with likelihood of progression of SNHL. DESIGN: Retrospective study.
      SETTING: Children's National Medical Center, Washington, DC, a tertiary care
      center with a large otologic practice. PATIENTS: Fifteen children (26 ears) with
      EVA on computed tomographic scan. METHODS: History, physical examination,
      computed tomographic scans, and serial audiograms were reviewed. Factors analyzed
      included age at diagnosis, audiometric configuration (high tone, midtone, low
      tone, flat), degree of hearing loss at presentation, length of follow-up, and
      presence of associated inner ear anomalies. RESULTS: Nine ears had progressive
      SNHL, 16 ears had stable SNHL, and 1 ear had profound SNHL. The predominant
      audiologic configuration was flat. The audiogram configuration does not correlate
      with progression of SNHL. The size of the vestibular aqueduct does not correlate
      with the level, type, or progression of SNHL. CONCLUSION: Our study failed to
      uncover factors that might be predictive of progression of hearing loss. We
      conclude that until a better understanding of the natural history and
      pathophysiologic condition of EVAs is achieved, there is no surgical or other
      intervention that can be demonstrated as being efficacious.

PMID- 7803019
TI  - Disability in Meniere's disease.
AB  - OBJECTIVE: The purpose of this study was to determine the level of disability
      among patients with Meniere's disease, information needed by clinicians when
      evaluating patients for coverage under the Americans With Disabilities Act. We
      hypothesized that the unpredictability of vertiginous episodes or "Meniere's
      attacks" would be the most disabling problem, combined with the lack of a safe
      place to sit down during Meniere's attacks. DESIGN: All patients seen in the
      otolaryngology faculty practice at Baylor College of Medicine, Houston, Tex, and
      diagnosed as having Meniere's disease over a 3-year period were sent a self
      administered questionnaire. SETTING: This practice is located at a tertiary care
      center. SUBJECTS: One hundred forty-nine potential subjects constituted the pool,
      from which data from 50 subjects provided complete data sets. RESULTS: The data
      from 50 adults suggested that the most problematic symptom was vertigo, followed
      by hearing loss. The unpredictability of Meniere's attacks and the lack of a safe
      place to rest during attacks was a significant problem for few subjects.

PMID- 7803020
TI  - Peripheral generators of the vestibular evoked potentials in the cat.
AB  - OBJECTIVES: The contributions of each of the vertical semicircular canals (SCCs)
      and otoliths to the short-latency vestibular evoked potentials in response to
      angular acceleration impulses were studied in the cat. DESIGN: The experiments
      were conducted on unilateral labyrinthectomized cats. Vestibular activation was
      achieved by delivering angular acceleration impulses to the animal's head, held
      in the position presumed to be optimal for maximal stimulation of either the
      anterior or the posterior SCCs before and after obliteration of the SCC studied,
      and before and after obliteration of the other SCCs and ablation of the maculae.
      INTERVENTIONS: Unilateral labyrinthectomy, obliteration of the SCCs, and ablation
      of the otoliths and section of the commissural vestibular fibers in the brain
      stem with histologic confirmation were carried out in the experiments. RESULTS:
      Following selective obliteration of either the anterior or the posterior SCC of
      the remaining ear and stimulation in the presumed optimal plane of the
      obliterated canal, the early prominent waves (P1 and P2) disappeared, leaving
      only much smaller-amplitude waves. These were severely depressed after ablation
      of the maculae. On the other hand, the vestibular evoked potentials in response
      to excitatory stimuli were not affected by obliteration of the other two SCCs and
      ablation of the maculae. CONCLUSION: These results indicate that when the head is
      stimulated in the optimal plane of each of the SCCs, the vestibular evoked
      potentials are generated mainly by the cristae ampullaris being stimulated, while
      the otoliths contribute smaller responses.

PMID- 7803021
TI  - Ototoxicity of topical ticarcillin and clavulanic acid in the chinchilla.
AB  - BACKGROUND: Currently available topical otic preparations contain a variety of
      antibiotics and other ingredients that are potentially damaging to the middle and
      inner ear. There is therefore a need to identify agents that are safe as well as
      effective for topical otologic use. In pursuit of that goal, we used an animal
      model to evaluate the ototoxic potential of the broad-spectrum, penicillin
      derivative ticarcillin--both alone and combined with clavulanic acid (a beta
      lactamase inhibitor). METHODS: Twenty chinchillas served as subjects. Ten of the
      animals were given a single middle ear application of ticarcillin; the remaining
      10 animals received ticarcillin disodium plus clavulanate potassium (Timentin).
      Five animals from each of the two groups were killed after 1 week to assess short
      term effects and the other five animals in each group were kept for 4 weeks
      before their temporal bones were removed for histologic study. RESULTS:
      Significant toxic effects, involving both the middle and inner ear, were observed
      in all experimental groups. Alterations of the middle ear at 1 week included
      inflammation, hemorrhage, and effusions. Middle ear cholesteatomas were observed
      at 4 weeks. Inner ear changes seen at 1 and 4 weeks included hair cell loss,
      supporting cell degeneration, and strial damage. CONCLUSION: The study results
      indicate that ticarcillin should not be considered for further evaluation as a
      possible antibiotic for use in ototopical preparations.

PMID- 7803022
TI  - Tympanic electrocochleography for diagnosis of Meniere's disease.
AB  - OBJECTIVE: Tympanic electrocochleography (ECOG) is a noninvasive technique for
      recording cochlear potentials with an electrode placed on the tympanic membrane.
      Electrocochleography is used clinically in the evaluation of patients for
      endolymphatic hydrops. This study was undertaken to obtain normative data for
      ECOG responses to clicks and tone bursts and to determine clinical indicators
      that result in high test specificities. DESIGN: Three cochlear potentials were
      measured; the eighth nerve compound action potential, the cochlear microphonic,
      and the summating potential. The subjects were 53 normal hearing adults with
      negative histories for symptoms of Meniere's disease. The ECOG responses were
      measured with a silver wire-rayon wick electrode that was placed on the tympanic
      membrane under direct microscopic visualization. Stimuli were condensation,
      rarefaction, and alternating polarity clicks and 1- and 2-kHz tone bursts.
      RESULTS: Measures that appear to be useful in the evaluation of endolymphatic
      hydrops include the summating potential to action potential ratio, action
      potential latency difference to condensation and rarefaction clicks, and the tone
      burst-evoked summating potential. Relationships among these measures were
      investigated, and abnormal criteria were determined that result in test
      specificities of 95%. CONCLUSIONS: Meniere's disease is viewed as a progressive
      disease in which ECOG characteristics vary with the disease state. Cases are
      presented to illustrate ECOG responses in various stages of the disease. The
      normative data presented in this article are useful for the detection of
      Meniere's disease in its early stages.

PMID- 7803023
TI  - Microtia and significant auricular malformation. Ninety-two pediatric patients.
AB  - OBJECTIVE: To study congenital auricular malformation, an uncommon but serious
      condition. The literature about auricular malformation separates the medical,
      otologic, and auricular reconstructive elements; this study addresses all
      elements in a single report. DESIGN: A retrospective chart analysis of patients
      with microtia and severe auricular malformation from initial presentation through
      surgical reconstruction for those of appropriate age. SETTING: A single author's
      experience in a practice at a referral institution. PATIENTS: Ninety-two patients
      (108 ears). RESULTS: Early presentation at less than 1 year of age was noted for
      40 patients. Coexisting medical conditions were noted in 16 patients. Seven
      patients demonstrated facial paralysis. Unexpected sensorineural hearing loss was
      discovered in six patients. Twenty-four patients had undergone auricular
      reconstruction at the time of this report. Additional patients had undergone skin
      tag removal, ventilation tube placement, and atresia repair. CONCLUSIONS:
      Children with microtia and significant auricular malformation require global
      attention to early family guidance, to expected and unexpected hearing loss, to
      language development, to associated medical conditions, and to both auricular and
      otologic reconstruction issues.

PMID- 7803024
TI  - Therapeutic embolization in the treatment of intractable epistaxis.
AB  - OBJECTIVE: To determine the effectiveness of therapeutic embolization in the
      treatment of intractable epistaxis. DESIGN: Cohort. SETTING: Tertiary care
      hospital. PATIENTS: Consecutive referred sample of 57 patients with intractable
      epistaxis. INTERVENTION: Percutaneous transfemoral catheterization and
      angiography of the internal maxillary arteries. Embolization of the most distal
      branches with 0.1- to 0.9- cm3 medium-sized polyvinyl alcohol particles on the
      suspected side of bleeding. OUTCOME: Outcome was successful if no further
      interventional treatment was required for epistaxis. RESULTS: Anatomical
      abnormalities precluded embolization in three patients. Three of the remaining 54
      patients required supplementry embolization. Including these three patients, 52
      (96%) of 54 patients had successful control epistaxis. The major neurologic
      complication rate was 6% (three of 54 patients), with no permanent deficits.
      CONCLUSIONS: Therapeutic embolization is an effective and safe technique and
      should be considered as the primary treatment modality in severe epistaxis.

PMID- 7803025
TI  - Rigid fixation of vascularized bone grafts in mandibular reconstruction.
AB  - OBJECTIVE: To evaluate the nature of complications and complication rates with
      the use of three different reconstruction plates for the rigid fixation of
      vascularized bone grafts in oromandibular reconstruction. DESIGN: We conducted a
      case series of 95 patients over a 6-year period, with a minimum follow-up of 6
      months and a maximum follow-up of 66 months. SETTING: Academic tertiary referral
      medical center. PATIENTS: Forty-eight patients had vascularized bone grafts
      fixated to native mandible with AO stainless steel reconstruction plates; 25
      patients, with AO titanium plates; and 22 patients, with titanium hollow screw
      reconstruction plates (THORPs). Types of vascularized flaps, mandibular defects
      to be reconstructed, and use of radiation therapy were similar among the three
      groups. INTERVENTION: The surgical approach involved oromandibular reconstruction
      with a vascularized bone graft rigidly fixated with a reconstruction plate.
      OUTCOME MEASURES: Clinically and radiographically noted complications and
      resultant treatment. RESULTS: In the grafts fixated with AO stainless steel
      reconstruction plates, three plate fractures, seven instances of loose screws,
      eight plate exposures, and two cases of nonunion occurred. No cases of plate
      fracture or nonunion occurred in the titanium or THORP groups. One titanium plate
      and two THORPs were exposed during the study period. One instance of loose screws
      occurred in the titanium group; none in the THORP group. Seventy-four percent of
      those complications occurred within 12.4 months (the mean follow-up time of the
      THORP group). The incidence of complications in the stainless steel group was
      significantly greater than that in the titanium or THORP groups. No statistically
      significant increase in the rate of complications was noted when radiation
      therapy was used as a component of treatment. CONCLUSIONS: To our knowledge, this
      is the first study to compare three different reconstruction plates for fixation
      in vascularized bone reconstruction of the mandible. AO THORPs are now used
      almost exclusively to rigidly fixate vascularized bone grafts because of their
      advanced design and their potential for osseointegration and because fewer screws
      are necessary to attain adequate fixation than with conventional AO
      reconstruction plates.

PMID- 7803026
TI  - Comprehensive management of the eye in facial paralysis.
AB  - OBJECTIVE: To determine guidelines for the management of paralyzed eyelids
      following facial palsy, including surgical indications, timing, and type of
      procedure(s). DESIGN: Prospective analysis of 60 patients diagnosed as having
      complete facial palsy. Follow-up ranged from 18 to 36 months. PATIENTS: All
      subjects had a complete unilateral facial palsy of various origins. Ages ranged
      from 6 to 81 years. INTERVENTIONS: Forty patients underwent evoked
      electromyography and blink reflex testing of the facial nerve. Twenty additional
      patients had a known fifth-degree nerve injury that did not require testing. MAIN
      OUTCOME MEASURE: Lack of interval improvement in clinical results of examination
      and/or evoked electromyography, coupled with length of time from injury, were
      used to determine surgical candidacy. All patients with fifth-degree nerve injury
      were considered surgical candidates, with clinical examination results of eyelid
      function used to determine which procedure(s) to be performed. RESULTS: Of the 60
      patients evaluated with facial palsy, 43 patients required surgical restoration
      of eyelid function. Forty-one patients required gold weight implants; 18 of these
      also required shortening of the lower eyelid. Two additional patients underwent
      eyelid shortening without gold weight implantation. Seventeen patients were
      treated only with corneal lubricants and moisturizers. No gold weights extruded;
      there were no infections. Two patients required revision of their lower eyelid
      surgery owing to progressive laxity. Four patients have had their gold weights
      removed an average of 9.5 months following insertion. CONCLUSIONS: The degree of
      neural injury and its associated regeneration time, determined clinically and by
      evoked electromyography, are useful factors to assist in patient selection,
      surgical timing, and type of procedure(s) necessary to fully rehabilitate the
      upper and lower eyelids following facial paralysis.

PMID- 7803027
TI  - Long-term effect of uvulopalatopharyngoplasty on driving performance.
AB  - OBJECTIVE: It has been questioned whether the effect of uvulopalatopharyngoplasty
      lasts as years go by. From a previous study it is known that patients with severe
      rhonchopathy, complaining of sleepiness at the wheel, improve their vigilance and
      driving performance immediately following uvulopalatopharyngoplasty, but is this
      effect persisting? DESIGN: In a cohort study, the long-term effect of surgical
      treatment on driving vigilance was evaluated on 13 middle-aged (median, 52 years)
      male patients and five matched controls. Three to 4 years postoperatively, they
      were subjected to a boring 90-minute-long retest in an advanced driving simulator
      and daytime polysomnography, identical to those performed preoperatively. Factors
      measured were brake reaction time, lateral position deviation, and off-road
      incidents. The patients were also asked to assess their driving skills on a self
      report and their vigilance on a visual analogue scale. RESULTS: All but one
      patient reported themselves as being more vigilant and safe drivers following
      surgery. Objective results showed that the initial improvement in brake reaction
      time, lateral position deviation, and number of off-road incidents was sustained,
      but not always in concordance with the apnea index. CONCLUSION: The positive
      effect of uvulopalatopharyngoplasty on vigilance and driving performance remains
      after 4 years. This may have a substantial impact on traffic safety.

PMID- 7803028
TI  - Autologous free dermal fat graft. Reconstruction of facial contour defects.
AB  - OBJECTIVE: To examine the use of autologous free dermal fat grafts (FDFGs) in the
      reconstruction of soft-tissue facial contour defects, an 8-year, retrospective,
      computerized medical chart review was conducted for 21 patients who underwent
      reconstruction with FDFGs. SETTING: Section of Facial Plastic and Reconstructive
      Surgery, Department of Otolaryngology, Oregon Health Sciences University,
      Portland, or affiliated hospitals. PATIENTS: Twenty-one patients identified in
      the chart review were included in the retrospective evaluation. Follow-up periods
      ranged from 11 to 94 months. Five patients were unavailable for follow-up at the
      chart review, but all five had satisfactory results at their last evaluation.
      DESIGN: Soft-tissue augmentation was performed using autologous FDFGs harvested
      from the abdomen following in situ de-epithelialization with a high-speed
      dermabrader. Facial contour defects resulted from tumor extirpation, congenital
      deformity, trauma, or degenerative disease. MAIN OUTCOME MEASURES: Outcome was
      considered satisfactory when the patient and the surgeon were pleased with the
      long-term results at the last evaluation. RESULTS: Complications, including graft
      resorption (five patients) and epithelial cyst formation (two patients), were
      observed in seven patients and resulted in an unsatisfactory outcome. The
      remaining 14 patients demonstrated satisfactory results as determined by the
      patient and the surgeon at the last evaluation. CONCLUSIONS: Successful long-term
      augmentation of facial contour defects may be achieved with autologous FDFGs in
      an appropriate patient population. Careful patient selection and proper surgical
      technique are essential for satisfactory long-term results. Guidelines are
      provided for the augmentation of facial contour defects with autologous FDFGs.

PMID- 7803029
TI  - [Carlo Giacomini and brain histology].

PMID- 7803030
TI  - Toward a functional analysis of drug treatment for behavior problems of people
      with developmental disabilities.
AB  - A brief review of the use of psychotropic medications for people with
      developmental disabilities was presented. Although in some cases therapeutic
      effects were obtained, in many cases no positive effects, or negative ones, were
      observed. We suggest that prescribing drugs based on topographical features of
      the problem behavior (e.g., self-hitting), without considering the function the
      behavior serves for an individual, contributes to the variability in clinical
      response. Functional analyses of behavior disorders, with appropriate
      consideration of the neurochemical and developmental variables involved, may
      provide the basis for a more rational approach to pharmacotherapy for people with
      developmental disabilities.

PMID- 7803031
TI  - Social preferences by and for pigtailed macaques (Macaca nemestrina) with trisomy
      18.
AB  - Social choices of trisomic macaques (macaca nemestrina) were compared with those
      of age-matched controls and of infants and adult females without handicaps. All
      groups chose social over nonsocial stimuli and showed few differences in their
      preferences for stimulus animals with and without handicaps. On initial
      encounter, the trisomic monkeys were socially interesting to age-matched controls
      and to younger animals and adult females. Thus, avoidance of individuals with
      handicaps probably is not a general primate trait. Even though the trisomic
      monkeys showed inappropriate social and motor behavior in play groups, their
      preference for social stimuli demonstrates that the presence of mental
      retardation and physical handicaps need not reduce positive social motivation
      even when prior social experiences have been largely negative.

PMID- 7803032
TI  - Age, adaptive behavior, and Alzheimer disease in Down syndrome: cross-sectional
      and longitudinal analyses.
AB  - Cross-sectional and longitudinal analyses were used to compare age-related
      changes in adaptive functioning in institutionalized adults with and without Down
      syndrome. Cross-sectional analysis showed significant differences related to
      level of functioning but not to age or etiology of disability. Longitudinal
      analysis showed a pattern of decline in self-help and communication skills in
      several individuals with Down syndrome older than 40. The case of an adult with
      Down syndrome with confirmed Alzheimer pathology at postmortem was presented.
      Results were discussed in relation to aging and the likelihood of Alzheimer-like
      changes in individuals with Down syndrome.

PMID- 7803033
TI  - Strength deficit of knee extensor muscles of individuals with Down syndrome from
      childhood to adolescence.
AB  - The isokinetic strength of the knee extensor muscles of both limbs, at the speed
      of 30 degrees/second, was evaluated in 25 children and adolescents with Down
      syndrome. Comparison with two control groups of 40 intellectually average
      individuals and 30 individuals with mental retardation of unknown origin showed
      that both children and adolescents with Down syndrome were weaker than were the
      control subjects. Moreover, by the age of 14 years, adolescents with Down
      syndrome failed to show the muscle strength increase that physiologically occurs
      by this age. Interlimb comparison of knee extensor muscles showed a strength
      dominance in the 44% of individuals with Down syndrome, with a prevalence for the
      left leg. In conclusion, our data suggest the presence of a dysfunction of the
      neuromuscular system both at the level of the pyramidal system and/or of the
      neuromuscular junction, possibly as an expression of premature ageing.

PMID- 7803034
TI  - Explanatory model to describe school district prevalence rates for mental
      retardation and learning disabilities.
AB  - Data reports from South Carolina's 92 independent school districts were used to
      calculate prevalence rates of mental retardation and learning disabilities among
      school-age children. These prevalence rates were 41.66/1,000 children enrolled
      for mental retardation and 33.21/1,000 children enrolled for learning
      disabilities. The 1980-1981 school year was selected because this was the last
      year in which disaggregated reports were submitted for placement in educable
      mental handicap (EMH), trainable mental handicap (TMH), and profound mental
      handicap (PMH) programs. Exploratory factor analysis and multiple regression
      analysis were used to explain school district prevalence rates of categorization
      of children into programs for mental retardation and learning disabilities.
      Results show that community SES and tax inputs explain 39% of the variation in
      prevalence rates and that these factors affect rates indirectly.

PMID- 7803035
TI  - The "intelligence" of calendrical calculators.
AB  - Strategies of 4 men (WAIS-R range 65 to 76) when making calendar calculations
      were investigated. Each subject completed a battery of standardized psychological
      tests. Results suggested that subjects were aware of rules and regularities
      associated with the calendar, including knowledge of the 14 different calendar
      templates, one of which describes any calendar year. Their strategies were
      rigidly applied and could not be modified easily, even when doing so would have
      facilitated performance. The involvement of practice, memory, anchor dates,
      eidetic imagery, and mathematical algorithms were discussed. We concluded that
      these savants relied heavily on memory, with little manipulation of cognitive
      input, as opposed to transforming stimuli.

PMID- 7803037
TI  - Suppression of irrelevant location information by individuals with and without
      mental retardation.
AB  - Negative priming in a location task was examined for individuals with and without
      mental retardation. In each prime display, a target stimulus was presented in one
      of four locations, with a distractor stimulus appearing in another location. The
      target in the probe appeared either in the same position as the target in the
      prime, the same position as the distractor, or a different position from both. In
      contrast to results obtained using identification tasks (Cha & Merrill, 1994),
      all subjects exhibited interference to locating the target in the negative
      priming condition. All individuals apparently actively suppressed response
      tendencies to the location of irrelevant information in the prime display.

PMID- 7803036
TI  - Validity of the Reiss Screen for Maladaptive Behavior.
AB  - The validity of the subscales of the Reiss Screen for Maladaptive Behavior in an
      institutional population was examined by correlating these scores with the
      Psychopathology Instrument for Mentally Retarded Adults (PIMRA), the Aberrant
      Behavior Checklist, and programmatic measures, such as psychiatric diagnoses,
      psychotropic medication, behavior therapy programs, and presence on a dual
      diagnosis unit. Results of this study broadly replicated the previous research on
      the validity of the Reiss total score. Evidence for the validity of the subscales
      was more limited, possibly due to limitations in the internal consistency of the
      Reiss or PIMRA subscales.

PMID- 7803038
TI  - Magnetic resonance imaging of the paranasal sinuses and nasal cavities.
AB  - Magnetic resonance imaging has proven to be a useful tool for imaging the
      paranasal sinuses and nasal cavities. Of particular interest in this region is
      the ability to distinguish between lesions that are highly cellular with little
      free water (neoplasms) and lesions that have significant amounts of serous and
      mucinous secretions and thus contain predominantly free water (infections).

PMID- 7803039
TI  - Magnetic resonance imaging of the pharynx and larynx.
AB  - Imaging of the pharynx and larynx has been a difficult challenge for many years.
      The advent of magnetic resonance imaging (MRI) with its superior soft tissue
      contrast resolution and multiplanar capabilities has allowed the imaging
      specialist to examine these structures with unparalleled precision. The recent
      developments in MRI can also aid the oncologist, surgeon, and radiation therapist
      in developing a more comprehensive treatment plan for patients with pharyngeal
      and laryngeal neoplasms. This article describes the important advances in MRI of
      the pharynx and larynx.

PMID- 7803040
TI  - Magnetic resonance imaging of the oral cavity and tongue.
AB  - The oral cavity is the oral portion of the upper aerodigestive tract separated
      from the oropharynx by the soft palate, anterior tonsillar pillars, and
      circumvallate papillae. The anatomy of the components of the oral cavity,
      including the oral tongue, the floor of the mouth, the retromolar trigone, the
      hard and soft palates, the buccal mucosa, and the gingiva, are described. The
      pathology discussion includes both malignant (predominantly squamous cell
      carcinomas) and benign disease entities commonly detected in this region.

PMID- 7803041
TI  - Magnetic resonance imaging of soft tissues of the neck.
AB  - Magnetic resonance imaging (MRI) has proven to be an ideal examination for
      evaluating a variety of soft tissue lesions in the extracranial head and neck. In
      this article we will describe the MRI characteristics of a variety of the soft
      tissue lesions found in the neck. Pathophysiology, clinical presentation,
      treatment, and prognosis are also discussed.

PMID- 7803042
TI  - Treatment with IGF-I peptides improves function of the remnant gut following
      small bowel resection in rats.
AB  - The effects of 7 days' s.c. infusion of 111-700 micrograms/day IGF-I on gut
      growth and absorptive function were examined in growing rats following removal of
      70 or 80% of the jejuno-ileum, and compared with the responses to the analogues,
      LR3IGF-I and des(1-3)IGF-I, which bind poorly to IGF binding proteins.
      Administration of 278 micrograms/day IGF-I, LR3IGF-I or des(1-3)IGF-I following
      70% jejuno-ileal resection significantly attenuated malabsorption of fat and
      nitrogen. Responses in rats with 80% resection were less substantial, but a dose
      responsive reduction in malabsorption was apparent with LR3IGF-I. Both IGF-I and
      LR3IGF-I were shown to increase body weight gain and food conversion efficiency
      in a dose-dependent manner following 80% jejuno-ileal resection. Total gut weight
      was increased by up to 21%, due predominantly to increased weight of the stomach
      and proximal small bowel, with the latter effect attributable at least in part to
      an increased bowel length. LR3IGF-I was more potent than IGF-I at stimulating
      body weight gain and food conversion efficiency, but its potency advantage on gut
      absorptive function and small intestinal re-growth was less marked. We conclude
      that administration of IGF-I peptides improves gastro-intestinal absorptive
      function following partial gut resection, most likely reflecting, at least in
      part, an increase in gut absorptive surface area.

PMID- 7803043
TI  - Expression of basic fibroblast growth factor (FGF-2) messenger ribonucleic acid
      is regulated by testosterone in the rat anterior pituitary.
AB  - Evidence from in vivo studies supports the concept that growth factors are
      involved in the function of endocrine organs. We studied the effects of target
      endocrine organs (thyroid, adrenals, and gonads) on levels of basic fibroblast
      growth factor (FGF-2) messenger ribonucleic acid (mRNA) in the anterior pituitary
      and the hypothalamus of male rats using RNase protection assays. Castration
      significantly reduced the levels of FGF-2 mRNA in the anterior pituitary, but not
      in the hypothalamus. This decrease was restored by testosterone administration.
      The regulation of pituitary FGF-2 mRNA involves a specific hormone, i.e.
      testosterone, since neither adrenalectomy nor chemical thyroidectomy affects the
      expression of the gene for FGF-2.

PMID- 7803044
TI  - Secretion of transforming growth factor alpha and expression of its receptor in
      human mammary cell lines.
AB  - The secretion of transforming growth factor alpha (TGF alpha) and the expression
      of cell-surface receptors for epidermal growth factor (EGF) were measured in a
      series of human mammary cell lines. The amount of TGF alpha secreted by the cells
      did not correlate with the phenotype of the cells (epithelial or myoepithelial),
      the mechanism of immortalization of the cells (SV40 or spontaneous) or the source
      of the cells (normal mammary gland, benign hyperplastic lesion, malignant
      tumour). The level of expression of cell-surface receptors for EGF was markedly
      increased as a consequence of SV40-immortalization of mammary cells, but
      otherwise did not correlate with the phenotype of the cells or the source of the
      cells. Much of the increase was accounted for by the appearance of a large number
      of low-affinity receptors for EGF in the SV40-immortalized cells. It is suggested
      that one of the mechanisms whereby SV40-immortalization suppresses the senescence
      of primary cultures of human mammary epithelial cells involves increasing the
      level of expression of receptors for EGF. In contrast the level of secretion of
      TGF alpha by cells in culture is probably a consequence of the mechanisms of
      adaptation of each cell line to culture conditions, and does not reflect the
      level of secretion of TGF alpha by cells in vivo.

PMID- 7803045
TI  - Differentiation of Y79 retinoblastoma cells with pigment epithelial-derived
      factor and interphotoreceptor matrix wash: effects on tumorigenicity.
AB  - We investigated the in vivo differentiation potential of Y79 human retinoblastoma
      cells following pre-treatment with two novel neurotrophic agents: PEDF (human
      recombinant pigmented-epithelial derived factor) or IPM (interphotoreceptor
      matrix) wash. These agents were able to induce a significant degree of
      morphological differentiation in vitro. However, 48 days after subretinal
      transplantation of pre-treated cells, massive tumor formation was apparent. In
      contrast, Y79 cells pre-treated with retinoic acid/sodium butyrate, which attain
      a lesser degree of morphological differentiation, did not produce tumors over a
      30 to 60 day-survival time (del Cerro et al., Brain Research, 12-22, 1992). We
      conclude that for PEDF and IPM, the degree of in vitro differentiation and the
      degree of mitotic arrest are independent features.

PMID- 7803047
TI  - [Neurology and the primary health care system].

PMID- 7803046
TI  - The role of PDGF-BB on the development of the collateral circulation after acute
      arterial occlusion.
AB  - The survival of tissues in the presence of arterial occlusion is critically
      dependent on the development of collateral blood vessels. Identification of the
      biochemical mediators and their mechanism of action is fundamental to an
      understanding of the evolution of the collateral circulation. The ability of PDGF
      BB to promote this was evaluated in an animal model of hind limb ischaemia. In
      order to obtain significant quantities of this mitogen for use in our animal
      model, human recombinant PDGF-BB was expressed in a Chinese Hamster Ovary (CHO)
      cell line. The transfected CHO cells produced 544 micrograms/l of PDGF-BB in
      serum free medium (SFM). The 30 kDa form of PDGF-BB was purified to homogeneity
      as judged by silver staining and amino-acid sequencing. Purified PDGF-BB was
      shown to be bioactive by a cell proliferation assay. The exogenous administration
      of PDGF-BB enhanced the recovery of blood flow after acute arterial occlusion.
      The results suggest that PDGF-BB may have therapeutic value in promoting
      collateral development following arterial occlusion.

PMID- 7803048
TI  - [Patient care in a hospital based unit for treating Parkinson's disease and
      movement disorders: a 3-year prospective study].
AB  - A register covering a 3-year period (1991-1993) was opened for all patients
      attending a Parkinson's disease and movement disorder clinic which has been
      running for 15 years in a reference hospital covering a population of 629,555 in
      Madrid. During the last 2 years, all 5 neurologists serving the reference health
      area joined to the hospital on a part-time basis. A total of 764 patients were
      seen during the study period, 56.2% of whom were follow-up patients. About half
      of the later (49%) were suffering from Parkinson's disease (PD), follow-up
      duration averaging 4.7 +/- 4.4 years. Follow-up in dystonias (11.8%) and choreas
      (8.1%) cases was similar and averaged 5.0 +/- 4.2 and 4.5 +/- 4.2 years,
      respectively. Out of 334 new referrals 192 were new parkinsonism patients, half
      of them (48.4%) with secondary parkinsonism, particularly drug-induced
      parkinsonism (32.2%). Incorporation of neurologists serving the reference health
      area to hospital activities correlated to a decrease in secondary parkinsonism
      referrals, a slight drop in de novo PD patients, but not in an earlier detection
      of new PD cases. We conclude that a monographic out-patient clinic may benefit
      from sharing activities with neurologists serving the referral health area, and
      from improving the neurological education of general practitioners.

PMID- 7803049
TI  - [Clinical and investigative approaches in mitochondrial diseases. A review of 15
      cases].
AB  - The results of laboratory investigations in concerning 15 patients suspected of
      mitochondrial disease (MD) are presented. Our purpose is to provide an outline of
      the investigative modalities that support the clinical suspicion and have been
      found to be useful in the diagnosis. Five clinical groups were studied including
      5 exercise intolerances (2 with inflammatory myopathy), 3 with myopathies (1 with
      dilated cardiomyopathy), 2 with progressive external oftalmoplegia (1 associated
      with cerebellar ataxia+epilepsy+hypertrophic cardiomyopathy+pes cavus), 4 with
      encephalopathies (3 with myoclonic encephalopathies with ataxia and dementia and
      1 with epilepsy and tremor), and 1 with metabolic acidosis and cardiomyopathy. We
      used the following categories of investigative procedures: clinical phenotype
      analysis including pedigree study, neurophysiological tests, bicycle ergometric
      evaluation, neuroimaging, microscopic study of skeletal muscle biopsy, post
      mortem examination, biochemical assays and molecular genetic studies. EMG showed
      myopathic changes in 5 cases, features of neuropathy in 2, mixed myopathic and
      neuropathic pattern in 1 and nonspecific changes in 3. EMG was normal in 3
      patients. The most common skeletal muscle abnormalities were variation in fiber
      size (60%), lipid inclusions (33.3%), oxidative subsarcolemmal aggregates (26.7%)
      and ragged-red fibers (26.7%). Electron microscopy revealed mitochondrial
      abnormalities in 8 out of 14 patients' muscle biopsies, and in myocardiac and
      hepatic tissues of another. Site of biochemical defect was located in 12
      patients. Complex I defect in 6, complexes I+IV deficiencies in 3, complex II
      defect in 1, complex IV deficiency in 1, complexes II+IV deficiencies in 1, and
      complex III defect in 1. In 2 patients the biochemical defect was not located.
      Mitochondrial DNA alterations were not found in 7 investigated patients. The
      clinical spectrum of MD has become increasingly wider. After the clinica
      suspicion, the diagnosis depends up on the appropriate use of skeletal muscle
      biopsy, biochemical investigations and molecular genetic techniques. Conventional
      EMG and automatic measurement of the electromyogram are particularly helpful in
      confirming the clinical suspicion in patients with predominantly central nervous
      system disease or in cases in which clinical signs are few.

PMID- 7803050
TI  - [Silent myocardial ischemia in patients with transient ischemic attacks].
AB  - Given evidence that ischemic heart disease is the most frequent cause of death in
      patients with cerebrovascular disease, we used ergometrics to screen 80 patients
      with TIA for silent myocardial ischemia (SMI) at the neurological unit of
      Hospital Clinico Universitario in Zaragoza, Spain. The patients were compared
      with a control group of 80 with no signs of heart disease. Neither the patients
      nor the controls had ever shown clinical signs of coronary ischemia and their
      baseline electrocardiograms were normal. Stress test results were positive in 25
      (31%) of the TIA patients, and in 4 (5%) (p < 0.001) of the controls, showing
      that the prevalence of SMI is significantly higher in TIA patients than in the
      general population. Hiperlipidemia (75% testing positive versus 43% negative, p <
      0.01) and diabetes (31% testing positive versus 13% negative, p < 0.01) were the
      risk factors statistically related with a positive stress test.

PMID- 7803051
TI  - [DNA instability and neurological diseases: a new model for genetic disease].

PMID- 7803052
TI  - [Sumatriptan ++].

PMID- 7803053
TI  - [Carotid artery dissection at the cervical level presenting as unilateral paresis
      of lower cranial nerves].
AB  - Internal carotid artery dissection at the cervical level is a known cause of
      stroke in young patients. The usual clinical presentation is strong ipsilateral
      cephalea and oculosympathetic paresis or ischemic symptoms in the affected
      artery. Paresis of the lower cranial nerves due to local compression in the space
      behind the parotid is rarely found and may complicate the diagnosis by leading
      physicians to look for anomalies in the vertebro-basilar territory. We present a
      patient with internal carotid artery dissection at the cervical level diagnosed
      by angiography. Symptoms at presentation were hemicranial cephalea accompanied by
      Villaret's syndrome. We point out the importance of keeping this diagnostic
      possibility in mind when looking for the etiology of subacute paresis of the
      lower cranial nerves.

PMID- 7803054
TI  - [Alien limb behavior associated with Alzheimer's disease].
AB  - A 48-year-old female developed apraxia, followed by aphasia and dementia.
      Clinical examination also showed an alien member sign, supranuclear gaze paresis,
      myoclonus and rigidity on the right arm. The examination of the frontal lobe
      biopsy showed typical lesions of Alzheimer's disease as the only
      neuropathological abnormality. The association of this clinical syndrome with
      Alzheimer's pathology is unusual.

PMID- 7803055
TI  - Progressive bleeding in spontaneous thalamic hemorrhage.
AB  - Progressive bleeding is uncommon in spontaneous intracerebral hemorrhage. We
      describe two cases of spontaneous thalamic hemorrhage with evidence of active
      bleeding or rebleeding detected by noncontrast CT. The first patient was a 47
      year-old man with a history of hypertension and cocaine abuse. The second
      patient, a 73-year-old man, had no valuable risk factors. It is noteworthy that
      most well-documented instances of continued bleeding or rebleeding in spontaneous
      intracerebral hemorrhage occur in the thalamus. The natural evolution of
      spontaneous intracerebral hemorrhage after the first hours of stroke remains to
      be elucidated.

PMID- 7803056
TI  - [Posterior cortical dementia].
AB  - Two patients, aged 59 and 73 years, presented with the clinical syndrome of
      Posterior Cortical Dementia (PCD). Follow-up during 3 and 11 years confirmed the
      progressive nature of the disorder. Posterior cerebral impairment was seen on
      SPECT studies. Neuroimaging studies showed an early dilatation of the right
      occipital ventricular horn which predominated over the cortical atrophy. This
      kind of cerebral atrophy could identify a subset of PCD cases that may be
      unrelated to Alzheimer's disease.

PMID- 7803057
TI  - [Is migraine with onset in adulthood a risk factors for myocardial infarction?].

PMID- 7803058
TI  - [Polyarteritis nodosa, multiple mononeuritis and cryoglobulinemia].

PMID- 7803059
TI  - [Peripheral neuropathy and mixed cryoglobulinemia].

PMID- 7803060
TI  - Levels and trends in blood pressure and prevalence and treatment of hypertension
      in The Netherlands, 1987-1991.
AB  - Levels and trends in blood pressure (BP), as well as prevalence and treatment of
      hypertension, were studied in The Netherlands between 1987 and 1991. BP was
      measured continuously using a standardized method in 36,273 men and women 20-59
      years of age. The data were weighted for the age distribution of the general
      Dutch population in 1990 and adjusted for each technician who measured BP. In
      summer in both men and women, systolic blood pressure (SBP) was about 1.5-2.0 mm
      Hg lower than in the other seasons, and diastolic blood pressure (DBP) was 0.5
      1.0 mm Hg lower. In 1987 SBP was 124 mm Hg in men and 117 mm Hg in women. DBP was
      78 mm Hg in men and 75 mm Hg in women. The prevalence of hypertension was 8% in
      both men and women. Between 1987 and 1991, SBP decreased slightly while DBP
      increased slightly. The prevalence of hypertension did not change in this period.
      The percentage of treated hypertensive men decreased significantly from 44% in
      1987 to 34% in 1991 and from 60% to 49%, in women. We conclude that the
      prevalence of hypertension did not change between 1987 and 1991, yet the
      treatment of hypertension decreased, possibly because of a change in the pattern
      of treatment by Dutch physicians.

PMID- 7803061
TI  - Hypertension in Korea: a national survey.
AB  - To determine the prevalence of hypertension (HTN) and its risk factors, we
      performed a population-based national cross-sectional blood pressure (BP) survey
      in Korea in 1990. Through cluster sampling, we selected for study individuals
      older than 30 years of age in 190 of 154,082 districts. Among 25,567 eligible
      individuals, 21,242 subjects had measurements of BP and body mass index (BMI) and
      underwent a standard interview. BP was recorded as the mean of two measurements
      on a standard mercury manometer. The prevalence of HTN varied widely by area of
      residence. Overall prevalence was 19.8% for HTN defined as BP > or = 140/90 mm Hg
      or subject on medication, and 12.4% for BP > or = 160/95 mm Hg or subject on
      medication. Correlates for HTN identified by logistic regression analysis
      included positive family history of HTN (odds ratio [OR] = 2.2,), age (10 years);
      OR = 1.9), alcohol intake (500 cc; OR = 1.4), urban location (versus rural; OR =
      1.3), and BMI (1 BMI unit; OR = 1.2). [Am J Prev Med 1994;10:200-4]

PMID- 7803062
TI  - An evaluation of heart health education for Southeast Asians.
AB  - We present data on the effects of a heart health education intervention targeted
      at adult Southeast Asians. Within each of the Cambodian, Laotian, and Vietnamese
      groups who received the intervention, we obtained random samples approximately
      three to 18 months postintervention. Comparisons were made between
      preintervention and postintervention knowledge of blood pressure and awareness of
      behaviors to prevent heart disease. Within all three ethnic samples, we found
      significant increases in the pre-to-post percentages of individuals who could
      define blood pressure and identify ways to prevent heart diseases.

PMID- 7803063
TI  - Putting medical practice guidelines into practice: the cholesterol model.
AB  - As more and more medical practice guidelines are developed in the United States,
      commensurate evaluation efforts should assess their impact on professional
      practice and patient outcomes. We describe an ongoing research program designed
      to develop and test practice models for applying the 1988 Adult Treatment Panel
      Guidelines for the clinical management of high blood cholesterol. Four studies
      are evaluating different models to assist nonacademic community practices in the
      detection, evaluation, and treatment of high blood cholesterol. We have designed
      randomized controlled trials set in solo and small-group primary care practices
      of family or general practitioners and internists situated in rural, suburban,
      and urban settings. Patients include adult men and women who represent diverse
      socioeconomic and ethnic backgrounds. We are measuring rates of cholesterol
      screening; dietary and drug treatment and follow-up; changes in dietary intake
      and compliance with drug therapy; changes in quality of life and cost of
      intervention; and reduction in cholesterol level. Scheduled for completion in
      1994, this program will provide insights into practical and effective methods of
      lipid management. It serves as a model for studying the application of health
      guidelines in the context of nonacademic primary care practices serving diverse
      patient populations.

PMID- 7803064
TI  - Socioeconomic differences among people with AIDS: results from a Multistate
      Surveillance Project.
AB  - To characterize the socioeconomic status of persons with acquired
      immunodeficiency syndrome (AIDS), 11 U.S. state and city health departments
      interviewed 2,898 persons > or = 18 years of age reported with AIDS between June
      1, 1990, and January 31, 1993. Among men who have sex with men, white men
      reported the lowest percentage (9%), and Central/South American (50%) and Mexican
      men (40%) reported the highest percentages not completing 12 years of school.
      Among intravenous drug users (IDUs), 35% of white men, 64% of black men, 67% of
      Puerto Rican men, 29% of white women, and 63% of black women had not completed 12
      years of school. Overall, 77% of the men and 90% of the women were unemployed; we
      also found racial/ethnic differences by employment but to a lesser degree than
      differences in education. Among women, but not among men, differences in
      household income by race and ethnicity were marked; 76% of white and 91% of black
      female IDUs reported a household income of $10,000. Human immunodeficiency virus
      (HIV) prevention programs must be targeted toward the educational level of the
      populations served, and HIV services must adapt to the financial circumstances of
      their clientele.

PMID- 7803065
TI  - Health promotion and disease prevention for older adults: opportunity for change
      or preaching to the converted?
AB  - Health promotion and disease prevention for the elderly offer the potential for
      improving the quality of life for the growing population of older adults, while
      reducing the economic burden on the health system. Whether this potential can be
      realized depends, in part, on whether those older adults whose health behaviors
      put them at risk actually use preventive services when offered the opportunity.
      In 1988 the Health Care Financing Administration began a series of health
      promotion demonstrations to address health issues related to older adults. This
      article reports on program participation at one of the five demonstration sites.
      Over 1,900 community-dwelling Medicare beneficiaries who receive their health
      care through fee-for-service providers were enrolled in the demonstration. These
      enrollees were randomly assigned to control and experimental groups, with the
      latter offered health screening and promotion services. Nine hundred-seventy
      three of the experimental subjects and 938 of the control subjects completed a
      lengthy telephone interview, which determined each person's use of preventive
      services and practices. Although all 973 experimental subjects were invited by
      letter and follow-up telephone calls to attend these free-of-charge, Medicare
      provided sessions, not everyone attended. We analyzed 17 health behaviors of
      those who attended the first session and those who did not. Those engaging in
      these preventive behaviors were neither more nor less likely to attend the
      screening services. Thus, we found neither "favorable" nor "unfavorable"
      selection bias in the use of these preventive services.

PMID- 7803066
TI  - DATA2000: CDC WONDER information system linking Healthy People 2000 objectives to
      data sets.
AB  - To monitor progress on the Healthy People (HP) 2000 objectives, planners and
      researchers will need information on relevant data sources. DATA2000 is a project
      designed to identify these data and link them with objectives and to develop a
      computerized information system providing access to this information. Sources of
      information on objectives and data included Healthy People 2000, catalogs and
      data bases of data sets, and the HP 2000 Steering Committee. We created an
      "assessment" of the utility of the data set for the particular objective. A
      Centers for Disease Control (CDC) WONDER-based information system was developed
      (using methods previously described). We identified 204 data sets and created 408
      assessments. All but one of the objectives were paired with corresponding data.
      Over half the data come from CDC. The CDC WONDER-based information system
      crosslinks the objectives, data sets, and assessments and provides 5-10 pages of
      information about each. Understanding the contribution of prevention will be
      critical in planning reforms of the health care system. DATA2000 can be an
      important resource in this process.

PMID- 7803067
TI  - Use of laboratory reports to assess cervical cancer screening in a community.
AB  - Cancer of the uterine cervix, the sixth most common cancer among women, is still
      considered a significant health problem, despite declining mortality rates during
      recent decades. In Baltimore, the age-adjusted mortality rates for cervical
      cancer are significantly higher than the U.S. average, for both black and white
      women. Early detection of cervical cancer through screening with the Papanicolaou
      (Pap) test has shown to decrease mortality by preventing development of invasive
      disease, and intervention programs have been developed to increase use of Pap
      testing. However, the evaluation of those programs is difficult, as self-reports
      of Pap screening may be inaccurate, and repeated inquiries about Pap tests may
      influence the behavior being studied. We report in this article a method to use
      data from cytopathology laboratories to estimate the use of Pap screening by
      women in a defined population. This approach can be used to evaluate changes in
      receipt of Pap smears and to provide feedback to intervention programs.

PMID- 7803068
TI  - Physicians and medical students: factors affecting entry into public health.
AB  - We surveyed members of a recent master of public health (MPH) degree program to
      learn more about how, when, and why physicians and medical students decided to
      seek formal training in public health. We interviewed physicians and medical
      students to determine how and why these MPH students became involved in what they
      considered public health work; how and why they decided to attend public health
      school; and what their career plans were following completion of the degree
      program. All 47 medical students and physicians responded to the survey. Sixty
      six percent described previous public health-related work experience. Only 5%
      decided prior to or during college to attend public health school. A personal
      contact directed 62% towards public health school. Those with previous public
      health work experience were more likely to pursue what they considered public
      health careers after completion of public health school than those without such
      previous work experience. The continuing need for qualified practitioners and
      leaders in public health challenges the medical community to characterize further
      those factors motivating medical students and physicians to formalize their
      training in public health.

PMID- 7803069
TI  - Developing a competency-based preventive medicine curriculum for medical schools.
AB  - Trends in patient morbidity and mortality, cost-effectiveness, and national
      recommendations mandate that we practice more preventive medicine. To address
      this need, we set out to develop a comprehensive curriculum in preventive
      medicine for medical schools. We constructed a competency-based (i.e.,
      performance-based) curriculum with specific educational objectives defined by
      outcomes. Subject areas were subdivided by life stages, and learning objectives
      were created separately for epidemiology, assessment, and intervention. We hope
      that adoption of such an educational blueprint by medical schools will measurably
      enhance the attitudes, knowledge, and skills necessary for the incorporation of
      preventive principles into all aspects of clinical medicine.

PMID- 7803070
TI  - MRI of selected sports injuries: muscle tears, groin pain, and osteochondritis
      dissecans.
AB  - This article discusses three selected areas of sports medicine in which MRI is
      useful. The first is muscle injuries and includes the MRI findings in muscle
      tears, contusions, and myositis ossificans. The second section discusses the
      usefulness of MRI in imaging the athlete with groin pain, which is a difficult
      clinical problem for the orthopedist. The ability of MRI to differentiate between
      such causes of groin pain as osteitis pubis, bursitis, and stress fractures is
      shown. The final section covers plain radiographic and MRI findings in
      osteochondritis dissecans. Also discussed is the MRI staging of osteochondritis
      dissecans, which is important in treatment decisions and surgical planning.

PMID- 7803071
TI  - MRI of the shoulder.
AB  - MRI of the shoulder is widely considered the imaging modality of choice in the
      evaluation of shoulder pain and the clinical impingement syndrome. This is
      because of its direct evaluation of all of the soft tissue structures of the
      subacromial space, as well as its ability to depict the relationship of the
      overlying osseous and soft tissue structures of the coracoacromial arch. It also
      provides information regarding the capsulolabral anatomy and, with the addition
      of MR arthrography, is becoming recognized as the imaging modality of choice for
      instability workup. MRI evaluation, when combined with the always important
      clinical history, physical examination, and radiographs, provides the referring
      clinician and orthopedic surgeon with the most anatomic and pathological
      information possible. This, in turn, allows the most informed decision making
      possible regarding conservative management or surgical treatment.

PMID- 7803072
TI  - MRI of knee ligaments.
AB  - The stability of the knee depends on the integrity of its ligaments. Pain,
      clinical history, and nonspecific physical findings may hinder clinical diagnosis
      of acute ligamentous injury. Most major knee ligaments have uniform low signal
      intensity on all imaging sequences, and diagnosis of injury is based on
      periligamentous soft tissue edema, increased signal within the ligament, or
      disrupted structures. Correlation of of findings from routine sagittal, coronal,
      and axial MRI scans usually yields a definitive diagnosis of knee ligamentous
      injury. This article reviews normal anatomy, function, mechanism of injury, and
      normal and pathological MRI findings of the major knee ligaments.

PMID- 7803073
TI  - MRI of the patellofemoral joint.
AB  - In routine MRI of the knee, less attention frequently is paid to the
      patellofemoral joint and its surrounding structures than to the menisci and
      ligaments. This article reviews MRI of common abnormalities of the anterior
      aspect of the knee. Chondromalacia patellae, pathological softening of the
      patellar cartilage, can be diagnosed with reasonable accuracy with MRI using
      standard sequences. Abnormalities of alignment can be assessed grossly on static
      images, but more sophisticated evaluation of patellofemoral tracking requires the
      kinematic technique. Other traumatic or overuse injuries involving the extensor
      mechanism of the knee, such as the quadriceps and patellar tendons, are also
      reviewed briefly.

PMID- 7803074
TI  - Bone bruises: their patterns and significance.
AB  - MR imaging is sensitive in the detection of occult stress and posttraumatic
      fractures in and around the knee joint. In some patients, the pain from these
      bony injuries can mimic that of meniscal tears. The abnormality of the bone may
      explain completely the patient's symptoms and obviate the need for any further
      work-up. The types of injuries detected by MRI include bone bruises, stress or
      insufficiency fractures, and osteochondral fractures. Bone bruises or contusions
      are characterized by a diffuse or localized pattern of low signal intensity on T1
      weighted images without a defined fracture. Blood, edema, hyperemia, and perhaps
      microfracture of the trabeculae may all contribute to the marrow signal
      alterations. Anterior cruciate ligament injuries often are accompanied by a
      characteristic bone contusion pattern, such as hemorrhage or edema in the
      posterior aspect of the lateral tibial plateau, as well as the anterior aspect of
      the lateral femoral condyle.

PMID- 7803075
TI  - MRI of the ankle and hindfoot.
AB  - MRI of the ankle and hindfoot has become a widely used diagnostic test. The major
      indications for MRI of this region are disorders of tendons and bones. Avascular
      necrosis is common in the foot, usually seen after talus fractures or
      spontaneously in the metatarsal heads. Other causes of a marrow edema pattern
      include occult fractures, arthritic disorders, reactions to altered biomechanics,
      osteomyelitis, and regional migratory osteoporosis. The most frequently diseased
      tendons in the ankle are the Achilles, posterior tibial, and peroneal. MRI can be
      used to diagnose most disorders of these tendons, as well as stage these
      disorders to allow appropriate therapy. Most of these tendon disorders follow a
      recognized sequence of progression using the Achilles tendon as a model.

PMID- 7803076
TI  - [The prognostic value of brain CT scan in infants with periventricular
      leukomalacia].
AB  - Brain CT scan was performed at 40 weeks of conceptional age in 17 preterm infants
      with periventricular leukomalacia (PVL). The finding of periventricular low
      density was not useful in differentiating patients with PVL from normal infants,
      because this finding was seen in 40% of normal infants. The following findings
      were characteristic of PVL: (1) a marked low density area in centrum semiovale,
      (2) an irregular outline of ventricular wall, and (3) low density spots in
      periventricular white matter. The findings of ventricular dilation with irregular
      wall and marked low density area in centrum semiovale were correlated with a
      finding of volume loss on MRI during late infancy and the severity of
      neurological impairment, especially in severely affected patients. Marked low
      density area in centrum semiovale was characteristic of severe PVL demonstrated
      on brain CT scan.

PMID- 7803077
TI  - [Development of the brainstem and cerebellum in autistic children].
AB  - Studies of magnetic resonance images have revealed morphological disorders of the
      brainstem and cerebellum in autistic children and adults. When we studied
      development of the brainstem and cerebellum in autistic patients, these
      structures were significantly smaller in autistic patients than in controls.
      Although the brainstem and cerebellum significantly increased in size with age in
      both groups, the development of the pons, cerebellar vermis I-V and cerebellar
      vermis VI-VII was significantly more rapid in autistic patients than in controls.
      However, the development of the other brain structures in the posterior fossa did
      not differ between autistic patients and controls. The regression intercepts of
      the brainstem and cerebellum as well as those of their components were
      significantly smaller in autistic patients than in controls. These results
      suggested that significant anatomical changes took place in the posterior fossa
      brain structures in the prenatal period in autistic children, but were not
      progressive.

PMID- 7803078
TI  - [Epilepsy in patient with structural autosomal abnormality].
AB  - Few cases have been reported on the structural autosomal abnormality (SAA)
      focusing on epilepsy excluding those of Down syndrome and Klinefelter syndrome.
      We investigated patients who had SAA with special reference to epilepsy. Various
      types of epilepsy were observed in its severity in our cases as well as
      previously reported cases. There was no correlation between the degree of mental
      retardation, motor dysfunction, brain damage on CT scan, and severity of
      epilepsy. Some cases had brain dysplasia, such as agenesis of corpus callosum,
      pachygyria, and mega cisterna magna. No correlation was found between these brain
      dysplasia and severity of epilepsy. It is important for a pediatrician to find a
      common epileptic syndrome or EEG abnormality in a SAA. An observation of symptoms
      in patients with the same chromosomal deletion or duplication will lead to
      identification of responsible gene for an epileptic symptom.

PMID- 7803079
TI  - [Five cases of phosphorylase b kinase deficiency affecting muscle or liver:
      clinical symptoms and diagnosis].
AB  - Muscle, erythrocyte and/or leukocyte phosphorylase b kinase (PBK) activities were
      measured in 5 patients and in 2 families. The relation between phenotype and
      enzyme deficiency in clinically variable samples based on measurement of
      erythrocytes, leukocytes or muscle was described. Three patients showed the
      enzyme deficiency in liver and the disease was transmitted as an X-linked
      recessive trait. In these cases, our results suggested that carrier detection was
      more reliable with erythrocytes than leukocytes. Two patients showed enzyme
      deficiency in muscle, and the mode of inheritance was not clear. In these cases,
      muscle biopsies were necessary for diagnosis.

PMID- 7803080
TI  - [Motor developmental screening test for mental retardation: evaluations of
      sensitivity and specificity].
AB  - For the purpose of early detection and early habilitation for developmentally
      handicapped children, we started medical screening for pediatric neurological
      diseases among children in Sodegaura City, Chiba prefecture, since 1978. We
      calculated sensitivity, the rate of judging abnormal children to be abnormal,
      specificity, the rate of judging normal children to be normal and positive
      predictive values, the rate of judging abnormal children who have abnormal sign,
      of sitting alone at nine months of age whether an infant is MR or not. The
      sensitivity was 70.0%, the specificity was 98.3% and the positive predictive
      value was 26.5%, all of them were high rates. Therefore we conclude that children
      who can not sit alone until nine months of age are possibly mentally retarded and
      the capability of sitting alone or not at nine months of age is an useful
      screening test for the purpose of early detection of mentally retarded children.

PMID- 7803081
TI  - [A study of children with cerebral palsy who were born between 1977 and 1985 in
      Kyoto City; a report from an institution for handicapped children].
AB  - First, we longitudinally analyzed 177 cerebral-palsied children (CP) who were
      born in Kyoto City between 1977 and 1985. They were all visited St. Joseph
      Hospital for Crippled Children in Kyoto during the period 1977 to 1991 in order
      to investigate the relationship between the prognosis of perinatal care and the
      changing panorama of CP in Kyoto. The average occurrence rate of CP per 1,000
      live birth during the 9 years in Kyoto was 1.12. 177 CP were divided into 3
      groups according to their birth years: 1977-1979 (47 CP); 1980-1982 (62 CP); and
      1983-1985 (68 CP). Then we compared the distribution of birthweights and
      gestational periods among the 3 groups. We found a significant increasing trend
      in the percentage of CP in babies with birthweight less than 2,000 g. Second, we
      examined 162 CP; 15 born outside of Kyoto were excluded because of extraneous
      influences of perinatal care. 162 were divided into 3 groups according to their
      birth years: 1977-1979 (44); 1980-1982 (56); and 1983-1985 (62). We also compared
      the risk factors and prognosis according to the birthweights and gestational ages
      among the 3 groups. This study revealed a decreasing trend in the frequency of
      convulsions of full term CP, dyspnea and oxygen administration of premature CP in
      the neonatal period. At the same time, the motor development of CP without mental
      retardation had improved significantly in the later period. However, in the last
      3 years the distribution of the severity of motor disturbance at 4 years of age
      among CP with birthweight of 1,000-2,000 g was either mild or severe.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7803082
TI  - [A case of pontine hematoma with Foville's syndrome in childhood].
AB  - We reported a surviving case of 6-year-old boy with pontine hematoma. He
      complained of headache as an initial symptom and developed progressively
      Foville's syndrome with impairments of the IX-XII cranial nerves. Although
      brainstem tumor was suspected initially using CT scan, MRI revealed the existence
      of hematoma in the ventromedial pons. During the first 4 months of his clinical
      course, Gd-DTPA did not demonstrate any enhancement in that lesion. However,
      hemangiomatous lesion was suspected by subsequent serial MRIs with positive Gd
      DTPA enhancement. Using conservative treatment including oral corticosteroids,
      all the neurological deficits disappeared in several months and he did not show
      any recurrence of clinical signs for 3 years. It was suggested that MRI was very
      useful in the differential diagnosis and the follow-up of hematoma in the
      posterior fossa.

PMID- 7803083
TI  - [Hypomelanosis of Ito associated with hemimegalencephaly].
AB  - A girl aged 1 year and 2 months with hypomelanosis of Ito was reported. She
      suffered from intractable epileptic seizures since the second day after birth.
      Characteristic bizarre hypopigmented skin lesions were seen on her left shoulder
      and extended in a linear fashion to the flexion side of the left upper extremity.
      Brain MRI revealed diffuse enlargement of the left hemisphere, dilatation of the
      left lateral ventricle, and neuronal migration anomalies, indicating
      hemimegalencephaly. The types of her seizures were secondarily generalized or
      unilateral initially, followed by infantile spasms at 1.5 month. Around 4 months
      of age, frequent partial seizures appeared. Her seizures were intractable despite
      vigorous anticonvulsant therapy. As patients with hypomelanosis of Ito are
      frequently associated with neurological abnormalities, brain MRI studies were
      thought to be essential in detecting central nervous system anomalies,
      particularly in the presence of early onset intractable seizures.

PMID- 7803084
TI  - [A case of hemimegalencephaly: ictal EEG and SPECT].
AB  - A case of 1-month-old female infant with hemimegalencephaly was reported. This
      disorder is a rare malformation characterized by congenital hypertrophy of one
      hemisphere and ipsilateral ventriculomegaly. Clinical signs of the patient
      included a left sided macrocephaly, intractable seizures and delayed development.
      Ictal single photon emission computed tomography (SPECT) on the 49th day using
      99mTc-HMPAO showed hyperperfusion in the left occipital and frontal lobes, when
      ictal EEG showed a sharp wave-burst appearing continuously in the left occipital
      lobe that spread to the left frontal lobe. Interictal SPECT on the 48th day
      demonstrated and increased tracer accumulation in the left hemisphere, especially
      in the left frontal lobe. In this case, the megalencephalic hemisphere might have
      an important role for epileptogenesis and its spread according to the ictal SPECT
      findings.

PMID- 7803085
TI  - [Childhood-onset neuropathy associated with elevated serum antibody against GM 1
      ganglioside].

PMID- 7803086
TI  - [Clinical application of YAG laser in nasal endoscopic surgery].
AB  - In this study, we assessed the value of the clinical application of YAG laser in
      32 cases of nasal endoscopic surgery. It was found that the operation performed
      under the nasal endoscope with YAG laser has several advantages including less
      bleeding, clear observation, simplified performance, thorough excision and less
      postoperative pain. But it also has some disadvantages, such as laser-induced
      lesion in the surrounding normal tissues, easy pollution and damage of the opto
      guide fiber.

PMID- 7803087
TI  - [Clinical significance of intraoperative frozen biopsy of cervical lymph node for
      laryngeal cancer].
AB  - The results of intraoperative and postoperative pathologic examination in 102
      cases of laryngeal cancer were reported. The overall consistent rate of
      intraoperative and postoperative biopsy was 114/116(98%). The consistent rate of
      positive result was 40/40(100%), while the consistent rate of negative result was
      74/76(97%). The pathological and clinical results showed that the intraoperative
      frozen biopsy could confirm the metastasis of cervical lymph node. When frozen
      biopsy was positive, the neck dissection should be performed. When frozen biopsy
      was negative, the neck dissection should not be performed in most cases, or the
      functional neck dissection may be performed in some cases.

PMID- 7803088
TI  - [Repair of the traumata caused by partial laryngectomy].
AB  - At present, the wound caused by partial laryngectomy are repaired by using many
      kinds of tissues in order to avoid infection, granuloma and laryngeal stenosis.
      It is unclear whether the traumata has to be repaired by transplant tissues or
      non-repaired traumata will lead to laryngeal dysfunction. This article analyzed
      162 patients who received partial laryngectomy from April 1980 to March 1992.
      These patients had been divided into two groups: repaired group (78 cases) and
      non-repaired group (84 cases). Repair material used included sternohyoideus
      fascia (57 cases), thyro-hyoideus fascia (9 cases), throat musculus flap (6
      cases), stemocleido-mastoideus fascia (3 cases) and throat flap (3 cases). The
      result indicated that there were no significant differences in respiration
      swallow recovery time and so on. So we concluded that non-repaired group has
      similar curative effect to repaired group and repairing the traumata (especially
      minor traumata) with the fascia around the traumata is an effective method.

PMID- 7803089
TI  - [Study on deglutition function following total laryngectomy, epiglottoplasty and
      reconstruction of vocal function].
AB  - Twenty-five cases of epiglottoplasty after total laryngectomy were summarized.
      Only 4 cases presented aspiration for a short period of time. The X-ray films
      were taken using a cinematograph X-ray unit and a telecontrol X-ray unit. The
      results demonstrated that in non aspirator cases and 1 healthy man, the tongue
      and the larynx (or reconstructive new larynx) coordinated closely and there was
      better glossolaryngeal close-knit degree, but in aspirator cases there was no
      coordination between them. The study proved that the deglutition a coordinative
      motion of hyoid muscles, laryngeal muscles and the nerves supplying them. So it
      is important that the hyoid bone, its superior muscles and pharyngeal
      constrictors should be preserved during the operation.

PMID- 7803090
TI  - [Hydroxyapatite for laryngotracheal framework reconstruction].
AB  - This paper reported combined sternohyoid myocutaneous flap and hydroxyapatite
      (HA) graft for laryngotracheal reconstruction in clinical and experimental
      studies. HA rings were employed for reconstructing the laryngotracheal framework
      in 10 patients on the base of animal experiment. The implant was well taken in
      all cases without any rejection, resulting in excellent airways. The study
      demonstrates that this procedure can be used in treatment of severe
      laryngotracheal stenosis.

PMID- 7803092
TI  - [Study on the bilaterally recorded ABR in the experimental model of acoustic
      tumor].
AB  - The ABRs were bilaterally recorded with monaural stimulation from the animal
      model of acoustic tumor in 10 rats. It was found that the waveform of ABRs
      recorded from the right dura was different from the left one. A major feature of
      right ABRs was that the amplitudes of wave II and wave III were decreased by 3.53
      +/- 1.21 microV and 3.94 +/- 1.16 microV respectively, and that the latencies of
      wave IV and wave V were increased by 0.88 +/- 0.11ms and 1.37 +/- 0.10ms
      respectively. It suggested that the cochlear nerve near the cochlear nucleus was
      pressured. A major feature of left ABRs was that the amplitudes of wave III were
      prominently reduced by 7.02 +/- 0.73 microV and wave IV and V were mixed
      together. The results implied that the waves generated after wave III might be
      affected by the bilateral auditory pathway.

PMID- 7803091
TI  - [Study of topographic mapping of the auditory middle latency response in the
      guinea pigs].
AB  - Topographic mapping techniques were applied to study the auditory middle latency
      response (MLR) in 10 awake guinea pigs. Fourteen holes (1mm in diameter) were
      drilled through the skull regions and epidural electrodes were fixed on the skull
      with the dental cement, then auditory MLR were recorded with 13 electrodes, and
      MLR brain maps were obtained with a concerto system. Our result supports the
      hypothesis of multiple MLR generators. The main components are wave A, wave B and
      wave C. The foci localise the temporal lobe contralateral to the stimulated ear.
      The other components are wave M- and wave M+. The foci localise parietal and
      occipital lobes. Each wave responds differently to procaine. The result suggests
      that wave A, wave M- and wave M+ are generated from the subcortex, while wave B,
      wave C generated from the cortex.

PMID- 7803093
TI  - [The changes in the summating potential and morphology in the cochlea of guinea
      pigs with anoxia].
AB  - The dynamic changes in the CAP, SP and EP in the scale media were examined with
      single micropipet during anoxia and reventilation with oxygen. Also, the
      morphologic changes in the IHC, OHC and synapse were observed in this experiment.
      It was found that the amplitude of the SP and EP values declined with alteration
      in polarity of these value. The changes in polarity and amplitude of the SP
      followed the changes of CAP threshold induced by anoxia. The histologic
      examinations revealed no evidence of acetylcholinesterase (AChE) alteration in
      the synapse and no succinic dehydrogenase (SDH) changes in IHC appeared. However,
      the activity of SDH in the OHC decreased. The results suggest that the polarity
      and amplitude of SP were influenced passively by the changes of EP value. In
      addition, the changes of SP polarity from positive to negative during anoxia is
      due to the loss of modulation process of OHC to IHC, while the SP polarity from
      negative to positive during the supply of oxygen is caused by regain of the
      modulation process of OHC.

PMID- 7803094
TI  - [Evaluation of posttraumatic hearing loss].
AB  - In this study a comprehensive audiometry was applied to detect the hearing loss
      in 400 patients (531 ears) with difficult-to-test hearing loss induced by ear or
      skull injury. It was found that the real PTA detectable rate reached 95.29% and
      the incidence of hearing loss was 82.11%, of which 68.81% were related to injury.
      The incidence of nonorganic deafness was 77.59%, i.e., the incidence of hearing
      loss exaggerated by patients was 57.25% (tested ears), simulated deafness was
      16.20% and functional deafness was 4.14%. The principle of dealing with
      nonorganic deafness was discussed.

PMID- 7803095
TI  - [Study on the use of multiple choice type test of speech audiometry in Shanghai
      area].
AB  - Using the speech audiometry material worked out by Sheng Ye et al, we performed
      multiple choice tests on 20 medical students with normal hearing in an attempt to
      prove the practicability of this material in Shanghai dialect area. The results
      showed that the equilibrium of the standard Chinese pronunciation word-lists used
      in Shanghai is not as good as in Beijing. Equilibrium calibration is necessary
      for Shanghai subjects. Meanwhile, the educational level and psychological state
      of the subjects and environment of the test may affect the results of the test.
      Thus a detailed explanation of this method and a pretest with exercise word-list
      are very important. The results indicate that multiple choice type test of speech
      audiometry is applicable to the comparison of the hearing level of the same
      subject and is useful in hearing-aid fitting.

PMID- 7803096
TI  - [Hair cell damage and regeneration in the quail cochlea following kanamycin
      ototoxicity].
AB  - Forty-day old quails were given kanamycin (KM) at a dose of 400mg/kg per day for
      ten days. Evoked potential thresholds induced by both click and tone burst were
      obtained at 1 day or 1, 2, 3, 4 and 6 weeks respectively after the last
      injection, and compared with the thresholds of age-matched control animals. The
      cochlea of the animals was examined by scanning electron microscopy (SEM). The
      results showed that the application of KM for 10 days produced massive
      destruction of the basilar papilla at 1 day posttreatment. The damaged region
      began at the base and extended apically to the position about 50-70% of the total
      distance along the papilla, with most severe damage in the basal end. The
      auditory thresholds measured at the same time revealed a significant elevation at
      2 and 4 kHz. However, the number of hair cells in the damaged region recovered
      rapidly with time, and so did the function. By the end of 3 weeks postinjection,
      almost all the hair cells reappeared in the pathologic region and the function
      improved further, with nearly normal thresholds at all frequencies but 4kHz. Six
      weeks after KM treatment, the basilar papilla showed a nearly normal appearance,
      but there was no further functional improvement at 4kHz, with the threshold shift
      by 17.5 dB (P < 0.01). The results of the present study demonstrated that
      structural recovery was faster than functional one.

PMID- 7803097
TI  - [Hair cell regeneration and recovery following gentamicin induced damage in the
      chick cochlea].
AB  - Two-day old chicks were given gentamicin (GM) and kanamycin (KM) for 10 days and
      then the cochleas were processed for both scanning electron microscopy and light
      microscopy on the same day and in 1, 2, 3, and 4 weeks following the last
      injection to examine hair cells regeneration and recovery. The result showed that
      hair cell loss was up to 40% in the base of the basilar papilla following GM and
      KM administration. One week after injection, however, most of the damaged region
      was replaced with regenerated hair cells. Three to four weeks later, the
      regenerated hair cells were developed into normal sensory hair cells. This
      experiment demonstrated that the hair cells in the chick cochlea were able to
      regenerate and recover following GM and KM induced damage.

PMID- 7803099
TI  - [The influence of obliteration of external lymphatic space on the vestibule and
      the cochlea in guinea pigs].
AB  - Obliteration of the external lymphatic space on 18 guinea pigs was performed. The
      lymphatic space of the horizontal semicircular canal was blocked by fascia.
      Auditory (ABR) and vestibular functions were tested before and after the surgical
      obliteration. Morphologic changes in the cochlea and vestibule were observed
      under light microscope. It was found that there was no significant difference in
      the threshold of ABR before and after the operation. However, the sustained time
      of nystagmus was significantly decreased after the operation. Our results
      indicate that this surgical procedure may damage vestibular function, but produce
      no evident damage to the cochlear function.

PMID- 7803098
TI  - [Study on Na(+)-K(+)-ATPase of the spiral ganglion neuron and
      acetylcholinesterase of the cochlea efferent nerve after electric stimulation in
      the scale media].
AB  - In this study, it was found the concentration of Na(+)-K(+)-ATPase of the spiral
      ganglion neuron (SGN) increased 3 months after electric stimulation (0.1 mA) for
      3 hours. However, current at 1.0 mA would destroy the enzyme production mechanism
      of SGN. Therefore 0.4 mA might be thought as a critical level because the
      concentration of the enzyme decreased with just above this level of stimulation.
      We suggest that the appropriate intensity range of the current stimulation of SGN
      should be controlled from 0.1 mA-0.4 mA. Acetylcholinesterase of the cochlea
      efferent nerve would increase with weak current stimulation (0.1 mA) which might
      play an important role in the protection of SGN during ototoxicity. This
      experimental results led to the conclusion that Na(+)-K(+)-ATPase of the SGN
      could be taken as an objective indicator presenting the functional changes of SGN
      quantitatively.

PMID- 7803100
TI  - [An experimental observation on the influence of the different levels of
      estradiol on the nasal mucosa].
AB  - The histomorphological influences of ovariectomies and estradiol injections on
      the nasal mucosa were observed in adult female guinea pigs. In the mucosa of
      ovariectomized guinea pigs, degenerative changes including dissolving and
      desquamation of cilia and glandular hypotrophy were found. On the contrary,
      thickening layer of the epithelium, spongiosis and edema of the corium,
      hyperplasia of glands and increased density of cilia were observed in the mucosa
      of guinea pigs receiving estrogen. The results demonstrated that different levels
      of estrogen might have different effects on the nasal mucosa.

PMID- 7803101
TI  - [The embryonic development of the ostiomeatal complex from 8 to 40 weeks].
AB  - The embryonic development of the ostiomeatal complex from 8-40 weeks was studied
      under the light microscope. From our observation, the uncinate process was
      visible on the laterosuperior portion of the inferior turbinate at 8 week's
      gestation. By 12 weeks, the ethmoid bulla was first identifiable on the lateral
      wall of the middle meatus. The primordial ethmoidal infundibulum and primordial
      maxillary sinus were seen developing lateral to the uncinate process in the
      middle meatus. The air cells of the middle turbinate may be normal development of
      the ethmoidal labyrinth. Congenital nasal septum deviation may cause malformation
      of the ostiomeatal complex.

PMID- 7803102
TI  - [Studies on the nasal absorption of gentamycin].
AB  - Study on drug absorptive function of nasal mucosa is a new and interesting
      subject bridging otorhinolaryngology and pharmacology. The authors applied 40
      mg/ml gentamycin to 10 dogs at the dose of 5 mg/kg through three routes of
      administration, ie, intravenous, intramuscular and intranasal. The serum levels
      of the drug from 0 to 180 minutes after applying the drug were determined with
      thin-layer chromatography-scanning method and the bioavailability of three routes
      was counted. It was found that within 10 to 30 minutes after using gentamycin the
      drug concentration in the blood increased and reached a peak. The half-life
      period was about three hours. The bioavailability of the intranasal
      administration were 80.5%, and intramuscular 42%. It was indicated that the nasal
      mucosa possessed an excellent penetrance for gentamycin and let it be absorbed
      into blood stream quickly and maintain an effective level for a long time.

PMID- 7803103
TI  - [Submucous implantation with pedicel auto-flap of cheek muscle for atrophic
      rhinitis].
AB  - This paper described a method of submucous implantation for 32 patients with
      atrophic rhinitis by using pedicel auto-flap of cheek muscle and maxillary
      periosteum of piriform aperture. The results indicated that the total effective
      rate was 100% and the evident effective rate was 90.6% after 1 to 3 year
      postoperatively. The cilia beat of nasal mucosa, blood flow, osmotaxis of blood
      vessel. P substance and the resistance of nasal airflow were all improved. The
      flap survived and grew well due to autogenuous graft tissues and its original
      blood supply. No complications have been found. The clinical efficiency was
      obvious for a short term and was stable for a long term.

PMID- 7803105
TI  - [Surgical anatomy of the lateral wall of the sphenoid sinus].
AB  - Sixty-three sphenoid sinuses were examined in cadavers, with special attention to
      the neural and vascular structures on the lateral wall of the sinus. There are
      three structures producing prominences on the lateral wall of the sinus, 1) The
      carotid artery, including its presellar segment, infrasellar segment and
      retrosellar segment. The means of length, thickness and the distance to the
      middle line of the presellar one are 6.8 mm, 1.0 mm and 6.2 mm respectively. The
      means lf length, thickness and the distance to the middle line of the infrasellar
      one are 6.6 mm, 1.0 mm and 5.0 mm respectively. The means of length, thickness
      and the distance to the middle line of the retrosellar one are 6.6 mm, 1.8 mm and
      7.1 mm respectively. 2) The bulge of optic canal, the means of its length,
      thickness and the distance to the middle line in sphenoid sinus are 4.8 mm, 1.0
      mm and 5.5 mm respectively. 3) The maxillary branches of the trigeminal nerve,
      the mean of its length, thickness and the distance to the middle line in sphenoid
      sinus are 5.3 mm, 1.2 mm and 8.5 mm respectively.

PMID- 7803104
TI  - [The diagnosis and treatment of sphenoid inflammatory neoplasms and sphenoid
      sinus tumors].
AB  - We have analyzed the clinical data of 27 cases of sphenoid inflammatory neoplasms
      and sphenoid sinus tumors including inflammations (12 cases), benign tumors (10
      cases) and malignant tumors (5 cases). The characteristics of sphenoid
      inflammatory neoplasms were compared with those of sphenoid sinus tumors. On CT
      scanning and magnetic resonance imaging (MRI) we found that sinusitis resulted in
      much less bony erosion than tumors on CT scanning and that the T2-signal
      intensity on MRI increased much more in sinusitis than in tumors. We have
      discussed the indications of various operative approaches and suggested that the
      approach of external ethmoidectomy is a method of choice.

PMID- 7803106
TI  - [Effect of hypoxia at 5% oxygen on global electrophysiological responses from
      normal awake guinea pigs].
AB  - All experiments were conducted on awake guinea pigs warranting a normal
      physiological function of the circulatory system. Global electrophysiological
      responses from the round window of cochlea were monitored: cochlear microphonic
      (CM), summating potential (SP) and auditory compound action potential (AP). The
      results showed that hypoxia induced a threshold elevation at all frequencies thus
      affecting the whole cochlea, and also very large diminutions of AP at high
      intensity level exclusively in response to a high frequency, and very large
      increases of SP at 2 kHz and 8 kHz. After hypoxia, which lasted thirty minutes, a
      considerable recovery occurred, and at the end of the session recovery reached
      around eighty percent. Alterations of cochlea action potential in response to
      high intensity stimuli were dissociated from threshold changes. We speculate that
      threshold elevation could be associated with over-all energetic (ATP) decrease
      leading to diminution of endolymphatic resting potential. Action potential
      changes at high intensity and at cochlear base could reflect neurotransmission
      (afferent, efferent or sympathetic) disturbance.

PMID- 7803107
TI  - [Effect of sexual hormones on proliferation of laryngeal carcinoma cell line HEp
      2 in vitro].
AB  - In this study, we observed the effect of FCS and DCC FCS on the proliferation of
      HEp-2 cell in vitro with dextran-coated charcoal technique, and explored the dose
      dependence of HEp-2 cell to testosterone, 17 beta-estradiol and progesterone. The
      results showed that HEp-2 cell line is androgen-sensitive cell, and testosterone
      at concentration of 1 nmol/L and 10 nmol/L may stimulate the proliferation of HEp
      2 cells, but 17 beta-estradiol and progesterone have no such effect. The results
      suggested that HEp-2 cell line is a proper model in vitro for the study of
      laryngeal carcinoma and sexual hormones. This study offered the evidences of the
      endocrine therapy for laryngeal carcinoma.

PMID- 7803108
TI  - [Experimental study on the reinnervation of the vocal cord adductor by
      implantation of ansa cervicalis].
AB  - The sub-branches of main branch of ansa cervicalis were cut and implanted into
      the thyroarytenoid and lateral cricoarytenoid muscles on the left side in 7 dogs
      after the recurrent and superior laryngeal nerves were sectioned on the same
      side. After six months, laryngoscopy showed that adduction of the vocal cord
      recovered in five post-operative cases. Adduction was caused by the reinnervated
      adductor muscles, as demonstrated by laryngeal electromyography, histologic
      studies, tension of contraction and electron microscopy for the neuro-muscular
      junctions. The present results demonstrated that the procedure seemed to produce
      satisfactory reinnervation of the adductor musculature.

PMID- 7803109
TI  - [Prognostic value of blink reflex in patients with Bell's palsy].
AB  - Blink reflex(BR) and electroneurography (ENoG) were carried out in 31 healthy
      people to obtain normal value. The manifestations of nerve excitability
      test(NET), ENoG and BR of 60 patients with Bell's palsy within 3 weeks of onset
      were studied. The results indicated that when the appearance of BR was regarded
      as good prognosis, facial paralysis recovered completely, the rate of accuracy of
      predicting facial paralysis was 100%, when the disappearance of BR was regarded
      as bad prognosis, it isn't a useful test for evaluating prognosis of facial
      paralysis within the first week of onset (for very few cases tested with NET and
      ENoG), and less useful than ENoG and NET within the second week and similar to
      ENoG and NET within the third week of onset.

PMID- 7803110
TI  - [Digital subtraction angiography in otorhinolaryngology--preliminary report].
AB  - The paper presents the preliminary experience with digital subtraction
      angiography (DSA) in otorhinolaryngology. This series included racemose
      hemangioma of the auricle in 3 cases, juvenile angiofibroma of nasopharynx in 4
      cases, angioma in the retropharyngeal space in 1 case, tympanic body tumor in 1
      case, traumatic epistaxis in 1 case, traumatic pseudoaneurysm in 1 case. The
      site, supply arteries, drainage veins of vascular tumors were shown with DSA. The
      intraoperative bleeding was reduced significantly by preoperative embolization of
      supply arteries to vascular tumors. The broken arteries of the traumatic
      epistaxis and the traumatic pseudoaneurysm were not only discovered but
      embolized. The indications and complications of DSA and measures for preventing
      and reducing complications were discussed.

PMID- 7803111
TI  - [Evaluation of postural sway in normals and patients with vertigoes].
AB  - A measurable parameter in the study of static equilibrium was described. The
      locus of postural sway was measured with a set of computer during 1 minute period
      in 68 normal subjects and 82 patients suffering from central and peripheral
      vertigoes with eyes closed. The results demonstrated: 1) There are five patterns
      of postural sway: centripetal, forward-backward, right-left, diffuse and
      multicentric patterns; centripetal pattern was the most prominent figure pattern
      in the normal subjects, diffuse pattern was the most prominent figure pattern in
      the central vertigoes. 2) Length of locus and velocity of postural sway of the
      patients were significantly increased in comparison with normal subjects. 3) The
      length of locus was the shortest and velocity of sway was the slowest in the 20
      year group. There was difference between 20- year and 10-year group (P < 0.05),
      the difference between 20-year and 50-year was more significant (P < 0.01).

PMID- 7803112
TI  - [Study on mechanism of eustachian tube active opening ventilation and pump-like
      function].
AB  - A modified methods for assessing the eustachian tube function (ETF) in patients
      with traumatic tympanic membrane perforation and otitis media were developed by
      using a custom-designed ETF measuring instrument. These methods consist of
      dynamic flow swallow test (DFST), positive pressure swallow test (PST), negative
      pressure swallow test (NST) and micro-negative pressure swallow test (MNST). With
      these methods, the graphs and parameters presenting ET active opening function
      were obtained. The results suggested that the ET active swallow opening is a
      rather complex process of biomechanical action. It is not only closely related to
      the function of middle ear ventilation but also related to pump-like function and
      the protective function against reflux infection from nasopharynx.

PMID- 7803113
TI  - [The uvulopalatopharyngoplasty operation for obstructive sleep apnea syndrome].
AB  - We performed uvulopalatopharyngoplasty operations on 216 patients and conducted 6
      month to 2-year follow-ups. 40 patients have had polysomnograms before and after
      operations. The clinical results showed 50 percent markedly improved, 28 percent
      somewhat improved, and 22 percent unimproved. The total success rate was 78%. The
      surgical procedures and polysomnogram methods have been introduced, and the
      pathogenesis, diagnostic criteria and results were discussed.

PMID- 7803114
TI  - [Synchronous analysis of multi-channel spectrum for human resonance cavity].
AB  - The synchronous analysis of multichannel spectrum were used to determine the
      regulars, conditions and characters of the resonance when subjects pronounced.
      140 subjects were selected for test and 1040 pieces of sound sample were
      collected, then the analysis of different parts (mouth, throat, head and chest)
      was done. The results of the analysis of variance showed that there was much
      difference among the various professional workers, different places of
      articulation, and patients with voice disorders in spectrum analysis (P < 0.001).
      Each part of resonance frequencies was put forward of pronouncing system. High
      frequency resonance comes from head and pharynx (above 2000 Hz high resonance
      cavity), and low frequency resonance comes from chest and larynx (less than 2000
      Hz resonance cavity). We suggest that there are six degrees of clinical objective
      classification of the pathologic hoarseness.

PMID- 7803115
TI  - [Analysis of misdiagnostic acoustic neuroma].
AB  - 72 cases (74 tumors) of acoustic neuroma pathologically confirmed after operation
      were analysed with special regard to the misdiagnosis made in their initial
      seeking for medical advice from ENT doctors. The average period of misdiagnosis
      was 5.48 years. The disease entities that the acoustic neuroma had been mistaken
      for were sensorineural hearing loss of unknown origin, idiopathic sudden
      deafness, tinnitus of unknown origin, cervical osteophytosis, nasopharyngeal
      carcinoma, etc. Emphasis was placed on the discussion of various causes of
      misdiagnosis.

PMID- 7803116
TI  - [Causes of erroneous diagnosis in SOM].
AB  - During the years of 1988-1990, 230 ears were diagnosed as secretory otitis media
      (SOM), with intact data, in which 23 ears failed to be diagnosed. Atypical
      symptom, carelessness in collection of history and in examining the tympanic
      membrane were considered as one of the important causes of erroneous diagnosis.
      Analysis of pure tone audiogram should be combined with the age and the former
      history of patients. "B" type tympanograph has 88% positive rate in diagnosing
      SOM. So in children, acoustic impedance should be used as a routine audiometric
      measurements, even if with clear history of receiving ototoxic drug.

PMID- 7803117
TI  - [Delayed cerebrovascular accident following microvascular decompression of
      hemifacial spasm].
AB  - Two cases of hemifacial spasm received microvascular decompression. Both of them
      had histories of hypertension and coronary insufficiency. The two cases died on
      the 12th postoperative day because of cerebrovascular accident. We think that the
      death was associated with the poor facilities, insufficient skills and lack of
      close supervision. Also, frequent visits by the families and early activities of
      the patients may contribute to the accident.

PMID- 7803118
TI  - [Bleeding and complications related to hemorrhage during transsphenoidal removal
      of pituitary tumor].
AB  - 450 cases who undertook the transsphenoidal removal of pituitary tumors from 1982
      to 1992 were reviewed. The bleeding during operation and the complications
      related to the bleeding were reported in 19 cases. The intercavernous sinuses
      were traumatized during operation in 9 cases. The possibility of abnormal dural
      arteries existed in 3 cases. The bleeding happened in the course of dissociation
      of nasal septum in 2 cases. The cause of bleeding in 3 cases were unclear. There
      was no much bleeding or bleeding record during operation, but postoperative
      bleeding complications appeared in other 2 cases. Heavy bleeding came from nose
      repeatedly in 2 cases, one of which was confirmed as pseudoaneurysm. The
      postoperative subarachnoid haemorrhage in 2 cases, one blindness and one
      paralysis of abductor nerve happened. The causes of bleeding and complication
      were discussed.

PMID- 7803119
TI  - [Arterial embolization leading to fatal cerebral infarction (a case report)].
AB  - A case of severe epistaxis with hypertension and arteriosclerosis was treated by
      embolizing the ipsilateral internal maxillary artery after routine methods of
      hemostasis had failed. Although epistaxis stopped after embolization, cerebral
      infarction, hemiplegia and deep coma developed, and the patient died on the ninth
      postoperative day. We conclude that superselective embolization of the branches
      of external carotid artery for treating severe epistaxis should be used with
      great caution or not be used in patients with arteriosclerosis.

PMID- 7803120
TI  - [Study on pathogenic mechanism of hemifacial spasm].
AB  - In 17 cats, areas of focal injury were induced in the facial nerve root near the
      brain stem by implantation of V-clamp and catgut suture. The electrophysiological
      examinations were made at 3 weeks after the surgery. When the mandibular branch
      of the facial nerve was electrically stimulated, a combined activity potential
      and a delayed activity could be recorded from the orbicular ocular branch of the
      facial nerve. The delayed activity disappeared after the motornucleu of the
      facial nerve was blocked with injection of 2% Lidocaine(1.5 microliter). These
      phenomena suggests that the artifacial synapses have been formed among the
      demyelinating facial nerve. The antidromic impulse of the mandibular branch of
      the facial nerve spread to adjacent fibers through the artifacial synapses in REZ
      of the facial nerve and causes the synkinases and spasm. Delayed activity may be
      caused by neurons of the motornucleu. Experimental lesion was also examined
      histologically at 3 weeks following implantation. Injured nerve showed areas of
      demyelination and Waller's degeneration of adjacent axons. The Nissle substances
      at the neurons of the motornucleu were dissolved and disappeared.

PMID- 7803121
TI  - [Experimental study on delayed reinnervation of vocal cord adductors].
AB  - The adductor branch was anastomosed with the main branch of ansa cervicalis to
      reinnervate the vocal cord adductors in six dogs at the time of denervation and
      after varying intervals of chronic denervation. Some recovery of adduction was
      noted within ten-month interval. Laryngeal electromyography, tension tests and
      histologic studies of the adductor muscles were correlated with the recovery of
      adduction. Although adduction didn't recover after twelve-month interval,
      striations of the adductor muscles were normal, only slight fibrosis was
      observed.

PMID- 7803122
TI  - [Facial nerve surgery with increasing innervation of correct target].
AB  - Aberrant regeneration of facial nerve has a higher propensity to innervate the
      wrong target. This study states that transection of these nonsomatic motor nerve
      will increase the innervation of correct target, which is cataloged as
      'transection group', and preservation of nonsomatic motor nerve as 'untransection
      group'. According to the House grading system for reporting recovery of the
      facial nerve, in incomplete lesions (Bell's palsy, Hunt's syndrome, trauma etc)
      treated with nerve total or subtotal decompression (101 cases), transection group
      produced better voluntary functional movement (average grade 1.66 +/- 0.74) than
      untransection group (average grade 2.81 +/- 0.87). In complete lesions (trauma,
      tumor and chemical destruction etc) treated with nerve grafting (65 cases),
      transection group obtained better improvement (average grade 2.63 +/- 0.73) than
      untransection group (average grade 3.65 +/- 0.78).

PMID- 7803123
TI  - [Chromosome 15 satellite enlargement and hereditary deafness].
AB  - The clinical and cytologic examinations in 6 deaf patients from 2 genealogical
      trees with chromosomal 15 satellite enlargement, karyotype 46, XY(X), PS++(15)
      are reported. A proband as well as his brother and sister suffered from phenotype
      with gradual hearing loss at the age of 12 to 13 and big satellite 15 existed in
      chromatinic karyotype. His father's phenotype was normal, but karyotype was the
      same as the 3 siblings of the proband, which suggested that the abnormal
      chromosome may originate from the father. The proband as well as his mother and
      uncle from family tree 2 may all suffer from dysaudia in both ears without any
      cause and with rapid exacerbation of the disease and deafness at last, 1 to 2
      years after birth. Based on the fact that they had similar clinical phenotype and
      karyotype, their delayed deaf-mutism may be related to the structural abnormality
      of chromosome 15. An examination of the proband's grandparents showed that both
      phenotype and karyotype were normal. The abnormal chromosome from the proband's
      mother and uncle may originate from a new mutation. Obviously, the proband's
      abnormal chromosome originates from the mother. It is estimated that such
      chromosomal structural abnormality may be caused by some hearing genetic effects.

PMID- 7803124
TI  - [Measuring of immune complexes and antinuclear antibodies in effusion of
      secretory otitis media].
AB  - Immune complexes (IC) and antinuclear antibodies (ANA) in middle ear effusions
      from 40 cases (45 ears) of secretory otitis media were measured using PEG
      precipitation method and fluorescent microscopy. The range of absorbence for IC
      varies between 0.124-0.512 in patients and is higher than those (0.132) in normal
      human sera. Thirty-two ears (71.1%) are ANA positive. The result indicates that
      secretory otitis media is related with autoimmunity. The deposit of IC may be one
      of the causes of effusion in otitis media.

PMID- 7803125
TI  - [Intranasal endoscopic management of cerebrospinal rhinorrhea].
AB  - The excellent visualization and atraumatic surgical techniques of endoscopic
      sinus surgery have been applied to the management of five cases of cerebrospinal
      rhinorrhea in the last 3 years. In all the cases, the exact sites of the lesion
      were identified on ethmoid roof (2 cases) or sphenoid sinus (3 cases). The
      procedures of the operation were as follows: to enlarge the leak and at the same
      time to block up it with the muscles, and then covering the muscles with fascia.
      All of the five cases were cured by one-step surgery. The techniques and
      indications for endoscopic management of cerebrospinal rhinorrhea are discussed.

PMID- 7803126
TI  - [Biological study on prognosis of laryngeal carcinoma with regional metastatic
      lymph nodes].
AB  - The purpose of this study is to find out the biological feature of laryngeal
      cancer and metastatic lymph nodes with DNA Image Analysis, Argyrophilic Nucleolar
      Organizer Region (AgNOR), Carcinoembryonic Antigen (EA) and Estrogen Receptor
      (ER) 30 patients were included in this study. It was found that carcinomatous
      tissues showed a statistically significantly higher DNA content, AgNOR content,
      and positive reaction of CEA and ER than those of normal tissue (P < 0.01).
      Paired comparisons were performed in primary tumor and metastases and didn't show
      statistical difference (P > 0.05). The group with survival time over 5 years had
      a significantly lower DNA content, AgNOR content, CEA positive reaction of
      metastases and higher ER positive reaction of metastases than those with less
      than 5 years survival (P < 0.01). But there no was consistant relationship
      between primary tumor CEA or ER positive reaction and survival time (P > 0.05).
      The patients who accepted radiotheraphy had better prognosis than those who
      didn't (P < 0.05). The above results indicate that the combined analysis of
      metastases and primary tumor will provide a good feature for biological activity.
      In addition, radiotherapy before and after operation will be beneficial.

PMID- 7803127
TI  - [Myoperiosteocutaneous flap repair of trachea wall defects].
AB  - The experience of repairing the defect of trachea wall by using the
      sternocleidomastoid myoperiosteal or pectoral myoperiosteocutaneous flaps in 7
      patients was reported. The operation was successful in all patients except one
      who complicated with local infection. The advantages and surgical technique were
      discussed in this paper. The periosteal flap with blood supplied muscle pedicle
      has good osteogenetic potency which is suitable to meet the specificity of
      tracheal repair. This method is simple, safe and reliable.

PMID- 7803128
TI  - [Carotid body tumor: diagnosis and surgical treatment].
AB  - Carotid body tumors are rarely encountered and can present a difficult surgical
      problem. During the period of June 1988 to November 1992, 8 patients were
      operated on for carotid body tumors at PLA General Hospital. Details of the
      surgery, morbidity and outcome of these patients are presented. Our experience
      suggests that: 1) The presence of a pulsatile neck mass located in the region of
      carotid triangle, vertically fixed and laterally mobile, should raise the
      suspicion of a carotid body tumor; 2) Color Doppler flow imaging has a role to
      play in the diagnosis of carotid body tumor; 3) DSA is very important for a
      number of reasons, especially for the use of concomitant embolization; 4)
      Management of these tumours is primarily surgical; 5) The decision whether to
      resect the carotid artery or not can only be made intra-operatively based on
      status of the patient and tumor, there might be 4 surgical options open to the
      operators.

PMID- 7803129
TI  - [Pathogenesis of perennial rhinitis].

PMID- 7803130
TI  - Selection of oligonucleotide probes and experimental conditions for multiplex
      hybridization experiments.
AB  - Different DNA probes hybridize under different conditions. I examine the
      constraints of the design of oligonucleotide probes that are meant to hybridize
      to different unique sites in human genomic DNA under a single set of
      hybridization conditions as a parallel array. In 522 kb of human genomic DNA, 75%
      of 12-base and 89% of 22-base are unique, as opposed to 90% and 100% as expected
      of unstructured DNA, and this is not due solely to repetitive elements in the
      DNA. Hybridization in TMAC to reduce A+T content effects on melting temperature
      allows only 90% of unique targets to be hybridized under one set of conditions if
      a 2 degrees C difference between matched and mismatched sequences is required.
      Standard hybridization conditions allow no more than 60% of unique probes to be
      used together. This suggests that probe, hybridization conditions, and instrument
      design for multiple-probe hybridization applications will be harder than
      previously suggested.

PMID- 7803131
TI  - Simple and robust screening of pooled yeast artificial chromosome libraries by
      the restriction enzyme digestion of polymerase chain reaction products.
AB  - The polymerase chain reaction (PCR)-based method for screening pooled yeast
      artificial chromosome (YAC) libraries was modified by adding a step for the
      restriction enzyme digestion of the PCR products. This modification significantly
      increased the reliability of YAC screening and made it possible to identify YAC
      clones without a cumbersome verification step by colony hybridization and/or
      Southern blotting. Using this method, we assigned 39 mouse YAC clones to a mouse
      genetic map with 13 biallelic, polymorphic expressed sequence tags. This method
      provides a fast, reliable way to identify YAC clones with PCR-based sequence
      tagged sites.

PMID- 7803132
TI  - Use of chromosome microdissection, the polymerase chain reaction, and dot blot
      hybridization to analyze double minute chromosomes.
AB  - The potential usefulness of chromosome microdissection, the polymerase chain
      reaction (PCR), and dot blot hybridization as a quick screening method for
      determining the genetic composition of double minute chromosomes (DMs) was
      evaluated. DMs or abnormally banding regions (ABRs) were microdissected from
      multidrug-resistant hamster cell lines and amplified with PCR using primers
      specific for the hamster multidrug-resistance (MDR) gene, pgp 1. The
      microdissected-PCR-amplified products were shown to (a) hybridize to a 32P
      labeled pCHP1 probe for the hamster MDR gene by using dot blot or Southern blot
      analysis and also (b) hybridize back to the chromosome region from which they
      were originally dissected by using fluorescent in situ hybridization.
      Microdissected/PCR-amplified DMs were also shown to hybridize to ABRs. When
      microdissected DMs and ABRs were amplified using hamster specific Alu primers,
      the resulting material was shown to hybridize with probes for hamster MDR and
      Alu. These results suggest that the DMs contained in these MDR hamster cell lines
      contain Alu-like sequences and the chromosome microdissection-PCR-hybridization
      approach might be used as a quick screening method for identifying genes
      amplified in DMs and ABRs in cell lines and human tumor samples.

PMID- 7803134
TI  - Genetic analysis: techniques and applications bibliography.

PMID- 7803133
TI  - Centromeric and telomeric repeats are stable in nonagenarians as revealed by the
      double hybridization fluorescent in situ technique.
AB  - We report a simple method for simultaneous identification of centromeric and
      telomeric repeat sequences of human chromosomes. Employing this technique, we
      investigated the stability of centromeres and telomeres in individuals over 90
      years of age and compared them with younger controls (< 40 years). Our findings
      suggest that centromeric and telomeric repeats remain apparently stable in
      nonagenarians. These findings are enigmatic because it has been suggested that
      centromeres are lost in older individuals. Furthermore, telomeric shortening has
      been observed in aged lymphocytes and cellular senescence. However, stability of
      telomeric repeats noted in nonagenarians may be masked by loss followed by
      compensation by a process called telomeric elongation.

PMID- 7803135
TI  - Guided bone regeneration for enhanced esthetics: edentulous ridge contours
      beneath pontics and hard tissue repair of postoperative ridge defects.

PMID- 7803136
TI  - Response of normal and tetracycline-stained teeth with pulp-size variation to
      nightguard vital bleaching.

PMID- 7803138
TI  - "Supra-dammed impressions": successful impressions with rubber dam in place.

PMID- 7803137
TI  - Esthetic alternative to conventional resin-bonded fixed partial dentures with In
      Ceram.

PMID- 7803139
TI  - Glass-ionomer restoratives and liners: shear bond strength to dentin.

PMID- 7803140
TI  - Dental infection control--can we call the changes progress?

PMID- 7803141
TI  - Multiple diastema management: an interdisciplinary approach.

PMID- 7803142
TI  - What is the future for dental specialists? Two sides of the coin.

PMID- 7803143
TI  - The Quayside convention for the clarification of confused molars.

PMID- 7803144
TI  - The TMD series.

PMID- 7803145
TI  - The TMD series.

PMID- 7803147
TI  - Restorative index.

PMID- 7803146
TI  - Poison in the mouth.

PMID- 7803148
TI  - An evaluation of training general dental practitioners in partial denture design
      using a computer-assisted learning program.
AB  - The authors of this paper produced a computer-assisted learning (CAL) program on
      aspects of partial denture design which covered the topics of surveying, support
      and indirect retention. Version 1 of the program was evaluated by 65 general
      dental practitioners, the majority of whom did this at their own homes or
      practices whilst the rest came in to the School of Dentistry. Participants were
      of varied ages and computer experience. A total of 85% of the participants found
      the program easy to use and 78% claimed the program had improved their knowledge
      of partial denture design, although less than half thought it had improved their
      practical skills. Opinions varied on which of the three topics were the most
      useful, and interest in future CAL material for dentistry was high. The study
      shows that CAL can be an acceptable, effective and enjoyable form of training for
      general dental practitioners who have access to modern microcomputers.

PMID- 7803150
TI  - The relationship between registration and dental health benefit in 8- and 9-year
      old children in Cheshire.
AB  - The dental treatment needs of 8- and 9-year-old children registered with a GDP
      for at least 6 months were compared with the dental treatment needs of children
      from a similar social background who were neither registered nor regularly
      attending the Community Dental Service. The children were examined by one of the
      authors without prior knowledge of registration status for evidence of treatment
      need. Unequivocal treatment need was defined as untreated dental caries in
      permanent teeth, sepsis associated with deciduous teeth, instanding maxillary
      incisors, and untreated permanent teeth fractured into dentine; untreated caries
      in the deciduous teeth was also recorded. Registration status of the children was
      subsequently obtained from the Dental Practice Board. Sixty-three per cent of the
      children had been registered with a GDP for at least 6 months at the time of the
      survey, 6% had been registered for less than 6 months and 31% had never been
      registered under the new dental contract. Of the children who had been registered
      for more than 6 months, 18.5% had unequivocal treatment need as against 17.5% in
      the unregistered group; 40.4% of the registered children had decay in their
      deciduous teeth, as against 36.5% of the unregistered children. Comparison of the
      dental treatment needs of registered and unregistered children showed no
      significant difference between the two groups.

PMID- 7803149
TI  - The evaluation of three computer-assisted learning packages for general dental
      practitioners.
AB  - Two studies were undertaken to determine the acceptability of computer-assisted
      learning (CAL) to general dental practitioners. The first was a single programme
      in two parts designed to give experience in orthodontic cases assessment and
      treatment planning, developed at the Bristol Dental School. The second contained
      two modules, one on the planning and management of dental biopsy and the other on
      surgical endodontics, developed within the Leeds Dental Institute. An identical
      self-administered questionnaire was completed by participants in the evaluation
      study. Knowledge and skill gains were indicated following study of the modules.
      The modules were also found to be easy to use and useful. The CAL approach was
      rated positively compared to audio tapes, books and journals, but a less
      consistent pictures when CAL was compared with videotapes. The study provides
      evidence for the acceptability and potential of the CAL approach to general
      dental practitioners.

PMID- 7803151
TI  - Oral contraceptives and antibiotics: important considerations for dental
      practice.
AB  - This paper considers the possible interactions between oral contraceptive pills
      and antibiotics, in the context of modern dental practice. A review of the
      literature on such interactions leads to the conclusion that current national
      guidelines on the use of alternative contraceptive measures during a course of
      broad spectrum antibiotics in women also using the oral contraceptive pill should
      be emphasised and encouraged as part of good clinical practice. A patient
      information leaflet may be considered as a useful way of presenting such advice
      to female patients.

PMID- 7803152
TI  - Murder and cover-up could explain the Florida dental AIDS mystery.
AB  - This article reconsiders the murder theory regarding the transmission of the
      human immunodeficiency virus (HIV) from Dr David J. Acer to at least six dental
      patients which was initially dismissed by American investigators from the Centers
      for Disease Control and Prevention (CDC) and Florida Health and Rehabilitative
      Service Department (HRS). In the light of withheld behavioural evidence from
      medical records, legal testimonies, and personal interviews obtained during the
      investigation, the information presented here strongly supports the conclusion
      that these transmissions were most likely intended by the dentist to execute a
      political and social vendetta.

PMID- 7803153
TI  - Sensorimotor integration: organization of premotor networks in 'lower'
      vertebrates. Proceedings of the European Conference on Comparative Neurobiology.
      April 14-16, 1994, Doorwerth, The Netherlands.

PMID- 7803154
TI  - Some remarks on alleged qualitative differences between anamniote and amniote
      nervous systems.
AB  - There are no 'lower' compared to 'higher' vertebrates (craniates) placed along a
      linear process of evolution. The different vertebrate/craniate groups evolved
      independently from a common ancestor, and during this evolution, increases in the
      complexity of nervous systems and of behaviour are as common as simplification
      (e.g., in myxinoids, lungfishes and amphibians). The organization of premotor
      networks is basically the same among tetrapods. Similar to the afferent sensory
      systems (e.g., the visual system), the premotor system--at least in the context
      of feeding and calling--is organized in a parallel fashion, with separate
      channels carrying different information to motor centres, which are the level of
      integration. A command neuron or command neuron ensemble system exists neither in
      anamniotes nor in amniotes. At feeding or calling, anamniotes exhibit no
      stereotyped behaviour or 'fixed action pattern' compared to the plastic behaviour
      of amniotes; differences are only quantitative. All vertebrates possess bulbar
      and spinal motor program modules, which can be controlled in a flexible way by
      descending pathways and reafferent circuits.

PMID- 7803155
TI  - Tectal activation of premotor and motor networks during feeding in salamanders.
AB  - In salamanders, three separate pathways, a crossed and two uncrossed ones, extend
      from the tectum mesencephali to the brain stem and spinal cord. These pathways
      arise from different types of tectal neurons; their dendrites arborize in
      different layers of retinal afferents and, thus, receive different types of
      retinal information. Collaterals of descending axons extend in regions, where
      motoneurons and interneurons related to prey capture are situated. The response
      properties of tectal neurons, interneurons and motoneurons related to prey
      capture were revealed by intracellular recording with subsequent dye (biocytin)
      injection. Most tectal neurons exhibit long latencies after optic-nerve
      stimulation, which indicates a complex processing of visual information inside
      the tectum. Our data show that no one-way connection exists between the tectum
      and motor nuclei; rather, these centres, together with a number of interneurons,
      exhibit a complex interaction during feeding.

PMID- 7803156
TI  - Synaptic relations of the trigeminal motoneurons in a frog (Rana esculenta).
AB  - The cobalt tracing technique was used to study synaptic relations of trigeminal
      motoneurons and the axon terminals of the mesencephalic trigeminal nucleus (Vmes)
      in a frog (Rana esculenta). Most of the small calibre Vmes terminals containing
      spherical synaptic vesicles occupied presynaptic position in axodendritic
      contacts. Axoaxonic contacts of Vmes boutons were exclusively found at the
      postsynaptic site. The synaptic coverage of the trigeminal motoneuron dendritic
      tree increased somatofugally along the dendrites. Monosynaptic contacts between
      the trigeminal motor and mesencephalic nuclei occur very rarely indicating that
      this type of activation does not play a significant role in the frog.

PMID- 7803157
TI  - Audio-motor interface in anurans.
AB  - Like males of many anuran species, fire-bellied toads (Bombina orientalis) call
      antiphonally, which demonstrates an auditory input into the call-generating
      network. Males produce their calls by an inspiratory airstream, which is
      generated exclusively by contraction of the muscles of the buccal cavity. The
      painted frog (Discoglossus pictus) possesses a combined inspiratory and
      expiratory call mechanism, and also uses only buccal muscles. These muscles are
      controlled by branchial motoneurons, which receive vocal premotor input mainly
      from the pretrigeminal nucleus. The interconnections between the auditory pathway
      and the vocal pathway were examined by neuroanatomical tracing and intracellular
      recording. Mesencephalic auditory nuclei, laminar and magnocellular nucleus of
      the torus semicircularis, and tegmental nuclei constitute strong descending
      efferents, which, in turn, form collaterals that terminate in vocal premotor
      nuclei. These findings imply fast audio-vocal interfacing, which is a
      prerequisite for the control of antiphonal calling.

PMID- 7803158
TI  - Organization of 'feeding circuits' in birds: pathways for the control of beak and
      head movements.
AB  - Two sensorimotor 'feeding' circuits and their descending projections are
      described in the mallard and compared to those in the pigeon. The
      tactile/trigeminal circuit consists of a pattern of reciprocal connections of the
      nucleus basalis with the overlying parts of the frontal neostriatum (Nf) and
      hyperstriatum ventrale (HV). The dorsal zone of Nf projects to the sensorimotor
      part of archistriatum, to the paleostriatum augmentatum (PA) and to the lateral
      lobus parolfactorius. A comparable pattern of visual connections has been found:
      the ectostriatum has reciprocal connections with the intermediate neostriatum
      (Ni) and HV. Here, too, Ni has projections to archistriatum and probably to PA.
      Archistriatum is the source of a large descending pathway with, among others,
      substantial projections to the parvocellular reticular formation of the brain
      stem. This provides a pathway for telencephalic control of premotor systems of
      jaw, tongue and neck muscles. The paleostriatal complex is the source of the ansa
      lenticularis with projections to the nucleus spiriformis lateralis and the
      nucleus tegmenti pedunculopontinus, both projecting to the deep tectum. This
      pathway may be important for the control of body position. In the mallard, it
      includes a substantial trigeminal component that has not been found in the
      pigeon.

PMID- 7803159
TI  - The reticular premotor neurons of the jaw muscle motor nuclei in the mallard
      (Anas platyrhynchos L.).
AB  - The trigeminal and facial motor nuclei in the mallard comprise several subnuclei
      which innervate tongue, jaw and other head muscles. The premotor cells of the
      subnuclei innervating jaw muscles are distributed in two longitudinal cell
      columns within the parvocellular reticular formation (RPc). The ventromedial part
      of RPc contains cells projecting to subnuclei innervating either jaw-closer
      muscles or jaw-opener muscles. In the dorsolateral part of RPc three subdivisions
      may be recognized: a rostral part which projects to two trigeminal subnuclei
      innervating jaw-closer muscles, an intermediate part which does not serve as
      premotor area for any of the jaw motor subnuclei and a caudal part of RPcdl which
      projects to the trigeminal and facial motor subnuclei innervating jaw-opener
      muscles. Exteroceptive information from mechanoreceptors in the beak reaches all
      three parts of RPCdl. Muscle spindles in jaw-closer muscles may influence the
      activity of premotor cells of jaw-opener muscles through their projection upon
      the caudal part of RPcdl.

PMID- 7803161
TI  - Comparative neuroanatomy: place, principles, practice and programme.
AB  - In this paper an outline is presented of the foundations of comparative
      neuroanatomy. The significance of topology (i.e. the geometry of distortion) for
      an accurate analysis of the kinds of morphological transformations to which
      central nervous systems are subjected is emphasized. The major tasks of
      comparative neuroanatomy are: (1) to sample the variation existing in the central
      nervous systems on the basis of an analysis of a multitude of carefully selected
      species; (2) to place the patterns of variation found, wherever possible, in an
      phylogenetic context; (3) to relate the morphological data and relations
      determined, to their putative biological (functional, behavioural) significance,
      and (4) to reflect on the question of which specific factors and processes might
      have caused the changes through which the brains of organisms have passed, and to
      develop explanatory scenarios.

PMID- 7803160
TI  - Location of premotor neurons of the motor nuclei innervating craniocervical
      muscles in the mallard (Anas platyrhynchos L.).
AB  - Reticular premotor neurons of craniocervical muscles in the duck were localized
      with the retrograde tracer HRP and the anterograde tracer WGA-HRP. In the
      reticular formation neck premotor neurons were found in the gigantocellular
      reticular nucleus and in the ventromedial part of the parvocellular reticular
      nucleus rostral to the obex, and caudal to the obex in the nucleus centralis
      ventralis of the medulla. Results were compared with premotor areas of jaw
      muscles. The ventromedial part of the parvocellular reticular formation contains
      neck as well as jaw premotor neurons. This area may serve as the neural substrate
      for the coordination of neck and jaw movements.

PMID- 7803162
TI  - Some notes on the organization of spinal and supraspinal premotor networks for
      locomotion.
AB  - In this introduction to the session 'Premotor networks for locomotion' the basic
      pattern of vertebrate locomotion, i.e. lateral undulation, and its underlying
      spinal circuitry will be discussed. Aspects of supraspinal networks for
      locomotion with emphasis on the initiation of axial movements in agnathans and
      anuran embryos will be briefly discussed. Finally, data on limb premotor networks
      in terrestrial vertebrates, particularly turtles, will be summarized.

PMID- 7803163
TI  - Sensorimotor integration in the lamprey locomotor system.
AB  - The locomotor movements of vertebrates are controlled by rhythm-generating
      networks in the spinal cord. These circuits are under modulatory influence from
      different sources, of both supraspinal, propriospinal and sensory origin. This
      paper reviews the neuronal mechanisms underlying swimming movements in the
      lamprey, the CNS of which provides a convenient model system for detailed
      investigations of the cellular bases for vertebrate locomotor behaviour, and
      which can be studied under in vitro conditions. The principal organization of the
      spinal, segmental network responsible for the generation of the rhythm, intrinsic
      membrane properties of importance for burst activity, as well as different
      mechanisms for modulation of the network activity including its sensory control,
      will be briefly described. The principles for coordination between segments
      during locomotion will also be shortly described.

PMID- 7803164
TI  - Longitudinal gradients in the spinal cord of Xenopus embryos and their possible
      role in coordination of swimming.
AB  - We consider the hypothesis that the normal rostrocaudal spread of motor activity
      during swimming in Xenopus embryos depends on a longitudinal, rostrocaudal
      gradient in synaptic drive received by the pattern generating neurons in the
      spinal cord. Anatomical evidence shows that there is a rostrocaudal gradient in
      excitatory and inhibitory premotor interneuron numbers. Intracellular recordings
      were therefore made from neurons at different longitudinal positions to seek
      direct evidence for a gradient in synaptic drive. The main finding was that
      during fictive swimming the amplitude of the tonic excitatory synaptic input and
      the mid-cycle inhibition declined in a rostrocaudal direction and caudal to the
      twelfth postotic segment inhibition was absent altogether. Experimental
      manipulation of the gradients by the caudal application of pharmacological agents
      lead to changes or even reversal of the normal direction of spread of motor
      activity. To test whether a gradient in synaptic drive could organize a
      rostrocaudal spread of activity we have used a 48 neuron, 12 segment model of the
      spinal pattern generating network. This has shown that the gradient hypothesis
      can provide a sufficient explanation for much of the embryo's motor coordination.
      A gradient in synaptic drive provides a flexible mechanism to control sequences
      of motor activity.

PMID- 7803165
TI  - Oscillatory membrane properties of spinal cord neurons that are active during
      fictive swimming in Rana temporaria embryos.
AB  - We have sought evidence for intrinsic oscillatory membrane properties in spinal
      cord neurons which participate in fictive locomotion in Rana temporaria embryos.
      In the presence of tetrodotoxin to synaptically isolate intracellularly recorded
      neurons, the bath application of N-methyl-d-aspartate (NMDA) depolarizes neurons
      by 20 to 30 mV. It does not, however, elicit continuous membrane potential
      oscillations, as have been found in homologous spinal neurons of the lamprey.
      However, addition of the neuromodulatory amine 5-HT to the bathing medium rapidly
      induces repetitive large scale (up to 40mV) oscillations in membrane potential.
      These oscillations depend upon the presence of magnesium ions and are abolished
      by the NMDA antagonist, APV. They do not occur when 5-HT is applied in the
      absence of NMDA. Expression of oscillatory membrane behaviour thus appears to
      rely upon an interaction between 5-HT and NMDA receptors. Neuroanatomical
      evidence shows that endogenous 5-HT-containing descending projections are present
      in the ventrolateral margins of the spinal cord at this stage in development and
      could therefore trigger these oscillations during normal motor behaviour.
      Preliminary pharmacological studies support the conclusion that activation of 5
      HT1a receptors is involved in the induction process.

PMID- 7803166
TI  - The organization of vestibulo-ocular and vestibulospinal projections in the
      chicken embryo.
AB  - The functional neuroanatomy of vestibulo-ocular and vestibulospinal projections
      has been studied in the chicken embryo as a step towards elucidating the
      developmental mechanisms that determine the connectivity patterns of the
      vestibular system. Retrograde and anterograde axonal tracing, neurotransmitter
      immunohistochemistry, and retrograde transport of radiolabelled neurotransmitters
      or neurotransmitter analogs demonstrate that vestibular neurons are clustered
      into functionally specific populations. Each of these has a characteristic
      positional domain, projection pathway, and site of termination. At early
      embryonic stages, the positional domains of the various populations are
      systematically correlated with segmental and longitudinal territories of
      differential gene expression in the hindbrain. The intimate link between position
      and phenotype at these stages suggests that the functional identity of vestibular
      neurons is determined, at least in part, by mechanisms associated with early
      pattern formation of the neural tube.

PMID- 7803168
TI  - Sensorimotor aspects of flight control in birds: specializations in the spinal
      cord.
AB  - Avian bipedal locomotion and flight suggest specializations in sensorimotor
      integration as compared to quadrupedal vertebrates. Specializations at the level
      of the spinal cord were studied with neuroanatomical tracing experiments in
      pigeons. Bird-specific connections were found in the exteroreceptive system
      (receptors associated with feathers) and in the proprioreceptive system
      (spinocerebellar pathways). These specializations seem to be related to flight
      control. Neurons of the marginal nuclei (accessory lobes) in the lumbosacral
      cord, which are unique to birds, have propriospinal connections mainly to the
      contralateral ventral cord. The functional role of these nuclei remains
      enigmatic.

PMID- 7803167
TI  - Development of specific populations of interneurons in the ventral horn of the
      embryonic chick lumbosacral spinal cord.
AB  - The development, morphological and neurochemical properties of specific
      populations of interneurons were investigated in the ventral horn of the
      embryonic and mature chick lumbosacral spinal cord by using pre- and post
      embedding immunocytochemical as well as anterograde axonal tracing techniques. We
      have identified and traced the morphological maturation of the following cell
      groups: (1) Neurons immunoreactive for calbindin-D 28k (CaB), a calcium-binding
      protein that has been reported to be a marker of certain subsets of excitatory
      spinal neurons. We have distinguished and traced the maturation of three CaB
      immunoreactive cell groups in the ventral horn; (2) Neurons immunoreactive for
      GABA and glycine, the two putative inhibitory amino acid neurotransmitters in the
      spinal cord; (3) Neurons within the nucleus marginalis, a cell group located in
      the ventrolateral aspect of the white matter in close proximity to the lateral
      motor column. The characteristic features of the development of these neurons are
      discussed and correlated with previous neuroanatomical and physiological studies
      concerning motor functions in the developing chick spinal cord.

PMID- 7803169
TI  - Energy metabolism in spinal motoneurons of the zebrafish.
AB  - Enzyme histochemical profiles of the energy metabolism in spinal motoneurons of
      fish, ranging in length from 18 mm to 53 mm, were investigated. Energy is used
      for ion pumps to maintain the resting membrane potential and for other processes
      of which transport and biosynthesis may be the most important. In this paper
      particular attention is paid to the impact of biosynthesis on the energy
      metabolism in motoneurons. As the innervation ratio of fish motoneurons increases
      dramatically during growth, we suppose that the formation and maintenance of
      functional connections with the target muscle accounts for the high level of the
      energy metabolism in motoneurons.

PMID- 7803171
TI  - The role of motor command feedback in electrosensory processing.
AB  - Sensory motor-coordination and the descending modulation of sensory perception
      can be particularly well studied in the mormyrid electrosensory lateral line lobe
      (ELL). In this first order sensory processing network, electroreceptive primary
      afferent input is integrated with a corollary discharge signal which modulates
      neuron excitability immediately after the generation of an electric organ
      discharge. Corollary discharge feedback to the electrosensory lobe allows the
      brain to distinguish between reafferent sensory input, generated by
      autostimulation of cutaneous electroreceptors (resulting from the fish's own
      electric discharge) and exafferent sensory input, evoked by stimulation of the
      same cutaneous electroreceptors by an external electric source. Mechanisms of
      this type define the context of incoming sensory information and are the first
      step in the dynamic regulation of perception. The corollary discharge pathway
      originates from a collateral branch of the electromotor command neuron axons. It
      is relayed via bulbar and mesencephalic command-associated nuclei and reaches the
      ELL by way of projections from the cerebellar posterior granular eminence to the
      superficial layer of the ELL, and from juxtalobar and juxtalemniscal nuclei to
      the deeper layers of ELL. ELL is a geometrically organized laminar structure
      containing a variety of cell types. A number of them combine a spiny dendritic
      tree in the superficial molecular layer with non-spiny basal dendrites in
      plexiform or deeper layers. Sensory input may reach the basal dendrites of these
      neurons either directly or indirectly, via granule cells in the deeper layers of
      ELL, on which the primary afferent fibers terminate. All neurons recorded
      intracellularly in the ELL show strong interaction between electrosensory and
      corollary discharge input. Corollary discharge gating of sensory processing is
      plastic and depends on dynamic sensory-motor association.

PMID- 7803170
TI  - Comparative anatomy of cranial nerve motor nuclei: with a comment on evolution of
      the craniofacial region.
AB  - Changes of cranial nerve nuclei are investigated at three crucial points of
      phylogenesis in frogs, lizards and rats. Profound changes can be observed in the
      trigeminal and facial motor nuclei parallel to transformation of the primary
      mandibular joint into the secondary mandibular joint. New muscles appear for
      mastication and facial expression and they are innervated by new types of
      neurons. The muscular tongue appears first in tetrapods coinciding with
      terrestrial life. It can be shown that an entirely new type of neuron develops at
      the medullospinal junction for the innervation of the intrinsic tongue muscles.
      These muscles and their neurons are not homologous to somatic muscles and spinal
      cord neurons. The external eye muscles and their innervation are present from the
      early craniates through apes in virtually the same pattern of organization. They
      evolved coincidently with the head and are not homologous to any other
      structures. It is concluded that if we accept the 'neogenesis' view in head
      evolution, all contradictions imposed, by the 'segment theory', upon the
      interpretation and classification of cranial nerve nuclei can be circumvented.

PMID- 7803172
TI  - The teleostean torus longitudinalis: a short review on its structure,
      histochemistry, connectivity, possible function and phylogeny.
AB  - The older idea that the torus longitudinalis (TL) is part of the ascending
      cerebellotectal circuitry involved in control of eye movements is at odds with
      facts on the histological, hodological and physiological level. Instead of an
      input from the valvula cerebelli, the TL and the cerebellum both receive a
      collateral mossy fiber input from the same source (nucleus lateralis valvulae,
      dorsal tegmental nucleus). The new hodological information is more consistent
      with fine histological and physiological data and suggests that the TL is a link
      in premotor circuitry descending from telencephalon to brain stem.

PMID- 7803173
TI  - Functional organization of the reticulospinal system in teleosts.
AB  - We have investigated whether separate supraspinal systems exist that mediate
      overruling, local modulation, initiation and termination of the spinal network
      for locomotion. We show that the overruling and modulating systems lie
      intermingled in the brainstem, but can be separated by several criteria.
      Initiation and termination probably relate to one system which is functionally
      and anatomically separable from the overruling and modulating systems.

PMID- 7803174
TI  - Topography and fine structure of proprioceptors in the hagfish, Myxine glutinosa.
AB  - Topography and ultrastructural organization of proprioceptors in the striated
      parietal muscle of the hagfish, Myxine glutinosa, are described. Due to the
      topographical location of the afferent nerve terminals four subtypes of
      proprioceptors are distinguished. Type 1-receptor and type 2-receptor are
      localized in an encapsulated and lamellated corpuscular organ located along and
      above the myosepta of the parietal muscle. Type 3-receptor is composed of a
      complex of free en plaque nerve endings within the dense collagen fibre texture
      at the site where myoseptum, muscle fascia and body fascia fuse to a raphe. Type
      4-receptor resembles type 3 but it is localized in the straight collagen fibre
      bundles of the myoseptum and the body fascia. A proprioceptive function of the
      nerve terminals is discussed.

PMID- 7803175
TI  - Observations on the development of the lateral line system in the Pacific hagfish
      (Eptatretus stouti, Myxinoidea).
AB  - We investigated the development of the lateral line system of the Pacific
      hagfish, Eptatretus stouti, using three-dimensional reconstructions from serial
      sections. Adult hagfishes possess a number of densely innervated skin grooves of
      unknown function, and these grooves do not contain typical lateral line receptors
      (i.e. neuromasts). However, three separate lateral line placodes appear to be
      present during development and these placodes give rise to groups of neuromast
      primordia. Unlike in other craniates, the neuromast primordia do not develop into
      neuromasts, but they apparently transform into the skin grooves of adults.

PMID- 7803176
TI  - Sensory activity in the telencephalon of the clawed toad, Xenopus laevis.
AB  - In this study data are presented providing evidence that the striatum of the
      clawed toad, Xenopus laevis, processes mechanosensory, acoustic, and visual
      information and that multisensory interaction takes place in this telencephalic
      structure. Multimodal processing as well as the considerable effects of stimulus
      repetition rate on response amplitudes are in line with the finding that the
      striatum of Xenopus mediates attentional processes (Traub & Elepfandt, 1990).
      Further physiological studies are needed to delineate the functional organization
      of the striatum in amphibians.

PMID- 7803177
TI  - The use of tracers in explants of the developing reticular formation and spinal
      cord of Xenopus laevis.
AB  - The development of reticulospinal projections to the lumbar spinal cord is
      studied by using a collagen co-culture system. Outgrowing reticulospinal fibers
      seem to grow out in a straightforward direction, without a specific preference
      for the lumbar or tail spinal cord. Carbocyanine tracers such as DiI, DiO and DiA
      are used to label the outgrowing fibers or their parent cell bodies. In double
      labeling studies contacts of outgrowing reticulospinal fibers with lumbar
      motoneurons are analyzed. The advances of a confocal laser scanning microscope
      for such studies are illustrated.

PMID- 7803178
TI  - On the basal ganglia of amphibians: dopaminergic mesostriatal projections.
AB  - Recent studies have revealed a rather dense dopaminergic innervation of basal
      forebrain areas in anurans and urodeles. The aim of the present study is not only
      to extend these observations to the third order of amphibians, i.e. the
      Gymnophiona, but also to determine the cells of origin of the dopaminergic
      projection to the basal forebrain by means of combined tract-tracing/transmitter
      immunohistochemical techniques. Immunohistochemistry with antibodies against
      tyrosine hydroxylase (TH) and dopamine (DA) demonstrated some remarkable
      differences in the distribution of DA fibers within the basal forebrain. Whereas
      in anurans the nucleus accumbens receives a major DA input, in urodeles the DA
      input to the striatum prevails. In gymnophionans, both basal forebrain structures
      receive an equally dense DA innervation. The double-labeling studies revealed
      also differences in the distribution of the cells of origin of the DA striatal
      input. Although in anurans and urodeles DA cells in both the posterior tubercle
      and the midbrain tegmentum contribute to this projection, the mesostriatal
      projection of urodeles is more elaborated than that of anurans.

PMID- 7803179
TI  - Are rostral and caudal parts of the hippocampus of the lizard Gekko gecko related
      to different types of behaviour?
AB  - Spatial orientation is an important function of the hippocampus. In reptiles the
      medial cortex is the equivalent of the mammalian hippocampus. In this study we
      compared the structure and connections of the hippocampus of ground-dwelling
      lizards with those of gekkonid lizards which are able to walk on vertical walls
      as well as on the ceiling. This last type of locomotor behaviour makes high
      demands on spatial orientation. It appeared that, in contrast to the ground
      dwelling lizards, in geckos the small-celled part of the medial cortex can be
      divided into a rostral and a caudal part. The rostral part receives visual,
      auditory, vestibular and proprioceptive information from the dorsolateral
      thalamic nucleus. The caudal part is connected with the lateral cortex which is
      the recipient of olfactory information from the main olfactory bulb. Also the
      efferent connections of the rostral and caudal part of the small-celled part of
      the medial cortex to the septum, and via the septum to the preoptic and
      hypothalamic areas remain strictly separated. Since different behavioural aspects
      are localized in different preoptic and hypothalamic subdivisions it seems likely
      that the two parts of the hippocampus in gekkonid lizards serve different
      behavioural functions.

PMID- 7803180
TI  - Microcircuitry of the mormyrid electrosensory lateral line lobe.
AB  - The mormyrid electrosensory lateral line lobe (ELL) is a laminated structure in
      the dorsal rhombencephalon receiving topographically ordered primary sensory
      input from electroreceptors and corollary signals from the electromotor command
      nucleus. The structural basis of the integration of these and other inputs was
      investigated at the light and electron microscopical level using neuroanatomical
      tracers, immunohistochemistry and Golgi-impregnations. The ELL contains at least
      14 distinct cell types. These include small granule cells receiving primary
      afferent input, GABA-ergic spiny interneurons and glutamatergic projection
      neurons integrating sensory input and descending feedback, and deep intrazonal
      neurons. Present knowledge of the synaptic organization of the ELL afferents and
      cell types allows for a preliminary scheme of its microcircuitry.

PMID- 7803181
TI  - Primary afferents and second order projections of the trigeminal system in a frog
      (Rana ridibunda).
AB  - The trigeminal primary afferents and the projections from the sensory trigeminal
      nuclei were studied in a frog (Rana ridibunda) by means of tract-tracing
      techniques. Primary fibers from separate ophthalmic, maxillary and mandibular
      trigeminal branches form short ascending and long descending tracts. Ascending
      fibers innervate the principal trigeminal nucleus, a field just dorsal to the
      trigeminal motor nucleus, and the supratrigeminal nucleus. Descending fibers
      terminate separately in the descending trigeminal nucleus, depending on their
      branch of origin. Other primary targets are the rhombencephalic reticular nuclei,
      the ventral and caudal octaval nuclei, the nucleus of the solitary tract and the
      spinal cord. Ipsilateral intranuclear connections are accompanied by
      extratrigeminal projections that reach, among others, the thalamus, the
      mesencephalic tectum and the cerebellum. It is concluded that many amniotic
      features are shared by the anuran trigeminal system.

PMID- 7803182
TI  - Electrical coupling and intrinsic neuronal oscillations in Rana temporaria spinal
      cord.
AB  - In the presence of TTX and NMDA, spinal cord neurons in Rana temporaria embryos
      generate membrane potential oscillations, but only when 5-HT is added to the
      perfusate. These oscillations are voltage-dependent due to magnesium block of the
      NMDA receptor ionophore and can vary in amplitude between 0 and 40 mV with
      imposed membrane polarization. In contrast, the intrinsic frequency of the
      oscillations is unaffected by changes in membrane potential. This could result
      from electrical coupling amongst homonymous motoneurons. Here we present initial
      evidence for such connections and discuss their implications for the segmental
      control of rhythmic motor behaviour.

PMID- 7803183
TI  - Sensorimotor integration in the brain of reptiles.
AB  - Visual, auditory, and somatosensory information is, via several thalamic nuclei,
      relayed to the reptilian forebrain. These thalamotelencephalic projections
      terminate primarily in the dorsal ventricular ridge in a non-overlapping way.
      Subsequent parallel processing of the three sensory modalities throughout the
      DVR, striatum and globus pallidus resembles the fundamentally parallel form of
      organization in the mammalian basal ganglia. The lack of direct projections to
      the thalamus and the absence of extensive, intrinsic connections make a
      comparison of the dorsal ventricular ridge with the mammalian neocortex highly
      questionable.

PMID- 7803184
TI  - Plasticity in vestibular and spinal circuits after hemilabyrinthectomy in the
      frog.
AB  - Removal of the labyrinthine organs on one side results in static and dynamic
      disturbances. Some functional recovery is seen in frogs over time.
      Electrophysiological studies of the isolated brainstem and/or spinal cord of
      hemilabyrinthectomized frogs demonstrate changes in vestibular and spinal
      circuits. Comparison of the time courses of these changes with the known time
      course of postural recovery excludes changes in the vestibular nuclei as an
      explanation for the initial postural recovery process. Selective labyrinthine
      lesion suggest a causal link between utricular lesion, postural deficit, spinal
      plasticity and postural normalization.

PMID- 7803185
TI  - Central control of melanotrope cells of Xenopus laevis.
AB  - Our research focusses on the role of brain and hypophysis in the control of
      background adaptation in the clawed toad, Xenopus laevis. This adaptation is
      regulated by alpha-melanophorestimulating hormone (alpha-MSH). Previously, it was
      shown that various neurotransmitters influence alpha-MSH release. Here we report
      about the origin of these factors. Using retrograde labelling techniques combined
      with immunocytochemistry, it was found that the inhibitory transmitters dopamine
      and neuropeptide Y coexist in neurons in the suprachiasmatic nucleus. These
      neurons project to the pars intermedia and synaptically contact the alpha-MSH
      producing melanotrope cells. In the synapses also GABA is present. Tracing of the
      optic nerve indicated the presence of a direct retinosuprachiasmatic tract.
      Furthermore, locus coeruleus neurons project to the pars intermedia. They contain
      the inhibitory transmitter noradrenaline. The stimulatory factors corticotropin
      releasing hormone and thyrotropin stimulating hormone originate from the
      magnocellular nucleus which send its processes to the neural lobe of the
      hypophysis.

PMID- 7803186
TI  - Depth perception in salamanders: the wiring of visual maps.
AB  - Most members of the salamander family Plethodontidae exhibit fast and precise
      prey localization and are likely to use stereopsis for this task. Tectal and
      isthmic neurons were stained iontophoretically with biocytin after intracellular
      recording in order to investigate the fine structure and arborization pattern of
      dendritic and telodendritic trees. The back-projection of isthmic neurons to both
      tectal hemispheres exhibits a conspicuous and spatially restricted connection
      with tectal neurons and the afferent fiber layers, which probably plays an
      important role in the context of stereoscopic depth perception and detection of
      retinal disparities.

PMID- 7803187
TI  - Optimizing immunohistochemistry in diagnostic tumor pathology with antigen
      retrieval.

PMID- 7803188
TI  - Future perspectives in microwave applications in life sciences.

PMID- 7803189
TI  - Long-term follow up of patients with common variable immunodeficiency treated
      with intravenous immunoglobulin: reevaluation of intravenous immunoglobulin
      replacement therapy. IVIG therapy in CVID.
AB  - Five patients with common variable immunodeficiency treated in our hospital
      between December 1979 and December 1990 were given six kinds of intravenous
      immunoglobulin preparations (pepsin treated, S-sulfonated, polyethylene glycol
      treated, pH4 treated, alkylated, and pH4.25 formulation preparation) for
      replacement therapy. Duration of the therapy ranged from 7.6 to 11 years.
      Incidences of fever and acute infections were variable among patients, but no
      significant differences were seen in the incidences among periods given each
      preparation. Three cases revealed abnormal pulmonary functions in tests. Adverse
      reactions were rarely seen in our study periods, and no severe reactions were
      observed. No significant differences were seen in incidences of adverse
      reactions. Postinfusion levels of serum complement slightly decreased from
      preinfusion levels. However, the decrease in complement was not related to any
      adverse reaction. No long-term complications such as transmission of hepatitis
      have been observed. Our data suggest that no obvious differences exist between
      the efficacy and safety of each IVIG preparation. Differences of efficacy of IVIG
      replacement therapy may be due to the variable pathophysiology of each patient.

PMID- 7803190
TI  - Pentoxifylline enhances sensitivity of a human ovarian cancer cell line (OVC-8)
      to TNF-alpha.
AB  - The OVC-8 human ovarian cancer cell line constitutively expresses tumor necrosis
      factor alpha (TNF-alpha) mRNA and protein and is resistant to TNF-alpha. When OVC
      8 cells are treated with pentoxifylline (PTX), the level of mRNA for TNF-alpha is
      markedly reduced. Combination treatment of OVC-8 cells with PTX and TNF-alpha
      overcomes the resistance. PTX-treatment has no effect on the expression of TNF
      alpha mRNA in C30 cells, which do not constitutively express TNF-alpha mRNA. The
      combination of PTX and TNF-alpha do not overcome the resistance of C30 cells to
      TNF-alpha. PTX or anti-TNF-alpha monoclonal antibody has no effect on the growth
      of OVC-8 cells, suggesting that the growth of OVC-8 cells does not depend upon an
      autocrine action of TNF-alpha. The synergistic cytotoxic effect obtained with
      ovarian cancer cells suggests that the combination of PTX and TNF-alpha could be
      applied clinically in the therapy of TNF-alpha-producing ovarian cancer.

PMID- 7803191
TI  - Enhancement of interferon-beta production with sphingomyelin from fermented milk.
AB  - A fermented milk, Kefir, contains an active substance which enhances IFN-beta
      secretion of a human osteosarcoma line MG-63 treated with a chemical inducer,
      poly I: poly C. The active substance in the fermented milk was identified to be
      sphingomyelin (SpM) by a combined use of a fast atom bombardment mass
      spectrometry (FAB-MS) and a fast atom bombardment tandem mass spectrometry (FAB
      MS/MS). SpM from fermented milk (F-SpM) was a mixture of four molecular species
      of SpMs having C21-, C22-, C23- and C24-fatty acids. F-SpM enhanced the IFN
      secretion 14 times, SpMs from other sources also enhanced moderately (2-3 times).
      Sphingosine and lysosphingomyelin also enhanced the activity but ceramide and
      cerebroside did not.

PMID- 7803192
TI  - Suppression of cytokine production by supernatants from CD8+ lymphocytes
      activated by mycobacterial fractions: the role of interleukins 4 and 6.
AB  - Supernatants derived from CD8+ lymphocytes treated with mycobacterial components,
      or the partially purified carbohydrates from these supernatants, increased the
      production of IL-4 and IL-6 by mononuclear cells. The addition of anti-IL4 or
      anti-IL6 antibodies to LPS stimulated MN cells incubated with supernatants from
      CD8+ lymphocytes or carbohydrates resulted in the restoration of other cytokine
      production by these MN cells. Recombinant IL-4 and IL-6 on their own suppressed
      the production of IL-1 beta, TNF-alpha, IL-2 and IFN-gamma by mononuclear cells.
      Such suppression could be reversed with antibodies to IL-4 and IL-6. The addition
      of rIL-4 and rIL-6 did not increase the suppression of cytokine production
      induced by suppressor supernatants or carbohydrates. Interleukin 4 decreased the
      production of IL-6 by MN cells; whilst IL-6 suppressed IL-4 production in a dose
      dependent manner. Both effects could be reversed with the appropriate antisera.
      Our results suggest that mycobacteria could evade host immunity by inducing the
      production of IL-4 and IL-6 by host mononuclear cells. These cytokines, in turn,
      would suppress the production of other cytokines necessary for effective cellular
      immunity.

PMID- 7803193
TI  - A recombinant human interleukin-1 beta protects adriamycin-induced toxicity.
      Adriamycin cardiotoxicity and interleukin-1.
AB  - Pretreatment with recombinant human interleukin-1 beta (IL-1) protected normal
      BALB/c mice from the lethal effect adriamycin (ADM) of related to dose and
      frequency of administration. Posttreatment with IL-1 failed to protect.
      Neutrophil and platelet counts after the administration of ADM (16 mg/kg) did not
      differ between the group with and that without IL-1 pretreatment, whereas lipid
      peroxide levels in the heart were reduced in the group pretreated with IL-1. It
      appears that the chemoprotection mechanism of IL-1 lies in the prevention of
      cardiotoxicity due to ADM-induced free radicals.

PMID- 7803194
TI  - Studies on the biological effects of ozone: 5. Evaluation of immunological
      parameters and tolerability in normal volunteers receiving ambulatory
      autohaemotherapy.
AB  - Autohaemotherapy, after a bland treatment ex vivo of blood with ozone, is a
      fairly unknown medical procedure claimed to have therapeutic value in viral
      diseases and neoplasms. Having already shown that ozone acts as a mild inducer of
      cytokines, we have undertaken an investigation in normal rabbits and in normal
      volunteers aiming to evaluate eventual changes of some cytokine levels in plasma
      as well as of immunological parameters such as the Mx protein, neopterin, beta 2
      microglobulin and of some acute-phase proteins after single or repeated
      autohaemotherapy. We have also evaluated the potential development of of side
      effects. This study is the first one to show that autohaemotherapy can activate
      an immunological marker in normal subjects without procuring any toxic effects.

PMID- 7803195
TI  - Sequential immunotherapy using interleukin-1 followed by interleukin-2 of ascitic
      MOPC104E-bearing mice.
AB  - This study shows that intraperitoneal injection of interleukin-1 (IL-1), followed
      by interleukin-2 (IL-2), can effectively eradicate murine ascitic tumor cells.
      This antitumor effect of IL-1 and IL-2 was abolished when administration of IL-2
      preceded that of IL-1. Solid tumors inoculated subcutaneously (s.c.) into the
      back of mice were also sensitive to this combined i.p. therapy, indicating a
      systemically-operating antitumor mechanism. Splenocytes from tumor-bearing mice
      treated with IL-1 followed by IL-2 showed a strong tumor-neutralizing activity.
      The population responsible proved to be Lyt2.2 (CD8)-positive cells.

PMID- 7803196
TI  - Multivariate statistical brain electromagnetic mapping.
AB  - Brain Electromagnetic Topography (BET) has attained widespread use. The
      representation of EEG or MEG parameters as scalp maps (BETm) aids its clinical
      interpretation. However, some critical issues limit the usefulness of BETm. In
      particular, the conventional statistical assessment of BETm with respect to
      normative data is based upon marginal significance probability scales which
      involve multiple univariate comparisons (one at each recording site). As a
      consequence, the probability of false positive findings (type I error) is
      increased above its nominal level. The use of conservative levels avoids this
      phenomenon but results in a considerable increase of the probability of not
      detecting real abnormality (type II error). Furthermore, BETm are constructed
      without taking into consideration the patterns of correlations characteristic of
      electromagnetic data under normal states of brain functioning. This limits the
      capability of BETm of representing multivariate aspects of abnormality. This
      paper introduces some techniques to approach these difficulties. Multivariate
      Brain Electromagnetic Topographic maps (MBETm) are defined, which retain the
      attractive features of mapping but also take advantage of multivariate
      characteristics (in the spatial and frequency domains) to highlight aspects of
      neuropathology. Moreover, simultaneous significance probability (SSP) scales,
      valid for both BETm and MBETm, are introduced for the global control of the
      probability of a type I error. The use of these techniques is illustrated with
      data from patients with cortical tumours and with epilepsy. ROC analysis shows
      that in some cases there is a significant improvement in both detection and
      localization accuracy.

PMID- 7803197
TI  - Model misspecification detection by means of multiple generator errors, using the
      observed potential map.
AB  - Due to model misspecification, currently-used Dipole Source Localization (DSL)
      methods may contain Multiple-Generator Errors (MulGenErrs) when fitting
      simultaneously-active dipoles. The size of the MulGenErr is a function of both
      the model used, and the dipole parameters, including the dipoles' waveforms (time
      varying magnitudes). For a given fitting model, by examining the variation of the
      MulGenErrs (or the fit parameters) under different waveforms for the same
      generating-dipoles, the accuracy of the fitting model for this set of dipoles can
      be determined. This method of testing model misspecification can be applied to
      evoked potential maps even when the parameters of the generating-dipoles are
      unknown. The dipole parameters fitted in a model should only be accepted if the
      model can be shown to be sufficiently accurate.

PMID- 7803198
TI  - Significance probability mapping: the final touch in t-statistic mapping.
AB  - Significance Probability Mapping (SPM), based on Student's t-statistic, is widely
      used for comparing mean brain topography maps of two groups. The map resulting
      from this process represents the distribution of t-values over the entire scalp.
      However, t-values by themselves cannot reveal whether or not group differences
      are significant. Significance levels associated with a few t-values are therefore
      commonly indicated on map legends to give the reader an idea of the significance
      levels of t-values. Nevertheless, a precise significance level topography cannot
      be achieved with these few significance values. We introduce a new kind of map
      which directly displays significance level topography in order to relieve the
      reader from converting multiple t-values to their corresponding significance
      probabilities, and to obtain a good quantification and a better localization of
      regions with significant differences between groups. As an illustration of this
      type of map, we present a comparison of EEG activity in Alzheimer's patients and
      age-matched control subjects for both wakefulness and REM sleep.

PMID- 7803200
TI  - Three dimensional representation of brain electrical activity.
AB  - Brain topography mapping is a useful technique for the representation of
      electrical activity recorded on the scalp. It clarifies spatial and temporal
      relationships between different cortical areas. In this work we propose a system
      which includes several enhancements over those previously proposed, such as an
      optimised interpolation method and a three dimensional reconstruction of maps.
      This system is available in a personal computer environment. Results clearly show
      a superiority of the 3D representation over 2D maps obtained with different
      projections. The performance of this system in terms of speed and precision is
      comparable to that of dedicated image processing and image synthesis workstations
      proposed for brain mapping.

PMID- 7803199
TI  - Sources of attention-sensitive visual event-related potentials.
AB  - In a study of the neural processes that mediate visual attention in humans, 32
      channel recordings of event-related potentials were obtained from 14 normal
      subjects while they performed a spatial attention task. The generator locations
      of the early C1, P1, and N1 components of the visual evoked response were
      estimated by means of topographic maps of voltage and current source density in
      conjunction with dipole modelling. The topography of the C1 component (ca. 85 ms
      post-stimulus) was consistent with a generator in striate cortex, and this
      component was unaffected by attention. In contrast, the P1 and N1 components (ca.
      95 and 170 ms) exhibited current density foci at scalp sites overlying lateral
      extrastriate cortex and were larger for attended stimuli than for unattended
      stimuli. The voltage topographies in the 75-175 ms latency range were modeled
      with a 5-dipole configuration consisting of a single striate dipole and left
      right pairs of dipoles located in lateral extrastriate and inferior occipito
      temporal areas. This model was found to account for the voltage topographies
      produced by both attended and unattended stimuli with low residual variance.
      These results support the proposal that visual-spatial attention modulates neural
      activity in extrastriate visual cortex but does not affect the initial evoked
      response in striate cortex.

PMID- 7803201
TI  - Somatosensory evoked response source localization using actual cortical surface
      as the spatial constraint.
AB  - We localized right median nerve somatosensory evoked responses in a normal human
      subject using an equivalent dipole method applied to magnetic field recordings.
      High resolution, 3-dimensional MRI data were used to confine source locations to
      the cortical surface. Results localized in Brodmann area 3b corresponding to
      location of hand somatosensory cortex derived from direct brain stimulation
      studies. The solution was unique and total computational time for an exhaustive,
      brute-force search was small and the results realistic due to applied anatomical
      constraints. This study demonstrates feasibility of accurate, non-invasive,
      realistic localization of dynamic human cortical function using spatial
      constraints provided by MRI images.

PMID- 7803203
TI  - Proceedings of the 2nd Pan Pacific Conference. Sydney, Australia, February 10-12,
      1994. Abstracts.

PMID- 7803202
TI  - A spatiotemporal dipole model of the stimulus preceding negativity (SPN) prior to
      feedback stimuli.
AB  - Ten subjects performed a time production task, in which they were instructed to
      press a button four seconds after the presentation of an auditory stimulus. Two
      seconds after the button press they received either auditory or visual feedback
      on the temporal accuracy of their response. In such a paradigm negative slow
      brain potentials can be recorded preceding the response (Movement Preceding
      Negativity, MPN) as well as preceding the feedback stimulus (Stimulus Preceding
      Negativity, SPN). Spatiotemporal dipole modelling is used to gain insight in the
      possible generators of MPN and SPN. From the models it follows that the MPN can
      be described by one contralateral radial dipole and a bilateral pair of
      tangential dipoles. All three dipoles are located near central electrode
      positions, so the generators of the MPN probably reside within the motor cortex.
      The SPN is modelled by a bilateral frontotemporal pair of dipoles, hypothetically
      representing activation of the Insulae Reili. The insular cortex is involved in
      the processing of affective-motivational input, such as carried by the feedback
      in the present paradigm. However, processing of the information content of the
      feedback stimulus might by itself also activate the frontal cortex. Both the
      response and the feedback stimulus are followed by a positive peak, which can be
      described by the same deep posterior dipole. Both peaks probably represent a P3,
      which is related to context updating.

PMID- 7803204
TI  - Multivariate composite estimators: new ways to track signals with application to
      human cerebral potentials.
AB  - In this paper, we propose new multivariate composite estimators (MCE) to track
      multiple channel potential waves of individual and grand averages of recorded
      potentials at the scalp from a number of trials in a group of subjects. The
      advantages of these estimators over simple averages used in the literature are
      that they have larger signal to noise ratios (SNR), and that they have taken into
      account variations and correlations of the recorded potentials at the electrode
      sites as well as differences among subjects. Multivariate techniques and
      composite concept are used for deriving the estimators. We also provide an
      application to human event-related potentials in a memory for faces experiment.

PMID- 7803205
TI  - [Surgery of rectal cancer: lymphadenectomy and nerve sparing technique].

PMID- 7803206
TI  - [Clinical-experimental models for the identification of immunologic parameters to
      be integrated in traditional staging systems of colorectal neoplasms].
AB  - The Authors evaluate new possible models for the staging of colorectal cancer
      based on clinico-morphological, histo-pathological and bio-immunological
      parameters. Particularly, they evaluate the possibility of studying host's
      immunological response against tumor spread by the examination of the "in situ"
      cellular responses. This study was performed by cytotoxic test and
      immunohistochemical evaluation of the lymphocytes. The latter seems to give
      better results compared to the first in the evaluation of the host's
      immunological response.

PMID- 7803207
TI  - [Neoplastic involvement of the inferior vena cava].
AB  - Inferior caval vein invasion not infrequently complicates advanced neoplastic
      lesions. Primitive caval neoplasms (leiomyosarcomas) or other tumors such as
      renal carcinomas, pheochromocytoma, as well as liver, testis, and retroperitoneal
      tumors most likely cause caval invasion. In the past, caval invasion was a clear
      index of non operability, while today, a modern multidisciplinary approach allows
      to treat successfully even so advanced diseases. In the present report the
      Authors analyze the cases treated at the Dept. of Surgery of the University of
      Perugia, and review the most important international reports on this subject
      illustrating the new possibilities offered by IVC substitution with biological or
      artificial grafts.

PMID- 7803208
TI  - [Mondor's disease: our experience].
AB  - Mondor's disease is commonly described as thrombophlebitis of the subcutaneous
      veins of the chest. It is a relatively uncommon syndrome, generally considered of
      trivial importance for its poor symptoms: local pain, rarely fever. Recovery is
      obtained in one or two months with adequate medical treatment. Common causes are
      traumas, surgery, stress, breast phlogosis; however, some Authors still consider
      the syndrome as a sinchronous breast cancer "marker".

PMID- 7803210
TI  - [Echographic evaluation of goiter recurrence].
AB  - Ultrasound is mandatory in the follow up of patients surgically treated for
      benign thyroid diseases. In this study the Authors have examined 87 patients who
      underwent different surgical treatments for goiter over 40 years. Ultrasound
      allowed a more accurate study of residual thyroid, particularly evaluating
      thyroid tissue morphology in symptomatic patients (43.6%) and detecting many
      recurrences in asymptomatic patients (37.3%). This study also confirms the
      advantage of a more extensive surgery to reduce recurrences without increasing
      complications.

PMID- 7803211
TI  - [Percutaneous endoscopic gastrostomy (PEG)].
AB  - When gastric decompression or enteral feeding are needed for patients affected by
      neurological problems or neoplasias with a long life expectancy (months), PEG
      represents the method of choice because it has a lesser number of complications,
      needs a mild sedation, and has a lower cost compared to surgical techniques.

PMID- 7803212
TI  - [Ambulatory treatment of postphlebitic ulcers of lower limbs. Physiopathological
      bases and clinical results].
AB  - Venous ulceration is a troublesome and disabling complication, representing one
      of the most difficult problems to be treated by the vascular surgeon. Venous
      insufficiency is a widespread condition, the prevalence of venous ulceration
      being 0.5 - 1 per cent in European populations. Although all venous ulcers will
      heal if the limb is elevated above heart level for an extended period of time,
      patients need a safe, effective, not disabling and quick therapy. Hence, the
      competent vascular surgeon must be familiar with venous pathophysiology and
      possess a thorough understanding of the treatment options available for a
      discouraged patient in need of an acceptable and effective approach. The aim of
      the present study was to assess the efficacy and the speed of healing of venous
      ulcer using an outpatient ambulatory treatment protocol. This protocol consisted
      of elastic compression bandage allowing deambulation, local dressing using
      lyophilized heterologous collagen (Condress, Gentili) and systemic
      profibrinolytic drugs. Exclusion criteria were coexisting arterial insufficiency,
      ulcer area greater than 25 cm2, coexisting disabling diseases (congestive cardiac
      failure, hepatic insufficiency, malignancy). From December 1990 to June 1993, 37
      patients affected by venous ulcer were treated, according to the aforementioned
      protocol, at the Surgical Department of Montecchio Maggiore Hospital (VI). There
      were 16 male and 21 female patients, mean age was 66 years (range 59-91). Results
      show the complete healing of the venous ulcer in 94.5% of patients; mean time for
      ulcer healing was 128 days (range 45-91). The Authors conclude that the
      outpatient ambulatory treatment protocol is safe, quick, and effective for the
      therapy of chronic venous ulcer; once obtained the healing of the ulcer, elastic
      compressive bandage with elastic stockings is mandatory to prevent recurrences.

PMID- 7803209
TI  - [Prevention of post-ERCP acute pancreatitis with octreotide].
AB  - Acute pancreatitis is one of the most serious complications in endoscopic
      cholangio-pancreatography (ERCP) and endoscopic sphincterotomy (EPT). Many
      attempts to avoid such complication have proved to be unsuccessful. The aim of
      this study was to evaluate the therapeutic effect of octreotide acetate in
      preventing acute pancreatitis following ERCP. The study was carried out over 100
      patients, randomly allocated in two groups. The first group of patients (50 pt.)
      received 0.1 mg of octreotide acetate s.c. 45 minutes before the ERCP, followed
      by another dose given 6 hours later. The second group received placebo s.c.

PMID- 7803214
TI  - How long should adjuvant tamoxifen be continued?
AB  - Tamoxifen can reduce the risk of relapse and death from breast cancer when used
      as adjuvant therapy for early stage breast cancer. While most trials have tested
      1 or 2 years of therapy, it is now common to continue tamoxifen for 5 or more
      years. However, the optimal duration remains controversial. The complex
      physiologic and clinical effects of tamoxifen cannot be fully predicted by our
      rudimentary understanding of its basic mechanisms of action. An analysis of
      randomized clinical trials comparing different tamoxifen durations is therefore
      necessary. Individual patients' risks of breast cancer recurrence, other
      beneficial effects, and potential toxicities also must be entered into the
      decision-making process.

PMID- 7803213
TI  - [A specific technique for ileo-anal anastomosis in restorative proctocolectomy:
      physiopathological evaluation and results].
AB  - The Authors report an alternative technique for ileo-anal anastomosis in total
      proctocolectomy with ileal pouch. Their experience and results are discussed.

PMID- 7803215
TI  - Clinical trials referral resource. Primary central nervous system tumors.

PMID- 7803216
TI  - The molecular genetics of gyn malignancies.
AB  - Gynecologic malignancies, representing 13% of all cancers affecting women, have a
      major impact on women's health. Cervical, endometrial, and ovarian cancers
      comprise the majority of these tumors and contribute significant morbidity and
      mortality to the female population. While cervical and endometrial cancers can be
      detected early in their development, sadly, many patients present with advanced
      disease, as do the majority of patients with ovarian cancer. Unfortunately,
      advanced cases of these malignancies are usually lethal despite modern
      therapeutic modalities. In order to impact upon these grim statistics,
      gynecologic researchers have turned to molecular biology in an attempt to
      elucidate the etiology of these cancers. Recent research describing dominant
      oncogene and tumor suppressor gene mutations common to these malignancies is
      providing a basis for the molecular genesis of these cancers. This information
      should offer new avenues for the development of early detection and
      chemoprevention, as well as novel treatment strategies.

PMID- 7803217
TI  - Radiotherapy with or without neck dissection treatment of choice for base of
      tongue cancer.

PMID- 7803218
TI  - Psychosocial sequelae of bone marrow transplantation.
AB  - Bone marrow transplantation is a particularly arduous treatment and a source of
      considerable stress for patients and their families. Psychological sequelae
      include psychological distress, concern about loss of control, physical
      complications, sexual dysfunction, difficulties in social relationships,
      occupational disability, and financial consequences. Patient education that can
      help BMT recipients and their families know what to expect at the different
      stages of treatment may help alleviate anxiety and fear of the unknown.
      Communication should be individualized according to the needs of the particular
      patient and family. The patient's ability to use information should be considered
      in deciding what to convey to him or her. To be most effective, patient education
      should take place throughout the BMT process and should be multidisciplinary.

PMID- 7803219
TI  - World malaria situation in 1992. Part II. Asia west of India.

PMID- 7803220
TI  - Plague. International team of experts.

PMID- 7803221
TI  - Cholera in Europe.

PMID- 7803222
TI  - Black & ethnic minority clients: meeting needs (continuing education credit).

PMID- 7803223
TI  - Ultraviolet A phototherapy and trimethylpsoralen UVA photochemotherapy in
      polymorphous light eruption--a controlled study.
AB  - Twenty-two patients with polymorphous light eruption were prophylactically
      treated with ultraviolet A (UVA) with and without trimethylpsoralen in the first
      randomized double-blind study in this subject. Twelve of the patients were
      treated during 2 consecutive springs with placebo during one spring and psoralens
      during the other. Eighteen of the patients improved after the therapy, but there
      was no clear-cut difference between the 2 regimens. As many as 12 patients got
      light eruptions during the treatment, but all but one continued with the therapy.
      This study indicates that UVA alone is as good prophylactic therapy for
      polymorphous light eruption as PUVA with trimethylpsoralen. However, because of
      the high incidence of provoked eruptions during therapy, the treatment may be
      difficult to handle for the patients themselves, at least during the initial
      treatment.

PMID- 7803224
TI  - Photocontact allergy to oxybenzone: ten years of experience.
AB  - Intolerance of sunscreen agents has often been reported in the literature. This
      mainly comprises photosensitization to sunscreens such as oxybenzone. The aims of
      this study were to establish the incidence of photocontact allergy to oxybenzone
      and its relationship with the use of other cosmetics. From 1982 to 1992 we
      performed photopatch tests on 283 patients with suspected photodermatosis. Forty
      six patients (16%) had positive reactions: 61 positive photopatch tests and 9
      positive patch tests. Photocontact allergy to sunscreens was divided into 2 main
      groups: 35 cases to oxybenzone and 17 cases to para-aminobenzoic acid and its
      derivatives. Among our 35 cases of photoallergy to oxybenzone, more than one
      third had photoallergy to a daily moisturizer that contained oxybenzone.

PMID- 7803225
TI  - Changing the risk spectrum of injury and the performance of sunscreen products
      throughout the day.
AB  - Sunscreen products are tested normally against a defined solar simulator spectrum
      that, in ultraviolet (UVB), closely resembles the noontime spectral composition
      of summer sunlight. Although such a spectrum may define the product for use in
      the most adverse sunlight conditions, little attention has been given to how such
      products perform against other natural sunlight spectra. Outdoor clinical trials
      suggest that indoor testing of sunscreens may overestimate the performance of
      many products. In this study we compared the predicted efficacy of specific
      products to a variety of natural sunlight spectra taken at different solar angles
      and under different atmospheric conditions. We found that a standard product
      always provides less protection for a natural sunlight spectrum than its label
      value would suggest. The deviation from the labeled value is the greatest when
      the sun is low in the sky, i.e., close to the horizon. The deviation is due to
      the changing ratio of UVA to UVB radiation in natural sunlight. The deviation can
      be as large as a factor of 2.0.

PMID- 7803226
TI  - Effects of hypnotic suggestions on ultraviolet B radiation-induced erythema and
      skin blood flow.
AB  - Results from both animal and human studies have indicated that inflammatory skin
      reactions such as the flare response to histamine prick test involve a neurogenic
      regulatory component. It is still unknown to which degree inflammation induced by
      ultraviolet (UV) radiation may be mediated by the central nervous system. To
      investigate this, the effect of hypnotic suggestions to increase and decrease the
      response to UVB radiation on erythema and cutaneous blood flow was investigated
      in 10 highly hypnotizable subjects. The results showed a significant effect of
      hypnotic suggestions on cutaneous blood flow compared with the responses of a
      control group. For erythema no conclusive evidence was found. The results
      indicate the possibility of separate regulatory mechanisms behind central nervous
      system influence on UVB-induced erythema and skin blood flow respectively, and
      further investigations are needed.

PMID- 7803227
TI  - Topical application of isotretinoin did not modify human Langerhans cell
      allostimulatory function.
AB  - The beneficial effect of isotretinoin on the repair of photodamaged skin is well
      documented. Little is known, however, on the action of this compound on
      immunological functions of epidermis. In a double-blind study, we analyzed the
      effect of topical applications of isotretinoin on human Langerhans cell (LC)
      function by using the mixed epidermal cell lymphocyte reaction (MELR).
      Isotretinoin cream (0.1%) was applied daily for 4 months on the back of one hand
      of 5 healthy volunteers, 50-60 years of age. The back of the other hand received
      vehicle alone and was used as control. Skin biopsy specimens were taken at the
      end of treatment. Epidermal cell (EC) suspensions were obtained by the use of
      trypsin and allogeneic T cells were purified from the peripheral blood of
      allogeneic donors. MELR was performed in microtiter plates and T cell
      proliferation was assessed by 3H-thymidine incorporation during the last 18 h of
      culture. Results did not show any differences between allogeneic T cell responses
      to EC from isotretinoin-treated or nontreated skin. These results therefore
      suggest that isotretinoin, applied topically onto photodamaged skin, did not
      alter human LC antigen-presenting function.

PMID- 7803228
TI  - Noninvasive measurement of the effect of lifetime exposure to the sun on the aged
      skin.
AB  - The cumulative and comparative effects of chronological and actinic changes to
      the skin were studied in an elderly population. Two adjacent sites with different
      degrees of exposure to the sun were examined to distinguish the contribution of
      each factor, by means of noninvasive measurements. The following parameters were
      measured on the skin of the low neck (an exposed site), as well as on the
      adjacent clothes-protected skin of 30 elderly women: electrical conductance,
      color, microrelief, biomechanical properties and the thickness of both the full
      skin and the subepidermal nonechogenic band (SENEB), using ultrasound
      measurements. Persistent exposure to the sun accentuated most of the age-induced
      modifications. The following changes were significantly more marked in exposed
      skin: SENEB thickening, full-skin thinning, loss of extensibility and elasticity,
      and color heterogeneity. The cumulative effects of sun exposure and chronological
      aging lead to atrophy in elderly people. These results suggest that, if there is
      an autoprotective skin reaction, such as thickening in young adults, it is
      eliminated in old people.

PMID- 7803229
TI  - Pathogenesis of idiopathic myelofibrosis: present status and future directions.

PMID- 7803230
TI  - Unique immunophenotype of acute promyelocytic leukaemia as defined by CD9 and
      CD68 antibodies.
AB  - Twenty-one cases of acute promyelocytic leukaemia (FAB M3) demonstrating t(15,17)
      chromosomal translocation were studied in detail by immunocytochemical techniques
      using a panel of monoclonal antibodies. A characteristic myeloid phenotype of the
      leukaemic cells, co-expression of CD9 and CD68 antigens and absence of HLA-DR,
      was noted in all cases. Although the cellular morphology of acute promyelocytic
      leukaemia provides the most rapid means for diagnosis, this unique leukaemic cell
      phenotype provides confirmatory diagnostic evidence. In view of the new
      therapeutic options and prognosis in acute promyelocytic leukaemia, the detection
      of cases with atypical morphology based on this unique phenotype would be of
      value. In addition, the phenotype of acute promyelocytic leukaemia is similar to
      that of basophils and mast cells and raises the possibility that the leukaemic
      cells may have undergone a degree of basophilic differentiation.

PMID- 7803231
TI  - The relationship between bcl-2 expression and response to chemotherapy in acute
      leukaemia.
AB  - Immunocytochemistry was used to assess bcl-2 expression in blasts obtained from
      the bone marrow of 28 patients with acute lymphoblastic leukaemia (ALL) (16
      children and six adults at presentation and three children and three adults on
      relapse) and 20 with acute myeloid leukaemia (AML) (19 adults and one child, 13
      with de novo AML, 11 at presentation and two on relapse, and seven secondary to
      myelodysplasia or chronic myeloid leukaemia). Slides were examined both for the
      percentage of positive cells and for the intensity of staining using a five-point
      scale. There was a statistically significant increase in both the percentage of
      positive cells seen (P < 0.002) and the intensity of staining (P < 0.01) between
      samples obtained at relapse and those at presentation in ALL. There was a
      significantly greater intensity of staining in cells from patients with ALL (P <
      0.05) and AML (P < 0.05) who failed to achieve remission after chemotherapy than
      in those who responded. The intensity of staining in cases of secondary AML was
      lower than that in de novo disease (P < 0.01). These results suggest that
      expression of bcl-2 may be an important prognostic feature in both de novo AML
      and in ALL, but not in secondary AML.

PMID- 7803232
TI  - Molecular detection of clonally rearranged cells in peripheral blood progenitor
      cell harvests from multiple myeloma patients.
AB  - Peripheral blood progenitor cells (PBPC) are increasingly used for autologous
      reconstitution following high-dose chemotherapy in multiple myeloma but it is
      unclear whether these cells are less likely to be contaminated with malignant
      cells than bone marrow (BM). We have investigated this using immunoglobulin heavy
      chain (IgH) gene fingerprinting, a polymerase chain reaction based technique with
      a sensitivity of 0.1-0.01% (10(-3)-10(-4)). We have looked for patient-specific
      IgH rearrangements in leukapheresis samples from eight myeloma patients
      undergoing PBPC harvest. Seven were in first remission (six partial, one
      complete) and one in second complete remission. Mobilization of PBPC was
      accomplished using cyclophosphamide (4 or 7 mg/m2) and rhG- or GM-CSF. Between
      two and five leukaphereses were performed in each patient. Patient-specific IgH
      rearrangements were identified in diagnostic BM in all patients and bands of
      identical size were found in one or more leukaphereses from 6/8 patients.
      Overall, 14/32 leukaphereses were shown to be contaminated. Two patients who
      showed contamination of at least one PBPC harvest had BM harvests in which
      contaminating cells were not detectable, suggesting that PBPC are not necessarily
      less likely to be contaminated than marrow stem cells. These results indicate
      that PBPC harvests from the majority of myeloma patients are likely to contain
      contaminating cells. Further studies are needed to determine whether these cells
      are clonogenic and whether they contribute to relapse.

PMID- 7803233
TI  - Impact of response to treatment on survival in multiple myeloma: results in a
      series of 243 patients.
AB  - Two hundred and forty-three patients diagnosed with multiple myeloma (MM) in a
      single institution over a 22-year period and treated with standard chemotherapy
      were analysed in an attempt to determine the impact of response to therapy on
      survival. The overall response rate in 229 evaluable patients was 50.1% (34.9%
      objective response plus 15.2% partial response). Median survivals of patients
      with objective and partial response were 43.4 and 42.8 months, respectively,
      versus 19 months for nonresponders. Median survival of 14 patients who achieved a
      complete remission was 42 months, whereas in 21 rapid responders (< or = 2
      months) median survival was 43.3 months. A significant correlation between
      response and survival was observed with the landmark (P = 0.0169), the Mantel &
      Byar (P = 0.0001) and the Cox regression model (P < 0.0001) methods. These
      results indicate that, in responding patients, neither the degree of response nor
      the response kinetics has a significant influence on survival. However, the
      response to therapy is associated with a significantly longer survival in MM
      patients.

PMID- 7803234
TI  - Efficient gene transfer into human umbilical vein endothelial cells allows
      functional analysis of the human tissue factor gene promoter.
AB  - Tissue factor (TF) is a cellular receptor and cofactor for factor VII/VIIa which
      initiates the blood coagulation cascade. We have investigated the role of 5'
      flanking DNA sequences in regulating the expression of the human TF gene in human
      umbilical vein endothelial cells (HUVEC). Using a chloramphenicol
      acetyltransferase (CAT) reporter gene, we attempted to transfect primary cultured
      HUVEC (passage 3-4) with calcium phosphate coprecipitation, DEAE Dextran,
      lipopolyamine-coated DNA or electroporation. Electroporation in HEPES-buffered
      saline of 1 x 10(7) cells at 200V and 250 microF was found to be optimal. Using
      these conditions, varying lengths of TF 5'-flanking sequences coupled to the CAT
      reporter gene were tested in transient expression studies. CAT expression
      corrected for variation in transfection efficiency and cell viability revealed
      that the sequences between -111 and +14 base pairs are essential for minimal
      transcriptional activity. This region contains consensus sequences for a TATA box
      and three Sp1 binding sites. A domain from -382 to -111bp, which contains two AP
      1 consensus elements, promoted high levels of gene expression. This
      transcriptional activity was repressed by 50% with constructs containing
      sequences between -550 and -382 bp. A further 2-fold drop in transcription
      activity was attributed to the region between -948 and -550 bp. These results
      suggest that the basal transcription of the human TF gene in HUVEC is mediated
      through at least two negative regulatory elements upstream of the proximal
      promoter domain. The proximal promoter region which contains two AP-1 sites is
      essential for efficient transcription.

PMID- 7803235
TI  - A haemorrhagic platelet disorder associated with altered stimulus-response
      coupling and abnormal membrane phospholipid composition.
AB  - Haemorrhagic diatheses due to platelet function defects are a heterogenous and
      poorly understood group of conditions. We report the investigation of a female
      with a lifelong history of epistaxes, haemarthroses, menorrhagia and persistent
      iron-deficiency anaemia. Although platelet numbers and morphology were normal,
      platelet function was abnormal both in vivo and in vitro. Skin bleeding time was
      prolonged and aggregation thresholds in platelet-rich plasma to a variety of weak
      and strong agonists were increased. Platelet granule contents were normal and
      membrane glycoproteins GpIb and GpIIIa were present in normal amounts.
      Polyphosphoinositide metabolism and phosphatidic acid generation were diminished
      in thrombin-stimulated platelets, as was phosphorylation of the 47 kD substrate
      for protein kinase C and the 20 kD protein myosin light chain kinase, indicating
      impaired generation of the intracellular second messengers diacylglycerol and
      inositol trisphosphate due to diminished stimulated phospholipase C activity.
      Although intracellular free calcium, calmodulin activity and basal cAMP
      concentrations were normal, washed platelets showed increased cAMP accumulation
      following stimulation with prostaglandin E1 and forskolin. Platelet membrane
      lipid analysis revealed a reduction in plasmalogen phosphatidylethanolamine
      content. It is suggested that the membrane phospholipid abnormalities cause the
      abnormal platelet reactivity by interfering with signal transduction from
      platelet receptor, via intermediary G proteins, to phospholipase C and adenylate
      cylase. The bleeding tendency is likely to be a consequence of the altered
      stimulus-response coupling.

PMID- 7803236
TI  - Influence of combined thrombin stimulation, surface activation, and receptor
      occupancy on organization of GPIb/IX receptors on human platelets.
AB  - Down-regulation and clearance of as many as 60-80% of GPIb/IX receptors from
      exposed surfaces on thrombin-activated platelets to channels of the open
      canalicular system (OCS) is considered to be a fundamental mechanism regulating
      platelet adhesivity in vitro and in vivo. The present study has combined thrombin
      stimulation in suspension, surface activation on formvar grids, receptor
      occupancy by von Willebrand factor (vWF) and exposure to anti-vWF antibody in an
      effort to demonstrate the removal of GPIb/IX receptors from activated cells.
      Individually the stimuli failed to cause any change in the frequency of GPIb/IX
      receptors. Combined, the stimuli were no more effective than when each was used
      alone. The only way to cause GPIb/IX to move was to add anti-vWF to thrombin
      activated platelets allowed to spread on formvar grids and covered with multimers
      of ristocetin-activated human or bovine vWF. Translocation of GPIb/IX-vWF-anti
      vWF complexes from peripheral margins into caps over cell centres, however, did
      not clear the peripheral zone of vWF binding capacity. Exposure of capped
      platelets after fixation to a second incubation with vWF demonstrated as many
      multimers extending from the central cap to the peripheral margins as were seen
      on platelets exposed a single time to vWF. Antibodies to GPIb, but not to
      GPIIb/IIIA, prevented the second labelling by vWF. Down-regulation or clearance
      of GPIb/IX, in light of this study, does not appear to be a fundamental mechanism
      modulating platelet adhesivity.

PMID- 7803237
TI  - Dissociation between the phospholipases C and A2 activities in stimulated
      platelets and their involvement in the arachidonic acid liberation.
AB  - In previous work we have demonstrated that platelets depleted from secretory
      phospholipase A2 (sPLA2) produced similar amounts of thromboxane (Tx)B2 as
      control platelets upon stimulation by thrombin. However, since depletion of sPLA2
      was not total, this sole finding only suggested the non-involvement of sPLA2 in
      arachidonic acid release. In the present study we provide further evidence for
      the non-involvement of sPLA2 in arachidonic acid liberation during platelet
      activation. Thus, rabbit platelets exposed to thrombin secreted sPLA2, released
      free arachidonic acid and formed TxB2 and inositol phosphates. In contrast,
      U46619, a stable prostaglandin (PG)H2 analogue, activates phospholipase C (PLC)
      and induces release of sPLA2 without TXB2 generation nor arachidonic acid
      liberation. At each concentration tested of both agonists, stimulation of sPLA2
      activity paralleled the production of inositol phosphates. These data suggest
      that sPLA2 is dependent on phosphoinositide hydrolysis and on the release
      reaction and that it is not involved in the liberation of arachidonic acid from
      stimulated platelets. In addition, a dissociation was observed between sPLA2 and
      the enzyme involved in the arachidonic acid mobilization, suggesting that the
      liberation of this fatty acid from membrane phospholipids was mediated by
      cytosolic phospholipase A2 (cPLA2). Finally, PLC does not play a major role in
      arachidonic acid liberation, since U46619, which induced the breakdown of
      inositol phospholipids, failed to release arachidonic acid. In confirmation,
      neomycin, which inhibits PLC activity, failed to inhibit ATP, sPLA2 and
      arachidonic acid release upon stimulation of platelets by fluoroaluminate. These
      data demonstrate that sPLA2 is not involved in the arachidonic acid release by
      stimulated platelets and indicate that the activations of PLC, sPLA2 and cPLA2
      are independent events.

PMID- 7803238
TI  - Factor IX Bm Kiryu: a Val-313-to-Asp substitution in the catalytic domain results
      in loss of function due to a conformational change of the surface loop: evidence
      obtained by chimaeric modelling.
AB  - Factor IX Kiryu is a naturally occurring mutant of factor IX that has 2.5%
      coagulant activity, even though normal plasma levels of factor IX antigen are
      detected. Factor IX Kiryu was purified from a patient's plasma by immunoaffinity
      chromatography with a calcium-dependent anti-factor IX monoclonal antibody
      column. It was cleaved normally by factor XIa in the presence of Ca2+, yielding a
      two-chain factor IXa. However, the resulting factor IXa showed only 1.5% of the
      normal factor IXa in terms of factor X activation in the presence of factor VIII,
      phospholipids, and Ca2+, and had 20% of the normal esterase activity for Z-Arg-p
      nitrobenzyl ester. Therefore factor IXa Kiryu showed the defect of the catalytic
      triad or primary substrate binding site as well as defective interaction with
      factors VIII/X. Single-strand conformational polymorphism analysis and DNA
      sequencing of the amplified DNA revealed a missense point mutation, a T-to-A
      substitution at nucleotide number 31,059 of the factor IX Kiryu gene. This
      mutation resulted in the amino acid substitution of Val-313 by Asp in the
      catalytic domain. Restriction enzyme analysis of the amplified DNA showed that
      the mutation was inherited from the patient's mother. The chimaeric method was
      employed to construct a model of the serine protease domain of factor IXa, and
      the resultant model suggested that the Val-313 to Asp substitution altered the
      conformation of the substrate-binding site. These data combined with our previous
      findings on a Gly-311-to-Glu mutant of factor IX suggest that the loop
      conformation from Gly-311 to ARg-318 is important for the expression of coagulant
      activity.

PMID- 7803239
TI  - Tumour necrosis factor-alpha and interleukin 4 promote the differentiation of
      myeloma cell precursors in multiple myeloma.
AB  - The effects of tumour necrosis factor-alpha (TNF-alpha) and interleukin 4 (IL-4)
      on peripheral blood mononuclear cells (PBMC) from 36 patients with multiple
      myeloma (MM), 12 with monoclonal gammopathy of undetermined significance (MGUS)
      and 21 normal controls, were investigated. In 16/36 patients with MM, monoclonal
      plasma cells appeared after 4d in cultures containing TNF-alpha and IL-4. These
      changes were not observed in PBMC from patients with MGUS or from normal
      controls. These findings suggest that myeloma cell precursors do exist in the
      peripheral blood of MM patients and differentiate into plasma cells in the
      presence of TNF-alpha and IL-4. Based on these observations, we think that the
      variation in the number of myeloma cell precursors in peripheral blood could be
      used as a prognostic parameter of response to chemotherapy in myeloma patients.
      In addition, this assay may be useful to distinguish early-stage MM from MGUS.

PMID- 7803240
TI  - Red blood cell aggregability in patients with a history of leg vein thrombosis:
      influence of post-thrombotic treatment.
AB  - Reversible aggregation of red blood cells (RBC) plays an important role in
      determining blood flow properties, and it is this aggregation which increases
      blood viscosity at low shear rates. The structure and sites of venous thrombi, as
      well as the fact that stasis is a major predisposing factor in venous thrombosis,
      suggest a strong association between vein thrombosis, slow blood flow and
      increased blood viscosity. RBC aggregation and disaggregation were measured
      (SEFAM erythroaggregameter, France) in 54 patients with a history of unexplained
      leg vein thrombosis. Results were compared to those of controls classified
      according to age. Increased RBC aggregability was observed in 41% of the
      patients, and the mean values indicated a significant elevation of RBC
      aggregability in patients when compared with controls (P < 0.05). Subgroups were
      compared to study the influence of thrombus recurrence and thrombosis type (deep
      versus superficial vein thrombosis) on the aggregation parameters. No significant
      difference was found between these subgroups. The use of compression stockings
      and veinotropic drugs tended to reduce the abnormalities in RBC aggregability (P
      < 0.05). An increase in RBC aggregability and in the shear resistance of RBC
      aggregates, by predisposing to circulatory stasis, is likely to contribute to the
      evolution and complications of leg vein thrombosis.

PMID- 7803241
TI  - Characterization of human blood group scFv antibodies derived from a V gene phage
      display library.
AB  - We previously reported the initial characterization of five human single-chain Fv
      (scFv) antibody fragments specific for the blood group antigens B, D(Rh), E(Rh),
      Kpb and HI. The scFvs were isolated from a phage-antibody library constructed
      from the variable region genes of two non-immunized donors. In this paper we
      report the specificity, affinity and kinetics of antigen binding of these scFv
      fragments. All five scFvs agglutinated the appropriate red cell phenotype
      following the addition of a monoclonal antibody which recognizes a peptide tag
      incorporated into the scFv. The anti-B and anti-HI scFv molecules, which
      recognize high density carbohydrate antigens, spontaneously polymerized and
      agglutinated red cells directly. None of the antibody fragments showed cross
      reactivity with other red cell antigens, with the exception of the anti-E which
      reacted weakly with E-negative cells. Specific scFv binding was confirmed by
      ELISA, flow cytometry and radioactive labelling. The anti-D scFv recognized
      17,600 sites on cDE/cDE red cells with an association constant (Ka), of 5.2 x
      10(7) M-1 and a rate constant for dissociation (koff) of 1.9 x 10(-2) s-1. The
      anti-E scFv recognized 29,800 and 39,800 sites on cDE/cDE red cells in two
      experiments with Kas of 8.4 x 10(6) and 4.4 x 10(7) M-1. The koff for this
      antibody was 2.7 x 10(-2) s-1. The results demonstrate that scFv antibody
      fragments specific for cell surface antigens and possessing affinities typical of
      the primary immune response can be obtained from a phage-display library.

PMID- 7803242
TI  - Detection of herpesvirus type 6 by polymerase chain reaction in blood donors:
      random tests and prospective longitudinal studies.
AB  - In order to evaluate the prevalence of HHV-6 in blood donors, we examined 112
      persons by polymerase chain reaction (PCR) and ELISA. HHV-6 antibodies could be
      detected in 107/111 (96.4%) of the donors. The median ELISA antibody level was
      0.451 (range 0.056-0.914). 14 individuals (12.5%) were PCR positive in either
      oral lavage fluid, urine or buffy coat. Six persons (5.4%) were PCR positive in
      buffy coat samples. The prospective longitudinal analysis of 11 donors for
      periods between 7 and 13 weeks revealed that 4/6 persons who were initially PCR
      negative had positive tests in 9/63 weeks studied. Two persons were consistently
      PCR positive over the whole observation period of 12 and 13 weeks. HHV-6 variants
      could be determined in 14 persons as variant A in nine and variant B in five
      cases. These observations emphasize the high prevalence of HHV-6 and suggest that
      some blood donors carry detectable concentrations of the virus and therefore may
      be a source for transmission of HHV-6. The finding of positive PCR in antibody
      negative individuals suggests that antibody determination may not be sufficient
      to identify potentially infectious persons.

PMID- 7803243
TI  - PCR-based determination of Rhc and RhE status of fetuses at risk of Rhc and RhE
      haemolytic disease.
AB  - After anti-RhD, anti-Rhc is the most important red cell alloantibody which can
      cause haemolytic disease of the newborn (HDN) when the mother is Rhc-negative and
      the fetus Rhc-positive. We report here the development of polymerase chain
      reaction (PCR) assays which detect the presence of the Rhc alleles in amniotic
      cells by the use of allele-specific primers (ASP). It is expected that such
      determination will help in the management of pregnancies at risk of Rhc
      haemolytic disease. In the course of this study we have similarly performed PCR
      ASP experiments to detect fetal RHE alleles since, in rare cases, anti-RhE can
      also cause HDN.

PMID- 7803244
TI  - Acute myeloid leukaemia with +i(12p) shortly after treatment of mediastinal germ
      cell tumour.
AB  - We report a patient who developed acute myeloid leukaemia (M2) shortly after
      successful treatment of a mediastinal germ cell tumour. The leukaemia was
      preceded by a documented myelodysplastic phase. Complex cytogenetic abnormalities
      were found in bone marrow and peripheral blood cells including +i(12p), typical
      of germ cell malignancy. Fluorescence in situ hybridization revealed the presence
      of +i(12p) in myeloblasts, erythroblasts and neutrophils but not in lymphocytes.
      This case provides further evidence for a common clonal origin of haematological
      malignancies and mediastinal germ cell tumours.

PMID- 7803245
TI  - Further evidence that activated protein C resistance can be misdiagnosed as
      inherited functional protein S deficiency.
AB  - A recent report that activated protein C (APC) resistance interferes with
      functional protein S (PS) assays prompted us to re-investigate two pedigrees
      previously diagnosed as having functional PS deficiency. APC resistance was
      demonstrated in all individuals with apparent functional PS deficiency. The
      latter diagnosis was shown to be due to the assay being non-linear, functional
      protein S becoming normal at higher dilutions. This observation, taken in
      conjunction with results of in vitro recovery studies with purified PS, leads us
      to conclude that APC resistance was the primary disorder in both pedigrees. The
      misdiagnosis of APC resistance as functional PS deficiency can be prevented by
      performing the PS assay at several dilutions, including concentrations lower than
      those recommended by PS assay manufacturers. Subjects previously diagnosed as
      having functional PS deficiency should be re-investigated for APC resistance.

PMID- 7803246
TI  - High-dose gamma-globulin therapy in the reactive haemophagocytic syndrome.
AB  - Reactive haemophagocytic syndrome (RHS) is a disorder characterized by systemic
      proliferation of non-malignant histiocytes occurring most commonly in patients
      with pre-existing immunological abnormalities or neoplasms. Patients,
      particularly those with immunosuppression, often have a rapidly progressive fatal
      course. Treatment is directed at the underlying disorder. In the absence of
      identifiable cause, the therapy is less satisfactory. We report here three cases
      of RHS successfully treated with high-dose gamma-globulin therapy. Two of the
      three patients were immunocompromised and the third occurred during pregnancy.
      The improvement occurred within 24-72 h and all patients recovered. High-dose
      i.v. gamma-globulin therapy may be beneficial in RHS.

PMID- 7803247
TI  - Prenatal diagnosis of congenital dysgranulopoietic neutropenia.
AB  - Congenital dysgranulopoietic neutropenia is a severe life-threatening disease
      characterized by specific dysmorphic granulocytes. Prenatal diagnosis of
      congenital neutropenia was reported first in 1983. In 1989 we reported a family
      with congenital dysgranulopoietic neutropenia in two siblings (one male and one
      female); in 1992 the mother became pregnant and prenatal diagnosis was performed
      by cordocentesis. The results we obtained from the fetus at risk enabled us to
      suggest that it was not affected, and we advised the parents that the pregnancy
      could continue: a healthy female was born. The neutrophil count at 2 and 4 months
      was normal.

PMID- 7803248
TI  - Immunoglobulin replacement in patients with chronic lymphocytic leukaemia: a
      comparison of two dose regimes.
AB  - Previous studies have shown that intravenous immunoglobulin (IVIg) therapy is
      useful prophylaxis against infection in patients with secondary
      hypogammaglobulinaemia due to a low-grade lymphoproliferative disease. This
      randomized double-blind study was undertaken to determine prospectively the dose
      regime required. 34 such patients received IVIg at either 500 or 250 mg/kg every
      4 weeks for 1 year. There was no significant difference in the rates of serious
      infections between the two groups of patients, which were well matched for
      disease and laboratory parameters. The rates of infection seen were similar to
      those in IVIg groups of previous studies and strikingly different from those in
      the placebo group in the previously randomized placebo-controlled study.

PMID- 7803249
TI  - Fluctuating symptomatic cryofibrinogenaemia in a patient with left atrial myxoma.
AB  - We report a case of left atrial myxoma associated with a fluctuating level of
      cryofibrinogen. Her initial symptoms and signs were consistent with primary
      cryofibrinogenaemia, but a repeat episode occurred without the cryofibrinogen
      being detectable. A more typically embolic cerebro-vascular accident (CVA)
      occurred, with the subsequent discovery of the patient's myxoma. The
      cryofibrinogen was again present but it disappeared with resection of the myxoma.
      We propose that the degree of activation of the coagulation system around the
      myxoma fluctuated, causing variable conversion of fibrinogen to fibrin, so that
      at times partially cross-linked fibrin(ogen) resulted in cryofibrinogen, but at
      other times frank emboli from more complete clotting occurred.

PMID- 7803251
TI  - Considerations on the true value of the international normalized ratio in the
      control of oral anticoagulant therapy.

PMID- 7803250
TI  - High prevalence of a mutation in the factor V gene within the U.K. population:
      relationship to activated protein C resistance and familial thrombosis.
AB  - Recent findings have indicated the importance of factor V (FV) in causing
      resistance to activated protein C (APC) in a high proportion of patients with
      venous thrombosis. This prompted us to investigate whether resistance could be
      due to defective inactivation of FVa by APC. Consequently, we amplified a 3.2 kb
      fragment of the FV gene sequence encoding the heavy chain APC cleavage site. DNA
      analysis showed a guanine to adenine transition at nucleotide 1691 in all
      affected members of two families with inherited APC resistance associated with
      thrombosis and confirmed suspected homozygosity in two individuals. The mutation,
      in heterozygous form, was also found in approximately 3.5% of our normal
      population (n = 144) and correlated with low APC resistance. The high prevalence
      of this mutation suggests that it may be a major contributory factor in early
      thrombosis.

PMID- 7803252
TI  - A mutation in the polyadenylation signal of the alpha 2 globin gene (AATAAA-
      >AATA--) as a cause of alpha thalassaemia in Asian indians.

PMID- 7803253
TI  - CD45 isoform expression on human haemopoietic cells at different stages of
      development.
AB  - Alternate splicing and glycosylation produce multiple CD45 isoforms which are
      selectively expressed on the surface of cells of the haemopoietic system. The
      expression of CD45RA, CD45RB and CD45RO on CD34+ and CD34- haemopoietic cells
      from umbilical cord blood, bone marrow and fetal liver were studied by flow
      cytometry. CD34+ subpopulations defined by CD45 isoform expression were sorted
      from bone marrow and tested in long-term culture assays. By combining results of
      functional studies with phenotypic data and previously published information, the
      following pattern of CD45 isoform expression on early haemopoietic cells was
      established. The most primitive CD34+ cells are CD45RO+ CD45RB+ and express low
      or undetectable levels of CD45RA. Upon erythroid differentiation, CD34+ cells
      remain CD45RO+ CD45RB+, whereas commitment into the myeloid and lymphoid lineages
      coincides with down-regulation of CD45RO and up-regulation of CD45RA. As a
      result, the majority of CD34+ cells can be divided into two mutually exclusive
      populations of cells which express either CD45RO or CD45RA. This notion was
      confirmed in this study by three-colour immunofluorescence. The alternative
      expression of various CD45 isoforms on functionally distinct haemopoietic cells
      suggests an important role for these molecules in the proliferation and
      differentiation of haemopoietic cells.

PMID- 7803254
TI  - Myeloid haemopoietic cells of patients with chronic granulomatous disease are
      relatively resistant to TNF.
AB  - Generation of superoxide may be a key step in the cytotoxicity mediated by tumour
      necrosis factor (TNF); cells that cannot produce oxygen radicals might be
      resistant to TNF. Myeloid haemopoietic cells from patients with chronic
      granulomatous disease (CGD) cannot produce a large burst of oxygen radicals;
      therefore we examined the ability of TNF to inhibit clonal growth of myeloid
      haemopoietic cells from patients and carriers with several types of CGD.
      Mononuclear light-density cells from the peripheral blood of 13 CGD patients (11
      patients with defects of gp91-phox and two with p47-phox), five gp91-phox
      carriers and 10 normal volunteers were cultured with the appropriate growth
      factor and TNF in methylcellulose. As expected, TNF (0.001-100 ng/ml) inhibited
      colony formation of myeloid cells of normal volunteers in a dose-dependent
      manner. In contrast, clonal growth of myeloid cells of CGD patients was resistant
      to inhibition by TNF < or = 100 ng/ml. As expected, the effects of TNF on
      erythroid clonogenic cells, which are not capable of producing an oxygen burst,
      and the action of TGF-beta on clonal growth of myeloid cells, were similar in
      both the individuals with CGD and the normal volunteers. In X chromosome-linked
      female carriers of CGD (gp91-phox deficiency), TNF showed an intermediate
      cytotoxicity on clonal growth of myeloid cells, and analysis of NBT reduction
      demonstrated that the colonies derived from myeloid cells deficient in gp91-phox
      were resistant to TNF and those derived from the myeloid cells expressing gp91
      phox were inhibited in their proliferation by TNF. This study shows for the first
      time that myeloid haemopoietic cells from patients with CGD are relatively
      resistant to the growth-inhibiting effects of high concentrations of TNF.

PMID- 7803255
TI  - Recovery of T-lymphocytes for adoptive immunotherapy by lymphapheresis of HIV
      infected patients without alterations of virological, immunological or clinical
      parameters.
AB  - We performed repeated continuous flow cytaphereses (CFC) on 13 asymptomatic HIV-1
      infected patients to study the feasibility of cell separation procedures to
      recover high yields of peripheral blood T-lymphocytes for adoptive immunotherapy
      in HIV-infected patients and to determine immunological and virological
      alterations following such procedures. A mean yield of 6.23 x 10(9) lymphocytes
      could be obtained by each cytapheresis, containing 1.82 x 10(9) CD4+, 3.23 x
      10(9) CD8+ T-lymphocytes and 8.39 x 10(6) CD34+ peripheral progenitor cells. The
      CD4/CD8 ratio (mean 0.53, SD +/- 0.15) in the cell samples reflected the
      distribution of the lymphocyte subsets in vivo. Absolute lymphocyte counts
      decreased at a mean of 404/mm3 (25%) immediately after CFC but were replaced from
      the extravascular pool within 1 h. The CD4/CD8 ratios, p24-antigenaemia, HLA-DR
      expression and neopterin levels did not change significantly after cell
      separation. No alteration of the number of T-cells with integrated proviral DNA
      copies (1/10(3) to 1/10(6)) could be detected in peripheral T-helper cells by PCR
      after lymphapheresis. We conclude that high yields of peripheral T-lymphocytes
      can be obtained by continuous flow lymphapheresis for cell-mediated
      immunotherapy, without deterioration of virological or immunological parameters
      in HIV-infected patients. The separated T-cells are fully replaced from
      extravascular pools after 1 h.

PMID- 7803256
TI  - Erythrocyte membrane protein alterations underlying clinical heterogeneity in
      hereditary spherocytosis.
AB  - Hereditary spherocytosis (HS) is a very heterogenous condition both at clinical
      and biochemical level. To establish the relationship between these aspects we
      performed a clinical and biochemical study in 87 Italian HS subjects. Patients
      were divided into three groups based on clinical severity (mild, typical and
      severe) and into five subgroups based on specific membrane abnormalities
      identified by polyacrylamide gel electrophoresis (isolated spectrin deficiency,
      spectrin deficiency combined with mild ankyrin reduction, spectrin deficiency
      combined with severe ankyrin reduction, band 3 reduction and isolated protein 4.2
      reduction). We were not able to assess any alteration in six HS patients. A good
      correlation between clinical HS forms and membrane protein defects is shown. We
      conclude that erythrocyte membrane analysis should be carried out after diagnosis
      of HS in order to predict the clinical course of the disease.

PMID- 7803257
TI  - The effect of iron overload and iron reductive treatment on the serum
      concentration of carbohydrate-deficient transferrin.
AB  - The concentration of carbohydrate-deficient transferrin in serum (CDT) has been
      used as a reliable indicator of recent alcohol consumption. We have investigated
      the utility of this laboratory test in 20 patients with hereditary
      haemochromatosis (HH) by simultaneous evaluation of serum concentrations of liver
      transaminases, gamma-glutamyl transpeptidase, iron, transferrin and assessment of
      the liver iron concentration by magnetic resonance imaging. 11 patients were re
      examined during iron depletion with phlebotomies. In all 11 patients intensive
      but not maintenance iron removal was associated with an increase in serum CDT, in
      three patients even to levels above the reference range. The mean serum CDT
      increased from 8.5 (SD 2.2) U/l to 16.6 (SD 7.2) U/l (P < 0.001). Iron
      mobilization from the liver was found particularly responsible for the increase
      in serum CDT. Independent of this finding we found a significant semi-logarithmic
      correlation (r = -0.77, P = 0.009) between the MRI determined liver iron
      concentration and serum CDT in the patients not on iron depletion. Our findings
      indicate that the utility of serum CDT as a measure of alcohol consumption in
      patients with HH may be compromised, especially during intensive iron depletion.

PMID- 7803258
TI  - Human cytomegalovirus (HCMV) infection in paediatric patients given allogeneic
      bone marrow transplantation: role of early antiviral treatment for HCMV
      antigenaemia on patients' outcome.
AB  - In a prospective study, we evaluated the role of early treatment with ganciclovir
      of human cytomegalovirus (HCMV) pp65-antigenaemia, as well as the risk factors
      related to the infection in 48 paediatric patients given an allogeneic bone
      marrow transplantation (BMT). HCMV infection occurred in 24 children, the overall
      actuarial risk of infection at 120 d being 51%. Development of acute graft-versus
      host disease (GVHD), steroid therapy and serological status of both recipient and
      donor were the most powerful predictors of HCMV infection, none of the six
      seronegative patient/donor pairs developing HCMV infection. Considering only the
      seropositive recipients and patients given a seropositive marrow (42 cases), the
      actuarial risk of developing HCMV antigenaemia in patients with acute GVHD was
      76% v 27% in those with or without GVHD (P < 0.005) and 79% v 15% respectively in
      patients who did or did not receive steroid therapy (P < 0.001). HCMV disease
      developed in 5/24 children with pp65-antigenaemia, which was detected before
      diagnosis in all cases but one. All patients with pp65-positive cells were
      treated with ganciclovir at a dose of 5 mg/kg twice daily for 14 d. In patients
      without acute GVHD no maintenance therapy was administered, whereas children with
      active acute GVHD were given additional therapy with ganciclovir at a dose of 5
      mg/kg/d for 14 d. Ganciclovir produced complete clearing of viraemia and
      antigenaemia, with some patients presenting recurrences of antigenaemia, which
      were treated according to the above-mentioned schedule. Likewise, HCMV disease
      completely resolved after treatment with ganciclovir and no patients died from
      HCMV-related interstitial pneumonia. Our results suggest that an early short-term
      therapy with ganciclovir after demonstration of antigenaemia can be effective in
      reducing or abolishing HCMV-related mortality. This approach eliminates the use
      of ganciclovir in patients not presenting HCMV reactivation and therefore not
      benefiting from therapy. The administration of ganciclovir limited to the period
      needed to obtain antigenaemia clearance could also have the advantage of reducing
      myelotoxicity.

PMID- 7803259
TI  - Treatment of advanced acute leukaemia with allogeneic bone marrow transplantation
      from unrelated donors.
AB  - Bone marrow transplantation from a histocompatible sibling donor may produce
      complete remission in patients with induction failure or relapsed acute
      leukaemia. Through the National Marrow Donor Program, histocompatible bone marrow
      from unrelated donors has become available for high-risk patients. In this study
      we analyse the results of matched unrelated bone marrow transplant in 55 patients
      with highly advanced acute myelogenous and acute lymphoblastic leukaemia. 28
      patients with advanced acute lymphoblastic leukaemia and 27 patients with
      advanced acute myelogenous leukaemia, age 2-51, were treated with high-dose
      chemoradiotherapy and transplantation of 6/6 HLA matched (n = 46) or one antigen
      mismatched (n = 9) unrelated donor bone marrow. After a median follow-up of 36
      months, 13 patients remain alive 17-74 months after transplant for a 2-year
      actuarial disease-free and overall survival of 23 +/- 12% (median disease-free
      survival 3.5 months). The actuarial risk of relapse is 24 +/- 16% at 1 year.
      Moderate to severe graft-versus-host disease occurred in 27/47 evaluable patients
      (57%). Significant prognostic factors for poor leukaemia-free survival include
      age > 21, abnormal karyotype, and active leukaemia at the time of transplant.
      Other pretreatment characteristics such as gender or type of leukaemia were not
      significant prognostic factors. Our results show that matched unrelated bone
      marrow transplant for patients with advanced acute leukaemia may provide long
      term leukaemia-free survival, but transplant-related complications produce a
      significant impact on survival with older age and adverse disease characteristics
      predicting for poor prognosis.

PMID- 7803260
TI  - Influence of donor lymphocytes on the incidence of primary graft failure after
      allogeneic bone marrow transplantation in a murine model.
AB  - We used a murine model to determine the impact of donor lymphocyte subsets on the
      incidence of primary marrow graft failure after transplantation of lymphocyte
      depleted bone marrow. After lethal irradiation with 7.5 Gy, Balb/c mice received
      1 x 10(5) to 4 x 10(7) GvH-nonreactive (C57 x Balb)F1 or GvH-reactive C57Bl/6
      marrow cells. Pretreatment with anti-Thy-1.2, anti-CD4/CD8, anti-asialo-GM1 or L
      leucyl-L-leucine methyl ester (Leu-Leu-OMe) was employed to eliminate T
      lymphocytes and/or natural killer cells. Primary graft failure was defined as
      death with neutrophils < 0.5 x 10(9)/l. To assess long-term chimaerism, the
      percentage of H-2b-positive spleen cells was determined. Pretreatment with anti
      Thy-1.2, anti-CD4/CD8 or Leu-Leu-OMe successfully eliminated GvHR-induced
      mortality. Graft failure rates gradually declined from 88% after transplantation
      of 1 x 10(5) cells to 0% after transplantation of 4 x 10(7) C57Bl/6 cells. The
      incidence of graft failure, however, was not altered by T-cell depletion,
      provided that the unspecific loss of marrow cells was compensated for. After
      transplantation of GvH-nonreactive (C57 x Balb)F1 bone marrow, neither ex-vivo
      treatment with anti-Thy-1.2 and anti-asialo GM1 nor addition of 1 x 10(7) donor
      thymocytes to the allograft significantly influenced engraftment. The data
      obtained in our animal model suggest that the total number of marrow cells is of
      critical importance for successful marrow engraftment and not the presence or
      absence of T cells, NK cells or GvHR.

PMID- 7803261
TI  - Estimated 8-year survival of more than 40% in a population-based study of 79
      adult patients with acute lymphoblastic leukaemia.
AB  - We report 11 years experience with a modified version of a chemotherapy programme
      in use at the MRC Leukaemia Unit from 1982 to 1984, supplemented by allogeneic
      bone marrow transplantation in first relapse or second or later remission from
      1985. 79 consecutive patients aged 15-60 years with newly diagnosed acute
      lymphoblastic leukaemia (ALL) were given induction chemotherapy. This included a
      standard DAT course (daunorubicin, cytarabine and thioguanine) applied as in
      acute myelogenous leukaemia approximately midway in the induction programme. A 3
      year rotating maintenance programme consisted of combinations of cytotoxic drugs
      used in the induction therapy. CNS prophylaxis did not include CNS irradiation.
      Allogeneic BMT was not performed in first remission. The overall complete
      remission (CR) rate was 82% (65/79). 26 patients relapsed (seven first in the
      CNS). Seven patients underwent allogeneic BMT of whom six are alive and well with
      a mean observation time of 32 months (range 4-99 months) after transplantation.
      Three patients died in first CR. Estimated 5- and 8-year overall survival was 51%
      (95% confidence interval (CI) 39-63) and 47% (CI 33-61). For patients who reached
      CR, the corresponding figures were 63% (CI 50-76) and 57% (CI 41-73). Estimated
      disease-free survival in the remitters was 54% (CI 40-68) at 5 years and 44% (CI
      28-60) at 8 years. Patient age below 25 years and white cell count below 15 x
      10(9)/l at presentation were both found to improve the chance of overall
      survival.

PMID- 7803262
TI  - Transforming growth factor-beta and megakaryocytes in the pathogenesis of
      idiopathic myelofibrosis.
AB  - Although the disease is well described, the pathogenesis of bone marrow fibrosis
      in idiopathic myelofibrosis still remains unclear. We previously reported
      elevated intraplatelet transforming growth factor-beta (TGF-beta) levels in
      patients with this myeloproliferative disorder, compared with healthy subjects.
      Here, in a series of 16 patients, we show that TGF-beta expression is also
      increased in patients' peripheral blood mononuclear cells (PBMC): (i) at the mRNA
      level analysed by Northern blot hybridization and/or reverse transcription
      polymerase chain reaction (RT-PCR); (ii) and/or at the secreted peptide level as
      evaluated in conditioned media from patients' mononuclear cells by a growth
      inhibition assay on CC164 cells. By immunostaining with a polyclonal anti-TGF
      beta 1 antibody, TGF-beta was localized in morphologically heterogenous cells;
      these cells were characterized as megakaryocytes by labelling with a gpIIbIIIa
      monoclonal antibody. Thus we provide evidence that both TGF-beta and
      megakaryocytes are linked in the pathogenesis of idiopathic myelofibrosis.

PMID- 7803263
TI  - Acute lymphocytic leukaemia in the elderly: characteristics and outcome with the
      vincristine-adriamycin-dexamethasone (VAD) regimen.
AB  - To analyse the pretreatment characteristics, response to therapy, and overall
      prognosis of elderly patients with acute lymphocytic leukaemia (ALL), 268
      consecutive adults with newly-diagnosed ALL who received the vincristine
      adriamycin-dexamethasone (VAD) regimens were reviewed. Pretreatment
      characteristics, response to VAD therapy, and overall outcome were analysed in
      patients 60 years or older, and compared to younger patients. Fifty-two patients
      (19%) were 60 years or older. Compared with younger patients, elderly patients
      with ALL had a significantly worse performance status at presentation (P <
      0.001); higher incidences of FAB L2 morphology (P = 0.03), thrombocytopenia (P <
      0.01), hypoalbuminaemia (P < 0.001) and renal dysfunction (P = 0.03); and trends
      for worse anaemia (P = 0.06) and a higher rate of myeloid markers positivity (P =
      0.06). With VAD induction therapy, elderly patients had a lower CR rate than
      younger patients following two induction courses (CR rate 58% v 82%; P < 0.01),
      and overall (CR rates 65% v 90%; P < 0.01). The response rate to VAD
      chemotherapy, however, appeared superior to the 30-35% CR rates reported from
      other series in elderly ALL patients. The lower CR rate was due to both higher
      induction mortality (P = 0.02) and more resistant disease (P < 0.01). The long
      term CR rate was 20% in elderly patients achieving CR, but the overall survival
      was poor (< 10% at 3 years). There were strong associations between older age and
      other poor prognostic features. However, multivariate analyses identified older
      age to be an independent poor prognostic factor for response to chemotherapy. In
      summary, elderly patients with ALL have an appreciable CR rate with the VAD
      regimens. Patients achieving CR may have durable remissions. The myelosuppression
      associated mortality in both remission induction and maintenance may be reduced
      with the addition of growth factors in both treatment phases, and by using
      standard maintenance therapy without consolidation-intensification phases.

PMID- 7803264
TI  - Acute lymphoblastic leukaemia in adults: the case for a strategic shift in study
      approach.
AB  - After 20 years of frantic chemotherapeutic activity, all concerned with adult ALL
      are now resigned to the fact that only some 20% of the overall adult cases are
      biologically similar to childhood ALL, and the majority of these are in the
      adolescent age groups. It is evident that as much effort as possible must be made
      to dissect out such chemocurable patients from the bulk of patients with adult
      ALL so that they might obtain cure with conventional chemotherapy, thus avoiding
      early transplantation or unnecessary intensification. In such a rare disease,
      unless we organize nationally, and look at population-based studies linked to
      phase III or phase II studies where appropriate, we are destined not to develop
      appropriate strategies for treatment of this disease for a long time to come.

PMID- 7803266
TI  - The effects of IL-1 and IL-4 on the Epo-independent erythroid progenitor in
      polycythaemia vera.
AB  - Human recombinant interleukin-1 (IL-1) was studied for its effects on the
      erythroid progenitors from normal subjects and from patients with polycythaemia
      vera (PV). No supportive effect of IL-1 was noticed on the normal, erythropoietin
      (Epo) dependent, erythroid burst-forming unit (BFU-E) using peripheral blood or
      bone marrow. In contrast, the Epo-independent BFU-E from peripheral blood of PV
      patients could be stimulated significantly. This enhancing effect of IL-1 was not
      only observed with unsorted but also with sorted CD34+ cells. In addition, it was
      shown that IL-1 indirectly stimulated the Epo-independent BFU-E because anti-GM
      CSF could abrogate the supportive effects of IL-1. In contrast to the Epo
      independent BFU-E, the Epo-dependent erythroid colony formation from PV patients
      could not be augmented by IL-1. Finally, we studied the effects of IL-4 on the
      Epo-independent BFU-E, because IL-4 can affect the erythroid colony formation and
      modulate the effects of IL-1. IL-4 suppressed the Epo-independent BFU-E. This
      effect could be counteracted by the addition of IL-1 to the culture medium.
      However, the suppressive effect of IL-4 was not related to a decline in
      spontaneous release of IL-1, because an anti-IL-1 antibody did not modify the
      spontaneous erythroid colony formation. These data indicate that IL-1 and IL-4
      exert separate influences on the Epo-independent erythroid colony formation in
      PV.

PMID- 7803265
TI  - Established IL-2-dependent double-negative (CD4- CD8-) TCR alpha beta/CD3+ ATL
      cells: induction of CD4 expression.
AB  - We established IL-2-dependent T cells from an adult T-cell leukaemia (ATL)
      patient whose leukaemic cells changed from CD4 single-positive in the initial
      phase to double-negative (CD4- CD8-) at the time of exacerbation. The cells
      termed SO-4 were of ATL cell origin and showed the double-negative TCR alpha
      beta/CD3+ T-cell phenotype. SO-4 cells acquired CD4 antigen expression following
      stimulation with concanavalin A (ConA) or immobilized anti-CD3 antibody. The
      induction was inhibited by herbimycin A, an inhibitor of protein tyrosine kinase
      (PTK) activity. No CD4 mRNA was detectable in unstimulated SO-4 cells but a 3.0
      kb signal specific for CD4 mRNA was detected after stimulation. These findings
      indicate that SO-4 cells return to their original phenotype (CD4 single-positive)
      by stimulation involving PTK. The results indicate that there is a pathway of
      phenotypic cycling between CD4 single-positive and double-negative T cells.

PMID- 7803267
TI  - All-trans retinoic acid promotes a differential regulation of adhesion molecules
      on acute myeloid leukaemia blast cells.
AB  - In the present study we investigated the membrane expression of selectin ligands
      (CD15/Le(x), CDw65/VIM2, CD15s/sLe(x), beta 2 integrins (CD11a/LFA-1, CD11b/Mac
      1) and CD45 phosphatase isoforms (CD45RA, CD45O) on leukaemic cells from 28
      patients with acute myeloid malignancies cultured with and without all-trans
      retinoic acid (ATRA). Within each adhesion system. ATRA was able to
      differentially regulate distinct molecules. Furthermore, it was able to exert
      effects specific for acute promyelocytic leukaemia (APL) blast cells, as well as
      to induce a series of non-cytotype-restricted phenotypic changes. An impressive
      feature of ATRA induction was a simultaneous increase in the expression of CD15,
      CDw65 and CD11b on leukaemic promyelocytes. The sialylated antigen CD15s,
      however, showed results independent from the other two carbohydrates (CD15 and
      CDw65), suggesting a differential enzymatic regulation within the selectin
      ligands system. In spite of the well-recognized expression of CD11a throughout
      all stages of normal myeloid differentiation, APL blast cells were found to
      virtually lack LFA-1 expression. Moreover, ATRA was unable to promote an up
      regulation of this antigen in APL, while inducing a frequent down-modulation in
      non-APL cases constitutively expressing this antigen. In APL cases ATRA generated
      an asynchronous phenotype (CD15+, CDw65+, CD11b+, CD11a-), undetectable on
      normally maturing myeloid cells, but consistent with the concept that incomplete
      differentiation, in terms of surface molecule expression, can be sufficient to
      obtain therapeutic results.

PMID- 7803268
TI  - Recombinant human immunodeficiency virus type-1 (HIV-1) Tat protein sequentially
      up-regulates IL-6 and TGF-beta 1 mRNA expression and protein synthesis in
      peripheral blood monocytes.
AB  - In this study we evaluated the effect of human immunodeficiency virus type 1 (HIV
      1) recombinant Tat protein on mRNA expression and protein synthesis of two
      inflammatory cytokines-interleukin-6 (IL-6) and transforming growth factor-beta 1
      (TGF-beta 1)-by peripheral blood (PB) monocytes. Whereas maximal levels of IL-6
      protein were recovered in PB monocyte culture supernatants after 24-48 h from the
      addition of 1 micrograms/ml of recombinant Tat, TGF-beta 1 showed a slower and
      progressive increase, reaching maximal levels only after 72-96 h of culture.
      Consistently, the analysis of the steady-state levels of mRNA showed a sharp
      increase of IL-6 mRNA expression after 24h of culture, with a slow decline
      thereafter. On the other hand, TGF-beta 1 mRNA expression showed a slow increase
      only after 72-96 h of culture. Moreover, IL-6 appeared involved in the up
      regulation of TGF-beta 1, because the addition of a neutralizing anti-IL-6
      antibody to Tat-treated PB monocyte cultures significantly reduced the amounts of
      TGF-beta 1 recovered in the culture supernatants after 96 h. The present
      demonstration that HIV-1 Tat protein directly up-regulates IL-6 expression and
      stimulates TGF-beta 1 production both directly and indirectly, through early IL-6
      production, could have important implications in the pathogenesis of HIV-1
      disease.

PMID- 7803269
TI  - Interferon-alpha up-regulates bcl-2 expression and protects B-CLL cells from
      apoptosis in vitro and in vivo.
AB  - The bcl-2 oncoprotein, which is involved in the t(14,18) translocation, protects
      cells against apoptosis. We examined the effects of interferon-alpha (IFN-alpha)
      on bcl-2 protein expression and apoptosis in B-chronic lymphocytic leukaemia (B
      CLL) cells. None of 12 patients with B-CLL examined expressed the t(14,18)
      translocation; however, all these, and seven other patients, expressed
      significant levels of bcl-2 protein. In vitro, IFN-alpha (500 U/ml over 18 h)
      increased bcl-2 expression on CLL cells (to 200 +/- 23% of control MCF, as
      determined by indirect immunofluorescence and flow cytometry, n = 10, P < 0.001).
      All of eight patients who received IFN-alpha (3 megaunits subcutaneously three
      times a week) demonstrated an increase in bcl-2 expression on circulating
      malignant cells. CLL cells undergo apoptotic cell death when cultured in vitro
      (35.6 +/- 10.3% DNA fragmentation after 18 h, n = 10). In the presence of IFN
      alpha, however, DNA fragmentation was reduced to 6.6 +/- 5.8% (n = 10, P <
      0.001). IFN-alpha also protected CLL cells against apoptosis induced by
      hydrocortisone and gamma irradiation (reducing DNA fragmentation from 63.9 +/-
      12.6% to 10.8 +/- 4.5% and from 80 +/- 2.9% to 5.4 +/- 1.6%, respectively, P <
      0.001 for both). The protective effect of IFN-alpha was dose dependent, and
      maintained for up to 24 h. Our data demonstrate that bcl-2 expression and
      apoptosis of CLL cells can be influenced by cytokines. In addition, it seems
      unlikely that the observed clinical responses to IFN-alpha in patients with CLL
      are due to a direct effect on the malignant cells.

PMID- 7803270
TI  - Persistent polyclonal lymphocytosis with binucleated B lymphocytes: a genetic
      predisposition.
AB  - Persistent lymphocytosis is usually associated with a malignant
      lymphoproliferative disease (MLPD). We report six female patients presenting a
      chronic, moderate lymphocytosis of 2-16 years duration with atypical binucleated
      lymphocytes on peripheral blood smears. Further investigation showed a polyclonal
      increase in serum IgM and HLA-DR7 phenotype in all patients. The B cells were
      polyclonal because Southern hybridization of DNA and polymerase chain reaction
      failed to demonstrate a clonal rearrangement of immunoglobulin heavy chain genes.
      Peripheral blood examination showed binucleated lymphocytes in a family member of
      two of the cases; taken together with the association with HLA-DR7 these data
      suggest a genetic predisposition. The identification of this benign syndrome is
      important in order to prevent its misdiagnosis as a MLPD.

PMID- 7803271
TI  - Aplastic anaemia following exposure to 3,4-methylenedioxymethamphetamine
      ('Ecstasy').
AB  - We report two cases of aplastic anaemia following exposure to 'Ecstasy' (MDMA,
      3,4-methylenedioxymethamphetamine). In both cases the aplastic anaemia resolved
      spontaneously 7-9 weeks after presentation. Long-term bone marrow culture study
      of one patient demonstrated complete normalization of haemopoiesis at time of
      haematological recovery, suggesting either that damage to the haemopoietic stem
      cell had been only transient, or that a more mature, committed progenitor cell
      was the target. Because MDMA may have been a factor in the aetiology of the bone
      marrow suppression in these two cases, we recommend close haematological
      monitoring of young adults presenting with toxicity from MDMA, and a detailed
      history of exposure to recreational drugs in all new patients presenting with
      aplastic anaemia.

PMID- 7803272
TI  - Serum erythropoietin and serum transferrin receptor levels in aplastic anaemia.
AB  - Serum erythropoietin (EPO) and soluble transferrin receptor levels were serially
      measured in 74 patients with aplastic anaemia (AA). As control groups we
      investigated healthy controls (n = 24) and patients with iron-deficiency (n = 23)
      or haemolytic anaemia (n = 16). There was a significant negative correlation of
      log EPO on haematocrit both in AA patients and in the anaemic control group.
      However, for the same degree of anaemia, log EPO levels in AA were significantly
      higher than in iron-deficiency or haemolytic anaemia. EPO levels at diagnosis did
      not correlate with severity of aplastic anaemia, nor did they predict outcome
      after immunosuppression. During immunosuppressive treatment of AA with anti
      thymocyte globulin and cyclosporine A, EPO levels were significantly lower
      compared with pre-treatment values without a corresponding change in haematocrit.
      This impaired EPO response to anaemia during immunosuppression might affect
      recovery of erythropoiesis. In AA patients, EPO levels declined with haemopoietic
      recovery. However, compared with normal controls, EPO levels in remission
      patients were still higher with respect to their haematocrit. Results of this
      study argue against the model of a simple feedback regulation of EPO via hypoxic
      anaemia. Our data support the hypothesis that cytokines and the erythropoietic
      progenitor pool are involved in the regulation of EPO production. The results
      illustrate that serial measurements of EPO along with therapeutic interventions
      are necessary to identify patients who might benefit from treatment with
      exogenous recombinant human EPO.

PMID- 7803273
TI  - Red cell membrane protein abnormalities in hereditary spherocytosis in Brazil.
AB  - We studied 14 kindred and nine unrelated patients from southeastern Brazil with
      the typical form of hereditary spherocytosis. Diagnosis was made on the basis of
      clinical features, presence of spherocytes on the peripheral blood smears and an
      abnormal osmotic fragility test. By densitometric tracing of SDS-PAGE stained by
      Coomassie blue, we detected isolated deficiency of spectrin in 39% of our
      patients, combined spectrin and ankyrin deficiency in 13%, and deficiency of band
      3 in 13%. One of our patients presented ankyrin deficiency without spectrin
      reduction. Our data suggest that, despite ethnic differences among the Brazilian
      and European or North-American populations, these biochemical abnormalities in HS
      patients may be similar.

PMID- 7803274
TI  - The differences in quantities of alpha 2- and alpha 1-globin gene variants in
      heterozygotes.
AB  - We have identified through sequencing of amplified DNA the mutations in the alpha
      2- and alpha 1-globin genes in 63 individuals with a heterozygosity for an alpha
      chain abnormal haemoglobin (Hb). Moreover, we developed a reverse
      transcription/polymerase chain reaction (RT/PCR) based procedure for the
      determination of the alpha 2- and alpha 1-mRNA ratio in normal individuals. The
      numbers of alpha 2 and alpha 1 variants were nearly the same. The average
      percentage of the abnormal Hb in heterozygotes with alpha 2 mutations (23.5%) was
      slightly higher than that in heterozygotes with alpha 1 mutations (19.7%) (stable
      Hbs only). These percentages correspond to a ratio of alpha 2 to alpha 1 of 1.19
      to 1 at the protein level. Variations in the number of active alpha-globin genes
      and in the stability of the variants (greatly) affected the percentages of the
      abnormal protein. The average ratio between the alpha 2- and alpha 1-mRNAs in 12
      normal individuals was 2.6-2.75 to 1, about as expected from published data, and
      2.0 to 1 for two persons with an alpha-thalassaemia-2 (alpha-thal-2) (-3.7 kb)
      heterozygosity. The high relative mRNA (alpha 2) level which is about twice the
      relative level of the alpha 2 protein suggests a less efficient translation of
      the alpha 2-mRNA.

PMID- 7803275
TI  - A novel beta-thalassaemia mutation in the 5' untranslated region of the beta
      globin gene.
AB  - A thymidine deletion at position +10 of the 5' untranslated region of the beta
      globin gene was detected in a beta-thalassaemia intermedia patient carrying a
      beta(0)39 stop codon mutation on the other chromosome; this new mutation, +10(
      T), was detected by automated fluorescent DNA sequencing and verified by dot-blot
      allele-specific hybridizations. The +10(-T) mutation is a 'silent carrier', is
      associated with a reduced amount of steady-state beta-globin mRNA, and
      establishes a connection between the 5' untranslated region of the beta-globin
      gene and the regulation of its expression.

PMID- 7803276
TI  - Retrovirus-mediated transfer of the multidrug resistance gene into human
      haemopoietic progenitor cells.
AB  - We report the utilization of cord blood (CB) or bone marrow (BM) derived low
      density or purified CD34+ cells as a target for human multidrug resistance (MDR1)
      gene transfer. Cells were cocultivated for 48 h with an irradiated MDR1
      retroviral producer line. Since some degree of MDR1 gene expression has been
      reported to occur in haemopoietic progenitor cells and in peripheral blood cells,
      efficiency of MDR1 gene transfer was assessed by: (1) Drug selection and culture
      in presence of 50 ng/ml doxorubicin, 10 ng/ml colchicine and 0.85 micrograms/ml
      taxol. In uninfected control, 1-2% of CFU-GM and CFU-GEMM were found to be drug
      resistant, while 14-31% of original clonogenic activity was found after 2 weeks
      of culture of transduced cells. Efficiency of MDR1 transfer was significantly
      enhanced by prestimulation with cytokines, and found to be significantly superior
      in CB-derived compared to BM-derived progenitors. (2) Analysis of MDR1 gene
      expression by evaluating MDR1 mRNA through polymerase chain reaction. MDR1
      expression was very low in cultures of uninfected controls, whereas, after drug
      selection, MDR1 mRNA levels in transduced cells was as high as in the MDR1
      retroviral producer line (positive controls). (3) Flow cytometric analysis of the
      expression of CD34 and P-glycoprotein, the product of the MDR1 gene. After MDR1
      transduction and 2 weeks of culture, membrane expression of P-glycoprotein was
      found on 17-25% of viable CD34+ cells. (4) Cytochemical localization by APAAP
      staining of P-glycoprotein. No specific localization was found in untransduced
      controls, whereas transduced and cultured CB-cells expressed P-glycoprotein on
      plasma and nuclei membrane. In conclusion, MDR1 gene transfer into CB- and BM
      derived progenitor cells seems a feasible and attractive approach to generate a
      drug-resistant haemopoiesis.

PMID- 7803277
TI  - Retroviral-mediated gene transfer into human myeloma cells.
AB  - We have studied retroviral-mediated gene transfer into human myeloma cells. Bone
      marrow cells were obtained from four patients with advanced myeloma, where the
      marrow was heavily infiltrated with myelomatous plasma cells. Myeloma cells were
      isolated by immunomagnetic separation, using the high-affinity B-B4 monoclonal
      antibody. Following separation, cells were transduced with the LN retroviral
      vector, which carries the gene for neomycin phosphotransferase, by incubation in
      cell-free supernatant with or without a growth-factor combination of IL-3, IL-6
      and SCF. After infection, the cells were cultured for 9 d in RPMI-1640 and 10%
      FCS, either in the presence or absence of the neomycin analogue G418.
      Transduction efficiency was 1.5-3.8%, when compared to the number of cells at
      initiation of the culture, and 5.0-50.0% when compared to the number of surviving
      infected cells cultured without G418. The gene transfer rate was similar whether
      or not growth factors were present during the retroviral infection. These
      preclinical data provide evidence that retroviral-mediated gene transfer into
      human myeloma cells is feasible, and form part of the basis for current clinical
      studies of gene marking of bone marrow or peripheral blood progenitor cells
      before autologous stem cell transplantation in multiple myeloma.

PMID- 7803278
TI  - Cytokine response to infection in patients with acute myelogenous leukaemia
      following intensive chemotherapy.
AB  - Septic shock is the major cause of treatment-related death in patients with acute
      myelogenous leukaemia (AML) undergoing intensive chemotherapy. Interleukins (IL)
      1 beta, -6, -8, and tumour necrosis factor alpha (TNF-alpha) have been implicated
      as mediators of septic shock, with circulating leucocytes being considered a
      major source for their release. However, plasma cytokine levels of leucocytopenic
      patients with evolving sepsis have not been studied. We have prospectively
      measured plasma cytokines during chemotherapy-induced leucocytopenia (< 1 x
      10(9)/l) in 50 patients with AML. Cytokine levels in patients with severe sepsis
      (n = 5) or septic shock (n = 8) were compared to those measured in 13 matched
      patients with uncomplicated febrile infections. In evolving septic shock, IL-6,
      IL-8 and TNF-alpha peaked within 48 h of fever onset at levels reported for non
      leucocytopenic patients and distinctively higher than during uncomplicated
      febrile episodes (P < 0.05). Peak concentrations measured within 48 h after onset
      of fever were related to fatal outcome. IL-1 beta was detected in less than 5% of
      all samples. Cytokine concentrations were unrelated to leucocyte counts and
      markers of neutrophil or monocyte activation (elastase and neopterin levels,
      respectively). We conclude that cytokine release associated with evolving septic
      shock in patients with AML does not depend on circulating leucocytes.

PMID- 7803279
TI  - Sequential acquisition of trisomy 8 and N-ras mutation in acute myeloid leukaemia
      demonstrated by analysis of isolated leukaemic colonies.
AB  - Specific chromosomal aberrations and point mutations of the N-ras proto-oncogene
      are characteristic genetic alterations in acute leukaemias. However, the
      relationships between these two different genetic changes are unclear. Here we
      have determined the order of genetic events in a patient with acute myeloid
      leukaemia characterized by trisomy 8 and a point mutation of N-ras at codon 12
      (N12-cys) and codon 61 (N61-his). 30 colonies obtained by in vitro clonogenic
      assay of leukaemic cells from a patient with AML were individually analysed for
      the presence of trisomy 8 and each of two different N-ras mutations by
      fluorescence in situ hybridization (FISH) and the polymerase chain reaction
      (PCR). Trisomy 8 was detected in 25/26 evaluable colonies. 19/26 colonies
      contained the N12-cys mutation. The N61-his mutation was not detected in any of
      the colonies obtained. All the colonies with the N12 cys mutation were also
      trisomic from chromosome 8, whereas 6/25 colonies with trisomy 8 had no N-ras
      mutation. These data suggest that trisomy 8 was acquired before N12 cys mutation
      in the pathogenesis of this leukaemia and that two genetic events can co-operate
      within a single subclone.

PMID- 7803280
TI  - Translocation t(5;12)(q31-q33;p12-p13): a non-random translocation associated
      with a myeloid disorder with eosinophilia.
AB  - A t(5;12)(q33;p13) translocation has been detected in two patients with myeloid
      disorder and eosinophilia. Six other patients with haematological disease with
      eosinophilia with similar translocation have been published previously. The
      existence of a new entity, a myeloproliferative disorder with eosinophilia and
      t(5;12) (q31-q33;p12-p13), is suggested by the results of the present study.

PMID- 7803281
TI  - High expression of the multidrug resistance-associated protein (MRP) in chronic
      and prolymphocytic leukaemia.
AB  - The expression of the multidrug resistance-associated protein (MRP), a new
      glycoprotein involved in drug resistance, was investigated in tumour samples from
      80 patients with chronic B-cell malignancies by a quantitative RNase protection
      assay. In B-cell chronic lymphocytic leukaemia (B-CLL) (n = 32), either treated
      (n = 18) or untreated (n = 14), a high percentage of patients (20/32: 63%) had
      relatively high expression levels of the MRP gene (25U or more). In addition,
      hyperexpression of the MRP gene was demonstrated in 4/10 (40%) untreated patients
      with B-cell prolymphocytic leukaemia (B-PLL). In contrast, low MRP mRNA
      expression levels were detected in hairy cell leukaemia (n = 7), non-Hodgkin's
      lymphoma (n = 13) and multiple myeloma (n = 18). Statistical analysis of MRP
      expression in untreated CLL (mean +/- SD 29.2 +/- 18.5 U) versus treated CLL
      (mean +/- SD 26.7 +/- 13.7 U) did not show significant differences in MRP
      expression between the two groups. Southern blot analysis did not reveal
      amplification of the MRP gene in the leukaemia samples with elevated MRP mRNA
      levels. We conclude that B-PLL and B-CLL frequently display high MRP expression
      and that this hyperexpression is probably due to transcriptional activation
      and/or increased mRNA stability.

PMID- 7803282
TI  - Distinct lysozyme content in different subtypes of acute myeloid leukaemic cells:
      an ultrastructural immunogold study.
AB  - Using an ultrastructural immunogold method, we performed a quantitative study on
      cellular lysozyme (LZ) content in young normal bone marrow cells and in 14 cases
      of acute myeloid leukaemia (AML) of the M2, M3, M4 and M5 types. In five cases of
      M2 we found significantly lower LZ content than in normal promyelocytes and than
      in nine cases of M3, M4 and M5. In M3, M4 and M5 cells a very high LZ content was
      observed whereas the serum LZ activity was high in M4 and M5 and normal in M3.
      The intragranular LZ content was especially high in M5 and in most granules of M4
      cells. The immunogold reaction (IGR) for LZ was also performed in cells
      previously reacted for myeloperoxidase (MPO). In M2 the granules showed definite
      positive MPO reactivity and low LZ density (granulocytic pattern), whereas in M5
      we found high granular LZ content and weak or almost negative MPO activity
      (monocytic pattern). In M4 we found 'granulocytic' and 'monocytic' type of
      granules in the same cell. The IGR for LZ performed in post-embedded M5 cells
      which were previously subjected to phagocytosis of latex particles, showed
      granules that had moved toward the phagosome, releasing LZ without degranulation.
      The above findings and those showing normal serum LZ in M3 despite their high
      cellular LZ content, definitely indicate that only leukaemic M4 and M5 cells
      secrete LZ into their environment, explaining the high serum LZ observed in those
      leukaemias.

PMID- 7803283
TI  - Platelet procoagulant complex assembly in a tissue factor-initiated system.
AB  - The aim of this study was to examine the assembly of the factor IXa/VIIIa (Xase)
      and factor Xa/Va (IIase) complexes on the platelet surface in a system designed
      to mimic tissue factor-initiated coagulation. The experimental system contained
      tissue factor-bearing monocytes, unactivated platelets, and plasma concentrations
      of factors V, VIII, IX, X, prothrombin, tissue factor pathway inhibitor (TFPI),
      antithrombin III (ATIII), and small amounts of factor VIIa. The time courses of
      platelet activation, coagulation factor binding and thrombin generation were
      compared. In this system, thrombin generation by the combination of monocytes and
      platelets was synergistic compared to each cell type alone. Platelet activation
      and thrombin generation were minimal in the absence of prothrombin or factor X.
      After a lag period, platelet activation began, followed by progressive binding of
      factors Va and VIIIa. This was followed by factor IXa and Xa binding and the
      onset of thrombin generation. Unexpectedly, a transient early increase in
      platelet-associated factor IX and X was also seen, that was due to release from
      platelets. The amount of factor IX bound to isolated activated platelets was
      increased by addition of factor VIIIa, or by activation of factor IX to IXa. In
      contrast, factor VIIIa binding was not altered by the presence of factor IX or
      IXa. We conclude that in a tissue factor-initiated system, assembly of the
      procoagulant complexes on the platelet surface begins after platelet activation
      occurs. Platelet activation requires thrombin generation in the vicinity of the
      tissue factor bearing cells. The cofactors Va and VIIIa bind to the platelets and
      facilitate subsequent binding of factors IXa and Xa to form functional
      procoagulant complexes.

PMID- 7803284
TI  - Ultrastructural localization of the small GTP-binding protein Rap1 in human
      platelets and megakaryocytes.
AB  - Several functions have been proposed for Rap1B in human platelets, including the
      regulation of phospholipase (PL) C gamma and Ca2+ ATPase. However, its
      localization is largely unknown. In the present study we have investigated the
      subcellular distribution of Rap1 by immunocytochemical techniques using affinity
      purified polyclonal antibodies raised against residues 121-137 common to the 95%
      homologous Rap1A and Rap1B proteins. By immunofluorescence, a positive labelling
      was obtained on intact resting platelets and was abolished after adsorption of
      the antibodies with the control peptide. Immunoelectron microscopy was then used
      to further define the subcellular localization of Rap1B in platelets and
      megakaryocytes (MK). In resting cells, immunolabelling for Rap1B was associated
      with the plasma membrane, mostly at its inner face, and lined the membrane of the
      open canalicular system (OCS). Some labelling was also found outlining the alpha
      granules, identified as such by a double labelling with an anti-GPIIb-IIIa. On
      thrombasthenic platelets the same localization was observed. When platelets were
      stimulated by thrombin, immunolabelling for Rap1B was redistributed to the zones
      of fusion of the granules with the OCS, and to the plasma membrane with a higher
      concentration on pseudopods. Human MK expressed Rap1 and the staining revealed
      the association of the protein with the demarcation membranes and alpha-granules.
      This study presents a first approach to the localization of a small GTP binding
      protein Rap1B in whole platelets and MK, and shows its association with both the
      plasma and OCS membranes, as well as with the alpha-granule membranes.

PMID- 7803286
TI  - Involvement of eosinophils in acute myeloid leukaemia with monosomy 7
      demonstrated by fluorescence in situ hybridization.
AB  - Monosomy 7 is the commonest monosomy in acute myeloid leukaemia (AML). A patient
      with AML and monosomy 7 was investigated by fluorescence in situ hybridization.
      Monosomy 7 could be demonstrated in the blasts and also in mature eosinophils,
      but apparently not in lymphocytes. Monosomy 7 may occur in a multipotential
      myeloid progenitor cell as part of the multi-step leukaemogenic process.

PMID- 7803285
TI  - Thrombin receptor expression and function in large granular lymphocyte
      proliferative disorders.
AB  - It has recently been shown that peripheral blood NK-cells and a fraction of T
      cells which co-express CD16 and either CD56 or CD57 express the platelet type
      thrombin receptor. Large granular lymphocytes exhibit a T- or NK-cell phenotype,
      and therefore these results raise the possibility that thrombin and its receptor
      may be involved in the biology of large granular lymphocytes in health and
      disease. It is difficult, however, to perform functional studies using normal
      blood as a source of large granular lymphocytes, because the small fraction of
      large granular lymphocytes cannot be separated from other lymphocytes in numbers
      sufficient for most in vitro experiments. Therefore patients with large granular
      lymphocyte proliferative disorders have been screened in order to identify a
      population of cells enriched in large granular lymphocytes that express the
      thrombin receptor. Expression of the receptor was analysed in polyclonal and
      clonal large granular lymphocyte proliferative disorders. Using flow cytometry,
      it was found that the proportion of thrombin receptor positive large granular
      lymphocytes varied from 3% to 86%. Northern analysis indicated a high level of
      expression of mRNA in a clonal expansion of large granular lymphocytes that
      stained positively for the receptor by flow cytometry. Thrombin was found to act
      as a chemotactic stimulus for large granular lymphocytes from a polyclonal
      expansion with high numbers of thrombin receptor positive cells. At an optimal
      concentration of 10(-9) M the chemotactic response to thrombin was roughly
      equivalent to that obtained with the potent chemoattractant 1-oleoyl 2-acetyl
      glycerol. These findings suggest that thrombin may play a role in the recruitment
      of large granular lymphocytes in sites of inflammation.

PMID- 7803287
TI  - Hepatitis C virus infection in patients with non-Hodgkin's lymphoma.
AB  - Hepatitis C virus (HCV), which is both a hepatotropic and a lymphotropic virus,
      has been proposed as a possible causative agent of mixed cryoglobulinaemia. This
      'benign' lymphoproliferative disorder can switch over to a malignant B-cell non
      Hodgkin's lymphoma (NHL). Therefore HCV infection has been investigated in a
      series of 50 unselected Italian patients with B-cell NHL. Antibodies against HCV
      were found in 30% of NHL and HCV viraemia in 32% of cases. HCV-related markers
      were detected in 34% (17/50) of our NHL patients; this prevalence is particularly
      significant when compared with HCV seropositivity in Hodgkin's lymphoma (3%) and
      healthy controls (1.3%).

PMID- 7803288
TI  - IgD monoclonal gammopathy with long-term follow-up.
AB  - The presence of a serum IgD monoclonal protein (M-protein) is usually indicative
      of a malignant plasma cell disorder. However, one case of well-documented benign
      monoclonal gammopathy (BMG) of IgD type has been reported. We describe another
      patient with IgD monoclonal gammopathy of undetermined significance (MGUS) with
      long-term follow-up. In this patient an IgD lambda M-protein was found on routine
      serum electrophoresis. She is alive and has no evidence of multiple myeloma or
      amyloidosis after 8 years of follow-up. Although IgD MGUS is exceedingly rare,
      this case demonstrates that the presence of a serum IgD M-protein is not
      necessarily synonymous with a malignant plasma cell process.

PMID- 7803289
TI  - HCV RNA levels and HIV infection: evidence for a viral interaction in haemophilic
      patients.
AB  - In order to investigate a possible interaction between HIV and HCV infections, we
      compared HCV RNA levels in 29 matched pairs of haemophilic patients seropositive
      for HCV and serodiscordant for HIV. Levels were assayed using the new Chiron
      Quantiplex bDNA assay and were found to be significantly higher in HIV
      seropositive patients. There was no association between HCV RNA and age, duration
      of HCV infection, concentrate usage, markers of HIV progression, or use of
      zidovudine. Our study supports the hypothesis that HIV infection facilitates HCV
      replication and leads to more severe liver damage.

PMID- 7803290
TI  - Aplasia after donor lymphocyte infusion (DLI) for CML in relapse after sex
      mismatched BMT: recovery of donor-type haemopoiesis predicted by non-isotopic in
      situ hybridization (ISH).
AB  - We report a patient with CML in relapse after a sex-mismatch bone marrow
      transplant who was treated with donor lymphocyte infusions and developed severe
      marrow aplasia 3 months later. As cytogenetic analysis at this point was not
      possible because of the very low number of marrow cells available, we used in
      situ hybridization (ISH) for sex chromosomes and the BCR/ABL gene together with
      quantitative PCR to monitor the patient's response. The results suggest that
      recovering haemopoiesis was derived from donor cells and contributed to the
      decision not to transfuse donor marrow cells on a second occasion.

PMID- 7803291
TI  - Infection of donor lymphocytes with human T lymphotrophic virus type 1 (HTLV-I)
      following allogeneic bone marrow transplantation for HTLV-I positive adult T-cell
      leukaemia.
AB  - Human T lymphotrophic virus type 1 (HTLV-I) associated leukaemia has a poor
      prognosis even with chemotherapy. We describe a patient with adult T-cell
      leukaemia treated with allogeneic bone marrow transplantation from an HTLV-I
      negative identical sibling donor. During follow-up after bone marrow
      transplantation, HTLV-I could be repeatedly isolated inspite of anti-viral
      prophylaxis. The patient died of an acute encephalitis and HTLV-I could be
      detected in autopsy material from the brain. By a PCR-based technique using short
      tandem repeats (STRs) it was shown that the patient's haemopoiesis was of donor
      origin. This shows the infection of donor cells in vivo by an aetiological agent
      which has been implicated in the leukaemogenic process for adult T-cell
      leukaemia.

PMID- 7803292
TI  - Long-term culture and molecular biological studies highlight differences in
      relative BCR-ABL expression levels in the peripheral blood and bone marrow of a
      patient with chronic granulocytic leukaemia.
AB  - A patient with accelerating Ph+ve chronic granulocytic leukaemia (CGL) was
      considered for autologous BMT using marrow 'purged' by 4 weeks long-term culture
      (LTC). Efficacy of purging was determined using reverse transcriptase PCR for BCR
      ABL mRNA transcripts b2a2 and b3a2. Peripheral blood and bone marrow were
      compared. Three observations emerged: (i) the initial b2a2:b3a2 ratios for
      unmanipulated blood and marrow were different with values of 9:1 and 2:1
      respectively; (ii) both transcripts were successfully 'purged' with LTC of blood
      but not marrow; and (iii) LTC of marrow caused a transient increase in relative
      levels of b3a2 mRNA and a corresponding reduction in the b2a2 signal. This is the
      first case where such differences have been demonstrated in association with LTC.

PMID- 7803293
TI  - Complement receptor type 1 (CR1) deficiency on neutrophils in myelodysplastic
      syndrome.
AB  - We present a patient with myelodysplastic syndromes (MDS) whose neutrophils
      exhibited defective expression of complement receptor type 1 (CR1). A 73-year-old
      man was admitted with an evolution of MDS from RA into RAEBT according to the FAB
      classification of MDS. The neutrophil alkaline phosphatase (NAP) score was zero.
      The surface expression of membrane effector molecules on neutrophils was
      determined by indirect immunofluorescence using flow cytometry and monoclonal
      antibodies. The expression of CR1 on neutrophils as identified by staining with
      CD35 was defective in the patient, and the expression of other complement
      receptors (CR3 and CR4), Fc receptors and adhesion molecules was normal. CR1
      deficiency and defective NAP score on neutrophils in the patient might account
      for impairment of common storage pool, presumably novel intracellular secretory
      vesicles.

PMID- 7803294
TI  - Location and PCR-based detection of three polymorphisms of the human erythrocyte
      beta-spectrin gene (SPTB).
AB  - Defects of beta spectrin, a structural protein of the erythrocyte membrane
      skeleton, have been identified in many cases of inherited disorders of red blood
      cell shape such as hereditary elliptocytosis and spherocytosis. To aid in genetic
      analyses of families with these disorders, the locations of three beta-spectrin
      gene (SPTB) polymorphisms were mapped and PCR-based assays designed for their
      identification. Using these PCR-based assays, the frequencies of these
      polymorphisms were determined in two populations.

PMID- 7803295
TI  - Over-expression of the MDM2 gene is found in some cases of haematological
      malignancies.
AB  - We looked for MDM2 gene amplification and over-expression by Southern and
      Northern blot analysis in 135 and 66 cases of haematological malignancies,
      including ALL, AML, CML in chronic phase, CLL, MDS, PLL, non-Hodgkin's lymphoma
      (NHL) and myeloma. No amplification of the gene was found. An over-expression of
      MDM2 RNA was seen in 9/66 (14%) patients tested, including 3/9 ALL, 3/24 AML, 2/4
      myelomas, 1/1 PLL, but 0/2 CML, 0/2 NHL and 0/21 MDS. None of the patients over
      expressing MDM2 had modifications of P53 gene transcript or p53 mutations. Most
      of the patients over-expressing MDM2 gene had poor prognostic features (including
      'unfavourable' cytogenetic abnormalities), poor response to chemotherapy and
      short survival. Our findings suggest that over-expression of MDM2 is seen in a
      relatively small number of haematological malignancies, and is associated with
      poor prognosis.

PMID- 7803296
TI  - CD30-positive lymphoma in human T-cell leukaemia virus type 1 carrier without
      monoclonal integration of HTLV-1.
AB  - CD30, Ki-1 antigen, an activated T-cell antigen, is a member of the nerve growth
      factor receptor family. This antigen is expressed on the lymphoma cells of some
      adult T-cell leukaemia/lymphoma (ATL/L) patients and some patients with Epstein
      Barr virus infection. CD30-positive large cell cutaneous T-cell lymphomas
      occasionally integrate a defective HTLV-1 provirus. We describe here an HTLV-1
      carrier who developed Ki-1 lymphoma with no evidence of monoclonal integration of
      the HTLV-1 proviral sequence.

PMID- 7803297
TI  - Cytosine arabinoside (Ara-C) plus alpha-interferon (alpha IFN) determine
      prolonged complete remissions in patients with aggressive non-Hodgkin's lymphoma
      partially responsive to first-line doxorubicin-containing regimens.
AB  - Ten patients with aggressive NHL who failed to achieve a complete remission with
      first-line chemotherapy were treated with Ara-C and alpha IFN. Ara-C was
      administered subcutaneously at 100 mg on day 1, 150 mg on day 2 and 200 mg on
      days 3, 4 and 5 of a 28 d cycle; alpha IFN was given at 3 million International
      Units three times a week and continued for 2 years in CR patients. Six CR were
      attained with a median duration of 36+ months. Toxicity was mild. A new approach
      to second-line therapy for aggressive NHL is proposed.

PMID- 7803298
TI  - Beta 2 glycoprotein-I antigen is increased in primary hyperlipidaemia.
AB  - In order to determine whether elevated levels of beta 2 glycoprotein-I (beta
      2GPI) are associated with increased plasma lipids, we measured plasma beta 2GPI
      antigen levels in 47 patients with primary hyperlipidaemia (20 severe
      hypercholesterolaemia, nine severe hypertriglyceridaemia, and 18 mixed
      hyperlipidaemia) and 34 normal healthy subjects. Mean beta 2GPI levels were
      significantly increased in each patient group (302.3, 272.9 and 299.1 mg/l,
      respectively) compared to controls (199.6 mg/l) (P < 0.01). Significant
      correlations were demonstrated between beta 2GPI levels and triglyceride and
      total cholesterol levels in the control group (r = 0.387, r = 0.559; P < 0.05),
      but were not observed in all patient groups. These results indicate that beta
      2GPI is increased in hyperlipidaemia and that its distribution between plasma
      lipid fractions is perturbed. Plasma lipid levels should therefore be considered
      when interpreting results of beta 2GPI antigen assays.

PMID- 7803299
TI  - PML-RAR alpha PCR positivity in the bone marrow of patients with APL precedes
      haematological relapse by 2-3 months.
AB  - We report the results of serial tests in three patients with hyperleucocytotic
      AML M3 by haematological methods, coagulation assays and PCR analyses following
      treatment with ATRA and chemotherapy. All three patients became PCR negative in
      bone marrow and peripheral blood (sensitivity level 1 in 10(5) cells) after one
      cycle of ATRA + chemotherapy. However, they relapsed haematologically 6-9 months
      after achieving complete haematological remission. The haematological relapse was
      preceded by PCR positivity in the bone marrow by 3 months. Platelet counts
      decreased already during CHR, but dropped below normal levels only at the time of
      relapse. Coagulation parameters were not helpful for early prediction of relapse.
      Our results demonstrate that PCR analysis in the bone marrow is the best way to
      monitor patients with APL. However, in hyperleucocytotic patients, PCR negativity
      does not seem to indicate long-term remission.

PMID- 7803300
TI  - Chronic granulocytic leukaemia presenting with an extramedullary T lymphoblastic
      crisis.
AB  - A 33-year-old man presented with hepatosplenomegaly and lymphadenopathy. Bone
      marrow findings were consistent with Philadelphia-positive accelerated-phase
      chronic granulocytic leukaemia (CGL). Lymph node histology and
      immunhistochemistry were diagnostic of T lymphoblastic lymphoma. Molecular
      studies on lymph node DNA identified rearrangement within the major breakpoint
      cluster region (M-bcr), indicating a common clonal origin of CGL and the T
      lymphoblastic lymphoma. We report the second case where extramedullary T
      lymphoblastic crisis was the presenting feature of CGL.

PMID- 7803301
TI  - A deletional frameshift mutation in spectrin beta-gene associated with hereditary
      elliptocytosis in spectrin Napoli.
AB  - We studied a clinically manifest, dominantly transmitted elliptocytosis in an
      Italian family. We found a new spectrin variant, designated spectrin Napoli. Its
      beta-chain was truncated in its C-terminal region (apparent MW 216 kD). It
      displayed a low expression level (15%). There was a 8 nt deletion: CTTTTGAGAAGT-
      >CTGT (nt 6255-6262), starting after codon 2053. This deletion was followed by a
      54 nt (18 amino acids) missense sequence and terminated by the TGA triplet which
      normally overlaps codons 2074 and 2075 (CTTGAG). The overall length of the
      mutated beta-chain was comparable to that found in spectrin Nice, spectrin Tokyo
      and spectrin Tandil, which are other variants with truncated beta-chains;
      however, a distinct nonsense codon was used in spectrin Napoli.

PMID- 7803303
TI  - Measurement of MCV.

PMID- 7803302
TI  - The kinetics of colony formation by CFU-GM in vitro.
AB  - Video-recordings of whole normal bone marrow granulocyte-macrophage colony (CFU
      GM) cultures were made after 7, 14 and 21 d. Retrospective viewing of the tapes
      allowed the relationships to each other of the colonies scored on the three
      different occasions to be documented. The results show that, according to our
      scoring criteria, there is very little overlap between the numbers of colonies
      scored on days 7, 14 and 21. Moreover, only about 10% of the progenitors in a
      sample form day 21 colonies. The remaining progenitors form colonies earlier in
      the culture period and either disappear before day 21 or remain small.

PMID- 7803304
TI  - Neuroblastoma rosettes in aspirated bone marrow.

PMID- 7803305
TI  - Incidence of postoperative epilepsy in children following subfrontal craniotomy
      for tumor.
AB  - Thirty-one children who underwent 36 subfrontal craniotomies were retrospectively
      studied to determine the incidence of postoperative epilepsy and the
      effectiveness of antiepileptic drugs for seizure prophylaxis. The incidence of
      postoperative epilepsy following a subfrontal craniotomy did not exceed 12% when
      examined at various time periods during a 3-year postoperative course.
      Antiepileptic drugs were not warranted to reduce the incidence of postoperative
      seizures after the 1-month postoperative period and should not be used for long
      term prophylactic therapy in children following a subfrontal craniotomy.

PMID- 7803306
TI  - Depressed skull fractures in children secondary to skull clamp fixation devices.
AB  - The use of external skull fixation devices (skull clamps) is a common practice in
      neurosurgery. The insertion of pins into the skull is usually routine and
      uneventful in adult patients. However, the safety of skull clamp fixation devices
      in children is not reported. We have examined our complications over the past 6
      years, and have encountered 5 children with depressed skull fractures secondary
      to application of a skull clamp fixation device. There were 3 boys and 2 girls
      with ages ranging from 3 to 8 years (mean 5.8 years). Two patients had brainstem
      gliomas, 2 patients had hypothalamic gliomas and 1 patient had a medulloblastoma.
      Four of the children required separate cranial procedures for exploration and
      elevation of the depressed fractures. There were no sequelae associated with the
      depressed fractures. We conclude that skull clamp fixation devices are safe, but
      should be used with caution in the pediatric patient. In addition, we present
      several modifications of existing skull clamps which may decrease the risk of
      depressed skull fractures.

PMID- 7803307
TI  - Experience with telemetric pressure measurements in shunt systems. 1981.

PMID- 7803308
TI  - West syndrome associated with porencephaly.
AB  - A 3-year-old boy with West syndrome who was shown to have a cystic lesion on
      magnetic resonance imagings underwent surgical treatment. He had been initially
      managed with several antiepileptic drugs, but abnormalities on
      electroencephalography (EEG) persisted. Histological examination of the cystic
      wall obtained during surgery suggested porencephaly. Two years and 2 months later
      the child remained seizure-free and his EEG remarkably improved.

PMID- 7803309
TI  - Cerebrospinal fluid shunt infection by Neisseria sicca.
AB  - Neisseria sicca is considered to be a nonpathogenic oral saprophyte. Presented
      here is an unusual case of cerebrospinal fluid (CSF) shunt infection by N. sicca.
      Although medical management of the common community-acquired meningitides,
      including infection by Neisseria meningitidis, is often successful in patients
      with CSF shunts, removal and replacement of the infected shunt was necessary in
      this case.

PMID- 7803310
TI  - Gastric perforation due to ventriculo-peritoneal shunt.
AB  - Gastric perforation is a complication that can arise from ventriculo-peritoneal
      (VP) shunting. Careful examination of a newborn girl admitted to our department
      revealed several neurological problems. A VP shunt was inserted under direct
      visualization, leaving 20 cm of the catheter in the peritoneal cavity. The infant
      was discharged 6 days after surgery and readmitted 4 months later due to
      increasing head circumference and severe malnutrition. Physical examination
      revealed a soft abdomen, normal peristalsis, and no signs of peritoneal
      irritation. The patient was submitted to exploratory surgery, which showed that
      the catheter had penetrated about 6 cm into the stomach. The VP shunt was removed
      and replaced by a left ventriculo-atrial system. The patient evolved well and was
      discharged 5 days later. Probable causes of the perforation are discussed in this
      paper.

PMID- 7803311
TI  - Infantile meningioma.
AB  - Childhood meningiomas are unusual, and meningiomas in patients less than 1 year
      of age are exceedingly rare. We report a case of a meningioma with malignant
      histologic features in a 6-month-old child who has had an excellent postoperative
      course. The pathologic features in relation to prognosis, as well as the magnetic
      resonance imaging characteristics of the case are presented. The literature is
      reviewed and implications for therapeutic management are discussed.

PMID- 7803312
TI  - Intracerebral hemorrhage after evacuation of a subdural hematoma in an infant.
AB  - Intracerebral hematomas following evacuation of a subdural hematoma have been
      described in adults resulting from sudden decompression during the drainage of
      the hematoma. In infants an open fontanelle and patent sutures are expected to
      offer protection against sudden decompression. We report the occurrence of
      intracerebral hematoma in an infant following evacuation of a subdural hematoma.
      The multiplicity and centripetal spread of the postoperative hematomas suggested
      that they had resulted from sudden decompression.

PMID- 7803313
TI  - On psychoanalysis and non-linear dynamics: the paradigm of bifurcation.
AB  - Some of Freud's main theoretical conceptualizations drew on metaphors from 19th
      century physics. However, though the physics of Freud's era was based on
      deterministic Newtonian mechanics and equilibrium thermodynamics, his
      descriptions of the dynamics of instincts, therapeutic change, and even
      transference, were far beyond this model. Freud's dynamic description of psychic
      development evokes contemporary theories of irreversible, far-from-equilibrium
      thermodynamics and non-linear dynamics. The present paper focuses on bifurcation
      theory, which offers a paradigm for the investigation of unpredictable but
      deterministic phenomena; this paradigm sheds a retroactive light on the classical
      psychoanalytical conceptualizations of complemental series, repetition
      compulsion, transference and cure.

PMID- 7803314
TI  - Psychotherapy--delayed.
AB  - The problem of the patient who presents repeatedly in distress, wanting help, is
      addressed with reference to one such patient. Paradoxically, by an admission that
      the patient could not be treated, treatment eventually became possible.

PMID- 7803315
TI  - Self-evaluation of psychotherapeutic competence.
AB  - The authors investigated the process of change of self-evaluation of therapeutic
      competence in psychotherapists enrolled in a postgraduate training programme of
      psychotherapy. An analysis of the relationships between self-evaluated
      therapeutic skills and level or stage of formal training was performed. The
      results of this study suggest that a higher level of self-evaluated therapeutic
      skill among applicants was followed by a decline in self-evaluation as the
      training progressed, and a gradual increase in self-evaluation towards the end of
      formal training. The findings reveal a curvilinear pattern of change which
      suggests specific internal cognitive/emotional processes leading to the formation
      of a professional self-image as a psychotherapist.

PMID- 7803316
TI  - Avoidant attachment as a risk factor for health.
AB  - A style of coping with stress is described which has been observed in cancer
      patients and in highly dependent, insecurely attached individuals. This coping
      style includes the suppression of negative emotions and avoidance of support
      seeking. It is suggested that this pattern of responses is potentially
      dysfunctional insofar as it tends to perpetuate distress and may increase
      vulnerability to a broad range of illnesses. These considerations provide the
      basis for a provisional conceptual model, which links avoidant attachment style
      to the regulation of negative affect and to symptoms of psychological and
      physical ill-health. This is tested on a sample of young adults under stress and
      predictions from the model are largely supported.

PMID- 7803317
TI  - Belief in demons and exorcism in psychiatric patients in Switzerland.
AB  - Belief in demons as the cause of mental health problems is a well-known
      phenomenon in many cultures of the world. However, there is little literature on
      this phenomenon in Protestant subcultures of the West. The author conducted a
      systematic investigation of the prevalence of this attribution in 343 mainly
      Protestant out-patients of a psychiatric clinic in Switzerland, who described
      themselves as religious. Of these, 129 (37.6 per cent) believed in the possible
      causation of their problems through the influence of evil spirits, labelling this
      as 'occult bondage' or 'possession'. One hundred and four patients (30.3 per
      cent) sought help through ritual 'prayers for deliverance' and exorcism.
      Prevalence of such practices was significantly related to diagnosis (p < .01) and
      to church affiliation (p < .005). Patients in charismatic free churches suffering
      from anxiety disorders and schizophrenia reported the highest rate of exorcistic
      rituals (70 per cent), and patients with adjustment disorders from traditional
      state churches the lowest (14 per cent). The various forms and functions of these
      healing rituals are described. Although many patients subjectively experienced
      the rituals as positive, outcome in psychiatric symptomatology was not improved.
      Negative outcome, such as psychotic decompensation, is associated with the
      exclusion of medical treatment and coercive forms of exorcism.

PMID- 7803318
TI  - Cognitive behavioural therapy for drug-resistant psychosis.
AB  - A small controlled trial of cognitive behaviour therapy for drug-resistant
      psychosis is reported. The study was designed as a pilot study for a future
      larger and longer randomized controlled trial. The therapy was offered to
      patients with a diagnosis of schizophrenia or schizo-affective psychosis who
      presented unremitting positive symptoms. An average of 16 sessions were delivered
      over a six-month period. The results of this pilot study are promising. Rates of
      engagement in therapy were high. The treatment group also improved significantly
      on a number of key symptom measures when compared with the controls. These were
      reductions in delusional conviction, general symptomatology and depression
      scores. Future studies should offer therapy over a longer period, targeting
      social as well as symptom change, and considering factors which will enhance
      maintenance of improvement.

PMID- 7803319
TI  - Personal constructs of survivors of childhood sexual abuse receiving cognitive
      analytic therapy.
AB  - Increasing numbers of survivors of childhood sexual abuse (CSA) are now seeking
      psychological therapy; yet little evidence currently exists concerning optimum
      treatment formats, especially when re-victimization has occurred in adulthood.
      This study reports an exploratory investigation of re-victimization, and of the
      use of cognitive analytic therapy (CAT) with seven CSA survivor women, six of
      whom had experienced re-victimization and five of whom were self-abusive. Results
      of single element and dyad grids administered before and after therapy were
      consistent with the exploratory hypothesis that abuse forms a central component
      of the women's relationships, hence making recurrence of abuse a real
      possibility. Outcome of therapy using CAT was positive, although the considerable
      and significant symptomatic changes observed were accompanied by significant
      change in only a relatively small number of the women's constructs, suggesting
      the persistence of the centrality of abuse despite therapy. For two women, levels
      of disturbance remained high after termination, and some evidence of relapse was
      also evident at three-month follow-up.

PMID- 7803320
TI  - The meaning of parenthood and couples' reactions to male infertility.
AB  - This paper reports findings from a postal survey of 205 couples belonging to the
      National Association for the Childless who saw their infertility as due to the
      male partner. Two self-report scales used in previous studies were administered
      to measure personal and social identity needs as a basis for parenthood (the
      Meaning of Parenthood scale), and emotional distress and marital problems.
      Endorsement of items on the Meaning of Parenthood (MOP) scale showed only small
      mean gender differences for each item and a consistent item rank order for men
      and women. Factor analysis confirmed that the scale tapped dimensions pertaining
      to social and personal identity needs. For women, distress was associated with
      ratings on the MOP scale which emphasized the link between femininity and
      motherhood, while for men distress was associated with ratings which emphasized
      masculinity and fatherhood. Implications of the results for further research and
      counselling in relation to male infertility are discussed.

PMID- 7803321
TI  - Recognition of the difficult airway in normal Nigerian adults (a prospective
      study).
AB  - Difficulty with laryngoscopy and intubation is known to be the most frequent
      cause of anaesthetic related deaths. Awareness of the possibility of difficulty
      would enable the anaesthetist to be adequately prepared. 57 "normal" adult
      patients were examined pre-operatively and at laryngoscopy using the Mallampatti
      (1985) and the Cormack (1984) classification respectively. The result showed that
      none of the patients was in the IV Mallampatti nor IV Cormack groups. Four
      patients with class III Mallampatti features were seen, two of which were
      classified Cormack III at laryngoscopy. Intubation failed in these two patients.
      The majority of patients were classified as Mallampatti class I (68.42%) and
      Cormack grade I (63.16%). This in effect demonstrates that in most "normal"
      patients laryngoscopy and intubation should be fairly easy.

PMID- 7803322
TI  - Experience with an in-patient treatment model for alcohol and drug dependence in
      Nigeria.
AB  - A new programme for the treatment of alcohol and drug dependence at the
      Neuropsychiatric Hospital, Aro, Abeokuta, Nigeria is based on the modified
      Minnesota/Therapeutic Community model. It therefore incorporates the disease
      concept of drug dependence and the 12-steps of Alcoholic Anonymous (AA). Chores
      and responsibilities are shared by all while learning experiences/sanctions are
      meted out for rule contravention. Most of the patients seen were forcibly brought
      by relatives, they were all males and polydrug abusers with no appreciable
      withdrawal symptoms during detoxification phase of the programme. About a third
      completed the treatment schedule. A sharp drop in abscondence rate was observed
      with the introduction of spiritual therapy. Experience showed that the patients
      had difficulty in conforming to rigid rules and staff had problems in coping with
      some of the complex issues of drug management.

PMID- 7803323
TI  - Symptomatology of temporal lobe epilepsy in Accra.
AB  - The symptoms of 80 patients diagnosed clinically and electro-encephalographically
      as suffering from temporal lobe epilepsy in Accra were studied. The symptoms
      included tonic and tonic-clonic seizures, vertigo, hallucinations, loss of
      consciousness and various behavioural abnormalities. The symptoms of T. L. E. in
      Accra are no different from elsewhere. The role of superstition in the African
      psyche in relation to epilepsy is stressed. The relationship between abnormal
      behaviour, epilepsy and psychosis is discussed. Delayed or inaccurate pathology
      are also discussed.

PMID- 7803324
TI  - The microflora of bile in Ghanaians.
AB  - Bile was obtained from the gall bladder of 104 patients undergoing
      cholecystectomy for gall stone disease. Bile was also obtained from the common
      bile duct and T-tube of 17 patients who also had exploration of common bile duct.
      During the same period, 148 cholecystectomies were performed. The specimens were
      sent for culture and sensitivity and 32.7% of the specimens grew bacteria. The
      factors that were associated with positive culture were emergency cholecystectomy
      for acute cholecystitis and empyema of gall bladder, carcinoma of gall bladder
      and obstructive jaundice. The commonest organisms were E. Coli (28.2%) and
      Klebsiella (17.9%). Pseudomonas surprisingly formed 10.2% of the cultured
      organisms. Salmonella that causes typhoid, which is an endemic disease in Ghana,
      formed only 7.7% of the isolates. Most of the organisms were resistant to
      Ampicillin and tetracyclines. The antibiotics that most were sensitive to were
      Gentamicin and Cefuroxime. Therefore the antibiotics that are recommended for use
      as prophylaxis in biliary tract surgery are Gentamicin or Cefuroxime.

PMID- 7803325
TI  - Oral slow-release nifedipine in the rapid treatment of severe hypertension in
      Nigerians.
AB  - The effect of the oral slow-release formulation of Nifedipine in rapidly lowering
      blood pressure was studied in 20 severely hypertensive Nigerians (8 males, 12
      females). A significant fall (p < 0.05) in mean systolic, diatolic, and mean
      arterial pressure was obtained 30 minutes after administration of Nifedipine. The
      fall in all three parameters of blood pressure remained sustained and significant
      (p < 0.05) 6 hours after a single dose administration. Side effects were minimal
      and limited to headaches in 20% of patients and palpitations in 10%. All patients
      showed a sustained control of blood pressure over a three month follow up period
      on slow release Nifedipine. Addition of methyldopa resulted in improved blood
      pressure control in one patient with chronic renal failure. It was concluded that
      oral slow release Nifedipine is a drug of choice in the rapid and sustained
      control of blood pressure in severely hypertensive patients especially in a
      setting where critical intensive monitoring facilities are limited.

PMID- 7803326
TI  - Clinical determination of maturity of newborn infants: comparison of some
      simplified methods.
AB  - A total of 508 infants were examined at three hospitals in Nigeria to evaluate
      the relative accuracy of maturity determination using 6 abbreviated and
      simplified methods in an African population. For each infant, total maturity
      scores were computed for each of the 6 methods and correlated with gestational
      age by simple regression analysis to construct regression lines of gestational
      age on total maturity score. The regression line for the 6 methods were used to
      determine the maturity of a prospective cohort of 262 infants and to evaluate
      accuracy of maturity determination with the Dubowitz methods as gold standard.
      Three simplified methods had comparable accuracy with the Dubowitz scoring
      system. This probably implies that simplified methods, developed from local
      populations, may not be universally applicable and reliable. Indeed, the method
      with the highest accuracy in this study was developed originally from an African
      population.

PMID- 7803327
TI  - The cost of sustaining the Ghana's "Cash and Carry" system of health care
      financing at a rural health centre.
AB  - This paper investigates the sudden fall in clinic attendance at a rural health
      centre. The pressure to sustain the cash and carry system of procuring drugs is
      being blamed for over prescription, inconsistent pricing of prescriptions and
      subsequent fall in clinic attendance. The clinic attendance which was dropping
      since the introduction of fee-for-service (1985) has now dropped sharply to about
      25% after the implementation of the Cash and Carry system (1990). Yet, the
      average revenue generated per patient has jumped from 201 cedis in 1990 to 348
      cedis in 1992. Analysis of the prescription pattern for malaria infection showed
      that 56% and 89% of patients received injections or were given three or more
      drugs in the free health service period and in the fee-for-service period
      respectively. Prescriptions which contained injections or more than three items
      yielded between 120% and 200% profit to the Health Centre compared to a profit of
      60% if only chloroquine and analgesics were prescribed. Consumptions of drugs by
      staff and non paying patients amounted to about 10% of the revenue generated from
      the paying patients. It is suggested that, at the health centre level, mechanism
      for pricing of prescriptions to patients must be reviewed, since motivation for
      profit could influence the management of diseases and also the use of health
      facilities. Secondly, refund for drugs consumed by staff and non-paying patients
      must be recovered in order to remove undue pressure to make profit.

PMID- 7803328
TI  - Computerized tomographic findings in adolescent and adult Nigerian epileptics.
AB  - We evaluated CT findings in 75 Nigerians who suffer from epilepsy aged 12 years
      and over to determine factors associated with positive yield for judicious
      utilisation of CT. There were 48 males and 27 females with a mean age of 36 +/-
      15 years. CT was normal in 41 subjects (54.7%). The commonest CT abnormality was
      cortical atrophy encountered in 16 subjects. The other abnormalities were
      occupying lesions (13) comprising 11 neoplasms and 2 subdural haematoma, vascular
      lesions (4) and poroencephaly (1). The presence of CT abnormality was
      statistically significantly associated with neurologic deficit, partial seizure
      type and EEG abnormalities (P < 0.05). The decision on when to request CT scan in
      epileptics could therefore be influenced by our findings.

PMID- 7803329
TI  - Pregnancy following infertility due to pelvic schistosomiasis--a case report.
AB  - A case of infertility due to bilateral tubal blockage secondary to pelvic
      schistosomiasis in a Nigerian woman is presented. Intra uterine pregnancy
      followed treatment by peritubal adhesiolysis and the use of niridazole.

PMID- 7803331
TI  - Midazolam in emergency surgery--a pilot study on adult Nigerian patients.
AB  - The effectiveness and safety of midazolam in induction of anaesthesia was studied
      in 15 ASA class II or III patients who required emergency surgery. In each case a
      slower and smoother transition at induction of anaesthesia was desired, as well
      as cardiovascular stability. All patients received 0.5 mg atropine and midazolam
      premedication (10-12.5 mg i.m) 20 to 30 minutes before induction. Anaesthesia was
      induced with 0.2 mg/kg of midazolam administered intravenously over 30 seconds.
      The induction time, degree of anterograde amnesia and incidence of local
      tolerance were evaluated. The pulse rate, blood pressure and ECG were monitored
      and recorded throughout the duration of surgery. The recovery time was also
      assessed. The mean induction time was 82.73 seconds and transition was smooth in
      all cases. Tolerability was good as well as the amnestic effect. Outcome was
      rated as very good in terms of cardiovascular stability and all the patients
      recovered rapidly.

PMID- 7803330
TI  - Midazolam in gynaecology: the Nigerian experience.
AB  - In a pilot survey, 11 female patients of ASA grade I, undergoing short elective
      surgery, received midazolam 0.5 to 0.2 mg/kg for induction of anaesthesia.
      Indication for surgery was therapeutic or diagnostic evacuations. No narcotic
      premedication was given, however atropine 0.5 mg i.v. was given at induction just
      before pre-oxygenation. Anaesthesia was maintained with N20/O2 and halothane 1-3%
      and ventilation was spontaneous. The study showed that although midazolam did not
      produce narcosis as rapidly as thiopentone it was devoid of any marked
      respiratory or cardiovascular depressant effect. Narcosis was however induced
      within 81 seconds of injection. Midazolam also exhibited an additional anxiolytic
      effect. No local or system adverse reaction were observed on the day of surgery.
      There was no incidence of apnoea and no case of post operative vomiting. There
      was marked anterograde amnesia, only 20% of the patients had some recall of
      events preceeding induction (just about 30% of events could be remembered). It
      was therefore concluded that in view of the foregoing, combined with the fact
      that midazolam injection was painless, recovery rapid and amnesic properties
      good, midazolam is a drug of choice for day stay surgery.

PMID- 7803332
TI  - Open comparative study of the efficacy, safety and tolerability of midazolam
      versus thiopental in induction and maintenance of anaesthesia.
AB  - In a multicentre study, 145 adult Nigerian patients presenting with diverse
      conditions (falling into ASA1 or ASA2 classification) for short surgical
      procedures (< 1 hour) were given either midazolam (0.15-0.20 mg/kg) or
      thiopentone (4-6 mg/kg) intravenously for induction of anaesthesia. Study
      population consisted of 58 male and 89 female patients with a mean age of 33.5 +/
      10.42 years. The primary efficacy criteria for induction of anaesthesia was
      induction time measured by the time of spontaneous closing of eyes and
      disappearance of palpebral reflexes following injection of trial drug. For
      maintenance of anaesthesia efficacy was assessed by the requirement of an
      additional dose of the anaesthetic agent either alone or in combination with
      other agents in addition to N20/O2 mixture. The secondary efficacy criteria was
      the degree of anterograde amnesia produced by trial drug, this was assessed by
      memory test. Safety was assessed by the frequency of the incidence of apnoea and
      cardio-stability measured by changes in the haemodynamic parameters (BP and
      pulse). Tolerability was evaluated by incidence of phlebitis or pain at the
      injection site. The standard efficacy population was all the 145 patients while
      only 100 patients were considered evaluable for maintenance efficacy. The mean
      induction time was 67.28 +/- 63.36 secs and 31.28 +/- 13.01 secs for the
      midazolam and thiopentone groups respectively. Anaesthesia was maintained with
      N20/O2 alone in 47% of patients in the midazolam group compared with 28.6% of
      patients in the thiopentone group. The degree of anterograde amnesia was
      significantly more pronounced in the midazolam group than in the thiopentone
      group (p = 0.000).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7803333
TI  - Significance of antibiotics resistance amongst clinical bacterial isolates in
      Lagos.
AB  - In vitro susceptibility of several strains of six different species of clinical
      facultative pathogens involved in nosocomial infections in our hospital was
      investigated by a series of disc diffusion, broth dilution and Chequerboard
      titration testing. With disc diffusion method all the test strains, except
      Streptococcus pyogenes, were resistant to penicillin. 46% of the Klebsiella
      aerogenes and 73% of the Pseudomonas strains were generally resistant to
      cefotaxime. The minimum inhibitory concentration (MIC) of the antibiotics
      correlated well with the results of the disc diffusion tests. Synergistic effects
      were demonstrated by various combinations of gentamicin, ampicillin, clindamycin,
      colistin, cefoxitin, and ceftriazone against resistant strains of S. aureus,
      Pseudomonas aeruginosa, Escherichia coli and Klebsiella aerogenes. Against S.
      aureus the effect of gentamicin/clindamycin demonstrated indifference. The need
      for stringent caution is strongly advocated in the selection of combination
      therapy for serious infections caused by some hospital bacterial strains
      particularly in acute care units. The clinical microbiologist should be consulted
      at all times during the process of selection of an appropriate combined therapy
      for expert guidance.

PMID- 7803334
TI  - Intususception in infancy and childhood: an analysis of 69 cases.
AB  - A retrospective study of 69 cases of intususception treated at the University of
      Port Harcourt Teaching Hospital, Port Harcourt in the past seven years from
      October, 1985 to September, 1992 is presented. The diagnosis was made clinically
      and confirmed at operation. Fifty (72.5%) of the 69 patients belonged to the
      three to nine month age group. There was a male preponderance; male to female
      ratio 3.6:1. The classic triad of abdominal pain, rectal bleeding and abdominal
      mass occurred in only 11 patients (15.9%). All 69 patients had laparotomy as
      reduction using barium enema was not attempted. Of the 35 patients who required
      resection 27 (77.1%) had gangrenous bowel and 2 (2.8%) had perforation as well.
      Mortality was 11.6%. The high mortality rate appears to be related to the long
      interval between onset of symptoms and commencement of definitive treatment.

PMID- 7803335
TI  - Pattern of substance use amongst secondary school students in Ilorin, northern
      Nigeria.
AB  - One thousand and forty one Senior secondary School Students in Ilorin, Kwara
      State, Nigeria were surveyed using a 117-items self-administered substance use
      questionnaire in May 1988. Males constituted 56.6% and Females 43.5% of the study
      population. The mean age was 16.8 years (S.D. 1.84). The most currently used
      substances were found to include salicylate analgesics (56.2%), antibiotics
      (23.6%), stimulants (21.6%), alcohol (12.0%) and cigarette (4.4%). Current use of
      alcohol, antibiotics and salicylate analgesic was significantly more common in
      the rural school. Current use of cigarette and cannabis occurred significantly
      more in the male population while no significant sex differences were noted for
      the other drugs surveyed. For many students, initiation into substance use
      started at primary school level. The need to monitor the pattern of substance use
      at all levels of our educational system (primary, secondary and post-secondary)
      and to develop adequate preventive programmes for the student population was
      emphasized.

PMID- 7803337
TI  - Extra-oral prosthetics: past and present.
AB  - The field of maxillofacial prosthetics is concerned with the prosthetic
      reconstruction of missing head and neck tissue. A prosthetic replacement of an
      exterior part is termed an epithesis. Beautiful examples of such prostheses were
      described as early as the 17th century. Often these defects were caused by war
      traumas or accidents. Currently, facial prostheses are usually applied in cases
      of defects caused by the surgical removal of tumors or congenital defects.
      Retention of devices has always been problematic. The contributions that implants
      can make to solve these problems are discussed by examining some cases.

PMID- 7803336
TI  - The African AIDS case definition and HIV serology in medical in-patients at Komfo
      Anokye Teaching Hospital, Kumasi, Ghana.
AB  - In 914 consecutive medical admissions to Komfo Anokye Teaching Hospital, the
      prevalence of infection with Human Immunodeficiency Virus type I (HIV-I) and
      Human Immunodeficiency Virus type 2 (HIV-2) was 12.6%. The prevalence in females
      was twice that found in males. The infection rate was maximum in the age group 25
      29 years for females (45%) and 30-34 years for males (29%). There were 7 cases
      infected with HIV-2 alone, 55 cases infected with HIV-I alone and 53 cases with
      dual infection. The cases with HIV-2 infection tended to be older than those with
      HIV-I infection. For detecting HIV seropositivity in our patients the World
      Health Organization recommended case definition for AIDS in Africa gave a
      sensitivity of 32%, a specificity of 93% and a positive predictive value of 42%.
      The case definition gave the highest specificity and positive predictive values
      when cases of tuberculosis were not included in the analysis.

PMID- 7803338
TI  - Indications for extra-oral implantology.
AB  - In this paper, the general indications for implantology for facial prosthesis in
      the maxillofacial bones are elaborated. Information from both the literature and
      our own surgical experience emphasizes that only specific locations of the facial
      bones and skull are suitable for implant fixtures. Careful indication and surgery
      are required for patients who were exposed to radiotherapy. The success of
      maxillofacial rehabilitation depends on multidisciplinary cooperation.

PMID- 7803339
TI  - Fixation of auricular prostheses by osseointegrated implants.
AB  - Placement of enosseous implants in the temporal bone may overcome the apparent
      disadvantages of skin adhesives and skinpockets for the fixation of auricular
      prostheses. The surgical procedure for placement of implants in the temporal bone
      and the results obtained in eight patients wearing implant-supported auricular
      prostheses are described. From the results of this study, it is obvious that
      osseointegrated implants have great advantages compared with skin adhesives and
      skinpockets to rehabilitate patients suffering from auricular defects. The major
      achievement of implant-supported auricular prostheses is the patients' increased
      comfort and confidence wearing these types of prostheses.

PMID- 7803340
TI  - Use of implants for prosthetic rehabilitation after cancer treatment: clinical
      experiences.
AB  - Treatment of patients with head and neck cancer may result in extensive intra- or
      extra-oral defects. Prosthetic rehabilitation often will be limited by
      insufficient retention and an atrophic mucosa or skin. In such cases,
      osseointegrated implants may offer substantially improved retention for the often
      complex prosthetic constructions. However, irradiation has a negative influence
      on the bone growth capacity and thus on osseointegration. Based on experimental
      studies, a recovery period of 6 to 12 months after irradiation is recommended.
      Because of the risk of failure and the lack of sufficient and sound scientific
      knowledge, clinical studies of titanium implants inserted in previously
      irradiated bone tissue have had varying results. This paper discusses the typical
      requirements of implant suprastructures for resection prostheses. Some of the
      patient histories and clinical management presented illustrate the possibilities
      of implants in the field of maxillofacial reconstruction.

PMID- 7803341
TI  - Procedure for fabrication of an implant-supported auricular prosthesis.
AB  - The procedure for fabrication of an implant-supported auricular prosthesis is
      described. Treatment is started during the preparatory phase of the surgical
      procedure because a favorable position of the implants for the epithesis must be
      chosen at that stage. The fabrication of an epithesis requires close
      collaboration among the prosthodontist, the maxillofacial technician, and the
      patient. First, a suprastructure is fabricated on the implants. It consists
      mostly of rings and a bar connecting the implants. The base of the epithesis
      consists of hard acrylic resin, which contains clips that provide the retention
      for the epithesis. The epithesis itself consists of silicone rubber. Great care
      must be taken in shaping and coloring the epithesis.

PMID- 7803342
TI  - Facial disfigurement after cancer resection: a problem with an extra dimension.
AB  - Treatment of patients with maxillofacial defects includes not only the technical
      procedures involved in producing a prosthesis, but also the psychosocial aspects.
      In all cases, these patients must learn to live with a severe facial
      disfigurement. People born with congenital defects grow up with disfigurement.
      For cancer patients, in addition to the mutilation, fear of the tumor plays a
      significant role. This paper reports on research into this specific treatment
      aspect. Such patients first must learn to cope with the possibility of premature
      death. They then must learn to accept facial disfigurement and the fact that
      society will respond differently to them.

PMID- 7803343
TI  - Percutaneous titanium implantation in the skull for the bone-anchored hearing
      aid.
AB  - In the 1980s, a new type of bone conduction hearing aid was developed in
      Goteborg, Sweden. With this new bone-anchored hearing aid (BAHA) system, sound
      waves are transmitted directly to the skull by means of a titanium screw
      implanted into the skull. The advantages and disadvantages of the conventional
      hearing aid and the BAHA are described here. In the 25 patients presented, all
      the percutaneous implants remained firmly anchored in the skull. One screw was
      lost through trauma. The scores on the speech recognition-in-noise and the speech
      recognition-in-quiet tests were significantly higher in 64% and 32% of the
      patients with a BAHA, respectively.

PMID- 7803344
TI  - The future of extra-oral implantology.
AB  - In this paper conclusions are drawn from the experiences of subjects presented in
      the previous studies in this issue. Indications for bone-anchored implants, the
      percutaneous passage, implant placement in irradiated tissues, and the
      psychosocial aspects of treatment are discussed in detail. The future of the
      extra-oral implantology is also discussed. There is some experience with using
      bone-anchored implants extra-orally, but both medical and dental staff and the
      patients themselves are reluctant to use them. In the future, this might change
      when the percutaneous passage is improved, when hyperbaric oxygen therapy is
      generally used, when there is more insight into all the possibilities and
      limitations of bone-anchored devices, and when their application is generally
      accepted.

PMID- 7803345
TI  - Registration of blind and partially sighted people.

PMID- 7803346
TI  - Combined trabeculotomy-trabeculectomy for congenital glaucoma.

PMID- 7803347
TI  - Unrecognised and unregistered visual impairment.
AB  - Recent community based studies have shown that only a minority of visually
      impaired people who are eligible to be registered as partially sighted or blind
      are actually registered as such. To determine how many unregistered but eligible
      people are attending ophthalmic clinics a prospective study was undertaken of all
      patients (n = 1543) attending ophthalmic outpatient departments, at a single
      specialty eye hospital and two district general hospitals over a 1 week period.
      All patients with visual acuity < or = 6/18 or restricted visual field were
      interviewed. Registration status and factors affecting this were then determined.
      Although 95/174 patients interviewed were eligible for registration, 68 as
      partially sighted and 27 as blind, only 46 (48.4%) of these were registered.
      Asians and Afro-Caribbeans were under-represented in the group eligible for
      registration. Active treatment impeded registration. Patients having four or more
      hospital visits were on average 16 times more likely to be registered as those
      who had fewer attendances. Disabilities, in addition to visual impairment, were
      present in 40% (n = 38). This study shows that there is unregistered visual
      impairment in patients attending ophthalmic departments. As registration triggers
      multidisciplinary support, ophthalmologists need to be more alert to the benefits
      and criteria for partial sight and blind registration.

PMID- 7803348
TI  - Loss of vision before ophthalmic referral in blind and partially sighted
      diabetics in Bristol.
AB  - Data from all patients registered blind from diabetic retinopathy in Avon during
      a 16 month period were analysed with regard to management before hospital
      referral. The main findings were: 50% of the patients had no screening for
      retinopathy and were known to be diabetic; 25% were regularly screened for
      retinopathy (three quarters by local opticians); 22% were newly diagnosed as
      diabetic at the time of hospital referral. The degree of visual loss at the time
      of first hospital attendance was found to be marked (average 4.4 Snellen lines of
      acuity) but was not significantly different for different sources of referral.
      Only one eye of one patient had normal acuity at first attendance and 88% had
      lost two or more lines; 72% of registrations were a result of diabetic
      maculopathy. Delay from waiting for hospital appointments did not contribute
      significantly to the outcome in the group of patients studied.

PMID- 7803349
TI  - Combined trabeculotomy-trabeculectomy compared with primary trabeculectomy for
      congenital glaucoma.
AB  - This paper aimed to assess the outcome of primary trabeculectomy for congenital
      glaucoma and to compare it with a combined trabeculotomy-trabeculectomy
      procedure. The combined procedure was assessed using a prospective trial for
      children with primary glaucoma under the age of 1 year (n = 16). The primary
      trabeculectomy was assessed retrospectively using similar patients treated at the
      same hospital from 1981 to 1990 (n = 44). After 24 months of follow up, the
      cumulative chance of success of the primary trabeculectomy was 72% and this was
      compared with the combined procedure of 93.5%. Primary trabeculectomy achieved
      good intraocular pressure control for up to 10 years. Follow up for the combined
      procedure ranged from 19 to 27 months. Complications included hyphaema (4/16 and
      4/44) and cataract (0/16 and 3/44). Primary trabeculectomy for congenital
      glaucoma gives adequate long term success with few complications. The combined
      procedure may have a higher success rate and this requires further investigation.

PMID- 7803350
TI  - Effect of diabetes associated increases in lens optical density on colour
      discrimination in insulin dependent diabetes.
AB  - Optical density (OD) of the crystalline lens has been shown in non-diabetics to
      increase linearly with age over the first five decades and at an increased rate
      thereafter; in insulin dependent diabetic (IDDM) patients, lens OD increases with
      age and with duration of diabetes at a rate similar to that in non-diabetics over
      the age of 60 years. Recently, it has been established that colour discrimination
      is abnormal in a majority of young patients with uncomplicated IDDM and
      angiographically normal retinas. Colour discrimination loss was attributed to
      functional abnormalities in the retina or neural pathways; yet the possibility
      exists that increases in lens OD may account for part or all of the colour
      discrimination loss in IDDM. In the present study, colour discrimination was
      compared in aretinopathic IDDM patients and age-matched controls, and then in a
      group of aretinopathic IDDM patients individually matched to controls with
      respect to lens OD. Colour discrimination was significantly worse in diabetic
      patients than in age-matched controls, and was significantly worse when diabetic
      patients were compared with controls matched for OD. The magnitude of the
      difference in 100 hue error score between diabetic patients and OD matched
      controls was, however, considerably less than the difference between diabetic
      patients and age-matched controls. These data suggest that colour discrimination
      loss in aretinopathic IDDM patients cannot be explained solely on the basis of
      diabetes induced increases in lens OD, but must involve abnormalities of the
      retina or its neural connections.

PMID- 7803351
TI  - Retinal findings in Malawian patients with AIDS.
AB  - The purpose of this study was to determine the prevalence of retinal disease in a
      group of patients with AIDS in Malawi. Indirect ophthalmoscopy was performed on
      99 patients with AIDS who were admitted consecutively to a medical ward at a
      central hospital. Necrotising retinitis was present in one eye of one patient
      examined. Non-infectious retinopathy was present in 13%. Retinitis is less common
      in AIDS patients from Africa compared with those from developed countries; it is
      believed that most patients die before acquiring it. Non-infectious retinopathy
      may also be less common.

PMID- 7803352
TI  - Optic nerve head analyser and Heidelberg retina tomograph: accuracy and
      reproducibility of topographic measurements in a model eye and in volunteers.
AB  - The accuracy and reproducibility of the optic nerve head analyser (ONHA) and the
      Heidelberg retina tomograph (HRT) were compared and the performance of the HRT in
      measuring fundus elevations was evaluated. The coefficient of variation of three
      repeated measurements in a model eye and in volunteers and the relative error in
      a model eye was calculated. With ONHA measurements the pooled coefficient of
      variation in volunteers was 9.3% in measuring cup areas and 8.4% in measuring the
      cup volume. In a model eye the pooled coefficient of variation was 7.6% for the
      parameter 'cup area' and 9.9% for the parameter 'cup volume'. The pooled relative
      error in the model eye was 6.6% for the parameter 'cup area' and 5.1% for the
      parameter 'cup volume'. With HRT measurements in volunteers the pooled
      coefficient of variation of both the parameters 'volume below contour' and
      'volume below surface' was 6.9%. In the model eye the pooled coefficient of
      variation was 2.4% for the 'volume below contour' and 4.1% for the parameter
      'volume below surface'. The pooled relative error in the model eye was 11.3% for
      the 'volume below contour' and 11% for the 'volume below surface'. The pooled
      relative error in measuring retinal elevations in the model eye was 3.8%. The
      coefficient of variation was 3.5%. The accuracies of the HRT and ONHA were
      similar. However, as the ONHA 'cup volume' is unreliable in patients because of
      the design of the ONHA whereas the HRT volume parameters are reliable it seems
      reasonable to assume that the HRT is superior to the ONHA. Only the HRT is
      capable of quantifying retinal elevations.

PMID- 7803353
TI  - Cryotherapy for trichiasis in ocular cicatricial pemphigoid.
AB  - Trichiasis is a common and potentially sight threatening complication of ocular
      cicatricial pemphigoid and is usually secondary to cicatricial entropion. This
      study aimed to assess the success and complications of eyelid cryotherapy for
      trichiasis in a group of patients with long term follow up. The case records of
      all patients with ocular cicatricial pemphigoid that attended the external
      disease clinic at Moorfields Eye Hospital from 1980 to 1992 were reviewed. Each
      eyelid was divided into three horizontal zones. Cryotherapy was delivered with an
      Amoilette cryoprobe for approximately 30 seconds. Failure of the cryotherapy was
      defined as a regrowth of the eyelashes within the treated zone that either
      required epilation for symptom control or caused keratopathy. Ninety two lid
      zones were treated, involving 25 lids of 12 patients. The cumulative chance of
      success decreased rapidly to 40% over the first year. Thereafter, the chance of
      success declined slowly to 34% at 4 years. Complications included lid notching (n
      = 2), tarsal atrophy (n = 1), altered lid contour (n = 1), and temporarily raised
      intraocular pressure (n = 1). All patients had quiescent disease at the time of
      the cryotherapy and no patients showed increased conjunctival disease activity
      after treatment. Six patients were taking systemic immunosuppression medication.
      When ocular cicatricial pemphigoid is quiescent, lid cryotherapy has an
      acceptable complication rate. The major reason for recurrence of the trichiasis
      was attributed to inadequate follicle freezing.

PMID- 7803354
TI  - Lack of effect of preoperative norfloxacin on bacterial contamination of anterior
      chamber aspirates after cataract surgery.
AB  - Eighty patients undergoing routine standardised extracapsular cataract surgery
      with lens implantation were divided randomly into two groups in a prospective
      double blind study comparing effects of preoperative norfloxacin eyedrops with
      placebo on bacterial contamination of anterior chamber aspirates after surgery.
      Pathogenic organisms were identified from 19 (24%) of the aspirates. The most
      commonly isolated organisms were coagulase negative Staphylococcus species. There
      was no statistical difference between the norfloxacin treated and placebo groups.
      This study demonstrates that routine use of topical preoperative antibiotics to
      eliminate the entry of bacteria into the eye during surgery is debatable.

PMID- 7803355
TI  - Optic disc measurement with the Zeiss four mirror contact lens.
AB  - A knowledge of the optic disc size may be of value when assessing the glaucoma
      suspect. The vertical diameter of the optic disc was measured using a Zeiss four
      mirror gonioscope and a 900 Haag-Streit slit-lamp in one eye of 39 patients, 32
      with refractive errors within 3 dioptres of emmetropia. The disc was measured by
      projecting a slit beam of known height onto the image of the disc. A
      magnification factor for the contact lens was calculated from first principles
      and disc height recalculated. These measurements were compared with those
      obtained by photographic methods using the corrections suggested by Bengtsson and
      Krakau. In the analysis on the 32 eyes within 3 dioptres of emmetropia the best
      correlation with clinical measurements was obtained with correction 3 using
      spectacle refraction and keratometry (r = 0.8614). The contact lens measurement
      was within plus or minus 0.1 mm of the photographic measurement in 67% of cases
      and plus or minus 0.2 mm in all cases. This simple method is advocated for the
      routine assessment of optic disc size.

PMID- 7803356
TI  - Biometry in X linked megalocornea: pathognomonic findings.
AB  - Biometric study in a series of 11 affected males provides characteristic
      findings. The patients present with a large cornea with short radius, very deep
      anterior chamber depth (AC depth) exceeding the normal mean value of plus 2 SD,
      and a short vitreous length. Calculation of the postlimbal depth, a method
      applied in this study to obtain information about positioning of the iris and the
      lens, reveals a posterior positioning of the iris and lens. The posterior
      positioning of the iris and lens was proved to occur at the expense of the
      vitreous. The importance of biometric data for diagnosis and for differential
      diagnosis in primary infantile glaucoma and other diseases with megalocornea is
      discussed.

PMID- 7803357
TI  - Comparison of the expression of interferon gamma, IL2, IL4, and lymphotoxin mRNA
      in experimental autoimmune uveoretinitis.
AB  - The aim of this study was to investigate the T lymphocyte subsets involved in
      experimental autoimmune uveoretinitis (EAU) by quantifying the numbers of cells
      expressing mRNA for each of the lymphokines interferon gamma, interleukin 2,
      interleukin 4, and lymphotoxin throughout the disease process. Lewis rats were
      immunised with retinal S-antigen to provide a model of inflammatory eye disease.
      In situ hybridisation using cDNA probes specific for interferon gamma, IL2, IL4,
      and lymphotoxin mRNA were utilised to localise lymphokine mRNA expression by
      infiltrating cells and the numbers of positive cells counted. Localisation of
      mRNA for all four probes was found on increasing cell numbers as the disease
      process progressed. Similar numbers of cells expressed mRNA for each lymphokine,
      generally a small percentage of the T lymphocyte total. Activated cells within
      the eye express mRNA for interferon gamma, IL2, IL4, and lymphotoxin in EAU
      suggesting a mixed population of T lymphocyte subsets.

PMID- 7803359
TI  - Eyesight and the public services.

PMID- 7803358
TI  - Low glutathione reductase and peroxidase activity in age-related macular
      degeneration.
AB  - Age-related macular degeneration (ARMD) may result from events initiated by
      reactive oxygen species. Blood samples from 18 patients with ARMD and 18
      similarly aged controls were analysed for activities of important antioxidants.
      Blood glutathione reductase activity was lower in patients with ARMD compared
      with controls (p = 0.035). The activities of glutathione peroxidase (p = 0.18)
      and erythrocyte superoxide dismutase (p = 0.29) were similar between the two
      groups by a Student's two sample t test. Logistic regression was used to
      determine which enzyme activities were associated with ARMD after adjusting for
      possible confounding variables: smoking history, age, multivitamin use, and
      cardiovascular disease. Glutathione reductase activity (p = 0.05) and glutathione
      peroxidase activity (p = 0.065) were significantly associated with ARMD by this
      analysis. The relation of glutathione reductase and glutathione peroxidase
      activity to ARMD merits further study.

PMID- 7803361
TI  - Understanding of the retinal circulation provided by an anomalous retinal vein.

PMID- 7803360
TI  - Contrast sensitivity testing in clinical practice.

PMID- 7803362
TI  - Mechanism related to the lateral rectus muscle capable of retracting the outer
      canthus of the eye.

PMID- 7803364
TI  - Superglue accidents and the eye--causes and prevention.

PMID- 7803363
TI  - Multiple vortex vein varices masquerading as choroidal secondaries.

PMID- 7803365
TI  - Excimer laser PRK and corticosteroid induced IOP elevation: the tip of an
      emerging iceberg?

PMID- 7803366
TI  - Phenelzine reduces plasma vitamin B6.
AB  - Plasma levels of the active form of vitamin B6 (pyridoxal phosphate) in 19
      patients taking phenelzine were found to be reduced on the average to
      approximately 54% of the value in a control group. There was no correlation of
      pyridoxal phosphate level with phenelzine daily dosage over the range of 30 mg to
      90 mg. No symptoms of vitamin B6 deficiency peripheral neuropathy were found.

PMID- 7803367
TI  - REM sleep abnormalities and psychiatry.
AB  - Since the 1950s, with the discovery of REM sleep and its relationship to
      dreaming, psychiatric sleep researchers have been interested in uncovering the
      complex relationship between disturbed sleep and psychiatric disorders. This
      paper reviews the alterations in REM sleep of relevance to psychiatry and
      indicates that continued developments in sleep research may assist in further
      understanding the neuropathophysiology of affective and other psychiatric
      illnesses.

PMID- 7803369
TI  - Sleep oscillations and their blockage by activating systems.
AB  - There are three major oscillations in thalamocortical systems during the state of
      sleep with synchronization of the electroencephalogram: 1. Spindles (7 Hz to 14
      Hz) are generated in the thalamus at sleep onset and are blocked during arousal
      or rapid-eye-movement sleep by cholinergic systems that decouple the
      synchronizing network of the reticular thalamic nucleus. 2. Delta potentials (1
      Hz to 4 Hz) appear during late stages of electroencephalogram-synchronized sleep.
      At the thalamic level they are produced by the interplay between two intrinsic
      currents of neurons with cortical projections. Delta rhythm is suppressed by
      cholinergic and noradrenergic systems. 3. A slow oscillation (< 1 Hz) is
      generated in the cerebral cortex and has a pivotal role in grouping the thalamic
      generated sleep rhythms within wave-complexes recurring periodically, every two
      to five seconds. The slow rhythm is blocked by cholinergic and noradrenergic
      projections. Sleep rhythms consist of long-lasting inhibitory components that
      obliterate synaptic transmission and disconnect the brain from the outside world.

PMID- 7803368
TI  - Light, melatonin and the sleep-wake cycle.
AB  - Blood levels of the pineal hormone melatonin are high at night and low during the
      day. Its secretion is regulated by a rhythm-generating system located in the
      suprachiasmatic nucleus of the hypothalamus, which is in turn regulated by light.
      Melatonin is regulated not only by that circadian oscillator but acts as a
      darkness signal, providing feedback to the oscillator. Melatonin has both a
      soporific effect and an ability to entrain the sleep-wake rhythm. It also has a
      major role in regulating the body temperature rhythm. Melatonin rhythms are
      altered in a variety of circadian rhythm disorders. Melatonin treatment has been
      reported to be effective in treatment of disorders such as jet lag and delayed
      sleep phase syndrome.

PMID- 7803370
TI  - Central nervous system and peripheral immune functions and the sleep-wake system.
AB  - This paper reviews the relationship of aspects of the immune system to the sleep
      wake system in animals and humans. In addition to the influence of certain
      cytokines such as interleukin-1 (IL-1) on the sleeping-waking brain, circadian
      measures of plasma IL-1 and peripheral immune cellular functions, for example,
      natural killer cell activities and cortisol are related to the sleep-wake system
      in humans. Changes in the circadian patterns of immune functions over the
      menstrual cycle are associated with the amount of progesterone and slow wave
      sleep. The harmonious inter-relationship of the circadian pattern of the immune,
      endocrine and sleep-wake systems may be important in the cause and functions of
      sleep.

PMID- 7803371
TI  - Cognitive deterioration from long-term abuse of dextromethorphan: a case report.
AB  - Dextromethorphan (DM), the dextrorotatory isomer of 3-hydroxy-N-methylmorphinan,
      is the main ingredient in a number of widely available, over-the-counter
      antitussives. Initial studies (Bornstein 1968) showed that it possessed no
      respiratory suppressant effects and no addiction liability. Subsequently,
      however, several articles reporting abuse of this drug have appeared in the
      literature. The drug is known to cause a variety of acute toxic effects, ranging
      from nausea, restlessness, insomnia, ataxia, slurred speech and nystagmus to mood
      changes, perceptual alterations, inattention, disorientation and aggressive
      behavior (Rammer et al 1988; Katona and Watson 1986; Isbell and Fraser 1953;
      Devlin et al 1985; McCarthy 1971; Dodds and Revai 1967; Degkwitz 1964; Hildebrand
      et al 1989). There have also been two reported fatalities from DM overdoses
      (Fleming 1986). However, there are no reports describing the effects of chronic
      abuse. This report describes a case of cognitive deterioration resulting from
      prolonged use of DM.

PMID- 7803372
TI  - Obsessive-compulsive symptomatology in normal pressure hydrocephalus: a case
      report.
AB  - This report describes a patient with a DSM-III-R diagnosis of obsessive
      compulsive disorder and a nuclear magnetic resonance picture of a normal pressure
      hydrocephalus. After neurosurgery, the patient showed marked improvement in his
      compulsions which previously had shown little response to pharmacological
      treatment.

PMID- 7803373
TI  - Cognitive decline in schizophrenic patients: relationship to other symptoms.

PMID- 7803374
TI  - Tranylcypromine withdrawal: is it more common than we realize?

PMID- 7803375
TI  - Schizophrenia research. Psychosocial.

PMID- 7803376
TI  - Schizophrenia research. Service delivery.

PMID- 7803377
TI  - Schizophrenia research. Psychopharmacology.

PMID- 7803378
TI  - A national strategy for research on Schizophrenia. Introduction.
AB  - The National Strategy for Research on Schizophrenia currently consists of
      research priorities and a proposed structure for collaboration. Research panels
      have already come up with priorities in six different fields of research. The
      National Strategy will assist researchers in submitting proposals that fit in
      with the priorities. It will also encourage cooperation between researchers,
      clinical centres, consumers (patients) and families. This will help to prevent
      duplication of effort, and to focus research on the areas most likely to yield
      important results. The National Strategy will grow and change along with the
      nature of research in Canada and elsewhere. The credibility of the strategy rests
      on how well it reflects the interests and concerns of researchers, consumers and
      caregivers. The ultimate test will be its effectiveness in supporting and
      promoting research. This will occur when researchers acknowledge the strategy in
      their research proposal submissions, and funding agencies see this
      acknowledgement as a strength. The common core of the strategy is the
      administrative and coordinating structure of CAROS. CAROS plans to continue
      working with the research panels as they update their priorities, and these will
      be reviewed by interested stakeholders, especially consumers and families. CAROS
      also will maintain a database of ongoing research and will serve as a source of
      contact for researchers. Of special importance in implementing the National
      Strategy is the coordination of clinical centres. These clinical centres, many
      identified through the hospital system, may already be involved in research on
      schizophrenia and may be linked to existing research centres.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7803380
TI  - Schizophrenia research. Neurobiology/imaging.

PMID- 7803379
TI  - Schizophrenia research. Genetics.

PMID- 7803381
TI  - Report on Canadian research activity in schizophrenia. Canadian Alliance for
      Research on Schizophrenia (CAROS).

PMID- 7803382
TI  - Schizophrenia research. Methodology & instrumentation.

PMID- 7803383
TI  - Modulation of the GTPase activity of transducin. Kinetic studies of reconstituted
      systems.
AB  - We seek to define the influence of retinal cGMP phosphodiesterase (PDE) on the
      GTPase activity of transducin (T). A novel stopped-flow/fast filtration apparatus
      [Antonny, B., et al. (1993) Biochemistry 32, 8646-8653] is used to deliver T
      alpha GTP free of rod outer segment (ROS) membranes to a suspension of
      phospholipid vesicles bearing holoPDE. As measured by a pH electrode, the decay
      of cGMP hydrolysis from these samples, which contain no other proteins but T
      alpha and holoPDE, requires GTP hydrolysis and occurs in 40 s. The addition of T
      beta gamma to the vesicles does not accelerate this deactivation. When ROS
      membranes are urea-stripped, reconstituted with transducin + holoPDE, and
      illuminated, the injection of an amount of GTP that is substoichiometric to
      holoPDE gives a cGMP hydrolysis pulse that lasts for 30 s. However, the same
      reconstitution performed with ROS stripped by extensive dilution in isotonic
      buffer results in a deactivation time of only 8 s, which resembles the 7 s
      observed with native ROSs. With these isotonically stripped ROSs, when GTP
      injection comes after a first injection with GTP gamma S, the cGMP hydrolysis
      pulse is lengthened and lasts for 17 s; with urea-washed ROS, no such lengthening
      is observed. These results clearly demonstrate that holoPDE by itself cannot
      enhance the GTPase activity of transducin, even when the two proteins are
      localized on a membrane surface. Instead, they point to the existence of a
      membrane-bound, urea-sensitive protein factor that activates the GTPase of T
      alpha in the transducin-holoPDE complex.

PMID- 7803384
TI  - Biosynthesis of conjugated triene-containing fatty acids by a novel isomerase
      from the red marine alga Ptilota filicina.
AB  - The biosynthesis of conjugated triene-containing fatty acids by the red alga
      Ptilota filicina is catalyzed by a novel enzyme, polyenoic fatty acid isomerase.
      The enzyme has been highly purified and is described here for the first time.
      Matrix-assisted laser-induced desorption mass spectrometry was used to determine
      that the major protein in the purified enzyme is composed of similar or identical
      subunits of M(r) 58,119 Da. The native enzyme emerges with an apparent M(r) of
      174,000 Da from a gel permeation chromatography column. While this enzyme
      catalyzes the formation of conjugated trienes from a variety of polyunsaturated
      fatty acid precursors [arachidonate ((5Z,8Z,11Z,14Z)- eicosatetraenoate) is
      converted to (5Z,7E,9E,14Z)-eicosatetraenoate; gamma-linolenate ((6Z,9Z,12Z)
      octadecatrienoate) is converted to 6Z,8E,-10E-octadecatrienoate], this occurs
      most rapidly with eicosapentaenoate [(5Z,7E,9E,14Z,17Z)- eicosapentaenoate],
      which is likely the native substrate. Through a series of experiments utilizing
      gamma-linolenates stereospecifically labeled with deuterium, we have determined
      that the enzyme intramolecularly transfers the bis-allylic pro-S hydrogen from
      the C11 position to the C13 position. Furthermore, the bis-allylic pro-R hydrogen
      at C8 in gamma-linolenate is lost to the solvent. Using arachidonate as
      substrate, we demonstrated that the C11 olefinic position becomes protonated by a
      solvent-derived proton. There appears to be no requirement for molecular oxygen,
      and the transformation is catalyzed by this single enzyme.

PMID- 7803385
TI  - Functional characterization of human carbonic anhydrase II variants with altered
      zinc binding sites.
AB  - Carbonic anhydrase II (CAII) contains a conserved His3 zinc polyhedron which is
      essential for catalysis. Removal of any one of the His ligands by replacement
      with Ala decreases (approximately 10(5)-fold), but does not abolish, zinc binding
      and increases the rate constant for zinc dissociation. CAII variants with a His
      ligand substituted with Cys, Asp, or Glu bind zinc only approximately 10-fold
      better than a His2 zinc polyhedron in CAII. The large decrease in zinc affinity
      (approximately 5 kcal/mol) in these variants compared to the wild-type His3 site
      reflects mainly unfavorable compensatory protein structural rearrangements
      observed in the X-ray crystallographic structures of some of these CAII variants,
      described by Ippolito and Christianson (following paper in this issue). However,
      the zinc affinity of these sites is still higher than zinc polyhedra designed de
      novo. Substitution of the His zinc ligands with negatively charged amino acids
      both increases the pKa of the zinc-bound water by > or = 1.6 pH units, confirming
      that neutral ligands maintain the low zinc-water pKa, and decreases the pH
      independent kcat/KM for ester hydrolysis (3-30-fold) and CO2 hydration
      (approximately 10(3)-10(5)-fold). Additionally, decreases in the dissociation
      constant (approximately approximately 10(2)-10(5)-fold) for the transition state
      analog acetazolamide correlate with the decreased catalytic efficiency and
      increased pKa of these CAII variants. These data indicate that the histidine
      ligands, although not essential for catalysis, are conserved to maximize
      electrostatic stabilization of both the ground-state zinc-hydroxide and the
      negatively charged transition state. These studies provide valuable insights into
      the functional consequences of engineering a catalytic zinc site in a
      metalloenzyme.

PMID- 7803386
TI  - Structural consequences of redesigning a protein-zinc binding site.
AB  - In order to probe the structural importance of zinc ligands in the active site of
      human carbonic anhydrase II (CAII), we have determined the three-dimensional
      structures of H94C (in metal-bound form), H94C-BME (i.e., disulfide-linked with
      beta-mercaptoethanol), H94A, H96C, H119C, and H119D variants of CAII by X-ray
      crystallographic methods at resolutions of 2.2, 2.35, 2.25, 2.3, 2.2, and 2.25 A,
      respectively. Each variant crystallizes isomorphously with the wild-type enzyme,
      in which zinc is tetrahedrally coordinated by H94, H96, H119, and hydroxide ion.
      The structure of H94C CAII reveals the successful substitution of the naturally
      occurring histidine zinc ligand by a cysteine thiolate, and metal coordination by
      C94 is facilitated by the plastic structural response of the beta-sheet
      superstructure. Importantly, the resulting structure represents the catalytically
      active form of the enzyme reported previously [Alexander, R. S., Kiefer, L. L.,
      Fierke, C. A., & Christianson, D. W. (1993) Biochemistry 32, 1510-1518].
      Contrastingly, the structure of H96C CAII reveals that the engineered side chain
      does not coordinate to zinc; instead, zinc is tetrahedrally liganded by H94,
      H119, and two solvent molecules. Thus, the beta-sheet superstructure is not
      sufficiently plastic in this location to allow C96 to coordinate to the metal
      ion. Substitution of the thiolate or carboxylate group for wild-type histidine in
      H119C and H119D CAIIs reveals that tetrahedral metal coordination is maintained
      in each variant; however, since there is no plastic structural response of the
      corresponding beta-strand, a longer metal-ligand separation results.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7803387
TI  - Development of nonpolar surfaces in the folding of Escherichia coli dihydrofolate
      reductase detected by 1-anilinonaphthalene-8-sulfonate binding.
AB  - The development of nonpolar surfaces during the folding of Escherichia coli
      dihydrofolate reductase (DHFR) was studied by monitoring the time-dependent
      fluorescence of 1-anilinonaphthalene-8-sulfonate (ANS) included in the refolding
      solution. Stopped-flow refolding experiments demonstrated a rapid increase in
      fluorescence intensity within the dead time of mixing (5 ms), indicating that the
      earliest detectable folding intermediate contains hydrophobic surfaces which are
      capable of binding ANS. A further increase in fluorescence intensity over the
      next 300 ms coincides with the formation of a set of four intermediates which are
      known to contain a specific tertiary contact [Kuwajima, K., Garvey, E. P., Finn,
      B. E., Matthews, C. R., & Sugai, S. (1991) Biochemistry 30, 7693-7703].
      Experiments performed in the presence of polar fluorescence quenching agents
      indicate that the binding sites for ANS in the burst phase species are more
      exposed to solvent than those in the subsequent set of intermediates. When
      considered along with the above study of the formation of secondary structure by
      stopped-flow circular dichroism, these results imply that DHFR initially forms a
      molten globule intermediate. Subdomains containing specific tertiary structure
      and more solvent-excluded ANS binding sites then form before ultimately being
      converted to native or native-like conformations during the rate-limiting steps
      in the folding of DHFR. The occurrence of similar kinetic phases observed by ANS
      binding during the folding of a number of other proteins suggests that this may
      be a common scheme for protein folding reactions.

PMID- 7803388
TI  - Drug binding by calmodulin: crystal structure of a calmodulin-trifluoperazine
      complex.
AB  - The crystal structure of calmodulin (CaM) bound to trifluoperazine (TFP) has been
      determined and refined to a resolution of 2.45 A. Only one TFP is bound to CaM,
      but that is sufficient to cause distortion of the central alpha-helix and
      juxtaposition of the N- and C-terminal domains similar to that seen in CaM
      polypeptide complexes. The drug makes extensive contacts with residues in the C
      terminal domain of CaM but only a few contacts with one residue in the N-terminal
      domain. The structure suggests that substrate binding to the C-terminal domain is
      sufficient to cause the conformational changes in calmodulin that lead to
      activation of its targets.

PMID- 7803389
TI  - The Cys(X)5Arg catalytic motif in phosphoester hydrolysis.
AB  - The Yersinia protein tyrosine phosphatase (PTPase) was identified in the genus of
      bacteria responsible for the plague or the Black Death and was shown to be
      essential for pathogenesis. The three-dimensional structure of the catalytic
      domain of the Yersinia PTPase has been solved, and this information along with a
      detailed kinetic analysis has led to a better understanding of the catalytic
      mechanism of the PTPase. Mutational and chemical modification experiments have
      established that an invariant Cys residue (Cys403) is directly involved in
      formation of a covalent phosphoenzyme intermediate. We have shown that Arg409
      plays a critical role in PTPase action and that the Cys(X)5Arg active site motif
      forms a phosphate-binding loop which appears to represent the essential features
      necessary for catalysis by the PTPases, the dual specific phosphatases, and the
      low molecular weight acid phosphatases.

PMID- 7803390
TI  - Structural consequences of histidine phosphorylation: NMR characterization of the
      phosphohistidine form of histidine-containing protein from Bacillus subtilis and
      Escherichia coli.
AB  - The bacterial phosphoenolpyruvate:sugar phosphotransferase system involves a
      series of reactions in which phosphoprotein intermediates are formed. Histidine
      containing protein (HPr) is phosphorylated on the N delta 1 position of the
      imidazole ring of His15 by enzyme I and acts as a phosphoryl donor to the sugar
      specific enzymes IIA. The structure of phosphorylated HPr from Bacillus subtilis,
      primarily, and from Escherichia coli has been studied by nuclear magnetic
      resonance (NMR) spectroscopy. Phosphorylation of His15 results in large downfield
      shifts in amide proton and nitrogen resonances for residues 16 and 17 but results
      in only modest or no shifts in other backbone resonances. The exchange rates of
      these two amide groups are decreased more than 10-fold upon phosphorylation.
      Analysis of the coupling constants 3JNH alpha revealed no significant changes
      throughout the protein, indicating that backbone phi dihedral angles do not
      change detectably. 3J alpha beta and 3JN beta patterns determined from P.E.COSY
      and HNHB spectra, respectively, revealed a change in one side chain, that of
      conserved Arg17. Analysis of NOESY spectra revealed a limited number of changes
      in NOEs involving protons in Ser12, His15, Arg71, and Pro18 in B. subtilis HPr.
      The NMR results indicate that the Arg17 side chain becomes limited in its
      conformational range in the phosphorylated protein, taking on a conformation that
      points its guanidinium group toward the phosphoryl group on His15. In addition,
      the tautomeric and ionization states of His15 have been determined using 15N and
      31P NMR. At neutral pH, the imidazole is predominantly in the protonated form and
      the phosphoryl group is in the dianionic form in P-His15. Altogether, the results
      indicate that phosphorylation of His15 yields only a local effect on the
      protein's structure. The data are consistent with a small change in the
      disposition of the histidine side chain, allowing phosphoryl group oxygens to
      serve as hydrogen bond acceptors for the amide protons of residues Ala16 and
      Arg17, which constitute the first two residues of an alpha-helix. Thus, similar
      to many proteins that bind phosphoryl moieties noncovalently, the phosphoryl
      group in P-His15-HPr is situated to allow for a favorable electrostatic
      interaction at the N-terminal end of an alpha-helix.

PMID- 7803391
TI  - Interaction of transforming growth factor alpha with the epidermal growth factor
      receptor: binding kinetics and differential mobility within the bound TGF-alpha.
AB  - The interaction of transforming growth factor alpha (TGF-alpha) with the complete
      extracellular domain of the epidermal growth factor receptor (EGFR-ED) was
      examined by nuclear magnetic resonance (NMR) spectroscopy. The 1H NMR resonances
      of the methyl groups of TGF-alpha were used as probes of the interaction of TGF
      alpha with the EGF receptor to determine the binding kinetics and the
      differential mobility within the bound TGF-alpha. The methyl resonances were
      studied because there are 14 methyl containing residues well dispersed throughout
      the structure of TGF-alpha and the relaxation properties of methyl groups are
      well understood. Changes in the longitudinal and transverse 1H NMR relaxation
      rates of the methyl resonances of TGF-alpha caused by binding to the 85-kDa EGFR
      ED were studied. From these measurements it was determined that the interaction
      was in the NMR fast exchange limit. A binding mechanism to rationalize the
      different rates determined by NMR and surface plasmon resonance techniques [Zhou,
      M., et al. (1993) Biochemistry 32, 8193-8198] is proposed. The transverse
      relaxation rate (R2) enhancements of the various methyl resonances displayed a
      regional dependence within the bound TGF-alpha molecule. Resonances from the C
      terminus of TGF-alpha, which were flexible in the unbound molecule, revealed
      dramatic increases in their R2 upon binding to the EGFR-ED along with resonances
      from the interior of TGF-alpha. However, upon binding, the R2 enhancements of the
      methyl resonances from the N-terminus of TGF-alpha, which were also flexible in
      the unbound TGF-alpha, were slight; indicating a retention of mobility of this
      region for bound TGF-alpha. The implications of these data with respect to the
      mechanism of receptor activation and the design of antagonists are discussed.

PMID- 7803392
TI  - Effect of temperature and host factors on the activities of pertussis toxin and
      Bordetella adenylate cyclase.
AB  - Pertussis toxin and adenylate cyclase toxin both contribute to the pathogenesis
      of whooping cough. Production of these proteins is controlled by the bvg locus,
      which is inactive at 25 degrees C, but at 37 degrees C produces a Vir+ phenotype.
      In view of the temperature dependence of virulence factor synthesis, the effects
      of temperature and host factors on their action were examined. The NAD
      glycohydrolase activity of the S1 subunit of pertussis toxin was enhanced by
      CHAPS, a zwitterionic detergent, with a temperature optimum of approximately 35
      degrees C. Similar temperature optima for the ADP-ribosylation by pertussis toxin
      of transducin and recombinant Go alpha were observed. Since the temperature-
      activity relationship of S1 differed from that of S1 in activated holotoxin, and
      since S1 in activated holotoxin was more stable at 42 degrees C than was S1, it
      appears that S1 associated with the B oligomer components may, in fact, be an
      active species. Bordetella pertussis adenylate cyclase is activated by a host
      factor, calmodulin. In the absence of calmodulin, the temperature optimum for
      enzymatic activity was approximately 25 degrees C, whereas in its presence it was
      approximately 35 degrees C. Thus, the temperature optima for pertussis and
      adenylate cyclase toxins, virulence factors whose production is increased through
      the bvg locus at physiological temperatures, are either at or near these
      temperatures when stimulated by host factors.

PMID- 7803393
TI  - Structural changes caused by site-directed mutagenesis of tyrosine-98 in
      Desulfovibrio vulgaris flavodoxin delineated by 1H and 15N NMR spectroscopy:
      implications for redox potential modulation.
AB  - Flavodoxins mediate electron transfer at low redox potential between the
      prosthetic groups of other proteins. Interactions between the protein and the
      flavin mononucleotide cofactor shift both the oxidized/semiquinone and
      semiquinone/hydroquinone redox potentials significantly from their free-in
      solution values. In order to investigate the possible role that the tyrosine at
      position 98 plays in this process, we have used heteronuclear three-dimensional
      NMR spectroscopy to determine the solution conformation of wild-type and four
      position-98 mutants, Y98W, Y98H, Y98A, and Y98R, of Desulfovibrio vulgaris
      flavodoxin. Assigned 1H and 15N resonances indicate that the secondary structure
      and topology of the proteins are identical. However, residues that undergo
      substantial mutation-induced changes in chemical shift are spread throughout the
      flavin cofactor binding site. Distance and dihedral angle constraints were used
      to generate solution structures for the wild-type and mutant proteins.
      Collectively, the mutant proteins have no gross conformational changes in the
      flavin binding site. The changes that do occur are minor and result from the
      different packing interactions required to accommodate the new side chain at
      position-98. The solvent accessibility and electrostatic nature of the flavin
      binding site in the mutant proteins are compared to those of the wild-type
      structure. The structural data support the hypothesis that the very low midpoint
      of the semiquinone/hydroquinone couple in the wild-type protein is modulated to a
      large extent by the energetically unfavorable formation of the flavin
      hydroquinone anion in the apolar environment of the flavin binding site.

PMID- 7803394
TI  - Heterodimerization of the yeast homeodomain transcriptional regulators alpha 2
      and a1: secondary structure determination of the a1 homeodomain and changes
      produced by alpha 2 interactions.
AB  - The homeodomain proteins, a1 and alpha 2, act cooperatively to regulate cell-type
      specific genes in yeast. The basis of this cooperativity is an interaction
      between the two proteins, forming a heterodimer that binds DNA tightly and
      specifically. A fragment containing the homeodomain of a1, a1(66-126), has been
      studied by NMR spectroscopy to gain secondary structure information and to
      characterize the changes in a1 upon heterodimerization with alpha 2.
      Heteronuclear (1H-15N) NMR methods were used to assign backbone resonances of the
      61 amino acid fragment. The a1(66-126) secondary structure was determined using
      NOE connectivities, 3JHN alpha coupling constants and hydrogen exchange kinetic
      data. NMR data identify three helical segments separated by a loop and a tight
      turn that are the characteristic structural elements of homeodomain proteins. The
      a1 fragment was titrated with alpha 2(128-210), the homeodomain-containing
      fragment of alpha 2, to study changes in a1(66-126) spectra produced by alpha 2
      binding. The a1(66-126) protein was labeled with 15N and selectively observed
      using isotope-edited NMR experiments. NMR spectra of bound a1(66-126) indicate
      that residues in helix 1, helix 2, and the loop connecting them are directly
      involved in the binding of the alpha 2 fragment. Relatively minor effects on the
      resonances from residues in helix 3, the putative DNA-binding helix, were noted
      upon alpha 2 binding. We have thus located a region of the a1 homeodomain
      important for specific protein recognition.

PMID- 7803395
TI  - Fluorescence energy transfer between two triple helix-forming oligonucleotides
      bound to duplex DNA.
AB  - An 11-mer oligopyrimidine was covalently linked via its 5'-phosphate to an
      acridine derivative (acridine-11-mer), and a 13-mer was covalently linked via its
      3'-phosphate to an ethidium derivative (13-mer-ethidium). Each of them formed a
      triple helix with a 31-bp DNA fragment containing two oligopurine-oligopyrimidine
      sequences, 11 and 13 bp in length, separated by a variable number of base pairs.
      When both oligonucleotides were bound to the 31-bp DNA fragment, fluorescence
      energy transfer (FET) from acridine to ethidium was observed, as revealed by a
      quenching of acridine fluorescence and a sensitized ethidium emission. FET was
      temperature-dependent and occurred only when both oligonucleotides were
      simultaneously bound to the DNA matrix. A single base-pair change in one of the
      target sequences strongly reduced the energy-transfer efficiency. This method was
      used to discriminate between a fully complementary and a mismatched target
      sequence.

PMID- 7803396
TI  - Direct measurement of thermodynamic and kinetic parameters of DNA triple helix
      formation by fluorescence spectroscopy.
AB  - Direct measurement of thermodynamic and kinetic parameters of oligonucleotide
      directed DNA triple helix formation has been achieved by fluorescence
      spectroscopic methods. Fluorescence resonance energy transfer (FRET) was used to
      study the binding of an acceptor-labeled single-stranded oligonucleotide to a
      donor-labeled DNA duplex. Equilibrium binding constants and association rate
      constants for triplex formation between 5'-tetramethylrhodamine-labeled 11-mer,
      13-mer, and 15-mer homopyrimidine oligonucleotides and a 5'-fluorescein-labeled,
      25-bp DNA duplex containing a 15-bp homopurine site were determined by FRET
      measurements, and the values were in close agreement with those determined by
      established methods. The thermal dissociation profile of the triplex-to-duplex
      transition was also directly observed by FRET and was consistent with the triplex
      melting curves obtained by UV absorbance measurements. In addition, a homogeneous
      fluorescence anisotropy assay is described which enables determination of the
      binding constants between 5'-tetramethylrhodamine-labeled 11-mer and 13-mer
      homopyrimidine oligonucleotides and unlabeled 25-, 30-, and 50-bp double-stranded
      DNA containing a homopurine target site. These results demonstrate the utility of
      nonradioactive fluorescence measurements as an efficient method for studying
      triple helix formation under homogeneous solution conditions and highlight the
      uniqueness of the FRET method for obtaining equilibrium, kinetic, and thermal
      dissociation data in a straightforward manner.

PMID- 7803397
TI  - Effect of a triplex-binding ligand on parallel and antiparallel DNA triple
      helices using short unmodified and acridine-linked oligonucleotides.
AB  - We have used DNase I footprinting to investigate the effect of a triplex-binding
      ligand on the formation of intermolecular DNA triple helices at target sites that
      have been cloned into longer DNA fragments. In the presence of a triplex-binding
      ligand (N-[2-(dimethylamino)ethyl]-2-(2-naphthyl)quinolin-4-ylamine ), the
      concentrations of T5C5 and C5T5 required to generate DNase I footprints at the
      target sites A6G6.C6T6 and G6A6.T6C6, respectively, are reduced by at least 100
      fold. Complexes with the acridine-linked oligonucleotides Acr-T5C5 and Acr-C5T5
      are stabilized to a much lesser extent and produce footprints at concentrations
      similar to those of the unmodified oligonucleotides in the presence of the
      ligand. The stabilizing effects of acridine modification or the addition of a
      triplex-binding ligand are not additive. The position and length of the
      footprints produced by Acr-T5C5 and T5C5 at the target sequence A6G6.C6T6 are
      unaffected by the ligand. In contrast, footprints at the target site G6A6.T6C6
      appear 3-4 bases shorter in the presence of the ligand, when viewed from the
      pyrimidine strand, and 1-2 bases longer on the purine strand. These results are
      explained by suggesting that the compound binds at T.AT triplets and prevents the
      transmission of any DNA structural changes into the flanking duplex. The compound
      has a smaller stabilizing effect on short antiparallel triplexes consisting of
      G.GC and T.AT triplets. Binding of Acr-G5T5 to A6G6.C6T6 is enhanced slightly by
      the compound, which increases the apparent footprinting site, probably by
      preventing fraying at the 3'-end of the third strand. The compound does not
      promote the binding of G5T5 to A6G6.C6T6 or that of Acr-T5G5 and T5G5 to
      G6A6.T6C6.

PMID- 7803398
TI  - Reaction of a biscationic distamycin-ellipticine hybrid ligand with DNA. Mode and
      sequence specificity of binding.
AB  - Molecular modeling of complexes between the octanucleotide d(CGATATCG)2 and
      either a monocationic or biscationic distamycin-ellipticine hybrid molecule
      predicted that the extra positive charge on the latter conjugate ligand should
      ensure tight fitting into the minor groove of the duplex without affecting
      intercalation of the ellipticine chromophore. To test this prediction, we have
      synthesized a biscationic compound Distel (2+) and investigated its interaction
      with DNA using various optical and gel electrophoresis techniques. Viscosity,
      fluorescence lifetime, and circular and linear dichroism measurements bear out
      the validity of the calculations and show that Distel (2+) does indeed come to
      lie with its distamycin moiety in the minor groove of DNA and its ellipticine
      ring intercalated nearby. Linear dichroism experiments with a range of
      polynucleotides indicate that, unlike its monocationic homologue, the biscationic
      ligand engages in bidentate binding to AT sequences but not to GC sequences.
      Footprinting studies employing DNase I and methidiumpropyl-EDTA.FeII as DNA
      cleaving agents reveal that the biscationic hybrid is notably selective for AT
      rich sequences in DNA. The concentrations required to detect a clear footprint at
      AT sites with Distel (2+) are 4- to 10-fold lower than those required to produce
      comparable DNase I footprints with distamycin alone. Also, in accord with the
      energy-minimized model of the hybrid-oligonucleotide complex, chemical probing
      experiments using diethyl pyrocarbonate and osmium tetroxide reveal that the
      hybrid causes significant distortion of the DNA helix, explicable in terms of
      bending of the duplex toward the minor groove, which greatly enhances the
      reactivity toward probes in the major groove of the DNA. The experimental results
      help to identify the determinant factors, predominantly steric and electrostatic
      interactions, which shape the DNA-binding reaction. Thus, molecular modeling has
      correctly predicted the DNA-binding properties of a doubly charged ligand and
      shown that appending an auxiliary basic group onto the distamycin moiety was the
      right way to proceed in order to convert a nonspecific conjugate into a highly
      specific DNA reader.

PMID- 7803399
TI  - Differences in the protease activities of tetanus and botulinum B toxins revealed
      by the cleavage of vesicle-associated membrane protein and various sized
      fragments.
AB  - Botulinum neurotoxin serotype B (BoNT/B) and tetanus toxin (TeTx) block
      neuroexocytosis through selective endoproteolysis of vesicle-associated membrane
      protein (VAMP). The enzymological properties of both toxins were compared for the
      first time in their cleavage of VAMP and various sized fragments using a
      sensitive chromatographic assay. The optimal substrate sizes for the zinc
      dependent protease activities of the light chains of TeTx and BoNT/B were
      established using synthetic peptides corresponding to the hydrophilic core of
      VAMP (30-62 amino acids in length). TeTx was found to selectively cleave the
      largest peptide at a single site, Gln76-Phe77. It exhibited the most demanding
      specificity, requiring the entire hydrophilic domain (a 62-mer) for notable
      hydrolysis, whereas BoNT/B efficiently cleaved the much smaller 40-mer. Thus, an
      unusually long N-terminal sequence of 44 amino acids upstream of the scissile
      bond is required for the selective hydrolysis of VAMP by TeTx. Using the largest
      peptide, BoNT/B and TeTx exhibited approximately 50% and 35%, respectively, of
      the activities shown toward intact VAMP, detergent solubilized from synaptic
      vesicles. Given the large size of the smallest substrates, it is possible that
      these neurotoxins recognize and require a three-dimensional structure. Although
      both toxins were inactivated by divalent metal chelators, neither was antagonized
      by phosphoramidon or ASQFETS (a substrate-related peptide that spans the cleavage
      site), and TeTx was only feebly inhibited by captopril; also, they were
      distinguishable in their relative activities at different pHs, temperatures, and
      ionic strengths. These collective findings are important in the design of
      effective inhibitors for both toxins, as well as in raising the possibility that
      TeTx and BoNT/B interact somewhat differently with VAMP.

PMID- 7803400
TI  - A hydrophobic inhibitor of the nicotinic acetylcholine receptor acts on the
      resting state.
AB  - 3-(Trifluoromethyl)-3-(m-iodophenyl)diazirine (TID) has recently been found to be
      a noncompetitive inhibitor of the nicotinic acetylcholine receptor (nAcChoR) by
      both photolabeling and flux assays (White et al., 1991). However, these
      experiments were done when TID was in equilibrium with the nAcChoR, and thus only
      its interactions with the resting and the desensitized states of the nAcChoR were
      studied. In this work we characterized the interaction between TID and nAcChoR in
      the open and resting states using a flux assay. When TID and acetylcholine were
      simultaneously mixed with the nAcChoR in native Torpedo vesicles, TID did not
      inhibit agonist-induced 86Rb+ flux. However, following prolonged preincubation (4
      min) of TID with nAcChoR, complete inhibition was observed with a half-inhibition
      constant of 0.4 microM TID and a Hill coefficient of 0.9. This suggested that TID
      might act either on the resting or the desensitized state in preference to the
      open state of the nAcChoR. Preincubation of nAcChoR with TID, followed by a 7 ms
      agonist-induced flux assay, showed that the flux response declined exponentially
      with preincubation time. Assuming a pseudo-first-order process, analysis revealed
      the rate constant for the onset of inhibition of nAcChoR in the resting state to
      be in the range of (1.2-3.4) x 10(6) M-1 s-1. To test if fast desensitization was
      enhanced by TID under these conditions, we used a fluorescent analog of
      acetylcholine. Stopped-flow fluorimetry showed that the fraction of nAcChoR in
      the predesensitized state did not increase during preincubation with
      TID.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7803401
TI  - Identification of two classes of lipid molecule binding sites on the microsomal
      triglyceride transfer protein.
AB  - The gene for the microsomal triglyceride transfer protein (MTP) is defective in
      subjects with the genetic disease abetalipoproteinemia, indicating that MTP is
      essential for the assembly of apolipoprotein B containing lipoproteins. In vitro,
      MTP is a lipid molecule binding protein that catalyzes lipid transport between
      membranes by a shuttle mechanism. In this study, the lipid binding properties of
      MTP were examined. MTP was incubated with donor phosphatidylcholine vesicles of
      varying neutral lipid composition. MTP was subsequently reisolated by
      ultracentrifugation, and MTP-bound lipid was quantitated. When the triolein
      content of the vesicles was increased up to 4 mol %, neutral lipid binding to MTP
      increased proportionately, while phosphatidylcholine binding appeared to remain
      constant around two molecules per MTP. Using phosphatidylcholine emulsions
      containing 60 mol % triolein as the donor particles resulted in only a slight
      increase in triolein binding to MTP. The highest triolein:MTP ratio observed was
      (0.20-0.25):1. Differences in the neutral and phospholipid binding properties of
      MTP were observed by measuring the transport of lipid from MTP to acceptor
      vesicles. Transport of triolein was rapid and complete, while phosphatidylcholine
      transport was biphasic, containing rapid and slow phases. These results indicated
      that MTP contains more than one class of lipid molecule binding site.
      Measurements of fluorescent lipid transport from donor vesicles to MTP supported
      this hypothesis. The transport of pyrene-labeled triglyceride from donor
      particles to MTP was rapid, while phosphatidylcholine transfer had fast and slow
      phases. From these data, we propose that MTP contains at least two distinct
      classes of lipid molecule binding sites that differ in function. The fast site or
      sites are responsible for lipid transport.

PMID- 7803402
TI  - Polymerization of Antarctic fish tubulins at low temperatures: role of carboxy
      terminal domains.
AB  - We have proposed previously that the efficient polymerization of tubulins from
      Antarctic fishes at low, physiological temperatures (-1.8 to +2 degrees C) may
      result in part from adaptations (e.g., reductions in acidic residues) located in
      their carboxy-terminal (C-terminal) tails [Detrich & Overton (1986) J. Biol.
      Chem. 261, 10922-10930]. To test this hypothesis, we have examined the
      polymerization of Antarctic fish neural tubulins modified at their C termini by
      proteolysis or by neutralization of carboxyl groups. Addition of subtilisin to
      low concentrations of Notothenia coriiceps tubulin induced a biphasic assembly
      reaction: stage I corresponded to the C-terminal cleavage of beta chains to
      produce alpha beta s dimers, and stage II coincided with the slower, C-terminal
      cleavage of alpha chains to yield alpha s beta s. Both stage I and stage II
      polymers consisted of protofilament sheets and microtubules with attached sheets.
      The critical concentration for assembly of the stage II polymer was at least 10
      fold lower than that of untreated tubulin. Neutralization of Glu and Asp
      carboxyls in Gobionotothen gibberifrons microtubules by the carbodiimide
      catalyzed incorporation of glycine ethyl ester (GEE) moieties produced a tubulin,
      modified largely in its C termini, that assembled more readily than did control
      tubulin. When 12 GEE groups were incorporated per dimer, the critical
      concentrations for assembly of modified tubulin at 5-10 degrees C were 2-3-fold
      smaller than those for the unmodified protein. Comparably modified bovine tubulin
      (10 GEE/dimer) assembled at 37 degrees C with a critical concentration 2.6-fold
      lower than that for the unmodified tubulin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7803405
TI  - Backbone dynamics of a two-domain protein: 15N relaxation studies of the amino
      terminal fragment of urokinase-type plasminogen activator.
AB  - The amino-terminal fragment (ATF) of urokinase-type plasminogen activator (u-PA)
      is a two-domain protein which consists of a kringle and a growth factor domain
      (GFD). The dynamics of uniformly 15N-labeled ATF was examined by measuring the
      longitudinal (T1) and transverse (T2) 15N relaxation times and heteronuclear
      NOEs. The data were interpreted in terms of the model-independent spectral
      density function. The GFD was found to exhibit a high degree of anisotropy,
      whereas the kringle domain of ATF undergoes isotropic reorientation. This
      difference in anisotropy is best explained by the two domains moving
      independently such as differently shaped beads on a string. With the exception of
      the N- and C-terminal regions of the protein, the most flexible region of ATF was
      the seven-residue omega loop (N22-I28) of the GFD which has been implicated in
      the binding of u-PA to its receptor. The amides of the linker region between the
      domains displayed high values of the order parameter, indicating restricted
      motion on the picosecond time scale. This is in contrast to the flexible linker
      of calmodulin [Barbato et al. (1992) Biochemistry 31, 5269-5278], which displayed
      low values of S2 and unrestricted motion in the linker region.

PMID- 7803403
TI  - Solution structure of PMP-D2, a 35-residue peptide isolated from the insect
      Locusta migratoria.
AB  - The three-dimensional solution structure of PMP-D2, a 35 amino acid peptide
      isolated from the insect Locusta migratoria, has been determined from two
      dimensional 1H NMR spectroscopy data. The structure calculations were performed
      from 222 NOE-derived interproton distances and 11 dihedral angles calculated from
      the JHN-H alpha coupling constants, using either a combination of distance
      geometry and restrained simulated annealing or by restrained simulated annealing
      alone. PMP-D2 contains three disulfide bridges that have been assigned from NMR
      data and structure calculations and independently confirmed using chemical and
      enzymatic methods. The core region of PMP-D2 adopts a compact globular fold,
      stabilized by hydrophobic interactions, which consists of a short three-stranded
      antiparallel beta-sheet involving residues 8-11, 15-19, and 25-29. Back
      calculation of the NOESY spectra was used to validate the final structures.
      Analysis of the CD spectra of PMP-D2 under various conditions of ionic strength
      and in the presence of organic solvents demonstrates the high stability of this
      molecule. PMP-D2 was recently shown to inhibit Ca2+ currents. This activity is
      discussed based on the comparison of PMP-D2 three-dimensional structure with the
      recently established three-dimensional structure of the Ca2+ channel blocker
      omega-conotoxin GVIA.

PMID- 7803404
TI  - Crystal structure of the ferredoxin I from Desulfovibrio africanus at 2.3 A
      resolution.
AB  - The crystal structure of the ferredoxin I from the sulfate-reducing bacterium
      Desulfovibrio africanus (DaFdI) has been solved and refined by X-ray diffraction.
      The crystals are orthorhombic with a = 96.6 A, b = 58.1 A, and c = 20.7 A, space
      group P2(1)2(1)2, and two ferredoxin molecules per asymmetric unit. The initial
      electron density map has been obtained by combining phasing by molecular
      replacement methods, anomalous scattering, and noncrystallographic averaging. The
      final crystallographic R factor is 0.182 with 10-2.3 A resolution data. In
      parallel, the amino acid sequence was redetermined. This showed that DaFdI
      contains 64 residues (instead of 61) including one free cysteine, one histidine,
      and one tryptophan in the C-terminal part of the molecule. The current molecular
      model includes the two molecules of the asymmetric unit, 67 water molecules, and
      one sulfate ion. The DaFdI overall folding very closely resembles that of
      ferredoxins of known structure. Comparisons with the single cluster ferredoxins
      from Desulfovibrio gigas and Bacillus thermoproteolyticus show that the presence
      or the absence of a disulfide bridge does not significantly affect the folding of
      the other half of the molecule, including the characteristic alpha-helix of the
      single cluster ferreddoxins. Like other ferredoxins or analogs, the [4Fe-4S] iron
      -sulfur cluster presents, at 2.3 A resolution, a cubane-like geometry. By
      contrast, its immediate environment is different as it includes, besides the four
      cysteic sulfur ligands, the sulfur atom of the free cysteine. This sulfur atom,
      which is buried within the protein, is in van der Waals contact with one labile
      sulfur of the cluster and one liganded cysteic sulfur. The association of a [4Fe
      4S] cluster with one free cysteic sulfur is similar to that previously found in
      both X-ray structures of Azotobacter vinelandii and Peptococcus aerogenes [Stout,
      C. D. (1989) J. Mol. Biol. 205, 545-555; Backes, G., et al. (1991) J. Am. Chem.
      Soc. 113, 2055-2064]. Chemical sequence analysis suggests that this
      characteristic [4Fe-4S] cluster sulfur environment is widely distributed among
      ferredoxins.

PMID- 7803406
TI  - Resonance Raman study of the active site of Coprinus cinereus peroxidase.
AB  - Resonance Raman (RR) spectra for the resting state ferric and the reduced ferrous
      forms of recombinant Coprinus cinereus peroxidase (CIP), obtained with different
      excitation wavelengths and in polarized light, are reported. The spectra are
      compared with those obtained previously for cytochrome c peroxidase expressed in
      Escherichia coli [(CCP(MI)] and horseradish peroxidase (HRP-C). Although the
      enzymic properties of CIP and HRP-C are similar, the RR data show that, in terms
      of the heme cavity structures, CIP and CCP(MI) are much more closely related to
      each other than to HRP-C. The ferric state of CIP at neutral pH is characteristic
      mainly of a five-coordinate high spin heme. However, the lower frequency of the
      v2 mode and a higher frequency of the v(C = C) vinyl stretching modes for CIP as
      compared to CCP, indicate a higher degree of vibrational coupling between the two
      modes in CIP. In addition, CIP is rather unstable under low laser power
      irradiation as an irreversible transition to a six-coordinate high spin heme
      followed by a second transition to a six-coordinate low spin heme is observed.
      This instability of CIP as compared to CCP(MI) is proposed to be a consequence of
      the presence of a distal Phe54 in CIP rather than the homologous Trp51 in CCP, as
      Trp51 is hydrogen-bonded to a distal water molecule located above the heme Fe
      thereby preventing its coordination in CCP. In CIP the FeII-His RR band has two
      components with frequencies at 230 and 211 cm-1.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7803407
TI  - Protein coordination to manganese determines the high catalytic rate of
      dimanganese catalases. Comparison to functional catalase mimics.
AB  - Catalysis of hydrogen peroxide dismutation by the dimanganese catalase from
      Thermus thermophilus has been measured and found to obey Michaelis-Menton
      kinetics with no evidence for substrate inhibition at concentrations up to 0.45 M
      H2O2. Comparison among three dimanganese catalases (Thermus thermophilus,
      Thermoleophilium album, and Lactobacillus plantarum) reveals that their apparent
      second-order rate constants, Kcat/Km, differ by at most a factor of 5, even
      though the individual kinetic constants differ by as much as a factor of 20. This
      similarity suggests that all three enzymes may have the same rate-determining
      step. For T. thermophilus catalase we find that kcat/Km approximately kbi, the
      bimolecular rate constant at limiting substrate concentrations. Thus, the rate of
      the rate-determining step is unaltered over the entire range of substrate
      concentrations, unlike T. album and L. plantarum catalases where substrate
      inhibition has been reported. Comparison to structurally characterized
      dimanganese complexes and dimetalloproteins (arginase, hemerythrin), which are
      functional, albeit kinetically slow, catalase mimics, reveals that high catalase
      activity correlates with a greater number of stronger sigma-ligand donors like
      anionic carboxylatos vs neutral histidines that stabilize the oxidized
      Mn2(III,III) state over reduced Mn2(II,II). A critical feature for enzymatic
      functionality in vivo is suppression of one-electron chemistry leading to
      formation of the mixed-valence forms, Mn2(III,IV) and Mn2(II,III), which are
      kinetically inactive or precursors to inactive species, respectively. Evidence is
      presented from model compounds suggesting that the mu-carboxylato bridge between
      Mn ions in catalase may play the key role in suppressing formation of these
      detrimental oxidation states through destabilization of these one-electron redox
      processes.

PMID- 7803408
TI  - Resonance Raman investigation of imidazole and imidazolate complexes of
      microperoxidase: characterization of the bis(histidine) axial ligation in c-type
      cytochromes.
AB  - In order to evaluate the steric and electronic influences of the heme axial
      ligands on the vibrational modes of heme c, various ferric and ferrous six
      coordinate heme c compounds have been prepared from microperoxidase-8 (MP8) and
      different extrinsic ligands. In this paper, the absorption and Soret-excited
      resonance Raman (RR) spectra of imidazole, imidazolate, 1-methylimidazole, and
      histidine complexes of MP8 are presented. The absorption characteristics of the
      unligated forms, either aggregated or monomeric, as well as of the ligated forms
      of MP8(III) and MP8(II) have been determined as a function of pH, the presence of
      a cationic detergent, and the ligand concentration. Spectrophotometric titrations
      have shown that MP8(III) and MP8(II) can bind one or two molecules of exogenous
      ligand, forming monoligated or bisligated complexes. The latter form, observed
      with large excesses of ligand, results from the displacement of the intrinsic
      proximal His of MP8 by an exogenous ligand. Several structural marker bands have
      been detected in the high- and low-frequency regions of RR spectra. The high
      frequency RR spectra of the ImH compounds of MP8(III) exhibit a v10 mode
      sensitive to ligand deprotonation(s). Moreover, the replacement of His by an
      exogenous ImH in MP8(III) complexes induces the upshift of the v10 mode frequency
      (1637-1641 cm-1), indicating that the porphyrin skeleton is less distorted when
      the internal coordination of proximal His to heme is broken. A similar dependence
      of the out-of-plane porphyrin distortion is suggested for the low-frequency mode
      v8 (343-347 cm-1). As far as the ferrous compounds are concerned, the mode most
      sensitive to the ImH deprotonation is v11, which is downshifted from 1539 to 1527
      cm-1. Comparisons of the low-frequency regions of the RR spectra of imidazole
      type ligated MP8(III) and MP8(II) complexes, as well as observations based on
      isotopic substitutions of the corresponding 1-methylimidazole complexes (MeIm-
      >MeIm-d6), allow the assignment of two bands in the 184-197 and 400-409 cm-1
      regions to modes involving the symmetric and asymmetric stretches of the axial
      ligands, respectively. Two other bands in the 343-347 and 359-362 cm-1 regions,
      sensitive to the mass and/or deprotonation states of the axial ligands, have been
      tentatively assigned to v(Fe-N(pyrrole)) modes coupled to either a deformation
      mode of axial bonds or an internal mode of the bound imidazole(s).(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7803409
TI  - Vaccinia DNA topoisomerase I: kinetic evidence for general acid-base catalysis
      and a conformational step.
AB  - The pH dependences of the internal equilibrium (Kcl) and rate constants for site
      specific DNA strand cleavage (kcl) and resealing (kr) catalyzed by Vaccinia DNA
      topoisomerase I have been investigated using single-turnover conditions in the pH
      range 4.6-9.8 at 20 degrees C. The pH dependence of the rate constant for strand
      cleavage (kcl) shows a bell-shaped profile with apparent pKa values of 6.3 +/-
      0.2 and 8.4 +/- 0.2, suggesting base catalysis of the attack of the active site
      Tyr-274 on the phosphodiester phosphorus, and acid catalysis of the expulsion of
      the 5'-deoxyribose oxygen. A low pKa (i.e., 6.3) for Tyr-274 in the free enzyme
      is ruled out by NMR titration from pH 5.1 to 8.8 monitoring the C-zeta chemical
      shift of [zeta-13C]-tyrosine-enriched topoisomerase. The dependence of the
      internal equilibrium constant (Kcl) on pH reveals very similar pKa values as kcl
      (5.8 +/- 0.2 and 8.6 +/- 0.2). However, kr is found to be independent of pH. The
      differing response of kcl and kr to pH rules out a simple two-state internal
      cleavage equilibrium and suggests that a conformational change occurs following
      formation of the covalent complex which retains the correct protonation state for
      strand religation. A conformation step is further indicated by a 4.6-fold "thio
      effect" on kcl upon substitution of the nonbridging oxygen atom of the attacked
      phosphoryl group by sulfur [Stivers, J. T., Shuman, S., & Mildvan, A. S. (1994)
      Biochemistry 33, 327], and the absence of such an effect on kr, (krphos/krthio =
      0.9 +/- 0.2), indicating the rates of cleavage and religation to be limited by
      covalent chemistry and a conformational step, respectively. The rate constant of
      this conformational change in the direction of religation agrees with the average
      rate constant for supercoil release from plasmid substrates, suggesting this
      conformational change to be a part of the topoisomerization step. Although the
      general acid and general base catalysts have not yet been identified, the
      quantitative roles of these and other residues in catalysis are discussed.

PMID- 7803410
TI  - Crystal structure of thymidylate synthase from T4 phage: component of a
      deoxynucleoside triphosphate-synthesizing complex.
AB  - Thymidylate synthase from phage T4 (T4TS) is part of a complex of several enzymes
      required for coordinate DNA synthesis in infected Escherichia coli cells. It has
      been proposed that similar complexes of enzymes related to DNA synthesis are also
      functional in eukaryotes [Pardee, A. B. (1989) Science 246, 603-608]. To
      delineate the role of structure in the function of this complex, we have solved
      the structure of T4TS as a basis for mapping the complex by mutagenesis. The 3.1
      A structure of the unliganded enzyme was determined by molecular replacement and
      refined to 19.9% for all data. Three inserts and one deletion in the coding
      region are unique to T4TS, and all sites lie on one side of the enzyme surface,
      possibly encoding unique T4 specific intermolecular interactions during the
      infective cycle. The crystal structure is generally in the open, unliganded
      conformation seen in unliganded E. coli TS, as opposed to the closed, ternary
      complex conformation, except that the critically important C-terminus is inserted
      into the active site hydrogen bonded to residue Asn85, as seen in functional
      ternary complex structures. Other differences between E. coli TS and T4TS appear
      to explain the enhanced binding of folyl polyglutamate to the latter.

PMID- 7803411
TI  - Active-site mutations of diphtheria toxin: role of tyrosine-65 in NAD binding and
      ADP-ribosylation.
AB  - Previous studies have suggested that tyrosine-65 (Tyr-65) of diphtheria toxin
      (DT) is located at the active site. To investigate the role of Tyr-65 in NAD
      binding and the ADP-ribosylation of elongation factor-2 (EF-2), we changed this
      residue to alanine and phenylalanine by site-directed mutagenesis of a synthetic
      gene encoding the catalytic fragment of DT (DTA). The alanine mutant was greatly
      diminished in ADP-ribosylation activity (350-fold) and NAD-glycohydrolase
      activity (88-fold), whereas the phenylalanine mutant was reduced in these
      activities only slightly. Dissociation constants (Kd) for NAD binding were 15
      microM for wild-type DTA, 26 microM for the phenylalanine mutant, and greater
      than 800 microM NAD for the alanine mutant. However, both mutant enzymes were
      found to bind adenosine with nearly equal affinity as wild-type DTA. These
      results support a model of ADP-ribosylation in which the phenolic ring of Tyr-65
      interacts with the nicotinamide ring of NAD, orienting the N-glycosidic bond of
      NAD for attack by the incoming nucleophile in a direct displacement mechanism.

PMID- 7803412
TI  - Effect of chain length on the formation and stability of synthetic alpha-helical
      coiled coils.
AB  - A series of polypeptides containing 9, 12, 16, 19, 23, 26, 30, 33, and 35 amino
      acid residues was designed to investigate the effects of peptide chain length on
      the formation and stability of two-stranded alpha-helical dimers or coiled coils.
      These peptides were synthesized by the solid-phase method, purified by reversed
      phase high-performance liquid chromatography (RP-HPLC), and characterized by RP
      HPLC, amino acid composition analysis, and mass spectrometry. The amphipathic
      alpha-helical peptides were designed to dimerize by interchain hydrophobic
      interactions at positions a and d and interchain salt bridges between lysine and
      glutamic acid residues at positions e and g of the repeating heptad sequence of
      Glu-Ile-Glu-Ala-Leu-Lys-Ala (g-a-b-c-d-e-f). The ability of these peptides to
      form alpha-helical structures in the presence and absence of a helix-inducing
      reagent (trifluoroethanol) was monitored by circular dichroism spectroscopy. The
      helicity of the peptides increased with increasing chain length in a cooperative
      manner. A minimum of three heptads corresponding to six helical turns was
      required for a peptide to adopt the two-stranded alpha-helical coiled coil
      conformation in aqueous medium. The increased stability of the peptides as a
      result of an increase in hydrophobic interactions (chain length) was demonstrated
      by the shift in the transitions of the guanidine hydrochloride (Gdn.HCl)
      denaturation and thermal unfolding profiles. The concentrations of denaturant
      (Gdn.HCl) required to achieve 50% denaturation are 3.2, 4.9, 6.9, and 7.5 M for
      peptides 23r, 26r, 30r, and 33r, respectively, in aqueous medium. However, the
      effect of a chain length increase on coiled-coil stability was not additive. The
      melting temperature, Tm, at which 50% of the helicity is lost, increased by 34
      degrees C in changing the peptide chain length from 23 to 26; however, that shift
      was only 14 degrees C when the chain length was increased from 30 to 33 residues.
      These results are consistent with a chain length dependent cooperative folding of
      the peptides into coiled coils.

PMID- 7803413
TI  - When does the lung die? I. Histochemical evidence of pulmonary viability after
      "death".
AB  - An inadequate number of lung donors for transplantation results in the death of
      many potential lung recipients awaiting a transplant. Canine experiments in our
      laboratory have shown effective gas exchange in lungs transplanted from cadaver
      donors (lungs retrieved after circulatory arrest). The time course of pulmonary
      cell death after circulatory arrest is unknown. To address this question, we used
      trypan blue dye exclusion to quantitate lung cell death at postmortem intervals
      in rats. One hundred ninety Sprague-Dawley rats were killed and separated into
      four groups: (1) control (n = 10); (2) nonventilated group (n = 60); (3) oxygen
      ventilated group (n = 80); and (4) nitrogen-ventilated group (n = 40). At
      intervals after the animals' deaths, trypan blue was infused into the pulmonary
      artery followed by fixative, and the left lung was excised. Histologic sections
      were prepared for each rat lung, and the percentage of nonviable cells was
      quantified with light microscopy. Control lungs retrieved immediately after death
      showed little or no uptake of trypan blue dye. In nonventilated rats, 36%, 52%,
      and 77% of cells were nonviable in lungs retrieved 2, 4, and 12 hours after
      death, respectively. These results were similar to 34%, 58%, and 71% nonviability
      at the same intervals in nitrogen-ventilated cadaver rat lungs. Oxygen-ventilated
      cadaver rats, however, had significantly fewer nonviable lung cells at each time
      interval: 13%, 10%, and 26%, respectively (p < 0.01). Thus, postmortem mechanical
      ventilation with oxygen appears to delay lung death in the rat after circulatory
      arrest. Nonventilated and nitrogen-ventilated cadaver lungs had a similar
      severity and progression of ischemic injury.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7803414
TI  - When does the lung die? II. Ultrastructural evidence of pulmonary viability after
      "death".
AB  - Lung transplantation as a therapy for end-stage lung disease is limited by the
      paucity of suitable donors. If lungs could be retrieved from circulation-arrested
      cadavers (that is, after death), then more donors for lung transplantation might
      be available. This study was undertaken to determine the time course of
      ultrastructural deterioration of cellular organelles in pulmonary tissue after
      circulatory arrest and death and to determine the effect, if any, of postmortem
      ventilation on the development of these ultrastructural changes. Sprague-Dawley
      rats were sacrificed and then separated into three groups: (1) controls, from
      which the right lung was immediately harvested (n = 4); (2) ventilated group, in
      which mechanical ventilation with 100% oxygen was started after death (n = 15);
      and (3) nonventilated group (n = 15). In the ventilated and nonventilated groups,
      the right lung was harvested at 2, 4, or 8 hours after death. Portions of the
      lung from each rat were examined by electron microscopy, and each specimen was
      assigned a semiquantitative injury score that was based on nuclear chromatin
      clumping, mitochondrial degeneration, intracellular edema, and cellular membrane
      integrity. The lung in all four controls was normal. At 4 and 8 hours postmortem,
      ultrastructural damage was significantly attenuated in rats with oxygen
      ventilation compared with those in the nonventilated group. The degree of
      ultrastructural damage observed in the oxygen ventilation group at 2 and 4 hours
      postmortem was not significantly different from that of normal controls. Thus,
      mechanical ventilation with oxygen after death appears to preserve lung
      ultrastructure and may delay cell death. This study supports the hypothesis that
      lung transplantation from cadaver donors may be feasible.

PMID- 7803415
TI  - Causes of death in lung transplant recipients.
AB  - Between November 1983 and September 1992, The Toronto Lung Transplant Program
      performed 131 lung transplantations in 122 recipients; 53 single lung
      transplantations and 78 double lung transplantations. Forty-five patients died,
      25 (47%) in the single lung transplantation and 20 (25%) in the double lung
      transplantation groups. We retrospectively reviewed the hospital charts of all
      deceased recipients and the postmortem reports of the 35 patients (20 single lung
      transplantations and 15 double lung transplantations) who had autopsies.
      Preoperative single lung transplantation diagnoses included pulmonary fibrosis,
      (n = 17) obstructive disease (n = 6) and vascular disease (n = 2). Preoperative
      diagnosis of double lung transplantation included pulmonary fibrosis (n = 2),
      obstructive disease (n = 6), septic lung disease (n = 9), and vascular disease (n
      = 3). The most common cause of death in single lung transplantation was
      infection. Five patients died of bronchiolitis obliterans, and five more had
      bronchiolitis obliterans lesions present at autopsy that were not a direct cause
      of death. Diagnosis of primary disease was made in 23 of 25 single lung
      transplantations antemortem and 2 of 25 at autopsy. Autopsy diagnoses were
      disseminated Aspergillus and cytomegalovirus infection. In double lung
      transplantations, infection was also the primary cause of death; in three other
      patients, airway dehiscence preceded infection. Bronchiolitis obliterans was the
      second most common cause of death and was also present in four patients dying of
      infection. All double lung transplantation diagnoses were made antemortem. We
      concluded that infection and then bronchiolitis obliterans are the primary causes
      of death after lung transplantation. Although infection is a major cause both
      early and late after transplantation, bronchiolitis obliterans is an important
      factor in transplantation only late after the operation.

PMID- 7803416
TI  - Wrapping the anastomosis with omentum or an internal mammary artery pedicle does
      not improve bronchial healing after single lung transplantation: results of a
      randomized clinical trial.
AB  - Between May 1989 and March 1990, 36 patients undergoing a first single lung
      transplantation were randomized to three groups. In the omentum group the
      bronchial anastomosis was wrapped with an omental pedicle. In the internal
      mammary artery group, the anastomosis was wrapped in a pedicle of tissue
      surrounding the internal mammary artery. In the no wrap group, no attempt was
      made to revascularize the anastomosis. No significant differences were found in
      the indications for transplantation, recipient age, organ ischemic time, or
      preoperative steroid use in the three groups. There were two early deaths: one in
      the omentum group as a result of infection and one in the internal mammary artery
      group as a result of multiorgan failure. During a mean follow-up period of 21
      months (range 9 to 32), there were two additional deaths in the no wrap group and
      four in the omentum group, one of which involved an anastomotic complication.
      Actuarial survival at 1 year was 75%, 92%, and 80% in the omentum, internal
      mammary artery, and no wrap groups, respectively (p = 0.25). Granulation tissue
      at the site of the anastomosis requiring cryotherapy or bronchial dilatation
      occurred in two patients in the omentum group, three in the internal mammary
      artery group, and three in the no wrap group. Bronchial stents were required in
      one patient in the omentum group and one in the internal mammary artery group.
      Actuarial survival free of anastomotic complications was similar in the three
      groups. The incidence of bronchial anastomotic complications after single lung
      transplantation is not affected by wrapping the anastomosis with either omentum
      or an internal mammary artery pedicle.

PMID- 7803418
TI  - Slow-rate, high-pressure ventilation: a method of management of difficult
      transplant recipients during sequential double lung transplantation for cystic
      fibrosis.
AB  - Single and double lung ventilation can be extremely difficult in patients with
      cystic fibrosis who require sequential double lung transplantation. This article
      reports the successful use of slow-rate, high-pressure ventilation in the
      management of two ventilator-dependent patients who would otherwise have needed
      to be supported by cardiopulmonary bypass.

PMID- 7803417
TI  - Airway stenoses after lung transplantation: management with expanding metal
      stents.
AB  - Success in lung transplantation has been hindered by airway complications,
      usually as a result of anastomotic ischemia and stenosis. We report our
      experience with expanding metal stents in managing airway stenoses after lung
      transplantation. From April 1984 through November 1993, 46 single lung, 5 double
      lung, and 154 heart-lung transplantations were performed at Papworth Hospital.
      All patients received immunosuppression with azathioprine, cyclosporine,
      methylprednisolone, and induction antithymocyte globulin. Fourteen patients (nine
      single lung, two double lung, and three heart-lung) had an airway stenosis
      requiring a stent. The most common features were shortness of breath, wheezing or
      stridor, and a fall in pulmonary function tests (11 patients). Three patients had
      pneumonia. Airway stenosis was diagnosed on bronchoscopy an average of 61 days
      after transplantation (range 3 to 245 days). Stent placement occurred an average
      of 18 days after the diagnosis (range 2 to 84 days). One heart-lung transplant
      recipient received a silicone rubber stent. All other patients received expanding
      metal stents. Six patients required multiple stent placements. After stent
      placement the average increase in the forced expiratory volume in 1 second was
      117%. Infection complicated the stenoses in 12 patients. Pseudomonas aeruginosa
      and Aspergillus fumigatus were the most common pathogens, each occurring in six
      cases. Multiple pathogens were isolated in seven cases. Three patients died as a
      direct consequence of their airway problems. Two died of pneumonia despite
      stenting, and a third died of acute occlusion of the silicone rubber stent.
      Expanding metal stents are an effective treatment of airway stenoses in lung
      transplant recipients. Patients with suspected airway problems should be referred
      for early bronchoscopy with the potential for stent placement.

PMID- 7803419
TI  - Fatal fat embolism syndrome after numerous vertebral body compression fractures
      in a lung transplant recipient.
AB  - The fat embolism syndrome is an uncommon clinical disorder that typically occurs
      as a complication of severe trauma. We report the case of a 60-year-old single
      lung transplant recipient who died of massive fat emboli. Before lung
      transplantation, the patient had been treated with corticosteroids for at least 1
      year because of chronic obstructive pulmonary disease caused by centrilobular
      emphysema and asthmatic bronchitis. After receiving his lung transplant, he was
      treated with triple-drug immunosuppression, which included 25 mg of prednisone
      per day. He was discharged from the hospital 2 months after transplantation only
      to be readmitted 2 weeks later with cytomegalovirus pneumonia, from which he
      recovered. Concomitantly, he had new lumbar compression fractures with severe
      back pain and lost approximately 3 cm in height during a 3-week period. On the
      eleventh day after hospital readmission, he suddenly had a "sepsis-like" illness
      without a known infectious cause, numerous petechiae and ecchymoses, marked
      pulmonary edema with worsening diffuse pulmonary infiltrates, profound hypoxemia,
      decreased mentation, and mild thrombocytopenia. He died 3 days later. With the
      exception of a positive sputum culture for cytomegalovirus, all cultures were
      negative. The postmortem examination showed severe osteoporosis, multiple
      vertebral compression fractures, and widespread massive fat emboli. This is the
      first reported case of fat emboli as the cause of death in a lung transplant
      recipient, and the case suggests that the fat embolism syndrome should be
      considered in the differential diagnosis of a sepsis-like illness in patients who
      have received steroids during a long period, particularly in the setting of
      vertebral compression fractures.

PMID- 7803420
TI  - The function of surfactant is impaired during the reimplantation response in rat
      lung transplants.
AB  - In this study we investigated the surfactant function in rat lung transplants at
      the peak of the reimplantation response in experimental groups with increasing
      warm ischemic times of the lung transplant. The left and right lungs in five
      groups of rats were assessed 24 hours after left lung transplantation: rats
      receiving transplants with lung graft ischemic times of 60 (n = 4), 90 (n = 5),
      and 120 (n = 5) minutes, donor rats with 120 minutes lung ischemia (n = 5) and
      normal (nonoperated) rats (n = 6). The reimplantation response was assessed by
      the ventilation score on chest roentgenograms, measurement of the static lung
      compliance, and the (serum) protein concentration in the bronchoalveolar lavage
      fluid. Surfactant in the bronchoalveolar lavage fluid was assessed by measuring
      the amount and the composition of surfactant phospholipids and the in vitro
      surfactant function in a pulsating bubble surfactometer. We found that longer
      ischemic times caused a more severe reimplantation response in the left lung
      grafts. Although the ventilation scores were equally low in the 60-, 90-, and 120
      minute ischemia groups, the lung compliances decreased and the (serum) protein
      concentrations increased stepwise in correlation with longer ischemic times. The
      amount of surfactant phospholipids during the reimplantation response was not
      changed, but the percentage phosphatidyl choline decreased progressively in
      parallel with the severity of the reimplantation response. Finally, the in vitro
      function of surfactant from the lung transplants decreased in parallel with the
      prolongation of the ischemic time, whereas the function of surfactant from donor
      lungs with 120 minutes of ischemia and from native right lungs was not changed.
      We conclude that the surfactant function is impaired during the reimplantation
      response as a result of a high concentration of inhibiting serum proteins and a
      low percentage of phosphatidyl choline.

PMID- 7803421
TI  - Eleven years' experience with the Pierce-Donachy ventricular assist device.
AB  - During the last decade, mechanical circulatory support has been used in patients
      with cardiogenic shock refractory to conventional therapy. Since 1982, we
      supported 77 patients (78 implants) with Pierce-Donachy external pneumatic
      ventricular assist devices. Forty-two patients (35 after cardiotomy, four after
      heart transplantation, and three with acute infarction) 15 to 71 years of age
      (mean age 52 years) were supported for cardiac recovery. Left ventricular assist
      devices were used in 16 patients, right ventricular assist devices plus
      intraaortic balloon were used in nine, and biventricular assist devices were used
      in 17. Patients were supported 0.2 to 17 days (mean 4.4 days), 18 patients (43%)
      were weaned, and 11 (26%) survived. Complications included acute myocardial
      infarction (60%), bleeding (48%), infection (38%), and renal failure (24%).
      Bridging to transplantation was attempted in 35 patients (one patient underwent
      the procedure twice), 12 to 63 years of age (mean age 40 years). Left ventricular
      assist devices were used 19 times, and biventricular assist devices were used 17
      times. Duration of support was 0.2 to 95 days (mean 24 days). All 20 patients who
      underwent transplantation were discharged. Of the 15 patients who did not undergo
      transplantation, two were weaned and survived, whereas the remaining 13 patients
      (who did not undergo transplantation because of complications) died with the
      device in place. In the patients in the bridge to transplantation group, bleeding
      occurred in 26%, infection in 55%, and renal failure in 15%. In the entire group
      of 77 patients, the incidence of ventricular assist device-related
      thromboembolism was 6%, but only 4% had neurologic deficits.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7803422
TI  - Narrowing the organ donation gap: hospital development methods that maximize
      hospital donation potential.
AB  - The purpose of this article is to identify and describe this organ procurement
      organization's hospital development methods that have markedly increased the
      quantity and quality of organ donor referrals. Procedures used include the
      establishment of organ donor programs (hospital donor programs) within each donor
      hospital. The goal for these hospital donor programs is to monitor and maximize
      organ procurement within each institution. Routine quality assurance or death
      audits along with referral data from the organ procurement organization's
      database provide both the organ procurement organization and the hospital donor
      program with the necessary information to evaluate organ procurement strengths
      and weaknesses. This data is used in concert with ongoing development activities,
      which include, but are not limited to, physician and staff education and frequent
      marketing visits. Early referral to the organ procurement organization of all
      nonsurvivable head injuries for evaluation as potential organ donors, and a
      timely request for donation by the organ procurement organization coordinator are
      emphasized. The results of these efforts have been gratifying. In 1989, 138
      referrals and 41 organ donations occurred. In 1990, 174 referrals and 66 organ
      donations occurred. In 1991, 213 referrals and 71 organ donations occurred. In
      1992, 228 referrals and 70 organ donations occurred. In the first 6 months of
      1993, 146 referrals and 40 organ donations occurred, for a prorated figure of 292
      referrals and 80 organ donations annually. In conclusion, these results appear to
      validate the benefits of this approach and its significant contribution to
      narrowing the donation supply and demand gap.

PMID- 7803423
TI  - Comparable proximal and distal severity of intimal thickening and size of
      epicardial coronary arteries in transplant arteriopathy of human cardiac
      allografts.
AB  - Previous angiographic observations have characterized transplant atherosclerosis
      as a generally diffuse and more distally severe disease with obliteration of
      secondary branches. However, it has not been firmly established that the disease
      is structurally and biologically more severe distally. We evaluated this
      hypothesis with computer-based digitization of subserial segments of the entire
      perfusion-fixed left anterior descending coronary artery (100 mm Hg for 1 hour
      with 10% formaldehyde solution) in 25 allografts at autopsy or explant (19 male
      and 6 female patients; mean age = 50 years, range 16 to 66; mean implant duration
      = 490 days, range 3 to 1610). The area, thickness, circumference of the intima
      and media, and the relative and absolute luminal narrowing were evaluated in a
      mean of 10 left anterior descending coronary artery sections per allograft. The
      percentage of luminal narrowing (intimal area/[intimal area + luminal area] x
      100) was similar between proximal and distal segments of the left anterior
      descending coronary artery (45% versus 41%, p > 0.05), and the mean absolute
      intimal thicknesses (in millimeters) of proximal and distal segments of the left
      anterior descending coronary artery also were not different (0.32 versus 0.22, p
      > 0.05). In addition, the 95% confidence intervals for intimal thicknesses of
      proximal and distal segments were comparable. Because the absolute arterial size
      of proximal segments is naturally larger than that of distal segments (external
      diameter 9.37 versus 6.79, p < 0.0001), an appearance of progressive tapering may
      be visualized angiographically, even though the biologic severity of the disease
      is geographically uniform. Similarly, observations of obliterated secondary
      branches in distal segments may result from naturally smaller distal luminal
      areas which may be occluded by less intimal thickening than would be required
      proximally. These data emphasize that transplant atherosclerosis is biologically
      uniform from proximal to distal locations. Etiologic and pathogenetic studies on
      proximal or distal segments should be equally informative.

PMID- 7803424
TI  - Methylergonovine-induced diffuse coronary spasm in a patient with exercise
      induced coronary spasm after heart transplantation.
AB  - Coronary artery spasm is a rarely reported condition after heart transplantation.
      We report a case of exercise-induced coronary artery spasm in a patient 1-year
      after orthotopic heart transplantation. Serial quantitative coronary angiography
      showed significant diffuse loss of luminal diameter. Provocative testing with
      intracoronary acetylcholine and intravenous methylergonovine maleate was
      performed in an effort to document efficacy of the antispasm regimen. Infusion of
      acetylcholine into the left anterior descending coronary artery resulted in
      transient closure of the vessel. Diffuse spasm resulting in hypotension and
      ventricular fibrillation occurred with intravenous methylergonovine maleate
      administration. Because of the risk of provoking diffuse spasm, intravenous
      administration of methylergonovine maleate should be avoided in the
      posttransplantation setting. Review of the literature suggests that coronary
      artery spasm after transplantation is often associated with severe transplant
      coronary artery disease and may be associated with a poor prognosis. Coronary
      artery spasm may be a more common cause of syncope and death after
      transplantation than it is currently thought to be.

PMID- 7803425
TI  - Physiologic assessment of the coronary collateral circulation in transplanted
      human hearts.
AB  - Coronary arteries of transplanted hearts frequently develop a vasculopathy
      characterized by severe lumenal narrowing in the distal coronary arteries. It has
      been thought, on the basis of angiographic studies, that the coronary circulation
      of transplanted hearts with vasculopathy fails to develop collateral vessels
      normally. To determine the extent of the collateral circulation in transplanted
      hearts with a significant coronary stenosis, we measured an index of the
      collateral circulation, the coronary artery occlusion pressure, during single
      vessel coronary angioplasty in seven patients with allograft vasculopathy and 18
      patients with atherosclerotic disease who did not undergo transplantation. Aortic
      and coronary artery pressure distal to the stenosis in the epicardial artery were
      measured during balloon occlusion (> or = 45 seconds). Measurement variability
      for determination of coronary occlusion pressure was assessed by measuring
      occlusion pressure on two separate balloon inflations (n = 17). The severity of
      the dilated stenotic lesion was assessed with quantitative angiography (Reiber
      PIE Data method). The indexes of stenosis severity were similar in coronary
      arteries of transplanted and native hearts. Coronary occlusion pressure
      measurements were highly reproducible (mean absolute difference between
      measurements, 1 +/- 1 mm Hg, r = 0.98). Coronary occlusion pressure in
      transplanted hearts (32 +/- 4 mm Hg) was nearly identical to that measured in
      coronary arteries of native hearts (29 +/- 2 mm Hg). When vessels with total
      occlusion were excluded and corrections were made for minor differences in
      hemodynamics (heart rate and blood pressure) were made, the coronary occlusion
      pressure in transplanted hearts remained nearly identical to native
      hearts.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7803426
TI  - Capacity of intrinsic cardiac neurons to modify the acutely autotransplanted
      mammalian heart.
AB  - The capacity of the intrinsic cardiac nervous system to modify the acutely
      autotransplanted heart was investigated in eight anesthetized open-chest canine
      preparations in which the adrenal glands had been removed from the circulation.
      Cardiac effects elicited by isoproterenol and nicotine were also examined before
      and after heart-lung transplantation. Cardiac augmentation induced by
      isoproterenol was similar before and immediately after cardiopulmonary
      transplantation, indicating that the surgery did not obtund cardiac myocyte
      function significantly. The initial bradycardia induced by nicotine was greater
      before transplantation. The subsequent augmentation in left atrial systolic
      pressure, as well as right and left ventricular intramyocardial systolic
      pressures, induced by nicotine were similar before and after transplantation.
      When nicotine was administered to transplanted preparations after atropine
      administration, cardiac augmentation was induced. Cardiac augmentation was not
      induced by nicotine after subsequent beta-adrenergic blockade. These data
      indicate that nicotine-sensitive adrenergic neurons which accompany the
      transplanted heart are capable of inducing considerable cardiac augmentation.
      Power spectral analysis of heart rate and left ventricular chamber rate of
      pressure rise variability indicated an almost complete lack of power in these
      indexes after, as opposed to before, transplantation. Together with intrinsic
      cardiac cholinergic neurons, intrinsic cardiac adrenergic neurons may be
      responsible for physiologically and pharmacologically induced alterations in
      cardiac variables that occur in acutely transplanted hearts.

PMID- 7803427
TI  - Myocardial high-energy phosphate depletion in allograft rejection after
      orthotopic human heart transplantation.
AB  - The present study was designed to assess whether acute rejection affects
      myocardial energy content of the human orthotopically transplanted heart.
      Adenosine triphosphate content was measured in one tissue sample obtained during
      46 routine right ventricular endomyocardial biopsies 6 to 455 days (98 +/- 110)
      after transplantation in 19 cyclosporine-treated transplant recipients. Tissue
      samples were immediately frozen in liquid nitrogen within 10 seconds after
      excision. Adenosine triphosphate analysis was performed with high performance
      liquid chromatography. Three groups of biopsy specimens were classified according
      to the standardized cardiac biopsy grading system. Group 1: Eight biopsy
      specimens without rejection; group 2: 24 biopsy specimens with mild rejection;
      group 3: 14 biopsy specimens with moderate or severe rejection. Graft systolic
      function evaluated by echocardiographic fractional shortening was in the normal
      range the day of biopsy. All patients had normal coronary angiograms within 1
      month of the study. In the presence of mild rejection (grade 1A or 1B), adenosine
      triphosphate content was not significantly different from that of nonrejecting
      hearts (26.15 +/- 7.1 and 28.57 +/- 8.23 nmol/mg protein, respectively). By
      contrast, a significant decrease in adenosine triphosphate content was observed
      when moderate or severe rejection with focal or diffuse aggressive infiltrates
      were present (10.46 +/- 4.11 nmol/mg protein; p < 0.01 versus two other groups).
      In seven cases, sequential analysis showed a significant increase in adenosine
      triphosphate content after rejection therapy concomittant with histologic
      improvement: 10.19 +/- 2.9 before and 30.13 +/- 7.0 nmol/mg protein after
      treatment (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7803428
TI  - Acute rejection: significance of elapsed time after transplantation.
AB  - In July 1990 the new standardized grading scheme for the International Society
      for Heart and Lung Transplantation was established. One of the purposes of
      "splitting" the grades was to learn the significance and outcome of the various
      grades proposed. Between January 1990 and November 1992, 263 grade 1A, 19 grade
      1B, and 100 grade 2 "new" rejection episodes were identified at our institution.
      These episodes occurred in 86 adult recipients who underwent transplantation
      between January 1990 and August 1992 and 98 recipients who underwent
      transplantation before January 1990, in whom the episodes occurred more than 1
      year from the date of transplantation. The outcome of the episode was determined
      on subsequent endomyocardial biopsy samples to be resolution or "progression" to
      a higher grade. The percentage of focal mild (grade 1A) rejection episodes
      progressing to a moderate (grade 3A) rejection in the first 6 months after
      transplantation was 24.4% (20 of 82) compared with a progression rate of 5.1% (3
      of 59) and 2% (3 of 149) in episodes occurring beyond 6 months and 1 year after
      transplantation, respectively (p < 0.005). Of the focal moderate (grade 2)
      rejection episodes receiving no augmentation of immunosuppression, 35.7% (5 of
      14) occurring within the initial 6 months and 7.3% (3 of 41) of all such episodes
      diagnosed beyond 1 year after transplantation progressed to a moderate rejection.
      A similar trend was seen in the focal moderate rejection episodes that received
      augmentation of immunosuppression: 26.3% (5 of 19) of episodes occurring within 6
      months and 0 of 15 of all episodes occurring beyond 1 year after transplantation
      progressed to a moderate rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7803430
TI  - Cytoimmunologic monitoring after heart transplantation.

PMID- 7803429
TI  - Cytoimmunologic monitoring as an adjunct in monitoring rejection after heart
      transplantation: results of a 6-year follow-up in heart transplant recipients.
AB  - The cytoimmunologic monitoring assay has been proposed as a useful noninvasive
      technique in the diagnosis of rejection and infection after heart
      transplantation. In this study, we have analyzed the diagnostic usefulness of
      cytoimmunologic monitoring in 73 patients after heart transplantation. For
      individual patients, the follow-up varied between 2 and 78 months. Data were
      related to histopathologic characteristics of the endomyocardial biopsy.
      Significantly different cytoimmunologic monitoring results were not observed
      between groups according to endomyocardial biopsy histopathologic evaluation. The
      diagnostic usefulness of cytoimmunologic monitoring depended on the cutoff value
      applied. With higher cutoff values, the sensitivity decreased and the specificity
      and predictive value increased. For the previously reported cutoff value of 5%,
      the sensitivity was 0.29, the specificity was 0.73, and the predictive value was
      0.66. Values of sensitivity, specificity, and predictive value were similar when
      only the first acute rejection was taken into account, or when only data on the
      first 4 weeks and the first 6 months after transplantation were considered. In
      calculating the diagnostic usefulness of the sensitivity, specificity, and
      predictive values were observed. We concluded that cytoimmunologic monitoring has
      a limited value for diagnosing acute rejection after heart transplantation.

PMID- 7803431
TI  - Human plasma causes rapid dysfunction in ex vivo pig hearts.
AB  - The use of hearts from large domestic animals represents a potential solution to
      the current human donor shortage. However, xenogeneic hyperacute graft rejection
      remains a major barrier to xenotransplantation. The purpose of this study was to
      use an ex vivo preparation to study variables that may correlate with hyperacute
      rejection in cardiac xenografts. Freshly excised hearts from 37 anesthetized pigs
      (10 to 37 kg) were perfused at 37 degrees C through the aorta with retrograde
      flow. The hearts functioned in a nonworking mode for 4 hours or until
      irreversible cardiac dysfunction occurred. Various perfusates were used: fresh
      whole autologous pig blood (n = 4), dog blood (n = 3), baboon blood (n = 5),
      human packed red blood cells (n = 2), human whole blood (n = 10), human whole
      blood and plasma (n = 3), and human plasma (n = 9), to which a modified Krebs
      Henseleit bicarbonate buffer solution was added. Rapid loss of function was
      uniform and occurred most quickly (13 to 18 minutes) for hearts perfused with dog
      blood and human plasma. Isolated cardiac perfusion provided a means for the
      analysis of the cellular and plasma components of human blood to define which
      were required for rapid loss of function. The results indicated that the reaction
      was mediated by components present only in plasma.

PMID- 7803432
TI  - Twenty-four hour intermittent perfusion storage of the isolated rat heart: the
      effect of perfusion intervals on functional preservation.
AB  - We investigated the effect of intermittent perfusion intervals on heart
      preservation. The isolated rat heart was flushed with a cardioplegic solution, CP
      11EB, and stored at 0 degrees C for 24 hours. During storage, the heart was
      perfused periodically at 60 mm Hg for 3 minutes with 25 degrees C oxygenated CP
      11EB. The perfusion schedules were as follows: group I, every 4 hours; group II,
      every 6 hours; group III, every 8 hours; group IV, every 10 hours; group V, 10
      and 17 hours of storage; group VI, every 11 hours. Poststorage function was
      assessed after 30 minutes of working reperfusion. Function of the unstored hearts
      including aortic flow (51.5 +/- 2.5 ml/min), coronary flow (24.5 +/- 1.3 ml/min),
      cardiac output (75.6 +/- 3.0 ml/min) and work (85.0 +/- 5.4 g-ml/min) served as
      controls. Group V hearts were best preserved with aortic flow recovered to 65%;
      coronary flow 44%; cardiac output 58%; and work 53% of the control. Recovery in
      group IV was comparable with group V. Groups I, II, III, and VI recovered
      significantly less than group V. Myocardial adenosine triphosphate content
      (micromoles per gram dry) in group V was 23.8 +/- 1.7, 20.8 +/- 0.9, 13.5 +/-
      2.4, and 15.0 +/- 4.0, at 0, 10, 17, and 24 hours of storage, respectively.
      Intermittent perfusion at 10 and 17 hours elevated adenosine triphosphate to 99%
      and 88% of prestorage level. Poststorage reperfusion did not improve improve
      adenosine triphosphate content (16.2 +/- 2.4) over the end-storage
      level.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7803433
TI  - Effects of cyclosporine and 15-deoxyspergualin on coronary arteriosclerosis after
      heart transplantation in the rat.
AB  - The development of graft coronary arteriosclerosis remains a serious consequence
      after heart transplantation and may limit long-term survival. The purpose of this
      study was to evaluate the effects of 15-Deoxyspergualin on graft coronary
      arteriosclerosis after heterotopic heart transplantation in a rat model and
      compare the effects to those of cyclosporine treatment. Two groups of Lewis rats
      (n = 7 each group) underwent heterotopic heart transplantation from Fischer 344
      donors and were treated with either cyclosporine (10 mg/kg/day) or 15
      Deoxyspergualin (3 mg/kg/day). Histologic evaluations of rejection (scale: 0 =
      none, 3 = severe) and graft coronary arteriosclerosis (scale: 0 = normal, 4 =
      occluded) were made 60 days after transplantation. No significant difference was
      found between the two groups with respect to the degree of rejection (2.0 +/- 0.7
      in the cyclosporine-treated group versus 2.0 +/- 0.5 in the 15-Deoxyspergualin
      treated group). However, the extent of graft coronary arteriosclerosis in the 15
      Deoxyspergualin-treated group was significantly less than that seen in the
      cyclosporine-treated group (1.11 +/- 0.34 versus 1.71 +/- 0.24, p < 0.01).
      Furthermore, the incidence of diseased vessels among all observed vessels was
      significantly lower in the 15-Deoxyspergualin-treated group compared with the
      cyclosporine-treated group (63% +/- 12% versus 76% +/- 7%, p < 0.05). Although
      the protective mechanism of 15-Deoxyspergualin is unknown, it most likely
      possesses a different immunosuppressive mechanism of action from cyclosporine. We
      concluded that 15-Deoxyspergualin is superior to cyclosporine in preventing graft
      coronary arteriosclerosis after heart transplantation.

PMID- 7803435
TI  - Radiofrequency ablation of Wolff-Parkinson-White syndrome in a donor heart after
      orthotopic heart transplantation.
AB  - Orthotopic heart transplantation was performed in a 65-year-old man with a donor
      heart with Wolff-Parkinson-White Syndrome. An electrophysiologic study performed
      7 days after transplantation showed a left-lateral accessory pathway that
      exhibited only anterograde conduction. Radiofrequency ablation of the bypass
      tract was successfully performed, and no evidence of recurrence was found at 12
      months' follow-up. We suggest that potential donors with known electrophysiologic
      abnormalities that are amenable to catheter ablation techniques should be
      considered for orthotopic heart transplantation, thus broadening the potential
      donor pool.

PMID- 7803434
TI  - Heart transplantation in patients with Marfan's syndrome: a survey of attitudes
      and results.
AB  - Our institution performed an orthotopic heart transplantation in a patient with
      Marfan's syndrome. The immediate postoperative course was complicated with
      ultimate discharge; however, this patient died within 1 year as a result of an
      aortic dissection. On the basis of our experience, we surveyed all heart
      transplant centers listed with the North American Transplant Coordinator
      Organization for other patients with Marfan's syndrome who had been referred for
      transplantation. Nearly one third of responding centers evaluated a total of 30
      patients with Marfan's syndrome. Of these, only 13 were formally listed for a
      donor organ and 11 underwent heart transplantation with an operative mortality of
      9.1% (n = 1). Posttransplantation morbidity was significant and includes a 40% (n
      = 4) incidence of thoracic aorta dissection (one fatal) in operative survivors.
      There were three other non-dissection-related late deaths for an overall survival
      of 54.4% after a mean follow-up of 33.0 months. In this shared experience, it
      appears that the known vascular complications of Marfan's syndrome may diminish
      the anticipated results after heart transplantation. The reluctance to place
      these patients on heart transplant donor waiting lists can be justified.

PMID- 7803436
TI  - Cardiac tamponade masked by bilateral internal jugular vein thrombosis: its
      occurrence in an orthotopic heart transplant recipient.
AB  - We present a case of cardiac tamponade masked by bilateral internal jugular vein
      thrombosis occurring in a patient 1 month after orthotopic heart transplantation.
      Because patients who undergo heart transplantation undergo both heart surgery and
      multiple endomyocardial biopsies, they are at risk for both of these
      complications. Therefore when evaluating hypotensive patients who are at risk for
      both pericardial effusion and bilateral internal jugular vein thrombosis, cardiac
      tamponade should not be excluded, even in the absence of jugular vein distention.

PMID- 7803437
TI  - Visceral Kaposi's sarcoma without mucocutaneous involvement in a heart transplant
      recipient.
AB  - Kaposi's sarcoma has been occasionally reported in heart transplant recipients,
      but its occurrence without mucocutaneous involvement is extremely rare. In these
      uncommon cases, the tumor can be indistinguishable from opportunistic infections,
      making diagnosis difficult. The case of a patient in whom visceral Kaposi's
      sarcoma was diagnosed by necropsy 6 months after heart transplantation is
      reported.

PMID- 7803439
TI  - Successful repair of recurrent coarctation after neonatal heart transplantation.
AB  - Neonatal orthotopic heart transplantation is an attractive primary surgical
      therapy for severe uncorrectable congenital heart defects such as variants of the
      hypoplastic left heart syndrome. Aortic arch reconstruction is frequently
      required to repair the hypoplastic aortic arch and the coarctation at the time of
      graft implantation. Residual coarctation of the aorta after neonatal heart
      transplantation for such a condition has satisfactorily been treated with
      percutaneous balloon dilatation. We describe the successful surgical repair of a
      recurrent coarctation of the aorta via a sternotomy in a 2-year-old patient who
      had previously undergone neonatal orthotopic heart transplantation. Postoperative
      periodic investigations have not shown any evidence of obstruction across the
      site of the primary end-to-end anastomosis.

PMID- 7803438
TI  - Toxoplasmosis after heart transplantation: diagnosis by endomyocardial biopsy.
AB  - Protozoal infections such as toxoplasmosis are known complications in heart
      transplant recipients. Diagnosis of the disease is often difficult. This article
      describes the course of a patient who had a febrile illness with leukocytosis and
      neurologic disorders after heart transplantation; all microbiologic and serologic
      tests of the peripheral blood and the cerebrospinal fluid failed to identify the
      responsible pathogen. Infection with Toxoplasma gondii was finally diagnosed by
      endomyocardial biopsy. We conclude that in heart transplant recipients with
      infections of unclear origin and neurologic disorders, endomyocardial biopsy may
      be helpful in the diagnosis, especially in cases of toxoplasmosis.

PMID- 7803440
TI  - Successful treatment of a cardiac angiosarcoma with combined modality therapy.
AB  - The patient was a 34-year-old man with a primary angiosarcoma of the heart.
      Initial admission was for cardiac tamponade. He was treated with preoperative
      chemotherapy and radiation therapy and then underwent orthotopic heart
      transplantation. The patient had an uneventful postoperative recovery, received
      two postoperative regimens of chemotherapy, and, at 33 months after
      transplantation, had no evidence of recurrence or metastasis. We propose that a
      more aggressive management of these patients with difficult conditions is
      warranted.

PMID- 7803441
TI  - Mycotic false aneurysm of the aortic suture line after heart transplantation.
AB  - Aortic suture line infection caused by Pseudomonas aeruginosa occurred in a 31
      year-old man 2 months after orthotopic heart transplantation. Incomplete
      resection of the mycotic aneurysm and replacement of the ascending aorta with
      allograft aorta was performed. Subsequently, the infection recurred on the
      proximal suture line, and reoperation with complete excision of the mycotic
      aneurysm and allograft replacement of the ascending aorta was performed
      successfully, without recurrence of the infection.

PMID- 7803442
TI  - Coronary artery fistula and unstable angina complicating posttransplantation
      surveillance right ventricular endomyocardial biopsy.

PMID- 7803443
TI  - Medication noncompliance and its relationship to financial factors after heart
      transplantation.

PMID- 7803444
TI  - Nickel hydrogenases: in search of the active site.

PMID- 7803446
TI  - Kinetic characterization of the reconstituted ornithine carrier from rat liver
      mitochondria.
AB  - The ornithine carrier was purified from rat liver mitochondria and reconstituted
      into liposomes by removing the detergent from mixed micelles by hydrophobic
      chromatography on Amberlite XAD-2. The efficiency of reconstitution was optimized
      with respect to the concentration of protein and phospholipid, the Triton X
      100/phospholipid ratio, the Amberlite/detergent ratio and the number of passages
      through a single Amberlite column. The activity of the carrier was influenced by
      the phospholipid composition of the liposomes, increasing in the presence of
      acidic phospholipids and decreasing in the presence of
      dioleoylphosphatidylcholine. In the reconstituted system the incorporated
      ornithine carrier catalyzed a first-order reaction of ornithine/ornithine or
      ornithine/citrulline exchange. The maximum transport rate of external
      [14C]ornithine was 3.2 mmol/min per g protein at 25 degrees C. This value was
      independent of the type of substrate present at the external or internal space of
      the liposomes (ornithine, citrulline and lysine). The half-saturation constant
      (Km) was 0.16 mM for ornithine, 1.2 mM for lysine and 3.6 mM for citrulline. The
      activation energy of the ornithine/ornithine exchange reaction was 89 kJ/mol. The
      rate of exchange had a pH optimum at 8 and was inhibited by cations.

PMID- 7803447
TI  - Over-expression of membrane-bound cytochrome c-551 from thermophilic Bacillus PS3
      in Bacillus stearothermophilus K1041.
AB  - Cytochrome c-551 is a lipoprotein of about 10500 Da, found in thermophilic
      Bacillus PS3 grown under air-limited conditions. An expression vector was
      constructed from a structural gene of PS3 cytochrome c-551, synthetic
      oligonucleotide as a promoter for Bacillus stearothermophilus and a shuttle
      vector for Escherichia coli and B. stearothermophilus. The transformed cells of
      B. stearothermophilus K1041 expressed cytochrome c-551 as much as 5 nmol/mg
      membrane protein. The effects of over-expression on the host cells are analyzed;
      a slightly slower growth rate and an increased synthesis of cytochrome oxidase
      (about twofold) occurred. Over-expressed (4-10-fold) cytochrome c-551 were
      purified and its properties were examined to know whether the protein is
      processed as in PS3 cells grown under air-limited conditions. The molecular mass
      determination and treatment with Rhizopus lipase suggested that the same
      processes, cleavage of signal peptidase, blocking of the N-terminal group and
      acylation of glycerol residue by two fatty acids, took place in the over
      expression system. Fatty acylation seems useful for the cytochrome c to be
      effectively oxidized.

PMID- 7803445
TI  - The light-driven proton pump, cruxrhodopsin-2 in Haloarcula sp. arg-2 (bR+, hR-),
      and its coupled ATP formation.
AB  - Haloarcula sp. arg-2, a natural bacterial isolate from Andes heights, has a light
      driven proton pump but not a light-driven anion pump. We have cloned and
      sequenced the gene encoding for the proton pump which has been named
      cruxrhodopsin-2. The gene consists of 768 bp encoding 255 amino acids with a
      molecular mass of 27,544 Da. The deduced amino acid sequence of cruxrhodopsin-2
      is 77%, 50%, 48% and 48% identical to those of cruxrhodopsin-1,
      bacteriorhodopsin, archaerhodopsin-1 and archaerhodopsin-2, respectively. The
      charged amino acids important for the proton pump function were conserved among
      all these molecules. Cruxrhodopsin-2 accounted for 0.05 nmol/mg protein in arg-2,
      which was 20-30-fold less than the proportion of bacteriorhodopsin in
      Halobacterium salinarium R1M1. In contrast to R1M1, under anaerobic conditions,
      arg-2 showed light-induced proton extrusion concomitant with an increase in ATP
      level without transient proton uptake. Dicyclohexylcarbodiimide enhanced the rate
      and extent of proton extrusion and inhibited ATP formation in the light. The
      apparent stoichiometry of H+/ATP was estimated to be more than three in this
      natural bR+hR- strain.

PMID- 7803448
TI  - Changes in the distribution of the control of the mitochondrial oxidative
      phosphorylation in regenerating rabbit liver.
AB  - Applying the metabolic control theory, inhibitor titration studies were carried
      out on Complex I, III, IV, ATP synthase, ATP/ADP carrier and P(i) carrier of
      mitochondrial oxidative phosphorylation in normal and regenerating rabbit liver
      in order to examine the acceleration mechanism of mitochondrial oxidative
      phosphorylation. In regenerating rabbit liver the rate of state 3 respiration,
      respiratory control ratio and phosphorylation rate in the presence of mM
      glutamate, 250 microM ADP and 3 mM inorganic phosphate increased significantly as
      compared with the control by 73%, 48% and 76%, respectively. The control of the
      rate of state 3 respiration in normal liver was exerted by Complexes I, IV and
      steps other than the aforementioned six steps, whose flux control coefficients
      were 0.317, 0.214 and 0.469, respectively. By contrast, in regenerating liver,
      the control was more evenly distributed among these steps in oxidative
      phosphorylation and the possibility is suggested that Complexes I, IV and steps
      other than the six steps are activated during regeneration. The activation of
      Complexes I and IV was attributed to their increased activity, since it was not
      accompanied by an increase in the amount of the enzymes.

PMID- 7803449
TI  - Investigation of the ammonium chloride and ammonium acetate inhibition of oxygen
      evolution by Photosystem II.
AB  - Using EPR and EXAFS spectroscopies we show that high concentrations of ammonium
      cations at alkaline pH are required for (1) inhibition of oxygen evolution: (2)
      an alteration of the EPR properties of the oxygen evolving complex: (3) the
      ability to detect YZ; and (4) the slow reduction of the Mn complex leading to the
      appearance of EPR detectable Mn2+. The inhibition of S state cycling, slowing of
      YZ reduction, appearance of Mn2+ and the yield of a Hpp < 10 mT S3 type EPR
      signal are decreased by calcium addition. This indicates that these effects were
      probably associated with calcium depletion arising from the high concentration of
      ammonium cation. The ammonia-induced changes to the S2 multiline EPR signal are
      not affected by calcium addition. The appearance of Mn2+ is shown to be
      reversible on illumination, suggesting that the Mn reduced from the native state
      is located at or near the native site. Simulations of the interaction which give
      rise to the S3 EPR signal are also presented and discussed. These indicate that
      lineshape differences occur through small changes in the exchange component of
      the interaction between the manganese complex and organic radical, probably
      through minor structural changes between the variously treated samples.

PMID- 7803450
TI  - Topological studies of spinach 22 kDa protein of Photosystem II.
AB  - An intrinsic 22 kDa polypeptide is associated with the O2-evolving Photosystem II
      core complex in a variety of green plants, although it does not appear to be
      required for O2 evolution. Digestion of thylakoid membranes and isolated
      Photosystem II preparations with trypsin, followed by immunoblotting using
      spinach anti-22 kDa antibodies, leads to two observations: (1) the domain between
      the 2nd and 3rd transmembrane helices of the 22 kDa protein is stromally exposed,
      and (2) only in a reaction center complex preparation, lacking the chlorophyll
      a/b-light harvesting complex II, is there extensive proteolytic cleavage of the
      22 kDa protein. We also found that after, but not prior to, selective extraction
      of the 22 and 10 kDa proteins from Photosystem II membranes, the chlorophyll a/b
      light harvesting complex II can be separated from the Photosystem II reaction
      center core by precipitation with MgCl2. This result suggests that the 22 kDa
      polypeptide is located between the Photosystem II reaction center polypeptides
      and light-harvesting complex II; it is possible that the protein serves as a link
      between the two protein complexes. The presence of the 22 kDa protein in several
      species was also examined by immunoblotting with polyclonal spinach anti-22 kDa
      antibodies.

PMID- 7803451
TI  - Primary structure, cell-free synthesis and mitochondrial targeting of the 8.2 kDa
      protein of cytochrome c reductase from potato.
AB  - Cytochrome c reductase from potato comprises ten subunits with apparent molecular
      sizes between 55 and < 10 kDa. The subunit with the highest electrophoretic
      mobility on SDS-polyacrylamide gels was isolated and analysed by cyclic Edman
      degradation. Mixtures of degenerative oligonucleotides were derived from the
      obtained sequence data and used for the isolation of corresponding cDNA clones.
      The clones encode a protein of 72 amino acids which exhibits significant sequence
      identity with a 9.5 kDa subunit of cytochrome c reductase from bovine and a 11
      kDa subunit of the enzyme complex from yeast. Comparison between the deduced
      amino acid sequence of the open reading frame and the sequence of the mature
      protein reveals that only the initiator methionine is absent in the functional
      subunit. Hence the protein has a calculated molecular mass of 8.2 kDa.
      Transcripts of the potato 8.2 kDa protein were not translated in reticulocyte
      lysates but in vitro translation worked efficiently with wheat germ lysate.
      Import of the radiolabelled protein into isolated mitochondria from potato seems
      to depend on a potential across the inner membrane and confirms the absence of a
      cleavable mitochondrial presequence.

PMID- 7803452
TI  - Caffeine and Ca2+ stimulate mitochondrial oxidative phosphorylation in saponin
      skinned human skeletal muscle fibers due to activation of actomyosin ATPase.
AB  - The rate of mitochondrial oxidative phosphorylation of saponin-skinned human
      muscle fibers from m. vastus lateralis in the presence of glutamate, malate and
      ATP is reported to be sensitive to caffeine and to changes of free calcium ion
      concentration. An approximately twofold increase in respiration was observed by
      the addition of 15 mM caffeine, because of the efflux of calcium from
      sarcoplasmic reticulum. Direct addition of a Ca2+/CaEGTA buffer, containing 1.5
      microM free calcium ions had a similar effect. The ATP-splitting activity of
      skinned fibers was also stimulated by caffeine or calcium. These observations can
      be explained exclusively by the calcium-induced activation of actomyosin ATPase.
      (i) Thapsigargin, an inhibitor of the sarcoplasmic reticulum Ca(2+)-ATPase, had
      no influence. (ii) In myosin-extracted 'ghost' fibers containing intact
      mitochondria and an intact sarcoplasmic reticulum caffeine had a negligible
      effect on oxidative phosphorylation. (iii) The caffeine-induced increase in rate
      of fiber respiration was concomitant with a decrease in mitochondrial membrane
      potential and a decrease in the redox state of the mitochondrial NAD system. (iv)
      The calcium ionophore A 23187 caused a stimulation of respiration and ATP
      splitting activity, similar to caffeine. (v) The calcium dependencies of
      respiration and ATP splitting activity of saponin-skinned human muscle fibers
      were in experimental error identical. Therefore it is concluded that calcium
      efflux from sarcoplasmic reticulum affects oxidative phosphorylation in skeletal
      muscle mostly via the stimulation of actomyosin ATPase.

PMID- 7803453
TI  - Developmental regulation of tissue-specific isoforms of subunit VIa of beef
      cytochrome c oxidase.
AB  - The switching of the subunit VIa isoforms of cytochrome c oxidase has been
      followed in heart tissue during bovine development both by transcript levels and
      in terms of the incorporation of L- (liver) and H- (heart) polypeptides into
      mitochondria. In early fetuses, e.g., 60-days development, there are high levels
      of VIaL transcript and high levels of the VIaL polypeptide incorporated into
      mitochondria. In late fetuses (after 200 days), the levels of VIaL transcript are
      still high, with less but still significant amounts of VIaL polypeptide present
      in comparison to adult heart in which the amount of this isoform is negligible.
      As the proportion of VIaL transcript is reduced, the proportion of VIaH
      transcript increases along with the amount of the VIaH isoform in mitochondria.
      These data indicate isoform switching during late fetal development. The presence
      of COLBP (cytochrome oxidase liver isoform binding protein) (Preiss, T. and
      Lightowlers, R.N. (1993) J. Biol. Chem. 268, 10659-10667) was examined at
      different developmental stages. COLBP binding activity was observed in hearts of
      late fetuses but not found in adult heart tissue, providing a correlation between
      the presence of this factor and the presence of the VIaL polypeptide in
      mitochondria.

PMID- 7803454
TI  - Characteristics of mitochondrial proton leak and control of oxidative
      phosphorylation in the major oxygen-consuming tissues of the rat.
AB  - Maintenance of an electrochemical proton gradient across the mitochondrial inner
      membrane against the significant proton permeability of the membrane accounts for
      25-30% of resting oxygen consumption in hepatocytes. It has been proposed that
      proton leak could be a significant contributor to resting metabolic rate in
      mammals if it were present in other tissues. Mitochondria were isolated from the
      major oxygen-consuming tissues (liver, kidney, brain and skeletal muscle) of the
      rat. In each tissue, the mitochondria showed significant proton leak with the
      same characteristic non-linear dependence on membrane potential. Liver and kidney
      mitochondria showed similar membrane proton permeability per mg of mitochondrial
      protein; brain and muscle permeabilities were greater when expressed in this way.
      Differences in the kinetic response of the substrate oxidation and
      phosphorylating systems to membrane potential were observed. The substrate
      oxidation system was more active in kidney, brain and skeletal muscle
      mitochondria than in liver mitochondria per mg of mitochondrial protein. Liver
      and kidney phosphorylating systems were less active than brain and skeletal
      muscle per mg of mitochondrial protein. The control of oxidative phosphorylation
      was also assessed. The distribution of control in mitochondria isolated from the
      four tissue types was found to be similar.

PMID- 7803455
TI  - Identification of the iron-carbonyl stretch in distal histidine mutants of
      carbonmonoxymyoglobin.
AB  - Soret-excitation resonance Raman (RR) spectra are reported for six distal
      histidine mutants of carbonmonoxymyoglobin including H64A, H64V, H64L, H64I,
      H64W, and H64W/L29F. Based on 13CO isotope shifts, the iron-carbonyl stretching
      vibrations are unambiguously identified. The correct assignment of these modes
      eliminates the differences in the conformational substate occupations predicted
      by the RR versus IR data.

PMID- 7803456
TI  - Secondary structure of the 33 kDa, extrinsic protein of Photosystem II: a far-UV
      circular dichroism study.
AB  - The 33 kDa extrinsic protein of Photosystem II is an important component of the
      oxygen-evolving apparatus which functions to stabilize the manganese cluster at
      physiological chloride concentrations and to lower the calcium requirement for
      oxygen evolution. Chou-Fasman analysis of the amino-acid sequence of this protein
      suggests that this component contains a high proportion of alpha-helical
      structure and only relatively small amounts of beta-sheet structure. A
      computational study using more sophisticated techniques (Beauregard, M. (1992)
      Environ. Exp. Bot. 32, 411-429) concluded that the protein contained little
      periodically ordered secondary structure. In this study, we have directly
      measured the relative proportions of secondary structure present in the 33 kDa
      protein using far-ultraviolet circular dichroism spectroscopy. Our results
      indicate that, in solution, this protein contains a large proportion of beta
      sheet structure (38%) and relatively small amounts of alpha-helical structure
      (9%). A structural model of the 33 kDa protein based on a constrained Chou-Fasman
      analysis (Teeter, M.M. and Whitlow, M (1988) Proteins 4, 262-273) is presented.

PMID- 7803457
TI  - DNA sequence of the cut A, B and C genes, encoding the molybdenum containing
      hydroxylase carbon monoxide dehydrogenase, from Pseudomonas thermocarboxydovorans
      strain C2.
AB  - Pseudomonas thermocarboxydovorans strain C2 is capable of using carbon monoxide
      as the sole source of carbon and energy. The key enzyme for CO utilisation is the
      molybdenum containing iron-flavoprotein carbon monoxide dehydrogenase (CODH).
      This paper reports the DNA sequencing of a 4.7 kb region of the C2 genome which
      appears to encode the CODH enzyme. The genes for the three subunits of CODH,
      which we have named cut A, B and C, have been identified and they appear to form
      an operon. The predicted protein sequences of the three subunits have homology to
      the structurally related protein, xanthine dehydrogenase, from Drosophila
      melanogaster. By comparison with xanthine dehydrogenase it can be predicted that
      the molybdenum cofactor binds to the large subunit of CODH, the small subunit of
      CODH contains the iron-sulphur centers and the medium subunit binds FAD/NAD+.

PMID- 7803458
TI  - Nucleotide sequence of the psbE, psbF and trnM genes from the chloroplast genome
      of Chlamydomonas reinhardtii.
AB  - We have determined the nucleotide sequences of the psbE and psbF genes, which
      encode the alpha and beta subunits, respectively, of cytochrome b-559, from the
      chloroplast genome of the green alga Chlamydomonas reinhardtii. In contrast to
      other organisms psbE is not co-transcribed with psbF. The primary structures of
      the gene products are very similar to the equivalent proteins in cyanobacteria
      and plants. Each subunit contains a single histidine residue that is thought to
      ligate haem. Upstream of the psbE gene, a trnM gene is located which encodes an
      elongator tRNA(Met) molecule.

PMID- 7803459
TI  - Nucleotide sequence of the petB gene encoding cytochrome b6 from the mesophilic
      cyanobacterium Synechocystis PCC 6803: implications for evolution and function.
AB  - The gene encoding the cytochrome b6 subunit (petB) of the cytochrome b6f complex
      has been isolated, cloned and sequenced by nonradioactive methods from genomic
      DNA of the unicellular cyanobacterium Synechocystis sp. PCC 6803. The coding
      region consists of 666 nucleotides, coding for a polypeptide with a molecular
      mass of 25.02 kDa. In contrast to higher plant petB sequences an aminoterminal
      extension of seven amino acids occurs. Aminoterminal sequencing of the isolated
      protein excludes--different from higher plants--the existence of an intron after
      the first amino acids but indicate the posttranslational removal of three amino
      acids from the amino terminus. The aminoterminal extension--found only in non
      nitrogen-fixing, unicellular cyanobacteria--shows a high degree of homology
      between different species.

PMID- 7803460
TI  - Nucleotide sequence of the petE gene encoding plastocyanin from the
      photosynthetic prokaryote, Prochlorothrix hollandica.
AB  - We have determined the nucleotide sequence of the petE gene encoding plastocyanin
      from the chlorophyll a/b-containing photosynthetic prokaryote, Prochlorothrix
      hollandica. Comparison of the deduced amino acid sequence encoded by the gene
      with the N-terminal sequence of the purified protein revealed that plastocyanin
      is synthesized as a precursor bearing an N-terminal domain of 34 amino acids
      having some structural similarity to thylakoid lumenal transit peptides
      identified in other organisms. The mature protein has an apparent isoelectric
      point of 8.37 and a molecular mass of 10,236 Da.

PMID- 7803461
TI  - Teichuronic acid of the cell wall of Actinoplanes brasiliensis.
AB  - The cell wall of Actinoplanes brasiliensis INA 3802 contains a teichuronic acid
      of unusual structure, as determined in a nondestructive way by 1H- and 13C-NMR
      spectroscopy. The polysaccharide comprises six tetrasaccharide units of the
      following composition: -->6)-alpha-D-Glcp-(1-->4)-beta-D-2,3-diacetamido- 2,3
      dideoxyGlcpA-(1-->4)-alpha-D-2,3-diacetamido-2,3-dide oxyGlcp-(1-->4)-beta- D-2,3
      diacetamido-2,3-dideoxyManpA. A polymer of such structure has not heretofore been
      reported for procaryotic cell walls.

PMID- 7803462
TI  - Stereochemistry of 2,4-dimethyleicos-2-enoate from the pyruvylated glycolipid of
      Mycobacterium smegmatis.
AB  - The absolute stereochemistry of 2,4-dimethyleicos-2-enoic acid, isolated from the
      pyruvylated glycolipid of Mycobacterium smegmatis, has been determined. The two
      enantiomers of methyl 2,4-dimethyleicos-2-enoate were synthesised for the first
      time but could not be separated by gas chromatography on cyclodextrin phases. (E)
      2-Methyloctadec-2-enoate, an intermediate in the synthesis, is a characteristic
      component of acyl trehalose glycolipids from Mycobacterium fortuitum. Ozonolysis
      of the fatty acid ester mixture, obtained from the pyruvylated glycolipid
      produced 2-methyloctadecanoate. It was identified as the (S)-enantiomer by
      comparison with (2R) and (2S)-2-methyloctadecanoic acid, intermediates in the
      synthesis of (4R)- and (4S)-2,4,-dimethyleicos-2-enoic acid, using
      enantioselective gas chromatography of the methyl esters with heptakis(2,6-di-O
      methyl-3-O-pentyl)-beta-cyclodextrin as a chiral stationary phase. The natural
      acid was therefore determined to be 2E-(4S)-2,4-dimethyleicos-2-enoic acid.

PMID- 7803463
TI  - Molecular dynamics simulation of the rare amino acid LL-dityrosine and a
      dityrosine-containing peptide: comparison with time-resolved fluorescence.
AB  - The fluorescence of the rare amino acid LL-dityrosine, which is found in
      insoluble biological materials with structural features, was recently shown to
      decay non-exponentially (Kungl et al. (1992) J. Fluorescence 2, 63-74). Here we
      investigated the time-resolved fluorescence of a dityrosine-containing peptide
      (DCP) to study the influence of side chains on the fluorescence decay of the
      chromophore. The fluorescence decay of DCP was best fitted by three exponential
      terms including a sub-nanosecond rise term, the values of which are quite similar
      to the parameters obtained for the decay of free dityrosine. They were found to
      depend on the pH of the aqueous solution but not on the temperature. Analysis by
      an exponential series method revealed broad fluorescence lifetime distributions
      for DCP. Compared to the corresponding analysis of dityrosine transients, similar
      lifetime centers were found whereas the widths of the distributions were found
      broader for DCP. Molecular dyamics (MD) simulations of dityrosine at 300 K show
      that chi 1 and chi 2 side chain conformers (rotamers) of both tyrosine subunits
      interconvert on a picosecond timescale. The rates of interconversion were shown
      to depend critically upon the MD technique applied: in vacuo simulations yielded
      lower interconversion rates compared to stochastic dynamics (SD) and full MD
      (water explicitly included). However, MD simulations of the dityrosine-containing
      peptide revealed no interconversions of the chi 1 and chi 2 side chain rotamers
      of both tyrosine subunits within a 400 ps trajectory. Interconversions could be
      induced by raising the temperature of the system (DCP plus solvent) to 340 K.
      Side chain rotamers of dityrosine are not stable on a fluorescence time scale but
      are stable when a dityrosine-containing peptide is regarded. Nevertheless both
      molecules yield similar fluorescence decay patterns. We therefore conclude that
      the rotamer model proposed for the fluorescence decay of tyrosine and tryptophan
      cannot be applied to the fluorescence decay of dityrosine and peptides containing
      this chromophore. This should be of future interest when dityrosine is used as an
      intrinsic sensor to study complex dityrosine-containing macromolecules by
      fluorescence spectroscopy.

PMID- 7803464
TI  - Cell manipulation and cultivation under a.c. electric field influence in highly
      conductive culture media.
AB  - Extreme miniaturisation of electrodes enabled us to apply high-frequency electric
      fields (between 100 kHz and several hundred MHz) of field strengths up to 50 kV/m
      into cell suspensions of high conductivity (several S/m), such as original cell
      culture media. The active electrode areas were additionally decreased and
      modified by insulating the terminals and/or coating of the electrodes with thin
      dielectric layers. Micro scaled electrode structures were fabricated on glass or
      silicon wafers in semiconductor technology. It could theoretically and
      experimentally be shown that cells exhibit exclusively negative dielectrophoresis
      if suspended in highly conductive media. Therefore, they can be repulsed from
      surfaces by appropriate arrangements of electrodes and easily be manipulated in
      free solution. Adherently growing animal cells, like mouse fibroblasts (3T3,
      L929), were cultivated in Dulbecco's Modification of Eagle's Medium (DMEM) or
      RPMI 1640 under permanent field application (frequency: 10 MHz, field strength:
      50-100 kV/m).

PMID- 7803465
TI  - Glycosylation of yeast exoglucanase sequons in alg mutants deficient in the
      glucosylation steps of the lipid-linked oligosaccharide. Presence of glucotriose
      unit in Dol-PP-GlcNAc2Man9Glc3 influences both glycosylation efficiency and
      selection of N-linked sites.
AB  - The major exoglucanase (Exg) from Saccharomyces cerevisiae has a short N-linked
      oligosaccharide attached to each of the potential glycosylation sites present in
      the primary translation product. We have studied the Exg glycoforms secreted by
      alg mutants deficient in the final steps of the assembly of dolichol-P-P-GlcNAc2
      Man9-Glc3. These mutants synthesize and transfer to nascent proteins truncated
      oligosaccharides lacking two (alg8) or three (alg5 and alg6) glucoses. In
      addition to the enzyme carrying both sugar chains (ExgII), all three mutants
      secreted underglycosylated forms containing one oligosaccharide attached to
      either the first (ExgII'1/2) or the second (ExgII1/2) potential glycosylation
      site, and nonglycosylated enzyme (ExgTuni). As compared with alg5 and alg6, alg8
      secreted a higher proportion of ExgII, which was paralleled by a significant drop
      in the proportion of ExgTuni and, to a lesser extent, of ExgII1/2. The presence
      of a single glucose attached to Dol-P-P-GlcNAc2-Man9 therefore increases the
      efficiency of transfer of the that oligosaccharide to the protein acceptor in
      vivo. Moreover, whereas ExgII'1/2 was never secreted by wild type cells, it was
      the most abundant underglycosylated form secreted by all three mutants. These
      mutants are affected in the efficiency at which the individual sequons that are
      glycosylated, and this suggests a role for the glucotriose unit in the selection
      of the sequons are to be occupied in glycoproteins synthesized by wild type.

PMID- 7803466
TI  - Dextran sulfate binding to isolated rat glomeruli and glomerular basement
      membrane.
AB  - The binding of dextran sulfate to isolated glomeruli and glomerular basement
      membrane has been studied and compared to the glomerular uptake of dextran
      sulfate during isolated kidney perfusion. Two binding sites for [3H]dextran
      sulfate to isolated glomeruli could be identified at 37 degrees C; an high
      affinity site (KA = 4.76 x 10(6) M-1) (4.4 x 10(10) molecules/glomerulus) and a
      low affinity site (KA = 5.8 x 10(4) M-1) (2.0 x 10(11) molecules/glomerulus)
      whereas at 4 degrees C there was only an high affinity binding site (KA = 1.43 x
      10(6) M-1) (7 x 10(10) molecules/glomerulus). The glomerular binding of dextran
      sulfate appears to be to cellular elements as the binding sites were not present
      in purified glomerular basement membrane which effectively did not bind dextran
      sulfate. The binding of dextran sulfate to isolated glomeruli was far in excess
      of that found associated with glomerular uptake during isolated kidney perfusion.
      The difference has been discussed in terms of the different capillary wall
      surfaces exposed to the dextran sulfate and the concentration gradients that may
      exist in the two types of experiments. The structural integrity of the glomerulus
      is also important in governing the amount of binding as structural disintegration
      through freeze-thawing and sonication revealed more binding sites. These data may
      suggest a specific distribution of binding sites and specific transglomerular
      transport pathways where many of these sites are not exposed. The nature of
      binding [3H]dextran sulfate to isolated glomeruli was different to isolated
      perfused kidney glomerular uptake when studied in terms of the kinetics of
      exchange with unlabelled dextran sulfate. This exchange data suggests a passive
      binding mechanism in isolated glomeruli whereas in isolated kidney perfusion the
      nature of the exchange would suggest a glomerular intracellular uptake (Tay, M.,
      et al. (1991) Am. J. Physiol. 260, F549-F554).

PMID- 7803468
TI  - Fasciculin inhibition of acetylcholinesterase is prevented by chemical
      modification of the enzyme at a peripheral site.
AB  - Fasciculin 2 (FAS) is a 61 amino acid peptide present in Dendroaspis angusticeps
      snake venom, with a selective and potent inhibitory activity towards
      acetylcholinesterase (AChE). The specific interaction of FAS with peripheral
      sites present in Electrophorus electricus AChE (Ki = 0.04 nM FAS) was
      investigated by chemical modification with N,N-dimethyl-2-phenylaziridinium (DPA)
      in the presence of active or peripheral anionic site protective agents. An enzyme
      was obtained that compared to the native AChE is 10(6)-times less sensitive to
      FAS, is fully inhibited by edrophonium and tacrine, and is 25-170-times less
      sensitive to several peripheral site ligands. Characterization of catalytic
      functions showed that Km for acetylthiocholine was 4-fold lower in the DPA
      modified enzyme, whereas Km for phenylacetate remained the same. Values for Kcat
      determined with both substrates were unchanged. Diminished catalytic efficiency
      reflects that hydrolysis and/or supply of cationic substrates to the active site
      was affected by DPA reaction at a peripheral site. Previous data implicate Trp
      279 (Torpedo AChE sequence numbering) as the residue actually involved in DPA
      modification. Our results strongly support FAS binding to an AChE peripheral site
      which partially overlaps the site of other peripheral site ligands including
      acetylthiocholine.

PMID- 7803467
TI  - Further characterization of the gelatinase-containing particles of human
      neutrophils.
AB  - In addition to azurophil and specific granules, a third storage compartment is
      known to exist in the neutrophils. This compartment which consists of
      morphologically heterogeneous particles is characterized by a high specific
      activity in gelatinase. A gelatinase enriched fraction was prepared by
      subcellular fractionation of neutrophil homogenates using rate zonal
      centrifugation. This fraction was enriched in diamine oxidase. Among the proteins
      released from the neutrophils upon stimulation by formyl peptides, those
      belonging to the gelatinase enriched fraction were determined after removal of
      the proteins from specific and azurophil granules by selective immunoadsorption.
      Gelatinase was recovered together with tetranectin, beta 2-microglobulin and
      diamine oxidase in the same fraction. Differences in the kinetics of release of
      gelatinase and diamine oxidase versus vitamin B-12-binding protein suggest that
      the proteins belong to distinct subcellular structures.

PMID- 7803469
TI  - Identification of genetic events involved in early steps of immortalization of
      mouse fibroblasts.
AB  - The spontaneously immortalized early passaged fibroblasts from three different
      strains of mouse are observed to represent two distinct stages of
      immortalization. The cells at stage I are characterized by slow growth rate,
      contact inhibition and requisition of serum factors for their growth and
      proliferation. Stage II cells are marked by fast, multilayer growth that is
      independent of serum supplementation in growth medium and by the elevated levels
      of the two marker proteins, i.e., p53 and p81. The change from cytosolic
      distribution of mortalin, a senescence inducing protein (J. Biol. Chem. (1993)
      268, 6615-6621; 22239-22242) to the perinuclear locale is detected as an early
      event during cellular immortalization. Furthermore, the distinct stages could be
      characterized by thermal analysis of intact cells, that to the best of our
      knowledge is employed for the first time for the analysis of cellular mortal and
      immortal phenotypes. The study characterizes at least two distinct end points in
      rodent transformation suggesting that there are multiple routes to
      immortalization.

PMID- 7803470
TI  - Characterization of distinct forms of methionine adenosyltransferase in
      nucleated, and mature human erythrocytes and erythroleukemic cells.
AB  - Two peaks of methionine adenosyltransferase (MAT) activity from human
      erythrocytes were partially purified on a DEAE-cellulose column. Using anti-MAT
      antibodies, a 60 kDa form of MAT, referred to as rho was identified in peak I.
      Although rho represented the major MAT protein in crude erythrocyte extracts, the
      enzyme was very labile and accounted for only 6% of the total MAT activity. Peak
      II enzyme was stable, and consisted of the previously described catalytic alpha
      (53 kDa) subunit and the beta subunit (38 kDa), both of which are found in
      activated human lymphocytes and leukemic cells of lymphoid origin. Mature normal
      and polycythemic erythrocytes contained predominantly rho as the major MAT
      protein, while nucleated erythrocytes and reticulocytes contained predominantly
      the lambda (68 kDa), the major form found in resting human lymphocytes. Human
      erythroleukemic cells (HEL 92.1.7) contained the alpha, alpha' and beta subunits
      of MAT, and in this regard was indistinguishable from MAT found in activated
      lymphocytes and leukemic cells of lymphoid origin (Jurkat). Since rho was
      generated during the incubation of extracts from resting lymphocytes, which
      contain predominantly lambda, in the absence of protease inhibitors; the rho form
      of MAT appears to be derived from the lambda form by proteolytic cleavage. The
      data indicate that distinct forms of MAT are present at different stages of
      erythrocyte maturation and reveal the presence of a new form of MAT with reduced
      activity compared to previously described forms.

PMID- 7803471
TI  - Molecular cloning and functional expression of a mouse cytochrome P-450 (Cyp3a
      13): examination of Cyp3a-13 enzyme to activate aflatoxin B1 (AFB1).
AB  - A cDNA encoding a novel member of the cytochrome P-450 superfamily, Cyp3a-13, has
      been isolated from mouse liver cDNA library by hybridization screening. The Cyp3a
      13 encoded 503 amino acid residues and shared 71% amino acid identity with Cyp3a
      11. When Cyp3a-13 cDNA was expressed in CR119 cells which had been established as
      a cell line stably expressing NADPH-cytochrome P-450 reductase cDNA of guinea
      pigs, aflatoxin B1-dependent cytotoxicity was observed. This cytotoxicity was
      enhanced by alpha-naphthoflavone (7,8-benzoflavone), which is known to augment
      the CYP3A enzymatic activity. The results indicate that CYP3A in mice, which are
      relatively insensitive to aflatoxin B1, can activate aflatoxin B1 to a genotoxic
      product.

PMID- 7803473
TI  - The growth of Escherichia coli in glucose-limited chemostat cultures: a re
      examination of the kinetics.
AB  - The relationship between specific growth rate (mu) and steady-state glucose
      concentration was investigated for Escherichia coli ML30 in carbon-limited
      chemostat culture. This was made possible by the development of a method for
      measuring reducing sugars in culture media in the microgram.1-1-range. Cells
      initially cultivated in batch culture at high glucose concentrations required
      long-term adaptation to nutrient-limited growth conditions in the chemostat
      (between 100-200 volume changes at D = 0.6 h-1) until steady-state with respect
      to residual glucose concentration was reached; for adapted cells, however, new
      steady-state glucose concentrations were usually obtained within less than 10
      volume changes. A statistical evaluation of different kinetic models showed that
      between 0.2 h-1 < D < 0.8 h-1 the three models proposed by Monod (1942), Shehata
      and Marr (1971), and Westerhoff et al. (1982) described the data equally well and
      the applicability of the different models is discussed. Depending on the model
      used, calculated glucose concentrations supporting half maximum growth rate (Ks)
      were in the range of 40-88 micrograms.1-1. The data strongly suggest that the
      large differences in Ks constants reported in the literature (ranging from 40
      micrograms.1-1 up to 99 mg.1-1) are due to the use of E. coli cells adapted to
      different degrees to nutrient-limited growth conditions. This indicates that it
      is probably not possible to describe the kinetic properties of a bacterium with a
      single set of kinetic 'constants'.

PMID- 7803472
TI  - Effect of alcohol on the activity and subcellular distribution of phosphatidate
      phosphohydrolase in rat liver.
AB  - The activity and subcellular distribution, before and after translocation with
      oleic acid, of hepatic phosphatidate phosphohydrolase (PAH: E.C.3.1.3.4) was
      measured following acute and chronic administration of ethanol with either 18% or
      4.4% total calories as fat, to male Wistar rats. Acute injection produced a
      significant increase in PAH activity, without affecting the subcellular
      distribution or translocation of activity from the cytosol into the membraneous
      compartments induced by oleic acid. PAH activity, subcellular distribution and
      the translocation of activity by oleic acid was similar in all groups following
      chronic liquid feeding. Chronic ethanol feeding was associated with significantly
      increased plasma corticosterone in the ethanol-fed rats compared with controls,
      independent of the fat content of the diet. Plasma insulin was similar in chronic
      alcohol fed rats and controls. This suggests that enhanced PAH activity may
      contribute to triacylglycerol accumulation following acute alcohol injection, but
      activity normalises as hepatic lipid accumulation progresses and this effect is
      not due to attenuation of the hormonal effects of ethanol.

PMID- 7803475
TI  - Regulation of neutrophil activation by oleic acid.
AB  - Physiological concentrations of oleic acid inhibited C5a-induced myeloperoxidase
      release from neutrophils. The inhibition occurred promptly following the addition
      of oleic acid, was dose-dependent and saturable, and was greater at low
      concentrations of C5a. Kinetic analysis of the curve for 1/myeloperoxidase
      release against 1/[C5a] in the presence of oleic acid, was compatible with a
      cooperative pattern of interaction. The inhibitory effect persisted after
      repeated washings of cells preincubated with oleic acid. The effect of oleic acid
      was not specific for C5a-induced neutrophil activation; oleic acid also inhibited
      myeloperoxidase release induced by the Ca2+ ionophore A-23187, as well as zymosan
      activated serum-induced chemotaxis. In experiments designed to localize the site
      of action of oleic acid on neutrophil activation, an intracellular oleic acid
      binding protein M(r) = 13,000) was isolated. The results suggest that acute
      changes in plasma fatty acid levels may have significant effects on neutrophil
      function under physiological conditions.

PMID- 7803474
TI  - Physical and chemical interactions between nitric oxide and nitroxides.
AB  - The physical and chemical interaction of nitric oxide (NO) with stable nitroxides
      have been studied in both aqueous and membrane environments. The ESR spectrum of
      3-carbamoyl-2,2,5,5-tetramethyl-3-pyrroline-1- yloxy (CTPO) was observed to
      broaden upon exposure to NO. This effect can be explained by invoking Heisenberg
      spin exchange as has been previously reported for molecular oxygen. No loss of
      total spin was observed negating the possibility of a chemical reaction between
      NO and CTPO. The extent of signal broadening was proportional to the
      concentration of NO and can thus be used to monitor NO concentration. We have
      used this method to observe the partitioning of NO into model membranes. We also
      report the use of multiquantum ESR to detect directly the effects of NO on the
      membrane bound spin label 12-doxylstearic acid. This methodology may prove useful
      for detecting NO in both aqueous and lipid environments and for examining the
      physical properties of NO within biological membranes.

PMID- 7803476
TI  - Peptidyl thioamides as substrates and inhibitors of papain, and as probes of the
      kinetic significance of the oxyanion hole.
AB  - The interaction of papain with a series of amide and thioamide substrates was
      studied to assess the contribution of the oxyanion hole to catalysis. Amides 1a
      4a (AcPheGly-NHR, where R = H, CH3, PhCH2 or p-O2NC6H4, respectively) were all
      hydrolyzed to AcPheGly-OH with kcat/Km values from 23-430 M-1s-1 (25 degrees C,
      20% v/v MeCN in 50 mM phosphate buffer, pH 6.3). Structurally analogous
      thioamides 1b-3b (AcPheGlyTNHR) were not detectably hydrolyzed by papain, but 4b
      (AcPheGlyTNHC6H4NO2) was hydrolyzed to the thiolacid AcPheGly-SH (kcat/Km = 2125
      M-1s-1). The latter was hydrolyzed further to AcPheGly-OH in a slower reaction.
      Thioamides 1b-3b bound to papain and inhibited the papain-catalyzed hydrolysis of
      Z-Gly-ONp, but the inhibition was generally less than 50% at concentrations up to
      500 microM, suggesting that the binding was purely non-covalent. The inability of
      papain to hydrolyze 1b-3b while 1a-3a are excellent substrates suggests that the
      oxyanion hole plays an important role in amide hydrolysis by papain. The facile
      hydrolysis of thioamide 4b was attributed to decreased amide bond resonance (i.e.
      a more reactive ground state) caused by the strong electron-withdrawing effect of
      the p-nitrophenyl substituent.

PMID- 7803477
TI  - Duplex and triplex directed DNA cleavage by oligonucleotide-Cu(II)/Co(III)
      metallodesferal conjugates.
AB  - Cu(II) desferal conjugated to d(T)10 at 5'-end is shown to direct the cleavage of
      single stranded 19-mer target DNA d(TA1GCCCGGCG), with a base preference G > C >>
      A. In contrast, the corresponding Co(II)-desferal conjugate directed the cleavage
      specific to only G sites (G12, G16, G17 and G19). Triplex targetting on the
      duplex 5'-TCCTGATAAAGGAGGAGATGAAGAAAAAATGA-3': 3'
      AGGACTATTTCCTCCTCTACTTCTTTTTTACT-5', using Cu(II) desferal conjugated to 5'-end
      of 3'-TTTCCTCCTCT-5' directed the cleavage at G5.

PMID- 7803478
TI  - Kinetic analysis of the intracellular conjugation of monochlorobimane by IC-21
      murine macrophage glutathione-S-transferase.
AB  - Monochlorobimane (MCB) reacts with glutathione (GSH) in a reaction catalyzed by
      the glutathione-S-transferase (GST) isozymes. The diffusion of MCB through cell
      membranes is rapid and the fluorescence conjugates are relatively insensitive to
      quenching and to pH effects, and are expelled slowly from the cell, allowing the
      rate of fluorescence increase to be used to probe the dynamics of the
      intracellular reaction. Using low-light microscopic cytometry to monitor the
      initial rates of fluorescence increase for the GST-catalyzed reaction within IC
      21 macrophages yields Vmax = 8.4 x 10(-16) mol s-1 cell-1 and KMCBm = 65 microM.
      Combining these data with an integrated Michaelis analysis of the reaction course
      yields KIP approximately 1.5 x 10(-5) M, and KmGSH approximately 3.0 x 10(-4) M
      (at [MCB] = 50 microM). The values of Vmax and KMCBm for the cell-free
      (extracellular) GST-catalyzed conjugation reaction are 1.2 x 10(-18) mol s-1 cell
      1 and 3.1 microM, respectively. The values of Vmax for the intra- and
      extracellular conjugation reactions differ by 700-fold, suggesting the presence
      of an intracellular activator for this enzyme system.

PMID- 7803479
TI  - A new S-adenosylmethionine decarboxylase from soybean axes.
AB  - A new active S-adenosylmethionine decarboxylase (EC 4.1.1.50) (SAMDC II) was
      extracted from soybean (Glycine max) axes. The enzyme was purified to homogeneity
      by ammonium sulfate fractionation, DEAE-Sepharose and
      methylglyoxalbis(guanylhydrazone) (MGBG)-Sepharose 6B chromatographies. The
      molecular weight of the native enzyme was 110,000, while the subunit molecular
      weights were 66,000 and 58,000, indicating a heterodimeric structure. The Km
      value of the enzyme for S-adenosylmethionine was 16 microM, which is two times
      higher than that of previously reported S-adenosylmethionine decarboxylase (SAMDC
      I) (8.1 microM). The specific activity of SAMDC II during the seed growth
      increased rapidly and reached its maximum on the second day after germination
      whereas that of SAMDC I reached its peak on the fourth day. MGBG was shown to
      inhibit SAMDC II competitively like SAMDC I. Carbonyl and sulfhydryl group
      specific reagents modified SAMDC II, resulting in the loss of enzymatic activity.
      Agmatine, the product of arginine decarboxylation catalyzed by arginine
      decarboxylase, inhibited the SAMDC II competitively (Ki = 40 microM) while it
      inhibited the SAMDC II non-competitively (Ki = 600 mM). The possible role of the
      chronological appearance of SAMDC II and SAMDC I, and properties of the enzyme
      are briefly discussed in connection with polyamine biosynthesis in soybean axes.

PMID- 7803480
TI  - Purification and characterization of eukaryotic translational initiation factor
      eIF-2B from liver.
AB  - Eukaryotic initiation factor (eIF)-2B was purified to greater than 95%
      homogeneity from both rat and bovine liver. The purified protein consisted of
      five nonidentical subunits with apparent molecular weights ranging from 30.9 to
      89.1 kDa. The holoprotein was characterized in terms of its Stokes radius and
      frictional coefficient. The isoelectric points for the beta-, gamma-, and epsilon
      subunits were found to be 6.4, 6.9, and approximately 6.0, respectively; the
      alpha- and delta-subunits did not focus well because their isoelectric points as
      predicted by the nucleotide sequences of cDNAs for the two proteins are greater
      than 8.5. The purified protein was used as antigen to generate monoclonal
      antibodies to the epsilon-subunit. The eIF-2B epsilon monoclonal antibodies and
      monoclonal antibodies to the alpha-subunit of eIF-2 were then used to directly
      quantitate the amounts of eIF-2B and eIF-2 in rat liver and rat reticulocytes.
      The ratio of eIF-2B to eIF-2 was found to be approx. 0.6 and 0.3 in liver and
      reticulocytes, respectively, supporting the proposition that phosphorylation of
      only part of the total cellular eIF-2 could potentially sequester all of the eIF
      2B into an inactive eIF-2.eIF-2B complex. The purified protein was also used as
      substrate in protein kinase assays. Extracts of rat liver were shown to contain
      protein kinase activity directed toward the epsilon-subunit, but no other subunit
      of eIF-2B. Overall, the studies presented here are the first to show a direct
      quantitation of eIF-2 and eIF-2B in different tissues. They also provide evidence
      that the epsilon-subunit of eIF-2B is the only subunit of eIF-2B that is
      phosphorylated by protein kinase(s) present in extracts of rat liver.

PMID- 7803481
TI  - A potent antihemorrhagin in the serum of the non-poisonous water snake Natrix
      tessellata: isolation, characterization and mechanism of neutralization.
AB  - The main natural antihemorrhagic factor (NtAH), which inhibits the hemorrhagic
      activity of Bothrops asper snake venom, was isolated from the serum of the non
      poisonous water snake Natrix tessellata by ammonium sulfate precipitation at 35
      55%, Sephadex G-75 gel filtration, ion exchange chromatography on DEAE-Sepharose
      and CM-Sepharose and hydrophobic Phenyl-Sepharose chromatography. The purified
      protein showed one band with an isoelectric point of 4.5 and a molecular mass of
      about 880 kDa. The antihemorrhagic activity was stable between pH 5.5-11.7 and up
      to 50 degrees C, but lost activity after 20 min at 60 degrees C. It did not form
      a precipitin line with the main hemorrhagin of Bothrops asper snake venom (BaH1),
      nor with the whole venom, which suggests that the antihemorrhagic factor is not
      an immunoglobulin. The mechanism of neutralization by the isolated
      antihemorrhagic factor NtAH did not include digestion of the hemorrhagic toxin
      BaH1. Chromatography of NtAH with active 125I-labeled BaH1 toxin as well as ELISA
      experiments demonstrated that the mechanism of neutralization involves formation
      of an inactive soluble complex between the natural NtAH of the non-poisonous
      water snake and the main hemorrhagin of Bothrops asper venom.

PMID- 7803482
TI  - Phytanic acid alpha-oxidation in rat liver mitochondria.
AB  - The alpha-oxidation of phytanic acid in rat liver is a mitochondrial function.
      The inhibition of phytanic acid oxidation activity by inhibitors of acyl-CoA
      ligases (Naproxen and Triacsin C) and that of carnitine acyltransferase I (2-(5
      (4-chlorophenyl)pentyl)oxirane-2 carboxylic acid (POCA) and 2-bromopalmitate) and
      increase in phytanic acid oxidation activity by the addition of exogenous
      carnitine and CoA to purified mitochondria suggests that phytanoyl-CoA ligase and
      carnitine acyltransferase I are essential for the activation and transport of
      phytanic acid across the mitochondrial membrane. This was further supported by
      the fact that activation of phytanic acid to phytanoyl-CoA was required only in
      intact mitochondria but not in mitochondria permealized with digitonin.
      DesulfoCoA, Naproxen and POCA treatment resulted in a significant decrease in
      phytanic acid oxidation in intact mitochondria but not in digitonin permealized
      mitochondria. These results show that alpha-oxidation of phytanic acid to
      pristanic acid, in contrast to beta-oxidation of fatty acids, requires free fatty
      acid as substrate. The inhibition of alpha-oxidation (approximately 90%) of
      phytanic acid by different cytochrome P-450 enzyme inhibitors indicated that
      alpha-oxidation of phytanic acid is mediated through cytochrome P-450 containing
      enzyme system. Similar to the omega-hydroxylation system in endoplasmic
      reticulum, alpha-hydroxylation and the subsequent alpha-oxidation of phytanic
      acid in mitochondria is induced by ciprofibrate, a hypolipidemic drug.

PMID- 7803483
TI  - The effects of glutathione and ascorbic acid on the oxidations of 6-hydroxydopa
      and 6-hydroxydopamine.
AB  - The interactions of ascorbic acid (AA) and reduced glutathione (GSH) in the
      oxidations of the catecholaminergic neurotoxins 6-hydroxydopa (TOPA) and 6
      hydroxydopamine (6-OHDA) were investigated by both high performance liquid
      chromatography with electrochemical detection (HPLC-ED) and spectrometric
      methods. These comparative studies showed TOPA and 6-OHDA to be extremely
      unstable, with 100% of the trihydroxyphenyls oxidized within 0.5 min at
      physiological pH in potassium phosphate buffer. Neither AA nor GSH was found
      capable of significantly impeding the oxidations of these trihydroxyphenyls, or
      of regenerating these substances by reducing back their oxidation products, even
      though such a redox exchange mechanism was demonstrated for AA and the
      dihydroxyphenyl dopamine. Although ineffective in keeping TOPA and 6-OHDA as
      reduced molecules, GSH may nevertheless influence the neurotoxicity of
      trihydroxyphenyls by interacting with their oxidation products forming
      glutathionyl conjugates, thereby switching the reaction pathway away from
      potentially toxic eumelanin precursors and toward the production of pheomelanin.
      Electrochemical analyses established the formation of two oxidation products
      derived from each trihydroxyphenyl, one detected at -100 mV and the other at +700
      mV. AA had no effect on either oxidation product, whereas GSH significantly
      decreased the levels of both oxidation products. The component detected at +700
      mV is the cyclized, reduced leukochrome. The identity of the component detected
      at -100 mV was not established, but it is considered to be either the p-quinone
      or the cyclized, oxidized aminochrome.

PMID- 7803484
TI  - Chemical and biological characterization of oxo-eicosatetraenoic acids.
AB  - Eicosatetraenoates (ETEs) with 5-oxo residues are known to induce human
      neutrophil (PMN) Ca2+ transients and chemotaxis. We find that 5-oxoETE, 5-oxo-8
      trans-ETE, 5-oxo-15-hydroxy-ETE, 5-hydroxy-ETE, 5-hydroxy-15-oxoETE, 5,15
      dioxoETE, and 5,15-dihydroxy-ETE have respective relative potencies of 10, 5, 3,
      1, 0.2, 0.1, and 0.02 in: a) causing PMN to mobilize Ca2+, aggregate, and release
      small amounts of granule enzymes and b) promoting large degranulation and
      oxidative burst responses in PMN co-challenged with platelet-activating factor,
      tumor necrosis factor-alpha, or ATP. Contrastingly, 12(R)-hydroxy-ETE, 12(S)
      hydroxy-ETE, and 12-oxoETE induced PMN Ca2+ transients and aggregation
      [respective potencies (5-hydroxy-ETE = 1) of 0.1, 0.01, and 0.003] but did not
      effect degranulation, and 15-hydroxy-ETE, 15-oxoETE, and 15-oxo-11-trans-ETE were
      inactive in all assays. Finally, 5-oxo/hydroxy-ETEs desensitized PMN to
      themselves but not to 12-oxo/hydroxy-ETEs or leukotriene (LT)B4; 12-oxo/hydroxy
      ETEs and LTB4 desensitized PMN to themselves and each other but not to 5
      oxo/hydroxy-ETEs; 15-oxo/hydroxy-ETEs did not desensitize PMN; and a LTB4
      receptor antagonist blocked responses to LTB4 and 12-oxo/hydroxy-ETEs but not to
      5-oxo/hydroxy-ETEs. Thus, 5-oxo/hydroxy-ETEs act by a common, LTB4 receptor
      independent mechanism that recognizes 5- but not 12- or 15-oxo/hydroxy-ETEs and
      prefers oxo over hydroxy residues at C5 whereas 12-oxo/hydroxy-ETEs act via a
      LTB4 receptor mechanism that recognizes 12- but not 5- or 15-oxo/hydroxy-ETEs and
      prefers hydroxy over oxo residues at C12.

PMID- 7803485
TI  - 3-Aminobenzamide enhances dexamethasone-mediated mouse thymocyte depletion in
      vivo: implication for a role of poly ADP-ribosylation in the negative selection
      of immature thymocytes.
AB  - 3-Aminobenzamide (3-ABAm), an inhibitor of poly ADP-ribosylation, was here found
      to remarkably enhance the dexamethasone (Dex)-mediated depletion of total mouse
      thymocytes within 24 h post-injection, when given i.p. in combination with Dex.
      After treatment the total thymocytes were fractionated by Percoll gradient
      centrifugation into two mitogen-unresponsive (high- and medium-density) and one
      mitogen-reactive (low-density) subpopulations and these were analyzed for the
      phenotypic expression of CD4 and CD8 antigens. Treatment with Dex alone most
      extensively depleted the high- and medium-density thymocytes and also those
      expressing both CD4 and CD8 double positive (DP) phenotypes in all three
      subpopulations. The CD4+ and CD8+ single positive (SP) and CD4-CD8- double
      negative (DN) subsets, in the low-density subpopulation in particular, were most
      resistant to the Dex-mediated depletion, thus giving rise to an enrichment of SP
      (2-fold) and particularly DN subset in the medium- and low-density populations (5
      fold) recovered. 3-ABAm, which alone increased the total thymocyte number up to 2
      fold, had no effect on the distribution of phenotypic subsets. However, the
      inhibitor, when given in combination with Dex, additionally depleted all four
      phenotypic subsets up to one-third of the levels with Dex alone, except for those
      of medium-density subpopulation. Because the non-inhibitor, 3-aminobenzoate, had
      no potentiating effect, our present results, together with our previous in vitro
      studies, indicate a role for the DNA repair cofactor poly ADP-ribose in the
      intrathymic death by apoptosis and depletion of thymocytes, especially those of
      DP subset in the high-density, functionally immature population.

PMID- 7803486
TI  - Modulation of ornithine aminotransferase activity by oxygen in rat hepatocyte
      cultures.
AB  - In hepatocytes in culture, ornithine aminotransferase activity remained higher
      when the cells were cultured at low oxygen tension (5%) than at high tension
      (21%), that is, it was higher in hepatovenous conditions. Northern blot analysis
      showed that the amount of the specific mRNA for the enzyme was also higher.
      Results of experiments performed in the presence of CoCl2, to replace the central
      Fe2+ in heme, or succinylacetone, to inhibit heme synthesis, support the view
      that a heme protein participates in the regulation of ornithine aminotransferase
      activity by oxygen. The oxygen sensor does not appear to act through
      phosphorylation by kinase C, as TPA has no significant effect on the process, but
      a phosphorylation dependent on cAMP might be involved.

PMID- 7803487
TI  - L-carnitine and some of its analogs delay the onset of apoptotic cell death
      initiated in murine C2.8 hepatocytic cells after hepatocyte growth factor
      deprivation.
AB  - Addition of L-carnitine and some of its analogs to low-serum incubation medium of
      murine hepatocytic C2.8 cells prolonged maintenance of life and enhanced cell
      growth, as compared to controls. The drug acted synergistically with hepatocyte
      growth factor (HGF). Addition of L-carnitine to cells that had grown confluently
      in medium supplemented with HGF, significantly delayed the onset of cell death
      (apoptosis) initiated after HGF deprivation. Protection by L-carnitine was dose
      dependent and stereospecific. Similar findings were obtained with three analogs
      of L-carnitine (i.e. isovaleryl-L-carnitine-HCl, isovaleryl-L-carnitine acid
      fumarate and butyryl L-carnitine taurine amide). In contrast, four different
      analogs (i.e. isovaleryl-L-carnitine-eptyl-ester-HCl, isovaleryl-L-carnitine
      idroxy-butyric-HCl, L-threonyl-L-carnitine-HCl and L-paramethyl-cinnamoil
      carnitine-HCl) were inactive. Although the mechanism of cytoprotection stimulated
      by L-carnitine remains unresolved, the data suggest that this compound serves as
      a co-factor that influences C2.8 cells to become less susceptible to damaging
      actions of noxious agents or conditions initiated after HGF withdrawal.

PMID- 7803488
TI  - Lack of inhibition by dideoxy-forskolin and verapamil of DIDS-sensitive volume
      activated Cl- secretion in human squamous lung carcinoma epithelial cells.
AB  - The effect of osmotic stress on Cl- permeability in human squamous lung carcinoma
      epithelial (S1) cells was investigated using a macroscopic 125I efflux assay.
      Hypotonic challenge of monolayers led to a significant (P < 0.01) dose-related
      increase in efflux from pre-loaded cells, returning to pre-activation rates
      within 10 min. A similar magnitude of response could be produced by challenge
      with an isotonic low chloride-containing solution. Neither 100 mM dideoxy
      forskolin nor 100 mM verapamil inhibited the increase in Cl- secretion after
      hypotonic challenge, whereas 100 mM DIDS inhibited volume-activated Cl- secretion
      by 55%. Both Northern and Western blot analysis confirmed the absence of MDR1
      mRNA and P-glycoprotein in the S1 cells. We conclude that these cells have a
      volume-regulated Cl- secretory pathway that is independent of the ABC
      transporter, P-glycoprotein.

PMID- 7803489
TI  - The metabolism of vitamin A to 3,4-didehydroretinol can be demonstrated in human
      keratinocytes, melanoma cells and HeLa cells, and is correlated to cellular
      retinoid-binding protein expression.
AB  - Conversion of retinol to 3,4-didehydroretinol is probably a rate-limiting step in
      the formation of 3,4-didehydroretinoic acid, a candidate ligand for nuclear
      retinoid receptors in human epidermal keratinocytes. To investigate whether this
      metabolic pathway also exists in other cell systems, we compared the retinoid
      concentrations and the bioconversion of [3H]retinol to [3H]3,4-didehydroretinol
      in human primary keratinocytes, human cervical carcinoma (HeLa) cells, human
      melanoma (JKM86-4) cells, monkey kidney epithelium (CV-1) cells, and murine
      teratocarcinoma (F9) cells. The cellular retinol concentration ranged from 2.33
      to 99.1 pmol/mg protein with the highest values observed in keratinocytes. 3,4
      Didehydroretinol was only detected in cells of human origin and its concentration
      ranged from 0.24 pmol/mg in HeLa to 34.6 pmol/mg in the keratinocytes. Incubation
      with [3H]retinol for 1-24 h resulted in a rapid appearance of [3H]3,4
      didehydroretinol in human keratinocytes, and to a lesser extent in HeLa and
      melanoma cells, but not in the other cells. Analysis of cellular retinol- and
      retinoic acid-binding protein concentrations showed a correlation to the cells'
      ability to accumulate 3,4-didehydroretinol, suggesting a role for these proteins
      in the 3,4-didehydro metabolic pathway. The combined results suggest that
      although 3,4-didehydroretinol is most typical for human keratinocytes, studies of
      its metabolism are also feasible in HeLa cells which contain low levels of
      retinoid-binding proteins.

PMID- 7803490
TI  - Conductive cation transport in apical membrane vesicles prepared from fetal lung.
AB  - In order to characterise the apically-located conductive cation pathway of the
      type II pneumocyte, apical plasma membranes were prepared from mature fetal
      guinea pig lung. The protocol yielded purified apical membranes that enriched 19
      fold with the brush border enzyme marker alkaline phosphatase; there was no
      significant contamination with other cellular membranes. A technique for imposing
      an outwardly-directed electrochemical Na+ gradient was used to amplify conductive
      22Na+ uptake into vesicles. Uptake of 22Na+ was time-dependent, proportional to
      the magnitude of the Na+ gradient, specific and sensitive to the amiloride
      analogues phenamil and EIPA (apparent minimum Ki values of 50 nM and 10 microM,
      respectively, with maximum uptake inhibition of 42% and 39% at 100 microM).
      Uptake experiments in which the outwardly-directed Na+ gradient was replaced by
      outwardly-directed gradients of small monovalent cations and molecular cations
      were performed. The Na+/K+ permeability ratio was 1.2:1, and over the extended
      range of small monovalent cations, a permeability sequence of Na+ > K+ > Li+ >
      Rb+ > Cs+ was observed, indicating the presence of fixed negative charge in or
      spatially close to the pore. The molecular cation permeability sequence of NH4+ >
      methylamine+ > dimethylamine+ > choline+ > N-methyl-D-glucamine+ >
      tetraethylammonium+ > tetramethylammonium+, after transformation, gives an
      estimate of 8 A for the conducting pore diameter. These data are consistent with
      the presence in the apical membrane of fetal type II pneumocytes of a cation
      specific channel with low Na+ selectivity and amiloride sensitivity.

PMID- 7803491
TI  - Enhanced expression of multiple forms of VEGF is associated with spontaneous
      immortalization of murine fibroblasts.
AB  - The mechanism(s) involved in immortalization that constitute the first step
      during malignant transformation has been the subject of our interest. By the use
      of spontaneously immortalized mouse embryonic fibroblasts we have earlier
      identified two stages of immortalization which are characterized by growth
      characteristics of the cells, their conditioned medium and the protein markers
      such as p53, p81 and mortalin (Kaul et al. (1994) Biochim. Biophys. Acta, in
      press). The present study was planned to purify the mitogenic factors from the
      conditioned medium of stage II cells. Sequential purification by chromatography
      followed by peptide sequencing has characterized one of these as vascular
      endothelial growth factor (VEGF). Further analysis by RT-PCR suggests that the
      spontaneously immortalized stage II fibroblasts have enhanced synthesis and
      secretion of VEGF as compared to their mortal parent cells. Expression of a novel
      304 bp long form of VEGF is identified in immortal fibroblasts in addition to the
      three known alternatively spliced forms. The study points to the involvement of
      VEGF function during spontaneous immortalization of mouse embryonic fibroblasts.

PMID- 7803492
TI  - Expression of glycolytic isozymes in rat thymocytes during cell cycle
      progression.
AB  - The time courses of activities of aldolase, glyceraldehyde-3-phosphate
      dehydrogenase, hexokinase and pyruvate kinase were determined in stimulated rat
      thymocytes at 24 h intervals during a period of 72 h of culture. In parallel the
      mRNA levels of these enzymes were analysed by Northern blotting with specific
      probes. Both the enzyme activities and the corresponding mRNA levels reached
      their maxima 48 h after stimulation coinciding with the S-phase of the cell
      cycle. The isozyme types of aldolase and hexokinase in resting and in mitogen
      stimulated rat thymocytes were identified by Northern blot hybridisation using
      isozyme-specific probes. In these cells the aldolase A is expressed, whereas type
      B and C could not be detected. The transcription of the aldolase A gene can be
      regulated by two different promoters. Depending on the alternative usage of the
      promoters the aldolase A-specific mRNA either contains the non-translated exons
      M1 or AH1. In rat thymocytes the promoter proximal to the exon AH1 is used while
      the expression of mRNA I, the type characteristic for muscle tissue, was not
      observed. In contrast to aldolase two isozyme types of hexokinase were detected.
      Hexokinase I as well as hexokinase II were present in thymocytes whereas
      hexokinase III was not detectable. A shift in the isozyme pattern was not
      observed during the cell cycle progression.

PMID- 7803493
TI  - Effects of extracellular bicarbonate ions and pH on volume-regulatory taurine
      efflux from rat cerebral cortical slices in vitro: evidence for separate neutral
      and anionic transport mechanisms.
AB  - Net efflux of [3H]taurine from cells in pre-loaded slices of rat cerebral cortex
      has previously been shown to occur via an anionic pathway, believed to consist of
      exchange of anionic taurine for extracellular Cl-, and operating under both
      isomotic and hypoosmotic conditions, and a calmodulin-dependent mechanism,
      activated by hypoosmotic stress: the latter may comprise conductive channels
      (Law, R.O. (1994) Biochim. Biophys. Acta 1221, 21-28). Experiments have now been
      performed to examine two inter-related problems; firstly, how anion/anion
      exchange (assuming 1:1 stochiometry) could contribute to the regulation of brain
      cell volume, and secondly, whether the hypoosmotically-activated component of
      efflux represents a second anionic transport process or loss of neutral taurine.
      The former process has been shown to be strongly dependent upon extracellular pH
      and bicarbonate concentration, being accelerated by low pH (7.0) and high (60
      mmol/l) bicarbonate, and retarded by alkalinization (pH 7.8) and low (2.5 mmol/l)
      bicarbonate. Taurine efflux is inhibited by acetazolamide, with accompanying cell
      swelling in both isoosmotic and hypoosmotic media. It is hypothesized that
      inwardly directed bicarbonate transport, in exchange for intracellular Cl-,
      operates in parallel with efflux of anionic taurine in exchange for extracellular
      Cl-, and it is the subsequent conversion of bicarbonate to CO2 and water, under
      the influence of carbonic anhydrase, that effects a volume-regulatory decrease in
      internal osmotic potential. The dependence of taurine efflux upon pH and
      bicarbonate persists in the presence of trifluoperazine (an inhibitor of
      calmodulin activation) but is abolished in hypoosmotic media by the anion
      transport inhibitor niflumic acid. Cell depolarization in high K+ has no effect
      on taurine efflux, which is envisaged as involving parallel electroneutral anion
      exchange processes (taurine/Cl- and Cl-/bicarbonate) augmented, in hypoosmotic
      media, by diffusive efflux of neutral taurine.

PMID- 7803494
TI  - On the mechanism of inactivation of muscle glycogen phosphorylase by insulin.
AB  - Glucose 6-phosphate, an allosteric inhibitor of skeletal muscle phosphorylase b,
      inhibits at physiological concentrations and conditions the phosphorylation and
      activation of the enzyme by phosphorylase b kinase. AMP inhibits the
      dephosphorylation of phosphorylase a, but is without effect on the
      phosphorylation of phosphorylase b. Glucose 6-phosphate has no effect on the
      activity of phosphorylase a and does not affect its dephosphorylation by
      phosphatases 1 or 2A. The inhibition of the phosphorylation of phosphorylase b by
      glucose 6-phosphate may explain the reported decreased phosphorylation of
      phosphorylase in muscle following insulin treatment, which elevates intracellular
      levels of glucose 6-phosphate.

PMID- 7803495
TI  - Exposure of human lymphocytes to bis-(2-chloroethyl)sulfide solubilizes truncated
      and intact core histones.
AB  - Bis-(2-chloroethyl)sulfide (BCES) is a radiomimetic, bifunctional alkylating
      agent that cross-links DNA, disrupts higher-order nuclear structure and
      selectively kills rapidly proliferating cell types. While chemically
      fractionating primary, human lymphocytes after challenge with cytotoxic doses of
      BCES, we detected a 12,900 M(r) polypeptide in 1.0 M NaCl extracts of exposed
      cells that was markedly increased compared to controls. By computer-aided image
      analysis of polyacrylamide gels, it was detected as early as 4 h following 1 mM
      BCES and increased approximately 10-fold by 24 h. Two other polypeptides of
      16,320 and 16,970 M(r) also were increased measurably at 24 h following BCES
      exposure. Altered polypeptides were found in 28 of 28 separate lymphocyte
      preparations ranging in cell density from 5 x 10(6)/ml to 6 x 10(7)/ml. They were
      not present if cells were killed with equimolar concentrations of a different
      cytotoxic agent, chlorovinyl-dichloroarsine (lewisite). Appearance of the
      polypeptides was unaffected by sulfhydryl reducing agents or pretreatment of
      cells with the protein synthesis inhibitor, cycloheximide. Micro sequencing
      resulted in a perfect match of the 12,900 M(r) polypeptide amino terminus with
      residues 19-27 of histone H2B. This corresponds to the exact site of H2B cleavage
      obtained when intact nucleosomes are treated with chymotrypsin. Sequence data
      from the other two altered polypeptides identified them as intact histone H2B and
      histone H3. Lymphocyte genomic DNA integrity also was assessed after BCES
      exposure and found to undergo extensive fragmentation typical of cellular
      necrosis. We speculate that exposure of isolated cells to BCES disrupts
      nucleosome structure by mechanism(s) that involve abnormal removal and perhaps
      proteolysis of core histones.

PMID- 7803496
TI  - Bone marrow activation by immobilized antibodies against tumor cells and
      immunocytes as a potential cancer immunotherapy.
AB  - This study was aimed at combining the limited expression pattern of the type 1
      mucin glycoproteins on tumors derived from glandular epithelia with the presence
      of integrin adhesion receptors on hematopoietic cells in order to develop an
      immunotherapy against certain types of carcinomas. To this end, monoclonal
      antibodies that recognize molecules on the surfaces of either tumor cells or
      immunocytes were immobilized on latex beads; proliferation of bone marrow cells,
      representing a source of preterminally differentiated immunocytes with potential
      antitumor activity, was measured and compared with that of mature lymphocytes in
      the presence of beads and irradiated tumor cells. It was found that only beads
      carrying antibodies against both mucins and leukocyte integrins were capable of
      inducing proliferation of bone marrow cells while none specifically stimulated
      mature lymphocytes. A proposal is put forth for the development of tumor-induced
      proliferation of bone marrow cells as a potential effective immunotherapy for
      some forms of cancer.

PMID- 7803497
TI  - Novobiocin activates the mating response in yeast through the alpha-pheromone
      receptor, Ste2p.
AB  - In a previous publication we reported the isolation of several yeast mutants
      sensitive to the coumarin drug novobiocin. Here we characterise the wild-type
      gene (NBS5), obtained by rescuing a novobiocin-sensitive nbs5 strain to natural
      novobiocin resistance. We show that nbs5 is allelic to the previously
      characterised gene sst2, conferring super-sensitivity to the mating pheromones.
      Although nbs5/sst2 cells of both mating types are super-sensitive to the opposite
      mating pheromone, only cells of mating-type a are sensitive to novobiocin. We
      show that the entire effect of the drug is mediated through Ste2p, the alpha
      pheromone receptor. Thus, novobiocin is a functional agonist of Ste2p, and may
      identify a potentially useful interaction between coumarin drugs and the family
      of G-protein-coupled receptors.

PMID- 7803498
TI  - Effect of sucrose monostearate, an emulsifier, on polyamine metabolism and
      phosphatidylinositol turnover in Ehrlich ascites tumor cells.
AB  - Sucrose esters of fatty acids have antitumor activity. We studied the effect of
      sucrose monostearate (SS), an emulsifier, on polyamine metabolism and
      phosphatidylinositol turnover in Ehrlich ascites tumor cells. The activity of
      ornithine decarboxylase (ODC) was increased in the cells by changing the medium.
      This increase in the activity was inhibited by adding sucrose stearate, but not
      sucrose or stearate to the medium. The activity of spermidine/spermine N1
      acetyltransferase (SAT), a rate-limiting enzyme of polyamine biodegradation, was
      enhanced with the addition of SS in a time- and dose-dependent manner. The
      elevation of SAT activity was completely prevented when cycloheximide was added
      to the culture simultaneously. In in vitro studies, SS at various concentrations
      up to 1 mM hardly affected the activities of ODC or SAT. The incorporation of
      [3H]inositol into both fractions of inositolphospholipid and inositol phosphates
      was inhibited by SS. These results suggest that the perturbation of polyamine
      metabolism and phosphatidylinositol turnover is involved in the mechanism of
      antitumor activity of SS in Ehrlich ascites tumor cells.

PMID- 7803499
TI  - Inhibition of protein kinase C activity and vascular smooth muscle cell growth by
      d-alpha-tocopherol.
AB  - The inhibition by d-alpha-tocopherol of protein kinase C activity has been
      studied in synchronised A7r5 rat smooth muscle cells during the cell cycle. Cell
      protein kinase C activity has been found to oscillate, with a minimum in the G0
      phase, a maximum in the late G1 phase and a new minimum in the S phase. An
      inhibition of protein kinase C activity by d-alpha-tocopherol appears to be at
      the basis of cell growth inhibition. Nevertheless, the amount of the different
      protein kinase C isoenzymes present in smooth muscle cells, measured by their
      specific antibodies, does not change during the cell cycle in both untreated and
      d-alpha-tocopherol-treated cells. The possible mechanisms of protein kinase C
      modulation during the cell cycle and of its inhibition by d-alpha-tocopherol are
      discussed.

PMID- 7803500
TI  - Plasma antiproteinase screen and neutrophil-mediated platelet activation. A major
      role played by alpha 1 antitrypsin.
AB  - Upon activation, human polymorphonuclear neutrophils (PMN) release two serine
      proteinases, cathepsin G (Cat.G) and elastase (HLE), which in turn synergize to
      activate nearby platelets. We looked for the inhibitory effect of plasma and the
      involvement of alpha 1 antichymotrypsin (alpha 1 ACT) and alpha 1 antitrypsin
      (alpha 1 AT), on this cell-to-cell cooperation. It was observed that inhibition
      by plasma of PMN-mediated platelet activation was rather correlated with an
      effect on HLE (r = 0.95) than on Cat.G (r = 0.65) enzymatic activity. Purified
      alpha 1 AT suppressed in a concentration-dependent manner HLE activity present in
      the supernatant of activated PMN. When HLE was fully blocked, alpha 1 AT started
      to inhibit Cat.G activity. By contrast and as expected, purified alpha 1 ACT
      inhibited only Cat.G activity. Using specific blocking polyclonal antibodies
      against alpha 1 AT and alpha 1 ACT, it was demonstrated that the inhibitory
      effect of plasma vs. HLE was entirely mediated by alpha 1 AT. By contrast,
      blockade of Cat.G activity was only partly due to plasma alpha 1 ACT and around
      50% was attributable to alpha 1 AT. When plasma from patients with an acute
      inflammatory state was used in place of plasma from normal subjects, the
      inhibitory effect was more pronounced, while plasma depleted in alpha 1 AT and
      alpha 1 ACT was less effective. These data indicate a predominant role of alpha 1
      AT in the inhibition by plasma of the PMN-mediated platelet activation.

PMID- 7803501
TI  - Further evidence of different lactoferrin and transferrin binding sites on human
      HT29-D4 cells. Effects of lysozyme, fucose and cathepsin G. Comparison with
      transferrin.
AB  - We have defined by using competition experiments the nature of specific
      lactoferrin binding sites, probably responsible for the previously observed
      stimulatory growth effect of the iron binding protein on HT29-D4 cells. Lysozyme,
      albumin and fucose do not affect lactoferrin binding showing that the binding of
      the protein is mediated neither by electrostatic forces nor by fucose. Iron-free
      and iron-loaded protein produce similar effects, demonstrating that the metal is
      not involved in the protein recognition. Similar results are observed for
      transferrin. A specific binding inhibition of lactoferrin by cathepsin G, a
      leukocyte proteinase, is observed, suggesting the existence of a common receptor
      for lactoferrin and cathepsin G on HT29-D4 cells. These results and the fact that
      tumor tissues are more often infiltrated by inflammatory cells such as
      polymorphonuclear leukocytes could evoke an unexpected role for leukocytes,
      possibly mediated in part by these two proteins, on the proliferative cancer
      effect.

PMID- 7803502
TI  - Endocytosis does not necessarily augment the cytotoxicity of adriamycin
      encapsulated in immunoliposomes.
AB  - We studied the relationship between endocytosis and cytoxicity of adriamycin
      (ADM) encapsulated in antibody-coated liposomes (immunoliposomes, IL) which are
      called chemoimmunoliposomes (CIL), by using several human cancer cell lines. IL
      coated with a monoclonal antibody, HBJ127 (IgG), which recognizes human gp125
      antigen, specifically bound to gp125-positive target cancer cell lines, KU-1,
      T24, MKN-7, SKBr-3 and LS174T. Flow cytometric analysis using IL encapsulating
      carboxyfluorescein (CF) revealed that efficiencies of endocytosis varied among
      different cancer cells. The rate of IL internalization was in the order KU-1 >
      T24 > MKN-7 > SKBr-3 > LS174T. In 1 h incubation at 37 degrees C, all the four
      cell lines other than LS174T internalized about 60% of IL which were bound on
      their cell surfaces. KU-1, T24 and MKN-7, but not SKBr-3, significantly processed
      IL in endosome or lysosome. On the contrary, 80% of CIL bound to LS174T remained
      on the cell surface even after 2 h incubation. Furthermore, we evaluated the
      cytotoxic activities of CIL against the same panels of cancer cells. CIL
      inhibited the growth of all cancer cells tested in antibody-dependent manner,
      but, contrary to our expectation, KU-1 and T24 cells, which showed significant
      endocytosis activity, required a 7-14-fold higher amount of ADM binding than
      LS174T cells with low endocytosis activity for 50% cell growth inhibition. The
      difference of sensitivity to free ADM was only within 2.3-fold among those cancer
      cells. These results showing that liposomal ADM endocytosed is less effective
      than that remaining on the cell surface suggest that endocytosis is not
      necessarily required for cytotoxicity of CIL.

PMID- 7803503
TI  - Autoregulation of endothelin-1 secretion by cultured human keratinocytes via the
      endothelin B receptor.
AB  - We investigated endothelin-1 (ET-1) receptor expression on normal human
      keratinocytes (HK). We show that HK express the ETB receptor isoform and respond
      to ET-1 with a 2.7-fold increase in intracellular free calcium. HK did not
      respond to ET-1 with increased proliferation; however, 30 nM ET-1 caused a 51.7%
      decrease in ET-1 accumulation in HK-conditioned medium. We propose that HK ET-1
      receptors function in autocrine regulation of ET-1 secretion.

PMID- 7803504
TI  - Inverse relationship of cotranslational translocation with the hydrophobic moment
      of the bovine preproparathyroid hormone signal sequence.
AB  - To investigate the dependence of transmembrane translocation on the hydrophobic
      moment of the hydrophobic core of the preproparathyroid hormone signal sequence,
      amino acids were switched to maximize or minimize the hydrophobic moment without
      changing the length or overall hydrophobicity of the core. As assayed in an in
      vitro translation system with microsomal membranes, the efficiency of
      translocation of these mutants was inversely related to the hydrophobic moment,
      indicating the hydrophobic moment or a related property may contribute to
      translocational activity.

PMID- 7803505
TI  - Nucleotide and deduced amino acid sequence of a putative higher molecular weight
      precursor for catalase in sunflower cotyledons.
AB  - A cDNA from a sunflower (Helianthus annuus L.) library encoded a 56.8 kDa
      catalase peptide. N-terminal sequence comparisons to peroxisomal higher molecular
      weight precursors revealed conserved amino acid motifs around the (putative)
      cleavage sites. These findings suggest that the 55 kDa catalase in sunflower
      cotyledons is synthesized at a higher molecular weight.

PMID- 7803506
TI  - A kinase anchor proteins and the intracellular targeting of signals carried by
      cyclic AMP.

PMID- 7803507
TI  - Calpain-induced down-regulation of protein kinase C inhibits dense-granule
      secretion in human platelets. Inhibition of platelet aggregation or calpain
      activity preserves protein kinase C and restores full secretion.
AB  - The relationship between platelet aggregation, calpain activation, PKC activities
      and the secretory response have been examined in PMA-and ionomycin-stimulated
      platelets. Co-addition of PMA and ionomycin resulted in a maximal synergistic
      secretion of [14C]5-hydroxytryptamine ([14C]5-HT) from platelet dense granules.
      However, prior addition of PMA for 5 or 10 min resulted in a reduction of this
      secretory response. Inclusion of either RGDS (to inhibit platelet aggregation) or
      E64-d (to inhibit calpain activity) resulted in full restoration of the secretory
      response. In experiments to determine the activity status of PKC, PMA was found
      to induce a loss in cytosolic and total PKC activity without an increase in
      membrane-associated activities during this time period. Inhibition of either
      platelet aggregation or calpain activity resulted in preservation of total and
      cytosolic activities with a measurable increase in membrane translocated
      activity. PMA-induced phosphorylation of a number of PKC substrates was measured
      in 32P-labelled platelets. PMA induced potent phosphorylation of the 45 and 20
      kDa species and also proteins of the molecular masses 66, 80, 97 and 119 kDa.
      Phosphorylation was maximal at either 1 or 2 min after which dephosphorylation
      occurred. Inclusion of either RGDS or E64-d resulted in a reduction of the
      dephosphorylation rates, and sustained phosphorylation of the 66, 80, 97 and 119
      kDa proteins. These studies suggest that the activity status of PKC is an
      important factor in the level of secretion obtained and that platelet aggregation
      is involved in calpain-initiated down-regulation of PKC.

PMID- 7803508
TI  - The mitogenic action of recombinant basic FGF in Swiss 3T3 cells is independent
      of early diradylglycerol production and downregulatable protein kinase C
      activity.
AB  - In this study we have investigated the requirement for phosphoinositide
      metabolism, diradylglycerol (DG) production and protein kinase C (PKC) activation
      in recombinant basic fibroblast growth factor (rbFGF)-mediated reinitiation of
      DNA synthesis in Swiss 3T3 cells. We have assessed the involvement of PKC
      activation in rbFGF-induced DNA synthesis by two approaches; enzymic inhibition
      by H7 and down-regulation by prolonged phorbol-ester treatment. In both
      conditions we observed that rbFGF was able to sustain a significant component of
      its mitogenic response, therefore denying an exclusive role for the activation of
      downregulatable and H7-sensitive PKC isoforms in rbFGF-induced reinitiation of
      DNA synthesis. Moreover, we have found no evidence for diacylglycerol
      accumulation in response to rbFGF by 3T3 cells. In previous studies, we observed
      that rbFGF caused a moderate and slow accumulation of total inositol phosphates.
      This effect was significant only after a 60 min incubation. It is our contention
      that rbFGF, in our culture system, does not exert a direct effect on
      phosphoinositide metabolism.

PMID- 7803509
TI  - Inhibition of the T-cell receptor-mediated signal transduction by microinjection
      of anti-Lck monoclonal antibody into T-cells.
AB  - Engagement of T-cell receptor (TcR)/CD3 complexes on T-cells rapidly provokes
      tyrosine phosphorylation of cellular proteins, which is thought to be an
      essential step to the following events of T-cell activation. p56lck, a member of
      src-related, non-receptor type protein tyrosine kinases, is expressed
      predominantly in lymphocytes. Accumulating data suggest that p56lck is one of the
      kinases responsible for TcR-mediated protein tyrosine phosphorylation. To
      investigate the role of p56lck in TcR-signaling in detail, we injected anti-Lck
      monoclonal antibody (mAb), MOL171 or MOL294, both specifically suppress Lck
      kinase activity in vitro, into Jurkat T-cells by the erythrocyte-ghost procedure
      in order to block the activity of p56lck. In Jurkat cells injected with anti-Lck
      mAb, intracellular Ca2+ mobilization induced by TcR-stimulation was markedly
      reduced in comparison with control mouse IgG-injected samples. This block of Ca2+
      influx seems to be specific for TcR-signaling because anti-Lck mAb-injection did
      not cause significant suppression of phytohaemagglutinin-induced Ca2+ increase.
      Furthermore, injection of anti-Lck mAb inhibited TcR-mediated protein tyrosine
      phosphorylation of 100 kDa protein and phospholipase C gamma 1. These results
      confirm that p56lck is an indispensable element of TcR-signaling and p100 and
      phospholipase C gamma 1 are strongly presumed to be candidates for substrates for
      p56lck.

PMID- 7803510
TI  - Characterization of integrin expression and regulation on SW-480 human colon
      adenocarcinoma cells and the effect of rhodostomin on basal and upregulated tumor
      cell adhesion.
AB  - Integrins are a superfamily of cell surface glycoproteins that mediate cell
      extracellular matrix (ECM) and cell-cell adhesion. Immunofluorescence microscopy
      and flow cytometric analysis using anti-integrin mAbs as the primary binding
      ligands demonstrated that the platelet integrin receptor alpha IIb beta 3, as
      well as alpha v beta 3, alpha 5 beta 1 and alpha 6 beta 1, are present on the
      surface of SW-480 human colon adenocarcinoma cells. Monoclonal antibodies (mAbs)
      against alpha IIb beta 3 and alpha 5 beta 1 inhibited unstimulated basal adhesion
      to fibronectin by approximately 30% and 40%, respectively. The surface
      immunoreactivity of tumor cells for alpha IIb beta 3 was enhanced by pretreatment
      (5 min) with a phorbol ester (12-O-tetradecanoylphorbol-13-acetate (TPA)) or a
      lipoxygenase metabolite of arachidonic acid, 12-hydroxyeicosatetraenoic acid (12
      HETE) in a dose- and time-dependent manner. SW-480 cells possess a large
      intracellular pool of alpha IIb beta 3, from which the receptor complex
      translocates to the cell surface following pretreatment with TPA or 12(S)-HETE.
      This pretreatment enhances adhesion to fibronectin, which is mediated exclusively
      by alpha IIb beta 3 integrins. Staurosporine was found to block alpha IIb beta 3
      up-regulation and enhanced-adhesion. TPA and 12(S)-HETE also facilitated the
      redistribution of alpha IIb beta 3 during the enhanced-spreading process.
      Rhodostomin, an Arg-Gly-Asp- (RGD) containing antiplatelet snake venom peptide,
      was about 400-times more potent than RGDS at inhibiting control, TPA- or 12(S)
      HETE-enhanced adhesion of SW-480 cells to fibronectin. The binding of mAbs
      against alpha IIb beta 3, alpha v beta 3 and alpha 5 beta 1 was inhibited by
      pretreatment with rhodostomin, suggesting that rhodostomin binds via its RGD
      sequence to multiple integrin receptors (i.e., alpha IIb beta 3, alpha v beta 3,
      alpha 5 beta 1) expressed on the SW-480 cell surface, inhibiting cell adhesion to
      ECM.

PMID- 7803512
TI  - Rat preadipocyte adenylyl cyclase: influence of fat localization and androgenic
      status.
AB  - The influence of androgenic status on basal and stimulated cAMP production,
      adenylyl cyclase activities and immunoblot quantified GS alpha and Gi alpha 2
      subunits of the adenylyl cyclase regulatory proteins were compared in confluent
      preadipocytes from subcutaneous (SC) and deep-intraabdominal (epididymal) fat
      deposits. Maximal cAMP response to isoproterenol was lower in SC than in
      epididymal preadipocytes. After castration, this site-specific difference was
      suppressed. cAMP response to 2-chloroadenosine, which was identical in the two
      types of preadipocytes, was decreased by castration in epididymal cells but not
      in SC cells. The catalytic activity of adenylyl cyclase and its maximal response
      to GTP were higher in epididymal than in SC preadipocytes. This response to GTP
      was decreased by castration in epididymal preadipocytes while it remained
      unchanged in SC preadipocytes. The catalytic activity of adenylyl cyclase was
      unchanged by androgenic status whatever the cell localization. Levels of GS alpha
      quantified by immunoblotting were not modified whatever the androgenic status and
      cell origin. Levels of Gi alpha 2 were not affected by the androgenic status as
      well, but were lower in SC than in epididymal cells. This study shows that
      components of the adenylyl cyclase system in preadipocytes are differently
      regulated by the androgenic status depending on the anatomical origin of the
      cells.

PMID- 7803511
TI  - Ins 1,4,5-P3 and Ca2+ signaling in quiescent neonatal cardiac myocytes.
AB  - Activation of alpha 1-adrenergic receptors in neonatal cardiac myocytes results
      in changes in contractile activity and the induction of hypertrophic growth. The
      biochemical mechanisms responsible for these diverse effects are not yet
      established, but presumably involve the associated alpha 1-adrenergic stimulation
      of phosphatidylinositol (PI) hydrolysis, with concomitant generation of Ins 1,4,5
      P3 and diacylglycerol. This study examined whether alpha 1-adrenergic generation
      of Ins 1,4,5-P3 in intact, quiescent, neonatal cardiac myocytes resulted in a
      Ca2+ signal. Stimulation of myocytes with norepinephrine in the presence of
      propranolol caused accumulation of inositol mono-, bis and trisphosphates.
      However, alpha 1-adrenergic stimulation did not alter cytosolic free Ca2+ levels
      in 85% of the myocytes examined. Direct generation of Ins 1,4,5-P3, by photolysis
      of microinjected caged Ins 1,4,5-P3, was also unable to alter cytosolic free Ca2+
      levels, despite the presence of Ins 1,4,5-P3 receptors. Taken together, these
      data indicated that alpha 1-adrenergic stimulation did not initiate Ca2+
      signaling because Ins 1,4,5-P3-induced Ca2+ mobilization was not operative in
      quiescent neonatal cardiac myocytes. Normal excitation-contraction Ca2+ handling
      mechanisms were present in these cells, as illustrated by depolarization- and
      caffeine-induced Ca2+ transients. Analysis of these same myocytes following 48 h
      in the presence of norepinephrine and propranolol showed a 40% increase in the
      ratio of protein to DNA and a 350% increase in release of atrial naturietic
      factor, compared to control cells, indicating the normal operation of alpha 1
      adrenergic-induced hypertrophic growth. Therefore, the assumption that Ca(2+)
      dependent processes will be activated by receptor signaling pathways coupled to
      enhanced phosphatidylinositol turnover in cardiac cells must be avoided. In
      addition, the data presented in this study clearly indicated that an increase in
      cytosolic free Ca2+ was not necessary for the induction of alpha 1-adrenergic
      mediated cardiac hypertrophy.

PMID- 7803513
TI  - Characterization of a protein which binds phosphatidylinositol 3,4,5
      trisphosphate and 4,5-bisphosphate.
AB  - Protein(s) which bind polyphosphatidylinositol phosphates (PI 3,4,5-P3 and PI 4,5
      P2) were identified in the wheat-germ agglutinin bound fraction of cells and
      tissues. The binding of this protein(s) to the phospholipid could be demonstrated
      in two ways, either by a shift in the migration of the lipid by size exclusion
      column chromatography or directly by binding to the protein after capture on
      wheat-germ agglutinin-coupled beads. Of the rat tissues tested (muscle, spleen,
      brain, heart, kidney and liver), the activity was highest in liver. The
      protein(s) was purified more than 5000-fold by sequential chromatography on
      columns of wheat-germ agglutinin, phosphocellulose, Blue-Sepharose, Mono Q and
      Superose 6. The peak of activity appeared to have a molecular weight on this
      latter column of approx. 240,000. The protein(s) bound PI 3,4,5-P3, PI 3,4-P2,
      and PI 3-P in the ratio of 4:2:1. The binding of 3-phosphorylated PI phosphates
      to the protein(s) was not significantly inhibited by 36 micrograms/ml of either
      phosphatidylinositol or phosphatidylcholine, but was inhibited 10% and 65% by 36
      micrograms/ml of PI 4-P and PI 4,5-P2, respectively. Since these results
      suggested that the binding protein(s) could also bind PI 4,5-P2, binding of this
      lipid was directly tested and found to be comparable to that of PI 3,4,5-P3.
      These results suggest that this protein(s) could be involved in the signaling
      mechanism elicited by these polyphosphoinositides.

PMID- 7803515
TI  - Protein kinase C expression and translocation in dispersed chief cells from
      guinea-pig stomach.
AB  - The protein kinase C (PKC) family of enzymes is comprised of at least nine
      isoforms that vary with respect to co-factor dependence, cellular distribution
      and substrate specificity. Using specific antibodies for alpha, beta, gamma,
      delta, epsilon, zeta and eta PKC isoforms, and Western blot analysis, we found
      that alpha and zeta PKC are expressed in gastric chief cells. We then used these
      methods to examine the effects of carbamylcholine, a cholinergic agonist that
      increases cellular calcium and diacylglycerol concentrations, and PMA, a phorbol
      ester that activates PKC, on the subcellular distribution of these isoforms.
      Carbamylcholine and PMA caused an increase in membrane-associated alpha PKC, but
      did not alter the subcellular distribution of zeta PKC. Comparison of the dose
      response curves for carbamylcholine-induced pepsinogen secretion and alpha PKC
      membrane-association indicates that PKC translocation is not required for
      carbamylcholine-induced secretion. Nevertheless, maximal carbachol-induced
      secretion occurs at concentrations that also cause translocation of the alpha
      isoform. Whereas treatment of chief cells with PMA (300 nM) for 4 h down
      regulated levels of alpha PKC by 61%, there was no change in the levels of zeta
      PKC. Separation of the two PKC isoforms in chief cell lysates by DEAE-column
      chromatography revealed that kinase activity in fractions containing the alpha
      isoform was increased more than 3-fold by calcium and lipids. In contrast, kinase
      activity in fractions containing the zeta isoform was not altered. In gastric
      chief cells, translocation and activation of alpha PKC occurs in response to
      agonist-induced increases in calcium and diacylglycerol. Zeta PKC may be involved
      in the regulation of basal pepsinogen secretion.

PMID- 7803514
TI  - Levels and localization of group II phospholipase A2 and annexin I in interleukin
      and dexamethasone-treated rat mesangial cells: evidence against annexin
      mediation of the dexamethasone-induced inhibition of group II phospholipases A2.
AB  - The mechanism by which glucocorticosteroids inhibit the synthesis and secretion
      of pro-inflammatory arachidonate metabolites is still controversial. Initially it
      was postulated that glucocorticoids can induce the formation of PLA2 inhibitory
      proteins termed annexins. We have previously shown that the cytokine-induced 14
      kDa PLA2 activity and the synthesis of prostaglandin E2 in rat mesangial cells is
      dose-dependently blocked by pretreatment of the cells with dexamethasone
      (Schalkwijk et al. (1991) Biochem. Biophys. Res. Commun. 180, 46-52).
      Concurrently, the synthesis of 14 kDa group II PLA2 is suppressed. The regulation
      of PLA2 activity is complex and may well involve superimposable mechanisms. Thus,
      although the decrease in PLA2 protein levels could in itself explain the
      dexamethasone-induced decrease in PLA2 activity, a contribution of the
      glucocorticoid-induced anti-phospholipase A2 protein annexin cannot be ruled out
      a priori. To investigate this possibility we analyzed the level of annexin I by
      Western blotting and immunostaining in mesangial cells treated with interleukin-1
      beta and/or dexamethasone. Under conditions where 14 kDa group II PLA2 activity
      and protein levels were dramatically affected by interleukin-1 and dexamethasone,
      the level of annexin I in the cells remained constant. Dexamethasone also did not
      induce the secretion of annexin I. In addition, no evidence for dexamethasone
      induced translocation of annexin I from the cytosol to membranes, thereby
      possibly sequestering the substrates for PLA2, was obtained. Immunofluorescence
      studies localized the cytokine-induced PLA2 to the Golgi area and punctate
      structures in the cytoplasm. We have also studied the subcellular localization of
      annexin I in rat mesangial cells using confocal microscopy. These studies located
      annexin I mainly in the cytoplasma and the nucleus. We conclude from these
      experiments that the dexamethasone-induced inhibition of 14 kDa group II PLA2 in
      rat mesangial cells is not mediated by annexin I and is solely due to the
      suppression of PLA2 gene expression.

PMID- 7803516
TI  - Role of sialic acid residues in the in vitro superactivity of human
      choriogonadotropin (hCG) in rat Leydig cells.
AB  - The binding activity (B) of porcine Luteinizing Hormone (pLH) to rat LH receptor
      as well as its stimulating activity (S) of testosterone secretion by rat Leydig
      cells in vitro are similar to those of the homologous hormone rat LH (S/B = 1).
      By contrast, the human Chorionic Gonadotropin (CG) and hLH exhibit stimulating
      activities relative to rat LH that are considerably higher than their relative
      binding activities (S/B > 100) indicating that they have an abnormally high
      transducing efficiency (superactivity) after receptor binding. The heterologous
      hybrid alpha pLH x beta hCG is as superactive as native hCG and recombined alpha
      hCG x beta hCG whereas alpha hCG x beta pLH exhibits no superactivity, like
      native pLH and alpha pLH x beta pLH demonstrating that hCG superactivity is due
      to its beta-subunit. The removal of sialic acid residues with neuraminidase
      dramatically diminished hCG stimulating activity without impairing its receptor
      binding activity but the S/B ratio for asialo-hCG never reached values lower than
      1. Similar treatments had no effect on the S/B ratios of non-superactive
      gonadotropins, pLH and equine CG. Sialic acid residues in the Asn beta 30
      carbohydrate chains of hLH and hCG appear to be responsible for their
      superactivity in the in vitro stimulation of testosterone secretion by rat Leydig
      cells.

PMID- 7803518
TI  - U-73122, a phospholipase C antagonist, inhibits effects of endothelin-1 and
      parathyroid hormone on signal transduction in UMR-106 osteoblastic cells.
AB  - Endothelin-1 (ET-1) and parathyroid hormone (PTH) increase calcium transients in
      rodent osteoblastic cells. To investigate the role of phospholipase C (PLC) in
      these hormone-stimulated calcium signals, the effects of U-73122 (1-[6-[[17 beta
      3-methoxyestra-1,3,5(10)- trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione), a
      reported PLC inhibitor, and its inactive analog, U-73343 (1-[6[[17 beta-3
      methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]- 1H-pyrrolidine-2,5-dione), were
      determined. Intracellular calcium transients were measured in UMR-106 cells with
      the fluorescent indicator fluo-3. In normal calcium containing medium, prior
      exposure (3 min) to U-73122 inhibited ET-1 and PTH stimulated calcium transients
      in a dose-dependent (0.2-10 microM) manner with an IC50 of 1.5-1.8 microM. A
      concentration of 6-8 microM was required for complete inhibition of responses to
      100 nM ET-1 or PTH. U-73343 elicited no effects over this concentration range. In
      cells in which external calcium was reduced to less than 1 microM by the addition
      of EGTA, ET-1 signals were completely inhibited by 4-6 microM U-73122 and the
      IC50 was 0.8 microM. In the low external calcium medium, the PTH response was
      abolished by 2 microM U-73122 (IC50 = 0.5 microM). U-73122, 8 microM,
      significantly (P < 0.01) inhibited the effect of ET-1 on inositol trisphosphate
      production at 3 min whereas U-73343 did not. Pertussis toxin (100 ng/ml) likewise
      significantly inhibited the effect of ET-1 on phosphoinositol turnover as well as
      on intracellular calcium concentration. In conclusion, the results support the
      hypothesis that PLC plays a role in the calcium transients elicited by ET-1 and
      PTH, and that ET-1 transmits its signal in part via a pertussis toxin sensitive G
      protein coupled receptor. Furthermore they suggest that U-73122 is useful for
      investigating PLC-mediated process in osteoblastic cells.

PMID- 7803517
TI  - Cyclic AMP-plus ATP-dependent modulation of the NADH oxidase activity of porcine
      liver plasma membranes.
AB  - Plasma membranes of porcine liver, highly purified by aqueous two-phase
      partition, oxidized NADH in the absence of added external acceptors. The
      oxidation was resistant to cyanide and responded to nanomolar concentrations of
      ATP alone or ATP in the presence of cyclic AMP. Both the Km for NADH and the long
      term activity of the oxidase were affected. Upon incubation at 37 degrees C with
      cyclic AMP (0.1-10 nM) and ATP (1-100 nM), the NADH oxidase activity was
      inhibited. The inhibition was complex and due to an approx. 5-fold increase in
      the Km for NADH compared to the NADH oxidase of membranes incubated in the
      absence of cyclic AMP + ATP. The response to cAMP + ATP was rapid and occurred
      within seconds of ATP addition. The response was inhibited by the selective
      inhibitor of cyclic AMP-dependent protein kinase, H-89. Neither cyclic AMP alone
      nor ATP alone at nanomolar concentrations elicited a rapid response. However, 10
      nM ATP alone did result in similar alteration of Km and Vmax as did ATP + 0.1 nM
      cyclic AMP. The response to ATP alone or in preparations depleted of cyclic AMP
      required higher ATP concentrations than with cAMP present or occurred more slowly
      with a lag of 1-2 min. The NADH oxidase activity of porcine plasma membranes
      after cyclic AMP + ATP treatment retained high activity with storage at 4 degrees
      C, whereas that of unincubated or sham-incubated plasma membranes was reduced
      with time of storage at 4 degrees C. In some but not all instances, NADH oxidase
      activity inactivated by incubation with NADH at 37 degrees C or after storage at
      4 degrees C could be reactivated by incubation with cyclic AMP plus ATP. As with
      the alteration in Km, cyclic AMP alone was without effect and ATP alone was much
      less effective than the combination. The results demonstrate ATP-dependent
      modulation of the NADH oxidase activity of isolated plasma membranes at
      physiological concentrations of ATP. This modulation may have functional
      significance in mediating the hormone and growth factor responsiveness of the
      plasma membrane NADH oxidase activity.

PMID- 7803519
TI  - The effect of calcium on mitochondrial contact sites: a study on isolated rat
      hearts.
AB  - Mitochondrial contact sites are dynamic structures created by fusion of the inner
      and outer mitochondrial membranes. Stimulation of the metabolism results in an
      increase of the number of contact sites. Functionally, it is shown that
      mitochondrial creatine kinase (Mi-CK) is active in contact sites and therefore,
      Mi-CK cytochemistry was performed (using a tetrazolium salt) to improve the
      visibility of the contact sites. As calcium is involved as an intracellular
      messenger of hormonal stimulation, the effect of increasing extracellular calcium
      concentrations on the number of contact sites was investigated. Therefore,
      isolated rat hearts were perfused with Krebs-Henseleit buffers differing in their
      calcium content. During the perfusions the heart function was evaluated and at
      the end of each experiment, the hearts were processed for Mi CK cytochemistry and
      the number of contact sites was expressed as the ratio of surface densities
      contact sites to mitochondrial membranes (Ss). At 2.2 mM calcium perfusion, the
      physiological parameters and the Ss reached a maximum. This was in contrast to
      the 0.6 and the 3.6 mM of calcium perfusions whereby both the physiological
      values and the Ss were decreased. Treatment with noradrenaline in vivo, as was
      done in previous studies or perfusion with 2.2 mM of calcium ends up with similar
      values for Ss. From these results, it could be suggested that there might be a
      link between calcium, heart function and the formation of Mi CK active contact
      sites.

PMID- 7803520
TI  - Progesterone-induced phospholipid N-methylation and sphingomyelin synthesis in
      the amphibian oocyte plasma membrane: a second source of the 1,2-diacylglycerol
      second messenger associated with the G2/M transition.
AB  - The effects of progesterone and GTP gamma S on phospholipid N-methylation and
      sphingomyelin synthesis were studied in plasma-vitelline membranes isolated from
      amphibian (Rana pipiens) oocytes. Plasma-vitelline membranes were preincubated
      with S-adenosyl-L-[methyl-3H]methionine for 2 min at 20 degrees C and total
      phospholipids extracted at 0, 15, 30 and 60 s after addition of progesterone
      and/or GTP gamma S. Progesterone levels (3 microM) that induce meiosis in the
      intact oocyte stimulated [3H-methyl]incorporation into
      phosphatidylmonomethylethanolamine (PME) 9-10-fold over the first 60 s, with
      smaller increases in phosphatidyldimethylethanolamine (PDE) and
      phosphatidylcholine (PC). [methyl-3H] labeling of sphingomyelin (SM) rises after
      30 s, approaching that of [methyl-3H]PME by 60 s. 17 beta-Estradiol, a noninducer
      of meiosis, was inactive. When oocytes were prelabeled with [3H]palmitic acid, it
      was found that a fall in [3H]ceramide coincides with the transient increase in
      [3H]SM, indicating that the end product of N-methylation (PC) undergoes a
      transfer reaction with ceramide to form SM and 1,2-DG. GTP gamma S levels
      previously reported to stimulate PC-specific phospholipase C activity in oocyte
      plasma membranes (5 microM) also stimulated both [methyl-3H]PME and [methyl-3H]SM
      formation. An inhibitor of phospholipid N-methylation, 2-(methyl-amino)ethanol,
      blocked stimulation of [methyl-3H]SM synthesis by both progesterone and GTP gamma
      S as well as induction of meiosis by progesterone. Progesterone thus acts at the
      oocyte plasma membrane to stimulate PE N-methyltransferase and SM synthase. The
      finding that GTP gamma S mimics progesterone suggests that N-methyltransferase is
      mediated by G-protein(s). The transient increase in 1,2-DG which we had
      previously reported to occur within 1-2 min following progesterone stimulation of
      the Rana oocyte appears to arise from PC by two different pathways: SM synthesis
      and hydrolysis of PC by phospholipase C.

PMID- 7803521
TI  - Inhibitory effect of curcumin on epidermal growth factor receptor kinase activity
      in A431 cells.
AB  - We explored the mechanism of antigrowth action of Curcumin by investigating its
      effect on epidermal growth factor (EGF) receptor intrinsic kinase activity in the
      human epidermoid carcinoma A431 cells. The short-term treatment of cells with
      Curcumin inhibited EGF receptor intrinsic kinase activity up to 90% in a dose-
      and time-dependent manner, and also inhibited EGF-induced tyrosine
      phosphorylation of EGF receptors. The observed early effects of Curcumin were
      mediated via a cellular mechanism(s), and preceded the period when inhibition of
      cell growth occurred.

PMID- 7803522
TI  - Cloning and expression of a cDNA for rat prostacyclin receptor.
AB  - A cDNA clone for rat prostacyclin receptor was isolated. The cDNA encodes a
      protein of 416 amino acid residues (M(r) 44,662) with putative seven
      transmembrane domains, and belongs to the G protein-coupled receptor superfamily.
      Specific binding of [3H]iloprost was found in membrane of COS-7 cells transfected
      with the cDNA (Kd = 1.3 nM) and was displaced with unlabeled prostaglandins in
      the order of iloprost = cicaprost > PGE1 > STA2 = PGE2 = PGD2 > PGF2 alpha.
      Northern blot analysis demonstrated that rat prostacyclin receptor mRNA is
      expressed in the lung, spleen, heart, pancreas, thymus, stomach and aorta.

PMID- 7803523
TI  - Clinical efficacy of gamma-hydroxybutyric acid in treatment of opiate withdrawal.
AB  - This paper describes the role of gamma-hydroxybutyric acid (GHB) in the treatment
      of opiate withdrawal syndrome. In the two patients described, after having
      abruptly withdrawn from long-term methadone treatment, GHB was orally
      administered (each dose given every 4-6 h) for 8-9 days. The GHB showed both a
      high efficacy (some mild and transient symptoms attributable to opiate withdrawal
      were observed, but only in the first days of therapy) and a good tolerability (no
      clinical phenomena interpreted as GHB side effects were found). These results
      could be of interest in improving the pharmacological treatment of drug
      addiction.

PMID- 7803525
TI  - Uprooting and late-life psychosis.
AB  - Biographical information was collected on 60 patients suffering from late-onset
      (> 50 years) paranoid psychosis (with and without hallucinations), 38 by chart
      review and 22 by personal examination. Of the patients 28 (47%) had been war
      refugees expelled from the eastern territories that Germany lost after World War
      II. This is more than twice the rate of the Bavarian general population. The
      onset of paranoid symptoms was usually 3 or 4 decades after immigration into
      western Germany. Among patients with Alzheimer's disease and with endogenous
      depression the proportion of former war refugees was significantly lower (22%
      each). The possible relevance of early uprooting and expulsion to the development
      of late-life paranoid psychosis is examined.

PMID- 7803526
TI  - Follow-up and family study of postpartum psychoses. Part II: Early versus late
      onset postpartum psychoses.
AB  - Patients suffering from a severe psychiatric postpartum disorder (n = 119) were
      classified according to early onset (EO) of symptoms, i.e. onset within 2 weeks
      postpartum, versus late onset (LO) in the 3-month period following delivery. The
      patients were admitted for the first time in their life to a psychiatric
      hospital. The EO cases more often had a manic syndrome, the symptomatology of
      cycloid psychoses, signs of confusion and an abrupt onset of illness. They were
      also younger at the index delivery and at the first episode of illness. No
      important difference in the distribution of diagnoses considering the long-term
      course was found in the two groups. The global psychopathological outcome was
      also similar. There is no definite evidence that different diseases are provoked
      in the early and later postpartum period.

PMID- 7803524
TI  - Diminished cerebral metabolic response to motor stimulation in schizophrenics: a
      PET study.
AB  - Positron emission tomography (PET) and the deoxyglucose method were used to
      measure cerebral metabolism in 14 normals and 13 schizophrenics at rest and
      during performance of simple and complex finger-movement sequences. The normals,
      but not the schizophrenics, showed significant metabolic activation in mesial
      frontal and contralateral sensorimotor and premotor regions during the complex
      movement. The relative metabolism of schizophrenics was significantly lower than
      normal in frontal regions and higher than normal in thalamus and basal ganglia
      under all scanning conditions. The results suggest that schizophrenics may have a
      brain dysfunction which limits their capacity to produce a focal metabolic
      response to stimulation in several functionally distinct brain regions.

PMID- 7803527
TI  - Follow-up and family study of postpartum psychoses. Part III: Characteristics of
      psychoses occurring exclusively in relation to childbirth.
AB  - As part of a follow-up and family study of postpartum psychoses, this episode of
      illness being the first leading to psychiatric hospitalisation, patients with
      puerperal episodes (PE) and nonpuerperal episodes (NPE) of illness in the long
      term course (n = 79) were compared to patients with PE only (n = 40). Few
      differences were found. Relatives of patients with PE only had a lower morbidity
      risk for functional psychoses than relatives of patients with PE and NPE. A
      favourable course of illness in the presence of a low genetic predisposition may
      be expected, according to the diathesis-stress model of functional psychoses.

PMID- 7803528
TI  - Follow-up and family study of postpartum psychoses. Part IV: Schizophreniform
      psychoses and brief reactive psychoses: lack of nosological relation to
      schizophrenia.
AB  - Among 30 women suffering from a postpartum psychosis without affective syndrome,
      and for whom this episode of illness was the first leading to psychiatric
      hospitalisation, 19 fulfilled in the long-term course the DSM-III-R criteria for
      schizophreniform psychosis (SCHF) or brief reactive psychosis (BRP), and 11
      fulfilled the criteria for schizophrenia (SCH). The two groups were compared in
      order to investigate their nosological relation. Patients with SCHF or BRP more
      often had the symptomatology of cycloid psychoses and signs of confusion, the
      onset of illness was more frequently abrupt and the age at the index delivery
      tended to be lower (p < 0.07) than in patients with SCH. No case of SCHF or BRP
      was observed at the index episode that later developed into SCH. These findings,
      together with the different liability to puerperal decompensations, suggest that
      SCHF and BRP beginning in the postpartum period are nosologically distinct from
      SCH.

PMID- 7803529
TI  - The Zurich Study: XXIII. Epidemiology of headache syndromes in the Zurich cohort
      study of young adults.
AB  - This study examines the 1 year prevalence rates of headache syndromes in an
      epidemiologic cohort study of young adults ages 29-30 in Zurich, Switzerland. The
      1 year prevalence rates of headache subtypes were 3.3% for migraine with aura and
      21.3% of migraine without aura as defined by the International Headache Society
      (IHS) criteria. The demographic distribution, clinical features, sequelae, and
      treatment patterns of subjects with specific headache subtypes are described. The
      rates of migraine are compared to those of other community samples that have
      employed the IHS criteria for headache subtypes. Subjects with migraine reported
      pervasive impairment in nearly every life role including occupation, leisure, and
      social relationships. Despite the substantial degree of impairment in
      occupational and social functioning that was associated with migraine, an
      extremely low proportion of subjects had received professional treatment for
      headache. These results suggest that a concerted effort should be directed
      towards education regarding the classification of headache and the availability
      of efficacious treatment for migraine.

PMID- 7803532
TI  - Sarcomas.

PMID- 7803530
TI  - Smooth-pursuit eye movement dysfunction in schizophrenia: the role of attention
      and general psychomotor dysfunctions.
AB  - Smooth-pursuit eye-tracking performance was examined in 100 schizophrenic
      patients and various control groups under both attention-enhancing and attention
      distracting conditions. The level of attentional demand was varied by introducing
      a secondary reaction time task that directed attention either toward or away from
      the visual-tracking target. Distraction from the target led to a significant
      deterioration of tracking performance in all subjects, which was most pronounced
      in the group of schizophrenic patients. Attention-enhancement, on the other hand,
      did not normalize performance in this group. In schizophrenic patients, mainly in
      the distraction condition, there was a moderate association between performance
      in tracking and tests presumably measuring prefrontal functions. Tracking
      accuracy from both conditions was related to general motor performance as
      measured by the Neurological Evaluation Scale. It was concluded that in
      schizophrenic patients attentional factors (distraction) may contribute to eye
      tracking impairment, and that the impairment may be viewed as an aspect of
      general motor dysfunctions.

PMID- 7803531
TI  - "Patterns of comorbidity" among DSM-III-R and ICD-10 personality disorders as
      observed with a new inventory for the assessment of personality disorders.
AB  - Although DSM-III-R and ICD-10 suggest the assignment of multiple personality
      diagnoses, a high degree of overlap may be an indicator of insufficiently
      distinct and too inclusive types of personality. We studied this problem with a
      new inventory in an unselected clinical sample. The Aachen List of Items for the
      Registration of Personality Disorders (AMPS) integrates the different types of
      disordered personality according to DSM-III-R, ICD-10, and four subaffective
      categories, which largely follow the typologies of Kraepelin, K. Schneider, and
      Kretschmer. The prevalence rate of each personality disorder was calculated in a
      consecutive group of 231 patients. Patterns of comorbidity were computed using
      odds ratios. More than one personality disorder was found in 41% according to DSM
      III-R. ICD-10 showed a significantly higher degree of overlap. Interesting
      comorbidity patterns are discussed in comparison with several North American
      studies. Results indicate that clear-cut categorical personality diagnoses are
      not likely to be set up.

PMID- 7803533
TI  - Gastrointestinal tract.

PMID- 7803534
TI  - Cardiotoxicity of chemotherapy.
AB  - With the use of hematologic support (colony stimulating factors and autologous
      bone marrow transplantation) for the control of chemotherapy-induced
      myelosuppression, more intensive strategies have been developed using higher
      doses, multidrug combinations, or more prolonged treatments. As a consequence of
      this approach, nonhematologic toxicities are more frequently dose-limiting and
      among them cardiotoxicity is of special concern. The spectrum of drugs associated
      with significant cardiotoxicity is extending, and each drug incriminated has its
      own cardiotoxicity profile. Various directions have been explored in experimental
      and clinical research for a better understanding of the physiopathology of drug
      induced cardiotoxicity and the clinical characterization of agents involved in
      order to accurately assess risk factors and to preclude or overcome
      cardiotoxicity by means of cardioprotective agents or other means. The recent
      developments surrounding anthracycline or 5-fluorouracil cardiotoxicity are
      remarkable examples of these different strategies.

PMID- 7803535
TI  - Vascular toxicity associated with chemotherapy and hormonotherapy.
AB  - Vascular complications associated with chemotherapy and hormonotherapy are being
      reported with increasing frequency. Such vascular toxicity is clinically
      heterogenous, ranging from asymptomatic venous lesions to fatal hepatic
      venoocclusive disease of the liver. Putative mechanisms for such toxicity include
      drug-induced endothelial cell damage, perturbation of the clotting cascade,
      platelet activation and aggregation, alteration of thromboxane-prostacyclin
      homeostasis, and dysregulation of cytokines. Better documentation of the
      incidence and types of vascular toxicity and studies to help elucidate the
      pathogenesis and management of such toxicity are needed.

PMID- 7803536
TI  - Graft-versus-host disease.
AB  - Combinations of drugs such as methotrexate, cyclosporin A, and prednisone have
      reduced the incidence of graft-versus-host disease (GVHD) to 20% to 30%. However,
      GVDH remains a major complication (up to 90%) following allogeneic bone marrow
      transplantation from unrelated or mismatched donors. GVHD is now understood as a
      two-step phenomenon: first, the activation of specific cytotoxic T cells and
      second, the release of several cytokines. Recent treatment modalities, including
      new immunosuppressors, T-cell depletion, and anticytokine monoclonal antibodies
      are discussed.

PMID- 7803537
TI  - Cytogenetics and experimental models of sarcomas.
AB  - Many sarcomas contain characteristic chromosome translocations that result in the
      fusion of genes from two different chromosomes. This review focuses on the
      translocated genes that have been identified recently in Ewing's sarcoma,
      peripheral primitive neuroectodermal tumor, clear cell sarcoma, alveolar
      rhabdomyosarcoma, and myxoid liposarcoma. Each of these fusion genes encodes a
      DNA transcription factor that presumably regulates the function of other genes.
      Thus, a common mechanism of oncogenesis has been defined in histologically
      disparate varieties of sarcoma.

PMID- 7803538
TI  - Diagnosis and treatment of soft tissue sarcomas in adults.
AB  - Our knowledge of the molecular biology of sarcomas has progressed considerably
      over the past year, with major emphasis on the role of p53 and MDM2 gene
      mutations. Further studies on drug resistance mechanisms and the role of MDR1
      expression in sarcomas have been reported. The investigations using different
      imaging techniques as ways of predicting tumor necrosis more accurately than our
      current response measurements after therapy have led to promising results. The
      many clinical phase II studies with new drugs led to the identification of
      taxotere as a new active agent against soft tissue sarcomas. Similar impressive
      results, such as those obtained with isolated limb perfusion in melanoma, have
      been reported in limb sarcomas with an identical regimen. The activity of
      ifosfamide in pretreated patients, administered at an increased dose, is
      suggestive of dose dependency. The improved results in phase II studies of dose
      intensive chemotherapy with the support of colony-stimulating factors are
      encouraging and these regimens are now being investigated in the adjuvant
      setting.

PMID- 7803539
TI  - Osteosarcoma and other tumors of bone.
AB  - Steady progress has been made in the identification of genetic alterations and
      prognostic factors in osteosarcoma. Imaging studies continue to be employed not
      only for preoperative staging, but to quantify factors such as tumor bulk and
      tumor response to neoadjuvant chemotherapy. Although there have been no major
      refinements of local or systemic therapy, continuing research into novel agents
      (eg, liposomal muramyl, tripeptide phosphatidylethanolamine, and antisense
      oligonucleotides to insulin-like growth factor receptors) hold promise for new
      therapies for this disease in the future.

PMID- 7803540
TI  - Ewing's sarcoma and peripheral primitive neuroectodermal tumor.
AB  - Disease-free survival for patients with small sarcomas of bone has been
      impressively improved with the use of intensive combination chemotherapy and safe
      local control with surgery or radiation. The ability of monoclonal antibodies to
      recognize different antigens has allowed new insights into the histogenesis and
      has distinguished a neural variant now referred to as malignant peripheral
      neuroectodermal tumor. Both entities share the translocation t(11;22) (q24;q12)
      as a constant phenomenon. The breakpoint region has now been cloned, allowing for
      molecular identification and detection of tumor cells and opening a new era of
      diagnostic and staging possibilities. Patients with disseminated disease, either
      at diagnosis or in relapse, have benefitted from megatherapy regimens followed by
      bone marrow or peripheral stem cell rescue. However, this approach is still under
      investigation and remains to be standardized.

PMID- 7803541
TI  - Rhabdomyosarcoma and other soft tissue sarcomas of childhood.
AB  - The past year has seen the publication of several important findings regarding
      the epidemiology, molecular biology, and treatment of pediatric rhabdomyosarcoma
      and other childhood soft tissue sarcomas. These research advances will help us
      better understand the mechanisms involved in tumor development and progression,
      tailor therapy according to specific pretreatment tumor biologic characteristics,
      and develop novel treatments for rhabdomyosarcoma.

PMID- 7803542
TI  - Colorectal cancer: a model of discovery in common human cancers. Commentary.

PMID- 7803543
TI  - Advances in the genetics and molecular biology of colorectal tumors.
AB  - Fascinating progress has been made in the past 2 years in our understanding of
      the genetic alterations associated with colorectal cancer predisposition and
      development. First, the genotype-phenotype relationship of the cancer
      susceptibility syndrome associated with familial adenomatous polyposis has been
      shown to depend on mutation type. Second, hereditary nonpolyposis colorectal
      cancer syndromes have been recognized as being frequently associated with a
      defect in the DNA mismatch-repair pathway. A gene on chromosome 2 called hMSH2,
      which demonstrates homology with the bacterial repair gene MutS, has been shown
      to be altered in some families with hereditary nonpolyposis colorectal cancer. A
      defect on chromosome 3 may act by impairing the same pathway. Genotyping of
      particular loci, termed microsatellite, provides an easy identification of tumors
      deficient in mismatch repair. Third, the mechanisms by which the inactivation of
      tumor-suppressor genes such as p53 and APC may contribute to the tumorigenic
      process have begun to be elucidated. These different discoveries will have
      important impacts in the prevention and management of colorectal carcinoma, one
      of the most frequent human cancers.

PMID- 7803544
TI  - Chemotherapy of advanced gastrointestinal cancer.
AB  - Pancreatic, gastric, and colorectal carcinomas are diagnosed in 200,000 Americans
      each year. Therapeutic options for patients with advanced disease are limited;
      conventional chemotherapy is palliative and produces complete responses in only a
      few patients. Clinical research has focused on the evaluation of investigational
      new drugs, combination regimens, and biochemical modulation of fluorouracil.
      Unfortunately, the results of recent phase II studies of new agents have been
      disappointing. The exception is CPT-11, a topoisomerase I inhibitor, which showed
      promising activity in colorectal cancer (in including patients who had failed
      prior fluorouracil therapy). Modified regimens of fluorouracil and methotrexate
      with either doxorubicin alone or with epirubicin and cisplatin were associated
      with response rates approaching 50% in patients with gastric cancer, but appeared
      to be less toxic than previously published regimens. A randomized trial comparing
      fluororacil alone or with oral leucovorin allowed early dose escalation according
      to individual tolerance; the response rate to fluorouracil alone (23%) was higher
      than that reported in previous phase III trials, suggesting the importance of
      using adequate doses to produce toxicity in terms of clinical response. Hepatic
      arterial infusion of floxuridine was associated with a 39% response rate in
      colorectal cancer patients with disease confined to the liver for whom systemic
      fluorouracil therapy had failed, suggesting this approach is a reasonable
      therapeutic option in carefully selected patients.

PMID- 7803545
TI  - Adjuvant therapy for gastrointestinal cancer.
AB  - Perioperative adjuvant treatment with chemotherapy or radiation therapy has been
      investigated for colon, rectal, gastric, esophageal, and pancreatic cancers. To
      date, conclusive benefit had been shown only for colon and rectal cancers.
      Demonstration that adjuvant therapy can result in reductions in tumor recurrence
      and cancer death after surgery for large bowel cancer is a major therapeutic
      advancement, and current clinical trials may yield further incremental
      improvements. Standard recommendations for adjuvant treatment exist for patients
      with colorectal cancers who do not take part in these clinical studies. Several
      factors complicate the assessment of adjuvant therapy for gastric, esophageal,
      and pancreatic cancers. Some regimens have appeared to offer promise of improved
      postsurgical outcome, but no adjuvant treatment has established benefit in these
      sites.

PMID- 7803547
TI  - [Cell death].

PMID- 7803546
TI  - Biology, diagnosis, and treatment of neuroendocrine tumors of the
      gastrointestinal tract.
AB  - Neuroendocrine tumors constitute only 2% of all malignant gastrointestinal tumors
      but have attracted a lot of scientific interest during the past decade. These
      tumors are excellent models for studies of new diagnostic and therapeutic tools.
      During the past year, major breakthroughs have been made in the areas of both
      diagnosis and therapy, but in particular, the development of somatostatin
      receptor scintigraphy and positron emission tomography have been major
      contributions to the diagnosis, localization, and tumor biology. The introduction
      of somatostatin analogues and interferons alone, or in combinations, have further
      improved the quality-of-life for patients with these tumors and probably has also
      prolonged the overall survival. Recent data on the expression of various growth
      factors, receptors, oncogenes, and tumor-suppressor genes have increased our
      understanding about the tumor biology. However, we are just at the beginning and
      to further improve the clinical management of these patients we have to put more
      effort into areas of molecular genetics and growth regulation of these tumors.
      This review discusses the recent developments in biology, diagnosis, and
      treatment of gut neuroendocrine tumors.

PMID- 7803548
TI  - [High prevalence of hepatitis B and C markers in an indigent community in
      Caracas, Venezuela].
AB  - Hepatitis B and C serological markers were evaluated in indigent patients living
      in a workhouse in Caracas, Venezuela. Three out of 146 specimens were reactive
      for HBsAg (2.1%) and 41 for anti-HBc (28%). Eight sera were reactive for
      antibodies against HCV, and 7 were confirmed by immunoblot assays (4.8%). Four
      out of these 7 HCV-positive sera were also HCV-RNA positive. The prevalence for
      viral hepatitis markers was significantly higher than that found in blood donor
      population in Caracas. The probable risk factors associated with this high
      prevalence of blood-borne viral hepatitis were: promiscuity, transfusion, drug
      addiction, alcoholism and history of reclusion. This high prevalence of hepatitis
      B and C compels the precaution for medical and paramedical staff attending this
      kind of patients.

PMID- 7803550
TI  - [The use of sublingual captopril in hypertensive crises].
AB  - The purpose of this study was to evaluate the antihypertensive efficacy of
      captopril (C) and its correlation with body mass index (BMI), age and initial
      blood pressure (BP) in hypertensive crises. The time of the beginning of the
      antihypertensive effect of C and its side effects were evaluated. Twenty
      patients, aged between 22 and 59 years, were included in this investigation. BP
      was measured after 15 min of rest; age, weight and height were recorded and BMI
      was calculated using the standard formula (Kg/m2). Patients were not taking
      antihypertensive medications. After the placebo was given to the patients, BP was
      measured at 30 and 60 min. Sublingual captopril 25 mg was administered and BP was
      again measured at 5, 10, 15, 30, 60, 120 y 240 min. There was not statistically
      significant difference between the values of BP before and after placebo. A
      significant decrease was observed post C, from 182.6/123.6 to 174.6/117.3 (p:SN/p
      < 0.02) in 10 min., to 169.9/114.9 (p < 0.04/p < 0.001) in 15 min., to
      167.7/112.2 (p < 0.02/p < 0.0001) in 30 min., to 164.3/108.8 (p < 0.002/p <
      0.0001) in 60 min., to 156.9/106.5 (p < 0.0001/p < 0.0001) in 120 min., to
      161.3/107.0 (p < 0.0002/p < 0.0001) in 240 min. In 15 patients there was a
      decrease in diastolic BP > or = 5 mmHg, 10 min. post C. No correlation was found
      between decrease in BP and age, nor with BMI. Pearson r correlation index between
      the decrease in systolic BP and initial systolic BP was 0.63 (p < 0.003) and
      between the decrease in diastolic BP and initial diastolic BP, 0.59 (p < 0.005).
      Secondary effects were mild and well tolerated. In conclusion, C effectively
      reduced BP in hypertensive crises. Because the efficacy of C, its rapid onset of
      action and minimal side effects, sublingual Captopril should be considered a
      first line drug for hypertensive crises.

PMID- 7803549
TI  - [Glycemic index and insulin response to the ingestion of precooked corn flour in
      the form of "arepa" in healthy individuals].
AB  - With the purpose of exploring the glucose and insulin responses to a breakfast
      composed of a complex carbohydrate (CC) in the form of a "arepa" prepared with
      precooked corn flour, with or without the addition of protein and fat (CC + P +
      F), we studied 6 healthy volunteers, ages ranging from 26-50 years and body mass
      index of 24.5 +/- 1.32. Three tests were performed on each individual: 1) 75 g
      OGTT, 2) Ingestion of 75 g of CC ("arepa") and 3) Ingestion of 75 g of CC + 6.7 g
      protein (low fat cheese) and 4 g fat (margarine). Glycemic values (glucose -
      oxidase method) and insulinemia (radioimmunoassay) were determined at basal, 30,
      60, 120, 180 and 240 min. Glucose (GA) and insulin (IA) areas, glycemic index
      (GI) and insulin/glucose ratio (I/G) were calculated. We found that the "arepa"
      has a high GI (71.5%) that it is increased, although not significatively to 140%
      with the addition of protein and fat. Total GA as well as IA obtained for CC and
      for CC + P + F were similar to OGTT, however the profiles of the glucose and
      insulin responses during CC and CC + P + F were less abrupt but more prolonged,
      resulting in a greater I/G ratio for OGTT in comparison with CC or CC + P + F
      during the initial steps. We conclude that GI of this corn bread ("arepa") is
      high in comparison to other complex carbohydrates and it is not altered by the
      addition of protein and fat. This is possibly due to glucose and insulin
      responses similar to that produced by OGTT.

PMID- 7803551
TI  - [Extramedullary intracranial solitary plasmocytoma. Report of 2 cases].
AB  - Multiple myeloma frequently affects the C.N.S with a high prevalence of spinal
      cord compression following vertebral neoplastic infiltration. On the other hand,
      solitary plasmacytomas, tumors that arise in a wide variety of locations due to
      the universal distribution of plasma cells, are infrequent within the cranial
      vault and rarely present as extramedullary lesions, arising from the intracranial
      soft tissues without affecting neighboring bony structures. Only 33 such cases
      have been reported in the medical literature. The authors report two additional
      cases of solitary intracranial, extramedullary plasmacytoma. Case 1.--54 year-old
      woman with a chief complaint of severe headache and behavioral changes of three
      months duration. C.N.S. imaging revealed a bifrontal mass lesion, arising from
      the anterior third of the falx cerebri. Case 2.--45 year old-man who complained
      of headache and blurred vision of a month duration C.N.S. imaging displayed a
      third ventricle mass lesion. In both cases the neuropathological diagnosis was
      extramedullary plasmacytoma. Postoperatively the confirmation of solitary
      intracranial plasmacytoma was achieved only after a thorough work-up to rule out
      the presence of neoplasm elsewhere in the body. Radiotherapy was given to both
      patients and follow-up has failed to reveal neoplastic disease 4 and 3 years,
      respectively, after the diagnosis.

PMID- 7803552
TI  - Determination of thymidine, uracil and p-aminobenzoic acid in bacteriological
      cultures by capillary zone electrophoresis.
AB  - A capillary zone electrophoresis assay has been developed which simultaneously
      separates and quantifies the bacterial metabolites thymidine, uracil and p
      aminobenzoic acid present at bacteriologically relevant concentrations in a
      supplemented minimal bacteriological medium. Sulphadiazine was used as the
      internal standard.

PMID- 7803553
TI  - Application of a Nafion-modified carbon paste electrode for the absorptive
      stripping voltammetric determination of fenoterol in pharmaceutical preparations
      and biological fluids.
AB  - The preconcentration of fenoterol on a Nafion-modified carbon paste electrode and
      its subsequent determination using differential pulse voltammetry is described.
      The effect of pH and percentage Nafion concentration on the accumulation
      behaviour of fenoterol was studied, and accumulation curves, calibration graphs
      and reproducibility studies at two different Nafion concentrations have been
      carried out in the range 2.5 x 10(-8)-5.0 x 10(-7) M fenoterol. A limit of
      detection in aqueous solutions, calculated using a signal-to-noise ratio (S/N) of
      3, was 9.0 x 10(-9) M. Application of the electrode to pharmaceutical
      preparations, without sample pretreatment, resulted in acceptable deviation from
      the stated concentration (RSD = +/- 3.81%, n = 4). For more complex matrices, a
      suitable extraction procedure was developed, resulting in recoveries of > 90%
      (urine) and > 75% (serum).

PMID- 7803554
TI  - Excretion of 3-hydroxy-diflunisal as a monosulphate conjugate--identification
      using ESI-MS.
AB  - Electrospray-ionization mass spectrometry was used to identify a novel, highly
      polar metabolite of diflunisal isolated from Gunn rat urine. Negative ion spectra
      were obtained of the sulphate conjugate of diflunisal and the new metabolite,
      which was identified as a sulphate conjugate of 3-hydroxydiflunisal.

PMID- 7803555
TI  - A direct two-site peroxidase-based enzyme-linked immunosorbent assay for
      proinsulin.
AB  - A non-competitive sandwich assay using an anti-C-peptide IgG and an anti-insulin
      IgG was developed to measure fasting levels of proinsulin in human serum. The
      former antibody provided the lower layer in a sandwich immunoassay, the upper
      layer being composed of an anti-insulin IgG-horse radish peroxidase conjugate.
      The assay showed negligible cross reactivity at supraphysiological levels of
      insulin and C-peptide. The method enabled the estimation of proinsulin in fasting
      non-diabetic control subjects [13.7 +/- 1.6(4) pM] and in type 2 non-insulin
      dependent diabetic patients [23.2 +/- 1.1(8) pM].

PMID- 7803556
TI  - Chemiluminometric determination of choline-related substances in pharmaceutical
      preparations by dot-blot.
AB  - A simple and reliable method of assaying succinylcholine chloride, oxtriphylline
      (choline theophyllinate) and acetycholine chloride in pharmaceutical
      preparations, based on conversion to choline, is provided by combination of
      chemiluminometry of choline and dot-blot technique. Recoveries of 102 and 97% for
      choline chloride in Quelicin injection and Choledyl 200 tablets matrices,
      respectively, and of 99% for acetylcholine chloride in Miochol solution matrix
      could be achieved using simple choline chloride standards in phosphate buffer pH
      8.6. Accordingly, matrix-matched standards were found redundant. Favourable
      results obtained in preparations-matched media including limits of detection of
      37-39 pmol microliters-1 of choline chloride, together with accuracies of 0-2%
      and RSDs ranging from 4 to 7% are the further evidence of the suitability of the
      method.

PMID- 7803557
TI  - FT-IR measurement of mercaptoundecahydrododecaborate in human plasma.
AB  - A simple and rapid method for the quantitative measurement of
      mercaptoundecahydrododecarborate (BSH), (which presently is one of the most
      useful agents for Boron Neutron Capture Therapy) in human plasma was developed by
      using Fourier transform infrared spectroscopy. Different spacer thicknesses of
      the liquid sampling cell were examined and the optimal results were obtained by
      the 0.05 mm spacer. The subtraction of water absorbance from sample spectra
      resolved a B-H band at 2493 cm-1. The quantitative measurement of BSH was carried
      out by integration of the B-H band in the wavenumber range of 2534-2440 cm-1.
      However, at the lower BSH concentration range, a visual inspection of the
      spectrum to determine the wavenumber range was necessary so as to avoid any
      negative areas to be integrated. The lower limit of detection of BSH in aqueous
      solution and human plasma was 5 micrograms ml-1 (about 2.5 ppm of boron).

PMID- 7803558
TI  - Determination of sulphanilamide in milk by first-derivative and second-derivative
      spectrofluorimetry.
AB  - First-derivative and second-derivative spectrofluorimetric methods have been
      developed for the analysis of sulphanilamide (SAN) in milk, using an ethanol
      water (60:40, v/v) medium. Linear calibration plots were obtained over a
      concentration range of 30-120 ppb, with correlation coefficients greater than
      0.997. Relative standard deviations were within the range 1.6-3.6%. Limits of
      detection were 0.7-2.7 ppb. Recoveries of 90-102% were obtained. The derivative
      fluorescence methods are simple, rapid and sensitive and there is no interference
      from fluorescent impurities in the determination of low levels of SAN in milk.

PMID- 7803559
TI  - Analysis of bovine immunoglobulin G by capillary gel electrophoresis.
AB  - A method for the analysis of bovine immunoglobulin G (IgG) using sodium dodecyl
      sulphate capillary gel electrophoresis (SDS-CGE) has been described. Under the
      electrophoretic conditions employed, monomeric and dimeric IgG were readily
      resolved, as were light chain and heavy chain subunits, and heavy chain dimers in
      reduced samples. Molecular weights determined by SDS-CGE compared favourably with
      those measured by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS
      PAGE) and published values. Reproducibility of protein quantitation was achieved
      resulting in a relative standard deviation of approximately 13% and calibration
      was linear in the range of 0.2-3.5 mg ml-1 protein under the conditions used.

PMID- 7803560
TI  - Flow-injection determination of Novalgin using amperometric detection at a glassy
      carbon electrode.
AB  - An electroanalytical study of the oxidation of Novalgin (dipyrone) at a glassy
      carbon electrode in aqueous solution has been carried out. A flow-injection
      method with amperometric detection based on this oxidation process is also
      described. The influence of flow rate, coil length and injection volume on the
      sensitivity of the method was established. The calibration graph was linear
      within the range 3 x 10(-6)-3 x 10(-5) M in an ammonia buffer solution (pH 9) as
      a potential of 0.4 V versus an Ag/AgCl reference electrode. The sampling rate was
      54 samples h-1. The applicability of the method to the determination of Novalgin
      in pharmaceutical preparations was demonstrated by investigating the effect of
      potential sources of interference and by analysing commercial preparations.

PMID- 7803561
TI  - Characterization of submicron MCT o/w emulsions using sedimentation field-flow
      fractionation (FFF) with power field programming.
AB  - Sedimentation field-flow fractionation (SdFFF) operated with power-based field
      programming, was shown to be effective in the characterization of submicron
      investigational pharmaceutical emulsions. Field programming, in which the
      decrease of field strength with time gradually decreases the retention of sample
      components, extends the capabilities of sedimentation field flow fractionation in
      handling polydisperse and multicomponent samples. The emulsions were made of
      medium chain triglycerides (MCT) oil in water emulsified by phospholipids. They
      were analysed by different rates of field decay and different flow rates.
      Identical size distribution profiles were obtained under all circumstances, using
      the appropriate stop-flow times. Fractions were collected from the SdFFF eluting
      bands, and diameters were analysed by photon correlation spectroscopy, showing
      good agreement with values given by the FFF instrument at high flow rates and low
      rates of field decay. Accurate and highly reproducible size distribution profiles
      were obtained under various conditions. The detector response was shown to
      consist mostly of light scattering and was linear with concentration.

PMID- 7803562
TI  - Radioimmunoassay of drugs of abuse in hair. Part 1: Methadone in human hair,
      method adaptation and the evaluation of decontamination procedures.
AB  - A method suitable for the determination of methadone in human hair is presented.
      Adaptation and evaluation of a solid-phase I125 radioimmunoassay, designed for
      the quantitative measurement of methadone in urine, and development of a pre
      analytical wash procedure has enabled a specific, sensitive and accurate
      analytical procedure to be developed. The specificity of the antiserum towards
      other drugs or biologically active compounds is evaluated up to a concentration
      of 100,000 ng ml-1 and accuracy covering a range of 0-450 ng ml-1 is found to be
      within 6% of expected methadone concentrations prepared in both drug free hair
      extract and urine. Inter-assay relative standard deviation (RSD) at
      concentrations of 5.1, 76.0 and 247 ng ml-1 methadone are 5.5, 2.5 and 3.6%
      respectively (n = 10) and intra-assay RSD at concentrations 2.3, 25.2 and 217 ng
      ml-1 are 5.3, 3.6 and 6.8% (n = 5). The limit of detection is 0.5 ng ml-1.
      Extraction of control drug free hair samples spiked with methadone at
      concentrations of 100, 250 and 400 ng ml-1 achieved recoveries of 86, 80 and 89%,
      respectively. Control hair samples contaminated with methadone are examined under
      differing wash procedures to assess their effectiveness in the removal of
      methadone contaminant. A suitable pre-analytical wash regime is proposed for
      removal of contaminant derived from external or environmental sources. The
      mechanics of the wash action and contaminant application to the hair is
      discussed. It is concluded that the adapted radioimmunoassay and developed pre
      analytical decontamination procedure is a suitable technique to employ for the
      measurement of methadone in human hair, be it prescribed or abused, with
      concentrations expressed as ng methadone per mg hair.

PMID- 7803563
TI  - Colorimetric determination of cyclophosphamide and ifosphamide.
AB  - A simple colorimetric method for the determination of cyclophosphamide and
      ifosphamide in pure and in dosage forms is suggested. It depends on the reaction
      of the secondary amino group in both, with nitrous acid, thus forming a nitroso
      derivative which can be measured at 325 nm for cyclophosphamide and 335 nm for
      ifosphamide. Beer's law is obeyed with concentrations from 20 to 90 micrograms ml
      1 for cyclophosphamide and from 5 to 100 micrograms ml-1 for ifosphadmie, with
      repeatability of 99.83 +/- 0.256% and 99.72 +/- 0.649%, respectively. Application
      to different pharmaceutical preparations has shown no significant difference when
      compared with the B.P. 1988 method.

PMID- 7803564
TI  - Isolation and structural elucidation of an impurity of cefradine.
AB  - An impurity of unknown identity was isolated from commercial cefradine by liquid
      chromatography on poly (styrene-divinylbenzene) with HOAc (0.01 M)-CH3CN (94:6,
      v/v) as the mobile phase. The structure was elucidated as 4',5'-dihydrocefradine
      using nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS).
      The structure was confirmed by comparison with the chromatographic retention
      characteristics and photodiode-array detected ultraviolet spectrum of the
      synthetic compound and with its infrared, NMR and MS spectra. The presence of
      4',5'-dihydrocefradine in cefradine has not been described previously.

PMID- 7803565
TI  - Analytical and semi-preparative separation of diastereomeric lipid amino acid
      conjugates.
AB  - A series of biologically active peptides and their conjugates with lipidic amino
      acids were investigated by systematic change of the mobile phase composition
      using traditional octadecylsilica stationary phase and the newly developed
      Supelcosil LC-ABZ column. The mobile phases contained various concentrations of
      methanol and acetonitrile combined with 0.1% trifluoroacetic acid (TFA). Better
      peak shapes and higher resolution of the isomers could be observed when the
      mobile phase contained 0.1% TFA. More symmetrical peaks and much higher S values
      (slope of the log k' vs organic phase concentration plots) were obtained on the
      special reversed-phase column developed for anionic, basic or zwitterionic
      compounds. The optimum separation conditions were scaled up to a semi-preparative
      reversed-phase column (15 mm i.d.) to collect mg quantities of isomers for
      further studies.

PMID- 7803566
TI  - Application of an electrochemical detector with a graphite electrode to liquid
      chromatographic determination of penicillamine and captopril in biological
      samples.
AB  - A high-performance liquid chromatographic determination of penicillamine and
      captopril in rat serum, liver and kidney samples is described. An electrochemical
      detector with a graphite working electrode at a potential of +0.9 V vs the
      Ag/AgCl reference electrode is used for the detection system. Linear responses of
      the peak height to the amount of samples injected were obtained in a range of 0.1
      500 ng on-column and 0.5-500 ng on-column for penicillamine and captopril with
      correlation coefficients of 0.997 and 0.995, respectively. Detection limits at a
      signal-to-noise ratio of 3 were 20 and 300 pg for penicillamine and captopril,
      respectively. The graphite electrode has a long lifetime of about 4 months with
      continuous use, even with the high voltage supplied. The analytical application
      of this method to the determination of penicillamine and captopril in biological
      samples was successful.

PMID- 7803567
TI  - Improved LC assay for the determination of mitozantrone in plasma: analytical
      considerations.
AB  - Preliminary method development studies on mitozantrone (MTZ) revealed a number of
      characteristics which were found to be important in the analysis of patient
      samples for pharmacokinetic studies. MTZ rapidly bound to glass, particularly at
      low concentrations (< 10 ng ml-1), necessitating the use of silanized glassware
      or polypropylene tubes for the handling of all solutions containing MTZ. MTZ was
      also found to react with two commonly-used antioxidants; sodium metabisulphite
      and EDTA. However, solutions containing MTZ were found to be stabilized by the
      addition of ascorbic acid (0.5% w/v). In the absence of ascorbic acid, MTZ
      underwent rapid, biphasic degradation in plasma at 24 and 37 degrees C, with
      terminal half-lives of approximately 70 h. Ascorbic acid (0.5% 2/v) was found to
      stabilize plasma samples containing MTZ throughout work-up procedures and during
      frozen storage. The addition of ascorbic acid to the sample collection vial was
      also necessary to prevent MTZ degradation in the eluting solvent of the solid
      phase extraction system. Another important consideration was the requirement for
      an equilibration period of > 5 min after the addition of ametantrone (AM)
      internal standard to plasma samples. This was essential, since the slope of the
      calibration plot obtained using non-equilibrated plasma was approximately 30% of
      that obtained for calibration plots using equilibrated plasma, and would result
      in erroneous determination of MTZ plasma concentrations. The fully developed
      assay was rapid, precise and sensitive (relative errors at 1 ng ml-1 = 2.3%). MTZ
      concentrations determined using the LC method described in this report correlated
      well with an independently developed ELISA technique (r = 0.995, n = 20).

PMID- 7803568
TI  - Determination of DuP 128, an ACAT inhibitor and its sulphoxide and sulphone
      metabolites in human plasma by liquid chromatography.
AB  - A sensitive and specific high-performance liquid chromatographic (HPLC) method
      with fluorescence detection was developed for the simultaneous determination of
      DuP 128 (N'-(2,4-difluorophenyl)-N-[5-(4,5-diphenyl-1H-imidazol-2-ylthio)p entyl]
      N- hepthylurea), an ACAT inhibitor, its sulphone metabolite (XB277), and the
      separate determination of sulphoxide metabolite (XC164) in human plasma. After
      deproteinizing plasma samples with acetonitrile, the organic layer, created by
      adding approximately 0.25 g of NaCl, was removed, evaporated to dryness, and the
      residue then reconstituted with 400 microliters of acetonitrile. The acetonitrile
      layer was washed with 5 ml of hexane and then 50 microliters was injected into
      the HPLC. DuP 128 and XB277 were simultaneously quantified using a YMC basic
      column and fluorescence detection (lambda Ex = 270 nm and lambda Em = 385 nm).
      XC164 was quantified using a Waters microBondpack C18 reversed-phase column and
      fluorescence detection (lambda Ex = 270 nm and lambda Em = 365 nm). The
      relationship between the peak height and plasma concentrations best fit a power
      curve and showed an average correlation coefficient of > 0.99 over a
      concentration range of 1-200 ng ml-1 for DuP 128 and XC164 and 2.5-200 ng ml-1
      for XB277. Good intraday and interday assay precisions (RSD < 10%) and accuracy
      (< 14%) for all three compounds were observed. The methods were sufficiently
      sensitive and selective to quantify plasma concentrations of DuP 128 and its
      sulphoxide and sulphone metabolites after oral administration of single or
      multiple dose(s) of > 350 mg of DuP 128 to healthy subjects.

PMID- 7803569
TI  - High-performance liquid chromatographic determination of metaiodobenzylguanidine
      in whole blood and plasma of cancer patients.
AB  - An accurate and simple high-performance liquid chromatographic (HPLC) assay is
      presented for the quantitative determination of metaiodobenzylguanidine (MIBG) in
      human whole blood and plasma. The sample pretreatment involves a solid-phase
      extraction on Bakerbond SPE cyano columns. The HPLC system comprises a
      microBondapak C18 column and ammonium phosphate (pH4.0; 25 mM)-acetonitrile
      (80:20, v/v) as the mobile phase. Detection is performed by UV absorbance
      measurements at 254 nm. Linear regression with weighting factor l/chi 2 yielded
      the smallest sum of per cent relative concentration residuals over the
      concentration range of the assay (0.1-10 micrograms ml-1). MIBG levels, at the
      end of a 3-h infusion, in whole blood and plasma of carcinoid patients were
      measured and compared with the results obtained with radiodetection after
      addition of iodine-131-labelled MIBG.

PMID- 7803570
TI  - Fully automated assay for the determination of GR117289X in human plasma using
      mixed mode solid-phase extraction and high-performance liquid chromatography with
      ultraviolet detection.
AB  - GR117289X, 3-(3-Bromo-2-[2-(1H-tetrazol-5-yl)-phenyl]-bezofuran-5-yl methyl)-2
      butyl- 5-chloro-3H-imidazole-4-carboxylic acid, 1, is an angiotensin II receptor
      antagonist. A sensitive, accurate and precise assay for the determination of 1 in
      human plasma and validation data is described. The assay consists of a novel
      solid-phase extraction using Certify II followed by a reversed-phase gradient
      HPLC separation with UV detection. The extraction procedure has been fully
      automated by a Zymate XP robot and linked on-line to the HPLC system. The
      analytical range for the assay is 5-250 ng ml-1 over which the assay is linear
      and specific for 1 with respect to endogenous plasma components and its tetrazole
      N2 glucuronide, the major circulating metabolite 2. For the fully automated
      procedure the intra-assay data indicate a maximum bias and coefficient of
      variation across the calibration range of +8.0 and 9.4%, respectively. The inter
      assay data indicate a maximum bias and coefficient of variation across the
      calibration range of +8.0 and 11.1%, respectively. The extraction efficiency of
      the assay was approximately 75%. Both a manual and fully automated assay were
      applied to the analysis of 1 in plasma of volunteers from a number of clinical
      studies. The assay has been shown to be robust in sustained use over several
      months.

PMID- 7803571
TI  - Microassay of propranolol enantiomers and conjugates in human plasma and urine by
      high-performance liquid chromatography after chiral derivatization for
      pharmacokinetic study.
AB  - A microdetermination of propranolol enantiomers and of their glucuronide and
      sulphate conjugates in human plasma and urine by reversed-phase HPLC after chiral
      derivatization is described. After extraction from 100 microliters of plasma or
      urine with racemic 4-methylpropranolol as internal standard (I.S.), the
      enantiomers are derivatized with R(+)-phenylethylisocyanate as chiral
      derivatization reagent. Chromatography is performed on Novapak C18 column with
      fluorescence detection. Glucuronide and sulphate conjugates are cleaved prior to
      extraction by incubating, respectively, the samples with glucuronidase
      arylsulphatase and saccharic acid 1-4 lactone as specific glucuronidase
      inhibitor. The retention times of propranolol and I.S. enantiomer derivatives are
      short (tR = 5.5-6.2 min and 8.8-10.1 min, respectively). The diastereomeric
      derivatives are very stable and show good peak symmetry and resolutions (RS = 2
      and 2.2). The use of 4-methylpropranolol as I.S. improves significantly relative
      standard deviations (RSD: 1.7-5.1). Sensitivity is about 1 ng ml-1 per
      enantiomer. The method is applied to pharmacokinetic studies of racemic
      propranolol in human plasma and urine. S-propranolol and its conjugates show
      higher concentrations than R-propranolol and its conjugates in plasma and urine.

PMID- 7803572
TI  - Interference of mandelic acid with the determination of homatropine hydrobromide
      by second-order derivative spectroscopy.

PMID- 7803573
TI  - Stability of ganciclovir in blood samples.

PMID- 7803575
TI  - Tracheostomy in infants.

PMID- 7803574
TI  - Preparation and characterization of Cu(II)--lignocaine complex. Indirect
      estimation of lignocaine in pharmaceutical preparations by atomic absorption
      spectroscopy (AAS).

PMID- 7803577
TI  - Congenital tracheal stenosis.

PMID- 7803578
TI  - Tracheomalacia.

PMID- 7803576
TI  - Subglottic tracheal stenosis.
AB  - In dealing with subglottic stenosis in small children, meticulous and gentle
      techniques will yield the best results. It is easier to prevent than to treat
      subglottic stenosis. The use of endotracheal tubes of proper size (Fig 10) and
      meticulous management of the tube combined with careful extubation techniques may
      prevent progression of injury. If stenosis does develop, the lesions should be
      carefully assessed and described. Care must be taken in diagnostic procedures so
      that a rigid scope is not forced through an area of narrowing, thereby producing
      further injury. The old technique of rigid dilators may produce a shearing injury
      to the tracheal mucosa that is manifested by blood on the dilators. Intralesional
      injection of steroids also may be more injurious than helpful. The use of
      balloons with radial dilation has been more satisfactory. When granulation tissue
      is extensive, removal can be accomplished either with cup biopsy forceps or with
      the KTP laser. Minimizing iatrogenic injury by using the lowest possible wattage
      produces better results. When tracheoplasty is necessary, careful attention to
      technical details is essential. These details are described under the section on
      cartilage tracheoplasty. With difficult stenotic lesions, many techniques have
      been proposed, indicating that no one technique is universally successful. Thus,
      it is important to make careful assessment and description of the lesion along
      with an individualized approach following generally accepted guidelines.

PMID- 7803579
TI  - Long-gap esophageal atresia.

PMID- 7803580
TI  - Congenital diaphragmatic hernia in 1994: a hard look at the need for 'emergency
      surgery'.

PMID- 7803581
TI  - Extracorporeal membrane oxygenation.

PMID- 7803582
TI  - Primary tumors of the chest wall and mediastinum in children.

PMID- 7803583
TI  - Gastroesophageal reflux.
AB  - GER is a major pediatric disease. The respiratory, nutritional, and inflammatory
      complications of this disease process, invisibly hidden in the gastroesophageal
      junction, have a profound effect on the quality and sometimes the very life of
      infants and children. The astute pediatrician and surgeon should always keep this
      disease process in mind when dealing with these problems of children. Having a
      high suspicion of GER is often necessary to find this hidden enemy. The Nissen
      fundoplication and the Thal fundoplication are equally successful in the
      treatment of GER in children. However, the complication rate with the Nissen
      fundoplication is higher than with the Thal. We feel that the Thal does an
      outstanding job of treating GER while maintaining normal gastroesophageal
      function in the developing child, and is therefore our operation of choice for
      GER.

PMID- 7803584
TI  - Fetal cystic adenomatoid malformation of the lung: diagnosis, perinatal
      management, and outcome.

PMID- 7803585
TI  - International craniofacial bibliography.

PMID- 7803586
TI  - The neurosurgeon and craniosynostosis.

PMID- 7803587
TI  - Treatment of positional plagiocephaly with dynamic orthotic cranioplasty.
AB  - Dynamic orthotic cranioplasty (DOC) was developed to treat asymmetrical head
      shape of a nonsynostotic origin, which is defined by the term positional
      plagiocephaly. These positional deformations have been found to correlate with a
      number of environmental factors. Infants with positional plagiocephaly may
      exhibit complex multistructural asymmetry affecting the cranial vault, face, and
      skull base, or expression may be local in nature. Between 1988 and 1993, we
      performed DOC on 124 infants with positional plagiocephaly. Through clinical,
      anthropometric, radiographic, and statistical evaluation, we found that DOC
      corrects positional deformation of the cranial vault, skull base, and upper face,
      with no evident relapse following treatment. The design and the global approach
      to deformation address a wide spectrum of abnormal head shapes. The procedure is
      dynamic and customized, and it does not rely on passive growth alone for
      improvement.

PMID- 7803588
TI  - The effect of periosteal preservation on osteogenesis in a canine rib autograft
      model: tetracycline fluorescence incident photometry.
AB  - In the first portion of this study, we describe a new technique, tetracycline
      fluorescence incident photometry (TFIP) for quantifying new bone formation. In
      this portion, we use routine histology, Microfil vascular injection, and
      tetracycline incidence fluorescence (TFIP) to determine the effect of periosteal
      preservation on bone formation in canine rib autografts. We found that periosteal
      preservation significantly enhanced new bone formation in both cortical and
      trabecular bone (83-70% of control) when compared with autografts without the
      periosteum (76-60% of control) (p < 0.05). In addition, periosteal preservation
      favorably influenced graft revascularization. We found that the periosteum of the
      transferred rib autografts was made up of 3 distinct layers: (1) the inner
      (cambial) layer of osteogenic cells, (2) the middle (fibrous) layer of osteogenic
      reserve cells, and (3) the outer vascular network of arterioles and venules,
      which communicate with the trabecular vessels internally. This outer vascular
      network has not been previously described in transferred bone grafts and is
      responsible for early graft revascularization.

PMID- 7803590
TI  - Cranial reconstruction in osteogenesis imperfecta.
AB  - Although osteogenesis imperfecta (OI) is recognized as a cause of
      craniosynostosis, therapeutic endeavors have not been reported. We present an 8
      month-old girl with type 3 OI, in whom bilateral occipital flattening, biparietal
      widening, and frontal narrowing were effectively managed with a combined surgical
      release and reconstruction and molding cap therapy. The quality of the calvarial
      bone in OI requires a modified approach to the conventional bone techniques
      commonly used in the correction of craniosynostosis deformities.

PMID- 7803589
TI  - Comparison of various delivery systems for demineralized bone matrix in a rat
      cranial defect model.
AB  - Demineralized bone matrix (DBM) has been successfully used as a substitute for
      bone grafting. Autogenous bone grafts may cause site morbidity and undergo
      significant resorption. DBM may overcome these problems, but it has no mechanical
      stability until bone formation has occurred. We tested various alloplastic
      implants (i.e., Surgicel, polydioxanone [PDS], porous polyethylene [Medpor], and
      Gelfoam) in combination with DBM and compared it with DBM alone in a 9 x 9 mm rat
      cranial defect model. Histological and biomechanical measurements were performed
      at postoperative month 2. Among the study groups, Gelfoam/DBM inhibited bone
      formation to varying degrees and was the only group that displayed an
      inflammatory response. Mechanical pushout tests using a servohydraulic testing
      frame were conducted. The Medpor/DBM implant displayed the strongest support at 2
      months; maximum load was 95% of intact skull. Surgicel/DBM and DBM alone were
      comparable; maximum load was 66% of intact skull. Gelfoam/DBM and PDS/DBM
      displayed the weakest support (48% of intact skull). We conclude that, after 2
      months of implantation, alloplastic/DBM composites provide osseous structural
      integration. Gelfoam/DBM is not an effective delivery system for DBM in our
      model.

PMID- 7803591
TI  - The frontal sinus in frontoethmoidal meningoencephaloceles.
AB  - We performed a review of all patients with frontoethmoidal meningoencephaloceles
      (FEME) in whom frontal sinus development would be expected to be complete.
      Frontal sinus absence is the predominant finding. The potential role of the FEME
      in producing a structural blockage to normal frontal sinus development is
      suggested. Surgical correction of the encephalocele should include augmentation
      of the glabella to compensate for the combined effects of the FEME and the
      surgical osteotomies in this region.

PMID- 7803593
TI  - Form-fitting fixation.
AB  - Use of rigid fixation systems in craniomaxillofacial surgery has significantly
      improved clinical results. We describe the technical application of utilizing
      rigid fixation systems in the actual process of reshaping bone flaps and grafts.
      We call the use of this technique form-fitting fixation, and describe its
      application in a wide variety of craniofacial reconstructions.

PMID- 7803592
TI  - Cartographic mapping of the skull from computed tomography scans.
AB  - Contemporary imaging technologies (i.e., computed tomography [CT] and magnetic
      resonance imaging) generate an overwhelming amount of data. Salient features from
      these data must be abstracted and presented to facilitate anatomical
      comprehension and imaging utility. Three-dimensional surface and volumetric
      reformations of CT data have extended the integration of high resolution CT data
      to the study and management of craniofacial deformities. Nonetheless,
      conventional displays of such imaging require multiple images to assess symmetry,
      sutural status, and traumatic disruption of the skull. We therefore devised a
      methodology to apply cylindrical cartographic mapping for display of the entire
      skull on 1 image. Cartographic mapping was used to evaluate the skulls of
      patients with congenital asymmetry due to hemifacial microsomia,
      craniosynostosis, and complex comminuted craniofacial fractures. Cartographic
      mapping does effectively display the entire skull in 1 image. Such images are
      useful to assess craniofacial symmetry, sutural status, and comminuted fractures.
      However, cartographic images cannot define anterior-posterior relationships, and
      they must be augmented with more traditional data displays for assessment of
      intermaxillary and jaw-cranial base relations.

PMID- 7803594
TI  - Unicortical critical size defect of rabbit tibia is larger than 8 mm.
AB  - The critical-size defect is important as an experimental model to test bone
      repair materials. Guided tissue regeneration is an established method for tissue
      regeneration within periodontal surgery. Bony defects covered by a membrane are
      allowed to be filled by bony tissue. Healing of 8-mm unicortical trephine defects
      was tested in Copenhagen White rabbit tibia using 3 different membranes. The
      critical-size defect in Copenhagen White rabbit tibia is larger than 8 mm,
      because control defects 8 mm in diameter healed spontaneously. However, it is
      anatomically not possible to create defects larger than 8 mm in an adult
      Copenhagen White rabbit tibia.

PMID- 7803595
TI  - Is impulsive aggression a disorder of the individual or a social ill? A matter of
      metaphor.

PMID- 7803596
TI  - Neuroendocrine effects of light therapy in late luteal phase dysphoric disorder.
AB  - In 20 late luteal phase dysphoric disorder (LLPDD) and in 11 normal control (NC)
      subjects, circadian profiles of cortisol, prolactin, thyrotropin-stimulating
      hormone (TSH), and core body temperature were measured during midfollicular (MF)
      and late luteal (LL) menstrual cycle phases and after 1 week of light therapy
      either with (1) bright (tau 2500 lux) white morning (6:30 AM to 8:30 AM), (2)
      bright white evening (7 PM to 9 PM) or (3) dim (< 10 lux) red evening light,
      randomly administered in three separate luteal phases. In NC but not PMDD
      subjects, the cortisol peak significantly delayed in the LL compared with the MF
      phase. In PMDD, prolactin peak and amplitude were higher, prolactin acrophase
      earlier, and temperature amplitude higher during both the MF and LL phases. After
      light treatment, prolactin amplitude remained higher in LLPDD than in controls.
      In both groups, bright light shifted the cortisol acrophase, and AM light
      increased the prolactin nadir. Bright PM light increased the TSH nadir in LLPDD,
      but decreased it in controls. Thus, menstrual cycle phase, diagnosis, and light
      therapy may differentially affect neuroendocrine systems.

PMID- 7803597
TI  - Selective reductions in prefrontal glucose metabolism in murderers.
AB  - This study tests the hypothesis that seriously violent offenders pleading not
      guilty by reason of insanity or incompetent to stand trial are characterized by
      prefrontal dysfunction. This hypothesis was tested in a group of 22 subjects
      accused of murder and 22 age-matched and gender-matched controls by measuring
      local cerebral uptake of glucose using positron emission tomography during the
      continuous performance task. Murderers had significantly lower glucose metabolism
      in both lateral and medial prefrontal cortex relative to controls. No group
      differences were observed for posterior frontal, temporal, and parietal glucose
      metabolism, indicating regional specificity for the prefrontal deficit. Group
      differences were not found to be a function of raised levels of left-handedness,
      schizophrenia, ethnic minority status, head injury, or motivation deficits in the
      murder group. These preliminary results suggest that deficits localized to the
      prefrontal cortex may be related to violence in a selected group of offenders,
      although further studies are needed to establish the generalizability of these
      findings to violent offenders in the community.

PMID- 7803598
TI  - Adrenal weight and morphology in victims of completed suicide.
AB  - Several lines of evidence have implicated hypothalamic-pituitary-adrenal (HPA)
      axis dysfunction in major depression and suicidal behavior. In the present study,
      the weight and morphology of postmortem adrenal glands were compared between
      suicide victims and sudden death, nonpsychiatric controls. The mean adrenal
      weight of the combined left and right glands was significantly higher in the
      suicide group; this difference was accounted for specifically by increases in
      left adrenal weight of suicides compared with the control group. There was a
      positive correlation between adrenal weight and total cortical thickness in both
      left and right glands, providing direct evidence that increased adrenal weight in
      suicide victims is due to cortical hypertrophy. The finding of left-right adrenal
      weight asymmetry in suicides is consistent with the hypothesis of abnormal
      lateralized input from higher control centers of the HPA axis.

PMID- 7803599
TI  - Frontal and parietal metabolic disturbances in unipolar depression.
AB  - The authors investigated brain glucose utilization using positron emission
      tomography (PET) in 12 normal volunteers and 12 unipolar unmedicated depressed
      patients (six endogenous; six nonendogenous) following injection of [18F]fluoro
      deoxyglucose (FDG). Compared by analyses of variance, absolute and relative
      regional glucose metabolic rates appeared different in depressed patients and
      control subjects, especially in parietal and frontal lobes. In patients with
      unipolar depression, metabolic rates were increased in the orbital part of the
      frontal lobe and decreased in a frontal dorsolateral area. The metabolic supero
      basal gradient calculated in the frontal cortex was significantly lower in
      depressed patients than in normal subjects. Decreased glucose metabolism was also
      observed in the parietal cortex of depressed patients. No differences in glucose
      metabolic rates have been detected between endogenous and nonendogenous patients.
      No correlation has been found between the metabolic data and the Hamilton Rating
      Scale.

PMID- 7803600
TI  - Cortisol suppression by dexamethasone in the healthy elderly: effects of age,
      dexamethasone levels, and cognitive function.
AB  - The effects of age, cognitive function (measured by Cambridge cognitive
      examination (CAM-COG) score); and dexamethasone (DEX) levels on the dexamethasone
      suppression test were studied in 33 healthy older subjects (age 51-96). Three
      subjects (9.1%) were nonsuppressors and were older and had lower CAMCOG scores
      than the 30 suppressors. Significant correlations were observed between natural
      log-transformed postdexamethasone cortisol (LNCOR) levels and age (r = 0.40) and
      CAMCOG score (r = -0.45). Multiple regression analysis was used to investigate
      the relationship between LNCOR, age, DEX levels, and CAMCOG score. Age and DEX
      combined explained 41% of the variance in LNCOR values, whereas CAMCOG score and
      DEX levels explained 44% variance. As age and CAMCOG were highly correlated (r = 
      0.72), both together did not significantly improve the fit of regression equation
      (47% variance explained). These findings suggest an association between advancing
      age, impaired glucocorticoid feedback, and cognitive dysfunction in healthy human
      subjects. Although any causal connection remains to be demonstrated, results
      would be consistent with the "glucocorticoid cascade" hypothesis of human aging.

PMID- 7803601
TI  - Serotonin and alcohol intake, abuse, and dependence: findings of animal studies.
AB  - Despite a relatively large body of literature on the role of the neurotransmitter
      serotonin (5-hydroxytryptamine, or 5-HT) in the regulation of alcohol intake, the
      functional significance of serotonergic neurotransmission and its relationship to
      alcohol intake, abuse, and dependence remains to be fully elucidated. In part two
      of this review, the experimental (animal) data is summarized along two lines: the
      effects of serotonergic manipulations on the intake of alcohol, and the effects
      of acute and chronic alcohol intake, as well as the withdrawal of chronic
      alcohol, on the serotonergic system. It is concluded that serotonin mediates
      ethanol intake as a part of its larger role in behavior modulation, such that
      increases in serotonergic functioning decrease ethanol intake, and decreased
      serotonergic functioning increases ethanol intake. Ethanol produces transient
      increases in serotonergic functioning that activate the mesolimbic dopaminergic
      reward system. The results are discussed in light of recent theories describing
      the regulatory role of serotonin in general behavior.

PMID- 7803602
TI  - The relationship between mood and daily hours of sunlight in rapid cycling
      bipolar illness.

PMID- 7803603
TI  - Plasma and CSF HVA levels in panic patients with comorbid social phobia.

PMID- 7803604
TI  - Evidence for familial association of psychiatric disorders and epilepsy.

PMID- 7803605
TI  - Purification of bovine estrus-associated protein and localization of binding on
      sperm.
AB  - An oviduct-specific, estrus-associated glycoprotein (EAP) of 85-95 kDa is
      detectable in both conditioned medium (CM) from oviductal explants and cannula
      derived oviductal fluid (ODF). The objectives of this study were to purify EAP
      from both ODF and CM, to characterize the glycosylation of EAP, and to localize
      binding of EAP on sperm. EAP was purified from ODF by ammonium sulfate
      precipitation and ammonium sulfate back-extraction followed by electroelution
      from one-dimensional SDS-PAGE gels. EAP was recovered from CM by electroelution
      from SDS-PAGE gels. Purified EAP was used as antigen to produce polyclonal
      antibodies (anti-EAP), and the specificity of anti-EAP was demonstrated as a
      single band in Western blots of ODF. N-linked sugar residues were enzymatically
      removed from EAP purified from ODF. The resulting molecule was 7 kDa smaller and
      was similar in molecular mass to EAP derived from CM. Sperm were incubated with
      35S-proteins synthesized by oviductal explant cultures. Autoradiographs of
      solubilized sperm membranes contained a 90-95-kDa protein that was confirmed by
      Western blotting to be EAP. EAP was localized on permeabilized membranes of sperm
      incubated in ODF by immunocytochemistry using polyclonal anti-EAP. EAP was bound
      to the head and middle piece of 97% of the sperm incubated for 4 h in ODF. From
      these results, we concluded that N-linked sugars account for approximately 8% of
      the molecular mass of ODF-derived EAP and that EAP binds to the head and middle
      piece of sperm.

PMID- 7803606
TI  - Receptor binding of gonadotropin-releasing hormone antagonists that inhibit
      release of gonadotropin-II and growth hormone in goldfish, Carassius auratus.
AB  - In goldfish, GnRH stimulates gonadotropin-II (GTH-II) and growth hormone (GH)
      release. The two native forms of GnRH, salmon GnRH (sGnRH) and chicken GnRH-II
      (cGnRH-II), bind to two classes of GnRH binding sites: high-affinity/low-capacity
      sites and low-affinity/high-capacity sites. Our previous in vitro perifusion
      studies of goldfish pituitary fragments showed that [Ac-delta 3-Pro1, 4FD-Phe2, D
      Trp3,6]-mGnRH (analog E), [Ac-delta 3-Pro1, 4FD-Phe2, D-Trp3,6]-sGnRH (analog C),
      and [Ac-D(2)Nal1, 4Cl-D-Phe2, D-(3)Pal3,6]-cGnRH-II (analog N) inhibited both
      sGnRH- and cGnRH-II-stimulated GTH-II and GH release. Interestingly, analog C
      stimulated GH release but not GTH-II release. The objectives of the present study
      were 1) to test the site of action of GnRH antagonists in goldfish, 2) to test
      the relationship between receptor binding affinity of antagonists and their in
      vitro inhibitory potencies and apparent duration of action, and 3) to compare the
      binding characteristics of analog C with its differential action on GTH-II and GH
      release. As in previous studies, analog E suppressed sGnRH-stimulated GTH-II and
      GH release from perifused pituitary fragments. Similarly, analog E suppressed
      both sGnRH- and cGnRH-II-stimulated GTH-II and GH release from perifused
      dispersed goldfish pituitary cells, indicating the direct action of GnRH
      antagonists at the pituitary cell level. In the receptor binding studies, analog
      E displaced 125I-[D-Arg6, Pro9NHEt]-sGnRH (sGnRH-A) from crude goldfish pituitary
      membrane preparations in a dose-dependent manner.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7803607
TI  - Zinc levels in the rat fetal liver are not determined by transport across the
      placental microvillar membrane or the fetal liver plasma membrane.
AB  - During pregnancy, zinc (Zn) levels in the rat fetal liver increase markedly. Why
      they do so or how the increase is regulated is unknown. We firstly investigated
      whether the increase occurs as a result of increased Zn transfer across the
      placenta and then tested whether the regulation occurred at the level of the
      microvillar membrane of the placenta or the fetal liver plasma membrane. Rats at
      different stages of gestation were injected with 7.5 microCi 65Zn in 100
      microliters rat serum and killed after 1 h. 65Zn levels in the fetus remained
      constant at equivalent to the amount in 50 microliters maternal plasma per fetus
      until Day 18; at this time they increased to equivalent to 1.33 ml and then
      continued to increase until term. We isolated placental microvillar vesicles from
      placentas at each stage of gestation, characterized them, and measured Zn uptake.
      Zn uptake rates did not change during pregnancy. Similarly, we isolated vesicles
      from fetal liver plasma membrane and measured Zn uptake. Again, the uptake
      properties did not change during pregnancy. The data suggest that some other step
      in the transport process is rate limiting and that the increase in Zn levels in
      the fetal liver that occurs during pregnancy is possibly a result, rather than a
      cause, of metallothionein induction.

PMID- 7803608
TI  - Dissociation of the reproductive and prolactin photoperiodic responses in male
      golden hamsters.
AB  - The response of prolactin (PRL) and that of the pituitary-testicular axis to
      inhibitory photoperiods were compared in immature and young adult hamsters. In
      the first experiment, 14-day-old hamsters were transferred from 14L:10D to
      12L:12D or 8L:16D. At 21, 28, 35, and 49 days of age, body weights, testes
      weights, and plasma LH were similar in all groups. In contrast, the levels of PRL
      were lower in animals on 8L:16D or 12L:12D than in those on 14L:10D and 49 days
      of age. In a second experiment, 80-day-old hamsters were transferred from 14L:10D
      to either 12L:12D or 8L:16D. At 5-wk intervals, they were weighed and bled by
      cardiocentesis and the length of the testes was measured. Photoperiods of 12L:12D
      and 8L:16D induced testicular regression, which was complete by 15 wk.
      Thereafter, augmented levels of FSH preceded spontaneous recrudescence of the
      testes in animals on both photoperiods. Serum PRL levels were significantly
      depressed within 5 wk after transfer to either 8L:16D or 12L:12D. After 15 wk as
      the testes were increasing in size in both groups, circulating PRL levels
      increased in animals exposed to 8L:16D, whereas in animals exposed to 12L:12D,
      PRL remained at or below the sensitivity of the assay. In a final experiment, on
      the day before parturition, pregnant hamsters were transferred to either 6L:18D,
      6L:30D, 6L:42D, or 6L:54D or were held on 14L:10D. There were no differences in
      testicular weights, plasma LH, or plasma thyroxine (T4) of the pups from these
      dams at 21, 36, or 48 days of age.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7803609
TI  - Chromosome mosaicism in human embryos.
AB  - In the human, mosaicism may occur before implantation; but, to determine when it
      first occurs, it is necessary to study the chromosomal complement of all
      blastomeres. Full karyotypes of blastomeres from 2- to 8-cell human embryos by
      conventional karyotyping of metaphase spreads are difficult to obtain. The aim of
      this study was to assess the stage at which mosaicism occurred in preimplantation
      human embryos through use of fluorescence in situ hybridization (FISH) with
      multiple probes. All or most blastomeres from 2- to 12-cell human embryos were
      analyzed by FISH using probes for gonosomes and chromosome 18. FISH was performed
      on blastomeres from 117 morphologically normal monospermic embryos that were not
      transferred after preimplantation diagnosis because of their risk of carrying X
      linked disease; 20 (17.1%) of these embryos were mosaic. Another group of 163
      arrested or morphologically abnormal monospermic embryos were also analyzed by
      FISH; 47 (28.8%) of these embryos were mosaic. In addition, 37 dispermic embryos
      were analyzed, and 28 (75.7%) of these were found to be mosaic. Mosaicism first
      occurred at the second cleavage division when the monospermic embryo was mostly
      diploid and at the first cleavage division when the embryo was mostly haploid,
      polyploid, or dispermic.

PMID- 7803610
TI  - Steady-state concentrations of messenger ribonucleic acid encoding cytochrome
      P450 side-chain cleavage and 3 beta-hydroxysteroid dehydrogenase/delta 5,delta 4
      isomerase in ovine corpora lutea during the estrous cycle.
AB  - The objective of these experiments was to determine the pattern of mRNA
      expression for cytochrome P450 side-chain cleavage (P450scc) and 3 beta
      hydroxysteroid dehydrogenase/delta 5,delta 4 isomerase (3 beta-HSD) during
      luteinization of the follicle and in ovine luteal tissue on Days 3, 6, 9, 12, and
      15 of the estrous cycle. Mean concentration of mRNA for P450scc was not different
      in follicles collected 4 or 24 h after the onset of estrus but increased (p <
      0.05) 3-fold by 48 h (corpus hemorrhagicum). With the methods used, mRNA for 3
      beta-HSD was not detected until after ovulation and formation of the corpus
      hemorrhagicum (48 h after onset of estrus). In luteal tissue, mean concentration
      of mRNA for P450scc increased from Days 3 to 9 (p < 0.05) and had decreased (p <
      0.05) by Day 15. Mean concentration of mRNA for P450scc was higher (p < 0.05) in
      small luteal cells on Day 9 than on Day 15, with values on Days 6 and 12 being
      intermediate. In large luteal cells, mean concentrations of P450scc mRNA
      increased (p < 0.05) between Days 6 and 12 and then decreased (p < 0.05) on Day
      15. Mean concentration of mRNA for 3 beta-HSD was not different (p = 0.33) in
      luteal tissue on any day examined. In small luteal cells, mean concentrations of
      mRNA for 3 beta-HSD decreased between Days 6 and 15 (p < 0.05) while in large
      luteal cells, mean concentrations decreased (p < 0.05) between Days 12 and
      15.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7803611
TI  - Treatment of sperm-injected human oocytes with Ca2+ ionophore supports the
      development of Ca2+ oscillations.
AB  - Oscillations of intracellular free Ca2+ concentration are an essential component
      of the oocyte response to the fertilizing spermatozoon. Ca2+ oscillations have
      also been observed in human oocytes fertilized by intracytoplasmic sperm
      injection (ICSI), but only after a considerable delay. The present study was
      performed to determine whether or not the development of Ca2+ oscillations in
      sperm-injected oocytes is influenced by exposure of the oocytes to Ca2+
      ionophore. The treatment (5 min) of sperm-injected, but not sham-injected,
      oocytes with 10 microM ionophore A23187 augmented significantly the percentage of
      oocytes that developed Ca2+ oscillations and accelerated the onset of the
      oscillations as compared to the values for solvent-treated controls. However, the
      oscillations developed only after a lag period, which ranged between 25 min and
      88 min after the removal of ionophore, during which intracellular Ca2+ levels
      returned nearly to the basal value. Each of the subsequent periodic Ca2+ rises
      was initiated from a focus in the oocyte cortex and spread throughout the ooplasm
      as a Ca2+ wave. These data suggest that ionophore treatment supports the
      physiological pattern of oocyte activation when applied after ICSI. This effect
      is probably indirect, implying the stimulation of an unknown process continuing
      during the lag period.

PMID- 7803612
TI  - Effect of vomeronasal organ removal on behavioral estrus and mating latency in
      female meadow voles (Microtus pennsylvanicus).
AB  - The vomeronasal organ (VNO) mediates the induction of behavioral estrus in
      prairie voles by male chemosignals; however, the importance of this system for
      the initiation of estrus in meadow voles, a species in which spontaneous estrus
      has been postulated, is unknown. This experiment was designed to investigate the
      influence of VNO-mediated chemosensory information on behavioral estrus in meadow
      voles housed in photoperiods simulating summer (long photoperiods; 14L:10D) and
      winter (short photoperiods; 10L:14D). The VNO was removed from nulliparous female
      meadow voles, and the percentage of animals mating after removal and the timing
      of mating onset were assessed. Removal of the organ did not suppress mating or
      change the timing of mating onset in females housed in short photoperiods. In
      animals housed in long photoperiods, in contrast, removal of the organ
      significantly increased the percentage of females mating and the percentage of
      females mating rapidly after pairing. The results indicate that chemosensory
      information mediated via the VNO is not necessary for the induction of behavioral
      estrus in meadow voles and lends support to the hypothesis that meadow voles have
      a spontaneous estrus. We postulate that polygynous, solitary meadow voles
      reproduce more effectively with spontaneous estrus than with the induced estrus
      described for monogamous, group-living prairie voles.

PMID- 7803613
TI  - Effects of temperature and restoration of osmotic equilibrium during thawing on
      the induction of plasma membrane damage in cryopreserved ram spermatozoa.
AB  - The objective of this investigation was to examine the nature of freeze/thaw
      induced plasma membrane damage in an effort to validate hypotheses about
      cryoinjury in ram spermatozoa. Spermatozoa were loaded with fluorescein diacetate
      (FDA), a marker for plasma membrane integrity, and cooled (15 degrees C/min) to
      temperatures between -10 degrees C and -30 degrees C on a cryomicroscope stage.
      Post-thaw fluorescence intensity measurements of individual cells indicated that
      freezing to temperatures between -10 degrees C and -15 degrees C did not induce
      significant membrane permeabilization. However, freezing below -15 degrees C was
      followed by membrane permeabilization immediately after thawing. A majority (>
      60%) of flagellar plasma membranes of cells frozen to -10 degrees C remained
      ultrastructurally intact during thawing; principal-piece membranes were more
      robust than middle piece membranes (p = 0.001). Significant middle-piece membrane
      breakage was, however, induced as the post-thaw temperature increased from +10
      degrees C to +30 degrees C (10 degrees C, 64 +/- 12.3% intact membranes [mean +/-
      SEM]; 30 degrees C, 43 +/- 12.5% intact membranes [mean +/- SEM]; p = 0.0085).
      Cells frozen to -30 degrees C did not exhibit this thawing effect, although the
      distinction between middle-piece and principal-piece plasma membranes was evident
      (p = 0.002). All sperm head plasma membranes were damaged by freezing and thawing
      to any combination of temperatures. Although acrosomes became swollen after
      freezing and thawing, the incidence of outer acrosomal membrane vesiculation
      remained at control (unfrozen) levels with all treatments used. Experimental
      exposure to the hyperosmotic conditions generated during freezing induced little
      flagellar membrane permeabilization, but significant damage was caused by
      restoration of osmotic equilibrium. It is suggested that membranes are initially
      destabilized during the freezing process, both by low temperature effects and by
      exposure to high salt concentrations. The resultant post-thaw degeneration of the
      plasma membrane is caused by a combination of temperature and osmotic effects.

PMID- 7803615
TI  - Developmental competence of domestic cat embryos fertilized in vivo versus in
      vitro.
AB  - Development of in vitro-fertilized (IVF) cat embryos was compared to that of
      naturally produced cat embryos in vivo and in vitro. To obtain in vivo-fertilized
      embryos, queens were mated three times daily on the second and third days of
      natural estrus and ovariohysterectomized at 64, 76, 100, 124, or 148 h after the
      first copulation. Embryos were flushed from the reproductive tract, evaluated for
      developmental stage, and cultured. For IVF, oocytes from gonadotropin-stimulated
      queens were inseminated with electroejaculated cat sperm in Ham's F-10 and
      evaluated for fertilization (cleavage to > or = 2 cells) at 30 h. In vitro
      development of embryos fertilized in vivo (n = 109) and in vitro (n = 46) was
      evaluated every 24 h for up to 10 days. High-quality embryos recovered at 64, 76,
      100, 124, and 148 h after the first copulation were typically 1 to 2 cells (13 of
      20), 5 to 8 cells (18 of 28), 9 to 16 cells (14 of 24), morulae (15 of 21), and
      compact morulae (11 of 18), respectively, suggesting blastomere cleavage once per
      day in vivo after the first three rapid cell divisions. A similar developmental
      rate to the morula stage (p > or = 0.05) was achieved in vitro by embryos derived
      from both in vitro and in vivo fertilization. Additionally, the proportion (p >
      or = 0.05) of in vivo-generated embryos (2 to 16 cells) that developed to morulae
      (64 of 83; 77.1%) was similar to that of IVF embryos (28 of 46; 60.9%). However,
      none of the IVF embryos (0/46), but 70.6% (77 of 109) of the in vivo-produced
      embryos, achieved blastocyst formation in culture (p < or = 0.05). Furthermore,
      66.2% (51 of 77) of these blastocysts exhibited zona hatching. Incidence of
      morula and blastocyst formation in the in vivo group was influenced by stage of
      the embryo at collection. Embryos that were at the 9- to 16-cell stage at
      recovery were more likely (p < or = 0.05) to achieve morula or blastocyst status
      and emerge from the zona pellucida than younger-stage counterparts. In summary,
      the in vivo and in vitro growth rate of cat embryos produced after natural mating
      was comparable to that of embryos fertilized and cultured in vitro. However,
      developmental ability to the blastocyst stage was superior for embryos produced
      in vivo after natural mating.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7803614
TI  - A 60-bp core promoter sequence of murine lactate dehydrogenase C is sufficient to
      direct testis-specific transcription in vitro.
AB  - A clone containing the 5' flanking region of the testis-specific murine lactate
      dehydrogenase C (Ldhc) gene was isolated from a mouse genomic library. Promoter
      activity was demonstrated within a 720-bp fragment in testis nuclear extract
      (TN). Interestingly, the addition of liver nuclear extract (LN) significantly
      repressed Ldhc promoter activity in the transcription assay system. Sequence
      analysis of this promoter region revealed several ubiquitous cis-regulatory
      elements, including one TATA box, one GC box, and two putative CCAAT elements.
      Analysis of a series of deletion mutants revealed that a 60-bp core promoter
      sequence was sufficient to direct basal, testis-specific transcription in an in
      vitro transcription system. A 103-kDa protein in TN and a 65-kDa protein in LN
      bind to the same palindromic sequences within the 60-bp core promoter region.

PMID- 7803616
TI  - In vivo embryogenesis, embryo migration, and embryonic mortality in the domestic
      cat.
AB  - In vivo embryogenesis, embryo migration, and survival were studied in the
      domestic cat. Queens were naturally mated (three times daily) on the second and
      third days of behavioral estrus and, if ovulation occurred, ovariohysterectomized
      at 64 (n = 8), 76 (n = 11), 100 (n = 8), 124 (n = 7), 148 (n = 6), and 480 h (n =
      8) after first copulation. Of 52 cats mated, 48 (92.3%) ovulated (as evidenced by
      the presence of ovarian CL), and of these, 38 (79.2%) either produced good
      quality embryos or had implantation sites. From the remaining cats, only
      unfertilized oocytes (n = 5), degenerating embryos (n = 4), or no oocytes/embryos
      (n = 1) were recovered. Embryos at 64, 76, 100, and 124 h after the first
      copulation typically were 1 to 4 cells (17 of 20; 85.0%), 5 to 8 cells (18 of 28;
      64.3%), 9 to 16 cells (14 of 24; 58.3%), and morulae (15 of 21; 71.4%),
      respectively; all were within the oviducts. At 148 h, embryos primarily were
      compact morulae or early blastocysts (15 of 18; 83.3%), and all were within the
      uterus. For the preimplantation groups, the overall recovery of embryos plus
      oocytes per CL was 80.6%, and the mean (+/- SEM) numbers of CL and embryos were
      64 h, 4.8 +/- 0.3, 3.1 +/- 0.8; 76 h, 4.7 +/- 0.3, 3.9 +/- 0.6; 100 h, 5.8 +/-
      0.5, 3.3 +/- 0.8; 124 h, 4.4 +/- 0.5, 4.0 +/- 0.6; and 148 h, 6.5 +/- 1.1, 3.7 +/
      0.7, respectively. Cats in the 480-h group produced a mean of 5.6 +/- 0.5 CL and
      3.9 +/- 0.5 implantation sites. In six of eight cats in this group, there was a
      disparity between CL number on a given ovary and number of implantation sites in
      the ipsilateral horn, supporting the concept of transuterine embryo migration. In
      summary, results indicated that 1) more than 90% of cats ovulated following this
      multiple mating regimen, but approximately 21% of these failed to produce any
      fertilized or viable embryos; 2) embryo developmental rate in vivo was biphasic,
      with a rapid cleavage rate to the 5- to 8-cell stage followed by a slower
      cleavage rate to the morula stage; 3) cat embryos entered the uterus as compact
      morulae or early blastocysts approximately 5.5 days after the first copulation;
      and 4) on the basis of implantation/CL ratio, approximately 30% of all ovulated
      cat oocytes underwent either fertilization failure or preimplantation embryonic
      mortality.

PMID- 7803617
TI  - Steroidogenic cytochrome P450 enzyme messenger ribonucleic acids and follicular
      fluid steroids in individual follicles during preovulatory maturation in the pig.
AB  - Changes in follicular concentrations of steroidogenic cytochrome P450 enzyme
      mRNAs were determined during preovulatory maturation. RNA was isolated from 59
      individual follicles dissected from 18 pigs during altrenogest-synchronized
      preovulatory follicular maturation: at Day 1 (pre-follicular phase), Day 3 (early
      follicular phase), Day 5 (mid-follicular phase), and Day 7 (late follicular
      phase, 24-36 h after the onset of the LH surge). Follicular fluid was aspirated
      for steroid RIA. RNA was also isolated from pooled granulosa cells, theca tissue,
      and luteal tissue. RNA was analyzed by Northern and slot-blot procedures using
      cDNA probes to human aromatase cytochrome P450 (P450arom), porcine 17 alpha
      hydroxylase cytochrome P450 (P450(17) alpha), and porcine cholesterol side-chain
      cleavage cytochrome P450 (P450scc). P450arom mRNA was expressed in both granulosa
      and theca interna cells but was not detectable in luteal tissue from Day 13 of
      the estrous cycle. Follicular P450arom mRNA concentration tended to increase
      between Days 1 and 5 and decreased (p < or = 0.05) by 92% between Days 5 and 7.
      Follicular fluid estradiol-17 beta concentration increased 17-fold between Days 1
      and 5 and then decreased (p < or = 0.05) by 96% between Days 5 and 7. P450(17)
      alpha mRNA was present in theca interna but was not detected in granulosa cells
      or luteal tissue. Follicular P450(17) alpha mRNA concentrations did not differ
      significantly among days, but the content per follicle increased (p < 0.05)
      between Days 1 and 5 and decreased (p < 0.05) between Days 5 and 7.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7803618
TI  - Luteotropic effects of follicle-stimulating hormone (FSH): II. FSH luteinizing
      hormone, and prolactin effects on second messenger systems in the corpus luteum
      of the pregnant hamster.
AB  - We have recently shown that FSH, LH, and prolactin (PRL)--alone or combined--act
      as luteotropins when incubated with luteal cells from pregnant hamsters (Yuan and
      Greenwald, Biol Reprod 1994; 51:43-49). The purpose of the present study was to
      determine which second messenger systems are affected by these hormones with
      progesterone (P4) synthesis as the principal endpoint after 4 h of incubation
      with 100,000 luteal cells. Luteal cells on Days 4, 10, or 12 of pregnancy were
      incubated with the following reagents: 10 ng of recombinant human FSH (r-hFSH),
      ovine (o) FSH, oLH, oPRL, forskolin, db-cAMP, protein kinase A inhibitor (PKI),
      protein kinase C activator (phorbol 12-myristate 13-acetate; PMA), or various
      combinations of the reagents. Forskolin and db-cAMP each stimulated P4 in a dose
      dependent manner, while PKI significantly inhibited forskolin-, r-hFSH-, oFSH-,
      and oLH-stimulated P4 on Day 4 of pregnancy. PMA (0.001-1.0 microM) did not
      affect basal P4 on Day 4, 10, or 12 of pregnancy; however, 100 nM PMA inhibited
      db-cAMP-, forskolin-, oFSH-, and oLH-stimulated P4 synthesis on Days 4 and 12.
      The antagonistic effects of PMA were reversed in all cases by concurrent
      incubation with a PKC inhibitor, H-7. On Day 4 of pregnancy, P4 was stimulated by
      oFSH and oLH with the highest levels observed in medium stimulated by the
      luteotropic complex of oFSH, oLH, and oPRL. Recombinant hFSH enhanced P4
      production in a dose-dependent manner; doses of 10 ng and above resulted in
      statistically significant differences from the control values (p <
      0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7803619
TI  - Regulation of prostaglandin synthesis by interleukin-1 beta in cultured bovine
      luteal cells.
AB  - Prostaglandins produced within the CL may serve as local modulators of CL
      function. The present study was designed to characterize the cellular mechanisms
      by which the cytokine interleukin-1 beta (IL-1 beta) stimulates prostaglandin
      production in cultured luteal cells. Cycloheximide (CHX) and actinomycin D (Act
      D) did not affect basal, but completely inhibited IL-1 beta-stimulated
      prostaglandin F2 alpha (PGF2 alpha) production (p < 0.05). The phospholipase A2
      (PLA2) inhibitor, aristolochic acid (PLA2X), and the phospholipase C (PLC)
      inhibitor, compound 48/80 (PLCX), suppressed IL-1 beta-stimulated (p < 0.05), but
      not basal, PGF2 alpha production. The addition of exogenous arachidonic acid (AA)
      restored the stimulatory effect of IL-1 beta in PLCX-treated, but not in PLA2X
      treated, cells, suggesting that PLA2 is a key regulatory point of IL-1 beta
      action. Chronic exposure of the luteal cells to IL-1 beta resulted in stimulatory
      effects beyond that of increasing AA availability, presumably by up-regulation of
      prostaglandin endoperoxide (PGH) synthase. Chronic exposure of luteal cells to IL
      1 beta also inhibited progesterone production, but this effect appeared to be
      independent of endogenous PGF2 alpha production. The ability of IL-1 beta to
      comprehensively stimulate luteal PGF2 alpha production while inhibiting luteal
      progesterone production is suggestive that IL-1 beta may facilitate regression of
      the CL.

PMID- 7803622
TI  - Abortifacient effects in the pregnant hamster of an antibody to progesterone are
      reversed by exogenous prolactin.
AB  - A single i.p. injection of 10 nmol of a monoclonal antibody to progesterone (mAb
      P4) on Day 4 of pregnancy (day of nidation) interrupts pregnancy by Day 8 (Day 1
      = sperm-positive smear) in 75% of treated hamsters (n = 8). This correlates with
      structural and functional luteolysis, significantly (p < 0.05) reduced serum
      prolactin (PRL), and a nonsignificant trend for reduced FSH (which constitute the
      minimal luteotropic complex of the hamster), but LH is unchanged. Embryos implant
      and develop normally for a while, but by Day 8 the uterus is distended with the
      resorbing products of conception. The abortifacient effects of passive
      immunization against progesterone are reversed 100% by s.c. injection of 100
      micrograms PRL daily on Days 4-7; deferring PRL treatment until Days 6-7
      maintained pregnancy in 75% of the animals, still significantly different from
      the untreated mAb-P4 group. Injection of 50 micrograms PRL on Days 4-7 maintains
      pregnancy in 50% of the mAb-P4-treated hamsters (not significantly different),
      whereas 10 micrograms PRL on Days 4-7 is wholly ineffective. No dose of FSH (0.1
      10.0 micrograms) or LH (0.4-2.0 micrograms) on Days 4-7 reversed the effects of
      mAb-P4; neither did 10 micrograms PRL plus 0.4 or 2 micrograms of FSH. The
      maintenance of pregnancy after 100 micrograms PRL on Days 4-7 is associated with
      normal serum levels of PRL, FSH, and LH and no change in the serum concentration
      of the mAb-P4 antibody.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7803621
TI  - Connexin messenger ribonucleic acids in the ovary of Atlantic croaker: molecular
      cloning and characterization, hormonal control, and correlation with appearance
      of oocyte maturational competence.
AB  - Intercellular gap junction channels are composed of connexin (Cx) protein. In the
      Atlantic croaker ovary, gonadotropin (GtH)-induced oocyte maturational competence
      is accompanied by an obligatory synthesis of RNA and protein and by the formation
      of granulosa cell-oocyte gap junctions. However, the GtH control of Cx gene
      expression in relation to follicular differentiation (including maturational
      competence) has not been examined in Atlantic croaker or in any other vertebrate
      species. Moreover, Cx genes and their products have not been characterized in
      fishes. Therefore, the objectives of this study were to characterize ovarian Cx
      mRNAs in Atlantic croaker and to determine their regulation by GtH during the
      acquisition of maturational competence. Polymerase chain reaction was used to
      amplify Cx cDNA prepared from maturationally incompetent or competent ovaries.
      Mixed primers for this reaction were based on the high sequence homology of
      selected regions of known connexins. One major fragment (Cx1) was amplified from
      incompetent ovary cDNA, and two major fragments (Cx1' and Cx2) from competent
      ovary cDNA. Sequence analysis showed that Cx1 and Cx1' are identical and that Cx1
      and Cx2 have high sequence homology to other Cx cDNAs. A cDNA library made from
      competent ovaries was screened with Cx1 or Cx2 used as probes. Two cDNAs were
      isolated: one (Cx1) encoded 282 amino acids (32,693 daltons; Cx32.7), and the
      other (Cx2) encoded 285 amino acids (32,169 daltons; Cx32.2). Both amino acid
      sequences showed all key features of Cx. Northern blot analysis showed a
      negligible level of Cx32.2 mRNA in incompetent ovaries, but a substantial rise in
      its levels accompanied the GtH induction of maturational competence. However,
      Cx32.7 mRNA levels in incompetent and competent ovaries were similar. In
      conclusion, selective activation of the ovarian Cx32.2 gene by GtH seems to occur
      during the acquisition of oocyte maturational competence.

PMID- 7803620
TI  - Estrogen production by bovine binucleate and mononucleate trophoblastic cells in
      vitro.
AB  - The bovine placenta has long been known as a source of steroid hormones. We
      performed three experiments to compare production of estrogens by bovine
      mononucleate and binucleate trophoblastic cells and examined effects of cortisol,
      progesterone, pregnenolone, testosterone, and androstenedione. In the first
      experiment, binucleate trophoblastic cells were purified by unit gravity
      sedimentation from six enzymatically dispersed placentas between 150 and 180 days
      of gestation. Cells (8 x 10(5)/ml) were incubated first at 37 degrees C for 6 h
      with Medium 199 alone (M199/6h) or with 10(-7) M cortisol (cortisol/6h). Medium
      then was replaced with 10(-7) M progesterone, 10(-7) M pregnenolone, 10(-7) M
      testosterone, or M199, and a second incubation was conducted for 4 h. Estradiol
      production did not differ between cells incubated for the first 6 h in M199 vs.
      cortisol and was not affected by progesterone or pregnenolone. Testosterone
      increased (p < 0.05) estradiol production. Estrone production did not differ
      between cells incubated for the first 6 h in M199 vs. cortisol; estrone
      production was not affected by either progesterone, pregnenolone, or
      testosterone. Mononucleate as well as binucleate cells were purified from
      placentas between 165 and 180 days of gestation and used in two other
      experiments. In the first of these, enriched populations of binucleate and
      mononucleate cells were incubated first for 6 h with Medium 199 (M199) or 10(-7)
      M cortisol. Medium then was replaced with 10(-7) M testosterone, 10(-7) M
      androstenedione, or M199 and incubation continued for 4 h.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7803623
TI  - NKR-P1+ cells in the rat uterus: granulated metrial gland cells are of the
      natural killer cell lineage.
AB  - An intriguing component of the maternal response to pregnancy is the
      differentiation of large numbers of large granular lymphocytes, termed granulated
      metrial gland (GMG) cells, in the decidua and then in the metrial gland, a
      structure in the mesometrial triangle unique to rodent pregnancy. We have used
      the monoclonal antibody 3.2.3 to NKR-P1, a surface molecule involved in
      triggering natural killer (NK) cells for lysis, to determine the numbers and
      distribution of NK cells in the nonpregnant rat uterus and during the dramatic
      changes at implant sites during pregnancy. NKR-P1+ cells were abundant in the
      nonpregnant uterus, especially in the endometrium. These cells also expressed
      CD8, CD2, and AsialoGM1. In the subepithelial stroma, the numbers were greatest
      during proestrus and estrus; in ovariectomized animals, they were severely
      decreased, but returned to normal with estrogen supplementation. At the time of
      blastocyst attachment (Day 6), NKR-P1+ cells were few around the implant and in
      the decidualizing stroma. However, on Day 8, substantial numbers were present in
      the mesometrial decidua only, and many of these cells expressed the cytolytic
      protein perforin. By Day 10, NKR-P1+ cells were common within the inner muscle at
      the base of the mesometrial triangle and in the developing metrial gland, often
      containing perforin. Larger numbers of perforin+ cells were present in the
      central decidua towards the ectoplacental cone, and many were weakly NKR-P1+
      only. On Day 12, NKR-P1+ cells were almost completely restricted to the metrial
      gland, with few in decidua, and many were weakly positive. Substantially more
      perforin-containing cells were seen, indicating that many had lost detectable NKR
      P1. This distribution pattern from Days 6-12 is similar to that described for GMG
      cells and demonstrates that in the rat they belong to the NK cell lineage. These
      cells were also CD8+ and AsialoGM1+ but negative for CD2 and class II
      histocompatibility antigens, which is very different from interleukin-2-activated
      NK cells which they resemble morphologically. The loss during differentiation of
      NKR-P1 and CD2, which are involved in target adhesion and triggering of NK cells,
      is consistent with the poor cytolytic capacity reported for these cells.

PMID- 7803624
TI  - Vascular endothelial growth factor receptor localization and activation in human
      trophoblast and choriocarcinoma cells.
AB  - Vascular endothelial growth factor (VEGF; also known as vascular permeability
      factor) is a secreted angiogenic growth factor. It is highly specific for
      endothelial cells, and its receptor, the fms-like tyrosine kinase (flt), has been
      localized only to endothelial cells in vivo. Here we describe the expression of
      mRNA encoding flt in human trophoblast as revealed by in situ hybridization. This
      mRNA is highly expressed in the cytotrophoblast shell and columns and also highly
      expressed by the extravillous trophoblast (EVT) in the maternal decidua both in
      the first trimester and at term. The trophoblast-like choriocarcinoma cell line
      BeWo also expresses this receptor and the related receptor, kinase domain
      containing receptor (KDR), which is also a receptor for VEGF. Treatment of the
      cell line BeWo with VEGF165 stimulated 3H-thymidine incorporation and tyrosine
      phosphorylation of MAP (mitogen-activated protein) kinase in a time- and dose
      dependent fashion. This study is the first demonstration of the presence of flt
      on non-endothelial cells in vivo and suggests a role for VEGF in the growth and
      differentiation of cytotrophoblast at implantation.

PMID- 7803625
TI  - Size, number, cellular proliferation, and atresia of gonadotropin-induced
      follicles in ewes.
AB  - To determine the effect of exogenous gonadotropin on size, number, cellular
      proliferation, and atresia of follicles, ewes (n = 3-5/treatment/day) received an
      injection of vehicle or FSH-P (a pituitary extract) twice daily on Days 13, 14,
      and 15 (5, 4, and 3 mg FSH-P/injection, respectively; Day 0 = estrus) and were
      slaughtered on Days 14, 15, or 16 (i.e., after 24, 48, or 72 h of FSH-P
      treatment, respectively). An additional group of ewes (Day 13 control) received
      no treatment and were slaughtered on Day 13. All ewes received an i.v. injection
      of bromodeoxyuridine (BrdU, a thymidine analog; 5 mg/kg-1 BW) 1 h before
      slaughter. For both ovaries from each ewe, number and surface diameter of all
      visible follicles were recorded, and antral follicles were classified as small (<
      or = 3 mm), medium (> 3 mm to < or = 6 mm), or large (> 6 mm). To evaluate rate
      of proliferation of follicular cells, ovaries were fixed by perfusion with
      Carnoy's solution, and BrdU was immunolocalized in paraffin-embedded sections by
      use of a specific primary antibody and indirect immunoperoxidase detection. As an
      index of the rate of cellular proliferation, labeling index (LI: number of BrdU
      labeled nuclei expressed as a percentage of total nuclei) of granulosa and thecal
      cells was determined by image analysis of antral follicles of known diameter.
      Follicular status (atretic vs. nonatretic) also was evaluated morphologically by
      using the histological sections. After 24 h of treatment (i.e., on Day 14), FSH-P
      treated ewes had an increased (p < 0.01) number of medium follicles compared with
      vehicle-treated ewes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7803626
TI  - Messenger ribonucleic acid of rat testicular retinoic acid receptors:
      developmental pattern, cellular distribution, and testosterone effect.
AB  - In order to understand the physiological importance and molecular mechanisms of
      retinoic acid regulation of spermatogenesis, we examined the ontogeny of the
      steady-state level of the mRNAs of retinoic acid receptor (RAR) alpha and gamma
      in testes; we also used Northern blot cDNA hybridization to examine the
      distribution of RAR alpha and RAR gamma in spermatogenic cells isolated from 60
      day-old rats. In addition, we investigated the effects of exogenous testosterone
      on the steady-state levels of mRNA of RAR alpha and gamma in testes of 20-day-old
      rats. The steady-state levels of both the 3.4- and 2.7-kb mRNA transcripts of RAR
      alpha in rat testes remained relatively unchanged until 20-21 days of age, then
      declined thereafter. Comparison of the relative abundance of the RAR alpha
      transcripts in Sertoli cells isolated from 20-day-old rats with that found in
      mixed spermatogenic cells isolated from 40-day-old rats suggests that both the
      3.4- and the 2.7-kb transcripts were expressed more abundantly in Sertoli cells.
      Whereas young and pachytene spermatocytes, as well as young and elongated
      spermatids, all contained the 3.4-kb transcript of RAR alpha, only trace amounts
      of the 2.7-kb transcript was detected in spermatogenic cells. In addition, trace
      amounts of a smaller transcript of RAR alpha (1.8 kb) was detected in both
      Sertoli cells and spermatogenic cells, and two larger transcripts (4.0 and 7.0
      kb) were detected exclusively in spermatogenic cells. In contrast, a single 3.4
      kb mRNA transcript of RAR gamma was detected in rat testes.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7803627
TI  - Mechanisms regulating male sexual behavior in the rat: role of 3 alpha- and 3
      beta-androstanediols.
AB  - To assess whether naturally occurring 5 alpha-androstanediols (5 alpha-androstane
      3 alpha, 17 beta-diol and 5 alpha-androstane-3 beta, 17 beta-diol) play a role in
      the regulation of male sexual behavior in the rat, their capability to restore
      copulatory behavior in castrated animals was evaluated. Androstanediols were
      chronically administered either alone or in combination with 5 alpha
      dihydrotestosterone (DHT) or with estradiol-17 beta (E2). Animals treated with
      testosterone (T), DHT, E2, and vehicle, either alone or in different
      combinations, served as controls. The occurrence of mounting, intromission, and
      ejaculation as well as detailed parameters of copulatory behavior were recorded
      twice per week for 3 weeks. At the end of treatments, the weights of sex
      accessory organs were also recorded. When 3 beta, 5 alpha-androstanediol (3 beta
      diol; 500 micrograms/day) was administered in combination with DHT (300
      micrograms/day), full copulatory behavior was restored in all subjects in a
      manner similar to that obtained with E2 plus DHT or T plus DHT combinations, thus
      indicating an estrogen-like behavioral effect of 3 beta-diol. Administration of 3
      alpha, 5 alpha-androstanediol (3 alpha-diol; 500 micrograms/day) combined with
      DHT also restored sexual behavior, though to a lesser extent. When 3 alpha-diol
      (500 micrograms/day) was simultaneously administered with E2 (5 micrograms/day),
      the copulatory behavior of castrated animals was fully restored in a fashion
      similar to that observed after administration of DHT plus E2 and T plus E2
      combinations, indicating a potent androgen-like effect of 3 alpha-diol.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7803628
TI  - Yersinia infections: centennial of the discovery of the plague bacillus.

PMID- 7803629
TI  - Photo quiz. Oriental sore (old world cutaneous leishmaniasis).

PMID- 7803630
TI  - Predicting Mycobacterium avium complex bacteremia in patients infected with human
      immunodeficiency virus: a prospectively validated model.
AB  - In cases of advanced infection with human immunodeficiency virus, mycobacterial
      blood cultures are frequently used to diagnose disseminated infection with the
      Mycobacterium avium complex (MAC). However, no prospectively validated guidelines
      exist for the use of such cultures. In this study, a two-part model for
      predicting MAC bacteremia was developed and then validated prospectively. First,
      a CD4+ cell count of < or = 50/microL was used to predict bacteremia. Then, among
      patients with < or = 50 CD4+ cells/microL, the documentation of fever on more
      than 30 days during the preceding 3 months, a hematocrit of < 30%, or a serum
      albumin concentration of < 3.0 g/dL was used to predict bacteremia. This model
      had a sensitivity of 89% and positive and negative predictive values of 30% and
      98%, respectively, for the identification of patients with bacteremia. Had the
      model been applied to patients in this study, the number of blood cultures
      performed would have decreased by 61%, but 11% of the positive cultures would
      have been missed. In short, this model can predict MAC bacteremia and can
      potentially guide the use of mycobacterial blood cultures.

PMID- 7803631
TI  - The clinical application of prediction models in medicine--predicting
      Mycobacterium avium complex bacteremia.

PMID- 7803632
TI  - Clinically significant mucosal candidiasis resistant to fluconazole treatment in
      patients with AIDS.
AB  - Eight cases of severe mucosal candidiasis in patients with AIDS who were taking
      fluconazole at a dosage of 400-800 mg/d are described. Candida albicans alone or
      in conjunction with Torulopsis glabrata or Candida stellatoidea was isolated from
      each patient. In vitro susceptibility testing demonstrated resistance to
      fluconazole in all eight cases. All tested isolates were susceptible to
      amphotericin B, and six of eight isolates tested were susceptible to
      itraconazole. All individuals were severely immunocompromised (CD4 lymphocyte
      counts: mean, 15/mm3; range, 6-39/mm3) and had been receiving prophylaxis with
      fluconazole for a mean of only 3 months (range, 1-7 months). The occurrence of
      candidal mucositis in patients receiving high doses of fluconazole is a matter of
      concern that requires further study in regard to the causes, prevention, and
      treatment of the disease.

PMID- 7803633
TI  - Azole-resistant Candida albicans: report of two cases of resistance to
      fluconazole and review.
AB  - We report the course of oropharyngeal infection by Candida albicans that was
      refractory to treatment with fluconazole in two patients infected by the human
      immunodeficiency virus (HIV). We also review the epidemiology of C. albicans with
      decreased in vitro and in vivo susceptibility to azole antifungal agents, the
      significance of such isolates, the known mechanisms by which C. albicans may
      become less susceptible to azole antifungal agents, and the efficacy of various
      treatments for mucosal candidiasis. The occurrence in HIV-infected patients of
      mucosal candidiasis that is refractory to therapy with fluconazole and is due to
      C. albicans that demonstrates decreased in vitro susceptibility to fluconazole
      has been reported since 1990. Following the release of miconazole and
      ketoconazole in the late 1970s, C. albicans with decreased in vitro
      susceptibility to these agents was isolated from patients with chronic
      mucocutaneous candidiasis who required repeated and prolonged courses of therapy.
      Subsequently, C. albicans with decreased in vitro-susceptibility to ketoconazole,
      clotrimazole, and itraconazole has been isolated from HIV-infected patients.
      Recent reports of the sexual and nosocomial transmission of wild-type C. albicans
      indicate the possibility of future person-to-person transmission of C. albicans
      with decreased in vitro susceptibility to azole antifungal agents.

PMID- 7803634
TI  - Bacteremia due to non-typhi Salmonella: analysis of 64 cases and review.
AB  - Within a 5-year period, 64 patients were hospitalized at the Chang Gung Memorial
      Hospital of Keelung (Taiwan) with bacteremia due to non-typhi Salmonella. Fifteen
      were < 24 weeks of age, 17 were between 6 months and 5 years of age, and 32 were
      > 18 years of age. An analysis of these patients revealed several significant
      differences between pediatric and adult patients. For instance, 87.5% of the
      adults but none of the children were debilitated because of severe underlying
      disease. Mortality was high (40.6%) among adults, but no deaths were observed
      among the children. Diarrhea occurred significantly more frequently among
      children (68.7%) than among adults (15.6%), while the contrary was observed in
      regard to chills, which occurred in 31% of adults and none of the children. It is
      concluded that bacteremia due to non-typhi Salmonella presents with different
      clinical features in adults than it does in children; furthermore, in adults the
      disease can be considered life-threatening, but in children it is associated with
      a favorable prognosis.

PMID- 7803635
TI  - Candida tropicalis vertebral osteomyelitis: a late sequela of fungemia.
AB  - Two adult patients who had undergone bone marrow transplantation had transient
      fungemia due to Candida tropicalis during the posttransplantation neutropenic
      period and later (at 5 and 14 months post-transplantation) developed vertebral
      osteomyelitis due to the same organism. The courses of all adult patients who
      underwent bone marrow transplantation at our center during this time were
      reviewed for determining the frequency of this problem. Molecular typing
      techniques were used to establish the relationship between the organisms isolated
      during the initial fungemia and those causing the subsequent osteomyelitis. Only
      two of 532 adults who received transplants at our center from 1980 to 1993
      developed candidal osteomyelitis. Moreover, they are part of a subset of 13
      patients (2.4% of the total) whose cultures were positive for C. tropicalis; five
      of the 13 had fungemia. The study of fungal isolates from prior sites of
      colonization and from blood sampled during the original fungemia and of
      subsequently recovered vertebral bone isolates by means of DNA restriction
      fragment analysis (with use of standard agarose gel electrophoresis or pulsed
      field gel electrophoresis) showed that the colonizing, bloodstream, and bone
      isolates were identical in each case. Transient C. tropicalis fungemia in
      severely immunocompromised patients may cause important late infectious
      complications, including osteomyelitis. Although these initial septic events may
      appear to resolve easily, the outcome in the two cases in this report suggests
      that special treatment considerations, such as immediate removal of the central
      venous catheter and intensive treatment with amphotericin B, may be required in
      selected cases for prevention of late sequelae.

PMID- 7803636
TI  - Bacteremia involving the "Streptococcus milleri" group: analysis of 19 cases.
AB  - During a 3-year study period, 19 patients at the University Hospital of
      Maastricht developed bloodstream infections with species of the "Streptococcus
      milleri" group, for an incidence of 0.33 per 1,000 admissions. The patients'
      median age was 48 years; the male-to-female ratio was 2.8. Eleven patients
      (57.9%) had underlying diseases, among which malignancy was predominant. Local
      trauma to the mucosal barrier was an important risk factor. An associated site of
      infection was found most frequently in the abdominal and thoracic cavities (nine
      and five cases, respectively). Bacteremia was polymicrobial in four of 19
      episodes. The 20 infecting S. milleri strains were identified to the species
      level; Streptococcus anginosus was the most prevalent (16 strains). Eight strains
      carried Lancefield group C. The isolates were sensitive to most antibiotics.
      Abscess formation was documented in nine cases (47.3%); repeated drainage
      procedures were required in half of these episodes. Mortality was high (five of
      19 patients, or 26.3%).

PMID- 7803637
TI  - Successful therapy for cerebral phaeohyphomycosis due to Dactylaria gallopava in
      a liver transplant recipient.
AB  - A 68-year-old liver transplant recipient who was being treated with FK 506 and
      immunosuppressive steroid therapy was admitted to our medical center because of a
      tonic-clonic seizure. Computed tomography of the head revealed multiple discrete
      cerebral abscesses, and culture of fluid drained intraoperatively yielded a
      dematiaceous fungus. The isolate was susceptible to amphotericin B and
      itraconazole but was resistant to flucytosine and fluconazole. The patient was
      successfully treated with a prolonged course of amphotericin B colloidal
      dispersion and itraconazole, as evidenced by both clinical and radiographic
      resolution of disease over a 2-year follow-up.

PMID- 7803638
TI  - Comparison of three regimens recommended by the Centers for Disease Control and
      Prevention for the treatment of women hospitalized with acute pelvic inflammatory
      disease.
AB  - This six-center, prospective, open-label clinical trial compared the efficacy and
      safety of three regimens recommended by the Centers for Disease Control and
      Prevention (CDC) for the treatment of women hospitalized for acute pelvic
      inflammatory disease (PID). The study focused on the response to inpatient
      therapy, not on long-term prevention of sequelae. A severity score was used for
      objective comparison of the degree of illness before and after therapy. Women
      were randomly assigned (in a 1:1:1 ratio) to treatment with cefoxitin plus
      doxycycline, clindamycin plus gentamicin, or cefotetan plus doxycycline. Two
      hundred seventy-five (94.2%) of 292 evaluable women required no alteration in
      therapeutic regimen. The three regimens produced almost identical cure rates. No
      serious adverse clinical or laboratory events were observed. In short, the three
      regimens recommended by the CDC for inpatient therapy of acute PID were similarly
      effective and safe.

PMID- 7803639
TI  - Clinical features and duration of traveler's diarrhea in relation to its
      etiology.
AB  - Clinical features of traveler's diarrhea (TD) were studied among 126 adult
      Finnish tourists who developed this illness during or shortly after a visit to
      Morocco. Enteric pathogens were identified in 76 (60%) of cases, whereas the
      etiology remained unidentified in 50 cases (40%). Patients with an identified
      pathogen did not differ from those with TD of unknown etiology in terms of the
      time of onset of illness or the median frequency of unformed stools in the first
      24 hours. In contrast, the median frequency of unformed stools between 24 and 48
      hours (i.e., on the second day) was 1.0 among patients with no pathogen and 2.0
      among those with enteric pathogens identified (P < .001). A similar difference
      was evident on the third day (1.0 vs. 2.5). Moreover, a lower proportion of
      patients with no pathogen identified had watery stools (28% vs. 55%). The
      durations of diarrhea and concomitant symptoms were significantly shorter and the
      recovery from TD was significantly quicker among the patients without an
      identified pathogen. Patients with one or more invasive pathogens had disease
      that was clearly more severe than that of patients with no pathogen identified;
      the difference in severity of disease was less marked for patients with invasive
      vs. noninvasive pathogens. Individuals with diarrhea due to Campylobacter species
      tended to have the most severe disease, whereas diarrhea caused by
      enterotoxigenic Escherichia coli seemed milder than that caused by other agents.
      Unfortunately, the clinician has only a limited opportunity to predict the
      etiology of TD and thus to assess the need for antimicrobial therapy at the onset
      of disease.

PMID- 7803640
TI  - Fungal sternal wound infection due to Curvularia lunata in a neonate with
      congenital heart disease: case report and review.
AB  - We describe a neonate with congenital heart disease in whom a sternal wound
      infection caused by the filamentous fungus Curvularia lunata developed following
      cardiac surgery. Despite their widespread distribution in the environment,
      Curvularia species rarely cause human infection. We also review the 43 cases of
      curvularia infection previously reported in the English-language literature; only
      four of these cases occurred in children. A wide spectrum of infections-
      including keratitis, cutaneous infections, sinusitis, allergic bronchopulmonary
      disease, pneumonia, chronic ambulatory peritoneal dialysis-related infections,
      endocarditis and disseminated infections--have been described. Curvularia is a
      pathogen that can cause disease in both immunocompetent and immunocompromised
      hosts, although more severe and disseminated disease occurs in patients with
      defective immune function. Surgery alone usually is successful for treating
      locally invasive disease, although a combination of medical and surgical therapy
      is necessary for treating disseminated infections.

PMID- 7803642
TI  - Pyogenic and tuberculous spondylodiskitis (vertebral osteomyelitis) in 80 adult
      patients.
AB  - Bacterial spondylodiskitis--i.e., adjacent vertebral osteomyelitis and diskitis-
      was studied in 80 adult patients. The infection was due to Mycobacterium
      tuberculosis in 31 cases (39%) and to pyogenic bacteria in 49 cases (61%). The
      latter pathogens included gram-negative bacilli in 16 cases (20%), Staphylococcus
      species in 15 (19%), Streptococcus species in 9 (11%), and Corynebacterium
      species in 1 (1%); the pathogens in the 8 remaining cases (10%) were not
      identified. Of the patients with tuberculous spondylodiskitis, 55% came from
      countries where tuberculosis is endemic (P < .001). Cases due to staphylococci
      and those due to M. tuberculosis were associated with a high frequency of
      previous active infection with those respective organisms at any site (47% and
      42%, respectively; P < .001) and with a high rate of neurological complications
      (33% and 32%, respectively; P < .001). Nine patients with pyogenic
      spondylodiskitis (18%) but only one patient with tuberculous spondylodiskitis
      (3%) had diabetes mellitus (P < .05). Blood cultures were positive in 23 (56%) of
      the 41 cases of pyogenic spondylodiskitis due to an identified bacterium.
      Discovertebral needle biopsy contributed to the bacteriologic diagnosis in 29
      (74%) of 39 cases.

PMID- 7803641
TI  - Fluconazole combined with flucytosine for treatment of cryptococcal meningitis in
      patients with AIDS.
AB  - Treatment of cryptococcal meningitis with amphotericin B or fluconazole is often
      unsuccessful; in only 35%-40% of cases do CSF cultures become negative by 10
      weeks after initiation of such therapy. We conducted a prospective, open-label
      clinical trial involving persons with AIDS to determine whether the rate of
      clinical success would improve when fluconazole (400 mg daily) was combined with
      flucytosine (150 mg/kg daily). At the conclusion of 10 weeks of therapy, 75% (95%
      confidence interval, 58%-87%) of 32 subjects' CSF cultures were negative. The
      Kaplan-Meier estimate of clinical success at 10 weeks was 63% (95% confidence
      interval, 48%-82%). The median time to negativity of the CSF culture was 23 days.
      Toxic side effects that were sufficiently severe to lead to the withdrawal of
      flucytosine were observed in nine subjects (28%). In this pilot study of
      fluconazole combined with flucytosine, the rate of clinical success at 10 weeks
      was greater than that previously reported with regard to the use of fluconazole
      alone or amphotericin B alone.

PMID- 7803643
TI  - Lytic vertebral lesions: an unusual manifestation of AIDS-associated Kaposi's
      sarcoma.
AB  - The differential diagnosis of neovascular skin lesions in patients with AIDS
      includes Kaposi's sarcoma and bacillary angiomatosis. It has been suggested that
      the radiographic presence of lytic bone lesions in association with these skin
      lesions supports a diagnosis of bacillary angiomatosis. We present a case of
      disseminated Kaposi's sarcoma in which evidence of lytic vertebral disease was
      seen on computed tomography; the histopathologic characteristics of the osseous
      lesions are described. Findings of magnetic resonance imaging implied more
      diffuse marrow involvement. Human immunodeficiency virus-associated osseous
      manifestations of rochalimaea infection and Kaposi's sarcoma are reviewed.

PMID- 7803644
TI  - Clinical manifestations of genital infection due to Chlamydia trachomatis in
      women: differences related to serovar.
AB  - The relationship between the infecting Chlamydia trachomatis serovar and the
      clinical manifestations of genital tract infection was evaluated in a study of
      155 women attending a sexually transmitted diseases clinic; 99 women had lower
      genital tract infection and 56 had Chlamydia-associated pelvic inflammatory
      disease (PID). In the group with lower genital tract infection, women with
      serovar F differed from those with serovars of class B or C in that they
      exhibited fewer signs of cervical infection, including easily induced bleeding (P
      = .04), edema of the zone of cervical ectopy (P = .06), and colposcopic evidence
      of mucopurulent endocervical discharge (P = .007). Serovar F also produced fewer
      infections with inclusion counts of > or = 1,000 and fewer rectal infections (P =
      .04). There was no apparent association of any specific serovar with PID. Thus,
      in this population, serovar F was associated with fewer objective clinical
      manifestations of mucopurulent endocervical discharge, and the distribution of
      chlamydial serovars found in PID reflected that found in lower genital tract
      infection.

PMID- 7803645
TI  - Clinical courses of seven survivors of Clostridium septicum infection and their
      immunologic responses to alpha toxin.
AB  - Clostridium septicum bacteremia typically portends a fulminant disease associated
      with high mortality. We describe the clinical courses of seven survivors of C.
      septicum infection and their antibody responses to the alpha toxin produced by C.
      septicum. Three patients had clinical syndromes ranging from uncomplicated
      bacteremia to early typhlitis, and three patients had syndromes ranging from
      abscess to myonecrosis and septic shock. In addition, an AIDS patient who
      developed septic shock and who had extensive gas in the retroperitoneal
      musculature did not undergo surgery but survived after receiving antimicrobial
      therapy and intensive supportive care. Both immunocompetent patients with
      myonecrosis had detectable IgG to alpha toxin by immunoblot analysis. IgG to
      alpha toxin was not detected in the four immunocompetent patients who had C.
      septicum bacteremia but who did not have myonecrosis or in the AIDS patient with
      myonecrosis. Therefore, humoral responses to alpha toxin during C. septicum
      infection may be related to the host's clinical syndrome and immune status.

PMID- 7803647
TI  - Haemophilus influenzae epididymo-orchitis and bacteremia in a man infected with
      the human immunodeficiency virus.
AB  - Haemophilus influenzae is a major bacterial pathogen in patients infected with
      the human immunodeficiency virus (HIV), although most infections with this
      organism occur in the respiratory tract. We describe an adult with HIV infection
      who presented with epididymo-orchitis due to H. influenzae. Eleven prior cases of
      H. influenzae epididymo-orchitis have been published, but all of these cases
      occurred in pediatric patients. Little is known about the prevalence of
      genitourinary tract infections caused by H. influenzae among adults. H.
      influenzae is a relatively rare cause of bacteremia in adults, but the frequency
      of H. influenzae bacteremia has been increasing among the HIV-positive
      population.

PMID- 7803646
TI  - Amebic liver abscess in infancy: case report and review.
AB  - Amebic liver abscess (ALA) is uncommon in the United States and is potentially
      lethal when acquired during the first year of life. The clinical course of ALA in
      a 10-month-old infant is presented and the characteristics of 18 previously
      described cases of infants with ALA from the United States are reported; this
      infant population (including our patient) is compared with a population of adults
      with ALA. In contrast to the initial signs in adults, those in infants are
      nonspecific and include fever, hepatomegaly, anemia, and elevated levels of
      transaminases. Colitis may occur in infants, but results of examinations for ova
      or parasites are usually negative. On presentation the amebic serology for one
      third of infants with ALA is negative. The clinical course of ALA in infants is
      usually fulminant and is associated with a mortality rate of nearly 50%.

PMID- 7803648
TI  - Treatment with intralesional granulocyte instillations and interferon-gamma for a
      patient with chronic granulomatous disease and multiple hepatic abscesses.
AB  - We present the case of a 16-year-old girl with p22-deficient chronic
      granulomatous disease in whom multiple hepatic abscesses secondary to
      Staphylococcus aureus infection developed. Infection persisted despite extensive
      surgery and aggressive antibiotic therapy. Conventional intravenous granulocyte
      transfusions were not tolerated because of the development of alloantibodies to
      HLA. Treatment with interferon-gamma and intralesional granulocyte infusions was
      associated with dramatic clinical and radiographic improvement. No morbidity was
      associated with this therapy. To our knowledge, this is the first report of
      treatment with intralesional granulocyte instillations. Intralesional granulocyte
      instillation in association with interferon-gamma administration may result in
      clinical improvement in the conditions of patients with chronic granulomatous
      disease and hepatic abscesses for whom conventional therapy has failed.

PMID- 7803649
TI  - Transient exacerbation of tuberculous lymphadenitis during chemotherapy in
      patients with AIDS.
AB  - We describe three men with disseminated, drug-sensitive tuberculosis and advanced
      human immunodeficiency virus disease (CD4+ lymphocyte count, < 50/mm3) who had
      flares of tuberculous lymphadenitis with suppuration during the initial weeks of
      successful chemotherapy. Bactericidal drugs may kindle these transient
      exacerbations, which involve neutrophils but apparently do not require normal
      helper T cell function. In patients with AIDS, as in immunocompetent individuals,
      treatment-related flares of lymphadenitis are usually not an adverse sign,
      provided that drug resistance and nonadherence have been excluded.

PMID- 7803650
TI  - Clinical significance of primary vs. secondary bacteremia due to nontyphoid
      Salmonella in patients without AIDS.
AB  - We retrospectively reviewed the charts of 51 patients with primary nontyphoid
      salmonella (NTS) bacteremia who did not have AIDS and who had no history of
      gastroenteritis and no other identified source of infection. We compared these
      patients with 58 patients who developed secondary NTS bacteremia following an
      episode of gastroenteritis. The following characteristics were more frequently
      associated with primary NTS bacteremia than with secondary NTS bacteremia: age >
      60 years (51% vs. 33%; P < .05), glucocorticoid therapy (41% vs. 13%; P < .01),
      and severe immunosuppression (65% vs. 14%; P < .01). More patients with primary
      NTS bacteremia had hematologic malignancies, solid tumors, and connective-tissue
      diseases; in eight cases, primary NTS bacteremia occurred simultaneously with or
      preceded these disorders. We suggest that the possibility of severe
      immunosuppression be investigated for patients with salmonella bacteremia who
      have not had or do not have gastroenteritis.

PMID- 7803651
TI  - Lung abscess due to Streptococcus mitis: case report and review.
AB  - Streptococcus mitis is a bacterium traditionally regarded as a normal commensal
      of the oropharynx, skin, and intestinal and genital tracts. To our knowledge, we
      describe the first case of bilateral lung abscesses caused by S. mitis in an
      immunocompetent host. The abscesses were successfully treated with clindamycin
      and gentamicin. Our case illustrates that S. mitis should be considered a cause
      of pulmonary abscesses.

PMID- 7803652
TI  - Evaluation of the sensitivity of RT-23 purified protein derivative for
      determining tuberculin reactivity in a group of health care workers.
AB  - Since 1958 the World Health Organization (WHO) has recommended the use of RT-23
      (2 tuberculin unit [TU] purified protein derivative [PPD]) instead of the
      standard 5 TU PPD to establish the prevalence of tuberculosis (TB) around the
      world. Before starting a hospital program to control the transmission of TB among
      health care workers at the National Institute of Nutrition (Mexico City), we
      compared the tuberculin product commonly used in Mexico (RT-23) with that used in
      the United States (5 TU PPD). In this trial the Mantoux test was performed on 80
      health care workers from various areas of the hospital: 5 TU PPD and RT-23 were
      simultaneously inoculated in the left forearm and in the right forearm,
      respectively. The test results for both tuberculin products were read 72 hours
      later. When a 10-mm induration was used as the cutoff for reactivity, the
      specificity with use of RT-23 was 100%, but the sensitivity was only 57%.
      However, when a 5-mm induration was used as the cutoff, the sensitivity with use
      of RT-23 was 90%. Because of these findings, we advise that every country using
      RT-23 either consider changing the cutoff for reactivity or consider using 5 TU
      PPD for reassessment of the data on the incidence and prevalence of TB that were
      obtained with use of RT-23 (the product recommended by WHO).

PMID- 7803654
TI  - Mycobacterium kansasii sinusitis in a patient with AIDS.

PMID- 7803653
TI  - Paranasal sinus infection due to atypical mycobacteria in two patients with AIDS.
AB  - Atypical mycobacteria, which are common opportunistic pathogens in patients with
      AIDS, have not been previously implicated in the pathogenesis of paranasal sinus
      infections; we describe two such patients. Clinical and radiographic evidence of
      bilateral maxillary and ethmoid sinusitis was observed for one patient; his
      infection proved resistant to therapy with conventional antimicrobials and
      decongestants. Endoscopic ethmoid sinus biopsy yielded a specimen containing acid
      fast bacilli (AFB) that were later identified as Mycobacterium kansasii.
      Antimycobacterial therapy had not resulted in amelioration of the sinusitis > 2
      months later, at which time he died of cerebral toxoplasmosis. The second patient
      presented with a tender right frontotemporal soft-tissue mass; a computed
      tomogram disclosed that it extended through the frontal bone to the frontal
      sinus. Inflamed tissue debrided from the sinus contained AFB; cultures first
      yielded M. kansasii and later Mycobacterium avium complex. Bacteremia due to both
      organisms was also demonstrated. Infection progressed despite therapy.

PMID- 7803655
TI  - Paradoxical presentation of intracranial tuberculomas after chemotherapy in a
      patient with AIDS.

PMID- 7803656
TI  - Candidal sepsis and meningitis in a very-low-birth-weight infant successfully
      treated with fluconazole and flucytosine.

PMID- 7803657
TI  - Prolonged fecal excretion of verotoxin-producing Escherichia coli following
      diarrheal illness.

PMID- 7803658
TI  - Primary infection with human immunodeficiency virus that presented as Stevens
      Johnson syndrome.

PMID- 7803659
TI  - Parotitis due to Salmonella enteritidis.

PMID- 7803660
TI  - Disseminated toxoplasmosis following autologous bone marrow transplantation.

PMID- 7803661
TI  - Mycotic aortic aneurysm due to Yersinia enterocolitica.

PMID- 7803662
TI  - Coccidioidomycosis presenting as an omental mass.

PMID- 7803663
TI  - Surgical-site infection due to Streptococcus pneumoniae following laparoscopic
      cholecystectomy.

PMID- 7803664
TI  - Visceral infection due to Leishmania tropica in a veteran of Operation Desert
      Storm who presented 2 years after leaving Saudi Arabia.

PMID- 7803665
TI  - Fatal pulmonary infection caused by Corynebacterium striatum.

PMID- 7803666
TI  - Recurrent Streptococcus sanguis meningitis in a patient with a
      ventriculoperitoneal shunt.

PMID- 7803667
TI  - Detection of Bacteroides fragilis enterotoxin in the feces of a child with
      diarrhea.

PMID- 7803668
TI  - Empirical therapy for febrile, neutropenic patients: persistence of
      susceptibility of gram-negative bacilli to aminoglycoside antibiotics.

PMID- 7803669
TI  - Do bacteriuria and candiduria have predictive value in the diagnosis of
      postlaparotomy peritonitis?

PMID- 7803670
TI  - Septicemia due to non-O:1 Vibrio cholerae in a patient with AIDS.

PMID- 7803671
TI  - Staphylococcus lugdunensis as a cause of breast abscess.

PMID- 7803672
TI  - A fatal case of hemorrhagic colitis, thrombocytopenia, and renal failure
      associated with verocytotoxin-producing, non-O157 Escherichia coli.

PMID- 7803673
TI  - [Incentives in primary care. Work Group of the semFYC].

PMID- 7803674
TI  - [Health programs: responsibility of the primary health team or the health sector?
      Program or service?].

PMID- 7803675
TI  - [Effectiveness of tetanus vaccination in an adult population 10 years after the
      last dose].
AB  - OBJECTIVE: To check if antitetanus immunity after a correct vaccination lasts the
      anticipated 10 years. DESIGN: Sero-epidemiological crossover study. Determination
      of tetanus antitoxin by the ELISA method. SETTING:  SETTING: The town of Barrado
      in Caceres. PATIENTS AND OTHER PARTICIPANTS: 136 adult men and women (average age
      54.6 +/- 15.9 years; range, 24 to 87) who had received their most recent
      vaccination during a 1981-1982 campaign. 71.32% received three doses.
      MEASUREMENTS AND MAIN RESULTS: 82.35% +/- 6.40 of the sera analysed (percentage
      +/- C.I. 95%) maintained adequate levels of protection (> or = 0.01 Ui/ml). 100%
      of those under 35, revaccinated in 1980-81 because they were ELISA negative in
      spite of earlier school vaccination, were protected. The average concentrations
      did not differ significantly by gender and age-groups, although a tendency to
      decrease with age was noted. CONCLUSIONS: Anti-tetanus vaccination in the
      individuals studied provided lasting protection, detectable for 10 years in 76
      89% of cases. This level of effectiveness lends support to the criterion of
      administering back-up doses every 10 years.

PMID- 7803676
TI  - [Evaluation of the effectiveness of a physical exercise program in weight
      reduction].
AB  - OBJECTIVE: To evaluate the effectiveness of a programme of individualised
      physical exercise in reducing fat weight. DESIGN: A randomised preventive trial.
      SETTING: Health Centre. PATIENTS: Obese people of both sexes, between 32 and 67
      years old and with a fat percentage of 20-45% (men)/25-50% (women), were selected
      at random from among chronic patients at the Centre, with the exclusion of
      patients with heart diseases and of others with pathologies which made the
      programme's completion difficult. Two samples, comparable in gender, age and fat
      percentage (n1=49, n2=47), were obtained. INTERVENTIONS: THE study lasted 6
      months, with 3 evaluations. The Intervention Group (G1) was advised to walk: the
      frequency, length and intensity of the exercise was calculated individually with
      a computer programme. Measurements and main results. Weight, height and 4
      cutaneous folds were measured in each evaluation, where the Index of corporal
      mass (ICM), fat percentage and fat weight (FW) were calculated. The programme's
      acceptance was assessed according to compliance and subjective improvement. In
      the last evaluation, the GI achieved a 2.9% average decrease in the ICM, with no
      appreciable changes in the CG (p < 0.001). The FW in the GI decreased by 18%,
      whereas in the GC it increased by 12% (p < 0.001). Sixteen patients of the GI
      (32.7%) succeeded in reducing their FW by more than 20%, as against one
      individual (2.1%) of the GC (p < 0.0001). In the GI, 93.9% noted improvement in
      their physical, and 75.5% in their mental, well-being. 67.3% stated that they
      exercised more than three days a week. CONCLUSIONS: An individually tailored and
      complete prescription of exercise facilitates and improves compliance, achieving
      greater decrease in fat weight.

PMID- 7803677
TI  - [Viewpoint of the primary health care: are the new units of mental health
      useful?].
AB  - OBJECTIVES: To assess the impact on primary care of the new mental health units
      (MHU). DESIGN: Descriptive study based in a mail survey. SETTING: Primary care
      professionals of the Valencian Health Service (Autonomous Valencian Community).
      SUBJECTS: 847 professionals answered on time (45, 9, 37, 4% were general
      practitioners, pediatricians, nurses and social workers, respectively).
      MEASUREMENTS AND MAIN RESULTS: In this research were assessed the primary care
      viewpoint about activities, resources and the level of satisfaction with the
      mental health units. A 15-items survey was used. The results suggest that this
      new units have improved accessibility, treatments and communication between
      levels; waiting-time for appointment in child mental health and the number and
      distribution of resources were the worse aspects. We found a relationship between
      positive views of MHU and earlier contact with mental disorders or treatment.
      CONCLUSIONS: Primary-caregivers can do like referees to evaluate the mental
      health care. A positive image of these MHU was showed.

PMID- 7803678
TI  - [Alcohol consumption by primary care physicians].
AB  - OBJECTIVE: To find the consumption of alcoholic drinks by Primary Care doctors.
      DESIGN: A descriptive study using an anonymous questionnaire. SETTING: Health
      base areas located in the Baix Llobregat and in Barcelona city. MEASUREMENTS AND
      MAIN RESULTS: Total coverage was 68.7%. In the group which replied, daily
      consumption along with week-end consumption predominated. Men consumed alcohol
      more often and in greater quantity than women. The prevalence of excessive
      drinkers according to the PAPPS criteria was 5.9%. 29% of the doctors exceeded
      the level of alcohol consumption considered acceptable by their own criteria, no
      gender differences being appreciated. Similarly, 33% of them accepted consumption
      above that recommended by the experts. CONCLUSIONS: The consumption of alcoholic
      drinks found among Primary Care doctors was low in comparison with other studies
      of medical groups or the general population. The Primary Care doctor occupies a
      privileged position in the prevention of excessive consumption of alcoholic
      drinks, which implies that their own alcohol consumption and training could have
      an impact on carrying out preventive activities in this field.

PMID- 7803680
TI  - [Analysis of a study of the contacts of pulmonary tuberculosis patients in a
      Health Area during 1991 and 1992].
AB  - OBJECTIVE: To find whether the systematic investigation of the contacts of
      Pulmonary Tuberculosis patients is carried out. DESIGN: Crossover and
      descriptive. SETTING: Asturias Health Area VIII. PATIENTS AND OTHER PARTICIPANTS:
      We examined whether contacts of the cases of Pulmonary Tuberculosis diagnosed in
      our area during 1991 and 1992 were correctly studied, in line with the criteria
      of the American Thoracic Society (ATS). MEASUREMENTS AND MAIN RESULTS: During the
      two years there were 139 cases of Tuberculosis of all types, which supposes an
      incidence rate of 74 per 100,000 inhabitants per year. We excluded 29 of the 110
      Pulmonary Tuberculosis patients (decease, change of residence, incomplete
      personal data). We found 227 contacts of the remaining 81 (2.8 per patient). The
      initial study was complete for 133 contacts (58.5%), incomplete for 40 (17.6%)
      and was not carried out for the remaining 54 (23.7%). Only 61 (26.9%) of the
      total number of contacts were correctly studied and followed up. Only 58 contacts
      benefitted from Chemoprophylaxis. Out of the 79 cases where the repetition of the
      Mantoux test was indicated because the first was negative, it was in fact only
      repeated in 17 (21.5%). There were no significant differences between Primary and
      Secondary Care as to the study and proper follow-up of the contacts. CONCLUSIONS:
      A high incidence of Tuberculosis in our area. A deficient study and follow-up of
      contacts at all the levels of care.

PMID- 7803679
TI  - [Study of vaccination of children at a health center].
AB  - OBJECTIVE: To find the vaccination coverage of children seen at a Health Centre.
      To complete the vaccination, assess the validity of the clinical notes as a
      record and to verify the tendency for the number of those properly vaccinated to
      decrease with age. DESIGN: Crossover and descriptive. SETTING: Chopera I Primary
      Care team. PARTICIPANTS: The 877 children between 4 months and 7 years old at a
      Paediatrics clinic and between 12 and 16 years at a general medical clinic.
      MEASUREMENTS AND RESULTS: The percentage of those properly vaccinated were, for
      the first five appointments of the official vaccination calendar, 85.29%, 89.24%,
      83.98%, 81.90% and 81.95%, respectively; at 6 years, 65.51%; for German Measles,
      44.30%; and in the last one, 40.80%. The percentage of the 2 to 5-year old cohort
      fully vaccinated was 91.10%; and of the 15 to 16-year old cohort, 37%.
      CONCLUSIONS: The importance of vaccination surveys as against other measures.
      Limitations of surveys at the Health Centre. First vaccination percentages close
      to W.H.O. objectives. Decrease with age of those properly vaccinated. Need for
      universal recording systems and that the Primary Care teams assume the prime
      responsibility in vaccination monitoring.

PMID- 7803682
TI  - [Role of primary care in the treatment of problems related to alcohol
      consumption: motivation to change].

PMID- 7803681
TI  - [Non-systematic vaccines. I].

PMID- 7803683
TI  - [Treatment of gout].

PMID- 7803684
TI  - [Geriatric AIDS: a distinct epidemiological pattern].

PMID- 7803685
TI  - [Medical center study of prescriptions from the pharmacy office].

PMID- 7803686
TI  - The optimization of technological condition in the fermentation process of
      glutamate by pattern recognition method.
AB  - The technological condition in the fermentation process of fermentation glutamate
      (such as pH value, temperature, ventilation rate, etc.) were optimized by
      computerized pattern recognition method. The visible optimum region may be found
      based on the mapping from the multi-dimensional pattern space into a plane. It is
      then transformed along the reciprocal direction into the original data space
      using Monte Carlo simulation, so the orientation of optimization and the best
      combination of all parameters can be determined. A new mathematical model is
      being proposed based on the experimental evidence in production. The transfer
      ratio of glucose to glutamic acid, the production capacity and the glutamic acid
      concentration increase 2.9%, 1.45% and 2.65% respectively by operating this
      optimization method. The method has been widely extended to factories and has
      granted in decreasing the expense of raw materials and that of the production
      cost.

PMID- 7803687
TI  - Studies on high concentration ethanol fermentation of raw ground corn by
      Saccharomyces sp. H0.
AB  - In this study, high concentration alcoholic fermentation coordinated with
      saccharification from raw ground corn was performed at 30 degrees C, pH 4-5, in
      batch culture using Saccharomyces sp. H0 which was constructed by hybridization
      in this laboratory and the glucoamylase preparation produced on a large scale in
      China. The optimal conditions for high concentration ethanol production were that
      the amount of the glucoamylase preparation was 300 u/g of raw ground corn, the
      inoculum size of the yeast was 2.7 x 10(6) cells/ml, the fermentation temperature
      was 30 degrees C, the starting concentration of raw ground corn was 33.0% (w/v),
      and the fermentation period was 70 hr. At the end of fermentation, 17.5% (v/v)
      ethanol was yielded, with 0.19% reducing sugar, 3.5% total sugar and 16.0% cell
      viability remaining in the fermented mash. In the case of 36.0% (w/v) of the
      initial raw ground corn concentration, the strain could produce 18.0% (v/v)
      ethanol, leaving 0.81% reducing sugar and 5.1% total sugar in the media. We found
      that the glucoamylase preparation which is usually employed for saccharification
      of cooked starch could be used for efficient saccharification of raw ground corn
      starch.

PMID- 7803688
TI  - Preparation, characterization and application of monoclonal antibodies against
      PAI-1.
AB  - Six hybridoma cell lines (AP1-AP6) secreting monoclonal antibodies (McAb) against
      PAI-1 were obtained by fusing the murine myeloma cell line SP2/0 with the spleen
      cells from Balb/c mouse immunized with recombinant PAI-1 expressed in E. coli.
      These antibodies were purified by SPA affinity chromatography. All McAbs
      recognized rPAI-1 and PAI-1 from the human hepatoma cell line HepG2. The titers
      of ascites were more than 10(6). The antibody-antigen affinity constants (Kaff)
      for anti-PAI-1 McAb measured by EIA were between 3.45 x 10(7)-1.05 x 10(10) M.
      AP2 and AP3 McAbs were effective in quenching the activity of PAI-1. Partial
      quenching of PAI-1 activity was achieved with AP4, AP5 and AP6 McAbs
      respectively. AP1 McAb had no effect upon PAI-1 activity. Three of the six McAbs
      (AP1, AP4 and AP5) bound to the PAI-1/t-PA complex, while the others did not. The
      PAI-1 was purified 51 folds to homogeneity from serum free medium of HepG2 with
      the recovery rate of 92% by one-step procedure using Sepharose 4B conjugated with
      anti-PAI-1 McAb (AP1, AP3 and AP4). A sandwich ELISA for the measurement of PAI-1
      antigen in human plasma was developed, based on anti-PAI-1 McAb against non
      overlapping epitopes. The mean value of plasma PAI-1 for the healthy donors was
      24.7 +/- 7.75 ng/ml measured by ELISA.

PMID- 7803689
TI  - Studies on the extracellular polysaccharide from Agrobacterium radiobacter biovar
      I S-1231.
AB  - A strain S-1231 isolated from specimen of soil around Beijing area is gram
      negative, non-sporing, motile by peritrichous flagella. It produces
      exopolysaccharide succinoglycan from carbohydrates as its carbon source but not
      starch and cellulose. Acid is produced during fermentation of glucose. Growing
      for 12-24 hr, the cells are rods 0.7-0.8 x 1.3-1.5 microns, round ended, single
      or in pairs. Colonies on nutrient agar plate are unpigmented, circular, raised,
      smooth and moist-glistening, edge entire. The organism produces 3-ketolactose and
      is unable to invade sunflower tissue. The G+C content of DNA is 62.8-63.4 mol%.
      The organism is referred to as Agrobacterium radiobacter. Moreover, the strain is
      oxidase-positive, catalase-positive, H2S-produce and can grow at 35 degrees C and
      2% NaCl also. Litmus milk is alkalified. Thus, the organism was renamed
      Agrobacterium radiobacter biovar I. Component analyses showed that the
      exopolysaccharide (Agran-S) from A. radiobacter biovar I S-1231 consisted of D
      glucose (69.1%), D-galactose (8.6%), pyruvic acid (9.5%) and succinic acid
      (10.5%). Methylation analyses revealed that the polysaccharide Agran-S contained
      following main structural units: (1-->3)-linked D-glucose (21.2%), (1-->3)-linked
      D-galactose (11.4%), (1-->6)-linked D-glucose (10.5%), (1-->4)-linked D-glucose
      (30.4%), (1-->4, 1-->6)-linked D-glucose (22.2%) and terminal D-glucose (4.3%).
      The -1H-NMR spectrum of the polysaccharide indicated that the linkages in the
      polymer are all beta-glycosidic. The IR spectra of the polysaccharide revealed
      the presence of ester linkage in polysaccharide Agran-S.

PMID- 7803690
TI  - Studies on isolation and purification of penicillin acylase by adsorption on
      bentonite.
AB  - When bentonite I as an absorbent according to 0.6% (w/v) was added to the
      supernatant of the fermentation broth for adsorption of penicillin acylase from
      Bacillus megatherium, 100% activity of penicillin acylase and about 10% protein
      in the supernatant were adsorbed. The adsorption of enzyme was not obviously
      changed with different pH and salt concentration of the supernatant. Various
      kinds of buffer with different pH were used to wash the enzyme-adsorbent complex.
      Only 1% enzyme activity adsorbed was washed out; however, it can wash out about
      15% protein adsorbed. When phosphate buffer containing 10% PEG and NaCl as an
      eluent was used to elute the complex, 100% of enzyme activity adsorbed on the
      complex would be eluted, and purification and concentration times of enzyme could
      achieve about 25 and 6, respectively. The isolation and purification process can
      be carried out at room temperature. Its characters were very simple and showed a
      high recovery yield of enzyme activity, and it can be directly used for isolation
      and purification of penicillin acylase from the fermentation broth.

PMID- 7803691
TI  - Cloning of polygalacturonase (PG) cDNA and inhibition effects of its antisense
      RNA on the expression of PG gene in transgenic tomato plants.
AB  - We have amplified a 1.5-kb PG cDNA including its complete open reading frame,
      using two primers specific to PG gene and PCR technique. Its fidelity and
      correctness were confirmed by restriction mapping and partial DNA sequencing. The
      PG gene was then inserted into a binary vector, pBin437, in an inverted
      orientation between the 35S promoter with duplicated enhancers and the Nos3'
      transcriptional termination sequence, and the resulting plasmid pBPG was
      introduced into LBA 4404. The A. tumefaciens harboring pBPG was used to transform
      tomato plants. Sixty kanamycin-resistant transformants were selected. PCR
      detection showed two-third of the transformed plants tested (30 plants) contain
      the exogenous PG gene. The PG activity assay and SDS-PAGE analysis of proteins
      from ripening fruit cell wall showed that the PG activity in transgenic tomato
      plants were inhibited in different extent. One of them, plant 3, gave only 7% PG
      activity compared with the control (100%). These results suggest that the
      expression of the anti-PG gene has effectively inhibited the expression of
      endogenous PG gene. The effect of low-level PG activity on tomato fruit ripening
      and storage is being investigated.

PMID- 7803692
TI  - Coleopterancidal delta-endotoxin and constructing its genomic library.
AB  - The composition of crystal proteins and plasmid patterns in five new
      coleopterancidal strains of Bacillus thuringiensis were investigated. Larvae of
      Plagiodera versicolora were chosen as a model insect in bioassay. Strain YM-03
      had the highest toxicity. Plasmid patterns were detected by rapid agarose gel
      electrophoresis. It was demonstrated that plasmid patterns of five Bt strains
      were quite different. The partial amino acid sequences of the N-terminal of
      crystal protein from YM-03 were analyzed by amino acid analyzer. A genomic
      library of delta-endotoxin of YM-03 was constructed. The EcoRI fragments (20-30
      kb) from the total DNA were ligated with the vector DNA of pLAFRI. Thirteen
      clones which contained both of pLAFRI and foreign DNA fragments were obtained
      from 17 recombined plasmids. The frequency of recombinant clones was 76%. Three
      positive clones, LE392 (pBYM2), LE392 (pBYM3) and LE392 (pBYM4) were detected
      from 1200 resistant clones by using a synthesized 18bp probe from a
      coleopterancidal delta-endotoxin gene. It was shown that LE392 (pBYM3) and LE392
      (pBYM4) had the same EcoRI digestion patterns and that they all contained
      coleoptera-specific delta-endotoxin gene but showed a different level of
      expression.

PMID- 7803693
TI  - The glutamate biosensor and its application to flow injection analysis system.
AB  - A micro-enzyme electrode was fabricated by cross-linking L-glutamate oxidase with
      glutaraldehyde on aminopropyl-platinized platinum wire. A flow injection analysis
      system with glutamate sensor was used for L-glutamate determination. The peak
      current is linearly related to the L-glutamate concentration in the range of 0.02
      2.0 mM, with good performance, accuracy (CV = 0.4%), fast response (< 60s), and
      stability (> 20 days). The system was applied to determine the concentration of L
      glutamate in a fermentation broth. The recovery rate was in the range of 98.7
      107.5%.

PMID- 7803694
TI  - Determination of oxygen permeability and volumetric oxygen transfer rate of
      shaken flasks.
AB  - The oxygen permeability passing through the gauze layer and the actual and
      apparent volumetric oxygen transfer rate, KLa and (KLa)app, respectively, were
      determined in specially designed Erlenmeyer flasks, which have an oxygen
      electrode inserted in the middle part of flasks. The oxygen transfer rate was
      determined by sulfite oxidation. As a result, the oxygen permeability passing
      through 8 layers of gauze at 37 degrees C, 220 rpm, with 50 ml sulfite solution
      in a 500-ml flask was 43.7 mol/m.h atm; as the oxygen partial pressure decreased
      by 6.1%, the value of KLa increased by 100%; the relationship between rotational
      speed of shaker, n(rpm); volume of flask, V(ml); liquid content in flask, VL(ml);
      temperature of shaker, t(degrees C) and KLa, as well as (KLa)app (1/h) were:
      [formula: see text]

PMID- 7803695
TI  - The sequence of xylose isomerase gene from Streptomyces diastaticus No. 7 M1033.
AB  - The DNA sequence of the xylose isomerase gene from Streptomyces diastaticus No. 7
      M1033 from Hainan Province has been determined. The structure gene of the enzyme
      is composed of 1161bp, corresponding to 387 amino acid residues. The G+C content
      of the gene is 72.1%. The probability of G or C on the third position of the
      codon is 98%. At the level of amino acids, this xylose isomerase displays high
      homology with those from other Actinomycete strains, particularly those from
      Streptomyces strains.

PMID- 7803696
TI  - A stochastic model for neuronal bursting.
AB  - A new stochastic model for bursting of neuronal firing is proposed. It is based
      on stochastic diffusion and related to the first passage time problem. However,
      the model is not of renewal type. Its form and parameters are physiologically
      interpretable. Parametric and non-parametric inferential issues are discussed.

PMID- 7803697
TI  - Self-organisation of living systems towards criticality at the edge of chaos.
AB  - A principle of self-organization toward a critical state is proposed as a
      metadynamics of evolutionary processes. When the propagation velocity of
      information is slow as in living systems, discrepancy occurs between the virtual
      process and the actual one. The degree of discrepancy is defined for discrete
      dynamical systems on the scheme of perpetual disequilibration (PD), proposed by
      Gunji and others. It is supposed that adaptable systems tend to evolve so that
      the discrepancy may be minimized. A principle of the minimum degree of PD is
      applied to cellular automata and Boolean networks. These complex systems have the
      minimum degree of PD at the border between order and chaos, and thus are expected
      to evolve to the critical state at the edge of chaos. This self-organized
      criticality is a generalized form of Bak's self-organized criticality.

PMID- 7803698
TI  - Changes in sensitivities of amplitude and frequency curves of the Hodgkin-Huxley
      system produced by variations of maximal conductances.
AB  - The question of sensitivity of amplitude and frequency curves of the Hodgkin
      Huxley system to variations of maximal values of sodium (gNa) and potassium (gK)
      conductances is considered. Changes in the sensitivity produced by simultaneous
      changes in gNa and gK values are examined. It has been shown that simultaneous
      increase of the values of gNa and gK is accompanied by decrease of the
      sensitivity and, therefore, by improvement of quality of nerve fiber functioning.

PMID- 7803699
TI  - Insulin stimulation of high frequency phosphorylation dynamics in murine
      erythroleukemia cells.
AB  - The phosphorylation potentials of two proteins (M(r) 81 kDa and 63 kDa) in
      extracts of murine erythroleukemic (MEL) cells both vary in an oscillatory
      manner, sometimes changing by as much as 100-fold in 10 min. Direct analysis of
      the temporal changes indicates the existence of periodic modulation of the
      frequencies, amplitudes and mean levels of the two rhythms. In both cases,
      periodogram analyses, by two methods, confirm the presence of several
      oscillations having periods in the range 20-100 min which tend to occur in
      (pseudo) periodic bursts. Insulin has been found to enhance these oscillations in
      a manner comparable with its effect on rhythmic variations in cell morphology.
      Despite the marked similarity in the behaviour of the two proteins, no particular
      phase relationship existed between the two temporal variations, suggesting
      differences between the underlying driving forces.

PMID- 7803700
TI  - Biomolecular computing: from the brain-machine disanalogy to the brain-machine
      analogy.
AB  - The analogy between the main information features of the brain and molecular non
      discrete information processing devices based on non-linear dynamic mechanisms is
      considered. These information processing mechanisms predetermine the character of
      basic primitive operations of these devices, which seem to be capable of solving
      problems of a rather high computational complexity. Non-linear dynamic processing
      mechanisms open the way to elaboration of devices embodying, in a natural way,
      the fuzziness of information features that is typical of information processing
      inherent in soft 'humanistic' systems.

PMID- 7803701
TI  - Moiety-conserved cycles and metabolic control analysis: problems in sequestration
      and metabolic channelling.
AB  - This paper considers certain aspects of the analysis of moiety-conserved cycles
      in terms of metabolic control analysis. Two response coefficients are discussed:
      the response coefficient with respect to the total number of moles in a cycle
      (RVT), and the response coefficient with respect to perturbations to the internal
      state of a pathway (RVS). The relationship between these two different measures
      is derived and two examples are given to illustrate how the results may be used
      to simplify the analysis of particular complex pathways. One example considers
      how metabolite sequestration affects the flux summation theorem for which the
      analysis confirms the known result that sequestration can depress the value of
      the summation to below unity. The second example investigates the effect of
      metabolic channelling on the summation theorems. The analysis indicates that in
      contrast to metabolite sequestration, metabolic channelling can cause the flux
      summation theorem to exceed the value of unity. In addition, the maximum value
      that the summation theorem can reach under these conditions is shown to be equal
      to 2. Finally, this analysis indicates how one might use control analysis through
      the use of enzyme titration to determine whether metabolic channelling occurs in
      real systems or not.

PMID- 7803702
TI  - Normal and neoplastic mammary gland growth in MMTV/TGF alpha transgenic mice.
AB  - Biochemical and Dynamic change of mammary glands in different reproductive states
      were studied in comparison with histological structures in female and male
      transgenic mice bearing human transforming growth factor alpha (TGF alpha) cDNA
      under the control of the mouse mammary tumour virus enhancer/promoter. Female and
      male F1 mice between SHN female and transgenic male mice were divided into TGF
      alpha (+) and TGF alpha (-) groups according to the presence of TGF alpha gene at
      approximately 50 days of age. While there was little difference in mammary gland
      contents of DNA and RNA in females at 2 months of age, both nucleic acid contents
      were elevated markedly in TGF alpha (+) female mice with large variations at 4
      months. These extremely high DNA and RNA contents in the TGF alpha (+) group
      declined to the level of the TGF alpha (-) group in the middle of pregnancy and
      at the end of pregnancy, respectively. Thymidine kinase (TK) activity in the
      mammary glands as an index of DNA synthesis was significantly higher in TGF alpha
      (+) mice than in TGF alpha (-) mice at both 2 and 4 months of age and the high TK
      in TGF alpha (+) mice also declined to the level of TGF alpha (-) mice with
      pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7803703
TI  - Chronic toxicity and tumorigenicity study of aluminum potassium sulfate in B6C3F1
      mice.
AB  - The tumorigenic potential of aluminum potassium sulfate [A1K (SO4)2 12H2O, APS],
      a compound which exists widely in the environment, was investigated in B6C3F1
      mice. APS was administered in the diet for 20 months at dose levels of 1.0, 2.5,
      5.0 and 10.0% (w/w). One group receiving the basal diet served as the control.
      Body weight gain in both sexes was decreased in the 10.0% APS treated group, and
      increased in the 1.0 and 2.5% APS treated groups. The survival rates at the end
      of the dosing period were 73.3% (male) and 78.3% (female) in the control group,
      and 86.7-95.0% (male) and 86.7-91.7% (female) in the APS treated groups. The
      survival rate showed a tendency to increase in both sexes in all the APS treated
      groups. In the tumor pathology, the incidence of hepatocellular carcinoma was
      significantly decreased in the males in the 10% APS treated group. The incidence
      of hepatocellular carcinoma was significantly decreased in females in all groups
      including the control group. As regards the nontumorous pathology, the incidence
      of myocardial eosinophilic cytoplasm showed a significant dose-dependent decrease
      in males in the APS treated groups. A comparison between the sexes revealed a
      significant decrease in the incidence of hepatocytic anisonucleosis, myocardial
      eosinophilic cytoplasm and acinar cell vacuolation of the submandibular gland in
      the females; and lymphocyte infiltration in renal cortex and pelvis, and
      vacuolation of cerebellar white matter were noted in the males. The results of
      the present study indicate that long-term administration of APS does not exert
      tumorigenic or any other toxic actions in B6C3F1 mice.

PMID- 7803704
TI  - Defective natural killer activity in gastric cancer patients: possible
      involvement of suppressor factor receptor.
AB  - The mechanism of defective natural killer (NK) activity in gastric cancer
      patients was studied with respect to the soluble immune suppressor factor
      receptor on NK cells. Phycoerythrin (PE)-conjugated anti-CD8 and -CD16 antibodies
      were used for the determination of NK phenotype, and fluorescein isothiocyanate
      (FITC)-conjugated wheat germ agglutinin (WGA) was for the lymphocyte surface
      receptor of soluble immune suppressor factor (SISF). It was found that NK
      activity of peripheral blood lymphocytes (PBLs) isolated from gactric cancer
      patients decreased with tumor progression in spite of an increasing tendency of
      their CD16+ population. The WGA+ population of PBLs inversely increased in
      parallel with cancer progression and a significant negative correlation was found
      between NK activity and the WGA+ population. Two-color flow cytometry showed a
      significant increase of WGA+ cells in the CD8dim and CD16+ population in advanced
      cancer patients. It is suggested that an increase of surface receptors for SISF
      on NK cells may, in part, cause the diminished NK activity in gastric cancer
      patients.

PMID- 7803705
TI  - HSP47 as a possible marker for malignancy of tumors in vivo.
AB  - We have developed a rat monoclonal antibody against mouse HSP47 (designated as
      NK47) and investigated the expression of HSP47 in several mouse ascites and solid
      tumors. The expression of HSP47 was not detected in ascites tumors such as P388
      and Ehrlich ascites tumors while HSP47 was markedly expressed in solid tumors
      such as Colon-26, B16 and B16-BL6 melanomas. HSP70, HSC70 and HSP90 were
      expressed in almost the same level among all the tumors examined. These results
      suggest that the expression of HSP47 decreases as the tumor becomes more
      malignant.

PMID- 7803706
TI  - Rat hepatocellular carcinogenesis and proliferating cell nuclear antigen
      expression induced by 3'-methyl-4-dimethylaminoazobenzene.
AB  - The experimental conditions for the induction of rat hepatocellular carcinoma by
      oral administration of 3'-methyl-4-dimethylaminoazobenzene (DAB) were
      established. Hematoxylin-eosin (HE) staining of the liver sections revealed that
      precancerous lesions, characterized by small proliferation nest, hyperplastic
      nodule, oval cell and adenofibrosis, were observed 2 months after DAB
      administration. The highest incidence of hepatocellular carcinoma, trabecular
      carcinoma and mixed form of hepatocellular and cholangiocarcinoma was observed
      after 3-5 months and remained for an additional 2 months, even if the rats were
      continuously fed with DAB-free fodder. Immunohistochemical study with monoclonal
      antibody against proliferation cell nuclear antigen (PCNA) revealed that the
      relative number of PCNA-positive cells increased with the progress of the
      carcinoma. The present study confirms the previously reported usefulness of the
      PCNA immunostaining method for prognosis and assessment of the malignancy of
      carcinoma.

PMID- 7803707
TI  - Development of a nude mouse model of ras-mediated neoplasia using WR21 cells from
      a transgenic mouse salivary tumor.
AB  - A novel cell line (WR21) was derived from a salivary tumor in a male wap-ras
      transgenic mouse. Salivary tumors in wap-ras transgenic mice are extremely
      aggressive and express high levels of oncogenic ras protein from the activated,
      human Ha-ras transgene. WR21 cells also expressed high levels of oncogenic ras
      protein in vitro and in vivo. They gave rise to aggressive, highly anaplastic
      solid tumors when injected subcutaneously into athymic nude mice and
      approximately 90% of the mice had lung metastases by the fifth week of tumor
      growth. WR21 tumors were inhibited by cyclophosphamide, 5-fluorouracil,
      adriamycin, mitomycin C and actinomycin D, but not methotrexate. Our results
      suggest that the WR21/nude mice model will be useful for testing the efficacy of
      drug therapies against ras-mediated neoplasias.

PMID- 7803708
TI  - Regulation of pyrimidine nucleotide synthesis in rat hematopoiesis.
AB  - In an attempt to define a regulation of pyrimidine nucleotide synthesis in
      hematopoietic cells, we investigated the activities of thymidylate synthetase and
      thymidine kinase, and the cell cycle by flow cytometric DNA analysis and
      bromodeoxyuridine-immunohistochemistry during the recovery phase of hematopoietic
      cells in bone marrow after the hypoplastic period induced by cyclophosphamide
      treatment in rats. The hematopoietic cells first entered into cell cycle via the
      de novo pathway in pyrimidine nucleotide synthesis, and were secondly
      proliferated and differentiated via the salvage pathway. S-phase cells associated
      with a myeloid hematopoiesis increased earlier than those associated with an
      erythroid hematopoiesis in the recovery phase of in rat bone marrow.

PMID- 7803709
TI  - In vivo augmentation of the intratumoral concentration of 5-fluorouracil by
      cepharanthine--a biscoclaurine alkaloid.
AB  - We have investigated the interaction between Cepharanthine (CEP), a multi
      functional alkaloid that has the capacity to stabilize the cell membrane, and 5
      fluorouracil (5-FU) against a human colon cancer cell line (RPMI 4788)
      transplanted into nude mice. Their anti-tumor effects were assessed in a group of
      7 mice intravenously injected with CEP (5 mg/kg/day) and/or 5-FU (15 mg/kg/day)
      during a 3-week treatment. The results were compared with a control and a 5-FU
      group, which received saline solution and 5-FU alone, respectively. The tumors
      were harvested 2 h after 5-FU administration. On an additional 4 groups of 5
      mice, the intratumoral concentration of 5-FU was assessed by a high performance
      liquid chromatographic (HPLC) method 2, 4, 6 and 12 h following CEP (5 mg/kg)
      injection 1 h prior to, simultaneously, and 1 h after injection of 5-FU (30
      mg/kg). The mean (SD) intratumoral concentration of 5-FU was 0.16 (0.05) mu g/g,
      0.32 (0.19) mu g/g, 0.32 (0.16) mu g/g and 0.21 (0.13) mu g/g in the control and
      the three other groups treated with CEP, respectively. This concentration was
      about twice as high in mice simultaneously treated with CEP compared to those
      treated by 5-FU alone. Relatively higher concentrations of 5-FU were noted up to
      4 h following 5-FU injection in mice treated with CEP than in those injected only
      with 5-FU. CEP also enhanced the inhibitory effects of the 5-FU on tumor growth
      rate.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7803710
TI  - Off-treatment course of cisplatin-induced dorsal root ganglia neuronopathy in
      rats.
AB  - As yet little is known about the off-treatment course of cisplatin (CDDP)
      neurotoxicity. In this study we evaluated in the rat how the pathological changes
      in dorsal root ganglia (DRG) neurons and the electrophysiological alterations in
      peripheral nerves induced by chronic CDDP administration evolved after drug
      withdrawal. Twelve female Wistar rats were treated with CDDP and 3 of them were
      sacrificed 1, 5, 10 and 20 weeks after treatment. The results of the experiment
      indicated that: 1) the damage induced by sub-lethal doses of CDDP in the DRG
      neurons is reversible, 2) the first structures to be damaged are the DRG neurons
      (mostly their nucleoli) and 3) both damage and recovery in the follow-up period
      involve first the DRG neurons and subsequently the peripheral nerves.

PMID- 7803711
TI  - Glycyrrhizin and 18 beta-glycyrrhetinic acid: a comparative study of the
      pharmacological effects induced in the rat after prolonged oral treatment.
AB  - Recent clinical and toxicological studies have investigated the mineralcorticoid
      like and hypertensive effects of liquorice, and we therefore set out to identify
      the active component responsible for these effects. We conducted a 30-day
      comparative analysis of glycyrrhizin and 18 beta-glycyrrhetinic acid and found
      that the latter causes significant variations both in systolic blood pressure and
      in the excretion in the urine of Ca++. The effects were fully reversible on
      suspension of treatment.

PMID- 7803712
TI  - Metastasis of human colon tumor cells in vivo: correlation with the
      overexpression of plasminogen activators and 72 kDa gelatinase.
AB  - Metastatic spread of tumor cells depends upon intravasation of malignant cells
      from the primary site and extravasation into the distant organs following
      remodeling of the basement membrane. We have investigated the metastatic
      potential of five tumorigenic human colon carcinoma cell lines, LS 174T, SW 620,
      WiDr, SW 480 and Caco-2 using intrasplenic injection in nude mice. LS 174T is
      most aggressive causing liver metastasis in all animals within 6 weeks. SW 620
      and WiDr produced liver metastasis in 70% and 30% of the animals but after a
      period of 12 weeks whereas SW 480 and Caco-2 were not metastatic. LS 174T
      exhibited high cell-associated urokinase-type plasminogen activator (u-PA) and
      high secreted u-PA and tissue plasminogen activator (t-PA) levels. WiDr, SW 480
      and Caco-2 had essentially similar low levels of cell associated u-PA but WiDr
      had higher secreted u-PA levels as comprated to the SW 480 and Caco-2 cells. The
      level of secreted MMP-2 (72 kDa gelatinase) was highest in the most metastatic
      cell line, LS 174T, and lower in other less metastatic ones. These data show that
      metastatic behavior of human colon tumor cells correlates with the enhanced
      secretion of plasminogen activators and MMP-2 by these cells.

PMID- 7803713
TI  - Comparison of single- and dual-energy quantitative computed tomography for
      therapy control under antiosteoporotic treatment.
AB  - Lumbar spine bone mineral density was determined in 50 female patients (mean age:
      55.4 +/- 12.3 years), who were treated because of osteoporosis or osteopenia.
      Bone mineral density was assessed using single-energy QCT with 80 and 120 kV tube
      voltage and with dual-energy QCT. Compared to single-energy QCT, dual-energy QCT
      showed much higher variability of the bone density values obtained. Therefore we
      conclude that single energy QCT is a method that allows precise and reproducible
      determination of spinal bone mineral content under clinical conditions which
      cannot be further improved by the use of dual-energy QCT.

PMID- 7803714
TI  - Characterization and tumorigenicity of spheroids composed of pigmented or non
      pigmented B16 melanoma cells.
AB  - A parental line of mouse B16 melanoma cells (B16) and two derived cloned lines,
      either pigmented (B16P) or non pigmented (B16NP), were cultured in vitro as
      spheroids. After 48 hrs, the pigmented cells (B16, B16P) formed smaller and
      looser aggregates, with higher rates of cell proliferation and lower amounts of
      extracellular matrix as compared to B16NP spheroids. The three lines were more
      tumorigenic when inoculated subcutaneously as spheroids than as isolated cells.
      Furthermore, B16P or B16 spheroids developed richly vascularized subcutaneous
      tumors and metastases more rapidly than B16NP aggregates. After intravenous
      injection of spheroids, the measurement with an image analyzer of the area of
      sections in lung colonies indicated that B16P colonies were larger and more
      numerous than those induced by B16NP cells.

PMID- 7803715
TI  - Persistence of polyomavirus in adult SCID C.B-17 mice.
AB  - C.B-17 mice with the Severe Combined Immune Deficiency (SCID) mutation were
      infected with the naturally occurring murine polyomavirus. Using the Polymerase
      Chain Reaction (PCR) technique, persistence of polyomavirus was followed in
      different tissues of the mice between 24 hours and 2 months post infection
      (p.i.). Viral DNA appeared by 3-5 days and was detected in all studied organs by
      3 weeks p.i. From 4 weeks to 2 months p.i. viral DNA was present at high levels
      in all studied organs in all of the animals. As controls normal C.B-17 and A/Sn
      mice were used. Viral DNA appeared by 2-4 days. The infection reached a peak
      around 1 week p.i. This was followed by a clearing stage and viral DNA was no
      longer detectable by 4-5 weeks p.i. Most organs studied with PCR were also
      examined histologically, but no lesions were observed. Consequently persistence
      and organ distribution of polyomavirus in adult SCID mice differs greatly from
      that in normal adult mice.

PMID- 7803716
TI  - Immunological localization of glycoprotein 330, low density lipoprotein receptor
      related protein and 39 kDa receptor associated protein in embryonic mouse
      tissues.
AB  - In this study we have immunologically examined the expression of the structurally
      and functionally related receptors, LRP and gp330, and their associated 39 kDa
      protein (RAP) in tissues of the embryonic mouse. One aim was to determine whether
      these proteins were coordinantly expressed. The data reveals that gp330 is
      expressed on the apical surfaces of many specialized absorptive epithelia most
      prominently, choroid plexus, ependyma, metanephric tubules, ear, thyroid,
      pericardium, and intestine. LRP was detected in all epithelia expressing gp330
      with the exception of the epicardium and metanephric tubule epithelium. However,
      the subcellular pattern of LRP deposition in polarized epithelium was distinct
      from the apical pattern of gp330, perhaps indicating that LRP was either
      sequestered intracellularly or distributed basolaterally. The pattern of LRP
      expression in tissues of the mouse embryo was however much wider than that of
      gp330. Prominent expression of LRP was observed in skin, myocardium, mesenchyme,
      liver, pancreas, and marginal regions of the brain. In the developing liver, LRP
      was not detected in day 10.5 but was detected in megacaryocyte-like cells of 12.5
      day and in hepatocytes of 14.5 day embryonic liver. RAP was observed to be
      coexpressed with either or both of the receptors but its subcellular pattern of
      distribution coincided with that of LRP. The coexpression of gp330 and LRP in
      epithelial cells and the observation that gp330 staining was always localized
      apically while LRP was distributed basolaterally or sequestered intracellularly
      suggests that these receptors have distinct functions in polarized epithelial
      cells.

PMID- 7803717
TI  - Dexamethasone-induced histopathology of neonatal rat myocardium.
AB  - Dexamethasone-induced relative cardiomegaly in neonatal rats mimics hypertrophic
      cardiomyopathy seen in premature infants receiving dexamethasone for
      bronchopulmonary dysplasia. Dexamethasone reduced cellular density by
      approximately 20%. However, dose related increases in mean fiber diameter were
      seen and mitotic index was doubled at 12.5 micrograms dexamethasone/injection. In
      addition, dexamethasone induced collagen accumulation throughout the myocardium
      in an apparently dose dependent manner. These data suggest that dexamethasone
      promotes (i) myocardial hypertrophy and possibly hyperplasia and (ii) fibrosis
      and possibly fibroplasia. Further studies are required to determine relationships
      between disseminated collagen deposition and other suggested metabolic changes
      and the observed compensatory myocardial hypertrophy and hyperplasia.

PMID- 7803718
TI  - Comparison of DNA flow cytometric analysis of body cavity fluids with
      conventional cytology.
AB  - The potential utility of flow cytometric (FCM) analysis in routine diagnostic
      cytology for effusions was assessed with 104 samples from body cavity fluids.
      Conventional cytology showed no positivity (0/33) for effusions from patients
      with non-malignant diseases, and 45% positivity (38/71) for effusions from
      patients with malignant diseases. Conversely, FCM showed no positivity
      (aneuploid) (0/33) for effusions from patients with non-malignant diseases, and
      18% positivity (13/71) with malignant diseases. In 13 cases examined, 8 cases
      (62%) showed an identical DNA ploidy pattern between effusion site and primary
      site. FCM showed positivity in four cytologically negative samples (3 malignant
      lymphomas and 1 clear cell carcinoma). In cases with malignant lymphoma,
      conventional cytology showed 40% positivity (4/10) and FCM 60% (6/10) positivity.
      These results indicate that DNA analysis of cells in malignant effusions does not
      have a diagnostic value as a routine test, but it may have in cases of malignant
      lymphoma.

PMID- 7803719
TI  - Ultrastructural study on the development of the rat [correction of mouse]
      spermatocyte nuclear matrix during epididymal maturation.
AB  - The rat sperm nucleus, after sequential extraction with detergents, nuclease and
      ammonium sulfate, consists of a skeletal structure that resembles the original
      nuclear shape. This chromatin-depleted skeleton is formed by thick and thin
      fibers as well as globular structures of different sizes. These fibers form
      anastomosis. The sperm nuclei obtained from testis and caput epididymis exhibits
      a loose fibrous network with thin fibers at the center. The entire nucleus of the
      sperm in the caudal epididymis is formed by a dense network of thick and thin
      fibers. These highly branched matrix fibers had diameters of 35 and 12 nm. It is
      concluded that the increase in density of the matrix fibers is related to the
      condensation of the chromatin in the maturation of the spermatozoa.

PMID- 7803720
TI  - Breast cancer in first degree relatives of 180 female breast cancer patients.
AB  - The risk of breast cancer and of all malignancies was assessed in first degree
      relatives of 180 women with breast cancer using a historical cohort study
      approach. The standardized incidence ratio (SIR) was significantly (p < 0.05)
      increased for breast cancer in mothers: 1.97 (95% Confidence Interval (CI): 1.27
      to 2.91) and in all female first degree relatives: 1.55 (95% CI: 1.08 to 2.15).
      For breast cancer in sisters it was 1.12 (95% CI: 0.56 to 2.01). For all
      malignancies the SIR for mothers was 1.12 (95% CI: 0.85 to 1.44), for sisters
      1.09 (95% CI: 0.77 to 1.49) and for all female first degree relatives 1.08 (95%
      CI: 0.89 to 1.32). This study confirms previous investigations showing that
      breast cancer occurs more frequently in female first degree relatives of women
      with breast cancer than in the general population.

PMID- 7803721
TI  - Inhibitory effects of purified eicosapentaenoic acid and docosahexaenoic acid on
      growth and metastasis of murine transplantable mammary tumor.
AB  - We studied the effects of purified linoleic acid, eicosapentaenoic acid(EPA) and
      docosahexaenoic acid (DHA) on mammary tumor MM48 the transplanted into C3H/He
      mice. The growth of the primary tumor was significantly inhibited in EPA- and DHA
      treated groups as compared with control and/or linoleic acid-treated groups (p <
      0.05). The number of metastatic tumors in the lungs tended to be inhibited in the
      EPA- and DHA-treated groups and promoted in the linoleic acid-treated group, as
      compared with the control group, but not to a statistically significant extent.
      The EPA-treated group survived significantly longer than the control group (p =
      0.002), while the DHA-treated group survived longer than the control group
      although the difference was not significant (p = 0.070). However, there was no
      significant difference between EPA- and DHA-treated groups on primary tumor
      growth, number of lung metastases or survival time of animals.

PMID- 7803722
TI  - Synergistic inhibition of AZT-resistant HIV by AZT combined with
      poly(I):poly(C12U), without synergistic toxicity to bone marrow progenitor cell
      elements.
AB  - Mutation of human immunodeficiency virus (HIV) to drug resistance is an obstacle
      to HIV containment, and may account for the transitory nature of the improvement
      in CD4 cell counts of patients receiving azidothymidine (AZT). The emergence of
      AZT-resistant (AZTR) virus might be suppressed if a second therapeutic could be
      added; however, such a regimen would have to confer not only additional control
      over HIV replication but also no additional toxicity, especially to bone marrow
      progenitor cells. In the present study, HIV was isolated from patients receiving
      AZT alone and was studied for sensitivity to the mismatched double-stranded RNA,
      poly(I):poly(C12U) (ampligen). In addition, the combination of poly(I):poly(C12U)
      plus AZT was studied in vitro for toxicity to bone marrow CFU-GM and in patients
      receiving combined therapy for bone marrow toxicity. HIV isolated from patients
      receiving AZT alone showed higher resistance to AZT than wildtype virus, but
      remained sensitive to poly(I):poly(C12U). Poly(I):poly(C12U) and AZT were
      synergistic in inhibiting all isolates of HIV tested, regardless of their AZTR
      phenotype. Furthermore, the combination of poly(I):poly(C12U) and AZT showed no
      toxicity in vitro to bone marrow CFU-GM compared to AZT alone. In 11 HIV infected
      individuals receiving the combinational regimen, bone marrow function gradually
      improved. These results indicate that poly(I):poly(C12U) was active against AZTR
      HIV, synergistic with AZT and did not convey added toxicity.

PMID- 7803723
TI  - Enhancement of transplantable neoplastic tissue growth in rats by ligated
      vasectomy and long-term exercise.
AB  - The long-term effects of vasectomy and exercise upon incidence and frequency of
      neoplastic lesions in preselected categories, number of neoplasms by morphologic
      type, anatomic site and weight, selected body and organ weights, and survival
      experience of rats receiving a transplantable pancreatic carcinoma were
      determined. Vasectomy-exercise subjects had a significantly greater incidence of
      neoplasms at multiple anatomic sites as compared to sedentary subjects, but not
      with other exercised ones. Vasectomy-sedentary subjects had a higher incidence of
      multiple neoplastic lesions of the same anatomic site than sedentary controls.
      Ligated vasectomies may accelerate transplantable neoplastic tissue growth.
      Vasectomy-exercise subjects had a greater total number of discrete, fused, both
      discrete and fused neoplasms, and different anatomic sites of fused neoplasms
      compared to sedentary controls. Ligated vasectomy groups had significantly
      heavier body weights at necropsy than shamvasectomized control groups. Sham
      vasectomy-exercise subjects had significantly heavier relative liver weights than
      shamvasectomy-sedentary controls. There was not a significant difference between
      groups in survival experience. Conditions associated with the ligated-vasectomy
      state and the physiologic consequences of moderate exercise may accelerate
      transplantable neoplastic tissue growth in Lewis rats.

PMID- 7803725
TI  - Proceedings of the 1st International Conference on the Epidemiology of Early
      Prostate Cancer. Detroit, Michigan, November 17, 1993.

PMID- 7803724
TI  - Is Linus Pauling, a vitamin C advocate, just making much ado about nothing?
      (Review).
AB  - Clinical use of vitamin C has been the subject of much debate in both the USA and
      Japan. We examine a number of topics to clarify the reasons for the confrontation
      of opinion between the pros and the cons as to the medical usefulness of this
      vitamin. We refer to our own experiences on the use of vitamin C infusion
      treatment for the control of either diabetes mellitus or autoimmune disease and
      allergy to show the importance of pharmacological considerations in the
      assessment of the effect of vitamin C. We also refer to a number of scientific
      debates to prove that a shift of paradigm is indispensable for getting a full
      comprehension of the benefits of vitamin C including the control of both diabetes
      mellitus and autoimmune disease/allergy complex.

PMID- 7803726
TI  - Epidemiology of early prostate cancer (introduction).
AB  - The number of prostate cases reported is increasing markedly in the United States
      and worldwide. The cause for the increase as well as the reason for the marked
      geographic and racial differences in the epidemiology of prostate cancer, is
      poorly understood. Nevertheless, such information is essential for understanding
      the biology of the disease, and for the rational implementation of detection
      strategies, disease prevention, and appropriate treatment. These important
      epidemiological concerns were recently discussed at an International Symposium on
      the Epidemiology of Early Prostate Cancer.

PMID- 7803727
TI  - The epidemiology of prostate cancer: clues for chemoprevention.
AB  - Prostate cancer exists as two different clinical entities; a "latent" or
      "histologic" form and a clinically evident form. While the prevalence of
      histologic prostate cancer is similar around the world, the prevalence of
      clinical cancer varies dramatically from country to country. This suggests that
      promotional events which contribute in the transformation of histologic cancer to
      clinically important cancer vary from country to country and population to
      population. The ultimate goal of epidemiologic studies is to identify risk
      factors, i.e., promotional agents, for prostate cancer and to use this knowledge
      for disease prevention strategies.

PMID- 7803728
TI  - Costs and benefits of prostate cancer screening. Investigators of the American
      Cancer Society--National Prostate Cancer Detection Project.
AB  - Optimal combinations of digital rectal examination (DRE), transrectal ultrasound
      (TRUS) and prostate specific antigen (PSA) may better detect patients at high
      risks, as well as those in whom continued screening may not be cost effective.
      Our recent cost analysis of prostate cancer early detection used current data
      from three consecutive years of the American Cancer Society's National Prostate
      Cancer Detection Project. Marginal cost analysis showed marked increased costs
      for the DRE by year three due to significantly reduced sensitivity for incident
      cancers. The benefit-cost equation acknowledges that many parameters of both cost
      and probability are not definitive at this time, yet illustrated major points for
      discussion. The cost parameters most sensitive to incremental change in
      decreasing order are: the specificity of the screening test > benefits obtained
      from early therapy > prevalence of the disease. Benefit-cost calculations
      demonstrated that DRE, when performed by highly skilled examiners, had the lowest
      cost. However, DRE became one of the most costly detection scenarios when a minor
      decrease in DRE performance was assumed for more general examiners. If slightly
      more specific PSA usage (or assay) is developed, the higher prevalence of
      clinically detectable prostate cancer could make screening less costly than
      breast cancer screening. If we assume minimized future expenditures for terminal
      cancer care via reductions in therapy choices or coverage, no economic benefit
      for screening exists. If we also assume that potential costs to society are not
      roughly approximated by any benefits, we may engender inappropriate attempts at
      cost reduction by effectively discouraging screening in the highest risk
      groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7803729
TI  - The increasing incidence of prostate cancer in Hungary.
AB  - Prostate cancer is becoming an increasing health concern world wide, and its
      significance is also increasing in Hungary, where mortality rates are very
      similar to those in the United States of America. Mortality from prostate cancer
      is increasing disproportionately to the aging of Hungarian men or overall
      population growth, and the explanation for this alarming trend is as yet
      unexplained. Nevertheless, the data suggest that prostate cancer will continue to
      assume increasing importance as a medical problem and the need for fundamental
      epidemiologic investigations is clear.

PMID- 7803730
TI  - Prostate cancer in Canada.
AB  - The early detection and treatment of men with prostate cancer is a complex and
      urgent challenge faced by most of the worlds' nations. In Canada, its
      significance is increasing in parallel to that of the United States. With
      increasing incidence, the implications for intervention in terms of quality of
      life and the utilization of health care resources must be continually reassessed.
      In this article, the epidemiology and the screening of prostate cancer as it
      pertains to Canadian men and the Canadian Health Care system are discussed.

PMID- 7803731
TI  - High grade prostatic intraepithelial neoplasia (HGPIN) and prostatic
      adenocarcinoma between the ages of 20-69: an autopsy study of 249 cases.
AB  - The relationship of prostatic intraepithelial neoplasia (PIN) and invasive
      carcinoma of the prostate is not fully understood. It is generally accepted that
      HGPIN is a probable preinvasive malignant change or at least a marker lesion for
      carcinoma. The prevalence of HGPIN in younger men is not known. Two hundred and
      forty nine entirely processed prostates from men aged 20-69 were thoroughly
      evaluated for the presence of PIN and carcinoma. The histologic diagnosis of all
      positive cases was confirmed by two pathologists. Our results are summarized as
      follows: Seventy seven percent of the prostates with HGPIN harbored
      adenocarcinoma, whereas the frequency of cancer in prostates without HGPIN was
      24%. HGPIN was encountered in 0, 5, 10, 41 and 63% of men in the 3rd, 4th, 5th
      and 7th decades, respectively. The corresponding figures for invasive carcinoma
      were 2, 29, 32, 55, and 64% respectively.

PMID- 7803732
TI  - The frequency of latent prostatic carcinoma in young males: the Japanese
      experience.
AB  - Prostates obtained at autopsy from five different ethnic groups were serially
      step-sectioned and examined microscopically using identical techniques and
      diagnostic criteria. The groups consisted of African-American and white males
      from the United States of America, Japanese immigrants in Hawaii, and Japanese
      men in Japan. The prostates were collected between 1965 and 1979. The fifth group
      consisted of newly collected prostates from indigenous Japanese between 1982 and
      1986. The frequency of latent prostatic carcinoma from men under 50 years of age
      was compared to each other and with those from men over 50 years of age. Latent
      carcinoma was not found in men between 30 and 39 years old in any groups except
      indigenous Japanese men (6%) who died from 1982 to 1986. The frequency of latent
      carcinoma in the patients in fifth decade varied from 0 to 20%. Latent tumor was
      not found in the African-Americans in the fifth decade. There was an age
      dependent increase in prostate cancer in all groups. The Japanese prostates from
      1982 to 1986 had a higher rate of latent cancer than the ones from 1965 to 1979
      in each decade. International comparison of the latent prostatic carcinoma from
      the patients under 50 years of age showed similar tendency as those from over 50
      years old, Japanese men had a marked increase in the frequency of latent prostate
      cancer from 1965-1979 to 1982-1986. These data suggest that the prevalence of
      prostate cancer may be increasing worldwide.

PMID- 7803733
TI  - Early detection issues of prostate cancer in African American men.
AB  - There were 35,000 deaths from prostate cancer estimated in 1993. The mortality
      rate among African American men from prostate cancer is 2-3 times higher than
      among Caucasian Men between the ages of 50-70. There may be many reason for this
      disproportionate mortality such as a genetic basis, diet or a difference in
      doubling time between the ethnic groups. Differences in access to care has also
      been suggested as a cause for this difference. But what has been clearly
      demonstrated is that African Americans are diagnosed with prostate cancer at a
      more advanced stage. Thus, health seeking barriers that delay the diagnosis of
      prostate cancer until cure or long-term quality survival is no longer possible,
      may be a primary reason for this disproportionate mortality. Since a higher
      percentage of African Americans present with advanced and remote prostate cancer,
      it seems reasonable to focus our attention on programs directed towards early
      detection of prostate cancer in this high risk population. However there are
      several controversies associated with early detection such as its benefit, over
      treatment, and cost. Perhaps the investigation and resolution of these issues
      should begin in a high risk population.

PMID- 7803734
TI  - Can our patients afford the cost of cost containment?

PMID- 7803735
TI  - Hemodynamic and pharmacodynamic comparison of doxacurium and high-dose vecuronium
      during coronary artery bypass surgery: a cost-benefit study.
AB  - Doxacurium (DOX), a new nondepolarizing neuromuscular blocking drug (NMBD), was
      compared in a randomized, double-blind fashion to high-dose vecuronium (VEC) in
      60 coronary artery bypass grafting (CABG) patients. A third group of 15 patients
      older than 70 years of age (DOX-70) was added to compare the effects of DOX to
      VEC in the older population. Endpoints of the study were hemodynamic stability,
      ease of ventilation and intubation, anesthesiologist's satisfaction, drug
      interventions to correct hemodynamic instability, and total cost of the drug.
      Anesthesia was induced with fentanyl (30 micrograms/kg) along with the NMBD (DOX
      80 micrograms/kg, VEC 400 micrograms/kg) over a 2-minute period. Following
      induction, heart rate (HR) and mean arterial pressure (MAP) were decreased (P <
      0.01) in all groups. Tracheal intubation caused the HR to return to baseline in
      the DOX-70 group. There was no difference in central venous pressure, pulmonary
      artery occlusive pressure, cardiac index, systemic vascular resistance, and drug
      intervention for DOX and VEC. None of the patients had evidence of myocardial
      ischemia. There was a statistically significant but clinically irrelevant
      decrease in central venous pressure and systemic vascular resistance in the DOX
      70 group. The durations of the induction and maintenance doses of DOX were
      similar in the younger and older patients. Although the intubating dose of VEC
      had a faster onset of action, this had no effect on the ease of ventilation,
      conditions for tracheal intubation, and overall anesthesiologist satisfaction.
      The total cost for each NMBD was not different.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7803736
TI  - Oxygenation and ventilation characteristics of thoracic surgical patients the
      night before surgery.
AB  - Studies of the respiratory effects of perioperative analgesic and anesthetic
      agents are complicated by evidence that healthy subjects and those with COPD may
      have abnormalities of oxygenation and ventilation during sleep. This report thus
      characterizes respiration during sleep preoperatively in a population frequently
      examined in postoperative analgesia studies. Sixty-two thoracic surgical patients
      were monitored by continuous respiratory inductive plethysmography, 49 of whom
      also had continuous pulse oximetry and bi-hourly blood gas measurements. The mean
      respiratory rate (RR) at each hour during sleep was similar to the awake RR (P >
      0.06). The minimum RR during sleep was 7.6 +/- 2.1 (2.6-9.8; median 7.9). At
      least 1 apnea (tidal volume < 100 mL for > or = 15 sec) occurred in 77% of
      subjects, and 32% had > or = 1 slow respiratory rate (SRR; 5-min RR < 10
      beats/min) episode. The mean SpO2 for hours 2 to 4 was significantly less than
      while awake (P < 0.0015), but the differences were < or = 1.1%. The minimum SpO2
      was 88 +/- 7% (62-97; 89) and 40% of subjects had > or = 1 desaturation (DESAT90;
      SpO2 < 90% for > or = 15 sec) episode. The pH at hours 2 and 4 was significantly
      (P < 0.0009) less than while awake, but the differences were only 0.02. Other bi
      hourly pH, PaCO2, and PaO2 values were similar to the awake values (P > 0.02).
      Interpatient variability was high, especially for episodic
      abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7803737
TI  - Respiratory function after cardiopulmonary bypass: a comparison of bubble and
      membrane oxygenators.
AB  - A consecutive sample of 500 adults undergoing cardiac surgery was randomly
      allocated to extracorporeal circulation with either a Bard bubble oxygenator
      H1700 or a Bard membrane oxygenator HF5700 (Bard Ltd, Crawley, UK). Alveolar
      arterial oxygen tension gradient (AaDO2) was calculated prebypass, then 20, 90,
      180, and 420 minutes postbypass. Preoperative, initial postoperative, and first
      day postoperative chest x-rays were assigned an extravascular lung water (EVLW)
      score and an atelectasis score. There was a comparable increase in AaDO2 after
      bypass in each group. The increase in EVLW score was significantly greater in the
      bubble group (mean 2.91, 95% CI 2.28-3.54) than the membrane group (mean 2.06,
      95% CI 1.43-2.69) for the initial postoperative x-rays (P < 0.01) and also for
      the x-rays on the first postoperative day (P < 0.01). The increase in atelectasis
      score was significantly greater in the bubble group (mean 1.06, 95% CI 0.94-1.18)
      than the membrane group (mean 0.86, 95% CI 0.74-0.98) for the initial
      postoperative x-rays (P < 0.01) but not for the x-rays on the first postoperative
      day. There was no difference in duration of ventilation, intensive care, hospital
      stay, or hospital mortality between bubble and membrane groups. Although there
      was a statistically significant difference in x-ray scores between oxygenator
      groups, neither intrapulmonary shunting nor clinical outcome was influenced by
      the type of oxygenator used during bypass.

PMID- 7803738
TI  - Early extubation after cardiac surgery using combined intrathecal sufentanil and
      morphine.
AB  - The records of 10 patients who had well-preserved respiratory and ventricular
      function and had received 50 micrograms of sufentanil and 0.5 mg of morphine
      intrathecally before induction of anesthesia for cardiopulmonary bypass surgery
      were reviewed. Anesthesia was maintained with isoflurane and no patient received
      intravenous narcotics intraoperatively. Postoperative analgesic requirements were
      low, with 7 of 10 patients requiring no supplemental analgesic during the first
      12 hours. Early extubation (within 8 hours of arrival in the intensive care unit)
      was possible in 8 patients; two patients remained intubated for reasons unrelated
      to the anesthetic technique. No patient required naloxone, reintubation, or
      treatment for respiratory depression. Combined intrathecal sufentanil and
      morphine provided conditions that allowed successful early extubation in 8 of 10
      of these selected cardiac surgery patients.

PMID- 7803739
TI  - Use of the activated coagulation time and heparin dose-response curve for the
      determination of protamine dosage in vascular surgery.
AB  - The activated coagulation time (ACT) can be used to construct a two-point heparin
      dose-response curve (HDRC) from the ACT values at baseline and 5 minutes after
      heparin administration. The ACT value at any subsequent time interval can then be
      used to estimate the residual heparin activity from the HDRC. The protamine dose
      is calculated to be the amount of residual heparin multiplied by a correction
      factor (1.3 was suggested for cardiac surgery). In vascular surgery, heparin and
      protamine dosing remain empirical, ACT monitoring is not standard, and use of the
      HDRC has not been previously investigated. Forty-five patients were prospectively
      randomized to one of three groups. ACT was measured before heparinization (1
      mg/kg, 1 mg = 100 U), 5 minutes later, and then every 30 minutes until just prior
      to and after protamine administration. Group I received 1 mg/kg of protamine. In
      Groups II and III the residual heparin activity was interpolated from the HDRC
      and multiplied by 1.3 or 1.0, respectively, to derive the protamine dosage.
      Randomization created balanced groups with respect to demographic data. The
      individual peak effect of heparin ranged from 177% to 401% of control. The ACT
      returned to control after protamine in all groups. The protamine dose was
      significantly less when the HDRC was used (P < 0.05). Group III received the
      least protamine (0.64 +/- 0.07 mg/kg, P < 0.05). No adverse protamine reactions
      or postoperative bleeding occurred. It is concluded that ACT monitoring and use
      of the HDRC provides a safe and easy method to individualize protamine dosage in
      vascular surgery.

PMID- 7803740
TI  - Perioperative management and outcome of patients having cardiac surgery combined
      with abdominal aortic aneurysm resection.
AB  - Patients with abdominal aortic aneurysms (AAA) have a high incidence of
      associated cardiac disease. If a patient presents with both severe coronary
      artery disease and a large AAA, a staged procedure of cardiac surgery (CS)
      followed by AAA resection may present too great a risk of aneurysm rupture and
      death. A combined procedure may be recommended in this circumstance; however, the
      literature contains only individual successful case reports of such a procedure.
      A series of 10 patients who underwent CS and AAA repair to define the risks and
      outcome of this complex patient population is presented. Methods used included a
      retrospective analysis of hospital chart data from patients undergoing combined
      CS and AAA resection from 1980 to the present at this institution. The data
      analyzed included age, sex, chief complaint, past medical history, indications
      for surgery, abdominal aneurysm size, coronary anatomy, valvular pathology,
      preoperative left ventricular function, anesthetic agent and dose, order of
      surgery, prebypass complications, intraoperative complications, cardiopulmonary
      bypass time, aortic cross-clamp time, abdominal aortic cross-clamp time, blood
      product use, and postoperative complications. Seven of the 10 patients had a
      successful outcome (S group), whereas 3 of the 10 patients died postoperatively
      (D group). The staged procedure of first performing CS and then the AAA resection
      has a combined operative mortality of 4%. When the nature of both lesions is
      severe and a combined procedure is necessary, there is an associated in-hospital
      mortality of approximately 30% at this institution. The S group patients had an
      unremarkable postoperative course with a relatively short hospital stay when
      compared to the staged procedure.

PMID- 7803741
TI  - Effects of cardiopulmonary bypass on lymphocytes and their subset counts with or
      without use of autotransfusion devices.
AB  - Lymphocytes and their subset counts were determined in 30 cardiac surgery
      patients during cardiopulmonary bypass (CPB) with or without use of an
      autotransfusion device. In the autotransfusion group, centrifuged and washed
      autologous red blood cells (median 400 mL [range 200-770 mL]) and in the control
      group corresponding amounts of homologous packed red blood cells (median 500 mL
      [range 250-750 mL]) were transfused after declamping the aorta. The percentages
      of T lymphocytes (CD3) and T cytotoxic cells (CD8) increased in both groups (CD3
      up to 5%, P < 0.05 and CD8 up to 35%, P < 0.01), but the percentage of T helper
      cells (CD4) did not change. The ratio of CD4/CD8 cells decreased (up to 34%, P <
      0.01). The percentage of naive resting T cells (CD45RA) increased slightly (up to
      8%, P < 0.05) whereas the percentages of memory T cells (CD45RO), T cells with IL
      2 receptor (CD25), and natural killer cells (CD16) remained unaltered. The
      percentage of HLA-DR positive lymphocytes increased during CPB (up to 18%, P <
      0.05), but it was decreased thereafter (up to 16%, P < 0.05). The percentage of
      monocytes (CD14) decreased first during CPB in both groups (up to 32%, P < 0.01),
      but it was higher in the autotransfusion device group (decreased 29% from initial
      value) than in the control group (decreased 65% from initial value) at the end of
      CPB (P < 0.05). This study shows that extracorporeal circulation has an effect on
      lymphocytes and their subset counts. The changes were slightly immunosuppressive.
      By contrast, use of autotransfusion devices had only minor effects.

PMID- 7803742
TI  - Effects of atrial pacing on right ventricular contractility after coronary artery
      surgery.
AB  - Increasing heart rate enhances the strength of contraction of cardiac fibers.
      This has been demonstrated in vitro and recently for the left ventricle. To study
      this phenomenon on the right ventricle, the effects of increasing heart rate by
      atrial pacing on right ventricular (RV) contractility were observed after
      coronary artery surgery in 20 patients. Right ventricular ejection fraction (EF)
      and stroke volume (SV) were measured by use of a rapid-response thermistor
      pulmonary artery catheter. Right ventricular volumes were calculated from EF and
      SV. Right ventricular contractility was assessed by the slope of the end-systolic
      pressure-volume relationship (ESPVR) before and after increasing RV preload by
      means of military antishock trousers (MAST) inflation. The dP/dtmax/end-diastolic
      volume index (EDVI) ratio, which is independent of ventricular preload, was also
      used as an inotropic index. Results are expressed as mean +/- SEM. Right
      ventricular preload, as reflected by RVEDVI, was increased by MAST inflation (99
      +/- 6 mL/m2 v 106 +/- 7 mL/m2, P < 0.01), but returned to control values when
      inflation of MAST was combined with pacing (100 +/- 6 mL/m2). The slope of the RV
      ESPVR significantly increased when heart rate was increased (0.22 +/- 0.03
      mmHg/mL/m2 before pacing v 0.77 +/- 0.07 mmHg/mL/m2 during pacing, P < 0.05). The
      dP/dtmax/EDVI ratio was also increased by pacing (2.32 +/- 0.4 mmHg/min/mL/m2
      before pacing v 3.15 +/- 0.5 mmHg/min/mL/m2 during pacing, P < 0.01). Moreover,
      cardiac index was increased by pacing alone (2.45 +/- 0.2 L/min/m2 v 2.78 +/- 0.2
      L/min/m2, P < 0.01), and significantly more when MAST were inflated (2.94 +/- 0.2
      mL/m2, P < 0.05 v pacing alone). It is concluded that increasing heart rate by
      atrial pacing increases RV inotropic status after coronary artery surgery.

PMID- 7803743
TI  - Influence of intravenous calcium gluconate on saphenous vein graft flow in closed
      chest patients.
AB  - The effects of calcium gluconate on hemodynamics and saphenous vein graft flow in
      a group of patients undergoing elective coronary artery bypass grafting who
      developed ionized hypocalcemia at the end of the surgical procedure were
      examined. The patients received a central venous bolus of 15 mg/kg of calcium
      gluconate. Heart rate (HR), arterial pressure (AP), central venous pressure
      (CVP), pulmonary artery pressure (PAP), pulmonary capillary wedge pressure
      (PCWP), and cardiac output were measured immediately before and 30, 60, 120, 180,
      and 240 seconds after injection of calcium gluconate. Systemic and pulmonary
      vascular resistance (SVR and PVR, respectively), cardiac index (CI), stroke
      volume index (SVI), and right and left ventricular stroke work index (RVSWI and
      LVSWI, respectively), were calculated. Venous bypass flow velocity (Vbypass-flow)
      was assessed using a Doppler probe that was attached to the left anterior
      descending artery (LAD) bypass intraoperatively. Calcium gluconate significantly
      increased MAP, SVR, and LVSWI from 67 +/- 3 mmHg (mean +/- SEM), 1,128 +/- 128
      dyne.s.cm-5 and 25 +/- 3 g.m.beat/m to a maximum of 81 +/- 5 mmHg (P < 0.01),
      1,401 +/- 196 dyne.s.cm-5 (P < 0.05), and 32 +/- 4 g.m/beat/m (P < 0.01),
      respectively. HR, CVP, PAP, PCWP, PVR, CI, SVI, and Vbypass-flow remained
      unaltered. It is concluded that calcium gluconate administered to moderately
      hypocalcemic patients increases arterial pressure mainly by peripheral
      vasoconstriction. Because the increase of arterial pressure, and, thereby,
      coronary perfusion pressure is not associated with an increase of LAD bypass
      flow, vasoconstriction in the coronary vascular bed distal to the venous graft
      cannot be ruled out, and deterioration of the myocardial oxygen supply/demand
      ratio is strongly suggested.

PMID- 7803744
TI  - Hemodynamic responses to dobutamine during acute normovolemic hemodilution.
AB  - The effects of dobutamine (DOB) on myocardial performance, systemic hemodynamics,
      and oxygen delivery during acute normovolemic hemodilution in anesthetized rats
      were studied. Forty-two Sprague Dawley rats (body weight 375 to 425 g) were
      divided into six equal groups. Hemodynamic and cardiac indices were measured or
      calculated at baseline, 30 minutes after the initiation of hemodilution (HD), and
      15 minutes after DOB or saline infusion. Myocardial performance in response to
      acute pressure or volume loads was studied in all groups of animals. HD to a
      hematocrit (Hct) value of 20% resulted in no change in heart rate (HR), increased
      CI, SVI, and LV dP/dt, and decreased MAP, SVRI, and oxygen delivery index (O2DI).
      HD increased peak SV and CI after preload stress while the left ventricular
      developed pressure (LVDP) was unchanged. Infusion of DOB as 7.5 or 15
      micrograms/kg/min increased HR, CI, and LV dP/dt as well as LVDP. At the same
      time, DOB decreased MAP and SVR, whereas the SVI remained unchanged. In non-HD
      animals both doses of DOB increased LVDP, but only the larger dose increased CI,
      whereas peak SV decreased with the smaller dose. Arterial carbon dioxide tension
      (PaCO2) increased, whereas pH and arterial oxygen tension (PaO2) decreased;
      however, O2DI remained unchanged. Concomitant hemodilution and DOB infusion
      resulted in attenuation of HR response to DOB, exaggerated the drop in MAP and
      SVR, and increased LV dP/dt. Only the larger dose of DOB increased the CI,
      whereas neither dose could alter the SVI in HD animals.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7803745
TI  - Essential thrombocythemia and coronary artery bypass surgery.

PMID- 7803746
TI  - Management of cardiopulmonary bypass in a patient with heparin-induced
      thrombocytopenia using prostaglandin E1 and aspirin.

PMID- 7803747
TI  - One-lung ventilation during video-assisted thoracoscopic ligation of a thoracic
      duct in a three-year-old child.

PMID- 7803748
TI  - Anesthetic management of pediatric patients undergoing thoracoscopy.

PMID- 7803749
TI  - Contralateral lung soiling following laser resection of a bronchial tumor.

PMID- 7803750
TI  - A theoretical evaluation of cost-effectiveness of pulmonary artery catheters in
      patients undergoing coronary artery surgery.

PMID- 7803752
TI  - Pro: perioperative ischemia is benign.

PMID- 7803751
TI  - Kenneth K. Keown, MD: pioneer of cardiac anesthesiology.
AB  - In 1948, just 2 years out of his anesthesiology residency at Hahnemann Medical
      College and Hospital, Kenneth K. Keown, MD, was chosen as the anesthesiologist
      for the procedure that launched the era of intracardiac surgery--a mitral valves
      commissurotomy. Although surgery on stenotic mitral valves had met with some
      success as early as the 1920s, its application had lain dormant for some 25
      years. In effect, Keown and Hahnemann's Chief of Thoracic Surgery, Charles P.
      Bailey, MD, who performed the daring operation, launched the acceptance of
      intracardiac procedures, showing that the heart could be invaded with a
      successful outcome. Keown and Bailey continued as a team through many innovative
      cardiac procedures, during which Keown wrote the first monograph on cardiac
      anesthesia in 1956. Keown was also an early innovator in perfecting methods of
      inducing hypothermia in cardiac surgery and is also renowned for his pioneering
      work in cardiac arrhythmias, using lidocaine to counteract fibrillation during
      cardiac surgery. In 1957, Keown returned to his home state of Missouri to build a
      department of anesthesiology at the University of Missouri School of Medicine. He
      advocated allowing only physicians trained in the specialty to administer
      anesthesia, and he believed firmly that anesthesiology should be a freestanding
      specialty separate from surgery. He also maintained a vigorous resident
      recruitment service. Keown held leadership positions in many medical
      organizations and, during a sabbatical from Missouri, served on the hospital ship
      Hope in Tunisia. He was Professor and Chief, and later Chairman, Section of
      Anesthesiology, at the University of Missouri Medical Center, and from 1969 until
      his death in 1985, he also served as the Center's Medical Director.

PMID- 7803753
TI  - Con: intraoperative myocardial ischemia is not benign.
AB  - The principal importance of intraoperative ischemia is its consistent association
      with adverse outcome. In coronary artery surgery the finding of prebypass
      ischemia is an important predictor, and postbypass ischemia is a critical
      predictor of adverse outcome. One in three patients with postbypass ischemia will
      suffer an adverse outcome in CABG. Furthermore, prevention of postbypass ischemia
      may improve outcome in CABG. Clearly, intraoperative ischemia in CABG surgery is
      an ominous sign that should be regarded with the utmost concern by
      anesthesiologists. In noncardiac surgery, intraoperative ischemia also indicates
      about a one in three chance of adverse outcome. Although it is less sensitive
      than postoperative ischemia, it may have superior positive predictive power and
      specificity. Most importantly, intraoperative monitoring for ischemia is
      currently available to most patients, whereas extended postoperative monitoring
      is not. The finding of intraoperative ischemia defines a high-risk group of
      patients who may merit special monitoring and treatment. To regard intraoperative
      ischemia as benign would be inconsistent with available information.

PMID- 7803754
TI  - An abnormal arterial pressure tracing.

PMID- 7803755
TI  - Incorrectly labelled double-lumen tube.

PMID- 7803756
TI  - Response: complaint on Mallinckrodt broncho-cath endobronchial tube.

PMID- 7803757
TI  - Another complication of pulmonary artery catheter usage.

PMID- 7803758
TI  - Attenuation of vagal reflexes during tracheal intubation following vagotonic
      anesthetic agents.

PMID- 7803759
TI  - Introduction: protein kinases in signal transduction.

PMID- 7803760
TI  - The Raf-1 serine/threonine protein kinase.
AB  - Raf-1 belongs to a family of serine/threonine protein kinases which are highly
      conserved through evolution in multicellular organisms. Raf-1 kinase has gained
      much attention due to its function as a critical shuttle enzyme that connects
      stimulation of growth factor receptors and protein kinase C at the cell membrane
      to changes in the expression of genes involved in the control of cell growth,
      differentiation and survival. Regulation of Raf-1 activity is complex and
      involves Ras, as well as several serine/threonine and tyrosine kinases. Through a
      series of phosphorylation events, extracellular signals are connected through the
      Raf-1/MAP kinase pathway to activity-regulation of several oncogene-class
      transcription factors via phosphorylation of specific serine residues. Under
      ordinary circumstances, the cascade involving Raf-1 eventually leads to changes
      in gene expression and protein synthesis. Upon constitutive activation of Raf-1
      kinase, as a result of genetic changes, a variety of cell types acquire a
      transformed phenotype.

PMID- 7803761
TI  - p70s6k/p85s6k: mechanism of activation and role in mitogenesis.
AB  - The p70s6k/p85s6k represent two isoforms of the same kinase which are derived by
      differential splicing from a common gene. The p85s6k isoform is identical to
      p70s6k except for a 23 amino acid extension at its N-terminus, which
      constitutively targets it to the nucleus. Both isoforms are activated by
      multisite phosphorylation in response to mitogens and reside on the same
      signaling pathway, a pathway which is distinct from that of p42mapk/p44mapk
      pathway. Inhibitory p70s6k/p85s6k antibodies or the immunosuppressant rapamycin
      selectively inhibit kinase activity and repress or abolish cell growth depending
      on the inhibitory agent employed and the cell type examined. Recent studies imply
      that these effects are exerted through inhibition of 40S ribosomal protein S6
      phosphorylation, the kinase target, which in turn suppresses the translation of a
      family of transcripts essential for cell growth.

PMID- 7803762
TI  - The mitogen-activated protein kinases, ERK1 and ERK2.
AB  - The MAP kinases are ubiquitous enzymes that are activated in a complex fashion
      and inactivated by multiple phosphatases including a dedicated dual specificity
      enzyme. These kinases have a diverse array of substrates with important functions
      that result in their substantial regulatory impact. The ERK/MAP kinase cascade
      displays not only downstream but also upstream interactions as well as cross talk
      with other signaling pathways which fine tunes the cascade in a cell type
      specific fashion. Transforming agents utilize this cascade in inducing cell
      proliferation.

PMID- 7803763
TI  - Regulation and functions of the glycogen synthase kinase-3 subfamily.
AB  - Glycogen synthase kinase-3 is a 'black sheep' among protein kinases. Although its
      name suggests a primary function in intermediary metabolism, its scope is far
      more diverse as indicated by both genetic and biochemical evidence. Over the past
      five years the enzyme has emerged as an important component of transduction
      pathways ultimately regulating cell fate and differentiation. The molecular
      mechanisms underlying these functions are only just being unraveled but point to
      a novel mode of cellular regulation conserved in all eukaryotes.

PMID- 7803764
TI  - Protein kinase C--an enzyme and its relatives.
AB  - Protein kinase C (PKC) is the major target for tumor-promoting phorbol esters in
      mammalian cells and a key mediator in signaling via phospholipid hydrolysis. The
      existence of at least 10 structurally related enzymes comprising the PKC family
      and their differential expression in mammalian tissues raises the obvious
      question, what functions do the members of this enzyme family fulfil in normal
      and malignant cell growth? Although there is a host of experimental approaches
      and observations relating to this question, the challenge remains to define the
      roles of individual PKC enzymes in various physiological responses.

PMID- 7803765
TI  - The cAMP-dependent protein kinases and cAMP signal transduction.
AB  - The cAMP signal transduction system is one of several second messenger-dependent
      pathways that generates intracellular responses to extracellular signals. The
      primary element in this cascade is the cAMP-dependent protein kinases (PKA),
      which mediate most cAMP actions by phosphorylation. Regulatory subunit isoforms
      bind cAMP and localize catalytic subunit isoforms near substrate proteins. C
      subunit isoforms also may have specific roles in PKA function. Compared to the C
      alpha-subunit isoform, C gamma has a more limited distribution, a different
      substrate and inhibitor specificity, and appears to require higher levels of cAMP
      for activation. Many PKA isoforms with differing localization, regulatory, and
      kinetic properties are thus possible. The potential roles for R- and C-subunits
      are discussed in the broad context of cAMP/PKA-mediated cell function.

PMID- 7803766
TI  - Calcium/calmodulin-dependent protein kinases.
AB  - Ca2+ is widely recognized as an essential intracellular second messenger in
      eukaryotic systems regulating processes such as muscle contraction,
      neurotransmitter release, gene expression and cell proliferation. The effects of
      Ca2+ are frequently mediated via interaction with calmodulin (CaM) and strong
      evidence indicates, in turn, that the effects of Ca2+/CaM are often achieved
      through the regulation of protein phosphorylation. A family of CaM-dependent
      protein kinases has been identified that includes: myosin light chain kinase,
      phosphorylase kinase, CaM kinase I, CaM kinase II, EF-2 kinase (CaM kinase III)
      and CaM kinase IV. The structure, regulation and function of this important
      family of second messenger-regulated protein kinases will be briefly reviewed.

PMID- 7803767
TI  - The cell cycle kinases.
AB  - This review summarizes our current knowledge of the regulation of the cell cycle
      by the cyclin-dependent kinase family (CDK). The CDKs are regulated both by
      binding their cyclin partners, and by phosphorylation of certain key residues.
      Cyclin synthesis and destruction are regulated during the cell cycle, and there
      are two broad classes of cyclins: the START or G1 cyclins, and the mitotic or G2
      cyclins. In vivo the different cyclins and CDKs demonstrate a high degree of
      specificity in binding to each other, and it appears that specific cyclin-CDK
      complexes are involved in the regulation of particular cell cycle events.

PMID- 7803768
TI  - [Radiological findings in lung transplantation].
AB  - Lung transplantation (single-lung transplantation, double-lung transplantation or
      heart-lung transplantation) may be the only effective therapy in end-stage
      pulmonary disease. At specialized institutions it has been performed on a routine
      basis for some years now. Diagnostic imaging plays an important role in the
      assessment of potential recipients as well as for the postoperative evaluation
      after transplantation. The aim of this review is to describe the role of imaging
      procedures of the chest in these patients and to demonstrate characteristic plain
      radiographic and computed tomographic findings. Normal postoperative findings
      specific to lung transplant patients as well as typical complications are
      presented. These include reimplantation response, acute and chronic rejection,
      and the typical bacterial, viral, and fungal infections as well as the sequelae
      of transbronchial biopsy.

PMID- 7803769
TI  - [Somatostatin receptor scintigraphy in endocrine orbitopathy].
AB  - Somatostatin receptor scintigraphy with 111In-labeled octreotide proves to be a
      very sensitive diagnostic tool for evaluation of inflammative activity in
      endocrine ophthalmopathy (EO). The results of somatostatin receptor scintigraphy
      (SRS) in 40 patients with EO show a high orbital accumulation of 111In-octreotide
      in clinically active EO (4 h-median/orbit-brain-ratio: 12.6; controls 4 h-median:
      5.8) Patients with clinically inactive EO (4 h-median: 7.1) show a similar
      orbital accumulation of radioactivity compared to controls. 5 patients with
      active orbital myositis also revealed an even higher orbital accumulation of
      radioactivity (4 h-median: 42.3). The diagnostic value of SRS lies in its ability
      to act as a measure of inflammation and can be useful as an activity parameter
      when planning therapeutic procedure as well as for EO follow-up. The results in
      patients with orbital myositis nevertheless do not permit a differential
      diagnosis with this method. The therapeutic value of 111In-octreotide in Graves'
      disease has yet to be established.

PMID- 7803770
TI  - [Cerebral arteriovenous angiomas: 3-dimensional demonstration by spiral CT].
AB  - In 20 patients with known or suspected supratentorial arteriovenous
      malformations, an attempt was made to see how far CT angiography with 3
      dimensional reconstructions is able to make a diagnosis and to differentiate the
      various components of the angioma. Spiral CT was performed following an
      intravenous bolus injection of 60-80 ml of iodine containing contrast medium. In
      all patients the diagnosis was confirmed by intra-arterial DSA of the vertebral
      vessels. In 13 patients, av malformations could be diagnosed following
      multiplanar 3-D reconstructions which agreed with the findings on DSA. The large
      supplying vessels, the nidus and the large draining veins could be defined with
      certainty. In 6 patients follow-up examination after embolisation was performed.
      The results could be demonstrated in three dimensions and the success of
      treatment could be documented unequivocally. CT angiography with 3-D
      reconstruction is able to supply important information in the majority of
      intracranial av malformations, both during initial investigation and following
      treatment.

PMID- 7803771
TI  - [Spiral computerized tomography of the breast].
AB  - AIM: To evaluate the use of spiral CT in the diagnosis of breast lesions.
      MATERIAL AND METHODS: 93 female patients with suspicious or uncertain
      mammographic findings were examined by CT before and after contrast enhancement
      according to the following practical method: table movement, 6 mm/s, slice
      thickness 6 mm, increment 4 mm, contrast 200 ml, injection rate 3 ml/s, scan
      start 50 s after the beginning of the injection. Histological confirmation was
      present in 85 patients. RESULTS: All 44 invasive carcinomas were recognised. They
      were characterised by intensive focal contrast uptake. Only 2 out of 7
      intraductal carcinomas were not shown by CT. 36 out of 38 benign lesions were
      correctly diagnosed. 2 out of 11 fibroadenomas showed strong enhancement and were
      incorrectly diagnosed. The examinations provided valuable additional information
      compared to mammography and sonography. CONCLUSION: Spiral CT is very useful for
      elucidating problems in the diagnosis of breast lesions. Its advantages consist
      in the speed of the method, comfort for the patient, absence of movement
      artifacts, easy standardisation and wide applicability.

PMID- 7803772
TI  - [Detection of coronary calcification by ultrafast CT compared with coronary
      angiography].
AB  - The angiographical findings of 24 patients with coronary artery disease were
      compared with qualitative and quantitative detection of coronary calcification by
      ultrafast CT. Doubts concerning the capabilities of the ultrafast CT for a
      screening of coronary artery disease arise when the results of one third false
      positive and false negative findings are considered. Variations in the
      quantification of coronary calcification were too great to allow a realistic
      assessment of the degree of stenosis of the coronary arteries.

PMID- 7803773
TI  - [Fluoroscopically guided percutaneous fine-needle biopsy of the lung using the
      ROTEX needle: results in 890 patients with focal lung lesions].
AB  - Fluoroscopically guided transthoracic fine needle biopsies were performed in 890
      patients (380 female, 582 male, mean age: 56 years). In 795 patients (89.4%) the
      first biopsy was successful. The success rate of biopsy correlated closely with
      the size of the lesion and increased with larger size. Sensitivity in the
      diagnosis of malignant lesions was 94.6%, specificity 99.5%. Due to cytological,
      histological, and clinical confirmation of benign lung lesions in 300 patients
      (33.7% of all patients), the number of unnecessary diagnostic thoracotomies for
      benign disease could be reduced significantly. In 9 of 113 cases (8%)
      histological reclassification of the cytologic results was necessary.
      Reclassification was not necessary in the differentiation between benign and
      malignant lesions and between small cell and non-small cell carcinomas. The
      overall complication rate was 24.7% (220 patients). Only 36 patients (4% of all
      patients) required chest-tube insertion. There were no fatal complications.
      Percutaneous fluoroscopically guided transthoracic fine needle biopsy of the
      lung, performed with the Rotex needle, is a time-effective, safe, and efficient
      method for diagnosing focal pulmonary lesions.

PMID- 7803774
TI  - [Evaluation of rapid gradient-echo and turbo-spin-echo sequences in MRT of focal
      liver lesions using 0.5 tesla].
AB  - The value of rapid T1- and T2-weighted fast field (T1-FFE, T2-FFE) gradient-echo
      sequences and T2 weighted turbo-spin echo (TSE) sequences in the diagnosis of
      focal liver lesions using 0.5 Tesla was compared with conventional spin-echo
      sequences (SE). Amongst 88 liver lesions T1-SE sequences showed 98%, T2-TSE
      sequences showed 92%, T2-SE sequence showed 84%, T1-FFE sequence showed 78% and
      T2-FFE sequence showed 69%. Direct comparison has shown that TSE sequences are
      able to demonstrate significantly more lesions (p < 0.05) than T2-SE sequences.
      Quantitative assessment has shown that the tumor/liver contrast/noise ratio in
      the T1-SE sequence was 118% higher than in the T1-FFE sequence (p < 0.001).
      Comparison of T2 weighted sequences has shown that the tumour/liver
      contrast/noise ratio was 45% higher in the TSE sequence than in the T2-SE and
      239% higher than in the T2-FFE sequence (p < 0.001). The results indicate that
      the TSE sequence should be used instead of the conventional T2-SE sequence
      because of the reduced time (about 40%), due to improved image quality and
      increased demonstration rate of liver lesions. Neither T1-FFE nor T2-FFE are
      suitable, when using moderate field strength, to replace T1-SE or TSE sequences.

PMID- 7803775
TI  - [Accuracy of CT angiography in the diagnosis of renal artery stenosis].
AB  - Spiral CT in the form of CT angiography (CTA) provides a new method for the
      investigation of the large vessels. 52 patients with suspected renovascular
      hypertension were examined by CTA and arterial DSA. The computer tomographic and
      angiographic findings in 124 renal arteries were compared. Sensitivity of CTA for
      demonstrating renal artery stenosis was 95%, and for relevant stenoses it
      actually reached 100%. Specificity was 92%. Positive/negative prediction value
      was 85% and 100%. CTA proved outstandingly good for demonstrating or excluding
      renal artery stenosis and was superior to other imaging methods in several
      respects. CTA requires high contrast values, optimal timing and careful
      evaluation. Amongst various forms of image reconstruction, interactive viewing of
      the primary axial images and multiplanar reconstruction in a cine mode are
      essential and MIP projections are valuable.

PMID- 7803776
TI  - [MRT diagnosis of recurrence of gynecologic tumors].
AB  - Because of the differences in the signals from recurrent tumours and fibrosis
      during MRT, this method is highly suitable for differentiating between recurrent
      gynaecological tumours and scar formation. The value of MRT in investigating
      suspected recurrences was studied in 27 patients aged between 34 and 83 years. It
      was possible to distinguish between recurrent tumour with its high intensity
      signal from low signal fibrosis, using T2-weighted spin echo sequences in all
      cases. By means of multiplanar reconstruction and because of its high soft tissue
      contrast it was possible to determine the extent of tumour growth and
      differentiate it from surrounding tissues. With a sensitivity of 90%, specificity
      of 100% and accuracy of 92%, MRT is superior to all other imaging methods,
      including CT, in the diagnosis of tumour recurrence.

PMID- 7803777
TI  - [Sclerotherapy of the internal spermatic vein in varicocele. Significance of
      normal anatomical variants].
AB  - During a period of four years, 386 patients with left sided varicoceles were
      treated by sclerotherapy of the left internal spermatic vein. This was successful
      in 93.8%. The most common complication was perforation of the vein in 6.2%.
      Technical success and complications depended on anatomical variations. Of
      particular significance was Bahren type IVb (competent main vein, incompetent
      collaterals) which occurred in 18.9%. This accounted for 66.5% of all
      perforations and 54.2% of unsuccessful interventions. The recurrence rate was
      3.8%.

PMID- 7803778
TI  - [Significance of intravascular ultrasound in arteriosclerotic calcified intima
      plaques: in vitro comparison of 20 and 12.5 MHz transducers].
AB  - The aim of this in vitro study was to analyze the diagnostic performance of
      intravascular ultrasound (IVUS) in vessel wall calcifications and to compare the
      accuracy of mechanical 12.5 and 20 MHz transducers. Fourty-three sections of 10
      vessels with signs of arteriosclerotic disease on pathologic examination were
      examined. Slices 500 microns thick were obtained and examined radiographically at
      9 fold magnification. In each section, identical segments were defined, amounting
      to a total of 344 segments. The IVUS sections were analyzed by 3 experienced
      readers. For statistical evaluation ROC analysis was performed using
      magnification radiography as a reference. An area under the curve (AUC) of 0.79
      was obtained for the 12.5 transducer and of 0.83 for the 20 MHz transducer.
      Additionally, sensitivity, specificity, and accuracy were determined. Sensitivity
      depended on the morphology, size, and density of the calcified lesions. We
      therefore conclude that the sensitivity of intravascular ultrasound concerning
      calcified arteriosclerotic plaques is limited and that there is no significant (p
      < 0.01) difference between mechanical 20 and 12.5 MHz transducers in examining
      iliac arteries.

PMID- 7803779
TI  - [Evidence of fluoride-induced effects on the calcaneus by measurements of
      broadband ultrasound attenuation (BUA)].
AB  - We measured broadband ultrasound attenuation (BUA) of the calcaneus as well as
      radial (RBD) and spinal bone density (SBD) in normal and osteoporotic females (n
      = 188) both before treatment and after long-term fluoride therapy. RBD was
      measured using single photon absorptiometry of the non-dominant distal forearm
      (SPA) and spinal bone density (SBD) was assessed using quantitative CT (QCT). In
      untreated osteoporotic patients (n = 62), BUA as well as the other densitometric
      methods showed significantly lower values (p < 0.05) when compared to age matched
      controls (n = 75). Females with osteoporosis and long-term treatment with
      fluoride (n = 51) had both significantly higher BUA values and higher spinal bone
      density when compared to women with untreated osteoporosis. BUA and SBD were
      correlated in the entire group (r = 0.5, r < 0.0001) as well as in the subgroups
      of untreated (r = 0.48, p < 0.001) and fluoride-treated patients with
      osteoporosis (r = 0.4, p < 0.05). These results suggest that BUA provides further
      evidence of an osteogenic response to fluoride at peripheral weight-bearing
      skeletal sites such as the calcaneus.

PMID- 7803780
TI  - [Comparison of the value of angioscopy, angiography and ultrasonography in
      detection of pathologic vascular processes].
AB  - AIMS: The ability of angioscopy, angiography and sonography to evaluate
      arteriosclerotic vascular lesions were compared to determine if angioscopy is a
      valuable addition in the diagnostic armamentarium. METHODS: An in-vitro study was
      selected to enable microscopic assessment of the arteries. Angiography was
      followed by sonography and endoscopy and finally the vessels were evaluated macro
      and microscopically. RESULTS: The configuration of the vascular stenosis (plaque
      shape, semicircular-eccentric, circular-concentric) was more reliably defined
      with angioscopy as compared to angiography and sonography. Intense calcification
      of plaque was detected sonographically with a high sensitivity (90%) using the
      acoustic shadowing and high amplitude criteria. Angioscopy was superior in
      differentiating between simple and complicated plaques and the assessment of
      ulcerations, while the visualization of the entire vascular tree with potential
      collaterals remained the domain of angiography. CONCLUSIONS: Angioscopy seems to
      be valuable addition in the evaluation of arterial vascular disease. It can be
      used in the quality control after interventional radiology and surgery.

PMID- 7803781
TI  - CT appearance of omental torsion: fat spiral pattern.

PMID- 7803782
TI  - Three cases of non-tumoural tight stenosis of the bifurcation of the hilar bile
      ducts.
AB  - Stenosis of the bifurcation of the hepatic bile duct is usually caused by
      malignant lesion. We report on three different causes of benign stenosis of the
      hepatic confluence with a similar radiological pattern on direct cholangiography.
      The first case is considered a spontaneous neuroma, the second a periductal
      abscess, and the third case a postoperative stricture Bismuth type 4.

PMID- 7803783
TI  - [Intestinal strongyloidiasis and isosporiasis in AIDS].

PMID- 7803784
TI  - [Pelvic lipomatosis as a "natural contrast medium" in digital radiography of the
      small pelvis].

PMID- 7803785
TI  - MR imaging of primary muscular sarcoidosis. Case report.

PMID- 7803786
TI  - CD30 (Ki-1) molecule: a new cytokine receptor of the tumor necrosis factor
      receptor superfamily as a tool for diagnosis and immunotherapy.

PMID- 7803787
TI  - Characterization of three erythropoietin (Epo)-binding proteins in various human
      Epo-responsive cell lines and in cells transfected with human Epo-receptor cDNA.
AB  - Molecular cloning of a cDNA for a mouse erythropoietin (Epo) receptor (EpoR) has
      facilitated the understanding of the structure of this receptor. However, there
      is, as yet, no explanation for the discrepancy between the protein recognized by
      specific antibodies against mouse EpoR and the unexpectedly larger species that
      can be cross-linked to labeled Epo. It is unclear whether the product of an
      unidentified gene is included in the EpoR complex. In the present study, we
      directly compared the cross-linking patterns for human EpoR that were
      endogenously expressed in three types of Epo-responsive cell, and that was
      artificially expressed in nonhematopoietic cells after transfection with cDNA for
      human EpoR. We observed that 85-kD and 105-kD proteins formed ligand-receptor
      complexes in all the human Epo-responsive cells and, furthermore, that the
      formation of a complex derived from the 70-kD protein was dependent on the level
      of expression of the cloned EpoR mRNA in these cells. By contrast, a prominent
      cross-linked band derived from the 70-kD protein and a weaker band derived from
      the 80- to 85-kD protein, but no band derived from the 105-kD protein, could be
      shown in the case of nonhematopoietic cells transfected with the human EpoR cDNA.
      These observations suggest that the cloned cDNA for human EpoR alone does not
      allow generation of the complete EpoR in nonhematopoietic cells and that the 105
      kD Epo-binding protein may represent the product of an as yet unidentified gene
      that is expressed in hematopoietic cells.

PMID- 7803788
TI  - Inhibiting interleukin-1 and tumor necrosis factor-alpha does not reduce
      induction of plasminogen activator inhibitor type-1 by endotoxin in rats in vivo.
AB  - In experimental animals and humans, intravenous (i.v.) injection of endotoxin
      induces large increases in circulating plasminogen activator inhibitor type-1
      (PAI-1), a major inhibitor of blood fibrinolysis. A similar increase is seen
      after the injection of interleukin-1 (IL-1) or of tumor necrosis factor-alpha
      (TNF-alpha), suggesting that these cytokines mediate the induction, by endotoxin,
      of PAI-1. To test this hypothesis we pretreated rats, before i.v. endotoxin, with
      compounds that inhibit the formation of cytokines (pentoxifylline;
      dexamethasone), or with compounds that inhibit the action of these cytokines
      (anti-TNF antiserum for TNF-alpha; IL-1 receptor antagonist for IL-1). None of
      these pretreatments affected the induction of PAI-1 synthesis by endotoxin.
      However, pretreatment did reduce the endotoxin-induced increase in plasma tPA
      antigen concentration. Thus, the data suggest that, in rats in vivo, TNF-alpha
      and IL-1 are not significantly involved in the induction of PAI-1 by endotoxin.

PMID- 7803789
TI  - Mechanism of antithrombin III inhibition of factor VIIa/tissue factor activity on
      cell surfaces. Comparison with tissue factor pathway inhibitor/factor Xa-induced
      inhibition of factor VIIa/tissue factor activity.
AB  - Recent studies have shown that antithrombin III (AT III)/heparin is capable of
      inhibiting the catalytic activity of factor VIIa bound either to relipidated
      tissue factor (TF) in suspension or to TF expressed on cell surfaces. We report
      studies of the mechanism of which by AT III inhibits factor VIIa bound to cell
      surface TF and compare this inhibitory mechanism with that of tissue factor
      pathway inhibitor (TFPI)-induced inhibition of factor VIIa/TF. AT III alone and
      AT III/heparin to a greater extent reduced factor VIIa bound to cell surface TF.
      Our data show that the decrease in the amount of factor VIIa associated with cell
      surface TF in the presence of AT III was the result of (1) accelerated
      dissociation of factor VIIa from cell surface TF after the binding of AT III to
      factor VIIa/TF complexes and (2) the inability of the resultant free factor VIIa
      AT III complexes to bind effectively to a new cell surface TF site. Binding of
      TFPI/factor Xa to cell surface factor VIIa/TF complexes markedly decreased the
      dissociation of factor VIIa from the resultant quaternary complex of factor
      VIIa/TF/TFPI/factor Xa. Addition of high concentrations of factor VIIa could
      reverse the AT III-induced inhibition of cell surface factor VIIa/TF activity but
      not TFPI/factor Xa-induced inhibition of factor VIIa/TF activity.

PMID- 7803790
TI  - Identification of 15 different candidate causal point mutations and three
      polymorphisms in 19 patients with protein S deficiency using a scanning method
      for the analysis of the protein S active gene.
AB  - To screen for point mutations causing protein S deficiency, we used a sequence of
      techniques specifically for the study of the protein S active gene, PS alpha.
      This strategy comprises amplification of exons and intron/exon junctions by means
      of the polymerase chain reaction (PCR) and electrophoresis of the amplified
      fragments in polyacrylamide gel containing a gradient of denaturing agents
      (denaturing gradient gel electrophoresis). Only fragments with altered melting
      behavior are sequenced after asymmetric PCR. Beside the frequent polymorphism
      already described on Pro 626, we detected 18 different sequence variations by
      studying exons II, IV, V, VIII, X, and XV in 19 of 100 consecutive patients with
      protein S deficiency. Fifteen were candidate causal mutations, 4 of which were
      associated with a qualitative deficiency (type IIa or IIb). The remaining three
      sequence variations were probably polymorphisms.

PMID- 7803791
TI  - Interleukin-2-transduced lymphocytes grow in an autocrine fashion and remain
      responsive to antigen.
AB  - The maintenance of T lymphocytes in vivo after adoptive transfer for
      immunotherapy requires the systemic administration of interleukin-2 (IL-2), but
      prolonged administration of IL-2 is associated with substantial toxicity. The
      constitutive production of IL-2 by T cells may be an alternative method to
      prolong T-cell survival and potentially augment antitumor responses. To study the
      effects of constitutive production of IL-2 on the growth and antigen reactivity
      of a murine T cell, the sperm-whale myoglobin (SWM) specific T-cell line 14.1 was
      retrovirally transduced with the cDNA for IL-2. Cells that were transduced with
      vectors without an internal promoter were able to proliferate in the absence of
      exogenously added IL-2, and to grow in an autocrine fashion. These vectors used
      an internal ribosomal entry site (IRES) to allow translation of the neomycin
      phosphotransferase (neor) gene. In contrast, the cells transduced with an IL-2
      vector in which the neor gene was under the transcriptional control of an
      internal SV-40 promoter failed to proliferate or grow in the absence of
      exogenously added IL-2. The proliferation of the cells growing without IL-2 could
      be inhibited with antibodies to the IL-2 receptor or to human IL-2, indicating
      that they were still IL-2 dependent. Despite their autocrine growth, no tumor
      formation was observed in syngeneic mice injected subcutaneously with the
      transduced cells, and the cells retained their antigen reactivity and
      specificity. These results suggest that autocrine growth of T cells for therapy
      will not interfere with effector function.

PMID- 7803792
TI  - CD3+ leukemic large granular lymphocytes utilize diverse T-cell receptor V beta
      genes.
AB  - CD3+ large granular lymphocyte (LGL) leukemia is a disease of unknown etiology
      characterized by clonal proliferation of T cells that usually express T-cell
      receptor (TCR) alpha beta heterodimers. The purpose of this study was to identify
      the variable (V), joining (J), and diversity (D) region TCR beta-chain genes
      expressed by CD3+ LGL leukemic cells in an attempt to gain insights into the
      etiology of this disorder. Twelve patients with LGL leukemia were studied,
      including seven with both LGL leukemia and rheumatoid arthritis (RA). RA is also
      a disease of unknown etiology that occurs frequently in patients with LGL
      leukemia. Clonally expanded T cells that express specific TCR V beta genes have
      been identified in fluid and tissue specimens from the joints of patients with
      RA. In this study, V beta expression was determined by PCR using a panel of 22
      unique V beta primers to amplify cDNA prepared from peripheral blood mononuclear
      cells (PBMC). A dominant V beta gene product was readily apparent in all
      patients. To confirm that the dominant V beta gene originated from a clonal
      expansion, DNA fragments corresponding to the dominant V beta genes were
      subcloned into plasmids and independently isolated recombinants were sequenced. V
      D-J region sequences that occurred repeatedly indicated clonality. The V beta and
      J beta genes expressed by the leukemic cells showed a pattern of distribution
      that followed the frequency with which these genes are represented in the
      peripheral blood. The residues corresponding to the third complementarity
      determining region of the TCR beta chain were different in all cases. A specific
      pattern of VDJ usage was not identified for those patients with both LGL leukemia
      and RA; however, utilization of V beta-6 by LGL clones (N = 3) was observed only
      in the setting of RA. These data suggest that leukemic CD3+ LGL cells have been
      clonally transformed in a random fashion with respect to the TCR beta chain.

PMID- 7803793
TI  - A translocated erythropoietin receptor gene in a human erythroleukemia cell line
      (TF-1) expresses an abnormal transcript and a truncated protein.
AB  - We previously identified a translocation breakpoint in exon 8 of the
      erythropoietin receptor (EpoR) gene in TF-1 cells, a cell line derived from a
      human erythroleukemia. To investigate the potential pathogenetic significance of
      this abnormality, we more precisely mapped the breakpoint within exon 8 and
      studied the expression of the translocated gene by S1 nuclease mapping of EpoR
      transcripts and chemical crosslinking of labeled erythropoietin (Epo) to TF-1
      cell surface receptors. Transcripts from the abnormal gene were found to be
      highly expressed in relation to normal EpoR transcripts in TF-1 cells. The
      breakpoint predicted by S1 mapping of abnormal EpoR transcripts agreed closely
      with that determined by Southern analysis. Chemical cross-linking of 125I-Epo to
      TF-1 cells showed an abnormal, low-molecular-weight cross-linked species directly
      recognized by anti-EpoR antibodies and present in considerable excess over the
      normal EpoR. Karyotype analysis showed that each of 10 TF-1 cell metaphases had,
      in addition to multiple other alterations, one chromosome 19 with additional
      chromosomal material translocated onto the short arm at 19p13.3, the location of
      the EpoR gene. We conclude that the structurally abnormal EpoR gene in TF-1 cells
      is highly expressed and produces an abnormal protein. We speculate that the
      chromosomal material brought into the EpoR locus by translocation is responsible
      for the high level of expression. We hypothesize that this translocation
      participated in the evolution of the erythroleukemia from which TF-1 cells were
      derived.

PMID- 7803794
TI  - Sequential analysis of 43 patients with non-Hodgkin's lymphoma: clinical
      correlations with cytogenetic, histologic, immunophenotyping, and molecular
      studies.
AB  - Few reports correlating specific cytogenetic abnormalities with distinct subtypes
      of lymphoma have performed serial studies at diagnosis and at tumor recurrence or
      progression. In our file of 325 cytogenetically analyzed non-Hodgkin's lymphoma
      (NHL) patients studied over the past decade, 43 had serial biopsies, 39 of whom
      had at least two successful preparations; of the 43, nine had one and 32 had two
      or more cytogenetically abnormal specimens. In this study, we correlated
      cytogenetic, histopathologic, molecular, and clinical parameters. Patients with
      low-grade lymphomas were as likely as patients with intermediate- or high-grade
      lymphomas to acquire new chromosomal abnormalities with time (16 of 23 patients
      as compared with 7 of 16; P2 = .11, chi 2 test). In four patients, originally
      diagnosed indolent disease progressed to aggressive disease; all had t(14;18),
      all gained additional chromosomal abnormalities with disease progression, and
      three of the four expressed abnormalities associated with disease progression
      and/or short survival: der(18), +7, and/or +12. Cytogenetic results from early
      disease were compared with those obtained later in disease: in the t(14;18)
      group, the most common abnormalities were +7 (eight patients) and der(18) (five
      patients), both seen later in disease. The most common abnormalities in patients
      without t(14;18) were 6q deletions; they were seen in both early and late disease
      and were associated with significantly shorter survivals (P2 = .0014) compared
      with all patients without 6q deletions. Secondary chromosomal abnormalities,
      observed after at least one previous abnormal study, were seen in 19 of 22
      t(14;18) patients and in 11 of 21 patients without t(14;18) and were associated
      with a poor survival (P2 = .13) compared with patients without any secondary
      chromosomal abnormalities. Chromosome 1 abnormalities were seen in almost half of
      the patients and were observed in initial specimens and early in disease as well
      as late in disease and as secondary abnormalities; 1q involvement was more
      frequent than 1p (15 versus eight patients) and was significantly associated with
      poor survival only in patients with intermediate-/high-grade disease; the most
      common breakpoints were 1q21-q22 (nine patients) and 1p36 (six patients).
      Breakpoints at 2q21 and 3q27-q29 were limited to patients with t(14;18) and were
      almost exclusively secondary in nature. Molecular studies in 24 of our patients
      showed discrepancies with the cytogenetic results in only three patients: two had
      t(14;18) but no molecular rearrangements while two patients had no visible
      t(14;18) but were positive for major breakpoint region (MBR) rearrangement. The
      presence of MBR or minor breakpoint cluster (MCR) rearrangement had no apparent
      effect on survival.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7803795
TI  - Clonality in juvenile chronic myelogenous leukemia.
AB  - Juvenile chronic myelogenous leukemia (JCML) is a myeloproliferative disease in
      which morbidity and mortality are primarily caused by nonhematopoietic organ
      failure from myelomonocytic infiltration or by failure of the normal bone marrow.
      Morphologic evidence of maturation arrest, karyotypic abnormalities, and
      progression to blast crisis are infrequent events. Viral infections and other
      reactive processes can initially mimic the clinical course of JCML, creating
      diagnostic problems. Because of the rarity of JCML and technical limitations,
      formal clonality studies have not been reported previously. Nine female JCML
      patients were identified by clinical criteria, characteristic 'spontaneous' in
      vitro cell growth, and negative cultures and titers for various viral agents.
      Peripheral blood and bone marrow samples were obtained at the time of diagnosis
      for cell separation and RNA and DNA isolation. To assess clonality, X-chromosome
      inactivation patterns were evaluated using three different, recently developed
      polymerase chain reaction-based clonality assays. All nine female JCML patients
      showed evidence for monoclonal origin of mononuclear cells at the time of
      diagnosis. Cell separation studies further traced the monoclonal origin back to
      at least the most primitive myeloid progenitor cell. Reversion to a polyclonal
      state was demonstrated after bone marrow transplant and also in one patient
      following treatment with 13-cis retinoic acid. This demonstration of clonality in
      JCML delineates it from the reactive processes and provides a basis for molecular
      genetic strategies to identify causally associated mutations.

PMID- 7803796
TI  - Cyclic guanosine monophosphate-dependent protein kinase is targeted to
      intermediate filaments and phosphorylates vimentin in A23187-stimulated human
      neutrophils.
AB  - The effects of the calcium ionophore, A23187, on human neutrophil activation were
      studied in relation to the signaling mechanism of cyclic guanosine monophosphate
      (cGMP)-dependent protein kinase (G-kinase). Immunocytochemistry demonstrated that
      G-kinase translocated from a diffuse localization in the cytoplasm to the
      cytoskeleton after stimulation with A23187. Over a period of 5 minutes, G-kinase
      was transiently colocalized with the intermediate filament protein, vimentin. At
      3 minutes' stimulation with A23187, colocalization of G-kinase and vimentin was
      predominantly confined to filaments that extended into the uropod. The time of
      colocalization of G-kinase and vimentin was reduced in the A23187-stimulated cell
      from 3 minutes to 1 minute by 8-Br-cGMP. Coincident with colocalization was an
      increase in cGMP levels and transient phosphorylation of vimentin in adhered
      A23187-stimulated cells. Phosphorylation of vimentin was maximal after 3 minutes
      with A23187, and was essentially over at 5 minutes. The time of phosphorylation
      of vimentin was also reduced from 3 minutes to 1 minute when cells were
      preincubated with 8-Br-cGMP and then stimulated with A23187, which suggests that
      cyclic adenosine monophosphate (cAMP)-dependent protein kinase does not
      phosphorylate vimentin in A23187-treated neutrophils. Phosphorylation of vimentin
      was not observed in nonactivated cells treated only with 8-Br-cGMP. The presence
      of the protein kinase C inhibitors, staurosporine or H-7, did not inhibit
      vimentin phosphorylation in A23187-treated cells, which provides supportive data
      that protein kinase C is not the phosphorylating enzyme. These results suggest
      that vimentin and G-kinase are colocalized in a Ca(2+)-dependent manner in
      neutrophils, and that vimentin is transiently phosphorylated by G-kinase in
      response to the colocalization of the two proteins. The transient redistribution
      of compartmentalized G-kinase represents one type of neutrophil activation
      mechanism.

PMID- 7803797
TI  - A new X-linked variant of chronic granulomatous disease characterized by the
      existence of a normal clone of respiratory burst-competent phagocytic cells.
AB  - Chronic granulomatous disease (CGD) is characterized by recurrent infections, and
      is usually associated with a complete inability of phagocytic cells to generate
      superoxide anion (O2-). Rarely, variant forms of CGD have been reported in which
      there is reduced, but detectable, O2- production by phagocytic cells. We describe
      three adult males in two kindreds with a unique form of X-linked cytochrome b558
      deficient (X91-) CGD not previously reported. All three patients had two distinct
      populations of phagocytic cells, with one subset capable of normal respiratory
      burst activity and the other larger subset inactive, as in classic CGD (X91 (0)).
      The respiratory burst activity in neutrophils purified from each patient was
      approximately 10% of normal as determined by O2- production, O2 consumption,
      cytochrome b558 spectroscopy, and membrane oxidase activity using a cell-free
      activation system. In contrast with other patients with X91(-)-variant CGD, the
      unique feature of these patients is the presence of a small but significant
      population (5% to 15%) of circulating neutrophils and monocytes with completely
      normal respiratory burst activity as assessed by nitroblue tetrazolium (NBT)
      reduction and flow-cytometric measurement of dihydrorhodamine oxidation. NBT
      reduction of peripheral blood granulocyte-macrophage progenitor cells also showed
      the presence of a subset of colonies derived from myeloid progenitor cells that
      had normal respiratory burst capabilities. A mosaic XX chromosome karyotype and
      an unstable oxidase complex that might occur during myeloid maturation were both
      excluded as possible explanations. In these families, the molecular defect in the
      gp91-phox gene, which is currently under investigation, appears to prevent
      expression of the gene in the majority of neutrophils, but not in a small subset.
      Our studies suggest that commitment to either a respiratory burst-competent or 
      incompetent phagocytic cell occurs at the level of the myeloid progenitor cell.

PMID- 7803798
TI  - A mutation located at the 5' splice junction sequence of intron 3 in the p67phox
      gene causes the lack of p67phox mRNA in a patient with chronic granulomatous
      disease.
AB  - Chronic granulomatous disease (CGD) is due to a functional defect of the O2(-)
      generating NADPH oxidase of neutrophils. Mutations resulting in CGD have been
      shown to occur in only four genes, thus identifying the main components of the
      oxidase complex, namely the two subunits of a membrane-bound cytochrome b and two
      cytosolic factors of activation of 67 kD (p67phox) and 47 kD (p47phox). The
      present study deals with the biochemical and genetic analysis of the defect in a
      patient suffering from a p67phox-deficient form of CGD. The p67phox deficiency
      was ascertained by immunochemistry and the ability of recombinant p67phox to
      restore NADPH oxidase activity using a cell-free system of oxidase activation.
      The cellular extracts from the proband contained no p67phox protein and no
      p67phox mRNA when assayed by Western and Northern blot analysis. However, reverse
      transcription of mRNA and subsequent cDNA amplification by polymerase chain
      reaction using specific p67phox primers showed that trace amounts of a p67phox
      mRNA deleted for exon 3 were synthesized in the patient immortalized B
      lymphocytes. Sequence analysis of the genomic DNA showed a T-to-C transition at
      position +2 of intron 3. This point mutation in the consensus 5' splice site of
      the intron 3 was probably responsible for lack of accumulation of mRNA and also
      for the skipping of exon 3 detected in the few mRNA molecules that escaped
      cellular degradation.

PMID- 7803799
TI  - A deletional frameshift mutation in protein 4.2 gene (allele 4.2 Lisboa)
      associated with hereditary hemolytic anemia.
AB  - We studied a 26-year-old Portuguese patient with recessively transmitted
      hereditary hemolytic anemia. Protein 4.2 was absent from red cell ghosts by
      Western blotting. Although the 4.2 mRNA was not detected in Northern blots, it
      was shown to be present by a procedure based on nested reverse transcription
      polymerase chain reaction (RT-PCR). Partial nucleotide sequencing disclosed a one
      nucleotide deletion at nt 264 (or 265): AAG GTG-->AAG TG, in codon 88 (or 89)
      belonging to exon 2. This change, defining allele 4.2 Lisboa, placed in frame the
      nonsense triplet that normally overlaps codons 136 and 137 (GTG ACC). This
      mutation, which abolishes an EcoNI site, was also found in the gene of the
      proband (homozygous state), her parents, and her brother (heterozygous state).
      Apart from anemia, the patient was free of clinical manifestations. Platelet
      membranes were also investigated using Western blots. Antibodies to red cell
      protein 4.2 showed a doublet (72 and 70 kD) both in the controls and the patient.
      This finding raises an interesting question concerning the relationship between
      this doublet and erythroid protein 4.2.

PMID- 7803800
TI  - Glucose-6 phosphate dehydrogenase mutations and haplotypes in various ethnic
      groups.
AB  - Mutations that produce glucose-6-phosphate dehydrogenase (G6PD) deficiency have
      been identified in samples from patients with hemolytic disease in the United
      States, and in G6PD-deficient samples from Greece, the Canary Islands, the Czech
      and Slovak Republics, South China, and in samples from the Coriell Cell
      Repository. Eight new mutations are described. Particularly unusual were a
      nonsense mutation ("G6PD Georgia"1284A), a deletion of six bases ("G6PD Stony
      Brook" 724-729 del) coding for two amino acids, and a deletion of the invariant
      dinucleotide ApG at the 3' acceptor splice site in the highly conserved sequence
      between intron 10 and exon 11 ("G6PD Varnsdorf"). In addition, five new missense
      point mutations were identified: "G6PD Cleveland"820A creates a deduced AA 274
      Glu-->Lys; "G6PD West Virginia"910T AA 303 Val-->Phe; "G6PD Fushan"1004A, AA 335
      Ala-->Asp; "G6PD Olomouc"1141C AA 381 Leu-->Phe; and "G6PD Praha"1166G AA 389 Glu
      ->Gly. All of the new mutations except for "G6PD Fushan"1004A were found in
      patients with hereditary nonspherocytic hemolytic anemia. A coincidental finding
      in the case of G6PD "West Virginia" was a C-->T transition at nucleotide 1,191.
      This silent mutation, Asn-->Asn, appears to be rare. Haplotype analysis of
      mutations in samples from the Canary Islands and South China agreed with previous
      findings.

PMID- 7803801
TI  - Primary structure of human erythrocyte nicotinamide adenine dinucleotide
      phosphate (NADP[H])-binding protein FX: identification with the mouse tum-
      transplantation antigen P35B.
AB  - Human erythrocytes contain a nicotinamide adenine dinucleotide phosphate
      (NADP[H])-binding protein, FX, whose levels are significantly increased in
      erythrocytes from glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals
      bearing the mediterranean variant of G6PD. Elucidation of the still unknown
      biologic functions of FX was approached by means of amino acid sequencing of its
      25 tryptic peptides. Searching in the EMBL data bank allowed identification of
      extensive homology between these tryptic peptides and all sequence-aligned
      regions encompassing the complete structure of a putative protein encoded by the
      P35B gene in the mouse. This gene, which differs from the normal allele by a
      point mutation, has been previously cloned from a tum- variant of the murine
      tumor cell line P815, so defined because it is associated with low tumorigenicity
      compared with the progenitor P815. The reported P35B cDNA contains an open
      reading frame (ORF) of 813 bp and encodes a putative protein of 271 amino acids
      (30 kD), whereas FX protein is 320 amino acids in length (35.81 kD, in good
      agreement with previous studies). However, a single base shift at position 4,752
      of the P35B gene suppresses the stop codon after Phe 271 and allows continuation
      of the ORF for up to 320 amino acids to reach the same length as FX. The
      remarkably high extent (92%) of homology indicates that erythrocyte FX protein is
      the human homolog of the P35B gene product.

PMID- 7803802
TI  - Long-term outcome of aplastic anemia in adults treated with antithymocyte
      globulin: comparison with bone marrow transplantation.
AB  - The outcome of 155 adult aplastic anemia (AA) patients treated with antithymocyte
      globulin (ATG, Upjohn, Kalamazoo, MI) at University of California, Los Angeles
      from 1977 to 1988 was evaluated. The median survival of the 146 patients who did
      not undergo bone marrow transplantation was 5.6 years, with 49% +/- 4% surviving
      more than 6 years. The most important predictor of survival was positive response
      to ATG (P < 0.001), which was observed in 48% of patients. Among pretreatment
      variables, disease severity was the best predictor of survival. Patients with
      moderate AA (MAA) had significantly better survival than those with severe (SAA)
      or very severe (VSAA) disease (P = 0.04). The 6-year actuarial survival rates of
      the three groups were 71% +/- 9%, 48% +/- 7% and 38% +/- 7%, respectively. Cox
      regression analysis found disease severity to be the only pretreatment variable
      significantly associated with survival (P = .02). Patient age, sex, disease
      etiology, concurrent treatment with androgens, or duration of ATG therapy were
      not associated with differences in survival or response to ATG. Late clonal
      hematologic complications (ie, myelodysplasia, acute myelogenous leukemia) were
      observed in 5 of the 77 patients followed for more than 2 years after ATG
      treatment. In addition, one case of non-Hodgkin's lymphoma and three solid tumors
      occurred in the ATG-treated patients. The survival of 56 ATG-treated patients
      with SAA or VSAA between the ages of 16 and 43 did not differ significantly from
      that of 55 adult AA patients who underwent bone marrow transplant (BMT) during
      the same time period (P = 0.6). However, 6-year survival rates improved from 43%
      for patients transplanted before 1984, to 72% for those who underwent BMT between
      1984 and 1989. In contrast, there was no difference in the survival rates of
      patients treated with ATG during these two time periods (46% v 45%,
      respectively). The results suggest a superior long-term outcome for adult
      patients with SAA treated with BMT rather than with ATG alone, using current
      protocols.

PMID- 7803803
TI  - Factor VIII gene rearrangements in severe hemophilia A.

PMID- 7803804
TI  - Unrelated donor marrow transplantation for severe acquired aplastic anemia using
      cyclophosphamide, antithymocyte globulin, and total body irradiation.

PMID- 7803805
TI  - Thrombopoietin from human embryonic kidney cells is the same factor as c-mpl
      ligand.

PMID- 7803806
TI  - Human herpesvirus-6 and bone marrow transplantation.

PMID- 7803807
TI  - Subclinical infection of the respiratory tract of immunocompromised patients by
      human herpesvirus-6.

PMID- 7803808
TI  - Function of the interleukin-2 (IL-2) receptor gamma-chain in biologic responses
      of X-linked severe combined immunodeficient B cells to IL-2, IL-4, IL-13, and IL
      15.
AB  - The interleukin-2 (IL-2) receptor gamma-chain is a common component of several
      members of the cytokine receptor superfamily including those for IL-2, IL-4, IL
      7, IL-9, IL-15, and possibly IL-13, and has recently been renamed the common
      gamma-chain (gamma c-chain). Transfection experiments have shown that the gamma c
      chain participates in signal transduction by IL-2, IL-4 and IL-7, but a
      functional role for the gamma c-chain in biological responses by normal T cells
      and B cells to these cytokines has not been established. In this study, we have
      used X-linked severe combined immunodeficiency (X-SCID) as a naturally occurring
      gamma c-chain gene disruption model to examine the role of the gamma c-chain in
      human B-cell responses to IL-2, IL-4, IL-13, and IL-15. Our experiments show that
      B cells from two X-SCID patients with characterized gamma c-chain gene mutations
      do not respond to IL-2 or IL-15, but respond as well or better than normal B
      cells to both IL-4 and IL-13 in assays for B-cell activation, proliferation, and
      IgE secretion. This finding raises important questions about the function of the
      gamma c-chain in receptors for IL-4 and IL-13, and the nature of the immune
      defect in X-SCID.

PMID- 7803810
TI  - 1st International Conference on Reversal of Multidrug Resistance in Cancer. St.
      Gallen, Switzerland, 1-3 September 1994. Abstracts.

PMID- 7803809
TI  - Erythropoietin and interleukin-3 induce distinct events in erythropoietin
      receptor-expressing BA/F3 cells.
AB  - To compare the signal transduction pathways used by erythropoietin (Ep) and
      interleukin-3 (IL-3), the cDNA for the murine erythropoietin receptor (EpR) was
      introduced into the IL-3-responsive cell lines Ba/F3 and DA-3 using retrovirally
      mediated gene transfer. After selection in G418 and IL-3, clones expressing
      comparable levels of cell surface EpR were identified using biotinylated Ep and
      flow cytometry. A comparison of the effects of Ep and IL-3 on these cells showed
      that most EpR+ Ba/F3 clones, when first exposed to Ep, dramatically increased
      their levels of beta-globin mRNA. The kinetics of appearance of this message
      after exposure to Ep varied considerably from clone to clone, with some clones
      showing a marked increase in beta-globin mRNA within 1 hour, while others
      required several days before an increase was observed. Interestingly, not only
      was this increase not seen with IL-3, but IL-3 prevented the Ep-induced
      appearance of beta-globin message. On the other hand, none of the EpR+ DA-3 cell
      clones tested increased their levels of beta-globin mRNA in response to Ep. While
      the EpR+ DA-3 clones showed identical proliferative responses to IL-3 and Ep,
      most EpR+ Ba/F3 clones displayed a marked, albeit transient, proliferative lag
      when first exposed to Ep. This was manifested as both an increased doubling time
      in liquid culture and a decreased colony size in methylcellulose. Plating
      efficiencies of EpR+ Ba/F3 cells in methylcellulose, however, were identical in
      response to IL-3 and Ep, suggesting that the Ep-induced lag in proliferation
      reflected a growth delay of the entire population of cells to Ep rather than a
      selection of an Ep-responsive subpopulation. Flow cytometric analysis established
      that this growth delay was due to a lengthening of the first G1 period after
      exposure to Ep. Interestingly, this Ep-induced delay in entry into the S phase
      was not detected in cells stimulated with both Ep and IL-3 nor in EpR+ Ba/F3 cell
      clones that did not show an increase in beta-globin mRNA in response to Ep.
      Thymidine-induced growth arrest, however, showed that delaying entry into S phase
      alone was not sufficient to stimulate beta-globin mRNA in the absence of Ep.
      Further studies established that the Ep-induced increase in beta-globin mRNA
      could be inhibited by the tyrosine kinase inhibitor genistein and the protein
      kinase C inhibitor Compound 3.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7803811
TI  - Purification of a 24 kD parasitism-specific hemolymph protein from pharate pupae
      of the Caribbean fruit fly, Anastrepha suspensa.
AB  - We report purification of a 24 kD parasitism-specific protein (24 kD PSP) from
      pharate pupal hemolymph of the Caribbean fruit fly, Anastrepha suspensa, after
      parasitization by the braconid wasp, Diachasmimorpha (= Biosteres) longicaudata.
      We previously utilized isoelectric focusing (IEF) and two-dimensional (2-D) gel
      electrophoresis to demonstrate that the 24 kD PSP consists of two variants with
      pl 6.7 (more abundant) and pl 6.3. Purification of the more abundant 24 kD PSP
      variant was accomplished by Concanavalin A (Con A) sepharose B affinity
      chromatography followed by DEAE column chromatography. A second protocol,
      utilizing wheat germ agglutinin (WGA) sepharose 6MB affinity chromatography
      between the ConA and DEAE chromatographic steps, resulted in the purification of
      a partially deglycosylated form of the 24 kD PSP which retained its
      immunoreactivity with anti-PSP serum but which exhibited a greater relative
      migration in sodium dodecyl sulfate (SDS)-PAGE than the pl 6.7 24 kD PSP variant.
      For structural studies both 24 kD PSP variants were purified from whole hemolymph
      by flat bed IEF followed by SDS-PAGE. Peptide cleavage profiles in 1-D SDS-PAGE
      after treatment with BNPS-skatole, CNBr, and endproteinases Lys-C and Asp-N were
      identical for both 24 kD PSP variants. Primary N-terminus sequences of at least
      the first 20 amino acid residues of both variants were identical. A secondary
      sequence of five amino acids residues was detected in both variants at Thr, the
      seventh amino acid residue from the N-terminus of the primary sequence. These
      data indicate that both 24 kD PSPs are glycoforms of a branched, apparently
      homogeneous polypeptide.

PMID- 7803812
TI  - Model sclerotization studies. 3. Cuticular enzyme catalyzed oxidation of peptidyl
      model tyrosine and dopa derivatives.
AB  - Incubation of N-acetyltyrosine methyl ester with cuticular enzymes, isolated from
      the wandering stages of Calliphora sp larvae, resulted in the generation of N
      acetyldopa methyl ester when the reaction was carried out in the presence of
      ascorbate which prevented further oxidation of the o-diphenolic product.
      Enzymatic oxidation of N-acetyldopa methyl ester ultimately generated dehydro N
      acetyldopa methyl ester. The identity of enzymatically produced N-acetyldopa
      methyl ester and dehydro N-acetyldopa methyl ester has been confirmed by
      comparison of the ultraviolet and infrared spectral and chromatographic
      properties with those of authentic samples as well as by nuclear magnetic
      resonance studies. Since N-acetyldopaquinone methyl ester was also converted to
      dehydro N-acetyldopa methyl ester and tyrosinase was responsible for the
      oxidation of N-acetyldopa methyl ester, a scheme for the cuticular phenoloxidase
      catalyzed conversion of N-acetyltyrosine methyl ester to dehydro N-acetyldopa
      methyl ester involving the intermediary formation of the quinone and the quinone
      methide is proposed to account for the observed results. The conversion of N
      acetyldopa methyl ester to dehydro derivative remarkably resembles the conversion
      of the sclerotizing precursor, N-acetyldopamine, to dehydro-N-acetyldopamine
      observed in the insect cuticle. Based on these comparative studies, it is
      proposed that peptidyl dopa derivatives could also serve as the sclerotizing
      precursors for the sclerotization of the insect cuticle.

PMID- 7803813
TI  - Extension of the mitochondrial transporter super-family: sequences of five
      members from the nematode worm, Caenorhabditis elegans.
AB  - The sequences are presented of cDNAs encoding five related proteins from the
      nematode worm, Caenorhabditis elegans. Three of them can be recognised as the
      homologues of the ADP/ATP, phosphate and oxoglutarate/malate carrier proteins
      that have been found in the inner membranes of mitochondria in other species.
      These carrier proteins, and the uncoupling protein from the mitochondria in
      mammalian brown adipose tissue, have common features in their primary and
      secondary structures, and are members of the same protein super-family. Members
      of this super-family have polypeptide chains approximately 300 amino acid long
      that consist of three tandem related sequences of about 100 amino acids. The
      tandem repeats from the different proteins are inter-related, and each repeat is
      probably folded into a common secondary structural motif consisting of two
      hydrophobic stretches of amino acids with the potential to form membrane spanning
      alpha-helices, linked by an extensive hydrophilic region. The common
      characteristic features of this family of proteins are also present in sequences
      of two further proteins, named C1 and C2, encoded in nematode cDNAs, and in four
      published protein sequences from various sources. Neither the transport
      properties nor the subcellular locations of any of this latter group of six
      proteins are known. Therefore, currently the super-family of mitochondrial
      carrier proteins has at least ten different members.

PMID- 7803814
TI  - Construction of a cosmid contig and of an EcoRI restriction map of yeast
      chromosome X.
AB  - We report here the construction of a complete physical map of the chromosome X of
      yeast Saccharomyces cerevisiae. Fragments resulting from partial Sau3AI digestion
      of DNA from a diploid strain derived from S288C were ligated to linearized pWE15,
      a cosmid vector with T3 and T7 promoters. Another library, made in the cosmid
      vector pOU61 cos, that lacks T3 and T7 promoters, was also used as a source of
      target clones. Chromosome-X-specific clones were sorted out by hybridization with
      radiolabelled pulse-field-gel-purified chromosome X as a probe. Then, 254 cosmids
      were ordered by walking from one to another by hybridization with end-specific T3
      or T7 RNA transcripts as probes. The construction was put to the test by
      hybridization with a battery of chromosome X gene markers, that showed that the
      physical map and the genetic map were colinear. The validity of the contig was
      further strengthened by the results of chromosome nested fractionation with
      meganuclease I-SceI. An EcoRI restriction map of the contig enabled further
      verification and measurement of the total length of the contig, that was found to
      be approximately 700 kb in size. In addition to providing a base for the ongoing
      yeast genome sequencing project, the physical map can be used to map any sequence
      belonging to chromosome X.

PMID- 7803815
TI  - Characterization of two putative Listeria monocytogenes genes encoding
      polypeptides homologous to the sensor protein CheA and the response regulator
      CheY of chemotaxis.
AB  - The nucleotide sequence of a region located downstream of the Listeria
      monocytogenes flagellin gene, flaA, has been determined. DNA sequence analysis
      revealed the presence of two open reading frames with a potential to encode
      polypeptides of 13.1 and 68.7 kDa, respectively. The deduced polypeptides show a
      high degree of identity to the chemotactic proteins, CheY and CheA, respectively,
      from Bacillus subtilis and Escherichia coli. Moreover, significant features of
      CheY and CheA are conserved in the L. monocytogenes homologues. The high degree
      of conservation suggests that the polypeptides are involved in signal
      transduction controlling chemotaxis in L. monocytogenes and consequently the
      putative genes are named cheY and cheA. Northern blot and primer extension
      analysis suggested that cheY and cheA are transcribed as a bicistronic unit and
      that the transcription is thermoregulated.

PMID- 7803816
TI  - Isolation and characterization of a cDNA clone coding for the calcium-binding
      subunit of calcineurin from bovine brain: an identical amino acid sequence to the
      human protein.
AB  - A cDNA clone encoding the calcium-binding subunit of calcineurin, calcineurin B,
      was isolated from a bovine brain library by immunoscreening. The 841 bp cDNA has
      a 56 bp 5'-noncoding region, an open reading frame of 510 bp, and a 275 bp 3'
      noncoding sequence. The deduced amino acid sequence of bovine calcineurin B
      differs from the previously reported protein sequence (Aitken et al., 1984) by
      three residues. The sequence contained additional valine at the carboxyl terminus
      and substitutions of Met-11 and Ser-153 (the positions according to Aitken et
      al., 1984) by cysteine. The amino acid sequence of bovine calcineurin B was found
      to be identical to that of human calcineurin B sequence (Guerini et al., 1989).
      In fact, 97.1% homology was observed between the coding regions of human and
      bovine calcineurin B. In addition, a very high homology of 95.2% was observed for
      the 3'-noncoding region while the 5'-noncoding region showed 58.9% homology. The
      beta-galactosidase fusion protein, having the apparent molecular weight of 29
      kDa, was detected on Western blots by subunit B-specific monoclonal antibody
      (Matsui et al., 1985). Northern analysis revealed that there is a single
      calcineurin B transcript in bovine brain which is 2.3 kb in length. This is in
      agreement with the observation of only one immunologically detectable subunit B
      protein in bovine brain (Matsui et al., 1985).

PMID- 7803817
TI  - The 5' flanking region of the rat beta 3-adrenergic receptor gene: divergence
      with the human gene and implications for species-specific gene expression.
AB  - beta 3-adrenergic receptor mRNAs exhibit species-specific expression (human vs.
      rodent) in distinct anatomical regions and appear to be expressed abundantly
      within rodent adipose tissue, but only at low levels within corresponding human
      tissues. In order to determine the genetic basis of the differential expression
      of the rat and human beta 3-adrenergic receptor genes, we cloned and sequence the
      rat gene and compared the 5' flanking regions of the two genes to identify
      potential discriminators in transcriptional regulation. We have found that the
      rat and human beta 3-adrenergic receptor 5' flanking regions are only 67%
      similar, unlike the close sequence similarity observed between the coding blocks
      (> 90%) and also observed between species for the 5' flanking regions of other
      beta-adrenergic receptor subtype genes (> 90%). In addition, the rat beta 3
      adrenergic receptor gene lacks the four potential cAMP responsive elements
      identified within the 5' flanking region of the human receptor gene. The striking
      divergence in regulatory sequences between the rat and human beta 3-adrenergic
      receptor genes may potentially explain the differences in species-specific
      expression and tissue localization of the rat and human receptor mRNAs.

PMID- 7803818
TI  - Cloning and sequencing the streptolysin O genes of group C and group G
      streptococci.
AB  - On the basis of the known streptolysin O (SLO) genomic sequence of Streptococcus
      pyogenes group A, we identified the SLO genes in some strains of group C and
      group G streptococci by the polymerase chain reaction procedure (PCR). The entire
      open reading frame region of these genes was cloned and analyzed. Their
      nucleotide sequence data showed that the defined SLO genes in group C and group G
      are almost identical to that of group A.

PMID- 7803819
TI  - A 14.4 KDa acidic subunit of human RNA polymerase II with a putative leucine
      zipper.
AB  - The cDNA of a small subunit (hRPB14.4) of RNA polymerase II (or B) from HeLa
      cells has been cloned. A 127 residue peptide sequence (calculated molecular
      weight of 14,478; isoelectric point of 3.7) was deduced and compared to that of
      the homologous subunit of Saccharomyces cerevisiae polymerase (ABC23, encoded by
      the RPB6/RPO26 gene). About 50% of the total residues were found to be conserved
      between yeast and man, with the C-terminal two-third being the most conserved
      (72% identity). A putative leucine-zipper comprising four properly spaced leucine
      residues, but not preceded by a basic domain, was identified near the C-terminal
      end of both proteins.

PMID- 7803820
TI  - 16S ribosomal RNA gene sequence and phylogeny of toxic Microcystis sp.
      (cyanobacteria).
AB  - The toxigenic and bloom-forming cyanobacterial genus Microcystis contains several
      ill-defined species. The 16S rDNA for two strains of toxic M. aeruginosa were
      sequenced and compared to available cyanobacterial, bacterial, and chloroplast
      16S rRNA gene information. Phylogeny and the validity of a molecular taxonomy for
      the genus Microcystis is presented.

PMID- 7803821
TI  - Nucleotide sequence of mouse spermidine synthase cDNA.
AB  - The nucleotide sequence of mouse cDNA for spermidine synthase appeared to contain
      75 nucleotides of 5' untranslated region, an open reading frame of 909
      nucleotides and 297 nucleotides of 3' untranslated region. The open reading frame
      encoded a polypeptide of 302 amino acids, displaying 95% similarity to human and
      33% similarity to E. coli spermidine synthase. The 3' flanking region contained
      an unusual polyadenylation signal AATACA.

PMID- 7803822
TI  - Preventive ethics and alleviating care providers' stress.

PMID- 7803823
TI  - Preventive ethics: expanding the horizons of clinical ethics.

PMID- 7803824
TI  - Impairments and impediments in patients' decision making: reframing the
      competence question.

PMID- 7803825
TI  - Brain death in pregnant women.

PMID- 7803826
TI  - The Psychiatric Admission Index: deciding when to admit a patient.

PMID- 7803827
TI  - The effect on researchers of handling human fetal tissue.

PMID- 7803828
TI  - Case 1: rational suicide or involuntary commitment of a patient who is terminally
      ill.

PMID- 7803829
TI  - The case of Ms. A and her nurse-therapist.

PMID- 7803830
TI  - A model system works: looking deeper than suicide.

PMID- 7803831
TI  - On promoting rational treatment, not rational suicide.

PMID- 7803832
TI  - Case 2: decisions to refuse treatment by depressed, medically ill patients.

PMID- 7803833
TI  - Depression, suicide, and the right to refuse life-sustaining treatment.

PMID- 7803834
TI  - Incubators and organ donors.

PMID- 7803835
TI  - Have we lost our senses? Problems with maintaining brain-dead bodies carrying
      fetuses.

PMID- 7803836
TI  - Clinical management of brain death during pregnancy.

PMID- 7803837
TI  - An algorithm in a different world.

PMID- 7803838
TI  - Is admission to a psychiatric hospital an ethical alternative to home-based
      treatment?

PMID- 7803839
TI  - Cases and social reality: making the decision to admit.

PMID- 7803840
TI  - The psychological and moral consequences of participating in human fetal-tissue
      research.

PMID- 7803841
TI  - Prolonged grieving after abortion: a descriptive study.

PMID- 7803842
TI  - Questionable competency of a surrogate decision maker under a durable power of
      attorney.

PMID- 7803843
TI  - Brain death and slippery slopes.

PMID- 7803844
TI  - Abnormal development of embryonic and extraembryonic cell lineages in
      parthenogenetic mouse embryos.
AB  - Parthenogetically activated, diploid mouse oocytes can develop to midgestation
      stages in utero. However, even these advanced parthenogenones appear to die
      because of much reduced trophoblast and yolk sac development. Previous studies
      have compared the general features of parthenogenetic and androgenetic
      development and determined the fate of uniparental cells in chimeras with normal
      embryos. These studies led to the concept of genomic imprinting as the cause for
      developmental failure when either the maternal or the paternal genome is
      duplicated, with the corresponding deficiency of the other. Genomic imprinting
      appears to arise during gametogenesis and to act through dosage effects in a set
      of imprinted genes, whose expression depends on their parental origin. In this
      study we undertook a more detailed morphological analysis of parthenogenetic
      development in the mouse and established a classification system to quantify the
      developmental extent of parthenogenones. We found that the failure of
      parthenogenones occurred at different times during early postimplantation
      development, generating a spectrum of concepti which had developed to different
      extents, with only a small fraction of the embryos reaching advanced somite
      stages. In all parthenogenones differentiation and proliferation of the
      trophectoderm and primitive endoderm lineages (both extraembryonic) was abnormal,
      and in all, even the best-developed parthenogenones, we observed similar
      deficiencies in the embryonic lineages, especially the mesoderm. Common to all
      abnormally developed lineages was that the proportion of undifferentiated
      precursor cells was much reduced, while their differentiated descendants were
      relatively abundant. We propose, therefore, that the failure of parthenogenones
      to develop to term is due to abnormal regulation of differentiation and
      proliferation in both embryonic and extraembryonic lineages. In this hypothesis,
      the apparent tissue specific defects observed in parthenogenones arise as a
      consequence of the functional importance of certain tissues (like the
      trophoblast) early in development. The spectrum of parthenogenones thus appears
      to reflect critical events in early development, whose regulation are affected by
      genomic imprinting.

PMID- 7803845
TI  - Time-lapse total internal reflection fluorescence video of acetylcholine receptor
      cluster formation on myotubes.
AB  - To study when and where acetylcholine receptor (AChR) clusters appear on
      developing rat myotubes in primary culture, we have made time-lapse movies of
      total internal reflection fluorescence (TIRF) overlaid with schlieren transmitted
      light images. The receptors, including the ones newly incorporated into the
      membrane, were labeled with rhodamine alpha-bungarotoxin (R-BT) continuously
      present in the medium. Since TIRF illuminates only cell-substrate contact regions
      where almost all of the AChR clusters are located, background fluorescence from
      fluorophores either in the bulk solution or inside the cells can be suppressed.
      Also, because TIRF minimizes the exposure of the cell interior to light, the
      healthy survival of the culture during imaging procedures is much enhanced
      relative to standard epi- (or trans-) illumination. During the experiment, cells
      were kept alive on the microscope stage at 37 degrees C in an atmosphere of 10%
      CO2. Two digital images were recorded by a CCD camera every 20 min: the schlieren
      image of the cells and the TIRF image of the clusters. After background
      subtraction, the cluster image was displayed in pseudocolors, overlaid onto the
      cell images, and recorded as 3 frames on a videotape. The final movies are thus
      able to summarize a week-long experiment in less than a minute. These movies and
      images show that clusters form often shortly after the myoblast fusion but
      sometimes much later, and the formation takes place very rapidly (a few hours).
      The clusters have an average lifetime of around a day, much shorter than the
      lifetime of a typical myotube. The brightest and largest clusters tend to be the
      longest-lived. The cluster formation seems to be associated with the contacts of
      myotubes at the glass substrate, but not with cell-cell contacts or myoblast
      fusion into myotubes. New AChR continuously appear in preexisting clusters: after
      photobleaching, the fluorescence of some clusters recovers within an hour.

PMID- 7803846
TI  - Enhancement of skeletal muscle regeneration.
AB  - We have studied the effect of adding extra satellite cells or soluble factors
      from crushed muscle on regeneration of minced fragments from rat tibialis muscle.
      The muscle mince was wrapped in an artificial epimysium to prevent adhesions and
      cell immigration from adjacent muscles. Regeneration was quantitatively assessed
      by electrophoretic determination of the muscle-specific form of creatine kinase.
      Control minces exhibited three periods of change in creatine kinase activity
      during a 7-week regeneration period. Activity fell rapidly during the first week,
      then rose gradually from 1-3 weeks and increased more rapidly from 3-7 weeks. To
      augment the original complement of myogenic cells, satellite cells were isolated
      from the contralateral muscle, purified by density gradient centrifugation, and
      expanded in culture for 3 days before adding to the muscle mince. The added cells
      resulted in a 3-fold enhancement of creatine kinase activity throughout the
      regeneration period. Soluble muscle extract incorporated into a collagen matrix
      also stimulated regeneration when added to muscle mince. The extract accelerated
      the rate of creatine kinase increase during the 1-3 week period beyond that
      observed in the control or cell augmented mince, suggesting that factors in the
      extract may facilitate revascularization or reinnervation. The specific activity
      of creatine kinase was increased in regenerates augmented with both cells and
      extract, indicating that the effects enhance primarily myogenic processes.

PMID- 7803847
TI  - In vitro analysis of the spatial organization of chondrogenic regions of avian
      mandibular mesenchyme.
AB  - The mechanism(s) which control patterning in the face remain elusive, due in
      large part to the absence of morphologically identifiable controlling regions
      such as the AER of the limb bud. In order to identify the controlling region(s)
      and timing of patterning in the face, an investigation was launched to determine
      the spatial organization of tissues within this region, beginning with the
      chondrogenic zones of the avian (chick and quail) mandible. The mandibles from HH
      stage 23/24 chick and equivalent stage quail embryos were initially bisected in
      three planes giving rostral or caudal, proximal or distal, and medial or lateral
      halves. The mesenchyme from these various regions was isolated, plated out in
      high density micromass cultures, and grown for 4 days. Additionally, further
      cultures were grown, consisting of mandibular mesenchyme subdivided into quarters
      along the long axis of the mandible (e.g., rostro-proximal quarter) as well as
      the bisecting of medial or lateral halves (e.g., medial-rostral quarter). Nodule
      number and area were determined by morphometric analysis for each culture as well
      as whole mandible controls. The demarcation between chondrogenic and non
      chondrogenic regions was dramatic. Of the bisected halves, proximal and lateral
      were the most chondrogenic with the lateral subdivision displaying much more
      cartilage than whole mandible. The nodules of the lateral cultures fused into a
      sheet of cartilage. In contrast mesenchyme from the medial half was virtually non
      chondrogenic. When ranked by the amount of chondrogenesis, the order was, lateral
      > proximal = whole = core > distal > caudal > rostral > periphery >> medial.
      Interestingly, when subdivided further an altered pattern appeared.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7803848
TI  - Immunohistochemical studies indicate multiple enteroendocrine cell
      differentiation pathways in the mouse proximal small intestine.
AB  - The enteroendocrine cell system of the mammalian gastrointestinal tract is
      comprised of at least 16 different subpopulations. Each subpopulation shows a
      characteristic distribution along both the crypt-villus and cephalo-caudal axes.
      In both the small intestine and colon of adult mice, multilabel
      immunohistochemistry has demonstrated that two or more neuroendocrine products
      can be coexpressed in various combinations in single cells along the crypt-villus
      axis, suggesting that enteroendocrine phenotypes may be actively regulated. Using
      bromodeoxyuridine (BrdU) incorporation and multilabel immunohistochemistry, we
      have previously demonstrated an enteroendocrine cell differentiation pathway
      consisting of two subpopulations of cells in the mouse proximal small intestine-
      one involving the sequential expression of substance P, serotonin, and secretin
      in cells migrating out of the crypts into the villi, and a second involving the
      expression of substance P and serotonin in cells which remain in the crypts. In
      this report, we use double label immunohistochemistry and BrdU incorporation to
      define the temporal and spatial interrelationships between gastrin,
      cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), and gastric inhibitory
      peptide (GIP) immunoreactive cells in the mouse proximal small intestine. The
      expression of these products was compared with that of substance P, serotonin,
      and secretin. Minimal overlap of expression was found in cells immunoreactive for
      substance P or serotonin with gastrin, CCK, GLP-1, or GIP; however, secretin was
      found colocalized in villus-associated gastrin, CCK, and GLP-1 containing
      cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7803849
TI  - Differential expression of laminin isoforms and alpha 6-beta 4 integrin subunits
      in the developing human and mouse intestine.
AB  - The intestinal tissue is characterized by important morphogenetic movements
      during development as well as by a continuous dynamic crypt to villus epithelial
      cell migration leading to differentiation of specialized cells. In this study, we
      have examined the spatio-temporal distribution of laminin A and M chains as well
      as of alpha 6 and beta 4 integrin subunits in adult and developing human and
      mouse intestine by indirect immunofluorescence. Selective expression of the
      constituent polypeptides of laminin isoforms (A and M chains) was demonstrated.
      In the mature human intestine, A and M chains were found to be complementary, the
      M chain being restricted to the base of crypts and the A chain lining the villus
      basement membrane. In the developing human intestine, M chain expression was
      delayed as compared to that of A chain; as soon as the M chain was visualized, it
      exhibited the typical localization in the crypt basement membrane. A somewhat
      different situation was found in the adult mouse intestine, since both M and A
      chains were found in the crypts. During mouse intestinal development the delayed
      expression of the M chain as compared to that of the A chain was also obvious.
      The absence of M chain expression in mutant dy mouse did not impair intestinal
      morphogenesis nor cell differentiation. The expression of alpha 6 and beta 4
      subunits was not coordinated. In both species the alpha 6 expression preceded
      that of beta 4. Furthermore, while beta 4 staining in adult mouse intestine was
      detected at the basal surface of all cells lining the crypt-villus, that of alpha
      6 was mainly confined to the crypt cell compartment. An overall similarity of
      location between alpha 6 integrin subunit and laminin A chain at the
      epithelial/stromal interface was noted. These data indicate that the spatial and
      temporal distribution of laminin variants in the developing intestine may be
      characteristic for each species and that interactions of laminin variants with
      particular receptors may be important for induction and/or maintenance of
      differentiated cells.

PMID- 7803850
TI  - Caenorhabditis elegans sqt-3 mutants have mutations in the col-1 collagen gene.
AB  - sqt-3 mutants of Caenorhabditis elegans form dumpy larvae and adults and display
      allele-specific defects in locomotion, fertility, and viability. We have
      determined that the sqt-3 locus encodes COL-1 collagen. We physically mapped the
      col-1 gene to a cosmid on chromosome V whose position is consistent with the
      location of the sqt-3 gene. We also observed morphological defects in sqt-3
      mutants at stages that correlate with the mRNA expression patterns of col-1.
      Sequence analysis of the col-1 gene in the three temperature-sensitive mutants
      revealed that each allele of sqt-3 has a unique missense mutation causing
      arginine or glutamic acid to replace glycine in a Gly-X-Y triple helical domain.
      These glycine substitutions may result in longer non-collagenous domains, which
      may decrease the thermal stability or impart additional flexibility to mutant
      trimers. In addition, we describe four corrections to the published sequence of
      col-1, including one fifteen nucleotide addition that completes a conserved
      domain in the amino terminal coding region.

PMID- 7803851
TI  - Assembly of alcohol oxidase in peroxisomes of the yeast Hansenula polymorpha
      requires the cofactor flavin adenine dinucleotide.
AB  - The peroxisomal flavoprotein alcohol oxidase (AO) is an octamer (600 kDa)
      consisting of eight identical subunits, each of which contains one flavin adenine
      dinucleotide molecule as a cofactor. Studies on a riboflavin (Rf) auxotrophic
      mutant of the yeast Hansenula polymorpha revealed that limitation of the cofactor
      led to drastic effects on AO import and assembly as well as peroxisome
      proliferation. Compared to wild-type control cells Rf-limitation led to 1)
      reduced levels of AO protein, 2) reduced levels of correctly assembled and
      activated AO inside peroxisomes, 3) a partial inhibition of peroxisomal protein
      import, leading to the accumulation of precursors of matrix proteins in the
      cytosol, and 4) a significant increase in peroxisome number. We argue that the
      inhibition of import may result from the saturation of a peroxisomal molecular
      chaperone under conditions that normal assembly of a major matrix protein inside
      the target organelle is prevented.

PMID- 7803852
TI  - Physical mapping of origins of replication in the fission yeast
      Schizosaccharomyces pombe.
AB  - We isolated four fragments from the Schizosaccharomyces pombe genome that mediate
      autonomous replication. A two-dimensional gel analysis revealed that in each case
      initiation could be mapped to within the S. pombe sequences. In three of the
      fragments, initiation could be mapped to one discrete location. In the fourth
      fragment, subcloning and two-dimensional gel analysis suggested that two discrete
      origins of replication were located within 3 kb of each other. When in proximity,
      usually only one of these origins fired, suggesting origin interference. Two
      dimensional gel analysis of the four origin fragments at their genomic locations
      demonstrated that each is used in the chromosomes, but in only a subset of cells
      or cell divisions. The S. pombe genome appears to contain many discrete origins,
      not all of which fire in any given cell and some of which are closely spaced. Not
      I/Sfi I mapping of the five origins from this and a previous study indicates that
      they are randomly distributed throughout the genome and appear to be
      representative of chromosomal origins of replication in this organism. We compare
      the features of S. pombe replication origins with those of S. cerevisiae and
      animal cells.

PMID- 7803853
TI  - Alternative splicing in fibroblast growth factor receptor 2 is associated with
      induced epithelial-mesenchymal transition in rat bladder carcinoma cells.
AB  - We described previously that acidic fibroblast growth factor (aFGF), but not
      basic fibroblast growth factor (bFGF), can induce the rat carcinoma cell line NBT
      II to undergo a rapid and reversible transition from epithelial to mesenchymal
      phenotype (EMT). We now find that NBT-II EMT is stimulated by keratinocyte growth
      factor (KGF) in cells grown at low density. Accordingly, a high-affinity receptor
      showing 98% homology to mouse FGF receptor 2b/KGF receptor was cloned and
      sequenced from NBT-II cells. Northern analysis indicated that mRNA for FGF
      receptor 2b/KGF receptor was drastically down-regulated within 1 wk in aFGF
      induced mesenchymal NBT-II cells. This decrease coincided with an up-regulation
      of FGF receptor 2c/Bek, a KGF-insensitive, alternatively spliced form of FGF
      receptor 2b/KGF receptor. Functional studies confirmed that KGF could not
      maintain EMT induction on mesenchymal NBT-II cells. FGF receptor 1 and FGF
      receptor 2c/Bek could also support EMT induction when transfected into NBT-II
      cells in response to aFGF or bFGF. Such transfected cells could bind bFGF as well
      as aFGF. Therefore, EMT can be induced through different FGF receptors, but EMT
      may also regulate FGF receptor expression itself.

PMID- 7803854
TI  - Respective roles of neurofilaments, microtubules, MAP1B, and tau in neurite
      outgrowth and stabilization.
AB  - The respective roles of neurofilaments (NFs), microtubules (MTs), and the
      microtubule-associated proteins (MAPs) MAP 1B and tau on neurite outgrowth and
      stabilization were probed by the intracellular delivery of specific antisera into
      transiently permeabilized NB2a/d1 cells during treatment with dbcAMP.
      Intracellular delivery of antisera specific for the low (NF-L), middle (NF-M), or
      extensively phosphorylated high (NF-H) molecular weight subunits did not prevent
      initial neurite elaboration, nor did it induce retraction of existing neurites
      elaborated by cells that had been previously treated for 1 d with dbcAMP. By
      contrast, intracellular delivery of antisera directed against tubulin reduced the
      percentage of cells with neurites at both these time points. Intracellular
      delivery of anti-NF-L and anti-NF-M antisera did not induce retraction in cells
      treated with dbcAMP for 3 d. However, intracellular delivery of antisera directed
      against extensively phosphorylated NF-H, MAP1B, tau, or tubulin induced similar
      levels of neurite retraction at this time. Intracellular delivery of monoclonal
      antibodies (RT97 or SMI-31) directed against phosphorylated NF-H induced neurite
      retraction in cell treated with dbcAMP for 3 d; a monoclonal antibody (SMI-32)
      directed against nonphosphorylated NF-H did not induce neurite retraction at this
      time. By contrast, none of the above antisera induced retraction of neurites in
      cells treated with dbcAMP for 7 d. Neurites develop resistance to retraction by
      colchicine, first detectable in some neurites after 3 d and in the majority of
      neurites after 7 d of dbcAMP treatment. We therefore examined whether or not
      colchicine resistance was compromised by intracellular delivery of the above
      antisera. Colchicine treatment resulted in rapid neurite retraction after
      intracellular delivery of antisera directed against extensively phosphorylated NF
      H, MAP1B, or tau into cells that had previously been treated with dbcAMP for 7 d.
      By contrast, colchicine resistance was not compromised by the intracellular
      delivery of antisera directed against NF-L, NF-M, or tubulin. These findings
      support previous studies indicating that MT polymerization mediates certain
      aspects of axonal neurite outgrowth and suggest that NFs do not directly
      participate in these events. These findings further suggest that NFs function in
      stabilization of the axonal cytoskeleton, apparently by interactions among NFs
      and MTs that are mediated by NF-H and MAPs.

PMID- 7803855
TI  - Budding and fission yeast casein kinase I isoforms have dual-specificity protein
      kinase activity.
AB  - We have examined the activity and substrate specificity of the Saccharomyces
      cerevisiae Hrr25p and the Schizosaccharomyces pombe Hhp1, Hhp2, and Cki1 protein
      kinase isoforms. These four gene products are isotypes of casein kinase I (CKI),
      and the sequence of these protein kinases predicts that they are protein
      serine/threonine kinases. However, each of these four protein kinases, when
      expressed in Escherichia coli in an active form, was recognized by anti
      phosphotyrosine antibodies. Phosphoamino acid analysis of 32P-labeled proteins
      showed phosphorylation on serine, threonine, and tyrosine residues. The E. coli
      produced forms of Hhp1, Hhp2, and Cki1 were autophosphorylated on tyrosine, and
      both Hhp1 and Hhp2 were capable of phosphorylating the tyrosine-protein kinase
      synthetic peptide substrate polymer poly-E4Y1. Immune complex protein kinases
      assays from S. pombe cells showed that Hhp1-containing precipitates were
      associated with a protein-tyrosine kinase activity, and the Hhp1 present in these
      immunoprecipitates was phosphorylated on tyrosine residues. Although
      dephosphorylation of Hhp1 and Hhp2 by Ser/Thr phosphatase had little effect on
      the specific activity, tyrosine dephosphorylation of Hhp1 and Hhp2 caused a 1.8
      to 3.1-fold increase in the Km for poly-E4Y1 and casein. These data demonstrate
      that four different CKI isoforms from two different yeasts are capable of protein
      tyrosine kinase activity and encode dual-specificity protein kinases.

PMID- 7803856
TI  - Signal sequence recognition and targeting of ribosomes to the endoplasmic
      reticulum by the signal recognition particle do not require GTP.
AB  - The identification of GTP-binding sites in the 54-kDa subunit of the signal
      recognition particle (SRP) and in both the alpha and beta subunits of the SRP
      receptor has complicated the task of defining the step in the protein
      translocation reaction that is controlled by the GTP-binding site in the SRP.
      Ribonucleotide binding assays show that the purified SRP can bind GDP or GTP.
      However, crosslinking experiments show that SRP54 can recognize the signal
      sequence of a nascent polypeptide in the absence of GTP. Targeting of SRP
      ribosome-nascent polypeptide complexes, formed in the absence of GTP, to
      microsomal membranes likewise proceeds normally. To separate the GTPase cycles of
      SRP54 and the alpha subunit of the SRP receptor (SR alpha), we employed an SR
      alpha mutant that displays a markedly reduced affinity for GTP. We observed that
      the dissociation of SRP54 from the signal sequence and the insertion of the
      nascent polypeptide into the translocation site could only occur when GTP binding
      to SR alpha was permitted. These data suggest that the GTP binding and hydrolysis
      cycles of both SRP54 and SR alpha are initiated upon formation of the SRP-SRP
      receptor complex.

PMID- 7803857
TI  - Mitochondrial morphological and functional defects in yeast caused by yme1 are
      suppressed by mutation of a 26S protease subunit homologue.
AB  - The absence of functional Yme1p, a putative ATP and zinc-dependent protease
      localized to mitochondria of yeast, results in abnormal mitochondrial function
      and morphology. Yeast lacking Yme1p lose DNA from mitochondria at an accelerated
      rate, fail to grow on nonfermentable carbon sources at 37 degrees C, and have
      severely deficient growth if mitochondrial DNA suffers large deletions or is
      completely lost. In place of the normal reticulated mitochondrial network,
      strains lacking Yme1p have punctate mitochondria with some grossly swollen
      compartments. The growth phenotypes and morphological alterations evident in
      these mutant yeast can be compensated by a mutation in YNT1, an essential gene in
      yeast. The sequence of the YNT1 gene product indicates that it is one of a number
      of related regulatory subunits of the 26S protease. This proteolytic activity is
      necessary for progression through the cell cycle and has been implicated in the
      regulation of transcription. Ynt1p is more distantly related to Yme1p.

PMID- 7803860
TI  - The role of the role model.

PMID- 7803858
TI  - Expression of mammalian protein kinase C in Schizosaccharomyces pombe: isotype
      specific induction of growth arrest, vesicle formation, and endocytosis.
AB  - Mammalian protein kinase C (PKC) isotypes elicit a number of effects on
      expression in Schizosaccharomyces pombe. A small decrease in growth rate results
      from PKC-gamma expression, and treatment of these cells with phorbol esters leads
      to marked growth inhibition and vesicle formation. PKC-delta and -eta expression
      causes growth inhibition and vesiculation, and the magnitude of both of these
      effects is increased by phorbol esters. In contrast, PKC-epsilon expression
      produces growth inhibition but no vesicle accumulation, and this effect is not
      responsive to phorbol ester. Finally, PKC-zeta has no observable effect. Thus,
      isotype-specific biological effects are observed. The accumulation of vesicles
      correlates with phorbol ester-dependent growth inhibition and occurs only with
      expression of those isotypes that down-regulate in response to phorbol esters in
      these cells. Antibodies against mammalian clathrin light chain 1a identified
      clathrin-coated vesicles and up-regulation of clathrin expression in those cells
      where vesicles accumulate; the increased vesicular traffic includes an element of
      endocytosis. Thus expression of specific mammalian PKC isotypes up-regulates
      endocytosis in S. pombe, providing a likely explanation for PKC-mediated receptor
      internalization in higher eukaryotes.

PMID- 7803861
TI  - Sir William Osler: a second opinion.

PMID- 7803862
TI  - Public health crisis looms unless liability laws change.

PMID- 7803859
TI  - Expression and activity of p40MO15, the catalytic subunit of cdk-activating
      kinase, during Xenopus oogenesis and embryogenesis.
AB  - Threonine 161 phosphorylation of p34cdc2 and its equivalent threonine 160 in
      p33cdk2 by cdk-activating kinase (CAK) is essential for the activation of these
      cyclin-dependent kinases. We have studied the expression and associated kinase
      activity of p40MO15, the catalytic subunit of CAK, during Xenopus oogenesis,
      meiotic maturation, and early development to understand in more detail how cdk
      kinases are regulated during these events. We find that p40MO15 is a stable
      protein with a half-life > 16 h that is accumulated during oogenesis. p40MO15
      protein and its associated CAK activity are localized predominantly to the
      germinal vesicle; however, a small but significant proportion is found in the
      cytoplasm. The amount of p40MO15 detected in stage VI oocytes remains unchanged
      through meiotic maturation, fertilization, and early embryogenesis.
      Significantly, p40MO15 was found to be constitutively active during oogenesis,
      meiotic maturation, and the rapid mitotic cycles of early development. This
      suggests that regulation of p34cdc2 and p33cdk2 activity during cell cycle
      progression does not involve changes in the level or activity of p40MO15/CAK.

PMID- 7803863
TI  - The deadly nightshades.

PMID- 7803864
TI  - The Physician's Health Committee of the Rhode Island Medical Society.

PMID- 7803865
TI  - Treatment outcome studies on physician impairment: a review of the literature.

PMID- 7803866
TI  - Psychiatric issues in physician impairment.

PMID- 7803867
TI  - On seduction and exploitation: a medical model approach.

PMID- 7803868
TI  - The impaired physician and the role of the Board of Medical Licensure and
      Discipline.

PMID- 7803869
TI  - Guidelines for screening mammography: the controversy.

PMID- 7803870
TI  - Diagnosing breast cancer at earlier stages of disease.

PMID- 7803871
TI  - Clinical experience with ketorolac in children.
AB  - OBJECTIVE: To describe the use of parenteral ketorolac in a large population of
      children, focusing on dosing patterns, efficacy, and safety. DESIGN:
      Observational, prospective study conducted over a four-month period. SETTING: A
      122-bed children's medical center located within an academic medical center
      hospital. PARTICIPANTS: Children receiving ketorolac during their
      hospitalization. MAIN OUTCOME PARAMETERS: Indications for treatment, dose, dosing
      interval, use of a loading dose, length of therapy, efficacy (subjective response
      and use of concomitant therapy), and adverse effects (bleeding, gastrointestinal
      ulceration or vomiting, and renal dysfunction). RESULTS: Of 112 children
      evaluated, 110 received ketorolac for analgesia, and 2 were given ketorolac as an
      antipyretic. The children ranged in age from 6 months to 19 years. Doses of 0.5
      mg/kg q6h were used for most children (range 0.17-1.0). The average length of
      therapy was 3.4 days (range 1-12). The most frequent reason for discontinuing
      ketorolac therapy was a change to oral therapy. Therapy was discontinued because
      of a lack of efficacy in only 2 children. Adverse reactions were unusual, with
      only 2 patients having bleeding potentially associated with ketorolac use.
      CONCLUSIONS: Ketorolac appears to be a safe and effective therapy for children
      when given in appropriate doses for a limited duration.

PMID- 7803872
TI  - Stability and activity of intravenous immunoglobulin with neonatal dextrose and
      total parenteral nutrient solutions.
AB  - OBJECTIVE: To determine in vitro the compatibility of reconstituted intravenous
      immunoglobulin (IVIG) (Gammagard, Baxter-Hyland) with five different neonatal and
      pediatric intravenous solutions in Viaflex polyvinyl chloride bags. DESIGN: In
      vitro compatibility study. INTERVENTIONS: Samples were taken at time = 0, 10, 30,
      60, 90, and 120 minutes and at 4, 8, 12, and 24 hours and assayed for total
      immunoglobulin G content and antibodies to hepatitis B surface antigen. Type III
      group B Streptococcus (GBS) and opsonic activity for type III GBS were analyzed
      at time = 0, 60, and 120 minutes and 12 and 24 hours. All results were compared
      with those from pure IVIG. RESULTS: Our results demonstrate that mixing IVIG with
      intravenous solutions commonly used in the care of premature infants (dextrose 5%
      in water [D5W], D15W, D5W/NaCl 0.225%, and total parenteral nutrition [TPN]) does
      not significantly alter total immunoglobulin G concentrations or concentration of
      antibodies to hepatitis B surface antigen or type III GBS. As well, the in vitro
      functional activity for type III GBS of the IVIG, when mixed with these solutions
      for up to 24 hours, remained intact. An apparent decrease in bactericidal killing
      was seen with the IVIG/central TPN mixture. This apparent decrease was found to
      be an artifact of the high concentration of glucose (20 percent) in the solution.
      CONCLUSIONS: We propose that Gammagard may be mixed with these solutions through
      Y-site connections without loss of antibody content or functional activity of the
      IVIG.

PMID- 7803873
TI  - Stability of diluted dexamethasone sodium phosphate injection at two
      temperatures.
AB  - OBJECTIVE: Premature neonates with bronchopulmonary dysplasia frequently are
      treated with intravenous dexamethasone for their chronic lung disease. The
      injection volumes of the commercially available products often are too small to
      measure accurately. The objective of this study was to evaluate the stability
      over 28 days of dexamethasone sodium phosphate injection 4 mg/mL diluted with
      bacteriostatic NaCl 0.9% to 1 mg/mL. DESIGN: Ten vials of dexamethasone 1 mg/mL
      were prepared from dexamethasone sodium phosphate injection, USP 4 mg/mL and
      bacteriostatic NaCl 0.9% injection. Five vials were stored at 4 degrees C and
      five at 22 degrees C. Dexamethasone was measured on days 0, 1, 3, 7, 14, 21, and
      28 by an accurate, reproducible, and stability-indicating HPLC method. Samples
      were also inspected visually for precipitation or discoloration on each study
      day. RESULTS: The samples retained at least 97.7 percent of the original
      concentration of dexamethasone sodium phosphate when stored at either 4 or 22
      degrees C for 28 days. No discoloration or precipitation was observed.
      CONCLUSIONS: Dexamethasone sodium phosphate injection 1 mg/mL in bacteriostatic
      NaCl 0.9% was stable for 28 days at 4 and 22 degrees C.

PMID- 7803875
TI  - Pancreatitis during intravenous pentamidine therapy in an AIDS patient with prior
      exposure to didanosine.
AB  - OBJECTIVE: To report a case of an HIV-positive man who received sequential
      didanosine and pentamidine treatment and subsequently developed acute clinical
      pancreatitis. CASE SUMMARY: In June 1992 didanosine 200 mg po bid was initiated
      in a 30-year-old man with AIDS. After a 22-week course of didanosine, the patient
      was hospitalized and didanosine was discontinued on day 4. The patient then
      received 8 days of treatment for a presumed Pneumocystis carinii pneumonia (PCP)
      with pentamidine 4 mg/kg/d iv. As the patient responded clinically to therapy, he
      was discharged home to complete a 21-day course of pentamidine. On day 14 of
      therapy, the patient experienced nausea, vomiting, diarrhea, fatigue, and was
      hypotensive. The dosage of pentamidine was reduced by 50 percent. After receiving
      18 doses of pentamidine, treatment was discontinued, as symptoms had worsened and
      serum amylase and lipase concentrations were elevated. The patient was
      hospitalized and the diagnosis of acute clinical pancreatitis was made. After a
      21-day hospitalization, the patient was discharged home in fair condition on
      hyperalimentation. DISCUSSION: Potential causes of pancreatitis, including
      opportunistic infections, neoplasms, and drugs, are discussed. The most probable
      factors associated with pancreatitis in our patient are didanosine and
      pentamidine therapy. CONCLUSIONS: As our patient developed pancreatitis following
      sequential administration of didanosine and pentamidine, it would be prudent to
      monitor for signs and symptoms of pancreatitis in similar cases. In addition,
      didanosine should be discontinued during and for one week following treatment of
      PCP when pentamidine is used.

PMID- 7803874
TI  - Omnibus Budget Reconciliation Act of 1990 and voluntarism: logistic regression
      analysis of pharmacist responsibility.
AB  - OBJECTIVE: To examine the relationship between pharmacists' willingness to assume
      further professional responsibilities, as measured by attitudes to the Omnibus
      Budget Reconciliation Act of 1990 (OBRA '90) requirements, and their attitudes
      toward voluntarism as their responsibility to society and their level of interest
      in their jobs. DESIGN: A survey was distributed to a convenience sample of 443
      pharmacists who were asked to indicate their responses on a number of items.
      SETTING: Surveys were distributed to participants in an annual pharmacy
      continuing education program. PARTICIPANTS: The response rate was 65 percent with
      completed surveys from 290 Florida pharmacists who were typically male (73
      percent) and practicing in the community setting (39 percent) for over 25 years
      (33 percent). MAIN OUTCOMES: Questions were aimed at gathering the following
      information: (1) demographics; (2) attitudes concerning the benefits of the three
      OBRA '90 requirements: patient counseling, prospective drug-use review (DUR), and
      information recording; (3) attitudes toward voluntarism; and (4) job interest.
      RESULTS: Pharmacists tended to agree that all three of the OBRA '90 mandates will
      be beneficial. Fifty-six percent favored the prospective DUR requirements, while
      68 percent favored the patient counseling requirements and 66 percent favored the
      information-recording requirements. Logistic regression analysis showed that unit
      increases in scaled responses, indicating more favorable attitudes toward
      believing that voluntarism was one's responsibility, increased the odds of
      favoring counseling by 38.7 percent and information recording by 32.4 percent. A
      similar directional relationship was found for the DUR requirement. Job interest
      did not add to the predictive ability of the variables already in the models.
      CONCLUSIONS: This study suggests a possible association between pharmacists'
      attitudes toward social responsibility and their acceptance of expanded
      professional responsibility.

PMID- 7803876
TI  - Anaphylactoid reactions associated with ondansetron.
AB  - OBJECTIVE: To describe two patients with anaphylactoid-type reactions to
      ondansetron. CASE SUMMARY: A 41-year-old man with grade III leiomyosarcoma of the
      right tibia was admitted to the hospital for his second dose of first-cycle
      neoadjuvant intraaterial cisplatin 60 mg/m2 therapy. He experienced an
      anaphylactoid reaction following intravenous ondansetron infusion that was
      confirmed on rechallenge. In a second case, premedication with intravenous
      ondansetron resulted in an anaphylactoid reaction in a 44-year-old woman with
      stage III ovarian cancer receiving her ninth course of cyclophosphamide and
      carboplatin. Both patients had received ondansetron previously with no adverse
      effects. DISCUSSION: Peer-reviewed journal articles and reports, obtained through
      a MEDLINE search, were reviewed. Information on the individual cases was obtained
      from the patients' medical records. Preservative changes in ondansetron infusion
      were examined as possible causes of the anaphylactoid reactions in our patients,
      but no conclusive data linking them were found. CONCLUSIONS: The efficacy and
      safety of ondansetron has led to the widespread use of this medication in the
      treatment of nausea and vomiting caused by cancer chemotherapy and radiation
      therapy. Practitioners should be made aware that acute severe anaphylactoid
      reactions could occur in patients who have previously received ondansetron with
      no adverse effects.

PMID- 7803877
TI  - Flecainide distribution, transplacental passage, and accumulation in the amniotic
      fluid during the third trimester of pregnancy.
AB  - OBJECTIVE: To study the disposition of flecainide acetate and its transplacental
      passage (both into the fetus and in the amniotic fluid) during the third
      trimester of pregnancy. DATA SOURCES: Reference articles and books are identified
      in the text. A literature review is presented. CASE SUMMARY: Flecainide
      distribution, transplacental passage, and accumulation into the amniotic fluid
      were studied in a patient at term presenting with a fetal supraventricular
      tachycardia diagnosed at 33 4/7 weeks of gestation. The fetal tachycardia was
      accompanied by cardiac failure with placental anasarca and hydramnios. Flecainide
      100 mg po bid was prescribed initially; by the time of delivery, the dosage had
      been decreased to 50 mg bid. At delivery day (39 5/7 weeks), the pharmacokinetics
      of total flecainide were studied at plateau. DATA SYNTHESIS: The concentrations
      of flecainide at birth in fetal and maternal blood and in amniotic fluid were
      235.4, 241.2, and 6426.5 micrograms/L, respectively. Calculation of a
      fetomaternal blood accumulation ratio of 0.97 showed that, at this gestational
      age, flecainide penetrates the placental membrane easily without accumulation in
      fetal blood. In contrast, the concentration of flecainide in amniotic fluid was
      approximately 27-fold that measured in maternal peripheral blood. Our results
      suggest the following: (1) close to term, the metabolic clearance (fetal hepatic
      clearance) of flecainide offers a high yield and its excretion by the fetal
      kidney is efficient; (2) given that amniotic fluid is constantly swallowed, it
      seems that, in contrast to what is seen in adults (relative oral bioavailability
      > or = 95 percent), the oral bioavailability of flecainide is possibly low in the
      fetus at term or close to term; under such circumstances, the drug would
      accumulate passively within the gestational sac; and (3) an alternative
      explanation is that the concentration in the fetus is, in part, the result of
      both transplacental crossing of the drug and reabsorption orally from the
      amniotic fluid. CONCLUSIONS: The regular therapeutic monitoring of flecainide is
      necessary and sufficient in the mother as the concentrations found appear to
      accurately reflect the degree of fetal accumulation. Because previous studies in
      infants and children have indicated few toxic adverse effects attributed to
      flecainide, it appears that the risk to a sucking infant of ingesting toxic
      amounts of flecainide in human breast milk is very low. Finally, the child of the
      patient described here has normal initial growth and development at the present
      time. The transplacental penetration of a drug can be considered, according to
      gestational age and the disorder being treated, as being of no consequence,
      dangerous, or desirable. Flecainide appears to fall into this last category.

PMID- 7803878
TI  - Neurologic sequelae associated with foscarnet therapy.
AB  - OBJECTIVE: To report three cases of possible foscarnet-induced neurologic
      sequelae. CASE SUMMARY: We report two cases of seizures and one case of hand
      cramping and finger paresthesia after starting foscarnet therapy with no evidence
      of predisposing risk factors, such as serum laboratory abnormalities, renal
      dysfunction, or known central nervous system (CNS) involvement. All three
      patients had stable laboratory values during therapy and when the neurologic
      adverse effects occurred. All patients were receiving appropriate dosages of
      foscarnet. DISCUSSION: The incidence of seizures in AIDS patients was reviewed. A
      history of CNS lesions, infections, and/or AIDS per se may increase the risk of a
      neurologic adverse effect while receiving foscarnet therapy. Acute ionized
      hypocalcemia may cause these neurologic adverse effects. Ionized hypocalcemia is
      transitory, is related to the rate of foscarnet infusion, and may not be
      reflected as a change in total serum calcium concentration. CONCLUSIONS:
      Foscarnet probably contributed to the neurologic adverse effects reported here.
      Foscarnet may need to be administered at a slower rate than is recommended by the
      manufacturer. Electrolytes must be monitored closely; however, a neurologic
      adverse effect may not be foreseen.

PMID- 7803879
TI  - Triazolam treatment controversy.

PMID- 7803880
TI  - Antioxidants may retard cataract formation.

PMID- 7803881
TI  - Pyridoxine in carpal tunnel syndrome.

PMID- 7803882
TI  - Meropenem: a new carbapenem antimicrobial.
AB  - OBJECTIVE: To describe and then compare an investigational carbapenem antibiotic,
      meropenem, with the only currently available antibiotic in this class,
      imipenem/cilastatin. DATA IDENTIFICATION: An English language search using
      MEDLINE (1988-1993); Abstracts of the 31st Interscience Conference on
      Antimicrobial Agents and Chemotherapy (ICAAC), 1991; and Abstracts of the 32nd
      ICAAC, 1992. STUDY SELECTION: All current scientific publications were reviewed
      for study design and quality. Emphasis was placed on susceptibility and
      pharmacokinetic analysis. Phase 3 clinical trials are now being completed and
      have only been published in abstract form. Hence, conclusions derived regarding
      efficacy were tempered. RESULTS: Meropenem is active against a broad spectrum of
      gram-positive and -negative pathogens including beta-lactamase producers.
      Meropenem appears to be two- to fourfold less active than imipenem against gram
      positive organisms. Meropenem is two- to fivefold more active against
      enterobacteriaceae. The two compounds appear to be equally active against
      Pseudomonas aeruginosa. Pharmacokinetic disposition is also similar for imipenem
      and meropenem. Meropenem may exhibit greater tissue penetration. Meropenem is not
      labile to renal hydrolysis and can be administered without a competitive
      antagonist of dihydropeptidase, such as cilastatin. In clinical trials, meropenem
      appears to be as safe and effective as imipenem/cilastatin or ceftazidime in the
      treatment of infections involving soft tissue, urinary tract, upper respiratory
      tract, abdominal processes, and febrile neutropenic episodes. CONCLUSIONS:
      Meropenem is comparable to imipenem in terms of in vitro susceptibility pattern
      and pharmacokinetic disposition. Overall, meropenem seems to offer promise as the
      second of the carbapenem class of antibiotics. Clinical data are preliminary, and
      further data are needed.

PMID- 7803883
TI  - Busulfan.
AB  - OBJECTIVE: To review the current published studies evaluating the
      pharmacokinetics, clinical efficacy, safety, and toxicity of busulfan in
      pediatric and adult patients. DATA SOURCES: English-language literature published
      between 1953 and 1993 was analyzed; pertinent literature was reviewed. STUDY
      SELECTION: Emphasis was placed on pharmacologic studies and clinical trials
      involving busulfan therapy both in myeloproliferative disorders and in
      conditioning regimens for autologous or allogeneic bone marrow transplantation.
      DATA EXTRACTION: Data from both pediatric and adult studies were evaluated;
      emphasis was placed on the relationship between plasma concentrations of busulfan
      and its efficacy and toxicity. DATA SYNTHESIS: Busulfan has been used widely at
      conventional dosages (1-12 mg/d) for the treatment of patients with chronic
      myelogenous leukemia (CML). Busulfan at high doses (usually 16 mg/kg) given with
      other cytotoxic drugs (especially cyclophosphamide) is a common preparative
      regimen in patients undergoing allogeneic or autologous bone marrow
      transplantation (BMT) for acute or chronic leukemia and other nonmalignant
      disorders (e.g., hemoglobinopathies, inborn error of immune system, congenital
      metabolic disorders). Pharmacokinetics of high-dose busulfan are age-dependent.
      Busulfan systemic exposure and, thus, tissue and tumor exposure are lower in
      children than with adults. Relationships between toxicity (principally
      neutropenia, hepatic veno-occlusive disease, incidence of seizures) and drug
      exposure were found for busulfan. CONCLUSIONS: Busulfan is a useful, sufficiently
      safe drug in the treatment of patients with CML. At higher dosages, busulfan is a
      fundamental part of myeloablative therapies for patients undergoing BMT. As the
      pharmacokinetics and metabolism of busulfan is further understood, there is great
      potential for improving treatment outcome. An assessment of maximal tolerated
      exposure determined by therapeutic drug monitoring may decrease the incidence and
      lethality of regimen-related toxicities.

PMID- 7803884
TI  - Dexrazoxane in the prevention of doxorubicin-induced cardiotoxicity.
AB  - OBJECTIVE: To review doxorubicin-induced cardiotoxicity and to evaluate the use
      of dexrazoxane in its prevention. DATA SOURCES: All animal and human reports
      involving doxorubicin-induced cardiac adverse effects were searched using MEDLINE
      combined with a fan search of relevant papers. DATA EXTRACTION: Animal, in vitro
      cellular, and human data are thoroughly reviewed with particular emphasis on
      doxorubicin-induced cardiotoxicity, including clinical manifestations, risk
      factors, and mechanisms of toxicity. The role of dexrazoxane in the prevention of
      doxorubicin-induced cardiotoxicity is reviewed, including mechanism of effect,
      animal data, and human trials. DATA SYNTHESIS: Anthracyclines are associated with
      a cumulative, dose-dependent, irreversible cardiomyopathy that can lead to
      congestive heart failure and death. The incidence of cardiotoxicity rises sharply
      at a total lifetime dose of more than 550 mg/m2. Through its semiquinone
      metabolite, doxorubicin appears to generate superoxide anion and superhydroxide
      free radicals with iron as a cofactor. Because of poor myocardial concentrations
      of superoxide dismutase, catalase, and glutathione peroxidase, these free
      radicals cause extensive lipid peroxidation and mitochondrial destruction.
      CONCLUSIONS: Dexrazoxane is hydrolyzed to its active form intracellularly and
      binds iron to prevent the formation of superhydroxide radicals, thus preventing
      mitochondrial destruction. The effect of dexrazoxane on the prevention of
      doxorubicin-induced cardiotoxicity is impressive in both animal and human
      studies. Further research is needed to clearly demonstrate the effect dexrazoxane
      has on the antitumor effects of combination chemotherapy while defining optimal
      dosing strategies to minimize myelosuppression and maximize cardioprotection.

PMID- 7803885
TI  - Changing perspectives of stress gastritis prophylaxis.
AB  - OBJECTIVE: To present recent advances in stress gastritis prophylaxis in the
      critically ill and review considerations in selection of a prophylactic agent.
      DATA SOURCES: Information was obtained from MEDLINE search, reference lists from
      articles identified in search, and from review articles. STUDY SELECTION:
      Emphasis was placed on controlled trials conducted within the last 5 years. DATA
      EXTRACTION: All literature was assessed for methodology, results, and
      conclusions. Results of prospective, randomized trials, and meta-analyses are
      summarized. DATA SYNTHESIS: Histamine2-receptor antagonists, antacids, and
      sucralfate appear equally effective in preventing stress gastritis in the
      critically ill. A definitive cause-effect relationship between histamine2
      receptor antagonists and increased incidence of nosocomial pneumonia has not yet
      been established. The indications for using a prophylactic agent and
      consideration in selecting an agent should include an evaluation of the
      following: risk factors for gastritis including the type of intensive care
      patient, comparative efficacy, adverse effects, drug interactions, cost, and ease
      of administration. The least expensive, safest agent requiring minimal monitoring
      is sucralfate. Prevention of stress gastritis has never been shown to reduce
      morbidity or mortality significantly. CONCLUSIONS: Controversies still exist
      regarding the need to provide prophylaxis, the choice of an agent, and the
      relative importance of previously identified risk factors. Further well-designed
      studies are needed before consensus can be reached.

PMID- 7803886
TI  - Acetylcysteine as a cytoprotective antioxidant in patients with severe sepsis:
      potential new use for an old drug.
AB  - OBJECTIVE: To stimulate debate regarding a potential new use for acetylcysteine
      as a cellular antioxidant in severely septic patients with systemic inflammatory
      response syndrome (SIRS). DATA SOURCES: A MEDLINE review of published animal,
      human, and laboratory studies relating to the cytopathogenic effects of active
      radicals in SIRS and the protective effects of acetylcysteine and glutathione.
      STUDY SELECTION: Few studies were available so all studies pertinent to the
      objective were reviewed. DATA EXTRACTION: Clinical and basic science data from
      the available trials of the effects of acetylcysteine on active radical
      production or active radical cell injury were extrapolated to predict the effect
      of acetylcysteine on human sepsis. DATA SYNTHESIS: Severe sepsis is a major cause
      of SIRS. Much of the cellular injury associated with SIRS is mediated by active
      radicals produced by inflammatory cells that overwhelm endogenous antioxidants.
      Reduced glutathione is a crucial intracellular antioxidant that becomes depleted
      during SIRS. Regeneration of glutathione can be achieved by acetylcysteine, which
      unlike glutathione itself penetrates cells. In animal models of sepsis and lung
      injury, acetylcysteine mitigates the cytopathologic effects of SIRS. In humans,
      clinical benefit has been demonstrated in the SIRS of established fulminant
      hepatic failure. CONCLUSIONS: The data do not as yet lead to any firm conclusions
      regarding the value of acetylcysteine in the management of SIRS in severe sepsis.
      The animal and human studies are, however, sufficiently encouraging to warrant
      formal trials to test the hypothesis that acetylcysteine therapy has a
      cytoprotective effect in sepsis.

PMID- 7803887
TI  - Chronic suppurative otitis media.
AB  - OBJECTIVE: To review various aspects of chronic suppurative otitis media (CSOM).
      DATA SOURCES: A MEDLINE search and extensive review of articles provided the
      information for this review. DATA EXTRACTION: Studies describing the
      epidemiology, microbiology, risk factors, pathology, diagnosis, treatment,
      complications, and recurrence of CSOM were included. DATA SYNTHESIS: Pseudomonas
      aeruginosa and anaerobes are the most predominant bacteria found in CSOM.
      Treatment with otic, oral, or parenteral drugs (e.g., neomycin/polymyxin
      B/hydrocortisone otic, ciprofloxacin, ceftazidime, or aminoglycosides) should be
      guided by ear fluid culture results. Prompt treatment with effective and safe
      antibiotics may prevent complications of CSOM. CONCLUSIONS: Treatment of CSOM has
      improved as a result of availability of effective otic and oral antibiotics.
      Treatment of the anaerobic infection with antibiotics should be studied further.

PMID- 7803888
TI  - Salmeterol: its place in asthma management.

PMID- 7803889
TI  - Need for conducting research on medications unlabeled for use in pediatric
      patients.

PMID- 7803890
TI  - Conducting pediatric research.

PMID- 7803891
TI  - Upper gastrointestinal bleeding associated with oral ketorolac therapy.

PMID- 7803892
TI  - Dyspnea and periorbital edema following an increase in naproxen dose.

PMID- 7803893
TI  - Heparin dosing in the morbidly obese patient.

PMID- 7803894
TI  - Fluconazole-warfarin interaction.

PMID- 7803895
TI  - Fluvastatin cost considerations.

PMID- 7803896
TI  - Comment: risk reduction from clinical trials adjusted on an annual basis.

PMID- 7803897
TI  - Comment: niacin, nicotine, and flushing.

PMID- 7803898
TI  - Acute lymphoblastic leukemia. Introduction.

PMID- 7803899
TI  - Genetic changes: relevance for diagnosis and detection of minimal residual
      disease in acute lymphoblastic leukaemia.
AB  - Cure can now be achieved in a proportion of patients with ALL. However, relapse
      and eventual treatment failure occur in many cases receiving identical treatment,
      presumably as a result of failure to eradicate MRD. While for many years marrow
      morphology has been the standard by which leukaemic remission has been assessed,
      more sensitive techniques have been developed for detection of MRD including
      immunophenotypic analysis, and as discussed in this chapter, methods which detect
      leukemia-associated clonal genetic changes at the karyotypic and genomic levels.
      Table 10 lists the applicability and sensitivity of various markers used in MRD
      analysis in ALL. It is apparent that of the karyotypic and molecular approaches
      described, only PCR-based strategies for detection of either leukaemia-specific
      translocations or clonal Ag receptor rearrangements are reliably applicable to a
      high proportion of both B- and T-ALL at sufficiently high sensitivity. Initial
      clinical studies of patients undergoing therapy for ALL using a variety of PCR
      based methods suggest that in some cases a persistent or increasing level of
      residual disease may be predictive for clinical relapse, although a number of
      technical factors and the phenomena of oligo-clonality and clonal evolution may
      limit the usefulness of this analysis in a few instances. From current available
      data it appears that in order to define the potential predictive value of PCR
      detection of MRD a large number of patients will need to be prospectively
      assessed over several years at multiple time points during and after therapy,
      preferably using more than one semi-quantitative PCR approach. In addition to
      reliable prediction of clinical relapse allowing appropriate individual treatment
      modification, progress in the molecular detection of MRD in ALL is also likely to
      be of benefit in the assessment of the efficacy of autograft purging and the
      evaluation of new therapeutic strategies such as the use of biological response
      modifiers to eliminate a low tumour burden.

PMID- 7803900
TI  - Immunophenotypic classification of acute lymphoblastic leukaemia.

PMID- 7803901
TI  - Morphology and cytochemistry of acute lymphoblastic leukaemia.
AB  - ALL is characterized by small to medium sized leukaemic blasts with a rather low
      grade of cell-to-cell variability. The nucleocytoplasmic ratio is high with just
      a small cytoplasmic rim in many cases. The cytoplasm tends to be moderately
      basophilic. Usually, though not in each instance, it is agranular and free of
      vacuoles. The chromatin is more condensed than in AML and the nucleoli tend to be
      indistinct. The FAB classification of haematological malignancies separates ALL
      into three categories: ALL L1, L2, and L3. However, just the identification of
      the L3 variant is of major importance. The L3 cells are medium sized to large and
      are characterized by intensely basophilic and moderately abundant cytoplasm with
      prominent cytoplasmic vacuolation in the bone marrow but not necessarily in the
      peripheral blood. According to our experience there is a high but not universal
      correlation of the L3 phenotype as defined by morphology with the immunologically
      defined B-ALL with surface expression of immunoglobulins. Until recently, acute
      leukaemias proving negative for all cytochemical tests especially for the PAS
      reaction and for the focal type of acid phosphatase, were termed 'acute
      undifferentiated leukaemia' (AUL). However, this morphological/cytochemical
      diagnosis may be confused with the immunological diagnosis of unclassifiable
      leukaemia. Since almost any of these cases can be recognized as ALL or AML by
      immunology, the term AUL should be reserved for cases which can be classified
      neither by morphology/cytochemistry nor by immunology. The morphological and
      cytochemical distinction of ALL from poorly differentiated AML remains a problem,
      especially if the FAB criteria for distinguishing ALL from AML by cytochemistry
      (3% of the blasts positive for peroxidase) are applied rigidly. A small but
      significant percentage of poorly differentiated leukaemias have less than 3% of
      the blasts positive for peroxidase and the myeloid nature of the leukaemia can be
      identified by cytochemistry. The absence of blasts being positive for peroxidase
      is no reliable indicator for the lymphatic nature of a leukaemia, even if the PAS
      reaction is typical for ALL. The morphological diagnosis of ALL needs
      confirmation by immunology in each instance.

PMID- 7803902
TI  - Advances in therapy for childhood non-B-lymphoblastic leukaemia.
AB  - The majority of therapeutic gains for patients with ALL have come from
      prospectively planned clinical trials. Beginning in the 1970s, series of well
      designed protocols have produced valuable information that has permitted the
      development of curative therapy for more than two-thirds of patients. This
      success emphasizes the importance of controlled, carefully analysed therapeutic
      studies, which pay dividends for many years by providing a sound basis for future
      developments. Experienced biostatisticians should be involved early in the
      development of clinical trials to ensure that research questions can be reliably
      answered in terms of the size and composition of the patient sample and in terms
      of accrual time. Despite extensive pre-planning, a protocol may require early
      termination due to unexpected results that compromise the integrity of the
      initial design (Rivera et al, 1985). Thus, periodic treatment assessment of the
      trial is crucial to a successful outcome. Extended follow-up of patients is a
      requirement in every leukaemia study since relapses may occur many years after
      diagnosis, especially if patients have a lower risk of treatment failure (Rivera
      et al, 1979). The quality of long-term survival must also be well documented
      because all protocols include toxic therapy (Ochs and Mulhern 1988). Every
      physician treating children with ALL would like to select therapy that is both
      effective and well tolerated. Unfortunately, this is not always possible when
      patients have high-risk features. Secondary AML, deaths in remission and fatal
      organ toxicity (Steinherz, 1991c) are equally devastating complications of
      current chemotherapy for ALL, and no single protocol can be recommended over any
      other. Patients with ALL may be equally well served by any of several different
      protocols. The practice of administering 6MP + MTX alone and usually orally as
      continuation treatment has been virtually abandoned. Today, most children receive
      intensified chemotherapy in one schedule or another, including good-risk patients
      on POG protocols who, although treated largely with antimetabolite-based
      programmes, receive high-dose chemotherapy during the initial 6 months of
      treatment. In view of the more favourable results attained with reinduction
      therapy in recent CCG studies, these investigators also recommend such an
      approach for children with better-risk ALL. We fully agree. Regrettably, with the
      success of current regimens for higher-risk ALL, it has not been possible to
      exclude all toxic agents that may induce serious late complications.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7803903
TI  - Therapy and prognostic factors in adult acute lymphoblastic leukaemia.
AB  - In acute lymphoblastic leukaemia (ALL) substantial progress has been achieved
      within the last few years. Complete remission rates up to 95% can now be achieved
      in children and 70-85% in adults; disease free survival rates are 70 and 30%
      respectively. To improve results further high dose treatment has been included,
      particularly to overcome drug resistance and to reach cytostatic levels in the
      sanctuary sites, such as the central nervous system. High dose cytarabine in
      combination with other cytostatic drugs, preferentially anthracyclines, seems to
      be of benefit for high risk adult ALL patients. High dose methotrexate, mostly
      explored in childhood ALL, is now also included in a variety of combinations in
      the treatment of adult ALL, but its effectiveness remains to be established.
      Substantial progress has been achieved in adult T-ALL and B-ALL with survival
      rates of 40-50%. The optimal form and duration of maintenance therapy in adult
      ALL is not yet clear but general omission of maintenance leaves patients with an
      inferior outcome. Which subgroups of adult ALL require maintenance and in what
      form still requires investigation. In recent adult ALL trials with intensive
      chemotherapy similar prognostic factors for disease free survival have emerged.
      Of adverse influence are delayed time to reach CR (more than 4/5 weeks), a high
      initial white blood cell count, higher age (above 50 or 60 years), and probably
      the immunological subtypes pre-T-ALL, pre-B-ALL, My(+)-ALL; of very adverse
      influence in elderly patients is the karyotype t(9;22) or the corresponding
      BCR/ABL gene rearrangement. High risk adult ALL patients with one or more of
      these adverse factors are candidates for allogeneic or autologous bone marrow
      transplantation in first remission. Whether all adult ALL patients are candidates
      for BMT in first CR is currently being explored in large prospective randomized
      trials.

PMID- 7803904
TI  - Therapy of B-cell acute lymphoblastic leukaemia in childhood: the BFM experience.
AB  - In 1981 the BFM group introduced a new treatment strategy for B-ALL based on two
      alternating 5-day courses of chemotherapy delivered in short intervals up to a
      total of eight. The therapy courses were composed of fractionated
      cyclophosphamide, MTX 0.5 g/m2 (24-h infusion), i.t. MTX therapy, and ara-C/VM26
      alternating with doxorubicin. The development of the therapy strategies during
      the subsequent two studies was characterized by shortening treatment duration
      from eight to six courses, and intensification of CNS chemotherapy in study ALL
      BFM-83, and the introduction of HD-MTX (5 g/m2, 24-h infusion) in study ALL-BFM
      86. In study ALL-BFM-81, CNS therapy consisted of ID-MTX in combination with i.t.
      MTX and RX. CNS-positive patients received complete neuroaxis irradiation. In
      study ALL-BFM-83, CNS chemotherapy was intensified by adding dexamethasone, while
      MTX/ara-C were administered intraventricularly. Spinal irradiation for CNS
      positive patients was omitted. In study ALL-BFM-86, i.t. MTX/ara-C/prednisolone
      therapy was introduced in combination with HD-MTX but the intraventricular route
      of drug administration was no longer used. Radiotherapy was omitted completely.
      In all, 87 patients were enrolled, 22 (eight CNS positive) in study ALL-BFM-81,
      24 (seven CNS positive) in study ALL-BFM-83, and 41 (none CNS positive) in study
      ALL-BFM-86. The estimated 5-year duration of EFS was 40% in study ALL-BFM-81, 50%
      in study ALL-BFM-83, and 78% in study ALL-BFM-86 (minimal follow-up 36 months).
      Nineteen of 24 relapses occurred while on therapy or shortly thereafter. In study
      ALL-BFM-81, the CNS was the most frequent site of failure. In ALL-BFM-83 there
      were no isolated CNS relapses but more BM relapses occurred. In ALL-BFM-86
      localized manifestations were the predominant site of failure, no isolated BM
      relapses occurred, and only one CNS relapse was diagnosed. No single parameter
      exerted a consistent influence on outcome with one exception. The presence of
      residual disease after the first two courses was correlated with an increased
      risk of therapy failure. Our conclusions from the three studies are listed below.
      An intensive, short-pulse therapy delivered within a 4 month period is highly
      effective in the treatment of B-ALL. Prolonged therapy duration is of no value.
      In addition to fractionated cyclophosphamide-ifosfamide, a 24-h infusion of HD
      MTX5 g/m2 in conjunction with an i.t. therapy is a very important component for
      prevention of both systemic and CNS relapses.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7803905
TI  - Therapy of Burkitt and other B-cell acute lymphoblastic leukaemia and lymphoma:
      experience with the LMB protocols of the SFOP (French Paediatric Oncology
      Society) in children and adults.
AB  - Burkitt's lymphoma and L3-ALL are different forms of the same disease: B-cell
      disease. Therapeutic improvement has been considerable over the past 10 years. In
      France, four consecutive multicentre LMB studies of the SFOP greatly contributed
      to this improvement. An overall cure rate of 90% can now be achieved in children
      with a short intensive risk adapted polychemotherapy regimen based on high-dose
      fractionated CPM, HD MTX (3 g/m2), Ara-C in continuous infusion. For patients
      with ALL or with CNS involvement, the addition of CNS-directed therapy with a
      higher dose of MTX (8 g/m2), HD Ara-C (3 g/m2 x 4), VP 16, triple intrathecal
      injections and cranial irradiation greatly improved survival: 87% for ALL and 73%
      for patients with CNS involvement. In adults, the application of the paediatric
      protocol is possible with acceptable toxicity and a retrospective study of 41
      cases treated according to a LMB protocol showed a cure rate of 71%. Such a
      regimen should now be proposed to adults and studied prospectively.

PMID- 7803906
TI  - Central nervous system directed therapy in acute lymphoblastic leukaemia.
AB  - CNS-directed treatment is an essential component of therapy for both children and
      adults with acute lymphoblastic leukaemia. The choice between combinations of
      i.t. drugs, radiotherapy and high-dose systemic chemotherapy is not a clear one
      and will depend on the age of the patient, the type of leukaemia and indeed the
      available treatment facilities. A plea is made for any prospective trials of CNS
      directed therapy to incorporate formal assessment of neuropsychological
      performance, and in the young child, of growth and pubertal progression.

PMID- 7803907
TI  - Long-term sequelae of therapy for childhood acute lymphoblastic leukaemia.
AB  - Childhood ALL has provided the model for basic therapeutic principles in the past
      and now provides the model for late effects studies. Common threads which run
      throughout the literature in this area of clinical research are the importance of
      young age with increased vulnerability to long-term treatment induced sequelae
      and the relatively large contribution of radiation as compared with chemotherapy
      in the pathogenesis of adverse sequelae. Previous retrospective studies of long
      term childhood ALL survivors focused on neuropsychologic changes and anatomic
      changes in the CNS after cranial irradiation. More recent retrospective studies
      have made the following new observations: (i) the high frequency of significant
      short adult stature in those less than 6 years of age at diagnosis who received
      24 Gy cranial irradiation; (ii) actuarial risk of 2.5% of developing a second
      malignancy with approximately one-half of secondary malignancies occurring in the
      CNS in children 5 years of age or less who received cranial irradiation; (iii)
      the association of secondary ANLL with epipodophyllo-toxin use, and (iv) delayed
      cardiac toxicity despite anthracycline dosage reduction. Current therapy
      regimens, especially in high-risk patients, are both more successful and more
      intensive than those used in the past. While it will be another decade before
      many of the long-term sequelae begin to emerge, one can anticipate, based on
      current experience, some of the problems that will occur.

PMID- 7803908
TI  - Bone marrow transplantation for acute lymphoblastic leukaemia.
AB  - Allogeneic bone marrow transplantation (BMT) has been used in the treatment of
      poor risk acute lymphoblastic leukaemia (ALL) for over 20 years. Over this period
      results have improved and indications for treatment have become more clearly
      defined. Over 60% of adults and over 70% of children with poor risk ALL in first
      remission, and 30-40% of patients in second remissions can be expected to achieve
      long term leukaemia-free survival. Factors implicated in the cure of ALL by BMT
      are the myeloablative preparative regimen, a graft-versus-leukaemia effect, and
      post transplant chemotherapy. Improved results of chemotherapy have changed the
      perceived indications for BMT in ALL and have led to controversy over the best
      treatment approach. However there is good evidence to show that BMT offers a
      better chance of leukaemia free survival in certain very poor risk categories.
      These include Philadelphia chromosome positive ALL, remission induction failures,
      and children in second remission who relapse after adequate chemotherapy.
      Particular issues in the use of BMT in ALL are the prevention and management of
      extramedullary leukaemia, the treatment of relapse following BMT, and the
      prevention and monitoring of late effects. In the future the use of unrelated
      donors, and a continuing fall in transplant related morbidity and mortality will
      extend the use of BMT in poor risk ALL.

PMID- 7803909
TI  - Autologous bone marrow transplantation in acute lymphoblastic leukaemia.
AB  - The purpose of this review is to assess the current status of autografting in
      acute lymphoblastic leukaemia. In the first part of the review, the prognostic
      factors are discussed. Only the studies that contained adequate response and
      survival data were selected for analysis, including peer-reviewed articles, book
      chapter and proceedings of international meetings. The most current and complete
      references were used for series reported more than once. In the second part, some
      areas of discussion and controversy, such as the timing of autografting and the
      role of marrow purging are argued. In the last part of this review we have
      discussed our recent experience with blood progenitor cells collected during
      early haemopoietic function restoration after intensive conventional treatment
      for patients with cytogenetic abnormalities. The first preliminary results seem
      highly interesting and confirm our results achieved with the same procedure in Ph
      positive chronic myelogenous leukaemia.

PMID- 7803910
TI  - Interleukin-2 and gene therapy in the management of acute lymphoblastic
      leukaemia.
AB  - The overall unfavourable prognosis of adult acute leukaemia patients has prompted
      the search for alternative therapeutic strategies. Probably the most sought
      challenge, which over the years has been met by consistent disillusion, has been
      immunotherapy. With little doubt the goal of stimulating the immune system of the
      host in the hope of controlling or eradicating residual disease following more
      conventional ablative regimens, remains conceptually a highly desirable approach.
      During the last few years an innovative strategy, based on the in vitro
      demonstration that IL2 is capable of inducing a previously unrecognized cytotoxic
      function directed against primary tumours and named LAK, has been applied with
      some success in solid tumour patients. Here, we shall review the pre-clinical
      data which indicate that IL2-based immunotherapy may be employed also in the
      management of patients with acute leukaemia. Clinical data which support a
      possible in vivo antileukaemic effect of IL2 are presented. The
      clinicohaematological modifications, as well as the biological modulations
      induced in the patients following the administration of IL2 are also discussed.
      In view of the recent demonstration that the IL2 gene can be successfully
      transduced into human neoplastic cells, we finally discuss the rationale of gene
      transfer approaches in an attempt to overcome some of the limitations associated
      with the administration of high doses of exogenous IL2.

PMID- 7803911
TI  - Clinical significance of necrosis in lupus nephritis.
AB  - The significance of necrosis (karyorrhexis), among the most characteristic
      findings in lupus nephritis, was evaluated by studying the correlation between
      the existence of necrosis in renal biopsy specimens and laboratory findings. The
      subjects were 54 patients with diffuse proliferative lupus nephritis and 6
      patients with focal proliferative lupus nephritis selected from 143 patients with
      lupus nephritis. We also compared the clinical course of oral prednisolone and
      intravenous methylprednisolone pulse therapies after steroid administration.
      Compared with the non-necrosis group, the necrosis group had significantly lower
      CH50 levels and more proteinuria. Patients with necrosis were effectively treated
      with repeated pulse therapy judging by immunological activity and the decrease in
      proteinuria at an early stage, but responded poorly to oral steroid therapy. As
      the presence of necrosis in cases of lupus nephritis means high immunological
      activity of the lesion and there is responsiveness to a large dose of steroids,
      extensive immunosuppressive therapy including methylprednisolone pulse therapy
      should be applied to these patients.

PMID- 7803912
TI  - Inhibition of collagen production by traditional Chinese herbal medicine in
      scleroderma fibroblast cultures.
AB  - The in vitro effect of one traditional Chinese herbal medicine (Japanese name:
      "Keishi-bukuryo-gan"), which has been empirically used in scleroderma patients in
      China and Japan, on collagen production in fibroblast cultures was studied.
      Fibroblasts from 3 scleroderma patients and 2 normal controls were incubated with
      various concentrations of "Keishi-bukuryo-gan" and collagen production was then
      determined by a radiochemical method. "Keishi-bukuryo-gan" significantly and
      selectively inhibited collagen synthesis in a dose-dependent manner, with a
      tendency of a stronger effect on scleroderma fibroblasts than control cells. The
      results may explain the clinical usefulness of this medicine, and it may become a
      promising new agent for the treatment of scleroderma.

PMID- 7803913
TI  - Hemichorea in hyperglycemia associated with increased blood flow in the
      contralateral striatum and thalamus.
AB  - We studied a patient with hyperglycemia who developed choreic involuntary
      movements in the right extremities using single photon emission computed
      tomography (SPECT) with 123I-N-isopropyl-p-iodoamphetamine. SPECT revealed an
      increased blood flow in the left striatum and thalamus. Through the control of
      blood glucose and the administration of haloperidol, the hemichorea was resolved,
      and the increased blood flow in the striatum and thalamus disappeared. These
      findings suggest that the increased blood flow, which probably indicates
      increased neuron activity in the striatum and thalamus, is an underlying
      pathophysiological state in hemichorea.

PMID- 7803914
TI  - Locked-in syndrome and abnormal orientation of the right vertebral artery in a
      young man.
AB  - A 35-year-old man developed a cerebral infarction and experienced transient
      ischemic attacks originating from the vertebrobasilar artery, as well as locked
      in syndrome. He recovered with minimal neurological deficit. On cerebral
      angiography, the orientation of the right vertebral artery was markedly abnormal
      as it entered the foramina of the transverse process at the level of the third
      cervical vertebra. We concluded that the abnormal orientation of the vertebral
      artery caused the thrombosis and that the transient ischemic attacks, locked-in
      syndrome and cerebral infarction were brought about by thromboemboli originating
      in this artery.

PMID- 7803915
TI  - Acute pneumonitis presumed to be silicone embolism.
AB  - A 39-year-old housewife who underwent intramammary injections of a proprietary
      silicone fluid mixture showed clinical and novel transbronchial lung biopsy
      (TBLB) findings. She presented with complaints of progressive dyspnea, dry cough,
      and pleuritic chest pain 2 days after the last silicone injections. The chest X
      ray and CT scan showed diffuse interstitial infiltrates. TBLB demonstrated
      translucent, presumably silicone globules embolized within the pulmonary
      capillaries. The documentation of intramammary injections, the clinical and
      radiographic features of acute pneumonitis, and the histopathologic evidence by
      TBLB, may support the causal relationship between illicit injections and the
      silicone embolism. We discuss the pathogenesis and urge that this potentially
      toxic source of pulmonary embolism be removed.

PMID- 7803917
TI  - IgA nephropathy associated with portal hypertension in liver cirrhosis due to non
      alcoholic and non-A, non-B, non-C hepatitis.
AB  - A 69-year-old female was admitted to our hospital because of leg edema,
      proteinuria (2.1 g/day), and gross hematuria. She had non-alcoholic liver
      cirrhosis of unknown etiology. Esophageal varices also were found. Examination of
      the renal biopsy specimen revealed mesangial proliferative glomerulonephritis
      with IgA deposits. Propranolol was administered orally to reduce portal
      hypertension, resulting in a progressive decrease in urinary microalbumin
      excretion. This case suggests that portal hypertension is involved in the
      pathogenesis of IgA nephropathy in liver cirrhosis.

PMID- 7803916
TI  - Renal thrombotic microangiopathy in a patient with rheumatoid arthritis and
      antiphospholipid syndrome: successful treatment with cyclophosphamide pulse
      therapy and anticoagulant.
AB  - A female patient with a history of migraines and chorea developed polyarthralgia
      at age 24 and was diagnosed with rheumatoid arthritis. In 1991 she was
      hospitalized because of impaired renal function and hypertension. Examination
      revealed thrombocytopenia and the presence of lupus anticoagulant. Antinuclear
      antibody was weakly positive, but anti-DNA antibody was negative, and no decrease
      in leukocyte count or complement level was observed. Rheumatoid arthritis with
      antiphospholipid syndrome was diagnosed. Renal biopsy showed renal thrombotic
      microangiopathy. This renal lesion was considered to be associated with
      antiphospholipid syndrome. Cyclophosphamide pulse therapy and anticoagulation
      therapy decreased proteinuria and improved renal function.

PMID- 7803918
TI  - Acquired idiopathic pure red cell aplasia in a hemodialyzed patient with inactive
      systemic lupus erythematosus.
AB  - A male patient suffered chronic renal failure due to lupus nephritis and was
      undergoing hemodialysis. Six years after beginning hemodialysis, anemia
      developed, which improved by erythropoietin. Unresponsiveness to erythropoietin
      gradually appeared, and with a suspicion of pure red cell aplasia, he was treated
      with a high-dose corticosteroid but the unresponsiveness did not improve. Neither
      his serum nor lymphocytes inhibited erythropoiesis of either normal bone marrow
      stem cells or his own in vitro. These observations suggest an impaired
      hematopoietic microenvironment in his bone marrow.

PMID- 7803919
TI  - Good's syndrome with a block in the early stage of B cell differentiation and
      complicated by Campylobacter fetus sepsis.
AB  - A 63-year-old man was admitted for Campylobacter fetus sepsis and
      immunodeficiency syndrome with thymoma (Good's syndrome). Serological examination
      demonstrated hypoimmunoglobulinemia. Analysis of lymphocyte subsets in the
      peripheral blood and bone marrow showed marked decreases in the proportion of
      cells bearing B cell markers. However, there were no abnormalities of cellular
      immunity. This is a rare case of Good's syndrome in Japan in which the pathogenic
      mechanism involved a block in the early stage of B cell differentiation.
      Moreover, this is the first case ever reported of Campylobacter fetus sepsis
      associated with Good's syndrome.

PMID- 7803920
TI  - Syndrome of inappropriate secretion of ADH (SIADH) due to small cell lung cancer
      with extremely high plasma vasopressin level.
AB  - A 76-year-old man with small cell lung cancer associated with the syndrome of
      inappropriate secretion of ADH (SIADH) visited our hospital. The serum Na level
      was normal on the first visit, but 2 weeks later it decreased to 114 mEq/L with
      an extremely high plasma vasopressin (VP) level of 1520 pg/ml. Serum Na was
      normalized after the reduction of the tumor size by chemotherapy, but the plasma
      VP level remained between 150 to 600 pg/ml. On gel filtration of plasma VP two
      peaks of immunoreactive VP were eluted at the positions of a larger molecule than
      authentic VP and authentic VP, and VP in urine gave only one peak compared to
      that of authentic VP. The dilution curve of plasma VP was almost parallel and
      that of urine was completely parallel to the standard curve. These findings
      suggest that a larger VP with low physiological activity was predominantly
      secreted in the present patient and manifested relatively mild symptoms despite
      the extremely high plasma VP level.

PMID- 7803921
TI  - Sjogren's syndrome in one of two sisters with idiopathic renal hypouricemia.
AB  - Concomitance of idiopathic hypouricemia and Sjogren's syndrome is reported. A 37
      year-old Japanese woman with Sjogren's syndrome and her 39-year-old sister
      without this syndrome both had extremely low levels of serum uric acid. Markedly
      increased urinary excretion of uric acid and poor response to the pyrazinamide
      suppression test revealed that the hypouricemia in these sisters was caused by a
      defect in the pre-secretory reabsorption of uric acid. It is categorized as
      idiopathic renal hypouricemia than hypouricemia rather secondary to Sjogren's
      syndrome. Thus, idiopathic renal hypouricemia should be considered even in cases
      with autoimmune diseases.

PMID- 7803922
TI  - Deficiency of the fourth component of complement (C4): a family case.
AB  - In this report, an apparently healthy 38-year-old woman with a remarkably low
      serum C4 value is described together with other family members who had moderately
      low serum C4. Plasma C4 typing disclosed that the proband inherited two C4B
      "null" haplotypes. In addition, Southern blot analysis of the C4 gene indicated
      that the C4A gene was partially deleted on one of these two haplotypes in the
      proband. We thus concluded that a de novo deletion on the inherited half-null
      haplotype was the likeliest cause of the low C4 level.

PMID- 7803923
TI  - Alcaptonuria: a case complicated with valvular heart disease and
      immunodeficiency.
AB  - A 75-year-old man was diagnosed with alcaptonuria by direct identification of
      homogentisic acid in the urine using gas chromatography-mass spectrometry.
      Complications included valvular heart disease with marked calcification detected
      by two-dimensional color-Doppler echocardiography and recurrent bacterial
      infection. Immunological analyses revealed a reduced number of T cells with
      compensatory expansion of CD56+, CD57+ natural killer (NK) cell population and
      impaired functions of cellular immunity such as phytohemagglutinin response,
      antibody-dependent cellular cytotoxicity, NK activity and interleukin-2
      production. Humoral immunity and neutrophil functions were considered to be
      normal. This is the first reported case of alcaptonuria to our knowledge in which
      immunological abnormality was documented.

PMID- 7803924
TI  - Treatment of fungal infections in patients with HIV-infection or AIDS.

PMID- 7803925
TI  - No cultural detection of Helicobacter pylori in dental plaque.
AB  - Helicobacter pylori causes human type B gastritis and is involved in the etiology
      of peptic ulcer disease. The routes of transmission of H. pylori are still
      unclear. The microorganism may be transmitted orally, since H. pylori has been
      detected in dental plaques. To confirm the hypothesis that dental plaques are a
      reservoir of H. pylori, 100 dental plaque specimens from 55 dental surgery
      patients were incubated on one nonselective and up to four selective agar media
      for the detection of H. pylori. In addition, urease activity of the plaque
      material was tested, and the gingival status of the patients was assessed. H.
      pylori was not cultivated from any of the specimens investigated. Plaque material
      from 12 patients with moderate and severe gingivitis showed urease activity. The
      results do not confirm the hypothesis that dental plaques are a relevant
      reservoir of viable H. pylori cells. However, non-cultivatable forms of H. pylori
      may survive in dental plaques. Urea cleaving activity of dental plaque may be a
      marker of gingival inflammation.

PMID- 7803926
TI  - Seventy colicin types of Shigella sonnei and an indicator system for their
      determination.
AB  - An extended scheme of colicin typing of Shigella sonnei strains includes 70
      colicin types. Colicin type No. 56 is the producer of a new colicin, for which T
      marking was proposed. A total number 105 of indicator strains was prepared for
      typing.

PMID- 7803927
TI  - Influence of the glucose concentration on the yield of biomass and
      lipopolysaccharide in Salmonella cultures.
AB  - Two Salmonella S-forms and two R-mutants were cultivated in complex medium
      supplemented with different amounts (0.5-3%) glucose. Cultivation was performed
      batchwise in a fermentor under aerobic conditions. With all strains investigated,
      the yield of bacterial mass increased with increasing concentration of glucose.
      In the case of three strains, the % LPS content of bacteria also increased, thus
      achieving the aim of this investigation. The synthesis of bacterial mass and LPS
      did not proceed in parallel and differed from strain to strain. At optimal
      glucose concentration, the yield of LPS could be increased up to 250%. The
      chemical composition of the LPS was independent of the glucose concentration. The
      individual strains exhibited an identical composition with regard to lipid A and
      polysaccharide when cultured at different glucose concentrations. The uniformity
      of the molecular distribution of LPS could also be confirmed by SDS
      polyacrylamide gel electrophoresis. In the S-form LPSs, also the proportion of
      the unsubstituted R-form LPS was not affected by the glucose concentration in the
      culture medium. The present results demonstrate that optimisation of the
      cultivation conditions with respect to the glucose concentration of the medium
      would be of advantage especially for Salmonella strains that are cultivated
      frequently.

PMID- 7803928
TI  - Serovars of Plesiomonas shigelloides.
AB  - Among 391 P. shigelloides strains, 330 were typable and found to belong to 43 O
      serovars. The most frequent O serovars were O17 (23%), O32 (7%), O12 (4.5%) and
      O5, O18 and O44 (3.8% each). The majority of the serovars represented, with
      almost 300 strains, were sporadically found in very distant countries of three
      continents (Europe, Asia, America), whereas only one serovar (O68) was isolated
      three times in one single district of South Bohemia (Ceske Budejovice). It
      suggests that such an incidence of plesiomonads is only seemingly sporadic and
      that there must be many strains which are not detected owing to the imperfect
      cultivation methods used so far.

PMID- 7803929
TI  - Isolation and partial characterization of the major protein of the outer membrane
      of Pasteurella haemolytica and Pasteurella multocida.
AB  - The N-terminal amino acid sequence of the 35 kDa (p35) major outer membrane
      protein (MOMP) of P. multocida shared a strong homology with those of
      homotrimeric nonspecific porins of gram-negative bacteria. The capacity of outer
      membrane protein (OMP) preparations of P. multocida to bind to respiratory
      mucosal surface preparations was inhibited significantly by using a polyclonal
      anti-p35 antiserum in an adhesion ELISA. Anti-p35 antiserum cross-reacted with a
      44 kDa (p44) MOMP of P. haemolytica. N-terminal sequencing of MOMP p44 revealed a
      homology of 81% with the putative porin MOMP p35 of P. multocida.

PMID- 7803930
TI  - Typing of Shigella dysenteriae strains of different serogroups by lectins.
AB  - Ten different serogroups of Shigella dysenteriae were typed with the aid of
      lectins of known sugar specificity resulting from their interactions with the
      carbohydrates on lipopolysaccharides in the outer membrane of bacteria as
      evidenced by the agglutination-inhibition assay with simple carbohydrates.
      Lipopolysaccharides of two serogroups of Shigella were precipitated with
      different lectins and the results were corroborated by those derived from the
      agglutination assay suggesting that Shigella dysenteriae can be characterized on
      the species level with the aid of lectins.

PMID- 7803931
TI  - Monoclonal antibody based competitive ELISA for the detection of specific
      antibodies against Coxiella burnetii in sera from different animal species.
AB  - A competitive ELISA system for the detection of antibodies against Coxiella (C.)
      burnetii in cattle, sheep, goats, horses and humans is described. The ELISA is
      based on a biotinylated monoclonal antibody with specificity for C. burnetii
      lipopolysaccharide in combination with streptavidin peroxidase. For evaluation
      and statistical analysis, 413 sera from cattle, sheep, goats, horses and humans
      were tested in parallel in the indirect immunofluorescence test (IFT).
      Furthermore, a total of 448 bovine and human sera were also tested with an
      indirect ELISA and 47 sheep sera were investigated using the commercially
      available "Ridascreen AK EIA". Sensitivity and specificity values for the
      competitive ELISA described and determined with the aid of the indirect
      immunofluorescence test (IFT) as reference were: cattle, 88% and 89%; sheep, 100%
      and 93%, goat, 82% and 96%, horse 100% and 93%, and man 42% and 96%,
      respectively.

PMID- 7803932
TI  - Differentiation of selected members of the family Neisseriaceae (Alysiella,
      Eikenella, Kingella, Simonsiella and CDC groups EF-4 and M-5) by carbohydrate
      fingerprints and selected phenotypic features.
AB  - On the basis of nucleic acid relationships, the family Neisseriaceae consists of
      the genera Neisseria, Kingella, Simonsiella and of Alysiella filiformis,
      Eikenella corrodens, and the CDC groups EF-4 and M-5. Differentiation, especially
      of the new members of the family, by conventional phenotypic characteristics is
      difficult and in some cases leads to doubtful results. On the other hand,
      cellular components proved to be suitable for the characterization of bacterial
      taxa. We investigated the cellular carbohydrates derived from whole cell
      hydrolysates of the above mentioned taxa with the exception of Neisseria by gas
      chromatography/mass-spectrometry. The analysis revealed characteristic patterns
      for all taxa considered, although with some species of which only few strains
      were investigated so far only preliminary results could be established. With the
      method used, the carbohydrate analysis could be completed within six hours
      starting from a pure culture. All strains investigated exhibited a common pattern
      with ribose, arabinose, glucose, and galactose. Qualitative and quantitative
      differences in contents of fucose, sorbose, rhamnose, threose, heptose,
      galactosamine and an amino sugar similar to glucosamine discriminated members of
      the taxa investigated. To achieve a taxonomically precise differentiation of the
      species investigated by conventional phenotypic features as available in
      commercial rapid test kits, these tests should be completed by the carbohydrate
      analysis technique presented.

PMID- 7803933
TI  - Purification and partial characterization of type 3 fimbriae from Salmonella
      typhimurium var. copenhagen.
AB  - Aggregative thin fimbriae from a pigeon pathogen, Salmonella typhimurium var.
      copenhagen (STMVC) Mo 8 were isolated and purified. These fimbriae remained
      associated with the cells even after attempts to separate them from blended cells
      by centrifugation. After purification, fimbriae and little cell fractions were
      polymerized in formic acid and then analyzed by SDS-PAGE. This pretreatment
      resulted in the appearance of a main protein band of 17 kDa. The N-terminal amino
      acid sequence of 19 residues of purified 17 kDa protein showed considerable
      homology with the N-terminal sequence of thin fimbriae of S. enteritidis. Native
      fimbriae on whole cells were specifically labelled with immune serum raised to
      the purified fimbriae. This immune serum also reacted with the denatured 17 kDa
      protein in Western blots. The polyclonal immune serum did not cross-react with
      the type-1 fimbriae produced by STMVC.

PMID- 7803934
TI  - Antibacterial efficacy of ciprofloxacin in a case of endocarditis due to
      Cardiobacterium hominis.
AB  - Endocarditis due to Cardiobacterium hominis is rare and may be treated with a
      variety of antibiotics. We isolated the bacteria from blood cultures of a patient
      with Cardiobacterium hominis endocarditis who could be successfully treated with
      ciprofloxacin. The bacterial features of Cardiobacterium hominis are presented,
      and susceptibility to ciprofloxacin is documented with bacterial killing curves
      employing peak and trough specimens of patient's serum.

PMID- 7803935
TI  - Serological analysis by A60 antigen ELISA and BCG immunoblotting in domestic
      carnivores experimentally vaccinated with mycobacterium bovis BCG.
AB  - The serological response to Mycobacterium bovis BCG vaccination was studied in 3
      cats, 3 dogs and 3 puppies. The animals received two doses of 0.1 mg of BCG and
      were studied over a period of 8 months simultaneously by ELISA with antigen A60
      (Anda Biologicals, Strasbourg, France) and immunoblotting with BCG. The two
      methods detected an increase of antibodies at 3 or 5 weeks. In the cats, specific
      antibody titer remained high and stable for more than one year, in the dogs they
      diminished quickly within 23 weeks. Carnivores elicit a serological response
      against specific protein antigens in the bands corresponding to 18 and 25kDa, 30
      and 45kDa, and especially 35 and 42kDa bands, and to minor bands at higher
      molecular weight. Non-specific bands at 50-55 kDa and 70 kDa, assigned to heat
      shock proteins, were enhanced by BCG vaccination. Cat immunosera recognized on
      A60 immunoblots the specific homologous bands at 20-25 kDa and 32 kDa, but also
      two other dominant bands: one was partially specific (65 kDa) and the other was
      absent from the M. bovis and M. paratuberculosis profiles. The suitability of A60
      ELISA for detection of mycobacterial infection in carnivores may be highlighted
      by immunoblot analysis.

PMID- 7803936
TI  - Detection of antibodies to defined M. tuberculosis antigen (38 kDa) in
      cerebrospinal fluids of patients with tuberculous meningitis.
AB  - Antibodies to the 38 kDa antigen of M. tuberculosis which is serospecific to the
      tuberculosis complex group of organisms was studied in CSF samples of patients
      with tuberculosis meningitis. Patients were classified into four groups, viz.
      post-mortem-proved, culture-proved, clinically suspected and tuberculoma. Anti-38
      kDa antibody was detected by ELISA and was positive in 60%, 80% 62.5% and 0%,
      respectively in the four groups. Controls showed a false-positive detection of
      5%. Follow-up of patients was done up to 6 weeks and antibody levels dropped in
      all the patient groups.

PMID- 7803937
TI  - Psychosocial interventions in the management of recurrent headache disorders. 1:
      Overview and effectiveness.
AB  - This is the first in a series of three articles addressing nonpharmacologic
      therapies for management of recurrent migraine and tension-type headache. It
      provides an overview of the commonly employed nonpharmacologic therapies for
      recurrent headache, reviews scientific evidence of their efficacy, and identifies
      the psychosocial interventions that have the greatest potential to enhance the
      management of recurrent migraine and tension-type headache in primary care
      settings internationally. In the second article, the authors offer practical
      guidelines for the administration of recommended nonpharmacologic interventions.
      The third article explores healthcare policy implications involved in a decision
      to incorporate psychosocial interventions into primary care practice.

PMID- 7803938
TI  - Psychosocial interventions in the management of recurrent headache disorders. 2:
      Description of treatment techniques.

PMID- 7803939
TI  - Psychosocial interventions in the management of recurrent headache disorders. 3:
      Policy considerations for implementation.

PMID- 7803940
TI  - Cardiovascular conditioning and anticipatory nausea and vomiting in cancer
      patients.
AB  - Explanations of individual differences in susceptibility to learning of
      anticipatory nausea and/or vomiting (AN/V) in cancer patients have focused mainly
      on the patients who develop AN/V. On the basis of conditioning theory, however,
      one would expect that all patients who experience post-treatment nausea and/or
      vomiting (PN/V) should develop AN/V. Consistent with findings demonstrating that
      conditioned responses are more easily established in autonomic-reactive
      individuals, we have previously reported that patients who do not develop AN/V
      (noAN/V) are less autonomic reactive than the AN/V patients. Thus, we
      hypothesized that the noAN/V patients might not show classical conditioning to
      the same degree and extent as the AN/V patients and that conditioning may be the
      mediating mechanism in AN/V. This study presents data from 36 patients. Among the
      28 patients who experienced PN/V, 16 developed AN/V. We found no systematic group
      differences in severity of PN/V or antiemetic treatment. Before chemotherapy, all
      patients were tested in a signaled reaction-time paradigm. We used two different
      tones (CSs), one of which was always followed by a noise (UCS) as a button-press
      signal. The patients who later developed AN/V demonstrated significantly shorter
      reaction times, and also showed enhanced cardiovascular reactivity to the tone
      followed by the UCS (CS+) in comparison with the nonsignal tone (CS-). The noAN/V
      patients did not show differential cardiovascular responses to the CS+ and CS-.

PMID- 7803941
TI  - Are there different determinants of the frequency, intensity, and duration of
      physical activity?
AB  - The authors of this study explored whether different determinants exist for each
      of the three components of physical activity (frequency, intensity, and
      duration). The theoretical model they used was a modified version of the theory
      of planned behavior. Undergraduate volunteers (N = 170) completed an initial
      questionnaire and provided self-reports 2 and 4 weeks later of their physical
      activity during the interval. Hierarchical regression analyses indicated that
      both intention and self-efficacy explained unique variance in frequency and
      intensity, but only intention explained unique variance in duration. Further
      hierarchical regression analyses showed that self-efficacy contributed unique
      variance to all three components of intention, whereas attitude was implicated
      only in intended frequency and duration, and affect only in intended intensity.
      Possible explanations for the emergence of different determinants of the three
      components are discussed, and directions for future research are suggested.

PMID- 7803942
TI  - Sympathomimetic drug abuse masking an endogenous hyperadrenergic state, Graves'
      disease.
AB  - Sympathomimetic drug use or abuse in a thyrotoxic individual can be clinically
      devastating as a result of enhanced cellular sensitivity to adrenergic
      stimulation. Thus, it is critical to recognize thyrotoxicosis in a patient with
      coexistent sympathomimetic drug abuse. This case report describes a patient with
      Graves' disease and severe hyperadrenergic symptomatology that was thought to
      result from sympathomimetic drug abuse.

PMID- 7803943
TI  - Is the acute physiology and chronic health evaluation (APACHE) scale agist?
      Therapeutic implications in older patients.

PMID- 7803944
TI  - Pharmacological advances in the treatment of glaucoma.
AB  - Glaucoma is a potentially blinding disease. The goal of glaucoma therapy is to
      reduce intraocular pressure to a predetermined target level. There are currently
      5 classes of compounds used for the medical management of glaucoma. Four classes
      that appear promising for the long term management of glaucoma are in different
      phases of clinical investigation, and include the topically active carbonic
      anhydrase inhibitors, selective alpha 2-adrenergic agonists, prostaglandins and
      ethacrynic acid. The topically active carbonic anhydrase inhibitor dorzolamide
      (MK-507) is effective and well tolerated in clinical trials of up to 1 year's
      duration. Animal studies have demonstrated that this drug lowers intraocular
      pressure by reducing aqueous humour formation. The selective alpha 2-adrenergic
      agonists, brimonidine and apraclonidine, have been shown to be effective in
      reducing intraocular pressure in the short term. Long term effectiveness of these
      agents is under investigation. Prostaglandins (PG) of the PGF2-alpha
      isopropylester series caused marked reductions of intraocular pressure in
      laboratory and clinical trials. The newest prostaglandin analogue, latanoprost
      (PhXA41), effectively lowered intraocular pressure and was well tolerated in
      clinical trials of up to 4 weeks' duration. Prostaglandins reduce intraocular
      pressure by enhancing uveoscleral outflow. Ethacrynic acid enhanced traditional
      outflow facility and lowered intraocular pressure when applied topically or
      intracamerally in laboratory studies and clinical trials. Corneal adverse effects
      of ethacrynic acid have been noted. Reformulation of ethacrynic acid ointment may
      resolve this problem. These 4 classes of compounds will enhance our options for
      the medical management of glaucoma. They may be used instead of or in combination
      with some of the drugs currently in use, and may be better tolerated.

PMID- 7803945
TI  - The Hypertension in the Very Elderly Trial (HYVET). Rationale, methodology and
      comparison with previous trials.
AB  - The Hypertension in the Very Elderly Trial (HYVET) is a multicentre, open,
      randomised, controlled trial. The aim of this trial is to investigate the effect
      of active treatment on stroke incidence in hypertensive patients over the age of
      80 years. Secondary end-points include total cardiovascular mortality and
      morbidity. Entry criteria include a sustained sitting systolic blood pressure of
      160 to 219mm Hg plus a sustained sitting diastolic pressure of 95 to 109mm Hg.
      Also required is a standing systolic blood pressure of at least 140mm Hg.
      Patients must give their informed consent, and be free of congestive heart
      failure requiring treatment, gout, renal failure or a recent cerebral
      haemorrhage. Patients are to be randomised to 3 groups-(i) no treatment; (ii)
      treatment with a diuretic [bendroflumethiazide (bendrofluazide)]; or (iii)
      treatment with an angiotensin converting enzyme (ACE) inhibitor (lisinopril).
      Starting dosage for bendroflumethiazide and lisinopril is 2.5 mg/day. In order to
      achieve goal sitting systolic and diastolic blood pressures (< 150/80 mm Hg), a
      doubling of the dosage is allowed. Furthermore, slow release diltiazem (120
      mg/day increasing to 240 mg/day if required) may be added to the medication of
      the actively treated groups. These drugs have been chosen as inexpensive and
      appropriate representatives of their therapeutic classes. 700 patients in each
      group (a total of 2100) will be sufficient to detect a 40% difference in
      cerebrovascular events between no treatment and active treatment (alpha = 0.01, 1
      beta = 0.90). These numbers will also detect a difference in total mortality of
      25% and in cardiovascular mortality of 35%. The pilot phase of the trial has been
      started with support from the British Heart Foundation. Centres which are
      interested in taking part should contact C.J. Bulpitt or any of the other
      authors.

PMID- 7803946
TI  - Prognostic significance of blood pressure in the very old. Implications for the
      treatment decision.
AB  - A positive relationship between blood pressure and mortality at the age of 60 to
      69 years becomes a negative relationship in men over the age of 75 years and in
      women over the age of 85 years, with hypertensive individuals living longer. This
      negative relationship in very old people probably reflects cardiac, respiratory
      and neoplastic disease in those with low blood pressure, and good myocardial
      function in those with high blood pressure. Therefore, in very elderly
      hypertensive people we cannot conclude that a reduction in blood pressure will
      not be beneficial, e.g. in reducing stroke events. However, the results of
      clinical trials of antihypertensive treatment in the elderly provide inadequate
      evidence to assess the benefit of treating hypertensive individuals over the age
      of 80 years. Randomly allocated controlled trials are required in this age group.
      The antihypertensive treatments that may be most suitable for the very elderly
      are diuretics with a beta-adrenergic blocking drug added if necessary.
      Angiotensin converting enzyme (ACE) inhibitors and calcium channel blockers have
      not, as yet, a proven role in the treatment of hypertension in the very old.

PMID- 7803950
TI  - [Complementary or subsidiary--why do we actually need the public health office?].
AB  - The public health service likes to describe itself as a kind of "third pillar",
      which together with the two other "pillars"--out-patient and in-patient care-
      supports the system of health service of the FRG. In fact, in the years since
      1945 no health or sociopolitical programme of an extensive health care system
      could be developed which would have linked these three "pillars" in a sensible
      division of labour. On the one hand, original tasks of the public health system
      have been transferred to the private system of health care stressing the
      subsidiary of governmental action. On the other hand the public health service
      did not succeed in transforming the classical health care into a convincing
      system of local health service, which could fill the obvious gaps in the other
      parts of the health system. At present it is again under discussion whether
      public health service will play an original part in the system of health care,
      whether, following the principle of subsidiary it will only be assigned those
      tasks which nobody else will or can tackle or whether these will be complementary
      to those of the other sectors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7803949
TI  - [The Saxony public health service regulation].
AB  - Roughly only one year had passed after German reunification when the Saxon Health
      Service Law was enacted hat been conceived as the "constitution" of a public
      health service at a time when, ill-prepared, it faced the monumental task of
      bridging the gap between the gap between the public health structures of the
      former GDR and the legislation and experience of the Federal Republic of Germany.
      Essential aspects of the Public Health Law of the State of Saxony are: a) the
      fusion of both human and veterinary medical authorities into one ministry to
      enable the foundation of, amongst other things, an optimal organisational and
      structural basis for standardised care; b) the delegation of responsibility to
      the health department for the general health maintenance tasks of illness
      prevention, counselling and care of the population; c) special emphasis on
      environmental health protection measures, necessitated by the serious and hardy
      improved state of the environment. Uniform structuring and a minimum staff size
      are recommended for the Saxon health, food supervision and veterinary
      departments. Further legislation, statutes and guidelines that have since been
      passed are consistently assigning additional specific tasks and responsibilities
      to these departments.

PMID- 7803951
TI  - [Role of the public health (and environmental) office in urban development-
      current status and perspectives].
AB  - Our central question is how the local public health services can influence urban
      development and urban renewal policies. The need for a three-way cooperation
      between departments of urban planning and development, environmental affairs and
      health is now being widely acknowledged. In practice, however, it has to face
      manifold and serious problems. We suggest that there are basically three
      essential "instruments" which could lead to a new and defined role of health
      departments in urban development: environmental and health audits, local health
      profiles and "health promotion committees" or similar bodies for closer
      cooperation at the local level. These three "instruments" are described in terms
      of the present state of development and dissemination by analysing empirical
      studies from public health research. The results indicate that the "new role" of
      local health services in urban planning and development is presently fulfilled
      only in a few pilot cases. The lack of basic requirements particularly in terms
      of resources, motivation and qualifications is the main cause for the inability
      to implement the three "instruments" on a broader level in local health services.

PMID- 7803947
TI  - Effects of antidepressants on cognitive functioning of elderly patients. A
      review.
AB  - The influence of antidepressants on cognitive performance in elderly patients has
      been investigated in 18 studies. More than 70 different psychological tests or
      batteries of tests could be identified in these studies. The tentative
      conclusions that can be drawn are as follows. Monoamine oxidase (MAO) inhibitors
      hardly influence cognitive performance. Amitriptyline, dothiepin, mianserin and
      trazodone impair attention and ability to concentrate. Drugs with anticholinergic
      properties, such as nortriptyline, maprotiline and amitriptyline, might impair
      aspects of memory. For nortriptyline, higher plasma concentrations correlate with
      greater cognitive impairment. Cognitive impairment induced by nortriptyline
      during treatment might not be a transient effect, but may last as long as
      treatment continues. Data regarding the effects of selective serotonin (5
      hydroxytryptamine) reuptake inhibitors on cognitive performance in the elderly
      indicate no detrimental effect. A consensus on the use of instruments evaluating
      cognitive performance is needed to allow better comparison of future studies. As
      these conclusions can only be provisional, more study is needed.

PMID- 7803948
TI  - Vinorelbine. A review of its pharmacological properties and clinical use in
      cancer chemotherapy.
AB  - Vinorelbine is a semisynthetic vinca alkaloid with a broad spectrum of antitumour
      activity. The drug is effective as a single agent in inoperable/advanced non
      small cell lung cancer (NSCLC), producing objective response rates of about 15 to
      30%, and as first-line or later chemotherapy for metastatic spread in advanced
      breast cancer. Combining vinorelbine with standard chemotherapeutic regimens
      improves response rates in these indications compared with vinorelbine
      monotherapy: in NSCLC response rates increase to 30 to 50% when vinorelbine is
      administered with cisplatin. Importantly, survival was prolonged by a further 9
      weeks with this combination in a trial in > 600 patients with NSCLC. Comparative
      trials evaluating vinorelbine in women with advanced breast cancer are few at
      present. However, results suggest greater efficacy for vinorelbine than for
      melphalan as second-line chemotherapy, and similar efficacy for vinorelbine plus
      doxorubicin compared with doxorubicin plus 2 other drugs as first-line
      chemotherapy. Vinorelbine has tended to yield superior response rates when
      compared with vindesine, and appears to have greater haematological toxicity
      (i.e. granulocytopenia) but less neurological toxicity (peripheral neuropathy,
      constipation, loss of deep tendon reflexes) than this agent. Myelosuppression is
      the most frequent cause of vinorelbine treatment delay or dose reduction. Other
      consequences of vinorelbine therapy are those typically seen with antineoplastic
      agents, such as diarrhoea, nausea and vomiting, and alopecia. However, these are
      rarely severe. Early clinical investigations indicate that the antitumour effects
      of vinorelbine in other malignancies including ovarian carcinoma, lymphoma and
      head and neck cancer warrant further exploration, as does the efficacy of the
      drug relative to standard approaches and its possible beneficial effects on
      quality of life of cancer patients. Clarification is also required of the
      feasibility of an oral dosage form, which in preliminary investigations has shown
      some efficacy in NSCLC, but a variable response rate and high incidence of
      gastrointestinal disturbances in women with breast cancer. Thus, vinorelbine as a
      single agent or combined palliative therapy is effective against advanced NSCLC,
      and as first- or second-line chemotherapy in advanced breast cancer. This
      semisynthetic vinca alkaloid has a manageable tolerability profile and potential
      for use in other malignancies and as an oral formulation. With these attributes,
      vinorelbine is a valuable option which extends the range of treatments available
      for these difficult-to-treat malignancies.

PMID- 7803953
TI  - [Responsibilities and problems in national health reporting].
AB  - Complaints about the inadequate data situation in public health services are not
      new. However, during the course of the past few years there have been significant
      developments: the board of experts for concerted action in the public health
      services requested an improvement to the situation and the Federal Government
      promoted a preliminary study on the establishment of a national health reporting
      system (GBE) in Germany. Under the responsibility of the Federal Statistics
      Office, a national GBE is currently being established through further promotion
      by the Federal Ministry for Research and Technology (BMFT) and the Federal Health
      Ministry (BMG); the standard users of this system will be both the general public
      as well as the bodies responsible for health policy and scientific research. In
      the public health services there exist complete, but improveable data sources or
      incomplete sources requiring selection; also, new data sources must be won. In
      establishing the GBE, it is being assumed that public health services
      participants willing to cooperate already have at their disposal extensive data
      that does not need to be newly acquired, but does need improved mutual co
      ordination. The GBE can be established on this. Further supplementary data
      acquisition is only being considered for a later stage.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7803952
TI  - [Basic medical care of drug dependent patients and young homeless persons--a
      report from general practice].
AB  - During the last few years there has been an increasing number of reports from the
      staff in low level acceptance institutions as well as from streetworkers, about
      poor physical condition among drug addicts and young drifters. In May 1993 this
      caused the Public Health department of Cologne to set up a mobile medical
      service. This service offers consultation hours in so called "contact cafes" as
      well as in an out-of-service ambulance for drug addicts of the open drug scene
      and young drifters around the central station. Past experience has shown that the
      affections are by no means trivial ones. Phlegmoneous inflammations, abscesses,
      parasitosis and pyodermias of any kind as well as lesions of peripheral nerves
      and different kinds of acute or chronic virus infections are among the diseases.
      Without medical treatment there will be grave consequences. Difficulties in the
      treatment of drug addicts and other marginal social groups formed the term of the
      patient "who resists any medical treatment". As a result of bad experiences with
      existing medical institutions drug addicts consult the doctor either too late or
      they break off the treatment too early. In the treatment of drug addicts and
      young homeless it is absolutely necessary to face them without any prejudice and
      to create an atmosphere of confidence in order to guarantee an efficient medical
      care. There traditional medical services are not able to provide medical aid, the
      public health department is obliged to establish possibilities of complementary
      treatment. Drug addiction and homelessness cannot mean exclusion from medical
      care. That would also mean that the health insurances should participate in the
      costs.

PMID- 7803954
TI  - [Toward a European health reporting system--starting points and developmental
      perspectives].
AB  - This article first offers a brief introduction to the development of the EC
      health policy mandate from a competence restricted to health protection at the
      working place to a wider competence embracing health promotion and disease
      prevention, albeit still based on the principle of self-responsibility of the
      Member states. Possible focal points of health reporting within the EC framework
      are worked out on the basis of suggestions made by the EC commission in respect
      of priority areas of EC activities in the public health sphere and the
      commission's own priority criteria. It is then examined whether and to what
      extent the presently available health databases (especially of WHO and OECD)
      would cover these requirements. As a result, it is argued, that there is no
      getting around setting up an own health reporting system that would promote and
      support the development of an EC public health policy. An important task of such
      health reporting will be to supply users not only with data but also with
      adequate knowledge on how to interpret them, in view of the multitude of problems
      involved in bringing the various national health data under one roof; this cannot
      be achieved either at short notice or on a medium-term basis. Finally, a few
      alternatives are given in respect of possible organisational structures of EC
      health reporting, pointing out decision criteria and practical conditions which
      would be essential of assessing the usefulness of such organisational setups.

PMID- 7803955
TI  - [Preserving primary dentition until permanent teeth erupt].
AB  - International and regional trends in caries decline are described and a review of
      the efficacy of different caries preventive regimens in kindergarten children is
      given. It is concluded that in a situation of established oral hygiene in many
      kindergartens now the quality of this regimen has to be improved. Controversies
      about restorative materials used for deciduous teeth support the measures of
      caries prevention.

PMID- 7803956
TI  - [Diagnosis of caries risk within the scope of group prevention].
AB  - Dental epidemiological research in Germany has recently shown that the major part
      of caries affected teeth is only found in a small part of the population. This
      finding mainly refers to children and adolescents. Three quarters of all carious
      teeth for instance are found in one third of children aged 8 to 9 years. This
      fact requires intensified preventive proceedings for children with an apparently
      increased caries risk. Caries preventive steps, however, can only be effective if
      the identification of children with increased risk takes place before the first
      carious damage has occurred. Actually, there is no method to solve this problem
      in an optimal way. Under this restriction the Dentoprog-method which has been
      developed at the University of Zurich is considered the best solution for school-
      based steps in caries prevention.

PMID- 7803957
TI  - [Adaptation of medical care to the changing disease spectrum of adolescents].
AB  - The spectrum of diseases affecting today's children and adolescents has changed.
      Today's urgent health problems are no longer acute and infectious disorders but
      much rather psychosomatic and chronic disorders. However, the present health
      delivery system has not adapted its structure to this changed spectrum of
      disease. This paper reports on a study carried out by the project "Health Risks
      and Structures of Medical and Mental Health Care." The project belongs to the
      North Rhine-Westphalian Consortium for Public Health, and the study was carried
      out in cooperation with the Special Research Unit 227: "Prevention and
      Intervention in Childhood and Adolescence." Results show that a small proportion
      of adolescents actually consult general practitioners. Inadequate cooperation
      between medical and mental health care services as well as insufficient links
      between these services and the life world of adolescents have led to a situation
      in which the use of professional assistance meets with barriers. As a result,
      adolescents continue to avoid visiting a physician even when they have already
      become ill. For this reason, there is an increasingly strong need to consider how
      to change the structures of medical and mental health care. Proposals are
      developed that meet the needs of adolescents and are oriented toward the
      requirements arising from the changing spectrum of disease.

PMID- 7803958
TI  - [The violent patient and institutional counter-violence].
AB  - The treatment of violent patients confronts the individual psychiatric
      professional as well as the psychiatric institution as a whole with a difficult
      therapeutic task. In order to cope with frightening interactions an
      "institutionalized system of defense" (Mentzos) is needed to protect the
      individual staff member. Under unfavourable institutional circumstances the
      defence manifests itself as counter-aggression. The mutual reinforcement of
      patient-aggression and institutional counter-aggression is not at all specific
      for custodial psychiatry. Reformed institutions with a liberal attitude may
      develop subtle manifestations of counter-aggression to protect the professional
      identity of their members. The aim to maintain a "good", non-violent psychiatry
      proves to be an obstacle to any effort to cope with the needs of the violent
      patient and to reduce institutional counter-aggression to a minimum.

PMID- 7803959
TI  - [Are there predictors for impulsive, homicidal-suicidal acts of violence].
AB  - Patient's statements or fears that they may "go crazy" and harm themselves or
      persons around them are rare, but extremely difficult for all participants to
      deal with. On the basis of the existing, unsatisfactory literature as well as an
      analysis of 196 incidents of homicidal-suicidal violence designated by German
      media as "running amok" and fulfilling defined criteria, we examined whether or
      not there are predictors for the degree of potential danger inherent in such
      threats. Impulsive, homicidal-suicidal acts of violence among patients with
      psychiatric disorders often occur in environments characterised by chronic
      psychosocial estrangement and isolation. Extremely distressing situations may
      trigger the course of violence, but the actual act is often planned during a
      seemingly peaceful interval. Personalities with a high affinity to weapons and a
      tendency toward acting out seem to increase the potential risks. Such events
      should be treated analogous to suicidal crises, with a strategy that takes the
      individual disorder into consideration. The parameters investigated in this paper
      are not sufficient, even in different combinations, to offer a satisfactory
      explanation or predict the occurrence of this extremely rare behaviour; further
      research is necessary.

PMID- 7803960
TI  - [Sexually abused children in public health services].
AB  - Referring to case examples it is shown how staff in local health services get
      into contact with sexually abused children. The responsibility of the
      "Gesundheitsamt" is shown regarding. 1. the organisation of professional help in
      individual cases 2. the organisation of institutional cooperation to provide
      professional help in the community.

PMID- 7803961
TI  - [Human biomonitoring after a severe chemical accident--results of a study after
      the Hoechst AG chemical spill 22 February 1993].
AB  - A major industrial chemical accident occurred on 22 February 1993 at Hoechst AG
      Frankfurt/Germany. Approximately 11.8 tons of a chemical mixture (mostly
      chlorinated nitroarenes) were emitted, resulting in heavy contamination of
      Schwanheim, a nearby housing area. Urine samples were collected from the
      inhabitants of the affected area a few days after the accident and were analyzed
      for o-nitrophenol (ONP) as a representative metabolite to assess the actual
      uptake of the pollutants. As a result, ONP was found in urines of control
      subjects from elsewhere, an observation hitherto not described in the literature.
      Mean ONP excretion was about three times higher in the Schwanheim population than
      in the controls. The results show not only a higher accident-related but also a
      higher permanent ONP-excretion of the population of Schwanheim, pointing to a
      permanent environmental pollution in Schwanheim. Both results, the hitherto
      unknown ONP excretion in controls and regional differences in ONP excretion,
      require further investigation.

PMID- 7803962
TI  - [Incidence of lichens in the area of the Hamburg airport].
AB  - It was examined whether the co-additional effect of kerosene and benzine
      influences the air quality and the population of lichens. These plants were
      chosen since lichens serve as important indicators of air pollution. It was found
      that exhaust gases from a much frequented highway influence the number and the
      variation of species of lichens, whereas near the runway some less common species
      were found. These results show that air traffic exercises less influence on the
      lichen population than the road traffic emissions.

PMID- 7803963
TI  - [Refuse incinerators in industrial areas (pro and contra)].
AB  - Update refuse incineration plant is meanwhile available as complete residue
      utilisation and recycling plant at reasonable waste disposal cost. Residual
      refuse of unknown composition is transformed into defined raw materials. The
      resulting "products" of such high-temperature treatment plant are energy, glass
      slake, gypsum, hydrochloric acid and metal fractions that can be re-introduced,
      i.e. recycled, into the cyclic process applicable to raw and engineering
      materials.

PMID- 7803964
TI  - Who does what in critical care?

PMID- 7803965
TI  - Nutrition of critically ill people.
AB  - There has been an increasing awareness over the past few years of malnourishment
      in hospital patients (Horwood 1990, Wallace 1993). Critically ill patients are a
      particularly vulnerable group as their physical problems can mean depleted energy
      reserves and an increase in energy consumption. The aim here is to consider ways
      in which malnutrition can be avoided in critically ill people. Different methods
      to provide patients with adequate nutrition, and the associated complications,
      are also discussed. To give critically ill patients the best possible chance of
      survival, intensive care staff need to be aware of recent developments in
      clinical nutrition. A multidisciplinary approach to nutrition is essential to
      achieve the best possible outcome for patients in intensive care units (ICUs).

PMID- 7803966
TI  - Effect of level of lung injury on HR, MAP and SaO2 changes during suctioning.
AB  - 25 patients with documented lung injury were suctioned using a manual
      resuscitation bag (MRB) and a standardised procedure. Level of lung injury was
      not significantly correlated with changes from baseline in heart rate (HR) oxygen
      saturation (SaO2) or mean arterial pressure (MAP). However, HR and MAP increased
      significantly returning to baseline at 5 min. Patients' SaO2 did not change
      significantly during the procedure or up to 15 min afterwards. No changes in
      cardiac rhythm were found during the event or for 15 min afterwards. Standards
      for hyperoxygenation and hyperinflation could not be achieved using the MRB even
      with a standardised procedure.

PMID- 7803967
TI  - Transport systems for the critically ill: focuses for development.
AB  - There is a worldwide increase in the transportation of critically ill patient
      which reflects the increasing technological specialisation and centralisation of
      services. In the United Kingdom (UK) a minimum of 10,000 patients with life
      threatening illnesses are transported between hospitals each year (Wright,
      McDonald & Rogers 1988). Transport programmes are generally being more carefully
      assessed, and application of past experience can make them safer for patients and
      personnel and most cost-effective (Purdie, Ridley & Wallace 1990). This applies
      to both primary (movement of a patient from the community to hospital) and
      secondary transport (movement of a patient between hospitals). These processes
      are as active in the UK as in other countries with developed systems of medical
      care. This paper will focus on two important areas, which are relevant to how
      transport facilities may be expanded for the best overall advantage. These areas
      are the means of transport and the transporting team. The discussion is supported
      by a literature review. It became apparent on preparing this paper that much of
      the transport literature from other countries, whilst helpful, is not directly
      applicable to the UK.

PMID- 7803968
TI  - Understanding the pre-operative information needs of patients and their relatives
      in intensive care units.
AB  - A descriptive study was undertaken to assess the pre-operative information needs
      of patients and relatives admitted electively to intensive care units (ICU)
      following surgery. A convenience sample of five patient and relative groups were
      interviewed pre- and postoperatively. The interviews were analysed using thematic
      content analysis (Burnard 1991). The findings showed that the patient and
      relative dyads' 'expressed worries' related to the anaesthetic, surgery and ICU;
      patients stated that their relatives were more anxious than they were. The
      findings are similar to the pre-operative 'information needs' in which patient
      and relative dyads sought information regarding the surgery, visiting and
      treatment regimes in ICU. The most important information need identified was 'the
      need to understand the operation'. From the findings it was concluded that the
      nature of the information sought by ICU patients and their relatives was
      associated with perceived harms and threats related to the hospitalisation.
      Information which was structured to meet individual needs reduced anxiety and
      increased satisfaction with the information provided.

PMID- 7803969
TI  - Ventricular septal defects. A case study and discussion.
AB  - Ventricular septal rupture is a serious complication of acute myocardial
      infarction (MI) that generally produces progressive circulatory failure and rapid
      deterioration. Prompt diagnosis followed by surgical repair with peri-operative
      circulatory support is often life-saving (Mazeika et al 1994). The following is
      an account of a patient that I cared for, whilst working on the coronary care
      unit (CCU) as part of an ENB 125 course. The patient was originally admitted with
      an inferior MI and went on to develop a ventricular septal defect (VSD).

PMID- 7803970
TI  - Meningococcal meningitis.

PMID- 7803971
TI  - Hallucinations following cardiac surgery in a paediatric intensive care unit.
AB  - Abnormal behaviour as a result of benzodiezapine withdrawal has been reported in
      children in intensive care. Other causes of abnormal behaviour may be as a result
      of intensive care unit (ICU) psychosis or delirium. ICU psychosis in adults is
      well documented but is rarely reported in children, hence this report on a child
      who suffered hallucinations after cardiac surgery, and discussion on possible
      causes and the need for greater awareness of this possible complication.

PMID- 7803972
TI  - Philosophy and models in critical care nursing.
AB  - In 1991 a new philosophy and nursing model was developed in the adult intensive
      care unit. A team approach over several months, through the exploration of
      attitudes, values and beliefs, gave rise to the unit philosophy. The philosophy
      identified the beliefs of the nursing team which then, along with identified
      knowledge and goals for practice, directed us towards an appropriate nursing
      model. The Mead model, an adaptation from Roper, Logan & Tierney's model, was
      chosen and then adapted further. We believe the resulting model, although not
      perfect, guides our practice, reflects our beliefs, and is practical and 'user
      friendly'.

PMID- 7803973
TI  - A salutary lesson.
AB  - When a group of nurses decided to improve facilities for patient's relatives they
      did not anticipate the unusual series of events described here. Fortunately the
      outcome was extremely satisfactory. It could, however, have been quite different,
      and served to heighten nurses' awareness of the potential impact that they may
      have on relatives.

PMID- 7803974
TI  - Nurses' attitudes to visiting in coronary care units.
AB  - In many coronary care areas there are still restricted visiting times (Shaw
      1989). This investigative study describes some relevant research in this area,
      and documents a small study of 14 nurses in two coronary care units (CCUs). A
      semi-structured interview was used to obtain information regarding nurses'
      attitudes to visiting. The results showed that the majority of these nurses are
      flexible when it comes to visiting, and expressed a relaxed attitude to it.
      Although in the area investigated visiting times are specified, some nurses
      consider and act on the concept of individualised patient care. However, there
      are still some nurses who insist on doing everything for the patient in the
      morning and only allow relatives access in the afternoon. These nurses also
      believe visiting times are precious to the patients and relatives and will not
      intrude on them, which may limit communication.

PMID- 7803975
TI  - Fever: friend or foe?
AB  - Fever is one of the most common manifestations of disease. The patient's
      relatives and physicians' concern about it is due to the fact that fever reflects
      that something in the body is not working well. However, the question on fever as
      convenient or harmful is not yet completely answered. The purpose of this paper
      is to examine the arguments on both sides and to guide on the convenience of
      antipyretic treatment.

PMID- 7803976
TI  - From circadians of the fifties to chronomes in vitro as in vivo.
AB  - In a recent review of cellular mechanisms of entrainment, an ocular circadian
      rhythm of Bulla was reported (1). The isolated retina of this marine mollusk is
      described to contain a circadian oscillator. A glance at the spontaneous impulse
      frequency from eyes recorded in darkness at 15 degrees C suggests lower-frequency
      modulations of the about 24-h rhythm and prompts the quantitative assessment of
      the broader time structure, the chronome, in this extensively used model of a
      budding neurochronophysiology. The cultured retina of mollusks is interpreted by
      the original authors as descriptive of similar cellular mechanisms that may
      underlie mammalian as well as molluscan physiology. We report here the
      rhythmometric analysis of the original data by Block et al. (2), taken from
      Figure 2 of the article by Colwell et al. (1), resolved by computer just as the
      microscope resolves cellular structure. The results are further compared with
      those obtained on data kindly provided by Stephan Michel on another retina of
      Bulla. The findings of multiple chronome components (beyond the circadian system)
      are placed into the broader context of cell biophysics and its implications for
      biomedicine within the scope of an international chronome endeavor.

PMID- 7803977
TI  - Intestinal amebiasis: histopathologic features in experimentally infected mice.
AB  - Intestinal amebiasis is still an important health problem in developing regions
      of the world. In order to advance our knowledge on the pathogenesis and to test
      the relevance of recently obtained in vitro observations, suitable in vivo
      experimental models of intestinal amebiasis are needed. In the past a variety of
      laboratory animals have been used, but the mouse, whose genetics and immunology
      is well known, has been seldomly used. Therefore, Entamoeba histolytica strain
      HM1:IMSS was directly inoculated into the cecum of C3H/HeJ mice, which were
      sacrificed at 5, 10, 15, 20, 25 and 30 days for histopathologic analysis. An
      ulcerative inflammatory disease highly reminiscent of human amebiasis was
      observed. Early 5 day lesions consisted of tiny erosions of the surface
      epithelium which evolved to deeper and more extensive destructive lesions of the
      cecal wall. Indeed, flask-shaped ulcers, intestinal perforations and intramural
      abscess formation were observed at later times. It was noticeable that, despite
      the lack of obvious significant tissue invasion by amebae, ulcerative disease was
      extensive and found virtually in all mice. These observations support the view
      that tissue invasion by trophozoites is not necessarily required for ulcerative
      disease to occur, suggesting a role for toxic factors released by amebae.

PMID- 7803978
TI  - Frequency of enterotoxigenic Escherichia coli in infants during the first three
      months of life.
AB  - To know at what age infants begin to excrete enterotoxigenic Escherichia coli
      from feces, we studied 30 infants belonging to low socioeconomic status during
      the first 3 months of life, taking 11 samples of feces from each infant,
      beginning at the day of birth. We detected LT and ST enterotoxins of E. coli
      using ELISA test. From the samples studied, 34 samples from 21 (70%) infants were
      positive for LT. In four samples (1.2%), the presence of LT-producing E. coli
      coincided with diarrhea, corresponding to three (10.0%) from the infants studied.
      The earliest age that we observed LT-producing E. coli was day 0 (day of birth).
      We did not find ST + or LT/ST-producing E. coli strains. We concluded that ETEC
      strains are frequent findings in healthy infants, and its presence is too early
      in persons of low socioeconomic status.

PMID- 7803979
TI  - Estrogenic actions of norethisterone and its A-ring reduced metabolites.
      Induction of in vitro uterine sensitivity to serotonin.
AB  - The estrogen-like effects of norethisterone (NET) seem to be mediated by the
      interaction of 3 beta 5 alpha- and 3 alpha 5 alpha-tetrahydronorethisterone (3
      beta 5 alpha- and 3 alpha 5 alpha-NET, respectively) with the estrogen receptor.
      Considering that the in vitro uterine contractile response to serotonin (5-HT) is
      specifically dependent on estrogen, the aim of the present study was to
      investigate whether NET and its A-ring reduced metabolites administered in vivo
      to ovariectomized rats induce uterine sensitivity to 5-HT in vitro. The
      administration of 3 beta NET in vivo, which is the NET metabolite with the
      highest affinity for the estrogen receptor, induced a maximal contractile
      response to serotonin similar to that of 17 beta-estradiol treatment. The other
      metabolites induced less uterine activity. According to the effective dose 50,
      the order of estrogenic potency was 17 beta-estradiol > 3 beta 5 alpha NET > 3
      alpha 5 alpha NET > NET > 5 alpha NET. The estrogenic effect of 3 beta 5 alpha-
      and 3 alpha 5 alpha NET may be exerted through their interaction with the
      estrogen receptor, whereas NET and 5 alpha NET, which do not bind to the estrogen
      receptor and display a minor estrogenic activity, require prior bioconversion to
      3 beta 5 alpha NET and perhaps to 3 alpha 5 alpha NET. The A-ring reduced
      metabolites of NET, mainly the 3 beta 5 alpha NET, may be exerting estrogenic
      responses and modulating uterine activity when administered in vivo.

PMID- 7803980
TI  - Etiological review of hirsutism in 250 patients.
AB  - Two hundred fifty women with hirsutism were studied, with a mean age of 25.5
      years (ranging from 13 to 38 years). The evolution of hirsutism varied from 3
      months to 13 years, being minimal in 82 patients (33%), mild to 101 (40%),
      moderate in 56 (23%) and severe in the remaining 11 women (4%). Polycystic ovary
      syndrome (PCOS) was diagnosed in 134 patients (53%), overweight or obesity in 45
      (18%), late-onset adrenal hyperplasia in five (2%), ovarian tumor in two (0.8%),
      drug-induced hirsutism and Cushing's syndrome in one patient each (0.4%), and
      idiopathic hirsutism in 62 cases (25%). Among 67 patients with moderate or severe
      hirsutism, testosterone was elevated in 21 (31%). In 117 out of 206 (57%) cases
      polycystic ovaries were observed by ultrasound. Fifty-four patients were treated
      with a combination of 2 mg cyproterone acetate and 0.035 mg ethinyl estradiol,
      observing improvement of hirsutism in 32 patients (59%). It is concluded that
      PCOS is the most frequent cause of hirsutism, but an important proportion of
      cases without evident etiology remain classified as idiopathic hirsutism.

PMID- 7803981
TI  - Heterogeneity of late-onset adrenal 3 beta-ol-hydroxysteroid dehydrogenase
      deficiency in patients with hirsutism and polycystic ovaries.
AB  - Nine women with clinical features of polycystic ovarian syndrome (PCOS) were
      studied in order to establish the differential diagnosis with late-onset adrenal
      hyperplasia (LOAH). Their hirsutism was classified as moderate in five patients
      and severe in the remaining four cases. All patients had bilateral polycystic
      ovarian enlargement by ultrasound examination. As a control group five women with
      normal ovarian function without hirsutism were submitted to the same protocol of
      study. The patients studied as well as the women of the control group had basal
      serum determinations of pregnenolone (P5),17-hydroxypregnenolone (17
      OHP5),dehydroepiandrosterone (DHEA), pregesterone (P), 17-hydroxyprogesterone (17
      OHP), androstenedione (A), testosterone and cortisol by radioimmunoassay
      techniques. The basal serum levels of androgens showed no correlation with the
      severity of hirsutism or with the ultrasound findings. An adrenal stimulation
      with synthetic adrenocorticotropic hormone (ACTH) to all women was performed in
      order to assess their adrenal responsiveness. The analysis of the ratios between
      delta 5 and delta 4 steroids demonstrated a partial enzymatic blockade at the
      level of 3 beta-o1-hydroxysteroid dehydrogenase (3-HSD) in three patients. The
      blockade was particularly in the conversion of P5 to P and 17-OHP5 to 17-OHP. The
      lack of delta 4 steroid secretion in the presence of normal increase of delta 5
      precursors following ACTH was noted. These findings confirm the clinical use of
      the ACTH stimulation test to reveal the presence of enzymatic alterations in
      adrenal steroidogenesis in some patients previously considered to have PCOS.
      Since it wa demonstrated that the conversion steps were affected in variable
      degrees, the presence of different isoenzymes of 3-HD is suggested.

PMID- 7803982
TI  - Comparative analysis of plasmids from nosocomial Klebsiella pneumoniae strains
      isolated from two hospitals.
AB  - A total of 46 clinical isolates of Klebsiella pneumoniae were studied. Of these,
      33 were from "Hospital Infantil de Mexico" (HIM) and 13 from "Hospital General de
      Mexico" (HGM). The susceptibility of these strains to five antibiotics, as well
      as the plasmid DNA profiles, were determined for each group. Antibiotic
      susceptibility profiles were very similar in strains from both hospitals;
      however, most of the strains analyzed exhibited heterogeneous plasmid DNA
      profiles. Results showed that strains isolated in the two hospitals did not
      differ regarding morphology, biochemical profiles, antibiotic susceptibility or
      plasmid populations, and these characteristics may not be used as markers to
      differentiate Klebsiella pneumoniae strains from different hospitals.

PMID- 7803983
TI  - Protein uptake by cysticerci of Taenia crassiceps.
AB  - The internalization of host macromolecules to the vesicular fluid of T.
      crassiceps cysticerci was studied in vitro. Uptake of purified class G
      immunoglobulin was not significantly affected by the specificity of its antigen
      recognition site and bovine serum albumin was internalized at a similar rate.
      Internalization was inhibited at low temperature, being optimal at 37 degrees C
      and saturation was accomplished only at a protein concentration in the culture
      medium over 12 mg/ml which is close to the physiological concentration of serum
      proteins in the host. Morphological studies using markers for adsorptive
      endocytosis allowed visualization of endocytic vesicles and tracking of their
      movement across the bladder wall tissue. Degradation of internalized proteins was
      observed at longer times of incubation, suggesting that proteins are later
      processed and that degraded host macromolecules can be nutrients for cysticerci.
      Quantification of this capability of internalization suggests that it might play
      a role in the in vivo removal of potentially damaging host macromolecules, such
      as antibodies or complement factors, from the host-parasite interface.

PMID- 7803984
TI  - Characterization of a fluorometric method for lipoprotein lipase.
AB  - A fluorometric assay for determining lipoprotein lipase (LPL) activity is
      described. Dibutyrilfluorescine (DBF) was used as substrate for the enzyme and
      the fluoresceine liberated by enzymatic hydrolysis of the substrate was measured.
      Extracts of acetone powder from adipose tissue as an enzyme source showed
      characteristics of lipoprotein lipase activity, i.e., inhibition by NaCl and
      optimum activity in alkaline pH. There was close agreement in LPL activity when
      the same sample was measured simultaneously using either dibutyrilfluorescine or
      tri[9,10(3)H]oleylglycerol as substrate. The extent of inhibition of lipoprotein
      lipase by NaCl was similar with both methods. The fluorometric method detected
      changes in LPL activity in heart and adipose tissue related to the nutritional
      status of the animal with the same specificity and sensitivity than did the
      radioactive method. The fluorometric method is as sensitive, less expensive and
      less time consuming than the radioactive method.

PMID- 7803985
TI  - Hypothalamic monoamine oxidase activity in ovariectomized rats after sexual
      behavior restoration.
AB  - The effect of estradiol benzoate, progesterone and a sequential treatment with
      both on the activity of the enzyme monoamine-oxidase (MAO) was assessed in
      mitochondria from hypothalami of ovariectomized rats. A differential effect on
      the subtypes A and B MAO was found according to the type of treatment. Estradiol
      benzoate administration decreased MAO activity, mainly that of MAO-A.
      Progesterone alone had no effect, and sequential treatment with estradiol
      benzoate plus progesterone restored sexual behavior and produced a significant
      increase of MAO-A activity, without changes in total MAO activity. Since MAO-A is
      an isoform of MAO that preferentially uses norepinephrine and serotonin as
      substrates and MAO-B acts on phenylethylamine and benzylamine as substrates, our
      findings suggest that the restoration of sexual behavior after the treatment with
      estradiol benzoate followed by progesterone may be associated with the
      differential effect exerted by the hormones on MAO subtypes, rather than to the
      simple decrease in hypothalamic monoamine concentrations as reported in the
      literature.

PMID- 7803986
TI  - Effect of systemic monosodium L-glutamate on muscarinic cholinergic receptors in
      selected rat brain regions during development.
AB  - [3H]quinuclidinyl benzilate ([3H]QNB) binding to muscarine acetylcholine
      receptors (mAchR) was measured in cerebral cortex and caudate nucleus of rats at
      the ages of 7, 14, and 21 days, which had received a subconvulsive
      intraperitoneal dose of monosodium L-glutamate (MSG) (4 mg/g) on postnatal days
      1, 3, 5 and 7. MSG treatment determined an increase of mAchR density in cerebral
      cortex. This was 8, 15 and 25% at days 7, 14 and 21, respectively. In caudate
      nucleus, a significant increase of mAchR density was detected at day 7 (240%).
      However, on postnatal day 14, mAchR binding in caudate nucleus of MSG-treated
      rats was only 47% higher, while at 21 days, no changes in mAchR binding were
      found. When MSG was injected to adult rats, no changes in brain mAchR density
      were detected. Data suggest that early administration of MSG affects the
      development of mAchR in cerebral cortex and caudate nucleus, whereas the adult
      brain cortical cholinergic transmission is not sensitive to parenterally
      administered MSG.

PMID- 7803987
TI  - Prevalence and detection of hypertension in Mexico.
AB  - The aim of this study was to characterize the prevalence and detection of
      systemic hypertension in a low income urban area of Mexico City. The population
      of the studied area was 15,532 inhabitants, of whom 3505 (22.6%) were eligible
      for study (men aged 35-64 years and non-pregnant women). Home interviews were
      obtained on 2810 (80.2%) and physical and laboratory examination was performed on
      2282 individuals (941 men, 1341 women, 81.2% of those interviewed and 65.1% of
      all the eligibles). Blood pressure (BP) was measured using a random zero
      sphygmomanometer (Hawksley, London). Three measurements were made on the right
      arm after a 5 min rest, with the patient seated. The average of the last two
      determinations was taken as the patient's BP. High blood pressure (HBP) was
      defined as systolic BP > or = 160 and/or diastolic BP > or = 95 mmHg, or if the
      patient was taking antihypertensive therapy regardless of the blood pressure
      value. A total of 216 subjects (77 men, 139 women) met criteria for HBP. In the
      35-44 age group, prevalence for men was 4.16% and for women 3.06%. In the 44-55
      age groups the prevalence for men was 7.81% and for women 12.55%. In the 55-64
      year group the prevalence for men was 16.51% and for women 22.2%. Obesity was
      associated with HBP (body mass index in men with HBP was 28.9 kg/m2 vs. without
      26.9 kg/m2, p < 0.001; women with HBP, 30.8 kg/m2 vs. without 28.5 kg/m2, p <
      0.001.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7803988
TI  - Diabetic retinopathy in Mexico. Prevalence and clinical characteristics.
AB  - We present the results of a population based study designed to estimate the
      prevalence of diabetic retinopathy in a series of 284 type 2 diabetics residing
      in low income areas of Mexico City. These patients were identified in a survey
      performed between February 1990 and October 1992 (The Mexico City Diabetes
      Study). We located 214 (75.35%) of the original 284 patients and invited them to
      attend a clinic where they were interviewed and had a complete ophthalmologic
      examination. All participants had, in addition to the retinal examination by a
      certified ophthalmologist, seven fields stereo fundus photographs taken with a
      Topcon 50X retinal camera. Photos were taken using ASA 100 Kodak film and
      processed in their laboratory. All photographs were read and graded for quality
      and level of diabetic retinopathy (DR) in the Reading Center of the Department of
      Ophthalmology of the University of Wisconsin. A total of 37 (43.5%) men and 69
      (53.5%) women had no evidence of DR. In 16 (18.8%) men and 21 (16.3%) women there
      was background DR. In 25 (29.4%) men and 30 (23.3%) women there was
      preproliferative DR. In 5 (5.9%) men and in 7 (5.4%) women there was
      proliferative DR. Macular edema was diagnosed in 7 (8.2%) men and 6 (4.7%) women,
      of these in 3 (3.5%) men and in 5 (3.9%) women the macular edema was central.
      This complication is associated with duration of diabetes, chronic poor metabolic
      control and microalbuminuria. A very significant proportion of cases with sight
      threatening DR remains undiagnosed and untreated. Consequently there is a
      significant number of cases developing into blindness that could have been
      prevented.

PMID- 7803989
TI  - [Aluminum contaminated infusion solutions: a little appreciated iatrogenic health
      risk in intensive care medicine].

PMID- 7803991
TI  - Parenteral aluminum loading in critical care medicine. Part II: Response to
      aluminum load from long-term parenteral nutrition.
AB  - OBJECTIVE: Evaluation of the iatrogenic aluminum load by aluminum-contaminated
      nutritive infusion solutions in long-term total parenteral nutrition (TPN).
      PATIENTS: 16 consecutive patients (6 children, 10 adults) who had to undergo
      total parenteral nutrition for more than one month. Three of them were from a
      home parenteral nutrition program. The duration of TPN was up to 68 months. The
      parenteral aluminum load was calculated on the basis of the individual TPN
      programs. Six patients were exposed to an additional parenteral aluminum load in
      the course of intensive care. Comparative group: To establish a reference range,
      the serum aluminum concentrations were determined in 71 unloaded patients who had
      to undergo minor surgical procedures. ALUMINUM ANALYSIS: Strict adherence to a
      contamination-free sampling and processing technique. The aluminum determination
      was performed at the Hahn-Meitner-Institute Berlin by means of graphite-furnace
      atomic absorption spectrometry (GFAAS). RESULTS: The TPN-associated daily
      aluminum load was 3.5 +/- 0.4 micrograms/kg body weight (bw) in children and 2.2
      +/- 1.8 micrograms/kg bw in adults. 59 +/- 6% of the intravenous aluminum load in
      children and 42 +/- 16% in adults was due to the highly contaminated small-volume
      calcium, inorganic phosphate, trace element and vitamin parenterals. The median
      serum aluminum concentration under TPN was 10.9 micrograms/l (range: 5.0-26.9
      micrograms/l) and was thus 7.3 times higher than in the preoperative control
      group (median: 1.5 micrograms/l, 95% confidence interval: < 0.6-3.5
      micrograms/l). Individual values ranged up to 36.8 micrograms/l. CONCLUSIONS: The
      aluminum intake of patients on parenteral nutrition in Germany is thus on
      occasion considerably above the ASCN/ASPEN recommendations for the limitation of
      intravenous aluminum loading (ASCN: American Society for Clinical Nutrition;
      ASPEN: American Society for Parenteral and Enteral Nutrition). The toxicological
      significance of parenteral aluminum loading is discussed. The results suggest
      that limits should be established for the Aluminum contamination of infusion
      solutions.

PMID- 7803990
TI  - [Risk of transmission of HIV by blood products].

PMID- 7803992
TI  - Industrially manufactured all-in-one solution in visceral surgery.
AB  - OBJECTIVE: The goal of this study was to examine the handling and the effect of a
      commercially manufactured nutritional solution (VacuKit zero 1) on the
      postoperative metabolism and the liquid requirement after gastro-intestinal
      surgery. DESIGN: Open, prospective, nonrandomized study. SETTING: Ward of the
      visceral surgical department of a town hospital in Switzerland. PATIENTS: 36
      consecutive patients after gastro-intestinal surgery. INTERVENTIONS: During the
      first 5 postoperative days 2,000 ml of the commercially manufactured nutritional
      solution were administered daily; it was composed of amino acids (100 g), glucose
      (1,120 kcal), fat (820 kcal) and electrolytes. RESULTS: The nitrogen balance in
      the postoperative phase was always positive. Laboratory analysis shows that this
      nutrition solution is well accepted, with stable carbohydrate and fat metabolism
      and with normal liver and electrolyte parameters. The patients received an
      average of 500 ml/24 h of additional liquids. CONCLUSIONS: Administration and
      handling of the solution VacuKit zero 1 requires no special equipment. The
      nutritional solution proved to be a safe and simple method of parenteral
      nutrition for metabolically stable patients in the visceral surgery department.

PMID- 7803993
TI  - Effect of two lipid emulsions on platelet function.
AB  - OBJECTIVE: To examine the effect of two lipid emulsions administered with total
      parenteral nutrition (TPN) on platelet aggregation and activation and the
      production of eicosanoids in nonseptic critically ill patients. DESIGN:
      Prospective, randomized, unblinded, non-crossover study. SETTING: ICU of a
      general teaching hospital. PATIENTS: 23 adult, critically ill, nonseptic
      patients, who were in need of TPN for at least 7 days. INTERVENTIONS: The
      patients were randomly distributed into 2 groups each of which received TPN with
      a different essential fatty acid content. The 2 lipid emulsions, Intralipid 20%
      (long-chain triglycerides) and Lipofundin MCT/LCT 20% (10% each of long- and
      medium-chain triglycerides) provided 43% of the nonprotein caloric requirements
      calculated for each patient. Parameters demonstrating platelet function (plasma
      beta-thromboglobulin, platelet factor 4, platelet aggregation, 6-keto-PGF1 alpha)
      were assessed before starting TPN and after 4 and 7 days of initiation. RESULTS:
      Before beginning lipid perfusion, platelet activation evaluated by beta TG and
      PF4 levels was notable, 6-keto-PGF1 alpha production was elevated and no
      hyperaggregation of platelets was observed in patients. The studies of platelet
      function at 4 and 7 days of TPN did not show significant changes with respect to
      the basal data or between the 2 groups. CONCLUSIONS: Our results indicate that
      platelet function was not affected by either of the 2 lipid emulsions
      administered to patients during the study period.

PMID- 7803994
TI  - Kinetics of extracellular potassium concentration in irradiated red blood cells.
AB  - BACKGROUND: Irradiation of cellular blood components prevents onset of
      transfusion-associated graft-versus-host disease. The present study was designed
      to monitor the post-irradiation changes of the extracellular potassium
      concentration in red blood cells (RBC) stored in SAG-M (saline adenine glucose
      mannitol), in order to estimate the right time for their prophylactic irradiation
      and the right span of post-irradiation storage. MATERIALS AND METHODS: Ten units
      each of fresh, 10 days and more than 20 days stored SAG-M RBCs were divided into
      2 equal portions each. One portion was gamma-irradiated with 30 Gy (137Cs
      source). Another 10 fresh RBC units were separated, and portions were irradiated
      with 15, 30, 60 or 120 Gy. The determination of potassium was performed
      simultaneously in corresponding irradiated and non-irradiated portions;
      immediately after irradiation, after 1 and 5 days, and every 10 days of
      additional storage (up to 30 days). All measurements were performed in the cell
      free supernatant, using flame emission photometry. RESULTS: The extracellular
      potassium concentration increased permanently with the duration of storage both
      in non-irradiated and irradiated specimens. At the end of the period of storage
      this increase in the irradiated portions was approximately 2 times the potassium
      concentration of the non-irradiated portions (60 mmol/l vs. 38 mmol/l, p <
      0.001). Thereby no significant differences of the potassium efflux rates were
      estimated at the end of the period of storage between fresh RBCs irradiated and
      stored RBCs irradiated. The mean 5 days post-irradiation potassium release from
      fresh RBC units was similar to that in 25-30 days stored non-irradiated portions
      (34.3 mmol/l vs. 38 mmol/l). The extracellular potassium increase was irradiation
      dose-dependent (r = 0.89, p < 0.001). CONCLUSIONS: SAG-M RBCs can be irradiated
      with 30 Gy immediately post-harvest and subsequently stored for a couple of days
      prior to transfusion without producing critically high extracellular potassium
      concentrations.

PMID- 7803995
TI  - Identification of antibodies toward private and public class I HLA epitopes in
      sensitized patients.
AB  - BACKGROUND: Antibodies to HLA determinants may decrease the increment after
      platelet transfusion and are correlated with increased rates of rejection in
      renal transplantation. Cross-match tests and HLA antibody specification are used
      to identify compatible donors for sensitized patients. However, search for cross
      match negative donors may be ineffective, and many sera containing antibodies
      toward public HLA epitopes give no clear results in conventional specificity
      analysis. MATERIALS AND METHODS: We tested a series of 4,625 sera from 1,073
      patients with hematological, malignant or other diseases using a fluorescence
      lymphocytotoxicity test (LCT). We applied an evaluation program incorporating a
      list of public antigens belonging to known cross-reacting groups (CREGs) to
      detect antibodies toward private and just as well public epitopes. RESULTS: In
      694 sera (15.0%) from 240 patients the panel reactivity (PRA) in LCT assay was
      higher than 5%. PRA was > or = 50% in 258 (37.2%) and < 50% in 436 sera (62.8%).
      In both groups we identified specific antibodies toward public HLA class I
      epitopes. Overall antibody specification was successful in 429 of 694 sera
      (61.8%) and in 175 of 240 patients (72.9%), respectively. The rate of antibodies
      against public epitopes shared by more than one HLA class I gene product was
      203/694 (29.3%) with respect to tested sera and 83/240 (34.5%) with respect to
      patients. The rate of public epitope antibodies was highest in sera with PRA
      values from 30 to 90% showing public epitope specificity in 159 of 353 sera
      (45.0%). CONCLUSIONS: We conclude that antibodies toward public HLA class I
      determinants are detectable not only in highly sensitized patients. The described
      program may increase the rate of antibody specification and facilitate the
      platelet supply in platelet refractory patients.

PMID- 7803997
TI  - [Autologous blood transfusion in tumor operations].
AB  - OBJECTIVE: The potential and limits of autologous transfusion in tumor patients
      are discussed according to the literature. New aspects are derived from own
      recent studies. DATA SOURCES AND SELECTION CRITERIA: The critical review of the
      German and English literature is based on a Medline and DIMDI backsearch covering
      the last 20 years. Own data not yet published are presented. RESULTS: Predeposit
      autologous blood represents an important and practical alternative to homologous
      transfusion also for tumor patients. Predeposit programs are limited by tumor
      anemia, the urgent time schedule for surgery, and the variable need for
      transfusions. Intraoperative autotransfusion is contraindicated in these
      patients. Our own studies on the presence of tumor cells in the blood shed from
      the surgical field during oncologic surgery confirm the concerns about a systemic
      spread of tumor cells after retransfusion. Further efforts aim to an elimination
      of contaminating tumor cells. In contrast to the literature filters for white
      blood cell depletion were found to fail to completely remove tumor cells. A 3
      log10 retention was measured. Proliferative activity of tumor cells was
      completely abolished by irradiation of the blood. CONCLUSIONS: Irradiation with
      50 Gy allows safe retransfusion of blood salvaged during tumor surgery. This
      promising possibility is now to be tested in clinical studies.

PMID- 7803996
TI  - Detection of primary HIV infection by a second-generation HIV(p24) antigen test.
AB  - We studied the course of a primary HIV infection in a 54-year-old woman. Probably
      the source of infection was sexual intercourse, since other risks, such as i.v.
      drug use, acupuncture and transfusion were excluded. On admission she presented
      with fever, a maculopapular rash, and moderate enlargement of nuchal lymph nodes.
      At that time the anti-HIV 1,2 enzyme immunoassay was negative. However, the HIV
      p24 Ag test, which was performed in every HIV screening in our laboratory, was
      positive. The suspicion of an acute HIV infection was supported by a positive HIV
      cDNA-PCR and confirmed by Western blot after seroconversion. As additional
      finding, the blood smear showed abnormal white cell differential count,
      indicating viral infection. Aminotransferases were slightly increased, and
      antibodies to hepatitis B surface and core antigens demonstrated former hepatitis
      B infection. It is concluded that in this case the HIV-p24 Ag test proved its
      suitability for early diagnosis of an acute HIV infection. In case of testing
      blood donors, none of the compulsory serological screening methods would have
      detected the HIV infection.

PMID- 7803998
TI  - 9th annual symposium on biotechnology: the new biology of carbohydrates.
      University College London Medical School, 16-17 December 1993.

PMID- 7803999
TI  - Glycobiology Group Colloquium on Advances in Structural Glycobiology, in honour
      of Professor Akira Kobata, held during the 649th meeting of the British
      Biochemical Society, Imperial College, London, December 20 1993.

PMID- 7804000
TI  - Enzymic synthesis of the trisaccharide core region of the carbohydrate chain of N
      glycoprotein.
AB  - Transmannosylation from mannotriose (Man beta 1-4Man beta 1-4Man) to the 4
      position at the nonreducing end N-acetylglucosaminyl residue of N,N'
      diacetylchitobiose was regioselectively induced through the use of beta-D
      mannanase from Aspergillus niger. The enzyme formed the trisaccharide Man beta 1
      4GlcNAc beta 1-4GlcNAc (3.7% of the enzyme-catalysed net decrease of N,N'
      diacetylchitobiose) from mannotriose as a donor and N,N'-diacetylchitobiose as an
      acceptor. Mannobiose (Man beta 1-4Man) was also shown to be useful as a donor
      substrate for the desired trisaccharide synthesis.

PMID- 7804001
TI  - Molecular species analysis of glycosphingolipids from small intestine of Japanese
      quail, Coturnix coturnix Japonica by HPLC/FAB/MS.
AB  - Neutral glycosphingolipids were isolated from quail small intestine and their
      structures were analysed. They contained: Gal beta 1-4GlcCer(LacCer), Gal alpha 1
      4GalCer(Ga2Cer), Gal alpha 1-4Gal beta 1-4GlcCer(Gb3Cer), GlcNAc beta 1-3Gal beta
      1-4GlcCer(Lc3Cer), GalNAc beta 1-4Gal beta 1-4GlcCer(Gg3Cer), GalNAc beta 1
      4[GalNAc beta 1-3] Gal beta 1-4GlcCer(LcGg4Cer), and GalNAc alpha 1-3GalNAc beta
      1-3Gal alpha 1-4Gal beta 1-4GlcCer (Forssman glycolipid) as well as
      glucosylceramide, galactosylceramide (Nishimura K et al. 1984) Biochim Biophys
      Acta 796:269-76) and the LeX glycolipid, III3 Fuc alpha-nLc4Cer (Nishimura K et
      al. (1989) J. Biochem (Tokyo) 101:1315-18). The molecular species compositions of
      these glycosphingolipids were examined using fast atom bombardment-mass
      spectrometry linked with reversed-phase high-performance liquid chromatography.
      By such analysis, we could classify the quail glycosphingolipids into at least
      three classes: glycolipids rich in species having four hydroxyl groups in the
      ceramides (GalCer, Gg3Cer, LcGg4Cer and LeX), those rich in the ceramides of N
      acyl trihydroxysphinganine with normal fatty acids (Lc3Cer), and glycolipids rich
      in the ceramides of N-acyl sphingenine with normal fatty acids (LacCer, Gb3Cer
      and Forssman glycolipid). Immunohistochemical observation implies that the
      differences in the hydrophobic moieties specified the localization of
      glycosphingolipids in the tissue.

PMID- 7804002
TI  - Tandem mass spectrometry for characterization of unsaturated disaccharides from
      chondroitin sulfate, dermatan sulfate and hyaluronan.
AB  - Fast atom bombardment tandem mass spectrometry has been used in the
      characterization of non-, mono-, di- and trisulfated disaccharides from
      chondroitin sulfate, dermatan sulfate and hyaluronan. The positional isomers of
      the sulfate group of mono- and disulfated disaccharides were distinguished from
      each other by both positive- and negative-ion fast atom bombardment tandem mass
      spectra, which gave sufficient information characteristic of the isomers. The
      anomeric isomers of nonsulfated disaccharides were characterized by the technique
      in the positive-ion mode. This fast atom bombardment collision induced
      dissociation mass spectrometry/mass spectrometry technique was also applied
      successfully to the characterization of trisulfated disaccharide.

PMID- 7804003
TI  - Glycosylation of glycoprotein 55 encoded by the anaemia-inducing strain of Friend
      spleen focus-forming virus.
AB  - Normal rat kidney cells, non-productively infected with the anaemia-inducing
      variant of Friend spleen focus-forming virus (F-SFFVA), were metabolically
      labelled with [2-3H]mannose. The primary translation product of the viral
      envelope gene (env), representing a glycoprotein with an apparent molecular M(r)
      of 55,000 (gp55), was isolated from cell lysates by immunoaffinity chromatography
      and purified by preparative SDS/PAGE. Radiolabelled oligosaccharides, released
      from tryptic glycopeptides by treatment with endo-beta-N-acetylglucosaminidase H,
      were characterized chromatographically, by enzymic digestion and by acetolysis.
      The results revealed that F-SFFVA gp55 obtained from this source carried
      predominantly oligomannose type sugar chains with five to nine mannoses. As a
      characteristic feature, glycans with seven to nine mannoses contained, in part,
      an additional glucose residue. Although the amount of glucosylated species found
      was higher in F-SFFVA gp55 (about 25% of total endo-H-sensitive oligosaccharides)
      than in gp55 of the corresponding polycythaemia-inducing variant (F-SFFVP,
      16.3%), the overall glycosylation pattern of the F-SFFVA env product closely
      resembled that of F-SFFVP gp55 [Strube et al. (1988) J Biol Chem 263:3762-71].
      Hence, our results demonstrate that the different intracellular processing and
      transport of the primary F-SFFVA env product cannot be attributed to aberrant
      trimming of its oligomannose type glycans.

PMID- 7804004
TI  - Gene structure of the 'large' sialidase isoenzyme from Clostridium perfringens
      A99 and its relationship with other clostridial nanH proteins.
AB  - Clostridium perfringens possesses two sialidase isoenzymes of different molecular
      weight. Almost 90% of the gene encoding the 'large' form was found on a 3.1 kb
      chromosomal fragment (Sau3AI) of strain A99 by hybridization with probes
      developed from the N-terminal protein sequence and from commonly conserved
      sialidase motifs ('Asp-boxes'), whereas the remaining 3'-terminal part was
      detected on a 2.1 kb fragment (Hind III) of chromosomal DNA. After combination of
      both fragments, the resulting E. coli clones expressed sialidase activity, the
      properties of the recombinant sialidase corresponding with those of the wild type
      enzyme. The entire chromosomal fragment of 3665 bp encompasses the complete
      sialidase gene of 2082 bp corresponding to 694 amino acids, from which a
      molecular weight of 72,956 for the mature protein can be deduced. The first 41
      amino acids are mostly hydrophobic and probably represent a signal peptide. The
      sialidase structural gene follows a non-coding region with an inverted repeat and
      a ribosome-binding site. Upstream from the regulatory region, another open
      reading frame (ORF) was detected. The 3'-terminus of the sialidase structural
      gene is directly followed by a further ORF of unknown function, which possibly
      encodes a putative permease or the acylneuraminate pyruvate-lyase involved in
      sialic acid catabolism. The primary structure of the 'large' isoenzyme is very
      similar to the sialidase of Clostridium septicum (55% identical amino acids),
      whereas the homology with the 'small' form of the same species is comparatively
      low (26%).

PMID- 7804006
TI  - The elimination of O-linked glycans from glycoproteins under non-reducing
      conditions.
AB  - A simple procedure is described for the elimination of O-linked glycans from
      bovine submaxillary mucin under non-reducing conditions, using triethylamine in
      aqueous hydrazine. The glycans were isolated as the hydrazones, which were
      converted to the reducing glycans by exchange with acetone in neutral aqueous
      solution. The glycan alditols obtained after reduction corresponded to those
      obtained by the reductive beta-elimination of O-glycans.

PMID- 7804005
TI  - The ganglioside GD1 alpha' IV3Neu5Ac, III6Neu5Ac-GgOse4Cer, is a major
      disialoganglioside in the highly metastatic murine lymphoreticular tumour cell
      line MDAY-D2.
AB  - The aim of the present study was to investigate the ganglioside expression of the
      highly metastatic murine lymphoreticular tumour cell line MDAY-D2. Cells were
      propagated under controlled pH conditions and oxygen supply in bioreactors of 1
      and 7.5 l volumes by repeated batch fermentation. Gangliosides were isolated from
      2.7 x 10(11) cells, purified by silica gel chromatography and separated into mono
      and disialoganglioside fractions by preparative DEAE anion exchange high
      performance liquid chromatography. Individual gangliosides were obtained by
      preparative thin layer chromatography. Their structural features were established
      by immunostaining, fast atom bombardment and gas chromatography mass
      spectrometry. In addition to gangliosides of the GM1a-pathway (GM2, GM1a and
      GD1a) and GM1b (IV3Neu5Ac-GgOse4Cer) and GalNAc-GM1b of the Gm1b-pathway, the
      disialoganglioside GD1 alpha (IV3Neu5Ac, III6Neu5Ac-GgOse4Cer) was found in equal
      amounts compared to GD1a (IV3Neu5Ac, II3Neu5Ac-GgOse4Cer). All gangliosides were
      substituted with C24:0, 24:1 and C16:0 fatty acids, sphingosine and N
      acetylneuraminic acid as the sole sialic acid.

PMID- 7804007
TI  - A general approach to the synthesis of O- and N-linked glycopeptides.

PMID- 7804008
TI  - Molecular modelling of secondary and tertiary structures of hyaluronan, compared
      with electron microscopy and NMR data. Possible sheets and tubular structures in
      aqueous solution.
AB  - Electron microscopy shows that hyaluronan (HA) forms sheets and tube-like
      structures in solution. Molecular modelling by Tartu plastic space-filling atomic
      models revealed that hydroxymethyl and carboxylate groups of HA anti-parallel
      chains can be joined by H-bonds. Using these bonds, HA molecules can be modelled
      as sheets and tubules. These tertiary structures have three kinds of lateral
      contact: (1) antiparallel chains stacked by hydrophobic patches; (2) parallel
      chains joined by both stacking interactions and H-bonds; and (3) crossing chains
      joined by H-bonds and stacking interactions. Sheet and tubular structures may
      explain some viscoelastic and biological properties of HA.

PMID- 7804009
TI  - The role of calcium and N-linked glycans in the oligomerization and carbohydrate
      binding properties of human immunodeficiency virus external envelope
      glycoprotein.
AB  - Envelope glycoproteins of human immunodeficiency virus (gp120 and gp41) occur as
      oligomers. Here, we show by gel filtration analysis that gp120 oligomerization in
      vitro is calcium- and temperature-dependent. Recombinant gp120 (rgp120) species
      were recovered as monomers at 20 degrees C in the absence of calcium, but as
      tetramers at 37 degrees C in 10 mM CaCl2. Under the latter condition, N-glycanase
      deglycosylated rgp120 formed hexamers. Relative to intact rgp120, which has been
      reported to display carbohydrate-binding properties for N-acetyl-beta-D
      glucosaminyl and mannosyl residues, deglycosylation enhanced rgp120 specific
      binding to mannose-divinylsulfone-agarose, para-aminophenyl-beta-D-GlcNAc-agarose
      and fetuin-agarose matrices. Taken together, these results rule out the role of
      homologous lectin-carbohydrate interactions via N-linked glycans in the rgp120
      oligomerization, even though its lectin properties may also be calcium-dependent.
      Deglycosylation may unmask domains of rgp120 polypeptide backbone that
      independently play a role either in rgp120 lectin activity or in calcium
      dependent oligomerization.

PMID- 7804010
TI  - In vitro production of proteoglycans in the articular-epiphyseal cartilage of
      growing pigs.
AB  - The failure of cartilage mineralization in osteochondrotic cartilage may be due
      to an impaired proteoglycan production. The in vitro production of proteoglycans
      was therefore studied in the joint cartilage of growing pigs, aged 9-18 weeks,
      after incubation of cartilage samples with 35S-sulfate. Cartilage was obtained
      from different areas of the femoral condyles and samples from these areas were
      further divided into three layers, where the superficial layer contains articular
      cartilage and the basal layers consist of growth cartilage. There was no
      significant difference in the overall amount of 35S-proteoglycans synthesized in
      different areas of the condyles. However, the total production of 35S
      proteoglycans per mg tissue was highest in the basal layer in all areas. This was
      not due to a larger number of cells; the superficial layer contained more DNA per
      mg tissue than the basal layer. Gel chromatography on Sepharose CL-2B of the
      cartilage extracts, which resulted in the separation of large proteoglycans (Kav
      approximately 0.4) from proteoglycans of small hydrodynamic size (Kav
      approximately 0.8), showed that the relative amount of large proteoglycans
      increased with the distance from the articular surface. Again, no difference in
      the relative amounts of large and small proteoglycans were found when cartilage
      from different areas were compared. Osteochondrotic cartilage was detected in the
      pigs aged 12-18 weeks. In areas where osteochondrotic cartilage were present, the
      total production of 35S-proteoglycans was lowered and the relative amount of
      large proteoglycans was less than that found in the adjoining areas devoid of
      osteochondrotic lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7804011
TI  - Identification and characterization of the Sda beta 1,4,N
      acetylgalactosaminyltransferase from pig large intestine.
AB  - The high occurrence in large intestine epithelial cells from pig of a beta-N
      acetylgalactosaminyltransferase with a substrate specificity very similar to that
      of the Sda beta 1,4-N-acetylgalactosaminyltransferase from other tissues is
      reported. The enzyme strictly recognized the NeuAc alpha 2,3Gal beta terminal
      sequence of N- and O-linked oligosaccharides bound to glycoproteins. The
      transferase activity required Mn2+ and an optimum pH of 7.4. In contrast to the
      kidney Sda-enzyme from humans and other mammals, the microsomal fraction of pig
      colonic cells expressed a very high activity even in the absence of Triton X-100.
      A rapid procedure is presented for the large scale preparation of GalNAc beta
      1,4(NeuAc alpha 2,3)Gal beta 1,4Glc from NeuAc alpha 2,3Gal beta 1,4Glc. The
      biosynthesized tetrasaccharide was completely resistant to the action of
      neuraminidase from Vibrio cholerae, whereas about 60% of N-acetylneuramic acid
      was cleaved by neuraminidase from Newcastle disease virus. HPLC separation of
      different compounds is reported.

PMID- 7804013
TI  - Detection by the CAGE of alcoholism or heavy drinking in primary care outpatients
      and the general population.
AB  - There is a need to improve the diagnosis of alcoholism in clinical settings
      because alcoholism, particularly in its early stages, is often unrecognized in
      general medical practice and in hospitals. In this study the CAGE questionnaire
      was used to detect alcoholism or heavy drinking in three populations, namely,
      alcoholics in treatment (ALC), primary-care outpatients (PC), and the general
      population (GP). Nearly all the ALC tested positive on the CAGE (97.8%), both for
      current (past year) and for lifetime alcohol-related problems. Among the PC
      subjects, 44.8% tested positive for lifetime alcohol problems, but the prevalence
      decreased to 17.2% when only past-year problems were considered. Likewise, 38.3%
      of the GP sample tested positive for lifetime, but half of these did not meet the
      1-year recency criterion. Compared to DSM-III-R criteria during the same time
      intervals, the sensitivity/specificity of the lifetime CAGE was 91.2%/84.0% and
      76.9%/85.1% in the PC and GP, respectively. The corresponding
      sensitivity/specificity of the past-year CAGE was 94.4%/97.0% and 74.6%/91.6%,
      respectively. Thus, the CAGE is an appropriate screening test for alcohol
      problems in these two populations, but other confirmatory tests or interviews are
      necessary to eliminate false positives. There were neither gender nor racial
      differences in the ALC sample responses to individual CAGE questions. However,
      there were gender differences in the PC and GP samples, with more males
      responding yes to each of the questions. The gender differences probably
      reflected the higher prevalence of heavy drinking and alcoholism among males.

PMID- 7804012
TI  - An improved method for the measurement of total lipid-bound sialic acids after
      cleavage of alpha 2,8 sialic acid linkage with Vibrio cholerae sialidase in the
      presence of cholic acid, SDS and Ca2+.
AB  - In the measurement of total lipid-bound sialic acids involving periodic acid
      oxidation, as in the periodate-resorcinol assay, the inner sialic acids of
      disialoglycolipids (such as GD3 and GD2) are not involved because their alpha 2,8
      ketosidic linkages are resistant to periodic acid oxidation, even after
      acid/enzyme hydrolysis or alkali pretreatment. However, the sialic acids from
      these glycolipids can be recovered completely after cleavage of alpha 2,8
      linkages by V. cholerae sialidase in the presence of cholic acid, sodium dodecyl
      sulphate and calcium. Interestingly, removal of calcium or detergent(s) or both
      significantly minimizes the sialidase action on the disialyl residues of these
      gangliosides. Therefore, we recommend sialidase (Vibrio cholerae) pretreatment of
      the glycolipids in the presence of cholic acid, SDS and Ca2+ for complete
      recovery of sialic acids from di- and polysialogangliosides and for accurate
      measurement of total lipid-bound sialic acids by periodate-resorcinol assay.

PMID- 7804014
TI  - The effects of parental influences and respondents' norms and attitudes on black
      and white adult drinking patterns.
AB  - A model predicting drinking patterns among adult respondents from parental
      influences and respondents' norms and attitudes was tested with data from a
      nationwide survey of 1,947 black and 1,777 white Americans. The results showed
      that relationships between parental drinking background, respondents' norms and
      attitudes, and respondents' drinking behavior are identical for blacks and
      whites. Among both groups, parental influences are indirect and have a moderate
      influence on the respondents' norms and attitudes, which in turn are the most
      powerful predictors of drinking behavior. However, racial differences did emerge
      in the model, and they illustrate that race moderates relationships between
      social characteristics and norms, parental demographics and parent drinking
      attitudes and behavior, and respondents' social characteristics and drinking
      patterns. These differences were traced to religion, social status, and cultural
      variation between the two groups.

PMID- 7804015
TI  - The motivational correlates of drinking, smoking, and illicit drug use during
      pregnancy.
AB  - Despite attempts to eliminate the consumption of alcohol, tobacco, and other
      substances of abuse by women of childbearing age, especially during gestation,
      apparently many do not curtail these negative lifestyle behaviors, as evidenced
      by the number of poor birth outcomes and developmentally disabled children born
      each year. This study examined the relationship of depression, attitude toward
      pregnancy, a number of sociodemographic variables, and substance use by women of
      child-bearing age prior to and after learning of their pregnancies. Results
      indicated that attitude independently, and depression independently and in
      interaction with socio-demographic factors are associated with substance use at
      both time points. From this we conclude that preventive efforts should be
      designed and targeted at those women who are depressed, especially those who have
      the sociodemographic characteristics associated with heavier substance use.

PMID- 7804016
TI  - Patterns of cocaine use and HIV infection among injection drug users in a
      methadone clinic.
AB  - To investigate patterns of cocaine use, a total of 440 injection drug users
      (IDUs) in two consecutive cohorts were recruited from a methadone maintenance
      program in New York City. IDUs who had injected cocaine more frequently during
      the prior year were more likely to be found HIV positive than IDUs who had
      injected cocaine less frequently, even after controlling for age, gender, and
      ethnicity. The study investigated noninjecting cocaine use among IDUs, such as
      snorting and smoking cocaine, which is often overlooked in epidemiological
      research investigating the relationship between HIV infection rate and drug use
      behaviours among IDUs. This study revealed that older IDUs were more likely to
      use IV cocaine and speedball, whereas younger IDUs were more likely to use crack
      or snort cocaine. In the 1987 cohort, after statistically controlling for age,
      analyses revealed that Hispanic IDUs snorted cocaine more frequently than other
      groups, and that black female IDUs used crack more frequently than other groups.
      Future research should investigate whether these crack and cocaine users,
      particularly black and Hispanic female IDUs, have changed their drug behaviors
      because of an awareness of the high risk of IV drug use for HIV infection, or
      whether they have started using these drugs as stepping stones for future IV
      cocaine and speedball use.

PMID- 7804017
TI  - General and specific locus of control in cocaine abusers.
AB  - Although the struggle for control has been widely recognized as a central feature
      of addiction, information about its role in the development and maintenance of
      addictive behavior is limited. This study compared general and specific locus of
      control in three groups of cocaine abusers: (a) hospitalized subjects with no
      prior treatment experience, (b) hospitalized subjects with prior treatment
      experience, and (c) recovering cocaine abusers. Results of initial analyses of
      variance revealed significant group differences on both general and specific
      scales. Scores of recovering cocaine abusers were more internal than those of
      hospitalized subjects. Differences on the general scale were not significant when
      age was controlled. No significant differences were noted between the two groups
      of hospitalized subjects, but scores of hospitalized cocaine abusers made an
      internal shift over the course of treatment. These findings support
      generalizability of models previously applied to alcoholics and suggest that
      internality is positively correlated with recovery.

PMID- 7804018
TI  - Personal and environmental risk factors as predictors of alcohol use, depression,
      and treatment-seeking: a longitudinal analysis of late-life problem drinkers.
AB  - We examined how personal risk factors (prior functioning, male, unmarried, early
      onset of drinking problems, and avoidance coping) and environmental risk factors
      (negative life events, chronic stressors, and friends' approval of drinking)
      predicted changes in older problem drinkers' (N = 659) adaptation over a 1-year
      interval. Personal risk factors independently predictive of poorer outcomes
      included poorer prior functioning, being male, and more use of avoidance coping
      strategies. Of environmental risk factors, negative life events, chronic health
      and spouse stressors, and having more friends who approved of drinking were
      independent predictors of poorer follow-up functioning and treatment seeking.
      Interactions between personal and environmental risk factors helped predict
      subsequent alcohol consumption and treatment seeking. For example, lighter
      drinkers were more likely than heavier drinkers to curtail alcohol use in
      response to new health events; friends more strongly influenced the treatment
      seeking of unmarried problem drinkers and individuals who used more avoidance
      coping strategies.

PMID- 7804019
TI  - The long- and short-term effects of marriage on drinking.
AB  - Descriptive and multiple regression analyses of data from the National
      Longitudinal Survey of Youth (NLSY), a longitudinal survey conducted annually
      since 1979, offer support for the many studies that demonstrate a relationship
      between marital status and alcohol consumption. Race, gender, history of heavy
      drinking, and alcoholic relatives were additional key variables utilized in the
      analysis. Data from this ongoing survey indicate that long-term marriage is
      associated with decreased drinking, except among women with a history of heavy
      drinking. Separation and divorce are not associated with long-term effects on
      current drinking. Divorce is associated with decreased drinking, at least in the
      short term, for men and women with a family history of alcoholism.

PMID- 7804020
TI  - Beliefs about the causes of substance abuse: a comparison of three drugs.
AB  - Respondents were randomly assigned to one of three conditions and completed a
      questionnaire asking about their beliefs regarding the causes of alcohol abuse,
      cocaine abuse, or cigarette smoking, and about their humanitarian attitudes
      toward substance abusers. Three major findings emerged: (a) compared to the other
      substances of abuse, the disease concept was most strongly endorsed for alcohol
      abuse, the sin conception for cocaine abuse, and the habit conception for
      smoking; (b) for alcohol abuse only, endorsement of the disease concept was
      positively related to humanitarian attitudes; and (c) for all three substance
      types, the sin conception was negatively related to the expression of
      humanitarian attitudes. Implications of these findings are discussed.

PMID- 7804021
TI  - Effects of menstrual phase on nicotine, alcohol, and caffeine intake in smokers.
AB  - To determine whether cigarette smoking and other drug use are affected by
      menstrual phase, daily diaries rating menstrual symptomatology, smoking, and
      alcohol and caffeine intake in female smokers were examined. Women with
      premenstrual symptomatology were excluded. Menstrual symptomatology peaked during
      menses and was accounted for primarily by symptoms indicative of physical
      discomfort. Smoking did not differ as a function of menstrual phase, nor did
      there emerge any systematic intrasubject correlation between symptomatology and
      smoking. Alcohol and caffeine intake also failed to show phase-related
      differences. It was concluded that substance intake is highly stable across the
      menstrual cycle in female smokers.

PMID- 7804022
TI  - Effects of menstrual phase on intake of nicotine, caffeine, and alcohol and
      nonprescribed drugs in women with late luteal phase dysphoric disorder.
AB  - To investigate the possibility that cigarette smoking and other drug use are
      affected by menstrual phase in smokers with Late Luteal Phase Dysphoric Disorder
      (LLPDD), we examined daily diaries rating menstrual symptomatology, smoking,
      alcohol and nonprescription drug use, and caffeine intake in nine female smokers
      meeting criteria for LLPDD. Menstrual symptomatology peaked during the
      premenstrual phase. Smoking, alcohol, and nonprescription drug intake were
      increased during menses; caffeine intake was unaffected by phase. No systematic
      intrasubject correlation between symptomatology and smoking was detected. It was
      concluded that in women with LLPDD, smoking and alcohol and nonprescription drug
      intake appear to vary as a function of menstrual phase. The lack of intrasubject
      correlations between symptomatology and intake, and the failure of peak intake to
      coincide with peak symptomatology, however, indicate that these effects cannot be
      explained simply as "self-medication" of acute episodes of dysphoric mood.

PMID- 7804024
TI  - Experimental model of lead nephropathy. IV. Correlation between renal functional
      changes and hematological indices of lead toxicity.
AB  - Adverse effects on hematopoiesis and renal function have been reported in both
      animals and humans exposed to high doses of lead for a protracted period of time,
      but little is known about the interrelationship between these two target organ
      systems. The present study examines rats exposed via drinking water to high dose
      (5000 mg/L) or low dose (100 mg/L) lead, either continuously or discontinuously,
      for periods ranging from 1 to 12 months. In addition to blood lead, indices of
      hematological abnormalities included hematocrit, zinc protoporphyrin (ZPP) and
      red blood cell (RBC) membrane sodium-potassium-activated adenosine triphosphatase
      (Na-K-ATPase). Renal function abnormalities were assessed by measurements of
      glomerular filtration rate (GFR) by the single injection 125-I-iothalamate
      technique and urinary excretion of the proximal renal tubular enzyme, ligandin.
      Blood lead and GFR correlated positively during the first 6 months of lead
      administration, reflecting a stimulatory effect of lead on renal hypertrophy and
      GFR during this time period. When this distorting effect was factored out, there
      were few residual correlations between renal and hematological abnormalities. The
      only significant relationship between GFR and hematological parameters of lead
      toxicity was a negative correlation between GFR and RBC membrane Na-K-ATPase in
      animals treated with high dose lead for 6 months and observed at the end of 12
      months (discontinuous group).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7804023
TI  - Protein technics for selenium speciation in human body fluids.

PMID- 7804025
TI  - Trace element concentrations in hair of subjects from two South Pacific Islands,
      Atafu (Tokelau) and Kitava (Papua New Guinea).
AB  - The concentrations of trace elements in hair were measured in 108 healthy
      subjects (60 males and 48 females, mean age 46-years) resident on Atafu (Tokelau)
      and in 83 subjects (63 males and 20 females, mean age 26-years) living on Kitava
      island (Papua New Guinea). On Kitava, a traditional subsistence lifestyle
      uninfluenced by Western dietary habits is still maintained, but on Atafu the
      dietary habits have been modified by the inclusion of such imported foods as
      rice, flour, sugar and canned meat and fish. The concentrations of zinc and
      magnesium in hair were significantly higher in the Kitava than in the Atafu
      subjects, whereas those of copper were similar in both groups, and those of
      selenium, mercury, lead and cadmium were higher in Atafu subjects. The levels of
      serum copper, magnesium and selenium concentrations in Kitava subjects were not
      so low as to indicate any trace element deficiency. The higher hair content of
      mercury, lead and cadmium found among Atafu subjects might be due to consumption
      of marine foods contaminated with metals, consumption of canned foods, or
      frequent cigarette smoking, though it is difficult to single out any specific
      factor.

PMID- 7804027
TI  - Ontogenic changes in the nephrotoxicity of chromate correlate with the
      glutathione oxidoreduction system.
AB  - The role of GSH concentration and GSSG reductase activity in age differences in
      chromate nephrotoxicity was investigated. Young and adult rats were injected with
      2 and 1 mg sodium chromate/100 g body weight (BW), respectively, which led to
      equal Cr concentrations in renal tissue. Cr nephrotoxicity was lower in young
      than in adult rats. It was shown that from 30 minutes after the chromate
      injection GSSG reductase activity in renal tissue was increased in adult but
      decreased in young rats by the chromate. GSSG reductase activity was increased in
      young rats by pretreatment with phenobarbital. The consequence was an enhancement
      of chromate nephrotoxicity as shown by proteinuria. Renal GSH concentration is
      lower in young rats and limiting for chromate reduction in vitro in these
      animals. Therefore, GSH concentration was increased by pretreatment with N
      acetylcysteine, which enhanced chromate nephrotoxicity significantly. These
      results reflect the important role of the GSH oxidoreduction system in chromate
      nephrotoxicity and its relationship to age differences.

PMID- 7804026
TI  - Accumulation of aluminum in cancers of the liver, stomach, duodenum and mammary
      glands of rats.
AB  - The aim of the present investigation was to evaluate abnormal changes in trace
      element concentrations during carcinogenesis. First, Al, Zn and Cu in the liver
      tissues of rats were measured by atomic absorption analysis over a half year of
      hepatocarcinogenesis. Male Wistar rats were given carcinogenic food containing
      600 mg/kg of 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB) in a basal diet for
      several months. After 4 to 6 months of feeding, hepatocarcinomas developed in the
      rats. Zn and Cu concentrations in the hepatocarcinomas of the 3'-MeDAB group
      significantly decreased as compared with normal liver tissues of the control
      groups. On the other hand, the aluminum concentration in the hepatocarcinomas was
      more than three times that in the normal liver tissues. The Al and Se contents of
      developed gastric and mammary cancers were measured in Experiment II. Male and
      female rats were given 1-methyl-3-nitrothoguanidine(MNNG) and 2,7
      dimehtylbenz(a)anthracene(DMBA), respectively. After several months, carcinomas
      developed in over half of the rats. The Al and Se concentrations in cancers,
      livers and the blood were determined by atomic absorption analysis. It was shown
      that both gastric and mammary carcinomas contained a high level of aluminum and
      very little selenium in comparison with normal liver tissues. The present study
      demonstrated that aluminum accumulated in experimentally induced carcinomas in
      rats, i.e., cancers of the liver, stomach, duodenum and mammary glands.

PMID- 7804028
TI  - Ultramicroanalysis of dental plaque films by total reflection X-ray fluorescence.
AB  - Microgram quantities of dental plaque were taken near amalgam fillings, gold
      crowns and intact teeth. Such extremely small samples can be analysed by total
      reflection X-ray fluorescence (TXRF), a fairly new variant of energy dispersive X
      ray fluorescence (EDXRF). More than sixty samples were examined directly without
      chemical pretreatment. Fifteen elements of interest were detected simultaneously
      within a wide range of mass fraction and with detection limits of several mg/kg.
      A significant correlation of the Hg-accumulation in plaque and the amalgam
      fillings was established. Near these fillings Hg mass fractions can reach a level
      of 300 mg/kg. The results for other elements, e.g. Au, are less significant.

PMID- 7804029
TI  - Selenium concentration in plasma and erythrocytes in a healthy Slovak population.
AB  - To obtain reference values for plasma and erythrocyte selenium concentrations
      blood specimens were collected from healthy adults from the Bratislava region. In
      174 people, 20 to 60 years old, a plasma Se concentration of 56.2 +/- 8.5
      micrograms/L and in 133 persons an erythrocyte Se level of 95.3 +/- 16.3
      micrograms/kg were found (mean +/- SD). Selenium levels showed a normal
      distribution in plasma and erythrocytes. No differences were found according to
      sex or age. These results indicate that the Slovak population has a low Se
      status, with values for plasma Se being among the lowest in Europe.

PMID- 7804030
TI  - Incidence of subclinical lead (Pb) exposure in cattle of an industrial area in
      Greece.
AB  - The incidence of subclinical lead (Pb) poisoning was investigated in the cattle
      population of an industrial area in northern Greece. The cattle were divided into
      two groups with respect to their alleged exposure to Pb, which was assayed by
      determining whole blood and hair Pb concentration and erythrocyte delta
      aminolevulinic acid dehydratase (ALA-D) activity. The cows which were located
      closer to potential contamination sources were found to have higher (P < 0.05)
      blood and hair Pb content, whereas no significant differences were noted in ALA-D
      activity. Hair Pb increased significantly (P < 0.05) with age, an observation
      which should lead to further, more extensive research, in order to evaluate the
      possibility of using hair as indicator of chronic Pb intake.

PMID- 7804032
TI  - Selenium status in Turkey. II. Serum selenium concentration in healthy residents
      of different ages in Ankara.
AB  - In this study we determined the serum selenium concentraction of 218 healthy
      individuals at different ages, in Ankara, using a spectrofluorimetric method. The
      mean selenium levels were found to be 45 +/- 10 micrograms/L in cord blood at
      birth; 69 +/- 13 micrograms/L in 2 month-12 month-old infants; 77 +/- 12
      micrograms/L in children aged > 12 months-16 years; and 74 +/- 16 micrograms/L in
      adults aged 18-48 years. Selenium concentrations showed age dependency,
      increasing significantly in childhood but decreasing after 40 years of age. No
      relation to the sex, dietary habits, socioeconomical status or hematological
      parameters such as hemoglobin concentration and white blood cell count, was
      observed. The results obtained thus suggest that the status of selenium in Ankara
      residents is in a range that could be considered as safe and adequate.

PMID- 7804031
TI  - Selenium concentration and glutathione peroxidase activity in blood of children
      with cancer.
AB  - In this work we studied 205 children with cancer, aged 6 months to 7 years, who
      had been diagnosed as suffering from various types of neoplasm. In blood of these
      children we determined the selenium concentration and glutathione peroxidase
      activity by fluorometric and spectrophometric methods, respectively. The control
      group consisted of 128 healthy children. In all groups of children with cancer we
      observed a significantly lower selenium concentration and lowered glutathione
      peroxidase activity. We found statistical differences in selenium concentration
      between first or second and third, and between first and fourth or fifth stages
      of the disease, only in 3-7 year-old patients. Glutathione peroxidase activity
      was statistically depressed in the same age group between the first or second and
      third stages of the disease. Generally, there were no differences in the
      concentration of the microelement or in the glutathione peroxidase activity
      between children before and during treatment with cytostatics.

PMID- 7804033
TI  - Leadership: an opportunity. International Leadership Extern Program.

PMID- 7804034
TI  - Increasing inequalities in the health of the nation.

PMID- 7804035
TI  - Beyond health care.

PMID- 7804036
TI  - Liver biopsy: blind or guided?

PMID- 7804037
TI  - Gift authorship: a poisoned chalice?

PMID- 7804038
TI  - Clinical guidelines in 1994.

PMID- 7804040
TI  - Shanghai bans public smoking.

PMID- 7804039
TI  - Obstetrician suspended after research inquiry.

PMID- 7804041
TI  - Doctors sued for uninterest, say researchers in US.

PMID- 7804042
TI  - Gulf veteran gets pension for desert fever.

PMID- 7804043
TI  - Agencies unite to prevent child deaths.

PMID- 7804044
TI  - Israeli government puts squeeze on public hospitals.

PMID- 7804045
TI  - NHS at risk from fraud, warns Audit Commission.

PMID- 7804046
TI  - Deprivation and mortality in Scotland, 1981 and 1991.
AB  - OBJECTIVE: To compare the mortality experience of Scottish postcode sectors
      characterised by socioeconomic census variables (Carstairs scores) in 1980-2 and
      1990-2. METHODS: Variables derived from the 1981 and 1991 censuses were combined
      according to the method devised by Carstairs and Morris to obtain Carstairs
      scores for 1010 postcode sectors in Scotland in 1981 and 1001 sectors in 1991.
      For most analyses, these scores were grouped into seven deprivation categories
      ranging from affluent (category 1) to deprived (category 7) localities. MAIN
      OUTCOME MEASURES: Death rates and standardised mortality ratios for localities
      according to deprivation category. RESULTS: Postcode sectors in Scotland that
      were categorised as deprived in 1981 were relatively more deprived at the time of
      the 1991 census; the mortality experience of deprived localities relative to
      either Scotland or affluent neighbourhoods worsened over this period, with a 162%
      difference between the most affluent and most deprived categories in 1991-2.
      Although the age and sex standardised mortality for ages 0-64 in Scotland
      declined by 22% during the 1980s, the reduction in the deprived categories was
      only about half that of the affluent groups. Increases in the death rate for men
      (29%) and women (11%) aged 20-29 in the deprived groups were largely attributable
      to an increase in the rates of suicide. Death rates from ischaemic heart disease
      and carcinoma of the lung and bronchus at ages 40-69 were lower in all
      deprivation categories in 1990-2, but the reduction was greater in more affluent
      areas; the difference in rates for these conditions between affluent and deprived
      groups therefore increased over the decade. The observed worsening of the
      standardised mortality ratio for Glasgow relative to Scotland could be explained
      on the basis of these mortality differentials and the concentration of deprived
      postcode sectors in Glasgow. CONCLUSIONS: Differences in mortality experience
      linked to relative poverty increased in the 10 years between 1981 and 1991
      censuses. Although mortality for Scotland as a whole is improving, the picture is
      one of an increasing distinction between the experience of the majority and that
      of a substantial minority of the population.

PMID- 7804047
TI  - Higher mortality in deprived areas: community or personal disadvantage?
AB  - OBJECTIVE: To investigate the association between level of social deprivation in
      electoral wards and premature mortality among residents, before and after
      allowing for levels of personal deprivation. DESIGN: Longitudinal study of the
      Office of Population Censuses and Surveys. SETTING: England. SUBJECTS: Random
      sample of nearly 300,000 people aged between 16 and 65 at the 1981 census and
      followed up for nearly nine years. MAIN OUTCOME MEASURE: Death from all causes
      between ages of 16 and 70. RESULTS: Without allowance for personal disadvantage,
      both sexes showed a clear, significant, and roughly linear positive relation
      between degree of deprivation of the ward of residence in 1981 and premature
      death before 1990. For men, this association was effectively explained away once
      allowance was made for individual socioeconomic circumstances. For women living
      in wards of above average deprivation, the association was also effectively
      removed, but the situation for other women was less clear. CONCLUSION: The excess
      mortality associated with residence in areas designated as deprived by census
      based indicators is wholly explained by the concentration in those areas of
      people with adverse personal or household socioeconomic factors. Health policy
      needs to target people as well as places.

PMID- 7804048
TI  - Birth weight and later socioeconomic disadvantage: evidence from the 1958 British
      cohort study.
AB  - OBJECTIVE: To investigate the relation between birth weight and socioeconomic
      disadvantage during childhood and adolescence in a birth cohort study. DESIGN:
      Longitudinal analysis of birth weight in relation to social class, household
      amenities and overcrowding, and financial difficulties as reported by parents at
      interview when participants were aged 7, 11, and 16 years; and receipt of
      unemployment or supplementary benefits as reported by participants at age 23.
      SUBJECTS: Male participants in the 1958 birth cohort (national child development
      study) born to parents resident in Great Britain during the week of 3-9 March
      1958. Data on birth weight and financial difficulties between birth and 23 years
      were available for 4321; data on housing conditions and social class at ages 7,
      11, and 16 years were available for 3370. MAIN OUTCOME MEASURES: Socioeconomic
      disadvantage at later ages in men weighing 6 lb (2721g) or under at birth
      compared with those weighing over 6 lb and between fifths of the distribution of
      birth weight. RESULTS: Cohort members who weighed 6 lb or under at birth were
      more likely to experience socioeconomic disadvantage subsequently. Those in lower
      fifths of the distribution were more likely to experience socioeconomic
      disadvantage. CONCLUSION: Low birth weight is associated with socioeconomic
      disadvantage in childhood and adolescence. Studies of the association of
      indicators of early development and adult disease need to take into account
      experiences right through from birth to adulthood if they are to elucidate the
      combination of risks attributable to developmental problems and socioeconomic
      disadvantage.

PMID- 7804049
TI  - Socioeconomic deprivation and health and the ecological fallacy.

PMID- 7804050
TI  - Socioeconomic deprivation in Britain. Appropriateness of deprivation indices must
      be ensured.

PMID- 7804051
TI  - Relation between rates of leg amputation and distal arterial reconstructive
      surgery. Oxford Regional Vascular Audit Group.

PMID- 7804052
TI  - Confounding and Simpson's paradox.

PMID- 7804053
TI  - Deprivation and mortality in Glasgow: changes from 1980 to 1992.

PMID- 7804054
TI  - Survey of fulfillment of criteria for authorship in published medical research.

PMID- 7804055
TI  - Comparison of patient questionnaire, medical record, and audio tape in assessment
      of health promotion in general practice consultations.
AB  - OBJECTIVE: To determine what proportion of health promotion activities reported
      by the patient is recorded in the general practice notes and to compare these
      methods of assessing health promotion with audio tape analysis. DESIGN: Secondary
      analysis of data obtained in a controlled trial of differing appointment lengths.
      After each consultation the medical record was examined and the patient invited
      to completed a questionnaire. A subsample of consultations was audio taped.
      SETTING: Nottinghamshire. SUBJECTS: 16 general practitioners from 10 practices.
      This report includes 3324 consultations with patients aged > or = 17, with data
      on measurement of blood pressure and advice about smoking and alcohol. RESULTS:
      Data from questionnaire and medical notes were available for 2281 consultations.
      Advice on smoking was recorded in the notes in 30.9% of cases in which a patient
      reported it (for alcohol and measurement of blood pressure, 44.4% and 82.7% of
      cases respectively). In 516 cases analysis of audio tape and review of records
      was performed. Advice on smoking was recorded in the patient's notes in 28.6% of
      cases in which it was detected on audio tape (for alcohol, 31.1% of cases). In
      335 consultations data from audio tape and questionnaire were available. Advice
      on smoking was reported by patients in 73.9% of cases in which it was detected on
      audio tape (for alcohol, 75.0% of cases). CONCLUSIONS: Review of the medical
      record is a reasonably accurate method of assessing measurement of blood pressure
      in the consultation but would lead to significant underestimation of advice about
      smoking and alcohol.

PMID- 7804056
TI  - Are general practitioners equipped to manage acute severe asthma?

PMID- 7804057
TI  - Socioeconomic inequalities in health in The Netherlands: impact of a five year
      research programme.
AB  - The attention paid to the socioeconomic inequalities in health in the Netherlands
      has increased greatly in recent years. A national research programme was started
      in 1989, and among other things, this has increased the yearly number of
      publications on socioeconomic inequalities in health by about 25%. The programme
      has increased awareness of inequalities among researchers and policy makers as
      well as improved the information available on health inequalities and the reasons
      for them. Cross party agreement on the need to reduce these inequalities has led
      to a consensus based approach which contrasts with the heavily politicised debate
      in countries such as the United Kingdom.

PMID- 7804058
TI  - WHO in retreat: is it losing its influence?
AB  - WHO says it has three main functions: to set normative standards; to provide
      technical advice and assistance on medical matters; and to advocate changes in
      health policy. During its 46 year history the first two functions have been a
      constant and uncontroversial backbone through which WHO has earned its reputation
      for scientific excellence. The third function, advocacy, came to the fore with
      the launch of Health for All in 1977, after which WHO took a key role in
      influencing international health policy. WHO's friends and critics alike now say
      that the organisation is losing its influence and retreating into its technical
      and biomedical shell. This article maps the changes in WHO's approach over the
      past 46 years and considers whether fears about its loss of influence are
      justified.

PMID- 7804059
TI  - Nocardia pericarditis.

PMID- 7804060
TI  - Is routine computed tomography in strokes unnecessary?

PMID- 7804061
TI  - Is routine computed tomography in strokes unnecessary? Costs outweigh benefits.
AB  - Until the results of early intervention trials are known, computed tomography
      should be used selectively rather than routinely in all patients with stroke.
      Scanning may be advised in young patients (under 65 years) or in those with an
      atypical course where there is diagnostic doubt and computed tomography would
      influence management. The cost and medicolegal implications of routine scanning
      are enormous and should be considered carefully in relation to other and possibly
      more effective strategies.

PMID- 7804062
TI  - ABC of breast diseases. Metastatic breast cancer.

PMID- 7804063
TI  - Glycated haemoglobin values. Methodological discrepancies are not important.

PMID- 7804064
TI  - Glycated haemoglobin values. Derive reference range locally.

PMID- 7804065
TI  - Urinary tract infection in children. Consider severity of abnormalities.

PMID- 7804066
TI  - Urinary tract infection in children. GPs may not use same criteria.

PMID- 7804067
TI  - Histopathology and medical laboratory scientific officers.

PMID- 7804068
TI  - Reiter's syndrome attributed to hepatitis B immunisation.

PMID- 7804069
TI  - Skin necrosis induced by streptokinase.

PMID- 7804070
TI  - Future of cancer registries.

PMID- 7804071
TI  - Hepatitis B immunisation and reactive arthritis.

PMID- 7804072
TI  - Cochrane Collaboration.

PMID- 7804073
TI  - Chronic fatigue syndrome and fibromyalgia.

PMID- 7804074
TI  - Transmission of tuberculosis by patients with HIV infection.

PMID- 7804075
TI  - Age limits on infertility treatment and adoption.

PMID- 7804076
TI  - Aircraft cabin pressure and parkinsonian symptoms.

PMID- 7804077
TI  - Number of psychiatric beds needed.

PMID- 7804078
TI  - Overseas adoption.

PMID- 7804079
TI  - Young people's advice clinic in reproductive health.

PMID- 7804080
TI  - Privatisation of NHS prescribing.

PMID- 7804081
TI  - Report of Advisory Council on the Misuse of Drugs: AIDS and drug misuse update.

PMID- 7804082
TI  - Conversation with Ove Ferno.

PMID- 7804083
TI  - A treatment system for combined psychiatric and addictive illness.
AB  - Patients with combined general psychiatric and addictive disorders are a major
      public health problem in the US, and are being increasingly recognized as such
      world-wide. The authors describe a model treatment system for such patients in
      one municipal hospital in New York. It is composed of three complementary units:
      a locked ward, a halfway house and a day program. Treatment is based on a peer
      leadership approach coupled with professional treatment, and provides multiple
      levels of care to address the needs of respective patients. Of 464 admissions
      evaluated and treated, most were from disadvantaged minorities, homeless and
      abusers of cocaine. All were admitted with acute psychiatric or perinatal
      presentations, and carried Axis I diagnoses in addition to their substance abuse.
      Clinical experience over 6 years is reviewed, suggesting the feasibility of
      reorganizing general hospital psychiatric services to address the needs of the
      dually diagnosed.

PMID- 7804084
TI  - Alcohol and depression in English and American lawyer disciplinary proceedings.
AB  - This paper gives a comparison of the approach of the US courts and of the
      Solicitor's Disciplinary Tribunal in England to disciplinary proceedings
      concerning lawyers suffering from alcohol dependence and/or depression. A richer
      case law in the USA indicates a more sophisticated approach, higher standards as
      to evidence and better support systems for lawyers in recovery. Useful lessons
      could be learned from the American experience and the experience of doctors and
      dentists by English lawyers.

PMID- 7804085
TI  - Evaluation of a mass media campaign on smoking and pregnancy.
AB  - Two surveys were conducted among pregnant women throughout England, before (n =
      625) and after (n = 607) a mass media campaign on smoking and pregnancy targeted
      at women aged 15-24 years, in the social grade C2DE. The majority of the post
      campaign sample recalled having seen at least one of the campaign's series of
      press advertisements. There was a significant increase among this sample in those
      considering smoking to be very dangerous to the unborn child, in those
      understanding the term passive smoking and in those considering passive smoking
      to be very dangerous. During the campaign there was a 14% increase in the number
      of calls to a cessation helpline from pregnant women. Over the campaign there
      were no significant changes in smoking prevalence and consumption among pregnant
      women or partners or in the numbers of partners offering suggestions to pregnant
      women about their smoking behaviour.

PMID- 7804086
TI  - Alcohol in the mass media and drinking by adolescents: a longitudinal study.
AB  - Data from a longitudinal study carried out in Dunedin, New Zealand, were used to
      investigate associations between alcohol consumption at age 18 years and alcohol
      related mass media communications recalled at ages 13 and 15 years. The
      respondents' recall of alcohol-related mass media material were categorized as:
      commercial alcohol advertising, alcohol moderation messages or the portrayal of
      alcohol in entertainment. An additional media variable was the number of hours
      spent watching television. Non-media variables, such as peer approval of
      drinking, living situation and occupation (all at age 18 years) were also
      included in the analyses. The period between the interviews at ages 13 and 15
      years saw an increase in the broadcast of commercial alcohol advertisements on
      television in New Zealand and this was reflected in an increase in the proportion
      of the mass media material recalled which was categorized as commercial
      advertising. At age 15 years television advertising, mostly for beer companies,
      was the predominant material recalled. No relationships were found between the
      commercial advertising and wine and spirits consumption, among either men or
      women, but young women who had watched more hours of television drank more
      wine/spirits. Among women there were two unexpected negative relationships
      between recall of alcohol in the media at age 13 years and beer consumption.
      However, among men there was a consistent positive relationship such that those
      who had recalled more alcohol advertisements at age 15 years drank larger
      quantities of beer at age 18 years.

PMID- 7804087
TI  - Parenting behavior of adolescent children of alcoholics.
AB  - We compared the parenting behavior of children of alcoholics (COAs) and non-COAs
      within a sample of adolescent mothers. COAs and their children showed dyadic
      behaviors that were less problematic than those of their peers on mother-child
      teaching interactions at 1 year of age, mother-child interactions during
      structured play at pre-school age and child attachment behavior at pre-school
      age. COAs reported feeling relatively more rejection as compared to love from the
      alcoholic parent, but this was not related to their own parenting scores. Similar
      to other research, COAs reported more historical life stress, more family
      disruption and more drug use compared to non-COAs, but these measures also were
      not related to parenting scores. These results suggest that, although adolescent
      mothers are at risk for parenting difficulties compared to adult mothers,
      adolescent COAs do not necessarily encounter more problems in parenting their own
      children compared to other adolescent mothers.

PMID- 7804088
TI  - The effect of parental alcohol problems on rates of adolescent psychiatric
      disorders.
AB  - The relationships between parental alcohol problems and risks of psychiatric
      disorders including substance abuse, conduct, attention deficit, mood and anxiety
      disorders were examined in a birth cohort of New Zealand children studied to the
      age of 15 years. This analysis showed that children exposed to alcoholic parents
      had risks of adolescent psychiatric disorders that were between 2.2 (95%
      Confidence Interval (CI) = 1.4; 3.3) to 3.9 (95% CI = 2.40; 6.0) times higher
      than children whose parents did not report alcohol problems. After adjustment for
      a range of confounding factors these associations tended to reduce but even after
      adjustment, children of alcoholic parents had rates of disorder that were between
      1.6 (95% CI = 1.1; 2.6) to 3.0 (95% CI = 1.8; 4.5) times higher than the
      offspring of parents who did not have alcohol problems. The analysis suggested
      approximately linear relationships between the extent of reported parental
      alcohol problems and risks of disorder. There was no evidence to suggest that, in
      general, males responded to parental alcohol problems in a way that differed from
      the response of females.

PMID- 7804089
TI  - Assessment of the alcohol withdrawal syndrome--validity and reliability of the
      translated and modified Clinical Institute Withdrawal Assessment for Alcohol
      scale (CIWA-A).
AB  - The alcohol withdrawal syndrome is a common phenomenon in psychiatric hospital
      care. Not only treatment strategies, but also the evaluation of the syndrome, are
      discussed controversially. The most widely used instrument is the Clinical
      Institute Withdrawal Assessment-Alcohol (CIWA-A) and the succeeding CIWA-Ar. We
      modified the CIWA-A and translated it into German. Validity and reliability of
      the modified and translated scale were analysed by several psychological tests as
      well as different somatic measures in 31 patients. The German version appears to
      be a valid and reliable instrument for the assessment of alcohol withdrawal
      syndrome useful for clinical routine as well as treatment trials.

PMID- 7804090
TI  - Mortality in men with drinking problems: a 20-year follow-up.
AB  - This study presents mortality data from a 20-year follow-up of 99 married men
      with drinking problems. Forty-four of the sample had died and death certificates
      were obtained on 43. Cause of death was classified according to the Ninth
      Revision of the International Classification of Diseases. Most of the mortality
      excess was in the 45-54 year age group. The observed/expected mortality ratio was
      3.64 for the group as a whole, 2.93 for the moderately dependent group and 4.41
      for the severely dependent group. The commonest causes of death were carcinoma of
      the bronchus and diseases of the circulatory system. Cause of death was analysed
      in terms of years of life lost. The number of years of life lost per death was
      highest for injury and poisoning. Only four of the 43 death certificates obtained
      mentioned "chronic alcoholism".

PMID- 7804092
TI  - Drug-related behavior change for HIV transmission among American injection drug
      users.
AB  - While high risk drug-related behaviors for human immunodeficiency virus (HIV)
      transmission among injection drug users (IDUs) are asserted to have declined over
      time in response to the AIDS epidemic, evidence from longitudinal cohorts has
      been sparse. In a cohort of 810 IDUs (442 seronegatives and 368 seropositives) in
      Baltimore, we identified drug-related risk behaviors at four consecutive semi
      annual visits. Using robust methods for repeated measurements and multiple
      logistic regression, we estimated the probabilities of maintaining and reducing
      risk behaviors according to HIV serostatus and time in the study. Seropositive
      participants were more likely to maintain lower risk behaviors, and behavior
      maintenance increased with time in study for both seronegative and seropositive
      IDUs. Greater risk reduction (towards non-use and not sharing injection
      equipment) was seen among seropositive IDUs, with behavior change occurring soon
      after enrollment in the study. While behavior changes have been reported, many
      active IDUs, especially those still at risk for acquiring HIV infection, have not
      adequately reduced their risk. Continuing prevention programs and efforts in
      vaccine development are imperative to reduce the risk of HIV infection among
      IDUs.

PMID- 7804093
TI  - The prevalence of drug use in urban aboriginal communities.
AB  - The use of both licit and illicit drugs has been identified as a major health
      issue for Australian Aborigines. However, data on the proportion of people who
      use such drugs is scant. This cross-sectional survey of a randomly selected
      sample of urban Aboriginal people provides information on the use of the drugs
      alcohol, tobacco, marijuana, cocaine, heroin as well as petrol sniffing. Overall,
      a significantly smaller proportion of Aboriginal people were found to be current
      alcohol drinkers compared to non-Aboriginal Australians. A larger proportion of
      these drinkers were, however, found to be drinking at levels that were hazardous
      to their health. A significantly greater proportion of people from the Aboriginal
      sample were also found to be smokers compared to their non-Aboriginal
      counterparts. An examination of the use of the illicit substances revealed that a
      greater proportion reported they had ever used marijuana, compared to the other
      substances. The findings are discussed in terms of their implications for the
      health of Aboriginal people.

PMID- 7804091
TI  - Death and survival in a cohort of heroin addicts from London clinics: a 22-year
      follow-up study.
AB  - Data are presented on the 43 people who died over a 22-year follow-up period of a
      cohort of 128 heroin addicts drawn in 1969 from the newly opened London clinics.
      The main causes of death were drug-related, with 18 deaths specifically
      determined as due to overdose, of which the great majority were among people
      being prescribed opiates at the time. The mortality rate was a mean of 1.84%
      annually, and the excess mortality ratio was 11.9. This excess was highest at the
      beginning and varied over the period of study, appearing higher at the opening of
      the clinics and again in the mid-1980s. No sex differences in mortality rates
      were demonstrated but the excess mortality was concentrated at younger ages. No
      prediction of the 85 survivors could be made on the basis of length of heroin use
      prior to study intake, nor on age at intake.

PMID- 7804094
TI  - [The effect of chemical mutagens on the chromatin properties of mouse
      spermatogenic cells].
AB  - The main components of chromatin (DNA and protamine-like proteins) were studied
      in the Dipin- and NMU-treated mouse spermatogenic cells using quantitative
      cytochemistry. Marked variation of DNA content and deficiency of the basic
      nuclear proteins have been shown in epididymal spermatozoa developed from cells,
      which were at the moment of treatment either at the early prophase I or at
      intermediate stages of spermiogenesis. These stages are, respectively, one of
      genetically most sensitive stages and a stage of active synthesis of
      spermiospecific proteins, which play an important role in condensation and
      stabilization of gamete chromatin. The combined use of DNAse I and Feulgen
      reaction allowed us to obtain new data about cytochemical properties of chromatin
      in the other types of mouse germ cells after treatment with chemical mutagens.

PMID- 7804095
TI  - [The macromolecular factors of Ca2(+)-dependent cell adhesion in the liver].
AB  - Macromolecular adhesion factors have been obtained which differed from the
      previously obtained ones. They are acidic glycoconjugates with the molecular mass
      about 20-40 kD, which are capable of forming macromolecular aggregates and are
      located in the periphery of cell surface. After subdivision and purification of
      the mouse liver extract two-adhesion-active fractions were isolated, which
      changes the viscous-elastic properties of the liver tissue at extra low
      concentrations: 10(-13)-10(-17) M.

PMID- 7804096
TI  - [The sensitivity of tumor cells to low doses of antitumor preparations].
AB  - The anticancer activity of water solutions of nitrosomethylurea, adriblastin and
      cisplatin at low and extra low concentrations (to 10(-15) M) was studied in the
      mice with experimentally induced tumor. Single and multiple administration of
      these drugs at extra low doses changed the life duration. Nitrosomethylurea (10(
      15) M) increased the life duration by 20-86%. Nitrosomethylurea at extra low
      concentrations modifies the organism and tumor sensitivity to subsequent action
      of a high dose of this drug.

PMID- 7804097
TI  - [Cell growth and motility in culture (in vitro) under microgravity conditions.
      The Fibroblast Experiment].
AB  - The experiment "Fibroblast" was performed in 1992 on biosatellite "Cosmos-2229"
      in onboard device "Biobox" designed by the order of European Space Agency. The
      main objective was elucidation of the mechanisms responsible for the effect of
      space flight factors, mostly microgravity, on cell culture. We studied time
      related changes in growth, motility and some morphological characteristics of the
      cells in monolayer cultures on a solid substrate and in three-dimensional
      cultures supported by sponge gels. Studies were carried out on connective tissue
      cells isolated from the mouse embryos. Comparative after-flight analysis of the
      cell cultures exposed to space flight and of those under the normal gravity
      conditions (1 g) on the Earth has revealed some differences. The space flight
      conditions, mainly microgravity, induced marked changes in morphological
      characteristics and functional activity of the cultured fibroblasts: changes in
      the nucleus size and shape, retardation of cell growth and division rate. We
      believe that these changes may be due to weakening of intercellular contacts and
      cell adhesion to the substrate. These findings are important both for general
      biology and space medicine, specifically for the problems of tissue regeneration
      and wound healing under the conditions of long-term space flight.

PMID- 7804099
TI  - [Genetic defects in inheritance and the variability of locus Ldh-B in hybrid
      populations of Rana esculenta complex (Amphibia, Ranidae)].
AB  - The directed ingression of Lhd-B gene from R. lessonae to R. ridibunda observed
      during hybridization between these species was confirmed in the present study.
      The ingression was accompanied by decreased of the initial allele activity,
      segregative disturbances in heterozygotes and changes in electrophoretic
      mobility. The population genetic analysis has shown stable preservation of
      abnormal alleles in hybrid populations. The results are discussed with reference
      to the concept of genetic instability, its application to speciation models, and
      the neutralist vs. adaptationist controversy. Our data supports the neutral
      concept of allozyme variation.

PMID- 7804098
TI  - [The presence of mtDNA-like sequences in the DNA of liver chromatin fractions
      from rats of different ages].
AB  - We have used young (2-3 months), adult (6-8 months) and old (26-28 months) rats.
      Nuclear DNA (nDNA) was isolated from the liver nuclei and chromatin fractions
      (RCh, repressed chromatin; ACh, transcriptionally active chromatin; MCh, membrane
      bound chromatin) and thereafter loaded on nitrocellulose filters. Hybridization
      was carried out with radioactively labelled mitochondrial DNA (mtDNA) as a probe
      mtDNA was first isolated from the liver mitochondria of adult rats and then
      labelled in nick-translation reaction with 32P-dCTP. Radioautography densitometry
      data have shown that the content of mtDNA-homologous sequences in the liver nDNA
      was decreased in adult rats (56%) and increased in the old ones (240%), as
      compared with the young animals. mtDNA-homologous sequences were localized in the
      young rats mainly in the RCh, while the adult and old rats had similar sequences
      in the ACh. We suggest that the age-related dynamics of mtDNA-homologous
      sequences was due to various factors. At the early stages cell differentiation
      proceeds rapidly and is accompanied by structural and functional reorganization
      of both nuclear and mitochondrial genomes. These changes increase the probability
      of contacts and integration of mtDNA fragments and whole molecules in the nuclear
      genome. As a result, an elevated level of mtDNA-homologous sequences is observed
      in the liver nuclear genome of young rats. In adult rats, repair and elimination
      of cells with defective nDNA and decreased proliferation of hepatocytes account
      for decreased amounts of mtDNA-homologous sequences in nDNA. In old animals, the
      repair to destruction ratio shifts towards destruction and, hence, mtDNA
      homologous sequences are accumulated in the liver nDNA. Age related dynamics of
      mtDNA-homologous sequences in the liver chromatin fractions is characterized by
      accumulation of these sequences in ACh and MCh chromatin fractions during
      maturation and ageing. This also confirms our suggestion that integration of
      mtDNA-homologous sequences in the nuclear genome is due to various mechanisms
      operational at the early and late stages of ontogenesis.

PMID- 7804100
TI  - [The participation of vaginal bacteria in Phodopus campbelli in the chemical
      communication between male and female].
AB  - Phodopus campbelli commonly occurs in dry steppe and semidesert zone of south
      Siberia, Mongolia and China. Using radiotelemetry we found that a male has to
      cover about 2 km from his burrow to encounter a receptive female. Female in
      estrus marks a small area around its burrow by vaginal smear. Experiments were
      carried out in laboratory to discover the nature of this strong signal. In a
      "open field" area four boxes within stimuli we recorded the time complemented
      spent by males near boxes to study the attractive effect of intact receptive
      female, germ culture of vaginal smear and artificial mixed culture of bacteria
      which were found in the vaginal smear of Ph. campbelli receptive female. Males (n
      = 15) spent significantly more time near the boxes with female in estrus or day
      before estrus as compared with two other days of cycle. Germ culture from vaginal
      smear sampled on the estrus day was more attractive to males on 6th day than on
      the 2, -3, -5, -7, -8--or 9th days of cultivation, pure culture or germ culture
      sampled on anestrus. Mixed culture, which simulated the proportion of predominant
      bacteria in the estrus vaginal smear, was significantly more attractive for males
      on the 3rd day of cultivation. Thus sexual attractant of Ph. campbelli could be
      produced by some bacteria located in the vagina in estrus and it takes a couple
      of days of cultivation for maximum attractive effect.

PMID- 7804102
TI  - [Critical levels in the numerical growth of the world's population].
AB  - A critical level of the world human population growth, at which there will be a
      change in the growth tendency, was estimated on the basis of the available data
      on the world human population growth and the theory of critical levels in
      development (Zhirmunskii and Kuz'min, 1990). The critical value (N1) estimated
      from the world population 7,400,000,000 will be reached in 2003. However, when
      estimated on the basis of total biomass of human population (N2, seem less
      accurate), it will be reached in 2008, when the total numbers attain
      9,100,000,000.

PMID- 7804101
TI  - [Cytochemical evidence for endogenous hydrogen peroxide generation in the
      neutrophils from human blood smears].
AB  - We present more accurate evidence for generation of endogenous hydrogen peroxide
      as a result of peroxidase-endogenous hydrogen peroxide system activity in the
      neutrophils (Rogovin et al., 1978). The normal cytochemical reaction of the
      peroxidase-endogenous hydrogen peroxide system in the neutrophil peroxidasosomes
      after elimination of water-dissolved H2O2 by KMnO4 indicates the neutrophils on
      smears as a source of H2O2, rather than alcohol-formaldehyde. This is confirmed
      by the cytochemical reaction of peroxidase-endogenous H2O2 reaction in the
      neutrophils on smears prepared without fixation. The peroxidase-endogenous H2O2
      system in the neutrophils on blood smears acts at pH other than peroxidase: 7.7
      5.5 vs. 7.7-3.4 (basic pH range was not examined). This difference appear to be
      due specific features of the enzyme complexes ultimately generating H2O2.

PMID- 7804103
TI  - Black diaphragm intraocular lens in congenital aniridia.
AB  - Beginning in June 1991, we implanted a newly designed, black diaphragm
      intraocular lens (IOL) into 13 eyes with congenital aniridia after cataract
      surgery. To the best of our knowledge, this is the first group of patients to
      receive a black diaphragm IOL. With the first prototype we experienced various
      difficulties, which prompted four design modifications. The latest IOL with a
      diaphragm diameter of 10 mm can be guided safely into the ciliary sulcus. IOL
      implantation improved visual acuity in 9 of 13 eyes; 4 of these exhibited
      considerably less nystagmus than was observed preoperatively. During the mean
      follow-up-period of 7.9 months (range, 1-27 months), a slight, persistent
      intraocular "inflammation" [Tyndall (+)] was observed in all eyes. Glaucoma
      occurred postoperatively in 4 eyes and was controlled medically in 2 eyes but
      remained uncontrolled in 2 other eyes that had the condition preoperatively. This
      pilot study indicates that most patients with congenital aniridia and cataract
      benefit considerably from the implantation of this newly designed, black
      diaphragm IOL. However, preexisting glaucoma may herald severe postoperative
      glaucoma-related problems and should be considered a contraindication until more
      information has been gained about the long-term tolerance of this IOL.

PMID- 7804104
TI  - Optical and thermal mechanisms related to the design of laser sclerostomy.
AB  - Collateral, thermally induced structural damage during laser sclerostomy ab
      interno or ab externo was investigated theoretically and compared with
      experimental results. We show that collateral heat damage in contact strategies
      using fiber delivery is mainly due to heat conductivity following explosive
      ablation. Electron micrographs of perforated porcine eyes show that the damage is
      only weakly dependent on the laser wavelength. The experiments also demonstrate
      that simultaneous application of laser irradiation and pressure with the fiber
      tip yield efficient perforation of scleral tissue even when the weakly absorbed
      radiation of Nd:YAG or diode lasers is employed.

PMID- 7804105
TI  - Contact diode laser cyclo-photocoagulation for refractory glaucoma. A pilot
      study.
AB  - Initial experience with non-contact diode cyclo-photocoagulation for refractory
      glaucoma has shown positive results. Diode laser irradiation applied via a
      contact probe results in greater transmission through the sclera and delivery of
      more energy to the ciliary body. A trial was performed to evaluate the effects of
      contact diode cyclo-photocoagulation. A total of 12 patients with glaucoma due to
      conditions such as central retinal vein occlusion were treated. A mean of 22
      pulses (810 nm) with powers of up to 2 W and of 2 s duration were applied via a
      fibre-optic delivery system and a contact probe. The mean intra-ocular pressure
      dropped from 42.3 to 13.6 mmHg over 3 months. Four patients required retreatment.
      Three patients had side effects that included hyphaema, anterior fibrinous
      uveitis and pupil block. In conclusion, contact diode cyclo-photocoagulation had
      a significant ocular hypotensive action in the treatment of refractory glaucoma.
      As compared with non-contact diode cyclo-photocoagulation, the contact modality
      produced more marked non-therapeutic side effects.

PMID- 7804106
TI  - Reproducibility and intraindividual variability of the pattern electroretinogram.
AB  - The human pattern electroretinogram (PERG) is a contrast-specific potential
      presumedly reflecting the functional integrity of ganglion cells. Many studies
      have devised criteria that enable PERG measurements to distinguish established
      glaucomatous (hypertonic) eyes from normal controls. As there are relatively few
      reports concerning the reproducibility and reliability of the PERG, we studied
      the intraindividual variability of the PERG in 20 healthy subjects. Both
      transient and steady-state responses were recorded using a high-contrast (98%),
      black-and-white, counterphasing checkerboard pattern (average luminance, 80
      cd/m2) generated by a television monitor (subtending angle, 13.8 degrees x 10.8
      degrees) using three different check sizes (15', 30', and 60'). Recordings were
      performed in both eyes simultaneously at a 7-day interval under test-retest
      conditions. Responses of 30' spatial frequency were most consistent and resulted
      in a mean amplitude (+/- SD) of 2.18 +/- 0.95 microV (P50) and 4.00 +/- 1.69
      microV (N95) for transient patterns and 1.84 +/- 1.25 microV for steady-state
      patterns. No statistically significant difference was observed between either
      right and left eyes, test and retest conditions or 1st- and 7th-day recording
      sessions for PERG parameters. In linear correlation analysis there was an
      adequate, positive correlation between the right and left eyes (r = 0.78); a weak
      correlation between test and retest conditions (r = 0.58); and no correlation
      between measurements made at a 7-day interval. As a consequence, we conclude that
      the follow-up of patients (e.g., glaucoma, ocular hypertension) by means of PERG
      is critical, especially when therapeutic consequences may be based on the
      physiological variability of a weak retinal signal.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7804107
TI  - Asymmetries in texture perception.
AB  - Single elements in textures segregate preattentively from the background if they
      differ in special features from surrounding elements (pop-out). Oblique targets
      on a background of vertical line elements are more easily detected than vertical
      targets on a ground of oblique elements. We wanted to find out whether this
      perceptional asymmetry depends on the absolute orientation or on the alignment of
      the background lines. Using the method of constant stimuli, we measured the
      thresholds of detection times in five subjects using four different arrangements
      of line patterns. The subjects indicated the position of a salient element in a
      forced-choice procedure. For all subjects, detection times were shortest if
      background lines were either vertical or collinear. Otherwise, detection times
      were significantly longer by a factor of 3. Figure-ground segregation is
      facilitated if background lines are either vertical or collinear.

PMID- 7804108
TI  - Bilateral uveal melanoma presenting simultaneously.
AB  - A case of bilateral uveal melanoma in a 54-year-old man is described. On
      admission of the patient for a choroidal melanoma of the left eye, an
      asymptomatic ciliary-body tumour was detected in his right eye. A thorough
      general examination did not reveal any metastases. The left eye was enucleated
      and local excision of the tumour in the right eye was performed 2 months later.
      Histology confirmed the presence of malignant melanomas in both eyes. The tumours
      were of similar A/B spindle-cell type. The patient remained healthy, showing no
      sign of metastasis or local recurrence of melanoma 9 months after the date of
      diagnosis. The visual acuity in his remaining eye remained 6/6. Immunological
      assessment of the blood serum revealed abnormally high interleukin 1 beta (IL-1
      beta) and IL-2 levels. Possible implications of these findings are discussed.

PMID- 7804109
TI  - Histopathologic findings in large uveal melanomas after brachytherapy with iodine
      125 ophthalmic plaques.
AB  - Eyes of 25 patients among a series of 100 consecutive patients who underwent
      iodine 125 brachytherapy for extremely large uveal melanomas measuring more than
      7-8 mm in height had to be enucleated after an average interval of 1.4 years. The
      dose delivered to the tumor apex was 120-150 Gy. Indications for enucleation were
      most frequently radiation-induced alterations in the anterior segment with loss
      of fundus visibility. Eight cases showed insufficient tumor regression, and two
      cases were suspicious for growth. Microscopically complete tumor necrosis was
      found in ten eyes. Six cases were classified as "uncertain tumor regression."
      Apparently "viable" tumor cells were seen in nine eyes. This group of eyes showed
      a significantly shorter interval between therapy and enucleation. One specimen
      showed extraocular tumor extension. Brachytherapy with iodine 125 may result in
      complete tumor necrosis, even in large uveal melanomas. The morphologic extent of
      tumor necrosis seems to be positively correlated with the interval after therapy.

PMID- 7804110
TI  - Is general anaesthesia necessary to record reproducible electroretinograms in
      rabbits?
AB  - In toxicity testing of intraocularly applied substances the flash
      electroretinogram (ERG) serves as an indicator of intact or reduced retinal
      function in the animal. Insufficiently monitored narcosis may be a source of
      puzzling ERG results. We performed electroretinography in 25 dark-adapted rabbits
      without general anaesthesia to evaluate the reproducibility of that method. Two
      recordings obtained at a mean interval of 26.87 days were compared. The scotopic
      a- and b-waves showed the same characteristics concerning shape, amplitude and
      implicit time known from other publications dealing with ERG recordings in
      narcotised rabbits. No statistically significant difference could be found
      between the test and retest recordings. It could be demonstrated that narcosis is
      not necessary for recording of stable and reproducible scotopic ERGs in rabbits.

PMID- 7804111
TI  - Different concentrations of vasoactive intestinal polypeptide in aqueous humor of
      patients with proliferative vitreoretinopathy and cataract patients.
AB  - The pathophysiological events leading to cellular proliferation in proliferative
      vitreoretinopathy are largely unknown. An involvement of neuropeptides in that
      disease has recently been discussed, as substance P was found to be highly
      enriched in the intraocular fluid of patients with proliferative
      vitreoretinopathy. In the present study, aqueous humor was analyzed for another
      neuropeptide, vasoactive intestinal polypeptide. Radioimmunoassay revealed
      significantly increased levels of that polypeptide in the aqueous humor of
      patients with proliferative vitreoretinopathy as compared with cataract patients
      who served as controls. As vasoactive intestinal polypeptide contributes to the
      environment of the retinal pigment epithelial cell layer and induces
      proliferation of these cells in vitro, this peptide may be involved in the
      pathogenetic mechanisms leading to cellular proliferation in proliferative
      vitreoretinopathy.

PMID- 7804112
TI  - Natriuretic peptides and their receptors in human neural retina and retinal
      pigment epithelium.
AB  - Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) play a role
      in transepithelial fluid movement in the kidney and at the blood-aqueous barrier.
      We sought a similar natriuretic peptide-mediated regulatory system at the level
      of the blood-retinal barrier by investigating human neural retina and retinal
      pigment epithelium for the presence of ANP, BNP and their receptors. ANP and BNP
      binding to receptors could be demonstrated autoradiographically in all layers of
      the retina inclusive of the retinal pigment epithelium. Competitive preincubation
      with unlabeled peptides blocked the binding of the respective radioactive
      peptide. ANP and BNP could also be demonstrated immunohistochemically in both the
      neural retina and the retinal pigment epithelium. Our results suggest a role of
      these peptides both in the regulation of intraretinal fluid movement and--by
      analogy with other peptides--as possible neutrotransmittors. The localisation of
      ANP and BNP in the retinal pigment epithelium suggests that these peptides may
      influence ocular fluid homeostasis at the outer blood-retinal barrier by
      modulating pigment epithelial function.

PMID- 7804113
TI  - Tight junctions of the human corneal endothelium: morphological and
      electrophysiological features.
AB  - The corneal endothelium controls the hydration and nutrition of the avascular
      corneal stroma. To analyze the role of the tight junctions (TJ) for these
      functions, we examined human corneal endothelium by thin-section and freeze
      fracture electron microscopy and by impedance analysis. On thin sections, tannic
      acid was seen to mark the external leaflet of the lateral plasma membrane also
      beyond the location of the TJ, indicating a significant macromolecular porosity
      of the TJ. On freeze-fracture images, the TJ surrounded the entire apicolateral
      plasma membrane but were found to be focally incomplete, suggesting a
      nonhomogeneous seal of the lateral intercellular space. Impedance analysis
      revealed a very leaky endothelial layer with a transendothelial resistance of 9.0
      +/- 1.4 omega cm2. These findings are consistent with the hypothesized "pump
      leak" model of the corneal endothelium: the TJ allow an effective dehydration of
      the corneal stroma, whereas the interruptions in the TJ network may be the
      morphological correlate for the passage of nutrients into the corneal stroma. Our
      data corroborate the assignment of the corneal endothelium to the group of "very
      leaky epithelia" that exhibit high transport rates of water and solutes against
      only minimal osmotic gradients.

PMID- 7804114
TI  - Study of the retinal fiber layer in patients with acquired immunodeficiency
      syndrome.

PMID- 7804115
TI  - Progressive nursing-psychological care interventions.

PMID- 7804116
TI  - Validity of concepts for selected nursing diagnoses.
AB  - The purpose of this study was to determine the extent to which defining
      characteristics found in selected patients cluster to form a nursing diagnostic
      response/label or define a concept, and to determine the construct validity of
      the defining characteristics for Self-Care Deficit, Impaired Mobility, and Pain.
      The sample included 309 medical-surgical patients who were found to have the
      diagnostic responses of interest. The signs and symptoms of the 309 patients were
      submitted to cluster analysis. Scores on the clusters were examined for their
      ability to differentiate between two known groups of patients: those identified
      by clinical nurse specialists (CNS) as having, or not having, selected diagnostic
      responses/labels. The cluster score Self-Care Deficit differentiated between
      patients with and without the CNS-diagnostic response of Self-Care Deficit and
      Pain. Patients with CNS-diagnosis of Self-Care Deficit and Impaired Mobility
      scored high in the Impaired Mobility Cluster score. Limitations of the study,
      clinical relevance, and recommendations for future research are discussed.

PMID- 7804117
TI  - Recommendations by clinicians for nausea and vomiting of pregnancy.
AB  - The purpose of this study was to assess both the current use of relief measures
      for nausea and vomiting of pregnancy among clinicians and the basis for their
      decisions regarding method of treatment. With the permission of conference
      sponsors, questionnaires on nausea and vomiting of pregnancy relief measures were
      distributed at a national conference for obstetrical health care providers. Of
      the 600 conference participants, 130 completed questionnaires. The findings of
      the study indicate that clinicians generally recommend eating small, frequent
      meals; that clinicians modify their recommendations slightly based on the
      severity of the symptoms; that clinicians perceive varying degrees of
      effectiveness of relief measures, with no one measure being totally effective;
      and that clinicians look to patients as the primary resource for information
      about nausea and vomiting of pregnancy.

PMID- 7804118
TI  - The Alcoholism Denial Assessment Tool (ADAT): a study of interrater reliability.
AB  - The purpose of this study was to develop and test a tool for assessing alcoholic
      denial. The primary author devised the Alcoholism Denial Assessment Tool (ADAT)
      based on 2 years of experience. The tool was tested for interrater reliability
      using chart data of 42 recently discharged alcoholism patients. The test for
      significance of a proportion, using z scores, indicated significance at the .001
      level. Item analysis showed strong interrater reliability on all but 1 of the 16
      tool items. The ADAT provides nurses with a practical assessment tool that can be
      used daily to monitor progress. Recognition that a patient is in denial can allow
      meaningful and appropriately planned treatment.

PMID- 7804119
TI  - Cardiac patients and spouses: family functioning and emotions.
AB  - This study examined the relationships among satisfaction with family function and
      emotional states of a nonprobability sample of sixty-six myocardial infarction
      (MI) patients and their spouses who were recruited from hospitals in the Delaware
      Valley. Patients and spouses completed the Family APGAR and the Affects Balance
      Scale. It was found that both patients and spouses experienced substantial
      emotional distress when compared with the norms for nonclinical subjects. They
      were highly correlated on both measures, particularly for positive emotion and
      satisfaction with family function (p < .0001). Satisfaction with family function
      was significantly correlated with positive affect for spouses (p < .05). These
      results suggest the importance of assessment of satisfaction with family function
      and emotional status of both MI patient and spouse, with spouses with lower
      satisfaction with family function being at greater risk for emotional distress.

PMID- 7804120
TI  - Understanding depression in bereaved older adults.
AB  - Depression is a common outcome of spousal bereavement. Concurrent life events may
      contribute to the intensity of depression following spousal bereavement in older
      adults and, if not identified, may interfere with therapeutic plans for the
      management of depression. Taped interviews, conducted six times over two years,
      were analyzed for ten subjects, five whose depression scores were low, and five
      whose scores were high. In addition, a detailed case comparison analysis of two
      subjects was done. Four recurring types of life events, reported by the bereaved
      spouses, were illness (of self or others), deaths of family or friends,
      residential relocation, and changes in interpersonal relationships. Significantly
      depressed spouses were more likely to report these events. Implications for
      nursing practice and for integrating qualitative and quantitative research
      methods are addressed.

PMID- 7804121
TI  - Factors influencing nursing home placement decisions: the older adult's
      perspective.
AB  - The study used a qualitative design to describe the decision making involved when
      an older adult relocated to a nursing home. Tape recorded semistructured
      interviews were conducted with 18 nursing home residents. Findings indicate that
      the decision to relocate the older adults to the nursing home was commonly made
      by their physician in response to acute and chronic health problems. Subjects
      described their residential preferences, discussed problems encountered after
      nursing home placement, and gave advice to other older adults contemplating
      relocation to a nursing home. Nursing interventions could be directed toward
      community residential alternatives and advocacy to ensure the older adult's
      involvement in the decision making as much as is possible.

PMID- 7804122
TI  - The activation antigen CD69.
AB  - One of the earliest cell surface antigens expressed by T cells following
      activation is CD69, which is detectable within one h of ligation of the T cell
      receptor/CD3 complex. Once expressed, CD69 acts as a costimulatory molecule for T
      cell activation and proliferation. In addition to mature T cells, CD69 is
      inducibly expressed by immature thymocytes, B cells, natural killer (NK) cells,
      monocytes, neutrophils and eosinophils, and is constitutively expressed by mature
      thymocytes and platelets. Recently, cDNA clones encoding human and mouse CD69
      were isolated and showed CD69 to be a member of the C-type lectin superfamily.
      Gene mapping studies have placed CD69 on distal mouse chromosome 6 and human
      chromosome 12p13, close to, if not in, the NK gene complex. The structure,
      chromosomal localization, expression and function of CD69 suggest that it is
      likely a pleiotropic immune regulator, potentially important not only in NK cell
      function but also in the activation and differentiation of a wide variety of
      hematopoietic cells.

PMID- 7804123
TI  - Intensive therapy and autotransplantation in Hodgkin's disease.
AB  - Intensive therapy and autologous marrow or peripheral blood stem cell
      transplantation is often utilized in Hodgkin's disease patients whose disease has
      progressed after primary conventional chemotherapy. A number of studies have
      described long-term disease-free survival in up to 50% of transplanted patients.
      High-dose chemotherapy conditioning regimens such as "CBV" or "BEAM" have been
      used more often than regimens containing total body irradiation. Usually unpurged
      autologous bone marrow has been utilized as the source of hematopoietic stem cell
      reconstitution, although recently the use of "primed" peripheral blood stem cells
      has increased markedly. The challenges of transplant-related toxicity and
      recurrence of disease post-transplant are discussed, as well as possible
      strategies to reduce these problems. The use of autologous transplantation is
      discussed in three clinical settings: patients who have failed to enter a
      complete remission (CR) after primary chemotherapy, those who have relapsed
      within 12 months of attaining a CR and those who have relapsed after a longer
      (i.e., > or = 12 months) first CR. When compared with conventional salvage
      chemotherapy, transplantation appears to produce a higher long-term disease-free
      survival rate in all of these patient groups. However, assessment of an advantage
      for autotransplantation, particularly in patients with long first remissions, is
      difficult without a Phase III trial. On the other hand, recently updated results
      from our center indicate that 72% of patients relapsing after long initial
      remissions benefit from autotransplantation at this point in their disease
      course, and that transplant-related mortality is low in this setting. Other
      issues addressed include the potential role of autologous transplantation as
      consolidation therapy in selected high-risk patients in an initial CR, as well as
      the utility of conventional chemotherapy and involved-field radiotherapy in
      conjunction with autotransplantation.

PMID- 7804124
TI  - Erythropoietin increases the radioresistance of a clonal hematopoietic progenitor
      cell line expressing a transgene for the erythropoietin receptor.
AB  - Erythropoietin (Epo) is a serum glycoprotein growth factor required for the
      survival, proliferation and differentiation of committed erythroid progenitor
      cells. In the present study, we sought to determine whether the action of Epo via
      its receptor is also implicated in the repair of radiation-induced cell damage.
      Overexpression of the Epo receptor (Epo-R) was achieved as a result of
      transfection of the 32D cl 3 clonal hematopoietic cell line. These clonal lines
      allowed us to investigate the effects of Epo on the radiation sensitivity in
      vitro of a clonal murine hematopoietic progenitor cell line. Low level expression
      of Epo-R on many hematopoietic cell types was thus circumvented. Ligand binding
      of Epo resulted in increased radioresistance of 32D cl 3 subclonal lines
      expressing the Epo-R transgene. The D0 of 32D Epo-R cells at 1.49 Gy/min was 1.33
      Gy and n was 1.39. The D0 of parental clonal cell line 32D cl 3 cells at 1.49
      Gy/min was 1.36 Gy and n was 1.39. In contrast, at the low dose rate of 0.0595
      Gy/min, the D0 of 32D Epo-R cells was 2.0 Gy and n was 1.24, while parental
      clonal line 32D cl 3 showed a D0 of 1.35 Gy and n was 1.39. The increased
      radioresistance was statistically significant at low dose rate (p < 0.05).
      Combined exposure to Epo and interleukin 3 (IL-3) increased proliferation of 32D
      Epo-R cells but did not induce a detectable further increase in radioresistance.
      Temporal dissociation between growth factor-activated tyrosine phosphorylation of
      intracellular substrates, and the radioprotective effect was observed.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7804127
TI  - Effects of ozone on the activity of erythrocyte membrane Na(+)-K+ ATPase.
AB  - Ozone (5 mumol.min-1) inhibited the human erythrocyte membrane Na(+)-K+ ATPase
      (EC.3.6.1.39) activity in a time dependent manner. Inhibition was more pronounced
      for the first 5 min of ozone exposure in the directly ozone exposed membranes
      than in the membranes prepared from ozone exposed erythrocytes. However, Na(+)-K+
      ATPase activities of both preparations were inhibited to the same extent (about
      70%) at the end of 10 min ozone exposure. It was also determined that there was a
      close relationship between the decrease of enzyme activity and the increase in
      the thiobarbituric acid reactive substances in both types of preparations. Na(+)
      K+ ATPase was inhibited by ozone even at the presence of vitamin E or vitamin C.
      However, the degree of the inhibitions and the amounts of thiobarbituric acid
      reactive products formed were smaller than the corresponding values found in the
      absence of these vitamins.

PMID- 7804126
TI  - Comparative heat sensitivity of murine and human hemopoietic progenitors and
      clonogenic leukemia cells.
AB  - The aim of this study was to compare the thermal sensitivity of normal murine and
      human hemopoietic progenitors to that of leukemic murine and human clonogenic
      cells in order to assess the clinical relevance of experimental data. Colony
      forming units-granulocyte-macrophage (CFU-GM) from normal human bone marrow and
      from bone marrow of patients with acute lymphocytic leukemia (ALL), acute
      myelogenous leukemia (AML), and Hodgkin's disease in complete remission proved to
      be less sensitive to 42.5 degrees C in vitro hyperthermia (D0: 93.9 min) than
      murine bone marrow CFU-GM (D0: 49.6 min). Leukemic colony forming cells (CFU-L)
      from HL-60 suspension culture--when compared to human CFU-GM--showed
      significantly increased thermal sensitivity (D0: 22.8 min). While the thermal
      sensitivity of CFU-L from a murine leukemia cell line (WEHI 3-B) was not
      statistically significant when compared to that of CFU-L from HL-60 (D0 values
      17.0 versus 22.8 min), the vertical difference between the parallel regression
      lines suggested an approximately three-fold greater survival for human CFU-L.
      Although carefully controlled hyperthermia is an easy purging technique, the
      relevance of murine data to human clinical practice must be considered
      critically.

PMID- 7804125
TI  - Transforming growth factor-beta 1 augments macrophage-colony stimulating factor
      activity on human marrow.
AB  - Transforming growth factor-beta 1 (TGF-beta 1) suppresses the colony stimulating
      activity of most cytokines. The effect of TGF-beta 1 on macrophage colonies
      induced by macrophage colony stimulating factor (M-CSF) from human marrow has not
      been described. Experiments were performed with phenylalanine methyl ester (PME)
      treated marrow. PME (5 mM) eliminates stromal cells and monocytes. Colony
      stimulatory factors were used at plateau concentrations. TGF-beta 1 (0.1 ng/ml)
      significantly (p < 0.05) augmented M-CSF induced macrophage colony forming units
      (CFU-M) by twofold to fourfold in 8/8 donors. In contrast, colonies stimulated by
      granulocyte-macrophage CSF (GM-CSF) (CFU-GM), were significantly decreased by TGF
      beta 1. To determine if TGF-beta 1 was present in effective concentrations in
      vitro, cultures were performed with anti-TGF-beta 1. Anti-TGF-beta 1 decreased (p
      < 0.05) M-CSF induced colonies in 5/6 donors. The method of TGF-beta 1
      enhancement was explored with antihuman CSF-1 receptor antibody. Antihuman CSF-1
      receptor antibody resulted in comparable suppression of CFU-M resulting from both
      M-CSF and M-CSF + TGF-beta 1. These studies indicate that TGF-beta 1 directly
      enhances M-CSF activity by a mechanism other than upregulation of M-CSF
      receptors.

PMID- 7804129
TI  - Intra-A chain disulfide bond (A6-11) of insulin is essential for displaying its
      activity.
AB  - The mutant proinsulin gene was constructed with the codons for A6 and A11 Cys
      changed to Ser to delete intra-A chain disulfide bond. After expression and
      purification, the mutations in the protein were further confirmed by amino acid
      composition. Electrophoretic mobility of the mutant proinsulin is similar to that
      of human proinsulin, so are the products of tryptic digestions. The mutant
      proinsulin, which retains its full radioimmuno activity, shows only 5.4% of
      receptor binding activity of human proinsulin. This suggests that though the
      intra-A chain disulfide bond disappears, the other two inter-chain disulfide
      bonds are still correctly paired, and hence the three dimensional structure has
      not been altered significantly. This intra-chain disulfide bond is essential for
      insulin displaying its activity.

PMID- 7804128
TI  - Synthesis of new oligopeptides and their scavenging abilities against active
      oxygen species.
AB  - The reactivities of new synthetic oligopeptides containing cysteine or histidine
      towards active oxygen species such as superoxide (O2-) and hydroxyl radical (.OH)
      were investigated by an electron spin resonance (ESR)-spin trapping method. At
      physiological pH values, these oligopeptides greatly suppressed the generation of
      .OH from the reaction of Cu(en)2 (en: ethylenediamine) with hydrogen peroxide
      (H2O2), although these oligopeptides did not scavenge O2-. The antioxidant
      mechanism of these oligopeptides is discussed.

PMID- 7804130
TI  - A mitochondrial tRNA(Leu)(UUR) mutation at 3,256 associated with mitochondrial
      myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS).
AB  - Enzymatic and molecular analyses were conducted on the muscular tissue of a
      patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke
      like episodes (MELAS). Significant decreases in activity of complexes I and IV
      were found and three nucleotide substitutions in the mitochondrial tRNA genes
      were detected. Two of the substitutions were detected in unaffected members of
      the family and in some healthy controls. A C-to-T transition mutation at the
      nucleotide position 3,256 in the mitochondrial tRNA(Leu)(UUR) gene was detected
      only in the patient and not in unaffected members of the family or 100 healthy
      controls. The data strongly suggest that this mutation at nucleotide position
      3,256 in the mitochondrial tRNA(Leu)(UUR) gene is associated with MELAS.

PMID- 7804132
TI  - Mixing rates can markedly affect the kinetics of peptide-induced leakage from
      liposomes.
AB  - Assays on vesicle aqueous content leakage are widely used in the study of peptide
      lipid interactions. We found this assay to be affected by the mode of mixing
      vesicle and peptide solutions. This effect can lead to artifactual conclusions
      regarding the lytic activity of peptides. We demonstrate that the source of this
      artifact is that fast (millisecond range) peptide-membrane association creates a
      nonhomogeneous distribution which exists sufficiently long after peptide addition
      to markedly alter the course of leakage. Mixing problems can be overcome by using
      a stopped flow apparatus. It can also be diminished by switching to injecting a
      small volume of vesicle suspension into a large volume of peptide solution.
      Mixing rates are rarely considered in literature reports of peptide effects on
      liposomes. The same artifacts can also take place in a number of other assays of
      the activity of membrane active peptides on liposomes and thus their
      consideration is of general importance.

PMID- 7804131
TI  - Effects of dehydroepiandrosterone and carnitine treatment on rat liver.
AB  - It is well established that DHEA treatment is associated in the rat to an
      increase in fatty acids metabolism. This condition would require levels of L
      carnitine much higher than those physiologically present in the liver. The
      possibility thus exist that during DHEA treatment the concentration of L
      carnitine may become a limiting factor for fatty acids oxidation and therefore
      responsible of some of the effects observed after administration of the hormone.
      The present experiments were designed to test this hypothesis. The results show
      that the increase in the levels of peroxisomal enzymes induced in hepatocytes by
      DHEA, is greatly reduced by parallel administration of L-carnitine. Furthermore,
      L-carnitine administration counteracts the effect of DHEA on mitochondrial
      structure. On the contrary, carnitine has no significant effect on the reduction
      in weight gain observed upon short- or long-term treatment with DHEA.

PMID- 7804133
TI  - Rapid purification of tRNA(Lys) from rat liver.
AB  - Fast protein liquid chromatography (FPLC) system using Mono Q (HR 5/5) anion
      exchange column chromatography followed by highly cross-linked urea
      polyacrylamide gel electrophoresis (urea-PAGE) was used for the purification of
      lysine-specific tRNA (tRNA(Lys)) from rat liver. Crude tRNA from rat liver was
      fractionated with a linear gradient of NaCl (0.3-0.8 M) in triethanolamine-HCl
      buffer, pH 4.5, and the activity of tRNA(Lys) was found to elute between 0.51 and
      0.57 M NaCl. Using this concentration range of NaCl, tRNA(Lys) was refractionated
      on the same column with a shallow gradient, where a single peak of tRNA(Lys)
      activity was obtained. tRNA(Lys)-rich fractions recovered from the second run
      were electrophoretically separated on 16% polyacrylamide-7 M urea gel into one
      major band and three minor bands. The major band showed a specific activity of
      997 pmols/A260 U for tRNALys with a 43-fold purification and approximately 17%
      recovery. The minor bands displayed negligible or no activity for lysine.
      tRNA(Lys) obtained by this method was found to be homogeneous by competitive
      aminoacylation. The advantages of FPLC followed by urea-PAGE in the purification
      of an amino acid-specific tRNA over conventional column chromatography are
      discussed.

PMID- 7804134
TI  - Brain ECTO-Mg-ATPase is not the neural cell adhesion molecule.
AB  - We have investigated the relationship between the ecto-Mg-ATPase and the neural
      cell adhesion molecule (NCAM) in brain. Rat and chicken brain microsomes were
      solubilized and the crude, soluble mixtures were partially purified by anion
      exchange chromatography. Chromatographic fractions were assayed for the presence
      of Mg-ATPase activity and the ATPase and NCAM proteins by Western blot analysis.
      In both rat and chicken brain, the Mg-ATPase was separated from the neural cell
      adhesion molecule on the anion exchanger. In addition, immunoprecipitation of
      solubilized rat brain microsomes with an anti-NCAM antibody did not precipitate
      any Mg-ATPase activity but did precipitate NCAM. We conclude that the brain ecto
      Mg-ATPase is neither identical to, nor closely associated with, the neural cell
      adhesion molecule, contrary to a previous report (Dzhangzhugazyan, K. and Bock,
      E. (1993) FEBS Lett. 336, 279-283).

PMID- 7804135
TI  - The human hepatoma cell line, HepG2, secretes functional cholinesterase.
AB  - Confluent monolayers of the human hepatoblastoma-derived cell line, HepG2, were
      incubated in serum-free medium. This medium was harvested and concentrated.
      Catalytic activity and immunoblotting of concentrated medium revealed the
      presence of a functional cholinesterase. This cell line may be an useful model
      for investigating the regulation and physiological role of the enzyme secreted by
      liver.

PMID- 7804136
TI  - Expression of all-trans-retinoic acid receptor RNA in human thyroid cells.
AB  - The expression of all-trans-retinoic acid receptor (RAR) RNA was investigated by
      Northern blot and Reverse Transcription-Polymerase Chain Reaction in tissues and
      primary cultures of human thyrocytes. In normal and adenomatous samples the RAR
      alpha RNA was expressed, whereas the expression of RAR beta and gamma was
      undetectable. In carcinoma samples RAR alpha RNA expression could decline,
      whereas the RAR beta RNA expression could become detectable. TSH and retinoic
      acid did not significantly modify RAR alpha mRNA levels, whereas RA caused a
      significant decrease in basal and TSH-induced thyroid peroxidase (TPO) mRNA
      levels, and a decrease in DNA synthesis. These results demonstrate that RAR alpha
      gene is predominantly expressed in human thyrocytes, and suggest a molecular link
      between this gene and the negative regulation by RA of proliferation and function
      of follicular cells.

PMID- 7804137
TI  - The prolactin of European sea bass (Dicentrarchus labrax L.): cloning of cDNA and
      efficient expression in Escherichia coli.
AB  - The cDNA encoding sea bass (Dicentrarchus labrax) prolactin (sbPRL) was obtained
      by reverse transcription-polymerase chain reaction (RT/PCR) from pituitary RNA
      with degenerate primers designed on the basis of the cDNAs of the two PRLs
      (tPRL188 and tPRL177) from the tilapia, Oreochromis niloticus. The sbPRL cDNA
      encodes a preprotein of 212 amino acids composed of a putative signal peptide of
      24 residues and a mature protein of 188 amino acids that is the homologue of
      tiPRL188. The cDNA coding for the mature protein was cloned into the pAX4a+
      expression vector and expressed efficiently in Escherichia coli as a beta
      galactosidase-fusion protein. To split the fusion protein, a sequence encoding
      the hexapeptide, (Asn-Gly)3, that contains three Asn-Gly hydroxylamine-cleavable
      bonds, had been previously introduced by PCR upstream of the sbPRL cDNA. N
      terminal sequencing confirmed that the cleaved product corresponded to sbPRL. An
      antiserum raised against the recombinant hormone detected by immunoblotting a
      single band in sea bass pituitaries and two bands in tilapia pituitaries,
      suggesting the occurrence of a single PRL form in sea bass.

PMID- 7804138
TI  - Hexose metabolism in pancreatic islets UDP-glucose pyrophosphorylase activity.
AB  - UDP-glucose pyrophosphorylase was measured in rat pancreatic islets, the
      generation of D-glucose 1-phosphate from UDP-glucose and PPI being eventually
      coupled to the generation of L-[U-14C]glutamate from 14C-labelled alpha
      ketoglutarate. The activity of the enzyme was about one order of magnitude lower
      in islet than liver homogenates. The affinity of the enzyme for either UDP
      glucose or PPi was comparable, however, in liver and islets. The activity of UDP
      glucose pyrophosphorylase was somewhat lower in islets from animals with
      inherited or acquired diabetes mellitus than in those from control rats. These
      findings are considered in connection with the accumulation of glycogen in islets
      of hyperglycemic animals.

PMID- 7804139
TI  - Induction of hepatic microsomal cytochrome P450 by dexamethasone in rhesus monkey
      (Macaca mulatta).
AB  - Intraperitoneal administration of 150 mg dexamethasone (DEX) Kg-1 body wt for
      four days to rhesus monkeys resulted in statistically significant increases in
      the activities of hepatic tyrosine aminotransferase (3 fold), microsomal
      cytochrome P450 (2 fold) and erythromycin N-demethylase (4 fold), but no change
      in the activities of aminopyrine N-demethylase and NADPH cytochrome c reductase.
      Three peaks were obtained from control or DEX-treated monkey livers on
      fractionation of detergent solubilized microsomes by anion exchange
      chromatography on DE-52. Peak II obtained from DEX-treated monkey microsomes on
      DE-52 demonstrated the highest specific activity of cytochrome P450 (5.84 nmol mg
      1 protein) as compared to other peaks from the same microsomes or any of the
      peaks obtained from the control microsomes. Sodium dodecyl sulfate polyacrylamide
      gel electrophoresis of the microsomes from control and experimental animals and
      peak II obtained after anion exchange chromatography of DEX-treated microsomes
      demonstrated the intensification of two polypeptides of 52.5 and 50 kDa. The
      results indicate that DEX is an inducer of cytochrome P450 and dependent
      erythromycin N-demethylase in non-human primate, Macaca mulatta.

PMID- 7804140
TI  - Univalent-cation-elicited acidification by yeasts.
AB  - Addition of univalent cations to sugar-metabolizing Saccharomyces cerevisiae,
      Schizosaccharomyces pombe and Lodderomyces elongisporus brought about a powerful
      acidification of the external medium with rates up to nearly 20 nmol H+ per min
      per mg dry wt. in S. cerevisiae, over 15 nmol in S. pombe, and 4.7 nmol in L.
      elongisporus. These rates were as much as 20 times, 5.5 times and 10.3 times,
      respectively. higher than in the absence of K+. Use of galactose-induced cells,
      of H(+)-ATPase-deficient mutants and observations over the entire growth curve
      indicated that the K+ effect on H+ extrusion is not connected with the H(+)
      ATPase function as such but rather depends on metabolic reactions producing ATP.
      The effect has apparently nothing to do with the electrical potential across the
      plasma membrane.

PMID- 7804141
TI  - Isolation and characterization of oryzatensin: a novel bioactive peptide with
      ileum-contracting and immunomodulating activities derived from rice albumin.
AB  - A novel bioactive peptide was isolated from the tryptic digest of rice soluble
      protein based on ileum-contracting and anti-opioid activities in the isolated
      guinea pig ileum. The structure of the peptide was Gly-Tyr-Pro-Met-Tyr-Pro-Leu
      Pro-Arg, and it was named oryzatensin. Oryzatensin showed a biphasic ileum
      contraction, which was characterized by a rapid contraction followed by a slower
      one. The latter was mediated by the cholinergic nervous system because it was
      inhibited by tetrodotoxin and atropine. Although oryzatensin showed weak affinity
      for mu-opioid receptors, the apparent anti-opioid activity seemed to be
      associated with the slower contraction. On the other hand, oryzatensin showed
      phagocytosis-promoting activity for human polymorphonuclear leukocytes and
      augmented the production of superoxide anion by human peripheral leukocytes.

PMID- 7804142
TI  - Oxidation of human red blood cells by a free radical initiator and effects of
      radical scavengers.
AB  - Haemolysis induced by a free radical initiator (4,4'azobis-(4-cyanovaleric acid)
      has been studied with transfusion blood. Azobis cyanovaleric acid caused an
      increase in haemolysis. The effect of alpha- and gamma-tocopherol, 2,2,5,7,8
      pentamethyl-6-chromanol and 2,2,7,8 tetramethyl-6-chromanol on the red blood cell
      haemolysis was studied. There was little difference in the antioxidant action of
      four chromanols studied. Compounds without the side chain appeared to suppress
      haemolysis as well as alpha- and gamma-tocopherol. These results suggest that the
      long side chain of vitamin E has little or no effect on its antioxidant activity
      in red blood cells. However "protection against haemolysis" was related to total
      chromanol content of red blood cells. Therefore by dividing "protection" by
      "total chromanol content" it can be seen that alpha-tocopherol has the highest
      antioxidant potency.

PMID- 7804143
TI  - Molecular cloning and characterization of the ovine CYP11B1 promoter.
AB  - The promoter region of the ovine P45011 beta gene has been cloned and sequenced.
      This clone contained 2068 bp of the regulatory region and 232 bp of the exon 1.
      Comparison of this sequence to other P45011 beta promoter sequences revealed six
      elements that may confer cAMP responsiveness and cell-specific expression to the
      ovine P45011 beta gene. We obtained consensus sequences for a number of cis
      acting elements needed to mediate cAMP responsiveness to the gene. We also report
      the presence of two new elements, CRE2 and a TRE, located far upstream from the
      translational site that may participate in the regulation of the ovine P45011
      beta gene.

PMID- 7804144
TI  - A new technique for enhancing luminol luminescent detection of free radicals and
      reactive oxygen species.
AB  - A novel technique is reported which makes use of (1) an improved method for
      solubilizing luminol at neutral pH along with (2) the addition of dimethyl
      sulfoxide to stabilize superoxide anion in the solutions in which luminescence is
      detected. These improvements resulted in (1) very low blank values of
      luminescence and (2) an approximately 6-fold increase in sensitivity of detection
      of peroxide and superoxide, as well as stabilizing the superoxide radical anion.
      The technique can also be used to evaluate the availability of antioxidants in
      biological homogenates and fluids.

PMID- 7804145
TI  - Regulation of phosphofructokinase from muscle and liver of rainbow trout by
      protein phosphorylation.
AB  - Phosphofructokinase (PFK) from both white skeletal muscle and liver of trout is
      controlled by reversible phosphorylation. In vitro phosphorylation of purified
      muscle PFK with the catalytic subunit of cAMP-dependent protein kinase led to a
      25% decrease in the S0.5 F6P and reduced inhibition by Mg.ATP and citrate.
      Phosphorylation of trout liver PFK lowered the I50 Mg.ATP (by 27%) but in vitro
      treatment with acid phosphatase reduced S0.5 F6P by 40% and increased I50 Mg.ATP
      by 50%. Thus, dephosphorylated trout liver PFK appears to be the more active
      enzyme form. Compared with mammalian PFK, the less rigorous effects of
      phosphorylation on trout liver PFK and relatively stronger phosphorylation
      control of skeletal muscle PFK may serve different patterns of carbohydrate
      metabolism in lower vertebrates, in particular the in situ processing of lactate
      in post-exercise muscle.

PMID- 7804146
TI  - Endocytosis of lysosomal acid phosphatase; involvement of mannose receptor and
      effect of lectins.
AB  - Acid phosphatase and beta-glucosidase are unique among lysosomal enzymes in that
      they have both high mannose and complex type sugasr chains, whereas
      oligosaccharide chains of lysosomal enzymes in matrix are of high mannose type.
      We have previously shown that beta-glucosidase was endocytosed into macrophages
      via an unidentified receptor different from a mannose/fucose receptor (K. Imai,
      Cell Struct. Funct. 13, 325-332, 1988). Here, we show that uptake of acid
      phosphatase purified from rat liver lysosomes into rat macrophages was inhibited
      by ligands for a mannose/fucose receptor and was mediated via an apparently
      single binding site with Kuptake of 24.7 nM. These results indicate that acid
      phosphatase and beta-glucosidase recognize different types of receptors even if
      they have similar sugar chains. Polyvalent concanavalin A which binds both to the
      enzyme and to macrophages specifically stimulated the uptake in a dose dependent
      manner, whereas wheat germ agglutinin and phytohaemagglutinin did not.

PMID- 7804147
TI  - Chemical modification of Lys-6 in Taiwan cobra phospholipase A2 with 4-chloro-3,5
      dinitrobenzoate.
AB  - Phospholipase A2 (PLA2) from Naja naja atra snake venom was modified with 4
      chloro-3,5-dinitrobenzoate, and one major carboxydinitrophenylated (CDNP) PLA2
      was separated by high performance liquid chromato-graphy. CDNP-PLA2 contained
      only one CDNP group on Lys-6 and showed a 93% drop in enzymatic activity.
      However, carboxydinitrophenylation did not significantly affect the secondary
      structure of the enzyme molecule as revealed by the CD spectra, and Ca2+ binding
      and antigenicity of CDNP-PLA2 were unaffected. Conversion of nitro groups to
      amino groups resulted in a partial restoration of enzymatic activity of CDNP-PLA2
      to 35% of that of native enzyme. These results suggested that the positively
      charged side chain of Lys-6 played a role in the enzymatic mechanism of PLA2.
      However, the partial restoration in PLA2 activity reflects that a distortion of
      the active conformation arising from incorporation of a bulky CDNP group should
      occur.

PMID- 7804148
TI  - Expression of a fibrinolytically active human pro-urokinase fusion protein in
      Escherichia coli.
AB  - The gene encoding human pro-urokinase(pro-UK) was cloned into plasmid pEZZ318 and
      fused to the gene coding for the signal peptide of staphylococcal protein A and
      IgG bindinging domain. The fusion protein which was synthesized under the control
      of T7 promoter in Escherichia coli and secreted into the growth medium, was found
      to be fibrinolytically active. Approximately 60% of the total activity was
      secreted into the culture medium, where levels of activity approached 150,000
      I.U./liter and about 40% of the total activity remained in the cell lysate with
      levels of activity around 100,000 I.U./liter. The fusion protein was purified in
      a single step by IgG affinity chromatography. These results demonstrate that
      human pro-UK can be synthesized and secreted by E. coli as a fibrinolytically
      active fusion protein.

PMID- 7804149
TI  - Expression of protein tyrosine phosphatase genes in the developing brain of mouse
      and rat.
AB  - We have examined the expression of protein tyrosine phosphatase genes in the
      embryonic brain of mouse and rat with reverse transcription-polymerase chain
      reaction. Several receptor and cytoplasmic types of tyrosine phosphatase genes
      were detected. Among them a novel gene was identified from mouse and rat brain,
      respectively. The partial amino acid sequences reveal that the new genes found in
      the developing brain of mouse and rat are homologous each other. Since they
      retain conserved phosphatase sequences, they may represent a family of protein
      tyrosine phosphatase gene that is commonly expressed in rodent brain.

PMID- 7804150
TI  - Kinetic studies of the Serratia marcescens extracellular nuclease isoforms.
AB  - Kinetic studies on the two major isoforms of Serratia marcescens nuclease, Sm2
      and Sm1, have revealed them to be functionally equivalent. Both isoforms display
      marked substrate inhibition by DNA and RNA. They both require magnesium for
      optimal activity, but retain low catalytic activity in its absence. Both are
      moderately inhibited by mononucleotides including 5'-ATP, 5'-AMP, 5'-TTP and 3'5'
      pTp. The two strongest mononucleotide inhibitors studied, 5'-ATP and 5'-AMP,
      display inhibition constants, KI, on the order of 10(-5) M. In assessing the
      strength of mononucleotide inhibition the type of nucleotide base appears to be
      more important than the number of phosphate moieties.

PMID- 7804151
TI  - Identification and characterization of thionucleosides in the total tRNA of
      cucumber cotyledons.
AB  - Total tRNA isolated from cucumber cotyledons grown in the presence of radioactive
      sulfur was analyzed for the occurrence of thionucleosides. The analysis revealed
      the presence of at least five thionucleosides which were identified as 5
      methylaminomethyl-2-thiouridine (mnm5s2U), 2-methylthio-N6-isopentenyladenosine
      (ms2i6A), 2-methylthio-N6-hydroxyisopentenyladenosine (ms2io6A), 5-methyl-2
      thiouridine (m5s2U) and N-[(9-beta-ribofuranosyl-2- methylthiopurine-2-yl)
      carbamoyl]-threonine (ms2t6A). A comparison of relative amounts of these
      thionucleosides in the total tRNAs of dark-, and light-grown cotyledons shows
      that the relative amounts of ms2i6A, ms2io6A and ms2t6A remain unchanged whereas
      mnm5s2U increases with a concomitant decrease in the relative amounts of m5s2U
      after light treatment of dark-grown cotyledons.

PMID- 7804152
TI  - Mumps and rubella consensus conference.

PMID- 7804153
TI  - IL-1 alpha antiproliferative and differentiative effects on Daudi lymphoma cells:
      multiparametric analysis.
AB  - Interleukin I alpha (IL-1) is a potent agent that induces a wide range of
      biological effects. In this study we analysed its effects on cell cycle
      progression and differentiation of Daudi lymphoma cells. The parallel analysis in
      light microscopy and cytofluorimetry by means of anti-BrdU monoclonal antibodies
      showed a reduced rate of proliferation (S phase) with a G1 arrest. These features
      were confirmed by the lower incorporation of [3H]-thymidine supporting the
      decrease in the rate of DNA synthesis. In addition this cytokine was able to
      induce differentiation after 24 hrs of treatment as assessed by the increased
      expression of Fc receptors (FcR) and morphological criteria. This multiparametric
      analysis gives evidence to the sensitivity to this cytokine of this peculiar cell
      line.

PMID- 7804154
TI  - Nucleolar organization as revealed in cycloheximide treated cells.
AB  - The nucleolar organisation has been studied in cycloheximide treated rat kangaroo
      cells. Within 1 h of treatment most nucleoli become loose and reveal a
      nucleolonemal network. With longer treatment the granules are scarce and the
      nucleolonemal network becomes more prominent. The network reveals units
      comparable to the rDNA transcriptional units in length. The nucleolonemal units
      consists of tufts of fibrils. When cycloheximide is withdrawn, granules reappear
      and obliterate the nucleolonemal network.

PMID- 7804155
TI  - Benzamide-induced changes in the actin cytoskeleton in human skin fibroblasts.
AB  - The incubation of human skin fibroblasts in the presence of 10 mM benzamide in
      Joklik's modification of Eagle's Minimal Essential Medium caused an extensive
      reorganization of actin filaments. The disappearance of stress fibers and changes
      in cell morphology were observed, whereas no changes in the microtubule
      architecture were noticed. The observed effects appeared fully reversible within
      3 hours after the removal of benzamide. The results are discussed in relation to
      the two known activities of benzamide as an anaesthetic and an inhibitor of ADP
      ribosylation.

PMID- 7804156
TI  - Increase in cytoskeletal actin induced by inositol 1,4-bisphosphate in saponin
      permeated pig platelets.
AB  - Inositol 1,4-bisphosphate (IP2) which rapidly accumulates during cell activation,
      strongly stimulates an increase in cytoskeletal actin in saponin-permeated
      platelets, and the effect is insensitive to 5'-Chloro-5'-deoxyadenosine. Within
      10 s, the amount of cytoskeletal actin in platelets rapidly increases by 41%, and
      then slowly increases further. IP2 induces the increase in cytoskeletal actin in
      a dose-dependent manner. The half-maximal effect requires approximately 2 microM
      of IP2. Inositol 1,4,5- triphosphate, the messenger for Ca2+ release, causes the
      increase in cytoskeletal actin, but is less effective than IP2. Inositol 1
      monophosphate and inositol 2-monophosphate have no effect on cytoskeletal actin.
      Phorbol 12-myristate 13-acetate, which has been shown to activate IP3 5'
      phosphatase through protein kinase C, stimulates the increase in cytoskeletal
      actin. Spermine, an inhibitor of IP3 5'-phosphatase, inhibits the thrombin
      stimulated increase in cytoskeletal actin. These results suggest that IP2 may be
      a messenger that controls the organization of actin filaments during cell
      activation. This study presents the first evidence for IP2 as a messenger during
      cell activation.

PMID- 7804157
TI  - Reproduction of nuclei in Pelomyxa palustris.
AB  - Light and electron micrographs were made of nuclei in Pelomyxa palustris, a
      unicellular, multinucleated giant amoeboid organism. We analyzed 1019 pelomyxae
      and classified their nuclei according to their location in the nuclear cycle. The
      majority of organisms (56.3%) had interphase nuclei, some of which contained
      spores of mostly 1-3 microns in diameter. The nuclei had disintegrated in 1.3% of
      organisms that appeared to have no nuclei. The remainder (42.4%) had nuclei in
      the form of spores (1 to 10 microns spheroids) that were in various stages of
      development and growth. Mitotic figures were seen in some of them, with several
      chromosome pairs per nucleus. Interchromosomal fibers were seen at anaphase, and
      newly formed "young" interphase nuclei were observed.

PMID- 7804158
TI  - Both glucose-type monosaccharides and one of their metabolites are required for
      activation of yeast plasma membrane H(+)-ATPase.
AB  - Saccharomyces cerevisiae and Schizosaccharomyces pombe cells were grown on D
      glucose, D-galactose, D-fructose, D-mannose, maltose, trehalose and ethanol. All
      these substrates were separately added to cells thus grown and the onset and rate
      of acidification mediated by the plasma membrane H(+)-ATPase were determined.
      Irrespective of the growth substrate, the best triggers of acidification in both
      species were fructose, mannose and glucose (with average rates of 5.2, 5.0 and
      4.8 nmol H+ per min per mg dry weight, respectively, for S. cerevisiae, and 4.5,
      6.8 and 5.8 for S. pombe). These were followed in S. cerevisiae by galactose in
      Gal-, Man- and Tre-grown cells (about 0.40 nmol H+) and by maltose in Mal- and
      Tre-grown cells (about 0.15 nmol H+). Trehalose elicited some response in only
      ethanol-grown cells while ethanol itself was completely ineffective in activating
      the H(+)-ATPase. In S. pombe, however, maltose caused an acidification rate of
      3.6 nmol H+ per min per mg dry wt., followed by EtOH (().38), Gal (0.13) and Tre
      (0.05). 6-Deoxy-D-glucose and 2-deoxy-D-glucose, not metabolized or improperly
      metabolized analogues of glucose, had no effect whatsoever. It appears that the
      sensor triggering the ATPase-activating pathway is a complex responding both to a
      glucose-type sugar (Glc, Man, Fru) and possibly identical with one of the glucose
      carriers, and to one of its metabolites, most probably fructose-6-phosphate.

PMID- 7804159
TI  - Immunohistochemical characterization of a stage-specific antigen during oogenesis
      and spermatogenesis recognized with monoclonal antibody.
AB  - In order to detect and characterize novel molecules which function in oogenesis,
      immunohistochemical study using a monoclonal antibody (MAb) raised against
      oocytes of Xenopus laevis was carried out. The distribution of the detectable
      molecule with MAb X-80, which specifically reacts with Xenopus previtellogenic
      oocytes; stages I and II (Dumont, 1972), in particular was analyzed. The hamster,
      mouse, chick, quail, Caenorhabditis elegans and Lilium longiflorum were also
      examined. Interestingly MAb X-80 bound not only in Xenopus oocytes but in its
      secondary spermatocytes and spermatids. Furthermore, MAb X-80 gave a similar
      staining pattern in the Lilium and other, although the stage when the positive
      reaction is detectable is different in the male and female germ cells.

PMID- 7804160
TI  - Purification and partial immunochemical characterization of a low molecular mass,
      diagnostic Echinococcus granulosus immunogen for sheep hydatidosis.
AB  - A hydatid specific antigen of 8 kDa molecular mass was affinity-purified from
      crude hydatid cyst fluid. Some of the epitopes recognised by antibodies in the
      sera from sheep with hydatidosis were periodate-sensitive. The purified 8 kDa
      antigen was observed to be a thermo-stable glycoprotein in its immunochemical
      characteristics. By immunofluorescence on acetone-fixed protoscolices anti-8 kDa
      monospecific IgG antibodies indicated the existence of the 8 kDa molecule on the
      hooklets of protoscolices. The purified antigen was used in an enzyme-linked
      immunosorbent assay for the detection of specific antibodies in sera from sheep
      hydatiodosis. Eighteen (90%) of 20 sera from sheep hydatidosis had antibodies to
      purified 8 kDa antigen while none of the sera from other parasitic infections or
      uninfected animals had any detectable levels of antibodies to 8 kDa antigen.
      Thus, the data on localization and recognition of hydatid specific 8 kDa molecule
      suggested that this may be one of the major molecules for specific
      immunodiagnosis and for modulating the hydatid disease process in infected hosts.

PMID- 7804161
TI  - The effects of extracellular slime from Staphylococcus epidermidis on phagocytic
      ingestion and killing.
AB  - Extracellular slime (Ecs) from three strains of Staphylococcus epidermidis was
      prepared and added to fresh suspensions of polymorphonuclear neutrophils.
      Phagocytic ingestion and killing of opsonised and unopsonised S. epidermidis
      strains was assessed over time using slide preparations stained by the Gram's
      method and microbiological culture. Both phagocytic ingestion and killing were
      inhibited. Investigation as to one possible mechanism of action of Ecs on
      phagocytes was performed using 1 mu polystyrene spheres which were incubated
      overnight with Ecs. It was found that the surface tension was altered with Ecs
      making the beads more hydrophilic, a factor which may interfere with the
      phagocytic response to infection.

PMID- 7804162
TI  - Use of cyclodextrin as an agent to induce excretion of Bordetella pertussis
      antigens.
AB  - This paper attempts to provide an explanation for the effect of cyclodextrin on
      the yield of Bordetella pertussis soluble antigens. It was demonstrated that the
      addition of cyclodextrin to the synthetic Stainer-Scholte liquid medium enhances
      the level of the intracellular form of adenylate cyclase (200 kDa) in the
      supernate. In addition to this effect, it has been reported that cyclodextrin
      also enhances the levels of two other extracellular proteins, pertussis toxin and
      filamentous hemagglutinin. As these antigens are structurally different, it seems
      that the effect of cyclodextrin is not specific. With the use of different buffer
      systems of well-known action on outer membrane stability it was possible to
      determine a relationship between the presence of cyclodextrin, destabilisation of
      the outer membrane and the release of proteins. It was determined that the
      cyclodextrin did not modify the fluidity of B. pertussis cells but produced a
      change of outer membrane permeability.

PMID- 7804163
TI  - A cell-free Salmonella typhimurium extract modulates interleukin-2 (IL-2)
      receptor expression but not IL-2-stimulated responses of murine splenic
      lymphocytes.
AB  - In a previous study, we observed that a cell-free Salmonella typhimurium extract
      induced suppression of mitogen-induced T-cell proliferation and this suppression
      involved non-responsiveness of T-cells to interleukin-2 (IL-2). In this study, we
      found that a cell-free S. typhimurium extract modulated IL-2 receptor (IL-2R)
      expression on phytohemagglutinin (PHA)-stimulated murine spleen cells and this
      was a mechanism of T-cell non-responsiveness to IL-2, but did not affect IL-2
      binding to IL-2R and the consequent responses. Western blotting using anti
      phosphotyrosine antibodies showed that IL-2R-mediated tyrosine phosphorylation of
      protein substrates in PHA-activated murine splenic T-cells, which express a high
      affinity IL-2R (alpha- and beta-chains), was not affected by treatment with the
      S. typhimurium cell-free extract. Furthermore, PHA-activated spleen T-cells
      responded to recombinant IL-2 and this was not inhibited by the extract.
      Surprisingly, IL-2R expression was augmented by treatment with the extract,
      although this was independent of IL-2 production. These results suggest that the
      suppression of T-cell proliferation induced by the Salmonella cell-free extract
      was associated with augmentation of IL-2R expression, rather than down-regulation
      of the IL-2 response. This may be a mechanism responsible for the Salmonella
      extract-evoked suppression of mitogen-induced T-cell proliferation.

PMID- 7804164
TI  - Inhibitory effect of saliva from secretors and non-secretors on binding of
      meningococci to epithelial cells.
AB  - Carriage of Neisseria meningitidis B:4:P1.15 was higher among non-secretors
      during a school outbreak of meningitis; non-secretors had lower levels of anti
      meningococcal salivary IgM. Flow cytometry was used to assess effects of secretor
      and non-secretor saliva on binding of B:4:P1.15 to buccal epithelial cells: (1)
      to assess inhibition by IgA and IgM; and (2) to assess contributions of salivary
      antibodies to inhibitory activities. Greater inhibition was obtained with
      secretor saliva: pooled (P = 0.049); fresh (P = 0.0001). Purified IgA (P = 0.02)
      and IgM (P = 0.03) were equally inhibitory. After absorption of anti
      meningococcal antibodies, there was still significant inhibitory activity in the
      pools: secretors (P = 0.018); non-secretors (P = 0.005). These results indicate
      that both secretory immunoglobulins and other factors contribute to protection
      against colonisation by meningococci and might explain the increased carriage of
      B:4:1.15 in this population.

PMID- 7804165
TI  - Expression of antigenically distinct fimbriae with hemagglutination and HeLa cell
      adherence properties by an enteroaggregative Escherichia coli strain belonging to
      the enteropathogenic serogroup.
AB  - An enteroaggregative Escherichia coli (EAggEC) strain (DS92), isolated from a
      case of infantile diarrhea, was shown to express mannose-resistant
      hemagglutination and HeLa cell adhering properties when grown at 37 degrees C but
      not at 28 degrees C. Cellular adherence properties of DS92, which belonged to
      enteropathogenic serogroup 0125, were shown to correlate well with the expression
      of fimbriae that were encoded by a 112 kb plasmid. The fimbriae of the EAggEC
      strain DS92 were composed of 20 kDa subunit proteins and were serologically
      distinct from fimbrial or non-fimbrial cell surface antigen(s) of other
      diarrheagenic E. coli strains including the reference EAggEC strain 17-2.
      Interestingly, the 20-kDa fimbrial protein was found to be antigenically related
      to 18- and 14.5-kDa cell surface proteins of two other locally isolated EAggEC
      strains belonging to the enteropathogenic serogroup 086.

PMID- 7804166
TI  - Antibody-independent protection in mice against type Ia group B streptococcus
      lethal infection.
AB  - There is ample evidence that protection against group B streptococcal (GBS)
      disease, both in experimental animals and in humans, is related to the presence
      of specific antibodies and complement. However, until now the possibility of
      increasing resistance to GBS infection by potentiating natural cell-mediated
      immunity in the host, has not been explored. In this study we examine the effect
      of administering in vivo MVE-2 (a polymer fraction of 1,2-co-polymer of divinyl
      ether and maleic anhydride) and inactivated Candida albicans (CA) cells on mouse
      resistance to the reference strain type Ia 090 GBS (GBS-090) lethal infection.
      MVE-2 and CA, respectively a synthetic and a microbial biological response
      modifier (BRM), are strong inducers and activators of natural resistance
      effectors, such as natural killer (NK) cells, macrophages and polymorphonuclear
      cells (PMN). The results showed that MVE-2 protected 100% CD-1 mice from a
      systemic lethal challenge with GBS-090 (5 x 10(3) microorganisms/mouse) when
      administered 3 days before infection at dose of 50 mg kg-1. CA treatment, in five
      doses (CA-5d) over 14 days protected 100% mice when administered at 2 x 10(7)
      cells/mouse and when the last CA injection was given 1 day before the GBS-090
      challenge. Instead, when the GBS-090 challenge was performed by intraperitoneal
      route, protection was obtained with CA-5d treatment but not with MVE-2. The
      possibility that MVE-2 or CA stimulated a rapid production of specific antibodies
      against GBS-090 infection was excluded by the ELISA assay. Evidence exists that
      NK cells do not play a primary role as effectors in the MVE-2 and CA conferred
      protection since the strong reduction in NK activity, due to in vivo
      administration of anti-asialo GM1 antibodies before GBS-090 infection, did not
      influence the BRM-induced protection. Besides, high NK activity levels, induced
      by in vivo rhIL-2 administration, did not protect the mice against GBS-090
      infection. Both studies on in vivo clearance and in vitro microbicidal activity,
      showed that, after 1 h, immunopotentiated effectors were unable to kill GBS-090,
      but were highly effective against GBS type VI. These results seem to indicate
      that intracellular GBS-090 killing is a slow process requiring more than 1 h.
      This study demonstrates that it is possible to increase resistance to GBS-090
      lethal infection by BRMs, by potentiating the antibody-independent microbicidal
      activity of the phagocytes.

PMID- 7804167
TI  - Protection by dexamethasone from a lethal infection with Listeria monocytogenes
      in mice.
AB  - The effects of dexamethasone (DEX) on a lethal infection with Listeria
      monocytogenes were studied in mice. Mice were completely protected against the
      lethal infection when treated with 3.3 mg per kg of DEX. The effect was observed
      only when DEX was injected before infection. The control mice died from day 3 to
      day 5 of infection, whereas DEX-treated mice could eliminate L. monocytogenes
      cells from the organs by day 11 of infection. High titres of endogenous tumour
      necrosis factor (TNF), interleukin-6 (IL-6) and gamma interferon (IFN-gamma) were
      induced in the bloodstreams and organs of the drug-free mice. DEX suppressed IL-6
      production, but augmented TNF and IFN-gamma production within 24 h of infection,
      whereas production of all three endogenous cytokines was suppressed in the DEX
      treated mice on day 3 of infection when the control mice began to die. These
      results suggest that DEX shows a protective effect on a lethal infection with L.
      monocytogenes in mice and that regulation of production of endogenous cytokines
      might be involved in the effect of DEX.

PMID- 7804168
TI  - Binding of tissue-type plasminogen activator (t-PA) to Neisseria meningitidis and
      Haemophilus influenzae.
AB  - Forty-nine bacterial strains representing five species known to interact with
      human plasminogen were tested for the ability to bind the two major human
      plasminogen activators, t-PA and urokinase. The bacterial species tested included
      Haemophilus influenzae, Neisseria meningitidis, Streptococcus pyogenes,
      Streptococcus equisimilis and human group G streptococci. All N. meningitidis and
      11 of 14 H. influenzae strains displayed substantial binding of t-PA with values
      in the range of 20-46%. On the contrary, none of the streptococcal strains bound
      significant amounts of tPA. With urokinase no binding could be found for any of
      the bacterial species tested. Scatchard analysis with a selected H. influenzae
      strain (HI23354) demonstrated 10,000 receptors per bacterium for t-PA with a Kd
      value of about 20 nmol l-1. The corresponding values with a selected N.
      meningitidis strain (Mo 52) was 8500 receptors per bacterium and 70 nmol l-1. t
      PA binding could be reduced about 40% by the addition of 10 mmol l-1 of the
      lysine analogue epsilon-aminocaproic acd (EACA) whereas no inhibitory effect
      could be demonstrated with arginine. Addition of 2 mumol l-1 of plasminogen which
      is enough to occupy all bacterial sites for plasminogen did not interfere with
      the t-PA binding, suggesting that the receptors for t-PA and plasminogen are
      distinct. Using very high plasminogen concentrations however, t-PA binding could
      be reduced by about 50% possibly due to an interaction between t-PA and
      plasminogen in the fluid phase. Our results demonstrate the occurrence of a
      previously unknown type of bacterial receptor that is capable of specifically
      binding t-PA.

PMID- 7804169
TI  - The role of infectious agents in sudden infant death syndrome.
AB  - Epidemiological factors associated with susceptibility to respiratory infections
      are similar to those associated with Sudden Infant Death Syndrome. Here we review
      the evidence that respiratory pathogens might be involved in some cases of Sudden
      Infant Death Syndrome in the context of factors identified in epidemiological
      studies of cot deaths: the age range affected; mother' smoking; respiratory viral
      infections; immunisation status. Both laboratory and epidemiological evidence
      suggests that vulnerability of infants to infectious agents depends on
      interactions between genetic, developmental and environmental factors that
      contribute to colonisation by microorganisms, the inflammatory and specific
      immune responses and the infants' physiological responses to inflammatory
      mediators. A model is proposed to explain how microorganisms might trigger a
      series of events resulting in some of these unexpected deaths and discusses how
      the the present recommendations regarding child care practices might help reduce
      the numbers of Sudden Infant Death Syndrome cases associated with infectious
      agents.

PMID- 7804170
TI  - Raising a din.

PMID- 7804171
TI  - An historical approach to care.

PMID- 7804172
TI  - Osteoporosis: condition of our time.

PMID- 7804173
TI  - Therapeutic mealtimes.

PMID- 7804175
TI  - Glycaemic control reduces incidence of morbidity.

PMID- 7804174
TI  - Continence management.

PMID- 7804176
TI  - Whose choice is it anyway?

PMID- 7804177
TI  - Myths in FOCUS.

PMID- 7804178
TI  - Maximum safety.

PMID- 7804179
TI  - As I was saying....

PMID- 7804180
TI  - Solidarity in the ranks.

PMID- 7804181
TI  - Economies of scale.

PMID- 7804182
TI  - How did they all survive? An analysis of American nurses' experiences in Japanese
      Prisoner-of-War Camps.

PMID- 7804183
TI  - "Little sufferers." Sick children in late-nineteenth-century Toronto.

PMID- 7804184
TI  - Lavinia Lloyd Dock. The Henry Street years.

PMID- 7804185
TI  - The Navajo experience of Elizabeth Forster, public health nurse.

PMID- 7804186
TI  - Nursing in Germany. A historical study of the Jewish presence.

PMID- 7804187
TI  - "Crowning the edifice." Ethel Fenwick and state registration.

PMID- 7804188
TI  - The historical relationship of the Canadian Association of University Schools of
      Nursing and the Canadian Nurses Association.

PMID- 7804189
TI  - "A good nurse cannot be bought with money". The development of the professional
      and industrial roles of the Nursing Organization in Queensland, Australia, 1904
      1950.

PMID- 7804190
TI  - Sister Mary Joseph Croke. Another voice from the Crimean War, 1854-1856.

PMID- 7804191
TI  - In service to the fifth wheel. Katharine Prescott Wormeley and her experiences in
      the United States Sanitary Commission.

PMID- 7804192
TI  - Courage to care. The Sisters of the Holy Cross in the Spanish-American War.

PMID- 7804193
TI  - Heroines of the good fight. Testimonies of U.S. volunteer nurses in the Spanish
      Civil War, 1936-1939.

PMID- 7804194
TI  - Toxoplasma gondii: strain- and host cell-dependent induction of stage
      differentiation.

PMID- 7804195
TI  - Bidirectional effectors of a group I intron ribozyme from Pneumocystis carinii.
AB  - The L-arginine acts stereoselectively on the Pc1.LSU nuclear group I intron of
      Pneumocystis carinii, competitively inhibiting the first step of the splicing
      reaction and stimulating the second step. A number of arginine-related compounds
      are more potent than L-arginine as stimulators and inhibitors. The most potent
      peptides tested are 10,000 times as effective as L-arginine in inhibiting
      ribozyme activity, and nearly 400 times as effective as stimulators. This
      phenomenon indicates that ribozymes, like protein enzymes, can interact with non
      substrate low molecular weight compounds, and that non-nucleic acid agents might
      be developed as drugs acting on RNA targets.

PMID- 7804196
TI  - Typing of Pneumocystis carinii strains that infect humans based on nucleotide
      sequence variations of internal transcribed spacers of rRNA genes.

PMID- 7804197
TI  - Sensitivity of taxonomically diverse fungi to pentamidine isethionate.

PMID- 7804198
TI  - Genomic and isoenzymatic markers of Pneumocystis from different host species.

PMID- 7804199
TI  - Evaluation of anti-Pneumocystis agents using flow cytometry.

PMID- 7804200
TI  - Sequence differences in the rRNA ITS regions identify specific isolates of P.
      carinii.

PMID- 7804202
TI  - Susceptibility of Pneumocystis carinii to a Pichia anomala killer toxin.

PMID- 7804201
TI  - DNA analysis of Pneumocystis carinii infecting Finnish and English shrews.

PMID- 7804203
TI  - Sodium transport inhibitors decrease proliferation of Pneumocystis carinii in
      short-term culture.

PMID- 7804204
TI  - Uptake and metabolism of fluorescent lipid analogs by Pneumocystis carinii.

PMID- 7804205
TI  - Detection of Pneumocystis DNA in serum and circulating cells is not a good
      diagnostic marker for Pneumocystosis in HIV patients.

PMID- 7804206
TI  - A technique for cloning the telomeres and subtelomeric regions from Pneumocystis
      carinii.

PMID- 7804207
TI  - Antigenic differences among genetically distinct types of rat-derived
      Pneumocystis carinii.

PMID- 7804208
TI  - Chromosomal organization of MSG antigen genes of rat Pneumocystis carinii: tandem
      repeat and unique 5' UTR sequence encoding intron.

PMID- 7804209
TI  - Detection of DNA sequences identical to Pneumocystis carinii in samples of
      ambient air.

PMID- 7804210
TI  - Chromosomal localization of 20 genes to five distinct pulsed field gel karyotypic
      forms of rat Pneumocystis carinii.

PMID- 7804211
TI  - Genetic diversity of Pneumocystis carinii from different host species at the beta
      tubulin gene locus and at the internal transcribed spacer regions of the rRNA
      gene cluster.

PMID- 7804212
TI  - Coinfection of rats with genetically diverse forms of Pneumocystis carinii
      demonstrated by P. carinii inosine monophosphate dehydrogenase gene polymorphism.

PMID- 7804213
TI  - Administration of intraliposomal CP20961 to mice activates peritoneal macrophages
      and augments serum antibody response to Toxoplasma gondii.

PMID- 7804214
TI  - Assessment of Pneumocystis carinii DNA content.

PMID- 7804215
TI  - Revised nomenclature for Pneumocystis carinii. The Pneumocystis Workshop.

PMID- 7804216
TI  - Pneumocystis carinii: what is it and from whence does it come?

PMID- 7804217
TI  - ATCC--an international repository for Pneumocystis strains.

PMID- 7804218
TI  - Characterization of ribonuclease P from Toxoplasma gondii.

PMID- 7804219
TI  - Alterations in cell surface glycosylation, heparin, and chondroitin sulfate do
      not modify invasion of CHO cells by the PTg B strain of Toxoplasma gondii.

PMID- 7804220
TI  - Evaluation of strategies to reduce the risk of congenital toxoplasmosis: a
      decision tree analysis approach.

PMID- 7804221
TI  - Experimental murine toxoplasmic retinochoroiditis.

PMID- 7804222
TI  - Tissue cyst formation of Toxoplasma gondii T-263 in cell culture.

PMID- 7804223
TI  - Development of bradyzoites of Toxoplasma gondii in vitro.

PMID- 7804224
TI  - Toxoplasma workshop overview.

PMID- 7804225
TI  - In vitro assays of maduramicin activity against Cryptosporidium parvum.

PMID- 7804226
TI  - Ultrastructural identification of AIDS associated microsporidiosis.

PMID- 7804227
TI  - Treatment of acute and chronic Cryptosporidium parvum infections in mice using
      clarithromycin and 14-OH clarithromycin.

PMID- 7804228
TI  - Genetic markers differentiate C. parvum isolates.

PMID- 7804229
TI  - Flow cytometry as a possible method of isolation of spores of the microsporidian
      Enterocytozoon bieneusi.

PMID- 7804230
TI  - Identification of a type II topoisomerase gene from Cryptosporidium parvum.

PMID- 7804231
TI  - In vitro detection of anti-Cryptosporidium parvum antibody secreting cells by
      polyclonal activation of human tonsil mononuclear cells.

PMID- 7804232
TI  - Immunofluorescence and western blot analysis of microsporidia using anti
      Encephalitozoon hellem immunoglobulin G monoclonal antibodies.

PMID- 7804233
TI  - Travellers diarrhea associated with Cyclospora sp.

PMID- 7804234
TI  - Intestinal microsporidiosis: about clinical characteristics and laboratory
      diagnosis.

PMID- 7804235
TI  - IFN-gamma and LPS induce murine macrophages to kill Encephalitozoon cuniculi in
      vitro.

PMID- 7804236
TI  - First case of Enterocytozoon bieneusi infection in the Czech Republic: comments
      on the ultrastructure and teratoid sporogenesis of the parasite.

PMID- 7804237
TI  - In vitro sensitivity of Encephalitozoon cuniculi and E. hellem to albendazole.

PMID- 7804238
TI  - Cryptosporidium and microsporidial beta-tubulin sequences: predictions of
      benzimidazole sensitivity and phylogeny.

PMID- 7804240
TI  - Development of a precocious strain of Cryptosporidium parvum in neonatal calves.

PMID- 7804239
TI  - Immunofluorescence detection of Cryptosporidium parvum in Caco-2 cells: a new
      screening method for anticryptosporidial agents.

PMID- 7804241
TI  - Qinghaosu (artemisinin) and derivatives fail to protect neonatal BALB/c mice
      against Cryptosporidium parvum (Cp) infection.

PMID- 7804242
TI  - Cloning of a partial length cDNA encoding the C-terminal portion of the 75-77-kDa
      antigen of Trypanosoma cruzi.
AB  - It has been suggested that several Trypanosoma cruzi antigens have possible
      protective epitopes which may be suitable vaccine candidates. We found previously
      that animals resistant to T. cruzi infection produced antibodies against the 75
      77-kDa parasite antigen. To test the ability of the recombinant form of this
      antigen to protect animals from T. cruzi infection, the cDNA which encodes a
      portion of the 75-77-kDa antigen was cloned using a cDNA library constructed in
      an orientation-specific bacteriophage expression vector (lambda gt 11) from poly
      (A)+ RNA of Brazil strain epimastigotes. One clone, named SFS-40, was selected by
      screening the library using affinity purified antibodies specific for the 75-77
      kDa parasite antigen as probe. The cDNA corresponding to the 1.7-kilobase insert
      of SFS-40 was subcloned into plasmid vectors and characterized. The cDNA sequence
      encodes a polypeptide of about 40 kDa. The putative product of the cDNA was
      homologous to members of the 70-kDa stress protein family. When epimastigotes
      were shifted from 29 degrees C to 37 degrees C, there was no change in the level
      of SFS-40 mRNA. In contrast, the 70-kDa heat shock protein mRNA of the parasite
      was increased about four fold by this treatment.

PMID- 7804243
TI  - Role of a Gal/GalNAc-specific sporozoite surface lectin in Cryptosporidium parvum
      host cell interaction.

PMID- 7804244
TI  - Detection of a prolonged C. parvum infection in immunocompetent adult C57BL/6
      mice.

PMID- 7804245
TI  - Evidence for the ancestral origin of group I introns in the SSUrDNA of Naegleria
      spp.
AB  - The sequence variation within the group I intron in five Naegleria spp. was
      studied and compared with the sequence variation within the flanking small
      subunit ribosomal DNA. Considerable sequence divergence was observed in the
      introns as well as in the rDNA. In the intron deletions and insertions are only
      detected in the sequence contributing to the secondary structure, not in the open
      reading frame. Most of the sequence variation is detected in the unpaired loops.
      In the case of nucleotide substitution in helices, compensating base pair changes
      were observed. The sequence variation does not induce variation in the secondary
      structure model. The phylogenetic tree based on the intron sequences is similar
      to the tree based on the flanking rDNA sequences. This observation indicates that
      the intron might have been acquired at an early stage in evolution, and lost in
      the majority of Naegleria spp.

PMID- 7804246
TI  - Isolation of Cryptosporidium and bovine cDNA clones from a Cryptosporidium
      infected MDBK cell line subtraction library.

PMID- 7804247
TI  - Tubulin genes in the algal protist Euglena gracilis.
AB  - Alpha- and beta-tubulin cDNA were selected from a Euglena lambda gt11 expression
      library, recloned and either sequenced (alpha-tubulin cDNA) or hybridized to
      Euglena RNA and DNA (alpha- and beta-tubulin cDNA). RNA for hybridization was
      extracted at 30 minute intervals after flagellar amputation and quantitated for
      cDNA binding. Unlike previous reports on most other flagellates, no net increase
      in either alpha- or beta-tubulin RNA could be detected during regeneration-
      suggesting steady state or constitutive tubulin RNA synthesis. Incubation of the
      cDNA with genomic DNA after restriction digestion produced patterns of
      hybridization consistent with the presence of one to two kinds each of the alpha-
      and beta-tubulin genes. The deduced amino acid sequence of the alpha-tubulin cDNA
      was more than 90% identical to the alpha-tubulins of Trypanosoma, Chlamydomonas,
      Naegleria, Tetrahymena and higher plants. The carboxy terminus of the alpha
      tubulin cDNA and the previously sequenced beta-tubulin of Euglena showed greatest
      identity to the carboxy terminus of the tubulins from Trypanosoma brucei. The
      sequence data for alpha- and beta-tubulins of Euglena provides direct evidence
      for the similarity of two gene products from euglenas and trypanosomes and adds
      support to earlier suggestions that these organisms are phylogenetically related.

PMID- 7804248
TI  - The micronuclear gene encoding beta-telomere binding protein in Oxytricha nova.
AB  - The micronuclear version of the gene encoding beta-telomere binding protein (beta
      TBP) in Oxytricha nova has been sequenced and compared to the macronuclear beta
      TBP gene, previously described. The micronuclear gene contains three AT-rich
      internal eliminated sequences (IES) of 37, 40, and 43 bp and four macronuclear
      destined sequences (MDS). The IES interrupt the gene once near the 5' end of the
      coding region and twice in the 3' trailer downstream from the TGA stop codon. The
      sequences of the micronuclear and macronuclear genes are colinear. Thus, the
      micronuclear beta-TBP gene is not scrambled, which contrasts with the highly
      scrambled state among the 14 MDS in the micronuclear alpha-TBP gene.

PMID- 7804249
TI  - The identification and characterization of a polar tube reactive monoclonal
      antibody.

PMID- 7804250
TI  - The sequence of the Hartmannella vermiformis small subunit rRNA coding region.
AB  - The Hartmannella vermiformis small-subunit rRNA coding region was amplified, and
      the amplified DNA was cloned and sequenced. The coding region is 1,840
      nucleotides long, and is typical of eukaryotic rRNA genes in both size and
      composition. Different clones contained different nucleotides at three positions.

PMID- 7804252
TI  - In vivo efficacy of albendazole against Encephalitozoon cuniculi in SCID mice.

PMID- 7804251
TI  - "Fenestrin" and conjugation in Tetrahymena thermophila.
AB  - Certain monoclonal antibodies interact with proteins of Tetrahymena thermophila
      found in the conjugation junction as well as around the gametic nuclei
      (pronuclei) of conjugating cells; they also react with the oral primordium and
      fission zone of vegetative cells and with the cytoproct and contractile vacuole
      pores of all cells. One of these (FXIX-3A7) was investigated in detail.
      Immunogold labelling suggests that the material labelled by the 3A7 monoclonal
      antibody, which we call "fenestrin," is located beneath the epiplasm (membrane
      skeleton). Immunoblots reveal that the major and perhaps sole antigen is a 64 kDa
      polypeptide, found in two isoelectric variants. Developmental studies implicate
      fenestrin in two processes involved in conjugation. The first is "tip
      transformation." During preliminary starvation ("initiation"), labelling of
      fenestrin first appeared as a spot at the anterior end of starved mature cells,
      then after mixing of different mating types ("costimulation") it extended
      posteriorly along the anterior suture. After pairing, this region spread to form
      a widened plate. The second process is pronuclear transfer. Fenestrations
      representing channels between the conjugating cells began to appear 0.5 to 1 h
      after the conjugants united, and eventually merged to form a small number of
      temporary large holes during exchange of the transfer pronuclei. A fenestrin
      envelope also enclosed both the transfer and resident pronuclei; a strand of
      fenestrin connected the two. Shortly after pronuclear transfer, both transfer and
      resident pronuclei were released from fenestrin caps and fused to produce a
      zygotic nucleus (synkaryon) not associated with fenestrin Fenestrin thus appears
      to be intimately involved in the process of pronuclear exchange.

PMID- 7804253
TI  - kDNA and rDNA sequences reveal a phylogenetic cluster of species originally
      placed in different genera of trypanosomatids.
AB  - Hybridization using kDNA and rDNA sequences as probes was performed to study
      phylogenetic relatedness of different species of trypanosomatids. Using this
      approach, we identified five organisms which had been classified as Phytomonas
      and Herpetomonas that were more closely correlated to each other phylogenetically
      than to any other species or isolates from either genera. These findings raise
      doubts about the validity of the current classification of Trypanosomatidae.
      Finally, we demonstrated the usefulness of kDNA sequences as an alternative to
      genomic sequences in obtaining phylogenetic information on trypanosomatids.

PMID- 7804254
TI  - Monoclonal antibody to a bacterial endonuclear symbiont Holospora cross reacts
      with proteins of contractile vacuole radial canals of Paramecium species.
AB  - A monoclonal antibody (mAb) IR-2-1 was raised against a 67-kDa protein purified
      from the macronucleus-specific bacterial symbiont Holospora obtusa of Paramecium
      caudatum. The mAb was found to react with two bands (31 and 67-kDa) on gels of H.
      obtusa. Indirect immunofluorescence microscopy showed that these antigens were
      distributed inside the cells. However, unexpectedly, this mAb also cross reacted
      with the radial arms of the contractile vacuole in P. caudatum, P. tetraurelia,
      P. multimicronucleatum, P. jenningsi and P. bursaria as well as with their
      cytoplasm. Immunoelectron microscopy showed that the antigens were located on the
      decorated spongiome of the radial arms. In immunoblots, mAb IR-2-1 reacted with a
      band of 67 kDa in all Paramecium species examined. However, no band appeared in
      the immunoblot of isolated macronuclei of H. obtusa-free P. caudatum and no label
      was seen in the nuclear matrix of the macronucleus of air-dried P. caudatum.
      These results suggest that the 67-kDa antigen found in H. obtusa was not imported
      from the host macronucleus and the same antigen in the host contractile vacuoles
      and cytoplasm were not derived from the symbiont. These results also showed that
      an epitope on the decorated spongiome of the Paramecium species is shared by its
      bacterial symbiont. In contrast to the decorated tubule-specific mAb, DS-1, the
      antigens for IR-2-1 appeared to be loosely membrane bound as they were lost in
      paraformaldehyde fixed and acetone permeabilized Paramecium.

PMID- 7804255
TI  - Isolation and partial characterization of Cryptosporidium sporozoite and oocyst
      wall recombinant proteins.

PMID- 7804256
TI  - Kinetic and isotypic analysis of specific immunoglobulins from crew members with
      cryptosporidiosis on a U.S. Coast Guard cutter.

PMID- 7804257
TI  - Pilot-scale ozone inactivation of Cryptosporidium.

PMID- 7804258
TI  - Search for cyanobacterium-like bodies in the stools of travellers with diarrhoeal
      illness.

PMID- 7804259
TI  - Diagnostic approaches for Encephalitozoon infections in patients with AIDS.
AB  - In conclusion, at the current time the most important task of the laboratory for
      proper clinical management of the patient with microsporidiosis is to perform
      genus-level diagnosis of the agent, i.e. distinguishing Encephalitozoon sp.
      infection from other microsporidial agents including Septata, Enterocytozoon,
      Nosema, and Pleistophora. This can be performed in any well-equipped pathology
      department with access to electron microscopy. If species identification is
      desired, we currently recommend consultation with one of several laboratories
      specializing in this area until diagnostic reagents become more widely available.

PMID- 7804260
TI  - Male genital tract microsporidiosis and AIDS: prostatic abscess due to
      Encephalitozoon hellem.

PMID- 7804261
TI  - Electronmicroscopic and electrophoretic studies of microsporidian prespore stages
      isolated from infected host cells by gradient centrifugation on Percoll.

PMID- 7804262
TI  - Enzyme histochemical identification of the Golgi apparatus in the microsporidian,
      Glugea stephani.

PMID- 7804263
TI  - The in vitro activity of albendazole against Encephalitozoon cuniculi.

PMID- 7804264
TI  - Effect of colchicine on microtubules in Cryptosporidium parvum.

PMID- 7804265
TI  - Development of patent gut infections in immunosuppressed adult C57BL/6N mice
      following intravenous inoculations of Cryptosporidium parvum oocysts.

PMID- 7804266
TI  - Cryptosporidium parvum: a decade of effort. An overview of the Cleveland
      workshop.

PMID- 7804267
TI  - Human microsporidiosis: past and present, an overview of the Cleveland workshop.

PMID- 7804268
TI  - Toxoplasma gondii soluble products induce cytokine secretion by macrophages and
      potentiate in vitro replication of a monotropic strain of HIV.

PMID- 7804269
TI  - Pneumocystis cross infection experiments using SCID mice and nude rats as
      recipient host, showed strong host-species specificity.

PMID- 7804270
TI  - Comparison of the antigenic recognition of the major surface glycoprotein of
      Pneumocystis carinii isolated from different rat strains.

PMID- 7804272
TI  - Purine metabolism in Pneumocystis carinii.

PMID- 7804271
TI  - Identification of two genetically distinct strains of Pneumocystis carinii in
      infected ferret lungs.

PMID- 7804273
TI  - Pneumocystis carinii detected in air.

PMID- 7804274
TI  - Measurement of protein biosynthesis in Pneumocystis carinii to investigate the
      effects of translation-specific inhibitors.

PMID- 7804275
TI  - Use of fluorescent probes to investigate the metabolic state of Pneumocystis
      carinii mitochondria.

PMID- 7804276
TI  - Safety aspects of a vaccine for cats containing a Toxoplasma gondii mutant
      strain.

PMID- 7804277
TI  - Extent of fungal contamination in rat-derived Pneumocystis carinii extracts and
      the effect on uptake of para-aminobenzoic acid.

PMID- 7804278
TI  - DNA amplification of a portion of the phosphomannose isomerase (PMI) gene in
      Pneumocystis carinii-enriched extracts.

PMID- 7804279
TI  - Ultrastructural, genomic, isoenzymatic and biological features make it possible
      to distinguish rabbit Pneumocystis from other mammal Pneumocystis strains.

PMID- 7804280
TI  - Different amplification efficiency and nucleotide sequence variation in various
      Pneumocystis isolates from humans and rats.

PMID- 7804281
TI  - Does Pneumocystis carinii remain infectious in the bloodstream?

PMID- 7804282
TI  - Identification of an epoxy fatty acid in Pneumocystis carinii lipids.

PMID- 7804283
TI  - Extraordinarily low number of ribosomal RNA genes in P. carinii.

PMID- 7804284
TI  - Immuno electron microscopy of Pneumocystis carinii exposed to a beta-1-3 glucan
      synthase inhibitor LY 302146.

PMID- 7804285
TI  - Role of IL-12 in the initiation of cell mediated immunity by Toxoplasma gondii
      and its regulation by IL-10 and nitric oxide.

PMID- 7804286
TI  - The composition of Pneumocystis carinii phospholipids.

PMID- 7804287
TI  - Effects of environmental factors and disinfectants on the survival of
      Pneumocystis carinii outside the host.

PMID- 7804288
TI  - A preliminary characterization of the Pneumocystis carinii dihydroorotate
      dehydrogenase.

PMID- 7804289
TI  - Isoprenoid metabolism in Pneumocystis carinii.

PMID- 7804290
TI  - Evaluation of procedures used to isolate Pneumocystis carinii from infected rat
      lungs.

PMID- 7804291
TI  - Phylogeny of Pneumocystis carinii based on beta-tubulin sequence.

PMID- 7804292
TI  - Accumulation of surfactant protein D in the lung during Pneumocystis carinii
      pneumonia.

PMID- 7804293
TI  - Production and characterization of monoclonal antibodies specific for the major
      surface glycoprotein of Pneumocystis carinii.

PMID- 7804295
TI  - Natural and structured baselines in the treatment of aggression following brain
      injury.
AB  - This single-case study describes the importance of presenting relevant baseline
      conditions in planning and evaluating treatment for aggression in a severely
      brain injured man 1 year after injury. An artificially low natural baseline
      resulted from staff reluctance to deliver instructions and corrective feedback
      needed for rehabilitation of self-care skill because these were frequently
      followed by aggression. A subsequent structured baseline presented these
      antecedents at the higher rates that were necessary for progress in the patient's
      rehabilitation. This resulted in an increase in aggressive behaviour, but also
      gave a more accurate representation of what his behaviour would be like under
      effective rehabilitation conditions. Intervention was based on data from the
      structured baseline, and included providing clear expectations, social
      reinforcement, and decelerative procedures. After reduction of aggression to
      zero, regular staff were reintroduced and presented instruction and corrective
      feedback as required. No further aggressive behaviour was noted, and self-care
      improved so that only minimal assistance was needed. Six months following
      reintroduction of regular staff, both baseline conditions were replicated. No
      aggressive behaviour was observed during either, suggesting that maintenance of
      gains could not be attributed to an artificially reduced rate caused by staff
      avoiding trigger antecedents.

PMID- 7804294
TI  - Oral physostigmine and impaired memory in adults with brain injury.
AB  - The purpose of this study was to examine the effects of physostigmine, a
      cholinergic agonist, on memory loss after traumatic brain injury (TBI), as
      compared to placebo or scopolamine, a cholinergic antagonist, using a double
      blind, placebo-controlled design. Each subject received each active drug and
      placebo. Neuropsychological measures (Wechsler Memory Scale I and II, Selective
      Reminding Test, Trail-Making Test, Parts A and B, Digit Symbol, and Memory
      Questionnaire) and measures of clinical balance were completed at baseline, after
      each drug phase, and at 1 month follow-up. Thirty-six subjects completed the
      study with results showing an improvement in memory scores in 44% of subjects
      (responders) while taking oral physostigmine. The most sensitive measure was the
      Selective Reminding Test, specifically Long-term Storage. The impact of drugs on
      standing balance as compared to placebo was improved standing time in the
      responders: (1) with physostigmine when standing tandem with eyes closed (p <
      0.05), and (2) with scopolamine when standing on one foot with eyes closed (p <
      0.05). Results support the potential benefit of cholinergic agonists on memory
      after TBI and the need for further research of possible clinical markers for the
      drug.

PMID- 7804296
TI  - Family functioning, social support and depression after traumatic brain injury.
AB  - Functional outcome after traumatic brain injury (TBI) is thought to be dependent
      upon effective social support and avoidance of depressive episodes. Research
      indicates that post-injury changes often occur in the family's functioning, hence
      impacting the family's ability to provide the needed social support. Social
      support, in turn, has been hypothesized to work as a buffer between significant
      life event and levels of depressive symptoms. Thus poor social support after a
      TBI, due to changes in family functioning, could result in depressive episodes
      for the person with a TBI. This paper empirically examines this question by
      investigating whether social support is predictive of depression in persons who
      have sustained a TBI. Thirty-nine persons who had sustained TBI were interviewed
      to assess their family functioning, perceived social support, and current
      depressive symptomatology. The results showed that the effective use of problem
      solving and behavioural coping strategies by the family in response to TBI was
      significantly related to lower levels of depression in the person who sustained
      the TBI. However, perceived social support was not predictive of depression.

PMID- 7804297
TI  - Swallowing difficulties and early CNS injuries: correlation with the presence of
      axial skeletal deformities.
AB  - We reviewed the neurological findings in 36 adults with history of perinatal
      brain injury that required gastrostomy due to progressive swallowing difficulties
      in a population of 624 institutionalized patients. A stereotypic pattern of
      progression of deficits was observed. Risk factors that correlated with increased
      risk of swallowing disorders included: presence of multiple handicaps;
      progressive deformities of the spine and extremities; decreased range of motion
      of mandible, laterognathism and other mandibular asymmetries. These findings
      suggest that spinal deformities and swallowing difficulties are part of a
      spectrum of impaired function of paired axial muscles in this population. The
      identification of these risk factors may help in the long-term care plan of
      severely impaired patients whose survival is extended by the use of feeding
      tubes.

PMID- 7804298
TI  - Agreement of classification decisions using two measures of motor co-ordination
      in persons with a traumatic brain injury.
AB  - Identification of motor co-ordination deficits in persons with a traumatic brain
      injury (TBI) is a vital part of both assessment and rehabilitation. The purpose
      of this study was to investigate the agreement of classification decisions based
      on clinical (subjective) and instrumented (objective) tests for measuring upper
      limb co-ordination in persons with a TBI. Twenty-two subjects with TBI performed
      the 'finger-to-nose' test and a 'lateral reach tapping test' 12 months post
      injury. After reduction to categorical form (deficit/no deficit), the data were
      interpreted using a generalized kappa statistic, to estimate the agreement
      between the two tests. The kappa values for the right and left upper extremities
      were 0.625 and 0.360, respectively, while the combined (right and left) value was
      0.500, representing only 'moderate' agreement between the two testing protocols.
      This indicates that motor co-ordination deficits in persons with TBI can be
      documented using either clinical or instrumented tests. The choice of test does
      not appear to be based on the subjective/objective nature (dimension) of each
      test, but rather on more practical factors such as administration time, cost and
      level of objectivity desired by the clinician.

PMID- 7804299
TI  - Persistent absence of auditory brainstem responses with preserved hearing and
      recovery from a prolonged comatose state.
AB  - A patient with hypertensive intracerebellar haemorrhage, who recovered from
      impending tonsillar herniation with emergency haematoma evacuation, showed
      persistent absence of auditory brainstem responses. The patient demonstrated a
      preserved stapedius reflex and hearing after recovery, indicating that the
      auditory brainstem pathway was not completely disrupted. We suggest that the loss
      of the auditory brainstem response (ABR) could be accounted for by impulse
      asynchrony along the auditory brainstem pathway. The existence of such a case
      implies that persistent absence of the ABR is not always indicative of
      irreversible brainstem damage and a poor outcome following severe brain injury.

PMID- 7804300
TI  - After traumatic brain injury: a discussion of consequences.
AB  - Traumatic brain injury is followed by many changes in cognition, emotion, social
      interaction and functioning, and communication. These changes may range from
      severe to subtle. They create complex difficulties for the individual and his or
      her network of support. Presented here is a review of the literature on the
      changes and their impact. The review comprises Part I, on brain injury and its
      effects, and Part II, on social interaction research.

PMID- 7804301
TI  - Whatever it takes: a model for community-based services.
AB  - The Whatever It Takes model is presented as an extension of the
      medical/rehabilitation model. It is not presented as an alternative to the
      rehabilitation model, although it does represent an opposition to the manner in
      which the model is typically implemented in community-based programmes for
      individuals with acquired brain injury. After brain injury, medical complications
      persist and a strictly anti-medical model in a community-based programme is
      unwise. On the other hand, community-based programmes that attempt to treat the
      individual, or provide rehabilitation services, in the absence of careful
      consideration of environmental barriers or the need for natural supports, are not
      likely to meet the long-term community reintegration needs of the individual, and
      may be unjustly using up finite resources. There are numerous complications
      associated with living with the effects of acquired brain injury. There also is
      considerable complexity associated with a health-care system and reimbursement
      system that emphasize acute care. Given these complexities, and the strong
      probability that a cure for brain injury is not likely to be found within the
      next decade, even the most learned professionals in brain injury are likely to
      say that practical solutions are needed for the present. Most notable is the late
      Dr Sheldon Berroll, who provided so much leadership to the field, but when asked
      about solving the day-to-day problems for an individual, would often respond: 'Do
      whatever it takes'. This advice was not presented in desperation, but rather as
      practical guidance. We have attempted to describe the whatever it takes approach,
      and to provide some guidelines for its implementation in community integration
      programmes.

PMID- 7804302
TI  - Beta 2-glycoprotein I.

PMID- 7804303
TI  - 6th International Symposium on Antiphospholipid Antibodies. Leuven, Belgium, 14
      17 September 1994. Proceedings.

PMID- 7804304
TI  - The annexins.

PMID- 7804305
TI  - Anticardiolipin antibodies: specificity and function.
AB  - Antibodies detected by solid phase anticardiolipin immunoassays are heterogeneous
      but understanding the nature of this heterogeneity has proven difficult.
      Differences in any of the following features may account for differences in
      anticardiolipin antibodies: avidity for cardiolipin, phospholipid cross
      reactivity, specificity for beta 2 glycoprotein I (beta 2GPI)-cardiolipin
      complexes, functional activity (as defined by the ability to inhibit phospholipid
      dependent coagulation reactions) and specificities for different conformations of
      phospholipids. Understanding these differences may be important in explaining the
      variations in clinical presentation of patients with these antibodies. This
      review attempts to define and discuss anticardiolipin heterogeneity.

PMID- 7804306
TI  - Inhibition of phospholipid-dependent coagulation reactions by 'antiphospholipid
      antibodies': possible modes of action.

PMID- 7804307
TI  - Protein C pathway, antiphospholipid antibodies and thrombosis.

PMID- 7804308
TI  - Physiology of membrane lipid asymmetry.

PMID- 7804309
TI  - Anticardiolipin antibodies in NZW x BXSB F1 mice.

PMID- 7804310
TI  - Antiphospholipid antibodies in an in vivo thrombosis model in mice.
AB  - The mouse model described in this study offers a unique method of determining the
      characteristics and mechanism(s) of action of aCL antibodies in thrombosis in
      vivo. In addition, this animal model enables the study of the kinetics of
      formation and dissolution of thrombus, as well as clot area, to be studied in a
      dynamic fashion. Other models for evaluation of thrombus formation rely on
      measurements of thrombus size and weight in ligated vessel segments where flow
      may be interrupted artificially. In addition, two important findings can be
      extracted from the study. (1) The size of the thrombi were significantly larger
      in mice that were passively immunized with IgG-APS (four patient samples
      examined) and with IgM-APS (two patient samples examined) compared with mice
      injected with saline or with immunoglobulin from control patients. (2) The clot
      persisted significantly for longer periods of time (total time) in animals
      injected with IgG-APS or IgM-APS when compared with control animals. Based on in
      vitro experiments, it is possible that these antibodies may inhibit protein C
      activation, neutralize the inhibitory activity action of beta 2 glycoprotein I
      (beta 2GPI), or activate platelets at the site of the femoral vein injury.
      Because this model enables to study the dynamics of thrombus formation, it is
      possible that these hypotheses and other mechanisms by which aPL antibodies are
      thrombogenic be investigated. Future studies will also include the effects of
      different levels of antibodies, as well as effects of affinity purified and
      monoclonal aPL antibodies on thrombus formation.

PMID- 7804311
TI  - Models for central nervous system complications of antiphospholipid syndrome.
AB  - One of the clinical hallmarks of antiphospholipid syndrome is the development of
      neurological complications, namely cerebral ischaemia, chorea, multi-infarct
      dementia, amaurosis fugax, migraine and transverse myelitis. An animal model
      should include the development of measurable neurological deficits and evidence
      of cerebral infarction. Although there are a number of mouse models for fetal
      loss, there has been no convincing model for the neurological complications of
      the antiphospholipid syndrome. One explanation for the high frequency of
      neurological events in antiphospholipid syndrome is a vulnerability of the
      cerebral vasculature to the hypercoagulable state associated with the syndrome. A
      greater appreciation of the differences in the regulation of coagulation between
      the systemic and cerebral vasculatures may be key to understanding the apparent
      predilection for central nervous system involvement in the antiphospholipid
      syndrome.

PMID- 7804312
TI  - Role of IL-3 in the antiphospholipid syndrome.
AB  - Antiphospholipid syndrome (APLS) is characterized by recurrent thromboembolic
      phenomena, thrombocytopenia and fetal loss. We describe various methods of
      induction of experimental APLS. These models were employed to study a variety of
      therapeutic agents including low dose aspirin, low molecular weight heparin, IVIG
      and thromboxane receptor antagonist. Because interleukin-3 (IL-3) is a
      multilineage cytokine affecting also megakaryocytes, is regarded as a 'good'
      cytokine in various stages of pregnancy and as low levels of IL-3 were recorded
      in APLS, it was logical to employ IL-3 as a therapy for APLS. Indeed, this
      treatment completely abrogated all the manifestations of experimental APLS.
      Furthermore, it was found that low dose aspirin most probably affect positively
      APLS via inducing an increased production of IL-3 by monocytes.

PMID- 7804313
TI  - Antiphospholipid antibodies and placental anticoagulant protein I.

PMID- 7804314
TI  - Antiphospholipid antibodies and endothelial cells.

PMID- 7804315
TI  - Antiphospholipid antibodies and eicosanoids.

PMID- 7804316
TI  - Thoughts on the mechanism of pregnancy loss associated with the antiphospholipid
      syndrome.
AB  - Although far from conclusive, the available clinical and histopathological
      information are consistent with an hypoxic cause for aPL-related fetal loss. In
      turn, this is due to impairment of the maternal spiral arterial blood flow. To
      date, there is only one case report of detailed placental and uteroplacental
      vascular histopathological examination by a recognized expert in this field of
      pathology. This and the findings provided by the only study to take placental bed
      biopsies suggest that spiral arterial vasculopathy resulting in placental and
      fetal hypoxia is the immediate cause of fetal loss in women with aPL syndrome.
      Data from the large study by Out et al. are consistent with this. The absence of
      spiral arterial vasculopathy in several studies could be attributed to the fact
      that the vessels examined were those adherent to the separated placenta, too
      superficial to necessarily demonstrate the pathological changes. Our future
      efforts at defining the 'cause' of aPL-related fetal loss must include: (1)
      meticulous clinical details regarding the timing and nature of pregnancy loss,
      (2) thorough evaluation of the abortus, (3) examination of the placenta by a
      pathologist well versed in placental pathology, (4) examination of the placental
      bed biopsies whenever possible, (5) the cellular biology and biochemistry of
      maternal-fetal junction, with particular focus on how the cytotrophoblast invades
      the spiral arteries, and (6) the cellular biology and biochemistry of spiral
      arterial vasculopathy.

PMID- 7804317
TI  - Assays for detection of antiphospholipid antibodies.

PMID- 7804318
TI  - Antiphospholipid syndrome within systemic lupus erythematosus.

PMID- 7804319
TI  - 'Primary', 'secondary' and other variants of the antiphospholipid syndrome.
AB  - Although the APS seen as a PAPS or accompanying SLE essentially manifests the
      same clinical features, there appears to be distinct differences in the two
      groups of patients which have been summarized in this article. Additionally, the
      fact that some patients with Sneddon's syndrome, Trousseau's syndrome, or even
      Addison's disease, may in reality be examples of aPL-related vascular occlusive
      events has opened new avenues, not only for identification of these patients, but
      also for more systematic therapeutic regimens.

PMID- 7804320
TI  - Stroke prevention in patients with antiphospholipid antibodies.

PMID- 7804321
TI  - Clinical trials on antiphospholipid syndrome: what is being done and what is
      needed?

PMID- 7804322
TI  - Antiphospholipid antibody: future developments.
AB  - In September 1991, an NIH workshop on molecular and biological aspects of
      antiphospholipid antibodies (aPL) identified questions for future studies: are
      the antibodies defined by the ELISA and by the lupus anticoagulant tests the
      same? Is aPL directly responsible for disease? What is the antigen? What drives
      the production of aPL? What is the role of beta 2-glycoprotein I? What accounts
      for patient heterogeneity? Can a satisfactory animal model be developed? The NIH
      workshop did not address important clinical questions, including those of
      pathogenesis and treatment. In 1994 many of these questions have at least partial
      answers. beta 2-glycoprotein I appears to be an obligatory component of the
      antigen, abnormal coagulation is the probable central pathogenic event and animal
      models now exist. There are still critical unknowns that define a future research
      agenda: the genetics of the aPL syndrome, the relationship of aPL to SLE and
      mechanisms of pathogenesis (including why clotting is episodic and what is the
      cellular or anatomical location of the initial injury). Despite a decade of
      clinical studies, risk prediction for defined patient groups is only now
      beginning to be studied. There are still almost no randomized, prospective,
      controlled treatment trials on any aspect of the syndrome nor are there
      definitive answers regarding which among antiplatelet, anticoagulant or
      antithrombin therapies is superior, what is the role of immunosuppressive therapy
      and what experimental therapies might be introduced. The molecular biology of the
      antigen-antibody interaction will soon be fully understood, then the cellular and
      the organism biology. Definitive treatment interventions may await this
      understanding but adequate therapies are available at this time to conduct
      important and effective prospective clinical trials.

PMID- 7804323
TI  - Phorbol ester induction of differentiation and apoptosis in the K562 cell line is
      accompanied by marked decreases in the stability of globin mRNAs and decreases in
      the steady state level of mRNAs encoding for ribosomal proteins L35, L31, L27,
      and L21.
AB  - To understand how phorbol ester induction switches the leukemia cell line K562
      from erythroid specific gene expression to an apparently irreversible program of
      megakaryocytic gene expression, we used a subtractive cDNA cloning strategy to
      identify cDNA sequence tags whose expression was suppressed after exposure of
      K562 cells to phorbol ester. The switch from the erythroid to megakaryocytic
      phenotype of K562 cells is due, at least in part, to marked decreases in the half
      lives of erythroid specific mRNAs. The phorbol ester induced decreases in the
      half-lives of erythroid specific mRNAs is reversed by cycloheximide or an
      inhibitor of protein kinase C. The phorbol ester induced shut off of cell
      division, and apparent terminal differentiation and apoptosis of K562 cells is
      also associated with a coordinate decrease in the expression of mRNAs that encode
      ribosomal proteins.

PMID- 7804324
TI  - The steady state levels and structure of the U7 snRNP are constant during the
      human cell cycle: lack of cell cycle regulation of histone mRNA 3' end formation.
AB  - The U7 small nuclear ribonucleoprotein (snRNP) is an essential component of the
      endonucleolytic cleavage reaction which leads to the production of mature 3'-ends
      of histone premRNAs. We have examined the relative amount and the structure of
      the U7 snRNP, as assayed by sensitivity to micrococcal nuclease, during the cell
      cycle in human HeLa and WI-38 cells. Using an RNase A protection assay, we find
      no change in the steady state levels of U7 throughout the cell cycle. Similarly,
      the sensitivity of U7 to micrococcal nuclease remained unchanged in both cell
      types. Contact inhibited WI-38 cells, that are deemed to have left the cell cycle
      and entered a quiescent state, displayed similar levels of U7 to cells in S and
      G1 phases of the cell cycle, however, the U7 snRNA was slightly more resistant to
      micrococcal nuclease. Histone 3' end mRNA processing was also assayed in HeLa
      cell cycle phase-specific extracts. In marked contrast to previous observations
      in extracts prepared from the rodent cell line, C3H10T1/2, (Hoffmann and
      Birnstiel, 1990), we find that the 3' end processing reaction remained constant
      throughout the cell cycle.

PMID- 7804325
TI  - Thyroid hormone regulation of Na,K-ATPase alpha 2 gene expression in cardiac
      myocytes.
AB  - Thyroid hormone (T3) stimulates Na,K-ATPase activity and alpha and beta subunit
      mRNA abundances in myocardial cells in vivo and in vitro. In this study, we used
      transient transfection and nuclear run-on assays to determine whether T3
      regulates the transcription rate of the Na,K-ATPase alpha 2 subunit gene. Primary
      cultures of neonatal rat cardiac myocytes were incubated with 100 nM T3 for 1, 3,
      and 6 d, and alpha 2 mRNA levels were measured by Northern blot hybridization
      analysis. There was no change in the abundance of alpha 2 mRNA by 1 d of T3
      treatment, whereas a two- and threefold increase in alpha 2 mRNA was evident when
      cells were exposed to T3 for 3 and 6 d, respectively. A portion of the rat alpha
      2 gene containing 1700 base pairs (bp) of 5'-flanking DNA sequence was isolated
      and fused to the firefly luciferase gene. Transient transfection experiments
      utilizing this chimeric gene showed no T3 trans-activation of reporter gene
      activity either in the absence or presence of cotransfected beta 1 or alpha 1
      isoforms of rat T3 receptor (T3R). In contrast, cotransfection of T3R facilitated
      a strong stimulation of luciferase activity driven by a construct containing a
      single copy of a palindromic T3 response element (TRE). Nuclear run-on analysis
      indicated that the rate of transcription of the endogenous alpha 2 gene was
      enhanced 1.2-fold at 3 d of T3 treatment, and was not regulated at either 1 or 6
      d. These results indicate that the T3-dependent increase in alpha 2 mRNA content
      at 6 d is mediated at a post-transcriptional level. Unexpectedly, we observed a
      T3-dependent three-to sixfold repression of alpha 2/luciferase expression in
      cardiac myocytes cotransfected with T3R. Deletion analysis of the 5' end of the
      alpha 2 gene revealed a negative TRE between nucleotides -354 and -100.

PMID- 7804326
TI  - Regulation of nonmuscle myosin light chain 3 gene expression in response to
      exogenous MLC3nm mRNA.
AB  - We have evaluated the regulation of the nonmuscle alkali myosin light chain
      isoform, MLC3nm, in mouse C2 myoblasts, in vitro. We altered the normal MLC mRNA
      profile of these cells, using stable transfection to introduce an exogenous pool
      of human MLC3nm mRNA. We used an isoform-specific, species-specific mouse MLC3nm
      cDNA probe to examine the response of the endogenous gene to the exogenous
      expression. At high cell density, expression of the endogenous mouse MLC3nm mRNA
      in transfectants is reduced to 50-70% of that in vector-transfected controls.
      These results suggest that a feedback mechanism operates in vitro, to regulate
      the size of the total MLC3nm mRNA pool. The down regulation of the mRNA for
      endogenous isoform is not detected at low cell density, suggesting that the
      mechanism may be density dependent and related to myoblast differentiation.

PMID- 7804327
TI  - Modulation of progesterone-induced Xenopus oocyte maturation by prostaglandins E1
      and E2.
AB  - Prostaglandins E1 (PGE1) and E2 (PGE2), the general local modulators or "local"
      hormones, were able to inhibit the progesterone-induced maturation of Xenopus
      oocytes in vitro, but could not induce maturation by themselves. This inhibition
      was observed on the sensitivity of the maturation process of the oocyte responses
      to progesterone, but not on the maximum response or responsiveness. The decreased
      sensitivity of oocytes to progesterone by prostaglandin E1 or E2 was evident in
      both the increased concentration of progesterone and the prolonged time required
      for the maturation of 50% of the oocyte. PGE1 and PGE2 did not appear to affect
      either the basal level or the progesterone-reduced cAMP level of oocytes.
      Microinjection of PGE1 or PGE2 into the oocytes had no effect on progesterone
      induced oocyte maturation, suggesting that other cell surface-mediated signaling
      events might be responsible for this modulatory effect of the progstaglandins.

PMID- 7804328
TI  - Bibliography of cellular and molecular biology research.

PMID- 7804329
TI  - In the hands of babes. A new report targets youth gun violence.

PMID- 7804330
TI  - Policy ... private-letter ruling regarding hospitals and PHOs.

PMID- 7804331
TI  - The incredible shrinking premium increase.

PMID- 7804332
TI  - Continuum of care ... definition for subacute care.

PMID- 7804333
TI  - Litigation ... hospitals' freedom to send patients to tertiary facilities for
      specialized care.

PMID- 7804334
TI  - Strategic planning ... Virginia hospitals are exploring or forming partnerships.

PMID- 7804335
TI  - Performance holds sway with executives' pay.

PMID- 7804336
TI  - Scoping out 1995. How experts see the health care year unfolding. Interview by
      Terese Hudson.
AB  - In this issue, we look at the business side of health care from two different
      vantage points. First, how will health care fare in 1995 in the context of the
      overall economy? We've gathered a panel of economic experts to make predictions.
      Their conclusions? In general, providers won't benefit from a probable upturn in
      the broader economy.

PMID- 7804337
TI  - Regional forecasts. Predicting the unpredictable.

PMID- 7804338
TI  - Money & management.

PMID- 7804339
TI  - The unfriendly giant. With reform's collapse, will states ever get ERISA off
      their backs?

PMID- 7804340
TI  - Growing pains. PHOs are surviving their formative years and moving on to bigger
      things.

PMID- 7804341
TI  - Those #!@% hospital bills!

PMID- 7804342
TI  - Straight A's? Report card tracks progress of combining two health systems.

PMID- 7804343
TI  - Family docs: it pays to be wanted.

PMID- 7804344
TI  - Mercy or murder? Postelection reality: Oregon copes with Death with Dignity Act.

PMID- 7804345
TI  - Clinical maneuvers. Clinical integration: the whys and hows of restructuring to
      create value.

PMID- 7804346
TI  - Romancing the server. One big happy network? Health care considers switch to
      client/server.

PMID- 7804347
TI  - Flu shots for the fast lane.

PMID- 7804348
TI  - Laurence Wellikson, M.D.

PMID- 7804349
TI  - The price of market power. Feds set to pore over the effects of health networks.

PMID- 7804350
TI  - Rethinking PHOs.

PMID- 7804351
TI  - Fundamentally flawed?

PMID- 7804352
TI  - Leukemia after chemotherapy for cancer.

PMID- 7804353
TI  - A comparison of 2 modes of administration of recombinant interleukin-2:
      continuous intravenous infusion alone versus subcutaneous administration plus
      interferon alpha in patients with advanced renal cell carcinoma.
AB  - PURPOSE: To compare 2 treatment modalities with recombinant Interleukin-2 (rIL-2)
      for patients with advanced Renal Cell carcinoma (RCC): continuous intravenous
      infusion (CIV) alone versus subcutaneous (s/c) rIL-2 + Interferon-alpha (IFN
      alpha). PATIENTS AND METHODS: Data have been collected on 425 patients with RCC,
      treated CIV rIL-2 alone, (225 patients), or rIL-2 by the s/c route (200
      patients). Patients receiving s/c rIL-2 also received s/c IFN-alpha both drugs
      being administered on an outpatient basis. Patients receiving CIV rIL-2 were
      treated as inpatients. Patient eligibility criteria were similar on all studies,
      and included patients with progressive, advanced disease, but with an ambulatory
      performance status. RESULTS: The overall response rate for the CIV schedules was
      not significantly different from the s/c regimens: 15% (95% confidence limits
      (CL) 10-20%) vs 20% (95%CL 14-26%) with 4% CR in both approaches. Durable
      responses were seen in both CIV and s/c schedules and there was no evidence of a
      significant difference in survival in multivariate analysis. There was however an
      important shift in the toxicity profile. The s/c regimens do not induce a
      clinically detectable capillary leak syndrome, which is the dose limiting
      toxicity for CIV regimens. CONCLUSION: Although the introduction of CIV regimens
      of rIL-2 was a major step forward compared to high-dose bolus, because most
      patients could be treated in a normal oncology ward, the s/c schedule of rIL-2 +
      IFN-alpha offers the possibility of outpatient (home) therapy, with no evidence
      of a reduction in efficacy.

PMID- 7804354
TI  - Muramyl peptides augment the in vitro and in vivo cytostatic activity of canine
      plastic-adherent mononuclear cells against canine osteosarcoma cells.
AB  - A tumor cytostasis assay was developed that measured the effect of the
      immunomodulator muramyl dipeptide (MDP) on the in vitro cytostatic activity of
      canine plastic-adherent mononuclear cells. Mononuclear cells were isolated from
      the peripheral blood of healthy Beagle donors and allowed to adhere to a 96-well
      microtiter plate. The adherent cell population was characterized by cell
      morphology, non-specific esterase staining, and flow microfluorometry to be
      approximately 42% monocytes, 49% lymphocytes, and 8% eosinophils. Canine plastic
      adherent mononuclear cells spontaneously caused cytostasis of D-17 canine
      osteosarcoma target cell proliferation. The spontaneous cytostatic activity of
      adherent mononuclear cells was significantly augmented by exposure to MDP or to
      lipopolysaccharide (LPS), with maximal cytostatic activity being observed after
      combined exposure to MDP and LPS. Mononuclear cell cytostasis toward D-17 canine
      osteosarcoma and A375 human melanoma cells was enhanced (P < 0.05) when normal
      dogs were administered liposome-encapsulated muramyl tripeptide
      phosphatidylethanolamine, a lipophilic derivative of MDP, by intravenous
      injection.

PMID- 7804355
TI  - Effects of anti-transforming growth factor-beta antibody and interleukin-2 in
      tumor-bearing mice.
AB  - In previous studies we found that the immunosuppression seen in mice bearing
      Herpes virus type 2-transformed (H238) fibrosarcoma was likely to be due to tumor
      derived transforming growth factor-beta (TGF-beta). In vitro experiments showed
      that interleukin-2 (IL-2) and antibodies against TGF-beta could significantly
      counteract TGF-beta-induced depression in lymphocytes. The present study was
      performed to determine if the administration of polyclonal anti-TGF-beta antibody
      and recombinant IL-2, alone or in combination, could inhibit H238 tumor
      progression in vivo and to investigate possible mechanisms of action. The tumor
      cells were injected s.c. at 1 x 10(6) cells/mouse and treatments were given 1-10
      days post-injection. In phase I, a total of 25,000 units of IL-2 (5,000
      units/injection) and/or 900 ng of anti-TGF-beta (100 ng/injection) were
      administered i.p. per animal. Phase II was conducted similarly, except that each
      mouse received a total of 127,500 units of IL-2, either with or without the same
      amount of antibody. No treatment-related toxicity was noted. Tumor volumes were
      monitored for 16-18 days after tumor implantation. The H238 tumors in treated
      mice from both both phases grew as rapidly as, or significantly faster than, in
      untreated controls. Significant enhancement of tumor growth was found in the
      groups given IL-2 as a single agent, regardless of total dose. The combination of
      the higher IL-2 dose with anti-TGF-beta resulted in more rapid tumor progression
      than in animals given the antibody alone. Relative spleen weights, peripheral
      blood leukocyte counts, and the chemiluminescent oxidative burst of phagocytes
      were significantly elevated in all tumor-bearing mice, whereas T cell response to
      mitogenic stimulation was depressed. However, the oxidative burst capacity of
      spleen (but not blood) cells and natural killer cell cytotoxicity were markedly
      lower in the treated groups compared to nontreated tumor-bearing controls. In
      contrast, plasma levels of tumor necrosis factor-alpha and IL-2 were
      substantially higher in the group given both modalities (phase II) compared to
      the other treated groups. These findings show that anti-TGF-beta antibody, both
      with and without low-dose IL-2 regimens, can be safely administered in vivo.
      However, tumor growth was not delayed by the treatment protocols used. The
      induction of hyporesponsiveness in certain cell types may account, at least
      partly, for the enhancement seen in tumor progression.

PMID- 7804356
TI  - High binding affinity chimeric anti-colorectal carcinoma antibody correlated to
      enhanced tumor binding and effector function.
AB  - The genetically engineered mouse/human chimeric cB72.3m4 and cB72.3m12 antibodies
      all recognized the tumor-associated TAG72 antigen. The high affinity cB72.3m4
      antibody had an approximately 18-fold higher affinity constant for the TAG72
      antigen than the low affinity cB72.3m12 antibody. The relationship amongst
      antibody binding affinity, tumor binding and effector functions was studied by
      using these two antibodies. The data showed that the high affinity cB72.3m4
      antibody was reactive with, on average, 15% more colon adenocarcinoma cells on
      tissue sections than the low affinity cB72.3m12 antibody, and it did not produce
      any cross-reactivities with various normal tissues. The high affinity cB72.3m4
      antibody was able to mediate more effective ADCC and CDC to the human ovarian
      cancer cells in vitro than the low affinity cB72.3m12 antibody. This study
      provides evidence that this high affinity chimeric cB72.3m4 antibody may be
      useful in both immunodetection and immunotherapy of cancer.

PMID- 7804357
TI  - Report on the 8th Maimonides conference on cancer research, February 22-26, Ein
      Gedi, Israel.

PMID- 7804358
TI  - What's the score?

PMID- 7804359
TI  - Thymidine kinases: the enzymes and their clinical usefulness.
AB  - Thymidine kinases (TK) convert thymidine, or deoxythymidine (dT) to the
      respective monophosphate. TK occurs in many different procaryotic and eucaryotic
      species and different TK isoenzymes are found within the same eucaryotic cell.
      One isoenzyme (foetal, cytoplasmic, TK1) is associated with cell division while
      the other (adult, mitochondrial, TK2) is cell cycle independent. The relative
      isoenzyme activities in a tissue thus reflect the fraction of proliferating
      cells. The gene encoding TK1 has been cloned for many species and regulation of
      its expression is known to be complex. Increases in TK activity appear to
      correlate with the presence of human neoplasia and disease progression and
      regression have been reported to correlate with TK levels in many cancer types.
      TK estimations in human lymphoproliferative diseases have implicated this enzyme
      as an early marker of maldifferentiation. TK levels may also be increased in non
      dividing mammalian cells infected with RNA or DNA viruses. Some virus encoded TK
      has been shown to differ biochemically, immunologically and in substrate
      specificity from the corresponding TK isoenzymes in target host cells thus
      facilitating the development of specific antiviral therapeutics. Further, TK1 in
      leukemic cells may differ biochemically from normal cellular TK1 such that tumor
      specific TK may provide a target for tumor detection and therapy. TK quantitation
      has conventionally been performed in assays of enzyme activity using radiolabeled
      (3H or 125I) nucleoside substrates. The development of TK1-specific, non
      radioisotope based immunoassays and the measurement of TK mRNA in tumour tissue
      using TK (DNA or RNA) probes may prove sufficiently valuable to be incorporated
      into the routine clinical management of human cancer.

PMID- 7804360
TI  - Clinical and preclinical evaluation of recombinant PEG-IL-2 in human.
AB  - High dose interleukin-2 alone or in combination with lymphokine activated killer
      (LAK) cells has demonstrated antitumor activity in a variety of malignant
      diseases. The currently formulated recombinant human interleukin-2 (IL-2) has
      limited solubility and short circulatory half life resulting in limited
      bioavailability. To improve the bioavailability of IL-2 the protein was
      covalently bound to activated Polyethylenglycol (PEG). We designed a phase I/II
      trial to evaluate the bioactivity of PEG-IL-2 in man, given as intravenous (iv)
      bolus injection every two weeks, and to determine safety, efficacy, and the
      maximum tolerated dose (MTD) in patients with advanced malignancies. Assessment
      of cytokine levels, phenotypic analyses and differential blood counts were
      performed to investigate the effects of PEG-IL-2 in-vivo. To compare in-vitro PEG
      IL-2 activity to activities of IL-2 we evaluated proliferation, cytotolytic
      activity, morphology, and phenotype of cytokine activated lymphocytes. Among
      seven patients treated with PEG-IL-2, there was no objective remission, three
      patients exhibited stabilisation of disease. Four patients presented with further
      disease progression. Treatment-related toxicity was mild to moderate (mainly WHO
      grades I and II) in patients receiving dose levels up to 10 x 10(6) IU/m2
      (maximum tolerated single dose in the outpatient setting). No toxic deaths
      occurred. In comparison to IL-2, the pharmacokinetic profile of PEG-IL-2
      exhibited increased plasma levels and a decreased clearance (alpha and beta half
      life estimates of 4 and 14 hours, respectively). The analysis of a variety of
      immunologic parameters demonstrated that PEG-IL-2 has significant biologic
      activity both in vitro, and in man.

PMID- 7804361
TI  - Successful in vivo generation of canine lymphokine-activated killer cells by
      continuous recombinant interleukin-2 infusion through the splenic artery.
AB  - We studied the efficacy of infusing human recombinant interleukin-2 (IL-2)
      through the splenic artery for generation of lynphokine activated killer (LAK)
      cells in vivo in a canine system. Catheters were inserted into the splenic
      artery, portal vein and inferior vena cava (IVC) in Beagle dogs. IL-2 was
      administered continuously through either the splenic artery or IVC by portable
      infusion pump and the cytotoxic activity of portal vein blood lymphocytes (PVBL)
      and peripheral blood lymphocytes (PBL) against canine osteosarcoma D-17 target
      cells was monitored. Following administration low-dose IL-2 (8 x 10(5) IU/day)
      for 6 days through the splenic artery, LAK precursor cells were present, but not
      following administration intravenously. Interestingly, when a high dose of IL-2
      (4 x 10(6) IU/day on days 1-6 and 13-18) was administered through the splenic
      artery, strong cytotoxicity was detected in PVBL and PBL without subsequent
      culture in vitro with IL-2, suggesting that an infusion rate of 4 x 10(6) IU/day
      IL-2 may be sufficient for generation of LAK cells in vivo. These results suggest
      that continuous infusion of IL-2 through the splenic artery can generate LAK
      cells more easily and may prove especially useful for the immunotherapy of
      hepatic micrometastasis.

PMID- 7804362
TI  - Treatment of transitional cell carcinoma of the bladder with intravesical
      interleukin-2: a pilot study.
AB  - Human recombinant interleukin-2 (rIL-2) administered systemically can mediate the
      regression of solid tumors in some patients. IL-2 has been detected in the
      bladder effluent from patients treated with intravesical BCG for transitional
      cell carcinoma of the bladder (TCC), suggesting that IL-2 may be an effector
      molecule in the mechanism of action of BCG. The purpose of the pilot study was to
      determine the response rate, duration of response and toxicity of rIL-2 (Cetus)
      administered intravesically to previously untreated patients and patients who had
      failed prior intravesical therapy with other agents. Fourteen patients with
      biopsy proven transitional cell carcinoma (13 Stage TIS/Ta/T1, 1 Stage T2) were
      treated with 8 weekly instillations of 12 x 10(6) IU of rIL-2. An index lesion
      was followed with cystoscopy, biopsy and cytology at three months, with identical
      follow up every three months thereafter if a response was noted in the index
      lesion at the first evaluation. There were 3 complete responses (duration of
      response measured from start of treatment to date of progression) of 9+, 3, 9
      months; one patient with TIS, and 2 patients with Ta disease. There were 11 non
      responders for an overall response rate of 21%. One patient with extensive CIS
      had a dramatic partial response and was converted to a complete response with a
      second 8-week course of rIL-2. All of the complete responders had failed prior
      intravesical therapy with standard agents. Toxicity from rIL-2 given
      intravesically was minimal. One patient reported malaise for 24 hours after each
      treatment and two patients developed asymptomatic lower UTIs.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7804363
TI  - Sustained oral indomethacin and ranitidine with intermittent continuous infusion
      interleukin-2 in advanced renal cell carcinoma.
AB  - Experimental work in murine models has shown that, during the development of
      tumors, prostaglandin E2 produced by host macrophages inactivates natural killer
      cells and suppresses lymphokine-activated killer (LAK) cell development. Chronic
      indomethacin therapy when combined with interleukin-2 (IL-2) can totally
      eradicate experimental lung metastases in these models. A phase II trial was
      performed to study the clinical efficacy of chronic indomethacin and intermittent
      IL-2 therapy in patients with advanced renal cell carcinoma. Patients were placed
      on indomethacin and ranitidine orally at least one week prior to commencing
      therapy with IL-2. IL-2 was given by continuous infusion for three courses, each
      consisting of 5 days of treatment with 6 days of rest. Initial dose of IL-2 was
      18.0 x 10(6) IU/m2/day for the first course with escalation to 27.0 x 10(6)
      IU/m2/day for the second and 36.0 x 10(6) IU/m2/day for the third course, if
      toxicity allowed. Patients were admitted to a general oncology ward for therapy
      with IL-2, and vasopressor agents were not used. Thirty-two patients were
      eligible, with 7 patients withdrawing early from the study. Twenty-five patients
      went on to receive at least one course of IL-2. Two complete and three partial
      responses were seen for an objective response rate of 5/25 (20%) for eligible and
      treated patients or 5/32 (16%) for all patients entered onto the study,
      regardless of treatment status. The response rate to this regimen is comparable
      with other high dose IL-2 regimens in renal cell carcinoma, including those
      employing adoptive therapy with lymphokine-activated killer cells.

PMID- 7804364
TI  - Chromosomal changes during the acquisition of resistance to adriamycin in
      tumorigenic human synovial cells.
AB  - Chromosome analysis of tumorigenic human synovial cells at different stages of
      acquisition of resistance to doxorubicin was undertaken. Exposure of the
      sensitive cells to adriamycin for 2h induced chromatid aberrations, while
      exposure to the drug for 6h did not show any mitosis. However, drug resistant
      cells continued to show high frequency of mitosis even in presence of the drug.
      High frequency of chromatid exchanges were seen during the process of the
      development of drug resistance by exposure to increased drug concentration.
      Double minutes, a characteristic feature of resistant cells appeared only when
      the drug resistance was established in the cells, which was confirmed by drug
      sensitivity assay.

PMID- 7804365
TI  - Increased oxygen tensions modulate the cellular composition of the adaptive
      immune system in BALB/c mice.
AB  - In acute and chronic experiments, each of eight groups of young mice were
      assigned separately to different pressures of oxygen to which it was to be
      exposed. Lymphocytes from spleen, thymus, and peripheral blood were analyzed
      following oxygen exposure. Subset populations changed depending on the oxygen
      tension. Blood lymphocyte populations reflected lymphocyte changes in thymus or
      spleen. Thus, a full understanding of the pharmacological effects of hyperbaric
      oxygen, requires a knowledge of simultaneous effects of increased oxygen
      pressures on the various compartments comprising the immune system.

PMID- 7804366
TI  - The tyrosine residue at position 97 in the VH CDR3 region of a mouse/human
      chimeric anti-colorectal carcinoma antibody contributes hydrogen bonding to the
      TAG72 antigen.
AB  - One amino acid, tyrosine at position 96 and 97 in the VH CDR3 region of a
      mouse/human chimeric anti-TAG72 antibody cB72.3m4 was substituted by the
      phenylalanine residue and by a number of amino acids from different amino acid
      groups by the site-directed mutagenesis technique. The expression vector mpSV2neo
      EP1-Vm11-16C1 containing mutant VH region fragments (Vm11-16) as well as the
      immunoglobulin enhances (E), promoter (P1) and the human genomic C1 region
      fragments, were transfected into a heavy-chain-loss mutant cell line B72.3Mut(K),
      respectively. Mutant chimeric cB72.3m11-16 antibodies were purified from the
      transfectant supernates and compared based upon their binding affinity for the
      TAG72 antigen relative to that of the original cB72.3m4 antibody. The data showed
      that a single amino acid substitution of tyrosine by phenylalanine and a number
      of amino acids including serine, asparagine, histidine and arginine at position
      97 in the VH CDR3 region all resulted in approximate 18-fold lower binding
      affinity, whereas the substitution of tyrosine by phenylalanine at position 96 in
      the VH CDR3 region did not affect the binding affinity of the cB72.3m4 antibody.
      This suggests that the tyrosine residue at position 97 in the VH CDR3 region is
      in a contact position in the B72.3/TAG72 antibody/antigen interaction, and that
      the terminal hydroxyl group of the position 97 tyrosine side-chain contributes
      hydrogen bonding to the TAG72 antigen, whereas the position 96 tyrosine side
      chain does not.

PMID- 7804367
TI  - Protective effect of gypenosides against oxidative stress in phagocytes, vascular
      endothelial cells and liver microsomes.
AB  - The action of gypenosides (GP, saponins of Gynostemma pentaphyllum, a Chinese
      medicinal herb) as an antioxidant was studied using various models of oxidant
      stress in phagocytes, liver microsomes and vascular endothelial cells. The
      results show that GP decreased superoxide anion and hydrogen peroxide content in
      human neutrophils and diminished chemiluminescent oxidative burst triggered by
      zymosan in human monocytes and murine macrophages. An increase of lipid
      peroxidation induced by Fe2+/cysteine, ascorbate/NADPH or hydrogen peroxide in
      liver microsomes and vascular endothelial cells was inhibited by GP. It was also
      found that GP protected biomembranes from oxidative injury by reversing the
      decreased membrane fluidity of liver microsomes and mitochondria, increasing
      mitochondrial enzyme activity in vascular endothelial cells and decreasing
      intracellular lactate dehydrogenase leakage from these cells. The extensive
      antioxidant effect of GP may be valuable to the prevention and treatment of
      various diseases such as atherosclerosis, liver disease and inflammation.

PMID- 7804368
TI  - Disclosure in research funding.

PMID- 7804369
TI  - The impact of interleukin-2 on survival in renal cancer: a multivariate analysis.
AB  - The purpose of this analysis was to compare the survival of patients with
      advanced renal carcinoma treated with intravenous recombinant interleukin-2 to
      the survival of matched patients taken from the large and well characterised
      database of the Eastern Cooperative Oncology Group (ECOG). Recombinant
      interleukin-2 (rIL-2) given by continuous intravenous infusion was used to treat
      387 patients with advanced adenocarcinoma of the kidney in five multi-centre
      studies and 327 of these patients fulfilled the study eligibility criteria and
      were evaluable for response, toxicity and survival. The survival of patients
      treated with rIL-2 was compared in a multi-variate survival analysis taking
      account of all identified prognostic factors to 390 control patients receiving
      chemotherapy derived from the database. Thirteen patients treated with rIL-2
      achieved a complete remission of their disease and 32 a partial remission giving
      an overall response rate of 14%. Remissions were durable with a median duration
      of 357 days for partial remissions and a median duration in excess of 926 days
      for complete remissions. Most patients experienced fever or mild to moderate
      hypotension and other toxicities are described. However, only 11 patients
      required admission to intensive care and in only five cases was this judged to be
      due to treatment toxicity. There were three deaths judged to be probably due to
      treatment toxicity. rIL-2 treatment was associated with significantly prolonged
      survival compared to the ECOG control patients. Patients with good prognostic
      features appeared to have a greater survival benefit from rIL-2 than those with
      poor prognostic features. This analysis provides the first evidence that rIL-2
      prolongs survival in patients with advanced renal cancer but cannot provide proof
      which should be sought in randomised prospective trials drawing on the hypotheses
      generated herein.

PMID- 7804370
TI  - Subcutaneous recombinant interleukin-2 and alpha-interferon in patients with
      advanced renal cell carcinoma: results of a multicenter Phase II Study.
AB  - A phase II multiinstitutional clinical trial was conducted to evaluate the safety
      and efficacy of the subcutaneous outpatient administration of recombinant human
      interleukin-2 and alpha-interferon in patients with progressive metastatic renal
      cell carcinoma. One hundred and forty-five patients were entered on this study
      between October 1989 and May 1991. Among 134 patients evaluable for treatment
      response, there were six complete (4.5%) and twenty partial (14.9%) responders,
      with an overall response rate of 19.4% (95% confidence interval, 13-26%). The
      median duration of complete remissions was 228 (range 51(+)-520+) days; the
      median duration of partial tumor regressions was calculated at 226 (range 112
      473+) days. The overall median survival from start of therapy was 14.2 (range 1
      23+) months. Fever, chills and general fatigue occurred in the majority of
      patients treated and were measured at grade II, III and IV in up to 55%, 24% and
      3% of all evaluable patients, respectively. Three patients each developed grade
      III hypotension, dyspnea and diarrhea; two patients each had grade III and grade
      IV elevations of alkaline phosphatase; two and one patients respectively,
      exhibited grade III anemia and grade IV thrombocytopenia; two patients
      experienced severe cutaneous toxicity. The majority of patients received
      treatment in the outpatient setting. In summary, the outpatient use of
      subcutaneous interleukin-2 and alpha-interferon was effective in patients with
      advanced metastatic renal cell carcinoma; it was associated with less toxicity
      and thus, could improve the therapeutic index of interleukin-2 based biologic
      therapy when compared against high dose intravenous therapy.

PMID- 7804371
TI  - Limited efficacy of interferon-alpha and vinblastine as second line
      biochemotherapy regimen in patients with progressive metastatic renal cell
      carcinoma.
AB  - We report on thirty-four patients with metastatic renal cell carcinoma who were
      treated with a combination of subcutaneous recombinant interferon-alpha and
      intravenous vinblastine upon progression after previous antineoplastic therapy.
      Pretreatment included chemotherapy (n = 3), hormonal therapy (n = 6) and
      immunotherapy (interleukin-2/interferon-alpha, n = 25). In this study, treatment
      courses consisted of subcutaneous doses thrice weekly of recombinant interferon
      alpha at 6 million U/m2 (20 patients, group 2), respectively. Treatment was given
      over 8 consecutive weeks. Additionally, in all patients, vinblastine was
      administered intravenously at a dose of 6 mg/m2 in weeks 2, 5 and 8. Of 14
      patients treated in group 1, one had a partial response for 6 months (overall
      response rate 7.14%; 95% confidence interval, 0.18-33.87%), and four had disease
      stabilization (median duration, 5.0 months). Of 20 patients treated in group 2,
      there was one patient who achieved a complete response (response duration, 34+
      months); in addition, two patients had a partial response (median response
      duration, 10.5+ months; overall response rate, 15%; 95% confidence interval 3.21
      37.89%), and 13 patients exhibited disease stabilization (median duration 5.9+
      months). Response rates showed no significant differences when comparing
      treatment results in patients in group 1 vs group 2. In contrast, significantly
      less patients treated in group 2 had progressive disease (p = 0.024), as compared
      to patients in group 1. This treatment combination was overall well tolerated
      with low to moderate systemic toxicity. In addition, there were no significant
      differences in frequency or intensity of therapy-related systemic toxicities when
      comparing patients in group 1 and group 2, respectively.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7804372
TI  - Cytokine production and immune cell activation in melanoma patients treated with
      liposomal muramyl tripeptide (CGP 19835A lipid).
AB  - We conducted a pilot study using liposome-encapsulated muramyl tripeptide
      phosphatidylethanolamine (L-MTP-PE) preoperatively in patients with stage III or
      IV resectable melanoma who were at high risk for recurrence. Patients received L
      MTP-PE for 1 month before surgery and then 5 months postoperatively. Several
      immune parameters were monitored during preoperative therapy to search for
      correlations with clinical (tumor) response. The 18 patients were classified into
      three groups according to their responses and disease-free intervals: no evidence
      of disease (NED) at week 24 of therapy, relapse during therapy and progressive
      disease on therapy noted at the time of surgery. Six of nine patients in the NED
      group demonstrated increased monocyte tumoricidal activity (MTA) during week 1 of
      therapy. MTA increased in three of the six patients in the relapse group. MTA did
      not increase in the three patients who had progressive disease on therapy. Plasma
      neopterin levels were elevated by 72 h following the first L-MTP-PE dose in all
      18 patients. Circulating levels of tumor necrosis factor were elevated in 15 of
      16 patients tested, and IL-6 levels were elevated in all 18 patients. Melanoma
      cells from all three patients with progressive disease at the time of surgery
      proliferated well in vitro, whereas tumor cells from 10 of the 15 patients in the
      other two groups did not proliferate. There were no discernible differences among
      the three groups in the magnitude of IL-2-induced proliferation of tumor
      infiltrating lymphocytes. However, IL-2-activated TILs from the NED group
      exhibited cytotoxicity against autologous tumor cells in vitro. In summary,
      whereas L-MTP-PE stimulated several immunologic responses in all patients, the
      only two parameters that correlated with clinical status were MTA and the tumor
      proliferation assay. These two biologic assays could serve to distinguish
      potential responders from nonresponders early in the course of treatment.

PMID- 7804373
TI  - Enhanced activity against syngeneic murine tumors by intrasplenic injection of
      recombinant interleukin-2 (IL-2) and interleukin-1 (IL-1).
AB  - The antitumor activity of Interleukin-1 (IL-1), was assessed against the murine
      adenocarcinoma colon 26 tumor model in combination with Interleukin-2 (IL-2).
      Colon 26 tumor cells were inoculated on the back of syngeneic BALB/c mice.
      Fourteen days after inoculation, when the tumor nodule reached approximately 10
      mm in diameter, tumor nodules were resected and Hank's solution, IL-2, IL-1, or
      IL-2 plus IL-1 were injected directly into the mouse spleen. One week after
      treatment, potent natural killer (NK) and enhanced lymphokine activated killer
      (LAK) cell activities were seen in the splenocytes treated by the combination of
      IL-2 plus IL-1. Furthermore the combination treatment by IL-2 plus IL-1 resulted
      in a significantly prolonged survival. Phenotypic analysis showed an increased
      number of percent positive cells expressing asialo GM 1 and IL-2 receptor after
      treatment with IL-2 plus IL-1. A possible role of IL-1 in augmentation of IL-2
      dependent antitumor activity in vivo is discussed.

PMID- 7804376
TI  - [Risk of ovarian cancer in women treated for infertility].

PMID- 7804375
TI  - Protective effects of crocetin on the bladder toxicity induced by
      cyclophosphamide.
AB  - Cyclophosphamide (CX) has been widely used as an anticancer agent, however
      obtaining a maximum therapeutic potential for CX has remained a challenge, for
      generating undesired toxic side effects to the bladder. Crocetin, a natural
      carotenoid has been employed in the present studies to ameliorate the bladder
      toxicity of CX. Interestingly, crocetin at a dose of 50 mg/kg modulated the
      release of chloroacteldehyde, a urotoxic metabolite of CX in the urine of mice
      given combined treatment. Crocetin at the same dose significantly elevated
      Glutathione-S-Transferase enzyme activity both in the bladder and the liver of
      mice treated with CX. The exact mechanism of the protective effect of crocetin is
      not known, presumable it may act as an antioxidant, trapping and scavenging free
      radicals during the detoxification process. In Sarcoma-180 tumor bearing mice,
      crocetin has the ability to protect against CX induced bladder toxicity without
      altering its antitumor activity. Our studies are important to identify
      antioxidant rescue agents to overcome dose-limiting toxicity of CX.

PMID- 7804374
TI  - Recombinant bifunctional molecule FV/IFN-gamma possesses the anti-tumor FV as
      well as the gamma interferon activities.
AB  - Recombinant DNA techniques were used to clone, construct and express the
      bifunctional molecule FV/IFN-gamma. The FV/IFN-gamma is a single-chain 42KD
      fusion protein expressed in E. coli under control of the strong T7 bacteriophage
      promoter in the expression vector pT7-7-FV-IFN-gamma. The fused gene fragment FV
      IFN-gamma containing a single-chain anti-TAG72 FV gene fragment as well as the
      human recombinant cDNA fragment of IFN-gamma molecule. The renatured soluble form
      of FV/IFN-gamma was purified from E. coli inclusion bodies using HTPT
      chromatography. The yield of this fusion protein was estimated at 10mg/L. Our
      data showed that the FV/IFN-gamma molecule retained the TAG72 antigen-binding
      specificity and the IFN-gamma activity as measured in ELISA, Western blotting and
      up-regulation of CEA expression by IFN-gamma. Therefore, it may prove to be
      useful in targeting the biological effect of IFN-gamma to tumor cells and
      stimulating its immune destruction.

PMID- 7804377
TI  - [Treatment of impotence].

PMID- 7804378
TI  - [Update on prostate ultrasonography].

PMID- 7804379
TI  - [Does the endocrinal milieu influence the expression and/or the action of ovarian
      growth factors in polycystic ovary syndrome?].
AB  - Polycystic Ovary Syndrome (PCOS) results from endocrine, paracrine and autocrine
      dysfunction, affecting thecal and granulosa cells. The circulating insulin/IGF
      system is often dysregulated in PCOS. It could influence the local IGFs/IGF-BPs
      system, when granulosa, and more putatively thecal cells depend on. It is a new
      field of research about the physiopathology of PCOS, lying on clinical grounds.
      However, its practical interest is still limited.

PMID- 7804380
TI  - [Application of confocal laser microscopy in studying the effect of epidermal
      growth factor on the seminiferous epithelium].
AB  - Effects of epidermal growth factor (EGF) on pH transients in aggregates of
      Sertoli cells and germinal cells have been investigated with confocal microscopy
      using a fluorescent pH sensitive indicator. In some Sertoli cells EGF caused a
      rapid rise in the pH whereas other Sertoli cells did not respond to EGF. Some
      Sertoli cells showed a delayed response which coincidated with a similar pH
      change in neighbouring germinal cells. Since isolated germinal cells never showed
      a pH response after exposure to EGF, we have concluded that some Sertoli cells
      may communicate with germinal cells via gap junctions.

PMID- 7804381
TI  - [Genetic control of cellular differentiation and proliferation during
      gametogenesis in mammals].
AB  - Understanding the genetic program that controls the regulation of cells
      progressing through the mitotic and meiotic cell cycles, whether in response to
      growth factors, other extracellular signals, or intrinsic programs, is critical
      to problems in infertility and in gonadal neoplasias. In this study, we present a
      consideration of important stages of cell cycle control in mammalian germ cells
      and data illustrating the experimental approaches that can be used to determine
      the pattern of such genes which may be involved in these events.

PMID- 7804382
TI  - [Cytokines and Sertoli cell and germ cell interactions].
AB  - The seminiferous epithelium is a source for several cytokines. Interleukins (IL-1
      and IL-6) have been identified in Sertoli cells and more recently in germ cells.
      Their expression is modulated during the seminiferous epithelium cycle, via
      phagocytosis of residual bodies. Both IL-1 and IL-6 play a role in the
      replication of meiotic DNA and therefore intervene in the spermatogenetic
      process. The identification of other cytokines and the elucidation of their
      interaction with the cells of the seminiferous epithelium, should improve our
      knowledge of the male reproductive function and of the origin of some
      sterilities.

PMID- 7804383
TI  - [Cytokines and the corpus luteum].
AB  - This minireview present main findings concerning the contribution of cytokines to
      the regulation of some key processes of luteal functions. Data concerning the
      preovulatory follicles invasion by white blood cells and the migration of
      macrophages, granulocytes and T lymphocytes into corpus luteum suggest that local
      secretion of regulatory cytokines may be involved in regulating corpus luteum
      formation and demise as well its maintenance in early pregnancy. Several lines of
      evidence indicate that the pro-inflammatory cytokines such as IL-1, IL-6 and TNF
      alpha modulate the steroidogenic changes which take place during luteinization.
      For instance, an inhibition of E2 biosynthesis is evidenced in granulosa cells in
      human or porcine species with IL-1, in rat with TNF-a and in bovine with IL-6.
      Moreover, IL-1 stimulates P4 production but to a much lower extent than LH, and
      PGE2 synthesis by rat thecal cells. The potential relevance of pro-inflammatory
      cytokines in the mechanisms controlling luteolysis is suggested by the ability of
      IL-1 and TNF-alpha to decrease both P4 production and the survival of bovine
      luteal cells. As opposed to ruminants, TNF-alpha has no effect in human luteal
      cells but potentiates the decrease of P4 secretion induced by IFN-gamma. Finally,
      data regarding the participation of trophoblast interferons in the mechanisms for
      maintaining the corpus luteum at the establishment of pregnancy are now available
      in ruminants. From these observations and others, we can consider that cytokines
      are involved in the regulation of the corpus luteum function.

PMID- 7804384
TI  - [Growth factors: from oocyte maturation to blastocyst].
AB  - Developmental arrests and losses of viability are observed in vitro, when embryos
      are cultured. A harmonious oocyte maturation is essential to obtain a balanced
      development. Factors that control this maturation are still unknown but growth
      factors seem to be involved: they are present in ovary and some of them (EGF, TGF
      alpha, TGF-beta, PDGF) improve in vitro maturation. These factors are also
      involved in preimplantation development, either in an autocrine way (ligand and
      receptor genes expression in the embryo) or in a paracrine way (receptor gene
      expression in the embryo and ligand gene expression in the tractus). However, the
      precise role of each one and their interrelations are still speculative.

PMID- 7804385
TI  - [Antimullerian hormone in clinical human applications].
AB  - Anti-Mullerian hormone (AMH) is synthesized by immature Sertoli cells and by
      postnatal granulosa cells. Assay of serum AMH is useful in clinical situations to
      search for the presence of testicular tissue or to assess its functional value
      before puberty. At the time of puberty, serum levels of AMH decrease
      dramatically, a negative correlation has been demonstrated between AMH and
      testosterone serum levels. AMH assay is also useful in a rare form of male
      pseudohermaphroditism, characterized by the persistence of uterus and tubes in an
      otherwise normally virilized patient. AMH levels are undetectable or severely
      decreased in the case of a mutation of the AMH gene itself. In contrast, the
      concentration of serum AMH is normal if the syndrome is due to an insensitivity
      of AMH target organs.

PMID- 7804386
TI  - The cardiovascular effects of bupropion and nortriptyline in depressed
      outpatients.
AB  - The cardiovascular effects of bupropion hydrochloride and nortriptyline were
      compared in a double-blind, randomized, 6-week trial in adult outpatients with
      major depression. After a 1-week placebo phase, 58 patients were randomized to
      treatment with bupropion (225-450 mg/day) and 57 to nortriptyline (75-150
      mg/day). Nortriptyline-treated patients had statistically significant heart rate
      increases at each assessment as determined by RR intervals on electrocardiogram
      (14.5-18 bpm). Bupropion-treated patients had small but statistically significant
      increases in supine diastolic blood pressure of 5.6 mm Hg on day 7 and 7.5 mm Hg
      on day 28. A few patients in each treatment group had orthostatic changes, but
      only nortriptyline-treated patients had symptomatic orthostatic hypotension. A
      slowing of cardiac conduction and possibly of rate-corrected repolarization
      occurred in patients treated with nortriptyline that did not occur in patients
      treated with bupropion. Compared to nortriptyline, bupropion appears to have a
      wider safety margin with regard to cardiovascular effects. This may be
      particularly true in the elderly, in patients with preexisting cardiovascular
      disease, or in overdose.

PMID- 7804387
TI  - A review of studies of psychiatric factors in Crohn's disease: etiologic
      implications.
AB  - Researchers have recently challenged long-held concepts of psychological origins
      to inflammatory bowel disease, in particular with ulcerative colitis. The purpose
      of this paper is to review published studies on psychiatric factors in Crohn's
      disease to determine whether available evidence points to the absence or presence
      of a significant relationship between Crohn's disease and stressful life events
      or psychiatric symptoms or disorders. Twelve articles with > or = 10 subjects on
      which statistical data were reported from standardized instruments of measure
      were found. Most reported a significant association between Crohn's disease and
      psychiatric factors. Many of the investigative groups reporting such an
      association in Crohn's disease had also studied ulcerative colitis and failed to
      find a similar association in that disease. Published data indicate that Crohn's
      disease, unlike ulcerative colitis, may be statistically associated with lifetime
      psychiatric disorders. This association appears to be more modest than in
      irritable bowel syndrome, in which far higher rates of psychiatric disorders are
      reported than in Crohn's disease.

PMID- 7804388
TI  - Comparison of personality disorders in different anxiety disorder diagnoses:
      panic, agoraphobia, generalized anxiety, and social phobia.
AB  - Recently there has been increasing interest in the relationship of the
      personality and the anxiety disorders. This paper presents comorbidity findings
      between DSM-III-R personality pathology and several DSM-III-R anxiety disorders
      and makes direct comparisons between anxiety groups. This is the most extensive
      comparison of this kind reported thus far. This report is on the first 475
      anxiety patients who were recruited from multiple sites to take part in a
      naturalistic study of anxiety. All had a DSM-III-R diagnosis of panic,
      agoraphobia, social phobia, or generalized anxiety disorder (GAD). Previous
      studies which found a high comorbidity between the anxiety and the personality
      pathology were confirmed, with a significantly higher prevalence of personality
      pathology occurring with social phobia and GAD. Among our patients, all of whom
      had anxiety disorders, the presence of comorbid major depression is associated
      with an increase in the levels of comorbid personality pathology--as previously
      described in the literature. The relationship between low social functioning and
      the presence of personality pathology was confirmed, however, the relationship
      appears to be specific to certain areas of functioning, a new finding. There is a
      clinically important relationship between Personality Diagnostic Questionnaire-
      Revised personality pathology and the anxiety disorders characterized by
      different prevalences of personality disorders in different anxiety disorders and
      specific areas of social dysfunction.

PMID- 7804389
TI  - Clozapine treatment of polydipsia.
AB  - A patient with refractory chronic schizophrenia having severe polydipsia and
      hyponatremia was treated with clozapine. There followed a dramatic improvement in
      the polydipsia and correction of the hyponatremia. This improvement has been
      sustained throughout a 6-month follow-up.

PMID- 7804390
TI  - Transferring psychiatric patients into managed care networks.
AB  - The practice of selective contracting in managed care organizations has caused
      frequent transfers of psychiatric patients from emergency rooms and hospitals
      that have been excluded from provider networks. Psychiatrists and other
      physicians who do not participate in these networks may be reluctant to transfer
      patients into unfamiliar clinical arrangements simply at the request of insurance
      companies. Possible reasons for such resistance include an unwillingness of
      physicians to disrupt treatment once it has begun, concerns about the risk of
      injury while transporting psychiatric patients, and the need to stabilize
      patients prior to transfer. Although fears of patients injuring themselves or
      others in transit appear to be unwarranted, certain clinical and risk management
      issues merit further consideration by HMOs and managed care organizations.

PMID- 7804391
TI  - Multiple serotonin receptors: clinical and experimental aspects.
AB  - Serotonin (5-hydroxytryptamine; 5-HT) has been implicated in a large number of
      psychophysiologic processes including the regulation of sleep, appetite, mood,
      aggression, perception, memory, and anxiety. To mediate this large array of
      physiologic processes, at least 14 separate 5-HT receptors have evolved, which
      are divided into seven main families. Not surprisingly, alterations of 5-HT
      receptor activity have been shown to occur in many psychiatric diseases including
      anxiety, depression, eating disorders, schizophrenia, personality disorders, and
      many drug-induced psychotic states. Additionally, a number of effective
      psychopharmacologic agents for diseases as diverse as schizophrenia and anxiety
      have been developed which either specifically alter brain levels of serotonin or
      bind to 5-HT receptor subtypes. This review article summarizes recent advances in
      the burgeoning field of serotonin receptor pharmacology and integrates this
      information into a coherent perspective on the importance of serotonergic agents
      for clinical psychiatry.

PMID- 7804392
TI  - Update on dopamine receptors.
AB  - This paper reviews recent developments in dopamine receptor biology, with an
      emphasis on our recent understanding of the anatomical locations of where various
      genes for the dopamine receptors are expressed. At least five genes encoding
      dopamine receptors have been discovered. These five receptors have distinct
      pharmacological profiles as well as unique neuroanatomical distributions. While
      D1 and D2 receptors are widely expressed in many neural systems, the novel D3 and
      D4 receptors appear to be concentrated within parts of the limbic system, and the
      D5 receptor has a limited and unusual distribution. The distinct distributions of
      each of the dopamine receptors in brain facilitates a new understanding of
      potential neurochemical and neuroanatomical substrates of psychiatric illnesses
      such as schizophrenia, permits an understanding of observed actions and side
      effects of psychotropic agents, and provides clues for the rational development
      of new drugs with effects in the dopaminergic system.

PMID- 7804393
TI  - Acetazolamide in bipolar affective disorders.
AB  - Acetazolamide is a carbonic anhydrase inhibitor used for a variety of purposes,
      including adjunctively in the management of various types of epilepsy. A previous
      study on its psychotropic effects suggested the possibility of efficacy in
      atypical psychotic states, especially those characterized by cyclicity. In the
      present investigation, 16 patients with refractory affective symptomatology were
      treated with acetazolamide in a prospective open trial after exhaustive trials
      with antidepressants, lithium, carbamazepine, divalproex, and other
      anticonvulsants. Seven of the 16 (44%) responded positively, in some cases
      dramatically, for as long as 2 years. Analysis revealed that all of the
      responders were either in a depressive phase or in a rapid-cycling phase of a
      bipolar illness and that all had experienced partial positive response to at
      least one other anticonvulsant and were being maintained on anti-convulsant
      therapy when the response occurred. Salient theoretical issues are explored.

PMID- 7804394
TI  - Dissociation of "conscious desire" (craving) from and relapse in alcohol and
      cocaine dependence.
AB  - Treatment of withdrawal and postabstinence craving has yielded mixed results in
      eliminating drug and alcohol use, improving outcomes, and reducing relapse in
      those patients addicted to alcohol and drugs. To assess the role of "conscious
      desire" (or craving) for drugs/alcohol during abstinence and withdrawal in
      continued addictive drug and alcohol use, we analyzed data from 1626 patients
      voluntarily admitted to a primary rehabilitation center in Minnesota. Eighty-one
      percent and 71% of all patients completed surveys at 6 and 12 months following
      discharge. Forty-two percent were diagnosed as alcohol dependent (AD) alone, 28%
      as alcohol and drug dependent (ADD) other than cocaine, and 25% as cocaine
      dependent (CD). At 6 months following discharge, the CD group had the lowest
      abstinence rate for drugs, at 83%, compared to the AD group, at 99%, and for
      alcohol, at 76%, compared to the AD group, at 75%. The AD group had the best
      outcomes and the least slippage from 6 to 12 months for drugs and alcohol. In all
      groups craving was not a major self-reported cause of relapse. For the CD
      subgroup, impulsive action with no known cause was the most common reason for
      relapse, while the AD group cited depression. These data agree with other reports
      in the literature suggesting that relapse is not commonly related to conscious
      craving. Our experience suggests that craving is rarely the first reason given
      for relapse. Drug seeking and use are such highly ritualized, automatic behaviors
      that the addict may appear not to require the intervention of conscious thoughts
      or distinct craving states to use.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7804396
TI  - Transcriptional activity and ultrastructure of morphologically different types of
      nucleoli isolated from hepatocytes of normal and hepatectomized rats.
AB  - Morphologically different types of nucleoli were isolated from liver of normal
      and partially hepatectomized rats, to allow their ultrastructure and
      transcriptional activity to be precisely correlated. Transcriptional activity was
      estimated from the intensity of incorporation of [14C]-UTP during periods of
      maximal RNA-polymerase I activity. RNA synthesis in hepatocyte nucleoli was
      maximal at 6 and 22 h after partial hepatectomy. The changes in transcriptional
      activity coincided with changes in nucleolar ultrastructure. Pseudonucleolonemal
      nucleoli, in which the prominent nucleolonemal network has a large dense
      fibrillar component and a small granular part, were first seen 6 h after the
      operation and showed the highest transcriptional activity. After 22 h, a second
      peak of RNA synthesis was recorded. Nucleolar size had almost doubled, and most
      hepatocytes showed hypertrophy of the granular component, indicative of
      intensified pre-rRNA processing.

PMID- 7804395
TI  - Insulin-like growth factor-I receptor in the cell biology of the ameloblast: an
      immunohistochemical study on the rat incisor.
AB  - The distribution of IGF-I receptor is reported in the odontogenic epithelium and
      mesenchyme of the continuously erupting mandibular incisor of the rat by
      immunohistochemistry using a polyclonal antibody specific to the IGF-I receptor.
      Odontogenic epithelium is a unique odontogenic sequence in that all stages of the
      complex life cycle of the ameloblast are represented along the length of the
      enamel-forming aspect of the tooth. Pre-ameloblasts become post-mitotic before
      secreting enamel matrix. When the full thickness of the enamel has been formed, a
      remarkable transition in phenotype takes place in the ameloblast. It changes from
      a protein secretory cell to one active in maturation of enamel matrix by removal
      of water and protein from the increasingly mineralized matrix. The distribution
      and intensity of IGF-I receptor expression varied with the phenotypic stages of
      the ameloblasts. Diffuse cellular staining for IGF-I receptor was found during
      the active secretory phase of amelogenesis. However, towards the end of this
      phase, the staining was confirmed to granular or vesicular structures within the
      cytoplasm. These granular deposits gradually decreased as the ameloblasts made
      the transition towards enamel maturation. This transition is accompanied by
      programmed cell death (apoptosis) of approximately 25% of the ameloblasts and
      cells in this zone did not stain for IGF-I receptor. With the onset of enamel
      maturation, diffuse staining of the ameloblast layer was re-established gradually
      and staining remained evident right up to the reduced enamel epithelium, which
      joins with the oral epithelium. Strong IGF-I receptor immunoreactivity was
      observed in the stratum basale and stratum spinosum of the adjacent labial
      gingival epithelium.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7804397
TI  - Maturation of renal collecting duct cells in vivo and under perifusion culture.
AB  - The embryonic collecting duct epithelium of neonatal kidney undergoes profound
      functional changes during maturation. In its initial state as inductor epithelium
      it appears homogeneous, but differentiates into a heterogeneously composed
      collecting duct epithelium consisting of principal and intercalated cells. The
      mechanism of this terminal differentiation process is unknown. We used
      morphological and immunohistochemical methods to investigate the maturation of
      the collecting duct system in neonatal rabbit kidney and under organotypic
      culture conditions. The new perifusion culturing method allowed us to follow the
      differentiation of the ampullary collecting duct epithelium under conditions as
      close as possible to the situation within the organ. With this technique we were
      able to induce a differentiation process similar to that in the in situ
      situation. This process led to the appearance of a mixed cell population
      consisting of principal and intercalated-like cells, respectively. A continuous
      perifusion of the medium made it possible to stabilize the microenvironment under
      culture conditions and thus to maintain the heterogeneous composed collecting
      duct epithelium in a differentiated status over long periods of time.

PMID- 7804398
TI  - President's message: it is 1998: do you know who your customer is?

PMID- 7804399
TI  - Chemotherapeutic treatment of colorectal cancer: rationale, trends, and nursing
      care.
AB  - Colorectal cancer is the second leading cause of cancer-related death in America.
      Historically, chemotherapeutic treatment of colorectal cancer has met with mixed
      success. Continued research is securing a role for chemotherapy in the treatment
      of colorectal cancer, with fluoropyrimidines (5-fluorouracil and
      fluorodeoxyuridine), alone or in combination with modulating agents, being the
      most promising area of treatment. Knowledge of cell kinetics forms the basis for
      understanding chemotherapeutic activity and the management of drug-induced side
      effects. Nursing care is essential to the management of such common side effects
      as myelosuppression, stomatitis, nausea and vomiting, diarrhea, and cutaneous
      problems. Inadequate management of side effects can result in serious and
      distressing complications, including inability to complete therapy, risking an
      opportunity for potential cure or causing needless suffering and expense. In
      addition to supporting continued medical research, nurses need to pursue research
      that identifies the most effective nursing interventions for management of side
      effects from chemotherapy.

PMID- 7804401
TI  - A research primer.
AB  - Research is critical for the continued development of ET nursing knowledge.
      Although ET nurses have an interest in research, some may lack understanding of
      basic terms used in quantitative research. This article is a research primer that
      focuses on basic information about the research process. Information is presented
      about a study's purpose, literature review, conceptual framework, questions or
      hypotheses, instruments, design, sample, and statistics. The reader participates
      in the process by answering questions placed throughout the article.

PMID- 7804400
TI  - Dermal ulcer cultures: frequency and associated symptoms.
AB  - The identification of the colonized versus the infected dermal ulcer continues to
      be a major challenge for clinical practitioners. The purposes of this 3-month,
      prospective study were (1) to examine the current practice of culturing and use
      of antibiotics in treating dermal ulcers and (2) to examine associated symptoms
      of infected dermal ulcers in a 250-bed community hospital. A consecutive series
      design was used to obtain all patients (N = 63). The study revealed that 70% (44)
      of the patients dermal ulcers were not cultured. Additionally, symptoms normally
      associated with dermal ulcer infection, such as erythema, swelling, and abnormal
      drainage, were not always present in patients with infectious dermal ulcers.

PMID- 7804402
TI  - Innovative pouch modification for high-output ostomy drainage.
AB  - Numerous options are available for pouching fecal stomas when liquid output is
      relatively low. When output is high and stool has a mixed consistency, however,
      pouch selection is more limited. This article describes a method of utilizing a
      sputum specimen trap to modify a one-piece pouch to accommodate intermittently
      greater output. A successful experience with one patient is described,
      demonstrating how this pouch modification aided in a complex terminal care
      situation. Other alternatives in management of the high-output ostomy are also
      discussed.

PMID- 7804403
TI  - Pressure ulcers in extended care facilities: report of a survey.
AB  - A survey including 15 extended care facilities with access to ET nurse consulting
      services was conducted to assess current wound care protocols, practices, and
      educational backgrounds as well as requirements. Sixty-seven percent of
      facilities surveyed used a system to describe pressure ulcers. Wound care was
      provided by licensed practical nurses in 90% of the institutions and product
      decisions were made by the physician in 65% of facilities surveyed. Gauze-type
      dressings were used most frequently on all stages and types of pressure ulcers. A
      significant correlation between ulcer type and dressings used was found for stage
      II pressure ulcers only. Hydrocolloid and polyurethane film dressings were more
      likely to be used on stage II ulcers without exudate than on any other type of
      ulcer (p < 0.001). The ET nurse and a variety of other professionals, including
      product manufacturer representatives, were consulted to assess complicated
      wounds. In 9 of 15 instances, the ET nurse was rated as the best source of
      practical wound care information. Respondents preferred wound care meetings that
      were practical, included all levels of health care providers, focused equally on
      treatment and prevention, and were not expensive to attend.

PMID- 7804404
TI  - President message: opportunities emerging from health care reform.

PMID- 7804405
TI  - Assessment, diagnosis, and treatment of constipation in childhood.
AB  - The evaluation of chronic constipation with or without fecal soiling in children
      must begin with a careful history and physical examination. Constipation and
      fecal soiling is caused in fewer than 10% of patients by anatomic, neurologic,
      endocrine, or metabolic conditions. No specific organic cause can be found in
      more than 90% of affected children, but anorectal functions--such as rectal
      sensation, rectal contractility, and relaxation of the external anal sphincter
      and pelvic floor muscles during straining for defecation--are impaired. Most
      patients will benefit from a program designed to clear fecal impaction with
      enemas, prevent fecal impaction with enemas, prevent fecal impaction with
      laxatives, and promote regular bowel habits with scheduled toilet sittings.

PMID- 7804406
TI  - A historical perspective of stomal construction.
AB  - Building on past accomplishments in the field of enterostomal therapy has
      resulted in the high quality of care available today for patients with stomas.
      Rupert B. Turnbull, Jr., MD, FACS, is the acknowledged "Father of Enterostomal
      Therapy" because of his pioneer surgical contributions and because of his call to
      Norma Gill, ET, to lead the technical development under his guidance. This 1993
      Turnbull Memorial Lecture deals with historical interactions and developments, as
      seen by Dr. Turnbull's partner since the early years of the specialty's
      development.

PMID- 7804407
TI  - Excess granulation tissue around a gastrostomy tube exit site with peritubular
      skin irritation.

PMID- 7804408
TI  - The synergy of pathways and algorithms: two tools work better than one.
AB  - BACKGROUND: Clinical quality improvement efforts at the Medical Center Hospital
      of Vermont (MCHV) led to the development of critical pathways, which show the
      ideal plan of care, and algorithms, which help clinicians make one of many
      complicated decisions within a plan of care. A synergy appears to develop when
      pathways and algorithms are used together. DEVELOPMENT OF PATHWAYS AND
      ALGORITHMS: A steering committee supports and oversees pathway and algorithm
      efforts. A quarterly tracking report updating progress for all pathways and
      algorithms is circulated to all nurse managers, medical staff, and
      administrators. When combining pathways and algorithms, the pathway is created
      first. Algorithms are developed for trouble spots within a pathway. CORONARY
      ARTERY BYPASS GRAFT (CABG) PATIENTS: Having developed the pathway for CABG
      patients, the CABG case management team meets monthly to review outcomes and
      variances. For example, an algorithm for managing atrial arrhythmias--the chief
      cause of variance for one month's results--was developed. The combination of
      pathways and algorithms for CABG patients has resulted in a reduction of 2.5 days
      for total length of stay (including 1 day on the surgical intensive care unit
      [SICU]), for a mean cost savings of $3,500. Re-admission to the SICU,
      reintubation, and mortality rates have all decreased. CONCLUSION: The idea of
      reaping the benefits of both pathways and algorithms is becoming more popular at
      MCHV, where teams use algorithms to improve on complicated processes underlying
      the pathways.

PMID- 7804409
TI  - A survey-based benchmarking approach for health care using the Baldrige quality
      criteria.
AB  - BACKGROUND: Since 1988, manufacturing and service industries have been using the
      Malcolm Baldrige National Quality Award to assess their management processes (for
      example, leadership, information, and analysis) against critical performance
      criteria. Recognizing that the typical Baldrige assessment is time intensive and
      dependent on intensive training, The Pacer Group, a consulting firm in Dayton,
      Ohio, developed a self-assessment tool based on the Baldrige criteria which
      provides a snapshot assessment of an organization's management practices. STUDY:
      The survey was administered at 25 hospitals within a health care system.
      Hospitals were able to compare their scores with other hospitals in the system,
      as well as the scores of a Baldrige award winner. Results were also analyzed on a
      systemwide basis to identify strengths and weaknesses across the system. RESULTS:
      For all 25 hospitals, the following areas were identified as strengths:
      management of process quality, leadership, and customer focus and satisfaction.
      Weaknesses included lack of employee involvement in the quality planning process,
      poor design of quality systems, and lack of cross-departmental cooperation.
      EXAMPLE: One of the surveyed hospitals launched improvement initiatives in
      knowledge of improvement tools and methods and in a patient satisfaction focus. A
      team was formed to improve the human resource management system. Also, a new unit
      was designed using patient-centered care principles. A team re-evaluated every
      operation that affected patients on the unit. CONCLUSION: A survey modeled after
      the Baldrige Award criteria can be useful in benchmarking an organization's
      quality improvement practices.

PMID- 7804410
TI  - Using mortality rates as a screening tool: the experience of the Department of
      Veterans Affairs.
AB  - BACKGROUND: Despite widespread agreement that outcome analyses should be followed
      by in-depth review of the care provided by outlier providers, there are few, if
      any, reports in the literature describing the effectiveness of this approach to
      quality improvement. In 1991, the Department of Veterans Affairs (VA) completed a
      study to measure hospital-specific mortality rates for VA facilities and to use
      these rates as a screening tool for focused medical record reviews. METHODS: The
      first phase of the project consisted of a comparison of fiscal year 1986
      mortality rates for each VA medical center with aggregated VA data, using
      logistic regression analysis to adjust for patient characteristics related to
      mortality. In the second phase, medical record reviews of cases from hospitals
      with elevated levels of mortality were conducted. RESULTS: The mortality rate
      analysis identified 44 facilities with rates that were significantly elevated
      overall or within specific patient categories. Both the mortality rate analysis
      and the medical record review suggested that quality concerns were more common in
      predominantly psychiatric medical centers than in other facilities. CONCLUSION:
      The study uncovered important opportunities for improvement, particularly
      regarding the quality of medical care provided in VA psychiatric hospitals,
      suggesting there is value in performing intensive review of outlier providers in
      outcome analyses. However, serious questions remain concerning the validity of
      the use of administrative data-bases to assess hospitalwide mortality.

PMID- 7804411
TI  - Review criteria aren't what they used to be--making the transition from QA to QI:
      an interview with Richard E. Burney, MD. Interview by Louise Kaegi.

PMID- 7804412
TI  - Acute arthritis.

PMID- 7804413
TI  - Osteomyelitis.

PMID- 7804414
TI  - Total hip arthroplasty.

PMID- 7804415
TI  - Cuban epidemic optic neuropathy. Mitochondrial DNA analysis.
AB  - OBJECTIVE: To search for mitochondrial DNA (mtDNA) mutations previously
      associated with Leber's hereditary optic neuropathy (LHON) in patients with an
      optic neuropathy that appeared in epidemic form in Cuba. METHODS: Twelve Cuban
      patients underwent a comprehensive neuro-ophthalmologic examination and were
      found to have a characteristic optic neuropathy, Cuban epidemic optic neuropathy
      (CEON). At the same time, one patient was diagnosed with typical LHON that
      occurred during the epidemic. Blood samples were taken from these patients as
      well as from 3 controls with normal neuro-ophthalmologic examinations. These
      samples were blindly analyzed for 9 LHON-associated mtDNA mutations by molecular
      genetic methods. RESULTS: CEON bore clinical and epidemiological similarity to
      LHON, however, family histories, systemic symptoms (especially weight loss and
      polyuria), and symptoms of peripheral neuropathy permitted a clinical
      distinction. None of the 12 patients with CEON or 3 controls had any of the LHON
      associated mtDNA mutations. Only the patient with clinical LHON, who did not meet
      the case definition for CEON, harbored the 11778 mtDNA mutation. CONCLUSIONS:
      Known mtDNA mutations are not found frequently in CEON patients but they may
      contribute to some cases of Cuban optic neuropathy. CEON may represent an
      acquired variety of mitochondrial dysfunction induced by nutritional
      deficiencies, toxins, or both. Alternatively, CEON patients may also harbor as
      yet undiscovered mtDNA mutations that contribute to their genetic susceptibility.

PMID- 7804416
TI  - Mitochondrial DNA mutations in Cuban optic and peripheral neuropathy.
AB  - OBJECTIVE: To investigate the potential role of mitochondrial DNA (mtDNA)
      mutations in the recent outbreak in Cuba of optic neuropathy and peripheral
      neuropathy (COPN). DESIGN AND METHODS: Historical features were reviewed and
      neuro-ophthalmologic examinations were performed on a sample of COPN patients (n
      = 9) and Cuban patients with other forms of optic neuropathy (n = 2). Molecular
      genetic methods were then used to test for the presence of 9 mtDNA mutations that
      were previously associated with Leber's hereditary optic neuropathy (LHON).
      RESULTS: Two (22%) of 9 COPN patients harbored an LHON-associated mtDNA mutation
      at nucleotide position 9438 and a novel mutation at nucleotide position 9738 in
      the cytochrome c oxidase subunit III gene. None of the Cuban patients harbored
      any of the 8 other LHON-associated mtDNA mutations. Detailed sequence analysis
      revealed that the Cuban patients could be divided into 7 distinct mtDNA
      haplotypes and that the 2 COPN patients with mtDNA mutations in the cytochrome c
      oxidase subunit III gene were not members of the same maternal lineage.
      CONCLUSIONS: The pathogenesis of epidemic COPN is likely complex and
      multifactorial. Our preliminary results in a small sample of Cuban patients
      suggest that mtDNA mutations may play a role in some cases. mtDNA mutations may
      render an individual genetically susceptible to a variety of factors that impair
      oxidative phosphorylation, including nutritional deficiency, tobacco, alcohol,
      and other toxins.

PMID- 7804417
TI  - Annual review in neuro-ophthalmology. The anterior visual pathways.

PMID- 7804418
TI  - Silicone and blindness: computed tomography imaging.

PMID- 7804419
TI  - Large optic nerve with central retinal artery and vein occlusions from optic
      neuritis/perineuritis rather than tumor.

PMID- 7804420
TI  - Involuntary ocular deviations and generalized dystonia in multiple sclerosis. A
      case report.
AB  - A man with chronic relapsing multiple sclerosis developed involuntary ocular
      deviations, blepharospasm, torticollis, and chorea of the right arm and head
      during relapses precipitated by urinary tract infections. An MR scan showed
      lesions adjacent to the right caudate and lentiform nuclei.

PMID- 7804422
TI  - Anterior ischemic optic neuropathy in Graves' disease.
AB  - Optic neuropathy occurred in two patients suffering from Graves' disease with
      marked limitation of eye movement. Optic nerve changes were moderate. They
      consisted of parapapillary flame-shaped hemorrhages, swelling of the disc, and
      bundle defects in the visual field on the involved side. This clinical pattern
      suggested that the optic neuropathy was anterior and ischemic in nature. In one
      patient, symptoms of optic neuropathy were noted 3 days after starting stretching
      exercises with the ocular muscles, performed following a friend's advice in an
      attempt to prevent increase in restrictive myopathy. In patients with Graves'
      disease, it is conceivable that mild optic neuropathy occasionally occurs as a
      result of elevation in intraocular pressure, and stretching exercises of the
      ocular muscles might consequently favor such ischemic events. In the mechanisms
      of optic nerve involvement associated with Graves' disease, the role of ischemia
      should be considered in addition to the widely accepted role of optic nerve
      compression by enlarged extraocular muscles, at the level of the orbital apex.

PMID- 7804421
TI  - Folate-responsive optic neuropathy.
AB  - We examined six patients who presented with bilateral, progressive visual loss.
      Each patient had a bilateral decrease in visual acuity, poor color vision, and
      central or cecocentral scotomas. Optic nerve head appearance varied from normal
      to diffusely pale. All patients consumed tobacco, ethanol, or both. Each patient
      was folate deficient and had normal vitamin B12 levels. Patients were treated
      with oral folic acid, 1 mg per day. Visual acuity improved bilaterally in all
      patients (mean: five lines in 2 months). Folate deficiency should be considered
      in any patient with progressive bilateral optic neuropathy of unknown etiology.
      Treatment with folic acid can result in significant improvement in visual
      function.

PMID- 7804423
TI  - A diagnostic quartet in leptomeningeal infiltration of the optic nerve sheath.
AB  - A rare case of optic leptomeningeal carcinomatosis secondary to a rectal
      adenocarcinoma is recorded. The presentation of rectal disease with blindness is
      unique. A diagnostic quartet of symptoms and signs of leptomeningeal infiltration
      of the optic nerve sheath is proposed and its value emphasized by the inability
      of further investigation to confirm the clinical diagnosis. The investigation and
      treatment of leptomeningeal carcinomatosis is reviewed.

PMID- 7804424
TI  - Fourth ventricular hemangioblastoma associated with pheochromocytoma and renal
      medullary fibroma.
AB  - Intraventricular hemangioblastomas are exceptionally rare. Of the cases described
      in the literature, very few were associated with von Hippel-Lindau disease. We
      present a highly unusual case of a fourth ventricular hemangioblastoma associated
      with a pheochromocytoma and a renal medullary fibroma. This may represent a forme
      fruste of the von Hippel-Lindau complex. A workup for papilledema resulted in the
      discovery of this rare finding.

PMID- 7804425
TI  - Slavin's Prism Dissociation test.

PMID- 7804426
TI  - Superior oblique myokymia.

PMID- 7804427
TI  - Captopril reduces collagen and mast cell and eosinophil accumulation in pig serum
      induced rat liver fibrosis.
AB  - The effect of captopril on the development of hepatic septal fibrosis in a
      specific experimental model produced by repeated injections of whole pig serum
      into the peritoneal cavity of rats was studied. The results afforded four basic
      conclusions. First, the experimental model used seems to be a pure form of septal
      fibrosis, which depends on active tissue fibroplasia, without hepatocyte
      necrosis. The fibrotic septa, located between limiting plates of adjacent classic
      hepatic lobules, and delimiting the classic liver lobule, consisted of collagen
      fibers infiltrated by eosinophils, mast cells, fat-storing cells (Ito cells),
      transitional cells and interstitial fibroblasts. Second, the angiotensin
      converting enzyme inhibitor captopril attenuated the hepatic fibrosis induced by
      pig serum administration, as proven by a decrease in hepatic hydroxyproline
      concentration and histological examination of the liver. Third, this attenuation
      of hepatic fibrosis might be related, at least in part, to diminished mast cell
      and eosinophil accumulation in the hepatic tissue. Finally, these data may
      indicate a novel action of angiotensin-converting enzyme inhibitor in general,
      and for captopril in particular, as drugs potentially capable of reducing
      eosinophils in fibrotic processes.

PMID- 7804428
TI  - Quantitative morphology of human cirrhotic livers. Part I: Parameter expression
      of pattern as a basis for computerized classification.
AB  - Although classification is a long-used method of histopathology, a reproducible
      one has yet to be created. We established a most adequate classification of
      cirrhosis from a geometric and statistical point of view, by reducing its form to
      a set of quantities and submitting the data to multivariate analysis. In this
      article, methods for quantification are described as a preliminary step for the
      statistical treatment that appears in another paper. The pattern was reduced to a
      set of four quantities: (i) the mean nodular radius; (ii) the coarseness; (iii)
      the mean septal thickness; and (iv) the degree of nodular separation. A model of
      dispersed spheres with various radii r was employed to assimilate cirrhosis; r
      was assumed to follow a logarithmic normal distribution. The parameters of this
      distribution were estimated stereologically from measurements on microscopic
      sections of chord lengths lambda generated from nodules by a test line. The
      coarseness was defined as the volume % of nodules larger than 1.5 mm in r. The
      mean septal thickness was determined stereologically on a plate model, into which
      the actual septa were transformed without changing their volume or surface
      density. The degree of nodular separation p theta was defined as a two
      dimensional parameter, based on the curvature of nodulo-septal borders. It was
      demonstrated in several examples how accurately a set of these quantities
      describes various patterns of cirrhosis.

PMID- 7804429
TI  - Quantitative morphology of human cirrhotic livers. Part II: The statistically
      adequate morphological classification of liver cirrhosis. Multivariate analysis
      from quantified data of form.
AB  - In a previous report, we developed methods by which to quantify various patterns
      of cirrhosis. A set of parameters were used: (i) the mean nodular radius; (ii)
      the coarseness; (iii) the mean septal thickness; and (iv) the degree of nodular
      separation. This was applied to 70 cirrhotic livers in an attempt to establish a
      reproducible classification, and the data were subjected to four-dimensional
      cluster analysis (Ward method) using a mainframe computer. Five clusters
      appeared: cluster A, fine nodules, thin septa; cluster B, coarse nodules,
      relatively thin septa; cluster C, fine nodules, thick septa; cluster D, extremely
      coarse nodules; and cluster E, coarse nodules, thin septa and incomplete
      nodulation. Of these, cluster A was considered to correspond to the nutritional
      type of Gall, cluster B to posthepatitic type (Nagayo's Type B), cluster C to
      postnecrotic type (Nagayo's Type A) and cluster E to the subtype of posthepatitic
      cirrhosis with incomplete nodulation (Miyake's Type BI). Cluster D comprised
      cases with extremely coarsened nodules. The reproducibility of this clustering
      was fully ensured by linear discriminant analysis. Another discriminant analysis,
      the canonical, allowed us to visualize the separation of clusters in a two
      dimensional (2-D) scatter diagram. We thus managed to establish a most adequate
      classification from a geometric and statistical point of view.

PMID- 7804430
TI  - Overexpression of p53 protein and Ki67 proliferative index in hepatocellular
      carcinoma: an immunohistochemical study on 109 Italian patients.
AB  - The overexpression of p53 protein and the Ki67 proliferative index was evaluated
      in 96 hepatocellular carcinomas (HCC), 67 in cirrhotic livers and 29 in non
      cirrhotic ones, and in 13 non-carcinomatous lesions, all surgically resected from
      Italian patients. Overexpression of p53 was detected only in carcinomatous
      lesions, and was significantly related to the grade of HCC (P < 0.001). In fact,
      p53 was observed in 7/7 (100%) cases of grade IV, 13/43 (30.3%) of grade III, and
      10/46 (21.7%) of grade II. The relationship between p53 and Ki67 scores was
      determined in serial sections from corresponding areas of both diffuse and patchy
      immunoreactivity. In the overall population, p53-positive tumors showed a
      significantly higher Ki67 score (15.9 +/- 5.5% vs 9.2 +/- 4.3% [P < 0.001]). This
      observation was evident in all grades of HCC.

PMID- 7804431
TI  - Lymphokine-activated killer cytotoxicity against pancreas adenocarcinoma cell
      lines and vascular endothelial cells.
AB  - Eight pancreas carcinoma cell lines of duct cell origin (PCI-6, 10, 19, 24, 35,
      43, 55, and 64) were established. Using one of these lines, PCI-24, human
      umbilical vein endothelial cells (HUVEC), and several recombinant cytokines,
      conditions and specificity of anti-PCI LAK induction were investigated, with the
      focus on a search for lymphokine-activated killer (LAK) activity that
      differentiates neoplastic (PCI) from non-neoplastic (HUVEC) cells. Interferon
      gamma (IFN-gamma), IFN-alpha, IL-4, IL-6, and IL-7, but not tumor necrosis factor
      alpha (TNF-alpha) or IL-1 beta, induced a weak LAK activity against PCI-24,
      whereas IL-2-induced (1000 U/mL) LAK exhibited a far more potent cytotoxicity.
      When these cytokines were added at the suboptimal dose IL-2 (100 U/mL), no
      significant augmentation in LAK activity was induced. Staphylococcal protein A
      (SpA) induced LAK activity as potent as that seen with IL-2 (1000 U/mL). Both IL
      2-induced and SpA-induced LAK had a potent, dose-dependent cytotoxicity against
      HUVEC. HUVEC inhibited both IL-2- and SpA-induced LAK cytotoxicity against PCI-24
      to almost the same extent as seen with PCI-24. Thus, two potent LAK-inducers did
      not generate LAK activity that differentiates neoplastic from non-neoplastic
      cells. Thus, in vitro cytotoxicity of LAK against non-neoplastic endothelial
      cells is unavoidable when handling cytokines in LAK induction.

PMID- 7804432
TI  - Histologic and immunohistochemical study of clinically non-functioning pituitary
      adenomas: special reference to gonadotropin-positive adenomas.
AB  - Seventy-five clinically non-functioning pituitary adenomas were characterized in
      terms of their histologic and immunohistochemical features. Fourteen adenomas
      (18.7%) were positive for hormones other than gonadotropins. These included two
      somatotroph adenomas, three lactotroph adenomas, four thyrotroph adenomas, four
      corticotroph adenomas and one unusual plurihormonal adenoma. Fifty-five adenomas
      (73.3%) were exclusively positive for one or more gonadotropin subunits (beta
      follicle stimulating hormone, beta-luteinizing hormone, and alpha-subunit of
      glycoprotein hormones), but negative for other hormones such as growth hormone
      and beta-thyrotropin. Histologically, a papillary arrangement along the capillary
      was most characteristically observed in the gonadotropin-positive adenomas. Five
      of six adenomas negative for any pituitary hormones exhibited the typical
      papillary structure. Thus, approximately 80% of clinically non-functioning
      adenomas constituted a single tumor group that shared the common histologic
      features of gonadotroph adenomas. These findings suggest that nearly all tumor
      types of clinically non-functioning adenomas can be diagnosed solely by light
      microscopy in combination with immunohistochemistry, and that the vast majority
      of them may be gonadotroph adenomas.

PMID- 7804433
TI  - A case of pseudolymphoma of the liver.
AB  - A case of pseudolymphoma (reactive lymphoid hyperplasia) of the liver in a 66
      year old female is presented. A tumor-like lesion was incidentally discovered in
      the liver during clinical follow up of diabetes mellitus. The hepatic lesion was
      resected because malignant lymphoma was suspected after a needle biopsy. Grossly,
      the lesion was well-defined and measured 1.0 x 1.5 x 1.0 cm. Microscopically, the
      lesion consisted of hyperplastic lymphoid follicles with distinctive germinal
      centers and interfollicular areas consisting of mature lymphocytes and plasma
      cells. An immunohistological study revealed that the lymphoid cells of the lesion
      were polyclonal in immunophenotypes. These histological and immunohistochemical
      findings strongly suggested a pseudolymphoma and not hepatic inflammatory
      pseudotumor. This case was diagnosed as pseudolymphoma of liver. Only a few cases
      of hepatic pseudolymphoma have so far been reported in the English literature.

PMID- 7804434
TI  - Malignant lymphoma of the esophagus associated with macroglobulinemia: report of
      a case.
AB  - A case of non-Hodgkin's lymphoma of the esophagus in a 74 year old man is
      presented. Grossly, the surgically removed esophagus had a fusiform submucosal
      mass covered with smooth surfaced mucosa. Microscopic examination revealed that
      the mass consisted of a dense infiltrate of small to medium-sized lymphoid cells
      with plasmacytoid differentiation, leading to a diagnosis of diffuse small cell
      lymphoma with lymphoplasmacytic subtype. Laboratory data as well as
      immunohistochemical studies proved that the lymphoma produced monoclonal
      immunoglobulin M, giving rise to macroglobulinemia.

PMID- 7804435
TI  - Intraductal carcinoma of the breast arising in sclerosing adenosis.
AB  - An unusual case of intraductal carcinoma of the breast arising in sclerosing
      adenosis is reported. A 49 year old Japanese woman noticed a lump in her right
      breast 3 years before she sought medical advice. Histologic examination of the
      lumpectomy specimen showed, adjacent to intraductal papilloma, sclerosing
      adenosis involved in a neoplastic cellular proliferation with cribriform pattern
      and comedo necrosis. Immunohistochemical study with anti-actin antibodies
      discriminated intraductal carcinoma from adjacent sclerosing adenosis by
      highlighting myoepithelial components in the latter. Extensive sampling revealed
      no carcinoma outside the sclerosing adenosis, implying that the intraductal
      carcinoma did originate in the tubules of sclerosing adenosis. A review of the
      literature indicated that the ductal to lobular ratio among carcinoma in situ
      concurring with sclerosing adenosis is about 1:2. The average age of patients
      with ductal and lobular carcinoma in situ in sclerosing adenosis is 39 and 43.7,
      respectively. It is suggested that carcinoma in situ arising in sclerosing
      adenosis and fibroadenoma have a similar biological basis.

PMID- 7804437
TI  - G-proteins: implications for pathophysiology and disease.
AB  - This article focuses on the involvement of G-proteins in neuroendocrine
      secretion, cell growth and phenotype alterations. The current concept of hormonal
      activation of the GTPase cycle, as well as the molecular diversity of G-proteins
      families and receptor*G-protein*effector coupling, are described. Also described
      are certain G-proteins as possible proto-oncogenes and how point mutations and
      frame shift mutations alter G-protein function and determine the characteristics
      of various endocrine diseases. The article outlines in detail how receptors and G
      proteins interact in prolactin and growth-hormone-secreting pituicytes, how G
      proteins are involved in the growth and differentiation of preadipocytes and
      osteoblasts. All in all, it seems that hormonal activation through G-proteins is
      modulated through direct intra- and inter-signalling system cross-talk at the
      plasma membrane level (short-term) and through interactions on the level of
      transcription (HREs) from tyrosine kinases, steroid-like hormones and metabolic
      pathways. Pharmacological intervention to treat diseases where G-proteins are
      involved should take both long and short-term regulatory phenomena into
      consideration.

PMID- 7804436
TI  - Ossifying subcutaneous tumor with myofibroblastic differentiation: a variant of
      ossifying fibromyxoid tumor of soft parts?
AB  - Immunohistochemical, ultrastructural, and flow cytometric studies were performed
      on an ossifying soft-tissue tumor, presumed to be a variant of ossifying
      fibromyxoid tumor of soft parts, which was located in the subcutis of the left
      buttock of a 76 year old Japanese woman. Histologically, this was a benign
      looking spindle, oval, or round cell lesion, having a fibrous capsule with a
      discontinuous rim of bone as seen in typical cases. However, this lesion was also
      characterized by a high degree of cellular proliferation in storiform and whorl
      arrangements, extensive ossification, osteoid and metaplastic bone formation and
      absence of myxoid features. In an immunohistochemical study using formalin-fixed,
      paraffin-embedded sections, many tumor cells expressed vimentin, S-100 protein,
      Leu-7, neuron specific enolase, and desmin. Ultrastructurally, this neoplasm
      consisted of fibroblast-like cells and myofibroblast-like cells. This tumor had
      an aneuploid DNA content. No recurrence has been observed for 16 months. These
      results suggest that the neoplastic cells may show the phenotypic expressions of
      myofibroblast and also osteogenic differentiation.

PMID- 7804438
TI  - Clinical relevance of somatostatin receptor imaging.

PMID- 7804439
TI  - [111In-DTPA-D-Phe1]octreotide scintigraphy in patients with carcinoid tumours:
      the predictive value for somatostatin analogue treatment.
AB  - This study was performed to evaluate whether the presence or absence of
      somatostatin receptors in malignant carcinoid tumours detected by [111In-DTPA-D
      Phe1]octreotide scintigraphy can be used to predict response to somatostatin
      analogue treatment. Thirty patients were investigated, 28 with midgut carcinoid
      tumours and two with foregut carcinoid tumours. Twenty-seven patients showed
      pathological uptake in tumour lesions at scintigraphy; of these, 22 responded to
      somatostatin analogue treatment using octreotide, somatuline or octastatin, while
      five patients failed to respond. None of the three patients displaying negative
      scintigraphic investigations responded to treatment with somatostatin analogues.
      These results show a good correlation between the somatostatin receptor status
      and the patients' ability to respond to somatostatin analogue treatment (p =
      0.014). We conclude that somatostatin receptor scintigraphy using [111In-DTPA-D
      Phe1]octreotide can be used to select patients with malignant carcinoid tumours
      suitable for somatostatin analogue treatment and exclude those that will not
      benefit from such medication.

PMID- 7804441
TI  - Effect of liver damage on the pharmacokinetics of dexamethasone.
AB  - By measuring the pharmacokinetics of dexamethasone in 48 patients with various
      degrees of disturbances in liver function, we could demonstrate a decrease in the
      metabolic clearance of this steroid by 53% if the activity of the plasma
      cholinesterase was lowered to less than 2 kU/l. Results suggest that the dosage
      of dexamethasone given for diagnostic or therapeutic purpose needs to be adjusted
      in such patients.

PMID- 7804440
TI  - Exaggerated blood pressure response to angiotensin II in patients with Cushing's
      syndrome due to adrenocortical adenoma.
AB  - We studied the roles played by the renin-angiotensin system in inducing
      hypertension in nine patients with Cushing's syndrome (CS) resulting from
      adrenocortical adenoma, and compared them with those in patients with primary
      aldosteronism (PA), renovascular hypertension (RVH) and essential hypertension
      (EH). In the CS group, each parameter, including serum potassium, plasma renin
      activity, plasma aldosterone, deoxycorticosterone and corticosterone
      concentrations, is within the normal range. However, plasma renin activity in the
      CS group was lower than that in the RVH group but higher than that in the PA
      group, and plasma aldosterone concentration was lower than that in each RVH or PA
      group. These findings indicated that the CS group had a different type of
      hypertension from that in either RVH or PA, in which the renin angiotensin system
      or mineralocorticoids play an important role in hypertension. Meanwhile,
      captopril (50 mg) administration either with or without indomethacin pretreatment
      decreased the mean blood pressure in the CS group, although captopril failed to
      change it in the PA group or in normal subjects. Furthermore, the pressor
      response to exogenous angiotensin II in the CS group was higher than that in the
      RVH or EH group, but was not different from that in the PA group. Thus, the
      hypertension in patients with CS due to adrenocortical adenoma appears to be
      mediated through a change in the renin-angiotensin system in the form of
      exaggerated pressor responses to angiotensin II.

PMID- 7804442
TI  - Oral dexamethasone administration: new pharmacological test for the assessment of
      growth hormone secretion.
AB  - Acute intravenous (i.v.) dexamethasone administration has been described recently
      as a new test for the diagnosis of growth hormone (GH) deficiency. In the present
      study, a new protocol of dexamethasone administration was evaluated. Twelve
      normal adults and 18 normal prepubertal children were studied. The dexamethasone
      i.v. test was performed in six adults at a dose of 4 mg and 12 children at a dose
      of 2 mg/m2. Blood samples were collected 15 min before, at time zero and every 15
      or 30 min during 5 h, resulting in a total of 16 samples. In the remaining six
      adults and six children, 8 and 4 mg, respectively, of dexamethasone were
      administered orally at the subject's home, and blood sampling started 90 min
      later when they arrived at the hospital. Plasma GH was measured by
      radioimmunoassay. The dexamethasone-induced GH response (mean +/- SEM,
      micrograms/l) to the i.v. or oral protocol did not differ in either the adults
      (i.v. 8.2 +/- 2.1; oral 8.0 +/- 1.6) or the children (i.v. 14.9 +/- 1.3; oral
      13.6 +/- 1.8). It is concluded that the simpler protocol of acute oral
      dexamethasone administration hereby presented can be a safe and suitable test of
      GH secretion.

PMID- 7804443
TI  - Induction of follicle maturation and ovulation by gonadotropin administration in
      women with beta-thalassemia.
AB  - The objective of this paper was to assess the ability of gonadotropin
      administration to induce ovarian steroidogenesis, follicle maturation and
      ovulation in hypogonadal women affected by beta-thalassemia. Thirteen hypogonadal
      thalassemic women underwent a test with gonadotropin-releasing hormone (GnRH),
      with estimation of serum follicle-stimulating hormone (FSH) and luteinizing
      hormone (LH) levels. They were then administered human menopausal gonadotropin
      (hMG) for a period ranging from 11 to 15 days with a total dose variable from
      3,300 to 4,200 IU. In each patient, the initial dosage of 300 IU daily, adopted
      for the first 9 days, was modified subsequently according to the ovarian
      morphology, as shown by serial echographic examinations and by serum estradiol
      levels. In those patients in whom a dominant follicle was evidenced and the
      occurrence of pregnancy could be excluded, induction of ovulation was attempted
      by administration of 10,000 IU of human chorionic gonadotropin (hCG). All
      patients displayed a reduced LH and FSH rise in response to GnRH. Upon hMG
      administration, they exhibited echographic evidence of follicular growth with a
      clear-cut increase of serum estradiol, which peaked between the 9th and the 16th
      day from the start of treatment. In two out of three patients in whom a dominant
      follicle developed, ovulation was induced successfully by hCG injection, as shown
      by the increase of serum progesterone and by the ultrasonographic demonstration
      of a corpus luteum. This study has shown that, by proper pharmacological
      stimulation, the steroidogenic function of the gonads and even ovulation can be
      reinstated in hypogonadal thalassemic women.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7804444
TI  - Tumour necrosis factor alpha during human pregnancy and labour: maternal plasma
      and amniotic fluid concentrations and release from intrauterine tissues.
AB  - The aims of this study were: to quantify immunoreactive tumour necrosis factor
      alpha (TNF-alpha) concentrations in maternal plasma and amniotic fluid obtained
      from women during pregnancy and labour, both at term and preterm; and to
      establish the effects of bacterial endotoxin and cytokines on the in vitro
      release of TNF-alpha from intrauterine tissues. Maternal plasma TNF-alpha
      concentrations did not change during pregnancy (457.2 +/- 102.9 ng/l, mean +/-
      SEM, N = 52) or at the time of labour (543.5 +/- 138.6 ng/l, N = 43). In
      contrast, amniotic fluid TNF-alpha concentrations increased significantly (p <
      0.05) during pregnancy (early pregnancy, EP, 93.0 +/- 24.8 ng/l, N = 7; preterm
      not-in-labour, PNIL, 186.8 +/- 42.9 ng/l, N = 16; term not-in-labour. TNIL, 499.7
      +/- 150.9 ng/l, N = 13) and in association with preterm labour (preterm in
      labour, PIL, 958.7 +/- 575.6 ng/l, N = 5 vs PNIL, 186.8 +/- 42.9 ng/l, N = 16).
      Choriodecidual and placental explants (N = 3) maintained in in vitro culture
      released TNF-alpha. Furthermore, the release of TNF-alpha was increased
      significantly (p < 0.05) by bacterial endotoxin (lipopolysaccharide, 10 ng/l-10
      mg/l) but was not affected by the following cytokines at the indicated doses:
      interleukin-1 alpha (0.28 nmol/l), interleukin-6 (12.5 nmol/l), granulocyte
      colony-stimulating factor (2.5 nmol/l), granulocyte-macrophage colony-stimulating
      factor (35 nmol/l), macrophage colony-stimulating factor (1.2 nmol/l), leukaemia
      inhibitory factor (0.45 nmol/l) and transforming growth factor-beta (0.4
      nmol/l).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7804445
TI  - Expression of chorionic gonadotrophin in human pituitary adenomas.
AB  - In addition to the classical anterior pituitary hormones, many human pituitary
      adenomas express hormone genes ectopically. Expression of glycoprotein hormone
      alpha-subunit and, less commonly, free luteinizing hormone beta (LH-beta) or
      follicle-stimulating hormone beta is characteristic of endocrinologically
      inactive adenomas, a subgroup thought to be derived predominantly from the
      gonadotroph line. Thyrotrophin beta expression in these tumours is unusual, and
      specific chorionic gonadotrophin beta (CG-beta) expression, identified using
      oligonucleotide probes that reliably distinguish LH-beta and CG-beta in situ, is
      not well described. Using in situ hybridization histochemistry with a CG-beta
      transcript-specific oligonucleotide probe and a non-specific LH/CG-beta
      oligonucleotide and riboprobe, we have demonstrated specific CG-beta expression
      in two of 35 random pituitary adenomas; LH-beta expression occurred in a further
      eight adenomas. Unlike prolactin, growth hormone and proopiomelanocortin, which
      are transcribed in the vast majority of cells in their respective hormone
      positive tumour subtypes, the pattern of LH/CG-beta was typically a scattering of
      single or small clusters of hormone-positive cells in a predominantly LH/CG-beta
      negative tumour. Finally, although bona fide CG-beta expression in human
      pituitary adenomas does occur, it is only at an incidence similar to that
      described for carcinomas of other tissues.

PMID- 7804446
TI  - Sex hormone-binding globulin mRNA levels in human uterine endometrium.
AB  - Sex hormone-binding globulin (SHBG) is a specific steroid hormone-binding protein
      that plays a role in transporting dihydrotestosterone, testosterone and estradiol
      17 beta (E2), altering their concentration in blood and influencing their
      biological action. Recently it has been reported that immunoreactive SHBG is
      localized in target tissues and that SHBG mRNA was identified in human
      endometrial and prostatic cell lines. In the present work, SHBG mRNA was detected
      in human normal endometrial tissues using Northern blot analysis and polymerase
      chain reaction. Its level was higher (p < 0.02) in the secretory phase than in
      the proliferative phase. In the secretory phase, the endometrial SHBG mRNA level
      was correlated positively with serum E2 and progesterone level (p < 0.05).
      However, there was a negative correlation between endometrial SHBG mRNA level and
      serum E2/progesterone ratio (p < 0.01). These findings suggest that SHBG is
      synthesized in the uterine endometrium and a part of its synthesis is regulated
      complexly by sex steroid hormones such as E2 and progesterone.

PMID- 7804447
TI  - Analysis of proteoglycan synthesis by retro-ocular tissue fibroblasts under the
      influence of interleukin 1 beta and transforming growth factor-beta.
AB  - Retro-ocular tissue fibroblasts are supposed to be responsible for the deposition
      of glycosaminoglycan in Graves' ophthalmopathy. We have reported in a preliminary
      fashion that interleukin 1 beta (IL-1 beta) and transforming growth factor-beta
      (TGF-beta) increased the rate of [35S]sulfate incorporation into proteoglycans
      two to five times the control in culture of retro-ocular tissue fibroblasts. The
      increase in the rate of [35S]sulfate incorporation into proteoglycan will occur
      as a result of: (a) net increase of proteoglycan synthesis; (b) elongation of
      glycosaminoglycan chains; (c) increased number of glycosaminoglycan chains; (d)
      oversulfation of glycosaminoglycan chains; (e) increase in cell number; (f)
      decreased rate of degradation. We have analyzed which mechanism is important for
      the increase of [35S]sulfate into proteoglycans observed in human retro-ocular
      tissue fibroblasts under the influence of cytokines. The last two possibilities
      (e, f) were ruled out because during the observation period there was no
      consistent proliferation of the cells and no decrease in the rate of degradation
      of proteoglycan examined by pulse-chase experiment. Cytokines did not change the
      size of glycosaminoglycan chains released from proteoglycan as measured by
      alkaline borohydride treatment, ruling out (b). Disaccharide analysis by HPLC
      after chondroitin sulfate ABC digestion revealed that glycosaminoglycan mainly
      contains monosulfated chondroitin disaccharides and that oversulfation was not
      observed under the influence of IL-1 beta or TGF-beta, ruling out (d). The
      capacity to synthesize glycosaminoglycan chain in the presence of an artifical
      acceptor of chain elongation, beta-D-xylodide, was increased significantly by IL
      1 beta but not obviously so by TGF-beta.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7804448
TI  - Insulin, insulin-like growth factor I (IGF-I) and IGF-II enhance basal and
      gonadotrophin-releasing hormone-stimulated luteinizing hormone release from rat
      anterior pituitary cells in vitro.
AB  - The role of insulin-like growth factor I (IGF-I) and IGF-II on luteinizing
      hormone (LH) release is still unclear. The present study was performed to
      investigate modifications of basal and gonadotrophin-releasing hormone (GnRH)
      stimulated (10(-9) mol/l) LH release, induced by 4-h and a 24-h incubation with
      physiological doses of IGF-I (1, 5 and 10 nmol/l) and IGF-II (5, 10 and 15
      nmol/l) in comparison with insulin (0.0017, 0.1722 and 1.722 nmol/l), from
      primary cultures of male rat anterior pituitary cells. Both during the 4-h and
      the 24-h incubation, basal and GnRH-stimulated LH release were increased by IGF
      I, IGF-II and insulin in a dose-dependent fashion. Present data confirm insulin's
      capability of potentiating anterior pituitary LH release from dispersed rat
      anterior pituitary cells in vitro, and reveal similar effects for physiological
      doses of IGF-I and IGF-II.

PMID- 7804449
TI  - Involvement of protein kinase C in the stimulation of sodium-dependent phosphate
      transport by parathyroid hormone in osteoblast-like cells.
AB  - The rat osteosarcoma cell line UMR-106 has an osteoblast-like phenotype and
      possesses parathyroid hormone (PTH)-responsive dual signal transduction systems
      [adenosine 3',5'-cyclic monophosphate-dependent protein kinase (PKA) and calcium
      protein kinase C (Ca-PKC)]. These cells transport inorganic phosphate (Pi) by a
      Na(+)-dependent carrier under stimulation by PTH. The present study aimed to
      clarify PTH-responsive signal transduction mechanisms in the regulation of Na(+)
      dependent Pi transport by PTH in UMR-106 cells. Exposure of these cells to 10(-7)
      mol/l PTH induced a significant increase in Pi uptake within 30 min of incubation
      and it became maximal after 2 h. Parathyroid hormone (10(-9)-10(-7) mol/l)
      stimulated Pi uptake dose dependently. Activation of PKC by 12-O-tetradecanoyl
      phorbol-13-acetate (TPA) also increased Pi uptake in time- and dose-dependent
      manners similar to PTH. In contrast, neither PKA activation by 10(-4) mol/l
      forskolin or by 10(-4) mol/l dibutyryladenosine 3',5'-cyclic monophosphate nor
      calcium ionophore treatment with 10(-7) mol/l A23187 or with 10(-7) mol/l
      ionomycin during 3-h incubations affect Pi uptake, except its increase by 10(-4)
      mol/l forskolin at a 3-h incubation. These agents had no influence on Pi uptake
      even in combined treatments with TPA. The PTH-induced increase in Pi uptake was
      abolished almost completely by pretreating cells with PKC inhibitors, 1-(5
      isoquinolinylsulfonyl)-2-methylpiperazine dihydrochloride (H-7) (50 mumol/l) or
      staurosporin (10 and 50 nmol/l), and by down-regulating PKC with a prolonged TPA
      treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7804450
TI  - Effects of deflazacort and cortisone on body growth, thymus weight and gene
      expression of growth-related proteins in the rat.
AB  - Deflazacort is an oxazoline derivative of cortisone with presumably less serious
      side effects, but its effects on growth factors are unknown. The present
      experiments in Long Evans rats were carried out to investigate how deflazacort
      administration affected the growing rat, especially in relation to hepatic
      insulin-like growth factor I (IGF-I) and growth hormone receptor (GHR) messenger
      ribonucleic acid (mRNA). Four groups of animals were used: those treated with
      cortisone, with two different doses of deflazacort and with vehicle. Subcutaneous
      injections were given daily for 8 days. Thymus weight was reduced in all treated
      groups, with a comparable magnitude of reduction in the groups treated with
      cortisone and the higher dose of deflazacort (DF1). Daily weight gain was reduced
      significantly after cortisone treatment, but less so in the DF1 rats. Liver IFG-I
      and GHR mRNA were lower in the cortisone and deflazacort than in controls.
      However, GHR mRNA was reduced significantly only by cortisone and not by DF1. We
      conclude that growth failure is less severe in the DF1 rats compared to cortisone
      rats, which corresponds to the reduction in hepatic GHR mRNA.

PMID- 7804452
TI  - Neuromuscular diseases: nerve.

PMID- 7804451
TI  - Effect of 6-hydroxydopamine injection into the arcuate hypothalamic nucleus on
      the osmotic release of vasopressin in conscious rats.
AB  - The aim of the present study was to evaluate a role in vasopressin secretion of
      the catecholaminergic neurons, including the tuberohypophysial dopaminergic
      neurons situated in the arcuate hypothalamic nucleus. A neurotoxin, 6
      hydroxydopamine (6 g/l), was injected locally into the arcuate nucleus and its
      effects on catecholamine levels of the hypothalamic tissue and the
      neurointermediate lobe, and on the plasma vasopressin concentrations before and
      during i.v. infusion (0.1 ml kg-1 min-1) of isotonic (0.15 mol/l) or hypertonic
      saline (2.5 mol/l), were examined in conscious rats. The infusion of hypertonic
      saline produced increases of plasma vasopressin 15 and 30 min later, accompanied
      by elevations of plasma osmolality, sodium, chloride and arterial pressure. The
      vasopressin response was potentiated markedly by the 6-hydroxydopamine injection
      performed 8 days before, which hardly affected the responses of the other
      variables. Histological examination indicated that the injection sites of 6
      hydroxydopamine in those rats had been located in the area ranging from rostral
      to medial arcuate nucleus. The i.v. infusion of isotonic saline did not change
      plasma vasopressin, osmolality, sodium, chloride or arterial pressure, regardless
      of the presence or absence of pretreatment with 6-hydroxydopamine. It was
      confirmed that when 6-hydroxydopamine was injected into the arcuate nucleus
      region 8 days before, noradrenaline and adrenaline concentrations of the
      hypothalamic tissue containing the injection site were decreased remarkably,
      although we could not detect any significant alteration in the dopamine
      concentration of the hypothalamic tissue or the neurointermediate lobe. On the
      basis of these results, we concluded that catecholaminergic neurons in the
      arcuate nucleus may act to inhibit osmotic vasopressin secretion.

PMID- 7804453
TI  - Neuromuscular diseases: muscle.

PMID- 7804454
TI  - Neuromuscular diseases: nerve.

PMID- 7804455
TI  - Inherited neuropathies.
AB  - Charcot-Marie-Tooth neuropathy (CMT) type 1 is a genetically heterogeneous group
      of chronic demyelinating polyneuropathies with loci mapping to chromosome 17
      (CMT1A), chromosome 1 (CMT1B), the X chromosome (CMTX), and to another unknown
      autosome (CMT1C). CMT1A is most often associated with a tandem 1.5-Mb duplication
      in chromosome 17p11.2-12, or in rare patients may result from a point mutation in
      the peripheral myelin protein-22 (PMP22) gene. CMT1B is associated with point
      mutations in the myelin protein zero (P0) gene. The molecular defect in CMT1C is
      unknown. CMTX is associated with mutations in the connexin 32 gene. CMT2 is an
      axonal neuropathy of undetermined cause. One form of CMT2 maps to chromosome 1p36
      (CMT2A). Dejerine-Sottas disease is a severe, infantile-onset demyelinating
      polyneuropathy that may be associated with point mutations in either the PMP22
      gene or the P0 gene. Hereditary neuropathy with liability to pressure palsies
      (HNPP) is a recurrent, episodic demyelinating neuropathy. HNPP is associated with
      a 1.5-Mb deletion in chromosome 17p11.2-12 and may result from reduced expression
      of the PMP22 gene. Most examples of CMT1A and HNPP are reciprocal duplication or
      deletion syndromes originating from unequal crossover during germ cell meiosis.
      Familial amyloid polyneuropathy (FAP) is an autosomal dominant disorder that
      classically presents with a sensory peripheral neuropathy and early autonomic
      involvement. Transthyretin (TTR) is the most common constituent amyloid fibril
      protein deposited in FAP, and there are now 28 point mutations in the TTR gene
      described in TTR-related FAP. Liver transplantation looks promising as a
      treatment for TTR-related FAP.

PMID- 7804456
TI  - Diabetic neuropathy.
AB  - It has been generally accepted that diabetic neuropathy is associated with
      substantial morbidity and increased mortality, and that aldose reductase
      inhibitors are of potential therapeutic value, whereas the beneficial effect of
      strict insulin treatment is questionable. Contrary to these expectations,
      population-based studies now report only 6% occurrence of severe neuropathy among
      insulin-dependent diabetes mellitus patients. Also, intensified insulin treatment
      preserved conduction velocity for 5 years in a large group of insulin-dependent
      diabetes mellitus patients and reduced neuropathy development by 60%, whereas
      studies on aldose reductase inhibitors failed to produce any convincing
      therapeutic effect.

PMID- 7804457
TI  - Guillain-Barre syndrome.
AB  - Guillain-Barre syndrome has now become recognized as a clinical syndrome that may
      be due to several pathological entities, consisting of an acute inflammatory
      demyelinating polyradiculoneuropathy as well as an acute motor axonal neuropathy.
      Campylobacter jejuni infection is a common preceding event and, together with
      anti-ganglioside GM1 antibodies, is associated with axonal damage and a poor
      outcome. The mechanism by which such antibodies damage axons is not clear. The
      Miller Fisher syndrome is very closely associated with antibodies to ganglioside
      GQ1b that may be important in pathogenesis. Treatment of Guillain-Barre syndrome
      with intravenous immunoglobulin appears to be as effective as plasma exchange in
      one controlled trial. Two small series have reported a high incidence of early
      relapses following intravenous immunoglobulin, and its efficacy is being
      reexamined in a further controlled trial.

PMID- 7804458
TI  - Chronic inflammatory demyelinating polyneuropathy and paraproteinemic
      neuropathies.
AB  - Chronic inflammatory demyelinating polyneuropathy and the neuropathies associated
      with monoclonal gammopathies represent a significant proportion of initially
      undiagnosed neuropathies. Over the past year, a number of publications have
      provided information on the clinical characteristics, mechanisms, and possible
      relationships between these neuropathies. This review summarizes this recent
      information, with an emphasis on the relevance to therapy.

PMID- 7804459
TI  - Infective neuropathies.
AB  - Infective neuropathies encompass neuropathies that are among the most common in
      the world. Retroviral infection, which includes infection with the human
      immunodeficiency virus, has now spread worldwide. This virus is responsible for a
      number of disabling peripheral neuropathies, either from the immune reaction that
      follows penetration of the virus into nervous system of the host, or by
      opportunistic infection secondary to the major cellular immunodeficit induced by
      gradual destruction of lymphocytes bearing the CD4 antigen on their surface. In
      the other class of retroviruses, human T lymphotrophic viruses (HTLV), which are
      responsible for the HTLV-I-associated myelopathy or tropical spastic paraparesis,
      peripheral nerve involvement and inflammatory myopathy are less common and milder
      than in HIV infection. Leprosy continues to pose problems concerning the
      understanding of the immune mechanisms that lead to the various patterns of nerve
      lesions encountered in this condition. Chagas' disease, which is due to infection
      with Trypanosoma cruzi, affects more than 15 million people in Latin America. It
      is accompanied by mostly subclinical peripheral nerve involvement and by cardiac
      manifestations from lesions of the autonomic nervous system and cardiac muscle.

PMID- 7804460
TI  - Autonomic neuropathies.
AB  - There is a spectrum of acute autonomic neuropathies. Acute panautonomic
      neuropathy (pandysautonomia), characterized by severe widespread sympathetic and
      parasympathetic failure, is at one extreme. Guillain-Barre syndrome is at the
      other end of the spectrum, where the brunt of the disorder falls on the somatic
      nervous system. Pure acute panautonomic neuropathies are relatively rare. The
      majority of acute autonomic neuropathies have some minor somatic features.
      Dysautonomia may be restricted to the cholinergic system (acute cholinergic
      neuropathy), adrenergic system, or other organ systems (eg, motility disorders).
      Recently, an important gap in the clinical description of idiopathic autonomic
      neuropathies and their course was filled, with neurologic and autonomic testing
      end-points. About one in four to one in three patients will improve
      substantially. Two other manifestations of autonomic neuropathy are the
      pseudoobstruction and postural tachycardia syndromes. Loss of the baroreceptors
      and consequent impairment of buffering of blood pressure results in wild swings
      in blood pressure that are treatable. Correcting anemia improves orthostatic
      tolerance, if necessary by hemopoietin. Improved evaluation of neural structure,
      in skin and in the laboratory, has led to better quantitation of autonomic
      failure and mechanisms of syncope. This understanding has been extended to the
      frequency domain and to a study of cerebral vasoregulation.

PMID- 7804461
TI  - Pain mechanisms in neuropathy.
AB  - Current opinion on "neuropathic" pain is chaotic and divided. This review is a
      summary attempt at describing the principal hypotheses that are currently
      entertained and at interpreting the basic underlying mechanisms of these pains.
      Rather than relying preferentially on rigorous data generated from
      neurophysiological animal experimentation, reasonable priority is given to
      evidence derived from rigorous neurophysiological and psychophysical studies in
      human volunteers and patients. Issues such as the concept of "centralization" of
      neuropathic pain mechanisms, which dwell excessively upon extrapolation from
      animal experiment to human clinical reality, are highlighted as questionable.
      Psychogenic pseudoneuropathy, an entity of high clinical prevalence and low
      appreciation by basic scientists and the reflex sympathetic dystrophy
      establishment, is also given the emphasis it deserves.

PMID- 7804462
TI  - Peripheral nerve injury.
AB  - Knowledge of the actions of conventional neurotrophic factors on peripheral
      neurons is accumulating rapidly, and growth factors that were discovered outside
      the nervous system have been found to have neurotrophic actions. The nature and
      initiation of proximal neuronal responses to nerve injury, the interactions of
      Schwann cells and growth cones, and the functions of macrophages in the
      peripheral nervous system are all areas of active investigation. Results of the
      surgical treatment of injuries to the brachial plexus and spinal accessory nerve
      are reported.

PMID- 7804463
TI  - Developing new treatments for muscle disease: prospects and promise.

PMID- 7804464
TI  - Potential for growth factor treatment of muscle disease.
AB  - The recent development of recombinant human growth hormone (GH) and insulin-like
      growth factor 1 (IGF-1) has provided the opportunity to study the effects of
      these growth factors in humans. The majority of studies have been performed in
      healthy young and older adults. Both GH and IGF-1 have shown very positive
      effects on muscle protein anabolism. Relatively few side effects have developed.
      Initial studies have shown a beneficial effect of GH in reversing the catabolic
      actions of oral prednisone, and GH treatment has led to an increase in muscle
      mass and protein synthesis in pilot studies of myotonic dystrophy. Combination
      therapy in normal subjects using both GH and IGF-1 has shown encouraging results.
      There is a greater enhancement of protein anabolism during combined treatment
      than there is with either agent alone, and concomitant therapy with GH diminished
      the side effects of IGF-1. It is now feasible to consider therapeutic trials in
      patients. Future studies of GH and IGF-1 treatment in patients with primary
      muscle disease and in patients receiving long-term corticosteroid therapy are
      needed.

PMID- 7804465
TI  - The impact of molecular genetics on the care of patients with muscle disease.
AB  - Clinical medicine is currently undergoing an enormous upheaval as a result of
      molecular genetics. Identifying the gene causing a specific disease almost
      immediately provides knowledge of the gene product and insight into pathogenesis.
      Mutations of the gene and measurable abnormalities of the gene product provide
      specific methods for diagnosis, prenatal counseling, and carrier detection.
      Perhaps, most importantly, new treatment strategies can be devised. In the review
      that follows, an update is provided on molecular findings in muscle diseases and
      how they can be applied in clinical practice.

PMID- 7804466
TI  - Idiopathic inflammatory myopathies: inclusion-body myositis, polymyositis, and
      dermatomyositis.
AB  - In this review, the main emphasis is on new advances concerning sporadic
      inclusion-body myositis and hereditary inclusion-body myopathy. Polymyositis and
      dermatomyositis are reviewed briefly. Hypotheses are presented regarding the
      possible cause and significance of abnormally accumulated beta-amyloid protein,
      two other epitopes of beta-amyloid precursor protein, hyperphosphorylated tau,
      alpha 1-antichymotrypsin, ubiquitin, and prion protein in sporadic inclusion-body
      myositis and hereditary inclusion-body myopathy. Because most of those proteins
      are also accumulated at the neuromuscular junction, "junctionalization" of other
      muscle fiber nuclei is a possibility. Attention is given to the fact that
      vacuolated muscle fibers in hereditary inclusion-body myopathy may represent
      early changes because they are virtually free of congophilic amyloid deposit but,
      like sporadic inclusion-body myositis, contain large accumulations of beta
      amyloid protein and prion.

PMID- 7804467
TI  - Mitochondrial diseases of muscle.

PMID- 7804468
TI  - Gene therapy for muscle diseases.
AB  - Duchenne muscular dystrophy involves progressive degeneration of the skeletal and
      cardiac muscles, resulting in premature death. A number of methods are currently
      being developed for the treatment of Duchenne muscular dystrophy and other
      neuromuscular disorders. A number of the viral vector systems, myoblast transfer,
      and direct injection techniques that are currently under investigation for the
      treatment of neuromuscular disorders are reviewed here.

PMID- 7804469
TI  - Factors controlling muscle protein synthesis and degradation.
AB  - Insulin is a well-known anabolic hormone. The mechanism of insulin's protein
      anabolic effect remains controversial. Although insulin undoubtedly inhibits
      protein degradation, its effect on protein synthesis is incompletely defined.
      Recent studies reviewed in this article highlight the methodologic limitations in
      studying the effect of insulin on protein synthesis. These methodological issues
      are related to the hypoaminoacidemia that ensues after insulin administration and
      to the difficulty in measuring the obligatory precursor pool (aminoacyl tRNA)
      label. Differential responses to unweighing in different muscle proteins has been
      demonstrated. The protein loss during unweighing is due to the loss of
      myofibrillar proteins, although sarcoplasmic proteins are spared. A recent study
      has found that lipid emulsion has no effect on whole protein degradation but
      decreases forearm protein degradation and synthesis. Age-related muscle wasting
      in humans has been shown to be related to a decline in fractional myofibrillar
      protein synthesis rate. Although some progress has been made by recent studies,
      refined methodologies are needed to define the regulation of muscle protein
      turnover in humans.

PMID- 7804470
TI  - The effects of psychological research on the continuity of the patient-physician
      relationship in a primary care health maintenance organization setting.
AB  - This project was designed to explore the impact of sensitive psychological
      research on the continuity of the relationship between the patient and the
      physician researcher in a primary care health maintenance organization setting.
      Subjects were 134 women who participated in a sensitive psychological research
      project that was conducted by a female family physician researcher. Subjects were
      matched by height and weight, length of the study interval, and type of medical
      service with 127 female controls who were seen by a male family physician during
      the same period in the same health maintenance facility. Participants were
      compared for patient-initiated changes in primary care physicians during
      equalized follow-up periods. No significant differences between subjects and
      controls were found. These results suggest that sensitive psychological research
      does not appear to deter patients who are research participants from continuing
      their professional relationship with the physician researcher.

PMID- 7804471
TI  - Dissemination of information about the US Preventive Service Task Force
      guidelines.
AB  - We assessed the familiarity of family physicians with the US Preventive Service
      Task Force guidelines and targeted groups for interventions to increase the
      practice of recommended preventive services. A national random sample of 480
      family physicians were mailed a survey consisting of demographic items and a
      question regarding their level of exposure to the guidelines. The association of
      demographic factors with the level of exposure was assessed. Of the 263
      responding physicians, 37% reported that they had not read any of the
      recommendations. Physicians who had read at least some of the recommendations
      were younger, more recently graduated from medical school, less likely to be in
      solo practice, more likely to be residency trained, and more likely to be white.
      Only year of graduation and race remained significantly associated with exposure
      to the guidelines in a logistic regression model. Additional dissemination
      efforts should focus on solo practitioners, less recent graduates, and nonwhite
      physicians.

PMID- 7804472
TI  - Pathology in family practice. Chronic bullous disease of childhood.

PMID- 7804473
TI  - Headache classification.

PMID- 7804474
TI  - Diabetes mellitus management 'PENTAD'.

PMID- 7804475
TI  - Assessing consumer expectations and patient satisfaction. Passing fad, mission
      impossible, or 'just what the doctor ordered'?

PMID- 7804476
TI  - The physician's role. Views of the public and the profession on seven aspects of
      patient care.
AB  - OBJECTIVES: To determine the importance of various areas of physician competency
      and to assess the public's ratings of their own physicians. DESIGN: A nationwide
      household telephone survey. PARTICIPANTS: A random sample of 640 US adults (61%
      response rate). MAIN OUTCOME MEASURES: Ratings of importance and physicians'
      competencies in diagnosing and treating illness, communication, ethical conduct,
      cooperation with other health care professionals, promotion of preventive care,
      use of technology, and consideration of the cost of care to the patient. RESULTS:
      Physicians were rated lowest on communication skills and on attention to the
      costs of the recommended treatment. A comparison of the results with a similar
      survey of physicians shows that physicians rate their training the lowest in
      these same areas. Physicians in general practice were rated lower on several
      competencies than were other physicians. CONCLUSIONS: Health care consumers and
      physicians share similar values about what is important in the role of a
      physician. In the areas of communication and attention to the costs of treatment,
      public needs are not always being met.

PMID- 7804477
TI  - Psyllium for the reduction of cholestyramine-associated gastrointestinal symptoms
      in the treatment of primary hypercholesterolemia.
AB  - OBJECTIVE: To determine if the bulk-forming laxative, psyllium hydrophilic
      mucilloid (PHM), reduces the gastrointestinal side effects and enhances the
      cholesterol-lowering efficacy of cholestyramine resin in patients with primary
      hypercholesterolemia. DESIGN: After a dietary lead-in period and 6 weeks of
      treatment with cholestyramine, the study followed a double-blinded, placebo
      controlled, crossover format. SETTING: Lipid clinic affiliated with a large
      metropolitan community hospital. PARTICIPANTS: Twenty-seven randomly selected
      male and female patients with a diagnosis of primary hypercholesterolemia. Entry
      criteria required a fasting low-density lipoprotein cholesterol (LDL-C)
      concentration of 4.91 mmol/L (190 mg/dL) or greater and a triglyceride
      concentration of less than 2.26 mmol/L. Patients using steroids, beta-blockers,
      thiazide diuretics, and lipid-lowering agents, or having a history of allergy to
      psyllium or aspartame were excluded. INTERVENTION: The study consisted of four
      interventional phases of 6 weeks' duration that included (1) dietary
      stabilization (National Cholesterol Education Program Step I Diet); (2)
      cholestyramine therapy (4 g twice daily); (3) cholestyramine with study
      medication (PHM [5.1 g twice daily] or placebo); and (4) cholestyramine with
      crossover to alternate study medication. MAIN RESULTS: Following the 6-week
      dietary lead-in phase, four patients were eliminated from the study because their
      fasting LDL-C concentrations fell below 4.14 mmol/L (160 mg/dL), and one patient
      was eliminated because testosterone therapy was initiated by his internist. The
      remaining 22 patients entered the cholestyramine treatment phase. Four left the
      study within 2 weeks because of intolerable gastrointestinal tract symptoms. The
      18 patients who completed this phase demonstrated significant reductions in their
      plasma total cholesterol (7.27 vs 6.67 mmol/L [281 vs 258 mg/dL]) and LDL-C (5.38
      vs 4.63 mmol/L [208 vs 179 mg/dL]) concentrations compared with baseline levels.
      The addition of PHM to the cholestyramine regimen provided a tendency toward
      further reductions in total cholesterol and LDL-C levels (6.67 vs 6.46 mmol/L
      [258 vs 250 mg/dL] and 4.63 vs 4.29 mmol/L [179 vs 166 mg/dL], respectively),
      although statistical significance was not achieved. Psyllium hydrophilic
      mucilloid significantly reduced the frequency and severity of constipation,
      abdominal discomfort, and heartburn. No reports of new gastrointestinal tract
      symptoms or untoward effects were noted with the addition of PHM. CONCLUSION:
      These data suggest that the addition of PHM to cholestyramine therapy may improve
      a patient's compliance by reducing the associated gastrointestinal tract side
      effects.

PMID- 7804478
TI  - Patients' interpretation of qualitative probability statements.
AB  - BACKGROUND: Physicians often use qualitative probability statements to compare
      treatment options or describe risks of treatment, especially if exact numerical
      information is not readily available. OBJECTIVES: To determine (1) the effect of
      context, experience, age, gender, race, occupation, and education on patients'
      numerical interpretation of probability terms and (2) patient preferences for
      information about side effects (qualitative or numerical). DESIGN: Cross
      sectional survey. SETTING: A university-based family practice in Ann Arbor, Mich.
      PARTICIPANTS: Patients 18 years of age and older and parents of patients younger
      than 18 years of age seen during January and February 1993 for any reason except
      complete physical examination. METHODS: A questionnaire presented scenarios of
      minor and major complications related to four different medical conditions.
      Participants were asked to estimate how many people of 100 would have a
      complication if their physician described the risk for the complication in each
      scenario as unlikely. Participants were then asked whether they preferred
      receiving information from their physician about the risk for complications in
      words or numbers. RESULTS: Of 345 questionnaires distributed, 307 patients (89%)
      completed them. The rates assigned to the minor complications were significantly
      higher than the rates assigned to the major complications (P = .0001).
      Participants who had experienced the described complication reported
      significantly higher rates for the minor complications of vaccination and surgery
      (P = .0001 and P = .0235, respectively). Education had a significant effect only
      on the rates assigned to vaccination complications (P = .0069). Occupation had a
      significant effect only on the rates assigned to antibiotic side effects (P =
      .0090). CONCLUSIONS: When a physician uses qualitative probability statements, he
      or she must be sensitive to the patient's previous experience with that procedure
      or medication. Also, if one wants to convey the same potential rate of occurrence
      for major and minor side effects, then one needs to use different words for each.

PMID- 7804479
TI  - Feasibility and potential clinical usefulness of a computerized severity of
      illness measure.
AB  - OBJECTIVE: To assess the feasibility and potential clinical usefulness of the
      computerized Duke Severity of Illness Checklist (DUSOI). DESIGN: Cross-sectional
      study of patients whose severity of illness was measured with the DUSOI.
      Providers assessed the clinical usefulness of the DUSOI and recorded the length
      of time required for rating severity. Auditors rated severity using progress note
      information. Demographic and financial data from clinic records were also
      obtained. SETTING: University-based family practice clinic with 64,621 annual
      visits. PATIENTS: Convenience sample of ambulatory patients. MAIN OUTCOME
      MEASURES: Clinical usefulness and time required to rate severity. RESULTS: For
      117 patients (63.3% female; mean age, 46.3 years), the mean charge was $105.38,
      the mean number of health problems was 2.0, the mean overall provider DUSOI score
      was 33.7, and the mean auditor DUSOI score was 34.0 (scale = 0 to 100). There was
      excellent agreement between provider and auditor DUSOI scores (intraclass
      correlation coefficient, .77). Providers required 1.1 minutes to record severity;
      the principal auditor required 1.6 minutes. Providers found the DUSOI potentially
      useful in 30.3% of patients. Usefulness was greater in women (38.2% of women vs
      18.2% of men), older patients (mean age, 54.5 years in useful group vs 41.9 in
      nonuseful group), and sicker patients (mean DUSOI score, 55.1 vs 25.9). The DUSOI
      was more clinically useful in patients with health problems such as type II
      diabetes mellitus (75.0%) than in those with problems such as tobacco use
      (25.0%). Higher charges correlated with a higher number of health problems and
      with female gender but not with severity scores. CONCLUSIONS: The computerized
      DUSOI is feasible for all patients and is potentially useful for women, older,
      and sicker patients.

PMID- 7804480
TI  - A critical review of the new oral cephalosporins. Considerations and place in
      therapy.
AB  - Oral cephalosporins are key antimicrobials in the family physician's therapeutic
      armamentarium. The list of available agents within this class has been recently
      expanded to include cefixime, cefprozil, cefpodoxime proxetil, and loracarbef.
      Each of these antibiotics has differing antimicrobial coverage patterns and
      approved therapeutic uses. Compared with older, more established antimicrobials
      such as penicillin, amoxicillin, cefaclor, a combination of amoxicillin and
      clavulanate potassium, and erythromycin, the newer cephalosporins offer little,
      if any, therapeutic advantage. Clinical efficacy has been shown to be equal in
      virtually all studies comparing the newer cephalosporins with traditional agents
      for various community-acquired infections. While the four newer agents may be
      given less often, they are relatively expensive. In light of the available
      clinical data, the newer oral cephalosporins should be reserved as second- or
      third-line choices.

PMID- 7804481
TI  - Common hand fractures in family practice.
AB  - This article describes the office treatment for five common hand fractures. In
      addition to examination findings and treatment options, guidelines are provided
      for those complications that necessitate orthopedic referral. The five fractures
      reviewed include mallet finger fractures, distal phalangeal fractures, fractures
      from volar plate injuries to the middle phalanx, dorsal dislocations of the
      proximal interphalangeal joint, and fractures of the fifth metacarpal.

PMID- 7804482
TI  - Human immunodeficiency virus early intervention physician guidelines, second
      edition. Advisory Group on HIV Early Intervention, Second Edition, American
      Medical Association.
AB  - An estimated 1 million people in the United States are presently infected with
      the human immunodeficiency virus (HIV). Each of these individuals should be under
      the care of a physician. Moreover, there is general consensus that early
      intervention should be managed in the primary care setting. Primary care
      physicians are well suited to manage the total treatment of persons with HIV
      throughout the disease process. These guidelines provide the primary care
      physician with the information to diagnose HIV infection, determine disease
      stage, and monitor and treat patients during early stages of infection. The
      guidelines also provide referral to sources of additional information and HIV
      training.

PMID- 7804484
TI  - Pharmaceutical marketing.

PMID- 7804483
TI  - Pharmaceutical advertising: the FDA does not protect us.

PMID- 7804485
TI  - Is pharmaceutical marketing valuable?

PMID- 7804486
TI  - Value and need for pharmaceutical promotion disputed.

PMID- 7804487
TI  - Pharmacoeconomic considerations in pharmaceutical company promotions.

PMID- 7804488
TI  - A comparative study of eight fecal occult blood tests and HemoQuant in patients
      in whom colonoscopy is indicated.
AB  - BACKGROUND AND OBJECTIVE: Some studies suggest that immunochemical fecal occult
      blood tests (FOBTs) and HemoQuant are more efficient at detecting fecal occult
      blood than the commonly employed Hemoccult II (guaiac) test. We undertook this
      study to determine whether an immunochemical test either alone or in combination
      with a guaiac test gives efficiency superior to the Hemoccult II test in
      predicting significant gastrointestinal tract disease. DESIGN: Criterion
      standard, prospective, blinded. SETTING: Referral population of ambulatory
      patients at an institutional and a private hospital. PATIENTS: Eight-one patients
      referred to a gastroenterologist and in whom colonoscopy was indicated.
      INTERVENTIONS: While on a restricted diet, patients made preparations for FOBTs
      from three consecutive bowel movements. Patients then underwent colonoscopy.
      Polyps larger than 1 cm in size, carcinoma of the colon, peptic ulcers, gastric
      erosions, and angiodysplasia were considered to be likely causes of occult
      gastrointestinal tract bleeding. MAIN OUTCOME MEASURES: Using colonoscopy results
      as the reference standard, sensitivity, specificity, and positive and negative
      predictive values for each of eight tests or pair of tests were compared with
      those of Hemoccult II. RESULTS: Of 81 patients, 10 had significant lower
      gastrointestinal tract lesions and six had significant upper gastrointestinal
      tract lesions. Hemoccult SENSA, Heme-Select, and FECA-EIA were shown to be more
      sensitive than Hemoccult II but slightly less specific. Paired tests showed less
      efficiency than Hemoccult II alone. CONCLUSIONS: We did not find an ideal test or
      pair of tests; however, Hemoccult SENSA exhibited higher sensitivity than
      Hemoccult II and many other tests. The sensitivity, specificity, and positive
      predictive values of many of the FOBTs were believed to be low. We recommend that
      physicians consider FOBTs only as adjuncts to history and physical examination
      findings in deciding how to proceed in diagnosing gastrointestinal tract disease.

PMID- 7804489
TI  - Outcome of 48 pediatric patients with chronic fatigue. A clinical experience.
AB  - OBJECTIVE: To define outcomes of pediatric patients with chronic fatigue. DESIGN:
      Cohort study with a mean follow-up of 3.8 years. SETTING: Outpatient pediatrics
      department at a university health center. PATIENTS: Patients 21 years old and
      younger referred by their private physicians for evaluation of unexplained
      fatigue lasting at least 3 months. INTERVENTION: Patients were seen from January
      1986 through April 1990 and were telephoned in April 1992 to determine outcome.
      RESULTS: Of the 55 patients who were evaluated from 1986 to 1990, an organic
      cause of the fatigue, sinusitis, was found for one. Of the 54 patients with
      unexplained fatigue, 48 were contacted in 1992. The mean age of these 48 patients
      was 15 years; 73% were female. Fatigue was present a mean of 7 months before
      evaluation, and in 78% an acute illness preceded the fatigue. Most patients
      believed their fatigue had an organic cause. In general, laboratory studies were
      not helpful. All patients were encouraged to resume normal functioning despite
      their symptoms. At follow-up, 65% reported resolution of symptoms, 29% reported
      improvement, and 6% were unchanged. CONCLUSIONS: In pediatric patients with
      chronic fatigue, diagnostic and therapeutic interventions should be based on
      positive findings; with simple encouragement, the prognosis is excellent. Based
      on this experience, we suggest a structured approach to the management of
      pediatric patients with chronic fatigue.

PMID- 7804490
TI  - Elderly outpatients' understanding of a physician-initiated advance directive
      discussion.
AB  - OBJECTIVE: To examine elderly outpatients' understanding of advance directives
      (ADs), cardiopulmonary resuscitation (CPR), and artificial nutrition and
      hydration (ANH) with and without the benefit of a physician-initiated discussion.
      DESIGN: Randomized controlled trial. SETTING: University-affiliated, community
      based, urban family practice residency training program. PATIENTS: One hundred
      patients aged 65 and older, consecutively sampled and randomly assigned to one of
      two discussion groups. INTERVENTIONS: Physicians' discussions based on a prepared
      script consisting of AD issues or health promotion issues. MAIN OUTCOME MEASURES:
      Test of comprehension of AD, CPR, and ANH information, using open-ended and yes
      or-no questions. RESULTS: Patients in the AD and health promotion discussion
      groups showed good basic understanding. Younger and better-educated patients had
      a better working knowledge of AD-related information. Understanding of ADs was
      higher when the physician spent more time talking about AD-related issues after
      the discussion was completed. CONCLUSIONS: Many elderly outpatients have a good
      basic understanding of ADs, CPR, and ANH, even without explicit explanations from
      physicians. However, younger, better-educated patients and those who had longer
      unstructured discussions had greater AD-related knowledge. These factors need to
      be considered when framing discussions with patients about ADs and life
      sustaining treatments.

PMID- 7804491
TI  - Clinician specialty and treatment style for depressed outpatients with and
      without medical comorbidities.
AB  - BACKGROUND: The advent of clinical practice guidelines for the management of
      depression increases the importance of understanding variation across clinician
      specialty groups in treatment styles for depression and the role of medical
      comorbidities. METHODS: Data are reported by clinicians (N = 470) and patients (N
      = 2545). Multiple regression was used to compare the treatment styles (counseling
      and prescribing antidepressants) of family physicians with those of
      psychiatrists, medical subspecialists, internists, psychologists, and other
      therapists for depressed patients with different medical comorbidities. RESULTS:
      Relative to other primary care specialists, family physicians had the strongest
      preferences for both counseling and prescribing antidepressants for depressed
      patients. Family physicians reported preferences for treating with
      antidepressants that were similar to those of psychiatrists. However, in actual
      practice, medication use was higher among the patients of psychiatrists than
      those of family physicians. Mental health care specialists reported the strongest
      counseling preferences and provided the most counseling in actual practice,
      compared with general medicine physicians. Internists and subspecialists had
      similar preferences for prescribing antidepressants, but, compared with
      internists, subspecialists had lower preferences for counseling. Clinician
      preferences for counseling were similar for depressed patients with or without
      medical comorbidities, but preferences for prescribing antidepressants were
      lowest for patients with depression and myocardial infarction, compared with
      other patient groups. CONCLUSIONS: Measures of clinician treatment style for
      depression are good proxies for counseling but not for prescribing practices.
      Among general medical physicians, family physicians have the strongest reported
      preferences in treating depression but, especially in terms of medication
      therapy, do not always follow those preferences. Preferred treatments of patients
      with and without medical comorbidities were similar. Findings have implications
      for improving the quality of treatment of depressed patients.

PMID- 7804492
TI  - Dietitian practices for adult outpatients with hypercholesterolemia referred by
      physicians. The Minnesota Dietitian Survey.
AB  - OBJECTIVE: To characterize the physician-to-dietitian referral process and
      dietitian practice patterns and opinions related to adult outpatients with
      hypercholesterolemia. DESIGN: Cross-sectional mail survey. PARTICIPANTS:
      Minnesota dietitians who treat adult outpatients referred by physicians for
      hypercholesterolemia. MAIN OUTCOME MEASURES: Proportion of patients for whom
      background information or specific diet instructions were provided by referring
      physicians and for whom follow-up was recommended and dietary fat content
      calculated by the dietitians. RESULTS: Completed questionnaires were returned by
      216 of 267 eligible dietitians (81% response rate). Respondents saw, on average,
      31 referred patients per month, 31% of whom were referred for
      hypercholesterolemia, 31% for type II diabetes mellitus, and 24% for obesity. For
      patients referred for hypercholesterolemia, background information was provided
      by physicians 37% of the time, and specific diet instructions 15% of the time.
      One or more follow-up visits by the dietitians were recommended for 42% of
      patients referred for hypercholesterolemia, compared with 60% and 70% of patients
      referred for diabetes and obesity, respectively. The average number of additional
      visits within 6 months of the initial consultation recommended by dietitians was
      2.0 for patients referred for hypercholesterolemia, 3.5 for patients referred for
      diabetes, and 6.7 for patients referred for obesity, and the number of visits
      that occurred was half or less than that recommended. Dietary fat content was
      calculated by the dietitians for only 25% of patients referred for
      hypercholesterolemia. CONCLUSIONS: For adult outpatients referred to dietitians
      for hypercholesterolemia, relevant patient information is usually not provided by
      referring physicians, the number of follow-up visits is well below what would
      reasonably be expected to produce significant and sustained eating behavior
      change, and calculation of dietary fat content is generally not done. More
      research is needed to determine appropriate nutrition intervention protocols for
      these patients.

PMID- 7804493
TI  - Minor depression and functional impairment.
AB  - OBJECTIVE: To describe a method of assessing minor depression and its effects on
      functional status, medical co-morbidity, seasonality, and demographic variables.
      DESIGN: A survey administered to a nonrandom sample of 302 patients. SETTING: A
      university-based family practice outpatient center. PATIENTS: Patients who were
      seen for routine ambulatory care were asked to complete the Inventory to Diagnose
      Depression scale and a modified version of the Dartmouth COOP Functional
      Assessment Charts, including a measure of seasonality. MAIN OUTCOME MEASURES: Six
      categories of functional impairment were examined across two categories of
      depression (major and minor) and the nondepressed. Major depression is defined
      strictly by criteria in the Diagnostic and Statistical Manual of Mental
      Disorders, Revised Third Edition. Minor depression is defined as depressed mood
      or anhedonia and one other of the nine depression symptoms. RESULTS: Forty-seven
      patients (15.6%) had minor depression. Using chi 2 analysis, significant
      differences were found among the three levels of depression for each functional
      status category. Logistic regression analysis showed patients with minor
      depression to have greater odds of more impairment in feelings (odds ratio [OR],
      4.01; 95% confidence interval [CI], 1.75 to 9.19), pain (OR, 2.58; 95% CI, 1.18
      to 5.63), and social activities (OR, 2.48; 95% CI, 1.19 to 5.17) compared with
      the nondepressed patient. The cluster of impairment distinguishing minor from
      major depression differed somewhat, with more impairment in daily activities (OR,
      19.6; 95% CI, 3.45 to 112.00) and feelings (OR, 24.4; 95% CI, 1.78 to 333.00) and
      greater lung disease (OR, 13.7; 95% CI, 2.19 to 80.00) and seasonality (OR, 5.9;
      95% CI, 1.10 to 32.1 for highest seasonality) in patients with major depression.
      CONCLUSIONS: There appears to be significant functional disability associated
      with the presence of minor depression. Seasonality was also present in those with
      minor depression, although it was of greater importance among those with major
      depression. Despite lack of national consensus on the definition of minor
      depression, limitations owing to sampling method, and statistical modeling, there
      is evidence that patients with minor depression reveal a different constellation
      of impairment than do those with major depressive disorder.

PMID- 7804494
TI  - Combination antidepressant therapy in primary care.
AB  - Increasing clinical experience with the selective serotonin reuptake inhibitors
      and tricyclic antidepressants make combination antidepressant therapy at times a
      reasonable alternative to single-agent therapy in primary care patients with
      depression. This article describes three cases that illustrate possible
      rationales for combination antidepressant therapy: reduced side effects,
      synergistic treatment effects, reduced treatment response time, prescriber
      familiarity, and clinical experience. The combination of selective serotonin
      reuptake inhibitors and tricyclic antidepressants may be useful in treating
      patients who experience intolerable side effects or who are resistant to therapy
      with a single antidepressant. Further research should be done to define the role
      of combination antidepressant therapy in the treatment of primary care patients
      with depression.

PMID- 7804495
TI  - Can physicians use family genogram information to identify patients at risk of
      anxiety or depression?
AB  - Advocates of family-oriented care assert that physicians' use of family genograms
      can improve clinical practice, such as in the recognition of patients' emotional
      problems. The purpose of this article is to investigate whether physicians could
      use family genogram information to identify their patients at high risk of the
      two most common mental disorders, anxiety and depression. Physicians' use of
      family genograms to stratify their patients' risk raises two questions about the
      information recorded on the genograms: is family information reliable and valid,
      and is family information associated with anxiety and depression? A review of the
      published epidemiological literature revealed that some basic family information
      recorded on genograms is useful for risk stratification.

PMID- 7804496
TI  - Coffee intake and coronary heart disease.
AB  - We examined the risk of coronary heart disease (CHD) associated with coffee
      intake in 1040 male medical students followed for 28 to 44 years. During the
      follow-up, CHD developed in 111 men. The relative  risks (95% confidence
      interval) associated with drinking 5 cups of coffee/d were 2.94 (1.27, 6.81) for
      baseline, 5.52 (1.31, 23.18) for average, and 1.95 (0.86, 4.40) for most recent
      intake after adjustment for baseline age, serum cholesterol levels, calendar
      time, and the time-dependent covariates number of cigarettes, body mass index,
      and incident hypertension and diabetes. Risks were elevated in both smokers and
      nonsmokers and were stronger for myocardial infarction. Most of the excess risk
      was associated with coffee drinking prior to 1975. The diagnosis of hypertension
      was associated with a subsequent reduction in coffee intake. Negative results in
      some studies may be due to the assessment of coffee intake later in life or to
      differences in methods of coffee preparation between study populations or over
      calendar time.

PMID- 7804497
TI  - Relationship of body fat distribution with cardiovascular risk factors in healthy
      Chinese.
AB  - The relationships between six body girths (shoulder, midarm, waist, hip, thigh,
      and calf) and cardiovascular risk factors (systolic and diastolic blood pressures
      and glucose, triglyceride, lipoprotein cholesterol, and apolipoprotein levels)
      were examined in 407 healthy Chinese urban workers in Taipei, Taiwan who were
      between 40 to 59 years old. Canonical correlation analysis revealed significant
      associations of upper body adiposity (shoulder, midarm, and waist girths) with
      cardiovascular risk factors in all subgroups assessed: men, premenopausal women,
      and postmenopausal women. Waist girth and hip girth were consistent and important
      variables, and weighted in the opposite direction. Waist-hip ratio (WHR) was the
      best descriptor of centralized adiposity. Centralized fat distribution was
      positively associated with blood pressure and glucose, triglyceride, and
      apolipoprotein (apo) B levels, and negatively associated with high-density
      lipoprotein (HDL) cholesterol and apo A-I levels in this population. Body fat
      distribution had an effect independent of body mass index and accounted for some
      of the differences in triglyceride, HDL cholesterol, apo A-I, and apo B
      concentrations among men, premenopausal women, and postmenopausal women. Our
      findings in a Chinese population are similar to data from other studies in
      Western populations, and are consistent with the hypothesis that centralized
      adiposity is related to cardiovascular risk factors independent of general
      obesity.

PMID- 7804498
TI  - Natural menopause and cardiovascular disease risk factors. The Poland and US
      Collaborative Study on Cardiovascular Disease Epidemiology.
AB  - Changes in risk factor levels associated with menopause have been reported in
      many studies in the United States and western Europe, where estrogen replacement
      therapy and surgical menopause are common. We studied risk factor associations in
      Polish women, for whom estrogen replacement therapy and surgical menopause are
      uncommon. The 357 postmenopausal women had higher total cholesterol levels (0.43
      mmol/L) and low-density-lipoprotein cholesterol levels (0.36 mmol/L than did the
      372 premenopausal women of similar ages. Triglycerides, high-density-lipoprotein
      cholesterol, body mass index, and blood pressure did not differ by menopausal
      status. We conclude that natural menopause is associated with higher levels of
      total and low-density-lipoprotein cholesterol levels. Natural menopause is not
      associated with large changes in other risk factors in this sample.

PMID- 7804499
TI  - Tobacco consumption and cognitive impairment in elderly people. A population
      based study.
AB  - We examined the relationship between tobacco consumption and Alzheimer's disease
      (AD), cognitive deficit, and memory performances in elderly community residents
      of southwestern France. Subjects were considered to have a cognitive deficit if
      they scored under 24 on the French version of the Mini-Mental State Examination,
      and poor memory performances if they scored under 8 on the Benton Visual
      Retention Test. Among the 3770 subjects who gave information about their smoking
      habits, only 356 (9.5%) were current smokers, 998 (26.5%) were past smokers, and
      2416 (64%) were never smokers. Current smokers (odds ratio (OR) = 0.52, P <
      0.001) and past smokers (OR = 0.54, P < 0.001) had a lower risk of cognitive
      deficit than did never smokers. However, this significant relationship
      disappeared after adjustment for potential confounding factors such as
      occupational category (OR = 0.91 (not significant) for current smokers and OR =
      0.87 (not significant) for past smokers). Similar results were obtained for the
      risk of AD and of poor memory performances. The apparent protective effect of
      smoking habits on cognitive abilities could be due to a confounding effect of
      occupational category.

PMID- 7804500
TI  - Age at starting smoking and number of cigarettes smoked.
AB  - A cross-sectional analysis of a sample of 3235 males and 2513 females included in
      a structured framework of case-control studies of various neoplasms conducted in
      northern Italy assessed the relationship between age at starting smoking and
      amount of cigarettes smoked per day. Age-standardized proportions of light,
      moderate, and heavy smokers and mean numbers of cigarettes smoked per day
      according to age at starting, together with age- and sex-adjusted odds ratios of
      being a heavy smoker were computed. Age at starting smoking was strongly
      associated with the number of cigarettes smoked per day. This relationship was
      evident in men and women and at younger and elderly ages, although in women the
      mean numbers of cigarettes smoked was lower than in men, and age at starting was
      a stronger predictor of subsequent heavy smoking in people younger than 55 years
      than in the elderly. Among males who had started smoking before age 17, 64%
      smoked less than 25 cigarettes/d and 37% smoked 25 or more cigarettes;
      corresponding proportions were 73% and 27% among those who had started at age 30
      or later. Age-standardized mean number of cigarettes smoked per day by men who
      started before age 17 was 23.5, compared to 20.0 for those who started at age 30
      or later. Corresponding values for women were 16.8 and 10.5. Compared to those
      who started smoking at age 30 or later, the odds ratios of smoking more than 25
      cigarettes/d for those who started before age 17 were 2.2 (95% confidence
      interval (CI), 1.6 to 3.0) for men and 5.4 (95% CI, 3.0 to 9.6) for
      women.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7804501
TI  - Prevalence, incidence, and correlates of syphilis seroreactivity in multiethnic
      San Francisco neighborhoods.
AB  - To examine the extent of infection with syphilis in an inner-city community, we
      determined the prevalence, incidence, and correlates of syphilis seroreactivity
      in a representative sample of unmarried whites, African Americans, and Hispanics
      living in San Francisco during 1988 to 1989 and again 1 year later in 1989 to
      1990. One thousand seven hundred seventy single men and women aged 20 to 44 were
      surveyed in a random household sample drawn from three neighborhoods of varying
      geographic and cultural characteristics. Syphilitic infection was determined by
      testing specimens with the microhemagglutination assay for antibodies to
      Treponema pallidum (MHA-TP). Of blood samples available from 1262 participants
      from the initial survey, 32 (2.5%) were MHA-TP reactive. After adjustment for
      age, a reactive syphilis serology was significantly predicted (P < 0.05) by
      African American race, homosexual activity (men), and less education. In
      homosexually active men, lifetime number of male sex partners and the presence of
      antibody to the human immunodeficiency virus (HIV) significantly predicted
      syphilis seroreactivity (P < 0.01). One year later, of 841 specimens available
      for testing, an additional 13 (1.5%) had become MHA-TP reactive. Eleven (85%) of
      the new cases were in heterosexual men and women. Although San Francisco citywide
      incidence data indicate that syphilis may be decreasing for the city as a whole,
      incidence data on a community level suggests that syphilitic infection is
      increasing in high-risk heterosexual communities. Thus, syphilis prevention
      programs should rely on serologic testing at the community level to plan
      effective intervention strategies.

PMID- 7804502
TI  - Human immunodeficiency virus type 1 antibody status and changes in risk behavior
      among drug users.
AB  - The associations of human immunodeficiency virus type 1 (HIV-1) antibody status
      and recent testing with risk behavior change were examined in a cohort of drug
      users enrolled in a randomized trial of acquired immunodeficiency syndrome (AIDS)
      education programs at a short-term inpatient detoxification facility. Four
      hundred ninety-seven subjects completed baseline interviews, and 402 (81%) of
      them had analyzable follow-up information. Changes in eight ordinal self-reported
      drug and sexual behaviors were assessed using the cumulative logit model for
      repeated ordinal response data. There was only limited evidence for differential
      behavior change by either perceived serostatus or recent testing, which was
      mainly confined to sharing of injection equipment among those who continued to
      inject, and condom use.

PMID- 7804503
TI  - Epidemiologic factors correlated with multiple sexual partners among women
      receiving prenatal care.
AB  - A cross-sectional survey methodology was used to respond to the need of a local
      health department to identify correlates of high-risk behaviors related to human
      immunodeficiency virus (HIV) transmission among pregnant women attending prenatal
      care clinics. This study of 488 maternity patients was conducted at two public
      health clients in Tampa, Florida, in 1991. The prevalence of high-risk behaviors
      was assessed using a self-administered questionnaire. Out of 428 respondents, 25%
      reported having had intercourse with two or more male partners in the past year.
      Following multiple logistic regression analysis, four variables remained
      consistently and significantly associated (P < 0.05) with having two or more
      sexual partners: (1) annual household income of less than $10,000/y (prevalence
      odds ratio (POR) = 4.5; 95% confidence limits (CL): 1.5, 13.1); (2) history of
      prostitution (POR = 8.1; 95% CL: 1.5, 42.1); (3) history of rape or forcible
      intercourse (POR = 2.2; 95% CL: 1.0, 4.6); and (4) an expressed desire for
      confidentiality among women seeking further information about acquired
      immunodeficiency syndrome (AIDS) prevention (POR = 2.1; 95% CL: 1.1, 4.0).
      Assessment of these factors may lead to better direction of HIV education
      programs, as well as identification and counseling of specific individuals at
      high risk for engaging in behaviors that can lead to HIV infection. Short, self
      administered questionnaires provide confidential, rapid, and inexpensive means of
      generating baseline data for further interventions.

PMID- 7804504
TI  - Worldwide patterns and trends in mortality from liver cirrhosis, 1955 to 1990.
AB  - Trends in mortality rates for liver cirrhosis between 1955 and 1990 have been
      analyzed for 38 countries (two from North America, six from Latin America, five
      from Asia, 23 from Europe, and Australia and New Zealand) on the basis of
      official death certification data derived from the World Health Organization
      database. Chile and Mexico had exceedingly high rates (around 60/100,000 males
      and 15/100,000 females in the late 1980s), while in Canada, the United States,
      and Latin American countries that provided data, cirrhosis death rates were
      between 5 and 17/100,000 males and 3 and 5/100,000 females over the same calendar
      period. The pattern of trends was, however, similar in all American countries,
      with some increase between the 1950s and the 1970s, and declines thereafter. A
      similar trend was observed in Japanese males, whose rate was 13.6 in 1990.
      Conversely, cirrhosis mortality declined steadily from 8.0 to 4.6 in Japanese
      females. Appreciable downward trends were observed in Hong Kong and Singapore,
      whereas mortality increased in Thailand. In Europe, in the late 1950s, the
      highest rates were registered in Portugal (33.6/100,000 males and 14.6/100,000
      females), followed by France (31.8/100,000 males and 14.1/100,000 females),
      Austria, Italy, Spain, and Germany. Most of these countries, however, after some
      further rise up to the 1970s, showed reversal of the trends over most recent
      years. Thus, in the late 1980s or early 1990s, only Austria, Italy, and Portugal
      had cirrhosis mortality around 30/100,000 males and 10/100,000 females. Britain,
      Ireland, and Nordic countries started from much lower values (2 to 4/100,000
      males), but showed some, although discontinuous, upward trend.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7804505
TI  - Exposure to ionizing radiation and risk of cutaneous malignant melanoma. Search
      for error and bias.
AB  - In a 1984 case-control study of cutaneous malignant melanoma (CMM) among workers
      at the Lawrence Livermore National Laboratory, Austin and Reynolds found an
      association between reported employment in proximity to ionizing radiation and
      CMM (odds ratio (OR) = 5.4; 95% confidence interval (CI): 1.4, 20.7). But in a
      preliminary study in 1981, they found no association between individual radiation
      dosimetry readings and CMM. We reanalyzed the 1984 Austin-Reynolds case-control
      data to determine whether error or bias explain the inconsistency between
      reported employment in proximity to radiation and individual radiation dosimetry
      readings. Using individual radiation dosimetry readings, we developed an index of
      occupation-specific radiation. This index was associated with case status (OR =
      10.8; 95% CI: 1.4, 85.1). No definitive evidence for influential matched sets,
      confounding, recall bias, or any other sources of bias was identified. These
      results suggest that the odds ratio for reported employment in proximity to
      radiation may be valid.

PMID- 7804506
TI  - Coffee and coronary heart disease. A new problem with old brew?

PMID- 7804507
TI  - Hemodynamic and neural effects of urapidil and prazosin in essential
      hypertensives.
AB  - Assessment of the effects of antihypertensive drugs on sympathetic cardiovascular
      modulation is aimed not only at exploring the neural mechanisms of the
      hypotensive action of different pharmacological compounds but also at evaluating
      the effects of these drugs on neural cardiovascular homeostatic control. This
      paper, after reviewing the effects of different antihypertensive drugs on
      efferent postganglionic muscle sympathetic nerve activity directly assessed in
      man via the microneurographic technique, will report the preliminary results of a
      study we have recently performed in 12 untreated mild essential hypertensives.
      This study was aimed at examining the effects of a single oral administration of
      either the hybrid drug urapidil (30 mg) or the pure alpha-blocker prazosin (2 mg)
      on arterial blood pressure (Finapres technique), heart rate (electrocardiogram)
      and muscle sympathetic nerve activity (microneurography at the peroneal nerve).
      For similar blood pressure reductions, urapidil caused a lesser degree of
      tachycardia in comparison with prazosin (+5.1 +/- 1.2 vs +8.4 +/- 0.8 beats/min,
      p < 0.05) but superimposable increases in muscle sympathetic nerve traffic (+15.4
      +/- 2.8 vs 17.5 +/- 3.5 bursts/min). These results suggest that the two drugs
      induce similar degrees of blood pressure reduction as well as of muscle
      sympathetic activation. Urapidil, however, is accompanied by less tachycardia
      than prazosin, presumably because of a selective drug's action on either
      parasympathetic or sympathetic modulation of heart rate, triggered by the
      stimulation of central 5HT1A-receptors.

PMID- 7804508
TI  - Comparison of the hemodynamic effects of urapidil and flesinoxan in healthy
      volunteers.
AB  - The possible role of peripheral 5HT1A-receptors in the vasodilation caused by
      urapidil was studied by means of venous occlusion plethysmography in the forearm
      vascular bed of healthy volunteers. Urapidil is known to be an alpha 1
      adrenoceptor antagonist and an agonist of 5HT1A-receptors. The hemodynamic
      effects of urapidil were compared with those of flesinoxan, a selective 5HT1A
      receptor agonist virtually devoid of alpha 1-adrenoceptor antagonistic activity,
      and with the selective alpha 1-adrenoceptor antagonist doxazosin, which has no
      affinity for 5HT1A-receptors. Urapidil, as well as doxazosin, caused a dose
      dependent decrease in forearm vascular resistance (FVR), thus reflecting
      vasodilation. Both urapidil and doxazosin were competitive antagonists of the
      vasoconstrictor effect of the selective alpha 1-adrenoceptor agonist methoxamine.
      On a molar base doxazosin proved more potent than urapidil (more than 10-fold).
      Flesinoxan slightly decreased FVR only at high doses. The nitric oxide (NO)
      synthase inhibitor NG-monomethyl-L-arginine acetate (L-NMMA) depressed the
      vasodilatation caused by serotonin and also that by high-dose flesinoxan. The
      serotonin-induced vasodilatation is known to be NO-dependent. From the
      experiments it is concluded that peripheral 5HT1A-receptors cannot play an
      important role in the vasodilator response caused by urapidil, which is
      predominantly the result of postsynaptic alpha 1-adrenoceptor blockade. 5HT1A
      receptors are clearly not involved in the NO-dependent dilatation caused by
      serotonin. During chronic treatment of hypertension with urapidil central but not
      peripheral 5HT1A-receptors may be assumed to play a role.

PMID- 7804509
TI  - Cardiac morphology and function in arterial hypertension. The effects of a new
      multifactorial hypotensive agent: urapidil.
AB  - It has been recognized as increasingly important to determine whether
      antihypertensive agents, while satisfactorily lowering the blood pressure, at the
      same time adversely or positively affect the cardiac hemodynamic profile. On
      theoretical grounds, one would expect that an ideal hypotensive drug should
      decrease blood pressure by decreasing total peripheral resistances, without
      affecting cardiac output, and should normalize left ventricular hypertrophy
      without deteriorating systolic or diastolic left ventricular function. We here
      briefly review the effects of urapidil on these variables in patients under
      chronic treatment investigated in a series of studies employing echocardiography.
      The results of the studies are in fair agreement and indicate a blood pressure
      decrease already after one month of treatment, due to a decrease of peripheral
      resistances, without changes in heart rate. A clear trend towards a reduction of
      cardiac hypertrophy during the treatment is suggested by the significant
      decrements of the indices measured. One study also suggests that right
      ventricular wall thickness may be reduced. Left ventricular dimensions remained
      unchanged in all except one study. Systolic and diastolic function indices were
      also unchanged during the first 6 months of treatment and, in one study,
      improvement was found after 12 months of treatment. Taken together these results
      suggest that urapidil lowers blood pressure favorably, affecting cardiac
      morphology and function.

PMID- 7804510
TI  - Comparison of the effects of urapidil and nitroprusside on hemodynamics and
      myocardial function in hypertension following cardiac surgery.
AB  - Hypertension associated with tachycardia, elevated filling pressures and
      increased systemic vascular resistance occurs in 30-60% of patients recovering
      from coronary artery surgery (1,2). It is usually present when the patients
      arrive from the operating room in the intensive care unit (ICU), or develops in
      the first two hours postoperatively. Traditionally sodium nitroprusside (S) is
      the drug of first choice for the i.v. treatment and prevention of hypertension
      and increased filling pressures developing after coronary artery surgery (CAS).
      Its major disadvantage is reflex tachycardia associated with increased myocardial
      oxygen consumption. Urapidil (U) has both peripheral alpha-1-adrenoreceptor
      blocking activity and a central antihypertensive effect at the level of the 5HT
      1A serotonergic receptor, resulting in enhanced peripheral sympathetic inhibition
      (3,4). Informed consent and institutional approval for the study were obtained.
      When mean arterial blood pressure (MAP) increased above 90 mmHg within the first
      2 hours after CAS, 53 patients were randomly allocated to one of two groups. 25
      patients received U (bolus of 25 mg; initial infusion rate of 15-85
      micrograms/kg/min; maintenance infusion rate of 2-7 micrograms/kg/min) and 28
      patients received S (initial infusion rate of 1-2 micrograms/kg/min; maintenance
      infusion rate of max. 5 micrograms/kg/min). The infusion rate was then adjusted
      to maintain MAP between 80 and 90. Measuring points were: 1. baseline; 2. 30 min
      after starting the infusion; 3. 60 min after starting the infusion; and at 2 hour
      intervals thereafter until the next morning.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7804511
TI  - Urapidil in hypercholesterolemic hypertensive patients.
AB  - The association of arterial hypertension and hyperlipidemia strikingly enhances
      prevalence, incidence and mortality of cardiovascular disease. In the light of
      recent evidence that some antihypertensive drugs with alpha-1 blocking properties
      reduce blood pressure (BP) and total cholesterol (chol), increasing chol content
      in the non-atherogenic high density lipoproteins (HDL-chol), the effects of
      urapidil, a peripheral alpha-1 adrenoceptor antagonist, with a central action
      component on BP and plasma lipids were evaluated in 49 mild, hypertensive
      patients with mild to moderately severe hypercholesterolemia (serum chol 220-320
      mg/dl) for a 6 month period in a double-blind randomized study versus placebo.
      Five out of the 49 patients (3 on urapidil, 2 on placebo) discontinued treatment
      due to adverse side effects. Five patients on placebo did not meet protocol
      requirement of serum triglycerides < 350 mg/dl (3.95 mmol/L) and were only
      included in the BP efficacy assessment. The groups of urapidil and placebo were
      comparable for age (50 +/- 10 vs 49 +/- 7 years), body weight (72 +/- 9 vs 73 +/-
      10 kg), sex (18M, 8F vs 14M, 9F) and mean arterial pressure (119.4 +/- 4 vs 119.7
      +/- 4 mmHg). The actively treated group significantly decrease BP values from
      159/99 +/- 13/2 to 152/90 +/- 23/8 mmHg, whilst no change was observed in the
      placebo group. Between group analysis showed a significant difference at the end
      of treatment (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7804512
TI  - Treatment of hypertension in the elderly with special reference to urapidil.
AB  - During 1991 and 1992 three major intervention trials were published that dealt
      with the value of antihypertensive treatment in the elderly. The three studies
      were the American Systolic Hypertension in the Elderly Program (SHEP), the
      Swedish Trial in Old Patients with Hypertension (STOP-Hypertension) and the
      British Medical Research Council Trial of Treatment of Hypertension in Older
      Adults. (MRC trial.) The three trials all compared active antihypertensive
      treatment, mainly consisting of diuretics or beta-adrenoceptor blocking agents or
      the two in combination, with placebo. Two of the trials were double-blind (SHEP
      and STOP) whereas the MRC trial was single-blind. All three were multicenter and
      prospective, and patients were randomized to either of the treatment modalities.
      One of the trials (SHEP) was specifically designed to evaluate antihypertensive
      treatment in patients with isolated systolic hypertension. The SHEP, STOP and MRC
      trials all showed that treatment of hypertension in the elderly reduces the risk
      of stroke and cardiovascular events. In the STOP-Hypertension trial, which
      included the oldest patients with the most severe hypertension, total mortality
      was reduced by 43%. It could be argued that novel antihypertensive compounds
      offer equal or better results than the ones obtained with beta blockers and/or
      diuretics. Angiotensin converting enzyme inhibitors and calcium antagonists are
      currently being compared with diuretics and beta-blockers in the STOP
      Hypertension-2 study which prospectively evaluates morbidity and mortality in
      hypertensive patients aged 70-84 years.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7804513
TI  - Modification of cardiovascular risk factors during antihypertensive treatment:
      current and new approach trends. The urapidil experience.
AB  - Arterial hypertension is a well known risk factor for atherosclerosis and its
      complications. Lowering of blood pressure significantly reduces the incidence of
      cerebrovascular events and to a minor extent that of ischemic heart disease.
      Interference of antihypertensive drugs on lipoproteins, glucose and electrolytes
      metabolism has been suggested as a hypothesis for the lower than expected
      protection against cardiac events. The new antihypertensive agents such as
      calcium antagonists, angiotensin converting enzyme inhibitors and post-synaptic
      alpha-1 receptor antagonists have proved to be neutral or to have positive effect
      on metabolic disturbances. Urapidil, a multifactorial antihypertensive agent, has
      been shown to significantly lower blood pressure and to have a favorable impact
      on the metabolic profile in adult and elderly hypertensive patients and in
      patients with diabetes mellitus and elevated blood pressure. Although arterial
      hypertension is a risk factor for atherosclerosis, the clinical events at the
      cerebral and coronary levels are secondary to thrombo-embolic complications. On
      the other hand it has been shown that abnormalities in coagulation factor has a
      prognostic value. Therefore, new and old antihypertensive agents should be
      investigated not only for their effects on hypertension, metabolic profile and
      quality of life but also on coagulation, in order to improve the therapeutic
      profile.

PMID- 7804514
TI  - Urapidil compared with diuretics in the treatment of mild-to-moderate essential
      hypertensive patients: effects on glucose metabolism, insulin sensitivity, and
      lipid profile.
AB  - In this study, 14 mild-to-moderate essential hypertensive patients of both sexes
      were studied with regard to the effects of two different treatments, urapidil (60
      to 180 mg/day) and diuretics (chlorthalidone and hydrochlorothiazide-25 to 50
      mg/day) on glucose metabolism, insulin sensitivity and plasma lipid profile.
      Blood pressure was equally reduced by both treatments. However, urapidil
      treatment was accompanied by significant lower plasma levels of cholesterol, HDL
      cholesterol and triglycerides as compared with diuretic treatment. Also, a
      significantly higher insulin sensitivity index, determined by the euglycemic
      insulin clamp technique, was observed during urapidil therapy. Our results
      demonstrated that urapidil is as effective as diuretics in reducing blood
      pressure of essential hypertensive patients, with the potential advantage of a
      favorable profile in regard to the glucose and lipid metabolisms.

PMID- 7804515
TI  - A comparison of the hemodynamic effects of urapidil, prazosin, and clonidine in
      healthy volunteers.
AB  - Urapidil is an antihypertensive agent known to have central 5HT1A agonistic
      properties in addition to alpha-1 blocking effects. To assess the importance of
      these effects, we compared the hemodynamic effects of a single oral dose of
      urapidil (U, 60 mg) with those of prazosin (Pr, 2 mg), clonidine (Cl, 0.15 mg),
      and placebo (Pl), at rest, during orthostatic tilt, and during submaximal graded
      bicycle exercise tests, in a double-blind randomised crossover study in 24
      healthy male volunteers. The variables studied were heart rate, mean blood
      pressure, cardiac index by bioimpedance, systemic vascular resistance index
      (SVRI), and plasma norepinephrine. Baseline values before drug administration
      were identical. At rest, during tilt, and during identical exercise, compared to
      placebo, urapidil and prazosin caused similar decreases in SVRI, with a smaller
      increase in HR after urapidil than after prazosin (p < 0.01), and without any
      difference in BP. Both drugs increased norepinephrine in a similar manner. In
      contrast, clonidine decreased blood pressure (p < 0.01) and norepinephrine (p <
      0.01) with no difference in heart rate or SVRI. In conclusion, at rest, during
      tilt and during exercise, urapidil and prazosin have similar vasodilating
      effects, but the sympathetic stimulation is less and the parasympathetic
      stimulation greater after urapidil than after prazosin, probably indicating a
      centrally acting effect of urapidil. However, the sympathoinhibitory effect of
      urapidil is less marked than that of clonidine.

PMID- 7804516
TI  - The first cardiac electrophysiology examination for added qualifications:
      American Board of Internal Medicine.

PMID- 7804517
TI  - Effects of partial and complete ablation of the slow pathway on fast pathway
      properties in patients with atrioventricular nodal reentrant tachycardia.
AB  - INTRODUCTION: The purpose of this study was to prospectively compare the effects
      of complete and partial ablation of slow pathway function on the fast pathway
      effective refractory period (ERP). METHODS AND RESULTS: The subjects were 20
      patients (mean age 43 +/- 13 years) with atrioventricular nodal reentrant
      tachycardia (AVNRT), no structural heart disease, and easily inducible AVNRT.
      Autonomic blockade was achieved with propranolol (0.2 mg/kg) and atropine (0.04
      mg/kg). After elimination of AVNRT and during autonomic blockade, the presence of
      residual slow pathway function was determined by the presence of a single AV
      nodal echo and/or dual AV nodal physiology. After autonomic blockade and before
      ablation, the mean fast pathway ERP was 319 +/- 44 msec and the mean slow pathway
      ERP was 251 +/- 31 msec. After slow pathway ablation and during autonomic
      blockade, 7 patients had residual slow pathway function and 13 did not. Complete
      loss of slow pathway function was associated with a shortening of the fast
      pathway ERP from 334 +/- 35 msec to 300 +/- 62 msec (P < 0.01), while the fast
      pathway ERP did not change significantly in patients with residual slow pathway
      function (291 +/- 29 msec vs 303 +/- 38 msec, respectively; P = 0.08). A
      shortening of 30 msec or more in the fast pathway ERP was observed in 11 of 13
      patients who did not have residual slow pathway function, compared to 0 of 7
      patients with residual slow pathway function (P < 0.001). CONCLUSION: Shortening
      of the fast pathway ERP after successful ablation of AVNRT is dependent upon
      complete loss of slow pathway function. This observation is consistent with
      electrotonic inhibition of the fast pathway by the slow pathway.

PMID- 7804518
TI  - Recurrence and late block of accessory pathway conduction following
      radiofrequency catheter ablation.
AB  - INTRODUCTION: Many issues regarding the recurrence of accessory pathway
      conduction and the long-term outcome of late block of accessory pathway
      conduction are still unknown or controversial. METHODS AND RESULTS: Data from 217
      patients who underwent an initially successful radiofrequency ablation of
      accessory pathways and 7 patients with late block of accessory pathway conduction
      following an initially unsuccessful ablation were analyzed. During a mean follow
      up of 19 +/- 11 months, accessory pathway conduction resumed in 21 (10%) of 217
      patients following an initially successful ablation and in 6 (86%) of 7 patients
      with late block of accessory pathway conduction (P < 0.01). After initially
      successful ablations, the recurrence rates of accessory pathway conduction at 1,
      3, and 6 months were 5.9%, 7.4%, and 11.3%, respectively. A late
      electrophysiologic study at 6 months uncovered recurrence in only 1 of 124
      asymptomatic patients, but failed to detect the late recurrence in 2 patients in
      whom the accessory pathway conduction resumed after more than 6 months.
      Multivariate analysis revealed that independent predictors for recurrence of
      accessory pathway conduction were concealed accessory pathway, presence of
      transient effect of radiofrequency pulse, and more than 5 pulses required for
      initial cure. Accessory pathway location, length of the tip electrode of the
      ablation catheter, and repeat radiofrequency pulses ("safety pulses") after
      effective pulses did not predict resumption of accessory pathway conduction.
      CONCLUSIONS: After initially successful ablation, the recurrence rates of
      accessory pathway conduction at 1, 3, and 6 months were 5.9%, 7.4%, and 11.3%,
      respectively. Late electrophysiologic testing had little prognostic value in
      asymptomatic patients following successful ablation. Application of "safety
      pulses" did not prevent recurrence. Late block of accessory pathway conduction
      did not predict long-term efficacy.

PMID- 7804520
TI  - QT dispersion: problems of methodology and clinical significance.
AB  - QT dispersion is defined as the difference in QT interval between the different
      leads of the surface 12-lead ECG. This may provide an indirect measure of the
      underlying inhomogeneity of myocardial repolarization, which is believed to be
      important in arrhythmogenesis. Methodology for determining QT dispersion varies
      significantly between studies, and the results of these studies need to be
      interpreted in light of the methodology used. Although QT dispersion is
      developing into an important research tool, as yet it has no established role in
      clinical practice. Once standardization of methodology is achieved a clinical
      role may emerge, particularly in the assessment of patients before and after
      intervention aimed at reduction of arrhythmia risk.

PMID- 7804519
TI  - Resting and action potentials of nonischemic and chronically ischemic human
      ventricular muscle.
AB  - INTRODUCTION: The effect of chronic ischemia on the electrical properties of
      human cardiac tissue is not well understood. METHODS AND RESULTS: Membrane
      potentials were studied using microelectrode techniques in isolated human
      ventricular tissues obtained from nonischemic (n = 17) or chronically ischemic (n
      = 7) myocardium. In normal Tyrode's solution, resting potential (Vr) was lower in
      ischemic (-70.1 +/- 2.12 mV) than in nonischemic muscles (-77.6 +/- 0.93 mV; mean
      +/- SEM; P < 0.05). In high [K]o (> 10 mM) media, Vr was of similar magnitude in
      both types of tissue (in 21.6 mM [K]o, Vr was -53.1 +/- 2.24 mV in nonischemic
      and -49.6 +/- 2.03 mV in ischemic preparations; n = 7 each; P > 0.05). Lowering
      [K]o caused persistent hyperpolarization in nonischemic muscles, but caused
      depolarization in chronically ischemic preparations (in 2.7 mM [K]o, Vr was -84.9
      +/- 2.74 mV and -61.7 +/- 7.72 mV, respectively; n = 7; P < 0.05). Pinacidil (100
      microM) normalized the response of chronically ischemic preparations to [K]o.
      Action potentials (APs) from nonischemic tissues varied in shape and could show
      aberrations. Epinephrine (1.5 microM) and 4-aminopyridine (3 mM) increased the AP
      duration, while butanedione monoxime (20 mM) and tetrodotoxin (1 microM)
      shortened it. In chronically ischemic muscles, the AP was characterized by the
      absence of a plateau and the presence of a slow phase of final repolarization.
      CONCLUSION: The differential effect of low [K]o on the resting membrane potential
      of nonischemic and chronically ischemic tissues suggests a change in the
      properties or the regulation of background K+ channels during chronic ischemia.

PMID- 7804521
TI  - Conduction defects and arrhythmias in Chagas' disease: possible role of gap
      junctions and humoral mechanisms.
AB  - The protozoan parasite Trypanosoma cruzi causes Chagas' disease, a major cause of
      cardiac dysfunction in Latin Americans. Chagas' disease exhibits both acute and
      chronic phases, and each may be characterized by cardiac conduction disturbances.
      In acutely infected cultures of rodent heart cells, synchronized spontaneous
      beating becomes less regular, and coupling between cells is reduced. The basis of
      this decreased conduction is apparently in localization of the gap junction
      protein (Cx43) inside infected cells. Although total Cx43 is normal in infected
      cells, little is recognizable at appositional membranes. Electrophysiological
      properties are also altered by this infection. Action potentials are shortened,
      resting Ca2+ levels are elevated, and response to alpha-adrenergic agonists was
      altered, compared to controls. Humoral factors may contribute to the conduction
      defects in chronic Chagas' disease. Sera from chronically infected rabbits
      produced ECG abnormalities in Langendorff-perfused rabbit hearts. These findings
      indicate that chagasic infection may modify ion channel function in the heart,
      and we suggest that these changes may be manifested in the conduction
      disturbances that characterize this disease.

PMID- 7804522
TI  - Bridging the gap between basic and clinical electrophysiology: what can be
      learned from monophasic action potential recordings?
AB  - With rapid advances occurring in both basic and clinical electrophysiology, the
      gap between the two disciplines appears to be widening rather than narrowing. In
      most instances, we cannot apply the knowledge derived from cellular studies
      directly to clinical practice. Monophasic action potential (MAP) recording by
      contact electrode technique allows us to measure basic electrophysiological
      phenomena in the human heart and thus provides an important bridge between basic
      and clinical electrophysiology. MAP recordings produce the time course of
      cellular repolarization during cycle length changes and antiarrhythmic drug
      administration, lending insights into use dependency and reverse use dependency
      of antiarrhythmic drug effects in the clinical electrophysiology laboratory. The
      ability to deliver electrical stimuli at the MAP recording site further allows
      one to investigate drug-induced postrepolarization refractoriness. MAP recordings
      provide precise local activation times, important for mapping of abnormal
      ventricular activation, and detect areas of abnormal repolarization due to
      ischemia or scarring. MAP recordings are uniquely suited to detect early and
      delayed afterdepolarizations in the human heart, thereby helping to unravel the
      arrhythmia mechanisms in the long QT syndrome. By embedding the MAP electrode in
      a radiofrequency electrode, arrhythmogenic foci may be both detected and ablated.
      In many instances, MAP recordings are more accurate than ECG tracings in defining
      and distinguishing ventricular fibrillation and ventricular tachycardia. This can
      be of clinical importance during testing of the implantable
      cardioverter/defibrillator. An area of growing interest is stretch-activated
      arrhythmias. Here, MAP recordings are of particular value because no other method
      is available to record mechanically induced electrophysiological changes in the
      vigorously beating heart. It can be expected that MAP recordings will, in the
      future, provide this important bridge between "cell and bedside" also in atrial
      tachyarrhythmias, such as in atrial fibrillation and flutter.

PMID- 7804523
TI  - Ten-year results of the randomized control trials of coronary artery bypass graft
      surgery: tabular data compiled by the collaborative effort of the original trial
      investigators. Part 2 of 2.
AB  - This metaanalysis has some important general implications for conducting studies
      to evaluate other treatments as well as for patient management. To avoid missing
      clinically important differences (eg, 15-20% differences in mortality at 5 years)
      between the methods of revascularization, study populations should be several
      times larger than those in our metaanalysis, should include a high proportion of
      the types of patients for whom surgery is known to be superior to medical
      therapy, and should be complemented by a systematic overview. We recommend that
      researchers running large randomized trials consider prospective collaboration
      with researchers from other trials with a common protocol.

PMID- 7804524
TI  - Ten-year results of the randomized control trials of coronary artery bypass graft
      surgery: tabular data compiled by the collaborative effort of the original trial
      investigators. Part 1 of 2.
AB  - OBJECTIVE: To make available 10-year mortality data compiled and analyzed on
      patients with stable coronary heart disease (angina not severe enough to
      necessitate surgery) from all studies in which patients were randomized to
      initial coronary artery bypass graft (CABG) surgery or initial medical treatment
      and to determine whether the effects are influenced by the extent of coronary
      artery disease and degree of left-ventricular function. Data and analyses are
      presented in tabular form; text is published simultaneously in Lancet. METHODS:
      We collected individual patient data using standardized forms and, whenever
      possible, uniform definitions. We used Mantel-Haentel methods to combine data.
      Restricted means analyses were applied to quantify the extension in survival, and
      logistic regression analyses were applied to assess whether any baseline
      covariate affected the treatment differences. RESULTS: Of 2,649 patients, 1,324
      were assigned to receive CABG surgery and 1,325 to the medical group. Mean age
      was 50.8 years; 98.8% were men. 93.7% of the CABG group underwent surgery. 25% of
      the medical group had undergone surgery at 5 years, 33% at 7 years, and 41% at 10
      years. Initial CABG surgery reduced mortality significantly at 5 years (10.2% vs
      15.8%; OR = 0.61; P < 0.001), 7 years (15.8% vs 21.7%; OR = 0.68; P < 0.001), and
      10 years (26.4% vs 30.5%; OR = 0.83; P < 0.03). Risk reductions were most
      pronounced in patients with left-main disease compared to those with 3- or 1-2
      vessel disease (at 5 years OR = 0.32, 0.58, and 0.77, respectively). CONCLUSIONS:
      Initial CABG surgery compared to initial medical management reduces mortality,
      especially in high- and medium-risk patients.

PMID- 7804525
TI  - In vivo treatment with monoclonal antibodies directed against CD4 and CD8
      antigens in miniature swine.
AB  - Two monoclonal antibodies (mAb) with specificities for mature T-cell subsets in
      miniature swine have been characterized previously. Antibody 74-12-4 recognizes
      the porcine CD4 accessory molecule and 76-2-11 is specific for the CD8 molecule.
      We have now examined the effects of in vivo administration of 74-12-4 and 76-2-11
      on several parameters of transplantation immunity. No prolongation of class I
      disparate skin or kidney graft survival was observed in animals treated with
      either mAb alone or with a combination of both. In addition, in vivo treatment
      with these mAbs, in combination with subtherapeutic total body irradiation,
      failed to permit engraftment of allogenic bone marrow. These therapeutic failures
      were thought likely to be a consequence of the fact that 74-12-4 coats, but does
      not deplete, CD4 cells in vivo. Because there are numerous anti-human mAbs that
      likewise fail to deplete in vivo, we have used 74-12-4 as a prototype to further
      manipulations aimed at achieving depletion. We attempted to eliminate 74-12-4
      coated cells in two animals by subsequent administration of a hyperimmune pig
      anti-mouse Ig serum. In both such treated animals, administration of this serum
      produced surprisingly rapid clearance of 74-12-4 from the circulation and caused
      uncoating of CD4 cells, but no significant cell elimination was detected by flow
      cytometry. We have also prepared an anti-porcine-CD4 immunotoxin by conjugating
      74-12-4 to the ribosome inhibitory plant toxin, pokeweed antiviral protein. This
      immunotoxin led to significant but not complete CD4 cell depletion from the
      peripheral blood in four of four treated animals. Further manipulations and
      possibly development of new anti-porcine CD4 mAbs may therefore be required to
      achieve complete depletion and successful mAb-mediated modification of
      transplantation responses.

PMID- 7804526
TI  - Delivery of cytokines by liposomes. II. Interleukin-2 encapsulated in long
      circulating sterically stabilized liposomes: immunomodulatory and anti-tumor
      activity in mice.
AB  - We have recently demonstrated that recombinant human interleukin-2 (IL-2) can be
      successfully encapsulated in small (mean size, 65 nm), unilamellar, long
      circulating, sterically stabilized liposomes (SSL, also known as Stealth
      liposomes). The present study was undertaken to assess in mice the
      immunomodulatory and anti-tumor effects of SSL-IL-2 in comparison with soluble,
      unmodified IL-2 and pegilated IL-2 (PEG-IL-2). The main findings were as follows:
      (a) SSL-IL-2 was significantly more effective than IL-2 in increasing leukocyte
      number in the blood and spleen (p < 0.05) and triggering spleen lymphokine
      activated killer cell activity (p < 0.01; t test). (b) In mice with advanced
      metastatic carcinoma previously treated with chemotherapy (cyclophosphamide), the
      survival was two to six times greater following administration of SSL-IL-2 as
      compared with IL-2 (p < 0.05; log-rank test). Moreover, successful treatment with
      SSL-IL-2 required lower cumulative doses (1.25 x 10(5) vs. 2.5 x 10(5) CU) and
      fewer (two versus five) administrations. (c) PEG-IL-2 was a more potent
      immunostimulator than SSL-IL-2 in normal mice and as effective therapeutically as
      SSL-IL-2 in tumor-bearing mice. The former agent, however, often caused marked
      toxicity (up to 40% mortality in some experiments), including severe
      thrombocytopenia. These findings suggest that SSL-IL-2 is an immunopotentiating
      agent superior to IL-2 in both normal mice and in tumor-bearing mice pretreated
      with chemotherapy.

PMID- 7804527
TI  - Phase I study of tumor necrosis factor-alpha and actinomycin D in pediatric
      patients with cancer: a Children's Cancer Group study.
AB  - In preclinical studies, synergy was observed between tumor necrosis factor-alpha
      (TNF-alpha) and agents that interact with DNA topoisomerase II, such as
      actinomycin D (Act D). Based upon this, a Phase I study was conducted in
      pediatric patients utilizing an escalating dose of recombinant TNF (rTNF) in
      combination with a fixed dose of Act D. Act D (15 micrograms/kg/day) was
      administered daily by intravenous push immediately followed by intravenous rTNF
      daily for 5 consecutive days. Thirty-three patients with refractory malignancies
      were entered in the study, of whom 28 patients could be evaluated for toxicity.
      Malignancies included sarcomas (16), Wilms' tumor (6), leukemias (3), and others
      (3). The starting dose for rTNF was 40 micrograms/m2/day x 5 and was escalated in
      subsequent patient groups until nonhematopoietic, dose-limiting toxicity
      occurred. At 240 micrograms/m2/day of rTNF, three of six patients experienced
      grade 4 toxicity consisting of hypotension, hemorrhagic gastritis, and renal and
      liver biochemical abnormalities. Evidence of antitumor response was observed in
      two patients: one with metastatic Ewing's sarcoma and one with Wilms' tumor. We
      conclude that the maximum tolerated dose of rTNF when combined with Act D is
      between 200 and 220 micrograms/m2/day x 5 for pediatric patients.

PMID- 7804529
TI  - 5th conference on radioimmunodetection and radioimmunotherapy of cancer. October
      6-8, 1994, Princeton, New Jersey. Program and abstracts.

PMID- 7804528
TI  - Phase Ib trial of granulocyte-macrophage colony-stimulating factor combined with
      murine monoclonal antibody R24 in patients with metastatic melanoma.
AB  - R24, a murine monoclonal antibody, has been shown to mediate complement- and
      antibody-dependent cellular cytotoxicity (ADCC) of melanoma tumor targets. We
      conducted a Phase Ib clinical trial using granulocyte-macrophage colony
      stimulating factor (GM-CSF) and R24 in 20 patients with metastatic melanoma. The
      purpose of this study was to test the hypothesis that treatment with GM-CSF could
      up-regulate monocyte and granulocyte ADCC and that the combination of GM-CSF plus
      R24, which mediates ADCC, would lead to enhanced anti-tumor activity in patients
      with melanoma. GM-CSF was administered by subcutaneous injection daily for 21
      days at a dose of 150 micrograms/m2/day. R24 was administered by continuous
      intravenous infusion on days 8-15 at three dose levels: 0, 10, and 50 mg/m2/day.
      All 20 patients received one cycle of treatment only. Immune parameters measured
      were monocyte and granulocyte direct cytotoxicity and ADCC. All patients were
      evaluable for toxicity. Fifteen patients were evaluable for immune response.
      Treatment with GM-CSF alone was well tolerated. Toxicity from the combination of
      GM-CSF plus R24 included diffuse urticaria, nausea and vomiting, hypertension,
      and hypotension. Hypotension was the dose-limiting toxicity. Two patients on the
      50-mg/m2/day dose level of R24 achieved a partial response lasting 2+ and 5+
      months. Treatment with GM-CSF led to a statistically significant enhancement of
      monocyte and granulocyte direct cytotoxicity and ADCC. The maximally tolerated
      dose of R24 given at this schedule combined with GM-CSF is < 50 mg/m2/day. We
      conclude that GM-CSF given by subcutaneous injection at 150 micrograms/m2 x 21
      days can enhance effector cell ADCC and direct cytotoxicity and that the
      combination of GM-CSF and R24 can be therapeutic.

PMID- 7804530
TI  - Enhancement of immune reactivity in the lymph nodes draining a murine melanoma
      engineered to elaborate interleukin-4.
AB  - The adoptive transfer of immune T cells has been demonstrated to mediate
      regression of established tumors in animals, with encouraging results in human
      clinical trials. In animal studies, lymph nodes (LN) draining a progressively
      growing immunogenic tumor contain tumor-sensitized but functionally deficient T
      cells. These "preeffector" cells can be activated in vitro by sequential
      stimulation with anti-CD3 and interleukin (IL)-2 to differentiate into mature
      effector cells capable of mediating the regression of disseminated tumor.
      However, the preeffector cell response is weak during the growth of poorly
      immunogenic tumors such as the B16-BL6 melanoma. In this study, a clone of B16
      BL6, A9, was transfected with the cDNA encoding for murine IL-4, in an attempt to
      enhance tumor immunogenicity. IL-4 secreting clones grew significantly slower
      than controls after intradermal (i.d.) inoculation, but all animals eventually
      succumbed to the progressive tumor. The ability of IL-4-secreting tumor cells to
      stimulate a preeffector cell response was then investigated. LN draining the IL-4
      secreting tumors for 10 days were activated by the anti-CD3/IL-2 method. The
      resulting lymphocytes were adoptively transferred into animals bearing 3-day
      established parental pulmonary metastases. The transfer of cells derived from
      sensitization with the IL-4-secreting tumors was capable of significantly
      reducing the numbers of pulmonary metastases more effectively than cells
      sensitized to the parental tumor. Thus, genetic modification of tumor cells to
      secrete IL-4 can stimulate an increase in the preeffector cell response in the
      tumor-draining LN, suggesting an enhancement in T-cell-mediated immune function
      against the parental tumor.

PMID- 7804532
TI  - Stimulation of cytolytic activity by interleukin-10.
AB  - Interleukin-10 (IL-10), originally identified as an inhibitor of cytokine and
      monokine synthesis [e.g., IL-2, interferon-gamma (IFN-gamma), and tumor necrosis
      factor (TNF-alpha)], modulates a wide range of immunologic activities. In the
      present study we have examined the induction of non-major histocompatibility
      complex-restricted cytolytic activity in human peripheral blood mononuclear cells
      (PBMCs). PBMCs incubated with human IL-10 for 3 days were used as effector cells
      in cytotoxicity (i.e., 51Cr release) assays against a panel of human tumor cells.
      In a concentration-dependent manner. IL-10 stimulated or potentiated lytic
      activity against several human tumor cell lines. Induction of cytolytic
      activities by IL-10 was neutralized by anti-IL-10 monoclonal antibodies but not
      by antibodies against IFN-gamma or TNF-alpha. Co-incubation of PB-MCs with IL-10
      and IL-2 or IL-10 and IFN-alpha augmented cytolytic activity, in particular at
      lower effector-to-target ratios. IL-2-induced release of TNF-alpha was
      dramatically reduced by IL-10; however, the expression of lymphokine-activated
      killer (LAK) activity was not affected. PBMCs preactivated with IL-10 before
      addition of IL-2 displayed higher levels of LAK activity. Inhibition of IL-2
      driven LAK activity by IL-4 is alleviated by IL-10. Finally, IL-10 is not
      affected by inhibitors of IL-2, such as IL-4 and transforming growth factor-beta.
      Potential application of IL-10 to anti-tumor therapies is discussed.

PMID- 7804531
TI  - T-cell receptor repertoire in tumor-infiltrating lymphocytes. Analysis of
      melanoma-specific long-term lines.
AB  - Cytotoxic T-lymphocytes (CTLs) can be isolated from human melanoma biopsies that
      specifically lyse autologous melanoma in vitro and can be effective therapeutic
      agents for patients with advanced disease. Recent evidence indicates that HLA-A2
      restricted, melanoma-specific tumor-infiltrating lymphocytes (TILs) recognize
      melanomas obtained from different HLA-A2+ patients, suggesting the presence of
      one or more common melanoma antigens. Furthermore, T-cell receptor (TCR)
      repertoire analysis by other groups of TILs from fresh melanoma biopsies suggests
      that there is limited TCR V gene usage in TILs. One serious limitation in
      analyzing the TCR repertoire in fresh tumors has been the inability to correlate
      TCR usage with immune function. Therefore, the TCR repertoire was determined in
      long-term TIL cultures that specifically lysed autologous melanoma in vitro and
      in many cases mediated in vivo regression of metastatic cancer in patients with
      advanced disease. The TCR repertoire in cultured melanoma-specific TILs was
      diverse, with each TIL containing an average of 9.5 +/- 5.7 of the 23 V alpha and
      11.2 +/- 5.9 of the 23 V beta subfamilies. Despite the large diversity observed,
      several V alpha and V beta genes (V alpha 1, V alpha 2, V alpha 22, V beta 13, V
      beta 14, and V beta 18) are very commonly found in melanoma-specific TILs. No
      statistically significant associations were observed between the presence of a
      TCR V gene subfamily in TILs and clinical response, HLA haplotype, or age of the
      culture. Even though the results in this study suggest that certain TCR V gene
      segments may be involved in immune responses to human melanoma, we were unable to
      demonstrate functionally that a particular T-cell clonotype recognizes melanoma
      tumor-associated antigens. Only the analysis of melanoma-specific CTL clones can
      determine which clonotypes are important in lysis of human melanoma.

PMID- 7804533
TI  - [Rotation: a choice of possibilities].

PMID- 7804534
TI  - [Education by exchange. Stakes of a pedagogical project].

PMID- 7804535
TI  - [Role of practice in the construction of professional identity].

PMID- 7804537
TI  - [Teaching the student's project].

PMID- 7804536
TI  - [Exchange in the formation of nurses groups in the psychiatric sector. Looking
      for meaning].

PMID- 7804538
TI  - [Protocol of admission and assignment of nursing students in clinical practice].

PMID- 7804539
TI  - [A pedagogical contract].

PMID- 7804540
TI  - [New education by rotation].

PMID- 7804541
TI  - [The course book: a tool for teaching continuity].

PMID- 7804542
TI  - [Students and nursing policies].

PMID- 7804543
TI  - [Interest of nurses in the participation in establishment policies].

PMID- 7804544
TI  - [Clinical decisions in nursing care].

PMID- 7804545
TI  - [The share of women in health care].

PMID- 7804547
TI  - [Nursing of psychosomatic disorders].

PMID- 7804546
TI  - [The Commission on Nursing Care. The right to expression of nursing students].

PMID- 7804548
TI  - [Compliance: a task for the nurses].

PMID- 7804549
TI  - [Overcoming anxiety].

PMID- 7804550
TI  - [Working with families. Through our curiosity we may find family "credos"].

PMID- 7804551
TI  - [Nursing diagnoses. Preconditions, development and limitations].

PMID- 7804552
TI  - [A changing profession. The future of nursing service and of nursing
      administration].

PMID- 7804553
TI  - [A new start towards qualification. Interview with the teachers of the Essen
      educational center on their new educational concept].

PMID- 7804555
TI  - [More legal questions--more articles on practice. Results of the reader query by
      "Pflege aktuell"].

PMID- 7804554
TI  - [Quality and professionalism in nursing. Breaking a lance for the professional
      nursing seminar].

PMID- 7804556
TI  - [Freedom-restricting measures].

PMID- 7804557
TI  - [Nursing worldwide. The current situation of the nursing professions].

PMID- 7804558
TI  - [Amnesty International: we protest].

PMID- 7804560
TI  - [Nursing research for nursing practice?. Interview by Eva-Maria Krampe].

PMID- 7804559
TI  - [News from Finland].

PMID- 7804561
TI  - The concept of cure in cancer care.
AB  - The concept of cure is often used in health care practices without thought to the
      social, cultural and psychological implications of its meaning. Frequently
      measured in terms of years of disease-free survival, this measure is inadequate
      in evaluating treatment. Iatrogenic toxicities and illness implications may
      linger for many months or years after a person experiences cancer. The
      subcultural perspectives of cure for clinicians may be very different.
      Historically, the clinician's concept of cure has been the focus and reported
      outcome of cancer treatment and research. A more dynamic view is encouraged in
      exploring this concept in relation to the outcomes of nursing practice.

PMID- 7804562
TI  - Cancer therapy-induced emesis: the nurse's perspective.
AB  - There have been significant improvements in the diagnosis and treatment of
      malignant tumours. However, recent advances in cytostatic therapy are associated
      with several adverse side-effects which can impair the patient's well-being and
      may result in refusal or delay of treatment. Nausea and vomiting are perceived to
      be the most unpleasant of these side-effects. This paper addresses some of the
      issues involved in the improvement of these two distressing symptoms.

PMID- 7804563
TI  - People with cancer have the right to expect the best possible treatment and care.
AB  - Planning care for the patient who has cancer in his own home is at the same time
      similar, yet profoundly different from planning care for the patient in hospital.
      The similarity arises out of the diagnosis and prognosis. The difference lies in
      the intermittent nature of home nursing as opposed to the continuity of hospital
      care. Although professional care is enlisted, the bulk of the care will be given
      by nonprofessionals, such as the patient's family and friends. Hospital doctors
      do not identify the same sort of goals for terminally ill patients as their
      hospice and their nursing colleagues in general hospitals (Lunt, 1985). They
      rarely include the needs of relatives in their plans and have a much smaller
      range of goals. Therefore, they need to be encouraged to participate with other
      team members and to listen to the views of their multi-disciplinary colleagues.
      Everyone who is responsible for discharging a patient into the community must be
      aware of the appropriate services that can be provided.

PMID- 7804564
TI  - The Maastricht Treaty: setting a health care agenda for Europe.
AB  - This paper is intended to promote awareness among the European cancer nursing
      community of recent developments in the European Union's views on health. The
      paper outlines the background leading to the Treaty on European Union (Maastricht
      Treaty). The main features of the Treaty are identified and Article 129 of the
      Treaty on the provisions for public health and prevention of disease is
      discussed. The implications of the Treaty for health care in general and cancer
      care in particular are addressed.

PMID- 7804565
TI  - Some parameters of lipid metabolism in women 6 years after surgery on account of
      uterine leiomyoma.
AB  - The examinations were carried out in 44 women (age between 40 and 60 years) six
      years after surgery on account of a uterine leiomyoma. The total cholesterol (TC)
      level, HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), triglycerides (TG) and
      17 beta-estradiol (E2) as well as the values of the atherogenic coefficient HDL
      C/TC- and HDL-C/LDL-C were assessed. The subjects were divided into 3 age groups
      as well as groups with regard to the extent of surgery. In younger women with
      partial oophorectomy no changes of the lipid metabolism were found. In older
      women, however, with hysterectomy and oophorectomy, the risk of atherosclerosis
      reached the threshold of compensatory abilities and was marked by a decrease of
      mean values of HDL-C/LDL-C (p < 0.05), with an increase of HDL-C/TC- (p < 0.001).

PMID- 7804566
TI  - [Comparison of the results of conventional ultrasonography and color doppler
      analysis in the evaluation of the nature of adnexal tumors. I. Conventional
      vaginal ultrasound].
AB  - The author evaluates the results of ultrasonographic examination of adnex tumours
      in 317 patients, in correlation with the histological postoperative findings. US
      evaluation was focused on the quality and quantity of tumour echogenity, tumour
      size, its boundaries, possible presence of free fluid (ascites) in the abdominal
      cavity. The author discusses also factors influencing the US finding. It was
      revealed that the different criteria of conventional vaginal sonography only
      indicate the "direction of the nature of the tumour". The value of US criteria
      increases if several positive criteria are present simultaneously.

PMID- 7804567
TI  - [Psychosexual reactions in women after treatment of breast carcinoma].
AB  - Within the framework of a more extensive investigation of a group of women after
      treatment of a malignant breast tumour the authors paid also attention to their
      psychoesexual reactions. 119 probands were divided with regard to the type of
      their answers into three sub-groups: A - sthenic reaction (n = 35, i.e. 29.4% of
      the group), B - asthenic reaction (n = 55, 46.2%) and C - escape reply (n = 29,
      24.4% of the group). The above sub-groups were compared, using the final score of
      four questionnaires (Heterosexual development of woman, Sexual activity of woman,
      Sexual function of woman and N5 questionnaire of neuroticism). The sub-group of
      women with the asthenic type of reaction was, as compared with the other two sub
      groups, much more neurotic which in the authors' opinion indicates the need of
      professional psychotherapeutic care along with basic oncological treatment. As
      expected, in the examined group as a whole poor values were recorded in the
      questionnaires on sexual activity and sexual function. The values recorded in the
      three sub-groups with different psychosexual reaction, however, did not differ
      significantly.

PMID- 7804569
TI  - [Prevention, diagnosis and treatment of thromboembolic complications and
      disseminated intravascular coagulation in obstetrics].

PMID- 7804568
TI  - [Monitoring of malignant gynecologic tumors using the immune response to lactate
      dehydrogenase virus antigens].
AB  - The cell mediated immunity was examined by the leukocyte adherence inhibition
      (LAI) test in 21 patients with CIN III and 146 patients with invasive
      gynaecologic malignancies before treatment and at 3-month intervals. Our own LDV
      antigen and organ specific antigens were used. The test was highly specific
      (95.1%) in comparison with a control group of healthy blood donors. The
      sensitivity of the test was lower (64.7-86.8%). There was no correlation with the
      development of disease (remission or relapse). The test in a two-year
      investigation does not seem suitable for monitoring of disease. Depending the
      nature of LDV infection, only a longer investigation extending over more years
      would enable further conclusions.

PMID- 7804570
TI  - [The cesarean section scar and subsequent childbirth. I. Evaluation of the scar
      and its consequences].

PMID- 7804571
TI  - [Results of a conservative approach in premature loss of amniotic fluid].

PMID- 7804572
TI  - [Therapy of hirsutism with flutamide, a new non-steroidal antiandrogen].

PMID- 7804573
TI  - [Antiphospholipid antibodies, the antiphospholipid syndrome and pregnancy].

PMID- 7804574
TI  - [Occult ovarian failure and idiopathic sterility].

PMID- 7804575
TI  - Mechanism of closed chest cardiopulmonary resuscitation investigated by
      transoesophageal echocardiography.
AB  - Transoesophageal echocardiography (TOE) was performed during closed chest
      cardiopulmonary resuscitation (CPR) in 18 subjects in cardiac arrest. Compression
      of all four cardiac chambers resulted in forward flow in the pulmonary and
      systemic circulations, retrograde pulmonary vein flow and incomplete mitral valve
      closure. Antegrade pulmonary vein flow and left ventricular filling occurred
      exclusively during the relaxation phase. These findings support the cardiac pump
      theory of CPR and are incompatible with the thoracic pump mechanism. TOE merits
      further investigation as a device to monitor and guide resuscitation efforts
      during CPR.

PMID- 7804576
TI  - Management of minor head injuries in the accident and emergency department: the
      effect of an observation ward.
AB  - The management of 483 patients presenting with minor head injury to the accident
      and emergency (A&E) departments of two Scottish hospitals was studied
      prospectively. Such patients comprised 5.7 and 3.9% of the total attendances to
      each department. Of the 277 patients assessed in the former department, 83 (30%)
      fulfilled at least one of the currently accepted criteria for recommending
      admission to hospital and 49 (17.7%) patients were actually admitted. Patients in
      whom head injury was not the principal reason for admission were excluded from
      the study. In the same time period the second department dealt with 206 patients
      with minor head injury, 49 (24%) of whom had criteria for admission. However,
      significantly fewer, 10 (4.9%) patients, were actually admitted. The major
      relevant factor when comparing the two departments was the existence in the
      former of an observation ward. These results support the view that easy access to
      hospital beds is a major determinant of management in patients presenting with
      minor head injury to the A&E department and may be more influential than clinical
      findings.

PMID- 7804577
TI  - Analysis of emergency department interpretation of electrocardiograms.
AB  - The objective of the study was to determine the concordance of emergency
      physicians' and cardiologists' interpretations of emergency department (ED)
      electrocardiograms (ECG), to evaluate the impact of ECG misinterpretation on
      patient management, and to determine error rates as a function of the level of
      physician training and the specific ECG diagnoses. ECG interpretations were
      registered prospectively using a programmed-response data sheet. A second blinded
      interpretation by a staff cardiologist was assumed to be correct. Only ECG
      discrepancies with potential or probable clinical importance were considered as
      errors. The ED management of patients with ECG misinterpretations was reviewed by
      the investigators. The study was performed at an urban university hospital using
      300 consecutive ED ECGs. The analysis found 154 errors of interpretation of which
      nine had probable clinical significance, and 56 had indeterminant significance.
      The concordance was weak at 0.69 (Kappa = 0.32, weighted Kappa = 0.30) with a
      significant discordance (McNemar Chi 2:P < 0.05). Error rates did not differ
      significantly between the diverse categories of physicians. In two cases,
      interpretation errors impacted patient management decisions but not patient
      outcomes. The most frequent errors involved repolarization abnormalities,
      ventricular hypertrophy and hemi-blocks. While discordance was significant,
      errors in ECG interpretation rarely impacted patient management. Prospective
      evaluation of ECG interpretation may be a useful means of gauging physician
      skills. It can also serve to focus educational activities on problem areas in
      electrocardiography.

PMID- 7804579
TI  - An audit of dermatology in a paediatric accident and emergency department.
AB  - Two studies were undertaken of patients with dermatological disorders who
      attended the Accident and Emergency (A&E) Department of the Royal Belfast
      Hospital for Sick Children during 1990-1991. The aims were to review diagnostic
      accuracy and assess the benefits of an open-access consultant dermatology clinic.
      A retrospective survey of 14,340 new attendances at the A&E department over a 7
      month period found that 540 of these (4%) had a primary dermatological disorder.
      In 26% no diagnosis had been made although only 10% were referred for a
      specialist opinion. A 2-month prospective study of patients who attended the
      department and were referred to a consultant dermatology open-access clinic
      revealed overall diagnostic accuracy of 66% (+/- 2 SEM). Individual rates of
      diagnostic concordance between junior doctor and consultant were 59% for skin
      infections and 77% for papulosquamous disorders. The open-access clinic allowed
      prompt referral for correct diagnosis and initiation of appropriate management.

PMID- 7804580
TI  - Cardiopulmonary resuscitation. Paper 1: A survey of undergraduate training in UK
      medical schools.
AB  - This paper presents the results of a UK national survey of Basic Life Support
      (BLS) and Advanced Cardiac Life Support (ACLS) training for undergraduate medical
      students. In all responding medical schools, undergraduates are taught BLS at
      least once during their course but the assessment and refresher aspects of BLS
      training are not uniformly covered. There are inconsistencies in ACLS teaching,
      with some schools providing formal courses, some teaching specific techniques and
      others providing no ACLS teaching. Most interestingly, of those completing the
      questionnaire, only 52% considered present undergraduate training adequate to
      enable junior house officers to provide an effective resuscitation service. We
      recommend that all aspects of BLS and ACLS training for medical undergraduates be
      improved and standardized throughout the UK.

PMID- 7804578
TI  - AB or ABC: pre-hospital fluid management in major trauma.
AB  - Pre-hospital trauma care in the United Kingdom is a neglected field with little
      consideration being given to this phase. Of the 14,500 annual fatalities from
      road traffic accidents in this country, 60% die before reaching hospital and it
      has been estimated that one-third of these fatalities are due to hypovolaemia.
      The pre-hospital fluid resuscitation of trauma patients is a controversial area
      and although it would seem sensible to commence intravenous (i.v.) fluids at the
      roadside, several large studies have failed to show any benefit from this
      intervention. By delaying departure to hospital, initiation of i.v. fluid
      replacement may actually worsen outcome. This paper reviews recent studies and
      discusses current thought on pre-hospital fluid replacement in major trauma.

PMID- 7804581
TI  - Cardiopulmonary resuscitation. Paper 2: A survey of basic life support training
      for medical students.
AB  - This paper presents the results of a survey of Basic Life Support (BLS) training,
      based on experience gained by undergraduate medical students who had just
      completed their first clinical year (third year) at the University of Glasgow.
      Data were collected on the amount and quality of BLS training received, along
      with students' own perceptions of their confidence in providing BLS in a cardiac
      arrest resuscitation attempt. The results made interesting, but not surprising,
      reading with only 15% of students appearing to have been adequately taught BLS at
      any point during their third year. Students want more training and 98% see
      resuscitation as an important topic in the curriculum. Self-perceived confidence
      in performing BLS in an acute resuscitation situation is low. With no evidence to
      suggest that the situation is any different elsewhere in the UK, it is
      recommended that undergraduate resuscitation training is improved to reflect the
      importance that medical students attach to it.

PMID- 7804582
TI  - Acute bacterial diarrhoea in the emergency room: therapeutic implications of
      stool culture results.
AB  - Empiric treatment with ciprofloxacin and norfloxacin has been recommended
      recently for patients with acute diarrhoeal disease. In a retrospective 6-month
      study period the results of stool cultures from 209 patients with acute diarrhoea
      admitted to the emergency room were analysed. Seventy-eight cultures (37%) were
      positive for one or more bacteria. Shigella was the most commonly isolated
      pathogen (68%). Shigella sonnei comprised 72% and Shigella flexneri 19% of all
      the bacterial isolates. While no antimicrobial resistance to ciprofloxacin was
      found for both Shigella species, only 36 and 26% of the Shigella isolates were
      sensitive to ampicillin and trimethoprim-sulfamethoxazole (TMP-SMZ),
      respectively. These findings point out to the emergence of drug resistance to
      commonly used antimicrobial drugs. Shigella's high sensitivity to the newer
      quinolones should make this the treatment of choice for the very sick patient,
      although physicians should be cautioned to the fact that indiscriminate use of
      this drug could result in the emergence of resistance similar to that noted with
      ampicillin and TMP-SMZ.

PMID- 7804583
TI  - Contaminated casualties: are we prepared to receive them?
AB  - The NHS's reception of casualties contaminated by radiation is reviewed. The
      findings suggest that training, facilities and personal protection for hospital
      staff are inadequate.

PMID- 7804584
TI  - What should doctors wear in the accident and emergency department? Patients'
      perception.
AB  - In many accident and emergency (A&E) departments doctors still wear white coats
      or their ordinary clothes, rather than a type of uniform, which, should it become
      contaminated, can be changed easily for a clean uniform. Before a change of
      clothing to a uniform could be considered in an inner-city A&E department, a
      study was carried out to assess the public's perception towards different styles
      of dress. Three hundred and twenty-nine questionnaires were returned by minor
      injury patients requiring a radiograph. The study was carried out over 3 weeks in
      January 1993. Each week a different style of dress was worn: week 1--white coats,
      week 2--normal clothing and week 3--theatre greens. The majority of patients
      thought that style of dress was important but did not alter their attitude
      towards the A&E medical staff. Therefore, there is no reason why doctors should
      not wear a more appropriate uniform that can be changed easily when contaminated.

PMID- 7804585
TI  - Evaluation of topical ibuprofen cream in the treatment of acute ankle sprains.
AB  - One hundred patients who presented to the accident and emergency (A&E) department
      with an acute ankle sprain were entered into a study to determine the efficacy of
      topical ibuprofen cream by using a double-blind placebo controlled design in a
      single type of soft-tissue injury. The subjects were given either topical
      ibuprofen cream or a placebo cream in addition to the standard management of the
      department. Patients kept diaries recording walking ability and pain visual
      analogue scales for resting, standing and walking. A total of 51 patients
      returned diaries that were suitable for analysis. Patients using the topical
      ibuprofen cream had significant reduction in pain scores over the first 48 h of
      treatment.

PMID- 7804586
TI  - Review of the composition and use of trauma teams within the Trent Region.
AB  - The aim of the study was to find the existence, composition and working policies
      of trauma teams within the Trent Region. Data were obtained by postal survey.
      Despite many reports indicating a need for a unified multidisciplinary approach
      to trauma management, this study found that this approach was absent in many
      hospitals.

PMID- 7804587
TI  - Manipulation under sedation in the accident and emergency department.
AB  - The Royal College of Surgeons of England recently published guidelines for
      sedation by non-anaesthetists. The report emphasizes sedation for endoscopy and
      dental surgery, but the recommendations are equally relevant to accident and
      emergency (A&E) medicine. Current sedation practice for orthopaedic manipulations
      was determined by questionnaire in 58 A&E and orthopaedic junior staff in one
      teaching and one district general hospital. Of the 50 doctors who completed the
      questionnaire, 14 (28%) respondents made an inadequate pre-sedation assessment.
      Over half were unable to name the antagonist to benzodiazepine drugs. Eleven
      (22%) doctors administered supplemental oxygen to all their patients, 12 (24%)
      did not consider it necessary. Pulse oximetry was used for patient monitoring by
      one respondent (2%). None of the junior staff had received any formal training in
      sedation techniques. Thirty-one (62%) had attended a resuscitation refresher
      course within the last year. These results emphasize the need for training in
      sedation techniques for A&E and orthopaedic juniors and the importance of
      appropriate supervision.

PMID- 7804588
TI  - Use of ketamine in prolonged entrapment.
AB  - This paper discusses the advantages of ketamine analgesia in the management of
      trapped patients after serious incidents. Four case histories and a review of the
      literature lead us to the conclusion that ketamine is the drug of choice in these
      situations.

PMID- 7804589
TI  - Monteggia fracture-dislocation in children.
AB  - Monteggia fracture-dislocations are uncommon in childhood. Correct early
      diagnosis is essential to avoid elbow dysfunction and the necessity for open
      reduction of the radial head. This retrospective analysis of 220 forearm
      fractures in children shows that 50% of Monteggia fractures were misdiagnosed by
      accident and emergency (A&E) department senior house officers (SHOs) and 25% were
      misdiagnosed by senior radiologists. Instruction in correct clinical and
      radiological examination of the elbow joint in children to junior A&E doctors,
      with early review of suspicious cases by senior medical staff, may help to reduce
      the incidence of missed Monteggia fractures.

PMID- 7804590
TI  - Non-penetrating corneal foreign body injuries: factors affecting delay in
      rehabilitation of patients.
AB  - A review of 783 patients with non-penetrating, superficial corneal foreign bodies
      (FBs), indicated that delay in rehabilitation was related to two factors: (1) the
      size of the abrasion following removal of the FB, larger abrasions requiring
      longer duration of antibiotic ointment, and (2) inadequate removal of corneal
      rust. Allergy to chloramphenicol 1% ointment (5.5 in 1000), commonly used in the
      management of corneal abrasions, is unpredictable and can also impair rapid
      rehabilitation.

PMID- 7804591
TI  - Acute calcific periarthritis outside the shoulder: a frequently misdiagnosed
      condition.
AB  - Thirteen patients presented to an accident and emergency (A&E) department with
      acute calcific periarthritis of joints other than the shoulder. In only three
      patients was the correct diagnosis made on the initial attendance with
      inappropriate treatment and delay in recovery as a result. The specific features
      and guidelines for management of this condition are reviewed.

PMID- 7804592
TI  - Aluminium ring pulls: an invisible foreign body.
AB  - The aluminium ring pulls associated with the latest designs of drinks cans can be
      relatively easily detached from their mounting on the top of the can and
      subsequently aspirated. Their small size predisposes them to lodge as foreign
      bodies (FBs) in the throat. The similarity of atomic number between soft tissue
      (7.5) and aluminium (13) makes detection of these FBs difficult on soft tissue
      radiography. If aspiration is suspected direct visualization and removal may be
      indicated even if radiography is negative.

PMID- 7804593
TI  - The externally rotated leg: anterior dislocation of the hip.

PMID- 7804594
TI  - Decerebrate posturing in alcoholic coma.
AB  - Two cases of alcoholic coma are presented where extensor responses to noxious
      stimuli are demonstrated. Decerebrate posturing normally indicates severe
      structural or functional depression of midbrain function but can be caused by
      depressant drugs. Blood alcohol measurements are a vital test in the comatose
      patient as the clinical picture may be caused, or temporarily significantly
      worsened, by severe alcohol intoxication. The preservation of pupillary light
      reflexes in the presence of deep coma with decerebrate posturing should alert the
      clinician to a possible metabolic cause for the coma, including alcohol.
      Nevertheless, a diagnosis of alcoholic coma should not be made unless the blood
      alcohol concentration is grossly elevated and other causes of coma have been
      excluded by careful physical examination, blood glucose and electrolyte
      measurement, skull radiography and, in the absence of a rapid improvement,
      computerized tomography.

PMID- 7804595
TI  - The value of otoscopy.

PMID- 7804596
TI  - Injuries sustained by passengers on buses.

PMID- 7804597
TI  - Acute psychiatric disturbance--a side effect of indomethacin therapy.

PMID- 7804598
TI  - The 'light bulb' sign.

PMID- 7804599
TI  - Estradiol treatment increases viability of glioma and neuroblastoma cells in
      vitro.
AB  - The present study provides evidence that 17-beta-estradiol (E2) exerts
      cytoprotective effects on both glial and neuronal cell lines. In C6 rat glioma
      cells, the addition of E2 to serum free media enhances live cell number by 40% at
      24 h and 75% at 96 h when compared to serum free media conditions. E2 treatment
      of C6 cells in serum free medium did not increase thymidine uptake at any
      sampling time, indicating that the observed effect of E2 on C6 cell number was
      not due to a mitogenic effect of the steroid hormone. The addition of E2 to SK-N
      SH cells in serum free media maintained both total and live cell number at a
      level comparable to the fetal bovine serum (FBS) treated cells at both 24 and 48
      h. At 96 h after treatment with E2, total and live cell numbers were diminished
      relative to the 48-h sample and the 96-h FBS group, but were still more than
      twice the number observed in serum free media. Associated with the reduced
      effects of E2 at 96 h was an increase in the ratio of dead to total cells,
      although it remained about 50% less than the serum free group. Through 48 h, E2
      exposure did not increase thymidine uptake in SK-N-SH cells, indicating that the
      effect of E2 on SK-N-SH cells was cytoprotective rather than mitogenic.
      Collectively, these data support a cytoprotective action of E2 on neuronal or
      glial cell types in vitro.

PMID- 7804600
TI  - Characterization of the chicken rhodopsin promoter: identification of retina
      specific and glass-like protein binding domains.
AB  - The rhodopsin promoter was analyzed as a prototype for cis-acting DNA elements
      involved in photoreceptor-specific gene regulation. We report the isolation and
      sequence of 1.8 kb of 5' flanking sequence of the chicken rhodopsin gene and
      analysis of DNA-binding proteins to promoter fragments by gel retardation assay.
      These analyses identified retina- and brain-specific protein binding to several
      regions of the rhodopsin promoter both proximal and distal to the transcription
      start site. The tissue-specific protein binding patterns were consistent with
      that proposed previously based on the expression pattern of rhodopsin promoter
      lacZ constructs in transgenic mice (1, 2). The data also confirm the presence of
      the chicken homolog to a rat retina-specific binding site in the proximal
      promoter described previously. The Drosophila glass gene, which encodes a site
      specific DNA-binding zinc-finger protein, is known to be required for the normal
      development of all photoreceptors in this species (3). In this paper we identify
      a glass-like sequence motif in chick, which shows homology to the Drosophila Rh1
      27-bp glass-binding sequence, and find that the chick glass-like element exhibits
      tissue-specific protein binding properties which parallel those observed with
      Drosophila glass.

PMID- 7804601
TI  - Dose-dependent selective suppression of light (NFL) and medium (NFM) but not
      heavy (NFH) molecular weight neurofilament mRNA levels in acute aluminum
      neurotoxicity.
AB  - We inoculated 5- to 6-week old New Zealand white rabbits intracisternally with
      either 100, 250, 500, 750, or 1000 micrograms of AlCl3 or 0.9% NaCl and
      correlated the extent of cervical motor neuron neurofilamentous inclusion
      formation at 48 h postinoculation with alterations in neurofilament (NF) mRNA
      levels. RNA was isolated from cervical spinal cord by the guanidine
      isothiocyanate method and individual RNA samples were normalized for poly(A+)
      content. Northern blot analysis was performed with cDNA probes for light (NFL),
      medium (NFM), and heavy (NFH) neurofilament subunit protein or with
      oligonucleotide probes for alpha-tubulin or actin. No significant alteration in
      the levels of alpha-tubulin, actin, or NFH mRNA were observed, regardless of the
      aluminum dose. In contrast, dose-dependent reductions in NFL and NFM mRNA levels
      occurred in direct proportion to the extent of neurofilamentous inclusion
      formation. While inoculums of NaCl or 100 or 250 micrograms AlCl3 induced neither
      inclusion formation or alterations in mRNA levels, both inclusion formation and
      reductions in the levels of NFL and NFM mRNA occurred thereafter, becoming
      maximal with inoculums of 1000 micrograms AlCl3. These experiments indicate that
      intracisternally administered AlCl3 acutely suppresses NFL and NFM mRNA levels
      without affecting those of NFH. This pattern is in distinct contrast to the
      uniform reductions of all NF mRNA transcript levels during neurogenesis or
      following axotomy, indicating a specific effect of aluminum upon steady-state
      levels of NF mRNA that correlates with the induction of neurofilamentous
      aggregates.

PMID- 7804602
TI  - Distribution of kappa opioid receptor mRNA in adult mouse brain: an in situ
      hybridization histochemistry study.
AB  - The distribution of the kappa opioid receptor mRNA in adult mouse brain has been
      determined using the technique of in situ hybridization histochemistry. The mRNA
      for the kappa opioid receptor was expressed in distinct areas throughout the
      brain. The telencephalon showed high levels of expression in the deeper layers of
      the parietal and temporal cortex, olfactory tubercle, nucleus accumbens,
      claustrum, endopiriform nucleus, nucleus of the vertical and horizontal limb of
      the diagonal band, and medial and central nuclei of the amygdala. In the
      diencephalon, kappa opioid receptor mRNA was present in multiple medial thalamic
      nuclei including the centromedial, paraventricular, parafasicular, central, and
      peritenial nuclei, as well as in most hypothalamic nuclei including the
      ventromedial, periventricular, supraoptic, arcuate, and dorsomedial nuclei. The
      mesencephalon showed highest levels of kappa receptor mRNA in the substantia
      nigra pars compacta, ventral tegmental area, zona incerta, interpeduncular
      nucleus, superior colliculus, inferior colliculus, central grey, and the raphe
      nucleus. In the metencephalon, kappa opioid receptor mRNA was expressed in the
      parabrachial nuclei, locus coeruleus, dorsal and ventral tegmental nuclei, and
      the raphe pontine nuclei. The distribution of the kappa receptor mRNA closely
      coincides with the localization of binding sites in rat brain for [3H]U-69,593, a
      specific kappa 1 opioid receptor ligand. The mRNA distribution also correlates
      with neuroanatomical sites of actions of kappa agonists and distribution of the
      endogenous kappa receptor ligand dynorphin.

PMID- 7804604
TI  - Effect of hypophysectomy on corticotropin-releasing hormone and
      adrenocorticotropin immunoreactivities in the rat adrenal gland.
AB  - It has previously been shown that rat adrenal zona medullaris possesses an
      interleukin-1 beta (IL-1 beta)-responsive peripheral branch of the CRH/ACTH
      system that duplicates the hypothalamopituitary central one (Mazzocchi et al.,
      Mol. Cell. Neurosci. 4: 267, 1993). The intraadrenal content of corticotropin
      releasing hormone (CRH) and adrenocorticotropin (ACTH) immunoreactivities (ir),
      as well as IL-1 beta-stimulated release of CRH-ir and ACTH-ir, increased in
      relation to the number of days elapsed from hypophysectomy; the effect of
      hypophysectomy required at least 48 h to become significant and reached its
      maximum after 72 h. The action of IL-1 beta on ACTH-ir release was annulled by
      simultaneous exposure to alpha-helical-CRH, an antagonist of CRH. ACTH infusion,
      at a rate restoring a normal blood level of the hormone, prevented the effect of
      hypophysectomy on intraadrenal concentrations of both CRH-ir and ACTH-ir;
      similarly, the hypophysectomy-evoked rise in intraadrenal ACTH-ir content was
      completely annulled by treating hypophysectomized rats with CRH or dexamethasone.
      Taken together our findings suggest that the elimination of the central branch of
      CRH/ACTH system induces a marked increase in the activity of the intraadrenal
      peripheral one. The hypothesis is advanced that the hypophysectomy-induced
      lowering of circulating ACTH and the consequent drop in the production of adrenal
      glucocorticoids enhances, via a classic negative feedback mechanism, gene
      expression of CRH and ACTH in adrenal medullary chromaffin cells.

PMID- 7804603
TI  - c-fos antisense oligonucleotide specifically attenuates haloperidol-induced
      increases in neurotensin/neuromedin N mRNA expression in rat dorsal striatum.
AB  - Acute administration of neuroleptic drugs such as haloperidol robustly increases
      transcription of the gene encoding the neuroactive peptide, neurotensin, in the
      dorsolateral striatum of the rat. This induction of neurotensin/neuromedin (NT/N)
      mRNA by haloperidol is preceded by increases in c-fos mRNA expression in the same
      region. Our recent studies demonstrate that a vast majority of haloperidol
      sensitive NT/N mRNA expressing cells in the dorsolateral striatum coexpress c-fos
      mRNA. These data suggest that the transcription factor, Fos, may participate in
      NT/N gene induction by neuroleptics. Present studies investigated this
      possibility using an antisense c-fos oligodeoxynucleotide (which has been shown
      to block the expression of Fos protein in vivo) or its sense sequence oligomer
      injected into opposite caudate-putamen of awake, freely moving rats. Eight hours
      following the injection of the oligomers, the animals were challenged with a
      systemic injection of haloperidol (1 mg/kg) and were sacrificed 1 h later.
      Examination of NT/N mRNA by in situ hybridization histochemistry revealed
      approximately 50% attenuation in the NT/N mRNA expression in the dorsolateral
      striatum injected with the antisense oligomer compared to the contralateral side
      which received the sense oligomer. On the other hand, expression of proenkephalin
      mRNA in the dorsolateral striatal neurons or NT/N mRNA in the nucleus accumbens
      shell was not altered following the c-fos antisense oligomer injection. These
      data demonstrate a specific role of Fos in the regulation of the
      neurotensin/neuromedin N gene in the rat dorsolateral striatal neurons by acute
      haloperidol treatment.

PMID- 7804605
TI  - Calcium channel subtypes in rat brain: biochemical characterization of the high
      affinity receptors for omega-conopeptides SNX-230 (synthetic MVIIC), SNX-183
      (SVIB), and SNX-111 (MVIIA).
AB  - High-threshold voltage-sensitive calcium channels of the N-type, L-type, and P
      type have been distinguished in the mammalian CNS predominantly on the basis of
      their sensitivity to selective antagonists. Matching them with genes identified
      by molecular cloning is an ongoing undertaking. Whereas L-type channels are
      characterized by their sensitivity to dihydropyridines and P-type channels by
      sensitivity to the funnel-web spider toxin AgaIVA, the N-type channel has been
      shown to be recognized by the omega-conopeptides GVIA and MVIIA. Recently, two
      new members of the family of omega-conopeptides--MVIIC from the marine snail
      Conus magus and SVIB from Conus striatus--have been described. Binding and
      electrophysiological data suggest that these two peptides, in addition to
      interacting with N-type calcium channels, interact with a widely distributed
      receptor in neuronal membranes that is distinct from N-type channels. In this
      report we demonstrate through biochemical and pharmacological differentiation at
      individual receptor polypeptide resolution, by affinity cross-linking, SDS-PAGE,
      and autoradiography, that SNX-230 (synthetic MVIIC) binds with high affinity to a
      calcium channel alpha 1 subunit distinct from the high-affinity alpha 1 target of
      SNX-111 (synthetic MVIIA). SNX-183 (synthetic SVIB) interacts with both alpha 1
      subunits with lower affinity. Whereas the alpha 1 subunit recognized with high
      affinity by MVIIA corresponds to the N-type channel, the other represents a novel
      calcium channel distinct from N-, L-, and perhaps P-type channels.

PMID- 7804606
TI  - Differential sensitivity to inhibitors discriminates between two types of kinases
      responsible for in vivo phosphorylation of different sites in the carboxy
      terminal tail of chicken neurofilament-M.
AB  - In order to characterize the phosphorylation of neurofilaments (NF) in intact
      neurons, we examined the ability of several protein kinase inhibitors to
      interfere with the incorporation 32P into individual NF polypeptides of sensory
      neurons in culture. We also examined their effect on the post-translational
      mobility shift on SDS-PAGE that accompanies phosphorylation of newly synthesized
      NF-M. Several agents known to inhibit cyclic nucleotide-, Ca2+/calmodulin-, and
      Ca2+/phospholipid-dependent protein kinases (H7, HA1004, trifluoperizine,
      sphingosine) had no effect on the phosphorylation of any NF polypeptide, in
      either assay. In contrast, two broadly active protein kinase inhibitors,
      staurosporine and K252a, inhibited the incorporation of 32P into NF-M by 60-70%
      and also blocked the post-translational mobility shift. They had no effect on NF
      L. The action of staurosporine and K252a was identical to that of 25 mM LiCl.
      Proteolytic cleavage and phosphopeptide mapping of 32P-labeled NF-M from control
      and treated cultures revealed that the phosphorylation of only one subset of
      phosphopeptides was affected by staurosporine, K252a, and LiCl. These were
      contained within a single chymotryptic fragment of the NF-M tail segment,
      probably containing most of the 17 repeats of a KXXS/TP motif. The
      phosphorylation of another subset of phosphopeptides was insensitive to these
      inhibitors. They were contained within a different chymotryptic fragment of the
      tail segment which contains a KSD and four KSP potential phosphorylation sites.
      This differential sensitivity to protein kinase inhibitors distinguishes two
      different types of effector-independent kinases that phosphorylate, in vivo,
      different sites within the NF-M tail.

PMID- 7804607
TI  - Modulation of expression of glucose transporters GLUT3 and GLUT1 by potassium and
      N-methyl-D-aspartate in cultured cerebellar granule neurons.
AB  - Depolarization is known to stimulate neuronal oxidative metabolism. As glucose is
      the primary fuel for oxidative metabolism in the brain, the entry of glucose into
      neural cells is a potential control point for any regulatory events in brain
      metabolism. Therefore, the effects of depolarizing stimuli, high K+ and N-methyl
      D-aspartate (NMDA), were examined on the functional expression of glucose
      transporter isoforms GLUT1 and GLUT3 in primary cultured cerebellar granule
      neurons. Higher levels of glucose transport activity were observed in neurons
      cultured in 25 mM KCl (K25) compared to those in 5 and 15 mM KCl (K5 and K15).
      The elevated glucose transport activity correlated with increased levels of GLUT3
      protein and, to a lesser extent, GLUT1. Both GLUT3 and GLUT1 were regulated at
      the level of mRNA expression. Addition of NMDA to K5 and K15 cultures increased
      both glucose uptake and GLUT3 protein levels, with smaller changes in GLUT1. NMDA
      effects were not additive with K25 effects. All these changes were observed only
      with chronic exposure of neurons to high K+ or NMDA; no acute effects on glucose
      uptake or transporter expression were found. Thus, chronic depolarization of
      primary cerebellar granule neurons acts as a stimulus for the expression of the
      neuronal GLUT3 glucose transporter isoform.

PMID- 7804608
TI  - Regional distinction in age-related changes of preoptic regulatory factor-1 and
      preoptic regulatory factor-2 mRNA expression in the rat brain.
AB  - Preoptic regulatory factor-1 (porf-1) and preoptic regulatory factor-2 (porf-2)
      are two novel neuropeptide genes expressed in the central nervous system and
      peripheral tissues. Other studies have shown that these genes may play a role in
      steroid-dependent brain development and functions. In this study, nuclease
      protection assays were employed to investigate Porf-1 and Porf-2 mRNA expression
      in male rat brains of different ages. The preoptic area (POA), cerebral cortex
      (CC), and hippocampus (HIPP) expressed both Porf-1 and Porf-2 mRNA, while only
      Porf-2 mRNA was detectable in the medial basal hypothalamus (MBH). Porf-1 mRNA in
      the POA was highest at the age of 2 months (young adult), decreased at the age of
      6 months (mature adult), and remained low at the ages of 12 (middle aged) and 24
      months (aged). Porf-1 mRNA in the CC was also the highest at the age of 2 months
      and decreased with age. However, there were no age-related changes for Porf-1
      mRNA in the HIPP. Porf-2 mRNA in the HIPP was found to be low at the age of 2
      months, increased at the ages of 6 and 12 months, and decreased at the age of 24
      months. The effect of age on Porf-2 mRNA in the POA was similar to that seen for
      Porf-1, with the highest expression observed in the 2-month-old rats. There were
      no age-related Porf-2 mRNA changes in the MBH and CC. These results indicate
      differential regulation of expression of the porf-1 and porf-2 genes in the MBH,
      POA, HIPP, and CC. The possible roles of these two genes in maturation and aging
      of male rats are discussed.

PMID- 7804609
TI  - Enhanced auditing techniques using a local area network.

PMID- 7804610
TI  - How total quality impacted SOPs.

PMID- 7804611
TI  - Looking back--a history of progress: Society of Quality Assurance.
AB  - The Society of Quality Assurance (SQA) Historical Committee has tracked the
      impressive evolution of our society from the initial sharing of ideas at the 1980
      Quality Assurance Roundtable meeting to the formation of the national SQA in
      1984, to a 12-fold increase in membership numbers through 1993. This article
      describes annual meeting locations and attendance, membership numbers, and
      organizational information, as well as significant milestones for both the
      Quality Assurance Roundtable group and the SQA.

PMID- 7804612
TI  - Strategies for achieving total quality--the Corning experience.

PMID- 7804613
TI  - Customer focus and satisfaction.

PMID- 7804614
TI  - Innovation and compliance are not diametrically opposed.

PMID- 7804615
TI  - Computer validation vendor audits.

PMID- 7804616
TI  - The role of quality assurance in computer inspections.
AB  - Changing technology affords the Quality Assurance auditor with the challenge of
      applying computer validation concepts to a variety of computer system types. In
      addition, these technology changes have caused the developers role to change as
      well. In an innovative research facility, the developer may include an in-house
      professional group, a vendor, or an end-user. With these issues in mind, the QA
      auditor needs a tool to accomplish the task of inspecting systems as they are
      being created. The prospective inspection process is the tool for accomplishing
      this task. This inspection involves the QA auditor's involvement in the
      development of a new system, as a member of the development team, from the
      initial creation through the implementation of the computer system. This
      presentation will focus on illustrating the steps in conducting the prospective
      inspection process, from expected deliverables and document reviews to final
      report and management notification. The benefits of QA involvement in the
      development process will also be discussed.

PMID- 7804617
TI  - Quality assurance auditors: how to survive between a rock and a hard place.

PMID- 7804618
TI  - Occupational exposure to hazardous chemicals in laboratories (29 CFR 1910.1450).

PMID- 7804619
TI  - The ISSI method of perpetual standard operating procedures (SOPs).

PMID- 7804620
TI  - Using measures to guide the continuous improvement journey: a partnership between
      quality assurance and toxicology.
AB  - It has been said that you cannot improve what you cannot measure. At Eli Lilly
      and Company, measurement is one of the five pillars of Total Quality. Quality
      Assurance and Toxicology have partnered in the use of measures to drive
      improvements in both areas. Quality Assurance and Toxicology have embarked on a
      journey in Total Quality to achieve customer satisfaction and drive continuous
      improvement. Measurement in the research and development world has traditionally
      not been well received. Contrary to popular belief, we have found that many
      processes can be measured in the research and development environment.
      Measurement is critical to the continuous improvement of processes because
      improvements are made using data. In Quality Assurance and Toxicology, the
      initial measures were put in place to gather baseline data. As we learned from
      our measures, we customized them to align with all of our processes. This article
      describes the journey of measuring Quality Assurance and Toxicology, including
      highlights of implementation strategies and lessons learned along the way.

PMID- 7804621
TI  - The application of quality assurance to total quality management. Development of
      14C-based analytical methods for metabolism and environmental fate studies at
      RTP.

PMID- 7804622
TI  - Code of Federal Regulations (CFRs): where it all begins.

PMID- 7804623
TI  - GLP awareness: concepts, pedagogy, and benefits.

PMID- 7804624
TI  - Beyond compliance.

PMID- 7804625
TI  - Tracking of reports and workload through the Quality Assurance Unit.
AB  - In summary, this documentation has aided the QA Unit in several ways. First, it
      has created a method for documenting and establishing the need for additional QA
      personnel as workload increases. Second, it serves as a tool for evaluating the
      individual performance of the QA Auditors. Third, it documents the individual
      reports as to when they were received and released by QA, forming a chain of
      custody for the reports.

PMID- 7804626
TI  - The use of flow charting to improve processes in quality assurance.

PMID- 7804627
TI  - Good clinical practices.

PMID- 7804628
TI  - U.S. FDA regulatory challenges and review.

PMID- 7804629
TI  - Pharmaceutical GMPs.

PMID- 7804630
TI  - Performing GLP studies in a traditionally non-GLP facility.
AB  - Situations can arise in which traditionally non-GLP facilities may have to be
      used for performing nonclinical GLP studies or parts of a GLP study. The
      situations may include a need for particular expertise of scientists, the
      analytical laboratory, or the development of an unusual product. This article
      describes the use of a core group model as a proactive strategic plan to bring
      the traditionally non-GLP facility into compliance before the GLP study is
      conducted. The core group team is composed of representatives of both the Sponsor
      and the facility where the GLP study will be conducted. The core group model uses
      a nine-step plan that fosters good communication, co-operative planning, and
      adequate preparation before initiation of a proposed GLP nonclinical study,
      conducted under GLP compliance, at a traditionally non-GLP facility.

PMID- 7804631
TI  - Facility capability assessment.
AB  - An inspection and evaluation procedure has been developed to assess the
      capabilities of contract toxicology laboratories. This procedure has been used
      for the inspection of 18 different contract toxicology laboratories. There are 10
      areas inspected: 1. Facility 2. Personnel 3. Operations 4. Animals/Animal Care 5.
      Standard Operating Procedures 6. Quality Assurance 7. Equipment 8. Test Article
      9. Data 10. Archives. Each of these areas is divided into categories with each
      category divided further into specific topics. Points are assigned to each topic.
      The points earned by the laboratory reflect the inspector's assessment of the
      laboratory's quality in each area. Area scores are added and a percentage score
      for the facility is calculated. This approach provides a clear distinction among
      the laboratories evaluated. The facility inspection and rating system played an
      important role in screening laboratories when the author worked for the Atlantic
      Richfield Company (ARCO) corporate toxicology department. It highlighted
      strengths and weaknesses of individual laboratories.

PMID- 7804632
TI  - Regulatory challenges for in vitro diagnostics in a global environment.
AB  - U.S. medical products are marketed globally and are designed to meet needs of
      medical practitioners and their patients throughout the world. However,
      differences in how these products are regulated in different countries can pose
      challenges for the global marketer. This paper explores some of the differences
      between proposed and extant U.S. and European regulations for in vitro diagnostic
      products in terms of documentation, records, and labelling. It will describe some
      of the practical implications of these differences.

PMID- 7804633
TI  - Quality assurance and the drug development process: an FDA perspective.

PMID- 7804634
TI  - Computer validation life cycle.

PMID- 7804635
TI  - Statistical auditing of toxicology reports.
AB  - Statistical auditing is a new report review process used by the quality assurance
      unit at Eli Lilly and Co. Statistical auditing allows the auditor to review the
      process by which the report was generated, as opposed to the process by which the
      data was generated. We have the flexibility to use different sampling techniques
      and still obtain thorough coverage of the report data. By properly implementing
      our auditing process, we can work smarter rather than harder and continue to help
      our customers increase the quality of their products (reports). Statistical
      auditing is helping our quality assurance unit meet our customers' need, while
      maintaining or increasing the quality of our regulatory obligations.

PMID- 7804636
TI  - Auditing drug metabolism protocols, data, and reports.
AB  - A critical component of the drug discovery process is to assess the safety and
      metabolic disposition of a drug. This can be accomplished by evaluating drug
      concentration levels as part of safety assessment studies (toxicokinetics) and
      identifying the drug's presence in and throughout the body by conducting ADME
      (adsorption, distribution, metabolism, and excretion) studies. From a regulatory
      perspective, the major difference between these two types of evaluations is that
      toxicokinetic studies are under the purview of the Good Laboratory Practice (GLP)
      regulations (21 CFR 58) and ADME studies are not. International debate continues
      to resolve around the need to consider the applicability of the GLPs to ADME
      studies. While it is recognized that the current regulatory intent between ADME
      and toxicokinetic studies differs, this inspecting/auditing approach treats them
      generally the same. It assures management and external reviewers that data
      integrity measures are in place for all drug metabolism studies conducted by the
      facility.

PMID- 7804637
TI  - The role of quality assurance in a university laboratory: the first year.

PMID- 7804638
TI  - Analytical data capture system validation in a preclinical/clinical laboratory.

PMID- 7804639
TI  - Monsanto's computer animal proposal system (CAPS).
AB  - Regulations and standards must include the minimum requirements with respect to
      veterinary care, sanitation, handling, feeding, and housing. Part 1 of the Animal
      Welfare Act regulations was amended to update, clarify, and expand the list of
      definitions of terms and standards. Section 9 CFR, Part 1, contains definitions
      and deals with animal welfare, animal housing, dealers, exhibitors, research
      facilities, and humane animal handling. The subjects in 9 CFR, Part 2, pertain to
      licensing, registration, identification of animals, records, institutional animal
      care and use committees, and adequate veterinary care. Animal welfare, humane
      animal handling, pets, transportation, and reporting and recordkeeping
      requirements are the subjects listed in 9 CFR, Part 3.

PMID- 7804640
TI  - The procedure for generating a quality, integrated clinical/statistical study
      report.

PMID- 7804641
TI  - U.S. EPA regulatory challenges and review.
AB  - Regulatory and program developments during the past year are reviewed. These
      include the Good Laboratory Practices (GLP) enforcement case initiative, the
      implications of the Bio-Tek Industries decision, and the status of the Craven
      Laboratories case. The status of the Agency's laboratory accreditation workgroup
      is discussed, as well as the responses to date to the Inspector General's reports
      on EPA's GLP program. Internal improvements in GLP inspection procedures and the
      case review process are highlighted. The year's noteworthy events in the
      international arena conclude the talk.

PMID- 7804642
TI  - Recent and current EPA good laboratory practice policy issues.
AB  - The Policy and Grants Division of the Office of Compliance Monitoring and
      specifically the Pesticides Enforcement Policy Branch (PEPB) of that division
      were active in policy issues affecting GLPs throughout the past year. Among the
      products have been a number of correspondences which have been made available to
      the regulated community--edited to preserve the confidentiality of persons
      writing to the agency--as "advisories." In addition, the PEPB actively worked
      with members of the regulated community to assist in their compliance with the
      GLPs. These two areas, GLP policy guidance during the last year and compliance
      assistance efforts, are discussed below. Note that recently there have been
      organizational changes at EPA, and policy issues originally covered by the
      Pesticides Enforcement Policy Branch are now addressed by the new Agriculture
      Branch of the Agriculture and Ecosystems Division. This division is in the Office
      of Compliance of the newly formed Office of Enforcement and Compliance Assurance.
      This organizational change will not adversely affect EPA responsiveness on GLP
      policy matters.

PMID- 7804643
TI  - Laboratory accreditation.
AB  - An investigation of alleged data fraud at a pesticide analytical laboratory led
      EPA to take a closer look at the Good Laboratory Practice (GLP) inspection
      program. There was special focus on changes which might be made in the program to
      enhance the chances of detecting fraud in regulated studies. To this end, the
      Assistant Administrator of the Office of Prevention, Pesticides and Toxic
      Substances (OPPTS) requested EPA's Office of Inspector General (OIG) to examine
      the GLP program. Several reports were issued by the OIG, including the
      recommendation that a laboratory accreditation program be adopted. EPA has been
      examining ways to implement the OIG's recommendations, including (1) laboratory
      accreditation consisting of three components: document submission and assessment,
      site visit and assessment, and proficiency assessment; and (2) mandatory
      registration of all facilities participating in GLP-regulated studies, based on
      document submission and assessment. These two alternatives are compared, and the
      advantages and disadvantages of each are discussed.

PMID- 7804644
TI  - The role of quality in today's research university.
AB  - Today's research universities strive to meet goals in education, research, and
      service within an academic environment. A quality assurance and quality control
      program is critical to achieving excellence in all areas. However, the role of
      quality in research at higher education institutions is difficult to determine or
      consistently implement due to the broad nature of the research and academic
      goals. In addition, it is compounded by the loose organizational structure common
      to most universities. Formal quality assurance programs are not historically
      found at academic institutions. Faculty and staff often have neither the
      experience nor training in good quality assurance practices. Implementation of a
      formal quality assurance program is made more difficult by university space and
      financial limitations and a reward system based on peer-reviewed publications. A
      successful formal quality assurance program must be sufficiently flexible to meet
      all needs, must focus on those needs, and must be willingly supported by all
      participants. The Institute of Wildlife and Environmental Toxicology (TIWET) at
      Clemson University in South Carolina has implemented a quality assurance program
      designed to comply with several quality assurance regulations, including the good
      laboratory practice (GLP) standards. The program relies on study protocols or
      plans, standard operating procedures (SOPs), data collection forms, a quality
      assurance manual, quality assurance checklist/plans, and a quality assurance
      unit. The program maximizes flexibility while complying with several quality
      regulations and consensus standards. Since implementation, improvements in
      communication, study design, data recording, and reporting have been
      noted.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7804645
TI  - The interregional research project #4 (IR-4).

PMID- 7804646
TI  - Field phase.

PMID- 7804647
TI  - Processing of samples.
AB  - The Good Laboratory Practice (GLP) Processing Program at Texas A&M University
      provides a service that encompasses research and pilot scale processing of raw
      agricultural commodities while conforming to the Federal Insecticide, Fungicide,
      and Rodenticide Act (FIFRA), 40 CFR, Part 160. A general overview of a typical
      processing study is presented to include preliminary discussions with the study
      director, sample and protocol receipt, sample processing, fraction shipment, and
      processing report disposition. Atypical situations are also introduced to stress
      the need for improved communication and organization within the agrochemical
      industry. Examples of processed fractions are presented to clarify better the
      role of the processor in the chemical registration process. To describe the
      versatility required within this segment of the registration process, a new
      processing procedure is introduced.

PMID- 7804648
TI  - Worker exposure studies.
AB  - The first federal pesticide law was enacted in 1910 and was replaced by a more
      expansive Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) in 1947. In
      1972 the Federal Environmental Pesticide Control Act amended the FIFRA from
      primarily a consumer protection law to a risk/benefit regulation with primary
      emphases on human and environmental health. "Modern" pesticides were beginning to
      be developed during World War II. Early attempts to assess human exposure to
      pesticides seemed to coincide with the development of the organophosphate
      pesticides in the early to mid 1950s. A continually expanding base of
      toxicological knowledge has forced increased efforts to refine exposure
      assessments. Early "patch" dosimeters have evolved to numerous and more refined
      methods of dosimetry. In addition to studying worker exposure, modern students of
      pesticide application must also deal with a myriad of situations ranging from
      field or site reentry to bystander and/or residential exposures. Efforts to
      standardize pesticide exposure assessments resulted in the 1987 issuance of U.S.
      EPA Pesticide Assessment Guidelines--Subdivision U--Applicator Exposure
      Monitoring. In October, 1989 (40 CFR Part 160), the Agency directed that studies
      initiated on or after that date and submitted in support of pesticide regulation
      must be conducted under the standards of Good Laboratory Practices. All of these
      and related factors culminate in the continued development and refinement of
      methodologies for pesticide exposure assessment.

PMID- 7804649
TI  - Sample tracking in analytical chemistry residue laboratories.

PMID- 7804650
TI  - Pesticide registration in the United States: overview and new directions.
AB  - This paper provides an overview of EPA's pesticide registration program and a
      discussion of recent activities. The registration of pesticides is the
      responsibility of the Office of Pesticide Programs, an office of the U.S.
      Environmental Protection Agency (EPA). EPA's pesticide regulatory authority
      derives from the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) and
      the Federal Food, Drug and Cosmetic Act (FFDCA). FIFRA governs the registration
      or licensing of pesticide products including insecticides, herbicides,
      fungicides, rodenticides, disinfectants, plant growth regulators, and biological
      agents. FFDCA governs pesticide residue levels in food and feed crops. FIFRA
      gives EPA authority for registering pesticides to ensure that when used according
      to label directions, they will not pose unreasonable adverse effects to the
      environment. FIFRA requires EPA to balance the risks and benefits of a pesticide
      in deciding whether or not to grant a pesticide registration. In a typical year
      EPA reviews over 5000 registration submissions that vary from routine label
      amendments to the review of a new active ingredient. About 20 applications for
      registration of a new active ingredient are received each year. Registration for
      a new active ingredient requires a significant investment in time and money by
      the registrant. Data development for a major agricultural chemical can cost 10
      million dollars or more and take several years to complete. EPA is embarking on a
      number of new initiatives in the registration program designed to reduce the use
      of chemical pesticides, limit the regulatory burden on lower risk and reduced
      risk products, and streamline the review process generally.

PMID- 7804651
TI  - Customized dual data entry for computerized data analysis.
AB  - A major responsibility of any Quality Assurance Unit (QUA) is to ensure data
      integrity. Errors made during data entry can lead to many problems in the study
      review process and decrease the quality, accuracy, and overall efficiency of data
      management. One technique that can reduce the number of data entry errors in
      computer data sets is the use of a dual entry data system. Currently available
      software allows creation of customized data entry screens that either closely
      resemble or duplicate the data collection forms used during studies. Two data
      entry operators enter data into two independent data sets. The use of an on
      screen display that resembles the data collection form reduces the potential for
      keypunch errors. The two data sets can then be electronically compared. The
      comparison reports differences between the two data sets. When differences exist,
      the correct values can be determined by reference to the original data sheets and
      the two data files can then be corrected. Theoretically, the only key punch
      errors that will exist after making these corrections are when the two
      independent entry operators make the same exact data entry error. Typically, the
      time required for two people to enter data is minimal compared to the time
      required to manually identify and correct data entry discrepancies. With error
      free data entry, we have found that electronic data quality, accuracy, and audit
      efficiency are improved at every subsequent step of data management, analysis,
      quality assurance auditing, and report generation.

PMID- 7804652
TI  - Integrating QA principles with basic elements of a research program promotes
      quality science in a non-GLP research laboratory.

PMID- 7804653
TI  - Harmonization of good laboratory practice requirements and laboratory
      accreditation programs.
AB  - Efforts to harmonize Good Laboratory Practice (GLP) requirements have been
      underway through the Organization for Economic Cooperation and Development (OECD)
      since 1981. In 1985, a GLP panel was established to facilitate the practical
      implementation of the OECD/GLP program. Through the OECD/GLP program, Memoranda
      of Understanding (MOU) agreements which foster requirements for reciprocal data
      and study acceptance and unified GLP standards have been developed among member
      countries. Three OECD Consensus Workshops and three inspectors training workshops
      have been held. In concert with these efforts, several OECD countries have
      developed GLP accreditation programs, managed by local health and environmental
      ministries. In addition, Canada and the United States are investigating
      Laboratory Accreditation programs for environmental monitoring assessment and GLP
      regulated studies. In the European Community (EC), the need for quality standards
      specifying requirements for production and international trade has promoted
      International Standards Organization (ISO) certification for certain products.
      ISO-9000 standards identify requirements for certification of quality systems.
      These certification programs may affect the trade and market of laboratories
      conducting GLP studies. Two goals identified by these efforts are common to both
      programs: first, harmonization and recognition of requirements, and second,
      confidence in the rigor of program components used to assess the integrity of
      data produced and study activities. This confidence can be promoted, in part,
      through laboratory inspection and screening processes. However, the question
      remains, will data produced by sanctioned laboratories be mutually accepted on an
      international basis?(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7804654
TI  - Reform of mental health care in Europe. Progress and change in the last decade.

PMID- 7804655
TI  - Culture and schizophrenia. Criticisms of WHO studies are answered.

PMID- 7804656
TI  - 'Universality of mental illness' revisited: assumptions, artefacts and new
      directions.

PMID- 7804657
TI  - 'Psyche'--spirit as well as mind?

PMID- 7804658
TI  - Clinical and psychosocial origins of chronic depressive episodes. I: A community
      survey.
AB  - BACKGROUND: We consider how far it is possible to predict a chronic course of a
      depressive disorder from psychosocial and clinical material available at the
      point of onset. METHOD: A population survey found 404 working-class mothers
      living in an inner-city area of London. The majority were interviewed three times
      over a 3-year period. RESULTS: Chronicity (more than 12 months' duration) was
      strongly related to both childhood adversity (parental indifference, family
      violence or any sexual abuse) and current adult interpersonal difficulties. The
      lack of positive events during the course of the episode was also independently
      related to chronicity, but to a lesser degree. Clinical characteristics were
      relatively unimportant compared with psychosocial factors. CONCLUSIONS: The
      childhood risk factors were particularly important (judged by a path analysis),
      and a challenge for future research will be to establish the intervening
      processes involved with this distal link.

PMID- 7804659
TI  - Clinical and psychosocial origins of chronic depressive episodes. II. A patient
      enquiry.
AB  - BACKGROUND: We consider how well the psychosocial and clinical factors found to
      predict a chronic course for depressive episodes in the community, held for
      female psychiatric patients. METHOD: A consecutive series of depressed patients,
      aged 18 to 60, treated as in-patients, out-patients or day-patients at
      psychiatric departments of two London hospitals, were interviewed initially and
      at follow-up two years later. RESULTS: Indices of childhood adversity and current
      interpersonal difficulties predicted episodes taking a chronic course (of more
      than 12 months' duration). Half of the episodes associated with one or the other
      factor were chronic, compared with 22% of those with neither. The patients were
      at higher risk than the community series (75% v. 34%) and this explains their
      much greater rate of chronicity. There was also some evidence that social support
      reduced risk. Clinical features and the presence of a personality disorder were
      unrelated to chronicity. CONCLUSIONS: Similar psychosocial factors are important
      for predicting chronicity in both community and patient series.

PMID- 7804660
TI  - Age at onset, sex, and familial psychiatric morbidity in schizophrenia.
      Camberwell Collaborative Psychosis Study.
AB  - BACKGROUND: Although a genetic component in schizophrenia is well established, it
      is likely that the contribution of genetic factors is not constant for all cases.
      Several recent studies have found that the relatives of female or early onset
      schizophrenic patients have an increased risk of schizophrenia, compared to
      relatives of male or late onset cases. These hypotheses are tested in the current
      study. METHOD: A family study design was employed; the probands were 195 patients
      with functional psychosis admitted to three south London hospitals, diagnosed
      using Research Diagnostic Criteria (RDC), and assessed using the Present State
      Examination (PSE). Information on their relatives was obtained by personal
      interview of the mother of the proband, and from medical records. Psychiatric
      diagnoses were made using Family History-Research Diagnostic Criteria (FH-RDC),
      blind to proband information. RESULTS: There was a tendency for homotypia in the
      form of psychosis within families. The lifetime risk of schizophrenia in the
      first degree relatives of schizophrenic probands, and the risk of bipolar
      disorder in the first degree relatives of bipolar probands, were 5-10 times
      higher than reported population risks. Relatives of female and early onset (< 22
      years) schizophrenic probands had higher risk of schizophrenia than relatives of
      male and late onset schizophrenic probands. However, this effect was compensated
      in part by an excess of non-schizophrenic psychoses in the relatives of male
      probands. CONCLUSIONS: These results suggest a high familial, possibly genetic,
      loading in female and early onset schizophrenia, but do not resolve the question
      of heterogeneity within schizophrenia.

PMID- 7804661
TI  - Quantitative magnetic resonance imaging volumetry distinguishes delusional
      disorder from late-onset schizophrenia.
AB  - BACKGROUND: Late paraphrenia is recognised as a heterogeneous disorder. This is
      reflected by the division of such patients into schizophrenia and delusional
      disorder in ICD-10. Earlier imaging studies have suggested that major structural
      abnormalities may be associated with the onset of psychosis in later life.
      METHOD: Fifty late paraphrenics and 35 age-matched healthy controls underwent
      structural magnetic resonance imaging of the whole brain in the coronal plane.
      Measurements were made of intracranial and brain volumes and the volumes of the
      intracerebral and extracerebral cerebrospinal fluid spaces. RESULTS: No
      differences in intracranial, brain or extracerebral cerebrospinal fluid volumes
      between patients and controls were found. Late paraphrenic patients had greater
      lateral and third ventricle volumes than controls and the left lateral ventricle
      was larger than the right. When the patients were divided into appropriate ICD-10
      diagnoses: paranoid schizophrenia (n = 31) and delusional disorder (n = 16),
      lateral ventricle volumes in the delusional disorder patients were much greater
      than those of the schizophrenics and almost twice those of controls. CONCLUSIONS:
      Structural brain differences underly diagnostic heterogeneity within late
      paraphrenia. The brains of late onset schizophrenics are only subtly different
      from those of healthy elderly individuals.

PMID- 7804662
TI  - Proton magnetic resonance spectroscopy (1H MRS) of the hippocampal formation in
      schizophrenia: a pilot study.
AB  - BACKGROUND: Recent post-mortem and magnetic resonance imaging (MRI) studies
      strongly suggest a decrease in the volume of the hippocampus and other limbic
      temporal structures in schizophrenia. Therefore, we hypothesised that N-acetyl
      aspartate (NAA) which is found mainly in neurons and which can be measured by
      proton magnetic resonance spectroscopy (1H MRS) would be decreased in the limbic
      temporal region in schizophrenia. METHOD: Consenting subjects fulfilling DSM-III
      R criteria for schizophrenia (n = 11) and matched healthy volunteers (n = 11) who
      were recruited in a tertiary university referral centre, participated in a 1H MRS
      brain study. Proton MRS spectra were obtained from a 12 cm3 voxel (2 x 2 x 3 cm)
      in the right and left hippocampus/amygdala region. A researcher blind to the
      source of the spectra, measured the NAA intensity in all subjects, which were
      then statistically compared across the two groups. RESULTS: NAA intensities were
      significantly reduced in the right hippocampus/amygdala region of schizophrenic
      patients (P = 0.038). The difference of the left side did not reach significance
      at the 95% confidence level. CONCLUSIONS: The findings of decreased NAA in this
      study suggest that there may be a decrement in neuronal number or tissue volume
      of the right hippocampal/amygdala region in schizophrenia. Biochemical
      alterations in the metabolism of NAA in schizophrenia may be an alternative
      explanation. The findings are consistent with other types of post-mortem and in
      vivo evidence for hypoplasia of the limbic temporal structures in schizophrenia,
      postulated to be of neurodevelopmental pathogenesis.

PMID- 7804663
TI  - Predicting symptomatic and behavioural outcomes of community care.
AB  - BACKGROUND: Many studies of community care show little overall improvement in
      patient functioning. This study investigated whether cognitive impairment
      mediates the effect of the increased opportunities offered by the community.
      METHOD: Behaviour, symptoms, sociodemographic variables and information
      processing of a random sample of chronic psychiatric patients were examined. Six
      years later, social and behavioural outcomes were measured. RESULTS: The overall
      change in the group was negligible. Individual variation can be accounted for by
      two factors: time since transfer to the community, and initial information
      processing problems. Patients transferred for at least three years showed
      significant improvements. Schizophrenic patients without information processing
      problems improved, but those with deficits got worse. CONCLUSIONS: The
      identification of mediating factors should allow better rehabilitation plans, and
      alleviate the toxic effects that transfer has on some patients' functioning.

PMID- 7804664
TI  - Personality disorder in later life: a community study.
AB  - BACKGROUND: This exploratory study compares the prevalence of personality
      disorders and traits in people over and under 55 years of age. The comorbidity
      between personality and other psychiatric disorders is also examined. METHOD:
      Psychiatrists examined 810 subjects in a two-stage community survey. The semi
      structured Standardized Psychiatric Examination was used to diagnose all DSM-III
      personality disorders and other psychiatric disorders. RESULTS: The older
      subjects were significantly less likely than the younger subjects to have any
      personality disorder (6.6% v. 10.5%; relative odds = 0.42, 95% confidence
      interval = 0.25-0.70, P < 0.001). Antisocial and histrionic personality disorders
      were much less prevalent in the older than younger subjects (P < 0.05). The older
      subjects also had significantly fewer maladaptive personality traits (chi 2 =
      88.9, d.f. = 3, P < 0.001). The patterns of comorbidity between personality
      disorders and other psychiatric disorders were different in the two age groups.
      CONCLUSIONS: It is important to evaluate personality in patients of all ages.
      While some older patients no longer meet criteria for personality disorder,
      maladaptive traits may become evident during times of stress.

PMID- 7804665
TI  - A controlled psychiatric study of individuals at risk for Huntington's disease.
AB  - BACKGROUND: The study tested specific hypotheses that (a) there is an increased
      incidence of psychiatric disorders in asymptomatic heterozygotes for Huntington's
      disease (HD) compared with the normal homozygotes, and (b) there is an increased
      incidence of psychiatric disorders in the adult offspring of Huntington's disease
      patients compared with their partners. METHOD: A controlled study was made of 93
      apparently healthy individuals (at 50% risk), who had given DNA samples for the
      predictive test, and 70 of their partners. Current and past psychopathology was
      assessed and compared with the DNA predictive test results based on linkage
      analyses. The results of psychiatric assessments of the two groups were compared.
      RESULTS: DNA test results were available for 53 subjects (of 93). Five subjects
      at risk for HD were omitted from the study. The asymptomatic heterozygotes (n =
      20) showed no significant increase in the incidence of any psychiatric episode,
      depression, schizophrenia or behavioural disorder when compared with the normal
      homozygotes (n = 33). The whole tested group showed a significantly greater
      number of psychiatric episodes than their partners (n = 43). CONCLUSIONS:
      Asymptomatic HD gene carriers do not have a greater incidence of psychiatric
      disorders than the non-gene carriers born to a HD parent.

PMID- 7804666
TI  - Tiapride in the prevention of relapse in recently detoxified alcoholics.
AB  - BACKGROUND: The aim was to investigate the effect of tiapride (100 mg three times
      a day for at least one month) on outcome following detoxification. METHOD: The
      setting was a tertiary referral centre. The study design was randomised, double
      blind, and placebo-controlled. One hundred routinely admitted alcohol-dependent
      patients were entered, and 54 completed the trial. Outcome was assessed by
      considering drinking status at three months and six months follow-up, and by
      comparing psychological status at intake and follow-up using the Crown-Crisp
      Experiential index, the Litman Self-esteem scale and a Satisfaction with Life
      Situations scale. We also compared performance over the six months before
      admission with the three and six months of follow-up on measures of health,
      social and drinking variables. RESULTS: Tiapride proved better (usually at
      statistically highly significant levels) than placebo at promoting: abstinence,
      self-esteem, and satisfaction with life situations; and at reducing: alcohol
      consumption, use of health service resources, and levels of neuroticism.
      CONCLUSIONS: Tiapride merits serious consideration in the longer-term treatment
      of alcoholic patients.

PMID- 7804667
TI  - War trauma in a civilian population.
AB  - BACKGROUND: An epidemiological survey was made of war trauma and its consequences
      in the general population. METHOD: One member aged over 15 years from each of 101
      randomly selected families in a Primary Health Area in Sri Lanka were interviewed
      using the Stress Impact Questionnaire. RESULTS: Nearly one-half had experienced
      between five and nine war stresses, and one-quarter experienced over 10 (mean
      6.66). Only 6% had not experienced any. Sixty-four per cent had developed
      psychosocial sequelae, including somatisation (41%), post-traumatic stress
      disorder (27%), anxiety disorder (26%), major depression (25%), hostility (19%),
      relationship problems (13%), alcohol and drug misuse (15%) and functional
      disability (18%). CONCLUSION: The trauma experienced correlated strongly with
      psychosocial and somatic symptoms.

PMID- 7804668
TI  - Psychiatric disorders in a paediatric primary care clinic.
AB  - BACKGROUND: The proportion of children with psychiatric disorders treated in
      primary care is not known in most developing countries. METHOD: In a two-stage
      epidemiological study, 990 children aged between 7 and 14 years were screened
      with the parents' version of the Rutter scale. Of these, a stratified sample of
      227 was interviewed jointly with their mothers, using the children's version of
      the Schedule for Affective Disorders and Schizophrenia (K-SADS). RESULTS: We
      obtained a weighted prevalence of 19.6 +/- 2.5% for the presence of one or more
      DSM-III-R disorders. Depressive disorders were present in 6.0%, anxiety-related
      disorders in 4.7%, and conduct disorders in 6.1%. CONCLUSION: Psychiatric
      disorders in children are common in primary care. Doctors working at this level
      of care need the skills to detect and treat them.

PMID- 7804669
TI  - Psychiatric morbidity in primary health care in Santiago, Chile. Preliminary
      findings.
AB  - BACKGROUND: The aims were to determine the prevalence of psychiatric morbidity
      among primary care attenders in a poor suburb of Santiago and to study the
      relationship with health service use. METHOD: A cross-sectional survey was made
      of 163 consecutive attenders to a primary care clinic. RESULTS: Eleven per cent
      of the sample gave a psychological reason for consultation and the prevalence of
      psychiatric morbidity was 53%, defined using the revised Clinical Interview
      Schedule. Women and those of lower socio-economic status were at higher risk.
      Physicians recognised 14% of the psychiatric morbidity. Attenders with
      psychiatric morbidity consulted more frequently. CONCLUSIONS: There is a need to
      improve the recognition and management of psychiatric morbidity in primary care
      in Chile and other less developed countries. This could lead to the more
      efficient use of scarce health care resources in primary care.

PMID- 7804670
TI  - Affective disorders among elderly general practice patients. A two-phase survey
      in Brescia, Italy.
AB  - BACKGROUND: We investigated the prevalence of depression among 255 elderly
      general practice patients and the practitioners' performance in identifying
      depression. METHOD: Elderly patients attending 14 general practices entered a
      screening phase with GHQ-12 and MMSE. Those positive were then interviewed with
      GMS and HAS. RESULTS: DSM-III-R major depression affected 22.4%, dysthymic
      disorder 6.3%, not otherwise specified (n.o.s.) depression 7.1%. General
      practitioners performed fairly well: identification index 88.4%, accuracy 0.49,
      bias 1.85. CONCLUSIONS: Depression was markedly high. A selective progression of
      depressed elderly from the community to general practitioners is implied.

PMID- 7804671
TI  - Mental health problems of the Edinburgh 'roofless'.
AB  - BACKGROUND: The roofless have not been previously surveyed in detail looking
      specifically at their psychiatric status. METHOD: All roofless people in a
      discrete area were interviewed in their 'skippers' using a semi-structured
      interview. Other roofless people helped in case finding and diagnostic validity
      was confirmed using a computerised case register. RESULTS: Sixty-five people were
      interviewed. High rates of substance abuse (n = 48, 75%), and very low rates of
      psychotic illness (n = 2, 3%) were found. High rates of serious physical
      morbidity, of imprisonment and of being the victim of a crime were found.
      CONCLUSION: The roofless have multiple severe medical, social, and psychiatric
      problems. These all must be addressed when considering the provision of services.

PMID- 7804672
TI  - Suicide in Scotland 1988-1989. Psychiatric and physical morbidity according to
      primary care case notes.
AB  - BACKGROUND: The aim was to identify the amount of psychiatric and physical
      morbidity identified in suicide victims prior to death. METHOD: A survey was made
      of primary care records of Scottish suicide victims in the years 1988 and 1989.
      RESULTS: Less morbidity was encountered than in previous studies. Single persons
      and persons from lower socio-economic groups were less likely to have a diagnosis
      of depression. No association was found between physical and psychiatric
      morbidity. Depressed single persons and depressed persons from lower socio
      economic groups were less likely to receive antidepressants. GPs prescribed lower
      dosages of antidepressants than psychiatrists. Patients receiving antidepressants
      were more likely to die by drug overdose. CONCLUSIONS: There are groups in whom
      depression may be being overlooked and others in whom depression could be treated
      more vigorously. There are risks in prescribing antidepressants which are
      potentially fatal in overdose.

PMID- 7804673
TI  - A controlled evaluation of psychoeducational family intervention in a rural
      Chinese community.
AB  - BACKGROUND: The shortage of mental health care in rural China might be tackled by
      community care. This study tests the hypothesis that family intervention
      increases patients' treatment compliance, which is crucial in community care.
      METHOD: A cohort of psychiatric patients were randomly selected to a controlled
      trial for four months. Compliance rates, clinical and social outcomes were
      measured double-blindly. RESULTS: The compliance rate was increased significantly
      in the trial group, and they had better clinical and social outcomes.
      CONCLUSIONS: Family intervention is an effective method of improving treatment
      compliance and should be an important part of community mental health care.

PMID- 7804674
TI  - Lethal catatonia and neuroleptic malignant syndrome. A dopamine receptor shut
      down hypothesis.
AB  - BACKGROUND: Lethal catatonia and neuroleptic malignant syndrome (NMS) have been
      suggested to have a common neurochemical cause. We hypothesise that both
      conditions may be due to a sudden and massive blockade of dopamine
      neurotransmitters. METHOD: NMS was diagnosed in psychotic in-patients treated
      with neuroleptics if four features were present: diffuse severe rigidity, altered
      level of consciousness, hyperpyrexia and autonomic instability. RESULTS: Over
      three years, five NMS cases were diagnosed. Two presented with catatonic features
      and were diagnosed as acute reactive psychosis. Their neuroleptic doses were
      small, arguing for a particular sensitivity in these two cases. CONCLUSION: The
      sensitivity of two patients with catatonic features who developed NMS with small
      doses of neuroleptics supports a common neurochemical basis for the two
      conditions.

PMID- 7804675
TI  - Post-natal psychiatric morbidity.

PMID- 7804676
TI  - Head circumference at birth and schizophrenia.

PMID- 7804677
TI  - Lithium mutagenicity.

PMID- 7804678
TI  - Sinus bradycardia due to fluvoxamine overdose.

PMID- 7804679
TI  - Treatment of drug-induced anorgasmia.

PMID- 7804680
TI  - Violence in psychiatric units.

PMID- 7804681
TI  - Male erotomania and dangerousness.

PMID- 7804682
TI  - Cognitive function and fall-related fractures.

PMID- 7804683
TI  - Outdated ECT machines.

PMID- 7804684
TI  - Creativity and psychopathology.

PMID- 7804685
TI  - Lack of care in Rwanda.

PMID- 7804686
TI  - Cognitive therapy in panic disorder.

PMID- 7804687
TI  - Cross-cultural psychiatry.

PMID- 7804688
TI  - Treatment of hepatoma by liver transplantation.

PMID- 7804689
TI  - Single dose OKT3: adverse effects, pharmacokinetics, and anti-OKT3 antibody
      response.

PMID- 7804690
TI  - Renal transplantation in secondary amyloidosis.

PMID- 7804691
TI  - Donor mononuclear cell infusions as therapy for B-cell lymphoproliferative
      disorder following allogeneic bone marrow transplant.

PMID- 7804692
TI  - A complicated case of skin cancer in a renal allograft recipient.

PMID- 7804693
TI  - Kaposi's sarcoma in renal transplant recipients: a case report.

PMID- 7804694
TI  - The problem of cancer in organ transplant recipients: an overview.

PMID- 7804696
TI  - Skin cancer in renal transplant recipients.

PMID- 7804695
TI  - Secondary malignancies after marrow transplantation for leukemia or aplastic
      anemia.
AB  - We conclude that the most common secondary cancers which develop after marrow
      transplantation are lympho-proliferative disorders and solid tumors. The
      consequences of the secondary malignancies are serious, with more than 90% of the
      patients with non-Hodgkin lymphomas associated with EBV infection and more than
      75% of the patients with solid tumors dying despite treatment. Secondary leukemia
      developing in donor T-s is rare, but was fatal in all cases. EBV infection plays
      a major role in leading to the non-Hodgkin lymphomas in a setting of immune
      dysregulation from ATG or anti-T-cell monoclonal antibody treatment of acute
      GVHD. Other factors are also important for development of non-Hodgkin lymphoma
      and include T-cell depletion of donor marrow and HLA-mismatching between donor
      and recipient, known to lead to dysregulation of T-lymphocyte function. These
      factors set up an environment of proliferative stimuli which cannot be controlled
      by the recovering immune system, setting the stage for a secondary cancer. The
      role of irradiation is becoming more prominent in association with solid tumors,
      particularly in aplastic anemia patients conditioned with irradiation. The final
      event of tumor expression is most likely the result of a cascade of events,
      perhaps initiated with the conditioning regimen or with stimuli to proliferation,
      which, after later signals, leads to malignant transformation. For
      lymphoproliferative disorders, the time of latency is shorter than for solid
      tumors, suggesting a different molecular mechanism. The incidence of oncogene
      expression or mutation in tumor suppressor genes in these solid tumor patients
      has not been investigated.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7804697
TI  - Kaposi's sarcoma in renal transplant recipients.

PMID- 7804699
TI  - Carcinoma of the vulva in renal transplant patients.

PMID- 7804698
TI  - Recurrent lymphoma in a cardiac allograft recipient.

PMID- 7804701
TI  - Liver transplantation for primary and metastatic hepatic malignancies.

PMID- 7804702
TI  - Etiology and pathogenesis of tumors occurring after organ transplantation.

PMID- 7804703
TI  - Transmission of Kaposi's sarcoma by solid organ donation.

PMID- 7804704
TI  - [Current problems in the occupational medicine and industrial ecology (70 years
      of the Scientific Research Institute of Occupational Medicine of the Russian
      Academy of Medical Sciences)].

PMID- 7804705
TI  - [Development of rational work schedules for tunnel workers of schist mines].
AB  - The tunnelers of schist mines boring blast holes with hand drill are exposed to
      the discontinuous vibration and noise, which markedly exceed the MAL (12 and 11
      dB respectively). Though the time of exposure is reduced by mechanization, it
      exceeds the safe limits due to unequal shift load on the tunnelers team. The
      improved working schedule includes equal cyclic participation of every tunneler
      in the boring and limits the contact with vibration and noise. High risk of
      vibration disease in tunnelers even following the allowable time of contact with
      hazards can result from such confounding factors as cooling microclimate,
      intensive physical strain. The recommendations reduce the duration of employment
      to 7 years and necessitate mastering two allied occupations.

PMID- 7804706
TI  - [Clinical course of toxic dust-induced bronchitis in workers of electric furnaces
      for ferric chrome and silicone chrome melting].
AB  - Workers smelting sillcochrome and ferrochrome are likely to develop toxic and
      dust bronchitis besides the silicosis. The clinical syndromes present emphysema,
      asthma, inflammation, which is due to the chemical composition of the aerosol
      condensation. Toxic and dust bronchitis usually develop after 18 or more years of
      service.

PMID- 7804700
TI  - Epstein-Barr virus, infectious mononucleosis, and posttransplant
      lymphoproliferative disorders.
AB  - PTLD may be considered as an "opportunistic cancer" in which the immunodeficiency
      state of the host plays a key role in fostering the environment necessary for
      abnormal lymphoproliferation. The following discussion reflects our own current
      thoughts regarding events which may result in PTLD and its sequelae. Many of the
      individual steps have not been rigorously proved or disproved at this point in
      time. Following transplantation and iatrogenic immunosuppression, the host:EBV
      equilibrium is shifted in favor of the virus. Most seronegative patients will
      become infected either via the graft or through natural means; seropositive
      patients will begin to shed higher levels of virus and may become secondarily
      superinfected via the graft. There is a "grace" period of approximately one month
      posttransplant before increased viral shedding begins. PTLD is almost never seen
      during this interval. In many cases infection continues to be silent whereas in
      rare individuals there is an overwhelming polyclonal proliferation of infected B
      lymphocytes. This is the parallel of infectious mononucleosis occurring in
      patients with a congenital defect in virus handling (X-linked lymphoproliferative
      disorder). It is possible that transplant patients with this presentation also
      suffer a defect in virus handling. In other cases excessive iatrogenic
      immunosuppression may paralyze their ability to respond to the infection. With
      CsA and FK506 regimens, individual tumors may occur within a matter of months
      following transplant. The short time of incubation suggests that these are less
      than fully developed malignancies. It may be that local events conspire to allow
      outgrowth of limited numbers of B-lymphocyte clones. A cytokine environment
      favoring B-lymphocyte growth may be one factor and differential inhibition by the
      immuno-suppressive drugs of calcium-dependent and -independent B-cell stimulation
      may be another. In addition, there is some evidence that CsA itself may inhibit
      apoptosis within B cells. Since most patients do not develop PTLDs, an additional
      signal(s) for B-cell stimulation may be required. Indeed, it is possible that the
      virus may simply serve to lower the threshold for B-cell activation and/or
      provide a survival advantage to these cells. The ability of individual cell
      clones to evade a weakened immune system may set into play a Darwinian type of
      competition in which the most rapidly proliferating cells with the least number
      of antigenic targets predominate. In this regard, differences in host HLA types
      may determine the repertoire of viral antigens which are subject to
      attack.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7804707
TI  - [Comparative evaluation of fibrogenesis and toxicity of asbestos-containing heat
      proof materials].
AB  - The article deals with the results of studies analyzing the fibrogenic activity
      and toxicity of asbestos-containing heat insulators exemplified by asbestos
      board, vulcanite and asbestos vermiculite. Physical and chemical parameters of
      the studied dust are presented. All studied dust types have the distinct
      fibrogenic activity, the highest one was seen in asbestos board. The studied dust
      types could be classified according to the acute toxicity: asbestos board (DL50
      3.2 +/- 0.09 g/kg), chrysotile asbestos (DL50-2.0 +/- 0.08 g/kg), vulcanite (DL50
      1.9 +/- 0.08 g/kg) and asbestos vermiculite (DL50-0.7 +/- 0.04 g/kg). The article
      touches upon the probable acting mechanism of acute toxicity of asbestos and
      asbestos-containing dust.

PMID- 7804708
TI  - [Effect of ultra high frequency electromagnetic waves and lead on the workers'
      health; phytotherapy of the disorders].
AB  - The article deals with the study of combined exposure to ulta-high frequency
      electromagnetic waves and lead. Neurocirculatory asthenia was diagnosed in almost
      half of the examinees, cerebrovascular disorders, erythronormoblastic anemia and
      impaired porphyric metabolism were seen in some cases. Vegetable drugs improved
      the health status of examinees and corrected the changed parameters.

PMID- 7804709
TI  - [Comparative evaluation of maximum allowable exposure level of hazardous
      substances in the air of the working area established in China, Russia and USA].
AB  - The lists of American, Russian and Chinese MACs and TLV for chemical hazards in
      the air of workplace were analyzed. Chinese MACs turned out to be similar to
      Russian ones, because the definition of MAC and the methodic approaches to the
      parameter are equivalent. American TLV are not identical to MAC, therefore their
      values are different. The examples of difference in hygienic standards for
      various chemicals are given.

PMID- 7804710
TI  - [Rationale for maximum allowable exposure level of aluminum sulfate and its
      coagulants in the air of the workplace].
AB  - Aluminum sulfate, potash alum, ammonium alum, purified and unpurified nephelinic
      coagulant are assigned to the 3rd jeopardy class (moderately dangerous
      chemicals), sodium alum--to the 4th jeopardy class (slightly dangerous chemicals)
      at the single exposure. Local irritation of rabbit's skin was not revealed, but
      instillation into the eye results in conjunctivitis and purulent ophthalmitis.
      Aluminum sulfate and coagulants afflict the nervous system, liver and heart. The
      recommended MAC in the air of workplace for aluminum sulfate, potash alum, sodium
      alum and coagulants based on them is equal to 0.5 mg/m3.

PMID- 7804711
TI  - [Work conditions and health indicators in refrigeration workers].
AB  - The complex social and hygienic investigations helped to define occupational
      factors affecting the health of workers servicing the refrigerator railway
      wagons.

PMID- 7804712
TI  - [Effect of low intensity and ultra high frequency electromagnetic irradiation on
      memory functions].
AB  - The experiments on rats proved that low intensity electromagnetic waves result in
      retrograde amnesia due to benzodiazepine, gamma-aminobutyric acid and cholinergic
      mechanisms. Nootropic drug pyracethamum was proved to reduce the pathologic
      effect.

PMID- 7804713
TI  - [Health status of workers and employees of the "Electrozinc" plant exposed to
      hazardous chemical substances].
AB  - Present technology, sanitary equipment and hygienic measures in the main shops of
      "Electrozinc" plant are inadequate to prevent toxic pollution of environment.
      Climate and geographic position of Vladikavkaz city are also considered
      unfavourable. The air of "Electrozinc" working area and health status of
      "Electrozinc" employees were studied during past 5 years. Obtained results showed
      that employees engaged into lead and zinc production at "Electrozinc" are exposed
      to high concentrations of heavy elements (lead, zinc, cadmium et al.). Marked
      nonspecific biochemical changes as well as caused by specific exposure to lead
      and coexisting metals were detected in individuals, who had been considered
      apparently healthy. High level of transitory disablement morbidity also supports
      the idea of occupational hazards afflicting the health status of employees.
      Ecologic situation at "Electrozinc" and in Vladikavkaz necessitates further
      examination of health status in "Electrozinc" employees and inhabitants of nearby
      zone, treatment program and measures of primary prophylaxis.

PMID- 7804714
TI  - [Ethic problems in health status prognosis using genetic markers].
AB  - The mass genetic screening, which is repeatedly suggested for practical use,
      nowadays can be considered ineffective. The most complicated problem is genetic
      screening of workers. Low efficiency of such screening and limited possibilities
      to forecast the health status basing on the screening results are associated with
      the high probability of discrimination against workers according to their health
      status. Thus the genetic screening of workers should be forbidden as all
      employment medical examination except the cases when the diseases influence
      directly the ability to work.

PMID- 7804715
TI  - [Moral and ethic aspects of monitoring of individual susceptibility to
      occupational diseases].

PMID- 7804716
TI  - [Age-related functional characteristics of miners exposed to heat microclimate].
AB  - The article describes the functional changes with age in miners of deep coal
      mines in heating microclimate. The individuals of medium and senior age groups
      appeared to have significantly more frequent cardiovascular and thermoregulatory
      disorders than in the same age groups in normal climate. High temperature impairs
      autonomic nervous system, which presents hyperactivity of sympathicus and marked
      vegetative reactions in all ages, especially in the young workers.

PMID- 7804717
TI  - Immunological aspects of the effect of pentoxifylline (Trental) (a brief review).
AB  - Pentoxifylline (methixanthine derivate) has haemorheological activity, thought to
      based on its ability to reduce blood viscosity and increase the filterability of
      blood cells and widely used for the treatment of various types of vascular
      insufficiency. Recent studies provide evidence for the effect of this drug on
      immune functions. Pentoxifylline is able to influence in vitro as well as in vivo
      production of cytokine including tumour necrosis factor alpha. This drug has been
      shown to attenuate the symptoms of endotoxin shock and adult respiratory distress
      syndrome. Its beneficial effect on tumour-induced cachexia, organ transplantation
      and AIDS can widen the indications of clinical administration. Nevertheless, the
      chronic continuous administration of Pentoxifylline in arterial insufficiency is
      to be considered due to its potentially enhanced susceptibility to malignant
      disorders.

PMID- 7804718
TI  - Genotypic and phenotypic characters and nosocomial significance of bacteria
      endemic in neonatal intensive care units.
AB  - The degree of colonization was determined by complex typing (sero-, phage,
      colicin-, pyocin typing, plasmid profile analysis) of 212 Escherichia coli, 232
      Klebsiella, 117 Pseudomonas aeruginosa and 52 Staphylococcus aureus strains
      isolated from nose, throat, ear and other sources of 563 new-born infants in
      gynaecological and maternity wards of two neonatal intensive care units (NICU I
      and II) during a one year period. The presence of Klebsiella strains was more
      frequent in NICU I and E. coli and P. aeruginosa in NICU II, S. aureus occurred
      in a low level in both units. In NICU I 34 kinds, in NICU II 43 kinds of E. coli
      serotype were found. In NICU I the accumulation of serotypes O6:H-, O6:H1, O19:H
      , in NICU II O4:H-, O6:H1 was observed. The Klebsiella strains belonged in NICU I
      into 21, in NICU II into 12 phage types. Klebsiella was more frequent in NICU I
      than in NICU II, though the strains belonged to the same phage type in NICU II in
      50.7%, but in NICU I 4 frequent and 19 rare phage types occurred. Sero- and
      pyocin typing was effective for typing of P. aeruginosa. The most frequent sero-
      and pyocin types were in NICU I:O11a,11b; in NICU II: O2a,2d,2f; 12v. The rate of
      antibiotic resistance in E. coli, Klebsiella, P. aeruginosa and S. aureus was
      nearly the same in both units, multiple resistance was more frequent in NICU I
      (except P. aeruginosa, it was multiple resistant in 100% in both units). In NICU
      I 267, in NICU II 174 infants were treated with antibiotics. The administration
      of penicillin derivatives was nearly similar in the two care units and the
      resistance among E. coli and Klebsiella strains was nearly the same too. Though,
      cephalosporins were used more frequently in NICU II, resistance to cephalosporins
      among E. coli and Klebsiella was a bit higher in NICU I. Aminoglycosides were
      more often used in NICU I, resistance to aminoglycosides among E. coli and
      Klebsiella was higher in this unit. The rate of isolation of the examined
      bacteria was significantly lower in the group treated with antibiotics, than in
      the untreated group.

PMID- 7804720
TI  - Typing of coagulase-negative staphylococci isolated from immunocompromised
      patients.
AB  - A total of 3121 coagulase-negative staphylococcal strains sourced from clinical
      samples were characterized during a 4-year period. Biotype, antibiotic resistance
      pattern, phage pattern and slime production was determined. Plasmid profile
      analysis was performed on related isolates. Thirty percent of strains originated
      from the Bone Marrow Transplantation Unit, The National Institute of Haematology,
      Blood Transfusion and Immunology (NIHBTI), Budapest. Staphylococcus epidermidis
      occurred most frequently (48.8% in total, 58.2% source from NIHBTI). Total
      bacteriophage typability was 75.9%, and 603 phage patterns were observed. NIHBTI
      isolates differed in the incidence of multiply resistance, slime positivity and
      average frequency of phage patterns from the total suggesting spread of a
      selected hospital population. Statistical analysis of data obtained by typing
      showed no predominance of any endemic clone: the strains colonizing the
      immunocompromised patients and isolated from staff and inanimated environment
      differed from each other in biotype, phage pattern, antibiotic susceptibility,
      slime production and/or plasmid profile.

PMID- 7804719
TI  - The role of free radicals and antioxidative enzymes in erythrocytes and liver
      cells in the course of Plasmodium berghei and Plasmodium vinckei infection of
      mice.
AB  - Blood schisontocidal test of D0 + D3 type revealed different characteristics of
      the Plasmodium berghei and Plasmodium vinckei infection. Both types of the rodent
      plasmodia kill the untreated mice. Chloroquine treatment alone does not prevent
      the death of the P. berghei infected animals and they died at a low level of
      parasitaemia. The animals cured with chloroquine plus MAP survive. The infection
      with P. vinckei produces a high level of parasitaemia and the chloroquine
      treatment alone prevents the death of mice. The difference in the pathogenic
      characteristics between P. berghei and P. vinckei is manifested in the results
      measuring the kinetics of the activity of antioxidative enzymes in the red blood
      and liver cells of the infected mice: lipid peroxidation (LPO), superoxide
      dismutases (SOD), glutathione peroxidase (GP), catalase (CAT) and reduced
      glutathione (GSH). The rapid increase of the LPO in the RBC in particular in the
      P. vinckei infected animals indicates the prevailing role of the membrane
      detoxification process. A continuous increase in the activity of enzymes of
      cytoplasmic origin, e.g. SOD and GP was also observed. A powerful increase in GSH
      distinguishes the erythrocytes of P. vinckei infected animals. Similar but not
      identical data characterize the enzyme activities of the liver cells of the
      plasmodia infected animals.

PMID- 7804721
TI  - The effect of prostaglandins on the replication of adenovirus wild types and
      temperature-sensitive mutants.
AB  - Replication and transformation by adenoviruses involve their interaction with
      several cellular regulatory mechanisms. Alterations in the phosphorylation of
      both cellular and viral polypeptides by secondary messenger cAMP and cGMP
      dependent protein kinases (PK) determining outcome of viral effects may be
      influenced by external physiological stimuli, among them by prostaglandins (PG).
      HEp-2 cells infected with representative serotypes of human adenovirus (Ad)
      groups and two temperature sensitive (ts) mutants were treated prior to and late
      postinfection at permissive (32 degrees C) and restrictive (39 degrees C)
      temperatures by different PGs. PGF2 alpha augmented replication of both oncogenic
      Ad-12 and latent Ad-1, Ad-5 serotypes as well as Ad-5 mutants at 32 degrees C and
      that of mutant ts18 (defective in pVI phosphorylation) but not that of ts19
      (defective in pX phosphorylation) at 39 degrees C. PGE2 was shown to be
      inhibitory, but the replication of nononcogenic Ad-8 was not affected by PGs.
      PGI2 slightly enhanced all types, while indomethacin, inhibitor of endogenous PG
      synthesis with double unsaturated bonds moderately inhibited replication of all
      serotypes, except that of Ad-12. It is concluded that augmenting effects by PGF2
      alpha during viral entry, cytoplasmic transport and late phase, but not in the
      early phase of adenovirus replication cycle, are due to enhancement of the non
      specific cellular mechanisms, which support mitosis in the uninfected cells.
      Their activities are controlled by the late viral replication machinery, which
      process had been programmed in the early interaction of viral and cellular
      regulatory factors.

PMID- 7804722
TI  - Effectiveness of antibiotics on the autochthonous Escherichia coli of mice in the
      intestinal biofilm versus its planktonic phase.
AB  - The effectiveness of antibiotics was tested on the autochthonous Escherichia coli
      in biofilm mode of growth in large bowel pieces as well as on the predominant
      faecal E. coli isolated from the same SPF mice in planktonic phase of growth.
      Aminoglycoside antibiotics, chloramphenicol, oxytetracycline, erythromycin and
      lincomycin-clindamycin treatment had a very limited effect in the intestinal
      biofilm. Surprising ineffectiveness was found with polymyxins: polymyxin B showed
      a Minimal Bactericidal Dose of 0.78 microgram in planktonic phase, while it was
      400 micrograms for E. coli incorporated in the biofilm matrix. In contrast to the
      above groups of antibiotics, the beta-lactam drugs were effective both in the
      biofilm and in the planktonic phase growth of E. coli and their derivatives with
      broad or broader spectrum exerted an increased biofilm activity. Polymyxin B
      showed no sign of penetration into the colonic mucus, but on the other side
      ampicillin concentrated about three-four times in the intestinal matrix.

PMID- 7804723
TI  - Changes in the composition and peroxidation of yeast membrane lipids during
      ethanol stress.
AB  - Lipid peroxidation in Saccharomyces cerevisiae cells increased with ethanol
      treatment of the cells. Such cells have decreased amount of total lipid,
      phospholipid and free sterols. Sterol:phospholipid ratio decreased slightly in
      the cells treated with 4% ethanol. However, this ratio significantly increased
      with further rise in ethanol concentration to 12%. Relative content of
      glycolipids (glycolipid to phospholipid ratio) increased in ethanol-treated yeast
      cells. Diphosphatidylglycerol content increased significantly and
      phosphatidylcholine to phosphatidylethanolamine ratio decreased in ethanol
      treated cells. The amount of alpha-tocopherol decreased during ethanol stress.
      Catalase failed to counter the effect of ethanol. The results from the present
      study indicated that ethanol might be interfering with the antioxidant defence
      mechanisms of the yeast cells.

PMID- 7804724
TI  - Autologous activated lymphocyte therapy in a community hospital.
AB  - In the authors' institution patients suffering from metastatic melanoma, renal
      cell carcinoma or mesothelioma, resistant to conventional therapeutic modilities,
      are treated with adoptive immunotherapy. Tumour infiltrating lymphocytes (TIL)
      are prepared from surgical samples and expanded ex vivo in the presence of
      recombinant interleukin-2 (rIL-2). When sufficient amount of cells are available
      (5 x 10(9)-10(10)) they are being reinfused. The patients also receive rIL-2
      subcutaneously to support the activity and proliferation of reinfused TIL, and to
      avoid side effects caused by bolus or continuous intravenous administration.
      Leukapheresed lymphocytes activated by conditioned medium from OKT3 stimulated
      autologous lymphocytes and rIL-2 (autologous activated lymphocytes, AAL) are used
      as an alternative when TIL is not available or until it can be produced in
      sufficient amount. Subcutaneous IL-2 and oral cimetidine are also administered to
      support the reinfused AAL and to inhibit activation of CD8+ suppressor cells,
      respectively. Expression of activation markers CD25 and HLA-DR are monitored by
      flow cytometry as well as cytotoxicity is measured against K562 (NK specific
      target), HeLa (AALT specific) and against allogeneic or autologous tumour cell
      targets with a non-radioactive test. Methods are discussed by which the
      therapeutic efficiency of infused lymphocyte preparations can be improved.

PMID- 7804725
TI  - Is Escherichia coli ATCC 25922 a colicin producing strain? (a note).
AB  - The well-characterized strain of Escherichia coli ATCC 25922 recommended and
      widely used as a control Gram-negative bacterium for various laboratory
      experiments, especially for antibiotic susceptibility assays, was found to be
      antagonistic against another E. coli strain which is uniquely susceptible to
      fusidic acid, an antibiotic mainly active against Gram-positive bacteria. This
      antagonistic property appears to be selective, since it was not found against
      other E. coli or Staphylococcus aureus strains.

PMID- 7804726
TI  - Experimental accumulation of lead from soil through earthworms to common shrews.
AB  - Common shrews (Sorex araneus) were fed on earthworms containing high
      concentrations of lead. Both the earthworms and shrews originated from
      uncontaminated areas, but earthworms for the "lead" group of shrews were reared
      in the laboratory for 3 or 4 weeks in highly Pb-polluted soil from near an old
      lead smelter. The control group of shrews received the same amount of earthworms
      from the uncontaminated area. The acceptance of the experimental food by shrews
      was significantly lower in the lead group, indicating that the shrews were able
      to detect the lead in their food. After 2-31 days of feeding, the shrews in the
      lead group had significantly higher Pb concentrations in their liver, kidney,
      bone, and pelt than did the controls. Both the number of deaths during the
      experiment and the proportion of individuals with changes in kidney histology
      were significantly higher in the lead group.

PMID- 7804727
TI  - Effect of hydrogen on the pathway and products of PCB dechlorination.
AB  - The pathway and products of reductive dechlorination of 2,3,4-chlorobiphenyl by
      Hudson River sediment microorganisms were altered by H2. Under H2/CO2, 2,3,4-CBP
      was dechlorinated to 2,4-,2,3-, and then 2-CBP. On the other hand, under N2, the
      same organisms yielded only 2,4-CBP as they did under N2/CO2. Dechlorination was
      not inhibited by a single or periodic addition of a methanogenic inhibitor, 2
      bromoethanesulfonic acid under all gas atmospheres and thus, methane production
      was not necessary for dechlorination.

PMID- 7804728
TI  - Transport of acridine in saturated porous media.
AB  - The effects of the aqueous solution pH, temperature, initial solute concentration
      and non-equilibrium processes on the transport of acridine in saturated porous
      media (silica) were investigated in a series of continuous-flow column
      experiments. The enthalpy of the adsorption reaction was more exothermic when the
      solution pH was above acridine's pKa (5.6) than when it was below. The extent of
      adsorption was greater when the solution pH was below the pKa of acridine than
      when it was above. Non-equilibrium effects on the adsorption reaction were found
      to be unimportant at groundwater velocities. The results from this study suggest
      that the mobility of acridine in aquifers, in which adsorption to silica edge
      sites is significant, would increase as the temperature of the groundwater
      increased and the acridine mobility would be greatest when the pH of the
      groundwater is above the pKa of acridine. The transport of acridine in such
      aquifers can be effectively modeled using the local equilibrium assumption.

PMID- 7804729
TI  - Haemostatic function and arterial disease.
AB  - General recognition of the thrombotic component in ischaemic heart disease (IHD)
      is comparatively recent. Despite the obvious role of platelets, it has in many
      ways--and certainly epidemiologically--been work on the coagulation system that
      has been more rewarding in characterising those at high risk of IHD on account of
      haemostatic abnormalities. Raised plasma fibrinogen levels are clearly and
      independently associated with the onset of both clinically manifest IHD and
      stroke and probably with lower extremity arterial disease as well. High
      fibrinogen levels also increase recurrence rates and the progression of these
      conditions. High factor VII activity levels are associated with increased
      mortality from IHD but not with non-fatal episodes. Low fibrinolytic activity and
      raised factor VIII levels are also associated with increased IHD incidence. High
      fibrinogen levels predispose to thrombosis by effects on viscosity, platelet
      aggregability, fibrin deposition and the atherogenic process. There is increasing
      evidence that raised factor VII activity levels lead to increased thrombin
      production. Associations of several personal characteristics--notably smoking in
      the case of fibrinogen and dietary fat intake in the case of factor VII activity-
      influence the coagulation system in ways that are likely to predispose to
      thrombosis. Besides well known agents such as aspirin and anticoagulants,
      increasing attention ought now to be given to the antithrombotic potential of
      fibrinogen-lowering agents.

PMID- 7804730
TI  - Vessel wall interactions regulating thrombosis.
AB  - Endothelial cells are responsible for the secretion or surface expression of a
      wide variety of mediators involved in the control of thrombosis. These include
      von Willebrand factor, prostacyclin, nitric oxide, thrombomodulin, tissue-type
      plasminogen activator and its inhibitor, tissue factor and the tissue factor
      pathway inhibitor. The production of each of these can be modulated; in some
      cases very rapidly in response to external stimuli, in other cases more slowly.
      Thrombin is a key stimulus, which affects the production of almost all of these
      mediators. In addition, several cytokines and bacterial endotoxins shift the
      balance of endothelial mediator secretion from the basal anticoagulant profile
      towards a procoagulant profile.

PMID- 7804731
TI  - Pathology of arterial thrombosis.
AB  - The major cause of human arterial thrombosis is atherosclerosis. Thrombosis over
      atherosclerotic plaques is either due to superficial or to deep injury. In
      superficial injury there is endothelial denudation with thrombi adherent to the
      surface of the plaque. In deep injury more major plaque disruption exposes the
      lipid core to the lumen. Blood enters the core and thrombus forms within the
      plaque expanding its volume rapidly. Later thrombosis may, or may not, extend
      into the lumen leading to occlusion. Plaque disruptions heal by smooth muscle
      proliferation. Either form of thrombosis may occur in minor forms which invoke
      plaque growth alone or in major forms which precipitate clinical symptoms. In
      large arteries, such as the carotid, plaque disruption leads to chronic
      ulceration with exposed thrombus acting as a nidus for distal embolisation.
      Plaques with a high lipid and macrophage content in which smooth muscle cell
      numbers are low are at the greatest risk of disruption.

PMID- 7804732
TI  - Venous thrombogenesis.
AB  - Venous thrombosis develops when stasis in the deep veins of the legs occurs at
      times of increased coagulability of the blood. This combination leads to the
      local generation of thrombin, which is the crucial event in the pathogenesis of
      this disease. Impaired fibrinolysis allows a small platelet-fibrin nidus to grow
      into an occluding thrombus. Demonstrable damage to the vessel wall does not
      appear to play a major role in the development of most cases of venous
      thrombosis. While the biochemical definition of hypercoagulability remains
      elusive, immunoregulatory cytokines have been shown to impair the normal non
      thrombogenicity of the endothelial wall. This leads to local expression of
      procoagulant activity and resultant fibrin deposition. In the presence of stasis,
      the stage is then set for the development of clinically significant thrombi.
      Although hereditary absence of natural anticoagulants has been found in many
      patients with venous thrombosis, most patients have no detectable abnormality of
      their blood.

PMID- 7804733
TI  - Lipid-thrombosis interface.
AB  - Remnants produced on the lipolysis of triglyceride-rich lipoproteins provide a
      contact surface that activates the contact system of coagulation and therefrom
      factor VII. New evidence is reviewed suggesting that increased levels of
      circulating activated factor VII (VIIa) initiates coagulation and produces
      thrombin at higher rate at the site of an atheromatous lesion or at an injury
      site. This may have profound significance for the propagation of thrombus and for
      the thrombin-induced inflammatory and proliferative responses. Vascular
      homeostasis is achieved by the regulated interaction of the coagulation and
      fibrinolytic systems. An imbalance in this equilibrium may lead to an increased
      risk of thrombosis or a bleeding diathesis. The role of PAI-1, a potent inhibitor
      of enzymes that generate plasmin, in the regulation of fibrinolytic activity, is
      discussed and the evidence linking the expression of its activity to
      hypertriglyceridaemia is reviewed. Moreover, the association between lipoprotein
      (a) and coronary heart disease is attributed to its interference in the normal
      activation of plasminogen to plasmin.

PMID- 7804734
TI  - Molecular genetics of familial venous thrombosis.
AB  - Mutations in a variety of human genes are now known to predispose to venous
      thrombosis. Study of these mutations has led to important advances in our
      understanding of the structure and function of haemostatic regulatory proteins
      and has facilitated accurate presymptomatic and antenatal diagnosis. However,
      owing to the probabilistic nature of thromboembolism, only a certain proportion
      of patients with a recognized gene defect in the heterozygous state will actually
      suffer from thrombotic episodes. Allelic heterogeneity, epistatic effects
      resulting from the influence of other loci and environmental insults of various
      kinds all play a role in determining whether a thrombotic event occurs in
      individuals already compromised by a gene defect. Nevertheless, characterization
      of the wide spectrum of gene mutations giving rise to thrombosis may allow us to
      relate specific gene lesions to the probability of thromboembolism as well as to
      the severity and frequency of thrombotic episodes.

PMID- 7804735
TI  - Mechanisms, markers and management of coagulation activation.
AB  - Sensitive and specific laboratory methods are now available to detect and
      diagnose states of coagulation activation, defined as a procoagulant imbalance
      between the production and inhibition of enzymes in the coagulation system short
      of fibrin deposition. Although most coagulation enzymes cannot be measured
      specifically and accurately, assays for activated factor XII and factor VII have
      recently become available. Activated protein C, the active enzyme of a major
      anticoagulant pathway, can also be measured. Indirect approaches to the detection
      of coagulation activation are to measure the plasma levels of peptides released
      from coagulation zymogens when they are converted into active enzymes and the
      stable complexes formed in plasma when such enzymes are neutralized by their
      naturally-occurring inhibitors. These assay methods have dramatically improved
      our understanding of the mechanistic role of coagulation activation in health and
      disease. However, their clinical predictive value and usefulness for choosing and
      monitoring antithrombotic therapy still need to be defined in prospective
      clinical studies.

PMID- 7804736
TI  - Prevention and management of venous thrombosis.
AB  - Over the last 25 years, considerable progress has been made in the prevention,
      diagnosis and therapy of venous thromboembolism. The epidemiology of the disease
      has been investigated, defining patient groups at risk. Safe and effective
      methods of venous thrombosis prophylaxis have been evaluated in a wide range of
      patient populations, and recommendations for their application have been widely
      disseminated. Non-invasive techniques for the diagnosis of venous thrombosis and
      pulmonary embolism have been developed, and their capabilities and limitations
      have been defined. Guidelines for existing therapy have been refined, and new
      therapeutic agents have been introduced into clinical practice. A brief review of
      these is presented.

PMID- 7804737
TI  - Management of thrombosis in coronary heart disease.
AB  - Management of thrombosis in coronary heart disease comprises the management of
      acute coronary thrombosis presenting as myocardial infarction or as unstable
      angina, the use of anticoagulant therapy to prevent or treat complications of
      myocardial infarction, and prophylaxis in patients identified as being at
      increased risk. Thrombolytic therapy and aspirin independently and additively
      reduce mortality in evolving myocardial infarction. Aspirin and heparin, but not
      thombolytic agents, improve outcome in unstable angina. Heparin and warfarin
      reduce the risk of embolism from left ventricular thrombus forming post
      infarction. Aspirin has been shown to reduce the risk of further cardiovascular
      events or cardiac death in patients identified as at high risk. Current research
      is evaluating the role of antithrombins and platelet adhesion inhibitors as
      adjuvant therapy after thrombolysis, in unstable angina, and as heparin
      substitutes during coronary angioplasty, and of low dose warfarin as long-term
      prophylaxis in high risk patients.

PMID- 7804738
TI  - Management of thrombosis in stroke.
AB  - The management of thrombosis in stroke requires that several questions be
      answered concerning the diagnosis, aetiology, identification of problems, general
      and specific aspects of care, and prevention of further vascular events. Stroke
      is a clinical diagnosis, but cranial computed tomography (CT) scanning is
      required where there is diagnostic uncertainty or cerebral haemorrhage must be
      excluded. No specific medical therapies are of proven benefit in acute stroke but
      several large trials are currently evaluating promising antithrombotic therapies
      (antiplatelet, anticoagulant and thrombolytic agents). Aspirin has a proven role
      in the prevention of further vascular events after a stroke or transient
      ischaemic attack (TIA). In stroke and TIA patients with non-rheumatic atrial
      fibrillation, warfarin is highly effective at preventing recurrent events. The
      risk of recurrent stroke in patients with a symptomatic, severe carotid artery
      stenosis is greatly reduced by endarterectomy.

PMID- 7804739
TI  - Management of thrombosis in peripheral arterial disease.
AB  - There is accumulating evidence that thrombosis contributes to peripheral arterial
      disease, and that antithrombotic therapy should be considered at all symptomatic
      stages. In claudication, antiplatelet therapy is indicated in addition to
      lifestyle advice and sometimes surgery or angioplasty; the place of thrombolysis
      is unproven. In chronic critical limb ischaemia, prophylaxis of venous
      thromboembolism by low-dose heparin is indicated during hospitalisation, as is
      long-term antiplatelet therapy; local thrombolysis or systemic prostanoid
      infusions are increasingly used. In acute critical limb ischaemia, full dose
      heparinisation is followed by thromboembolectomy, local thrombolysis, angioplasty
      and surgery as appropriate. Antiplatelet therapy and/or anticoagulation are
      employed following such procedures, according to risk factors in the individual
      patient. Collaboration between vascular surgeons, radiologists and physicians is
      important in comprehensive patient care.

PMID- 7804740
TI  - Thrombin-induced endothelial cell dysfunction.
AB  - Endothelium is a multifunctional organ which can directly influence circulating
      blood components as well as other cells within the vessel wall. The clotting
      enzyme thrombin, generated at the surface of damaged endothelium, induces blood
      coagulation but also exerts a variety of functional effects on the endothelium
      itself. Thrombin acts on endothelial cells to stimulate synthesis and release of
      various agents, such as inflammatory mediators, vasoactive substances and growth
      factors. It causes leukocyte adhesion to the endothelium by triggering expression
      of adhesion molecules on the cell surface and causes disruption of endothelial
      permeability properties. The majority of thrombin effects on endothelial cells
      are mediated by its receptor and require its lytic activity. Differences have
      been observed among the response to thrombin of endothelial cells of different
      origin. In general microvascular endothelial cells appear to be particularly
      sensitive to this enzyme. Thrombin induced microvascular dysfunction can have
      pathological consequences and contribute to organ reactions to inflammation and
      ischaemia.

PMID- 7804741
TI  - Primary and secondary prevention of arterial thromboembolism.
AB  - Aspirin in doses of approximately 300 mg/day may be recommended for the primary
      prevention of myocardial infarction in males and probably also in females, but
      only in those individuals with a moderate to high risk of cardiovascular disease.
      In patients with stable angina, aspirin decreases the risk for a first myocardial
      infarction. Aspirin or ticlopidine should be given to patients with unstable
      angina, in conjunction with heparin in the most severe cases. Long-term oral
      anticoagulant treatment after myocardial infarction in low risk patients has a
      limited effect on mortality but reduces the incidence of non-fatal recurrent
      myocardial infarction and stroke. Daily aspirin is more convenient and simple,
      and is at least as effective, but associated with a lower risk of bleeding. The
      concurrent use of aspirin and low intensity anticoagulation in the secondary
      prevention of myocardial infarction has, however, not been investigated. Various
      antiplatelet agents, including aspirin (alone or combined with dipyridamole) and
      ticlopidine, have, in contrast to oral anticoagulants, proved useful in the
      prevention of early thrombosis in aorto-coronary grafts, provided treatment
      begins at the latest 6 h after surgery. The usefulness of antiplatelet drugs has
      been well established in the prevention of immediate reocclusion following
      coronary angioplasty, but so far no drugs can prevent late restenosis. In
      patients with a synthetic cardiac valve prosthesis, lifelong treatment with
      coumarins is still indispensable, but their antithrombotic effect can be
      reinforced by dipyridamole or aspirin which also allows to reduce the intensity
      of anticoagulation. In uncomplicated bioprosthetic valve replacement, low
      intensity anticoagulation during the first 3 months suffices. Diuretics probably
      provide the best primary protection against cerebrovascular accidents in moderate
      hypertensives, although medium doses of aspirin may be considered in elderly
      people at high risk of such accidents. Aspirin (alone or combined with
      dipyridamole) and ticlopidine may be recommended for the secondary prevention of
      cerebral ischaemic accidents. Aspirin and ticlopidine, but not oral
      anticoagulants, reinforce the treatment of obliterative arterial disease in the
      lower limbs.

PMID- 7804742
TI  - Thrombosis on foreign surfaces.
AB  - The increasing use of biomaterials in blood-contacting applications underlines
      the importance of an enhanced understanding of the interactions of blood with
      foreign surfaces. These interactions constitute a complex response involving the
      possible participation of proteins, platelets, the intrinsic coagulation, the
      fibrinolytic system, erythrocytes, leucocytes and the complement system.
      Interpretation of blood-biomaterial interactions and the development of improved
      biomaterials require the utilisation of in vitro, ex vivo or in vivo blood
      compatibility assessment procedures, although there is no ideal procedure for
      linking assessment to the potential clinical performance of a material. In
      clinical application, foreign surfaces represent only one of the factors
      influencing the blood response, with the response also influenced by the presence
      of antithrombotic agents, the blood condition and the nature of the application.

PMID- 7804743
TI  - Molecular cell biology and physiology of solute transport.

PMID- 7804744
TI  - Pharmacology and therapeutics.

PMID- 7804745
TI  - Kinins and the vascular actions of converting enzyme inhibitors.

PMID- 7804746
TI  - Epithelial sodium channels.
AB  - The highly selective amiloride-sensitive epithelial sodium channel is expressed
      in the distal part of the nephron, the distal colon, and the lung. It plays a
      critical role in the control of sodium balance, extracellular volume, blood
      pressure, and of fluid reabsorption in the lung. The primary structure of the rat
      epithelial sodium channel has recently been determined. It is a heteromultimeric
      protein made up of three homologous subunits (alpha, beta, and gamma). The
      biophysical properties, the cell distribution, and the regulation of this channel
      will be reviewed, with emphasis on its expression in the kidney, colon, and lung,
      where the clinical implications are most relevant. The epithelial sodium channel
      is a member of a novel gene superfamily that encodes cation channels involved in
      the control of cellular and extracellular volume and in the control of distinct
      functions such as taste transduction and mechanotransduction.

PMID- 7804747
TI  - Calcium channels.
AB  - A key step in renal calcium reabsorption is dihydropyridine-sensitive calcium
      entry across the apical membrane of the distal tubule. Electrophysiologic studies
      have confirmed the existence of calcium channels that may mediate this pathway.
      Molecular studies of voltage-dependent calcium channels have revealed a
      surprising degree of heterogeneity. The pore-forming alpha 1 subunit is encoded
      by multiple genes, each directing the synthesis of several alternatively spliced
      transcripts whose products may in turn be posttranslationally cleaved to yield
      multiple differently-sized peptides. Further heterogeneity is afforded by the
      presence of accessory subunits, such as the beta subunit, which is also encoded
      by a multigene family. Site-directed mutagenesis studies of the alpha 1 subunit
      have begun to explore the molecular structure of the calcium pore. Molecular
      cloning of rat renal calcium channel transcripts has identified alpha 1 and beta
      subunit genes that are expressed in the distal tubule. Future studies will
      address the structure-function relationship of various physiologic properties
      associated with the channels expressed by these genes.

PMID- 7804748
TI  - Renal sodium-phosphate cotransport.
AB  - Proximal tubular reabsorption of inorganic phosphate (P(i) is a major determinant
      of the extracellular concentration of phosphate. The net proximal reabsorption of
      phosphate largely depends on the rate of apical sodium-dependent transport of
      P(i) (Na/P(i) cotransport), which is controlled by various hormonal and
      nonhormonal factors. Renal Na/P(i) cotransport systems that represent proximal
      apical Na/P(i) cotransport systems have recently been identified. Molecular
      knowledge of proximal tubular Na/P(i) cotransport will lead to a new
      understanding of the cellular mechanisms of the physiologic control of proximal
      P(i) reabsorption and to elucidation of the pathophysiologic mechanisms impairing
      P(i) homeostasis.

PMID- 7804749
TI  - Erythrocyte sodium-lithium countertransport: another link between essential
      hypertension and diabetes.
AB  - Erythrocyte Na+/Li+ countertransport has been extensively investigated in human
      essential hypertension in numerous clinical, epidemiologic, and genetic studies
      and through these studies has emerged as the best-characterized intermediate
      phenotype. Patients with elevated antiporter activity manifest high total body
      exhangeable Na+ levels, renal and cardiac hypertrophy, and metabolic
      abnormalities which are part of the syndrome characterized by resistance to
      insulin-stimulated body glucose disposal. The coexistence of hypertension with
      insulin resistance and elevated Na+/Li+ countertransport has suggested that a
      link between the metabolic and ion transport abnormalities may be mediated
      through elevated insulin levels. In vitro studies in erythrocytes of fasted
      individuals have demonstrated that physiologic doses of insulin increased the
      maximal transport rate and the concentration for half-maximal transport for Na+
      of both the Na+/Li+ and Na+/H+ exchanges. In vivo, Na+/Li+ exchange also exhibits
      a low affinity for Na+ in insulin-resistant hypertensive patients and in patients
      with insulin-dependent diabetes mellitus complicated by nephropathy. Insulin
      modulation of this antiporter may play a role in the chronic alterations in Na+
      homeostasis observed in hypertension and diabetes.

PMID- 7804750
TI  - Mesangial cell ion transport and tubuloglomerular feedback.
AB  - Mesangial cells possess Ca(2+)-activated Cl- channels, Ca(2+)-activated K+
      channels, voltage-gated Ca2+ channels, ATP-sensitive K+ channels, and two types
      of nonselective cation channels. Angiotensin II and arginine vasopressin
      depolarize the membrane. This membrane depolarization is caused by the activation
      of Ca(2+)-activated Cl- and Ca(2+)-activated nonselective cation channels through
      an elevation of intracellular Ca2+ concentration. The Ca(2+)-independent
      nonselective cation channel is activated by platelet-derived growth factor and is
      a candidate for the receptor-activated Ca2+ influx system. It has been suggested
      that macula densa Cl- reabsorption determines the Cl- concentration of
      juxtaglomerular apparatus interstitial fluid and thereby affects the resistance
      of afferent arterioles. In addition, angiotensin II-mediated and arginine
      vasopressin-mediated mesangial cell Ca2+ signals and contraction are attenuated
      via prostaglandin production by the mesangial cells themselves when the ambient
      Cl- concentration is reduced. Thus, Cl- plays an essential role in the
      tubuloglomerular feedback mechanism. The intracellular Ca2+ concentration appears
      to be important for the signal transduction mechanism of tubuloglomerular
      feedback. The ionic channels on the mesangial cell membrane may participate in
      controlling the intracellular Ca2+ concentration. The association of disturbed
      tubuloglomerular feedback and the development of hypertension has recently been
      reported.

PMID- 7804751
TI  - Crosstalk and epithelial ion transport.
AB  - Coordination of ion transport through channels, pumps, exchangers, and
      cotransporters (or crosstalk) is essential in preserving homeostasis of cell
      volume and ionic activities while maintaining an adapted response to fluctuations
      in hormonal and environmental challenges. Crosstalk in epithelia is a concerted
      action of multiple cytosolic and membrane-bound ion transport regulators. Some of
      the most likely candidates as crosstalk signals include Ca2+, pH, G protein,
      actin filaments, protein kinases, ATP, and membrane shuttling. An integrated view
      of the interaction and convergence of multiple signal pathways on single ion
      channels is one of the major challenges in membrane transport physiology.
      Simultaneous measurements of changes in the activity of putative signals and of
      ion transport rates at the macroscopic and single channel level provide insights
      into crosstalk phenomena. This measurement is made possible by combining short
      circuit current and single channel patch-clamp recording with single cell
      spectrofluorescence in intact epithelia. In a wide range of Na(+)-absorbing
      epithelia, there is evidence that small variations in intracellular pH and Ca2+
      can simultaneously regulate the activity of Na+ and K+ channels. Crosstalk
      between the Na/K pump and K+ transport may be mediated by physiologically
      relevant changes in the ratio ATP:ADP.

PMID- 7804752
TI  - Angiotensin II receptor antagonists and the kidney.
AB  - The kidney is not only the source of circulating renin, which determines the
      plasma concentration of angiotensin II, but it is also one of the main targets of
      angiotensin II. Thus, angiotensin II exerts an important physiologic influence on
      renal function through its ability to modulate renal hemodynamics as well as
      glomerular and tubular functions. Moreover, angiotensin II appears to contribute
      to the progressive deterioration of renal function commonly observed in renal
      diseases. The availability of new orally active, nonpeptide angiotensin II
      receptor antagonists lacking agonistic or kinin- and prostaglandin-inducing
      properties has offered the possibility of investigating further the renal
      influence of angiotensin II. Thus, it is now clear that most if not all renal
      effects of angiotensin II are mediated by the activation of AT1 receptors,
      although the AT2 subtype is present in the kidney. Furthermore, increasing
      experimental evidence indicates that the long-term renal protective effect of
      angiotensin-converting enzyme inhibitors is indeed due to the inhibition of the
      renin-angiotensin system rather than to the activation of non-angiotensin II
      mechanisms.

PMID- 7804753
TI  - Obesity and hypertension.
AB  - An increasing number of clinical trials have demonstrated that obese patients are
      more likely than lean individuals to be hypertensive. Moreover, both obesity and
      arterial hypertension have been identified as independent risk factors for
      cardiovascular disease. Pathophysiologically, obesity appears to have a major
      influence on the hemodynamic changes associated with hypertension. The available
      evidence suggests that at any given level of arterial pressure, obese
      hypertensive patients have a higher cardiac output and lower total peripheral
      resistance than do lean patients. Recent reports have indicated that obesity
      exerts a disparate effect on target organs in hypertension. Whereas at rest
      obesity seems to mitigate cardiovascular changes in the systemic vascular bed
      caused by hypertension, no such mitigation was observed in the renovasculature;
      left ventricular hypertrophy as a major cardiovascular risk factor was even
      exacerbated by the presence of obesity. The different hemodynamic patterns in
      obese hypertensive patients have recently been shown clinically relevant for
      treating hypertensive patients.

PMID- 7804754
TI  - Mineralocorticoids and blood pressure.
AB  - Recent observations suggest that the syndrome of mineralocorticoid excess,
      primary aldosteronism, may be more common than has been previously believed.
      Enhanced detection of this syndrome has been simplified by the development of
      sensitive screening techniques. The diagnosis and differentiation of several
      different forms of primary aldosteronism have also been improved by new insights
      into the pathophysiology of these disorders and the application of several new
      techniques to distinguish them. The discovery of variable activity of several
      steroids on the mineralocorticoid receptor has provided additional understanding
      of the finding of the manifestations of hyperaldosteronism in the presence of
      normal aldosterone production. Finally, new approaches to the treatment of
      primary aldosteronism have also been developed.

PMID- 7804755
TI  - Kidney disease and hypertension in blacks.
AB  - Black Americans have relatively more hypertension and hypertensive renal disease
      than white Americans. The reasons for these differences are not clear and are
      under investigation. The genetic basis of hypertension may be different between
      blacks and whites. The response to systemic hypertension may also be different.
      Hypertensive black patients appear to develop renal arterial fibroplasia and
      renal insufficiency at an earlier age than white patients. Adequate control of
      blood pressure appears to be more effective in slowing the rate of decline in
      renal function among whites than among blacks. However, the available data are
      not sufficient. More information is needed to identify risk factors for the
      development of end-stage renal disease and to guide the management of
      hypertension in blacks.

PMID- 7804756
TI  - Microalbuminuria.
AB  - Microalbuminuria indicates slightly elevated urinary albumin excretion. In most
      cases, microalbuminuria is of glomerular origin and indicates initial
      glomerulosclerosis. Microalbuminuria has a high predictive value for nephropathy
      in insulin-dependent diabetes subjects and for premature mortality due to
      cardiovascular disease in non-insulin-dependent diabetes subjects and in the
      general population. All cardiovascular risk factors can be determinants for
      microalbuminuria constitution, especially the genetic determinants of these risk
      factors. Thus, microalbuminuria can be an indicator to summarize renal or
      cardiovascular risk, or both, in various populations. Treatment interventions
      were performed using microalbuminuria as the endpoint. So far, the most
      convincing results were obtained with angiotensin I-converting enzyme inhibitors
      to prevent nephropathy in insulin-dependent diabetes subjects.

PMID- 7804758
TI  - Sexual abuse of children. A selected bibliography.

PMID- 7804757
TI  - Assessment of renal function and progression of disease.
AB  - Detection of early renal dysfunction remains a difficult problem because
      creatinine levels often do not become abnormal until glomerular filtration rate
      is severely reduced. Creatol, which also accumulates in renal failure, has been
      suggested as an alternative to creatinine. To measure glomerular filtration rate,
      a number of simplified techniques have been suggested; for the most part,
      however, they have not been validated in patients with severe chronic renal
      failure. Glomerular filtration rate can be estimated with fair precision from
      serum creatinine concentration with the use of improved equations, provided that
      the serum creatinine level is greater than 2 mg/dL. The use of cimetidine to
      reduce the discrepancy between creatinine clearance and glomerular filtration
      rate does not seem justifiable. In diabetic nephropathy, sequential biopsies may
      be preferable to sequential determinations of glomerular filtration rate for
      follow-up of patients with this disease.

PMID- 7804759
TI  - Doing justice and doing good: conflicts for mental health professionals.
AB  - The primary role of mental health professionals in cases of child abuse should be
      to treat the victims and the offenders. Currently, however, mental health
      professionals are often involved in the investigation and adjudication of child
      sexual abuse claims. This article discusses the conceptual and practical
      conflicts this involvement creates with the mental health professional's
      therapeutic role. The author concludes that mental health professionals should
      not be involved in investigating child sexual abuse cases. Furthermore, he
      contends that mental health testimony about the victim should never be allowed
      during the adjudication stage and that mental health testimony about the
      defendant should be allowed only if the defendant puts his character into
      question. The scientific knowledge base for such testimony is very limited, and
      the testimony is likely to be more misleading and prejudicial than helpful.
      Mental health professionals, however, could appropriately help children and
      adults prepare for legal proceedings and facilitate mediation.

PMID- 7804761
TI  - Responding to child sexual abuse: the need for a balanced approach.
AB  - This article suggests a number of improvements in the reporting and investigation
      of child sexual abuse cases. The article begins with a reminder that our
      eagerness to protect children cannot be allowed to overcome our nation's
      commitment to fairness and due process. For both the alleged perpetrator and the
      child victim, much is at stake in these cases, and our system must strike a
      balance to protect the rights of both. Currently there is a problem with both
      underreporting of suspicions of child abuse and overreporting of cases that are
      unfounded or cannot be substantiated. Several recommendations are made to make
      reporting more accurate. These include: clarify reporting laws, expand and
      improve training for reporters, develop agency policies regarding reporting,
      modify liability and immunity rules, improve efforts at screening reports, and
      provide feedback to reporters. Finally, the article discusses the importance of
      interviewing children and offers some techniques for doing so properly. Issues of
      interpreting physical and behavioral signs of abuse are also discussed, and the
      importance of accurate record keeping is emphasized.

PMID- 7804760
TI  - The role of physicians in reporting and evaluating child sexual abuse cases.
AB  - Physicians become involved in child sexual abuse when they must report suspected
      abuse or when they are asked to medically evaluate a child who is an alleged
      victim of abuse. This article reviews recent progress in the medical profession's
      attention to child sexual abuse and discusses current issues surrounding
      reporting and medical evaluation. The reporting requirement raises several
      concerns for pediatricians. Their legal responsibilities as reporters may
      conflict with their traditional relationship with the family as a unit and with
      the confidentiality of the doctor-patient relationship. Knowledge about pediatric
      anogential anatomy is in a relatively early stage of development, and few
      pediatricians receive training adequate to enable them to determine whether
      medical observations are consistent with sexual abuse. Even fewer pediatricians
      receive training in the unique considerations and needs present when taking the
      medical history of a possible abuse victim or when preserving evidence for
      possible later use in court. The medical evidentiary evaluation of suspected
      sexual abuse also raises a number of concerns. There is great variability in
      referral patterns, which determine whether a medical examination will be
      requested and whether a general practice physician or a specialist will be asked
      to conduct the exam. Although professional medical associations have laid out
      broad outlines of recommended procedures for medical exams when sexual abuse is
      suspected, more detailed protocols are needed for addressing the many cases where
      findings are ambiguous or subtle. Often physicians need training in forensics and
      assistance in coordinating services with multiple agencies and professions.
      Finally, attention must be given to ensuring adequate cost reimbursement for
      medical evaluations.

PMID- 7804762
TI  - Efficacy of treatment for victims of child sexual abuse.
AB  - It is common practice to recommend psychotherapy for children who have
      experienced sexual abuse. However, there is no agreed-upon means by which to
      assess the needs of these children or to determine the nature of the treatments
      to be offered. Most existing research bearing on these issues consists of
      descriptive data, pre- and postanalysis, and correlation studies of mixed and
      nonstandardized treatments. This research suggests that the rate of spontaneous
      recovery following disclosure of sexual abuse is high, but that both a need and a
      benefit exist for the provision of support during the acute adjustment period for
      those children who are most at risk for long-term negative effects. The authors
      contend that the event of sexual abuse does not, in and of itself, create a need
      for treatment in all child victims. They recommend comprehensive assessments to
      determine which children are at risk for subsequent problems, the extrapolation
      of findings from other research domains to individualize treatment, and the use
      of empirically validated interventions.

PMID- 7804763
TI  - Offenders: characteristics and treatment.
AB  - People who sexually abuse children are diverse in terms of age, occupation,
      income level, marital status, and ethnic group. At one time it was believed that
      sex offenders could be easily categorized along three dimensions: offending
      against either adults or children; offending against either members of their
      families or against acquaintances and strangers; offending in noncontact ways
      (for example, exhibitionism) or through bodily contact. There is growing evidence
      that a number of offenders offend across these categories. Many child sexual
      abusers are themselves adolescents, and many adult offenders first offended when
      they were adolescents. A review of the literature reveals a paucity of controlled
      therapy outcome studies on the effectiveness of treatment, and existing
      uncontrolled studies are marked by methodological problems. This has led some to
      conclude that there is insufficient evidence to prove the effectiveness of
      treatment for child molesters. However, there have been major changes in
      treatment programs over the years, and some more recent studies provide reason
      for optimism about the effectiveness of current treatment methods for some
      offenders.

PMID- 7804764
TI  - Prevention of child sexual abuse.
AB  - Efforts to prevent child sexual abuse have taken a distinctly different path from
      efforts to prevent the physical abuse of children. Currently, child sexual abuse
      prevention is virtually synonymous with group-based instruction for children on
      personal safety, and it appears that most schools and many after-school programs
      provide some form of group-based sexual abuse prevention education. Many
      evaluations have assessed the impact of these efforts. Seventeen studies
      employing random assignment to treatment and control groups are summarized in
      Table 1 on page 206, and 21 additional studies using quasi-experimental designs
      are briefly reviewed in the article text. Most studies conclude that children do
      learn from the experience, although such learning is neither universal nor
      comprehensive. Most evaluations measure the child's knowledge but are unable to
      assess whether a gain in knowledge will lead to a sustained beneficial change in
      the child's behavior. In an effort to focus on behavior change, child safety
      programs increasingly utilize role playing and participant modeling. A major
      benefit of personal safety education programs may be an increased rate of
      disclosures by children of past or present abuse. A major area of concern may be
      the potential for safety education programs to engender fear and anxiety in
      children Research on negative impacts is limited, and results have been mixed.
      The author concludes that prevention programs overall have beneficial impacts,
      which are strongest for children 7 to 12 years old. Characteristics of promising
      programs are summarized. The article concludes with suggestions for expanding
      prevention efforts to include public and parent education, life skills training
      for young adults, support groups for vulnerable children and adults, and
      intervention for identified victims and perpetrators.

PMID- 7804765
TI  - Child sexual abuse: awareness and backlash.
AB  - This article reviews the historical development of awareness about child sexual
      abuse and the counterreaction that this increasing awareness has often triggered.
      In particular, Conte discusses the current backlash against awareness of child
      sexual abuse, a reaction that he describes as characterized by extreme positions
      with lack of supporting data and near total rejection of knowledge and
      experiences of child sexual abuse. He urges all those who work professionally in
      the area of child sexual abuse to ensure that their opinions and actions are
      based on sound research and directed toward improving the lives of abused
      children.

PMID- 7804766
TI  - Reported child abuse and neglect.

PMID- 7804767
TI  - Home visiting.

PMID- 7804768
TI  - Current information on the scope and nature of child sexual abuse.
AB  - Approximately 150,000 confirmed cases of child sexual abuse were reported to
      child welfare authorities in the United States during 1993. This number
      represents about 15% of the more than one million confirmed cases of all child
      abuse and neglect. But the true scope of this problem is better reflected in
      retrospective surveys of adults, and this article summarizes data from 19 of
      these surveys. Considerable evidence exists to show that at least 20% of American
      women and 5% to 10% of American men experienced some form of sexual abuse as
      children. The rates are somewhat lower among people born before World War II, but
      there is little evidence of a dramatic increase for recent generations. The
      studies provide little evidence that race or socioeconomic circumstances are
      major risk factors. They do show elevated risk for children who experienced
      parental inadequacy, unavailability, conflict, harsh punishment, and emotional
      deprivation. Adult retrospective studies are also good sources of information
      about the characteristics of abuse. Most sexual abuse is committed by men (90%)
      and by persons known to the child (70% to 90%), with family members constituting
      one-third to one-half of the perpetrators against girls and 10% to 20% of the
      perpetrators against boys. Family members constitute a higher percentage of the
      perpetrators in child protective agency cases because the mandate of these
      agencies generally precludes their involvement in extrafamily abuse. Around 20%
      to 25% of child sexual abuse cases involve penetration or oral-genital contact.
      The peak age of vulnerability is between 7 and 13. Studies of the criminal
      justice processing of sexual abusers suggest that, compared with other violent
      criminals, slightly fewer are prosecuted, but of those prosecuted, slightly more
      are convicted. Studies conducted in the 1980s also showed that, once convicted,
      relatively few sexual abusers receive sentences longer than one year, while 32%
      to 46% serve no jail time. Overall, there is little evidence to suggest that
      either the child welfare system or the criminal justice system abandons its usual
      standards of operation and acts hysterically when confronted with sexual abuse.

PMID- 7804769
TI  - Sexual abuse of children: recommendations and analysis.

PMID- 7804771
TI  - Reporting and investigating child sexual abuse.
AB  - This article describes the process for reporting and investigating child sexual
      abuse cases. Reporting mandates are discussed, as well as several concerns and
      criticisms about how these are implemented. The article also discusses a number
      of key issues related to the investigation of claims. The authors recommend
      greater use of multidisciplinary investigative teams and the development of
      comprehensive investigative protocols. Specific controversies, such as those
      concerning the use of video-taping, anatomical dolls, and validation tests, are
      also addressed.

PMID- 7804770
TI  - Immediate and long-term impacts of child sexual abuse.
AB  - Research conducted over the past decade indicates that a wide range of
      psychological and interpersonal problems are more prevalent among those who have
      been sexually abused than among individuals with no such experiences. Although a
      definitive causal relationship between such difficulties and sexual abuse cannot
      be established using current retrospective research methodologies, the aggregate
      of consistent findings in this literature has led many to conclude that childhood
      sexual abuse is a major risk factor for a variety of problems. This article
      summarizes what is currently known about these potential impacts of child sexual
      abuse. The various problems and symptoms described in the literature on child
      sexual abuse are reviewed in a series of broad categories including posttraumatic
      stress, cognitive distortions, emotional pain, avoidance, an impaired sense of
      self, and interpersonal difficulties. Research has demonstrated that the extent
      to which a given individual manifests abuse-related distress is a function of an
      undetermined number of abuse-specific variables, as well as individual and
      environmental factors that existed prior to, or occurred subsequent to, the
      incidents of sexual abuse.

PMID- 7804772
TI  - Adjudication of child sexual abuse cases.
AB  - This article discusses issues in the adjudication of child sexual abuse
      allegations. Such allegations may be tried in criminal court and/or civil court
      (in child abuse or divorce proceedings), and these forums are discussed. Often
      central to any of these proceedings is the necessity for a child to testify. The
      article reviews research about the believability of child witnesses and discusses
      accommodations for the child that could assist the child witness and encourage
      accurate testimony, as well as continue to protect the rights of the accused.

PMID- 7804773
TI  - Sideband analysis in DOR NMR spectra. I. "Infinite" inner-rotor speed.
AB  - DOR (double orientation rotation) solid-state NMR spectra are analyzed. All
      mathematical tools useful for describing the DOR spectra of nuclei simultaneously
      subjected to CSA and quadrupole interactions with non-coincident PAS are
      developed. The "infinite" inner-rotor speed approximation is described. The
      corresponding spectra observed in synchronized or unsynchronized experiments are
      analyzed. The rf pulse and recycle time effects are observed and explained. The
      comparison of MAS and DOR spectra on several compounds allows the determination
      of when the DOR technique is preferred to the MAS technique.

PMID- 7804774
TI  - Sideband analysis in DOR NMR spectra. II. Real finite inner-rotor speed.
AB  - DOR (double orientation rotation) solid-state NMR technique is analyzed
      specifically in the case where numerous (> 4) sidebands are observed on the
      spectrum. In this case, a rough spectrum analysis leads to the false observation
      of several impurity species. The total "visible" intensity is smaller than the
      real one. This may lead to an apparent relative concentration change when several
      species with very different quadrupole interactions coexist in the sample.
      Contrary to the MAS technique, the correct analysis of DOR spectra with sidebands
      very often necessitates the simultaneous introduction of CSA and quadrupole
      interactions.

PMID- 7804775
TI  - Improvements to the magic angle hopping experiment.
AB  - Several improvements to the magic angle hopping experiment first introduced by
      Bax et al. [J. Magn. Reson., 52 (1983) 147] are presented. A dc servo motor
      driven sample hopping mechanism which requires less than 60 ms to accomplish a
      120 degrees sample rotation is described. Modifications to the data acquisition
      process, including starting the acquisition period immediately after the second
      hop and acquiring a hypercomplex data set, are also presented. Principal values
      of the 13C chemical shielding tensor are measured for 1,2,3-trimethoxybenzene and
      2,6-dimethoxynaphthalene.

PMID- 7804776
TI  - Solid-state 31P CP/MAS NMR vs. solution study of bis(tertiary phosphines).
AB  - Solid-state 31C CP/MAS results of several diphosphines are compared with solution
      phase data. Non-equivalence of the P atoms are observed in the solid state for
      the less flexible derivatives (including all chiral diphosphines studied),
      whereas the more flexible compounds with a linear alkyl chain such as the 1,2
      ethane and the 1,4-butane derivatives give only rise to a single resonance. For
      the more strained bis(diphenylphosphino)methane contradictory data have been
      reported. Our experiments confirm the existence of an AB spin system, i.e., two
      different P atoms in solid state. Substantial chemical shift difference between P
      atoms have been observed in the solid state but not in solution of the chiral
      compounds. A possible explanation is suggested in terms of the concerted
      anisotropic effect of the phenyl rings attached to the phosphorus atom.

PMID- 7804777
TI  - Solid-state NMR study of ordered mesoporous aluminosilicate MCM-41 synthesized on
      a liquid-crystal template.
AB  - A novel mesoporous aluminosilicate MCM-41, synthesized in a liquid-crystal
      system, was characterized by magic angle spinning NMR. Conventional Bloch decay
      and cross-polarization spectra were compared. The 27Al spectra showed that the
      calcined material was highly siliceous, while 29Si NMR proved that it was rich in
      single and geminal silanol groups. Two kinds of the silanol groups were detected:
      exchanging and non-exchanging protons with water on the timescale of the 1H
      experiment. The 13C spectra of the uncalcined material were consistent with the
      concept of the micellar arrangement of the cetyltrimethylammonium template inside
      MCM-41.

PMID- 7804778
TI  - Proton NMR study of molecular motion in solid cortisone.
AB  - Polycrystalline cortisone (17,21-dihydroxy-4-pregnene-3,11,20-trione, C21H28O5)
      has been investigated by proton NMR methods between 56 and 400 K at 14 and 25
      MHz. Reductions in second moment and two very well-resolved minima in the spin
      lattice relaxation time at both frequencies are attributed to reorientation of
      the two methyl groups on carbons 18 and 19. The data are very well fitted over
      the entire temperature range to the Kubo-Tomita dipolar relaxation theory using
      the same parameters at both frequencies. Activation energies Ea characterizing
      the hindrances to the two methyl reorientations were 5.9 and 15.5 kJ/mol, an
      unusually large difference. The relaxation constants were 6.4 and 7.9 x 10(8) s
      2.

PMID- 7804779
TI  - Ab initio calculations of the 1H and 14N NMR shielding constants in solid
      ammonia.
AB  - The gauge-independent atomic orbital (GIAO) approach is used within the coupled
      Hartree-Fock (CHF) approximation to compute the 1H and 14N NMR shielding
      constants in solid ammonia. A comparison with gaseous NH3 shows that (a) both
      shielding constants are decreased to values belonging to the liquid state and (b)
      anisotropies of the two shielding constants are changing in opposite directions,
      i.e. a decrease for the nitrogen nucleus and an increase, smaller than the
      decrease, for the protons are observed.

PMID- 7804780
TI  - Transverse relaxation times of spin 3/2 nuclei in the quadrupole nutation NMR
      experiment.
AB  - Transverse relaxation times in the rotating frame of quadrupolar nuclei with half
      integer spins are inversely proportional to the linewidth of quadrupole nutation
      NMR spectra. We apply fictitious spin -1/2 operators to I = 3/2 nuclei to derive
      correlations between the transitions of a multi-level system which affect nuclear
      relaxation. When omega rf << omega Q, all possible multiple-quantum transitions
      contribute to the transverse quadrupolar relaxation time in the rotating frame
      T2Qp. When omega rf >> omega Q, two of the three single-quantum transitions do
      not contribute. In the low-temperature region (outside the extreme narrowing
      limit), the contribution of double- and triple-quantum coherences to T2Qp goes
      through a minimum for omega rf << omega Q, while the triple-quantum coherence
      appears at zero frequency and corresponds to a short transverse relaxation time
      for omega rf >> omega Q.

PMID- 7804782
TI  - Conventions for the reporting of nuclear magnetic shielding (or shift) tensors
      suggested by participants in the NATO ARW on NMR shielding constants at the
      University of Maryland, College Park, July 1992.

PMID- 7804781
TI  - 11B MAS NMR spectroscopy for characterizing the structure of glasses.
AB  - 11B MAS NMR spectroscopy has been shown to deliver reliable parameters for the
      chemical shift and the quadrupole interaction in glasses if short excitation
      pulses, high-speed magic angle spinning and satellite transition spectroscopy are
      applied. It is possible, in particular, to separate the contributions for
      trigonal BO3 and tetrahedral BO4 units to determine the relative fractions of
      both, and to use the isotropic chemical shift values as a sensitive probe for the
      nearest and next nearest environments of the boron atoms. The potential of the
      method has been demonstrated for some borate and borosilicate glasses prepared by
      the alkoxide gel techniques.

PMID- 7804783
TI  - Quantitative structural analysis of mullite by 27Al nuclear magnetic resonance
      satellite transition spectroscopy.
AB  - 27Al Nuclear magnetic resonance (NMR) satellite transition spectroscopy has been
      used for the quantitative investigation of the microstructure of polycrystalline
      2/1-type mullite (approximately 76 wt.-% Al2O3 and 24 wt.-% SiO2). Using this
      method the chemical shifts, quadrupole interaction parameters and relative amount
      of Al in the various coordination polyhedra have been obtained with high
      accuracy. The additional suppression of second-order quadrupolar broadening of
      the 27Al magic-angle spinning (MAS) spinning sidebands of the inner satellite
      transitions allows three different AlO4 units to be detected. The three AlO4
      resonances with isotropic chemical shifts at 68, 53 and 45 ppm are associated
      with AlO4 polyhedra in the tetrahedral double chains [AlO4(T)], the tetrahedra
      adjacent to the oxygen vacancies [AlO4(T*)] and the tetrahedra AlO4(T') linked by
      Oc* with AlO4(T*), respectively. Our NMR study of a polycrystalline sample
      supports the results of previous single-crystal studies of Angel et al. [Am.
      Mineral., 76 (1991) 332], especially the exclusion of silicon from the
      tetrahedral sites linked by Oc*.

PMID- 7804784
TI  - Multiple-quantum nuclear magnetic resonance spectroscopy of coupled 1/2 spins in
      solids. Combination with cross-polarization and magic-angle spinning.
AB  - Proton multiple-quantum coherence spectroscopy has been combined with magic-angle
      spinning (MAS) and cross-polarization (CP). This enables the detection of the
      proton (or any other abundant spin) multiple-quantum coherence spectrum via the
      high-resolution 13C (any other spin) nuclear magnetic resonance (NMR) spectrum.
      For this purpose multiple-quantum pulse sequences synchronised to sample rotation
      have been designed, and the average Hamiltonians of these sequences have been
      analysed. The analysis allows the design of optimal experimental conditions. As a
      demonstration of the technique, it has been applied to a mixture of adamantane
      and hexamethylethane. From earlier 13C spin diffusion experiments it was known
      that these two molecules form a mixed crystal. With our technique we detected two
      different phases with different molecular translational self-diffusion
      coefficients in this system.

PMID- 7804785
TI  - Solid-state nuclear magnetic resonance studies of acid sites in zeolites.
AB  - 2H Magic-angle spinning nuclear magnetic resonance (MAS NMR), echo 27Al NMR, two
      dimensional (2D) echo 1H MAS NMR and 1H, 27Al and 29Si MAS NMR have been applied
      to study the acid sites of dehydrated zeolites. The quadrupole coupling constants
      CQCC determined from 2H MAS NMR spectra of Si-OH-Al sites increase with the
      framework aluminium content of the zeolites from 208 Hz (H-ZSM-5) to 236 kHz (H-X
      and H-Y) due to the decreased acid strength of the bridging OH groups. The 27Al
      signal of the Si-OH-Al sites, which was considered "NMR-invisible" in the past,
      yields CQCC = 16 MHz for zeolite H-ZSM-5. The majority of non-framework aluminium
      species could also be observed in dealuminated and dehydrated zeolites H-ZSM-5
      giving CQCC approximately 9 mHz. 2D echo 1H MAS NMR spectra yield values of 16-40
      ms for the lower limits of the lifetime of hydroxyl species at room temperature.
      A lifetime of more than 40 ms was obtained from echo 2H MAS NMR spectra for
      protonated sites giving a signal at ca. 6.5 ppm in partially dealuminated and
      weakly rehydrated samples.

PMID- 7804786
TI  - Density operator formalism for the description of coherence evolution of a
      homonuclear two-spin system in rotating solids.
AB  - Based on a simple disentangling technique of the propagator, a density operator
      formalism is developed to describe the behavior of a homonuclear two-spin system
      in rotating solids. It is shown that the coherence evolutions can be
      characterized in terms of quaternions or a rotation matrix in a three-dimensional
      space; the coherence transfers between two different spins can thus be analysed
      well.

PMID- 7804787
TI  - Molecular motions and phase transitions in solid bis-n-propylammonium
      pentabromoantimonate.
AB  - The proton nuclear magnetic resonance (NMR) second moment and spin-lattice
      relaxation time for polycrystalline bis-n-propylammonium pentabromoantimonate
      (nPBA) have been measured from 70 to 290 K. The results are interpreted in terms
      of the CH3 and NH3 group reorientations for which the activation parameters have
      been determined. A structural phase transition evidenced at about 220 K is found
      in the polycrystalline sample of nPBA.

PMID- 7804789
TI  - Organ interactions in critical illness: paradigms and mechanisms.

PMID- 7804788
TI  - Proton dynamics in solid dopamine and noradrenaline hydrochloride.
AB  - Proton spin-lattice relaxation times (T1) have been measured as a function of
      temperature for the following catecholamines: dopamine hydrochloride and
      adrenaline hydrochloride. For both substances a single symmetric minimum of T1 is
      observed which can be explained as a result of NH3 (dopamine) and CH3
      (adrenaline) reorientation around the three-fold axis of the C-N bond. The
      activation parameters have been determined.

PMID- 7804790
TI  - Central nervous system regulation of cardiovascular homeostasis.
AB  - Moment-to-moment regulation of sympathetic and parasympathetic neural activities
      to the heart and peripheral circulation are vital to effective cardiovascular
      homeostasis. The arterial baroreflex serves as a major regulator in these
      activities. Consequently, central regulation of the operational point of the
      reflex may serve as a major determinant of neural outflow and hemodynamic
      stability in the critically ill.

PMID- 7804791
TI  - Central nervous system modulation of respiratory function in the critically ill.
AB  - Neural control of ventilation is exercised at multiple levels and includes an
      array of sensors and diverse control areas. Abnormalities in the neural control
      of ventilation are seen in a variety of pathologic states and illnesses commonly
      seen in critical care. As is common with any complex system, multiple feedback
      loops work within the system. Interactions between drive and performance are
      common in mechanically ventilated patients, especially during weaning from the
      ventilator. Better understanding of these interactions will hopefully lead to
      better understanding of the common pathologic processes involving control of
      breathing.

PMID- 7804792
TI  - The stress response in critical illness.
AB  - Under normal, unstressed conditions, the body maintains a dynamic equilibrium
      known as homeostasis--a complex interplay balancing the conflicting demands
      presented by many internal and external forces. In the face of threatened or
      actual disruptions (i.e., stress), molecular, cellular, physiologic, and
      behavioral responses act to restore homeostasis. These responses can be specific
      to a particular stressor and relatively circumscribed (e.g., secretion of insulin
      in response to an increase in blood glucose), or can be generalized and
      relatively nonspecific (e.g., behavioral manifestations of severe anxiety).
      Typically, more nonspecific and generalized responses occur in the setting of
      severe and threatening disruptions in homeostasis, and taken together, these
      responses are known as the "general adaptation or stress syndrome". We will
      describe the elements and organization of the generalized stress response with
      particular attention to the hypothalamic-pituitary-adrenal axis as it interacts
      with the immune system, and we will review what is known about this interactive
      network in the setting of critical illness.

PMID- 7804793
TI  - Endocrine response to brain injury.
AB  - The neuroendocrine response (NER) is an essential component of the adaptive
      process to trauma, brain injury, and major surgery. While receiving additive
      humoral and neural afferent inputs, the brain nuclei responsible for the NER act
      mainly by efferent pathways to the hypothalamic-pituitary-adrenal (HPA) axis and
      the sympathoadrenal system, the activations of which induce subsequent
      circulatory and metabolic responses. The NER to brain injury is similar to the
      response observed in patients with extracerebral injury, even if the response
      after brain injury is extremely variable. Generally, there is a biphasic pattern,
      with a sympathoadrenal storm associated with variable and altered stimulation of
      the HPA during the ebb phase. The first phase is followed by a decrease in both
      responses while other endocrine changes develop, involving mainly the counter
      regulatory, gonadal, and thyroid hormones. The outcome after brain injury is
      closely correlated with the intensity of these changes, particularly with
      catecholamine plasma levels and the severity of the low triiodothyronine
      syndrome. Alterations of the thyroid hormones are largely related to a reduction
      in peripheral deiodination of thyroxin. Recent research shows that increased free
      radical production and decreased selenium (an antioxidant) serum levels play an
      important role in thyroid metabolism. Two major issues remain unsolved: a) the
      precise definition of cerebral death, since endocrine brain function is not
      abolished in the state currently defined as brain death; and b) the question of
      whether substitutive hormone therapy should be applied in severe brain injury.

PMID- 7804794
TI  - Heart-lung interactions during positive-pressure ventilation.
AB  - Artificial ventilation using intermittent positive airway pressure is the
      mainstay support of patients in respiratory failure. By maintaining alveolar
      ventilation and alveolar stability, positive airway pressure can sustain
      respiratory gas exchange between the lungs and circulation, thereby supporting
      pulmonary homeostasis in patients who would otherwise be unable to maintain
      oxygen transfer and CO2 elimination. However, positive-pressure ventilation (PPV)
      also results in complex cardiovascular interactions. More often than not, these
      interactions impede blood flow through ventilated lungs and reduce global cardiac
      output. Although arterial oxygen content is adequately sustained because oxygen
      delivery is equal to the product of arterial oxygen content and cardiac output,
      global oxygen delivery may be reduced by PPV because of a decrease in cardiac
      output. Because a primary function of the cardiovascular-respiratory system is to
      deliver sufficient amounts of oxygen to meet systemic metabolic demands,
      measurement of arterial blood gases alone in monitoring ventilatory support is
      inadequate in assessing the cardiopulmonary effects of PPV. Clear understanding
      of cardiopulmonary interactions associated with mechanical ventilation is
      required in the rational management of critically ill ventilator-dependent
      patients. The hemodynamic effects of mechanical ventilation are complex and
      cannot be explained in terms of the interactions of single hemodynamic processes
      and cardiac function. However, when considered in this manner, such interactions
      can be understood more easily. In most patients it is usually clear which process
      is dominant, permitting adjustments in overall therapy in order to optimize care.
      This review identifies these interactions and demonstrates which are dominant in
      specific clinical scenarios.

PMID- 7804795
TI  - Cardiopulmonary interactions in acute lung injury: clinical and prognostic
      importance of pulmonary hypertension.
AB  - Development of acute lung injury (ALI) in the critically ill is associated with
      an array of abnormal interactions between the heart and lungs. Of these
      abnormalities, increased pulmonary vascular resistance (PVR) is common and seems
      to indicate a worse prognosis than when PVR is normal. Increased pulmonary artery
      pressure, which follows ALI in humans, has been attributed to many factors. Early
      in ALI, pulmonary artery hypertension (PAH) is secondary to an imbalance between
      the release of vasoactive mediators derived from arachidonic acid, endothelium
      derived relaxing factor, and other metabolites. As ALI progresses, the
      combination of mechanical obstruction and severe regional hypoxic pulmonary
      artery vasoconstriction probably becomes the main factor responsible for PAH. In
      addition to these elements, in situ and peripherally derived thromboemboli can be
      seen in ALI, owing to diverse disturbances in the coagulation and fibrinolytic
      processes. The result is increased workload of the right ventricle which is
      caused by increased afterload and may induce hemodynamic disturbances that
      culminate in overt right ventricular failure. However, epidemiologic studies have
      demonstrated that death following ALI is more often the result of respiratory
      failure or sepsis. The absence of effective therapy for PAH in ALI might be
      explained by the pathophysiological and clinical course of the disease. A
      reasonable conclusion from the contributing elements cited above is that PAH
      complicating sepsis and trauma is simply a marker of the gravity of the systemic
      insult that leads to the development of ALI and probably not a separate process.

PMID- 7804796
TI  - Pulmonary microvascular injury following intestinal reperfusion.
AB  - Multiple organ failure is the most common cause of death in critically ill
      patients in the United States. Acute respiratory failure is the most important
      single component of this clinical scenario, with a mortality risk > 50%. Key
      pathophysiologic events occur in the pulmonary microvasculature at the interface
      between circulating elements and the external environment. In particular, the
      response of the alveolar capillary endothelial cell is of fundamental importance
      in this injury process. A variety of clinical stimuli initiate a systemic
      inflammatory response that contributes to acute microvascular lung injury.
      Sepsis, trauma, thermal injury, acute pancreatitis, and ischemia-reperfusion
      injury are among these stimuli. The particular emphasis of this review is on
      events associated with intestinal ischemia-reperfusion, a common and important
      clinical event. The pathogenic mechanisms that lead to acute lung injury in this
      setting are not completely understood, although it is clear that neutrophil
      endothelial interactions regulated by both humoral and local mediators are
      crucial. Oxygen-derived free radicals, proteases, cytokines, eicosanoids,
      endotoxin, complement activation products, and probably platelet activating
      factor and nitric oxide are involved as either signalling or effector molecules.
      The key cellular participants during the acute phase of injury are the
      polymorphonuclear neutrophil (PMN) and the microvascular endothelial cell. Each
      of these participants is considered with regard to phlogistic behavior and the
      potential for therapeutic intervention. Adherence of the neutrophil to the
      endothelium creates a microenvironment in which PMN-derived oxidants, proteases,
      and cationic proteins are discharged under conditions that lead to cellular
      injury. Loss of microvascular integrity results and pulmonary dysfunction
      follows. At present, we offer only nonspecific supportive care for patients with
      this problem. However, investigations into relevant molecular and cellular
      regulatory events offer important opportunities for directed therapy. We are now
      approaching the threshold for utilization of several new and specific approaches.
      While no single pharmacologic therapy is likely to be curative for this complex
      problem, it is probable that certain approaches will be of clinical benefit in
      the near future. This review is designed to provide a basis for understanding
      this evolution.

PMID- 7804797
TI  - Gastrointestinal tract dysfunction in critical illness: pathophysiology and
      interaction with acute lung injury in adult respiratory distress
      syndrome/multiple organ dysfunction syndrome.
AB  - The adult respiratory distress syndrome (ARDS), a common complication of critical
      illness, is associated with a > 50% mortality rate. Refractory respiratory
      failure is, however, an uncommon cause of mortality in these patients. Most
      deaths are due to a syndrome of relentless organ dysfunction accompanied by
      abnormal organ system interactions, collectively referred to as the multiple
      organ dysfunction syndrome (MODS). MODS is associated with two chief
      pathophysiologic derangements: a) the unregulated activation of systemic
      inflammatory cascades; and b) alterations of oxygen uptake (VO2)-oxygen delivery
      (DO2) relationships. Current concepts regarding the pathophysiology of MODS,
      specifically its relationship to unregulated systemic inflammation and
      alterations in VO2-DO2 alterations, are discussed. Within this framework, current
      and future areas for investigation that may result in mechanism-specific
      innovations with the potential to interrupt events mediated by gastrointestinal
      dysfunction that lead to MODS are presented.

PMID- 7804798
TI  - Liver-lung interactions in critical illness.
AB  - Organ interactions are increasingly recognized as key determinants of the
      pathogenesis and potential for resolution of tissue injury during critical
      illness. A paradigm for a systems model that takes into account the modulatory
      effects of organ interactions and incorporates the expanding number of molecular
      and cellular pro-inflammatory networks is still lacking. Unifying hypotheses for
      multiple organ dysfunction during the systemic inflammatory response syndrome
      have been slow to emerge. The liver plays a central role in the regulation of
      multiple host defense, immunologic, biochemical, and metabolic functions during
      sepsis and trauma. However, the liver is relatively inaccessible for clinical
      study and its function is often non-specifically defined. Consequently, the
      liver's pathogenetic importance within a regulatory network of mediator and organ
      interactions during inflammatory responses leading to acute lung injury is poorly
      appreciated. This review addresses the concept that hepatic performance, broadly
      defined, represents a point of convergence in which four regulatory elements of
      the acute inflammatory response interact over a host defense continuum to affect
      lung function. These regulatory elements include: a) control of systemic
      endotoxemia, bacteremia, and vasoactive by-products of sepsis and trauma by the
      gut-liver axis of inflammation, mononuclear phagocytic clearance, and Fc and
      complement receptor-mediated events; b) production and export of endogenous
      cytokine and eicosanoid mediators by Kupffer cells, especially in relation to
      changes in the prevailing hepatic oxygen supply; c) metabolic inactivation and
      detoxification of such mediators via cell-to-cell interactions at the Kupffer
      cell-hepatocyte interface; and d) cytokine-driven synthesis of acute-phase
      proteins that critically modulate metabolism and inflammation. Our goal is to
      summarize and integrate recent information that sheds light on mechanisms by
      which hepatic function modulates host defense homeostasis, thereby influencing
      pulmonary function in the adult respiratory distress syndrome. Liver-lung
      interactions are presented as a heuristic paradigm of organ interactions that
      dynamically modulate systemic immunophysiologic responses during critical
      illness.

PMID- 7804799
TI  - Pathogenetic mechanisms of acute hepatic encephalopathy.
AB  - With the advent of liver transplantation as an accepted therapy for end-stage
      liver disease, increasing numbers of patients with severe hepatic dysfunction
      require ICU stabilization and treatment of associated complications. Of these,
      acute hepatic encephalopathy remains an important cause of morbidity and
      mortality. We review recent findings concerning interactions between the damaged
      liver and the brain that may have direct clinical implications in the management
      of hepatic encephalopathy in the critically ill.

PMID- 7804801
TI  - Metabolic encephalopathy as a complication of renal failure: mechanisms and
      mediators.
AB  - Among patients with end-stage renal disease, nervous system dysfunction remains a
      major cause of disability. Patients with chronic renal failure who have not yet
      received dialysis may develop symptoms ranging from mild sensorial clouding to
      delirium and coma. Dialysis itself is associated with at least three distinct
      disorders of the CNS: dialysis disequilibrium syndrome; dialysis dementia; and
      progressive intellectual dysfunction. Peripheral neuropathy is also a major cause
      of disability in uremic subjects. It is believed that aluminum contributes to the
      pathogenesis of dialysis dementia. Biochemically, brain calcium is elevated in
      patients with renal failure, probably because of actions of parathyroid hormone
      on the brain. The diagnosis of dialysis disequilibrium syndrome, intellectual
      dysfunction, dialysis dementia, and uremic neuropathy can be made by the
      characteristic clinical pictures of these syndromes and the exclusion of other
      causes of nervous system dysfunction.

PMID- 7804800
TI  - Pulmonary-renal axis during positive-pressure ventilation.
AB  - Controlled mechanical ventilation with positive end-expiratory pressure (PEEP) is
      generally associated with decreases in urine volume and renal sodium excretion.
      The resulting positive sodium and water balance is an undesirable side effect of
      controlled mechanical ventilation with PEEP. The increase in intrathoracic
      pressure initiates a cascade of hemodynamic, neural, and hormonal changes which,
      in turn, stimulate the kidney to decrease the glomerular filtration rate and
      increase tubular reabsorption. The redundancy of these regulatory mechanisms
      makes it difficult to determine the involvement of only one or two single
      parameters as causative events of the phenomenon.

PMID- 7804802
TI  - Organ interactions in the hepatorenal syndrome.
AB  - An increasing number of patients with severe liver dysfunction are admitted to
      the ICU for stabilization and organ-specific support, including liver
      transplantation. Global impairment of hepatic performance frequently results in
      pathologic organ interactions that limit the potential for recovery. One of the
      most notable of these interactions is the hepatorenal syndrome, an otherwise
      uniformly fatal complication of end-stage liver disease characterized by the
      progressive development of oliguria and low urine sodium excretion. The syndrome
      can occur in the setting of either acute or chronic liver disease, and portal
      hypertension may be important in the pathogenesis. The patient with the
      hepatorenal syndrome also has a number of systemic circulatory abnormalities
      induced by liver disease and/or portal hypertension, but the exact pathologic
      role of these abnormalities in the development of oliguria is uncertain. It is
      reasonably well established that diminished systemic BP characteristic of liver
      failure is not the primary cause of renal insufficiency. Rather, intrarenal
      preglomerular vasoconstriction mediated by unknown stimuli is the major defect in
      the hepatorenal syndrome, manifested by relative ischemia. Current data point to
      abnormal renal sympathetic innervation as one of the more likely major causes of
      this vasoconstriction. After exclusion of systemic intravascular volume depletion
      and other causes of oliguria, dialytic therapy is indicated when liver
      transplantation or recovery of liver function is anticipated; terminal supportive
      care is appropriate when these outcomes are not options.

PMID- 7804803
TI  - Leukocyte-endothelial interactions and organ injury: the role of adhesion
      molecules.
AB  - Polymorphonuclear neutrophils (PMN) play an important role in host defense and
      immune surveillance. However, PMNs can be detrimental when inflammatory stimuli
      are excessive and can lead to uncontrolled PMN adherence to microvascular
      endothelium, resulting in tissue and organ injury in the critically ill. The
      molecular basis of PMN-endothelial adherence is dependent on two groups of
      adhesion molecules and their co-specific ligands: the beta 2 integrins and their
      counterstructures, which are members of the immunoglobulin gene superfamily; and
      the selectins and their carbohydrate ligands expressed on vascular mucins and
      other glycoproteins or glycolipids. This review characterizes the events leading
      to PMN-endothelial adhesion and examines a number of in vivo models in which
      adhesion molecule blockade has protected against injury. The role of adhesion
      molecules in T-lymphocyte adhesion and immune surveillance of transplant
      allografts is also briefly discussed. The infectious risks of adhesion molecule
      blockade are reviewed.

PMID- 7804804
TI  - The inflammatory-coagulant axis in the host response to gram-negative sepsis:
      regulatory roles of proteins and inhibitors of tissue factor.
AB  - Reciprocal interactions between elements of the acute inflammatory response and
      the coagulation system play important roles in host defense homeostasis during
      Gram-negative bacterial sepsis. However, derangements in the regulation of the
      inflammatory-coagulant axis in this setting may result in progressive tissue
      damage and disseminated intravascular coagulation. In this article, the
      integrated responses in the baboon model of Escherichia coli sepsis are analyzed
      as a basis of understanding these response interactions in the critically ill. In
      particular, three topics will be reviewed. First, the role of tissue factor in
      mediating the coagulant response to inflammation and the role of tumor necrosis
      factor (TNF) in initiating and amplifying this coagulant response into a full
      blown consumptive coagulopathy are defined. A second and parallel topic concerns
      the role played by tissue factor pathway inhibitor and other anticoagulant
      systems in not only regulating this coagulant response, but also in attenuating
      the initial inflammatory response. The third topic concerns the use of assays of
      enzyme inhibitor complexes composed of components of these regulatory
      anticoagulant systems to help define the hypercoagulable state and possibly to
      make an early, specific diagnosis of sepsis prior to overt failure of the
      hemostatic system.

PMID- 7804805
TI  - Extravascular coagulation and fibrin deposition in acute lung injury.
AB  - Extravascular fibrin deposition is characteristic of the acute inflammatory
      response and is, for example, prominent in the alveolar compartment of patients
      with the adult respiratory distress syndrome. Fibrin deposition in the injured
      lung is regulated by a balance of locally expressed pathways of coagulation and
      fibrin clearance, called fibrinolysis. These pathways comprise part of the
      interactive network of responses that influence local inflammatory cell traffic,
      microvascular permeability, and repair mechanisms. In this sense, fibrin turnover
      in the lung extends beyond traditional hemostasis and may influence the acute
      inflammatory response and resolution. Within the injured alveolar compartment,
      fibrin deposition is initiated by increased activity of the extrinsic coagulation
      pathway-tissue factor associated with factor VII. Activation of the contact and
      intrinsic coagulation pathways also occurs. Local fibrinolysis is generally
      impaired, which may potentiate extravascular fibrin deposition. Fibrin turnover
      in the adult mammalian lung is similarly disrupted in several forms of injury but
      differs from the injury that occurs in the lungs of premature infants with
      respiratory distress.

PMID- 7804806
TI  - The pathophysiology and organ-specific consequences of severe transfusion
      reactions.
AB  - Transfusion of blood components is usually required in the management of
      critically ill patients. However, pathologic interactions between blood products
      and organ function may result from transfusion reactions. Emerging understanding
      of the mediation and interruption of clinical inflammatory responses is
      applicable to severe transfusion reactions. The pathophysiology of four types of
      severe transfusion reactions are reviewed: a) acute hemolysis; b) bacterial
      contamination of blood components; c) transfusion-related acute lung injury
      (TRALI); and d) anaphylaxis. Acute hemolytic reactions are often caused by
      preventable errors in sample or patient identification. Renal toxicity,
      coagulopathy, and hypotension may result from circulating red cell stroma and
      immune-complex activation of complement and cytokine secretion. Bacterial
      contamination of blood components has caused patient sepsis in many cases;
      platelets stored at 20 degrees to 24 degrees C are of particular concern. Careful
      blood collection and handling is essential for prevention. TRALI is manifested by
      acute respiratory distress, which is usually caused by infusion of plasma
      containing antibodies against the patient's leukocytes. Complement activation and
      cytokine stimulation cause edema and neutrophil accumulation in the lungs.
      Anaphylactic reactions may result from patient immunoglobulin (Ig)E antibodies
      against donor plasma constituents. IgA-deficient patients are at risk for
      anaphylactic reactions if these patients develop anti-IgA antibodies. Vasoactive
      or complement-activating factors in a blood product may also cause anaphylactoid
      reactions in some patients.

PMID- 7804807
TI  - [Pathogenesis of asthma].

PMID- 7804808
TI  - [Descriptive study of morbidity and mortality due to asthma at a Health Sector
      institution].
AB  - The objective of this study was to determine the morbidity and mortality rate due
      to asthma from a Health Institution, which represents the majority of working
      population. Asthma data were obtained from the National Institute of
      Informatical, Geography and Statistics (INEGI), Mexican Health Secretary (SS) and
      Mexican Social Security Institute (IMSS). The underlying cause of death
      hospitalization or visit were obtained. Asthma was coded according to the
      International Classification of Disease (ninth revision). Asthma death rate was
      adjusted by age using direct method. In the IMSS, asthma death rate increased
      from 3.24/200,000 in 1980 to 12.76/100,000 in 1990. The asthma letality increased
      from 0.34 in 1980 to 1.23 in 1990. The average length of hospital stay was 3.96
      days in 1990; there was noy significant differences by sex the most affected
      groups were children under 4 years of age and persons older than 65 years of age.
      In conclusion, from 1980 to 1990, the morbidity and mortality rate due to asthma
      in IMSS increased. It suggests that future health policy efforts should be
      focused to reduce the morbidity, mainly in high risk groups.

PMID- 7804809
TI  - [Identification of antinuclear, nucleolar and SS-A antibodies, using an
      immunoassay system].
AB  - In this paper we report a solid phase ELISA for screening of antinuclear,
      nucleolar, and SS-A antibodies. The test system was evaluated with 158 sera that
      were positive by immunofluorescence (IF), some of which were immunologically
      characterized as containing antibodies to Sm, RNP, SS-A, SS-B, nucleolar, and
      DNA, and 247 IF negative that were used as a control group. Ninety eight per cent
      of serum samples with an antibody of known specificity and/or positive IF, were
      positive by the ELISA system including antinucleolar samples. Reproducibility of
      the assay was demonstrated by using five sequentially prepared antigenic
      extracts. The lineal regression from the last experiment was between 0.75 and
      0.91. With this system, positive and negative ANA can be identified as the
      screening procedure without the need of additional studies. To our knowledge this
      is the first ELISA system report for the screening of antinucleolar antibodies.

PMID- 7804810
TI  - [Asthma induced by aspirin and arachidonic acid metabolites. Role of leukotrienes
      (third part)].
AB  - Although the mechanism of aspirin-induced asthma is unknown, it has been
      suggested that adverse nasal and bronchial reactions are caused by an increased
      production of lipoxigenase products. In examining the hypothesis of inhibition on
      cycloxigenase, we support evidence in favor of this theory. We have measure the
      release of urinary LTE4, TXB2 and 11-dehydro-TXB2 of aspirin-induced asthmatics
      and controls by radioimmunoassay and HPLC methods during aspirin challenge and
      after desensitization. The over production demonstration of urinary LTE4 during
      aspirin challenge and the decrease after desensitization in inversal direct
      proportion manner with TXB2 suggest a "shunting" of the arachidonic acid
      metabolites of the target cells. Whichever theory is to be pursed further, it
      must also accommodate the clinical effect of aspirin desensitization.

PMID- 7804811
TI  - [Multiple sclerosis].
AB  - Multiple sclerosis, a neurological problem in which mechanisms of autoimmunity
      and immunodeficiency may cause damage appears with a variable range of immune
      response. In this paper we classify in three grate subgroups the alterations
      observed in our patients: Type I: specific defect of immune response; Type II:
      immunodeficiency with autoimmune responses; Type III: mixed responses:
      autoimmunity with specific defect of immune response and increased cytotoxicity.
      A rational explanation about the various immunological changes emerged from
      comprehension of these mechanisms of response and following these hypothesis we
      propose an immunological classification of multiple sclerosis in other to reach
      more effective therapeutic goals.

PMID- 7804812
TI  - Academy of Aphasia annual meeting. Cambridge, Massachusetts, October 23-25, 1994.
      Abstracts.

PMID- 7804813
TI  - Isolator environments.

PMID- 7804814
TI  - U.S. v. Barr Laboratories: a technical perspective.

PMID- 7804815
TI  - Inspections: the international regulatory view.

PMID- 7804816
TI  - Inspections: the international regulatory view--Japan.

PMID- 7804817
TI  - Studies on the scale-up of microfiltration membrane devices.
AB  - This paper addresses the prediction and modeling of fouling in microfiltration
      (MF) membrane devices during the filtration of biological solutions. The membrane
      fouling model described can be used by bioengineers to characterize a solution's
      filterability when using a specific microfiltration product line. This allows
      bioengineers to predict the scale up of filtration from laboratory through
      clinical production to full marketing production. The model used to correlate
      filtration results contains two parameters (initial flux and membrane plugging
      constant) that must be determined experimentally. Once these parameters are
      known, it is possible to predict the performance (fouling and throughput) of
      larger membrane devices as a function of operating pressure, processing time, and
      membrane area. This allows users of MF devices to perform laboratory tests of
      their solution at relatively small scale, and based on these tests determine the
      performance of larger-scale MF devices for filtration of the same solution.

PMID- 7804818
TI  - Time-dependence of pressure in lyophilization vials.
AB  - Lyophilized pharmaceuticals are often sealed under reduced pressure and "vacuum
      testing" is done as a part of quality assurance. In this work the pressure Pv
      inside lyophilization vials was measured as a function of storage time after
      sealing at a chamber pressure Pc < 20 mtorr. Vials were of 50 mL nominal capacity
      (empty and with product) and 10 mL nominal capacity (with product). For all three
      sample types Pv was observed to rise to approximately 2 torr within ca. 50 hrs,
      then increase slowly to Pv = 5-10 torr after the lapse of 2300 hrs (3 months).
      Calculations based on outgassing and permeation of the stopper by O2, NH2 and H2O
      demonstrate that vial pressure is primarily due to desorption of water vapor from
      the stopper into the headspace of the vial. The presence of a hydrophilic product
      decreases the rate of pressure rise, and Pv increases more rapidly in smaller
      vials. Results are discussed in terms of testing for seal integrity and for
      stopper effects on moisture in the product.

PMID- 7804819
TI  - Validation of dry heat inactivation of bacterial endotoxins.
AB  - Bacterial endotoxins (ETs) are lipopolysaccharides from the cell wall of Gram
      negative bacteria. ETs get into the environment as a result of autolytic
      desintegration of the bacterial cells. There exist a number of depyrogenation
      methods, either serving to remove or to inactivate ET. The most common means of
      ET inactivation is dry heat. Unfortunately no uniform regulation exists
      describing the conditions for sufficient ET inactivation. While the USP and FDA
      require an ET reduction of 3 log steps, no European regulation exists regarding
      depyrogenation of final containers for parenterals. However, the Ph. Eur.
      specifies the temperature and time conditions for depyrogenation of glassware in
      the pyrogen test monograph, allowing to choose between the two variants 250
      degrees C/30 minutes or 200 degrees C/60 minutes which are not equivalent. In the
      present study those conditions for depyrogenation of glass containers in
      production of parenterals were investigated which, on the one hand, are
      technically feasible and, on the other hand, comply with the requirements of the
      main Pharmacopeias; furthermore, an ET preparation suitable for validation
      studies was selected. The preparation of ET indicators, the dry-heat inactivation
      and the recovery of ET are described in detail. Based on the results obtained, it
      is recommended to follow a defined treating temperature and period for safe
      depyrogenation of glass containers for parenterals, which results in a 4 log step
      reduction in ET without fillers. Thereby the USP/FDA requirement for a 3 log step
      reduction as well as the 200 degrees C/60 minutes requirement variant given in
      the Ph. Eur. can be fulfilled.

PMID- 7804820
TI  - Effect of sodium thiosulfate on the photolysis of phenobarbital: evidence of
      complex formation.
AB  - Photodegradation of phenobarbital in aqueous solutions exposed to short-wave
      ultraviolet light was studied in presence and in absence of sodium thiosulfate.
      The degradation process appeared to follow first-order kinetics and was found to
      be dependent on pH, buffer system and sodium thiosulfate concentration. Ionic
      strength did not have any appreciable effect. The rate of photodegradation was
      found to be inversely proportional to phenobarbital concentration, especially
      below 8 x 10(-4) M. Solutions of phenobarbital containing alcohol, propylene
      glycol and benzyl alcohol as cosolvents showed markedly improved stability under
      UV irradiation in absence of sodium thiosulfate. Complex formation between the
      thiosulfate anion and phenobarbital appeared to be primarily responsible for the
      photostabilization of the drug. The equilibrium constant for this complex was
      calculated to be 36.23 M-1.

PMID- 7804821
TI  - Sterile product pre-approval/post-approval inspections.

PMID- 7804822
TI  - Expression and distribution of two isoforms of tyrosine hydroxylase in macaque
      monkey brain.
AB  - In humans, the RNA for tyrosine hydroxylase (TH), the rate-limiting enzyme in the
      synthesis of catecholamines, can undergo alternative splicing to produce four
      different types of mRNA. Each of the predicted TH protein forms has been shown to
      be expressed in human brain, but constraints inherent in human postmortem studies
      require the use of an animal model to further explore the functional significance
      of multiple TH isoforms. Since the anatomical organization of catecholaminergic
      systems in Old World macaque monkeys appears to accurately predict their
      organization in humans, we used antibodies that selectively recognize each of the
      human TH isoforms to determine the expression and distribution of TH isoforms in
      monkey brain. Blot immunolabeling and immunocytochemical techniques demonstrated
      that catecholaminergic neurons of monkey brain express both type 1 and type 2 TH,
      but not type 3 or type 4. Thus, monkeys differ in the number of TH isoforms
      expressed in brain both from rodents (type 1 TH only) and humans (types 1-4 TH).
      In some catecholaminergic neurons and axon terminals of human brain, only type 1
      TH immunoreactivity was detectable, suggesting that the selective expression of a
      single isoform could occur or that TH isoforms might differ in their
      accessibility to or engagement with cell trafficking mechanisms. However, in
      monkeys there was no evidence for the selective expression or distribution of
      either type 1 or type 2 TH in any of the catecholaminergic cell bodies or
      terminal fields examined. In addition, quantitative blot immunolabeling studies
      demonstrated that type 1 and type 2 TH were present in the same relative
      abundances in monkey substantia nigra and caudate nucleus. Furthermore, studies
      in monkeys designed to model the human postmortem state revealed that the
      apparently selective distribution of TH isoforms seen in the human study could be
      created by postmortem effects. In summary, in contrast to nonprimate species,
      multiple protein isoforms of TH are expressed in monkey brain as well as in human
      brain. Although the precise functional role of each isoform has not been
      determined, their presence suggests that the regulation of catecholamine
      biosynthesis may be more complex and subject to alternative modes of regulation
      in primates than in nonprimate species. In addition, the difference between
      monkeys and humans in the number of TH isoforms may provide insight into a
      molecular basis for species differences in cognitive and other brain functions.
      However, both type 1 and type 2 TH, the two predominant isoforms of human TH, are
      expressed in monkey brain.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7804823
TI  - Elevation of neuronal MAO-B activity in a transgenic mouse model does not
      increase sensitivity to the neurotoxin 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP).
AB  - To examine whether expressing high levels of monoamine oxidase (MAO-B) activity
      abberently in neurons results in increased sensitivity of dopaminergic neurons to
      the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 8-week-old
      transgenic mice expressing high neuronal levels of MAO-B were compared with age
      matched nontransgenic littermates following i.p. injections of 30 mg/kg body
      weight of the protoxin. Levels of striatal dopamine (DA) and its metabolite 3,4
      dihydroxyphenylacetic acid (DOPAC), as well as tyrosine hydroxylase (TH)
      immunopositive cell numbers in the substantia nigra (SN) were compared 1 week
      later between transgenics and controls. No difference was found in any of these
      parameters, indicating that high neuronal MAO-B levels does not cause increased
      sensitivity to MPTP, and therefore neither conversion of MPTP to its active form,
      1-methyl-4-phenyl pyridium (MPP+) by MAO-B nor MPP+ uptake by the dopaminergic
      transporter are likely to be the rate-limiting step in the toxicity of this
      compound.

PMID- 7804824
TI  - Localization and characterization of epidermal growth-factor receptors in the
      developing rat medial septal area in culture.
AB  - The presence and binding properties of epidermal growth-factor receptors (EGF-Rs)
      in different cell types purified from the rat medial septal area in culture were
      investigated. We report that astrocytes, oligodendrocytes and neurons from this
      area possess EGF-Rs while microglia do not. EGF-binding sites are detectable on
      astrocytes derived from the medial septum of both embryonic and neonatal rats.
      Scatchard analysis of the data for astrocytes from the fetal rats show that EGF
      specifically binds to both high- (Kd = 7.21 x 10(-10) M, Bmax = 3602
      receptors/cell) and low-affinity (Kd = 3.99 x 10(-8) M, Bmax = 86,265
      receptors/cell) receptors on these cells. On the other hand, astrocytes purified
      from neonatal tissue possess a greater number of high-affinity receptors (Bmax =
      10,938 receptors/cell) when compared with the embryonic astroglia. With time in
      culture, the number of both types of receptors on neonatal astrocytes decreases.
      Oligodendrocytes also possess high- and low-affinity EGF-Rs with dissociation
      constants of 3.25 x 10(-10) M and 3.85 x 10(-8) M, respectively. The number of
      receptors on oligodendrocytes is significantly lower than those of neonatal
      astrocytes (Bmax = 1185 and 25,081 receptors/cell for high- and low-affinity
      binding sites, respectively). Finally, neurons from this area also exhibit two
      different EGF-R types with dissociation constants similar to those described for
      astrocytes. As the number of receptors/neuron (Bmax = 136 and 1159 receptors/cell
      for high- and low-affinity binding sites, respectively) appears to be extremely
      low, it is possible that EGF specifically binds only to a subpopulation of
      neurons from this area. These studies demonstrate which cell types in the
      developing medial septal area possess EGF-Rs and provide a detailed
      characterization of these binding sites. These EGF-R-bearing cells may be
      potential targets for this growth factor or for transforming growth factor alpha
      in this brain area.

PMID- 7804825
TI  - Rapid development of somatic spines in stratum granulosum of the adult
      hippocampus in vitro.
AB  - Somatic spines on granule cells have been observed occasionally in the adult rat
      dentate gyrus in vivo. Here we evaluate the appearance and formation of somatic
      spines in s. granulosum from adult rat hippocampal slices immediately after slice
      preparation, 45 min, 3 h, and 5 h later. Initially somatic spines are extremely
      rare but, after 3 h in vitro, they are readily apparent. Some of these somatic
      spines form asymmetric synapses that have a spherical vesicle-containing
      presynaptic bouton and a postsynaptic density. Other somatic spines lack a
      postsynaptic density and may also lack an apposed presynaptic bouton (free
      somatic spines) as observed in single thin sections. Both the number of these
      free somatic spines and the number of somatic spine synapses increase in a time
      dependent manner. No somatic spines were observed on CA1 pyramidal cells in the
      same hippocampal slices. Electrophysiological observations indicate that the
      formation of somatic spine synapses on granule cells in the hippocampal slice
      occurs without any apparent granule cell activation. The trigger event for this
      very rapid synaptogenesis in the adult dentate gyrus remains to be determined.

PMID- 7804826
TI  - Effect of food deprivation and streptozotocin-induced diabetes on hypothalamic
      neuropeptide Y release as measured by a radioimmunoassay-linked microdialysis
      procedure.
AB  - Central administration of neuropeptide Y (NPY) produces a robust feeding response
      in the rat. It is still unclear how, and in response to what endogenous stimuli
      NPY is released. We have developed a radioimmunoassay-linked microdialysis
      procedure for measuring hypothalamic NPY release in both the anaesthetised and
      freely moving rat. We have used the procedure to show that anaesthesia
      dramatically decreased NPY release, while a 48 h period of food deprivation
      significantly increased extracellular NPY concentrations. Streptozotocin-induced
      diabetic rats also showed increased hypothalamic NPY release compared to
      controls. These results provide more evidence that NPY may be involved in
      mediating the hyperphagia associated with starvation and diabetes mellitus. The
      development of a sensitive microdialysis procedure to measure NPY will allow
      further detailed investigation of the hypothalamic NPY system.

PMID- 7804827
TI  - Evidence for the association of protein 4.1 immunoreactive forms with
      neurofibrillary tangles in Alzheimer's disease brains.
AB  - The formation of neurofibrillary tangles (NFTs) and paired-helical filaments
      (PHFs) in Alzheimer's disease (AD) reflects a major disorganization of the
      cytoskeleton. The role of the neuronal membrane skeleton in the development of
      these abnormalities has not previously been investigated. In this study, we used
      9 antibodies raised against the erythrocyte membrane skeleton protein 4.1 (P4.1)
      for immunocytochemical and immunoblot analyses to investigate whether or not the
      brain homologues of this protein were constituents of NFTs or PHFs. Our results
      show that 7 of the 9 monospecific antibodies against the human and pig
      erythrocyte P4.1 stained NFTs in the prefrontal cortex and hippocampus of AD
      brains. The P4.1 antibodies used here did not cross-react with tau protein
      isolated from AD brain, and preabsorption of these antibodies with tau protein
      did not cause loss of NFT staining. In age-matched control brains, these P4.1
      antibodies stained neuronal cell bodies or nuclei. Six of the antibodies also
      stained isolated NFTs but the SDS-insoluble NFTs were immunostained only by two
      of the P4.1 antibodies. By using inositol hexaphosphate affinity chromatography
      and immunoblot analysis, we identified a 68-kDa protein as the most likely brain
      analogue of P4.1. When SDS-extracted proteins from the isolated NFTs were
      immunoblotted, a 50-kDa band was immunostained. The 68-kDa and 50-kDa proteins
      were not stained by tau protein and neurofilament subunit NF-H antibodies, that
      strongly stained NFTs. We conclude that brain protein 4.1 isoform(s) are
      constituents of NFTs in AD.

PMID- 7804828
TI  - Expression of cytokines during glial differentiation.
AB  - Astrocytes and microglia produce a variety of cytokines, some of which may have
      roles in the proliferation and differentiation of glial cells during development
      in the central nervous system. Cytokine mRNAs and activities were therefore
      assayed during glial development in mixed glial cell cultures from newborn mouse
      brain. Cytokine mRNAs were also measured in mouse brain during postnatal
      development in vivo. Macrophage colony-stimulating factor(M-CSF) mRNA,
      interleukin-1 beta (IL-1 beta) mRNA and tumor necrosis factor alpha (TNF alpha)
      mRNA were all detected on the in vitro cultures and each showed a distinct time
      course of expression. IL-6 and granulocyte-macrophage colony-stimulating
      factor(GM-CSF) mRNAs were not detected in the cultured cells. Measurements of
      cytokine activity in culture supernatants as well as cytokine mRNAs in vivo gave
      similar results. The data suggest that IL-1, TNF alpha and M-CSF are produced in
      the period of gliogenesis, and that M-CSF rather than GM-CSF may promote the
      generation and proliferation of microglia. Although IL-6 and GM-CSF exhibit
      neurotrophic effects, these cytokines may not function as neurotrophic factors
      during early postnatal development.

PMID- 7804829
TI  - The response of human and rat fetal ventral mesencephalon in culture to the brain
      derived neurotrophic factor treatment.
AB  - Brain-derived neurotrophic factor (BDNF) has been shown to increase the survival
      of dopaminergic neurons in rodent mesencephalic cultures. The mRNAs of BDNF and
      trkB receptor have been found to be expressed in the substantia nigra of rat. In
      this study, the action of BDNF was studied on the survival and transmitter
      specific differentiation of dopaminergic neurons of fetal human CNS aged 9-10
      week in vitro. Dopaminergic neuron viability and phenotypic expression were
      monitored by tyrosine hydroxylase (TH) immunohistochemistry and measurement of
      dopamine (DA) content with HPLC, respectively. After seven days of treatment with
      BDNF there were 2.2-fold greater number of TH+ neurons surviving than in
      untreated cultures. Although very low levels of DA were detectable in human
      tissue, considerable amounts of DA was found in the culture medium from around 13
      days in vitro (DIV), indicating that DA in human fetal tissue tended to be
      synthesised and released into the incubation medium more readily than from
      cultured rat fetal tissue during the same period. The content of DA in the BDNF
      treated cultures was approximately double that of untreated cultures after 7
      days. In rat fetal tissue, the capacity of each TH+ neuron to produce DA was not
      changed in the BDNF-treated cultures (7 DIV) compared with control cultures,
      suggesting that BDNF does not up-regulate the production of DA but rather acts to
      reduce cell death rates. Ciliary neurotrophic factor (CNTF) treatment of rat
      mesencephalic culture failed to improve the period of survival of fetal
      dopaminergic neurons and had no effect on the production of DA in
      cultures.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7804830
TI  - Attenuated hippocampal long-term potentiation in basolateral amygdala-lesioned
      rats.
AB  - Possible involvement of the amygdaloid input in long-term potentiation (LTP) in
      the medial perforant path-dentate gyrus granule cell synapses in vivo was
      investigated by evaluating the effects of lesions of the amygdaloid nucleus. The
      dentate gyrus synaptic potential evoked by low-frequency test stimulation did not
      change following lesions of the basolateral and central amygdala. However, when
      tetanic stimulation (30 pulses at 60 Hz) was applied 60 min after lesioning of
      the ipsilateral basolateral amygdala, the magnitude of LTP was significantly
      attenuated. Since lesions of the ipsilateral central amygdala and the
      contralateral basolateral amygdala did not affect the dentate gyrus LTP, the
      attenuation of the dentate gyrus LTP is a specific effect of acute lesions of the
      ipsilateral basolateral amygdala. The basolateral amygdaloid lesions
      significantly attenuated both LTP induced by weak (20 pulses at 60 Hz) and strong
      (100 pulses at 100 Hz) tetanus, indicating that the effect of the lesions does
      not depend on the strength of tetanus applied to induce LTP. When the ipsilateral
      basolateral amygdala was destroyed after application of tetanus, it did not
      affect the established LTP. The attenuation of LTP was also observed after the
      basolateral amygdala-lesioned rats were allowed a recovery period of 2 weeks.
      This is the first report providing evidence that the ipsilateral basolateral
      amygdala modulates hippocampal synaptic plasticity in vivo.

PMID- 7804831
TI  - Retention of basic fibroblast growth factor immunoreactivity in dopaminergic
      neurons of the substantia nigra during normal aging in humans contrasts with loss
      in Parkinson's disease.
AB  - A count of pigmented neurons per mm3 in sections of the substantia nigra at the
      level where the oculomotor nerve emerges in 11 neurologically normal controls
      aged 15-82 showed the expected slow loss of such neurons with age. Most (82 +/-
      3.8%) of the pigmented neurons showed immunoreactivity for basic fibroblast
      growth factor (bFGF) and this percentage was unaffected by age. This is in marked
      contrast to the case in Parkinson's disease where only some 12.7 +/- 2.6% of the
      remaining dopaminergic neurons showed bFGF-like immunoreactivity, providing
      further evidence against the hypothesis that Parkinson's disease is due to some
      early insult followed by age-related attrition of the remaining neurons.

PMID- 7804832
TI  - The increase in striatal neuropeptide Y immunoreactivity induced by neonatal
      dopamine-depleting lesions in rats is reversed by intrastriatal dopamine-rich
      transplants.
AB  - The aim of the present experiment was to test whether: (i) the destruction of the
      dopaminergic meso-telencephalic pathway in neonatal rats induces an increase in
      the density of Neuropeptide Y immunoreactive (NPY-IR) neuronal perikarya within
      the denervated neostriatum; (ii) embryonic dopaminergic neurons grafted into the
      neonatal neostriatum could block such an effect of the lesion. As a control,
      density of NPY-IR neurones was also examined in rats lesioned and/or grafted at
      adulthood. The ascending dopaminergic system of 3-day-old rat pups or adult rats
      was unilaterally lesioned by intrahypothalamic injection of 6-hydroxydopamine.
      Grafting was performed six days later. The neonatal lesion increased the number
      of NPY-IR neurones on the lesioned side by 24% as compared to the contralateral
      neonstriatum. This increase was abolished in the neostriatum bearing dopaminergic
      grafts as evaluated six weeks after grafting. These effects are similar to that
      observed in animals lesioned and/or grafted as adults and further extend the
      range of post-lesion modifications which can be reversed by the implantation of
      embryonic DA neurones to neonates.

PMID- 7804833
TI  - Concentration dependence of adenosine and the protection of rat cortical neurones
      during anoxia.
AB  - Aglycaemic/anoxic slices of rat olfactory cortex lose all electrical activity. On
      reoxygenation, 10 microM adenosine enhanced recovery from 23 +/- 7% to 53 +/-
      12%; an increased tissue endurance of 5-7 min. 100 microM adenosine slightly
      depressed recovery to 11.5 +/- 2.1%. Dipyridamole increased whereas adenosine
      deaminase reduced recovery. These observations question the therapeutic
      effectiveness of high adenosine concentrations.

PMID- 7804834
TI  - Cyclic AMP-dependent modulation of interleukin-1 receptors in the mouse AtT-20
      pituitary tumor cell line.
AB  - Previous studies have demonstrated an upregulation of interleukin-1 (IL-1)
      receptors following treatment of mouse AtT-20 pituitary tumor cells with
      corticotropin-releasing factor (CRF). In the present study, we determined the
      modulation of IL-1 receptors and adenylate cyclase activity in AtT-20 cultures
      following treatment with CRF, isoproterenol, forskolin, somatostatin and
      dexamethasone. CRF, isoproterenol and forskolin dose-dependently increased cAMP
      production and [125I]IL-1 alpha binding. In contrast, somatostatin and
      dexamethasone significantly inhibited CRF-stimulated cAMP production and
      decreased both basal and CRF-mediated increases in [125I]IL-1 alpha binding.
      Parallel modulation of IL-1 receptors by agents that stimulate (CRF,
      isoproterenol and forskolin) or inhibit (somatostatin) cAMP production in AtT-20
      cells suggest the importance of this second messenger in regulating IL-1
      receptors.

PMID- 7804835
TI  - Restraint stress increases corticotropin-releasing hormone mRNA content in the
      amygdala and paraventricular nucleus.
AB  - Corticotropin-releasing hormone (CRH) neurons located in the paraventricular
      nucleus (PVN) of the hypothalamus are implicated in regulating the endocrine
      response to stress. The amygdala is an established component of the neural
      circuitry mediating the stress response. To obtain information concerning the
      effects of stress on amygdala CRH neurons, a time-course study was conducted to
      examine, in rats, whether a 1-h restraint period increases CRH mRNA levels. The
      effects of restraint were also measured in the PVN. Using a sensitive RNase
      protection assay, we found that CRH mRNA levels in both the amygdala and
      paraventricular nucleus were significantly elevated 1 h after cessation of
      restraint. CRH mRNA levels in the paraventricular nucleus, but not the amygdala,
      remained elevated at the 3-h post-stress interval. 48 h after the termination of
      restraint, CRH mRNA levels in both brain structures returned to control levels.
      These data provide the first direct evidence that stress activates amygdala CRH
      neurons.

PMID- 7804836
TI  - Decreased GABA immunoreactivity in spinal cord dorsal horn neurons after
      transient spinal cord ischemia in the rat.
AB  - The number of GABA-like immunoreactive (LI) cells in lamina I-III of the rat
      spinal cord was significantly decreased bilaterally 48-72 h after photochemical
      induction of transient spinal cord ischemia compared to sham-operated controls.
      No significant changes in the number of GABA-LI cells were observed at cervical
      level. The number of GABA-LI cells was restored 2 weeks after ischemia. These
      data, together with recent behavioral and electrophysiological findings, suggest
      that decreased intraneuronal GABA levels after spinal cord ischemia may underlie
      the development of the temporary pain-like response to innocuous mechanical
      stimuli (allodynia) in rats after transient spinal cord ischemia.

PMID- 7804837
TI  - Calbindin-D28k immunoreactive neurons form two populations in the rat nucleus
      accumbens: a compartmental study.
AB  - This study shows localisation of a second class of calbindin-D28k containing
      neuron other than the medium-sized spiny neuron in the rat nucleus accumbens,
      using immunohistochemistry with monoclonal antibodies. Ultrastructural
      characteristics were used to identify this second population of accumbens neurons
      within its compartments. Staining with NADPH-diaphorase and calbindin-D28k
      immunoreactivity revealed that some neurons contained both markers.

PMID- 7804838
TI  - Involvement of M2 and non-M2 muscarinic receptors in hippocampal theta rhythm
      induced by carbachol infusion into the septum of the rat.
AB  - Binding and autoradiographic studies have shown the presence of a rather high
      density of M2 muscarinic subtype receptors and the apparent absence or low
      density of the M1 subtype in the septum. We tested the hypothesis that, in the
      urethane-anesthetized rat, septal M2 receptors are involved in the generation of
      the hippocampal theta (theta) rhythm induced by intraseptal administration of
      carbachol, a potent cholinomimetic agent. Carbachol-induced theta was blocked by
      local infusion of the unspecific muscarinic antagonist agent, atropine (20
      micrograms (29.55 nM)), given 10 min prior to carbachol. The intraseptal
      administration of low to high doses of gallamine (range: 20-180 micrograms (22.43
      201.90 nM)), a specific M2 antagonist which displays high affinity for the septal
      region, resulted in significant changes in the electrophysiological
      characteristics of carbachol-induced theta but failed to abolish this rhythm. It
      is suggested that the latter may have resulted from a combined activation of both
      M2 and non-M2 receptors at septal level.

PMID- 7804839
TI  - Chondroitin sulfate proteoglycans are a common component of neuronal inclusions
      and astrocytic reaction in neurodegenerative diseases.
AB  - Previously, we showed three differentially sulfated forms of chondroitin sulfate
      proteoglycans (CSPG) associated with senile plaques, astrocytes and
      neurofibrillary tangles in Alzheimer's disease. Here, monoclonal antibodies were
      used to demonstrate CSPGs in other neurodegenerative diseases. CSPGs were found
      associated with inclusions of Parkinson's, diffuse Lewy body, Pick's diseases,
      and progressive supranuclear palsy. Reacting astrocytes in each of these
      neurodegenerative diseases and Huntington's disease showed immunoreactivity for
      CSPG. CSPG distribution in a variety of neurodegenerative diseases suggests that
      similar mechanisms may be involved in the accumulation of proteoglycans in a
      number of filamentous inclusions.

PMID- 7804840
TI  - Local sprouting of neurites from cultured PC12D cells in response to a
      concentration gradient of nerve growth factor.
AB  - PC12D cells, a subline of PC12 cells, extend neurites very rapidly in response to
      NGF, even when RNA synthesis is blocked. Several minutes after the initiation of
      a concentration gradient of NGF from a micropipette in the vicinity of PC12D
      cells, clear projections emerged from cells on the side facing the micropipette
      while no significant changes in morphology were observed on the other side of
      cells. A control solution administered from a micropipette did not produce any
      changes in morphology. Longer exposure to the gradient of NGF of aggregates of
      PC12D cells increased the length of neurites extending toward the source of NGF.
      The observations indicate that the sprouting of neurites occurs locally in
      regions of PC12D cells that are exposed to an elevated concentration of NGF.

PMID- 7804841
TI  - (+/-) CPP, an NMDA receptor antagonist, blocks the induction of commissural-CA3
      LTP in the anesthetized rat.
AB  - Commissural CA3-CA3 (cCA3) long-term potentiation (LTP) was investigated in the
      anesthetized rat treated with the highly selective NMDA-receptor antagonist D,L
      3[(+/-)-2-carboxypiperazin-4-yl]- propyl-1-phosphonic acid (CPP). Intraperitoneal
      injections of CPP did not significantly affect baseline test responses for either
      field EPSP slope or amplitude measures but did reduce LTP in a dose-dependent
      manner, with 3.2 mg/kg as the lowest effective dose. EPSP variability following
      tetanization was also significantly reduced in both the 3.2 mg/kg and 10.0 mg/kg
      groups. We interpret these results to suggest that a 3.2 mg/kg dose of CPP may be
      sufficient for studying the behavioral effects of this NMDA receptor antagonist.

PMID- 7804842
TI  - Characterization of responses of primary somatosensory cerebral cortex neurons to
      noxious visceral stimulation in the rat.
AB  - In pentobarbital-anesthetized rats, responses of single neurons in primary
      somatosensory cortex (SI) to graded noxious visceral (colorectal distention, CRD)
      and cutaneous stimulation were recorded. One-hundred fifteen SI neurons were
      identified on the basis of spontaneous activity, 66 of which responded to CRD.
      CRD resulted in facilitation of neuronal activity in 33% and inhibition of
      activity in 52% of these cells. Fifteen percent had mixed facilitated/inhibited
      responses to varying CRD pressures. Cutaneous receptive fields were identified in
      71% of CRD-responsive neurons, with low-threshold or wide dynamic range responses
      in most cases. Nearly all cutaneous receptive fields were small contralateral
      sites. Responses to CRD were independent of neuronal depth within the cortex.
      These data support a role of primary somatosensory cerebral cortical neurons in
      visceral nociception.

PMID- 7804843
TI  - A ketamine mixture anesthetic inhibits neuroendocrine and behavioral consequences
      of cocaine administration.
AB  - Cocaine is known to affect different brain systems, particularly those associated
      with arousal, motor and motivational functions. In order to identify a possible
      neurochemical link among these systems, we investigated the effects of the non
      competitive N-methyl-D-aspartate (NMDA) receptor antagonist and dissociative
      anesthetic, ketamine (as a mixture with the sedatives acepromazine and xylazine)
      on the secretion of pituitary adrenocorticotropin hormone (ACTH) and on the
      development of behavioral sensitization induced by cocaine. Pretreatment with the
      ketamine anesthetic mixture (1.6 ml/kg; s.c.) completely blocked the stimulation
      of ACTH by cocaine (5 mg/kg, i.v.; administered 30 min after the ketamine
      mixture) without interfering with ACTH secretion induced by exogenous
      corticotropin-releasing factor (CRF; 5 micrograms/kg; i.v.) or interleukin-1 beta
      (IL-1 beta; 100 ng/kg; i.v.). Administration of the ketamine mixture prior to
      each of five repeated cocaine injections (15 mg/kg; i.p.) also completely
      reversed the behavioral sensitization observed in saline-treated control animals.
      Administration of the anesthetic mixture did not appear to impair the dopamine
      (DA) re-uptake blocking properties of cocaine in the nucleus accumbens since
      substantial increases in extracellular DA were observed in the presence of the
      ketamine mixture. In addition to the present results, no behavioral sensitization
      was also observed in rats anesthetized with a different general anesthetic
      (pentobarbital, 50 mg/kg) under similar conditions to that of the ketamine
      mixture. Taken together, these results are in accordance with the hypothesis that
      stimulation of excitatory amino acid receptor function may be just one of the
      mechanisms whereby cocaine exerts its effects on neuroendocrine and behavioral
      activating systems.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7804844
TI  - Depolarization or glutamate receptor activation blocks apoptotic cell death of
      cultured cerebellar granule neurons.
AB  - Cerebellar granule neurons can be readily maintained in culture if depolarized
      with high concentrations of K+ or subtoxic concentrations of various excitatory
      amino acids. We now report that these depolarizing stimuli promote cerebellar
      granule neuron survival by blocking their programmed death via apoptosis.
      Cerebellar granule neurons maintained in depolarizing conditions and then changed
      to non-depolarizing conditions, exhibit the morphological and biochemical
      features of apoptosis, including cytoplasmic blebbing, condensation and
      aggregation of nuclear chromatin and internucleosomal DNA fragmentation.
      Inhibitors of RNA or protein synthesis greatly attenuate cell death induced by
      non-depolarizing culture conditions. In contrast, cerebellar granule neurons,
      when exposed to fresh serum-containing medium or to high concentrations of
      glutamate, exhibit a delayed-type of neurotoxicity which is non-apoptotic in
      nature. Given the actions of excitatory amino acid receptor agonists in
      preventing apoptosis of cultured cerebellar granule neurons, we hypothesize that
      the functional innervation of postmigratory granule neurons during cerebellar
      development may prevent further elimination of these neurons by blocking their
      programmed death.

PMID- 7804845
TI  - Momentary analgesia produced by copulation in female rats.
AB  - To assess possible changes in nociception during copulation in estrous rats,
      electric shocks that were 20% suprathreshold for eliciting vocalization in
      response to tail shock (STS), were applied to the tail before the initiation of
      copulation and, thereafter, coincident with the onset of mounting bouts by the
      male (Experiment 1). Females vocalized significantly less during non-intromittive
      mounts (M; P < 0.001), intromissions (I; P < 0.001), and ejaculation (E; P <
      0.01) than before the initiation of copulation. In order to assess the importance
      of vaginal stimulation (VS) by penile insertion during mating, in Experiment 2
      30% STS were applied 300-400 ms after the initiation of mounting to ensure that
      the stimuli fell within the period of penile insertion occurring during I and E.
      M failed to significantly inhibit vocalizations to 30% STS. By contrast, both I
      and E markedly inhibited vocalizations in response to STS. This effect was
      transitory since subjects (Ss) vocalized to nearly all 30% STS when delivered 15
      s after I or E. Copulatory analgesia (CA) was abolished by the bilateral
      transection of the pelvic and hypogastric nerves but not by the transection of
      the pudendal nerve (Experiment 3). The magnitude of CA was calibrated by
      determining the doses of morphine sulfate (MS) required to produce similar
      decrements in vocalization to STS. The analgesic effects of I and E were
      equivalent to more than 10 mg/kg and 15 mg/kg, respectively, of MS (Experiment
      4). Pelvic-hypogastric neurectomy, but not pudendal neurectomy, also
      significantly reduced the effect of VS on facilitating lordosis, inducing
      immobilization and hind leg extension, and blocking the withdrawal reflex to foot
      pinch (Experiment 5).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7804846
TI  - Behavioral and pharmacological modulation of ventral tegmental dendritic dopamine
      release.
AB  - The mesocorticolimbic dopamine (DA) system is thought to comprise part of a
      neural substrate participating in behavioral reinforcement. While much emphasis
      has been placed on mesolimbic terminal field activity, the existence of
      somatodendritic DA release has also been established. In the present study, the
      release of endogenous DA from the ventral tegmental DA cell body region of freely
      moving rats was measured, using in vivo chronoamperometry after presentation of
      several environmental stimuli. While presentation of a 9-s moderately intense
      light stimulus did not significantly modify DA release, palatable food
      presentation (FD), 3 min of social interaction (SI) with another male rat and a 3
      min tail-pinch (TP) produced an increase in electrochemical signal, suggesting an
      increase in somatodendritic DA release. Mean peak signal increases (calibrated in
      nM DA concentration) were 104, 135 and 161 nM after FD, SI and TP stimulus,
      respectively. After daily presentation of all four stimuli, one of four DA active
      drugs was given s.c. When compared with preinjection baseline, apomorphine (APO)
      caused a decrease while nomifensine (NOMI), cocaine (COC) and haloperidol (HALO)
      caused an increase in electrochemical signal. When TP was given 30 min after drug
      injection, APO, NOMI and COC suppressed the TP-induced signal increase compared
      with the predrug response. HALO, on the other hand, did not alter TP-induced DA
      release. These data support the hypothesis that the cells of origin of the
      mesocorticolimbic system release dendritic DA after physiologically relevant
      stimuli.

PMID- 7804847
TI  - Effects of adrenalectomy on spatial memory performance and dentate gyrus
      morphology.
AB  - Adrenalectomy (ADX) causes neuronal degeneration and cell loss in the dentate
      gyrus (DG) of the hippocampus. Since chemical or mechanical lesions of the DG are
      associated with impairments of spatial memory in rats, the effects of ADX on
      radial arm maze performance were evaluated. During 15 trials, where all 8 arms of
      the maze were baited, ADX rats were significantly impaired compared to sham
      operated controls (Shams). These trials were conducted 21-42 days post-ADX.
      Following these trials, time delays were instituted between the 4th and 5th
      choices, and ADX rats continued to show impaired performance. Daily intake of 3%
      saline was monitored in all rats and serum corticosterone (Cort) was measured.
      Saline consumption (ml/day) was higher in the ADX group (16.9 +/- 1.6 in ADX vs.
      1.3 +/- 0.3 in Shams) and was negatively correlated with Cort level. Serum Cort
      (% microgram) differed between groups (0.6 +/- 0.4 vs. 15.0 +/- 2.3) and was
      negatively correlated with a greater number of maze errors, a measure of impaired
      performance. Cross sectional DG area was not reduced in ADX rats, and pyknotic
      cell number did not differ significantly between ADX and Sham animals. Moreover,
      pyknotic cell counts did not correlate with behavioral measures. These results
      lead to two conclusions: First, the recovery of accessory adrenal tissue in ADX
      rats, as indicated by the low levels of Cort, appears sufficient to suppress
      dentate granule neuron pyknosis, but may not be sufficient to suppress salt
      appetite.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7804848
TI  - The role of beta1 and beta2 adrenoceptors in isoproterenol-induced drinking.
AB  - The present study examined the contribution of beta1 and beta2 adrenoceptor
      activation to drinking behavior and the stimulation of plasma renin activity
      produced by the mixed beta adrenoceptor agonist, isoproterenol. The stimulation
      of drinking by beta adrenoceptor activation could occur via two independent
      pathways; by either directly stimulating renal beta1 adrenoceptors on the
      juxtaglomerular cells to release renin or by stimulating vascular beta2
      adrenoceptors that would decrease blood pressure and activate afferent neural and
      humoral mechanisms. Selective pharmacological antagonism of each adrenoceptor
      type was achieved by administering atenolol (2.5 mg/kg), a beta1 adrenoceptor
      antagonist, or ICI 118,551 (1 mg/kg), a beta2 adrenoceptor antagonist, before
      treatment with isoproterenol (25 micrograms/kg). Neither adrenoceptor mechanism
      alone could account for all of the water intake or stimulation of plasma renin
      activity due to isoproterenol treatment. Cardiovascular recordings confirmed the
      selectivity of the antagonists to their respective receptor subtypes, with
      atenolol blocking the beta1 adrenoceptor-mediated heart rate increases and ICI
      118,551 blocking the beta 2 adrenoceptor-mediated depressor response to
      isoproterenol. The results provide evidence that the stimulation of both beta1
      and beta2 adrenoceptors by isoproterenol acts in a synergistic manner to induce
      drinking and renin-angiotensin system activation.

PMID- 7804849
TI  - Intracellular free Ca2+ in dissociated cells of the chick pineal gland:
      regulation by membrane depolarization, second messengers and neuromodulators, and
      evidence for release of intracellular Ca2+ stores.
AB  - The regulation of intracellular free Ca2+ concentration was examined in single
      dissociated chick pineal cells using the fura-2 technique. Approximately 10% of
      cells examined exhibited spontaneous Ca2+ oscillations while the rest were
      quiescent. Application of salines containing 80 mM KCl evoked large increases in
      intracellular free Ca2+ that were dependent upon external Ca2+ ions. These
      responses were inhibited by 10 microM nifedipine indicating involvement of L-type
      Ca2+ channels. Application of the tumor promoter thapsigargin (2 microM) evoked
      increases in intracellular free Ca2+. These responses could be observed in the
      absence of external Ca2+ indicating mobilization of internal stores. In the
      absence of external Ca2+, the responses to thapsigargin gradually decayed due to
      depletion of internal Ca2+ pools. A subsequent exposure to saline containing 5.8
      mM CaCl2 caused a rapid increase in intracellular Ca2+ that was consistently
      larger than the peak response to thapsigargin. Application of 100 nM vasoactive
      intestinal peptide (VIP), a neurohormone that stimulates melatonin secretion from
      pineal cells, induced a sustained increase in intracellular free Ca2+ in a
      subpopulation of cells. In a small number of cells, VIP evoked Ca2+ oscillations.
      Approximately half of the cells examined showed no response to VIP. Application
      of 200 microM norepinephrine, which inhibits melatonin secretion from the chick
      pineal, had no effect on intracellular free Ca2+ in any quiescent or
      spontaneously oscillating cells. Application of 5 mM 8-Br-cAMP evoked sustained
      increases in intracellular Ca2+. Similar effects were obtained with the
      phosphodiesterase inhibitors papaverine (50 microM) or isobutylmethylxanthine
      (100 microM). Application of 200 nM forskolin, an activator of adenylate cyclase,
      evoked increases in intracellular free Ca2+ that could be detected in the
      presence of 10 microM nifedipine. The responses to forskolin gradually decayed in
      Ca(2+)-free external salines due to depletion of intracellular Ca2+ stores.
      Subsequent exposure to external Ca2+ caused a rapidly developing increase in
      intracellular Ca2+ that was larger than the peak response to forskolin. These
      results indicate that the regulation of intracellular free Ca2+ in chick pineal
      cells is complex. These cells exhibit Ca2+ oscillations and can mobilize both
      external and internal Ca2+ pools. Agents that increase intracellular cAMP cause
      mobilization of internal Ca2+ stores, possibly secondary to effects on other
      second messenger systems. Chick pineal cells, like many other cell types, possess
      mechanisms to allow for refilling of depleted internal Ca2+ stores. These results
      suggest new mechanisms for the regulation of melatonin synthesis and secretion
      and possible sites of action for the intrinsic circadian oscillator.

PMID- 7804850
TI  - Concentrations and distribution of vasoactive intestinal peptide (VIP), peptide
      histidine isoleucine (PHI) and peptide histidine valine (PHV) in the cerebral
      cortex and the suprachiasmatic nucleus of the mouse.
AB  - Prepro-vasoactive intestinal peptide (prepro-VIP) is processed to at least three
      biologically active peptides: VIP, peptide histidine isoleucine (PHI) and an
      extended PHI, peptide histidine valine (PHV). The aim of the present
      investigation was by chromatography combined with RIA and immunocytochemistry to
      determine which of these peptides were present in the cerebral cortex and the
      hypothalamic suprachiasmatic nucleus (SCN) of the mouse. These regions were
      chosen since they are known to contain a high concentration of VIP but the
      relative concentration of PHI and PHV is not known. Tissue was extracted and
      subjected to gel chromatography and high-pressure liquid chromatography (HPLC).
      VIP and PHI immunoreactivities co-eluted with synthetic rat VIP and PHI. A minor
      peak of PHI and prepro-VIP(111-122) immunoreactivities eluted at the position of
      synthetic PHV. Surprisingly, a major peak of prepro-VIP(111-122) immunoreactivity
      eluted in a position not related to any other immunoreactivity indicating the
      presence of prepro-VIP(111-122). Measurements of these immunoreactivities in
      cortical and suprachiasmatic extracts revealed that VIP was found in the highest
      concentration whereas PHV was found in the lowest. Immunoreactivity for PHI and
      prepro-VIP(111-122) was found in moderate concentrations. Except for prepro
      VIP(111-122) which was found to be approximately 3 x higher concentrated in the
      SCN than in the cerebral cortex, the other immunoreactivities were found in
      almost similar relative concentrations in the two tissues. Using
      immunocytochemistry, elongated neurons mostly of the bipolar type with prominent
      processes observed in the cerebral cortex reacted with all antisera tested. More
      PHI/PHV/prepro-VIP(111-122)- than VIP-immunoreactive (ir) nerve fibers were found
      in the cerebral cortex. In the SCN, the density of immunoreactivity was the same
      whatever antiserum used. VIP-, PHI- and prepro-VIP(111-122)/PHV-ir neurons were
      observed in the ventral part of the nucleus with numerous axons coursing
      caudodorsally into the subparaventricular area. A substantial number of terminals
      was detected caudal to the paraventricular nucleus. Minor projections spread to
      the medial part of the anterior nucleus and to the medial preoptic area
      hypothalamic. These data show that VIP and PHI are the major active peptides
      derived from prepro-VIP in the mouse cerebral cortex and SCN whereas PHV was
      found in minor concentrations. Prepro-VIP(111-122), which so far has been found
      to have no functional significance, is, therefore, most likely a vaste fragment
      of processing of PHI in central neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7804851
TI  - Flexible endoscopes in treatment of colloid cysts of the third ventricle.
AB  - Goals of treatment of colloid cysts of the third ventricle are relief of
      foraminal obstruction and prevention of recurrence. Both goals are perfectly met
      by microsurgical removal from a transfrontal-transventricular or a transcallosal
      approach, however, with both approaches there are serious related complications.
      CT-guided stereotactic aspiration of colloid cysts is a simple method with low
      risk. Nevertheless, treatment failures as well as a considerable late recurrence
      rate are reported. The CT-guided stereotactic endoscopic technique gives the
      opportunity to widely open the cyst wall and aspirate the cyst fluid under direct
      visual control, thereby reducing the risk of the procedure and due to broad
      opening of the cyst wall refilling becomes less likely possible.

PMID- 7804852
TI  - Stereotactic and ultrasound guided minimal invasive surgery of subcortical
      cavernomas.
AB  - The experience of 7 operated patients with cavernous haemangiomas (CHa) and of 2
      conservatively treated older patients is reported. There was no further
      postoperative neurological deficit, although 6 of the 7 patients had the CHa in
      an eloquent cerebral region. Two of the operated patients (22%) had several
      bleedings before surgery. In these cases seizures and visual field deficits
      remained. The relatively low rate of complications in our patient group was
      possible because an exact preoperative localisation helped to avoid a large
      traumatisation. This is possible with a stereotactic system or directly by CT
      guided skin marking. Intraoperative ultrasound was necessary in all cases because
      there was no landmark at the cerebral surface. The CHa was removed by a
      transsulcal microsurgical operation. A complete removal of the surrounding
      haemosiderin rim around the angioma seems necessary to avoid further seizures.
      The used technique has proved to be a simple and safe minimal invasive method.

PMID- 7804853
TI  - Endoscopic procedures through the foramen interventriculare of Monro under
      stereotactical conditions.
AB  - The foramen interventriculare of Monro is an anatomical narrowness for the
      endoscopic access to the third ventricle. The effective mechanical angle to pass
      the foramen interventriculare from a frontal bore hole depends on the diameter in
      the plane of entrance, the depth of the foramen, and the diameter of the
      endoscope. Under the pathological conditions of a hydrocephalus internus the
      foramen interventriculare is enlarged. By means of stereotactical guidance, it is
      possible to reach the third ventricle accurately without damaging anatomical
      structures around the foramen interventriculare. The endoscopic technique under
      stereotactical guidance using a rigid endoscope is sufficient and safe to perform
      ventriculostomies in cases of hydrocephalus occlusus. Best clinical results were
      obtained in patients with benign aqueduct stenosis or with a tumor in this region
      compressing the aqueduct. In all patients no further shunt operation was
      necessary. The path through the foramen interventriculare should be considered
      also for biopsies in the third ventricle. Calculation of the foramen
      interventriculare trajectory prevents perforation of the roof of the third
      ventricle containing the main deep veins. Lesions in the foramen
      interventriculare like colloid cysts can also be approached very accurately by
      means of stereotactical calculation. However the endoscopic technique with the at
      present obtainable instruments does not allow removal of the whole lesion. Even
      so a free passage to the third ventricle can be achieved by reducing the size of
      the cyst by means of coagulation and sucking off the colloid material.

PMID- 7804854
TI  - Microstructure technologies and their potential in medical applications.
AB  - One of the major fields of application of microstructure technology and
      microsystems technology will probably be centered in medical engineering. Above
      all in neurosurgery, highly sophisticated surgical instruments featuring high
      functionality combined with high reliability are needed. Products fabricated by
      conventional manufacturing technologies can fulfill these demanding requirements
      only to a limited extend. At the Karlsruhe Nuclear Research Center first
      prototype components such as microspectrometers, microturbines and microfluidics
      structures are presently fabricated and tested which can be used in future
      microendoscopes as sensors or actuators. Combined with adequate information
      processing and suitable interface technology, it will be possible to create
      microsystems for various medical applications.

PMID- 7804855
TI  - The current status of endoscopic third ventriculostomy in the management of non
      communicating hydrocephalus.
AB  - Improvements in the technology have made endoscopic third ventriculostomy safer
      than earlier technics of open third ventriculostomy as described by Scarf (14).
      Similarly, it is safer than the stereotactic technics used by Pierre-Kahn (10),
      Sayers (13), and Hoffman (4). The morbidity and mortality have decreased and the
      effectiveness has also increased (12, 15). Modern operations are based on Guiot's
      technique (2). In the management of hydrocephalus third ventriculostomy has to be
      compared with the treatment with intracranial shunts. Currently in our hands the
      procedure has a higher morbidity rate than a shunt operation. Our figures include
      those from our early experience (5)--more recent figures show a lower
      complication rate. We believe the higher morbidity is acceptable as the chance of
      being permanently cured is 80% in favourable cases.

PMID- 7804856
TI  - Superolateral approach to orbital tumors.
AB  - The conventional lateral approach to the orbit (Kronlein) does not allow a
      satisfactory view of the superior part of the orbit and the operative field is
      rather narrow. Therefore, large tumors which have developed not only laterally
      but also superiorly are usually approached transcranially. The craniotomy and
      exposure of the dura may be avoided when the tumor does not extend too far
      posteriorly and medially, by turning a larger orbital bone flap than the
      Kronlein's one. This technique was described by Nakamura as "type I orbitotomy"
      and can be referred to as a superolateral approach. After a bicoronal skin
      incision, a free orbital bone flap is cut. It includes the lateral orbital rim, a
      large external part of the superior orbital rim, and the lateral orbital wall.
      From 1985 to 1990 this approach was performed on 23 patients presenting with
      lacrimal gland tumors in 14 cases (11 pleomorphic adenomas, 2 adenoid cystic
      carcinomas, 1 adenocarcinoma), schwannomas in 2 cases, dermoid cyst in 1 case,
      hydatic cyst in 1 case, cavernous hemangiomas in 2 cases, inflammatory
      pseudotumor in 1 case, and mucoceles in 2 cases. This superolateral approach
      provides a wider exposure to the superolateral orbit than the classical
      Kronlein's approach and avoids the drawbacks of a craniotomy. A direct incision
      through the eyebrow can be used for bald people or for patients in poor
      condition.

PMID- 7804857
TI  - Road rage.

PMID- 7804859
TI  - Hypothermia.
AB  - Hypothermia may present to any department at any time. It may present as a
      primary or secondary illness and if not detected, and/or managed appropriately,
      treatment of other concurrent illnesses and patient survival may be severely
      compromised. This paper will endeavour to assist the nursing and medical staff of
      Accident and Emergency (A & E) departments to recognise and classify hypothermia.
      It will discuss the pathophysiology associated with heat loss and heat gain, and
      the implementation of appropriate management. The survival of the hypothermia
      patient is greatly dependent on several factors: method of rewarming, severity of
      hypothermia, duration prior to treatment, degree of hypotension, and severity of
      underlying disease (this being the most likely determinant of survival).

PMID- 7804858
TI  - A cautionary tale.

PMID- 7804860
TI  - Child accident prevention as a health promotion issue--how extensive is the
      problem and how far have A & E departments responded to the recommendations made?
AB  - Accidents to children are always a source of concern to any health care
      professional. Despite the wealth of evidence that suggests many of these
      accidents are preventable, the numbers of deaths and long-term disability have
      remained fairly constant. It would appear that only if all agencies and
      authorities who have a responsibility for the health and safety of children work
      closely together, to educate those caring for children, enforce legislation and
      pressure governments to improve the child's environment, will a dramatic
      reduction in accidents be achieved. Despite this, the Health of the Nation
      document looks solely towards an educational approach aimed at the general public
      with no apparent thought as to the effectiveness of this strategy.

PMID- 7804861
TI  - Assessing humanitarian needs--Afghanistan.
AB  - During 5 weeks of 1993, 10,000 people were wounded and over 800 killed in Kabul,
      capital city of Afghanistan. 50,000 refugees have fled Kabul for the countryside,
      or the safety of Pakistan. In the Bosnian conflict 55,000 people have been
      injured over the past 2 years. At the present rate, Kabul will reach this total
      within 6 months. My brief in Kabul was to visit as many hospitals and polyclinics
      as possible, talk to the staff, and find out whether there is a need for MERLIN
      (Medical Emergency Relief International) to intervene in this area. This
      intervention would be in the form of a short mission of 3-4 months duration,
      deploying a trauma team, immunisation programme or supplies facility. It was
      essential to assess the trauma facilities and document what supplies and staff
      were needed.

PMID- 7804862
TI  - Trauma teams vs non-trauma teams.
AB  - This paper gives an overview of research which analysed the nurse's role in the
      UK trauma team. A prospective study was carried out of 100 trauma patients in 6
      UK Accident and Emergency (A & E) departments. The patients were observed
      throughout their time in the department and the time taken to assess and
      resuscitate them was monitored along with the structure and organisation of the
      team. The results revealed that in departments where no trauma teams were present
      25% of the patients did not have a secure airway during their stay in the A & E
      department, and 18% of patients did not have any intravenous access. In
      comparison, departments with teams secured the airway and obtained intravenous
      access in 100% of the cases observed. The results highlighted that a structured
      organised team, with predetermined roles and responsibilities for both nursing
      and medical staff, has a direct bearing on patient outcome.

PMID- 7804863
TI  - Moving around Europe--an overview of European Union nursing legislation.
AB  - Making sense of the European Union (EU) and its institutions rests largely on the
      understanding that essentially all its endeavours are an attempt to guarantee the
      four freedoms of movement--of goods, services, labour and capital--that are the
      pre-requisites for the creation of an economic area without internal frontiers
      and the establishment of economic and social union. With the ratification of the
      Treaty on European Union (Maastricht Treaty) the EU also aims to assert its
      identity on the international scene; strengthen the protection of the rights and
      interests of the nationals of its Member States; develop close cooperation on
      justice and home affairs; and maintain in full the acquis communautaire (the
      evolving legacy of EU developed principles and laws). It is the four freedoms of
      movement, however, that remain the dynamo that drives EU thinking. To disregard
      this fundamental concept is to ensure that the EU will for ever remain a mystery.

PMID- 7804864
TI  - Nurse-patient communications.
AB  - Every day the Accident and Emergency nurse is challenged to listen and talk to
      suicidal patients, to try and encourage a distressed and battered wife or is
      asked to give advice and respond to seemingly endless questions. To give
      effective care, the awareness of the importance of such communications by
      Accident and Emergency nurses needs to be increased. This paper attempts to give
      a brief overview of verbal and non-verbal communications and the importance of
      interpersonal skills in our aim to achieve excellence in care.

PMID- 7804865
TI  - A response to Walsh's study of the attitudes of A&E staff towards patients (A&E
      Nursing 2 (1): 27-32)

PMID- 7804866
TI  - A forgotten need: paediatric resuscitation training.
AB  - This article highlights the fact that there are currently no real official
      recommendations regarding the provision of paediatric resuscitation training in
      the UK. All too often, this teaching features as no more than an 'add on' to
      adult resuscitation sessions. This is a thoroughly inadequate situation as the
      relatively infrequent occurrence and different aetiology of paediatric arrests
      necessitates specific training, based on standard guidelines, and adapted to meet
      the needs of the various groups who have contact with children. A three-tiered
      package of training is recommended, starting with nationwide paediatric Basic
      Life Support (BLS) training for the general public. In addition to BLS,
      healthcare personnel need to be trained in appropriate use of airway adjuncts.
      Paediatric Advanced Life Support (ALS) is also essential for all medical, nursing
      and paramedical staff who come into contact with acutely-ill children. In an
      attempt to address the need for ALS, the PALS (Paediatric Advanced Life Support)
      course, has been implemented in the UK. Adapted from the American PALS course, it
      aims to provide appropriate personnel with a systematic, research-based approach
      to acutely-ill children in emergency situations.

PMID- 7804867
TI  - The season of goodwill.

PMID- 7804868
TI  - Children and the accident and emergency department.
AB  - It is not unusual for children to come into the Accident and Emergency (A & E)
      department unaccompanied by their parents and alone or with other children. At
      the one extreme there might be a child who is bleeding from a cut which requires
      urgent stitching, at the other extreme, there may be a road traffic accident
      where the child is unconscious and no one initially knows his name or parents and
      address. What is the legal situation regarding the duty of the A & E staff? This
      article starts with the general principles relating to consent to treatment and
      then looks at specific situations relating to children.

PMID- 7804869
TI  - Examining equipment for wound care: the use of forceps and cotton wool in
      dressing packs.
AB  - Wound care experts have, over recent years, questioned the routine use of forceps
      and cotton wool balls in packs used for cleansing and dressing wounds. Despite
      relevant research supporting this view, these items still appear in wound care
      packs in some hospitals and the basis for this practice, at times, does not seem
      to have been questioned. A project to explore the effect of introducing a new
      pack (substituting gloves and non-woven gauze for cotton wool and forceps) was
      undertaken at St James's University Hospital in the summer of 1993. Nurses'
      opinions regarding satisfaction with the new pack were explored along with
      whether they would prefer to use forceps. Results showed that the majority of
      nurses were satisfied with the new packs and found them an appropriate,
      acceptable alternative. The Accident and Emergency findings are reported with a
      discussion of the implications for practice.

PMID- 7804871
TI  - Further improvement in methods of group-to-group sequence alignment with
      generalized profile operations.
AB  - It has previously been shown that rigorous optimization of alignment between two
      groups of sequences in the sense of minimal sum of pairs (SP) score with a linear
      gap-weighting function can be achieved by an extended version of the dynamic
      programming algorithm. The major drawback of this algorithm was that the
      computation time grows in proportion to the product of the numbers (M and N) of
      sequences comprising the two groups. A new algorithm presented in this paper
      achieves the same rigorous alignment in a time complexity much less dependent on
      the sizes of the groups. Examinations with many groups of sequences indicated
      that the new algorithm runs faster than the earlier one when M x N > 6-10,
      approximately 10 times faster when M x N approximately 200, and > 100 times
      faster when M x N > 2500. This computational acceleration facilitates application
      of the algorithm to alignment of large groups, especially in the framework of
      iterative refinement strategies.

PMID- 7804870
TI  - SORTEZ: a relational translator for NCBI's ASN.1 database.
AB  - The National Center for Biotechnology Information (NCBI) has created a database
      collection that includes several protein and nucleic acid sequence databases, a
      biosequence-specific subset of MEDLINE, as well as value-added information such
      as links between similar sequences. Information in the NCBI database is modeled
      in Abstract Syntax Notation 1 (ASN.1) an Open Systems Interconnection protocol
      designed for the purpose of exchanging structured data between software
      applications rather than as a data model for database systems. While the NCBI
      database is distributed with an easy-to-use information retrieval system, ENTREZ,
      the ASN.1 data model currently lacks an ad hoc query language for general-purpose
      data access. For that reason, we have developed a software package, SORTEZ, that
      transforms the ASN.1 database (or other databases with nested data structures) to
      a relational data model and subsequently to a relational database management
      system (Sybase) where information can be accessed through the relational query
      language, SQL. Because the need to transform data from one data model and schema
      to another arises naturally in several important contexts, including efficient
      execution of specific applications, access to multiple databases and adaptation
      to database evolution this work also serves as a practical study of the issues
      involved in the various stages of database transformation. We show that
      transformation from the ASN.1 data model to a relational data model can be
      largely automated, but that schema transformation and data conversion require
      considerable domain expertise and would greatly benefit from additional support
      tools.

PMID- 7804872
TI  - A global approach for contig construction.
AB  - A program for assembling sequences by using a global approach has been developed.
      By successive steps, a more and more precise classification of DNA fragments
      permits the positioning of the sequences on the contig; after having detected the
      pairs of overlapping sequences, groups are formed such that all sequences in a
      group overlap. Sequences common to several groups enable the groups to be ordered
      in a series. Ambiguities in the order of groups can arise at this stage, due to
      the presence of repeated fragments; different solutions are then proposed.
      Putting the groups into order leads to a preclassification of sequences. The
      fragments are then aligned by group, by searching for words common to all
      sequences in the group, and using an algorithm of dynamic programming. A detailed
      example on a set of nine sequences accompanies the description of the method.

PMID- 7804873
TI  - METREE: a program package for inferring and testing minimum-evolution trees.
AB  - The METREE program package for estimating phylogenetic trees with the minimum
      evolution method is written in Turbo C 2.0 and is intended to be used on any IBM
      compatible personal computers that have a mathematical coprocessor. The package
      is simple to use and is menu driven. A program for visualizing and printing out
      the final tree is also included.

PMID- 7804874
TI  - Sequence analysis by electronic mail: a tool for accessing Internet e-mail
      servers.
AB  - A new utility program, MSU, is described that simplifies the use of electronic
      mail servers for sequence analysis. Service descriptions are defined in external
      control files which can be changed without affecting the main program. This
      approach makes MSU a highly flexible tool that allows easy modification,
      extension and customization of service descriptions to suit users' personal
      requirements.

PMID- 7804875
TI  - Multiple sequence alignment using simulated annealing.
AB  - Multiple sequence alignment is a useful technique for studying molecular
      evolution and analyzing structure-sequence relationships. Dynamic programming of
      multiple sequence alignment has been widely used to find an optimal alignment.
      However, dynamic programming does not allow for certain types of gap costs, and
      it limits the number of sequences that can be aligned due to its high
      computational complexity. The focus of this paper is to use simulated annealing
      as the basis for developing an efficient multiple sequence alignment algorithm.
      An algorithm called Multiple Sequence Alignment using Simulated Annealing (MSASA)
      has been developed. The computational complexity of MSASA is significantly
      reduced by replacing the high-temperature phase of the annealing process by a
      fast heuristic algorithm. This heuristic algorithm facilitates in minimizing the
      solution set of the low-temperature phase of the annealing process. Compared to
      the dynamic programming approach, MSASA can (i) use natural gap costs which can
      generate better solution, (ii) align more sequences and (iii) take less
      computation time.

PMID- 7804876
TI  - Computer-assisted restriction mapping: an integrated approach to handling
      experimental uncertainty.
AB  - Building a map of restriction sites from double-digest gel data can be a complex
      and frustrating task, especially when many DNA fragments are detected or when the
      gel results are ambiguous. 'Double Digester' is an interactive, graphical
      computer program which helps researchers understand and resolve such data. It
      explicitly represents the experimental data, the associated uncertainties, the
      researcher's hypotheses and possible map interpretations. Alternative solutions
      are frequently possible, and the differences between them may help determine
      which additional experiments might resolve ambiguities. Initial use has confirmed
      the benefits of this approach, and has suggested ways in which it can be refined
      and extended. Double Digester meets the need for a practical tool to help build
      restriction maps, and also illustrates how a computer-based tool can confront
      experimental uncertainty in an integrated fashion.

PMID- 7804877
TI  - A four-dimensional digital image archiving system for cell lineage tracing and
      retrospective embryology.
AB  - The paper describes a digital image archiving system for time-lapse microscopy.
      The system uses an MS-DOS compatible computer to store video images while
      simultaneously controlling a stepping motor. In a typical experiment, images
      might be taken at 30 s intervals in each of 25 consecutive focal planes. A system
      with 2.5 Gbyte disk capacity can store approximately 18,000 full frame images: 6
      h recording at maximum resolution. Once recorded, images series stored on disk
      can be 'played back' in any order. Generally, images from a single focal plane
      are displayed consecutively in either forward or reverse time. The focal plane
      can be shifted during playback, allowing individual cells to be followed as they
      move between focal planes. To facilitate the annotation and interpretation of the
      real-time images, a mouse-driven interface allows users to define and follow
      individual objects (e.g. cells). The recorded image series can be achieved
      inexpensively using standard digital tape backup hardware. In this laboratory,
      the system has been particularly useful for tracing embryonic cell lineages and
      cell migrations. Detailed system specifications, including source code, compiled
      programs, hardware requirements and users manual are available directly from the
      author or by anonymous FTP (ciw1.ciwemb.edu).

PMID- 7804878
TI  - A computer program for construction of circular restriction maps.
AB  - The computer program COSMAP for construction of circular restriction maps has
      been developed. The generator is based on a permutational algorithm that puts
      forward all the possible maps that can be made with two enzymes, and the
      consistency checker compares the calculated and experimental double-digest
      fragment sizes within a predefined error bound. The output consists of the
      complete set of solutions ordered by a score number that is based on the matching
      degree between experimental and calculated double restriction fragment sizes. The
      program allows the application of heuristic rules which reduces the number of
      permutations to be checked and the number of sound solutions.

PMID- 7804879
TI  - Fast databank searching with a reduced amino-acid alphabet.
AB  - Fast sequence databanks search algorithms generally make use of hash tables and
      look for exactly matching words. An increased sensitivity--at the expense of a
      decreased selectivity--can be attained in the case of proteins by using a reduced
      amino acid alphabet. We propose here an alphabet reduced to 10 symbols, that we
      used in modified versions of the FASTP and SCAN programs. An application to the
      aminoacyl-tRNA synthetases shows that this technique may be useful in detecting
      distant relationships between proteins.

PMID- 7804880
TI  - A note about computing all local alignments.
AB  - A recent paper in this journal by G. Barton proposed an efficient algorithm for
      locating locally optimal alignments between two sequences. Although the paper
      claims that all such alignments are found, the approach frequently fails to
      detect some of the significant matches. This note explains the deficiency.

PMID- 7804882
TI  - The National Museum of Civil War Medicine: building a vision.

PMID- 7804881
TI  - A simple tool to search for sequence motifs that are conserved in BLAST outputs.

PMID- 7804883
TI  - Jonathan A. Letterman, surgeon for the soldiers.

PMID- 7804884
TI  - Beverly Barrett: a civilian doctor in the Civil War.

PMID- 7804885
TI  - The Grand Army of the Republic Memorial Museum.

PMID- 7804886
TI  - Field medicine at Antietam.

PMID- 7804887
TI  - [Incidence and characteristics in identification of abused children: cross
      cultural comparison].
AB  - This study compared the incidence and characteristics of reported child abuse
      cases in two different ethnic groups. Incidence was calculated based on the total
      number of cases (N = 2,854) reported to child protection authorities between July
      17, 1988 and March 31, 1989. In a sample of 953 reports, the following were
      examined: the source of the reporting, type of abuse, substantiation and age of
      the child. The incidence was found to be slightly higher among Haitian group
      compared to French-Canadian group. In the former case, reporting tended to
      originate with public authorities such as the police or school personnel. Cases
      tended to consist mainly of physical abuse, with very few cases of sexual abuse.
      Most involved adolescents. These results suggest that child-rearing practices of
      Haitian families are in conflict with the values of the host community, and that
      there exist similar value-based conflicts between Haitian parents and their
      children.

PMID- 7804888
TI  - Mental retardation and adult women's perceptions of adolescent sexual abuse.
AB  - This study examined the effect of mental retardation and an adolescent girl's
      behavior on adult women's perceptions of sexual abuse and the girl's
      responsibility. Subjects were 288 women, age 18 to 33, who were randomly assigned
      a vignette describing a sexual encounter between an adolescent girl and boy.
      Girl's diagnosis (mentally retarded or nonretarded), boy's diagnosis (mentally
      retarded or nonretarded) and girl's behavior (encouraging, passive, or resisting)
      were experimentally manipulated. Factor analysis of responses yielded three
      factors: girl's responsibility, boy's abusiveness, and parents' responsibility.
      Results indicate that subjects perceive the girl's responsibility differently
      among girls with and without mental retardation. Regardless of her behavior,
      subjects perceive the girl as bearing little responsibility when she is retarded.
      However, when she is nonretarded, she bears more responsibility when she is
      encouraging than when she is passive or resisting, and she bears greater
      responsibility when she is passive than when she is resisting. Also, when the
      girl is encouraging, the boy's perceived sexual abusiveness is less when he is
      mentally retarded than when he is nonretarded. Finally, parents are assigned
      greatest responsibility when the girl is passive, regardless of her diagnosis.

PMID- 7804889
TI  - Preverbal sexual abuse: what two children report in later years.
AB  - This paper details two case studies of preverbal abuse in which children later
      gave detailed accounts of their abuse, indicating that their memories were still
      intact despite lacking sufficient language to report the abuse when it occurred.
      A series of issues about preverbal abuse are discussed while integrating
      cognitive-developmental research about children's early memory: How early can
      children remember? Does memory change with maturity? What effect does trauma have
      on memory? What surfaces early memories? What are the long term effects of very
      early sexual abuse? Implications for practice and prosecution of this early abuse
      are listed.

PMID- 7804890
TI  - The prevalence of child sexual abuse in Finland.
AB  - The prevalence and context of child sexual abuse was surveyed in Finland. A
      random sample of 409 comprehensive school classes with about 9,000 15-year-olds
      were asked to anonymously fill out questionnaires. The majority (93%) filled the
      questionnaires out in the privacy of the school nurse's office, the rest in their
      classrooms. Eighty-nine percent of the selected classes participated in the
      survey and the response rate of the students in those classes was 96%. Eighteen
      percent of girls and 7% of boys reported sexual experiences with a person at
      least 5 years older than themselves at the time of the incident. Voluntary
      experiences with boy or girlfriends were then excluded to get an estimate of the
      prevalence of sexual abuse. About 6-8% of girls and 1-3% (depending on the used
      criteria) of boys reported experiences that could be classified as sexual abuse.
      Force had been used against 2% and violence against 1% of the girls. Regional
      differences were so great both in sexual experience and in sexual abuse that they
      could be interpreted as giving support to a "subculture theory" of sorts. The
      results are compared with prevalence estimates from the United States and the
      Nordic countries.

PMID- 7804891
TI  - The impact of child sexual abuse--a study of a random sample of Norwegian
      students.
AB  - The long-term impact of child sexual abuse (CSA) has most typically been
      concentrated on the psychological outcomes. The aim of the present study was to
      examine the relationship between CSA and self-reported complaints including both
      psychological and psychosomatic problems as well as absenteeism. A random sample
      of 510 female and 486 male students completed a questionnaire that included
      questions about CSA. The overall response rate was 75.3%. A symptom scale was
      constructed by asking the respondents to rate themselves on a three-category
      scale for 13 items concerning both psychological and somatic health problems.
      They were also asked to indicate how many days the problem had caused them to be
      absent from class or work during the year prior to the study. CSA was reported by
      116 of the students (11.7%). CSA was associated with a broad range of health
      problems; including genital pain/infections and headache/abdominal/muscular pain
      as well as psychological disorders such as anxiety and suicidal ideations. A
      linear relationship was demonstrated between the severity of CSA and the symptom
      score, as well as between the severity of CSA and days absent from work.
      Postpubertal onset of abuse and close relationship with the offender were
      positively associated with the number of sick-leave days.

PMID- 7804892
TI  - The interpersonal and psychological functioning of women who experienced
      childhood physical abuse, incest, and parental alcoholism.
AB  - Questionnaires assessing childhood physical abuse (CPA), childhood incest (CI),
      and parental alcoholism (ACOA) were completed by 253 college women from
      introductory psychology classes at a large midwestern university. The
      relationship between these variables and the level of depression, self-esteem and
      involvement with physically abusive, sexually assaultive, sexually coercive, and
      chemically dependent partners was assessed. Support was found for an additive
      model of trauma that predicted a relationship between number of childhood traumas
      and adult outcomes. Limited support was found for a specificity model of trauma
      that predicted that specific childhood trauma would be predictive of parallel
      negative adult outcomes.

PMID- 7804893
TI  - Enhancing multi-agency collaboration in the management of child sexual abuse.
AB  - Conflict naturally occurs when multiple organizations with different mandates
      interact to deliver services to children who have been sexually abused. In this
      article, the authors review the underlying sources of conflict that impair
      interorganization functioning, and dysfunctional techniques used to manage such
      conflict. As an alternative to dysfunctional conflict management strategies, the
      authors develop a model for managing conflict which builds on concepts from the
      operations and negotiations literature. The approach the authors advocate
      involves the three steps of problem characterization, acknowledgement of relevant
      goals and interests, and negotiation when interests are in conflict. The benefit
      of this approach, and difficulties encountered when employing it, are discussed.

PMID- 7804894
TI  - The effect of child physical abuse and neglect on aggressive, withdrawn, and
      prosocial behavior.
AB  - This study investigated aggressive, withdrawn, and prosocial behavior in
      physically abused (N = 21), nonabused-neglected (N = 26), and nonabused
      nonneglected (N = 21) children aged 5 to 8 years. Multiple assessment techniques
      were used, specifically the Human Figure and Kinetic Group Drawings, children's
      verbal stories, and teacher ratings on the Pittsburgh Adjustment Survey Scales.
      All measurement techniques were able to discriminate among the three groups.
      Physically abused children displayed significantly more aggressive behavior than
      the neglected and nonmaltreated; neglected children were significantly more
      withdrawn than the physically abused and nonmaltreated; nonmaltreated children
      exhibited significantly more prosocial behavior than the abused and neglected. No
      single dimension adequately discriminated each of the three groups. Full
      discrimination was achieved only when aggressive, withdrawn, and prosocial
      behavior were combined in a multivariate analysis, indicating that effects of
      maltreatment must be viewed as multidimensional.

PMID- 7804895
TI  - Recall of abuse in childhood and three measures of dissociation.

PMID- 7804896
TI  - Normal versus abnormal genital finding in children: how well do examiners agree?

PMID- 7804897
TI  - Chemoprevention.
AB  - Chemoprevention has been shown to be an extremely promising approach to the
      prevention of invasive cancer. Through the identification of chemopreventive
      agents that inhibit or reverse the process of carcinogenesis, new strategies of
      early intervention can be developed for patients at high risk that potentially
      prevent the onset of invasive and metastatic phases of cancer. This articles
      reviews the present efforts in chemoprevention research, including the
      identification of promising agents, screening, and preclinical and clinical
      evaluations.

PMID- 7804898
TI  - Perspectives on cancer prevention.
AB  - The best way to control cancer is to find means to reduce the risk of cancer. Mr.
      Garfinkel, the former Vice President for Epidemiology and Statistics and Director
      of Cancer Prevention for the American Cancer Society, discusses the ongoing
      research on cancer prevention and suggests that based on the accumulated
      evidence, authoritative groups must now seriously consider making recommendations
      about chemopreventive substances to reduce cancer risk.

PMID- 7804899
TI  - Surgical treatment of colorectal metastases to the liver.
AB  - Up to one fourth of patients diagnosed with colorectal cancer present with liver
      metastases, and by the time of death, up to 70 percent of patients with
      colorectal cancer have metastatic disease to the liver. At present, surgical
      excision is the standard therapy for resectable liver metastases from colorectal
      primaries. This article reviews the natural history of colorectal metastases to
      the liver and results of studies of systemic chemotherapy, surgical resection,
      and alternative surgical approaches.

PMID- 7804900
TI  - Cancer pain management: corrections and comments.

PMID- 7804901
TI  - Cancer pain management: corrections and comments.

PMID- 7804902
TI  - Federation for International Cooperation of Health Services and Systems Research
      Centers (FICOSSER). Third general conference. Helsinki, Finland, 6-9 July 1994.
      Abstracts.

PMID- 7804903
TI  - Correct use of the EnviroAmp PCR Legionella kit.

PMID- 7804904
TI  - Construction of composite transposons for halophilic Archaea.
AB  - Transposons with selectable marker genes (e.g., antibiotic resistance) have been
      extremely useful tools in bacterial genetics but have not been found naturally in
      Archaea. We constructed synthetic transposons consisting of halobacterial ISH
      elements (ISH2, ISH26, or ISH28) flanking a mevinolin resistance determinant.
      Introduction of these constructs into Haloferax volcanii cells can produce drug
      resistant transformants through homologous recombination between the plasmid hmgA
      gene and the chromosomal hmgA locus. This problem was overcome by using another
      host, Haloarcula hispanica, the hmgA gene of which shares little homology with
      that from Haloferax volcanii. Introduction of an ISH28-based transposon (ThD28)
      into Haloarcula hispanica cells produced numerous transformants. Each of these
      was shown to contain an ISH-flanked mevinolin resistance determinant integrated
      into the cellular DNA. Integration was not obviously site specific. Transposon
      ThD26 (based on ISH26a), was less mobile, relative to ThD28, and the ISH2-based
      construct (ThD22) did not transpose at all in these cells. The further
      development of halobacterial transposons may provide useful genetic tools
      allowing rapid isolation and analysis of halobacterial genes, particularly those
      with no selectable phenotype.

PMID- 7804905
TI  - Cysteine protease activity of streptococcal pyrogenic exotoxin B.
AB  - Streptococcal pyrogenic exotoxin B (SPE B) was purified and its protease and
      mitogenic activities were investigated. The apparent molecular mass of SPE B
      purified in the presence of iodoacetic acid was 42 kDa, whereas 29-kDa SPE B was
      predominant without the reagent. A polyclonal antibody raised against the 29-kDa
      species reacted with both species, indicating that the 42-kDa species was a
      precursor of the 29-kDa entity. Both the 42- and 29-kDa species enhanced
      [3H]thymidine incorporation into human peripheral blood mononuclear cells,
      whereas neither had any effect on T cell depleted mononuclear cells. The 29-kDa
      SPE B possessed caseinolytic activity, with an optimal pH of 8, and the activity
      was specifically suppressed by the antibody. A group of cysteine protease
      inhibitors, but no serine-, metallo-, or acidic-protease inhibitors, limited the
      protease activity, whereas dithiothreitol increased the activity. The DNA
      sequence around a putative active cysteine residue was identical among the speB
      genes from Streptococcus pyogenes R70, NY-5, and T19. Taken together, these
      results indicate that SPE B is identical to a cysteine protease, streptopain (EC
      3.4.22.10).

PMID- 7804906
TI  - Characterization of the diversity of sulfate-reducing bacteria in soil and mining
      waste water environments by nucleic acid hybridization techniques.
AB  - Nucleic acid hybridization techniques were used to characterize the sulfate
      reducing bacterial communities at seven waste water and two soil sites in Canada.
      Genomic DNA was obtained from liquid enrichment cultures of samples taken from
      these nine sites. The liquid enrichment protocol favored growth of the sulfate
      reducing bacterial component of the communities at these sites. The genomic DNA
      preparations were analyzed with (i) a specific gene probe aimed at a single genus
      (Desulfovibrio), (ii) a general 16S rRNA gene probe aimed at all genera of
      sulfate-reducing bacteria and other bacteria, and (iii) whole genome probes aimed
      at specific bacteria. This three-pronged approach provided information on the
      sulfate-reducing bacterial community structures for the nine sites. These were
      compared with each other and with the sulfate-reducing bacterial communities of
      western Canadian oil field production waters, studied previously. It was found
      that there is considerable diversity in the sulfate-reducing bacterial community
      at each site. Most sulfate-reducing bacteria isolated from distinct sites are
      genomically different and differ also from sulfate-reducing bacteria found in oil
      field production waters.

PMID- 7804907
TI  - Detection of soluble methane monooxygenase producing Methylosinus trichosporium
      OB3b by polymerase chain reaction.
AB  - The soluble methane monooxygenase (sMMO) enzyme complex of methanotrophs
      cometabolizes haloaliphatic compounds such as trichloroethylene. Two 18-mer
      oligonucleotides as primary primers and a nested primer of the same length were
      selected to amplify specific DNA sequences of the sMMO gene cluster using
      polymerase chain reaction (PCR). Two DNA fragments of sizes 270 and 400 base
      pairs were obtained when purified DNA from the methanotroph Methylosinus
      trichosporium OB3b was used as template. The primers were specific for sMMO
      sequences of M. trichosporium, since none of the 13 bacterial isolates screened
      yielded the expected length of PCR-amplified DNA fragments. The detection limit
      of the PCR method was 5 x 10(2) cells of M. trichosporium. The sMMO sequences
      were successfully amplified in groundwater (containing native microbial
      population) when seeded with M. trichosporium, FP1 sense (5'-ATGTCCAGCGCTCATAAC
      3'), RP1 antisense (5'-TCAGATGTCGGTCAGGGC-3'), FP2 sense nested
      (5'GCCATCATCGGTCAGGGC-3'), and FP2 sense nested (5'-GCCATCATCGAGGACATC-3').

PMID- 7804908
TI  - Production and partial characterization of an endopolygalacturonase from
      Saccharomyces cerevisiae.
AB  - Saccharomyces cerevisiae CECT1389 secreted an extracellular endopolygalacturonase
      (EC 3.2.1.15) when grown in shake flasks in medium containing galactose alone, or
      either galactose and polygalacturonic acid or galactose and galacturonic acid as
      the carbon sources. The synthesis of the enzyme was repressed by glucose and by
      high oxygen tensions. The enzyme was partially purified by gel exclusion
      chromatography over Sephacryl S-200, where it showed an apparent molecular mass
      of 39 kDa; the value determined by high-performance liquid chromatography (HPLC)
      was 65 kDa. The optimal temperature and pH for enzyme activity were 45 degrees C
      and 5.5, respectively. The Km and Vmax values for polygalacturonic acid were 4.7
      mg.mL-1 and 6.4 nmol.mL-1.min-1. The Ki for HgCl2 was 6.8 x 10(-5) M. The enzyme
      exhibited an endo-splitting mechanism as deduced from viscosimetry experiments as
      well as from an HPLC study of the end products.

PMID- 7804909
TI  - Frequency of genes in aromatic and aliphatic hydrocarbon biodegradation pathways
      within bacterial populations from Alaskan sediments.
AB  - A significant proportion of the naturally occurring hydrocarbon-degrading
      populations within Alaskan sediments affected by the Exxon Valdez oil spill had
      both the xylE and alkB genes and could convert hexadecane and naphthalene to
      carbon dioxide; a greater proportion of the population had xylE than had alkB,
      reflecting the composition of the residual oil at the time of sampling; nearly
      equal populations with xylE alone, alkB alone, and xylE + alkB genes together
      were found after exposure to fresh crude oil; populations with xylE lacking alkB
      increased after enrichment on naphthalene. Thus, the genotypes of hydrocarbon
      degrading populations reflected the composition of the hydrocarbons to which they
      were exposed.

PMID- 7804910
TI  - Nurse practitioners and physicians: whose views does CMAJ represent?

PMID- 7804911
TI  - Fitness to drive: duties of physicians.

PMID- 7804912
TI  - A suspenseful moment in Canadian medicine.

PMID- 7804913
TI  - Effect of methotrexate on the fetus.

PMID- 7804914
TI  - Patient participation in decision making.

PMID- 7804915
TI  - Death in a restraint jacket.

PMID- 7804916
TI  - The medical hazards of television sports.

PMID- 7804917
TI  - Physicians and the pharmaceutical industry: under the influence?

PMID- 7804918
TI  - Injury prevention: the time has come.
AB  - Although cancer, heart disease and stroke occupy much of society's attention to
      health matters, injuries account for more potential years of life lost before age
      65 than all these diseases combined. The time has come to set the record straight
      and to give injury its rightful place on the health policy agenda. Contrary to
      popular belief, most injuries are no accident. More than 90% of injuries are both
      predictable and preventable. Injury prevention, a multidisciplinary effort, is
      coming of age in Canada. Education alone is not enough. New technology,
      innovative approaches to safety education and the mobilization of community
      resources can help to change behaviour and legislation to decrease the risk of
      injury. Physicians have an important role to play in this process.

PMID- 7804919
TI  - Basic statistics for clinicians: 1. Hypothesis testing.
AB  - In the first of a series of four articles the authors explain the statistical
      concepts of hypothesis testing and p values. In many clinical trials
      investigators test a null hypothesis that there is no difference between a new
      treatment and a placebo or between two treatments. The result of a single
      experiment will almost always show some difference between the experimental and
      the control groups. Is the difference due to chance, or is it large enough to
      reject the null hypothesis and conclude that there is a true difference in
      treatment effects? Statistical tests yield a p value: the probability that the
      experiment would show a difference as great or greater than that observed if the
      null hypothesis were true. By convention, p values of less than 0.05 are
      considered statistically significant, and investigators conclude that there is a
      real difference. However, the smaller the sample size, the greater the chance of
      erroneously concluding that the experimental treatment does not differ from the
      control--in statistical terms, the power of the test may be inadequate. Tests of
      several outcomes from one set of data may lead to an erroneous conclusion that an
      outcome is significant if the joint probability of the outcomes is not taken into
      account. Hypothesis testing has limitations, which will be discussed in the next
      article in the series.

PMID- 7804920
TI  - Radiographic abnormalities and the risk of lung cancer among workers exposed to
      silica dust in Ontario.
AB  - OBJECTIVE: To determine whether workers in Ontario who had been exposed to silica
      dust and who have radiographic abnormalities are at increased risk of lung
      cancer. DESIGN: Cohort and case-control studies of rates of death from lung
      cancer and cancer incidence rates; data were obtained from the Ontario Silicosis
      Surveillance Registry. Follow-up was through linkage to the Ontario mortality and
      cancer registries. SETTING: Ontario. PARTICIPANTS: A total of 523 workers with
      radiographic abnormalities and 1568 control subjects with normal radiographic
      findings who had been exposed to silica dust. Matching criteria were year of
      birth and the requirement that the control subject have a normal radiographic
      finding either later than or in the same year that the radiographic abnormality
      was identified in the silicosis subject. OUTCOME MEASURES: Standardized mortality
      ratios (SMRs), standardized incidence ratios (SIRs) and odds ratios for lung
      cancer. RESULTS: In the cohort analysis, with the Ontario population rates as
      reference, the all-cause SMR was 0.96 among the workers with radiographic
      abnormalities and 0.51 among the control subjects. The corresponding SIRs for
      lung cancer were 2.49 and 0.87 (p < 0.001). In the case-control analysis the
      workers with silicosis were more likely than the control subjects to have been
      smokers, but this difference likely accounted for only a small part of the
      difference in the incidence of lung cancer. The relative risk of lung cancer was
      elevated among the workers with silicosis from the foundry, mining and
      nonmetallic-minerals industries; however, the number of subjects was too small
      for a significant difference to be detected. Among the miners exposure to radon
      daughters did not affect the risk of lung cancer attributable to radiographic
      abnormalities. CONCLUSIONS: Radiographic abnormalities suggestive of exposure to
      silica dust are markers for increased risk of lung cancer. Physicians might thus
      wish to warn their patients with silica-associated radiographic abnormalities
      about the increased risk and to counsel those who smoke to stop.

PMID- 7804921
TI  - Bicyclist and environmental factors associated with fatal bicycle-related trauma
      in Ontario.
AB  - OBJECTIVE: To identify bicyclist and environmental factors associated with fatal
      bicycle-related trauma in Ontario. DESIGN: Retrospective study. SETTING: Ontario.
      PARTICIPANTS: Information was extracted from the provincial coroner's reports on
      212 people who had died of bicycle-related injuries in Ontario between 1986 and
      1991. OUTCOME MEASURES: Age, sex and helmet use of the bicyclist, time and place
      of the event, type of bicyclist or motorist error(s) and use of alcohol by
      bicyclist or motorist. RESULTS: Only 32% of the deaths involved bicyclists under
      15 years of age. The male-female ratio was 3.5. Over 75% of the cases involved
      head injury; however, only 8 (4%) of the bicyclists had been wearing a helmet. In
      91% of the cases death occurred as the result of a bicycle-motor vehicle
      collision. Most (65%) of the deaths for which the time was known occurred between
      4 pm and 8 am. Bicyclist error was the main cause of crash for 26 (79%) of the
      children less than 10 years old; it was also the main cause of crash among the
      bicyclists aged 10 to 19 years (43 [55%]) and those aged 45 years or more (15
      [44%]). However, motorist error was the most common cause of collision in the
      group of cyclists 20 to 44 years of age (42 [63%]). Alcohol was detected in the
      blood of 7% of the bicyclists killed; alcohol had been consumed by 30% of the
      motorists who claimed not to have seen the cyclist. CONCLUSIONS: Bicycle-related
      deaths result from factors that are generally avoidable. Identifiable risk
      factors other than lack of helmet use suggest that additional research is
      required to determine the benefits of preventive interventions aimed at reducing
      the number of such deaths. Age-specific strategies appear warranted.

PMID- 7804922
TI  - Society needs MD-assisted death, Canadian-trained medical director of US right-to
      die society says.
AB  - The growth of an American organization that supports the right to die is proof
      that the public wants and needs physician-assisted death, says a University of
      Alberta alumnus who is medical director of the Hemlock Society. Dr. Richard
      MacDonald says he believes individual patients have the right to decide whether
      they want to live with a certain quality of life. Both the American Medical
      Association and the CMA have spoken out against physician-assisted death, but
      MacDonald says this opposition is out of touch with the opinions of individual
      physicians and patients.

PMID- 7804924
TI  - Few Canadian hospitals qualify for "Baby Friendly" designation by promoting
      breast-feeding: survey.
AB  - Only five Canadian hospitals meet requirements for promoting breast-feeding as
      set out by the World Health Organization and qualify to receive the international
      "Baby Friendly" designation, a national survey has determined. Results from the
      survey of 523 hospitals were released at a Toronto conference.

PMID- 7804923
TI  - I am 60 and I have cancer.
AB  - In 1993, Ron Evason learned that he had prostate cancer. In this article,
      abbreviated from a speech he delivered last year, he describes his battle with
      the disease and the steps he has taken to overcome it. He also describes the
      lessons he has learned, including the need to ask probing questions of
      physicians.

PMID- 7804925
TI  - Oregon vote may mark watershed for right-to-die debate in Canada, US.
AB  - In November, Oregon became one of the first jurisdictions outside the Netherlands
      to allow physician-assisted suicide. Voters decided by a narrow 51% to 49% margin
      to pass a Death With Dignity Act, which allows terminally ill patients to receive
      a fatal prescription from a doctor after they meet several criteria. Observers
      note that the act's scope is narrow and that it would not have aided Sue
      Rodriguez, the British Columbia patient who went to court in an attempt to win
      the right to assisted suicide.

PMID- 7804926
TI  - Audience sceptical as critic challenges current system for paying Canada's MDs.
AB  - A recent CMA-sponsored conference on negotiations brought medical leaders from
      across Canada to Ottawa in September to hear experts discuss the current health
      care environment. Among the speakers was Dr. Michael Rachlis, a widely quoted
      critic of physicians' current role in the health care system. He said physicians
      and patients currently face major "equity issues," as some patients have a
      difficult time finding medical help because their serious illnesses are "worth"
      less to doctors, many of whom prefer to see patients with simple problems that
      can be dealt with in a few minutes. Several physicians reacted strongly to the
      criticism.

PMID- 7804927
TI  - Physician-led committee tackles youth-violence problem in one of Canada's fastest
      growing cities.
AB  - Dr. John O'Brien-Bell, a past president of the CMA, recently chaired the Advisory
      Committee on Youth Violence in Surrey, BC. It studied issues such as the
      incidence of violence, the evolution taking place in the city and society, and
      the erosion of traditional social values. In its final report, the committee
      recommended 78 possible steps for reducing violence among young Canadians.

PMID- 7804928
TI  - Public health and the Canadian state: the formative years, 1880 to 1920.

PMID- 7804929
TI  - Rural public health.

PMID- 7804930
TI  - A comparison of physical and laboratory measures between two Hutterite leute and
      the rural Saskatchewan population.
AB  - This study compares physical, laboratory and anthropometric measurements from
      each of two groups (leute) of Hutterites (N = 846) with a population of non
      Hutterites from rural Saskatchewan (N = 750). Marked interleute differences were
      observed in the comparative analysis with the non-Hutterite population.
      Dariusleut males had significantly greater mean diastolic and systolic blood
      pressures, total cholesterols, LDL cholesterols and Body Mass Indexes (BMI) than
      non-Hutterites. Compared with non-Hutterite women, the Dariusleut females had
      significantly greater mean diastolic and systolic blood pressure, HDL
      cholesterols, BMIs and waist-hip ratios. In contrast, the only significant
      difference between non-Hutterites and Lehrerleut males was in BMI. Lehrerleut
      females had significantly greater mean systolic blood pressures, HDL cholesterol
      levels and BMIs. While the surprising inter-leute differences may be due to
      subtle variations in lifestyle, the genetic isolation of the groups suggests
      heredity may offer a more likely explanation for the differences.

PMID- 7804931
TI  - Risk factors for non-use of seatbelts in rural and urban Alberta.

PMID- 7804932
TI  - Alternative medicine use in rural alberta.

PMID- 7804933
TI  - The high cost of a nutritionally adequate diet in four Yukon communities.
AB  - The cost of purchasing a nutritionally adequate diet in four Yukon communities
      was examined, based on the 46 food items and quantities of the federal
      government's Northern Food Basket. In Old Crow, unit purchase prices were on
      average 250% of those in Edmonton, while in three southern Yukon communities,
      unit purchase prices were about 125% of those in Edmonton. In quantities needed
      to meet weekly nutrient needs of a family of four, the cost in Old Crow was 320%
      of that in Edmonton, while in three southern Yukon communities, it was 140%. It
      appears that due to financial necessity, Yukon aboriginal people need continuing
      access to traditional food resources (wild game animals, birds, fish and
      berries). Since the Northern Food Basket does not include any traditional foods,
      it alone is of limited acceptability to these people. The high cost of marketed
      food and the role of traditional foods in contemporary diets should be considered
      in giving dietary advice and in determining food allowances in social assistance
      programs.

PMID- 7804934
TI  - Diet and drug consumption in a group of elderly residing in rural Newfoundland.
AB  - Dietary intakes and drug consumption were recorded for 24 seniors in a
      Newfoundland outport. Food frequency questionnaires suggested that the food
      groups consumed least adequately by the seniors were grain products and meat and
      alternatives: 71% did not consume the recommended daily minimum intake of grain
      products and 66.7% did not meet the minimum intake recommended for meat and
      alternatives. Inadequate consumption of milk products and vegetables and fruit
      was reported by 33.3% and 29.2% of the respondents respectively. All respondents
      used at least one medication on a regular basis. When the regular usage of both
      prescription and nonprescription drugs was considered, drug consumption ranged
      from one to eight. Antihypertensives and antianginals had the highest reported
      usage. This study suggests that many seniors simultaneously experience two
      factors with potentially negative effects on their nutritional status--high drug
      usage and poor dietary intake.

PMID- 7804935
TI  - Acute care hospital morbidity in the Blood Indian Band, 1984-87.
AB  - Acute care hospital morbidity of the Blood Indian Band was compared with that of
      all Albertans between April 1, 1984 and March 31, 1987. The Blood Indians had
      over 2.5 times as many hospital separations and 2.2 times as many patient days as
      the Albertans. The highest separation rare ratios by ICD-9-CM chapter for both
      Blood males and females were for endocrine, metabolic and nutritional disorders.
      Blood females had higher rate ratios for hospitalizations for all chapters except
      neoplasms and Blood males had higher rate ratios for all except congenital
      anomalies and neoplasms. For individual conditions, Blood males had the highest
      separation rate ratios for alcohol dependence syndrome, gastritis/duodenitis and
      diabetes mellitus. Bronchitis/emphysema and diabetes mellitus had the highest
      rate ratios for Blood females. The results are consistent with those reported in
      other studies of North American Indians. Their health status is more consistent
      with a developing country than that expected in Canada and does not appear to be
      improving.

PMID- 7804936
TI  - Classification of fatal occupational electrocutions.
AB  - The objective of this study was to describe fatal occupational electrocutions
      that occurred in Quebec between 1981 and 1988 and propose a classification
      suitable for setting up a prevention agenda. Of 63 fatalities, an investigation
      report was available in 57 (90.5%). They all occurred among males, 70.2% of whom
      were under the age of 35; 49.1% were performing a task related to the
      construction sector. A principal factor analysis allowed classification of 90.2%
      of the fatalities in two categories: victims assigned to electrical tasks indoors
      and those assigned to non-electrical tasks outdoors. The first group (56.5% of
      the cases) were electrocuted by direct contact with voltage less than 10 Kvolts
      and the second by the intermediary of a vector with voltage above 10 Kvolts. The
      identification of the two patterns of electrocutions provided an additional
      argument for shifting recommendations for prevention from educating the workers,
      to reducing the electrical hazards at the source.

PMID- 7804937
TI  - Occupational exposure to Mycobacterium bovis infection in deer and elk in
      Ontario.
AB  - In late 1991, two herds of deer and elk were depopulated at a slaughtering plant
      in Ontario, followed by processing of infected animals at a rendering plant. We
      conducted a questionnaire plus tuberculin skin-test survey of 104 exposed
      slaughtering and rendering plant workers, and government veterinarians and
      inspectors. Overall, 17 participants were skin-test positive, one of 51 initially
      skin-test negative subjects tested a second time three months later became
      positive, consistent with the risk associated with occupational exposure during
      the depopulation of tuberculous elk previously observed in Alberta. Deer farming
      is widespread, with 263 herds in Ontario. The likely route of transmission is
      through aerosols. Possible reasons for the low conversion rate include the use of
      respiratory protection, absence of a tanning plant, an enclosed rendering plant
      process, and late skin testing which may have underestimated the number of
      conversions. Recommendations for prevention are summarized; in particular,
      respiratory protection for work with infected herds should probably include high
      efficiency particulate face masks.

PMID- 7804938
TI  - [Study of a cancer aggregate in a metallurgy plant: practical implications for
      public health].
AB  - We present the strategy used to determine whether there was an excess of
      laryngeal cancer at a primary metal factory in Montreal. The study period
      extended from 1968 to 1987. Standardized mortality ratios (SMR) and standardized
      incidence ratios (SIR) were computed for different cancer sites. The number of
      person-years at risk was estimated (N = 10,860 person-years). This method
      permitted a summary evaluation of the situation. Statistically significant
      excesses were not observed for laryngeal cancer or any other site of cancer: SMRs
      and SIRs were elevated for certain cancers, particularly cancers of the larynx
      and cancers of the central nervous system (CNS). No association was observed with
      potential carcinogens in the workplace. However, all three CNS cancer cases were
      crane operators. Following this investigation, we recommended an industrial
      hygiene evaluation of the workplace.

PMID- 7804939
TI  - Consumer understanding and use of fat and cholesterol information on food labels.
AB  - As part of a comprehensive study looking at consumer awareness of nutrition
      labelling, this descriptive market research evaluated the understanding and use
      of label information about fat and cholesterol. Mall intercept interviews of 149
      food shoppers (80% women, 20% men) revealed that 60% believed it is extremely or
      very important to reduce their dietary fat. However, the claims "low in saturated
      fat" and "no cholesterol" and the term "non-hydrogenated" were often
      misunderstood. Fifty to 66% of respondents correctly interpreted "% B.F./M.F.",
      "low fat" versus "reduced in fat" claims, and the fat content of margarines. Only
      18% used % B.F. information to choose cheese and yoghurt. Depending on the claim,
      34-56% of respondents reported consulting other label information along with the
      claim; with the lowest rate of "additional consultation", (34%) reported for the
      "no cholesterol" claim. Consumer education is needed to enhance understanding and
      use of fat and cholesterol label information.

PMID- 7804940
TI  - Hepatitis B vaccination and screening for markers at a sexually transmitted
      disease clinic for men.
AB  - In Ontario, persons with multiple sexual partners became eligible for free
      hepatitis B vaccine in late 1991. From January 1992 to January 1993, a sexually
      transmitted disease (STD) clinic for men in Toronto was one site where the
      vaccine was delivered. The objectives of the study were to determine the
      seroprevalence of hepatitis B markers, the series completion rate for hepatitis B
      vaccine, and the seroprevalence of hepatitis B markers required before screening
      would be a cost-effective endeavour. The seroprevalence of anti-HBs in
      gay/bisexual men was 18.1% (95% CI: 15.3%-20.7%) and in heterosexual men was 5.1%
      (95% CI: 3.0-9.7%). HBsAg was detected in 0.9% (95% CI: 0.04%-1.8%) of
      gay/bisexual men and was undetected in heterosexual men. Completion of a full
      vaccine series was 47% for gay/bisexual men and 25% for heterosexual men (p =
      0.04). A combined seroprevalence of HBsAg and anti-HBs of at least 30-64%,
      depending on cost figures used, was required to justify screening prior to
      completion of a full series.

PMID- 7804941
TI  - [The opinions of Quebec physicians regarding AIDS: Part II].
AB  - Based on a representative sample of Quebec physicians (n = 879), this study
      assesses physicians' motivation to perform a clinical examination on an HIV
      infected patient and their opinion about issues related to HIV screening.
      Confronted with an HIV-infected patient, 70% of physicians would perform a
      clinical examination; however, more senior medical specialists with fewer
      contacts with patients seem less inclined to perform a clinical examination on
      these patients. Almost 80% agree with a mandatory nominal confidential
      notification of positive HIV screenees. However, 33% agree with the practice of
      contact tracing and 40% consider it acceptable to test a patient without his or
      her explicit consent. Even if Canada does not regulate the testing of immigrants
      for HIV, more than 75% of the respondents agree with such a policy. Finally, a
      negative association was observed between the intent to perform a clinical
      examination on an HIV-infected patient and a favourable attitude toward the
      screening of immigrants and the testing of patients without their consent.

PMID- 7804942
TI  - Regulated pre-employment medical examinations and their effect on the utilization
      of health services: the experience of 1,498 police cadets, Quebec, 1988.
AB  - Persons seeking employment in a police department must submit to a pre-induction
      medical screening after they have qualified on a compulsory test of physical
      stamina. The effect of this imposition on the utilization of health services was
      studied in a group of 1,498 police cadets whose use of medical and optometric
      services was monitored over a period of one year and compared with that of the
      general population of the same age and sex. Cadets have used about as much care
      as women of child-bearing age and were almost all exposed to physiological and
      radiological procedures that have no known utility in the medical surveillance of
      workers. It is estimated that the cost of providing the protection that is
      apparently sought by the regulation varies between $6,285 and $66,000 per person.

PMID- 7804944
TI  - Progress in hypertension control. Proceedings of the 9th Annual Scientific
      Meeting of the Canadian Coalition for High Blood Pressure Prevention and Control.
      Edmonton, Alberta, 12 June 1994.

PMID- 7804943
TI  - Patterns of calcium intake among French-Canadians living in Montreal.
AB  - In order to determine calcium intake, 1,450 French-Canadians of both sexes, all
      age groups and various socio-economic status, were recruited in Montreal and
      Laval using a stratified randomized selection. One thousand and sixty-five (73%)
      subjects completed food records: 82.4% for a period of seven days, the others for
      periods varying from one to six days, providing 6,590 days of food records.
      Subjects ranged in age from one month to 95 years with a mean age of 35.1 years.
      No seasonal variation in calcium intake was observed. On average, men consumed
      more calcium than women. This difference was significant for age groups 13 to 15,
      19 to 24 and 25 to 49 (p < 0.05). Womens' diets, however, had a higher calcium
      density than those of men, except among 10-15-year-olds. Mean calcium intake
      exceeded the RNI for the Canadian population in all age groups except females
      aged 10 to 15 years, and both men and women aged 50 years and over. The results
      of this study suggest that those in the study region most at risk for
      insufficient calcium intake are adolescent females and older men and women.

PMID- 7804945
TI  - Errors in assessment of blood pressure: patient factors.
AB  - This article reviews patient-related factors affecting blood pressure measurement
      and provides the scientific rationale underlying current recommendations for the
      measurement of blood pressure in the evaluation of hypertension. Information is
      included on the magnitude of errors that can occur when the recommendations are
      not followed. A variety of factors relating to the patient's emotions, activity,
      bodily function and environment cause blood pressure to fluctuate throughout the
      day such that peak systolic and diastolic blood pressures are often twice as high
      as trough levels. Many physicians fail to account for these factors when
      assessing a patient's blood pressure. Errors in the classification and treatment
      of a patient's blood pressure and the finding of labile blood pressure can occur
      often when patients are not adequately prepared in advance of the blood pressure
      measurement.

PMID- 7804946
TI  - Errors in assessment of blood pressure: blood pressure measuring technique.
AB  - This article reviews the recommended techniques for accurate and reproducible
      blood pressure measurements. The scientific basis underlying current
      recommendations for blood pressure measurement is presented. Many of the current
      recommendations are not followed in ambulatory care clinics and this paper will
      show how measurement errors in excess of 15 mm Hg or more can occur. Many
      patients will be misclassified and treated inappropriately when errors in blood
      pressure measurement of this magnitude are made. Rigorous adherence to proper
      blood pressure measurement is necessary to evaluate a patient's risk of
      cardiovascular disease, and to assess the need or efficacy of antihypertensive
      therapy.

PMID- 7804947
TI  - Errors in assessment of blood pressure: sphygmomanometers and blood pressure
      cuffs.
AB  - This article reviews the current recommendations on equipment when blood pressure
      is measured by sphygmomanometer. The scientific rationale underlying the current
      recommendations for selection and maintenance of blood pressure measuring
      equipment is presented. The errors that can occur when the recommendations are
      not followed are quantified whenever the data are available. Inadequate
      assessment and maintenance of equipment often lead to the use of faulty
      equipment, and as a result errors in the assessment of patients' blood pressure
      are likely to be common. If followed, the current guidelines for use and
      maintenance of equipment would remove most of the problems noted. Physicians must
      ensure that properly maintained and appropriate equipment is used to measure
      blood pressure.

PMID- 7804948
TI  - Guidelines for measurement of blood pressure, follow-up, and lifestyle
      counselling. Canadian Coalition for High Blood Pressure Prevention and Control.
AB  - As part of the Coalition's mandate to promote the prevention and control of high
      blood pressure in Canada, an interdisciplinary Workgroup was established to
      review and update the existing standards (1987) for blood pressure measurement
      and referral guidelines. The intent was to prepare a scientifically based
      document which contained practical guidelines for the measurement of blood
      pressure and criteria for follow-up, and one which promoted the concept of
      cardiovascular health in the assessment and interpretation of blood pressure
      readings. These guidelines were primarily developed to assist primary health care
      providers and/or clinicians to assess, monitor, counsel, refer, and develop
      treatment plans for adults-at-risk for high blood pressure or those with the
      confirmed diagnosis of hypertension. Readers are referred to The Canadian
      Hypertension Society Consensus Conference series (Canadian Medical Association
      Journal 1993) for specific guidelines on the evaluation, diagnosis, and treatment
      of hypertension. The document is divided into three sections: 1. Measurement of
      blood pressure 2. Criteria for follow-up 3. Guidelines for lifestyle counselling
      Each section cites the references used in developing the guidelines and where
      relevant, identifies other resources which can be used in clinical practice.

PMID- 7804949
TI  - Non-pharmacologic therapy in the management of hypertension: an update.
AB  - At the Canadian consensus conference on non-pharmacologic approaches to the
      management of high blood pressure in 1989 the evidence on the role of salt, body
      weight (obesity), alcohol, physical exercise, calcium and potassium
      supplementation, and stress management was reviewed, and recommendations were
      made. Most of the recommendations are still valid in 1994, although it is worth
      reviewing some of the data published since 1989. The evidence linking body weight
      or obesity to hypertension is strong, and weight reduction should be part of non
      pharmacologic therapy for hypertension. The data on physical exercise are
      stronger now, such that further recommendations may be worth considering. There
      are new data on the management of patients who have borderline blood pressure
      elevation or are predisposed to develop hypertension. The roles of weight loss,
      salt restriction and mineral replacement are reviewed. The management of mild
      hypertension can involve a choice between non-pharmacologic and pharmacologic
      therapy; however, a combination of both is usually necessary. Public education
      may have a growing role in the prevention of hypertension in selected population
      groups.

PMID- 7804950
TI  - Drug therapy for hypertension: where we are, and where we might be heading.
AB  - The past two decades have witnessed major improvements in antihypertensive drug
      therapy. Although diuretics and beta-adrenergic antagonists remain the drugs of
      choice, we now recommend much lower doses than we previously did. This appears to
      achieve equal blood pressure control while causing fewer side effects.
      Angiotensin-converting enzyme inhibitors and calcium antagonists are newer,
      relatively expensive drug classes whose benefits can be exploited in certain
      subgroups of patients. Whether they will lead to improved outcome in the
      uncomplicated hypertensive patient remains uncertain. New classes of drugs
      affecting the renin-angiotensin system are in various stages of development.
      Again, they have theoretical advantages over those currently available. Still
      other classes--thromboxane synthase or receptor antagonists and endothelin
      antagonists--appear promising in animal studies. Finally, in future, it may be
      possible to cure hypertension by altering a patient's genetic make-up.

PMID- 7804951
TI  - Reducing the incidence of coronary heart disease by managing hypertension:
      implications of syndrome X.
AB  - Syndrome X is a constellation of abnormalities; it appears to be strongly linked
      to insulin resistance and the risk of atherosclerosis. It consists of
      hypertension, glucose intolerance, obesity, dyslipidemia and, observed more
      recently, coagulation abnormalities. It is possible that treating blood pressure
      levels alone while ignoring or worsening other strongly associated risk factors
      has resulted in minimal effects on the incidence of coronary heart disease (CHD).
      Syndrome X has raised the awareness of these associated risk factors and has
      further led to the consideration of hypertension as a metabolic disease. The
      epidemiologic evidence in support of the link between insulin resistance and
      hypertension is reviewed, and the public health implications of these data are
      outlined.

PMID- 7804952
TI  - Cost-effectiveness issues in hypertension control.
AB  - In recent years, significant attention has been directed to the economics of
      health care. Pressures continue to mount to evaluate the cost-effectiveness of
      treating specific conditions and of utilizing specific treatment regimens. It has
      been demonstrated that the treatment of hypertension is very cost-effective. In
      fact, the total cost of hypertensive medication is more than offset by the
      savings from stroke alone. There is significant underidentification of
      hypertensive patients and therefore underprescribing of antihypertensive
      medications. Better identification would involve increased medication costs, but
      these should be more than offset by reduced hospital costs, improved productivity
      and enhanced quality of life. In selecting antihypertensive agents, particular
      attention should be given to the use of regimens that facilitate patient
      compliance. Once- or twice-a-day formulations, even when they are more expensive
      than formulations given three or four times daily, can result in lower overall
      treatment costs due to greater rates of compliance, better hypertension control
      and less use of physician, hospital and laboratory services.

PMID- 7804953
TI  - Risk factor awareness: a randomized telephone survey of public knowledge.
AB  - Health educators are often faced with the dilemma of developing materials or
      programs that begin at a level appropriate to the needs of individuals or the
      population as a whole. In 1992, a randomized telephone survey of the public's
      knowledge of risk factors relating to stroke was conducted in Saskatoon. The risk
      factors most frequently identified were poor diet (40%), hypertension (36%) and
      stress (36%). Respondents with a family history of stroke were significantly more
      likely to identify hypertension as a risk factor than those without such a
      history and significantly less likely to identify stress as a risk factor. In
      all, 24% reported a family history of acute myocardial infarction, and 28%
      reported a family history of stroke. Eighty percent were willing to learn more
      about the risk factors, and 88% were willing to make the appropriate lifestyle
      changes to reduce their risk of an event. Assessment of public knowledge can help
      in planning initiatives directed at prevention, early identification and
      appropriate referral.

PMID- 7804954
TI  - Hypertension control: historic perspectives--25 years of progress in Canada and
      around the world.
AB  - Hypertension has been estimated to affect over 15% of the general population in
      North America, and is a leading risk factor for coronary artery disease,
      congestive heart failure, stroke, kidney disease, and retinopathy. Since the
      early 70s there has been rapid development in the pharmacotherapy of hypertension
      and a concomitant effort to evaluate the efficacy of non-pharmacological
      interventions in controlling high blood pressure. At the same time it has become
      obvious that hypertension is not only a clinical but also a public health
      problem. Twenty five years ago only half of hypertensive patients were aware of
      their condition, and only 16% of the total number were under satisfactory
      control. In the past two decades the proportion of treated patients with well
      controlled hypertension increased to over 40%. Even today, however, one third are
      either unaware of their condition, or the reduction of blood pressure in those
      treated is unsatisfactory. A continuing effort is warranted to improve the
      management of hypertensive patients and to develop innovative public health
      measures in controlling this condition at a community level.

PMID- 7804955
TI  - High blood pressure in older persons: a high risk special population.
AB  - Blood pressure (BP), particularly systolic blood pressure (SBP), rises with
      advancing age. Isolated systolic hypertension is the most common type of
      hypertension (HTN) phenotype after age 70. Moreover, at similar BP levels the
      absolute risk for CVD is several fold higher in elderly than in young patients.
      End-organ damage is common, and significant renal impairment can be present even
      when serum creatinine levels are normal. All forms of HTN in the elderly should
      be treated. A recent meta-analysis of eight clinical trials involving elderly
      patients documented a 15/6 mm Hg treatment difference between intervention and
      control groups, and a lower rate of stroke, CHD and death from all causes in the
      intervention group. Gradual BP control into the "normal" range should be the goal
      in elderly patients. There is no convincing evidence that lowering BP is harmful
      (J-curve hypothesis). Coexisting medical conditions influence therapeutic
      choices. The suggested medical evaluation of elderly hypertensive patients with
      suspected secondary forms of HTN is covered as well as pervasive clinical myths
      about HTN in the elderly.

PMID- 7804956
TI  - Antitopoisomerase and anticentromere antibodies in the sclerodermatosus complex.

PMID- 7804957
TI  - Anti-DNA antibodies. Their idiotypes and SLE.

PMID- 7804959
TI  - Anti-endothelial cell antibodies and autoimmune diseases.

PMID- 7804958
TI  - Anti-Ro(SSA) and anti-La(SSB) antibodies in autoimmune rheumatic diseases.

PMID- 7804960
TI  - Antiphospholipid antibodies. A marker for thrombosis and recurrent abortion.

PMID- 7804961
TI  - Anti-neutrophil cytoplasmic autoantibodies (ANCA) and vasculitis.

PMID- 7804962
TI  - Menopausal estrogen replacement therapy in women with breast cancer.

PMID- 7804964
TI  - Acute basophilic leukemia in a child. Anaphylactoid reaction and coagulopathy
      secondary to vincristine-mediated degranulation.
AB  - BACKGROUND: Acute de novo basophilic leukemia (ABL) is uncommon in adults, and
      extremely rare in children. To the authors' knowledge, there have been no
      previous reports of anaphylactoid reactions from basophilic degranulation in
      children with this condition. METHODS: This report describes the
      clinicopathologic profile and complications of a patient with de novo ABL.
      RESULTS: Immediately after the first induction dose of intravenous vincristine,
      the patient developed an anaphylactoid reaction and disseminated intravascular
      coagulation with massive pulmonary hemorrhage. A normal serum tryptase level
      suggested that this life-threatening event was secondary to tumor lysis
      (basophilic degranulation), rather than to a mast-cell mediated anaphylactic
      reaction to vincristine. This interpretation is supported by the coagulation
      studies, which suggested release of heparin from the blast granules. CONCLUSIONS:
      Although de novo ABL is rare, it should be considered when cytoplasmic basophilic
      granules are seen in the leukemic cells of patients with what otherwise appears
      to be undifferentiated leukemia, and the pertinent diagnostic procedures should
      be undertaken. During the treatment of ABL, potential complications related to
      basophilic degranulation should be anticipated, and antihistamine prophylaxis may
      be of value.

PMID- 7804963
TI  - Age and sex are independent predictors of 5-fluorouracil toxicity. Analysis of a
      large scale phase III trial.
AB  - BACKGROUND: Cancer is most common in older age groups, but little information is
      available with regard to the impact of age on chemotherapy toxicity. This study
      was undertaken to determine if age is an independent risk factor for 5
      fluorouracil (5-FU) toxicity. METHODS: Toxicity data from a prospective,
      randomized, multiinstitution trial of 5-FU-based treatment for advanced
      colorectal cancer were analyzed. Toxicity for each organ system was graded.
      Individual organ toxicity proportions were compared using chi-square analysis. A
      logistic regression was performed using age (younger than 70 years vs. 70 years
      or older), sex, treatment arm, performance status, and length of therapy as model
      parameters to predict severe toxicity. Toxicity in 331 patients was analyzed.
      RESULTS: Advanced age was significantly associated with the occurrence of any
      severe toxicity (58 vs. 36%, P < 0.001), leukopenia (24 vs. 10%, P < 0.005),
      diarrhea (24 vs. 14%, P = 0.01), vomiting (15 vs. 5%, P = 0.01), severe toxicity
      in more than 2 organ systems (10 vs. 3%, P = 0.02), and treatment mortality (9
      vs. 2%, P = 0.01). By univariate analysis, age (P < 0.001) and sex (P < 0.0001)
      were independent predictors of severe toxicity. Twenty-two of 27 women age 70
      years or older had severe toxicity. CONCLUSIONS: Age 70 years or older and sex
      are risk factors for severe toxicity from 5-FU-based chemotherapy. Advanced age
      does not contraindicate the use of this type of chemotherapy, but close
      monitoring for multiple organ toxicities and vigorous supportive care of those
      with toxicity are required. Dosing decisions in older patients are difficult and
      must integrate assessments of organ function, comorbidities, overall physical
      status, and goals of treatment, in an effort to ensure the best possible outcome
      for these patients.

PMID- 7804965
TI  - Embryonal malignancies of unknown primary origin in children.
AB  - BACKGROUND: Little is known about embryonal malignancies of unknown primary
      origin in children. All such cases referred to a pediatric cancer center over a
      30-year period were reviewed to delineate their clinical and prognostic features
      and to develop recommendations for evaluation and therapy. METHODS: Seventeen
      patients with embryonal malignancies of unknown primary origin were identified by
      reviewing the institutional solid tumor database. The medical records, imaging
      studies, laboratory records, and pathology reports for each patient were reviewed
      and tabulated. RESULTS: Pathology review confirmed the original histologic
      diagnosis in 15 of the cases. Final diagnoses after review were rhabdomyosarcoma
      (n = 9), neuroblastoma (n = 7), and Ewing's sarcoma (n = 1). At initial
      evaluation, an extensive array of radiologic studies revealed multiple
      abnormalities in 16 cases. Bone marrow sampling and urinary catecholamine
      analysis were valuable diagnostic tools. A primary site of origin was identified
      in five patients: by interval assessments during treatment in two cases, and at
      autopsy in three. Although the median survival was only 6 months, 3 patients are
      alive at 12, 15 and 17 years after diagnosis. CONCLUSIONS: An exhaustive search
      for a primary lesion appears unwarranted in children with disseminated embryonal
      malignancies. Tumor sampling should be adequate for the pathologic work-up to
      determine the definitive diagnosis. Although the chances of cure are slight,
      tumor specific therapy may improve the interval of disease control, the quality
      of life, and the possibility of long term survival.

PMID- 7804966
TI  - Gastric carcinoids: an immunohistochemical and clinicopathologic study of 104
      patients.

PMID- 7804967
TI  - Comparative study of infectious complications of different types of chronic
      central venous access devices.

PMID- 7804968
TI  - A review of 76 patients with myelodysplastic syndromes treated with danazol.

PMID- 7804969
TI  - Acute promyelocytic leukemia with t(15;17) abnormality after chemotherapy
      containing etoposide for Langerhans cell histiocytosis.

PMID- 7804970
TI  - The National Cancer Data Base report on prostate cancer.

PMID- 7804971
TI  - Better survival in female patients with hepatocellular carcinoma. Possible causes
      from a pathologic approach.
AB  - BACKGROUND: Hepatocellular carcinoma is notably more prevalent in men than in
      women. METHODS: To examine the sex-related characteristics of patients with
      primary hepatocellular carcinoma, 35 women were compared with 243 men, both
      groups having undergone surgical resection of the tumor. RESULTS: Women had a
      lower incidence of tumor recurrence, with median disease free survival of 19.5
      months compared with 4.5 months for men (P < 0.001). Women also had more
      favorable actuarial survival than men [36.5 months for women compared with 12.4
      months for men (P = 0.002)]. Women had a significantly higher incidence (80%) of
      tumor encapsulation than men (45%) (P < 0.001). Furthermore, the tumors in women
      were frequently less invasive in terms of lower incidence of tumor
      microsatellites, liver invasion, and positive histologic margin. Tumor
      microsatellite formation was present with 16% of tumors in women, compared with
      60% for men (P < 0.0001). Liver invasion was found in 37% of tumors in women and
      61% in men (P = 0.03). Only 6% of tumors in women had a positive histologic
      margin, compared to 24% in men (P = 0.04). There was no statistical significance
      in the incidence of cirrhosis in the nontumorous liver, hepatitis B surface
      antigen positivity, mean age, or tumor size, between women and men. CONCLUSIONS:
      Women who had hepatocellular carcinoma and hepatic resection had better survival
      rates and a lower rate of tumor recurrence than male patients. The better
      prognosis in women with hepatocellular carcinoma appeared to be related to the
      pathobiologic characteristics of the tumor (i.e., frequent encapsulation and
      lower tumor invasiveness).

PMID- 7804972
TI  - Low dose octreotide and tamoxifen in the treatment of adenocarcinoma of the
      pancreas.
AB  - BACKGROUND: Data from experimental studies suggest that a combination of
      octreotide, the long acting somatostatin analogue, octreotide, and tamoxifen
      improves the survival of animals with pancreatic cancer. METHODS: Twelve patients
      with a tissue diagnosis of ductal adenocarcinoma of the pancreas were treated
      with 100 micrograms of octreotide three times per day and tamoxifen 10 mg twice
      daily. The survival of the octreotide-tamoxifen group was compared with a
      historic cohort of 68 untreated patients with pancreatic cancer, matched for age,
      sex, and TNM stage. RESULTS: The median survival times for the octreotide
      tamoxifen-treated group compared with the historic cohort were 12 and 3, months
      respectively. Actuarial one-year survival rates for the octreotide-tamoxifen
      treated group compared with the historic cohort were 59% and 16%, respectively.
      CONCLUSIONS: In this study, patients with unresectable and resected ductal
      adenocarcinoma of the pancreas had an apparently increased survival when treated
      with a combination of octreotide and tamoxifen. A randomized controlled trial to
      examine this potential therapeutic benefit is now indicated.

PMID- 7804973
TI  - Lung cancer in nonsmoking women. Histology and survival patterns.
AB  - BACKGROUND: Despite the widespread view that important clinical and etiologic
      differences exist between histologic categories of lung cancer, few studies have
      examined the accuracy of hospital-reported pathologic diagnoses of lung cancer.
      METHODS: A review of pathologic material and an assessment of survival patterns
      were conducted in conjunction with a recently completed case-control study of
      lung cancer among nonsmoking women in Missouri. Using established protocols,
      tissue slides from tumors of 482 patients were reviewed by 3 pathologists.
      RESULTS: Adenocarcinoma was the most common histologic type among former smokers
      and lifetime nonsmokers. The overall agreement rate between the original and
      review diagnoses was 65.6%. The positive predictive value ranged from 0.33 for
      bronchioalveolar carcinomas to 0.84 for adenocarcinomas. Agreement rates for
      small, medium, and large hospitals were 63.1, 66.6, and 66.2%, respectively.
      Survival rates were highest for bronchioalveolar carcinoma and lowest for small
      cell carcinoma. CONCLUSION: Given the importance of lung cancer to public health
      and the need to examine risk by histologic type, these data indicate that
      pathologic review of registry-reported lung cancer cases may be an important
      component of large scale studies of etiology.

PMID- 7804974
TI  - A phase III randomized, double-blind multiinstitutional trial of vaccinia
      melanoma oncolysate-active specific immunotherapy for patients with stage II
      melanoma.
AB  - BACKGROUND: In a Phase II trial, surgical adjuvant active specific immunotherapy
      using a live vaccinia virus-augmented allogeneic polyvalent melanoma cell lysate,
      vaccinia melanoma oncolysate (VMO), produced a significant disease free interval
      (DFI) in patients with International Union Against Cancer Stage II melanoma with
      positive lymph nodes. Therefore, a Phase III randomized prospective, double
      blind, multiinstitutional, surgical adjuvant VMO trial was performed to determine
      the efficacy of VMO to increase the DFI and the overall survival in this group of
      patients with Stage II disease. METHODS: Two hundred and fifty patients with
      Stage II melanoma were divided into two postsurgical groups. One group received
      VMO (total protein equals 2 mg/ml) and the other received the placebo of live
      vaccinia vaccine virus (V) (10(5.4) TCID50/ml), an adjuvant component of the VMO.
      Patients initially received these biologics once a week for 13 weeks and then
      once every 2 weeks for an additional 39 weeks or until recurrence. All surviving
      patients have been followed for at least 30 months. RESULTS: Statistical analysis
      of survival data (n = 217) for this first interim analysis shows that there is no
      statistically significant (P = 0.99) increase in DFI of patients treated with VMO
      (n = 104) when compared with V (n = 113). The median DFI is 38.0 months for
      patients treated with VMO and 37.0 months for patients treated with V. At 2- and
      4-year intervals, 70 and 38%, respectively, of patients treated with VMO vs. 66
      and 36%, respectively, of patients treated with V were free of melanoma. The
      median overall survival is not available because the patients treated with VMO
      have not yet reached the 50% mark and the median overall survival is 45.0 months
      for patients treated with V. At 2- and 4-year intervals, 70 and 38%,
      respectively, of VMO-treated patients survived when compared with 66 and 36%,
      respectively, of patients treated with V. Although the overall survival of
      patients treated with VMO is not statistically significant (P = 0.88) at this
      point, there is an increasing trend in the overall survival of patients treated
      with VMO; a 10% increase at the 4-year time point. Moreover, in the subset
      analysis, VMO-treated male patients (n = 63) showed a 17% improvement in survival
      at 4-year time point when compared with male patients treated with V (n = 67) (P
      = 0.19) at the same time point and male patients (n = 20) between the ages of 44
      and 57 having 1-5 positive lymph nodes showed a 37% difference in overall
      survival at the 4-year time point when compared with those patients treated with
      V (n = 18) (P = 0.13) at the same time point. CONCLUSION: In this first interim
      analysis, active specific immunotherapy with VMO vs. V showed no difference in
      the disease free interval or overall survival. Subset analyses likewise showed no
      significant differences in outcome but the data suggest a potential difference in
      immunoreactivity between male and female patients with melanoma that awaits
      further follow up and may merit further investigation.

PMID- 7804975
TI  - Carcinomatous lymphatic permeation. Prognostic significance in patients with
      rectal carcinoma--a long term prospective study.
AB  - BACKGROUND: The question of whether lymphatic permeation in rectal carcinoma is
      an index of prognosis remains controversial. METHODS: A long term prospective
      study of lymphatic permeation of 288 rectal carcinomas was performed. The degree
      of lymphatic permeation was divided into four stages (Ly0 through Ly3). The
      median follow-up for the surviving patients was 84 months (range, 23 to 151
      months). RESULTS: In patients with UICC Stage I or II disease, there was no
      correlation between the Ly0 and Ly1-3 groups' recurrence or survival rates. In
      patients with Stage IIIa disease, the rate of postoperative recurrence was
      significantly higher in the Ly1 or Ly2 + Ly3 groups compared with the Ly0 group.
      The 10-year survival and disease free survival rates in patients with Stage IIIa
      disease were both 90.0% in the Ly0 group, 63.6% and 62.5% in the Ly1 group, and
      52.0% and 45.5% in the Ly2 + Ly3 groups, respectively. A significant difference
      was noted in the survival rates between the Ly0 and Ly2 + Ly3 groups (P < 0.05),
      and was noted in the disease free survival rates between the Ly0 and Ly1 (or Ly2
      + Ly3) groups (P < 0.05, P < 0.005). In patients with Stage IIIb disease, there
      were trends toward higher recurrence, lower survival, or disease free survival
      rates in the Ly2 + Ly3 groups compared with the Ly1 group (P < 0.1). CONCLUSIONS:
      The degree of lymphatic permeation is an important prognostic factor in patients
      with Stage III disease, especially in those with Stage IIIa disease. It should be
      classified as a clinical subgroup.

PMID- 7804976
TI  - Estrogen replacement therapy withdrawal and regression of metastatic breast
      cancer.
AB  - BACKGROUND: Data regarding the effects of estrogen replacement therapy (ERT) and
      its withdrawal in patients with breast cancer are limited. METHODS: Four cases
      were observed involving estrogen replacement therapy withdrawal as management of
      metastatic breast cancer. RESULTS: Three patients with a history of primary
      breast cancer developed metastatic disease while on ERT. A fourth patient
      presented with metastatic breast cancer while on ERT. Withdrawal of this
      "physiologic" ERT alone as the only therapeutic intervention resulted in
      regression of metastatic disease in all four patients. CONCLUSIONS: In patients
      receiving ERT who develop metastatic breast cancer, withdrawal of ERT alone is a
      therapeutic option. Awareness of this phenomenon may be of value in management of
      these patients. The role of ERT and value of ERT withdrawal in patients with
      breast cancer deserve further study.

PMID- 7804977
TI  - U.S. farm women's participation in breast cancer screening practices.
AB  - BACKGROUND: Surveys of women in the general population indicate that women are
      being screened for breast cancer at a much lower rate than recommended. There has
      been a concern that women living in rural areas may be screened for breast cancer
      even less often than women in urban or suburban areas because of reduced access
      to health practitioners. METHODS: A random sample of farm women age 40 years or
      older from 4 rural counties in Michigan was surveyed on knowledge, attitudes, and
      use of breast cancer screening. RESULTS: Six hundred eighty farm women completed
      a questionnaire. This was a response rate of 63.8%. The percentages of farm women
      who reported ever having had a mammogram, having had a mammogram in the past 3
      years, and having had a mammogram in the last year were 80.6, 73.7, and 51.9%,
      respectively. The frequency of clinical breast examinations parallelled
      mammography usage at slightly higher percentages. Mammogram usage increased with
      higher education, income, and insurance coverage. Usage decreased in women age 75
      years or older (ever 63.1%, in the last 3 years 58.2%, and in the last year
      40.4%). Farm women were generally knowledgeable about symptoms and signs of
      breast cancer and understood the benefit of screening. There was, however, a
      range of answers on when to start or stop having a mammogram. Among farm women
      who reported not having a mammogram recently, the most important reasons were:
      haven't had any problems (29.4%), wasn't recommended by a doctor (14.3%), and
      procrastinated (11.3%). CONCLUSIONS: Farm women in this survey reported having
      had breast cancer screening at rates similar to or above those in the general
      population. Because of a limited response rate (63.5%) and the relative affluence
      of the farming community in the 4 counties surveyed, these results are probably
      not generalizable to all populations of farm or rural women.

PMID- 7804978
TI  - Partial mastectomy and breast reconstruction. A comparison of their effects on
      psychosocial adjustment, body image, and sexuality.
AB  - BACKGROUND: This retrospective study compared psychosocial adjustment, body
      image, and sexual function in women who had either breast conservation or
      reconstruction for early stage disease. METHODS: Questionnaires were completed at
      a mean of 4 years after surgery by 72 women who had partial mastectomy and 146
      women who had immediate breast reconstruction after mastectomy. RESULTS: In
      general, fewer than 20% of women reported poor adjustment on the domains
      measured. The two groups did not differ in overall psychosocial adjustment to
      illness, body image, or satisfaction with relationships or sexual life. There was
      a specific advantage of partial mastectomy over breast reconstruction in terms of
      maintaining pleasure and frequency of breast caressing during sexual activity.
      Women who had undergone chemotherapy had more sexual dysfunction, poorer body
      image, and more psychological distress. Hormonal therapy and radiation therapy,
      however, did not measurably affect quality of life. Factors predictive of greater
      psychosocial distress included a troubled marriage, a poor body image, sexual
      dissatisfaction, less education, and treatment with chemotherapy. CONCLUSIONS:
      The choice of local treatment had little psychosexual impact, whereas
      chemotherapy was associated with long term impairments.

PMID- 7804979
TI  - Relationship of the size of the invasive component of the primary breast
      carcinoma to axillary lymph node metastasis.
AB  - BACKGROUND: Invasive ductal carcinomas of the breast frequently have an
      intraductal (in situ) component at the tumor periphery that, in some cases, is
      included in the measurement of the tumor and thereby increases the size of the
      tumor beyond that of the invasive component. METHODS: Thirty-seven ductal
      carcinomas containing intraductal and invasive components were analyzed. The
      total tumor size, the size of the invasive component, the percentage of
      intraductal component, and the estimated tumor volume were assessed for each
      tumor. RESULTS: The mean size of the invasive component was 6.5 mm in axillary
      lymph node negative patients and 14.3 mm in those with axillary lymph node
      metastasis (P = 0.0001). The mean total tumor size was 13.7 mm and 17.6 mm (P =
      0.035) and the mean percent of intraductal component was 52% and 26% (P = 0.015)
      in patients with negative and positive axillary lymph nodes, respectively. Ninety
      two and four tenths percent of the difference in mean estimated total tumor
      volume between patients with negative and positive axillary lymph nodes was
      attributable to the difference in the volume of the invasive component alone.
      CONCLUSIONS: In small ductal carcinomas of the breast, the size of only the
      invasive component, as determined by microscopic measurement, is a better
      predictor of axillary lymph node status than is the total tumor size. The well
      established prognostic value of total tumor size largely is due to its reflection
      of the size of the invasive component.

PMID- 7804980
TI  - Malignant melanoma of the vulva. Evaluation of prognostic factors with emphasis
      on DNA ploidy in 75 patients.
AB  - BACKGROUND: To the authors' knowledge, the potential prognostic value of DNA
      ploidy in vulvar melanoma has not been evaluated in previous series. METHODS:
      Clinical data and follow-up information were retrieved from the hospital records
      of 75 patients treated from 1956 to 1987. Histopathologic specimens were reviewed
      for histologic type, depth of invasion, vessel invasion, and ulceration. Flow
      cytometric DNA measurements were performed on paraffin embedded samples. RESULTS:
      Forty-three patients had International Federation of Gynecology and Obstetrics
      Stage I disease, 14 Stage II, 8 Stage III and 10 Stage IV. Sixty-five patients
      were treated by surgery, six by radiotherapy, and four patients with advanced
      disease received no therapy. The surgical procedure was local excision in 17
      patients, vulvectomy in 22, and radical vulvectomy with inguinal lymph node
      dissection in 26. Five- and 10-year corrected survival rates were 46% and 37%,
      respectively. Recurrences were seen in 43 (66%) of the patients treated by
      surgery. Independent prognostic factors for corrected survival in the entire
      group of 75 patients were inguinal lymph node metastases (P = 0.016),
      angioinvasion (P = 0.027), tumor localization to clitoris, and multifocal tumors
      (P = 0.043). For the 65 patients treated by surgery, independent prognostic
      factors for disease free survival were angioinvasion (P < 0.001), age at
      diagnosis (P = 0.003), DNA ploidy (P = 0.004), and ulceration (P = 0.027). The
      independent prognostic factors for long term survival were tumor localization to
      clitoris (P = 0.018), DNA ploidy (P = 0.045), and inguinal lymph node involvement
      (P = 0.053). Radical surgery did not improve disease free or long term survival.
      CONCLUSIONS: DNA ploidy is an independent factor that predicts prognosis in
      patients with vulvar melanoma, and should be considered together with previously
      known factors. Radical surgery does not improve prognosis and is not recommended
      when the inguinal lymph nodes are clinically negative.

PMID- 7804981
TI  - The utility of the revised International Federation of Gynecology and Obstetrics
      histologic grading of endometrial adenocarcinoma using a defined nuclear grading
      system. A Gynecologic Oncology Group study.
AB  - BACKGROUND: The histologic grade of endometrial adenocarcinoma is related to the
      aggressiveness of the tumor and probability of death from disease. However, the
      ideal system for assignment of histologic grade remains controversial. In 1988,
      the International Federation of Gynecology and Obstetrics (FIGO) revised its
      recommendations for grading typical endometrial adenocarcinoma, such that grade
      is determined primarily by the architecture of the tumor and secondarily modified
      in the presence of "notable nuclear atypia"; this phrase, however, has never been
      defined, and therefore the prognostic validity of this system is unknown.
      METHODS: Seven hundred and fifteen women with clinical Stage I and occult Stage
      II endometrial adenocarcinomas (excluding serous or clear cell type) entered on a
      Gynecologic Oncology Group protocol, and those treated by total abdominal
      hysterectomy, bilateral salpingo-oophorectomy, and selective pelvic and para
      aortic lymph node sampling formed the study population. All cases were centrally
      reviewed and assigned an architectural grade and a nuclear grade using specific
      criteria. The FIGO grade was then determined. The various grading methods were
      examined based on ability to stratify patients into groups with differing rates
      of disease progression and relative survival at five years. RESULTS: The
      architectural grade, nuclear grade, and FIGO grade of tumors each were used to
      separate patients into groups with statistically significant different rates of
      progression of disease and relative survival. The FIGO modification of
      architectural grade resulted in the reassignment of 44 patients into a higher
      grade. The outcome for these 44 was worse than for the remaining patients in the
      initial grade but was similar to the group into which they were moved.
      CONCLUSIONS: If clearly specified criteria for architectural and nuclear grading
      are used and "notable nuclear atypia" is defined as grade 3 nuclei, the 1988 FIGO
      grading system has prognostic utility. The authors recommend this system as the
      standard method for the grading of typical endometrial adenocarcinoma.

PMID- 7804982
TI  - p53 expression and cell proliferation in squamous cell carcinomas of the head and
      neck.
AB  - BACKGROUND: In squamous cell carcinoma of the head and neck (SCCHN),
      overexpression of the p53 protein has been found in 34-80% of the tumors studied.
      No data are available regarding p53 expression versus tumor cell proliferation
      and prognosis for this tumor type. METHODS: p53 protein levels were studied by
      immunohistochemical staining of 33 primary SCCHN using 3 antibodies (DO7, PAb
      1801, and CM1) that react with different epitopes of the p53 protein. The
      cellular expression of p53 was compared with in vivo incorporation of the
      thymidine analog iododeoxyuridine (IdUrd) and expression of proliferating cell
      nuclear antigen (PCNA). RESULTS: Twenty-one tumors (64%) had a positive nuclear
      staining for p53 with the monoclonal antibody DO7, which reacts with a
      denaturation-resistant epitope in wild-type and mutant p53. PAb 1801 and CM1
      reacted with 19 and 20 tumors, respectively, all of which were DO7-positive. No
      correlation was found between incorporation of IdUrd and p53 expression or
      between PCNA and p53 expression. The data indicate that intracellular
      accumulation of the p53 protein was related to tumor stage and localization of
      the tumor. No indication of a clinical or prognostic significance of p53
      expression in SCCHN was found. CONCLUSIONS: No association between p53
      deregulation and tumor cell proliferation was found.

PMID- 7804983
TI  - Hodgkin's disease with spinal cord compression. A case report and a review of the
      literature.
AB  - BACKGROUND: Spinal cord compression is a rare complication of Hodgkin's disease,
      occurring in only 5% of cases, usually in the setting of progressive, advanced
      disease. As the initial symptom of Hodgkin's disease, it is extremely rare, with
      only a few cases reported in the literature. METHODS: A case report of a 46-year
      old man who presented with signs and symptoms of spinal cord compression and was
      found to have an extradural mass in the cervical and thoracic spine is described.
      Biopsy revealed Hodgkin's disease. This case report represents a unique case of a
      patient with Hodgkin's disease presenting with epidural disease, with spinal cord
      compression as the only apparent site of initial clinical involvement. A review
      of the literature of patients with Hodgkin's disease presenting with spinal cord
      compression from 1970 to the present is presented. RESULTS: The patient, whom we
      report, received chemotherapy followed by external beam radiation therapy and
      achieved complete resolution of symptoms and a complete response by radiologic
      criteria. Based on a review of the literature, Hodgkin's disease involving the
      spinal epidural space is very responsive to radiation therapy and chemotherapy
      with a good prognosis for both functional recovery (86%), complete response
      (61%), and long term survival. CONCLUSIONS: Chemotherapy and/or radiation therapy
      is successful treatment for Hodgkin's disease presenting with spinal cord
      compression. For the rare patient who presents with spinal cord compression as
      the initial symptom of Hodgkin's disease, the therapeutic options include
      chemotherapy alone, radiation therapy alone, or combined modality therapy.

PMID- 7804985
TI  - American Cancer Society National Conference on Skin Cancers. Phoenix, Arizona,
      April 14-16, 1994. Proceedings.

PMID- 7804984
TI  - Major histocompatibility proteins, anti-Hu antibodies, and paraneoplastic
      encephalomyelitis in neuroblastoma and small cell lung cancer.
AB  - BACKGROUND: Patients with neuroendocrine-related tumors and paraneoplastic
      encephalomyelitis (PEM) or paraneoplastic sensory neuronopathy (PSN) develop high
      titers of antibodies, called anti-Hu, against neuronal proteins expressed in
      their tumors, usually small cell lung cancer (SCLC). These tumors appear to be
      more indolent than those not associated with anti-Hu antibodies. The aims of this
      study were to determine 1) if patients with neuroblastoma (NB) also have anti-Hu
      antibodies, 2) the correlation between antibody titer and survival, and 3) if
      coexpression of Hu antigens and major histocompatibility proteins (MHC) by the
      tumor correlates with the development of anti-Hu associated PEM/PSN: METHODS:
      Using immunohistochemistry and Western blot analysis, the sera of 109 patients
      with NB whose neurologic condition was concealed at the time of the study were
      examined for the presence of anti-Hu antibodies. The expression of Hu antigens
      and MHC proteins in 50 nonselected NB and 26 SCLC (16 known to be from
      seropositive and 10 from seronegative patients) was examined using
      immunohistochemistry. RESULTS: Four Stage 4 NB patients were seropositive and had
      longer survival (median 86 months) than 71 seronegative patients in the same age
      group and with the same tumor stage (median survival, 28.5 months). Seventy-eight
      percent of NB and all SCLC expressed Hu antigens. Overall, 17 of 20 tumors from
      seropositive patients expressed both Hu and MHC Class I proteins, but only 4 of
      30 tumors from seronegative patients expressed both proteins (P < 0.0001).
      CONCLUSIONS: 1) Some patients with NB develop anti-Hu antibodies; a search for
      that type of tumor is indicated in seropositive children, 2) most NBs and SCLCs
      express Hu antigens but only a few are associated with anti-Hu antibodies, and 3)
      Class I MHC expressed by some Hu antigen-bearing tumors may play a role in the
      development of anti-Hu associated PEM/PSN:

PMID- 7804986
TI  - An overview of skin cancers. Incidence and causation.
AB  - The incidence and mortality rates of skin cancer are rising in the United States
      and in many other countries. Concerns about stratospheric ozone depletion adding
      to the problem have made many organizations look at public and professional
      health programs as a possible solution. Early detection can reduce the problem in
      the short term, because mortality due to melanoma is clearly related to the depth
      of invasion of the tumor when it is removed. This is the factor which is amenable
      to change in an education program on early detection. Exposure to sunlight is
      clearly related to risk of development of skin cancer, including both melanoma
      and nonmelanoma skin cancers. This is the component of the equation of
      constitutional predisposition plus exposure to environmental risk factors leading
      to skin cancer that is amenable to change as a result of educational programs. On
      the basis of available data, there is a case for further development, provision,
      and evaluation of public and professional education programs designed to control
      what is becoming a major public health problem in the community.

PMID- 7804987
TI  - Public education and cancer of the skin. What do people need to know about
      melanoma and nonmelanoma skin cancer?
AB  - Cutaneous melanoma (CM) and nonmelanoma skin cancer (NMSC) have a high chance for
      cure if detected in an early phase of development. Patients who have these tumors
      may now be treated in the outpatient setting with a minimum of discomfort,
      inconvenience, and cost. Most skin cancer deaths are caused by CM. Until
      recently, CM incidence in the United States has been increasing faster than any
      other potentially lethal cancer, attributable at least in part to aggressive case
      detection and greater public awareness about the significance of risk factors and
      early warning signs of evolving tumors, resulting in increased numbers of curable
      tumors. Most CMs are discovered by patients or close acquaintances. Most CM
      deaths are related to patient delay in seeking medical care. Patient delay is
      attributed mostly to lack of knowledge rather than to fear and denial. In the
      United States, primary prevention of CM and NMSC has focused on encouraging
      sensible sun-exposure behaviors, while secondary prevention consists of a yearly
      national campaign that promotes skin awareness and self-examination and free
      examinations to detect evolving tumors, sponsored by the American Academy of
      Dermatology and the American Cancer Society. More attention is needed to
      encourage timely consultation for evolving tumors and predisposing risk factors
      and to focus screening and surveillance efforts of those people at greatest risk.
      Public education must continue to promote personal responsibility in the
      intervention process to reduce the morbidity and mortality associated with CM and
      NMSC.

PMID- 7804988
TI  - Occupation and the risk of malignant melanoma.
AB  - BACKGROUND: The incidence of malignant melanoma is increasing rapidly. The risk
      for development of malignant melanoma has been reported to be higher in persons
      of higher socioeconomic status. METHODS: This case-control study explores the
      relation between occupation and malignant melanoma relative risk through analysis
      of data collected by the American Cancer Society. A total of 1.2 million people
      were enrolled in a study of lifestyles and environmental factors in relation to
      mortality from cancer and other diseases. A total of 2780 persons had a history
      of malignant melanoma when the study began or developed malignant melanoma during
      the 6-year study follow-up period. The controls were matched for age, sex, race,
      and geographic location on an approximately 1:3 basis to persons selected from
      the remaining people enrolled. RESULTS: In men, malignant melanoma risk was
      significantly higher in high-paying versus low-paying occupations (odds ratio
      [OR], = 1.58; P < 0.001) and in white-collar versus blue-collar occupations (OR =
      1.33; P < 0.001). No significant conclusions could be drawn for women. No
      significant difference in risk was noted between those with indoor versus outdoor
      occupations. Among specific occupational exposures, only exposure to X-rays
      significantly raised malignant melanoma risk (OR = 1.37; P = 0.002). CONCLUSION:
      Upper pay scale and white-collar occupations significantly increase the risk for
      development of malignant melanoma.

PMID- 7804989
TI  - Precursors to skin cancer.
AB  - Certain cutaneous lesions serve as both precursors of skin cancer and markers for
      increased risk. The solar or actinic keratosis serves such a role for the
      nonmelanoma (NMSC) forms of skin cancer (basal cell carcinoma and squamous cell
      carcinoma). Clinically, these keratoses manifest as rough, scaly, erythematous
      patches on chronically sun-exposed surfaces. Conversion to squamous cell
      carcinoma in an individual lesion is uncommon and has been estimated at 1 per
      1000 per year. Individuals with actinic keratoses have had sufficient chronic
      photodamage to produce skin cancer, and regular surveillance is recommended. The
      second precursor for invasive NMSC is Bowen's disease (squamous cell carcinoma in
      situ). Invasion of the dermis results in frank squamous cell carcinoma. Some
      types of viral warts may develop into squamous cell carcinoma. The most important
      precursor/marker for melanoma is the clinically atypical mole (CAM) or dysplastic
      nevus. CAMs occur in 5-10% of the U.S. population. CAMs, under photographic
      follow-up, have been observed to evolve into cutaneous melanoma. The frequency of
      conversion to melanoma of any single CAM is quite low; however, in melanoma-prone
      families, prospectively diagnosed melanomas arise in association with a
      histopathologically observed dysplastic nevus in more than 80% of the cases.
      Giant congenital melanocytic nevi have an approximately 6% lifetime risk of
      melanoma development. The risk associated with small congenital nevi is
      uncertain. Lentigo maligna develop into invasive melanoma with a frequency
      reported in the literature ranging from 5-50%.

PMID- 7804990
TI  - Public education projects in skin cancer. The evolution of skin cancer prevention
      education for children at a comprehensive cancer center.
AB  - BACKGROUND: Skin cancer affects more Americans than any other type of cancer.
      Children are prime targets for prevention education, because sun overexposure in
      early childhood may affect the development of skin cancer later in life.
      Preventive behaviors adopted early in life may be less resistant to change than
      those acquired in adulthood. Thus, there is a need to educate children at an
      early age about sun overexposure. METHODS: This article describes the evolution
      of skin cancer prevention research at the Arizona Cancer Center, a National
      Cancer Institute--designated comprehensive cancer center. Research focusing on
      children is high-lighted. RESULTS: From its roots in the Arizona Sun Awareness
      Project, an informal public skin cancer education program, skin cancer prevention
      research at the Arizona Cancer Center has produced two developmentally
      appropriate, age-based curricula aimed at teaching children about the benefits
      and dangers of the sun. The elementary school curriculum, Sunny Days, Healthy
      Ways, has undergone two tests of feasibility and is the intervention used in a
      large, randomized, experimental trial. The preschool curriculum, Be Sun Safe, has
      been tested in a randomized trial and was found to have a positive effect on
      preschoolers' knowledge and comprehension of sun safety. CONCLUSIONS: Educating
      children about skin cancer may be an important way of decreasing the incidence of
      skin cancer. Although informal skin cancer prevention education can be helpful,
      educational programs preferably should be research based and evaluated for
      effectiveness before public distribution. The Arizona Cancer Center experience
      can serve as a model for other programs.

PMID- 7804991
TI  - The Under Cover Skin Cancer Prevention Project. A community-based program in four
      Texas cities.
AB  - BACKGROUND: Although behavioral research has contributed much to our
      understanding of tobacco use and the development and evaluation of theory-based
      prevention strategies, the increasing incidence of nonmelanoma skin cancer
      continues to receive far less, but deserving, attention. METHODS: The Under Cover
      Skin Cancer Prevention Project represents a unique community awareness and
      education program that utilizes media partners in four Texas cities to
      disseminate ultraviolet (UV) radiation readings four times daily, along with
      education and behavioral change messages. Designed to change knowledge and
      attitudes about ultraviolet radiation exposure while promoting risk-reduction
      strategies, the program includes UV solar meters linked via telephone modem to
      provide continuous monitoring of UV exposure. RESULTS: Telephone survey results
      conducted during the summers of 1992 and 1993 (n = 1200 and 400, respectively)
      are part of a trend analysis study designed to access knowledge, attitude, and
      belief variables. Findings reveal that the general public, while knowledgeable of
      the sun's dangers, are less likely to practice prevention because of peer
      pressure and social norms favoring a tanned, "healthy" look. Trend data indicates
      that the media partner concept is an effective means for creating community
      awareness. CONCLUSIONS: Community-based programs utilizing media partners along
      with interventions that address issues of social norms and peer pressure appear
      to be effective strategies for increasing skin cancer prevention strategies among
      the general population. Long term, theory-based intervention strategies designed
      to test this media-based approach with a case-control, longitudinal design are
      needed.

PMID- 7804992
TI  - Public education projects in skin cancer. Experience of the Canadian Dermatology
      Association.
AB  - The mandate of the Canadian Dermatology Association's Sun Awareness Program is to
      increase awareness of the dangers of the sun's ultraviolet (UV) rays and to
      provide information on prevention and early detection of skin cancer. Major
      projects include an annual national press campaign, which reaches an increasing
      number of Canadians each year, and the production and distribution of educational
      materials. Each year during Sun Awareness Week, screening stations have been
      established across the country, staffed by volunteer dermatologists and members
      of the Canadian Cancer Society. In Vancouver between 1991 and 1993, 1767 people
      were screened for skin cancer. Results indicate that these events can attract
      people at risk for skin cancer, even though people older than age 65 are probably
      underrepresented as a group. Although popular with the public, these screenings
      are difficult to organize and are limited by human resources. These events
      continue in limited numbers, because they provide an excellent venue for the
      dissemination of educational material. Cooperation with federal agencies has been
      a major focus of the program. For the past 2 years, educational material on
      protecting newborns and children from the sun has been made available free to
      every new mother in Canada, while Environment Canada's Ultraviolet index program
      provides daily information on UV intensity along with public health messages.
      With the realization that health promotion requires a sustained change in
      behavior of an individual, we are now embarking on a national program to evaluate
      the knowledge, attitudes, and behavior of Canadians concerning UV radiation. With
      this information, we hope to adapt our educational materials so that people will
      adopt and maintain healthy behavior choices while out in the sun.

PMID- 7804994
TI  - The early detection of and screening for melanoma. International status.
AB  - Cutaneous melanoma is an increasingly common public health problem in
      industrialized nations. In theory, education and early detection should decrease
      melanoma morbidity and mortality, because the lesion is external and visible,
      risk factors are known, and thin tumors are associated with a high 5-year
      survival rate. The efficacy of early detection and screening programs, however,
      remains untested by randomized trials. Some early data are available from
      melanoma prevention and control efforts that have begun in many nations over the
      past decade. Textbook definitions of cancer screening are particularly
      challenging when applied to skin cancer control. Although some propose that there
      are rigid differences among screening, education, and early detection of skin
      cancer, the visible nature of this cancer makes early detection through education
      and screening inextricably intertwined. This article discusses the intermediate
      measures of education and screening within the context of the American Academy of
      Dermatology programs. Over the next few decades, screening and education for
      melanoma and other skin cancer will receive increasing worldwide attention.
      Multiple strategies will be required to combat increasing incidence and mortality
      rates. Screening and educational programs have been implemented worldwide, but
      data on their effects are only just being collected. Future collaborative work in
      melanoma/skin cancer prevention, education, and early detection holds promise as
      a way to decrease mortality and save lives.

PMID- 7804993
TI  - Skin cancer in African Americans.
AB  - Skin cancer is the most common type of malignancy in the United States. Incidence
      within the African American population remains relatively low, but data is
      limited for this racial group, making accurate determination of incidence and
      mortality difficult. Factors implicated as causative in the pathogenesis of
      cutaneous malignancy in African Americans include, but are by no means limited
      to, sunlight, albinism, burn scars, X-rays, preexisting pigmented lesions,
      chronic inflammation, and chronic discoid lupus erythematosus. Anatomic
      distribution of lesions may be similar to that seen in whites for basal cell
      carcinoma but not for other skin cancers. For squamous cell carcinoma, melanoma,
      and cutaneous T-cell lymphoma, African Americans do not as well in terms of
      mortality as do whites. This difference probably is due either to the fact that
      African Americans have more advanced stages of disease at diagnosis than do
      whites or, in some cases, because the course of the disease is more aggressive in
      African Americans for reasons yet unknown. There is a need for heightened
      awareness of skin cancer in African Americans by patients and physicians.
      Emphasis should be on education and early diagnosis with the primary goal in mind
      being the reduction of incidence of and mortality due to skin cancer in African
      Americans. In addition, because of environmental factors, African Americans will
      be exposed to more solar ultraviolet radiation in the future. Strategies should
      be developed for public education to keep this exposure to low levels in this
      racial group.

PMID- 7804995
TI  - Techniques of cutaneous examination for the detection of skin cancer.
AB  - Skin cancers are the most common cancers in humans. The American Cancer Society
      estimates that in the United States more than 700,000 new skin cancers are
      diagnosed annually. Although the majority of nonmelanoma skin cancers occur on
      visibly exposed anatomic areas, most malignant melanomas occur on body sites
      obscured by clothing. The high mortality associated with advanced melanomas
      emphasizes the importance of performing regular total cutaneous examinations in
      all patients to detect early, easily curable lesions. A number of techniques aid
      in these examinations: (1) physical and psychologic preparation of the patient;
      (2) appropriate lighting and a suitable examination table; (3) when indicated,
      use of Wood's light, dermoscopy, and photography. In addition, any suspicious
      lesion should be biopsied promptly either in parte or in toto. Lastly, the
      patient should be educated about the signs and symptoms of skin cancer, the role
      of sunlight in causing skin cancer, and the need for sun avoidance and/or
      protection. By heightening public awareness of the high incidence of cancers of
      the skin and by emphasizing the need for routine examination of the entire
      cutaneous surface, most cutaneous malignancies can be diagnosed early when they
      can be cured by simple surgical procedures.

PMID- 7804996
TI  - Barriers to effective skin cancer detection.
AB  - BACKGROUND: In response to the dramatic rise in melanoma incidence, numerous
      health care specialists have encouraged primary care providers to increase skin
      cancer detection efforts. Although primary care providers currently find more
      melanomas than do dermatologists, many detection opportunities are missed. In
      addition, primary care providers occasionally incorrectly reassure patients about
      specific lesions. Nevertheless, there is little evidence that efforts to detect
      skin cancer are growing. This paper discusses barriers to skin cancer detection
      and potential ways to increase screening. METHODS: Methods involve the review of
      the medical literature and the author's synthesis of this information. RESULTS:
      The principle barriers to skin cancer detection are that it is a low priority in
      primary care, that the majority of exams do not result in significant findings,
      and that many providers lack expertise to adequately identify high risk lesions.
      Lack of reimbursement for preventive care, inadequate time for complete skin
      exams, and distraction by other health problems also play a role in limiting skin
      cancer detection efforts. CONCLUSIONS: Relying on primary care-based skin cancer
      detection as the only means to increase skin cancer identification is an unwise
      policy. Approaches that may be able to increase skin cancer prevention and
      detection include increased (1) collaboration between skin cancer specialists and
      experts in primary care, (2) focus on providers of pediatric care, (3) advocacy
      for reimbursement of preventive health care, (4) educational efforts for the
      public to request skin exams, and (5) education directed to providers in high
      risk areas.

PMID- 7804998
TI  - Melanoma skin cancer screenings. A how-to approach.
AB  - Development of a workshop on skin cancer screening should begin with physicians
      who are able to best diagnose and treat skin cancer, that is, dermatologists who
      are board certified or board eligible. Local societies should then be involved as
      well as organizations that can offer ancillary help such as screening, clinics'
      location and assisting with personnel financial aid, and exposure to the public,
      such as advertising. Support groups then become essential to a good screening.
      The help of the American Cancer Society, local churches, clubs, and others is
      beneficial. The organization should have a central organizing body that sets the
      dates and locations for the clinics and that helps get supplies, such as tables,
      screens for privacy, and literature. Volunteers can help with sign-in and sign
      out sheets for the screening and can act as traffic directors and assist the
      physicians. Media exposure then becomes important. A TV or radio show can get the
      public's attention, for example, by releasing the latest data on skin cancer or
      by presenting a solar meter project showing the local risk of ultraviolet
      radiation. The workshop itself should begin on time. Additionally, a cutoff time
      is also needed. In the final stage, the forms should be processed and a follow-up
      evaluation should be done on the number of patients seen, precancerous and
      cancerous lesions found, and the potential for future functions. Popular
      ancillary aids are good literature on the subjects discussed, and samples of
      sunscreens (SPF 15 or better) that are donated by pharmaceutical companies.

PMID- 7804997
TI  - Principles of management of basal and squamous cell carcinoma of the skin.
AB  - There are a number of options available to the physician for the primary
      management of basal cell and squamous cell carcinoma of the skin. The most
      commonly used treatment modalities are primary resection, radiation therapy, and
      Mohs' micrographic surgery. Although each of these modalities can be used to
      treat most skin cancers in a variety of settings, each of these forms of cancer
      treatment is more appropriate in some settings and less appropriate in others.
      The role of each mode of therapy is discussed, based on effectiveness for cure,
      short and long term side effects, and cost of treatment. The appropriate role of
      the physician treating skin carcinoma is to choose the most effective treatment
      based on the above criteria and not to make the tumor fit any particular
      treatment modality.

PMID- 7804999
TI  - Basal cell and squamous cell carcinomas are important risk factors for cutaneous
      malignant melanoma. Screening implications.
AB  - BACKGROUND: This study was designed to determine the risk of developing malignant
      melanoma (MM) in patients with a history of basal cell and/or squamous cell skin
      cancer (BCC/SCC) and to determine whether surveillance efforts can be directed
      toward these patients for the detection of early MMs. METHODS: The study cohort
      was followed by annual total cutaneous examination (TCE). Controls consisted of
      individuals from the United States population matched for age, sex, and length of
      follow-up. The anatomic locations of the study cohorts' newly diagnosed MMs were
      plotted on an anatomic chart. The setting was a private dermatology practice. Two
      hundred, ninety consecutive white patients with a history of BCC/SCC but with no
      personal or family history of MM were followed by annual TCEs. The main outcome
      measures were the relative risk of developing MM and their prognosis. RESULTS:
      Ten of the 290 patients developed an MM within an average of 109 months of follow
      up (range, 3-17 years). All MMs were less than 0.70 mm in Breslow thickness and
      80% occurred on usually clothed cutaneous sites. The expected number of MMs in
      the control population was 0.59 (P = 0.006), resulting in a relative risk of 17.
      CONCLUSION: Patients with BCC/SCC skin cancer are at substantial increased risk
      for developing MM. Regular and life-long surveillance TCE is an inexpensive and
      effective method for detecting curable MMs in such patients.

PMID- 7805000
TI  - Malignant melanoma. Primary surgical management (excision and node dissection)
      based on pathology and staging.
AB  - The diagnosis of malignant melanoma is based on clinical grounds and a properly
      performed biopsy, preferably excision, so that the type of melanoma and the
      thickness can be assessed by methods described by Clark and Breslow. These
      facilitate clinical and pathologic staging. Excisions with conservative margins
      for thin lesions (less than 1.0 mm in thickness) and more extensive margins for
      thicker lesions are appropriate. The issue of elective lymph node dissection is
      controversial. Most authors agree it is not indicated for lesions less than 1.0
      mm thick and may offer little advantage for lesions greater than 4.0 mm thick.
      Several retrospective studies show a survival advantage in patients with
      "intermediate" thickness melanomas who may have occult nodal metastases. However,
      there are prospective randomized clinical trials supporting the concept that
      positive lymph nodes are a manifestations of systemic disease, and survival is
      equivalent in patients who have subsequent therapeutic lymph node dissections. A
      procedure using intraoperative lymphatic mapping and selective lymphadenectomy
      may identify those patients who are likely to benefit from lymphadenectomy.

PMID- 7805001
TI  - The role of adjuvant therapy in melanoma management.
AB  - Adequate wide excision of a primary cutaneous melanoma is associated with a 10
      year cure rate of 85% when the tumor's depth is less than 1.5 mm (American Joint
      Committee on Cancer [AJCC] Stage I). However, 50% of patients with deep (> 4 mm)
      primary melanomas, 60-85% of those with regional lymph node metastases (AJCC
      Stage III), and 95% of those with metastases to distant sites (AJCC Stage IV)
      will experience recurrence, which is associated with a dismal prognosis. Adjuvant
      therapy of melanoma assumes that treatment will be more effective when the tumor
      burden is small. In the 1970s and 1980s, randomized trials tested the efficacy of
      chemotherapy, nonspecific immunotherapy, levamisole, and regional perfusion
      therapy in patients with AJCC Stage II and III melanoma. Dacarbazine (DTIC) alone
      or in combination with other chemotherapeutic drugs or with nonspecific
      immunotherapy did not significantly improve disease free or overall survival. Of
      the four levamisole trials, only the study conducted by the National Cancer
      Institute of Canada revealed a reduction in recurrence and mortality; however,
      this reduction was not significant by multivariate analysis. The value of
      regional perfusion therapy following resection of high risk extremity melanomas
      is currently being determined by multiinstitutional studies conducted by the
      World Health Organization and the North American Perfusion Group. Multi
      institutional trials also are examining the adjuvant role of interferon-alpha in
      patients with deep (> 3 mm) primary melanomas or positive regional lymph nodes;
      results should reveal its optimum dose and duration of treatment (3 x 10(6) U for
      > or = 2 years versus 10 x 10(6) U/m2 for 1 year, subcutaneously 3 times a week)
      and its impact on survival. A randomized trial of interferon-gamma undertaken by
      the Southwest Oncology Group was discontinued after interim analysis indicated an
      adverse effect. Phase II trials indicate that active specific immunotherapy can
      alter the natural course of AJCC Stage III and IV melanoma following surgical
      resection of nodal or distant metastases. Upcoming results of Phase III trials
      will establish the role of active specific immunotherapy for adjuvant treatment
      of patients with resected AJCC Stage III and IV melanoma.

PMID- 7805002
TI  - Medical management of stage IV malignant melanoma. Medical issues.
AB  - BACKGROUND: Stage IV melanoma is defined by TNM staging as any tumor, any node,
      and M1, the presence of distant metastasis. The prognosis of Stage IV melanoma is
      grim. The expectation for 5-year survival is less than 10%. METHODS: The
      experience with single-agent chemotherapy, combination chemotherapy, and high
      dose chemotherapy with autologous bone marrow transplantation support are
      reviewed, as are the results of treatment with interferon and interleukin-2.
      RESULTS: Chemotherapy with single agents yields up to a 20% response rate. More
      aggressive treatments with chemotherapy combinations yield approximately 40%
      responses but have no survival advantage over treatment with single agents.
      Recombinant alpha-interferon yields an objective response rate of approximately
      20%. Results are dose related and require a dose in the range of 12 million U/M2
      for optimal response. The results of treatment with interleukin-2 and lymphokine
      activated killer cells are promising, but the optimal dose and method of
      administration need to be confirmed. The interesting appearance of a vitiligo
      like depigmentation in some patients who respond to treatment seems to be
      associated favorably with survival. Gene transfer therapy opens up a new horizon
      for treatment of metastatic melanoma, and this exciting approach is discussed.
      CONCLUSIONS: The treatment of metastatic melanoma is reviewed, including the
      roles of surgery, radiation therapy, chemotherapy, interferon, interleukin-2,
      vaccines, and gene transfer therapy.

PMID- 7805004
TI  - Food supplements for HIV patients.

PMID- 7805003
TI  - Stage IV malignant melanoma. Psychosocial issues.
AB  - The diagnosis of Stage IV malignant melanoma presents a difficult challenge for
      the patient with cancer, family, and health care providers. All must deal with a
      variety of psychosocial issues that range from the existential to the pragmatic.
      In the past decade an evolution in health care reimbursement methods has
      occurred, resulting in decreased length of stay in acute care facilities. It is
      at the point of hospitalization that patients' increasing needs most often become
      apparent. Physicians, nurses, and hospital social workers face the dilemma of
      providing care and support services in the reality of shrinking resources brought
      about by prospective payment, managed care, and cost containment policies. Health
      care delivery systems strive to meet the needs of patients with cancer through
      case management methods that link patients with a wide variety of medical and
      community resources. A case history is presented to demonstrate the need for
      collaboration among the members of the health care community in order to meet
      patient and family psychosocial needs.

PMID- 7805005
TI  - The RN and LPN skill mix.
AB  - Until a few years ago, patient care in most acute care areas at our tertiary care
      hospital in Alberta was delivered almost exclusively by registered nurses (RNs).
      Many believed their workload included tasks that did not require an RN's
      knowledge and skill levels. Around the same time, the hospital was faced with
      budget constraints. The staffing mix changed in 1991 with the introduction of
      another level of caregiver in the active treatment areas--licensed practical
      nurses (LPNs). The new mix caused problems: many RNs were unaccustomed to
      supervising and delegating to other workers and the primary nursing method for
      delivering patient care no longer worked.

PMID- 7805007
TI  - Canadian legislation governing consent to health treatment.

PMID- 7805006
TI  - Beyond informed consent.
AB  - The issue of informed consent ranks among the most heavily debated topics in
      health care. Nearly all health professionals, at some time in their practice,
      encounter situations in which they question their own involvement and
      responsibility in obtaining a consent for medical treatment. Such situations are
      becoming increasingly common for nurses as the structure of the health care
      system changes and nurses' roles become more diversified. Nurses are wise to try
      to understand the principles involved in informed consent and to recognize the
      potential for dilemmas involving ethics and hospital policies.

PMID- 7805008
TI  - A change for the better.
AB  - Promoting health often means trying to help a client change a long-standing
      health behavior such as smoking, inactivity or poor eating habits. And as any one
      knows who has tried to quit smoking or cut back on calories, many health
      behaviors are highly resistant to change.

PMID- 7805009
TI  - Take a step forward.

PMID- 7805010
TI  - [Adult apprenticeship using the Knowles model].
AB  - In her doctoral studies in adult learning, the author perceived that the
      application of Knowles' theory to the learning abilities of sick and healthy
      adults allowed a better understanding than most other theories. In this model,
      adults develop their knowledge, sense of control, and coping skills as they apply
      to situations of daily living. The reason for this is that adults' learning
      patterns are oriented towards their specific life skills. In fact, individuals
      have a desire to learn what is useful and necessary for their progress. In a
      learning situation, the adults' self-concept and acquired experiences are taken
      into account. The adult becomes the centre of the learning process. Knowles
      teaches educators such as nurses to particularly look at the learning needs of
      adults with existential problems. He insists that these needs be acknowledged and
      satisfied in the "here and now," with emphasis on learning rather than teaching.
      Knowles theory is based on four assumptions relating to the adult learner. These
      assumptions are concerned with self-concept, acquired experience, learning
      ability and benefits achieved by the immediate application of learning. The six
      elements that constitute the thinker's concept are explained in detail. They
      include: the need to know; the learner's self-concept; the role of previous
      experience, the willingness to learn; the motivation to learn; and a teaching
      orientation. Knowles differentiates between the learning patterns of adults and
      youths. Helping adults to learn and helping youths to learn are presented as a
      continuum that takes into account the holistic attributes of adults at any moment
      in their learning pattern.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7805011
TI  - [Entering an institution].
AB  - Changes in the family unit affect all members and in some cases create crisis
      situations. One case in point is the need to institutionalize an elderly parent.
      A situation such as this can disrupt the family and threaten its physical,
      psychological and spiritual stability. In this article, the family unit is an
      open system, with family members providing positive and/or negative feedback
      about the crisis situation. The departure of a loved one can create a sense of
      isolation that can divide the family, if they are left to deal with the crisis on
      their own. Whether they are able to re-establish their own equilibrium or remain
      in a state of instability depends on their coping skills. Some factors that
      influence the coping skills needed in time of crisis include the family's
      realistic perception of the crisis situation; the availability of a support
      system; internal resources; and mechanisms available to re-adapt. The facilitator
      assisting the family through a crisis cannot solve each individual's problems.
      Only the individual family member can accomplish this. However, the facilitator
      can intervene by initiating family support systems that help them discover their
      capacity to deal with change in a time of crisis. The facilitator acts as a
      mirror through which family members see their own reflections and find the
      strength to act according to their own capabilities.

PMID- 7805012
TI  - Intershift goes visual.
AB  - The staff of Unit 71, Rockeyview Hospital, Calgary, have developed a visual
      intershift reporting system that has proven to be so satisfactory many hospital
      units have adopted it. Historically, intershift report had been accomplished by
      the outgoing shift taping their report and the incoming shift listening to the
      total report.

PMID- 7805013
TI  - Getting your finances in order.
AB  - Financial success requires two elements--knowing what to do with your money, and
      keeping track of how your investments, income and expenses are doing. Acquiring a
      library of financial planning and investment books is one step towards the
      former, and there are computer software programs on the market that can help take
      the drudgery out of the latter.

PMID- 7805014
TI  - Research, patients and nurses.
AB  - The use of human subjects in research is becoming more of a concern to the public
      and health care professionals. With the advent of experimental drugs, like AZT,
      the conflict between caring for and treating patients versus advancing scientific
      knowledge becomes clear. Nurses asked to assist in research studies are
      particularly concerned when the subjects are their patients.

PMID- 7805015
TI  - Not leaving me.

PMID- 7805016
TI  - Start with nursing care plans.

PMID- 7805017
TI  - Double duty. Interview by Nancy Deutsch.

PMID- 7805018
TI  - In vivo molecular therapy with p53 adenovirus for microscopic residual head and
      neck squamous carcinoma.
AB  - Developing gene therapy strategies may allow contemporary medicine to reassess
      its management of solid malignancies. We have demonstrated previously that the
      wild-type p53 adenovirus (Ad5CMV-p53) suppressed the growth of established tumors
      of the head and neck. In this paper we develop a microscopic residual model which
      mimics the postsurgical environment of head and neck cancer patients with
      advanced disease. Using this squamous cell carcinoma of the head and neck model,
      we prevented the establishment of tumors in nude mice in which tumor cells had
      been s.c. implanted by transiently introducing exogenous wild-type p53 via an
      adenoviral vector 2 days following tumor cell implantation. These effects were
      vector dose dependent but independent on the endogenous wild-type or mutated p53
      status of the cells. Importantly, karyotypically normal and nontumorigenic
      fibroblast cell lines are inert to the p53 adenovirus treatment. These results
      pave the ground work for further development of molecular therapy for head and
      neck cancer and other solid malignancies.

PMID- 7805019
TI  - Characterization of the M(r) 190,000 multidrug resistance protein (MRP) in drug
      selected and transfected human tumor cell.
AB  - Overexpression of multidrug resistance-associated protein (MRP) has been detected
      in resistant cell lines derived from a variety of tumor types. The deduced amino
      acid sequence of MRP suggests that it is a member of the ATP-binding cassette
      transmembrane transporter superfamily that may be glycosylated and/or
      phosphorylated [S. P. C. Cole et al., Science Washington, DC), 258: 1650-1654,
      1992]. Recently, transfection of HeLa cells with MRP expression vectors has
      demonstrated that the protein is capable of increasing resistance to natural
      product drugs such as anthracyclines, Vinca alkaloids, and epipodophyllotoxins
      (C. E. Grant et al., Cancer Res., 54: 357-361, 1994). Although the resistance
      phenotype of the transfectants is similar to that of the human small cell lung
      cancer cell line, H69AR, from which MRP was originally cloned, the transfectants
      differ in their drug accumulation characteristics, relative resistance to certain
      drugs, and MRP mRNA:protein ratio. Such differences have also been observed among
      drug-selected cell lines that overexpress MRP, and the underlying causes of these
      variable phenotypes are presently not known. We have utilized polyclonal anti-MRP
      peptide antibodies to compare MRP post-translational modification, stability,
      processing, and subcellular distribution in the HeLa transfectants and in the
      drug-selected H69AR cells. These studies establish that MRP in both the
      transfected and selected cells is an ATP-binding, integral membrane
      glycophosphoprotein with an apparent molecular weight of 190,000. No obvious
      differences were detected in the extent or type of glycosylation or the kinetics
      of processing and turnover of the protein that might contribute to the different
      characteristics of the transfected and drug-selected cells. Analyses of the
      subcellular distribution of MRP by isopyknic density gradient centrifugation
      revealed that approximately 80% of MRP in the HeLa transfectants was associated
      with a low density plasma membrane fraction while the comparable fraction in the
      drug-selected H69AR cells contained only approximately 50% of the protein. The
      remaining MRP and plasma membrane markers were codistributed in higher density
      fractions consistent with the presence of MRP in endocytotic vesicles. The
      relatively high proportion of MRP associated with these fractions in H69AR cells
      may contribute to the lack of an observable accumulation defect in these cells
      when compared with the transfectants.

PMID- 7805020
TI  - Multistep tumor targeting in nude mice using bispecific antibodies and a gallium
      chelate suitable for immunoscintigraphy with positron emission tomography.
AB  - To improve tumor:tissue ratios in immunoscintigraphy, a three-step targeting
      method has been developed. The reagents used were (a) a radioactive, low
      molecular weight chelate prepared from ionic gallium and a phenolic
      polyaminocarboxylic acid, which can be labeled either with the single-photon
      emitter 67Ga or with the short-lived positron emitter 68Ga (t1/2 = 68 min); (b) a
      bispecific monoclonal antibody (bs-mAb) synthesized from the F(ab)2 fragment of
      the 1.1ASML antibody specific for the glycoprotein CD44v associated with a rat
      pancreas carcinoma cell line and the F(ab') fragment of an antibody specific for
      the gallium chelate; and (c) the nonradioactive gallium chelate covalently
      coupled to transferrin, which served as a high molecular weight blocker to
      prevent binding of the radioactive gallium chelate to bs-mAbs in the circulation.
      Targeting experiments in tumor-bearing nude mice with different doses of bs-mAbs,
      blocker, and 67Ga chelate were adjusted to maximize tumor to tissue contrasts and
      tumor uptake. Compared with the biodistribution of the 131I-labeled, native
      1.1ASML antibody 24 h postinjection, a schedule using 100 pmol bs-mab 24 h later
      100 pmol blocker, 15 min later 16 pmol 67Ga chelate, 1 h later examination,
      increased tumor:blood and tumor: liver ratios by a factor of 5 while keeping the
      localization of radioactivity in the tumor constant (10.1% injected dose/g). High
      contrast images using either 67Ga or 68Ga were obtained within 1 h. The targeting
      method described enables the use of the short-lived positron emitter 68Ga and
      thus allows the combination of an improved immunoscintigraphy and positron
      emission tomography.

PMID- 7805021
TI  - Altered p53 status correlates with differences in sensitivity to radiation
      induced mutation and apoptosis in two closely related human lymphoblast lines.
AB  - Previous work identified TK6 and WTK1 as human lymphoblast cell lines from one
      donor that have different capacities to catalyze recombination and that vary
      significantly in their response to ionizing radiation. WTK1 cells are more
      resistant to the toxic effects of X-rays yet more sensitive to induced mutation.
      We demonstrate here that although both cell lines contain equal levels of p53
      mRNA, baseline protein levels are 4 times higher in WTK1. Irradiation leads to
      higher levels of p53 protein in both lines but to a greater extent in TK6. TK6
      contains a wild-type p53 sequence, while WTK1 has a homozygous mutation in codon
      237 of exon 7. We also observed a significant difference in the kinetics but not
      the overall degree of apoptosis induced by X-rays in these cells; apoptotic death
      is delayed for 3 days in WTK1. We hypothesize that this p53 mutation is
      responsible for the difference in apoptosis as well as for the differences in
      mutability and mutational spectra reported previously.

PMID- 7805022
TI  - Insulin-like growth factor 1 (IGF-1) receptors, IGF-1, and IGF-2 are expressed in
      primary human sarcomas.
AB  - A variety of bone and soft-tissue sarcoma cell lines have been shown to express
      receptors for insulin-like growth factor-1 (IGF-1) and to respond mitogenically
      to IGF-1 in vitro. We have recently demonstrated evidence of IGF dependency in
      murine MGH-OGS and RIF-1 sarcomas, which express relatively high and intermediate
      levels of IGF-1 receptors. Overexpression of IGF-1 receptors and/or IGF ligands
      might, therefore, be a mechanism by which human bone and soft-tissue sarcomas
      obtain a proliferative advantage over normal adjacent tissues. Therefore, we
      evaluated 29 human sarcoma specimens for expression of IGF-1 receptor, IGF-1, and
      IGF-2 by competitive binding and reverse-transcription polymerase chain reaction
      (RT-PCR) techniques. Twelve of 29 sarcomas examined by RT-PCR and 13 of 25
      examined by affinity-binding studies expressed IGF-1 receptor levels equal to or
      greater than levels determined in the IGF-responsive MCF-7 breast carcinoma cell
      line. DNA amplification of the IGF-1 receptor gene was not identified in this
      group of sarcomas that expressed high levels of IGF-1 receptor. Evaluation of IGF
      ligand expression by RT-PCR revealed that 22 of 28 sarcomas expressed IGF-1
      levels comparable to or above those of the RPMI 7666 control line, and 17 of 27
      sarcomas expressed significant levels of IGF-2 compared with the NCI H69 control
      cell line. These results suggest that autocrine/paracrine regulatory mechanisms
      might be responsible for the growth of some sarcomas.

PMID- 7805023
TI  - Genetic evidence for an independent origin of multiple preneoplastic and
      neoplastic lung lesions.
AB  - Patients with a primary cancer in the lung or in the upper aerodigestive tract
      have an increased risk of developing synchronous or metachronous second primary
      lung tumors. This phenomenon has been related to the chronic exposure of the
      bronchial tree to carcinogens through a so-called "field cancerization" process.
      This study was designed to investigate at the somatic level the genetic basis of
      the field cancerization effect in patients having multiple simultaneous
      neoplastic and preneoplastic lesions of the lung. The pattern of specific genetic
      changes occurring with high frequency and in early stages of lung carcinogenesis
      including p53 mutations, deletions of chromosome 3p, and K-ras mutations, was
      investigated by immunocytochemical, cytogenetic, and molecular approaches in 11
      synchronous lesions of five patients with multiple lung cancers. Different
      genetic lesions were observed in all of the pathological specimens analyzed from
      each patient. The pattern of these changes was different both in topographically
      distant or adjacent lesions and in tumors with the same histopathological
      diagnosis supporting their independent origin. The present data provide further
      evidence of the clinical relevance of the field cancerization process, and
      support the use of genetic markers in the differential diagnosis of recurrence or
      metastasis versus second primaries of the lung.

PMID- 7805024
TI  - Transcriptional induction of the melanocyte-stimulating hormone receptor in brain
      metastases of murine K-1735 melanoma.
AB  - Metastatic K-1735 murine melanoma cells are amelanotic in culture or in the
      subcutis of syngeneic mice. When injected into the internal carotid artery, these
      cells produce melanotic brain metastases. The production of melanin in tumor
      cells growing in the brain was directly correlated with induction of melanocyte
      stimulating hormone receptor (MSH-R) steady-state mRNA transcripts. K-1735 cells
      isolated from brain lesions and implanted into the subcutis or grown in culture
      lose MSH-R transcripts and become amelanotic. In contrast to K-1735 cells, B16
      BL6 melanoma cells constitutively produce melanin and express high levels of MSH
      R mRNA regardless of the site of growth. Somatic cell hybrids between K-1735 and
      B16 cells produced melanin and expressed high levels of MSH-R mRNA transcripts,
      regardless of the site of growth, suggesting the dominance of the B16 phenotype.
      Treatment with alpha-MSH failed to upregulate MSH-R expression in cultured K-1735
      cells or to maintain MSH-R expression in K-1735 cells isolated from brain
      metastases to be grown in culture. Responsiveness to alpha-MSH as determined by
      cell proliferation, melanin production, and intracellular accumulation of cyclic
      AMP directly correlated with MSH-R expression. These data demonstrate that a
      specific organ environment influences the phenotype of metastatic cells by
      regulation of specific genes that encode for cell surface receptors.

PMID- 7805025
TI  - Common expression of the tumor marker D-galactose-beta-[1-->3]-N-acetyl-D
      galactosamine by different adenocarcinomas: evidence of field effect phenomenon.
AB  - The simple carbohydrate tumor marker D-galactose-beta-[1-->3]-N-acetyl-D
      galactosamine (Gal-GalNAc) can be easily identified by a sequential galactose
      oxidase (GO)-Schiff reaction either on tissues or on rectal mucus samples from
      patients with colorectal cancer. To check the usefulness of this marker and
      technology in identifying cancers and precancers of other organs, we have
      assessed the differential expression of Gal-GalNAc in various adenocarcinomas and
      their corresponding normal tissues. The expression of Gal-GalNAc determined by GO
      Schiff sequence was examined in a total of 133 tissue samples from 81 cases of
      the adenocarcinomas of the breast, ovary, pancreas, stomach, and endometrium and
      52 cases of respective normal controls. None of the 52 cases of normal tissues
      (except 15 cases of stomach) showed expression of Gal-GalNAc. In contrast, 100%
      of adenocarcinomas from the breast (19 of 19), ovary (15 of 15), and pancreas (6
      of 6), 94.1% of stomach (16 of 17) cancers, and 91.7% (11 of 12) of uterine
      adenocarcinomas expressed Gal-GalNAc. The expression of Gal-GalNAc in cancerous
      tissues was mostly strong and widespread and was distributed in both secreted
      mucin and cytoplasmic mucin droplets. The normal epithelia and their secretions
      in the vicinity of the carcinoma (within the "field") in the breast, bronchus,
      endometrium, and pancreatic duct also expressed Gal-GalNAc in contrast to normal
      tissues obtained from noncancerous individuals, which were totally nonreactive.
      It is concluded that the tumor marker Gal-GalNAc recognized by GO-Schiff sequence
      was highly expressed not only by a variety of adenocarcinomas but also by the
      apparently normal-appearing epithelia and their secretions in the vicinity of
      carcinomas, strongly suggesting a field effect phenomenon of carcinogenic
      agent(s). Identification of the marker in these secretions may have great
      potential in our strategies for mass screening for those cancers.

PMID- 7805026
TI  - Cyclocreatine accumulation leads to cellular swelling in C6 glioma multicellular
      spheroids: diffusion and one-dimensional chemical shift nuclear magnetic
      resonance microscopy.
AB  - Cyclocreatine, an analogue of creatine, inhibits tumor cell proliferation in
      vitro and in vivo. The effects of cyclocreatine in large C6 glioma multicellular
      spheroids were mapped here by magnetic resonance microscopy. Diffusion-weighted
      images of C6 glioma spheroids resolved the bright viable rim and the dark
      necrotic center. Sequential sets of diffusion images, following cyclocreatine
      administration, showed increasing self-diffusion coefficients of the
      intracellular water in the viable rim (0.49 x 10(-5) cm2/s for untreated
      spheroids, 0.62 x 10(-5) cm2/s after 48 h perfusion with 20 mM cyclocreatine).
      This fact correlated with cellular swelling apparent in histological sections.
      The radial distribution of cyclocreatine and soluble lipids across perfused C6
      spheroids was measured by one-dimensional chemical shift imaging. Cyclocreatine
      accumulation was prominent throughout the viable cell layer, with no
      cyclocreatine accumulation in the necrotic center. In both cyclocreatine-treated
      and control spheroids the lipid signal was highest in the necrotic center and
      lower in the inner viable cell layer.

PMID- 7805027
TI  - Spontaneous melanoma formation in nonhybrid Xiphophorus.
AB  - Melanoma in hybrids of Xiphophorus is due to the unrestricted activity of a
      cellular oncogene locus, Tu, encoding the growth factor receptor gene Xmrk. In
      nonhybrid parental fish, Tu is controlled by a tumor suppressor gene. Thus, its
      restricted activity leads there only to a nonmalignant, species- and population
      specific macromelanophore spot pattern. Prompted by enigmatic reports on
      nonhybrid Xiphophorus with pigmentation abnormalities resembling melanoma, we
      have studied pigmentation in descendants of wild-caught fish and purebred
      laboratory stocks derived from wild populations. Whereas most stocks exhibiting
      macromelanophore patterns never developed pigmentation abnormalities, an
      exceptional situation for some nonhybrids was found. In X. variatus carrying the
      macromelanophore pattern "punctatus-2" and in X. cortezi with "spotted caudal,"
      expressivity of the pigmentation gene ranges from a few black spots to extreme
      melanosis and eventually to malignant melanoma. In X. maculatus with the mutant
      pigmentation gene striped" carrying in addition the micromelanophore pattern
      "anal fin black" or "lower comet," testosterone-dependent melanoma develop
      originating from the corresponding micromelanophore pattern. The tumors are
      highly malignant and express a melanoma-associated antigen. Overexpression of the
      Xmrk oncogene appears as the underlying molecular mechanism for tumor induction.
      These findings clearly demonstrate that tumors can also develop in purebred wild
      type fish. The classical model for formation of hereditary melanoma in
      Xiphophorus hybrids does not explain the development of melanoma in the absence
      of hybridization. However, their existence gives additional support to the
      reasoning that the Xmrk oncogene associated with the macromelanophore locus is
      potentially injurious.

PMID- 7805028
TI  - p53 and retinoid chemoprevention of oral carcinogenesis.
AB  - We studied p53 protein's pattern of expression, association with retinoid
      response or resistance, and modulation by retinoid intervention in oral
      premalignancy. These p53 analyses were included in a prospective trial of the
      retinoid isotretinoin (1.5 mg/kg/day for 3 months) in 40 patients (45 oral
      premalignant lesions). Seven nonsmoking subjects (eight oral biopsies) were
      included as a control. Protein levels of p53 were determined separately for the
      whole epithelium and the basal, parabasal, and superficial layers. A wide range
      of accumulated p53 protein levels occurred in 40 (89%) of 45 lesions in basal and
      parabasal but not superficial layers. No p53 protein was detected in any normal
      controls. Accumulation of p53 increased in direct association with histological
      grade (P = 0.0004). An inverse relationship occurred between the levels of
      accumulated p53 protein and response to isotretinoin (P = 0.006). High-dose
      isotretinoin did not modulate accumulated p53 protein expression.

PMID- 7805029
TI  - Thrombospondin modulates human breast adenocarcinoma cell adhesion to human
      vascular endothelial cells.
AB  - Thrombospondin (TSP), a M(r) 450,000 cytoadhesive glycoprotein, has been shown to
      potentiate tumor cell metastasis in mice by a mechanism that involves the
      hemostatic system of the host. In this study, the potential involvement of TSP in
      the interaction of human mammary adenocarcinoma MCF-7 cells with human umbilical
      vein endothelial cells (HUVECs) in culture was investigated. Using an ELISA,
      preconfluent HUVECs synthesized 100-fold more TSP than did MCF-7 cells during 24
      h of culture (20 versus 0.2 microgram/10(6) cells). Confocal microscopy localized
      TSP within intercellular junctions between aggregated MCF-7 cells in suspension.
      On adherent cells, TSP exhibited a patchy distribution both on the cell surface
      and in the cytosol. In HUVECs, TSP strongly stained the perinuclear space and was
      also found in association with cytoskeletal microfibrils. Flow cytometric
      analysis indicated the presence of a large number of unoccupied receptors for TSP
      on MCF-7 cells. Binding studies using [125I]TSP demonstrated the presence of 1.6
      x 10(6) sites/cell with an apparent Kd of 28 nM. Attachment of radiolabeled MCF-7
      cells to a TSP-coated substrate and to HUVEC monolayers was inhibited in the
      presence of a polyclonal antibody to TSP (10 micrograms/ml) or increasing
      concentrations (1-10 micrograms/ml) of soluble TSP. Neither nonimmune IgG nor the
      cell adhesion peptide Gly-Arg-Gly-Asp-Ser (100 micrograms/ml) inhibited these
      interactions. Inhibition was also observed with heparin (10 micrograms/ml),
      suggesting the participation of TSP heparin-binding domain(s) and heparin-like
      molecules. In the presence of an excess of soluble TSP or anti-TSP antibody, MCF
      7 cells did not form aggregates in suspension and preformed aggregates were
      readily dissociated by the addition of soluble TSP. These results indicate that
      mammary adenocarcinoma cells use TSP to form aggregates and to attach to human
      endothelial cells. These interactions may have physiological implications during
      the hematogenous spread of tumor cells.

PMID- 7805030
TI  - Presence and instability of repetitive elements in sequences the altered
      expression of which characterizes risk for colonic cancer.
AB  - 50C10 and 52H10 are two DNA clones previously reported by us to be overexpressed
      in human colonic mucosa at high risk for development of colonic tumors. This
      report presents sequencing data that reveal that these clones contain repetitive
      Alu elements. Each Alu sequence is associated with a 3'-oligoadenylate [oligo(A)]
      sequence, which is demonstrated to exhibit instability in human colonic tumors.
      The oligo(A) sequences only decrease in length, unlike microsatellites, which can
      either increase or decrease. Rigorous quantitative analysis of the length of the
      oligo(A) sequence in colonic tumors demonstrates that the standard deviation of
      the length of the sequence in tumors is a function of the mean length; i.e., as
      the oligo(A) sequence becomes progressively shorter, the variance increases. Both
      measurements, therefore, provide a quantitative index of the extent of
      instability in a tissue. Comparison of instability at the oligo(A) loci defined
      by 50C10 and 52H10 to instability at a CA microsatellite upstream of the apoD
      gene, and comparison of an oligo(A) and a CA microsatellite both in the 3'
      untranslated region of the cyclin D1 mRNA demonstrate that instability in a
      tumor, when present, is more prominent for the oligo(A) sequences than for the
      microsatellite (P < 0.0001). This suggests either that the mechanisms that
      generate oligo(A) instability are more penetrant than those that generate
      microsatellite instability, or that the instability at oligo(A) sequences takes
      place earlier in the development of the tumor and is selected for, thus becoming
      more prominent. These features of oligo(A) instability suggest that they may be
      uniquely useful in detecting and quantifying instability in tissues. Further, the
      presence of repetitive sequence elements in loci overexpressed in colonic mucosa
      at risk may be related to an extensive literature that demonstrates that a
      variety of repetitive sequences accumulate in the cellular RNA population during
      carcinogenesis and in tumors. Such RNA sequences could play a mechanistic role in
      tumor development.

PMID- 7805031
TI  - Enhanced photoproduct repair: its role in the DNA damage-resistance phenotype of
      human malignant melanoma cells.
AB  - A fundamental issue in understanding melanoma is to seek the basis for the
      cellular resistance to DNA damaging agents, which is manifested in vivo as
      pronounced tumor resistance to therapeutic agents. The published consensus on
      melanoma has been that exaggerated postreplication recovery (PRR), rather than
      excision repair, underlies the unusual damage-resistance phenotype. We examined
      the resistance to the model DNA damaging agent, UV-C, of subclones derived from a
      human metastatic melanoma cell line. The clones essentially fall into two groups:
      one with normal and the other with enhanced resistance. We exploited this range
      to investigate the interrelationships between replication, transcription, and
      repair of DNA after UV irradiation. Subclones resistant to UV killing were indeed
      found to possess enhanced rates of PRR and were coresistant to cisplatin.
      However, we now report an overall elevation of photoproduct repair in both
      melanoma groups compared to nonmelanoma controls and conclude that this accounts
      for the resistant melanoma phenotype, including that of enhanced PRR. Repair
      enhancement may explain chemoresistance, while loss of efficiency of certain
      functions, such as PRR, due to the intrinsic genetic lability of tumor cells, may
      generate the class of melanoma subclones exhibiting only normal resistance.

PMID- 7805032
TI  - Tumor suppressive role of an androgen-regulated epithelial cell adhesion molecule
      (C-CAM) in prostate carcinoma cell revealed by sense and antisense approaches.
AB  - We recently demonstrated that C-CAM, an epithelial-cell adhesion molecule of the
      immunoglobulin supergene family, could be regulated by androgen and might act as
      a growth repressor during differentiation of the prostatic epithelium. To define
      the role of C-CAM in prostatic tumorigenesis, a tumorigenic human prostatic
      cancer cell line, PC-3, was transfected with an expression plasmid containing C
      CAM1 (a C-CAM isoform). Transfected clones showed significantly lower growth
      rates, reduced anchorage-independent growth, and less tumorigenicity in vivo than
      control cells. Furthermore, transfection of an antisense vector into a
      nontumorigenic prostatic epithelial cell line, NbE, resulted in tumor formation
      in nude mice. Sublines derived from these NbE-induced tumors had lower levels of
      C-CAM than did control cells. These data suggest that C-CAM1 can function as a
      tumor suppressor in prostate tumorigenesis.

PMID- 7805033
TI  - Homozygous deletions of the multiple tumor suppressor gene 1 in the progression
      of human astrocytomas.
AB  - The multiple tumor suppressor gene 1 (MTS1) located on chromosome 9p has recently
      been implicated as a candidate tumor suppressor gene in many different tumor
      types. Cytogenetic analysis and deletion mapping studies have revealed that
      deletion of chromosome 9p occurs in a significant number of primary human
      astrocytomas. Using multiplex PCR with primers for exon 2 of MTS1 and for D9S196
      from chromosome 9q, we have analyzed 78 primary astrocytic tumors for the
      deletion of MTS1. After controlling for the contamination of tumor samples with
      normal cells, homozygous loss of MTS1 was found in 13 of 25 anaplastic
      astrocytomas (WHO grade III) and in 27 of 46 cases of glioblastomas (WHO grade
      IV) but in none of seven astrocytomas (WHO grade II). These data suggest that
      MTS1 is an important tumor suppressor gene in the malignant progression of
      astrocytomas.

PMID- 7805034
TI  - Translocation t(12;16)(q13;p11) in myxoid liposarcoma and round cell liposarcoma:
      molecular and cytogenetic analysis.
AB  - Translocation t(12;16)(q13;p11) is regarded as a diagnostic marker for myxoid
      liposarcoma. Cytogenetic data on round cell liposarcomas and combined myxoid and
      round cell tumors is scarce, and the genetic basis of progression of myxoid
      tumors to high grade, round cell lesions is unknown. We have accumulated six
      round cell, four combined myxoid and round cell, and three myxoid liposarcomas
      for analysis. t(12;16)(q13;p11) was present in three round cell lesions and was
      detectable in all of the tumors by DNA analysis. In each tumor type, the CHOP
      gene in 12q13 was rearranged and fused to the TLS gene in 16p11. A variant TLS
      CHOP RNA transcript was detected by polymerase chain reaction but did not
      correlate with clinicopathological data. No distinguishing cytogenetic or
      molecular markers for round cell or mixed lesions were found. The histogenic and
      genetic relatedness of myxoid and round cell liposarcomas is apparent from these
      data.

PMID- 7805035
TI  - Microsatellite instability and other molecular abnormalities in non-small cell
      lung cancer.
AB  - Microsatellites are highly polymorphic, short-tandem repeat sequences dispersed
      throughout the genome. Instability of these repeat sequences at multiple genetic
      loci may result from mismatch repair errors and occur in hereditary nonpolyposis
      colorectal carcinoma and certain sporadic cancers. In non-small cell lung cancer,
      we found that microsatellite instability was infrequent, affecting only 7 (6.5%)
      of 108 cases. Despite being observed in all histological subtypes and at
      different tumor stages, microsatellite instability most commonly affected only
      one of the six loci tested on five chromosomal arms. In addition, microsatellite
      instability was associated with extensive, concurrent molecular changes including
      K-ras and p53 mutations as well as frequent loss of heterozygosity at chromosomal
      regions 5q, 8p, 9p, 11p, and 17p.

PMID- 7805036
TI  - Endometrial polyps with predominant stromal component are characterized by a
      t(6;14)(p21;q24) translocation.
AB  - Cytogenetic investigation of endometrial polyps revealed the presence of a
      t(6;14)(p21;q24) as the sole abnormality in three cases. All tumors showed a
      histopathological pattern of predominant stromal hyperplasia with scarce
      representation of glandular elements, suggesting that a cytogenetic subgroup
      characterized by the t(6;14) translocation can be associated with endometrial
      polyps with a preponderant component of mesenchymal origin.

PMID- 7805037
TI  - The novel activation of ABL by fusion to an ets-related gene, TEL.
AB  - In human leukemia, activation of the ABL proto-oncogene locus on chromosome 9
      most commonly occurs as a result of its fusion to the BCR locus on chromosome 22.
      The resulting chimeric protein displays an elevated tyrosine kinase activity. We
      have identified a novel activation of ABL which involves a gene located on
      chromosome 12, designated TEL. Like BCR, TEL is fused in-frame with ABL and
      produces a fusion protein with an elevated tyrosine kinase activity when assayed
      in an immune complex. The amino-terminal sequences of TEL encode a helix-loop
      helix motif which may mediate dimerization.

PMID- 7805038
TI  - Epstein-Barr virus in epithelial cell tumors: a breast cancer study.
AB  - The human herpes virus Epstein-Barr (EBV) is clearly associated with African
      Burkitt's lymphoma and the undifferentiated from of nasopharyngeal carcinoma,
      although its role in oncogenesis is still poorly defined. Recently EBV has been
      implicated in other types of lymphomas, as well as in some nonlymphomatous
      neoplastic processes. Its possible association with human breast cancer has been
      investigated here. DNA from 91 cases of breast carcinoma and blood samples from
      the same patients were amplified with the PCR over a region in the EBV BamHIW
      major repeat sequence following a single-step amplification protocol. Nineteen
      samples (21%) were found to be positive; 10 samples of blood (only 3 of them from
      patients with EBV-positive tumors) were found by the adopted protocol to contain
      EBV DNA. Another series of PCR amplifications using primers covering a unique
      (nonreiterated) fragment in BamHIC encoding the EBERs (two short
      nonpolyadenylated RNAs generally highly expressed in cells latently infected with
      EBV) confirmed these findings. A good correlation between the two sets of
      experiments was observed, and only five differences in results were obtained on
      samples tested. In situ hybridization was carried out using BamHIW biotinylated
      DNA probes or EBER-1 digoxigenin-labeled riboprobes with the aim of confirming as
      well as localizing the signal to the epithelial cell. Twelve sections (63%) among
      the PCR-positive samples were found positive by in situ hybridization with the
      DNA probe, and six (31.5%) sections were found with the RNA probe. Twenty-one
      samples from benign breast tumors or normal breast tissue were used as controls
      for PCR amplification in this study, none of which was found positive. This is
      the first known report showing positive results for EBV in breast cancer. No
      statistical association was found in these studies between the presence of EBV
      and the histological type of the tumor, however. Its role therefore remains for
      the moment unknown, as well as does the significance of the association of EBV
      with only a subset of the cases.

PMID- 7805039
TI  - Cellular processing of copper-67-labeled monoclonal antibody chCE7 by human
      neuroblastoma cells.
AB  - Monoclonal antibody chCE7, an internalizing neuroblastoma-specific chimeric
      antibody, was derivatized with the macrocyclic amine ligand 4-[(1,4,8,11
      tetraazacyclotetradec-1-yl)-methyl] benzoic acid tetrahydrochloride and labeled
      with the potential therapeutic nuclide 67Cu. Using pulse labeling and an acid
      elution endocytosis assay, 67Cu-chCE7 was found to be internalized into human
      neuroblastoma (SKN-AS) cells at a similar rate and to a similar extent as 125I
      labeled chCE7. Uptake of 67Cu-chCE7 and 125I-chCE7 into the acid stable
      (intracellular) pool proceeded with similar kinetics during the first 2 h of
      internalization. However, in contrast to 125I-chCE7-loaded cells, at later times
      intracellular radioactivity kept increasing in the case of 67Cu-chCE7-loaded
      cells. It was shown that this effect is due to the intracellular accumulation of
      a low M(r) degradation product consisting of the 67Cu-4[(1,4,8,11
      tetraazacyclotetradec-1-yl)-methyl] benzoic acid complex, possibly with a short
      peptide attached to it. Degradation of both 125I-chCE7 and 67Cu-chCE7 was
      inhibited by chloroquine, indicating endosomal or lysosomal degradation, and a
      43,000 M(r) fragment was found to be the major high M(r) degradation product in
      both cases. Although at times between 4 and 6 h of internalization intracellular
      breakdown of 67Cu-chCE7 was found to proceed more slowly, the major difference
      between the two immunoconjugates resides in the prolonged cellular retention of
      the 67Cu-chCE7 metabolite.

PMID- 7805040
TI  - A prognostic model of recurrence and death in stage I non-small cell lung cancer
      utilizing presentation, histopathology, and oncoprotein expression.
AB  - In order to construct a multivariate model for predicting early recurrence and
      cancer death for patients with stage I non-small cell lung cancer, 271
      consecutive patients (mean age, 63 +/- 8 years) who were diagnosed, treated, and
      followed at one institution were studied. All patients were clinical stage I with
      head and chest/abdominal computed tomograms and radionuclide bone scans without
      evidence of metastatic disease. Pathological material after resection was
      reviewed to verify histological staging. Follow-up documented the time and
      location of any recurrence, was a median 56 months in duration, and was complete
      in all cases. Data recorded included age, sex, smoking history, presenting
      symptoms, pathological description, and oncoprotein staining for erbB-2 (HER
      2/neu), p53, and KI-67 proliferation protein. Immunohistochemistry of oncogene
      expression was performed on two separate archived paraffin tumor blocks for each
      patient, with normal lung as control. All analyses were blinded and included
      Kaplan-Meier survival estimates with Cox proportional hazards regression
      modeling. Data, including immunohistochemistry, were complete for all 271
      patients. Actual 5-year survival was 63% and actuarial 10-year survival was 58%.
      Significant univariate predictors (P < 0.05) of early recurrence and cancer-death
      were: male sex; the presence of symptoms; chest pain; type of cough; hemoptysis;
      tumor size > 3 cm diameter (T2); poor differentiation; vascular invasion; erbB-2
      expression; p53 expression; and a higher KI-67 proliferation index (> 5%). An
      additive oncogene expression curve demonstrated a 5-year survival of 72% for 136
      patients without p53 or erbB-2, 58% for 108 patients who expressed either
      oncogene, and 38% for 27 who expressed both (P < 0.001).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7805041
TI  - Dietary chlorophyllin is a potent inhibitor of aflatoxin B1 hepatocarcinogenesis
      in rainbow trout.
AB  - Epidemiological and experimental evidence indicates a strong relationship between
      diet and cancer. The purpose of this study was to examine the potential of
      chlorophyllin (CHL), a food-grade derivative of the ubiquitous green plant
      pigment chlorophyll, to inhibit experimental carcinogenesis. We report that CHL
      is a potent, dose-responsive inhibitor of aflatoxin B1 DNA adduction and
      hepatocarcinogenesis in the rainbow trout model when fed with carcinogen. CHL
      neither promoted nor suppressed carcinogenesis with chronic postinitiation
      feeding. By molecular dosimetry analysis, reduced aflatoxin B1-DNA adduction
      accounted quantitatively for reduced tumor response up to 2000 ppm dietary CHL,
      but an additional protective mechanism was operative at 4000 ppm CHL. The finding
      of potent inhibition (up to 77%) at CHL levels well within the chlorophyll
      content of some green leafy vegetables may have important implications in
      intervention and dietary management of human cancer risks.

PMID- 7805043
TI  - Attenuation of G2 checkpoint function precedes human cell immortalization.
AB  - We have investigated the hypothesis that attenuation of the G2 checkpoint, which
      delays entry into mitosis in response to damage to DNA and protects against
      clastogenesis, may contribute to the genetic instability of immortal human cell
      lines. IMR-90 normal human fibroblasts displayed stringent G2 checkpoint response
      to gamma-radiation-induced DNA damage. Irradiation with 1.5 Gy induced 98%
      inhibition of mitosis and 79% inhibition of cyclin B1/p34CDC2 kinase activity
      within 2 h. SV40-transformed IMR-90 cells with extended in vitro proliferative
      lifespan and immortal derivative cells displayed significantly less radiation
      induced G2 delay (60-70%) and less inhibition of cyclin B1/p34CDC2 protein kinase
      activity (43-46%) than was seen in normal cells. Two other SV40-transformed lines
      and a fibrosarcoma line displayed a similar attenuation of G2 checkpoint
      function. The attenuation of G2 checkpoint function in SV40 transformed IMR-90
      cells was associated with elevated levels of expression of cyclin B1 (8-fold
      greater) and p34CDC2 (2.5-fold greater). By allowing cells with damaged
      chromatids to enter mitosis, an attenuation of G2 checkpoint function in finite
      lifespan cells may promote the genetic alterations necessary for the conversion
      to immortality.

PMID- 7805042
TI  - Development of a humanized disulfide-stabilized anti-p185HER2 Fv-beta-lactamase
      fusion protein for activation of a cephalosporin doxorubicin prodrug.
AB  - The humanized anti-p185HER2 antibody, humAb4D5-8, has completed Phase II clinical
      trials for p185HER2-overexpressing breast cancer. Here, this antibody is used as
      a building block to engineer a disulfide-linked Fv (dsFv) beta-lactamase fusion
      protein for use in antibody-dependent enzyme-mediated prodrug therapy using
      cephalosporin-based prodrugs. Three Fv variants were designed with an interchain
      disulfide bond buried at the VL/VH interface and secreted from Escherichia coli.
      One variant, dsFv3 (VL L46C VH D101C0, has similar affinity for antigen (Kd = 0.7
      nM) as the wild-type Fv and was used to construct a fusion protein in which beta
      lactamase, RTEM-1, is joined to the carboxy terminus of VH. The dsFv3-beta
      lactamase fusion protein secreted from E. coli efficiently activates a
      cephalothin doxorubicin prodrug (PRODOX, kcat/km = 1.5 x 10(5) s-1 M-1). PRODOX
      is approximately 20-fold less toxic than free doxorubicin against breast tumor
      cell lines SK-BR-3 and MCF7, which express p185HER2 at elevated and normal
      levels, respectively. Prebinding the dsFv3-beta-lactamase fusion protein
      specifically enhances the toxicity level of PRODOX to that of doxorubicin against
      SK-BR-3 but not MCF7 cells. The fusion protein retains both antigen-binding plus
      kinetic activity in murine serum and is cleared rapidly as judged by
      pharmacokinetic analysis in nude mice (initial and terminal half-lives of 0.23
      and 1.27 h, respectively). Development and characterization of the dsFv3-beta
      lactamase fusion protein is an important step toward targeted prodrug therapy of
      p185HER2-overexpressing tumors.

PMID- 7805044
TI  - Cytotoxic activity of chimeric toxins containing the epidermal growth factor-like
      domain of heregulins fused to PE38KDEL, a truncated recombinant form of
      Pseudomonas exotoxin.
AB  - The EGF-like domains of heregulin alpha, beta 1, beta 2, and beta 3 were fused to
      a truncated form of Pseudomonas exotoxin (PE38KDEL), which contains a modified
      carboxyl-terminal sequence, KDEL, that increases that toxin activity. The
      resulting chimeric toxins were produced in Escherichia coli, purified to near
      homogeneity, and shown to be cytotoxic to target cells with very high activity on
      HTB20, N-87 MCF-7, and HepG2 cells; high activity on A431 and MDA-MB468 cells;
      and low activity toward SK-OV3, L929, and KB cells. The fact that cytotoxicity
      did not correlate with the levels of erbB2 expression indicated that another
      receptor in the erb family might be involved. Accordingly, cytotoxicity assays
      were performed on NIH/3T3 cell lines transfected with EGFR, ErbB2, ErbB3, or
      ErbB4. The results indicate that the heregulin toxins target ErbB4 or possibly
      ErbB3 but not ErbB2.

PMID- 7805045
TI  - Relationship of DNA topoisomerase II alpha and beta expression to cytotoxicity of
      antineoplastic agents in human acute lymphoblastic leukemia cell lines.
AB  - The levels of expression of topoisomerase II alpha and topoisomerase II beta were
      investigated in six established cell lines of human childhood acute lymphoblastic
      leukemia (ALL) as a function of doubling time, cell cycle distribution, and of
      sensitivity to the antineoplastic agents Adriamycin and etoposide. The slowest
      growing cell line, ALL-G, was most sensitive to both drugs, whereas the fastest
      growing cell line, ALL-C, was 15.3- and 6.4-fold more resistant than ALL-G to
      Adriamycin and etoposide, respectively. Furthermore, ALL-W, the second most
      rapidly dividing cell line, was most resistant to both Adriamycin (22.8-fold) and
      etoposide (14.1-fold). Expression of topoisomerase II alpha varied inversely with
      doubling time, whereas no correlation was found between topoisomerase II beta
      levels and doubling time. Expression of topoisomerase II beta varied inversely
      with that of topoisomerase II alpha. The level of topoisomerase II alpha
      correlated directly with the percentage of cells in S and G2-M phases, whereas
      topoisomerase II beta expression varied directly with the number of cells in G1.
      An inverse correlation was found between the level of expression of topoisomerase
      II beta and resistance to Adriamycin, whereas a direct correlation was observed
      between the level of expression of topoisomerase II alpha and resistance to
      Adriamycin. Studies with etoposide, although not statistically significant, were
      consistent with the pattern observed with Adriamycin. These findings suggest that
      in ALL cells, cytocidal activity of Adriamycin and etoposide may be mediated, at
      least in part, by topoisomerase II beta.

PMID- 7805046
TI  - Combined radioimmunotherapy and radiotherapy of human colon carcinoma grafted in
      nude mice.
AB  - The effect of combined radioimmunotherapy (RIT) and fractionated external beam
      radiotherapy (RT) was assessed in two human colon cancer xenografts, Co112 and
      LS174T in nude mice. These tumors were selected for being resistant to RIT alone,
      as is usually the case in the clinical situation. Tumor-bearing mice were treated
      with a combination of five X-ray fractions over 5 days followed by RIT with two
      doses of 1.5 mCi 131I-labeled anticarcinoembryonic antigen monoclonal antibody
      F(ab')2. In Co112 and LS174T, RIT alone achieved a regrowth delay similar to that
      of fractionated RT with total doses of 28 and 26 Gy, respectively. In both tumor
      types, an additive therapeutic effect, measured as increased regrowth delay or
      local control, was observed when combining RT of different dose levels with RIT.
      Normal tissue responses were assessed by monitoring acute peak skin reactions and
      blood cell count. Bone marrow depression for the combination treatment was
      similar to that of RIT alone; relative to skin, at equitoxic levels, no mice
      bearing Co112 tumors were locally controlled with a 32 Gy RT dose alone, while
      this RT combined with RIT gave a local control of 100%. These studies show a
      therapeutic benefit when external beam RT is combined with RIT.

PMID- 7805047
TI  - Reversion of the invasive phenotype of transformed human fibroblasts by anti
      messenger oligonucleotide inhibition of urokinase receptor gene expression.
AB  - The receptors for urokinase plasminogen activator were studied in both normal
      human fibroblasts (WI-38 cells) and their SV40-transformed counterpart (VA-13
      cells). We have shown that transformed cells expose 10 times more urokinase
      plasminogen activator receptors (u-PAR) than normal cells. By cross-linking
      aliquots of cell lysates with the aminoterminal fragment of the A chain of u-PA,
      containing the receptor-binding sequence, we have observed a u-PAR concentration
      at focal contacts in both cell lines. Only transformed cells were able to
      efficiently invade the basement membrane Matrigel. Switching off the receptor
      gene expression by the anti-messenger oligodeoxynucleotides strategy abolished
      the invasive properties of transformed cells. The anti-messenger
      oligodeoxynucleotide sequence we have designed inhibited the u-PAR gene
      expression, lowering both the receptor and the receptor mRNA. This indicates that
      overexpression of u-PAR gene is itself responsible for invasivity of transformed
      fibroblasts in our cell model system and that antisense compound therapy may
      prove to be of clinical interest in the control of cancer spreading.

PMID- 7805048
TI  - Treatment of experimental glioblastoma with a human major histocompatibility
      complex nonrestricted cytotoxic T cell line.
AB  - This study investigates a new approach to adoptive therapy of glioblastoma using
      as antitumor effector a potent major histocompatibility complex nonrestricted
      killer clone (TALL-104) established from a patient with acute T-lymphoblastic
      leukemia. The human glioblastoma cell line U-87 MG could be successfully
      engrafted in mice with severe combined immunodeficiency using the i.p.,
      intracerebral, and s.c. routes. The latter model was elected to evaluate therapy
      based on its high reproducibility. Tumor growth in mice engrafted s.c. was
      proportionally associated with splenomegaly and leukocytosis. Multiple transfers
      of lethally irradiated (non-proliferating) TALL-104 cells at the tumor site
      resulted in about 50-70% inhibition of tumor growth as compared to untreated
      mice, with concomitant reduction of splenomegaly and leukocytosis. The antitumor
      effects were inversely proportional to the size of the tumor at initiation of
      therapy, 90-100% inhibition occurring in severe combined immunodeficiency mice
      treated from the day of U-87 MG challenge. Neither splenomegaly nor leukocytosis
      developed in animals in which tumor growth was completely blocked. Stimulation of
      TALL-104 cells with either interleukin 2 or interleukin 12 prior to irradiation
      and adoptive transfer increased the antitumor efficacy of the killer cells to
      about the same extent. The potential usefulness of irradiated TALL-104 cells in
      adjuvant therapy against glioblastomas and other well-localized tumors is
      discussed.

PMID- 7805049
TI  - Total synthesis of sulfated Le(x) pentaosyl ceramide.

PMID- 7805050
TI  - Total synthesis of a modified ganglioside, de-N-acetyl GM2.
AB  - Regio- and stereo-selective glycosylation of a sialyl donor 6 that carries a N
      phthaloyl protecting group at C-5 with a lactosyl acceptor 7 armed with a
      pivaloyl group at O-2a was performed to give the expected glycotrioside 5.
      Subsequent glycosylation of 5 with 2-azido galactosyl donor 4 gave glycotetraosyl
      derivatives 18 and 19. After conversion of 18 into imidates 25 and 26, coupling
      with (2S,3R,4E)-3-O-benzoyl-2-N-tetracosanoylsphingenine (2) was executed to
      afford completely protected ganglioside analogues 27 and 28. Selective cleavage
      of the methyl ester and N,O-deprotection gave the target de-N-acetyl GM2 (1).

PMID- 7805051
TI  - Isolation and purification of feruloylated oligosaccharides from cell walls of
      sugar-beet pulp.
AB  - Cell walls from sugar-beet pulp contain some feruloyl groups linked to the pectic
      neutral side-chains. Enzymic as well as chemical hydrolysis of the pulp yielded a
      series of feruloylated oligosaccharides, which have been purified by Sephadex LH
      20 and Biogel P-2 chromatography in aqueous solvents. Feruloylated arabinose di-,
      tri-, hexa-, hepta-, and octa-saccharides as well as feruloylated galactose
      disaccharides were obtained after hydrolysis of the pulp with a mixture of fungal
      carbohydrases (Driselase). Feruloylated arabinose and galactose monosaccharides
      were obtained through mild acid hydrolyses. Both arabinose and galactose residues
      in the side-chains are feruloylated, 50-55% of the feruloyl groups being linked
      to arabinose residues and 45-50% to galactose residues. It is concluded that 1
      out of 56 arabinose residues and 1 out of 16 galactose residues present as pectic
      side-chains in sugar-beet pulp carry a feruloyl group.

PMID- 7805052
TI  - Structure identification of feruloylated oligosaccharides from sugar-beet pulp by
      NMR spectroscopy.
AB  - 1D NMR (1H and 13C) and 2D NMR spectroscopy have been used to determine the
      structure of feruloylated oligosaccharides obtained by enzymic degradation or
      mild acid hydrolysis of sugar-beet pulp. Feruloylated oligosaccharides derived
      from pectic neutral side-chains containing arabinose or galactose residues were
      identified. In the feruloylated arabinose oligosaccharides, feruloyl groups were
      linked to O-2 of L-Ara f residues. The structure of the feruloylated arabinose
      disaccharide was identified as O-[2-O-(transferuloyl)-alpha-L-Ara f]-(1-->5)-L
      Ara f and that of the feruloylated arabinose trisaccharide as O-alpha-L-Ara f-(1-
      >3)-O-[2-O-(trans-feruloyl)-alpha-L-Ara f]-(1-->5)-L- Ara f. The structure of the
      feruloylated galactose disaccharide was identified as O-[6-O-(trans-feruloyl) 
      beta-D-Gal p]-(1-->4)-D-Gal p. From our results, we suggest that the feruloyl
      groups present in sugar-beet pulp are linked to the arabinofuranosyl residues of
      the main core of alpha-(1-->5)-linked arabinan chains and to the galactopyranosyl
      residues of the main core of beta-(1-->4)-linked type I galactan chains.

PMID- 7805054
TI  - Heparin-like compounds prepared by chemical modification of capsular
      polysaccharide from E. coli K5.
AB  - O-Sulfation of sulfaminoheparosan SAH, a glycosaminoglucuronan with the structure
      ->4)-beta-D-GlcA(1-->4)-beta-D-GlcNSO3(-)-(1-->, obtained by N-deacetylation and
      N-sulfation of the capsular polysaccharide from E. coli K5, was investigated in
      order to characterize the sulfation pattern eliciting heparin-like activities.
      SAH was reacted (as the tributylammonium salt in N,N-dimethylformamide) with
      pyridine-sulfur trioxide under systematically different experimental conditions.
      The structure of O-sulfated products (SAHS), as determined by mono- and two
      dimensional 1H and 13C NMR, varied with variation of reaction parameters.
      Sulfation of SAH preferentially occurred at O-6 of the GlcNSO3- residues. Further
      sulfation occurred either at O-3 or at O-2 of the GlcA residues, depending on the
      experimental conditions. Products with significantly high affinity for
      antithrombin and antifactor Xa activity were obtained under well-defined
      conditions. These products contained the trisulfated aminosugar GlcNSO3-3,6SO3-,
      which is a marker component of the pentasaccharide sequence through which heparin
      binds to antithrombin.

PMID- 7805055
TI  - Sequencing of xyloglucan oligosaccharides by partial Driselase digestion: the
      preparation and quantitative and qualitative analysis of two new
      tetrasaccharides.
AB  - The pentasaccharide (XXG), [formula: see text] obtained from Rosa xyloglucan, was
      converted to two isomeric tetrasaccharides, a and b (Xyl1.Glc3), by mild acid
      hydrolysis. During hydrolysis in 2 M trifluoroacetic acid at 90 degrees C,
      optimal yields of a and b were obtained after 20-40 min. Each tetrasaccharide was
      purified by preparative paper chromatography and high-pressure liquid
      chromatography (HPLC). The two isomers were distinguished by the products of
      their partial digestion with Driselase, which hydrolyses the glucosidic bonds
      sequentially from the non-reducing terminus: a and b yielded cellobiose and Xyl-
      >Glc-->Glc, respectively showing that they were [formula: see text] and [formula:
      see text] respectively. Tetrasaccharide b was chromatographically identical, upon
      HPLC on Dionex CarboPac PA1, with the tetrasaccharide produced from XXG by the
      action of Tropaeolum alpha-D-xylosidase, supporting the proposed structure.
      Xyloglucan oligosaccharides were assayed quantitatively by measurement of the
      yield of isoprimeverose (Xyl-->Glc) after complete Driselase digestion.

PMID- 7805053
TI  - Degradation of feruloylated oligosaccharides from sugar-beet pulp and wheat bran
      by ferulic acid esterases from Aspergillus niger.
AB  - The activity of two forms of ferulic acid esterase (FAE) from Aspergillus niger
      on a synthetic feruloylated substrate (methyl ferulate) and on 11 different
      feruloylated oligosaccharides from sugar-beet pulp and wheat bran was determined.
      The enzymes exhibited different specificities for the various feruloylated
      substrates and were more active on certain substrates of cell-wall origin than on
      methyl ferulate. Both enzymes preferred the arabinose residue to which ferulic
      acid is attached in the furanose form. FAE-I had no clear preference for the type
      of linkage involved between the ferulic acid units and the oligosaccharide chain.
      In contrast, FAE-III had a clear requirement for ferulic acid to be attached to O
      5 of the Ara f ring while no catalysis was observed when ferulic acid was
      attached to O-2. Both enzymes showed maximum activity on feruloylated
      trisaccharides. An increase in the length of the oligosaccharide chain did not
      preclude catalysis, but feruloylated oligosaccharides of a dp > 3 were hydrolysed
      at a reduced rate. Our results support the hypothesis that different kinds of
      ferulic acid esterases exist with different specificities for the oligosaccharide
      chain of the feruloylated substrates.

PMID- 7805056
TI  - Convenient synthetic approach towards C-3 modified methyl beta-lactosides.

PMID- 7805057
TI  - FTIR studies of sodium hyaluronate and its oligomers in the amorphous solid phase
      and in aqueous solution.

PMID- 7805058
TI  - Conformational features of rhamnopyranose derivatives. The molecular structure of
      methyl 2,3,4-tri-O-acetyl-alpha-L-rhamnopyranoside.
AB  - Methyl 2,3,4-tri-O-acetyl-alpha-L-rhamnopyranoside, C13H20O8, M(r) = 304.3, is
      monoclinic, space group C2, with a = 23.619(1), b = 8.2168(5), c = 19.093(1) A,
      beta = 118.72(1) degrees, V = 3249.6(8) A3, Dc = 1.244 g cm-3, mu (MoK alpha) =
      0.97 cm-1 and Z = 8. The structure was refined to R = 0.044 and Rw = 0.039 for
      1969 observed reflections. There are two independent molecules in the asymmetric
      unit. The bond lengths and bond angles of the pyranose rings of the two are in
      good agreement within the limits of error. The molecules have similar
      conformation except for the orientation of one of the acetoxy groups. Each
      molecule is a normal 1C4 chair with Cremer-Pople puckering parameters Q =
      0.557(6) A, theta = 174.6(2) degrees and psi = 144.6(9) degrees for molecule A
      and 0.564(4) A, 177.9(1) degree and 30.8(8) degrees for molecule B, respectively.
      The acetyl groups have the planar, (S)-cis conformation most commonly observed.
      They are oriented with the acetyl planes within +/- 35 degrees of the C-H bond at
      the ring carbon atom to which they are attached.

PMID- 7805059
TI  - Conformations and structure studies of sugar lactones in the solid state. Part I.
      The molecular structure of L-rhamnono- and L-mannono-1,4-lactones.
AB  - The crystal structures of L-rhamnono-1,4-lactone (1) and L-mannono-1,4-lactone
      (2) have been determined by single-crystal X-ray diffraction. Pertinent crystal
      data are as follows: for 1, orthorhombic, space group P2(1)2(1)2(1), a =
      4.8829(2), b = 10.9088(8), c = 13.9758(9) A, V = 734.7(1) A3, Dc = 1.610 g cm-3,
      Z = 4, R = 0.028 and Rw = 0.035 for 1586 reflections. The lactone ring of 1
      adopts an envelope conformation, E3, slightly distorted toward 2T3, with psi =
      103.1(7) degrees and q = 0.38(3) A, whereas the lactone ring of 2 adopts a
      perfect envelope E3 conformation, with psi = 106.6(4) degrees and q = 0.42(4) A.
      Molecules of 1 and 2 are linked in their crystals through a three dimensional
      network of O-H ... H hydrogen-bonding interactions that involves all hydroxyl
      groups as well as the carbonyl oxygen atom.

PMID- 7805060
TI  - Conformations and structure studies of sugar lactones in the solid state. Part
      II. The molecular structure of alpha-D-glucosaccharino-gamma-lactone: 2-C-methyl
      D-ribo-pentono-1,4-lactone.
AB  - The crystal structure of 2-C-methyl-D-ribo-pentono-1,4-lactone (alpha-D
      glucosaccharino-gamma-lactone, 1) has been determined by single-crystal X-ray
      diffraction. The crystals are orthorhombic, space group P2(1)2(1)2(1) with a =
      7.7429(6), b = 8.3373(7), c = 11.3258(7) A, V = 731.1(2) A3 (CuK alpha, lambda =
      1.54184 A), mu = 10.82 cm-1, Dc = 1.473 g cm-3, and Z = 4. The structure was
      refined to R = 0.0307 and Rw = 0.0424 for 876 observed reflections. Compound 1
      has the D-ribo configuration, in agreement with an earlier deduction from
      chemical evidence. The lactone ring adopts the 3T2 conformation, with puckering
      parameters psi = 279.8(9) degrees and q = 0.32(5) A. The orientation of the
      methyl group about the C-2-C-3 bond is gauche-trans, with the C-6-C-2-C-3-O-3 and
      C-6-C-2-C-3-C-4 torsion angles being -81.3(2) degrees and 154.7(1) degree,
      respectively. The molecules are linked in the crystal in a two-dimensional
      intermolecular hydrogen bonding network that involves all hydroxyl groups as well
      as the carbonyl oxygen atom.

PMID- 7805061
TI  - Selective defucosylation by mercaptolysis. A potential step in analyzing branched
      oligosaccharides.
AB  - A method of stepwise chemical degradation was elaborated on a microgram quantity
      of 3-O-alpha-L-fucosyllactose. The key step, TiCl4-catalysed dithioacetal
      formation from the permethylated N-4-nitrophenyl triosylamine (4) was accompanied
      by quantitative defucosylation. [14C]Acetylation of the dried mercaptalation
      mixture gave radiolabelled 3,5-di-O-[14C]acetyl-4-O-(2,3,4,6-tetra-O-methyl-beta
      D-galactopyranosyl )-2 , 6-di-O-methyl-D-glucose diethyl dithioacetal (7) and 5-O
      [14C]acetyl-2,3,4-tri-O-methyl-L-fucose diethyl dithioacetal (8). The former was
      further degraded via the bis(sulfone), and thereby 2,3,4,6-tetra-O-methyl-D
      galactose (13) was expelled. The monosaccharide branches, fucose and galactose,
      were identified as derivatives 8 and 13, respectively, by comparison with
      authentic samples. Isolation of microquantities of products was carried out by
      preparative TLC.

PMID- 7805062
TI  - Synthesis of neoglycolipids containing a mucin-type core unit.
AB  - The unnatural glycolipids O-beta-D-galactopyranosyl-(1-->4)-O-(2-acetamido- 2
      deoxy-beta-D-glucopyranosyl)-(1-->3)-O-(2-acetamido-2-deoxy-alpha-D-
      galactopyranosyl)-(1-->1)-ceramide (1), O-beta-D-galactopyranosyl-(1-->4)-O-(2
      acetamido-2-deoxy-beta-D-glucopyr anosyl) - (1-->6)-O-(2-acetamido-2-deoxy-alpha
      D-galactopyranosyl)-(1-->1)-ceramid e (2), and O-beta-D-galactopyranosyl-(1-->4)
      O-(2-acetamido-2-deoxy-beta-D- glucopyranosyl)-(1-->3)-O-[O-beta-D
      galactopyranosyl-(1-->4)-(2-acetamid o-2- deoxy-beta-D-glucopyranosyl)-(1-->6)]-O
      (2-acetamido-2-deoxy-alpha-D- galactopyranosyl)-(1-->1)-ceramide (3), and their
      beta-(1-->1)-linked isomers, were synthesized. The precursor oligosaccharides for
      1, 2, and 3 were made by coupling O-2,3,4,6- tetra-O-acetyl-beta-D
      galactopyranosyl)-(1-->4)-3,6-di-O-acetyl-2- deoxy-2-phthalimido-alpha,beta-D
      glucopyranosyl trichloroacetimidate with tert-butyldiphenylsilyl 2-azido-4,6-O
      benzylidene-2-deoxy-beta-D-galactopyranoside, tert-butyldiphenylsilyl 2-azido-3-O
      benzoyl-2-deoxy-beta-D-galactopyranoside, and tert-butyl-diphenylsilyl O-(2,3,4,6
      tetra-O-acetyl-beta-D-galactopyranosyl)-(1-->4)-O-(3,6-di-O-a cetyl-2 - deoxy-2
      phthalimido-beta-D-glucopyranosyl)-(1-->3)-2-azido-2-deoxy-beta- D-
      galactopyranoside, respectively. These oligosaccharides were converted into their
      trichloroacetimidates, which were coupled with 3,2'-di-O-benzoyl ceramide.
      Deprotection of the coupling products gave the title compounds 1, 2, and 3.

PMID- 7805063
TI  - Transglucosylation with 6'-chloro-6'-deoxysucrose and immobilized isomaltulose
      producing microorganisms using 2,2-dimethyl-1,3-dioxolane-4-methanol and its
      related compounds as acceptors. Steric and chemical requirement of the glucosyl
      acceptor.
AB  - Enantioselective and diastereoselective alpha-D-glucosylation of 2,3-O
      isopropylidene-erythritol was observed in transglucosylation with a synthetic
      donor using three kinds of immobilized isomaltulose-producing microorganisms.
      Several related compounds, including an 2,3-O-isopropylidenated aldotetrose
      dimethyl dithioacetal and an aldotetronic acid ester were also glucosylated in
      moderate or good yield, depending on the microorganism utilized. Steric as well
      as functional group factors are discussed in relation to the substrate
      specificity of the glucosyl acceptor.

PMID- 7805064
TI  - Synthetic studies toward pyruvate acetal-containing saccharides: en route to the
      efficient synthesis of Rhizobium-related exopolysaccharide fragments.
AB  - The disaccharide building block benzyl O-(2,3-di-O-benzoyl-4,6-O-[(R)-1
      (methoxycarbonyl) ethylidene]-beta-D-galactopyranosyl)-(1-->3)-2-O-benzoyl-4,6-O
      [(S)-1- (methoxycarbonyl)ethylidene]-alpha-D-glucopyranoside (13), related to a
      Rhizobium exopolysaccharide, was prepared by coupling various 4,6-O-[(R)-1
      (methoxycarbonyl)ethylidene]-D-galactosyl donors (benzoyl-protected chloride 1,
      pivaloyl-protected chloride 2, and benzoyl-protected fluorides 3 and 4, and
      trichloroacetimidate 5) with benzyl 2-O-benzoyl-4,6-O-[(S)-1-
      (methoxycarbonyl)ethylidene]-alpha-D-glucopyranoside (10) and the corresponding
      2,3-O-tetraisopropyldisiloxane-protected glucoside 12. The best results, with
      respect to beta-selectivity and yield of the coupling, were obtained with 5 and
      10 in dichloromethane. The beta-linked (13) and alpha-linked (14) disaccharides
      were efficiently converted via the 1-OH derivatives 17 and 21 into the
      corresponding trichloroacetimidates 18 and 22. The latter were used for the
      synthesis of the disaccharide ligands 4,6-(R)-pyruvate-beta-D-Galp-(1-->3)-4,6
      (S)-pyruvate-beta-D-Glcp-O(CH2) 5NH2 (20), and 4,6-(R)-pyruvate-alpha-D-Galp-(1-
      >3)-4,6-(S)-pyruvate-beta-D-Glcp-O (CH2)5NH2 (24). The corresponding tri- and
      tetra-saccharide derivatives 4,6-(R)-pyruvate-beta-D-Galp-(1-->3)-4,6-(S)
      pyruvate-beta-D-Glcp-(1-->4 )-beta- D-Glcp-O(CH2)5NH2 (28) and 4,6-(R)-pyruvate
      beta-D-Galp-(1-->3)-4,6-(S)-pyruvate-beta-D-Glcp-(1-->4 )-beta- D-Glcp-(1-->4)
      beta-D-Glcp-O(CH2)25NH2 (36) were obtained similarly.

PMID- 7805065
TI  - Structure of the unusual trisaccharide lipopolysaccharide component produced by a
      symbiotically defective mutant of Rhizobium leguminosarum biovar viciae.
AB  - The structure of an unusual trisaccharide component isolated from the
      lipopolysaccharide (LPS) of a Tn5 mutant of Rhizobium leguminosarum biovar viciae
      VF39 which is defective in infection of its host plant has been elucidated. This
      mutant also appears to be defective in the synthesis of a tetrasaccharide
      component normally synthesized by the wild-type organism. The three glycosyl
      components are galactose, mannose, and 3-deoxy-D-manno-2-octulosonic acid (Kdo).
      Mannose is linked to the 5-position and galactose to the 7-position of the 3
      deoxy-2-octulosonic acid residue (Kdo). Both hexosyl components are in the alpha
      pyranosyl form. In the isolated molecule the octulosonic acid appears to be
      present as its gamma-lactone. However, in the lipopolysaccharide molecule, it is
      most likely present in the pyranosyl form. The structure was determined by 1H NMR
      spectroscopy and methylation analysis as well as by fast-atom-bombardment mass
      spectrometry of the peracetylated and per(trideuterio) acetylated
      oligosaccharides. Small amounts of the methylation analysis product of another
      tetrasaccharide different to normal tetrasaccharide component made by the wild
      type organisms were detected. This indicates that in this mutant, there is a
      block in the synthesis of the normal tetrasaccharide component in addition to a
      switch in the synthesis of the LPS type.

PMID- 7805066
TI  - Purification and properties of an exo-(1-->3)-beta-D-galactanase from Aspergillus
      niger.
AB  - An exo-(1-->3)-beta-D-galactanase was purified by six chromatographic steps from
      a culture supernatant of Aspergillus niger. Its apparent molecular mass was 66
      kDa, as estimated by SDS-PAGE analysis. The purified enzyme had no detectable
      activity on various p-nitrophenyl glycosides and on native plant polysaccharides
      but exhibited a high activity on a (1-->3)-beta-D-linked galactan backbone
      obtained after partial acid hydrolysis and two Smith degradations of gum arabic.
      The optimum conditions were pH 4.5 and 40-50 degrees C. The enzyme had a
      Michaelis constant (Km) of 1.9 mg/mL for the beta-(1-->3)-D-galactan with a
      maximum reaction velocity (Vmax) of 1380 nkat/mg. The study of the reaction
      products obtained after enzyme treatment of two galactans derived from gum arabic
      through one or two Smith degradations showed that it was an exo-(1-->3)-beta-D
      galactanase able to by-pass the branching points of galactan backbones and thus
      to release the side-chains of type II arabinogalactans in an undegraded form.

PMID- 7805067
TI  - Analysis of oligosaccharides containing 2-deoxy-alpha-D-arabino-hexosyl residues
      by the reductive-cleavage method.
AB  - A mixture of oligosaccharides containing (1-->4)-linked 2-deoxy-alpha-D-arabino
      hexosyl ("2-deoxyglucosyl") and (1-->4)-linked alpha-D-glucosyl residues (1) was
      analyzed by reduction, permethylation (perethylation), degradation to monomers,
      and GLC-MS. Degradation was performed either by hydrolysis with subsequent
      reduction, by methanolysis, or by reductive cleavage, always followed by
      acetylation. Reductive cleavage turned out to be the method of choice for the
      acid-labile 2-deoxy sugars. The main degradation product formed during acid
      hydrolysis of 2-deoxy-D-arabino-hexosyl residues yielded, after reduction and
      acetylation, (4R,S)-6-O-acetyl-2,3,5-trideoxyhexono-1,4-lactone (7). By
      methanolysis, in addition to the expected methyl glycosides, methyl 2,3,5
      trideoxy-6-O-methyl-4-hexulosonate (12) is formed as a by-product. For
      determination of the distribution of chain lengths, the permethylated oligomers
      were separated by reversed-phase HPLC. For peak assignment, one isolated oligomer
      was investigated by FABMS and 1H NMR spectroscopy. The average degree of
      polymerization (dp) calculated from the HPLC chromatogram is in good agreement
      with the reductive-cleavage results.

PMID- 7805068
TI  - Structure and taste of 4,4',6,6'-tetrachloro-4,4',6,6'-tetradeoxy-alpha, alpha
      galacto-trehalose.

PMID- 7805069
TI  - [The echocardiographic assessment of the functional variations in the left
      ventricle induced by isometric stress in subjects with primary cardiomyopathy in
      the pre-dilated phase].
AB  - The aim of this study was to assess whether a sudden increase in left ventricular
      (LV) afterload in a pre-dilated condition of idiopathic cardiomyopathy, in
      associated with some non-invasively detectable impairment of LV function. Ten
      subjects (Group A, 7 males, 3 females, mean age 36.7 +/- 11.4 years), submitted
      to cardiac catheterization because of severe symptoms related to ventricular
      arrhythmias, were found to have normal coronary arteries and left ventricular
      function, but histological features suggestive of congestive cardiomyopathy at
      endomyocardial biopsy. Echocardiography was performed during handgrip for 5 min
      at 30% of the maximal effort, in order to obtain a sharp increase in systolic LV
      pressure of more than 40 mm Hg. Ten healthy subjects were used as controls (Group
      B). Results in Group A showed a significant decrease in LV ejection fraction
      (from 62.4 +/- 6.9 to 57 +/- 7; p < 0.005) and LV shortening fraction (from 34.2
      +/- 5.1 to 31 +/- 4.3; p < 0.01); a significant increase in LV systolic volume
      (from 48.2 +/- 9.1 to 60.0 +/- 12.0; p < 0.005) and systolic stress (from 114.6
      +/- 33.2 to 178.8 +/- 58.2; p < 0.001). At the first minute of recovery LV
      function normalized quickly while LV systolic volume remained moderately
      increased (52.5 +/- 10.2). In conclusion, in pre-congestive dilated
      cardiomyopathy a latent impairment in LV function can be detected during a sharp
      increase of LV afterload. Isometric stress is particularly useful in eliciting
      these transient changes, as the method allows a reliable echocardiographic
      examination during maximal stress and not only during the recovery phase, as in
      dynamic stress.

PMID- 7805070
TI  - [Cardiovascular adaptation to the stress test in subjects with Cooley's disease].
AB  - Thalassaemia major determines an impaired effort tolerance because of a condition
      of severe anaemia, progressive left ventricular dysfunction, pulmonary
      circulation compromise. The aim of our study is to evaluate haemodynamic response
      to exercise in thalassaemic patients without clinical features of heart failure.
      We have selected 13 patients affected by thalassaemia major (Thal+; 10-18 years).
      Each patient was transfused when haemoglobin values were < 9-9.5 g/dl and was
      treated with desferrioxamine (40 mg/kg sc) when serum ferritin values were >
      2,000 ng/ml. Thal+ patients were compared with normal subjects (Thal- 10-16
      years). No patient assumed hypotensive therapy, no had familiar history of
      hypertension. Both groups have undergone an ergometric stress test at the
      cycloergometer, with increase of 25 W every 2 min, up to the reaching of the
      maximum age-related heart rate, or up to muscle exhaustion or unbearable dyspnea,
      followed by a 10 min recovery phase. The following parameters were taken in
      consideration: systolic (SBP) and diastolic (DBP) blood pressure, heart rate
      (HR), the product of the heart rate by the systolic blood pressure (DP), at rest,
      at the maximum common work (MCW), at maximum stress and in the recovery phases.
      At rest, only DP showed significant differences between the two groups: in Thal+
      patients higher than in Thal- (p = 0.045). At the MCW, Thal+ patients had SBP (p
      = 0.019), DBP (p = 0.01), HR (p = 0.035) and DP (p = 0.003) higher than Thal-
      patients. At maximum stress only DBP showed significant differences in Thal+
      patients (p = 0.019), although Thal+ patients achieved lower levels of workload
      (p = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7805071
TI  - [Multiplane transesophageal echocardiography for the monitoring of cardiac
      surgery].
AB  - Multiplane transesophageal echocardiography (TEE) allows visualization of the
      heart and great vessels through an infinite number of imaging planes and improves
      the diagnostic capabilities of mono and biplane TEE. This study was undertaken to
      test whether MTEE is a useful intraoperative monitoring method during cardiac
      surgery. Intraoperative multiplane TEE was performed in 200 patients (mean age 56
      +/- 19 years) as a part of the routine clinical care. We systematically acquired
      cardiac images from the gastric fundus (short and long axes of the ventricles),
      lower esophagus (four-chamber, two-chamber, and long axis), upper esophagus (13
      views concerning the aorta, pulmonary artery, left and right atrium, systemic and
      pulmonary veins, coronary arteries, right ventricular outflow tract), and
      searched for complete views of the thoracic descending aorta. All views analyzed
      in the preoperative (immediately before cardiopulmonary bypass), intraoperative
      and postoperative phases evaluating: the angle between current and 0 degree at
      which each view was obtained; the success rate of each view; the usefulness of
      the different views in providing essential additional clinical information
      compared to 0 degrees and 90 degrees of the traditional biplane TEE. Most views
      of the heart and great vessels were visualized in oblique planes, and other views
      were significantly improved thanks to slight angle corrections. Multiplane TEE
      was particularly useful in the preoperative and postoperative phases of aortic
      dissection (11 cases), mitral valve repair (13 cases), left ventricular
      aneurysmectomy (9 cases), right atrial thrombosis (1 case), positioning of left
      ventricular hemopump (2 cases), mitral-aortic endocarditis (3 cases), bleeding
      from proximal suture of an aortic heterograft (1 case).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7805072
TI  - [Atrioventricular conduction before and after the radiofrequency catheter
      ablation of a nodal reentry tachycardia circuit].
AB  - Aim of our study was to retrospectively evaluate atrioventricular conduction 24
      hours after selective radiofrequency catheter ablation of the fast pathway or
      after selective ablation of the slow pathway of the atrioventricular nodal
      reentrant tachycardia circuit. Electrophysiologic modifications were
      retrospectively analyzed in 47/48 patients successfully submitted to fast pathway
      ablation and in 90/93 patients successfully submitted to slow pathway ablation.
      The atrioventricular conduction intervals (P-Q and A-H), both anterograde and
      retrograde Wenckebach point, the effective refractory period of atrioventricular
      node and the atrioventricular node function curve were evaluated before and after
      selective radiofrequency catheter ablation of slow and fast pathway. We
      identified the fast pathway ablation potential as: A:V ratio > or = 2:1, His
      electrogram < or = 150 microV. The slow pathway potential was identified as the
      widest, sharpest and latest atrial electrogram recorded during sinus rhythm in
      the posteroseptal region of the atrioventricular junction or as the widest,
      sharpest and earliest observed during retrograde conduction. We observed a
      significant increase in the P-Q and A-H intervals in patients submitted to fast
      pathway ablation, while no significant modification of these parameters was
      appreciated in patients submitted to slow pathway ablation. No significant
      modification of anterograde Wenckebach point (NS) was observed in patients
      submitted to successfully ablation of fast pathway while a statistically
      significant increase in anterograde Wenckebach point (p = 0.03) was observed in
      patients submitted to slow pathway ablation. After selective fast pathway
      ablation, retrograde conduction was absent in 82.9% of patients submitted to
      ablation; in the remaining 17.1% a significant increase of retrograde Wenckebach
      point was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7805073
TI  - [The effects of sublingual nifedipine on isometric stress in patients with severe
      aortic insufficiency. An acute hemodynamic study].
AB  - We studied the acute hemodynamic effects of nifedipine (N) on handgrip test (Hg)
      in 10 patients with aortic regurgitation in II NYHA functional class. In basal
      condition (B) we found a significant increase of mean aortic pressure (AoPmean)
      in all patients after Hg (101 +/- 9.72 versus 110.3 +/- 6.42 mmHg; p < 0.05). Hg
      did not induce significant changes of AoPmean after N. Hg increased left
      ventricular end-diastolic pressure (LVEDP) from 13.3 +/- 6.4 to 20.5 +/- 9.9 mmHg
      (p < 0.01) before N and from 9.7 +/- 3.2 to 12.8 +/- 5.5 mmHg after N (NS). LVEDP
      measured during Hg after N showed lower values than those measured before N (12.8
      +/- 5.5 versus 20.5 +/- 9.9 mmHg; p < 0.01). Cardiac index (CI) increased by Hg
      in B (3.7 +/- 0.7 versus 4.0 +/- 1.1 L/min/m2; NS) and after N (4.5 +/- 0.7
      versus 4.9 +/- 0.9 L/min/m2; NS). CI increased significantly after N at rest (3.7
      +/- 0.7 versus 4.5 +/- 0.7 L/min/m2; p < 0.01) and during Hg (4.0 +/- 1.1 versus
      4.9 +/- 0.9 L/min/m2; p < 0.01). The left ventricular stroke work index (LVSWI)
      decreased during Hg from 74.4 +/- 20.6 to 71.2 +/- 20.0 g.m/m2; NS. N caused an
      increase at rest to 81.4 +/- 22.5 g.m/m2; NS. LVSWI increased significantly
      during Hg to 83.5 +/- 26.2 g.m/m2; p < 0.05. Systemic arterial resistances (SAR)
      significantly decreased after N at rest (1,086.8 +/- 280.8 versus 843.5 +/- 133.1
      dyne.s.cm-5; p < 0.01), but increased in B during Hg to 1,220.9 +/- 350.7
      dyne.s.cm-5; p < 0.05. A significant reduction of SAR values was observed alter N
      during Hg (1,220.9 +/- 350.7 versus 838.9 +/- 139.9 dyne.s.cm-5; p <
      0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7805074
TI  - [Arterial hypertension in the elderly].

PMID- 7805075
TI  - [An accelerated idioventricular rhythm and sports activity. Comments on a
      clinical case and a characterization of the arrhythmia].
AB  - In the evaluation of an accelerated idioventricular rhythm (AIVR) case presented
      by an athlete, even though considered qualified for agonistic sport practice in
      compliance with the COCIS protocol, the authors made some considerations relative
      to such type of arrhythmia. AIVR are characterized by a wide oscillation of
      frequency (from 40 to 120 b/min) and are distinguished as active AIVR when the
      ventricular center exceeds the discharge frequency in a non depressed sinusal
      activity; and it's passive AIVR when an automatic ventricular center substitutes
      the physiological pacemaker in the presence of sinusal bradycardia. This leads to
      think that it could be two different phenomenons. The first is characterized by a
      low frequency and is determined by the activation of some automatic cells located
      under the His bundle, and the second arises with the extrasystolic modality.
      Moreover, AIVR manifest a parasystolic type of behaviour that complicates the
      diagnostic differentiation. Therefore it can be considered that the arrhythmia of
      ventricular genesis (AIVR, ventricular tachycardia, parasystole) represents the
      varied expression of the same electrogenic substratum with different discharge
      potentiality. Thus was formulated the proposal of unifying the ventricular
      rhythms in one group which includes: rhythm of ventricular escapement, AIVR,
      parasystole and ventricular tachycardia.

PMID- 7805076
TI  - Mechanisms of hemostasis and arterial thrombosis.
AB  - The term hemostasis refers to the critical physiologic response to arterial
      injury that serves to limit hemorrhage. Thrombosis, a pathologic process, results
      when the coagulation system is excessively activated in the absence of bleeding.
      The mechanisms that regulate these processes, as well as the mode of action of
      pharmacologic agents that attenuate thrombosis, are discussed.

PMID- 7805077
TI  - Pharmacology of current and future antithrombotic therapies.
AB  - This article reviews the mode of action of pharmacologic agents for anti
      thrombotic therapy. It refers to both clinically established drugs and new
      approaches currently under preclinical or clinical development. Advantages and
      limitations of the different pharmacologic strategies are discussed with special
      attention to their effects on local interaction between the blood and the vessel
      wall.

PMID- 7805078
TI  - Aspirin in the primary prevention of cardiovascular disease.
AB  - The ability of aspirin to reduce cardiovascular disease risks has been tested in
      randomized trials in a wide range of patient categories. There are clear benefits
      of aspirin on nonfatal myocardial infarction, nonfatal stroke, and vascular death
      among patients with prior manifestations of cardiovascular disease, such as
      myocardial infarction, unstable angina, and stroke. Aspirin is also beneficial to
      those in the acute phase of evolving myocardial infarction. In primary
      prevention, there is a clear reduction in myocardial infarction in men. A large
      scale primary prevention trial in women is presently underway.

PMID- 7805079
TI  - Use of antiplatelet agents and anticoagulants in post-myocardial infarction.
AB  - This article addresses the efficacy and safety of antiplatelet and anticoagulant
      agents following acute myocardial infarction. Major trials are reviewed for both
      of these treatment modalities in the order in which they were published.
      Accompanying editorial comments highlight the key findings of the studies and
      places them in historical context. Current recommendations for treatment are
      summarized. Antithrombotic therapy used as an adjuvant to thrombolytic therapy is
      discussed elsewhere.

PMID- 7805081
TI  - Preventing thromboembolism in patients with prosthetic heart valves.
AB  - Despite improvements in valve design, thromboembolic complications remain an
      important complication in patients with heart valve replacement. Less intense
      anticoagulant regimens with or without concomitant antiplatelet therapy have been
      shown to be effective and safe in such patients. The recommended intensity of
      oral anticoagulants for tissue valves is an INR of 2.0 to 3.0 and 2.5 to 3.5 for
      mechanical valves.

PMID- 7805080
TI  - Preventing systemic embolism in patients with abnormal ventricular function.
AB  - Clinical trial results support the aggressive use of anticoagulant therapy to
      prevent systemic embolism in patients with acute myocardial infarction who are at
      high risk for embolism (e.g., anterior transmural infarction). Other patients at
      risk for systemic embolism include those with chronic left ventricular aneurysm,
      chronic dilated cardiomyopathy, and cardiac tumors. The role of antithrombotic
      therapy in these latter groups is incompletely resolved because of a lack of
      clinical trials. However, in view of the devastating consequences of systemic
      embolism, the documented effectiveness of antithrombotic therapy in other high
      risk patients and the improved safety of long-term anticoagulant treatment in
      recent years, it may be prudent to use antithrombotic treatment unless
      contraindicated.

PMID- 7805082
TI  - Preventing systemic embolization in patients with atrial fibrillation.
AB  - Patients with atrial fibrillation have an annual risk of stroke of 4.5%.
      Randomized clinical trials have reliably demonstrated that for every 1000 atrial
      fibrillation patients treated with warfarin, there is a reduction of 31 strokes
      per year at a cost of 3 major bleeds per year (including cerebral hemorrhage).
      Aspirin therapy is also effective for the reduction of stroke, although less so
      than warfarin; the bleeding risk is less with aspirin. It is possible to select
      patients at particularly high risk of cerebral embolism based upon simple
      clinical and echocardiographic parameters. Ongoing clinical trials are evaluating
      regimens of warfarin versus aspirin, combinations of warfarin and aspirin, and
      low-dose warfarin.

PMID- 7805083
TI  - Venous thrombosis: prevention, treatment, and relationship to paradoxical
      embolization.
AB  - Deep venous thrombosis (DVT) is responsible for approximately 200,000
      hospitalizations annually in the United States. DVT is easier and less expensive
      to prevent than to diagnose and treat. For every one million patients undergoing
      surgery who do receive prophylaxis against venous thrombosis, approximately $60
      million will be saved in direct health care costs because effective mechanical
      and pharmacologic modalities are available to prevent most venous thrombi. The
      therapy for DVT should be based upon the anatomic extent of the thrombus as well
      as upon the patient's risk for pulmonary embolism, recurrent DVT, and chronic
      venous insufficiency. In patients with paradoxical embolism, a patent foramen
      ovale, occult leg vein thrombosis (particularly isolated calf vein thrombosis) is
      frequently present.

PMID- 7805084
TI  - Antiplatelet and anticoagulant therapy in patients undergoing percutaneous
      transluminal coronary angioplasty.
AB  - Although coronary angioplasty has been in clinical use for only 15 years,
      continued refinements in technique, instrumentation, and adjunctive therapy have
      led to high initial success rates despite broader patient selection and the
      increasing complexity of lesions attempted. Antiplatelet therapy in the form of
      80 to 325 mg of aspirin begun before the procedure has been demonstrated to be of
      benefit in decreasing the acute complication rate associated with PTCA. In the
      future, this beneficial effect may be augmented by the addition of monoclonal
      antibody inhibitors to platelet membrane glycoprotein IIB/IIIa, possibly at the
      expense of a mild-to-moderate increase in bleeding complications. Although
      routine prolonged antithrombotic therapy has not been useful after uncomplicated
      angioplasty, there is evidence that antithrombotic therapy with heparin for 1 or
      more days before angioplasty will benefit patients with unstable angina or
      evidence of thrombus on angiography. Although patients with thrombus or coronary
      dissection after the procedure probably also benefit from extended heparin
      therapy, most trials have specifically excluded these patients from study. More
      potent and specific antithrombin and antiplatelet agents are currently being
      investigated in human trials and may further lower acute complication rates.
      Although platelets, thrombin, and mural thrombosis have all been implicated as
      factors in restenosis, the process itself remains incompletely understood, and no
      therapy has been shown to be of benefit in humans. The specific platelet IIb/IIIa
      inhibitors, hirudin, hirulog, and factor Xa inhibitors have all shown promise in
      animal models of restenosis, and ongoing or planned trials will define their
      efficacy in humans.

PMID- 7805085
TI  - [What do we mean by the quality of health care?].
AB  - Quality is one of the main features of advanced health care. It is a
      comprehensive concept which comprises specialized technological, interpersonal
      and economic properties of the structure, process and results of provided care.
      The tool for improving the quality is assessment of defined realistic targets and
      systematic monitoring of the quality from all aspects. The prerequisite for
      quality assessment is a clear definition of quality criteria and definition of
      the desirable standards of care. Accreditation of health institutions is a
      suitable method for assessing in a more objective way the quality of health care.
      Obtaining accreditation should imply that the institution works consistently with
      defined standards and manifests a systematic effort to improve provided care and
      services. The optimal position is achieved if accreditation becomes a system of
      eligible dynamic assessment.

PMID- 7805086
TI  - [The mitochondrial genome in medicine].
AB  - Analysis of the mitochondrial genome contributed towards the elucidation of a
      number of deviations-deletions or point mutations in mtDNA which are considered
      the cause of some pathological conditions, usually neuro- and myopathies. The
      distribution of defective mtDNA in the affected organism is uneven not only at
      the tissue or organ level but there are also marked differences between
      individual cells. Maternal heredity assumed for the mitochondrial genome is
      apparent only in some families, frequently also autosomal dominant heredity is
      found.

PMID- 7805088
TI  - [The apomorphine test in the differential diagnosis of Parkinsonism. Initial
      experience].
AB  - BACKGROUND: The reactivity of postsynaptic dopamine receptors in the striatum is
      preserved in Parkinson's disease (PD) but not in parkinsonian syndromes of
      various origin (PS). Hence, the effect of dopaminergic stimulation can serve as
      one of the diagnostic criteria allowing to distinguish between PD and PS. The
      present study aimed to ascertain the clinical utility of Apomorphine (APO), a
      powerful short acting direct D1 and D2 receptors agonist drug, in the
      differential diagnosis of PD and PS. METHODS AND RESULTS: We studied 39 patients
      presenting parkinsonian signs. Based on clinical examination, 23 subjects (7 f,
      16 m, mean age (SD) 59.2 (7.8) years were diagnosed as having probable PD, and 16
      patients (5 f, 11 m, mean age 72 (7.6) yrs, p < 0.001) as having probable PS. In
      the PD group, mean Hoehn and Yahr degree of severity was 2.7 (1.1), mean duration
      of the disease 9.5 (6.2) yrs, mean duration of L-DOPA treatment (20 patients) 6.7
      (5.5) yrs. In the PS group, the respective values of Hoehn and Yahr were 3.3
      (0.9), mean duration of the disease 6.2 (4.1) yrs and mean duration of L-DOPA
      treatment (10 patients) 1.6 (1.1) yrs. After an overnight withdrawal of all other
      dopaminergic medication, a single subcutaneous dose of Apomorphine hydrochloride
      solution corresponding to 0.05 mg per kg of weight was administered. Domperidone
      was given 60 mg daily prior to the testing to avoid undesirable peripheral
      effects of APO. 20 minutes after APO administration, we noted a marked clinical
      improvement i.e. at least 30% decrease of pre-treatment motor score values on
      Columbina University Rating Scale (CURS) in 19 of 23 PD and in one of 16 PS
      patients. In the PD group, the difference between mean CURS values, 30.7 (19.5)
      before and 14.7 (10.3) after APO was highly significant (p < 0.001). In the PS
      group, only a slight posttreatment CURS decrease was found, 39.8 (17.5) before
      and 37.8 (17.5) after APO (p < 0.05). CONCLUSIONS: In individual patients, these
      results mostly confirm the presumed diagnosis of PD or PS. Even in the most
      serious cases from the PD group, the testing showed that the function of dopamine
      receptors in the striatum was still preserved. Thus, the Apomorphine test appears
      to be a helpful tool for differential diagnosis of PD and PS.

PMID- 7805087
TI  - A new classification for mental disorders with management guidelines for use in
      primary care: the ICD-10 PHC.
AB  - A Primary Care Version of International Classification of Diseases (10th
      Revision) Chapter V. for Mental and Behavioural Disorders (ICD-10 PHC) has been
      developed. This version focuses on 24 conditions which are frequently seen in
      primary care and which can be managed effectively by general practitioners. The
      classification is accompanied by flipcards one for each of the conditions. The
      cards contain diagnostic guidelines on one side and management guidelines on the
      other. The latter provide information which should be given to the patient,
      advice on the content of counselling, the available treatment methods, and
      indications for specialist referral. This classification system is also supported
      by diagnostic decision making aids, medication cards, and patient leaflets to
      facilitate the recognition and management of patients in primary care settings.
      The draft ICD-10 PHC will be finalized after the field trials which will test the
      applicability and usefulness of the system in different primary care settings in
      various countries.

PMID- 7805089
TI  - [An unusual paternity dispute case: classical methods did not rule out either of
      the two possible fathers].
AB  - The author described an uncommon case when neither of two men (former husband and
      another man) who were considered possible fathers of the child, could be ruled
      out as potential fathers based on examination of signs of 19 erythrocyte, serum
      and enzyme systems and 59 HLA-A, B, C antigens and their subtypes. The
      eliminating capacity of the examination was 99.86%; paternity was, based on
      probability calculation, practically proved (p = 99.9925% and 99.90%). According
      to statements of parties in the dispute the other man is the child's father. The
      author discusses perspectives of DNA examinations.

PMID- 7805090
TI  - [The right to the truth regarding the end of life--a legal responsibility?].

PMID- 7805091
TI  - [Experiments with hypothermia on prisoners in concentration camps].

PMID- 7805092
TI  - [150 years since the founding of the Journal of the Prague Medical School].

PMID- 7805093
TI  - [Transformation of health care, the aged patient and the aging society].
AB  - Ageing of the population is associated with historically new social conflicts
      which have an immediate impact on the health services. The advances of the health
      care reform depend also on the fact whether the social and health policy will be
      able to foresee these conflicts and tackle them in advance. The most serious
      conflict is the increasing number of old people who require health and/or social
      care with recent medical advances as regards old age, and are confronted with
      final and restricted nation-wide and health resources resp. The author discusses
      possible solutions which in addition to a technical, organizational and economic
      aspect have a significant, although frequently omitted, moral, ethical and
      philosophical dimension.

PMID- 7805094
TI  - [Familial apolipoprotein B-100 defect, a newly discovered lipid metabolism
      disorder].
AB  - Familial defective apolipoprotein B-100 is a newly revealed genetic disorder
      which leads to a rise of atherogenic LDL lipoproteins. It is probably due to the
      replacement of a single amino acid in the huge apoliprotein B-100 molecule, i.e.
      substitution of glutamine by arginine in position 3,500. Thus altered LDL
      lipoproteins are unable to bind with the LDL-receptor. As a result of the
      mentioned metabolic disorder a slightly or markedly elevated plasma cholesterol
      develops which very probably leads to premature manifestation of atherosclerosis.
      The disease is transmitted by autosomal dominant inheritance and its incidence in
      the population is estimated to amount to 1:500, i.e. a similar rate as familial
      hypercholesterolaemia. In the submitted paper some historical facts are presented
      which led to the detection of the disease, methods which are used for its
      detection, and the author presents also results of the first, so still limited
      clinical investigations.

PMID- 7805095
TI  - [Early changes in vascular graft rejection in transplanted kidneys: the past and
      the present].
AB  - BACKGROUND: With maintenance azathioprine+prednisone and in biopsies performed
      exceptionally earlier than in the 4th week (1966-1984, 476 cadaveric kidney
      transplantations), prevalence of obliterative arteriopathy (OA, transmural
      arteritis, 4/III/v3 Banff classif.) was 22.1%, with graft loss by rejection
      within 6 mos. in 89.4%. The aim of this analysis was to study prevalence and
      prognostic importance of the former and of further early vascular lesions in
      subjects with maintenance cyclosporin A using biopsies performed as early as in
      the 1st week. METHODS AND RESULTS: In a retrospective study on 449
      transplantation (1987-92, cyclosporin A+prednisone+azathioprine, 64.7% grafts
      histologically--mostly repeatedly--examined), prevalence and prognostic
      classification (A-good, B-uncertain, C-poor prognosis) in recipients with OA,
      with cellular arteriopathy (CA, intimal arteritis, 4/II-III/v2-v3 Banff classif.)
      and with minimal arterial lesions (MZ) were assessed. Prevalence of OA was found
      to be 7.1% transplantations, with graft loss by rejection within 6 mos. in 71.9%,
      and with A:C proportion 25.0%: 62.5%. CA was found in 5.1% and showed A:C
      proportion 34.7%: 34.7%; in 6/13 cases with repeated histology, OA was later
      encountered, which is a strong point against its humoral pathogenesis. Prevalence
      of MZ was 10.9%, with A:C proportion 40.8: 4.1%. CONCLUSIONS: Both OA and CA are
      related to rejection, while the etiology of MZ remains to be clarified. With
      cyclosporine, prevalence of OA markedly decreased and its prognosis somewhat
      improved; secondary prevention is possible when an early diagnosis (early and
      repeated biopsies) is done and immediate treatment (antilymphocyte globulins)
      started.

PMID- 7805096
TI  - [The role of government in the control of technology research and development].
AB  - It is obvious that government cannot afford to refuse support to precommercial
      general research and development because they would thus deprive their national
      industry of a very important source. The new administration of President Clinton
      emphasized particularly the role of the government in the control of
      technological research and development. The United States wil in future not rely
      on the action of market forces in the commercialization of new innovating
      technologies and shy away from their responsibility. In a recent document
      Technology for America's Economic Growth President Clinton said: "Investing in
      technology is investing into America's future. The traditional support of basic
      science and defence-oriented research only was a strategy suited for previous
      generations, but not for coping with the complicated problems of today. Therefore
      we must focus attention on these new and difficult tasks, being aware that the
      Government can play a key role in the help given to private firms with their
      innovation."

PMID- 7805097
TI  - [Results of training in communication skills at the First Medical School of
      Charles University in Prague].
AB  - Consistent with new trends in medical training the First Medical Faculty, Charles
      University Prague included in its curriculum of general medicine a mandatory
      programme devoted to communication skills. The main objective is to teach
      students to establish valuable contact with the patient and elucidate the problem
      presented by the patient. Another objective is to show the therapeutic potential
      of a well conducted interview. All hitherto trained students who attended the
      classes on communication skills acquired within the repertoire of skills used in
      discussions with patients the skill of a non-directive interview focused on
      elucidation of the problem on which the patient saw his doctor. It proved
      possible to demonstrate that integration of theoretical knowledge into practical
      procedures used in diagnosis, treatment and supportive psychotherapy of somatic
      and psychosomatic diseases and reactive conditions is a relatively demanding and
      long-term process which can be mastered during training which uses acting
      (simulated doctor, simulated patient) and feedback by videorecording.

PMID- 7805098
TI  - [A female patient with near-tetraploid acute myeloid M4 leukemia].
AB  - BACKGROUND: Acute myeloid leukemias (AML) are a heterogeneous group of diseases,
      several types of them are well characterized by typical morphologic, immunologic
      and cytogenetic features of their leukemic blasts in the MIC classification. We
      have recently described 2 patients with a new AML type--poorly differentiated
      near-tetraploid AML L0. The occurrence of very large blasts in a heterogeneous
      blast population seemed to be a morphological sign of this new type of AML.
      RESULTS: The same morphologic characteristics were observed by us when we studied
      blasts of another 80-year-old patient with a near-tetraploid karyotype. However,
      34% of blasts were positive for myeloperoxidase and they exhibited in 24-33%
      surface myelomonocytic markers CD11b, CD13, CD15 and CD14. The illness was
      classified as acute myelomonoblastic leukemia M4 without significant dysplastic
      changes in erythroid and megakaryocytic lineages. The growth of granulocyte
      macrophage bone marrow progenitors CFU-GM was low. The patient refused cytotoxic
      chemotherapy and expired 3 months later on supportive treatment. CONCLUSIONS: The
      finding of very large blasts is a typical sign in cases of near-tetraploid AML.
      Precise classification of leukemia type is essential for successful therapy.

PMID- 7805099
TI  - [Does morality improve health? Psychosomatic thoughts on ethics].

PMID- 7805100
TI  - The heel in sport.
AB  - The various causes of posterior and inferior heel pain in the athlete have been
      presented. Various examples of athletes who have had the various problems and
      discussed their outcome have been discussed. This article primarily has tried to
      educate the reader as to the different types of heel pain and has stressed the
      need for conservative care. Ninety-five percent of patients who have inferior
      heel pain will recover with appropriate conservative care. Therefore, surgery
      should be done only after conservative care has been exhausted and adequate time
      has passed.

PMID- 7805101
TI  - Treatment approaches following foot and ankle injury.
AB  - A complete and effective rehabilitation program begins with a thorough subjective
      and objective evaluation of the problem and injury presented. Biomechanical
      changes, whether they are anatomically induced or as a result of a form of
      compensation, must be identified and properly addressed. During the initial phase
      of rehabilitation, the issues of pain and swelling often must be resolved before
      full range of motion and return to normal strength can be achieved successfully
      during the more advanced stages. It is important to incorporate the entire lower
      quadrant in exercises that are designed to improve proprioception and function,
      using both in open and closed kinetic chain exercises. Finally, the demands to
      which the patient is returning to must be recognized to successfully complete the
      recovery phase.

PMID- 7805102
TI  - Lisfranc injuries in the athlete.
AB  - Injuries to the Lisfranc joint in the athlete comprise a very small proportion of
      tarsometatarsal injuries and are unique in several different ways. The energy
      involved appears to be on a much smaller order of magnitude than more commonly
      encountered injuries leading to obvious fracture and dislocation. Second
      metatarsal subluxation with diastasis between the first and second metatarsal
      tends to be the most commonly encountered injury; however, the true extent of
      injury cannot be based solely on the amount of diastasis present. Lateral weight
      bearing radiographs facilitate evaluation of the normal medial cuneiform-fifth
      metatarsal relationship, which when disrupted indicates an injury more
      significant than a simple sprain and the possible need for open reduction and
      internal fixation. Finally, the restoration of this normal radiographic
      relationship between the medial cuneiform and fifth metatarsal on lateral weight
      bearing views correlates well with the prognosis for achieving an asymptomatic,
      well-functioning foot, allowing a return to a competitive level of athletic
      participation.

PMID- 7805103
TI  - Turf toe injury.
AB  - Long term morbidity secondary to previous first MP injury has been reported by
      Coker and associates and involved persistent pain with athletic activities and
      restricted range of motion. Clanton and coworkers noted hallux valgus and early
      hallux rigidus as specific long term sequelae. Clanton and Seifert have reviewed
      20 athletes with prior turf toe injury with greater than 5 year follow-up noting
      a 50% incidence of persistent symptoms. Further study is needed regarding the
      long term effect of turf toe injury, but it is clearly a significant athletic
      injury that requires appropriate treatment tailored to the severity of the
      injury.

PMID- 7805104
TI  - Chronic leg pain in the athlete.
AB  - Chronic leg pain in athletes results from various conditions. Proper diagnosis
      requires careful examination, knowledge of the various presentations, and
      appropriate use of diagnostic studies. These conditions can often coexist, making
      accurate diagnosis difficult. Most exercise-induced leg pain responds to
      conservative nonsurgical treatment; however, certain syndromes such as chronic
      compartment syndrome or popliteal artery entrapment syndrome are more
      appropriately treated surgically to improve the athlete's ability to return to
      full participation.

PMID- 7805105
TI  - Arthroscopy of the foot and ankle.
AB  - Arthroscopic surgery of the foot and ankle represents a relatively new and
      exciting addition to the armamentarium of the orthopedic surgeon. Direct
      visualization of all intraarticular structures without extensive surgical
      approach, arthrotomy, or malleolar osteotomy is now possible. Laxity or
      incompetency of ligamentous structures can be demonstrated by intraoperative
      stress testing maneuvers.

PMID- 7805106
TI  - Forefoot pain in the athlete.
AB  - Forefoot pain in the athlete is common. Generally, the symptoms are a result of
      overuse. The initial treatment strategy is to modify both exercise and shoewear.
      Specific diagnoses of the problem is key to proper treatment. Usually, the
      history and physical examination are sufficient, but noninvasive as well as
      invasive diagnostic testing may be needed.

PMID- 7805107
TI  - Lateral ankle sprains and instability problems.
AB  - The lateral ankle complex is the most frequently injured single structure in
      athletes, consisting of 38% to 45% of all injuries. One-sixth of all sports
      injury loss time is from ankle sprains. In North America, ankle inversion sprains
      are considered "de rigeur" for basketball participation.

PMID- 7805108
TI  - Achilles tendon disorders.
AB  - In conclusion, the sports medicine specialist is able to use a spectrum of
      diagnostic, surgical, and rehabilitation techniques to identify etiologic factors
      and to choose optimal treatment regimens for patients with Achilles tendinitis or
      traumatic rupture. Correction of pathomechanic factors, anatomic restoration, and
      aggressive postoperative rehabilitation allows an early return to sport without
      significant loss of strength or mobility.

PMID- 7805109
TI  - Dermatologic disorders of the foot.
AB  - This article includes a description of common problems of greatest interest to
      nondermatologist physicians who treat the foot. These include plantar warts,
      corns and callouses, toenail problems, and some common skin disorders, such as
      tinea pedis, pitted keratolysis, hyperkeratosis and fissures, and contact
      dermatitis. Certain neoplasms, including squamous cell carcinoma, verrucous
      carcinoma, and melanoma also are discussed.

PMID- 7805110
TI  - The biomechanics of walking and running.
AB  - An increased knowledge of the biomechanics of normal walking and running will
      improve our understanding of the possible mechanisms of pathology and ultimately
      improve the treatment of pathology and injury. Running, a natural extension of
      walking, involves increased velocities, joint range of motion, forces, muscle
      activity, joint moments, and joint powers as compared with walking. These
      differences not only stress the mechanics of the body to a greater extent but
      also contribute to the development of injury due to overuse. With the use of
      modern computerized gait analysis techniques that provide objective information,
      comprehension of normal and also pathologic walking and running patterns can be
      improved.

PMID- 7805111
TI  - Dance screen programs and development of dance clinics.
AB  - Dance movements can be stressful to the body, and the required extreme positions
      may place physiologic structures at risk for acute, subacute, or chronic injury.
      The authors designed a screening program, conducted by a team of physical
      therapists, orthopedists, and dance instructors, to evaluate dancers for
      musculoskeletal problems and to make recommendations that would improve movement
      compensation, strength, endurance, and mobility.

PMID- 7805112
TI  - Magnetic resonance imaging of the foot and ankle.
AB  - This article describes the application of MR imaging to musculoskeletal imaging,
      specifically, imaging of the foot and ankle. The instrumentation, safety, and
      imaging techniques are discussed with specific attention to fat suppression,
      three-dimensional Fourier transform images, dynamic imaging, magnetization
      transfer contrast, and MR angiography. Normal and abnormal osseous, ligamentous,
      and tendonous anatomy is discussed and illustrated.

PMID- 7805114
TI  - [Relaxing retinectomy: anatomic and functional results].
AB  - The author analyzed the results of relaxing retinectomy (RR) combined with
      internal tamponade of the retina by silicone oil in 50 patients. The causes of
      tractional detachment and shortening of the retina were: proliferative
      vitretinopathy complicating idiopathic rhegmatogenic detachment of the retina in
      25 eyes, proliferative diabetic retinopathy in 12 eyes, post-traumatic
      proliferation in seven eyes, intraocular inflammation in four eyes and the
      cicatricial stage of retinopathy of the premature in two eyes. During an
      observation period of 6-75 months, mean 17 months, the authors recorded complete
      adherence of the retina in 60%, partial anatomical success with defined retinal
      detachment and adherent macula in 24% and functional success with visual acuity
      of 0.02 or better in 66%. The poorest functional results were obtained in
      proliferative diabetic retinopathy (success in 30%). Functional success declined
      with the observation period from 66% 6 months after RR to 38% after 36 months
      following RR. The extent of RR did not have a substantial effect on the
      anatomical and functional results. Sufficiently extensive RR with internal
      tamponade of the retina with silicone oil is the operation of choice in
      complicated retinal detachment where radical membranectomy does not release the
      retinal traction. Reproliferation after RR were the frequent causes of relapses
      of retinal detachment and an impediment for removal of silicone oil from the eye.

PMID- 7805113
TI  - Soft-tissue and bone tumors about the foot and ankle.
AB  - The development of primary and malignant tumors of the soft tissues and bones of
      the foot and ankle are uncommon. A potential for misdiagnosis and increased
      morbidity exists for those patients who do indeed have a malignancy. This article
      illustrates the proper steps in staging lesions and the appropriate techniques
      for biopsy. This will help physicians to avoid undertreating malignant lesions,
      and, conversely, overtreating benign lesions.

PMID- 7805115
TI  - [Personal experience with expanding gases in pars plana vitrectomy].
AB  - At the Second Ophthalmological Clinic in Prague the authors operated between
      January 1991 and November 1993 50 patients, 33 men and 17 women. The mean age of
      the patients was 43.6 years, the minimum observation period 5 months. In all
      patients pars plana vitrectomy was performed (PPV) and at the end of the
      operation or subsequently into the vitreous space the expansive gas SF6
      (hexafluorosulphide) or C3F8 (perfluoropropane) was insufflated. In all instances
      the authors indicated the expansive gas for treatment or prevention of retinal
      detachment and with regard to this they divided the patients into two groups: 1.
      From the total number of 50 patients the authors operated in the first group 31
      patients with complicated retinal detachment (RD). In 17 patient RD with large
      postequatorial tears and traces of blood in the vitreous space were involved. In
      7 patients the cause of RD was a severe eye injury. In five patients the authors
      found a macular opening, in one patient a large postequatorial tear in the
      temporal half and in one patient a circumscribed tractional RD associated with
      diabetic proliferative retinopathy was involved. 2. In the second group of 19
      patients the gas was used as prevention of RD. In 5 patients after transvitreal
      extraction of a foreign intraocular body with suspected or obvious retinal
      defect. In two patients after extraction of a posterior lenticular luxation
      following severe contusion of the eye. In the remaining 12 patients the expansive
      gas was used after removal of silicone oil (SO) and the gas was used at the same
      time to prevent hypotonia of the eye. Anatomical results of surgery. 1. In the
      group of 31 patients with complicated RD after PPV and gas insufflation the
      retina adhered anatomically in 23 patients (74%). In the group with PVR C1-C3 in
      13 patients after gas insufflation the retina became attached in 10 patients
      (76.9%). In one of these patients after three months accentuated cerclage was
      performed because of a new fissure. 2. In the group of 19 patients where gas was
      used for preventive reasons the retina became detached only after removal of SO
      in 5 of 12 patients (42%). Functional results of operation. To assess final
      vision the authors evaluated in the first group a total of 39 patients only after
      gas insufflation and in the second group another 11 patients after reoperation
      with implantation of SO.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7805116
TI  - [The CT image of the eyeball after pars plana vitrectomy using silicone oil for
      internal tamponade of the retina].
AB  - Cerclage and silicon oil induce significant changes in the CT image after the
      vitreous and the retina microsurgery. It is important to get to know the right
      estimation of the CT image. Cerclage has mainly effect on characteristic shape
      changes of eyeball. Hyperdensity shadow of the vitreous cavity in the CT image of
      the eye after silicon oil tamponade creates different physical quality among
      silicone oil, vitreous and aqueous humor.

PMID- 7805117
TI  - [Initial experience with laser therapy of epimacular hemorrhage].
AB  - Epimacular haemorrhage in retinal vascular disease, most frequently in diabetic
      retinopathy, is the cause of sudden substantial deterioration of eye-sight. The
      authors report their initial experience with laser treatment of this
      complication.

PMID- 7805118
TI  - [Problems with secondary implantations of intraocular lenses].
AB  - The authors focus their attention on the problem of secondary implantations of
      posterior chamber lenses. In a group of 20 patients they compare the peroperative
      and postoperative complications of secondary implantation into the sulcus
      ciliaris with and without fixation of the lens.

PMID- 7805119
TI  - [Initial experience with therapy of endogenous uveitis with Consupren--the Czech
      cyclosporin A].
AB  - The authors treated as part of a controlled trial, five patients with Consupren,
      Galen a Co, i.e. the Czech preparation of cyclosporin A. All patients suffered
      from endogenous uveitis which was refractory to treatment with a combination of
      prednisone and cyclophosphamide or prednisone and azathioprin. Mitigation of the
      disease was achieved already during the first three weeks of treatment. In two
      patients during treatment a slight relapse of the inflammation was observed. As
      to side effects of this treatment, the authors observed only once readily
      controllable hypertension and a rise of some indicators of liver metabolism which
      returned to normal already during treatment. Side-effect in conjunction with
      renal affection were not observed in any of the patients. Based on these
      preliminary results the authors assume that Consupren is in the given indication,
      and when the described pattern of administration is used, effective and justifies
      the authors to continue with their investigation.

PMID- 7805120
TI  - [Clinico-histopathologic correlations in cytomegalovirus retinitis in the
      acquired immunodeficiency syndrome].
AB  - The authors describe histological changes of the retina and chorioid in
      cytomegalovirus retinitis in a patient with manifest AIDS who died after a severe
      opportunic infection. Consistent with data in the literature, they describe in
      addition to necrotic changes also inflammatory manifestations in the retina and
      chorioid and the presence of intranuclear inclusions typical for CMV infection.

PMID- 7805121
TI  - [Doppler ultrasonographic velocimetry of the central retinal artery and central
      retinal vein].
AB  - A blood flow rate in the arteria and vena centralis retinae was measured by
      Doppler-ultrasonographic method in a group of 36 patients of an average age of
      59.35 years. The patients did not suffer any cardiovascular disease, glaucoma,
      diabetes mellitus-factors which influence the blood viscosity. In the arteria
      centralis retinae, there was measured a maximum systolic rate of 10.25 +/- 2.66
      cm/s and a end diastolic rate of 5.24 +/- 1.27 cm/s. In the vena centralis
      retinae, there was measured an average maximum flow rate of 5.89 +/- 1.72 cm/s
      and end diastolic rate of 4.1 +/- 1.28 cm/s (minimum 2.12; maximum 6.2 cm/s). A
      procedure of examination and terms of its optimalisation are described there.

PMID- 7805122
TI  - [Confusion between Ophthalmo-Framycoin comp. ung. and cyanoacrylate super glue].

PMID- 7805123
TI  - [Personal experience with the use of Betadine gtt. in the treatment of epidemic
      viral keratoconjunctivitis].

PMID- 7805124
TI  - A new kind of fasciolicide: molecular and electronic structures of some o
      hydroxybenzenesulfonanilides.
AB  - The molecular and electronic structures of some fasciolicidal o
      hydroxybenzenesulfonanilides (HBSA) have been studied using X-ray diffraction and
      semiempirical MO calculation. In these compounds, the phenolic hydroxyl forms a
      strong intramolecular hydrogen bond with an adjacent sulfonyl oxygen atom and the
      strength of the d-p dative S<--N bond, which may control the electron
      delocalization throughout the entire molecule, is affected by substituents on the
      phenyl rings on both sides. Owing to the poor delocalization, the contribution of
      the keto-form of the resonance structure is larger for some phenolate anions of
      HBSA in solution, and this may be a key factor determining the potency of
      fasciolicidal activity of HBSA.

PMID- 7805125
TI  - Resin glycosides. XXI. Tuguajalapins I-X, the resin glycosides having long-chain
      fatty acid groups from the root of Merremia hungaiensis.
AB  - Ten resin glycosides (jalapins) named tuguajalapins I-X were isolated from the
      root of Merremia hungaiensis. Their structures have been determined on the bases
      of chemical and spectral data. Unlike the jalapins so far reported, all of their
      acyl groups consist of two or three long-chain fatty acids, that is, palmitic,
      stearic and/or arachidic acids.

PMID- 7805126
TI  - Antisweet natural products. X. Structures of sitakisosides I-V from Stephanotis
      lutchuensis Koidz. var. japonica.
AB  - From the fresh stem of Stephanotis lutchuensis var. japonica, we have isolated
      five new oleane glycosides named sitakisosides I-V (1-5). Their structures were
      determined on the basis of spectroscopic data and chemical evidence. Sitakisoside
      V showed the strongest antisweet activity among sitakisosides I-V.

PMID- 7805127
TI  - Synthesis and antiallergic activities of 2-alkyl-3,4-dimethylfuro[2,3-c] pyrazole
      5-carboxamides and related compounds.
AB  - A series of 2-substituted 3,4-dimethylfuro[2,3-c]pyrazole- 5-carboxamides and
      related compounds have been synthesized and their antiallergic activities were
      evaluated. Most derivatives with a lower alkyl group at position 2 were orally
      active. Among them, N-ethyl-2,3,4-trimethylfuro[2,3-c]pyrazole- 5-carboxamide
      (III3),2-ethyl-N-methyl-3,4-dimethylfuro[2,3-c]pyrazole-5-ca rboxamide (III14), 2
      isopropyl-N-methyl-3,4-dimethylfuro[2,3-c]pyrazole-5- carboxamide (III27),5-(4,5
      dihydro-5-oxo-1,3,4-oxadiazol-2-yl)-2,3,4- trimethylfuro [2,3-c]pyrazole (IV1)
      and 5-(4,5-dihydro-5-oxo-1,3,4-oxadiazol-2-yl)-2-isopropyl-3,4- dimethylfuro[2,3
      c]pyrazole (IV3) showed promising antiallergic effects. The structure-activity
      relation of these 3,4-dimethylfuro[2,3-c] pyrazole derivatives was examined. An
      amide or 5-oxo-1,3,4-oxadiazole substituent at position 5 was favorable, while
      introduction of a carboxylic acid or acrylic acid moiety was unfavorable.
      However, none of these compounds exerted a significant inhibitory effect on mast
      cell degranulation. Compound III27 and IV3 showed potent anti-allergic activity.
      We found that they also suppressed histamine-, serotonin-, bradykinin- and
      substance P-induced ear edema in mice. In compound 48/80-pretreated mice, the
      preformed mediators in mast cells in the ear were greatly reduced. Under this
      condition, the bradykinin- and substance P-induced ear edema was suppressed by
      compound III27 and IV3 to a significantly greater extent than by diphenhydramine
      combined with methylsergide. These results indicated that the antiallergic effect
      of 3,4-dimethylfuro[2,3-c]pyrazole derivatives probably involves protection of
      the vasculature against the effects of challenge by several mediators.

PMID- 7805128
TI  - Synthesis and structure-activity relationships of new (5R,8S,10R)-ergoline
      derivatives with antihypertensive or dopaminergic activity.
AB  - A series of new (5R,8S,10R)-ergoline derivatives was synthesized, and their
      antihypertensive and dopaminergic activities were evaluated in conscious
      spontaneously hypertensive rats and in rats with unilateral 6-hydroxydopamine
      induced lesions of the substantia nigra, respectively. (5R,8S,10R)-6-Methyl-8-
      ergolinemethanols, prepared from the corresponding ergolinecarboxylates, were
      converted to the tosylates, which were treated with various five-membered
      heterocycles containing nitrogen atoms to afford the new ergolines. (5R,8S,10R)-8
      (1-Imidazolylmethyl)-6-methylergoline (5a, BAM-2101) and (5R,8S,10R)-2-bromo-6
      methyl-8-(1,2,4-triazol-1-ylmethyl) ergoline (7c, BAM-2202) exhibited potent
      antihypertensive activities. The maximum falls of systolic blood pressure after
      oral administration of 5a and 7c at 3 mg/kg were 95 and 132 mmHg, respectively,
      while those of cianergoline, bromocriptine mesylate, hydralazine, and nifedipine
      at the same dose were 40, 37, 47, and 49 mmHg, respectively. The durations of
      significant antihypertensive effects of these compounds except nifedipine were
      more than 7 h. None of the ergolines exhibited potent dopaminergic activity.
      Structure-activity relationships are discussed.

PMID- 7805129
TI  - Pyridonecarboxylic acids as antibacterial agents. VI. Synthesis and structure
      activity relationship of 7-(alkyl, cycloalkyl, and vinyl)-1-cyclopropyl-6-fluoro
      4-quinolone-3-carboxylic acids.
AB  - The title compounds (1a-i) have been synthesized starting with ethyl 1
      cyclopropyl-6,7-difluoro-4-quinolone-3-carboxylate (2). The 7-cyclopropyl and 7
      vinyl derivative (1e and 1i) exhibited potent in vitro antibacterial activities
      against both gram-positive and gram-negative bacteria, being equipotent with
      ciprofloxacin (CPFX) except for the activity against Pseudomonas aeruginosa. The
      two compounds were significantly less toxic than CPFX in terms of convulsion
      induction as determined by intracerebral administration to mice, but showed lower
      urinary recoveries on intravenous administration.

PMID- 7805130
TI  - Pyridonecarboxylic acids as antibacterial agents. VII. Synthesis and structure
      activity relationship of amino- and hydroxyl-substituted 7-cycloalkyl and 7-vinyl
      derivatives of 1-cyclopropyl-6-fluoro-4-quinolone-3- carboxylic acid.
AB  - Novel C(7)-derivatives of 1-cyclopropyl-6-fluoro-4-quinolone carboxylic acid (3a
      o) have been synthesized and evaluated for in vitro antibacterial activity.
      Compounds 3e (3-aminocyclobutyl), 3g (1-aminocyclopropyl), 3m ((2
      aminomethyl)vinyl), and 3o ((1-aminomethyl)vinyl) showed significant inhibitory
      activity, comparable to that of ciprofloxacin, against gram-negative bacteria
      including P. aeruginosa. A good pharmacokinetic profile (serum and brain
      concentrations and urinary recovery) was obtained for the two cyclic compounds
      (3e and 3g), but that of the vinylic compounds (3m and 3o) was less favorable.
      Compound 3g was less toxic than 3e, ciprofloxacin, or ofloxacin in terms of acute
      toxicity and convulsion-induction.

PMID- 7805131
TI  - Pyridonecarboxylic acids as antibacterial agents. VIII. Synthesis and structure
      activity relationship of 7-(1-aminocyclopropyl)-4-oxo-1,8-naphthyridine-3
      carboxylic acids and 7-(1-aminocyclopropyl)-4-oxoquinoline-3-carboxylic acids.
AB  - 4-Oxo-1,8-naphthyridine- and 4-oxoquinoline-3-carboxylic acids (2a, b and 3a-1)
      possessing a 1-amino-cyclopropyl group at the 7-position have been synthesized
      and evaluated for in vitro antibacterial activities. The three quinolones (3d, h,
      i) exhibited potent antibacterial activities against both gram-positive and gram
      negative bacteria, which are comparable to those of ciprofloxacin (CPFX) and
      ofloxacin (OFLX). Among the three compounds, the best pharmacological and
      pharmacokinetic profile was obtained with 3i, an OFLX analogue, which was
      considerably less toxic than three reference quinolones (1, CPFX and OFLX).

PMID- 7805132
TI  - Studies on a novel, potent and orally effective cholecystokinin A antagonist, FK
      480. Synthesis and structure-activity relationships of FK-480 and related
      compounds.
AB  - We prepared various novel tricyclic 1,4-benzodiazepine derivatives as
      cholecystokinin (CCK) A antagonists, which were evaluated preliminarily for
      inhibition of 125I-CCK-8 binding to rat pancreatic membranes in vitro and
      inhibiting effect on CCK-8-induced inhibition of charcoal meal gastric emptying
      in mice. On the basis of structure-activity relationship (SAR) studies, as well
      as the stability and availability of the starting materials of those compounds,
      (S)-N-[1-(2-fluorophenyl)-3,4,6,7-tetrahydro-4-oxo- pyrrolo[3,2,1
      jk][1,4]benzodiazepin-3-yl]- 1H-indole-2-carboxamide (9f, FK-480) was selected as
      a candidate compound for further evaluation. The absolute configuration of the
      precursor of FK-480, (3S)-amino-1,4-benzodiazepine derivative ((S)-8a, R1 = F)
      was determined by an X-ray crystallographic study of its ureido derivative with
      (S)-alpha-methylbenzyl isocyanate. FK-480 is now undergoing clinical studies for
      the treatment of chronic pancreatitis.

PMID- 7805133
TI  - Synthesis and antibacterial activities of 2-oxaisocephems.
AB  - A series of 2-oxaisocephems with a thio-substituted methyl group at the 3
      position and a 2-aminothiazol-4-yl moiety at the 7-position was synthesized via
      benzyl 3-acetyloxymethyl-7-azido-8- oxo-1-aza-4-oxabicyclo[4.2.0]oct-2-ene-2
      carboxylate (2), derived from benzyl acetoacetate (1). The new 2-oxaisocephems
      were tested for antibacterial activities. Among them, the derivatives having a [2
      (2-aminothiazol-4-yl)-2- (Z)-cyclopentyloxyimino]acetamido group at the 7
      position characteristically showed potent activities against gram-positive
      bacteria including methicillin-resistant Staphylococcus aureus (MRSA) and
      Enterococcus faecalis as compared with cefuzonam and cefmenoxime, which are third
      generation cephalosporins.

PMID- 7805134
TI  - Synthesis of artificial glycoconjugates of arginine-vasopressin and their
      antidiuretic activities.
AB  - Arginine-vasopressin (AVP) derivatives modified at the glutamine side chain amide
      with carbohydrate via an alkylene spacer (1a--d) were synthesized from new
      glycosylated glutamine derivatives (3a--d) by solid-phase synthesis.
      Glycoconjugates of AVP modified at the C-terminal amide (2a--d) were also
      synthesized from vasopressionic acid. All of them exhibited antidiuretic
      activity.

PMID- 7805135
TI  - Synthesis and biological activity of new 3-hydroxy-3-methylglutaryl-CoA synthase
      inhibitors: 2-oxetanones with a side chain mimicking the extended structure of
      1233A.
AB  - Structural analogs of 1233A, a microbial metabolite inhibiting 3-hydroxy-3-
      methylglutaryl coenzyme A (HMG-CoA) synthase, were designed and synthesized. The
      2-oxetanone moiety was left intact. All analogs prepared were tested for
      inhibition of HMG-CoA synthase activity and sterol synthesis in mouse liver and
      for effect on serum triglyceride levels. Of these analogs, trans-4-[2-[3-(7
      carboxy-2- naphthyl)phenyl]ethyl]-3-hydroxymethyl-2-oxetanone (4a) showed the
      highest inhibitory activity in vitro, and also had in vivo inhibitory activity
      without causing any increase in triglyceride level.

PMID- 7805136
TI  - Reaction of 6-hydroxytetrahydro-beta-carboline-3-carboxylic acids with
      isocyanates and isothiocyanates.
AB  - The reaction of (-)-(3,S)-6-hydroxy-1,2,3,4-tetrahydro-beta-carboline-3
      carboxylic acid (3a) with isocyanates and isothiocyanates gave the (+/-)-beta
      carboline-hydantoin (4a-d) and -thiohydantoin systems (5a-d). The treatment of (
      )-(1S,3S)-6-hydroxy-1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-ca rbo xylic
      acid (3b) with isocyanates yielded the (+/-)-cis diastereomer of the beta
      carboline-hydantoin rings (4e-h). However, the reaction of 3b with
      isothiocyanates provided the corresponding trans isomer (5e-h). These results
      have been confirmed by 13C-NMR data and nuclear Overhauser effect (NOE)
      experiments. The new compounds were tested for in vitro binding affinity to the
      central-type benzodiazepine receptors.

PMID- 7805137
TI  - Euglobal-In-1, a new euglobal from Eucalyptus incrassata.
AB  - From the juvenile leaves of Eucalyptus incrassata, a new euglobal having an
      acylphloroglucinol-sesquiterpene structure, euglobal-In-1 (1), has been isolated
      along with the known euglobal-III (2) and -V (3). The structure and
      stereochemistry of 1 were established by spectroscopic methods.

PMID- 7805138
TI  - Release of isosorbide dinitrate from polymer film dosage forms and absorption of
      this drug through the oral mucosa of rats.
AB  - In vitro release tests and in vivo absorption measurements of oral cavity dosage
      forms of isosorbide dinitrate (ISDN) prepared from mixed polymer film systems
      were conducted. Hydroxypropylcellulose (HPC) and hydroxypropylmethylcellulose
      phthalate (HPMCP) were used to make the films, and the tests were conducted with
      films made from various ratios of these two polymers. The effects of the addition
      of the accelerator glycyrrhizic acid (GL), on dissolution and absorption were
      also examined. The mean dissolution time (MDT) in the in vitro dissolution tests
      varied with the nature of the polymers and drug, as well as with the pH of the
      testing solution. The MDT for the polymer film system with GL was smaller than
      that without GL. In the in vivo absorption tests using rats, the absorption of
      ISDN through the oral mucosa was observed in all the systems. In the mixed
      polymer film systems, the mean residence time (MRT) increased with increasing the
      ratio of HPMCP/HPC. The values of the area under the curve (AUC) for the systems
      with GL was larger than for those without GL. A good correlation was demonstrated
      between the absorption rate constant, ka and the dissolution rate constant, kd.

PMID- 7805139
TI  - Pheophorbide a, a potent endothelin receptor antagonist for both ETA and ETB
      subtypes.
AB  - Many crude drugs were screened for their capacity to inhibit the binding of
      endothelin-1 (ET-1) to ET receptors; several crude drugs showed significant
      binding inhibitory activity. Pheophorbide a (1), a potent non-peptide ET receptor
      antagonist, was isolated from Altemisiae capillaris Flos ("Inchinko" in
      Japanese), which has been utilized as a remedy for hepatitis in Oriental
      medicine. In receptor binding experiments, compound 1 inhibited ET-1 binding
      specifically to both the ETA receptor (ETAR) and ETB receptor (ETBR), with IC50
      values of 8.0 x 10(-8) and 2.1 x 10(-7) M, respectively. Thus, compound 1 is an
      ET-1 binding inhibitor; however, it exhibited no affinity for the other receptors
      of angiotensin II and atrial natriuretic peptide. We also evaluated the
      inhibitory activity of porphyrin compounds, and found that some exhibited
      moderate activity.

PMID- 7805140
TI  - Further studies on new furostanol saponins from the bulbs of Allium macrostemon.
AB  - Further studies by means of preparative HPLC led to the isolation of two new
      furostanol saponins, macrostemonoside J (1) and L (3), along with an artifact,
      macrostemonoside K (2) from the bulbs of Allium macrostemon. On the basis of
      chemical evidence and spectral analysis (1H-, 13C-NMR and FAB-MS), the structure
      of 1 was elucidated to be 26-O-beta-D-glucopyranosyl 2 beta,3 beta,22,26
      tetrahydroxy-25(R)-5 beta-furostan 3-O-beta-D-glucopyranosyl (1-->2)-beta-D
      galactopyranoside. 3 was deduced to be 26-O-beta-D-glucopyranosyl 2 beta,3
      beta,26-trihydroxy-25(R)-5 beta-furostan- 20(22)-ene 3-O-beta-D-glucopyranosyl (1
      ->2)-beta-D-galactopyranoside.

PMID- 7805142
TI  - New chlorine-containing prenylated C6-C3 compounds increasing choline
      acetyltransferase (ChAT) activity in culture of postnatal rat septal neurons from
      Illicium tashiroi.
AB  - The structures of two new chlorine-containing C6-C3 compounds isolated from the
      woods of Illicium tashiroi have been established as 2(R)-12-chloro-2,3
      dihydroillicinone E (1) and 12-chloroillicinone E (2) by X-ray crystallographic
      analysis and spectroscopic data, respectively. Compound 1 has been found to
      significantly increase ChAT activity in culture of P10 rat septal neurons.

PMID- 7805141
TI  - Pharmacologically active components from a Peruvian medicinal plant, huira-huira
      (Culcitium canescens H. & B.).
AB  - The methanol extract of Huira-Huira (Culcitium canescens) showed analgesic
      effects in acetic acid-induced writhing and tail pressure tests, and it also
      produced potent prolongation of hypnosis induced by pentobarbital. The latter
      activity was used as an isolation-guide to determine the active components which
      were identified as dehydrocacalohastine, cacalohastine and cacalonol.

PMID- 7805143
TI  - Total synthesis of ardisiaquinone A, a potent 5-lipoxygenase inhibitor, isolated
      from Ardisia sieboldii, and degree of 5-lipoxygenase inhibitory activity of its
      derivatives.
AB  - Ardisiaquinone A (1), isolated as a potent 5-lipoxygenase inhibitor from the
      woods of Ardisia sieboldii, has been synthesized efficiently via a cross-coupling
      reaction between the yne 5 and the iodide 6 derived from the common intermediate
      4. Inhibitory activity for 1 and its derivatives is also reported.

PMID- 7805144
TI  - [Research of molecular pathology in carcinoma metastasis].

PMID- 7805145
TI  - [Investigation of EB virus DNA BamHI W fragment, EBNA-2 types and EBNA expression
      in benign and malignant nasopharyngeal biopsies].
AB  - Nasopharyngeal biopsies from 96 cases of clinically suspected nasopharyngeal
      carcinoma and chronic nasopharyngitis were investigated using EB virus DNA BamHI
      W fragment and EBNA-2 A, B type probes. There was a significant dominance of EBV
      EBNA-2 A type infection on all samples: nasopharyngeal carcinoma (NPC) 27/35
      (77.1%), clinically suspected NPC 7/10 (70.0%), chronic nasopharyngitis (CNP)
      18/27 (66.7%). Both W and A probes positive were 20/29 (69.0%) in NPC and 8/25
      (32.0%) in non-NPC, indicating a close relationship between the infection of EBNA
      2 A type virus and NPC in this series. Meanwhile, the expression of EBNA on 35
      cases of biopsy were detected using the anti-complement immunofluorescence
      method, 19/20 (95.0%) were positive in the NPC group and 1/15 (6.7%) in the non
      NPC group. Based on the positive results in detection of A, W or EBNA expression,
      there was a significant difference between NPC and non-NPC groups (P < 0.001). It
      is suggested that EBV infection, especially type A, plays an important role in
      the etiology and pathogenesis of NPC in the Zhanjiang area.

PMID- 7805146
TI  - [The correlation between occurrence of intracranial germ cell tumors and p53
      tumor suppressor gene mutations].
AB  - Using PCR-SSCP molecular biological techniques and sequencing analysis, an
      investigation on intracranial germ cell tumors for a correlation between the p53
      tumor suppressor gene mutations and the occurrence of these tumors was performed.
      The results were as follows: 1. The p53 gene mutations were closely related with
      the development of intracranial germ cell tumors; 2. Among the germ cell tumors,
      different types of tumors had different p53 tumor gene mutations.

PMID- 7805147
TI  - [The application of PCR technique in genetic diagnosis of non-Hodgkin's
      lymphoma].
AB  - In this study, specimens from 59 cases of non-Hodgkin's lymphoma (NHL) were
      immunophenotyped with L26 and UCHL-I McAb, then investigated for gene
      rearrangement by PCR technique. The results showed that the rates of positive
      amplification of clonal IgH and TCR beta gene rearrangement were 71.4% (10/14)
      and 83.3% (10/12) respectively in the fresh tissues, and the IgH (semi-nested PCR
      technique) and TCR beta were 80% (12/15) and 73.3% (11/15) respectively in
      paraffin embedded tissues. Definitive diagnosis was made for the 6 cases which
      could not be diagnosed by routine and immunohistochemical methods, and all 6
      exhibited IgH or TCR beta single band. No cases with pseudopositive amplification
      were discovered. This study suggested that the PCR technique was the most
      specific, sensitive and rapid detection method for clonal gene rearrangement in
      NHL.

PMID- 7805148
TI  - [Detection of T-cell receptor gamma chain V gene rearrangements in
      angioimmunoblastic lymphadenopathy type T-cell lymphoma by PCR and family
      specific primers].
AB  - Using PCR method and family specific primers for T-cell receptor gamma chain V
      gene, the T-cell colonalities of 12 cases of AILD-TCL were analyzed. The results
      showed monoclonal DNA amplification patterns of TCR gamma in all 12 cases (13
      specimens), whereas the DNA from normal peripheral lymphocytes and 2 samples of
      atypical lymphoid hyperplasia showed polyclonal rearrangement patterns. Our
      results suggest that AILD-TCL is a monoclonal proliferative disorder originating
      from T-cell. The PCR method and family specific primers could successfully
      amplicate the template DNA from paraffin sections, so it is a sensitive, simple
      and rapid method for routine hematopathologic studies.

PMID- 7805149
TI  - [The effects of epidermal growth factor and its antibody on the growth of
      xenografts in athymic nude mice].
AB  - Soybean trypsin inhibitor was added to the primary cell culture for establishing
      a novel moderately differentiated human pancreatic adenocarcinoma cell line, PC
      7. The PC-7 cell line was confirmed to be a malignant human pancreatic
      adenocarcinoma by morphological and biological studies. Chromosomal analysis and
      DNA content of PC-7 determined by flow cytometry showed a hypodiploid karyotypic
      pattern. Cultured PC-7 cells were inoculated into the back of athymic nude mice
      to create a transplanted tumor model. The effects of epidermal growth factor
      (EGF) and anti-EGF antiserum on PC-7 transplanted tumor were observed by
      injecting EGF or anti-EGF at the periphery of the solid tumors. In comparing to
      the control group, the tumor weights of the EGF group and the anti-EGF group were
      138% and 67% respectively. Histological and electron microscopic studies higher
      mitotic rate in the EGF group and a lower rate in the anti-EGF group compared to
      the control. The results indicate that EGF stimulated and anti-EGF partially
      inhibited the growth of transplanted PC-7 solid tumors in athymic nude mice.

PMID- 7805150
TI  - [Enzyme cytochemistry and morphometric study of the effects of macrophages on
      A549 pulmonary alveolar cell carcinoma cell line].
AB  - In order to study the mechanism of the effects of M phi on tumor cells, enzyme
      cytochemistry and morphometry were used to investigate the activities of
      cytochrome oxidase (CO), succinate dehydrogenase (SD), lactate dehydrogenase
      (LDH) and acid phosphatase (ACP) in A549 pulmonary alveolar cell carcinoma cells
      which had been interacted with normal and CP-activated macrophages respectively.
      It was found that when E/T = 10:1, the enzyme activity of the cancer cell
      mitochondria, CO, SD, LDH were decreased, and when E/T = 20:1, the activity of
      the lysosomal enzyme ACP was increased. These results indicate that when the E/T
      ratio was appropriate, activated M phi may injure the mitochondria and lysosomes
      and affect the aerobic respiration and oxidative phosphorylation of cancer cells.
      This may be one of the cytostatic and cytotoxic mechanisms of activated M phi on
      tumor cells.

PMID- 7805151
TI  - [A study on HLA-Dr expression of brain tumor cells and mononuclear cell subsets
      infiltrating in these tumors].
AB  - Fourty-four primary brain tumors were studied by immunohistochemistry. 29 (67.2%)
      expressed HLA-Dr. The incidence and number of tumor cells positive for HLA-Dr
      correlated with the histological type of brain tumor and increased with the
      degree of malignancy. The mononuclear cells infiltrating in these tumors were
      mostly CD45ROT cells and macrophages. The former consisted mainly of CD4 and CD8
      subsets. The numbers of CD45RO+ and CD8+ T cells in HLA-Dr-group were more than
      any of the HLA-Dr+, +2, +3 groups. The numbers of CD4 subset and macrophages were
      not affected by the level of HLA-Dr expression. These results suggest that the
      HLA-Dr expressed by brain tumor cells selectively inhibit CD8 subset which
      participates in immunoreaction against brain tumors in situ.

PMID- 7805152
TI  - [The association of Epstein-Barr virus with Hodgkin's lymphoma in childhood].
AB  - Specimens from 82 children with Hodgkin's lymphoma were studied by
      immunohistochemical technique for Epstein-Barr virus encoded latent membrane
      protein (LMP). LMP was demonstrated in 67 cases 81.7%, the positive rate for the
      mixed cellular subtype was 90.9%. The positive rate for the 3-5 year old group of
      patients was 100%, 75% for the 6-10 year old group and only 62.5% for the 11-14
      year old group. These findings suggest that Epstein-Barr virus is strongly
      associated with Hodgkin's lymphoma, the younger the age, the stronger the
      association. Mixed cellular subtype of Hodgkin's lymphoma had the strongest
      association with Epstein-Barr virus among all subtypes.

PMID- 7805153
TI  - [Experimental pathological study of brain damage in rats with copper deficiency].
AB  - Pathological observations on brain damage in baby rats with experimental copper
      deficiency were carried out and the following observations were made: 1. The
      cerebrum were decreased in size and weight, the cortex became thinner and the
      corpus striatum atrophic. 2. Vacuolar degeneration and swelling of the
      mitochondria in the extrapyramidal system within the corpus striatum resulted in
      axon damage and disintegration of the myelin sheath. 3. Proliferation of
      endoplasmic reticulum in the dark neurons, swelling and rupture of mitochondria
      in the light neurons, which can result in necrosis of both types of neurons. The
      damage due to copper deficiency could not be reversed by copper supplements in
      diet.

PMID- 7805154
TI  - [Distribution of rabies antigen in human tongue and salivary gland].
AB  - The distribution of rabies virus antigen (RVAg) in human tongue and salivary
      glands from three cases was studied with ABC immunohistochemical method. Of the 5
      tissue blocks from 2 tongues, large amounts of RVAg were found in 4 tissue
      blocks, located in the serous glands, terminal nerves, some striated muscle
      fibers and some covering epithelium including taste cells of circumvallate
      papillae. Only small amounts of RVAg were present in 4 of the 9 salivary gland
      blocks, either within the acini or in nerves. These results differ from that
      reported previously in dog, fox and skunk salivary glands, which contained
      abundant RVAg. The amount of RVAg in human tongue is apparently greater than that
      in the salivary glands. It is probable that the serous glands of the human tongue
      are sites of predilection for RVAg and may serve as a source of infection.

PMID- 7805155
TI  - [The pathology of Joseph's disease in a Chinese family: a report of two autopsy
      cases].
AB  - This is the first pathology report on Joseph's disease in China, based on
      autopsies of 2 members of the Huang family. The main pathological changes were
      chiefly located in the central nervous system including globus pallidus and Luy's
      body, cerebellar dentate nucleus, cranial nerve motor nuclei of brain stem,
      substantia nigra and red nuclei, and also there were severe loss of neurons in
      the anterior horn and Clarke's nuclei; severe demyelinization of cerebellospinal
      tract and degeneration with demyelinization of the peripheral nerves accompanied
      by neurogenic skeletal muscular atrophy. It is concluded that the pathologic
      characteristics were similar to those found in Europe, United States and Japan.

PMID- 7805156
TI  - [Tay-Sachs disease: a report of 2 autopsy cases].
AB  - Tay-sachs disease (GM gangliosidosis), which is transmitted as autosomal
      recessive trait, is rare in China. Two cases of Tay-Sachs disease were diagnosed
      and treated in PUMC hospital during the past 7 years. The clinical features,
      blood hexosaminidase A level and autopsy findings are presented.

PMID- 7805157
TI  - [Cell adhesion molecules and their role in pathology].

PMID- 7805158
TI  - [Comparison of skeletal development between rural and urban school-age children].
AB  - Skeletal development and other related indicators were measured in 1680 children
      aged 7-18 in urban areas of Harbin and rural areas of Hailun County in 1990-1992,
      and comparisons were made. The results showed that the skeletal age of urban
      children aged 7-17 was higher than that of rural children in both sexes, and this
      difference was significant in the early puberty stage. The difference in mean
      values of cortical thickness of the metacarpals between urban and rural children
      showed similar tendency. Sesamoid ossification in urban children occurred one
      year earlier than that in rural children in both sexes. In primary school-age
      children, skeletal age was highly correlated with body height and weight. The
      development of secondary sex characteristics in both sexes and the age at
      menarche in girls in urban areas were earlier than those in rural areas, and the
      onset of puberty occurred one year earlier in urban than that in rural children.

PMID- 7805159
TI  - [The characteristics of two-dimensional and color Doppler ultrasonography in
      Graves' disease].
AB  - Color Doppler flow imaging (CDFI) was performed in 24 patients with Graves'
      disease, and the results were compared with those from 8 patients with
      Hashimoto's disease, 6 patients with simple diffuse goiter and 15 normal
      volunteers. All cases were confirmed by clinical, laboratory tests or by
      pathology. The CDFI findings of the cases with Graves' disease showed diffuse or
      localized hypoechoes within the glands and rich flow signals in the hypoechoes,
      and acceleration of flow velocity and decrease of resistance in the superior
      thyroid arteries (STA) and arteries within the glands. These appearances were
      characteristic as compared with the controls. The rate of flow in STA of Graves'
      disease cases was 8 to 10 times higher than that in the normal volunteers. This
      study demonstrated that CDFI is convenient, time saving, inexpensive and
      noninvasive as compared with isotope scan and some other laboratory tests, and
      can be widely used in the diagnosis of Graves' disease. The pathologic basis of
      Graves' disease on ultrasonography and its differential diagnosis are discussed.

PMID- 7805160
TI  - [The excitation site of MEP on facial nerve by transcranial magnetic
      stimulation].
AB  - A magnetic stimulator was used for direct transcutaneous stimulation of the
      intracranial portion of the facial nerve in 30 normal subjects. Compound muscle
      action potentials (CMAPs) thus elicited in the frontal muscle of controls were of
      similar amplitude but of longer latency (1.3 +/- 0.6ms) as compare with CMAPs
      produced by conventional electrical stimulation at the stylomastoid foramen.
      Because the measured distal facial nerve motor conduction velocity was 50-60
      mm/ms, the locus of impulse generation induced by magnetic coil stimulation was
      estimated to be approximately 65mm proximal to the site of electrical stimulation
      at the stylomastoid foramen, i.e., closer to the exit of the facial nerve from
      the brain stem than to its entrance into the internal auditory meatus.

PMID- 7805161
TI  - [The relationship between the amount of gingival crevicular fluid and
      periodontitis].
AB  - In this paper, we report the results of comparing the amount of GCF, collected
      from 100 patients suffering from periodontitis and 40 patients suffering from
      gingivitis with 64 normal control subjects. The results showed that the amount of
      GCF is independent of sex and where the GCF was collected, ie., either side of
      the maxillary or mandibular teeth. However, the fluid amount was closely related
      to inflammation of the periodontium and significantly related to the severity of
      inflammation and bone destruction. This study provide evidence that the
      determination of the GCF amount is an essential criteria for detecting
      periodontal activity.

PMID- 7805162
TI  - [Studies on three-dimensional configuration of diaphragmatic lymphatics and
      absorptive mechanism of lymph from the peritoneal cavity].
AB  - Three-dimensional configuration of diaphragmatic lymphatics in five fetuses was
      studied by the lymphatic casts of scanning electron microscope and transmission
      electron microscope. A new resin, PAES-3, prepared by piperylene, acrylic ester
      and styrene was used instead of Mercox. The diaphragmatic lymphatics formed rich
      networks. There were two layers of lymphatic networks, i.e. the submesothelial
      network and the deeper network, in the muscular portion and only one layer in the
      tendinous portion of the diaphragm. The lymphatic networks were denser in the
      tendinous portion than those in the muscular portion. The lymphatic network were
      mainly composed of collecting lymphatic vessels, anastomosing side branches and
      lymphatic capillaries. The side branches often communicated the submesothelial
      network with the deeper network in the muscular portion. The collecting
      lymphatics were connected at regular intervals by way of transverse side branches
      in the tendinous portion. Numerous constrictions and notches showed the presence
      of lymphatic valves and were often found on the cast surface of the collecting
      lymphatic vessels and the side branches. The lymphatics extended as far as the
      terminal branches and can be recognized as broad, flattened and blind-ended. In
      present study, three-dimensional configuration of human diaphagmatic lymphatics
      was first described. It was suggested that the passageway of the lymph flow of
      the peritoneal cavity may be explained. From the peritoneal stomata, the lymph of
      the peritoneal cavity flowed into the channels under the peritioneum, then into
      the lymphatic lacunae and finally into the lymphatic networks under the
      diaphragmatic pleura.

PMID- 7805163
TI  - [IL-1 and TNF-alpha bioassay and PGE2 immunoassay of supernatant of cultured
      synovia in patients with rheumatic diseases].
AB  - Using arthroscopy technique, synovia were adopted and cultured, and the
      supernatant was harvested on 1, 4, 7, 14 and 28 days. The bioactivity of
      supernatant IL-1 were measured in 33 cases (RA 11 cases), TNF-alpha in 30 cases
      (RA 9 cases); the content of supernatant PGE2 were measured in 44 cases (RA 11
      cases). The results showed that IL-1 Growth Index (GI) and TNF-alpha Killing Rate
      (KR) in RA group are higher than in non-synovitis group (negative control) with
      statistically significant difference and that the cultured time of the IL-1
      highest value is consistent with TNF-alpha. In RA group, the cases treated with
      disease-modifying anti-rheumatic drugs (DMARDs), especially using the combined
      therapy, the activity of IL-1 and TNF-alpha decreased. The contents of PGE2 in
      RA+ synovitis group were higher than osteoarthritis (OA) + nonsynovitis group
      with statistically significant difference. In conclusion, cytokines such as IL-1
      and TNF-alpha have very important status in the pathogenesis of RA. This work
      provides some clues for new approaches and strategies in the treatment of RA.

PMID- 7805164
TI  - [Experimental and clinical observation on wrinkle correction by medical cosmetic
      collagen injection].
AB  - Medical cosmetic collagen is a new biomaterial for soft tissue augmentation, such
      as wrinkle correction, It consists of highly purified human collagen. The ratio
      of type I and type III collagen is 44/56. The persistence of collagen in rats is
      more than one year. Rat cells and capillaries grew into the injections.
      Fibroblasts synthesized rat collagen. Capillaries established blood supply. The
      clinical observation on 123 cases proved the safety of this product. No adverse
      reactions developing from the use of the collagen were found. It was effective in
      correcting contour deformities of the skin. More than 90% correction results were
      excellent or good.

PMID- 7805165
TI  - [Point mutation at codon 12 of c-Ki-ras oncogene in human pancreatic neoplasms
      and normal human pancreas tissue].
AB  - Point mutation at codon 12 of c-Ki-ras oncogene was tested from 2 normal human
      pancreas, 7 pancreatic endocrine neoplasms and 15 pancreatic adenocarcinomas,
      including 5 resected pancreatic adenocarcinomas, 3 cell lines of pancreatic
      adenocarcinoma and 7 nude mice transplanted tumors by dot blot and single-strand
      conformation polymorphism (SSCP) after PCR amplification, c-Ki-ras codon 12 point
      mutation was found only in pancreatic adenocarcinomas (11/15 by dot blot and
      13/15 by SSCP). No mutation was detected in normal human pancreatic tissue and
      endocrine tumors. By our experience, SSCP is more convenient and faster than dot
      blot in detecting gene mutation. Point mutation at codon 12 of c-Ki-ras oncogene
      may play an important role in the development of human pancreatic carcinoma.

PMID- 7805166
TI  - [The use of internal fixation in the treatment of spinal tuberculosis].
AB  - We have applied debridement with grafting and internal fixation techniques
      (including Luque and Dick procedures) in the treatment of tuberculosis of the
      spine in the past few years. Analysis of 18 patients showed good prognosis after
      the Luque or Dick procedure. The patients are able to walk around within a few
      days after operation. One to five years of follow-up showed no recurrence or
      kyphotic deformity.

PMID- 7805167
TI  - [Effects of (+/-) and (+) 15-methyl PGF2 alpha methyl ester on early pregnancy].
AB  - Treatment with 15-methyl PGF2 alpha methyl ester (PG05) resulted in termination
      of pregnancy and peristatic effects in mice. (+) PG05 is the active stereoisomer
      of racemic PG05. The therapeutic index of (+) PG05 was found to be closely
      similar to that of (+/-) PG05. Pregnancy of ovariectomized rats given
      progesterone and estrone was maintained normally. PG05 was shown to have no
      effect on the gestation of ovariectomized rats receiving progesterone and estrone
      injection. PG05 at a concentration of 20 micrograms/ml reduced cAMP secretion of
      rat luteal cells in response to hCG in vitro. PG05 at concentration of 10 and 20
      micrograms/ml also exerted an inhibitory effect on 8 Br-cAMP-stimulated
      progesterone production. These results suggest that in luteal cells PG05 inhibits
      steroidogenesis at the steps of gonadotropin-stimulated cAMP formation and cAMP
      induced progesterone production.

PMID- 7805168
TI  - [Increased blood pressure during hypoglycemia in patients with IDDM].
AB  - 34 patients with IDDM (17 normotensive and 17 hypertensive) were studied over a
      24 hour period by monitoring blood glucose level at 1 h frequencies during waking
      hours, ambulatory blood pressure using the accutracker and urinary free
      catecholamine by HPLC. Hypoglycemia appeared to lead to elevated blood pressure
      in 4 patients (23.5%) both normotensive and hypertensive. The average blood
      glucose levels were 2.4 +/- 0.72mmol/L and 3.3 +/- 0.62mmol/L, and the average
      blood pressure increase was 2.53 +/- 1.43/1.60 +/- 1.65 kPa and 4.66 +/-
      2.60/1.73 +/- 1.55 kPa for normotensive and hypertensive groups, respectively.
      Significant difference appeared (P < 0.05) between the two groups (normotensive
      and hypertensive). This shows that hypertensive patients with IDDM are more
      liable to have high blood pressure. This study suggested that stable blood
      glucose level is necessary for stable blood pressure for patients with IDDM.

PMID- 7805169
TI  - [Molecular cytogenetic study of Turner's syndrome with the 45, X/46,X,r(?)
      karyotype].
AB  - Two small marker chromosomes were identified as X-derived ring chromosomes by
      using the high-resolution banding technique and in situ hybridization with a
      radioactively labelled human X-chromosome-specific satellite DNA probe. This
      procedure clearly determined the origin of the marker chromosome, which had been
      impossible using conventional cytogenetic techniques. The clinical significance
      of this work is briefly discussed.

PMID- 7805170
TI  - [Microdissection of human chromosome 1].
AB  - This work began with chromosome preparation and microdissection. Booster IRS-PCR
      was developed to amplify DNA dissected form human chromosome 1. The accuracy of
      microdissection was demonstrated by chromosomal in situ suppression (CISS)
      hybridization. The amplified DNA fragments were ligated to pUC 18 vector at SmaI
      site and the average size of the inserts was about 450bp.

PMID- 7805171
TI  - [The prevention and treatment of complications with pedicle screws].
AB  - Pedicle screws are more commonly used by spinal surgeons recently. Although Roy
      Camile, Dick, Steffee, R-F etc., are all different surgical procedures, all need
      pedicle screw techniques. Up to March 1991, 61 cases with 334 screws inserted by
      Steffee and Dick operations had been performed in our hospital. Neurological
      symptoms, among all complications, are the most serious problems associated with
      these procedures. By analyzing the insertion point, transverse screw angle,
      sagittal angle and other causes of complications of pedicle screws, we present
      here our experiences for prevention and treatment of these complications.

PMID- 7805172
TI  - [Time-resolved fluoroimmunoassay of microalbuminuria].
AB  - Time-resolved fluoroimmunoassay (TrFIA) has been recognized as the most promising
      one among the so-called nonisotopic immunoassays. It is well known for its
      inherent advantages, high sensitivity, specificity and stability, rapid
      determination and wide measurement range. We have developed a new TrFIA for
      determining microalbumin in urine by using monoclonal anti-HSA (human serum
      albumin) antibody and europium label. The quality of the assay and its
      preliminary clinical application have been evaluated.

PMID- 7805173
TI  - [Significance of patellar resurfacing in total knee arthroplasty].

PMID- 7805174
TI  - Changes in folate concentration in Yoshida sarcoma after administration of
      leucovorin or cisplatin.
AB  - Both leucovorin (LV) and cisplatin (cis-dichlorodiammine platinum II, CDDP) act
      as modulators of 5-fluorouracil (5-FUra) by increasing the intracellular
      concentration of reduced folate. We measured intracellular folate levels
      following the administration of LV or cisplatin in tumor-bearing rats to
      determine the optimal schedules for their use as 5-FUra modulators. Donryu rats
      were inoculated with Yoshida sarcoma cells on the right flank. Seven days after
      tumor inoculation, the animals were injected with LV or CDDP. The kinetic and
      dose-related changes in intracellular folate concentration were analyzed by means
      of a binding assay. Folate levels in the tumor tissues were significantly higher
      than baseline 1 and 2 h after administration of LV and remained significantly
      high until 8 h after administration. Folate levels in the tumor tissues were
      significantly higher than baseline 1 and 2 h after cisplatin administration, then
      decreased to a rather low level 8 h after, and to a significantly lower level
      than baseline 24 h after administration. The folate levels in the tumor tissue
      increased in proportion to the dose of LV, but did not increase when the dose of
      cisplatin was increased from 1 mg/kg to 8 mg/kg. Repeat high-dose administration
      of LV and repeat low-dose administration of cisplatin are advocated when they are
      used as modulators of 5-FUra.

PMID- 7805175
TI  - Vinblastine and erythromycin: an unrecognized serious drug interaction.
AB  - Vinblastine and erythromycin are among the most commonly used chemotherapeutic
      and antimicrobial agents, respectively. No interaction between the two has ever
      been reported. Towards the end of a phase I study of vinblastine plus oral
      cyclosporin (to reverse multidrug resistance), three patients also received
      erythromycin to raise their cyclosporin levels. All developed severe toxicity
      consistent with a much higher vinblastine dose than was actually given. This
      apparent potentiation of vinblastine toxicity has not been previously described.

PMID- 7805176
TI  - Intracellular pharmacodynamic studies of the synergistic combination of 6
      mercaptopurine and cytosine arabinoside in human leukemia cell lines.
AB  - Selective combinations of purine and pyrimidine analogs increase remission rates
      in pediatric patients with relapsed leukemias. The combination of 6
      mercaptopurine (6-MP) and cytosine arabinoside (ara-C) may exhibit synergism
      similar to that observed for fludarabine and ara-C and may diminish the potential
      for development of resistance since the two drugs are activated by separate
      enzymatic pathways. To determine the efficacy of the combination against human
      leukemia cells, we investigated the time-concentration relationships of the drugs
      given alone or in combination to the resultant cytotoxicity. To determine whether
      the combination leads to enhanced activity of deoxycytidine kinase (dCk), the
      rate-limiting enzyme in ara-C activation, we characterized the cellular dCk in
      CCRF/CEM/0, CCRF/CEM/ara-C/7A, and CCRF/CEM/ara-C/3A monoclonal cells before and
      after treatment with 6-MP. CCRF/CEM/0 (wild type), CCRF/CEM/ara-C/7A
      (approximately 50% ara-C-resistant as determined by ara-C sensitivity assay and
      dCk characterization), and CCRF/CEM/ara-C/3A (approximately 90% resistant to ara
      C) human leukemia cells were incubated with various concentrations of 6-MP and
      ara-C given alone or in combination. Cell survival, inhibition of DNA synthetic
      capacity (DSC), ara-CTP anabolism, and dCk enzymatic characteristics were
      studied. Incubation of CEM/0 cells with 6-MP for 24 h, followed by ara-C for 48
      h, increased cell-growth inhibition by approximately 0.5-1 log10, corresponding
      to 5- to 10-fold synergism, as compared with ara-C alone after identical drug
      incubation in all cell lines. Simultaneous administration showed no synergism,
      whereas reversal of the sequence produced an antagonistic effect. The ara-CTP
      levels were 2- to 3.5-fold and 3- to 5-fold higher in CEM/0 and CEM/ara-C/7A
      cells, respectively, in cells exposed to 6-MP followed by ara-C than in those
      exposed to ara-C alone at the same concentrations. Furthermore, a progressive
      increase in ara-CTP levels was noted in CEM/0 cells exposed to increasing
      concentrations of 6-MP followed by 10 or 20 microM ara-C. A significant decrease
      in DSC was observed upon treatment of wild-type and ara-C-resistant cells with 6
      MP and ara-C. The combination of 6-MP and ara-C exhibits significant sequence
      specific synergism in both wild-type and partially ara-C-resistant leukemia cell
      lines. The combination also exerts collateral sensitivity in the ara-C-resistant
      cell lines. 6-MP pretreatment may play a role in enhancing ara-C activation, thus
      producing drug synergism in sensitive and resistant leukemia cell lines.

PMID- 7805177
TI  - In vivo screening models of cisplatin-resistant human lung cancer cell lines
      using SCID mice.
AB  - In vivo screening models of a cisplatin (CDDP)-resistant human small-cell lung
      cancer cell (SCLC) line, H69/CDDP, and a non-small-cell lung cancer cell (NSCLC)
      line, PC-14/CDDP, were evaluated. The transplantability of the tumor xenografts
      to SCID mice was more than 90%. Tumor xenografts of H69/CDDP and PC-14/CDDP
      showed CDDP resistance during in vivo treatment. The novel anticancer agent 254-S
      showed only a partial effect on the growth of H69/CDDP and PC-14/CDDP while
      ormaplatin showed no cross resistance to CDDP. The in vivo results correlated
      well with the results of the in vitro MTT assay. In this in vivo sensitivity
      test, H69/CDDP and PC-14/CDDP were more sensitive to ormaplatin than its parental
      cell lines. In vivo sensitivity testing using SCID mice bearing transplanted CDDP
      resistant tumors was shown to be useful for evaluating the effects of new anti
      cancer drugs, especially those that might overcome CDDP resistance.

PMID- 7805178
TI  - Phase I study of phosphonacetyl-L-aspartate, 5-fluorouracil, and leucovorin in
      patients with advanced cancer.
AB  - Low-dose phosphonacetyl-L-aspartate (PALA) may potentiate both 5-fluorouracil (5
      FU) incorporation into RNA and thymidylate synthase inhibition by 5
      fluorodeoxyuridylate (5-FdUMP). The gastrointestinal toxicity of 5-FU is not
      increased by PALA administration. Exogenous leucovorin, on the other hand, which
      enhances thymidylate synthase inhibition, appears to increase the clinical
      toxicity of 5-FU in a dose-dependent manner. As a result, the clinical use of
      high-dose leucovorin requires a marked dose reduction of 5-FU. Extracellular
      leucovorin levels of 1 microM suffice to maximize the enhancement of thymidylate
      synthase inhibition in several models. We conducted a trial to add leucovorin to
      the PALA/5-FU regimen. We chose a leucovorin dose that was predicted to yield end
      infusion total reduced folate concentrations of 1 microM. The major endpoint was
      to determine the maximum tolerated dose of 5-FU in this combination. The regimen
      consisted of 250 mg/m2 PALA given on day 1 and, 24 h later, escalating 5-FU doses
      ranging from 1,850 to 2,600 mg/m2 admixed with 50 mg/m2 leucovorin and given by
      24-h infusion. Courses were repeated weekly. A total of 24 patients with a median
      performance status of 1 were entered at three dose levels. Diarrhea was dose
      limiting; 6/13 patients had grade II or worse diarrhea at 2,600 mg/m2. Dose
      modification resulted in a mean dose intensity of 2,300 mg/m2 at both the 2,600-
      and 2,300-mg/m2 dose levels. The 2,300-mg/m2 dose is suitable for phase II
      testing of this regimen. Three patients (two with breast cancer and 1 with
      sarcoma) had a partial remission. We measured steady-state concentrations (Css)
      of 5-FU in 23 patients. The mean Css increased with dose from 0.738 to 1.03
      micrograms/ml. Total body clearance did not vary with dose in this range.
      Patients with grade II or worse diarrhea had a higher mean Css (1.10 +/- 0.19)
      than those with grade O or I toxicity (0.835 +/- 0.25, P < 0.02). Total bioactive
      folates (bound and free) were measured using a biological assay. Pretreatment
      values ranged from 2 to 52 nM and were not predictive of toxicity. End-infusion
      (23-h) values were somewhat lower than predicted and ranged from 400 to 950 nM.
      The risk of diarrhea was positively correlated with end-infusion total folate
      values. In a logistic regression analysis, total folate values obtained at 23 h
      were a more powerful predictor of diarrhea than were 5-FU Css values.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7805179
TI  - Daunorubicin and daunorubicinol pharmacokinetics in plasma and tissues in the
      rat.
AB  - Recent evidence suggests that 13-hydroxy metabolites of anthracyclines may
      contribute to cardiotoxicity. This study was designed to determine the
      pharmacokinetics of daunorubicin and the 13-hydroxy metabolite daunorubicinol in
      plasma and tissues, including the heart. Fisher 344 rats received 5 mg kg-1
      daunorubicin i.v. by bolus injection. Rats were killed at selected intervals for
      up to 1 week after daunorubicin administration for determination of
      concentrations of daunorubicin and daunorubicinol in the plasma, heart, liver,
      kidney, lung, and skeletal muscle. Peak concentrations of daunorubicin were
      higher than those of daunorubicinol in the plasma (133 +/- 7 versus 36 +/- 2 ng
      ml-1; P < 0.05), heart (15.2 +/- 1.4 versus 3.4 +/- 0.4 micrograms g-1; P <
      0.05), and other tissues. However, the apparent elimination half-life of
      daunorubicinol was longer than that of daunorubicin in most tissues, including
      the plasma (23.1 versus 14.5 h) and heart (38.5 versus 19.3 h). In addition,
      areas under the concentration/time curves (AUC infinity) obtained for
      daunorubicinol exceeded those found for daunorubicin in almost all tissues, with
      the ratios being 1.9 in plasma and 1.7 in the heart. The ratio of daunorubicinol
      to daunorubicin concentrations increased dramatically with time from < 1 at up to
      1 h to 87 at 168 h in cardiac tissue. Thus, following daunorubicin injection,
      cumulative exposure (AUC infinity) to daunorubicinol was greater than that to
      daunorubicin in the plasma and heart. If daunorubicinol has equivalent or greater
      potency than daunorubicin in causing impairment of myocardial function, it may
      make an important contribution to the pathogenesis of cardiotoxicity.

PMID- 7805180
TI  - Phase I and pharmacology study of flavone acetic acid administered two or three
      times weekly without alkalinization.
AB  - Flavone acetic acid (FAA, NSC 347512) is a synthetic flavonoid compound with a
      unique form of preclinical antitumor activity, but its mechanism of action is
      still not known. In an attempt to exploit the remarkable preclinical activity of
      this compound in such a way as to allow its use as a clinically useful agent, we
      performed a phase I and pharmacology study with frequent administration and no
      hyperhydration or alkalinization. Sixteen patients (9 men, 7 women) were given
      FAA as 6-h i.v. infusions 2 or 3 times a week (10 and 6 patients, respectively),
      at doses ranging from 2.5 to 8.1 g/m2. A total of 130 doses were administered
      during this study. Sedation, arterial hypotension, vomiting and diarrhea were the
      predominant toxicities observed at the highest dose (8.1 g/m2. One patient
      developed severe but reversible multiple organ failure. No treatment-related
      deaths occurred. Pharmacokinetics was linear for the doses studied, with peak
      plasma levels ranging from 39 to 449 micrograms/ml and a mean terminal half-life
      of 3.1 h. No drug accumulation was observed with this frequent-administration
      schedule. No objective response was observed. Three FAA infusions per week at 8.1
      g/m2 could be recommended as an optimal and tolerable schedule.

PMID- 7805181
TI  - Treatment of advanced hormone-refractory prostate carcinoma with a combination of
      etoposide, pirarubicin and cisplatin.
AB  - A total of 20 patients with hormone-refractory prostate carcinoma entered a pilot
      study of combination chemotherapy based on the EAP (etoposide, Adriamycin and
      cisplatin) regimen, in which Adriamycin was replaced by pirarubicin, a less
      cardiotoxic derivative of Adriamycin. The response was assessed by criteria
      modified from those of the National Prostatic Cancer Project: prostate-specific
      antigen was employed instead of acid phosphatase. Of 18 evaluable patients, 6
      achieved a partial response, 5 had stable disease, and in 7 the disease had
      progressed during therapy; thus, the overall response rate was 33.3% [95%
      confidence interval (CI) 11.5-55.1%]. Significant pain alleviation and
      performance status improvement were obtained in 5 of 12 patients (41.7%; CI 13.8
      69.6%) and 3 of 13 patients (23.1%; CI 0.2-46.0%), respectively. Although
      myelosuppression was moderate to severe, no chemotherapy-related deaths or
      bacteriologically documented sepsis occurred; nor was there any clinical
      cardiotoxicity. All the responding patients received maintenance chemotherapy
      with etoposide thereafter. At present, the median duration of response is 33
      weeks (range: 23-91 weeks) and the median survival period for all patients is 42
      weeks (range: 27(+)-136 weeks), with 12 deaths. In spite of the small number of
      patients treated, these results suggest that this chemotherapy regimen is active
      in advanced hormone-refractory prostate carcinoma.

PMID- 7805182
TI  - Contrasting influence of peplomycin and azelastine hydrochloride (Azeptin) on
      reactive oxygen generation in polymorphonuclear leukocytes, cytokine generation
      in lymphocytes, and collagen synthesis in fibroblasts.
AB  - The influence of peplomycin (PLM) and azelastine hydrochloride (Azeptin) on
      reactive oxygen (RO) and cytokine generation was examined in human peripheral
      blood mononuclear leukocytes, polymorphonuclear leukocytes (PMN), and rabbit
      alveolar macrophages (RAM). In addition, the influence of these drugs on DNA and
      collagen synthesis was investigated in human gingival and rabbit pulmonary
      fibroblasts. In vitro, PLM increased the FMLP- and PMA-induced chemiluminescence
      and superoxide (O2-) generation in human PMN and RAM in a dose-dependent manner.
      In contrast to PLM, Azeptin dose-dependently suppressed RO generation. Such
      contrasting actions of PLM and Azeptin were also observed in RAM and PMN obtained
      from rabbits treated with PLM or Azeptin. Even when human PMN were preincubated
      with 10-100 micrograms/ml of PLM, the increase in RO generation was negligible in
      the presence of 10(-5) M Azeptin in the culture medium. No increases in RO
      generation were observed in RAM or PMN obtained from rabbits that had received
      PLM (0.1 mg/kg per day) and Azeptin (0.04 mg/kg per day) concomitantly. PLM
      suppressed superoxide dismutase activity in RAM and human PMN, while Azeptin did
      not affect this activity. In vitro, PLM up-regulated the release of interleukin-1
      beta, interleukin-6, tumor necrosis factor alpha, and granulocyte-macrophage
      colony-stimulating factor both from human cells and from RAM and pulmonary
      fibroblasts. In the generation of these cytokines, Azeptin abrogated the up
      regulatory action of PLM. PLM and Azeptin also had contrasting actions in
      [3H]thymidine and [3H]proline incorporation in human and rabbit fibroblasts.
      Furthermore, protein tyrosine phosphorylation, in particular that of a 115-kDa
      protein in human PMN, was suppressed by Azeptin and enhanced by PLM. These
      results seem to indicate that up-regulated RO and collagen generation are the
      causative factors of PLM-induced pulmonary fibrosis and that Azeptin may suppress
      the adverse effect.

PMID- 7805184
TI  - Phase I study of RP 49532A, a new protein-synthesis inhibitor, in patients with
      advanced refractory solid tumors.
AB  - Giroline (RP 49532A) is a new protein-synthesis inhibitor with broad antitumor
      activity in experimental models. In the present phase I study, Giroline was given
      by 24-h i.v. infusion every 3 weeks at doses ranging from 3 to 15 mg/m2 to 12
      patients with advanced refractory solid tumors. The dose-limiting toxic effects
      were delayed hypotension and severe asthenia. The maximum tolerated dose (MTD)
      was 15 mg/m2. Transient nausea and vomiting during infusion were reported at all
      dose levels. Mild reversible prolongation of prothrombin time and activated
      partial thromboplastin time was observed in most patients at dose levels above 3
      mg/m2. No antitumor activity was observed. The toxicity profile of Giroline
      precludes further evaluation in cancer patients.

PMID- 7805183
TI  - Pharmacokinetics and pharmacodynamics of topotecan administered daily for 5 days
      every 3 weeks.
AB  - Topotecan is a novel semisynthetic derivative of the anticancer agent
      camptothecin and inhibits the intranuclear enzyme topoisomerase I. The lactone
      structure of topotecan, which is in equilibrium with the inactive ring-opened
      hydroxy acid, is essential for this activity. The open form predominates at
      physiological pH. We performed a pharmacokinetic study as part of a phase I study
      in patients with various types of solid tumors, where topotecan was administered
      in a 30-min infusion daily on 5 consecutive days every 3 weeks. The plasma
      kinetics of topotecan could be described best using an open two-compartment model
      with t1/2(alpha) and t1/2(beta) of 8.1 (range 0.3 to 40.7) min and 132 (range 49
      to 286) min, respectively. The plasma concentration-time profiles of the
      metabolite, however, could be described using a one-compartment model with
      t1/2(formation) of 29.0 (range 5.6-99.5) min and t1/2 (elimination of 123.2
      (range 32-265) min, respectively. The lactone was the predominate form during the
      first hour from the start of infusion, but was rapidly converted into its ring
      opened structure. The elimination rate of topotecan was independent of the dose.
      There were linear relationships between the dose (mg m-2 day-1), the area under
      the plasma concentration versus time curve (AUC) of topotecan and its metabolite,
      the total AUC, peak plasma lactone concentrations, and the time period that the
      topotecan concentrations remained above 10 nM. Different models were used to
      correlate pharmacokinetic and pharmacodynamic parameters. The percentage decrease
      in absolute neutrophil count (ANC) was related to these parameters and plots were
      well fitted by linear and sigmoidal Emax models.

PMID- 7805185
TI  - Effects of storage on the binding of carboplatin to plasma proteins.
AB  - Plasma ultrafiltrates are routinely used in pharmacokinetic studies of
      carboplatin. Experiments were performed to detect and quantitate artifactual
      decreases in the platinum concentration of ultrafiltrates prepared from plasma
      samples stored at -20 degrees C and -70 degrees C. Carboplatin was added to
      anticoagulated, whole human blood to produce a 20 microgram/ml concentration.
      Plasma produced from the blood was stored frozen at either -20 degrees C or -70
      degrees C. Aliquots from each storage condition were thawed and ultrafiltered
      once a week for up to 100 days. Platinum concentrations in ultrafiltrates and
      plasma were determined by flameless atomic absorption spectrometry. There was no
      loss of ultrafilterable platinum in plasma samples stored at -70 degrees C,
      whereas there was a steady decrease in free platinum concentration in
      ultrafiltrates prepared from plasma samples stored at -20 degrees C. These
      results imply that pharmacokinetic studies of carboplatin should use
      ultrafiltrates prepared immediately or that plasma for such studies should be
      stored at -70 degrees C. Storage of carboplatin-containing plasma at -20 degrees
      C and subsequent ultrafiltration is not acceptable, because measurement of
      platinum in such ultrafiltrates will be artifactually low.

PMID- 7805186
TI  - Evaluation of anthracycline cardiotoxicity with the model of isolated, perfused
      rat heart: comparison of new analogues versus doxorubicin.
AB  - We have compared the cardiotoxicity of 3 anthracyclines in a model of isolated
      perfused rat heart using the Langendorff technique. The contractile state and
      ventricular compliance were studied. Doxorubicin, epirubicin and pirarubicin were
      perfused at concentrations of 10(-6) and 10(-5) M during 70 min. The cardiac
      accumulation of the drugs was studied by HPLC. No significant alteration of
      cardiac functional parameters was observed at 10(-6) M. At 10(-5) M, epirubicin
      produced a significantly greater alteration of cardiac contractility than
      doxorubicin, whereas pirarubicin exerted first an inotropic effect followed by a
      recovery to initial values at the 60th min. Anthracycline accumulation in the
      heart was dose-dependent; epirubicin accumulated to a 30% greater extent than
      doxorubicin and pirarubicin heart concentrations were 4-5 times higher than those
      of doxorubicin at the end of the perfusion. These results suggest that
      doxorubicin and epirubicin have the same intrinsic cardiac toxicity, and that
      their distinct clinical cardiotoxicity must be explained by pharmacokinetic
      differences, whereas pirarubicin is much less cardiotoxic than the other
      anthracyclines because of different pharmacodynamic properties.

PMID- 7805187
TI  - Inhibition of O6-alkylguanine-DNA alkyltransferase in animal and human ovarian
      tumor cell lines by O6-benzylguanine and sensitization to BCNU.
AB  - O6-Alkylguanine-DNA alkyltransferase (O6-AGT) activity in rat ovarian tumor lines
      O-342 and O 342/DDP was 103.4 +/- 18.4 and 240.9 +/- 40.2 fmol/mg protein,
      respectively; thus, cisplatin (DDP) resistance was paralleled by an increase in
      O6-AGT activity by a factor of approximately 2.3. The DDP-resistant line
      expressed a collateral resistance to BCNU. Both lines could be sensitized to BCNU
      by O6-BG, with sensitization factors of 6.0 and 2.1, respectively. In neither
      line did depletion of O6-AGT have any sensitizing effect towards DDP. In the
      human ovarian cancer lines SK-OV-3 and OAW 42, O6-AGT activity was 337.6 +/- 18.2
      and 180.0 +/- 39.9 fmol/mg protein, respectively; in these lines depletion of O6
      AGT activity by O6-BG treatment resulted in sensitization factors of 3.0 and 4.1,
      respectively. The increase in sensitivity of ovarian tumor cell lines against a
      chloroethylating agent by O6-AGT depletion and possible pharmacological
      advantages of regional (i.p.) administration of this combination might be
      beneficial in advanced ovarian cancer.

PMID- 7805189
TI  - Task force on research in cardiopulmonary dysfunction in critical care medicine.

PMID- 7805188
TI  - The structure of P-glycoprotein and the secretion of lysosomal enzymes in
      multidrug-resistant cells.
AB  - We have previously demonstrated that multidrug-resistant cells have a lower
      content of lysosomal enzymes, a consequence of an increased rate of secretion.
      The question was therefore to know whether an intact functional P-glycoprotein
      was necessary for expression of this property. Control NIH3T3 and mdr1-gene
      transfected cells (pHaMDR1) were used together with 2 variants either lacking 23
      amino acids at the carboxyl terminal (pHaMDRC 23) or in which 4 extra amino acids
      are inserted (pHaMDRBL2). Transfected and variant cells exhibited reduced uptake
      of [3H]-vinblastine and [3H]-daunomycin, a finding consistent with their drug
      resistance. By contrast, only pHaMDR1 cells had a reduced level of N-acetyl
      glucosaminidase that paralleled an increased rate of secretion of the same
      enzyme. The mutant cells secreted lysosomal enzyme at the same rate and had the
      same intracellular lysosomal enzyme content as NIH3T3 cells. Abnormal behavior of
      lysosomal enzymes in multidrug-resistant cells therefore seemed to require an
      intact P-glycoprotein molecule. Although sequestration in lysosomes and then
      secretion of drugs may possibly contribute to protection, it would not be an
      essential component of multidrug resistance.

PMID- 7805190
TI  - Probucol protects against adriamycin cardiomyopathy without interfering with its
      antitumor effect.
AB  - BACKGROUND: The usefulness of adriamycin (ADR), a potent antitumor antibiotic, is
      limited by the development of life-threatening cardiomyopathy and congestive
      heart failure. Subcellular changes leading to heart failure are suggested to be
      mediated by a drug-induced increase in free radicals and lipid peroxidation. In
      an earlier study, concurrent treatment with probucol (PROB), a lipid-lowering
      drug with strong antioxidant properties, was shown to offer only partial
      protection against ADR cardiomyopathy. The present study had two aims: to
      determine whether this protective effect can be improved further by extended
      treatment with PROB, and to determine whether PROB affects the antitumor
      properties of ADR. METHODS AND RESULTS: ADR (cumulative dose, 15 mg/kg body wt)
      was administered in rats in six equal injections (IP) over a period of 2 weeks.
      Three weeks after the end treatment, cardiomyopathy and congestive heart failure
      were characterized by ascites, congested liver, depressed cardiac function,
      elevated left ventricular end-diastolic pressure, and myocardial cell damage.
      Myocardial glutathione peroxidase (GSHPx) activity was decreased and lipid
      peroxidation was increased. Administration of PROB (cumulative dose, 120 mg/kg
      body wt) in 12 equal injections (IP), before and concurrent with ADR, completely
      prevented these cardiomyopathic changes, normalized left ventricular function,
      lowered mortality, and eliminated ascites. Treatment with PROB was also
      accompanied by an increase in myocardial GSHPx and superoxide dismutase
      activities with a concomitant decrease in lipid peroxidation. Tumor regression in
      syngeneic DBA/2 mice inoculated with L5178Y-F9 lymphoma cells in the ADR+PROB
      group was significant and comparable to the ADR group. CONCLUSIONS: These data
      show for the first time that PROB can provide complete protection against ADR
      cardiomyopathy without interfering with antitumor properties of the drug. This
      protective effect of PROB may be related to the maintenance of the antioxidant
      status of the heart.

PMID- 7805191
TI  - Transesophageal echocardiography for the diagnosis and management of
      nonobstructive thrombosis of mechanical mitral valve prosthesis.
AB  - BACKGROUND: Diagnosis of a mechanical mitral valve prosthesis thrombosis is
      currently made with transthoracic Doppler echocardiography and occasionally with
      fluoroscopy. However, identifying a thrombus on a valve prosthesis may be
      difficult, especially if the thrombus is nonobstructive. To prospectively define
      the role of transesophageal echocardiography for identification of nonobstructive
      thrombi, we studied a series of patients in whom the prosthetic valve was
      considered to function normally on clinical examination and transthoracic
      echocardiography. METHODS AND RESULTS: One hundred fourteen consecutive patients
      with mechanical mitral valve prosthesis were investigated by both transthoracic
      echocardiography and transesophageal echocardiography. These examinations were
      performed for recent systemic emboli (15 patients), fever of unknown etiology (11
      patients), routine postoperative evaluation (56 patients), and other reasons (32
      patients). Based on transthoracic echo diagnosis, all prostheses were considered
      normal. Yet, in 20 patients transesophageal echocardiography revealed the
      presence of a 2- to 15-mm-long mobile thrombus localized on the atrial surface of
      the prosthesis. When compared with the remaining 94 patients with no visible
      thrombi, there was no significant difference between the two groups in terms of
      incidence of atrial fibrillation (65% versus 52%), left atrial size (48 +/- 9
      versus 51 +/- 13 mm), left ventricular end-diastolic diameter (49 +/- 10 versus
      51 +/- 13 mm) and fractional shortening (28 +/- 9% versus 31 +/- 10%), presence
      of spontaneous contrast to the left atrium (40% versus 41%), transprosthetic mean
      pressure gradient (4.0 +/- 1.4 versus 3.9 +/- 1.5 mm Hg), or the type of
      prosthesis used. After we discovered a nonobstructive thrombosis, patients were
      treated with heparin (n = 9) or oral anticoagulation (n = 11). The presence of a
      localized thrombus was confirmed in 3 patients who were operated on. In the
      present study, evolution appeared to depend on thrombus size: of 14 patients
      exhibiting a small (< 5 mm) thrombus, 10 had an uneventful course, whereas 5 of 6
      patients with a large (> or = 5 mm) thrombus developed complications or died.
      CONCLUSIONS: Transesophageal echocardiography appears to be a reliable method to
      diagnose thrombi on a mechanical mitral valve prosthesis, even when transthoracic
      Doppler echocardiographic parameters appear to be normal. Transesophageal echo
      assessment of thrombus size may be helpful in deciding whether a patient with
      mitral prosthesis should be treated by anticoagulation, thrombolysis, or valve
      rereplacement.

PMID- 7805192
TI  - Formation of the tricuspid valve in the human heart.
AB  - BACKGROUND: Some of the problems concerning the origin of the inlet component of
      the definitive right ventricle were resolved in a previous study in which we
      showed it to be derived exclusively from the embryonic right ventricle. Questions
      remain, however, concerning the relative contributions of endocardial cushion
      tissue and myocardium to the definitive valvar apparatus guarding the right
      atrioventricular orifice and the origin of the valvar leaflets. METHODS AND
      RESULTS: The formation of the tricuspid valve was studied by scanning electron
      microscopic and immunohistochemical techniques. Concurrent with the development
      of the right atrioventricular connection, a myocardial ridge forms at the
      boundary between the atrioventricular canal and the embryonic right ventricle. It
      grows to become a myocardial gully that funnels atrial blood beneath the lesser
      curvature of the initial heart tube toward the middle of the right ventricle.
      Fenestrations in the floor of the gully create an additional inferior opening in
      the funnel, transforming its initial anterior rim into the septomarginal
      trabeculation. The septum formed by the fusion of the endocardial ridges of the
      outflow tract becomes myocardialized in its inferior portion to form, in part,
      the outlet septum and, in part, the supraventricular crest. The smooth atrial
      surface of the tricuspid valvar leaflets develops from endocardial cushion
      tissue. The leaflets become freely movable, however, only after delamination of
      the tension apparatus within the myocardium. The inferior and septal leaflets
      derive from the gully and the ventricular septum, their delamination being a
      single, continuous process. The antero-superior leaflet forms by delamination
      from the developing supraventricular crest. CONCLUSIONS: The leaflets of the
      tricuspid valve develop equally from the endocardial cushion tissues and the
      myocardium. The myocardium contributing to the valve comes from two sources, the
      tricuspid gully complex and the developing supraventricular crest. These findings
      facilitate the understanding of several congenital malformations.

PMID- 7805193
TI  - Feasibility of exercise stress echocardiography for the follow-up of children
      with coronary involvement secondary to Kawasaki disease.
AB  - BACKGROUND: The development of coronary aneurysms as sequelae of Kawasaki disease
      can result in myocardial ischemia, infarction, and sudden death. Traditionally,
      these patients have undergone coronary angiography and nuclear stress imaging for
      risk stratification and follow-up. However, angiography is invasive, and both
      modalities expose the patient to repeated radiation, which is an important issue
      in children. The purpose of this study was to determine the feasibility of
      performing exercise stress echocardiography in children diagnosed with coronary
      abnormalities secondary to Kawasaki disease. METHODS AND RESULTS: Treadmill
      exercise stress echocardiographic studies were performed in 28 children ages 6 to
      16 years. All had acute Kawasaki disease 1 to 10 years before study, and coronary
      artery abnormalities were identified during previous echocardiographic imaging.
      Patients were exercised using a standard Bruce protocol. Transthoracic
      echocardiographic images, obtained in the parasternal long, short, apical two-
      and four-chamber views immediately before and after exercise, were digitized for
      review and analysis. In baseline studies before exercise, wall motion
      abnormalities were identified in 2 patients; these segments became normal with
      exercise. Two patients developed new exercise-induced wall motion abnormalities
      that corresponded to angiographically defined critical stenosis of the left
      anterior descending coronary artery. No patients had resting or exercise-induced
      ECG evidence of ischemia. There were no adverse reactions, and 26 of 28 patients
      had normal exercise tolerance. CONCLUSIONS: Among patients with coronary artery
      involvement resulting from Kawasaki disease, exercise stress echocardiography is
      a safe, noninvasive procedure and may identify children with myocardial ischemia
      that was not detected with ECG stress test alone.

PMID- 7805194
TI  - Assessment of fetal compromise by Doppler ultrasound investigation of the fetal
      circulation. Arterial, intracardiac, and venous blood flow velocity studies.
AB  - BACKGROUND: Doppler studies of the fetal circulation in intrauterine growth
      retardation and hypoxia have demonstrated a compensatory redistribution of
      arterial blood flow with increased flow to the cerebrum and myocardium and
      decreased flow to the periphery. The aim of this study was to evaluate the
      significance of changes in fetal venous blood flow waveforms in high-risk
      pregnancies and to investigate the time relation between alterations in venous
      and arterial Doppler waveform indices in compromised fetuses. METHODS AND
      RESULTS: The cross-sectional study consisted of 108 high-risk singleton
      pregnancies between 23 and 42 weeks' gestation without fetal chromosomal
      abnormalities or major malformations. Blood flow velocity waveforms were recorded
      from the umbilical arteries, descending thoracic aorta, middle cerebral artery,
      tricuspid and mitral ventricular inflow, ductus venosus, inferior vena cava, and
      the right hepatic vein. The mean velocity and pulsatility index were calculated
      for arterial vessels, the E/A ratio for atrioventricular blood flow, and peak
      forward velocities during ventricular systole and early diastole, the lowest
      forward velocity or peak reverse velocity during arterial contraction, and time
      averaged maximum velocity for venous vessels. Two ratios for venous waveforms,
      one of which is the equivalent of the pulsatility index, were calculated. Fetal
      biophysical assessment was based on a computerized cardiotocogram and the
      biophysical profile score. The compromised group consisted of 37 fetuses
      delivered by cesarean section for an abnormal heart rate trace (n = 21) or severe
      preeclampsia (n = 9) or which died in utero (n = 7) within 10 days of their last
      Doppler investigation. This group showed significant alterations in arterial and
      venous flow velocity waveforms but not in atrioventricular inflow. Additionally,
      to find out whether venous Doppler investigation may help to detect a worsening
      of the situation in fetuses already showing arterial blood flow redistribution,
      we analyzed the data of these fetuses separately. The 41 fetuses that had an
      aorta/middle cerebral artery pulsatility index ratio > 95th percentile were
      divided into compromised and non-compromised groups according to their
      biophysical assessment and whether or not they developed fetal distress (cesarean
      section for abnormal heart rate trace or intrauterine death). The mean values for
      Doppler parameters of the compromised groups differed significantly from the
      noncompromised groups in all venous vessels, whereas differences on the arterial
      side were much less pronounced. Velocity ratios of venous waveforms were
      significantly higher, and absent or reverse flow in the ductus venosus with
      atrial contraction indicated a poor prognosis, with a perinatal mortality of 5
      out of 8. CONCLUSIONS: Fetal compromise is associated with significant
      alterations in the fetal arterial and venous circulation. Significant changes in
      venous Doppler waveforms develop due to increased afterload and perhaps
      myocardial failure in late deterioration after fetal arterial redistribution is
      established and seem to be closely related to abnormal biophysical assessment
      findings. Therefore, Doppler investigation of the fetal venous circulation may
      play an important role in monitoring the redistributing growth retarded fetus and
      thereby may help to determine the optimal time for delivery.

PMID- 7805195
TI  - Effects of chronic systemic administration of basic fibroblast growth factor on
      collateral development in the canine heart.
AB  - BACKGROUND: Recently we reported that intracoronary administration of basic
      fibroblast growth factor (bFGF), a potent angiogenic peptide, increases
      collateral blood flow in dogs subjected to progressive left circumflex coronary
      artery (LCx) occlusion. The aim of the present study was to examine the effect of
      systemically administered bFGF on collateral blood flow and to assess its
      pharmacokinetics and potential side effects. METHODS AND RESULTS: Forty-seven
      dogs were subjected to progressive ameroid-induced occlusion of the LCx, an
      intervention known to induce the development of collateral vessels. In phase I of
      the investigation, dogs were randomized to receive bFGF 1.74 mg/d (n = 10) or
      saline (n = 9) as a left atrial injection for 4 weeks. Relative collateral blood
      flow was assessed serially with radiolabeled microspheres in the conscious state
      during maximal coronary vasodilatation. Initiation of bFGF treatment was
      temporally associated with a marked acceleration of collateral development;
      however, collateral flow in control dogs improved toward the end of the study,
      approaching that of bFGF-treated dogs at the 38-day end point. Phase II of the
      investigation was a three-armed study of extended duration to determine whether
      bFGF caused a sustained increase in collateral function. Dogs were randomized to
      receive bFGF 1.74 mg/d for 9 weeks (n = 7), bFGF 1.74 mg/d for 5 weeks followed
      by placebo for 4 weeks (n = 11), or placebo for 9 weeks (n = 10). Relative and
      absolute collateral blood flow were assessed serially with microspheres during
      maximal coronary vasodilatation. Between the 10th and 17th days after ameroid
      placement, bFGF-treated dogs exhibited marked improvement in collateral flow such
      that maximal collateral conductance exceeded that of controls by 24% at the 5
      week crossover point. Final collateral conductance was similar in dogs receiving
      bFGF for 5 and 9 weeks despite withdrawal of treatment in the former group. bFGF
      administration was associated with a 21% increase in final collateral conductance
      as well as a 49% increase in collateral zone vascular density. Prolonged bFGF
      administration was also associated with a decrease in arterial pressure, moderate
      thrombocytopenia, and moderate, reversible anemia. CONCLUSIONS: Systemic
      administration of bFGF enhanced collateral conductance in dogs with progressive
      single-vessel coronary occlusion. The beneficial effect of bFGF occurred
      primarily between the 7th and 14th days of therapy, and regression of collateral
      development was not noted after withdrawal of treatment. The present
      investigation provides impetus to the concept that collateral development can be
      enhanced pharmacologically-specifically by bFGF-raising the possibility that such
      an intervention might eventually be applied clinically.

PMID- 7805196
TI  - Acoustic propagation properties of normal, stunned, and infarcted myocardium.
      Morphological and biochemical determinants.
AB  - BACKGROUND: Identification of viable but stunned myocardium remains a major
      problem. Since stunned myocardium results in impairment of myocardial function
      without any structural damage and infarcted myocardium causes major structural
      disruption, we postulated that acoustic properties could distinguish between the
      two insults. METHODS AND RESULTS: Anesthetized open-chest dogs underwent a total
      occlusion of the left anterior descending coronary artery for 15 minutes
      (stunned, n = 7) and 90 minutes (infarcted, n = 8), followed by reperfusion for 3
      hours. Circumflex coronary artery perfusion territory (n = 15) served as normal
      control tissue. Regions of myocardium were quantitatively evaluated with a
      scanning laser acoustic microscope operating at 100 MHz and a research ultrasound
      system operating at 4 to 7 MHz. Four ultrasonic parameters were determined:
      attenuation coefficient (an index of loss per unit distance), speed of
      propagation, a spatial variation of propagation speed called the heterogeneity
      index (HI), and ultrasonic backscatter at 5 MHz (IBR5). Myocardial water, lipid,
      and protein contents of normal, stunned, and infarcted myocardium were also
      determined. The attenuation coefficient of normal myocardium (179 +/- 20 dB/cm)
      was significantly greater than that of stunned (136 +/- 7 dB/cm, P < .001) and
      infarcted (130 +/- 8 dB/cm, P < .001) myocardium. The propagation speed of normal
      myocardium (1597 +/- 6 m/s) was similar to that of stunned (1600 +/- 6 m/s) and
      significantly higher than that of infarcted (1575 +/- 7 m/s, P < .001)
      myocardium. The HI for specimen thicknesses of 75 to 100 microns showed an
      increase of 33% between normal (5.0 +/- 0.8 m/s) and stunned (7.5 +/- 2.3 m/s, P
      < .05) myocardium. However, for the infarcted myocardium (5.8 +/- 2.0 m/s), the
      HI was essentially the same as that of the normal myocardium (5.0 +/- 0.8 m/s).
      The IBR5 of normal (-47.1 +/- 1.0 dB) was not significantly different from that
      of stunned myocardium (-46.8 +/- 0.9 dB). The IBR5 of infarcted myocardium (-42.4
      +/- 1.0 dB) was significantly greater than that of normal myocardium. Myocardial
      water and protein contents were similar in the normal and stunned myocardium.
      Water content in the infarcted myocardium (80.8 +/- 2%) was significantly greater
      (P < .05) than in the normal (72.7 +/- 1.3%), and protein content of 18.5 +/-
      0.7% was significantly lower (P < .05) than the normal (21.4 +/- 0.8%). Lipid
      content was increased in the stunned (8.5 +/- 0.5%) and virtually absent in the
      infarcted myocardium (0.8 +/- 0.3%) compared with normal (5.5 +/- 0.6%).
      CONCLUSIONS: We conclude that acoustic propagation properties can identify
      stunned and infarcted myocardium and may be related to biochemical/morphological
      differences.

PMID- 7805197
TI  - Relevance of blockade of cardiac and circulatory angiotensin-converting enzyme
      for the prevention of volume overload-induced cardiac hypertrophy.
AB  - BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors show major differences
      in their affinity for cardiac and other tissue ACEs, and their effects on tissue
      ACE range from minimal to nearly complete blockade. Angiotensin II taken up from
      the circulation or generated in the heart may mediate the cardiac hypertrophic
      response to increased cardiac load. Thus, differences between the ACE inhibitors
      regarding their effects on cardiac ACE may determine their effects on prevention
      or regression of cardiac hypertrophy. METHODS AND RESULTS: In the present study,
      we assessed the effects of ACE inhibitors with low (enalapril) and high
      (quinapril) affinity for cardiac tissue ACE on prevention of volume overload
      induced cardiac hypertrophy in relation to their hemodynamic effects. Both
      blockers were equipotent for circulatory ACE as assessed from the pressure
      response curve to angiotensin I. Both blockers partially (and similarly)
      prevented the increase in left ventricular end-diastolic pressure by aortocaval
      shunt. However, only quinapril prevented or attenuated the development of right
      ventricular hypertrophy and left ventricular hypertrophy and dilation.
      CONCLUSIONS: The present findings further stress the involvement of the renin
      angiotensin system as a trophic stimulus in the development of cardiac
      hypertrophy in this model. Moreover, the low affinity of enalapril for cardiac
      ACE appears to lead to continuous angiotensin II generation in the heart and can
      thus explain the failure of enalapril to attenuate hypertrophic response of the
      heart induced by shunt despite decreasing cardiac volume overload.

PMID- 7805198
TI  - Myocardial fibrosis and stiffness with hypertrophy and heart failure in the
      spontaneously hypertensive rat.
AB  - BACKGROUND: Fibrosis is commonly found in association with cardiac hypertrophy
      and failure, but the relation of the connective tissue response to the
      development of impaired cardiac function remains unclear. We examined passive
      myocardial stiffness, active contractile function, and fibrosis in the
      spontaneously hypertensive rat (SHR), a model of chronic pressure overload in
      which impaired cardiac function follows a long period of stable hypertrophy.
      METHODS AND RESULTS: We studied the passive and active mechanical properties of
      left ventricular (LV) papillary muscles isolated from normotensive Wistar-Kyoto
      (WKY) rats and spontaneously hypertensive rats (SHR) at the ages of 12 months and
      20 to 23 months. Seven of 15 SHR between 20 and 23 months of age had findings
      consistent with heart failure (SHR-F). In comparison to preparations from WKY
      rats and nonfailing SHR (SHR-NF), papillary muscles from the SHR-F group
      demonstrated increased passive stiffness (central segment exponential stiffness
      constant, kcs: SHR-F 95.6 +/- 19.8, SHR-NF 42.1 +/- 9.7, WKY rats 39.5 +/- 9.5
      (mean +/- SD); SHR-F P < .01 versus SHR-NF, WKY rats). The increase in stiffness
      was associated with an increase in LV collagen concentration (SHR-F 8.71 +/-
      3.14, SHR-NF 5.83 +/- 1.20, WKY rats 4.78 +/- 0.70 mg hydroxyproline/g dry LV wt;
      SHR-F P < .01 versus SHR-NF, WKY rats); an increase in interstitial fibrosis, as
      determined histologically (SHR-F 13.5 +/- 8.0%, SHR-NF 4.9 +/- 2.1%, WKY rats 3.6
      +/- 0.8%; SHR-F P < .01 versus SHR-NF, WKY rats); and impaired tension
      development (SHR-F 3.18 +/- 1.27, SHR-NF 4.41 +/- 1.04, WKY rats 4.64 +/- 0.85
      kdyne/mm2; SHR-F P < .05 versus SHR-NF; P < .01 versus WKY rats). CONCLUSIONS:
      The development of heart failure in the aging SHR is associated with marked
      myocardial fibrosis, increased passive stiffness, and impaired contractile
      function relative to age-matched nonfailing SHR and nonhypertensive control
      animals. These data suggest that fibrosis or events underlying the connective
      tissue response are important in the transition from compensated hypertrophy to
      failure in the SHR.

PMID- 7805199
TI  - Relation of ultrasonic backscatter and acoustic propagation properties to
      myofibrillar length and myocardial thickness.
AB  - BACKGROUND: Ultrasonic backscatter demonstrates a cardiac cycle-dependent
      modulation. The exact mechanism of the modulation is under debate. The objective
      of the present study was to test the hypothesis that a change in size and
      configuration of myofilaments from systole to diastole alters acoustic
      propagation properties and backscatter. METHODS AND RESULTS: In vivo measurements
      were made of integrated backscatter at 5 MHz (IBR5), followed by in vitro
      measurements of ultrasonic attenuation, speed, and heterogeneity index using a
      scanning laser acoustic microscope at 100 MHz. Studies were performed in canine
      hearts (16) arrested in systole (8) with calcium chloride or arrested in diastole
      (8) with potassium chloride. Sarcomere length was measured with a calibrated
      eyepiece on a Ziess microscope. Wall thickness was measured with calipers. The
      attenuation coefficient of 220 +/- 34 dB/cm during systole was significantly
      higher than the coefficient of 189 +/- 24 dB/cm during diastole (P < .01); the
      IBR5 of -44.7 +/- 1.2 dB during systole was significantly greater than the IBR5
      of -47.0 +/- 1.0 dB during diastole (P < .01); the ultrasonic speed of 1591 +/-
      11 m/s during systole was higher than the speed of 1575 +/- 4.2 m/s during
      diastole (P < .01); and the heterogeneity index of 7.4 +/- 1.8 m/s during systole
      was significantly lower than the index of 9.0 +/- 2.0 m/s during diastole (P <
      .02). The sarcomere length of 1.804 +/- 0.142 microns during diastole was
      significantly higher than the length of 1.075 +/- 0.177 micron during systole (P
      < .01). Wall thickness was significantly greater during systole than during
      diastole (20 +/- 3 versus 9 +/- 3 mm, P < .01). CONCLUSIONS: Ultrasonic
      backscatter and propagation properties are directly related to sarcomere length
      and myocardial thickness and may be responsible for cardiac cycle-dependent
      variation in backscatter.

PMID- 7805200
TI  - Effect of tachycardia heart failure on the restitution of left ventricular
      function in closed-chest dogs.
AB  - BACKGROUND: Cardiac mechanical restitution and relaxation restitution are thought
      to be physiological correlates of the recovery kinetics of Ca2+ release
      mechanisms and sequestration capacity of the sarcoplasmic reticulum (SR). Since
      congestive heart failure is characterized by abnormal intracellular Ca2+
      handling, we sought to delineate changes in mechanical and relaxation restitution
      produced by heart failure. METHODS AND RESULTS: Six dogs instrumented with left
      ventricular (LV) micromanometers and piezoelectric dimension crystals were
      studied under control conditions and after tachycardia heart failure (THF)
      produced by rapid LV pacing for 3 to 4 weeks. After priming at a basic cycle
      length of 375 ms, test pulses were delivered at graded extrasystolic intervals
      (ESIs). Mechanical response was assessed from single-beat elastance. Relaxation
      was assessed from the time constant of isovolumic relaxation (tau), the average
      rate of pressure fall during isovolumic relaxation (Ravg), and peak negative
      dP/dt, the first derivative of LV pressure. Normalized mechanical and relaxation
      responses plotted against ESI produced monoexponential curves of mechanical and
      relaxation restitution. THF depressed baseline contractile and relaxation
      parameters compared with control (end-systolic elastance, 4.7 +/- 0.4 versus 7.1
      +/- 0.5 mm Hg/mL, P < .005; tau, 34.8 +/- 2.2 versus 26.7 +/- 1.2 ms, P < .05;
      all values mean +/- SEM). THF slowed mechanical restitution and delayed
      development of peak contractile response, with the time constant of mechanical
      restitution increasing from 61.8 +/- 6.9 to 100.2 +/- 9.6 ms, P < .01. THF
      abolished the biphasic behavior of relaxation restitution, and this relation was
      approximated by a single monoexponential function. There was no difference in the
      time constants of the first phase of relaxation restitution at control and after
      THF (TCR1, normalized 1/Ravg, 44.3 +/- 5.6 versus 42.0 +/- 8.5 ms, P = NS; TCR1,
      normalized (dP/dtmin)-1, 42.2 +/- 6.3 versus 36.7 +/- 4.3 ms, P = NS).
      CONCLUSIONS: These results indicate that THF alters the recovery kinetics of SR
      Ca2+ release to a significantly greater extent than those of SR Ca2+
      sequestration and that the abnormal time course of Ca2+ availability to the
      myofilaments is the rate-limiting step in the recovery of cardiac function after
      a depolarization.

PMID- 7805201
TI  - Impact of acute pulmonary rejection on cardiac function.
AB  - BACKGROUND: Experiments were designed to define cardiac function in dogs with
      single lung allografts during acute rejection of the allografted lung. METHODS
      AND RESULTS: Left lungs were either autotransplanted (n = 4) or allotransplanted
      (n = 8) in adult male mongrel dogs. All allotransplanted animals were maintained
      on triple-drug immunosuppression (cyclosporine, azathioprine, and steroids) for 5
      days after the operation. In 4 allotransplanted animals, treatment was
      discontinued, allowing the animals to reject (usually after a further 3 days;
      rejecting group); 4 other allotransplanted animals were maintained on
      immunosuppression for an additional 3 days (immunosuppressed group). Another
      group of dogs were not operated on but were maintained on the same
      immunosuppression as the rejecting group (controls). All experimental animals
      underwent fast computed tomographic scanning with measurement of left ventricular
      pressure and calculation of ventricular chamber volumes, cross-sectional areas of
      coronary arteries, myocardial perfusion, and intramyocardial blood volume.
      Neither cardiac output, left ventricular mass, left ventricular pressure, nor
      myocardial oxygen consumption was altered during acute rejection of lung
      allografts. However, left ventricular contractility (systolic elastance, Emax)
      and ejection fraction were depressed to approximately one half (P < .05) in
      acutely rejecting animals compared with other groups. The cross-sectional area of
      the coronary arteries was less in autotransplanted and allotransplanted treated
      animals than in animals that were not operated on. Cross-sectional area of the
      coronary arteries was decreased by an additional 30% in the rejecting group (P <
      .05). CONCLUSIONS: The results of this study indicate that acute rejection of a
      single lung allograft decreases cardiac performance and reduces diameter of
      coronary arteries in the recipient. Alterations of circulating humoral factors
      and activated leukocytes may contribute to these changes.

PMID- 7805202
TI  - Noninvasive assessment of left ventricular relaxation using continuous-wave
      Doppler aortic regurgitant velocity curve. Its comparative value to the mitral
      regurgitation method.
AB  - BACKGROUND: The most established parameters of left ventricular (LV) relaxation
      are peak negative value of the first derivative of LV pressure (-dP/dtmax) and
      the time constant of isovolumic LV pressure fall. The instantaneous pressure
      gradient between the aorta and the LV during diastole can be calculated from the
      continuous-wave Doppler aortic regurgitant velocity spectrum. Because the
      fluctuation of aortic pressure during LV isovolumic relaxation is negligibly
      minor and because LV minimal pressure is negligibly low, LV pressure during the
      isovolumic relaxation period may be derived from the continuous-wave Doppler
      aortic regurgitant velocity spectrum. This study was designed to clarify whether
      analysis of continuous-wave Doppler aortic regurgitation recording provides
      accurate measures of LV relaxation over a wide range of LV function and to
      determine comparative values of aortic and mitral regurgitation methods in the
      assessment of LV relaxation. METHODS AND RESULTS: In eight mongrel dogs with
      acute ischemic LV dysfunction, the continuous-wave Doppler aortic regurgitant
      velocity spectrum was recorded simultaneously with high-fidelity LV and aortic
      pressures, while the continuous-wave Doppler mitral regurgitant velocity spectrum
      was recorded simultaneously with high-fidelity left atrial and LV pressures. The
      aortic regurgitant velocity spectrum was provided for the determination of
      Doppler-derived mean rate of LV pressure fall in 20 ms after the onset of aortic
      regurgitation (delta P/delta t-AR) and the time interval from the onset of aortic
      regurgitation to the point at (1-1/e)1/2 of the maximal aortic regurgitant
      velocity as an estimate of the time constant. The mitral regurgitant velocity
      spectrum was provided for Doppler-derived mean rate of LV pressure fall in 20 ms
      after the point of -dP/dtmax (delta P/delta t-MR) and the time interval from the
      point of -dP/dtmax to the point with mitral regurgitant velocity of (1/e)1/2 of
      the mitral regurgitant velocity at the point of -dP/dtmax as an estimate of the
      time constant. delta P/delta t-AR and delta P/delta t-MR correlated well with
      catheter-derived -dP/dtmax (r = .92, r = .98, P < .01, respectively). The time
      constant derived from aortic and mitral regurgitant velocity spectra (tau-AR and
      tau-MR) also correlated well with catheter-derived time constant (r = .84, r =
      .76, P < .01, respectively). However, a mean difference of the catheter-derived
      time constant minus tau-MR was larger than tau-AR (29 +/- 30 versus 4 +/- 17 ms,
      P < .01, presented as mean +/- 2 SD). CONCLUSIONS: LV relaxation can be assessed
      from the continuous-wave Doppler aortic regurgitant velocity spectrum. The aortic
      regurgitation method provides an even more accurate estimate of the time constant
      compared with the mitral regurgitation method, particularly in the presence of LV
      dysfunction.

PMID- 7805203
TI  - T lymphocyte activation in stable angina pectoris and after percutaneous
      transluminal coronary angioplasty.
AB  - BACKGROUND: Inflammatory reactions have an important part in atherosclerosis.
      Smooth muscle cells, endothelial cells, monocytes, and T lymphocytes are actively
      involved. The purpose of this study was to assess whether T lymphocytes are
      activated in patients with stable angina pectoris who are candidates for a
      percutaneous transluminal coronary angioplasty (PTCA) and the influence of PTCA
      on this process. METHODS AND RESULTS: Twenty-four patients participated in the
      study. All were 40- to 60-year-old men, and all but one underwent successful
      PTCA. Blood samples were taken 1 day before PTCA and 1 week, 1 month, and 2
      months after. Two groups of patients were detected: group A, 11 patients who had
      high levels of soluble interleukin-2 receptor (sIL-2R) before PTCA that decreased
      toward normal during the follow-up period in most of them; and group B, 13
      patients who did not have elevated sIL-2R levels before PTCA and in whom sIL-2R
      levels did not change after the procedure. Group C consisted of 15 healthy men
      whose sIL-2R levels were in the normal range (control subjects). CONCLUSIONS: (1)
      T lymphocytes are activated in stable angina patients. (2) The level of sIL-2R
      can be a reliable laboratory marker for follow-up of patients after PTCA,
      especially those with high sIL-2R levels before the procedure.

PMID- 7805204
TI  - Premature beats elicit a phase reversal of mechanoelectrical alternans in cat
      ventricular myocytes. A possible mechanism for reentrant arrhythmias.
AB  - BACKGROUND: Alternans of the ST segment of the ECG is an important risk factor
      for sudden cardiac death. Premature beats during alternans and the development of
      discordant alternans are associated with the onset of ventricular tachycardia and
      ventricular fibrillation. Moreover, premature beats can switch the pattern of
      alternans from discordant to concordant alternans. The mechanisms of how a
      premature beat can elicit a pattern shift in alternans and develop malignant
      ventricular arrhythmias are not clear. The purpose of this cellular study was to
      determine the electrical and mechanical restitution properties during cycle
      length-induced alternans and to determine how premature and delayed beats affect
      the resultant phase of alternans. METHODS AND RESULTS: A perforated patch
      recording method and video-based edge detector were used to record action
      potentials and contractions, respectively, from single ventricular myocytes
      enzymatically isolated from the cat heart. Electrical and mechanical restitution
      curves were determined by programmed test beats delivered at different cycle
      lengths during mechanoelectrical alternans. At 35 degrees C, 97.8% of cells
      exhibited concordant cellular alternans (action potentials with the larger action
      potential duration [APD] were associated with the larger contraction, and action
      potentials with the smaller APD exhibited the smaller contraction). The sequence
      or phase of concordant cellular alternans could be systematically reversed by (1)
      early premature beats that followed only action potentials with the shorter APD
      and smaller contraction (type 1 phase reversal; n = 34) or (2) late delayed beats
      that followed only action potentials with the longer duration and the larger
      contraction (type 2 phase reversal; n = 14). A phase reversal point was defined
      as a threshold time interval that resulted in switching the sequence of the
      alternating beats. A test stimulus at the phase reversal point caused temporary
      suppression of mechanoelectrical alternans. Lower temperatures (32 degrees C) or
      decreases in the basic cycle length induced larger beat-to-beat changes in the
      magnitude of alternans (APD or contraction) and significantly shifted the phase
      reversal point to earlier premature intervals for type 1 phase reversal. The
      interval of the phase reversal point was a function of the contractile ratio (the
      magnitude of the larger contraction/smaller contraction for two consecutive
      beats, r = .93) and not the APD ratio (longer APD/shorter APD; r = .501). In
      cells stimulated at cycle lengths longer than the threshold of alternans, a
      single premature beat could elicit a damped form of concordant mechanoelectrical
      alternans. A critically timed second premature beat reversed the phase of the
      damped alternans. CONCLUSIONS: Properly timed premature or delayed beats during
      cycle length-induced alternans consistently reversed the phase of cellular
      mechanoelectrical alternans. Reversal of the phase of alternans was dependent on
      recovery of mechanical activity, not electrical activity. The premature stimulus
      interval at the phase reversal point can be predicted by the magnitude of
      mechanical alternans. Thus, during cycle length-induced alternans, mechanical
      alternans governs the phase of electrical alternans. From the present results, a
      multi-cellular model is proposed that may explain how critically timed premature
      beats cause a regional change in the phase of mechanical alternans and thereby
      result in discordant electrical alternans or dispersion of refractoriness.
      Premature beats that induce phase reversal in mechanoelectrical alternans may
      contribute to the development of reentrant arrhythmias.

PMID- 7805205
TI  - Vasopressin improves vital organ blood flow during closed-chest cardiopulmonary
      resuscitation in pigs.
AB  - BACKGROUND: This study was designed to compare the effects of epinephrine with
      those of vasopressin on vital organ blood flow during closed-chest
      cardiopulmonary resuscitation (CPR) in a pig model of ventricular fibrillation.
      METHODS AND RESULTS: Vasopressin was compared with epinephrine by randomly
      allocating 28 pigs to receive either 0.2 mg/kg epinephrine (n = 7), 0.2 U/kg
      vasopressin (low dose) (n = 7), 0.4 U/kg vasopressin (medium dose) (n = 7), or
      0.8 U/kg vasopressin (high dose) (n = 7) after 4 minutes of ventricular
      fibrillation and 3 minutes of closed-chest CPR. Left ventricular myocardial blood
      flow, determined by use of radiolabeled microspheres during CPR, before and then
      90 seconds and 5 minutes after drug administration was 17 +/- 2, 43 +/- 5, and 22
      +/- 3 mL.min-1.100 g-1 (mean +/- SEM) in the epinephrine group; 18 +/- 2, 50 +/-
      6, and 29 +/- 3 mL.min-1.100 g-1 in the low-dose vasopressin group; 17 +/- 3, 52
      +/- 8, and 52 +/- 6 mL.min-1.100 g-1 in the medium-dose vasopressin group; and 18
      +/- 2, 95 +/- 9, and 57 +/- 6 mL.min-1.100 g-1 in the high-dose vasopressin group
      (P < .001 at 90 seconds and 5 minutes between epinephrine and high-dose
      vasopressin, and P < .01 at 5 minutes between epinephrine and medium-dose
      vasopressin). At the same times, calculated coronary systolic perfusion pressures
      were 12 +/- 2, 36 +/- 5, and 18 +/- 2 mm Hg in the epinephrine group; 10 +/- 1,
      39 +/- 6, and 26 +/- 5 mm Hg in the low-dose vasopressin group; 11 +/- 2, 49 +/-
      6, and 38 +/- 5 mm Hg in the medium-dose vasopressin group; and 10 +/- 2, 70 +/-
      5, and 47 +/- 6 mm Hg in the high-dose vasopressin group (P < .01 at 90 seconds
      and 5 minutes between epinephrine and high-dose vasopressin); and calculated
      coronary diastolic perfusion pressures were 15 +/- 2, 24 +/- 2, and 19 +/- 2 mm
      Hg in the epinephrine group; 13 +/- 1, 25 +/- 2, and 20 +/- 1 mm Hg in the low
      dose vasopressin group; 13 +/- 2, 25 +/- 2, and 21 +/- 2 mm Hg in the medium-dose
      vasopressin group; and 13 +/- 2, 35 +/- 3, and 24 +/- 2 mm Hg in the high-dose
      vasopressin group (P < .05 at 90 seconds between epinephrine and high-dose
      vasopressin). Total cerebral blood flow was significantly higher after high-dose
      vasopressin than after epinephrine (P < .05 at 90 seconds and P < .01 at 5
      minutes between groups). Five animals in the epinephrine, 5 in the low-dose
      vasopressin, 7 in the medium-dose vasopressin, and 6 in the high-dose vasopressin
      groups were successfully resuscitated and survived the 1-hour observation period.
      CONCLUSIONS: We conclude that administration of vasopressin leads to a
      significantly higher coronary perfusion pressure and myocardial blood flow than
      epinephrine during closed-chest CPR in a pig model of ventricular fibrillation.

PMID- 7805206
TI  - Quantitative three-dimensional reconstruction of aneurysmal left ventricles. In
      vitro and in vivo validation.
AB  - BACKGROUND: Current two-dimensional (2D) echocardiographic measures of left
      ventricular (LV) volume are most limited by aneurysmal distortion, which
      restricts application of simple geometric models that assume symmetrical shape.
      2D methods also fail to provide separate volumes of the aneurysm and
      nonaneurysmal residual LV cavity, which could help assess the stroke volume
      wasted by dyskinesis and the potential residual LV body to guide surgical
      approaches and predict their outcome. Three-dimensional (3D) echocardiographic
      reconstruction has potential advantages for assessing aneurysmal left ventricles
      because it is not dependent on geometric assumptions, does not require
      standardized views that may exclude portions of the aneurysm, and can potentially
      measure separate aneurysm and nonaneurysm cavity volumes of any shape. The
      purpose of this study was first, to validate the accuracy of 3D echocardiographic
      reconstruction for quantifying total LV and separate LV body and aneurysm volumes
      in vitro so as to provide direct standards for the separate volumes; and second,
      to determine the feasibility and accuracy of 3D echocardiographic reconstruction
      for quantifying the total volume and function of aneurysmal left ventricles in an
      animal model, providing a reference standard for instantaneous LV volume. METHODS
      AND RESULTS: A recently developed 3D system that automatically combines 2D images
      and their locations was applied (1) to reconstruct 10 aneurysmal ventricular
      phantoms and 12 gel-filled autopsied human hearts with aneurysms, comparing
      cavity volumes (total and aneurysm) to those measured by fluid displacement; and
      (2) to reconstruct the left ventricle during 19 hemodynamic stages in four dogs
      with surgically created LV aneurysms, comparing total volumes with actual
      instantaneous values measured by an intracavitary balloon attached to an external
      column for validation and also calculating the stroke volume wasted by aneurysmal
      dyskinesis. 3D reconstruction reproduced the distorted aneurysmal LV shapes. In
      vitro, calculated volumes (aneurysm, nonaneurysm, and total) agreed well with
      actual values, with correlation coefficients of .99 and SEEs of 3.2 to 6.1 cm3
      for phantoms and 3.4 to 4.2 cm3 for autopsied hearts (mean error, < 4% for both).
      In vivo, LV end-diastolic, end-systolic, and stroke volumes as well as ejection
      fraction calculated by 3D echocardiography correlated well with actual values (r
      = .99, .99, .95, and .99, respectively) and agreed closely with them (SEE = 4.3
      cm3, 3.5 cm3, 1.7 cm3, and 2%, respectively). The stroke volumes wasted by the
      aneurysm were -20.1 +/- 19.3% of LV body (nonaneurysm) stroke volume.
      CONCLUSIONS: Despite distorted ventricular shapes, a recently developed 3D
      echocardiographic system and surfacing algorithm can accurately reconstruct
      aneurysmal left ventricles and quantify total LV volume (validated in vivo and in
      vitro) as well as the separate volumes of the aneurysm and residual LV body
      (validated in vitro). This should improve our ability to evaluate such ventricles
      and guide surgical approaches.

PMID- 7805207
TI  - Anti-cardiolipin antibodies and risk of myocardial infarction in a prospective
      cohort of middle-aged men.
AB  - BACKGROUND: Data concerning the relation between antiphospholipid (aPL)
      antibodies and myocardial infarction in subjects without evidence of overt
      autoimmune disease are conflicting. All published studies have been performed on
      survivors of myocardial infarction or in patients with established coronary heart
      disease. The purpose of the present study was to determine whether the presence
      of aPL antibodies, namely, anti-cardiolipin (aCL) antibodies, carries a risk for
      myocardial infarction in a prospective cohort. METHODS AND RESULTS: The sera to
      be studied were drawn at entry from middle-aged dyslipidemic men (non-high
      density lipoprotein cholesterol, > or = 5.2 mmol/L) participating in the Helsinki
      Heart Study, a 5-year coronary primary prevention trial with gemfibrozil. Samples
      were tested for IgG-class antibodies to cardiolipin by an ELISA. The risk was
      estimated with logistic regression analysis using a nested case-control design
      with 133 patients (myocardial infarction or cardiac death) and 133 control
      subjects, matched for treatment (gemfibrozil/placebo) and geographical area. The
      aCL antibody level, as expressed in optical density units, was significantly
      higher in patients than in control subjects (0.417 versus 0.361; P < .005).
      Subjects with the antibody level in the highest quartile of distribution had a
      relative risk for myocardial infarction of 2.0 (95% confidence interval, 1.1 to
      3.5) compared with the remainder of the population. This risk was independent of
      confounding factors, such as age, smoking, systolic blood pressure, low-density
      lipoprotein (LDL), and high-density lipoprotein. There was a correlation between
      the levels of aCL antibodies and antibodies to oxidized LDL (r = .40, P < .001),
      and their joint effect was additive for the risk. CONCLUSIONS: In a prospective
      cohort of healthy middle-aged men, the presence of a high aCL antibody level is
      an independent risk factor for myocardial infarction or cardiac death. Antibodies
      to cardiolipin and oxidized LDL may, at least in part, represent cross-reactive
      antibody populations.

PMID- 7805208
TI  - 37-year-old woman with progressive fatigue, syncope, and chest pain.

PMID- 7805209
TI  - Images in cardiovascular medicine. Magnetic resonance phase velocity mapping in
      dissecting aortic aneurysm. Demonstration of a proximal intimal tear.

PMID- 7805210
TI  - The cardiac arrhythmia suppression trial. Casting suppression in a different
      light.

PMID- 7805211
TI  - Regulation of nitric oxide production by tetrahydrobiopterin.

PMID- 7805212
TI  - Iron and heart disease: dangers of testing the wrong hypothesis.

PMID- 7805213
TI  - Nonthoracotomy cardioverter-defibrillator implantation by electrophysiologists.

PMID- 7805214
TI  - Electromechanical alternans in the intact heart: physiology and clinical
      relevance.

PMID- 7805215
TI  - Clinicopathological conference.

PMID- 7805216
TI  - Plasmin-mediated activation of contact system in response to pharmacological
      thrombolysis.
AB  - BACKGROUND: Thrombin activity increases in patients treated with coronary
      thrombolysis for acute myocardial infarction, but the mechanisms are not well
      defined. We have shown that thrombin activity increases in plasma and whole blood
      incubated with plasminogen activators and appears to be plasmin mediated and
      dependent on activity of the factor VIIIa/IXa complex. METHODS AND RESULTS: In
      the present study, increases in thrombin activity induced by incubation of
      recalcified citrated plasma with 0.16 to 0.5 mumol/L plasmin at 37 degrees C were
      markedly attenuated in recalcified citrated plasma deficient in factors XI or
      XII, prekallikrein, or high molecular weight kininogen, as well as in plasma
      incubated with plasmin in the presence of 3.5 mumol/L corn trypsin inhibitor, a
      specific factor XIIa inhibitor. Increases in thrombin activity also occurred in
      nonanticoagulated whole blood incubated with pharmacological concentrations of
      plasminogen activators and were markedly attenuated in the presence of corn
      trypsin inhibitor. Plasmin-mediated (0.25 mumol/L) activation of purified factor
      XII occurred in 0.05 mol/L Tris-HCl and 0.012 mol/L NaCl (pH 7.8) at 37 degrees
      C, resulting in equimolar quantities of two fragments that corresponded to
      cleavage of factor XII at Arg353-Val354, the site involved in kallikrein-mediated
      activation of factor XII, and cleavage at Lys346-Ser347, an apparently novel site
      of plasmin-mediated hydrolysis of factor XII. Contact activation was also
      demonstrated in plasma samples from patients after treatment with fibrinolytic
      agents for myocardial infarction, by demonstrating cleavage of high molecular
      weight kininogen from its one-chain to its two-chain form by ligand blotting with
      125I-prekallikrein. CONCLUSIONS: Plasmin-mediated activation of the contact
      system of coagulation appears to account, at least in part, for increases in
      procoagulant activity in patients treated with fibrinolytic agents. It may also
      explain hypotension, by release of bradykinin from high molecular weight
      kininogen, and complement activation, by activated factor XII, that has been
      demonstrated in these patients.

PMID- 7805217
TI  - Previous angina alters in-hospital outcome in TIMI 4. A clinical correlate to
      preconditioning?
AB  - BACKGROUND: Ischemic preconditioning has been shown to reduce myocardial infarct
      size in experimental models, but its role in patients remains unclear. Angina
      before myocardial infarction reflects brief episodes of ischemia and may be a
      marker of preconditioning. As part of the Thrombolysis in Myocardial Infarction
      (TIMI) 4 study, we performed an analysis on the effect of a history of previous
      angina on in-hospital outcomes for patients with acute myocardial infarction.
      METHODS AND RESULTS: Patients eligible for thrombolytic therapy were enrolled
      into the study. Data were collected from case report forms regarding previous
      history of angina, in-hospital outcome and 6-week follow-up. Two hundred eighteen
      patients had a history of previous angina at any time before acute myocardial
      infarction, and 198 patients did not have previous angina. Patients with any
      previous history of angina were less likely than with those without angina to
      experience in-hospital death (3% versus 8%) (P = .03), severe congestive heart
      failure (CHF) or shock (1% versus 7%, P = .006), or the combined end point of in
      hospital death, severe CHF, or shock (4% versus 12%, P = .004). Moreover,
      patients with any history of angina were more likely to have a smaller creatine
      kinase (CK)-determined infarct size (119 versus 154 CK integrated units; P = .01)
      and were less likely to have Q waves on their ECG (57% versus 69%; P = .01). In
      the subset of patients who experienced angina within the 48 hours before
      infarction (compared with those who did not), there was a trend toward less
      likely in-hospital death (3% versus 6%; P = .09), a lower incidence of severe CHF
      or shock (1% versus 6% P = .008), a lower combined end point of death, CHF, or
      shock (3% versus 10%; P = .006), smaller infarct size assessed by CK (115 versus
      151 CK units; P = .03), and a trend toward fewer Q-wave infarcts. However,
      patients with a history of previous angina did have a trend toward more recurrent
      ischemic pain. Of importance is that the beneficial in-hospital effects of
      previous angina were not dependent on angiographically visible coronary
      collaterals. CONCLUSIONS: Previous angina confers a beneficial effect on in
      hospital outcome after acute myocardial infarction. The reasons for this benefit
      are uncertain, but one potential mechanism for this observation may be ischemic
      preconditioning.

PMID- 7805218
TI  - Surgical therapy for coronary artery disease among patients with combined
      coronary artery and peripheral vascular disease.
AB  - BACKGROUND: Among patients with combined coronary artery and peripheral vascular
      disease, long-term benefits of surgical therapy compared with medical therapy for
      coronary artery disease are unknown. METHODS AND RESULTS: Using prospectively
      collected data from the Coronary Artery Surgery Study registry, we performed a
      retrospective cohort analysis of 1834 patients (mean age, 56 years; 20% women)
      with both coronary artery and peripheral vascular disease and evaluated their
      long-term outcomes. Of these patients, 986 received (nonrandomly) coronary artery
      bypass graft surgery, and 848 were treated medically. Perioperative mortality was
      4.2% (2.9% in the absence of peripheral vascular disease; P = .02). In a mean
      follow-up period of 10.4 years, 1100 deaths occurred (80% due to cardiovascular
      causes). For the surgical group, 4-, 8-, 12-, and 16-year estimated probabilities
      of survival were 88%, 72%, 55%, and 41%, respectively, and 73%, 57%, 44%, and
      34%, respectively, for the medical group (P < .0001). Multivariate analysis
      demonstrated that type of therapy was independently associated with survival (P =
      .0001; chi 2 = 15.34). Subgroup analysis suggested that benefits of surgical
      treatment on survival were limited to patients with three-vessel coronary artery
      disease and were inversely related to ejection fraction. Survival free of death
      or myocardial infarction was also significantly better among the surgical group.
      Type of therapy was significantly associated with occurrence of late events (P =
      .01; chi 2 = 6.55). Subgroup analysis again demonstrated that beneficial effects
      of surgery were limited to patients with three-vessel coronary artery disease and
      were inversely related to ejection fraction. CONCLUSIONS: Surgical treatment
      provides long-term benefit for certain subgroups of patients with combined
      coronary artery and peripheral arterial vascular disease.

PMID- 7805219
TI  - Comparison of cost-effectiveness and utility of exercise ECG, single photon
      emission computed tomography, positron emission tomography, and coronary
      angiography for diagnosis of coronary artery disease.
AB  - BACKGROUND: To compare cost-effectiveness and utility of four clinical algorithms
      to diagnose obstructive coronary atherosclerotic heart disease (CAD), we compared
      exercise ECG (ExECG), stress single photon emission computed tomography (SPECT),
      positron emission tomography (PET), and coronary angiography. METHODS AND
      RESULTS: Published data and a straightforward mathematical model based on Bayes'
      theorem were used to compare strategies. Effectiveness was defined as the number
      of patients with diagnosed CAD, and utility was defined as the clinical outcome,
      ie, the number of quality-adjusted life years (QALY) extended by therapy after
      the diagnosis of CAD. Our model used published values for costs, accuracy, and
      complication rates of tests. Analysis of the model indicates the following
      results. (1) The direct cost (fee) for each test differs considerably from total
      cost per delta QALY. (2) As pretest likelihood of CAD (pCAD) in the population
      increases, there is a linear increase in cost per patient tested but a hyperbolic
      decrease in cost per effect and cost per utility unit, ie, increased cost
      effectiveness and decreased cost per utility unit. (3) At pCAD < 0.70, analysis
      of the model indicates that stress PET is the most cost-effective test, with the
      lowest cost per utility, followed by SPECT, ExECG, and angiography, in that
      order. (4) Above a threshold value of pCAD of 0.70 (for example, middle-aged men
      with typical angina), proceeding directly to angiography as the first test showed
      the lowest cost per effect or utility. This quantitative model has the advantage
      of estimating a threshold value of pCAD (0.70) at which the rank order of cost
      effectiveness and cost per utility unit change. The model also allows
      substitution of different values for any variable as a way to account for the
      uncertainties of clinical data, ie, changing costs, test accuracy and risk, etc.
      This procedure, called sensitivity analysis, showed that the rank order of cost
      effectiveness did not change despite changes in several variables. CONCLUSIONS:
      (1) Estimation of total costs of diagnostic tests for CAD requires consideration
      not only of the direct cost of the test per se (eg, test fees) but also of the
      indirect and induced costs of management algorithms based on the test (eg,
      cost/delta QALY). (2) It is essential to consider the clinical history (pCAD)
      when selecting the clinical algorithm to make a diagnosis with the lowest cost
      per effect or cost per utility unit. (3) Stress PET shows the lowest cost per
      effect or cost per utility unit in patients with pCAD < 0.70. (4) Angiography
      shows the lowest cost per effect or cost per utility unit in patients with pCAD >
      0.70.

PMID- 7805220
TI  - Myocarditis in beta-thalassemia major. A cause of heart failure.
AB  - BACKGROUND: Although acute pericarditis is a common complication of beta
      thalassemia major, the prevalence and consequences of myocarditis in this disease
      have not been investigated. METHODS AND RESULTS: A prospective 5-year follow-up
      study was carried out in all patients with beta-thalassemia major in whom the
      diagnosis of acute infectious myocarditis could be established between 1977 and
      1986. A similar number of age- and sex-matched control subjects with beta
      thalassemia and normal left ventricular function and no evidence of myocarditis
      were also followed for 5 years. Of 1048 patients with beta-thalassemia major, 47
      patients (age, 15 +/- 2.5 years) with precordial chest pain were diagnosed as
      having acute infectious myocarditis. Myocardial biopsy was diagnostic in 26
      patients, border-line in 14 patients, and nondiagnostic in 7 patients. Acute
      heart failure with left ventricular dysfunction (left ventricular ejection
      fraction, 25 +/- 11%) developed in 11 patients (23.4%) with myocarditis, and 8 of
      them died within 1 month to 1 year after diagnosis. Thirteen patients with
      myocarditis (27.6%) developed chronic heart failure (left ventricular ejection
      fraction, 26 +/- 13%) within 3 +/- 1.3 years, and 10 of them died within 8 +/- 3
      months. Left ventricular systolic and diastolic functions of the control subjects
      did not change significantly during the 5-year period (left ventricular ejection
      fraction, 63 +/- 11% versus 65 +/- 7%; P = NS). However, left ventricular
      restrictive abnormalities (early diastole/late diastole, > 2.2; deceleration
      time, < 110 milliseconds) combined with right ventricular dilatation (> 30 mm
      internal diameter) and right-sided heart failure developed in 3 patients with
      extremely high mean serum ferritin levels. No significant difference was found in
      mean levels of serum ferritin and pretransfusion hemoglobin between patients with
      and those without myocarditis. CONCLUSIONS: In patients with beta-thalassemia,
      myocarditis appears to be involved in the pathogenesis of left ventricular
      systolic dysfunction, being the main cause of death. Iron overload appears to
      provoke left ventricular restrictive abnormalities combined with right
      ventricular enlargement and dysfunction.

PMID- 7805221
TI  - Association between ease of suppression of ventricular arrhythmia and survival.
AB  - BACKGROUND: We tested the hypothesis that patients whose ventricular arrhythmias
      are easy to suppress have a lower rate of arrhythmic death, defined as arrhythmic
      death and nonfatal cardiac arrest, the primary end point in the Cardiac
      Arrhythmia Suppression Trials (CAST-I and CAST-II), than patients whose
      ventricular arrhythmias are hard to suppress. In addition, we evaluated the
      association between ease of suppression of ventricular arrhythmias and mortality
      of all causes. METHODS AND RESULTS: CAST-I investigated the effect on arrhythmic
      death of ventricular premature depolarization (VPD) suppression achieved by three
      drugs, encainide, flecainide, and moricizine, at two different dose levels; CAST
      II investigated the same effect, using moricizine alone at three dose levels. If
      suppression was achieved, patients were randomized to the effective active drug
      or corresponding placebo. To examine the independence of easily suppressed
      ventricular arrhythmias as a predictor of arrhythmic death, we adjusted
      statistically for other variables that were related both to ease of suppression
      and arrhythmic death. Patients with ventricular arrhythmias (n = 1778) that were
      easy to suppress had fewer arrhythmic deaths during follow-up than those with
      ventricular arrhythmias that were hard to suppress (n = 1173) (relative risk,
      .59; P = .003). Patients whose VPDs were easily suppressed were older and had a
      lower frequency of prior history of heart failure and myocardial infarction. They
      also had a higher incidence of anterior myocardial infarction, VPD frequency, and
      average ejection fraction. After adjusting for these variables, we found that
      easily suppressed ventricular arrhythmias were still significant predictors of
      arrhythmic death (relative risk, .66; P = .013). CONCLUSIONS: This study shows
      that the ease of VPD suppression identifies a subgroup of postmyocardial
      infarction patients who have low risk of arrhythmic death.

PMID- 7805222
TI  - Politics of the demise of healthcare reform.

PMID- 7805223
TI  - Characterization of junctional rhythm after atrioventricular node ablation.
AB  - BACKGROUND: Catheter ablation of the atrioventricular (AV) node with
      radiofrequency current (RFC) is associated with the short-term onset of a
      junctional escape rhythm (JER) in nearly all patients. However, the origin of the
      JER and short-term thermal effects of RFC on this junctional pacemaker activity
      are ill defined. METHODS AND RESULTS: Short-term and noninvasive long-term follow
      up studies were performed to examine the electrophysiological characteristics of
      the underlying JER in 45 patients who had undergone AV nodal ablation with RFC.
      Baseline characteristics and responses to overdrive ventricular pacing and
      intravenous atropine followed by an incremental isoproterenol infusion were
      determined. Short- and long-term responses were compared. HV intervals before and
      after ablation were 49 +/- 9 and 48 +/- 9 milliseconds, respectively (P = NS).
      Follow-up was 11 +/- 8.3 months. JER cycle length was 1526 +/- 298 milliseconds
      in the short-term setting and was present in 44 patients (98%) in the long-term
      setting, measuring 1426 +/- 223 milliseconds (P < .005). Junctional recovery
      times increased exponentially as overdrive pacing rates increased-there was no
      difference between short-term and long-term responses. Drug responses within each
      study were all significant when compared with baseline. However, there was no
      significant difference between short- and long-term responses, except at the
      highest dose of isoproterenol. Intravenous atropine (1 mg) caused an 8.6 +/- 9.3%
      decrease in JER cycle length in the short-term setting compared with a 7.6 +/-
      7.3% decrease in the long-term setting. The decreases in JER cycle length with
      isoproterenol infusion (short-term versus long-term) were 10.1 +/- 9.6% versus
      9.6 +/- 7.4% with 1 microgram/min, 15.8 +/- 11.7% versus 17.4 +/- 8.5% with 2
      micrograms/min, 17.9 +/- 11.2% versus 21.4 +/- 9.1% with 3 micrograms/min (all P
      = NS), and 20.6 +/- 12.1% versus 24.8 +/- 9.1% with 4 micrograms/min (P < .01).
      CONCLUSIONS: Radiofrequency ablation of the AV node is associated with
      development of a JER that is stable in the long-term setting. The lack of change
      in HV interval after ablation locates the junctional pacemaker proximal to the
      central fibrous body. The pattern of drug responses suggests an origin within the
      proximal His bundle at its junction with the AV node rather than the AV node
      itself. The overall similarity between short- and long-term characteristics of
      junctional pacemaker activity mitigates against any reversible thermal effects of
      RFC on this pacemaker focus.

PMID- 7805225
TI  - Importance of initial coronary artery flow after heart procurement to assess
      heart viability before transplantation.
AB  - BACKGROUND: The objective of this study was to evaluate different tests of heart
      viability in a pig model of warm ischemia. METHODS AND RESULTS: Pig hearts (n =
      30) were submitted to 0 (= group I), 10 (group II), 20 (group III), 30 (group
      IV), and 60 (group V) minutes of in situ warm ischemia (animal exsanguination).
      Hearts were removed, then flushed with cardioplegic solution for 3 minutes at a
      fixed pressure of 60 cm H2O, and edema formation, initial coronary flow, and
      ionic composition (Na+, K+, and Ca++) of coronary sinus effluent were evaluated.
      Hearts were then stored for 2 hours in a cold (4 degrees C) preservation
      solution. Myocardial biopsies (and evaluation of energetic index) were performed,
      then the hearts were reperfused for 30 minutes with whole blood with an in vitro
      functional testing system. No edema occurred during cardioplegic flush in the
      hearts in groups I through IV, but a 37 +/- 11% weight increase (P < .001)
      occurred in hearts in group V. There was a progressive decrease in initial
      coronary flow with the increase in the duration of warm ischemia (70 +/- 14
      mL/min per 100 g of tissue in group I and 52 +/- 9, 41 +/- 16, 25 +/- 11, and 23
      +/- 5 mL/min per 100 g, respectively, in groups II through V (P < .01 to P < .001
      versus group I). Initial coronary flow was positively correlated with the
      energetic index (r = .84, P < .001), and the left ventricle developed pressure at
      reperfusion (r = .90, P < .001). Finally, there were significant differences
      between hearts in the control group and those in group V for calcium and sodium
      release (lower in the control group; P < .001 and P < .01, respectively) and for
      potassium removal (lower in group V, P < .05). CONCLUSIONS: These data suggest
      that early measurement of coronary flow after removal of the heart may help to
      assess heart viability before transplantation. This approach may provide a
      comprehensive clinical evaluation to increase the number of hearts available for
      transplantation among those that are rejected in the absence of accurate criteria
      of viability.

PMID- 7805224
TI  - A prospective randomized comparison in humans of biphasic waveform 60-microF and
      120-microF capacitance pulses using a unipolar defibrillation system.
AB  - BACKGROUND: Improving unipolar implantable cardioverter-defibrillator (ICD)
      effectiveness has favorable implications for ICD safety, efficacy, and size.
      Advances in defibrillation efficacy would accelerate ICD ease of use by
      decreasing device size and by minimizing morbidity and mortality related to an
      improved defibrillation safety margin. The specific purpose of the present study
      was to determine whether unipolar defibrillation efficacy could be improved
      further in humans by lowering biphasic waveform capacitance. METHODS AND RESULTS:
      We prospectively and randomly compared the defibrillation efficacy of a 60-microF
      and a 120-microF capacitance asymmetrical 65% tilt biphasic waveform using a
      unipolar defibrillation system in 38 consecutive cardiac arrest survivors before
      implantation of a presently available standard transvenous defibrillation system.
      The right ventricular defibrillation electrode had a 5-cm coil located on a 10.5F
      lead and was used as the anode. The system cathode was the electrically active
      108-cm2 surface area shell (or "can") of a prototype titanium alloy pulse
      generator placed in a left infraclavicular pocket. The defibrillation pulse was
      derived from either a 60-microF or a 120-microF capacitance and was delivered
      from RV-->CAN. Defibrillation threshold (DFT) stored energy, delivered energy,
      leading-edge voltage and current, pulse resistance, and pulse width were measured
      for both capacitances examined. The 60-microF capacitance biphasic pulse resulted
      in a stored-energy DFT of 8.5 +/- 4.1 J and a delivered-energy DFT of 8.4 +/- 4.0
      J. In 34 of 38 patients (89%), the stored-energy DFT was < 15 J. Leading-edge
      voltage at the DFT was 517 +/- 128 V. Mean pulse impedance for the 60-microF
      waveform was 60.6 +/- 7.1 omega. The 120-microF capacitance biphasic pulse
      resulted in a stored-energy DFT of 10.1 +/- 7.4 J and a delivered-energy DFT of
      10.0 +/- 7.2 J (P = .13 and .13, respectively). In 28 of 38 patients (74%), the
      stored-energy DFT was < 15 J (P = .052). Leading-edge voltage at the DFT with the
      120-microF capacitance pulse was 386 +/- 142 (P < .00001). Mean pulse impedance
      for the 120-microF waveform was 60.7 +/- 7.0 omega (P = .80). CONCLUSIONS: The
      results of the present study suggest that a relatively small capacitance, 60
      microF, can be used for unipolar defibrillation systems without compromising
      defibrillation energy requirements compared with more typical ICD capacitance
      values, but this will require a higher circuit voltage. The use of lower
      capacitance also provides a modest increase in the percent of patients who have
      very low energy defibrillation requirements, an important issue should maximum
      ICD energy be decreased from the present level of 34 J. Such a move to smaller
      output devices could allow significant decreases in device size, a necessary
      feature of making cardioverter-defibrillator implantation comparable to that of
      standard pacemaker surgery.

PMID- 7805226
TI  - Beta-adrenergic blocking property of dl-sotalol maintains class III efficacy in
      guinea pig ventricular muscle after isoproterenol.
AB  - BACKGROUND: Catecholamines antagonize the efficacy of several class III
      antiarrhythmic agents. To determine the role of the intrinsic beta-adrenergic
      blocking property of dl-sotalol in maintaining class III efficacy during a high
      catecholamine state, we compared the electrophysiological properties of dl
      sotalol with those of d-sotalol, which is devoid of significant beta-adrenergic
      blocking effect, before and after isoproterenol infusion. METHODS AND RESULTS:
      Action potential duration at 90% repolarization (APD90) was prolonged in isolated
      guinea pig papillary muscles perfused with d-sotalol and dl-sotalol 10(-4) mol/L
      over stimulation cycle lengths from 200 to 2000 ms. The increases in APD90 for d
      sotalol and dl-sotalol over control were 10.9 +/- 2.5 to 23.7 +/- 4.8 ms and 27.9
      +/- 4.0 to 39.0 +/- 5.6 ms, respectively. APD90 shortened to less than control in
      papillary muscles treated with d-sotalol but not dl-sotalol on addition of
      isoproterenol 10(-6) mol/L: -31.2 +/- 3.5 to -18.3 +/- 4.8 ms and 10.5 +/- 3.6 to
      33.3 +/- 7.8 ms, respectively, P < .003. Single guinea pig ventricular myocytes
      were studied by the whole-cell patch clamp method. Time-dependent (Iout) and
      total (Itot) outward current in response to a 300-ms pulse to 20 mV and tail
      current (Itail) to -35 mV were measured after Ca2+ channel block and Na+ channel
      inactivation. Iout, Itail, and Itot were reduced in myocytes perfused with d
      sotalol and dl-sotalol 10(-4) mol/L: Iout, -36.1 +/- 4.1%, -40.5 +/- 3.3%; Itail,
      -59.3 +/- 4.6%, -62.2 +/- 11.1%; Itot, -27.3 +/- 4.3%, -50.0 +/- 11.8%. Iout and
      Itot increased to a greater degree in myocytes treated with d-sotalol than dl
      sotalol on addition of isoproterenol 10(-6) mol/L: Iout, 100.3 +/- 20.6%, 11.3 +/
      7.6%, P = .002; Itot, 86.8 +/- 39.2%, -41.1 +/- 20.9%, P = .01. Itail tended to
      increase more in myocytes treated with d-sotalol than dl-sotalol on addition of
      isoproterenol, but the difference was not significant (-9.1 +/- 13.5%, -28.0 +/-
      9.0%). CONCLUSIONS: The beta-adrenergic blocking property of dl-sotalol maintains
      APD prolongation and repolarizing outward current block during isoproterenol
      infusion in guinea pig ventricular muscle. Extrapolation of these data to a
      clinical setting may explain the efficacy of dl-sotalol in diminishing
      ventricular arrhythmia recurrence.

PMID- 7805227
TI  - Apolipoprotein E polymorphism predicts death from coronary heart disease in a
      longitudinal study of elderly Finnish men.
AB  - BACKGROUND: There is ample evidence from cross-sectional studies of an
      association between allelic variation of the gene coding for apolipoprotein E
      (apoE) and interindividual variation in plasma lipids, and the presence of
      coronary heart disease (CHD). There have been no prospective studies, however, to
      evaluate the usefulness of allelic variation of the apoE gene for predicting CHD.
      METHODS AND RESULTS: Two samples of elderly Finnish men were followed for 5
      years, one in the east (n = 297) and the other in the southwest of Finland (n =
      369). At baseline, when the apoE genotypes were assessed, the men were 65 to 84
      years old. At the end of the follow-up, the vital status of each man was
      determined, and cause of death was coded. At baseline, relative frequencies of
      the three alleles-epsilon 2, epsilon 3, and epsilon 4--were 0.037, 0.827, and
      0.136 in the eastern and 0.062, 0.763, and 0.175 in the southwestern samples,
      respectively (chi 2 = 8.89, df = 2, P < .012 for difference between the samples).
      During the 5-year follow-up, a total of 28 deaths from CHD were recorded in the
      eastern and 42 in the southwestern sample. Relative CHD mortality was not
      heterogeneous between the samples. Among those who died from CHD, there was a
      doubling of the relative epsilon 4 allele frequency in both samples (chi 2 =
      4.70, df = 1, P < .03 for the eastern sample; chi 2 = 7.11, df = 1, P < .01 for
      the southwestern sample). CONCLUSIONS: Allelic variation in the apoE gene is a
      statistically significant predictor of CHD death in these samples of elderly
      Finnish men.

PMID- 7805228
TI  - A DNA variant at the angiotensin-converting enzyme gene locus associates with
      coronary artery disease in the Caerphilly Heart Study.
AB  - BACKGROUND: We analyzed an insertion/deletion (I/D) polymorphism of the
      angiotensin I-converting enzyme (ACE) gene in 1226 subjects from the Caerphilly
      Prospective Heart Disease Study. Amplification of genomic DNA using the
      polymerase chain reaction yielded the genotypes II, ID, and DD. Distribution of
      the polymorphism was analyzed among the whole group and within subgroups
      (specified following multiple risk factor analysis) for coronary artery disease
      (CAD) and against multiple risk factors. METHODS AND RESULTS: Allele frequencies
      were I = 0.413 and D = 0.587. No association was observed between the
      polymorphism and CAD in the whole group. Among subjects defined at lower risk of
      CAD by total cholesterol/HDL cholesterol (TC/HDL) ratios, we found significant
      associations of the DD genotype with CAD (P < .0053, n = 586 for TC/HDL < 5.654
      [median] and P < .009, n = 385 for TC/HDL < 5.0 [clinical threshold]). On further
      exclusion of subjects with blood pressures > or = 140/90 or on hypotensive
      medications, the DD genotype still associated with CAD (P < .07, n = 210, TC/HDL
      < 5.654 and P < .016, n = 135, TC/HDL < 5.0). Further stratification of risk
      incorporating other risk factors, except body mass index, did not alter or
      enhance this association. Although similar association was observed when risk was
      specified by using HDL and apo B levels instead of TC/HDL, this association was
      lost when body mass index was included in the low-risk stratification.
      CONCLUSIONS: The DD genotype is a linkage marker for an etiologic mutation at or
      near the ACE gene that may confer risk of CAD detectable in subjects previously
      unidentifiable with "classic" risk factors. However, this risk may be
      quantitatively small among the general male population.

PMID- 7805229
TI  - Association of fibrinolytic parameters with early atherosclerosis. The ARIC
      Study. Atherosclerosis Risk in Communities Study.
AB  - BACKGROUND: Thrombosis, provoked by a rupture of an atherosclerotic plaque, plays
      a crucial role in precipitating a coronary heart disease event. Its role at the
      early stage of atherosclerosis has, however, been unclear, but it has been
      hypothesized that thrombosis or defective fibrinolysis contributes to the
      progression of atherosclerotic lesions. METHODS AND RESULTS: We studied the
      association of plasminogen activator inhibitor antigen (PAI-1), tissue-type
      plasminogen activator antigen (TPA), and D-dimer with early atherosclerosis in a
      cross-sectional case-control study involving 457 pairs chosen from the biracial
      cohort of the Atherosclerosis Risk in Communities (ARIC) Study. As examined by B
      mode ultrasound, patients (cases) had intima-media thickness of carotid arteries
      above the 90th percentile and control subjects had thickness below the 75th
      percentile of the ARIC cohort. Persons with a history of heart disease, stroke,
      or claudication were excluded from the case-control selection. PAI-1, TPA, and D
      dimer were higher in patients than in control subjects (P < or = .001, Wilcoxon
      signed rank statistic). In conditional logistic regression analyses, the odds
      ratios of carotid atherosclerosis were, for PAI-1, for example, 1.22, 1.54, and
      1.60 in the second, third, and fourth quartiles compared with the first quartile
      (P < .0001, test of linear trend, adjusting for age, systolic blood pressure,
      total cholesterol, acetylsalicylic acid use, and time of blood draw).
      Corresponding tests for D-dimer and TPA also showed an increasing trend (P <
      .0001). CONCLUSIONS: The findings support the hypothesis that thrombosis and
      fibrinolysis play a role at the early stage of the atherosclerotic process.

PMID- 7805230
TI  - Prodromal angina limits infarct size. A role for ischemic preconditioning.
AB  - BACKGROUND: In the experimental setting, it has been demonstrated that
      preconditioning myocardium before prolonged occlusion with brief ischemic
      episodes affords substantial protection to the cells by delaying lethal injury,
      thereby limiting infarct size. Whether the same occurs in humans remains unknown.
      METHODS AND RESULTS: This study was undertaken to determine whether new-onset
      prodromal angina, defined as chest pain episodes limited to the 24 hours before
      myocardial infarction, is the clinical correlate of the ischemic preconditioning
      phenomenon. Twenty-five patients with their first anterior myocardial infarction
      treated with thrombolysis (recombinant tissue plasminogen activator [r-TPA], 100
      mg/3 hours) were retrospectively included in the study because they met the
      following criteria: (1) < 120 minutes from onset of symptoms to reperfusion
      therapy, (2) < 90 minutes from the beginning of thrombolytic therapy to
      reperfusion (defined as rapid ST elevation reduction > 50%), (3) a patient
      infarct-related coronary artery with TIMI 3 flow and complete absence of
      collateral circulation to the infarct related artery (assessed at 24 +/- 5 days),
      and (4) the presence of new-onset prodromal angina, ie, typical chest pain
      episodes occurring at rest within 24 hours or, alternatively, a complete absence
      of symptoms before onset of infarction. Therefore, on the basis of their clinical
      status before infarction, the patients were divided into two groups: group 1, 13
      patients without prodromal angina, and group 2, 12 patients with prodromal
      angina. Despite no difference in time to treatment (81 +/- 19 versus 75 +/- 21
      minutes in group 1 and group 2, respectively; P = NS) and time to reperfusion (58
      +/- 34 versus 46 +/- 24 minutes; P = NS), the peak of CKMB release was markedly
      lower in group 2 (86.3 +/- 66 versus 192.3 +/- 108.3 IU/L; P < .01). In addition,
      although both groups were comparable in terms of area at risk (amount of
      myocardium beyond the infarct-related stenosis; 15.1 +/- 4.6 versus 13.7 +/- 4.6
      hypokinetic segments in group 1 and group 2, respectively, P = NS), the final
      infarct size (11 +/- 7.5 versus 5.6 +/- 4 hypokinetic segments, P < .04) was
      smaller in group 2. Thus, the limitation of the infarct size was significantly
      greater in group 2 (69% versus 36%; P < .05), and this represents an additional
      33% reduction (95% confidence intervals, 7.1% to 58.9%; P = .01) in the group of
      patients with prodromal angina. Also, the third index, that is, the ECG, showed a
      favorable trend toward a lesser number of Q waves and a higher sigma R waves,
      although the values did not reach statistical significance. CONCLUSIONS: Despite
      a similar area at risk, patients with new-onset prodromal angina showed a
      significantly smaller infarct size compared with patients without prodromal
      symptoms. Since the two groups had similar times to reperfusion and no evidence
      of collateral circulation to the infarct related artery, the protection afforded
      by angina in group 2 patients might be explained by the occurrence of ischemic
      preconditioning.

PMID- 7805231
TI  - Effect of cigarette smoking on outcome after thrombolytic therapy for myocardial
      infarction.
AB  - BACKGROUND: Smoking is known to be a strong risk factor for premature
      atherosclerosis, myocardial infarction, and sudden cardiac death. Unexpectedly,
      in the reperfusion era, investigators have reported that patients who smoke have
      a more favorable prognosis after thrombolysis compared with non-smokers. Since
      smoking is associated with a relatively hyper-coagulable state, we hypothesized
      that the coronary occlusion responsible for infarction may be primarily
      thrombotic, with improved outcome relating to enhanced patency or the absence of
      a residual stenosis after thrombolytic therapy. METHODS AND RESULTS: To examine
      this issue, we evaluated 1619 patients treated with TPA, urokinase, or both in
      six consecutive myocardial infarction trials, of whom 878 (54%) were currently
      smoking. Patients underwent 90-minute and predischarge catheterizations, which
      were quantified blinded to the patients' smoking status. As expected, baseline
      fibrinogen (2.8 [2.5,3.6] versus 2.7 [2.4,3.5] g/dL, P = .003) and hematocrit
      (44% [41%, 47%] versus 43% [40%, 45%], P = .0001) levels were greater in smokers.
      Although there were no differences between smokers and nonsmokers with regard to
      90-minute patency (73% versus 74%), smokers were more likely to have TIMI-3 flow
      (41.1% versus 34.6%, P = .034), with a larger minimum lumen diameter of the
      infarct stenosis both acutely (0.82 [0.51, 1.11] versus 0.72 [0.43, 1.04] mm, P =
      .0432) and at follow-up (1.2 [0.8, 1.74] versus 1.0 [0.7, 1.5], P = .002).
      Although smokers tended to have reduced in-hospital mortality compared with
      nonsmokers in univariate analysis (4.0% versus 8.9%, P = .0001), after adjustment
      for baseline differences between smokers and nonsmokers in age (54 [47, 62]
      versus 60 [54, 68] years, P < .0001), inferior infarct location (60% versus 53%,
      P < .0001), three-vessel disease (16% versus 22%, P < .001), and baseline
      ejection fraction (53% [44%, 60%] versus 50% [42%, 58%], P = .0069), smoking
      history was of no independent prognostic significance. CONCLUSIONS: Therefore,
      smokers have a relatively hypercoagulable state, documented by increased
      hematocrit and fibrinogen levels. Quantitative coronary angiographic analysis
      suggests that the mechanism of infarction in smokers is more often thrombosis of
      a less critical atherosclerotic lesion compared with nonsmokers. Enhanced
      perfusion status, as well as favorable baseline clinical and angiographic
      characteristics, may be responsible for the more benign prognosis of current
      smokers.

PMID- 7805232
TI  - Digital subtraction high-frame-rate echocardiography in detecting delayed onset
      of regional left ventricular relaxation in ischemic heart disease.
AB  - BACKGROUND: Because left ventricular (LV) diastolic function is impaired before
      systolic function in patients with ischemic heart disease and because ischemic
      heart disease is constituted of regional rather than global abnormalities of the
      left ventricle, measures of LV regional diastolic dysfunction, if possible,
      should provide the most sensitive assessment of the coronary involved region. The
      objectives of this study are to clarify whether high-frame-rate two-dimensional
      echocardiography, combined with digital subtraction image processing, may be used
      to visualize regional LV relaxation abnormalities in patients with ischemic heart
      disease and to clarify whether this technique provides a measure for the
      noninvasive assessment of the coronary involved region. METHOD AND RESULTS: In 30
      normal subjects and 59 patients with ischemic heart disease, two-dimensional
      echocardiograms obtained at a rate of 60 frames per second were provided on line
      for digital subtraction analysis, with which digitized images were continuously
      subtracted on a frame-by-frame basis. The subtracted images were analyzed to
      determine the onset of the segmental outward motion of the LV wall in early
      diastole in each of 16 segments per subject. Regional relaxation index, defined
      as the interval from the second heart sound to the onset of outward wall motion,
      was significantly prolonged in the coronary involved segments compared with the
      normal segments (36.3 +/- 18.0 versus 101.2 +/- 34.0 ms, P < .01). The
      prolongation in the regional relaxation index was observed even in the coronary
      involved segments without reduction in systolic wall motion. When a cutoff level
      of 50.0 ms was used, coronary involved segments could be distinguished from
      normal or border segments with a sensitivity of 92% and a specificity of 81%.
      CONCLUSIONS: Digital subtraction high-frame-rate echocardiography may be used to
      visualize regional LV relaxation abnormalities in patients with ischemic heart
      disease. The time interval from the second heart sound to the onset of the
      segmental outward motion of the LV wall (regional relaxation index) obtained with
      this technique provides a noninvasive and accurate measure for assessing coronary
      involved regions.

PMID- 7805233
TI  - Myocardial perfusion imaging with 99mTc tetrofosmin. Comparison to 201Tl imaging
      and coronary angiography in a phase III multicenter trial. Tetrofosmin
      International Trial Study Group.
AB  - BACKGROUND: Our objective was to compare the sensitivity and specificity of
      tetrofosmin, a new 99mTc-labeled myocardial perfusion imaging agent for the
      detection of myocardial perfusion abnormalities, with those of 201Tl and coronary
      angiography. Our hypothesis was that same-day stress/rest tetrofosmin imaging
      could provide data comparable to those of 201Tl imaging. Myocardial perfusion
      imaging plays an important role for the evaluation of coronary artery disease.
      Newer 99mTc-labeled agents offer several advantages over 201Tl, the conventional
      myocardial perfusion imaging agent. Tetrofosmin is a new 99mTc-labeled agent with
      promising results in preliminary studies. METHODS AND RESULTS: Two hundred fifty
      two patients with suspected coronary artery disease were enrolled in 10 centers
      in the United States and Europe. All patients underwent exercise and rest
      myocardial perfusion imaging with 99mTc-tetrofosmin using two separate injections
      of the radiotracer 4 hours apart on the same day. Planar images were obtained in
      three standard views 15 to 60 minutes after radiotracer injection. Patients also
      underwent standard exercise and redistribution planar 201Tl imaging within 2
      weeks of tetrofosmin imaging. In addition, 58 healthy subjects with low
      likelihood of coronary artery disease underwent exercise and rest tetrofosmin
      imaging. Coronary angiograms were available in 181 patients with suspected
      coronary artery disease. All radionuclide images were processed in the central
      core laboratory and interpreted blindly by a panel of four experienced readers.
      201Tl images and tetrofosmin images were read separately. Discrepancies were
      resolved by consensus. The workload, peak heart rate, and double products were
      comparable during exercise for both imaging agents. Technically acceptable paired
      201Tl and tetrofosmin images were available in 224 of 252 patients. Tetrofosmin
      images were generally of good quality, with low extracardiac activity, and easy
      to interpret. Patients were categorized as showing normal, ischemia, infarction,
      or mixture with each imaging modality. Precise concordance for each of these
      categories was 59.4% (kappa = 0.44; 95% CI, 0.35 to 0.53). When patients were
      categorized as normal or abnormal, the concordance was 80.4% (kappa = 0.55; 95%
      CI, 0.43 to 0.67). When each of five anatomic territories (septal, anterior,
      inferior, lateral, and apical) was categorized as normal versus abnormal, the
      concordance varied from 81% to 90%. When similar comparison was made for the
      specific category of abnormality, the concordance was 64% to 84%. When coronary
      angiography was used as the criterion, the sensitivity and positive and negative
      predictive accuracy of tetrofosmin and 201Tl were comparable. The normalcy rate
      of tetrofosmin images in the healthy subjects with low likelihood of coronary
      artery disease was 97%. CONCLUSIONS: 99mTc tetrofosmin is a new myocardial
      imaging agent with favorable imaging characteristics with results comparable to
      those of 201Tl.

PMID- 7805234
TI  - Benefit of selective respiratory muscle training on exercise capacity in patients
      with chronic congestive heart failure.
AB  - BACKGROUND: Diminished respiratory muscle strength and endurance have been
      demonstrated in patients with heart failure. This may contribute to exertional
      dyspnea and reduced exercise capacity in these patients. The purpose of this
      study was to investigate whether selective respiratory muscle training could
      alleviate dyspnea and improve exercise performance in patients with chronic
      congestive heart failure. METHODS AND RESULTS: Fourteen patients with chronic
      heart failure (left ventricular ejection fraction, 22 +/- 9%) were enrolled in a
      supervised respiratory muscle training program. This consisted of three weekly
      sessions of isocapnic hyperpnea at maximal sustainable ventilatory capacity,
      resistive breathing, and strength training. Maximum sustainable ventilatory
      capacity, maximum voluntary ventilation, maximal inspiratory and expiratory
      pressures, peak VO2, and the 6-minute walk test were measured before (pre) and
      after (post) 3 months of training. Eight patients completed the training program.
      Respiratory muscle endurance was improved with training, as evidenced by
      increases in maximal sustainable ventilatory capacity (pre, 48.6 +/- 10.7 versus
      post, 76.9 +/- 14.5 L/min; P < .05) and in maximal voluntary ventilation (pre,
      100 +/- 36 versus post, 115 +/- 39 L/min; P < .05). Respiratory muscle strength
      was also increased with training as maximal inspiratory (pre, 64 +/- 31 versus
      post, 78 +/- 33 cm, H2O; P < .01) and expiratory (pre, 94 +/- 30 versus post, 133
      +/- 53 cm H2O; P < .001) pressures rose. Submaximal and maximal exercise capacity
      were significantly improved with selective respiratory muscle training as the 6
      minute walk (pre, 1101 +/- 351 versus post, 1421 +/- 328 ft; P < .001) and peak
      exercise VO2 (pre, 11.4 +/- 3.3 versus post, 13.3 +/- 2.7 mL.kg-1.min-1; P < .05)
      both significantly increased. Dyspnea during activities of daily living was
      subjectively improved in the majority of trained patients. Dyspnea quantified by
      the Borg scale was significantly reduced during progressive isocapnic hypernea
      but not during bicycle exercise. No statistically significant improvement in
      maximal sustainable ventilatory capacity, maximum voluntary ventilation, maximal
      inspiratory or expiratory mouth pressures, 6-minute walk, or peak VO2 was
      observed in the 6 patients who did not complete the training program.
      CONCLUSIONS: Selective respiratory muscle training improves respiratory muscle
      endurance and strength, with an enhancement of submaximal and maximal exercise
      capacity in patients with heart failure. Dyspnea during activities of daily
      living was subjectively improved in the majority of trained patients.

PMID- 7805235
TI  - Dose-dependent effects of the renin inhibitor zankiren HCl after a single oral
      dose in mildly sodium-depleted normotensive subjects.
AB  - BACKGROUND: Zankiren HCl (A-72517) is a potent renin inhibitor shown to have
      substantial bioavailability in several animal species and to produce dose-related
      reductions in blood pressure, plasma renin activity, and angiotensin II (Ang II)
      in salt-depleted dogs. The present study was designed to evaluate the hemodynamic
      effects of oral zankiren HCl administration in healthy volunteers and to
      characterize the response of the renin-angiotensin system (RAS) to specific
      blockade by this new renin inhibitor. METHODS AND RESULTS: Twenty-four male
      volunteers participated in a double-blind randomized, placebo-controlled in
      hospital study to evaluate the effects of zankiren HCl (10 to 250 mg). All
      subjects were pretreated with 40 mg furosemide 12 hours before study drug
      administration. Blood pressure and heart rate were monitored by an automated
      oscillometric device, and blood samples were obtained for active renin, total
      renin, plasma renin activity, angiotensin I (Ang I), Ang II, aldosterone, and
      plasma zankiren concentration. Satisfactory absorption of zankiren HCl was
      demonstrated by the results of plasma drug concentration determinations, and
      renin inhibitory activity was confirmed by dose-related suppression of plasma
      renin activity, Ang I, Ang II, and aldosterone and increases in plasma active
      renin concentration. Furthermore, hypotensive activity was readily observed in
      these normotensive subjects, as evidenced by statistically significant dose
      related blood pressure reductions (P < .01). CONCLUSIONS: Results from this study
      demonstrate for the first time that oral administration of a renin inhibitor can
      dose-dependently decrease blood pressure and circulating components of the RAS in
      normotensive volunteers as a result of documented absorption.

PMID- 7805236
TI  - Comparison of clinical and angiographic outcomes after saphenous vein graft
      angioplasty using coronary versus 'biliary' tubular slotted stents.
AB  - BACKGROUND: Saphenous vein graft (SVG) angioplasty using 15-mm articulated,
      tubular slotted stents results in low (0% to 20%) residual diameter stenoses and
      infrequent (< 5%) major complications. A "biliary" stent design with greater
      radial compressive strength, enhanced visibility, and more variable sizing
      (diameter and length) has been approved for noncoronary indications. A comparison
      of outcomes after coronary versus biliary stent placement in SVG stenoses has not
      been performed. The purpose of this study was to compare the angiographic and
      clinical results after SVG angioplasty using these two balloon-expandable,
      tubular slotted stent designs. METHODS AND RESULTS: During a 3-year period, 231
      patients with 305 SVG lesions were treated using Palmaz-Schatz coronary (n = 108)
      or biliary (n = 123) stents. Cineangiograms were reviewed using qualitative
      morphological and quantitative angiographic methods. Time-dependent clinical
      outcome (freedom from death, Q-wave myocardial infarction, or the need for repeat
      coronary bypass surgery or SVG angioplasty) was assessed using Kaplan-Meier life
      table methods. Unstable angina (P < .001) and recent myocardial infarction (P =
      .001) were present more often in patients undergoing biliary stent versus
      coronary stent placement. Biliary stent-treated SVG lesions were more frequently
      de novo (P = .001), ostial in location (P = .002), > or = 10 mm in length (P =
      .009), thrombus containing (P = .001), and ulcerated (P < .001) than coronary
      stent-treated SVG lesions. Angiographically, biliary stent-treated lesions had
      larger reference vessel diameter (3.43 +/- 0.59 mm versus 3.10 +/- 0.64 mm, P <
      .001), higher balloon-to-artery ratio (1.15 +/- 0.16 mm versus 1.07 +/- 0.19, P =
      .0001), and lower residual diameter stenosis (6 +/- 17% versus 14 +/- 11% in
      coronary stent-treated patients; P < .001). Procedural success rates were high
      (95%), in-hospital major complications were uncommon (< 3%), and follow-up
      clinical outcomes were favorable (6-month event-free survival approximately 80%)
      in both groups. CONCLUSIONS: Despite frequent short-term ischemic syndromes and
      unfavorable lesion characteristics, both biliary and coronary cohorts have
      similarly favorable short-term procedural results and long-term clinical
      outcomes. The increased strut thickness of the biliary stent confers greater
      fluoroscopic visibility and radial compressive strength in exchange for decreased
      stent flexibility and added technical demand in stent deployment. Extreme caution
      is recommended with biliary stent placement in the treatment of SVG lesions as
      clinical results are highly operator dependent.

PMID- 7805237
TI  - Effects of aging on the responsiveness of the human cardiac sympathetic nerves to
      stressors.
AB  - BACKGROUND: Aging increases human sympathetic nervous activity at rest. Beause of
      the probable importance of neural stress responses in the heart as triggers for
      clinical end points of coronary artery disease, it is pertinent to investigate
      whether sympathetic nervous responses to stresses are increased by aging. METHODS
      AND RESULTS: We applied kinetic methods for measuring the fluxes to plasma of
      neurochemicals relevant to sympathetic neurotransmission in younger (aged 20 to
      30 years) and older (aged 60 to 75 years) healthy men during mental stress
      (difficult mental arithmetic), isometric exercise (sustained handgrip), and
      dynamic exercise (supine cycling). The increase in total norepinephrine spillover
      to plasma with mental stress was unaffected by age. In contrast, the increase in
      cardiac norepinephrine spillover was two to three times higher in the older
      subjects (P < .05). The probable mechanism of this higher cardiac norepinephrine
      spillover was reduced neuronal reuptake of the transmitter, because age had no
      influence on the overflow of the norepinephrine precursor,
      dihydroxyphenylalanine, or intraneuronal metabolite, dihydroxyphenylglycol
      (levels of these two substances reflect rates of cardiac norepinephrine synthesis
      and intraneuronal metabolism), and the transcardiac extraction of plasma
      radiolabeled norepinephrine was lower in the older subjects (P < .05). An almost
      identical pattern of neurochemical response was seen with isometric exercise.
      During cycling, total norepinephrine spillover was 16% lower in the older men,
      but cardiac norepinephrine spillover was 53% higher. CONCLUSIONS: Reduced
      norepinephrine reuptake increases the overflow of the neurotransmitter to plasma
      from the aging heart during stimulation of the cardiac sympathetic outflow.
      Failure of transmitter inactivation at postjunctional receptors with aging would
      amplify the neural signal, and in the presence of myocardial disease could
      trigger adverse stress-induced cardiovascular events, particularly when
      accompanied by an age-dependent reduction in vagal tone. Reduction of
      postsynaptic adrenergic responsiveness with aging, however, might protect against
      this, as indicated by our finding that in no case was the heart rate increase
      during stress greater in older men, despite their having larger increases in
      cardiac norepinephrine spillover.

PMID- 7805238
TI  - Endothelin-1 in pulmonary hypertension associated with high-altitude exposure.
AB  - BACKGROUND: Endothelin-1 is involved in chronic pulmonary hypertension. Its role
      in acute pulmonary hypertension due to hypoxia in humans is not clear. We
      therefore studied the influence of hypoxia caused by exposure to high altitude on
      plasma endothelin-1 levels, arterial blood gases, and pulmonary arterial pressure
      in subjects taking nifedipine or placebo. METHODS AND RESULTS: Twenty-two healthy
      volunteers were investigated at low altitude (490 m) and high altitude (4559 m).
      Arterial blood gases were analyzed immediately, endothelin-1 was measured by
      radioimmunoassay, and pulmonary artery pressure was assessed by Doppler
      echocardiography. After baseline investigations, the mountaineers were allocated
      in a randomized double-blind fashion to receive either placebo or nifedipine (20
      mg TID) during rapid ascent to high altitude within 22 hours. Tests were repeated
      at the high-altitude research laboratories located in the Capanna "Regina
      Margherita" (Italy, 4559 m). Plasma endothelin-1 was increased twofold at high
      altitude (5.9 +/- 2.2 pg/mL compared with 2.9 +/- 1.1 pg/mL, P < .05), was
      inversely related to arterial PO2 (r = -.46, P < .001), and correlated with
      pulmonary artery pressure (r = .52, P < .002). At high altitude, arterial
      endothelin-1 was lower (4.3 +/- 1.6 pg/mL) than venous endothelin-1 (5.9 +/= 2.2
      pg/mL, P < .001), indicating either predominant production in the venous
      vasculature or pronounced clearance in the pulmonary circulation. The calcium
      antagonist nifedipine, which lowered pulmonary artery pressure at high altitude
      (32 +/- 5 versus 42 +/- 11 mm Hg, P < .05), had no influence on plasma endothelin
      1 levels. The administration of 35% O2 at high altitude normalized arterial PO2,
      tended to decrease endothelin-1, and decreased pulmonary artery pressure
      accordingly. CONCLUSIONS: We conclude that plasma endothelin-1 is increased at
      high altitude, but whether or not it represents an important pathogenetic factor
      for pulmonary hypertension remains to be investigated.

PMID- 7805239
TI  - The relation of parental cardiovascular disease to risk factors in children and
      young adults. The Bogalusa Heart Study.
AB  - BACKGROUND: Although cardiovascular risk factors relate to family history of
      cardiovascular disease, it is not clear how the relation changes from children to
      young adults. METHODS AND RESULTS: As part of a community study for
      cardiovascular health, parental history of diseases was obtained from 8276
      offspring 5 to 31 years old, 36% black and 64% white. Between 5- to 10-year-old
      children and 25- to 31-year-old young adults, prevalence of parental heart attack
      increased from 5% to 25%. More prevalent in blacks than in whites, parental
      stroke increased from 2% to 9% in whites versus 3% to 19% in blacks; parental
      diabetes rose from 7% to 19% in whites versus 9% to 33% in blacks; and parental
      hypertension increased from 26% to 59% in whites versus 40% to 72% in blacks.
      Offspring with parental heart attack history were significantly overweight after
      10 years of age and showed elevated levels of total cholesterol, VLDL
      cholesterol, LDL cholesterol, insulin, and glucose after 17 years of age,
      irrespective of weight. Offspring of diabetic parents were significantly
      overweight, irrespective of age. They showed significant increases in levels of
      insulin, glucose, triglycerides, total cholesterol, VLDL cholesterol, and LDL
      cholesterol after age 24 years, independent of weight. Offspring of hypertensive
      parents displayed overweight regardless of age, higher levels of blood pressure
      after age 10 years, and elevations of triglycerides and VLDL cholesterol after
      age 24 years irrespective of weight. Analyzed by race and sex in young adults,
      parental heart attack related strongly to LDL cholesterol in the white offspring,
      especially white males, and to insulin in the black offspring. Parental diabetes
      showed a stronger association with overweight and glucose in black females. Also
      noted was the relation between parental hypertension and overweight in black
      females. CONCLUSIONS: Parental history is an important surrogate measure for
      cardiovascular risk in the offspring. However, parental history information alone
      is not sufficient to designate younger children for selective screening for high
      cholesterol, because of the young age of parents.

PMID- 7805240
TI  - Comparison of cardiopulmonary adaptation during exercise in children after the
      atriopulmonary and total cavopulmonary connection Fontan procedures.
AB  - BACKGROUND: There are several potential physiological differences between the
      atriopulmonary (AP) and the total cavopulmonary connection (TCPC) Fontan
      circulations. Studies suggest that the TCPC reduces energy loss due to turbulence
      and may have more dependence on respiratory movement for pulmonary blood flow. We
      compared cardiopulmonary physiology during rest and exercise in patients who had
      undergone the AP Fontan procedure with those who had undergone the TCPC Fontan
      procedure. METHODS AND RESULTS: Forty-three children were studied more than 6
      months after undergoing a Fontan procedure (23 AP and 20 TCPC); 106 healthy
      children were also studied as a control group. Measurements of effective
      pulmonary blood flow, stroke volume, arteriovenous oxygen difference, minute
      ventilation, heart rate, and oxygen and carbon dioxide consumption were made with
      an Innovision quadrupole mass spectrometer. Data from the control group allowed
      calculation of z scores for the Fontan groups matched for age, sex, pubertal
      stage, and body surface area. Maximal exercise performance was equal in the two
      Fontan groups, but it was below normal. However, adaptation to exercise was
      different in the Fontan groups. After 9 minutes of exercise, pulmonary blood flow
      rose less in the AP group than in the TCPC group (P < .01), and the stroke volume
      in the AP group also tended to be lower (P = .057) and their arteriovenous oxygen
      difference was significantly greater (P < .01). Although minute ventilation per
      unit of carbon dioxide production was similar in the Fontan groups at this level
      of exercise, children in the TCPC group breathed faster by approximately 10
      breaths per minute (P < .005). CONCLUSIONS: At submaximal exercise, children who
      had undergone the TCPC Fontan procedure had pulmonary hemodynamics superior to
      those of children who had undergone the AP procedure, largely because of
      respiratory adaptation that permitted blood to be "sucked" into the lungs. To
      achieve the same maximal exercise performance, children who had undergone the AP
      procedure had a superior metabolic adaptation to exercise stress.

PMID- 7805241
TI  - One-stage surgery of coronary arteries and abdominal aorta in patients with
      impaired left ventricular function.
AB  - BACKGROUND: Coronary artery disease (CAD) is common in patients with abdominal
      aortic aneurysms (AAA). Some patients will present with the combination of
      unstable angina, impaired left ventricular function, and a large symptomatic (ie,
      leaking, expanding) AAA. In this subgroup of high-risk patients, aortic cross
      clamping may have a deleterious effect on cardiac function, whereas coronary
      artery bypass graft surgery before aneurysmectomy (staged operation) carries the
      risk of perioperative aneurysm rupture. One-stage surgery, ie, myocardial
      revascularization and simultaneous aortic aneurysm repair, has been proposed in
      this situation. This article summarizes our results with the combined one-stage
      approach in patients with symptomatic CAD, impaired left ventricular function,
      and large symptomatic aortic aneurysms or severe aortic occlusive disease. As
      yet, this cohort is the largest reported in the English literature. METHODS AND
      RESULTS: In 25 patients (24 men) with a mean age of 69.4 years (range, 55 to 80
      years), we performed combined open heart and intra-abdominal aortic surgery.
      Eighteen patients had severe three-vessel disease and impaired left ventricular
      function (ejection fraction, < 35%). In addition, 3 of these patients had severe
      aortic valvular stenosis and/or insufficiency. Seven patients had one- or two
      vessel disease with a low left ventricular ejection fraction in the range of 15%
      to 30%. All patients were in New York Heart Association functional class III or
      IV. Twenty-one of 25 patients had symptomatic infrarenal AAA (perianeurysm
      hematoma was present in 9 patients, and 12 patients had signs of beginning
      perforation). Four patients with aortoiliac occlusive disease and limb ischemia
      were simultaneously operated on. The surgical procedure started with the
      performance of coronary artery bypass graft surgery. After completion of
      myocardial revascularization, aortic aneurysm repair was performed while
      extracorporeal circulation was continued for mechanical cardiac assist until
      aortic surgery was fully accomplished. An average of 3.3 (3 to 5) coronary bypass
      grafts were placed, including 17 internal thoracic artery grafts. In addition,
      three aortic valves were replaced. In the abdominal aortic position, 12 straight
      tube grafts and 13 bifurcation grafts were implanted, and three renal and two
      carotid arteries were simultaneously repaired. The total time of surgery varied
      from 2.3 to 8.5 hours, with a mean time of 3.9 +/- 1.4 hours. One intraoperative
      myocardial infarction occurred despite open grafts. Intensive care unit treatment
      lasted 1 to 13 days, with a mean of 3.6 +/- 2.5 days. Three patients (12%) died
      after surgery--1 because of acute renal failure induced by an adverse reaction to
      heparin, 1 because of myocardial infarction, and 1 because of multiorgan failure.
      One-year actuarial survival rate was 88%, which compares favorably with survival
      after isolated AAA surgery in this high-risk patient subgroup and equals survival
      in patients with severe CAD and severely depressed myocardial function.
      CONCLUSIONS: One-stage surgery is a possible approach to highly symptomatic
      patients with severe multivascular disease and has acceptable early morbidity and
      mortality. Patients with severely impaired left ventricular function and unstable
      CAD carry a high risk of left heart failure and/or myocardial infarction during
      abdominal aortic surgery. Extracorporeal circulation protects the heart from the
      hemodynamic changes after aortic clamping or declamping during abdominal aortic
      surgery. The present study demonstrates that one-stage procedure is a reasonable
      option for this patient subgroup.

PMID- 7805242
TI  - Experimental graft coronary artery disease in a murine heterotopic cardiac
      transplant model.
AB  - BACKGROUND: The development of immunosuppressive therapy has brought about a
      remarkable decrease in the risk of acute cardiac allograft rejection; however,
      the major cause of patient death or retransplantation after the first
      postoperative year is coronary artery disease (CAD) in the graft. The
      pathogenesis and management of CAD are still not clearly established. METHODS AND
      RESULTS: To make an animal model of CAD, we performed primary vascularized
      heterotopic cardiac transplantation using mice. Inbred strains, sharing major
      histocompatibility antigens but differing in minor antigens, were selected. DBA/2
      mice (H-2d) served as donors and B10.D2 mice (H-2d) as recipients. Viability of
      the cardiac grafts was assessed by abdominal palpation. Eight of twelve cardiac
      allografts (67%) survived for 10 weeks after operation without any
      immunosuppressive therapy. Allografts rejected within 4 weeks showed acute
      rejection histologically, whereas allografts surviving more than 4 weeks
      displayed intimal hyperplasia in the coronary arteries, together with
      interstitial and perivascular fibrosis. The severity of intimal thickening in the
      graft coronary artery was then assessed by point counting. In allografts
      surviving for 70 days, intima comprised approximately 42% of the graft arterial
      wall, whereas in DBA/2 and B10.D2 syngeneic grafts, it comprised approximately
      13%. A significant difference in percentage was observed between the intima area
      of allografts and that of syngrafts (P < .01, ANOVA). Long-term oral
      administration of cyclosporine at a dose of 40 mg/kg per day decreased the intima
      area to 34% (P < .05 versus nontreated allografts, ANOVA); however, this dose did
      not affect the incidence of arterial lesions. CONCLUSIONS: The histopathological
      features of DBA/2 allografts surviving for 10 weeks in B10.D2 recipient mice
      mimicked those in human CAD. Using this animal model, the beneficial effect of
      low-dose cyclosporine therapy on CAD was demonstrated, although this effect
      seemed to be limited. This DBA/2-B10.D2 mouse heterotypic cardiac transplant
      model provides valuable results for future studies of the disease.

PMID- 7805243
TI  - Cardioprotective effects of a C1 esterase inhibitor in myocardial ischemia and
      reperfusion.
AB  - BACKGROUND: Myocardial injury after ischemia and reperfusion can be attributed
      largely to the effects of polymorphonuclear leukocytes (PMN). The complement
      system plays an important role as a chemotactic agent, affecting adhesion
      molecule expression and neutrophil accumulation. METHODS AND RESULTS: In the
      present study, the cardioprotective effects of C1 esterase inhibitor (C1 INH)
      were examined in a feline model of myocardial ischemia and reperfusion (90
      minutes of ischemia followed by 270 minutes of reperfusion). C1 INH (15 mg/kg)
      administered 10 minutes before reperfusion significantly attenuated myocardial
      necrosis compared with vehicle (10 +/- 2% and 29 +/- 2% necrosis as a proportion
      of area at risk, respectively; P < .01). Myocardial preservation was also related
      to reduced plasma accumulation of creatine kinase activity. C1 INH treatment
      resulted in improved recovery of cardiac contractility and preservation of
      coronary vascular endothelial function, as assessed by relaxation in response to
      acetylcholine, compared with contractility and preservation of endothelial
      function in vehicle-treated animals (69 +/- 6% and 20 +/- 4% relaxation,
      respectively; P < .01). In addition, cardiac myeloperoxidase activity (an index
      of PMN accumulation) in the ischemic area was significantly reduced after C1 INH
      treatment. Furthermore, immunohistochemical analysis of ischemic-reperfused
      myocardial tissue demonstrated deposition of the first component of the classic
      complement pathway, C1q, on cardiac myocytes and coronary vessels. CONCLUSIONS:
      Blocking of the classic complement pathway by C1 INH appears to be an effective
      means of preserving ischemic myocardium from reperfusion injury. The mechanism of
      this cardioprotective effect appears to be inhibition of PMN-endothelium
      interaction; this inhibition leads to preservation of normal endothelial
      function, which results in reduced cardiac necrosis.

PMID- 7805244
TI  - SC-54684A: an orally active inhibitor of platelet aggregation.
AB  - BACKGROUND: Intravenous therapy has been shown to be beneficial in the prevention
      of acute platelet-associated thrombotic events. However, orally active agents
      would be advantageous for chronic therapy. Fibrinogen receptor antagonists block
      the fibrinogen/platelet interaction and thus inhibit a step required for thrombus
      formation. To date, no orally active fibrinogen binding inhibitors have been
      characterized. SC-54684A, now in clinical trial, is the orally active prodrug of
      a potent and specific fibrinogen binding antagonist. METHODS AND RESULTS: We
      measured inhibition of 125I-fibrinogen binding to activated platelets and
      inhibition of aggregation in platelet-rich plasma to selected agonists and showed
      IC50s of 1.0 x 10(-8) and 3 to 7 x 10(-8) mol/L, respectively. Specificity of the
      active moiety was determined by studying its effect on the binding of (1)
      neutrophils to interleukin (IL)-1 beta-stimulated endothelial cells, (2)
      endothelial cells to fibronectin, and (3) vitronectin to isolated vitronectin and
      fibrinogen receptors. No effect was observed on the binding neutrophils to IL
      stimulated endothelial cells or endothelial cell binding to fibronectin. There
      was a fivefold separation between binding to isolated receptors of vitronectin
      and fibrinogen. Collagen-induced aggregation was inhibited by 80%, and bleeding
      time was increased approximately 2.5-fold when the active moiety was infused to
      steady state at 0.2 micrograms/kg per minute in dogs. When the ester prodrug was
      given orally and the active moiety was given intravenously, the oral systemic
      activity was approximately 20%. Pharmacokinetic analysis after intravenous
      infusion of the prodrug or active moiety showed that the prodrug was rapidly
      converted to the active moiety; the active moiety had a t1/2 of 6.5 hours. When
      the prodrug was administered both orally and intravenously, the systemic
      availability of the active moiety was 62%. CONCLUSIONS: SC-54684A, an orally
      active antiplatelet drug now in clinical trial, is shown to be a potent, specific
      fibrinogen binding inhibitor that blocks platelet aggregation to a wide variety
      of known stimuli and has good bioavailability in animals.

PMID- 7805245
TI  - Extended inhibition of platelet aggregation with the orally active platelet
      inhibitor SC-54684A.
AB  - BACKGROUND: Platelet aggregation is important in thrombotic events, and platelets
      play a major role in the etiology of several cardiovascular diseases. Platelet
      aggregation requires the binding of fibrinogen (fgn) to activated platelets.
      Synthetic peptides modeled after the RGD binding sequence on the fgn alpha-chain
      block the platelet glycoprotein (GP) IIb/IIIa receptor for fgn and effectively
      inhibit aggregation. SC-54684A (SCp, orally active prodrug of the active moiety
      SC-54701, SCa) is a mimetic of the RGD-containing peptide sequence that is
      recognized by the platelet GPIIb/IIIa receptor. SCa blocks the binding of fgn to
      the platelet and therefore prevents platelet aggregation in response to all
      agonists. METHODS AND RESULTS: SCp was administered orally at 1.25, 2.5, 5.0, and
      7.5 mg/kg in a single-dose, dose-ranging study. Blood samples were taken
      periodically for 24 hours, and platelet-rich plasma was prepared and tested for
      inhibition of ex vivo collagen-induced platelet aggregation. The plasma
      concentration of active moiety was determined by bioassay. The time, inhibition,
      and concentration data were used to predict two doses that would result in
      minimum daily inhibition levels of 30% and 70% when administered twice daily (0.6
      and 2.4 mg/kg, respectively). SCp was administered orally to conscious dogs twice
      daily for 14 days (after dose adjustment). Blood samples were obtained at daily
      peak and trough plasma levels (predicted from dose-ranging study). Inhibition of
      ex vivo collagen-induced platelet aggregation and concentration of active moiety
      in the plasma were determined. Average inhibition of platelet aggregation and
      plasma concentration of active moiety amounted to approximately 21% and 14 ng/mL
      at 1.5 mg/kg BID and 75% and 24 ng/mL at 2.4 ng/kg BID at daily minimum plasma
      levels (trough) in steady state. Platelet counts in the 2.4-mg/kg group declined
      from 3.2 x 10(5)/microL to 2.5 x 10(5)/microL in the first 9 days of dosing, with
      no further decline despite continued administration of compound. No changes were
      observed in the animals receiving 1.5 mg/kg. CONCLUSIONS: The results of the dose
      ranging study show that oral administration of SCp results in dose-dependent
      inhibition of platelet aggregation. As shown in the 14-day administration, this
      dose-dependent inhibition can be maintained for an extended period while
      exhibiting no adverse effects. SCp is a leading candidate for development and is
      currently in clinical trials.

PMID- 7805246
TI  - Photodynamic therapy of normal and balloon-injured rat carotid arteries using 5
      amino-levulinic acid.
AB  - BACKGROUND: Although the management of atherosclerotic disease by the use of
      balloon angioplasty is widespread, the treatment is limited by restenosis in 30%
      to 50% of cases. Fibrocellular intimal hyperplasia, the main cause of restenosis,
      arises from proliferation and migration of medial smooth muscle cells (SMC) into
      the intimal layer. Factors leading to intimal hyperplasia are incompletely
      understood, and drugs have universally failed to influence clinical restenosis.
      Photodynamic therapy (PDT), the light activation of photosensitizing drugs to
      generate cytotoxic mediators, may have potential as prophylaxis for intimal
      hyperplasia. 5-Amino-levulinic acid-induced protoporphyrin IX (ALA-PPIX), a
      naturally occurring porphyrin precursor, and its product, -PPIX, offers a novel
      method of sensitization for PDT. We have investigated the pharmacokinetics of ALA
      in arteries and the effects of ALA-PPIX-sensitized PDT on normal and balloon
      injured arteries. METHODS AND RESULTS: ALA (20 to 200 mg/kg) was injected into
      healthy rats, and PPIX fluorescence was measured in the carotid arteries. In a
      second group of rats, the exposed carotid artery was laser illuminated (50 J/cm2,
      630 nm) 30 to 90 minutes after sensitization. Three and 14 days after PDT,
      histological sections from treated arteries were analyzed by light microscopy.
      Subsequently, two new groups of rats underwent PDT (ALA, 100 mg/kg; laser, 50
      J/cm2, 630 nm [at 60 to 90 minutes]). The left carotid arteries underwent balloon
      angioplasty by intraluminal passage of a Fogarty FG2 catheter immediately before
      irradiation. These rats were killed at 14 and 28 days together with laser-only,
      ALA-only, and untreated control rats. The arteries were perfusion-fixed in vivo.
      ALA-PPIX induced arterial media fluorescence in a dose-dependent manner. In the
      normal arteries, PDT produced a dose-dependent cellular depletion in the treated
      arterial segment at 3 days, and this was complete with 100 and 200 mg/kg of ALA.
      At 14 days, the media remained acellular, although the endothelial lining had
      regenerated. In the balloon-injured arteries, PDT produced complete inhibition of
      intimal hyperplasia at both 14 and 28 days (0%). This was significantly greater
      than that produced by any of the control rats (34% to 69% and 37% to 66% at the
      two times, respectively). Significance was at 99% using ANOVA and Fisher's PLSD
      test. No hemorrhage, thrombosis, or aneurysm formation was seen. CONCLUSIONS: ALA
      PPIX-sensitized PDT applied at the time of angioplasty effectively inhibits
      experimental intimal hyperplasia development in rats. This may offer a new
      approach to the management of angioplasty restenosis in patients.

PMID- 7805247
TI  - Effect of left ventricular hypertrophy and its regression on ventricular
      electrophysiology and vulnerability to inducible arrhythmia in the feline heart.
AB  - BACKGROUND: Left ventricular hypertrophy (LVH) is associated with an increased
      risk of death, susceptibility to ventricular arrhythmia, and multiple
      electrophysiological abnormalities. The purpose of the present study was to
      determine whether the susceptibility to arrhythmia and electrical abnormalities
      persists after regression of hypertrophy in an animal model of LVH. METHODS AND
      RESULTS: We placed constricting bands on the ascending aorta of cats (n = 9) or
      performed sham operations (n = 9). Serial cardiac echocardiography was performed
      to measure left ventricular wall thickness. After LVH had developed in the banded
      animals, the constricting bands were removed and serial echocardiograms were used
      to monitor for regression of hypertrophy. Electrophysiological studies were
      performed in cats that showed regression of LVH (Regress, n = 5), those that
      showed no change in LV wall thickness (No Regress, n = 4), and in the sham
      operated animals (Sham). Cats with persistent LVH had a higher incidence of
      inducible polymorphic ventricular tachycardia (4 of 4) compared with Regress (1
      of 5) or Sham (1 of 9) cats (P < .05) and had lower ventricular fibrillation
      thresholds (9 +/- 2 mA) than Regress (17 +/- 4 mA) or Sham (16 +/- 3 mA) cats (P
      < .05). Persistent LVH in the No Regress group was associated with prolongation
      of epicardial monophasic action potential duration (MAPD) in the left but not the
      right ventricle. Dispersion of refractoriness was greater in the No Regress group
      (P < .05 versus Regress or Sham). Regress cats were identical to Sham cats in
      having a low incidence of inducible polymorphic ventricular arrhythmia, high
      fibrillation threshold, and MAPD measurements (P = NS versus Sham). CONCLUSIONS:
      LVH produces multiple electrophysiological abnormalities and increased
      vulnerability to inducible polymorphic ventricular arrhythmia in this model of
      LVH. Cats that show regression of hyperthrophy have normal ventricular
      electrophysiology and have the same low vulnerability to inducible ventricular
      arrhythmia as Sham animals.

PMID- 7805248
TI  - A new solution for life without blood. Asanguineous low-flow perfusion of a whole
      body perfusate during 3 hours of cardiac arrest and profound hypothermia.
AB  - BACKGROUND: The benefits of hypothermia for preventing ischemic injury are well
      known, but its application in surgery to protect the whole body during procedures
      requiring circulatory arrest is currently limited to < 1 hour at 15 degrees C
      using 50% hemodilution. In a significant departure from previous methods, we have
      developed a technique of asanguineous blood substitution with low-flow perfusion
      and cardiac arrest at < 10 degrees C in a canine model. Our approach has been to
      design a hypothermic blood substitute that would protect the brain and visceral
      organs during several hours of bloodless perfusion. Two different solutions have
      been designed to fulfill separate requirements in the procedure. METHODS AND
      RESULTS: With the use of extracorporeal cardiac bypass, 14 adult dogs were
      exsanguinated during cooling; 11 dogs were blood substituted using in combination
      the "purge" and "maintenance" solutions (group 1), and 3 dogs were perfused
      throughout with the "purge" solution alone as controls (group 2). After cardiac
      arrest, the solutions were continuously circulated for 3 1/2 hours by the
      extracorporeal pump (flow rate, 40 to 85 mL.kg-1.min-1; mean arterial blood
      pressure, 25 to 40 mm Hg). The temperature was maintained at < 10 degrees C
      (nadir, 6.6 +/- 0.1 degrees C) for 3 hours, and the hematocrit was kept at < 1%
      before controlled rewarming and autotransfusion. In the experimental group, the
      heart always started spontaneously in the temperature range of 11 degrees C to 27
      degrees C, and 8 animals have survived long-term (current range, 14 to 110 weeks)
      without any detectable neurological deficit. In contrast, two control animals
      survived after extensive and aggressive cardiac resuscitation efforts; after
      surgery they exhibited transient motor and sensory deficits for approximately 1
      week. Evaluation of biochemical and hematological parameters showed only a
      transient and inconsequential elevation in enzymes (eg, brain, liver, cardiac) in
      group 1 compared with the markedly greater elevations in group 2. For example,
      immediate postoperative values (mean +/- SEM) for lactate dehydrogenase were 114
      +/- 10 for group 1 versus 490 +/- 210 for group 2 (P < .03); for SGOT, values
      were 93 +/- 18 for group 1 versus 734 +/- 540 for group 2 (P < .05). On day 1 for
      creatine kinase (CK), the group 1 value was 7841 +/- 2307 versus 71,550 +/- 2658
      for group 2 (P = .03), and for CK-BB, the group 1 value was 108 +/- 22 versus 617
      +/- 154 for group 2 (P = .03). Neurological evaluation using deficit scores (NDS)
      was based on a modification of the Glasgow Coma Scale score: 0, normal; 1,
      minimal abnormality; 2, weakness; 3, paralysis; 4, coma; and 5, death. At days 1
      and 2 after surgery, NDS (mean +/- SEM) were 0 +/- 0 for the experimental group
      versus 1.5 +/- 0.5 for the control group. At days 3 and 7 after surgery, NDS were
      0 +/- 0 for group 1 versus 1.0 +/- 1.0 for group 2. CONCLUSIONS: The faster
      neurological recovery of dogs treated with the "intracellular-type" maintenance
      solution supports the biochemical data showing the benefits of this type of blood
      substitute for extending the safe limits of hypothermic cardiac arrest procedures
      to > 3 hours.

PMID- 7805249
TI  - Improved defibrillation threshold with a new epicardial carbon electrode compared
      with a standard epicardial titanium patch.
AB  - BACKGROUND: Recent studies show that depending on the type of shock morphology
      used, 5% to 15% of patients requiring implantable defibrillators cannot be
      treated with a nonthoracotomy system. In these cases, an epicardial patch-based
      system becomes necessary. In this study, we investigated a newly developed
      epicardial carbon electrode as an alternative to a standard epicardial titanium
      patch. METHODS AND RESULTS: A tubular epicardial braided carbon electrode of 7F
      diameter and 14-cm length applied in a U-shape to the epicardium was compared
      with a standard left ventricular epicardial 15-cm2 titanium mesh patch (CPI Inc).
      As cathode, a CPI endocardial lead, a Medtronic lead, or a carbon-platinum
      iridium prototype electrode was used. Ventricular fibrillation was induced with a
      60-Hz generator and allowed to continue for 10 seconds before a shock was given.
      Two different biphasic shock waveforms (3.2/2- and 6/6-millisecond) were
      delivered by the six electrode configurations. Eight dogs (weight, 24.5 +/- 1.3
      kg) underwent an up-down defibrillation protocol. The order of testing the
      epicardial electrodes, the endocardial cathodes, and the waveform was randomized.
      With the epicardial carbon electrode, the mean defibrillation threshold (DFT)
      energy decreased 39% to 56% and the voltage decreased 24% to 35% compared with
      the titanium patch: from 8.3 +/- 2.5 to 4.9 +/- 3.6 J with the CPI lead and the
      3.2/2-millisecond waveform, from 6.2 +/- 2.5 to 2.9 +/- 2.1 J with the carbon
      platinum-iridium prototype, and from 6.4 +/- 3.4 J to 3.5 +/- 2.6 J with the
      Medtronic lead (P < or = .05). The DFT determinations with the 6/6-millisecond
      biphasic waveform showed a similar trend with slightly higher values.
      CONCLUSIONS: Compared with a titanium patch, the new braided epicardial electrode
      significantly decreases the defibrillation energy requirements. This effect can
      be maximized by using an endocardial carbon-platinum-iridium prototype as cathode
      and a short duration biphasic waveform.

PMID- 7805250
TI  - Pharmacokinetics and regional electrophysiological effects of intracoronary
      amiodarone administration.
AB  - BACKGROUND: The reason for the delay in onset of the electrophysiological effects
      and antiarrhythmic efficacy of amiodarone is not clear. The relation between the
      development of the electrophysiological effects of amiodarone and its myocardial
      concentration is unknown. We therefore examined the time course of development of
      electrophysiological effects during intracoronary infusion of amiodarone and
      related these changes to myocardial concentrations. METHODS AND RESULTS:
      Amiodarone (0.139 mg/min) or normal saline was infused for 10 hours into the
      proximal left anterior descending coronary artery of 24 open-chest dogs. Nineteen
      animals received intracoronary amiodarone and 5 received normal saline (control
      group). Ten of the 19 that received amiodarone underwent electrophysiological
      study (amio-EPS group). Sixteen of the 19, including 7 from the amio-EPS group,
      underwent pharmacological study (PS group). In the amio-EPS group during pacing
      at a cycle length of 300 ms, changes in conduction velocities in drug-exposed
      myocardium referenced to nonexposed myocardium at 1 hour of infusion were -3.7%
      in the longitudinal direction (P = NS) and -7.2% in the transverse direction (P <
      .05); at 3 hours, -12.9% (P < .05) and -9.1% (P < .05); and at 9 hours, -32.9% (P
      < .02) and -31.7% (P < .01). These changes were dependent on amiodarone
      concentration (R2 = .83). There was also an obvious rate-dependent effect that
      was more pronounced for transverse conduction velocities. This effect was also
      dependent on amiodarone concentration. In the PS group, amiodarone levels in the
      drug-exposed myocardium increased from a mean of 5.95 microgram/g at 15 minutes
      of infusion to 188.88 microgram/g at the 10th hour. This increase was time
      dependent (R2 = .91). In the nonexposed myocardium, amiodarone levels were always
      low and increased minimally over time from a mean of 2.68 to 14.45 microgram/g.
      This increase was also time dependent (R2 = .97). CONCLUSIONS: Selective
      intracoronary amiodarone infusion resulted in selective drug accumulation and
      concomitant time-dependent reduction of myocardial conduction velocity. There was
      a significant correlation between the extent of reduction of conduction velocity
      and myocardial amiodarone concentration but not coronary arterial or systemic
      concentration. Repolarization was not significantly altered.

PMID- 7805251
TI  - Sympatholytic action of intravenous amiodarone in the rat heart.
AB  - BACKGROUND: Amiodarone is a commonly used antiarrhythmic agent with complex
      pharmacological effects. Although ventricular arrhythmias can be suppressed soon
      after intravenous amiodarone, the mechanisms responsible for this action are
      unclear. We studied the effects of acute treatment with amiodarone on the
      metabolism and release of norepinephrine (NE) in intact rats and in perfused rat
      hearts. METHODS AND RESULTS: Experiments were performed in anesthetized rats and
      in perfused, innervated hearts with amiodarone administered intravascularly. NE
      release was induced by electrical stimulation of the sympathetic ganglion.
      Concentrations of NE and its intraneuronal metabolite dihydroxyphenylglycol
      (DHPG) in hearts, plasma, and coronary venous effluent were measured by high
      performance liquid chromatography. Acute administration of amiodarone induced
      dose-dependent increases in DHPG concentrations in plasma (5 mg/kg, +48%; 15
      mg/kg, +84%; and 50 mg/kg, +467%) and in coronary venous effluent (1 mumol/L,
      +37%; 3 mumol/L, +510%; and 10 mumol/L, +1100%) together with an unchanged basal
      overflow of NE. In perfused hearts, NE release evoked by nerve stimulation was
      inhibited by infusion of amiodarone (1 mumol/L, -16%; 3 mumol/L, -24%; and 10
      mumol/L, -64%) or by intravenous amiodarone (50 mg/kg) given 1 hour before heart
      perfusion (-70%), and the extent of this suppression correlated well with levels
      of DHPG overflow present immediately before nerve stimulation. When given in
      vitro and in vivo, amiodarone also significantly reduced NE and increased DHPG
      content in the heart, leading to a raised DHPG/NE ratio. All these effects of
      amiodarone were similar to those found with reserpine but less potent. In
      contrast, oral amiodarone produced none of these effects. CONCLUSIONS: Acute
      administration of amiodarone in perfused hearts or intact rats induces partial NE
      depletion in the heart by interfering with vesicular NE storage and enhancing
      intraneuronal NE metabolism, effects associated with an impaired NE release
      during sympathetic activation. Oral dosing with amiodarone has no such effect.
      Further study is required to test whether this novel sympatholytic effect of
      amiodarone contributes to its antiarrhythmic action after intravenous
      administration.

PMID- 7805253
TI  - Does PTCA in acute myocardial infarction affect mortality and reinfarction rates?
      A quantitative overview (meta-analysis) of the randomized clinical trials.
AB  - BACKGROUND: Percutaneous transluminal coronary angioplasty (PTCA) is often
      performed after acute myocardial infarction (AMI) either as an adjuvant to
      thrombolytic therapy or instead of thrombolysis. The effect of PTCA in AMI on
      mortality and reinfarction has remained unclear, with the available randomized
      trials indicating inconsistent results. METHODS AND RESULTS: A systematic
      overview (meta-analysis) of the randomized trials was conducted to assess the
      effect of PTCA in AMI on mortality and reinfarction rates. Data from 7 trials in
      which primary PTCA was evaluated and 16 trials in which PTCA after thrombolysis
      was studied were included in this overview, comprising a total of 8496 patient.
      The trials represented different approaches to the timing of PTCA after AMI. The
      trials of PTCA after thrombolytic therapy were also categorized according to the
      different protocols with respect to the routine or elective character of PTCA in
      the invasive group. A reduction in short-term (6 week) mortality (odds ratio,
      0.56; 95% CI, 0.33, 0.94) and in the combined outcome of short-term mortality and
      nonfatal reinfarction (odds ratio, 0.53; 95% CI, 0.35, 0.80) was observed in the
      trials comparing primary PTCA with thrombolytic therapy. In contrast, in trials
      in which an approach of thrombolysis and PTCA was compared with thrombolytic
      therapy alone, there was no important difference in early mortality, with an
      apparent reduction in mortality between 6 and 52 weeks. The lower mortality
      between 6 and 52 weeks among 6-week survivors seemed to be restricted to the
      subgroup of trials in which PTCA was used as a routine strategy (odds ratio,
      0.58; 95% CI, 0.39, 0.87). CONCLUSIONS: Although the analyses of the various
      categories of trials suggest that primary PTCA may be more beneficial than
      thrombolytic therapy in AMI, these data should be interpreted cautiously unless
      confirmed by larger studies. In contrast, the addition of various other
      strategies of PTCA to thrombolytic therapy does not convincingly indicate a
      clinically different outcome than if a more conservative strategy is followed, in
      which PTCA is used only if clinically indicated. Some specific strategies,
      however, such as rescue PTCA in high-risk patients with occluded arteries, may be
      of benefit.

PMID- 7805252
TI  - Sodium pentobarbital versus alpha-chloralose anesthesia. Experimental production
      of substantially different slopes in the transmural CP/ATP ratios within the left
      ventricle of the canine myocardium.
AB  - BACKGROUND: Transmural analyses of the creatine phosphate (CP)/ATP ratio in
      various lamina of the canine myocardium have previously revealed significant
      variations in the CP/ATP ratio, with the subendocardial layer displaying a
      decreased ratio relative to the subepicardial layer. Without exception, these
      results were obtained under sodium pentobarbital anesthesia. These findings have
      been interpreted to imply that the normal endocardium may be operating in the
      oxygen-limited domain or that there are transmurally varying set points for the
      regulation of oxidative phosphorylation. METHODS AND RESULTS: In this work, we
      examine the effect of the anesthetic regimen on the transmural CP/ATP ratio
      within the left ventricular wall of the canine myocardium using spatially
      localized 31P-nuclear magnetic resonance (NMR) and an open-chest model. Two
      anesthetics were compared, alpha-chloralose and sodium pentobarbital. Under
      sodium pentobarbital, the CP/ATP ratio ranged from 1.92 +/- 0.06 to 2.51 +/- 0.08
      from endocardium to epicardium, resulting in a transmural slope in the CP/ATP
      ratio of 0.149 +/- 0.047 (n = 22). Under alpha-chloralose, CP/ATP ratios ranged
      from 2.18 +/- 0.05 to 2.32 +/- 0.06, with a transmural slope of 0.035 +/- 0.018
      (n = 38). Thus, the transmural slope in CP/ATP ratio was nearly four times
      greater with sodium pentobarbital than with alpha-chloralose, and the difference
      in these slopes was statistically significant (P = .029). No difference was
      observed in average CP/ATP obtained from the entire wall with either anesthetic.
      CONCLUSIONS: These results demonstrate that the transmural trend in CP/ATP ratio
      previously reported in the myocardium is likely to be a direct reflection of the
      sodium pentobarbital anesthetic regimen, not truly reflecting the trend in the
      normal unanesthetized animal. Moreover, since the transmural variation in CP/ATP
      ratio was greatly reduced with alpha-chloralose, it appears unlikely that the
      endocardium in the normal unanesthetized heart is operating in the oxygen-limited
      domain. These results also point to the importance of the anesthetic regimen in
      biochemical analysis, indicate the necessity of increased caution in directly
      translating results obtained under anesthesia, and demonstrate the unique power
      of in vivo NMR to extract such subtle biochemical information.

PMID- 7805254
TI  - American Heart Association-Bugher Foundation Centers for Molecular Biology in the
      Cardiovascular System.
AB  - BACKGROUND: The American Heart Association (AHA) and the Henrietta B. and
      Frederick H. Bugher Foundation in 1985 entered into a partnership to establish a
      group of Centers for Molecular Biology in the Cardiovascular System. The goal was
      to recruit and train young scientists with medical training to apply molecular
      and cellular biology knowledge and techniques to cardiovascular problems. METHODS
      AND RESULTS: Six Centers have been awarded (three in 1986 and three in 1991), and
      a total of 110 trainees have been involved as of June 30, 1994. Of these
      trainees, 77 were recruited and trained by the 1986 Centers. As of June 1994, 88%
      of these trainees remained in academic medicine and 54% progressed to higher
      academic ranks; 79% published papers in science and 66% in molecular biology; and
      36% obtained extramural funding for their work. On this basis, the 1986 trainees
      appear to be well on their way to becoming successful academic cardiologists.
      CONCLUSIONS: The AHA-Bugher Foundation Center program has produced a cadre of
      cardiovascular scientists who are applying molecular biology knowledge to both
      basic and clinical problems.

PMID- 7805255
TI  - Toward a molecular understanding of congenital heart disease.
AB  - BACKGROUND: This review discusses the incidence and importance of congenital
      heart disease (CHD), the reasons that investigation of causative mechanisms for
      human CHD has been slow, and the limitations of the multifactorial theory for the
      etiology of CHD. METHODS AND RESULTS: The molecular defects underlying three
      vasculopathies--Marfan's syndrome (fibrillin), supravalvar aortic stenosis, and
      Williams' syndrome (elastin)--and hereditary telangiectasia are presented to
      emphasize the role of microfibrils and extracellular matrix in the
      pathophysiology of these vascular defects. Animal models of CHD, including situs
      inversus, canine conotruncal malformations, and chick neural crest ablation, are
      examined to emphasize how such studies relate to human CHD, especially by
      pointing to single-gene defects for conotruncal malformations, candidate loci for
      situs inversus, and phenotypic variability caused by neural crest lesions. The
      crucial role of cardiac transcription factors in heart morphogenesis is
      emphasized by review of gene knockout studies of these factors, which cause fetal
      death secondary to heart maldevelopment. Several lines of evidence demonstrating
      genetic etiologies of human CHD are also presented, including the mapping of
      familial atrial septal defects, to prove that one anatomic type of CHD may be due
      to single-gene defects at different loci. Review of atrioventricular canal, both
      secondary to trisomy 21 and as an autosomal-dominant familial defect, reiterates
      this conclusion. The evidence that monosomy on chromosome 22 causes multiple
      types of CHD, including aortic arch and conotruncal defects as part of the CATCH
      22 syndrome, is presented, with results supporting the idea that deletions at
      this site alone may cause 5% of surgically treated CHD. CONCLUSIONS: We conclude
      that (1) human CHD is frequently due to single-gene defects and that even
      sporadic defects may arise from a single-gene abnormality; (2) a common genetic
      defect may cause several apparently different forms of CHD; (3) elucidation of
      the genetic basis of CHD provides clues to normal cardiovascular developmental
      biology; (4) the same cardiac malformation can be caused by mutant genes at
      different loci; and (5) interactions of clinical investigators (cardiologists and
      cardiothoracic surgeons) with basic scientists should allow more rapid progress
      in defining the genetic basis of CHD.

PMID- 7805256
TI  - Genetic basis of lipoprotein disorders.

PMID- 7805257
TI  - Unstable triplet repeat diseases.
AB  - Seven inherited human disorders are now associated with the intragenic expansion
      of triplet repeat DNA sequences. These repeats demonstrate extreme instability in
      both germline and somatic tissue, accounting for the unusual genetic inheritance
      patterns and symptom variability associated with these diseases.

PMID- 7805258
TI  - Genetic models of human vascular disease.
AB  - The use of genetic models has greatly assisted investigations of the natural
      history, mechanisms, and potential therapy for human vascular disease. In the
      past, genetic models of vascular disease were obtained through serendipity and/or
      selective breeding to obtain inbred lines that express the phenotype of interest.
      This approach has yielded several valuable models of atherosclerosis and
      hypertension. In the past several years, the advent of molecular techniques has
      enabled investigators to produce additional novel genetic models of disease that
      have further enhanced the study of vascular biology and medicine. Transgenic
      techniques and the techniques of homologous recombination have allowed
      researchers to alter the genotype of an animal in a precise manner and to study
      the resultant change in phenotype. More recently, techniques of in vivo gene
      transfer have also accelerated and enhanced the development of novel models. The
      application of these methodologies has resulted in important breakthroughs in our
      understanding of the pathogenesis and treatment of vascular diseases. In this
      review, we compare and contrast these technologies along with examples of their
      use in the studies of vascular biology and medicine.

PMID- 7805259
TI  - Molecular basis of familial cardiomyopathies.

PMID- 7805260
TI  - Gene therapy for cardiovascular disease.

PMID- 7805261
TI  - Images in cardiovascular medicine. Vascular ring.

PMID- 7805262
TI  - 'High time' for noninvasive assessment of regional ventricular diastolic ischemic
      dysfunction.

PMID- 7805263
TI  - The growing flood of technetium-99m myocardial perfusion agents. More water ...
      or more mud?

PMID- 7805264
TI  - Exercise intolerance in heart failure. Importance of skeletal muscle.

PMID- 7805265
TI  - Apples, oranges, and restenosis.

PMID- 7805266
TI  - Primary ventricular fibrillation complicating acute myocardial infarction.

PMID- 7805267
TI  - Circadian variation of sustained ventricular tachycardia.

PMID- 7805268
TI  - Vasoreactivity at culprit lesions.

PMID- 7805269
TI  - QTc prolongation and risk of coronary heart disease.

PMID- 7805270
TI  - QT interval predicting for coronary heart disease morbidity.

PMID- 7805271
TI  - Guidelines for carotid endarterectomy. A multidisciplinary consensus statement
      from the Ad Hoc Committee, American Heart Association.
AB  - BACKGROUND AND PURPOSE: Indications for carotid endarterectomy have engendered
      considerable debate among experts and have resulted in publication of
      retrospective reviews, natural history studies, audits of community practice,
      position papers, expert opinion statements, and finally prospective randomized
      trials. The American Heart Association assembled a group of experts in a
      multidisciplinary consensus conference to develop this statement. METHODS: A
      conference was held July 16-18, 1993, in Park City, Utah, that included
      recognized experts in neurology, neurosurgery, vascular surgery, and healthcare
      planning. A program of critical topics was developed, and each expert presented a
      talk and provided the chairman with a summary statement. From these summary
      statements a document was developed and edited onsite to achieve consensus before
      final revision. RESULTS: The first section of this document reviews the natural
      history, methods of patient evaluation, options for medical management, results
      of surgical management, data from position statements, and results to date of
      prospective randomized trials for symptomatic and asymptomatic patients with
      carotid artery disease. The second section divides 96 potential indications for
      carotid endarterectomy, based on surgical risk, into four categories: (1) Proven:
      This is the strongest indication for carotid endarterectomy; data are supported
      by results of prospective contemporary randomized trials. (2) Acceptable but not
      proven: a good indication for operation; supported by promising but not
      scientifically certain data. (3) Uncertain: Data are insufficient to define the
      risk/benefit ratio. (4) Proven inappropriate: Current data are adequate to show
      that the risk of surgery outweighs any benefit. CONCLUSIONS: Indications for
      carotid endarterectomy in symptomatic good-risk patients with a surgeon whose
      surgical morbidity and mortality rate is less than 6% are as follows. (1) Proven:
      one or more TIAs in the past 6 months and carotid stenosis > or = 70% or mild
      stroke within 6 months and a carotid stenosis > or = 70%; (2) acceptable but not
      proven: TIAs within the past 6 months and a stenosis 50% to 69%, progressive
      stroke and a stenosis > or = 70%, mild or moderate stroke in the past 6 months
      and a stenosis 50% to 69%, or carotid endarterectomy ipsilateral to TIAs and a
      stenosis > or = 70% combined with required coronary artery bypass grafting; (3)
      uncertain: TIAs with a stenosis < 50%, mild stroke and stenosis < 50%, TIAs with
      a stenosis < 70% combined with coronary artery bypass grafting, or symptomatic,
      acute carotid thrombosis; (4) proven inappropriate: moderate stroke with stenosis
      < 50%, not on aspirin; single TIA, < 50% stenosis, not on aspirin; high-risk
      patient with multiple TIAs, not on aspirin, stenosis < 50%; high-risk patient,
      mild or moderate stroke, stenosis < 50%, not on aspirin; global ischemic symptoms
      with stenosis < 50%; acute dissection, asymptomatic on heparin. Indications for
      carotid endarterectomy in asymptomatic good-risk patients performed by a surgeon
      whose surgical morbidity and mortality rate is less than 3% are as follows. (1)
      Proven: none. As this statement went to press, the National Institute of
      Neurological Disorders and Stroke issued a clinical advisory stating that the
      Institute has halted the Asymptomatic Carotid Atherosclerosis Study (ACAS)
      because of a clear benefit in favor of surgery for patients with carotid stenosis
      > or = 60% as measured by diameter reduction. When the ACAS report is published,
      this indication will be recategorized as proven. (2) acceptable but not proven:
      stenosis > 75% by linear diameter; (3) uncertain: stenosis > 75% in a high-risk
      patient/surgeon (surgical morbidity and mortality rate > 3%), combined
      carotid/coronary operations, or ulcerative lesions without hemodynamically
      significant stenosis; (4) proven inappropriate: operations with a combined stroke
      morbidity and mortality > 5%.

PMID- 7805272
TI  - Exercise standards. A statement for healthcare professionals from the American
      Heart Association. Writing Group.

PMID- 7805273
TI  - Reversed ratio of color-specific cones in rabbit retinal cell transplants.
AB  - Recently, we have reported on the emergence of various retinal cell types in
      embryonic rabbit retina transplanted to adult rabbits. When comparing the
      relative numbers of the spectrally different cone types in the transplants to
      those in the host or age-matched control retinas, a surprising shift was
      observed. While in the normal rabbit retina the middle-wavelength-sensitive (M)
      cones are considerably more abundant than the short-wave-sensitive (S) cones, the
      S/M cone ratio was found to be the opposite in the graft. The number of rosettes
      containing only S-cones in high density was found to be considerably higher than
      that of M-cone rich rosettes. The number of S-cones also exceeded that of the M
      cones in each rosette that contained both cell types. Our results were obtained
      from the systematic immunocytochemical analysis of 15 different transplants
      derived from transplantations of embryonic rabbit retinas into adult hosts of the
      same species. The emergence and proportion of the two cone types were followed
      between 14 and 63 days after transplantation (between 29 and 78 postconceptional
      days of the donor tissue). Sections from various parts of the transplants were
      reacted with the monoclonal antibodies COS-1 and OS-2, specific for the middle-
      and short-wavelength-sensitive cones, respectively. The explanation for the
      reverse cone ratio in these transplants is not known yet, however, the observed
      phenomenon may indicate differences between the specification of the two basic
      cone types.

PMID- 7805274
TI  - Regional brain blood flow in the ovine fetus during transition to the low-voltage
      electrocortical state.
AB  - Sequential changes in cerebral blood flow and regional distribution were studied
      in nine chronically catheterized fetal sheep during the transition to the low
      voltage ECOG (REM) state to determine the time course for blood flow change
      within the brain and whether executive centres for REM state generation might
      thus be identified. Blood flows were measured during the first, second and third
      minutes after the transition to the low-voltage ECOG state and during the third
      minute of the subsequent high-voltage ECOG (NREM) state using the radioactive
      labelled microsphere technique. Blood flow to the brain was increased during the
      low-voltage REM state when compared to that of the high-voltage NREM state, with
      the increase evident when measured during the first minute after the state
      transition and with no sequential change thereafter. Regional blood flow
      increases during the low-voltage state were greatest to those areas variously
      associated with the generation of REM state activity, but were again remarkably
      stable through the first 3 minutes after the state transition. This rapid
      increase in blood flow within the brain and the regional hierarchy for such,
      supports the participation of multiple anatomical areas which are highly
      integrated and act in concert to give rise to what is known as the REM state.

PMID- 7805275
TI  - Developmental changes of ketamine action against epileptic afterdischarges
      induced by hippocampal stimulation in rats.
AB  - Action of ketamine (5-40 mg/kg) was tested against electrically induced
      hippocampal afterdischarges (four stimulations in one session; 8 Hz, 15 s) in
      rats 7, 12, 18, 25 and 90 days old. In control sessions, there was either stable
      afterdischarge (AD) duration and wet dog shakes (WDS) number or there was an
      increase in ADs' duration with repeated stimulations. Ketamine had dose-dependent
      and age-dependent effects. In 7-18-day-old rats, ketamine suppressed better WDS
      number than AD duration, with nearly absent action on AD duration in 18-day-old
      animals. Ketamine was equipotent for both phenomena in 25-day-old rats and, in
      contrast, it decreased more AD duration than WDS number in 90-day-old rats. The
      data suggest a differentiation induced by ketamine in the expression of motor and
      electrographic phenomena of the experimental seizures.

PMID- 7805276
TI  - Long-term effects of neonatal ovariectomy on cerebellar development in the rat: a
      histological and morphometric study.
AB  - The effects of neonatal ovariectomy on cerebellar development and morphology were
      investigated in rats ovariectomized (OV) or sham-ovariectomized (SOV) 24 h after
      birth. At age 70 days rats were sacrificed and the cerebella processed for
      quantitative light microscopy of matched midline sagittal sections of the vermis.
      Body, brain and cerebellar weights, as well as total cerebellar area and area of
      the internal granular layer were significantly greater in the OV rats. The
      concentration (cells/mm2) and content (cells/section) of granule cells were
      significantly greater in each of the 10 vermal lobules of OV rats. The number of
      Purkinje (P) cells in the OV rats was significantly greater than control values
      for 6 lobules (L-III, L-V, L-VIb,c, L-VII, L-IX and L-X). P cell number for L-I,
      L-II and L-VIII was also higher in the OV group, but not significantly. The
      between group variation for P cell packing density (cells/mm) was significantly
      different, i.e. packing density for the OV rats was greater than the SOV value.
      The most consistent and significant difference between the folial patterns of SOV
      and OV groups was observed in L-VIII, the pyramis. A bilobed L-VIII occurred in
      61.11% of SOV rats, but only in 16.67% of OV rats. Overall, neonatal ovariectomy
      significantly reduced the number of folia. Although the mechanisms are
      speculative, these data clearly indicate removal of the ovaries 24 h after birth,
      either directly and/or indirectly has long-term effects on cerebellar
      development.

PMID- 7805277
TI  - Organizing action of corticosterone on the development of behavioral inhibition
      in the preweanling rat.
AB  - Altricial rat pups develop the ability to freeze and to terminate their emission
      of ultrasonic vocalizations when exposed to an unfamiliar adult male rat. This
      developmental competence in expressing behavioral inhibition is impaired when rat
      pups are adrenalectomized (ADX) on postnatal day 10, a period prior to the
      emergence of behavioral inhibition. Adrenalectomy, however, fails to induce
      similar behavioral deficits when performed after behavioral inhibition has
      developed. Results suggest that adrenal steroids are involved in promoting the
      development but not the activation of behavioral inhibition. To critically test
      this hypothesis, four groups of rats were adrenalectomized on day 10 and tested
      for behavioral inhibition on day 18. Prior to testing, one group of rats received
      daily s.c. injections of vehicle whereas another group was treated with daily
      injections of 3.0 mg/kg of corticosterone (B). The other two groups of rats
      received daily B injections on only days 10-13 or days 14-17. Results indicated
      that ADX rats treated with B only on days 10-13 as well as throughout exhibited
      significantly higher levels of freezing than the other two treatment groups. In
      order to evaluate whether the behavioral inhibitory deficits produced by ADX at
      10 days of age are due to a delayed insensitivity to the 3.0 mg/kg dose of B, day
      10 pups were ADX and injected on days 14-17 with doses of B as high as 12 mg/kg.
      When tested for behavioral inhibition on day 18, these high doses of B were found
      to be ineffective in potentiating freezing above the level of vehicle-treated
      rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7805278
TI  - Developmental pattern of neurotensin content in rat hypothalamic neurons cultured
      in serum-free medium: comparison with in vivo data.
AB  - Neurotensinergic cells were visualized by immunocytochemistry in rat hypothalamic
      cultures grown in serum-free medium for 12 days. They represented 0.03% of the
      total cell population. The pattern observed for the evolution of neurotensin
      content in hypothalamic cultures, from day 5 to day 21 (7-fold increase), was
      similar to that observed in the rat hypothalamus during the corresponding period
      of in vivo ontogeny, from birth to 19 days postnatal (6-fold increase).

PMID- 7805279
TI  - Inhibition of retinal regeneration in larval Rana by an antibody directed against
      a laminin-heparan sulfate proteoglycan.
AB  - In vivo and in vitro experiments have demonstrated that the retinal pigmented
      epithelium can give rise to neuronal precursors during retinal regeneration in
      amphibians. In vitro experiments have further demonstrated that this process is
      greatly facilitated by two molecules associated with basement membranes: laminin
      and fibroblast growth factor. We now report that retinal regeneration can be
      blocked in vivo by an antibody that inhibits the interaction of cells with the
      laminin-heparan sulfate proteoglycan complex. These results further support a
      role for the extracellular matrix in regulating cellular phenotype during retinal
      regeneration.

PMID- 7805280
TI  - Single thalamocortical axons diverge to multiple patches in neonatal auditory
      cortex.
AB  - Thalamic afferents originating in the ventral division of the medial geniculate
      body (vMGB) terminate in patches within lamina III/IV of the primary auditory
      cortex in adult rabbits. Focal iontophoretic injections of the anterograde
      tracer, biocytin, were made into the vMGB of neonatal rabbits to examine the
      morphological organization of auditory thalamocortical (TC) afferents prior to
      hearing onset. TC afferents terminated in distinct patches as early as postnatal
      day 1 (PD-0 = day of birth), 6 days before the behavioral onset of hearing. In
      contrast to TC afferents in adults, the terminal arbors of neonatal vMGB axons
      occupied the entire depth of the cortical plate and lamina I. Serial section
      reconstructions revealed that single vMGB axons in neonates branched to form
      multiple patches within the cortical plate. Collaterals also extended to lamina I
      where they coursed tangentially for several millimeters. An unusual feature of
      the neonatal TC patches was the contribution of descending collaterals from axons
      coursing in lamina I. The presence of distinct patches prior to hearing onset
      indicates that the segregation of auditory TC axons occurs in the absence of
      acoustically driven activity. The extensive postnatal remodeling of TC axons,
      however, may indicate activity-dependent refinement of arbor size.

PMID- 7805281
TI  - Developmental expression of cytokine genes in the cortex and hippocampus of the
      rat central nervous system.
AB  - Cytokines are now considered as constitutive factors of the brain. Some of them
      are involved in the mechanism regulating lineage commitment and cellular
      differentiation of the central nervous system (CNS). We describe here the
      analysis of gene expression in cortex and hippocampus, of interleukin-1 alpha
      (IL1), interleukin-2 (IL2), interleukin-6 (IL6), macrophage-colony stimulating
      factor-1 (MCSF) and monocyte chemoattractant protein-1 (MCP1) in fetal (day 18 of
      gestation; G18), newborn (postnatal day 2; P2), young (postnatal day 21; P21) and
      adult rat using the reverse transcriptase-polymerase chain reaction (RT-PCR). IL6
      and MCP1 mRNA presented distinct patterns of expression levels: IL6 mRNA level is
      most highly expressed in the embryonic cortex, whereas MCP1 is expressed at a
      maximal level in the postnatal day 2 cortical area. In the hippocampus, IL6 is
      most expressed at the adult stage and MCP1 exhibits an equal level of expression
      from day two to the adult stage. However, under our experimental conditions, IL1
      alpha, IL2 and MCSF mRNA were not observed. Thus, certain cytokine genes, each
      with a specific pattern, are expressed in the rat CNS in adult and during
      ontogenesis. These observations suggest that cytokines might be involved as
      regulating factors promoting CNS development.

PMID- 7805282
TI  - Changes in tyrosine hydroxylase gene expression in mesencephalic
      catecholaminergic neurons of immature and adult male rats perinatally exposed to
      cannabinoids.
AB  - We have previously reported that the perinatal exposure of pregnant rats to
      cannabinoids affected the activity of tyrosine hydroxylase (TH) in the striatum
      of their male offspring at peripubertal ages. In the present work, we examined
      whether this effect was accompanied by modifications in TH gene expression. The
      amount of TH-mRNA--measured by Northern blot analysis with a specific TH probe-
      in the mesencephalon of 15- and 20-day-old male rats perinatally exposed to
      hashish extracts was higher than that measured in aged-matched controls. No
      differences appeared at 30 and 40 days after birth, a priori because they
      correspond to ages after the hashish withdrawal occurring on day 24 after birth.
      However, a significant decrease in the amount of TH-mRNA was observed in adult
      animals (70 days of life) perinatally exposed to hashish. The increase in TH-mRNA
      concentrations observed in hashish-exposed 15-day-old animals corresponded to an
      increase in the amount of TH protein, measured by Western blot analysis, in the
      mesencephalon, with no differences in the striatum. However, the amount of TH
      protein in both tissues was not modified by perinatal hashish treatment in adult
      animals, where TH-mRNA amounts had been decreased. In summary, perinatal
      cannabinoid exposure enhances the expression of the TH gene in mesencephalic
      catecholaminergic neurons during early peripubertal ages, coinciding with hashish
      treatment. Normality was found after hashish withdrawal and an interesting
      decrease in the amount of TH-mRNA appeared in adulthood, although with no
      reflection on the amount of TH protein.

PMID- 7805283
TI  - Evidence that molecules influencing axonal growth and termination in the
      developing geniculocortical pathway are conserved between divergent mammalian
      species.
AB  - The general architecture of the visual system is similar for all species of
      mammal. To determine if the development of connections in the visual system might
      be under the influence of conserved molecules, we co-cultured explants of the
      murine lateral geniculate nucleus with slices from either murine or feline
      occipital cortex. Neurite outgrowth from embryonic murine geniculate explants was
      significantly enhanced by slices of newborn mouse occipital cortex or kitten
      visual cortex or by medium previously conditioned by these slices. Slices of
      similar volume but from sites other than occipital cortex had less or no effect
      on the murine geniculate explants. Fibers from murine geniculate explants grew
      freely on cortical slices from the kitten. They terminated mainly in layer 4 and
      also in layer 6, in both murine and feline visual and frontal cortical slices,
      irrespective of whether they entered through the white matter or pial side. Only
      the deep layers of the kitten's cortex sent projections to co-cultured murine
      geniculate explants. We suggest that the diffusible factors released by the
      cortex that stimulate the growth of axons from the lateral geniculate nucleus and
      the molecules that mark specific cortical laminae as targets for ingrowing
      afferents, are conserved in divergent species. We also found that murine
      geniculate axons grew freely on feline cerebellar slices. It is known from
      previous co-culture experiments that rodent geniculate axons are inhibited on
      rodent cerebellum and we suggest that the inhibitory factors involved are not
      conserved.

PMID- 7805284
TI  - Expression of sodium channels with different saxitoxin affinity during rat
      forebrain development.
AB  - This work characterizes the development of the saxitoxin (STX)-sensitive Na+
      channels from rat whole forebrain between embryonic day 15 (E15) and postnatal
      day 90 (P90), both with binding studies and with single channel studies. The Na+
      channel total mRNA and the individual mRNAs encoding Na+ channels I, II and III
      were also determined. The total STX binding rose about 40-fold from E15 to reach
      a plateau at P30 and its temporal course correlated with the expression of Na+
      channel total mRNA. Low affinity and high-affinity STX binding sites, predominant
      in embryonic and postnatal forebrains, respectively, were found. The single
      channel studies of batrachotoxin-modified channels also revealed two main
      populations. In E15 only low-affinity channels (KD = 32.7 nM; 200 mM NaCl) and in
      P30 only high affinity ones (KD = 1.6 nM) were present. At P0 channels with
      intermediate affinity (KD range 3-34 nM) were observed. The increase in affinity
      was due to a gradual increase in the STX association rate.

PMID- 7805285
TI  - Tissue plasminogen activator expression in the embryonic nervous system.
AB  - Tissue plasminogen activator (tPA) expression during embryogenesis was determined
      by in situ hybridization of whole mouse embryos from E10.5 through E17.5. The
      strongest expression occurs in the basal midbrain and hindbrain, and continues
      posteriorly into the neural canal. This expression coincides with extensive cell
      migration and proliferation, and tissue remodelling of this region. tPA mRNA is
      also associated with cells that appear to be invading the cerebellar anlage.
      Presumptive proliferating and migrating cells in the olfactory neuroepithelium
      also express tPA. These results indicate that tPA is expressed by a number of
      different cell types in the developing nervous system and suggest a role for tPA
      in cell migration and tissue remodelling of the developing CNS.

PMID- 7805286
TI  - Effects of maternal lead exposure on functional plasticity in the visual cortex
      and hippocampus of immature rats.
AB  - We examined the amount of long-term potentiation (LTP) in slices from the visual
      cortex and hippocampus of pre- and postnatally lead-exposed rats and controls at
      postnatal days (PND) 12-20. A dietary lead intake of 750 ppm by the dams resulted
      in a mean blood lead concentration in the suckling offspring of about 17'
      micrograms/dl. While high-frequency stimulation (HFS) of the white matter induced
      LTP of the field potentials in layers II/III in cortical slices of ten out of the
      14 control rats, only three of the twelve lead-exposed rats showed a small amount
      of LTP. However, in slices from seven of the twelve lead-exposed rats a long-term
      depression was found following HFS. Furthermore, paired-pulse inhibition was
      weaker in cortical slices from the lead-exposed as compared to the control rats.
      In the CA1 hippocampal region the amount of LTP was significantly reduced in the
      lead-exposed group only in slices taken from rats at PND 16-20, while no
      differences were seen in slices from younger animals. It is concluded that even
      low level lead exposure impairs functions of the visual cortex in the immature
      rat. We suggest that the developing hippocampus is able to compensate for lead
      induced functional deficits in the 2nd postnatal week, being more vulnerable at
      older ages.

PMID- 7805287
TI  - Expression of calcium-binding proteins in the neurotrophin-3-dependent
      subpopulation of rat embryonic dorsal root ganglion cells in culture.
AB  - In this study we have examined the calcium-binding protein expression in rat
      embryonic (E16) dorsal root ganglia (DRG) neurons in vitro in the presence of
      neurotrophin-3 (NT-3). A comparison was made with the expression of calcium
      binding proteins in DRG subpopulations that depended in vitro on nerve growth
      factor (NGF) or brain-derived neurotrophic factor (BDNF). Our results show that
      NT-3 promotes the survival of a DRG subpopulation of which over 75% expresses
      parvalbumin (PV). The majority of these PV-positive NT-3-dependent DRG neurons
      were large 'type A' neurons. Expression of calbindin-D28k (CaBP) and calretinin
      (Calr) in the NT-3-dependent DRG population was seen in smaller fractions
      (between 12 and 17%) of the surviving DRG neurons and in both type A and B
      neurons. The preferential expression of PV in NT-3-dependent type A neurons is
      unique in comparison to the expression of PV and the other calcium-binding
      proteins in DRG neurons surviving in vitro in the presence of NGF or BDNF.

PMID- 7805288
TI  - Expression of the excision repair gene, ERCC3 (excision repair cross
      complementing), during mouse development.
AB  - Expression of the human ERCC3 (excision repair cross-complementing) gene in cells
      from patients with xeroderma pigmentosum (XP) group B (XP-B) corrects the defect
      in repair of UV light-induced DNA damage. XP-B is one of three groups of XP which
      exhibit the clinical symptoms of both XP and Cockayne's Syndrome (CS). CS and XP
      B/CS patients develop severe neurological dysfunction during development. In
      order to explore the link between the defective gene and the neurological
      deficits in XP/CS, we have studied the expression of ERCC3 mRNA in developing
      mice by in situ hybridisation. ERCC3 was found to be ubiquitously expressed in
      cells from all regions and all developmental stages, from 9 day post-coitum
      embryo, to 15 day post-natal brain. In post-natal brain, regional differences in
      expression correlated with cell density and there was no evidence of cell
      specific or developmental alterations in levels of expression. These results
      indicate that the constitutively expressed gene does not perform a discrete
      developmental function. The neurological defects apparent in XP-B are likely to
      arise pleiotypically from the participation of ERCC3 in interactions with other
      elements involved in particular aspects of neurodevelopmental control. These
      results emphasise the developmental importance of genes whose primary functions
      are apparently unconnected with development.

PMID- 7805289
TI  - The formation of glutamatergic synapses in cultured central neurons: selective
      increase in miniature synaptic currents.
AB  - The formation of synapses between cultured rat thalamic neurons was studied with
      electrophysiological and immunocytochemical methods. Thalamic neurons in culture
      form predominantly glutamatergic synapses. Already after 3 days in vitro
      glutamatergic miniature EPSCs occurred spontaneously and their frequency was
      strongly increased after K+ depolarization, while GABAergic mIPSCs were found
      after K+ depolarization at lower frequency. This demonstrates that both,
      excitatory glutamatergic and inhibitory GABAergic synapses were functional in
      close succession to initial neurite outgrowth. Synapses formed independent of
      spontaneous electrical activity, which was absent during the first week in
      culture. Spontaneous action potentials appeared during the second week and
      chronic action potential blockade by addition of tetrodotoxin reduced neuronal
      survival and the number of glutamatergic synapses per neuron. During in vitro
      differentiation the number of synapsin I immunoreactive presynaptic terminals and
      the frequency of spontaneous glutamatergic miniature EPSCs increased closely
      correlated, while the frequency of GABAergic mIPSCs after K+ depolarization did
      not increase. Thus, the continous formation of presynaptic terminals, including
      possible maturation of transmitter release, appeared to underlie the increase in
      mEPSC frequency. Analysis of miniature EPSC amplitudes at different stages in
      vitro revealed an increase in amplitudes, suggesting synaptic differentiation
      after initial establishment of functional transmission in glutamatergic synapses.
      This process was synapse specific as amplitudes of GABAergic mIPSCs were
      invariant.

PMID- 7805290
TI  - The role of conditioning factors in the formation of growth cones and neurites
      from the axon stump after axotomy.
AB  - Knowledge of the cellular events that underlie initiation of outgrowth is crucial
      to understanding regulation of development and regeneration of the nervous
      system. This study utilized a culture preparation in which growth cone formation
      could be studied independent of cellular responses to the presence of
      conditioning factors. Identified neurons were removed from the buccal ganglion of
      the mollusc, Helisoma trivolvis, and plated into defined culture medium. A large
      growth cone formed at the end of the attached axon stump. Although this axonal
      growth cone exhibited filopodial and lamellipodial activity, it did not advance
      across the substrate, suggesting that growth cone formation and motility were
      independent of the presence of conditioning factors. Axonal growth cones of
      identified neurons B19 and B5 exhibited differences in their morphological and
      behavioral properties. In response to the addition of conditioning factors,
      several new neurites extended from the periphery of the axonal growth cone.
      Extension of outgrowth from the axonal growth cone was accompanied by a
      redistribution of cytoskeletal elements in the axonal growth cone. Cytoskeletal
      staining revealed a loss of the peripheral actin filament network and
      microtubules were found to extend into the peripheral lamellipodium of the axonal
      growth cone, an area normally devoid of microtubule staining. Thus, these
      experiments indicate that growth cone formation is an intrinsic property of the
      distal axon stump and that neurite extension from this structure involves
      reorganization of the neuronal cytoskeleton.

PMID- 7805291
TI  - United Nations and nongovernmental organizations. Healthy skin for all.
AB  - The International League of Dermatologic Societies, the International Foundation
      for Dermatology, and the International Society of Dermatology: Tropical,
      Ecological, and Geographic, are the leading nongovernmental dermatology
      organizations that communicate with United Nations agencies such as the World
      Health Organization and UNESCO. The common goal of health for all must include
      healthy skin for all, and it therefore must include concepts such as primary
      health care, disability, wound healing, and advancement of women as well as the
      control and elimination of specific diseases such as leprosy.

PMID- 7805292
TI  - Dermatologic diseases of eastern Africa.
AB  - The countries of eastern Africa are deprived of the most basic of care for their
      skin disease. Diagnostic tools and treatment modalities that are commonplace in
      developed countries are at a bare minimum in these third world nations. In
      addition, there is a dearth of trained dermatologic specialists, especially in
      the arid areas of Kenya and Tanzania. The International Foundation for
      Dermatology was founded in 1987 in an attempt to address this vacuity in medical
      care. During the last 6 years, they have launched a campaign concentrated on the
      activation of Regional Training Centers in Africa, where students will enter a 2
      year training program and graduate with the title of "Dermatology Officer"
      possessing those skills required to treat 80% of common skin diseases. It is
      hoped that this will lead to an increased awareness of skin pathology in general
      and the specific need for trained specialists in underserved areas. However, a
      lack of health care specialists is only part of the problem. Better nutrition,
      clean water, and the education of tribal communities are impending future goals,
      difficult to attain in a nation burdened with economic and political strife.

PMID- 7805293
TI  - Leprosy.
AB  - Leprosy is a chronic infectious disorder, presumptively caused by Mycobacterium
      leprae. This article reviews the epidemiology, etiopathogenesis, classification,
      clinical features, reactions, diagnosis, and treatment of the disease.

PMID- 7805294
TI  - Cutaneous tuberculosis.
AB  - Tuberculosis has been a well-known affliction of mankind since antiquity. This
      article reviews the etiopathogenesis, clinical features, diagnosis, differential
      diagnosis, and treatment of the disease.

PMID- 7805295
TI  - Atypical mycobacterial infections of the skin.
AB  - The term nontuberculosis mycobacteria or environmental mycobacteria should now be
      used rather than atypical mycobacteria. This article reviews the epidemiology and
      prevalence of the infections in humans as well as classifies them into four
      groups.

PMID- 7805296
TI  - Lyme borreliosis.
AB  - Lyme borreliosis is a cutaneous-systemic infection that is generally transmitted
      by a hard-bodied tick and caused by some species of Borrelia, Borrelia
      burgdorferi (sensu stricto), B. garini, and B. afzelii. Lyme borreliosis is a
      widespread disease, present in all continents. It can be divided into an early
      disease, corresponding to the primary stage, and a late disease, including the
      secondary and tertiary stages. The typical cutaneous lesions are erythema
      (chronicum) migrans, lymphadenosis benigna cutis, and acrodermatitis chronica
      atrophicans. The course of Lyme borreliosis depends on the timeliness of both
      diagnosis and antibiotic treatment.

PMID- 7805297
TI  - Superficial fungal infections in the tropics.
AB  - Cutaneous dermatophyte infections are limited to the superficial layers of the
      epidermis. Tropical and subtropical regions of the world provide warm and humid
      climates and therefore a favorable environment for organisms causing superficial
      dermatophyte infections. This article deals with cutaneous dermatophyte
      infections, with particular emphasis on those occurring in tropical regions of
      the world. History, causative organisms, diagnosis, and treatment are discussed.

PMID- 7805298
TI  - Deep fungal infections in the tropics.
AB  - Although tropical deep fungal infections are uncommonly identified in North
      America, these disorders are a diagnostic and therapeutic challenge to the
      clinician. Presented in this article is information on the management of patients
      suffering from mycetoma, chromomycosis, African histoplasmosis, or keloidal
      blastomycosis.

PMID- 7805299
TI  - American mucocutaneous leishmaniasis.
AB  - American mucocutaneous leishmaniasis is produced by several species of
      Leishmania. The microorganism lives in jungle reservoirs and is transmitted by
      sandflies. After infection, a complex set of immunologic phenomena takes place.
      Most lesions tend to heal, but some clinical forms are relentlessly progressive
      and resistant to available therapy. Diagnosis is usually possible with classical
      or modern techniques. Current treatment is effective in most cases, but it is
      expensive and difficult to manage under field conditions. Research on the immune
      response has been interesting, and vaccine prevention and treatment are objects
      of current interest. American leishmaniasis may not always remain a sylvan
      disease, and urban adaptation is a distressing possibility.

PMID- 7805300
TI  - Cutaneous schistosomiasis.
AB  - Schistosomiasis is the name given to a group of diseases caused by trematodes of
      the genus Schistosome. Humans and other animals are definitive hosts, and snails
      of various genera are intermediate hosts. This article reviews the epidemiology,
      pathology, cutaneous manifestations, and treatment of these diseases.

PMID- 7805301
TI  - Filariasis.
AB  - Filariasis is found in many tropical and subtropical countries. Approximately 10%
      of patients with filariasis enter the end stage of the disease known as
      elephantiasis. The obstruction of the lymphatic system leads to massive swelling
      and ulceration, especially of the legs, causing deformity and difficulty in
      movement and function. The condition is preventable with control of the vector
      and early drug therapy.

PMID- 7805302
TI  - Myiasis.
AB  - Myiasis is not an uncommon parasitic infestation in the tropics and subtropics,
      and with the increase in international travel, cases also are encountered outside
      the endemic regions in both Europe and North America. This article reviews the
      ecology, classification, pathophysiology, pathology, and treatment of myiasis.

PMID- 7805303
TI  - Sexually transmitted diseases from the tropics. An overview.
AB  - The tropical ecosystem as related to sexually transmitted diseases and their
      epidemiology is outlined in this article. The predominance of first-generation
      bacterial STDs with more florid presentations, together with a back-ground of
      more covert infections, such as with Chlamydia and human papillomavirus, are
      noted. Presentations of infections in people returning from the tropics are
      highlighted, and particular features of the various infections relevant to their
      tropical origin are discussed. The overview can only hint at the wide diversity
      of infections and presentations from the tropics and the challenge in both
      diagnosis and control that they present.

PMID- 7805304
TI  - AIDS in the tropics.
AB  - The epidemiology and clinical manifestations of AIDS in the tropics differ
      considerably from classic descriptions of the disease. Clinical features are
      reviewed in this article, with emphasis on infectious and nutritional
      manifestations. Management strategy in the tropics also is outlined.

PMID- 7805305
TI  - Genital ulcer disease.
AB  - There are five major sexually transmitted diseases producing genital ulcerations.
      Their prevalence varies among geographic regions. Whereas genital herpes is the
      most frequent cause of genital ulcer in western Europe and North America, the
      most common cause of genital ulcer disease in developing countries appears to be
      chancroid. Owing to frequently atypical presentation and mixed infections, an
      accurate clinical diagnosis is very difficult. Successful management of genital
      ulcer disease depends on accurate diagnosis corroborated by performance of
      appropriate laboratory tests when possible.

PMID- 7805306
TI  - Brazilian pemphigus foliaceus, endemic pemphigus foliaceus, or fogo selvagem
      (wild fire).
AB  - Brazilian pemphigus foliaceus, also known as fogo selvagem, is the endemic form
      of pemphigus foliaceus occurring in certain regions of Brazil. Epidemiologic data
      strongly support the notion that this disease is caused by exposure to an
      environmental agent or agents. This form of pemphigus foliaceus is a true human
      autoimmune disease mediated by autoantibodies of the IgG class, IgG4 subclass.
      These autoantibodies are pathogenic and highly specific for the disease. The
      environment agent may sensitize the patient to produce autoantibodies. These
      autoantibodies may cross-react with the epidermis and induce disease in the
      patient.

PMID- 7805307
TI  - Pigmentary problems in the tropics.
AB  - Pigmentary problems are one of the most frequent causes of dermatologic
      consultation in the tropics. This article deals with diseases seen mostly in
      tropical countries (ashy dermatosis, lichen planus pigmentosus, frictional
      dermatitis, pityriasis versicolor, and pinta) and in which a combination of
      racial, ecologic, nutritional, and social factors all contribute. Other common
      dermatoses seen worldwide, such as vitiligo and melasma, sometimes acquire
      dramatic expressions in tropical countries, and their management is usually
      difficult even for the most experienced dermatologists.

PMID- 7805308
TI  - Genodermatoses.
AB  - This article describes some of the genodermatoses encountered in the black
      populations in Africa, starting with ainhum, which appears to be genetically
      determined. Palmoplantar keratodermas are common in Africa but are difficult to
      classify and their hereditary nature is not always recognized. Of the ichthyoses,
      the lamellar type is commonest, with the so-called bathing-suit distribution
      apparently unique to Africans. Albinism and xeroderma pigmentosum are important
      causes of cutaneous malignancy in the tropics. Neurofibromatosis and tuberous
      sclerosis are relatively common, whereas hypermelanosis of Ito is rare but easy
      to recognize in dark skin.

PMID- 7805309
TI  - Photodermatoses.
AB  - Exposure to ultraviolet light is an important factor in precipitating or
      potentiating a number of cutaneous lesions and may also exacerbate generalized
      systemic disease activity. Although the role of ultraviolet light is clearly
      defined in some conditions, its pathogenic role in others is less understood. The
      approach to this group of diseases in tropical countries differs from that in the
      Occidental countries. It is important to emphasize the increased sunlight, not
      only its intensity but its duration throughout the year. On the other hand, the
      pigmentary variation seen in these areas provides a natural protection against
      some of these diseases. In some cases, treatment is less sophisticated than in
      developed countries. In others, the high cost of drugs does not permit their use,
      and the prophylactic approach is photoprotection.

PMID- 7805310
TI  - Psoriasis in the tropics. Epidemiologic, genetic, clinical, and therapeutic
      aspects.
AB  - There is a dearth of information on psoriasis in the tropics. Psoriasis occurs
      more frequently in northern geographic regions than in tropical climates. Its
      prevalence varies not only within the ethnic groups of a country but from country
      to country. A review of published studies on the natural history of psoriasis in
      the tropics is presented in this article.

PMID- 7805311
TI  - Choosing a local anesthetic.
AB  - Although lidocaine alone will serve as an excellent anesthetic for most patients,
      using less painful injectable agents, topical anesthetics, and occasionally oral
      sedation will offer the frightened or pain-intolerant patient an acceptable and
      effective alternative system of local anesthesia. The pain-tolerant patient will
      also appreciate the reduced discomfort experienced when these products and
      techniques are employed. Uses and practical considerations of the agents in this
      system are summarized in Table 2.

PMID- 7805312
TI  - Well differentiated astrocytoma occurring nine years after radiation therapy for
      medulloblastoma.
AB  - Conventional treatment for medulloblastoma includes surgical resection followed
      by craniospinal irradiation, with the potential risk of subsequent radiotherapy
      induced secondary neoplasms. We report a 23-year-old woman previously irradiated
      nine years earlier for a cerebellar medulloblastoma who developed a new enhancing
      lesion in the primary radiation field four weeks following completion of high
      dose chemotherapy with bone marrow transplantation for recurrent disease.
      Resection of this lesion revealed a low grade glioma with no evidence of
      recurrent medulloblastoma.

PMID- 7805313
TI  - Neural regulation of acid maltase in an unusual adult onset deficiency.
AB  - In a 48-year-old female, the first symptoms apparently manifested themselves 18
      years before, with occasional tripping and weakness in both legs. During the next
      18 years, weakness progressed and the patient developed a waddling gait; she
      became unable to rise from a lying or seated position unassisted and the shoulder
      girdle also became affected. Neurological examination revealed limb and shoulder
      girdle predominantly involving the lower extremities. We established cell
      cultures from muscle biopsy specimens obtained from our patient and carried out
      morphological analysis which, although aspecific, demonstrated clear signs of
      neurogenic suffering. This was confirmed in EMG studies performed. Biochemical
      analysis revealed very low acid maltase residual activity. We describe an unusual
      case of adult-onset acid maltase deficiency (AMD) with neurogenic atrophy and low
      residual activity. Innervated myofibres prepared by co-culturing the patient's
      myoblasts, with spinal cord foetal mouse explants were not associated with an
      abnormal in vitro maturation of the innervated myofibres as expected by the very
      low residual enzymatic activity found both in the muscle biopsy specimens and in
      the muscle cultures. There is strong suggestion that factors other than the
      amount of residual activity must be involved to determine the clinical
      manifestation of this disease.

PMID- 7805314
TI  - Myasthenia gravis and thymic Hodgkin's disease associated in one patient with
      familial lymphoproliferative disorders.
AB  - A 38-year-old man affected with generalized myasthenia gravis (MG) was submitted
      to thymectomy. At surgery thymic Hodgkin's disease (granulomatous thymoma) and an
      area of thymic hyperplasia were found. Subsequently, after treatment with
      anticholinesterase and corticosteroids, the patient achieved clinical remission.
      The development of MG in this patient could be related to the presence of thymic
      hyperplasia, rather than to the granulomatous thymoma. Family history revealed
      that a brother of the patient was affected by non-Hodgkin T-cell lymphoma. Human
      leukocyte antigens (HLA) were identical in the two affected siblings. The present
      report suggests a possible link between MG and lymphoproliferative disorders
      whose mechanism still needs to be clarified.

PMID- 7805315
TI  - Prominence of the C2 vertebra on SPECT. A normal variant.
AB  - Mild preferential focal uptake of Tc-99m HDP in the spinous process of C2 was
      identified with SPECT of the cervical spine performed in patients in whom the
      indication for bone scintigraphy was suspected of lesions in the limbs. Its
      presence in all 21 subjects indicates that such uptake is a normal finding.

PMID- 7805317
TI  - Increased Tc-99m MDP in multiple lumbar intervertebral disk spaces in Scheuermann
      disease without concomitant radiographic calcification or diskitis.
AB  - A radionuclide bone scan serendipitously revealed deposition of Tc-99m MDP in
      multiple lumbar intervertebral disk spaces in a 29-year-old man with extensive
      trauma to the left femur as a result of a motor vehicle accident. In the authors'
      experience, alcoholic liver disease or altered weight bearing secondary to prior
      trauma are not associated with intervertebral radiotracer uptake. Although it is
      possible that radiographically undetectable microcalcifications in the
      intervertebral disk spaces associated with degenerative changes, common in
      Scheuermann disease, account for this unusual finding, a literature search found
      that increased disk uptake had been reported only in two patients with
      Scheuermann disease who had concomitant active or healing diskitis. No other
      causes of increased disk uptake of Tc-99m MDP were found.

PMID- 7805318
TI  - Scintigraphic findings on examination of the multipartite patella.
AB  - Bipartite or multipartite patella occurs in approximately 2-3% of the general
      population. In the setting of trauma, this entity may be confused with a fracture
      of the patella. The mechanism of injury, clinical symptomatology, and plain film
      findings are often helpful in distinguishing the two possibilities. However,
      cases do occur in which a fracture cannot be confidently excluded. This case
      demonstrates how scintigraphy may provide further clarification in this
      diagnostic dilemma.

PMID- 7805316
TI  - Periprosthetic Clostridium difficile hip abscess imaged with In-111 WBCs.
AB  - During a prolonged hospital stay, left hip pain developed in a woman with sickle
      cell disease and bilateral hip prostheses. In-111 labeled WBC scintigraphy
      supplemented by Tc-99m SC bone marrow imaging demonstrated abnormal WBC
      accumulation surrounding the left greater trochanter. Results of surgical
      exploration showed an abscess involving the pseudocapsule, trochanteric bursa,
      and periprosthetic cement column. Cultures grew Clostridium difficile, an unusual
      pathogen in this site.

PMID- 7805319
TI  - Direct comparison of Tc-99m DTPA and Tc-99m HMPAO for evaluating brain death.
AB  - Portable cerebral perfusion studies provide a quick and accurate alternative to
      traditional confirmatory examinations (such as four-vessel angiography and
      electroencephalography) to determine brain death. The authors retrospectively
      analyzed 26 cerebral perfusion studies using both Tc-99m DTPA and Tc-99m HMPAO.
      The flow agents gave identical results. Additionally, the delayed-phase Tc-99m
      HMPAO images gave the same results for brain death (14 positive and 12 negative)
      as the flow images from either agent. Because the Tc-99m HMPAO delayed images can
      be used for diagnosis, many technical problems become less crucial. Unlike Tc-99m
      DTPA, Tc-99m HMPAO normally visualizes the gray matter of the cerebellum,
      midbrain, and medulla. These areas must be evaluated to ensure that they meet the
      strict criteria for brain death. These differences and the present study suggest
      that Tc-99m HMPAO is a superior agent for cerebral perfusion studies to determine
      brain death.

PMID- 7805320
TI  - Bilateral cerebral mediofrontal hypoactivity in Tc-99m HMPAO SPECT imaging.
AB  - Fifteen patients who had bilateral mediofrontal hypoactivity and 30 control
      subjects without this SPECT anomaly underwent Tc-99m HMPAO brain SPECT imaging.
      Bilateral mediofrontal hypoactivity was found in various neurologic disorders,
      including subcortical arteriosclerotic encephalopathy, lacunar state, chronic
      alcoholism, progressive nonvascular dementia, carbon monoxide poisoning, and
      diabetes mellitus. This SPECT abnormality was, however, specifically associated
      with three clinical signs: motor disabilities predominating in the lower limbs,
      urinary incontinence, and akinetic mutism.

PMID- 7805321
TI  - Incidental finding of herpes zoster infection by Tc-99m HMPAO.
AB  - Tc-99m HMPAO brain SPECT study incidentally demonstrated a large area of
      increased accumulation in the soft tissue of the face and fronto-parietal region
      of the head, corresponding to the distribution of the ophthalmic and maxillary
      branches of the trigeminal nerve, which had been infected by herpes zoster.

PMID- 7805322
TI  - Determination of the normal range of furosemide half-clearance times when using
      Tc-99m MAG3.
AB  - In radionuclide diuresis renography, furosemide half-clearance times have been
      established using Tc-99m DTPA but have not been verified when Tc-99m MAG3 is
      used. One hundred and six consecutive diuretic renograms using Tc-99m MAG3 for
      the evaluation of unilateral renal abnormalities were assessed. The furosemide
      half-clearance times of the normal kidneys were all less than 9.8 minutes, with a
      mean of 3.4 minutes. In 18 patients, the half-clearance times of the normal
      kidney were artificially prolonged because urine had drained before the
      administration of the diuretic. The normal furosemide half-clearance time values
      obtained using Tc-99m MAG3 were found to be similar to those established for Tc
      99m DTPA. Prolonged half-clearance times of Tc-99m MAG3 must be confirmed by
      visual evidence of obstruction.

PMID- 7805323
TI  - Renal artery embolism. Correlation with scintigraphic and radiographic findings.
AB  - The diagnosis of renal artery embolism should be considered in patients with
      cardiac disease who present with abdominal or flank pain in association with
      deteriorating renal function. Often the diagnosis is delayed or missed owing to
      the nonspecific, varied, and protean clinical manifestations. A case is presented
      of bilateral renal artery emboli, and initial and long-term scintigraphic and
      radiographic correlations are provided. Renal scintigraphy should be the initial
      study of choice. In addition, this procedure allows for sequential noninvasive
      evaluation of renal function.

PMID- 7805324
TI  - Tc-99m MAG3 renography in renal vein thrombosis secondary to Finnish-type
      congenital nephrotic syndrome.
AB  - Scintigraphic findings in renal vein thrombosis (RVT) have been well described on
      studies performed with Tc-99m DPTA, Tc-99m glucoheptonate, and I-131
      orthoiodohippurate. The authors could find no reports of RVT findings on Tc-99m
      mercaptoacetyltriglycine (MAG3) imaging. Tc-99m MAG3 renal scintigraphy in an
      infant with RVT because of Finnish-type congenital nephrotic syndrome is
      described. Correlative ultrasound and inferior vena cava venogram findings are
      presented.

PMID- 7805325
TI  - Scintigraphic diagnosis of peritoneo-pleural communication in the absence of
      ascites.
AB  - Pleural effusion in the presence of cirrhosis and ascites is well recognized.
      Peritoneal fluid is thought to enter the pleural cavity either because of
      overloaded lymphatics or a structural defect between the peritoneal and chest
      cavities. Pleural effusion rarely occurs in the absence of demonstrable ascites.
      This report describes the scintigraphic diagnosis of peritoneo-pleural
      communication in a patient with cryptogenic cirrhosis and pleural effusion
      without ascites.

PMID- 7805326
TI  - Clinical application of spontaneous red blood cell labeling with Tc-99m sodium
      pertechnetate.
AB  - Red blood cells (RBC) may be labeled with Tc-99m after Tc-99m sodium
      pertechnetate is injected in the presence of a reducing agent, such as stannous
      chloride. Thus, spontaneous RBC labeling with Tc-99m is expected to be seen in
      patients with a high plasma concentration of tin. Spontaneous RBC labeling with
      Tc-99m was obtained in a 73-year-old woman who was clinically diagnosed with tin
      intoxication and proved to have a high concentration of plasma tin. The RBC
      labeling rate was calculated as 96% with blood sampling. Spontaneous RBC labeling
      with Tc-99m is a very simple method for proving a high plasma tin concentration
      and is adaptable to clinical diagnosis.

PMID- 7805327
TI  - Tc-99m MIBI uptake in breast carcinoma and axillary lymph node metastases.
AB  - Two female patients with breast cancer and axillary lymph node metastases had Tc
      99m MIBI chest scintigraphy. The Tc-99m MIBI uptake in the primary breast cancer
      and metastatic lymph nodes were noted and discussed. The findings suggest that Tc
      99m MIBI chest scintigraphy for palpable breast masses and axillary lymph nodes
      is a helpful test in detecting malignant breast masses and metastatic lymph
      nodes.

PMID- 7805328
TI  - Scintigraphic appearance of albuterol-induced inhibition of hypoxic pulmonary
      vasoconstriction.
AB  - Alveolar hypoxia is known to result in localized pulmonary arterial
      vasoconstriction. As a consequence, blood is diverted from poorly ventilated
      alveoli, maintaining ventilation-perfusion (V/Q) matching and thereby reducing
      the deleterious effects on gas exchange. An incomplete alveolar hypoxic
      vasoconstrictive response can be easily demonstrated by radionuclide V/Q lung
      scanning. A case of albuterol-induced inhibition of hypoxic pulmonary
      vasoconstriction is described in a patient with steroid-dependent asthma. The
      utility of V/Q lung scanning as a simple, noninvasive test to detect this
      phenomenon in patients with primary airway disorders who deteriorate despite
      appropriate therapy is also briefly discussed.

PMID- 7805329
TI  - Exercise testing in patients with electrocardiographic evidence of left
      ventricular hypertrophy.
AB  - The purpose of this study was to determine the influence of left ventricular
      hypertrophy, based on electrocardiographic evidence, on the results of exercise
      thallium testing. Patients with electrocardiographic evidence of left ventricular
      hypertrophy (ECG-LVH) and suspected of having coronary artery disease underwent
      exercise thallium testing. Retrospective analysis of 107 consecutive patients
      with ECG-LVH showed transient myocardial perfusion defects (TMPD) in 12 (11%),
      indicative of myocardial ischemia; 12 (11%) had fixed myocardial perfusion
      defects (FMPD), indicative of probable myocardial infarction; 5 had TMPD plus
      FMPD (5%), and scan results for 78 were normal (73%). In patients with ECG-LVH,
      additional ST changes were observed in 76% and chest pain in 7% of patients with
      ECG-LVH. In a matched comparison group of 255 patients not prescreened for ECG
      LVH, TMPD was observed in 20%, FMPD in 16%, and TMPD plus FMPD in 26% of
      patients, and normal results were found in 38%. Electrocardiographic changes were
      found in 49% and chest pain in 20%. Hemodynamic responses to exercise were
      comparable between subgroups. Lung thallium uptake was quantified as the lung-to
      heart thallium activity ratio (L-H) on the immediate exercise anterior planar
      images. In controls, a significant increase in L-H was observed in patients with
      TMPD and TMPD plus FMPD. This was not observed in patients with ECG-LVH, possibly
      because of elevated thallium myocardial activity as a result of increased left
      ventricular mass. The conclusion is that patients with ECG-LVH often had normal
      perfusion scan results (73%) on exercise despite a high incidence of additional
      ECG changes (76%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7805330
TI  - Large reverse mismatch associated with pulmonary embolism.

PMID- 7805331
TI  - Uptake of In-111 GYK-DTPA B72.3 monoclonal antibody in metastatic squamous cell
      carcinoma.

PMID- 7805332
TI  - Schwannoma mimicking a metastatic breast lesion.

PMID- 7805333
TI  - In-111 DTPA cisternographic demonstration of magna cisterna magna.

PMID- 7805334
TI  - Diaphragmatic hernia producing a perfusion defect and diffuse pulmonary vascular
      hypoplasia on lung imaging.

PMID- 7805335
TI  - Detection of a carcinoid tumor by the radionuclide method.

PMID- 7805336
TI  - A huge osteophyte in the sacroiliac joint: appearance on bone SPECT.

PMID- 7805337
TI  - Brain perfusion scintigraphy with Tc-99m ethylcysteinate dimer for migraine
      accompagnee.

PMID- 7805338
TI  - Exercise-induced left ventricular dilatation.

PMID- 7805339
TI  - Hepatic diphosphonate accumulation secondary to malignant venous obstruction.

PMID- 7805340
TI  - Background--setting the stage for alternate-site laboratory testing.
AB  - Market forces and service demands are driving a segment of laboratory testing
      away from centralized laboratories and closer to the patient's bedside. Placed
      into a historical perspective, this should be neither surprising nor distressing.
      Terminology is being clarified and professional societies are beginning to take
      the lead in molding these testing strategies into appropriate tools for advancing
      excellent patient care.

PMID- 7805341
TI  - The advance of technology as a prelude to the laboratory of the twenty-first
      century.
AB  - Technological changes in the clinical laboratory are usually driven by the goal
      of patient care optimization. In the last decade, the trend appeared to be
      directed at clinical laboratory decentralization. A new generation of analytical
      instruments, the biosensors, is redirecting laboratory testing closer to the
      patient, at the bedside, in the physician's office, and by the patient at home.
      These miniaturized biosensors are easy to operate, require small specimen size,
      and provide reliable results with rapid TAT. Thus far, bedside testing using
      biosensor technology appears to offer unique opportunities for earlier
      availability of clinical laboratory data, decision making, and more specific
      diagnosis, and faster and more frequent monitoring; these may translate into
      improved patient care and reduced hospital costs. It is likely that this trend
      will continue into the twenty-first century. Electrochemical sensors (e.g., for
      electrolytes, glucose, urea, and hematocrit) and pulse oximetry, having gained
      clinical acceptance, will probably be the leading instrumentation for bedside
      testing. Continuous monitoring either by near-infrared sensing technology or with
      an implantable sensor is valuable in the care of the critically ill patient.
      Acceptance for clinical use will depend on complete data integration and a
      favorable cost-benefit ratio.

PMID- 7805342
TI  - Testing at the patient's bedside.
AB  - Performing laboratory tests at the patient's bedside has become a popular
      component of care, primarily because of the immediate availability of test
      results. Bedside glucose monitoring programs have been the prototype for bedside
      testing and have provided the most experience in this area. Studies of bedside
      glucose testing have shown that in order to obtain reliably accurate results,
      there must be a well-designed and well-implemented quality assurance program,
      which should involve laboratory professionals. However, medical necessity, cost,
      and alternatives should be thoroughly considered before beginning a bedside
      testing program, as well as the commitment to a strong quality assurance program.

PMID- 7805343
TI  - Consolidating ancillary testing in multihospital systems.
AB  - This article introduces a new initiative that allows medical centers to establish
      uniformity and quality management of laboratory diagnostic testing performed in
      on-site and outreach locations for hospitalized inpatients and ambulatory care
      patients. This article also reviews the requirements of the Clinical Laboratory
      Improvement Amendments of 1988 (CLIA '88) and how they affect ancillary testing
      sites.

PMID- 7805344
TI  - Laboratories in patient-centered units.
AB  - As part of a hospital pilot project evaluating decentralized patient-focused
      care, a new laboratory model was studied. Cross-trained personnel (nurses,
      medical technologists, radiology technologists, and respiratory therapists)
      performed high-volume, automated laboratory tests in a unit-based laboratory as
      part of their overall patient care duties. Testing performed in the patient
      centered unit laboratory, in general, was comparable in quality to that reported
      by the hospital's central laboratory.

PMID- 7805345
TI  - Quality control and quality management of alternate-site testing.
AB  - Quality is an important attribute of clinical laboratory results; however,
      methods for defining acceptable quality may not be entirely agreed upon. In
      addition, confusion over quality is added when laboratory testing is moved to
      alternate sites. As quality parameters are designed for novel laboratory delivery
      systems, it will be best to use novel approaches that build on already well
      defined principles of laboratory quality management.

PMID- 7805346
TI  - Multimedia communications networks. Patient care through interactive point-of
      care testing.
AB  - This decade will see a historical convergence of technologic and socioeconomic
      events that will merge interactive multimedia communications with longitudinal
      participatory health care systems. Diagnostic testing will extend from the home
      to the most sophisticated acute care settings. Point-of-care testing networks
      will resemble modern electrical utility power grids with workload distributed to
      optimize test turnaround time and economic effectiveness. Throughout the network,
      clinical and managerial information will be accessible as needed at all points of
      use. The networks will become "physician extenders" by allowing broad interactive
      geographic and mobile accessibility to clinical information in a context that
      maintains patient confidentiality and data security.

PMID- 7805347
TI  - Alternate-site testing. Consider the analyst.
AB  - The ability to perform accurate and precise testing in sites outside the main
      clinical laboratory is more dependent on the quality of the individual performing
      the alternate-site testing (AST) than on any other factor. Most of these
      individuals have little or no laboratory training or experience. The central
      laboratory must take responsibility for training AST analysts, monitoring their
      performance (testing, QC, PT, and QA), and certifying their competence. Regular
      retraining and recertification must be performed.

PMID- 7805348
TI  - Regulatory and accreditation implications of alternate-site laboratory testing.
AB  - The expectations of voluntary accrediting organizations and federal regulatory
      agencies with regard to laboratory performance standards that must be satisfied
      for alternate-site testing are described. The guidelines and requirements for
      accreditation of laboratory programs by the College of American Pathologists and
      the Joint Commission on Accreditation of Healthcare Organizations are
      demonstrated, along with applicable commentary.

PMID- 7805349
TI  - Decentralized testing in the 1990s. A survey of United States hospitals.
AB  - Laboratory testing is increasingly moving out of the central laboratory and into
      other areas of the hospital. Many factors are driving this trend, but most
      revolve around the desire for prompt, medical decision making guided by quick,
      convenient on-site or decentralized testing using emerging new technologies. This
      article reviews a 1993 independent survey on decentralized testing throughout US
      hospitals. It discusses and quantifies various aspects of decentralized testing
      technology as well as identifies general trends.

PMID- 7805350
TI  - Lead poisoning--Part II. Effects and assay.
AB  - This second part of the review article compiles currently available information
      on the effects of lead poisoning. Also examined are the available options for
      assay, the procedures for collection of samples, and the available methods for
      the estimation of lead in the collected samples.

PMID- 7805351
TI  - The relationship between cognition and action: performance of children 3 1/2-7
      years old on a Stroop-like day-night test.
AB  - One hundred and sixty children 3 1/2-7 years of age (10 M, 10 F at each 6-month
      interval) were tested on a task that requires inhibitory control of action plus
      learning and remembering two rules. They were asked to say "day" whenever a black
      card with the moon and stars appeared and to say "night" when shown a white card
      with a bright sun. Children < 5 years had great difficulty. They started out
      performing well, but could not sustain this over the course of the 16-trial
      session. Response latency decreased from 3 1/2 to 4 1/2 years. Children < 4 1/2
      years performed well when they took very long to respond. To test whether the
      requirement to learn and remember two rules alone was sufficient to cause
      children difficulty, 80 children 3 1/2-5 years old were tested on a control
      version of the task ("say 'day' to one abstract design and 'night' to another").
      Even the youngest children performed at a high level. We conclude that the
      requirement to learn and remember two rules is not in itself sufficient to
      account for the poor performance of the younger children in the experimental
      condition.

PMID- 7805352
TI  - Does sentential prosody help infants organize and remember speech information?
AB  - Theories that propose a mapping between prosodic and syntactic structures require
      that prosodic units in fluent speech be perceptually salient for infants.
      Although previous studies have demonstrated that infants are sensitive to
      prosodic markers of syntactic units, they do not show that prosodic information
      really has an impact on how infants encode the speech they hear. Two experiments
      were conducted to examine whether infants as young as 2 months old might actually
      use the prosody afforded by sentences to organize and remember spoken
      information. The results suggest that infants better remember the phonetic
      properties of (1) words that are prosodically linked together within a single
      clause as opposed to individual items in a list (Experiment 1); and (2) words
      that are prosodically linked within a single clausal unit as opposed to spanning
      two contiguous fragments (Experiment 2). Taken together, the evidence from both
      experiments suggests that the prosodic organization of speech into clausal units
      enhances infants' memory for spoken information. These findings are discussed
      with regard to their implications for theories of language acquisition.

PMID- 7805353
TI  - The sequential curing effect in speech production.
AB  - How are the sounds of words represented in plans for speech production? In
      Experiment 1, subjects produced sequences of four CVCs as many times as possible
      in 8s. We varied the number of repetitions of the initial consonant, vowel, final
      consonant, CV, rhyme, and whole CVC each sequence required, and measured
      subjects' speaking rate. Subjects produced more CVCs when the final consonant or
      whole word was repeated, but were slowed when only initial sounds or CVs were
      repeated. Two other experiments replicate the location-based effects and extended
      them to bisyllabic words. We attribute the locational effects to competition
      between words that are formally similar, and specifically, to competition between
      discrepant phonemes in the two words to occupy a particular wordframe position.
      The fact that only discrepant initial, but not final sounds slow production
      suggests that phonemes are activated sequentially, from left to right.

PMID- 7805354
TI  - Comparative evaluation of the E test for susceptibility testing of Nocardia
      species.
AB  - The E Test (PDM Epsilometer; AB Biodisk, Solna, Sweden) was compared with
      microbroth dilution and disk diffusion for antimicrobial susceptibility testing
      of Nocardia as a collaborative study by two geographically separate laboratories.
      A total of 52 clinical isolates and five species of Nocardia were used in this
      comparative evaluation. Susceptibility testing was performed with Mueller-Hinton
      media and eight antimicrobial agents. Growth of the test strains with Mueller
      Hinton medium was generally satisfactory, with the majority of isolates producing
      adequate growth within 24-36 h. Growth inhibition ellipses were generally well
      delineated and uniform for most drugs, and the points of intersection with the E
      Test strip were generally easy to determine. An inoculum size of approximately
      2.0 x 10(7) CFU/ml was optimal for performance of the E Test method with the
      Nocardiae. Comparison of E Test and microbroth dilution MICs revealed 89.4%
      agreement for all drugs within +/- 1 log2 dilution. Using NCCLS interpretive
      criteria for susceptible and resistant results, complete agreement between E Test
      and disk diffusion results was 93.3%, and between E Test and microbroth dilution
      results was 96.2%. Interpretive category errors occurred at rates of 18.2% (risk
      corrected), 0, and 4.1% for very major, major, and minor errors, respectively,
      when E Test results were compared with disk diffusion results, and 0, 0, and
      3.8%, respectively, when E Test was compared with microbroth dilution. Inter- and
      intra-laboratory reproducibility, within +/- 1 log2 dilution for all drugs, was
      95% and 98%, respectively. Results from this study suggest that E Test may be
      suited for use as an alternative method for antimicrobial susceptibility testing
      of Nocardia species.

PMID- 7805355
TI  - Multicenter evaluation of the in vitro activity of piperacillin-tazobactam
      compared with eleven selected beta-lactam antibiotics and ciprofloxacin against
      more than 42,000 aerobic gram-positive and gram-negative bacteria. In Vitro
      Susceptibility Surveillance Group.
AB  - The in vitro activities of piperacillin-tazobactam, 11 other beta-lactam
      antibiotics, and ciprofloxacin were evaluated in a large multicenter study. A
      total of 42,208 organisms, collected from 79 listed medical centers and large
      community hospitals, were tested using the National Committee for Clinical
      Laboratory Standards broth microdilution procedure. Imipenem (94.7% inhibition),
      ciprofloxacin (93.8%), and ceftazidime (90.8%) were the most active antibiotics
      against 31,426 Gram-negative bacilli. Piperacillin-tazobactam (88.8%) and
      ticarcillin-clavulanate (86.4%) were the most active combination antibiotics
      against these organisms. Ampicillin-sulbactam (97.8%), piperacillin-tazobactam
      (96.4%), and imipenem (96.9%) were the most active antibiotics against 10,782
      Gram-positive cocci. Overall, the most active antibiotics against all organisms
      tested were imipenem (95.2%), ciprofloxacin (91.0%), and piperacillin-tazobactam
      (90.8%).

PMID- 7805356
TI  - Cefetamet pivoxil in the treatment of uncomplicated gonorrhea.
AB  - We studied the efficacy and safety of cefetamet pivoxil (CAT), an oral
      aminothiazolyl cephalosporin, in a series of open, comparative multicenter
      studies in 207 women (four study centers) with uncomplicated gonorrhea, and
      summarized and pooled the results with those of earlier open dose-finding trials
      (360 men; six study centers). We compared single-dose treatment regimen of CAT-
      over the range of 400-1500 mg--with spectinomycin, thiamphenicol, ampicillin, or
      amoxicillin plus probenecid. The overall cure rates were 100% in 88 women treated
      with 1500 mg CAT and in 137 men treated with 1200 or 1500 mg CAT, 98% (114 of 116
      men) in those treated with 800 or 1000 mg CAT, and 93% (42 of 45 men) in those
      treated with 400 or 500 mg CAT; the composite cure rate of the comparators was
      97%. The tolerability of CAT (n = 428) compared favorably (1.8% adverse events)
      with that of the standard drugs (n = 139) (4.3% adverse events). Single-dose
      treatment with 1500 mg CAT is effective and safe in adults with uncomplicated
      gonorrhea.

PMID- 7805357
TI  - In vitro activity of grepafloxacin (OPC-17116) against anaerobic bacteria.
AB  - In vitro activity of the quinolone grepafloxacin (OPC-17116) was compared with
      that of ciprofloxacin, fleroxacin, clindamycin, imipenem, and metronidazole by
      using the NCCLS-approved Brucella-base-laked blood agar dilution method and
      breakpoints, when available. Clindamycin, metronidazole, and imipenem inhibited >
      or = 98% of Bacteroides fragilis at the breakpoint; grepafloxacin, ciprofloxacin,
      and fleroxacin inhibited 83%, 6%, and 0, respectively, at 2 micrograms/ml.
      Grepafloxacin inhibited 39% of other B. fragilis group species isolated (80) at
      breakpoint (< or = 2 micrograms/ml) compared with 100% for metronidazole and
      imipenem, 83% for clindamycin, 6% for ciprofloxacin, and 1% for fleroxacin.
      Grepafloxacin demonstrated substantially better activity against B. fragilis than
      did ciprofloxacin or fleroxacin; overall activity against anaerobes was
      marginally better than that of ciprofloxacin or fleroxacin.

PMID- 7805358
TI  - Bacteriologic characteristics and antimicrobial susceptibility of 70 clinically
      significant isolates of Streptococcus milleri group.
AB  - The phenotypical characteristics of 70 clinical isolates of Streptococcus milleri
      group were analyzed. Association of the three species with particular sites of
      isolation could not be demonstrated in all cases, but S. anginosus strains
      predominated in abdominal area, while S. intermedius was isolated mainly in
      hepatic abscesses. Penicillin G and other beta-lactams showed good in vitro
      activity against these streptococci, whereas > 10% exhibited resistance to
      erythromycin and clindamycin. Resistance to tetracycline reached almost 40%. All
      of the isolates were uniformly susceptible to vancomycin, chloramphenicol, and
      trimethoprim.

PMID- 7805359
TI  - Antifungal activity of a new triazole, D0870, compared with four other antifungal
      agents tested against clinical isolates of Candida and Torulopsis glabrata.
AB  - D0870 is a new triazole agent with potent, broad-spectrum antifungal activity. We
      investigated the in vitro activity of D0870, fluconazole, itraconazole,
      amphotericin B, and 5-fluorocytosine (5FC) against 319 clinical isolates of
      Candida spp. and Torulopsis glabrata. In vitro susceptibility testing was
      performed using a microdilution broth method performed according to NCCLS
      guidelines. D0870 was very active (MIC90 of 0.12 microgram/ml and 0.5
      microgram/ml at 24 and 48 h incubation, respectively) against all of the yeast
      isolates. D0870 was 2- to 32-fold more active than amphotericin B and 2- to 8500
      fold more active than 5FC. By comparison with the other triazoles, D0870 was
      generally 2- to 16-fold more active than itraconazole and > or = 16-fold more
      active than fluconazole. More than half (53%) of C. albicans isolates with
      elevated fluconazole and itraconazole MICs (> or = 128 micrograms/ml and > 8.0
      micrograms/ml, respectively) were inhibited by < or = 1.0 microgram/ml of D0870.
      Based on these studies, D0870 has promising antifungal activity and warrants
      further in vitro and in vivo investigation.

PMID- 7805360
TI  - Mycobacterial identification by computer-aided gas-liquid chromatography.
AB  - The suitability of the Microbial Identification System (MIS) marketed by
      Microbial ID (Newark, DE, USA) for routine diagnosis of clinically important
      mycobacteria was investigated and assessed. Cellular fatty acids were extracted
      from 1077 stock and recent clinical isolates. They were analyzed using a gas
      liquid chromatograph combined with MIS software. The MIS system finally
      identifies the isolates by comparing their fatty-acid compositions with a
      standard library for mycobacteria. As the library search usually results in more
      than one possible match, suitable identification criteria were determined. The
      stricter these criteria are, the more the percentage of false-positive
      identifications can be reduced, but at the cost of more cases that remain
      undecided and require additional analysis. Under conditions similarity index (SI)
      SI1 > or = 0.4 and SI1-SI2 > or = 0.1, 63% of all isolates were correctly and 6%
      incorrectly identified.

PMID- 7805361
TI  - Evaluation of the Merifluor immunofluorescent assay for the detection of
      Cryptosporidium and Giardia in sodium acetate formalin-fixed stools.
AB  - The Merifluor Cryptosporidium/Giardia direct immunofluorescent assay (MFDFA) was
      used for the blinded detection of Cryptosporidium and Giardia in 100 previously
      tested sodium acetate formalin (SAF)-preserved fecal specimens. Examination for
      ova and parasites by formalin-ether concentration followed by iron-hematoxylin
      and Kinyon staining had demonstrated Cryptosporidium (n = 32), Giardia (n = 20)
      and both Giardia and Cryptosporidium (n = 5). The MFDFA detected one additional
      specimen with Cryptosporidium and another with Giardia and was rapid, accurate,
      and simple to perform.

PMID- 7805363
TI  - Health care delivery for the elderly--reform or revolution?

PMID- 7805362
TI  - Interpretive criteria for susceptibility tests with DU-6859a and FK-037 tested
      against Haemophilus influenzae and Neisseria gonorrhoeae.
AB  - Preliminary susceptibility testing interpretive criteria were determined for two
      investigational drugs, DU-6859a and FK-037, when tested against Haemophilus
      influenzae and Neisseria gonorrhoeae strains. National Committee for Clinical
      Laboratory Standards (NCCLS) methods with the Haemophilus Test Medium and GC agar
      base were utilized, and the study design conformed to the NCCLS M23-A guidelines.
      The proposed H. influenzae susceptibility testing criteria were for DU-6859a
      susceptible at < or = 1 microgram/ml (5-micrograms disk zone diameter correlate,
      > or = 19 mm) or < or = 2 micrograms/ml (disk zone diameter correlate, > or = 16
      mm) and for FK-037 susceptible at < or = 2 micrograms/ml (30-micrograms disk zone
      diameter correlate, > or = 19 mm). No other susceptibility categories were
      proposed. The gonococcal susceptibility testing criteria were for DU-6859a
      susceptible at < or = 0.12 microgram/ml (disk zone diameter correlate, > or = 34
      mm) and for FK-037 susceptible at < or = 0.5 microgram/ml (disk zone diameter
      correlate, > or = 30 mm) and resistant at > 1 microgram/ml (disk zone diameter
      correlate, < or = 26 mm). No resistant criterion was proposed for N. gonorrhoeae
      tests with DU-6859a. No interpretive discrepancies were observed between methods
      using these proposed testing criteria.

PMID- 7805364
TI  - Dietary factors and kidney stone formation.
AB  - Kidney stone disease is a substantial health problem associated with significant
      pain and suffering, as well as economic costs. Over $2 billion were spent in 1986
      on stone disease, the majority on treatment of existing stones and only a small
      percentage on prevention. Clearly, efforts to prevent or at least reduce the
      likelihood of developing a kidney stone would be an important component of the
      care of patients at risk. In particular, modifiable dietary factors appear to
      play an important role in the formation of calcium oxalate stones--the type of
      stone formed in the vast majority of cases. Once secondary causes of stone
      formation, such as hyperparathyroidism and renal tubular acidosis, are excluded,
      dietary counselling is a prudent and effective element of the therapeutic regimen
      and kidney stone prevention program. Specifically, for individuals who have a
      history of a calcium-containing kidney stone, important dietary recommendations
      should include the following: Achieve adequate fluid intake to produce at least 2
      liters of urine per day. Avoid calcium restriction (except in the rare instances
      of excessive intake of greater than several grams per day). It is recommended a
      dietary intake of elemental calcium of at least 800 mg/day (the current RDA for
      adults) to prevent a negative calcium balance, bone mineral loss, and increased
      intestinal absorption of oxalate. At present, there is no evidence to support the
      belief that calcium restriction is beneficial and current data suggest that it
      may in fact be harmful.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7805365
TI  - Review of dietary therapy for rheumatoid arthritis.

PMID- 7805366
TI  - The nutritional management of coronary artery disease.

PMID- 7805367
TI  - Essential and trans fatty acid metabolism in health and disease.

PMID- 7805368
TI  - The effects of dietary factors on blood pressure.

PMID- 7805369
TI  - Cholesterol-lowering and psychological well-being.

PMID- 7805370
TI  - Nutritional consequences of intestinal bacterial overgrowth.
AB  - The bacterial overgrowth syndrome occurs when there are alterations in intestinal
      anatomy, gastrointestinal motility, or a lack of gastric acid secretion.
      Clinically, patients present with nonspecific gastrointestinal symptoms that
      include abdominal pain, bloating, excessive gas production, diarrhea, weight
      loss, and malabsorption. The nutritional consequences of intestinal bacterial
      overgrowth include vitamin deficiencies, fat malabsorption, and malnutrition. The
      diagnosis requires a high index of clinical suspicion and can be established by
      specialized testing, such as the 1-gram 14C-xylose breath test. The goal of
      treatment is eradication of the bacterial overgrowth (usually with antibiotics)
      and the correction of nutritional deficiencies.

PMID- 7805371
TI  - Clinical comparison of monophasic oral contraceptive preparations of
      gestodene/ethinyl estradiol and desogestrel/ethinyl estradiol. Latin American
      Oral Contraceptive Study Group.
AB  - The efficacy, cycle control, subjective complaints, and safety of monophasic
      preparations of the oral contraceptives containing gestodene 75 mcg plus ethinyl
      estradiol 30 mcg versus desogestrel 150 mcg plus ethinyl estradiol 30 mcg were
      compared in a 6-cycle, open-label, parallel, randomized, multicenter phase IV
      clinical study in Latin America. Of a total of 176 women in each group, 163 in
      the gestodene group and 160 in the desogestrel group completed 6 cycles,
      providing data for 1,015 and 1,006 cycles, respectively. Subject compliance was
      excellent; pills were missed during only 6.9% of the cycles in each group. No
      woman became pregnant during the study. Gestodene group exhibited significantly
      better cycle control as evidenced by the lower incidence of breakthrough bleeding
      and spotting. Spotting in some cycles was reported by 11.9% of women taking the
      gestodene-combination compared with 21% of women taking the desogestrel
      combination. Based on number of women, 86.4% of the gestodene group reported all
      cycles were normal (no BTB) compared with 76.7% of the desogestrel group. Also,
      the women in the gestodene group reported a significantly lower incidence of
      nuisance side effects during treatment cycles. No amenorrhea was observed for
      either group. There were no clinically significant differences between groups
      with respect to body weight, blood pressure, or laboratory evaluations. Seven
      women withdrew from the gestodene group and 8 women withdrew from the desogestrel
      group because of adverse reactions. The results of this study indicate that,
      although both OCs provided effective contraception, in comparison to the
      desogestrel-combination, the gestodene-containing OC is associated with better
      cycle control, less bleeding, and fewer subjective complaints.

PMID- 7805372
TI  - Improved utilization of spacing methods--intrauterine devices (IUDs) and low-dose
      combined oral contraceptives (OCs)--through re-orientation training for improving
      quality of services. Indian Council of Medical Research Task Force on IUD and
      Hormonal Contraceptives.
AB  - A multicentre study was conducted by the Indian Council of Medical Research
      (ICMR) for improving the utilization of intrauterine devices (IUDs) and oral
      contraceptives (OCs) at the Post Partum Centres (PPCs) run by District/State
      Health Authorities. The ICMR's network of Human Reproduction Research Centres
      (HRRCs) had the technical responsibility for providing re-orientation training to
      health functionaries (medical and paramedical) of the PPCs for better quality of
      services and follow-up care for IUD and OC users. The uniform training module was
      utilized by all HRRCs which specifically assured for improving the
      counselling/motivational skills as well as screening procedures and management of
      side-effects and follow-up care by the health functionaries. A total of 4,808 IUD
      acceptors (2,446 of CuT 200 and 2,362 of CuT 380A) were observed for 84,070 women
      months of use (42,433 and 41,637 months for CuT 200 and CuT 380A, respectively).
      The cumulative method failure rate at the end of two years was 0.7 per 100 users
      with CuT 200 and 0.3 per 100 users with CuT 380A. No perforations were reported
      with either types of the CuT devices. The reasons for discontinuations, like
      pain/bleeding and pelvic infections, were similar with both types of devices. The
      continuation rates with either CuT 200 or CuT 380A were around 89 and 76 per 100
      users at the end of first year and second year of use, respectively, and were
      comparable. These observations at the post partum centres were similar to those
      observed earlier by the ICMR in phase III controlled clinical study. A total of
      1,961 women were enrolled in the low-dose combined oral contraceptive (OC) group
      and were followed for 26,462 women-months of use. Two subjects reported pregnancy
      during regular use of pill, giving the method failure rate of 0.2 per 100 users
      at 2 years. The continuation rates of OC users were 58 and 37 per 100 users at
      the end of first year and second year, respectively. The major reasons for
      discontinuations were lost to follow-up, desire for pregnancy and other personal
      reasons. In spite of all efforts made by PPC staff as well as HRRCs to do follow
      up, the lost to follow-up at two years was around 20 percent for IUD and 31
      percent for oral pill users. These data suggest that while the re-orientation
      training package improved the quality of care resulting in higher continuation
      rates of IUDs and OCs at PPCs, the issue of follow-up care still requires further
      improvement in the National Programme.

PMID- 7805373
TI  - Contraceptive application of the Bioself fertility indicator.
AB  - The Bioself fertility indicator is a hand-held electronic device that combines
      the basal body temperature and calendar methods for planning or preventing
      pregnancy. A study was undertaken in three centers in the province of Quebec,
      Canada, to evaluate the Bioself device as a contraceptive aid. Eighty-three women
      were recruited; they accumulated 745 cycles of use. Six unplanned pregnancies
      occurred from unprotected intercourse during the fertile phase of the cycle, as
      indicated by the Bioself device. The pregnancy rate was 9.02 per 100 women-years
      and the one-year discontinuation rate was 32.5%. The low pregnancy rate is
      attributed to the women's experience in natural family planning, reinforced, in
      51% of the cycles, by protection from additional barrier methods. It was
      concluded that the Bioself device is an effective contraceptive aid for couples
      who are aware of the pros and cons of natural family planning and desire a
      noninvasive means of contraception.

PMID- 7805374
TI  - The influence of midtrimester termination of pregnancy on subsequent fertility:
      four to five years follow-up.
AB  - A four to five years follow-up upon subsequent fertility was performed on 46
      women who underwent a midtrimester termination of pregnancy. Thirty out of 31
      (96.8%) women who wanted to conceive became pregnant. Of those, term delivery
      rate was 73.3%. Only one woman who desired to conceive could not become pregnant.
      Her infertility workup revealed bilateral occlusion of tubes. We conclude that
      termination of pregnancy in midtrimester possibly has little, if any, impact upon
      subsequent fertility.

PMID- 7805375
TI  - Quinacrine and copper, compounds with anticonceptive and antineoplastic activity.
AB  - Changes in the evolution of a malignant transplantable tumor in mice to whom
      quinacrine, copper and zinc were supplied in drinking water are reported. Male AJ
      mice were inoculated in the right thigh with 1,000,000 TA3 or TA3 MTXR tumoral
      cells. Three experiments were designed with different types of tumors and
      different schedules of quinacrine and cations administered in drinking water. The
      animals that received quinacrine or quinacrine plus copper in drinking water had
      significantly smaller tumors, and some groups had a high rate of complete tumor
      regression (up to 60%). Quinacrine and copper have synergistic antineoplastic
      activity. Zinc salts do not improve the antitumoral effect of quinacrine. The
      relevant fact of this experiment lies in the fact that a large number of women
      using IUDs with copper could occasionally be treated with quinacrine.

PMID- 7805376
TI  - An epidemiological study on the relationship of ectopic pregnancy and the use of
      contraceptives in Beijing--the incidence of ectopic pregnancy in the Beijing
      area. Beijing Collaborating Study Group for Ectopic Pregnancy.
AB  - The incidence of ectopic pregnancy (EP) was studied through a 3-level monitoring
      network of maternal and child health care (MCH) in the entire Beijing area,
      including 82 hospitals, 19 MCH centers and 2 institutes for family planning. A
      total of 1,420 cases of EP were collected in a sample of 2.7 million women of
      reproductive age (15-49) during a one-year period from January 1 to December 31,
      1990. The cases were confirmed by pathological examination or laparoscopy. In
      addition, epidemiological surveillance method was used. The results showed that
      the overall incidence of EP was 0.52 per thousand women of reproductive age (W =
      Women of reproductive age (15-49)) in the Beijing area, 0.6/1000W in the urban
      districts and 0.41/1000 in the rural area; 0.67/1000W married women, and
      0.05/1000W in the unmarried. For married women, 0.54/1000W for those women using
      various contraceptive measures and 1.80/1000W for women using no contraceptives.
      The incidence of EP varies with different contraceptive methods. Female
      sterilization had the lowest incidence (0.18/1000W) and natural contraceptive
      measures (rhythm or withdrawal method) had the highest (2.43/1000W). It was
      0.65/1000W in IUD users, 0.21/1000W in OC users and 0.57/1000W in couples using
      condoms or spermicides.

PMID- 7805377
TI  - The effect of husband counseling on NORPLANT contraceptive acceptability in
      Bangladesh.
AB  - A pilot study of the effect of husband counseling on NORPLANT contraceptive
      acceptability was conducted at four family planning clinics in Bangladesh. The
      study objectives were to compare discontinuation rates and user satisfaction
      among acceptors whose husbands received counseling about the method versus those
      who did not. Of a total 617 subjects enrolled in the study which began in 1988,
      about two-thirds (408) of the husbands were counseled at admission or at the one
      month follow-up visit while the remainder of the husbands (209) were not
      counseled. Follow-up visits were scheduled at one and six months after NORPLANT
      implants insertion, and every six months thereafter until the close of the study
      in 1991. Some evidence was found that counseling husbands of NORPLANT implants
      acceptors may reduce discontinuation rates. At the end of 36 months, a difference
      of 10 percentage points in total discontinuation rates was observed between the
      husband-counseled group (32 per 100 women) and the husband-not-counseled group
      (42 per 100 women). The husband counseling had the most impact at clinics with
      higher discontinuation rates. Based on Cox's proportional hazards regression
      model results, the hazard for discontinuation among the acceptors in the husband
      not-counseled group. Satisfaction with NORPLANT implants did not differ between
      the two groups. Although these results are not striking, they do suggest a
      potential positive effect of husband counseling on NORPLANT contraceptive accept
      ability. In future studies, the counseling of husbands should be more intensive
      and standardized.

PMID- 7805379
TI  - Post-coital contraceptive activity of crude extracts of Sri Lankan marine red
      algae.
AB  - This study investigates the potential of marine red algae as a source for post
      coital contraceptive agents using three varieties: Gracilaria corticata,
      Gelidiella acerosa and Jania sp. Methanol: methylene chloride (1:1) extracts of
      these red algae were made and were orally administered (500 or 1000 mg/kg/day) to
      female rats from day 1 to day 7 of pregnancy. The higher dose of Gracilaria
      corticata and both doses of Gelidiella acerosa extracts produced significant post
      coital contraceptive activities without any marked side effects. Furthermore, the
      post-coital contraceptive activity of the latter extract was dose-dependent. On
      the other hand, extract made from Jania sp. had no significant post-coital
      contraceptive action. The post-coital contraceptive activity of Gracilaria
      corticata was due to enhanced pre-implantation loss and of Gelidiella acerosa was
      due to elevated post-implantation loss. These findings indicate that marine red
      algae is a useful source to be harvested for potential post-coital contraceptive
      drugs.

PMID- 7805378
TI  - The progestin ST 1435--rapid metabolism in man.
AB  - Parenterally administered ST 1435 (Nestorone) is highly potent for contraception,
      and ovulation can be inhibited with very low serum levels of ST 1435. Orally
      administered ST 1435 is ineffective in various laboratory animals, presumably due
      to extensive first-pass metabolism. Thus, ST 1435 has been proposed for
      lactational contraception, to be metabolized by the suckling infant. We have
      studied the metabolism of ST 1435 in female volunteers following oral (10 mg),
      intravenous (iv) (0.1 mg) and transdermal (4.5-9.0 mg) routes of ST 1435
      administration. Preliminary studies using rats were performed to develop the
      methodology of high performance-liquid chromatography (HPLC) fractionation and ST
      1435-RIA detection. Rat portal serum revealed 4 distinct peaks of immunoreactive
      material with the retention times (Rt's) of 7.5, 10, 14.5 and 17.5 min (ST 1435 =
      10 min). In systemic serum, only the peak with the Rt of 7.5 min could be
      detected. Therefore, orally administered ST 1435 is very effectively metabolized
      by the rat liver; this also explains the previously observed lack of biological
      effects of oral ST 1435. Following oral administration of ST 1435 to two women,
      the Rt of the major peak was 10 min. The magnitude of the ST 1435 peak decreased
      rapidly, and at 24h following ingestion, no ST 1435 could be detected by this
      method. The t1/2 of ST 1435 was approximately 1-2h. In addition, two minor peaks
      with Rt's of 4.5 and 16 min could be detected with the ST 1435 RIA at 1-4h
      following oral ingestion. Competitive receptor binding assays using the human
      uterine progesterone receptors (hPR) revealed that the ST 1435 fraction exhibits
      strong binding affinity towards the hPR; thus, in the human, a small fraction of
      biologically active ST 1435 seems to escape from the first-pass metabolism
      following oral intake. Following iv and transdermal administration of ST 1435,
      the only detectable peak with ST 1435-RIA was that of ST 1435. Similar magnitude
      of the ST 1435 peaks following oral administration of 10 mg and iv administration
      of 0.1 mg indicated that the bioavailability of ST 1435 is low. These data seem
      to confirm the suspicion that orally administered ST 1435 is also rapidly
      metabolized in the human, therefore encouraging further evaluation of ST 1435
      during lactation. However, the rapid metabolism seen after oral intake can be
      successfully circumvented by sustained parenteral administration of ST 1435.

PMID- 7805380
TI  - Implicit verbal memory in Alzheimer's disease.
AB  - Word stem completion and word identification were used in two repetition priming
      experiments to evaluate the implicit memory performance of Alzheimer's disease
      (AD) patients. This issue was also approached using various meta-analyses
      combining and contrasting previously reported data. While the experimental
      results suggested that AD patients present preserved repetition priming in both
      tasks, the meta-analytic approach showed an impairment in stem completion in
      comparison to word identification. Converging evidence cautiously suggested to
      accept the results of the meta-analysis. The above dissociation has been
      interpreted as showing differences in the specific contribution of data- and
      conceptually-driven processes in the two implicit tasks. A further meta-analysis
      on the effect of reduced perceptual availability of the study material on the
      same two tasks indicated that this variable affected repetition priming in word
      identification more heavily than in stem completion. The impact of such a
      dissociation on theories of implicit memory is discussed.

PMID- 7805381
TI  - Evidence of covert recognition in a prosopagnosic patient.
AB  - This is a case-study of a patient (ET) who suffers from prosopagnosia, in the
      context of impairment to cognitive functions, following traumatic brain injury.
      Despite severe perceptual difficulties in tests involving non-face stimuli and
      matching unfamiliar faces, ET showed evidence of "covert" recognition of familiar
      faces in a number of tasks. Although densely prosopagnosic, she performed at
      normal levels in word and object recognition tasks, and is unimpaired in her
      ability to recognise names of celebrities. She performed at the same level as
      controls in her ability to make a forced-choice of the correct name for a famous
      face, even though it evoked no feeling of familiarity for her. She performed at
      chance in a forced-choice face familiarity decision task, but showed evidence of
      covert recognition in a "true" versus "untrue" face-name learning task. ET showed
      overt recognition of some famous faces using a procedure based on Sergent and
      Poncet's (1990) semantic activation task. The pattern of impairment of ET's face
      processing abilities is interpreted in terms of an interactive activation model
      of face processing.

PMID- 7805382
TI  - Associative visual agnosia and alexia without prosopagnosia.
AB  - Disagreement over the neuroanatomical substrate of associative visual agnosia
      encompasses such basic issues as: (1) the necessity for bilateral lesions; (2)
      the intrahemispheric locus of damage; and (3) the roles of disconnection versus
      cortical damage. We examined three patients whose associative visual agnosia
      encompassed objects and printed words but spared faces. CAT scans revealed
      unilateral dominant occipitotemporal strokes. CAT scans of four previously
      reported cases with this same profile of associative agnosia were obtained.
      Dominant parahippocampal, fusiform and lingual gyri were the most extensively
      damaged cortical regions surveyed and were involved in all cases. Of white matter
      tracts surveyed, only temporal white matter including inferior longitudinal
      fasciculus was severely and universally involved. Splenium of the corpus callosum
      was frequently but not always involved. We conclude there is a form of
      associative visual agnosia with agnosia for objects and printed words but sparing
      face recognition which has a characteristic unilateral neuropathology. Damage or
      disconnection of dominant parahippocampal, fusiform and lingual gyri is the
      necessary and sufficient lesion.

PMID- 7805383
TI  - Lateral preferences and visual field asymmetries: appearances may have been
      overstated.
AB  - A review of a sample of the literature on differences in visual half field (VHF)
      asymmetries between left- and right-handed subjects, showed that hand preference
      only had a small influence on VHF superiorities. Across studies, the effect
      usually was in the expected direction, but within studies, it rarely reached
      significance. The finding was replicated in two new empirical studies, one with a
      task that yielded a right VHF superiority (word naming), and one with a task that
      returned a left VHF superiority (symmetry detection). A comparison with other
      lateral preferences (footedness, earedness, and eyedness) indicated that the VHF
      asymmetry of the word naming task was better predicted by ear preference than by
      hand preference; no such superiority was found for the symmetry detection task,
      where no lateral preference correlated significantly with the VHF asymmetry.

PMID- 7805384
TI  - How convincing is the evidence for cognitive slowing in Parkinson's disease?
AB  - The issue of whether or not Parkinson's disease (PD) patients process information
      more slowly than normal is unresolved. Across a range of paradigms the evidence
      for slowing is scant, and many show no slowing. Even the results of a single
      experimental paradigm can be conflicting; some studies have obtained evidence for
      slowed memory scanning in subgroups of PD patients whereas others have not. The
      present study sought the cause of these discrepant results. Old-old (n = 11) and
      young-old (n = 7) PD subjects and controls (n = 16, n = 9) completed both fixed
      and varied set versions of the memory scanning task. No evidence for slowing in
      PD was found. These results indicated that PD did not interact with age or task
      version in its effects on information processing rates in the memory scanning
      task. It was concluded that PD patients do not have any cognitive slowing that is
      detectable with the memory scanning task.

PMID- 7805385
TI  - Visual agnosia and optic aphasia: are they anatomically distinct?
AB  - A patient with left infero-medial occipital-temporal infarct suffered a visual
      agnosia that, by a minor change of the task, could be manipulated to optic
      aphasia. Tools in actual use and pantomimes of tool use were better named than
      stationary tools, a dissociation that suggests differences in the ability of
      stimuli to evoke associations over multiple modalities. Based on this case and
      analysis of previous reports we suggest that optic aphasia differs from visual
      agnosia primarily in the degree of callosal disconnection and that the preserved
      demonstration of tools use and semantic classification of optic aphasia reflect
      right hemisphere contribution to visual processing.

PMID- 7805386
TI  - Post-traumatic retrograde amnesia with selective impairment of autobiographical
      memory.
AB  - A selective, temporally limited retrograde amnesia, confined to autobiographical
      memory, was the only sequela of a "minor" head trauma in two young men. The
      retrograde memory gap covered about one year of life before the trauma and
      persisted for several months, without any anterograde deficit or other cognitive
      disturbances. This unusual pattern of retrograde amnesia deserves close
      consideration and points to the dissociation of memory subsystems and mechanisms.

PMID- 7805387
TI  - Interictal language fluency in temporal lobe epilepsy.
AB  - Mild language production difficulties, particularly in confrontation naming, have
      been documented previously in patients with left temporal lobe epilepsy (LTLE).
      These difficulties, however, do not seem to be reflected in the conversational
      speech of these patients. In order to compare speech fluency in patients with
      left and right temporal lobe epilepsy (RTLE) experimentally, we studied global
      pause-to-speech ratios in patients with unilateral temporal lobe epilepsy, using
      cases with primary generalized epilepsy (PGE) as controls. We hypothesized that
      left-sides cases would exhibit longer pause durations than right-sided cases.
      Speech samples were elicited by asking subjects to describe five different New
      Yorker cartoons, with three repetitions of each description. Phonation was
      converted to graphic output, and pauses between 200 ms and 4000 ms were summated
      and divided by total phonation time. This measure did not discriminate
      significantly between the groups, although the LTLE group tended to pause longer
      than the RTLE or PGE groups. Increased variability in pause duration in the LTLE
      group during cycle 1 suggested that some individuals with LTLE are vulnerable to
      disruption when planning demands are high. A post hoc correlational analysis
      showed that variation in fluency was primarily explained by orthographically
      based lexical retrieval, suggesting that individual differences in fluency are
      related to limitations in a high-level capacity relevant to the production of
      speech. It is unlikely that such limitations are specific to LTLE.

PMID- 7805388
TI  - Phantom limb experiences in congenital limb-deficient adults.
AB  - This case report describes phantom limbs in four adults with congenital limb
      deficiency. Case 1, with congenital absence of the left arm below the elbow,
      received a minor injury of the stump at age 16 and subsequently developed a full
      length phantom arm, hand and fingers. Cases 2 and 3, at the ages of 26 and 30,
      underwent minor surgery of the lower limbs and subsequently developed vivid, full
      length phantoms of their legs. Case 4, aged 31, was born with a shortened and
      deformed right leg, and underwent amputation of the foot and deformed part of the
      leg at age 3. Beginning at age 6, she developed a full-length phantom leg and
      foot that touched the floor, which persisted for more than 20 years. The
      descriptions by these four adults lend credibility to earlier reports of phantom
      limbs in congenital limb-deficient children. They also indicate that these
      phantoms may persist into adulthood.

PMID- 7805389
TI  - Hierarchical stimuli and hemispheric specialization: two case studies.
AB  - Local versus global visual processing was examined in two patients with massive
      unilateral left hemisphere lesions using a directed attention task involving
      hierarchical stimuli. Previous studies found an impressive global advantage in
      patients with posterior left hemisphere lesions on similar tasks. In addition,
      whereas patients with left inferior parietal lobule (IPL) lesions showed the
      global interference on local processing that is typically observed in normals,
      patients with lesions centered on the superior temporal gyrus (STG) demonstrated
      no interference. Paradoxically, our two patients who had complete destruction of
      both the left IPL and STG regions showed an overall local advantage due to local
      interference on global processing. We propose that following extensive left
      hemisphere damage, the isolated right hemisphere may be able to perform
      efficiently the type of processing usually ascribed to the left hemisphere (i.e.,
      local). However, at least under certain conditions, this apparent functional
      plasticity seems to occur at the expense of the type of processing normally
      associated with the right hemisphere (i.e., global).

PMID- 7805390
TI  - Pure dysgraphia with relative sparing of lower-case writing.
AB  - We describe the cognitive analysis of a patient with acquired pure dysgraphia.
      She presented a peculiar dissociation between lower- and upper-case handwriting:
      lower-case writing was relatively spared and showed a significant superiority of
      words versus nonwords. Upper-case writing and oral spelling did not show lexical
      effects, but were affected by item length. In all modalities errors consisted
      mainly of single graphemic substitutions, deletions, insertions and
      transpositions, resulting in legal or illegal nonwords, and showed a similar
      distribution across letter positions. These findings were suggestive of an
      impairment of the graphemic output buffer, which however revealed itself to
      different degrees in the two handwriting styles.

PMID- 7805391
TI  - Independent properties of normal hemispheric specialization predict some
      characteristics of visuo-spatial neglect.
AB  - We derive some predictions about the character of left visuo-spatial neglect from
      two independent characteristics of normal hemispheric specialization: the
      contralateral orientation bias of each hemisphere and the association of local
      and panoramic processing with the left and right hemispheres, respectively. The
      predictions are then tested in three sets of experiments that manipulate focal
      and panoramic attention in estimations of the midpoints of lines and outline
      squares. The results from one patient are consistent with the model and with
      previously reported data from the same patient (Halligan and Marshall, 1993a) on
      a different task (line cancellation).

PMID- 7805392
TI  - Concurrent finger-tapping in mathematically gifted males: evidence for enhanced
      right hemisphere involvement during linguistic processing.
AB  - O'Boyle and Benbow (1990) have suggested that enhanced involvement of the right
      hemisphere (RH) during basic information processing is a neuropsychologic
      characteristic of the gifted brain. To provide converging evidence for this
      hypothesis, the present study was conducted using a concurrent finger-tapping
      paradigm. Specifically, 24 mathematically precocious and 16 average ability
      adolescent males were required to tap a key as quickly as possible while sitting
      silently (baseline condition), concurrently reading a paragraph aloud (verbal
      load), or encoding a random form into memory (spatial load). For average ability
      subjects, the concurrent verbal load reduced tapping rate for the right but not
      the left hand, reflecting a division of LH resources between linguistic
      processing of the paragraph and motor control of the contralateral hand. In
      contrast, for gifted subjects, both their left- and right-hand tapping rates were
      significantly reduced, suggesting that both hemispheres were engaged during
      verbal processing. The concurrent spatial task produced a small but reliable
      reduction in finger-tapping rate for both the left and right hand in each group.
      These findings provide additional support for the notion that enhanced reliance
      on RH functioning is a physiological correlate of mathematical precocity in
      gifted males.

PMID- 7805393
TI  - Distribution of phosphate-activated glutaminase-like immunoreactivity in the
      retina of rodents.
AB  - The distribution of phosphate-activated glutaminase-like immunoreactivity was
      examined in the retinas of rodents. Intense glutaminase immunoreactivity was
      observed in many neuronal perikarya in the ganglion cell layer and inner nuclear
      layer including those of ganglion, bipolar and amacrine cells and possibly
      horizontal cells. Almost all bipolar cells containing protein kinase C were
      immunoreactive for glutaminase, suggesting that the majority of glutaminase
      immunoreactive bipolar cells were of the ON type. Intense glutaminase
      immunoreactivity was also found in the neuropil of the inner and outer plexiform
      layers and around the outer limiting membrane. Weak to moderate immunoreactivity
      was seen in the outer nuclear layer and photoreceptor inner and outer segments.
      Under electron microscopy, glutaminase immunoreactivity was seen in bipolar cell
      axons and amacrine cell processes in the inner plexiform layer. In the outer
      plexiform layer, immunoreactivity was found in the Muller cell processes, but not
      in the photoreceptor cell terminals. These results indicate that ganglion cells
      and ON type bipolar cells use glutaminase to produce transmitter glutamate and
      suggest glutaminase has additional roles in Muller cells. A population of
      amacrine cells and horizontal cells showed immunoreactivity to glutaminase.

PMID- 7805394
TI  - Characterization of an endogenous metalloproteinase in human vitreous.
AB  - The vitreous is a gel-like connective tissue that undergoes liquefaction during
      aging and pathological processes. We isolated and characterized a degradative
      enzyme from the vitreous of different species and identified it to be matrix
      metalloproteinase-2 (MMP-2). This enzyme was found in a latent form and may be
      associated with endogenous inhibitors. Vitreous isolated from both non-diabetic
      and diabetic patients contained MMP-2 in the same concentrations. However, the
      diabetic samples had an additional gelatinase activity at 92 kDa which may be
      associated with a compromised vasculature. These results suggest that the normal
      human vitreous contains an endogenous MMP and the appearance of an additional
      activity is associated with pathologic conditions.

PMID- 7805395
TI  - Phaco-emulsification causes the formation of cavitation bubbles.
AB  - There have been reports of complications arising from damage to non-lenticular
      ocular tissue during the increasingly popular procedure of cataract extraction
      with phaco-emulsification. One cause of this damage might be the formation of
      cavitation bubbles. Such bubbles are known to produce free radicals and shock
      waves. This paper demonstrates directly the formation of cavitation bubbles at
      the tip of the phaco-probe. It also shows the importance of a smooth probe
      profile in reducing bubble formation. Recommendations are made for probe and tip
      design and for the use of minimum power during the surgical procedure of phaco
      emulsification.

PMID- 7805396
TI  - Long term effects of diaminophenoxypentane in the rat retina: protection against
      light damage.
AB  - The retinotoxic drug diaminophenoxypentane (DAPP) was administered to rats to
      determine its long term effects on rhodopsin levels, retinal morphology and the
      retina's susceptibility to damage from visible light. In rats given 2
      intraperitoneal injections of DAPP at doses of 65 mg/kg body wt, there was a
      dramatic and sustained loss of rhodopsin. One wk later visual pigment levels were
      41% lower than in comparable dark maintained rats injected with saline. Rhodopsin
      levels in the DAPP treated rats remained lower than in control animals for the 13
      wk period of the study. Morphologically, the ROS of rats 1-2 wks after DAPP
      treatment exhibited some disorganization and shortening; the RPE was
      unremarkable. Seven wks after DAPP treatment an occasional focal area of damage
      was seen in the RPE. Similarly, focal areas of degeneration were seen in the
      outer nuclear layer between the rows of photoreceptor cells. As determined by
      photoreceptor cell nuclear counts, the retinotoxic effect of DAPP persisted long
      after drug administration. In the treated rats the loss of visual cell nuclei was
      11% at 7 wks; it was 22% 13 wks after DAPP treatment. Immediately after exposure
      to intense visible light, damage was seen in both the photoreceptor cells and RPE
      of DAPP treated rats. However, the effects of exposure in the treated rats were
      less dramatic than in retinas from rats without DAPP treatment. Following a 2 wk
      dark recovery period, the DAPP treated rats had a normal appearing retinal
      morphology and an intact RPE layer. The retinas of rats without DAPP treatment
      showed extensive visual cell and RPE loss.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7805397
TI  - Growth regulation of retinal pigment epithelial (RPE) cells in vitro.
AB  - Studies of growth factor production by chick embryo retinal pigment epithelial
      (RPE) cells and the effects of cytokines on chick and human RPE cells were
      performed in vitro. RPE cell growth was evaluated by tritiated thymidine uptake.
      Chick RPE cells produced growth factors whose molecular weights were 15 and 108
      kD. These fractions contained interleukin (IL)-1-like activity which stimulated
      murine thymocyte proliferation. 100-150 U/ml human IL-1 beta, interferon (IFN)
      beta, IFN-gamma and tumor necrosis factor (TNF)-alpha stimulated the growth of
      both RPE cells. The activity of IFN-beta was the most potent of these cytokines,
      while IL-2 and IFN-alpha had no effect in chick RPE cells. 100-150 U/ml
      transforming growth factor (TGF)-beta 1 suppressed cytokine-induced growth of
      both RPE cells. RPE cells therefore produce growth factors, respond to several
      growth factors and are regulated by a network of cytokines.

PMID- 7805398
TI  - Distribution of heparan sulfate proteoglycans in embryonic chicken neural retina
      and isolated inner limiting membrane.
AB  - Quantitative distribution of proteoglycans was studied in retinal neural
      epithelium and its basement membrane (inner limiting membrane). Heparan sulfate
      proteoglycans (HSPGs) were primarily associated with both inner and outer
      plexiform (synaptic) layers, and inner limiting membrane (ILM), as determined by
      autoradiographs of lyase-digested cryosections. Based on distribution of 35S
      sulfate-labeled proteoglycans, the isolated ILM contained on average
      approximately three fourths of its proteoglycans as HSPGs and one fourth as
      chondroitin sulfate/dermatan sulfate proteoglycans (CS/DSPGs), whereas the
      remaining retina contained approximately equal amounts of the two proteoglycans
      (PGs). Immunohistochemical staining indicates that the core proteins of the HSPGs
      in the ILM are distinct from those of the plexiform layers. The photoreceptor
      layer, which other studies have shown to contain much of the extracellular
      CS/DSPGs, was not examined. Enrichment of distinct HSPGs in the ILM and plexiform
      layers support the conclusion that the HSPGs may be intimately involved in the
      different developmental events characterizing the two regions: development and
      extension of ganglion cell axons in the former, synaptogenesis and neuronal
      function in the latter.

PMID- 7805399
TI  - Outwardly rectifying potassium currents in lens epithelial cell membranes.
AB  - Isolated epithelial cells from chick, pig, monkey, rabbit, bovine, and human
      lenses contain K+ channels that often turn on with a delay after a voltage step
      and have a larger macroscopic conductance for outward currents than for inward
      currents even with the same K+ concentration on both sides of the membrane. These
      outward rectifiers are quite diverse between different lens types and more than
      one kind can be present even within a single lens species. The channels differ
      substantially in the voltage dependence of their opening, their deactivation time
      constants, and the time course of their inactivation. Most produce currents of
      the delayed rectifier type but others show similarities to A-type currents.
      Because these different channels open at different voltages, inactivate to
      different degrees and represent different fractions of the total conductance from
      one lens cell to another, their contribution to the resting voltage is not the
      same in all cells investigated. These currents are the most frequently occurring
      in bovine, pig, monkey, and human lens epithelium and also occur commonly in
      chick lens epithelium. They occur less frequently in rodents.

PMID- 7805400
TI  - Photosensitivity of the isolated pigment epithelium and arachidonic acid
      metabolism: preliminary results.
AB  - The administration of 0.1-0.5% of ethanol produces a slow increase in the
      transepithelial potential (TEP) of about 2 mV in the bovine pigment epithelium
      (RPE) under ordinary room lighting. However, virtually no response could be
      observed when ethanol was administered in the dark. Because of this apparent
      light sensitivity, the ethanol induced response (EIR) was investigated to
      determine its spectral response characteristics, temporal interaction with light,
      and the effects of a variety of metabolic inhibitors as well as pertussis and
      cholera toxins. The spectral response curve peaked at 520 nm with a narrow half
      width. The EIR was found to be inhibited by pertussis toxin but not cholera
      toxin. Inhibition of either phospholipase A2 or lipoxygenase/cyclooxygenase
      resulted in a marked inhibition of the EIR. The incubating solutions of the
      apical surface of bovine and cultured chick embryo RPE were analyzed by RP-HPLC
      under conditions of weak white light and darkness. Two peaks in the chromatogram
      were observed to vary with these conditions and the presence of
      nordihydroguaiaretic acid simulated the effects of darkness. The RP-HPLC studies
      did not involve the employment of ethanol. Two different experimental procedures
      revealed the photosensitivity of the isolated RPE to weak light and suggest that
      light initiates or promotes arachidonic acid metabolism. A possible regulatory
      effect of retinoids was also indicated.

PMID- 7805402
TI  - Treatment looks easy.

PMID- 7805401
TI  - Stereological estimation of Weibel-Palade bodies in the retinal vasculature of
      normal and diabetic dogs.
AB  - The absolute volume of Weibel-Palade (WP) bodies, the storage organelles of von
      Willebrand factor (vWF), was estimated by a stereological method in a known
      volume of central retina from normal and 5-year diabetic dogs. The results showed
      that the volume of WP bodies present in the endothelium of the retinal
      vasculature varies with blood vessel type and in diabetes. In both diabetic and
      normal dogs the endothelium of the retinal veins contained a higher volume of WP
      bodies than that of the retinal arteries. In dogs which had been diabetic for a
      duration of 5 years the volume of WP bodies present in the endothelium of retinal
      veins was significantly greater than in the endothelium of veins from the control
      animals. However, there was no significant difference in the volume of WP bodies
      present in the endothelium of retinal arteries or capillaries between the two
      groups of animals.

PMID- 7805403
TI  - Allergic contact dermatitis and patch testing in childhood.

PMID- 7805404
TI  - A dermatologic diary. Portrait of a practice.

PMID- 7805405
TI  - Juvenile xanthogranuloma.

PMID- 7805407
TI  - Chordoma with cutaneous metastasis.
AB  - Chordoma is a neoplasm arising from the primitive notochord. Even though many
      chordomas follow a progressive course with multiple recurrences and metastases
      and eventual death due to tumor, reports of skin metastases from chordoma are
      rare. This report describes a case of chordoma with metastasis to the scalp in a
      67-year-old man with a primary lesion of the sacrococcygeal region.

PMID- 7805406
TI  - Beau's lines and pyogenic granulomas following hand trauma.
AB  - We report two cases of trauma-induced Beau's lines accompanied by pyogenic
      granulomas of the proximal nail folds of the affected fingers. The preceding
      trauma was not directly to the nail matrix but was more proximal, on the palm in
      one case and the arm in the other. The simultaneous occurrence of Beau's lines
      and pyogenic granulomas following trauma has not been reported previously in the
      literature.

PMID- 7805408
TI  - Occult tooth fragments spontaneously extruded after six months.
AB  - Fracture of one or more teeth is a frequent complication of trauma to the oral
      cavity. Broken teeth that are not accounted for are often presumed to be
      swallowed or lost. We report a case of fracture of incisors that were not located
      on physical examination following the trauma but were discovered six months later
      as hard, perforating papulonodules on the lower lip.

PMID- 7805409
TI  - Unilateral pseudo-Kaposi's sarcoma (Bluefarb-Stewart type).
AB  - Unilateral pseudo-Kaposi's sarcoma has been associated with Klippel-Trenaunay
      syndrome. A case is described here of a 17-year-old man in whom clinical and
      histopathologic findings suggested pseudo-Kaposi's sarcoma of this type. In
      addition to Kaposi's sarcoma, this entity should be differentiated from
      lymphangioendothelioma and lymphangioma. Positive factor VIII reactivity, which
      is evident in our case, may eliminate confusion.

PMID- 7805410
TI  - Two unusual cases of anhidrosis.
AB  - Many disorders produce anhidrosis, including abnormalities of the central or
      peripheral nervous system. Tumors, infarcts, injuries, or hemorrhages of the
      brain can be the cause. We describe two patients with anhidrosis due to
      neurologic causes. One patient had an acquired complete left unilateral
      anhidrosis without an ipsilateral Horner's syndrome. The other patient showed the
      second case associated with congenital Horner's syndrome reported in the
      dermatologic literature. The patient with unilateral anhidrosis had multiple
      infarcts noted on computed axial tomography and magnetic resonance imaging of his
      head and spine, which were thought to be the cause of his anhidrosis. Congenital
      Horner's syndrome is rare, but can be differentiated from other causes of
      Horner's syndrome by the finding of hypochromia of the affected iris, as in our
      patient. We present two patients with anhidrosis due to conditions with which the
      practitioner may not be familiar.

PMID- 7805411
TI  - Breast deformity produced by morphea in a young girl.
AB  - We report a patient who presented with morphea of the chest wall, and later
      showed an unusual marked deformity of the breast. We also discuss the
      differential diagnosis of acquired breast hypoplasia as a complication of a skin
      disorder.

PMID- 7805412
TI  - Treatment of an amalgam tattoo with the Q-switched ruby laser.
AB  - The amalgam tattoo is an asymptomatic, ill-defined pigmented macule or patch on
      the gingiva, buccal mucosa, or mucobuccal fold. It can be cosmetically
      disfiguring if present on the anterior gingiva. The only reported treatments have
      involved extensive surgery and grafting. We report use of the Q-switched ruby
      laser to remove a gingival amalgam tattoo.

PMID- 7805413
TI  - Better dermatologic office photography: taking the photograph.
AB  - In a previous article we reviewed the questions every medical photographer must
      ask when looking through the viewfinder, as well as the difference between
      plastic surgical and dermatologic photography. We conclude by offering a mnemonic
      for the three views necessary in dermatologic photography: Location, Scan, and
      Detail, and by suggesting a technique for preadjusting the camera, lens setting,
      and flash that will guarantee consistent, high-quality clinical photos.

PMID- 7805414
TI  - Primary cutaneous mucormycosis with a Mucor species: is iron overload a factor?
AB  - A severely debilitated patient showed primary cutaneous mucormycosis with a Mucor
      species at a tape erosion site. The pathogenic nature and epidemiologic features
      of this unusual fungal infection are reviewed to emphasize its recognition in the
      differential diagnosis of ischemic lesions in immunocompromised patients. Iron
      overload may be a risk factor for mucormycosis.

PMID- 7805415
TI  - Tularemia.
AB  - Clinical and histologic characteristics of tularemia are reviewed in this report
      of a 65-year-old man who presented with fever, cutaneous ulceration, and regional
      lymphadenopathy. Examination of a biopsy specimen failed to demonstrate the
      granulomatous inflammation one would expect according to the current dermatologic
      literature. We review the diagnostic implications of this finding.

PMID- 7805416
TI  - An Id reaction to Mycobacterium leprae: first documented case.
AB  - We present a case of generalized sarcoidal dermatitis in a patient with
      tuberculoid leprosy. After careful consideration of the reactional states in
      leprosy and recognizing that id reactions occur in other mycobacterial
      infections, we concluded that the patient's eruption was likely an id reaction to
      his Mycobacterium leprae infection. It was most reminiscent of the tuberculids:
      lichenoid tuberculid and lichen scrofulosorum. However, its histomorphologic
      appearance was distinctive, showing elongated granulomata along with foci of
      incipient perineural granuloma formation, similar to the histomorphologic
      appearance of tuberculoid leprosy. A pathogenetic mechanism for this unique
      eruption is reviewed briefly.

PMID- 7805417
TI  - Muscarinic receptor regulation of the esophagus and lower esophageal sphincter.

PMID- 7805418
TI  - Epidemiology and dysphagia.
AB  - With few exceptions, epidemiology of dysphagia is unexplored, particularly with
      regard to risk and protective factors, and underutilized. The range of incidence
      of dysphagia in selected primary diagnoses often associated with dysphagia is
      summarized.

PMID- 7805419
TI  - Neurophysiology of swallowing in the aged.
AB  - The neurophysiology of normal swallowing and its alterations related to age are
      reviewed. Clinical implications in health and disease are discussed.

PMID- 7805420
TI  - Effect of aging on the deglutitive oral, pharyngeal, and esophageal motor
      function.
AB  - Aging affects some members of the swallowing orchestra and spares the others. It
      seems that changes in the pharynx of the elderly are more of a positive nature
      than a negative one and reflect an adaptation to age-induced structural changes
      of the upper esophageal sphincter. In the esophagus, the positive change in
      deglutitive peristaltic amplitude and duration seem to revert to a negative one
      over the age of 90 years. In the upper esophageal sphincter, it appears that
      aging reduces the resting pressure, but spares its response to various stimuli.
      Considering the increasing elderly population and their medical needs, further
      normalcy data about various manometric aspects of deglutition is needed for
      physiologic studies as well as diagnostic and therapeutic purposes.

PMID- 7805421
TI  - An update on the physiology of the components of the upper esophageal sphincter.
AB  - The upper esophageal sphincter is composed of both opening and closing muscles.
      The opening muscles include the thyrohyoideus and the geniohyoideus, and the
      closing muscles include the cricopharyngeus, thyropharyngeus, and cervical
      esophagus. The relative contribution of each muscle to the opening and closing of
      the UES varies with the physiologic state. Although the cricopharyngeus may be
      the primary muscle of the UES, it cannot account for all of the observed
      functions of the UES.

PMID- 7805422
TI  - Determination of the risks and benefits of oral feeding.
AB  - The dysphagia team is often faced with the dilemma of whether or not to let
      patients with known aspiration feed orally. The criteria that assist
      professionals in their final decisions may be more anecdotal than empirical.
      Undoubtedly, the decision-making process that is activated in determinations of
      oral vs. non-oral feeding will vary among institutions and by patient
      presentation. For some dysphagia teams, the presence of tracheal penetration of
      swallowed contents is sufficient indication to preclude oral feeding. For others,
      some amounts of aspiration are acceptable.

PMID- 7805423
TI  - Dysphagia following head and neck cancer surgery.
AB  - Surgical resection of head and neck cancer results in predictable patterns of
      dysphagia and aspiration due to disruption of the anatomic structures of
      swallowing. Common procedures undertaken in the treatment of head and neck cancer
      include tracheostomy, glossectomy, mandibulectomy, surgery on the palate, total
      and partial laryngectomy, reconstruction of the pharynx and cervical esophagus,
      and surgery of the skull base. An overview is presented of normal swallowing
      physiology, as well as swallowing perturbations that are frequently encountered
      in postoperative head and neck cancer patients.

PMID- 7805425
TI  - Indications and techniques of endoscopy in evaluation of cervical dysphagia:
      comparison with radiographic techniques.
AB  - The technique of fiberoptic endoscopic evaluation of swallowing disorders (FEES),
      and a comparison of its utility with that of videofluoroscopic examination in
      patients with dysphagia, was presented in a workshop session. Viewpoints were
      expressed by two speech pathologists and an otolaryngologist experienced in
      assessment and treatment of patients with dysphagia, and representative cases,
      illustrated with videotaped FEES and videofluoroscopic studies, were discussed.
      Some of the major advantages and disadvantages of each of these modalities are
      discussed in the following three articles.

PMID- 7805426
TI  - Controlled prospective study of oral ciprofloxacin versus amoxycillin/clavulanic
      acid in chronic suppurative otitis media in adults.
AB  - The efficacy and tolerability of ciprofloxacin (500 mg twice daily) was compared
      with that of amoxycillin/clavulanic acid (500 mg three times daily) in 76
      patients with acute exacerbations of chronic non-cholesteatomatous suppurative
      otitis media enrolled in this open randomized multicentre trial. A total of 40
      ciprofloxacin-treated patients and 35 amoxycillin/clavulanic acid-treated
      patients were evaluable for clinical efficacy following the 9-day treatment
      period. Pseudomonas aeruginosa was the main pathogen isolated prior to treatment.
      At the end of treatment, otorrhoea had disappeared in 57.5% of the ciprofloxacin
      group and 37.1% of the amoxycillin/clavulanic acid group (p = 0.04). Bacterial
      eradication rate was also significantly greater with ciprofloxacin (69.7%) than
      with amoxycillin/clavulanic acid (27.3%). Both treatments were well tolerated.
      Ciprofloxacin appears to be an effective treatment of chronic otitis media, and
      superior to amoxycillin/clavulanic acid.

PMID- 7805424
TI  - Neurogenic dysphagia: what is the cause when the cause is not obvious?
AB  - The potential causes of neurogenic oropharyngeal dysphagia in cases in which the
      underlying neurologic disorder is not readily apparent are discussed. The most
      common basis for unexplained neurogenic dysphagia may be cerebrovascular disease
      in the form of either confluent periventricular infarcts or small, discrete
      brainstem stroke, which may be invisible by magnetic resonance imaging. The
      diagnosis of occult stroke causing pharyngeal dysphagia should not be overlooked,
      because this diagnosis carries important treatment implications. Motor neuron
      disease producing bulbar palsy, pseudobulbar palsy, or a combination of the two
      can present as gradually progressive dysphagia and dysarthria with little if any
      limb involvement. Myopathies, especially polymyositis, and myasthenia gravis are
      potentially treatable disorders that must be considered. A variety of medications
      may cause or exacerbate neurogenic dysphagia. Psychiatric disorders can
      masquerade as swallowing apraxia. The basis for unexplained neurogenic dysphagia
      can best be elucidated by methodical evaluation including careful history,
      neurologic examination, videofluoroscopy of swallowing, blood studies (CBC,
      chemistry panel, creatine kinase, B12, thyroid screening, and anti-acetylcholine
      receptor antibodies), electromyography, and magnetic resonance imaging (MRI) of
      the brain, plus additional procedures such as lumbar puncture and muscle biopsy
      as indicated. Little is known about aging and neurogenic dysphagia, specifically
      the relative contributions of natural age-related changes in the oropharynx and
      of diseases of the elderly, including periventricular MRI abnormalities, in
      producing dysphagia symptoms and videofluoroscopic abnormalities in this
      population.

PMID- 7805427
TI  - Study of the efficacy and safety of ciprofloxacin in the treatment of chronic
      sinusitis.
AB  - Over a 12-month period, 56 patients with acute exacerbations of chronic sinusitis
      were included in this study. The mean age of the patients was 48.6 +/- 10.1
      years. The period between the onset of sinus symptoms and inclusion in the study
      was 10.1 +/- 12.1 years and the exacerbation had lasted 2.4 +/- 4.4 months.
      Patients were given 500 mg ciprofloxacin twice daily for 9 days. Bacteriological
      specimens taken at inclusion were positive in 53.6% of cases, 25 Gram-positive
      and 16 Gram-negative pathogens being isolated. At the end of the treatment,
      rhinorrhoea, which was the main criterion for evaluation of the efficacy of
      treatment, had disappeared in 46/54 (85%) patients who were examined. Of the 30
      patients whose sinusitis was confirmed by bacteriological test, the bacteria were
      eradicated in 90% of cases. At the end of a 4-week follow-up period after the end
      of treatment, the clinical success rate was 74.5%, the partial success rate 21.2%
      and the failure rate 4.3%. There were no bacteriological recurrences. Ten adverse
      events were observed in seven patients and in four (7%) of these treatment had to
      be withdrawn. This study showed ciprofloxacin to be an effective and well
      tolerated treatment for exacerbations of chronic sinusitis treated in non
      hospital practice.

PMID- 7805428
TI  - Study of the efficacy and safety of ciprofloxacin in the treatment of chronic
      otitis.
AB  - Over a period of 18 months 76 patients presenting with acute exacerbations of
      chronic otitis were enrolled in this study. The mean age of the patients was 46.4
      +/- 16.8 years, the interval between the onset of symptoms of otitis and
      enrollment in the study was 22.1 +/- 19.4 years and the infective episode had
      been developing for 36.4 +/- 72.4 days. The patients received either 500 or 750
      mg ciprofloxacin twice daily for a period of 9 days with no topical antibiotic
      treatment. The bacteriological specimen taken at enrollment was positive in 93%
      of the patients and led to the isolation of 85 microorganisms, 65% of which were
      Pseudomonas aeruginosa, Staphylococcus aureus or Proteus mirabilis. At the end of
      the treatment period, discharge from the ears (the primary clinical evaluation
      criterion) had ceased in 44/69 (64%) patients examined. The clinical cure rate
      was 23/39 (59%) for patients treated with 500 mg ciprofloxacin twice daily and
      21/30 (70%) for those treated with 750 mg twice daily (difference was not
      statistically significant). At the end of a 4-week post-treatment follow-up, the
      clinical relapse rate was 7%. There was no relapse in the patients with chronic
      otitis which had been bacteriologically documented. Eight adverse effects were
      observed in five patients and treatment had to be discontinued in one case. This
      study shows ciprofloxacin to be an effective and safe agent for use in the
      treatment of acute exacerbations of chronic otitis treated in general practice.
      In certain cases, however, additional treatment with a topical antibiotic may be
      desirable.

PMID- 7805429
TI  - Study of the distribution of oral ciprofloxacin into the mucosa of the middle ear
      and the cortical bone of the mastoid process.
AB  - This multicentre study evaluates the distribution of ciprofloxacin into the
      tissue structures of the middle ear following multiple dosing of one 500 mg
      tablet every 12 h. The samples were taken perioperatively from adult patients due
      to undergo surgery for chronic otitis. Administration of ciprofloxacin was
      instigated 9 days prior to the operation. The samples were taken at different
      intervals after the last dose in order to evaluate variations in concentration
      with time. The average peak concentrations recorded and the time taken to reach
      these concentrations were as follows: middle ear mucosa (n = 16): 5.54 +/- 3.46
      micrograms/g (3-4 h): cortical bone of the mastoid process (n = 21): 1.07 +/-
      1.29 micrograms/g (4 h). The measurements carried out 12 h after the last dose
      show that concentrations of ciprofloxacin in the middle ear mucosa were still at
      least as high as the minimum inhibitory concentration for this antibiotic for
      most of the pathogens implicated in acute exacerbations of chronic otitis. These
      results suggest that, administered as an oral dose of 500 mg every 12 h,
      ciprofloxacin may be an effective agent for the treatment of chronic suppurative
      otitis. These results now need to be backed up by clinical trials.

PMID- 7805430
TI  - Ciprofloxacin in the treatment of malignant external otitis.
AB  - Malignant external otitis is a serious infection most frequently caused by
      Pseudomonas aeruginosa. Because of its antipseudomonal activity and good tissue
      penetration, ciprofloxacin is an antibiotic which should, in theory, be effective
      in the treatment of this type of infection. Publications on the use of
      ciprofloxacin in the treatment of malignant external otitis are analysed below.
      This paper analyses 84 clinical case studies collected from 13 publications:
      ciprofloxacin, administered for the most part orally, was given in a dosage of
      750 mg twice daily, apart from three studies where a lower dosage of 500 mg twice
      daily was used. When the drug was administered parenterally, the dosage was 200
      mg b.i.d. In one publication, ciprofloxacin was used in combination with
      rifampicin. The average duration of treatment was 3 months. Ps. aeruginosa was
      isolated in 82 patients and sensitivity tests were carried out on 47 strains,
      none of which was resistant to ciprofloxacin. The clinical cure rate was 96.4%
      (84 patients). The rate of bacteriological eradication was close to 100% in the
      76 evaluable patients. Long-term follow-up (between 2 and 44 months) showed that
      clinical and bacteriological cure was maintained in all but two patients.
      Ciprofloxacin thus seems to be a particularly useful antibiotic for the treatment
      of malignant external otitis, both because of its clinical and bacteriological
      efficacy and because it is well tolerated.

PMID- 7805431
TI  - A double-blind comparison of ciprofloxacin and amoxycillin/clavulanic acid in the
      treatment of chronic sinusitis.
AB  - A total of 251 adults with chronic sinusitis were enrolled into this prospective
      multicentre, double-blind, double-placebo comparison of ciprofloxacin (500 mg
      twice daily) with amoxycillin/clavulanic acid (500 mg three times daily). The
      diagnosis of chronic sinusitis (persistence of clinical symptoms for at least 3
      months) was confirmed by computerized tomography scan and/or sinusoscopy prior to
      therapy. Patients at inclusion had purulent or muco-purulent rhinorrhoea.
      Staphylococcus aureus (n = 45), Haemophilus influenzae (n = 35), Streptococcus
      pneumoniae (n = 32) and enterobacteriaceae (n = 31) were isolated from pre
      treatment aspirates of the middle meatus. Treatment lasted 9 days, at the end of
      which nasal discharge disappeared in 71/118 (60.2%) patients of the ciprofloxacin
      group and 69/123 (56.1%) of those in the amoxycillin/clavulanic acid group. The
      clinical cure and bacteriological eradication rates were 58.6% versus 51.2% and
      88.9% versus 90.5% for ciprofloxacin and amoxycillin/clavulanic acid,
      respectively. These differences were not significant, however, amongst patients
      who had a positive initial culture and who were evaluated 40 days after
      treatment. Ciprofloxacin recipients had a significantly higher cure rate than
      those treated with amoxycillin/clavulanic acid (83.3% vs. 67.6%, p = 0.043).
      Clinical tolerance was significantly better with ciprofloxacin (p = 0.012),
      essentially due to a large number of gastro-intestinal related side-effects in
      the amoxycillin/clavulanic acid group (n = 35). Ciprofloxacin proved to be at
      least as effective as amoxycillin/clavulanic acid. The superior safety profile, a
      twice daily dosage regimen, suggests that ciprofloxacin may be a useful
      therapeutic alternative for the treatment of chronic sinusitis.

PMID- 7805432
TI  - ADHD-related behavior among non-referred children: parents' ratings of DSM-III-R
      symptoms.
AB  - To identify the prevalence of ADHD symptoms among non-referred children, parents'
      ratings based on DSM-III-R criteria for ADHD were obtained for 1022 metropolitan
      children of ages 4 to 12. The prevalence rates of fourteen behavior items were
      markedly lower for boys of ages 10-12 than of ages 7-9, and for girls of ages 7-9
      than of ages 4-6. 41.5% of the 7.7% subjects meeting ADHD criteria had been
      identified by their teachers as having problems symptomatic of ADHD, and one
      third had been reported by their parents as having conduct problems and emotional
      difficulties. A factor analysis revealed three factors: inattention;
      hyperactivity; and excessive verbal activities.

PMID- 7805433
TI  - A commentary on adolescent group violence.
AB  - In an effort to understand some of the group dynamic factors inherent in today's
      unprecedented increase in youth gang violence, the larger, well organized gangs
      of the 1960's, were compared with the contemporary crowd-like, small packs of
      street youths. A hypothesis is advanced that the combined processes of de
      individuation and of group contagion underlie many of the violent acts, so
      rampant in inner-city areas.

PMID- 7805434
TI  - Season of birth in infantile autism and other types of childhood psychoses.
AB  - Season of birth in 328 children with infantile autism and other types of
      childhood psychoses born between 1945 and 1980 was compared with that of a
      control population born in the same period. For some parts of the period (the
      years 1951-56, 1963-68 and 1975-80 combined) an excess of March born boys with
      infantile autism was found. For boys with autistic-like disorders, born in the
      same period a maximum occurred in November, while no seasonality was observed for
      a borderline sample.

PMID- 7805435
TI  - Maternal psychiatric disorders in pediatric inflammatory bowel disease and cystic
      fibrosis.
AB  - The mothers of 72 children and adolescents with inflammatory bowel disease (IBD)
      and 44 mothers of children and adolescents with cystic fibrosis (CF) were given A
      SADS interviews. Fifty-one percent of IBD mothers and 41% of cystic fibrosis
      mothers had a lifetime history of depression. More IBD than CF mothers had a
      history of suicide gestures or attempts, and were more likely to have a history
      of obsessive compulsive disorder. However, CF mothers were more likely to have
      experienced panic attacks.

PMID- 7805436
TI  - Child abuse and treatment difficulty in inpatient treatment of children and
      adolescents.
AB  - This study examined the associations between abuse and staff perceived treatment
      difficulty in sixty-nine hospitalized children and adolescents. Subjects were
      rated on a treatment difficulty scale, and clinical charts were reviewed for
      evidence of physical abuse, sexual abuse, abuse between parents, and parental
      history of abuse. Subjects with histories of abuse were not rated as more
      difficult or less responsive to treatment than other patients. Physically abused
      youngsters were rated as more self-destructive and more accessible to treatment
      than non-abused children, while sexually abused youngsters were self-destructive
      and demanding, and their families were seen as more distant and unavailable.

PMID- 7805437
TI  - The concept and diagnosis of multiple systems organ failure.
AB  - There are still controversies concerning the concept and diagnosis of multiple
      systems organ failure (MSOF), since the term does not precisely define its true
      nature, and its differential diagnosis with other irrelevant clinical conditions,
      such as senile dysfunction of organs, agonal state, etc, remains unclarified. Our
      studies on both human burn patients and rat model by means of electron spin
      resonance (ESR) showed that there was an excessive generation of free oxygen
      radicals resulting in lipid peroxidation of cell membrane of various tissues. The
      intestine seemed to be particularly sensitive to hypoperfusion-reperfusion
      injury, as diamine oxidase activity of the ileum was lowered and translocation of
      bacteria occurred, indicating failure of intestinal mucosal barrier function.
      Concomitant determinations of plasma endotoxin (LPS) and tumor necrosis factor
      alpha (TNFa) levels showed significant elevation, especially in patients who
      finally developed MSOF. The data suggested that intestinally derived bacteria
      and/or LPS exacerbate the systemic responses initiated by ischemia reperfusion
      injury and the presence of large amounts of devitalized tissue. Early diagnosis
      is important in order to improve the prognosis. However, current criteria of
      diagnosis for MSOF do not conduce to an early diagnosis, as they only describe
      the end stage manifestations, while our therapeutic strategy should be directed
      against different levels of initiators, systemic mediators, and effectors of
      injury. Therefore, it is important to emphasize the role of septic responses in
      the development of the syndrome. We propose that the name of the syndrome be
      changed to "sepsis with organ dysfunction" or "mediator injury of organs".

PMID- 7805438
TI  - Molecular epidemiologic study of burn wound infection caused by Staphylococcus
      aureus in children.
AB  - 115 children with burn injuries were admitted to the Children's Hospital of
      Chongqing Medical University. Of the 1554 samples, 276 strains of staphylococcus
      aureus were isolated from the burn wounds and other sites. The rate of burn wound
      infection caused by S. aureus was 25.2% (29/115). The 54 epidemic strains of S.
      aureus all carried 1.6 and 1.9 Md plasmid DNAs belonging to phage type 618, and
      were resistant to at least 10 antimicrobial agents, including oxacillin,
      cephalothin and cephaloridine, but sensitive to tobramycin and amikacin.
      Identical plasmid profiles and phage types of isolated S. aureus indicated that a
      patient carrying a multi-resistant strain of S. aureus in his anterior nares
      caused an epidemic of S. aureus wound infection in 13 patients. S. aureus
      isolated from burn wounds of 8 cases were derived from the contaminated hands of
      their family members.

PMID- 7805439
TI  - Clinical use of homograft stored by vitrification.
AB  - Using 20% DMSO and 6% propylene glycol in Kreb' Ringer phosphate solution as
      cryopotective agent for homograft vitrification storage, the viability of stored
      homograft (79.2%) was higher than that of slow cooling storage (59.7%). About
      540000 cm2 of vitrified homograft were used to cover the wounds after excision of
      burn eschar in 135 patients with major burns. The take-rate was over 94%. The
      cryopreservation of skin by vitrification can improve the viability and quality
      of skin and save time and cost.

PMID- 7805440
TI  - A report on selective radiofrequency ablation of dual atrioventricular node
      pathways in 34 cases.
AB  - Selective ablation of slow pathway by radiofrequency (RF) current in 34 patients
      with atrioventricular (AV) node pathways and tachycardia was performed with two
      methods in our section; posterior approach was used in the first 12 patients, the
      slow pathways were ablated successfully. Inferior approach was performed in the
      other 22 patients. Slow pathways were interrupted in 14 patients. Retrograde fast
      pathways and/or slow pathways were ablated in 6 patients. Retrograde fast
      pathways and slow pathways were abolished and antegrade fast pathways were
      injured transitorily in 2 cases. The total procedure time was shorter, RF
      applications were fewer by inferior approach than by posterior approach (P <
      0.05). Both antegrade and retrograde conduction of fast pathways had not been
      affected after slow pathways were ablated (P > 0.05). After a mean of 8 months
      follow-up, two patients recurred and were ablated successfully again. We come to
      the conclusion that inferior approach might be a preferable method compared with
      posterior approach; the slow pathways is the compact node and its posterior input
      of transitional cells; the retrograde fast pathway may be the anterior
      superficial group of transitional cells and is not always in the same location of
      antegrade fast pathway.

PMID- 7805441
TI  - Intracerebral co-grafting of Schwann's cells and fetal adrenal medulla in the
      treatment of Parkinson's disease.
AB  - Intracerebral co-grafting of Schwann's cells and human fetal adrenal medullary
      tissue was performed in 10 patients with Parkinson's disease. One to six months
      after grafting, symptoms were improved significantly for 1 to 3 grade. Among
      them, 2 patients resumed nearly normal daily activities. Long-term follow-up
      showed that the symptoms were not improved satisfactorily in some patients. It is
      considered that careful selection of patients, administration of amantadine, and
      co-grafting of Schwann's cells which prompts the survival of chromaffin cells are
      essential to better results.

PMID- 7805443
TI  - Fertility by rapidly activated sperm from epididymis.

PMID- 7805442
TI  - Amplification of the C-erbB-2(HER-2/neu) proto-oncogene in ovarian carcinomas.
AB  - C-erbB-2(HER-2/neu) proto-oncogene is mainly expressed in epithelial tissue and
      activated due to its amplification. Amplification of the C-erbB-2 proto-oncogene
      has been associated with poor prognosis in human ovarian cancer. Our study was to
      examine whether amplification is more frequently observed in ovarian cancer, or
      it is associated with poor prognosis of human ovarian cancer in China. The DNA of
      ovarian cancers was extracted and consequently digested with restriction
      endonuclease EcoRI, electrophoresed in 0.8% agarose gels and blotted onto
      nitrocellulose filter with Southern transferring method. It was then hybridized
      with a 32P-labelled C-erbB-2 probe and subsequently underwent autoradiography.
      The result has shown that the C-erbB-2(HER-2/neu) gene was amplified in 8 of 26
      human ovarian cancers (30.8%). The clinical data showed that all of the 8 cases
      with the amplified C-erbB-2 were in their advanced stage (III-IV). Five of the
      patients died from 2 to 4 months after operation. These data suggest that
      amplification of the C-erbB-2 gene may play a role in the pathogenesis of ovarian
      carcinoma; it is frequently observed in advanced ovarian cancer and is associated
      with poor prognosis for these patients.

PMID- 7805444
TI  - Immunohistochemical demonstration of CCAAT/enhancer binding protein (C/EBP) in
      human liver tissues of various origin.
AB  - C/EBP is a sequence-specific DNA-binding protein. In order to identify its
      distribution and localization, immunohistochemical technique (ABC method) was
      done using anti-C/EBP polypeptide antibodies 1103#, 425# in liver specimens from
      20 normal adults, 5 neonates, 6 patients with hepatitis, 25 with liver cirrhosis,
      80 with hepatocellular carcinoma (40 cases were associated with surrounding
      nontumorous tissues) and 26 patients with cholangiocarcinoma (15 cases were
      associated with surrounding nontumorous tissues). The results showed that C/EBP
      was diffusely distributed in nuclei and cytoplasm of differentiated liver cells
      and very low or undetectable in liver cancer cells. The manifestation of C/EBP
      correlated with degree of differentiation of tumour cells, and was obviously
      weaker than that in surrounding nontumorous tissues. C/EBP positive staining has
      also been found in regenerating epithelial cells of bile ductules. The results
      suggested that C/EBP should play an important role in establishing and
      maintaining the differentiation of liver cells.

PMID- 7805446
TI  - Transjugular intrahepatic portosystemic stent shunts. Preliminary results in 18
      patients.
AB  - In 18 consecutive patients receiving the transjugular intrahepatic portosystemic
      stent shunts (TIPSS), 15 were male and 3 female. The patients aged from 34 to 66
      years had liver cirrhosis with portal hypertension and esophageal varices. Twelve
      had recurrent bleedings from raptured gastroesophageal varices. Shunts were
      established in 16 of the 18 patients and no operative death was noted. Portal
      vein pressure was reduced from 3.98 +/- 0.24 kPa before shunting to 2.40 +/- 0.16
      kPa after shunting. Doppler ultrasound examination revealed that the maximum
      blood flow velocity in the main portal vein increased from 14.0 +/- 4.5 cm/sec to
      48.0 +/- 16.5 cm/sec. The mean follow-up time in the successful cases was 4.5
      months (range 2-8 months). The shunt patency was determined with color Doppler
      ultrasound in 15 patients: occlusion in one and no accites in 4. Varices
      disappeared in 8 patients and became less evident in 7. No patients had
      recurrence of varices bleeding or encephalopathy during follow-up. The results
      suggest that TIPSS is a safe and effective method for portal decompression in the
      treatment of variceal hemorrhage, and that portal vein puncture is largely
      dependent on understanding the three-dimensional relationships between hepatic
      and portal veins. To achieve an adequate portal decompression, we recommend that
      a stent of 12 mm in diameter be used in severe cases.

PMID- 7805445
TI  - Effects of parathyroid hormone and estradiol on proliferation and function of
      human osteoblasts from fetal long bone. An in vitro study.
AB  - The effect of parathyroid hormone (PTH) (0.01 nM-10 nM) and 17 beta-estradiol
      (E2, 1 nmol-10 nM) alone or in combination on 3H-thymidine incorporation,
      alkaline phosphatase and adenylate cyclase activities were investigated in human
      fetal osteoblasts using serum-free monolayer primary cultures. The results showed
      that PTH inhibited cell proliferation while E2 promoted it. On alkaline
      phosphatase activity, PTH showed a complex results while E2 were slightly
      inhibitory. PHT-E2 combination suggested that E2 could alter the effect of PTH
      alone, also potentiated the anabolic and antagonize the catabolic effects of PTH
      on bone formation.

PMID- 7805447
TI  - Current studies on biological effects of low level internal irradiation.
AB  - The biological effects of relative low level internal irradiation were
      introduced. 1. Life span studies on carcinogenesis. Pacific Northwest Laboratory
      observed 3782 rats given a single inhalation of 239Pu O2 at initial lung burden
      ranging from 0.25 to 180 nCi. Significant life span shortening was found at lung
      dose > 8 Gy and it was indicated that the presence of a "possible" threshold of
      about 1 Gy for lung tumor formation. 2. Health effects of radon and its progeny.
      Both experimental and epidemiological survey were studied. The nominal
      probability coefficient (fatality) for the public and workers are 7.90 x 10(5)
      per mJhm-3 (2.77 x 10(-4) per working level month, WLM). 3. Health effects on 3H
      on postnatal brain development and neurobehavior, genetic effects, carcinogenic
      effects and adaptive effects of 3H were investigated. 4. Study on the effects of
      neuroendocrine system under low level irradiation of 75Se (Auger electron
      emitter) and 35S (beta-particles emitter). The results showed that the
      neuroendocrine system is very sensitive to small dose of internal irradiation.

PMID- 7805448
TI  - Radiation hormesis in relation to radiation protection.
AB  - A radiation-induced adaptive response has been convincingly demonstrated in a
      variety of cultured cells. It is associated with the activation of genes and the
      up-regulation of protein enzymes, resulting in a delay in cell-cycling and the
      opportunity to repair radiation-damaged DNA as a transient phenomenon. Just how
      the adaptive response operates in a multi-cellular organism is still obscure, but
      there is little or no evidence in rodents and the beagle dog of a shortening of
      lifespan after exposure to acute doses up to a few hundreds of mGy or after
      chronic daily exposure resulting in accumulated doses of up to a few Gy.
      Nevertheless there is an increase in both non-neoplastic and neoplastic diseases
      which need not be life-threatening. A prudent approach has been used by the ICRP
      in deriving a value for radiation-induced detriment at low doses from which to
      recommend individual dose and risk limits in their system of radiological
      protection. This is not to deny the possible existence of an adaptive response.
      However, in the opinion of the author, there is no overwhelming evidence to date
      which justifies the belief that exposure to low doses in the range of natural
      background up to a few tens of mSv reduces the incidence of radiation-induced
      cancer in a population composed of persons of all ages with a wide spectrum of
      diseases and with widely different sensitivities to radiation.

PMID- 7805449
TI  - Low level radiation risks in people.

PMID- 7805450
TI  - Radiation hormesis in cancer mortality.
AB  - This review of recent literature presents new concepts to evaluate radiation
      hormesis in cancer mortality. Using these interpretations cancer mortality rates
      were found to be significantly reduced following whole body exposure to low doses
      of either acute or chronic irradiation. The threshold dose, the zero equivalent
      point (ZEP), provides a definitive limit for public health safety limits in
      chronic exposures. The ZEP is useful for triage following acute exposures in
      nuclear disasters.

PMID- 7805452
TI  - The Third Sino-American Conference on Burns and Trauma. August 16-19, Guangzhou.

PMID- 7805451
TI  - MR imaging in patients with strabismus.
AB  - The patients with strabismus, including 8 with superior oblique paresis, 1 with
      inferior rectus paresis, and 1 with congenital constant exotropia, were examined
      with MR imaging at 1.5 tesla (T) or 0.5T with a surface coil. Abnormal findings
      of extraocular muscles were identified in 8 of the 10 patients and most of them
      were consistent with the clinical findings. Deviation of the optic nerves was
      noted in 5 patients. Coronal short repetition time (RT) and echo time (ET) images
      were used to measure the concerned extraocular muscles and the optic nerves. The
      differences in diameters between the concerned extraocular muscles of both the
      diseased and normal eyes were calculated. MR imaging is considered to be
      advantageous and can be favorably used to observe and measure the extraocular
      muscles and other intraorbital structures in patients with strabismus.

PMID- 7805453
TI  - Lymph node metastasis in stage I ovarian carcinoma.
AB  - One hundred and sixteen cases of stage I ovarian cancer from 6 hospitals in China
      were investigated for their lymph node metastasis from September, 1982 to April
      1991. Of them, 70 had epithelial tumor, 36 malignant germ cell tumor, 8 gonadal
      stroma, and 2 undifferentiated tumor. Ovarian tumor confined to one ovary (stage
      Ia) in 89 patients, both ovaries involved (stage IIb) in 6, and documented stage
      Ic in 21. Systemic lymphadenectomy involving all pelvic groups of node together
      with aortic lymph node was accomplished in 82 patients. In the remaining 34
      patients, pelvic lymph node dissection was performed. The incidence of lymphatic
      metastasis was 10.3% in this series. Serous cystadenocarcinoma was the most
      common lesion. All patients were followed up for at least half year. The
      mortality rate in patients with and without lymph node metastasis was 8.3% and
      2.8% respectively. The clinical significance of retroperitoneal lymphadenectomy
      in early ovarian carcinoma was discussed.

PMID- 7805454
TI  - Estrogen and progesterone receptors in normal cervix and primary cervical
      carcinoma.
AB  - Estrogen and progesterone receptors (ER, PR) were measured in 21 specimens of
      cervical cancer and in 17 specimens of normal cervix by monoclonal enzyme
      immunoassay (EIA). In normal cervix, 88.2% of specimens were ER-positive ( > 15
      fmol/mg protein), 74.5% were PR-positive ( > 15 fmol/mg protein) and 74.5% were
      both ER- and PR-positive. In cervical cancer, 66.7% were ER-positive, 42.9% were
      PR-positive and 38.1% were both ER- and PR- positive. There was no significant
      difference in ER status between the normal cervix and cervical cancer (P > 0.05),
      but PR status and levels in normal cervix were significantly higher than those in
      cervical carcinoma (P < 0.05). ER levels in squamous cell carcinoma was not
      correlated to the tumor stage, histologic grade and menopausal status. PR levels
      in premenopausal patients with squamous cell carcinoma were significantly higher
      than those in postmenopausal patients (P < 0.01). Adenocarcinoma of the cervix
      contained significantly more ER and PR than squamous cell carcinoma (P < 0.01, P
      < 0.05). In addition, serum E2 level was also assayed in 21 patients with
      cervical cancer. There was significant difference in E2 levels between the
      premenopausal and postmenopausal patients (P < 0.01). Patients were stratified
      according to E2 levels, a significant difference in PR levels and in the ratio of
      PR/ER was noted (P < 0.05, P < 0.01).

PMID- 7805455
TI  - Ionizing radiation-induced IL-1 alpha, IL-6 and GM-CSF production by human lung
      cancer cells.
AB  - A cell line derived from human lung cancer (AOI) was employed in the present
      study. A panel of cytokines were quantified by ELISA technique following cellular
      exposure to X-irradiation. Tremendous increase in the levels of both IL-1 alpha
      and IL-6 were observed, GM-CSF was also detected. A comparison of time kinetics
      of IL-1 alpha and IL-6 production was made with that of cell cycle progression
      which was determined by FCM BrdU/DNA bivariate analysis. No cell cycle specific
      changes were found. The biological implication of radiation-induced cytokine
      production was discussed.

PMID- 7805456
TI  - Discovery of extracellular multiple form of Chlamydia trachomatis in the tissue
      culture.
AB  - A strain of Chlamydia trachomatis was isolated from a patient with nongonococcal
      urethritis (NGU). Alternate passages between chick embryo and McCoy cell culture
      were examined. From the Giemsa stained coverslips taken from the cell culture 96
      hours after inoculation, we found, to our surprise, that elementary bodies (EBs)
      distributed over a large area, and several intact cells embedded in them. These
      pure EB particles are round, fairly uniform in size and often appeared in pair.
      According to their morphology, distribution, arrangement and relationship with
      host cells, they are not the remains after cell lysis or directly released from
      host cells. We considered that they consisted of EBs which continued to divide by
      binary fission after their release. The name "Extracellular Multiply Form" was
      designated and their formation mechanism was proposed. This discovery gives a
      great challenge to primary theory, i.e. Chlamydias are obligate intracellular
      prokaryotic parasites. If we can further reveal the law of their formation, it
      will be of great significance both theoretically and practically.

PMID- 7805457
TI  - Congenital perforation of the triangular fibrocartilage of the wrist.
AB  - The triangular fibrocartilages (TFC) of 136 wrist joints from 48 fetuses and 20
      infants fresh cadavers without any evidence of known deformity and injury were
      studied. Perforations of the TFC were found not only in infants (18.8%), but also
      in fetuses (25%). The difference between the incidences of the perforations in
      the two groups is not statistically significant (P > 0.05). Furthermore, we did
      not find that perforation of the TFC is correlated with either sex or side of
      wrists (P > 0.05). Histologically, the vascularity and cellularity of the TFC
      have no significant correlation with the absence or presence of perforation in
      it. We believe that, besides trauma, inflammation and degeneration, some
      perforations of the TFCs are congenital in origin, which all take the form of
      fissure and are located mainly in the radial half of the TFC.

PMID- 7805458
TI  - Low-dose cyclosporin A and Tripterygium wilfordii inhibited porcine intestinal
      allograft rejection.
AB  - The aim of this study was to evaluate whether Tripterygium wilfordii (TW) could
      be used as an immunosuppressant, and whether antirejection therapy with low-dose
      cyclosporin A (CsA) and TW was better than the treatment with large-dose CsA
      alone in intestinal transplantation in pigs. 100 cm intestines were transplanted
      by using two-step models. Four pigs which received large-dose CsA for 100 days
      and then were given TW survived 251.5 +/- 181.5 days; 2 of these died of
      pneumonia 92 and 97 days after the operations respectively. Five pigs which
      received low-dose CsA and TW for 100 days, then TW was the only drug used in the
      survival animals, survived 243.2 +/- 90.9 days; none of these succumbed to
      infection. All the grafts in those which were administered with low-dose CsA were
      destroyed by acute rejection at 12.4 +/- 2.6 days. These results indicated that
      TW had some immunosuppressive effects, and antirejection treatment with low-dose
      CsA and TW could be considered as an acceptable therapy in small bowel
      transplantation.

PMID- 7805459
TI  - An experimental trial of artemether in treatment of Pneumocystis carinii in
      immunosuppressed rats.
AB  - An immunosuppressed rat model was established by injecting cortisone acetate 25
      mg/rat twice a week for 4 weeks and 12.5 mg/rat for another 2 weeks
      subcutaneously. A development of Pneumocystis carinii pneumonia (PCP) was found
      at the end of the 6th week in all rats. These rats were injected intramuscularly
      with artemether at 100 mg/kg once a day for 5 consecutive days. All rats were
      necropsied at the end of the 8th week. The lung impression smears were stained
      with Gomori's stain, and Pneumocystis carinii cysts were counted. The
      ultrastructural changes of trophozoite, precyst and cyst were investigated by
      transmission electron microscopy on the 7th day after treatment.

PMID- 7805460
TI  - Percutaneous balloon mitral valvuloplasty. An observation of 50 patients.
AB  - Percutaneous balloon mitral valvuloplasty (PBMV) was successfully performed in 50
      selected patients with mitral stenosis by using Inoue pillow-shaped balloon and
      Inoue technique. The average diameter of balloon used was 26.9 +/- 0.9 mm. 90%
      (45/50) of cases had either double or single mitral commissura split. Of the rest
      5 cases, 1 had a mitral score 13 and 4 had a history of mitral valve
      commissurotomy. Totally they had a mean mitral valve area increase from 1.13 +/-
      0.32 to 2.21 +/- 0.43 cm2, left atrial pressure decrease from 31.8 +/- 9.3 to
      14.7 +/- 5.6 mmHg, left atrial diameter reduction from 44.9 +/- 7.7 to 37.4 +/-
      4.9 mm, and transmitral gradient decrease from 21.7 +/- 9.8 to 4.0 +/- 5.2 mmHg.
      Most patients had a obvious cardiac function improvement, especially in patients
      with mitral score of 8 or less. 30% patients (15/50) had a mild mitral
      regurgitation, but relieved 3-6 months after procedure. During one year of follow
      up, the majority of patients (16/20) were found in a good cardiac function,
      mitral area and the left atrial diameter, except in 4 patients with a high mitral
      score of more than 10. It is suggested that for patient with lower mitral
      morphological score and good general health, a larger diameter balloon might be
      suitable for effectively improving patient's symptom, but for patients with a
      previous surgical mitral commissurotomy, PBMV should not be selected.

PMID- 7805461
TI  - Smooth muscle tumors of the gastrointestinal tract. Expression of ras P21
      oncogene product and the association with clinicopathology.
AB  - Quantitative analysis of ras oncogene product P21 was performed on paraffin
      blocks from 55 smooth muscle tumors of the gastrointestinal tract by
      immunofluorescence and flow cytometry. No positive evidence for P21 was found in
      5 cases of normal smooth muscle tissues. Eight of 14 leiomyomas were P21 positive
      (57%) but all of them were lower expressed with fluorescence index (FI) < 1.25,
      whereas a total of 29 leiomyosarcomas and 12 potential malignant smooth muscle
      tumors were found to be P21 positive (100%), and the majority were overexpressed
      with FI > 1.25 (P < 0.005). ras P21 was overexpressed significantly in the tumors
      with mitotic counts of more than 1/10 high power field (P < 0.005). It was also
      overexpressed significantly as soon as the mild cytologic atypia of the tumor was
      found (P < 0.005). Five-year survival rate was significantly higher in the
      patients with lower-expression of ras P21 than those with overexpression (P <
      0.005). It was suggested that the expression of ras oncogene product P21 could be
      used as an objective parameter in distinguishing malignants from benigns and
      predicting the prognosis of the patients with smooth muscle tumors of the
      gastrointestinal tract.

PMID- 7805462
TI  - Combined therapy of captopril and spironolactone for refractory congestive heart
      failure.
AB  - It is traditionally considered that angiotensin--converting enzyme inhibitor
      (ACEI) and spironolactone could not be used simultaneously because of the assumed
      risk of hyperkalemia. However, despite ACEI therapy edema and congestive status
      remain in some of the patients with severe congestive heart failure (CHF). In
      order to seek an effective therapy for these patients, we observed the efficacy
      and safety of captopil plus spironolactone in patients with refractory CHF, with
      strict monitoring of renal function, serum and urine electrolytes and blood
      pressure (BP). Thirty-five patients with refractory CHF and New York Heart
      Association functional class IV without renal dysfunction, hypotension and
      hyperkalemia, whose plasma aldosterone (ALD) level in 88.6% of them was above
      normal value, were randomly assigned to group A (n = 16, captopril alone) and B
      (n = 19, captopril plus spironolactone) for a 4-week treatment. The dosage of
      both drugs was individually adjusted in time according to the results of serum
      potassium and renal function. The improvement in dyspnea--fatigue ratings,
      urinary volume and Na+/K+ ratio in group B was more significant than that in
      group A, and the plasma ALD level in group B decreased obviously while it
      remained high in group A after therapy. Two patients in group B who had had
      normal plasma ALD level with urinary Na+/K+ ratio > 1.0 before the therapy did
      not exhibit any clinical improvement. A strong negative correlation was found
      between plasma ALD level and urinary Na+/K+ ratio (correlation coefficient 
      0.689, P < 0.01). None of the patients had obvious hyperkalemia and
      hypoaldosteronism.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7805463
TI  - Left ventricular wall motion abnormalities in chronic mitral and aortic valvular
      disease.
AB  - Left ventricular wall motion was analyzed from the contrast ventriculograms of 42
      patients with mitral and aortic valvular diseases by the computer-aided 100
      chords centerline method. The results showed that ventricular wall motion was
      decreased in the anterobasal and mitral valve regions in patients with mitral
      aortic valvular diseases. In 15 patients, there were also other local ventricular
      wall motion abnormalities, which were located in the anteroapical and
      posterobasal regions. Almost all of the patients with ejection fraction(EF) less
      than 0.5 had diffuse or localized hypokinesis. Ventricular wall motion in
      patients who died from cardiac causes early after receiving valvular replacement
      was lower than that of survivors. Using Fisher's judgement method, a formula
      could be established to predict the early prognosis of patients with chronic
      valvular diseases after valve replacement.

PMID- 7805464
TI  - Utility of Albusure test in screening for early stage of diabetic nephropathy.
AB  - All diabetic patients should be screened for the early stage of diabetic
      nephropathy, because microalbuminuria has a great prognostic significance. The
      albusure test (AT), alatex agglutination nephelometric immunoassay, is a rapid
      and low cost test for the detection of microalbuminuria of 30 mg/L or more. We
      compared the results of AT and of radioimmunoassay (RIA) for urinary albumin to
      evaluate the clinical utility of AT using fresh urine samples from 74 diabetic
      patients without persistent proteinuria and from 11 healthy subjects. Urinary
      albumin levels measured by RIA were 6.0 +/- 2.3 mg/L in the healthy subjects,
      11.0 +/- 8.7 mg/L in the AT-negative group (n = 61), and 38.1 +/- 10.2 mg/L in
      the AT-positive group (n = 13). Using a cut-off value of 30 mg/L by RIA, the rate
      of coincidence between AT and RIA was 89.2%, although five subjects were false
      positive by AT, and three were false-negative. These results show that AT may
      provide a useful monitor microalbuminuria, a reliable early mark of diabetic
      nephropathy.

PMID- 7805465
TI  - Human papillomavirus in condyloma acuminata and other benign lesions of the
      female genital tract.
AB  - PCR was used to detect (HPV) in condyloma acuminata (CA), pseudocondyloma whose
      cause is unclear, and the other benign lesions in female genital tract. The
      results showed that HPV prevalence rate in CA was 98.2%, type 6 was in 11 was
      85.7%, and that in pseudocondyloma, cervical polyp, cervical erosion and chronic
      vaginitis was 40.4%, 76.2%, 77.3% and 16.0%, respectively. Even in normal vaginal
      tissue, there existed HPV subclinical infection. HPV prevalence rate in swabs
      from patient's underwears and normal vaginal tissues was 73.6% and 54.0%
      respectively. The investigation of estrogen receptor (ER) in CA tissue carried
      out by immunohistochemical method found that positive ER was achieved in most of
      CA, and few of normal vulvar tissues was found. This result indicated that the
      occurrence of CA is probably related to estrogen.

PMID- 7805466
TI  - The infectivity of gametocytes of Plasmodium falciparum from patients treated
      with artemisinin.
AB  - Twenty-seven patients with gametocytes of Plasmodium falciparum (PF) were divided
      into groups A, B, and C. A daily dose of 1200 mg artemisinin was given for 5 days
      to group A, a state dose of 750 mg of mefloquine to group B and a single dose of
      750 mg mefloquine combined with 45 mg primaquine to group C. After treatment, the
      gametocyte count was taken daily, and infectivity of the gametocytes to Anopheles
      dirus via membrane feeding was also studied. Results showed that in group A, the
      density of gametocyte and infectivity were significantly reduced on days 4, 7, 14
      and 21 after treatment; In group B, the gametocytes were significantly reduced on
      days 7, 14 and 21 and infectivity was significantly cut down on days 14 and 21
      after medication. In group C, gametocytes disappeared in 5 out of 9 patients with
      failure of infecting mosquitoes in all 9 patients on day 4 after treatment. These
      indicate that artemisinin can effectively influence the infectivity of
      gametocytes of PF. Artemisinin is much better in blocking the transmission of PF
      malaria than mefloquine.

PMID- 7805467
TI  - Motion sickness in mice and conditioned taste aversion.
AB  - Forty-eight male mice in 6 groups were studied. Conditioned taste aversion (CTA)
      in mice was produced by various motions including cross-coupled acceleration,
      rotation to two directions (with or without visual field) and linear
      acceleration. Deprived of water for 24 hours, the mice were exposed to motion
      immediately after drinking a novel solution, 0.15% saccharin. All groups received
      two pairings of CTA training related to motion. The results showed that both of
      cross-coupled and rotation produced frank CTA and former was far more obvious
      than the latter. In addition, motion with visual field had a trend to intensify
      sickness response.

PMID- 7805468
TI  - Computer-aided three-dimensional reconstruction and measurement of bony and
      membranous labyrinth.
AB  - We used three methods to reconstruct a same bony and membranous labyrinth by an
      image processing work station (IPWS). Three dimensional (3-D) models of the bony
      and membranous labyrinth were thus obtained. Different parts of the labyrinth
      were measured and the spatial relationship between the bony and membranous
      labyrinth was observed. Many 3-D parameters such as cochlear length, volume of
      different parts of the labyrinth, angles among the three semicircular canals were
      measured. The results of this experiment are useful in the study of the cochlear
      and vestibular function.

PMID- 7805469
TI  - [Pancreas transplantation in dogs, effect on the endocrine pancreas of pancreatic
      duct obliteration and the mode of pancreas preservation. Histological study by
      surface analysis in dogs].
AB  - The effects of organ preservation and of canal obliteration on the endocrine
      pancreas were investigated in three groups of dogs. A control group of 6 animals
      were used for the histological examination of the normal pancreas. Two randomized
      groups (A and B) of 7 dogs the caudal pancreas was autotransplanted; a fibrin
      glue was injected into the pancreas canals 28 days before organ removal. In the
      group A, each graft was rinsed in a Euro-Collins solution and immediately
      transplanted. In group B, each graft was rinsed and held in a preservation
      solution for 24 hours before transplantation. On histological slices the ratio
      between of the total surface area of Langerhans islets to the mean surface area
      of each islet was greater in the control group than in group A (p = 0.011 and
      0.023); the ratio was not significantly different between the control group and
      the group B (p = 0.334 and 0.099). The histological surface area study suggested
      that the mode of organ preservation affects the endocrine pancreas and that
      blocking the canals has little effect.

PMID- 7805470
TI  - [Intraperitoneal chemo-hyperthermia with mitomycin C. Development and in vivo
      study of tolerability in dogs].
AB  - Peritoneal carcinosis is relatively frequent in the clinical course of digestive
      cancers (48% in cases with invasion of the serous membrane). Despite various
      therapeutic strategies, prognosis is almost always unfavourable, survival after 6
      months is extremely rare. Because of the known in vitro anti-tumour effect of
      hyperthermia and its chemosensitizing effect during Mitomycine C therapy, we
      decided to develop a technique based on these two anticancer effects:
      intraperitoneal hyperthermia and intraperitoneal chemotherapy. Termed CHIP, or
      chemo-hyperthermia intraperitoneal, this new method could be used for the
      treatment of peritoneal carcinosis. We report here results of the necessary
      animal experimentation before such a method could be proposed for human
      anticancer therapy.

PMID- 7805471
TI  - [Perforation of a jejunal diverticulum].
AB  - An observation of jejunal diverticulum is reported by the authors. It concerned a
      woman 82 years old whose disease appeared as an acute white spread peritonitis
      complication. The delay brought to perform the operation made it impossible to
      save diseased. About that case is evoked the pathogeny of the diverticulum:
      congenital or acquired. In the case reported it was acquired, the proof resulting
      from the anatomy-pathology. The disease can appear under a chronicle form with a
      difficult diagnosis or under a single relevant form whose surgical treatment must
      be done without delay.

PMID- 7805472
TI  - [Non-invasive dynamic studies of the cervico-thoraco-brachial pathway. Anatomo
      clinical correlative study].
AB  - Based on a computer assisted analysis of the anatomic and biomechanic features of
      200 subjects, the authors propose a dynamic approach to the exploration of the
      cervico-thoraco-brachial pathway. Results are given for 70 healthy and diseased
      subjects. Ultrasonic evaluations of the arterial component, dynamic echography of
      the axillo-subclavian venous component, electrophysiology including conventional
      electromyography, somesthesic and motor evoked potentials, and advanced imagery
      provide a panel of complementary diagnostic techniques.

PMID- 7805473
TI  - [Giant appendiceal mucocele. Apropos of a case].
AB  - One case of giant appendiceal cyst secondary to obstruction is presented. The
      clinical feature is a pseudotumoral syndrome with the discovery of a cyst of the
      right iliac fossa by a pre-menopause woman. It is pre-operatively misdiagnosed as
      an ovarian cyst. Only an appendectomy is made for this benign lesion. The
      mucoceles of the appendix are rare, considered as an entity of macroscopic
      anatomy. The review of the literature allow us to recall the histologic
      classification of these lesions, their diagnostic patterns and their treatment.

PMID- 7805474
TI  - [Synovial osteochondromatosis. Therapeutic indications based on a histological
      classification].
AB  - The surgical treatment of synovial osteochondromatosis fluctuates between the
      desire of doing the most complete synovectomy to avoid the formation of new loose
      bodies, and the technical possibilities of realising it without compromising the
      stability and the expansion of the ulterior mobility of the articulation. The
      histological examination of 44 operatory pieces allow us to suggest a
      histological classification of 4 evolutive stages based on the aspect of the
      synovial and without taking into consideration the existence or not of loose
      bodies which can exist in all stages. The surgical operation should be large in
      the stage of full fluorescence, it can be limited in the regression stage. This
      evolutive diagnostic can be done through the histological examination of the
      biopsy obtained by arthroscopy.

PMID- 7805475
TI  - [Salmonella aortitis complicated by rupture. Diagnostic and therapeutic
      problems].
AB  - We observed a case of aortitis due to Salmonella in a patient with
      spondylodiscitis. Outcome was fatal despite resection and grafting, extensive
      drainage and adapted but unsuccessful antibiotic treatment. Based on the
      literature, suggested treatment for patients with spondylodiscitis includes extra
      anatomic bypass combined with resection of the infected tissue and adapted
      antibiotherapy. In these emergency cases, computed tomography is the most useful
      exploration and also gives the diagnosis of spondylodiscitis. It is also
      necessary to identify the infectious agent to adapt the antibiotics.

PMID- 7805476
TI  - [Radiological consequences of lumbar disk surgery. Evaluation by MRI after 3
      months].
AB  - Radiologic effects of the surgery for lumbar disc herniation: a study with MRI at
      the end of the third post-operative month. The results of patients operated for
      lumbar disc herniation are good in 83%, fair in 10% and poor in 7. The poor
      results are considered to be the consequence of post operative fibrosis. A
      prospective study in 67 patients has been performed to study the post operative
      appearance of the operated lumbar spine, three months after surgery. 45 days
      after surgery the recovery of patients was assessed by the score of Staufer and
      Coventry and patients were entered in the study independently of their clinical
      state. The MRI was performed at the end of the third month postoperatively and
      patient recovery assessed according to the score of Senegas and Lavignolle. All
      the clinical and radiologic data were statistically analysed... the chi-square
      test, a p. value less than 0.05 was considered statistically non significant. The
      correlation between the clinical recovery and the MRI was realized.

PMID- 7805477
TI  - [Treatment of complex open fractures of the limbs using home-made external
      fixators. Technical presentation].
AB  - For the external fixation of complex open fractures in Da-Nang, Vietnam, the
      authors developed a home-made fixator, based on the Orifix system. The model
      allows correction of axial deviations and may be used for lengthening procedures.
      Sufficient stability is obtained without the aid of any other device. Weight
      bearing and sometimes walking are possible. The first cases were successful and
      are reported here.

PMID- 7805478
TI  - [Celioscopic pelvic and para-aortic lymphadenectomy].
AB  - Because small volume lymph node metastases are difficult to recognize despite
      modern imaging techniques and since staging laparoscopy is costly and leads to
      important patient discomfort, pelvic then para-aortic lymph node endoscopic
      dissection has been introduced for staging gynaecological cancers. Since 1988, we
      have performed 110 pelvic and 17 para-aortic lymph node dissections using this
      technique. Pava-aortic endoscopic biopsy is indicated for advanced cancer of the
      cervix and subrenal biopsy for cancer of the ovary. Pelvic node dissection alone
      is useful in early stage cancers of the uterus and in cancers of the endometrium
      as well as in urological indications.

PMID- 7805479
TI  - [Leiomyoma of the rectum].
AB  - Most of the 150 leiomyomas of the rectum reported since 1872 were no larger than
      5 cm. The authors report 3 new observations of leiomyomas of the rectum measuring
      more than 5 cm. The diagnosis of leiomyoma is difficult. The physical examination
      and rectoscopy suggest a submucal tumour of the rectum and endoendoscopy helps,
      describe the relations with the urogenital tract and the sphincters. Due to the
      lack of distinctive pathology features of malignancy, a leiomyosarcoma cannot be
      totally eliminated. The prognosis is uncertain due to the rate of relapse and the
      short follow-up (less than one year) in the previously reported cases. A slow
      spontaneous clinical course is however possible. The treatment goal is complete
      surgical removal. While local exeresis is indicated in tumours less than 5 cm in
      size, echo-guided endorectal protectomy with or without amputation of the
      sphincter should be discussed for larger tumours.

PMID- 7805480
TI  - [Evaluation of quality of care in a general surgery department].
AB  - A permanent evaluation of a department's activity and the quality of health care
      it provides is needed to avoid inappropriate use resulting from a wide range of
      causes. The activity of a general surgery department treating and average of
      1,500 patients per year and performing 1,200 operations was analyzed over the
      period 1986 to 1992. Post-operative hospital follow-up was noted for each patient
      and any complications were analyzed on discharge day by the surgeons, the
      anaesthesiologists and the nursing staff. A year-end sum up was conducted each
      year by homogeneous groups. Examples are presented: surgery for cancer of the
      oesophagus (122 cases), surgery for gastro-oesophageal reflux (120 cases),
      thyroid surgery (1,314 cases from 1988 to 1992). Complications, hospital stay and
      former pathologies were evaluated in order to determine the indications, prevent
      complications and evaluate more rapidly the advantages of modifications in
      techniques. The results were compared between surgeons. This daily evaluation
      allowed a better analysis than a retrospective study compared with data in the
      literature. Permanent personal reevaluation was one of the practical consequences
      of the study considered to be and enriching experience.

PMID- 7805481
TI  - [Results of 81 supra-articular femoro-popliteal bypasses using PTFE].
AB  - The indications for supra-articular prosthetic bypass is still a controversial
      subject in cases where the internal saphenous vein can be used, or in stage II
      cases. These bypasses cannot be performed unless they are as permeable as venous
      bypasses and do not greatly increase the risk of exaggerating the symptomatology
      in case of thrombosis. In order to evaluate the outcome of these bypasses, we
      evaluated retrospectively our series of 81 surpa-articular femoro-popliteal
      prosthetic bypasses performed between 1987 and 1989. The man age of the patients
      was 64 years and 38% of them had coronary artery disease. Forty-six bypasses
      (57%) were performed in advanced stage II patients, 20 in stage III patients
      (25%) and 15 in stage IV (18%). Mean follow-up is 42 months. At 36 months,
      primary overall permeability was 65%. This level of permeability is in agreement
      with the data in the literature and is independent of the initial clinical stage,
      the downstream arterial network and the size of the prosthesis. The outcomes
      observed in our series would favour use of P.T.F.E. in the first intention
      operation to save the vein for possible subsequent use at stages III and IV.
      Inversely, for stage II, prospective randomized studies should be conducted in
      order to compare endovascular techniques and medical treatments.

PMID- 7805482
TI  - [Should the carpal tunnel be a subject of controversy? Apropos of the
      communication by G. Foucher--Session of 27 January 1993].

PMID- 7805483
TI  - [Endoscopic perforations of the colon. Apropos of 21 cases. Apropos of the
      communication by J. Hureau--Session of 9  December 1992].

PMID- 7805484
TI  - [Peroperative assay of parathyroid hormone 1-84. Is the unilateral approach under
      local anesthesia justified in surgery for primary hyperparathyroidism? Apropos of
      the communication by Y. Chapuis et al.--Session of 10 February 1993].

PMID- 7805485
TI  - [Carotid surgery under cervical plexus block. 405 consecutive operations].
AB  - There is controversy over the choice of anaesthesia for carotid surgery. The aim
      of this retrospective study was to report the early results of carotid surgery
      performed with loco-regional anaesthesia by blockade of the cervical plexus. From
      1987 to 1992, 405 consecutive operations on the carotid bifurcation were
      performed using this technique. Among these patients, 202 (50%) were
      asymptomatic, the indication being carotid narrowing of 80% or more, while
      clinical signs were observed in the other 203 patients (50%). According to the
      Sundt classification, 360 patients (89%) had a medical risk and 45 (11%) had a
      neurological risk. Occlusion of the controllateral internal carotid was present
      in 47 patients (12%). The deep blocade affected roots C2-C3-C4 followed by a
      superficial block using 0.5% Bupivacaine. An endarteriectomy was performed in 96%
      of the cases. In 10 (2.5%), there were complications or the cervical plexus
      blocade was insufficient: 6 caused the operation to be postponed and/or use of
      general anaesthesia, but none of these led to postoperative complication. In 35
      patients (8.6%) neurological events during clamping required establishing a shunt
      (6.1% and 27.6% in cases with permeable or occluded controlateral carotids
      respectively). Neurological recovery was rapid and complete except in 4 cases.
      There were 8 central neurological complications which persisted or appeared
      postoperatively: 5 regressive ischaemic events, 2 persistent ischaemic events and
      one which led to the patient's death. No cardiac complications were seen. We
      conclude that blocade of the cervical plexus is a simple and effective technique
      for surgery of the carotid bifurcation. With this method, detection of clamp
      intolerance is more reliable and it gives enough time for endarteriectomy. The
      risk of coronarian complications is low due to good haemodynamic stability. This
      method is a low-cost technique and is better adapted to understanding the
      mechanisms of neurological complications.

PMID- 7805486
TI  - [Colo-anal anastomosis with a colonic reservoir by mechanical sutures (video
      presentation)].
AB  - To remedy the loss of the rectal reservoir after resection of the rectum and colo
      anal anastomosis, Lazorthes et al. and Parc et al. have proposed adding a J
      shaped colic reservoir. The video describes the procedure performed entirely with
      mechanical sutures. The postoperative and functional results are briefly
      described.

PMID- 7805487
TI  - [Pancreato-gastric anastomosis after cephalic duodenopancreatectomy. Apropos of
      36 cases].
AB  - After pancreaticoduodenal resection, a pancreatic fistula is observed in 10% of
      cases with a mortality rate of 20-30%. The pancreatogastrostomy was evaluated as
      an alternative method of restoring pancreaticointestinal continuity. From 1989 to
      1991, 36 patients have undergone pancreatogastrostomy, after
      pancreaticoduodenectomy. The mortality rate was 2.7% (one pulmonary embolism).
      The morbidity rate was 2.7% (one pancreatic fistula). A endoscopic examination
      with injection of pancreatic duct was performed in 12 patients: in 9 cases we had
      a visualization of the anastomosis between the stomach and the pancreatic duct.
      These results confirm that pancratogastrostomy is a safe method of pancreatic
      drainage after pancreatoduodenectomy.

PMID- 7805488
TI  - [Technique of properitoneal hernioplasty. Unilateral reinforcement of the
      visceral sac with Mersilene giant prosthesis].
AB  - 358 hernias of the groin (340 patients), predominantly recurrent and re
      recurrent, were treated by this procedure, similar to bilateral hernioplasty,
      specifically developed for ambulatory surgery. There were 16 recurrences of which
      most were due to flaws in the original procedure. This was overcome by widening
      and extending the distal lateral corner of the mesh.

PMID- 7805489
TI  - [Thermic behavior of the petrous bone].

PMID- 7805490
TI  - [Histological study of the porous coating of the uncemented acetabulum. Apropos
      of 11 implants removed at autopsy].
AB  - Tissue ingrowth in the porous coating of 11 cementless acetabular components has
      been studied histologically. These cups were retrieved at autopsy from 8 patients
      who had undergone a primary total hip arthroplasty. Seven cups had a mean
      implantation period of 5.1 years, the other 4 had been in place for less than one
      year. This component was made of commercially pure (cp) titanium, with a porous
      surface of cp titanium fiber metal. The initial fixation of the cup was achieved
      by screws. The tissues of the porous coating were studied into 1 mm fields at
      four levels, and were categorized either as bone, marrow, cartilage or fibrous
      tissue. The fraction of void space within the porous coating occupied by bone was
      measured by backscattered scanning electron microscopy. The percentage of 1 mm
      fields with bony tissue was 20.9% and the fraction of void space occupied by bone
      was 12%. No regional significant difference was found. The number of fields with
      bone increased from the interface between the porous coating and the substrate of
      the cup to the interface between the outer surface of the porous coating and the
      host bone. All the screw threads were covered with lamellar bone. In the longest
      term cases, fine metallic and polyethylene debris were observed and their amount
      increased with time. This study showed that, despite the important variability in
      bone ingrowth, these cementless cups were able to give entire satisfaction to the
      patients.

PMID- 7805491
TI  - [Arthroscopy of the knee. Development of materials and ideas during the last 24
      years].

PMID- 7805492
TI  - [Tumor markers in the follow-up of colorectal cancers].
AB  - The aim of this work was to review the usefulness of tumour markers in the follow
      up of colo-rectal cancers after operation. The carcinoembryonic antigen (CAE) is
      the most sensitive marker for early detection of relapse. It can be combined with
      CA 19-9 assay, increasing the sensitivity and specificity of the tests. These
      assays are useful because one half of the relapsing tumours can be resected
      leading to a survival rate of 40%. CAE and CA 19-9 must be assayed within 2
      months to 2 years after surgery to be effective screening tests. Presently, the
      widespread use of labelled monoclonal antibodies can, in certain tests, localize
      recurrent tumours before a second look operations.

PMID- 7805493
TI  - [War wounds of the upper vena cava. Recovery after management from Sarajevo to
      Paris].
AB  - Penetrating chest injuries involving the superior veina cava are a seldom
      observed entity to our knowledge. Most often they cause death before the patient
      can reach a surgical facility; because of the exsanguination and a difficult
      surgical approach. The authors report a war-case of superior veina cava injury
      and have reviewed and analysed the literature concerning the issue of immediate
      intensive care and surgical approach of such life threatening injuries;
      especially in war conditions.

PMID- 7805494
TI  - [Variations of the right bile ducts. The futility of complete anatomical
      classifications].
AB  - Combination calculus shows that there is a considerable number of theoretical
      variations of the right ducts: [table: see text] Complete classification is
      therefore impossible, and the different frequencies of these variations in
      different series are easy to understand. Probably some of these theoretical
      distributions do not actually exist. A classification should be limited to a
      description of the mechanisms of variation (duplication and sliding on other
      ducts), to a list of the most frequent variations; dangerous distributions from
      the surgical point of view, even if they are exceptional, must be pointed out.
      Interesting conclusions can be reached when there is a significant difference
      between a theoretical and a practical frequencies. For the surgeon, an excellent
      cholangiography (in three dimensions if possible) is the key of his strategy.
      Direct approach of the vasculo-biliary sheaths is the key of a speedy and safe
      surgery: in a sheath the surgeon finds only the branches supplying the parenchyma
      entered by this sheath.

PMID- 7805495
TI  - [Multiple and recurrent cardiac myxomas. Is it a familial disease?].
AB  - From 1964 to 1992, 56 patients with cardiac myxoma have been operated on. Sixty
      seven operations have been made during which 85 myxomas have been excised. Five
      patients had been reoperated from recurrent myxoma: 4 patients 2 times, 1 patient
      one time. In this population we observe 7 cases of multiple myxomas implanted 7
      times in many cavities. The study of this series displays a lot of risk factors:
      implantation outside the left atrium, multiple myxomas in one or several
      cavities, true recurrence of myxoma, young age of the patient, associated lesions
      as part of the Carney's complex. In this series, 13 patients, representing 5
      families, have one or more of these risk factors. in two of them, a familial
      character has been demonstrated. Analysis of these special kinds of cardiac
      myxomas displays very closed analogy between familial myxomas and high risk
      group. These findings suggest that recurrent and/or multiple and/or familial
      myxoma represent the same entity.

PMID- 7805496
TI  - [Treatment of inguinal hernia by the Jean Rives technique. Replacement of the
      fascia traversalis by a Dacron prosthesis. Apropos of the reports of G.E. Wantz
      and E.P. Pelissier. Session of 12 May 1993].

PMID- 7805497
TI  - [Role of autoplasty in surgery for inguinal hernia. Apropos of the communication
      by E.P. Pelissier and D. Blum. Session of 12 May 1993].

PMID- 7805498
TI  - [Natural history of Crohn disease].

PMID- 7805499
TI  - [X-ray computed tomography in Crohn disease].

PMID- 7805500
TI  - [Indications of surgical treatment of Crohn disease].
AB  - Indications for surgery in Crohn's disease were studied in 100 consecutive cases.
      Cases included emergency situations (n = 22) complicated forms (n = 55) and
      chronic forms (n = 23). Lesions were located in the small bowel alone (n = 43),
      small and large bowel (n = 16) and in the colon and rectum (n = 16). During the
      same period, 26 reoperations were performed, there was no operative mortality and
      no short bowels were observed. A stomy was required in 30 cases and could be
      removed in 19. For lesions involving the small bowel, resections were limited to
      symptomatic lesions; long and short plasties were performed with no
      complications. For the colon, total and segmentary colectomy was performed for 18
      cases and ileorectal anastomoses in 13. Five proctectomies were required. Rectal
      exclusion was considered as a wait and see solution which was long in several
      cases with severe rectoperineal lesions. In these cases, secondary proctectomy
      should be widely proposed. For emergency situations, it would be prudent to use a
      safe operative technique with wide indication for stomies. For complicated forms,
      careful preparation allows for complete procedure with one operation. For chronic
      forms resistant to medical treatment, the decision can be rather difficult, but
      the fact that recurrences do exist should not mask the long-term remissions
      obtained in half the cases with surgery.

PMID- 7805501
TI  - [Prevention of recurrence in Crohn disease].

PMID- 7805502
TI  - [Influence of ano-perineal lesions on the outcome of the rectum in colonic and
      rectal Crohn disease].
AB  - Between 1960 and 1988, 83 patients (38 men, 43 women) underwent colectomy and
      ileorectal anastomosis (IRA) for severe colonic or rectal Crohn's disease. The
      mean age at IRA was 28.5 years. The mean interval from diagnosis was 4 years.
      There were two post-operative deaths. Among the 81 survivors 5 patients who had a
      covering ileostomy have never had their stomas closed and 24 patients required
      exclusion or excision of their IRA and rectum. (= 10 defunctioning IRA, 14
      proctectomies with definitive ileostomy). The mean interval between IRA and the
      creation of a permanent ileostomy was 4.1 years. The mean interval between the
      onset of problems following IRA and permanent ileostomy was 2 years. 25 patients
      had perianal lesions prior to IRA. 5 of these patients had unhealed perianal
      disease at IRA and 7 required defunctioning ileostomy (28%). The need for rectal
      excision or exclusion following IRA was not related to the presence of perianal
      disease prior to IRA but functional results were worse. 33 patients developed
      perianal lesions following their IRA, among whom 19 required exclusion or
      excision of the rectum. Failure of IRA was then significantly higher amongst
      those who developed lesions following IRA. Rectal preservation after IRA may be
      proposed with success to patients with a healthy rectum or with minimal or
      moderate proctitis, even if there is perianal disease that could be safely
      treated before IRA. In this last setting the patient has to be informed of the
      risk of rectal preservation and the possible risk of requiring ulterior
      protectomy.

PMID- 7805503
TI  - [Development of indications in surgery of coronary revascularization. Current
      role of mammary-coronary anastomoses].
AB  - At a time when the cardio-surgical community has become aware that arterial
      revascularizations are superior to venous bypasses, GRUNTZIG (24) initiated the
      now well-known, and highly successful techniques of endoluminal angioplasty
      (P.T.C.A.) thus leading many teams to explore non-surgical revascularizations.
      These fast changing events somewhat overshadowed the interest placed in arterial
      anastomoses in general, and in particular, in mammary-coronary anastomoses. We
      believe that in 1993, many centres have not used this technique to its fullest
      and propose to the Academie de Chirurgie a programme of operative indications
      reinstating mammary-coronary anastomosis to its proper place in the treatment of
      coronary artery disease.

PMID- 7805504
TI  - [Rotator cuff ruptures with predominant involvement of the subscapular tendon].
AB  - Among the all rotator cuff tears, the subscapularis lesions are quite rare. But a
      careful analysis leads to recognize them specially in case of antero-medial
      impingement between the coracoid process and the head of the humerus. This study
      of 25 observations where the rupture of the subscapularis was the predominant
      lesion, allows to emphasize some characteristics of them. The patients are often
      younger than for the other ruptures, a traumatic experience is not rare at the
      beginning of the history, the pain is usually the first symptom before the
      functional disability, the alterations of the rotator-interval and of the biceps
      tendon are very frequent, the arthroscanner is a very good help for the diagnosis
      and satisfying stitches are possible in case of early diagnoses. Lastly, the
      prognosis of these limited lesions is quite different than the one of very large
      cuff tears including the suscapularis tendon.

PMID- 7805505
TI  - [Global exposure of the lower extremity of the radius by extended external
      approach].
AB  - With classical lateral access to the lower radius, only the styloid process is
      correctly exposed and many surgeons prefer elective anterior routes, or more
      rarely posterior access. Our experience with posterior compression-extension
      fractures of the lower radius using a posterior plate has led us to describe the
      modalities of progression to the bone without injury to the tendons and vasculo
      nervous bundles. The technique described scrupulously avoids injury and also
      allows safe iterative access. Finally, and most importantly, this technique also
      exposes all the aspects of the bone. It can be successfully used for internal
      fixation in difficult cases and also for the treatment of former acquired or
      congenital deformations of the epiphysis. This route has been shown to be safe
      and successful in a prospective series of 187 applications of posterior plates
      for compression-extension fractures.

PMID- 7805506
TI  - [Toe transfers in traumatic mutilations of the hand in children. Solutions,
      techniques and results].
AB  - Severe mutilating injuries of the hand are rarely encountered in children. Among
      the reconstruction techniques, partial and total toe transfers are to be
      considered because these techniques fulfill the growth requirements and because
      good sensory results can be expected in children. A clinical series of partial or
      total toe transfers, performed for correction of post traumatic mutilations is
      presented. Clinical results and technical refinements are discussed.

PMID- 7805507
TI  - [Ideal total hip prosthesis in 1993].
AB  - Although it is a hazardous adventure to define what is an ideal in any field, it
      would appear that there is a certain consensus about total hip prostheses. The
      fundamental principle of the total hip replacement was based on the articulation
      of a spheric segment, a mobile head contained in a hemispheric non-retaining
      element. To date, the first material is a titanium in a alloy containing 6%
      aluminum and 4% vanadium. The second material facing the titanium is polyethylene
      or alumine. Thus the joint couple could be "polyethylene-metal", or "polyethylene
      alumine" or even "alumine-alumine". The hemispheric element can be a massive
      piece of polyethylene or formed by a peripheral metal (an open hemisphere) filled
      with the joint surface, itself made of polyethylene. This solution offers the
      possibility of changing the prosthesis in case of wear without interrupting the
      implant-bone contact. The first type is cemented to the bone with methyl
      polymethacrylate. With the second, the metallic part need not to be cemented and
      can be fitted to the bone by simple pressing. Several points are essential in the
      femoral piece. It should include a removable head so the length of the neck can
      be adjusted. It must fill the medullary canal as closely as possible and fill the
      methaphyseal space. It is fixed by a self-fitting system leading to stable
      secondary long-term fixation-a porous covering, sometimes with hydroxy apatite
      can also be useful. In certain cases it must be cemented, although the cement
      must only play the role of adaptation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7805508
TI  - [Celioscopic appendectomy. Survey of the French Association of Surgery].
AB  - When first described in 1983 by Semm, coelioscopic appendectomy had little impact
      on the surgical community. However, since 1988, the growing widespread use
      coeliosurgery has lead to renewed interest in the technique. A survey was
      conducted among the members of the French Association of Surgery. There were 303
      responses from 2,437 questionnaires: 195 concerned coelioscopic appendectomy and
      included a total of 11,086 cases. Most (55.9%) of the surgeons worked in private
      hospitals and had already gained experience with coelioscopy for gynaecological
      indications (56.4%). Programmed coelioscopic appendectomies had been performed by
      68.3% and peritonitis was the indication in 48.2%. The meso-appendix was treated
      with coagulation and/or a clip. Peroperative complications were observed in 132
      cases (1.19%). Conversion to laparotomy was necessary in 258 cases (2.33%). No
      deaths were reported. Postoperative complications were reported in 175 cases
      (1.58%). There were a total of 106 reoperations (0.95%); 43 times by repeat
      coelioscopy, 59 times by laparotomy and 4 times by Douglas puncture. Discharge
      was accorded 3.2 (mean) days after the operation. Coelioscopic appendectomy gives
      results comparable to the laparotomy technique. Its specific advantages are now
      being assessed in prospective studies.

PMID- 7805509
TI  - [Acute appendicitis and appendiceal peritonitis in children. Celioscopic
      treatment].

PMID- 7805510
TI  - [Plea for celioscopic appendectomy in acute appendicitis].

PMID- 7805511
TI  - [Insurance for the surgeon in cases of increased risk].

PMID- 7805512
TI  - [Acute appendicitis and appendiceal peritonitis treated by celioscopy in adults.
      Results of a survey with 4,214 cases: synthesis and conclusions].

PMID- 7805513
TI  - [Severe hemorrhage from gastroduodenal ulcer. Apropos of 100 cases].
AB  - Over a period of 7 years, 100 patients (70 males and 30 females; mean age 66
      years) were operated for digestive tract haemorrhage originating in an ulcer.
      There was a past history of ulcer in 21% and 29% had been taking drugs known to
      have a toxic effect on the stomach. Patent bleeding was observed by endoscopy in
      32% with clear arterial flow, or a visible vessel in 10. In 20 patients a fresh
      clot was observed. Surgery had been indicated for massive haemorrhage in 25
      cases, for persistent bleeding in 27, for recurrent bleeding in 37 and due to a
      visible vessel in 11. Conservative treatment was possible in three-fourths of the
      cases. Gastrectomy was performed in 26. Follow-up was uneventful in 55. There
      were 18 cases with complications and 27 deaths factors leading to fatal outcome
      and the data reported in the literature were analyzed.

PMID- 7805514
TI  - [Results of colo-anal anastomosis].
AB  - Fifty five cases of rectal resection with colo-anal anastomosis are reported.
      There were 51 cases of cancer and 4 cases of large villous adenoma. The mean
      distance between tumor and anal verge was 6.4 +/- 1.1 cm (2-8). The mean
      resection margin was 29.1 +/- 14.6 mm (0-60). The resection was macroscopically
      complete in 45 cases of cancer distributed as follows: Dukes stage A = 14, stage
      B = 12 and stage C = 19. Nine (16.4%) postoperative complications occurred; among
      four (7.3%) anastomotic fistulas, three were treated by colostomy prolongation
      and one by abdomino-perineal resection. Thirteen (28.9%) recurrences occurred, of
      which three (6.7%) were local recurrences. The actuarial five years survival
      rates was 63%.

PMID- 7805517
TI  - [Diabetes control and reduced diabetic long-term complications].

PMID- 7805515
TI  - [Injuries to the abdominal aorta during laparoscopy].
AB  - Member surgeons of the Societe de Chirurgie vasculaire de Langue francaise
      participated in a survey concerning traumatic injury to the aorta and
      retrospectively reported nine cases of injury occurring during laparoscopic
      operations. Six had occurred in 1991 when video-laparoscopic surgery was becoming
      widespread. The laparoscopy had been indicated as a diagnostic procedure in 4
      cases and for curative treatment in 5. Gynaecology disease were involved in 4
      cases and digestive diseases in 5. Injury was reported near the aortic
      bifurcation or at the origin of the common right iliac artery. Concomitant injury
      to the small intestine (1 case) and to the mesentery (n = 3) were also reported.
      No venous injury was observed. Haemodynamic collapsus was the presenting sign and
      occurred early in 6 cases and late in 2. In 1 case, the haemorrhage occurred
      during the laparoscopic procedure itself and in another blood loss was visualized
      through the needle. An unsuccessful and unneeded procedure had been performed
      before the diagnosis in 4 cases: on splenectomy, two mesenteric dissections and
      one subcostal laparotomy after cholecystectomy. In all cases, the vascular
      surgeon had been called in by the operating surgeon and most often operated via
      the xypho-pubien route. After clamping the aorta, the vascular lesions was
      sutured. There was one death, directly related to late diagnosis. The frequency
      of injury to the abdominal aorta found in the literature and the difficulties in
      diagnosis was recalled. Mortality has been reported to vary between 13 and 23%.
      Such complications demonstrate the need for a rigorous technique but do not
      counterindicate the continued use of laparoscopic procedures.

PMID- 7805516
TI  - [Aortic injuries in laparoscopy].

PMID- 7805518
TI  - [The changes in glucocorticoid receptors in peripheral leukocytes in asthmatic
      subjects].
AB  - The number of glucocorticoid receptors (GCR) in peripheral leukocytes was
      determined by radioligand-binding assay in extrinsic and intrinsic asthmatics.
      Their corresponding plasma cortisol levels were assessed. The results showed that
      the average number of GCR in asthmatics was significantly lower than that in
      healthy subjects (P < 0.01), and there was a linear correlation between the
      number of GCR and the course of asthma. Besides, there was also a linear
      correlation between the number of GCR and the age of the initial attack of
      asthma. No difference in plasma cortisol level was found between asthmatics and
      healthy subjects. These findings suggest that there is no primary and general
      impairment of glucocorticoid metabolism in the asthmatics, but the number of GCR
      in the asthmatics is lower than that in healthy controls. The decrease of the
      number of GCR in asthmatics, we think, is related to heredity and repeated
      attacks of asthma.

PMID- 7805519
TI  - [A study on the pulmonary amine imaging in asthmatic patients and guinea pig
      asthma models].
AB  - Scintigraphic technique (SPECT) with intravenous injection of 131I-HIPDM was used
      to study pulmonary amine imaging in asthmatic patients and Guinea pig animal
      models. The results showed that the patients and animals had similar
      characteristic changes of amine imaging: the amine scanning pictures were not
      well-distributed, pulmonary amine uptake was significantly decreased but the
      clearance speed significantly increased as compared with those in healthy
      controls (P < 0.05-0.01). The only difference between the patients and the
      animals was that the amine imaging parameters in animals during remission
      recovered practically to normal, while that in patients during remission did not.
      The mechanism and clinical significance of the above changes were discussed.

PMID- 7805520
TI  - [Protective effect of interleukin-1 receptor antagonist on oleic acid-induced
      lung injury].
AB  - Thirty-six mice were divided into a control group, lung injury group by oleic
      acid and protected group with interleukin-1 receptor antagonist (IL-1ra). There
      were 12 mice in each group. Oleic acid was injected into the tail vein of the
      mouse with a dose of 0.2 ml/kg to produce a model of acute lung injury (ALI). The
      result indicates that preadministration of IL-1ra to the mouse with ALI can
      decrease the lung index, lung wet-to-dry weight ratio and leakage of protein from
      pulmonary capillary, elevate PaO2, and significantly attenuate lung histologic
      injury (alveoli edema, alveoli hemorrhage, lung necrosis, inflammatory cell
      invasion). It is suggested that IL-1ra has protective effect on oleic acid
      induced lung injury and may be a potential tool for treatment of ARDS.

PMID- 7805521
TI  - [Radiofrequency transcatheter ablation of dual atrioventricular nodal reentrant
      tachycardia].
AB  - 24 cases of dual atrioventricular nodal reentry tachycardia (DAVNRT) were
      identified by EPS. Radiofrequency transcatheter ablation (RFCA) was applied to
      interrupt the slow pathways (SP) conduction with a large tip catheter in all the
      cases. The records from the ablation catheter in the first 8 cases were analysed
      retrospectively; a low amplitude, relatively slow spike ("B" wave) was found in
      all the successful cases. In the following 16 cases, "B" waves were purposely
      sought for the site of ablation, which was usually on the middle and proximal
      third of the line between His bundle and coronary sinus OS. AB interval was
      measured, it ranged from 35 to 65 ms with an average of 29 ms, being shorter than
      the AH interval. "B" wave usually followed the "jump" from the fast to SP, and
      was not eliminated by RFCA. As compared with the original ablation method, less
      energy (22.8 vs 26.1 W, P < 0.01) and shorter time of X-ray exposure were needed,
      if the RF current was applied at "B" site. During the ablation, A wave should be
      much smaller than V wave, in order not to damage the AVN. The appearance of
      junctional rhythm usually indicates a successful ablation of SP, SP were
      eliminated in all the 24 cases. After a follow-up of more than 2 months,
      recurrence was found in one patient, who underwent a second ablation. Complete AV
      block occurred in 1 patient, who had a pacemaker implanted. The presence of "B"
      wave possibly indicates the existence of a short pathway between the fast and SP.
      RF current applied at that site was safe and more effective.

PMID- 7805522
TI  - [Influence of cardiac structure, blood flow velocity and heart function on
      circulating atrial natriuretic peptide and renin-angiotension system].
AB  - Heart function and plasma atrial natriuretic peptide (ANP), plasma renin activity
      (PRA) and angiotension II (Ang II) were examined with echocardiography and
      radioimmunoassay in 9 patients with dilated cardiomyopathy (DCM), 41 with
      rheumatic heart disease (RHD), 29 with hyperthyroidism (Ht) and 24 normal
      subjects. ANP level was significantly increased as heart failure progressed (P <
      0.01 and 0.001). There was negative correlation between ANP and left ventricular
      fractional shortening, and between ANP and ejection fraction in DCM and Ht
      groups. There was positive correlation between ANP and maximal left atrial
      diameter, right atrial area, and diastolic diameter or volume of left ventricle
      in DCM and RHD groups, and negative correlation between ANP and peak flow
      velocity in aorta or through mitral valve in DCM group (r = -0.608, P < 0.05 and
      r = 0.710, P < 0.05). These findings suggest that the stronger the myocardial
      contractility and the faster the blood flow, the lower the plasma ANP level.

PMID- 7805523
TI  - [Preparation of digoxigenin labelled probe and detection of HBV DNA in liver and
      extrahepatic tissue with in situ hybridization].
AB  - A new rapid technique for intrahepatic and extrahepatic HBV DNA detection by
      using digoxigenin (dig) labelled probe with in situ hybridization was developed.
      This technique has the advantage of being non-radioactive and a quick procedure
      yielding stable results and showing a clear background. 45 liver specimens were
      tested with this technique. Among the patients with positive intrahepatic HBsAg
      and HBcAg, positive detection of HBV DNA was highest (77.27%, 17/22). Some
      results were confirmed by PCR test. 19 extrahepatic specimens were detected with
      in situ hybridization. HBV DNA was seen clearly in the nuclei of myocardial
      cells, pancreatic islet cell, renal tubule epithelial cells and testicular
      spermatogenic cells. The results of this study might contribute to the study of
      molecular mechanism of HBV-induced injury in liver cells and extrahepatic tissue.

PMID- 7805524
TI  - [The use of laser ignited mini-explosive technique in treating 100 cases of
      gastric bezoars].
AB  - The experience of breaking gastric bezoars endoscopically with a laser ignited
      mini-explosive head was reported. After successful application of this technique
      in vitro and in experimental animals, we began to use it clinically in January
      1988. In a period of more than four years, we treated 100 cases of gastric
      bezoars, 80 cases being male and 20 female, aged from 5 to 65 years. 70 cases
      were cured after one treatment, 24 after two and the remaining 6 cases after
      three times of treatment. The cure rate was 100%. Except one case complicated
      with gastric perforation, no other complications were observed. The etiology and
      prevention of gastric bezoars, as well as the new method and experience in
      treating this disease were discussed.

PMID- 7805525
TI  - [Insulin resistance and hypertension].
AB  - In this study, we have measured plasma glucose and insulin levels at fasting and
      following an oral glucose load (75g) in 39 non-diabetic subjects (22 untreated
      hypertensive, 17 normotensive subjects). We also assessed plasma cholesterol
      (Ch), triglyceride (TG) levels and Na(+)-K(+)-pump activity in the membranes of
      their erythrocytes. Overall, hypertensive subjects have hypercholesterol,
      hypertriglyceride, glucose intolerance and hyperinsulinemia. These changes
      accorded with Syndrome X proposed by Reaven. In multivariant analysis, after
      correcting for age, BMI, diastolic pressure (DBP) was positively related to
      fasting, 1/2h insulin and insulin area under cure (AUC) (P < 0.05). Both systolic
      pressure (SBP) and DBP were negatively correlated to Na(+)-K(+)-pump (P < 0.01,
      0.001), while Na(+)-K(+)-pump was negatively fasting, 1/2h, 1h, 2h insulin levels
      and insulin AUC (P < 0.05, 0.05, 0.01, 0.01, respectively). These results showed
      that insulin may affect Na(+)-K(+)-pump activity to develop hypertension
      independent of age and obese. We also postulated that insulin resistance was
      causal in the syndrome X, also one of factors developing coronary artery disease.

PMID- 7805526
TI  - [A clinicopathological study of 8 cases of Castleman's disease].
AB  - Castleman's disease (CD) is a chronic lymphoproliferative disorder characterized
      by presence of giant lymphoid masses. The clinical features and histopathologic
      findings of 8 cases of CD diagnosed according to the criteria described by
      Frizzera were reported. 2 were male and 6 female; their age ranged from 26-66
      years. Four patients with localized CD (three with hyaline vascular type and one
      with mixed type) had no systemic symptoms and had survived for a long time after
      surgery. Four patients with multicentric CD developed anemia, fever, elevated
      ESR, polyclonal immunoglobulinemia and manifestations of multisystem involvement.
      Steroids, chemotherapy, and radiotherapy had only resulted in partial remission
      in multicentric CD. The clinicopathologic differential diagnosis of CD from
      reactive lymph node hyperplasia in chronic infections, malignant lymphoma,
      connective tissue disease and angio-immunoblastic lymphadenopathy and the
      pathogenesis of CD were discussed.

PMID- 7805527
TI  - [Nitric oxide and diseases].

PMID- 7805528
TI  - [Idiopathic CD(4+)-positive T-lymphocytopenia].

PMID- 7805529
TI  - [Complications following Nd: YAG laser posterior capsulotomy].
AB  - We used neodymium-YAG laser to perform discissions of the posterior capsules in
      221 eyes of 203 patients who had undergone previous extracapsular cataract
      extractions. After a follow-up period ranging from 1-96 months, in the mean 10.5
      months, 47.06% of the eyes achieved corrected visual acuities of > or = 0.5. The
      complications included rhegmatogenous retinal detachment in 3 eyes (1.36%) and
      bullous keratopathy in one eye (0.45%). Although cystoid macular edema and
      glaucoma were not seen in this series, they had been reported. The author
      suggests that patients undergoing Nd: YAG laser capsulotomies require ongoing
      medical observations to detect and treat these complications.

PMID- 7805531
TI  - [Application of SRK II formula and measurement of A constant of KM intraocular
      lens].
AB  - The characteristics and distribution of the axial lengths and the results of
      keratometric measurements of 757 eyes with senile cataracts were reported and
      their relationship was discussed. The range of the axial lengths was 19.53-33.74
      mm, the mean value being 23.81 +/- 2.26 mm (mean +/- SD), the eyes with longer
      axial lengths accounting for 21.8% and the eyes with axial lengths over 27 mm,
      8.59%. The range of the degrees of the corneal curvatures was 39.75-50.50 D, the
      mean value being 44.47 +/- 0.78 D. The corneal curvatures of the eyes with
      shorter axial lengths are increased markedly with the shortening of the axial
      lengths. However, the corneal curvatures of the eyes with longer axial lengths
      are not decreased significantly with the lengthening of the axes. The A constant
      of KM intraocular lens we measured is 116.86 and the post-operative mean anterior
      chamber depth is 3.63 +/- 0.28 mm. If the C value is + 1.5 in eyes with 21-22 mm
      axial lengths, 0 in eyes with 22-24.5 mm and -0.5 in eyes with > 24.5, > 27, >
      28.5 mm, the predictive error seen post-operatively is the smallest.

PMID- 7805530
TI  - [Implantations of posterior chamber intraocular lenses in children with monocular
      cataracts].
AB  - Extracapsular cataract extractions with posterior chamber intraocular lens
      implantations were performed on 43 eyes with monocular cataracts in children
      including 35 cases of traumatic and 8 cases of congenital cataracts. 65.7% of
      eyes with traumatic cataracts and 25% of eyes with congenital cataracts achieved
      postoperative corrected visual acuities of > or = 0.5. It has been found that
      children have good tolerance to posterior chamber intraocular lens and no serious
      ocular complications, such as persistent uveitis, bullous keratopathy, or
      secondary glaucoma were seen. The main factors influencing the visual acuity are
      opacification of the posterior lens capsule and amblyopia. Their methods of
      prevention and treatment were discussed.

PMID- 7805532
TI  - [A long-term follow-up of the follow eye of unilateral wet senile macular
      degeneration].
AB  - The fellow eyes of 30 cases with unilateral wet age related macular degeneration
      (ARMD) were followed up for more than 5 years. On fundus and fluorescein
      angiographic examinations, it is demonstrated that a half of them showed normal
      fundi and the rest of them showed drusens and/or retinal pigment epithelial (RPE)
      changes. During the follow-up period, 4 cases developed subretinal neovascular
      membrane at the 5th, 6th, 10th, and 11th year, respectively. Of them, essentially
      normal fundi were in 2 cases, macular drusens in 1 case and RPE changes in
      another case at the first visit. The results indicate that the fellow eye of
      unilateral wet ARMD may develop subretinal neovascular membrane after a long
      period of time.

PMID- 7805533
TI  - [Surgical removal of macular epiretinal membrane].
AB  - Vitreous surgery was used to remove macular epiretinal membranes in 15 eyes of 15
      cases of which 7 were idiopathic and 8 secondary. In the period of postoperative
      follow-up, the visual acuity improved in 14 eyes (93%), in which 57% improved 3
      or more than 3 lines. The visual recovery is related to the time of operation
      chosen. No complication was noted, except development of a paracentral scotoma in
      1 eye.

PMID- 7805534
TI  - [A study on retinal light sensitivity of normal human visual fields].
AB  - The full threshold program of QZS-2 automated perimetry made in China was used to
      measure the retinal light sensitivity of the central 30 degrees and peripheral 30
      degrees-60 degrees visual fields of 111 eyes of 59 normal persons. Their ages
      ranged from 15-68 years and the average age was 38.4 years. From the
      corresponding respective comparisons of the results, it is shown that the mean
      light sensitivity of the macular, central 30 degrees and peripheral 30 degrees-60
      degrees visual fields between the left and right eyes has no statistical
      significant differences (P > 0.05), and there are also no statistical significant
      differences (P > 0.05) in the mean light sensitivity of the central and
      peripheral fields between the male and female subjects. The mean light
      sensitivity declines linearly with the increase of age and eccentricity. The mean
      light sensitivity of the central and peripheral visual fields decreases 0.6 dB
      and 0.7 dB, respectively, with each one decade increase of age. The mean light
      sensitivity also decreases by 2.6 dB per 10 degrees eccentricity. The mean short
      term fluctuation in the normal subjects is 1.39 +/- 0.56 dB.

PMID- 7805535
TI  - [Patterns of arteriovenous crossings in branch retinal vein occlusion].
AB  - The fundus color and fluorescein angiographic photographs of 82 eyes in 76 cases
      with recent branch retinal vein occlusion (BRVO) were compared with those of 82
      eyes in 82 cases without BRVO in the age-sex-matched control group to determine
      the relationship between the arteriovenous crossing and BRVO. It was found that
      90.3% of the crossings at the obstructive sites were located at the temporal
      quadrant, especially the superior temporal quadrant, and the artery lay anterior
      to the vein at the crossing in all of the eyes with BRVO (100%). In the 3
      subgroups of the control group, the rates of the crossing at the obstructive site
      with the artery lying anterior to the vein were 67.1%, 70.0% and 74.4% in the B,
      C and D subgroups, respectively. Each of the rate of the 3 subgroups was compared
      with that of the BRVO group, statistically. There were significant differences (P
      < 0.001). The results suggest that a crossing with artery lying anterior to the
      vein possibly be one of the risk factors of BRVO and the artery exerting
      mechanical pressure upon the vein be the main cause in the pathogenesis of BRVO.

PMID- 7805536
TI  - [Study and application of "binocular aniseikonia test chart"].
AB  - With the help of this chart, the image incongruity of simultaneous perception,
      fusion and stereoscopic vision can be precisely determined. It can objectively
      evaluate the binocular visual function and possesses important significance for
      the diagnosis and treatment of anisometropia, amblyopia, strabismus and visual
      fatigue.

PMID- 7805537
TI  - [Homoplastic keratomileusis for aphakic eyes with corneal leucoma].
AB  - We performed homoplastic keratomileusis on 6 aphakic eyes with central corneal
      leucoma. The results showed that the post-operative corrected visual acuities
      were markedly increased to 0.3-0.5 in 3 cases and to 0.1-0.2 in another 3 cases.
      Since such patients were neither indicated to undergo intraocular lens
      implantation or penetrating keratoplasty for various reasons nor indicated for
      epikeratoplasty, homoplastic keratomileusis can be chosen for them.

PMID- 7805538
TI  - [Modern methods of examination in the diagnosis of orbital neurilemmoma].
AB  - The important symptoms in 58 cases of neurilemmoma were slow exophthalmos and
      visual impairment. The diagnosis was discussed and the values of B-scan, CT and
      MRI were analysed.

PMID- 7805539
TI  - [A prospective study of maternal-infant transmission of Chlamydia trachomatis].
AB  - Direct immunofluorescent monoclonal antibody test was used for the examination of
      Chlamydia trachomatis at the cervices of 130 pregnant women and women after
      deliveries for 2-6 months with extragenital condyloma acuminatum and at the
      palpebral conjunctivae of their 102 newborns and infants. The results show that
      the rate of cervical infection in pregnant women is 4.92% and the rate of
      palpebral infection in the newborns 8.57%. After postnatal 2-6 months, the rates
      were markedly decreased both in the mothers and their infants, being 1.45% and
      0%, respectively. Chlamydia trachomatis infection is a new topic in modern
      perinatal medicine. In the report, the prevention of maternal-infant transmission
      problem was discussed.

PMID- 7805540
TI  - [Reactivation of latent virus in corneas of quiescent recurrent herpes simplex
      keratitis (HSK)].
AB  - By immunohistochemical staining, all 20 corneal half-buttons of HSK quiescent for
      4-60 months obtained from 20 cases undergoing penetrating keratoplasties were
      found negative of HSV-1 antigen. The other 20 corneal half-buttons were cultured
      for 3-4 weeks and 18 of them (90%) were found HSV-1 antigen positive. The 20
      reactivated corneal half-buttons were co-cultured for 1 week with primary rabbit
      kidney (RK) cells and cellular pathological lesions appeared in the RK cells in 3
      cultures which were also HSV-1 antigen positive. These results demonstrated that
      the latent virus might have been harbored in the corneal cells to escape
      immunohistochemical detection. In the view point of immunopathology and virology,
      penetrating keratoplasy can be performed on patients with HSK quiescent over 3
      months.

PMID- 7805541
TI  - [A cytological study of inhibition of secondary cataract with heparin].
AB  - Secondary cataract is caused primarily by migration and proliferation of
      fibroblasts on the posterior capsular surface after extracapsular cataract
      extraction. Human fetus skin fibroblast cell culture was used, by measurement of
      cell's life cycle, cellular DNA content, increase of cell number and density, to
      investigate the heparin inhibitory action on the growth of the cells. It is
      discovered that the growth rate of the fibroblasts is lowered in the culture
      medium with heparin and the inhibition takes place at the interval between G1 and
      S stage and at M stage of the cell's life cycle.

PMID- 7805542
TI  - [Studies on embryonal development of lamina cribrosa of human eyes].
AB  - The lamina cribrosa of 291 eyes were studied including 260 eyes taken from
      embryos and fetus of 7 weeks to full term and 31 eyes from infants under 1 year
      of age. From the observations, it is discovered that the development of the
      lamina cribrosa lags behind the development of the optic nerve. In the eyes taken
      from embryos or fetus < 4 months, only the ectodermal primordium of the lamina
      cribrosa is seen. The initial scleral part of the lamina cribrosa begins to be
      formed in the 5th month fetus. The fibrous tissue originating from the choroid
      and optic nerve sheath contributes the formation of the lamina cribrosa in the
      8th month fetus. At this time, the morphology of the lamina cribrosa is similar
      to that of an adult, but the thickness of the structure is still increasing till
      one year after birth.

PMID- 7805543
TI  - [A study on the structure of human lamina cribrosa sclerae].
AB  - The lamina cribrosa of 15 normal adult human eyes were observed by scanning
      electron microscopy and their images were analyzed by a computerized system to
      study the distribution of pores and the proportion of connective tissue in
      different regions of the lamina cribrosa. The results revealed that there are
      significantly more large pores (> or = 3,000 microns2) in the superior and
      inferior than those in the nasal and temporal quadrants, especially in the
      peripheral regions, however, in terms of area the percentages of connective
      tissue in the nasal and temporal quadrants are the highest. In addition, the
      histological study of the lamina cribrosa disclosed that the collagenous fibers,
      various in calibre, are arranged in bundles and tangentially around each pore.
      Since the nerve fiber damage in glaucoma initially occurs at the superior and
      inferior parts of the optic nerve, the above anatomical characteristics possibly
      can explain the cause of the visual field defects in early glaucoma.

PMID- 7805544
TI  - [Cysts of ciliary body epithelium].
AB  - Among 1352 eyes examined histopathologically, ciliary body epithelial cysts were
      found in 198 eyes. The cysts can be divided into 3 types: non-pigmented
      epithelial, pigmented epithelial and intra-epithelial cysts, the non-pigmented
      epithelial cysts being the most commonly seen. The former 2 types are formed by
      the proliferation of the inner and outer layer of the optic cup respectively and
      the formation of the latter one is related to the separation of the 2 layers of
      the cup. The cysts can be single or multiple, at most 14 non-pigmented ciliary
      epithelial cysts with 2 iris epithelial cysts being present in one eye. The
      incidence of ciliary epithelial cysts is as high as 14.6%. Because of the hidden
      position, clinical doctors seldom notice them. They can be misdiagnosed as
      melanoma, they can cause secondary glaucoma and localized cataract and they can
      be detached spontaneously. Therefore, clinical doctors ought to pay attention to
      this disease.

PMID- 7805545
TI  - [The dynamic changes in glutathione peroxidase activity and malondialdehyde level
      in experimental traumatic cataract in rabbit].
AB  - Glutathione peroxidase activity (GSH-PX) and malondialdehyde (MDA) level of
      experimental traumatic cataract in rabbit were determined at various intervals
      after needling. GSH-PX activities decreased in the lens after perforated trauma
      from 8 hours to 21 days, meanwhile the MDA level increased markedly. The results
      demonstrate that free radicals are involved in the formation of traumatic
      cataract.

PMID- 7805546
TI  - [The effect of acute and persistent ocular hypertension on ultrastructure in
      rabbit tissues of anterior chamber angle].
AB  - Sclero-circular compression operation was performed on 20 unilateral rabbit eyes
      to make a model of intraocular hypertension which persisted for 3 days, 1, 3 and
      4 weeks respectively in 4 groups of rabbits and another 4 rabbits were used as
      normal controls. The trabecular meshwork and aqueous plexus of the experimental
      rabbits' eyes were examined under transmission electron microscope on various
      post-operative days: 3 days, 1, 3 and 4 weeks. It was discovered that the corneo
      scleral and uveal trabecular meshworks were obviously distended and their core
      collagenous and elastoid fibers were hyperplastic, the phenomenon being more
      marked with the prolongation of the duration of the intraocular hypertension.
      Many endothelial cells were detached from the trabecular cords and freely located
      in the intertrabecular spaces. Persistent hyperplasia of collagenous fibers and
      accumulation of extracellular plague materials occurred in the endothelial
      meshwork, leading to its compactness. The giant vacuoles in the endothelial cells
      lining the inner wall of the canal of aqueous plexus were gradually decreased in
      number and the cytoplasm of the cells became attenuated and some fenestrations
      appeared. The results show that the main site of the resistance of the aqueous
      outflow occurring during intraocular hypertension is at endothelial meshwork and
      the above experimental morphological changes are quite similar to those of
      glaucoma patients.

PMID- 7805547
TI  - [An epidemiologic survey of blindness and low vision in persons over 45 years old
      in Doumen County].
AB  - An epidemiologic survey of blindness and low vision in persons over 45 years old
      in Doumen County, Guangdong Province was carried out in 1991. The sample size was
      932 subjects. We found that the impairment of vision < 0.3 accounted for 10.94%.
      The prevalences of bilateral blindness and low vision were 1.61% and 3.22%,
      respectively. Both the prevalences of blindness and low vision were increased
      with age. The leading cause of blindness was cataract (45.20%) and the second,
      corneal opacity (16.70%).

PMID- 7805548
TI  - Health-related quality-of-life assessment in medical care.
AB  - The concept of assessing health-related quality of life has a brief and vibrant
      history. In this monograph, theoretical issues related to the term and the
      reasons assessment of quality of life is important are discussed. There is a
      great deal of ambiguity surrounding definitions of the concept. This equivocation
      is caused in part by the fact that thinking on both the concept of health-related
      quality-of-life assessment and the way in which it should be measured are still
      evolving. Methodologic concerns regarding the assessment of health-related
      quality of life are discussed, including ways in which the validity and
      reliability of measurement approaches are established. These characteristics are
      important because they are necessary to ensure that accurate information is
      obtained with whatever instrument or procedure is used. Many significant issues
      relate to the use of quality-of-life assessment, and these are delineated.
      Consideration and resolution of these issues are prerequisites to the
      introduction of a given assessment instrument or procedure into a study. A large
      section of this article is devoted to a review of selected measures of health
      related quality of life. Three types of measures are discussed. The first type is
      referred to as general. These measures are designed to be used across different
      diseases, different treatments or interventions, and different groups of
      patients. The reliability and validity of general instruments or procedures, plus
      their history of empirical use, make them invaluable methods of measurement. The
      second type of measures is referred to as disease specific. These measures are
      designed to assess specific diagnostic or patient populations with the goal of
      detecting responsiveness or clinically significant changes. The ability to assess
      such changes in a particular patient population has led to major growth in the
      development and introduction of these instruments in the past few years. The
      final type of measure consists of batteries of separate instruments that are
      scored independently. The advantage of using this approach is that the battery
      can be put together to assess whatever aspects of health-related quality of life
      need to be measured. Examples of quality-of-life assessment in medical research
      include a discussion of how various procedures are used to measure the construct
      with asthma, chronic respiratory disorders, and human immunodeficiency virus
      (HIV) disease. All three types of assessment--general, disease specific, and
      batteries of measures--have been used in this respect. Newer methods of
      assessment, particularly disease-specific instruments and procedures, are also
      described.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7805549
TI  - [Reversal of malignant phenotype of human hepatoma cells by antisense c-ets-2, c
      myc and N-ras].
AB  - A recombinant retroviral vector was constructed which expressed antisense RNA of
      c-ets-2, c-myc and N-ras. The pseudotype virus was packaged and rescued by
      transfection in PA317 cells and used to infect human hepatoma cell line SMMC
      7721. After selection with G418, resistant colonies were obtained. Stable
      integration of retrovirus in infectants was shown by Southern hybridization of
      genomic DNA and the presence of antisense RNA was detected by RNA dot blot
      hybridization. It was demonstrated that the antisense RNAs did inhibit the growth
      of human SMMC-7721 hepatoma cells. The ability to form colony in soft agar and
      tumorigenicity in nude mice of SMMC-7721 were significantly suppressed by the
      antisense RNAs. The result implicates the potential value in future cancer gene
      therapy.

PMID- 7805550
TI  - [Establishment of immuno-PCR technique for the detection of tumor associated
      antigen MG7-Ag on the gastric cancer cell line].
AB  - The gastric cancer associated antigen McAb MG7-Ag was detected by means of a
      newly established method, termed immuno-PCR. A McAb-recombinant DNA chimeric
      molecule was made which possesses bispecific binding affinity for antigen that
      had been immobilized on microtiter wells and the segment of the attached DNA was
      amplified by PCR. The antigen of gastric cancer cell line KATO III was monitored
      by this method. Analysis of PCR products by agarose gel electrophoresis after
      staining with ethidium bromide allowed as few as 20 cells to be detected readily
      and reproducibly. Immuno-PCR showed a 10(4) enhancement in detection sensitivity
      compared with ELISA assay. When the same numbers of cells (2 x 10(6)/ml) were
      immobilized and then the serial diluted chimeric molecule was added, 3.8 x 10(
      14) moles and 3.0 x 10(-11) moles were needed to give positive results with the
      immuno-PCR and ELISA assay, respectively. Therefore, immuno-PCR could give an
      enormous amplification capability with good specificity, and has a sensitivity
      much higher than any existing techniques for antigen detection.

PMID- 7805551
TI  - [Enhanced metastasis of a mouse mammary adenocarcinoma after in vitro treatment
      with gamma-interferon].
AB  - gamma-Interferon (IFN-gamma) was detected by ELISA assay in ascitic fluid from a
      number of ovarian cancer patients. To study its clinical significance, the effect
      of IFN-gamma on the metastatic potential of a mouse mammary adenocarcinoma, MA
      891, was explored. Pretreatment of the tumor cells in vitro for 48hr with
      recombinant INF-gamma significantly increased the number of lung tumor nodules
      after i. v. or s. c. inoculation into (TA2 x 615) F1 mice. In contrast, when
      recombinant IFN-alpha pretreated MA-891 cells were likewise injected into mice
      significant decrease in metastatic potential was seen. The study in vitro
      indicated that pretreatment of the tumor cells with IFN-gamma but not with IFN
      alpha resulted in a decrease in susceptibility to NK cell cytotoxicity. In as
      much as both IFN-alpha and IFN-gamma can induce MHC class I expression on target
      cells. The increase in metastatic potential of IFN-gamma-treated tumor cells can
      be explained only partially on the basis of their reduced NK cells
      susceptibility.

PMID- 7805552
TI  - [Chronological characteristics of retinoic acid-induced HL-60 cell
      differentiation].
AB  - HL-60 cells can be induced to differentiate into mature granulocytic cells in a
      continuous exposure to all-trans retinoic acid (RA) for at least 96 h. In this
      study, RA was removed after being exposed to HL-60 cells for 12-96h. Then the
      cells were reincubated in a fresh medium without drug for additional 48-144h and
      their differentiation markers such as NBT reduction, morphological changes and
      cytokinetic characteristics were studied. The results demonstrated that once
      exposed continuously to 1.0 mumol/L RA for at least 48h, the HL-60 cells would
      proceed to terminal differentiation: about 60-90 percent of the cells became NBT
      positive, 40-80 percent of cells exhibited decreased nucleus/cytoplasm ratio and
      marked reduction in the number of nucleoli and displayed matured granulocytic
      morphology. Cytokinetic studies demonstrated 48-85 percent of cells arrested in
      G1 phase, which is typical for differentiated cells. However, if the cells were
      exposed to RA for less than 48h, they would not show differentiation phenotype.
      These results indicate that 48h exposure is critical for HL-60 cell
      differentiation induced by RA, and the cell differentiation induced by RA is
      irreversible and RA-independent.

PMID- 7805553
TI  - [Sequence of light chain variable region gene of a monoclonal antibody to human
      hepatocarcinoma].
AB  - The isolation of the rearranged immunoglobulin genes from a hybridoma cell line,
      which is a prerequisite for the construction of a recombinant antibody, can
      easily be achieved by PCR. We have determined the nucleotide sequence of the
      variable region of L chain of a high affinity monoclonal antibody HAb27 directed
      to human hepatocarcinoma. Analysis of the nucleotide sequence of the light chain
      V region of HAb27 revealed that the V kappa sequence was 85% identical to
      germline V kappa Ox1 sequence.

PMID- 7805554
TI  - [The relation between p53 expression and lymph node metastasis of breast cancer].
AB  - The monoclonal antibody to p53 and a rapid immunohistochemical method were used
      in this study to detect p53 expression in 50 paraffin-embedded breast cancers and
      7 benign hyperplastic diseases of breast. The results of immunostaining showed
      that 12 (24%) cases of breast cancers were positive and all benign lesions were
      negative. No significant difference was found between primary and metastatic
      sites of 11 paired samples of breast cancers in p53 expression, suggesting that
      the abnormal expression of had p53 occurred before lymph node metastasis of
      breast cancer. Statistical analysis revealed that the abnormal expression of p53
      was significantly correlated with lymph node metastasis of breast cancer (P <
      0.005) and also correlated with medullary breast cancer in which two of four
      cases strongly positive to p53 had lymph node metastasis. Our results indicate
      that the abnormal expression of p53 is not only involved in the development, but
      also involved in the metastasis of breast cancer. Therefore, detection of p53
      expression may have significant clinical importance in the evaluation of the
      tendency of lymphatic metastasis of breast cancer.

PMID- 7805555
TI  - [Effect of superoxide dismutase and diethyldithiocarbamate on the induction of
      squamous cell carcinoma of lung with methylcholanthrene in rats].
AB  - The squamous cell carcinoma of lung was induced with methylcholanthrene (MCA) in
      iodized oil in Wistar rats. During the development of the cancer, the animals
      were given superoxide dismutase (SOD) or its inhibitor diethyldithiocarbamate
      (DDC). In DDC group, 3 out of 50 rats developed cancer and 4 developed atypical
      hyperplasia of bronchial epithelium within 35 to 40 days. In SOD group, no cancer
      developed in all of the 52 rats, and only one had atypical hyperplasia in the
      lungs. Only one of 42 control rats had cancer and 2 rats had atypical hyperplasia
      of bronchial epithelium. The difference in cancer frequency between groups DDC
      and SOD was significant (P < 0.05). The results suggest that there is a synergism
      between DDC and MAC in the induction of lung cancer, while SOD can inhibit MCA
      induced lung cancer development. The mechanism of the effect of SOD and DDC was
      discussed.

PMID- 7805556
TI  - [An in vitro and in vivo study of antitumor effects of rHTNF-alpha on human
      ovarian cancer].
AB  - We examined the cytotoxic activities of recombinant human tumor necrosis factor
      (rHTNF-alpha) and five chemotherapeutic agents, CTX, 5-Fu, VCR, DDP, KSM, against
      two human ovarian cancer cell lines, OVCAR3 and CAOV3, using the MTT assay. The
      results showed that cytotoxicities of rHTNF-alpha at 5 x 10-5 x 10(4) u/ml
      against OVCAR3 cell line for 24 h exposure were from 14.2 +/- 6.8% to 67.2 +/-
      3.0%, and those against CAOV3 cell line were from 8.2 +/- 4.3% to 60.9 +/- 1.3%.
      The cytotoxic effects of all five chemotherapeutic agents against the two cell
      lines were much lower than that of rHTNF-alpha. Further, we studied the combined
      anticancer potential of rHTNF-alpha with chemotherapeutic agents against the two
      cell lines. Various degrees of synergism in cytotoxicities of DDP or KSM in
      combination with rHTNF-alpha were observed. The cytotoxic effect of rHTNF-alpha
      on CAOV3 cell were also morphologically observed under phase contrast and
      electron microscope. Based on experiment in vitro, the in vivo anticancer
      activity of rHTNF-alpha alone or in combination with KSM was examined against
      human ovarian cancer OVCAR3 subcutaneously transplanted in nude mice. After 8
      weeks of treatment, a statistically significant difference of mean tumor volume
      was found between the control group and groups that received rHTNF-alpha or rHTNF
      alpha plus KSM (P < 0.01).

PMID- 7805557
TI  - [NDPK/nm23 expression and its correlation with lymph node metastasis in human
      lung cancer].
AB  - Using labelled streptavidin-biotin (LSAB) method, we examined the expression of
      nucleoside diphosphate kinase(NDPK), the product of metastasis suppressor gene
      nm23, in human lung cancer. Of 88 patients tested, 48 (54.5%) showed positive
      staining. The positive staining rate was higher in adenocarcinoma (28/42, 66.7%)
      than in squamous cell carcinoma (20/46, 43.5%; P < 0.05). Higher incidence of
      positive staining was also found in squamous cell carcinoma without hilar or
      mediastinal lymph node metastasis (16/27, 59.3%) than in that with hilar or
      mediastinal lymph node involvement (4/19, 21.1%; P < 0.05). NDPK/nm23 was equally
      expressed in adenocarcinoma irrespective of lymph node status. In both cell types
      of carcinoma, expression of NDPK/nm23 was not correlated with tumor cell
      differentiation, nor was it correlated with the P-TNM staging. Our results
      suggest that NDPK/nm23 may play different roles in the pathogenesis and
      metastasis of human pulmonary squamous cell carcinoma and adenocarcinoma. Its
      expression levels are inversely correlated with lymph node metastasis in squamous
      cell carcinoma.

PMID- 7805558
TI  - [Detoxifying effect of lisheng-se on cisplatin and its relation to
      metallothionein induction].
AB  - The effects of Lisheng-Se (Seleninized wheat germ) on metallothionein (MT)
      induction, lethal systemic toxicity, nephrotoxicity, hemotoxicity and anticancer
      activity of cisplatin (CDDP), were investigated in mice. The systemic toxicity of
      CDDP was significantly reduced by preadministration of Lisheng-Se (P < 0.05 or P
      < 0.01). The protective effects were better than its inorganic form (Na2SeO3) and
      Bi (BSN), (0.05 < P < 0.1). The MT level in the liver, kidney, heart and tumor
      tissues of mice treated with one of those compounds was determined. The results
      show that the levels of MT induced by Lisheng-Se were significantly increased in
      liver and kidney (P < 0.01 and P < 0.05). It was just in conformity with the
      conclusion that the best protective effect appeared in the groups treated with
      Lisheng-Se. These results suggest that increased MT synthesis in the liver and
      kidney may be involved in the protective effects of Lisheng-Se tested on the
      lethal toxicity, nephrotoxicity and hemotoxicity produced by CDDP. The
      experiments also show that Lisheng-Se did not affect the anticancer activity of
      CDDP in vitro and in vivo, while the MT level was not increased in cancer (P <
      0.05), so Lisheng-Se might not only improve the therapeutic index of CDDP, but
      also did not cause drug-resistance of cancer cells.

PMID- 7805559
TI  - [A clinical trial of radioimmunoguided surgery for gastric cancer].
AB  - A clinical trial of radioimmunoguided surgery (RIGS) using 131I labeled
      monoclonal antibody (McAb) 3H11 and a portable gamma-detector Oncoprobe II was
      performed on 25 cases with gastric cancer in this study. The 25 patients involved
      in the study included 4 for intravenous administration of 131I-3H11, 19 for
      injection of 131I-3H11 into submucosa by endoscope and 2 for receiving
      radiolabeled normal mouse IgG by endoscope as control. The sensitivity in
      detecting tumor infiltrated gastric wall was 94.6%, the specificity was 96.7% and
      the accuracy was 95.9%. For the detection of metastatic lymph nodes, the
      sensitivity of RIGS was 99.2%, the specificity was 97.7% and the accuracy was
      98.8%. The results described above indicate that the RIGS system for gastric
      cancer is very promising for identification of the extent of tumor, metastatic
      lymph nodes and reasonable radical resection with higher curability and better
      life quality for patients.

PMID- 7805560
TI  - [Immunohistochemical study on diamine oxidase in mammary cancer and adenosis].
AB  - In recent years, an obvious increase of diamine oxidase (DAO) in both blood and
      tumor tissues has been reported In this assay we observed an increased content
      and distribution of DAO in mammary cancer and adenosis by immunohistochemistry.
      The results show that: 1. DAO staining was strongly positive in mammary cancer
      and the brownish granules were spread over the cytoplasm; 2. In the adenosis of
      mammary gland, DAO was positive or weakly positive, but those hyperplastic ducts
      in it appeared to be strongly positive and the brownish granules distributed
      spotted; 3. The normal mammary tissue presented weak positive or negative DAO
      reaction. These observations indicated that the malignant tumor and hyperplastic
      changes of mammary gland induce increase of DAO in the cells, and the higher the
      DAO content, the greater the possibility of malignant changes.

PMID- 7805561
TI  - [The clinical significance serum N-POMC level in lung cancer patients].
AB  - Serum N-POMC level of 103 cases of lung cancer were measured in our hospital. The
      results were as follows: The lung cancer group, 50.5%, of patienst has an N-PONC
      level above the normal upper limit. The percentages of the N-POMC levels above
      the normal limit in lung cancers, such as: squamous-cell carcinoma,
      adenocarcinoma, SCLC and undifferentiated carcinoma were 52.2%, 50.0%, 47.3% and
      57.1%, respectively. There was no statistically significant difference of N-POMC
      levels among these kinds of lung cancers, Eleven of 18 cases of SCLC patients in
      stage IIIb or IV, and 3 of 9 cases of SCLC patients in stage IIIa had N-POMC
      levels above the upper normal limit. Could serum N-POMC be one of the indexes for
      assisting the diagnosis and prognosis of lung cancer needs further investigation.
      Cases with carcinoid, thymoma and neurofibroma had higher N-POMC levels too. Six
      patients had Cushing syndrome.

PMID- 7805562
TI  - [Modulation effect of cimetidine on the production of IL-2 and interferon-gamma
      in patients with gastric cancer].
AB  - The modulation effects of cimetidine on the production of IL-2 and IFN-gamma by
      the peripheral blood mononuclear cells in 31 patients with gastric cancer and 32
      normal subjects were studied. Their T lymphocyte subsets were also assayed. The
      IL-2 and IFN-gamma activity in patients were significantly lower than that in
      normal subjects (P < 0.01). Cimetidine could significantly promote IL-2 and IFN
      gamma production. There was a significant negative correlation between OKT8
      subsets and the activity of IL-2 and IFN-gamma (P < 0.01). The results showed
      that cimetidine could be used as an adjunct in the treatment of advanced
      neoplasm.

PMID- 7805563
TI  - [Response rate of small cell lung cancer treated with CE-CAP alternating
      chemotherapy].
AB  - From Sep. 1989 to Dec. 1992, 122 evaluable patients with small cell lung cancer
      (SCLC) treated with chemotherapy combined with radiotherapy in our hospital were
      analysed. There were 95 men and 27 women. The age ranged from 20 to 70 years. All
      were proven by pathology or cytology. They all did not receive previous treatment
      and had a measurable mass. Of them, 83 patients had limited disease (LD) and 39
      extensive disease (ED). Using CE-CAP alternating chemotherapy, 48 LD and 27 ED
      were given two cycles, 35 LD and 12 ED four cycles. In this series, remission
      time was not evaluated because all patients received radiotherapy shortly after
      chemotherapy. Of 122 patients, 10 patients (8.2%) achieved CR, 89 (72.9%) PR, 18
      (14.7%) S and 5 (4%) P. The total response rate was 81.1% (99/122), which is
      higher than that of COMVP and PE-CAV regimens. The response rates were 80.0% and
      82.9% in two and four cycle groups, respectively. There was no significant
      difference between the two groups. The main toxicity observed was nausea,
      vomiting and bone marrow suppression, but were tolerated by the patients. In
      conclusion, CE-CAP regimen can be recommended as the treatment of choice in SCLC.

PMID- 7805564
TI  - [Hyperfractionated irradiation for non-small cell lung cancer (NSCLC)--a phase
      III clinical trial].
AB  - From Dec. 1990 to Aug. 1991, 109 patients with NSCLC were randomized into two
      groups. The first was treated by hyperfractionated irradiation (HF) with 1.15
      1.25Gy per fraction, twice daily (interval > or = 6 hrs between fractions), and
      total doses of 69.6 +/- 2.1Gy. The other was conventional irradiation (CF) with
      1.8-2.0Gy per fraction, once a day, and total doses of 63.9 +/- 1.1Gy. All but 11
      was included in the analysis. The results showed that HF, compared to CF, could
      improve immediate response rates in patients with squamous cell carcinoma or with
      tumor size of 3-6cm (P < 0.05). The comparison of 1 and 2 year survivals did not
      show significant difference, but 1 year local control rate was 47.3% in HF and
      29.1% in CF, P < 0.05. Further stratified analysis showed that the 1 and 2 year
      local control rates in patients of HF in stage I-IIIa were 54%, 28%; 39%, 13% in
      patients of CF in stage I-IIIa, P < 0.05. The 1 and 2 year survival rates in
      patients in stage I-IIIa were 64%, 32% in HF; 18%, 6% in CF, (P < 0.05). An
      assessment of acute and late toxicity showed no significant difference in
      incidences between the two groups. It is concluded that HF, compared to CF, can
      improve 1 and 2 year survival and local control rates of patients in stage I
      IIIa.

PMID- 7805566
TI  - Functional Aspects of Energy Metabolism in Neural Tissue. Papers from the ISN
      Satellite Symposium. Carcassonne, France, August 28-September 1, 1993.

PMID- 7805567
TI  - Strategies for the supply of lipid substrates during post-natal brain
      development: a tale of two tissues.
AB  - In the suckling neonate the source of lipid and other substrates for brain
      development is the mother's milk. The lactating mammary gland is a highly
      versatile organ which is able to utilize a range of substrates for milk lipid
      production including glucose and ketone bodies (for de novo synthesis),
      triacylglycerols and non-esterified fatty acids. The composition of the milk
      lipid alters with changes in the substrates available to the mammary gland. The
      neonate has to process the milk triacylglycerols to forms (ketone bodies, medium
      chain fatty acids) more suitable for extraction by the developing brain. The
      strategies employed to allow this flexibility in the lactating rat and its
      offspring are discussed.

PMID- 7805565
TI  - [On the method of hyperthermic chemotherapy by regional isolated perfusion for
      tumors of lower extremities].
AB  - From August 1990 to June 1993, 30 patients with osteosarcoma of lower extremities
      were treated with chemotherapy by hyperthermic regional isolated perfusion. There
      were 19 male and 11 female with a mean age of 21 (15-28) years. All of the tumors
      were located in the lower limbs: 20 on the femora, 9 on the tibiae and 1 on the
      fibula. Chemotherapy was going on for 60 minutes during hyperthermic regional
      isolated perfusion. Temperature was kept at 42 degrees C in deep soft tissue
      around the tumor during perfusion. The results showed that local edema of the
      limbs were reduced observably, tumors were shrunken and hardened after perfusion.
      Perimeter of the limbs were decreased and mobility of the limbs increased.
      Pathological examination indicated that all of the tumors responded well to the
      chemotherapy by perfusion and 90%-95% of the osteosarcoma cells were destroyed.
      Two cases were complicated with compression syndrome, and 1 with renal failure.
      The authors would suggest that hyperthermic regional isolated perfusion is an
      effective chemotherapeutic method in management of malignant tumors of limbs.

PMID- 7805568
TI  - Mitochondrial Ca2+ transport and the role of intramitochondrial Ca2+ in the
      regulation of energy metabolism.
AB  - The mitochondrial inner membrane of all mammalian tissues, including brain
      tissues, has specific active transport systems for the uptake and egress of Ca2+.
      The primary role of this transport system is to relay changes in cytosolic
      [Ca2+], which stimulates energy-requiring processes in the cytosol (e.g.
      secretion), into the mitochondrial matrix where it stimulates several key steps
      in energy production. Thus using the same second-messenger molecule, the latter
      events allow energetic homeostasis to be maintained under conditions of cell
      stimulation. This appears to be brought about by a co-ordinated enhancement of
      steps throughout the pathways of oxidative phosphorylation, including substrate
      supply to the respiratory chain by dehydrogenase activation, activation of the
      respiratory chain itself by a mechanism which appears to involve changes in the
      matrix volume, and also possibly activation of the ATP synthetase where the
      release of a specific inhibitory subunit has been proposed.

PMID- 7805569
TI  - Development of enzymes of energy metabolism in the neonatal mammalian brain.
AB  - The metabolic capability for the complete oxidation of glucose, i.e. aerobic
      glycolysis, is highly developed in the brains of neurologically mature
      (precocial) species at birth, whereas this activity is severely limited in the
      brains of neurologically immature (non-precocial) species such as the rat and
      human. The latter utilize a mixture of glucose and ketone bodies for synthetic
      and energetic activities and the advent of neurological competence associated
      with the capability for complete dependence on and oxidation of glucose must
      await the development of key enzymes such as the pyruvate dehydrogenase complex
      (PDHC). A similar relationship appears to exist with respect to the development
      of neurological maturity of different brain regions in a single species, the rat.
      The development of the enzymes of energy metabolism of neonatal rat brain will be
      discussed with respect to the energy fuels available to the neonatal brain. In
      particular mechanisms by which the PDHC develops in neonatal brain will be
      evaluated. Evidence suggests that this is due to a specific increase in enzyme
      protein in contrast to a general increase in mitochondrial activity.

PMID- 7805570
TI  - Glycolysis-citric acid cycle interrelation: a new approach and some insights in
      cellular and subcellular compartmentation.
AB  - In the development of an integrated approach to study metabolic compartmentation
      and regulation in brain, we have emphasized the importance, versatility, and need
      to exploit the recent methodological advances in (1) NMR spectroscopy, (2)
      primary cultures of neurons and glial cells, and (3) subcellular fractionation
      (especially brain mitochondrial isolation). The integrated approach has the
      advantage of being able to draw data and inferences based on some combination of
      results derived from in vivo, cellular, and subcellular studies. For example,
      some in vivo NMR data may suggest that an enzymatic step may be rate-limiting in
      a particular pathway. This information may be used to frame testable hypotheses
      and questions that can be investigated in experiments involving primary cultures
      of neural cells and subcellular fractions. Subsequently, the data from such in
      vitro studies could serve as the bases for constructing the hypothetical
      framework for predicting the regulatory role, in vivo, of the enzyme in the
      pathway. We have discussed the known as well as the as yet ill-defined facets of
      the cellular and subcellular aspects of the glycolysis-citric acid cycle
      interrelation and have attempted to illustrate how such an integrated approach
      could be applied to generate testable hypotheses for investigating the mechanisms
      concerned with metabolic compartmentation and regulation in brain. In the process
      of the illustration, we discuss some of the evidence in support of the general
      hypothesis that the transfer of reducing equivalents across the inner
      mitochondrial membrane plays a major role in mediating the coupling of the
      glycolytic flux to that of the citric acid cycle. We have given some indications
      as to how this hypothesis could be further investigated employing our approach.
      Moreover, we hope that other workers will find this integrated approach useful in
      designing multidisciplinary studies to investigate mechanistic issues related to
      this important theme.

PMID- 7805571
TI  - Sites and mechanisms of function-related changes in energy metabolism in the
      nervous system.
AB  - Traditional neuroanatomical and electrophysiological methods to localize
      functional activities in the nervous system focus on perikarya as the sites of
      activity. Metabolic mapping of local functional activity in the nervous system
      with the deoxyglucose method has directed interest toward the activity in
      neuropil. Studies of local glucose utilization (lCMRglc) indicate that energy
      metabolism is increased by functional activation mainly in terminal projection
      zones of activated pathways. Electrical stimulation of a pathway raises lCMRglc
      in the projection zones of the pathway in almost direct proportion to the spike
      frequency. For example, stimulation of the sciatic nerve produces frequency
      dependent metabolic activation in the dorsal horn of the lumbar cord, where the
      axonal terminals of the afferent pathway reside, with no apparent metabolic
      effects in the cell bodies of the pathway in the dorsal root ganglia. Functional
      activation of the hypothalamo-hypophysial pathway by salt-loading increases
      lCMRglc in the neurohypophysis, the site of the terminal axons of the pathway,
      but not in the paraventricular and supraoptic nuclei, where the cell bodies of
      origin of the pathway reside. Activation by hypotension of pathways to these
      nuclei from brain stem structures involved in baroceptor reflexes does, however,
      increase lCMRglc in these nuclei. Depolarization induced by electrical
      stimulation, increased extracellular K+, or opening of Na+ channels with
      veratridine stimulate lCMRglc in neural tissues, and this increase is blocked by
      ouabain, a specific inhibitor of Na+,K(+)-ATPase. Activation of this enzyme to
      restore ionic gradients across cellular membranes appears to trigger the function
      related increase in energy metabolism. The metabolic activation is the
      consequence not of the functional activity itself but of processes operating to
      recover from that activity.

PMID- 7805572
TI  - Studies on metabolic regulation using NMR spectroscopy.
AB  - The effects of hypoxia and hypoglycaemia on cerebral metabolism and calcium have
      been studied using multinuclear magnetic resonance spectroscopy. 13C MRS showed
      that severe hypoxia did not cause any further increase in metabolic flux into
      lactate seen in mild hypoxia, but there was a further increase in 13C labelling
      of alanine and glycerol 3-phosphate. These results are discussed in terms of the
      ability of lactate dehydrogenase to maintain normal levels of NADH in mild
      hypoxia, but not in severe hypoxia. We conclude that glycerol 3-phosphate and
      alanine may provide novel means of monitoring severe hypoxia whereas lactate is a
      reliable indicator only of mild hypoxia. 19F- and 31P NMR spectroscopy showed
      that neither hypoxia nor hypoglycaemia alone caused any significant change in
      [Ca2+]i. Combined sequential insults (hypoxia, followed by hypoxia plus
      hypoglycaemia), or vice versa, produced a 100% increase in [Ca2+]i, whereas
      immediate exposure to the combined insult (hypoxia plus hypoglycaemia) resulted
      in a large 5-fold increase in [Ca2+]i, with severe irreversible effects on the
      energy state. These results are discussed in terms of metabolic adaptation to the
      single type of insult, which renders the tissue less vulnerable to the combined
      insult. The effects of this combined insult are far more severe than those caused
      by glutamate or NMDA, which throws doubt on the current excitoxic hypothesis of
      cell damage.

PMID- 7805573
TI  - Glial swelling in ischemia: a hypothesis.
AB  - On the basis of experiments with primary cultures of mouse astrocytes with
      conventional K(+)-sensitive intracellular microelectrodes involving 'chemical
      ischemia' (antimycin a and sodium fluoride treatment), a model of ischemia is
      presented. According to this model, ischemia has no significant direct effect
      during the first 10 min on astrocytes; neurones, however, lose a major part of
      their K+ into the ECS. This leads to an astrocytic depolarization, which in turn
      activates astrocytic anion channels. This will result in passive, Donnan-mediated
      K+, Cl- and HCO3- fluxes into astrocytes, which in turn causes swelling and a
      collapse of the ECS. Arguments are put forward that this may explain the swelling
      of astrocytic endfeet, which occurs very early in an ischemic insult.

PMID- 7805574
TI  - Differential effects of serum protein(s) on substrate oxidation by isolated
      synaptosomes and cultured rat brain astrocytes.
AB  - This report extends the finding that serum protein(s) (0.5 mg/ml) caused a 50%
      decrease in the rate of glucose oxidation by dissociated brain cells with only
      marginal effects on the oxidation of other substrates. Since dissociated cells
      represent a heterogeneous population, studies were initiated to determine the
      effect of serum on the rates of substrate oxidation by isolated synaptosomes and
      cultured rat brain astrocytes. Experiments revealed that the addition of 5% serum
      v/v to the reaction mixture resulted in a decrease in the rate of 14CO2
      production from [6-14C]glucose by isolated synaptosomes by more than 70%. In
      contrast, the addition of 5% serum had little or no effect on the 14CO2
      production from [U-14C]glutamine by the synaptosomes and only marginal effects
      (20-25%) on 14CO2 production from [U-14C]lactate and 3-hydroxy[3-14C]butyrate.
      The effect of serum on the rates of substrate oxidation were similar for
      synaptosomal preparations obtained from adult animal brains or 18-day-old rats,
      except that with the latter preparation, 14CO2 production from 3-hydroxy[3
      14C]butyrate was more attenuated by the presence of serum than with the former
      synaptosomal preparation (50 vs. 25%). In contrast to the results with
      synaptosomes, the presence of 5% serum enhanced the rates of 14CO2 production
      from [6-14C]glucose, 3-hydroxy[3-14C]butyrate and [U-14C]lactate by 61, 35 and
      69%, respectively, in cultured rat brain astrocytes. However, this enhancement
      did not occur when the cells were grown in chemically defined media or when
      dibutyryl cAMP was added to the media.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7805575
TI  - Monitoring in vivo oxidation of 14C-labelled substrates to 14CO2 by brain
      microdialysis.
AB  - Cultured brain cells oxidize glucose and numerous alternate substrates to CO2 for
      energy production, however, the importance of these observations to the intact
      brain have not been established. We have adapted in vivo brain microdialysis
      procedures to measure the rate of 14CO2 formation from 14C-glutamate, 14C
      glutamine, and 14C-glucose in the hippocampus of awake unanesthetized free-moving
      rats. Two, 9 and 16 days after surgery (to implant guide cannulae) microdialysis
      probes were inserted into the guide cannulae and perfused with artificial CSF
      containing either 14C-glutamate, 14C-glutamine or 14C-glucose. Dialysate
      fractions were collected during 20 min intervals for determination of 14CO2. The
      amount of labelled 14CO2 increased for 40 to 60 min and then plateaued and
      remained relatively constant for at least 6 hours. When the probe was removed
      from the hippocampus and inserted into a vial containing non-radioactive CSF,
      14CO2 production dropped rapidly. The quantity of 14CO2 recovered from glutamate
      was greater than from glucose or glutamine reflecting pool sizes, uptake
      characteristics and point of entry into oxidative pathways. The microdialysis
      system was verified by using model systems with cultured astrocytes suspended in
      media to simulate the brain. The present results indicate brain microdialysis may
      be used to study the role of alternate substrates in specific brain regions under
      varying physiological states.

PMID- 7805576
TI  - Monitoring of glucose and lactate using microdialysis: applications in neonates
      and rat brain.
AB  - Methods for the continuous in vivo monitoring of glucose and lactate were applied
      in man for studies of peripheral metabolism and, in rats, for cerebral
      examinations. Lactate ('lactography') and glucose were continuously measured by
      the enzyme formation of NADH or NADPH using appropriate dehydrogenases. Glucose
      was monitored with a transcutaneous probe in neonates or with probes placed
      directly in the brain of conscious rats. In neonates a high correlation was seen
      between the dialysate and blood levels. A correlation between the age of the
      neonates and glucose levels in the dialysate was found, suggesting that the
      thickness of the skin determined to a large extent the diffusion of glucose into
      the probe. In the rat brain transient changes in the extracellular glucose levels
      were seen during electroconvulsive shock and immobilization stress. Lactography
      was applied to striatum or hippocampus during stress, electroconvulsive shock or
      systemic and intracerebral drug applications. Extracellular lactate decreased
      during intracerebral deoxyglucose infusion and was increased by excitatory
      neuronal activity and the presence of glucose in the perfusion medium. The
      present studies show that microdialysis in combination with continuous flow
      analysis can be used to study metabolic trafficking in vivo and in clinical
      studies. In the brain both neurons and glia may contribute to extracellular
      lactate levels.

PMID- 7805577
TI  - Functional aspects of creatine kinase in brain.
AB  - The distinct isoenzyme-specific localization of creatine kinase (CK) isoenzymes
      found recently in brain suggests an important function for CK in brain energetics
      and points to adaptation of the CK system to the special energy requirements of
      different neuronal and glial cell types. For example, the presence of brain-type
      B-CK in Bergmann glial cells and astrocytes is very likely related to the energy
      requirements for ion homeostasis (K(+)-resorption) in the brain, as well as for
      metabolite and neurotransmitter trafficking between glial cells and neurons. In
      contrast, the presence of muscle-type M-CK, found exclusively in Purkinje neurons
      which also express other muscle-specific proteins, is very likely related to the
      unique calcium metabolism of these neurons. In addition, the developmentally late
      appearance of mitochondrial CK (Mi-CK) during brain development indicates an
      important function for Mi-CK in the oxidative energy metabolism of the brain. The
      physiological importance of the phosphocreatine circuit fully operating in adult
      brain has been corroborated by recent data from in vivo 31P-NMR magnetization
      transfer measurements. Future investigations should concentrate on the possible
      involvement of CK in diseases of the CNS with altered energy metabolism, aspects
      of which are also discussed here.

PMID- 7805578
TI  - Functional maturation of creatine kinase in rat brain.
AB  - The physiological role of the phosphocreatine (PCr)/creatine kinase (CK) system
      has been studied in rat brain by comparing maturational changes in in vivo CK
      catalyzed reaction rate and activities of CK isoenzymes. The CK-catalyzed
      reaction rates, measured by 31P-nuclear magnetic resonance spectroscopy,
      increased 4-fold between 12 and 17 days of age. The mitochondrial CK (Mi-CK)
      isoenzyme, as a percentage of total CK, increased to the same extent over this
      relatively narrow age period. Cytosolic CK (B-CK) was active earlier and, with
      the total CK activity, increased steadily over a longer time course. An
      immunohistochemical study of cerebellum showed Mi-CK predominantly in gray
      matter, while the cytosolic CK was present in rather large concentrations in both
      gray and white matter. In the molecular layer, B-CK was most prominent in the
      Bergmann glial cells, while Mi-CK was more prominent in Purkinje neurons. During
      development a redistribution of Mi-CK from the Purkinje cell bodies to their
      processes was observed. These results point to regional differences in CK content
      and in isoenzyme-specific localizations. The increase in CK activity is
      temporally coincident with the maturational appearance of closely coupled
      decreases in brain PCr and ATP during hypoxia. These maturational changes suggest
      that the activity of the PCr/CK system, particularly the Mi-CK isoenzyme, is
      central in regulation of brain ATP.

PMID- 7805579
TI  - Cellular and subcellular compartmentation of creatine kinase in brain.
AB  - Creatine kinase (CK) catalyzes a reversible transphosphorylation reaction that is
      believed to play a crucial role in the maintenance and channeling of high energy
      phosphate in tissues with high energy demands. In rat brain development,
      cytosolic (nonmitochondrial) CK levels increase rapidly during the peak period of
      myelination and remain high in the adult. The cellular compartmentation of CK was
      investigated through the use of primary cultures of neurons, oligodendrocytes and
      astrocytes. The CK activity in cultured oligodendrocytes, which expressed both
      enzymatic and immunocytochemical markers of myelin, was the highest of the cell
      types examined and comparable to levels measured in whole adult brain; these
      observations suggest a role for CK in myelinogenesis. We found that low density,
      dividing astrocyte cultures also exhibited high B-CK (brain isoenzyme of CK)
      immunoreactivity, with the nuclear CK staining being especially intense. We
      studied these cultured astrocytes in more detail with respect to their intense
      nuclear CK immunoreactivity. Optical sections of astrocyte nuclei taken with a
      confocal microscope show that the high B-CK present is actually contained within
      the nucleus, with a nucleoplasmic distribution that does not co-localize with DNA
      or RNA. To ascertain whether the high nuclear B-CK in proliferating astrocytes
      correlated with ongoing cell division, we conducted experiments with confluent,
      nondividing cultures. These results show that both CK enzyme activity and
      immunoreactivity are high in the nucleus of proliferating astrocytes, and
      significantly reduced in the nucleus of quiescent, nondividing astrocytes. The
      high level of CK protein and activity in the nucleus of proliferating astrocytes
      suggests a role for CK in cell division/nuclear function.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7805580
TI  - Analysis of [1-13C]D-glucose metabolism in cultured astrocytes and neurons using
      nuclear magnetic resonance spectroscopy.
AB  - The metabolism of [1-13C]D-glucose by astrocytes, neurons and mixed
      astroglial/neuronal cultures derived from the striatum of fetal rats was studied
      using NMR. Metabolic activity was studied in resting and depolarized cells (55 mM
      K+), with dibutyryl cyclic-AMP added to the medium to promote cell
      differentiation, and with glutamate (0.1 mM) included in the medium. Due to
      sample limitations the accumulation of 13C label in metabolites within the cells
      was not sufficient to quantitate. Of the metabolites released into the medium by
      the astrocyte cultures and the mixed astroglial/neuronal cultures, measurable
      amounts of label were present in lactate C-3 and C-2, glutamine C-2, C-3 and C-4,
      acetate C-2, citrate C-2 or C-4 and C-3, glycerol C-1 or C-3, succinate C-2 or C
      3 and several unidentified metabolites. Of the labeled metabolites released into
      the medium, only succinate was markedly affected by K(+)-induced depolarization,
      dBcAMP, or glutamate. The label in succinate was increased, especially in the
      K(+)-depolarized astrocyte cultures (3- to 6-fold). The neuronal cultures
      consumed [1-13C]D-glucose much more slowly than the astrocyte cultures or the
      mixed cultures. Except for lactate C-3, there was no measurable 13C in
      metabolites in the medium of the neuronal cultures.

PMID- 7805581
TI  - Multinuclear NMR studies on the energy metabolism of glial and neuronal cells.
AB  - In this multinuclear NMR study myo-inositol is identified as a glia-specific
      marker for in vivo NMR studies. The unusually high inositol concentration may
      participate in the osmoregulatory system in astrocytes. Primary astrocytes also
      synthesize and export high amounts of hypotaurine, an intermediate of taurine
      synthesis. Taurine--another osmolyte--is synthesized from cysteine by astrocytes
      but not by primary neurons. Taurine as well as hypotaurine is accumulated by
      neurons from the extracellular medium. 13C NMR labelling results with 2-13C
      pyruvate indicate a considerable contribution of the anaplerotic pathway in
      primary neurons from rat. The activity is only half of the activity in primary
      astrocytes. The ratio of pyruvate carboxylase/malic enzyme activity versus
      pyruvate dehydrogenase activity reflects the degree of maturation. The 13C
      isotopomer ratio of glutamate and glutamine is different for pure astrocyte
      cultures. Therefore, the different isotopomer ratios of glutamate to glutamine
      obtained from intact brain studies alone do not prove TCA cycle compartimentation
      in the brain. Finally, the PCr/ATP ratio in primary astrocytes is 3 times higher
      than in primary neurons. This has to be considered in case of recovery from
      ischemic insults.

PMID- 7805582
TI  - Evidence for cooperativity between neurons and astroglia in the regulation of CO2
      fixation in vitro.
AB  - Increases in the extracellular potassium concentration which correspond to the
      increased potassium concentration seen with both normal and abnormal neuronal
      stimulation produce marked increases in the rate of CO2 fixation in astroglial
      cells in primary culture. This increase in CO2 fixation is seen only in
      astroglial cells; the low rate of CO2 fixation seen in the neurons did not
      respond to the increased potassium concentration. Cultures of astroglia and mixed
      astroglia-neurons were labeled with NaH[14C]O3 for 20 h to obtain material for
      preliminary identification of the labeled products of CO2 fixation in the
      extracellular and intracellular compartments. While both cultures had similar
      intracellular levels of labeled products (mainly amino acids), astroglial
      cultures released 4-fold more labeled products into the extracellular fluid.
      While labeled glutamine is a prominent product of astroglia, the bulk of the
      released labeled products are nonamino acids. These are presumably the products
      available to be recycled back to surrounding neurons (which cannot fix CO2) to
      replenish intermediates of the TCA cycle lost due to release of the
      neurotransmitters glutamate, aspartate and GABA.

PMID- 7805583
TI  - Neurotransmitters regulate energy metabolism in astrocytes: implications for the
      metabolic trafficking between neural cells.
AB  - In recent years a vast array of experimental evidence has indicated the presence
      of functional receptors for neurotransmitters on nonneuronal cells, in particular
      astrocytes. The two neurotransmitters vasoactive intestinal peptide (VIP) and
      noradrenaline (NA) exert profound, receptor-mediated, metabolic actions on
      astrocytes. Thus both neurotransmitters stimulate glycogenolysis in primary
      astrocyte cultures, with EC50s of 3 and 20 nM respectively. Astrocytes display
      basal glucose utilization rates ranging between 3 and 9 nmol/mg prot/min, a value
      that is remarkably close to glucose utilization of cerebral cortical grey matter
      as determined by the 2-deoxyglucose autoradiographic technique. NA markedly
      enhances glucose uptake and phosphorylation by astrocytes, with an EC50 of 1
      microM. The metabolic substrate that is released by astrocytes is predominantly
      lactate and not glucose. Since lactate can support neuronal activity and synaptic
      function in vitro, the possibility should be considered that glucose uptake by
      the brain parenchyma occurs predominantly into astrocytes which subsequently
      release lactate for the use of neurons.

PMID- 7805584
TI  - Portal-systemic encephalopathy: a disorder of neuron-astrocytic metabolic
      trafficking.
AB  - Portal-systemic encephalopathy (PSE) is a major neuropsychiatric complication of
      chronic liver disease. Neuropathologic evaluation of brain tissue from cirrhotic
      patients who died in hepatic coma reveals astrocytic (rather than neuronal)
      changes referred to as Alzheimer type II astrocytosis. Evidence to date suggests
      that Alzheimer type II astrocytosis is the result of ammonia neurotoxicity.
      Exposure of cultured astrocytes to concentrations of ammonia equivalent to those
      encountered in brain in experimental PSE results in Alzheimer type II
      astrocytosis as well as changes in other astrocytic parameters such as glial
      fibrillary acidic protein and glycogen metabolism. A second characteristic of PSE
      is the appearance of increased densities of 'peripheral-type' benzodiazepine
      receptors (PTBRs) in both brain and peripheral tissues. In brain, PTBRs are
      highly localized on astrocytic outer mitochondrial membranes. Experimental PSE
      resulting from portacaval anastomosis in the rat results in increased densities
      of PTBRs in brain and in increased expression of the endogenous PTBR ligand
      octadecaneuropeptide in nonneuronal elements. It is suggested that the PTBR and
      its endogenous ligands could mediate the astrocytic response to chronic exposure
      to ammonia in PSE. Astrocytic changes in PSE are accompanied by disruption of
      neuron-astrocytic metabolic trafficking. In particular, reuptake of the
      neurotransmitter glutamate into the perineuronal astrocyte is inhibited in PSE
      resulting in glutamatergic synaptic dysregulation and potentially compromised
      astrocytic energy metabolism. Astrocytic metabolism of monoamine
      neurotransmitters may also be increased as a result of increased activities of
      monoamine oxidase MAOB.

PMID- 7805585
TI  - Regulation of energy metabolism in synaptic terminals and cultured rat brain
      astrocytes: differences revealed using aminooxyacetate.
AB  - Several recent studies have demonstrated that the metabolism of energy substrates
      takes place in multiple compartments in both astrocytes and synaptic terminals
      from brain. There are a number of differences in the metabolism of astrocytes and
      synaptic terminals primarily due to the localization of key enzymes such as
      pyruvate carboxylase and glutamine synthetase in astrocytes. The present study
      determined the rates of 14CO2 production from several energy substrates by
      primary cultures of astrocytes and cortical synaptic terminals from rat brain.
      The rates of 14CO2 production from labelled substrates by astrocytes were 0.96 +/
      0.13, 11.13 +/- 0.67, 10.51 +/- 0.35, 24.92 +/- 1.66 and 4.80 +/- 0.50 for D-[6
      14C]glucose, L-[U-14C]lactate, D-3-hydroxy[3-14C]butyrate, L-[U-14C]glutamine and
      L-[U-14C]ma-late, respectively. The rates of 14CO2 production were also measured
      in the presence of 5 mM aminooxyacetate (AOAA) to determine the effect of
      inhibiting the malate-aspartate shuttle and other transaminase reactions on the
      oxidation of energy substrates. In astrocytes the addition of AOAA decreased the
      rate of glutamine oxidation 5-fold, consistent with other studies showing that
      glutamine enters the TCA cycle via transamination. AOAA increased the rate of
      14CO2 production from labelled glucose 4-fold, suggesting that inhibition of
      alanine biosynthesis profoundly alters the utilization of glucose by astrocytes.
      AOAA also increased the oxidation of lactate and 3-hydroxybutyrate 36 and 58%,
      respectively. The rates of 14CO2 production from labelled substrates by synaptic
      terminals were 13.12 +/- 1.05, 35.29 +/- 3.58, 17.66 +/- 1.95, 30.18 +/- 1.10 and
      9.95 +/- 1.29, respectively, for glucose, lactate, 3-hydroxybutyrate, glutamine
      and malate, demonstrating that all substrates were oxidized at a higher rate by
      synaptic terminals than by astrocytes. The addition of AOAA decreased the rate of
      14CO2 production from labelled lactate by 57% suggesting that the use of lactate
      for energy in synaptic terminals is tightly coupled to the activity of the malate
      aspartate shuttle. AOAA had no effect on the rate of 14CO2 production from
      labelled glutamine, demonstrating that exogenous glutamine enters the TCA cycle
      in synaptic terminals via glutamate dehydrogenase, not via transamination as is
      the case with astrocytes. AOAA had no significant effect on the rates of
      oxidation of glucose, 3-hydroxybutyrate and malate by synaptic terminals. These
      findings demonstrate that inhibiting transamination with AOAA had very different
      effects on the oxidation of energy substrates in the two preparations, suggesting
      that the regulation of metabolism is quite different in astrocytes and synaptic
      terminals.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7805586
TI  - Kinetics of 2-oxoglutarate uptake by synaptosomes from bovine and rat retina and
      cerebral cortex and regulation by glutamate and glutamine.
AB  - 2-Oxoglutarate (2-OG) is a metabolic precursor of glutamate and may be utilized
      to replenish the neurotransmitter pool. 2-OG is rapidly transported into neurons
      by a high-affinity carrier that is particularly prevalent in glutamatergic
      terminals. Here we report the kinetics of [U-14C]2-OG uptake by crude
      synaptosomal preparations from bovine and rat retina and brain, and the
      modulatory effects of glutamate and glutamine. In all four tissues, 2-OG uptake
      was mediated by a high-affinity system (Kt approximately 1 microM) that was
      subject to negative feedback control by glutamate and biphasic modulation by
      glutamine (another precursor of neurotransmitter glutamate).

PMID- 7805587
TI  - The nutritive function of glia in a crystal-like nervous tissue: the retina of
      the honeybee drone.
AB  - Among the variety of roles and diverse possible functions that have been
      attributed to glial cells, the nutritive function is strongly supported by direct
      experimental evidence obtained in a model of the honeybee drone retina. We have
      shown that in this nervous tissue, with crystal-like structure, in which glial
      cells and photoreceptor neurons constitute two distinct metabolic compartments,
      glial cells transform glucose to alanine and, with proline, fuel the mitochondria
      of the photoreceptors. Proline supplies the Krebs cycle by making glutamate. The
      use of proline implies high ammonia production. Pyruvate transamination in the
      glia fixes ammonia at a rate exceeding glutamine formation. We favor the
      hypothesis that ammonia rather than K+ is the metabolic signal trafficking
      between neuron and glial cells.

PMID- 7805588
TI  - Brain glutamate metabolism: neuronal-astroglial relationships.
AB  - The concentration of glutamate in the brain extracellular fluid must be kept low
      (approximately 3 microM) in order to maximize the signal-to-noise ratio upon the
      release of glutamate from neurons. In addition, the nerve endings require a
      supply of glutamate precursors that will not cause depolarization. The major
      precursor to neuronal glutamate is glutamine, which is synthesized in astrocytes
      and converted to glutamate in neurons. However, glutamine is not the sole source.
      Alanine also might serve as a precursor to glutamate via transamination, although
      this reaction is relatively inactive in synaptosomes. Finally, the branched-chain
      amino acids, and in particular leucine, appear to be very important precursors to
      glutamate and glutamine in astrocytes. By providing alpha-NH2 groups for the
      synthesis of glutamine, leucine also abets the uptake into brain of neutral amino
      acids, which are transported in exchange for brain glutamine. In addition, the
      branched-chain ketoacids are readily reaminated to the cognate amino acids, in
      the process consuming glutamate. Intraneuronal consumption of glutamate via
      ketoacid reamination might serve to buffer internal [glutamate] and to modulate
      the releasable pool.

PMID- 7805589
TI  - NMR spectroscopic studies of 13C acetate and 13C glucose metabolism in
      neocortical astrocytes: evidence for mitochondrial heterogeneity.
AB  - Neocortical astrocytes were incubated with 13C-labeled substrates to determine
      metabolic pathways. 13C NMR spectroscopy was used to analyze 13C incorporation
      into glutamine and citrate from the different precursors--[1-13C]glucose or [2
      13C]acetate. When glucose was the labeling substrate, incorporation due to
      pyruvate carboxylation should be observed in the C-2 position in glutamine and
      the C-4 position in citrate. A large incorporation due to pyruvate carboxylation
      was observed in glutamine in the C-2 and C-3 positions, but not in citrate. When
      acetate was the precursor, the labeling ratios in the C-2/C-4 positions in
      glutamine and in the equivalent positions in citrate were 0.27 and 0.11,
      respectively. Moreover, acetate labeled lactate in the C-2 position much less
      than did glucose. Altogether, these observations led to the conclusion that
      glutamine precursors and citrate are either produced in different types of
      astrocytes or in different tricarboxylic acid cycles, situated in functionally
      different mitochondria in the same cell, and that in all likelihood pyruvate
      carboxylase is expressed differently in these mitochondria.

PMID- 7805590
TI  - Glutamate and glutamine metabolism and compartmentation in astrocytes.
AB  - Metabolism of glutamate and glutamine in cultured mouse cerebral cortical
      astrocytes has been investigated using either radioactively labelled (14C) amino
      acids or 13C-labelled amino acids combined with NMR spectroscopy of cell extracts
      and lyophilyzed incubation media. Using [U-13C]glutamate it has been shown that
      in astrocytes exogenously supplied glutamate is primarily (70%) metabolized
      oxidatively through the tricarboxylic acid (TCA) cycle and to a lesser extent
      (30%) directly to glutamine. Glutamate metabolized in the TCA cycle is to a large
      extent recovered as lactate showing that the astrocyte-specific enzyme, malic
      enzyme is functionally active. Incubation with [U-14C]glutamine led to a higher
      specific radioactivity in glutamate than in glutamine. It could also be shown
      that glutamate and glutamine were metabolized differently to aspartate and
      alanine. These results taken together strongly suggest that glutamate/glutamine
      metabolism in astrocytes is compartmentalized and a model with multiple
      cytoplasmic and mitochondrial compartments of these amino acids is proposed.

PMID- 7805591
TI  - Utilization of glutamine and of TCA cycle constituents as precursors for
      transmitter glutamate and GABA.
AB  - In the present review evidence is presented that (1) glutamine synthesis in
      astrocytes is essential for synthesis of GABA in neurons; (2) alpha-ketoglutarate
      in the presence of alanine (as an amino group donor) can replace glutamine as a
      precursor for synthesis of transmitter glutamate, but maybe not as a precursor
      for transmitter GABA; (3) differences exist in the intraneuronal metabolic
      pathways for utilization of alpha-ketoglutarate plus alanine and of glutamine,
      and (4) alanine also functions as a substrate for oxidative metabolism in
      glutamatergic neurons. It should be emphasized that the supply of precursors for
      transmitter glutamate and GABA in glutamatergic and GABAergic neurons depends on
      metabolic processes in astrocytes regardless whether glutamine or alpha
      ketoglutarate plus L-alanine function as the transmitter precursors. The key
      reason that an interaction with astrocytes is essential is that both pyruvate
      carboxylase, the major enzyme in the brain for net synthesis of tricarboxylic
      acid cycle intermediates, and glutamine synthetase, the enzyme forming glutamine
      from glutamate, are specifically located in astrocytes, but not in neurons.

PMID- 7805592
TI  - Endoscopic view of antrochoanal polyp appearing as a large oropharyngeal mass.

PMID- 7805593
TI  - Singing dysfunction following vocal fold hemorrhage: the need for caution.

PMID- 7805594
TI  - Beach sand in the ear.

PMID- 7805595
TI  - Facial nerve neuroma.
AB  - Facial nerve neuromas are uncommon, slow-growing neoplasms that may occur
      anywhere along the course of the facial nerve from the brainstem to the facial
      muscles. The signs and symptoms are characteristic and vary with the anatomic
      site of origin. Surgery should not be attempted until a complete and thorough
      diagnostic examination has been completed. The surgeon should be prepared to
      perform a middle-cranial fossa or translabyrinthine approach in all cases, and
      must expect to do a nerve graft. The results of 37 patients treated by the author
      reveal that, under optimal conditions, patients who have had a facial nerve
      graft, can be expected to regain an average of 80% facial nerve strength in
      almost every case. All patients who have had a facial nerve graft will have some
      degree of synkinesis. No graft was required in 3 patients, and a hypoglossal
      facial anastomosis was used for one. Facial function was completely normal in 2
      patients, 16 had 80-90% return, 5 patients had 50-80% return, 4 had 20-50%
      return, one had no recovery at all and 9 recent patients have not reached the
      time for their expected recovery. Early diagnosis, prompt surgical removal and
      VII-VII Nerve graft for facial paralysis of ten or fewer years duration offers
      patients the best opportunity to avoid a permanent facial palsy.

PMID- 7805596
TI  - The use of video in ENT endoscopy: its value in teaching.
AB  - Videography is the most practical and effective method of documenting and
      teaching ENT endoscopy. Videography allows: (1) documentation of anatomy,
      physiology and pathology of deep structures of the ear, nose and throat; (2)
      teaching of delicate surgical procedures such as functional endoscopic sinus
      surgery (FESS), laryngeal surgery, and other endoscopic procedures; (3)
      instantaneous production of high quality hard copies of video images for teaching
      and patient records; (4) instant replay and repeated viewing by a slow motion or
      frame-by-frame analysis; (5) simultaneous viewing by a small or large audience;
      and (6) image digitalization for storage in the computer for later analysis. The
      author describes the value of videography in ENT endoscopy, namely video
      otoscopy, video rhinoscopy and videolaryngoscopy. The use of video in endoscopy
      will continue to play a vital role in Continuing Medical Education (CME).

PMID- 7805597
TI  - Surgical treatment of Meniere's disease.
AB  - Surgical treatment is used only for patients with Meniere's disease in cases that
      do not respond to medical therapy. At the present time, the endolymphatic sac
      shunt operation is performed in cases where the auditory threshold is fluctuant
      around 30 dB. When the auditory threshold is between 40 and 70 dB we use the
      vestibular neurectomy by the retrosigmoid approach. In patients with Meniere's
      disease with profound hearing loss the translabyrinthine neurectomy is used. The
      advantages of the vestibular neurectomy by the retrosigmoid approach compared to
      the retrolabyrinthine and middle fossa approaches will be described.

PMID- 7805598
TI  - Benign positional vertigo produces a specific pattern of abnormalities with high
      frequency vestibulo-ocular reflex testing.
AB  - The vestibulo-ocular reflex was studied at high frequencies of active head
      rotation (2 to 6 Hz) in twenty-three patients with benign positional vertigo
      (BPPV). Gain and phase measurements were obtained in the vertical and horizontal
      planes, and the results were compared to those of a control group consisting of
      19 asymptomatic age-matched subjects. In the horizontal plane, the phase lead was
      significantly smaller in patients with BPPV as compared to controls (p < 0.01 at
      all frequencies). Vertical results did not differ from normals. These findings
      challenge "cupulolithiasis" as an explanation of the mechanism of BPPV's
      symptoms.

PMID- 7805599
TI  - Malignant otitis externa in AIDS patients: case report and review of the
      literature.
AB  - Malignant otitis externa is a necrotizing infection of the external ear canal and
      surrounding soft tissue and bone, usually caused by Pseudomonas aeruginosa. The
      infection classically occurs in diabetic patients, however recently, several
      patients with the acquired immunodeficiency syndrome (AIDS) have been reported to
      have malignant otitis externa. A patient with AIDS who had malignant otitis
      externa with skull base osteomyelitis is presented and reported cases in patients
      with AIDS are reviewed. Predisposing factors include immunologic abnormalities
      (notably neutropenia), dermatitis, medications, neoplasm, and iatrogenic
      procedures, e.g., ear lavage. Treatment of malignant otitis externa has
      traditionally included anti-pseudomonal cephalosporins/penicillins and
      aminoglycosides for prolonged durations. Recently, ciprofloxacin has been shown
      to be effective as an oral regimen. With the increasing number of patients with
      AIDS being seen in the outpatient clinics, the diagnosis of malignant otitis
      externa should be considered in any patient with persistent ear pain or otorrhea
      who does not respond to conventional treatment for external otitis.

PMID- 7805600
TI  - Ear lobe keloids, surgical excision followed by radiation therapy: a 10-year
      experience.
AB  - This retrospective study was conducted to analyze the recurrence of ear lobe
      keloids in 36 patients after surgical excision followed by radiation therapy. In
      all the cases keloids were excised and the surgical wound closed primarily.
      Following surgery, patients underwent 1800 cGy of radiation therapy in three
      equally divided doses over five to seven days. Most of our patients were young
      black females who developed keloids secondary to ear lobe piercing. Of the 36
      patients followed for a mean period of 5.6 years, we noted only one (2.8%)
      recurrence. All the patients were followed for a minimum of two years. No serious
      complications were observed in our series. However, one patient developed
      radiation dermatitis followed by patchy hypopigmentation. We conclude that
      surgical excision followed by radiation therapy is a safe and effective method to
      control keloid recurrence in the ear lobe region.

PMID- 7805601
TI  - Massive epistaxis due to intracavernous carotid artery aneurysm: a case report.

PMID- 7805602
TI  - Post-operative internal valve stenosis and/or collapse.

PMID- 7805603
TI  - [Status and perspectives of the national policy on the training of human health
      resources].

PMID- 7805604
TI  - [Training the 21st-century physician and the Comprehensive Curriculum of the
      Faculty of Medicine of the Universidad Nacional Autonoma de Mexico].

PMID- 7805605
TI  - [The Mexican experience of social service in medicine. Perspectives on an ongoing
      effort].

PMID- 7805606
TI  - The Federacion Nacional de Facultades y Escuelas de Enfermeriia and the academic
      development of nursing in Mexico.

PMID- 7805607
TI  - [Characterization of dental education and the education-service connection in
      Mexico].

PMID- 7805608
TI  - [Veterinary medicine education in Mexico and its link with society].

PMID- 7805609
TI  - [Results achieved in the development of innovative projects for education in
      health fields. 20 years' experience with an innovative higher education project
      at the Universidad Autonoma Metropolitana Xochimilco].

PMID- 7805610
TI  - [Consolidating the national system for public health education].

PMID- 7805611
TI  - [The training of personnel in the processes of continuing education in the
      services].

PMID- 7805612
TI  - [Technical cooperation of the PAHO/WHO in human resources development: a new
      challenge].

PMID- 7805613
TI  - [Advanced training activities in human health resources in Mexico].

PMID- 7805614
TI  - [A selective decrease in cytochrome P450 in the liver microsomes of male rats
      following phenobarbital and 3-methylcholanthrene induction and acute
      tetrachloromethane poisoning].
AB  - The liver microsomal content of cyt. P450 and b5 and activities of selected mixed
      function oxidases were compared following phenobarbital (PB)- and 3
      methylcholantrene (MC) induction and acute intoxication with carbontetrachloride
      (CT). PB increased the content of P450 and the activities of both NADPH
      cytochrome c reductase and benzphetamin demethylase. MC increased only the
      content of cytochrome b5. CT after 4 hours damaged selectively the liver
      monoxidase components: 1. the activity of NADPH-cytochrome c reductase and the
      content of b5 were not changed in the three groups; 2. the content of P450 was
      decreased differently: more sensitive to the destructive effect of CT was the PB
      inducible P450. Most resistant was the MC-inducible P450; 3. MC decreased the
      benzphetamin demethylation in control- and PB-microsomes in lower degree than the
      content of P450. The relative high rates of the benzphetamin demethylase after CT
      by PB-microsomes was explained by increased activity of NADPH-cytochrome c
      reductase in this group. The selective damaging effect of CT on P450 was
      interpreted by complex of local factors: metabolizing of CT to CCL3, lipid
      peroxidation, phospholipid microenvironment, pO2, antioxidants concentration,
      activity of heme degrading enzymes.

PMID- 7805615
TI  - [The immunobiological functions of human ABO (H)-system blood-group antigens].
AB  - The human ABO (H) blood group antigens are genetically determined carbohydrate
      structures found in different cells and tissues. The modulation in their
      expression in the course of human onto- and oncogenesis gives grounds for
      speculations concerning the role of ABO (H) antigens as molecules, participating
      in cell interactions, adhesion and inhibition events, as well as in tumor
      metastases. The deletion of antigenic determinants observed in a number of human
      carcinomas, and the epitope homology between the blood group antigens and the
      carcinoembryonic antigen, focuses on clarifying the diagnostic and prognostic
      value of the ABO (H) antigens as tumor-associated markers.

PMID- 7805616
TI  - [The preparation of materials and the isolation of human genomic DNA for
      analysis].
AB  - The work reviews the usual and most convenient human samples (blood cells,
      fibroblasts, etc.) for extraction of DNA, storage conditions, DNA extraction
      approaches, and the criteria for assessment of quality and suitability of the
      extracted DNA for subsequent analysis. The aim of this work is to make
      professionals from different laboratory disciplines aware of the basic approaches
      to DNA sampling and storage in order to promote their further involvement in
      diagnostics and research based on DNA technology.

PMID- 7805617
TI  - [Morphological and morphometric studies of the pancreas in type-2 diabetes
      mellitus].
AB  - The authors investigated histologically and immunohistochemically 60 cases with
      diabetes mellitus type 2. By means of the morphometric method of Weibel et al.
      (1969) they established diminished volume density of the insular tissue in total
      pancreas. The morphologic and morphometric data revealed evidence that diabetes
      mellitus most probably presented a heterogeneous group of pancreatic lesions
      manifested by disturbances of carbohydrate homeostasis.

PMID- 7805618
TI  - [Morphological changes in the nervous system in lead poisoning. II. Experimental
      lead-induced encephalopathy].
AB  - The morphological investigation in an experimental model of lead (Pb)
      encephalopathy (according to the method of A. Pentschew, 1966) is presented.
      Electron microscopy-dense inclusions are found out in the nuclei and cytoplasm of
      astrocytes and in some ependyma cells in the investigated cortical and
      subcortical (paraventricular) structure of the brain and spinal cord. This
      confirms the direct toxic action of Pb on these structures and proves their
      participation in pathogeneses of the developing encephalopathy. The established
      inclusions in the ependyma and the data about a disturbance of the blood-brain
      barrier give a reason to be proposed the possibility for a penetration of Pb in
      the nervous system not only through a blood but also through a cerebrospinal
      fluid way.

PMID- 7805619
TI  - [Polypous endocarditis of the tricuspid valve. The morphological changes in the
      heart and lung in one case].
AB  - A case of polypous endocarditis which affects the tricuspid valve and whose
      genesis remains unclear (a septic state, an idiopathic disease?) is described.
      Clinically the disease has taken its course as a chronically recurring form of
      pulmonary thromboembolism. Morphologically it concerns to a massive fibroplastic
      verrucous endocarditis of the tricuspid valve and a more slightly expressed
      similar process in the wall of the right atrium and ventricle, combined with a
      significant fibrosis of the myocardium. The death has come from a massive
      thrombotic embolism in the two branches of the pulmonary artery on the background
      of a great number of small thromboembolic and hemorrhagenic infarctions with a
      different duration in the two lobes of the lung, which lead to an adaptable
      reconstruction of many lung vessels. The presence of a discrete affection of the
      aortic valve according to a rheumatic type and the combination of the disease, in
      the described case, with essential hypertension and thrombophlebitis undergone in
      the past, give a reason to discuss the possibility of taking into account these
      diseases in etiopathogenesis of the described myocardiopathy.

PMID- 7805620
TI  - [The synthesis, toxicological and comparative cytogenetic characteristics of the
      anticoagulant warfarin].
AB  - 4-hydroxy-3-(3-oxo-1-phenyl butyl)-2H-1-benzopyran-2-one (warfarin) has been
      synthesised by an original method. The influence of a phase-transfer catalyst of
      ammonium type with alkyl substituents containing eight carbon atoms upon the
      reaction of Michael addition has been investigated. It has been found out that
      when elongating the hydrocarbon chain of the substituents to the nitrogen atom in
      the quaternary ammonium salt the yield of the product decreased. The acute (LD50)
      and subchronic (lasting for 30 days) toxicity was determined when taking warfarin
      orally. The experimental data show that LD50 is 500 mg/kg for mice and 420 mg/kg
      body mass for rats. The subchronic toxicity at experiments made with rabbits
      (each day taking orally respectively 25 and 100 mg/kg) does not reveal any
      humoral and tissue toxic influence of warfarin. The results from the comparative
      cytogenetic analysis of warfarin and Niffcumar are the basis of the conclusion
      cytogenetic analysis of warfarin and Niffcumar are the basis of the conclusion
      that warfarin damages chromosomes of mice's marrow cells (used as a model) less
      than Niffcumar. Moreover warfarin has a slight influence on these cells in the
      first place changing the orientation of chromosomes one towards the other and
      unlike other drugs it does not damage nuclear chromatin strongly.

PMID- 7805621
TI  - [A pharmacological study of the hepatoprotective activity of fructose-1,6
      diphosphate].
AB  - A fructose-1,6-diphosphate preparation was tested for hepatoprotective activity
      through biochemical and morphologic studies in experiments on Wistar rats
      sustaining D-galactosamine- and paracetamole-induced hepatotoxicity. Findings
      indicated the modeled hepatic lesions to be readily reproducible, to simulate
      some characteristics of human liver pathology, and to be suitable for testing
      substances expected to have hepatoprotective action; intraperitoneal
      administration of fructose-1,6-diphosphate at a dose of 1000 mg/kg body weight
      proved moderately protective against liver damage by D-galactosamine; the benefit
      observed concerned mostly dystrophic and inflammatory changes in the liver; in a
      number of cases, correlation was noted between biochemical serum parameters and
      pathomorphologic liver alterations.

PMID- 7805622
TI  - [The determination of the biological activity of insulin by a radioreceptor
      method].
AB  - A new in vitro radioreceptor assay method for determining the biological activity
      of insulin substances is put forward. This method is designed mainly to serve the
      purposes of practice. It perfectly substitutes the biological, expensive labour
      taking and slow pharmacopoeial method. It is reproducible, does not depend on the
      season and reduces the species differences to minimum by using a mixture of
      bovine and porcine insulins (Forth International Standard) as the source of
      unlabeled insulin. The rat liver membrane receptors (preparations) retained their
      insulin-binding ability up to 10 months, when stored at -18 degrees C-(-)20
      degrees C. By means of this method the biological activity in different insulin
      preparations is established. It is found that this activity is highest in the
      monocomponent insulin substances, followed by the single-peak insulins and it's
      lowest in the conventional insulins.

PMID- 7805623
TI  - [The radioimmunological determination of porcine pancreatic polypeptide in
      Bulgarian insulin substances].
AB  - The contents of pancreatic polypeptide in insulin substances ("Pharmachim" Ltd)
      is determined in accordance to the needs of pharmaceutical production. The
      analysed insulin substances pertain to groups of different purity. The results,
      showing distribution of middle value of pancreatic polypeptide are discussed.

PMID- 7805624
TI  - [Lung metastases from tumors at different sites].
AB  - A comparative study of necropsy material is carried out for the period of 1974
      1983. For these ten years 11603 autopsies are performed. In 222 cases neoplastic
      processes with different lung metastases are obligatory, which makes 1.8% of
      total number of cases. The primary sites of these metastases are as follows:
      tumor of the stomach (26), breast (33), bile duct (10), bile ways (3), liver
      (13), large intestine (30), incretory glands (31), etc. The morphological
      evolution shows that the histologic type of the primary tumors varies
      (carcinomas, malignant lymphomas, teratocarcinomas, sarcomas, neuroblastomas,
      etc.). In some cases (carcinomas of the kidneys and liver, sarcomas of the bones)
      the histologic type of the primary tumor is identical to that of the Metastatic
      processes in the lungs. In some of the lung metastases however there are
      differences in the histological structure compared to the primary tumors. A
      clinical morphological comparative study is performed.

PMID- 7805625
TI  - KATP channels of mouse skeletal muscle: mechanism of channel blockage by AMP-PNP.
AB  - Single ATP-sensitive potassium channels (KATP channels) were studied in inside
      out membrane patches excised from mouse skeletal muscle. Channel blockage by the
      non-hydrolysable ATP analogue AMP-PNP was investigated in the absence or presence
      of 1 mM MgCl2 with K(+)-rich solutions bathing the internal membrane surface.
      Currents through single. KATP channels were recorded at -40 and +40 mV. AMP-PNP
      (5 to 500 microM; Li salt) reduced the open-probability po of KATP channels and
      decreased the single-channel currents at high nucleotide concentrations by
      approximately 10%. Half maximal reduction of po at -40 mV was observed at
      nucleotide concentrations of 29 microM in the absence and of 39 microM in the
      presence of Mg2+. The steepness of the AMP-PNP concentration-response curves was
      strongly affected by Mg2+, the Hill coefficients of the curves were 0.6 in the
      absence and 1.6 in the presence of 1 mM MgCl2. The efficacies of channel blockage
      by AMP-PNP at -40 and +40 mV were not significantly different. The results
      indicate that a KATP channel can bind more divalent Mg(2+)-complexes of AMP-PNP
      than trivalent protonated forms of the nucleotide and that channel blockage is
      hardly affected by the membrane electric field. To estimate the contribution of
      lithium ions to the observed results, we studied the effects of LiCl (0.8 to 10
      mM) in the Mg(2+)-free solution on the single channel current i. At a Li+
      concentration of 10 mM, i was hardly affected at -40 mV but reduced by a factor
      of 0.75 at +40 mV. The results are interpreted by a fast, voltage-dependent
      blockage of KATP channels by internal Li+ ions.

PMID- 7805628
TI  - Oscillations and multiple steady states in active membrane transport models.
AB  - The dynamic behavior of some non-linear extensions of the six-state alternating
      access model for active membrane transport is investigated. We use stoichio
      metric network analysis to study the stability of steady states. The bifurcation
      analysis has been done through standard numerical methods. For the usual six
      state model we have proved that there is only one steady state, which is globally
      asymptotically stable. When we added an autocatalytic step we found self
      oscillations. For the competition between a monomer cycle and a dimer cycle, with
      steps of dimer formation, we have also found self-oscillations. We have also
      studied models involving the formation of a complex with other molecules. The
      addition of two steps for formation of a complex of the monomer with another
      molecule does not alter either the number or the stability of steady states of
      the basic six-state model. The model which combines the formation of a complex
      with an autocatalytic step shows both self-oscillations and multiple steady
      states. The results lead us to conclude that oscillations could be produced by
      active membrane transport systems if the transport cycle contains a sufficiently
      large number of steps (six in the present case) and is coupled to at least one
      autocatalytic reaction,. Oscillations are also predicted when the monomer cycle
      is coupled to a dimer cycle. In fact, the autocatalytic reaction can be seen as a
      simplification of the model involving competition between monomer and dimer
      cycles, which seems to be a more realistic description of biological systems. A
      self-regulation mechanism of the pumps, related to the multiple stationary
      states, is expected only for a combined effect of autocatalysis and formation of
      complexes with other molecules. Within the six-state model this model also leads
      to oscillation.

PMID- 7805626
TI  - Fibrin structures during tissue-type plasminogen activator-mediated fibrinolysis
      studied by laser light scattering: relation to fibrin enhancement of plasminogen
      activation.
AB  - The aim was to relate fibrin structure and the stimulatory effect of fibrin on
      plasminogen activation during t-PA-mediated fibrinolysis using Lys78-plasminogen
      as activator substrate. Structural studies were undertaken by static and dynamic
      laser light scattering, cryo transmission electron microscopy and by the
      measurement of conversion of fibrin to X-, Y- and D-fragments. The kinetics of
      plasmin formation were monitored by measurement of the rate of pNA-release from
      Val-Leu-Lys-pNA. The process of fibrin formation and degradation comprised three
      phases. In the first phase, protofibrils with an average length of about 10 times
      that of fibrinogen were formed. The duration of this phase decreased with
      increasing t-PA concentration. The second phase was characterized by a sudden
      elongation and lateral aggregation of fibrin fibers, most pronounced at low
      levels of t-PA, and by formation of fragment X-polymer. The third phase was
      dominated by fragmentation of fibers and by formation of Y- and D-fragments.
      Plasmin degraded the fibers from within, resulting in the formation of long loose
      bundles, which subsequently disintegrated into thin filaments with a length of
      less than 10 and a mass per length close to one relative to fibrinogen. Plasmin
      generation at high t-PA concentrations sets in just prior to (and at low t-PA
      concentrations shortly after) the onset of the rapid second phase of elongation
      and lateral aggregation of fibrin fibers. The maximal rate of plasmin formation
      per mol t-PA was the same at all concentrations of activator and was achieved
      close to the time of the peak level of fragment X-polymer. Plasmin formation
      ceased after formation of substantial amounts of Y- and D-fragments. At this
      stage the length was between 300 and 3 and the mass per length close to 1, both
      relative to fibrinogen. In conclusion our results indicate that (1) formation of
      short fibrin protofibrils is the minimal requirement for the onset of the
      stimulatory effect of fibrin on plasminogen activation by t-PA, (2) formation of
      fragment X protofibrils is sufficient to induce optimal stimulation of
      plasminogen activation, and (3) plasmin degrades laterally aggregated fibrin
      fibers from within, resulting in the conversion of the fibers into long loose
      bundles, which later disintegrate into thin filaments.

PMID- 7805627
TI  - Contributions of tryptophan side chains to the far-ultraviolet circular dichroism
      of proteins.
AB  - It has often been assumed that the role of aromatic side chains in the far
      ultraviolet region of protein circular dichroism (CD) is negligible. However,
      some proteins have positive CD bands in the 220-230 nm region which are almost
      certainly due to aromatic side chains. The contributions to the CD of
      interactions between tryptophan side chains and the nearest neighbor peptide
      groups have been studied, focusing on the indole Bb transition which occurs near
      220 nm. Calculations on idealized peptide conformations show that the CD depends
      strongly on both backbone and side-chain conformation. Because of the low
      symmetry of indole, rotation about the C beta C gamma bond (dihedral angle chi 2)
      by 180 degrees generally leads to large changes in the CD, often causing the Bb
      band to reverse sign. When side-chain conformational preferences are taken into
      account, there is no strong bias for either positive or negative Bb rotational
      strengths. The observation that simple tryptophan derivatives such as N-acetyl-L
      tryptophan methylamide have positive CD near 220 nm implies either that these
      derivatives prefer the alpha R region over the beta region, or that there is
      little preference for chi 2 < 180 degrees over chi 2 > 180 degrees. Nearest
      neighbor-only calculations on individual tryptophans in 15 globular proteins also
      reveal a small bias toward positive Bb bands. Rotational strengths of the Bb
      transition for some conformations can be as large as approximately 1.0 Debye-Bohr
      magnetons in magnitude, corresponding to maximum molar ellipticities greater than
      10(5) deg cm2/dmol. Although a substantial amount of cancellation occurs in most
      of the examples considered here, such CD contributions could be significant,
      especially in proteins of low helix content.

PMID- 7805629
TI  - Compactness of protein molten globules: temperature-induced structural changes of
      the apomyoglobin folding intermediate.
AB  - Apomyoglobin undergoes a two-step unfolding transition when the pH is lowered
      from 6 to 2. The partly folded intermediate (I) state at pH 4 and low ionic
      strength has properties of a molten globule. We have studied structural features
      of this state, its compactness, content of secondary structure, and specific
      packing of aromatic side chains, using dynamic light scattering, and small-angle
      X-ray scattering and far- and near-ultraviolet circular dichroism spectroscopy.
      Particular attention was paid to temperature-dependent structural changes. The
      results are discussed with reference to the native-like (N) state and the highly
      unfolded (U) state. It turned out that the I-state is most compact near 30
      degrees C, having a Stokes radius 20% larger and a radius of gyration 30% larger
      than those of the N-state. Both cooling and heating relative to 30 degrees C led
      to an expansion of the molecule, but the structural changes at low and high
      temperatures were of a different kind. At temperatures above 40 degrees C non co
      operative melting of structural elements was observed, while the secondary
      structure was essentially retained on cooling. The results are discussed in
      context with theoretical predictions of the compactness and the stability of
      apomyoglobin by Alonso et al. [Alonso, D. O. V., Dill, K. A., and Stigter, D.
      (1991) Biopolymers 31:1631-1649]. Comparing the I-state of apomyoglobin with the
      molten globules of alpha-lactalbumin and cytochrome c, we found that the
      compactness of the molten globule states of the three proteins decreases in the
      order alpha-lactalbumin > apocytochrome c > apomyoglobin.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7805630
TI  - Behavioral treatment of childhood obesity: theoretical and practical
      implications.
AB  - The impressive 10-year success of behavioral treatment of childhood obesity
      stands in marked contrast to the disappointing long-term results obtained with
      obese adults. It may be easier to teach children healthy eating and activity
      habits. Parents also regulate access to food, thereby reducing the importance of
      self-control. Whether treatment of childhood obesity affects the later
      development of an eating disorder is a question that calls for future research.

PMID- 7805631
TI  - Ten-year outcomes of behavioral family-based treatment for childhood obesity.
AB  - We report 10-year treatment outcomes for obese children in 4 randomized treatment
      studies. At 10 years, 34% decreased percentage overweight by 20% or more, and 30%
      were not obese. Significant effects were observed when parents and children were
      targeted and reinforced for weight loss in comparison with nontargeted controls
      and for children given lifestyle or aerobic exercise in comparison with a
      calisthenics control. Thirty-four percent of the variance in change in percentage
      overweight was predicted from sex, baseline percentage overweight, self
      monitoring weight, meals eaten at home, and family and friends' support for
      eating and exercise. Results show long-term changes in children depend on the
      treatment, and evidence converges on the importance of the family and other
      sources of support for eating and activity change.

PMID- 7805632
TI  - Gender in medical encounters: an analysis of physician and patient communication
      in a primary care setting.
AB  - The relation of physician and patient gender to verbal and nonverbal
      communication was examined in 100 routine medical visits. Female physicians
      conducted longer visits, made more positive statements, made more partnership
      statements, asked more questions, made more back-channel responses, and smiled
      and nodded more. Patients made more partnership statements and gave more medical
      information to female physicians. The combinations of female physician-female
      patient and female physician-male patient received special attention in planned
      contrasts. These combinations showed distinctive patterns of physician and
      patient behavior, especially in nonverbal communication. We discuss the relation
      of the results to gender differences in nonclinical settings, role strains in
      medical visits, and current trends in medical education.

PMID- 7805633
TI  - Readiness to quit as a predictor of smoking changes in the Minnesota Heart Health
      Program.
AB  - The relation between two indexes of readiness to quit smoking obtained at
      baseline and subsequent quitting 2-7 years later was examined. Baseline data from
      the Minnesota Heart Health Program were used to construct 3-item composites of
      interest in quitting (alpha = .76) and past quitting behavior (alpha = .64). With
      baseline smoking controlled, both measures predicted quitting at the 2- and 7
      year follow-ups but not at 4 years. Only interest in quitting was significant at
      the 7-year follow-up when both indexes entered the model. Given the
      representative community sample and the long interval from baseline to the final
      assessment, the findings provide support for the readiness construct.

PMID- 7805634
TI  - Reducing inner-city women's AIDS risk activities: a study of single, pregnant
      women.
AB  - Behavioral change reduces risk of HIV infection and development of AIDS. We
      compared 206 inner-city women who were randomly assigned to a 4-session AIDS
      prevention group or to one of two controls, a health-promotion group or a no
      intervention group. AIDS-prevention and health-promotion groups provided
      information, behavioral competency training, and social support. Only the AIDS
      prevention group focused on AIDS-specific knowledge and skills. The AIDS
      prevention group produced moderate, consistent increases in knowledge and safer
      sex behaviors in comparison with either the health-promotion or no-intervention
      group. Self-report and objective changes were sustained 6 months after
      intervention for both African-American and European-American women.

PMID- 7805635
TI  - Comparison of three theories relating facial expressiveness to blood pressure in
      male and female undergraduates.
AB  - We examined differing predictions of how emotional expressions and blood pressure
      are related. Spontaneous positive and negative facial expressions, resting
      systolic blood pressure (SBP), and reactive SBP were each measured for 148 male
      and female undergraduates. The discharge theory of emotions proposes that few
      expressions will predict higher baseline SBP, and this was found for men. A
      mismatch theory of emotions proposes that an imbalance between positive and
      negative expressions will predict higher baseline SBP, and this was supported for
      women. Finally, coactivation theory proposes that many expressions will predict
      higher reactive SBP, and this was found for both men and women. These results
      reconcile previous conflicting findings by clarifying the conditions under which
      each of these theories may be supported.

PMID- 7805636
TI  - Predictors of Norwegian adolescents' sunbathing and use of sunscreen.
AB  - A nationwide random sample of 15,169 Norwegian high school students completed a
      questionnaire about tanning habits, physical self-concept, attitudes, beliefs,
      and values. Although 90% of the adolescents did use sunscreen, less than 25% used
      an adequate sun-protection factor, and only 50% applied the sunscreen an adequate
      number of times when sunbathing. Multiple regression analyses identified these
      predictors of sunbathing: opportunity to sunbathe, tender skin, heavy smoking,
      playing down the risk for skin cancer, valuing physical appearance, friends' use
      of sunscreen (girls only), a positive attitude toward having a tan, favorable
      physical self-concept, friends' use of sunbeds, and friends' sunbathing.
      Sunscreen use was also predicted by opportunity to sunbathe and skin type.
      Furthermore, the effects of perceived risk for skin cancer and peers' use of
      sunscreen were particularly strong.

PMID- 7805637
TI  - Predictors of attrition in health intervention research among older subjects with
      osteoarthritis.
AB  - Attrition in an experimental osteoarthritis intervention was studied among 364
      (130 male) volunteers (ages 60-87). Subjects were randomly assigned to control,
      social support, education, or combined treatment groups. A series of discriminant
      function analyses showed that the final intervention groups were more homogeneous
      than the original samples. The most robust predictor of attrition was having
      either high or very low depression scores. Social support variables were
      predictors of poor attendance in the social support group, indicating possible
      attrition bias in evaluating this treatment. The results indicate that
      psychosocial variables may be the best predictors of attrition in health
      intervention research among older subjects, and that variables related to
      attrition can be related to the content of the intervention.

PMID- 7805638
TI  - Specificity in social support: perceptions of helpful and unhelpful provider
      behaviors among irritable bowel syndrome, headache, and cancer patients.
AB  - Perceived social support was assessed among 53 patients suffering from non-life
      threatening chronic illnesses (i.e., irritable bowel syndrome or recurrent
      headache). Subjects recalled predominantly helpful support interactions and
      reported the three major types of social support as equally helpful. In addition,
      irritable bowel syndrome patients, who experience embarrassing physical symptoms,
      reported fewer instances of tangible assistance than chronic headache patients.
      Comparisons to cancer patients studied by Dakof and Taylor (1990) revealed
      differences in perceived social support as a function of diagnosis. These results
      offer insight into the needs of patients with noncatastrophic illnesses and
      suggest that the challenges and tasks confronting these individuals are unique
      from those encountered by patients with catastrophic diseases.

PMID- 7805639
TI  - Daily events are associated with a secretory immune response to an oral antigen
      in men.
AB  - To examine a hypothesized link between daily stressful events and secretory
      immunoglobulin A (sIgA) antibody, 96 adults from the community completed daily
      event questionnaires and gave daily saliva samples for up to 12 weeks. They also
      ingested a capsule of a novel protein to challenge their secretory immune
      systems. The questionnaire yielded measures of negative and positive experiences,
      of their content, and of negative and positive affect. On a within-subjects, day
      to-day basis, reporting more desirable events was related to more sIgA antibody,
      and reporting more undesirable events was related to less. Desirable events also
      had lagged (1 and 2 days), positive effects on sIgA levels. Undesirable work
      events and desirable leisure and household events were more strongly related to
      sIgA than events in other categories. Positive affect related directly to sIgA,
      and negative mood related inversely to same-day sIgA.

PMID- 7805641
TI  - Anticonvulsant effects of the experimental induction of hippocampal theta
      activity.
AB  - Epileptic seizures occur less during wakefulness or paradoxical sleep, conditions
      during which hippocampal theta rhythm is seen. This leads to the hypothesis that
      this rhythm indicates a physiological state of the hippocampal formation which
      opposes its recruitment into seizures. This was tested by determining the effects
      of experimental induction or suppression of hippocampal theta activity on
      seizures. Hippocampal theta activity can be induced by chemical or electrical
      stimulation of the medial septal nucleus and adjacent nucleus of the diagonal
      band of Broca. Microinjections of the muscarinic agonist carbachol in the medial
      septum during pentylenetetrazol (PTZ) induced facial-forelimb seizures stopped
      behavioral seizures and EEG spiking within five seconds, and caused hippocampal
      theta activity. Medial septal electrical stimulation at 4-8 Hz had similar
      effects. Electrolytic medial septal lesions abolished hippocampal theta activity
      and lowered myoclonic and facial-forelimb PTZ seizure thresholds. Medial septal
      carbachol injections were also made during electrically kindled limbic status
      epilepticus. Within ten seconds, ictal behavior stopped and the EEG spike rate
      decreased by half with a gradual return to the baseline rate over three minutes.
      These results demonstrate that the hippocampal theta rhythm corresponds to a
      seizure-resistant condition, providing a possible explanation for the seizure
      promoting properties of slow wave sleep.

PMID- 7805640
TI  - Differential expression of the astrocytic enzymes 3-hydroxyanthranilic acid
      oxygenase, kynurenine aminotransferase and glutamine synthetase in seizure-prone
      and non-epileptic mice.
AB  - Previous investigations in seizure-prone mice have suggested that an abnormally
      elevated production of the astrocyte-derived neuroexcitant, quinolinic acid
      (QUIN), plays a role in seizure susceptibility. In order to evaluate further the
      role of QUIN metabolism in genetic murine seizure models, the activities of its
      biosynthetic enzyme 3-hydroxyanthranilic acid oxygenase (3HAO), and of two other
      astrocytic enzymes, kynurenine aminotransferase (KAT) and glutamine synthetase
      (GS), were measured in the brains of seizure-prone EL and DBA/2 mice and two non
      epileptic strains (BALB/c and Swiss-Webster). 3HAO activity was found to be
      markedly higher in both EL and DBA/2 mice than in the non-epileptic strains in
      all brain regions examined. The activity of 3HAO was not modified by the tossing
      procedure employed to promote seizures in EL mice. While some strain differences
      were noted in the activities of KAT and GS, these enzymes did not distinguish
      seizure-prone from the non-epileptic mice. In order to delineate better the
      relationship between glial activation and 3HAO, KAT and GS, further studies were
      performed in the ibotenate-lesioned hippocampus. In mice (but not in rats), the
      activity of 3HAO was selectively increased in gliotic tissue. These data
      demonstrate substantial species and strain differences in astroglial enzymes and
      in their response to brain injury. The observation of widespread abnormally high
      3HAO activity in two distinct seizure-prone mouse strains strengthens the
      hypothesis that enhanced production of QUIN contributes to seizure susceptibility
      in mice.

PMID- 7805642
TI  - Hippocampal CA1 neuronal properties in genetically epilepsy-prone rats: evidence
      for increased excitation.
AB  - The genetically epilepsy prone rats (GEPRs) are abnormally susceptible to
      seizures with a variety of treatments and can be used as a model to study
      generalized seizure predisposition involving the brainstem and forebrain
      structures. We investigated the basic membrane and synaptic properties of
      hippocampal CA1 cells in Sprague-Dawley (SD) rats and GEPRs. Several differences
      in cellular properties were observed in the GEPRs. These include an increase in
      membrane input resistance and reduced spike frequency adaptation in the majority
      of GEPR cells. A decrease in the amount of current required to elicit a 5-mV EPSP
      was observed in the GEPR. A marked increase in excitability with paired pulse
      stimulation was also observed in GEPRs both in extracellular population spikes
      and intracellular EPSPs. Applying bicuculline, a GABAA antagonist, markedly
      increased paired pulse facilitation of the population spike in SD rats but in
      GEPRs produced only a minimal effect on facilitation. This difference suggests
      reduced GABAA-mediated inhibition in GEPR hippocampus with paired pulse
      stimulation. Several factors could interact or act independently to produce these
      effects because the epileptic phenotype in GEPRs is regulated by multiple genes.

PMID- 7805643
TI  - The effect of thyrotropin-releasing hormone (TRH) on limbic status epilepticus in
      rats.
AB  - We produced limbic status epilepticus in rats by injecting a combination of
      dibutyryl-cAMP (db-cAMP) and ethylenediaminetetraacetic acid (EDTA) into the
      amygdala (AM). Thirty minutes after intra-AM db-cAMP/EDTA injection, thyrotropin
      releasing hormone (TRH) was administered intravenously or
      intracerebroventricularly. Intravenous TRH (3, 25, 50 mg/kg) produced immediate
      activation of electroclinical seizures, lasting for 25-45 min. In some animals
      which showed this seizure activation, complete seizure suppression occurred 55-70
      min after the TRH treatment. Similar activation of ictal seizures with delayed
      seizure suppression was obtained after intracerebroventricular TRH (25, 50
      micrograms). The findings suggest that the effects of intravenous TRH are due to
      its central action and that the use of intravenous TRH is not a promising
      approach for the treatment of status epilepticus.

PMID- 7805644
TI  - Phenytoin concentrations in the human brain: an in vivo microdialysis study.
AB  - We report the first human study of phenytoin concentration using in vivo
      microdialysis, which permits sampling the extracellular environment of the brain.
      This technique has been applied to patients undergoing intracranial electrode
      investigation for intractable epilepsy. By varying the rate of perfusion (from
      2.5 to 0.25 microliters/min), it is possible to quantify the concentration of
      drug in the extracellular fluid (ECF), which reflects the concentration on the
      outer neuronal cell membrane. Samples were obtained from four catheters in two
      patients, in whom serum phenytoin (PHT) concentrations were held constant.
      Unbound serum concentrations were measured following ultrafiltration at 37
      degrees C. In one patient, with left and right hippocampal probes, steady state
      ECF/unbound serum ratios were 87 and 84% respectively. In the second patient,
      with hippocampal and frontal probes, ECF/unbound serum ratios were 87 and 85%
      respectively. Flow rate for 50% maximal recovery averaged 1.65 microliters/min
      (1.5-1.7 microliters/min). We found that steady state ECF PHT concentrations
      corresponded closely to unbound serum concentrations. No differences are observed
      between different sites within the brain. Flow rates needed for equilibration of
      dialysate with the extracellular space were slower than reported for
      carbamazepine, but faster than those we found for carbamazepine-epoxide and
      valproate.

PMID- 7805645
TI  - Dendritic morphology in epileptogenic cortex from TRPE patients, revealed by
      intracellular Lucifer Yellow microinjection and confocal laser scanning
      microscopy.
AB  - Biopsy material was obtained from cortical epileptogenic zones (eight temporal,
      one occipital, one parietal and one frontal) of eleven patients aged 1.5-47 years
      with therapy-resistant partial epilepsy (TRPE) undergoing epilepsy surgery.
      Control autopsy material (two temporal, two occipital, one parietal and one
      frontal) was removed from six neurologically healthy cases within 6-10 hours
      postmortem delay. In each specimen, 100-300 pyramidal and non-pyramidal neurons
      were visualized by intracellular Lucifer Yellow microinjection. Single neurons
      were imaged using CLSM generated serial optical sections; 2-D reconstruction of
      each neuron was made using z-projection of serial optical images, and 3-D
      reconstructions and rotations were computerized. Neuronal maps from TRPE
      biopsies, compared to control autopsies, show markedly increased numbers of
      dendritic abnormalities of single pyramidal and non-pyramidal neurons in layers
      I, II-III, V-VII, and in the subcortical white matter. The abnormalities include:
      (1) increased number of non-pyramidal cells in layer I; (2) many pyramidal cells
      with two or three dendrites originating apically, rather than one single apical
      dendrite, in layers II-III; (3) atypical orientation of oblique apical and basal
      dendrites in pyramidal neurons of layers II-VII; (4) increased number of atypical
      'dinosaur-like' and fusiform cells in layers V-VII; (5) numerous neurons in the
      white matter. These abnormalities may be etiological in cases with early onset,
      and predisposing in cases with late onset.

PMID- 7805646
TI  - The cost of epilepsy in the United Kingdom: an estimation based on the results of
      two population-based studies.
AB  - Epilepsy has important socio-economic costs to a population. It is important to
      assess these costs so that health care priorities can be set. We assessed the
      burden of illness of epilepsy at the community level, and from this we were able
      to estimate costs for an individual and the cost to the United Kingdom (UK) as a
      whole. Cost analysis was based on two different populations of patients with
      epilepsy, a prevalent and an incident population. Patients with established
      epilepsy (n = 1628), who were identified from general practices throughout the UK
      as part of the National Epilepsy Survey (NES), and patients with newly diagnosed
      epilepsy (n = 602), from the National General Practice Study of Epilepsy (NGPSE),
      which is a prospective longitudinal cohort study of epilepsy. Indirect and direct
      costs were assessed in the NES, and direct costs in the NGPSE. A longitudinal
      cost profile of epilepsy was calculated, with an average initial direct costs of
      611 pounds (US$917) per patient per annum which decreased after eight years of
      follow up to 169 pounds (US$254) per patient per annum. The cost to the UK of
      newly diagnosed epilepsy in the first year of diagnosis was 18 million pounds
      (US$27 million). The total annual cost of established epilepsy to the UK was
      estimated at 1930 million pounds (US$2895 million), over 69% of which was due to
      indirect costs (unemployment and excess mortality). The cost of active epilepsy
      per patient was approximately 4167 pounds (US$6251), and of inactive epilepsy
      1630 pounds (US$2445) per patient per annum. Methodological issues in cost
      studies of epilepsy are reviewed.

PMID- 7805647
TI  - Factors influencing the risk of abnormal pregnancy outcome in epileptic women: a
      multi-centre prospective study.
AB  - We studied pregnancy outcome in preconceptionally recruited epileptic and control
      women in a multi-centre prospective non-intervention study at two university
      hospitals and three general hospitals. We evaluated 225 singleton pregnancies:
      119 pregnancies of epileptic women who received either antiepileptic drugs (AEDs)
      (n = 99) or not (n = 20), and 106 pregnancies of controls. The main outcome
      measures were abnormal pregnancy outcome: major and minor congenital
      malformations, ectopic pregnancies, abortions; neonatal headcircumference; birth
      weight and birth length. Epileptic women had a two-fold risk of having an
      abnormal pregnancy outcome or an infant with minor malformations compared to
      healthy controls (odds ratio, with 95% confidence interval, respectively 2.1
      (1.1, 4.0) and 2.0 (1.0, 4.0)). A significant correlation between the prevalence
      of abnormal pregnancy outcome and duration of epilepsy and AED treatment was
      found (risk increased by 9% (6%, 16%) per annum). No significant effect in terms
      of the type, the number or the serum level of the AEDs could be established. The
      head circumference of infants of epileptic mothers was significantly smaller (0.7
      (1.2, 0.28 cm) compared to controls. An effect on the outcome of pregnancy of
      maternal folate supplementation or of folate blood concentrations during the
      periconceptional period and first trimester of pregnancy could not be determined.
      The severity of maternal epilepsy and/or AED treatment influences pregnancy
      outcome.

PMID- 7805648
TI  - Physiology of the hypothalamic-pituitary-adrenal axis in health and dysregulation
      in psychiatric and autoimmune disorders.
AB  - The HPA axis is the principal effector of the generalized stress response and
      crucial for maintaining basal and stress-related homeostasis. There has been an
      exponential increase in knowledge regarding the interactions among the elements
      of the HPA axis (CRH, AVP, ACTH, glucocorticoids) and between the HPA axis and
      the other components of the stress system (locus ceruleus/norepinephrine
      sympathetic systems), as well as with the axes responsible for reproduction,
      growth, and immunity. This new knowledge has allowed association of HPA axis
      dysfunction, characterized by sustained hyperactivity or hypoactivity, to various
      pathophysiologic states that cut across the traditional boundaries of medical
      disciplines. These include a range of psychiatric, endocrine, and inflammatory
      disorders or susceptibility to such disorders.

PMID- 7805649
TI  - Proopiomelanocortin-derived peptides.
AB  - Cloning of the cDNA of POMC mRNA led to the characterization of the ACTH
      precursor and established the molecular links between ACTH, beta LPH and gamma
      LPH, and beta end. Further previously unidentified POMC-derived peptides were
      also unravelled, including the N-terminal fragment and the JP. POMC is a
      precursor polypeptide that contains the amino acid sequences of numerous small
      polypeptide products. It contains eight pairs of basic amino acids and one
      sequence of four basic amino acids, which are the sites of cleavage for the
      recently identified prohormone convertases (PC1 and PC2), which have different
      specificities. PC1 but not PC2 is found in corticotroph cells of the anterior
      pituitary and cleaves POMC to generate NT, JP, ACTH, beta LPH and small amounts
      of gamma LPH and beta end. In the melanotroph cells of the intermediate
      pituitary, both PC1 and PC2 are present. The proteolysis of POMC is thus more
      extensive, resulting in a series of smaller peptides including gamma MSHs, CLIP,
      alpha MSH, beta MSH, beta end, and beta end. Equimolar amounts (because they are
      all products of the same precursor) of the POMC peptides are released into the
      blood by exocytosis from corticotroph cells of the anterior pituitary. No
      physiological role has been definitively identified for any of these products
      other than ACTH. POMC peptides have been assayed in human blood by specific
      radioimmunoassay (RIA). In most circumstances, the concentrations of all these
      peptides are perfectly correlated. Therefore, for practical reasons, LPH RIA is
      widely used as an indicator of overall corticotroph function. In rare cases, the
      correlation between the POMC peptides is disrupted by a general disorder
      selectively modifying the metabolism of the different members of the family as in
      chronic renal failure, or in tumors where POMC processing is abnormal. Examples
      include pituitary macroadenomas, some silent corticotroph adenomas, and most
      frequently non-pituitary tumors responsible for ectopic ACTH syndrome. These
      pathologies can lead to the formation and secretion into blood of CLIP and beta
      MSH, or alternatively POMC may be underprocessed and secreted intact. An elegant
      approach, specific IRMA, has been developed to directly recognize unprocessed
      POMC in blood.

PMID- 7805650
TI  - Glucocorticoid action and the clinical features of Cushing's syndrome.
AB  - Glucocorticoids mainly act through binding to cytosolic receptors that
      translocate to the nucleus after ligand binding, and dimerize to affect gene
      transcription in multiple fashions. The liganded receptors may interact with DNA
      at specific glucocorticoid responsive-elements, may physically hinder the ability
      of other transcription-regulating proteins to interact with their own DNA
      response-elements, and may form intranuclear complexes with the transcription
      factor c-jun, thus changing the number of c-jun/c-fos heterodimers that bind at
      AP-1 sites. By these, and perhaps other, mechanisms, physiologic concentrations
      of glucocorticoids regulate normal tissue metabolism, and supraphysiologic
      concentrations cause Cushing's syndrome. Cushing's syndrome leaves virtually no
      body tissue untouched. Left untreated, it results in progressive adiposity,
      myopathy, dermopathy (atrophy, stria, purpura, and hirsutism), psychopathy,
      glucose intolerance, hypercholesterolemia, hypertension, atherosclerosis,
      immunosuppression, and, ultimately, death. The physiology underlying each of
      these effects of hypercortisolism has been reviewed. The differences in the
      presentation of Cushing's syndrome in children and adults have also been
      discussed. The goal of the clinician must be to identify individuals with
      Cushing's syndrome as early in the course of the disease as possible so as to
      avoid the devastating complications that result from prolonged hypercortisolism.
      In patients for whom screening tests are equivocal, or only intermittently
      elevated, it may be necessary to re-evaluate the patient over time to establish
      that the patient has hypercortisolism. Some clinical guidelines for which
      patients to screen for hypercortisolism have been presented. Once
      hypercortisolism is established, patients with mild hypercortisolism (urine free
      cortisol less than four-fold above the upper limit of normal) should undergo
      tests to differentiate true Cushing's syndrome from a pseudo-Cushing state.

PMID- 7805651
TI  - Biochemical and radiologic diagnosis of Cushing's syndrome.
AB  - In summary, the technological advances in the past decade have greatly improved
      the biochemical and radiological diagnosis of Cushing's syndrome. Figure 13
      illustrates an algorithm for the differential diagnosis of Cushing's syndrome
      that focuses on the importance of ACTH-IRMA and provides two potential diagnostic
      approaches for the evaluation of ACTH-dependent hypercortisolism. The first
      approach directly proceeds to IPSS as the most rapid and possibly most cost
      effective method to establish an accurate diagnosis. A more traditional approach
      employs high dose dexamethasone suppression testing followed by MR studies of the
      pituitary. If the biochemical or radiological studies are the least bit
      equivocal, IPSS should be performed before definitive therapy is recommended.

PMID- 7805652
TI  - Epidemiology of Cushing's syndrome and subclinical disease.
AB  - Adenomatous lesions of the adrenal are commonplace. Advances in imaging
      technology have resulted in the discovery of increasing numbers of these lesions.
      A variety of hormonal and anatomic evaluations have been suggested to distinguish
      between the benign and potentially harmful of these lesions. Among the suggested
      evaluations is assessment of the feedback regulation of cortisol secretion.
      Several studies have confirmed that approximately 10% of the adenomas secrete
      cortisol in at least a partially unregulated manner. These patients, defined as
      having either subclinical or preclinical Cushing's syndrome, frequently undergo
      extensive diagnostic testing and on occasion, adrenalectomy. The relative
      infrequency of Cushing's syndrome in the general population suggests strongly
      that the vast majority of individuals identified by subjecting all patients with
      incidentally discovered adrenal masses to screening tests for excess cortisol
      secretion will never progress to clinically significant disease (clinical
      Cushing's syndrome). Thus, testing of this nature in the absence of clinical
      findings consistent with Cushing's syndrome is counterproductive and should
      generally not be performed. Individuals with these masses should, however,
      receive close clinical follow-up and testing initiated if any findings suggestive
      of Cushing's syndrome develop. The application of screening tests in a relatively
      unselected population is clinically ineffective and can be deleterious when
      patients without disease undergo subsequent invasive procedures. The clinical
      epidemiology af adrenal Cushing's syndrome, the natural history of incidentally
      discovered adrenal lesions, and the lack of clearly documented benefits in
      removing lesions from patients with subclinical disease argue strongly against
      use of a biochemical screen ion the decision to operate.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7805653
TI  - Pathogenesis of pituitary Cushing's syndrome. Pituitary versus hypothalamic.
AB  - There has been a long-standing controversy as to whether Cushing's syndrome is
      primarily a hypothalamic disorder, with the pituitary simply responding to excess
      of CRH or other factors, or whether the defect lies at the level of the
      pituitary. Current data suggest that in nearly all cases, the tumor is clonal,
      implying a genetic defect at the level of the pituitary. The specific
      abnormalities underlying the development of corticotroph adenomas remain to be
      determined. It is certainly possible that the historical controversy has created
      an artificial dichotomy in our thinking about the pathogenesis of Cushing's
      syndrome and that hypothalamic factors may play a permissive role in the clonal
      expansion of a mutated pituitary cell. Finally, the finding of polyclonality in
      hyperplastic corticotroph tissue from a patient with an ectopic CRH-secreting
      tumor suggests there may be a more direct role for CRH in the pathogenesis of
      Cushing's syndrome in rare cases.

PMID- 7805654
TI  - Cushing's syndrome and the nodular adrenal gland.
AB  - This article examines Cushing's syndrome in four main categories as associated
      with nodular adrenal glands: adrenal adenoma, adrenal carcinoma, primary
      pigmented nodular adrenal dysplasia, and macronodular adrenal hyperplasia. A
      summary of clinical features of these four categories is presented.

PMID- 7805655
TI  - Cushing's syndrome. Therapy directed at the adrenal glands.
AB  - Establishing the exact etiologic diagnosis of Cushing's syndrome is fundamental
      to the management of the disease. It allows for specific therapy, such as
      pituitary microsurgery. In cases where the adrenal gland is the cause, treatment
      can be either surgical or medical. This article explores both types of treatment
      and their respective results.

PMID- 7805656
TI  - Ectopic ACTH syndrome and CRH-mediated Cushing's syndrome.
AB  - The ectopic ACTH syndrome accounts for a substantial number of patients with
      naturally occurring Cushing's syndrome. Despite the progress achieved in
      elucidating the pathophysiology of Cushing's syndrome, clinicians continue to
      experience diagnostic and therapeutic challenges. This is especially true in
      those patients presenting with disease mediated by ectopically produced ACTH and
      CRH. Patients with these disorders may be indistinguishable based on clinical
      grounds or simple biochemical and radiologic testing from those with Cushing's
      disease. However, this differentiation is critical because their therapies
      differ. While clinical researchers continue to develop more effective diagnostic
      techniques and therapies, further advances in the molecular and cell biology of
      ACTH and CRH-producing tumors will undoubtedly shed light on the pathogenesis of
      this perplexing, fascinating and still controversial entity.

PMID- 7805657
TI  - Cushing's syndrome from the patient's perspective.
AB  - Forty-one patients with Cushing's syndrome described the physical, mental, and
      emotional effects of the disease, and the effects that the disease has on their
      families and performance at work or school. The majority of patients reported
      that Cushing's syndrome greatly affected everyday life. Areas in which physicians
      and nurses can provide critical assistance and support are described.

PMID- 7805658
TI  - Cushing's syndrome and pregnancy.
AB  - Women with active Cushing's syndrome rarely conceive. Only about 69 pregnancies
      have been reported in women with Cushing's syndrome, 60 of whom had maternal and
      fetal complications. Fourteen of the women have had therapy with unilateral
      adrenalectomy, bilateral adrenalectomy, pituitary surgery with selective
      adrenomectomy, or pituitary radiation.

PMID- 7805659
TI  - Cushing's disease in children.
AB  - As with adults, the diagnosis of Cushing's disease in childhood can be difficult.
      The clinical presentation in children is distinctive in terms of the effects on
      growth and pubertal development. The biochemical diagnosis can usually be made
      with standard dexamethasone suppression testing, similar to such testing in
      adults. The clinical course of Cushing's disease in children tends to be more
      aggressive than in adults, as evidenced by higher rates of Nelson's syndrome
      after bilateral adrenalectomy and higher rates of recurrence after removal of
      corticotrope adenomas. TSS is well tolerated in children and has fewer side
      effects than other modalities. Currently, pituitary irradiation is best reserved
      as adjunctive therapy. Newer stereotactic computer assisted linear accelerator
      techniques (e.g., proton knife) may provide increased effectiveness with fewer
      side effects and be particularly useful in childhood Cushing's disease.
      Appropriate treatment of children with Cushing's disease can be compatible with
      satisfactory psychosocial adjustment and fertility in adulthood.

PMID- 7805660
TI  - Glucocorticoids and osteoporosis.
AB  - In summary, patients who will remain on glucocorticoids for more than a few weeks
      are clearly at risk for osteoporosis. A list of therapeutic strategies is
      provided in Table 2. While our therapy remains inadequate at this time, newer
      agents are on the horizon. In the near future, it may be possible to recommend
      specific agents for prevention of osteoporosis. Until longer term studies are
      completed, careful attention to the method of glucocorticoid administration,
      maintenance of exercise, supplementation with Vitamin D if needed, and adequate
      calcium intake are the mainstays of prevention. Possible treatments in the near
      future may include newer bisphosphonates, growth factors, and newer forms of
      calcitonin.

PMID- 7805661
TI  - Glucocorticoids and infection.
AB  - Glucocorticoids alter the host response to both common and unusual infectious
      agents through widespread effects on immunity and the inflammatory process.
      Patients with ectopic ACTH syndrome or with exposure to high doses of exogenous
      glucocorticoids are at highest risk of infection. Care of these patients involves
      decreasing the levels of glucocorticoids whenever possible, preventing exposure
      to infectious agents, and aggressively evaluating patients with suspected
      infection.

PMID- 7805662
TI  - Comparative aspects of Cushing's syndrome in dogs and cats.
AB  - Naturally occurring hyperadrenocorticism (Cushing's syndrome) is extremely common
      in dogs, with an incidence far greater than that in humans. The incidence of the
      syndrome in cats, much less frequently diagnosed than in dogs, probably is
      similar to that in humans. Many features of canine hyperadrenocorticism are
      strikingly similar to those in humans; however, several alterations in dogs are
      unique and not observed in other species. Clinical features and hospital testing
      abnormalities are reviewed in this article.

PMID- 7805663
TI  - Fatigue and recovery of phosphorus metabolites and pH during stimulation of rat
      skeletal muscle: an evoked electromyography and in vivo 31P-nuclear magnetic
      resonance spectroscopy study.
AB  - 31P-nuclear magnetic resonance spectroscopy and evoked electromyography were
      applied to rat skeletal muscle to examine the mechanism of muscle fatigue and the
      recovery of muscle phosphorus metabolites and pH during fatigue. When the sciatic
      nerve was electrically stimulated at 1 Hz, the contraction force of the
      gastrocnemius muscle decreased gradually to 46% of the maximal force, accompanied
      by a decrease in phosphocreatine (PCr) and a corresponding increase in inorganic
      phosphate (P(i)) and diprotonated inorganic phosphate (H2PO4-). Neither the
      amplitudes of compound muscle action potentials (CMAP) nor muscle pH changed
      significantly. At 10-Hz stimulation, contraction force rapidly decreased to 26%
      of maximal force, accompanied by a decrease in PCr and increases in P(i) and
      H2PO4-. Muscle pH decreased for a few minutes, then gradually recovered during
      continued stimulation. The amplitude of the CMAP also decreased for a few minutes
      and then reached steady values. At 100-Hz stimulation, the contraction force
      decreased to 6% of the maximal force and there was a decrease in the amplitude of
      the CMAP. However, the changes in the phosphorus metabolites and pH were
      transient and recovered to the control value during the stimulation. These
      results indicated that fatigue at 1 and 100-Hz stimulation was mainly caused by
      the change in phosphorus metabolite concentrations and electrical failure,
      respectively, and that fatigue at 10-Hz stimulation might have been due to both
      of these factors. These results also indicated that electrical failure might have
      been the cause of the recovery of the phosphorus metabolites and pH during 100-Hz
      stimulation and of pH during 10-Hz stimulation.

PMID- 7805664
TI  - The ventilation, lactate and electromyographic thresholds during incremental
      exercise tests in normoxia, hypoxia and hyperoxia.
AB  - These experiments examined the effect of hypoxia and hyperoxia on ventilation,
      lactate concentration and electromyographic activity during an incremental
      exercise test in order to determine if coincident chances in ventilation and
      electromyographic activity occur during an incremental exercise test, despite an
      enhancement or reduction of peripheral chemoreceptor activity. In addition, these
      experiments were completed to determine if electromyographic activity and
      ventilation are enhanced or reduced in response to the inspiration of oxygen
      depleted and oxygen-enriched air, respectively. Seven subjects performed three
      incremental exercise tests, until volitional exhaustion was achieved, while
      inspiring air with a fractional concentration of oxygen of either 66%, 21% or
      17%. In addition, another single subject completed two tests while inspiring air
      with a fractional concentration of either 17% or 21%. During the tests,
      ventilation, mixed expired oxygen and carbon dioxide, arterialized venous blood
      and the electromyographic activity from the vastus lateralis were sampled. From
      these values ventilation, electromyographic and lactate thresholds were detected
      during normoxia, hypoxia and hyperoxia. The results showed that although
      ventilation and lactate concentration were significantly less during hyperoxia as
      compared to normoxia or hypoxia, the carbon dioxide production values were not
      significantly different between the normoxic, hypoxic and hyperoxic conditions.
      For a particular condition, the time, carbon dioxide production and oxygen
      consumption values that corresponded to the ventilation and electromyographic
      thresholds were not significantly different, but the values corresponding to the
      lactate threshold were significantly less than those for the electromyographic
      and ventilation thresholds. Comparisons between the three conditions showed that
      the time, carbon dioxide production and oxygen consumption values corresponding
      to each of these thresholds were not significantly difficult.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7805665
TI  - Neuromuscular characteristics and fatigue in endurance and sprint athletes during
      a new anaerobic power test.
AB  - The purpose of this study was to investigate neuromuscular and energy performance
      characteristics of anaerobic power and capacity and the development of fatigue.
      Ten endurance and ten sprint athletes performed a new maximal anaerobic running
      power test (MARP), which consisted of n x 20-s runs on a treadmill with 100-s
      recovery between the runs. Blood lactate concentration [la-]b was measured after
      each run to determine submaximal and maximal indices of anaerobic power (P3
      mmol.l-1, P5 mmol.l-1, P10 mmol.l-1 and Pmax) which was expressed as the oxygen
      demand of the runs according to the American College of Sports Medicine equation:
      the oxygen uptake (ml.kg-1.min-1) = 0.2 x velocity (m.min-1) + 0.9 x slope of
      treadmill (frac) x velocity (m.min-1) + 3.5. The height of rise of the centre of
      gravity of the counter movement jumps before (CMJrest) and during (CMJ) the MARP
      test, as well as the time of force production (tF) and electromyographic (EMG)
      activity of the leg muscles of CMJ performed after each run were used to describe
      the neuromuscular performance characteristics. The maximal oxygen uptake
      (VO2max), anaerobic and aerobic thresholds were determined in the VO2max test,
      which consisted of n x 3-min runs on the treadmill.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7805666
TI  - Fluid balance versus blood flow autoregulation in the elevated human limb: the
      role of venous collapse.
AB  - This study evaluated the postural vascular adjustment in the human forearm which
      may be responsible for the recent observation that transcapillary fluid balance
      is maintained above the level of the heart while blood flow decreases in a linear
      fashion. In this study further evidence was provided that a posturally graded
      profile of collapsed veins holds for both an overall increase of resistance with
      height and compensation for hydrostatic effects on capillary pressure. This was
      achieved by manipulating peripheral venous profile/volume: a proximal outlet
      resistance (upper arm cuff) was used for re-opening of collapsed distal veins. In
      test (a), 12 healthy subjects underwent recordings of fluid reabsorption rate and
      blood flow in a 20-cm segment of their forearm horizontally placed at 36 cm above
      heart level (third intercostal space). Applying upper arm cuff pressures randomly
      between 0 and 25 mmHg (0-3.33 kPa) for 15 min led to maxima of blood flow and
      reabsorption rates at inflations of 5 or 10 mmHg (0.67 or 1.33 kPa). This was
      attributed to minima in postcapillary resistance facilitating flow and reducing
      capillary pressure. In test (b) the flow-maximizing outlet resistance found was
      studied for its effect in different forearm positions (-18, 0, 18, 36, 54 cm
      relative to heart level). Blood flow then showed a shift of its maximum from
      heart level to 36 cm above heart level, while the reabsorption rate increased
      above 18-cm height--in contrast to previous findings with a free circulation. It
      was therefore concluded that the venous profile in the forearm adjusts
      postcapillary resistance in such a way that local dehydration is confined at the
      cost of blood supply. Thicker and less collapsable veins may ensure better flow
      autoregulation during impaired fluid balance--as seen in the legs.

PMID- 7805667
TI  - Heart rate threshold related to lactate turn point and steady-state exercise on a
      cycle ergometer.
AB  - The aim of this study was to investigate heart rate threshold (HRT) related
      exercise intensities by means of two endurance cycle ergometer tests using blood
      lactate concentration [La], pulmonary ventilation (VE), oxygen uptake (VO2),
      heart rate (HR) and electromyogram (EMG) activity of working muscle. Firstly, 16
      healthy female students [age, 21.4 (SD 2.8) years; height, 167.1 (SD 5.1) cm;
      body mass 62.7 (SD 7.1) kg] performed an incremental exercise test (10 W each
      minute) on an electrically braked cycle ergometer until they felt exhausted. The
      HRT and lactate turn point (LTP) were assessed by means of computer-aided linear
      regression break point analysis from the relationship of HR or [La] to power
      output. No significant difference was found between HRT and LTP for all the
      variables measured. Secondly, two endurance tests (ET) of 20 min duration were
      performed by 7 subjects. The first (ET I) was performed at an exercise intensity
      which was about 10% lower than the power output at HRT [61.2 (SD 3.1)% maximal
      oxygen uptake (VO2max)], the second (ET II) at an exercise intensity about 10%
      higher than the power output at HRT [79.2 (SD 3.4) % VO2max]. The parameters
      measured showed a clear steady state in ET I. All mean values were lower than
      values at HRT [power, 138.7 (SD 18.9) W; HR, 172.1 (SD 4.7) beats.min-1; VO2, 2.2
      (SD 0.3) l.min-1; VE, 54.0 (SD 9.1) l.min-1; [La], 3.7 (SD 1.1) mmol.l-1; EMG,
      81.1 (SD 24.0) microV] except HR which was the same.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7805668
TI  - Maximal oxygen deficit of sprint and middle distance runners.
AB  - Anaerobic energy capacity was evaluated by maximal oxygen deficit (MOD) as well
      as by blood gas and muscle biopsy variables during short exhausting running in
      six recreational (RR) and eight competitive sprint and middle distance runners
      (SMDR). On 3 days runs to exhaustion were executed. Two runs were performed at a
      treadmill gradient of 15% at speeds which resulted in exhaustion after
      approximately 1 (R15%,1 min) and 2-3 min (R15%,2-3 min), respectively. On the 3rd
      day, the subjects ran with the treadmill at a gradient of 1% at a speed which
      caused exhaustion after 2-3 min (R1%,2-3 min). The runner performance was
      assessed from 400 m [RR, median 64.8 (range 62.2-69.6) s; SMDR, median 49.4
      (range 48.5-52.0) s] and 800 m [RR, median 158.8 (range 153.3-170.2) s; SMDR,
      median 115.2 (range 113.3-123.3) s] track times. Muscle biopsies from
      gastrocnemius muscle were obtained before and immediately after R15%,2-3 min,
      from which muscle lactate and creatine phosphate (CP) concentrations, fibre type
      distribution, capillaries per fibre, total lactate dehydrogenase (LDH) activity
      and the LDH isoenzyme pattern were determined. The MOD increased with the
      treadmill gradient and duration. During both treadmill and track runs, SMDR
      performance was superior to that of RR, but no significant differences were
      observed with respect to MOD, muscle fibre type distribution, total LDH activity,
      its iso-enzyme pattern, changes in muscle lactate or CP concentrations. However,
      after treadmill runs, peak venous lactate concentration and partial pressures of
      carbon dioxide were higher, and pH lower in SMDR. Also the number of capillaries
      per muscle fibre and the maximal oxygen uptake were larger in SMDR. These
      findings would suggest that the superior performance of SMDR depended more on
      their aerobic than on their anaerobic capacity.

PMID- 7805669
TI  - Skeletal muscle vascular responses in human limbs to isometric handgrip.
AB  - Studies of whole limb blood flow have shown that static handgrip elicits a
      vasodilatation in the resting forearm and vasoconstriction in the resting leg. We
      asked if these responses occur in the skeletal muscle vascular bed, and if so,
      what is the relative contribution of local metabolic versus other mechanisms to
      these vascular responses. Blood flow recordings were made simultaneously in the
      skeletal muscle of the resting arm and leg using the Xenon-washout method in ten
      subjects during 3 min of isometric handgrip at 30% of maximal voluntary
      contraction. In the arm, skeletal muscle vascular resistance (SMVR) decreased
      transiently at the onset of exercise followed by a return to baseline levels at
      the end of exercise. In the leg SMVR remained unchanged during the 1st min of
      handgrip, but had increased to exceed baseline levels by the end of exercise.
      During exercise electromyography (EMG) recordings from nonexercising limbs
      demonstrated a progressive 20-fold increase in activity in the arm, but remained
      at baseline in the leg. During EMG-signal modelled exercise performed to mimic
      the inadvertent muscle activity, decreases in forearm SMVR amounted to 57% of the
      decrease seen with controlateral handgrip. The present study would seem to
      indicate that vascular tone in nonexercising skeletal muscle in the arm and leg
      are controlled differently during the early stages of static handgrip. Metabolic
      vasodilation due to involuntary contraction could significantly modulate forearm
      skeletal muscle vascular responses, but other factors, most likely neural
      vasodilator mechanisms, must make major contributions. During the later stages of
      contralateral sustained handgrip, vascular adjustments in resting forearm
      skeletal muscle would seem to be the final result of reflex sympathetic
      vasoconstrictor drive, local metabolic vasodilator forces and possibly neurogenic
      vasodilator mechanisms.

PMID- 7805670
TI  - Neuromuscular fatigue during prolonged pedalling exercise at different pedalling
      rates.
AB  - The purpose of this study was to estimate the differences in neuromuscular
      fatigue among prolonged pedalling exercises performed at different pedalling
      rates at a given exercise intensity. The integrated electromyogram (iEMG) slope
      defined by the changes in iEMG as a function of time during exercise was adopted
      as the measurement for estimating neuromuscular fatigue. The results of this
      experiment showed that the relationship between pedalling rate and the means of
      the iEMG slopes for eight subjects was a quadratic curve and the mean value at 70
      rpm [1.56 (SD 0.65) microV.min-1] was significantly smaller (P < 0.01) than that
      at 50 and 60 rpm [2.25 (SD 0.54), and 2.22 (SD 0.68), respectively]. On the other
      hand, the mean value of oxygen consumption obtained simultaneously showed a
      tendency to increase linearly with the increase in pedalling rate, and the values
      at 70 and 80 rpm were significantly higher than those at 40 and 50 rpm. In
      conclusion, it was demonstrated that the degree of neuromuscular fatigue
      estimated by the iEMG changes for five periods of prolonged pedalling exercise at
      a given exercise intensity was different among the different pedalling rates, and
      that the pedalling rate at which minimal neuromuscular fatigue was obtained was
      not coincident with the rate at which the minimal oxygen consumption was
      obtained, but was coincident with the rate which most subjects preferred. These
      findings would suggest that the reason why most people prefer a relative higher
      pedalling rate, even though higher oxygen consumption is required, is closely
      related to the development of neuromuscular fatigue in the working muscles.

PMID- 7805671
TI  - A new respiratory valve system for measuring oxygen uptake during swimming.
AB  - We describe a new respiratory valve system with minimal dead space, which allows
      measurement of ventilation and oxygen uptake during swimming. The device offers
      considerable advantages in efficiency and accuracy over current equipment, and
      can be used in conjunction either with a miniaturized telemetry system for oxygen
      uptake measurement or with a conventional system. The valve has a low airflow
      resistance, a small dead space (15 ml), and an electrically operating, closed
      circuit pump to remove excess water from the expiratory tube. The external form
      and the buoyancy of the valve have been hydrostatically and hydrodynamically
      designed to reduce drag and to ensure a correct mass in the water. To obtain this
      result a very sophisticated material, carbon fibre, has been utilized. Our
      studies showed that this respiratory system is ideal for obtaining valid and
      reliable values of oxygen uptake during swimming, even at high speed and in
      endurance swimming tests.

PMID- 7805672
TI  - Capacity for vasodilatation in the forearms of manual and office workers.
AB  - The aim of the present study was to investigate whether occupational physical
      work using the arms would have a local training effect on the capacity for
      vasodilatation in the forearm. The subjects were 13 installation workers, and 13
      office workers, who were similar in age, height, and body mass. The installation
      workers were exposed to heavy manual tasks during most of their workshift,
      whereas the office workers did no heavy manual exercise. The index of forearm
      capacity for vasodilatation was the plethysmograph flow response after 10 min of
      arterial occlusion (240 mmHg, 32 kPa). Systolic and diastolic blood pressure, and
      skin red cell flux (laser-Doppler) were determined together with the blood flow.
      In both groups, the dominant arm had significantly higher circumference and
      volume compared to the nondominant arm, whereas handgrip strength was similar for
      both the arms. The manual workers had greater volumes in both arms in comparison
      to the office workers, but handgrip strength did not differ between groups. In
      both groups, the peak forearm vascular conductance was higher in the dominant arm
      compared to the nondominant arm. In both forearms, the manual workers exhibited
      significantly higher peak blood flow, and peak vascular conductance than the
      office workers. No significant difference in skin blood flow was seen between the
      groups or arms. In conclusion, the forearms of the manual workers had a greater
      capacity for vasodilatation compared to the office workers suggesting a local
      vascular training effect due to frequent exposure to heavy physical work using
      hands.

PMID- 7805673
TI  - A definition and systems view of anaerobic capacity.
AB  - The purpose of this paper is both to define terms used in exercise physiology,
      i.e. anaerobic capacity, anaerobic work capacity and anaerobic potential, and
      develop a systems perspective of anaerobic capacity. Philosophical argument is
      used to support the proposed definitions and systems view, which is an approach
      to assist in the universal acceptance of such terms amongst scientific
      investigators, coaches and athletes, and provide a focus on physiological
      mechanisms associated with anaerobic capacity which may be the subject of future
      investigation.

PMID- 7805674
TI  - Effects of the menstrual cycle phase on the blood lactate responses to exercise.
AB  - The effects of menstrual cycle phase on the blood lactate response to exercise
      were examined in eumenorrheic women (n = 9). Exercise tests were performed at the
      mid-follicular and mid-luteal points in the menstrual cycle (confirmed by basal
      body temperature records and hormone levels). Blood lactates were measured at
      rest and during the recovery from exercise. Resting lactates were not different
      between the exercise tests; however, recovery lactates were significantly (p <
      0.05) lower in the luteal compared to the follicular phase. The mechanism for
      these differences is unclear, but may be related to an estrogen mediated
      increased lipid metabolism inducing a concurrent reduction in carbohydrate
      metabolism. The present findings question the use of blood lactate monitoring as
      a suitable technique to measure exercise intensity in eumenorrheic women.

PMID- 7805675
TI  - Validity of the Wescor's sweat conductivity analyzer for the assessment of sweat
      electrolyte concentrations.
AB  - The purpose of this study was to compare the "NaCl equivalent" values determined
      by the Wescor's sweat conductivity analyzer (Sweat-Chek) with the sweat Na+ and
      Cl- concentration values measured by conventional methods. The sweat was induced
      by 60-min exercise and collected by a closed-pouch collector. The "NaCl
      equivalent" values determined by the sweat conductivity analyzer (mean: 75 mmol.L
      1, range: 38 - 122, n = 72) were significantly (P < 0.05) greater than Na+
      concentration values (mean: 71 mmol.L-1, range: 24 - 123, n = 72) measured by
      flame photometry and Cl-concentration values (mean: 61 mmol.L-1, range: 18 - 100,
      n = 48) measured by coulometric titration. The difference were most accentuated
      for low concentration values. The 95% confidence-agreement intervals around the
      mean differences between methods were 11 mmol.L-1 (14%) for both Na+ and Cl-. The
      Sweat-Chek conductivity analyzer is a portable instrument which approximates the
      actual Na+ and Cl- concentrations in sweat but with a positive bias probably due
      to the other unmeasured anions present in sweat.

PMID- 7805676
TI  - Alterations of regular and mature monocytes are distinct, and dependent of
      intensity and duration of exercise.
AB  - Circulating monocytes comprise functionally distinct regular (CD14bright+) and
      mature (CD14low+) cells. Cell surface receptors were determined by three colour
      flow cytometry in 8 healthy control subjects. Compared to regular monocytes,
      mature monocytes had lower levels of the high affinity Fc gamma receptor 1
      (CD64), complement receptor 3 (CD11b), CD45RO and higher levels for HLA-DR, LFA-1
      (CD11a/CD18), interleukin-2 receptor (CD25), CD45RA and the Fc gamma receptor 3
      (CD16). Both regular and mature monocytes were measured before and up to three
      hours after four different types of exercise (Ex) in endurance trained athletes
      (n = 9-16). Immediately after anaerobic exercise of 1 min with a maximal lactate
      concentration (la max) of 12.3 (SD 1.4) mmol.1-1 and exhaustive exercise of 24
      (SD 8) min with a maximal lactate concentration (lamax) of 7.4 (SD 2.6) mmol..-1
      mature monocytes increased more than regular monocytes. Exhaustive endurance
      exercise of 87 (SD 21) min [lamax 3.7 (SD 1.0)] led to a similar increase of
      regular and mature monocytes. 15-33 min after a 100km run regular monocytes
      increased significantly, whereas mature monocytes decreased. Up to three hours
      after the end of all exercises mature monocytes fell below pre-exercise values.
      In conclusion, duration and intensity of exercise alter distinct maturation
      stages of monocytes differently. It is probable that the avidity of adhesion
      molecules like LFA-1 to their endothelial ligands is increased to enable the firm
      attachment to the endothelium.

PMID- 7805677
TI  - Prediction of individual oxygen uptake on-step transients from frequency
      responses.
AB  - Power-oxygen uptake (VO2) frequency responses can be used to predict VO2
      responses to arbitrary exercise intensity patterns. It is still an open question
      for which range of exercise intensities such computed VO2 response patterns yield
      valid predictions. In the present study, we determined the power-VO2 frequency
      response of nine sports students by means of pseudo-randomised switching between
      20 W and 80 W during upright and supine cycle exercise. Starting from a baseline
      of 20 W each subject also performed sustained step increases to 40 W, 80 W, 120
      W, and 160 W in both positions. The individual VO2 step responses were then
      compared with the expected VO2 time-courses predicted on the basis of the
      individual VO2 frequency responses. The comparison showed a close agreement for
      the 20 W-40 W and 20 W-80 W steps in both positions. With larger step amplitudes
      the VO2 kinetics became increasingly slower than the predicted VO2 time course in
      both positions. During additional ramp tests (10 W.30 s-1) whole blood lactic
      acid concentration [la-]b tended to be higher in the supine position at exercise
      intensities higher than 160 W. The mean power at 4 mmol.l-1 [la-]b amounted to
      234 (SD 32) W and 253 (SD 44) W (P < 5%) in the supine and the upright position,
      respectively. The maximal oxygen uptake relative to body mass was not found to be
      significantly different [upright, mean 57 (SD 10) ml.(min.kg)-1; supine, mean 54
      (SD 10) ml.(min.kg)-1].(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7805678
TI  - Effect of working in hot environments on respiratory air temperatures.
AB  - The purpose of this study was to obtain an accurate measure of the temperature of
      respired air of subjects working on a treadmill at various ambient temperatures
      and ambient relative humidities (RH). The experiments were conducted in an
      environmental chamber at each of four different ambient temperatures (nominally
      20, 30, 40 and 45 degrees C) and at two different ambient RH (20% and 100%) for a
      total of eight different conditions. Each experiment consisted of four tests at
      each ambient condition, these being: (A) standing quietly; (B) walking on a
      treadmill at 3 km.h-1, 0% grade; (C) walking on a treadmill at 3 km.h-1, 5%
      grade; and (D) walking on a treadmill at 5 km.h-1, 5% grade. It was found that
      under these conditions the maximum temperature of the expired air is independent
      of work rate and also ventilation rate but varies significantly with both the
      temperature and humidity of the inspired air. At low ambient RH the expired air
      temperature was [mean (SD)] 31.2 (1.3), 33.3 (0.7), 34.0 (1.7) and 35.6 (0.7)
      degrees C for ambient temperatures of 20, 30, 40 and 45 degrees C, respectively.
      At high ambient RH the expired air temperature was 32.0 (1.8), 35.3 (0.5), 37.6
      (1.2) and 41.8 (0.8) degrees C at ambient temperatures of 20, 30, 40 and 45
      degrees C, respectively. Thus the expired air temperature was higher at the
      higher ambient temperatures and ambient RH. While similar results have been
      reported before, the techniques used in this study should provide a more accurate
      measure of these effects than those previously reported.

PMID- 7805679
TI  - Abbreviated therapy for right-sided Staphylococcus aureus endocarditis in
      injecting drug users: the time has come?

PMID- 7805680
TI  - Effect of immunosuppressive therapy on the clinical presentation of
      legionellosis.
AB  - To determine whether the clinical course of legionellosis in patients treated
      with immunosuppressive agents differs from that seen in other patient groups,
      data on 52 Finnish patients with legionellosis confirmed by culture or by the
      direct immunofluorescent antibody test was reviewed. Of these patients 44% were
      immunosuppressed, 23% had other underlying diseases and 33% had no predisposing
      conditions. Among those without predisposing conditions, only Legionella
      pneumophila serogroup 1 was observed, whereas among the immunosuppressed
      patients, serogroup 6 dominated. Legionellosis was nosocomial in 73% of the
      immunosuppressed patients and in 33% of the patients with other underlying
      diseases but was travel-associated in 76% of those without predisposing factors.
      The case fatality rate (37%) was high but was not associated with preceding
      immunosuppression. These results indicate that although the serogroups and the
      sources of legionellosis differ in immunosuppressed patients compared with other
      groups, the clinical presentation is not more severe.

PMID- 7805681
TI  - Tonsil surface and core cultures in recurrent tonsillitis: prevalence of
      anaerobes and beta-lactamase producing organisms.
AB  - The bacterial flora of the tonsil surface and core was compared in patients
      suffering from recurrent tonsillitis. Surface swabs and tonsil core tissues were
      received as paired samples from 50 patients admitted for elective tonsillectomy.
      Analysis of paired samples from individual patients revealed differences in the
      bacterial flora of the tonsil core and the tonsil surface. Of 366 aerobic
      isolates, 30% grew from the surface alone, 26% from the core only and 44% from
      both sites. Of 290 anaerobic isolates, 35% grew from the surface alone, 33% from
      the core only and 31% from both sites. The total number of isolates from surface
      and core samples was similar (average 9.2 and 8.8, respectively). The range of
      species isolated was also similar for both surface and core samples, as was the
      proportion of organisms producing beta-lactamase from each site (10.7% and 9.5%,
      respectively). Eighty-two percent of patients carried beta-lactamase-producing
      organisms on either the tonsil surface or in the core tissue. A surface swab does
      not reliably reflect the types of organisms present in the tonsil core in
      individual patients. Anaerobes are a major component of tonsil surface and core
      bacterial flora in patients with recurrent tonsillitis. The high carriage rate of
      beta-lactamase-producing organisms in the tonsils should be considered when
      selecting antimicrobial therapy for persistent or recurrent tonsillitis.

PMID- 7805682
TI  - Role of bronchoalveolar lavage in mechanically ventilated patients with suspected
      pneumonia.
AB  - To determine the usefulness of samples obtained by bronchoalveolar lavage (BAL)
      in establishing the diagnosis of ventilator-associated pneumonia, quantitative
      cultures of BAL and protected specimen brush (PSB) samples obtained via
      fiberoptic bronchoscope were compared in 42 patients with suspected ventilator
      associated pneumonia. Direct examination of BAL fluid was also used to identify
      cells with intracellular organisms. Ventilator-associated pneumonia was diagnosed
      in 18 patients; a total of 39 microorganisms were recovered from BAL fluid and 29
      from PSB specimens. Cultures of 21 BAL and 23 PSB specimens were sterile.
      Quantitative BAL and PSB cultures coincided in 76% of cases. Sterile BAL and PSB
      cultures agreed in 87% of cases. Cultures were completely discordant in only
      three cases. The sensitivity of BAL for diagnosis of ventilator-associated
      pneumonia using bacterial counts of > or = 10(4) cfu/ml was 89%, and specificity
      was 100%. In 14 of the 18 patients with ventilator-associated pneumonia, the
      percentage of cells containing intracellular organisms in specimens recovered by
      BAL was 11.6% versus 0.45% in patients without pneumonia (p < 0.05). In the
      remaining four patients, all of whom had Pseudomonas aeruginosa pneumonia, no
      intracellular organisms could be detected. Using a cut-off point of > or = 5% of
      cells with intracellular organisms, the sensitivity and specificity for the early
      diagnosis of ventilator-associated pneumonia was 67% and 96%, respectively. The
      results confirm the usefulness of the quantitative BAL culture (with a cut-off at
      10(4) cfu/ml) for the diagnosis of ventilator-associated pneumonia. The
      identification of intracellular organisms in BAL fluid is a good early indicator
      of pneumonia, but the sensitivity of this technique may be lower for Pseudomonas
      aeruginosa infections.

PMID- 7805684
TI  - Analysis of Legionella pneumophila strains associated with nosocomial pneumonia
      in a neonatal intensive care unit.
AB  - A premature child received continuous mechanical ventilation in a neonatal
      intensive care unit. On day 10 of his life he developed pneumonia due to
      Legionella pneumophila serogroup 1, monoclonal subtype Bellingham. The strain was
      cultured from a tracheal secretion taken on day 10 and detected by
      immunofluorescence using monoclonal antibodies on days 10, 12 and 17. Legionella
      pneumophila serogroups 1 and 6 (10(2)-4 x 10(4) cfu/l) were cultured from both
      central and peripheral hot water systems. Monoclonal antibody testing,
      macrorestriction analysis of the genomic DNA using pulse-field electrophoresis,
      and electrophoretic alloenzyme typing showed the isolate from the child to be
      identical to the serogroup 1 strains from the hot water system. Four unrelated
      Legionella strains of the same monoclonal subgroup Bellingham were studied for
      comparison. Legionellae were also isolated from two other incubators, but no
      clinical or microbiological indications of legionellosis were found in the
      neonates hospitalised there. Serogroup 1 strains isolated from the patient and
      from the hot water system and serogroup 6 isolates from the hot water supply were
      able to multiply in cultured Acanthamoeba castellanii cells and in guinea pigs.
      The serogroup 6 strain, although prevalent in the incubators, was not found in
      any of the clinical specimens by either culture of immunofluorescence.

PMID- 7805683
TI  - Prospective evaluation of a two-week course of intravenous antibiotics in
      intravenous drug addicts with infective endocarditis. Grupo de Estudio de
      Enfermedades Infecciosas de la Provincia de Cadiz.
AB  - In a prospective study, a two-week course of antibiotics (cloxacillin 2 g/4 h
      plus amikacin 7.5 mg/kg/12 h) was evaluated in the therapy of right-sided
      infective endocarditis in intravenous drug users (IVDU). All IVDU admitted to
      hospital during the study period who fulfilled the strict criteria for diagnosis
      of infective endocarditis were analysed. A subgroup of patients with right-sided
      endocarditis caused by Staphylococcus aureus who had a good prognosis were
      selected as being eligible for the two-week course of treatment. In a total of
      139 episodes of infective endocarditis in IVDU, 72 (51.8%) cases were eligible
      for the two-week treatment. Of this group, 67 were cured, 4 needed prolongation
      of treatment to cure the infection and 1 died in hospital of respiratory distress
      syndrome on day 10 of treatment. In patients not eligible for the two-week
      treatment, the mortality was higher (24.2% versus 0.7%; p = 0.00015). Drug
      toxicity in the treated group was low. It can be concluded that administration of
      cloxacillin and amikacin parenterally for 14 consecutive days was successful in
      the therapy of right-sided endocarditis in IVDU.

PMID- 7805685
TI  - Evaluation of a passive hemagglutination assay as screening test and of a
      recombinant immunoblot as confirmatory test for serological diagnosis of Lyme
      disease.
AB  - In order to evaluate a commercially available passive hemagglutination assay
      (PHA) as a screening test for the diagnosis of Lyme disease, 173 sera were tested
      by PHA and the results compared with those obtained by an indirect
      immunofluorescence assay (IFA) and a conventional immunoblot using whole cell
      antigen (IB). Identical results were found by PHA and IFA in 80% of all cases.
      The sensitivity of the PHA was comparable to that of the IB (96%). However,
      confirmation of positive PHA results was necessary due to lack of specificity. A
      commercially available recombinant immunoblot (RIB) was compared to a
      conventional IB for its efficiency as a confirmatory assay. The rate of agreement
      was 86% of 64 sera tested positive or negative by IB. However, in order to obtain
      this high concordance of the RIB and IB, it was necessary to modify the RIB
      interpretation criteria of the manufacturer. Thus, screening of serum specimens
      by the PHA and confirmation of test results by the RIB appears to be a convenient
      test combination that allows the serological diagnosis of Lyme disease in most
      cases.

PMID- 7805686
TI  - Evaluation of an oligonucleotide probe and an immunological test for direct
      detection of toxigenic Clostridium difficile in stool samples.
AB  - A 33 basepair oligonucleotide probe, designed from the sequence of the
      Clostridium difficile toxin B gene, was evaluated for its ability to detect
      toxigenic Clostridium difficile directly in stool samples, without culture or DNA
      isolation. Two different labelling techniques were investigated: radiolabelling
      and digoxigenin-labelling. One hundred ninety-six stools were tested, with a good
      correlation (96%) obtained between the oligonucleotide probe and the gold
      standard, the cytotoxicity tissue culture assay. The sensitivity and specificity
      were 83% and 100%, respectively. In parallel, a new commercially available enzyme
      immunoassay for the detection of Clostridium difficile toxin A in stool specimens
      was investigated. In 162 samples tested, a sensitivity of 80% and a specificity
      of 98% were obtained.

PMID- 7805687
TI  - Aspergillus antigenuria compared to antigenemia in bone marrow transplant
      recipients.
AB  - The detection of galactomannan antigen in urine was investigated in 26 bone
      marrow transplant recipients using an Aspergillus latex agglutination test
      (Pastorex). After modification of the method, which was originally devised for
      serum testing, the detection limit in native urine was approximately 20 ng/ml.
      Antigen was found in 79 (36.4%) of 217 serial urine samples, compared to 40
      (11.8%) of 340 serum samples. As a rule, antigenuria preceded antigenemia and was
      more persistent. The sensitivity, specificity, positive predictive value and
      negative predictive value of antigenuria for autopsy-proven aspergillosis and
      clinically suspected Aspergillus infection were 57%, 53%, 31% and 77%,
      respectively, while those of antigenemia were 43%, 53%, 25% and 71%. It is
      concluded that urine testing is more reliable than serum testing for the
      detection of Aspergillus galactomannan. The detection of antigen, however,
      whether in serum or in urine, allows no clear distinction between Aspergillus
      infection and exposure to non-infectious Aspergillus antigens.

PMID- 7805688
TI  - An experimental model for study of Candida survival and transmission in human
      volunteers.
AB  - In order to determine the potential for cross-transmission of Candida spp.
      between health-care workers and patients, the survival of clinical isolates of
      five species of Candida on the palms of human volunteers was tested. One hundred
      microliters of a McFarland 1.0 density suspension (5 x 10(5) cfu) from an
      overnight culture of Candida albicans, Candida krusei, Candida parapsilosis,
      Candida tropicalis and Candida glabrata was used as inoculum. The degree of
      hydrophobicity of the different Candida species was also tested and did not
      influence the survival. The half-lives were brief, being 9.5, 12.4, 7.4, 12.8,
      9.6 min for Candida albicans, Candida krusei, Candida glabrata, Candida
      parapsilosis, and Candida tropicalis, respectively, but at 45 min 2.6 x 10(3) to
      3 x 10(4) organisms remained on the hands. Survival of Candida albicans for as
      long as 24 h on inanimate surfaces was observed. Transmission from one hand to a
      second hand occurred in 69% of the experiments and from the first to a third hand
      in 38%. Transmission to and from inanimate surfaces was successful in most of the
      experiments (90%). This experimental model aids in the biological study of
      Candida spp. and suggests some of the potential mechanisms of transmission.

PMID- 7805689
TI  - Antimicrobial prophylaxis in bowel surgery in The Netherlands.
AB  - The guidelines for antimicrobial prophylaxis in various types of bowel surgery
      (colorectal, biliary and gastroduodenal) in 33 antibiotic formularies used by 89
      Dutch hospitals were studied. The majority of the formularies recommended drugs
      with adequate efficacy against bacteria most frequently associated with surgical
      wound infection. Amoxicillin/clavulanic acid and first- or second-generation
      cephalosporins, with or without metronidazole, were recommended most frequently.
      Recommendations for third-generation cephalosporins and broad-spectrum
      penicillins were limited. A relatively high proportion (between 52 and 66%) of
      the formularies recommended multiple-dose regimens.

PMID- 7805690
TI  - Incidence and characteristics of urinary tract infections caused by
      Corynebacterium urealyticum (Corynebacterium group D2).
AB  - The incidence and characteristics of urinary tract infections caused by
      Corynebacterium urealyticum were studied prospectively in 20,766 urine samples.
      Corynebacterium urealyticum was isolated from 67 samples (0.32%). Twenty-four
      percent of the patients from whom Corynebacterium urealyticum was isolated showed
      mild symptoms and had no risk factors other than prolonged hospitalization and
      previous antibiotic treatment. Sixty percent of the patients had urinary tract
      related symptoms. The main risk factors were underlying urinary tract disease,
      antibiotic treatment, prolonged hospitalization and urological manipulation.
      Patients with antimicrobial treatment had a favourable clinical course, with the
      exception of two patients with encrusted cystitis.

PMID- 7805691
TI  - Trichosporon beigelii fungemia and metastatic pneumonia in a trauma patient.
AB  - Trichosporon beigelii is a fungus which usually produces cutaneous involvement in
      immunocompetent hosts, being rarely reported to cause systemic infection. A case
      of fungemia and metastatic pneumonia caused by Trichosporon beigelii in a trauma
      patient is reported.

PMID- 7805692
TI  - Association of Stomatococcus mucilaginosus with cholangitis.
AB  - The first case of cholangitis in which Stomatococcus mucilaginosus was cultured
      from bile is reported. A 64-year-old male became icteric and was shown to have
      gallstones in the gallbladder and a common bile duct stone which was removed
      endoscopically. As the patient remained icteric for a month thereafter the
      gallbladder with stones was removed. No common bile duct stone was shown by
      cholangiography perioperatively. The liver biopsy revealed cholangitis and
      Stomatococcus mucilaginosus was grown from the bile. The patient was cured by
      cholecystectomy without any antimicrobial therapy.

PMID- 7805693
TI  - Efficacy of acute phase and maintenance therapy with itraconazole in an AIDS
      patient with sporotrichosis.
AB  - An AIDS patient with sporotrichosis who improved with itraconazole therapy after
      consecutive failure of ketoconazole, saturated solution of potassium iodide,
      fluconazole and amphotericin B is presented. In addition, long-term therapy with
      high doses of itraconazole was well tolerated and effective in avoiding relapse.
      Itraconazole may be suitable for use in HIV-infected patients with
      sporotrichosis, who probably require chronic suppressive therapy to prevent
      relapse of symptomatic disease.

PMID- 7805694
TI  - Development of resistance to macrolide antibiotics in an AIDS patient treated
      with clarithromycin for Campylobacter jejuni diarrhea.
AB  - In an AIDS patient with diarrhea, identical isolates of Campylobacter jejuni
      susceptible and, later, resistant to macrolide antibiotics were isolated from
      feces before and after treatment with clarithromycin. Results of rRNA gene
      restriction analysis and serotyping suggest that development of resistance rather
      than simultaneous infection with a susceptible and a resistant strain was
      responsible for this phenomenon. This is the first report of in vivo development
      of resistance by Campylobacter jejuni in a patient treated with a macrolide for
      Campylobacter jejuni infection.

PMID- 7805695
TI  - In vitro antibacterial activity of sucralfate.
AB  - The effect of sucralfate (12.5 mg/ml) on the growth of Escherichia coli (ATCC
      25922), Enterococcus faecalis (ATCC 29212) and two isolates of Pseudomonas
      aeruginosa (ATCC 27853 and a multi-resistant clinical isolate) was studied in
      vitro at pH values of 3.0, 4.5, 6.0 and 7.4. A bacteriostatic effect of
      sucralfate was demonstrated for Pseudomonas aeruginosa at a pH of 6.0 and 7.4 and
      for Escherichia coli and Enterococcus faecalis at a pH of 6.0. The bacteriostatic
      effect was most pronounced at high pH values. Sucralfate had no bactericidal
      effect on the bacteria tested at the concentration used.

PMID- 7805696
TI  - Helicobacter pylori bacteraemia.

PMID- 7805697
TI  - Low risk of HIV transmission in rape victims.

PMID- 7805698
TI  - Detection of influenza C virus in the United Kingdom.

PMID- 7805699
TI  - Prizes!

PMID- 7805700
TI  - Supermolecular inclusion of piroxicam with beta-cyclodextrin: pharmacokinetic
      properties in man.
AB  - Piroxicam beta-cyclodextrin is a novel inclusion complex in which the piroxicam
      molecule has higher wettability and faster dissolution characteristics than plain
      piroxicam. Pharmacokinetic studies comparing piroxicam beta-cyclodextrin with
      plain piroxicam have been carried out in both patients and healthy subjects. The
      absorption rate of piroxicam from the complex, determined using tmax, absorption
      rate constant (Ka) and plasma concentrations at 15 min and 30 min post-dose, is
      considerably faster than that for plain piroxicam. This difference, that can be
      demonstrated with both tablet and sachet formulations, is still present during
      repeated dose administration and when the drugs are administered after food.
      After absorption from piroxicam beta-cyclodextrin formulations, the kinetic
      disposition of piroxicam and bioavailability parameters are identical to those
      for plain piroxicam. The more rapid rise in piroxicam plasma concentrations and
      the reduced contact time of piroxicam in the upper gastrointestinal-tract may be
      reasons for the reduced incidence of gastrointestinal complaints and
      gastrointestinal bleeding and the rapid attainment of pain relief with piroxicam
      beta-cyclodextrin. The most rapid relief of pain will be achieved using piroxicam
      beta-cyclodextrin sachets administered in the fasting state, since piroxicam is
      immediately bioavailable in this formulation and the onset of action is similar
      to that for injectable piroxicam.

PMID- 7805702
TI  - Macrocyclic molecules and their pharmacological applications.

PMID- 7805701
TI  - Effects of piroxicam-beta-cyclodextrin on the gastrointestinal tract.
AB  - Piroxicam-beta-cyclodextrin (PBC), a complex of piroxicam with beta-cyclodextrin,
      was developed with the aim of improving the hydrosolubility and bioavailability
      of piroxicam. The complex is more rapidly absorbed, with a consequent reduction
      in the time of contact of piroxicam with the gastric and duodenal mucosa. It is
      hoped that the shorter contact time might reduce the local toxicity of piroxicam,
      but it is also possible that transiently higher local concentrations of the drug
      might worsen the injury to the gastro-duodenal mucosa. Four studies have been
      conducted in healthy volunteers in order to investigate the effects of PBC on the
      gastro-intestinal tract. In 3 of these trials, all of similar design, PBC
      (containing 20 mg of piroxicam) was compared with piroxicam 20mg and placebo
      given once daily with assessment of faecal blood loss using the 51Cr-labelled red
      cell technique, and endoscopic appearance of gastroduodenal mucosa before and
      after 28 consecutive days of treatment. One study showed a significant difference
      in respect of faecal blood loss towards the end of the 4-week study period
      favouring PBC over piroxicam, while the 2 others showed comparable but non
      significant trends in favour of PBC. In a fourth study, 32 non-patient volunteers
      received either piroxicam 20mg once daily; PBC 20mg equivalence; indomethacin
      50mg twice daily; or placebo. The treatment was given double blind for 14 days.
      Endoscopy was performed and gastric potential differences were measured by
      neutral observers before and at the end of treatment. There were no significant
      differences in the endoscopic scores between the active treatment groups. The
      gastric potential difference showed greater changes with indomethacin and
      piroxicam than with placebo and PBC.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7805703
TI  - Piroxicam-beta-cyclodextrin in the treatment of acute pain of rheumatic disease.
AB  - Analgesics continue to be the mainstay of therapy in osteoarthritis. Non
      steroidal anti-inflammatory drugs (NSAIDs) play an important role, particularly
      where there is a significant inflammatory component to the osteoarthritis.
      Piroxicam-beta-cyclodextrin (PBC) is a new formulation in which piroxicam has
      been complexed with beta-cyclodextrin, a cyclic oligosaccharide. This results in
      an increase in the rate of absorption of the active compound and, consequently,
      in an earlier onset of analgesic action. PBC, like piroxicam, is administered
      once daily. PBC has been used in the treatment of osteoarthritis. In comparison
      with piroxicam, PBC showed a more rapid analgesic-anti-inflammatory action after
      the first administration in patients with active osteoarthritis. Subsequent
      evaluations at the second, fifth and last day of treatment demonstrated a
      comparable efficacy of the two drugs. The efficacy and tolerability of PBC was
      compared with other NSAIDs given intramuscularly, such as diclofenac and
      ketoprofen. The three compounds provided marked pain relief within thirty minutes
      and this increased progressively until the third to fourth hour. The efficacy of
      oral PBC was comparable to that of intramuscular diclofenac or ketoprofen. In
      comparison with metamisole PBC achieved a more rapid and sustained reduction in
      pain intensity during the first twelve hours of treatment. This rapid and marked
      reduction in pain intensity with PBC was also observed in patients with low-back
      pain when compared with etodolac. In view of its efficacy, tolerability and rapid
      onset of action, piroxicam-beta-cyclodextrin appears to be an useful analgesic
      and a prominent progress in the treatment of acute rheumatic pain.

PMID- 7805704
TI  - Rheumatic diseases--clinical experience with piroxicam-beta-cyclodextrin.
AB  - The clinical relevance of piroxicam-beta-cyclodextrin (PBC) in the long-term
      treatment of osteoarthritis and rheumatoid arthritis is reviewed. Two hundred and
      twenty-five patients--one hundred with rheumatoid arthritis and one hundred and
      twenty five with osteoarthritis--were enrolled in a double-blind, randomised,
      controlled study versus piroxicam. Drugs were administered once-daily, for twelve
      weeks. The indices of efficacy (pain intensity, severity of inflammation,
      functional impairment evaluated at 0,2,4,8 and 12 weeks showed the good analgesic
      effect of piroxicam without significant differences between its two formulations.
      Tolerance appeared to be better in the group of patients treated with PBC than in
      the one treated with piroxicam. Both the incidence and severity of side effects
      were lower for patients treated with PBC. The majority of side effects were
      related to the gastrointestinal tract. The study suggests that PBC, used in the
      long term treatment of rheumatic diseases, improves the safety of piroxicam
      without affecting its efficacy. In another study, thirty patients with chronic
      osteoarthritis were randomly assigned to receive PBC or tenoxicam daily for eight
      weeks. Both drugs effectively reduced pain, inflammation, and functional
      limitation of the affected joints. Endoscopy revealed minor post-treatment
      mucosal lesions; these tended to be less severe with PBC than with tenoxicam. The
      clinical experience in the long-term treatment of rheumatic conditions indicates
      that the microencapsulation of piroxicam as piroxicam-beta-cyclodextrin has
      provided a new drug with a superior tolerability compared to the parent compound
      without affecting its high efficacy on the symptoms of the primary disease.

PMID- 7805705
TI  - Supermolecular inclusion of piroxicam with beta-cyclodextrin: a review of its
      pharmacological properties in laboratory animals.
AB  - Piroxicam-beta-cyclodextrin is a novel NSAID; it is a supermolecular inclusion
      complex designed to improve the risk:benefit ratio of piroxicam. In animal
      studies it has been shown to be as effective as piroxicam as an anti-inflammatory
      and analgesic agent but with a more rapid onset of action and reduced
      gastropathic effects.

PMID- 7805706
TI  - Iodine-125 brachytherapy for clinically localized prostate cancer: a 5-year
      follow-up of outcome and complications.
AB  - Thirty-seven patients with clinically localized prostate cancer of all grades
      were treated by suprapubic digitally guided implantation of 125I seeds. The
      median age at the time of diagnosis was 68 years. The mean follow-up period was
      62 +/- 19 months. At last follow-up 18 patients were clinically free of disease;
      11 deaths occurred: 9 from prostate cancer and 2 from another disease.
      Complications occurred in 24 patients most commonly urgency and proctitis,
      attributable to the treatment. Four patients had severe late rectal
      complications, and 2 patients died of sepsis secondary to rectal fistulae.
      Digitally directed retropubic implantation of 125I appears inferior to other
      treatments of clinically confined prostate cancer both regarding outcome as well
      as complication rate.

PMID- 7805707
TI  - Treatment of 150 ureteric calculi with the Lithoclast.
AB  - From May 1992 to October 1993, 150 ureteral stones, impervious to piezoelectric
      extracorporeal shock wave lithotripsy (ESWL) with ultrasound localization (EDAP
      LT.01), were treated with the Lithoclast. The maximum dimensions varied from 5 to
      25 mm with a mean of 11 mm. 46 calculi were situated in the pelvic ureter, 82 in
      the abdominal ureter, and 22 were stuck in the ureteropelvic junction. There was
      no complete failure of fragmentation, but 39 abdominal calculi (48%) required
      additional treatment by ESWL due to migration of the fragments into the calyces.
      Apart from a few needle-sized perforations, ureteral tissue was not damaged by
      the Lithoclast. The use of this endoscopic lithotripter, which is highly
      efficient and painless, is, however, limited by the significant effect of
      retrograde propulsion of very mobile stones or fragments in the urinary tract.

PMID- 7805708
TI  - The malignant potential of postchemotherapy residual mature teratoma for
      disseminated nonseminomatous testicular tumors.
AB  - Flow cytometric nuclear DNA ploidy analysis was used to study 7 paraffin-embedded
      tissue blocks from 3 patients with postchemotherapy residual mature teratomas.
      All specimens contained abnormal DNA and were classified as DNA aneuploid. These
      findings indicate that despite the benign appearance of postchemotherapy mature
      teratomas, these lesions are susceptible to resume malignant behavior. Therefore,
      complete surgical removal is recommended.

PMID- 7805709
TI  - Microstructural disorders of tunica albuginea in patients affected by impotence.
AB  - The role played by the tunica albuginea in the erection mechanism seems to be
      very significant in promoting the constriction of sub-albugineal venous reticulum
      and trans-albugineal effluent veins, as well as providing an inextensible
      protective structure to the arteriolae and to the intracavernous nerves. The
      passive function exerted by the tunica albuginea is a result of its structure,
      which is rich in collagenic fibers, linked by elastic fiber bridges. The presence
      of structural disorders in the tunica albuginea of 16 patients suffering from
      psychogenic, arteriogenic and venogenic impotence is evaluated. The results
      obtained show a significant decrease in elastic fibers in the tunica albuginea of
      impotent patients compared to a control group of 5 patients with normal erection
      activity. This structural disorder could result in tunica albuginea alteration
      and, therefore, in erection insufficiency.

PMID- 7805710
TI  - Urothelial lined colocystoplasty in a sheep model.
AB  - Nineteen lambs underwent colocystoplasty using a segment of demucosalised sigmoid
      colon, and were compared to 14 control animals. Nine animals had a procedure
      which included the addition of the muscle patch to an autoaugmented bladder, and
      10 had a clam cystoplasty with the denuded colon. Six months after the procedure,
      the average compliance value for the autoaugmentation colocystoplasty bladders
      was 5.7 +/- 1.7 ml/cm H2O, compared to 6.9 +/- 2.2 ml/cm H2O for the clam
      demucosalised colocystoplasty group, and 11.0 +/- 4.8 ml/cm H2O for the control
      group. Whereas at 12 months the compliance values were 9.2 +/- 3.5, 10.7 +/- 5.1
      and 9.1 +/- 3.7 ml/cm H2O for each of the groups, respectively. The sheep colonic
      muscle tolerated the demucosalisation procedure poorly, reflected in an inflamed,
      haemorrhagic colonic segment in the animals sacrificed within 1 month; this may
      have been the reason for the poor results, and explain why the autoaugmentation
      did not improve the outcome. Colonic mucosal regrowth occurred in 5, and was
      related to the demucosalisation technique.

PMID- 7805711
TI  - Comparison of finasteride (Proscar) and Serenoa repens (Permixon) in the
      inhibition of 5-alpha reductase in healthy male volunteers.
AB  - A total of 32 healthy male volunteers (age range 20-30 years) were enrolled in a
      1-week open, randomized, placebo-controlled study comparing finasteride
      (Proscar), a 5 alpha-reductase inhibitor, with Permixon, the plant extract of
      Serenoa repens. The objective of the study was to evaluate the effect of single
      and multiple doses of the drugs on the inhibition of 5 alpha-reductase as
      assessed by serum dihydrotestosterone level determination. Following baseline
      measurements on day 1, the subjects were randomized to finasteride 5 mg once a
      day (n = 10), Permixon 80 mg x 2 twice a day (n = 11), or to placebo once a day
      (n = 11) for 7 days. Serum testosterone and dihydrotestosterone levels, were
      determined on day 1 (baseline and 12 h) and on days 2 (24 h), 3 (48 h), 4 (72 h),
      6 (120 h), and 8 (168 h). After 12 h, a single dose of finasteride 5 mg reduced
      the serum dihydrotestosterone level by 65% (p < or = 0.01). The decreases ranged
      from -52 to -60% with multiple doses of finasteride 5 mg once a day (p < or =
      0.01). As in the placebo group, there was no effect of Permixon on the serum
      dihydrotestosterone level. No significant difference was detected between
      finasteride and Permixon or between finasteride and placebo with respect to serum
      testosterone, except on days 3 and 6, respectively (p < or = 0.05). However, the
      corresponding serum testosterone levels remained within the normal ranges. These
      data confirm the efficacy of finasteride as inhibitor of 5 alpha
      reductase.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7805712
TI  - Laparoscopic adrenalectomy: comparison with open adrenalectomy.
AB  - The results of the first 6 cases of laparoscopic adrenalectomy were compared with
      the most recent 11 consecutive cases of traditional open adrenalectomy for the
      treatment of benign adrenal tumor. In both groups, all the tumors were less than
      4 cm in diameter and were removed successfully with no significant complications.
      The weight of the resected specimen and estimated blood loss were not
      significantly different in the two groups, and none of the patients needed a
      blood transfusion. Although laparoscopic adrenalectomy required a significantly
      longer operation time (median 230 min vs. 165 min for an open operation), the
      postoperative recovery estimated by the duration of restricted oral intake or
      walking was shorter, and the incidence of patients requiring postoperative
      parenteral analgesics was also significantly lower in laparoscopic adrenalectomy.
      Although the number of patients treated with the laparoscopic procedure is still
      small, these results suggest that laparoscopic adrenalectomy is a minimally
      invasive alternative to open adrenalectomy and, with further improvement of the
      operative technique and equipment, may become a more reliable and standard
      procedure for the treatment of benign adrenal tumor.

PMID- 7805713
TI  - A new colpo-needle suspension for the surgical treatment of stress incontinence:
      a 2-year follow-up.
AB  - Sixty-three patients with urinary stress incontinence underwent a new colpo
      needle suspension procedure. It differs from the other transvaginal bladder neck
      suspension procedures by using the fixed and stable Cooper ligament as the
      fixation point for the suspension sutures rather than the unstable and
      compressible anterior abdominal wall. At 2-year follow-up we obtained a 90.5%
      cure rate of urinary stress incontinence. We consider the procedure suitable for
      all patients with genuine stress incontinence. Long-term follow-up is required
      for further evaluation of this new technique.

PMID- 7805714
TI  - A modified right angle clamp for radical retropubic prostatectomy and cystectomy.
AB  - A modified version of a classic right angle clamp is described. The use of the
      new surgical instrument is advocated during radical retropubic prostatectomy and
      cystectomy for a safer and easier division of the puboprostatic ligaments and the
      dorsal vein complex as a single unit. The special shape of the clamp allows the
      surgeon to move freely and angle it beneath the pubis without hindrance from the
      bladder.

PMID- 7805715
TI  - Splenosis presenting as a left renal mass: a report of two cases.
AB  - The development of splenosis is a recognized consequence of splenic trauma. We
      present 2 cases of splenosis that were initially diagnosed as left renal cell
      carcinomas. The diagnosis of splenosis was made by technetium sulfur colloid
      scans. The clinical presentation and diagnosis of these 2 cases of splenosis
      masquerading as renal cell carcinoma are reviewed.

PMID- 7805716
TI  - Prostatic metastasis of a small cell lung cancer in a young male.
AB  - The case of a 23-year-old male with a solitary prostatic metastasis of a small
      cell lung cancer is reported. After diagnosis was established by ultrasound
      guided transrectal biopsies and bronchial lavage, the patient received 7 cycles
      of polychemotherapy according to the AEO protocol. While the pulmonary tumour
      responded with a dramatic remission, the size of the prostatic metastasis
      remained unchanged. Subsequent radiotherapy to the prostate and pelvis (59 Gy)
      did not result in tumour reduction. Shortly thereafter, the patient developed
      polytopic metastases and died 16 months after diagnosis. Even in a young male,
      the presence of a prostatic metastasis should be considered as a potential
      diagnosis if prostate biopsies are positive for a small cell carcinoma.

PMID- 7805717
TI  - Gastrocystoplasty in children: a method limited to specific cases.

PMID- 7805718
TI  - Dysregulation of interleukin-7 receptor may generate loss of cytotoxic T cell
      response in human immunodeficiency virus type 1 infection.
AB  - Virus-specific cytotoxic T lymphocytes (CTL) play a crucial role in modulating an
      immune response against human immunodeficiency type 1 (HIV-1) infection. The
      generation of effector cytotoxic cells from CTL precursors involves intricate
      interactions with antigen via T cell receptors (TcR) and soluble cytokines.
      Interleukin (IL)-7 can affect T cell maturation and differentiation. Here we
      report on a group of five HIV-1-positive individuals who tested negative for env-
      and gag-specific CTL activity. When exogenous recombinant human IL-7 was added as
      a stimulus to the cultures, none (0/5) of the CTL-negative individuals exhibited
      a CTL response. Individuals that were negative for HIV-1-specific CTL activity
      were found to lack IL-7 receptor (IL-7R) on CD8+ cells with a comparable
      reduction on CD4+ cells. Increased shedding of IL-7R in the culture supernatant
      was observed. A significant reduction in receptor number was detected by binding
      of 125I-labeled IL-7 and Scatchard analysis. The lack of IL-7R is probably not
      due to endogenous IL-7, since it was not detectable in the culture supernatants
      of the patients studied. HIV-1 proteins may cause down-modulation of IL-7R
      expression, either by producing an insufficient number of molecules or by rapid
      decay of IL-7R on T cells. These changes may alter the cells' capability to
      respond to the IL-7 growth signal, resulting in CTL failure and subsequent
      mishandling of the virus.

PMID- 7805719
TI  - Immunolocalization of intracellular interleukin-4 in normal human peripheral
      blood basophils.
AB  - The question as to whether other cell types apart from helper T lymphocytes are
      capable of producing interleukin-4 (IL-4) has gained much interest over the last
      years. Recent studies indicate that human basophils also produce IL-4, although
      direct proof is missing so far. In this study we demonstrate the presence of IL-4
      in the cytoplasm of in vitro activated human peripheral blood basophils derived
      from normal donors. Cytokine-producing cells were revealed at the single-cell
      level by intracellular immunofluorescence staining using IL-4-specific monoclonal
      antibodies. Basophils showed a characteristic, apparently granular staining
      pattern easily discerned from the eccentric dot-shaped staining pattern in
      activated T cells used in control experiments. Cell counts following priming with
      IL-3 and stimulation with polyclonal sheep anti-IgE antibody or the anaphylatoxin
      C5a revealed a significant increase in IL-4-positive basophils to about 19% as
      compared with unprimed, unstimulated control cells (6%). The amount of IL-4 in
      the supernatant of these cell preparations paralleled these observations with an
      at least five- to sevenfold increase following stimulation as compared with
      control cells (< 5 ng/ml). Using confocal scanning laser microscopy, the
      intracellular presence of IL-4 was confirmed, and the cells were identified as
      being basophils on terms of their characteristic multilobed nucleus. This
      observation was supported by double labeling studies using antibodies to IL-4 and
      to the high-affinity IgE receptor (Fc epsilon R1). Interestingly, stimulation of
      cells led to a decrease in the number of Fc epsilon R1-positive cells. The above
      results show direct evidence that IL-4 is produced by activated human basophils.

PMID- 7805720
TI  - Anti-B cell autoantibodies encoded by VH 4-21 genes in human fetal spleen do not
      require in vivo somatic selection.
AB  - We isolated immunoglobulin (Ig) VH4 genes that were rearranged in the genomic DNA
      of 160 day human fetal spleen. Productively rearranged VH 4-21 genes were cloned
      into pRTM1, a human IgM expression vector. This allowed us to generate IgM kappa
      expressing transfectomas by co-transfecting each of these constructs with pSVG-V
      kappa 3, an Ig kappa light-chain expression vector that has a variable region
      encoded Humkv325, a conserved V kappa gene that is frequently expressed early B
      cell ontogeny. We find that all transfectomas expressing IgM kappa encoded by VH
      4-21 make IgM autoantibodies reactive with i, a linear poly-N-acetyllactosamine
      determinant present on neonatal red blood cells and a B cell-restricted isoform
      of the CD45 surface molecule. In contrast, a transfectoma expressing pSVG-V kappa
      3 and pRTM1 containing a rearranged VH4-59 (V71-4) gene isolated from a chronic
      lymphocytic leukemia B cell population, designated WIL, produced IgM kappa
      antibodies that had no detectable anti-i binding activity. However, transfectomas
      expressing VH 4-21 fused onto the Ig heavy-chain third complementarity
      determining region (CDR3) of WIL are found to make anti-B cell autoantibodies
      with anti-i activity. These studies indicate that VH 4-21 genes rearranged in
      human fetal B cell ontogeny can encode anti-B cell autoantibodies with a binding
      specificity that does not require in vivo somatic selection.

PMID- 7805721
TI  - Deletion of CD4+ T cells and thymocytes by apoptosis in mouse mammary tumor virus
      (C4)-infected V beta 2 transgenic mice.
AB  - Mouse mammary tumor virus MMTV (C4) encodes a V beta 2-specific superantigen. In
      V beta 2 transgenic (TG2) mice more than 98% of peripheral T cells express V beta
      2. Infection of Tg2 mice with MMTV (C4) at birth through their mothers' milk or
      at 6-8 weeks of age by intravenous injection resulted in massive deletion of
      peripheral CD4+ T cells and suppressed thymopoiesis. The number of peripheral
      CD8+ T cells was not affected in neonatally infected mice. In older mice injected
      with MMTV (C4), splenic CD8+ T cells were significantly elevated. Suppressed
      thymopoiesis was observed in both neonatally infected and older mice injected
      with MMTV (C4). Thymocytes which expressed high level CD3 or V beta 2 were
      deleted. To determine if T cells or thymocytes were deleted through apoptosis,
      DNA fragmentation was examined by flow cytometry and diphenylamine (DPA) binding
      assay. Approximately 31% of CD4+ T cells from MMTV (C4)-infected Tg2 mice as
      compared to 6% from normal Tg2 mice contained fragmented nuclear DNA by flow
      cytometric analysis. The DPA binding assay showed significantly increased total
      soluble DNA in lymph node cells and thymocytes from MMTV (C4)-infected mice. The
      kinetics of T cell and thymocyte apoptosis correspond to their deletion,
      supporting apoptosis as the mechanism of T cell and thymocyte deletion. CD4+ T
      cell and thymocyte deletion by MMTV (C4) in Tg2 mice provides a sensitive system
      for the analysis of retrovirus superantigen-induced apoptosis.

PMID- 7805722
TI  - Stimulated natural killer cells secrete factors with chemotactic activity,
      including NAP-1/IL-8, which supports VLA-4- and VLA-5-mediated migration of T
      lymphocytes.
AB  - In vivo, natural killer (NK) cells dominate among the early invading cells in
      allografts and virus-infected tissues, and they are followed later by an influx
      of T cells. The same sequence of events was seen in our modified Boyden chamber
      assay. The migration of both CD3+/CD4+ and CD3+/CD8+ cells through fibronectin
      coated filters increased after co-culture with NK cells. The migratory response
      to a soluble factor from NK cells supernatants was predominantly chemotactic
      rather than chemokinetic. Endogenous NK cells, purified in the presence of human
      serum albumin, did not induce T cell chemotaxis, but NK cells which were purified
      in the presence of 10% fetal calf serum (FCS), or which were activated in the
      absence of FCS with 10(-4) M histamine, with 300 IU/ml interleukin (IL)-2, or
      with a combination of 10 IU/ml IL-2 and 10 micrograms/ml CD16 monoclonal antibody
      increased T cell migration by 30-70%. Both the random and chemotactic migration
      were dependent on fibronectin receptors VLA-4 and VLA-5 on T cells. About 60% of
      the chemotactic was neutralized by NAP-1/IL-8 polyclonal antibody. Northern blot
      analysis revealed IL-8 mRNA expression in highly purified, stimulated NK cells;
      dimeric IL-8 protein secreted by NK cells was detected by immunoblotting, and, in
      immunofluorescence staining IL-8 was visualized in NK cells. These observations
      suggest that NK cells, early invaders in the foci of injury, participate in the
      initiation of a specific immune response by facilitating T cell recruitment.

PMID- 7805723
TI  - T helper cell unresponsiveness: rapid induction in antigen-transgenic and
      reversion in non-transgenic mice.
AB  - T cell tolerance is usually established by clonal deletion of self-specific T
      cells in the thymus, or some times, in the periphery. Alternatively, tolerance
      may also be achieved by induction of clonal T cell unresponsiveness by a poorly
      understood mechanism called "anergy". We found that transgenic mice expressing a
      soluble form of vesicular stomatitis virus (VSV) glycoprotein (G) predominantly
      in liver and kidney exhibited normal B cell responses. VSV-G-specific T help
      independent neutralizing IgM responses were within normal ranges, but no T help
      dependent neutralizing IgG antibodies were generated upon immunization with
      recombinant VSV-G protein and recombinant vaccinia virus expressing VSV-G. This
      demonstrated absence of B cell tolerance but presence of T helper cell
      unresponsiveness. After adoptive transfer of transgenic spleen cells into
      thymectomized immuno-incompetent hosts, the unresponsive T helper cells regained
      function and switched the neutralizing IgM response to IgG, comparably to control
      T helper cells, within 7 days. Conversely, when naive non-transgenic spleen cells
      were transferred into transgenic mice, VSV-G-specific T helper cells became
      unresponsive within 3-4 days. These results suggest that VSV-G-specific T helper
      cells are rendered unresponsive within a few days in the VSV-G transgenic host
      also outside of the thymus and that this unresponsiveness was reversed by
      transfer into antigen-free recipients.

PMID- 7805724
TI  - Heterogeneity in P-glycoprotein (multidrug resistance) activity among murine
      peripheral T cells: correlation with surface phenotype and effector function.
AB  - P-glycoprotein (P-gly) is the transmembrane efflux pump responsible for multidrug
      resistance in tumor cells. Functional P-gly activity can be conveniently assessed
      microfluorometrically using the fluorescent dye rhodamine 123 (Rh123), which is
      an artificial substrate for the P-gly transporter. Here we assess P-gly activity
      in subsets of mouse peripheral T lymphocytes using the Rh123 efflux assay. Our
      data indicate that virtually all CD8+ cells extrude Rh123 efficiently, whereas
      only a subset of CD4+ cells exhibit P-gly activity. Correlation of P-gly activity
      in CD4+ cells with the expression of a panel of surface markers revealed that
      cells bearing an "activated/memory" phenotype (CD45RB-, CD44hi, CD62L-, CD25+,
      CD69+) were exclusively found in the fraction that can extrude Rh123. In contrast
      "naive" phenotype CD4+ cells (CD45RB+, CD44lo, CD62L+, CD25-, CD69-) could be
      further subdivided into two major subsets based on P-gly activity. In functional
      studies of sorted cell populations the Rh123-extruding subset of "naive" CD4+
      cells proliferated more strongly and secreted higher levels of interleukin (IL)-2
      than its Rh123-retaining counterpart when activated by a variety of polyclonal
      stimuli. Furthermore, this subset produced detectable levels of interferon (IFN)
      gamma upon stimulation but no IL-4 or IL-10. As expected, the Rh123-retaining
      "naive" subset produced only IL-2 after stimulation, whereas the "memory" subset
      produced IFN-gamma, IL-4 and IL-10 in addition to low levels of IL-2.
      Collectively, our data indicate that P-gly activity is a novel parameter that can
      be used to distinguish a subset of "preactivated" CD4+ cells that would be
      considered as naive on the basis of their surface phenotype.

PMID- 7805725
TI  - CD23/CD21 interaction is required for presentation of soluble protein antigen by
      lymphoblastoid B cell lines to specific CD4+ T cell clones.
AB  - Previous studies have documented a role for membrane-bound CD23 (the low affinity
      Fc epsilon RII) in presentation of alloantigens by B cells. The aim of the
      present study was to examine the involvement of cell surface CD23 in presentation
      of more conventional soluble protein antigens to T cells. We show that antibodies
      to CD23 and to its lymphocyte-associated second ligand, CD21, inhibit
      presentation of the cow's milk allergen casein, by autologous CD23+CD21+ B-EBV
      cell lines to casein-specific HLA-DP-restricted CD4+ T cell clones obtained from
      patients with either reaginic or enterophatic forms of cow's milk protein
      intolerance. Maximal inhibition was achieved when the antibodies were added at
      the initiation of the culture. The absence of specific inhibition by an anti-DR
      alpha monoclonal antibody (mAb) argues against a steric hindrance phenomenon
      impeding access of the T cell receptor to major histocompatibility complex class
      II molecules. Rather, anti-CD23 and anti-CD21 mAb-induced inhibition of antigen
      presentation seems to affect at least partly, heterotypic conjugate formation
      through CD23/CD21 interaction. Double immunofluorescence labeling of the T cell
      clones and antibody inhibition of T/B conjugate formation shows that functional
      CD23 and CD21 molecules are induced on T cells following contact with B-EBV cell
      lines. Taken together, these data indicate that CD23/CD21 interactions between T
      and B cells are required for presentation of soluble protein antigens by B-EBV
      cell lines to specific CD4+ T cells. The potential implications of these findings
      for allergen-specific T cell activation are discussed.

PMID- 7805726
TI  - Shared amino acid sequences in the ND beta N and N alpha regions of the T cell
      receptors of tumor-infiltrating lymphocytes within malignant glioma.
AB  - The purpose of this study was to assess the V-(D)-J junctional region of the T
      cell receptor (TCR), the CDR3 region, which is responsible for glioma-specific
      antigen contact in alpha beta TCR-mediated recognition. We sequenced the TCR
      alpha and beta chains of V alpha 7, and V beta 13.1 cDNA derived from tumor
      infiltrating lymphocytes (TIL) of 12 glioma patients and also the corresponding
      clones from the patients' peripheral blood lymphocytes (PBL). A shared V beta
      13.1 DJ sequence of the CDR3 region, ND beta N, was demonstrated in 49 of 66 V
      beta 13.1+ clones (74.2%) from the glioma TIL, whereas only 4 of 33 clones
      (12.1%) were observed in the V beta 13.1+ clones from the PBL (p < 0.001). A
      common VDJ sequence, FCASS (V beta 13.1)-YRLPWGTSDS (ND beta N)-GELFF (J beta
      2.2), was observed not only in the gliomas from each patient, but also among all
      the patients with a preference for V beta 13.1. In contrast, the amino acid
      sequences of the V beta 13.1+ PBL clones were diverse and random. Next, we
      sequenced subclones from other V beta subfamilies randomly selected to compare
      their VDJ region rearrangements (V beta 3 and V beta 5.1). In contrast to V beta
      13.1, the amino acid sequences of these junctional regions were completely
      different in these subclones. The V-J junctional region of the alpha chain is
      dominated by a few clones in some patients, and no shared amino acid sequences
      were detected in the TCR V alpha junctional region. However, in the N alpha
      region of the V alpha 7-bearing TIL clones, arginine was used in 27 of 44 clones
      (61.4%) compared to only 3 of 12 clones from the PBL (p < 0.05). These results
      are consistent with the hypothesis that a clonal expansion/accumulation of glioma
      lineage-specific T cells occurred in vivo at the tumor site and that these T
      cells may be recognizing glioma-specific antigens.

PMID- 7805727
TI  - Co-stimulation by anti-immunoglobulin is required for B cell activation by
      CD40Llow T cells.
AB  - During cognate B:T interactions, B cells encounter antigen (Ag) through surface
      immuno-globulin (sIg) and present antigenic peptides to T helper (Th) cells.
      However, most in vitro systems used to study contact events involved in the
      delivery of T help for B cells circumvent the requirement for T cell Ag
      specificity by using anti-CD3/T cell receptor (TcR) monoclonal antibodies (mAb)
      to activate T cells. To study the role of sIg engagement in the responsiveness of
      B cells to T help, we pre-treated small resting B cells with soluble anti-kappa
      mAb prior to contact with an activated Th1 clone. By reducing the concentration
      of anti-TcR mAb we obtained low levels of CD40 ligand (CD40Llow) on Th cells,
      comparable to those expressed by lymph node T cells activated in vitro (ex vivo T
      cells). In contrast to untreated B cells, which did not respond to CD40Llow Th,
      anti-Ig-treated B cells responded strongly. Low buoyant density B cells also
      responded to CD40Llow Th cells. There was no B cell response to resting Th cells.
      mAb against CD54/intercellular adhesion molecule-1 or major histocompatibility
      complex (MHC) class II completely inhibited B cell responses to CD40Llow Th1
      cells, equivalent to the effects of blocking CD40 interactions. This contrasts
      with mAb blocking responses to CD40Lhigh Th, where CD40 effects predominate. Our
      data show that sIg engagement is necessary for the induction of B cell response
      to CD40Llow Th cells. Anti-CD3-activated ex vivo T cells that were also CD40Llow
      did not provide help to small resting B cells, but did induce responses from sIg
      stimulated B cells. Thus, our data support a requirement for sIg signaling in
      physiological B cell activation, and further confirm previous work showing CD40
      ligation to be necessary but not sufficient for delivery of T help to B cells.

PMID- 7805728
TI  - Activation-induced proteolysis of cytoplasmic domain of zeta in T cell receptors
      and Fc receptors.
AB  - The CD3-T cell receptor (TCR) complex on T cells and the Fc gamma receptor type
      III (Fc gamma RIII)-zeta-gamma complex on natural killer cells are functionally
      analogous activation receptors that associate with a family of disulfide-linked
      dimers composed of the related subunits zeta and gamma. Immunochemical analysis
      of receptor complexes separated on two-dimensional diagonal gels allowed the
      identification of a previously uncharacterized zeta-p14 heterodimer. zeta-p14 is
      a component of both CD3-TCR and Fc gamma RIII-zeta-gamma. Peptide mapping
      analysis shows that p14 is structurally related to zeta, suggesting that it is
      either: (i) derived from zeta proteolytically or (ii) the product of an
      alternatively spliced mRNA. The observation that COS cells transformed with a
      cDNA encoding zeta express zeta-p14 supports the former possibility. The
      expression of CD3-TCR complexes including zeta-p14 increases following activation
      with phorbol 12-myristate 13-acetate or concanavalin A, suggesting that
      proteolysis of zeta may contribute to receptor modulation or desensitization.

PMID- 7805729
TI  - The murine interleukin-2 receptor gamma chain gene: organization, chromosomal
      localization and expression in the adult thymus.
AB  - Defects in the interleukin-2 receptor gamma (IL-2R gamma) chain in the man result
      in an X-linked severe combined immunodeficiency, SCIDX1, characterized by an
      absence of T-cell differentiation. This phenotype may result from pertubations in
      IL-2, IL-4-, IL-7- or IL-15-mediated signaling, as the IL-2R gamma chain forms an
      integral component of these receptor systems. We have isolated and characterized
      cDNA and genomic clones for the murine IL-2R gamma. The gene (Il2rg) is well
      conserved between mouse and man with respect to overall structure and size, and
      contains regions of high conservation in the promoter region as well. Il2rg maps
      to mouse X chromosome region 40, in a region of synteny with human Xq12-13.1. We
      have also explored the expression of the IL-2R gamma during thymocyte
      development. IL-2R gamma transcripts are detected in the earliest thymocyte
      precursor cells and persist throughout intrathymic development into the mature
      peripheral compartment. Genomic clones for the murine IL-2R gamma will allow for
      further studies on the regulation and function of this gene in vivo.

PMID- 7805730
TI  - Maternal immunization modulates the primary immune response to 2-phenyl-oxazolone
      in BALB/c mice.
AB  - The development of the antibody repertoire in newborn mice is greatly influenced
      by idiotype network interactions. It has been demonstrated that anti-idiotypic
      antibodies either directly injected or transferred from the mother may alter the
      repertoire for life. For an elucidation of the underlying mechanisms we have
      analyzed the primary immune response to 2-phenyl-5-oxazolone (phOx) coupled to
      chicken serum albumin (CSA) in BALB/c mice after complete disappearance of
      maternal antibodies which originated from different stages of affinity
      maturation. Depending on the serum titers of the mothers after primary (1 degree
      mo), secondary (2 degrees mo) or tertiary (3 degrees mo) immunization, maternal
      anti-phOx IgG persisted in F1 mice for up to 9 months. In addition, F1 mice born
      to 2 degrees mo developed--even without immunization--an anti-phOx IgM titer
      which reached levels similar to an antigen-induced primary response. An
      enhancement of the early primary anti-phOx as well as anti-CSA response was seen
      in F1 mice born from 1 degree mo, whereas the response was delayed when born to 2
      degrees mo and 3 degrees mo. The antibody titers in the latter group of mice
      remained at a lower level for 3 months. In contrast, mice of the F2 generation
      which received a smaller amount of the same collection of maternal antibodies as
      F1 mice from 3 degrees mo exhibited a quite different primary response: (i) They
      showed an earlier onset in their anti-CSA response. (ii) Whereas normally a
      plateau in antibody titer was reached by the 4th weak after immunization, in 55%
      of the F2 mice a prolonged increase of the anti-phOx and anti-CSA antibody titers
      was observed. At 12 weeks after antigenic challenge, titers reached plateau
      levels of 6 x 10(5) which were never before seen in a primary phOx or CSA
      response. Thus, depending on its own immunological experience, the maternal
      immune system induces a state of memory in the offspring which results in a
      faster and/or enhanced immune response in the F1 and F2 [corrected] generations.

PMID- 7805731
TI  - A peptide encoded by human gene MAGE-3 and presented by HLA-A2 induces cytolytic
      T lymphocytes that recognize tumor cells expressing MAGE-3.
AB  - The human MAGE-3 gene is expressed in many tumors of several histological types
      but it is silent in normal tissues, with the exception of testis. Antigens
      encoded by MAGE-3 may, therefore, be useful targets for specific anti-tumor
      immunization of cancer patients. We reported previously that MAGE-3 codes for an
      antigenic peptide recognized on a melanoma cell line by autologous cytolytic T
      lymphocytes (CTL) restricted by HLA-A1. Here we report that the MAGE-3 gene also
      codes for another antigenic peptide that is recognized by CTL restricted by HLA
      A2. MAGE-3 peptides bearing consensus anchor residues for HLA-A2 were synthesized
      and tested for binding. T lymphocytes from normal individuals were stimulated
      with autologous irradiated lymphoblasts pulsed with each of three peptides that
      showed strong binding to HLA-A2. Peptide FLWGPRALV was able to induce CTL. We
      obtained CTL clones that recognized not only HLA-A2 cells pulsed with this
      peptide but also HLA-A2 tumor cell lines expressing the MAGE-3 gene. The
      proportion of melanoma tumors expressing this antigen should be approximately 32%
      in Caucasian populations, since 49% of individuals carry the HLA-A2 allele and
      65% of melanomas express MAGE-3.

PMID- 7805732
TI  - T cell receptor gamma delta repertoire in HIV-1-infected individuals.
AB  - While V gamma 9/V delta 2 cells dominate among peripheral blood gamma delta T
      cells in healthy adults, the majority of gamma delta T cells in most HIV-1
      infected individuals express V delta 1. We asked whether these elevated levels of
      V delta 1 T cells were due to clonal expansion. Three-color flow cytometry with
      monoclonal antibodies against V gamma 2/V gamma 3/V gamma 4, V gamma 4 and V
      gamma 9 was used to investigate V gamma usage in 27 patients with elevated
      numbers of V delta 1 T cells. While the relative proportion of V gamma 9 cells
      among gamma delta T cells was significantly reduced in HIV-1+ individuals (10 +/-
      11% vs. 80 +/- 17%, p < 0.001), the fraction of gamma delta T cells using V gamma
      5 or V gamma 8 was significantly increased (54 +/- 15% vs. 7 +/- 11%, p < 0.001).
      In 1 patient, 76% of the V delta 1 cells expressed V gamma 2 or V gamma 3,
      suggesting clonality of the V delta 1 population. In line with this assumption,
      analysis of the V delta 1-J delta junctional regions by reverse transcription
      polymerase chain reaction (RT-PCR) resulted in products of only one junctional
      length, as demonstrated by electrophoresis on denaturing gels, and 12 out of 16
      (75%) in-frame junctional sequences were identical in this patient. In other HIV
      1+ patients, RT-PCR resulted in products of several distinct sizes, also
      indicating a highly restricted repertoire. After sequencing the V delta 1-J delta
      junctional regions of 3 additional patients, we found repeated but patient
      specific in-frame junctions accounting for 10-30% of the sequenced clones.
      However, limited V delta 1-J delta junctional diversity was also seen in healthy
      donors. RT-PCR products from 10 healthy individuals resulted in distinct bands on
      denaturing gels. In 1 of them exhibiting a single prominent band, 10 out of 17
      (58%) sequenced junctions were identical. Two other healthy donors displayed 2/14
      and 5/18 identical junctional sequences, respectively. Taken together, our
      results reveal significant alterations of V gamma usage in HIV-1+ patients, while
      the V delta 1 junctional repertoire is similarly restricted in HIV-1+ and HIV-1-
      individuals. Therefore, these data argue against an obligatory clonal expansion
      of V delta 1-expressing cells during HIV-1 infection.

PMID- 7805733
TI  - Increased susceptibility of mice infected with Schistosoma mansoni to recombinant
      vaccinia virus: association of viral persistence with egg granuloma formation.
AB  - BALB/c mice infected 7 weeks previously with Schistosoma mansoni and challenged
      with a recombinant vaccinia virus vPE16 expressing the human immunodeficiency
      virus envelope protein gp160 show a marked delay in hepatic viral clearance as
      compared to mice infected with vPE16 alone. This increase in viral persistence is
      accompanied by reduced gp120-specific Th1-associated cytokine responses as well
      as by impaired cytotoxic T lymphocyte (CTL) activity against targets expressing
      epitopes of the same antigen. To investigate the contribution of these defects to
      the observed delay in clearance of recombinant vaccinia virus, animals were
      challenged with vPE16 at different times following S. mansoni infection, and
      virus titers in tissues and viral-specific immune responses were measured
      simultaneously in the same animals. While normal resolution of virus occurred in
      schistosome-infected mice prior to parasite egg deposition, persistence within
      the liver was observed in animals challenged during the onset and peak phase of
      granuloma formation (6 to 8 weeks after S. mansoni infection). At later times,
      when schistosomiasis is in its chronic phase, normal viral clearance returned.
      This time course of viral resolution correlated in part with the observed pattern
      of decreased Th1 cytokine production toward viral antigens but was clearly less
      temporally related to the defect in virus-specific CTL activity.
      Immunohistochemical staining of liver sections from vaccinia/S. mansoni co
      infected mice with polyclonal anti-vaccinia antibodies revealed that viral
      epitopes are localized primarily within granulomas. These experiments suggest
      that egg granulomas, by providing a microenvironment for viral expression, in
      combination with the cytokine imbalance present during schistosome infection, can
      promote the expansion of vaccinia virus and possibly other viral agents.

PMID- 7805734
TI  - IgG isotype distribution of local and systemic immune responses induced by
      influenza virus infection.
AB  - The IgG isotype profile of the influenza virus-specific immune response was
      studied by quantitation of serum antibody (Ab) levels in correlation with the
      enumeration of antibody-secreting cells (ASC) detected in the lung, spleen,
      mediastinal lymph nodes (MLN), Peyer's patches and bone marrow (BM). Distinct
      isotypic patterns for serum Ab and Ab produced by cells present at or close to
      the site of infection were found after primary or repeated infections. An
      elevated number of IgM ASC was found after primary challenge in the spleen, lung
      and MLN. In contrast, the site of IgA and IgG production is restricted to the
      lung and lymph nodes draining the site of infection. In these organs IgA, IgG2a
      and IgG1 ASC are found as a result of primary virus infection while viral
      challenge induces mostly activation of IgA-producing cells and secretion of IgA
      to the lung lavage. In contrast, the majority (80-90%) of Ab detected in the
      serum belong to the IgG2a subclass and their serum level is maintained at a high
      level during the whole period of the response. The relative level of virus
      specific serum IgG2a in correlation with the production of IgG2a Ab found
      predominantly in MLN and lung is highly dependent on the viral dose used for
      priming or challenge. As IgG2a ASC can be detected at relatively low numbers in
      the spleen and BM these results suggest that the production of the dominant IgG2a
      isotype of serum Ab occurs close to the viral challenge site. These data,
      however, point to distinct isotypic regulation in systemic versus local virus
      specific Ab responses.

PMID- 7805735
TI  - CD8+ T cell-mediated protection against an intracellular bacterium by perforin
      dependent cytotoxicity.
AB  - Growth of Listeria monocytogenes is mainly controlled by macrophages, which are
      activated by specific T cells. A potential role of CD8+ T cells by direct lysis
      of infected cells was investigated in perforin-deficient mice generated by
      homologous recombination. The absence of perforin-mediated cytotoxicity resulted
      in delayed clearance of Listeria from the spleen but not the liver after primary
      infection, overall susceptibility to Listeria however was not increased.
      Protection against a secondary infection was drastically impaired in perforin
      deficient mice. Adoptive transfer of immune spleen cells to recipients revealed
      that anti-Listeria protection by CD8+ T cells from perforin-deficient versus
      normal mice was about 10-fold reduced in livers and about 100-fold reduced in the
      spleen of recipients. CD4+ T cells from immune control and perforin-deficient
      mice conferred comparable protection. These results indicate that the protective
      effect of CD8+ T cells against an intracellular bacterium mainly evident in
      secondary infection is mediated by a perforin-dependent pathway, presumably
      cytotoxicity, and less by other direct or indirect effector mechanisms.

PMID- 7805736
TI  - T cell receptor V beta 8.2 gene germ-line transcription: an early event of
      lymphocyte differentiation.
AB  - Rearrangement of the T cell antigen receptor (TCR) beta chain genes is highly
      regulated in both a developmental and a tissue-specific manner. T cell precursors
      originate from the yolk sac or fetal liver during gestation and from the bone
      marrow during adulthood. They initiate the recombination of TCR genes primarily
      during differentiation in the thymus. It has previously been suggested that
      transcription of immunoglobulin genes in germ-line configuration is linked to
      recombination events within these loci. Here, we examine whether germ-line
      transcription of TCR variable genes coincides with their rearrangement or whether
      it marks even earlier stages of T lymphocyte development. During gestation, we
      found V beta 8.2 germ-line transcripts in the fetal liver and the fetal thymus,
      but not in the yolk sac. This transcription precedes V beta 8.2 to D beta J beta
      rearrangement. In adult animals, we found these transcripts in the thymus, the
      spleen, the liver and the bone marrow. However, in the liver, this transcription
      is dependent on the presence of mature lymphocytes. This transcription does not
      happen in non-lymphoid cells. In the B lymphocyte lineage, V beta 8.2 germ-line
      transcripts are detected only in the earliest stages of differentiation (pre-pro-
      and pro-B cells), but not in pre-B cells and mature B lymphocytes. Altogether,
      our results show that transcription of the unrearranged V beta 8.2 gene is an
      early event of lymphocyte development, taking place in lymphocyte precursors,
      long before V beta 8.2 rearrangement.

PMID- 7805737
TI  - Peyer's patch CD8+ memory T cells secrete T helper type 1 and type 2 cytokines
      and provide help for immunoglobulin secretion.
AB  - Analysis of cytokine gene expression by reverse transcription-polymerase chain
      reaction (RT-PCR) demonstrated high spontaneous levels of transcripts for
      multiple cytokines in murine Peyer's patches (PP) compared to spleen and
      peripheral lymph nodes. This is consistent with the presence of active germinal
      centers in PP and their continuous exposure to lumenal antigen including
      bacterial endotoxin. RT-PCR analysis of cytokine transcripts in purified PP T
      cell populations revealed the presence of transcripts for interleukin-4 (IL-4),
      IL-5 and IL-10 in addition to interferon-gamma (IFN-gamma) in CD8+ cells purified
      by flow cytometry. The majority of PP CD8+ T cells were also CD45RBlo (MB23G2-),
      suggesting that these cells were activated/memory cells. CD8+ cells in spleen and
      mesenteric lymph nodes (MLN) were predominantly CD45RBhi (MB23G2+) consistent
      with a resting/naive phenotype. PP and MLN CD8+ T cells also secreted IL-5 and IL
      10 when stimulated with anti-CD3 monoclonal antibody and when co-cultured with PP
      B cells enhanced secretion of both IgG and IgA. These studies suggest that CD8+ T
      cells at mucosal sites secrete T helper type 2 cytokines and can provide
      functional help for B cells in these tissues.

PMID- 7805738
TI  - T lymphocyte-mediated antiviral immune responses in mice are diminished by
      treatment with monoclonal antibody directed against the interleukin-2 receptor.
AB  - Blocking the interleukin-2 receptor's alpha-chain in lymphocytic choriomeningitis
      virus-infected mice by treatment with monoclonal antibodies diminished the
      increase of numbers of CD8+ T lymphocytes in spleens and prevented CD8+ T
      lymphocyte-mediated virus clearance from organs as well as generation of virus
      specific cytotoxic T lymphocytes. Also, the CD8+ T cell-mediated early phase of
      the delayed-type hypersensitivity footpad swelling reaction was decreased. The
      same treatment had no effect on the number of CD4+ spleen T lymphocytes, which,
      however, did not enlarge during infection, but these cells' heightened DNA
      synthesis and cytokine production were reduced by antibody treatment; yet the
      generation of antiviral antibodies remained unaffected, and the CD4+ T lymphocyte
      mediated second part of the footpad reaction was somewhat augmented. We conclude
      that blocking of the interleukin-2 receptor by antibody in lymphocytic
      choriomeningitis virus-infected mice diminishes both CD8+ and CD4+ T cell
      mediated antiviral immune responses, the former more than the latter.

PMID- 7805739
TI  - Expression of Bruton's tyrosine kinase protein within the B cell lineage.
AB  - Defects in the gene encoding Bruton's tyrosine kinase (Btk), normally expressed
      in B cells, cause X-linked agammaglobulinemia (XLA). The phenotype of XLA is
      characterized by a lack of circulating B cells and immunoglobulin. It has been
      suggested that B cell maturation from the pre-B cell stage to more mature stages
      is dependent on the appropriate expression of this gene. The Btk mRNA is
      expressed in B cells and myeloid cells, but protein expression in relation to B
      cell maturation has not been determined. Moreover, expression of the Btk protein
      has so far only been investigated in human Epstein-Barr virus-transformed B cell
      lines, and in murine splenocytes and B cell lines. We have developed an antiserum
      which recognizes the human Btk protein and shown that normal human tonsillar B
      cells, peripheral blood monocytes and myeloid cells express the protein, whereas
      tonsil-derived T cells do not. We also show that the protein is present in early
      and mature human B cell lines, but is absent in terminally differentiated plasma
      cell lines. Furthermore, expression is reduced or absent in three B lineage cell
      lines derived from two patients with defined genetic mutations in Btk and
      suffering from XLA.

PMID- 7805740
TI  - Low-level infection with Trichuris muris significantly affects the polarization
      of the CD4 response.
AB  - Resistance and susceptibility to the intestinal nematode Trichuris muris has been
      shown to be dependent upon the induction of T helper type 2 (Th2) or Th1 cells,
      respectively. This study demonstrates that in a normally resistant strain of
      mouse, i.e. BALB/K which mounts a dominant Th2 response, sub-threshold levels of
      infection (< 40 eggs) can survive and become sexually mature adult worms (10-20
      adults). The immunological basis of this phenomenon was found to be a
      dramatically altered polarization of the CD4 response. The Th2-response
      characteristic of this strain of mouse infected with T. muris was shown to be
      significantly down-regulated as assessed by in vitro cytokine production
      [interleukin (IL)-4, IL-5 and IL-9]. In contrast, Th1 parameters of infection
      such as in vitro interferon-gamma production and the presence of parasite
      specific IgG2a were greatly up-regulated in these mice.

PMID- 7805741
TI  - Effect of interferon-gamma on antigen processing in human monocytes.
AB  - The effect of interferon-gamma (IFN-gamma) on the ability of human monocytic
      cells to process exogenous (major histocompability complex class II) antigens was
      investigated. The processing (i.e. protein degradation) of antigens that were
      internalized via Fc gamma receptor (Fc gamma R) was followed for various times
      after treatment of cells with IFN-gamma. THP-1 cells that had been treated with
      IFN-gamma for 4 h degraded antigen, internalized as an immune complex, at an
      enhanced rate. After 24 h of IFN-gamma treatment the rate of processing was
      similar to untreated cells. Unexpectedly, in cells which had been treated for 48
      72 h there was a significant decrease in the rate of processing of the exogenous
      antigen. These effects were not due to changes in the rate of internalization of
      immune complex. The inhibition of the rate of processing was independent of the
      type of antigen, was dependent on the dose of IFN-gamma, and also occurred with
      normal human peripheral monocytes. Analysis of the degraded peptides by high
      pressure liquid chromatography indicated that some of the peptides generated in
      the IFN-gamma-treated cells were both quantitatively and qualitatively different
      from the peptides generated in untreated cells. These data suggest that IFN-gamma
      modulates the way in which antigens, internalized through Fc receptors as immune
      complexes, are processed. Additionally, the results imply that decreases in the
      rate of antigen processing may lead to more efficient antigen presentation.

PMID- 7805742
TI  - Involvement of a serine protease in the synthesis of platelet-activating factor
      by endothelial cells stimulated by tumor necrosis factor-alpha or interleukin-1
      alpha.
AB  - It has been shown that production of platelet-activating factor (PAF, 1-O-alkyl-2
      acetyl-sn-glycero-3-phosphocholine) by endothelial cells (EC) stimulated with
      tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 alpha requires the
      synthesis of new proteins and is regulated by anti-proteinases. Here, we
      demonstrate that TNF-alpha and IL-1 alpha induce the expression by EC of a 34-kDa
      diisopropyl fluorophosphate-binding protein immunoprecipitated by an anti-human
      elastase antibody. This protein is released in the medium and cleaves the
      chromogenic substrate N-methoxysuccinyl- Ala-Ala-Pro-Val p-anilide, which is
      specific for elastase. The generation of this elastase-like protein seems to be
      important for the synthesis of PAF induced by TNF-alpha and IL-1 alpha, as
      suggested by the following observations: (a) it precedes the synthesis of PAF;
      (b) the inhibitors of serine protease and anti-human elastase antibody prevent
      the synthesis of PAF and the activation of 1-O-alkyl-2-lyso-glycerophosphocholine
      acetyl-CoA: acetyltransferase, which is a key enzyme of the PAF remodelling
      pathway; (c) elastase, at concentrations similar to that detectable in the medium
      of cytokine-activated EC, elicits a rapid synthesis of PAF by EC. High
      performance liquid chromatography-tandem mass spectrometric analysis of bioactive
      PAF demonstrates that the molecular species produced after stimulation of EC with
      TNF-alpha, IL-1 alpha or elastase are similar, with a predominant synthesis of
      the alkyl species. These results indicate that TNF-alpha and IL-1 alpha stimulate
      the production of a serine protease which is critical in the activation of
      enzymes involved in PAF synthesis, suggesting the potential involvement of this
      mechanism in the regulation of EC functions.

PMID- 7805743
TI  - Inhibition of the development of immediate hypersensitivity by staphylococcal
      enterotoxin B.
AB  - We investigated the ability of staphylococcal enterotoxin B (SEB) to modify the
      immediate hypersensitivity response induced in BALB/c mice following
      sensitization to ovalbumin (OVA), a response mediated by OVA-reactive V beta 8 T
      cells. Mice were sensitized by skin painting with OVA every second day over a
      period of 2 weeks. SEB, a potent activator of V beta 8+ T cells, was administered
      at the same site where OVA was applied (skin of the lower abdomen) following two
      different protocols. In protocol (A) SEB was injected intradermally 1 day before
      painting with OVA and on day 7; in protocol B, SEB was injected each time OVA was
      applied to the skin (eight times). SEB (but not SEA) altered the development of
      immediate hypersensitivity to OVA, as demonstrated by the reduction in allergen
      specific IgE, decreased OVA-specific immediate skin test responsiveness, and
      prevented the development of increased airways responsiveness after bronchial
      challenge with OVA. Injections of SEB did not alter the proliferative responses
      of local draining lymph node cells or spleen mononuclear cells to OVA, indicating
      that administration of SEB did not inhibit the sensitization of OVA, but shifted
      the immune response away from an immediate type response (IgE/IgG1) to IgG2a,
      IgG2b and IgG3. Although both protocols of SEB treatment did not lead to a major
      deletion of the V beta 8 T cell population, they did reduce the proliferative
      response of V beta 8+ T cells to OVA. These data indicate that the bacterial
      toxin SEB is capable of modifying the immediate hypersensitivity response induced
      by OVA by altering the functional capacity of antigen-reactive V beta 8 T cells.

PMID- 7805744
TI  - Elongated peptides, not the predicted nonapeptide stimulate a major
      histocompatibility complex class I-restricted cytotoxic T lymphocyte clone with
      specificity for a bacterial heat shock protein.
AB  - The peptides recognized by an H-2Db-restricted CD8 cytotoxic T lymphocyte (CTL)
      clone which is specific for the 60-kDa mycobacterial heat shock protein (hsp) and
      cross-reacts with stressed host cells were characterized. None of the
      nonapeptides from hsp60 conforming to the H-2Db binding motif were able to
      sensitize target cells for lysis by this CTL clone. Sequence analysis of the
      stimulatory fraction from a trypsin digest of hsp60, together with synthetic
      peptide studies, defined a cluster of overlapping epitopes. Carboxy-terminal
      extension by at least one amino acid of the nonamer predicted to bind best to H
      2Db was essential for CTL recognition. Two such elongated peptides, a 10-mer and
      a 12-mer stimulated the clone at similarly low concentrations in the 100 pM
      range. We assume that these two peptides comply best with the natural epitope. In
      contrast, the 11-mer was inactive. The stimulatory 10-mer bound to H-2Db with an
      efficacy similar to that of the nonapeptide corresponding to the H-2Db motif, as
      revealed by peptide induced major histocompatibility complex (MHC) surface
      expression on RMA-S cells and competitive blocking of epitope recognition by the
      nonamer. Binding of these carboxy-terminally extended peptides to the MHC groove
      can be explained by anchoring through the amino acid residue Asn in position 5 of
      the peptide and by intrusion of the hydrophobic carboxy-terminal Ala (10-mer) or
      Leu (12-mer), but not Gly (11-mer), into the hydrophobic pocket of the H-2Db
      cleft. Because the carboxy-terminal part is thus larger than predicted, this
      region of the peptide may arch up from the binding groove. We assume that
      recognition of steric components of the MHC/peptide complex broaden the range of
      epitope specificity for a single T cell receptor. This flexibility not only
      promotes recognition of several overlapping peptides from a single antigen, but
      may also increase the chance of cross-reaction with similar peptides from
      unrelated proteins, including autoantigens. Consistent with this latter
      assumption, the T cell clone cross-recognizes mycobacterial hsp60 and stressed
      host cells.

PMID- 7805745
TI  - Freshly isolated mouse 4F7+ splenic dendritic cells process and present exogenous
      antigens to T cells.
AB  - The antibody 4F7 was reported to recognize an epitope expressed on dendritic
      cells (DC) from various tissues. To study the ability of splenic 4F7+ dendritic
      cells to process antigen for presentation to CD4+ T cells, DC were enriched using
      a separation procedure avoiding overnight culture which could lead to an altered
      phenotype. These DC were used as antigen-presenting cells (APC) in stimulation
      cultures of major histocompatibility complex class II-restricted T cells. It was
      found that they induce antigen-dependent lymphokine production by T cells and
      therefore could present exogenous antigens. These processing takes place
      intracellularly, because fixation abrogates presentation to T cells. Moreover,
      antigen presentation needs intracellular processing within endo- or lysosomes as
      chloroquine-treatment prevents T cell activation. Titration of APC numbers
      revealed that contaminating APC most likely did not account for antigen-specific
      T cell activation by DC. No evidence was found for release of antigenic peptides
      or for partial antigen processing possibly done by cell surface located enzymes
      on DC. In conclusion, these results indicate that freshly enriched DC are able to
      process antigens similarly to other APC.

PMID- 7805746
TI  - Identification of a naturally processed HLA A0201-restricted viral peptide from
      cells expressing human papillomavirus type 16 E6 oncoprotein.
AB  - Human papillomavirus (HPV) DNA encoding the oncogenic proteins E6 and E7 is
      usually retained in cervical carcinomas, implicating these proteins as potential
      target antigens for immune recognition in this virally associated tumor. We have
      characterized endogenously processed peptides eluted from major
      histocompatibility complex class I molecules in cells infected with a recombinant
      vaccinia expressing the HPV-16 E6 oncoprotein. The reverse-phase chromatography
      profile of peptides eluted from isolated HLA-A0201 molecules in cells expressing
      the E6 oncoprotein differs from that of cells not expressing E6. Sequential Edman
      degradation of novel peaks found in the peptide profiles from cells expressing
      HPV-16 E6 led to the identification of a naturally processed HLA-A0201-restricted
      E6 peptide of sequence KLPQLCTEL. This approach has allowed the identification of
      a viral peptide which is processed and presented by cells expressing the E6
      oncoprotein and is a likely target for cytotoxic T lymphocyte recognition in HLA
      A0201-positive patients.

PMID- 7805747
TI  - Identification of the core residues of the epitope of a monoclonal antibody
      raised against glycoprotein D of herpes simplex virus type 1 by screening of a
      random peptide library.
AB  - Random peptide libraries (RPL) displayed on the surface of a filamentous
      bacteriophage can be used to identify peptide ligands that interact with target
      molecules. We have used a 15-amino acid residue RPL displayed on bacteriophage
      M13 to identify the core residues within the epitope of a monoclonal antibody
      (mAb) A16 which interacts with a continuous epitope restricted to amino acid
      residues 9 to 19 in the N-terminal region of glycoprotein D of herpes simplex
      virus type 1 (gD-1). The single peptide sequence obtained after three rounds of
      selection contained identical residues at three positions compared to the
      authentic gD-1 sequence. Synthetic peptides were prepared based on the sequence
      of the original epitope and the phage-derived epitope. The binding constants (Ka)
      with mAb A16 were determined using surface plasmon resonance (SPR) biosensor
      technology. The RPL-derived peptide and peptide 9-19 of gD-1 had approximately
      the same affinity for mAb A16. This suggests that those residues within the
      epitope that are essential for binding were identified. The synthesis of shorter
      versions of the RPL-derived peptide restricted the binding region to seven amino
      acid residues. These results show that minimal information retrieved from the
      screening of an RPL combined with peptide synthesis can characterize the epitope
      of an mAb with high resolution. Immunization of mice with the phage-derived
      peptide protected against a challenge with a lethal dose of herpes simplex virus
      type 1 equally well as the gD-1 derived peptide.

PMID- 7805748
TI  - Induction by transforming growth factor-beta 1 of the interleukin-1 receptor
      antagonist and of its intracellular form in human polymorphonuclear cells.
AB  - The aim of this study was to examine the expression of interleukin-1 receptor
      antagonist (IL-1ra) in human polymorphonuclear cells (PMN) treated with
      transforming growth factor-beta 1 (TGF beta 1). TGF beta 1 induced IL-1ra
      transcripts in human circulating PMN and the induction was not blocked by protein
      synthesis inhibitors. Actinomycin D blocked induction by TGF beta 1 of IL-1ra
      transcripts, suggesting the involvement of gene transcription. The half life of
      IL-1ra transcripts was prolonged by TGF beta 1. By reverse transcriptase
      polymerase chain reaction, TGF beta 1 was found to augment the transcripts coding
      for both the intracellular (keratinocyte type) and the secreted form of IL-1ra.
      TGF beta 1 induced the production of IL-1ra in PMN. Induction of IL-1ra by TGF
      beta 1 in PMN may represent a further mechanism by which this molecule can
      counteract the potent pro-inflammatory properties of IL-1.

PMID- 7805749
TI  - Detachment and cytolysis of human endothelial cells by proteinase 3.
AB  - Activation and degranulation of polymorphonuclear leukocytes (PMN) with release
      of proteolytic enzymes, such as proteinase 3 (PR3) and elastase, in the vessels
      of patients with Wegener's granulomatosis (WG) is thought to play an important
      role in the vascular endothelial cell damage. We have investigated the detachment
      and cytolysis of 51Cr-labeled umbilical vein endothelial cells (HUVEC) induced by
      highly purified, enzymatically active, PR3 and elastase. Incubation of confluent
      monolayers of HUVEC with 100 mU/ml of PR3 for 3 h at 37 degrees C generally
      resulted in 20% detachment and 30% cytolysis. Elastase (350 mU/ml) induced
      approximately 40% detachment and 15% cytolysis. Both PR3-mediated and elastase
      mediated detachment and cytolysis were fully inhibited by alpha-1-proteinase
      inhibitor (alpha 1 PI), while anti-leukoprotease (ALP) only inhibited elastase
      mediated endothelial damage. By selective inhibition of an azurophilic granule
      extract with either alpha 1PI or ALP we calculated that PR3 is responsible for
      23% of the total detachment and cytolysis induced by the extract. Elastase was
      responsible for 60% of the detachment and 19% of the cytolysis. Detachment
      induced by PR3 was inhibited by three out of five IgG preparations purified from
      c-ANCA-positive sera of WG patients. PR3-mediated cytolysis was inhibited by each
      of the c-ANCA+IgG preparations and also to a limited extent by control IgG,
      suggesting a partial nonspecific stabilization of the endothelial cells. These
      studies provide evidence that besides elastase, PR3 also plays an important role
      in the PMN-mediated endothelial cell damage.

PMID- 7805750
TI  - Lymphocyte-activation gene 3/major histocompatibility complex class II
      interaction modulates the antigenic response of CD4+ T lymphocytes.
AB  - The activation requirements for antigen-dependent proliferation of CD4+ T cells
      are well documented, while the events leading to the inactivation phase are
      poorly understood. Here, we tested the hypothesis that the lymphocyte-activation
      gene 3 (LAG-3), a second major histocompatibility complex (MHC) class II ligand,
      plays a regulatory role in CD4+ T lymphocyte activation. CD4+ class II-restricted
      T cell clones were stimulated by their relevant antigen (hemagglutinin peptide or
      diphteria toxoid) and antigen-presenting cells with or without anti-LAG-3
      monoclonal antibody (mAb). Kinetic studies were performed to monitor different
      activation parameters, including the measurement of thymidine incorporation,
      expression of activation antigens and cytokine secretion. Results showed that the
      time course from the initial time points up to the peak time point was not
      modified in the presence of anti-LAG-3 mAb. However, addition of these
      antibodies, either as whole IgG or as Fab fragments, led to increased thymidine
      incorporation values for late time points and, hence, to a shift in the
      decreasing proliferation curve. We also showed that expression of activation
      antigens, such as CD25, was higher in the presence of anti-LAG-3 mAb, and that
      cytokine concentrations, i.e. of interferon-gamma or interleukin-4, were higher
      in the corresponding culture supernatants. In addition, we tested whether the
      effects of anti-LAG-3 mAb were limited to antigen-dependent, MHC class II
      restricted responses. The proliferative responses of CD4+ T cell clones following
      stimulation with either interleukin-2, mitogens, a combination of anti-CD2 mAb,
      immobilized anti-CD3 or anti-T cell receptor mAb were not altered by anti-LAG-3
      mAb. The allogeneic proliferative response of a CD8+ T cell clone was also not
      affected. Overall, the present analysis reveals a modulating effect of anti-LAG-3
      mAb, mediated specifically on antigen-dependent, MHC class II-restricted
      responses of CD4+ T cell lines. These results support the view that LAG-3/MHC
      class II interaction down-regulates antigen-dependent stimulation of CD4+ T
      lymphocytes.

PMID- 7805751
TI  - Interleukin-4 but not interleukin-10 inhibits the production of leukemia
      inhibitory factor by rheumatoid synovium and synoviocytes.
AB  - The expression of the proinflammatory cytokine leukemia inhibitory factor (LIF)
      has been reported in the cartilage and synovium of rheumatoid arthritis (RA)
      patients. Here, we show that high levels of LIF were constitutively produced by
      cultures of synovium pieces. Low levels of LIF were produced spontaneously by
      isolated synoviocytes, but interleukin (IL)-1 beta caused a fourfold enhancement
      of this secretion. The anti-inflammatory cytokine IL-4 reduced the production of
      LIF by synovium pieces by 75%, as observed earlier with IL-6, IL-1 beta and tumor
      necrosis factor (TNF)-alpha. IL-4 had a direct effect since it inhibited LIF
      production by unstimulated and IL-1 beta- or TNF-alpha-stimulated synoviocytes.
      Conversely, IL-4 enhanced the production of IL-6, which shares with LIF
      biological activities and receptor components. The inhibitory effect of IL-4 was
      dose dependent and was reversed using a blocking anti-IL-4 receptor antibody.
      Similar inhibitory action of IL-4 on LIF production was observed on synovium
      pieces from patients with osteoarthritis and on normal synoviocytes. IL-10,
      another anti-inflammatory cytokine acting on monocytes, had no effect on LIF
      production by either synovium pieces or isolated synoviocytes. Thus, the
      production of LIF by synovium tissue was inhibited by IL-4 through both a direct
      effect on synoviocytes and an indirect effect by inhibition of the production of
      LIF-inducing cytokines.

PMID- 7805752
TI  - Induction of natural killer cell migration by monocyte chemotactic protein-1, -2
      and -3.
AB  - Under certain physiological and pathological conditions, natural killer (NK)
      cells rapidly accumulate in tissues. Chemokines are an essential component of the
      current paradigm of leukocyte recruitment. The present study was designed to
      investigate the responsiveness of NK cells to the prototypic C-C chemokine,
      monocyte chemotactic protein-1 (MCP-1). MCP-1 induced migration across filters of
      interleukin (IL)-2-activated NK cells, whereas it was a weak attractant for
      unstimulated cells. Maximal induction of migration required a positive
      concentration gradient between the lower and the upper compartment of the
      chemotaxis chamber. Preliminary characterization of the MCP-1 receptor on NK
      cells indicated that the chemotactic response to MCP-1 was blocked by pre
      treatment of cells with Bordetella pertussis toxin, and MCP-1 but not IL-8
      displaced 125I-labeled MCP-1 from IL-2-activated NK cells. The related chemokines
      MCP-2 and MCP-3 were also active--though less potent--attractants for activated
      NK cells. Thus the spectrum of action of MCP-1, -2 and -3 encompasses NK cells
      and chemokines are likely to play a role in regulating extravasation of these
      cells.

PMID- 7805753
TI  - Interleukin-8 differentially modulates interleukin-4- and interleukin-2-induced
      human B cell growth.
AB  - The effect of interleukin-8 (IL)-8 on human B cell growth, as determined by
      thymidine uptake and viable cell numbers was studied. IL-8 inhibited IL-4-induced
      growth of B cells costimulated with anti-mu antibodies (Ab) or Staphylococcus
      aureus Cowan strain I (SAC) in a dose-dependent fashion. In contrast, IL-8 did
      not inhibit IL-2-induced growth of B cells. The IL-8-mediated inhibition was
      specific, since it was blocked by anti-IL-8 mAb but not by control IgG1.
      Moreover, anti-tumor necrosis factor-alpha (anti-TNF-alpha) Ab blocked IL-8
      mediated inhibition. On the other hand, TNF-alpha, but not other cytokines
      including IL-1 beta, IL-3, IL-5, IL-6, interferon-alpha (IFN-alpha) or IFN-gamma,
      inhibited IL-4-mediated growth, and inhibition by TNF-alpha was blocked by anti
      TNF-alpha Ab but not by control IgG. IL-4 had no effect on TNF-alpha binding by B
      cells while it decreased TNF-alpha production by B cells. IL-8 had no effect in
      binding of IL-4, IL-2 or TNF-alpha by B cells, however, it enhanced TNF-alpha
      production by B cells. These results indicate that IL-8 inhibited IL-4-induced
      human B cell growth by enhancement of endogenous TNF-alpha production.

PMID- 7805755
TI  - Neuropeptide Y promotes GTP photo-incorporation into a 55 kDa protein.
AB  - Incubation of bovine hippocampal membranes with [alpha-32P]GTP and exposure to
      ultraviolet light resulted in the labelling of seven species with apparent
      molecular masses of 200, 74, 55, 53, 50, 43 and 40 kDa. Labelling of the 55 kDa
      species was greatly enhanced in the presence of carboxyl terminal fragments
      [neuropeptide Y-(18-36)] of neuropeptide Y. Labelling occurred with [alpha
      32P]GTP but not [alpha-32P]ATP. A group of putative direct G protein activating
      peptides including mastoparan, melittin, substance P and adrenocorticotropic
      hormone (ACTH)-(1-24), were also able to stimulate the labelling of this protein.
      Labelling of the 55 kDa protein could be demonstrated in bovine brain but not
      peripheral tissues. Western blot analysis using an antibody against the common
      alpha subunit of G proteins recognized a protein co-migrating with the 55 kDa GTP
      binding protein. These findings demonstrate the existence of a previously
      uncharacterized neuronal protein, with an apparent molecular mass of 55 kDa, that
      binds GTP in response to neuropeptide Y and other peptides.

PMID- 7805756
TI  - Vanadate-induced oscillatory inward Cl- currents in Xenopus laevis oocytes.
AB  - Extracellularly applied sodium orthovanadate (30-3000 microM) evoked oscillatory
      inward Cl- currents in defolliculated Xenopus laevis oocytes. The current
      responses were attenuated by microinjection of EGTA into the oocytes and by
      treatment of the oocytes with pertussis toxin (2 micrograms/ml). The vanadate
      responses were not affected by preceding vanadate (1 mM) responses or an
      angiotensin II (200 nM) response, or by pre-application of atropine (5 microM).
      Intracellular injection of vanadate was ineffective. These results suggest that
      vanadate stimulates Ca2+ mobilization in Xenopus oocytes possibly by activating
      surface membrane receptors, which is coupled to pertussis toxin-sensitive G
      protein.

PMID- 7805757
TI  - Modulation of dihydropyridine receptors in vascular smooth muscle cells by
      membrane potential and cell proliferation.
AB  - We have studied binding of isradipine to A7r5 vascular smooth muscle cells as a
      function of membrane potential and cell proliferation. Consistent with a voltage
      modulated receptor model, two classes of binding sites were detected in confluent
      cultures: high-affinity sites under depolarizing (50 mM K+) conditions (Kd = 45
      +/- 3 pM), and lower affinity sites under resting (5 mM K+) conditions (Kd = 181
      +/- 20 pM). However, proliferating cells also displayed the high-affinity state
      at rest (Kd = 29 +/- 9 pM) in addition to a low-affinity site (Kd = 869 +/- 383
      pM). Analysis of dissociation rates also revealed two receptor classes during
      proliferation. Proliferating cells showed a single class of high-affinity sites
      (Kd = 39 +/- 6 pM) when depolarized, similar to confluent cells. Receptor density
      in confluent monolayers increased from 15 +/- 3 fmol/10(6) cells at 5 days to 72
      +/- 6 fmol/10(6) cells after 10 days. These results suggest (i) that some L-type
      Ca2+ channels are spontaneously active in proliferating vascular smooth muscle
      cells, but require depolarization to activate in a confluent monolayer, and (ii)
      that the density of dihydropyridine receptors increases after a monolayer becomes
      confluent.

PMID- 7805754
TI  - T cell receptor and peptide-contacting residues in the HLA-DR17(3) beta 1 chain.
AB  - Previously, we have proposed that the beta 1 residues 9-13, 26, 28 and 86 in HLA
      DR17, the most common subtype of DR3, might be critical for the binding of an
      immunodominant, mycobacterial epitope (peptide 3-13 of the 65-kDa heat shock
      protein). In order to examine directly (i) which DR17 residues are involved in
      peptide binding, (ii) whether the same or other DR17 residues are involved in the
      binding of different peptides, and (iii) whether subtle differences in the mode
      of peptide binding can influence T cell stimulation, we have now systematically
      mutated 15 highly polymorphic DR17 beta 1 residues, located in the proposed
      peptide binding groove of DR17, and examined the effect thereof on binding and
      presentation of two peptides, hsp65 p3-13 and p56-65 of the 30/31-kDa secreted
      mycobacterial protein. Mutations in residues 28 (D-->H) and 86 (V-->G) completely
      eliminated binding of p3-13 and significantly reduced binding of p56-65. A
      mutation in residue 26 (Y-->F) decreased binding of p3-13 but did not affect
      binding of p56-65. Substitutions of amino acid residues 28, 67, 71 and 86 in the
      DR17 beta 1 chain abrogated peptide-specific stimulation of both the p3-13- and
      the p56-65-specific T cell clones, while specific stimulation by only one peptide
      was eliminated by substitution at positions 26 and 74 (p3-13) and by substitution
      of residues 11 and 37 (p56-65). The observation that substitution of several
      other peptide-contacting DR17 beta 1 chain residues does not significantly affect
      peptide binding but does affect T cell stimulation, suggests that these
      substitutions alter the conformation of the bound peptide.

PMID- 7805758
TI  - Enhanced excision repair of DNA damage due to cis-diamminedichloroplatinum(II) in
      resistant cervix carcinoma HeLa cells.
AB  - We have previously reported a cisplatin-resistant HeLa cell line which exhibits
      overproduction of nuclear proteins preferential for cisplatin-modified DNA (Chao
      et al., Cancer Res. 51:601-605, 1991; Biochem. J. 277: 875-878, 1991). In this
      study, excision repair of cisplatin-DNA adducts in a resistant and a revertant
      cell lines was investigated using in situ detection of cisplatin-DNA adducts by
      an immunoassay and the measurement of repair-associated DNA strand breaks by a
      sensitive alkaline elution method. The resistant cells exhibited a 2-fold
      decrease in the accumulation of cisplatin-DNA adducts; whereas, the revertant
      cells showed a similar level of cisplatin-DNA adducts as the parental cells in
      the parallel experiment. Immediately following cisplatin treatment, the resistant
      and the revertant cells accumulated respectively approximately 50% and 90%
      cisplatin-DNA adducts of the parental cells. However, the kinetic patterns of
      repair rate following peak accumulation of cisplatin-DNA adducts (which took
      approximately 4 h) was the same in the three cell lines. This finding was
      supported by the measurement of repair-associated DNA strand breaks using
      alkaline elution which showed 1.6- and 1.5-fold increase in the resistant and the
      revertant cells respectively. In addition, following transfection with plasmid
      DNA carrying cisplatin damage, the resistant and the revertant cells displayed a
      2.4- and 1.4-fold enhancement in host cell reactivation, respectively.
      Furthermore, the acquired resistance in HeLa cells was partially reversed by
      nontoxic aphidicolin, a DNA polymerase-alpha and DNA repair inhibitor. The
      results strongly suggest the improved excision repair of cisplatin-DNA adducts as
      a mechanism of phenotypic resistance of cells to cisplatin.

PMID- 7805759
TI  - Thermodynamics of the binding of BTCP (GK 13) and related derivatives on the
      dopamine neuronal carrier.
AB  - We have studied the thermodynamic properties of the binding of a coherent series
      of uptake inhibitors derived from BTCP (GK 13 = N-[1-(2
      benzo(b)thiophenyl)cyclohexyl]piperidine) to the dopamine neuronal carrier
      labelled with [3H]GBR 12783 (1-[2-(diphenylmethoxy)ethyl]4-(3-phenyl-2-propenyl)
      piperazine). GK 13 (30 nM) and its 2-naphthyl derivative GK 189 (15 nM)
      competitively inhibited the specific binding of [3H]GBR 12783 to sites present in
      rat striatal membranes. Hill numbers calculated for the inhibition of the
      specific binding of [3H]GBR 12783 by BTCP derivatives were close to 1 (range 0.79
      1.18). Increasing the temperature from 0 degrees to 30 degrees C induced a
      decrease in the affinity of [3H]GBR 12783 and GK derivatives which was generally
      less pronounced than that obtained when temperature was raised from 30 degrees C
      to 37 degrees C. Increasing the incubation temperature led to a decrease in both
      enthalpy (delta H degrees) and entropy (delta S degrees). We observed at 37
      degrees C a large negative enthalpy change (range -48, -79 kJ/mol) and a
      negative, binding unfavorable, change in entropy. This indicates that the GK
      derivatives binding is enthalpy-driven. Furthermore, data obtained in the present
      study show that changes in thermodynamic parameters are not a function of the
      inhibitor's affinity for the dopamine neuronal carrier and this suggests that
      bonds involved in the inhibitor-carrier interaction are more likely related to
      the carrier configuration than to the chemical structure of the inhibitor.

PMID- 7805760
TI  - Ryanodine and an iodinated analog: doxorubicin effects on binding and Ca2+
      accumulation in cardiac sarcoplasmic reticulum.
AB  - An 125I-iodinated ryanodine analog, modified by attaching an iodo-Cbz-beta-alanyl
      group to the C10eq hydroxy of ryanodine (iodo-carbobenzyloxy-beta-alanyl
      ryanodine), binds to cardiac sarcoplasmic reticulum Ca2+ release channels with
      equal affinity as [3H]ryanodine. In the present study, both iodo-Cbz-beta-alanyl
      ryanodine and ryanodine bound to canine cardiac microsomal membrane preparations
      in a Ca2+ dependent manner. At 10 microM free Ca2+ doxorubicin increased specific
      binding of both ligands, with doxorubicin concentrations of 4.06 +/- 0.44 and
      6.22 +/- 1.31 microM inducing 50% maximal enhancement of binding for ryanodine
      and iodo-Cbz-beta-alanyl-ryanodine, respectively. Effects of ryanodine and iodo
      Cbz-beta-alanyl-ryanodine +/- doxorubicin in vitro on cardiac sarcoplasmic
      reticulum Ca2+ release were compared indirectly by determining Ca2+ accumulation
      in cardiac microsomal vesicles loaded with 45Ca2+. In the absence of oxalate,
      neither ryanodine nor iodo-Cbz-beta-alanyl-ryanodine (10 microM) decreased net
      Ca2+ uptake, whereas doxorubicin reduced Ca2+ accumulation 20 +/- 2%. In the
      presence of oxalate and 0.4 microM free Ca2+ ("low"), both ryanodine and iodo-Cbz
      beta-alanyl-ryanodine modestly decreased (by 19% and 17% at 10 nM, respectively)
      maximum Ca2+ accumulation. Increasing concentrations of ryanodine (100 nM-100
      microM) and iodo-Cbz-beta-alanyl-ryanodine (100 nM-30 microM) had no greater
      effect, but 100 microM iodo-Cbz-beta-alanyl- ryanodine decreased net Ca2+ uptake
      57 +/- 3%. Doxorubicin (30 microM) alone reduced Ca2+ uptake 36%; its effects
      with 1 nM-10 microM ryanodine or 1 nM-100 microM iodo-Cbz-beta-alanyl-ryanodine
      were additive.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7805761
TI  - Potentiation by insulin and insulin-like growth factor-1 of glibenclamide
      sensitive K+ currents in follicle-enclosed Xenopus oocytes.
AB  - Effects of insulin and IGF-1 (insulin-like growth factor-1) on K+ channel opener
      induced/glibenclamide-sensitive K+ currents were studied using follicle-enclosed
      Xenopus oocytes. Both insulin (4 x 10(-9)-4 x 10(-6) M) and IGF-1 (4 x 10(-10)-4
      x 10(-7) M) increased the cromakalim-induced K+ currents in a concentration
      dependent manner. The current-facilitating effect of IGF-1 was about ten times as
      potent as that of insulin. Treatment of the oocyte with pertussis toxin (2
      micrograms/ml) suppressed the current-potentiating effects of insulin and IGF-1
      by about 60%. Although phenylarsine oxide (1-100 microM), a putative inhibitor of
      protein tyrosine phosphatase, also facilitated the K+ currents, the current
      enhancing effects were not affected by pertussis toxin. These results suggest
      that insulin and IGF-1 potentiate the glibenclamide-sensitive K+ current by
      activating IGF-1 receptor and that pertussis toxin-sensitive G-protein may be
      associated with these effects.

PMID- 7805763
TI  - Identification of the alpha 1c-adrenoceptor in rabbit arteries and the human
      saphenous vein using the polymerase chain reaction.
AB  - The expression of the alpha 1C-adrenoceptor subtype in human and rabbit blood
      vessels has been analyzed using the reverse transcriptase/polymerase chain
      reaction technique (RT/PCR). The 20 bp primers employed were designed from the
      bovine alpha 1C-adrenoceptor and flank a least conserved region--the putative
      third cytoplasmic loop. RT/PCR products generated from rabbit and human brain
      mRNA both had 93% homology to the bovine alpha 1C-adrenoceptor and were used as
      species and subtype specific probes in Southern blot analysis of vascular RT/PCR
      products. Poly A+ RNA was purified from the human saphenous vein and rabbit
      aorta, renal, pulmonary and central ear arteries and amplified by RT/PCR. Size
      analysis by agarose gel electrophoresis, together with Southern hybridization of
      the resulting cDNA products confirm the expression of the alpha 1C-adrenoceptor
      in these vessels.

PMID- 7805762
TI  - Down-regulation and desensitization of the muscarinic M1 and M2 receptors in
      transfected fibroblast B82 cells.
AB  - Murine fibroblast cell lines stably transfected with the rat muscarinic m1 or m2
      receptor genes were used to study the homologous regulation of the muscarinic M1
      or M2 receptors. The cells were pretreated with the muscarinic receptor agonists,
      (+)-cismethyl-dioxolane, carbachol, 2,8-dimethyl-3-methylene-1-oxa-8-aza-spiro-
      [4,5]decane ((+) or (-)-YM796) or the muscarinic receptor antagonist atropine for
      up to 24 h. Our study has demonstrated that the muscarinic receptor nonselective
      full agonist, (+)-cismethyl-dioxolane, induced the down-regulation of both the
      muscarinic M1 and the M2 receptors in association with desensitization of the
      receptor-mediated functions. The muscarinic M1 receptors are down-regulated
      without significant receptor internalization while the muscarinic M2 receptors
      are more sensitive to down-regulation than the muscarinic M1 receptors because of
      significant internalization of the muscarinic M2 receptors in our system. The
      muscarinic M1 receptor partial agonist, (-)-YM796 induced less down-regulation
      and no significant desensitization of the muscarinic M1 receptors with no
      substantial effect on the muscarinic M2 receptor density or function.

PMID- 7805764
TI  - The pharmacological profile of cloned and stably expressed alpha 1b-adrenoceptor
      in CHO cells.
AB  - Using Chinese hamster ovary (CHO) cells stably expressing the alpha 1B
      adrenoceptor (CHO alpha 1B cells) as a model, we investigated whether the
      transfected cells that express alpha 1B subtype of adrenoceptor can show the
      pharmacologic characteristics as previously defined in native tissues.
      Radioligand binding studies with 2-[beta-(4-hydroxy-3-[125I]iodophenyl)ethylamino
      methyl]tetralone ([125I]HEAT) in CHO alpha 1B cells showed the similar Ki values
      of the alpha 1-adrenoceptor selective drugs as previously observed in rat liver
      and spleen, and that pretreatment with chlorethylclonidine markedly inactivated
      the binding sites (94.7-98.6%). In CHO alpha 1B cells alpha 1-adrenoceptor
      agonists caused a dose-dependent increase in transients of cytosolic Ca2+
      concentrations ([Ca2+]i), and the potency order of antagonists in inhibiting
      norepinephrine-induced [Ca2+]i response was similar to that observed in
      radioligand binding assays. In summary, the present study shows that the ligand
      binding property, the pharmacological characteristics and the intracellular
      transduction mechanisms of alpha 1B-adrenoceptors stably expressed in CHO cells
      appear to be the same as those defined in native tissues. Thus they can be a
      useful model system for further characterization of the receptor as well as for
      the development of specific ligands.

PMID- 7805765
TI  - Evidence for an NMDA receptor subunit in human keratinocytes and rat cardiocytes.
AB  - Receptor binding studies have demonstrated the presence of an [3H]MK-801 ([3H](+)
      5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-im ine maleate) binding
      site in human keratinocytes. The affinity found in keratinocytes was lower than
      that found in brain membranes. Northern blots identified mRNA in human
      keratinocytes and rat cardiocytes, as well as rat brain, that hybridized with
      high stringency to a probe for NMDAR1, an NMDA receptor subunit. In each tissue,
      mRNA that hybridized to another glutamate binding protein that might be part of
      an NMDA receptor complex, was also present. The presence of NMDA or NMDA-like
      receptors in keratinocytes and rat cardiocytes together with the low affinity
      [3H]MK-801 binding suggests that this protein may be a general channel forming
      protein that is present in many tissues, and forms specific receptors by
      interacting with additional subunits.

PMID- 7805766
TI  - Nimesulide decreases superoxide production by inhibiting phosphodiesterase type
      IV.
AB  - Nimesulide, the prototype of a new class of anti-inflammatory drugs, dose
      dependently decreases the production of the superoxide anion (O2-.) in N-formyl
      methionyl-leucyl-phenylalanine (fMLP)- and in phorbol myristate acetate (PMA)
      stimulated polymorphonuclear leukocytes. The inhibition of O2-. is possibly
      related to its inhibitory effect on polymorphonuclear leukocyte cytosolic
      phosphodiesterase type IV (IC50 = 39 +/- 2 microM), to the related increase in
      cAMP (P < 0.01 at 1 microM) and the subsequent increase in protein kinase A
      activity. In fact H-89, a specific protein kinase A inhibitor, counteracts the
      inhibitory effect of nimesulide on O2-. production by fMLP and PMA. The
      activation of protein kinase A may prompt the phosphorylation of a number of
      substrates, thus inhibiting the assembly of NADPH-oxidase in the plasma membrane.
      Accordingly, nimesulide decreases PMA-induced assembly of NADPH-oxidase in
      polymorphonuclear leukocytes plasma membranes by about 35%. Protein kinase A
      activation may also interfere with chemotaxis. Nimesulide inhibits stimulated
      chemotaxis and the effect is decreased by H-89. Inhibition of phosphodiesterase
      type IV may explain many of nimesulide's effects.

PMID- 7805767
TI  - 5-HT1D receptor type is involved in stimulation of cell proliferation by
      serotonin in human small cell lung carcinoma.
AB  - Serotonin (5-hydroxytryptamine, 5-HT), a neurotransmitter and vasoactive agent,
      is contained in two small cell lung carcinoma cell lines GLC8 and NCI-N-592 and
      is released in the culture medium. It also stimulates DNA synthesis in the same
      cell lines. In GLC8 cells this mitogenic effect is not counteracted by
      ketanserin, ICS 205-930 and GR 113-808 which are antagonists of the 5-HT2, 5-HT3
      and 5-HT4 receptors, respectively. On the contrary, the antagonists metergoline,
      methysergide, SDZ 21-009 and methiothepin inhibit the 5-HT-stimulated
      incorporation of [3H]thymidine in GLC8 cells. The 5-HT1D agonist sumatriptan is
      capable of mimicking 5-HT action on cell proliferation. Both sumatriptan and 5-HT
      inhibit adenylate cyclase activity at doses which correlate with the mitogenic
      effect. We conclude that a 5-HT1D receptor type contributes to the mitogenic
      effect of 5-HT in GLC8 cells. This is the first demonstration of an involvement
      of the 5-HT1D receptor type in human cell proliferation. The design of specific
      antagonists for this type of receptor might be useful for the growth control of
      this very aggressive tumor.

PMID- 7805768
TI  - The phospholipase C activating P2U purinoceptor also inhibits cyclicAMP formation
      in DDT1 MF-2 smooth muscle cells.
AB  - The P2U purinoceptor mediated effect on cellular cAMP was investigated in DDT1 MF
      2 smooth muscle cells. Stimulation of these receptors by ATP or UTP caused a
      pronounced decrease of about 50% in cellular cAMP levels in forskolin or
      isoprenaline pretreated cells. This action of the nucleotides was concentration
      dependent with an IC50 of 9.4 +/- 0.2 microM and 29.0 +/- 0.5 microM for UTP and
      ATP, respectively and was inhibited by the P2-purinoceptor antagonist suramin.
      The cAMP level appeared to be modified by intracellular Ca2+, represented by an
      initial decline in cAMP. Neither inactivation of protein kinase C by
      staurosporine nor elevated cytoplasmic Ca2+ concentrations interfered with the
      sustained decrease in cAMP levels induced by ATP or UTP, showing that this effect
      is not mediated via the phospholipase C pathway known to be activated after P2U
      purinoceptor stimulation in DDT1 MF-2 cells. Pertussis toxin inhibited the action
      of these nucleotides on the cellular cAMP level. It can be concluded that the P2U
      purinoceptor in DDT1 MF-2 cells is coupled to different G-proteins, activating
      phospholipase C and inhibiting adenylyl cyclase activity.

PMID- 7805769
TI  - Chronic D-fenfluramine decreases serotonin transporter messenger RNA expression
      in dorsal raphe nucleus.
AB  - In situ hybridization was used to measure the effects of chronic fenfluramine
      administration on serotonin transporter messenger RNA expression in cells of the
      dorsal raphe nucleus complex. Fenfluramine produced a significant, but transient,
      down-regulation of serotonin transporter mRNA in cells which lie in the ventral
      portion of the dorsal raphe nucleus, but not in the dorsal part of the dorsal
      raphe nucleus. Our findings suggest that cells which lie in the ventral part of
      the dorsal raphe nucleus are more sensitive to the effects of chronic
      fenfluramine administration, but that fenfluramine does not cause long-term
      changes in gene expression in serotonin cell bodies.

PMID- 7805770
TI  - Functional evidence for an apical ANP receptor in LLC-PK1 kidney epithelial
      cells.
AB  - The localization of natriuretic peptide receptors was studied in LLC-PK1 cell
      monolayers grown on a micro-porous membrane filter. The addition of alpha-human
      atrial natriuretic peptide (alpha-hANP) to the apical side of the cells produced
      a concentration-dependent increase in cyclic GMP (cGMP) formation, the extent of
      which was similar to that produced by the addition to the basolateral side. More
      cGMP was formed with alpha-hANP (1 and 100 nM) than with the C-type natriuretic
      peptide (100 nM). These findings indicate that the biologically active receptors
      with high efficacy for alpha-hANP are expressed in both the apical and
      basolateral membranes in LLC-PK1 cells.

PMID- 7805771
TI  - Characterisation of mu-opioid receptors on SH-SY5Y cells using naloxonazine and
      beta-funaltrexamine.
AB  - The irreversible opioid receptor antagonists naloxonazine and beta-funaltrexamine
      have been used to determine whether multiple mu-opioid receptors exist on
      undifferentiated SH-SY5Y human neuroblastoma cells. Naloxonazine binds
      irreversibly to the mu 1-opioid receptor subtype and reversibly to the mu 2
      opioid receptor subtype. On SH-SY5Y cells naloxonazine afforded a Ki of 3.4 +/-
      0.7 nM, and was fully reversible, indicating the mu-opioid receptor population on
      SH-SY5Y cells was solely of the mu 2-opioid receptor subtype. The alkylating
      agent beta-funaltrexamine was maximally able to alkylate only 60% of the mu
      opioid receptor sites on SH-SY5Y cells, labelled with [3H]diprenorphine or [3H][D
      Ala2,MePhe4,Gly(ol)5]enkephalin (DAMGO). The reversible binding of naloxonazine
      and the insensitivity of a percentage of the mu-opioid receptor sites to
      alkylation by beta-funaltrexamine suggests that differences do exist in the mu 2
      opioid receptor population on undifferentiated SH-SY5Y cells. This may indicate
      further heterogeneity or the inability of beta-funaltrexamine to alkylate all
      relevant nucleophilic groups in a single population of receptors.

PMID- 7805772
TI  - Receptor-mediated modulation of rat KV1.2 in Xenopus oocytes.
AB  - To investigate mechanisms for the receptor-mediated inhibition of a rat cardiac
      K+ channel clone (KV1.2), we coexpressed KV1.2 with a subtype of endothelin
      receptors (ETA) in Xenopus oocytes. Effects of endothelin ETA receptor
      stimulation were mimicked by application of PMA (4-beta-phorbol 12-myristate 13
      acetate; 0.1 microM) or intracellular injection of CaCl2 (estimated concentration
      of 1 microM). These effects diminished in the presence of staurosporine (1
      microM) or EGTA (estimated concentration of 5 mM). These results suggest that
      both activation of protein kinase C and an increase in intracellular Ca2+
      contribute to the suppression.

PMID- 7805773
TI  - FCCP modulation of Ca2+ oscillation in rat megakaryocytes.
AB  - The effects of a mitochondrial uncoupler, FCCP, (carbonyl cyanide-p
      trifluromethoxyphenyl-hydrazone) on the regulation of cytoplasmic Ca2+ were
      investigated in ATP-induced Ca2+ oscillation system of rat megakaryocyte.
      Application of FCCP did not induce any detectable Ca(2+)-activated K+ current
      (IKCa) but pretreatment with FCCP modulated the ATP-induced repetitive IKCa. FCCP
      abolished the IKCa induced by low concentrations of ATP. However, when the
      concentration of ATP was high, the uncoupler also changed the periodic current to
      a sustained one. Similar biphasic regulation by the uncoupler was observed in the
      case of IP3-evoked repetitive IKCa. These results indicate that FCCP inhibits
      both Ca2+ mobilization and elimination processes after IP3 liberation induced by
      agonist stimulation.

PMID- 7805775
TI  - Ethanol causes decrements in airway excretion of endogenous nitric oxide in
      humans.
AB  - Ethanol has previously been demonstrated to inhibit excretion of endogenous
      nitric oxide (NO) in exhaled air from experimental animals. The aim of the
      present study was to elucidate if this effect also occurs in human subjects.
      Healthy volunteers ingested ethanol (0.25 and 1 g kg-1, 20% in orange juice).
      Nitric oxide in exhaled air was determined by chemiluminescence. Single-breath
      analysis of exhaled air was performed and peak values of NO and end expiratory
      levels of NO and CO2 were determined. Ethanol induced dose-dependent decrements
      in exhaled nitric oxide. Thus, peak values for nitric oxide in exhaled air, in
      the first exhalation after breath-holding for 30 s, decreased to 56 +/- 10 and 37
      +/- 12% of control 60 min after ingestion of ethanol at 0.25 and 1 g kg-1,
      respectively. Rinsing the oral cavity (including gargling) for 15 min with 20%
      ethanol in juice did not significantly influence NO in exhaled air. Heart rate
      blood pressure and end expiratory levels of CO2 were not significantly affected
      by ethanol ingestion. In conclusion, ethanol decreases levels of nitric oxide in
      exhaled air in humans, likely by inhibition of airway formation of nitric oxide.
      The results might be of importance in understanding effects of ethanol and other
      hydrocarbons.

PMID- 7805774
TI  - Binding profile of the selective muscarinic receptor antagonist tripitramine.
AB  - The binding selectivity of the muscarinic antagonist tripitramine has been tested
      on the five cloned human muscarinic receptor subtypes (Hm1 to Hm5) expressed in
      chinese hamster ovary (CHO-K1) cells. The results indicate that tripitramine
      binds to the muscarinic Hm2 receptor with a Ki value of 0.27 +/- 0.02 nM.
      Tripitramine distinguishes Hm2 vs. Hm4 by a factor of 24 and vs. Hm3 and Hm5 by a
      factor of 142 and 125, respectively. A lower affinity ratio, about 6-fold, was
      found between muscarinic Hm2 and Hm1 receptors. A comparative study with the well
      known selective muscarinic M2 receptor antagonist methoctramine indicates that
      tripitramine has gained both potency and selectivity for the muscarinic Hm2
      receptor subtype.

PMID- 7805776
TI  - Effect of 2,3,7,8-tetrachlorodibenzoy-p-dioxin on the hepatic 7-ethoxyresorufin O
      deethylase activity in four rodent species.
AB  - Temporal and dose-related effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
      on hepatic 7-ethoxyresorufin O-deethylase (EROD) activity were investigated in
      young male Hartley guinea pigs, Sprague-Dawley rats, C57Bl/6 mice, DBA/2 mice and
      Golden Syrian hamsters. Animals were terminated 1, 7, 14, 28, 56 and 112 days
      after the administration of a single i.p. dose of TCDD. The maximal induction of
      EROD activity, at doses producing a similar toxic and limited lethal effect in
      all species/strains, was 42-, 18-, 7- and 3-fold in rats, DBA/2 mice, C57Bl/6
      mice and guinea pigs, respectively. No treatment-related induction of EROD
      activity was observed in hamsters. Generally, maximal induction occurred 1-4
      weeks after injection in all species. The guinea pig alone maintained the same
      magnitude of induction of EROD activity throughout the study. Observed toxic
      effects, i.e., lethality, loss of body weight gain, liver enlargement and thymic
      atrophy, did not correlate with the TCDD-induced hepatic EROD activity. The
      obtained results suggest that the fold induction of cytochrome P450 1A1 activity
      is not a critical event for the expression of the lethal effect of TCDD in
      rodents.

PMID- 7805777
TI  - Immunomodulatory effect of sodium dodecyl sulfate on human neutrophils and the
      human promyelocytic HL-60 cell line.
AB  - The effect of sodium dodecyl sulfate (SDS), an anionic amphiphilic detergent, on
      the function of human neutrophils and of the human promyelocytic leukemia cell
      line HL-60 was investigated. SDS modulated the respiratory burst in human
      neutrophils and HL-60 cells which were stimulated with phorbol 12-myristate 13
      acetate (PMA). In concentrations above 1 X 10(-6) M it also caused release of
      lysosomal enzymes (beta-D-glucuronidase, myeloperoxidase and lysozyme) from
      neutrophils. Our results demonstrate that SDS at concentrations 1 X 10(-6) M-1 X
      10(-4) M strongly affect properties of human phagocytic cells.

PMID- 7805778
TI  - Effect of 3'-hydroxyfarrerol on airway hyperreactivity induced by acute cigarette
      smoke exposure in guinea pigs.
AB  - The (+/-)-3'-hydroxyfarrerol (IdB 1031) is a new drug endowed with an interesting
      mucokinetic activity. In this study the effectiveness of IdB 1031 has been
      verified in a model of airway hyperreactivity and lung inflammation induced in
      anaesthetized guinea pig by active cigarette smoke exposure. IdB 1031 (500 mg/kg
      per os) completely inhibited the capacity of cigarette smoke to induce airway
      hyperreactivity. IdB 1031 also inhibited the recruitment of proinflammatory cells
      within the airway lumen as showed in bronchoalveolar lavage fluids. In line with
      these experiments IdB 1031 inhibited 5-lipoxygenase with an IC50 of 7.36 x 10(-6)
      M in human leukocytes challenged by A-23187 (2 microM). A significant reduction
      of the above parameters was observed also in animals exposed to smoke after
      repeated treatment with IdB 1031 at 200 mg/kg per os for 15 days. These results
      show that IdB 1031 is a promising drug with a favourable spectrum of activities
      on the respiratory tract.

PMID- 7805779
TI  - Glibenclamide inhibits hypoxic relaxation of isolated porcine coronary arteries
      under conditions of impaired glycolysis.
AB  - The possible involvement of ATP-sensitive K+ channels (KATP) in hypoxic
      relaxation of isolated porcine coronary arteries was investigated. Tubular
      segments taken from the left anterior descending artery were suspended in
      myographs for recording of isometric contractile force. Hypoxia (pO2 = 20.3 mm Hg
      +/- 0.5) produced a greater relaxation in preparations contracted by 30 mM K+
      (49.7% +/- 7.2) compared with 124 mM K+ (19.9% +/- 2.2) which is compatible with
      the involvement of K+ channel activation in the mechanism of hypoxic relaxation.
      In a normal glucose-containing Krebs solution the KATP blocker glibenclamide (1
      microM) failed to influence the hypoxic relaxation of preparations contracted by
      the thromboxane A2 analogue U-46619. Under conditions created to inhibit non
      oxidative ATP production from glycolysis using a glucose-free Krebs solution
      containing 2-deoxyglucose (10 mM), the hypoxic relaxation was enhanced from 54.5%
      +/- 5.0 to 77.2% +/- 4.4. Under these conditions glibenclamide (1 microM)
      significantly inhibited the hypoxic relaxant response from 77.2% +/- 4.2 to 55.2%
      +/- 4.4 and prolonged the time until half-maximal relaxation from 5.5 min +/- 0.6
      to 8.1 min +/- 0.6. A low concentration of the KATP opener levcromakalim (30 nM)
      failed to significantly potentiate the hypoxic relaxation. The adenosine receptor
      blocker theophylline (1 microM) or removal of the endothelium showed no effect on
      the hypoxic relaxation. In normal glucose-containing Krebs solution, indomethacin
      (10 microM) caused a small but significant inhibition of the hypoxic relaxation
      from 54.5% +/- 5.0 to 41.6% +/- 3.6.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7805780
TI  - Effect of hypoxia on contraction and 45Ca2+ uptake induced by the thromboxane
      mimetic U46619 in sheep coronary artery.
AB  - The thromboxane mimetic U46619 (11 alpha,9 alpha-epoxymethano PGH2) increased
      45Ca2+ uptake in sheep coronary artery rings. A larger increase occurred in
      endothelium-denuded than in endothelium-inact rings (increase in 45Ca2+ uptake:
      endothelium intact = 9.6 +/- 3.8, endothelium-denuded = 33.2 +/- 8.1 nmol g-1),
      in agreement with the increase in U46619 contraction produced by endothelium
      denudation. Hypoxia (PO2 = 4 mm Hg) inhibited both the U46619 contraction (at the
      U46619 EC50, contraction under oxygenated conditions = 158 +/- 35, under hypoxic
      conditions = 105 +/- 40 g cm-2) and the U46619-stimulated 45Ca2+ uptake. It is
      concluded that inhibition, by hypoxia, of the U46619 contractile effect on sheep
      coronary artery rings may be in part due to inhibition of U46619-stimulated
      45Ca2+ uptake.

PMID- 7805781
TI  - Pharmacological evidence for a lack of role for protein kinase C in staurosporine
      induced morphological changes in embryonic Xenopus myocytes.
AB  - Staurosporine, an inhibitor of protein kinases, induced outgrowth of cultured
      embryonic Xenopus myocytes. The outgrowing membrane elicited by staurosporine was
      stained uniformly with fluorescein isothiocyanate-phalloidin. Pretreatment with
      microfilament-disrupting agents but not microtubule inhibitors inhibited
      staurosporine-induced membrane outgrowth. Microfilament assembly is thus required
      for the action of staurosporine. Protein kinase C activators did not antagonize
      the membrane outgrowing effect of staurosporine. Furthermore, none of H-7 (1-(5
      isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride), H-8 (N[2
      (methylamino)ethyl]-5-isoquinoline sulfonamide), sphingosine, phloretin,
      genistein or calmidazolium induced any significant morphological changes of
      embryonic myocytes, indicating that tyrosine kinases, protein kinase C, protein
      kinase A or calmodulin-dependent protein kinases may not be involved in the
      membrane outgrowing action of staurosporine. Total protein content of myocytes
      was not altered by staurosporine and protein or RNA synthesis inhibitors did not
      inhibit the membrane outgrowth induced by staurosporine. Furthermore, membrane
      outgrowth induced by staurosporine was less pronounced in older cultured myocytes
      or myocytes acutely isolated at later stages of tadpoles, indicating that there
      is different developmental susceptibility to the action of staurosporine.

PMID- 7805782
TI  - Effects of Ca2+ channel antagonists on chromaffin cell death and cytosolic Ca2+
      oscillations induced by veratridine.
AB  - Exposure of bovine chromaffin cells to 30 microM veratridine for 24 h led to 70
      80% cell death as reflected by phase contrast microscopy, trypan blue exclusion,
      lactate dehydrogenase (LDH) release and cell catecholamine contents. Na+
      deprivation, Ca2+ deletion or tetrodotoxin (5 microM) prevented the veratridine
      induced cell damage. Nimodipine and verapamil, but not omega-conotoxin GVIA
      afforded 20-30% protection. Flunarizine protected the cells by 80% and R56865 by
      60%. Stimulation of fura-2-loaded single bovine chromaffin cells with 30 microM
      of 1,1-dimethyl-4-phenylpiperazinium (DMPP) or 59 mM K+ caused fast increases in
      cytosolic Ca2+ concentrations, ([Ca2+]i). The [Ca2+]i rose from 0.1 to peaks of
      1.9 microM, which quickly declined to near basal levels with a t1/2 of around 30
      s. In spite of sustained stimulation with these two depolarizing agents, the
      [Ca2+]i remained low and did not undergo oscillations. In contrast, veratridine
      (30 microM) caused large and frequent oscillatory changes in the [Ca2+]i which
      were long-lasting and did not disappear even 30 min after washing out the toxin.
      The [Ca2+]i oscillations were reversibly suppressed by Na+ or Ca2+ removal and by
      5 microM tetrodotoxin. Selective L-type Ca2+ channel blockers (10 microM
      nimodipine or verapamil) or N-type Ca2+ channel blockers (1 microM omega
      conotoxin GVIA) did not affect the [Ca2+]i oscillations. In contrast, flunarizine
      or R56865 (10 microM each) suppressed the oscillations of [Ca2+]i. The results
      demonstrate that bovine chromaffin cells have the necessary machinery to develop
      prolonged and repetitive [Ca2+]i oscillations in the presence of veratridine;
      however, 'physiological' depolarizing stimuli did not cause
      oscillations.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7805783
TI  - On the mechanisms of 3-tert-butyl-4-hydroxyanisole- and its metabolites-induced
      cytotoxicities in isolated rat hepatocytes.
AB  - The cytotoxic effects of 3-tert-butyl-4-hydroxyanisole (BHA) and its metabolites,
      3-tert-butylhydroquinone (tBHQ) and 3-tert-butyl-4,5-dihydroxyanisole (BHA-OH),
      were investigated in freshly isolated rat hepatocytes. These compounds caused a
      time-dependent cell death accompanied by loss of intracellular ATP, glutathione
      (GSH) and protein thiols at concentration of 0.5 mM. Supplementation of the
      hepatocyte suspension with 5 mM N-acetylcysteine, a precursor of intracellular
      GSH, significantly delayed the onset of cytotoxicity induced by BHA-OH and tBHQ;
      the loss of intracellular ATP, GSH and protein thiols was also prevented.
      Although N-acetylcysteine did not affect BHA disappearance in the cell
      suspension, disappearance of tBHQ and formation of tBHQ-GSH conjugate were
      stimulated by N-acetylcysteine. In addition, N-acetylcysteine prevented BHA-OH
      disappearance and 3-tert-butyl-5-methoxy-1,2-benzoquinone (BHA-Q) formation. In
      isolated hepatic mitochondria, BHA, tBHQ and BHA-OH impaired respiration related
      to oxidative phosphorylation; tert-butylquinone (tBQ) and BHA-Q, quinones derived
      from tBHQ and BHA-OH, resulted in the significant inhibition of mitochondrial
      respiration. These results indicate that BHA-OH is the most cytotoxic followed by
      tBHQ and BHA and that protein thiols and mitochondrial respiratory system are
      important targets for BHA and its intermediates.

PMID- 7805784
TI  - Effect of ethanol treatment on indices of cumulative oxidative stress.
AB  - The effect of ethanol exposure upon several parameters relating to oxidative
      stress has been examined in brain and liver. A single administration of either
      acetaldehyde or ethanol was able to enhance rates of generation of reactive
      oxygen species in liver but this effect was not apparent in the cerebral cortex.
      Glutamine synthetase is especially sensitive to inactivation by free radicals and
      evidence for cumulative oxidative damage to this enzyme was found in liver and to
      a lesser extent in cerebral cortex. This enzyme was depressed in liver after both
      a single injection of acetaldehyde or ethanol, or after more extended dosing. The
      liver was also more susceptible than cerebral cortex, to pro-oxidant effects as
      judged by depression of glutathione after acute dosing with either solvent.
      Enzyme inhibition representing temporally summated oxidative events may be a more
      sensitive procedure than direct measurement of rates of formation of active
      oxygen species and may find especially utility in the detection of prolonged low
      level pro-oxidant activity.

PMID- 7805785
TI  - Philanthotoxin inhibits Ca2+ currents in rat hippocampal CA1 neurons.
AB  - The wasp venom philanthotoxin-4.3.3 (PhTX-4.3.3) is an antagonist of glutamate
      transmission in the insect as well as in the mammalian brain. It was recently
      shown that PhTX-4.3.3 inhibits the N-methyl-D-aspartate (NMDA) transmission in
      rat hippocampus. In this study we show that dideaza-philanthotoxin-12 (dideaza
      PhTX-12), an analogue of PhTX-4.3.3, is a potent antagonist of voltage-dependent
      Ca2+ currents in rat hippocampal CA1 neurons. At a concentration of 10 microM it
      reduces the Ca2+ current to 40%. Two voltage-dependent potassium currents, the A
      current and the delayed rectifier, were hardly affected by dideaza-PhTX-12,
      indicating selectivity of the drug for Ca2+ currents. As a consequence the
      philanthotoxins will inhibit the calcium influx via voltage dependent as well as
      NMDA mediaded calcium channels and thus reduce excitability in the hippocampus.

PMID- 7805787
TI  - Influence of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on
      mitochondrial respiration in rat liver during ischemia.
AB  - Effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors,
      pravastatin and simvastatin, on mitochondrial respiration in ischemic rat liver
      were examined. Either vehicle, pravastatin (2 or 4 mg/kg per day), or simvastatin
      (1 or 2 mg/kg per day) was orally administered for 3 weeks. Liver ischemia was
      induced by cessation of the systemic circulation for 60 min. Liver mitochondria
      were isolated and the respiration was determined by polarography using glutamate
      and succinate as substrates. In the vehicle-treated group, ischemia drcreased
      ZO3, respiratory control index (RCI: QO3/QO4), and ADP/O ratio. Pretreatments
      with pravastatin and simvastatin enhanced the decreases in QO3 measured with
      either glutamate or succinate, and in ADP/O ratio measured with succinate.
      Because of decreasing QO4, HMG-CoA reductase inhibitors did not modify the
      changes in RCI due to ischemia. There were no significant differences in
      respiratory indices between pravastatin- and simvastatin-treated groups. In
      conclusion, HMG-CoA reductase inhibitors may enhance respiratory impairment of
      liver mitochondria under pathophysiological conditions, such as ischemia.

PMID- 7805786
TI  - Two components in neurotoxicity by L-2-amino-3-phosphonopropionate in cultured
      cerebellar neurons.
AB  - Exposure of cultured cerebellar neurons to the putative metabotropic glutamate
      receptor antagonist L-2-amino-3-phosphonopropionate (L-AP3) for 24 h produced a
      neurotoxic effect which was prevented by the addition of the NMDA receptor
      antagonist (+)-10,11-dihydro-5-methyl-5-H-dibenzo-[a,d]-cyclohepten-5,1 0-imine
      hydrogen maleate (MK-801). MK-801 did also reduce neurotoxicity following 72 h
      exposure to L-AP3 neurotoxicity in the presence of MK-801 was antagonized by
      glutamate. Our results suggest that metabotropic glutamate receptors may play an
      important role in neuronal survival by controlling NMDA receptor-dependent as
      well as independent pathways.

PMID- 7805788
TI  - Pressor effect of ethanol in the isolated perfused human placental lobule.
AB  - Pharmacologically relevant concentrations of ethanol (0.01-0.3 g/%) were perfused
      via the fetal circulation in isolated human placental lobules. This resulted in a
      dose-related rise in fetal arterial pressure, which at 0.3 g/% ethanol, was 10.1
      +/- 1.1 mmHg above the pre-drug baseline. The pressor responses to ethanol were
      (i) rapid in onset, reaching a stable plateau within 5-10 min following
      administration, (ii) readily reversible by perfusion with drug-free media, (iii)
      non-tachyphylactic and (iv) largely inhibited by the cyclo-oxygenase inhibitor,
      inhibitor, indomethacin (5 microM). This pressor action of ethanol in the fetal
      circulation may contribute to the pathogenesis of the fetal alcohol syndrome as
      well as represent an underlying mechanism of ethanol-induced hypertension.

PMID- 7805789
TI  - Serum amyloid P component-induced cell death in primary cultures of rat cerebral
      cortex.
AB  - The influence of serum amyloid P component (SAP) on the survival of rat
      cerebrocortical cultures was tested. Cytotoxic cell death was examined on 8-9-day
      old cell cultures by phase contrast microscopy and quantified by the measurement
      of lactate dehydrogenase (LDH) leakage. SAP (16-48 nM) evoked a concentration
      dependent cell death within 24 h exposure. Our results suggest that SAP, as a
      constituent of cerebral amyloid deposits, may play a role in the pathomechanism
      of Alzheimer's disease.

PMID- 7805790
TI  - Comparison of copulatory behavior in male Syrian hamsters paired with one, two
      and four proestrous females each.
AB  - To increase the efficiency of Syrian hamster reproduction, individual males were
      caged with 2 or 4 estrous females. The fertility of the males caged with 2 or 4
      females was lower than that of those caged with a single estrous female. To
      clarify the cause of this, we observed the copulating behavior of males for 30
      minutes and examined their fertility. The median frequency of mounting,
      intromission and ejaculation was 27, 36 and 3, respectively, for the males caged
      with a single female, 37, 27 and 4, respectively, for the males caged with 2
      females and 13, 2 and 0, respectively, for the males caged with 4 females. Thus,
      these parameters were markedly reduced in the 1:4 mating group as compared with
      the 1:1 and 1:2 mating groups. In the 1:2 mating group, spermatozoa were detected
      in the vaginas of 12 of the 14 females, but only 6 of these 12 females delivered
      litters. In the 1:4 mating group, complete sequences of copulating behaviors were
      rarely seen, and spermatozoa were detected in the vaginas of only 6 of the 28
      females, and only one of these 6 females delivered. Thus, the efficiency of
      offspring production was not increased by raising the number of estrous females
      exposed to a male, probably due to a decrease in the frequency of male copulation
      in the presence of 2 females and due to inhibition of the male's copulating
      behavior in the presence of 4 females.

PMID- 7805791
TI  - [Optimal conditions for detection of calcitonin mRNA by in situ hybridization
      (ISH) method using a non-radioactive probe in the rat thyroid gland].
AB  - Optimal conditions for detection of calcitonin mRNA were examined by in situ
      hybridization (ISH) method using a non-radioactive probe in the rat thyroid
      gland. An oligonucleotide complementary to rat calcitonin mRNA was synthesized
      with a DNA synthesizer, labelled at 3'-end by using digoxigenin-11-deoxyuridine
      triphosphate (dUTP) and terminal transferase (Boehringer Mannheim), and used as a
      probe. Hybrid chains formed by probe and calcitonin mRNA were visualized by anti
      digoxigenin-alkaline phosphatase conjugate, nitroblue tetrazolium (NBT) and X
      phosphate (Boehringer Mannheim). To determine the optimal conditions for ISH,
      relations between tissue fixation and proteinase K treatment, and between
      hybridization temperature and time were mainly surveyed in the present study. As
      for the relation between tissue fixation and proteinase K treatment, good results
      were obtained in sections fixed by immersion in 10% formalin at 4 degrees C for 2
      hr, and digested with 1 microgram/milliliter proteinase K at 37 degrees C for 20
      min. Under this condition, the most intense signals were obtained after
      hybridization at 37 degrees C overnight. Alternative application of ISH and
      immunostaining to each of the adjacent sections revealed a small number of cells
      which were immunonegative but displayed hybridization signals.

PMID- 7805793
TI  - Cellular and soluble CD4 measurements in cynomolgus monkeys.
AB  - Anti-human CD4 monoclonal antibodies have been successfully used to label T
      lymphocytes in Cynomolgus monkeys by two different methods. A magnetisable bead
      separation was used prior to immunogold labelling of lymphocytes in one of the
      methods. In addition, an assay for soluble CD4 has been applied to the sera of
      these monkeys.

PMID- 7805792
TI  - Fine structure of the vomeronasal organ in the chinchilla (Chinchilla laniger).
AB  - Fine structure of the vomeronasal organ (VNO) was examined in the chinchilla
      (Chinchilla laniger) from a viewpoint of comparative anatomy. The VNO of
      chinchilla was a pair of tubular structure, about 6mm in length, and situated
      bilaterally along the base of the nasal septum. The VNO was encircled rostrally
      by the vomeronasal cartilage, but caudally by a bony capsule. The VNO
      communicated with the nasal cavity via a small pore at its rostral end, while it
      ended blindly at its caudal end. Its lumen was crescent to elliptical in a
      transverse plane, and lined medially with the vomeronasal sensory epithelium
      (VSE), but laterally with the vomeronasal respiratory epithelium (VRE).
      Jacobson's glands were tubulo-alveolar in type and distributed from the
      dorsolateral to the ventrolateral region of the VNO and opened with the duct to
      the lumen in the transitional region from the VSE to the VRE. Their secretions
      were periodic acid-Schiff (PAS)-positive but alcian blue (AB)-negative. The VSE
      consisted of sensory, supporting and basal cells. Supporting cells were
      characteristic of a large number of huge dense bodies in the perinuclear
      cytoplasm. The other ultrastructural features in sensory, supporting and basal
      cells of the VSE were similar to those in the previous reports. The VRE consisted
      of ciliated, non-ciliated and basal cells. Acinar cells of Jacobson's gland
      possessed two types of secretory granules. Secretory granules of one type were
      homogeneous and electronlucent, about 1,700nm in diameter, while granules of the
      other type were about 2,200nm in diameter, and various in electron density. The
      present findings suggest that the VNO is functionally active in the chinchilla.

PMID- 7805794
TI  - A special type of ganglion cells in the submucous plexus of mouse small
      intestine.
AB  - The perikarya of sensory neurons have been reported frequently from
      electrophysiological studies of the plexus submucosus of many mammalian digestive
      tracts, but the fine structural characteristics of those cells or ganglia have
      rarely been demonstrated. Therefore, we conducted an electron microscopic study
      in search of possible sensory perikarya in the plexus of the mouse small
      intestine. Many ganglion cells scattered over the plexus submucosus possessed a
      few areas of fine granules frequently adjacent to dense bodies in their
      perikaryonal cytoplasm, as revealed first by Wilson et al. [23], who were unable
      to explain the significance, of this finding. On the other hand, one type of
      ganglion with a special three-dimensional structure was observed in the same
      plexus. This ganglion was composed of one central perikaryon, one innermost
      cellular semiperfect cover of the Schwann cell, a middle two-layered cellular
      coat, an outer neuropil and an outermost external lamina. The surface of the
      central perikaryon, which differed from those of the other ganglion cells, was
      almost entirely covered with one Schwann cell, most probably for isolation from
      various kinds of external electrical and/or chemical inputs. Dumbbell-shaped
      vesicles containing endings that were presumed to be sensory, were frequently
      localized in the outer neuropil of this ganglion. It is likely that this
      perikaryon belongs to the sensory ganglion cells and so acts as an important
      factor in the peristaltic reflex arc.

PMID- 7805795
TI  - Identification of sublines of inbred strains of mice and assessment of genetic
      relationships between substrains or sublines by DNA fingerprinting.
AB  - Identification of substrains or sublines of inbred mice and assessment of genetic
      relationships among them were performed on the basis of DNA fingerprinting using
      M13 phage DNA as a probe. We used eight C57BL/6 sublines (J parallel Jcl, J
      parallel Jms, J parallel Slc, J parallel Nrs, J parallel Yok, Jah, N parallel
      Crj, N parallel Jcl) and eleven C3H/He sublines, (J, J parallel Jcl, J parallel
      Yok, J parallel Nrs, J parallel Jms, N, N parallel Jcl, N parallel Crj, Slc, Jah,
      Nrs). Two kinds of restriction endonucleases (HinfI and PstI) were used. It was
      found that: 1) DNA fingerprint within each subline showed identical patterns. 2)
      Most sublines of C57BL/6 and C3H/He could be identified using DNA fingerprinting
      with HinfI except between N parallel Crj and Slc, and among J, J parallel Nrs and
      J parallel Yok in C3H/He. DNA fingerprints with PstI endonucleases showed low
      polymorphic banding patterns. 3) A dendrogram constructed from DNA fingerprint
      patterns reflected generally the genealogy of the sublines used. 4) DNA
      fingerprinting, therefore, seemed to be suitable for the genetic monitoring and
      assessment of genetic relationships among sublines of inbred mice having close
      relationships.

PMID- 7805796
TI  - [Pathogenesis of spontaneous nephrosis in mice--urinary protein in nephrotic
      mice].
AB  - There is a paucity of model animals for naturally occurring nephrosis. The
      nephrotic mouse strain (ICGN) found from ICR mouse colony at National Institute
      of Health could be one of the most suitable model for nephrosis. We maintained
      the strain of mice which was originated from the hybrid between the nephrotic
      ICGN mice and ICR mice. Nephrosis is diagnosed with the presence of albumin band
      on SDS-PAGE of the urine. The detection of urinary albumin using SDS-PAGE could
      be valuable for early diagnosis of nephrosis in the mice. The total urinary
      protein concentration was determined on the course of nephrosis. The nephrotic
      mice showed slightly higher protein concentration between 2 and 6 days old as
      compared to control mice. Until 16 day old, it was maintained relatively low
      level. Thereafter, the total urinary protein increased gradually. However the
      diagnosis of nephrosis with total urinary protein alone may be limited due to the
      major urinary protein which can be detected even in normal rodents.

PMID- 7805797
TI  - [Blood volume determination in female SPF rats of Wistar--Imamichi strain by an
      extrapolation method with radioiodinated rat serum albumin].
AB  - The total blood volume of SPF female rats of Wistar-Imamichi strain, a strain
      that shows a 4-day estrous cycle at very high rates and is widely used in the
      study of reproductive biology in Japan, was estimated from blood radioactivity
      after the intravenous administration of 125I-rat serum albumin. The radioactivity
      of blood showed a rapid decrease until 10 min after injection and a slow decay
      thereafter. Radioactivity at time zero was estimated by extrapolation from this
      slow decay curve, and the blood volume was calculated. From 30 rats weighing 150
      300 g we obtained the following equation between blood volume (BLV) and body
      weight (BW), and a high correlation coefficient (r): BLV = 8,4007 + 0.0430 x BW,
      r2 = 0.92. The blood volume per body weight decreased linearly with increasing
      body weight, and we obtained the following equation: BLD/100 g BW = 12.25-0.0174
      x BW at r2 = 0.92.

PMID- 7805798
TI  - [A canine model of pancreas transplantation recipient following total
      pancreatectomy and associated lymphoproliferation].
AB  - An attempt was made to use a diabetic dog as a model recipient of pancreas
      transplantation. The diabetic state was induced by total pancreatectomy, and was
      shown to be stable by oral and intravenous glucose tolerance tests. In dogs that
      underwent total pancreatectomy under isoflurane anesthesia (GOI), blastogenesis
      of peripheral blood lymphocytes had a tendency to be reduced in comparison with
      no-treated dogs until 2 weeks after surgery. However, from 3 weeks after surgery,
      their responses became comparable to those of non-treated dogs. These results
      suggest that stable diabetes mellitus is induced, in dogs, by total
      pancreatectomy, and that this animal is a useful model of a pancreas
      transplantation recipient.

PMID- 7805799
TI  - [Strain- and age-associated changes in cytokine release from endotoxin-treated
      mouse monocytes].
AB  - Levels of cytokines released from endotoxin-mediated monocytes were investigated
      in mice of DBA/2, BALB/c, C57BL/6, C3H/He, ddY and ICR strains and in ICR mice of
      various ages (4-52 weeks old). Interleukin-1 alpha (IL-1 alpha), interleukin-1
      beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha) levels from
      monocytes were low in DBA/2 and BALB/c mice, and high in ddY and ICR strains. In
      addition, interleukin-6 (IL-6) levels were low in DBA/2, and high in ddY and ICR
      strains. Therefore, monocytes obtained from ddY and ICR strain mice released
      large amounts of cytokines as compared to those from the DBA/2 strain. The levels
      of IL-1 alpha, IL-1 beta and IL-6 released from monocytes of ICR mice were
      constant at 4-18 weeks old, and low at 26 and 52 weeks old. In contrast, the TNF
      alpha level was low at 18 weeks and high at 26 and 52 weeks. These results
      indicate that age-associated changes in cytokine release from monocytes correlate
      well with the cytokine levels in bone marrow.

PMID- 7805800
TI  - Histochemistry and immunohistochemistry of extracellular matrix of rat fetal
      Ductus arteriosus during the indomethacin-induced constriction.
AB  - Administration of anti-inflammatory non-steroidal drugs to pregnant animals
      causes constriction of the fetal ductus arteriosus (DA). To clarify the mechanism
      of the indomethacin-induced constriction of the rat fetal DA, extracellular
      matrix (ECM) components were observed by immunohistochemical techniques with
      antibodies 2B1, 6B6, 3B3, 9A2 and others to various kinds of proteoglycans (PGs).
      In the 10mg/kg group, the large PG revealed with antibody 2B1 was increased in
      the inner and outer media at constriction, and chondroitin 6-sulfate PG was
      strongly immunostained with antibody 3B3 as granular substances in the outer
      media, although no difference in stainability of chondroitin 4-sulfate PG
      revealed with the antibody 9A2 was observed between experimental and control
      groups. This suggests that the cells composing the fetal DA showed a tendency of
      proliferation and resultant production and aggregation of large PG with
      chondroitin 6-sulfate chains during constriction induced by indomethacin
      treatment.

PMID- 7805801
TI  - Interleukin-6 production by macrophages from BALB/c mice with a chronic infection
      of lactic dehydrogenase virus.
AB  - The production of interleukin-6 (IL-6), which is known as a B cell
      differentiation factor, by peritoneal macrophages from mice with a chronic lactic
      dehydrogenase virus (LDV) infection was compared with that from uninfected mice.
      The same amounts of IL-6 were detected in the culture supernatant of macrophages
      from LDV-infected mice as those from uninfected mice. Furthermore IL-6 production
      of macrophages from LDV-infected and uninfected mice was not affected by the
      addition of indomethacin. These results suggested that many immunological
      alterations seen in LDV-infected mice may not be due to, at least in part,
      altered IL-6 production ability of macrophages and the IL-6 production may not be
      affected by cyclooxygenase-derived products.

PMID- 7805802
TI  - The relationship between the hair cycle and the age or daily body weight gain in
      rabbits.
AB  - The relationship between the hair cycle and the age or daily body weight gain
      (daily gain) in rabbits was investigated. A survey of the ages of rabbits used
      for the dermal toxicological studies in our laboratories over the last 4 years
      was done, followed by an experiment to confirm the results of the survey.
      Although there seemed to be no relationship between the hair cycle and the daily
      gain, the results showed that the hair cycle was closely related to the age of
      the animal, and the animals in the telogen stage may be obtained efficiently at
      about 17 wks of age.

PMID- 7805803
TI  - [Effects of sex hormone on the dilatation of urinary tubule and acidophil body in
      NON mice].
AB  - The influences of sex hormones on the dilatation of the urinary tubules and
      acidophil bodies were histologically investigated in NON (Non-Obese Non-diabetic)
      mice. Although the dilatation of the proximal tubules and acidophil bodies in NON
      mice were observed only in female but not in male, a slight dilatation and a few
      bodies were also observed in castrated male NON mice. Moreover, in ovariectomized
      female NON mice the dilatation and bodies were less compared with intact female
      NON mice. Estradiol administration induced prominent dilatation and numerous
      acidophil bodies, while the administration of testosterone showed a complete
      preventive effect. Therefore, it is suggested that the dilatation of the tubules
      and the acidophil bodies can be profoundly influenced by sex hormones.

PMID- 7805804
TI  - [Changes in bone mineral density of lumbar vertebrae during a six-month interval
      in African green monkeys (Cercopithecus aethiops)].
AB  - Changes in measurements of lumbar vertebrae (L3-L5) during a six-month interval
      in African green monkeys were demonstrated using dual-energy X-ray absorptiometry
      (DEXA, DPX-alpha, Lunar, USA). Area, mean width and bone mineral content (BMC) of
      L3-L5 were measured, and bone mineral density (BMD) was calculated using 62
      laboratory-bred and 23 wild animals. Laboratory-bred animals were divided into 4
      groups according to their gender and age, and in addition, two groups of wild
      animals were constructed according to gender. Although no remarkable change in
      BMD of laboratory-bred animals aged less than two years was observed at a six
      month interval, significant decreases in BMD were detected in laboratory-bred
      animals aged over 6 years as well as in wild animals. Thus, DEXA seems to be
      useful for investigating the kinetics of BMD in aged animals during a relatively
      short period such as six-months.

PMID- 7805805
TI  - Increase in testis weight of hereditary dwarf rats (rdw/rdw) with advancing age.
AB  - Testis weight and seminal vesicle weight (relative to total body weight) in rdw
      rats and N rats were compared with advancing age. The results obtained were as
      follows 1) The increase in testis weight became remarkable at 15-16 weeks of age.
      The weight remained constant up to 23-30 weeks of age and decreased thereafter
      with age. 2) Seminal vesicle weight increased rapidly in rdw rat at 15-16 weeks
      of age, reflecting elevated androgen secretion and sexual maturation. 3) From the
      viewpoint of histology, one of causes of the increase in testis weight may be
      edema. The increase in testis weight coincided with the increase in androgen
      secretion at 15-16 weeks of age as suggested by the relative increase in seminal
      vesicle weight.

PMID- 7805806
TI  - Effects of streptozotocin-induced diabetes on receptive and proceptive behaviors
      in female rats.
AB  - Sexual dysfunction in diabetic men is thoroughly recognized, while not yet done
      in diabetic women. Recently, Streptozotocin (STZ)-induced male rats showed a
      significantly depressed copulatory behavior, compared with normal animals. We
      investigated whether STZ-induced diabetic female rats would produce observable
      deficits in sexual behavior. Results in the present study are the first to show
      that STZ-induced diabetic female rats have a depressed sexual behavior.

PMID- 7805807
TI  - Study on the detection of implantation site in rabbits.
AB  - In this study, an alkaline treatment was applied to the observation of
      implantation site in rabbits. Embryos in pregnant rabbits were stabbed to death
      on days 7, 8, 9, 10 and 18 of gestation. These animals were sacrificed on day 29.
      The uteri were removed, immersed in 2% sodium hydroxide and fixed with 10%
      buffered formalin. After the alkaline treatment, all of the implantation sites
      were clearly recognizable as white tissue since the other parts became fairly
      transparent. Even after the formalin fixation, all the implantation sites were
      similarly detectable. The mean area of implantation sites visibly increased after
      day 10. From all the results, the simple and accurate procedure including
      alkaline treatment was concluded to be useful for estimating implantation and
      pregnancy conditions in rabbits.

PMID- 7805808
TI  - Functional influence on sutural growth. A morphometric study in the anterior
      facial skeleton of the growing rat.
AB  - The aim of this study was to quantify the sutural response in the various parts
      of the rat's upper frontal viscerocranium and study the possible effects caused
      by reduced masticatory muscle function. Twenty growing male albino rats were
      randomly divided into two equal groups: one group (Hard Diet group) received the
      ordinary diet in a hard pellets form, while the other (Soft Diet group) a soft
      diet. The experimental period started just before the rats' pubertal growth spurt
      (28 days old) and its duration was 28 days. After death, the heads of the animals
      were taken for preparation of undecalcified frontal sections, 100 microns thick.
      Contact microradiographs of six representative homologous sections, for every
      animal in both groups, were prepared. The mean width, length, height, and
      interdigitation ratio of the internasal, naso-premaxillary, and interpremaxillary
      sutures, as well as the orientation of the bony surfaces of the naso-premaxillary
      suture were quantified on the contact microradiographs using the IBAS automatic
      image analysis system. The width of the sutural space was found to be
      significantly greater in the Hard Diet group than in the Soft Diet group in all
      the sutures studied (P < 0.01). No differences in the interdigitation of the
      sutures were found between the two groups, except in the internasal suture in the
      middle part of the snout, where the Hard Diet group exhibited increased
      interdigitations. The bony surfaces of the naso-premaxillary suture were
      significantly more parallelly-orientated in the animals with reduced masticatory
      muscle function (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7805809
TI  - Changes in blood circulation in teeth and supporting tissues incident to
      experimental tooth movement.
AB  - Fluorescent microspheres (FM) were used to semi-quantify the effect of
      orthodontic forces on blood flow in oral tissues in young rats. Forty-five
      animals had an orthodontic appliance inserted on the first maxillary molar on one
      side exerting a mesial force of approximately 50 g. Ten animals served as
      unoperated controls. On days 1, 3, 7, 14, and 21 after the start of the
      experiment, FM were injected into the left ventricle through an abdominal
      approach in the experimental and control animals. FM were counted in serial
      sections from the jaws in the periodontal ligament, pulp, and alveolar bone in a
      fluorescent microscope. The number of FM per tissue volume and/or tissue weight
      was taken as a measure of blood flow. The experimental side had significantly
      lower numbers of FM/mm3 in the periodontal ligament of the first and the second
      molar on the first day, compared with the contralateral side. However, a steady,
      significant increase in the number of FM/mm3 in the periodontal and pulpal
      tissues, and FM/mg in the alveolar bone could be observed on the third and
      seventh days on the experimental side of the first, second, and third molars
      compared with the contralateral side, while in the later stages the values of the
      two sides approached each other. The results of this study indicate that a
      localized experimental tooth movement initiates a more generalized blood flow
      response in the periodontal ligament, dental pulp and alveolar bone.

PMID- 7805810
TI  - Aetiological aspects of mandibular tooth agenesis--focusing on the role of nerve,
      oral mucosa, and supporting tissues.
AB  - The purpose of the present investigation was to consider possible aetiological
      aspects of mandibular tooth agenesis by comparing the pattern of mandibular molar
      and premolar agenesis with radiological evidence of the mandibular canal.
      Orthopantomograms from 33 children affected by agenesis of at least four premolar
      and/or molar teeth in the mandible were investigated. Three children were
      affected by ectodermal dysplasia. Two anthropological mandibles with absence of
      mandibular canals were included in the study for comparison. According to the
      investigation, agenesis should be divided into three groups, based on an analysis
      of agenesis location, the presence of nerve canals in the jaws, and finally, data
      on possible bone, skin and oral mucosa abnormalities. The three aetiological
      groups suggested are: agenesis related to nerve tissue, agenesis related to the
      oral epithelium, and agenesis related to the supporting tissue.

PMID- 7805811
TI  - Effect of timing and method of closure of isolated cleft palate on development of
      dental arches from 3 to 6 years of age.
AB  - Development of the dental arches from 3 to 6 years of age was followed in 120
      children with isolated cleft palate (ICP) and in 50 non-cleft (NONC) children. In
      60 of the ICP children the palate had been repaired at the age of 1.8 years (SD =
      0.2) and in the other 60 at the age of 1.1 years (SD = 0.1). In both groups the
      one-stage soft and hard cleft palate closure had been performed using the
      mucoperiosteal palatal V to Y push-back technique (Veau-Wardill-Kilner) or the
      Cronin modification. The purpose of this study was to compare the effect of the
      two different ages and the two different methods of palatal repair on the
      development of dental arches. The growth increment in maxillary canine and molar
      width, and posterior palatal height during the 3-year period was greater in the
      group with late palatal repair. In children with no secondary palatal repair,
      when the primary repair had been done with the V to Y method, the increase in
      maxillary canine width was greater than with the Cronin modification. On the
      other hand, when the V to Y technique was used, velopharyngoplasties were more
      frequent. The means of maxillary canine and molar width decreased in children
      with velopharyngoplasties, and increased in the others. Dental arches of ICP
      children were significantly smaller than those of NONC children, and the
      discrepancy increased during the period from 3 to 6 years of age, and increased
      more in the maxilla than in the mandible.

PMID- 7805812
TI  - Orthodontic facebow injuries and safety equipment.
AB  - Facebows are widely used in orthodontic treatment to reinforce anchorage, and in
      selected cases can be very useful and effective. However, they are not without
      their problems. Reports of injuries with this appliance have continued to appear
      in the literature since 1975. This article reports the results of a preliminary
      survey of 23 European countries confirming 10 eye injuries and includes a review
      of the current literature. The safety headgears currently available are examined
      and their adequacy, in the light of this survey, is assessed.

PMID- 7805813
TI  - The need for orthodontic treatment in the child population of the United Kingdom.
AB  - The effective management of a public dental health system requires accurate data
      on the needs of the population. Previous assessments of the levels of orthodontic
      treatment need in populations, by both epidemiologists and orthodontists, vary
      considerably. This paper presents the findings of two independent investigations
      into orthodontic treatment need in the United Kingdom using the Index of
      Orthodontic Treatment Need (IOTN, Brook and Shaw, 1989). The results indicate
      that approximately one-third of 11-12-year-olds were in objective need of
      orthodontic treatment. The basis for allocation to the treatment need groups was
      similar in both studies, as were the proportions of the most severe occlusal
      traits.

PMID- 7805814
TI  - Class III malocclusion in the deciduous dentition: a morphological and
      correlation study.
AB  - The craniofacial morphology of Class III children with a full deciduous dentition
      was investigated by means of a cephalometric and correlation study. A group of 69
      Class III subjects was compared to a group of 60 Class I subjects during the
      phase of the primary dentition. Each group was then divided into three age
      subgroups (4, 5, and 6 years) and a comparison was also performed between Class
      III and Class I subgroups. According to the results, early signs of Class III
      skeletal disharmony are present during the deciduous dentition phase. A larger
      mandibular body length (P < 0.001), a greater value for the ratio between the
      extent of the anterior cranial base and the mandibular body length (P < 0.001),
      and a forward positioning of the mandible (< P0.01 < 0.001) were consistently
      found in Class III children at the ages of 4, 5, and 6 years. A correlation
      analysis between all the cephalometric measurements in the Class III and Class I
      groups was then carried out, and the significance of the differences between
      correlation coefficients of the two groups was calculated. A distinctive Class
      III pattern of non-topographical associations between anterior cranial base and
      mandibular measurements could be detected.

PMID- 7805815
TI  - The characteristics of super-elastic Ni-Ti wires in three-point bending. Part I:
      The effect of temperature.
AB  - The load-deflection behaviour of a number of commercially available superalloy
      nickel-titanium orthodontic wires has been examined in three-point bending over
      the temperature range 5-50 degrees C. The loading and unloading curves and
      plateau regions are found to be closely related to temperature with the stiffness
      decreasing quite dramatically over a narrow temperature range. The position of
      this range depends on the material being tested as there are marked differences
      due to the differing processing methods of the manufacturer. Force values at
      mouth temperature can differ by 600 per cent for wires of the same nominal
      diameter made by different manufacturers.

PMID- 7805816
TI  - The characteristics of super-elastic Ni-Ti wires in three-point bending. Part II:
      Intra-batch variation.
AB  - Intra-batch variation in the load-deflection characteristics of 13 superalloy
      nickel-titanium wires has been examined at nominal mouth temperature (35 degrees
      C). The results indicate that although most of the superalloy nickel-titanium
      wires were undersized, the variation in diameter within a batch was of the same
      order as that reported for 18/8 stainless steel wire. The largest coefficients of
      variation for the intra-batch variation for the initial slope and the unloading
      plateau values were found to be approximately 7.5 and 10 per cent, respectively.
      A high degree of correlation was found between the mean slopes of the initial
      load-deflection curve in three-point bending at 35 degrees C and the mean wire
      diameter raised to the fourth power for the 13 superalloys wires, from which a
      value for Young's modulus (E) of 55.4 GPa was deduced on the basis that at this
      temperature the wires will have an austenitic structure and virtually identical
      compositions.

PMID- 7805817
TI  - [Medical-scientific information in Italy].

PMID- 7805818
TI  - Can social injustice be compensated adequately?

PMID- 7805819
TI  - [Health and social class: access to prevention or access to cure?].

PMID- 7805820
TI  - [Network of hardships and causal processes].

PMID- 7805821
TI  - [An index of HIV infection risk in the population].
AB  - The paper presents a risk index constructed on the basis of some sexual behaviour
      related variables. It is intended for measuring the risk of exposure to HIV
      infection for the general population. Variables are from a study on Lifestyle and
      Health conducted on a sample of the population living in the London, Edinburgh,
      and Glasgow metropolitan area by the Research Unit in Health and Behavioural
      Change at the Edinburgh University. The construction of the index has been
      realized through a delphi study which has collected information from a panel of
      AIDS national experts. Methodological problems in summarising information coming
      from several variables are discussed. The main task of the study is not to
      provide a total prediction of HIV infection in the population of Britain, but to
      assess the component which may stem from sexual behaviours when estimated from
      self-reports. Major findings are the consistency of the population in the "medium
      risk" group, that, if a spread of AIDS among the heterosexual population can be
      hypothesized, gives a rather pessimist scenario. Moreover, a trend analysis
      (possible because of the continuity in the data collection) shows an increase in
      this "medium risk" group, although the "high risk" group appears much less
      consistent (less than two percent) and slowly declining over time.

PMID- 7805822
TI  - [Results of a controlled randomized study on prevention of smoking habit in
      adolescents].
AB  - We describe the results of a randomized controlled study on the efficacy of a
      smoking prevention program based on behavioral methods (Waterloo Smoking
      Prevention Program 1, adapted). 792 children of 12-13 years of age from the
      Health District of Rozzano (MI) were the study base. The program was delivered
      directly by voluntary teachers during school classes. Two follow-up, at 18 and 36
      month from the end of the program were conducted using self-administered
      questionnaire and telephonic interviews. At 36 months the proportion of non
      smokers was higher in the intervention group (55% vs 44%; OR (adjusted for
      clustering) = 1.7; p = .03) and that of regular (at least one cigarette a week)
      smokers lower (22% vs 39%) than in the control group. We found no difference of
      effect between males and females students. Social pressure associated with
      starting to smoke (friends, sibsters, parents smokers) measured before
      intervention had no demonstrable influence on efficacy. We propose this kind of
      intervention for Italian students as an effective and low-cost program, even
      though more research is needed to maintain effectiveness of these kind of
      programs beyond adolescence.

PMID- 7805824
TI  - Compensation of occupational diseases and particularly of asbestos-related
      diseases among the European Community (EEC) countries.
AB  - The aim of the paper is to present some of the characteristics of the
      compensation systems in EEC countries and to focus on the compensation of
      asbestos-related diseases: for each country the diseases admitted for
      compensation, the date of introduction into the schedule, the number of
      compensations awarded and a comparison between compensations for mesothelioma and
      mortality are presented. The data have been collected in 1990-91 by asking for
      information to the Compensation Institutes. The results suggest that the
      objective of harmonisation of the compensation systems among European countries
      is far from being achieved and needs re-vitalisation. The gap between knowledge
      and public health action has been considerable in the compensation of asbestos
      related diseases, especially in the compensation of cancers. The results confirm,
      therefore, from a different perspective the validity of considering asbestos as a
      case study in public health. Finally, the Authors stress the serious situation in
      Italy with respect to updating the list of prescribed diseases as epidemiological
      data are available and to compensating occupationally related asbestos diseases.

PMID- 7805823
TI  - [A computer program to calculate expected cases in a dynamic cohort].
AB  - ECIDC (Expected Cases in Dynamic Cohorts) is a new interactive computerized
      programme in English for personal computers, created specifically to calculate
      expected cases in prospective cohort studies. Programmes available up to now have
      calculated the denominators of measurements of frequency, expressed in person
      years, using the recruitment date and exit date of each individual in the cohort.
      ECIDC, instead, calculates directly the number of expected cases, recognizing
      only the date of recruitment. The programme considers the aging of the cohort,
      estimates the effect due to competitive mortality and eliminates the expected
      deaths. Then, it calculates the expected cases by applying incidence or specific
      mortality from the reference population. ECIDC considers the period effects of
      both competitive mortality and expected incidence. When observed reference data
      is lacking, it compiles estimates of age-specific incidence and/or mortality
      trends. ECIDC can be used in power calculation for the cohort study. It also can
      be applied to simulation studies of incidence and mortality trends. The present
      paper tries out various simulations and shows the potential of the computerized
      programme.

PMID- 7805825
TI  - [Update of the Italian Table of Compensable Occupational Diseases].

PMID- 7805826
TI  - [Preliminary notes on the definition of several ethics guidelines in
      environmental epidemiology].

PMID- 7805827
TI  - On the site by which alpha-dendrotoxin binds to voltage-dependent potassium
      channels: site-directed mutagenesis reveals that the lysine triplet 28-30 is not
      essential for binding.
AB  - We constructed a synthetic gene encoding the published amino acid sequence of DTx
      from Dendroaspis angusticeps, a ligand of voltage-dependent postassium channels
      that facilitates neurotransmitter release. We expressed it in Escherichia coli as
      a fusion protein secreted in the culture medium. The recombinant DTx was
      generated in vitro by chemical treatment and recovered as two isoforms. One of
      them (rDTx), like the venom toxin, has an N-terminal pyroglutamate whereas the
      other (rQDTx) has a free N-terminal glutamine. Chromatographic differences
      between rDTx and natural DTx led us to re-examine the amino acid sequence of
      natural DTx. In contrast to what was previously published, position 12 was an Asp
      and not Asn. Despite this difference, rDTx and DTx had similar toxicity in mice
      and binding affinity to synaptosomes, suggesting that residue 12 is not important
      for DTx function. Nor is the N-terminal residue implicated in DTx function since
      rDTx and rQDTx also had similar biological activities. We also synthesized and
      expressed a mutant of the DTx gene in which the lysine triplet 28-30 was changed
      into Ala-Ala-Gly. The two resulting recombinant isoforms exhibited only small
      decreases in biological activity, excluding the possibility that the positively
      charged lysine triplet 28-30 of DTx is directly involved in the toxin functional
      site.

PMID- 7805828
TI  - The use of near-infrared charge-transfer transitions of low-spin ferric chlorins
      in axial ligand assignment.
AB  - The near-infrared magnetic circular dichroism spectra of some low-spin
      derivatives of ferric-octaethylchlorin substituted myoglobin have been recorded
      at cryogenic temperatures. The spectra, which include some of the lowest energy
      charge-transfer transitions ever observed for hemes, are clearly dependent upon
      the nature of the axial ligands present. While the results indicate that such
      spectra may have some practical utility in axial ligand assignment, as is now
      quite common practice for iron-porphyrin systems, there are some severe practical
      limitations to this protocol documented in the case of iron-chlorins.

PMID- 7805829
TI  - The 26S proteasome degrades mouse and yeast ornithine decarboxylase in yeast
      cells.
AB  - Eukaryotic cells possess two high-molecular-mass proteases, the 700 kDa, 20S
      proteasome, as well as the even larger 1,400 kDa, 26S proteasome. It has been
      demonstrated that ornithine decarboxylase is degraded, in vitro, by the 26S
      proteasome that contains the 20S protease as its catalytic core, but not by the
      free 20S proteasome. Recently, by demonstrating severe inhibition of mouse and
      yeast ODC degradation in a mutant yeast cell line, defective in the chymotripsin
      like activity of the yeast 20S proteasome, we implicated the 20S proteasome in
      the degradation of ODC, in vivo, in yeast cells. Here we show that the
      degradation of ODC is also severely inhibited in the mutant yeast cell lines,
      cim3-1 and cim5-1, containing a specific lesion in subunits that are unique to
      the yeast 26S proteasome. We therefore, conclude, that as illustrated in vitro,
      also in intact cells, it is the 26S proteasome, not the free 20S proteasome, that
      degrades ODC. We also demonstrate, that while deficiency in the proteasome
      chymotrypsine-like activity (in the yeast pre1-1 mutant) inhibits the degradation
      of both yeast and mouse ODCs, deficiency in the peptidyl-glutamyl-peptide
      hydrolyzing (PGPH) activity inhibits only yeast ODC degradation. Similarly, we
      have noted that whereas the putative ATPase activity of both the CIM3 and CIM5
      subunits is essential for the degradation of mouse ODC, only that of the CIM3
      subunit is required for the degradation of yeast ODC. These results suggest
      differential utilization of individual proteasomal subunits in the recognition
      and degradation of individual short-lived proteins.

PMID- 7805830
TI  - Purification and crystallization of the ternary complex of elongation factor
      Tu:GTP and Phe-tRNA(Phe).
AB  - Elongation factor Tu (EF-Tu) is the most abundant protein in prokaryotic cells.
      Its general function in protein biosynthesis is well established. It is a member
      of the large family of G-proteins, all of which bind guanosine phosphates (GDP or
      GTP) as cofactors. In its active GTP bound state EF-Tu binds aminoacylated tRNA
      (aa-tRNA) forming the ternary complex EF-Tu:GTP:aa-tRNA. The ternary complex
      interacts with the ribosome where the anticodon on tRNA recognises a codon on
      mRNA, GTPase activity is induced and inactive EF-Tu:GDP is released. Here we
      report the successful crystallization of a ternary complex of Thermus aquaticus
      EF-Tu:GDPNP and yeast Phe-tRNA(Phe) after its purification by HPLC.

PMID- 7805831
TI  - Identification of defensin binding to C1 complement.
AB  - In human serum we found strong defensin binding to the complexes of activated C1
      complement (C1) and C1 inhibitor (C1i). Purified C1q, activated C1 tetramer
      (r2s2) and C1i did not bind defensin. When r2s2 was dissociated by EDTA, only the
      activated C1s (C1s) bound defensin. Binding of defensins to C1 complement
      represents a newly recognized bridge between the complement- and phagocyte
      mediated host defenses, and a potential mechanism for protecting infected tissue
      from cytotoxic injury by defensin.

PMID- 7805832
TI  - Electrogenic amino acid exchange via the rBAT transporter.
AB  - A cDNA clone was isolated from rabbit renal cortex using DNA-mediated expression
      cloning, which caused alanine-dependent outward currents when expressed in
      Xenopus oocytes. The cDNA encodes rBAT, a Na-independent amino acid transporter
      previously cloned elsewhere. Exposure of cDNA-injected oocytes to neutral amino
      acids led to voltage-dependent outward currents, but inward currents were seen
      upon exposure to basic amino acids. Assuming one charge/alanine, the outward
      current represented 38% of the rate of uptake of radiolabelled alanine, and was
      significantly reduced by prolonged preincubation of oocytes in 5 mM alanine. The
      currents were shown to be due to countertransport of basic amino acids for
      external amino acids using the cut-open oocyte system. This transport represents
      a major mode of action of this protein, and may help in defining a physiological
      role for rBAT in the apical membrane of renal and intestinal cells.

PMID- 7805833
TI  - Fourier transform infrared spectrum of the radical cation of beta-carotene
      photoinduced in photosystem II.
AB  - A Fourier-transform infrared (FTIR) spectrum of the radical cation of beta
      carotene photoinduced in photosystem II (PSII) membranes was obtained at 80K
      under oxidizing conditions, by utilizing the light-induced FTIR difference
      technique. Formation of the beta-carotene cation was monitored with the
      electronic absorption band at 993 nm. An FTIR spectrum of a chemically-generated
      beta-carotene cation in chloroform was also measured and compared with the
      spectrum of PSII. Since the FTIR bands of carotenoid cation have characteristic
      features with strong intensities, they can be useful markers in studying the
      reaction of carotenoid in PSII.

PMID- 7805834
TI  - Identification of a fatty acyl responsive regulator (FarR) in Escherichia coli.
AB  - FarR (formerly P30) has been identified as a fatty acid and fatty acyl-CoA
      responsive DNA-binding protein. It is encoded by the farR gene (g30) in the
      citric acid cycle gene cluster of E. coli (gltA-sdhCDAB-sucABCD-farR). The
      amplified FarR protein specifically bound to the farR promoter (PfarR) and
      exhibited weak binding to the citrate synthase and lipoamide dehydrogenase
      promoters. Binding at PfarR was abolished by long-chain fatty acids and their CoA
      thioesters. In DNaseI footprints, FarR binding at PfarR protected two sites, each
      characterised by two related 10-bp direct repeats. It is suggested that FarR
      autoregulates farR expression and may modulate citric acid cycle expression in
      response to long-chain fatty acids.

PMID- 7805835
TI  - Residues responsible for distinct biological functions are characterized by
      different statistical features of sequential and spatial neighborhoods: a
      thermolysin example.
AB  - An investigation of the functional topography of thermolysin was carried out
      using frequency analysis of its primary and tertiary structures. The statistical
      validity of this approach was estimated for the enzyme active site, the substrate
      binding pocket, the inter-domain interface and calcium-binding sites'
      predictions. We showed that frequency analysis of primary structure could be
      employed to predict the localization of contiguous parts of the inter-domain
      interface. The same approach appears to be unsuitable to a search for
      conformation-dependent enzyme active sites and substrate-binding pockets. In
      contrast, frequency analysis of the spatial neighborhood is not effective for
      predicting the inter-domain interface as distinct from the active site, substrate
      binding pocket and calcium-binding sites. These differences should be taken into
      account when investigating and understanding protein structure-function
      relationships.

PMID- 7805836
TI  - The number of amino acid residues in hydrophilic loops connecting transmembrane
      domains of the GABA transporter GAT-1 is critical for its function.
AB  - Transporter proteins consist of multiple transmembrane domains connected by
      hydrophillic loops. As the importance of these loops in transport processes is
      poorly understood, we have studied this question using the cDNA coding for GAT-1,
      a Na+/Cl(-)-coupled gamma-aminobutyric acid transporter from rat brain. Deletions
      of randomly picked non-conserved single amino acids in the loops connecting
      helices 7 and 8 or 8 and 9 result in inactive transport upon expression in HeLa
      cells. However, transporters where these amino acids are replaced with glycine
      retain significant activity. The expression level of the inactive mutant
      transporters was similar to that of the wild-type, but one of these, delta Val
      348, appears to be defectively targetted to the plasma membrane. Our data are
      compatible with the idea that a minimal length of the loops is required,
      presumably to enable the transmembrane domains to interact optimally with each
      other.

PMID- 7805837
TI  - A structural determinant of differential sensitivity of cloned inward rectifier
      K+ channels to intracellular spermine.
AB  - Large subtype-specific differences in the sensitivity of cloned inward-rectifier
      K+ channels of the IRK1, BIR10 and ROMK1 subtype to being blocked by
      intracellular spermine (SPM) are described. It is shown, by site-directed
      mutagenesis, that the four orders of magnitude larger SPM sensitivity of BIR10
      channels compared to ROMK1 channels may be explained by a difference in a single
      amino acid in the putative transmembrane segment TMII. This residue, a negatively
      charged glutamate in BIR10, is homologous to the residue in IRK1 and ROMK1 which
      has previously been shown to change gating properties and Mg2+ sensitivity.
      Differential block by physiological SPM concentrations is suggested as a major
      functional difference between subtypes of inward-rectifier K+ channels.

PMID- 7805838
TI  - Precursor-mediated opening of translocation pores in chloroplast envelopes.
AB  - Direct electrical measurements on native chloroplast envelopes reveal that a full
      length chloroplast precursor protein causes an increase in the conductivity of
      the envelope membranes, due to its transit sequence. The conductivity is not
      influenced by a truncated precursor protein incapable of efficient translocation,
      suggesting precursor-mediated opening of translocation pores in chloroplast
      envelopes.

PMID- 7805839
TI  - Vitellogenin gene of the silkworm, Bombyx mori: structure and sex-dependent
      expression.
AB  - Vitellogenin of Bombyx mori is a precursor of major yolk protein synthesized in
      the female fat body at larval-pupal ecdysis. The gene for B. mori vitellogenin is
      composed of seven exons interspersed by six introns. Developmental profile of the
      primary transcript of the gene indicated that the biosynthesis of B. mori
      vitellogenin is regulated transcriptionally in a sex- and stage-dependent manner
      in the fat body. The Arg-X-Arg-Arg sequence, which conforms to the recognition
      site of mammalian furin, occurs in a region just upstream of the putative
      proteolytic cleavage site of B. mori previtellogenin.

PMID- 7805840
TI  - The reversion of highly tumorigenic cell lines to non-tumorigenic phenotype is
      associated with c-jun down-expression.
AB  - Using model spontaneously reverting cell lines, c-jun, junB, junD and c-fos
      oncogene expression was investigated. c-jun, but not junB, junD or c-fos, was
      overexpressed in highly tumorigenic clones. The reversion of cells to the non
      tumorigenic phenotype resulted in a dramatic decrease in c-jun expression. CAT
      assays revealed that c-jun overexpression in tumorigenic cells was associated
      with higher transcription activity. No correlation between c-jun oncogene
      expression and AP-1 transcription factor activity in tumorigenic and non
      tumorigenic clones was found.

PMID- 7805841
TI  - Cloning and characterization of the human V3 pituitary vasopressin receptor.
AB  - Arginine-vasopressin (AVP) plays a determinant role in the normal ACTH response
      to stress in mammals. We cloned a human cDNA coding a 424 amino acid G-protein
      coupled receptor structurally related to the vasopressin/oxytocin receptor
      family. When expressed in COS cells, this receptor binds AVP with a high affinity
      (Kd = 0.55 +/- 0.13 nM) and is functionally coupled to phospholipase C.
      Competition studies with peptidic or non peptidic AVP analogues reveal that it is
      pharmacologically distinct from V1a and V2 AVP receptors and therefore it is
      designated V3. RT-PCR analysis shows that the human V3 receptor is expressed in
      normal pituitary and also in kidney, but is undetectable in liver, myometrium and
      adrenal gland. Northern blot analysis reveals a approximately 4.8 kb messenger in
      human corticotropic pituitary adenomas.

PMID- 7805842
TI  - The 'pterocarpan synthase' of alfalfa: association and co-induction of vestitone
      reductase and 7,2'-dihydroxy-4'-methoxy-isoflavanol (DMI) dehydratase, the two
      final enzymes in medicarpin biosynthesis.
AB  - Vestitone reductase and 7,2'-dihydroxy-4'-methoxy-isoflavanol (DMI) dehydratase
      are the two final enzymes in medicarpin biosynthesis in alfalfa (Medicago
      sativa). Although two independent enzymes, vestitone reductase and DMI
      dehydratase can be loosely associated in low ionic strength buffers, presumably
      by a weak protein-protein interaction. The activities of vestitone reductase and
      DMI dehydratase increased approximately 3-fold 6 hours after elicitor treatment
      in alfalfa suspension cell culture. The activities remained at maximal levels for
      40 hours, correlating with a steady increase in the medicarpin content of the
      cells. Medicarpin produced in vitro from vestitone by the action of vestitone
      reductase and DMI dehydratase was found to be (-)-medicarpin (6aR,11aR
      medicarpin), possessing the same stereochemistry as medicarpin produced in vivo.

PMID- 7805843
TI  - Purification and characterization of the inhibitory subunit (delta) of the ATP
      synthase from Micrococcus luteus.
AB  - Subunit delta was isolated from the ATP-synthase from Micrococcus luteus strain
      (ATCC 4698). delta, in the case of M. luteus F0F1-ATPase, acts as an inhibitor of
      ATP hydrolysis and thus resembles subunits in E. coli and chloroplast ATP
      synthase. After treatment with 1.5 M LiCl the ATP-synthase dissociated, and
      subsequently subunit delta (27 kDa) was purified by hydrophobic interaction
      chromatography. Inhibition of ATP-synthase lacking delta by addition of delta
      showed non-competitive kinetics with a Ki of approximately 5.9 nM. Subunit
      epsilon from chloroplast F1, which corresponds functionally to the M. luteus F0F1
      delta, and chloroplast delta were tested for ATPase inhibitory activity by
      addition to the partially delta-depleted ATP-synthase from M. luteus. CF1-epsilon
      inhibited M. luteus ATP-synthase up to 80%, whereas CF1-delta did not show any
      influence.

PMID- 7805844
TI  - Tissue specificity of mitochondrial F0F1-ATPase activity of Lilium longiflorum
      plant.
AB  - A large difference was found in the activities of oligomycin-sensitive
      mitochondrial F0F1-ATPase isolated from different tissues of Lilium longiflorum
      plants. The enzyme activity of F0F1-ATPase in pollen was the highest, while that
      in bulbs was the lowest. When ATPases were cross-reconstituted from F1-ATPases
      and F1-depleted submitochondrial particles (SMP), ATPases reconstituted from F1
      depleted pollen SMP showed the higher activity regardless of the source of F1
      ATPase. Fatty acid compositions of phospholipids in SMP were also different
      between bulbs and pollen. These suggest that the F0 portion and/or its
      environment are important for regulation of F0F1-ATPase activity in L.
      longiflorum plant.

PMID- 7805845
TI  - Isolation of a putative receptor from Zea mays microsomal membranes that
      interacts with the G-protein, GP alpha 1.
AB  - The C-terminal region of a heterotrimeric G-protein alpha-subunit is known to be
      one of the principal determinants governing its interaction with its cognate
      receptor. Use of an oligopeptide corresponding to the fifteen C-terminal residues
      of the Arabidopsis G alpha-subunit (GP alpha 1), as an affinity ligand, led to
      the resolution of a tightly binding 37 kDa membrane polypeptide from detergent
      solubilised Zea microsomal fraction membranes. An identical polypeptide bound
      tightly to an affinity matrix containing recombinant GP alpha 1 protein as
      ligand: binding and release of this 37 kDa protein was dependent on the
      activation state of GP alpha 1 which was regulated by inclusion or omission of
      the G-protein activator AlF-4. Finally, the isolated 37 kDa protein was labelled
      with the lectin concanavalin A, indicating it to be glycosylated. These data are
      consistent with the identity of the 37 kDa membrane polypeptide as a receptor
      that interacts with the Zea homologue of GP alpha 1.

PMID- 7805846
TI  - Molecular characterization of human and bovine endothelin converting enzyme (ECE
      1).
AB  - A membrane-bound protease activity that specifically converts Big endothelin-1
      has been purified from bovine endothelial cells (FBHE). The enzyme was cleaved
      with trypsin and the peptide sequencing analysis confirmed it to be a zinc
      chelating metalloprotease containing the typical HEXXH (HELTH) motif. RT-PCR and
      cDNA screens were employed to isolate the complete cDNAs of the bovine and human
      enzymes. This human metalloprotease was expressed heterologously in cell culture
      and oocytes. The catalytic activity of the recombinant enzyme is the same as that
      determined for the natural enzyme. The data suggest that the characterized enzyme
      represents the functional human endothelin converting enzyme ECE-1.

PMID- 7805848
TI  - Cdc25 is not the signal receiver for glucose induced cAMP response in S.
      cerevisiae.
AB  - The Ras/cAMP pathway in the yeast S. cerevisiae couples the cell cycle of this
      unicellular organism to the availability of nutrients. Glucose derepressed S.
      cerevisiae cells respond to glucose addition by an intracellular rise in cAMP. In
      the prevailing model, yeast Ras plays a similar role to that of heterotrimeric G
      proteins coupled to cell surface receptors. A crucial element of this model is
      that the exchanger, Cdc25 is activated by glucose. Such activation would result
      in a glucose-dependent rise in GTP-bound Ras concentration. We here show, in
      contrast to this view, that Cdc25 cannot be the receiver of the glucose signal.
      We suggest that the Ras-GTP/cyclase complex is the molecular element directly
      receiving the signal while Cdc25-dependent exchange constitutes a prerequisite
      for complex formation.

PMID- 7805847
TI  - ADP ribosyl cyclase activity of a novel bone marrow stromal cell surface
      molecule, BST-1.
AB  - Human BST-1, a bone marrow stromal cell surface molecule, is a GPI-anchored
      protein that facilitates the growth of pre-B cells. The deduced amino acid
      sequences of human and mouse BST-1 show around 30% homology with those of CD38
      and Aplysia ADP ribosyl cyclase. Therefore, like CD38, BST-1 might possess ADP
      ribosyl cyclase activity. Here, we report the establishment of a stable
      transformant CHO cell line, which secretes truncated human soluble BST-1, and
      show that purified soluble BST-1 displays both ADP ribosyl cyclase and cADPR
      hydrolase activities.

PMID- 7805850
TI  - Poly (ADP-ribose) polymerase inhibits DNA replication by human replicative DNA
      polymerase alpha, delta and epsilon in vitro.
AB  - The influence of poly (ADP-ribose) polymerase (PARP) and poly ADP-ribosylation on
      DNA synthesis supported by human replicative DNA polymerase (DNA pol) alpha,
      delta, and epsilon has been examined using the replication system containing
      poly(dA)4500-oligo(dT)12-18 as the template primer. PARP alone inhibited the pol
      activities in a dose-dependent manner even in the presence of the accessory
      factors for DNA pol delta, proliferating cell nuclear antigen (PCNA) and
      activator 1 (Al; RF-C). Both DNA pol alpha and epsilon activities were decreased
      approximately 10-fold under the poly ADP-ribosylating condition. In contrast, DNA
      synthesis by DNA pol delta holoenzyme was not affected by poly ADP-ribosylation
      like prokaryotic DNA pol's. The analysis of poly(dT) formed by DNA pol alpha and
      epsilon indicated that poly ADP-ribosylation mainly reduced the frequency of
      replication. These observations suggest a possibility that PARP acts as a
      negative regulator for the initiation of DNA replication upon cellular DNA
      damage.

PMID- 7805849
TI  - Evidence for the ligand-induced conversion from a dimer to a tetramer of the
      granulocyte colony-stimulating factor receptor.
AB  - An extracellular portion of granulocyte colony-stimulating factor (G-CSF)
      receptor, which contains an immunoglobulin-like (Ig) domain and cytokine receptor
      homologous (CRH) region, was secreted into the medium using Trichoplusia ni
      Autographa californica nuclear polyhedrosis virus system. The gene product was
      purified to homogeneity mainly as a dimer (85 kDa) using G-CSF affinity column
      chromatography and gel filtration HPLC, although the product existed as a monomer
      (45 kDa) in the medium. Scatchard analyses suggested that only the dimer had high
      affinity ligand binding (Kd = about 100 pM), which is comparable with the Kd
      value of the cell surface receptor. The binding of G-CSF to Ig-CRH induced its
      tetramerization (200-250 kDa). The molecular composition of the tetrameric
      complex showed a stoichiometry of four ligands bound to four Ig-CRH. These
      results suggested that the oligomeric mechanism of the G-CSF receptor differs
      from that reported for growth hormone (GH) receptor, although CD spectrum
      spectroscopy suggested that the Ig-CRH has a GH receptor-like structure.

PMID- 7805852
TI  - Thyrsiferyl 23-acetate is a novel specific inhibitor of protein phosphatase PP2A.
AB  - Thyrsiferyl 23-acetate (TF23A), a cytotoxic compound from marine red alga, has
      been shown to potently and specifically inhibit serine/threonine protein
      phosphatase 2A (PP2A) with IC50 values of 4-16 microM, depending on the enzyme
      concentration. TF23A did not affect activity of protein phosphatase 1 (PP1), 2B
      (PP2B), 2C (PP2C), or protein tyrosine phosphatases (PTP) up to 1 mM. It
      inhibited PP2A activity in a crude extract of a human T cell line, Jurkat cell,
      as well as the purified catalytic subunit. Thus, TF23A proved to be a novel
      useful probe for clearly distinguishing the activity of PP2A from those of the
      other protein phosphatases in crude cell extracts and identification of cellular
      processes that are regulated by PP2A.

PMID- 7805853
TI  - Classical, novel and atypical isoforms of PKC stimulate ANF- and TRE/AP-1
      regulated-promoter activity in ventricular cardiomyocytes.
AB  - Cultured neonatal rat ventricular myocytes were co-transfected with expression
      plasmids encoding protein kinase C (PKC) isoforms from each of the PKC
      subfamilies (classical PKC-alpha, novel PKC-epsilon or atypical PKC-zeta)
      together with an atrial natriuretic factor (ANF) reporter plasmid. Each PKC had
      been rendered constitutively active by a single Ala-->Glu mutation or a small
      deletion in the inhibitory pseudosubstrate site. cPKC-alpha, nPKC-epsilon or aPKC
      zeta expression plasmids each stimulated ANF-promoter activity and expression of
      a reporter gene under the control of a 12-O-tetradecanoylphorbol 13-acetate
      response element (TRE). Upregulation of the ANF promoter is characteristic of the
      hypertrophic response in the heart ventricle and a TRE is present in the ANF
      promoter. Thus all subfamilies of PKC may have the potential to contribute to
      hypertrophic response in cardiomyocytes.

PMID- 7805851
TI  - Covalent anchoring of proteins onto gold-directed NHS-terminated self-assembled
      monolayers in aqueous buffers: SFM images of clathrin cages and triskelia.
AB  - N-Hydroxysuccinimide-terminated self-assembled monolayers with linear (CH2)10
      chains were prepared on ultraflat Au(111) surfaces from
      dithiobis(succinimidylundecanoate). These monolayers, which are covalently
      chemisorbed to gold via thiolate bonds, form a highly reactive amino-group
      specific carpet at the liquid-solid interface. Proteins bind to it covalently in
      aqueous buffers under mild conditions; this provides a (general) procedure for
      protein immobilization for scanning probe microscopy. Using this technique, we
      have obtained what we believe are the first scanning force microscopy images of
      clathrin cages and of their in situ disassembly, yielding typical triskelia under
      non-denaturing conditions.

PMID- 7805854
TI  - Regulation by glucose of the biosynthesis of PC2, PC3 and proinsulin in (ob/ob)
      mouse islets of Langerhans.
AB  - The prohormone convertases PC2 and PC3 have been shown to catalyze the processing
      of proinsulin to insulin in pancreatic beta-cells. In these studies we have
      compared the effects of glucose on PC2 and PC3 biosynthesis in freshly isolated
      islets from normal and hyperglycemic (ob/ob) mice. In contrast to normal islets
      [Alarcon, et al. (1993) J. Biol. Chem. 268, 4276] the biosynthesis of both PC2
      and PC3 is stimulated by glucose, parallel to the stimulation of proinsulin in
      the (ob/ob) islets. Inhibition of PC2 biosynthesis by glucose in normal islet non
      beta-cells may obscure stimulation of PC2 biosynthesis in normal islet beta
      cells.

PMID- 7805855
TI  - Interaction of phosphorylated elongation factor EF-2 with nucleotides and
      ribosomes.
AB  - The intrinsic fluorescence emission spectrum of elongation factor EF-2 due to the
      7 Trp residues was not modified after complete phosphorylation of the factor by
      the specific Ca2+/Calmodulin-dependent kinase III. The effect of nucleotide
      binding on this fluorescence revealed differences between phosphorylated and
      unmodified EF-2. Low concentrations of GTP had a smaller quenching effect on the
      fluorescence of phosphorylated EF-2 than on the fluorescence of unmodified EF-2,
      whereas GDP had exactly the same quenching effect on the fluorescence of both
      samples. These results suggest that phosphorylation of EF-2 decreased its
      affinity for GTP but not for GDP. Ability of phosphorylated EF-2 to form a
      ternary complex with ribosomes in the presence of a non-hydrolysable GTP analog
      and its ability to protect ribosomes against ricin-inactivation were both
      decreased to the same extent. The lower affinity of phosphorylated EF-2 for GTP
      could be responsible for a weaker and/or incorrect interaction of the factor with
      the ribosome, in particular with the ricin-site of the 28-S rRNA assumed to be
      involved in translocation initiation.

PMID- 7805856
TI  - P-glycoprotein-mediated efflux of hydroxyrubicin, a neutral anthracycline
      derivative, in resistant K562 cells.
AB  - Hydroxyrubin (OH-Dox), a neutral doxorubicin derivative that is only slightly
      cross-resistant to doxorubicin (Dox), can be actively pumped out of resistant
      K562 cells by P-glycoprotein (P-gp). This efflux is saturable and can be
      inhibited by verapamil. The Michaelis constant is equal to 2 +/- 0.5 microM.
      However, the efficiency of P-gp in pumping out the drugs is 2.5 times less for OH
      Dox than for Dox. This shows that in order to be pumped out by P-gp a molecule
      does not necessarily have to have a basic center. The mean influx coefficient for
      the drug is 5 times higher for OH-Dox than for Dox. In conclusion, the degree of
      resistance of analogs is related not only to their ability to be recognized and
      transported by P-gp but also, and probably essentially, to their kinetics of
      uptake. Both parameters have to be taken into account in the rational design of
      new compounds capable of overcoming multidrug resistance.

PMID- 7805857
TI  - Constitutive activation of cyclic AMP but not phosphatidylinositol signaling
      caused by four mutations in the 6th transmembrane helix of the human thyrotropin
      receptor.
AB  - Four different somatic mutations (F631C, T632I, D633E, and D633Y) in the putative
      6th transmembrane helix of the human thyrotropin receptor (TSHR) were recently
      described in hyperfunctioning thyroid adenomas [Porcellini et al. (1994) J. Clin.
      Endocrinol. Metab. 79, 657-661]. We transiently expressed these mutant receptors
      in Cos-7 cells and measured [125I]TSH binding, basal and TSH-stimulated cAMP
      production, and phosphatidylinositol hydrolysis. The concentration of receptors
      expressed at the cell surface was lower for the mutants than for the wild type
      (WT) TSHR. Compared to the WT, all four mutant receptors caused a marked increase
      in basal cAMP levels, but did not increase basal production of inositol
      phosphates. This suggests that autonomous thyroid function and adenoma formation
      may be related to constitutive activation of the cAMP pathway alone. A cluster of
      conserved residues at the base of the 6th transmembrane helix of the TSHR and
      other glycoprotein hormone receptors appears important for maintaining an
      inactive receptor conformation.

PMID- 7805858
TI  - Nanomolar concentrations of nitric oxide reversibly inhibit synaptosomal
      respiration by competing with oxygen at cytochrome oxidase.
AB  - Nitric oxide (NO) reversibly inhibited oxygen consumption of brain synaptosomes.
      Inhibition was reversible, occurred at the level of cytochrome oxidase, and was
      apparently competitive with oxygen, with half-inhibition by 270 nM NO at oxygen
      concentrations around 145 microM and by 60 nM at around 30 microM O2. Isolated
      cytochrome oxidase was inhibited by similar levels of NO. These levels of NO are
      within the measured physiological and pathological range for a number of tissues
      and conditions, suggesting that NO inhibition of cytochrome oxidase and the
      competition with oxygen may occur in vivo.

PMID- 7805859
TI  - A 66-kDa protein associated with epidermal growth factor receptor is a
      proteolytic fragment of phosphoinositide-specific phospholipase C.
AB  - It is shown that in the A431 cells, EGFR is co-immunoprecipitated with a group of
      proteins recognized by antibodies to phospholipase C gamma. These are 145- and 47
      kDa proteins corresponding to phospholipase C gamma and Nck, respectively, and an
      unidentified 66-kDa protein. The association of phosphoinositide-specific
      phospholipase C gamma and 66-kDa protein to EGFR was observed in the A431 cells
      with or without the EGF treatment. Trypsin peptide maps of these two proteins are
      similar so it is assumed that the 66-kDa protein is related to phospholipase C
      gamma.

PMID- 7805860
TI  - Negative and positive effects of CpG-methylation on Xenopus ribosomal gene
      transcription in vitro.
AB  - Methylation of cytosine-residues in the sequence CpG affects the expression of
      many genes and generally correlates with reduced transcription. The ribosomal
      genes of Xenopus laevis were among the first genes to be studied with respect to
      their DNA methylation, and a loss of methylation during embryonic development
      correlated with the onset of transcription. Nevertheless, highly methylated
      ribosomal genes were transcribed at normal levels when injected into oocyte
      nuclei, and thus transcription of these genes was generally assumed to be
      insensitive to CpG-methylation. Here I show that Xenopus ribosomal gene
      transcription can be repressed by cellular factors binding to meCpG, similarly as
      it has been described for transcription by RNA polymerase II. In the absence of
      these repressors, however, CpG-methylation has a direct positive effect on RNA
      polymerase I-promoter activity.

PMID- 7805861
TI  - Localization of a regulatory region on the 5'-untranslated region of human
      hepatoma HepG2 gamma-glutamyltransferase mRNA and response to dexamethasone and
      antisense oligonucleotide treatment.
AB  - We are reporting the functional analysis of the 5'-untranslated region (5'UTR) of
      human hepatoma HepG2 gamma-glutamyltransferase (GGT) mRNA. Transient expression
      of hybrid GGT-luciferase reporter gene mutants in HepG2 shows that this 5'UTR
      acts as a tissue-specific translational enhancer. A domain of 173 bases
      containing a steroid hormone response element (HRE) is responsible for the
      enhancing effect, which can be amplified by addition of dexamethasone at 10(-6)
      M. Furthermore, the regulatory role of the 5'UTR is demonstrated by interaction
      with sense and antisense oligonucleotides.

PMID- 7805862
TI  - Impaired copper binding by the H46R mutant of human Cu,Zn superoxide dismutase,
      involved in amyotrophic lateral sclerosis.
AB  - Several point mutations in the gene coding for human Cu,Zn superoxide dismutase
      have been reported as being responsible for familial amyotrophic lateral
      sclerosis (FALS). However, no direct demonstration has been provided for a
      correlation between total superoxide dismutase activity and severity of the FALS
      pathology. In order to get a better insight into the mechanism(s) underlying the
      FALS phenotype, we have investigated the activity and the copper binding
      properties of the single mutant H46R, which is associated with a Japanese form of
      FALS. We have shown that this mutant is structurally stable but lacks significant
      enzyme activity and has impaired capability of binding catalytic copper. The
      mutant protein can be fully reconstituted with copper in vitro but its ESR
      spectrum displays an axial shape quite different from that of the wild-type.

PMID- 7805863
TI  - Cloning and characterization of the Drosophila melanogaster CDK5 homolog.
AB  - The D. melanogaster homolog of mammalian CDK5 has been cloned and its chromosomal
      location determined. The gene for Cdk5 consists of 4 exons separated by 3 short
      introns ranging in size from 61-160 bp. Northern blot analysis revealed a single
      mRNA of approximately 1.6 kb that is expressed at highest levels in the adult
      fly. The putative amino acid sequence for Drosophila Cdk5 predicts a protein with
      a mass of approximately 32 kDa that is 77% identical to its mammalian counter
      parts. Drosophila Cdk5 gene is located in polytene chromosomal region 52BC of the
      right arm of chromosome 2. This study provides the framework for a molecular
      genetic analysis of CDK5 function.

PMID- 7805864
TI  - Cyclic AMP formation in Tetrahymena pyriformis is controlled by a K(+)
      conductance.
AB  - Responses of the cAMP generating system of Tetrahymena to changes in the
      concentrations of external [K+] or [Ca2+] ions were examined. When Tetrahymena
      are equilibrated in high [K+] buffers, intracellular levels of cAMP decreased to
      40% within 2 h. Hyperpolarization of the cells by dilution of external [K+] to
      one-eighth of its original concentration instantly stimulated intracellular cAMP
      formation. Manipulations of the K+ resting conductance of Tetrahymena by
      equilibration in buffers of different K+ content greatly affected the
      responsivity of the adenylyl cyclase. Hyperpolarization of the cell by addition
      of Ca2+ also resulted in a rapid generation of cAMP. Blockade of K+ conductances
      by the K+ channel blockers tetraethylammonium, quinine, and Cs+, dose-dependently
      inhibited hyperpolarization-stimulated cAMP formation. The data indicate that a
      hyperpolarization-activated K+ current is directly coupled to adenylyl cyclase
      regulation.

PMID- 7805865
TI  - A new human leukemia cell 8.2 kDa differentiation factor: isolation and primary
      structure.
AB  - A new 8.2 kDa differentiation factor has been purified to homogeneity from the
      cultural media of human myelogenous HL-60 leukemia cells induced by retinoic
      acid. cDNA clones encoding this factor were isolated from a cDNA library prepared
      from HL-60 differentiated cells and their nucleotide sequence has been
      determined. The deduced amino acid sequence of the differentiation factor
      molecule consists of 54 amino acid residues. The protein is shown to be
      glycosylated. It was shown by Northern blot experiments that the level of
      poly(A)+ RNA with a length of 450 nucleotides was higher in differentiated cells
      than in non-differentiated cells.

PMID- 7805866
TI  - Cloning of the Na(+)-translocating NADH-quinone reductase gene from the marine
      bacterium Vibrio alginolyticus and the expression of the beta-subunit in
      Escherichia coli.
AB  - The Na(+)-translocating NADH-quinone reductase purified from the marine bacterium
      Vibrio alginolyticus is composed of three subunits, alpha, beta and gamma. From
      the N-terminal amino acid sequences of each subunit and its polypeptide fragment
      obtained by partial digestion with V8 protease, oligonucleotides corresponding to
      forward and reverse primers for each gene (NQR A, B and C) encoding the alpha,
      beta and gamma subunit, respectively, were synthesized. Using these primers, a
      part of each gene was amplified from the chromosomal DNA of V. alginolyticus by a
      PCR method, and the PCR products were used for the cloning of the NQR gene in
      lambda phage. Among the subclones selected by probe C, the expression of the beta
      subunit as a gene product was detected in Escherichia coli membranes by activity
      staining and Western blotting.

PMID- 7805867
TI  - Cloning and sequencing of four structural genes for the Na(+)-translocating NADH
      ubiquinone oxidoreductase of Vibrio alginolyticus.
AB  - Oligonucleotide probes based on the N-terminal amino acid sequences of the NqrA
      and NqrC subunits were used to clone genes for the Na(+)-dependent NADH
      ubiquinone oxidoreductase complex from Vibrio alginolyticus. Four consecutive
      ORFs were identified encoding subunit proteins of 48.6, 46.8, 27.7 and 22.6 kDa,
      respectively (NqrA-D). A further ORF, showing 71% homology to the BolA protein of
      Escherichia coli, was located upstream. From sequence comparisons, we conclude
      that the Na(+)-dependent NADH-ubiquinone oxidoreductase complex of V.
      alginolyticus is clearly distinct from the corresponding H(+)-dependent enzymes
      of both prokaryotes and eukaryotes.

PMID- 7805869
TI  - Characterization and determination of the redox properties of the 2[4Fe-4S]
      ferredoxin from Methanosarcina barkeri strain MS.
AB  - Ferredoxin was purified from methanol-grown Methanosarcina barkeri strain MS. It
      was isolated as a dimer with a subunit molecular weight of 6,200. The protein
      contained 7.4 mol iron and 7.2 mol acid-labile sulfur per monomer. In the reduced
      state the ferredoxin exhibited an EPR spectrum characteristic of two spin-coupled
      [4Fe-4S]1+ clusters. The EM of the [4Fe-4S]2+:1+ couple was -322 mV +/- 3 mV vs.
      NHE at 21 degrees C and pH 7.0. The midpoint potential was temperature but not pH
      dependent. At the physiological temperature of 37 degrees C the Em was -340 mV.

PMID- 7805868
TI  - Nucleotide sequence and analysis of the mouse SPC3 promoter region.
AB  - Insulin is converted from the higher molecular weight proprotein, proinsulin by
      highly specific proteolytic cleavage at two dibasic amino acid sites. SPC3 and
      SPC2, two recently identified prohormone convertase that are specifically
      expressed in beta cells and other neuroendocrine cells, appear to be responsible
      for those cleavages. We have sequenced the 5'-upstream region of the SPC3 gene
      and examined its promotor/enhancer activity and most of several deletion mutants
      in several cell lines. This region contains no CAAT box but has several non
      functional TATA-like sequences and several putative transcriptional regulatory
      elements, including AP-1, Sp1 and cAMP response elements. These features are not
      unlike those of the human SPC2 upstream region. In beta TC3 insulinoma cells, the
      sequence between the EcoRI (620 bp) and NsiI (702 bp) sites seems to be important
      for gene expression, while the sequence between the NsiI and DraI (775 bp) sites
      may contain strong enhancer element(s).

PMID- 7805870
TI  - Primary structure of a multimeric protein, homologous to the PEP-utilizing enzyme
      family and isolated from a hyperthermophilic archaebacterium.
AB  - A large protein complex (approx. 2000 kDa) was found in the cytosol of the
      hyperthermophilic archaebacterium Staphylothermus marinus. The purified protein
      was shown to be a homomultimer of 93 kDa subunits, the primary structure of which
      was determined by nucleotide sequence analysis. The protein belongs to the family
      of phosphoenolpyruvate-utilizing enzymes and represents the first member
      characterized in archaebacteria. Its homomultimeric organisation differs from the
      typically dimeric structure of its eubacterial and eukaryotic counterparts.

PMID- 7805871
TI  - Identification of a novel protein tyrosine phosphatase with sequence homology to
      the cytoskeletal proteins of the band 4.1 family.
AB  - Use of the polymerase chain reaction (PCR) in conjunction with Southern
      hybridization, using probes corresponding to known phosphatase sequences,
      resulted in the identification of rat cDNA clones encoding a novel protein
      tyrosine phosphatase which was termed rPTP2E. The cDNAs comprise 5,543 bp and
      predict a polypeptide of 1175 amino acids possessing a single catalytic domain at
      its C-terminus. The N-terminal region of the deduced polypeptide displays high
      sequence homology to the cytoskeleton-associated proteins of the band 4.1 family.
      A variant form, termed rPTP2E1, was also identified which contains the catalytic
      domain only. rPTP2E and rPTP2E1 were expressed in various rat tissues,
      particularly abundantly in adrenal glands. The catalytic domain of PTP2E was
      expressed in Escherichia coli and was shown to possess specific protein tyrosine
      phosphatase activity. The identification of rPTP2E suggests the existence of a
      subfamily of band 4.1 domain-containing PTPs which may play an important role in
      signalling pathway and control of cytoskeletal integrity.

PMID- 7805872
TI  - Mechanism of the cytolytic action of Pseudomonas aeruginosa cytotoxin:
      oligomerization of the cytotoxin on target membranes.
AB  - Pseudomonas aeruginosa cytotoxin (CTX) is thought to be a pore-forming
      polypeptide of 29 kDa. To study whether CTX assembles into oligomer on target
      membranes, we solubilized membrane-bound toxin with 1% sodium dodecyl sulfate
      (SDS) at 25 degrees C and analyzed its molecular size using SDS-polyacrylamide
      gel electrophoresis and immunoblot analysis. The results indicate that CTX forms
      a complex of approximately 145 kDa on the surface of erythrocytes and lipid
      vesicles, and that the complex formation is closely correlated with the toxin
      induced permeabilization of target membranes. Thus, CTX may assemble into a pore
      forming oligomer on target membranes.

PMID- 7805873
TI  - New structures in complex formation between DNA and cationic liposomes visualized
      by freeze-fracture electron microscopy.
AB  - Structures formed during interaction of cationic liposomes and plasmid DNA were
      studied by freeze-fracture electron microscopy and their morphology was found to
      be dependent on incubation time and DNA concentration. These structures were
      formed with liposomes composed of DC-Chol and DOPE after 30 min incubation at
      DNA:lipid concentrations encompassing maximal transfection activity. They
      resembled liposome complexes (meatballs) and additionally bilayer-covered DNA
      tubules (spaghetti), whereby the DNA-tubules were found to be connected to the
      liposome complexes as well as occurring free in the suspension. At later times
      and higher DNA-to-liposome ratios the complexes grow larger while their membranes
      become discontinuous, allowing the self-encapsulation of the DNA. The relative
      transfection potency of the various morphologically distinct structures is
      discussed.

PMID- 7805874
TI  - A novel peridinin-chlorophyll a protein (PCP) from the marine dinoflagellate
      Alexandrium cohorticula: a high pigment content and plural spectral forms of
      peridinin and chlorophyll a.
AB  - A new type of peridinin-chlorophyll a protein (PCP) was isolated from the marine
      dinoflagellate Alexandrium cohorticula. Unlike previous studies. PCP was obtained
      as a single component in the presence of a protease inhibitor. The monomer had a
      molecular mass of 37 kDa with 12 peridinin molecules associated with 2 chl a
      molecules. This pigment content was much higher than that reported previously. We
      observed a partial amino acid sequence of the N-terminus that is novel among
      photosynthetic pigment-protein complexes. Magnetic circular dichroism clearly
      indicated that chl a in PCP had monomeric features. Multiple spectral components
      were suggested for both chl a and peridinin. Based on the high pigment content,
      the optical properties were compared with those for a reported PCP containing 4
      chl a and 1 peridinin.

PMID- 7805875
TI  - Brefeldin A inhibits insulin-dependent receptor redistribution in HIRcB cells.
AB  - Brefeldin A (BFA) is a potent inhibitor of intracellular vesicle traffic. We have
      investigated the effects of BFA on the traffic of the insulin receptor in HIRcB
      cells, a cell line derived from Rat-1 fibroblasts that over-expresses a normal
      human insulin receptor. We report here that insulin-dependent receptor
      redistribution is inhibited by BFA and that this drug has no effects on the
      insulin-dependent redistribution of the receptor. Auto-phosphorylation of the
      insulin receptor and the stimulation of mitogen-activated protein kinase (MAPK)
      by insulin were not affected by treatment with the drug. The effects of BFA were
      further shown to require addition of the drug prior to the addition of insulin.
      BFA added 10 min after stimulation with insulin had no effects on the
      redistribution of the receptor. Dose-response studies demonstrated that the
      effects of BFA were half-maximal at a dose of 1 microgram/ml and maximal at about
      10 micrograms/ml. These findings suggest that BFA blocks an early step in the
      chain of events that lead to insulin receptor internalization without affecting
      the interactions of the receptor with insulin, the stimulation of the tyrosine
      kinase activity of the receptor by the hormone, or other insulin-regulated
      signalling pathways, such as the activation of MAPK.

PMID- 7805876
TI  - The N-terminus of amine oxidase of Hansenula polymorpha contains a peroxisomal
      targeting signal.
AB  - Here we describe the identification of the targeting sequence of peroxisomal
      amine oxidase (AMO) of H. polymorpha. Deletion analysis revealed that essential
      targeting information is located within the extreme N-terminal 16 amino acids.
      Moreover, this sequence can direct a reporter protein to the peroxisomal matrix
      of H. polymorpha. The N-terminal 16 amino acids of AMO contain a sequence with
      strong homology to the conserved PTS2 sequence. Therefore, AMO is considered to
      be a PTS2 protein.

PMID- 7805877
TI  - Calcium/calmodulin-dependent regulation of the NH2-terminal F-actin binding
      domain of utrophin.
AB  - The cytoskeletal proteins utrophin, dystrophin and alpha-actinin are predicted to
      form antiparallel dimers thus potentially bringing their NH2-terminal F-actin
      binding domains in close proximity to their EF-hand containing COOH-terminal
      domains. This arrangement would allow for calcium-dependent regulation of F-actin
      binding. We tested this hypothesis by determining the effect of the ubiquitous
      calcium binding protein calmodulin on their F-actin binding capabilities. Binding
      of the NH2-terminal F-actin binding domain of utrophin to F-actin was inhibited
      by increasing concentrations of calmodulin in a calcium-dependent manner. The
      homologous F-actin binding domains from dystrophin and alpha-actinin were not
      regulated by calmodulin in the presence or absence of calcium. These findings
      have implications for the structural organisation of utrophin dimers and also for
      the replacement of dystrophin by over-expression of utrophin in dystrophic
      muscle.

PMID- 7805878
TI  - Molecular cloning of human cathepsin O, a novel endoproteinase and homologue of
      rabbit OC2.
AB  - A 1670-bp cDNA coding for a novel human cysteine protease has been isolated from
      a monocyte-derived macrophage cDNA library. This cDNA predicts a 329-amino acid
      preprocathepsin with more than 50% identity to both human cathepsin S and
      cathepsin L and 94% identity to a rabbit cDNA, termed OC2, recently isolated from
      osteoclasts. Based on its high homology to OC2, we have named the human enzyme
      cathepsin O. Cathepsin O mRNA was identified as a single approximately 1.7 kb
      transcript in cultures of 15-day-old monocyte-derived macrophages, but was not
      expressed in human monocytes or alveolar macrophages. When transfected into COS-7
      cells, cathepsin O displayed potent endoprotease activity against fibrinogen at
      acid pH. This novel endoprotease may play an important role in extracellular
      matrix degradation.

PMID- 7805879
TI  - Pro-oxidant effects of 7-hydroperoxycholest-5-en-3 beta-ol on the copper
      initiated oxidation of low density lipoprotein.
AB  - In low density lipoproteins (LDL) supplemented with aged cholesterol and oxidized
      in the presence of Cu2+, an increase of the lipid oxidation parameters was
      observed compared with pure cholesterol-enriched LDL. A compound, identified as 7
      hydroperoxycholesterol (7HPC), isolated from aged cholesterol and added to LDL,
      reproduced the above effects. The results indicate that the pro-oxidant effect of
      7HPC is dependent on the hydroperoxy group since the corresponding alcohol
      derivative, 7 alpha-hydroxycholesterol, had no such effect. These data suggest
      that among the LDL-associated lipid peroxides, cholesterol peroxides may have
      important implications in the susceptibility of this lipoprotein to oxidation.

PMID- 7805880
TI  - Adhesion molecules: a new target for immunoliposome-mediated drug delivery.
AB  - The anti-ICAM-1 monoclonal antibody F10.2 was conjugated to liposomes to target
      to cells expressing the cell adhesion molecule ICAM-1. We demonstrate that F10.2
      immunoliposomes bind to human bronchial epithelial cells (BEAS-2B) and human
      umbilical vein endothelial cells (HUVEC) in a specific, dose- and time-dependent
      manner. It appears that the degree of ICAM-1 expression is the limiting factor in
      the degree of immunoliposome binding to the cells. These results are a first step
      in the strategy for specific drug delivery to target sites characterised by
      increased expression of adhesion molecules.

PMID- 7805881
TI  - Identification of glutamate beta 54 as the covalent-catalytic residue in the
      active site of glutaconate CoA-transferase from Acidaminococcus fermentans.
AB  - In the course of glutamate fermentation by Acidaminococcus fermentans glutaconate
      coenzyme A-transferase catalyzes the transfer of CoAS- from acetyl-CoA to (R)-2
      hydroxyglutarate, forming (R)-2-hydroxyglutaryl-CoA. Glutamate (E) 54 of the beta
      subunit was postulated to be directly involved in catalysis by formation of a
      CoASH ester intermediate [(1994) Eur. J. Biochem., in press]. In order to prove
      this preliminary result, the following mutations, beta E54A, beta E64A, beta E54Q
      and beta E54D, were introduced by mismatch oligonucleotide priming. As expected,
      beta E54A was inactive (0.02% of the wild-type), whereas beta E64A and beta E54D
      were active, 30% and > 7%, respectively. However, no CoASH intermediate was
      detected in the latter mutant, indicating a change in the catalytic mechanism.
      The activity of the beta E54Q mutant increased from 1% to almost 100% upon
      incubation with acetyl-CoA and glutaconate at 37 degrees C within 40 h. Hence,
      the substrates induced the conversion of the mutant glutamine residue into the
      glutamate residue of the wild-type enzyme.

PMID- 7805882
TI  - Sequence similarities of phytochrome to protein kinases: implication for the
      structure, function and evolution of the phytochrome gene family.
AB  - Phytochrome, the best characterised plant photoreceptor, is encoded by a small
      multigene family within the plant kingdom. The different phytochrome types are
      composed of a conserved light-sensing chromophore domain of about 80 kDa and a
      less-conserved C-terminal domain of about 50 kDa. The C-terminus of phytochrome
      of the moss Ceratodon purpureus is homologous to the catalytic domain of
      eukaryotic serine/threonine or tyrosine protein kinases; in contrast, for all
      other phytochromes (conventional phytochromes) sequence similarities within the C
      terminal domain to the catalytic domain of bacterial histidine kinases have been
      reported. We performed careful sequence comparisons of the putative catalytic
      domains of phytochrome with each other, with authentic serine/threonine, tyrosine
      and with histidine kinases. We report that conventional phytochromes exhibit
      structural elements of the catalytic domains of both histidine and, to a lesser
      extent, of serine/threonine and tyrosine kinases. The significance of these
      observations is discussed in the framework of the structure, function and
      evolution of phytochrome.

PMID- 7805883
TI  - Cooperativity-regulated parallel pathways of the bacteriorhodopsin photocycle.
AB  - The paper demonstrates that the actinic light density dependence of the
      millisecond part of the bacteriorhodopsin (BR) photocycle at high pH predicts a
      model, which is the same in the sequence of the intermediates as concluded
      previously on the basis of double flash experiments [1992, FEBS Lett. 311, 267
      270]. This model consists of the Mf-->N-->BR and M(s)-->BR parallel pathways, the
      relative yields of which are regulated by cooperative interaction of the BR
      molecules. The decay of M(s) is always slower than the decay of Mf and described
      as a direct reprotonation of the Schiff-base from the bulk, and the recovery of
      the ground-state nearly at the same time. M(s) is decomposed into M'f and M's.
      The first does not reprotonate, and similarly to Mf, it is suggested to be before
      the conformational change (switch), which latter process would be just before the
      decay of Mf. A simple way for the determination of the kinetics is also used.
      This confirms that the amount of N decreases with increasing fraction cycling and
      shows that the decay rate of N is independent of the fraction cycling. The
      differences in the kinetics are compared to each other, and they seem to allow a
      new way of kinetic evaluation at least under special conditions. The aim of this
      paper was briefly explained in my poster presented on the VIth International
      Conference on Retinal Protein (see [14]).

PMID- 7805884
TI  - Hydrogen peroxide preferentially enhances the tyrosine phosphorylation of
      epidermal growth factor receptor.
AB  - We found that hydrogen peroxide (H2O2) enhances EGF receptor tyrosine
      phosphorylation in intact cells as well as solubilized membrane of an EGF
      receptor hyperproducing cell line NA. An antioxidant MnCl2 effectively inhibited
      this enhancement. Interestingly, overall phosphorylation of the EGF receptor
      enhanced by H2O2 was half that of the EGF-enhanced phosphorylation when the
      receptor immunoprecipitated from [32P]orthophosphate-labeled cells was examined.
      Tryptic phospho-peptide mapping of these receptors revealed that EGF enhanced the
      phosphorylation on five specific residues including serine 671, 1,046 and 1,047,
      threonine 669 and tyrosine 1,173, whereas H2O2 enhanced the phosphorylation
      remarkably on tyrosine 1,173 and three other residues and only moderately on
      serine 1,046 and 1,047 and threonine 669. Thus, H2O2 preferentially enhances the
      tyrosine phosphorylation of EGF receptor through oxidant stress.

PMID- 7805885
TI  - Autoprocessing of HSV-1 protease: effect of deletions on autoproteolysis.
AB  - HSV-1 protease is involved in virus maturation. It is autoproteolytic and
      processed from a larger precursor. We have analysed the autoproteolysis of UL26
      ORF and shown by in vitro-coupled transcription and translation that the UL26
      encoded protein is processed, leading to the accumulation of its N-terminal
      domain. The deletion of the residues 245-248 in UL26 ORF abolishes the N-terminal
      cleavage but not the C-terminal processing. Deletion of the 3' end of UL26
      prevents production of the mature protease. These results strongly suggest that
      autoproteolysis is achieved in a defined order.

PMID- 7805886
TI  - Recombinant expression and domain structure of the Rna1 protein from
      Schizosaccharomyces pombe.
AB  - The amino acid sequence of Rna1p, a yeast protein implicated in the maturation
      and/or nucleocytoplasmic transport of RNA, is characterised by the presence of
      eight leucine-rich repeats (LLRs) as well as two intervening repeats of a
      different type and a highly acidic C-terminal region. Limited proteolysis of
      purified Rna1p expressed recombinantly in bacteria reveals that the C-terminal
      extension but not the region containing the two types of repeats is highly
      accessible to proteolytic attack and that the C-terminal region most likely
      harbours (a) low affinity Ca(2+)-binding site(s). These results are indicative of
      the domain structure of the Rna1p molecule, with the repeats and the C-terminal
      region being accessible for different interactions.

PMID- 7805887
TI  - Mixing antifreeze protein types changes ice crystal morphology without affecting
      antifreeze activity.
AB  - All three fish antifreeze protein types (I, II and III) inhibit the growth of ice
      to form hexagonal bipyramidal ice crystals of characteristic morphology. Mixtures
      of these different antifreezes produced ice crystals of hybrid shapes and
      dimensions, consistent with the different antifreeze types binding to the same
      ice surfaces. The activity of the mixtures was independent of the proportions of
      the iso-active antifreeze protein stocks present, indicating that the different
      antifreezes neither attenuated nor potentiated each other's activity. We suggest
      that antifreeze protein molecules are independently active and do not require
      protein-protein interactions for ice-binding.

PMID- 7805888
TI  - Isolation and structural characterization of enkephalins in the brain of the
      rhynchobdellid leech Theromyzon tessulatum.
AB  - This paper reports the purification of four peptides related to enkephalins from
      the brain of the leech Theromyzon tessulatum. After reverse-phase HPLC
      purification, the sequence of the enkephalins (YGGFM, YGGFL, FM, FL) was
      established by a combination of automated Edman degradation, electrospray mass
      spectrometry measurement, and co-elution experiments in reverse-phase HPLC with
      synthetic peptides. ELISA titrations performed on each purified peptide indicated
      that the major amount was borne by the leucine-enkephalin. The ratio of leucine
      enkephalin and methionine-enkephalin of 2:1 is in line with previous
      immunocytochemical data obtained on T. tessulatum brains. The presence of
      enkephalins in T. tessulatum, an animal belonging to the oldest group of
      coelomate metazoans (the Annelida) establishes the very ancient phylogenetic
      origin of opioids and their conservation in the course of evolution.

PMID- 7805889
TI  - Selective inhibition of cytosine-DNA methylases by polyamines.
AB  - We have advanced the hypothesis that polyamines affect DNA methylation and thus
      promote the expression of developmentally controlled genes. We demonstrate that
      the activity of cytosine-DNA methyltransferases HpaII, HhaI, HaeIII and SssI is
      inhibited by physiological concentrations of polyamines. On the other hand,
      activity of the adenine-DNA methyltransferase EcoRI, and restriction enzymes
      HpaII, HhaI, HaeIII and EcoRI, is insensitive to polyamine concentrations up to
      40 mM. Our results indicate that the effect of polyamines on cytosine-DNA
      methyltransferases is rather selective and suggest a possible mode of action in
      vivo.

PMID- 7805890
TI  - Shift from fetal-type to Alzheimer-type phosphorylated Tau proteins in SKNSH-SY
      5Y cells treated with okadaic acid.
AB  - Tau proteins are abnormally phosphorylated in Alzheimer's disease. Pathological
      Tau proteins named PHF-Tau 55, PHF-Tau 64, and PHF-Tau 69, are the main
      constituents of the paired helical filaments (PHF). When treating SKNSH-SY 5Y
      cells with okadaic acid (OA), Tau 55 protein was clearly induced whereas Tau 64
      protein was only faintly induced. Here, we show that the absence of Tau 69 could
      be explained by the fact that adult isoforms containing N-terminal inserts are
      not detected. Phosphorylation is similar for untreated cellular Tau proteins and
      fetal Tau proteins, while OA cell treatment transformed fetal-type into Alzheimer
      type phosphorylated proteins.

PMID- 7805891
TI  - Identification of yeast MAS17 encoding the functional counterpart of the
      mitochondrial receptor complex protein MOM22 of Neurospora crassa.
AB  - MOM22 of Neurospora crassa was suggested to be required for the transfer of
      mitochondrial precursor proteins from the receptors to the protein translocation
      machinery. We isolated a yeast mutant the viability of which depended on the
      expression of the introduced N. crassa MOM22 gene. The mutant cells showed
      defects in protein import into mitochondria when the cells were depleted of
      MOM22. By screening for suppressor genes for the mutant, we could identify the
      yeast gene MAS17 encoding the functional counterpart of MOM22. The MAS17 gene was
      found to be essential for the viability of yeast cells.

PMID- 7805892
TI  - cDNA and deduced amino acid sequence of human PK-120, a plasma kallikrein
      sensitive glycoprotein.
AB  - PK-120 is a substrate for plasma kallikrein (PK), recently purified from human
      plasma. Here we have established the cDNA sequence for human PK-120 mRNA. The
      deduced amino sequence of PK-120 revealed that it consists of 902 amino acid
      residues with a calculated mass of 116,423 Da. The putative cleavage sites by PK
      have been proposed, suggesting that PK-120 may be a precursor of a bioactive
      peptide. Most interestingly, PK-120 showed significant sequence identities to
      heavy chains (HCs) of the inter-alpha-trypsin inhibitor (ITI) superfamily.

PMID- 7805893
TI  - Expression of an active adenylate-forming domain of peptide synthetases
      corresponding to acyl-CoA-synthetases.
AB  - Peptide synthetases and acyl-CoA-synthetases form acyl adenylates which are
      transferred to CoA or enzyme-bound pantetheine. To verify the existence of an
      adenylate domain in peptide synthetases, a 60.8 kDa fragment of tyrocidine 1
      synthetase was constructed by a 1,629 bp deletion, expressed in Escherichia coli,
      and characterized. The truncated multienzyme activated phenylalanine and
      substrate analogues with comparable kinetics as the over-expressed synthetase, as
      judged by ATP-[32P]PP(i) exchange reaction. Thus the N-terminal domain resembling
      an acyl-CoA-synthetase is an autonomous structural element. This N-terminal
      domain is followed by a cofactor binding domain, resembling acyl carrier proteins
      involved in polyketide formation.

PMID- 7805894
TI  - Possible involvement of the 440 kDa isoform of ankyrinB in neuritogenesis in
      human neuroblastoma NB-1 cells.
AB  - Two isoforms of brain ankyrin, 440 kDa and 220 kDa ankyrinB, which are products
      of alternatively spliced pre-mRNA encoded by a single gene, are both expressed in
      human neuroblastoma NB-1 cells. Expression of the polypeptide and mRNA of the
      larger isoform increased upon induction of neurite outgrowth in NB-1 cells by
      dibutyryl cAMP, while those of the smaller isoform were unaffected. The expressed
      440 kDa ankyrinB was concentrated at the tip of growing neurites and was partly
      co-localized with GAP-43. These results suggest that 440 kDa ankyrinB is one of
      the neuronal growth-associated proteins and provides an interesting example of
      gene regulation by alternative splicing in neuronal cells.

PMID- 7805895
TI  - Prognostic assessment of ovarian reserve.
AB  - OBJECTIVE: To review the literature regarding diminished ovarian reserve, the
      screening techniques that are currently available, and their appropriate
      application in clinical practice. DATA RESOURCES: Directed Medline searches.
      RESULTS: Ovarian reserve screening identifies women with greatly diminished
      chances of achieving pregnancy. The screening techniques include the clomiphene
      citrate challenge test, basal day 3 FSH measurements, and the GnRH agonist
      stimulation test. All have been evaluated in assisted reproduction programs and
      the predictive values of an abnormal test for failing to conceive is very high.
      When abnormal, these tests allow physicians to counsel patients that their
      prognosis for conception is poor. Although the presence of a normal result does
      indicate better long-term chances for conception, an age-related decline in
      fecundity remains and patient age should still be considered when counseling
      patients with normal screening results. Clinicians are urged to validate the
      threshold values with the assay system used in their own laboratory before the
      application of these tests. CONCLUSION: The literature consistently demonstrates
      the value of diminished ovarian reserve screening.

PMID- 7805897
TI  - Coculture of embryos on homologous endometrial cells in patients with repeated
      failures of implantation.
AB  - OBJECTIVE: To evaluate the value of coculture of embryos on endometrial cells in
      patients with repeated failures of implantation. DESIGN: A retrospective
      comparison of pregnancy rates between IVF-ET with coculture and standard culture
      methods. PATIENTS: Ninety patients with repeated failures of transfer (range 4 to
      11) underwent IVF-ET for a variety of disorders. METHOD: Embryos were cocultured
      on homologous endometrial cells and transferred on day 4 after retrieval of
      oocytes. RESULTS: The overall pregnancy rate for these patients was 21% per
      transfer versus 8% in previous IVF-ET cycles. A higher percentage (28%) was
      obtained for women < 39 years of age or on transfer of at least one morula (32.5%
      pregnancy per transfer). CONCLUSION: Coculture of embryos on homologous
      endometrial cells is both safe and ethical. It appears to be a valuable approach
      for the selection of a good quality embryo before transfer. The technique should
      prove to be of benefit to patients with repeated failures of implantation and
      also may be of value for assessing the respective responsibility of endometrium
      and embryo in these repeated failures. However, the mechanisms underlying this
      improvement need to be determined to simplify the procedure.

PMID- 7805896
TI  - Vaginal color Doppler assessment of uterine artery impedance correlates with
      immunohistochemical markers of endometrial receptivity required for the
      implantation of an embryo.
AB  - OBJECTIVE: To investigate the correlation between uterine artery impedance with
      immunohistochemical histologic, and ultrasonographic markers of uterine
      receptivity. DESIGN: A prospective study of subfertile women undergoing a frozen
      embryo replacement cycle. SETTING: A tertiary infertility clinic. PATIENTS: The
      study was based on 86 patients who had failed to become pregnant during a
      standard IVF treatment cycle and who had at least two good quality embryos
      cryopreserved. INTERVENTIONS: All patients had pituitary desensitization with the
      GnRH analogue buserelin acetate, followed by E2 and P replacement therapy.
      Vaginal color Doppler images of both uterine arteries were obtained on days 7,
      14, and 21 of the first (trial) cycle. On day 21, an endometrial biopsy was taken
      for dating a 24-kd protein, placental protein 14, and E2 receptor assessment.
      After a menstrual bleed had been induced, administration of estrogen and P was
      reinstituted and embryos transferred to the uterus on the 3rd or 4th day of P
      administration. MAIN OUTCOME MEASURES: The mean pulsatility index of the left and
      right uterine arteries, a semiquantitative score of endometrial 24-kd protein,
      PP14, and E2 receptor assessment, endometrial histologic dating, and pregnancy
      outcome. RESULTS: Nineteen of 76 patients who had a successful ET became
      pregnant. The pulsatility index on day 14 of both the trial and ET cycles was
      significantly lower in those who achieved pregnancy as compared with those who
      did not conceive: 2.65 (range 1.3 to 3.4) versus 3.85 (1.8 to 6.8) and 2.85 (1.4
      to 3.6) versus 4.15 (2.1 to 6.8), respectively. There were significant
      correlations between pulsatility index and 24-kd protein, E2 receptor, and
      endometrial histology but not with PP14 and endometrial thickness. CONCLUSIONS:
      Uterine artery impedance has a significant correlation with biochemical markers
      of uterine receptivity and accurately predicts the probability of pregnancy in
      frozen embryo replacement cycles. It is a useful method for assessing uterine
      receptivity in assisted conception programs.

PMID- 7805899
TI  - Pitfalls in evaluating ovarian reserve.

PMID- 7805898
TI  - Effect of oxygen concentration on in vitro fertilization and embryo culture in
      the human and the mouse.
AB  - OBJECTIVE: To compare the effect of culturing oocytes, zygotes and embryos under
      low (5%) versus ambient (20%) oxygen conditions on human IVF results and on mouse
      blastocyst formation. DESIGN: A prospective, randomized study of 257 consecutive
      IVF treatment cycles in 186 couples undergoing oocyte retrieval for various
      reasons of infertility. Gametes and resulting embryos after IVF were alternately
      allocated to fertilization and culture either under a gas phase of 5% CO2/90%
      N2/5% O2, or 5% CO2/95% air (20% O2). Oocytes and embryos from randomly bred and
      hybrid mouse strains were randomly allocated to culture under either of the two
      gas phases. SETTING: A university hospital-based IVF-ET program. MAIN OUTCOME
      MEASURE: In the human, rates of fertilization, embryonic development at the time
      of embryo replacement (42 to 46 hours after insemination), pregnancy, and
      implantation were compared. In the mouse, the rates of blastocyst formation were
      compared. RESULTS: Clinical pregnancies occurred in 24.2% versus 19.4% of
      retrievals when culture took place under low oxygen versus ambient oxygen
      conditions. Fertilization, embryonic development, pregnancy, and implantation
      rates did not differ significantly between the groups. Slightly higher blastocyst
      rates occurred when mouse embryos from hybrid strains were cultured under low
      oxygen compared with culture under ambient oxygen conditions, whereas no such
      difference in blastocyst rates was found in randomly bred mouse embryos.
      CONCLUSIONS: This study failed to demonstrate any improvement in human IVF
      results associated with the use of a gas mixture of 5% CO2/90% N2/5% O2 during
      the first two days of development compared with the use of 5% CO2 in air.

PMID- 7805900
TI  - Controlled trial of high spermatic vein ligation for varicocele in infertile men.
AB  - OBJECTIVE: To determine whether high ligation is an effective treatment for
      infertile men with clinical varicocele. DESIGN: A randomized, controlled trial of
      high spermatic vein ligation was carried out. The patients were treated and
      observed for 3 years. SETTING: Infertility treatment clinic and andrology
      laboratory in a hospital. PATIENTS: Infertile men with abnormal semen analysis
      because of varicocele only. INTERVENTION: High ligation 1 year postrecruitment
      (group A) and at the beginning of the study (group B). RESULTS: Among the 20
      couples in group A, 2 pregnancies (10%) were achieved within the 1st year of
      observation period. During the year after high ligation, there were 8 pregnancies
      (44.4%), and during the 2nd year after high ligation, there were 4 more
      pregnancies (22.2%). In group B, 15 pregnancies (60%) occurred within the 1st
      year after operation. Three pregnancies (12%) and 1 pregnancy (4%) occurred
      during the 2nd and 3rd year, respectively. After operation in all patients of
      both groups, there was significant improvement in semen parameters, regardless of
      pregnancy occurrence. The difference in pregnancy rate (PR) between the operated
      group B and nonoperated group A during the 1st year of study was found to be
      highly significant. CONCLUSIONS: It is concluded that in a population of
      infertile men presenting varicocele as the only demonstrable factor of
      infertility, the varicocele is clearly associated with infertility and reduced
      testicular function, and its correction by ligation improves sperm parameters and
      fertility rate. Furthermore, the highest PR in both groups occurred during the
      1st year postoperation.

PMID- 7805902
TI  - Sperm morphology: assessing the agreement between the manual method (strict
      criteria) and the sperm morphology analyzer IVOS.
AB  - OBJECTIVES: To correlate the percentage normal morphology reported by different
      observers and a computerized method (IVOS; Hamilton-Thorne Research, Beverly, MA)
      on a slide-by-slide basis using strict criteria: [1] Experienced observer
      (T.F.K.) versus experienced observer (R.M.), [2] experienced observer (T.F.K.)
      versus sperm morphology analyzer (IVOS), and [3] repeatability of normal and
      abnormal cells (IVOS). DESIGN SETTING, PATIENTS: Slides from 30 different
      patients from the Tygerberg IVF program were selected randomly. Microscopic
      fields and sperm cells were chosen randomly and percent normal morphology was
      recorded (objectives 1 and 2). The same slides were used and a cell-by-cell
      repeatability was done as outlined (objective 3). RESULTS: Experiment 1
      (objective 1): there was no significant bias between T.F.K. and R.M. The limits
      of agreement were 8.6% and -7.3%. The SDs were not significantly different (P =
      0.1283). The Spearman correlation coefficient between readers was 0.83.
      Experiment 2 (objective 2): the same findings were reported but the limits of
      agreement were 12.1% and -15.5%. The Spearman correlation coefficient was 0.85.
      The limits of agreement was tighter below 20% normal forms (+8.4 and -6.6).
      Experiment 3 (objective 3) (repeatability): 255 cells were analyzed three times
      in succession. Estimating pairwise agreement, the kappa statistic for the pairs
      are 0.85, 0.80, and 0.85, respectively, which compares favorably with the second
      canonical moment of 0.8329 (kappa = 0.83). DISCUSSION: The computer's ability to
      classify normal morphology per slide is promising. Below 20% normal forms, the
      limit of agreement is tight. Because of the 6% higher reading compared with the
      manual method, different thresholds possibly will be developed to identify
      subfertile from fertile patients. The computer gives excellent repeatability of
      normal and abnormal cells. Based on results obtained, this system can be of
      clinical value both in IVF units and andrology laboratories but more clinical
      data is required in this field.

PMID- 7805901
TI  - Factors in nonuniform induction of azoospermia by testosterone enanthate in
      normal men. World Health Organization Task Force on Methods for the Regulation of
      Male Fertility.
AB  - OBJECTIVE: To identify factors differentiating men becoming azoospermic from
      those remaining oligozoospermic within 6 months of T treatment. DESIGN:
      Prospective, open, noncomparative contraceptive efficacy study. SETTING:
      International multicenter study of 271 men in 10 centers in seven countries.
      PATIENTS: Data from 157 achieving azoospermia and 68 remaining oligozoospermic
      after 6 months of treatment were analyzed. The remaining 46 men were excluded as
      having unclassifiable suppression status due to discontinuation before completion
      of suppression. INTERVENTIONS: Weekly IM injections of 200 mg T enanthate. MAIN
      OUTCOME MEASURES: Anthropometric, seminal, hormonal, and biochemical data
      obtained before, during, and after treatment as potential predictors of
      consistent azoospermia. RESULTS: Azoospermic men had [1] faster rates of fall in
      sperm output and, after a delay of 75 +/- 4 days (mean +/- SE) for sperm to
      reappear in the ejaculate, exhibited a faster rate of recovery of sperm output;
      [2] higher pretreatment levels of FSH (mean +/- SE; 3.7 +/- 0.3 versus 2.7 +/-
      0.4 mIU/mL [conversion factor to SI units, 1.00]); and [3] (if treated for > 15
      months) a prolonged after treatment rebound in gonadotropins compared with
      nonazoospermic men. There were no other differences in pretreatment variables or
      plasma T levels and changes in androgen-sensitive markers during treatment. None
      of the variables explained the higher rates of azoospermia among men in Chinese
      (91%, n = 3) compared with non-Chinese centers (60%, n = 7). CONCLUSION:
      Nonuniformity of T-induced azoospermia among healthy fertile men is not due to
      anthropometric or ethnic differences, to variations in androgen effects, or to
      poor compliance with treatment. The heterogeneity in individual susceptibility to
      T-induced azoospermia is most consistent with quantitative differences in the
      hormonal regulation of spermatogenesis and is likely to be evident with other
      hormonal methods for male contraception.

PMID- 7805903
TI  - Antibiotic therapy and leukocytospermia: a prospective, randomized, controlled
      study.
AB  - OBJECTIVE: To determine the efficacy of common antibiotic therapies for treatment
      of leukocytospermia of unknown etiology. DESIGN: Prospective, randomized,
      controlled clinical study. SETTING: Fertility and Endocrinology Unit at Brigham
      and Women's Hospital, Boston, Massachusetts. PATIENTS: One thousand seven hundred
      ten male partners in infertile couples attending the Fertility and Endocrinology
      Unit. INTERVENTIONS: Concentrations of seminal peroxidase-positive granulocytes
      were determined during all routine semen analyses performed over a 30-month
      period. Of 119 men found to have leukocytospermia (> 10(6) granulocytes/mL semen)
      on first visit, 54 agreed to be randomized into one of three groups, and 41
      patients completed the study. Group I (n = 13) and their wives received a 14-day
      course of oral doxycycline, 100 mg twice per day. Group II (n = 11) and their
      wives received a 14-day course of oral trimethoprim 160 mg-sulfamethoxazole 800
      mg twice per day. Group III (n = 17) and their wives received no therapy. Four
      weeks after randomization, repeat semen analyses and granulocyte quantitations
      were done. RESULTS: Neither of the antibiotic regimens resulted in a
      significantly higher rate of resolution of leukocytospermia over that seen in the
      control group. CONCLUSIONS: There is a high rate of spontaneous resolution of
      leukocytospermia after one positive test. Antibiotics are no more beneficial than
      no therapy for treatment of this condition.

PMID- 7805904
TI  - Ultrastructural changes in sperm with improved fertilizability after treatment
      with egg yolk.
AB  - OBJECTIVES: To determine the existence of differences in the ultrastructural
      parameters between the medium-washed sperm samples of the affected and
      nonaffected egg yolk (EY) groups and to verify whether ultrastructural changes
      occur in the EY-affected spermatozoa after EY preincubation. SETTING: The study
      was performed in the Laboratory of the IVF Unit, Serlin Maternity Hospital, and
      the Laboratory of Male Fertility, Bar-Ilan University, Ramat Gan, Israel.
      PATIENTS: The positive group included 12 males who underwent 1.9 IVF cycles with
      0% fertilization rate that increased to 68% after EY treatment. The negative
      group included 11 males with 1.2% fertilization rate in 1.1 IVF cycles with no
      improvement after preincubation of spermatozoa in EY. RESULTS: Compared with the
      laboratory standard, patients of both groups exhibited a lower normalcy of the
      head sperm cell subcellular organelles. With EY treatment, the positive group
      exhibited a decrease in the frequency of some sperm head organelle specific
      malformations. CONCLUSIONS: Fertilization capacity of mature spermatozoa might be
      reduced because of an excess of acrosome malformations, postacrosomal lamina, and
      chromatin caused by in vitro sperm manipulations. The manipulation effect may be
      avoided by EY treatment.

PMID- 7805905
TI  - Spontaneous resolution of ectopic tubal pregnancy: natural history.
AB  - OBJECTIVE: To determine the characteristics and long-term outcome of women
      succeeding or failing expectant management of ectopic pregnancy (EP). DESIGN:
      Prospective, defined protocol. SETTING: University-affiliated gynecology
      department. PATIENTS: We used a protocol that selected women with laparoscopic
      confirmed ectopic tubal pregnancy and declining plasma hCG values. Over a 5-year
      period, 60 women representing 20.1% of EPs fulfilled the inclusion criteria.
      Women were followed with serial hCG testing and transvaginal ultrasound. MAIN
      OUTCOME MEASURE: Success or failure of expectant management. RESULTS: Expectant
      management was successful in 28 (47.7%) of the patients. Thirty-two (53.3%)
      failed expectant management, and a treatment procedure was required. There was no
      difference in the resultant ipsilateral tubal patency or 1-year fertility rates
      of those women succeeding or failing expectant management. Analysis showed that
      in the face of declining values and with a starting hCG > 2,000 mIU/mL
      (conversion to SI unit, 1.00), 93.3% failed expectant management, whereas < 2,000
      mIU/mL, 60.0% succeeded. CONCLUSION: We conclude that expectant management should
      be offered as a treatment option only in those women fulfilling the criteria for
      a good prognosis.

PMID- 7805906
TI  - Alleviation of acrosome reaction prematurity by sperm treatment with egg yolk.
AB  - OBJECTIVE: To examine the effects of egg yolk on the spontaneous and ionophore
      induced acrosome reaction (AR) and sperm-zona pellucida (ZP) binding in
      spermatozoa from patients with AR prematurity. DESIGN: Prospective analysis.
      SETTING: Private hospital, public research center, and a university-based
      laboratory. PATIENTS: In vitro fertilization patients selected on the basis of
      previous AR testing. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Frequency of the
      AR, number of ZP-bound spermatozoa. RESULTS: The pretreatment of spermatozoa with
      egg yolk decreased the frequency of AR occurring spontaneously during subsequent
      sperm incubation in capacitating medium but did not modify the sperm response to
      ionophore. The egg yolk-treated spermatozoa also showed a greater capacity of
      binding the ZP than their untreated counterparts. CONCLUSIONS: The pretreatment
      of spermatozoa with egg yolk alleviates the sperm-ZP binding deficiency resulting
      from premature initiation of the AR and may be helpful in IVF with patients
      showing this anomaly.

PMID- 7805907
TI  - Human sperm motility-enhancing agents have detrimental effects on mouse oocytes
      and embryos.
AB  - OBJECTIVES: To test the artificial activating properties of the human sperm
      motility-enhancing agents pentoxifylline, caffeine, 2-deoxyadenosine, and cyclic
      adenosine 3':5' monophosphate (cAMP) on mouse oocytes and determine if the agents
      exhibit an inhibitory effect on in vitro development of mouse embryos. DESIGN: CD
      1 mouse oocytes were exposed to 1, 2.5, 5, or 10 mM pentoxifylline, caffeine, 2
      deoxyadenosine, or cAMP for 10, 30, or 60 minutes and their activation and
      development was scored over 96 hours of culture. A 10% ethanol solution and aging
      unstimulated oocytes served as controls. Pronuclear embryos from CD-1, CF-1, and
      B6C3 F1 hybrid mice were cultured in 0.16, 0.33, 0.66, 1.25, 2.5, 5.0, or 10 mM
      of pentoxifylline, caffeine, 2-deoxyadenosine, or cAMP and development was scored
      over 96 hours of culture. RESULTS: Exposure to pentoxifylline, caffeine, and 2
      deoxyadenosine, but not cAMP, artificially activated mouse oocytes in a
      concentration- and exposure time-dependent manner. The level of activation was
      significantly greater than that associated with oocyte aging but less than
      ethanol-induced activation. Agent-activated oocytes had limited developmental
      capacity compared with the ethanol-activated oocytes. Pentoxifylline and 2
      deoxyadenosine were more toxic than caffeine, especially at the higher
      concentrations and after prolonged exposure. All of the agents affected embryo
      development in a dose-dependent manner with developmental inhibition and
      embryotoxicity that was often not evident until after one to three cell cycles.
      CONCLUSIONS: Pentoxifylline, caffeine, 2-deoxyadenosine, and cAMP have adverse
      effects on mouse oocytes or embryos at concentrations commonly used to activate
      sperm in human IVF. Therefore, care should be taken to minimize the exposure of
      human oocytes and embryos to these agents until their direct effects have been
      investigated more fully.

PMID- 7805908
TI  - The ovarian action of interleukin-1 is receptor mediated: reversal by a naturally
      occurring interleukin-1 receptor antagonist.
AB  - OBJECTIVE: To address indirectly the possibility that the ovarian action(s) of
      interleukin (IL)-1 are receptor mediated and to re-examine the recently reported
      proposition that the naturally occurring IL-1 receptor antagonist (IL-1ra) may in
      fact act in the capacity of mixed IL-1 receptor agonist/antagonist. DESIGN: In
      vitro treatment of isolated granulosa cell (GC) and whole ovarian dispersates of
      rat origin. RESULTS: Treatment of GC from immature rats with increasing
      concentrations of IL-1ra (10 to 5,000 ng/mL) proved without effect on either the
      basal or FSH (100 ng/mL)-supported accumulation of P. Likewise, cellular
      viability (as assessed by conversion of 3-[4,5-dimethylthiazol-2-yl]-2-5
      diphenyltetrazolium bromide to spectrophotometrically detectable formazan)
      remained unaltered. However, the concomitant addition of increasing
      concentrations of IL-1ra (10 to 5,000 ng/mL) yielded dose-dependent reversal of
      the 10 ng/mL IL-1 beta-mediated inhibition of the FSH-supported accumulation of
      P. Similarly, the ability of IL-1 beta to exert a dose-dependent (0 to 30 ng/mL)
      anti-gonadotropic effect was attenuated progressively given the concurrent
      presence of increasing concentrations (1,000 and 5,000 ng/mL) of IL-1ra. Although
      treatment of whole ovarian dispersates with 10 ng/mL IL-1 beta resulted in a 5.4
      fold increase in the accumulation of prostaglandin (PG)E2, this effect too was
      all but eliminated after the concomitant addition of 5 micrograms/mL IL-1ra.
      CONCLUSIONS: These observations support the nontoxic nature of IL-1ra, confirm
      its lack of agonistic activity, validate its utility as an experimental probe,
      and suggest that neither the basal nor the FSH-stimulated accumulation of P are
      subject to regulation by endogenously produced GC-derived IL-1-like activity.
      Moreover, these observations suggest that the ability of IL-1 beta to inhibit the
      gonadotropin-supported accumulation of P and to increase PGE2 accumulation is
      receptor-mediated.

PMID- 7805909
TI  - High fertilization rate with intracytoplasmic sperm injection in mosaic
      Klinefelter's syndrome.
AB  - With the introduction of intracytoplasmic sperm injection (ICSI) as a practical
      successful treatment for male infertility, we are able to offer the procedure to
      a group of patients who probably could never father a child of their own. From a
      patient with mosaic Klinefelter's syndrome, sufficient motile sperm for
      intracytoplasmic sperm injection were obtained from a fresh ejaculate estimated
      to contain < 100 motile sperm. In the first IVF-ICSI attempt, out of seven
      oocytes that were collected from the wife, four were mature and were injected by
      ICSI. Fertilization occurred in all four oocytes but only one cleaved and was
      transferred to the uterus. Pregnancy test was negative 16 days after ET. In the
      second treatment cycle four out of eight oocytes were selected for ICSI. All four
      fertilized, three cleaved at the right time, and two were transferred into the
      wife's uterus. One embryo was frozen. Pregnancy test 16 days after ET was
      negative. The high fertilization rate achieved in this case indicates the
      potential of ICSI to treat extreme male infertility. Its use offers hope to those
      patients with conditions previously considered to be untreatable.

PMID- 7805910
TI  - Effect of freezing on the relative escape force of sperm as measured by a laser
      optical trap.
AB  - OBJECTIVE: To determine the possible effect of freezing on sperm escape force as
      measured by laser trap. DESIGN: Controlled clinical study. SETTING: Normal
      volunteers, academic setting. PATIENTS: Normal, healthy volunteers. INTERVENTION:
      Sperm selection, freezing and thawing. Measurement of relative (sperm) escape
      force before and after freezing. MAIN OUTCOME MEASURE: Comparison of escape force
      as a measurement of freezing effects. RESULTS: Wide individual variations noted,
      with some individuals showing significant increases or decreases. The relative
      escape force in fresh (76.1 +/- 31.1 mW) and in frozen-thawed samples (75.6 +/-
      40.0 mW) were similar. CONCLUSION: Freezing does not affect the relative escape
      force of normal sperm. Any possible detrimental effect of freezing on sperm may
      be related to other sperm functions.

PMID- 7805912
TI  - Cyclical breast pain and swelling in relation to differing patterns of
      suppression of ovarian activity with the luteinizing hormone-releasing hormone
      analogue buserelin acetate: case report.
AB  - The presenting complaints of an amenorrhoeic (after hysterectomy with ovarian
      preservation) woman were cyclical breast pain and swelling. These showed
      synchronicity with fluctuations in E2 levels. Both ovarian activity and symptoms
      initially responded to (after lag periods of approximately 40 days) daily SC
      injections of the LH-RH analogue buserelin acetate. After a break in treatment,
      the interval between reinitiation of therapy and suppression of E2 levels was
      prolonged markedly, ovarian function being apparently resistant even to very
      large doses of the analogue.

PMID- 7805911
TI  - Molecular biologic analyses of tetragametic chimerism in a true hermaphrodite
      with 46,XX/46,XY.
AB  - OBJECTIVE: To investigate the mechanism of the formation of a tetragametic
      chimera with true hermaphroditism (46,XX/46,XY). DESIGN: Molecular biologic
      analyses. SETTING: Outpatient clinic and laboratories of a university hospital.
      SUBJECTS: A true hermaphrodite with 46,XX/46,XY and the parents. MAIN OUTCOME
      ANALYSIS: Restriction fragment length polymorphism (RFLP) of the pseudoautosomal
      region on sex chromosomes. RESULTS: Whereas a normal diploid individual showed
      two bands, the true hermaphrodite showed four bands in the RFLP analyses.
      Evaluation of the molecular weights of the bands revealed two of them to be of
      maternal origin and the other two to be of paternal origin. CONCLUSION: The two
      cell lineages composing the true hermaphrodite are heterogeneous because those
      originated from the fertilization of two genetically different maternal haploid
      cells by two different spermatozoa.

PMID- 7805913
TI  - An incidental diagnosis of well-differentiated papillary mesothelioma in a woman
      operated on for recurrent endometriosis.
AB  - The case presented involves a report of severe endometriosis with recurrent
      disabling dysmenorrhea associated with well-differentiated mesothelioma. Although
      the course of mesotheliomas is predominantly benign, the diversity of lesions,
      variable behavior, and resemblance, and association with endometriosis warrant
      thorough diagnostic investigation. Multiple biopsies and differential diagnoses
      are recommended in cases of peritoneal endometriosis.

PMID- 7805914
TI  - Endometriosis and infertility: the role of exogenous lipid peroxides in the
      peritoneal fluid.
AB  - OBJECTIVE: To determine if lipid peroxides were raised in the pelvic peritoneal
      fluid of patients with endometriosis. DESIGN: Control study involving patients
      with and without endometriosis. METHODS: The lipid peroxide (malondialdehyde)
      levels in the pelvic PF of 12 patients with moderate-to severe endometriosis, 15
      patients with minimal-mild endometriosis and 13 patients with normal pelvises
      were compared. RESULTS: The level of lipid peroxides were not affected by the
      presence nor the severity of endometriosis. CONCLUSION: Accelerated lipid
      peroxidation does not appear to play a role in the causal relationship between
      endometriosis and infertility.

PMID- 7805915
TI  - Limited role for intratubal methotrexate treatment of ectopic pregnancy.
AB  - OBJECTIVE: To test the effectiveness of laparoscopic intratubal methotrexate
      (MTX) injection or salpingostomy in the treatment of ectopic pregnancy (EP).
      DESIGN: Prospective predefined protocol. SETTING: Department of Obstetrics and
      Gynecology of a university-affiliated hospital. PATIENTS AND INTERVENTIONS:
      Between January 1988 and December 1993, we treated 342 women with EP, of which 99
      were treated by either laparoscopic salpingostomy (n = 55) or intratubal MTX
      injection (n = 44). MAIN OUTCOME MEASURES: The success and failure rates were
      calculated for each treatment protocol. Also analyzed were subsequent tubal
      patency and fertility rates. RESULTS: Salpingostomy was successful in 51 of 55
      patients (92.7%), whereas intratubal MTX injection was successful in only 27 of
      44 women (61.4%). Methotrexate injection particularly was unsuccessful if the
      initial hCG was > 2,000 mIU/mL (conversion factor to SI unit, 1.00) or the size
      of the tubal mass was > 2.0 cm as measured during laparoscopy. There was no
      difference in the subsequent tubal patency rates of fertility rates between women
      undergoing MTX injection or salpingostomy. CONCLUSIONS: These results suggest
      that salpingostomy is effective in the treatment of EP. Methotrexate injection
      failed in more patients despite preferential selection criteria, suggesting that
      its use should be limited to the subgroup of women with initial hCG < 2,000
      mIU/mL and size at laparoscopy < 2.0 cm.

PMID- 7805917
TI  - Appropriate management of interstitial pregnancies?

PMID- 7805918
TI  - Value of percutaneous epididymal sperm aspiration?

PMID- 7805916
TI  - Effect of peritoneal fluid, follicular fluid, and their volumetric mixture on
      acrosomal reactivity in vitro.
AB  - OBJECTIVE: To determine the effects of peritoneal and follicular fluids (PFs,
      FFs) on sperm acrosomal reaction (AR). DESIGN: Prospective, randomized study.
      SETTING: Three hospital-based infertility units. PATIENTS: Twenty-three women
      participating in GIFT programs; 23 men participating in AIH programs.
      INTERVENTIONS: Hormonal stimulation after buserelin desensitation; laparoscopy 36
      hrs after hCG injection. MAIN OUTCOME MEASURE: Percentage of acrosomally-reacted
      sperm. RESULTS: Compared with Earle's medium (control), moderate but significant
      increases of ARs were observed as function 1) of the relative content of FF in
      the incubation medium and 2) as function of time (these increases were constantly
      lower than those registered for the respective positive control, i.e. 2x
      frozen/thawed sperm). In contrast, when PF alone was present in the incubation
      medium, no such effects on AR were registered. CONCLUSIONS: FF and mixtures of PF
      and FF--but not PF alone--seem to induce some rapid and time-dependent processes
      which finally lead to an AR. Therefore, and independently on the infertility
      cause (tubal, male-dependent, unexplained infertility), PF seems able to exert
      effects on sperm motility (Revelli et al., Fertil. Steril 57, 654-60 [1992])
      while maintaining an unreacted sperm status.

PMID- 7805919
TI  - Ultrasound-guided injection of methotrexate versus laparoscopic salpingotomy in
      ectopic pregnancy.
AB  - OBJECTIVE: To compare local injection of methotrexate (MTX) under sonographic
      control to laparoscopic salpingotomy for conservative management of ectopic
      pregnancy (EP). DESIGN: Prospective randomized study. PATIENTS: Forty patients
      were randomized into two groups using a random number table. Inclusion criteria
      were an EP visualized by ultrasound with a pretherapeutic score < or = 13 as
      assessed by six criteria graded from 1 to 3: gestational age, hCG level, P level,
      abdominal pain, volume of the hemoperitoneum, and diameter of the hematosalpinx.
      INTERVENTIONS: Group 1 patients injected transvaginally with 1 mg/kg MTX into the
      EP without anesthesia versus group 2 patients undergoing laparoscopic
      salpingotomy. MAIN OUTCOME MEASURES: Postoperative hospital stay, decrease of hCG
      levels, success rate. RESULTS: The success rates, defined by hCG levels returned
      to normal (< 10 mIU/mL [conversion factor to SI units, 1.00]), were 19 of 20 in
      both groups. Medical treatment was associated significantly with shorter
      postoperative stay (24 versus 46 hours) and a higher initial hCG level. Human
      chorionic gonadotropin returned to normal more quickly after laparoscopic
      treatment (14 versus 28 days). CONCLUSIONS: In selected cases of EP with a
      pretherapeutic score < or = 13, MTX treatment appeared to be as safe and
      efficient as was conservative treatment by laparoscopy.

PMID- 7805920
TI  - Luteal phase defects and ectopic pregnancy.
AB  - OBJECTIVE: To determine whether luteal phase defect (LPD) may be an etiologic
      factor in ectopic pregnancy (EP). DESIGN: All patients who were seen over a 6
      year period with the chief complaint of infertility underwent an extensive
      infertility workup and were followed prospectively. The diagnoses of the causes
      of infertility were assigned retrospectively. SETTING: Two hospital-based
      tertiary care reproductive endocrine-infertility units. PATIENTS: A total of
      1,077 infertility patients were evaluated. Of the 633 who became pregnant, the
      infertility had been due to LPD in 51 and to anovulation in 210. MAIN OUTCOME
      MEASURES: All the infertility patients who became pregnant were followed to
      determine whether they miscarried, developed an EP, or had a viable birth. The
      incidence of EP and miscarriage in the patients whose infertility was found to be
      due to LPD were compared with a control group in whom the infertility was due to
      anovulation. RESULTS: The EP rate in the patients with LPD was significantly
      higher than in a control group whose infertility was due to anovulation (6 of 51
      pregnancies versus 6 of 210 pregnancies, respectively). The spontaneous abortion
      rate in LPD cases also was highly significantly greater than in the control group
      (19 of 51 pregnancies versus 12 of 210 pregnancies, respectively). The EP and
      spontaneous abortion rates also were higher in patients with LPD who were
      untreated than in those who were treated. CONCLUSIONS: This study suggests that
      there is a significantly increased incidence of tubal EP in patients with LPD and
      that when patients with LPD become pregnant early ultrasound should be performed
      to rule out EP. The study also indicated that spontaneous abortion occurs in a
      significantly high percentage of LPD cases.

PMID- 7805921
TI  - Epidemiology of endometriosis in infertile women.
AB  - OBJECTIVE: To assess the epidemiological factors linked to endometriosis in
      infertile women. SETTING: Academic tertiary hospital. DESIGN: Case-control study.
      PATIENTS: One hundred seventy-four infertile women with endometriosis and 174
      infertile women without endometriosis, all of them studied by laparoscopy.
      RESULTS: Women with endometriosis and infertility had a higher frequency of
      cycles < or = 27 days (26.4% versus 16.7%). A trend to a protective effect of
      smoking was detected. Social class, reproductive history, infertility history,
      previous abortions, age, family history, age at menarche, and duration of
      menstrual flow were similar in both groups. CONCLUSION: Cycles < or = 27 days was
      the only risk factor that seemed to be associated to endometriosis in infertile
      patients. However, predictive values were low. A trend to a protective effect of
      smoking was detected.

PMID- 7805922
TI  - Association of Chlamydia trachomatis immunoglobulin gamma titers with dystrophic
      peritoneal calcification, psammoma bodies, adhesions, and hydrosalpinges.
AB  - OBJECTIVE: To correlate Chlamydia trachomatis immunoglobulin gamma (IgG) titers
      with psammoma bodies, dystrophic peritoneal calcification, degree of
      calcification, adhesions, and hydrosalpinges. DESIGN: This is a prospective
      single-blinded histologic analysis of tissue and retrospective analysis of
      historical laboratory and clinical variables. SETTING: Tertiary hospital and
      private practice patient charts. PATIENTS: Sixty consecutive patients with C.
      trachomatis IgG titers reported on the coding sheets of a previous study for
      endometriosis. MAIN OUTCOME MEASURES: The histologic slides were reviewed in a
      blinded fashion for calcification. Previously used data sheets were reviewed for
      C. trachomatis IgG titers. Historical data, adhesion scores, hystrosalpingogram
      findings, and laparoscopic findings were obtained from charts. RESULTS:
      Dystrophic calcification, psammoma bodies, moderate-to-severe dystrophic
      calcification and hydrosalpinges were associated with positive C. trachomatis IgG
      titers. CONCLUSION: This study suggests relationship of C. trachomatis with
      dystrophic calcification, psammoma bodies, adhesions, and hydrosalpinges. This
      relationship suggests that C. trachomatis IgG titers can be used as a marker to
      help determine those infertility patients who might best benefit from
      hysterosalpingogram or laparoscopy and in clinical studies of endometriosis,
      infertility, pain, or ovarian cancer. However, there is no current data to
      suggest a need for therapy on the basis of a positive C. trachomatis IgG titer or
      of dystrophic peritoneal calcification.

PMID- 7805923
TI  - Plasminogen activators in ectopic and uterine endometrium.
AB  - OBJECTIVE: To investigate the expression of the plasminogen activator (PA)
      plasmin system components in ectopic endometrium and in uterine endometrium from
      women with and without endometriosis. DESIGN: Plasminogen, PAs (urokinase and
      tissue plasminogen activator), and PA inhibitors (1 and 2) were detected by
      immunohistochemistry using a alkaline phosphatase staining method. RESULTS: No
      differences in staining were found between uterine endometrium of women with
      endometriosis and women without endometriosis with any of the antibodies used.
      However, we did find differences between uterine and ectopic endometrium.
      Although the expression of the components of the PA-plasmin system reflected the
      cyclic changes in the hormonal levels in uterine endometrium, ectopic endometrium
      maintained a very high level of plasminogen and urokinase in every sample. We
      were unable to detect the presence of PA inhibitors in either uterine or ectopic
      endometrium. CONCLUSIONS: There is no evidence that uterine endometrium from
      women with endometriosis is originally more able to implant than that of women
      without the disease because of an increase in their PA expression. The high
      levels of urokinase and plasminogen in ectopic endometrium may reflect a more
      invasive nature of the endometriotic implants in the peritoneal cavity.

PMID- 7805924
TI  - Expression of messenger ribonucleic acid for gonadal steroid receptors in the
      human pelvic peritoneum.
AB  - OBJECTIVE: To investigate the expression of messenger RNA (mRNA) for gonadal
      steroid hormone receptors in the human pelvic peritoneum. DESIGN: Analysis of
      estrogen receptor (ER), progesterone receptor (PR), and androgen receptor (AR)
      mRNA expressions in the pelvic peritoneum was carried out using the quantitative
      reverse transcription-polymerase chain reaction (PCR) method. SETTING: Department
      of Gynecology and Obstetrics, Kyoto University Hospital, Kyoto, Japan. PATIENTS:
      Pelvic peritoneal tissues from patients with (n = 10) and without (n = 10)
      endometriosis who had undergone gynecological surgery were studied. RESULTS:
      Estrogen receptor, PR, and AR mRNAs were detected in all pelvic peritoneal
      samples analyzed. In the pelvic peritoneum of patients without endometriosis, ER
      mRNA levels were significantly lower in the luteal phase than in the follicular
      phase. This cyclic profile of ER mRNA expression was not observed in the pelvic
      peritoneum of patients with endometriosis. During the follicular phase, ER mRNA
      levels in the pelvic peritoneum of patients with endometriosis were significantly
      lower than those of patients with endometriosis. Neither PR nor AR mRNA levels in
      the pelvic peritoneum of either patient group showed significant cyclic
      variations throughout the menstrual cycle. A comparison of PR and AR mRNA levels
      in the pelvic peritoneum of the endometriosis and the nonendometriosis groups
      revealed no significant differences. CONCLUSIONS: These data indicate a decrease
      in ER gene expression in the pelvic peritoneum of patients with endometriosis
      during the follicular phase. This suggests that the possible responsiveness of
      peritoneal cells to estrogen may be related to the occurrence and/or development
      of endometriosis.

PMID- 7805925
TI  - Ethnic differences in insulin and glucose response to glucose between white and
      Indian women with polycystic ovary syndrome.
AB  - OBJECTIVE: To examine different patterns of glucose and insulin secretion in
      women (of both Indian and white ethnic backgrounds) with polycystic ovary
      syndrome (PCOS). DESIGN: A 75-g oral glucose tolerance test was performed in 11
      subjects from each group. SETTING: Reproductive Medicine and Gynecological
      Clinics from The Queen Elizabeth Hospital, Woodville, South Australia, and King
      Edward the VIIIth Hospital, Durban, South Africa. PATIENTS: Couples were grouped
      as follows: Indian nonobese and obese PCOS, Indian nonobese and obese reference
      subjects, white nonobese and obese PCOS, white nonobese and obese reference
      subjects. MAIN OUTCOME MEASURE: Insulin and glucose in plasma after oral glucose
      testing. RESULTS: Indian PCOS and nonobese reference subjects had higher insulin
      responses than whites. The ethnic difference was less pronounced in obese women.
      There were no ethnic differences in glucose response. CONCLUSION: This study
      demonstrates that the ethnic background of subjects with PCOS needs to be
      considered in studies on the metabolic parameters in this condition.

PMID- 7805926
TI  - Antisperm antibodies in infertile women: subclass distribution of immunoglobulin
      (Ig) A antibodies and removal of IgA sperm-bound antibodies with a specific IgA1
      protease.
AB  - OBJECTIVE: To determine the immunoglobulin (Ig) A subclass distribution of
      antibodies in the serum and cervical mucus (CM) of infertile women and to
      evaluate the effect of an IgA1 protease on the removal of sperm-bound antibodies.
      METHODS: Twenty infertile women with antisperm antibodies in serum (n = 10) or in
      CM (n = 10) were recruited for this study. Monoclonal antibodies to human IgA1
      and IgA2 were conjugated to immunobeads and the IgA subclass distribution of
      antisperm antibodies was determined for positive serum and CM samples. The effect
      of an IgA1 protease (isolated from Neisseria meningitidis strain HF13) on sperm
      bound antibodies was evaluated by immunobead binding. RESULTS: In serum, IgA1
      subclass antisperm antibodies predominated (89%) when compared to IgA2 (11%). In
      CM IgA1 accounted for 62% and IgA2 accounted for 38% of the total IgA antisperm
      antibodies. Enzyme treatment was able to reduce dramatically the amount of serum
      IgA antibodies bound to sperm from 88% to 10%. Similarly, a significant reduction
      in CM antisperm antibodies was observed after enzymatic treatment with no loss in
      sperm motility. CONCLUSION: Cervical mucus antisperm antibodies have a higher
      proportion of IgA2 subclass suggesting a local production of IgA. Specific IgA1
      protease treatment is capable of reducing the amount of immunobead-detectable IgA
      on sperm. Hamster sperm penetration assays are ongoing to determine if this
      treatment might improve sperm penetration rates with antibody positive sperm.

PMID- 7805927
TI  - In vitro fertilization and oocyte donation in women 45 years of age and older.
AB  - OBJECTIVE: To assess the reproductive potential in women > or = 45 years of age.
      DESIGN: Retrospective analysis. SETTING: In vitro fertilization-embryo transfer
      unit, standard IVF and oocyte donation programs. PATIENTS: One hundred twenty
      seven patients > or = 45 years old who applied for treatment of infertility.
      INTERVENTION: Thirty-one patients underwent 52 treatment cycles in standard IVF.
      Ninety-six patients underwent 220 oocyte donation cycles. RESULTS: Of the 52
      standard IVF cycles, oocytes were retrieved successfully in only 32. Of these,
      fertilization and ET were performed in 21 cycles. None of these treatment cycles
      resulted in a clinical pregnancy. Of the 220 oocyte donation cycles,
      fertilization and ET were accomplished in 189 cycles. These resulted in 33 (17.5%
      per transfer) clinical pregnancies. CONCLUSIONS: These results suggest that
      oocyte donation may extend the reproductive potential in women > or = 45 years
      old when little hope is offered by standard IVF.

PMID- 7805928
TI  - Clinical assessment of recombinant human follicle-stimulating hormone in
      stimulating ovarian follicular development before in vitro fertilization.
      Recombinant Human FSH Study Group.
AB  - OBJECTIVE: To compare the efficacy and the safety of recombinant human FSH (hFSH)
      with urinary hFSH for stimulating follicular development in women undergoing IVF
      ET. DESIGN: Multicenter, prospective, randomized, open, parallel group, clinical
      study. SETTING: Eight European academic IVF units and one private IVF unit.
      PATIENTS: Infertile female patients aged 18 to 38 years suffering from tubal
      disease, mild endometriosis, or unexplained infertility. INTERVENTIONS:
      Pretreatment with buserelin acetate was followed by recombinant or urinary hFSH
      treatment started at an initial dose of 225 IU FSH/d. Dose adjustment was allowed
      after 5 days of FSH. After administration of hCG, a standard IVF-ET procedure was
      performed. MAIN OUTCOME MEASURES: Follicular development, oocyte retrieval,
      fertilized oocytes, duration and dose of FSH, and pregnancy. The hypothesis
      formulated before the study was that no difference was expected between the two
      FSH preparations. RESULTS: Sixty patients were treated with recombinant hFSH and
      63 with urinary hFSH. The mean number (+/- SD) of growing follicles (mean
      diameter > 10 mm) was 10.3 +/- 4.9 and 11.2 +/- 5.2, of follicles (mean diameter
      > 14 mm) was 7.8 +/- 3.6 and 9.2 +/- 4.5, of retrieved oocytes was 9.3 +/- 5.0
      and 10.7 +/- 5.3, and of fertilized oocytes was 5.6 +/- 3.8 and 6.5 +/- 4.3, for
      recombinant and urinary hFSH, respectively. The duration of FSH treatment was 9.9
      +/- 2.3 and 9.4 +/- 1.8 days and the average total dose was 2270 +/- 714 and 2095
      +/- 591 IU of FSH, for recombinant and urinary hFSH, respectively. Thirteen
      pregnancies were recorded in the recombinant hFSH group and 11 in the urinary
      hFSH group. Nine patients delivered 13 live infants in the recombinant hFSH group
      and eight delivered 13 live infants in the urinary hFSH group. In terms of
      safety, no difference was recorded between the groups and no anti-FSH antibodies
      were found in any of the patients. CONCLUSIONS: This clinical study shows that
      recombinant hFSH is as safe and effective as urinary hFSH in stimulating ovarian
      follicular development.

PMID- 7805929
TI  - High implantation rate and consequently high pregnancy rate by in vitro
      fertilization-embryo transfer treatment in infertile women with antisperm
      antibody.
AB  - OBJECTIVE: To examine the effect of antisperm immunity on postfertilization
      steps, such as implantation of embryos and fetal growth in IVF-ET treatment of
      women with sperm-immobilizing antibodies. DESIGN: Retrospective analysis of
      clinical laboratory data. SETTING: The IVF-ET program of the Department of
      Obstetrics and Gynecology. The University of Tokushima, School of Medicine.
      PATIENTS: Eighteen women with sperm-immobilizing antibodies and 122 infertile
      patients with nonimmune etiology as controls. Infertile couples due to a male
      factor and with unknown etiology were excluded. INTERVENTIONS: All patients
      received the same IVF-ET program with GnRH agonist. MAIN OUTCOME MEASURES: Rates
      of fertilization and cleavage, implantation rate per embryo transferred and
      pregnancy rate (PR) in both test and comparison groups. RESULTS: The rate of
      fertilization in the antisperm group (61.3%) was significantly lower than that in
      the comparison group (76.8%). But the implantation rate per embryo transferred
      (23.5%) and consequently the modified PR per oocyte recovery procedure (34.4%) in
      immunologically infertile women were significantly higher than those in the
      comparison group (7.9% and 17.8%, respectively). CONCLUSIONS: Although sperm
      immobilizing antibodies prevent sperm-egg interaction, they do not seem to have
      any adverse effects on achievement of pregnancy. Moreover, the existence of
      antisperm immunity in woman with antisperm antibodies is suggested to be
      favorable for successful pregnancy by the IVF-ET procedure.

PMID- 7805930
TI  - Prospective randomized study on the cryopreservation of human embryos with
      dimethylsulfoxide or 1,2-propanediol protocols.
AB  - OBJECTIVE: To investigate the optimal protocol for cryopreservation of human
      embryos obtained from IVF. DESIGN: Prospective randomized study. SETTING:
      Consenting patients in an academic research environment. PATIENTS: Couples
      undergoing IVF. INTERVENTIONS: A cohort of 2,220 supernumerary multicellular
      embryos were obtained from 488 patients who were randomized over slow freezing
      protocols with dimethylsulfoxide (DMSO, 819 embryos), 1,2-propanediol (699
      embryos) or a mixture of DMSO and 1,2-propanediol (702 embryos). A total of 725
      embryos have been thawed (DMSO, 232 embryos; 1,2-propanediol, 250 embryos and
      DMSO and 1,2-propanediol, 243 embryos) for transfer in natural ovarian cycles.
      MAIN OUTCOME MEASURES: Embryo survival rate, embryo implantation rate, clinical
      pregnancy rate (PR), delivery rate, live-birth rate. RESULTS: The embryo survival
      rate was significantly higher with the DMSO protocol (52.6%) than with the 1,2
      propanediol (32.0%) or the DMSO and 1,2-propanediol protocols (34.9%). The
      clinical PR per thawing cycle was significantly higher in the DMSO protocol
      (17.2%) than in the 1,2-propanediol protocol (3.9%). The clinical implantation
      rate per embryo thawed was significantly different between a DMSO-frozen embryo
      (4.7%) and a 1,2-propanediol-frozen embryo (1.2%). A DMSO and 1,2-propanediol
      frozen embryo had a 3.7% chance of of implantation. The delivery rate per thawing
      cycle was significantly higher in the DMSO protocol (12.5%) than in the 1,2
      propanediol protocol (2.6%). The live-birth rates per embryo thawed were 3.5%,
      0.8%, and 2.9% in the DMSO, 1,2-propanediol, and DMSO and 1,2-propanediol groups,
      respectively. CONCLUSION: Supernumerary multicellular embryos as presented in
      daily clinical IVF practice have the highest chance of survival and of
      implantation after cryopreservation when DMSO has been used.

PMID- 7805931
TI  - Mathematical modelling of chemotherapy in HIV infection.
AB  - A mathematical model of CD4+ lymphocyte depletion in HIV infection is used to
      simulate and analyse the effect of AZT treatment. In most cases, permanent
      administration of AZT is observed to stop the CD4+ lymphocyte count decline and
      to stimulate their increase up to a new steady-state level, which depends on the
      intensity of AZT treatment, i.e. AZT dose. Temporary administration of AZT leads
      only to a temporary increase in CD4+ lymphocyte count. After the treatment is
      terminated, the count starts to decline again. However, the resulting
      prolongation of patient's survival exceeds the time interval of AZT
      administration. Interestingly, the survival prolongation is greater, if the
      treatment is started at five than at two years after the infection and there is
      no striking increase in survival time if a dose of AZT inhibiting 75% of HIV
      proliferation is used instead of a lower one inducing 25% inhibition only.

PMID- 7805932
TI  - Electron-microscopic demonstration of virus particles in acute lymphoblastic
      leukaemia in Sprague-Dawley rats.
AB  - Retrovirus-like particles were detected by the negative staining method in
      supernatants of lymph node and spleen cell suspensions prepared from Sprague
      Dawley rats with spontaneous acute lymphoblastic leukaemia (ALL). Similar
      particles were found in supernatants of cell suspensions from a lymphoma that
      developed after inoculation of lymph node and spleen cell suspension prepared
      from animals with spontaneous ALL into the subcutis of Sprague-Dawley recipients.
      On ultrathin sections, budding forms of the virus particles were seen as a dot at
      the periphery of neoplastically transformed cells.

PMID- 7805933
TI  - Adaptive response to ionizing radiation in normal and aneuploid human
      lymphocytes.
AB  - The ability to induce an adaptive response by low doses of gamma rays was studied
      in normal and trisomic lymphocytes (47, XX or XY, +21). The results indicate the
      presence of an adaptive response in lymphocytes of 3 normal donors, but in
      lymphocytes of 5 donors with trisomy 21 no significant adaptive response after
      irradiation with a low dose of gamma rays was found. There was similar
      chromosomal radiosensitivity in normal and trisomic lymphocytes (47, XX or XY,
      +21) irradiated with 1.50 Gy at the 48th hour after stimulation.

PMID- 7805934
TI  - Rapid distinguishing of three African green monkey cell lines: different
      morphology of chromosomes with nucleolus organizer regions (NORs).
AB  - Cell lines established from African green monkey kidney cells have been used over
      years in virology. It is possible to distinguish them by detailed karyology of
      banded metaphases or by iso-enzyme studies. Different morphology of NOR-bearing
      chromosomes in three African green monkey cell lines studied in our laboratory
      enables us to distinguish them in simple conventionally Giemsa-stained slides.
      Vero cells have two chromosomes with secondary constrictions with active NORs.
      One chromosome is a small submetacentric with secondary constriction on the long
      arm in the vicinity of centromere. The second one is rather metacentric with a
      smaller secondary constriction. In BGM cells we found two submetacentric
      chromosomes, one has a large secondary constriction, the other has a smaller
      secondary constriction. BS-C-1 cells have a large metacentric chromosome with
      secondary constrictions on both arms. In one investigation an additional large
      acrocentric chromosome with the secondary constriction on the long arm was found.
      Comparison with morphology of NOR-bearing chromosomes in a Rhesus monkey cell
      line is discussed. The method described here is particularly useful for a rapid
      discrimination of cell lines, produced in our Institute, for virological and
      diagnostic application in virological laboratories of the hygiene service and in
      hospitals.

PMID- 7805935
TI  - Hairlessness does not influence growth retardation in nude mice. Computer image
      analysis study.
AB  - Ossification in 4-week-old nu/nu and nu/+ BALB/c and BFU mice was studied by X
      ray analysis and by measurement of the thickness of the proximal tibial growth
      cartilage using CUE 4 Olympus computer image analysis. Not only altered
      architecture but also a significantly thinner proximal tibial growth plate was
      observed in athymic nu/nu as opposed to nu/+ and BFU mice. On the other hand, no
      significant differences were found between nu/+ and BFU littermates. Higher X-ray
      density of tail vertebrae was observed in nu/+ and BFU than in nu/nu mice. This
      comparison between athymic nu/nu and hairless euthymic BFU mice indicates that
      altered postnatal ossification in nude mice is not caused by hairlessness, but is
      due to other (immunological or endocrinological) differences.

PMID- 7805936
TI  - General principles of pharmacology.
AB  - Historically, the clinician was responsible for information about the sources,
      physical and chemical properties, compounding, and dispensing of drugs. These
      activities are now delegated to pharmacologists and pharmacists. Today the
      practitioner's responsibility requires the rational clinical use of therapeutic
      agents for the prevention, diagnosis, and treatment of disease. Understanding how
      chemicals act on body homeostasis at the molecular level is the foundation for
      developing new drugs. Understanding drug actions at the molecular level is also
      the basis for rational pharmacotherapy. In addition, it has been emphasized
      repeatedly that drugs seldom exert their beneficial effects without also causing
      adverse side effects. The inevitability of this therapeutic dilemma lends
      credence to the statement that there are no safe biologically active agents. In
      dealing with this certainty, once again, the clinician trained in molecular
      mechanisms of drug action, principles of disposition, pharmacotherapeutics, and
      toxicology has the advantage.

PMID- 7805937
TI  - Anxiolytic therapy. Oral and intravenous sedation.
AB  - Anxiety associated with dental treatment is a well recognized problem that has a
      negative impact on patients' willingness to seek care. Today, this anxiety can be
      controlled by the practitioner. This article describes those techniques for both
      oral and parenteral administration as well as the pharmacokinetics of the drugs
      most commonly used for anxiety control.

PMID- 7805938
TI  - Local anesthetics.
AB  - Local anesthetics have been especially important in establishing pain control as
      a fundamental accomplishment in clinical dentistry. When used conscientiously,
      local anesthetics are effective and safe. It is helpful for clinical dentists to
      understand the workings of these adjuncts. The more we understand them, the
      better we will be able to use them.

PMID- 7805939
TI  - Acetylsalicylic acid and acetaminophen.
AB  - Aspirin is the most extensively prescribed analgesic, antipyretic, and anti
      inflammatory agent. It is effective against the mild-to-moderate pain of
      inflammation. The best single dose of aspirin is that which is adequate to
      relieve pain; the proper dosage interval is that which sustains relief without
      causing toxicity. It would be unfortunate to withhold aspirin from a patient who
      desperately requires the relief provided by this most useful analgesic because
      there have been some adverse effects when it is used improperly. Acetaminophen is
      a suitable substitute for aspirin for its analgesic or antipyretic uses in
      patients in whom aspirin is contraindicated (e.g., prepartum patients, children
      with febrile conditions, patients with asthma, peptic ulcer, gouty arthritis,
      hyperuricemia, hemophilia or other bleeding disorders, and those taking
      anticoagulants). However, the general substitution of acetaminophen for aspirin
      as an analgesic is not recommended.

PMID- 7805941
TI  - The chemotherapeutic management of chronic and persistent orofacial pain.
AB  - The use of medication in chronic orofacial pain is not without risk. It is
      important to be vigilant regarding side effects, including abuse. The treatment
      of chronic pain can be frustrating and confusing because most patients with pain
      experience remissions and relapses. The initial report of reduced pain by the
      patient to any of the treatments that have been attempted may lead to false
      optimism about the nature of the condition or the potential long-term response to
      medication. With time the patient may report a reduced response to the medication
      and suggest either a higher dose or a different medication. In such patients it
      is important to reexamine the original differential diagnosis. When in doubt,
      additional consultation with pain centers, other clinicians with experience in
      managing patients with chronic pain, and consultation with the patient's
      physician may be needed. If the patient develops an abnormal personality or
      behavioral profile, referral to a specialist in behavioral medicine may also be
      needed. The treatment of chronic benign pain should proceed as planned, being
      careful not to place the patient in an "at-risk position" regarding medications
      and their effects or side effects.

PMID- 7805940
TI  - Nonsteroidal anti-inflammatory drugs for acute pain control.
AB  - This article reviews the use of nonsteroidal anti-inflammatory drugs, both alone
      and in combination with opioids, for pain of dental origin. Therapeutic
      recommendations, which balance therapeutic efficacy and the side effects
      associated with the use of analgesics in ambulatory patients, are described for
      preventing and managing acute postoperative pain.

PMID- 7805942
TI  - The management of odontogenic infections. A rationale for appropriate
      chemotherapy.
AB  - Odontogenic infections are one of the most frequently occurring infectious
      processes known to health practice. Significant changes have occurred in the use
      of antibiotics and antimicrobials since the use of chemotherapeutic agents became
      widespread. This article provides some important considerations for selecting
      appropriate chemotherapeutic agents during the management of odontogenic
      infections.

PMID- 7805943
TI  - Antibacterial prophylaxis.
AB  - Bacteremias of dental origin have been implicated as sources of infection in
      specific cardiac conditions, diabetes, neutropenia, kidney disease, splenectomy,
      and patients with prosthetic joints. This article reviews the relative risks of
      dental bacteremias in these patients, discusses the merits of various regimens,
      and presents current prophylactic antibiotic recommendations.

PMID- 7805944
TI  - Antimicrobials in periodontal practice.
AB  - Antimicrobial agents provide an additional means of combating the infective
      agents encountered in the periodontal diseases. Delivery methods include oral
      rinses, dentifrices, irrigation, local delivery, and systemic administration.
      Agents and delivery methods should be selected with the following criteria in
      mind: 1. The agent must be effective against the organisms present. 2. The agent
      must reach the desired site of action in appropriate concentration. 3. The agent
      must remain at the site for a sufficient period of time. When combined with a
      careful patient assessment and a considered diagnosis, the use of antimicrobial
      agents may prove to be an important adjunct in total periodontal therapy.

PMID- 7805945
TI  - Pharmacologic considerations in pediatric dentistry.
AB  - The unique physical, emotional, and developmental characteristics of the growing
      child make dental care particularly challenging for the practitioner. Children
      are not simply small adults, and the principles of adult pharmacotherapeutics are
      not easily extrapolated to "fit" the profile and needs of the child.
      Unfortunately, there is a paucity of literature concerning the use of
      pharmacologic agents in pediatric dentistry. This has been attributed largely to
      the fears and difficulties associated with working with children. In the
      literature available, comparison of studies and compilation of information are
      frequently impossible because of differences in selection criteria, study
      populations, and drug regimens used. Despite these difficulties, when young
      patients appear with pain, anxiety and infection, they must depend on the skills
      and knowledge of the practitioner to resolve their problem. Children have
      difficulties in locating or expressing pain, and fear may prevent any
      communication at all. The diagnosis and prevention of pain, anxiety, and
      infection are within the jurisdiction of the dentist and the parents. A working
      knowledge of the current trends in pharmacologic management of pain, infection,
      and anxiety enables the dentist to better treat and educate the parents in
      effective prevention, treatments, and therapy. The use of pharmacotherapeutic
      agents in unskilled hands can be potentially disastrous in children.
      Practitioners should use only those drugs in which they have been well trained to
      avoid excessive risk to the patient. The manufacturer's recommended dose should
      be followed carefully; if in doubt, consultation with the child's pediatrician is
      appropriate.

PMID- 7805946
TI  - Pharmacologic considerations in geriatric dentistry.
AB  - Drug administration to geriatric patients in the dental office requires special
      care. The margin of safety, or therapeutic window, in which the drug is safely
      effective may be greatly decreased because of physiologic changes with age, and
      pharmacokinetic and pharmacodynamic alterations. Realizing that the elderly are,
      as a group, more susceptible to adverse drug reactions, the addition of new
      medications must be undertaken with caution. Consulting with the patient's
      physician and a close working relationship with clinical pharmacists specializing
      in geriatrics can facilitate safe and effective drug prescribing.

PMID- 7805947
TI  - Adverse drug effects.
AB  - It has been emphasized repeatedly that drugs seldom exert their beneficial
      effects without also causing adverse side effects. The frequency of clinically
      important adverse effects is difficult to estimate, but the potential for drug
      drug and drug-disease interactions and drug-induced illness is high and lends
      credence to the statement that there are no safe biologically active agents.

PMID- 7805948
TI  - Glucose refractoriness of pancreatic beta-cells in rat models of non-insulin
      dependent diabetes.
AB  - A decreased insulin response, preferentially to glucose, has been considered a
      hallmark of non-insulin dependent diabetes mellitus (Type 2) in humans. Syndromes
      resembling human diabetes occur spontaneously in many animal species and can also
      be induced by treating animals with drugs or viruses, excising their pancreases
      or manipulating their diet. Among these models, rat diabetes induced by neonatal
      streptozotocin administration (n-STZ models) has been first recognized as an
      adequate tool to study the long-term consequences of a gradually reduced beta
      cell mass. More recently, the GK (Goto Kakisaki) Wistar rat has become available
      and is now considered as a promising spontaneous rat model of non-insulin
      dependent diabetes. We and others have found that defects in insulin secretion
      and action develop in the n-STZ and the GK models, which in many ways resemble
      those described in human non-insulin dependent diabetes. This review is aimed to
      sum up with a comparative approach, the informations so far collected in the n
      STZ and GK models concerning the cellular mechanisms leading to the
      desensitization of their beta-cells to glucose. Taken together, the data
      reinforce the view that the impairment of glucose-induced insulin release in n
      STZ and GK rats is clearly related to a defect in oxidative glycolysis. This
      leads to a severe decrease in the mitochondrial oxidative catabolism of glucose
      derived pyruvate. Its coincides with a lower ATP/ADP ratio in glucose-stimulated
      islets and a subsequent alteration of ionic events tightly coupled to the fuel
      function of the hexose in islet cells, i.e. the decrease in K+
      conductance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7805949
TI  - The role of Ca2+ in the release of pancreatic islet hormones.
AB  - The role of Ca2+ in initiating exocytosis of granule-bound secretory products was
      evaluated with respect to pancreatic islet hormones. Apart from stimulating the
      transfer of the granules to the plasma membrane and their subsequent extrusion, a
      rise of the cytoplasmic Ca2+ concentration ([Ca2+]i) may under certain conditions
      also have depressive effects on insulin release. Glucose has a bidirectional
      action on [Ca2+]i by stimulating both the entry of the ion and its removal by
      organelle sequestration and outward transport. The recognition of glucose as a
      secretory stimulus is based on sudden transitions between oscillatory and steady
      state [Ca2+]i at threshold concentrations of the sugar characteristic for the
      individual beta-cell. The intrinsic ability of each beta-cell to generate
      oscillations of [Ca2+]i and the subsequent synchronization of these signals
      result in a pulsatile release of insulin from isolated islets. Glucose regulation
      of this process is manifested as alterations of the amplitudes of the insulin
      pulses without effects on the frequency. It is suggested that electrical
      signalling from the beta-cells in combination with direct effects of glucose are
      important for regulating the release of glucagon and somatostatin.

PMID- 7805950
TI  - Multisite control of insulin release by glucose.
AB  - Glucose controls insulin release by beta-cells at two sites at least. By
      controlling the membrane potential, it controls the influx of Ca2+ and the rise
      in cytoplasmic Ca2+ which triggers exocytosis. At this level, the principal
      targets of glucose are the K(+)-ATP channels whose activity may be modulated by
      changes in the ATP/ADP ratio. A second, newly identified, mechanism of regulation
      is independent of changes in beta-cell membrane potential and of changes in
      Cai2+. It is not sufficient to induce insulin release, but serves to increase the
      response. This appears to be achieved through an amplification of the
      effectiveness of Cai2+ on the secretory process and may also depend on the
      changes in energy state of beta-cells.

PMID- 7805951
TI  - Role of eicosanoids in biosynthesis and secretion of insulin.
AB  - PURPOSE: The role of icosanoids, which are products formed from the metabolism of
      arachidonic acid, in pancreatic islet-cell function was investigated. PROCEDURES:
      Secretion and biosynthesis of insulin and glucagon, biosynthesis of icosanoids,
      and biosynthesis of enzymes and proteins necessary for icosanoid synthesis were
      studied in vitro, using perfused rat pancreas, isolated and incubated islets, and
      insulin-secreting islet-cell lines. FINDINGS: Certain exogenous prostaglandins
      stimulated the secretion of insulin and glucagon; leukotrienes stimulated insulin
      but not glucagon release. Leukotrienes inhibited glucose-induced insulin release,
      but promoted insulin biosynthesis. Islet cells produced prostaglandins. Although
      the production of leukotrienes in islet cells could not be demonstrated
      conclusively, glucose-responsive biosynthesis of 5-lipoxygenase and 5
      lipoxygenase-activating protein was considered evidence for leukotriene
      synthesis. Inhibitors of prostaglandin or leukotriene biosynthesis attenuated
      hormone secretion. CONCLUSION: Icosanoids produced in islet cells are involved in
      signal-transduction, in the form of a fine-tuning amplification of biosynthesis
      or secretion of insulin and glucagon in response to nutrient stimuli.

PMID- 7805952
TI  - Phosphoinositide metabolism and insulin secretion.
AB  - Secretion of insulin from beta cells of the pancreatic islets is regulated by
      glucose, its anaerobic metabolism and its metabolites. The phospholipids of the
      cell membrane the phosphoinositides are broken down by the activation of the
      enzyme phospholipase C either through the occupation of the receptor by an
      agonist or through the metabolism of glucose in the anaerobic glycolytic pathway.
      The hydrolysis of the phosphotidyl inositide-bisphosphate yields to the
      generation of Inositol 1, 4, 5-trisphosphate and diacylglycerol. Ins-1, 4, 5-P3
      increases the intracellular Ca2+ by releasing the sequestered Ca2+ in the
      endoplasmic reticulum and diacylglycerol activates the enzyme protein kinase C.

PMID- 7805953
TI  - New perspectives on the actions of sulphonylureas and hyperglycaemic
      sulphonamides on the pancreatic beta-cell.
AB  - Sulphonylureas and the hyperglycaemic sulphonamide diazoxide are commonly
      employed in the therapy of non-insulin-dependent (Type 2) diabetes mellitus and
      insulinoma, respectively. Stimulatory effects of sulphonylureas on insulin
      secretion and the inhibitory action of diazoxide are thought to be primarily
      mediated through modulation of the activity of ATP-sensitive K+ channels (K(+)
      ATP channels) in the beta-cell plasma membrane. Certain sulphonylureas are known
      to be internalised by the pancreatic B-cell. Recent studies suggest that these
      drugs and diazoxide can influence insulin secretion from electropermeabilized
      beta-cells in which K(+)-ATP channels and other plasma membrane ion channels are
      inoperative. This observation suggests that sulphonylureas and diazoxide interact
      with intracellular sites in the pancreatic B-cell which are directly involved in
      the regulation of the final stages of exocytosis.

PMID- 7805954
TI  - Islet Metabolism and Physiopathology. Proceedings and abstracts of a symposium.
      Istambul, Turkey, September 10-12, 1993.

PMID- 7805955
TI  - Insulin release in type 2 diabetes mellitus.
AB  - Impaired insulin response is a characteristic feature of Type 2 diabetes. Overt
      diabetes develops when beta-cells fail to release enough insulin to compensate
      for decreased insulin sensitivity. However, a subgroup of normal weight patients
      demonstrates a pronounced beta-cell secretory defect and a normal insulin
      sensitivity. The molecular basis behind the impaired insulin response in Type 2
      diabetes is not clear. Our studies in two animal models of this disease (GK rat
      and ob/ob mouse) suggest that an impaired glucose metabolism may be a primary
      defect in the stimulus-secretion coupling in the beta-cells in Type 2 diabetes.
      In the GK rat, three major alterations in the islet metabolism of glucose have
      been demonstrated: 1) increased glucose utilization but unchanged glucose
      oxidation; 2) increased glucose cycling and 3) decreased activity of the glycerol
      phosphate shuttle. In ob/ob animals we have found an increased rate of glucose
      cycling. These derangements might result in an incomplete closure of ATP
      sensitive K(+)-channels with a decreased insulin response as a consequence.

PMID- 7805956
TI  - Islet pathology in streptozotocin-induced auto-immune diabetic mice: new insights
      into clinical practice.
AB  - The pathogenesis of spontaneous remission in Type 1 diabetes is poorly
      understood. To clarify this particular phase of the disease, experimental
      autoimmune diabetes induced by multiple low doses of streptozotocin (M-STZ) in
      mice was used as an experimental tool. Balb/C mice received five doses of 40 mg
      of STZ (diabetic group) or citrate buffer (controls) during five consecutive
      days. Heparinized blood samples were collected from these animals' orbital sinus
      in the morning following 8-12 h of fasting, before and at the 7th, 14th and 21st
      day after the first injection of STZ. Plasma glucose, insulin and islet cell
      antibodies (ICA) were determined. The animals were killed at the 21st day; their
      pancreata and abdominal lymph nodes were removed for morphometric and
      immunocytochemical examinations. Induction of hyperglycaemia occurred on the
      first or second day after STZ injection. Sustained hyperglycaemia, hypo
      insulinaemia and islet cell antibody positivity were observed in diabetic
      animals. Morphometric analysis of the pancreata reveals a spectrum of mild to
      extensive mononuclear cell infiltration and varying degrees of beta cell
      destruction. In the same diabetic pancreas, morphometric analysis of islets'
      sections reveals a normal appearance in 42% and varying degrees of insulitis in
      58%; ductulitis in 20% and islets' necrosis in 48%, indicating that many immune
      assaults take place simultaneously and subsequently. Furthermore, plasmocytic
      transformation in diabetic lymph nodes was observed, disclosing the appearance of
      ICA's positivity. Concerning immunocytochemical findings, alpha, beta and delta
      cells were normal in appearance in controls; while beta cells of inflamed islets
      were filled with insulin and alpha cells appeared to be hyperplastic in the
      diabetic group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7805957
TI  - Physiology and pathology of islet metabolism.
AB  - This review reevaluates the possible roles of glut-2 underexpression, glucokinase
      gene mutation, glucose-6-phosphate hyperactivity, glycerophosphate dehydrogenase
      (FAD-linked) deficiency and glycogen accumulation in the pancreatic B-cell as
      contributive factors in the pathogenesis of Type 2 diabetes.

PMID- 7805958
TI  - Functional properties of isolated human pancreatic islets beneficial effects of
      culture and exposure to high glucose concentrations.
AB  - In order to assess the functional properties of human pancreatic islets we have
      evaluated insulin secretion, glucose metabolism and insulin mRNA synthesis.
      Particular attention was given to evaluate how culture and exposure to high
      glucose concentrations "in-vitro" influence the subsequent function of these
      cells. Islets were cultured for 1 and 7 days at 5.5 or 16.7 mM glucose
      concentrations. Insulin response to glucose, glucose+forskolin and
      leucine+glutamine was evaluated in freshly isolated and cultured islets.
      Catabolism of D-glucose was studied measuring D-(6-14C) glucose oxidation and D
      (5-3H) glucose utilization. Northern blot analysis was performed to measure
      insulin mRNA levels. In freshly isolated islets there a low insulin response to
      all stimulus, but especially to nutrient secretagogues. Total glucose utilization
      was also lower than expected, with preferential disturbances in mitochondrial
      oxidative events. Independently of glucose concentration, culture improved
      insulin release, glucose catabolism and especially glucose oxidation, and insulin
      mRNA synthesis. After 7-days culture, high glucose concentration in the medium
      exerted beneficial effects on the overall functional activities of human
      pancreatic islets. Our study, 1) indicates that functional properties, initially
      impaired in freshly isolated human islets, improve after culture and become
      comparable to those previously proposed for rodent islets; and 2) argues against
      high glucose concentrations producing a deleterious effect on human beta-cell
      function. Rather they point to the concept that high glucose levels are
      beneficial for human islets function after long-term exposure in-vitro.

PMID- 7805959
TI  - The use of an episiotomy in relation to the professional education of the
      delivery attendant.
AB  - In a group of 1272 primiparous women, who delivered spontaneously at the
      University Hospital of Leiden between 1 January 1988 and 31 December 1991, the
      relationship between the use of an episiotomy and the professional training of
      the delivery attendant has been studied, using multiple logistic regression (a
      random effects model to allow for patient-within-physician effects). The
      following factors were taken into account: birthweight, duration of the second
      stage of labour, supposed fetal distress, age and race of the mother, gestational
      age, duration of pregnancy and the year of the delivery. Based on the logistic
      regression model it is estimated that registrars and gynaecologists are 2.5 and
      3.4 times, respectively, more likely than midwives to perform an episiotomy.

PMID- 7805960
TI  - Uterine rupture in pregnancy reviewed.
AB  - Uterine rupture is associated with maternal and fetal mortality and morbidity. In
      developed countries there have been many recent advances in the management of
      labour. This study, therefore, reviewed this Hospital's experience of uterine
      rupture in the decade 1982 to 1991. Excluding cases of asymptomatic scar
      dehiscence, there were 15 cases of uterine rupture in 65,488 deliveries, giving
      an overall incidence of 1 in 4,366. There was no case of rupture in 21,998
      primigravidas. Of the 15 cases, only two occurred in 39,529 multigravidas without
      a previous uterine scar (1 in 19,765), and 13 cases occurred in the 3,961
      multigravidas with a previous caesarean section scar (1 in 304). Twelve of the 13
      ruptures after caesarean section occurred in the delivery immediately after the
      section. There were no maternal deaths but five (33%) patients required a
      hysterectomy. Three of the five perinatal deaths were attributable to the
      rupture. Ten of the 15 patients had labour induced, and a total of 13 patients
      received an oxytocic agent. Of the 15 cases, 8 were diagnosed during labour and 7
      postpartum. Compared with earlier reports from Dublin, the incidence of uterine
      rupture was low due to a decrease in the number of ruptures associated with
      trauma or obstetric manipulation. The main associated feature was previous
      caesarean section. This review highlights the risk of uterine rupture when an
      oxytocic agent is administered to a multigravid patient with a previous caesarean
      section scar.

PMID- 7805961
TI  - Fetal cerebral and renal Doppler in small for gestational age fetuses in
      hypertensive pregnancies.
AB  - The aim of the present work is to evaluate the hemodynamic disorders induced in
      several fetal vascular areas by maternal hypertension and to check the
      sensitivity and the specificity of the various Doppler parameters in the
      detection of small for gestational age (SGA) infants. The population consisted of
      90 pregnant mothers aged 26.3 +/- 5.8 years with pregnancy-induced hypertension.
      Seventeen of them delivered moderate small for age babies (between the 10th and
      5th centiles), without any neonatal complication. The opposition to flow in the
      fetal brain and kidney and in the placenta was evaluated using the Resistance
      Index (RI). The ratio of cerebral RI and umbilical RI, called the
      cerebroplacental ratio (CPR), was calculated and used as an indicator of fetal
      flow redistribution. The ability of CPR and renal RI to predict SGA at birth was
      evaluated; the sensitivity, specificity, positive predictive value, and negative
      predictive value for the CPR were 88.2%, 98.6%, 93.8% and 97.3%, respectively.
      The corresponding figures for the renal RI were 58.8%, 94.5%, 71.4% and 91%,
      respectively. Furthermore, in the SGA group, the abnormal renal RI values were
      both above and below the normal range, whereas the CPR values demonstrated
      consistent changes (always < 1). CONCLUSION: this investigation demonstrates that
      in pregnancy-induced hypertension (even with moderate growth retardation, and no
      neonatal complication), the diagnostic efficacy of CPR for predicting SGA at
      birth is very high and that of renal RI correlates very poorly with fetal growth.

PMID- 7805962
TI  - The attitudes of women and feasibility of screening for ovarian and endometrial
      cancers in inner city practices.
AB  - The study aimed to assess the attitudes of women and the feasibility of screening
      for ovarian and endometrial cancers using vaginal ultrasound should screening
      prove to be effective. A total of 4873 women aged 45-74 were registered with 9
      general practices in inner London. Of these, 1469 (30%) were ineligible for
      screening for ovarian and endometrial cancers as they proved to be the wrong age,
      had moved, or had undergone a total abdominal hysterectomy and bilateral salpingo
      oophorectomy. The proportion of ineligible women varied between practices (24
      39%) (P < 0.001). The adjusted response rate to a questionnaire on attitudes to
      ovarian and endometrial screening was 56% (1833/3360). Of the women, 1395 (76%)
      were willing to be screened with a significant difference between age groups,
      those over 65, at increased risk, being less willing (P < 0.001). Non-caucasians
      were more willing to be screened (P < 0.001) but educational attainment did not
      influence attitude to screening. Those women who were not very worried about
      vaginal instrumentation were more willing to be screened than those who were very
      worried (P < 0.001). The uptake rate for ovarian and endometrial screening, which
      is currently of unproven value, was 43% (1480/3360) with a significant difference
      between practices (33-49%) (P < 0.01).

PMID- 7805963
TI  - Number of follicles, oocytes and embryos in human in vitro fertilization is
      relative to serum estradiol and progesterone patterns during different types of
      ovarian hyperstimulation.
AB  - Preovulatory serum estradiol and progesterone levels as well as their ratio were
      compared in different types of ovulation induction in order to determine whether
      these findings could be used to predict the number of preovulatory follicles,
      number of oocytes aspirated and embryos obtained. Significantly more oocytes were
      retrieved by follicular aspiration and significantly more embryos developed in
      patients receiving gonadotropin-releasing hormone agonist and human menopausal
      gonadotropins than in those given other ovulation inductors. On days -2 and -1 of
      the cycle, serum estradiol levels were significantly lower in pure follicle
      stimulating hormone induction. Serum progesterone was significantly higher in
      pure follicle-stimulating hormone cycles on days -4 and -3. In clomiphene citrate
      and human menopausal gonadotropin induction, progesterone levels were
      significantly lower on days -2 and -1, and on the day of follicular aspiration.
      Ratios of estradiol/progesterone were lower in pure follicle-stimulating hormone
      group from day -3 to day -1 of the cycle. A significant correlation was found
      between estradiol and progesterone serum levels and the numbers of preovulatory
      follicles, oocytes and embryos. The study revealed the usefulness of serum
      estradiol and progesterone determinations in assisted reproduction.

PMID- 7805964
TI  - Reduced pregnancy outcome in patients with unilateral or bilateral hydrosalpinx
      after in vitro fertilization.
AB  - In a retrospective study, we compared 118 patients with hydrosalpinx and 157
      patients with bilateral salpingectomy entering an established in vitro
      fertilisation programme between 1988 and 1992. Patients with unilateral or
      bilateral hydrosalpinx had a lower clinical pregnancy rate, a higher miscarriage
      rate, and a lower ongoing pregnancy rate than patients with absent Fallopian
      tubes.

PMID- 7805965
TI  - Successful pregnancy after early luteectomy.
AB  - A 31-year-old women, para 1, was admitted with acute lower abdominal pain.
      Examination revealed a tender right adnexal mass confirmed by endovaginal
      ultrasonography. She reported a regular menstrual cycle of 30-31 days and was on
      day 31 of her cycle on admission. All laboratory results were normal and a
      urinary pregnancy test was negative. After 2 days a laparotomy was performed and
      an oophorectomy was carried out because of a bleeding ruptured right ovarian
      cyst. Histologic examination reported a haemorrhagic corpus luteum. Eight weeks
      after laparotomy a viable intra-uterine pregnancy was observed and finally a 3850
      g healthy male was delivered. An oophorectomy at a corrected gestational age of
      30 days did not disturb the course of the pregnancy.

PMID- 7805966
TI  - Single fetal demise in twin gestation resulting in the resolution of severe pre
      eclampsia.
AB  - A primigravida presenting with a twin pregnancy and severe pre-eclampsia which
      developed during early pregnancy is described. Complete resolution of symptoms
      and signs of pre-eclampsia were evident following the death of a growth-retarded
      single fetus. Pregnancy continued successfully until 35 weeks of gestation, when
      a single healthy infant was delivered. Few such cases of complete resolution of
      pre-eclampsia following the death of a single fetus are reported in the
      literature. The possibility that genetic susceptibility to pre-eclampsia is
      conferred by homozygosity for the same single recessive gene expressed by both
      mother and fetus is discussed.

PMID- 7805967
TI  - Combination of granulosa cell tumour and carcinoid in an imitation of appendix
      vermicularis within a mature teratoma--a unique case.
AB  - A case of primary carcinoid of the ovary in association with an imitation of
      appendix vermicularis is presented. These elements were thus parts of a mature
      teratoma. In the other ovary a granulosa cell tumour with a similar morphology
      was found. Following surgery no additional treatment was administered and the
      patient is well 13 years after the diagnosis.

PMID- 7805968
TI  - Preoperative diagnosis of a rudimentary uterine horn.
AB  - Two cases of rudimentary uterine horn were able to be diagnosed prior to
      operation. The case of rudimentary horn with cavity non-communicating to
      unicornuate uterus was easy to diagnose. Transabdominal ultrasonography and
      computed tomography (CT) demonstrated the uterus to have binodular structure and
      two uterine lumina. However, the case with pregnancy was difficult to diagnose.
      In this case, thick myometrium could be seen by ultrasonography to enclose the
      sac. In both cases hysterosalpingography revealed unicornuate uterus.

PMID- 7805969
TI  - Endometrial carcinoma arising within extensive intrauterine synechiae.
AB  - In patients with intrauterine adhesions severe enough to produce amenorrhoea,
      biologically active endometrium can undergo malignant change. To our knowledge,
      this is the first reported case of endometrial carcinoma arising within
      intrauterine synechiae. A 71-year-old woman receiving unopposed estrogen
      developed post-menopausal bleeding. At endovaginal sonography we detected a
      polypoid mass. Extensive intrauterine synechiae within the uterus were noted
      during hysteroscopy, and a polypoid lesion was seen adjacent to a synechia.
      Biopsy demonstrated endometrial adenocarcinoma arising from a synechia.
      Hysterectomy and bilateral salpingo-oophorectomy were performed. A well
      differentiated adenocarcinoma of the endometrium was demonstrated. Asherman
      syndrome and endometrial adenocarcinoma can exist simultaneously. In such cases,
      hysteroscopy is essential for diagnosis of synechiae and for target biopsy.

PMID- 7805970
TI  - The speculum.

PMID- 7805971
TI  - Ureteric stent in severe hydronephrosis of pregnancy.
AB  - Eleven women (12 pregnancies) were included in the study. A double-pigtail
      ureteric stent was passed under cytoscopic vision in 8 patients. The mean
      gestational age on insertion of the stents was 29 weeks (range, 25-35 weeks).
      Delivery took place at a mean of 39 weeks (range, 35-41 weeks). Stents remained
      in situ for a mean of 9 weeks (range, 6-14 weeks) before delivery and were
      removed 4-5 weeks postpartum. Double pigtail ureteric stents did not expose the
      women to infection. Renal function tests remained within the normal limits.
      Ureteric stent is an effective method for internal drainage of severe
      hydronephrosis during pregnancy.

PMID- 7805972
TI  - A prospective randomized clinical trial comparing a new oral sustained-release
      ritodrine with conventional tablets.
AB  - OBJECTIVES: Evaluation of maternal metabolic and cardiovascular responses to
      treatment with the new sustained-release oral ritodrine as compared with the
      conventional tablets. METHOD: Thirty-two pregnant patients who had successful
      intravenous tocolysis were randomly assigned to treatment with either ritodrine
      tablets or sustained-release capsules. After 5 days of the randomly determined
      first oral treatment each patient was shifted to the alternate ritodrine
      formulation for a further 5-day course. Each patient underwent metabolic and non
      invasive hemodynamic evaluation. RESULTS: Echocardiographic parameters during
      treatment with ritodrine tablets were not significantly different from during
      sustained-release capsules. Mean systolic blood pressure increased significantly
      during peak drug activity in patients treated with ritodrine tablets and not
      during treatment with the sustained-release form. Fasting plasma glucose levels
      were higher in patients on conventional tablets therapy than in patients on
      sustained-release ritodrine therapy (88.9 +/- 9 mg/dl vs. 78.7 +/- 8 mg/dl, P <
      0.05) while levels following a 50-g oral glucose challenge test did not differ
      significantly (135 +/- 32 mg/dl vs. 124.5 +/- 27 mg/dl) CONCLUSIONS: Because of
      fewer metabolic and cardiovascular side-effects, the new oral therapy offers some
      advantages over the presently available tablets.

PMID- 7805973
TI  - Pregnancy after myocardial infarction.
AB  - The occurrence of pregnancy in a patient after myocardial infarction remains a
      dilemma for both the cardiologist and the obstetrician. The majority of
      obstetricians and cardiologists are very reticent about pregnancy in a woman
      suffering from coronary disease. AIMS: The aims of this study are to evaluate the
      risks, the prognosis of pregnancy for women who had suffered from myocardial
      infarction and to propose guidelines for pre-pregnancy counselling and medical
      supervision of the pregnancy and delivery. METHODS: A review of literature has
      revealed 30 cases, 14 of which are sufficiently documented. Only one of these
      patients requested pre-pregnancy counselling. We add to this experience the case
      of a patient who, having had an infarction, was authorized to begin pregnancy.
      RESULTS: Most of the pregnancies in these patients evolve satisfactorily if the
      more frequent cardiovascular complications are diagnosed and treated rapidly.
      During the pregnancy, rest is the rule and any situation which risks to increase
      the myocardial work-load should be avoided. Normal vaginal delivery with epidural
      anesthesia is the preferred method. CONCLUSION: The maternal and fetal prognosis
      is good on condition of performing a pre-pregnancy examination and of setting up
      a multi-discipline surveillance of the pregnancy. The review of the literature
      does not confirm the surrounding pessimism concerning the patients becoming
      pregnant after myocardial infarction.

PMID- 7805974
TI  - Prevalence and influence of Mycoplasma hominis and Ureaplasma urealyticum in 218
      African pregnant women and their infants.
AB  - OBJECTIVES: To estimate the prevalence of Ureaplasma urealyticum (Uu) and
      Mycoplasma hominis (Mh) in the lower genital tract of pregnant women, their
      evolution during pregnancy, and the effect of these pathogens on the outcome of
      pregnancy in Equatorial Africa. STUDY DESIGN: 218 pregnant women were followed
      from before 20 weeks gestational age through delivery. Samples were taken from
      the cervix at every visit and from the newborn at delivery and tested for Uu and
      Mh. The data were analysed using Student's t-test, the Mann-Whitney, or the chi 2
      test. RESULTS: The prevalence of cervical colonization by Ureaplasma urealyticum
      and Mycoplasma hominis in pregnant women was 79% and 41% respectively.
      Colonization with Uu and Mh increased significantly throughout pregnancy (P <
      0.001). Their presence was associated with lower gestational age at delivery,
      lower birth weight and increased neonatal morbidity and mortality (P < 0.05).
      Erythromycin therapy did not have any effect on the evolution of Uu and Mh
      colonization during pregnancy. CONCLUSION: Uu and Mh are additional factors that
      might contribute to poor pregnancy outcome in a country where neonatal health is
      already impaired by many other microorganism.

PMID- 7805975
TI  - Reproductive health: a goal for all women.

PMID- 7805976
TI  - Can breech presentation at birth be predicted from ultrasound examinations during
      the second or third trimesters?
AB  - OBJECTIVES: To determine at which gestational age the ultrasound finding of a
      breech presentation should compel us to follow the pregnancy more closely with
      repeat ultrasound examinations. METHODS: A retrospective longitudinal
      investigation of ultrasound examinations in the second and third trimesters is
      reported. The study group consisted of 157 breech deliveries and a control group
      of 1325 vertex deliveries. RESULTS: In the study population (breech delivery)
      63.2% were presenting as breech during the 15th-19th weeks of pregnancy--almost
      the same percentage as in the vertex-born group (of which 55.2% were breech
      presentation). In the interval between 20 and 24 weeks the same relationship was
      observed (50.8% and 42.9%, respectively). From 25 weeks until delivery a
      statistically significant difference appeared between the breech-delivered group
      and the vertex-delivered group: during weeks 25-29 in the breech-delivered group,
      70.6% were breech presentation compared with 28.9% in the vertex-born group (P <
      0.0001). That difference increased as the pregnancy progressed. CONCLUSIONS:
      Patients found sonographically to be a breech presentation at 25 weeks' gestation
      or later are at high risk for malpresentation at delivery.

PMID- 7805978
TI  - Institutional maternal mortality in Mali.
AB  - OBJECTIVES: To measure the institutional maternal mortality ratio (MMR) in Mali
      and suggest ways to reduce it. METHODS: Routinely recorded data from 24 health
      institutions in three regions were reviewed for 1988 to 1992. RESULTS: The
      overall MMR in the institutions was 201 maternal deaths per 100,000 live births.
      Hemorrhage, toxemia and infections accounted for 80% of the 360 recorded maternal
      deaths, almost all of which were preventable. The main reasons why these
      conditions result in death lie in poor quality and maldistribution of health
      services, lack of transport and late use of allopathic services. CONCLUSIONS:
      Maternal mortality is still a major public health problem in Mali, even among the
      small proportion of women who reach health facilities. Substantial new
      initiatives are urgently needed to reduce this major cause of preventable adult
      female mortality.

PMID- 7805977
TI  - A simple alternative to parenteral oxytocics for the third stage of labor.
AB  - OBJECTIVE: To determine the effect of nipple stimulation on uterine activity
      during the third stage of labor. METHODS: Randomized controlled study comparing;
      (i) 15 min of nipple stimulation (n = 6), (ii) routine syntometrine injection (n
      = 3), (iii) no action/control (N = 5). Uterine activity was continuously measured
      using the placenta as an in-situ hydrostatic bag connected to a pressure
      transducer. RESULTS: Compared to controls uterine pressure was higher during
      nipple stimulation (103 mmHg vs. 70.8 mmHg, P = 0.04). The duration of the third
      stage and blood loss tended to be reduced with nipple stimulation compared to
      controls (20.3 vs. 12.3 min) and (257 vs. 166 ml) respectively but was not
      significant. Similar differences were observed between syntometrine and control
      groups. CONCLUSIONS: For women in developing countries where parenteral oxytocics
      are not available, nipple stimulation might reduce the incidence of postpartum
      hemorrhage. A larger trial now seems warranted.

PMID- 7805979
TI  - A comparison of manual vacuum aspiration (MVA) and sharp curettage in the
      management of incomplete abortion.
AB  - OBJECTIVES: A prospective longitudinal study was carried out in two Harare
      hospitals to determine whether manual vacuum aspiration (MVA) was as safe and as
      effective as sharp curettage for treatment of incomplete abortion. METHODS:
      Demographic and clinical data were collected over a 3-month period on 589 women
      treated with sharp curettage for incomplete abortion < or = 12 weeks gestation.
      One year later, after faculty and staff at the two hospitals were trained to use
      MVA, data were similarly collected on 834 women treated with MVA for incomplete
      abortion. RESULTS: Based on procedure-related complications at the time of
      treatment, MVA was found to be as safe as sharp curettage in treating incomplete
      abortion < or = 12 week gestation. MVA was more effective than sharp curettage in
      achieving complete uterine evacuation (0% incomplete evacuations vs. 0.7%, P <
      0.05). CONCLUSIONS: Given the safety and effectiveness of the MVA procedure and
      the potential for reducing health care costs and improving patient management,
      this technology should be considered by health care systems in developing
      countries for improving treatment of abortion complications.

PMID- 7805980
TI  - Screening for consumptive coagulopathy in preeclampsia.
AB  - OBJECTIVE: To identify a practical and cost-effective profile of tests to screen
      for consumptive coagulopathy in preeclampsia (PE). METHODS: Retrospective
      analysis of the results of measurements of platelet count, prothrombin time (PT),
      activated partial thromboplastin time (APTT), plasma fibrinogen and D-dimers in
      100 patients presenting with PE uncomplicated by other disease or antepartum
      hemorrhage. Twenty-four patients had pregnancy-induced hypertension only, and 76
      hypertension with proteinuria. RESULTS: The incidence of abnormal tests on
      presentation was raised D-dimers 34%, thrombocytopenia 14%, prolonged APTT 12%,
      prolonged PT 3%, and low fibrinogen 2%. Prolonged APTT without thrombocytopenia
      occurred in 8% of patients. In 19 patients with elevation of D-dimers alone, only
      one showed evidence of consumption of coagulation factors on subsequent testing.
      CONCLUSIONS: A combination of platelet count and APTT is probably a practical and
      cost-effective combination to screen for consumptive coagulopathy in PE.

PMID- 7805981
TI  - Cervical cancer in young women: a poorer prognosis?
AB  - OBJECTIVE: The existence of an aggressive form of cervical carcinoma affecting
      young women is studied by survival analysis of a large patient population.
      METHOD: Between 1969 and 1986, 1577 cases of cervical cancer were treated
      according to well-defined policies at the University Department of Obstetrics and
      Gynaecology in Debrecen, Hungary. Patients' records were reviewed to obtain data
      for survival analysis. Kaplan-Meier survival curves were generated for each stage
      and stratified for age. The log-rank test was used to compare the survival of
      younger and older patients at each stage. Multivariate analysis was performed to
      control for stage and treatment type when 5-year survival trends across four
      different age groups were examined. RESULTS: Comparison of survival of patients
      under 35 and over 35 years of age, and also those under 40 and over 40 years of
      age revealed no significant differences. Five-year survival across the < 30, 30
      39, 40-49 and > or = 50 years age groups showed no significant trend. No
      differences in survival were revealed when the comparison was controlled for
      stage of disease and treatment type. CONCLUSION: Results suggest that cervical
      carcinoma in young women is not more aggressive than in other age groups.

PMID- 7805982
TI  - Evaluation of transvaginal color Doppler sonography, transvaginal sonography and
      CA 125 for prediction of ovarian malignancy.
AB  - OBJECTIVES: To evaluate the efficacy of color Doppler ultrasonography as the
      predictor of malignant ovarian tumors and to compare the results with CA 125
      levels and ultrasonographic morphological patterns. METHODS: We compared color
      Doppler ultrasound with sonographic findings and serum CA 125 levels for
      predicting ovarian malignancy in 16 patients with malignant and 12 patients with
      benign ovarian tumors. RESULTS: There was a significant difference in pulsatility
      index (PI) value of ovarian vessel between benign and malignant tumors (2.42 +/-
      0.67 for benign and 1.35 +/- 0.78 for malignant, respectively, P < 0.01). The
      specificity of morphological findings and CA 125 was lower than that of PI
      measurements, but sensitivity was not different between the three methods. In
      addition, the combination of color Doppler and CA 125 or morphological
      assessments resulted in a sensitivity of 100% and a negative predictive value of
      100%, respectively. CONCLUSION: PI measurements by transvaginal color Doppler
      ultrasound combined with CA 125 levels or morphological findings could be an
      accurate and appropriate screening method for ovarian tumors.

PMID- 7805983
TI  - Effect of blood transfusion in patients with gynecologic malignancy.
AB  - OBJECTIVES: To determine the effect of blood transfusion on long-term outcome
      (disease-free interval, recurrence of disease after treatment, and survival) in
      women with invasive gynecologic malignancy. METHODS: In this retrospective study,
      125 patients with gynecologic malignancy were assessed over a 36-month period.
      The variable of whether patients received blood transfusion during therapy was
      used to divide the sample into two groups. RESULTS: There were no differences in
      the age, ethnicity, and site-stage of tumor of the two groups. Treatments
      (surgery, radiotherapy, chemotherapy, or multimodal) were similar between the two
      groups, as were initial hematocrits. The disease-free interval was significantly
      better in women who did not receive homologous blood (P < 0.001). Life table
      analysis illustrated that more patients were alive and free of disease if they
      did not receive blood (P < 0.001). Likewise, persistence-recurrence of cancer was
      more common in the transfusion group (P < 0.001). Finally, overall survival time
      was adversely affected by transfusion (P = 0.045). CONCLUSIONS: The use of blood
      products in patients with invasive gynecologic cancer is associated with enhanced
      recurrence or persistence of malignancy, a decrease in the disease-free interval,
      and reduction in the probability of survival without evidence of disease.

PMID- 7805984
TI  - Topical testosterone in the treatment of vulvar lichen sclerosus.
AB  - OBJECTIVES: Comparison between 2% testosterone propionate and petrolatum ointment
      in the treatment of vulvar lichen sclerosus in a randomized, double-blind,
      controlled clinical study. METHODS: Fifty-eight consecutive patients with
      histologically confirmed vulvar lichen sclerosus were enrolled. They underwent a
      1-year period of topical treatment with either medication, with clinical
      evaluations of symptoms and gross appearance at 2-month intervals, followed by
      histological evaluation at the end of the treatment period. Statistical analysis
      was performed according to the chi-squared test and the Student-Newman-Keuls
      test. RESULTS: A substantial improvement in symptoms was achieved in 20 (66.6%)
      patients in the testosterone group and in 21 (75%) patients in the placebo group.
      No statistical differences were observed between the two groups. Gross changes
      were observed in a few cases and no case demonstrated histologic modifications.
      CONCLUSIONS: Petrolatum ointment is as effective as 2% testosterone in the
      treatment of vulvar lichen sclerosus.

PMID- 7805985
TI  - Primary twin ovarian pregnancy.
AB  - A 20-year-old-woman, gravida II, para I, was admitted to the hospital with
      vaginal bleeding 17 weeks after her last menstrual period. Her pelvic examination
      was found to be compatible with 3.5 months of pregnancy by the attending
      physician. Ultrasonographic examination revealed an empty uterus and two dead
      fetuses with biometric data consistent with 14 weeks of pregnancy located in the
      left ovarian region. She was subjected to an explorative laparotomy and an intact
      gestational sac including the left ovary with normal tubes was observed; a
      unilateral salpingo-oophorectomy was carried out. Histologic studies confirmed a
      twin ovarian pregnancy. Although rare, ovarian pregnancy should be considered
      when approaching a case of ectopic pregnancy. Early diagnosis is generally based
      on ultrasonographic findings. Advanced cases with unruptured sac and multiple
      gestations may also be present.

PMID- 7805986
TI  - Attitudes toward current pregnancy among women attending an antenatal clinic in
      Ethiopia.

PMID- 7805987
TI  - Quality and quantity ratios of obstetric care in the gypsy and non-gypsy
      population in Hungary.

PMID- 7805988
TI  - Conservative management of pelvic spleen.

PMID- 7805989
TI  - Cell-mediated immunity in invasive cervical carcinoma associated with human
      papillomavirus types 16 and 18 infection.

PMID- 7805990
TI  - Endometrial polyps, cystic glandular hyperplasia and atypical leiomyoma
      associated with tamoxifen therapy.

PMID- 7805991
TI  - Aberrant adnexal blood supply.

PMID- 7805992
TI  - Uterine leiomyomata. Number 192--May 1994. ACOG technical bulletin.

PMID- 7805993
TI  - Introduction of gynecologic endoscopic surgery in an African setting.
AB  - The new operative endoscopic techniques have been fully tried in the
      industrialized world and have spread to all surgical specialities. These new
      technologies present an obvious advantage for certain gynecologic pathologies
      which are particularly common in Africa. For pelvic inflammatory diseases,
      ectopic pregnancies and tubal sterility, laparoscopic surgery enables an initial
      assessment of disease, a less traumatic treatment and therefore a better long
      term prognosis for fertility and reduced postoperative morbidity. Recently, an
      operative endoscopic unit performing laparoscopic surgery and endoscopic
      resections was created at the Centre Hospitalo-Universitaire de Yaounde in
      Cameroon. This facility is the result of close collaboration between the
      University of Yaounde and the University Hospital of Clermont-Ferrand. This
      operative endoscopic unit has been functioning since April 1992. The authors
      discuss the difficulties involved in such projects, such as initial investment,
      maintenance of equipment and in particular training of the surgical team.

PMID- 7805994
TI  - Changing trends in maternal mortality over a decade.
AB  - OBJECTIVES: To study the change in trend in maternal mortality over the last
      decade and to find out specific causes of death. METHOD: A retrospective study
      was carried out at Lady Harding Medical College, New Delhi, to analyze the causes
      of maternal deaths. The admission ledgers of patients admitted over two 3-year
      periods (1979-1981 and 1989-1991) were studied to ascertain the total number of
      maternal deaths and the specific causes of death. RESULTS: One hundred fifty
      eight deaths occurred during 1979-1981 and 149 deaths during 1989-1991. During
      the same period there were 23,098 and 37,763 total births, respectively, the
      overall maternal mortality rate thus significantly declining from 684/100,000
      total births in 1979-1981 to 394/100,000 total births in 1989-1991. Sepsis
      followed by hemorrhage and hepatitis were the leading causes of maternal deaths
      over the decade. CONCLUSION: Health education and availability of health
      services, largely at a community level, would contribute to reducing the
      incidence of preventable causes of maternal deaths such as sepsis and hemorrhage.

PMID- 7805995
TI  - Vaginal delivery after one cesarean section.
AB  - OBJECTIVE: To determine the success rate and safety of vaginal delivery after a
      previous cesarean section in a South African teaching hospital serving a
      developing community. METHOD: One hundred eighty-nine women with a history of one
      previous cesarean section were studied during a 10.5-month period. Maternal
      morbidity was studied in 92 of these patients who had infants weighing 2500 g or
      more. During the study period 5044 women delivered at the hospital. RESULTS: In
      the study group of 189 women, 85 (44.9%) delivered vaginally, 65 (34.4%) by
      cesarean section during labor and 39 (20.6%) had elective cesarean sections. One
      maternal and two perinatal deaths occurred. In the subgroup of 92 women with
      babies weighing 2500 g or more at birth, 10 women (10.9%) experienced morbidity
      related to trial of scar. CONCLUSION: Vaginal birth was accomplished less often
      in this population compared with reports from developed countries, but the
      procedure was equally safe.

PMID- 7805996
TI  - Effects of a maternity waiting home on adverse maternal outcomes and the validity
      of antenatal risk screening.
AB  - OBJECTIVES: To evaluate the effect of a maternity waiting home (MWH) on adverse
      maternal outcomes and the validity of antenatal risk criteria in predicting
      dystocia. METHOD: A hospital-based cohort study was conducted at a district
      hospital in Zimbabwe. Information on the presence of antenatal risk factors, stay
      at an MWH, and mode and outcome of delivery was collected for each woman
      delivering at the hospital during 1989-1991. RESULTS: The risk of obstructed
      labor was 16 times higher for those not attending an MWH (n = 2915) than for
      those who did attend an MWH (n = 1573) (1 vs. 0.06%, P < 0.005). Among the non
      users, 0.3% suffered a ruptured uterus compared with none of the MWH users. The
      presence of any one of the antenatal risk criteria used in Zimbabwe had a
      sensitivity of 78%, a specificity of 51% and positive predictive value of 25% for
      predicting dystocia. CONCLUSION: MWHs and antenatal risk screening are policy
      options for safe motherhood programs in settings where emergency obstetric
      services are not easily accessible.

PMID- 7805997
TI  - Estimating maternal mortality in rural areas of Mexico: the application of an
      indirect demographic method.
AB  - OBJECTIVE: To measure maternal mortality levels in rural areas of Mexico.
      METHODS: In a cross-sectional study, a census of 13,378 households was carried
      out in the municipalities of Yecapixtla and Tlaltizapan, Morelos, Mexico.
      Information on 10,443 subjects from 12 to 49 years old was included in the
      analysis. An indirect method of measuring maternal mortality--the sisterhood
      method--was used to estimate maternal mortality. Information about the number of
      sisters of the interviewees who died due to maternal causes was collected in the
      census. With this information, estimates of maternal mortality related to a
      period of 10-12 years before the application of the census were obtained. An
      innovation to the original method was the calculation of a confidence interval
      for the estimated maternal mortality rate (MMR). RESULTS: The MMR in this region
      was 18.68/10,000 live births (95% CI 15.79-21.58/10,000 live births). The average
      risk of dying due to maternal causes was 1 in 87 for women between 12 and 49
      years of age. CONCLUSIONS: The sisterhood method was effective for estimating
      maternal mortality in a small region, with no previous information about this
      indicator. The method proved to be useful for identifying a priority region for
      the implementation of maternal mortality reduction programs. Furthermore, the
      method was particularly convenient since it was applied as part of a multipurpose
      survey.

PMID- 7805998
TI  - External four-channel tocography during delivery.
AB  - OBJECTIVE: A four-channel tocographic technique was developed in order to improve
      present knowledge of spatial uterine motility. METHOD: Fifty-four women were
      monitored during labor. Four pressure transducers were attached in a square
      around the umbilicus. RESULTS: The origin of uterine contractions was generally
      determined to be in the upper right segment of the uterus. The rate of operative
      deliveries was decreased in the case of predominant upper right origin of labor.
      Most of the contractions with clear propagation patterns originated on the upper
      right side, continued to the left and then spread to the lower right part of the
      uterus. The highest relative intensity was also measured on the upper right side.
      CONCLUSION: Predominant upper right origin of labor may be important for
      unassisted or spontaneous delivery.

PMID- 7805999
TI  - Transvaginal ultrasound in threatened abortions with empty gestational sacs.
AB  - OBJECTIVE: To determine whether transvaginal ultrasound criteria alone can
      distinguish viable from non-viable gestational sacs at a single examination.
      METHOD: A prospective descriptive study was undertaken and analysis performed on
      211 pregnancies complicated by threatened abortion and empty gestation sacs
      diagnosed by transvaginal ultrasound. The main outcome measure was the final
      diagnosis of viable or non-viable gestation on subsequent transvaginal
      sonography. RESULTS: The study shows that a single transvaginal ultrasound
      examination is useful in differentiating viable from non-viable gestation sacs.
      The mean sac diameter (MSD) was found to be the most useful criterion for
      determining non-viability. An MSD of > or = 17 mm that lacked an embryo and an
      MSD of > or = 13 mm without visible yolk sac were reliable predictors of non
      viable gestation sacs at a single examination with 100% specificity and 100%
      positive predictive value. An MSD > or = 13 mm without visible yolk sac was the
      most sensitive criterion. Using MSD criteria, 73% of non-viable gestations could
      be reliably identified without any false-positive diagnoses. Deformed shape, low
      position and thin decidual reaction are strong indicators of non-viable
      gestations but are not 100% accurate. There is still a significant proportion of
      empty sacs, where no accurate distinction between viable and non-viable can be
      made according to one criterion at a single examination and in these cases serial
      examinations should be carried out before any active management is advocated.
      CONCLUSION: In most cases, transvaginal sonographic criteria alone can
      distinguish viable from non-viable empty gestational sacs at a single
      examination.

PMID- 7806001
TI  - Score prognosis for the infertile couple based on historical factors and sperm
      analysis.
AB  - OBJECTIVE: To identify variables, obtained from historical factors and sperm
      analysis, associated with greater chances of pregnancy in infertile couples.
      METHODS: The study was carried out in Cordoba, Argentina. The characteristics of
      247 couples consulting for infertility who achieved pregnancy within 3 years of
      their first visit were compared with those of 312 couples who did not become
      pregnant. We evaluated the relationship between the age of the woman and her
      partner, the type and duration of infertility, length of the last three menstrual
      cycles, history of pelvic surgery in the woman, and testicular volume, sperm
      density, motility and morphology in her partner, and the achievement of
      pregnancy. For the analysis, logistic regression was used. RESULTS: Six variables
      had a predictive value: sperm morphology, the woman's age, type and duration of
      infertility, her history of pelvic surgery, and duration of menstrual cycles.
      CONCLUSIONS: The best prognosis for future fertility in infertile couples is
      correlated with a higher percentage of normal sperm morphology, younger woman's
      age, secondary infertility, fewer years of infertility, negative history of
      pelvic surgery, and abnormal menstrual cycles.

PMID- 7806000
TI  - Type-IV collagenase and tissue inhibitor of metalloproteinase in ovarian cancer
      tissues.
AB  - OBJECTIVE: We examined the specific expression of gelatinase/type-IV collagenase
      and tissue inhibitor of metalloproteinase (TIMP) in clinical ovarian cancer
      tissue. METHODS: Molecular weight-specific gelatinase/type-IV collagenase
      activity was examined by sodium dodecyl sulfate (SDS)-polyacrylamide gel
      electrophoresis in which substrate was included (zymography). The expression of
      TIMP mRNA was examined by Northern blot analysis. RESULTS: Zymography revealed
      that in ovarian cancer the activity of a 92-kDa gelatinase/type-IV collagenase
      was always greater than that of a 64-kDa gelatinase/type-IV collagenase in
      contrast to the situation in the normal ovary. Northern blot analysis revealed no
      remarkable difference of TIMP mRNA expression between cancer and normal ovarian
      tissues. CONCLUSIONS: These results indicate that the higher activity of the 92
      kDa gelatinase/type-IV collagenase enzyme, relative to that of the 64-kDa enzyme,
      is involved in the malignant phenotype of ovarian cancer, while the inhibitor of
      these enzymes, TIMP, is distributed in a widespread fashion in the tissue, and
      its levels are not correlated with the malignancy.

PMID- 7806002
TI  - Idiopathic transient osteoporosis of the hip in pregnancy.
AB  - OBJECTIVE: To study the nature of a condition called transient osteoporosis of
      the hip (TOH) in pregnancy. METHOD: Fifty-three cases of this syndrome of unknown
      etiology have been reviewed and an additional case has been added. RESULT AND
      CONCLUSION: TOH is characterized by hip joint pain during the 3rd trimester of
      pregnancy and signs of demineralization of the femoral head. The course is benign
      with recovery shortly after birth. No specific therapy is required except bed
      rest.

PMID- 7806003
TI  - Uterine myxoid leiomyosarcoma and CYVADIC-etoposide therapy.
AB  - OBJECTIVES: To conduct a pathological characterization of rare uterine myxoid
      leiomyosarcoma (MLS) and establish an effective chemotherapy for metastasis after
      hysterectomy. METHODS: Histological and immunohistochemical methods were used to
      characterize the type of uterine MLS in a 39-year-old female. For multiple lung
      metastases found 3 months after operation, CYVADIC (400 mg cyclophosphamide, 1 mg
      vincristine, 50 mg epirubicin and 400 mg dacarbazine per body for one course) and
      oral etoposide (50 mg/body per day for 2 weeks) were applied. RESULTS: The
      rapidly enlarging uterine tumors exhibited gelatinous cut surfaces, a high count
      of 30 mitotic cells per 10 hpf and mucinous stroma, indicating a rare high
      mitotic type of uterine MLS. The two-course CYVADIC-etoposide therapy was
      effective for disseminated pulmonary metastases. CONCLUSION: The present MLS was
      a rare high-mitotic type. CYVADIC-etoposide was an optional effective
      chemotherapy for lung metastasis in this case.

PMID- 7806004
TI  - Quadruplet pregnancy--successful outcome using indomethacin.

PMID- 7806005
TI  - Advanced abdominal intraligamentary pregnancy with live birth.

PMID- 7806006
TI  - Hyperphosphatemia during magnesium sulfate infusion.

PMID- 7806007
TI  - Ectopic pregnancy and anesthesia in Gambia.

PMID- 7806008
TI  - Clinical presentation of cervical carcinoma in Kumasi, Ghana.

PMID- 7806009
TI  - Postmenopausal hydrometrocolpos.

PMID- 7806010
TI  - Genital human papillomavirus infections. Number 193--June 1994 (Replaces No. 105,
      June 1987). ACOG technical bulletin.
AB  - Knowledge of HPV infection is a rapidly changing area which presents a diagnostic
      and therapeutic dilemma. The clinical expression of HPV infection is highly
      variable and includes spontaneous regression and recurrence. A variety of
      molecular biologic methods are available for HPV detection and typing. The role
      of these diagnostic tools in clinical management is currently being defined.
      Several therapy options exist, and the choice of treatment depends on the
      physician and the circumstances and desires of the patient. The management of the
      patient with HPV includes recognition that the disease process cannot necessarily
      be cured, nor can the viral infection be totally or reliably eradicated from the
      genital tract with current methods.

PMID- 7806011
TI  - Adolescents' right to refuse long-term contraceptives. Number 139--June 1994.
      Committee on Adolescent Health Care.

PMID- 7806012
TI  - The role of the obstetrician-gynecologist in the diagnosis and treatment of
      breast disease. Number 140--June 1994 (Replaces No. 67, February 1989). Committee
      on Gynecologic Practice.

PMID- 7806014
TI  - In vitro study of the carry-over effect associated with early diabetic
      embryopathy in the rat.
AB  - Embryos were recovered from diabetic rats on day 5 of pregnancy and incubated in
      vitro for up to 72 h. Compared to control embryos, blastocysts from diabetic rats
      showed a marked impairment in growth that resulted at 48 h in a higher rate of
      degeneration and a lower morphological score in the developing population. After
      72 h in vitro, fewer developing blastocysts from diabetic rats formed
      trophoblastic outgrowths and fewer of those implanted developed an inner cell
      mass when compared with the control group. When assessed for their cell content,
      blastocysts from diabetic rats contained fewer cells than control embryos at the
      start of the culture. This difference persisted, and even worsened, during the
      ensuing incubation period. The increasing cellular deficiency in blastocysts from
      diabetic rats was primarily located to their inner cell mass lineage but
      trophoblast growth was also affected. When trophoblast outgrowths were compared
      for their surface area and number of nuclei, those collected from diabetic rats
      were smaller, contained fewer nuclei and had a higher proportion of giant nuclei
      than control outgrowths. Our data thus demonstrate that despite their removal
      from the abnormal intra-uterine environment, blastocysts from diabetic rats
      remain functionally affected by their early exposure and fare less well than
      control embryos cultured under the same standard conditions.

PMID- 7806015
TI  - The role of islet secretory function in the development of diabetes in the GK
      Wistar rat.
AB  - Insulin secretion and glucose metabolism were compared in islets isolated from GK
      Wistar rats (a non-obese, spontaneous model of non-insulin-dependent diabetes
      mellitus) and control Wistars aged 8 and 14 weeks. By 8 weeks of age, GK Wistar
      rats were clearly diabetic as indicated by non-fasting plasma glucose
      concentrations and impaired glucose tolerance. Islet insulin content was not
      significantly different to controls at either age. In islets from 14-week-old GK
      Wistar rats glucose-stimulated insulin release (6-16 mmol/l glucose) was
      significantly reduced to 25-50% of controls in static incubations (p < 0.001). In
      perifusion, glucose-stimulated insulin release was reduced by 90% for first phase
      (p < 0.01) and by 75% for second phase (p < 0.05). The responses to arginine and
      2 alpha Ketoisocaproate in islets were similar to those in controls. In contrast,
      islets isolated from 8-week-old GK Wistar rats exhibited no significant reduction
      in glucose-stimulated insulin secretion in static incubations. In perifusion,
      although both first and second phases of glucose-stimulated insulin release were
      slightly reduced, these were not significantly different to controls. Islets from
      8-week-old GK Wistar rats failed however to respond to stimulation by
      glyceraldehyde. Raising the medium glucose concentration to 16 mmol/l
      significantly increased rates of glucose utilisation ([3H] H2O production from 5
      [3H] glucose) and oxidation ([14C] CO2 production from U-[14C] glucose) in islets
      isolated from 8-week-old control and GK Wistar rats, respectively.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7806013
TI  - Vascular factors in diabetic neuropathy.
AB  - Despite considerable research we still do not have a comprehensive explanation
      for the pathogenesis of diabetic neuropathy. Although chronic hyperglycaemia is
      almost certainly involved, it is not known whether the primary pathology is
      metabolic, microvascular, or an interaction between the two. Hyperglycaemia
      induced polyol pathway hyperactivity associated with nerve sorbitol accumulation
      and myo-inositol depletion may play a part in the genesis of diabetic neuropathy.
      The case for microvascular disease in diabetic neuropathy is now strong. Fibre
      loss in human sural nerve is multifocal, suggesting ischaemia. The degree of
      vessel disease has been related to the severity of neuropathy. People with
      chronic obstructive pulmonary disease develop the so called "hypoxic neuropathy"
      in which similar microvascular changes occur as in diabetic neuropathy. In rats
      with experimental diabetic neuropathy nerve blood flow is reduced and oxygen
      supplementation or vasodilator treatment improved the deterioration in conduction
      velocity and nerve blood flow. Similarly, in human diabetic neuropathy, there is
      impaired nerve blood flow, epineurial arterio-venous shunting and a reduction in
      sural nerve oxygen tension. At what stage during the development of nerve damage
      these changes occur is yet to be determined.

PMID- 7806017
TI  - Impaired skeletal muscle glycogen synthase activation by insulin in the Goto
      Kakizaki (G/K) rat.
AB  - The Goto-Kakizaki (G/K) rat is an animal model of non-insulin-dependent diabetes
      mellitus, with early hyperglycaemia, hyperinsulinaemia, and insulin resistance.
      We have studied the effect of insulin on the activation of glycogen synthase in
      the G/K rat and in the original parent strain, the Wistar rat. After insulin
      injection, glycogen synthase I activity, glycogen synthase phosphatase activity
      and glucose 6-phosphate content in skeletal muscle were significantly increased
      in the Wistar rats. In the G/K rats, insulin injection resulted in a reduced
      activation of skeletal muscle glycogen synthase, which was not significant when
      compared with the control rats without insulin, and no increases in glycogen
      synthase phosphatase and glucose 6-phosphate were seen. In adipose tissue the
      activation of glycogen synthase by insulin was normal in the G/K rats. Previous
      investigations have shown that glucose disappearance rates are low in the G/K
      rat. However, stimulation of glucose transport was reported to be normal in the
      G/K rat. A defective activation of glucose accumulation into glycogen by skeletal
      muscle may contribute to explain the hyperglycaemia in the G/K rat.

PMID- 7806016
TI  - Mechanisms underlying the insulinostatic effect of peptide YY in mouse pancreatic
      islets.
AB  - Peptide YY is an insulinostatic peptide which is released into the circulation
      from the intestinal mucosa upon food intake. Peptide YY is also co-stored with
      glucagon in the secretory granules of the pancreatic alpha cells. We examined the
      mechanisms underlying the insulinostatic effect of peptide YY in isolated mouse
      pancreatic islets. We found that peptide YY (0.1 nmol/l-1 mumol/l) inhibited
      glucose (11.1 mmol/l)-stimulated insulin secretion from incubated isolated
      islets, with a maximal inhibition of approximately 70% observed at a dose of 1
      nmol/l (p < 0.001). Also in perifused islets the peptide (1 nmol/l) inhibited
      insulin secretion in response to 11.1 mmol/l glucose (p < 0.001). Furthermore,
      peptide YY inhibited glucose-stimulated cyclic AMP formation (by 67%, p < 0.05),
      and insulin secretion stimulated by dibutyryl cyclic AMP (p < 0.01). In contrast,
      the peptide was without effect both on the cytoplasmic Ca2+ concentration in
      dispersed mouse islet-cell suspensions as measured by the FURA 2-AM technique,
      and on insulin release in isolated islets, when stimulated by the protein kinase
      C-activator 12-O-tetradecanoyl phorbol 13-acetate. Finally, in pre-labelled
      perifused islets, peptide YY caused a small and transient increase in the 86Rb+
      efflux (p < 0.001), but only in the absence of extracellular Ca2+. We conclude
      that peptide YY inhibits glucose-stimulated insulin secretion from isolated mouse
      islets by inhibiting two different steps in the cyclic AMP cascade, that is, both
      the accumulation and the action of the cyclic nucleotide.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7806018
TI  - Hypertriglyceridaemia in subjects with normal and abnormal glucose tolerance:
      relative contributions of insulin secretion, insulin resistance and suppression
      of plasma non-esterified fatty acids.
AB  - Although plasma insulin and triglyceride concentrations are positively correlated
      in many studies, the relationships between insulin resistance, insulin secretion
      and hypertriglyceridaemia remain unclear. To study these associations, subjects
      between the ages of 40 and 64 were randomly selected from a general practice
      register and invited to attend for a standard oral glucose tolerance test for
      measurement of insulin, triglyceride and non-esterified fatty acid
      concentrations. The study comprised 1122 subjects who were not previously known
      to have diabetes and who completed the test. Using the World Health Organisation
      criteria, 51 subjects were classified to have non-insulin-dependent diabetes
      mellitus, 188 had impaired glucose tolerance and 883 subjects had normal glucose
      tolerance. Triglyceride concentrations in subjects with glucose intolerance were
      elevated compared to those in control subjects, even after adjustment for age,
      obesity and gender (p < 0.001 for subjects with diabetes and p < 0.01 for those
      with impaired glucose tolerance compared to normal subjects). In separate
      multiple regression analyses for males and females, the most important
      determinants of the plasma triglyceride concentration were the area under the non
      esterified fatty acid suppression curve (p < 0.001 in both genders) and the waist
      hip ratio (p < 0.001 for men and < 0.01 for women). The fasting insulin
      concentration was independently associated with triglyceride concentration in
      women only (p < 0.01). The most important determinant of the area under the non
      esterified fatty acid suppression curve in men was the 30-min insulin increment,
      a measure of insulin secretion, (p < 0.001) whereas for women age (p < 0.001) and
      the body mass index (p < 0.01) were the most important.

PMID- 7806019
TI  - The association of the insulin resistance syndrome with impaired glucose
      tolerance and NIDDM in the Japanese general population: the Hisayama study.
AB  - To elucidate the risk factors for initiating glucose intolerance, the relevant
      factors were explored in a cross-sectional survey conducted in a sample
      population aged 40-79 years old selected from a Japanese community, Hisayama,
      Japan in 1988. A 75-g oral glucose tolerance test was used to classify 1,073 men
      (72.5% of the entire population in the same age range) and 1,407 women (80.5%)
      into normal, impaired glucose tolerance and diabetes mellitus groups. In all age
      and sex groups with normal glucose tolerance, the sum of fasting and 2-h post
      load insulin values varied widely and demonstrated significant positive
      correlations with triglycerides, body mass index, waist-hip ratio, systolic and
      diastolic blood pressure, while it negatively correlated to HDL cholesterol (p <
      0.05). Insulin resistance was presumed to develop in normal glucose tolerance
      subjects with hyperinsulinaemia. The sum of the insulin concentrations,
      triglycerides, body mass index, waist-hip ratio and blood pressure levels was
      significantly associated with impaired glucose tolerance in all age and sex
      groups after adjustment for age (p < 0.05) and was also related to diabetes in
      either all or some age and sex groups, respectively (p < 0.05). It was shown that
      glucose intolerance in the general population was associated with the factors
      related to insulin resistance. These cross-sectional data, therefore, support the
      hypothesis that insulin resistance is the primary defect in the development of
      glucose intolerance in the Japanese general population. However, a further
      prospective study is still needed in order to confirm this hypothesis.

PMID- 7806020
TI  - Abnormal increases in urinary albumin excretion during pregnancy in IDDM women
      with pre-existing microalbuminuria.
AB  - We compared urinary albumin excretion during and after pregnancy in 30 insulin
      dependent diabetic (IDDM) women with normoalbuminuria and in 12 IDDM women with
      microalbuminuria (> 15 micrograms.min-1) prior to conception. There was a 6.7
      fold increase in the urinary albumin excretion up until the third trimester in
      the women with pre-existing microalbuminuria, compared with a 3.8-fold increase
      in the normoalbuminuric women. In both groups of patients the urinary albumin
      excretion reached a peak during the third trimester with 492 +/- 404
      micrograms.min-1 in the microalbuminuric women vs 43 +/- 36 micrograms.min-1 in
      the normoalbuminuric women (p < 0.0005). Two women from each of the groups
      developed eclampsia with diastolic blood pressure over 90 mm Hg, mild or moderate
      oedema and macroproteinuria. Four of the pregnant women with pre-existing
      microalbuminuria showed a transient nephrotic syndrome (33.3%) with protein
      excretion over 3 g in 24-h urine samples during the third trimester. In contrast,
      this was not observed in any of the normoalbuminuric women (p < 0.05). Within 12
      weeks after delivery the urinary albumin excretion rates dropped to the pre
      conception values in both patient groups. Renal function remained normal during
      pregnancy in both of the groups, with a physiological increase in creatinine
      clearance up until the third trimester (26% increase in the normoalbuminuric
      women vs 22% in the microalbuminuric women). In conclusion, the effect of
      pregnancy on the urinary albumin excretion in diabetic women with pre-existing
      microalbuminuria is an exaggeration of the increase of albuminuria in diabetic
      women with normoalbuminuria; normalization occurs within 12 weeks after delivery
      in all cases.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7806021
TI  - Presence and further development of retinal dysfunction after 3-year follow up in
      IDDM patients without angiographically documented vasculopathy.
AB  - Abnormalities in neuroretinal function may play a role in the development of
      diabetic retinopathy. The natural course of diabetic retinal dysfunction in a
      group of subjects with insulin-dependent diabetes mellitus and with no apparent
      microvascular alterations in the retina was followed-up with fluorescein
      angiography and a sensitive electrophysiological technique, i.e., steady-state
      focal electroretinogram at the macula, for 3 years. Before the beginning and
      throughout our study, strict glycaemic control was maintained by three or four
      daily insulin injections under careful monitoring. Analysis of macular
      electroretinogram provided information from different neural layers. At the first
      examination, functional activities of postreceptoral neurons were significantly
      decreased with respect to those of age-matched control subjects. Diabetic
      patients showed a functional loss of both ganglion cell (0.53 +/- 0.09 vs 0.42 +/
      0.11 microV; t = 5; p = 0.0001) and preganglion cell (0.51 +/- 0.13 vs 0.42 +/-
      0.14 microV; t = 2.8; p = 0.007) layers. Diabetes did not alter photoreceptor
      activity. After 3 years, dysfunction was significantly greater in the preganglion
      cell layer (0.28 +/- 0.11 microV; t = 6.3; p = 0.0001). Although in some patients
      further impairment of ganglion cell function was shown, no significant difference
      was found in 3 years. Photoreceptor function remained unaltered. No vascular
      abnormalities in the retina were noted after 3 years in this group of patients.
      Metabolic control was not correlated to functional changes. Our findings suggest
      that the middle retinal layer is the most sensitive physiological locus of
      progressive diabetes-induced dysfunction in the absence of angiographically
      documented abnormalities.

PMID- 7806022
TI  - Value of antibodies to GAD65 combined with islet cell cytoplasmic antibodies for
      predicting IDDM in a childhood population.
AB  - The value of a test for islet cell cytoplasmic antibodies together with a test
      for GAD65 antibodies to predict the subsequent development of diabetes over a
      period of 11.5 years was assessed in an open childhood population comprising
      2,805 individuals. A single serum sample was obtained from each individual
      between 1975 and 1977 and screened for islet cell cytoplasmic antibodies for
      which eight individuals were positive (0.29%). During the average follow-up
      period of 11.5 years, four of eight islet cell antibody positive and three islet
      cell antibody negative individuals developed clinical diabetes. Sera from all
      individuals, who were islet cell antibody positive and/or developed diabetes
      (total of 11) and from 100 randomly selected control subjects were analysed for
      GAD65 antibodies. Six of eight islet cell antibody positive individuals were
      GAD65 antibody positive including all four who subsequently developed IDDM.
      Furthermore, one of the three islet cell antibody negative individuals who
      developed IDDM was GAD65 antibody positive both in 1976 and in 1989. Thus, a
      positive test for GAD65 antibodies alone correctly predicted diabetes in five of
      seven children, who developed the disease. Only one of the children, who
      developed diabetes was positive for insulin autoantibodies and this individual
      was also positive for islet cell cytoplasmic antibodies and GAD65 antibodies. One
      of the 100 control subjects was positive for GAD65 antibodies (1%). The results
      suggest that a single GAD65 antibody test may have a higher sensitivity for
      predicting IDDM than a test for islet cell cytoplasmic antibodies, but that a
      combined positive test for both antibodies increases the specificity for
      predicting IDDM over a period of 11.5 years.

PMID- 7806023
TI  - Longitudinal analysis of somatic development in paediatric patients with IDDM:
      genetic influences on height and weight.
AB  - Normal growth and development, as well as the prevention of overweight, are major
      goals in the treatment of paediatric patients with insulin-dependent diabetes
      mellitus (IDDM). We therefore evaluated longitudinally the anthropometric
      measurements of height and weight, as well as bone age, in an unselected group of
      389 patients with IDDM treated at one institution. In order to identify genetic
      influences on these parameters, height and weight were determined in 186
      unaffected siblings and 177 pairs of parents. At diagnosis, patients were
      slightly taller than average (median z score: +0.37). During the subsequent
      course of diabetes, age-adjusted heights decreased progressively for the first 9
      years, catching up again after more than 10 years of diabetes. Bone ages were
      progressively retarded with increasing duration of diabetes. In 76 patients of 18
      years or older, median z-score for height was +0.30, not different from their
      unaffected siblings (median z-score: +0.22). The correlation with midparental
      height was identical for diabetic and nondiabetic siblings (r = 0.43). In
      contrast, children with diabetes were significantly heavier (z-score for weight:
      +0.74 compared to +0.34 in unaffected siblings; p < 0.002). Obesity developed
      primarily during and after puberty. We conclude that: 1) during the course of
      diabetes, longitudinal growth is temporarily reduced and maturation is delayed in
      children with diabetes compared to unaffected siblings. However, this effect of
      diabetes is transient and small compared to genetic influences on height in an
      individual child. 2) As a group, children with IDDM become significantly
      overweight, which is likely to increase the cardiovascular risk during adulthood.

PMID- 7806024
TI  - Differences in umbilical cord insulin and birth weight in non-diabetic
      pregnancies of women from different ethnic groups in New Zealand.
AB  - Many ethnic groups at high risk of non-insulin-dependent diabetes mellitus are
      hyperinsulinaemic by early adult life. This study assessed whether such
      hyperinsulinaemia is present at birth. Cross sectional comparisons of maternal
      biochemistry, umbilical cord biochemistry and neonatal anthropometry were made
      between one 'low risk' and three 'high risk' ethnic groups, without diabetes in
      pregnancy in Auckland, New Zealand. The study comprised 123 European, Polynesian
      (Maori and Pacific Islands) and Indian normal pregnancies. Indian mothers were
      the smallest, with the highest insulin and non-esterified fatty acid
      concentrations. Polynesian mothers were the most obese with a higher fructosamine
      concentration. From these pregnancies, Indian neonates were smaller, slimmer,
      with the highest cord triglyceride (0.6 mmol/l vs 0.4 mmol/l, p < 0.01), and
      lowest cord insulin concentrations (7.1 mU/l vs 8.6 mU/l (European), 9.2 mU/l
      (Polynesian), p < 0.05). Polynesian babies had a high cord insulin: C-peptide
      ratio (52.5 mU/nmol vs 44.4 mU/nmol (European), 44.1 mU/nmol (Indian), p = 0.05).
      Although reduced intrauterine growth may contribute to the excess of diabetes and
      heart disease in Indians, it cannot explain the excess of diabetes in
      Polynesians. Exposure to minor relative maternal hyperglycaemia in the mother and
      abnormal neonatal insulin handling (as demonstrated by the higher insulin: C
      peptide ratio) may be of long-term significance in Polynesians.

PMID- 7806026
TI  - Why is insulin not a risk factor for coronary heart disease?

PMID- 7806025
TI  - A gene in the HLA class I region contributes to susceptibility to IDDM in the
      Finnish population. Childhood Diabetes in Finland (DiMe) Study Group.
AB  - In Finland the haplotype A2, Cw1, B56, DR4, DQ8 is the third most common
      haplotype in insulin-dependent diabetic (IDDM) patients and has the highest
      haplotype-specific absolute risk for IDDM. Cw1, B56, DR4, DQ8 haplotypes
      containing HLA-A alleles other than A2 are infrequent in the population and are
      not associated with IDDM. Comparison of the A2 and non-A2 haplotypes at the DNA
      level showed that they were identical at HLA-B, -DR, and -DQ loci. Evidence that
      class I alleles confer susceptibility to IDDM was obtained from the two HLA-C, 
      B, -DR and -DQ haplotypes most frequently found in IDDM patients in Finland. A24,
      A3 and A2 on the Cw3, B62, DR4, DQ8 haplotype, and A28, A2 and A1 on the Cw7, B8,
      DR3, DQ2 were all found to be associated with IDDM. In Finland these seven
      haplotypes, including A2, Cw1, B56, DR4, DQ8, account for 33% of diabetic
      haplotypes and 10.3% of non-diabetic haplotypes (p < 0.00001). The contribution
      of the class I region to IDDM susceptibility was also apparent in those IDDM
      patients lacking the disease-predisposing class II alleles. Significantly more
      non-DR3/non-DR4 IDDM patients (47 of 55) possessed two of the IDDM-associated HLA
      A alleles compared to non-DR3/non-DR4 control subjects (40 of 58; p = 0.038).
      Moreover, IDDM patients confirmed by oligotyping as unable to form a 'diabetes
      susceptibility' DQ heterodimer, tended to possess two diabetes-associated HLA-A
      alleles (12 of 13) compared to control subjects (12 of 20; p = 0.056).

PMID- 7806028
TI  - Why can high insulin levels indicate a risk for coronary heart disease?

PMID- 7806027
TI  - Insulin resistance, compensatory hyperinsulinaemia, and coronary heart disease.

PMID- 7806029
TI  - The insulin resistance syndrome: the controversy is dead, long live the
      controversy!

PMID- 7806030
TI  - Acetazolamide inhibits basal and stimulated HCO3- secretion in the human proximal
      duodenum.
AB  - BACKGROUND/AIMS: Carbonic anhydrase activity plays a role in electrolyte
      transport in many tissues. This study examined the effect of the carbonic
      anhydrase inhibitor acetazolamide on human basal and prostaglandin E2- and acid
      stimulated duodenal mucosal bicarbonate secretion and transmucosal electrical
      potential difference. METHODS: Seven healthy volunteers participated in four
      separate experiments. The variables included oral acetazolamide vs. control test
      and, as agonists of bicarbonate secretion, either luminal acidification or
      luminal prostaglandin E2. The proximal 4 cm of the duodenum (i.e., the duodenal
      bulb) was isolated between balloons as previously described and perfused with an
      HCO(3-)-containing (24 mmol/L) balanced electrolyte glucose-containing (10
      mmol/L) solution. RESULTS: Acetazolamide treatment significantly decreased mean
      basal HCO3- secretion and basal transmucosal potential difference. After luminal
      acidification, duodenal mucosal bicarbonate increased significantly after both
      acetazolamide treatment (mean, 626; 95% CI, 91-1160 mumol.cm-1.h-1) and in the
      control tests (mean, 868; 95% CI, 652-1084 mumol.cm-1.h-1). However,
      acetazolamide treatment significantly decreased prostaglandin E2-stimulated HCO3-
      secretion from 461 (95% CI, 307-615) to 222 (95% CI, 121-324) mumol.cm-1.h-1.
      CONCLUSIONS: Duodenal mucosal carbonic anhydrase activity has an important
      function in the regulation of basal and prostaglandin E2-stimulated human
      duodenal mucosal bicarbonate transport.

PMID- 7806031
TI  - Human spasmolytic polypeptide is a cytoprotective agent that stimulates cell
      migration.
AB  - BACKGROUND/AIMS: Gastric epithelium is attacked by acid, pepsin, and ingested
      agents. When a mucosal lesion occurs, the defect is rapidly closed by cell
      migration. Because spasmolytic polypeptide is rapidly produced at sites of
      injury, we postulated that human spasmolytic polypeptide (hSP) was important in
      mucosal repair. Recombinant hSP was used to test this hypothesis. METHODS: The
      ulcer healing effect of various doses of hSP administered orally and
      subcutaneously was examined using an indomethacin (20 mg/kg) restraint rat model
      of gastric damage. Stability of hSP in gastrointestinal juice was determined
      using size-exclusion chromatography. The effect of hSP on migration of human
      colonic carcinoma cell lines HT29 and SW480 was determined using collagen gel
      invasion and wounded monolayer assays. Proliferation was assessed using
      [3H]thymidine incorporation and toluidine blue staining. RESULTS: Infusions of
      hSP at 25 and 50 micrograms.kg-1.h-1 subcutaneously decreased gastric damage by
      about 50% (P < 0.01) without changing acid secretion. Oral hSP was ineffective.
      hSP was stable in gastrointestinal juice. hSP stimulated migration of HT29 cells
      but did not affect proliferation and had no effect on SW480 cells. CONCLUSIONS:
      hSP may play a key role in the early stages of mucosal repair by stimulating the
      initial re-epithelialization by cell migration.

PMID- 7806032
TI  - Elevated c-yes tyrosine kinase activity in premalignant lesions of the colon.
AB  - BACKGROUND/AIMS: The cellular oncogene c-yes and its viral homologue v-yes (the
      transforming gene of Yamaguchi 73 and Esh avian sarcoma viruses) encode 62
      kilodalton, cytoplasmic, membrane-associated, protein-tyrosine kinases. For the
      related Src kinase, a close correlation exists between elevated kinase activity
      and cell transformation. Previously, we observed elevated Yes activity in many
      human colon carcinomas. Colonic neoplasia provides an opportunity to study tumor
      progression because most carcinomas arise from adenomas, which in turn arise from
      normal epithelia. The malignant potential of adenomas varies with size,
      histology, and degree of dysplasia. Large adenomas (> or = 2 cm) with villous
      architecture and severe dysplasia are most likely to develop carcinoma. METHODS:
      To determine whether Yes is activated in premalignant lesions of the colon, we
      measured its in vitro protein-tyrosine kinase activity in 21 colonic adenomas
      from 17 patients. RESULTS: Activity of Yes in adenomas at greatest risk for
      cancer was significantly greater (12- or 14-fold as measured by enolase or
      autophosphorylation, respectively) than activity in adjacent normal mucosa.
      Moreover, villous structure, large size (> or = 2 cm), or severe dysplasia
      correlated with elevated Yes activity. CONCLUSIONS: The activity of Yes is
      elevated in adenomas that are at greatest risk for developing cancer.

PMID- 7806033
TI  - Mechanism of colonic permeation of inulin: is rat colon more permeable than small
      intestine?
AB  - BACKGROUND/AIMS: Colonic epithelium is considered to be relatively tight. The
      colonic "pore" diameter is 6 A; therefore, colonic epithelium has generally been
      considered to be impermeable to hydrophilic probes with a cross-sectional
      diameter of > 6 A. This study examined whether rat colon is permeable to inulin,
      a large hydrophilic macromolecule having a molecular weight of 5000 g/mol and a
      cross-sectional diameter of 15 A (hydration diameter, 20 A). METHODS: The colonic
      permeation of inulin (10 mumol/L) in vivo was investigated by perfusion of rat
      colonic segments. RESULTS: There was significant colonic permeation of inulin,
      but tissue retention of inulin was low. The net colonic flux of inulin was
      strongly dependent on net water flux, showing a strong solvent drag effect.
      Addition of 16,16-dimethyl prostaglandin E2 decreased water flux with a
      corresponding decrease in inulin flux; this process seemed to be mediated by 5'
      cyclic adenosine monophosphate because both the phosphodiesterase inhibitor
      aminophylline and dibutyryl adenosine 5'-cyclic adenosine monophosphate decreased
      water and inulin flux in a parallel manner. Chenodeoxycholic and taurocholic
      acids decreased net mucosal-to-serosal water flux but increased inulin flux. The
      net colonic permeation rate of inulin was higher than the small intestinal
      permeation rate. CONCLUSIONS: Rat colon is permeable to inulin. The higher net
      colonic permeability may be caused by differences in mucosal surface,
      permselectivity, solvent drag effect, and differences in net water fluxes of the
      colon and small intestine.

PMID- 7806034
TI  - Relationships between the acidity and osmolality of popular beverages and
      reported postprandial heartburn.
AB  - BACKGROUND/AIMS: Although many beverages produce heartburn, the relationship
      between the acidity and osmolality of beverages and heartburn is unclear. The aim
      of this study was to relate the acidity and osmolality of beverages with their
      ability to cause heartburn. METHODS: We measured pH, total titratable acidity,
      and osmolality of 38 beverages in vitro and then correlated acidity and
      osmolality with the amount of heartburn reported by questionnaire in 394 people
      with heartburn. RESULTS: Among 17 citrus drinks and juices, titratable acidity
      correlated with reported heartburn scores (r = 0.65; P = 0.004). Soft drinks had
      the lowest pH readings of any beverages studied, and decreasing pH among soft
      drinks was correlated with reported heartburn scores (r = 0.82; P < 0.001).
      Alcoholic beverages (wines and beer), coffee, and (to a lesser extent) tea were
      associated with significant amounts of reported heartburn when compared with
      water. Milk was also associated with a modest amount of reported heartburn that
      was related to its fat content. Osmolality of beverages was unrelated to reported
      heartburn. CONCLUSIONS: High titratable acidity of citrus drinks and juices and
      low pH of soft drinks are associated with more reported heartburn. Our findings
      provide a foundation for dietary advice in patients with heartburn and reflux
      esophagitis.

PMID- 7806035
TI  - Severe portal hypertensive gastropathy and antral vascular ectasia are distinct
      entities in patients with cirrhosis.
AB  - BACKGROUND/AIMS: Whereas severe portal hypertensive gastropathy and gastric
      antral vascular ectasia (GAVE) have been separately defined in patients with
      cirrhosis, there is much confusion in the literature because they are both
      characterized by red spots at endoscopy. This prospective study compared
      clinical, biochemical, and pathological features of these syndromes. METHODS:
      Three groups of patients with cirrhosis and either GAVE (n = 14), severe portal
      hypertensive gastropathy (n = 14), or no gastric features at endoscopy (controls;
      n = 10) were included. RESULTS: No difference was found between patients with
      gastropathy and controls. Patients with GAVE presented with the following
      significant differences compared with other patients: a higher Child-Pugh score,
      a lower blood level of hemoglobin and gastrin, and a higher intestinal blood
      loss. At pathological examination, these patients more frequently had vascular
      ectasia (P = 0.04), spindle cell proliferation (P < 0.01), fibrohyalinosis (P =
      0.004), and Gilliam's score of > or = 2 (P < 0.05); thrombi were encountered only
      in patients with GAVE (P = 0.006). Using discriminant analysis, spindle cell
      proliferation and fibrohyalinosis were the only significant variables yielding a
      diagnostic accuracy of 85% for GAVE and gastropathy. CONCLUSIONS: GAVE and severe
      portal hypertensive gastropathy are two distinct entities.

PMID- 7806036
TI  - Growth factor and procollagen type I gene expression in human liver disease.
AB  - BACKGROUND/AIMS: Growth factors have been implicated in the pathogenesis of liver
      fibrosis, a major determinant of the clinical course of chronic liver disease.
      The aim of this study was to study the relationship of growth factor expression
      to inflammation and fibrosis in a variety of human liver diseases. METHODS: We
      studied by in situ hybridization the expression of transforming growth factor
      (TGF) beta 1, platelet-derived growth factor (PDGF) A and PDGF-B, and procollagen
      type I (pro-I) messenger RNAs (mRNAs) in liver diseases of various etiologies.
      RESULTS: Pro-I mRNA was expressed by mesenchymal cells at sites of inflammation
      and scarring, where TGF-beta 1 immunoreactivity was often found, and by
      perisinusoidal cells. TGF-beta 1 and PDGF-A mRNAs were expressed mainly by
      mononuclear cells and proliferating ductular cells. TGF-beta 1 mRNA was also
      expressed by perisinusoidal cells. PDGF-A gene expression was more common than
      that of PDGF-B. Pro-I and TGF-beta 1 expression correlated with both ductular
      proliferation and tissue inflammation, whereas PDGF-A and PDGF-B only correlated
      with ductular proliferation. CONCLUSIONS: Our data suggest that TGF-beta 1 and
      PDGF are involved in human liver inflammation and fibrosis. The expression of
      growth factor mRNAs in proliferating ductular cells may indicate a role for these
      cells in liver fibrogenesis and may help explain the pathophysiology of
      conditions such as biliary atresia progressing to fibrosis despite the absence of
      marked inflammation.

PMID- 7806037
TI  - Immunologic features and HLA associations in chronic viral hepatitis.
AB  - BACKGROUND/AIMS: Chronic viral hepatitis may have immunologic manifestations, and
      such features may reflect genetic predispositions. The aim of this study was to
      assess associations between immune manifestations and HLA-DR antigens. METHODS:
      Ninety-five patients were evaluated prospectively for immunologic features. A
      microlymphocytotoxicity technique was used to determine DR3, DR4, and A1-B8-DR3
      phenotypes. DR antigens were also determined by restriction fragment length
      polymorphism in 76 patients with chronic viral hepatitis and 80 normal subjects.
      RESULTS: Autoantibodies were found in 59 patients (62%), and concurrent
      immunologic diseases were found in 22 patients (23%). Patients with antinuclear
      antibodies had the A1-B8-DR3 phenotype more commonly than seronegative
      counterparts (26% vs. 6%; P = 0.02) and had DR3 positivity more frequently than
      normal subjects (41% vs. 18%; P = 0.03). In contrast, patients with concurrent
      immunologic diseases had DR4 positivity more commonly than patients without these
      findings (68% vs. 27%; P = 0.001) and normal subjects (68% vs. 30%; P = 0.003).
      CONCLUSIONS: Patients with chronic viral hepatitis commonly have autoantibodies
      and/or concurrent immunologic diseases. The expression of antinuclear antibodies
      is associated with the A1-B8-DR3 phenotype, and the presence of concurrent
      immunologic diseases is associated with the DR4 phenotype. In these instances,
      autoimmune expression may reflect a genetic predisposition that is facilitated by
      viral infection or is coincidental with it.

PMID- 7806038
TI  - Interferon alfa treatment of chronic hepatitis B: randomized trial in a
      predominantly homosexual male population.
AB  - BACKGROUND/AIMS: It has been suggested that human immunodeficiency virus (HIV)
      coinfection and male homosexuality predict poor response to interferon alfa
      therapy of chronic hepatitis B. The aim of this study was to examine the effect
      of HIV coinfection on the response of chronic hepatitis B virus (HBV) infection
      to interferon alfa therapy in a predominantly homosexual male population.
      METHODS: Fifty patients (82% male homosexuals, 50% HIV positive) with evidence of
      chronic HBV infection were randomized, stratified by HIV status, to undergo
      either treatment with interferon alfa (10 MU/m2 three times weekly for 12 weeks)
      or no treatment. Response was predefined as loss of serum HBV DNA, loss of
      hepatitis B e antigen, and the appearance of antibody to hepatitis B e antigen.
      HIV status and the interferon alfa-associated enzyme, 2',5'-oligoadenylate
      synthetase, were evaluated as potential predictors of response to therapy.
      RESULTS: Six treated patients responded with development of antibodies to
      hepatitis B e antigen (P < 0.05). HIV-positive patients were about one-fifth as
      likely to respond to interferon alfa therapy (relative risk, 0.22; 95% confidence
      interval, 0.03-1.78). Pretreatment alanine aminotransferase levels were
      significantly higher in responders than in nonresponders (P = 0.0005).
      Pretreatment 2',5'-oligoadenylate synthetase levels did not predict response.
      CONCLUSIONS: Interferon alfa, 10 MU/m2 three times weekly for 12 weeks, is
      effective in eradicating HBV replication in a predominantly homosexual male
      population not coinfected with HIV.

PMID- 7806039
TI  - Inhibition of hepatic metastases of human colon cancer in nude mice by a chimeric
      SF-25 monoclonal antibody.
AB  - BACKGROUND/AIMS: Hepatic metastasis is one of the most serious complications of
      human colon cancer. A murine-human chimeric SF-25 monoclonal antibody was
      prepared, and this construct recognizes a cell surface antigen highly present in
      human colon adenocarcinoma. METHODS: This study determined if the chimeric SF-25
      monoclonal antibody inhibits the outgrowth of hepatic metastases of human colon
      adenocarcinoma using an athymic nude mouse model. RESULTS: A single intravenous
      injection of chimeric SF-25 monoclonal antibody significantly inhibited the
      outgrowth of 5- and 7-day hepatic micrometastases (P = 0.0001 and 0.004,
      respectively, vs. untreated) and improved the survival of the animals. No
      detectable tumor was found in the liver when mice were treated by multiple
      injections of the antibody immediately after tumor cell grafting into the portal
      vein. In contrast, F(ab')2 fragments did not show antitumor effects, and the
      administration of natural killer cell or macrophage depleting agents (anti-asialo
      GM1 antibody and carrageenan, respectively) substantially inhibited the antitumor
      effects of chimeric SF-25 monoclonal antibody in vivo. CONCLUSIONS: Chimeric SF
      25 monoclonal antibody inhibits growth of hepatic metastasis of human colon
      cancer, and cell-mediated host immune mechanisms seem to be important for its in
      vivo antitumor activity.

PMID- 7806040
TI  - Membrane translocation and regulation of uridine diphosphate-glucuronic acid
      uptake in rat liver microsomal vesicles.
AB  - BACKGROUND/AIMS: Hepatic glucuronidation is quantitatively the most important
      conjugation reaction by which an array of endogenous compounds and xenobiotics
      undergo biotransformation and detoxification. The active site of the uridine
      diphosphate (UDP) glucuronosyltransferases, which catalyze glucuronidation
      reactions, has been postulated to reside in the lumen of the endoplasmic
      reticulum. The aim of this study was to characterize the process whereby UDP
      glucuronic acid (UDP-GlcUA), the cosubstrate for all glucuronidation reactions,
      is transported into microsomal vesicles. METHODS: The uptake process was analyzed
      using rapid filtration techniques, radiolabeled UDP-GlcUA, and rat liver
      microsomes. RESULTS: Uptake was saturable with respect to time and concentration,
      inhibited by 4,4'-diisothiocyanato-stilbene-2,2'-disulfonic acid and 4-acetamido
      4'-isothio-cyanatostilbene-2-2'-disulfonic acid, and was osmotically sensitive.
      Transport was stimulated by Mg2+ and guanosine triphosphate (50 mumol/L) but not
      guanosine 5'-O-(3-thiotriphosphate) or adenosine triphosphate. Luminal UDP-N
      acetylglucosamine (1 mmol/L) produced enhanced uptake of UDP-GlcUA (trans
      stimulation). In contrast to nucleotide sugar transport in the Golgi apparatus,
      trans uridine monophosphate and UDP did not alter UDP-GlcUA transport in
      microsomes, indicating distinct processes. CONCLUSIONS: These data provide
      unambiguous evidence for the existence of a unique, substrate-specific,
      regulated, carrier-mediated process that transports UDP-GlcUA into the lumen of
      hepatocyte microsomes. This transporter may regulate glucuronidation in vivo.

PMID- 7806041
TI  - Hepatic mitochondrial DNA deletion in alcoholics: association with microvesicular
      steatosis.
AB  - BACKGROUND/AIMS: Alcohol abuse may lead to microvesicular steatosis, a lesion
      ascribed to impaired mitochondrial function. Because alcohol abuse leads to
      reactive oxygen species in the hepatic mitochondria, it may damage mitochondrial
      DNA. The aim of this study was to look for the presence of the "common" 4977-base
      pair deletion in the hepatic mitochondrial DNA of alcoholic patients and age
      matched, nonalcoholic controls. METHODS: Hepatic DNA was subjected to two
      polymerase chain reactions that amplified non-deleted and deleted mitochondrial
      DNA, respectively. RESULTS: The deletion was found in 6 of 10 alcoholics with
      microvesicular steatosis, 2 of 17 alcoholic patients with macrovacuolar
      steatosis, but in none of 12 patients with acute alcoholic hepatitis, 11 patients
      with alcoholic cirrhosis, or 62 nonalcoholic patients of comparable ages with
      various other liver diseases or normal liver histology. In all patients with the
      deletion, restriction fragments of deleted mitochondrial DNA co-migrated with
      those of reference Pearson bone marrow-pancreas syndrome patients with the common
      mitochondrial DNA deletion. CONCLUSIONS: The common deletion is frequent in the
      hepatic DNA of alcoholic patients with microvesicular steatosis. Alcohol-induced
      mitochondrial DNA damage may contribute to the occurrence of this lesion in some
      alcoholics.

PMID- 7806042
TI  - Detection of antibodies against proteins modified by hydroxyethyl free radicals
      in patients with alcoholic cirrhosis.
AB  - BACKGROUND/AIMS: We have previously shown that hydroxyethyl free radicals
      produced during cytochrome P4502E1-mediated oxidation of ethanol covalently bind
      to microsomal proteins. The present study examined whether alkylation of proteins
      by hydroxyethyl radicals induces an immunologic response in alcoholic patients.
      METHODS: A microplate enzyme-linked immunosorbent assay was developed using as
      antigen human serum albumin or bovine fibrinogen reacted with chemically produced
      hydroxyethyl radicals. RESULTS: This assay showed that the sera of alcoholic
      cirrhotics contained both immunoglobulin (Ig) Gs and IgAs that recognized
      proteins modified by hydroxyethyl radicals, whereas practically no reaction was
      observed in the sera of healthy controls or cirrhotics without evidence of
      alcohol abuse. The reactivity of the sera from alcoholic patients was not
      influenced by the protein to which hydroxyethyl radicals were bound. The sera of
      alcoholic cirrhotics also contained antibodies directed against acetaldehyde
      modified albumin. However, the reaction of alcoholic sera with hydroxyethyl
      radical epitopes was not inhibited by increasing concentrations of acetaldehyde
      modified albumin produced under either reducing or nonreducing conditions.
      CONCLUSIONS: The results indicate that a new group of antigens that do not cross
      react with antibodies against acetaldehyde-derived epitopes is formed by the
      alkylation of protein by hydroxyethyl radicals and is involved in the development
      of immunologic reactions in alcoholic patients.

PMID- 7806043
TI  - Duodenal ferritin synthesis in genetic hemochromatosis.
AB  - BACKGROUND/AIMS: The molecular defect of genetic hemochromatosis (GH) is unknown.
      It is believed that low expression of duodenal ferritin in GH is caused by tissue
      or cell specific defect of ferritin synthesis. Our study was designed to
      ascertain whether the control of duodenal ferritin synthesis in GH was defective.
      METHODS: Expression at the single cell level of H and L ferritin messenger RNAs
      and protein and activity of the iron regulatory factor, which controls the
      translation of ferritin messenger RNA, were assessed in 43 duodenal biopsy
      specimens from individuals with GH, secondary hemochromatosis (SH), anemia, or
      normal iron balance. RESULTS: Signal for ferritin H and L subunit messenger RNAs
      was detected in both absorptive and nonabsorptive cells by in situ hybridization,
      but in 10 of 14 patients with untreated GH, the signal was lower than in patients
      with SH or normal subjects. However, immunostaining for ferritin protein
      documented a diffuse/cytoplasmic pattern, whereas a supranuclear/granular
      staining was found in normal subjects or patients with SH. The spontaneous
      activity of duodenal iron regulatory factor was consistently higher in patients
      with GH than in normal subjects or subjects with anemia or SH. CONCLUSIONS: In
      patients with GH, ferritin gene transcription is preserved in both absorptive and
      nonabsorptive intestinal cells. Low accumulation of ferritin is not caused by a
      defective control of ferritin synthesis but by low expression of ferritin
      messenger RNA and sustained activity of iron regulatory factor.

PMID- 7806044
TI  - Impaired response of activated mononuclear phagocytes to interleukin 4 in
      inflammatory bowel disease.
AB  - BACKGROUND/AIMS: In inflammatory bowel disease (IBD), peripheral monocytes and
      intestinal macrophages show an increased state of priming and activation. The aim
      of this study was to test the hypothesis that the response of IBD mononuclear
      phagocytes to the contrainflammatory cytokine interleukin (IL) 4 may be altered.
      METHODS: The in vitro secretion of proinflammatory cytokines (IL-1 beta, tumor
      necrosis factor alpha [TNF-alpha], and IL-1-receptor antagonist [IL-1ra]) by
      peripheral monocytes and by intestinal lamina propria mononuclear cells (LPMNCs)
      was assessed by enzyme-linked immunosorbent assay. In parallel, superoxide anion
      release, macrophage mannose receptor, and IL-4 receptor expression were
      investigated. RESULTS: IBD peripheral monocytes and intestinal LPMNCs in vitro
      secrete increased amounts of proinflammatory cytokines (IL-1 beta and TNF-alpha)
      with decreased IL-1ra/IL-1 beta ratios. IL-4 down-regulates proinflammatory
      cytokine (IL-1 beta and TNF-alpha) and superoxide anion secretion in a dose
      dependent manner. In contrast to normal and disease-specific controls, IBD
      peripheral monocytes and IBD intestinal LPMNCs show a diminished responsiveness
      to the inhibitory effect of IL-4. The IL-1ra/IL-1 beta ratios in normal monocytes
      are increased by IL-4, whereas in IBD monocytes low IL-1ra/IL-1 beta ratios
      persist after IL-4 treatment. IL-4-induced expression of macrophage mannose
      receptor, which is a molecule pivotal to macrophage-mediated host defense, again
      appeared to be impaired in IBD monocytes. CONCLUSIONS: IL-4-mediated regulation
      of mononuclear phagocyte effector functions is disturbed in IBD.

PMID- 7806045
TI  - Antibiotics prevent liver injury in rats following long-term exposure to ethanol.
AB  - BACKGROUND/AIMS: Kupffer's cells participate in alcohol-induced liver injury, and
      endotoxemia is observed in human alcoholics and in a rat model. This study
      evaluated the effect of reducing bacterial endotoxin production by intestinal
      sterilization on alcohol-induced liver injury. METHODS: Male Wistar rats were
      exposed to ethanol continuously for up to 3 weeks via intragastric feeding. The
      gut was sterilized with polymyxin B and neomycin. RESULTS: Fecal culture of stool
      samples from ethanol-fed rats treated with antibiotics showed virtually no growth
      of gram-negative bacteria. Endotoxin levels of 80-90 pg/mL in plasma of ethanol
      fed rats were reduced to < 25 pg/mL by antibiotics. Antibiotic treatment also
      completely prevented elevated aspartate aminotransferase levels and significantly
      reduced the average hepatic pathological score in rats exposed to ethanol. Oxygen
      tension on the surface of the liver measured in vivo was decreased significantly
      from control values of 48 +/- 1 to 39 +/- 1 mumol/L in ethanol-treated rats. This
      hypoxia was prevented by treatment with antibiotics. Moreover, the increase in
      rates of ethanol elimination due to long-term ethanol treatment was prevented by
      antibiotic treatment. CONCLUSIONS: Intestinal sterilization prevented alcohol
      induced liver injury in the rat, supporting the idea that hypermetabolism and
      consequent hypoxia caused by activation of Kupffer's cells by endotoxin is
      involved in the mechanism.

PMID- 7806046
TI  - Protracted viremia during acute sporadic hepatitis E virus infection.
AB  - BACKGROUND/AIMS: Hepatitis E virus (HEV) is associated with epidemic and sporadic
      hepatitis in developing countries. The disease is largely self-limited with no
      long-term sequelae. The source of HEV for maintenance of the disease in an
      endemic area is unknown. This study investigated the occurrence and duration of
      viremia in patients with acute sporadic HEV infection. METHODS: In 26 of 37
      patients with sporadic acute non-A, non-B viral hepatitis, HEV infection was
      diagnosed based on positivity for immunoglobulin M anti-HEV and/or presence of
      viremia as shown by reverse-transcription polymerase chain reaction. In 4
      patients, fecal samples were analyzed for presence of virus using polymerase
      chain reaction. Multiple samples were studied at varying times in 20 patients.
      RESULTS: Viremia was detected in 19 of 26 patients. Two patients had viremia in
      the absence of immunoglobulin M anti-HEV. Four patients had protracted viremia of
      45-112 days' duration. One patient showed fecal virus shedding up to the 52nd day
      of illness. CONCLUSIONS: Protracted viremia and prolonged fecal shedding of HEV
      were shown in a small group of patients. These patients may serve as temporary
      virus carriers responsible for continuous contamination of the sewage water.

PMID- 7806047
TI  - Sphincter of Oddi dysfunction caused by an ampullary neoplasm.
AB  - The case of a 50-year-old man with abdominal pain and abnormal liver test results
      is described. Endoscopic retrograde cholangiopancreatography with manometric
      studies showed biliary dilatation, poor ductal drainage, and sphincter of Oddi
      dysfunction. Clinical and radiographic clues suggested the possibility of an
      ampullary lesion; a small ampullary adenoma was detected after endoscopic
      sphincterotomy, and ampullary carcinoma was found in the operative specimen.
      Malignancy can cause sphincter dysfunction not only in the esophagus (as
      pseudoachalasia) but in the ampulla of Vater as well.

PMID- 7806048
TI  - Human immunodeficiency virus 1-associated necrotizing cholangitis caused by
      infection with Septata intestinalis.
AB  - A 30-year-old man with acquired immunodeficiency syndrome developed human
      immunodeficiency virus 1-related cholangiopathy with atypical radiographic
      features showing extensive hepatobiliary involvement. Extended clinical
      evaluation, including endoscopic retrograde cholangiopancreatography, and the
      results of both ultrasonic- and computed tomographic-guided liver biopsies failed
      to provide a diagnosis. A laparoscopic needle biopsy of a single 3-cm, firm, tan
      lesion on the anterior surface of the liver showed severe necrotizing
      cholangitis. Special stains showed numerous microsporidial spores within the
      regions of granulomatous inflammation and prominent necrosis. Electron
      micrographic findings were characteristic of Septata intestinalis, a newly
      recognized microsporidial species that disseminates from the intestinal tract and
      is associated with invasive pathology.

PMID- 7806049
TI  - Liver cell necrosis: cellular mechanisms and clinical implications.
AB  - Based on our current understanding, we have developed a provisional model for
      hepatocyte necrosis that may be applicable to cell necrosis in general (Figure
      6). Damage to mitochondria appears to be a key early event in the progression to
      necrosis. At least two pathways may be involved. In the first, inhibition of
      oxidative phosphorylation in the absence of the MMPT leads to ATP depletion, ion
      dysregulation, and enhanced degradative hydrolase activity. If oxygen is present,
      toxic oxygen species may be generated and lipid peroxidation can occur.
      Subsequent cytoskeleton and plasma membrane damage result in plasma membrane bleb
      formation. These steps are reversible if the insult to the cell is removed.
      However, if injury continues, bleb rupture and cell lysis occur. In the second
      pathway, mitochondrial damage results in an MMPT. This step is irreversible and
      leads to cell death by as yet uncertain mechanisms. It is important to note that
      MMPT may occur secondary to changes in the first pathway (e.g. oxidative stress,
      increased Cai2+, and ATP depletion) and that all the "downstream events"
      occurring in the first pathway may result from MMPT (e.g., ATP depletion, ion
      dysregulation, or hydrolase activation). Proof of this model's applicability to
      cell necrosis in general awaits further validation. In this review, we have
      attempted to highlight the advances in our understanding of the cellular
      mechanisms of necrotic injury. Recent advances in this understanding have allowed
      scientists and clinicians a better comprehension of liver pathophysiology. This
      knowledge has provided new avenues of therapy and played a key role in the
      practice of hepatology as evidenced by advances in organ preservation.
      Understanding the early reversible events leading to cellular and subcellular
      damage will be key to prevention and treatment of liver disease. Hopefully,
      disease and injury specific preventive or pharmacological strategies can be
      developed based on this expanding data base.

PMID- 7806050
TI  - Bone disease in cholestatic liver disease.
AB  - Osteopenia in the form of osteoporosis is a common clinical problem associated
      with chronic cholestatic liver disease, and clinical morbidity from atraumatic
      fractures is increasing as more patients with PBC and PSC undergo successful
      liver transplantation. In the absence of symptomatic fractures, the clinical
      diagnosis may not be evident and must be sought by specific means to assess bone
      mineral density. The clinical problem has now been defined, but much remains
      unknown, from etiologic mechanisms to effective therapies. At present, it seems
      reasonable to provide aggressive supportive therapy in an attempt to maximize
      skeletal well-being until more effective therapies for osteopenia become
      available.

PMID- 7806051
TI  - Interleukin-4 hyporesponsiveness in inflammatory bowel disease: immune defect or
      physiological response?

PMID- 7806052
TI  - Nerves and cholera secretion.

PMID- 7806053
TI  - Ambulatory recording of lower esophageal sphincter pressure: adding the missing
      link.

PMID- 7806054
TI  - Src family of tyrosine kinases: a role of c-yes in colon carcinogenesis?

PMID- 7806055
TI  - Management of patients with gastric carcinoid tumors.

PMID- 7806056
TI  - Alcoholic pancreatitis: unraveling the mystery.

PMID- 7806057
TI  - You may not be what you eat.

PMID- 7806058
TI  - Economic heartburn: average cost-effectiveness and gastroesophageal reflux
      disease.

PMID- 7806059
TI  - Ghosts in the stomach: may dead cells protect living ones.

PMID- 7806060
TI  - Regulation of hepatocellular Na+/H+ exchange.

PMID- 7806061
TI  - Cholera toxin-induced small intestinal secretion has a secretory effect on the
      colon of the rat.
AB  - BACKGROUND/AIMS: Little information is available on the role of colon during
      small intestinal secretion. The aim of this study was to examine the effects of
      secretory changes in the small intestine on the colonic transport of electrolytes
      and water in vivo. METHODS: The jejunum and colon of the rat were perfused in
      vivo simultaneously but separately, and jejunal secretion was induced by exposing
      the jejunum to cholera toxin, 8-bromo-cyclic guanosine monophosphate, or
      hyperosmolarity. RESULTS: Jejunal perfusion with a hyperosmolar mannitol solution
      (600 mOsm/L) or with 8-bromo-cyclic guanosine monophosphate (0.5 mmol/L) resulted
      in net secretion of water in the jejunum but did not affect the baseline rate of
      water transport in the colon. On the contrary, addition of cholera toxin (1
      microgram/loop) to the jejunal segment not only induced a significant local
      secretory change but also resulted in a similar change in the colon, which was
      not exposed to cholera toxin. The intestine was transected immediately below the
      jejunum, thus interrupting the anatomical continuity of the enteric nervous
      system. This procedure eliminated the distant secretory effect of cholera toxin,
      thus allowing the conclusion that the enteric nervous system is involved in the
      distant propagation of the local secretion induced by cholera toxin. CONCLUSIONS:
      Cholera toxin, but not other secretagogues, triggers a secretory response that is
      not only local but also extends to distal segments via the enteric nervous
      system.

PMID- 7806063
TI  - Two endothelin receptors (ETA and ETB) expressed on circular smooth muscle cells
      of guinea pig cecum.
AB  - BACKGROUND/AIMS: The functional receptors for endothelin (ET) in colonic smooth
      muscle are still unknown. This study investigated the expression of ET receptors
      in isolated circular smooth muscle cells of guinea pig cecum. METHODS: Inhibition
      of 125I-ET-1 binding was examined using unlabeled ET-1, ET-2, ET-3, sarafotoxin
      6c (S6c), and ETA antagonists. Expression of the ET-receptor message was
      investigated using reverse-transcription polymerase chain reaction. The
      contractile potency of the ET family and the inhibitory effect of ETA antagonists
      on ET-1-induced contraction were also investigated. RESULTS: Unlabeled ET-1, ET
      2, and ET-3 inhibited the specific binding of 125I-ET-1 in a concentration
      dependent manner, but the inhibitory effect of ET-3 was smaller than those of ET
      1 and ET-2. At a 10(-6) mol/L concentration of S6c, the specific binding of 125I
      ET-1 was 24.7%. S6c had clearly reached maximal inhibition. Abundant polymerase
      chain reaction products for both the ETA and the ETB message were observed. ET-1
      and ET-2 showed similar contractile potency, but ET-3-induced and S6c-induced
      contractions were significantly less potent than the ET-1-induced contraction. A
      significant response to S6c was obtained at a concentration as low as 10(-10)
      mol/L. The ETA antagonists BQ-123 and FR 139317 significantly inhibited ET-1
      induced contraction. CONCLUSIONS: The results show a direct contractile effect of
      ETs on circular smooth muscle of guinea pig cecum and the presence of both ETA-
      and ETB-receptor subtypes.

PMID- 7806062
TI  - Monocyte-chemoattractant protein 1 gene expression in intestinal epithelial cells
      and inflammatory bowel disease mucosa.
AB  - BACKGROUND: Monocyte-chemoattractant protein 1 (MCP-1) activates macrophages and
      increases the migration of monocytes into tissue during inflammation. It was
      hypothesized that MCP-1 expression is involved in intestinal inflammation.
      METHODS: MCP-1 protein was detected by immunohistochemistry and
      immunoprecipitation. Biological activity of MCP-1 was assessed using a
      chemotactic assay. MCP-1 messenger RNA (mRNA) levels were measured by
      quantitative reverse-transcription polymerase chain reaction. RESULTS: In normal
      mucosa, MCP-1 was predominantly present in surface epithelium. In contrast,
      inflamed mucosa from patients with ulcerative colitis or Crohn's disease
      contained multiple cells immunoreactive for MCP-1, including spindle cells,
      mononuclear cells, and endothelial cells. Furthermore, MCP-1 mRNA expression was
      markedly increased in inflamed intestinal biopsy specimens from patients with
      inflammatory bowel disease. MCP-1 was detected in isolated intestinal epithelial
      cells and in conditioned media from Caco-2 cells. Caco-2 cell-conditioned media
      stimulated monocyte chemotaxis activity that was inhibited by anti-MCP-1
      antibodies. Constituitive MCP-1 mRNA levels in Caco-2 cells were up-regulated by
      interleukin 1 beta and down-regulated by dexamethasone. CONCLUSIONS: In addition
      to lamina propria macrophages, endothelial cells, and spindle cells, intestinal
      epithelial cells are able to produce MCP-1. MCP-1 is expressed constitutively in
      the intestinal colonic mucosa and is up-regulated during inflammation.

PMID- 7806064
TI  - Endogenous nitric oxide modulates ethanol-induced gastric mucosal injury in rats.
AB  - BACKGROUND/AIMS: Endothelium-derived relaxing factor regulates vascular tone via
      vasodilation. The relative contribution of endogenous nitric oxide to the
      pathophysiology of ethanol-induced gastric mucosal microcirculatory disturbances
      was investigated in anesthetized rats. METHODS: Macroscopic and microscopic
      gastric mucosal damage and gastric mucosal hemodynamics including blood flow and
      hemoglobin oxygen saturation (ISO2) were assessed by pretreatment with a specific
      NO synthase inhibitor, N omega-nitro-L-arginine (L-NNA), before and after
      intragastric administration of ethanol. RESULTS: Pretreatment with L-NNA
      significantly increased macroscopic (7.7-fold) and microscopic damage caused by
      30% ethanol. Concurrent administration of L-arginine, but not D-arginine,
      significantly reduced the increase in mucosal damage. Similar results were
      obtained with 60% ethanol. Pretreatment with L-NNA decreased both mucosal blood
      flow and ISO2 in the basal period and enhanced decreases in both mucosal blood
      flow (2.7-fold) and ISO2 (4.3-fold) induced by 30% ethanol compared with
      controls. Concurrent administration of L-arginine, but not D-arginine,
      significantly inhibited the effect of L-NNA on blood flow and ISO2 in the basal
      period as well as after intragastric administration of 30% ethanol. CONCLUSIONS:
      Endogenous NO modulates ethanol-induced gastric mucosal injury through the
      regulation of gastric mucosal microcirculation.

PMID- 7806065
TI  - Expression of interleukin 8 and CD54 by human gastric epithelium after
      Helicobacter pylori infection in vitro.
AB  - BACKGROUND/AIMS: Helicobacter pylori is associated with neutrophil infiltrates,
      although the mechanism of their recruitment is only partially defined. The aim of
      the study was to determine if Kato III, a human gastric epithelial cell line,
      expressed cytokines and the intercellular adhesion molecule 1 (ICAM-1), which
      could contribute to the initiation of inflammation during infection with H.
      pylori. METHODS: Kato III cells were stimulated with H. pylori and were examined
      for evidence of infection, cytokine production, and the expression of ICAM-1.
      RESULTS: The expression of interleukin 8 messenger RNA and immunoreactive protein
      by Kato III cells was significantly increased over constitutive levels within 3
      hours of infection with H. pylori. Infected Kato III supernatants activated
      neutrophils as evidenced by increased CD11b/CD18 and decreased L-selectin that
      could be blocked by anti-interleukin 8. In contrast, Campylobacter jejuni,
      lipopolysaccharide, killed H. pylori, and supernatants from cultures of H. pylori
      did not increase interleukin 8. Interleukins 2 and 6; interferons alfa, beta, and
      gamma; and tumor necrosis factor were not produced by resting or H. pylori
      stimulated Kato III cells. In addition to producing interleukin 8, Kato III
      constitutively expressed surface ICAM-1, which acts as an intercellular adhesion
      molecule for neutrophils. CONCLUSIONS: Our results indicate that H. pylori
      stimulates the gastric epithelium to initiate inflammation and neutrophil
      recruitment and activation.

PMID- 7806066
TI  - Mechanisms of gastroesophageal reflux in ambulant healthy human subjects.
AB  - BACKGROUND/AIMS: Investigation of the motor events underlying gastroesophageal
      reflux has largely been confined to resting, recumbent subjects. The motor events
      associated with reflux during physical activity remain unknown. The aim of this
      study was to investigate the patterns of lower esophageal sphincter (LES)
      function underlying reflux in healthy subjects and the effect of exercise and
      physical activity on reflux mechanisms. METHODS: LES pressure was recorded with a
      perfused sleeve sensor in 10 healthy subjects; intraluminal transducers recorded
      pressure in the stomach, esophagus, and pharynx, and pH was recorded 5 cm above
      the LES. Signals were stored in a portable data-logger. Recordings were made for
      24 hours, including moderate physical activity, periods of rest and sleep,
      standardized meals, and standardized exercise. RESULTS: Most reflux episodes (81
      of 123; 66%) occurred in the 3 hours after food intake; only 2 episodes occurred
      during exercise. LES pressure was < or = 3 cm H2O in 79% of reflux episodes.
      Transient LES relaxation was the mechanism of reflux in 82% of episodes,
      irrespective of activity or body position, whereas swallow-related LES
      relaxations accounted for 13% and persistently absent LES pressure accounted for
      1%. Straining occurred in only 20% of episodes. CONCLUSIONS: In ambulant healthy
      subjects, accurate continuous recording of LES function is possible, reflux
      usually occurs during transient LES relaxations, and straining is not a major
      factor in the induction of reflux.

PMID- 7806068
TI  - Full analytical description of graviosmotic volume flows.
AB  - A full analytical description of graviosmotic volume flows is presented. This was
      done with the use of theoretical models earlier developed on the basis of
      interferometric studies of graviosmotic systems. The description includes both
      stationary and non-stationary graviosmotic flows induced with solutions whose
      density decreases as well as increases with increasing concentration. The
      obtained equations that describe the fluxes may prove especially useful in
      studies on water transport in plants which occurs by graviosmotic mechanisms.

PMID- 7806069
TI  - Vanadate and fluoride activate red cell Na+ permeability by different mechanism.
AB  - Fluoride and vanadate are known to induce the Ca(2+)-dependent K+ efflux. We
      found that both agents concomitantly induced the Ca(2+)-dependent 22Na+ influx.
      The extent of the Ca(2+)-dependent 22Na+ influx induced by vanadate was very
      small in human red blood cells but clearly visible in guinea-pig red blood cells.
      The effect of fluoride has been studied in human red blood cells only. The 22Na+
      influx induced by vanadate was inhibited by amiloride but was resistant to
      tetrodotoxin, whereas that induced by fluoride was resistant to amiloride but
      sensitive to tetrodotoxin. The effects of inhibitors indicate that vanadate
      activates the Na/H antiporter and that fluoride opens a tetrodotoxin-sensitive
      Na+ channel in red blood cells in the Ca(2+)-dependent manner. The results also
      indicate that both agents activate the Ca(2+)-dependent Na+ permeabilities by
      unknown auxiliary mechanisms.

PMID- 7806067
TI  - Epidermal growth factor is digested to smaller, less active forms in acidic
      gastric juice.
AB  - BACKGROUND/AIMS: Epidermal growth factor (EGF) is present in gastric juice and
      has potent mitogenic properties. The stability of EGF in gastric juice under
      various physiological and pathophysiological conditions was examined. METHODS:
      Recombinant human EGF1-53 was incubated with HCl containing pepsin. We also
      determined the forms of EGF present in the gastric juice of patients under basal
      conditions, patients taking the acid suppressant omeprazole, patients with
      achlorhydria, and volunteers undergoing intragastric neutralization with NaHCO3
      (n = 6 per group). Samples were analyzed using mass spectroscopy and/or high
      pressure liquid chromatography followed by radioimmunoassay. The effect of acid
      and pepsin digestion on EGF bioactivity was determined using an in vitro
      hepatocyte bioassay and an in vivo cytoprotection assay in the rat stomach.
      RESULTS: EGF1-53 was digested to the EGF1-49 and EGF1-46 forms in all samples
      containing pepsin when the pH was < 4. In gastric juice samples with pH > 4, the
      proportion of intact EGF increased to about 60%. For both methods of bioassay,
      intact EGF1-53 was about 3-4 times as potent as acid and pepsin-treated EGF.
      CONCLUSIONS: EGF is produced in the 1-53 form but is rapidly cleaved to smaller,
      less active forms in acidic gastric juice. In contrast, only a small proportion
      of the EGF is cleaved if the pH is maintained above 4. This mechanism may be
      relevant to the healing process of acid suppressants.

PMID- 7806070
TI  - Isolation of plant cytochrome P-450 and NADPH: cytochrome P-450 reductase from
      tulip bulbs (Tulipa fosteriana L.) oxidizing xenobiotics.
AB  - Cytochrome P-450 and NADPH: cytochrome P-450 reductase were solubilized by
      detergents from microsomal fraction of tulip bulbs Tulipa fosteriana L. and
      purified to electrophoretic homogeneity. The purification was achieved by anion
      exchange column chromatography, hydroxyapatite-column chromatography and affinity
      chromatography. The two enzyme showed relative molecular weights of about 54,200
      and 77,600 for cytochrome P-450 and NADPH: cytochrome P-450 reductase,
      respectively. The purified enzymes were characterized by their absorption spectra
      and by kinetic characteristics. The interaction with endogeneous as well as
      exogenous substrates was studied by differential spectroscopy. Both enzymes in
      the presence of dilauroyl phosphatidylcholine and NADPH were able to oxidize
      xenobiotics (N-nitroso-N-methylaniline and N-nitroso-N-dimethylamine) in the
      reconstitution experiments.

PMID- 7806071
TI  - Oxidative damage of the membrane lipids after electroporation.
AB  - Electric field pulses used for cell manipulation can cause irreversible cell
      damage. The mechanisms of the processes leading to such cell damage are very
      complicated. Our work demonstrated that exponential electric pulses with
      intensity of 2-7.5 kV/cm and duration of 5.2 ms were able to initiate
      peroxidation of fatty acid emulsions, liposomal membranes, red blood and Ehrlich
      ascite tumor cells. Electric pulses-induced peroxidation of erythrocyte membranes
      was followed by hemolysis. The electric treatment caused damage of E. coli
      membrane lipids which was accompanied by decreased cell survival. All these
      effects depended on field intensity. A relatively good correlation between pulse
      induced peroxidation of erythrocyte membranes and hemolysis was observed. These
      results suggest that free radical mediated processes as lipid peroxidation and/or
      lipid degradation or fragmentation may be possible causes for electric pulses
      induced irreversible cell damage.

PMID- 7806072
TI  - Alteration of tension response to stretch with spontaneous contraction frequency
      in the guinea pig taenia coli and stiffness-work characteristics.
AB  - Previously we developed a data acquisition procedure to measure the tension
      responses of smooth muscles during their spontaneous contraction. This study was
      undertaken to determine whether the time course of the tension responses to
      stretches was altered with the ongoing spontaneous contractions. In addition, the
      stiffness, phase and work characteristics were evaluated from the tension
      responses in order to see how these characteristics were affected by the changes
      in the tension responses. The tension responses of the spontaneously contracting
      taenia coli to stretches had four phases. However, the latencies of the phases
      changed with the type of the spontaneous contractions during which the
      measurement was carried out. In the responses recorded during the slow
      spontaneous contractions (40-70 s), the second phase reached the minimum at 2.26
      +/- 1.12 s and the third phase had the peak tension at 9.56 +/- 3.08 s. These
      latencies were 0.89 +/- 0.30 s and 3.91 +/- 1.10 s, respectively, when the
      experiments were undertaken during high frequency contractions (10-30 s).
      Besides, the maxima and minima in the stiffness, phase and work characteristics
      were also shifted to higher frequencies as the spontaneous contraction became
      faster. Work had a positive peak around 0.03 Hz for the slowly contracting taenia
      coli. The peak shifted to 0.1 Hz when the taenia coli contracted at higher
      frequency. The results show that the time course of the tension responses is
      determined by the contractile state of the taenia coli.

PMID- 7806073
TI  - Interactions of cells, cytokines, and mediators in bronchial asthma.

PMID- 7806074
TI  - The impact of pharmacologic therapy on the costs of asthma.
AB  - Continued growth of health care as a major sector of the U.S. economy has brought
      concern about whether health care services can be made more efficient and
      effective. Much of this concern is global in nature, relating to comprehensive
      issues in preventive and therapeutic services. Yet, examination of specific
      conditions provides insight into explicit approaches to achieving more effective
      care. The purpose of this report is to provide an overview of one health
      condition, asthma, and will 1) introduce the health economic concepts that define
      the costs of illness for asthma; 2) discuss the outcomes that are relevant to
      effective asthma management from a health systems perspective; 3) review the
      concepts underlying the study of cost-effectiveness of asthma care; and 4)
      examine the existing and emerging literature on the cost-effectiveness of asthma
      care.

PMID- 7806075
TI  - Anti-inflammatory drugs for treatment of asthma: mechanisms of action.

PMID- 7806076
TI  - Spontaneous cerebrospinal fluid rhinorrhea with associated sinusitis and allergic
      rhinitis.
AB  - The entity of spontaneous cerebrospinal fluid rhinorrhea is a rare condition that
      presents a special challenge to the practicing allergist. Delayed diagnosis can
      be associated with significant morbidity and mortality. We describe two cases of
      this condition occurring in association with allergic rhinitis and sinusitis. The
      presentation and management of these cases is described. A high index of
      suspicion for this condition should be maintained in all patients who present
      with profuse and often unilateral rhinorrhea.

PMID- 7806077
TI  - Management of sinusitis: current perspectives.

PMID- 7806078
TI  - The precipitation of symptoms by common foods in children with atopic dermatitis.
AB  - Atopic dermatitis (AD) is a chronic and disabling condition that has a major
      impact on financial and social resources of the individual and the community. Its
      incidence is increasing dramatically, and no cure is available. Pharmacological
      treatment is only partially effective. The evidence that diet plays a role in
      children with atopic dermatitis is now irrefutable. Prophylactic measures can
      prevent or limit the development of AD, and partially restricted diets can modify
      the disease's course or severity. This study reports the reactions to various
      foods as perceived by parents of 112 children affected by AD. It demonstrates
      that many foods exacerbate AD and that reactions are caused by two distinct
      groups of food. The commonest triggers of cutaneous symptoms are tomatoes,
      oranges, sweets, pineapple, chocolate, and softdrinks preserved with sulfur
      dioxide. These foods result in symptoms in 30% to 49% of the children. The
      traditional IgE reaction type foods, namely egg, fish, milk, and peanut, resulted
      in reactions in 14% to 25% of the children, and with many non-cutaneous symptoms.
      The study further shows that allergen avoidance measures are not practiced in our
      community, and that sound advice is not often proffered. Practical advice on
      prophylactic dietary preventative measures and dietary management of children
      with atopic dermatitis is presented.

PMID- 7806079
TI  - Cross-reactivity of food allergens in latex allergy.
AB  - Allergy resulting from exposure to latex proteins has been reported with
      increasing frequency in certain patient and occupational groups. Patients with
      latex allergy demonstrate cross-reactivity with some food allergens. Although
      amino acid homology of a few polypeptides from food and latex have been reported,
      no information is available comparing food and latex allergens. In the present
      study, we have obtained antibody from latex-sensitive patients by affinity
      absorption with various food and latex allergen extracts. The antibodies were
      then evaluated for reactivity with various antigens by ELISA. The results
      indicated that IgE cross-reactivity existed between different latex and food
      antigens. Hence, care should be exercised during evaluation of patients, as the
      clinical response may not be directed to the primary sensitizing antigen and may
      represent cross-reactivity of antigens.

PMID- 7806081
TI  - Food ingredient labeling: how many ways can wheat be spelt?

PMID- 7806080
TI  - Spelt is wheat.

PMID- 7806082
TI  - Recipient of AAAI Lifetime Achievement Award.

PMID- 7806083
TI  - Controversies on Hodgkin's disease and anaplastic large cell lymphoma.
      Hematopathology Study Group of the Societa Italiana di Anatomia Patologica.
AB  - Just one year ago the Italian Society of Pathology (S.I.A.P.) created a Study
      Group which included members of the most active Italian hematopathology teams.
      Prof. Pasquale Calapso was asked to chair the Group and Prof. Stefano Pileri to
      take care of secretarial duties. The aim of the Group is to spread
      hematopathologic knowledge among young pathologists and to promote activities
      that can contribute to updating Italian pathologists on topics of both
      speculative and diagnostic interest. The first Workshop of the S.I.A.P.
      Hematopathology Group was held at the Palazzo dei Congressi in Bologna, November
      20, 1993. About 150 pathologists from all over Italy took part in the meeting,
      which consisted of two sections devoted to: a) discussion of the boundaries
      between Hodgkin's disease and non-Hodgkin's lymphomas, and b) a case seminar
      illustrating the impact of immunohistochemistry in the diagnosis of bone-marrow
      biopsy. The first section included 5 presentations and a Round Table chaired by
      Prof. Luciano Fiore-Donati. Below, the contributors to this section summarize the
      content of their presentations, which were aimed at answering specific questions
      the Organizers had put to them.

PMID- 7806084
TI  - In vitro sensitivity of human erythroid progenitors to hemopoietic growth
      factors: studies on primary and secondary polycythemia.
AB  - BACKGROUND: Primary proliferative polycythemia is a clonal disease characterized
      by excessive hemopoiesis and associated with a lower than normal erythropoietin
      plasma level; in vitro colony studies may reveal increased sensitivity of the
      abnormal clone to hemopoietic growth factors. MATERIALS AND METHODS: We studied
      the in vitro formation of erythroid colonies (BFU-E derived clone) in cultures
      set up with a serum-free medium and containing Epo, interleukin 3 (IL-3) and stem
      cell factor (SCF), in various combinations. The clonogenic test was performed by
      plating non adherent mononuclear cells from the peripheral blood of normal
      subjects and from patients with PPP and secondary polycythemia (SP). RESULTS: SCF
      is a major amplifier of erythroid colony growth, in the presence of Epo; in
      cultures from PPP patients, however, the presence of SCF, in addition to Epo,
      enhances colony formation at about the same rate as in cultures from normal
      subjects. When SCF is omitted, the presence of even modest amounts of Epo and IL
      3 is sufficient to obtain a statistically significant difference between colony
      formation from PPP patients on the one side, and SP patients and normal subjects
      on the other. CONCLUSIONS: Our results show that in vitro culture studies may
      contribute an additional diagnostic criterion for distinguishing between PPP and
      SP in uncertain cases. It is also possible that hypersensitivity to
      erythropoietic factors may play a role in the pathogenetic mechanism of primary
      proliferative polycythemia.

PMID- 7806085
TI  - Molecular and biochemical data on some glucose-6-phosphate dehydrogenase variants
      from southern Sardinia.
AB  - BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD; E.C.1.1.1.49) deficiency is
      the most common human enzymopathy; nearly 400 different biochemical variants of
      the enzyme have been described. Sardinia is the Italian region with the highest
      frequency of this defect. METHODS: We examined genomic DNA of 16 subjects with
      G6PD Mediterranean, 2 with G6PD Athens-like, 1 with G6PD Ferrara 2 (all as
      biochemically defined). RESULTS: All G6PD Mediterranean subjects had a C-->T
      mutation at nucleotide 563 and a C-->T transition at nucleotide 1311; G6PD Athens
      like and Ferrara 2 subjects had a G-->C mutation at nucleotide 844 (the same
      mutation has been found in G6PD Seattle-like). CONCLUSIONS: This study suggests
      that in Southern Sardinia G6PD mutations are relatively homogeneous and that the
      results of biochemical characterization studies must be carefully evaluated,
      because the same mutations might be responsible for different biochemical
      behavior.

PMID- 7806086
TI  - Identification of granulocyte-macrophage colony stimulating factor receptor mRNA
      by non-isotopic in situ hybridization in bone marrow biopsies.
AB  - BACKGROUND: In the last few years many studies have been published on GM-CSF
      receptors, focusing on molecular structure, function and distribution.
      Nevertheless, protocols for detecting GM-CSF receptors on formalin-fixed paraffin
      embedded histological sections, to our knowledge, have not been described.
      METHODS: A method based on non-isotopic in situ hybridization (ISH) using a 21
      base antisense DNA oligoprobe whose 3'-end was labeled with digoxigenin 11-dUTP
      was devised. The probe was applied on 20 routinely processed bone marrow trephine
      biopsies which were considered as positive controls. RESULTS: The hybridization
      signal was seen in myeloid cells, erythroid progenitors and rare megakaryocytes.
      CONCLUSIONS: Non-isotopic ISH represents an alternative to current methodologies
      for the assessment of GM-CSF receptor expression; since it is suitable for
      routinely processed samples, it can be regarded as a helpful tool for diagnostic
      determination of GM-CSF receptors in tumors from patients receiving GM-CSF and
      for retrospective studies on archival material.

PMID- 7806087
TI  - Effects of R-enantiomer (GR66234A) and L-enantiomer (GR66235A) of telupidine, a
      new dihydropyridine derivative, on cell lines displaying the multidrug resistant
      phenotype.
AB  - BACKGROUND: Many dihydropyridine analogues with calcium channel blocker activity
      are able to reverse multidrug resistance (MDR). We studied the daunorubicin
      resistance reversing activity of the R enantiomer (GR66234A) and the L-enantiomer
      (GR66235 A) of teludipine, a new lipophilic calcium channel blocker synthesized
      by Glaxo. METHODS: The daunorubicin resistance reversing activity of the
      enantiomers of teludipine was evaluated in two MDR cell lines: ARNII, an
      erythroleukemia cell line which expresses p-glycoprotein, and MCF 7/R, a breast
      cancer cell line with p-glycoprotein and high levels of glutathione S transferase
      (GST) and glutathione peroxidase (GSH Px). RESULTS: GR66234A and GR66235A show
      the same activity in reversing daunorubicin resistance and are more effective
      than verapamil. The difference in activity between verapamil and the enantiomers
      of teludipine is greater in ARNII cells than in MCF 7/R cells. Nevertheless,
      there are no significative differences in cellular daunorubicin accumulation
      between ARNII and MCF 7/R following exposure to teludipine, nor are there
      differences in intracellular daunorubicin distribution in the presence of either
      MDR reversing agent. CONCLUSIONS: The low calcium channel antagonistic activity
      of GR66234A suggests that this compound may be useful in combination with
      chemotherapy in MDR malignancies.

PMID- 7806088
TI  - Prognostic value of bone marrow histology in chronic lymphocytic leukemia. A
      study of 335 untreated cases from a single institution.
AB  - BACKGROUND AND METHODS: A significant correlation between bone marrow (BM)
      histology, survival and disease progression (DP) probability has been observed by
      several authors in chronic lymphocytic leukemia (CLL). The prognostic value of BM
      histologic patterns on survival and disease progression probability was
      investigated in 335 B-CLL patients. RESULTS: Actuarial survival probability
      estimated by univariate analysis proved to be significantly influenced by stage
      (p < 0.0001), BM histology (p = 0.01), and by the following parameters: anemia (p
      = 0.0005), splenomegaly (p < 0.001), CLL-related symptoms (p < 0.01),
      thrombocytopenia (p < 0.01), number of involved nodal areas (p = 0.01) and
      peripheral lymphocyte count over 30 x 10(9)/L (p < 0.05). In this series we did
      not detect a discriminating prognostic effect for BM histology within the
      individual stages. Cox multivariate regression analysis failed to demonstrate a
      significant value for BM histology, while stage and anemia emerged as the best
      prognostic variables. Actuarial DP free probability in 294 untreated patients
      with A and B stages was significantly related to stage (p < 0.00001) and to BM
      pattern (p = 0.01). CONCLUSIONS: Despite the clear correlation between the D
      pattern of BM involvement and advanced and early progressive disease, we were
      unable to demonstrate an independent prognostic value for BM histology. These
      findings suggest that stage emerged as the best predictive factor of survival
      probability in our B-CLL patients.

PMID- 7806089
TI  - Evaluation of erythropoietin in endurance runners.
AB  - To evaluate the role of erythropoietin (Epo) in the erythroid abnormalities often
      found in athletes, Epo was evaluated by radioimmunoassay in endurance runners
      (ER). In a first study, 46 experienced ER, 11 with iron deficiency (ID group),
      were studied during a training period. In ID and non-ID runners, serum Epo (SEpo)
      levels were similar to sedentary controls (ID = 19.1 +/- 4.9 U/L, non-ID = 19.7
      +/- 5.5 U/L and controls 19.7 +/- 9.2 U/L). In a second study, serum and urine
      erythropoietin (UEpo) levels were evaluated in 17 ER during a 6-hour race.
      Samples were taken before the race (pre-race), immediately following (6-hour) and
      4 days after (post-race). No differences were observed in SEpo levels (pre-race =
      19.8 +/- 4.1 U/L, 6-hour = 21.2 +/- 4.9 U/L and post-race = 21 +/- 4 U/L), but
      UEpo increased following the race (pre-race = 15.4 +/- 9.6 U/L, 6-hour = 26.1 +/-
      6.2 U/L and post-race = 14.1 +/- 6.5 U/L) (p < 0.0001) and this UEpo increase was
      related to urine creatinine changes (rs = 0.79, p < 0.00001). In conclusion, SEpo
      in ER does not differ from sedentary values and does not vary with competition;
      however, UEpo increases during a long-distance race. These data may be important
      for a correct evaluation of Epo abusers and sports anemia.

PMID- 7806090
TI  - 3q aberration and monosomy 7 in ANLL presenting with high platelet count and
      diabetes insipidus.
AB  - Diabetes insipidus and thrombocytosis were presenting symptoms in a case of adult
      ANLL-M1. Cytogenetic investigations revealed a typical 3q rearrangement, i.e.
      inv(3)(q21q26). A subclone with monosomy 7 was also found and documented by FISH
      analysis. Correlations between clinical/hematological features and
      cytogenetic/FISH results are discussed.

PMID- 7806091
TI  - Essential thrombocythemia in pregnancy: report of four cases.
AB  - We report four pregnancies in four patients with essential thrombocythemia (ET).
      In two cases pregnancy resulted in spontaneous abortion at 6 and 11 weeks of
      gestation, respectively. The other two had a full-term, normal delivery; one of
      them received no therapy during the pregnancy, whereas the other was treated with
      acetylsalicylic acid from 11 weeks for signs of threatened abortion. No
      thrombotic or hemorrhagic complications were observed in any of the patients
      during pregnancy or the post-partum period. We believe that pregnancy in patients
      with ET represents a risk. Close monitoring is therefore indispensable and
      antiaggregant therapy might be of benefit.

PMID- 7806092
TI  - AL-amyloidosis in monoclonal gammopathies.
AB  - Sixty-two patients affected by MGUS underwent fat tissue aspirate examination for
      diagnosis of AL amyloidosis. Nine out of the 62 were found to be Congo red
      positive. MGUS had already been diagnosed for quite a long time in about 60% of
      these patients, while this prevalence decreased to 24% among the Congo red
      negative patients. The follow-up of the positive patients is reported.

PMID- 7806093
TI  - Development of autoimmune thyroid diseases during long-term treatment of
      hematological malignancies with alpha-interferons.
AB  - In recent years recombinant alpha-interferons (alpha-IFNs) have been widely used
      in the treatment of several hematological malignancies. Prolonged courses of IFN
      have been shown to induce autoantibodies and to support the exacerbation or even
      the development of autoimmune diseases. In this report we describe the
      development of symptomatic autoimmune thyroid diseases in 4 (7.4%) out of 54
      patients in chronic treatment with recombinant alpha-IFNs in our department. Two
      patients developed a disease resembling Hashimoto's thyroiditis after 17 and 49
      months of continuous IFN treatment, while the other two developed a typical
      Graves' disease after 41 and 52 months of therapy. The mechanism by which IFN
      induces autoimmune thyroid diseases, the choice of searching for anti-thyroid
      autoantibodies before starting long-term IFN treatment, the option of
      discontinuing IFN therapy in the presence of overt thyroid diseases, and the
      management of these diseases are discussed.

PMID- 7806094
TI  - Thrombotic thrombocytopenic purpura: a rare late complication of allogeneic bone
      marrow transplantation.
AB  - Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) usually
      occurs in a setting of systemic infection or graft-versus-host reaction during
      the first weeks following transplant. We report a case of fatal TTP that
      developed eight months after allogeneic bone marrow transplantation (BMT) without
      any evident association with other transplantation-related complications.
      Conditioning chemotherapy could have induced the disorder by causing damage to
      the vascular endothelium. The removal of immunosuppression, including cessation
      of cyclosporin A (CyA), may have precipitated the disease.

PMID- 7806095
TI  - Report on the Fifth International Workshop on Human Leukocyte Differentiation
      Antigens, Boston, November 3-7, 1993.

PMID- 7806097
TI  - Extramedullary bone marrow tumor in thalassemia.

PMID- 7806096
TI  - Hemostatic and metabolic abnormalities in diabetes mellitus. The search for a
      link.
AB  - BACKGROUND: As many as 80% of diabetic patients die from major thrombotic
      complications of atherosclerosis, stroke and myocardial infarction. Plasma and
      cellular components of the hemostatic system are often abnormal in diabetic
      patients, and some of these abnormalities may play a role in the high risk of
      thrombosis in these patients. MATERIALS AND METHODS: Clinical studies imply that
      certain hemostatic abnormalities of diabetic patients are related, to some
      extent, to poor metabolic control. Thus, a critical review of the data available
      in the specialized literature has been carried out. RESULTS: Although suggestive,
      the link between hemostatic and metabolic abnormalities in diabetes mellitus is
      only circumstantial. Little is known about similarities and differences between
      type I and type II diabetes mellitus with respect to hemostatic parameters.
      Likewise, current understanding of the effects on the hemostatic system of the
      combination of glucose and lipid abnormalities often coexisting in diabetic
      patients is rather limited. CONCLUSIONS: Ad hoc studies are mandatory to clarify
      unsolved issues in this field and define the extent to which good metabolic
      control is crucial to preventing the risk of thrombosis in diabetes mellitus.

PMID- 7806098
TI  - [Reconstruction of lower urinary tract in patients with neurogenic bladder ].
AB  - Between 1988-1993 we performed lower urinary tract reconstruction in 30 patients
      with neurogenic bladder. The indications for surgery included urinary
      incontinence and/or upper urinary tract deterioration. 18 patients with a follow
      up of longer than 18 months are reported. Continence was achieved in 15 of 16
      patients and stabilization or improvement of the upper tracts in 17 of 18
      patients. There was no mortality, and morbidity was the same as in similar
      series. Despite its complexity, lower urinary tract reconstruction in patients
      with neurogenic bladder brings major improvement in quality of life and in
      preservation of renal function. We recommend such operations in properly selected
      patients.

PMID- 7806099
TI  - [Laparoscopic and thoracoscopic surgery in children and adolescents].
AB  - Initial experience with laparoscopic and thoracoscopic surgery in children during
      the year Sept. 1992-Sept. 1993 is presented. The 36 procedures included 20
      appendectomies, 3 cholecystectomies, 10 upper thoracic sympathectomies, 1
      bilateral oophorectomy and 2 diagnostic laparoscopies. Indications were
      appendicitis, symptomatic gallstones, idiopathic primary palmar hyperhidrosis,
      and gonadal dysgenesis (xo/xy mosaicism) in a 13-year-old girl. 2 diagnostic
      laparoscopies were performed for chronic abdominal pain and for a possible
      retroperitoneal lesion, respectively. All procedures were successfully managed
      without complications. In 2 cases of acute appendicitis it was necessary to
      change to the open conventional technique because of technical difficulties.
      Duration of hospitalization for cholecystectomy and sympathectomy was
      significantly shorter than with the conventional surgical approach and
      convalescence was excellent, with less postoperative pain. As for the surgical
      approach in acute appendicitis, we cannot as yet decide whether or not
      laparoscopy is superior to the conventional technique.

PMID- 7806100
TI  - [Tuberculous lymphadenitis in a general hospital].
AB  - All cases of tuberculous lymphadenitis admitted over a 43-year period (1951-1993)
      were surveyed. The diagnosis was validated in 188 cases. The incidence was 2.74
      cases per year, but there was a cluster of 94 cases in the first 20 years. 50.8%
      had local signs alone, while 36.4% had both local and systemic signs. Nodes
      affected showed either painless or painful swelling, and sometimes there was
      drainage. Cervical nodes were affected most frequently, and the commonest general
      symptom was fever, followed by fatigue. In 28.8% there was pulmonary
      tuberculosis, in 14.4% other forms of extrapulmonary tuberculosis, and in 9.3%
      only active tuberculous lymphadenitis. Most of the patients had immigrated to
      Israel from eastern Europe and the Yemen. Though tuberculous lymphadenitis has
      become infrequent, it is still the commonest form of extrapulmonary tuberculosis.
      A high index of suspicion is needed to diagnose accurately and treat this
      potentially curable condition.

PMID- 7806101
TI  - [Chronic diseases in immigrants from Russia (CIS) at a primary care clinic and
      their sociodemographic characteristics].
AB  - 397 new immigrants to Israel ("olim") were under medical treatment at a primary
      care clinic during the first year (1990-1991) after their immigration to Israel
      ("aliyah") from 14 republics of the Commonwealth of Independent States (CIS,
      formerly the Soviet Union). Most of the olim were between 1-19 years of age. More
      than three-quarters were married and about a third of the women were widowed or
      divorced. The other patients were bachelors, separated men or women, or divorced
      men. More than a third had 16 years or more of education. More than a third of
      the families consisted of 2 members, while more than three-quarters had both
      parents, and about a quarter only 1 parent, usually the mother. Half the families
      had children; more than a quarter of the adults had not been employed in the CIS,
      while in Israel 58.8% were. 464 diagnoses of chronic diseases had been made in
      the CIS, (1.2/person), of which 75% were verified in Israel. 185 cases
      (0.5/person) not previously reported were diagnosed or had developed in Israel.
      The most frequent were cardiovascular, and next digestive tract disease, followed
      by endocrine, metabolic and musculoskeletal-connective tissue diseases. The
      overall prevalence rate of ischemic heart disease among men aged 20 < or = 65
      years was 18.8%, compared to 5.8% among veteran Israelis. Among women the rates
      were 9.5% and 4.0%, respectively. The prevalence of hypertension (> or = 160/95)
      was 14% among men and 21% among women; in veteran Israelis it was 14% for both
      men and women. The prevalence of diabetes among men was 4.1%, and 5.4% among
      veteran Israelis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7806102
TI  - [Coomb's-positive hemolytic anemia and tuberculosis in Kaposi's sarcoma treated
      with interferon].
AB  - Immune hemolytic anemia and reactivated tuberculosis developed in a patient
      treated with alpha-interferon for Kaposi's sarcoma and splenic non-Hodgkin's
      lymphoma. The hemolytic process stopped on cessation of interferon and initiation
      of corticosteroid therapy, and the Coomb's test became negative. The possibility
      of reactivation of tuberculosis by interferon is discussed.

PMID- 7806103
TI  - [Thromboembolic events in heparin-induced thrombocytopenia].
AB  - Thrombocytopenia following heparin treatment appears in 5% of patients so
      treated. In 20% of such patients paradoxical thromboembolic phenomena may be
      associated with the thrombocytopenia. This process is most probably mediated via
      an antibody reaction against a heparin-platelet complex. We present a 70-year-old
      woman with recurrent episodes of lower extremity thrombophlebitis associated with
      thrombocytopenia following treatment with heparin for pulmonary embolism.

PMID- 7806104
TI  - [Implication of compensation in recovery from combat-induced post-traumatic
      stress disorder].
AB  - The effect of compensation payment on long-term adjustment of soldiers with war
      induced psychic trauma was studied. 2 groups of combat stress reaction casualties
      of the 1982 Lebanon War were examined: 109 casualties had been recognized by the
      Ministry of Defence as eligible for benefits, while 111 casualties had not
      applied for compensation benefits. Data were collected from their IDF medical
      charts and computerized personal records, from clinical data collected by IDF
      clinicians, and by mail and telephone surveys. Results indicated that the groups
      were quite similar in social functioning before the war. However, in those
      compensated there was more distress and impaired functioning following the war
      and at follow-up. The role of compensation in recovery from war-induced psychic
      trauma is discussed.

PMID- 7806105
TI  - [Effect of corticosteroids on inspiratory muscle function].
AB  - Functional alteration in inspiratory muscles was evaluated in patients receiving
      corticosteroids for nonrespiratory diseases. Inspiratory muscle strength, as
      expressed by maximal inspiratory mouth pressure (PImax), and inspiratory muscle
      endurance (PmPeak/PImax), determined with a pressure threshold breathing device,
      were evaluated in 8 patients with normal pulmonary and inspiratory muscle
      function. There was a gradual decrease in both inspiratory muscle strength and
      endurance when corticosteroids were given. Tapered decrease in steroid dosage
      resulted in marked improvement in both strength and endurance, and the
      improvement was even more significant 6 months later. We also evaluated the
      ability of specific inspiratory muscle training to prevent the effects of
      therapeutic corticosteroids on inspiratory muscle function in 6 patients, as
      compared to 6 control patients who received sham training. Following
      corticosteroids there was a gradual decrease in both inspiratory muscle strength
      and endurance in those getting sham training. However, there was no significant
      change in inspiratory muscle function in those getting inspiratory muscle
      training. We conclude that corticosteroids result in significant deterioration in
      respiratory muscle function. This weakness is reversible by tapering steroid
      dosage, but can be prevented by specific inspiratory muscle training during
      corticosteroid treatment.

PMID- 7806106
TI  - [Bladder reconstruction by augmentation enterocystoplasty].

PMID- 7806107
TI  - [Routine ultrasound examination during pregnancy--is it really necessary?].

PMID- 7806108
TI  - [Chronic fatigue syndrome].

PMID- 7806109
TI  - [Intra-uterine growth retardation--many questions, but still limited treatment
      modalities].

PMID- 7806110
TI  - [Mechanisms of interstitial fibrosis in chronic renal failure].

PMID- 7806111
TI  - [Biofeedback for fecal incontinence and constipation].

PMID- 7806112
TI  - [Asymptomatic bacteriuria in the elderly].

PMID- 7806114
TI  - [Epidemiological aspects of alcohol hazards].

PMID- 7806113
TI  - [Obidoxime (Toxogonin): a critical review].

PMID- 7806115
TI  - [Genetics and regulation of anti-DNA antibody idiotypes in lupus].

PMID- 7806116
TI  - [Neuron-specific enolase as a tumor marker].

PMID- 7806117
TI  - [Current status of basic antirheumatic therapy].
AB  - Basic treatment of inflammatory rheumatic diseases is effective, but not
      necessarily remission-inducing. Its mechanisms of action are only partly
      understood, and the reasons for the variations in response rate of between 40 and
      80% are also unknown. The original concept of starting with the least toxic of
      these substances, and then only after the failure of treatment with non-steroidal
      anti-inflammatory drugs, has now been abandoned. Taking compliance as a measure
      of therapeutic value, among the most important of the substances employed,
      methotrexate is the most, oral gold the least, favorable, while azathioprine,
      sulfasalazine, antimalarial agents and D-penicillamine do not differ
      significantly from another.

PMID- 7806119
TI  - [Premature interpretation of prescription data can be erroneous.
      Pharmacoepidemiology--chance and risk].

PMID- 7806118
TI  - [Clinical relevance of the antiphospholipid syndrome. Antiphospholipid antibodies
      in a mixed rheumatologic patient sample].
AB  - The antiphospholipid syndrome may occur either in association with systemic lupus
      erythematosus (SLE) or as a primary condition. Diagnostic criteria include the
      detection of antiphospholipid antibodies using cardiolipin antigen
      (anticardiolipin antibodies, ACA) or lupus anticoagulant, and at least two
      clinical manifestations, primarily venous or arterial thrombosis,
      thrombocytopenia or repeated miscarriage. Among 200 patients with various
      rheumatic diseases, a pathological ACA test in excess of 44 U/ml was detected
      with ELISA in 81 cases (41%), and of these 30% had values exceeding 100 U/ml.
      Both overall positive reactions and the particularly high titers were clearly
      more common among patients with rheumatoid arthritis (RA) and collagen disease,
      namely 51% and 33%, respectively, than in patients with sero-negative
      spondylarthritis and non-inflammatory diseases of the locomotory system (22%
      pathological, 13% highly pathological, titers. Correlations were also found with
      miscarriage in women, positive rheumatoid and antinuclear factors, and the number
      of diagnostic criteria of RA or SLE presenting. A questionnaire survey -
      evaluating 84 subjects, half with positive and half with negative, ACA reactions 
      confirmed the correlation between miscarriage and the detection of ACA.

PMID- 7806120
TI  - [Diagnosis and therapy of tumor pain. 1: Classification of tumor pain].

PMID- 7806121
TI  - [AIDS: combination drug partner for AZT. HIV infection--new nucleoside analog].

PMID- 7806122
TI  - [Intestine-associated immune system stimulation. Saccharomyces boulardii-
      mechanism of action].

PMID- 7806123
TI  - [A long, common path for patient and therapist. Psychotherapy. 1. Psychoanalytic
      therapy].

PMID- 7806124
TI  - [Neural therapy in the light of recent data].
AB  - In German-speaking countries, local injection of anesthetic is a popular form of
      treatment, either as "neural therapy", a complementary method intended to
      stimulate adaptive body functions, or as pure analgesia. While the latter is
      unquestionably effective, neither the rationale nor the individual mechanisms,
      nor its therapeutic efficacy have been investigated scientifically. Recent data
      show that the analgesic effect does not depend on the injection of local
      anesthetic. It is conceivable that this form of treatment acts via a mechanism
      known as diffuse noxious inhibition control.

PMID- 7806125
TI  - [Focal splenic lesion--ultrasound diagnosis. Follow-up studies--duplex
      examination--interventional ultrasound].

PMID- 7806126
TI  - [Diagnosis and therapy of tumor pain. 2: Drug treatment--"peripherally" active
      analgesics].

PMID- 7806127
TI  - [Therapy of ischemic heart disease with Trapidil. Observations with 4,014
      patients in medical practice].
AB  - METHOD: Within the framework of a user observations study, 4,014 patients with
      ischemic heart disease were treated with Trapidil and kept under observation for
      12 weeks. RESULTS: During the course of therapy, a decrease in the incidence and
      intensity of attacks of angina pectoris and in the number of weekly short-term
      nitrate applications was observed. Side effects, most commonly nausea, headache,
      GI complaints and giddiness, were reported by only 3.8% of the patients. The
      efficacy of the preparation was assessed to be good or very good in more than
      89%, tolerability in more than 90%, of the cases. These results are in accord
      with the assessment in reports in the international literature to the effect that
      Trapidil has a good therapeutic action.

PMID- 7806128
TI  - New pathway to CNEP.

PMID- 7806130
TI  - Vanadate has no effect on insulin-extraction by the rat liver.
AB  - The mechanism(s) responsible for the insulin-like effects of vanadate are still
      unclear, although several possible explanations have been raised. However, the
      possibility that vanadate induces inhibition of insulin degradation in the liver
      was not examined yet. Therefore, in the present study we examined the effect of
      vanadate on the extraction of insulin by the perfused rat liver using an open,
      non-recycling system. Baseline insulin extraction (44 +/- 2% and 37 +/- 3%) was
      not affected by the administration of 1 and 5 microM vanadate (decreased to 42 +/
      2% and 36 +/- 1, respectively, p = NS). Vanadate had no adverse effects on liver
      viability, and the bile flow remained stable during and after vanadate
      administration (0.87 +/- 0.08 microliter/min/g liver prior to Vs. 0.084 +/- 0.11
      microliter/min/g liver following vanadate administration). This study shows that
      vanadate does not inhibit insulin extraction by the perfused liver, and that does
      of vanadate that effectively inhibit hepatic glucose production possess no
      adverse effects on liver viability.

PMID- 7806129
TI  - Effect of the number of islets on the outcome after transplantation in
      streptozotocin-induced diabetic rats.
AB  - This study tested the hypothesis that normalization of glucose homeostasis after
      islet transplantation is correlated to the number of islets, and by increasing
      this number a complete normalization of glucose homeostasis could be achieved,
      1,200 or 2,400 islets were transplanted into the left kidney subcapsular space in
      streptozotocin-induced diabetic rats. Intravenous glucose tolerance tests were
      performed at 10 days, 3 and 6 months after transplantation. Transplantation of
      both 1,200 and 2,400 islets normalized the basal blood glucose levels within 24
      48 hours, which remained normal for the entire study period of 6 months. Basal
      plasma insulin levels and body weight were also normalized in both transplanted
      groups. Transplantation of 2,400 islets achieved normal glucose-induced insulin
      secretion at 10 days after transplantation and for the following 6 months. In
      contrast, glucose intolerance was present in rats transplanted with only 1,200
      islets. It is concluded that complete glucose homeostasis after islet
      transplantation is dependent on the number of transplanted islets and can be
      achieved by increasing this number.

PMID- 7806131
TI  - Temporal effects of prolactin on casein kinase activity, casein synthesis and
      casein mRNA accumulation in mouse mammary gland explants.
AB  - Studies were carried out to investigate the mechanism by which prolactin
      stimulates casein synthesis in cultured mouse mammary tissues. The onset of the
      prolactin stimulation of casein synthesis occurs 8-10 hours after prolactin
      addition to cultured tissues; a maximum effect is evoked by 16 hours. A similar
      time-course of response to prolactin was observed when the tissue accumulation of
      the mRNA for beta-casein was determined. At 16 hours, however, prolactin had no
      effect on tissue-specific casein kinase activity which is associated with the
      Golgi apparatus. These studies suggest that the tissue content of casein mRNA is
      causally related to the onset of the prolactin stimulation of casein synthesis in
      cultured mouse tissues. In contrast, the activity of the kinase that catalyzes
      the phosphorylation of the caseins is not altered by prolactin and thus
      apparently is not a contributing factor to the early prolactin effect on casein
      synthesis.

PMID- 7806132
TI  - Effect of treatment with contraceptive steroids on the sexual behaviour of rats
      pretreated with benzpyrene or allylestrenol in fetal or neonatal age.
AB  - Treatments with contraceptive steroids significantly reduced the receptivity of
      adult female rats. This effect was not observed in ovariectomized females treated
      with high doses of estrogen and gestagen hormones prior to the investigation. The
      receptivity was also significantly reduced in rats treated with steroids
      (allylestrenol or benzpyrene) in their fetal or neonatal age, as it was
      demonstrated in previous experiments. The contraceptive treatment of the above
      described, pretreated adults resulted in improved function of receptivity, but it
      had no difference compared to the group which was only treated with
      anticoncipient. This means that neonatal treatment with allylestrenol or
      benzpyrene does not influence the effects of contraceptive steroids on the sexual
      behaviour (receptivity). The two effects are not additive.

PMID- 7806133
TI  - Effect of retinoic acid on prostaglandin F2 alpha-induced prostaglandin E2
      synthesis in osteoblast-like cells.
AB  - We previously reported that prostaglandin F2 alpha (PGF2 alpha) stimulates
      phosphoinositide hydrolysis via pertussis toxin-sensitive GTP-binding protein in
      osteoblast-like MC3T3-E1 cells (Miwa, Tokuda, Tsushita, Kotoyori, Takahashi,
      Ozaki, Kozawa and Oiso 1990) and that PGF2 alpha stimulates arachidonic acid
      release and prostaglandin E2 (PGE2) synthesis, and the activation of protein
      kinase C (PKC) amplifies the effect of PGF2 alpha in MC3T3-E1 cells (Tokuda, Oiso
      and Kozawa 1992). In the present study, we investigated the effect of retinoic
      acid (RA), a vitamin A (retinol) metabolite, on PGF2 alpha-induced PGE2 synthesis
      in MC3T3-E1 cells. The pretreatment with RA, which by itself had little effect on
      synthesis, significantly inhibited PGE2 synthesis induced by PGF2 alpha in a dose
      dependent manner in the range between 1 nM and 0.1 microM. This effect of RA was
      dependent on the time of pretreatment up to 8 h. In addition, RA inhibited the
      amplification of PGF2 alpha-induced PGE2 synthesis by 12-O-tetradecanoylphorbol
      13-acetate, known to be a PKC activator. However, RA had little effect on PGE2
      synthesis induced by melittin, known as a phospholipase A2 activator. Moreover,
      pertussis toxin had little effect on arachidonic acid release induced by PGF2
      alpha. These results strongly suggest that RA inhibits PGE2 synthesis induced by
      PGF2 alpha in osteoblast-like cells and the inhibitory effect is exerted at the
      point prior to the activation of phospholipase A2.

PMID- 7806134
TI  - Lipoprotein(a) serum levels in post-menopausal women treated with oral estrogens
      administered at different times.
AB  - The different effects on serum lipoprotein(a) [Lp(a)] levels by administering
      estrogens at different times of the day (8 a.m. and 8 p.m.) were evaluated in
      twenty-four post-menopausal women. Patients were assigned to one of the two
      treatment groups by random sampling numbers. Patients of both groups received
      0.625 mg conjugated equine estrogens daily per os for 21 days. Group A patients
      (n: 9) received the pill at 8 a.m., and group B patients (n: 12) received the
      pill at 8 p.m. There were no statistically significant differences between the
      two treatment groups as regards the anthropometric characteristics, the basal
      values of the Lp(a), the sex steroid and pituitary hormone levels. Administration
      of conjugated equine estrogens resulted in decreased levels of Lp(a) only in
      group B after treatment. The different Lp(a) behaviour in the two groups and in
      the presence of the same serum hormonal levels, seems to be dependent on the
      existence of a circadian rhythm of the hepatic responsiveness to estrogens, whose
      expression is higher during evening hours.

PMID- 7806135
TI  - Increase in calciuria and oxaluria after a single chocolate bar load.
AB  - Chocolate, a foodstuff rich in sucrose, fat and oxalate, is considered unsuitable
      in cases of obesity, diabetes mellitus, urolithiasis and postprandial
      hypoglycemia. However the pathophysiological effects of chocolate are poorly
      documented. Therefore we investigated the effects of ingestion of 100 g dark
      chocolate bar (45 g cocoa and 55 g sucrose) on carbohydrate, calcium and oxalate
      metabolisms in 10 healthy subjects. Results were compared to those of 55 g
      sucrose intake (control group) performed on another day. Chocolate caused i) a
      lesser but longer increase in plasma glucose, insulin, and C-peptide than sucrose
      (respectively +23% of baseline vs +60%, p < 0.001; +436% of baseline vs +755%, p
      < 0.01 and +200% of baseline vs +331%, p < 0.01), ii) a striking increase in
      triglyceridemia, calciuria and oxaluria (respectively +96%, p < 0.01; +147%, p <
      0.01 and +213%, p < 0.001). Thus, chocolate (cocoa+sucrose) causes a lesser
      pancreatic stimulation than sucrose. However, the increases in both calciuria and
      oxaluria (induced respectively by sucrose and cocoa) following chocolate
      ingestion might contribute to urinary conditions favoring the development of
      calcium oxalate calculi.

PMID- 7806136
TI  - Pancreas lipoxygenase arachidonic acid metabolites production in streptozotocin
      induced diabetes in rats.

PMID- 7806137
TI  - Oxypurine metabolism of xanthine oxidase-deficient hepatoma-derived cell line HuH
      7. Effect of exogenous purines and allopurinol.

PMID- 7806138
TI  - Insulin response to intravenous glucose injection in a family with a glucokinase
      mutation.

PMID- 7806139
TI  - Effect of prednisone on thyroid function in children with nephrotic syndrome.

PMID- 7806140
TI  - Analysis of the precore DNA sequence and detection of precore antigen in liver
      specimens from patients with anti-hepatitis B e-positive chronic hepatitis.
AB  - A number of naturally occurring hepatitis B virus (HBV) mutants unable to
      synthesize the hepatitis B e antigen (HBeAg) have been identified in patients
      characterized by HBV DNA and anti-HBe in their serum. Because the analysis of the
      HBV-associated DNA and antigens in the liver tissue is still not complete, we
      investigated the precore sequence of HBV DNA and its encoded proteins in the
      liver tissue of 32 patients positive for HBV DNA and anti-HBe in their serum.
      Three different groups of patients were identified. Group I (n = 14) was
      characterized by viral DNA sequences with a G-A transition in the distal precore
      gene region, thus creating a termination codon (TAG). Liver tissue from this
      group was negative for HBeAg but positive for hepatitis B core antigen (HBcAg)
      and a peptide containing the last 10 aminoacids of the precore and the first four
      aminoacids of the c region. Group II (n = 6) showed variable mutations in base
      sequences further upstream and negative for HBeAg and the precore peptide. Group
      III (n = 12) contained wild-type HBV DNA sequences in the tissue and positivity
      for precore- and core-encoded proteins. We conclude from our study that the group
      of patients with HBV DNA and anti-HBe in the serum is rather heterogeneous,
      including HBV DNA mutations in the precore region as well as infection with the
      wild-type virus being negative for HBeAg in the serum. The precore peptide is
      produced and expressed in the tissue even when the formation of a stop codon at
      base 1896 prevents the complete translation of the entire HBe protein.

PMID- 7806141
TI  - Predicting survival in fulminant hepatic failure using serum Gc protein
      concentrations.
AB  - Plasma Ge protein sequesters actin released into the circulation after massive
      hepatocyte necrosis, but is greatly depleted in the process. In fulminant hepatic
      failure (FHF), Gc is present in serum both as a complex with actin and as unbound
      protein, the latter becoming completely exhausted in those patients with the most
      severe FHF. In the present study, 47 consecutive patients with FHF, 39 of whom
      were the result of acetaminophen (AC) overdose, were evaluated to determine
      whether measurement of Gc protein levels could be used to predict survival. Using
      serum samples obtained shortly after admission as well as later samples, levels
      for total Gc protein, percentage of Gc complexed with actin, and calculated
      unbound Gc remaining in serum were compared for survivors and those who died of
      their illness. The most marked changes were present in unbound Gc levels in
      nonsurvivors, the mean of which for follow-up samples was 10% of normal mean
      values, as compared with 23% of normal mean values in those who survived (P <
      .01). Using a cutoff value for unbound Gc protein of > or = 34 micrograms/mL to
      predict survival, outcome was correctly predicted in 32 of 47 (68%) patients
      using early samples, and in 24 of 27 (89%) patients using later sera. No
      differences were observed between values and/or outcome in AC and non-AC cases.
      Measurement of Gc protein level correctly predicted all patients dying of hepatic
      failure. This single measurement compares favorably with multifactorial
      predictive models, such as the King's College model, and might be a useful test
      for patients being considered for transplantation.

PMID- 7806142
TI  - Serum hepatocyte growth factor levels in liver diseases: clinical implications.
AB  - Although recent studies have shown that hepatocyte growth factor (HGF) is a
      potent mitogen in vivo, the significance of serum HGF in liver diseases remains
      unclear. To clarify clinical significance of serum HGF in liver diseases, serum
      HGF was measured in 127 patients with liver diseases and in 200 healthy
      individuals, using a highly sensitive immunoradiometric assay (IRMA). This assay
      is specific for HGF and is sensitive enough to detect 0.1 ng/mL of HGF. Mean
      values for serum HGF in acute hepatitis (AH), chronic hepatitis (CH), liver
      cirrhosis (LC), hepatocellular carcinoma (HCC), primary biliary cirrhosis (PBC),
      fulminant hepatic failure (FHF), and normal controls were 0.45, 0.40, 1.05, 1.06,
      0.44, 16.40, and 0.27 ng/mL, respectively. Serum HGF levels in these diseases
      were significantly increased compared with those in the controls (P < .001), and
      exhibited a positive correlation with total bilirubin, indocyanine green (ICG)
      test (R15), asparate aminotransferase (AST), and a negative correlation with
      albumin and prothrombin time (P < .001). Cirrhotic patients with modified Child
      class C had higher levels of serum HGF than those graded as modified Child class
      A or B (P < .001). In CH, serum HGF levels were significantly related to the
      histological activity index (HAI) score (P < .002). Seven patients with HCC who
      underwent transcatheter arterial embolization (TAE) exhibited a gradual increase
      in serum HGF levels up to day 4 after treatment; these higher levels were
      maintained until day 7, although AST reached a peak on day 2 and then decreased
      gradually.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7806143
TI  - Cytokine patterns and cytotoxic mediators in primary biliary cirrhosis.
AB  - Primary biliary cirrhosis (PBC) is an autoimmune disease of the liver with
      unknown etiology. Autoreactive T lymphocytes that infiltrate the liver may play a
      major role in the bile duct damage that accompanies the disease. We hypothesized
      that cytokines produced by T lymphocytes and other cells are central to the
      disease process. Therefore, we used reverse transcription-polymerase chain
      reaction (PCR) and Southern hybridization to identify cytokine message directly
      from liver tissue of 11 patients with PBC and 5 patients with autoimmune
      hepatitis (AI-CAH). Messenger RNA (mRNA) for interleukin (IL)-2, IL-5, IL-6,
      interferon gamma (IFN-gamma), and transforming growth factor beta (TGF-beta) were
      detected in the majority of the specimens from patients with PBC. The presence of
      IL-5 was associated with PBC (P < .001, PBC vs. AI-CAH). Because IL-5 is a potent
      eosinophil differentiation factor, we looked for evidence of activated
      eosinophils within the infiltrate. We observed the deposition of the primary
      cytotoxic granule protein of eosinophils, major basic protein (MBP), within the
      portal region of livers from patients with PBC. Moreover, we detected message for
      a cytotoxic T-lymphocyte (CTL) granzyme in 87.5% of these livers indicating that
      mature CTL are present. Thus, we present evidence for two effector pathways that
      may contribute to the tissue damage observed in PBC and have identified message
      for cytokines that may regulate these pathways.

PMID- 7806144
TI  - Differential alterations of cytochrome P450 proteins in livers from patients with
      severe chronic liver disease.
AB  - To determine whether cytochrome P450 proteins were differentially altered in
      severe chronic liver diseases, we examined 50 livers removed at liver
      transplantation from patients with end-stage cirrhosis, including 18 with and 32
      without cholestasis, and compared the results with 21 histologically normal
      livers. NADPH-cytochrome c reductase activities were unaltered in microsomes from
      cirrhotic livers. Total cytochrome P450 content was significantly reduced. The
      catalytic activities of four xenobiotic-metabolizing P450s and the level of the
      corresponding proteins were differentially altered. Thus, P450 3A-supported
      testosterone 6 beta-hydroxylase activity and 3A protein appeared to be reduced,
      but only in the subgroup without cholestasis was this change significant. In
      contrast, 2E1 and the related N,N-dimethylnitrosamine N-demethylase activity were
      clearly reduced in livers from patients with cholestatic forms of cirrhosis but
      appeared not to be changed in other cirrhotic livers. Similarly, P450 2C protein
      was reduced only in patients with severe chronic cholestasis. Finally, P450 1A2
      and 1A2-supported ethoxyresorufin O-deethylase activity were significantly
      reduced in hepatic microsomes from patients with both types of advanced liver
      disease. In summary, these data demonstrate that cytochrome P450 proteins are
      selectively altered in severe chronic liver disease, some being profoundly
      decreased, others less so or not at all. Our results also suggest that there may
      be different patterns of altered hepatic P450 expression according to the
      presence or absence of cholestasis in patients with cirrhosis severe enough to
      require transplantation.

PMID- 7806145
TI  - Pediatric liver transplantation for Langerhans' cell histiocytosis.
AB  - Langerhans' cell histiocytosis (LCH) represents 15% to 20% of sclerosing
      cholangitis (SC) in children. In LCH-associated SC, a very poor response to
      chemotherapy has been reported, and spontaneous prognosis is very bad. Few cases
      of orthotopic liver transplantation (OLT) for LCH have been reported and little
      is known about the risk of recurrence and the effect of immunosuppression after
      OLT. Since 1986, five children (mean age +/- SD, 12.6 +/- 3.6 years) underwent
      OLT for SC complicating LCH. All patients presented with growth retardation, and
      severe liver disease including repeated episodes of variceal bleeding (n = 5),
      liver insufficiency (n = 4), jaundice (n = 5), and ascitis (n = 4). Four patients
      presented with previous abdominal surgery (mesocaval shunt in two and explorative
      laparotomy in two). OLT was performed using a whole (n = 2) or a reduced liver
      graft (n = 3). Pathological examination of the recipient liver showed biliary
      cirrhosis in all cases. Three patients are alive and well 9 to 88 months after
      OLT. None presented with recurrence of LCH or SC within the liver graft or in
      other organs. General condition (including growth and puberty) improved
      dramatically in the three surviving patients. Absence of recurrence after up to 7
      years of follow-up after liver transplantation in our patients, as well as in all
      other reported cases, is encouraging and shows that OLT may be indicated in end
      stage liver disease complicating LCH. Furthermore, cyclosporine may be beneficial
      for preventing recurrence of LCH, in which autoimmunologic mechanisms have been
      advocated.

PMID- 7806146
TI  - Octreotide blunts postprandial splanchnic hyperemia in cirrhotic patients: a
      double-blind randomized echo-Doppler study.
AB  - The effect of octreotide, a long-acting synthetic analog of somatostatin, on
      fasting and postprandial splanchnic hemodynamics was investigated in cirrhotic
      patients. Splanchnic hemodynamics were assessed using an echo-Doppler duplex
      system in a prospective, double-blind, placebo-controlled, crossover study
      performed on 2 separate days, 1 week apart, in 30 cirrhotic patients.
      Measurements of portal vein (PV) cross-sectional area (PV-A) and mean velocity
      (PV-V), and of superior mesenteric artery (SMA) mean velocity (SMA-V) and
      pulsatility index (SMA-PI) (an index of vascular resistance) were performed at
      baseline, 30 minutes after octreotide (200 micrograms subcutaneously) or placebo
      administration, and 30 and 60 minutes after the ingestion of a liquid meal. In
      the fasted state, octreotide induced a significant decrease in PV-V (-7%) and in
      SMA-V (-10%) and an increase in PI (+16%). On the day of placebo administration,
      meal ingestion induced a significant increase in PV-V (+21%) and in SMA-V (+43%)
      and a decrease in PI (-21%). In contrast, meal ingestion on octreotide day
      induced significantly smaller increases in PV-V (+10%) and in SMA-V (+18%) and a
      significantly smaller decrease in PI (-10%). Octreotide, although producing a
      mild reduction in PV-V and SMA-V in the fasted state, markedly blunts
      postprandial splanchnic hyperemia in cirrhotic patients.

PMID- 7806147
TI  - Hepatitis B virus precore mutant infection is associated with severe recurrent
      disease after liver transplantation.
AB  - The factors that predispose patients undergoing liver transplantation for
      hepatitis B virus (HBV) disease to severe recurrence of infection are unclear. In
      this study we examined the effect of pretransplantation infection with HBV and
      precore variant strains of HBV on posttransplantation outcome and allograft
      histology in 24 patients who survived more than 3 months after liver
      transplantation. Based on pretransplantation serum HBV DNA status as detected by
      the polymerase chain reaction (PCR) and direct sequencing, the 24 patients could
      be assigned to three groups. In group 1 there were 4 patients HBV DNA-negative
      before transplantation and none of these patients suffered recurrence of
      infection posttransplantation. In group 2, of 10 patients with pretransplantation
      infection with wild-type virus, 7 became reinfected, and 1 of these developed HBV
      related graft failure. In group 3, 9 of 10 patients infected with precore mutant
      HBV strains became reinfected. However, in contrast to the patients in group 2, 7
      patients in group 3 developed HBV-related graft loss, and 5 of these patients had
      fibrosing cholestatic hepatitis (FCH). These results indicate that infection with
      precore mutant strains of HBV predisposes a patient to early graft loss following
      transplantation.

PMID- 7806148
TI  - Employment after liver transplantation.
AB  - The objective of this study was to study the factors affecting employment after
      liver transplantation. The employment status and health status of 203 adult liver
      transplant recipients was assessed retrospectively in a survey comprising an
      employment questionnaire, the Sickness Impact Profile (SID), and the Medical
      Outcomes Survey (MOS). The patient population consisted of all surviving adult
      patients who had undergone liver transplantation between 1982 and 1992 at our
      institution and who had survived a minimum of 9 months. Fifty-seven percent of
      the recipients were employed and 43% of the recipients were unemployed. Eighteen
      percent of the recipients considered themselves not well enough to work. Other
      reasons cited for not working in the unemployed patients were early retirement
      (8%), return to school (3%), family reasons (3%), no work available (3%), and
      chose not to work (3%). Patient age, duration of disability before
      transplantation, and type of job before transplantation significantly affected
      posttransplantation employment status. Health status measurements predicting
      employment were ambulation, home management, physical functioning, and pain.
      Older recipients and those who were continuously out of the workforce for several
      years before transplantation were the least likely to return to gainful
      employment after liver transplantation. These findings have implications for
      assessing the success of liver transplantation and the implementation of
      strategies to fully rehabilitate patients after liver grafting.

PMID- 7806150
TI  - Hepatic collagen synthesis and degradation during liver regeneration after
      partial hepatectomy.
AB  - To elucidate hepatic collagen metabolism during liver regeneration after partial
      hepatectomy, we measured collagen content, collagen synthesis, and collagen
      degrading enzyme activity in the remnant livers of rats 3, 5, 7, and 14 days
      after a partial hepatectomy of 68%. Hepatic collagen synthesis was significantly
      higher 3, 5, and 7 days after partial hepatectomy than it was in sham-operated
      control rats, but there was no such difference 14 days after surgery, the maximal
      hepatic collagen synthesis being observed 5 days after surgery. Although the
      collagen concentration in the remnant liver was similar to that in the control
      liver, the total collagen content of the remnant liver increased rapidly with
      liver regeneration until 7 days after partial hepatectomy. Hepatic collagenase
      activity was similar to the control; however, hepatic cathepsin B and cathepsin L
      activity and the intracellular degradation of newly synthesized collagen were
      markedly decreased 3, 5, and 7 days after partial hepatectomy compared with the
      controls. Hepatic collagen synthesis was significantly and inversely correlated
      with cathepsin L activity and with the intracellular degradation of newly
      synthesized collagen. These findings suggest that a combination of increased
      collagen synthesis and decreased intracellular collagen degradation contributes
      to the rapid supply of collagen that is observed during the early phase of liver
      regeneration.

PMID- 7806149
TI  - The role of sodium in the uptake of ursodeoxycholic acid in isolated hamster
      hepatocytes.
AB  - The uptake of ursodeoxycholic acid (UDCA) was studied in isolated hamster
      hepatocytes. The uptake was rapid and linear up to 60 seconds for each
      concentration studied. When the uptake rate was plotted against UDCA
      concentration, the curve was nonlinear, indicating both saturable and
      nonsaturable uptake mechanisms. The nonsaturable process had a diffusion constant
      of 0.01 nmol.s-1.g of cell.mumol/L-1. The saturable component was characterized
      by a maximum rate of uptake (Vmax) of 5.68 nmol.s-1.g of cell-1 and a Michaelis
      constant (Km) of 224 mumol/L. In the presence of monensin, ouabain, and
      amiloride, the uptake of UDCA was significantly decreased by 35% to 55%, whereas
      the sodium-independent uptake of UDCA was not affected by either monensin or
      amiloride, thereby confirming sodium dependence of UDCA uptake. The sodium
      dependent uptake of UDCA was characterized by a Vmax and a Km of 1.57 nmol.s-1.g
      of cell-1 and 46 mumol/L, respectively. The rate of uptake of UDCA was maximal at
      extracellular sodium concentrations > or = 20 mmol/L. Furthermore, the uptake of
      UDCA was competitively inhibited by both taurocholic acid and cholic acid with an
      inhibitory constant (Ki) of 60 mumol/L and 48 mumol/L, respectively. Finally, 1
      mmol/L of 4,4'-diisothiocyano-2,2'-disulfonic stilbene (DIDS) inhibited solely
      the sodium-dependent uptake of cholic acid and UDCA. These findings confirm that
      the hepatocellular uptake of UDCA involves, at least in part, a sodium-dependent,
      ouabain, amiloride, and DIDS-sensitive transporter.

PMID- 7806151
TI  - Hemodynamic characteristics of the intrahepatic portal vascular bed over an
      extended flow range: a study in the isolated perfused rat liver.
AB  - The relationship between the perfusion pressure (P) and resistance (R) of the
      intrahepatic portal vascular bed was determined in isolated rat liver
      preparations perfused with fresh, heparinized rat blood (hematocrit 30%), with
      rat blood containing a vasodilator agent (sodium nitroprusside, 1 X 10(-3)
      mol/L), or with 2.5% bovine serum albumin in Krebs-Henseleit buffer (BSA-KH).
      Pressure-flow curves were constructed over an extended range of portal venous
      inflow (0 to 70 mL.min-1, corresponding to a flow rate per gram liver wet weight,
      Q, of approximately 0 to 7 mL.min-1.g-1). Subsequent analysis showed that two
      mathematical expressions adequately described the data over the full range of
      flow. Thus, the pressure-flow curve could be represented by (a) the sum of a
      linear plus a hyperbolic function, i.e., P = Q.R' + Pmax.Q/(Q + Km), where R',
      Pmax, and Km are constants, or (b) by the simple equation G = C.P, where G is the
      conductance (Q/P), and C is a conductivity constant. The values of R', Pmax, Km,
      and C were significantly different under each of the circumstances investigated,
      but the form of the curve was not altered. Hence, it is proposed that these
      parameters can be used to describe the fundamental hemodynamic properties of the
      portal vascular bed of the isolated rat liver. The results are discussed in terms
      of the microvascular recruitment and distensible resistance vessel models of the
      hepatic microcirculation.

PMID- 7806152
TI  - Evaluation of purine nucleoside phosphorylase release as a measure of hepatic
      endothelial cell injury.
AB  - With emerging data that endothelial cell (EC) injury is the limiting factor in
      liver preservation and hepatic function, a simple and reliable biochemical
      technique for monitoring EC injury is needed. Measurement of purine nucleoside
      phosphorylase (PNP) release into the circulation from perfused liver has been
      proposed as such a method. However, our experiments with perfused rat liver did
      not display a clear or direct relationship between PNP release and endothelial
      cell injury. Therefore, we re-examined the suitability of using PNP as a measure
      of nonparenchymal injury by measuring its distribution in purified populations of
      hepatocytes, ECs, and Kupffer cells (KCs) and correlating cell injury and enzyme
      release in short-term cultures at 37 degrees C of each cell type. Purified cells
      were incubated (4 x 10(6) cells/mL) in oxygen or nitrogen saturated. Wisconsin
      solution or Krebs buffer for 6 hours, with cell viability and PNP release assayed
      every 2 hours. ECs had the lowest specific activity (27 +/- 9 U/mg protein; mean
      +/- standard error of the mean [SEM]) compared with both hepatocytes (115 +/- 15)
      and KCs (66 +/- 18). Despite a decrement in EC and KC viability over time in each
      incubation solution, there was poor correlation between time of incubation and
      PNP release (r = .01 to .22), and between cell viability and PNP release (r = .01
      to .16). In contrast, PNP release from incubated hepatocytes correlated with the
      length of incubation (r = .57 to .78) as well as cell injury (r = .63 to .77) in
      all four test solutions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7806153
TI  - Structure and dynamics of the fenestrae-associated cytoskeleton of rat liver
      sinusoidal endothelial cells.
AB  - This article describes the cytoskeleton associated with fenestrae and sieve
      plates of rat liver sinusoidal endothelial cells. Fenestrae control the exchange
      between the blood and parenchymal cells. We present evidence indicating that
      several agents that change the fenestrae and sieve plates also cause changes in
      the cytoskeleton. Cultured liver endothelial cells (LECs) were slightly fixed and
      treated with cytoskeleton extraction buffer. Detergent-extracted whole mounts of
      cultured cells were prepared for either scanning electron microscopy (SEM) or
      transmission electron microscopy (TEM). Extracted cells show an integral
      intricate cytoskeleton; sieve plates and fenestrae are delineated by cytoskeleton
      elements. Fenestrae are surrounded by a filamentous, fenestrae-associated
      cytoskeleton with a mean filament thickness of 16 nm. Sieve plates are surrounded
      and delineated by microtubuli, which form a network together with additional
      branching cytoskeletal elements. The addition of ethanol to cultured cells
      enlarged the diameter for these fenestrae-associated cytoskeleton rings by 5%,
      whereas serotonin treatment reduced the diameter by 20%. These observations
      indicate that the fenestrae-associated cytoskeleton probably changes the size of
      fenestrae after different treatments. After treatment with cytochalasin B the
      number of fenestrae increased. However, cytochalasin B did not change the
      structure of the fenestrae-associated cytoskeleton ring, but disperses the
      microtubuli. In conclusion, LECs have a cytoskeleton that defines and supports
      sieve plates and fenestrae. Fenestrae-associated cytoskeleton is a dynamic
      structure and plays a role in maintaining and regulating the size of fenestrae
      after different treatments. Therefore, the fenestrae-associated cytoskeleton
      controls the important hepatic function of endothelial filtration.

PMID- 7806154
TI  - Concanavalin A-induced T-cell-mediated hepatic injury in mice: the role of tumor
      necrosis factor.
AB  - Concanavalin A activates T lymphocytes in vitro and causes T-cell-dependent
      hepatic injury in mice. T lymphocytes were previously identified as effector
      cells of concanavalin A-induced liver injury. Here we report that hepatic injury
      is characterized by apoptotic cell death. On concanavalin A challenge, the
      cytokines tumor necrosis factor-alpha (TNF alpha), interleukin-2, granulocyte
      macrophage-colony stimulating factor, and interferon-gamma were detectable in the
      circulation of the mice. Pretreatment of mice with anti-mouse TNF-alpha antiserum
      protected them from concanavalin A-induced liver injury. Nude mice failed to
      release TNF-alpha or interleukin-2 after concanavalin A challenge and were
      protected from liver injury. Lymph node cell transfer from responder mice to
      resistant nude mice resulted in susceptibility of the latter towards concanavalin
      A, i.e., to induction of cytokine release and hepatotoxicity. These experiments
      suggest that immunocompetent T cells play a pivotal role in concanavalin A
      stimulated TNF-alpha release in vivo. After intravenous administration of
      fluorescein isothiocyanate-labeled concanavalin A to mice, the most fluorescence
      was found within the liver. In vitro, concanavalin A stimulation of separate
      cultures of mouse lymph node cells or nonparenchymal liver cells induced the
      release of minute amounts of TNF, whereas stimulation of cocultures of these
      cells resulted in production of substantial amounts of TNF-alpha. These findings
      may explain the hepatotropic effect of concanavalin A. In conclusion, T-cell
      dependent concanavalin A-induced apoptotic liver injury in mice is related to
      immunological and cytokine-mediated disorders and possibly to autoreactive
      hepatic processes.

PMID- 7806155
TI  - Changes in fatty acid composition of plasma, liver microsomes, and erythrocytes
      in liver cirrhosis induced by oral intake of thioacetamide in rats.
AB  - The aim of this study was to evaluate the changes in fatty acid composition of
      lipids of plasma, erythrocytes, and liver microsomes in rats with liver cirrhosis
      induced by oral intake of thioacetamide and to determine to what extent the
      experimental model reproduces the fatty acid tissue alterations reported in human
      cirrhosis. Two groups of rats were studied. The control group received water ad
      libitum, and the experimental group received 0.03% w/v thioacetamide in drinking
      water for 2, 4, and 6 months. At these times, lipids of plasma, erythrocytes, and
      liver microsomes were extracted, and their fatty acid compositions were
      determined. Thioacetamide intake led to macronodular and micronodular cirrhosis
      at 2 months. These alterations progressed at 4 months and eventuated in liver
      tumors at 6 months. Thioacetamide-treated rats showed a drop in total plasma
      fatty acids, higher percentages of palmitic acid in all lipid fractions, and
      lower levels of stearic acid in erythrocyte lipids and liver microsomal
      phospholipids. Oleic acid increased in plasma cholesteryl esters and
      phospholipids, as well as in erythrocyte lipids and liver microsomal
      phospholipids. In plasma lipids and liver microsomal phospholipids, the
      percentages of arachidonic and docosahexaenoic acids decreased. The latter also
      decreased in erythrocyte lipids. In addition, liver microsomes showed a higher
      cholesterol/lipid phosphorus molar ratio. The experimental model of cirrhosis
      obtained by intake of thioacetamide in drinking water for 4 months reproduces
      many of the fatty acid tissue alterations that appear in human cirrhosis and may
      serve to ascertain the biochemical mechanisms involved in these changes.

PMID- 7806156
TI  - Feeding S-adenosyl-L-methionine attenuates both ethanol-induced depletion of
      mitochondrial glutathione and mitochondrial dysfunction in periportal and
      perivenous rat hepatocytes.
AB  - Mitochondrial glutathione plays an important role in maintaining a functionally
      competent organelle. Previous studies have shown that ethanol feeding selectively
      depletes the mitochondrial glutathione pool, more predominantly in mitochondria
      from perivenous hepatocytes. Because S-adenosyl-L-methionine (SAM) is a
      glutathione precursor and maintains the structure and function of biological
      membranes, the purpose of the present study was to determine the effects of SAM
      on glutathione and function of perivenous (PV) and periportal (PP) mitochondria
      from chronic ethanol-fed rats. SAM administration resulted in a significant
      increase in the basal cytosol and mitochondrial glutathione in both PP and PV
      cells from both pair-fed or ethanol-fed groups. When hepatocytes from ethanol-fed
      rats supplemented with SAM were incubated with methionine plus serine or N
      acetylcysteine, mitochondrial glutathione increased in parallel with cytosol, an
      effect not observed in cells from ethanol-fed rats without SAM. Feeding equimolar
      N-acetylcysteine raised cytosol glutathione but did not prevent the mitochondrial
      glutathione defect. In addition, SAM feeding resulted in significant preservation
      of cellular adenosine triphosphate (ATP) levels (23% to 43%), mitochondrial
      membrane potential (17% to 25%), and the uncoupler control ratio (UCR) of
      respiration (from 5.1 +/- 0.7 to 7.3 +/- 0.6 and 2.1 +/- 0.3 to 6.1 +/- 0.7) for
      PP and PV mitochondria, respectively. Thus, these effects of SAM suggest that it
      may be a useful agent to preserve the disturbed mitochondrial integrity in liver
      disease caused by alcoholism through maintenance of mitochondrial glutathione
      transport.

PMID- 7806157
TI  - Effect of deoxycholate on immunoglobulin G concentration in bile: studies in
      humans and pigs.
AB  - Because an increase in biliary deoxycholate levels seems to be a risk factor for
      cholesterol gallstone formation, we determined the relationship between
      deoxycholate levels and levels of the pronucleating protein, immunoglobulin G
      (Ig) in human gallbladder bile. Patients with cholesterol gallstones had a higher
      concentration of biliary IgG compared with a pigmented stone group and control
      patients. This was associated with the simultaneous presence of two conditions in
      the cholesterol stone group, supersaturated bile and a high deoxycholate/cholate
      ratio. The other patient groups met only one of the two conditions. Next, animal
      studies were performed to determine if model biles mimicking the two conditions
      could affect IgG secretion by the gallbladder. Gallbladders were exposed in vivo
      and then in an Ussing chamber to model biles. The voltage clamp technique was
      used to monitor functional integrity of the preparation. Three different model
      biles were tested: (1) taurodeoxycholate (TDC), 80%; taurocholate (TC), 20%; and
      cholesterol saturation index (CSI), 1.2; (2) TDC, 20%; TC, 80%; and CSI, 1.2; and
      (3) TDC, 80%; TC, 20%; and CSI, 0.6. IgG concentrations became significantly
      higher in group 1 than in the other two groups. The concentration of mucous
      glycoprotein was also significantly greater in group 1 when compared with group
      2. Plasma cells were increased in number in mucosal and submucosal layers in
      group 1. We conclude that cholesterol supersaturated model bile with high content
      of TDC induces gallbladder epithelial alterations, which increase the luminal
      concentration of IgG and mucous glycoprotein.

PMID- 7806158
TI  - UW-preservation of cultured human gallbladder epithelial cells: phenotypic
      alterations and differential mucin gene expression in the presence of bile.
AB  - In orthotopic liver transplantation, extended cold ischemia of the graft may
      induce cell damage, particularly in biliary epithelium. We have investigated the
      effects of a cold University of Wisconsin (UW) solution on cultured human
      gallbladder biliary epithelial cells (GBEC) exposed or not exposed to stagnant
      bile. In UW solution, morphological alterations of cultured GBEC were not
      prominent under light microscopy after 16 hours at 4 degrees C, being more
      striking after 24 to 48 hours. Ultrastructural examination of GBEC showed a
      condensation of chromatin at the periphery of the nuclei after 16 hours in cold
      UW solution. Both protein and DNA syntheses were strikingly reduced in these
      cells. After rewarming in standard Williams' medium at 37 degrees C for 24 hours,
      cultured GBEC exhibited both normal morphology and function. As in both freshly
      isolated and routinely cultured GBEC, rewarmed cells expressed various mucin
      genes, namely MUC1, MUC3, MUC4, MUC5AC, and MUC5B genes, whereas MUC2 mRNAs were
      barely detectable. A dramatic decline in the steady-state mRNA levels of both
      MUC3 and MUC5B was found in cultured GBEC versus freshly isolated cells. Addition
      of bile into UW solution at 4 degrees C had no significant effect on GBEC
      morphology and DNA and protein syntheses. When bile was added during the
      rewarming period, both protein and DNA syntheses were strongly reduced. Addition
      of bile during either storage in UW solution or rewarming period induced
      increased steady-state MUC2, MUC3 and MUC5AC mRNA levels.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7806159
TI  - Transforming growth factor-beta 1 regulates platelet-derived growth factor
      receptor beta subunit in human liver fat-storing cells.
AB  - Activated liver fat-storing cells (FSC) are known to play a key role in the
      development of liver fibrosis. An important element in FSC activation process is
      the increased expression of receptors for platelet-derived growth factor (PDGF),
      a potent mitogen for FSC. The aim of the present study was to evaluate the
      expression PDGF-receptor alpha and beta subunits in cultured human FSC and their
      regulation induced by transforming growth factor-beta 1 (TGF-beta), a cytokine
      potentially involved in an autocrine loop. TGF-beta induced a significant
      increase of the mitogenic effect of PDGF-BB and did not affect the mitogenicity
      of PDGF-AA and PDGF-AB, suggesting a selective action of the PDGF-receptor-beta
      subunit. This hypothesis was confirmed by regulation experiments showing
      selective and time-dependent upregulation of the messenger (m)RNA encoding for
      the PDGF-receptor-beta subunit and the relative protein induced by TGF-beta. In
      addition, binding studies showed a parallel increase of PDGF-BB binding sites
      after incubation of human FSC with TGF-beta. These studies provide evidence for
      an additional mechanism leading to the perpetuation of FSC activation and
      proliferation and contribute to a better understanding of the role of TGF-beta
      and PDGF in the development of liver fibrosis.

PMID- 7806160
TI  - Fulminant hepatic failure: summary of a workshop.
AB  - Fulminant hepatic failure (FHF) is defined by the appearance of severe liver
      injury with hepatic encephalopathy in a previously healthy person. There are an
      estimated 2,000 cases of FHF in the United States yearly, representing 0.1% of
      all deaths and, perhaps, 6% of liver-related deaths. The causes of FHF are many,
      the chief ones in the United States being hepatitis A; B; non-A, non-B and drug
      induced liver disease. There are no specific therapies for FHF, however, liver
      transplantation is recommended for situations in which spontaneous recovery
      appears unlikely. Factors that are valuable in assessing the likelihood of
      spontaneous recovery are static features such as patient age and etiology of FHF
      and dynamic features including encephalopathy grade, prothrombin time, and serum
      bilirubin. Presently, approximately 7% of all liver transplants are done for FHF
      and the 1-year patient survival rates average 63%, somewhat less than survival
      rates for nonfulminant liver disease, averaging 78%. The management of patients
      with FHF is challenging, particularly important being monitoring and early
      treatment of infections, hemodynamic abnormalities, and brain edema. Innovative
      approaches to management and therapy include use of cytoprotective or antiviral
      medications, hepatic support systems, extracorporeal liver support, hepatocyte
      transplantation, auxiliary liver transplantation, and xenotransplantation. None
      of these are of proven benefit, but many are promising as a means to support the
      patient with FHF until spontaneous recovery occurs or a suitable liver graft is
      available for transplantation.

PMID- 7806161
TI  - Primary biliary cirrhosis and bone disease.

PMID- 7806163
TI  - Shedding light into the black box of childhood cholestatic liver disease.

PMID- 7806162
TI  - non-ABCDE hepatitis: is there another enterically transmitted hepatitis virus?

PMID- 7806164
TI  - Bone marrow augmentation in solid organ transplantation--any conclusions?

PMID- 7806165
TI  - Insulin independent glucose uptake in cirrhosis.

PMID- 7806166
TI  - Severe or multiple rejection episodes are associated with early recurrence of
      hepatitis C after orthotopic liver transplantation.
AB  - Recurrent hepatitis C causes significant morbidity after liver transplantation.
      Because immunosuppression is associated with enhanced viral replication, we
      postulated that clinical recurrence of the disease may be associated with
      augmented immunosuppression for rejection. In 96 patients with hepatitis C who
      received liver transplants, we recorded the interval from transplantation to
      recurrence, the episodes of steroid-resistant rejection (SRR) requiring OKT3, the
      number of rejection episodes, and the use of OKT3 induction. Recurrence was
      diagnosed based on elevated transaminases and characteristic histology. Hepatitis
      C recurred in 43 of 96 patients. Fifteen of 21 patients (71.4%) who previously
      had SRR had recurrence, versus 28 of 75 patients (37.3%) who either had no SRR
      (72 patients) or had it after recurrence was diagnosed (3 patients) (P < .01).
      Mean time to recurrence was 127 +/- 31 days in the 15 patients who had had SRR
      versus 246 +/- 42 days in the other 28 patients (P = .02). Recurrence and number
      of rejection episodes were clearly associated: 6 of 33 patients (18.2%) with no
      rejection had recurrence (P < .05), versus 11 of 26 patients (42.3%) with one
      rejection episode (P < .05) and 26 of 37 (70.2%) with more than 1 episode (P <
      .05). OKT3 induction was used in 15 patients; 9 of 15 patients had recurrence
      (ns) at 337 +/- 95 days. Of 72 patients who initially received triple
      immunosuppression, 30 patients had recurrence at 186 +/- 25 days (P = .05). Nine
      patients received primary FK506; 4 had recurrence at 68 +/- 14 days.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7806167
TI  - Long-term effects of cholecystectomy on bile acid metabolism.
AB  - Comparative studies between different patient groups have suggested that
      cholecystectomy enhances bacterial dehydroxylation of the primary bile acid
      cholic acid (CA) to the secondary bile acid deoxycholic acid (DCA). DCA may exert
      a cocarcinogenic effect on the colonic mucosa. In a short-term follow-up study on
      nine female patients we found no alterations of the CA or DCA pools after
      cholecystectomy. However, in the long term, cholecystectomy could promote changes
      of the intestinal bacterial flora and thereby lead to enhanced conversion of CA
      to DCA, causing an expansion of the DCA pool size and a reduction of the CA pool
      size. To test this hypothesis, pool sizes, fractional turnover rates (FTR), and
      synthesis or input rates of CA, chenodeoxycholic acid (CDCA) and DCA were
      determined in 12 female patients before and again 5 to 8 years after
      cholecystectomy. In the long term, pool size and synthesis rate of CA had not
      changed and DCA pool size had expanded by only 7.5% (not significant [NS]). DCA
      input increased by 32% (NS) but was balanced by an increase in FTR of 36%. Pool
      size (-17%) and synthesis rate (-5%) of CDCA were not significantly diminished.
      Overall, the sizes of the total bile acid pool (-6%, NS; 50 +/- 8 vs. 53 +/- 13
      mumol/kg) and the pool fractions of CA (44.7 +/- 10.3% vs. 42.8 +/- 7.6%) and DCA
      (25.5 +/- 14.1% vs. 23.6 +/- 9.3%) remained similar. In conclusion,
      cholecystectomy causes no changes in bile acid pool composition and thus has no
      adverse effects on bile acid metabolism in the long term.

PMID- 7806168
TI  - Grading of cellular rejection after orthotopic liver transplantation.
AB  - All 684 post-orthotopic liver transplantation (OLT) liver biopsies performed at
      the Royal Free Hospital (RFH) between 1988 and 1993, from 120 patients, were
      reviewed in order to try to define the relative importance of the histological
      features of immunosuppression-responsive cellular rejection. Twenty histological
      features considered to be possible contributors to the diagnosis of cellular
      rejection were documented in a binary (present/absent) fashion. These features in
      106 biopsy specimens obtained 1 to 8 days after OLT were analyzed using stepwise
      logistic discriminant analysis. All clinical and treatment records were reviewed,
      and each biopsy specimen was assigned to a diagnostic category depending on these
      records and follow-up information. Important determinants of the histological
      diagnosis of cellular rejection (which occurred in 84 of the 106 cases) were
      moderate/severe mixed portal inflammation, eosinophils, endotheliitis, and bile
      duct damage. When these all occurred together, the odds of rejection increased
      3.6-fold. The original histological diagnosis was recorded, and each biopsy
      specimen showing cellular rejection was regarded according to the specific
      criteria of Snover et al., Demetris et al., and a novel RFH scoring system. The
      latter consists of evaluating portal inflammation, endotheliitis, eosinophils,
      and bile duct damage, each on a 0 to 3 scale (none, mild, moderate, or severe,
      respectively) and summation. The resulting cellular rejection score thus can
      range from 0 to 12. The agreement between the different scoring systems was
      analyzed using K statistics, and there was good concordance (K, 0.64 to 0.78),
      despite different histological criteria being used to derive each score. Each
      system showed a similar degree of sensitivity (87% to 96%). The specificity
      ranged from 59% to 77%. We conclude that the histological diagnosis of cellular
      rejection relies mainly on the previously described features of mixed portal
      inflammation, endotheliitis, eosinophils, and duct damage. There is scope for
      unification and simplification of the existing grading systems, which depend on
      differing criteria, and we suggest one such scheme.

PMID- 7806169
TI  - Anti-liver cytosolic antigen type 1 (LC1) antibodies in childhood autoimmune
      liver disease.
AB  - Antibodies to liver cytosol antigen type 1 (anti-LC1), which recognize a 60-kd
      peptide contained in the liver cytosolic fraction, have been reported to define a
      subset of autoimmune hepatitis (AIH) either negative for other autoantibodies or
      positive for anti-liver kidney microsomal antibody type 1 (LKM-1) and to be best
      detected in immunodiffusion. To analyze the prevalence of anti-LC1 in childhood
      liver disease, we have tested the sera of 95 patients using immunoblot, indirect
      immunofluorescence, and immunodiffusion. Fifteen children had smooth muscle
      antibody (SMA) and/or anti-nuclear antibody (ANA)-positive AIH, 13 had anti-LKM-1
      positive AIH, 14 had autoimmune sclerosing cholangitis (ASC) (all SMA and/or ANA
      positive), and 53 had non-autoimmune liver disease (10 had alpha 1-anti-trypsin
      deficiency [alpha 1-ATD], 11 had Wilson's disease [WD], 14 had Alagille's
      syndrome, and 18 had chronic hepatitis B virus [HBV] infection). Twenty healthy
      children were studied as controls. Anti-LC1 positivity in immunodiffusion and
      strong reactivity in immunoblot were found in 4 LKM-1- and 2 SMA/ANA-positive
      patients with AIH and in 1 patient with ASC, but in none of the patients with
      other liver diseases nor in controls. A weak 60-kd band was detected by
      immunoblot in 6 more patients with AIH (2 were LKM-1- and 4 were SMA/ANA
      positive) and 6 patients with ASC, all anti-LC1-negative by immunofluorescence
      and immunodiffusion. No distinct clinical features characterized the anti-LC1
      positive patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7806170
TI  - A simple modification in operative technique can reduce the incidence of
      nonanastomotic biliary strictures after orthotopic liver transplantation.
AB  - Nonanastomotic strictures after liver transplantations are a source of
      significant morbidity, often necessitating retransplantation. The purpose of this
      study was twofold: first to identify features associated with the development of
      this lesion; second, to make technical modifications that will decrease the
      incidence of this problem. In the first part of this study, 15 of 131 patients
      were diagnosed with nonanastomotic biliary stricture. A stepwise logistic
      regression analysis associated donor cold ischemic time and dopamine dose with
      the development of nonanastomotic biliary strictures. All these patients had
      arterial reconstruction after partial revascularization of the liver with portal
      venous blood. Because the bile duct receives its blood supply from only the
      hepatic artery, we hypothesized that the prolonged period of warm ischemia from
      staged reconstruction of the vascular supply would promote the development of
      this lesion. In a second part of this study, the stricture rate in 45 patients
      with simultaneous revascularization using both the hepatic artery and portal vein
      was compared with that in 83 patients from the first part of this study initially
      revascularized with portal venous blood. All patients in the second study had
      grafts preserved using UW solution. Only 1 patient with simultaneous
      revascularization developed a nonanastomotic biliary stricture. Because we were
      unable to identify any significant complications related to this method of
      revascularization, we propose that the hepatic artery and portal vein should be
      released simultaneously, especially in patients receiving a graft with prolonged
      storage time.

PMID- 7806171
TI  - Occurrence of hepatocellular carcinoma and decompensation in western European
      patients with cirrhosis type B. The EUROHEP Study Group on Hepatitis B Virus and
      Cirrhosis.
AB  - To examine the morbidity of compensated cirrhosis type B, a cohort of 349 Western
      European, white patients (86% men; mean age, 44 years) with biopsy-proven
      cirrhosis was followed up for a mean period of 73 months and was studied for
      occurrence of hepatocellular carcinoma (HCC) and decompensation. At entry into
      the study all patients were tested for hepatitis B e antigen (HBeAg; 34% of
      patients were HBeAg-positive) and antibody to hepatitis delta virus (anti-HDV;
      20% of patients were anti-HDV-positive); 48% of 252 patients tested were
      hepatitis B virus (HBV)-DNA-positive. During follow-up HCC developed in 32 (9%)
      of the 349 patients and decompensation was observed in 88 (28%) of 317 tumor-free
      patients. Five years after diagnosis, the probability of HCC appearance was 6%
      and the probability of decompensation was 23%. After the first episode of
      decompensation the probability of survival was 35% at 5 years. Cox's regression
      analysis identified three variables that independently correlated with HCC: age,
      serum levels of platelets, and liver firmness on physical examination. HBV (HBeAg
      or HBV-DNA) and HDV (anti-HDV) markers at presentation had no prognostic value
      for the development of HCC. In conclusion, a high proportion of patients with
      HBsAg-positive compensated cirrhosis do not experience worsening of their
      condition for several years, but once decompensation occurs life expectancy is
      poor. European, white patients with compensated cirrhosis type B are at
      consistent risk for HCC. Prognostic factors for HCC reflect an advanced stage of
      cirrhosis and support the hypothesis that development of a tumor could be the
      likely consequence of long-standing hepatic disease.

PMID- 7806172
TI  - Selective transmission of variant genomes from mother to infant in neonatal
      fulminant hepatitis B.
AB  - Hepatitis B virus (HBV) nucleotide sequences isolated from mother/child pairs
      were analyzed in three cases of neonatal fulminant hepatitis B (FHB).
      Heterogeneous HBV sequences consistent with both adw2 and ayw subtype were found
      in all three mothers. In one case, in which the child survived, both subtypes
      were transmitted. By contrast, only the ayw subtype was present in the two other
      children with a fatal course of FHB. In one fatal case, studied in greater
      detail, multiple HBV variants (viral quasi-species) were identified in both
      mother and child. A direct sequence comparison showed that only a subfraction of
      the virus pool from the mother was transmitted and that multiple new mutations
      emerged in the child. These data suggest that a minor HBV subpopulation from the
      mother may prevail as the dominant species in the child and that neonatal FHB is
      associated with the selection of mutant strains.

PMID- 7806173
TI  - Noninvasive measurement of femoral blood flow and portal pressure response to
      propranolol in patients with cirrhosis.
AB  - This study investigated the correlation between changes in hepatic and systemic
      hemodynamics and femoral blood flow (FBF), measured by dual-beam pulsed wave
      Doppler, in 58 portal hypertensive patients receiving propranolol (0.15 mg/Kg
      intravenously; n = 44) or placebo (n = 14) under double-blind conditions. Placebo
      administration had no effects. Propranolol caused significant reductions (P <
      .0001) in hepatic venous pressure gradient (HVPG; from 19.1 +/- 4.1 to 16.2 +/-
      4.2 mm Hg), azygos blood flow (from 563 +/- 204 to 387 +/- 176 mL/min), cardiac
      index (CI; from 4.4 +/- 1.0 to 3.3 +/- 0.8 L/m2/min), and FBF (from 237 +/- 79 to
      176 +/- 58 mL/m2/min). In 17 patients HVPG decreased below 12 mm Hg and/or more
      than 20% of the baseline value (good response; mean change, -26 +/- 8%); in the
      remaining 27 patients (poor response) the mean change in HVPG was less: -9 +/-
      6%. Patients with a good response had bled less often from varices, had
      significantly higher FBF (272 +/- 73 vs. 215 +/- 76 mL/m2/min) and lower baseline
      HVPG (16.8 +/- 3.9 vs. 20.6 +/- 3.6 mm Hg) than those with poor response in HVPG.
      The good response was also associated with greater decreases in FBF (-33 +/- 12
      vs. -19 +/- 13% in poor responders), CI (-30 +/- 9 vs. -19 +/- 12%), and heart
      rate (-19 +/- 5 vs. -16 +/- 6%). A decrease in FBF of > 20% predicted a good
      response in 16 of 28 patients (positive predictive value, 57%).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7806174
TI  - Metabolism of cholesterol and low- and high-density lipoproteins in primary
      biliary cirrhosis: cholesterol absorption and synthesis related to lipoprotein
      levels and their kinetics.
AB  - Cholesterol absorption, elimination, and synthesis, and low-density lipoprotein
      (LDL) and high density lipoprotein (HDL) kinetics were studied in patients with
      mild to severe primary biliary cirrhosis (PBC) (n = 16) to show how this
      cholestatic disease modified cholesterol and lipoprotein metabolism as compared
      with healthy controls (n = 50). Serum total and lipoprotein cholesterol and
      triglyceride levels were similar in the two groups, but in PBC, especially in
      severe forms, very low density lipoprotein (VLDL) was rich in apoprotein (apo) B
      and cholesterol and low in triglycerides, whereas LDL was rich in triglycerides
      and low in esterified cholesterol, and HDL was enriched by surface lipids,
      phospholipids, and free cholesterol. In severe PBC, the fractional catabolic rate
      (FCR) for LDL apo B was reduced. The transport rate (TR) for LDL apo B was
      unaffected and it tended to correlate with the LDL apo B and LDL cholesterol
      levels in PBC, whereas in the controls the LDL apo B concentration was regulated
      by both the FCR and TR, and LDL cholesterol was regulated only by FCR. FCR for
      apo A-I in HDL was unaltered in PBC, but TR for apo A-I was reduced in the severe
      cases. Cholesterol absorption efficiency was significantly reduced in PBC (14.5
      +/- 3.0% in severe PBC and 34.0 +/- 2.5% in mild PBC vs. 47.4 +/- 1.4% in the
      controls, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7806175
TI  - Failure of hepatopulmonary syndrome to resolve after liver transplantation and
      successful treatment with embolotherapy.
AB  - The hepatopulmonary syndrome is an uncommon accompaniment of chronic liver
      disease. The outcome of this disorder after orthotopic liver transplantation is
      variable. We describe a patient with the hepatopulmonary syndrome who underwent
      orthotopic liver transplantation for autoimmune hepatitis. Her platypnea and
      orthodeoxia failed to improve postoperatively. Pulmonary angiography showed large
      pulmonary arteriovenous shunts that were successfully treated with coil
      embolotherapy.

PMID- 7806176
TI  - Nursing's role in the nutritional care of the terminally ill: weathering the
      storm.
AB  - The role of the nurse in nutritional care of the terminally ill is first, to come
      to terms with personal, psychological, and moral and ethical issues surrounding
      nutrition and hydration on an individual level; and second, to enter into a
      partnership with the patient and family and guide them through the storm of
      emotions and questions using a framework based on principles of ethics, crisis
      intervention, and effective communication. The nurse's ability to be present with
      the patient and family during this time is his/her primary tool as the nurse
      helps them maintain wellness and equilibrium.

PMID- 7806177
TI  - Enteral and parenteral nutrition support of terminally ill patients: practical
      and ethical perspectives.
AB  - The ethics of dealing with the provision of nutrition has been greatly
      complicated by technological advances. Seventy percent of all deaths in the
      United States include a decision to forgo some life-sustaining treatment
      including nutrition support. This article reviews ethical issues in nutrition
      support, appropriate and inappropriate nutrition support, practical information
      regarding provision of nutrition, and the development of institutional policies
      regarding artificial nutrition and hydration. Communication is emphasized in the
      process of establishing an ethically defensible consensus between patient and
      caregiver regarding withholding or withdrawing nutrition support. Within this
      context, withholding and withdrawing this support are considered to have the same
      ethical significance. Artificial nutrition and hydration is considered medical
      therapy and can be refused by competent patients and surrogates of incompetent
      patients under certain circumstances. Patient autonomy is emphasized as a guiding
      ethical principle.

PMID- 7806178
TI  - Legal decisions affecting the limitation of nutritional support.
AB  - The withholding of nutritional support from patients is one of the most
      controversial issues in modern medical ethics and law. Withholding support from a
      consenting, terminally ill patient is the simplest case situation to defend, but
      patients in a persistent vegetative state or irreversible, chronic illness,
      require more careful deliberation. Regarding this issue, five primary principles
      have been utilized in legal decision making. These include: futility, autonomy,
      integrity of health professionals, states interests, balancing benefits versus
      harm and quality of life. The two landmark legal cases which have set the tone
      for most other court decisions are Paul Brophy and Nancy Beth Cruzan. Both cases
      clarified the right of competent adults to refuse nutritional support, even if
      life-saving. In the Cruzan case, however, states were given the authority to
      request clear and convincing evidence for the previous wishes of the incompetent
      patient. In summary, competent patients entering a hospice program should make
      informed decisions about their desires for feeding, as they do with other
      treatment decisions. Optimally, those wishes should be codified into an advance
      directive and a proxy decision maker named. If a patient is not competent, and
      without previously expressed wishes, immediate family members are usually
      consulted for what they believe are the patient's best interests. Last, although
      limitations of care for terminally ill children fall under the same general
      guidelines as for adults, the "Baby Doe Rules" are a complicating factor.

PMID- 7806180
TI  - Nutritional care of the terminally ill adult.
AB  - Nutrition and hydration options are based on many considerations that arise
      during the various phases of the dying process. This paper includes discussion of
      the psychological issues affecting intake, assessment techniques to determine
      whether nutrient intake is adequate, feeding suggestions for the caregiving
      family, and some guidelines for routine and complex care of the terminally ill
      adult. The ultimate goal is to improve quality of life for each terminally ill
      individual through a focus on patient benefit and patient care.

PMID- 7806179
TI  - Nutrition and hydration in the terminally ill cancer patient: the nurse's role in
      helping patients and families cope.
AB  - Cancer patients and their family members must cope with multiple losses as the
      disease progresses. The loss of ability to eat and drink is a real and perceived
      harbinger of the ultimate loss: death. While health care professionals know that
      these physiologic changes are a normal part of the dying process, families are
      rarely able to accept them easily. Because these losses have such profound
      emotional, spiritual, and physical ramifications, it is important that staff be
      prepared to provide appropriate support and information to patients and families.
      The suggestions posed in this article may be utilized by all members of the
      interdisciplinary team.

PMID- 7806181
TI  - Caring for the dying child.
AB  - In this paper we discuss the nutritional needs of terminally ill children. We
      delineate the physical, psychological, and developmental characteristics of
      children that differentiate them from adults vis a vis the nutritional aspects of
      their care. We highlight the special role of parents and suggest guidelines for
      dealing with the common nutritional needs of the dying child. We discuss ethical
      issues emphasizing the Baby Doe regulations, decision making for minors, and the
      benefits and burdens associated with permanently unconscious children.

PMID- 7806182
TI  - Appetite stimulants in terminal care: treatment of anorexia.
AB  - Anorexia is a common problem in terminally ill patients. The loss of appetite
      brings with it physical, psychological, and social problems. Effective treatment,
      therefore, should be multidimensional. The pharmacist is well-positioned to
      evaluate the appropriate use of medications for their effects on appetite, weight
      gain, mood, nausea, and anorexia. Studies have demonstrated that megestrol
      acetate has the most positive results in patients with advanced cancer and human
      immunodeficiency virus. Other medications studied have a less significant impact.
      Total parenteral nutrition can also sustain meaningful life for many terminally
      ill patients, but it is rarely successful in alleviating the anorexia associated
      with terminal illness.

PMID- 7806183
TI  - Maximizing foodservice in an inpatient hospice setting.
AB  - The philosophy of maximizing patient comfort and enhancing quality of life
      impacts on all aspects of foodservice in an inpatient hospice setting. The
      foodservice department's focus in the palliative care environment is to meet
      patients' physical, psychological, and social needs. The menu incorporates
      variety and comfort foods to meet the special requests of hospice patients. Food
      production and delivery provides for flexibility in meal preferences and meal
      serving times. Finally, sanitation standards and inservice training extend beyond
      the main foodservice operation to include the hospice "family" kitchen to protect
      the hospice patient from food-borne infections.

PMID- 7806184
TI  - [Study on antibacterial protein from human urinary bladder mucosa].
AB  - Acid-soluble extract of human bladder mucosal surface was obtained by washing out
      the bladder of accidentally dead male human with 1% acetic acid in the presence
      of proteinase inhibitors. Acid urea polyacrylamide gel electrophoresis (AU-PAGE)
      indicated that the acid-soluble extract had more than 10 main protein bands, but
      the currently known antibiotic peptides, e. g., Lysozyme and defensins, were not
      found in this extract. The quantitation assay of lysozyme showed that lysozyme
      only amounted to 2.2 microgram per milligram protein. When tested for
      antibacterial activity by using ultrasensitive radial diffusion assay, the acid
      soluble extract effectively killed E. coli ML-35P. The antibacterial activity of
      the acid-soluble extract was further analysed by gel overlay technique and the
      result showed that one main protein band, which was referred to as human bladder
      protein (HBP), was potently antibacterial against E. coli ML-35P. The HBP
      accounted for 4% of the total acid-soluble extract protein. These results suggest
      that the presence of antibacterial protein in the bladder mucosa may be the
      molecular base of the bladder antibacterial defence mechanisms.

PMID- 7806185
TI  - [Comparative study of organ storage solutions for rat liver preservation: effects
      of HX and Collins I solution on sinusoidal lining cells and hepatic functions].
AB  - The liver sinusoidal lining cell injury and biochemical function changes were
      studied with isolated perfusion after rat livers had been preserved in HX
      solution or in Collins II solution. Seventy inbred Wistar rats were randomly
      divided into control group (n = 10), group H (preserved with HX solution, n =
      30), and group C (preserved with Collins II solution, n = 30). The effects of the
      storage solutions were assessed by measuring the sinusoidal lining cell mortality
      (SLCM), Krebs-Henseleit perfusate ketone body ratio (PKBR), the hepatic sugar
      release (SL), and the number of livers secreting bile during isolated perfusion.
      The results suggest that the HX solution be much superior to Collins II solution
      in preventing sinusoidal lining cell injury and maintaining normal hepatic
      functions.

PMID- 7806186
TI  - [Effect of hemorheological factors on coronary flow during myocardial ischemia].
AB  - Intracoronary infusion of some drugs may induce superimposed coronary
      vasodilation upon endogenous vasodilation during myocardial ischemia, which was
      suggested as coronary vasodilator reserve. For an investigation of this
      phenomenon, 8 pigs were anesthetized, chest-opened, LAD (left anterior descending
      coronary artery)-dissected and instrumented. The LAD pressure was reduced to 4.67
      kPa (35mmHg), and then intracoronary infusion of adenosine, saline, or
      anisodamine (at the same rate of 2ml/min) was started and maintained for 9
      minutes. The three solutions all produced a significant increase in the coronary
      flow, including the saline (compared with the control, P < 0.05). The
      hemorheological examination of the distal coronary blood revealed a reduced
      hematocrit, plasma viscosity and whole blood viscosity during the saline and
      anisodamine infusion periods (P < 0.05), but in the adenosine infusion, the
      statistical analysis on hemorheological data revealed no significance compared
      with the control (P > 0.05). The results showed that the coronary vasodilator
      reserve induced by intracoronary drugs during myocardial ischemia might be partly
      accounted by regional hemodilution in the LAD bed. The study suggested that a
      decrease in blood viscosity might play an important role in the improvement of
      the narrowed coronary circulation, even more important than vasodilator drugs.

PMID- 7806187
TI  - [125I-alpha-sec-butyl-p-hydroxybenzyl alcohol receptor competitive binding assays
      in animal body].
AB  - Based on the receptor competitive binding assays in the mice and rat body, it has
      been proved that both diazepam and alpha-sec-butyl-p-hydroxybenzyl alcohol (G
      018) can inhibit 125I-G-018 binding with brain benzodiazepine receptor.
      Inhibiting effects were obvious in the cortex, cerebellum, hippocampus and
      midbrain. But in the medullao blongata and hypothalamus no inhibiting effect was
      observed. Experimental results have demonstrated that the inhibiting effect is
      consistent with distribution of benzodiazepine receptor in the brain. Also,
      experimental results have shown no difference between in vitro and in vivo. The G
      018 binding with benzodiazepine receptor has been clarified under physiologic
      conditions.

PMID- 7806188
TI  - [Study on phagocytosis of human neutrophils in diabetics].
AB  - Infection is one of the most common complications in diabetes mellitus (DM). The
      neutrophil plays an important role in the anti-infection mechanism. A comparative
      study on phagocytosis of P. Aeruginosa by human neutrophils in diabetic patients
      and healthy volunteers was carried out by means of the monolayer of neutrophils
      and ultrastructural observation in electronic microscopy. The results showed that
      the rates of phagocytosis, index of phagocytosis and rates of microbe lysis in DM
      group were much lower than those in normal controls (P < 0.01). The
      ultrastructure of neutrophils in diabetic patients became apparently abnormal
      during the process of neutrophil phagocytosis. The results demonstrated that the
      impairment in phagocytosis of neutrophils may be one of the causes of severe and
      repeated infection in diabetics.

PMID- 7806190
TI  - [Pathological study of enamel caries produced by oral bacteria in vitro].
AB  - The authors used the bacterial culture method to study early enamel caries-like
      lesions in vitro. Pathologic changes in the lesions were observed under polarized
      light microscope and scanning electron microscope. The results showed that this
      method could simulate the destructive procedures in carious development. The
      destructive way and pathologic changes of the caries-like lesions were very
      similar to those of natural caries. Under microscope, the ultrastructures of the
      relatively intact layer of the enamel surfaces were already changed. The prisms
      in the enamel surfaces were destroyed, and dissolved to form small pores. The
      pores could be an important path of the carious development.

PMID- 7806189
TI  - [Immunohistochemical study on fibrin in brain traumas].
AB  - The fibrin formation in brain traumas was studied by immunohistochemical method.
      Eleven cases of brain trauma were examined. The fibrin was demonstrated not only
      in the areas of brain contusion and the neuronal cytoplasm of hypothalamus,
      thalamus, brainstem, and cerebellum, but also on the membrane of endothelial
      cells and red blood cells within some capillaries. The fibrin was also found
      around capillaries and the areas far from the brain trauma. It was suggested that
      injuries to the brain occurred not only in the local areas of the brain subjected
      to the violence, but also in the areas far from the local injury. It meant that
      the brain injuries were not local, but diffuse. The fibrin observed in the
      neuronal cytoplasm, and on the membrane of endothelial cells and red blood cells
      within some capillaries was a sign of ante mortem brain traumas. The combined HE
      staining and immunohistochemical staining of the fibrin is useful in the
      demonstration of simple brainstem traumas.

PMID- 7806191
TI  - [Synthesis of terephthalic acid derivatives and their activity on human
      promyelocytic leukaemia cells HL-60].
AB  - There were 13 derivatives of terephthalic acid were synthesized, in which 9
      compounds were not found in literature. The 9 compounds were evaluated for their
      differentiation-inducing activities on human promyelocytic leukaemia cells HL-60.
      Compounds N1 and N4 possessed potential activity. Their percentage of
      differentiating effect was 55% (5 x 10(-6) mol/L), but it was less than that of
      retinoic acid (79%, 10(-7) mol/L).

PMID- 7806192
TI  - [Effects of gamma-aminobutyric acid and bicuculline on the spontaneous discharge
      of the nucleus paragigantocellularis lateralis neurons in brainstem slices in
      rat].
AB  - The effects of iontophoretic application of gamma-aminobutyric acid (GABA) and
      its antagonist, bicuculline (BIC) on the spontaneous discharge of
      paragigantocellularis lateralis (PGCL) neurons and the influence of BIC on the
      effects of GABA were studied in brainstem slice in rat with multibarrel
      microelectrode techniques. Both GABA and BIC showed three types of effects, i.e.,
      excitatory, inhibitory and unaffected; the percentage of each is 56.10%, 31.70%,
      12.20% (for GABA) and 66.67%, 5.88%, 27.45% (for BIC) of the tested neurons,
      respectively. The inhibitory effect of GABA and excitatory effect of BIC are dose
      dependent. In most of the neurons tested the response to GABA could be blocked by
      BIC. The results at cellular level suggest that there is endogenous GABA in PGCL
      and that there exists GABAA receptors on some of the PGCL neurons.

PMID- 7806193
TI  - [Intracellular recordings and electrophysiological properties of neurons of
      pancreatic ganglia in vitro].
AB  - The work was carried out to investigate electrophysiological properties of
      neurons of cat intrapancreatic ganglia in vitro by means of intracellular
      recordings. The mean value of resting membrane potential was -58.5 +/- 8.7 mV
      (chi +/- s chi, n = 35) with a range from -45 to 72 mV. The mean values of
      membrane input resistance (Rm), time constant (tau) and capacity (Cm) were 68.6
      +/- 5.1M omega, 3.4 +/- 0.2 ms and 50.8 +/- 3.9pF (n = 28), respectively. When
      depolarizing electrotonic potentials induced by intracellular injection of
      depolarizing current pulses (0.05-0.5nA, 5ms) reached the threshold potential
      level, all of the neurons could fire action potentials. The threshold, amplitude,
      overshoot and duration of spikes were 19.2 +/- 0.5mV, 81.0 +/- 1.7mV, 22.6 +/-
      0.9mV and 2.9 +/- 0.1ms (n = 35), respectively. The spike was followed by a
      prolonged after spike hyperpolarization with amplitude of 20.5 +/- 0.8mV (n =
      35). In most of neurons, fast excitatory postsynaptic potentials (f-EPSP) or
      orthodromic action potentials were recorded during stimulation of nerve trunks
      attached to the intrapancreatic ganglia. The mean values of amplitude, duration
      of the f-EPSP and conduction velocity of the nerves were 8.9 +/- 0.7mV, 25.8 +/-
      1.9ms and 0.48 +/- 0.04m/s (n = 24), respectively. The ongoing synaptic activity
      was observed in all of cells. Moreover, f-Epsp, was induced by acetylcholine
      mediated through nicotinic receptors.

PMID- 7806194
TI  - [Studies on the mechanism of Polyactin A's enhancive effect on NK cell activity].
AB  - It has been shown that the novel immunopotentiator Polyactin A (PAA) developed in
      China can augment NK cell activity. In order to further understand the mechanism
      of PAA effect on NK activities, we measured the binding and lytic capacities of
      peripheral blood lymphocytes (PBL) isolated from normal subjects and patients
      with esophageal carcinoma against K562 target cells by using a single cell
      cytotoxicity assay. Morphologically the ultrastructures of NK cells of normal
      subjects and the patients on PAA were also studied. The results showed that: (1)
      Preincubation PBL of normal subjects on PAA at 100 micrograms/ml for 4 hours
      could increase the rate of NK lysis with no effect on the binding rate. The
      binding capacities of PBL of patients with esophageal carcinoma were lower than
      those of normal subjects. Pretreatment PBL of patients with esophageal carcinoma
      could significantly increase not only the rate of NK lysis, but also the binding
      rate. (2) Study on the processes of conjugation and cytolysis by using light
      microscopic morphology, scanning electron microscopy (SEM) and transmission
      electron microscopy (TEM) found that effector cells include not only large
      granular lymphocytes (LGL), but also non-LGL bound to target cells. One effector
      cell could simultaneously make contacts with more than one target cell. It was
      found that PBL/K562 contacts could be morphologically divided into two types in
      the SEM and TEM. Either effector cell protrusions were pushed deep into pouches
      and lacunae of the target cell surface or a wide area of intimate cell-to-cell
      contact was formed. Effector/target cell contact is a prerequisite for NK lytic
      activity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7806195
TI  - [Study on red blood cell immune adherence function in coriaria lactone-induced
      epileptic seizure rats].
AB  - The immune adherence function of red blood cells in 17 rats was studied. It was
      found that the rosette rate of red blood cell C3b receptor (RBC-C3bRR) was 7.45
      +/- 1.36% in the epilepsy group (8 rats), and 10.84 +/- 1.77% in the control
      group (9 rats); and that the rosette rate of red blood cell immune complex (RBC
      ICR) was 7.42 +/- 2.62% in the epilepsy, and 10.80 +/- 1.72% in the control. As
      compared with the control group, the rosette rate of red blood cell C3b receptor
      was remarkably decreased in the epilepsy group (P < 0.05). There was no
      significant difference between the two groups in RBC-ICR. The results from this
      study demonstrated that the CL-induced seizures might result in decrease in red
      blood cell immune adherence function of the epilepsy rats.

PMID- 7806196
TI  - [Experimental study on the effect of ipriflavone against osteoporosis in
      ovariectomized rats].
AB  - In order to evaluate the effect of Ipriflavone (BO, synthesized for the first
      time by the School of Pharmaceutical Sciences of WCUMS) against osteoporosis in
      ovariectomized (OVX) rats, 98 female Wistar rats were divided into 7 groups:
      bilateral OVX, sham operated (S), and 5 treatment groups after OVX, of which 3
      groups were given domestic BO-25, 100, and 400 mg/kg BW (L, M, H), respectively,
      and the remaining two groups, BO (made in Japan)-100 mg/kg BW (J) and 17 beta
      estradiol-4 mg/kg BW (E). One day after operation, BO and E were given daily and
      twice a week, respectively, by gavage to the animals, while S and OVX groups were
      treated with vehicles alone. On the 14th and 6th day prior to the sacrifice 0.25%
      tetracycline hydrochloride was administered i.p. to 6 rats of each group at a
      dosage of 25 mg/kg BW. The rats were sacrificed after 12 wks and blood samples
      were collected for serum Ca, P, and AkP activity. The uterines were removed and
      weighed. Undecalcified sections of the left proximal tibia were processed for
      bone histomorphometry, and HE sections of the right tibia were processed for bone
      pathology. The weights per unit bone length, the calcium and phosphorus contents
      of the left femur were measured. The results showed that in the OVX animals
      trabecular bone volume, trabecular thickness, and the ash content of bone were
      all significantly reduced. This bone loss was associated with increase in
      osteoclast index, osteoblast index, osteoid surface and serum AkP
      activity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7806197
TI  - [Effects of fibronectin on cell attachment and migration of human tongue squamous
      cancer line Tca8113].
AB  - By using the cell culture technique in vitro, quantitative studies were carried
      out to test the effects of fibronectin (FN) on cell biological behaviour of human
      tongue squamous cancer line Tca8113 in terms of cell attachment to rat-tail
      collagen substrata supplemented with different concentration of FN or/and anti-FN
      serum as well as cell migrating distance from the agarose drop cultured with
      different media containing FN or/and anti-FN serum. The results displayed that FN
      could increase the density of cells attached to collagen substrata; the cell
      attachment was dose-dependent on FN. In addition, cell migration from the agarose
      drop might be induced and cell motility might be promoted by FN. Anti-FN serum
      could abolish or weaken the above-mentioned FN effects.

PMID- 7806198
TI  - [A primary study of the factors related to the patients' adherence of anti
      hypertensive therapy].
AB  - An interview covering demographic information, history of hypertension as well as
      medical and health-related questions was conducted on 540 hypertension patients
      in Chengdu. The objective of the study was to analyse the factors related to the
      adherence to antihypertensive therapy of these patients. The simple analysis
      showed that the education level of the patients, the type of payment for visiting
      physician, the convenience of visiting physician, the awareness of the severity
      of hypertension, the average family income of the patients were related to the
      adherence to therapy. The step multi-regression analysis showed that the type of
      payment for visiting physician, the convenience of visiting physician and the
      average family income were related to the adherence to antihypertensive therapy.

PMID- 7806199
TI  - [The mechanism and clinical significance of decreased anion gap in patients with
      COPD and acid-base imbalance].
AB  - The blood-gas and electrolytes of 427 blood samples from patients with COPD and
      acid-base imbalance were analysed. The results showed that 14 types of acid-base
      imbalance were present in patients with COPD and the anion gap decreased in 8
      types of acid-base imbalance, especially in respiratory acidosis, metabolic
      alkalosis and coexistence of both. The anion gap in respiratory acidosis and
      metabolic alkalosis were 0.8 +/- 6.6mmol/L and 2.1 +/- 7.3mmol/L, respectively.
      The anion gap in respiratory acidosis with metabolic alkalosis was negative. In
      all patients the HCO3- increased, and the total anion and total cation
      diminished. The anion gap decreased owing to the diminution of unmeasured anion.
      Clinically, the criterion for judging metabolic acidosis with increased anion gap
      is a value of anion gap over 16 mmol/L. But in case respiratory acidosis (or
      metabolic alkalosis) and metabolic acidosis coexist in a patient, the anion gap
      for judging metabolic acidosis should be decreased appropriately.

PMID- 7806200
TI  - [Resection of the caudate lobe of the liver].
AB  - It is difficult and dangerous to remove the caudate lobe of the liver because it
      not only is deeply embedded between the hilar structures of the liver and
      inferior vena cava but has its own independent vascular and biliary systems also.
      Two successful cases of caudate lobe resection are reported with review of
      literature and discussions on its applied anatomy, image-diagnosis, indications
      on surgery, technique and method of caudate lobe resection.

PMID- 7806201
TI  - [Clinical application of rhombotrapezious island musculocutaneous flap for skull
      base and/or craniomaxillary operation with malignant tumor].
AB  - Regional pedicled musculocutaneous flaps are the mainstay of the head and neck
      reconstruction. They provide a rapid, highly reliable and single-staged technique
      that is applicable in most cases. The rhombotrapezious island musculocutaneous
      flap is valuable in the base and craniomaxilloface reconstruction. In this study
      we updated our experience with the rhombotrapezious island musculocutaneous flap
      (RTIMF) in 6 cases from 1989 to 1993. Dissections were performed on 9 cadavers, 4
      preserved and 5 fresh, yielding 18 pairs or dorsal scapular and transverse
      cervical artery for evaluation. In the five fresh cadavers, the arteries were
      selectively cannulated and injected with colored latex. 67% with dorsal scapular
      and transverse cervical artery commonly arose from the thyro-cervical trunk. 33%
      with the dorsal scapular artery directly arose from the second part of the
      subclavian artery. In the period of 1989-1993, 6 rhombotrapezious island
      musculocutaneous flaps with vascularized pedicle were used for immediate repair
      in the skull base or craniomaxillary cancer operations. There was no complication
      of the flaps. Donor site complications were relatively minor. The disturbance in
      shoulder function was well tolerated. We advocated the incorporation of both the
      greater and lesser rhomboid muscle to form the compound rhombotrapezious flaps to
      enhance the vascular supply to the overlying skin. The major advantage of the
      RTIMF are that it provides a long paddle of thin pliant, hairless skin and muscle
      that can be rotated as far as the craniomaxilloface and scalp in a single stage.
      It offers the longest arc of rotation and thus the greatest versatility for the
      skull base or craniomaxillary reconstruction.

PMID- 7806202
TI  - [An uni-dimensional ordinal coma scale].
AB  - With the introduction and wide acceptance of the Glasgow coma scale, some
      progress was made in 1980s. Various types of coma scale were offered from
      different centers of the world for assessing coma and impaired consciousness. The
      existing coma scales may be divided into two main categories: (1) multi
      dimensional scale, e.g., Glasgow coma scale (GCS), Glasgow-Liege coma scale (G
      LCS), Maryland coma scale (MCS); and (2) uni-dimensional scale, e.g., Edinburgh-2
      coma scale (E2CS). There is evidence that the uni-dimensional coma scale is
      better than the multi-dimensional coma scale. The major drawbacks in the multi
      dimensional coma scale is the total figure of coma level must be envisaged
      stereographially. The sum of scores of three dimensions of GCS, as in a multi
      dimensional scale, consists of 13 levels from 3 through 15, but the numbers of
      simple combination constituting each score are considerable. No. 9 in GCS scale
      may be made up of 18 combinations. E2CS, as an uni-dimensional scale, seems to be
      an improvement over GCS. On the basis of comparison between two main categories
      of coma scale and considering the shortcomings of E2CS, a modified uni
      dimensional ordinal coma scale called "Chengdu-1 Coma scale" (C1CS) was proposed
      and applied for evaluating the depth of coma and for prognosticating the
      patients' outcome. This study was based on 98 acutely head-injured patients
      treated in the Neurosurgical department of 1st Affiliated Hospital of WCUMS, from
      October 1983 through May 1984. The follow-up results showed that a good
      correlation was observed between the score of C1CS and the outcome scale score
      (Glasgow outcome scale, GOS) of the patients.

PMID- 7806203
TI  - [Effects of phenytoin and cabamazepine on sex hormones in male patients with
      epilepsy: a controlled study].
AB  - We measured the levels of estradiol (E2), total testosterone (TT) and free
      testosterone (FT) in 24 male patients with epilepsy receiving phenytoin (DPH), 21
      male patients with epilepsy receiving cabamazepine (CBZ), 23 male epileptics
      receiving no treatment, and in 10 healthy age-matched male controls. The FT and
      TT levels of the DPH group were significantly lower and higher than those of the
      normal control group, respectively. The E2, FT and TT of the CBZ group were all
      lower than those of the normal controls. The results showed the difference
      between DPH and CBZ in the mechanism of affecting the levels of sex hormones;
      therefore, the treatments should not be the same.

PMID- 7806204
TI  - [Practical value of IgG index and IgG synthesis rate in multiple sclerosis].
AB  - IgG index and IgG synthesis rate were determined in 40 patients with multiple
      sclerosis (MS) (including 21 patients treated with corticosteroid), 20 patients
      with other neurological diseases (OND) and 22 normal controls, by Beckman
      Immunochemistry system II made in USA. The practical value of IgG index and IgG
      synthesis rate were evaluated by means of the method of clinical epidemiology.
      The results showed that in the diagnosis of MS the sensitivity, specificity and
      positive result likelihood ratio (PRLR) of IgG index were 63%, 65% and 1.80,
      respectively; those of IgG synthesis rate were 50%, 65% and 1.43, respectively.
      In the further observation, however, it was found that the sensitivity and PRLR
      were 84% and 2.4 in IgG index, 79% and 2.26 in IgG synthesis rate, after the
      influence of corticosteroid was excluded. In addition, in judging whether there
      was organic damage in central nervous system, the specificities and PRLRs of IgG
      index and IgG synthesis rate were 100% and infinitely great, respectively. The
      above results are discussed in this article.

PMID- 7806205
TI  - [CT diagnosis of primary cerebral lymphoma--report of 2 cases].
AB  - CT findings of 2 patients with primary cerebral lymphoma were presented with a
      literature review of the CT manifestations of primary cerebral lymphoma. On the
      plain CT scan, most of lymphomas were either hyper- or isodense, well demarcated,
      and had variable surrounding edema. The tumors were mostly situated in the deep
      structures of brain: the basal ganglia, corpus callosum, periventricular white
      matter and vermis of cerebellum. On the postcontrast CT scan, cerebral lymphomas
      showed a homogeneous contrast enhancement. Ring enhancement, occasionally gyral
      enhancement also may be seen. On the CT scan, primary cerebral lymphomas were
      usually misdiagnosed as glioma, meningioma, metastases and abscess. The
      difference between lymphoma and the above lesions was discussed.

PMID- 7806206
TI  - [Diagnosis of primary pulmonary hypertension--clinicopathologic analysis of three
      cases].
AB  - Three cases of primary pulmonary hypertension (PPH) were found in 6935 autopsies
      within the past 40 years at the university hospital. Comparative study of
      clinical and pathologic data were also performed. The authors reviewed the
      literature concerned, and discussed the diagnosis and misdiagnosis of PPH.

PMID- 7806207
TI  - [ELISA for measurement of human serum apolipoprotein A II].
AB  - A specific, sensitive and simple ELISA for the measurement of human serum apo A
      II has been developed. The monospecific antibody was raised in goats. The
      polytyrene plates coated with purified anti-apo A II goat gamma-globulin together
      with enzyme labelled goat antibodies against human apo A II conjugate were used
      in this assay. The conjugate was obtained by binding horseradish perioidate by a
      simplified periodase method. No cross-reactivity with human apo A I, B100, C I, C
      II, C III and albumin was observed. The minimum measurable concentration of apo A
      II was 500ng in each assay. A standard curve with a working range of 0.25-8.0
      mg/dl was plotted. The coefficients of variation of the reproducibility of intra-
      and interassays of apo A II in samples were 5.0-8.6% and 6.8-9.9% respectively.
      The recovery were 106.0 +/- 2.1% (n = 4). The mean concentrations of apo A II in
      41 healthy subjects were 24.4 +/- 5.9mg/dl by our method and 26.7 +/- 4.6 mg/dl
      by RID method, respectively (r = 0.8000, P < 0.001).

PMID- 7806208
TI  - [Determination of total arsenic in food by borohydride reduction colorimetric
      method].
AB  - A method for determination of total arsenic in food by borohydride reduction
      colorimetry is presented. After samples' digestion, the arsenic is converted into
      trivalent arsenic by KI-thiourea under heating when the solution's acidity is
      more than 1.0mol/L. Trivalent arsenic is then reduced by sodium borohydride to
      arsine gas which can react with AgNO3 in absorbing solution to form a yellow
      substance whose maximum absorption wavelength is 400nm. The method was applied to
      the determination of total arsenic in grape wine, carp, dried shrimp, rice powder
      and lettuce, and the variation coefficients were 13.3%, 12.8%, 8.2%, 12.2% and
      7.2%, respectively. The recoveries from dried shrimp, carp and rice powder were
      98.0%-112.0%, 82.0%-98.8%, and 84.2%-115.0%, respectively. The method was also
      applied to the determination of arsenic in reference material rice powder NBS
      1568 and the result, 0.37-0.43mg/kg, coincided with the given value 0.41 +/-
      0.05mg/kg.

PMID- 7806209
TI  - [Study of interaction between vitamin D2 and excipients by use of diffuse
      reflectance spectra].
AB  - The interaction of Vit D2 with calcium compounds and excipients commonly used was
      studied by use of diffuse reflectance spectra (DRS). The results indicated that
      there was some interaction between Vit D2 and calcium lactate, glucose, and a
      strong interaction between Vit D2 and magnesium stearate; and that the
      interaction between Vit D2 calcium gluconate, CaHPO4, sucrose, starch, lactose
      and mannitol was very weak and could even be neglected.

PMID- 7806210
TI  - Mapping and characterization of non-HLA multigene assemblages in the human MHC
      class I region.
AB  - The major histocompatibility complex (MHC) class I region has been shown to be
      associated with a variety of immune and nonimmune disorders. In an effort to
      initiate steps designed to identify the idiopathic hemochromatosis disease gene
      (HFE), we have cloned and mapped two expressed messages using probes from the HLA
      H subregion that lie immediately distal to the HLA-A9 breakpoint. Although the
      cDNA clones identify distinct multifragment families that are dispersed
      throughout the MHC, the gene sequences from which the two cDNA clones derive map
      centromeric to the HLA-B locus and are absent from the genomes of higher nonhuman
      primates. This suggests that a syntenic coding segment arose within a highly
      polymorphic region (TNF to HLA-B interval) as the result of an insertion event
      following the emergence of Homo sapiens. An additional syntenic cluster exists
      within a peak of linkage disequilibrium with the HFE gene and may define coding
      sequences that underlie the defect in genetic iron overload. These data generally
      support the concept that the class I region is potentially gene-rich and further
      highlight the possibility that these new coding sequences may play a role in the
      development of a variety of HLA-linked diseases. The observations presented
      suggest that interlocus exchanges have played a structural role in the genesis of
      the human class I region.

PMID- 7806211
TI  - Molecular cloning of the cDNA for human TrkC (NTRK3), chromosomal assignment, and
      evidence for a splice variant.
AB  - TrkC is a receptor tyrosine kinase that is activated by neurotrophin-3, a factor
      important in the development of certain areas of the central nervous system. We
      have cloned and sequenced the human trkC cDNA and found that the predicted amino
      acid sequence is 97 to 98% homologous to the rat and porcine trkC sequences,
      respectively. The rat trkC has several isoforms due to alternative splicing in
      the tyrosine kinase domain. We cloned one human splice variant that has a nucleic
      acid sequence identical to the rat isoform with an insert of 14 amino acids. The
      human trkC cDNA also has a (CGG)n repeat in the 5'-untranslated region. This
      sequence was not highly polymorphic in that 79 of 80 chromosomes examined had
      eight repeats, while 1 chromosome had four repeats. By PCR analysis of a somatic
      cell hybrid panel and fluorescence in situ hybridization with the cDNA clone,
      human trkC was mapped to chromosome 15q24-q25.

PMID- 7806212
TI  - Cloning of human microtubule-associated protein 1B and the identification of a
      related gene on chromosome 15.
AB  - We report here the complete cloning and sequencing of human microtubule
      associated protein 1B (MAP1B). Comparisons to mouse and partial rat MAP1B
      sequence indicate that this gene is extremely well conserved, with 91 and 90%
      identity, respectively. The entire human MAP1B genomic region has been isolated
      and the genomic organization determined. The gene includes seven exons, and the
      third exon contains sequence not represented in mouse or rat MAP1B. This
      sequence, labeled 3A, is present at the 5' end of an alternative transcript that
      is expressed at approximately 1/10th the level of the full-length transcript. By
      comparisons of human MAP1B with the sequence databases, we have identified a
      MAP1B-related gene that is probably the human homologue of rat MAP1A. This gene
      is expressed at high levels in brain and spinal cord and much lower levels in
      muscle and maps to the long arm of human chromosome 15.

PMID- 7806213
TI  - Chromosome locations of genes encoding human signal transduction adapter
      proteins, Nck (NCK), Shc (SHC1), and Grb2 (GRB2).
AB  - Abnormalities due to chromosomal aberration or point mutation in gene products of
      growth factor receptors or in ras gene products, which lie on the same signaling
      pathway, can cause disease in animals and humans. Thus, it can be important to
      determine chromosomal map positions of genes encoding "adapter" proteins, which
      are involved in transducing signals from receptor tyrosine kinases to downstream
      signal recipients such as ras, because adaptor protein genes could also,
      logically, serve as targets of mutation, rearrangement, or other aberration in
      disease. Therefore, DNAs from panels of rodent-human hybrids carrying defined
      complements of human chromosomes were assayed for the presence of the cognate
      genes for NCK, SHC, and GRB2, three SH2 or SH2/SH3 (Src homology 2 and 3) domain
      containing adapter proteins. Additionally, NCK and SHC genes were more narrowly
      localized by chromosomal in situ hybridization. The NCK locus is at chromosome
      region 3q21, a region involved in neoplasia-associated changes; the SHC cognate
      locus, SHC1, is at 1q21, and the GRB2 locus is at 17q22-qter telomeric to the
      HOXB and NGFR loci. Both SHC1 and GRB2 are in chromosome regions that may be
      duplicated in some tumor types.

PMID- 7806214
TI  - Population diversity and distinct haplotype frequencies associated with ACHE and
      BCHE genes of Israeli Jews from trans-Caucasian Georgia and from Europe.
AB  - Variant alleles of the butyrylcholinesterase gene, BCHE, have often been used to
      trace the genetic histories of populations. The D70G substitution in BCHE causes
      prolonged postanesthesia apnea ("atypical" phenotype); H322N substitution in the
      closely related acetylcholinesterase gene, ACHE, is the basis of the mutually
      incompatible Yt blood groups. In both genes, additional point mutations were
      reported to be linked to these phenotypically evident ones. To examine whether
      the intragenic linkage reported for the ACHE and BCHE mutations in Americans is
      universal, we studied frequencies of these mutations in trans-Caucasian Georgian
      Jews, a population that has remained relatively isolated for 1500 years. To this
      end we employed PCR amplification followed by DNA sequencing and enzymatic
      restriction and compared the frequencies we found to corresponding reported
      phenotype data. Georgian Jews' N322 ACHE was a rather low 7.0% and was totally
      linked to a P446 mutation, in agreement with a recent report. In BCHE, however,
      G70 was a relatively high 5.8%, and the V497 and T539 mutations were not found,
      either in Georgian or in Ashkenazi Jews, in contrast to reported findings in
      Americans. Our findings reveal distinct displays of ACHE and BCHE haplotypes in
      Georgian Jews and suggest different founder effects, genetic drifts, and/or
      selection pressures in the evolution of each of these genes.

PMID- 7806215
TI  - Refined mapping of a gene (NPH1) causing familial juvenile nephronophthisis and
      evidence for genetic heterogeneity.
AB  - Familial juvenile nephronophthisis (NPH) is an autosomal recessive progressive
      tubulo-interstitial kidney disorder, responsible for 6-10% of end-stage renal
      failure in children, and is frequently associated with Leber amaurosis (termed
      Senior-Loken syndrome). The biochemical basis of NPH is unknown. We recently
      reported linkage of the purely renal form of NPH to three markers on chromosome
      2. Our results also suggested the existence of genetic heterogeneity between NPH
      and SLS. To map this NPH gene more precisely, we have now tested the segregation
      of six new microsatellite markers and five additional families. Haplotype
      analyses show unequivocally that four NPH families are not linked to the
      chromosome 2 markers, although there are no clinical or pathological features
      discernible in these families that could separate them from the families linked
      to the chromosome 2 NPH locus (NPH1). This reveals genetic heterogeneity in the
      purely renal form of NPH. In situ hybridization of YAC clones isolated with two
      closely linked markers assigned the NPH1 region to 2q13. Furthermore, based on
      haplotype analysis and specific recombination events, the NPH1 gene has been
      placed between D2S293/D2S340 and D2S121, a genetic interval of about 5-7 cM.

PMID- 7806216
TI  - Mapping GRB2, a signal transduction gene in the human and the mouse.
AB  - We have mapped GRB2, a signal transduction gene whose protein product is an
      essential component of the pathway between tyrosine kinases (such as the
      epidermal growth factor receptor) and downstream proteins (such as Ras and Sos).
      We assigned GRB2 to human chromosome 17 by hybridization to a somatic cell hybrid
      mapping panel. To position the locus at a much finer resolution, we have isolated
      the human GRB2 gene in three different cosmids, which we have mapped by
      fluorescence in situ hybridization to the long arm of human chromosome 17 (17q24
      q25). We have hybridized a human GRB2 open reading frame probe to mouse DNAs from
      the European Interspecific Backcross. The segregation patterns reveal that the
      mouse Grb2 locus maps distally on chromosome 11, and an additional Grb2-related
      locus is present on chromosome 4 of one of the parental strains, Mus spretus/CRC.

PMID- 7806217
TI  - Multicolor FISH mapping of YAC clones in 3p14 and identification of a YAC
      spanning both FRA3B and the t(3;8) associated with hereditary renal cell
      carcinoma.
AB  - Human chromosome band 3p14 contains two tightly linked cytogenetic markers of
      broad interest, FRA3B and the t(3;8) breakpoint associated with hereditary renal
      cell carcinoma (RCC). The common fragile site at 3p14.2 (FRA3B) is the most
      sensitive site on normal human chromosomes to breakage when DNA replication is
      perturbed by aphidicolin or folate stress. The t(3;8)(p14.2;q24.1) translocation
      segregates with RCC in a large family and could mark the location of a tumor
      suppressor gene involved in renal cancers. In studies aimed at positional cloning
      of FRA3B and the t(3;8) breakpoint, we have used multicolor fluorescence in situ
      hybridization analysis (FISH) on metaphase spreads and interphase nuclei to order
      14 yeast artificial chromosomes (YACs) in 3p14. The YACs used in this study were
      identified by a group of unordered lambda clones that had been previously
      localized to the 3p14 region and mapped proximal or distal to the t(3;8)
      breakpoint. FISH analysis was used to order the YACs and to map them in relation
      both to the t(3;8) translocation breakpoint and to FRA3B induced on normal
      chromosomes by treatment with aphidicolin. YACs that closely flanked both the
      t(3;8) translocation breakpoint and the fragile site were identified. A YAC walk
      from the closest distal YAC allowed the identification of a 1.3-Mb YAC derived
      from the CEPH large insert YAC library that spans both the FRA3B and the t(3;8)
      breakpoint. The order of the YACs and cytogenetic landmarks in 3p14 is cen
      (126E1/230B9)-181H6-B15-D20F4-258B7-++ +280D2-70E12-168A8- 403B2-143C5-413C6
      468B10-[850A6/t(3;8)/ FRA3B]-74B2.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7806218
TI  - Strand asymmetry in human mitochondrial DNA mutations.
AB  - Replication of mitochondrial DNA is highly asymmetric between the heavy (H) and
      the light (L) strands. The parental H strand is displaced by the daughter H
      strand and remains in a single-stranded state until the daughter L strand is
      synthesized. To examine the effect of this asymmetric replication on mutagenesis,
      we determined sequences of mtDNAs from 43 human individuals. Occurrence of
      nucleotide substitutions at 4-fold degenerate sites was distinctly asymmetric
      between the two strands: G-->A and T-->C transitions were 9- and 1.8-fold more
      frequent on the L strand than on the H strand, respectively. This nucleotide
      substitution bias is consistent with the T and G abundance of the H strand as
      well as the A and C abundance of the L strand.

PMID- 7806219
TI  - Selection of chromosome 22-specific clones from human genomic BAC library using a
      chromosome-specific cosmid library pool.
AB  - A new approach to rapidly identify chromosome-specific subsets of clones from a
      total human genomic library is described. We report here the results of screening
      a human bacterial artificial chromosome (BAC) library using the total pool of
      clones from a chromosome 22-specific cosmid library as a composite probe. The
      human BAC library was gridded on filters at high density and hybridized with DNA
      from the pooled chromosome 22-specific Lawrist library under suppressive
      conditions. In a single hybridization, we picked 280 candidates from the BAC
      library representing over 30,000 clones (or 1.2x coverage of human genome). This
      subset contained more than 60% of the chromosome 22-specific BAC clones that were
      previously found to be present in the original BAC library. In principle, this
      approach can be applied to select a subset of clones from other global libraries
      with relatively large inserts using a pool from a regional library as a composite
      probe. It is important to note that the target and probe libraries must be based
      on vectors that share no homology with each other.

PMID- 7806221
TI  - Characterization of the PSG11 gene.
AB  - The pregnancy-specific beta 1-glycoproteins (PSG) form the major group of
      proteins synthesized in the human placenta. There are over 30 proteins in the
      family, encoded by 11 genes located on chromosomes 19q13.1-13.3. The genes can be
      divided into three subgroups based on the C-terminal exons expressed. The
      subgroup 1 genes have been well characterized. In this study the organization and
      sequence of a complete, functional, subgroup 3 gene is described. It contains the
      C-terminal exons, Cw, Cr, and Cs, which are expected from the transcripts
      characterized. Down-stream from these exons are sequences homologous to the C
      termini of the subgroup 1 type genes. This demonstrates that the subgroup 1, 2,
      and 3 genes are related via insertions/deletions. Comparison of the C-terminal
      sequences of the three subgroups of genes shows that the subgroup 2 and 3 genes
      are more closely related than, and are distinct from, the subgroup 1 genes.

PMID- 7806220
TI  - Genomic structure, promoter sequence, and revised translation of human homeobox
      gene HLX1.
AB  - The human homeobox gene HLX1 appears to be involved in hemopoietic development
      and may represent a candidate gene for various developmental or hemopoietic
      disorders. We have isolated genomic clones for the gene, determined its intron
      exon organization, and confirmed its map location on chromosome 1q41-q42. The
      transcription initiation sites of HLX1 were identified, and DNA sequences
      upstream of these sites were established. Finally, several differences between
      the genomic sequence and the published cDNA sequence were noted. Translation
      based on this revised sequence gives rise to a putative protein with 86.5%
      homology to the product of the murine Hlx gene.

PMID- 7806222
TI  - Complete coding sequence, deduced primary structure, chromosomal localization,
      and structural analysis of murine aggrecan.
AB  - We have isolated and sequenced overlapping cDNA clones encoding the entire core
      protein of aggrecan (the large aggregating chondroitin sulfate/keratan sulfate
      proteoglycan of cartilage) from three chondrocyte cDNA libraries of BALB/c mice
      and localized the aggrecan gene in mouse chromosome 7. We determined 7386 bp of
      the cDNA sequence, including 132 and 854 nucleotides of 5' and 3' untranslated
      regions, respectively. The core protein precursor is 2132 amino acids long (M(r)
      222,008), including a 19-residue secretory signal peptide. The overall amino acid
      sequence of the mouse aggrecan shows 91.6% identity to rat and 72.5% to human
      aggrecan. Comparison of the amino acid sequences of various domains and subdomain
      structures of mouse aggrecan to known sequences of other species and related
      proteins (versican, neurocan, link protein, and lymphocyte homing receptor CD44)
      revealed high levels of identity of the G1, G2, and G3 globular domains and
      relatively less conserved structures in the interglobular and glycosaminoglycan
      attachment regions. Epidermal growth factor (EGF)-like module was detected in
      only a minor fraction of aggrecan clones, while the complement regulatory protein
      (CRP)-like domain was regularly expressed in all samples.

PMID- 7806224
TI  - Mapping of the X-linked cataract (Xcat) mutation, the gene implicated in the
      Nance Horan syndrome, on the mouse X chromosome.
AB  - The Xcat mutation in the mouse, an X-linked inherited disorder, is characterized
      by the congenital onset of cataracts. The cataracts have morphologies similar to
      those of cataracts found in the human Nance Horan (X-linked cataract dental)
      syndrome, suggesting that Xcat is an animal model for Nance Horan. The Xcat
      mutation provides an opportunity to investigate, at the molecular level, the
      pathogenesis of cataract. As a first step to cloning the Xcat gene, we report the
      localization of the Xcat mutation with respect to known molecular markers on the
      mouse X chromosome. Back-cross progeny carrying the Xcat mutation were obtained
      from an interspecific cross. Genomic DNA from each mouse was subjected to
      Southern and PCR analysis to identify restriction fragment length polymorphisms
      and simple sequence length polymorphisms, respectively. Our results refine the
      location of Xcat to a 2-cM region, eliminate several genes from consideration as
      the Xcat mutation, identify molecular probes tightly linked with Xcat, and
      suggest candidate genes responsible for the Xcat phenotype.

PMID- 7806223
TI  - Isolation of a new gene GS2 (DXS1283E) from a CpG island between STS and KAL1 on
      Xp22.3.
AB  - A gene, GS2 (DXS1283E), was isolated from a CpG island located approximately
      midway between the steroid sulfatase (STS) and the Kallmann syndrome (KAL1) loci
      on the distal short arm of the human X chromosome. DNA sequencing of a GS2 cDNA
      clone revealed an open reading frame for a basic protein of 253 amino acid
      residues. A polymorphic CT dinucleotide repeat was found in the 3' untranslated
      region. The GS2 gene is expressed in all human tissues examined, including heart,
      brain, placenta, lung, liver, muscle, kidney, pancreas, and spleen. Several GS2
      transcripts, ranging in size from 1.1 to 5.8 kb, were found among different
      tissues, suggesting tissue-specific processing of the GS2 transcript.
      Characterization of GS2 genomic clones revealed that the gene consists of 7 exons
      spanning over 26 kb, with a CpG island located in the first intron. The GS2 gene
      is transcribed toward Xpter, in the same direction as KAL1 but opposite to that
      of STS.

PMID- 7806225
TI  - Genetic analysis of colon cancer susceptibility in mice.
AB  - Mouse models may aid in the identification of genes involved in colon cancer. Our
      mating scheme involved mouse strains selected for maximum differences in
      susceptibility to DMH-induced colon tumors. Tumors were found in 40 of 122
      progeny from a backcross to the resistant strain. We examined progeny animals for
      segregation of 177 genetic markers distributed at intervals of 5-30 cM on all
      mouse chromosomes. Multiple loci contribute to the phenotype, with significant
      linkage to a novel locus, Ccs1, between D12Mit5 and D12Mit6 on mouse Chr 12.
      Comparative maps suggest that the human homologue of Ccs1 is near FOS on human
      chromosome 14q.

PMID- 7806226
TI  - A YAC contig in 6p23 based on sequence tagged sites.
AB  - A yeast artificial chromosome (YAC) contig located in 6p23 and spanning roughly
      2.5 Mb has been constructed from the content of 10 sequence tagged sites (STSs)
      for YAC clones in 66 yeast colonies. Nine of the STSs have been genetically
      mapped in CEPH families. The order of STSs mapped with the contig is consistent
      with that of the genetic map. The order of loci that did not recombine with each
      other on the genetic map was inferred from the contig. Various regions of the
      contig are covered by multiple YAC clones that complement observed STS deletions.
      The STS for the CAG repeat sequence contained in the gene for spinal cerebellar
      ataxia 1 (gene symbol SCA1) is localized in the contig. It is likely that this
      gene is located in 6p23. The frequency of chimeric YAC clones in this contig is
      35%. Eleven yeast colonies were found to carry two or more YACs. YAC subclones
      from some of these colonies showed size variation, and for several subclones,
      evidence consistent with deletion of a sequence tagged site.

PMID- 7806227
TI  - Determination of evolutionary relationships among sheep breeds using
      microsatellites.
AB  - Eight ovine microsatellite loci were amplified in 40 to 50 unrelated individuals
      from six sheep populations representing five breeds: Romney, Border Leicester,
      Suffolk, Awassi, and both Australian and New Zealand Merino. For all of the
      microsatellite loci analyzed, there were highly significant differences in allele
      frequencies between samples from the different breeds. The allele frequencies
      generated can be used to determine the breed of an individual, given that it
      comes from one of the above breeds, to a high degree of accuracy. There were also
      some alleles that were found in only one breed, although these alleles were at
      such low frequencies that they are unlikely to be useful as markers for a breed.
      Genetic distances between breeds were obtained using Nei's formula to construct a
      phylogenetic tree. The tree grouped the Merino's in one branch and the Border
      Leicester, Suffolk, and Romney in another branch, while the Awassi, which was
      used as an outgroup, had its own branch. Using Nei's unbiased genetic distance
      formula to calculate the time of divergence of the British breeds from the Merino
      and the time of divergence between the Australian and the New Zealand Merino, we
      obtained t = 1094 and t = 227 years, respectively. Microsatellite genotyping in
      sheep appears to provide a useful tool for examining the evolutionary
      relationships between breeds.

PMID- 7806228
TI  - Physical mapping of the rat tissue kallikrein family in two gene clusters by
      analysis of P1 bacteriophage clones.
AB  - In several mammalian species the tissue kallikreins constitute gene families
      whose members encode a highly related subgroup of the simple serine proteases.
      Previous characterization of kallikrein genes in the rat identified 13 of the
      potential 15-20 members present in this species. To characterize comprehensively
      all members of the rat gene family and to define the linkage of family members,
      we have isolated clones bearing kallikrein genes from a rat genomic library
      constructed with the P1 bacteriophage vector pAd10-SacBII. Library pools
      containing kallikrein genes were identified by polymerase chain reaction with
      primers complementary to regions highly conserved among members of the rat gene
      family. Individual members of the family within the library pools were identified
      with gene-specific PCR assays that rely upon short divergent regions among the
      family members. Detection of multiple kallikrein family members within single
      library pools suggested tight linkage of the individual genes. Isolation and
      analysis of 12 kallikrein P1 clones confirmed the linkage of gene family members
      and established a physical map for two clusters of genes at the kallikrein locus.
      The linkage relationships of the known gene family members within the two gene
      contigs are rKLK1-rKLK3-rKLK7-rKLK9 and rKLK8-rKLK2-rKLK6-rKLK4-rKLK10-rKLK12++
      +. Pulsed-field electrophoretic analysis of rat genomic DNA demonstrated linkage
      between the two gene clusters, which form an extended locus that is most narrowly
      defined by a 440-kb BssHII fragment, and identified an unmethylated CpG island
      that is tightly linked to this locus.

PMID- 7806229
TI  - Two craniosynostotic syndrome loci, Crouzon and Jackson-Weiss, map to chromosome
      10q23-q26.
AB  - Crouzon syndrome (MIM 123500) is a common autosomal dominant form of
      craniosynostosis with shallow orbits, ocular proptosis, and maxillary hypoplasia.
      Jackson-Weiss syndrome (MIM 123150) is another autosomal dominant
      craniosynostosis with highly variable phenotypic expression. Unlike Crouzon
      syndrome, Jackson-Weiss syndrome is associated with foot anomalies. We performed
      two point linkage and haplotype analyses using 13 dinucleotide repeat markers on
      chromosome 10, spanning a genetic distance of 108 cM. The Crouzon syndrome locus
      (CFD1) maps to the region of chromosome 10q2, with the tightest linkage to locus
      D10S205 (Z = 3.09, theta = 0.00). the Jackson-Weiss syndrome locus in the large
      Amish pedigree in which the condition was originally described was also linked to
      the chromosome 10q23-q26 region between loci D10S190 and D10S186. The D10S209
      locus was most strongly linked (Z = 11.29, theta = 0.00).

PMID- 7806230
TI  - Fibulin-2 (FBLN2): human cDNA sequence, mRNA expression, and mapping of the gene
      on human and mouse chromosomes.
AB  - Fibulin-2 is a new extracellular matrix protein that we recently identified by
      characterizing mouse cDNA clones. Fibulin-2 mRNA is prominently expressed in
      mouse heart tissue and is present in low amounts in other tissues. In this study,
      we isolated and sequenced a 4.1-kb human fibulin-2 cDNA, which encoded a mature
      protein of 1157 amino acids preceded by a 27-residue signal sequence. The
      predicted polypeptide contains three consecutive anaphylatoxin-related segments
      (domain I) in its central region followed by 10 EGF-like repeats (domain II), 9
      of which have a consensus sequence for calcium binding. The 408-residue N
      terminal region consists of two separate subdomains, a cysteine-rich segment of
      150 residues (Na subdomain) and a cysteine-free segment with a stretch of acidic
      amino acids (Nb subdomain). The 115-residue C-terminal segment (domain III) is
      similar to the C variant of fibulin-1. The amino acid sequences of the human and
      mouse fibulin-2 share approximately 90% identity in domains Na, I, II, and III
      but only 62% identity in domain Nb. The human cDNA lacks an EGF-like repeat,
      which is alternatively spliced in the mouse cDNA clones, and a potential cell
      binding Arg-Gly-Asp sequence found in the Nb domain of the mouse counterpart.
      Northern blot analysis of mRNA from various human tissues reveals an abundant 4.5
      kb transcript in heart, placenta, and ovary tissue. The expression pattern
      differs from that of fibulin-1. The fibulin-2 gene was localized by in situ
      hybridization to the p24-p25 region of human chromosome 3 and to the band D-E of
      mouse chromosome 6.

PMID- 7806231
TI  - The fibulin-1 gene (FBLN1) is located on human chromosome 22 and on mouse
      chromosome 15.
AB  - Fibulin-1 is a calcium-binding glycoprotein present in the extracellular matrix
      and in the serum. The gene coding for fibulin-1 (FBLN1) was located by in situ
      hybridization of 3H-labeled cDNA probes to human and mouse metaphase chromosomes.
      The gene was assigned to the q13.2-q13.3 region of human chromosome 22 and to the
      E-F band of mouse chromosome 15. This finding extends the evolutionary
      conservation between human chromosome 22 and mouse chromosome 15.

PMID- 7806232
TI  - Regional localization of 725 human chromosome 7-specific yeast artificial
      chromosome clones.
AB  - Toward the construction of a complete physical map of human chromosome 7, we have
      localized 725 YAC clones to cytogenetically defined regions using fluorescence in
      situ hybridization (FISH) and by screening with DNA markers of known chromosomal
      locations. These chromosome 7-specific YAC clones are part of a library
      constructed with DNA isolated from monochromosomal 7 human-hamster somatic cell
      hybrid lines. The FISH mapping for 575 clones was accomplished by using "Alu-PCR"
      amplified YAC DNA against metaphase chromosome spreads made from a
      monochromosomal 7 human-mouse somatic cell hybrid line. Hybridization- or PCR
      based screening of previously mapped DNA markers was performed for the mapping of
      221 YAC clones. There was excellent correlation between the map locations
      obtained for the 71 YACs localized with both methods. All of the regionally
      localized YAC clones are valuable reagents for mapping and identification of
      disease genes on human chromosome 7.

PMID- 7806233
TI  - The gene Bfsp1 for the lens fiber cell beaded-filament structural protein CP94
      maps to mouse chromosome 2.
AB  - Bfsp1 is a mouse gene encoding the lens beaded-filament structural protein CP94.
      By use of rat CP94 cDNA as a probe, Southern hybridization of mouse DNAs prepared
      from the interspecific backcross progeny between Mus molossinus-mit and C57BL/6J
      strains was carried out. The results indicated that Bfsp1 maps at position 58 (+/
      6) on chromosome 2, in the vicinity of the blind-sterile (bs) locus.

PMID- 7806234
TI  - Physical mapping of the rat MHC class II genes shows a high level of interspecies
      conservation.
AB  - We report here a pulsed-field gel electrophoresis map of the rat major
      histocompatibility complex (MHC) class II region. Using probes for the recently
      discovered Tap-1 and Tap-2 genes and the different MHC class II genes, we found
      the gene order in the rat MHC (RT1) region to be RT1.H-Tap-1-Tap-2-Bb-Ba-Db-Da.
      Moreover, the distance between the Tap-1 and the RT1.Da genes is approximately
      150 kb. This, together with recent mapping of the RT1 class II region,
      demonstrates an extensive colinearity in the MHC region of different species.

PMID- 7806235
TI  - The structure of the human peripherin gene (PRPH) and identification of potential
      regulatory elements.
AB  - We determined the complete nucleotide sequence of the coding region of the human
      peripherin gene (PRPH), as well as 742 bp 5' to the cap site and 584 bp 3' to the
      stop codon, and compared its structure and sequence to the rat and mouse genes.
      The overall structure of 9 exons separated by 8 introns is conserved among these
      three mammalian species. The nucleotide sequences of the human peripherin gene
      exons were 90% identical to the rat gene sequences, and the predicted human
      peripherin protein differed from rat peripherin at only 18 of 475 amino acid
      residues. Comparison of the 5' flanking regions of the human peripherin gene and
      rodent genes revealed extensive areas of high homology. Additional conserved
      segments were found in introns 1 and 2. Within the 5' region, potential
      regulatory sequences, including a nerve growth factor negative regulatory
      element, a Hox protein binding site, and a heat shock element, were identified in
      all peripherin genes. The positional conservation of each element suggests that
      they may be important in the tissue-specific, developmental-specific, and injury
      specific expression of the peripherin gene.

PMID- 7806236
TI  - Chromosomal localization of four human VH1-like protein-tyrosine phosphatases.
AB  - Four human protein-tyrosine phosphatase (PTPase) genes of the VH1-like subclass
      were cloned by low-stringency screening of a genomic library. These genes were
      localized to their respective chromosomes by G-banding and fluorescence in situ
      hybridization. The genes were localized to unique regions of different
      chromosomes: CL100, a stress-induced PTPase, to 5q35; PAC-1, a mitogen-induced
      nuclear PTPase, to 2q11;hVH-3 to 10q25; and hVH-4 to 10q11.

PMID- 7806237
TI  - Genetic mapping of the Batten disease locus (CLN3) to the interval D16S288
      D16S383 by analysis of haplotypes and allelic association.
AB  - CLN3, the gene for juvenile-onset neuronal ceroid lipofuscinosis (JNCL) or Batten
      disease, has been localized by genetic linkage analysis to chromosome 16p between
      loci D16S297 and D16S57. We have now further refined the localization of CLN3 by
      haplotype analysis using two new microsatellite markers from loci D16S383 and SPN
      in the D16S297-D16S57 interval on a larger collaborative family resource
      consisting of 142 JNCL pedigrees. Crossover events in 3 maternal meioses define
      new flanking markers for CLN3 and localize the gene to the interval at 16p12.1
      p11.2 between D16S288 and D16S383, which corresponds to a genetic distance of 2.1
      cM. Within this interval 4 microsatellite loci are in strong linkage
      disequilibrium with CLN3, and extended haplotype analysis of the associated
      alleles indicates that CLN3 is in closest proximity to loci D16S299 and D16S298.

PMID- 7806238
TI  - A new human gene (DXS1357E) with ubiquitous expression, located in Xq28 adjacent
      to the adrenoleukodystrophy gene.
AB  - We have isolated a new human gene (DXS1357E; laboratory name: CDM) localized in
      Xq28. This gene is transcribed from the same CpG island as the
      adrenoleukodystrophy gene (ALD) and oriented in the opposite direction. It
      encodes a 1.5-kb transcript that exhibits ubiquitous expression and contains a
      single open reading frame. The 246 deduced amino acid sequence suggests the
      presence of membrane-associated segments and a weak similarity with the rod-like
      tail portion of heavy chain myosins from different species. The DXS1357E gene may
      be a candidate for one of the many diseases mapping to this region. A preliminary
      analysis did not show rearrangements of the gene in 19 independent patients with
      Emery-Dreifuss muscular dystrophy.

PMID- 7806239
TI  - Cloning and characterization of a 135- to 500-kb region of homology on the long
      arm of human chromosome 21.
AB  - The polymorphic marker D21S190 was initially isolated from a chromosome 21 phage
      library and mapped to two loci: one in 21q11.1 (proximal locus) and the other one
      in 21q22.1 (distal locus). To characterize the region of homology revealed with
      D21S190, we have screened two different chromosome 21 YAC libraries and one
      chromosome 21 cosmid library. Fluorescence in situ hybridization on normal human
      chromosomes of YACs, cosmids, and phages positive with D21S190 confirmed the
      existence of two homologous regions on the long arm of chromosome 21. Among the
      positive YACs, four (HY67, 2D7y21, 2D11y21, and 1B1y21) were selected and
      oriented relative to each other, forming a 2-Mb contig in the distal locus,
      including D21S54. Hybridization of YAC extremities to a panel of somatic cell
      hybrids containing various portions of chromosome 21 showed that the proximal
      locus is located between the breakpoints of 2Fu(r)1 and ACEM and the distal locus
      between the breakpoints of ACEM and 6918. The proximal and the distal breakpoints
      of JC6 are both included in the region of homology. We have constructed a
      restriction map of HY67, 2D7y21, and 2D11y21 spanning 1 Mb and including several
      markers: D21S294, D21S296, and the new STSs corresponding to YAC extremities. The
      region of homology encompasses 135-500 kb and has the same orientation in the
      distal and in the proximal locus, which are at least 12 Mb apart. It is lacking a
      NotI site but does contain clusters of GC-rich restriction sites, which are
      candidate regions for as yet unidentified genes.

PMID- 7806240
TI  - Human retinal guanylate cyclase (GUC2D) maps to chromosome 17p13.1.
AB  - 3',5'-Cyclic guanosine monophosphate is the intracellular second messenger
      regulating phototransduction in mammals. The level of cGMP in photoreceptor cells
      is controlled by the cGMP-hydrolyzing enzyme cGMP phosphodiesterase and the cGMP
      producing enzyme guanylate cyclase. Identification of a photoreceptor-specific
      guanylate cyclase (retGC) that may function in visual transduction was recently
      reported. As an initial step in assessing the potential for defects in the retGC
      (GUC2D) gene to be causal of hereditary retinal disease, we have determined its
      chromosome location. A 720-bp region of the human GUC2D locus was amplified with
      exon-specific primers. The amplified product contains three introns, two intact
      exons, and part of two additional exons, suggesting a high degree of structural
      complexity. PCR analysis of human-rodent somatic cell hybrids was used to map the
      GUC2D locus to chromosome 17. This assignment was confirmed and a more precise
      localization to 17p13.1 was obtained by fluorescence in situ hybridization.

PMID- 7806241
TI  - An algorithm to detect chimeric clones and random noise in genomic mapping.
AB  - Experimental noise and noncontiguous clone inserts can pose serious problems in
      reconstructing genomic maps from hybridization data. We describe an algorithm
      that easily identifies false positive signals and clones containing chimeric
      inserts/internal deletions. The algorithm "dechimerizes" clones, splitting them
      into independent contiguous components and cleaning the initial library into a
      more consistent data set for further ordering. The effectiveness of the algorithm
      is demonstrated on both simulated data and the real YAC map of the whole genome
      of the fission yeast Schizosaccharomyces pombe.

PMID- 7806242
TI  - An unusual mitochondrial DNA sequence variant from an Egyptian mummy.

PMID- 7806243
TI  - The ubiquitous subunit of the globin enhancer-binding protein NF-E2 (Nfe2u) maps
      to mouse chromosome 5.

PMID- 7806244
TI  - Localization of the glycine receptor alpha 1 subunit gene (GLRA1) to chromosome
      5q32 by FISH.

PMID- 7806245
TI  - Refinement of the localization of the gene for neuronal nicotinic acetylcholine
      receptor alpha 4 subunit (CHRNA4) to human chromosome 20q13.2-q13.3.

PMID- 7806246
TI  - Statistical methods in genetic mapping.

PMID- 7806247
TI  - In vitro activation of a nonproductive immunoglobulin allele by a single base
      pair insertion.
AB  - We have shown that one of the alleles in a hybridoma was nonproductive because
      the sequence in the N region of the heavy chain caused it to be out of frame and
      to terminate prematurely. This allele became productive, and the gamma 1 heavy
      chain that it encoded was secreted when an adenosine was inserted to produce an
      open reading frame. This event occurred at a very low frequency following
      mutagenesis of the cultured cells. This result suggests that similar sorts of
      events must occur in vivo when both productive and nonproductive alleles undergo
      frequent mutations and that new genes may be expressed in hybridomas as they are
      being subcloned.

PMID- 7806248
TI  - Production and characterization of monoclonal antibodies against guinea pig
      tracheal mucins.
AB  - Thirty-five hybridomas that secrete mouse monoclonal antibodies (MAb) against
      guinea pig (G.P.) tracheal mucins were established. The MAbs were characterized
      immunologically, biochemically, and immunohistochemically at both light and
      electron microscopic levels. Isotyping of the MAbs revealed 14 to be IgM, 13
      IgG1, 3 IgG2, and 5 IgG3. The MAbs demonstrated various patterns of binding in
      immunoblots against mucins derived from G.P. tracheal explants. This suggested
      the presence of "subpopulations" of G.P. tracheal mucins with specific MAbs
      binding to different epitopes on the mucin molecules. Periodate oxidation
      indicated that 33 of the 35 MAbs recognized carbohydrate epitopes on the mucin
      molecules. Ten of the MAbs also reacted with both bovine and ferret tracheal
      mucins, while 7 and 6 MAbs bound only to bovine and ferret tracheal mucins,
      respectively. The generated MAbs should be useful for immunomeasurement of mucin
      secretion in vivo (e.g., in bronchoalveolar or airway lavage fluid) and in vitro
      (e.g., cell and organ cultures) from cells of guinea pig and (with certain MAbs)
      bovine and ferret origin.

PMID- 7806249
TI  - Generation of monoclonal antibodies to the anti-trypanosomal drug isometamidium.
AB  - Mice were immunized with either an isometamidium-human serum albumin (HSA)
      conjugate or an isometamidium-porcine thyroglobulin conjugate (PTG). Thereafter,
      monoclonal antibodies (MAbs) IL-A 1001, IL-A 1002, IL-A 1003, 5F7.B7, and 5F7.C9
      were generated and selected on the basis that they recognized conjugated and
      unconjugated isometamidium, but lacked cross-reactivity with the carrier
      molecules. All five MAbs were of the IgG1 isotype. Each of the five MAbs was
      assessed in a competitive ELISA for isometamidium; in each case, the minimum
      level of detection was approximately 10 ng/ml. Each MAb exhibited approximately
      0.1% cross-reactivity with the anti-trypanosomal compound diminazene. However,
      based on their cross-reactivity with the anti-trypanosomal compound homidium, the
      MAbs could be divided into two groups; IL-A 1001, IL-A 1002, and IL-A 1003,
      produced using an isometamidium-HSA conjugate as an immunogen, exhibited low
      levels of cross-reactivity (approximately 0.1%). In contrast, 5F7.B7 and 5F7.C9,
      produced using an isometamidium-PTG conjugate as an immunogen, exhibited high
      levels of cross-reactivity.

PMID- 7806250
TI  - Monoclonal antibodies directed to the synthetic carbohydrate antigen Ley.
AB  - Tetrasaccharide Fuc alpha 1-2Gal beta 1-4(Fuc alpha 1-3)GlcNAc is known as
      carbohydrate determinant of cancer- and AIDS-associated antigen Lewisy (Ley).
      Synthetic antigen to generate mouse monoclonal antibodies (MAbs) directed to Ley
      was prepared and constructed as a spacer-armed tetrasaccharide coupled with
      lipophilized polymer, Ley-PAA-PE, where PAA is a 30-kD polyacrylamide and PE is
      phosphatidylethanolamine. An efficient immune response was provided by using Ley
      PAA-PE adsorbed on Salmonella minnesota. Positive hybridomas were screened by
      enzyme-linked immunosorbent assay (ELISA) using Ley-PAA as a coating agent. An
      inhibitory version of the same test system showed absolute specificity of two
      MAbs: only hapten Ley and Ley-PAA were strong inhibitors, in contrast to Leb, tri
      and disaccharidic fragments of the mentioned tetrasaccharides, as well as their
      PAA-conjugates. MAbs obtained against synthetic antigen specifically stained the
      Ley (+) cell line A431.

PMID- 7806251
TI  - Development of anti-human B blood group monoclonal antibodies suitable as a blood
      typing reagent.
AB  - An improved procedure for the generation of high-avidity anti-human B blood group
      monoclonal antibodies (MAbs) was developed. One of them, termed 7A1-2, showed
      excellent qualities of titer, avidity, and intensity required for use as human B
      blood typing reagent. Hemagglutination inhibition studies with monosaccharides
      and oligosaccharides were carried out to determine the specificity of the MAb 7A1
      2. These studies indicate that the antibody reacts with the immunodominant region
      of the antigen which is known to confer the serologic specificity of this blood
      group.

PMID- 7806252
TI  - Monoclonal antibodies recognizing 2-oxo acid dehydrogenase components in granular
      structures in neurons.
AB  - Monoclonal antibodies (MAbs) were raised against the hippocampal homogenate of
      young rats and classified into three types by immunohistochemical analysis: (1)
      MAbs specific for a granular structure observed within neurons, (2) MAbs specific
      for neuronal cell surface and cell body, and (3) MAbs specific for both neurons
      and astroglial cells. One MAb (2D11-7) specifically reacted with granular
      structures observed in neurons. A specific protein antigen was purified from rat
      homogenate by immunoadsorbent assay with MAb 2D11-7. Amino acid sequencing
      followed by lysyl endopeptidase digestion of the proteins in the eluate
      demonstrated that the antigens recognized by MAb 2D11-7 were E2 components of the
      2-oxoglutarate dehydrogenase complex and pyruvate dehydrogenase complex. The cell
      specificity and age dependency of these proteins are also discussed.

PMID- 7806253
TI  - Characterization and regional binding of human sperm monoclonal antibodies.
AB  - Five monoclonal antibodies (MAb) with specific binding for tail, midpiece,
      equatorial region, and postacrosome of human sperm were selected. The reactivity
      of the MAbs was tested by three techniques: an ELISA with human sperm, an
      indirect immunostaining analyzed by a cell sorter, and immunofluorescence on the
      cell where the antigens were localized. The localization or exposure of the
      antigens changes throughout the in vitro capacitation. These antigens are
      distributed among other mammalian species: mouse, ram, and goat. Their presence
      was also analyzed in some human tissues: peripheral blood mononuclear cells,
      spleen, pancreas, thyroid, heart, skin, intestine, and lung. No cross-reactivity
      was detected. Some of the MAbs showing tail staining severely inhibited sperm
      motility after 5 hr of incubation with sperm, although no agglutination was
      present. This immobilizing activity of MAbs would prevent spermatozoa from
      reaching the oocyte in vivo.

PMID- 7806254
TI  - Monoclonal antibodies reacting with the mucin-specific lectin from Sambucus
      sieboldiana (SSA-M).
AB  - Monoclonal antibodies (MAbs) were prepared against the mucin-specific lectin from
      Sambucus sieboldiana (SSA-M). The majority of MAbs reacted with both free SSA-M
      and SSA-M bound to porcine mucin. However, MAbs SS16, SS18, and SS19 did not
      react with mucin-bound lectin, suggesting that these MAbs may react at or near
      the lectin binding site. Some MAbs also showed reactivity with lectins other than
      SSA-M (e.g. ConA, Pisum sativum, and Saphora japonica lectins) suggesting
      possible sequence homology between SSA-M and other lectins. These MAbs should be
      useful reagents for immunoaffinity purification of SSA-M, characterizing SSA-M
      structure and binding, and metabolic studies on mucins.

PMID- 7806255
TI  - Immortalization of human primary B lymphocytes by simian virus 40 early region
      DNA.
AB  - We obtained several immortalized human primary B-lymphocyte cultures by
      transfection of the plasmid DNA, which consisted of simian virus 40 early-region
      DNA (pSVTbsr). These immortalized B lymphocytes grew in a suspension culture
      forming cell clumps, expressed CD23, and had an interleukin-6 (IL-6)
      susceptibility for immunoglobulin (Ig) production, although there was an absence
      of Epstein-Barr nuclear antigen. Therefore, the action of introduced pSVTbsr is
      equivalent to the Epstein-Barr virus infection through induction and maintenance
      of immortalized state of the primary B lymphocytes.

PMID- 7806256
TI  - FACS analysis of peritoneal lymphocytes in ovarian cancer and control patients.
AB  - In this study different lymphocyte populations in the malignant ascites of 10
      patients with ovarian carcinoma and in the peritoneal fluid of 8 control patients
      (tubal ligation and benign conditions) were analyzed. A panel of monoclonal
      antibodies against the CD markers of lymphocytes was used to stain different
      populations and the cells were analyzed on a FACS II (fluorescence-activated cell
      sorter). The mean percentage of B lymphocytes in the peritoneal cavity of the
      OVCA patients was 0.18 +/- 0.5% and in the control patients 0.05 +/- 0.07%. There
      was no significant difference between the two groups. In the OVCA group and in
      the controls the percentage of T lymphocytes (CD5+) was 23.5% and 17.1%
      respectively with no significant difference between the groups. These results
      indicate that B lymphocytes are not present in the human peritoneal cavity. The
      small numbers of B cells found in this study could be due to contamination with
      peripheral blood. The human peritoneal cavity contains a cell population which
      differs from that present in peripheral blood. Significant numbers of B
      lymphocytes have been reported in the peritoneal cavity of mice. The difference
      between the lymphocyte population of the human peritoneal cavity and that of
      rodents implies that data on characterization and function of B lymphocytes in
      the mouse peritoneal cavity would not be applicable to humans.

PMID- 7806257
TI  - Effects of interleukin-6 on hematopoiesis in allogeneic and syngeneic bone marrow
      chimeras.
AB  - Effects of interleukin-6 (IL-6) on hematopoietic progenitor cells were analyzed
      in murine bone marrow chimeras. When IL-6 was injected into syngeneic [C3H/He-
      >C3H/He] bone marrow chimeras from day 1 to day 12, the numbers of highly
      proliferative potential colony-forming units (CFU-HPP) or colony-forming units
      mix (CFU-Mix) in spleen cells and bone marrow cells increased on day 14 although
      there was a marked increase in spleen cells but not in bone marrow cells on day
      21. The numbers of CFU-HPP increased in spleen cells from allogeneic [BALB/c-
      >C3H/He] bone marrow chimeras injected with IL-6 on days 14 and 21. In syngeneic
      bone marrow chimeras, the numbers of colony-forming units granulocyte/macrophage
      (CFU-GM) and burst colony-forming units (BFU-E) increased similarly to those of
      CFU-HPP and CFU-Mix on day 14. On day 21, these were mainly increased in spleen
      cells. In allogeneic bone marrow chimeras, IL-6 decreased the numbers of CFU-GM
      and BFU-Mix dose-dependently on day 14. Only 10 micrograms of IL-6 increased the
      numbers of CFU-GM and BFU-E on day 21. In our previous work, we showed that
      platelet counts increased on day 14 in syngeneic bone marrow chimeras injected
      with IL-6, whereas platelet and leukocyte counts increased on days 14 and 24 in
      allogeneic bone marrow chimeras injected with IL-6, correlating inversely with
      the numbers of hematopoietic progenitor cells. Overall, primitive hematopoietic
      progenitors (i.e., CFU-HPP and CFU-Mix) existed primarily in spleen cells of
      allogeneic bone marrow chimeras on day 14, whereas those in spleen cells of
      syngeneic bone marrow chimeras were found on day 21. These findings indicate that
      the effect of IL-6 on hematopoiesis in allogeneic bone marrow chimeras is
      completely different from that in syngeneic bone marrow chimeras, probably via
      graft-versus-host reaction (GVHR) but not GVH disease (GVHD).

PMID- 7806258
TI  - Macrophage subpopulations in the mouse spleen renewed by local proliferation.
AB  - A dual origin, by both immigration of blood monocytes and local proliferation has
      been reported for macrophages, which are heterogeneous in several aspects. Until
      now few studies have focussed on renewal of macrophages. Therefore, in this study
      macrophage renewal by local proliferation has been studied in the spleen. Spleen
      tissue of mice which had received BrdU intravenously was investigated
      immunohistochemically to detect BrdU incorporated by macrophages. BrdU
      incorporation by splenic macrophages was studied under steady state conditions as
      well as during repopulation after experimental macrophage depletion. Under steady
      state conditions, BrdU incorporation was found in 3.0 +/- 0.5% of the white pulp
      macrophages and in approximately 1% of the metallophilic macrophages only.
      Comparable results were found during repopulation after experimental macrophage
      depletion. The data suggest that renewal of macrophages by local proliferation is
      restricted to certain subsets in the spleen and that the macrophage subsets of
      the spleen are renewed by different mechanisms, or belong to different lineages
      of macrophage differentiation.

PMID- 7806259
TI  - Lowered expression of C3b receptor (CR1) on erythrocytes of rheumatoid arthritis
      patients.
AB  - The number of C3b receptors (CR1) on erythrocytes (E) has been quantitated by
      whole cell enzyme-linked immunosorbent assay (ELISA), using a monoclonal anti-CR1
      antibody, in 46 healthy individuals as controls, 58 having rheumatoid arthritis
      (RA) and 3 hereditary angioedema patients. The mean value of CR1 in RA (381/E)
      was significantly lower (p < 0.001) when compared to normal controls (646/E). In
      hereditary angioedema patients CR1 numbers (620/E) were found to be comparable to
      normal values. No significant difference was found between normal male (708/E)
      and female (598/E) subjects. Among the patient groups, those on steroid therapy
      (352/E) showed no change compared to others not receiving such therapy (408/E).
      The cumulative frequency curve of CR1 in the normal population showed maximum
      inflection at 32% and 82%. This led us to conclude that there is a trimodal
      distribution of receptors in the control population. Such a contention is well
      supported by frequency histogram, when a small group interval (0-50) was chosen.
      However, if large group intervals (0-100 or 0-150) were considered, a very close
      approximation to unimodal pattern was obtained. The factors actually contributing
      to low receptor numbers are yet to be elucidated.

PMID- 7806260
TI  - Single-chain antibody variable region-targeted interleukin-2 stimulates T cell
      killing of human colorectal carcinoma cells.
AB  - Recombinant DNA techniques were used to clone, construct and express the
      bifunctional molecule FV/IL-2. The FV/IL-2 is a single-chain 37 kDa fusion
      protein expressed in Escherichia coli under control of the strong T7
      bacteriophage promoter in the expression vector pT7-7-FV-IL-2. The fused gene
      fragment FV-IL-2 contains a single-chain anti-TAG72 FV gene fragment and the
      human recombinant cDNA fragment of the IL-2 molecule. The renatured soluble form
      of FV/IL-2 was purified from E. coli inclusion bodies using hydroxylapatite
      chromatography. The yield of this fusion protein was estimated at 2.0 mg/L. Our
      data showed that the FV/IL-2 molecule retained the TAG72 antigen-binding
      specificity and the IL-2 activity as measured in the standard T cell
      proliferation as well as cytotoxicity assays. Therefore, it may prove to be
      useful in targeting the biological effect of IL-2 to tumour cells and stimulating
      its immune destruction.

PMID- 7806261
TI  - Plasmodium falciparum and blood monocyte induced abnormalities in human
      erythrocyte cation homeostasis.
AB  - The role of Plasmodium falciparum and activated blood monocytes in bringing about
      erythrocyte membrane lipid peroxidation and in altering the enzyme activity
      associated with Ca2+ and K+ efflux was studied. An attempt was made to
      investigate the role of parasite and monocyte-mediated reactive oxygen species
      (ROS) in inhibiting Ca(2+)-Mg2+ ATPase and Na(+)-K+ ATPase in order to find out
      the cause of reported high intra-erythrocytic calcium and depleted potassium
      levels in parasitized erythrocytes (PRBC). The PRBC showed enhanced lipid
      peroxidation as indicated by increased malonyldialdehyde (MDA) formation which
      coincided with the maturity of the parasite. This was further enhanced following
      exposure of PRBC to activated blood monocytes. The Ca(2+)-Mg2+ ATPase activity
      was decreased as the parasite matured and was further hampered significantly in
      mature parasite-infected red cells exposed to activated blood monocytes. There
      was a good negative correlation between MDA formation and Ca(2+)-efflux from red
      blood cells suggesting the negative influence of ROS on Ca(2+)-efflux. The Na(+)
      K+ ATPase activity did not reveal any significant change, both during parasite
      maturation as well as upon exposure to ROS from activated monocytes. We therefore
      suggest that inhibition of Ca(2+)-efflux and the resulting increased cytosolic
      Ca2+ in PRBC might have a role in structural and functional abnormalities of red
      blood cell, thus enhancing the red cell loss during P. falciparum infection.

PMID- 7806262
TI  - Differential modulation of human multinegative (CD3-4-8-) thymocyte proliferation
      by monoclonal antibodies to CD45RA or to CD45.
AB  - Human multinegative (CD3-4-8-19-; MN) thymocytes proliferate optimally in
      response to anti-CD2 plus anti-CD28 mAb plus PMA or IL-7. The role of CD45 was
      assessed by the addition of mAb to a CD45 common determinant, or to CD45RA. MN
      thymocytes are unresponsive to anti-CD2 mAb. Co-stimulation with anti-CD45RA
      generated 1.6-5.7-fold enhancement of a proliferative response, with maximal
      enhancement by cross-linkage of CD45RA molecules. The response to anti-CD2/28 mAb
      was reproducibly enhanced only by immobilized anti-CD45RA. Cross-linking of
      CD45RA and CD28 through the use of heteroconjugates of mAb did not enhance the co
      stimulation by CD45RA. The most marked enhancement by anti-CD45RA occurred in
      suboptimal activation conditions. In contrast, the response to anti-CD2 or anti
      CD2/28 was inhibited by mAb to CD45 common determinants (anti-CD45) in the
      presence or absence of PMA or IL-7, with the most profound inhibition (6-8-fold)
      detected in optimal proliferative conditions. Cross-linking of CD45 and CD28
      through heteroconjugates of mAb was required as soluble anti-CD45 or immobilized
      anti-CD45 were unable to mediate inhibition. This inhibitory effect of (anti-CD45
      x 28) was specific to MN thymocytes as no inhibition was detectable when
      peripheral blood T cells were treated with anti-CD2/28 and the same
      heteroconjugate. The differential effects of anti-CD45 and anti-CD45RA may
      reflect either CD45 heterogeneity on MN thymocytes, or the physical modulation of
      a single CD45 molecules by interactions at different epitopes, and the avidity of
      the relevant CD45 mAb for thymocyte CD45 isoforms may play a role.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7806263
TI  - Role of insulin-like growth factor-1 on the kinetics of human lymphocytes
      stimulation in serum-free culture medium.
AB  - In a serum-free medium addition of insulin-like growth factor-1 (IGF-1)
      consistently enhanced lymphocyte proliferation response to PHA in a dose
      dependent fashion. This effect was produced by an acceleration in the expression
      of clone expansion and not in the number of proliferating cells. This was
      documented by kinetics data obtained from the first proliferation round of PHA
      stimulated lymphocytes, in which addition of IGF-1 reduced G1-phase length,
      without changing G0-phase, S-phase or cloned size. The data were confirmed in 10
      day culture of stimulated lymphocytes where IGF-1 only accelerated cell
      proliferation without modifying the area enclosed by the proliferation curve. As
      IGF-1 is under the control of growth hormone, our results suggest that some of
      the immuno-regulation effects ascribed to growth hormone in vivo could be
      produced by IGF-1.

PMID- 7806264
TI  - Phenotype of T cells, their soluble receptor levels, and cytokine profile of
      human breast milk.
AB  - Human breast milk has important immunoprotective and immunosuppressive functions
      for an infant. The purpose of this study was to extend the phenotype of milk
      cells and to measure soluble T cell receptor levels and cytokines in milk, and to
      compare these with neonatal and adult blood. Milk T cells had a more equivalent
      CD4:CD8 ratio than blood; milk CD4 T cells mainly expressed the CD45RO (antigen
      primed/memory) phenotype; milk CD8 cells had an equivalent CD11b:CD28
      suppressor:cytotoxic phenotype; and milk T cells had 2-3-fold higher percentages
      of activated CD4 IL-2R and CD8 HML-1 or CD8 VLA-1 cells than blood. Soluble IL
      2R, CD4 and CD8 concentrations were lower in milk than adult blood, although
      relatively increased when compared to the lower T cell concentration in milk.
      Breast milk contained high levels of IFN-gamma but low levels of other measured
      cytokines compared to blood. These distinct differences of T cells and their
      soluble products are likely to influence an infant's immune system.

PMID- 7806265
TI  - Measurement of cellular microbicidal activity against Pneumocystis carinii in
      vitro.
AB  - As Pneumocystis carinii cysts cannot be cultivated for enumeration of colony
      forming cells, two alternative approaches to measuring killing of P. carinii by
      mouse peritoneal cells were investigated. The cells tested were either normal
      resident peritoneal cells, or cells which were elicited by intraperitoneal
      injection of the bacterium Listeria monocytogenes. The latter population showed
      enhanced antibacterial activity against Listeria organisms and enhanced
      production of H2O2 in the presence of P. carinii, cysts from immunosuppressed
      rats. To assess killing of P. carinii, cysts were mixed with peritoneal cells at
      a ratio of 10:1, and after intervals of incubation the peritoneal cells were
      lysed by saponin treatment. The viability of the cysts was assessed by staining
      with vital dyes or by uptake of tritiated uridine over 7 h incubation. Viability
      of cysts was unaffected by saponin treatment, and there was agreement between the
      two techniques that the elicited peritoneal cells killed approximately twice the
      number of cysts over a 20 h incubation period compared to normal resident
      peritoneal cells.

PMID- 7806266
TI  - A cell-surface opsonic receptor on leucocytes from the phylogenetically primitive
      vertebrate, Eptatretus stouti.
AB  - A humoral recognition molecule that is homologous to the mammalian complement
      components C3, C4 and C5 has recently been identified in the Pacific hagfish,
      Eptatretus stouti. One function of this complement-like protein (CLP) is to
      opsonize foreign material for phagocytosis by hagfish leucocytes. Here, we
      demonstrate that CLP's opsonic activity can be abrogated by pre-incubating
      phagocytes with an anti-hagfish leucocyte mAb (1B1). Moreover, antigen-activated
      CLP can block the binding of the 1B1 antibody to hagfish leucocytes. Flow
      cytometry and immunoprecipitation indicate that 1B1 recognizes a 105 kDa cell
      surface, monomeric protein that is expressed exclusively on phagocytic hagfish
      leucocytes. It is concluded that this 105 kDa protein represents the cell surface
      receptor by which CLP mediates the phagocytosis of opsonized targets.

PMID- 7806267
TI  - An association between successful vaccination against the bovine nodular worm,
      Oesophagostomum radiatum and induction of eosinophilia.
AB  - Immunization of 48 cattle with somatic antigen extracts of the nodular worm,
      Oesophagostomum radiatum, reduced faecal egg counts (FEC) by 51% and worm burden
      by 47%. The antibody titre of each animal was correlated to both worm burden (r =
      -0.40, P < 0.005) and FEC (r = -0.37, P < 0.01). The vaccinated cattle showed
      wide variation in their response to vaccination with worm burdens after challenge
      infection varying from 0 to 4060. Of these 48 vaccinated animals, eight developed
      sterile immunity (worm burden = 0, FEC = 0) whereas a further 10 had no
      protective response to immunization (worm burden > 1,000, FEC > 100). A
      comparison of these two sub-groups showed that the group with sterile immunity
      had a higher antibody titre (P < 0.05). In addition, the group with sterile
      immunity developed a blood eosinophilia between 21 and 29 days after challenge
      infection. Vaccinated, unprotected calves and control, unvaccinated calves did
      not develop eosinophilia.

PMID- 7806268
TI  - Co-selection in immune network theory and in AIDS pathogenesis.
AB  - Co-selection is a term used to denote the mutual positive selection of individual
      members from within two diverse populations, such that selection of members
      within one population is dependent on interaction with (recognition of) one or
      more member(s) within the other population. Co-selection is a recurring theme of
      the idiotypic network model that my colleagues and I have developed. This paper
      discusses the role that co-selection plays in basic symmetrical network theory
      and in a network model that resolves the I-J paradox. It proposes that co
      selection of helper T cells and HIV variants plays a role in the pathogenesis of
      AIDS. The AIDS model involves a role for the T cell receptor in the infection of
      T cells. Finally, a way in which a co-selection process may potentially be used
      in the prevention and therapy of harmful forms of immunity is described.

PMID- 7806270
TI  - Evolution of immunoglobulin heavy chain variable region genes: a VH family can
      last for 150-200 million years or longer.
AB  - Many immunoglobulin variable region (IgV) genes are present in the vertebrate
      genome and provide a basis for antibody diversity. IgV genes have been classified
      into distinct families according to DNA sequence similarity. Comparisons of VH
      and VL genes from two mammalian species (mouse and human) have led to the
      conclusion that some V gene families are stable over 65 million years of
      evolution. Here we show that a VH family can be stable for 150-200 million years
      or longer. This conclusion is drawn from our extensive comparison of VH genes
      between two species of low vertebrates (rainbow trout and catfish), and from the
      estimation of species divergence time by the substitution rate of an IgM constant
      domain. The estimated speed of VH gene evolution explains the moderate degree of
      sequence similarity in VH gene families between a mammal (mouse) and a teleost
      (rainbow trout). The distribution of species-specific amino acid residues in
      certain VH families indicates that the process of sequence homogenization plays a
      major role in shaping the V gene family.

PMID- 7806269
TI  - "Both man & bird & beast": comparative organization of MHC genes.

PMID- 7806272
TI  - The Asp116-His116 substitution in a novel HLA-B27 subtype influences the
      acceptance of the peptide C-terminal anchor.

PMID- 7806271
TI  - Allelic diversity at the Mhc-DP locus in rhesus macaques (Macaca mulatta).
AB  - Allelic diversity at the major histocompatibility complex class II DP locus of
      rhesus macaques was studied by sequencing exon 2 of Mamu-DPA1 and -DPB1 genes.
      The Mamu-DPA1 gene is apparently invariant, whereas the Mamu-DPB1 locus displays
      polymorphism. Here we report the characterization of 1 Mamu-DPA1 and 13 Mamu-DPB1
      alleles which were compared with other available primate Mhc-DPA1 and -DPB1
      sequences. As compared with Mhc-DRB and -DQB1, most codons for the contact
      residues in the antigen binding site of the primate Mhc-DPB1 gene have a
      relatively low degree of variation in encoding various types of amino acids. In
      contrast to Mhc-DRB and -DQB, the HLA- and Mamu-DPB1 sequences cluster in a
      species-specific manner in phylogenetic trees. Mhc-DPB1 polymorphisms, however,
      are inherited in a transspecies mode of evolution, as is demonstrated by the
      sharing of lineage members between closely related macaque species. The data
      demonstrate that the transspecies character of Mhc-DPB1 polymorphism was retained
      over much shorter periods of time as compared with its sister class II loci, Mhc
      DQ and -DR.

PMID- 7806273
TI  - The closely linked genes encoding the myeloid nuclear differentiation antigen
      (MNDA) and IFI16 exhibit contrasting haemopoietic expression.

PMID- 7806275
TI  - The natural killer cell serine protease gene Lmet1 maps to mouse chromosome 10.

PMID- 7806274
TI  - Genetic mapping of the LMP2 proteasome subunit gene to the BoLA class IIb region.

PMID- 7806276
TI  - Characterization of a novel HLA-A2 variant, A*0214, by ARMS-PCR and DNA
      sequencing.

PMID- 7806277
TI  - Exon 2, 3, and 4 polymorphism of HLA-DPA1.

PMID- 7806278
TI  - Recombination activating gene 1 (Rag1) in zebrafish and shark.

PMID- 7806279
TI  - Nucleotide sequence of a novel HLA-DRB1 allele, DRB1*0806.

PMID- 7806280
TI  - An alternatively spliced interleukin 4 form in lymphoid cells.

PMID- 7806281
TI  - A susceptibility gene for alveolar lung tumors in the mouse maps between Hsp70.3
      and G7 within the H2 complex.
AB  - Lung tumor susceptibility (LTS) in the mouse is influenced by multiple loci
      within the H2 complex. We compared the LTS of two H2 congenic strains with intra
      H2 recombinations, B10.A(1R) and B10.A(2R), whose genetic difference has been
      reduced to a region of approximately 50 kilobases within the C4-H2D interval,
      between Hsp70.3 and G7. After transplacental induction with N-ethyl-N-nitrosourea
      the load of alveolar lung tumors in strain B10.A(2R) is significantly higher than
      in strain B10.A(1R) (P < 0.001). For papillary tumors no significant differences
      were observed. We conclude that the alveolar lung tumor load is influenced by an
      LTS gene located within the Hsp70.3-G7 interval.

PMID- 7806282
TI  - An alternative way of CD4 and CD8 association with protein kinases of the Src
      family.
AB  - The T-lymphocyte co-receptors of MHC glycoproteins CD4 and CD8 are known to be
      associated with the protein tyrosine kinase Lck via cysteine-containing sequences
      in the cytoplasmic domains of CD4 and CD8 and in the N-terminal domain of Lck.
      Here we demonstrate that a fraction of CD4 and CD8 molecules are associated with
      very large, detergent-resistant complexes containing several
      glycosylphosphatidylinositol-anchored proteins, (glyco)lipids, and protein
      tyrosine kinases Lck and Fyn but apparently no other major transmembrane
      proteins. Association of Lck and Fyn with these large complexes is, in contrast
      to simple CD4/CD8-Lck complexes, not sensitive to alkylation with iodoacetamide.
      These large complexes therefore represent an alternative way of association of
      CD4 and CD8 with the protein tyrosine kinases, which may play a role in signaling
      through these receptors.

PMID- 7806283
TI  - Structural analysis of the rat T-cell receptor Tcra V4 gene family.
AB  - The rat Tcra V gene locus is only poorly characterized, although rats are widely
      used in a variety of T-cell-mediated experimental animal models. Recently, we
      described the first monoclonal antibody, G99, directed against a rat Tcra V4
      segment. We examined cDNA transcripts of G99-positively sorted T cells and show
      that the monoclonal antibody G99 most likely recognizes at least two members of
      the Tcra V4 family. Moreover, we analyzed the genomic repertoire of this VA
      family and report 15 novel Tcra V4 DNA sequences. Based on sequence and Southern
      blot analysis, the Tcra V4 family could be divided into four subgroups, which
      were also detected in mice. These findings corroborate previous findings of a
      similar genetic organization of the Tcra V loci in both species.

PMID- 7806284
TI  - The nucleotide sequence of the sheep MHC class II DNA gene.

PMID- 7806285
TI  - Dendritic cells induce HLA-DP-specific T-cell proliferation between MLR-negative
      siblings.

PMID- 7806287
TI  - Genetic basis of antigenic differences between three alleles of Ly5 (CD45) in
      mice.

PMID- 7806286
TI  - C4BPAL2: a second duplication of the C4BPA gene in the human RCA gene cluster.

PMID- 7806288
TI  - The BALB.B6-Cmv1r mouse: a strain congenic for Cmv1 and the NK gene complex.

PMID- 7806289
TI  - Molecular polymorphism in the Rt6 genes of laboratory mice correlates with the
      allotypes of the H1 minor histocompatibility system.

PMID- 7806290
TI  - A novel exogenous mammary tumor virus encoding MHC class II H2E-independent
      superantigen specific for Tcr-V beta 14.

PMID- 7806291
TI  - Peptide motifs of HLA-B38 and B39 molecules.

PMID- 7806292
TI  - Peptide motifs of HLA-B58, B60, B61, and B62 molecules.

PMID- 7806293
TI  - Primary structure of the mouse protein encoded by the Igh1e allele of the n
      haplotype.

PMID- 7806294
TI  - A novel variant of DR4 (DRB1*0421) identified in a patient with polychondritis.

PMID- 7806295
TI  - Immunoglobulin variable gene segment VH81X of the mouse is embedded in L1
      transposon sequences.

PMID- 7806296
TI  - Identification of the novel HLA-DPB1*5801 allele detected by sequenced based
      typing.

PMID- 7806298
TI  - Defining the breakpoint of a multigene deletion in the immunoglobulin heavy chain
      gene cluster.
AB  - The constant region of the human immunoglobulin heavy chain (IGHC) is encoded by
      a cluster of genes near the telomere of chromosome 14q. Deletions and
      duplications of single or multiple genes in the cluster have been identified, but
      little information about the breakpoint junctions has been available, in part due
      to the high degree of sequence similarity between the genes in this region. We
      report an intensive study of a homozygous deletion, using Southern hybridization
      and polymerase chain reaction techniques. We found that the deleted DNA includes
      the functional epsilon gene, and that the breakpoints are located within a 2
      kilobase Bam HI/Sac I region of both the IGHEP1 and IGHE genes. These results
      revise a previous conclusion regarding the deleted region. Definition of
      breakpoints occurring within this cluster may shed light on recombination
      mechanisms.

PMID- 7806297
TI  - The MHC E locus in macaques is polymorphic and is conserved between macaques and
      humans.
AB  - Although the functions of the molecules encoded by the classical MHC class I loci
      are well defined, no function has been ascribed to the molecules encoded by the
      non-classical MHC class I loci. To investigate the evolution and conservation of
      the non-classical loci, we cloned and sequenced HLA-E homologues in macaques. We
      isolated four E locus alleles from five rhesus monkeys and two E locus alleles
      from one cynomolgus monkey, which indicated that the E locus in macaques is
      polymorphic. We also compared the rate of nucleotide substitution in the second
      intron of the macaque and human E locus alleles with that of exons two and three.
      The rate of nucleotide substitution was significantly higher in the introns,
      which suggested that the E locus has evolved under selective pressure.
      Additionally, comparison of the rates of synonymous and non-synonymous
      substitutions in the peptide binding region versus the remainder of the molecule
      suggested that the codons encoding the amino acids in the peptide binding region
      had been conserved in macaques and humans over the 36 million years since
      macaques and humans last shared a common ancestor.

PMID- 7806299
TI  - Primate DRB genes from the DR3 and DR8 haplotypes contain ERV9 LTR elements at
      identical positions.
AB  - The HLA-DRB genes of the human major histocompatibility complex constitute a
      multigene family with a varying number of DRB genes in different haplotypes. To
      gain further knowledge concerning the evolutionary relationship, the complete
      nucleotide sequence was determined for a region spanning introns 4 and 5 of the
      three DRB genes (DRB1*0301, DRB2, and DRB3*0101) from a DR52 haplotype and the
      single DRB gene (DRB1*08021) in the DR8 haplotype. These analyses identified as
      endogenous retroviral long terminal repeat element (ERV9 LTR3), inserted at
      identical positions in intron 5 of the functional DRB genes in these two
      haplotypes. Comparison of the nucleotide sequence from introns 4 and 5 including
      the ERV9 LTR elements revealed a strong similarity between the three expressed
      DRB genes. The DRB3*0101 and DRB1*08021 genes were most similar in this
      comparison. These findings provide further evidence for a separate duplication in
      a primordial DR52 haplotype followed by a gene contraction event in the DR8
      haplotype. A homologous element was found in a chimpanzee DRB gene from a DR52
      haplotype. This represents the first characterized ERV9 LTR element in a nonhuman
      species. The corresponding introns of the DRB genes in the DR4 haplotype contain
      no ERV9 LTRs. In contrast, these genes have insertions of distinct Alu repeats,
      implying distinct evolutionary histories of DR52 and DR53 haplotypes,
      respectively. Phylogenetic analyses of DRB introns from DR52, DR53, and DR8
      haplotypes showed a close relationship between the DRB2 and DRB4 genes. Thus, the
      ancestral DR haplotype that evolved to generate the DR52 and DR53 haplotypes most
      likely shared a primordial common DRB gene.

PMID- 7806300
TI  - Physical mapping of the retinoid X receptor B gene in mouse and human.
AB  - Retinoid X receptors (RXRs) are zinc finger-containing nuclear transcription
      factors. They belong to the nuclear receptor superfamily that contains retinoid
      receptors, vitamin D receptors, thyroid hormone receptors, and steroid hormone
      receptors as well as the so-called orphan receptors. We previously mapped all
      three RXR genes on mouse chromosomes, using a panel of Mus spretus-Mus musculus
      interspecific backcross mice: Namely, the RXRA-gene (Rxra) on Chr 2 near the
      centromere, the RXRB gene (Rxrb) on Chr 17 in the H2 region, and the RXRG gene
      (Rxrg) on distal Chr 1. Using cosmid clones that cover the major
      histocompatibility complex (MHC) region, we determined the precise physical map
      positions of the gene encoding mouse and human RXRB, respectively. The mouse gene
      (Rxrb) maps between H2-Ke4 and H2-Ke5: namely, immediately telomeric to H2-Ke4
      which encodes a histidine-rich transmembrane protein, and 12 kilobases
      centromeric to H2-Ke5 which is expressed in lymphoid tissues. Rxrb and H2-Ke4 are
      transcribed into opposite directions from a CpG-rich promoter of about 250 base
      pairs. This gene organization is well conserved also in the human genome at the
      HLA-DP subregion of Chr 6p, underscoring the strong conservation of the gene
      organization in the MHC region between the two mammals.

PMID- 7806302
TI  - IgE levels of normal Indian children.
AB  - A number of factors, including age, sex and atopic status have been reported to
      influence levels of serum IgE. Serum samples were obtained from 350 (173 males,
      177 females) non allergic normal Indian children of 0-15 years of age. Mean serum
      IgE value was 65.8 +/- 4.0 IU/ml being significantly higher in males (75.0 +/-
      2.7 IU/ml) as compared to females (56.6 +/- 3.0 IU/ml). The levels were found to
      increase with age irrespective of sex.

PMID- 7806301
TI  - Different TCRBV genes generate biased patterns of V-D-J diversity in human T
      cells.
AB  - The aim of this work was to assess whether each T-cell receptor (TCR) BV segment
      generates a random pattern of junctional diversity or if, alternatively, biased
      patterns of V-D-J rearrangements limit the number of available TCR specificities.
      Detailed molecular analysis of T-cell receptors expressed by lymphocytes was
      obtained by generating a large number of junctional regions sequences from
      TCRBV3, TCRBV4, TCRBV5S1, TCRBV12, TCRBV13S2, TCRBV17, TCRBV20, and TCRBV22
      variable genes. The > 800 sequences analyzed have allowed the characterization of
      the recombination frequencies of each germline-encoded V, D, and J segments, as
      well as of the magnitude of exonucleolytic nibbling and of the number of N
      nucleotides inserted for each group of TCRB segments. The data obtained indicate
      that the extent of junctional diversity varies considerably depending on the
      TCRBV gene implicated in the recombination event, due to the occurrence of skewed
      patterns of J and D region usage. Furthermore, our results show that
      "illegitimate" rearrangements occur with unexpectedly high incidence,
      specifically at the level of TCRBD to TCRBJ joining. These findings provide
      additional information for a more accurate estimation of the size of the TCRBV
      repertoire and for understanding the well-established biased pattern of TCRBV
      expression in humans.

PMID- 7806304
TI  - News from Hyderabad. Indians more prone to cataract.

PMID- 7806303
TI  - Pulmonary alveolar microlithiasis with pectus excavatum. Case report.
AB  - Pulmonary alveolar microlithiasis is a rare disease of unknown etiology. There is
      a formation of calcific bodies within the alveoli. The X-Ray shows extensive
      infiltration of both lungs. So far less than 100 cases were reported. However, we
      are unware of a case with pectus excavatum. In this report we discuss a case of
      pulmonary alveolar microlithiasis with pectus excavatum, and its treatment and
      medical intervention.

PMID- 7806305
TI  - Glucose-6-phosphate dehydrogenase deficiency and its variants in India.

PMID- 7806306
TI  - DNA adducts: identification and biological significance. Proceedings of a
      meeting. Huddinge, Sweden, 18-21 November 1992.

PMID- 7806307
TI  - Reactions of polycyclic aromatic hydrocarbons with DNA.

PMID- 7806308
TI  - DNA adducts derived from safrole, estragole and related compounds, and from
      benzene and its metabolites.

PMID- 7806309
TI  - Vinyl halides, haloaldehydes and monohaloalkanes.

PMID- 7806310
TI  - DNA adducts of alpha,beta-unsaturated aldehydes and dicarbonyl compounds.

PMID- 7806311
TI  - DNA adducts of pyrrolizidine alkaloids, nitroimidazoles and aristolochic acid.

PMID- 7806312
TI  - DNA adducts of lactones, sultones, acylating agents and acrylic compounds.

PMID- 7806313
TI  - DNA adducts of carcinogenic aromatic amines.

PMID- 7806314
TI  - DNA adducts of heterocyclic aromatic amines, arylazides and 4-nitroquinoline 1
      oxide.

PMID- 7806315
TI  - DNA adducts of nitropolycyclic aromatic hydrocarbons.

PMID- 7806316
TI  - DNA damage caused by oxidation, deamination, ultraviolet radiation and
      photoexcited psoralens.

PMID- 7806317
TI  - Reaction of aralkyl halides with nucleic acid components and DNA.

PMID- 7806318
TI  - DNA adducts of N-nitrosoureas.

PMID- 7806320
TI  - From fluorescence spectra to mutational spectra, a historical overview of DNA
      reactive compounds.
AB  - This historical survey has shown the emergence over a period of about 60 years of
      a coherent view of DNA-reactive carcinogens and their effects. The earliest
      workers, in the 'pre-Watson-Crick' era, probably thought that the mode of action
      of carcinogens, then largely comprising polycyclic aromatic hydrocarbons, would
      be revealed through a relationship to steroid hormones, and that they would have
      protein receptors. This may well apply, in a broad sense, to promoting agents in
      carcinogenesis. Demonstration of the mutagenicity of a chemical, mustard gas,
      shifted attention to alkylating agents as carcinogens, and to the concept of
      mutagens, carcinogens and cytotoxic agents as 'radiomimetic'. Alkylating
      carcinogens were shown to react with DNA in vitro and in vivo in ways consistent
      with their action as mutagens, particularly as inducers of base substitutions, GC
      ->AT transitions. Carcinogenic hydrocarbons were subsequently shown to react with
      DNA of their target tissue, mouse skin, to extents positively correlated with
      their carcinogenic potency. They were found to react through aralkylating
      metabolites to give products that can block DNA polymerase, but can also cause
      base substitutions of the transversion type, mainly GC-->TA. Current interest
      centres on correlating the observed base substitutions that activate oncogenes or
      inactivate tumour suppressor genes in human cancer with the nature of exogenous
      and endogenous mutagens and the chemistry of their reactions with DNA, in order
      to deduce whether specific carcinogens can be implicated in the etiology of
      cancers. Ancillary to these studies are determinations of carcinogen-DNA reaction
      products in DNA from human sources.

PMID- 7806319
TI  - The minor groove covalent reactive drugs anthramycin and (+)-CC-1065 and their
      interstrand cross-linking derivatives.

PMID- 7806321
TI  - DNA adducts of nitrogen mustards and ethylene imines.

PMID- 7806322
TI  - DNA alkylation by triazenes and related compounds.

PMID- 7806323
TI  - DNA adducts of cisplatin, transplatin and platinum-intercalating drugs.

PMID- 7806324
TI  - DNA adducts of the mitomycins.

PMID- 7806325
TI  - Gene-specific damage and repair of DNA adducts and cross-links.

PMID- 7806326
TI  - DNA alkylation by ethylene oxide and some mono-substituted epoxides.

PMID- 7806327
TI  - Mutational spectra of endogenous genes in mammalian cells.

PMID- 7806328
TI  - Mutagenic specificity of chemical carcinogens as determined by studies of single
      DNA adducts.

PMID- 7806329
TI  - Mutational spectra of protooncogenes and tumour suppressor genes: clues in
      predicting cancer etiology.

PMID- 7806330
TI  - Structures of DNA adducts of saligeninphosphates.

PMID- 7806331
TI  - Alkylation of purine bases with 3,4-epoxy-1-butene, a reactive metabolite of 1,3
      butadiene.

PMID- 7806332
TI  - Structures of DNA adducts formed by halothioketenes and haloketenes: possible
      adducts formed from trichloro- and perchloroethene via glutathione conjugation.

PMID- 7806333
TI  - Modification of DNA by alpha-nitrosamino aldehydes.

PMID- 7806334
TI  - Synthesis and characterization of a (+)-anti-benzo[a]pyrene 7,8-dihydrodiol 9,10
      epoxide-oligonucleotide adduct.

PMID- 7806335
TI  - Mechanisms of formation of 1,N6-ethenoadenine, 3,N4-ethenocytosine, 1,N2
      ethenoguanine and N2,3-ethenoguanine DNA adducts from substituted oxiranes.

PMID- 7806336
TI  - DNA adducts of allyl compounds, enals and unsaturated ketones. Significance for
      mutagenicity and carcinogenicity.

PMID- 7806337
TI  - Formation of thymidine, cyclic deoxyguanosine and cyclic deoxycytidine adducts of
      the mutagen 2-bromoacrolein and their role in mutagenicity and clastogenicity.

PMID- 7806338
TI  - DNA adducts of aromatic amines present in tobacco smoke.

PMID- 7806339
TI  - Mutagenic specificity of acetylaminofluorene-derived DNA adducts in vitro.

PMID- 7806340
TI  - DNA adducts of aflatoxins, sterigmatocystin and other mycotoxins.

PMID- 7806341
TI  - Dihaloalkanes and polyhaloalkenes.

PMID- 7806342
TI  - DNA adducts of nitrosamines.

PMID- 7806343
TI  - Tobacco-specific nitrosamines.

PMID- 7806344
TI  - Expression of recombinant exoenzyme S of Pseudomonas aeruginosa.
AB  - The structural gene for the 49-kDa form of exoenzyme S (exoS) isolated from
      Pseudomonas aeruginosa 388 was expressed in both Escherichia coli and P.
      aeruginosa PA103. Expression of exoS in E. coli under the transcriptional
      regulation of the T7 promoter yielded a soluble cytosolic protein with an
      apparent molecular mass of 49 kDa, as determined by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. Expression of exoS in P. aeruginosa PA103
      under the transcriptional regulation of the 0.9 kbp of Pseudomonas chromosomal
      DNA flanking the 5' end of exoS yielded a nitrilotriacetic acid-inducible
      extracellular protein with an apparent molecular mass of 49 kDa. Recombinant ExoS
      (rExoS) reacted with the anti-49-kDa form of exoenzyme S immunoglobulin G,
      existed as an aggregate as determined by gel filtration chromatography, and ADP
      ribosylated soybean trypsin inhibitor at a specific activity that was similar
      (within twofold) to that of native exoenzyme S. Allelic exchange of exoS with a
      tetracycline gene cartridge yielded a strain of P. aeruginosa 388 that did not
      express detectable amounts of either ExoS in an immunoblot analysis using the
      anti-49-kDa form of exoenzyme S immunoglobulin G or ADP-ribosyltransferase
      activity under standard enzyme assay conditions. Expression of catalytically
      active rExoS in E. coli demonstrated that exoS was necessary and sufficient for
      the factor-activating exoenzyme S-dependent ADP-ribosyltransferase activity of
      exoenzyme S. Expression of nitrilotriacetic acid-inducible rExoS in P. aeruginosa
      PA103 demonstrated that the 0.9 kbp of Pseudomonas chromosomal DNA flanking the
      5' end of exoS encoded a functional exoenzyme S promoter. Expression analysis and
      allelic exchange experiments suggest that the 49- and 53-kDa forms of exoenzyme S
      are encoded by separate genes.

PMID- 7806345
TI  - Selective modulation of lipopolysaccharide-induced death and cytokine production
      by various muramyl peptides.
AB  - Pretreatment of animals with the adjuvant muramyl dipeptide enhances both the
      production of circulating tumor necrosis factor and the sensitivity to the lethal
      effect of a lipopolysaccharide (LPS) challenge. The present study examined the
      capacity of various adjuvant muramyl dipeptide derivatives to potentiate
      responsiveness to LPS administration. Cytokine levels in serum were determined at
      various time intervals after LPS administration by bioassays and immunoassays;
      the cytokines examined were tumor necrosis factor, interleukin-1, interleukin-6,
      and gamma interferon. The time course of cytokine response was not modified by
      the pretreatment, but most of the levels were strongly enhanced. However, of the
      four compounds which were found to be potent priming agents, only two caused an
      increased sensitivity to LPS lethality, showing that elevated titers of cytokines
      in serum were not correlated with host sensitization. Interestingly, previous
      studies have shown that these two compounds also display neurobiological
      properties, implying a possible role of the central nervous system in LPS
      lethality. However, two hydrophilic derivatives with low activity as priming
      agents were capable of decreasing the toxicity of LPS when given after the
      challenge in galactosamine-sensitized mice. These results illustrate the
      diversity of responses elicited by immunological priming. They raise unanswered
      questions on the importance of endogenous mediators in the pathophysiological
      alterations during toxic shock.

PMID- 7806346
TI  - Adaptive mutation and cocolonization during Helicobacter pylori infection of
      gnotobiotic piglets.
AB  - Clinical isolates of Helicobacter pylori, the gastric pathogen implicated in
      gastritis, peptic ulcers, and gastric cancer in humans, are diverse in traits
      likely to be important for colonization and disease. Here we report studies using
      a gnotobiotic piglet-H. pylori infection model to test for host-specific
      adaptation and to detect cocolonization by different strains. First, an H. pylori
      strain that initially had grown only weakly in piglets was adapted to them by
      spontaneous mutation and selection during 12 serial passages; this resulted in an
      increase in yield from about 10(3) to > 10(7) bacteria per g of mucosa. Second,
      piglets were fed mixtures of two different well-adapted strains and the presence
      of one or both strains was monitored by restriction analysis of a PCR-amplified
      flagellar (flaA) gene segment. The restriction fragment patterns from pools of
      bacteria indicated that both strains had colonized most piglets and that both
      strains were present at more than half of the individual biopsy sites, although
      often at unequal ratios. This suggests a microcolonial mode of growth with
      limited migration of bacteria between neighboring sites in the gastric mucosa. We
      propose that the gnotobiotic piglet-H. pylori infection model will be useful for
      testing how spontaneous mutation, selection, and DNA transfer between strains
      during mixed infection may each contribute to adaptation to specific hosts and
      the evolution of virulence of this important pathogen.

PMID- 7806347
TI  - Pure paraflagellar rod protein protects mice against Trypanosoma cruzi infection.
AB  - The paraflagellar rod proteins (PAR) purified from Trypanosoma cruzi
      epimastigotes were shown to protect mice against an otherwise lethal challenge
      inoculum of 10(3) bloodstream-form trypomastigotes. The injection route used for
      immunization was shown to have a marked impact on the development of protective
      immunity. Mice receiving subcutaneous (s.c.) injections of PAR proteins had
      reduced bloodstream parasitemias and showed 100% survival following challenge. In
      contrast, mice immunized via the intraperitoneal (i.p.) route developed
      parasitemia levels equivalent to those of unimmunized controls and did not
      survive infection. Western blotting (immunoblotting) demonstrated that sera from
      both i.p. and s.c. immunized mice reacted specifically with PAR proteins;
      however, the antibody titer of the i.p. immunized mice was approximately 64-fold
      greater than that of the s.c. immunized mice, suggesting that the protective
      response in the s.c. immunized mice is cell mediated rather than humoral.

PMID- 7806348
TI  - Immunomodulatory spectrum of lipids associated with Mycobacterium avium serovar
      8.
AB  - Lipid fractions obtained from Mycobacterium avium serovar 8 were assessed for the
      ability to affect various immune functions of human peripheral blood mononuclear
      cells (PBM). Lipids included a total lipid fraction and fractions eluted from
      silicic acid column separation of that total lipid fraction, using chloroform and
      chloroform-methanol combinations. Lipid fractions were assayed for total
      carbohydrate and total 6-deoxyhexose content and were assessed for the ability to
      influence human macrophage function and the capacity to induce secretion of
      prostaglandin E2 (PGE2) and tumor necrosis factor alpha in PBM. The total lipid
      and serovar-specific glycopeptidolipid (GPL) fractions both induced significant
      levels of tumor necrosis factor alpha, as well as PGE2, in PBM exposed to a
      sublethal concentration of 100 micrograms lipid per 2 x 10(6) cells. In addition,
      the same concentrations of the 5 to 7% and GPL fractions induced significant
      levels of leukotriene B4 in PBM. Comparison of carbohydrate and 6-deoxyhexose
      contents of each fraction suggested a relationship to carbohydrate content and
      ability of fractions to induce immune modulator secretion. Analysis of GPL
      fractions from M. avium serovars 4 and 20 revealed that those GPL lacked the
      ability to induce PGE2. These results are explained by considering the difference
      in the carbohydrate residues of the oligosaccharide moieties.

PMID- 7806349
TI  - Monoclonal antibodies that inhibit mitogenic activity of Mycoplasma pulmonis.
AB  - Previous studies have suggested a correlation between mitogenic, polyclonal
      activation of host lymphocytes and the respiratory tract inflammatory diseases
      induced by Mycoplasma pulmonis. This study describes the generation of monoclonal
      antibodies (MAbs) to M. pulmonis membrane antigens with different capacities to
      inhibit stimulation of cultured rat lymphocytes by mycoplasmal membranes and with
      variable effects on M. pulmonis growth. We show that the inhibitory effects
      exerted on mitogenesis by purified MAbs are inversely related to the effects of
      MAbs on M. pulmonis growth. Immunoblotting of electrophoretically separated
      membrane proteins, with both growth- and mitogenesis-inhibiting antibodies,
      revealed significant changes in the reactions obtained with both types of MAb
      following short exposure of membranes to heat. Growth-inhibiting MAbs strongly
      react with heat-labile antigenic complexes with molecular weights of 65,000 to
      75,000. Inhibition of mitogenesis is mainly associated with recognition of
      membrane complexes of 84 to 113 kDa that exhibit disperse smears and variable
      heat sensitivities. Following brief heating of membranes, more distinct bands of
      103, 90, and 84 kDa are obtained with MAbs that inhibit mitogenesis. Experiments
      with other mitogenic mycoplasma species and MAb 3.3.10.2, a potent inhibitor of
      mitogenesis reveal that whereas the antigenic epitope recognized by this antibody
      is present on unheated membranes from different mycoplasmas, with heated
      membranes the MAb yields reactions only with M. pulmonis and M. arthritidis. Our
      studies suggest that M. pulmonis mitogens are unique membrane complexes of
      variable molecular weights, highly susceptible to heat and less sensitive to
      reducing agents.

PMID- 7806350
TI  - Isolation of extracytoplasmic proteins from Serpulina hyodysenteriae B204 and
      molecular cloning of the flaB1 gene encoding a 38-kilodalton flagellar protein.
AB  - Extracytoplasmic proteins were released from Serpulina (Treponema) hyodysenteriae
      (strain B204) by treatment of whole cells with a nonionic detergent (Tween 20).
      Centrifugation of the Tween 20-released proteins at 100,000 x g sedimented 10
      major extracytoplasmic proteins with approximate molecular masses of 44, 43.5,
      42, 39, 38, 34, 33.5, 33, 31, and 29 kDa. Treatment of the sedimented fraction
      with 6 M urea solubilized all of the proteins except the 39-kDa protein. Peptide
      sequences were obtained for the purified 42-, 39-, 38-, 34-, 31-, and 29-kDa
      proteins. The peptide sequences of the 42-, 38-, and 31-kDa proteins indicate
      that they likely are components of the periplasmic flagella. The amino-terminal
      peptide sequence of the 38-kDa protein was used to design an oligonucleotide
      probe and to clone an S. hyodysenteriae DNA fragment containing the gene encoding
      this protein. The predicted 290-amino-acid protein sequence derived from the
      cloned gene was highly homologous to those of several other bacterial flagellar
      proteins and is preceded by consensus sigma D nucleotide sequences found upstream
      of other flagellar genes. On the basis of its similarity to the FlaB proteins of
      other spirochetes, we propose to designate the cloned S. hyodysenteriae gene
      flaB1 and its encoded protein FlaB1. Vaccination of pigs with FlaB1 or its
      recombinant counterpart did not protect them from an experimental challenge.

PMID- 7806352
TI  - Heat stress alters the virulence of a rifampin-resistant mutant of Francisella
      tularensis LVS.
AB  - We have studied the stress response of a rifampin-resistant mutant of Francisella
      tularensis LVS. This mutant, Rif 7, was avirulent with an intraperitoneally
      administered 50% lethal dose greater than 10(7) CFU in a murine model of
      infection. Exposure of Rif 7 to heat stress for 5 h in vitro resulted in a 2-log
      decrease in its 50% lethal dose (P < 0.02). The increase in virulence was
      dependent on the time of exposure to high temperature and was maximal at 5 h.
      Envelope preparations from heat-stressed cells showed increased levels of several
      proteins. Notable among these were polypeptides with approximate molecular masses
      of 16, 60, and 75 kDa. Increases in both virulence and envelope protein levels
      were reversed when heat-treated cells were subsequently grown at 37 degrees C.
      Inhibition of protein synthesis by actinomycin D during heat stress blocked the
      increase in virulence of Rif 7. Cell-free media from the heat-stressed Rif 7
      reacted with the whole spectrum of bacterial proteins were not toxic to mice.
      Hyperimmune serum against Rif 7 reacted with the whole spectrum of bacterial
      proteins in Western blots (immunoblots), although its reaction with 34- and 45
      kDa proteins and two 60- and 75-kDa proteins upregulated during heat stress was
      weak. Other stress conditions, low iron and low pH, caused similar increases in
      the virulence of Rif 7. However, examination of the protein profile did not
      reveal any major common polypeptides induced by different stresses. Heat-treated
      Rif 7 bacteria were fully able to replicate in macrophages in vitro and in the
      host tissues, even though heat treatment only partially restored virulence.

PMID- 7806351
TI  - Location of the complement factor H binding site on streptococcal M6 protein.
AB  - The surface M protein of group A streptococci binds factor H, a regulatory
      protein of the alternative complement pathway, which may contribute to the
      antiphagocytic activity of the M molecules. To locate the factor H binding domain
      in the alpha-helical coiled-coil structure of the M molecule, the M protein was
      cleaved with pepsin at pH 5.8, which separates the molecule approximately in
      half. Western blot (immunoblot), amino acid sequence, and mass spectrometric
      analyses revealed that factor H bound to a 14.6-kDa C-terminal fragment of the M
      molecule. Competitive inhibition of factor H binding to the 14.6-kDa fragment
      with M protein peptides localized the binding site to amino acids 256 to 292.
      This segment is located within the surface-exposed region of the M6 protein,
      identified as the C-repeat region, whose sequence is conserved among heterologous
      M and M-like molecules. These studies also identified a second pepsin-susceptible
      site with the sequence ELAK located within the cell wall-associated region of the
      M molecule.

PMID- 7806354
TI  - Monophosphoryl lipid A behaves as a T-cell-independent type 1 carrier for hapten
      specific antibody responses in mice.
AB  - It is known that the lipopolysaccharide (LPS) of gram-negative bacteria, in
      addition to being a potent adjuvant, is an effective carrier for covalently
      associated haptens. However, the toxic nature of most forms of LPS precludes
      their use as adjuvants or carriers for human vaccines. 4'-Monophosphoryl lipid A
      (MLA), a derivative of LPS with attenuated toxicity, is currently being tested in
      humans as an immunological adjuvant. In this study, MLA was tested for its
      ability to function as a carrier for a small hapten, the trinitrophenyl group
      (TNP). MLA was first modified by addition of 6-aminocaproic acid to the 6'
      position of the disaccharide backbone (Cap-MLA). TNP was then attached to Cap-MLA
      via the free amino group, yielding TNP-Cap-MLA. Immunization of normal mice with
      TNP-Cap-MLA resulted in high-titer anti-TNP responses of immunoglobulin M and all
      immunoglobulin G subclasses. Furthermore MLA, like other T-cell-independent type
      1 (TI-1) carriers, induced responses in athymic and X-linked immunodeficient
      mice. In all cases, immunization with either MLA alone or TNP-Cap plus MLA failed
      to induce measurable anti-TNP antibodies of any isotype, indicating that covalent
      association of MLA and hapten was necessary for MLA's carrier activity to be
      manifested. These properties of MLA make it a potential candidate as a carrier
      for vaccine subunit components, such as small peptides, especially for situations
      in which T-cell help is impaired, as occurs following human immunodeficiency
      virus type 1 infection.

PMID- 7806353
TI  - Neisserial porins inhibit human neutrophil actin polymerization, degranulation,
      opsonin receptor expression, and phagocytosis but prime the neutrophils to
      increase their oxidative burst.
AB  - Porins are trimeric proteins that constitute water-filled pores that allow
      transmembrane diffusion of small solutes through the outer membrane layer of gram
      negative bacteria. The porins are capable of inserting into the membranes of
      eucaryotic cells, and in the present study we have examined the in vitro effects
      on neutrophil functions of the following purified porins: meningococcal outer
      membrane protein classes 1 and 3 and gonococcal outer membrane protein 1B (P1B).
      The neisserial porins inhibited human neutrophil chemoattractant-induced actin
      polymerization and degranulation of both primary and secondary granules. The
      neutrophil expression of immunoglobulin G (IgG) Fc receptors II (Fc gamma RII;
      CDw32) and III (Fc gamma RIII; CD16), as well as the activation-dependent
      downregulation of Fc gamma RIII, were reduced by the meningococcal and gonococcal
      porins. The neisserial porins impaired the upregulation of complement receptors 1
      (CD35) and 3 (CD11b) and inhibited the phagocytic capacity of neutrophils, as
      evaluated by the uptake of meningococci (strain 44/76) in the presence of patient
      serum containing known amounts of IgG against meningococcal porins. The porins
      also primed neutrophils to increase their intracellular hydrogen peroxide
      production in response to FMLP, whereas no such priming was observed if the
      neutrophil protein kinase C was stimulated directly with phorbol myristate
      acetate. The neisserial porins influenced neutrophil functions in a time- and
      concentration-dependent manner. The meningococcal class 1 outer membrane protein
      and the gonococcal P1B tended to alter neutrophil functions more than the
      meningococcal class 3 protein. Thus, the neisserial porins inhibited human
      neutrophil actin polymerization, degranulation, opsonin receptor expression, and
      phagocytosis but primed the neutrophils to increase their oxidative burst. It
      remains to be determined whether these in vitro observations reflect mechanisms
      that may be of importance for the interaction between neutrophils and Neisseria
      species in vivo.

PMID- 7806355
TI  - The enterotoxin of Bacteroides fragilis is a metalloprotease.
AB  - During the past decade, strains of Bacteroides fragilis that produce an
      enterotoxin have been implicated in diarrheal disease in animals and humans. The
      extracellular enterotoxin has been purified and characterized as a single
      polypeptide (M(r), approximately 20,000). Single specific primer-PCR was used to
      clone a portion of the B. fragilis enterotoxin gene. The recombinant protein
      expressed by the cloned gene fragment reacted with monospecific antibodies to B.
      fragilis enterotoxin by enzyme-linked immunosorbent assay and immunoblot
      analysis. The deduced amino acid sequence revealed a signature zinc-binding
      consensus motif (HEXXHXXGXXH/Met-turn) characteristic of metalloproteases termed
      metzincins. Sequence comparisons showed close identity to matrix metalloproteases
      (e.g., human fibroblast collagenase) within the zinc-binding and Met-turn region.
      Purified enterotoxin contained 1 g-atom of Zn2+ per molecule and hydrolyzed
      gelatin, azocoll, actin, tropomyosin, and fibrinogen. The enterotoxin also
      underwent autodigestion. The N-terminal amino acid sequences of two autodigestion
      products were identical to the deduced amino acid sequence of the recombinant
      enterotoxin and revealed cleavage at Cys-Leu and Ser-Leu peptide bonds.
      Gelatinase (type IV collagenase) activity comigrated with the toxin when analyzed
      by gel fractionation and zymography, indicating that protease activity is due to
      the enterotoxin and not to a contaminating protease(s). Optimal proteolytic
      activity occurred at 37 degrees C and pH 6.5. Primary proteolytic cleavage sites
      in actin were identified, revealing cleavage at Gly-Met and Thr-Leu peptide
      bonds. Enzymatic activity was inhibited by metal chelators but not by inhibitors
      of other classes of proteases. Additionally, cytotoxic activity of the
      enterotoxin on human carcinoma HT-29 cells was inhibited by acetoxymethyl ester
      EDTA. The metalloprotease activity of the enterotoxin suggests a possible
      mechanism for enterotoxicity and may have additional implications in the study of
      disease caused by B. fragilis.

PMID- 7806356
TI  - Inhibition of Listeria locomotion by mosquito oostatic factor, a natural
      oligoproline peptide uncoupler of profilin action.
AB  - Mosquito oostatic factor, a naturally occurring decapeptide (YDPAPPPPPP),
      strikingly resembles the primary structure of oligoproline-rich regions within
      the protein ActA, a bacterial surface protein required for Listeria motility in
      host cells. When microinjected into Listeria-infected PtK2 cells, the insect
      oostatic factor rapidly blocks Listeria-induced actin rocket tail assembly as
      well as intracellular locomotion of this pathogen. At intracellular
      concentrations of about 90 nM, transient inhibition of rocket tail formation and
      bacterial locomotion occurs, followed by full recovery of tail length and
      motility. However, at 0.9 microM oostatic factor, both processes are permanently
      arrested. Introduction of oostatic factor by microinjection also causes PtK2
      peripheral membrane retraction in both Listeria-infected and uninfected cells.
      Epifluorescence microscopy with bodipy-phallacidin reveals that cells
      microinjected with the insect factor lose all actin stress fibers and accumulate
      F-actin in regions of membrane retraction. When the insect peptide is combined
      with profilin as an equimolar binary solution (1 microM [final concentration]
      each), intracellular addition fails to inhibit Listeria rocket-tail formation,
      fails to block intracellular bacterial movement, and no longer causes marked
      membrane retraction. The ability of profilin to neutralize the inhibitory action
      of oostatic factor is consistent with complex formation, and this finding
      suggests that profilin may interact directly with ActA peptide as well as a host
      cell peripheral membrane component to promote actin filament assembly by locally
      generating ATP-actin. Dispersal of profilin from such sites by oligoproline-rich
      peptide inhibitors suggests that profilin is directly involved in intracellular
      pathogen locomotion and reorganization of actin cytoskeleton of the host cell
      peripheral membrane.

PMID- 7806357
TI  - Effect of enteropathogenic Escherichia coli on adherent properties of Chinese
      hamster ovary cells.
AB  - Enteropathogenic Escherichia coli (EPEC) O111:H2, O119:H6, or O142:H6 caused
      rapid detachment of Chinese hamster ovary (CHO) cell monolayers within 2 to 4 h
      of cocultivation. CHO cell detachment was not promoted by nonenteropathogenic E.
      coli (O125:H4, O126:H27, O157:H7, and O26:H11) and could not be attributed to
      EPEC production of enterohemolysin or Shiga-like toxins. In contrast, EPEC
      strains did not promote rapid detachment of Lec1, Lec2, or Lec8 CHO cell
      monolayers. These CHO cell Lec mutants all express abbreviated glycan sequences
      on membrane glycoproteins and glycolipids. Although EPEC strains failed to alter
      the adherent properties of Lec2 cells lacking only terminal sialic acid groups,
      EPEC adherence to the Lec2 mutant was indistinguishable from that observed with
      wild-type CHO cells. There was also no significant difference in EPEC-induced
      actin accumulation or invasion of Lec2 cells. In contrast, EPEC localized
      adherence to Lec1 and Lec8 mutants, lacking sialyllactosamine (Lec1) or sialic
      acid and galactose (Lec8) sequences, was reduced by 84 and 93%, respectively. Our
      results suggest that lactosamine sequences [beta Gal(1-4 or 1-3)beta GlcNAc] not
      containing sialic acid are sufficient for EPEC adherence, actin accumulation, and
      invasion of CHO cells. Sialic acid groups, however, may be necessary for EPEC
      mediated CHO cell detachment.

PMID- 7806358
TI  - Reactivation of persistent Chlamydia trachomatis infection in cell culture.
AB  - Gamma interferon induces persistent chlamydial infections in cell culture. These
      infections are characterized by altered morphologic and biochemical features of
      the pathogen. These persistent forms are abnormally large and noninfectious and
      undergo unusual structural and functional changes, including production of a
      paucity of outer envelope constituents and normal levels of the chlamydial hsp60,
      an immunopathological antigen. The current investigation evaluates the events
      that occur during reactivation of infectious Chlamydia trachomatis from
      persistently infected cell cultures. Transfer of persistent chlamydial organisms
      to gamma interferon-free medium resulted in recovery of infectivity accompanied
      by an increase in levels of structural membrane proteins and reorganization of
      aberrant organisms to morphologically typical elementary bodies. In addition,
      reactivation of infectious organisms from persistent chlamydiae that were
      maintained in culture for several weeks was demonstrated. These studies show that
      persistent C. trachomatis maintains viability for extended periods, illustrate
      the reversibility of immunologically mediated persistent infections, and
      characterize reactivation at the ultrastructural and biochemical levels.

PMID- 7806359
TI  - Molecular and biochemical characterization of a protective 40-kilodalton antigen
      from Corynebacterium pseudotuberculosis.
AB  - A 40-kDa protein from Corynebacterium pseudotuberculosis has been previously
      identified as a protective antigen against ovine caseous lymphadenitis. From
      genomic DNA libraries of C. pseudotuberculosis, we have cloned and sequenced the
      40-kDa protein gene, which was found to contain an open reading frame of 1,137 bp
      encoding a protein of 379 amino acids. No significant homology with previously
      published DNA or amino acid sequence data was found in databases, suggesting that
      this is a novel protein. Recombinant 40-kDa protein was overexpressed as a fusion
      protein to 15% of total cell proteins in Escherichia coli. Biochemical analysis
      of native and recombinant 40-kDa proteins has revealed associated proteolytic
      activity, which was shown to be of the serine protease type through the use of
      specific inhibitors. We suggest that this novel protective antigen be termed
      corynebacterial protease 40 (CP40).

PMID- 7806360
TI  - A 135-kilodalton surface antigen of Mycoplasma hominis PG21 contains multiple
      directly repeated sequences.
AB  - A monoclonal antibody was used to characterize a 135-kDa surface-located membrane
      protein (Lmp1) generally present in Mycoplasma hominis strains. The monoclonal
      antibody, 552, was applied to identify the corresponding gene in an expression
      library of M. hominis PG21 DNA. The M. hominis PG21 lmp1 gene was sequenced, and
      its gene product was characterized with the goal of elucidating the structure and
      function of Lmp1. A total of 7,196 bp in the lmp1 region was sequenced. An open
      reading frame of 4,032 bp, encoding a protein of 1,344 amino acids with a
      calculated molecular weight of 147,000, was identified. Analysis of the deduced
      amino acid sequence predicted a hydrophilic protein with a basic pI (10.0). The N
      terminal 24 amino acids were a typical leader sequence. Downstream from the first
      726 nucleotides, six similar direct repeats of 471 nucleotides were found. In
      repeat 7, a single-base substitution, C-->A, gave rise to the stop codon of lmp1.
      Thus, the C-terminal 945 amino acids were encoded by the 471-bp direct repeats.
      As evidenced by Southern blot analysis, the gene encoding the 135-kDa antigen is
      part of a multigene family. One of the genes, lmp2, was situated directly
      downstream from lmp1 where the direct repeats continued.

PMID- 7806362
TI  - Revised sequence of the Porphyromonas gingivalis prtT cysteine
      protease/hemagglutinin gene: homology with streptococcal pyrogenic exotoxin
      B/streptococcal proteinase.
AB  - The prtT gene from Porphyromonas gingivalis ATCC 53977 was previously isolated
      from an Escherichia coli clone possessing trypsinlike protease activity upstream
      of a region encoding hemagglutinin activity (J. Otogoto and H. Kuramitsu, Infect.
      Immun. 61;117-123, 1993). Subsequent molecular analysis of this gene has revealed
      that the PrtT protein is larger than originally reported, encompassing the
      hemagglutination region. Results of primer extension experiments indicate that
      the translation start site was originally misidentified. An alternate open
      reading frame of nearly 2.7 kb, which encodes a protein in the size range of 96
      to 99 kDa, was identified. In vitro transcription-translation experiments confirm
      this size, and Northern (RNA) blot experiments indicate that the protease is
      translated from a 3.3-kb mRNA. Searching the EMBL protein database revealed that
      the amino acid sequence of the revised PrtT is similar to sequences of two
      related proteins from Streptococcus pyogenes. PrtT is 31% identical and 73%
      similar over 401 amino acids to streptococcal pyrogenic exotoxin B. In addition,
      it is 36% identical and 74% similar over 244 amino acids with streptococcal
      proteinase, which is closely related to streptococcal pyrogenic exotoxin B. The
      similarity is particularly high at the putative active site of streptococcal
      proteinase, which is similar to the active sites of the family of cysteine
      proteases. Thus, we conclude that PrtT is a 96- to 99-kDa cysteine protease and
      hemagglutinin with significant similarity to streptococcal enzymes.

PMID- 7806361
TI  - Induction of transforming growth factor beta 1 by purified protein derivative of
      Mycobacterium tuberculosis.
AB  - We examined the ability of purified protein derivative (PPD) of Mycobacterium
      tuberculosis to induce transforming growth factor beta 1 (TGF-beta 1), a potent
      immunosuppressive and macrophage-deactivating molecule, in blood monocytes from
      healthy individuals. TBF-beta 1 activity in PPD-induced monocyte supernatants was
      identified by Western immunoblot analysis and was not inhibited by polymyxin B,
      an inhibitor of bacterial lipopolysaccharide (LPS). Furthermore, PPD at
      equivalent amounts in weight to LPS was as potent in stimulation of monocyte
      production of TGF-beta 1 at 24 h of culture, as quantified by enzyme-linked
      immunosorbent assay. The inducing effect of PPD, in contrast to that of LPS, was
      sustained at later time points of culture (72 h). PPD enhanced the constitutive
      expression of TGF-beta 1 steady-state mRNA in monocytes at 24 and 48 h of
      culture. In contrast, neither mycobacterial heat shock protein (64-kDa protein of
      M.bovis) nor LPS induced TGF-beta 1 mRNA. Decay studies suggested a
      transcriptional rather than a posttranscriptional effect of PPD on TGF-beta 1
      gene expression.

PMID- 7806363
TI  - Promotion of cytotoxic T-cell generation in mixed leukocyte culture by
      phosphatidylinositol-specific phospholipase C from Bacillus thuringiensis.
AB  - Phosphatidylinositol-specific phospholipase C (PIPLC) from Bacillus
      thuringiensis, which cleaves phosphatidylinositol or glycosylphosphatidylinositol
      on the external cell surface to generate a second messenger for intracellular
      signal transduction (S. Rahman et al., FEBS Lett. 303:193-196, 1992), was found
      to preferentially promote the generation of alloantigen-specific cytotoxic T
      lymphocytes in mixed leukocyte culture. PIPLC affected an early stage of
      cytotoxic T-lymphocyte activation in culture, and there was no evidence of any
      soluble cellular mediators of this PIPLC action. PIPLC neither enhanced overall
      cell proliferation nor noticeably promoted interleukin-2 and -4 production in
      mixed leukocyte culture. The relative population size of Ly-2+ T cells was
      increased, however, in a late mixed leukocyte culture with PIPLC. In addition,
      PIPLC enhanced an anti-CD3 monoclonal antibody-induced early increase in [Ca2+]i.
      These results suggest a new parasite (bacterium)-oriented mechanism for enhancing
      antigen-driven host cytotoxic T-lymphocyte immunity which does not include
      promotion of interleukin-2 production.

PMID- 7806364
TI  - Comparison of immune responses and resistance to brucellosis in mice vaccinated
      with Brucella abortus 19 or RB51.
AB  - Immune responses and resistance to infection with Brucella abortus 2308 (S2308)
      were measured in mice following vaccination with B. abortus 19 (S19) or the
      lipopolysaccharide (LPS) O-antigen-deficient mutant, strain RB51 (SRB51). Live
      bacteria persisted for 8 weeks in spleens of mice vaccinated with 5 x 10(6) or 5
      x 10(8) CFU of SRB51, whereas bacteria persisted for 12 weeks in mice vaccinated
      with 5 x 10(6) CFU of S19. Mice vaccinated with 5 x 10(6) or 5 x 10(8) CFU of
      SRB51 had increased resistance to infection with S2308 at 12, 16, and 20 weeks
      after vaccination, but the resistance was lower than that induced by vaccinating
      mice with 5 x 10(6) CFU of S19. Spleen cells obtained from mice vaccinated with
      S19 or SRB51 generally exhibited similar proliferative responses to S2308
      bacteria or bacterial proteins (106 to 18 kDa) following challenge of mice with
      S2308 at 12, 16, or 20 weeks after vaccination. Mice vaccinated with S19 had
      antibody to S2308 bacteria and S2308 smooth LPS at 4, 8, and 12 weeks after
      vaccination. In contrast, mice vaccinated with either dose of SRB51 did not
      produce antibody to S2308 smooth LPS. In addition, only mice vaccinated with the
      highest dose of SRB51 (5 x 10(8) CFU) had antibody responses to S2308 bacteria,
      although the responses were lower and less persistent than those in mice
      vaccinated with S19. Collectively, these results indicate that SRB51-vaccinated
      mice have similar cell-mediated immune responses to S2308 but lower resistance to
      infection with S2308 compared with S19-vaccinated mice. The lower resistance in
      SRB51-vaccinated mice probably resulted from a combination of rapid clearance of
      SRB51 and an absence of antibodies to S2308 LPS.

PMID- 7806365
TI  - Knockout mutants of Actinobacillus pleuropneumoniae serotype 1 that are devoid of
      RTX toxins do not activate or kill porcine neutrophils.
AB  - The Actinobacillus pleuropneumoniae RTX-toxins ApxI, ApxII, and ApxIII are
      important virulence factors of this swine pathogen. It is hypothesized that the
      Apx toxins are deleterious to defense cells of the host, enabling the bacterium
      to infect the host. To confirm this, we studied the effect on porcine
      polymorphonuclear neutrophils of mutant strains of A. pleuropneumoniae that were
      devoid of Apx toxins. For this purpose, we developed a system for targeted
      mutagenesis of A. pleuropneumoniae based on the conditionally replicating plasmid
      pVE6063 and insertional mutagenesis by homologous recombination. Employing this
      system on the reference strain of serotype 1, a strain that secretes ApxI and
      ApxII, we generated mutant strains that were devoid of ApxI and/or ApxII. We
      compared the ability of the parent strain and the mutant strains to provoke an
      oxidative burst in porcine neutrophils and to kill these cells. The parent strain
      and mutants that secreted either ApxI or ApxII provoked an oxidative burst and
      killed the neutrophils, whereas mutant strains that were devoid of ApxI and ApxII
      did not. These experiments indicate the importance of ApxI and ApxII to these
      profound effects on neutrophils and emphasize the importance of ApxI and ApxII in
      pathogenesis.

PMID- 7806366
TI  - Group B streptococci (GBS) injure lung endothelium in vitro: GBS invasion and GBS
      induced eicosanoid production is greater with microvascular than with pulmonary
      artery cells.
AB  - Neonatal group B streptococcal (GBS) sepsis and pneumonia cause lung endothelial
      cell injury. GBS invasion of the lung endothelium may be a mechanism for injury
      and the release of vasoactive eicosanoids. Pulmonary artery endothelial cells
      (PAEC) and lung microvascular endothelial cells (LMvEC) were isolated from
      neonatal piglets and were characterized as endothelial on the basis of
      morphology, uptake of acyl low-density lipoprotein, factor VIII staining, and
      formation of tube-like structures on Matrigel. PAEC and LMvEC monolayers were
      infected with COH-1 (parent GBS strain), isogenic mutants of COH-1 devoid of
      capsular sialic acid or all capsular polysaccharide, or a noninvasive Escherichia
      coli strain, DH5 alpha. Intracellular GBS were assayed by plate counting of
      colony-forming units resistant to incubation with extracellular antibiotics. All
      GBS strains invaded LMvEC significantly more than PAEC, showing that the site of
      lung endothelial cell origin influences invasion. DH5 alpha was not invasive in
      either cell type. Both isogenic mutants invaded PAEC and LMvEC more than COH-1
      did, showing that GBS capsular polysaccharide attenuates invasion. Live GBS
      caused both LMvEC and PAEC injury as assessed by lactate dehydrogenase release;
      heat-killed GBS and DH5 alpha caused no significant injury. Supernatants from
      PAEC and LMvEC were assayed by radioimmunoassay for prostaglandin E2 (PGE2), the
      stable metabolite of prostacyclin (6-keto-PGF1 alpha), and the thromboxane
      metabolite thromoxane B2. At 4 h, live COH-1 caused no significant increases in
      eicosanoids from both PAEC and LMvEC. At 16 h, live COH-1, but not heat-killed
      COH-1, caused a significant increase in 6-keto-PGF1 alpha greater than PGE2 from
      LMvEC, but not PAEC. We conclude that live GBS injure and invade the lung
      microvascular endothelium and induce release of prostacyclin and PGE2. We
      postulate that GBS invasion and injury of the lung microvasculature contribute to
      the pathogenesis of GBS disease.

PMID- 7806367
TI  - Noninhibitory binding of human interleukin-2-activated natural killer cells to
      the germ tube forms of Candida albicans.
AB  - During incubation in vitro with yeast or germ tube forms of Candida albicans,
      only 2 to 6% of freshly isolated human natural killer (NK) cells (> 85% CD16+,
      CD56+, CD3-; < 15% CD3+; cytolytic for the NK-susceptible target K562 but not for
      the NK-resistant target DAUDI), were seen to interact with the fungal cells. As
      seen under the electron microscope, the contact area had a limited extent and was
      narrow, and neither the surface nor the intracytoplasmic organization of the NK
      cell was altered. In contrast, more than 30% of interleukin-2-activated NK (LAK)
      cells (> 96% CD16+, CD56+, CD3-; 1.5% CD3+; cytolytic for both K562 and DAUDI
      targets) interacted closely with the fungus. This interaction was particularly
      extensive with the surface of the fungal germ tube that was intimately enveloped
      by villous protrusions from the lymphocyte surface. The fungus-interacting LAK
      cell also showed a remarkable redistribution of surface microvilli and
      polarization of cytoplasmic organelles, such as the Golgi apparatus, centrioles,
      and granules, toward the area of fungal contact. Together with the elevated
      cytolytic potential against the K562 and DAUDI targets, all the morphological
      data suggested the presence of a potentially active lytic machinery in the fungus
      interacting LAK cell. Nonetheless, two independent assays for anticandidal
      activity did not show consistent killing or fungal growth inhibition by either
      fresh NK or LAK cells. While offering direct evidence of the strong interaction
      between human LAK cells and the germ tubes, precursors of tissue-invasive hyphal
      forms of C. albicans, our observations also suggest that this interaction may not
      be sufficient to kill the fungus or arrest its growth.

PMID- 7806368
TI  - Persistence of local cytokine production in shigellosis in acute and convalescent
      stages.
AB  - Shigella infection is accompanied by an intestinal activation of epithelial
      cells, T cells, and macrophages within the inflamed colonic mucosa. A prospective
      study was carried out to elucidate the cytokine pattern in Shigella infection
      linked to development of immunity and eradication of bacteria from the local site
      and also to correlate the cytokine profile with histological severity. An
      indirect immunohistochemical technique was used to determine the production and
      localization of various cytokines at the single-cell level in cryopreserved
      rectal biopsies from 24 patients with either Shigella dysenteriae type 1 (n = 18)
      or Shigella flexneri (n = 6) infection. The histopathological profile included
      presence of chronic inflammatory cells with or without neutrophils and
      microulcers in the lamina propria, crypt distortion, branching, and less
      frequently crypt abscesses. Patients had significantly higher (P < 0.005) numbers
      of cytokine producing cells for all of the cytokines studied, interleukin-1 alpha
      (IL-1 alpha), IL-1 beta, IL-1ra, tumor necrosis factor alpha (TNF-alpha), IL-6,
      IL-8, IL-4, IL-10, gamma interferon, TNF-beta, and transforming growth factor
      beta 1-3, in the biopsies than the healthy controls (n = 13). The cytokine
      production profile during the study period was dominated by IL-1 beta,
      transforming growth factor beta 1-3, IL-4, and IL-10. Significantly increased
      frequencies of cytokine-producing cells (P < 0.05) were observed for IL-1, IL-6,
      gamma interferon, and TNF-alpha in biopsies with severe inflammation in
      comparison with those with mild inflammation. During the acute stage of the
      disease, 20 of 24 patients exhibited acute inflammation in the rectal biopsies
      and the cellular infiltration was still extensive 30 days after the onset of
      diarrhea, although the disease was clinically resolved. In accordance with the
      histological findings, cytokine production was also upregulated during the
      convalescent phase; there was no significant difference (P > 0.05) in the
      incidence of cytokine-producing cells between acute (2 to 8 days after the onset
      of diarrhea) and convalescent (30 days after onset) stages.

PMID- 7806369
TI  - Tumor necrosis factor (TNF)-dependent shedding of the p55 TNF receptor in a
      baboon model of bacteremia.
AB  - We have tested the hypothesis that the tumor necrosis factor (TNF) plays a
      significant role in vivo in TNF receptor shedding and studied the release of TNF
      binding protein 1 (TNF-BP1), the soluble fragment of the 55- to 60-kDa TNF alpha
      (TNF) receptor, in a baboon model of Escherichia coli bacteremia, using three
      different doses of bacteria in acute infection (8 h) experiments (n [animals] =
      11) and a single dose in a subchronic infection (72 h) experiment. In the
      subchronic infection study, one group of animals (n = 6) was pretreated with a
      neutralizing murine monoclonal antibody to TNF (CB0006). Concentrations of TNF
      and TNF-BP1 in plasma were determined in specific, monoclonal antibody-based
      immunoassays. Untreated animals (n = 6) showed undetectable TNF concentrations (<
      10 pg/ml at baseline), whereas TNF-BP1 levels in plasma were in the range of 2
      ng/ml, similar to concentrations observed in humans. Infusion of bacteria
      resulted in a rapid, dose-dependent increase in plasma TNF concentrations that
      reached a maximal level after 2 h and returned to baseline within 6 h. TNF-BP1
      concentrations also showed a dose-dependent increase to peak concentrations three
      to fivefold above baseline within 2 h but, in contrast to TNF levels, remained
      significantly elevated for up to 48 h. In animals pretreated with antibody
      CB0006, circulating TNF was completely neutralized, and TNF-BP1 was significantly
      reduced. We conclude that TNF-BP1 is released in bacteremia and that release in
      vivo is partially dependent on the presence of TNF.

PMID- 7806370
TI  - Expression and purification of Shiga-like toxin II B subunits.
AB  - Shiga-like toxins (SLTs), which are produced by certain strains of Escherichia
      coli, are composed of enzymatically active A and B subunit multimers responsible
      for the toxin's binding. We have previously purified large amounts of the SLT-I B
      subunit by using a hyperexpression vector in Vibrio cholerae under the control of
      the trc promoter. In this study we examined various expression vectors to
      maximize yields of the SLT-II B subunit. The SLT-II B subunit has been expressed
      by using both the T7 promoter and the tac promoter in E. coli. When expressed
      from a plasmid containing the structural gene for SLT-II B deleted of the leader
      sequence, SLT-II B was able to form multimers when cross-linked, although SLT-II
      B production from this plasmid was unreproducible. SLT-II B expressed in all
      three systems appeared to form unstable multimers, which did not readily bind to
      a monoclonal antibody which preferentially recognizes B subunit multimers. SLT-II
      B expression was not increased by moving any of the plasmids into V. cholerae.
      Polyclonal antibodies raised to SLT-II B in rabbits recognized B subunit in SLT
      II holotoxin yet were poorly neutralizing. SLT-II B was also expressed as a
      fusion protein with maltose-binding protein and could be cleaved from maltose
      binding protein with factor Xa. Although the expression vectors were able to make
      large amounts of SLT-II B, as determined by Western blotting (immunoblotting),
      the levels of purified SLT-II B subunit were low compared with those obtained
      previously for SLT-I B subunit, probably because of instability of the multimeric
      SLT-II B subunit.

PMID- 7806371
TI  - Nonlethal adherence to human neutrophils mediated by Dr antigen-specific adhesins
      of Escherichia coli.
AB  - Uropathogenic Escherichia coli strains express a variety of adhesins, including
      members of the Dr adhesin family such as the Dr hemagglutinin, AFAI, and AFAIII.
      Certain E. coli adhesins (e.g., type 1 and S fimbriae) are known to mediate
      adherence to human polymorphonuclear leukocytes (PMNs). The receptor on
      erythrocytes for Dr family adhesins, decay accelerating factor, is also present
      on PMNs. To determine whether Dr family adhesins mediate adherence to PMNs and to
      characterize the specificity and consequences of such adherence, we studied
      agglutination of PMNs and adherence to PMNs by recombinant E. coli strains
      expressing various mannose-resistant or mannose-sensitive adhesins, in the
      presence or absence of inhibitors of adherence. Dr family adhesins, like type 1
      fimbriae, mediated concentration-dependent adherence to PMNs. Adherence to PMNs
      was mannose sensitive for type 1 fimbriae but mannose resistant for Dr family
      adhesins. Chloramphenicol inhibited PMN adherence for the Dr hemagglutinin with
      the same potency as that with which it inhibited hemagglutination, but it was
      inactive against PMN adherence and hemagglutination mediated by other members of
      the Dr adhesin family. In contrast to PMN adherence mediated by type 1 fimbriae,
      adherence mediated by the Dr hemagglutinin did not lead to significantly
      increased bacterial killing. These data suggest that Dr family adhesins mediate a
      novel pattern of adherence to PMNs, probably by recognizing decay accelerating
      factor, with minimal consequent bacterial killing.

PMID- 7806372
TI  - Cytoskeletal requirements in Chlamydia trachomatis infection of host cells.
AB  - Infection of genital epithelial cells by the closely related sexually transmitted
      pathogens Chlamydia trachomatis serovars E and L2 results in different clinical
      disease manifestations. Following entry into target host cells, individual
      vesicles containing chlamydiae fuse with one another to form one large inclusion.
      At the cellular level, the only obvious difference between these serovars is the
      time until inclusion maturation, which is 48 h for the invasive serovar L2 and 72
      h for serovar E. To begin to define the intracellular events of these pathogens,
      the effect of cytoskeletal disruption on early endosome fusion and inclusion
      development in epithelial (HEC-1B) and fibroblast (McCoy) cells was analyzed by
      fluorescence microscopy. Disruption of microfilaments with cytochalasin D
      markedly reduced serovar E, but not serovar L2, infection of both cell lines.
      Conversely, microfilament as well as microtubule disruption, with colchicine or
      nocodazole, had no effect on serovar E inclusion development but resulted in the
      formation of multiple serovar L2 inclusions per cell during early and mid
      development. Later in serovar L2 inclusion development (> 36 h postinfection),
      vesicles containing chlamydiae fused to form one large inclusion in the absence
      of an intact cytoskeleton. These results imply that (i) C. trachomatis serovar E
      may utilize a different pathway for uptake and development from serovar L2; (ii)
      these differences are consistent in both epithelial cells and fibroblasts; and
      (iii) the cytoskeleton plays a unique role in the infection of host cells by
      these two genital pathogens.

PMID- 7806373
TI  - Role of endotoxin in acute inflammation induced by gram-negative bacteria:
      specific inhibition of lipopolysaccharide-mediated responses with an amino
      terminal fragment of bactericidal/permeability-increasing protein.
AB  - A recombinant 23-kDa amino-terminal fragment of human bactericidal/permeability
      increasing protein (rBPI23), a potent lipopolysaccharide (LPS)
      binding/neutralizing protein, was used as a probe to assess the role of endotoxin
      in the acute inflammatory responses elicited by gram-negative bacteria in rat
      subcutaneous air pouches. In initial experiments, rBPI23 prevented the
      Escherichia coli O111:B4 LPS-induced accumulation of polymorphonuclear leukocytes
      (PMN), tumor necrosis factor alpha (TNF-alpha), and nitrite (a stable end product
      of nitric oxide formation) in exudate fluids. Significant inhibition of TNF-alpha
      production was still evident when rBPI23 treatment was delayed for 30 min after
      LPS instillation. In subsequent experiments, rBPI23 also prevented the nitrite
      and early (2-h) TNF-alpha accumulation induced by three different strains of
      formaldehyde-killed gram-negative bacteria (E. coli O7:K1, E. coli O111:B4, and
      Pseudomonas aeruginosa 12.4.4) but did not inhibit the PMN or late (6-h) TNF
      alpha accumulation induced by these bacteria. As with LPS challenge, a
      significant inhibition of early TNF-alpha production was still evident when
      rBPI23 treatment was delayed for 30 to 60 min after instillation of killed
      bacteria. The results indicate that in this experimental model the NO and early
      TNF-alpha responses to gram-negative bacterial challenge are mediated
      predominantly by endotoxin, whereas the PMN and late TNF-alpha responses may be
      mediated by other bacterial components. Moreover, the results indicate that
      rBPI23 can inhibit the bacterially induced production of certain potentially
      harmful mediators (TNF-alpha and NO) without entirely blocking the host defense,
      i.e., PMN response, against the bacteria.

PMID- 7806374
TI  - The primary structure of Clostridium septicum alpha-toxin exhibits similarity
      with that of Aeromonas hydrophila aerolysin.
AB  - The gene for Clostridium septicum alpha-toxin was cloned and expressed in
      Escherichia coli from C. septicum BX96. The toxin was determined to be 443 amino
      acids in length, with a 31-residue signal peptide that was removed from the toxin
      during secretion. No extended hydrophobic regions were observed in the mature
      toxin sequence. Expression of alpha-toxin in E. coli BL21 resulted in the
      production of ATpro, which was identical to native toxin from C. septicum with
      respect to activity and activation. The proteolytic activation site for alpha
      toxin was determined to be on the carboxy-terminal side of arginine 398, which
      lies within the sequence KKRRGKR-398SVD. Previous work showing similarities in
      activation and mechanism between alpha-toxin and Aeromonas hydrophila aerolysin
      was extended to the primary structures of both toxins. The DNA-derived primary
      sequence of alpha-toxin exhibited 27% identity and 72% similarity over a 387
      residue region with the primary structure of the A. hydrophila aerolysin toxin, a
      level of similarity heretofore unobserved between toxins produced by a gram
      positive organism and a gram-negative organism.

PMID- 7806375
TI  - Expression of the Arp protein, a member of the M protein family, is not
      sufficient to inhibit phagocytosis of Streptococcus pyogenes.
AB  - Many Streptococcus pyogenes immunoglobulin-binding proteins have structural
      similarities to the antiphagocytic M protein, including the well-known C repeats.
      One of these molecules is the immunoglobulin A-binding protein Arp, which is
      expressed by a serotype 4 strain for which no antiphagocytic M protein has yet
      been described. We expressed Arp4 in an S. pyogenes strain from which the
      structural gene for the M protein has been deleted and found that Arp4 is not
      sufficient to inhibit phagocytosis.

PMID- 7806376
TI  - Immunization of cattle with recombinant Babesia bovis merozoite surface antigen
      1.
AB  - Cattle immunized with a recombinant merozoite surface antigen-1 molecule (MSA-1)
      produced high-titered antibody that reacted with the surface of the parasite and
      neutralized merozoite infectivity in vitro. However, recombinant MSA-1
      immunization did not confer protection against challenge with virulent Babesia
      bovis. These results indicate that antibody-mediated neutralization of merozoite
      infectivity in vitro, at least for MSA-1-specific antibody, does not reflect in
      vivo protective immunity to babesiosis.

PMID- 7806377
TI  - Pseudomonas aeruginosa infection of the cornea and asialo GM1.
AB  - Extensive immunohistochemical and thin-layer chromatogram-immunostain analyses
      were carried out to establish whether asialo GM1, a glycolipid which contains
      binding sites for Pseudomonas aeruginosa, is present in corneal epithelium. The
      data suggest that rabbit corneal epithelium does not contain detectable levels of
      asialo GM1 even after corneas are scarified and incubated with trypsin, P.
      aeruginosa, or P. aeruginosa exoproducts to expose potential cryptic sites.
      Preliminary immunohistochemical analyses indicated that asialo GM1 is also not
      found in human corneas.

PMID- 7806378
TI  - Rapid disruption of epithelial barrier function by Salmonella typhimurium is
      associated with structural modification of intercellular junctions.
AB  - Short-term infection of MDCK II monolayers with Salmonella typhimurium SL1344
      caused a progressive decrease in transepithelial electrical resistance
      concomitant with decreased cation permselectivity and increased paracellular
      inulin flux. Cytochemical staining of F-actin, E-cadherin, and ZO-1 revealed the
      concentration of each junctional protein in invaded cells as a result of
      contraction at their apical poles and resultant distortion of adjacent uninvaded
      cells.

PMID- 7806379
TI  - Comparison of Cryptosporidium parvum and Cryptosporidium wrairi by reactivity
      with monoclonal antibodies and ability to infect severe combined immunodeficient
      mice.
AB  - Twenty-three monoclonal antibodies raised to Cryptosporidium parvum and 12 raised
      to C. wrairi reacted with equal intensity with the heterologous species. Despite
      demonstration of a close immunologic relationship between these two species, C.
      wrairi did not induce persistent infection in severe combined immunodeficient
      mice as did C. parvum.

PMID- 7806380
TI  - Immunoreactivity and bioactivity of lipopolysaccharide-binding protein in normal
      and heat-inactivated sera.
AB  - The lipopolysaccharide (LPS)-potentiating effect of serum is due to LPS-binding
      protein (LBP), which facilitates the binding of LPS to CD14 receptors. We
      observed a remarkable heat sensitivity of recombinant LBP and various sera with
      respect to both immunoreactivity (measured by enzyme-linked immunosorbent assay)
      and bioactivity (potentiation of LPS induction of tumor necrosis factor in
      monocytes). Human sera were more active and more heat sensitive than fetal bovine
      sera. The commonly practiced heat inactivation of human serum (56 degrees C, 30
      min) resulted in a 70% loss of bioactivity, which caused an apparent decrease in
      the potency of LPS.

PMID- 7806381
TI  - Rickettsia conorii entry into Vero cells.
AB  - The entry of rickettsiae into eukaryotic cells is mediated by an induced
      phagocytosis, but rickettsiae have never been observed in a closed phagocytic
      vacuole. In this study, Rickettsia conorii entry into Vero cells was observed by
      transmission electron microscopy during a period of 3 to 20 min after bacterium
      cell contact. The entry occurred within 3 min after bacterium-cell contact, and
      R. conorii was observed in the process of engulfment, within a phagocytic
      vacuole, or free in the cytosol. Escape from the phagosome is a very rapid step
      since phagosome lysis was only occasionally observed. By 12 min, 90% of bacteria
      were internalized and half were free in the cytosol. This report confirms that
      rickettsiae penetrate nonphagocytic cells by induced phagocytosis and is the
      first demonstration of rickettsiae within a complete phagocytic vacuole.

PMID- 7806382
TI  - Epitope mapping of the Pseudomonas aeruginosa major outer membrane porin protein
      OprF.
AB  - The Pseudomonas aeruginosa major outer membrane protein OprF has been proposed
      for use as a vaccine and as a target for immunotherapeutic and diagnostic
      monoclonal antibodies. The well-conserved epitopes for 10 surface-reactive, OprF
      specific monoclonal antibodies were localized by both overlapping peptide
      analysis and immunodetection of OprF peptides generated by cyanogen bromide and
      the protease papain. Three of the monoclonal antibodies bound to specific
      overlapping octapeptides, which had been synthesized on 160 pins to cover the
      entire 326 amino acids of OprF. The highest reactivities were as follows: MA7-1
      to the pin with attached peptide GTYETGNK (amino acids 55 to 62), MA7-2 to
      NLADFMKQ (amino acids 237 to 244), and MA5-8 to TAEGRAIN (amino acids 307 to
      314). The other monoclonal antibodies showed no reactivity, indicating that they
      do not recognize linear epitopes. Two polyclonal sera were also tested and
      demonstrated weak reactivity with discrete regions of OprF, suggesting that the
      majority of antibodies produced might recognize conformational epitopes.
      Utilizing defined peptides generated with cyanogen bromide and papain, the
      conformational epitopes recognized by the seven monoclonal antibodies were
      localized to regions that were 42 to 90 amino acids long. These regions were
      located on two adjacent loops in the middle of an amended structural model of
      OprF.

PMID- 7806383
TI  - Lipophosphoglycan blocks attachment of Leishmania major amastigotes to
      macrophages.
AB  - Promastigotes of the intracellular protozoan parasite Leishmania major invade
      mononuclear phagocytes by a direct interaction between the cell surface
      lipophosphoglycan found on all Leishmania species and macrophage receptors. This
      interaction is mediated by phosphoglycan repeats containing oligomers of beta (1
      3)Gal residues specific to L. major. We show here that although amastigotes also
      use lipophosphoglycan to bind to both primary macrophages and a cell line, this
      interaction is independent of the beta (1-3)Gal residues employed by
      promastigotes. Binding of amastigotes to macrophages could be blocked by intact
      lipophosphoglycan from L. major amastigotes as well as by lipophosphoglycan from
      promastigotes of several other Leishmania species, suggesting involvement of a
      conserved domain. Binding of amastigotes to macrophages could be blocked
      significantly by the monoclonal antibody WIC 108.3, directed to the
      lipophosphoglycan backbone. The glycan core of lipophosphoglycan could also
      inhibit attachment of amastigotes, but to a considerably lesser extent. The
      glycan core structure is also present in the type 2 glycoinositolphospholipids
      which are expressed on the surface of amastigotes at 100-fold-higher levels than
      lipophosphoglycan. However, their inhibitory effect could not be increased even
      when they were used at a 300-fold-higher concentration than lipophosphoglycan,
      indicating that lipophosphoglycan is the major macrophage-binding molecule on
      amastigotes of L. major. In the presence of complement, the attachment of
      amastigotes to macrophages was not altered, suggesting that lipophosphoglycan
      interacts directly with macrophage receptors.

PMID- 7806384
TI  - Molecular and structural requirements of a lipoteichoic acid from Enterococcus
      hirae ATCC 9790 for cytokine-inducing, antitumor, and antigenic activities.
AB  - Comparison was made between the immunobiological and antigenic properties of two
      lipoteichoic acid (LTA) fractions (LTA-1 and -2) from Enterococcus hirae ATCC
      9790, their glycolipid portions, and synthetic compounds partially mimicking the
      above bacterial products. The more lipophilic LTA-2 fraction was capable of
      inducing serum tumor necrosis factor alpha and interleukin-6 in muramyldipeptide
      primed mice and serum gamma interferon in those primed with Propionibacterium
      acnes. The LTA-2 fraction also induced tumor necrosis factor alpha, interleukin
      6, and thymocyte-activating factor (essentially interleukin-1) in murine
      peritoneal macrophage cultures. Consecutive intravenous injections of
      muramyldipeptide and the LTA-2 fraction in Meth A fibrosarcoma-bearing BALB/c
      mice caused hemorrhagic necrosis and marked regression leading to complete
      regression of the tumor with no accompanying weakening or lethal effects. The LTA
      2 fraction was at least 10,000-fold less pyrogenic in rabbits than a reference
      endotoxic lipopolysaccharide. The more hydrophilic LTA-1 fraction, on the other
      hand, showed at most marginal activity in the in vivo and in vitro assays.
      Natural glycolipids (NGL-1 and -2) which were prepared from a chloroform-methanol
      extract of Streptococcus pyogenes and E. hirae cells, and comparable in structure
      to the lipid moieties of the LTA-1 and -2 fractions, respectively, were
      practically inactive in all of the assays. None of the test synthetic compounds
      was immunobiologically active, although synthetic partial counterparts of the
      structure of LTA proposed by W. Fischer (Handb. Lipid Res. 6:123-234, 1990)
      reacted with murine monoclonal antibody TS-2, which was raised against OK-432, a
      penicillin-killed S. pyogenes preparation, and capable of neutralizing the
      cytokine-inducing activities of the LTA-2 fraction.

PMID- 7806385
TI  - Fetal outcome in murine Lyme disease.
AB  - Lyme disease is an inflammatory syndrome caused by infection with Borrelia
      burgdorferi. Although this syndrome has important implications for human
      pregnancy, little is known about gestational infection with B. burgdorferi. Fetal
      death occurred in 33 of 280 gestational sacs (12%) in 39 C3H/HeN female mice
      infected by intradermal injection of B. burgdorferi 4 days after mating (acute
      infection), compared with 0 of 191 sacs in 25 control mice (P = 0.0001). Forty
      six percent of acutely infected mice suffered at least one fetal death, compared
      with none of the control animals (P = 0.0002). There were no fetal deaths in 18
      C3H/HeN mice infected 3 weeks prior to mating (chronic infection). A sensitive
      PCR technique detected B. burgdorferi DNA in the uteri of acutely infected mice
      but did not detect DNA in the uteri of controls or chronically infected mice.
      Spirochete DNA was only rarely detected in fetal tissues, and its presence was
      not required for fetal death. The inclusion of an internal competitive PCR target
      indicated that the lack of B. burgdorferi sequences in fetal DNA was not due to
      the presence of a PCR inhibitor. Histologic analysis of gestational tissues from
      infected animals demonstrated nonspecific pathology consistent with fetal death.
      These findings indicate an association between murine fetal death and acute
      infection with B. burgdorferi early in gestation but not with chronic infection.
      Our data suggest that fetal death is due to a maternal response to infection
      rather than fetal infection. These findings could provide an explanation for
      observations in humans in which sporadic cases of fetal death in women infected
      with B. burgdorferi during pregnancy have been reported, while previous infection
      has not been associated with fetal death.

PMID- 7806386
TI  - Human immunoglobulin G (IgG) Fc receptor IIA (CD32) polymorphism and IgG2
      mediated bacterial phagocytosis by neutrophils.
AB  - Human immunoglobulin G (IgG) Fc receptor IIa (Fc gamma RIIa; CD32) is expressed
      on phagocytes, triggers phagocytosis, and represents the sole Fc receptor for IgG
      (Fc gamma R) capable of interaction with IgG2, the main IgG subclass induced in
      response to bacterial capsular polysaccharides. The two genetically determined
      structurally different allotypes of human Fc gamma RIIa, the products of the Fc
      gamma RIIa-R131 and IIa-H131 alleles, have functionally different reactivities
      with human IgG2. In humans, the Fc gamma RIIa-H131 allotype is known to interact
      efficiently with complexed human IgG2, whereas the IIa-H131 allotype does so only
      poorly. This polymorphism may therefore have implications for IgG2-mediated
      phagocytosis of encapsulated bacteria and susceptibility to bacterial infections.
      Phagocytosis of IgG2-opsonized bacteria by homozygous Fc gamma RIIa-R/R131,
      heterozygous IIa-H/R131, and homozygous IIa-H/H131 polymorphonuclear cells (PMN)
      was compared. A higher phagocytic capacity of IgG2-opsonized group B type III
      streptococci by PMN of homozygous H/H131 individuals compared with PMN from
      homozygous R/R131 individuals was observed (P = 0.001), while heterozygous IIa
      H/R131 PMN showed intermediate phagocytosis. In this model system, IgG2-mediated
      phagocytosis was independent of the Fc gamma RIIIb-NA1/NA2 allelic polymorphism.

PMID- 7806387
TI  - Proteolytic activation of bacterial toxins by eukaryotic cells is performed by
      furin and by additional cellular proteases.
AB  - Before intoxication can occur, anthrax toxin protective antigen (PA), Pseudomonas
      exotoxin A (PE), and diphtheria toxin (DT) must be activated by proteolytic
      cleavage at specific amino acid sequences. Previously, it was shown that PA and
      DT can be activated by furin. In Chinese hamster ovary (CHO) cells, wild-type
      (RKKR) and cleavage site mutants of PA, each administered with a modified form of
      anthrax toxin lethal factor (the N terminus of lethal factor fused to PE domain
      III), had the following potencies: RKKR (wild type) (concentration causing 50%
      cell death [EC50] = 12 ng/ml) > or = RAAR (EC50 = 18 ng/ml) > FTKR (EC50 = 24
      ng/ml) > STRR (EC50 = 49 ng/ml). In vitro cleavage of PA and cleavage site
      mutants of PA by furin demonstrated that native PA (RKKR) and PA with the
      cleavage sequence RAAR are substrates for furin. To characterize eukaryotic
      proteases that play a role in activating bacterial toxins, furin-deficient CHO
      cells were selected after chemical mutagenesis. Furin-deficient cells were
      resistant to PE, whose cleavage site, RQPR, constitutes a furin recognition site
      and to all PA cleavage site mutants, but were sensitive to DT (EC50 = 2.9 ng/ml)
      and PA (EC50 = 23 ng/ml), whose respective cleavage sites, RKKR and RVRR, contain
      additional basic residues. Furin-deficient cells that were transfected with the
      furin gene regained sensitivity to PE and PA cleavage site mutants. These studies
      provide evidence that furin can activate the three toxins and that one or more
      additional proteases contribute to the activation of DT and PA.

PMID- 7806388
TI  - Fibronectin-binding antigen 85 and the 10-kilodalton GroES-related heat shock
      protein are the predominant TH-1 response inducers in leprosy contacts.
AB  - Peripheral blood mononuclear cells from 27 healthy leprosy contacts were analyzed
      for lymphoproliferation and TH-1 cytokine secretion (interleukin-2 and gamma
      interferon) in response to heat shock proteins with molecular masses of 65, 18,
      and 10 kDa from Mycobacterium leprae and the 30-32-kDa antigen 85 (Ag 85) from
      Mycobacterium bovis BCG. Cells from 18 and 19 of 19 lepromin-positive contacts
      proliferated or produced TH-1 cytokines in response to the M. leprae 10-kDa
      protein and to Ag 85, respectively. Limiting-dilution analysis for two lepromin
      positive contacts indicated that about one-third of M. leprae-reactive T cells
      displayed specificity to the M. leprae 10-kDa protein and Ag 85. The M. leprae 65
      and 18-kDa proteins were less potent TH-1 response inducers: gamma interferon
      and interleukin-2 could be measured in 14 and 19 lepromin-positive contacts,
      respectively. In contrast, very low or undetectable proliferative and cytokine
      responses were found for 8 lepromin-negative contacts. Our data demonstrate that
      the fibronectin-binding Ag 85 and the 10-kDa GroES homolog are powerful
      mycobacterial TH-1 response inducers in the vast majority of lepromin-positive
      contacts and suggest that they might be valuable candidates for a future subunit
      vaccine.

PMID- 7806389
TI  - The group A streptococcal virR49 gene controls expression of four structural vir
      regulon genes.
AB  - Within a genomic locus termed the vir regulon, virR genes of opacity factor
      nonproducing (OF-) group A streptococci (GAS) are known to control the expression
      of the genes encoding M protein (emm) and C5a peptidase (scpA) and of virR
      itself. Within the corresponding genomic locus, opacity factor-producing (OF+)
      GAS harbor additional emm-related genes encoding immunoglobulin G- and
      immunoglobulin A-binding proteins (fcrA and enn, respectively). The virR gene
      region of the OF+ GAS M-type 49 strain CS101 was amplified by PCR, and 2,650 bp
      were directly sequenced. An open reading frame of 1,599 bp exhibited 76% overall
      homology to published virR sequences. By utilizing mRNA analysis, the 5' ends of
      two specific transcripts were mapped 370 and 174 bp upstream of the start codon
      of this open reading frame. The deduced sequences of the corresponding promoters
      and their locations differed from those of previously reported virR promoters.
      Transcripts from wild-type fcrA49, emm49, enn49, and scpA49 genes located
      downstream of virR49 were characterized as being monocistronic. The transcripts
      were quantified and mapped for their 5' ends. Subsequently, the virR49 gene was
      inactivated by specific insertion of a nonreplicative pSF152 vector containing
      recombinant virR49 sequences. The RNA from the resulting vir-mut strain did not
      contain transcripts of virR49, fcrA49, emm49, or enn49 and contained reduced
      amounts of the scpA49 transcript when compared with wild-type RNA. The mRNA
      control from the streptokinase gene was demonstrated not to be affected. When
      strain vir-mut was rotated in human blood, it was found to be fully sensitive to
      phagocytosis by human leukocytes. Thus, the present study provides evidence that
      virR genes in OF+ GAS could be involved in the control of up to five vir regulon
      genes, and their unaffected regulatory activity is associated with features
      postulated as crucial for GAS virulence.

PMID- 7806390
TI  - Analysis of expression of CagA and VacA virulence factors in 43 strains of
      Helicobacter pylori reveals that clinical isolates can be divided into two major
      types and that CagA is not necessary for expression of the vacuolating cytotoxin.
AB  - Colonization of the mucosa of the stomach and the duodenum by Helicobacter pylori
      is the major cause of acute and chronic gastroduodenal pathologies in humans.
      Duodenal ulcer formation strongly correlates with the expression of an antigen
      (CagA) that is usually coeexpressed with the vacuolating cytotoxin (VacA), a
      protein that causes ulceration in the stomach of mice. However, the relationship
      between these two virulence factors is unknown. To define whether CagA and VacA
      are coexpressed in all clinical isolates and their relationships, we collected 43
      clinical isolates of H. pylori and studied their genetic and phenotypic
      properties. Based on this analysis, most of the strains could be classified into
      two major types. Type I bacteria had the gene coding for CagA and expressed the
      CagA protein and the vacuolating cytotoxin. Type II bacteria did not have the
      gene coding for CagA and did not express either the CagA protein or the
      vacuolating cytotoxin. Type I and type II bacteria represented 56 and 16%,
      respectively, of the 43 clinical isolates, while the remaining 28% had an
      intermediate phenotype, expressing CagA independently of VacA or vice versa. This
      finding shows that although it is present in most cytotoxic strains, CagA is not
      necessary for the expression of the vacuolating cytotoxin.

PMID- 7806391
TI  - Analysis of immunization route-related variation in the immune response to heat
      killed Salmonella typhimurium in mice.
AB  - In examinations of the factors regulating the quality and quantity of the immune
      response to Salmonella typhimurium, we have shown previously that live and heat
      killed preparations of S. typhimurium can induce gamma interferon-dominant and
      interleukin-4-dominant immune responses, respectively, upon intraperitoneal
      (i.p.) immunization of BALB/c mice. Using this system to investigate the role of
      the route of immunization in the immune response, we show in the present study
      that i.p. immunization with heat-killed S. typhimurium generates a quantitatively
      better immune response than does intradermal (i.d.) immunization. The
      quantitative differences observed between the i.p. and i.d. routes are apparent
      in the amount of S. typhimurium-specific antibodies produced, the extent of
      responses in T-cell proliferation assays, and the quantities of lymphokines
      generated. However, the ratios of immunoglobulin (Ig) isotypes [IgG1/IgG2a] are
      comparable and the relative dominance of interleukin-4 over gamma interferon is
      seen in both i.p.- and i.d.-immunized mice, suggesting that the predominant T
      cell effector pathways triggered are not qualitatively dependent on the route of
      immunization. An examination of the antigenic profile recognised by the B-cell
      and T-cell responses in i.p.- versus i.d.-immunized mice shows that while the
      Western immunoblot patterns recognized by serum antibodies from the two groups of
      mice were not significantly different, T cells from i.p.-immunized mice
      recognized a broader spectrum of antigens in an immunoblot assay than did those
      from i.d.-immunized mice. These data suggest that there may be a significant
      difference in the antigen-processing ability of peritoneal and dermal antigen
      presenting cells for complex antigenic formulations such as bacterial vaccines.

PMID- 7806392
TI  - Mortality of Dutch workers exposed to carbon disulfide.
AB  - Epidemiological studies carried out in Great Britain, Scandinavia and the United
      States indicate that workers exposed to carbon disulfide are at an increased risk
      for cardiovascular disease (CVD) mortality, and in particular for ischemic heart
      disease (IHD) mortality. In the epidemiological study reported here a
      retrospective cohort design was used. The total study population consisted of
      3322 workers from a Dutch viscose textile plant who had all been employed for at
      least half a year between 1 January 1947 and 1 January 1980. Only production and
      maintenance workers were selected for the study. A group of 1434 workers who had
      been exposed to carbon disulfide was identified from the files available at the
      plant. The remaining 1888 workers who had not been exposed to carbon disulfide
      were used as a reference group. The total study population was followed for
      mortality until 1 January 1988. For the 762 workers who had died before that
      date, the causes of death were checked at the Central Bureau of Statistics. The
      results show a slightly but significantly increased risk for CVD mortality (CVD
      specific SMR of 115), despite the observation of the so-called healthy worker
      effect and the statistical uncertainties inherent to this type of study. The
      results are in accordance with those reported by other investigators. The results
      indicate that exposure to relatively low levels of carbon disulfide increases the
      risk of CVD mortality.

PMID- 7806393
TI  - Frequencies of occupational allergic diseases and gender differences in Finland.
AB  - In Finland occupational diseases are registered by diagnosis, causative agent,
      age, occupation, field of work, and gender. This report analyzes in detail the
      1991 statistics on gender differences in occupational allergic diseases. A total
      of 1314 cases of occupational allergic diseases were reported, comprising 14.2%
      of all registered occupational diseases. The following allergic occupational
      diseases were encountered: allergic contact dermatitis (412 cases), bronchial
      asthma (352), allergic rhinitis (319), contact urticaria/protein contact
      dermatitis (146), and allergic alveolitis (85). The number of cases of allergic
      alveolitis (men, 42 cases; women, 43 cases) and bronchial asthma (176 men/176
      women) was about equal in both genders. Women were overrepresented in allergic
      rhinitis (195 women/124 men), allergic contact dermatitis (247 women/165 men),
      and contact urticaria/protein contact dermatitis (109 women/37 men). According to
      current knowledge, there are no great gender differences in the development of
      asthma or allergic rhinitis. The greater number of women with occupational
      respiratory allergy and immediate skin allergy may indicate that women in Finland
      are more exposed to type I allergens than men. The greater number of cases of
      allergic contact dermatitis in women may reveal women's predisposition to delayed
      type allergy, or women's greater occupational exposure to contact allergens.

PMID- 7806394
TI  - Surveillance of occupational illness through a national poison control center: an
      approach to reach small-scale enterprises?
AB  - A pilot study was performed in order to evaluate the usefulness of the Swiss
      Toxicological Information Center (STIC) in detecting cases of occupational
      illness. One hundred and fifty-two symptomatic occupational exposure cases were
      collected, comprising 3.2% of 4830 cases reported to the STIC between 1 April
      1992 and 15 August 1992. In 114 cases a follow-up could be performed by a
      structured telephone interview. On the basis of these interview data it was
      estimated that 72% of the cases in small enterprises were reported to the STIC
      without additional notification to an occupational insurance fund. By contrast,
      only 28% of the occupational illness cases that occurred in companies employing
      more than 15 workers were not reported to an occupational insurance fund. This
      discrepancy could have resulted in part from the fact that occupational insurance
      in Switzerland is mandatory only for salaried employees, not for self-supporting
      persons. It is concluded that the monitoring of the occurrence of occupational
      illnesses in small-scale enterprises must be improved. Poison control centers
      could play a major role in this respect.

PMID- 7806395
TI  - Volatile organic compounds in the blood of persons in Kuwait during the oil
      fires.
AB  - Between March and November of 1991, approximately 9000 workers from 43 different
      countries battled the burning oil wells in Kuwait. To document the exposure of
      persons in Kuwait during the oil well fires to volatile organic compounds (VOCs),
      we obtained samples of blood from 14 U.S. personnel in Kuwait City in May of 1991
      (group I) and 40 American firefighters working in the oil fields in October of
      1991 (group II). Concentrations of VOCs in group I and group II were compared
      with those of a random sample of 114 persons in the United States (reference
      group). The median concentrations of VOCs in group I were equal to or lower than
      those in the reference group. We found significant differences between the median
      concentrations of several VOCs in group II and the reference group. Median levels
      of ethylbenzene were about 10 times higher among group II than among the
      reference group (0.53 microgram/l vs 0.052 microgram/l). Median levels of
      benzene, m-/p-xylene, o-xylene, styrene, and toluene among group II were more
      than double those of the reference group. Although firefighters had higher median
      concentrations of VOCs than the reference group, those American personnel in
      Kuwait not involved in fighting the oil fires had concentrations of VOCs
      comparable to those in the reference group. Blood VOC measurements indicate a
      significant increase in exposure to VOCs in firefighters, but do not demonstrate
      this in personnel in Kuwait City.

PMID- 7806396
TI  - Occupational asthma caused by decorative flowers: review and case reports.
AB  - Occupational respiratory symptoms caused by decorative flowers are seldom
      reported in the literature. In the years 1985-1993 four such cases of
      occupational asthma were diagnosed at the Institute of Occupational Health of
      Finland. Occupational asthma was caused by freesias (n = 1), chrysanthemums (n =
      1), and tulips (n = 2). The diagnoses were based on work-related respiratory
      symptoms during flower handling in the patients' histories, specific challenge
      tests, and allergologic examinations. Flower allergy is rare but can even develop
      into occupational asthma. It usually leads to a change of profession.

PMID- 7806398
TI  - Changing emphasis in occupational toxicology: are we ready?

PMID- 7806397
TI  - Diagnostic value of finger thermometry and photoplethysmography in the assessment
      of hand-arm vibration syndrome.
AB  - Digital photoplethysmography and skin thermometry are both measures of
      circulation in the skin of the fingers. These methods and a cold provocation test
      were performed on 29 chain-saw workers grouped in stages 0, 1, 2, or 3 according
      to the Stockholm Workshop scale of hand-arm vibration syndrome, and on 16
      controls. The reduction of photoplethysmographic amplitude after the cold test
      reflects the degree of vasoconstriction, and the recovery rate demonstrates
      passive vasodilatative capacity. Both tests were found to distinguish all
      vibration--exposed subjects, including those without clinically manifest
      vibration-induced white fingers, from the controls. With a 75% reduction in
      photoplethysmographic amplitude as a discriminating threshold, the sensitivity
      for the detection of Raynaud's phenomenon was 62% and the specificity, 87%. The
      discriminating threshold of 90% for recovery rate yielded a sensitivity of 69%
      and a specificity of 72%.

PMID- 7806399
TI  - Dose-response relationship for radiation carcinogenesis in the low-dose region.
AB  - Evidence that low-level radiation substantially enhances the effectiveness of
      repair mechanisms is summarized. This finding destroys the theoretical basis
      (there is no other basis) for use of a linear-no threshold dose-response
      relationship to estimate the cancer risk of exposure to low-level radiation. Such
      a methodology will exaggerate the risk. This conclusion is further supported by
      epidemiological evidence and by studies of the effects of radon exposure in the
      home, which are reviewed.

PMID- 7806400
TI  - Evaluation of an exposure setup for studying effects of diesel exhaust in humans.
AB  - Diesel exhaust is a common air pollutant and work exposure has been reported to
      cause discomfort and affect lung function. The aim of this study was to develop
      an experimental setup which would allow investigation of acute effects on
      symptoms and lung function in humans exposed to diluted diesel exhaust. Diluted
      diesel exhaust was fed from an idling lorry through heated tubes into an exposure
      chamber. During evaluations of the setup we found the size and the shape of the
      exhaust particles to appear unchanged during the transport from the tail pipe to
      the exposure chamber. The composition of the diesel exhaust expressed as the
      ratios CO/NO, total hydrocarbons/NO, particles/NO, NO2/NO, and formaldehyde/NO
      were almost constant at different dilutions. The concentrations of NO2 and
      particles in the exposure chamber showed no obvious gradients. New steady state
      concentrations in the exposure chamber were obtained within 5-7 min. In a
      separate experiment eight healthy nonsmoking subjects were exposed to diluted
      exhaust at a median steady state concentration of 1.6 ppm NO2 for the duration of
      1 h in the exposure chamber. All subjects experienced unpleasant smell, eye
      irritation, and nasal irritation. Throat irritation, headache, dizziness, nausea,
      tiredness, and coughing were experienced by some subjects. Lung function was not
      found to be affected during the exposure. The experimental setup was found to be
      appropriate for creating different predetermined steady state concentrations in
      the exposure chamber of diluted exhaust from a continuously idling vehicle. The
      acute symptoms reported by the subjects were relatively similar to what patients
      reported at different workplaces.

PMID- 7806401
TI  - Dietary habits, a non-negligible source of 2-thiothiazolidine-4-carboxylic acid
      and possible overestimation of carbon disulfide exposure.
AB  - 2-Thiothiazolidine-4-carboxylic acid (TTCA) is the accepted urinary indicator of
      occupational exposure to carbon disulfide. This compound was detected in blank
      urine of individuals unexposed to carbon disulfide during an experimental
      validation of a new method of determination. Diet was suspected to be the source
      of TTCA, and particularly the consumption of brassica vegetables. This assumption
      was confirmed by collection and analysis of urine samples after ingestion of
      crude cabbage. TTCA was detected at concentrations higher than 2 mg/l in urine,
      and 3 mg/kg in crude cabbage. The identity of TTCA was confirmed after extraction
      and separation by capillary electrophoresis, supercritical fluid chromatography,
      and mass spectrometry. The results show that the diet should be considered as a
      nonnegligible source of the overestimation of carbon disulfide exposure.

PMID- 7806402
TI  - An enzyme-linked immunosorbent assay for hippuric acid: its potential application
      for biological monitoring of toluene exposure.
AB  - An enzyme-linked immunosorbent assay (ELISA) for hippuric acid (HA) was developed
      using polyclonal anti-HA antibodies. Anti-HA antibodies were obtained by
      immunizing rabbits with N-benzoyl-cysteine (B-Cys) or N-alpha-benzoyl-lysine (B
      Lys). An antibody with highest reactivity to HA was obtained from anti-B-Lys
      antiserum by affinity chromatography with B-Cys-Sepharose. The ELISA system was
      composed of solid-phase B-Cys, anti-HA antibody, and horseradish peroxidase
      conjugated anti-rabbit immunoglobulin antibody. The detection limit of the ELISA
      for HA was around 1 microgram/ml. The urinary HA concentration determined by the
      ELISA system correlated well with that obtained by high-performance liquid
      chromatography (HPLC). The ELISA system was considered to be useful in the
      biological monitoring of toluene exposure, and to be more advantageous than time
      consuming HPLC, especially when measuring a large number of samples.

PMID- 7806403
TI  - Application of a new, self-recording, vibratory sensation meter to measure
      temporary threshold shift of vibratory sensation caused by local vibration
      exposure.
AB  - A new, self-recording, vibratory sensation meter measures temporary threshold
      shifts of vibratory sensation (TTSv) on a finger tip. After exposure to hand
      transmitted vibration with exposure frequencies 63 Hz, 200 Hz and 500 Hz, and
      levels of acceleration 1 g, 2 g, 4 g and 8 g, fingertip measurements were
      obtained. Temporary threshold shift immediately after the vibratory exposure
      (TTSv,0) was estimated for each exposure from the regression analysis by
      approximation of an exponential function. Time constant (tc) was also estimated
      at the same time by the analysis. The coefficients of determination were large.
      Thus, the fit of the exponential function is very good for each exposure. The tc
      corresponds to the recovering velocity of the temporary shift and implies the
      half-life period of TTSv. These parameters enable us to examine more generally
      the relationships of TTSv to the characteristics of exposure vibration, subject
      and other conditions. On this basis, the estimated TTSv,0 and tc were used to
      examine the dependency of TTSv on the characteristics of the exposure vibration
      and the subject. The most effective frequency under the level of 4 g is thought
      to be between 200 Hz and 500 Hz. TTSv,0 of each subject proportionally increased
      with power of acceleration. The coefficient of determination on regression
      analysis was large. This result enables us to estimate TTSv,0 at an arbitrary
      level of acceleration by use of a regression equation derived from experimental
      data.

PMID- 7806404
TI  - Determining periodontal ligament (PDL) cell vitality from exarticulated teeth
      stored in saline or milk using fluorescein diacetate.
AB  - One of the key factors for obtaining a favourable long-term prognosis in avulsed
      teeth is maintenance of the vitality of the periodontal ligament (PDL) cells.
      Most studies which have examined PDL cell vitality have used neutral red or
      trypan blue as stains. However, these stains have certain inherent disadvantages.
      The purpose of this paper was to (i) evaluate the use of saline and milk as
      storage media for PDL cells and (ii) determine the value of using fluorescein
      diacetate (FDA) as a staining medium for vital PDL cells on the root surface of
      avulsed teeth. Thirty-two single-rooted premolars were utilized from patients
      aged 13 to 28 years. Following atraumatic extraction, the teeth in the
      experimental groups were air dried for 10 min and then placed in either milk or
      saline for 120 min. Both control and experimental teeth were subjected to
      trypsinization procedures, staining with FDA, and haemocytometer readings to
      determine the number of vital cells. There was no statistically significant
      difference in the number of viable cells on the root surfaces of teeth after 2 h
      of storage in either milk or in saline. Furthermore, staining with FDA provided
      an excellent method by which to determine PDL cell vitality.

PMID- 7806405
TI  - Influence of age on the extent of voids in root canals sealed using a cold
      lateral condensation technique.
AB  - The aim of this study was to examine whether it is more difficult to achieve
      complete obturation of the root canal in teeth from different age groups, using
      the measurement of voids within the obturated canal to determine the quality of
      endodontic therapy. One-hundred and fifty-two single-rooted premolar teeth
      extracted from patients of known age were collected. Following cleaning and
      storage the teeth were decoronated and radiographed. Forty selected teeth were
      allocated to one of four age-groups, (under 20, 20-35, 36-50, over 50 years) each
      consisting of 10 teeth. The working length was determined radiographically and
      preparation was carried out using the step-back technique. Each canal was
      obturated using cold lateral condensation with Tubliseal cement. The roots were
      then sectioned longitudinally and photographed. Sections and transparencies were
      subjected to image analysis to determine the total areas of root canal, sealer
      and voids respectively and statistical analysis of the differences between the
      various age groups was undertaken. There was a trend towards a reduction in the
      areas of sealer and sealer plus void with respect to increasing age group,
      although no significant differences existed. A significant relationship (P <
      0.05) was found between the area of voids found in the youngest group when
      compared with all other groups, the greatest cumulative area of voids being found
      in the youngest teeth.

PMID- 7806406
TI  - In vitro efficiency of endodontic irrigation solutions on protein desorption.
AB  - The use of irrigating solutions is widely accepted as a necessary adjunct to
      biomechanical preparation to obtain adequate cleansing of the root canal system.
      In this study, the efficiency of three solutions was tested in an in vitro
      experimental system for the removal of protein from apatite surfaces: Salvizol (a
      bis-dequalinium acetate solution) and sodium hypochlorite at 0.5, 1, 3 and 6% at
      pH 7.4 and 11.5. Buffered Tris-HCl solutions at pH 7.4 and 11.5 were used as
      controls. All chemicals showed rapid kinetics effects since no variation of the
      process could be detected after 5 min. Salvizol was the least efficient solution
      since it induced only a 2% protein desorption. Sodium hypochlorite efficiency
      increased with concentration to reach a 70% protein desorption from the apatite
      surface. In general, alkaline solutions were more efficient than buffered ones,
      and the ionic strength did not appear to have a major effect on the protein
      desorption process.

PMID- 7806407
TI  - Effects of the Flexogates and Canal Master U on root canal configuration in
      simulated curved canals.
AB  - The purpose of this study was to compare the Canal Master U (CMU) instrumentation
      technique with that of a similar instrument, the Flexogates (FG). Forty simulated
      curved canals were divided in two groups of 20 each. One group was prepared using
      the CMU instrumentation technique and the other using the FG technique.
      Comparison was made by measuring the diameter of the prepared canals and
      transportation that occurred at the canal length and at levels 1, 3 and 5 mm
      coronal to the canal length. Data obtained were analysed statistically. Results
      showed that the final diameter of the prepared canals was not significantly
      different between the CMU or the FG. However, the FG transported the outer wall
      of the curvature more than the CMU at the canal length and at 1 mm from the CL.
      Although the difference in the canal transportation was statistically significant
      it may not be of clinical importance.

PMID- 7806408
TI  - Variations in power output of the Piezon-Master 400 ultrasonic endodontic unit.
AB  - The present study was undertaken to see if there was any variability in the power
      output of Piezon-Master 400 ultrasonic files when driven using different
      generators, tranducers and file holders. The displacement amplitude of the
      oscillating tip of the file in air was used as a measure of the power output. The
      results showed that there was considerable variability in the power output of
      Piezon-Master 400 ultrasonic files of similar size and length when driven using
      different generators, transducers and file holders. In consideration of this, it
      is recommended that a calibration device be incorporated in the ultrasonic unit
      so that the operator will have some knowledge of when the unit is working at its
      maximum efficiency.

PMID- 7806409
TI  - A laboratory study of root fillings in teeth obturated by lateral condensation of
      gutta-percha or Thermafil obturators.
AB  - The aim of this in vitro study was to assess the quality of root canal obturation
      and degree of apical dye penetration in teeth root-filled with either laterally
      condensed cold gutta-percha or Thermafil obturators. A total of 144 extracted
      teeth with single roots were included in the study. All canals were prepared with
      a standard technique using a sonic handpiece with copious irrigation. Radiographs
      taken of the teeth to show the maximum degree of canal curvature were then
      exposed and the angle, radius and position of curvature determined. This
      information about the canals, together with their working length and diameter at
      end-point was used to divide the teeth into two experimental and two control
      groups. A total of 71 teeth were filled with Thermafil obturators, 69 with
      lateral condensation while four teeth remained unfilled and acted as controls.
      Following obturation, the teeth were radiographed in two planes and the technical
      quality of fill assessed on a four-point scale. All access cavities were then
      sealed and the teeth immersed in dye for 48 h before being split longitudinally.
      Linear dye penetration via the apical foramen was then assessed. In both straight
      and curved canals obturation with Thermafil obturators was significantly quicker
      (P < 0.001) then lateral condensation. Apical extrusion of gutta-percha occurred
      significantly more often in straight canals obturated with lateral condensation
      (P < 0.005) but there was no difference in curved canals. There was little
      difference in the radiographic quality of fill in the apical halves of the root
      fillings but Thermafil obturators were significantly better in the coronal halves
      when viewed from the proximal.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7806410
TI  - An in-vitro evaluation of the influence of temperature of plasticization on the
      sealing ability of Thermafil.
AB  - The effect of temperature of plasticization on the sealing ability of Thermafil
      obturators was evaluated. Forty-eight canals in roots of extracted human
      mandibular molar teeth were divided into four groups of 12. The root canals had
      curvatures of less than 25 degrees, as determined using the Schneider technique.
      Four canals were used as positive and negative controls. All canals were prepared
      using a step-back technique to size 30 at the working length. Roth's sealer was
      used in all canals. In one group the Thermafil obturators were thermoplasticized
      in an open flame, as recommended by the manufacturer. In the remaining three
      groups the obturators were thermoplasticized by immersion in water-baths
      maintained at constant temperatures of 60, 75 and 90 degrees C respectively.
      After immersion in Indian ink, the teeth were cleared and the depth of
      penetration of dye through the apical foramen was measured. In all specimens
      there was extrusion of sealer and sometimes gutta-percha beyond the apical stop.
      Sometimes, there was leakage up to the apical stop but not beyond. In view of
      this the measurements were divided into leakage from the apical foramen to the
      apical stop and from the apical stop coronally. It was found that in the zone
      between the apical foramen and the apical stop the Thermafil obturators
      plasticized at 60 degrees C produced a significantly better seal than those
      obturators plasticized in an open flame (P < 0.05). In the zone coronal to the
      apical stop there were no significant differences in leakage between the groups.

PMID- 7806411
TI  - The cervical window as an aid in root canal access.
AB  - Access to the coronal opening of root canals may be very difficult in cases where
      cervical caries, whether treated or not, has developed. A direct view through a
      buccal opening, called a buccal window, was successfully used on two patients and
      is proposed for similar cases.

PMID- 7806412
TI  - A clinical evaluation of one and two-appointment root canal therapy using calcium
      hydroxide.
AB  - A clinical study using vital maxillary central incisors was performed to evaluate
      the incidence of postoperative pain after root canal treatment in one- or two
      appointments using a calcium hydroxide-containing root canal sealer. No
      differences were observed between the two groups.

PMID- 7806413
TI  - Clinical reliability of the dentine bridge formed after pulpotomy: a case report.
AB  - An exposed pulp in a crown-fractured vital young tooth may be treated with either
      pulp capping or pulpotomy, using a calcium hydroxide dressing. Calcium hydroxide
      stimulates dentine bridge formation, which is a good indicator of pulp vitality.
      In this case it is reported that, although seriously contaminated for a long
      period with debris from the oral environment, the dentine bridge which formed
      after pulpotomy was able to function as a protective pulpal barrier. The tooth
      responded to an electrical pulp tester within normal limits and the periapical
      radiographic appearance was normal at review after 7 years.

PMID- 7806414
TI  - Low surface tension calcium hydroxide solution is an effective antiseptic.
AB  - The antimicrobial effects of a saturated calcium hydroxide solution, and in
      combination with 10% and 20% detergent, were evaluated on Streptococcus faecalis,
      Streptococcus sanguis, Streptococcus mutans, Streptococcus salivarius, Neisseria
      sp., diphtheroid, Staphylococcus aureus, Lactobacillus sp., Staphylococcus
      epidermidis, Bacillus subtilis and Candida albicans. The saturated calcium
      hydroxide solution was effective against only four of the 11 microorganisms
      studied over a 60-min exposure time. The calcium hydroxide solutions containing
      detergent killed all 11 test organisms over a 30-min exposure time. This
      difference was statistically significant (P < 0.01). No statistically significant
      difference in antimicrobial action was found between the 10% and 20% detergent
      calcium hydroxide solutions (P > 0.01). However, the low surface tension (46.5 x
      10(-3) Nm-1) and high pH (10.8) of the calcium hydroxide solution with 20%
      detergent establish it as the more effective solution.

PMID- 7806415
TI  - Extraosseous calcifications in patients on chronic dialysis.

PMID- 7806416
TI  - Mechanisms of acid-base homeostasis in acetate and bicarbonate dialysis, lactate
      hemofiltration and hemodiafiltration.
AB  - The different mechanisms of acidosis buffering were investigated in 15 RDT
      patients dialyzed in cross-over with four depurative techniques: acetate dialysis
      (AD), bicarbonate dialysis (BD), lactate hemofiltration (LHF) and
      hemodiafiltration (HDF) with acetate bath and lactate reinfusion fluid. Blood pH,
      bicarbonate, blood gases, intraerythrocytic pH - on red cell hemolisates - anion
      gap, L-lactate, pyruvate, adenosinmonophosphate (ADP) and 2-3 Diphosphoglycerate
      (2-3 DPG) levels were evaluated. During AD the intradialytic buffering is
      initially achieved by the CO2 fall and later by the acetate metabolism and an
      important bicarbonate shift from the intra to the extracellular space. A
      physiological compensation is obtained during BD with bicarbonate administration
      and a mild ventilatory response to the pCO2 increase. In LHF the massive lactate
      administration, with plasma levels of 7 mmol/l, strongly alters the Central
      Nervous System elettroneutrality inducing a hyperventilatory response with a
      purely pulmonary acidosis buffering. Furthermore the lactate/pyruvate ratio rose
      as high as 40:1 with ADP increase and cellular energy depletion. In HDF several
      different mechanisms are associated: the CO2 fixation, the acetate muscular
      metabolism, the intra-extracellular bicarbonate shift with the pulmonary response
      driven by lactate Central Nervous System penetration.

PMID- 7806417
TI  - Comparative evaluation of different methods to estimate urea distribution volume
      and generation rate.
AB  - Eight methods to estimate urea distribution volume and generation rate from blood
      urea samples measured in dialysis patients are reviewed. An analytical solution
      has been provided for a double-pool variable volume kinetic model to allow for
      faster and more accurate simulation and identification. The reliable parameter
      estimates provided by the double-pool kinetic model starting from seven samples,
      were assumed as references for the estimates obtained by the remaining methods.
      These include three kinetic models and four methods based on urea mass-balance.
      In particular, the estimation techniques differ in the number of compartments
      where urea is assumed distributed (double- and single-pool) or in the number of
      blood urea samples. Among the methods based on mass-balance, two techniques
      neglecting the weight loss or the urea generation during dialysis, were also
      analysed. The results obtained during hemofiltration sessions using three
      samples, usually available in clinical practice at the beginning and at the end
      of dialysis, demonstrate that a new method based on double-pool kinetics
      provides, on average, the most reliable estimates. Moreover, methods belonging to
      a single pool view and including both weight loss and urea generation during
      dialysis seem to underestimate by 1 divided by 2 liters the urea distribution
      volume. However, neglecting the weight loss or the urea generation can
      overcompensate this error, resulting in a significant overestimation of the
      distribution volume. Finally, it has been experimentally proved that the single
      pool kinetic methods overestimate the urea production rate, while techniques
      based on mass balance provide more reliable values.

PMID- 7806418
TI  - Dialyser reuse: an automated system using peracetic acid.
AB  - For 3 years starting in April 1989, in a 17-station, in-centre haemodialysis unit
      at the Toronto Western Hospital, re-use of dialysers was performed using the
      Renatron-2 Dialyser Reprocessing System with peracetic acid as a sterilant.
      During this period 40,234 treatments were carried out and dialysers were used an
      average of 4.2 times. Net savings, after taking into account the total costs of
      re-use, averaged Can $309,000,000 per year. There were no deaths and no
      discernible morbidity attributable to the practice of re-use. We conclude that
      dialyzer re-use is an effective way to reduce the costs of haemodialysis and is
      entirely safe providing that it is carried out properly.

PMID- 7806419
TI  - Complement activation in dialysis: effects on cytokines, lymphocyte activation
      and beta 2 microglobulin.
AB  - Anaphylatoxins generated by complement activation by filter membranes are present
      in plasma during hemodialysis (HD). In the presence of endotoxins which may
      contaminate the dialysate, they can trigger monocytes to produce interleukin-1
      (IL-1) and tumor necrosis factor (TNF), with detrimental effects for the
      patients. We have investigated whether or not the use of complement activating
      (cuprophan) and non- (or less-) activating membranes (polysulfone,
      polymethylmethacrylate or polyacrylonitrile) per se influences cytokine levels in
      HD patients. Our results indicate that if a sterile bicarbonate solution is used
      as dialysate, there are no significant increases in IL-1, TNF, interleukin-2 (IL
      2) and soluble IL-2 receptors (sIL-2r) throughout HD, even with cuprophan
      membranes. Moreover even a prolonged use of this membrane (three months) did not
      change pre-dialysis levels of cytokines and receptors. Use of complement
      activating membranes also does not influence beta 2 microglobulin levels.

PMID- 7806420
TI  - Endothelialization of cardiac valve bioprostheses.
AB  - The main disadvantage of implanted xenograft valves used in cardiac surgery is
      their poor clinical long-term result, due to early tissue degeneration. In order
      to improve the performance of such glutaraldehyde fixed bioprostheses, a
      biological coating with viable endothelial cells was suggested. Therefore,
      glutaraldehyde preserved bovine pericard patches, as well as commercially
      available xenograft valves, were lined using human venous endothelial cells or
      microvascular cells from the subcutaneous fat tissue. Before cells were
      transplanted into their new environment, grafts were treated with an amino acid
      solution in order to neutralize the cytotoxic effect of free aldehydes, and
      precoated with fibronectin-heparin and basic fibroblast growth factor (bFGF) or
      endothelial cell growth supplement (ECGS) in order to enhance cell proliferation.
      Coated specimens were kept in culture conditions for a further seven days.
      Proliferation of transplanted cells was verified by an increase of activation
      following 3H-thymidine incorporation, while the maintained metabolic cell
      activity was demonstrated via Prostacycline (PGI2) measurement. Morphology was
      evaluated by means of scanning electron microscopy (SEM). As evaluated by the
      beta-Counter, 7 ng/ml bFGF (288,727 +/- 39,668 counts on day 4) substantially
      enhanced cell proliferation after seeding, opposed to the stimulation with 30,000
      ng/ml ECGS (91,924 +/- 1129 counts on day 4), (p < 0.001). The PGI2 release of
      transplanted cells was stimulated with 25 microM Na arachidonic acid by the
      factor 2.6 +/- 0.3 and inhibited with 5 mM acetylsalicylic acid by the factor 0.7
      +/- 0.2 on day 4 when compared with the basic level.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7806421
TI  - Cerebral blood flow velocity during high volume plasmapheresis in fulminant
      hepatic failure.
AB  - High volume plasmapheresis has previously been found to improve neurological
      statuses in patients with fulminant hepatic failure. We investigated the
      relationship between the neurological status and cerebral blood flow velocity
      (Vmean) during high volume plasmapheresis in 18 consecutive patients (ten females
      and eight males) with fulminant hepatic failure, with a mean age of 43 (range 9
      to 57) years. The mean arterial pressure (MAP) and intracranial pressure (ICP)
      were also recorded. A total of 16% of body weight was exchanged with fresh frozen
      plasma per day. Thirty-six plasma exchanges wer performed with a median of 2
      (range 1 to 8) per patient. Eleven of the patients survived (61%), nine after
      liver transplantation. Following the first high volume plasmapheresis, the coma
      score improved from 6 (1-8) to 2 (0-8) (p < 0.05), Vmean increased from 40 (14
      152) to 62 (16-186) cm s-1 (p < 0.05), and MAP from 72 (35-118) to 94 (47-138)
      mmHg (p < 0.05). The intracranial pressure (ICP) was monitored and remained
      unchanged in nine patients whereas the cerebral perfusion pressure (MAP minus
      ICP) increased in the surviving group from 55 (40-74) to 80 (50-91) mmHg (p =
      0.07) in contrast to no changes in the non survival group. In conclusion this
      study suggests that the neurological status, may improve during high volume
      plasmapheresis as MAP and Vmean increase the cerebral oxygen delivery.

PMID- 7806422
TI  - Dialysate calcium loss using a calcium free dialysate.
AB  - Using a dialysate that contained no calcium, we studied the amount of calcium
      lost and the clearances of urea, creatinine, phosphate and calcium in fifteen
      different dialyzers at blood flow/min (QB) of 200 and 300. Five of these
      dialyzers, covering the functional range of the fifteen, were also tested at QB
      of 100, 150 and 400. The collection period was divided into the first twenty
      minutes and the remaining 220 minutes. Clearance was calculated using the initial
      twenty minutes and for all dialyzers the creatinine, phosphate and calcium
      clearances were linearly related to the measured urea clearance, r = 0.946, 0.810
      and 0.808 respectively. Calcium recovered in the dialysate varied, depending on
      the dialyzer and QB, however the amount found plateaued at QB 200 and did not
      increase further, unlike creatinine, phosphate and urea. Total dialysate calcium
      loss for a four-hour dialysis averaged 49.9 mmol (range 42.2-63) or almost 2g of
      elemental calcium for QB of 200 ml/min and 48.9 mmol (range 31.1-65.5) or 1.95 g
      of elemental calcium for a QB of 300 ml/min. Decreasing the calcium infusion
      replacement rate did not decrease the calcium dialysate loss in equal amounts as
      the blood to dialysate gradient falls leading to a smaller than expected
      dialysate loss. Measured urea clearance in these fifteen dialyzers was
      approximately 20% less than specified by the manufacturer and almost 30% less for
      creatinine and phosphate. This difference is probably due to in vivo measurements
      with blood whereas most of the specifications are obtained using saline in
      vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7806423
TI  - Determinants of drug removal by continuous hemofiltration.
AB  - Continuous hemofiltration was conducted in vitro to identify parameters that
      affect drug transport across hemofilter membranes. The removal of seven drugs
      with different molecular weights and protein binding characteristics was
      assessed. Sieving coefficients were determined with both blood and saline using
      polysulfone, polyacrylonitrile and polyamide membranes. Drug sieving coefficients
      obtained with saline were generally higher than those obtained with blood.
      Molecular weights of the drugs did not correlate with the magnitude of drug
      sieving. Sieving coefficients in blood were also predicted from saline data
      assuming plasma protein binding is responsible for the reduced drug sieving with
      blood. For drugs that are highly protein bound, protein binding was the primary
      factor limiting drug sieving. Presence of plasma proteins also had a modest
      effect on sieving of other drugs. The sieving coefficients obtained with the
      polyacrylonitrile membrane tend to be different from those obtained with the
      other hemofilters. Drug-membrane interaction may contribute to the differences in
      drug transport among the membranes.

PMID- 7806424
TI  - Double pass dialysis: a new method of renal replacement in patients with
      malfunctioning vascular access.
AB  - Several patients undergoing chronic renal replacement therapy present problems
      related to their vascular access. Low blood flows and high rates of recirculation
      are common in such patients in which, for this reason, it becomes difficult to
      apply highly efficient techniques or techniques where diffusion and convection
      are combined as in hemodiafiltration. In these patients we studied the
      possibility of partially recirculating the blood in the extracorporeal circuit in
      order to increase the flow rate per single hollow fiber; we defined our system
      "double pass dialysis". We evaluated the system's efficiency in 12 patients
      during 24 dialysis sessions: 12 high flux dialysis sessions (without reinfusion)
      and 12 hemodiafiltration sessions (9 liters reinfusion). Different surfaces of
      polyacrylonitrile dialyzers were utilized (1.3-1.7-2.1 sqm) at 250 and 350 ml/min
      of blood flow with or without 100 ml/min of recirculation. During each dialysis
      session blood and dialysate samples were taken in order to calculate BUN,
      Creatinine, Phosphate and Inuline clearances from both the blood and dialysate
      side. The clearances of low molecular weight solutes were not really influenced
      by the artificial increase of the blood flow, but on the other hand, the
      clearances of higher molecular weight solutes increased from 10 to 30% during
      both high flux dialysis and hemodiafiltration with recirculation. This increase
      was evident mostly in hemodiafiltration suggesting that the cleaning effect on
      the membrane has a positive impact on the permeability. The good clinical results
      obtained with the double pass dialysis show that the system is safe and reliable
      and may become a valid support in critical situations in order to reach adequate
      dialysis treatment.

PMID- 7806425
TI  - Cellulose-ester as membrane materials for hemodialysis.
AB  - The majority of dialysis membranes are fabricated from regenerated unmodified
      cellulose. This standard type of cellulosic membrane is frequently under attack
      because of its alleged lack of biocompatibility. Recent developments, however,
      have proven that a chemical modification of the reactive surface groups of
      regenerated cellulose, the hydroxyl-groups, limits the complement-activating
      potential of these materials and thus improves its blood-compatibility. We
      extended the idea of modifying cellulose for improved blood-compatibility to a
      series of different cellulose esters. Special focus was directed towards the
      question whether a variation of the type of substituent and degree of
      substitution could influence the blood-compatibility pattern of these materials:
      the analysis of blood-compatibility profiles showed a direct dependency on the
      type of substituent and the degree of substitution (DS). As an example, it was
      found that the DS, necessary for a complete reduction of complement activation,
      decreases with increasing chain lengths of aliphatic substituents. Optimal
      degrees of substitution are characteristic of the type of substituents and enable
      us to tailor materials specifically for optimized blood compatibility.

PMID- 7806426
TI  - Long-term comparative evaluation of synthetic and cellulosic membranes in
      dialysis.
AB  - A long-term retrospective evaluation (5 years) compares two groups of RDT
      patients (group 1 on continuous treatment with cellulosic membranes and group 2
      with synthetic membranes) regarding survival, general clinical morbidity, and
      beta 2M-related morbidity. The results showed no significant long-term
      differences between the groups either for survival or general morbidity despite
      some differences in biocompatibility. The higher intradialytic removal of beta 2M
      by synthetic membranes did not lead to a reduction in either pre-dialysis beta 2M
      values or beta 2M related morbidity. The higher cost of synthetic over cellulosic
      membranes and the disappointing of many clinical expectations suggest that the
      use of such membranes, in association with alternative techniques, should take
      place only according to certain "elective" indications such as old age, diabetes,
      vascular instability or intradialytic disequilibrium syndrome.

PMID- 7806427
TI  - An in vitro physiologic model for cardiopulmonary simulation: a system for ECMO
      training.
AB  - Extracorporeal life support (ELS) systems may be run by certified perfusionists,
      specially trained nurses or respiratory therapy staff. Guidelines for the
      training, certification and retraining of ELS operators have been established by
      the Extracorporeal Life Support Organization. Recommendations include "... a well
      defined program for staff training, certification, and retraining". Some
      clinicians have suggested that ELS operators be certified and recertified in an
      animal laboratory. But such practice involves veterinary expenses, animal use
      issues and considerable clean-up and disposal. We describe an alternative method
      of training, using an in vitro physiologic model designed to simulate various
      pathophysiologic states. In addition, the in vitro physiologic model may be used
      to evaluate membrane lung characteristics. This model's ease of construction,
      maintenance and use for training compared with live animal techniques are
      discussed. Research capabilities may be more flexible than with the use of the
      live animal technique. The in vitro physiologic model can be a useful and
      convenient asset to an extracorporeal membrane oxygenation/extracorporeal carbon
      dioxide removal (ECMO/ECCO2R) program.

PMID- 7806428
TI  - Biomechanical tissue properties as an indicator of organ vitality prior to
      transplantations.
AB  - An organ's vitality prior to transplantation can be evaluated by analysis of its
      mechanical properties. A new apparatus was designed to measure these properties.
      The organ to be tested is placed in a reservoir with saline and submitted to the
      load of a cylindrical element. The load is applied in a stepwise mode and results
      in a small local deformation of the organ. This deformation is identical to the
      displacement of the cylinder and is measured as a function of time. This is
      compared to a theoretical analysis of the deformation of a viscoelastic
      halfspace. This theory was used to interpret the results of experiments which
      were carried out on eight rabbit kidneys. The instantaneous modulus of elasticity
      reaches a maximum within 15 minutes, then decreases and reaches a steady state
      after 30 minutes of warm ischemia. The method is easy to apply and appears to be
      useful for the quantification of an organ's vitality and in particular recognizes
      the level of the organ's edema before transplantation.

PMID- 7806429
TI  - T-cell adjuvants.
AB  - T-cell adjuvancy involves the use of agents to stimulate preferentially delayed
      type hypersensitivity (DTH). Traditional adjuvants like Alum, Freunds, muramyl
      peptides, and endotoxins are not selective. Natural infection (e.g. vaccinia) may
      yield selective DTH. Low dose cyclophosphamide (CY) with mycobacteria was the
      first experimental T-cell adjuvant. New adjuvant formulations (ISCOMS, MAPS,
      etc.) with synthetic T-cell epitopes offer improved formulations. Upregulation of
      TH-1 helper cells and their actions with interleukins like IL-2, IL-12, and gamma
      IFN or antibodies to IL-4 and IL-10 may augment potently pathogen and tumor
      resistance. Similarly, transfection of tumor target cells with genes for IL-2, IL
      12, gamma IFN, etc., offers novel vaccine treatment approaches. Finally,
      "thymomimetic" peptides like thymosin alpha 1 or drugs like levamisole or
      isoprinosine alone or in conjunction with interleukins may augment TH-1 and DTH
      responses. These approaches are seeing increasing emphasis in new treatment
      strategies for cancer and infections like HIV.

PMID- 7806430
TI  - Pentoxifylline inhibits tumor necrosis factor-alpha-mediated cytotoxicity and
      cytostasis in L929 murine fibrosarcoma cells.
AB  - Tumor necrosis factor-alpha (TNF alpha) is recognized as a principal mediator of
      a variety of inflammatory conditions. In animal models, pentoxifylline attenuates
      the morbidity and mortality of bacterial sepsis, an effect which has been
      attributed to its ability to suppress the induction of TNF alpha. To determine
      whether pentoxifylline also directly inhibits the effects of TNF alpha, the
      ability to inhibit cytotoxicity on the TNF alpha-sensitive murine fibrosarcoma
      cell line, L929, was examined. Cell viability was assessed by crystal violet
      staining and cell proliferation was assessed by [3H]-thymidine uptake assay. TNF
      alpha induced dose-dependent cytotoxicity. At concentrations of TNF alpha of 1000
      U/ml, viability at 3 days was approximately 35% of control. When L929 cells were
      co-incubated with TNF alpha (1000 U/ml) and pentoxifylline (1 mM), cell viability
      increased to approximately 75% of control (P = 0.001). At concentrations of TNF
      alpha of 10,000 U/ml, cell viability which was 11% of control with TNF alpha
      alone increased to 53% in the presence of pentoxifylline (P = 0.002). TNF alpha
      at 1000 and 10,000 U/ml concentrations decreased [3H]-thymidine uptake to
      approximately 5% of control values. Co-incubation with pentoxifylline
      significantly increased uptake to 13% of control at both TNF alpha concentrations
      (P = 0.002). Pentoxifylline did not affect the level of type I TNF alpha receptor
      -ligand cross-link product. However, in TNF alpha receptor binding assays,
      incubation with pentoxifylline 1 mM for 4 h was associated with an increase in
      the receptor affinity (control: KD = 0.42 nM vs pentoxifylline-treated: KD = 0.21
      nM, P = 0.006), without significant change in number of type I TNF alpha
      receptors, suggesting that pentoxifylline affects post-receptor signalling
      events. We have observed that pentoxifylline prevents the TNF alpha-mediated
      activation of sn-2 arachidonic acid-specific cytosolic phospholipase A2, an
      important component of the signal transduction pathway of TNF alpha cytotoxicity.
      Because pentoxifylline does not inhibit all activities mediated by the type I TNF
      alpha receptor, its selective inhibition of post-receptor signalling may
      facilitate further study into the mechanisms underlying the diverse effects of
      TNF alpha.

PMID- 7806431
TI  - Effect of histamine in autoimmune myocarditis mice.
AB  - The contractile effect of histamine, as well as the H1 receptor population and H2
      receptor-mediated cAMP production, were measured in cardiac tissue from control
      normal and autoimmune myocarditis mice. Histamine triggered positive chronotropy
      and negative inotropy at high concentrations in both control and autoimmune
      auricles, H2 receptors being the most important mediator of these responses. In
      contrast, in atria from autoimmune myocarditis mice, histamine at lower
      concentrations caused positive inotropy and negative chronotropy. These effects,
      not verified in the normal control atria, are mediated by H1 receptors. The
      expression of H2 and H1 receptors mediating the cardiac response to histamine was
      evaluated through histamine-stimulated cAMP level and binding of [3H]
      mephyramine, respectively. Both control and autoimmune myocardium were able to
      increase cAMP levels, an effect that was inhibited by H2 antagonist drug. The
      amount of cAMP was significantly higher in control myocardium than in those from
      autoimmune ones. Saturable binding of [3H] mephyramine occurs in autoimmune
      myocardium, with distinct high and low affinity binding sites. In control
      myocardium non-saturable binding was detected. These results suggest that H1 and
      H2 receptors coexist in heart from autoimmune myocarditis mice, whereas only H2
      receptors are present in myocardium from control mice. The presence of H1
      receptors in autoimmune myocardium could be an important factor in the regulation
      of its physiological behaviour.

PMID- 7806432
TI  - Factors involved in the down-regulation of cytochrome P450 during Listeria
      monocytogenes infection.
AB  - The activation of host defense mechanisms has been shown to cause a depression in
      hepatic cytochrome P450-mediated metabolism in rodents and humans. In a previous
      study, it was demonstrated that the Gram-positive bacteria Listeria monocytogenes
      causes a down-regulation of hepatic cytochrome P450 and related substrate
      metabolism as a result of a pretranslational depression of apoprotein synthesis.
      The objectives of this study were to determine whether the effect of listeria on
      hepatocyte cytochrome P450 involves hepatic nonparenchymal cells and whether the
      hemolysin, secreted only by hemolytic forms of the bacteria, plays any part in
      mediating this effect. Total cytochrome P450 levels as well as ethoxyresorufin-O
      dealkylase (EROD) and benzyloxyresorufin-O-dealkylase (BROD) activities were
      significantly reduced in hepatic microsomes isolated from mice infected in vivo
      for 48 h with 15U listeria, whereas the same dose of the avirulent non-hemolytic
      M3D strain had no effect. Listeria (15U) significantly depressed hepatocyte EROD
      and BROD activities after 24 h incubations with liver cell cultures containing
      hepatocytes and nonparenchymal cells, as the result of both a direct effect on
      the hepatocyte and an interaction of listeria with hepatic nonparenchymal cells.
      The M3D strain of listeria had no effect on cytochrome P-450-mediated metabolism
      in isolated cells, confirming that hemolysin is an essential component of the
      mechanism responsible for the down-regulation of cytochrome P450 during listeria
      infections.

PMID- 7806434
TI  - Lectin-activated killer cells rapidly induced by pokeweed mitogen conjugated
      beads and their in vivo antitumor effects.
AB  - Pokeweed mitogen (PWM) was found to induce rapidly killer cells in human
      peripheral blood mononuclear cells (PBMC). To avoid PWM contamination in infused
      lymphocytes, PBMC were stimulated with PWM-coated beads, CMC-1. One hour of
      stimulation with CMC-1 led to distinct cytotoxic activity in PBMC at 7 h, this
      reaching a peak at 23 h in the following in vitro culture. The cytotoxic activity
      and target cell spectrum of CMC-1-activated killer (PWM-AK) cells were similar to
      those of lymphokine-activated killer (LAK) cells, the precursor cells of PWM-AK
      cells, as are those of LAK cells which are also low-density lymphocytes. The in
      vivo antitumor effects of PWM-AK cells were examined in nude mice with peritoneal
      carcinomatosis generated by the human colon cancer cell line, RPMI 4788. The
      intraperitoneal (i.p.) injection of PWM-AK cells immediately after stimulation
      with CMC-1 significantly prolonged the survival of tumor-bearing mice, suggesting
      that these cells could be of value for clinical cancer therapy.

PMID- 7806433
TI  - Glutathione increases interleukin-2 production in human lymphocytes.
AB  - It is known that glutathione (GSH) has an immunological effect on several
      features of the immune system. The present study investigated the effects of GSH
      on interleukin-2 (IL-2) production from normal human peripheral blood lymphocytes
      (PBL). The results showed that both exogenous GSH and 2-mercaptoethanol (2-ME)
      significantly increased intracellular GSH levels after PBL were incubated with
      both agents. IL-2 production from PBL was markedly increased at the presence of
      exogenous GSH (0.5-8 mmol/l) or 2-ME (12.5-50 mumol/l) which corresponded to 1.57
      2.82 nmol/10(6) cells and 1.41 - 1.80 nmol/10(6) cells of intracellular
      concentrations of GSH, respectively. However, IL-2 production seemed to reach a
      steady level when exogenous GSH concentrations in cell culture were between 2 and
      8 mmol/l. The findings also showed that there was a positive correlation between
      the IL-2 concentrations and intracellular GSH levels. This study indicated that
      both exogenous GSH and 2-ME were able to elevate intracellular GSH levels and the
      increased intracellular GSH could increase IL-2 production in vitro. It is
      suggested that GSH may exert its effects on the immune system via the regulation
      of IL-2 synthesis.

PMID- 7806435
TI  - Effect of ouabain on lymphokine-activated killer cells.
AB  - A large amount of evidence points towards the potential role of lymphokine
      activated killer (LAK) cells as tools in the treatment of chronically stressed
      conditions, such as cancer. The modulation of this activity by biologically
      active endogenous compounds of the HPA (hypothalamic-pituitary-adrenal) axis,
      however, is not completely understood. Ouabain, a specific inhibitor of Na(+)
      K(+)-ATPase, and now recognized as an endogenous component present in human
      plasma, was tested on IL-2 and TPA-activated killer cells. Ouabain was able to
      inhibit the generation of LAK activity, as well as to suppress either PHA or TPA
      induced lymphocyte proliferation. Once the cells were triggered for cytotoxicity,
      however, ouabain was not able to interfere with their effector phase, as it did
      not show any effect when present only during the assay. TPA-induced "LAK-simile"
      cells displayed the same sensitivity towards ouabain as LAK cells did. Although
      the physiological relevance of endogenous ouabain secretion remains elusive,
      these effects of ouabain on LAK cytotoxicity should be considered in patients
      undergoing this kind of immunotherapy.

PMID- 7806436
TI  - Effects of PGE2 upon differentiation and programmed cell death of suspension
      cultured CD4-CD8- thymocytes.
AB  - Recently, several works have focused on the modulation of the immune response by
      arachidonic acid metabolites. Some of these metabolites, such as prostaglandins,
      have been shown to influence thymocyte "education" in vitro. However, the effect
      of one of them, prostaglandin E2 (PGE2), in the education of CD4-CD8- double
      negative immature thymocytes (DN cells) remained unclear. Using a flow cytometry
      analysis of DN cells cultured for 24 h in the presence of PGE2, we observed,
      compared with DN thymocytes cultured without PGE2, an increase in the CD4+CD8-CD3
      immature thymocytes and in the CD4+CD8- and CD8+CD4- mature single positive
      thymocytes and a decrease in the DN and CD4highCD8high double positive
      thymocytes. Other differentiation thymocyte surface markers, such as CD3, CD5,
      TCR alpha beta, TCR delta gamma and HSAg, revealed an increasing number of
      thymocytes bearing these first four markers and a lower expression of the HSAg.
      Furthermore, we observed an accumulation of CD4lowCD8low thymocytes and an
      increasing proportion of hypodiploid nuclei. These two findings have been shown
      to be markers of the programmed cell death process. These findings suggest that
      PGE2 probably acts on thymocyte differentiation through at least two distinct
      pathways. On the one hand, PGE2 seems to promote differentiation of DN cells into
      CD4+CD8-CD3- immature cells and drive CD4+CD8+CD3+ thymocyte to a CD4+CD8- and
      CD8+CD4- mature phenotype. On the other hand, PGE2 is probably implicated
      directly or indirectly in the increase or the acceleration of the programmed cell
      death process of immature CD4+CD8+CD3+ thymocytes, which is linked to the
      positive and/or negative selection.

PMID- 7806437
TI  - "Biddy Early and the CAT scan: art and science".

PMID- 7806438
TI  - Ascorbate and malondialdehyde in stroke patients.
AB  - It is believed that free radical formation and subsequent oxidative damage in the
      form of lipid peroxidation may be a factor in the cerebral damage secondary to
      the ischaemia of a cerebrovascular accident (CVA). Total serum ascorbate and
      malondialdehyde (MDA) were measured in 45 patients with CVA on the day of
      admission to hospital (Time 0) and 48 hours later (Time 48 hours) and also in 45
      age and sex matched controls. There was no statistical difference in total serum
      ascorbate between the control group (34.2 mumol/l +/- 3.1, mean +/- SEM) and the
      CVA patients at Time 0 (37.3 +/- 2.9) but there was a statistically significant
      decrease at Time 48 hours (22.7 +/- 2.0) (p < 0.001) in the CVA patients. With
      MDA there was no statistical difference between the patients at Time 0 (0.79
      mumol/l +/- 0.06) and the control group (0.83 +/- 0.06) but there was a
      significant increase at Time 48 hours (1.65 +/- 0.08) (p < 0.001). These findings
      are in keeping with possible evidence of free radical damage in CVA.

PMID- 7806439
TI  - An association between sputum eosinophilia and carcinoma of the lung: a study of
      549 patients.
AB  - A prospective 11 year study of sputum cytology in 5,475 patients with respiratory
      diseases other than asthma or Loeffler's syndrome showed that carcinoma of the
      lung was the commonest single condition associated with a sputum eosinophilia: it
      occurred in 68 (12.4%) of the 549 patients with pulmonary carcinoma. While
      clearly not a diagnostic finding, sputum eosinophilia should stimulate, in
      appropriate cases, a further search for carcinoma. The cause or causes of the
      eosinophilia are not known at present but the body's reaction to malignancy is a
      topical subject of study worldwide.

PMID- 7806440
TI  - Isolated pulmonary valve endocarditis: a rare or an underdiagnosed disease?
AB  - A 48 year old patient with resistant coeliac disease developed prolonged
      unexplained pyrexia after surgery for small bowel volvulus. Despite extensive
      investigations and intensive antibiotic therapy, he deteriorated and died eight
      weeks postoperatively and significant isolated pulmonary valve endocarditis was
      discovered at autopsy. This diagnosis should be considered in all critically ill
      patients with unexplained pyrexia even in the absence of clinical features of
      endocarditis and transoesophageal echocardiography performed to exclude or
      confirm this lesion.

PMID- 7806441
TI  - Complications and cardiovascular risk factors in insulin-dependent diabetes-
      findings in an Irish clinic and in other European centres.
AB  - The Eurodiab Insulin Dependent Diabetes (IDDM) Complications Study was a cross
      sectional investigation of a stratified random sample of IDDM patients attending
      31 clinics in 16 European countries. We compared the findings in the only
      participating Irish centre (Cork Regional Hospital) with those of the study group
      as a whole. There were fewer episodes of ketosis but severe hypoglycaemia
      occurred more frequently in Cork patients, when compared to the full study group.
      There were no significant differences in the prevalence of background
      retinopathy, proliferative retinopathy, microalbuminuria, macroalbuminuria or
      peripheral neuropathy, when the two groups were compared. However, autonomic
      neuropathy was significantly less common in Cork. The prevalence of
      cardiovascular disease was slightly lower than the Eurodiab average in Cork
      patients, and cardiovascular risk factors were more favourable. Waist-hip ratio
      and total plasma cholesterol were significantly lower than in the full study
      group. The prevalence of hypertension was similar, but there were fewer smokers
      in Cork than in most other centres.

PMID- 7806442
TI  - Leiomyosarcoma of the upper oesophagus--a difficult pre-operative diagnosis.
AB  - The case of a 62 year old female with a leiomyosarcoma of the upper oesophagus is
      described. A pharyngolaryngo-oesophagectomy was performed for adequate excision
      of the tumour. Included is a discussion on the management of leiomyosarcoma of
      the upper aerodigestive tract.

PMID- 7806444
TI  - Report from the World and European Cardiology Congress, Berlin, September 1994.

PMID- 7806443
TI  - Hepatitis C updated.

PMID- 7806445
TI  - Sylvester O'Halloran Surgical Scientific Meeting. March 11-12, 1994. Abstracts.

PMID- 7806446
TI  - Physiological indices of visual fatigue due to VDT operation: pupillary reflexes
      and accommodative responses.
AB  - In spite of the clarification of some significant physiological factors of visual
      fatigue caused by VDT work, pupillary reflexes have not been studied as to how
      they are affected after prolonged visual work. This study examined visual
      function changes objectively in terms of pupillary reflexes and lens
      accommodative responses after a 4-hr VDT operation task. The relationship between
      the two functions was also examined. Two measurements in this paper revealed the
      physiological function changes due to VDT operation. The subjects involved were
      five students with an average age of 22.6 years. First, near-reflex measurement
      ascertained decreases in amplitude and the velocity of accommodation function
      after the visual task. Second, light-reflex measurement revealed a delay of the
      reflex, an increase in the amplitude of the reflex, and a decrease in pupil size
      after the visual task. A weak correlation between the decrease in pupil size and
      accommodation function was found. The occurrence of visual fatigue due to 4-hr
      VDT operation was also confirmed by CFF measurements and reported subjective
      visual symptoms in this experiment.

PMID- 7806447
TI  - Blood and urinary levels of metals (Pb, Cr, Cd, Mn, Sb, Co and Cu) in cloisonne
      workers.
AB  - Blood and urine samples from cloisonne ware workers were assayed for Pb, Cr, Cd,
      Mn, Sb, Co and Cu for biological monitoring. Mean blood Pb levels were 47.8 +/-
      27.3 micrograms/dl (111-13.3 micrograms/dl) for 49 cloisonne glaze workers, and
      0.97 +/- 0.47 microgram/dl (2.4-0.6 microgram/dl) for 62 normal subjects. There
      was a distinct difference between the 2 groups, and slight differences (p < 0.01)
      in mean Cr, Cd and Mn levels. There was a distinct difference in mean urinary Pb
      level between the 2 groups, and slight differences (p < 0.01) in mean Cr, Cd and
      Mn levels. The correlation coefficient, r, between blood Pb and Cd levels was
      0.631 (p < 0.01) for 132 subjects consisting of cloisonne ware workers and normal
      subjects. r between blood Pb and blood Cr levels was 0.501 (p < 0.01), and that
      between blood and urinary Pb levels, 0.794 (p < 0.01). The above assays showed
      that glaze workers at cloisonne plants suffer severe exposure to lead and slight
      exposure to Cd and Cr.

PMID- 7806448
TI  - Aerobic capacity of the brick-field workers in eastern India.
AB  - Forty two male brick-field workers of two age groups, viz. 20-29 and 30-39 yrs
      were studied with a view to determine their aerobic capacity (VO2 max). The
      average values of VO2 max in l.min-1 showed only small change between the young
      and the aged groups, but the values of the VO2 max in ml.kg.-1min-1 showed
      significant difference between the groups due to body weight increase in the aged
      group. The aerobic capacity of the workers engaged in heavy manual work such as
      puddlers and load carriers were found to be comparatively higher and a positive
      significant relationship has been established between the aerobic capacity and
      different occupations in the brick-field workers.

PMID- 7806449
TI  - Determination of delta-aminolevulinic acid in plasma using high-performance
      liquid chromatography: a sensitive indicator of lead effects.
AB  - We developed a simple and reliable method for determining delta-aminolevulinic
      acid (ALA) in plasma (ALA-P) by fluorometric high-performance liquid
      chromatography. The method was applicable to 100 microliters of plasma and the
      mean +/- standard deviation for analytical recovery was 100.4 +/- 2.6% when 50
      micrograms/l of ALA was added to 14 plasma samples. The detection limit for ALA-P
      was 2.0 micrograms/l (signal-to-noise ratio was 5) and the standard curve was
      linear in a wide range up to 400 micrograms/l. The ALA-P level for 26 unexposed
      male adults was 8.6 +/- 1.3 micrograms/l. In 72 male lead workers, logarithm of
      ALA-P concentration was significantly correlated with blood lead concentrations
      (Pb-B) of 2.5-115.4 micrograms/dl (r = 0.924, p < 0.001). Even at the Pb-B level
      less than 15 micrograms/dl, significant linear relationships were found between
      Pb-B and log ALA-P (r = 0.632, p < 0.01), between Pb-B and delta-aminolevulinic
      acid dehydratase activity (ALA-D) (r = -0.573, p < 0.05), and between ALA-D and
      ALA-P (r = -0.765, p < 0.001). It is suggested that ALA-P determined by the
      present method is a useful indicator of biological effects of lead, especially in
      the wide range of Pb-B level.

PMID- 7806450
TI  - Absence of mutagenicity in peripheral lymphocytes of workers occupationally
      exposed to methyl methacrylate.
AB  - Chromosome aberration rates and sister chromatid exchange frequency were examined
      in the peripheral lymphocytes of 38 male workers who were engaged in organic
      glass production and exposed to methyl methacrylate (MMA) vapors at the
      concentrations of 0.9 ppm to 71.9 ppm. The results were compared with the
      findings in the concurrent nonexposed male subjects. Comparison of the exposed
      group with the nonexposed controls showed that there were no exposure-related
      changes in chromosome aberration rate. SCE frequency was higher in the exposed
      group than in the controls, but this was considered to be due to higher ages of
      the former group than that of the latter. In fact, selection of nonsmokers and
      further classification of the exposed nonsmokers into two groups of those with
      exposure below and above a median MMA concentration (ca. 4 ppm) failed to show
      any difference among the three nonsmoking groups in cytogenetic parameters, or
      any dose-dependency. The present results, although in a limited number of
      subjects, indicate that occupational methyl methacrylate exposure under the
      conditions studied is not associated with mutagenicity. This conclusion confirms
      the absence of mutagenicity of methyl methacrylate in humans, and is in general
      agreement with a majority of the results of studies on mutagenicity in vitro,
      animal carcinogenicity and occupational cancer epidemiology of methyl
      methacrylate.

PMID- 7806451
TI  - Osteopathic medical education adapts to a changing environment.

PMID- 7806452
TI  - History of osteopathic medical education accreditation.

PMID- 7806453
TI  - Undergraduate osteopathic medical education.

PMID- 7806454
TI  - Overview of financial assistance resources for osteopathic medical students.

PMID- 7806455
TI  - Income and expenditures of osteopathic medical colleges.

PMID- 7806456
TI  - Osteopathic graduate medical education. Division of Postdoctoral Training of the
      American Osteopathic Association.

PMID- 7806457
TI  - Research programs of the AOA and their role in osteopathic medical education.

PMID- 7806458
TI  - AOA continuing medical education.

PMID- 7806460
TI  - Colleges of Osteopathic Medicine.

PMID- 7806459
TI  - Membership of AOA Committees on Osteopathic Medical Education 1994-1995.

PMID- 7806461
TI  - The danger of complacency.

PMID- 7806462
TI  - Healthcare reform and practice choices: a survey of osteopathic medical students.
AB  - Medical students are major stakeholders in the changing world of healthcare.
      Initiatives to change the specialty makeup and geographic distribution of the
      physician workforce, changes in the organization of healthcare delivery systems,
      and financing systems for healthcare will profoundly alter their practice
      environment while they are in school and just beginning to make career decisions.
      The decisions of osteopathic medical students, who currently make up 30% of the
      profession, will shape the profession's response to the new initiatives and
      determine its place in emerging healthcare systems. The authors surveyed first-
      and second-year osteopathic medical students to ascertain their perceived
      knowledge, opinions, and intentions as they relate to healthcare reform. They
      discovered that increasing numbers of students intend to practice in primary care
      fields. The student respondents support some of the major changes proposed by
      reformers in greater numbers than physicians as a whole, and have different
      priorities that they would like to see addressed in reform. This study reveals
      links between respondents' intentions to practice primary care and support for
      specific reform items, but the results show no link between anticipated
      indebtedness and respondents' intentions to enter primary care or specialty
      fields. The authors conclude that healthcare reform, although still in debate,
      has already exerted an influence on the decision-making processes of medical
      students.

PMID- 7806463
TI  - Somatosensory evoked potentials modification related to isometric voluntary
      contraction.
AB  - Somatosensory evoked potentials were elicited by applying an electrical stimulus
      to the median nerve while the subjects performed a handgrip isometric
      contraction. Somatosensory evoked potentials (SEPs) were recorded from scalp
      positions C3 + 2 and C3-2. SEPs during the increase phase and decrease phase of
      force, and during the hold phase (period of maintenance of steady force) of
      isometric contraction were compared with potentials during rest. SEPs during the
      three phases of isometric contraction were also compared. Changes in SEP
      latencies were not observed. The increase or decrease phase of force and the hold
      phase caused suppression of the relatively late N55-P100 component when compared
      to rest. There was no difference in the amplitude of SEPs during the increase or
      decrease phase. During the hold phase the early N20-P30 component was increased
      when compared to the other two phases. The selective changes of SEPs during the
      three phases of isometric-anisotonic contraction suggested task dependence of the
      gating process.

PMID- 7806464
TI  - Mental challenge elicits "additional" increases in heart rate during low and
      moderate intensity cycling.
AB  - The combined effects of exercise and mental challenge on heart rate (HR) and T
      wave amplitude (TWA) were studied. Twenty male students cycled at low (40% of
      their relative maximal HR reserve (MHRR), for 15 min) and medium (60% MHRR, for
      10 min) intensity exercise workloads. Subjects performed a series of mental
      arithmetic problems for one minute each time: two min before cycling, 10 min into
      low intensity cycling, 10 min into medium intensity cycling, and two and 20 min,
      respectively, after cycling. During both exercise workloads, the mental
      arithmetic elicited significant additional increases in HR. Although TWA
      decreased in response to mental arithmetic at rest, no changes in TWA were
      observed in response to mental task during exercise. However, TWA increased
      significantly following the mental challenge. These results suggest that even a
      mild mental challenge is capable of inducing further changes in the autonomic
      response during low and moderate exercise.

PMID- 7806465
TI  - P300 assessment of anxiety effects on processing novel stimuli.
AB  - In the present experiment, event-related potentials (ERPs) were used to
      investigate the effect of anxiety on the attention to novel stimuli. A total of
      16 healthy subjects participated in an experiment involving the anticipation of
      electric shocks. ERPs from 15 scalp sites were recorded in response to three
      types of auditory stimuli, and two attentional modes during threat and safe
      conditions. The three types of auditory stimuli were (1) frequent "standard"
      tones, (2) rare "target" tones, and (3) rare "novel" sounds. In the passive
      attentional mode, subjects passively listened to the stimuli. In the active
      attentional model, they had to Press a button in response to target tones. In
      each attentional mode, stimuli were presented under two conditions: threat
      (anticipation of shock) and safe (no-shock anticipation). P3 to the target
      stimuli was not affected by shock anticipation. The amplitude of P3 to the novel
      stimuli, however, was increased by the threat of shock in the passive but not in
      the active mode. The lack of impact of anxiety on P3 to the novel stimuli in the
      active mode is discussed.

PMID- 7806467
TI  - Hemodynamic stress responses in men and women examined as a function of female
      menstrual cycle phase.
AB  - Fifteen men and 11 normally ovulating women were each tested twice for
      cardiovascular stress reactivity, cognitive/behavioral performance, and mood
      during a variety of stressors. Each women was tested during both the follicular
      and luteal phase of her menstrual cycle, with men matched for number of days
      between testing. Although the genders did not differ in blood pressure reactivity
      during either phase of the cycle, during both phases of the menstrual cycle women
      exhibited greater heart rate reactivity and tended towards greater cardiac index
      increases, greater pre-ejection period decreases, and lesser vascular tone
      relative to men. Additionally, the menstrual cycle was observed to influence
      gender differences in stroke volume index responses. Specifically, stroke volume
      index responses for women were significantly greater in their luteal versus
      follicular phase resulting in a marginally significant pattern whereby women's
      stroke volume index responses were greater than men's luteally but less than
      men's follicularly. Men and women also differed in cognitive performance and mood
      assessment during the tasks, but the majority of these differences were
      unaffected by the menstrual cycle.

PMID- 7806466
TI  - Auditory ERPs to non-target stimuli in schizophrenia: relationship to
      probability, task-demands, and target ERPs.
AB  - The effects of task demands and stimulus probability on the N1 and P2 components
      of the auditory event-related potential (ERP) to non-target stimuli were
      investigated in normal and medicated schizophrenic subjects. Subjects either read
      a book while tones were presented, or counted the rare (low probability) tones in
      an auditory oddball paradigm. The mismatch negativity to rare tones in the
      reading condition was present, and did not differ between groups. N1 amplitude
      was smaller in schizophrenic patients in all conditions. When subjects counted
      the rare tones, the amplitude and latency of P2 increased. This task-related
      effect on P2 was much greater in control than in schizophrenic subjects.
      Difference ERPs were used to better characterize the effect of task demands by
      subtracting the ERP in the reading condition from the ERP in the counting
      condition. The difference ERP consisted of a negative deflection at 182 ms, and a
      positive deflection at 276 ms, which were both reduced in schizophrenic subjects.
      N2 and P3 amplitude to target stimuli were reduced in patients as well, but these
      abnormalities were uncorrelated with N1 and P2 abnormalities to non-target
      stimuli. Despite automatic registration of stimulus mismatch, and normal
      processing speed, patients showed deficient task-related modulation of processing
      to both non-target and target stimuli. Reduction of N1 amplitude in schizophrenia
      occurs regardless of task demands, and may reflect a chronic, early-stage
      disturbance in information processing.

PMID- 7806468
TI  - Stability of cardiovascular responses across subjects and situations: a
      systematic approach.
AB  - This study describes the reproducibility of behaviorally elicited cardiovascular
      response patterns, 111 subjects were studied over a 1-year interval.
      Physiological variables recorded were heart rate, systolic and diastolic blood
      pressure, and respiratory rate. Test-retest stability coefficients were
      calculated and compared with the results of a study with a 3-day interval between
      test sessions. The physiological data are depicted in a four-dimensional data box
      (subjects, situations, replications, variables), and the variance components of
      the factors and their interactions are estimated. Some of the interaction
      components are associated with specificity principles and with temporal
      stability. To comprehensively describe special aspects of stability, measures for
      stability were generated (concerning subjects, situations, or both), adopting
      basic ideas from the covariance partitioning approach. The stability measures
      were compared with simple test-retest reliability coefficients and with
      generalizability coefficients, and systematic relationships between the stability
      measures are discussed.

PMID- 7806469
TI  - Quantitative EEG modifications during the Cold Water Pressor Test: hemispheric
      and hand differences.
AB  - In a study designed to investigate the neurophysiological correlates of the Cold
      Water Pressor Test, a standardized experimental model of tonic pain, spectral
      EEGs were examined during the test in 15 young right-handed adults. Each subject
      performed a "cold water" and a "warm water" session. The subject immersed in cold
      water (0 degree C) either the right or the left hand alone, in a randomized way.
      EEG activity was recorded for an initial 3 min baseline and for the first and
      second minute epochs after immersion. A further EEG recording was obtained after
      a 30-min rest. Pain intensity was measured with a visual analogue scale. The EEG
      recordings showed several patterns of cortical activation during the test. Alpha
      2 desynchronization was more evident on the contralateral parietal electrodes of
      the stimulated hand and lasted longer over all the right hemisphere. Delta
      activity increased bilaterally, predominantly in the frontal leads. Stimulation
      of the left hand resulted in a higher delta increase during the second minute
      after immersion.

PMID- 7806470
TI  - Motor and non-motor components of the Contingent Negative Variation.
AB  - To study the contribution of the Stimulus-Preceding Negativity (SPN) to the late
      wave of the Contingent Negative Variation (CNV), negativity was recorded
      preceding an instruction stimulus (S1), an instruction stimulus to which a motor
      response was required (S2) and a stimulus that transmitted Knowledge of Results
      (KR). All recorded negativities showed a centro-parietal maximum. The pre
      instruction negativities tended to be larger over the left hemisphere, while a
      right hemisphere preponderance was found for the pre-KR negativity. Unlike the
      pre-S1 negativity, the pre-KR negativity may depend on affective-motivational
      processes. The pre-S1 negativity was small and influenced by factors other than
      the instruction at S1. It is concluded that the SPN contributes to the late CNV,
      but that this contribution was relatively small.

PMID- 7806471
TI  - Differential effects of visual attention on spontaneous and evoked otoacoustic
      emissions.
AB  - A visual task decreases evoked otoacoustic emissions (TEOAE) to an
      interindividually variable degree. The aim of these two studies was to assess
      whether the presence or absence of spontaneous otoacoustic emissions (SOAE) is
      involved in this variability. The first experiment investigated spontaneous
      otoacoustic emission (SOAE) frequency shifts during a visual attention task with
      a Fast Fourier Transform analysis, and found no attention effect on SOAEs. Using
      a larger subject pool, the second experiment concerned the attention effect on
      transiently evoked otoacoustic emissions and SOAE amplitude, using different
      measurement methods with the same visual task. The sample was composed of two
      groups of subjects: group A comprising subjects presenting SOAEs and group B
      subjects without SOAEs. A decrease in EOAE amplitude for group B during attention
      was observed and seems to confirm a possible influence of attention on the
      cochlea via the medial olivocochlear efferent system (MOES). The TEOAE amplitude
      of group A did not vary during attention, showing the peculiarity of this
      population of subjects and suggesting a different cochlear functioning.

PMID- 7806472
TI  - Return of auditory function following structural regeneration after acoustic
      trauma: behavioral measures from quail.
AB  - After measuring baseline behavioral audiograms, three of four behaviorally
      trained quail and fifteen untrained cohorts were exposed to a 1.5-kHz octave-band
      noise at 116-dB SPL for 4 h. The trained birds were tested daily following the
      exposure and showed a steady recovery of absolute sensitivity with a return to
      normal absolute thresholds by post-exposure days 8-10. Thirteen untrained cohorts
      were sacrificed after various survival times to evaluate the structural condition
      of the ear. The cohorts all showed regeneration of sensory cells similar to that
      seen in chicks. The effects of repeated acoustic trauma on recovery of
      sensitivity were evaluated by re-exposing the three trained birds and two
      untrained cohorts 106 days after the first exposure. One of the trained birds was
      exposed a third time, 113 days following the second exposure. The findings
      demonstrate that, following acoustic trauma, normal sensitivity returns prior to
      complete structural regeneration of the sensory epithelium and that repeated
      acoustic trauma may increase the time course of recovery of normal hearing
      sensitivity.

PMID- 7806473
TI  - Responses of inferior collicular neurons of the FM bat, Eptesicus fuscus, to
      pulse trains with varied pulse amplitudes.
AB  - Under free field stimulation conditions, we studied the responses of inferior
      collicular neurons of the FM bat, Eptesicus fuscus, to pulse trains with varied
      pulse amplitudes. Each pulse train consisted of 7 pulses of 4 ms delivered at 24
      ms interpulse-intervals (i.e. 42 pulses/s). For a control pulse train, all pulse
      amplitudes were equal to a neuron's best amplitude which, when delivered in
      single pulses, elicited maximal number of impulses from the neuron. The
      amplitudes of individual pulses of the remaining pulse trains were linearly
      increased or decreased at a slope of 0, 14, 28, 42, 56 and 69 dB/s. All 56
      inferior collicular neurons discharged to pulse trains were of two main types.
      Type I (N43, 77%) neurons discharged to each pulse within a train while type II
      (N11, 20%) neurons discharged to the first pulse of a train stimulus only.
      Discharge patterns of the remaining (N2, 3%) neurons changed between type I and
      type II when stimulated with different pulse trains. The number of impulses
      discharged by a neuron varied with different pulse trains. In addition, the
      number of impulses discharged to each pulse by type I neurons also varied among
      individual pulses within the train. Only 14 neurons (25%) discharged maximally to
      the control pulse train. Responses of the remaining neurons to other pulse trains
      were either 30%-120% larger than (N17, 30%) or within 30% (N25, 45%) of the
      control pulse train response. Furthermore, half of 56 neurons selectively
      discharged to a most preferred pulse train with a response magnitude which was at
      least 50% larger than the response to the least preferred pulse train. Possible
      mechanisms underlying the different discharge patterns are discussed in terms of
      a neuron's recovery cycle, minimum threshold and inhibitory period relative to
      the temporal characteristics (pulse repetition rate and amplitude) of the pulse
      trains.

PMID- 7806474
TI  - Ongoing proliferation of melanocytes in the stria vascularis of adult guinea
      pigs.
AB  - The intermediate cells of the stria vascularis are melanocytes derived from the
      neural crest. These internalized pigment cells have been thought to be a static
      population, distinct from those found in the skin. However, this investigation
      demonstrates that the melanocytes of the adult stria vascularis undergo
      continuous replication. Cell proliferation was studied using [3H]-thymidine
      autoradiography and bromodeoxyuridine (BrdU) immunohistochemistry. Single or
      multiple injections of [3H]-thymidine within a six hour period labeled a mean of
      9 intermediate cells. In pigmented guinea pigs, single daily injections of [3H]
      thymidine for 2 or 4 days labeled a mean of 24 and 69 intermediate cells,
      respectively; Pigmented guinea pigs given BrdU once daily for 2 or 4 days labeled
      a mean of 38 and 75 intermediate cells. By contrast, albino littermates also
      given BrdU averaged only 23 and 42 labeled intermediate cells in the same 2 and 4
      day experiments. The mean number of proliferating cells/mm of stria per 24 h was
      1.54 in the pigmented animals and 0.88 in the albinos. Both the total number and
      density of labeled intermediate cells were significantly smaller in the albino
      than the pigmented guinea pigs. These results demonstrate that the melanocytes in
      the stria vascularis undergo continuous baseline mitosis, and at a rate
      comparable to the melanocytes of the skin. This surprising similarity promotes
      the speculation that the proliferative rate of the strial melanocytes may be
      influenced by some of the same factors known to affect replication and pigment
      production in the skin.

PMID- 7806475
TI  - Inner-ear abnormalities and their functional consequences in Belgian Waterslager
      canaries (Serinus canarius).
AB  - Recent reports of elevated auditory thresholds in canaries of the Belgian
      Waterslager strain have shown that this strain has an inherited auditory deficit
      in which absolute auditory thresholds at high frequencies (i.e. above 2.0 kHz)
      are as much as 40 dB less sensitive than the thresholds of mixed-breed canaries
      and those of other strains. The measurement of CAP audiograms showed that the
      hearing deficit is already present at the level of the auditory nerve (Gleich and
      Dooling, 1992). Here we show gross abnormalities in the anatomy of the basilar
      papilla of Belgian Waterslager canaries at the level of the hair cell. The extent
      of these abnormalities was correlated with the amount of hearing deficit as
      measured behaviorally.

PMID- 7806476
TI  - Effects of hypergravity on statocyst development in embryonic Aplysia
      californica.
AB  - Aplysia californica is a marine gastropod mollusc with bilaterally paired
      statocysts as gravity-receptor organs. Data from three experiments in which
      embryonic Aplysia californica were exposed to 2 x g are discussed. The
      experimental groups were exposed to excess gravity until hatching (9-12 day),
      whereas control groups were maintained at normal gravity. Body diameter was
      measured before exposure to 2 x g. Statocyst, statolith and body diameter were
      each determined for samples of 20 embryos from each group on successive days.
      Exposure to excess gravity led to an increase in body size. Statocyst size was
      not affected by exposure to 2 x g. Statolith size decreased with treatment as
      indicated by smaller statolith-to-body ratios observed in the 2 x g group in all
      three experiments. Mean statolith diameter was significantly smaller for the 2 x
      g group in Experiment 1 but not in Experiments 2 and 3. Defective statocysts,
      characterized by very small or no statoliths, were found in the 2 x g group in
      Experiments 1 and 2.

PMID- 7806477
TI  - Early hair-cell degeneration in the extreme apex of the guinea pig cochlea.
AB  - Guinea pigs, aged from 3 weeks before term to 31 weeks after birth, were prepared
      for scanning electron microscopy. Examination of the extreme apex of the cochlea
      showed apparently pathological hair cells, even 3 weeks before term. The
      pathologies included loss and fusion of stereocilia, and the formation of giant
      stereocilia. The pathologies were most prevalent on row 3 of outer hair cells,
      declining to outer hair cell rows 2 and 1, with the inner hair cells being least
      affected. The abnormalities increased with time, increasing rapidly over the
      first few weeks of life, and more slowly thereafter. It is suggested that early
      degeneration in the extreme cochlear apex forms a novel model for spontaneous
      hair cell degeneration, with applicability to other types of spontaneous hair
      cell degeneration.

PMID- 7806478
TI  - Differences along the place-frequency map in the structure of supporting cells in
      the gerbil cochlea.
AB  - The function of supporting cells was investigated by comparing their morphologic
      adaptations at six different places in the gerbil cochlea. The volume of Deiters
      cells and tectal (cover) cells increased whereas that of Boettcher and Claudius
      cells decreased from base to apex. Deiters cells in the basal region tuned
      between 40 and 20 kHz lacked the unique rosette complex seen in regions encoding
      frequencies at or below 10 kHz. Deiters cells in high frequency regions differed
      from those at lower frequency places in several other ways: they possessed more
      apical microtubules, a larger basal microtubule stalk, mitochondria in the basal
      compartment, apical mitochondria that were unassociated with plasmalemma and more
      symmetric, and a less elaborately folded apicomedial plasmalemma enveloping fewer
      nerves. The tectal cells covering the outer tunnel appeared unlike Hensen cells
      in location and structure and differed further in exhibiting more variability
      with position in the cochlea. These covering cells in regions encoding high
      frequencies (20 and 40 kHz) extended a thin process medially that formed the roof
      of the outer tunnel and connected with the phalanx of the third Deiters cell. The
      tectal cells exclusively in places at 10 kHz or below projected numerous fimbriae
      into the outer tunnel. Hensen cells lateral to the cover cells also differed with
      frequency in showing abundant apical microvilli and mitochondria and basal
      juxtaposition to Boettcher cells only in the 40 to 20 kHz region. The observed
      structural differences provide evidence for functional variability along the
      place-frequency map. They attest to greater ion resorption from the outer tunnel
      by Deiters and tectal cells in low to mid frequency regions, and for greater ion
      exchange between endolymph and perilymph by Hensen, Boettcher and outer sulcus
      cells in regions of the cochlea encoding high frequencies. Amplification of the
      Deiters cells' microtubule system in the base of the cochlea possibly imparts
      increased stiffness to these cells and enhances transmission of mechanical energy
      at high frequency.

PMID- 7806479
TI  - Chirp evoked otoacoustic emissions.
AB  - The principles of short frequency sweeps (chirps) and their application to evoke
      transiently evoked otoacoustic emissions (TEOAE) are developed in comparison to
      using standard click stimuli. In contrast to click stimuli, chirp signals have
      the advantage of stimulating a freely selectable frequency range. In addition,
      chirp signals contain more energy than a click stimulus with the same maximum
      amplitude. The effects of different stimuli on TEOAE were investigated in normal
      hearing and hearing-impaired subjects. Using wide-band chirp signals yields a
      better signal-to-noise ratio compared to click stimulation. In addition, the
      stimulation of selected regions of the basilar membrane with frequency-limited
      chirps evokes TEOAE with frequency components that lie within the stimulated
      frequency range. The characteristic fine structure of this spectrum was found to
      be independent of the stimulus applied. The utilization of chirp stimuli appears
      to be useful for evoking TEOAE in, e.g., clinical applications.

PMID- 7806480
TI  - Piribedil affects dopamine turnover in cochleas stimulated by white noise.
AB  - The presence of dopamine (DA) within the cochlea has been previously reported,
      indicating that its turnover increases under noise stimulation. In the present
      report, piribedil, a dopaminergic D2 agonist, was used in order to provide
      evidence of the activity of D2 receptors in the turnover of DA under noise
      stimulation. Long-Evans rats were intraperitoneally injected with distilled water
      or with a solution of piribedil one hour previously to either noise or silence
      exposure. Noise stimulation was performed in an anechoic chamber at 70, 90 or 110
      dB SPL for one hour. The animals were then sacrificed and the cochlear contents
      of DA and its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic
      acid (HVA) were quantified by HPLC with electrochemical detection. The
      administration of piribedil to animals kept in silence did not modify the
      cochlear DA, DOPAC and HVA content. Noise stimulation resulted in a decrease of
      the cochlear DA content and an increase of the cochlear DOPAC and HVA contents in
      vehicle treated animals. The administration of piribedil resulted in a blockade
      of this noise induced cochlear DA turnover. These results suggest that piribedil
      stimulates cochlear D2 receptors controlling the cochlear DA release. Piribedil
      action on D2 receptors could explain the improvement observed in some cochleo
      vestibular diseases signs after piribedil treatment.

PMID- 7806481
TI  - Dynamic changes in tuning in the gerbil cochlea.
AB  - Afferent axons of the gerbil cochlear nerve were studied with reverse correlation
      analyses carried out with movable time windows and with noise that was modulated
      with a 10-Hz trapezoidal envelope that switched the noise amplitude between two
      levels, 20 dB apart. At the time of switching, the attributes of the axonal
      tuning curves derived in this manner switched very rapidly (e.g., within 10 ms)
      from those characteristic of lower-level stimuli to those characteristic of
      higher-level stimuli and vice versa. As previous investigators have shown, the
      attributes of tuning curves at higher levels include broader bandwidth and an
      accentuated low-frequency hump. Characteristic frequencies (CFs) of gerbil axons
      used in this study ranged from approximately 500 Hz to approximately 5 kHz. Over
      this range, the low-frequency hump was most pronounced in our studies for units
      with higher CFs, each of which showed a sharp high-frequency peak and a
      distinctly separate, broad low-frequency hump (reminiscent of the tip and tail of
      a conventional frequency-threshold tuning curve). The amplitude of the peak
      relative to that of the hump, and the breadth of the peak, both changed rapidly
      and reversibly following sudden change of noise level. Observation of such rapid
      changes of tuning would be difficult to achieve with conventional frequency
      threshold tuning curves, derived from tonal stimuli.

PMID- 7806482
TI  - Amplitude enhancement is seen in the cochlear nerve but not at, or before, the
      afferent synapse.
AB  - The amplitude of the cochlear nerve compound action potential (CAP) produced by a
      moderate intensity tonal stimulus (S2) can be enhanced when S2 is preceded by a
      low intensity S1 of the same frequency. The presence of S1 had no observable
      influence on the threshold of the CAP to S2. Enhancement was not observed in the
      cochlear microphonics or summating potentials. Deactivation of the contralateral
      olivocochlear bundle did not influence enhancement. Tetrodotoxin (TTX) was
      applied to the round window to block cochlear nerve spike activity, resulting in
      a residual EPSP-like potential, as described in the guinea pig by Dolan et al.
      (1989). Kainic acid, in turn, eliminated this EPSP-like response. Even though
      some differences were found in the responses of the gerbil and their guinea pig
      preparation to TTX and kainic acid, enhancement was not observed in this residual
      potential. When enhancement was observed at the level of the CAP, it was observed
      at brainstem levels. It is suggested that enhancement originates within the
      cochlear nerve axons.

PMID- 7806483
TI  - The osmotic response of the isolated tectorial membrane of the chick to isosmotic
      solutions: effect of Na+, K+, and Ca2+ concentration.
AB  - Changes in the size, shape, and structure of the isolated tectorial membrane of
      the chick were measured in response to isosmotic changes in the ionic composition
      of the perfusion solution. Substitution of artificial perilymph (AP) for
      artificial endolymph (AE) caused a small (approximately 15%), slow (time
      constants tau approximately 12 min) shrinkage of the thickness of the tectorial
      membrane that was largely reversed on return to AE. Substitution of AP for AE
      alters not only the predominate cation (from K+ to Na+) but also the Ca2+
      concentration (from < 7 mumol/l to 2 mmol/l). Additional experiments were
      performed to separate effects of each of these changes. When a high-Na+, low-Ca2+
      solution was substituted for a high-K+, low-Ca2+ solution (AE), the tectorial
      membrane swelled significantly, often to more than twice its original thickness
      (the largest swelling was 337%), with a slow time course (tau approximately 23
      min). Addition of the Ca2+ to either high-K+ or high-Na+ solutions caused rapid
      shrinkage of the tectorial membrane (tau approximately 2-3 min). Addition of the
      Ca2+ chelator EGTA caused rapid swelling (tau approximately 4 min). Large osmotic
      responses were only partially reversible and caused long-lasting changes. For
      example, long-duration solution changes that produced large, rapid osmotic
      responses early in an experiment tended to produce smaller and slower responses
      later in the experiment. In contrast, the small osmotic responses to short
      duration solution changes were repeatable for tens of hours. Changes in ionic
      composition of the bath affected not only the thickness of the tectorial membrane
      but also its other dimensions. Responses were not generally isotropic; both the
      size and shape of the tectorial membrane generally changed. Consistent changes in
      microstructure accompanied the osmotic changes.

PMID- 7806484
TI  - Modulation detection interference: across-frequency processing and auditory
      grouping.
AB  - Modulation Detection Interference (MDI) is the loss of sensitivity in processing
      amplitude modulation of a probe tone when a masker is similarly modulated. MDI
      was measured in four experiments to investigate two past claims concerning MDI:
      1) That MDI represents across-spectral processing, and 2) that MDI is the
      consequence of the auditory system using common patterns of amplitude modulation
      to group spectral components into a single auditory source. Experiment I studied
      MDI when the envelope phase of the masker and probe modulators were different and
      was used to address the issue of the extent to which MDI is a consequence of
      spectral grouping based on common amplitude modulation. Measures of MDI for
      conditions in which the frequency separation between the probe and masker
      carriers was varied (Experiment II), estimates of modulation depth discrimination
      (Experiment III), and signal detection thresholds for brief sinusoidal signals
      masked by amplitude modulated tones (Experiment IV) were all used to address
      issues related to across-spectral processing of amplitude modulation. The
      conclusions of these studies is that MDI is largely an across-frequency
      phenomenon and that the role of auditory grouping based on a common pattern of
      modulation can not be ruled out as having a relationship to MDI.

PMID- 7806485
TI  - Expression and localization of COL2A1 mRNA and type II collagen in human fetal
      cochlea.
AB  - The expression and localization of COL2A1 mRNA and protein was examined in human
      fetal cochlea to study the role of this gene in hearing and to begin to
      understand the pathogenesis of mutations in COL2A1 in hearing disorders. Northern
      blot analysis revealed COL2A1 expression in fetal membranous cochlea to be
      markedly greater than that in fetal skin, kidney, cartilage, eye and brain. In
      situ hybridization revealed COL2A1 expression in marrow cells, osteoblasts,
      fibroblasts and some osteocytes, in addition to chondrocytes in otic capsule. In
      the membranous cochlea, connective tissue elements (spiral ligament, spiral
      limbus and modiolar connective tissue), neuronal cells, secretory cells (stria
      vascularis) and organ of Corti cells (sensory hair cells) were found to express
      COL2A1. Immunohistochemistry was performed to assess distribution of type II
      collagen and correlation with COL2A1 mRNA in these morphologically and
      functionally diverse cell populations. In otic capsule, only cartilage was found
      to stain positively, and in membranous cochlea, only connective tissue structures
      including spiral ligament, spiral limbus, tectorial and basilar membranes,
      modiolar and spiral lamina cartilage contained type II collagen. Nonconnective
      tissue cells, marrow cells and osteoblasts did not contain immunohistochemically
      identifiable protein. Absence of type II collagen in a subset of cochlear cells
      may reflect potentially either inability to detect low levels of protein in these
      cells or posttranscriptional regulation.

PMID- 7806486
TI  - Central trajectories of type II (thin) fibers of the auditory nerve in cats.
AB  - This paper describes the central projections of thin fibers of the auditory nerve
      in cats. Both thin (type II) and thick (type I) fibers are labeled by
      extracellular injections of horseradish peroxidase (HRP) into the auditory nerve.
      Type I and almost all type II fibers bifurcate upon reaching the auditory nerve
      root of the cochlear nucleus. For a given bundle of auditory nerve fibers labeled
      by a discrete injection of HRP, bifurcations of type II and type I fibers are
      restricted to a narrow region of the nerve root. After the bifurcation, the
      pathways of type II branches within the anteroventral cochlear nucleus (AVCN) and
      posteroventral cochlear nucleus (PVCN) are similar to those of type I branches.
      This similarity in bifurcation and course of type I and type II fibers was
      observed in the ventral as well as dorsal parts of the ventral cochlear nucleus.
      The complete axonal course of most type II fibers could not be reconstructed,
      however, due to fading of the reaction product. Type II fibers produce very few
      collaterals in the cochlear nucleus (CN), but possess many 'en passant' swellings
      along their main processes and collaterals. Compared with type II fibers
      previously studied in mice (Berglund and Brown, 1989; 1994; Brown and Ledwith,
      1990), cat type II fibers are similar in their general projections within the
      main body of the nucleus and in the frequency of 'en passant' swellings per
      length of fiber, but cat fibers have a higher percentage of 'complex' or
      pedunculated 'en passant' swellings.

PMID- 7806487
TI  - Phase weighting: a method to improve objective detection of steady-state evoked
      potentials.
AB  - Objective response detection statistics such as magnitude-squared coherence (MSC)
      reflect the degree to which subaverage phases are clustered or dispersed, but not
      their agreement with an expected, or target, phase. Using signal-plus-noise
      simulations and human 40-Hz auditory evoked potentials, we tested MSC performance
      with and without phase weighting, in which MSC values were multiplied by weights
      related to the phase error between measured phase and target phase. Phase
      weighting improved MSC performance for both simulated and 40-Hz auditory evoked
      potential data. However, the improvement was greater for the simulations,
      probably because target phase was precisely known.

PMID- 7806488
TI  - Localization of osteopontin in the otoconial organs of adult rats.
AB  - Although it is known that mammalian otoconia consist of calcium bicarbonate and
      organic materials, none of the protein components have been identified in mammals
      at the molecular level, and the mechanisms of morphogenesis and calcification of
      the otoconia is still unclear. In the present study, we demonstrated the presence
      of osteopontin (OPN) in rat otoconia by using immunohistochemistry, and detected
      OPN mRNA in the sensory hair cells by a non-radioisotopic in situ hybridization
      technique. These results indicate that OPN is one of the protein components in
      rat otoconia and suggest that sensory hair cells are involved in the production
      of otoconia.

PMID- 7806489
TI  - Unified catalytic mechanism for DNA glycosylases.

PMID- 7806490
TI  - Rabphilin-3A is associated with synaptic vesicles through a vesicle protein in a
      manner independent of Rab3A.
AB  - Rabphilin-3A is a putative target protein for Rab3A small GTP-binding protein,
      which is implicated in regulated secretion, particularly in neurotransmitter
      release. Rabphilin-3A is associated with synaptic vesicles, although it has no
      transmembrane segment. Here we have studied how rabphilin-3A is associated with
      synaptic vesicles. Treatment of the synaptic vesicles isolated from rat brain
      with 1 M NaCl completely solubilized rabphilin-3A from the vesicles. These
      vesicles deprived of rabphilin-3A still contained Rab3A and synaptophysin.
      Exogenous rabphilin-3A bound to the vesicles deprived of endogenous rabphilin-3A
      in dose-dependent and saturable manners. The concentration of exogenous rabphilin
      3A giving a half-maximal binding was about 50 nM and maximally 5 +/- 1 molecules
      of exogenous rabphilin-3A bound to one vesicle. Addition of exogenous Rab3A bound
      to one vesicle. Addition of exogenous Rab3A or removal of endogenous Rab3A by the
      action of Rab GDI did not affect the binding of exogenous rabphilin-3A to the
      vesicles. However, treatment of the vesicles with trypsin completely abolished
      the binding of exogenous rabphilin-3A. These results suggest that rabphilin-3A is
      associated with synaptic vesicles at least through a vesicle protein in a manner
      independent of Rab3A.

PMID- 7806491
TI  - APP717 missense mutation affects the ratio of amyloid beta protein species (A
      beta 1-42/43 and a beta 1-40) in familial Alzheimer's disease brain.
AB  - We have biochemically purified A beta from brains of two unrelated familial
      Alzheimer's disease (FAD) pedigrees with the APP717 mutation (Val-->Ile) and from
      two sporadic Alzheimer's disease (AD) brains and characterized them by means of
      mass spectrometry and enzyme-linked immunosorbent assay. We observed two types of
      amyloid beta protein (A beta), the short-tail form (A beta 1-40) and the long
      tail form (A beta 1-42/43), in sporadic AD and FAD brains, and found that the
      ratio of the long-tail form of A beta (A beta 1-42/43) to total A beta was
      increased in FAD brains. These in vivo results were confirmed in vitro using
      cultured cells transfected with three kinds of APP cDNAs bearing the APP717
      mutations (Val-->Ile, Gly, or Phe). Taken together with the hypothesis that A
      beta 1-42/43 functions as a "seed" that increases the kinetics of amyloid fibril
      formation (Jarrett, J. T., and Lansbury, P. T., Jr. (1993) Cell 73, 1055-1058),
      we conclude that the APP717 missense mutation does not create new A beta species
      but promotes the increased accumulation of A beta 1-42/43 in the brain, which
      results in the enhancement of amyloid fibril formation from soluble A beta. These
      findings provide a causal relationship between this FAD genotype and the
      pathological phenotype of A beta deposition and senile plaque formation.

PMID- 7806492
TI  - Cucumisin, a serine protease from melon fruits, shares structural homology with
      subtilisin and is generated from a large precursor.
AB  - Cucumisin is a thermostable alkaline serine protease that is found in the juice
      of melon fruits (Cucumis melo L.). We have determined the complete nucleotide
      sequence of a cucumisin cDNA (2,552 nucleotides) and deduced the corresponding
      amino acid sequence. The open reading frame of the cDNA consists of 731 codons
      and encodes a large precursor (molecular weight, 78,815) relative to the observed
      size of mature native cucumisin (67 kDa). Sequence comparisons reveal that
      cucumisin has several features in common with the microbial proteases of the
      subtilisin family. The highly conserved sequences to the proximal regions of the
      catalytic triad amino acids Asp, His, and Ser, together with the substrate
      binding site in subtilisin, can be found within the deduced amino acid sequence
      of the protease domain of the cucumisin precursor. Cucumisin is the first known
      plant protease with such characteristics. Examination of the primary structure of
      cucumisin revealed that it is synthesized as a precursor, consisting of four
      functional domains: a possible signal peptide (22 amino acid residues), an NH2
      terminal pro-sequence (88 residues), a 54-kDa protease domain (505 residues),
      which is the active enzyme domain of the 67-kDa native cucumisin, and a 14-kDa
      COOH-terminal polypeptide (116 residues), which arises by limited autolysis of
      the 67-kDa native cucumisin. This structure of cucumisin suggests that it is
      probably synthesized as an inactive precursor.

PMID- 7806493
TI  - Regulation of interleukin (IL)-11 gene expression in IL-1 induced primate bone
      marrow stromal cells.
AB  - Interleukin (IL)-1 alpha treatment of a primate bone marrow stromal cell line, PU
      34, transiently increased the steady state level of IL-11 mRNA. Nuclear run-on
      experiments showed that the transcription rate of the IL-11 gene was not affected
      appreciably by IL-1 alpha induction, but changes in the half-life of the IL-11
      mRNA corresponded well with the changes in the steady state level of the IL-11
      mRNA during the induction. Although transient transfection of PU-34 cells with IL
      11 promoter constructs failed to respond to IL-1 alpha, a 10-base pair promoter
      region and JunD.AP-1 complex were found to be responsible for the basal level
      transcription of the IL-11 gene. The tyrosine kinase inhibitor genistein
      accelerated the degradation of the IL-11 mRNA without affecting the transcription
      rate of the IL-11 gene in IL-1 alpha stimulated cells. The insertion of DNA
      sequences corresponding to the 3'-untranslated region of the IL-11 gene into a
      rabbit beta-globin gene resulted in destabilization of the chimeric mRNA which
      failed to be induced by IL-1 alpha. Exogenous IL-11 expression generated from
      transient transfection with plasmid pCMV-IL-11, however, can be stabilized by IL
      1 alpha. In contrast to the hypothesis that AUUUA motifs in the 3'-untranslated
      region are sufficient to regulate cytokine mRNA stability, our results suggest
      that IL-1 alpha induced stabilization of the IL-11 mRNA requires participation of
      RNA sequences from different regions of the IL-11 message.

PMID- 7806494
TI  - Characterization, partial purification, and peptide sequencing of p130,the main
      phosphoprotein associated with v-Crk oncoprotein.
AB  - The transforming gene v-crk found in CT10 and ASV-1 avian sarcoma viruses induces
      marked phosphorylation of several proteins in cells expressing p47v-crk (v-Crk).
      In this work, the main tyrosine-phosphorylated proteins in ASV-1-infected chicken
      cells and v-crk-transfected rat cells were characterized biochemically. Both
      these proteins have a molecular mass of about 130 kDa and are tightly associated
      with v-Crk in vivo. Two-dimensional gel electrophoresis revealed that they are
      both essentially single proteins (p130) with modifications that result in a broad
      spot in an acidic region. The broad band of semi-purified p130 became sharp at an
      elevated position in the gel upon treatment with orthovanadate in vivo or with c
      Src kinase produced using a baculovirus vector in vitro, whereas it shifted at a
      lower position upon treatment with alkaline phosphatase in vitro. These results
      suggest multiple phosphorylation states of p130, which result in a broad band of
      p130. Two procedures of immunoaffinity purification were used to purify p130 from
      3Y1 cells transfected with v-crk. Approximately 30 pmol of purified p130 was
      obtained in an immobilized form on a filter starting from 3 x 10(10) cells.
      Peptide mapping of p130 digested in situ by peptidase revealed that the purity
      and quantity of the final material were enough for peptide sequencing. Several
      stretches of partial amino acid sequences were determined, and they indicated
      that p130 is a novel protein.

PMID- 7806495
TI  - Heparin cofactor II is regulated allosterically and not primarily by template
      effects. Studies with mutant thrombins and glycosaminoglycans.
AB  - Besides its critical role in hemostasis, the serine protease thrombin also
      participates in wound healing, inflammation, and atherosclerosis. Thrombin is
      inhibited by the serpins antithrombin and heparin cofactor II (HCiI) in reactions
      that are accelerated markedly by specific glycosaminoglycans. Following vascular
      injury, thrombin must be inhibited at both intravascular and extravascular sites
      that impose different constraints on the recognition of thrombin by these
      inhibitors. The present study examines the role of anion-binding exosite II of
      thrombin in the interaction with glycosaminoglycans and HCII. Acceleration of
      thrombin inhibition by serpins in the presence of glycosaminoglycans is proposed
      to occur by a template mechanism, in which inhibitor and protease bind
      simultaneously to the same glycosaminoglycan chain, facilitating their
      interaction. According to the template model, disruption of protease binding to
      glycosaminoglycan should significantly reduce acceleration of the inhibition.
      Specific mutations in exosite II (R89E, R245E, K248E, and K252E) disrupted
      thrombin binding to both dermatan sulfate and heparin, indicating that both
      glycosaminoglycans bind to a common site in exosite II. The same mutations
      markedly decreased the rate constant for thrombin inhibition by antithrombin
      heparin (up to 100-fold) but had little effect on the rate constant for thrombin
      inhibition by HCII-heparin (7-fold maximal reduction) and no effect on the rate
      constant for thrombin inhibition by HCII-dermatan sulfate. These results are
      incompatible with a template model for thrombin inhibition by HCII and dermatan
      sulfate. In the presence of glycosaminoglycan, HCII and antithrombin interact
      with opposing thrombin exosites and use distinct mechanisms of glycosaminoglycan
      catalysis. Antithrombin employs a template mechanism that requires heparin to
      interact with thrombin exosite II, whereas HCII employs an allosteric mechanism
      that requires thrombin exosite I but is largely independent of exosite II. These
      findings have potential implications for glycosaminoglycan therapy and for the
      respective physiologic roles of HCII and antithrombin.

PMID- 7806496
TI  - Post-transcriptional regulation of the cell surface expression of glycophorins A,
      B, and E.
AB  - GYPA, GYPB, and GYPE represent a small gene family localized on chromosome 4q28
      q31 that encodes the major red cell membrane glycophorins, GPA and GPB, and a new
      but as yet uncharacterized glycoprotein, GPE. There are 3-4 times more copies of
      GPA as compared with GPB on human erythrocytes (10(6) versus 2 x 10(5)
      copies/cell), whereas GPE is absent or poorly represented. Whether these
      quantitative differences reflect a transcriptional or post-transcriptional
      regulation was investigated. We found the functional activities of the
      glycophorin promoters to be similar, as shown by DNase I footprinting, gel
      retardation, methylation interference, and deletion analysis. Run-on analysis
      indicated that the transcription rate of each glycophorin gene in K562 cells was
      also very similar. However, large differences in mRNA decay were found in
      actinomycin-treated K562 cells. GPA transcripts were very stable (at least 24 h),
      whereas GPB transcripts were severely reduced after 17 h. The GPE transcripts
      were barely detectable and disappeared completely after 1 h. These results
      suggest that a difference in stability of the GPA, GPB, and GPE transcripts
      rather than a transcriptional regulation may predominantly account for the
      different levels of glycophorin expression on erythrocytes.

PMID- 7806497
TI  - The crystal structure of manganese peroxidase from Phanerochaete chrysosporium at
      2.06-A resolution.
AB  - The crystal structure of manganese peroxidase (MnP) from the lignin-degrading
      basidiomycetous fungus Phanerochaete chrysosporium has been solved using
      molecular replacement techniques and refined to R = 0.20 at 2.0 A. The overall
      structure is similar to that of two other fungal peroxidases, lignin peroxidase
      from P. chrysosporium and Arthromyces ramosus peroxidase. Like the other fungal
      peroxidases, MnP has two structural calcium ions. MnP also has two N
      acetylglucosamine residues N-linked to Asn131 that are readily visible in the
      electron density map. The active site, consisting of a proximal His ligand H
      bonded to an Asp residue and a distal side peroxide binding pocket consisting of
      a catalytic His and Arg, is the same as in the aforementioned fungal peroxidases
      as well as yeast cytochrome c peroxidase. MnP differs in having five rather than
      four disulfide bonds. The additional disulfide bond, Cys341-Cys348, is located
      near the C terminus of the polypeptide chain. Importantly, a new cation binding
      site, which we propose is the manganese-binding site of MnP, was located in the
      crystal structure. The ligands constituting the Mn(2+)-binding site include
      Asp179, Glu35, Glu39, a heme propionate, and two water molecules. Electron
      transfer from Mn2+ to the heme edge or iron center is envisioned to occur through
      a sigma-bonded pathway along a heme propionate.

PMID- 7806498
TI  - A single amino acid of the human gamma-aminobutyric acid type A receptor gamma 2
      subunit determines benzodiazepine efficacy.
AB  - Incorporation of the gamma 2 subunit into gamma-aminobutyric acid type A (GABAA)
      receptors is required for the expression of benzodiazepine pharmacology, but the
      regions of the subunit responsible for benzodiazepine actions have not been
      defined. Using mutagenesis, we identified a single amino acid of the gamma 2
      subunit of the human GABAA receptor that profoundly alters the nature of this
      pharmacology. When threonine 142 was mutated to serine, the benzodiazepine
      receptor antagonist, flumazenil, and the weak inverse agonist, Ro 15-4513, both
      acted as potent partial agonists. Further, potentiation of GABA responses by
      diazepam, alprazolam, clonazepam, or flunitrazepam doubled in receptors
      containing the Ser-142 gamma 2 subunit. In contrast, responses to the Type I
      benzodiazepine receptor selective ligands, zolpidem, alpidem, and CL218,872, were
      roughly halved. This change in pharmacology appears to occur at a stage following
      ligand binding, i.e. the mutation affects benzodiazepine efficacy. There was no
      effect on GABA affinity or efficacy or pentobarbital, Ro 5-4864, or alphaxalone
      modulation of GABA responses. These findings demonstrate that very minor changes
      in receptor structure can profoundly affect the efficacy of receptor ligands.
      Thus, agonism is determined not only by the structure of the drug, but also by
      the structure of the receptor, or protein complex, with which it interacts.

PMID- 7806499
TI  - A membrane-bound protein phosphatase type 2C from Paramecium tetraurelia.
      Purification, characterization, and cloning.
AB  - We isolated the first membrane-bound type 2C serine/threonine protein phosphatase
      from the ciliated protozoan Paramecium tetraurelia (PtPP2C). Three isozymes of
      33, 32, and 31 kDa with a specific activity of 1 mumol.min-1.mg1 were purified
      from the ciliary membrane. All enzymatic properties including (a) insensitivity
      toward inhibitors of other protein phosphatase families such as okadaic acid and
      microcystin, (b) absolute requirement for divalent cations, and (c) substrate
      specificity tested with synthetic phosphopeptides were identical to mammalian
      PP2C enzymes and identified the PtPP2C as a canonical PP2C in spite of it being
      about 25% smaller. The NH2-terminal was blocked. Microsequencing of six tryptic
      peptides established a relationship to other PP2C enzymes. The PtPP2C gene was
      obtained using degenerate oligonucleotide primers and the polymerase chain
      reaction. The gene coded for a 33-kDa protein with 300 amino acids and had an
      (A+T) content of 62%, typical for this protozoan. Nine of 15 Gln residues are
      encoded by TAA, a universal stop codon which codes for Gln in Paramecium. A large
      truncation at the COOH-terminal is responsible for the smaller size of the
      PtPP2C. Only a single transcript of 1 kilobase was detected with a Northern blot
      indicating that the 32- and 31-kDa proteins were proteolytic products of the 33
      kDa enzyme. Sequence comparisons with PP2C enzymes from rat, rabbit, yeast,
      Arabidopsis, and Leishmania defined a highly diverged enzyme family which shares
      three conserved domains, I, II, and III, accounting for about 25% of the primary
      structure. We demonstrated further that the distances between domains I/II and
      II/III are very similar in all PP2C enzymes (9-13 and 74-80 amino acids,
      respectively). However, the amino acid sequences of the spacer regions are
      unrelated. In addition, the COOH-terminal ends of 100-200 amino acids which
      comprise 30-50% of the enzyme, display no identity. A dendrogramm shows that
      PtPP2C surprisingly is most closely related to the mammalian PP2C, and enzymes
      from Leishmania, Arabidopsis, and yeast are more distant relatives.

PMID- 7806500
TI  - Four proline-rich sequences of the guanine-nucleotide exchange factor C3G bind
      with unique specificity to the first Src homology 3 domain of Crk.
AB  - The widely expressed cellular Crk protein has the domain structure SH2-SH3-SH3.
      We have previously demonstrated that the more N-terminal SH3 domain of Crk
      (CrkSH3(N)) specifically binds several cytoplasmic proteins. A cDNA encoding one
      of these proteins was isolated and found to have two different splice forms. The
      sequence is virtually identical to C3G, a guanine-nucleotide exchange factor. The
      center region of the 145-155-kDa protein contains four similar proline-rich
      sequences which are capable of binding individually to the SH3(N) domains of c
      Crk and v-Crk. Comparison of these sequences in C3G to proline-rich sequences in
      other Crk-binding proteins suggests that positively charged amino acids following
      the prolines play an important role in the binding to the CrkSH3(N) domain. The
      endogenous C3G could be coprecipitated with Crk from cell lysates of cells
      expressing high levels of c-Crk or v-Crk, suggesting high binding affinity and a
      possible interaction in vivo. Unlike many other SH3-binding proteins which
      interact with multiple SH3 domains, C3G from cell lysates binds preferentially to
      the CrkSH3(N) domain. This unique binding specificity supports the idea that C3G
      plays an important role in Crk signaling pathways.

PMID- 7806501
TI  - Building synthetic antibodies as adhesive ligands for integrins.
AB  - An antibody engineering strategy was employed to build high affinity ligands and
      antagonists of integrins alpha v beta 3 and alpha IIb beta 3. Previously, we
      inserted the integrin recognition motif, RGD, into the antigen binding site of a
      human antibody and selected the optimal flanking sequences from a phage-display
      library (Barbas, C. F., Languino, L. R., and Smith, J. W. (1993) Proc. Natl.
      Acad. Sci. U.S.A. 90, 10003-10007). The resulting antibody, Fab-9, blocked the
      function of integrin alpha v beta 3 but also bound to the ligand binding site of
      platelet integrin alpha IIb beta 3. In this report, the antibody engineering
      effort has been extended by 1) redesigning Fab-9 to achieve specificity for
      platelet integrin alpha IIb beta 3, 2) building non-RGD-containing antibodies
      that bind the ligand binding site of both beta 3-integrins, and 3) testing the
      hypothesis that peptides derived from complementarity determining regions (CDR)
      can be used to emulate the activity of the parent synthetic antibody. These goals
      were accomplished by subjecting the original antibody, Fab-9, to a "motif
      optimization" (MTF). A phage library was constructed in which the residues
      flanking the RGD motif in Fab-9 were maintained, but the RGDX sequence was
      randomized. This library was panned on purified alpha IIb beta 3 to identify high
      affinity binders. Four function-blocking antibodies lacking RGD, but with
      specificity for alpha IIb beta 3, were characterized. The antibody with the
      highest preference for alpha IIb beta 3, MTF-10, had an adhesion sequence of
      KGDN. This sequence is similar in primary structure to the active sequence within
      the disintegrin barbourin, which also antagonizes alpha IIb beta 3 (Scarborough,
      R. M., Rose, J. W., Hsu, M. A., Phillips, D. R., Fried, V. A., Campbell, A. M.,
      Nannizzi, L., and Charo, I. F. (1991) J. Biol. Chem. 266, 9359-9362). MTF-10 had
      a 70-fold higher affinity for alpha IIb beta 3 than alpha v beta 3. Through our
      selection strategy, we also identified several antibodies that lack RGD but still
      blocked ligand binding to both integrins with high affinity. Therefore, the RGD
      sequence is not necessary for a high affinity interaction with the ligand binding
      site of beta 3-integrins. Further investigation showed that the activity of
      inhibitory antibodies could be emulated by synthetic peptides derived from the
      protein sequences of the antibody's HCDR3. CDR-derived peptides blocked ligand
      binding to integrins and maintained essentially the same specificity as the
      parent antibody.

PMID- 7806502
TI  - Translocation of p72syk to the cytoskeleton in thrombin-stimulated platelets.
AB  - Thrombin stimulation induces a dramatic increase in the activity of p72syk in
      platelets. We have found that activated p72syk, which is phosphorylated on
      tyrosine residue(s), translocates from the Triton X-100-soluble fraction to the
      Triton X-100-insoluble, cytoskeleton-rich fraction after thrombin stimulation. In
      addition, the redistribution of p72syk from the 100,000 x g Triton X-soluble
      fraction and the membrane skeleton was found to correlate with an increased level
      of p72syk in the cytoskeleton. Furthermore, the early phase of p72syk
      translocation (within 60 s) was significantly inhibited with cytochalasin D,
      whereas the late phase of p72syk translocation (after 90 s) was completely
      inhibited with RGDS tetrapeptide treatment. These results suggest that
      translocation of the activated p72syk to the cytoskeleton correlates with
      different phases of the platelet activation process through actin polymerization
      and glycoprotein IIb/IIIa-fibrinogen-mediated aggregation of platelets and,
      hence, may have a regulatory role in tyrosine phosphorylation of platelets.

PMID- 7806503
TI  - Involvement of the COOH-terminal pro-sequence of Serratia marcescens serine
      protease in the folding of the mature enzyme.
AB  - The serine protease (SSP) from a Gram-negative organism, Serratia marcescens, is
      excreted even from Escherichia coli. The protease is synthesized as a 1045-amino
      acid precursor (preproSSP) composed of three functional portions, a typical NH2
      terminal signal peptide of 27 amino acids, the mature protease part of 618 amino
      acids, and a large COOH-terminal part of 400 amino acids. After the mature part
      (Ala28 to Asp645) has been liberated into the medium, most of the COOH-terminal
      part (Phe717 to Phe1045) remains stably in the outer membrane. When a mutated
      gene encoding the prepro-SSP with deletion of the junction region (Ser646 to
      Gly716) between the mature protease and the processed COOH-terminal protein was
      expressed in E. coli, the SSP protein was not detected in any fractions of the
      cells nor in the medium, whereas a processed COOH-terminal protein was found in
      the outer membrane. However, when the outer membrane fraction prepared from the
      transformant exhibiting the junction region (Ser646 to Gly716) probably on the
      cell surface was co-cultured with the transformant, SSP was found in the medium.
      Furthermore, a significant portion of the SSP protein denatured with guanidine
      hydrochloride was correctly refolded in vitro into the active protease, only in
      the presence of the outer membrane preparation from the transformant exhibiting
      the junction region. These results suggest that the junction region is exposed
      outside the cells, and it plays a role for guiding the folding of SSP in the
      correct conformation.

PMID- 7806504
TI  - Cation binding and conformational changes in VILIP and NCS-1, two neuron-specific
      calcium-binding proteins.
AB  - VILIP and NCS-1, neural-specific, 22-kDa Ca(2+)-binding proteins possessing four
      EF-hands, were expressed in Escherichia coli to study their divalent cation
      properties. Flow dialysis (Ca2+ binding) and equilibrium gel filtration (Mg2+
      binding) revealed that both recombinant proteins possess only two active metal
      binding sites, which can accommodate either Ca2+ or Mg2+. VILIP binds cations
      without cooperativity with intrinsic affinity constants K'Ca of 1.0 x 10(6) M-1
      and K'Mg of 4.8 x 10(3) M-1.Mg2+ antagonizes Ca2+ binding by shifting the
      isotherms to higher free Ca2+ concentrations without changing their shape. The
      competition equation yields a K'Mg, comp value of 180 M-1 for both sites. NCS-1
      binds two Mg2+ without cooperativity with K'Mg of 8.3 x 10(4) M-1 and two Ca2+
      with very strong positive cooperativity (nH = 1.96). In the absence of Mg2+ the
      K'Ca1 and K'Ca2 values are 8.9 x 10(4) and 1.4 x 10(8) M-1, respectively, which
      represent an allosteric increase of 1600-fold. Mg2+ shifts the Ca(2+)-binding
      isotherms to higher Ca2+ concentrations, yielding a K'Mg, comp value of 800 M-1
      for both sites. Thus VILIP and NCS-1 show three remarkable differences in the
      Ca2+/Mg2+ binding parameters: 1) VILIP binds Ca2+ with much lower affinity than
      NCS-1; 2) VILIP binds Ca2+ in a noncooperative way, whereas NCS-1 shows maximal
      positive cooperativity; 3) in VILIP the Mg2+/Ca2+ antagonism is much weaker than
      in NCS-1. Conformational changes monitored by Trp fluorescence indicate that the
      metal-free forms already are highly structured. Ca2+ binding promotes a 20-30%
      increase of fluorescence in both proteins, but whereas the Mg2+ form of VILIP has
      the same fluorescence properties as the metal-free form, Mg(2+)-saturated NCS-1
      has those of the Ca2+ form. Near UV difference spectra confirmed that in VILIP
      the Mg2+ form is very similar to the metal-free form; in NCS-1 it is different,
      especially in the Tyr region. NCS-1 possesses one unique Cys-38 in EF-hand site
      I. Its reactivity (kSH) toward 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB) is the
      same for the Ca(2+)- and Mg(2+)-loaded protein, but kSH is 4-fold higher in metal
      free NCS-1. VILIP possesses two additional thiols, one of which is inaccessible
      to DTNB in the native protein. The reactivity of the two accessible thiols is
      identical in the metal-free and Mg2+ forms and 5-fold higher than in the Ca2+
      form.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7806505
TI  - Characterization of the peptide substrate specificities of interstitial
      collagenase and 92-kDa gelatinase. Implications for substrate optimization.
AB  - The peptide substrate specificities of two matrix metalloproteinases (MMPs),
      interstitial collagenase (MMP-1), and 92-kDa gelatinase (MMP-9), have been
      examined. Starting with the parent substrate, Dnp-Pro-Leu-Gly approximately Leu
      Trp-Ala-D-Arg-NH2, four separate substrate mixtures were synthesized at subsites
      P2(Leu) through P2'(Trp). These mixtures contained either naturally occurring L
      amino acids, D-amino acids, or either of two distinct sets of miscellaneous amino
      acids. Combined, these mixtures gave 88 unique substitutions at each position
      and, over the four subsites, represented 352 potential substrates. Optimal
      substrates were identified using a combined high performance liquid
      chromatography/mass spectrometry analysis as previously reported. The results
      gave an extended profile of the substrate specificities for both MMP-1 and MMP-9
      at subsites P2(Leu) through P2'(Trp). Using the data obtained from the mapping, a
      new peptide substrate, Dnp-Pro-Cha-Abu approximately Smc-His-Ala-D-Arg-NH2 (where
      Dnp is 2,4-dinitrophenyl, Cha is cyclohexylalanine, Abu is alpha-aminobutyric
      acid, and Smc is S-methylcysteine) was designed and characterized. This peptide
      showed a 36-fold improvement in turnover (kcat/Km) versus the parent substrate by
      interstitial collagenase. In addition, some collagenase subsite specificities
      described here were found to be different from those previously reported.
      Experimental data show that the observed selectivity is dependent on the original
      peptide template employed, which has broader implications for substrate
      specificity studies.

PMID- 7806506
TI  - Biological activity of all-trans retinol requires metabolic conversion to all
      trans retinoic acid and is mediated through activation of nuclear retinoid
      receptors in human keratinocytes.
AB  - The biological activity of all-trans retinol, in human keratinocytes, was
      investigated through metabolic and functional analyses that assessed the capacity
      for retinol uptake and metabolism and the mechanism of retinol-induced activation
      of gene transcription. Human keratinocytes converted all-trans retinol
      predominantly to retinyl esters, which accounted for 60 and 90% of cell
      associated radiolabel after a 90-min pulse and a 48-h chase, respectively. Human
      keratinocytes also metabolized all-trans retinol to low levels of all-trans
      retinoic acid (11.47-131.3 ng/mg of protein) in a dose-dependent manner, between
      0.3 and 10 microM added retinol. Small amounts of 13-cis retinoic acid (5.47-8.62
      ng/mg of protein) were detected, but 9-cis retinoic acid was detected only when
      keratinocytes were incubated with radiolabeled retinol. There was no accumulation
      of the oxidized catabolic metabolites 4-hydroxy- or 4-oxoretinoic acid; however,
      5,6-epoxy retinoic acid was detected at pharmacological levels (10 and 30 microM)
      of added retinol. Biological activity of retinol was assessed through analysis of
      two known retinoic acid-mediated responses: 1) reduction of type I epidermal
      transglutaminase and 2) activation of a retinoic acid receptor-dependent reporter
      gene, beta RARE3-tk-CAT. Both all-trans retinol and all-trans retinoic acid
      reduced type I epidermal transglutaminase in a dose-dependent manner; however,
      the ED50 for all-trans retinol (10 nM) was 10 times greater than for all-trans
      retinoic acid (1 nM). All-trans retinol also stimulated beta RARE3-tk-CAT
      reporter gene activity in a dose-dependent manner. Half-maximal induction was
      observed at 30 nM retinol, which was again 10-fold greater than observed with all
      trans retinoic acid. Cotransfection of human keratinocytes with expression
      vectors for dominant negative mutant retinoic acid and retinoid X receptors
      reduced retinol-induced beta RARE3-tk-CAT reporter gene activation by 80%.
      Inhibition of conversion of all-trans retinol or all-trans retinaldehyde to all
      trans retinoic acid by citral reduced beta RARE3-tk-CAT activity 98 and 86%,
      respectively. These data demonstrate that retinol-induced responses in human
      keratinocytes are mediated by its tightly regulated conversion to retinoic acid,
      which functions as a ligand to activate nuclear retinoic acid receptors.

PMID- 7806507
TI  - Reconstitution of CD3 zeta coupling to calcium mobilization via genetic
      complementation.
AB  - The integrity of the T cell receptor complex (CD3-TCR) transduction machinery is
      central to T cell development and to T cell effector function. Molecular
      dissection of the multimeric CD3-TCR complex revealed that at least two
      associated polypeptides, CD3 zeta and CD3 epsilon, autonomously couple antigenic
      recognition event to early and late events of the intracytoplasmic activation
      cascade. A 18-amino acid motif based on a tandem YXXL stretch, the activation
      receptor homology sequence 1 (ARH-1) motif, is necessary and sufficient to the
      transducing properties of both CD3 zeta and CD3 epsilon. Stimulation of chimeric
      molecules made of ecto- and transmembrane domains of various cell surface
      proteins and intracytoplasmic domains of CD3 epsilon or CD3 zeta leads to an
      increase in the intracellular Ca2+ concentration ([Ca2+]i) in Jurkat cells. We
      describe here that a similar CD25/zeta chimeric molecule was unable to induce a
      detectable [Ca2+]i rise upon CD25 cross-linking once expressed in the murine
      thymoma BW-. A Ca2+ influx could, however, be triggered in BW- cells by
      thapsigargin, i.e. following depletion of Ca2+ stores. Somatic cell hybrids made
      from BW- and either thymocytes or mature lymph node T cells reconstituted the
      coupling of CD3 zeta to the Ca2+ signal via an ARH-1 motif-dependent pathway.
      However, pervanadate-induced Ca2+ mobilization, a phenomenon attributed to
      tyrosine phosphorylation, was impaired in BW-cells and reconstituted in
      hybridomas. In contrast to the Ca2+ response, IL-2 production was induced in both
      BW- and hybrids cells, which questions the functional relevance of [Ca2+]i
      augmentation in T cell activation. In conclusion, the properties of the BW-
      thymoma, which define a novel group of CD3 zeta transduction cell mutants, as
      well as its complementation by somatic cell fusion demonstrate that this cell
      line represents a useful model to dissect the signaling pathway that couples CD3
      zeta to Ca2+ mobilization by genetic reconstitution.

PMID- 7806508
TI  - The kaliotoxin family enlarged. Purification, characterization, and precursor
      nucleotide sequence of KTX2 from Androctonus australis venom.
AB  - Kaliotoxin (KTX) has been originally described as an inhibitor of the
      intermediate conductance Ca(2+)-activated K+ channel (Crest, M., Jacquet, G.,
      Gola, M., Zerrouk, H., Benslimane, A., Rochat, H., Mansuelle, P., and Martin
      Eauclaire, M.-F. (1992) J. Biol. Chem. 267, 1640-1647). However, the
      radioiodinated 125I-KTX-(1-37) was also able to bind to the dendrotoxin sensitive
      voltage-dependent K+ channel (Romi, R., Crest, M., Gola, M., Sampieri, F.,
      Jacquet, G., Zerrouk, H., Mansuelle, P., Sorokine, O., Van Dorsselaer, A.,
      Rochat, H., Martin-Eauclaire, M.-F., and Van Rietschoten, J. (1993) J. Biol.
      Chem. 268, 26302-26309). By following the ability to compete with 125I-KTX-(1-37)
      for binding to its receptor on rat brain synaptosomes, a new kaliotoxin-like
      peptide, KTX2, was isolated from Androctonus australis scorpion venom. It is a 37
      amino acid residue peptide, and its sequence shares 76% identity with KTX. The
      differences between the two peptides concern the NH2-terminal region and the
      residues 31 and 34 located in the region involved in the channel recognition.
      These differences may explain the 5-fold decrease of the molluscan Ca(2+)
      activated K+ channel blockage by KTX2 (kd = 135 nM) as well as of its binding
      affinity to rat brain synaptosomes (IC50 = 50 pM), compared with KTX. Specific
      antibodies raised against KTX-(1-37) were not able to recognize KTX2. Using
      degenerate primers, a 370-base pair cDNA encoding the KTX2 precursor was
      amplified by polymerase chain reaction from a cDNA library of A. australis venom
      glands. It encoded a presumed signal peptide of 22 residues followed by the
      sequence of the mature peptide.

PMID- 7806509
TI  - Chemical fatty acylation confers hemolytic and toxic activities to adenylate
      cyclase protoxin of Bordetella pertussis.
AB  - Adenylate cyclase toxin (ACT), a virulence factor of Bordetella pertussis,
      acquires hemolytic and toxic activities after post-translational modification of
      the cyaA gene product, CyaA. The exact nature of this modification is unknown,
      but homology to the related repeat toxin alpha-hemolysin of Escherichia coli
      suggests that fatty acylation of a lysine residue may be involved. In the present
      study, we used an in vitro chemical approach to acylate unmodified, inactive
      adenylate cyclase protoxin by using a new water-soluble compound,
      acylpyrophosphate. We show that undirected transfer of lauric, myristic, or
      palmitic acid chains to the CyaA protoxin is able to confer both hemolytic and
      toxic activities to ACT. The chemically modified protoxin shows a specific
      requirement for Ca2+ ions for toxic activity, as does the wild type toxin.
      However, the toxic and hemolytic activities of chemically modified ACT are low in
      comparison to ACT modified in vivo, suggesting that in vitro fatty acylation of
      the protoxin involves random modification of nucleophilic residues present in the
      toxin in contrast to the in vivo modification of specific sites.

PMID- 7806510
TI  - Differential activation of protein kinase C isoforms by endothelin-1 and
      phenylephrine and subsequent stimulation of p42 and p44 mitogen-activated protein
      kinases in ventricular myocytes cultured from neonatal rat hearts.
AB  - The translocation of protein kinase C (PKC) isoforms PKC-alpha, PKC-delta, PKC
      epsilon, and PKC-zeta from soluble to particulate fractions was studied in
      ventricular cardiomyocytes cultured from neonatal rats. Endothelin-1 (ET-1)
      caused a rapid ETA receptor-mediated translocation of PKC-delta and PKC-epsilon
      (complete in 0.5-1 min). By 3-5 min, both isoforms were returning to the soluble
      fraction, but a greater proportion of PKC-epsilon remained associated with the
      particulate fraction. The EC50 of translocation for PKC-delta was 11-15 nM ET-1
      whereas that for PKC-epsilon was 1.4-1.7 nM. Phenylephrine caused a rapid
      translocation of PKC-epsilon (EC50 = 0.9 microM) but the proportion lost from the
      soluble fraction was less than with ET-1. Translocation of PKC-delta was barely
      detectable with phenylephrine. Neither agonist caused any consistent
      translocation of PKC-alpha or PKC-zeta. Activation of p42 and p44 mitogen
      activated protein kinase (MAPK) by ET-1 or phenylephrine followed more slowly
      (complete in 3-5 min). Phosphorylation of p42-MAPK occurred simultaneously with
      its activation. The proportion of the total p42-MAPK pool phosphorylated in
      response to ET-1 (50%) was greater than with phenylephrine (20%). In addition to
      activation of MAPK, an unidentified p85 protein kinase was activated by ET-1 in
      the soluble fraction whereas an unidentified p58 protein kinase was activated in
      the particulate fraction.

PMID- 7806511
TI  - Histamine degradative uptake by cultured human pulmonary vascular endothelial
      cells utilizes an inflammatory cell diamine oxidase.
AB  - Neutrophil-endothelial interactions, altered clearance properties of the lung
      toward vasoactive mediators, and damaging effects of histamine that target the
      lung represent prominent elements of the inflammatory response at the systemic
      level. The pulmonary vasculature is unusual in that, unlike other tissues and
      vascular beds, it normally does not metabolize circulating histamine in vivo,
      although histamine-metabolizing enzyme activities have been detected in disrupted
      lung tissue. We have therefore explored the capability of human pulmonary artery
      endothelial cells in culture to express the receptor-mediated histamine
      degradative uptake system we previously defined in systemic endothelial cells
      (Haddock, R. C., Mack, P., Leal, S., and Baenziger, N. L. (1990) J. Biol. Chem.
      265, 14395-14401). Pulmonary endothelial cells display all components of this
      system: histamine methyltransferase generating the proximal cell-associated
      metabolite tele-methylhistamine and receptors binding diamine oxidase which
      generates the distal product methylimidazoleacetic acid that is accumulated by
      the cells. A diamine oxidase released from human neutrophil granules by
      activation with Ca2+ ionophore binds pulmonary and systemic endothelial cell and
      fibroblast diamine oxidase receptors and, thereby, participates in histamine
      degradative uptake. This enzyme utilizes cell-associated tele-methylhistamine as
      a substrate, preferentially generating methylimidazoleacetic acid in addition to
      reactive oxygen species. Thus the enzymatic and interactive cellular machinery
      for histamine clearance is inherently present as a functional unit in two major
      human pulmonary cell types. It interacts with products of inflammatory host
      defense cells, and pulmonary endothelial-neutrophil interactions via this pathway
      may influence the progression of inflammation.

PMID- 7806512
TI  - Flash-induced absorption spectroscopy studies of copper interaction with
      photosystem II in higher plants.
AB  - Measurements of flash-induced absorption changes at 325, 436, and 830 nm and of
      oxygen evolution were performed in order to analyze in detail the inhibition of
      photosystem II (PS II) by Cu(II) in PS II membrane fragments from spinach. (a)
      The kinetics of P680+ reduction become markedly slower in the presence of 100
      microM CuSO4. (b) The CuSO4-induced kinetics of P680+ reduction are dominated by
      a 140-160-microsecond decay. (c) The extent of these 140-160-microsecond
      kinetics, normalized to the overall decay, remains virtually unaffected by
      addition of the exogenous PS II donor, NH2OH. (d) In thoroughly dark-adapted
      samples the CuSO4-induced 140-160-microsecond kinetics are already observed after
      the first flash and remain unchanged by a train of excitation flashes. (e) The
      extent of P680+ and QA- formation under repetitive flash excitation is not
      diminished by addition of 100 microM CuSO4. (f) The induction of microsecond
      kinetics of P680+ reduction at the expense of ns kinetics and the inhibition of
      the saturation rate of oxygen evolution exhibit the same dependence on CuSO4
      concentration. (g) CuSO4 also transforms the 10-20-microsecond reduction of P680+
      by TyrZ in Tris-washed PS II membrane fragments into 140-160-microsecond kinetics
      without any effect on the extent of flash-induced P680+ formation. These results
      unambiguously show that Cu(II) does not affect the charge separation (P680+QA-),
      but instead specifically modifies TyrZ and/or its micro environment so that the
      electron transfer to P680+ becomes blocked.

PMID- 7806513
TI  - The thylakoid translocation of subunit 3 of photosystem I, the psaF gene product,
      depends on a bipartite transit peptide and proceeds along an azide-sensitive
      pathway.
AB  - Subunit 3 of photosystem I (PSI-3), the product of the nuclear psaF gene, is the
      docking protein for plastocyanin during photosynthetic electron transport in
      thylakoid membranes and is synthesized in the cytosol with a transit peptide that
      resembles structurally the bipartite targeting signals of hydrophilic, lumenal
      components such as plastocyanin. In organello import experiments performed with
      the authentic PSI-3 precursor and chimeric polypeptides consisting of residue
      correct fusions of transit peptides and mature proteins derived from different
      plastid proteins demonstrate that the PSI-3 transit peptide is indeed capable of
      translocating proteins into the thylakoid lumen and that, conversely, mature PSI
      3 depends on a bipartite transit peptide for its thylakoid transfer. Of the three
      recently described translocation/integration pathways for nucleus-encoded
      proteins carrying bipartite transit peptides that are distinct in their
      physiological requirements and strictly protein-specific, PSI-3, like
      plastocyanin and the 33-kDa protein of the oxygen-evolving complex, is
      translocated by a pathway that involves stromal factors but no proton gradient
      across the membrane. It is not affected by saturating amounts of the precursor
      for the 23-kDa protein of the oxygen-evolving complex that follows the latter
      route. Thylakoid translocation of PSI-3 is, however, impaired in the presence of
      sodium azide, which indicates that a homolog to the bacterial SecA protein might
      be involved in this process suggesting, thus, a prokaryote-like translocation
      pathway. The azide-sensitive factor appears to interact predominantly with the
      transit peptide of a precursor protein, since chimeras consisting of a
      presequence from an azide-resistant precursor and a mature part of an azide
      sensitive polypeptide are still translocated in the presence of the inhibitor.

PMID- 7806514
TI  - Covalent dimerization of vascular permeability factor/vascular endothelial growth
      factor is essential for its biological activity. Evidence from Cys to Ser
      mutations.
AB  - Vascular permeability factor, or vascular endothelial growth factor (VPF/VEGF) is
      an important factor in the regulation of vascular growth and vascular
      permeability. VPF is a secreted, dimeric protein and has 8 cysteine residues
      conserved with platelet-derived growth factor (PDGF). To study the role of some
      of these cysteine residues in maintaining the structure and function of VPF, we
      replaced the codons for the second, third, fourth, and fifth cysteine by serine
      codons, and expressed the mutant proteins in a mammalian expression system.
      Cysteine residues 2 and 4 in VPF were found to be directly involved in anti
      parallel interchain disulfide bonds, as in PDGF. VPF mutants lacking one of these
      cysteins were severely impaired in their S-linked dimerization, while upon
      coexpression of both mutants the ability to form dimers was restored. The VPF
      mutants lacking cysteine residue 2 or 4 also competed poorly for receptor binding
      of labeled VPF and had low biological activity, but these defects were also
      complemented by coexpressing the two mutants, indicating that for efficient
      receptor binding and activation VPF needs to be a covalent dimer, unlike PDGF-BB.
      Furthermore, cysteine residue 5 was found to be essential for VPF dimerization
      and activity, while the mutant lacking cysteine residue 3 was only mildly
      affected in its ability to dimerize and had partial biological activity.

PMID- 7806515
TI  - Expression of the neural axon adhesion molecule L1 in the developing and adult
      rat brain.
AB  - L1 is a developmentally regulated adhesion molecule that may play a role in some
      aspects of axonal guidance. With Northern blots we find peak expression of L1 RNA
      at postnatal day 1 (P1) in the developing rat brain. Western blots show a peak of
      protein on P15. The major form of L1 is 200 kDa, but lower molecular mass forms
      are found including 140 and 80 kDa, representing, respectively, the extracellular
      and intracellular regions of L1. All molecular mass forms of L1 change during
      development. Although expressed at lower levels than during development, L1 is
      found in all brain regions in the adult rat. Different regions of the brain show
      differential expression and regulation of L1 and its peptide fragments. For
      instance, the hypothalamus showed an enhanced L1-80/L1-200 ratio at P10 and P15
      relative to that expressed by cerebellum and hippocampus. Cerebellar granule
      cells in culture showed strong L1-200 and almost no L1-60, -80, or -140, in
      contrast to the intact cerebellum at the same age, which showed weaker L1-200 and
      strong L1-60, -80, and -140. Control experiments indicated that the L1
      proteolytic cleavage found in different developing brain regions occurred in vivo
      and was not a result of sample preparation. The amount of L1-200 in cultured
      granule cells was proportional to the measured length of the growing axon.
      Neuronal activity (increased with 25 mM K+, 100 microns N-methyl-D-aspartate, and
      100 microns 4-aminopyridine) enhanced L1 transcription and translation. Together,
      these data suggest differential regulation of L1 expression and proteolytic
      cleavage specific for developmental ages and brain regions.

PMID- 7806516
TI  - An Escherichia coli gene (FabZ) encoding (3R)-hydroxymyristoyl acyl carrier
      protein dehydrase. Relation to fabA and suppression of mutations in lipid A
      biosynthesis.
AB  - Escherichia coli strain SM101 harbors a temperature-sensitive allele (lpxA2) of
      the gene encoding UDP-Glc-NAc acyltransferase (the first enzyme of the lipid A
      pathway). SM101 is temperature-sensitive for lipid A biosynthesis and growth. To
      determine whether or not E. coli mutants lacking lipid A can be isolated, we
      examined temperature-resistant revertants of SM101. All regained the ability to
      synthesize lipid A. However, some were not true revertants but had acquired
      mutations in a neighboring gene (orf17), while retaining the original lpxA2
      lesion. Cell extracts of such revertants displayed 2-5 fold reductions in the
      specific activity of (3R)-hydroxymyristoyl-ACP dehydrase. Wild-type cells that
      overproduced the protein encoded by orf17 overproduced (3R)-hydroxymyristoyl-ACP
      dehydrase activity as much as 170-fold, suggesting that orf17 is the structural
      gene for the dehydrase. The proposed function of orf17 is further supported by
      its sequence similarity to fabA, the structural gene for (3R)-hydroxydecanoyl
      dehydrase of E. coli. We suggest that bypass of the lpxA2 phenotype by mutations
      in orf17 may be due to an increased (3R)-hydroxymyristoyl-ACP pool. The orf17
      gene (which we now designate fabZ) is not regulated by fadR. However, orf17 may
      be related to sefA, a suppressor of certain lesions in the cell division/lipid A
      biosynthesis gene, envA.

PMID- 7806518
TI  - Solution structure of GRO/melanoma growth stimulatory activity determined by 1H
      NMR spectroscopy.
AB  - The three-dimensional solution structure of the growth-related protein
      alpha/melanoma growth stimulatory activity (GRO/MGSA) has been solved by two
      dimensional 1H nuclear magnetic resonance spectroscopy. The GRO/MGSA monomer
      consists of an NH2-terminal loop, a three-stranded antiparallel beta-sheet, and a
      COOH-terminal alpha-helix. Dimerization, which is apparent under the experimental
      conditions used (2 mM, pH 5.10, 30 degrees C), results in a six-stranded
      antiparallel beta-sheet and a pair of helices with 2-fold symmetry. While the
      basic fold is similar to that seen for interleukin-8 (IL-8) (Clore, G. M.,
      Appella, E., Yamada, M., Matsushima, K., and Gronenborn, A. M. (1990)
      Biochemistry, 29, 1689-1696), there are differences in the ELR motif (residues 6
      8), the turn involving residues 31-36, which is linked to the NH2-terminal region
      through the 9-35 disulfide bond. The most significant differences are in the NH2
      terminal loop (residues 12-23). In IL-8, all the corresponding regions have been
      shown to be required for receptor binding (Clark-Lewis, I., Dewald, B.,
      Loetscher, M., Moser, B., and Baggiolini, M. (1994) J. Biol. Chem. 269, 16075
      16081). The structural differences thus have been identified between GRO/MGSA and
      IL-8 could contribute to their different receptor binding specificities.

PMID- 7806517
TI  - Expression of low molecular weight isoforms of microtubule-associated protein 2.
      Phosphorylation and induction of microtubule assembly in vitro.
AB  - In rat brain, the microtubule-associated protein 2 (MAP2) contains two low
      molecular weight isoforms, consisting of 467 and 498 amino acids and designated
      MAP2c and d, respectively. The present study describes the expression of these
      isoforms in Escherichia coli and their subsequent purification to homogeneity. On
      SDS-polyacrylamide gel electrophoresis, the recombinant proteins ran with
      apparent molecular masses of 69 and 74 kDa. A microtubule-assembling assay
      demonstrated that the recombinant protein was biologically active and that the
      tubulin polymerization rate for MAP2d was twice as fast as that for MAP2c. After
      dephosphorylation with alkaline phosphatase, preparations of low molecular weight
      MAP2 from fetal rat brain aligned with recombinant MAP2c. Moreover, recombinant
      MAP2c could be phosphorylated with a brain extract kinase activity, resulting in
      a reduced electrophoretic mobility similar to that observed in fetal MAP2.

PMID- 7806519
TI  - Gelsolin displaces phalloidin from actin filaments. A new fluorescence method
      shows that both Ca2+ and Mg2+ affect the rate at which gelsolin severs F-actin.
AB  - We describe an assay for measuring both the extent and kinetics of the severing
      of F-actin, based on the enhanced fluorescence emission of tetramethylrhodamine
      phalloidin bound to F-actin. The enhanced fluorescence is lost after exposure to
      active gelsolin by displacement of the phalloidin from actin during severing.
      This assay requires small amounts of actin and gelsolin, can be used to measure
      reaction times ranging from 1 to 10(3) s, and does not require covalent
      modification of either protein. The rate of fluorescence loss is linearly related
      to the concentrations of both actin and gelsolin. However, the apparent rate
      constant of the reaction is highly dependent on the divalent cation
      concentration, varying between 10(4) and 10(6) M-1 s-1 when the [Ca2+] varies
      between 20 and 200 microM. Addition of Mg2+ increases the apparent rate constant
      at equivalent Ca2+ concentration. These results suggest that in vitro the rate
      limiting step in the severing process is the activation of gelsolin by the
      binding of Ca2+ and Mg2+ to several low affinity (Kd approximately 100 microM)
      sites on gelsolin. While activation of gelsolin by Ca2+ is a slow process, the
      binding and severing of actin occurs at a rate approaching the diffusion limit.

PMID- 7806520
TI  - CGM2, a member of the carcinoembryonic antigen gene family is down-regulated in
      colorectal carcinomas.
AB  - We have determined the precise chromosomal location, the exon structure, and the
      expression pattern of CGM2, a member of the carcinoembryonic antigen (CEA) gene
      family. CGM2 cDNA was amplified by reverse transcription-polymerase chain
      reaction (RT/PCR) from the colon adenocarcinoma cell line, LS174T. A defective
      exon is missing from this cDNA clone, leading to a novel domain organization for
      the human CEA family with two immunoglobulin-like domains. The derived C-terminal
      domain predicts that the CGM2 protein is membrane-bound through a glycosyl
      phosphatidylinositol anchor. RT/PCR analyses identified CGM2 transcripts in
      mucinous ovarian and colonic adenocarcinomas as well as in adjacent colonic
      tissue, but not in other tumors including leukocytes from six chronic myeloid
      leukemia patients. Thus, unlike several other family members, CGM2 is not
      expressed in granulocytes but reveals a more CEA-like expression pattern.
      Northern blot analyses identified a 2.5-kilobase CGM2 mRNA that is strongly down
      regulated in colonic adenocarcinomas compared with adjacent colonic mucosa,
      suggesting a possible tumor suppressor function. In addition, a 3.2-kilobase
      transcript was observed in a number of colon tumors that is not detectable in
      normal colonic tissue. This mRNA species could represent a tumor-specific CGM2
      splice variant.

PMID- 7806521
TI  - Mechanisms of the transfer of aminoacyl-tRNA from aminoacyl-tRNA synthetase to
      the elongation factor 1 alpha.
AB  - Aspartylation of mammalian tRNAAsp by bacteria-expressed human aspartyl-tRNA
      synthetase (hDRS) was examined. The kinetics of the aspartylation of tRNA was
      consistent with the following reaction pathway, [formula: see text] where E,
      represents aspartyl-tRNA synthetase. A set of rate constants was obtained which
      fit single turnover time courses at varying concentrations of the enzyme, tRNA,
      and AMP using the SAAM program. The dissociation of Asp-tRNA (k3) was found to be
      rate limiting. The elongation factor 1 alpha (EF1 alpha) and GTP stimulated the
      hDRS aspartylation. The stimulation depended on the presence of both EF1 alpha
      and GTP. Kinetic analysis indicated that EF1 alpha formed a complex with the hDRS
      Asp-tRNA complex and stimulated the dissociation of Asp-tRNA. In the presence of
      0.5 M NH4Cl, which enhances the binding of Asp-tRNA by EF1 alpha, hDRS-bound Asp
      tRNA can be transferred directly to EF1 alpha. The implications of these results
      on the function of the multi-tRNA synthetase complex will be discussed.

PMID- 7806522
TI  - Characterization of a novel N-terminal peptide in human aspartyl-tRNA synthetase.
      Roles in the transfer of aminoacyl-tRNA from aminoacyl-tRNA synthetase to the
      elongation factor 1 alpha.
AB  - The kinetics of the N-terminal 32 residue-deleted human aspartyl-tRNA synthetase
      (hDRS delta 32) was analyzed. The kinetics of aspartyl-adenylate formation and
      Asp-tRNA synthesis by hDRS delta 32 were indistinguishable from those of hDRS.
      However, the dissociation of Asp-tRNA from hDRS delta 32 was much faster than
      that of hDRS. Unlike hDRS delta 32-catalyzed aspartylation of tRNA was not
      affected by the elongation factor 1 alpha. Two N-terminal peptides of hDRS,
      hDRS(T5-E26) and hDRS(D12-R27), were synthesized. Both peptides bind to tRNA
      Sepharose. Both peptides, hDRS(T5-E26) and hDRS(D12-R27), are monomeric and
      oligomerize at high peptide concentration or in 50% propylene glycol. The peptide
      hDRS(T5-E26) showed little alpha-helical content as analyzed by CD spectroscopy,
      while hDRS(D12-R27) showed appreciable alpha-helical contents in nonpolar
      solvents. These results suggest that the N terminus in hDRS may mediate the slow
      release of Asp-tRNA and facilitate the interaction of the hDRS.Asp-tRNA complex
      with the elongation factor 1 alpha. The demonstration of alpha-helix formation of
      the hDRS N-terminal peptide is consistent with the hypothetical amphiphilic helix
      of the N-terminal extension in hDRS. A model for the transfer of Asp-tRNA from
      hDRS to elongation factor 1 alpha is presented.

PMID- 7806523
TI  - Chimeric receptors indicate that phenylalanine 39 is a major contributor to
      insulin specificity of the insulin receptor.
AB  - The exact nature of how the insulin molecule interacts with the insulin receptor
      is obscure although chimeric receptors have shown that the ligand specificity of
      the insulin receptor and the IGF-I receptor (i.e. the sequences that discriminate
      between insulin and insulin-like growth factor I) reside in different regions of
      a common binding site and that the N-terminal 68 amino acids of the insulin
      receptor are involved in conferring specificity for insulin on this receptor
      (Kjeldsen, T., Andersen, A. S., Wiberg, F. C., Rasmussen, J. S., Schaffer, L.,
      Balschmidt, P., Moller, K. B., and Moller, N. P. H. (1991) Proc. Natl. Acad. Sci.
      U. S. A. 88, 4404-4408). Using chimeric insulin/IGF-I receptors to elucidate how
      the insulin receptor interacts with the insulin molecule we identified
      phenylalanine 39 of the insulin receptor as a major contributor in determining
      the receptor specificity for insulin, increasing insulin affinity 15-fold when
      replacing the corresponding amino acid in the insulin-like growth factor I
      receptor. Furthermore, replacement of the insulin receptor amino acid
      phenylalanine 39 with the corresponding IGF-I receptor amino acid, serine 35,
      decreased insulin affinity 8-fold.

PMID- 7806524
TI  - Complex organization of CTF/NF-I, C/EBP, and HNF3 binding sites within the
      promoter of the liver-specific vitellogenin gene.
AB  - Vitellogenin genes are expressed specifically in the liver of female oviparous
      vertebrates under the strict control of estrogen. To explain this tissue-specific
      expression, we performed a detailed analysis of the Xenopus laevis vitellogenin
      gene B1 promoter by DNase I footprinting and gel mobility-shift assays. We
      characterized five binding sites for the ubiquitous factor CTF/NF-I. Two of these
      sites are close to the TATA-box, whereas the others are located on both sides of
      the estrogen responsive unit formed by two imperfect estrogen response elements.
      Moreover two liver-enriched factors, C/EBP and HNF3, were found to interact with
      multiple closely spaced proximal promoter elements in the first 100 base pairs
      upstream of the TATA-box. To confirm the physiological significance of this in
      vitro analysis, in vivo DNase I footprinting experiments were carried out using
      the ligation-mediated polymerase chain reaction technique. The various cis
      elements characterized in vitro as binding sites for known transcription factors
      and more particularly for liver-enriched transcription factors are efficiently
      recognized in vivo as well, suggesting that they play an important role in the
      control of the liver-specific vitellogenin gene B1 expression.

PMID- 7806525
TI  - Characterization of four nucleic acid-binding single-chain Fv fragments by direct
      and competitive solid-phase radioimmunoassays.
AB  - The heavy- and light-chain variable region genes of four different nucleic acid
      binding antibodies (Jel 274 and Jel 72 (specific for duplex DNA), Jel 103
      (specific for poly(rI)), and Jel 318 (specific for DNA triplexes)) were cloned.
      Single-chain Fv fragments (scFv) in which the heavy and light chains were joined
      by a linker were constructed by polymerase chain reaction. The linker of 21 amino
      acids also served as a tag since it consisted of a repeating heptapeptide that
      was recognized by a specific antipeptide antibody. scFv were expressed in the
      cytoplasm of Escherichia coli as inclusion bodies. After purification and
      renaturation, a cross-linking assay was used to demonstrate that > 90% of scFv
      were in the form of monomers. The specificity of scFv was analyzed by both direct
      and competitive solid-phase radioimmunoassays. scFv.103 retained its specificity
      for poly(rI), whereas the other three scFv still bound the original antigen, but
      subtle changes in the overall specificity were noted. Thus, in some cases, the
      conformation of the binding site may be different in the context of an scFv
      compared with the original IgG.

PMID- 7806526
TI  - Purification and characterization of a multicomponent AP-1.junD complex from T
      cells. Dependence on a separate cellular factor for enhanced DNA binding
      activity.
AB  - TAP-1 (T-cell AP-1) is a previously identified DNA-binding activity that is
      rapidly induced in activated T cells in the absence of protein synthesis. This
      activity has been purified over 2,000-fold from the T-cell line MLA144. Purified
      TAP-1 is a multicomponent complex composed of 38-kDa and 43-kDa junD polypeptides
      in association with a separate factor(s), distinct from fos, that partly
      dissociate from the complex during affinity purification but is required for full
      TAP-1 DNA-binding activity. When reconstituted with TAP-1, this partly
      dissociated component strongly enhances the DNA-binding activity of the TAP-1
      complex. UV-cross-linking analysis identifies the dissociable component of the
      TAP-1 complex as a separate class of low molecular mass (23-29-kDa) DNA-binding
      polypeptide(s). 23-29-kDa polypeptides have been partially purified from nuclear
      extracts derived from MLA144 that enhance TAP-1 DNA-binding activity over 100
      fold and increase its contacts with flanking DNA sequence. These results define
      TAP-1 as a distinct AP-1.junD-containing complex in T cells whose DNA-binding
      activity is regulated by the interaction of distinct and separate cellular
      factor(s).

PMID- 7806527
TI  - Differential requirements for interleukin-2 distinguish the expression and
      activity of the cyclin-dependent kinases Cdk4 and Cdk2 in human T cells.
AB  - We examined the expression and activity of Cdk4 and Cdk2 in resting, competent,
      and proliferating normal human T cells. Expression of Cdk4 but not of Cdk2 was
      induced in competent T cells independent of an IL-2 signal. This up-regulation of
      Cdk4 mRNA and protein was resistant to the immunosuppressant drugs cyclosporin A
      (CsA) and FK506. A further increase in Cdk4 expression was seen upon stimulation
      of competent T cells by IL-2, as was de novo expression of Cdk2. Cyclin D2, a
      Cdk4 partner, showed similar patterns of regulation as Cdk4. The increases in
      Cdk4 and cyclin D2 expression seen in competent T cells were functionally
      significant since Cdk4 immunoprecipitates from these cells phosphorylated
      recombinant RB protein in vitro. Despite the lack of an increase in the
      expression of Cdk2, a small pool of pre-existing Cdk2 protein detected in resting
      T cells could be activated upon induction of competence. These data demonstrate
      that 1) the signals that lead to induction of competence in T cells stimulate an
      IL-2-independent and CsA-resistant phase of Cdk4 and cyclin D2 expression, Cdk4
      kinase activity, and Cdk2 kinase activity, and 2) IL-2 stimulates a second phase
      of Cdk4 and cyclin D2 expression and de novo expression of Cdk2 in these cells.
      The data show that the expression and activity of these major cell cycle
      regulatory proteins are controlled differentially by growth factors and indicate
      a role for Cdk4 and cyclin D2 in T-cell cycle entry and/or early G1 progression
      and for Cdk2 in later G1 progression and G1/S transition.

PMID- 7806528
TI  - Purification and characterization of a novel membrane-bound arginine-specific
      serine proteinase from porcine intestinal mucosa.
AB  - A novel membrane-bound serine proteinase has been purified from the microsomal
      membranes of porcine intestinal mucosa. It was solubilized from the microsomal
      membrane fraction with 1% sodium deoxycholate, then purified by a series of
      column chromatographic steps on DE52, butyl-Toyopearl, Bio-Gel P-150, Mono Q, and
      benzamidine-Sepharose in the presence of 0.02% Lubrol PX. Its molecular mass was
      estimated to be 50 kDa both by SDS-polyacrylamide gel electrophoresis under non
      reducing conditions and by gel filtration, and to be 32 kDa by SDS-polyacrylamide
      gel electrophoresis under reducing conditions, suggesting that the enzyme may
      exist as a homodimer in which two subunits are linked by disulfide bond(s). It
      had a pH optimum at around 9 and did not require Ca2+ for activity. It cleaved
      several peptide 4-methylcoumaryl-7-amide substrates almost exclusively after
      arginine residues, the best substrate among those tested being t-butyloxycarbonyl
      Gln-Ala-Arg-4-methylcoumaryl-7-amide. Various neuropeptides were also cleaved by
      this enzyme after arginine, mainly between paired basic amino acid residues, Arg
      Arg or Arg-Lys. Activity toward protein substrates was scarcely detected.
      Further, its partial amino acid sequences were highly homologous, but not
      identical, with those of trypsin-type serine proteinases. These results indicate
      that the present enzyme is a novel arginine-specific trypsin-like endopeptidase,
      possibly involved as a processing proteinase in the production of certain
      gastrointestinal neuropeptides or peptide hormones from their precursors, or
      their specific degradation.

PMID- 7806529
TI  - A novel glycosaminoglycan attachment domain identified in two alternative splice
      variants of human versican.
AB  - We have cloned an alternatively spliced glycosaminoglycan attachment domain (GAG
      alpha) of human versican from cDNA libraries derived from U251MG glioma cells.
      Inserted carboxyl-terminal of the hyaluronan-binding region, this domain adds
      another 987 amino acids to the original versican (V1) core protein giving rise to
      the large V0 isoform with 3396 amino acids and 17-23 putative glycosaminoglycan
      attachment sites. The GAG-alpha domain is encoded by exon 7 of the human versican
      gene (Naso et al., J. Biol. Chem., 32999-33008). Sequence comparisons revealed a
      slight similarity to the alternative splice domain of PG-M, further supporting
      the notion that PG-M is the chicken homologue of versican. On immunoblots of a
      proteoglycan preparation from U251MG culture medium, anti-GAG-alpha antibodies
      reacted exclusively with the larger of two versican core proteins recognized by
      antibodies against the original GAG-beta domain. Using reverse transcription
      polymerase chain reaction, we detected both the V0 and V1 isoforms in the
      cerebral cortex, aorta, intervertebral disc, liver, myometrium, and prostate,
      whereas keratinocytes exclusively expressed versican V1. In brain tissue, we
      identified a short versican variant (V2) including only the GAG-alpha domain. By
      expressing particular splice forms of versican, cells may control the hydration
      properties of their pericellular hyaluronan coat and thus could modulate
      interactions with the extracellular matrix or neighboring cells.

PMID- 7806530
TI  - Aggrecan synthesized by mature bovine chondrocytes suspended in alginate.
      Identification of two distinct metabolic matrix pools.
AB  - Proteoglycans synthesized by chondrocytes in alginate beads are found in two
      compartments: the cell-associated matrix and the further removed matrix
      (Hauselmann, H. J., Aydelotte M. B., Schumacher B. L., Kuettner K. E., Gitelis,
      S. H., and Thonar, E. J.-M. A. (1992) Matrix 12, 116-129). To study the
      metabolism of aggrecan in these two compartments, mature bovine articular
      chondrocytes in alginate beads were pulsed with [35S]sulfate for 30 min or 16 h
      on day 7 of culture and then chased in isotope-free medium for up to 21 days. At
      different times, the two matrix pools were separately isolated, and the 35S
      proteoglycans quantified, purified, and characterized. Radiolabeled aggrecan
      molecules exhibited a very long average half-life in the beads (t1/2 = 95 days).
      In contrast, small non-aggregating proteoglycans, which made up approximately 4%
      of the 35S-proteoglycans synthesized, were rapidly lost from the beads (t1/2 = <
      24 h). Approximately half the 35S-aggrecan subunits, representing mostly
      molecules which showed a delay in ability to form aggregates in the presence of
      exogenous hyaluronan and link protein, spent only a short time (t1/2 = 4 h) in
      the cell-associated matrix before moving into the further removed matrix. They
      exhibited a much longer average half-life in the beads than 35S-aggrecan
      molecules which became resident of the cell-associated matrix (t1/2 = > 95 days
      versus 15 days). Radiolabeled aggrecan subunits in the two matrix compartments
      had a similar average hydrodynamic size and polydispersity; importantly, the size
      of these molecules did not change during the chase period. Catabolism of 35S
      aggrecan in the cell-associated matrix was the only significant contributor to
      the appearance in the medium of partially degraded 35S-aggrecan which had lost
      the ability to bind to hyaluronan. These results strongly suggest aggrecan
      molecules which reside in the pericellular and territorial matrix compartments in
      close proximity to the chondrocytes have a much faster rate of turnover than
      their counterpart in the interterritorial areas further removed from the cells.

PMID- 7806531
TI  - Molecular interaction between ryanodine receptor and glycoprotein triadin
      involves redox cycling of functionally important hyperreactive sulfhydryls.
AB  - The fluorogenic maleimide 7-diethylamino-3-(4'-maleimidylphenyl)-4-methylcoumarin
      (CPM) has been shown to selectively form Michael adducts with hyperreactive
      sulfhydryls on the skeletal sarcoplasmic reticulum (SR) ryanodine receptor (RyR1)
      and triadin which are essential for normal Ca2+ channel function (Liu, G.,
      Abramson, J.J., Zable, A.C., and Pessah, I.N. (1994) Mol. Pharmacol. 45, 189
      200). The present report demonstrates a functionally important interaction
      between RyR1 and triadin which involves, in part, redox cycling of hyperreactive
      sulfhydryls in response to channel activation and inactivation. Nanomolar CPM is
      shown to selectively label RyR1 and triadin only in the presence of Ca2+ channel
      inhibitors (Mg2+, neomycin, ruthenium red, or anti-triadin antibody). Treatment
      of SR with channel activators (micromolar Ca2+, nanomolar ryanodine, or
      millimolar caffeine), 1) slows CPM labeling kinetics > 10-fold, 2) negates CPM
      labeling of channel-associated sulfhydryls, and 3) stabilizes a high molecular
      weight complex (HMWC) which appears on nonreducing SDS-polyacrylamide gel
      electrophoresis gels. The HMWC is positively identified as RyR1 and triadin by
      Western blot and immunoprecipitation analyses. High-affinity [3H]ryanodine
      binding sites are immunoprecipitated by either anti-RyR1 or anti-triadin antibody
      dose dependently. 1,4-Naphthoquinone (< or = 40 pmol/micrograms protein)
      selectively oxidizes hyperreactive sulfhydryls on RyR1 and triadin, induces Ca2+
      efflux from SR, and stabilizes the HMWC. The HMWC is reduced by beta
      mercaptoethanol or dithiothreitol into its component RyR1 and triadin promoters.
      The results provide direct evidence for the existence of a functionally important
      complex between RyR1 and triadin whose stability is determined by the redox state
      of hyperreactive sulfhydryl moieties which are allosterically regulated by
      physiological and pharmacological channel ligands. The present results suggest a
      possible molecular mechanism by which localized transient changes in the redox
      state within the RyR1-triadin complex can signal information across the SR
      membrane.

PMID- 7806532
TI  - Insect proteins homologous to mammalian high mobility group proteins I/Y (HMG
      I/Y). Characterization and binding to linear and four-way junction DNA.
AB  - A chromosomal high mobility group (HMG) protein from an epithelial cell line of
      Chironomus tentans (Diptera) was purified to homogeneity and chemically
      characterized. cDNA clones encoding this protein were isolated and sequenced. The
      deduced amino acid sequence revealed a high similarity to HMG protein I of
      mammalia. This insect protein has therefore been designated cHMGI. It has a
      deduced molecular mass of 10,371 kDa and appears to be a product of a single gene
      copy. Similarly to mammalian HMGI/Y proteins the insect cHMGI protein has three
      putative DNA-binding motifs with a sequence K/RXRGRP that are each encoded by one
      exon of the gene. Using synthetic peptides we have shown that the first and the
      second motif are necessary for high-affinity binding of the protein to DNA.
      Protein cHMGI binds preferentially to AT-rich DNA with a half-saturation value of
      1.1 nM. Both cHMGI and human HMGI proteins recognize specifically a four-way
      junction DNA. We have also purified a related protein with similar physico
      chemical properties from Drosophila melanogaster Kc cells. The identification and
      characterization of HMGI proteins in insects with polytene chromosomes and with
      the cytologic and genetic potential of Chironomus and Drosophila opens new
      possibilities for studying function(s) of this group of chromosomal proteins.

PMID- 7806533
TI  - Purification and characterization of bacteriophage T4 gene 59 protein. A DNA
      helicase assembly protein involved in DNA replication.
AB  - The T4 bacteriophage gene 59 protein is required for normal T4 DNA replication.
      We have purified this protein to homogeneity in two steps and show that it binds
      both to single-stranded DNA and to the T4 gene 32 protein, a DNA single strand
      binding protein. In in vitro assays, covering DNA with 32 protein makes this DNA
      inaccessible to the 41 protein, the highly processive DNA helicase, that
      associates with the T4 DNA primase (gene 61 protein) to form an active primosome.
      However, the 59 protein brings about the rapid assembly of 41 protein onto single
      stranded DNA, even if this DNA is covered with 32 protein. The 59 protein is
      therefore a DNA helicase assembly protein. The observed requirements for the 59
      protein in the vivo T4 DNA replication are explained by there being two
      alternative pathways for loading the 41 protein onto a replication fork at early
      times of T4 DNA synthesis, with only a 59 protein-mediated pathway remaining
      operative for the recombination-mediated replication that dominates later in
      infection (Barry, J., and Alberts, B. M. (1994) J. Biol. Chem. 269, 33063-33068).

PMID- 7806534
TI  - A role for two DNA helicases in the replication of T4 bacteriophage DNA.
AB  - The T4 bacteriophage gene 41 protein is the highly processive DNA helicase of the
      T4 primosome, a central part of the protein machinery that moves the T4 DNA
      replication fork. The T4 gene 59 protein accelerates the loading of 41 protein
      onto DNA covered with 32 protein (the T4 single strand binding protein), and it
      makes the 41 protein DNA helicase activity rapidly available to catalyze
      replication fork movement through a DNA double helix (Barry, J., and Alberts,
      B.M. (1994) J. Biol. Chem. 269, 33049-33062). With the aid of the 59 protein, we
      show that the T4 primosome (the T4 gene 41 and 61 proteins) can move rapidly
      through a promoter-bound RNA polymerase molecule that would otherwise stop
      replication fork movement. A second, very different DNA helicase, the T4 dda
      protein, provides an alternative pathway for replication past this DNA-bound RNA
      polymerase (Bedinger, P., Hochstrasser, M., Jongeneel, C. V., and Alberts, B.M.
      (1983) Cell 34, 115-123). Combined with other data, these in vitro experiments
      allow us to propose a model that explains why either the 59 protein or the dda
      protein, but not both, are required to begin efficient DNA replication inside the
      T4 bacteriophage-infected cell.

PMID- 7806535
TI  - The gene 59 protein of bacteriophage T4 modulates the intrinsic and single
      stranded DNA-stimulated ATPase activities of gene 41 protein, the T4 replicative
      DNA helicase.
AB  - The T4 gene 59 protein (gp59) serves as an accessory protein to the essential T4
      encoded DNA helicase, the gene 41 protein (gp41). gp59 stimulates gp41-dependent
      DNA synthesis reactions by promoting the assembly of gp41 onto single-stranded
      DNA (ssDNA), where the enzyme is activated to perform its DNA helicase functions.
      To better understand the mechanism of helicase-ssDNA assembly, we have studied
      the effects of gp59 on the intrinsic and ssDNA-stimulated ATPase activities of
      gp41. Our results indicate that gp59 exerts a direct effect upon the conformation
      and ATPase activity of gp41, by increasing the affinity of gp41 for ATP. In
      addition, we find that gp59 is nearly essential for promoting the assembly of
      gp41 onto ssDNA molecules that are covered with saturating amounts of the T4
      encoded helix-destabilizing protein, gene 32 protein (gp32). Results of protein
      affinity chromatography experiments suggest that gp59 contains distinct binding
      sites for gp41 and gp32 and may therefore act as a molecular adapter between the
      helicase and helix-destabilizing proteins. Together, the data indicate that
      specific gp59-gp41 and gp59-gp32 protein-protein interactions both play important
      roles in the assembly of the helicase onto single-stranded DNA.

PMID- 7806536
TI  - Escherichia coli DNA polymerase III holoenzyme footprints three helical turns of
      its primer.
AB  - Escherichia coli DNA polymerase III holoenzyme in the presence of ATP and E. coli
      single-stranded DNA-binding protein forms an initiation complex on a primed
      template capable of rapid and highly processive DNA replication. DNase I
      digestion of initiation complexes demonstrated that holoenzyme protected 27-30
      nucleotides of primer. Like the formation of initiation complexes, this
      protection required both ATP and E. coli single-stranded DNA-binding protein.
      Initiation complexes assembled with core DNA polymerase III (alpha, epsilon, and
      theta subunits), gamma-complex (gamma, delta, delta', chi, and omega) and the
      beta subunit produced a footprint identical to that formed with intact
      holoenzyme, indicating that initiation complexes formed with reconstituted enzyme
      and those formed with holoenzyme were equivalent. The presence of the tau subunit
      in reconstituted initiation complexes did not alter the DNase I footprint.
      Preinitiation complexes (gamma-complex plus beta subunit) assembled onto primer
      template in an ATP-dependent reaction protected a larger region of the primer
      than did holoenzyme. The addition of core DNA polymerase III to preintiation
      complexes restored the 30-nucleotide footprint observed with intact holoenzyme.
      These results suggest that holoenzyme subunits rearrange during initiation
      complex formation.

PMID- 7806537
TI  - Analysis of the Ras p21/mitogen-activated protein kinase signaling in vitro and
      in Xenopus oocytes.
AB  - Ras p21 in the GTP-bound form was shown to act as an upstream activator for
      mitogen-activated protein (MAP) kinase kinase (MAPKK) and MAP kinase, and Raf-1
      was reported to act as a MAPKK kinase. Further, physical association between Ras
      and Raf-1 was demonstrated. Here we have shown that incubation of Xenopus
      immature oocyte extracts with Ras enhances the ability of endogenous Raf-1 to
      activate MAPKK. Moreover, a dominant negative form of Raf-1 blocked the Ras
      induced activation of MAPKK and MAP kinase in the extracts, but not the cyclin A
      dependent activation of MAP kinase. When the extracts were depleted of 45-kDa
      MAPKK with polyclonal anti-MAPKK antibody, no activation of MAP kinase occurred
      even after incubation with Ras. These results suggest that Ras can activate the
      MAPKK kinase activity of Raf-1 in the extracts and that MAPKK is indispensable
      for the Ras-induced MAP kinase activation. It is well known that Ras can induce
      oocyte maturation when injected into immature Xenopus oocytes. Co-injection of
      Ras with an anti-MAPKK antibody that inhibits the MAPKK activity prevented the
      Ras-induced germinal vesicle breakdown, suggesting that MAPKK mediates, at least,
      one of cellular functions of Ras.

PMID- 7806538
TI  - Increased transcription and coordinate stabilization of mRNAs for secreted
      immunoglobulin alpha heavy chain and kappa light chain following stimulation of
      immunoglobulin A expressing B cells.
AB  - Immunoglobulin A (IgA) plays a key role in host protection at mucosal surfaces,
      yet little is known regarding the molecular mechanisms that govern the expression
      of this isotype. The studies herein investigated mechanisms that control IgA
      secretion in response to stimulation with interleukin-4 and interleukin-5,
      cytokines which are known to regulate IgA responses, and to bacterial
      lipopolysaccharide. Two mechanisms were shown to govern agonist induced IgA
      expression in a murine IgA expressing B cell line. In the initial period after
      stimulation, increased mRNA levels for the secreted form of alpha heavy chain
      (alpha s), and kappa light chain were paralleled by a transient increase in
      transcription rates of the corresponding genes. However, with prolonged agonist
      stimulation, gene transcription rates decreased to near control levels, and
      increased mRNA levels were associated with a coordinate increase in alpha s and
      kappa mRNA stability. In striking contrast, these agonists did not affect levels
      or stability of mRNA for the membrane form of alpha heavy chain (alpha m). Alpha
      s mRNAs contained multiple poly(A) addition sites located 13-32 nucleotides
      downstream of a single AAUAAA sequence. Nonetheless, the differential usage of
      these sites as a mechanism for controlling alpha s mRNA stability could be
      excluded, since the relative abundance of these different alpha s mRNAs did not
      differ significantly after agonist stimulation. These data, taken together,
      suggest that sequences within 107 nucleotides of the 3' end of alpha s mRNA,
      which are absent in alpha M mRNA, are required for the regulation of alpha s mRNA
      stability, possibly by acting as targets for regulated trans-acting cellular
      factors.

PMID- 7806539
TI  - Distinct negative regulatory mechanisms involved in the repression of human
      embryonic epsilon- and fetal G gamma-globin genes in transgenic mice.
AB  - A current model for human beta-globin gene switching proposes that the stage
      specific activation of embryonic and fetal globin genes requires the interaction
      of the beta-globin locus control region with proximal promoter elements.
      Subsequent repression in fetal and adult stages likely involves negative
      regulatory promoter elements and factors. To begin addressing these negative
      regulatory mechanisms, the regulation of human fetal G gamma-globin promoter
      fused to the SV40 T antigen gene was analyzed in transgenic mice. The results
      showed correct developmental expression in erythroid tissue, but lower levels of
      expression were also detected in non-erythroid tissue. Thus, the 5'-flanking G
      gamma-globin promoter sequence contains stage-specific erythroid elements but is
      lacking nonerythroid-specific negative elements. In contrast, the human embryonic
      epsilon-globin gene was only expressed in nonerythroid tissue of transgenic
      embryos, suggesting the presence of an erythroid-specific negative element(s).
      With the locus control region, complete repression of epsilon-globin RNA in fetal
      liver was observed in epsilon-globin genes without the previously characterized
      silencer, suggesting the presence of additional negative elements. Overall, this
      transgenic study suggests that distinct negative regulatory mechanisms function
      in the repression of embryonic and fetal globin genes.

PMID- 7806540
TI  - A mutant insulin receptor induces formation of a Shc-growth factor receptor bound
      protein 2 (Grb2) complex and p21ras-GTP without detectable interaction of insulin
      receptor substrate 1 (IRS1) with Grb2. Evidence for IRS1-independent p21ras-GTP
      formation.
AB  - The activation of p21ras by receptor tyrosine kinases involves the translocation
      of the growth factor receptor bound protein 2-mammalian son of sevenless protein
      (Grb2-SOS) complex to the plasma membrane where p21ras is localized. Insulin
      receptors induce p21ras-GTP formation by two possible mechanisms: tyrosine
      phosphorylation of insulin receptor substrate 1 (IRS1) and its subsequent
      association with Grb2, or Shc phosphorylation and its subsequent association with
      Grb2. We investigated the contribution of the major tyrosine autophosphorylation
      sites Tyr1158, Tyr1162, and Tyr1163 of the insulin receptor to IRS1.Grb2 and
      Shc.Grb2 association and the formation of p21ras-GTP. Chinese hamster ovary
      derived cell lines were used overexpressing mutant insulin receptors in which the
      major tyrosine autophosphorylation sites were stepwise replaced by
      phenylalanines. In cell lines expressing wild type or mutant Y1158F,Y1162,Y1163
      (FYY) receptors, insulin stimulated tyrosine phosphorylation of IRS1 and Shc and
      the formation of IRS1.Grb2 and Shc.Grb2 protein complexes, together with an
      increase in p21ras-GTP. Cell lines expressing mutant Y1158,Y1162F,Y1163F (YFF)
      receptors showed insulin-induced tyrosine phosphorylation of Shc, Shc.Grb2
      complex formation, and p21ras-GTP formation, whereas tyrosine phosphorylation of
      IRS1 was strongly decreased and formation of IRS1.Grb2 complexes was
      undetectable. The activity of FYY and YFF receptors to mediate p21ras-GTP
      formation correlated with their activity to induce Shc phosphorylation and
      Shc.Grb2 association. The mutant insulin receptors Y1158F,Y1162F,Y1163 and
      Y1158F,Y1162F,Y1163F were inactive in inducing any of these responses. We
      conclude that phosphorylation of Tyr1158 and Tyr1162 of the insulin receptor is
      linked to distinct post-receptor processes and that YFF receptors generate p21ras
      GTP via the Shc.Grb2 pathway rather than one involving IRS1.Grb2 interaction.

PMID- 7806541
TI  - Structure of a novel phosphocholine-containing glycoglycerolipid from Mycoplasma
      fermentans.
AB  - Mycoplasma fermentans is thought to be a pathogen of rheumatoid arthritis or
      cofactor of AIDS. A novel phosphocholine-containing glycoglycerophospholipid
      named GGPL-I was isolated from a M. fermentans-infected human helper T-cell
      culture. It was revealed that GGPL-I is a lipid component of the M. fermentans
      and a major immunological determinant. The GGPL-I was purified by DEAE-Sephadex
      column chromatography and repeated Iatrobeads column chromatography. The purified
      glycophospholipid was subjected to structural characterization by thin-layer
      chromatography, Fourier-transform infrared spectrometry, liquid secondary ion
      mass spectrometry, and nuclear magnetic resonance spectroscopy. Its structure was
      determined to be as follows: 6'-O-phosphocholine-alpha-glucopyranosyl-(1'-3)-1,2
      diacyl-sn-glycerol. This glycoglycerophospholipid is unique in containing
      phosphocholine, which is attached to C-6 of glucose. The stereospecific numbering
      (sn) of naturally occurring GGPL-I was determined through comparison with
      chemically synthesized compounds.

PMID- 7806542
TI  - A frameshift mutation in Exon V of the A alpha-chain gene leading to truncated A
      alpha-chains in the homozygous dysfibrinogen Milano III.
AB  - An inherited dysfunctional fibrinogen variant, denoted as fibrinogen Milano III,
      was found in a 13-year-old girl suffering from recurrent venous thrombosis.
      Plasma of the patient exhibited prolonged thrombin time and Reptilase time.
      Polymerization of fibrin monomers in the presence and absence of calcium ions was
      strongly impaired. SDS-polyacrylamide gel electrophoresis of reduced fibrinogen
      showed normal B beta- and gamma-chains, whereas no normal A alpha-chain was
      detected in the proposita. Immunoblot analysis with the monoclonal antibody Y18,
      detecting an epitope within the stretch of amino acids A alpha 1-51, revealed an
      A alpha-chain of about 50 kDa with an intact amino terminus. Immunoblotting with
      antibodies directed against serum albumin demonstrated the presence of albumin
      covalently linked to fibrinogen via a disulfide bridge. The structural defect of
      fibrinogen Milano III was determined by sequence analysis of a single-stranded
      fragment of genomic DNA amplified by polymerase chain reaction. An insertion of a
      thymine in the exon V of the A alpha-chain gene after the triplet ATT coding for
      IleA alpha 451 altered the reading frame and caused premature termination of the
      protein synthesis (Trp452(TGG)-Ser453(TCC)-Stop454(TGA)). In both parents, normal
      and mutant alleles were established, leading to duplication of the sequence
      pattern after the thymine insertion site, whereas the proposita is homozygous for
      the new mutation in the fibrinogen A alpha-chain gene.

PMID- 7806543
TI  - Thyroid hormone metabolism in a transthyretin-null mouse strain.
AB  - Transthyretin (TTR) is the principal carrier of thyroid hormones in rodent plasma
      and the major protein synthesized by the choroid plexus. Mice lacking TTR
      generated by targeted disruption (Episkopou, V., Maeda, S., Nishiguchi, S.,
      Shimada, K., Gaitanaris, G. A., Gottesman, M. E., and Robertson, E. J. (1993)
      Proc. Natl. Acad. Sci. U.S.A. 90, 2375-2379) had a 50% decrease in total
      thyroxine (T4) plasma levels but had normal free hormone levels as compared to
      wild-type mice. In the mutant serum there was increased T4 binding to thyroxine
      binding globulin. Thyroxine-binding globulin mRNA levels were the same in mutant
      and wild-type animals. Wild-type serum depleted of TTR also presented increased
      T4 binding to thyroxine-binding globulin, suggesting that TTR competes with
      thyroxine-binding globulin for T4 binding. Total and free triiodothyronine and
      thyrotoropin-stimulating hormone levels were not affected by the absence of TTR.
      Liver deiodinase-I activity, mRNA levels, and brain deiodinase-II activity were
      normal in the mutant mice, suggesting that the absence of TTR does not affect
      tissue thyroid hormone content. The low T4 levels found in the mutant mice sera
      cannot be accounted for by increased glucuronidation because the liver activity
      of UDP-glucuronosyltransferase was not affected in the TTR-deficient mice. We
      concluded that transthyretin-deficient mice are euthyroid in the absence of the
      major plasma T4 carrier. We ascribed this to the normal free hormone levels in
      the serum of the mutant mice. Our data, therefore, strongly supported the free
      hormone hypothesis for thyroxine uptake (Mendel, C. M. (1989) Endocr. Rev. 10,
      232-274).

PMID- 7806544
TI  - Identification of zinc ligands of the insulin-degrading enzyme.
AB  - The insulin degrading enzyme (IDE), a nonlysosomal enzyme involved in the
      metabolism of internalized insulin, is a member of a new family of
      metalloproteases which has an HXXEH active site motif. We have previously shown
      that both His108 and Glu111 within the HXCEH domain of human IDE are necessary
      for catalytic activity. Comparison to the prototypic zinc metalloprotease
      thermolysin, which contains an inversion of this motif, would predict that
      His112, as well as a downstream glutamate, serves as the second and third zinc
      ligands of IDE. To examine the role of His112, we mutated this residue to
      glutamine, leucine, or arginine. To identify a downstream zinc ligand, we
      substituted a glutamine for glutamate at either Glu182 or Glu189, both of which
      are conserved in human, rat, and Drosophila IDE. Vectors containing wild type or
      mutant IDE genes were transfected into COS cells, and the enzymes were analyzed
      for insulin degradation, insulin cross-linking, and zinc binding. Our results
      suggest that His108, His112, and Glu189 are the zinc ligands of human IDE, and
      Glu182 can influence zinc binding. In addition to a catalytic role, zinc binding
      to these residues appears to play a role in stabilizing the structure of the
      enzyme.

PMID- 7806545
TI  - Inhibition of tyrosine phosphorylation in the rat hepatic lectin 1 subunit of the
      rat asialoglycoprotein receptor prevents ATP-dependent receptor inactivation in
      permeabilized hepatocytes.
AB  - We previously reconstituted the ATP-dependent inactivation of asialoglycoprotein
      receptors (ASGPRs) in digitonin-permeabilized hepatocytes (Medh, J. D., and
      Weigel, P. H. (1991) J. Biol. Chem. 266, 8771-8778). Here we report that rat
      hepatic lectin 1 (RHL1) is the only ASGPR subunit that becomes radiolabeled when
      permeabilized washed hepatocytes are incubated at 4 degrees C in the presence of
      [gamma-32P]ATP; RHL2 and RHL3 are not radiolabeled. Phosphorylation of RHL1 was
      rapid (t1/2 appoximately 4 min) and complete within 30 min. Inclusion of 20 mM
      EDTA inhibited phosphorylation of RHL1 completely. Phosphoamino acid analysis
      identified Tyr(P) as the predominant (> 90%) radiolabeled phosphoamino acid.
      Addition of vanadate enhanced phosphorylation of Tyr in RHL1 4-fold.
      Phosphorylation of RHL1 occurred to the same extent in hepatocytes permeabilized
      with either 0.006% (w/v) or 0.055% digitonin and in the presence or the absence
      of ligand (50 micrograms/ml asialo-orosomucoid; ASOR) and/or 10 mM CaCl2.
      Sequential purification of active ASGPRs (using ASOR-Sepharose) and inactive
      ASGPRs from the ASOR-Sepharose flow-through (using anti-ASGPR antibody-Sepharose)
      demonstrated that radiolabeled RHL1 was present almost exclusively in active
      ASGPR oligomers. When permeabilized hepatocytes radiolabeled with [gamma-32P]ATP
      at 4 degrees C were warmed to 37 degrees C, a temperature at which ATP-dependent
      ASGPR inactivation occurs, RHL1 was dephosphorylated rapidly (t1/2 approximately
      4 min) and completely within approximately 30 min. Western blot analysis using a
      monoclonal anti-Tyr(P) antibody showed that the steady-state level of endogenous
      Tyr(P) in RHL1 doubled as a result of ATP treatment at 4 degrees C and then
      decreased to undetectable levels upon warming to 37 degrees C. The protein
      tyrosine kinase inhibitor tyrphostin 51 inhibited phosphorylation of RHL1 at 4
      degrees C and also prevented ATP-dependent ASGPR inactivation at 37 degrees C. We
      conclude that phosphorylation of Tyr in RHL1 of active ASGPRs is a prerequisite
      for ATP-dependent ASGPR inactivation.

PMID- 7806546
TI  - Insect immunity. Septic injury of Drosophila induces the synthesis of a potent
      antifungal peptide with sequence homology to plant antifungal peptides.
AB  - In response to a septic injury (pricking with a bacteria-soaked needle) larvae
      and adults of Drosophila produce considerable amounts of a 44-residue peptide
      containing 8 cysteines engaged in intramolecular disulfide bridges. The peptide
      is synthesized in the fat body, a functional homologue of the mammalian liver,
      and secreted into the blood of the insect. It exhibits potent antifungal activity
      but is inactive against bacteria. This novel inducible peptide, which we propose
      to name drosomycin, shows a significant homology with a family of 5-kDa cysteine
      rich plant antifungal peptides recently isolated from seeds of Brassicaceae. This
      finding underlines that plants and insects can rely on similar molecules in their
      innate host defense.

PMID- 7806547
TI  - Direct recognition of mRNA stop signals by Escherichia coli polypeptide chain
      release factor two.
AB  - The interaction between the translational stop signal and the polypeptide chain
      release factor protein (RF) within complexes of Escherichia coli ribosomes has
      been investigated by site-directed photochemical cross-linking experiments.
      Twelve mRNA analogues containing 4-thiouridine residues as part of stop signals
      were synthesized. Highly efficient cross-linking to RF-2 from 4-thiouridine (sU)
      residues of sUGAN-containing mRNAs was observed, and cross-linking from those of
      sUAAN was observed at a lower efficiency. This indicates that RF-2 is in close
      physical contact with the stop signal on the ribosome. The yield of the RF-2-mRNA
      cross-link depended on the identity of the fourth base for the sUGAN set of
      signals, suggesting that the fourth base of the stop signal affects the
      interaction between RF-2 and the stop codon. A region previously implicated as
      part of the decoding site of the small ribosomal subunit, 1385-1420 of the 16 S
      rRNA, was also cross-linked with these mRNAs. No new cross-links were obtained in
      the presence of the release factor. The data are consistent with models in which
      the RF has an anticodon-like domain that contacts the stop signal directly at or
      near the ribosomal site in which sense codons are decoded.

PMID- 7806548
TI  - Norepinephrine utilizes alpha 1- and beta-adrenoreceptors synergistically to
      maximally induce c-fos expression in brown adipocytes.
AB  - In order to examine how norepinephrine stimulates proliferation and
      differentiation in brown fat cells, we have investigated the ability of brown fat
      cells to respond to norepinephrine stimulation with an increase in the expression
      of the proto-oncogene c-fos. Stimulation of brown fat precursor cells (isolated
      from young mice and grown for 4 days in culture) with norepinephrine led to a
      marked but transient (maximal approximately 30 min) induction of c-fos
      expression. The magnitude of this induction was similar in pre- and postconfluent
      cells. The norepinephrine effect could be blocked by both alpha 1- and beta
      adrenergic antagonists. Forskolin had a small inductive ability, as had the
      selective alpha 1-agonist cirazoline, but with both together a high induction was
      obtained. The phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) could in
      itself induce c-fos expression, but pretreatment with TPA did not abolish the
      ability of norepinephrine to induce c-fos expression, indicating that TPA
      sensitive protein kinase C was not a primary mediator in this pathway. Also the
      Ca2+ ionophore A23187 had in itself an inductive ability, but A23187 in
      combination with forskolin led to a large increase in c-fos expression,
      indicating synergistic interaction between a cAMP pathway and a [Ca2+]i pathway.
      This interaction was not proximal, i.e. alpha 1 stimulation or increase in
      [Ca2+]i by A23187 did not augment forskolin-induced cAMP levels, and beta
      stimulation or forskolin did not affect [Ca2+]i levels; and it did not require
      protein synthesis. It was concluded that norepinephrine, in agreement with its
      fundamental role in the control of brown fat cell growth and development, was
      able to induce c-fos expression, that this induction was not exclusively linked
      to promotion of either proliferation or differentiation, and that the induction
      was mediated via a distal synergism between beta/cAMP and alpha 1/[Ca2+]i
      pathways, thus conferring to the alpha 1-adrenoreceptors on the cell a
      potentially significant role in the control of cell growth and development.

PMID- 7806549
TI  - 3-D attitude representation of human joints: a standardization proposal.
AB  - In view of the singularities, asymmetries and other adverse properties of
      existing, three-dimensional definitions for joint and segment angles, the present
      paper proposes a new convention for unambiguous and easily interpretable, 3-D
      joint angles, based on the concept of the attitude 'vector' as derived from
      Euler's theorem. The suggested standard can be easily explained to non
      mathematically trained clinicians, is readily implemented in software, and can be
      simply related to classical Cardanic/Eulerian angles. For 'planar' rotations
      about a coordinate system's axes, the proposed convention coincides with the
      Cardanic convention. The attitude vector dispenses with the 'gimbal-lock' and non
      orthogonality disadvantages of Cardanic/Eulerian conventions; therefore, its
      components have better metrical properties, and they are less sensitive to
      measurement errors and to coordinate system uncertainties than Cardanic/Eulerian
      angles. A sensitivity analysis and a physical interpretation of the proposed
      standard are given, and some experimental results that demonstrate its
      advantages.

PMID- 7806550
TI  - Instantaneous helical axis estimation from 3-D video data in neck kinematics for
      whiplash diagnostics.
AB  - To date, the diagnosis of whiplash injuries has been very difficult and largely
      based on subjective, clinical assessment. The work by Winters and Peles Multiple
      Muscle Systems--Biomechanics and Movement Organization. Springer, New York (1990)
      suggests that the use of finite helical axes (FHAs) in the neck may provide an
      objective assessment tool for neck mobility. Thus, the position of the FHA
      describing head-trunk motion may allow discrimination between normal and
      pathological cases such as decreased mobility in particular cervical joints. For
      noisy, unsmoothed data, the FHAs must be taken over rather large angular
      intervals if the FHAs are to be reconstructed with sufficient accuracy; in the
      Winters and Peles study, these intervals were approximately 10 degrees. in order
      to study the movements' microstructure, the present investigation uses
      instantaneous helical axes (IHAs) estimated from low-pass smoothed video data.
      Here, the small-step noise sensitivity of the FHA no longer applies, and proper
      low-pass filtering allows estimation of the IHA even for small rotation velocity
      omega of the moving neck. For marker clusters mounted on the head and trunk,
      technical system validation showed that the IHAs direction dispersions were on
      the order of one degree, while their position dispersions were on the order of 1
      mm, for low-pass cut-off frequencies of a few Hz (the dispersions were calculated
      from omega-weighted errors, in order to account for the adverse effects of
      vanishing omega). Various simple, planar models relating the instantaneous, 2-D
      centre of rotation with the geometry and kinematics of a multi-joint neck model
      are derived, in order to gauge the utility of the FHA and IHA approaches. Some
      preliminary results on asymptomatic and pathological subjects are provided, in
      terms of the 'ruled surface' formed by sampled IHAs and of their piercing points
      through the mid-sagittal plane during a prescribed flexion-extension movement of
      the neck.

PMID- 7806551
TI  - The effect of residual strain on the diastolic function of the left ventricle as
      predicted by a structural model.
AB  - The unloaded heart is not stress-free. It is subjected to residual stress and
      strain. Their extent and influence on the global performance of the left
      ventricle and on local phenomena in the ventricular wall are studied by model
      simulation. The analysis focuses on the equatorial region of the ventricle, with
      an approximate thick-walled cylindrical geometry. The in vivo myocardium is
      considered to be incompressible, consisting of fibers embedded in a fluid matrix,
      with transmurally varying anisotropic microstructure in accordance with
      morphological characteristics. The results show that residual strain is
      transmurally distributed with a pattern and magnitude which agree well with
      measurements. The calculated residual strains are within mean +/- one standard
      deviation of the measured ones. Their magnitude was found to increase with
      increasing opening angle and with increasing wall thickness. The residual strain
      was found to have several effects on ventricular function: At volumes higher than
      the reference one it gives rise to more uniform transmural distributions of
      stress and intramyocardial pressure; it causes about 50% increase in the
      ventricular compliance at high volumes and doubles the suction of atrial blood at
      low volumes, thus facilitating the diastolic filling. In addition, residual
      strains cause bias of in vivo measured strains from their true values. This may
      significantly affect physiological interpretation of measured ventricular
      deformations. In conclusion, the present structural analysis predicts that
      residual strain has favorable effect on left-ventricular diastolic performance,
      and gives rise to more uniform ventricular stress distribution.

PMID- 7806552
TI  - Translational and rotational joint power terms in a six degree-of-freedom model
      of the normal ankle complex.
AB  - We hypothesized that defining joint power (JP) merely on the basis of joint
      rotations ignores important translational power terms, and may not adequately
      represent the energy flow profile for a given muscle group. A novel six degree-of
      freedom (6 DOF) model of the ankle complex was implemented, accounting for
      previously ignored joint translations as well as traditional rotations. Foot and
      shank kinematic and kinetic data were collected over a stride cycle on five male
      and five female adults, walking five trials each at 0.69 statures s-1. During
      intra-subject analyses, ensemble averages were calculated (n = 5) for JP
      associated with each DOF, and for related velocity and force/moment data.
      Translational joint velocities typically peaked below 10% of the mean walking
      velocity. The largest peak in JP occurred for the rotational DOF associated with
      dorsi/plantar flexion (360 W). The next largest peak in JP was for the vertical
      translational DOF, and was nearly 10% of the predominant peak. Positive work
      during push-off was significantly less p < or = 0.05) for the 6 DOF model (27.9
      J) than for either 1 or 3 DOF rotational models (30.3 and 29.9 J, respectively).
      Negative work during early stance was significantly less for the 6 DOF model (
      10.3 J) than for either the 1 or 3 DOF models (-13.1 and -12.6 J, respectively).
      Inter-subject analyses (n = 50) were conducted for JP data only, with similar
      results. We conclude that translational JP terms are of practical importance in
      mechanical energy studies, and may be of particular concern when evaluating
      energy storing prostheses, when summing total power at several joints, and when
      studying pathologies that disturb joint geometry.

PMID- 7806553
TI  - A comparison of muscular mechanical energy expenditure and internal work in
      cycling.
AB  - The hypothesis that the sum of the absolute changes in mechanical energy
      (internal work) is correlated with the muscular mechanical energy expenditure
      (MMEE) was tested using two elliptical chainrings, one that reduced and one that
      increased the internal work (compared to circular). Upper and lower bounds were
      put on the extra MMEE (work done by net joint torques in excess of the external
      work) with respect to the effect of intercompensation between joint torques due
      to biarticular muscles. This was done by having two measures of MMEE, one that
      allowed no intercompensation and one that allowed complete intercompensation
      between joints spanned by biarticular muscles. Energy analysis showed no
      correlation between internal work and the two measures of MMEE. When compared to
      circular, the chainring that reduced internal work increased MMEE, and phases of
      increased crank velocity associated with the elliptical shape resulted in
      increased power absorbed by the upstroke leg as it was accelerated against
      gravity. The resulting negative work necessitated additional positive work. Thus,
      the hypothesis that the internal work is correlated with MMEE was found to be
      invalid, and the total mechanical work done cannot be estimated by summing the
      internal and external work. Changes in the dynamics of cycling caused by a non
      circular chainring may affect performance and must be considered during the non
      circular chainring design process.

PMID- 7806554
TI  - Stress relaxation behaviour of trabecular bone specimens.
AB  - The present study defines several conditions under which stress relaxation tests
      can be performed and investigates the viscoelastic behaviour of trabecular bone
      in compression through a series of stress relaxation tests at three strain levels
      and in three loading directions of each cubic specimen. A viscoelastic model is
      proposed to characterize the behaviour of trabecular bone and a spectrum of
      relaxation times is determined. Trabecular bone from the femoral head is non
      linearly viscoelastic and displays anisotropic behaviour, which cannot be more
      symmetric elastically than orthotropic.

PMID- 7806555
TI  - In vivo determination of the anatomical axes of the ankle joint complex: an
      optimization approach.
AB  - This study investigates the feasibility of a subject-specific three-dimensional
      model of the ankle joint complex for kinematic and dynamic analysis of movement.
      The ankle joint complex was modelled as a three-segment system, connected by two
      ideal hinge joints: the talocrural and the subtalar joint. A mathematical
      formulation was developed to express the three-dimensional translation and
      rotation between the foot and shank segments as a function of the two joint
      angles, and 12 model parameters describing the locations of the joint axes. An
      optimization method was used to fit the model parameters to three-dimensional
      kinematic data of foot and shank markers, obtained during test movements
      throughout the entire physiological range of motion of the ankle joint. The
      movement of the talus segment, which cannot be measured non-invasively, is not
      necessary for the analysis. This optimization method was used to determine the
      position and orientation of the joint axes in 14 normal subjects. After
      optimization, the discrepancy between the best fitting model and actual marker
      kinematics was between 1 and 3 mm for all subjects. The predicted inclination of
      the subtalar joint axis from the horizontal plane was 37.4 +/- 2.7 degrees, and
      the medial deviation was 18.0 +/- 16.2 degrees. The lateral side of the
      talucrural axis was directed slightly posteriorly (6.8 +/- 8.1 degrees), and
      inclined downward by 7.0 +/- 5.4 degrees. These results are similar to previously
      reported typical results from anatomical, in vitro studies. Reproducibility was
      evaluated by repeated testing of one subject, which resulted in variations of
      about one-fifth of the standard deviation within the group, the inclination of
      the subtalar joint axis was significantly correlated to the arch height and a
      radiographic 'tarsal index'. It is concluded that this optimization method
      provides the opportunity to incorporate inter-individual anatomical differences
      into kinematic and dynamic analysis of the ankle joint complex. This allows a
      more functional interpretation of kinematic data, and more realistic estimates of
      internal forces.

PMID- 7806556
TI  - Novel force transducer for the measurement of tendon force in vivo.

PMID- 7806557
TI  - Actin-related protein nomenclature and classification.

PMID- 7806558
TI  - Regulation of Dictyostelium myosin II by phosphorylation: what is essential and
      what is important?

PMID- 7806559
TI  - Scatter factor and the c-met receptor: a paradigm for mesenchymal/epithelial
      interaction.
AB  - Epithelia and mesenchyme interact during various physiologic and pathologic
      processes. Scatter factor is a mesenchyme-derived cytokine that stimulates
      motility, proliferation, and morphogenesis of epithelia. Recent studies suggest
      that scatter factor and its receptor (c-met) mediate mesenchyme/epithelia
      signalling and even interconversion. In this mini-review, we will discuss how
      scatter factor and c-met may mediate interactions between mesenchyme and
      epithelia during embryogenesis, organ repair, and neoplasia.

PMID- 7806560
TI  - Structurally divergent histone H1 variants in chromosomes containing highly
      condensed interphase chromatin.
AB  - Condensed and late-replicating interphase chromatin in the Dipertan insect
      Chironomus contains a divergent type of histone H1 with an inserted KAP-KAP
      repeat that is conserved in single H1 variants of Caenorhabditis elegans and
      Volvox carteri. H1 peptides comprising the insertion interact specifically with
      DNA. The Chironomid Glyptotendipes exhibits a corresponding correlation between
      the presence of condensed chromosome sections and the appearance of a divergent
      H1 subtype. The centromere regions and other sections of Glyptotendipes barbipes
      chromosomes are inaccessible to immunodecoration by anti-H2B and anti-H1
      antibodies one of which is known to recognize nine different epitopes in all
      domains of the H1 molecule. Microelectrophoresis of the histones from manually
      isolated unfixed centromeres revealed the presence of H1 and core histones. H1
      genes of G. barpipes were sequenced and found to belong to two groups. H1 II and
      H1 III are rather similar but differ remarkably from H1 I. About 30% of the
      deduced amino acid residues were found to be unique to H1 I. Most conspicuous is
      the insertion, SPAKSPGR, in H1 I that is lacking in H1 II and H1 III and at its
      position gives rise to the sequence repeat SPAKSPAKSPGR. The homologous H1 I gene
      in Glyptotendipes salinus encodes the very similar repeat TPAKSPAKSPGR. Both
      sequences are structurally related to the KAPKAP repeat in H1 I-1 specific for
      condensed chromosome sites in Chironomus and to the SPKKSPKK repeat in sea urchin
      sperm H1, lie at almost the same distance from the central globular domain, and
      could interact with linker DNA in packaging condensed chromatin.

PMID- 7806561
TI  - Yeast NOP2 encodes an essential nucleolar protein with homology to a human
      proliferation marker.
AB  - We have isolated a gene (NOP2) encoding a nucleolar protein during a search for
      previously unidentified nuclear proteins in the yeast Saccharomyces cerevisiae.
      The protein encoded by NOP2 (Nop2p) has a predicted molecular mass of 70 kD,
      migrates at 90 kD by SDS-PAGE, and is essential for cell viability. Nop2p shows
      significant amino acid sequence homology to a human proliferation-associated
      nucleolar protein, p120. Approximately half of Nop2p exhibits 67% amino acid
      sequence identity to p120. Analysis of subcellular fractions indicates that Nop2p
      is located primarily in the nucleus, and nuclear fractionation studies suggest
      that Nop2p is associated with the nucleolus. Indirect immunofluorescence
      localization of Nop2p shows a nucleolar-staining pattern, which is heterogeneous
      in appearance, and a faint staining of the cytoplasm. The expression of NOP2
      during the transition from stationary phase growth arrest to rapid growth was
      measured, and compared to the expression of TCM1, which encodes the ribosomal
      protein L3. Nop2p protein levels are markedly upregulated during the onset of
      growth, compared to the levels of ribosomal protein L3, which remain relatively
      constant. NOP2 mRNA levels also increase during the onset of growth, accompanied
      by a similar increase in the levels of TCM1 mRNA. The consequences of
      overexpressing NOP2 from the GAL10 promoter on a multicopy plasmid were
      investigated. Although NOP2 overexpression produced no discernible growth
      phenotype and had no effect on ribosome subunit synthesis, overexpression was
      found to influence the morphology of the nucleolus, as judged by electron
      microscopy. Overexpression caused the nucleolus to become detached from the
      nuclear envelope and to become more rounded and/or fragmented in appearance.
      These findings suggest roles for NOP2 in nucleolar function during the onset of
      growth, and in the maintenance of nucleolar structure.

PMID- 7806562
TI  - The G protein-activating peptide, mastoparan, and the synthetic NH2-terminal ARF
      peptide, ARFp13, inhibit in vitro Golgi transport by irreversibly damaging
      membranes.
AB  - Mastoparan is a cationic amphipathetic peptide that activates trimeric G
      proteins, and increases binding of the coat protein beta-COP to Golgi membranes.
      ARFp13 is a cationic amphipathic peptide that is a putative specific inhibitor of
      ARF function, and inhibits coat protein binding to Golgi membranes. Using a
      combination of high resolution, three-dimensional electron microscopy and cell
      free Golgi transport assays, we show that both of these peptides inhibit in vitro
      Golgi transport, not by interfering in the normal functioning of GTP-binding
      proteins, but by damaging membranes. Inhibition of transport is correlated with
      inhibition of nucleotide sugar uptake and protein glycoslation, a decrease in the
      fraction of Golgi cisternae exhibiting normal morphology, and a decrease in the
      density of Golgi-coated buds and vesicles. At peptide concentrations near the
      IC50 for transport, those cisternae with apparently normal morphology had a
      higher steady state level of coated buds and vesicles. Kinetic analysis suggests
      that this increase in density was due to a decrease in the rate of vesicle
      fission. Pertussis toxin treatment of the membranes appeared to increase the rate
      of vesicle formation, but did not prevent the membrane damage induced by
      mastoparan. We conclude that ARFp13 is not a specific inhibitor of ARF function,
      as originally proposed, and that surface active peptides, such as mastoparan,
      have the potential for introducing artifacts that complicate the analysis of
      trimeric G protein involvement in regulation of Golgi vesicle dynamics.

PMID- 7806564
TI  - The v-sis oncoprotein loses transforming activity when targeted to the early
      Golgi complex.
AB  - The location of autocrine interactions between the v-sis protein and PDGF
      receptors remains uncertain and controversial. To examine whether receptor-ligand
      interactions can occur intracellularly, we have constructed fusion proteins that
      anchor v-sis to specific intracellular membranes. Fusion of a cis-Golgi retention
      signal from a coronavirus E1 glycoprotein to v-sis protein completely abolished
      its transforming ability when transfected into NIH3T3 cells. Fusion proteins
      incorporating mutations in this retention signal were not retained within the
      Golgi complex but instead were transported to the cell surface, resulting in
      efficient transformation. All chimeric proteins were shown to dimerize properly.
      Derivatives of some of these constructs were also constructed bearing the
      cytoplasmic tail from the glycoprotein of vesicular stomatitis virus (VSV-G).
      These constructs allowed examination of subcellular localization by double-label
      immunofluorescence, using antibodies that distinguish between the extracellular
      PDGF-related domain and the VSV-G cytoplasmic tail. Colocalization of sis-E1-G
      with Golgi markers confirmed its targeting to the early Golgi complex. The sis-E1
      constructs, targeted to the early Golgi complex, exhibited no proteolytic
      processing whereas the mutant forms of sis-E1 exhibited normal proteolytic
      processing. Treatment with suramin, a polyanionic compound that disrupts
      ligand/receptor interactions at the cell surface, was able to revert the
      transformed phenotype induced by the mutant sis-E1 constructs described here. Our
      results demonstrate that autocrine interactions between the v-sis oncoprotein and
      PDGF receptors within the early Golgi complex do not result in functional signal
      transduction. Another v-sis fusion protein was constructed by attaching the
      transmembrane domain and COOH-terminus of TGN38, a protein that localizes to the
      trans-Golgi network (TGN). This construct was primarily retained intracellularly,
      although some of the fusion protein reached the surface. Deletion of the COOH
      terminal region of the TGN38 retention signal abrogated the TGN-localization, as
      evidenced by very prominent cell surface localization, and resulted in increased
      transforming activity. The behavior of the sis-TGN38 derivatives is discussed
      within the context of the properties of TGN38 itself, which is known to recycle
      from the cell surface to the TGN.

PMID- 7806563
TI  - Maturation of the trans-Golgi network protease furin: compartmentalization of
      propeptide removal, substrate cleavage, and COOH-terminal truncation.
AB  - We have cloned a bovine cDNA encoding the trans-Golgi network (TGN) protease
      furin and expressed it via recombinant vaccinia viruses to investigate
      intracellular maturation. Pulse-chase labeling reveals that the 104-kD pro-furin
      bearing high mannose N-glycans is rapidly processed into the 98-kD protease whose
      N-glycans remain sensitive to endoglycosidase H for a certain period of time.
      Furthermore, in the presence of brefeldin A, pro-furin cleavage occurs. From
      these data we conclude that the ER is the compartment of propeptide removal.
      Studies employing the ionophore A23187 and DTT show that autocatalysis is Ca2+
      dependent and that it does not occur under reducing conditions. Pro-furin
      produced under these conditions never gains endo H resistance indicating that it
      is retained in the ER. Coexpression of furin with the fowl plague virus
      hemagglutinin in the presence of brefeldin A and monensin reveals that furin has
      to enter the Golgi region to gain substrate cleaving activity. N-glycans of furin
      are sialylated proving its transit through the trans-Golgi network. A truncated
      form of furin is found in supernatants of cells. Truncation is inhibited in the
      absence of Ca2+ ions and in the presence of acidotropic agents indicating that it
      takes place in an acidic compartment of cells. Comparative analysis with furin
      expressed from cDNA reveals that the truncated form prevails in preparations of
      biologically active, endogenous furin obtained from MDBK cells. This observation
      supports the concept that secretion of truncated furin is a physiological event
      that may have important implications for the processing of extracellular
      substrates.

PMID- 7806565
TI  - Concentration of intracellular hepatic apolipoprotein E in Golgi apparatus
      saccular distensions and endosomes.
AB  - The intrahepatic distribution of apolipoprotein E has been assessed by immunogold
      labeling of cryosections as well as by Western blotting of organelles isolated
      from liver homogenates. Both techniques supported the prior analytical
      fractionation studies of Wong (1989) who concluded that intrahepatic apoE was
      largely endosomal. All endosomal components decorated by gold particles
      indicative of apoE antigenicity in cryosections appeared filled with lipoprotein
      like particles thereby accounting for this prominent morphological feature of
      isolated liver endosomes. The distribution of gold particles about the hepatic
      Golgi apparatus revealed a high content of apoE in closely apposed endosomes, ca.
      400 nm in diameter, double labeled for apoE and internalized HRP. Remarkably,
      apoE (but not internalized HRP) was also observed within saccular distensions of
      all saccules of stacked Golgi cisternae but absent from the flattened saccular
      components as was also observed for apoB. This contrasted with albumin, the major
      secretory protein, which was uniformly distributed throughout the hepatic Golgi
      apparatus. These observations support a growing body of evidence for intra-Golgi
      sorting of secretory material in hepatic Golgi apparatus. The lack of any
      immunoreactive apoE or albumin in small 70-90 nm vesicles about the Golgi
      cisternae suggests limits to current models of vesicle-mediated intra-Golgi
      transport.

PMID- 7806566
TI  - Isolation and characterization of the principal ATPase associated with
      transitional endoplasmic reticulum of rat liver.
AB  - The transfer of membranes from the endoplasmic reticulum to the Golgi apparatus
      occurs via 50-70 nm transition vesicles which derive from part-rough, part-smooth
      transitional elements of the endoplasmic reticulum (TER). Vesicle budding from
      the TER is an ATP-dependent process both in vivo and in vitro. An ATPase with a
      monomer molecular weight of 100 kD by SDS-PAGE has been isolated from TER and
      designated as TER ATPase. The native TER ATPase has been characterized as a
      hexamer of six 100-kD subunits by gel filtration. The protein catalyzes the
      hydrolysis of [gamma 32-P]ATP and is phosphorylated in the presence of Mg2+. It
      is distinct from the classical transport ATPases based on pH optima, ion effects,
      and inhibitor specificity. Electron microscopy of negatively stained preparations
      revealed the TER ATPase to be a ring-shaped structure with six-fold rotational
      symmetry. A 19-amino acid sequence of TER ATPase having 84% identity with valosin
      containing protein and 64% identity with a yeast cell-cycle control protein
      CDC48p was obtained. Anti-synthetic peptide antisera to a 15-amino acid portion
      of the sequence of TER ATPase recognized a 100-kD protein from TER. These
      antisera reduced the ATP-dependent cell-free formation of transition vesicles
      from isolated TER of rat liver. In a reconstituted membrane transfer system, TER
      ATPase antisera inhibited transfer of radiolabeled material from endoplasmic
      reticulum to Golgi apparatus, while preimmune sera did not. The results suggest
      that the TER ATPase is obligatorily involved in the ATP requirements for budding
      of transition vesicles from the TER. cDNA clones encoding TER ATPase were
      isolated by immunoscreening a rat liver cDNA library with the affinity-purified
      TER ATPase antibody. A computer search of deduced amino acid sequences revealed
      the cloned TER ATPase to be the rat equivalent of porcine valosin-containing
      protein, a member of a novel family of ATP binding, homo-oligomeric proteins
      including the N-ethylmaleimide-sensitive fusion protein.

PMID- 7806567
TI  - Restricted movement of lipid and aqueous dyes through pores formed by influenza
      hemagglutinin during cell fusion.
AB  - The fusion of cells by influenza hemagglutinin (HA) is the best characterized
      example of protein-mediated membrane fusion. In simultaneous measurements of
      pairs of assays for fusion, we determined the order of detectable events during
      fusion. Fusion pore formation in HA-triggered cell-cell fusion was first detected
      by changes in cell membrane capacitance, next by a flux of fluorescent lipid, and
      finally by flux of aqueous fluorescent dye. Fusion pore conductance increased by
      small steps. A retardation of lipid and aqueous dyes occurred during fusion pore
      fluctuations. The flux of aqueous dye depended on the size of the molecule. The
      lack of movement of aqueous dyes while total fusion pore conductance increased
      suggests that initial HA-triggered fusion events are characterized by the opening
      of multiple small pores: the formation of a "sieve".

PMID- 7806568
TI  - Analyzing phorbol ester effects on gap junctional communication: a dramatic
      inhibition of assembly.
AB  - The effect of 12-O-tetradeconylphorbol-13-acetate (TPA) on gap junction assembly
      between Novikoff hepatoma cells was examined. Cells were dissociated with EDTA to
      single cells and then reaggregated to form new junctions. When TPA (25 nM) was
      added to the cells at the onset of the 60-min reaggregation, dye transfer was
      detected at only 0.6% of the cell-cell interfaces compared to 72% for the
      untreated control and 74% for 4-alpha TPA, an inactive isomer of TPA. Freeze
      fracture electron microscopy of reaggregated control cells showed interfaces
      containing an average of more than 600 aggregated intramembranous gap junction
      particles, while TPA-treated cells had no gap junctions. However, Lucifer yellow
      dye transfer between nondissociated cells via gap junctions was unaffected by 60
      min of TPA treatment. Therefore, TPA dramatically inhibited gap junction assembly
      but did not alter channel gating nor enhance disassembly of preexisting gap
      junction structures. Short term TPA treatment (< 30 min) increased
      phosphorylation of the gap junction protein molecular weight of 43,000 (Cx43),
      but did not change the cellular level of Cx43. Cell surface biotinylation
      experiments suggested that TPA did not substantially reduce the plasma membrane
      concentration of Cx43. Therefore, the simple presence of Cx43 in the plasma
      membrane is not sufficient for gap junction assembly, and protein kinase C
      probably exerts an effect on assembly of gap junctions at the plasma membrane
      level.

PMID- 7806569
TI  - Cell-specific expression of epithelial sodium channel alpha, beta, and gamma
      subunits in aldosterone-responsive epithelia from the rat: localization by in
      situ hybridization and immunocytochemistry.
AB  - A highly selective, amiloride-sensitive, epithelial sodium channel from rat colon
      (rENaC), composed of three homologous subunits termed alpha, beta, and gamma
      rENaC, has been cloned by functional expression and was proposed to mediate
      electrogenic sodium reabsorption in aldosterone-responsive epithelia. To
      determine whether rENaC could account for sodium absorption in vivo, we studied
      the cellular localization of the sodium channel messenger RNA subunits by in situ
      hybridization and their cellular and subcellular distribution by
      immunocytochemistry in the kidney, colon, salivary, and sweat glands of the rat.
      In the kidney, we show that the three subunit mRNAs are specifically co-expressed
      in the renal distal convoluted tubules (DCT), connecting tubules (CNT), cortical
      collecting ducts (CCD), and outer medullary collecting ducts (OMCD), but not in
      the inner medullary collecting ducts (IMCD). We demonstrate co-localization of
      alpha, beta, and gamma subunit proteins in the apical membrane of a majority of
      cells of CCD and OMCD. Our data indicate that alpha, beta, and gamma subunit
      mRNAs and proteins are co-expressed in the distal nephron (excepting IMCD), a
      localization that correlates with the previously described physiological
      expression of amiloride-sensitive electrogenic sodium transport. Our data,
      however, suggest that another sodium transport protein mediates electrogenic
      amiloride-sensitive sodium reabsorption in IMCD. We also localized rENaC to the
      surface epithelial cells of the distal colon and to the secretory ducts of the
      salivary gland and sweat gland, providing further evidence consistent with the
      hypothesis that the highly selective, amiloride-sensitive sodium channel is
      physiologically expressed in aldosterone-responsive cells.

PMID- 7806570
TI  - Transient immunosuppressive treatment leads to long-term retention of allogeneic
      myoblasts in hybrid myofibers.
AB  - Normal and genetically engineered skeletal muscle cells (myoblasts) show promise
      as drug delivery vehicles and as therapeutic agents for treating muscle
      degeneration in muscular dystrophies. A limitation is the immune response of the
      host to the transplanted cells. Allogeneic myoblasts are rapidly rejected unless
      immunosuppressants are administered. However, continuous immunosuppression is
      associated with significant toxic side effects. Here we test whether
      immunosuppressive treatment, administered only transiently after allogeneic
      myoblast transplantation, allows the long-term survival of the transplanted cells
      in mice. Two immunosuppressive treatments with different modes of action were
      used: (a) cyclosporine A (CSA); and (b) monoclonal antibodies to intracellular
      adhesion molecule-1 and leukocyte function-associated molecule-1. The use of
      myoblasts genetically engineered to express beta-galactosidase allowed
      quantitation of the survival of allogeneic myoblasts at different times after
      cessation of the immunosuppressive treatments. Without host immunosuppression,
      allogeneic myoblasts were rejected from all host strains tested, although the
      relative time course differed as expected for low and high responder strains. The
      allogeneic myoblasts initially fused with host myofibers, but these hybrid cells
      were later destroyed by the massive immunological response of the host. However,
      transient immunosuppressive treatment prevented the hybrid myofiber destruction
      and led to their long-term retention. Even four months after the cessation of
      treatment, the hybrid myofibers persisted and no inflammatory infiltrate was
      present in the tissue. Such long-term survival indicates that transient
      immunosuppression may greatly increase the utility of myoblast transplantation as
      a therapeutic approach to the treatment of muscle and nonmuscle disease.

PMID- 7806571
TI  - Targeted disruption of the Dictyostelium RMLC gene produces cells defective in
      cytokinesis and development.
AB  - Conventional myosin has two different light chains bound to the neck region of
      the molecule. It has been suggested that the light chains contribute to myosin
      function by providing structural support to the neck region, therefore amplifying
      the conformational changes in the head following ATP hydrolysis (Rayment et al.,
      1993). The regulatory light chain is also believed to be important in regulating
      the actin-activated ATPase and myosin motor function as assayed by an in vitro
      motility assay (Griffith et al., 1987). Despite extensive in vitro biochemical
      study, little is known regarding RMLC function and its regulatory role in vivo.
      To better understand the importance and contribution of RMLC in vivo, we
      engineered Dictyostelium cell lines with a disrupted RMLC gene. Homologous
      recombination between the introduced gene disruption vector and the chromosomal
      RMLC locus (mlcR) resulted in disruption of the RMLC-coding region, leading to
      cells devoid of both the RMLC transcript and the 18-kD RMLC polypeptide. RMLC
      deficient cells failed to divide in suspension, becoming large and multinucleate,
      and could not complete development following starvation. These results, similar
      to those from myosin heavy chain mutants (DeLozanne et al., 1987; Manstein et
      al., 1989), suggest the RMLC subunit is required for normal cytokinesis and cell
      motility. In contrast to the myosin heavy chain mutants, however, the mlcR cells
      are able to cap cell surface receptors following concanavilin A treatment. By
      immunofluorescence microscopy, RMLC null cells exhibited myosin localization
      patterns different from that of wild-type cells. The myosin localization in RMLC
      null cells also varied depending upon whether the cells were cultured in
      suspension or on a solid substrate. In vitro, purified RMLC- myosin assembled to
      form thick filaments comparable to wild-type myosin, but the filaments then
      exhibit abnormal disassembly properties. These results indicate that in vivo RMLC
      is necessary for myosin function.

PMID- 7806573
TI  - Traction forces generated by locomoting keratocytes.
AB  - Traction forces produced by moving fibroblasts have been observed as distortions
      in flexible substrata including wrinkling of thin, silicone rubber films.
      Traction forces generated by fibroblast lamellae were thought to represent the
      forces required to move the cell forwards. However, traction forces could not be
      detected with faster moving cell types such as leukocytes and growth cones
      (Harris, A. K., D. Stopak, and P. Wild. 1981. Nature (Lond.). 290:249-251). We
      have developed a new assay in which traction forces produced by rapidly
      locomoting fish keratocytes can be detected by the two-dimensional displacements
      of small beads embedded in the plane of an elastic substratum. Traction forces
      were not detected at the rapidly extending front edge of the cell. Instead the
      largest traction forces were exerted perpendicular to the left and right cell
      margins. The maximum traction forces exerted by keratocytes were estimated to be
      approximately 2 x 10(-8) N. The pattern of traction forces can be related to the
      locomotion of a single keratocyte in terms of lamellar contractility and area of
      close cell-substratum contact.

PMID- 7806572
TI  - Expression of a myosin regulatory light chain phosphorylation site mutant
      complements the cytokinesis and developmental defects of Dictyostelium RMLC null
      cells.
AB  - In a number of systems phosphorylation of the regulatory light chain (RMLC) of
      myosin regulates the activity of myosin. In smooth muscle and vertebrate
      nonmuscle systems RMLC phosphorylation is required for contractile activity. In
      Dictyostelium discoideum phosphorylation of the RMLC regulates both ATPase
      activity and motor function. We have determined the site of phosphorylation on
      the Dictyostelium RMLC and used site-directed mutagenesis to replace the
      phosphorylated serine with an alanine. The mutant light chain was then expressed
      in RMLC null Dictyostelium cells (mLCR-) from an actin promoter on an integrating
      vector. The mutant RMLC was expressed at high levels and associated with the
      myosin heavy chain. RMLC bearing a ser13ala substitution was not phosphorylated
      in vitro by purified myosin light chain kinase, nor could phosphate be detected
      on the mutant RMLC in vivo. The mutant myosin had reduced actin-activated ATPase
      activity, comparable to fully dephosphorylated myosin. Unexpectedly, expression
      of the mutant RMLC rescued the primary phenotypic defects of the mlcR- cells to
      the same extent as did expression of wild-type RMLC. These results suggest that
      while phosphorylation of the Dictyostelium RMLC appears to be tightly regulated
      in vivo, it is not essential for myosin-dependent cellular functions.

PMID- 7806574
TI  - Direct visualization of the microtubule lattice seam both in vitro and in vivo.
AB  - Microtubules are constructed from alpha- and beta-tubulin heterodimers that are
      arranged into protofilaments. Most commonly there are 13 or 14 protofilaments. A
      series of structural investigations using both electron microscopy and x-ray
      diffraction have indicated that there are two potential lattices (A and B) in
      which the tubulin subunits can be arranged. Electron microscopy has shown that
      kinesin heads, which bind only to beta-tubulin, follow a helical path with a 12
      nm pitch in which subunits repeat every 8-nm axially, implying a primarily B-type
      lattice. However, these helical symmetry parameters are not consistent with a
      closed lattice and imply that there must be a discontinuity or "seam" along the
      microtubule. We have used quick-freeze deep-etch electron microscopy to obtain
      the first direct evidence for the presence of this seam in microtubules formed
      either in vivo or in vitro. In addition to a conventional single seam, we have
      also rarely found microtubules in which there is more than one seam. Overall our
      data indicates that microtubules have a predominantly B lattice, but that A
      lattice bonds between tubulin subunits are found at the seam. The cytoplasmic
      microtubules in mouse nerve cells also have predominantly B lattice structure and
      A lattice bonds at the seam. These observations have important implications for
      the interaction of microtubules with MAPs and with motor proteins, and for
      example, suggest that kinesin motors may follow a single protofilament track.

PMID- 7806575
TI  - STU1, a suppressor of a beta-tubulin mutation, encodes a novel and essential
      component of the yeast mitotic spindle.
AB  - We have isolated a cold-sensitive allele of TUB2, the sole gene encoding beta
      tubulin in S. cerevisiae, that confers a specific defect in spindle microtubule
      function. At 14 degrees C, tub2-406 cells lack a normal bipolar spindle but do
      assemble functional cytoplasmic microtubules. In an attempt to identify proteins
      that are important for spindle assembly, we screened for suppressors of the cold
      sensitivity of tub2-406 and obtained four alleles of a novel gene, STU1. Genetic
      interactions between stu1 alleles and alleles of TUB1 and TUB2 suggest that Stu1p
      specifically interacts with microtubules. STU1 is essential for growth and
      disruption of STU1 causes defects in spindle assembly that are similar to those
      produced by the tub2-406 mutation. The nucleotide sequence of the STU1 gene
      predicts a protein product of 174 kD with no significant similarity to known
      proteins. An epitope-tagged Stulp colocalizes with microtubules in the mitotic
      spindle of yeast. These results demonstrate that Stulp is an essential component
      of the yeast mitotic spindle.

PMID- 7806576
TI  - Daughter cells of Saccharomyces cerevisiae from old mothers display a reduced
      life span.
AB  - The yeast Saccharomyces cerevisiae typically divides asymmetrically to give a
      large mother cell and a smaller daughter cell. As mother cells become old, they
      enlarge and produce daughter cells that are larger than daughters derived from
      young mother cells. We found that occasional daughter cells were
      indistinguishable in size from their mothers, giving rise to a symmetric
      division. The frequency of symmetric divisions became greater as mother cells
      aged and reached a maximum occurrence of 30% in mothers undergoing their last
      cell division. Symmetric divisions occurred similarly in rad9 and ste12 mutants.
      Strikingly, daughters from old mothers, whether they arose from symmetric
      divisions or not, displayed reduced life spans relative to daughters from young
      mothers. Because daughters from old mothers were larger than daughters from young
      mothers, we investigated whether an increased size per se shortened life span and
      found that it did not. These findings are consistent with a model for aging that
      invokes a senescence substance which accumulates in old mother cells and is
      inherited by their daughters.

PMID- 7806577
TI  - Functional differences between L- and T-plastin isoforms.
AB  - Fimbrins/plastins are a family of highly conserved actin-bundling proteins. They
      are present in all eukaryotic cells including yeast, but each isoform displays a
      remarkable tissue specificity. T-plastin is normally found in epithelial and
      mesenchymal cells while L-plastin is present in hematopoietic cells. However, L
      plastin has been also found in tumor cells of non-hematopoietic origin (Lin, C.
      S., R. H. Aebersold, S. B. Kent, M. Varma, and J. Leavitt. 1988. Mol. Cell. Biol.
      8:4659-4668; Lin, C.-S., R. H. Aebersold, and J. Leavitt. 1990. Mol. Cell. Biol.
      10: 1818-1821). To learn more about the biological significance of their tissue
      specificity, we have overproduced the T- and L-plastin isoforms in a fibroblast
      like cell line, CV-1, and in a polarized epithelial cell line, LLC-PK1. In CV-1
      cells, overproduction of T- and L-plastins induces cell rounding and a
      concomitant reorganization of actin stress fibers into geodesic structures. L
      plastin remains associated with microfilaments while T-plastin is almost
      completely extracted after treatment of the cells with non-ionic detergent. In
      LLC-PK1 cells, T-plastin induces shape changes in microvilli and remains
      associated with microvillar actin filaments after detergent extraction while L
      plastin has no effect on these structures and is completely extracted. The effect
      of T-plastin on the organization of microvilli differs from that of villin,
      another actin-bundling protein. Our experiments indicate that these two isoforms
      play differing roles in actin filament organization, and do so in a cell type
      specific fashion. Thus it is likely that these plastin isoforms play
      fundamentally different roles in cell function.

PMID- 7806578
TI  - Neogenin, an avian cell surface protein expressed during terminal neuronal
      differentiation, is closely related to the human tumor suppressor molecule
      deleted in colorectal cancer.
AB  - Using a monoclonal antibody, we have identified and characterized a previously
      unknown cell surface protein in chicken that we call neogenin and have determined
      its primary sequence. The deduced amino acid sequence and structure of neogenin
      characterize it as a member of the immunoglobulin (Ig) superfamily. Based on
      amino acid sequence similarities, neogenin is closely related to the human tumor
      suppressor molecule DCC (deleted in colorectal cancer). Neogenin and DCC define a
      subgroup of Ig superfamily proteins structurally distinct from other Ig molecules
      such as N-CAM, Ng-CAM, and Bravo/Nr-CAM. As revealed by antibody staining of
      tissue sections and Western blots, neogenin expression correlates with the onset
      of neuronal differentiation. Neogenin is also found on cells in the lower
      gastrointestinal tract of embryonic chickens. DCC has been observed in human
      neural tissues and has been shown to be essential for terminal differentiation of
      specific cell types in the adult human colon. These parallels suggest that
      neogenin, like DCC, is functionally involved in the transition from cell
      proliferation to terminal differentiation of specific cell types. Since neogenin
      is expressed on growing neurites and downregulated at termination of neurite
      growth, it may also play an important role in many of the complex functional
      aspects of neurite extension and intercellular signaling.

PMID- 7806579
TI  - TGF-beta induced transdifferentiation of mammary epithelial cells to mesenchymal
      cells: involvement of type I receptors.
AB  - The secreted polypeptide transforming growth factor-beta (TGF-beta) exerts its
      multiple activities through type I and II cell surface receptors. In epithelial
      cells, activation of the TGF-beta signal transduction pathways leads to
      inhibition of cell proliferation and an increase in extracellular matrix
      production. TGF-beta is widely expressed during development and its biological
      activity has been implicated in epithelial-mesenchymal interactions, e.g., in
      branching morphogenesis of the lung, kidney, and mammary gland, and in inductive
      events between mammary epithelium and stroma. In the present study, we
      investigated the effects of TGF-beta on mouse mammary epithelial cells in vitro.
      TGF-beta reversibly induced an alteration in the differentiation of normal
      mammary epithelial NMuMG cells from epithelial to fibroblastic phenotype. The
      change in cell morphology correlated with (a) decreased expression of the
      epithelial markers E-cadherin, ZO-1, and desmoplakin I and II; (b) increased
      expression of mesenchymal markers, such as fibronectin; and (c) a fibroblast-like
      reorganization of actin fibers. This phenotypic differentiation displays the
      hallmarks of an epithelial to mesenchymal transdifferentiation event. Since NMuMG
      cells make high levels of the type I TGF-beta receptor Tsk7L, yet lack expression
      of the ALK-5/R4 type I receptor which has been reported to mediate TGF-beta
      responsiveness, we evaluated the role of the Tsk7L receptor in TGF-beta-mediated
      transdifferentiation. We generated NMuMG cells that stably overexpress a
      truncated Tsk7L type I receptor that lacks most of the cytoplasmic kinase domain,
      thus function as a dominant negative mutant. These transfected cells no longer
      underwent epithelial to mesenchymal morphological change upon exposure to TGF
      beta, yet still displayed some TGF-beta-mediated responses. We conclude that TGF
      beta has the ability to modulate E-cadherin expression and induce a reversible
      epithelial to mesenchymal transdifferentiation in epithelial cells. Unlike other
      transdifferentiating growth factors, such as bFGF and HGF, these changes are
      accompanied by growth inhibition. Our results also implicate the Tsk7L type I
      receptor as mediating the TGF-beta-induced epithelial to mesenchymal transition.

PMID- 7806580
TI  - Expression of variant fibronectins in wound healing: cellular source and
      biological activity of the EIIIA segment in rat hepatic fibrogenesis.
AB  - We have examined the cell-specific expression of two fibronectin isoforms, EIIIA
      and EIIIB, during experimental hepatic fibrosis induced by ligation of the
      biliary duct. AT the mRNA level, EIIIA and EIIIB were undetectable in normal
      liver but expressed early injury, preceding fibrosis. The cellular sources of
      these changes were determined by fractionating the liver at various time points
      after bile duct ligation into its constituent cell populations and extracting RNA
      from the fresh isolates. EIIIA-containing fibronectin mRNA was undetectable in
      normal sinusoidal endothelial cells but increased rapidly within 12 h of injury.
      By contrast, the EIIIB form was restricted to hepatic lipocytes (Ito or fat
      storing cells) and appeared only after a lag of 12-24 h: it was minimal in
      sinusoidal endothelial cells. Both forms were minimal in hepatocytes. At the
      protein level, EIIIA-containing fibronectin was markedly increased within two
      days of injury and exhibited a sinusoidal distribution. Secretion of this form by
      endothelial cells was confirmed in primary culture. Matrices deposited in situ by
      endothelial cells from injured liver accelerated the conversion ("activation") of
      normal lipocytes to myofibroblast-like cells, and pretreatment of matrices with
      monoclonal antibody to the EIIIA segment blocked this response. Finally,
      recombinant fibronectin peptide containing the EIIIA segment was stimulatory to
      lipocytes in culture. We conclude that expression of EIIIA fibronectin by
      sinusoidal endothelial cells is a critical early event in the liver's response to
      injury and that the EIIIA segment is biologically active, mediating the
      conversion of lipocytes to myofibroblasts.

PMID- 7806581
TI  - Measurements of growth cone adhesion to culture surfaces by micromanipulation.
AB  - Neurons were grown on plastic surfaces that were untreated, or treated with
      polylysine, laminin, or L1 and their growth cones were detached from their
      culture surface by applying known forces with calibrated glass needles. This
      detachment force was taken as a measure of the force of adhesion of the growth
      cone. We find that on all surfaces, lamellipodial growth cones require
      significantly greater detachment force than filopodial growth cones, but this
      differences is, in general, due to the greater area of lamellipodial growth cones
      compared to filopodial growth cones. That is, the stress (force/unit area)
      required for detachment was similar for growth cones of lamellipodial and
      filopodial morphology on all surfaces, with the exception of lamellipodial growth
      cones on L1-treated surfaces, which had a significantly lower stress of
      detachment than on other surfaces. Surprisingly, the forces required for
      detachment (760-3,340 mudynes) were three to 15 times greater than the typical
      resting axonal tension, the force exerted by advancing growth cones, or the
      forces of retraction previously measured by essentially the same method. Nor did
      we observe significant differences in detachment force among growth cones of
      similar morphology on different culture surfaces, with the exception of
      lamellipodial growth cones on L1-treated surfaces. These data argue against the
      differential adhesion mechanism for growth cone guidance preferences in culture.
      Our micromanipulations revealed that the most mechanically resistant regions of
      growth cone attachment were confined to quite small regions typically located at
      the ends of filopodia and lamellipodia. Detached growth cones remained connected
      to the substratum at these regions by highly elastic retraction fibers. The
      closeness of contact of growth cones to the substratum as revealed by
      interference reflection microscopy (IRM) did not correlate with our mechanical
      measurements of adhesion, suggesting that IRM cannot be used as a reliable
      estimator of growth cone adhesion.

PMID- 7806582
TI  - E-cadherin and APC compete for the interaction with beta-catenin and the
      cytoskeleton.
AB  - beta-Catenin is involved in the formation of adherens junctions of mammalian
      epithelia. It interacts with the cell adhesion molecule E-cadherin and also with
      the tumor suppressor gene product APC, and the Drosophila homologue of beta
      catenin, armadillo, mediates morphogenetic signals. We demonstrate here that E
      cadherin and APC directly compete for binding to the internal, armadillo-like
      repeats of beta-catenin; the NH2-terminal domain of beta-catenin mediates the
      interaction of the alternative E-cadherin and APC complexes to the cytoskeleton
      by binding to alpha-catenin. Plakoglobin (gamma-catenin), which is structurally
      related to beta-catenin, mediates identical interactions. We thus show that the
      APC tumor suppressor gene product forms strikingly similar associations as found
      in cell junctions and suggest that beta-catenin and plakoglobin are central
      regulators of cell adhesion, cytoskeletal interaction, and tumor suppression.

PMID- 7806583
TI  - Orthotopic is orthodox: why are orthotopic-transplant metastatic models different
      from all other models?

PMID- 7806584
TI  - Aluminum-induced DNA synthesis in osteoblasts: mediation by a G-protein coupled
      cation sensing mechanism.
AB  - Aluminum (Al3+) stimulates de novo bone formation in dogs and is a potent
      stimulus for DNA synthesis in non-transformed osteoblasts in vitro. The recent
      identification of a G-protein coupled cation-sensing receptor (BoPCaR), which is
      activated by polyvalent agonists [e.g., gadolinium (Gd3+) > neomycin > calcium
      (Ca2+)], suggests that a similar physiologically important cation sensing
      receptor may be present in osteoblasts and pharmacologically activated by Al3+.
      To evaluate that possibility, we assessed whether known BoPCaR agonists stimulate
      DNA synthesis in MC3T3-E1 osteoblasts and examined the additive effects of Al3+
      and BoPCaR agonists on DNA synthesis in MC3T3-E1 osteoblast-like cells. We found
      that Al3+, Gd3+, neomycin, and Ca2+ stimulated DNA synthesis in a dose-dependent
      fashion, achieving 50% effective extracellular concentrations (EC50) of 10
      microM, 30 microM, 60 microM, and 2.5 mM, respectively. Al3+ displayed non
      additive effects on DNA synthesis with the BoPCaR agonists as well as an
      unrelated G-protein coupled receptor agonist, PGF2 alpha, suggesting shared
      mechanisms of action. In contrast, the receptor tyrosine kinase agonist, IGF-I
      (10 eta g/ml), displayed additive proliferative effects when combined with AlCl3,
      indicating distinct signalling pathways. AlCl3 (25 microM) induced DAG levels 2
      fold and the phosphorylation of the myristoylated alanine-rich C kinase (MARCKS)
      substrate 4-fold, but did not increase intracellular calcium concentrations. Down
      regulation of PKC by pre-treatment with phorbol 12-myristate 13-acetate as well
      as PKC inhibition by H-7 and staurosporine blocked Al(3+)-induced DNA synthesis.
      Finally, Al3+, Gd3+, neomycin, and Ca2+ activated G-proteins in osteoblast
      membranes as evidenced by increased covalent binding of [32P]-GTP-azidoanilide to
      putative G alpha subunits. Our findings suggest that Al3+ stimulates DNA
      synthesis in osteoblasts through a cation sensing mechanism coupled to G-protein
      activation and signalling cascades involving DAG and PKC-dependent pathways.

PMID- 7806585
TI  - Inhibition of bone resorption by selective inactivators of cysteine proteinases.
AB  - Inactivators of cysteine proteinases (CPs) were tested as inhibitors of bone
      resorption in vitro and in vivo. The following four CP inactivators were tested:
      Ep475, a compound with low membrane permeability which inhibits cathepsins B, L,
      S, H, and calpain; Ep453, the membrane-permeant prodrug of Ep475; CA074, a
      compound with low membrane permeability which selectively inactivates cathepsin
      B; and CA074Me, the membrane-permeant prodrug of CA074. The test systems
      consisted of 1) monitoring the release of radioisotope from prelabelled mouse
      calvarial explants and 2) assessing the extent of bone resorption in an isolated
      osteoclast assay using confocal laser microscopy. Ep453, Ep475, and CA074Me
      inhibited both stimulated and basal bone resorption in vitro while CA074 was
      without effect; the inhibition was reversible and dose dependent. None of the
      inhibitors affected protein synthesis, DNA synthesis, the PTH-enhanced secretion
      of beta-glucuronidase, and N-acetyl-beta-glucosaminidase, or the spontaneous
      release of lactate dehydrogenase. Ep453, Ep475, and CA074Me dose-dependently
      inhibited the resorptive activity of isolated rat osteoclasts cultured on bone
      slices with a maximal effect at 50 microM. The number of resorption pits and
      their mean volume was reduced, whilst the mean surface area remained unaffected.
      Again, CA074 was without effect. Ep453, Ep475, and CA074Me, but not CA074, when
      administered subcutaneously at a dose of 60 micrograms/g body weight inhibited
      bone resorption in vivo as measured by an in vivo/in vitro assay, by about 20%.
      This study demonstrates that cathepsins B, L, and/or S are involved in bone
      resorption in vitro and in vivo. Whilst cathepsin L and/or S act extracellularly,
      and possibly intracellularly, cathepsin B mediates its effects intracellularly
      perhaps through the activation of other proteinases involved in subosteoclastic
      collagen degradation.

PMID- 7806586
TI  - Tyrosine dephosphorylation and concurrent inactivation of protein kinase FA/GSK-3
      alpha by genistein in A431 cells.
AB  - Modulation of protein kinase FA/GSK-3 alpha by tyrosine phosphorylation in A431
      cells was investigated. Kinase FA/GSK-3 alpha was found to exist in a highly
      tyrosine-phosphorylated/activated state in resting cells but could become
      tyrosine-dephosphorylated and inactivated down to less than 30% of control values
      in a concentration-dependent manner by 50-400 microM genistein (a specific
      tyrosine kinase inhibitor), as demonstrated by metabolic 32P-labeling of the
      cells followed by immunoprecipitation and two-dimensional phosphoamino acid
      analysis and by immunodetection in an antikinase FA/GSK-3 alpha immunoprecipitate
      kinase assay. Taken together, the results provide evidence that kinase FA/GSK-3
      alpha may exist in a highly tyrosine-phosphorylated/activated state in resting
      cells which can be tyrosine-dephosphorylated and inactivated by extracellular
      stimulus and that tyrosine kinase(s) and/or tyrosine phosphatase(s) may play a
      role in the modulation of kinase FA/GSK-3 alpha activity in cells.

PMID- 7806587
TI  - Analyzing the metastatic phenotype.
AB  - The dissemination of cells from a primary tumor, resulting in the progressive
      growth of metastatic carcinoma in distant sites, is the most common cause of
      death of cancer patients. The observations from clinical studies and the results
      of experimental studies using rodent tumors and human cancer cells implanted into
      immunodeficient host animals suggest that metastasis is not a random event, but
      rather the result of a sequence of selective events, many of which involve
      interactions with elements of the microenvironment of the primary and metastatic
      tumors. Analysis of the metastatic potential of a human tumor cell population has
      been greatly improved by the introduction of orthotopic models of tumor growth
      and metastasis, which have demonstrated that implanting human tumor cells into
      the appropriate tissue in an immunodeficient rodent can increase both tumor take
      and incidence of metastasis. These will be the models that should be used to
      validate the identity of candidate metastasis-associated genes, and to determine
      the value of new forms of therapy, either genetic or pharmacological, for
      controlling metastatic cancer growth.

PMID- 7806588
TI  - Microenvironment revisited: time for reappraisal of some prevailing concepts of
      cancer metastasis.
AB  - The development and biological characteristics of tumor metastasis are influenced
      by multiple cell and host-associated factors. To study these factors
      experimentally, the necessity of choosing adequate in vivo model systems for
      human tumor metastasis is emphasized. Recent research has provided results that
      highlight the role of the microenvironment in determining important
      characteristics of the metastatic cells, including their degree of
      differentiation and sensitivity to drugs. Furthermore, evidence is presented as
      background for discussing the general validity of the notion of clonal selection
      of metastatic cells, and whether the metastatic phenotype is acquired through the
      last of a series of mutational events occurring during tumor progression.

PMID- 7806589
TI  - Exploring processes of organization of normal and neoplastic epithelial tissues
      in gradient culture.
AB  - The biology of animal cells in culture is often studied in individual cells or in
      sheets of cells. The relevance of such studies to the intact animal is unclear,
      since the spatial conditions encountered by cells in animals is one of dense
      three-dimensional masses of cells, with limits to migration, and with gradients
      both of diffusion of metabolites and of morphologic maturation. These spatial
      requisites have gradually been met in culture. A brief account describes sponge
      matrix culture for three-dimensional growth and unilaminar, bilaminar, and radial
      histophysiologic gradient cultures. Some of the common neoplastic abnormalities
      of surface epithelial tissues are considered. Proposals for investigating the
      histokinetic mechanisms regulating some epithelial tissue processes are
      suggested. In the most recent development of gradient culture methods, a thin
      permeable transparent collagen membrane is intrinsically strengthened by
      producing a waffle membrane pattern for histophysiologic gradient culture.

PMID- 7806590
TI  - Intrinsic or acquired drug resistance and metastasis: are they linked phenotypes?
AB  - Evidence is reviewed which suggests a linkage may exist between certain forms of
      de novo or acquired drug resistance and metastasis. This includes the finding
      that expression of certain dominantly acting mutant oncogenes or tumor suppressor
      genes, i.e., genes which normally act to "drive" tumor progression and
      metastasis, can also affect the expression of drug resistance. Moreover, this can
      be accompanied by altered expression of certain cellular genes thought to be
      involved in expression of drug resistance. A direct linkage between acquired drug
      resistance and metastasis would suggest that tumor sublines selected for drug
      resistance should manifest more aggressive malignant properties than their drug
      sensitive counterparts. While this does not appear to be true for drug resistant
      sublines selected in vitro, indeed such cell lines frequently manifest diminished
      in vivo tumorigenic and/or metastatic competence, there is some evidence to
      support such a correlation exists for tumor cell lines that are selected in vivo
      for drug resistance. Attention is also drawn to the fact that new linkages
      between metastasis and drug resistance may be uncovered by analyzing the ability
      of tumor subpopulations to acquire drug resistance after one or several previous
      exposures to chemotherapeutic drugs, as opposed to examining intrinsic drug
      resistance only. Furthermore, ability to detect induced or acquired drug
      resistance in vitro may be strongly influenced by the types of assay used to
      detect and monitor drug resistance. In particular, three-dimensional cell culture
      systems may reveal acquired or induced "multicellular" drug resistance in
      situations where conventional two-dimensional culture systems do not. Use of
      three-dimensional culture systems may therefore reveal as yet undiscovered
      associations between the phenotypes of metastasis and drug resistance.

PMID- 7806591
TI  - Metastatic models of human cancer xenografted in the nude mouse: the importance
      of orthotopic transplantation.
AB  - Metastatic model of human tumor xenografts have been developed using orthotopic
      transplantation of histologically intact tissue (onplantation) of lung, stomach,
      colon, pancreatic, prostate and bladder carcinomas. These models represent the
      entire process of the metastasis, consisting of local tumor growth, vascular and
      lymphatic invasion at the local site, flow in the vessels and lymphatic,
      extravasation at the metastatic organs, and seeding and growth at relevant
      metastatic sites. Orthotopically transplanted human small-cell lung carcinoma
      displayed a different chemosensitivity pattern compared with the subcutaneous
      transplanted model, suggesting different pharmacodynamics between the orthotopic
      lung and the ectopic subcutaneous sites. The intact-tissue orthotopic
      onplantation model seems to be useful to study the mechanism of metastasis for
      discovery of antimetastatic agents and for the patient tumors and for this
      treatment design.

PMID- 7806592
TI  - Rationale for using TNF alpha and chemotherapy in regional therapy of melanoma.
AB  - Recombinant tumor necrosis factor-alpha (rTNF alpha) has potent antitumor
      activity in experimental studies on human tumor xenografts. However, in humans,
      the administration of rTNF alpha is hampered by severe systemic side-effects. The
      maximum tolerated dose ranges from 350 to 500 mg/m2, which is at least 10-fold
      less than the efficient dose in animals. Isolation perfusion of the limbs (ILP)
      allows the delivery of high dose rTNF alpha in a closed system with acceptable
      side-effects. A protocol with triple-drug regimen was based on the reported
      synergism of rTNF alpha with chemotherapy, with interferon-gamma, and with
      hyperthermia. In melanoma-in-transit metastases (stage IIIA or AB) we obtained a
      91% complete response, compared with 52% after ILP with melphalan alone. Release
      of nanograms levels of TNF alpha in the systemic circulation was evident but
      control of this leakage and appropriate intensive care resulted in acceptable
      toxicity. Angiographic, immunohistological, and immunological studies suggest
      that the efficacy of this protocol is due to a dual targeting: rTNF alpha
      activates and electively lyses the tumor endothelial cells while melphalan is
      mainly cytotoxic to the tumor cells. ILP with rTNF alpha appears to be a useful
      model for studying the biochemotherapy of cancer in man.

PMID- 7806593
TI  - A complex composed of at least two HeLa nuclear proteins protects preferentially
      one DNA strand of the simple (gt)n(ga)m containing region of intron 2 in HLA-DRB
      genes.
AB  - Electrophoretic mobility shift assays reveal that HeLa nuclear proteins bind fast
      and with measurable affinity to target DNAs containing mixed simple repetitive
      (gt)n(ga)m stretches. Preincubation of the proteins at elevated temperature
      prevents the formation of the major DNA/protein complex in favour of several
      distinct assemblies. A similar pattern of retarded bands was observed employing
      higher salt concentrations in the binding reaction. Thus conformational changes
      of different proteins appear to influence the complex rather than alternating DNA
      structures. Separation of the total nuclear extract into a water soluble and an
      insoluble protein fraction leads to a complete loss of target DNA binding
      capability of the fractions. The binding capacity is restored by combining the
      two fractions suggesting that at least two protein components are necessary to
      form a complex with the target sequence. The proteins can be differentiated into
      heat sensitive, water soluble and temperature stable, water insoluble,
      respectively. Furthermore, specifically binding polypeptides are not detectable
      by Southwestern analyses, probably because the essential components are separated
      during electrophoresis. DNase I footprint analyses yield four different protein
      binding regions only on the (gt)n(ga)m harbouring strand. The footprints cover
      larger portions of the mixed simple repeat in addition to a portion 5' of the
      (gt)n part. Hence at least two nuclear protein components of unknown biological
      function have to be present simultaneously to protect preferentially the
      (gt)n(ga)m-containing strand of intron 2 in HLA-DRB genes.

PMID- 7806594
TI  - Human breast and colon cancers exhibit alterations of DNA methylation patterns at
      several DNA segments on chromosomes 11p and 17p.
AB  - In breast and colon adenocarcinomas methylation patterns at CCGG sites of several
      loci located on the short arm of chromosome 11 were determined by Southern blot
      analysis. Results obtained indicate that all tumor samples (20/20) exhibit DNA
      methylation changes when compared to their normal counterparts. In colon tumors,
      gamma-globin gene is usually hypomethylated (9/10), whereas Ha-ras gene, which is
      located in the same region, retains an unmodified DNA methylation pattern.
      Hypomethylation of parathyroid hormone (5/10) and catalase genes (4/10) are also
      frequently detected in colon tumor specimens. For the catalase gene the region
      around exon 2 is the only one which is affected by these changes. In breast
      adenocarcinoma, modifications of the methylation patterns are less frequently
      observed. However, hypomethylation of the gamma-globin gene is a very common
      event in these tumors (8/10), and it is also detected (2/2) in lobular carcinoma
      in situ which is an early step in breast tumorigenesis. In addition,
      hypermethylation of a CpG island is also observed at the locus 17p13.3 in both
      colon (5/5) and breast (4/9) adenocarcinomas. In the tumoral tissues analyzed
      these hypermethylations are not associated with the hypermethylation of the 5'
      flanking sequences which contain a limited amount of CpG. Some of these
      alterations seem, therefore, to be tumor and sequence specific.

PMID- 7806595
TI  - "Patient-like" nude mouse metastatic model of advanced human pleural cancer.
AB  - Pleural cancer in humans is a frequently occurring tumor. Recently, clinical
      trials have suggested that chemotherapy and immunotherapy administered
      intrapleurally may elicit responses in early-stage diseases. However, at
      radiological and pleural endoscopic evaluation, most of the patients are found to
      have a visceral pleural involvement that is generally refractory to therapy and
      leads to a poor prognosis. The goal of this study was to construct a nude mouse
      model of human parietal- and visceral-pleural cancer that could reflect the
      clinical picture for this disease. The model could then be useful for drug
      discovery for pleural cancer. A well-differentiated human lung adenocarcinoma was
      used as intact tissue for implantation. Ten mice underwent parietal-pleural
      implantation and ten mice visceral-pleural implantation via a novel thoracotomy
      procedure we have developed. Symptoms of tumor growth were determined from weight
      loss, respiratory distress, or debilitation. Actual tumor growth and spread were
      measured at autopsy. The mouse survival curves of each group were estimated by
      the Kaplan-Meier method and the difference of the median survival times was
      assessed by the Log-rank test. The slopes of mean-mouse weight curves were
      compared using a standard two-sample t-test. A 100% take rate was achieved in
      constructing the pleural cancer models. Tumor growth was initially assessed by
      symptomatology and survival: the median survival time was, respectively, 27.9
      days and 31 days for visceral-pleural and parietal-pleural implanted groups (P <
      0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7806596
TI  - Purification and characterization of two collagenase inhibitors from mouse
      sarcoma 180 conditioned medium.
AB  - We have previously shown that mouse sarcoma 180 cells produce vascular
      endothelial growth factor [VEGF; Rosenthal et al., 1990, Growth Factors, 4: 53
      59], an endothelial mitogen that stimulates angiogenesis. Recent reports have
      implicated metalloproteinases and their inhibitors in the regulation of vascular
      morphogenesis, tumor invasion, and metastasis. We report here that mouse sarcoma
      180 cells produce two collagenase inhibitors. These inhibitors were purified by
      heparin-Sepharose affinity chromatography, gel filtration, and C4 reverse phase
      h.p.l.c. Analytical gel electrophoresis of the purified inhibitors (MS-22 and MS
      31) revealed molecular masses of 22,000 and 31,000 Da under reducing conditions,
      and 20,000 and 30,000 Da under nonreducing conditions, respectively. The NH2
      terminal amino acid sequence of MS-22 was identical to that of tissue inhibitor
      of metalloproteinases type 2 (TIMP-2) produced by human melanoma cells [Stetler
      Stevenson et al., 1989, J. Biol. Chem. 264: 17374-17378) over the first 30 amino
      acids. The NH2-terminal amino acid sequence of MS-31 was identical to that of
      murine TIMP-1 [Gewert et al., 1989, EMBO J 6:651-657]. Statistical analysis of
      the amino acid composition data of these two mouse sarcoma 180-derived
      collagenase inhibitors confirms the identification of MS-22 as TIMP-2 and MS-31
      as TIMP-1.

PMID- 7806597
TI  - Medicine as an agency of social control: Part one.

PMID- 7806598
TI  - Opiate antagonists for the treatment of schizophrenia.
AB  - Numerous studies suggest that opiate antagonists may have antipsychotic
      properties. A review of the literature describing the use of naloxone to treat
      schizophrenic patients has shown mixed results. The three studies on naltrexone
      have found no benefit in controlling auditory hallucinations. We present a
      synopsis of these studies.

PMID- 7806599
TI  - Therapeutic progress. III: Diabetic nephropathy.
AB  - Diabetic nephropathy is a common cause of end stage renal failure. Patients
      ultimately require dialysis or transplantation and endure a poor quality of life
      in association with increased mortality. Due to the quantitative significance of
      this problem there is also a considerable financial burden. It has been generally
      accepted that once nephropathy is established it is irreversible although
      aggressive anti-hypertensive treatment can delay its progression. More recently
      there have been numerous reports proposing a specific renal protective role of
      certain drugs. In this article we review the current literature on the use of
      angiotensin converting enzyme inhibitors in diabetic nephropathy. There is strong
      evidence that the use of ACE inhibitors in diabetic nephropathy (in the presence
      or absence of hypertension) slows the progression of deterioration in renal
      function and may even arrest its progression if detected at the microproteinuric
      stage.

PMID- 7806601
TI  - The compatibility of the retail setting with a patient-based practice model:
      reports from community pharmacists.
AB  - The patient counselling and prospective drug utilization review mandates of the
      Omnibus Budget Reconciliation Act of 1990 raise the question of how compatible
      the retail pharmacy setting in the United States is with a patient-based model of
      pharmacy practice. In order to investigate this question, a self-administered
      questionnaire was distributed by pharmacy students to a convenience sample of
      pharmacists with at least one year's experience in the community setting. The
      questionnaire asks respondents to recall two incidents: one that caused them to
      gain or retain a patient or that was for some reason a source of professional
      satisfaction, and one that may have caused the loss of a patient or that they
      would handle differently if faced with the situation or problem again. The
      respondents practice in pharmacies in and around a large midwestern city. Data
      analysis showed that respondents tend to identify patient-based activities when
      recalling appropriate behaviours and traditional or customer-based activities
      when recalling inappropriate behaviours or mistakes. Patient-based activities can
      sometimes result in the loss of business, but they can also result in patronage
      gains, especially when performed in conjunction with good customer service. In
      summary, these pharmacists do implement a patient-based model in some situations.
      The patient-based and customer-based models can be complementary in that the
      patient can benefit from the services of an expert health professional while
      simultaneously being treated with the respect and 'customer knows best' attitudes
      indicative of the retail setting.

PMID- 7806600
TI  - A pharmacokinetic study on two sustained-release formulations of indomethacin in
      normal subjects following a single dose administration.
AB  - A single dose pharmacokinetic study was conducted on two sustained-release
      formulations (75 mg) of indomethacin (Indocid capsules 'A' and Indogesic tablets
      'B'). The study was carried out on 22 healthy male volunteers, who received a
      single oral dose (75 mg) of each product according to a randomized crossover
      design. Blood samples were obtained over a 24 h period, and drug concentrations
      were determined by an HPLC assay. The two products were not found to be
      statistically different with respect to the lag time between dosing and first
      appearance of the drug in the serum (1.0 +/- 0.1 and 0.9 +/- 0.1 h for A and B,
      respectively), or in the time needed to attain the peak concentrations (3.3 +/-
      0.3 and 3.3 +/- 0.5 h for A and B, respectively). The two products, however,
      varied significantly in the peak serum concentrations (2721 +/- 220 and 1797 +/-
      129 ng/ml for A and B, respectively). In terms of the extent of absorption,
      assessed by estimating the area under the concentration-time curve over 24 h, the
      two products were not found to be significantly different (11,575 +/- 630 and
      10,212 +/- 556 ng . h/ml for A and B, respectively). Based on these findings, the
      two formulations can be considered bioequivalent in the extent but not in the
      rate of drug absorption.

PMID- 7806602
TI  - Stability of amoxycillin and potassium clavulanate in co-amoxiclav oral
      suspension.
AB  - A study was carried out using high performance liquid chromatography (HPLC) to
      determine the chemical stability of amoxycillin and potassium clavulanate in
      250/62 co-amoxyclav oral suspension (Augmentin), stored at room temperature (RT,
      20 degrees C) and 8 degrees C over a period of 11 days. The suspension was judged
      to be acceptable if its components maintained at least 90% of their label
      concentrations. During the test period, the amoxycillin component was found to be
      more stable than the clavulanate. Amoxycillin was stable for 7 days at both
      temperatures. Potassium clavulanate maintained at least 90% of its initial
      concentration for 7 days at 8 degrees C but showed more than 40% degradation in
      the same time period at RT. For potassium clavulate the shelf-life, or time taken
      for the original concentration to drop to 90% of its value (t90) at RT was found
      to be 2 days.

PMID- 7806603
TI  - Stability of cefmetazole-doxycycline mixtures in sodium chloride and dextrose
      injections.
AB  - This study involved the mixing of cefmetazole 1 and 2 Gm with doxycycline 100 and
      200 mg, in sodium chloride and dextrose injections. The mixtures were stored
      either at ambient temperature for 96 h or at 4 degrees C for 168 h followed by 8
      h at ambient temperature. HPLC assay of both cefmetazole and doxycycline levels
      were performed at prescribed sampling times. Cefmetazole 1 Gm in doxycycline 100
      and 200 mg mixtures, in sodium chloride injection was not stable up to 4 h, but
      cefmetazole 2 Gm in doxycycline 100 and 200 mg mixtures, in sodium chloride
      injection was stable for up to 24 h. The cefmetazole controls were stable for 72
      h in sodium chloride injection. Cefmetazole 1 Gm with doxycycline 100 mg, in
      dextrose injection was stable up to 72 h. The 2 Gm cefmetazole and 100 mg
      doxycycline mixture in dextrose injection was stable for 96 h. Cefmetazole 1 Gm
      and doxycycline 200 mg in dextrose injection was stable up to 96 h, but the 2 Gm
      cefmetazole-200 mg doxycycline mixture was only stable for 72 h. Cefmetazole
      controls in dextrose injection were stable for 24 h. Doxycycline 100 and 200 mg
      were stable with cefmetazole 1 and 2 Gm, in both sodium chloride and dextrose
      injections for 96 h at ambient temperature. Doxycycline control solutions were
      also stable for 96 h. Cefmetazole 1 and 2 Gm and doxycycline 100 and 200 mg were
      generally stable in both sodium chloride and dextrose injections at 4 degrees C
      for 168 h, and at ambient temperature for 8 h.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7806604
TI  - Preservative efficacy in cefuroxime and ceftazidime eye drop formulations.
AB  - The efficacy of various common antimicrobial preservatives was tested in eye drop
      formulations containing the cephalosporin antibiotics cefuroxime and ceftazidime.
      The British Pharmacopoeia test for the efficacy of antimicrobial preservatives
      was used and the formulations were challenged with Staphylococcus aureus,
      Pseudomonas aeruginosa and Candida albicans. The survival of organisms was
      monitored over 14 days. Cefuroxime sodium, 50 mg/ml, was studied in simple
      aqueous solution, and dissolved in an artificial tear formulation, Sno Tears
      (Smith and Nephew Pharmaceuticals), which contains benzalkonium chloride 0.004%
      w/v. Ceftazidime (50 mg/ml) was also studied in these two vehicles and, in
      addition, in a phenylmercuric acetate solution (0.002% w/v) and chlorhexidine
      acetate (0.02% w/v). Cefuroxime and ceftazidime contributed little, in the short
      term, towards a microbicidal preservative effect in the unpreserved aqueous
      formulations, even against organisms for which they were active. Cefuroxime was
      adequately preserved in a vehicle of Sno Tears, which contains benzalkonium
      chloride as the antimicrobial preservative. Ceftazidime was less well preserved
      in this vehicle, but it was superior to phenylmercuric acetate (0.002% w/v) or
      chlorhexidine acetate (0.02% w/v).

PMID- 7806605
TI  - Bullying at school: basic facts and effects of a school based intervention
      program.

PMID- 7806606
TI  - Cognitive therapy with children and adolescents: from theory to practice.
AB  - Cognitive therapies are now well established as a component for the treatment of
      a wide range of child behaviour problems. There is a great deal of evidence to
      suggest that deficits and distortions in cognitive processes play a role in
      disorders of affect and behaviour in children and adults alike. This has led to
      the development of many different cognitive therapy approaches which aim to
      influence cognitive products, structures and operations. Cognitive assessment
      methods continue to lag behind the developments in therapy, and there is a marked
      need for the development of reliable and valid measures. Empirical studies
      support the value of cognitive interventions, although it is recognised that most
      cognitive therapies include aspects of behavioural techniques, making it
      difficult to draw valid conclusions. Certainly, the results of recent meta
      analytic studies have produced optimistic conclusions and justify the continued
      use of cognitive therapy methods in clinical practice, with a wide range of
      behavioural problems. Cognitive therapy techniques have something to offer with
      internalising and externalising disorders alike. Future research should now focus
      on the identification of methods to enhance the effects of cognitive therapies
      and to determine the characteristics of children who are most likely to benefit
      from these methods. There is some evidence to suggest that younger children may
      benefit less from cognitive therapies than do adolescents. This perhaps reflects
      differences in cognitive and language development. Further consideration needs to
      be given to adapting cognitive therapy methods to the developmental level of
      younger children. Cognitive therapy approaches are now well entrenched within
      many multi-component programmes for most emotional and behavioural disorders in
      children. The degree to which cognitive therapies add to the effectiveness of
      behavioural methods, however, remains to be demonstrated for many types of
      behaviour problem. It is also unclear whether the changes in affect and overt
      behaviour produced in these intervention programmes is actually related to
      improvements in the cognitive activities that were targeted in therapy. From a
      theoretical perspective, however, cognitive therapies have a high degree of face
      validity. If deficits or excesses in specific cognitive events or processes are
      found during assessment, which can be hypothesised to underlie disturbances of
      affect of behaviour, then there is a strong case for attempting to change these
      aspects of cognition.

PMID- 7806607
TI  - Attentional difficulties in hyperactive and conduct-disordered children: a
      processing deficit.
AB  - A random population sample of 1479 Chinese boys from Hong Kong was screened and
      diagnosed in a two-stage epidemiological study. Four groups, age 7-8, were
      distinguished: (1) a pure hyperactive group (HA), (2) a mixed hyperactive/conduct
      disordered group (HA+CD), (3) a pure conduct-disordered group (CD), and (4) a
      normal control group (N). On a visual search task, only the HA children showed a
      specific processing deficit in performance. This confirms the diagnostic value of
      such a deficit for hyperactivity, differentiating it from conduct disorder. The
      failure to find a similar deficit in the HA+CD group raises questions concerning
      the clinical identity of these children. Each group showed a performance
      decrement over time in the visual search task but the decrement did not differ
      between the four groups. This observation is not congruent with the reports of a
      short attention span in hyperactive children; explanations of this apparent
      contradiction are considered.

PMID- 7806608
TI  - When is "impulsiveness" not impulsive? The case of hyperactive children's
      cognitive style.
AB  - On two computerized versions of the Matching Familiar Figures Test (MFFT; Kagan,
      Child Development, 36, 609-628, 1965) pervasively hyperactive and matched control
      children had to identify a target from among five similar foils. One version had
      a temporal structure similar to the manual MFFT and trial length was determined
      by response speed. Hyperactive children behaved in an "impulsive" manner; they
      responded more quickly and made more mistakes than controls. Despite this they
      completed each trial more quickly than controls by identifying the target. On the
      second version, the length of each trial was fixed at 45 seconds. Although both
      groups were equally "reflective", hyperactive children still made more mistakes.
      Implications of these results for research in impulse control in general and
      hyperactivity in particular are discussed.

PMID- 7806610
TI  - First diagnosis of severe mental and physical disability: a study of doctor
      parent communication.
AB  - This study investigates factors associated with satisfaction with medical
      communication at the time of diagnosis of a child's severe mental or physical
      disability. Two competing social psychological models that have been used to
      account for parent patient satisfaction are tested: Korsch's (1968) affective
      model and Ley's (1977) cognitive model. One hundred and sixty six mothers of
      children with severe learning disabilities were questioned about the time when
      their child's disability was first diagnosed. Measures included the child's age
      when diagnosis was made, the length of time parents had been anxious, and how
      satisfied they were with the way they were told the diagnosis. They were asked to
      rate the doctor's affective behaviour and their understanding and memory of the
      information they received. Fifty-eight per cent of parents reported
      dissatisfaction with the communication. Stepwise multiple regression analysis
      showed that Korsch's affective scale was much the strongest predictor, entering
      the equation first, and explaining 35.7% of the variance in satisfaction. Ley's
      cognitive scale entered second, explaining a further 1.4% of the variance.
      Further analysis including the other predictors found that six predictors
      explained 40% of the variance. The implications of the findings for the training
      of medical staff are discussed.

PMID- 7806609
TI  - Children with deficits in attention, motor control and perception (DAMP) almost
      grown up: psychiatric and personality disorders at age 16 years.
AB  - Fifty-six cases with childhood onset deficits in attention, motor control and
      perception (DAMP) were followed-up at age 16 years and compared with 45 children
      without DAMP. Both groups had originally been recruited from the general
      population at the age of 6 years. Psychiatric disorders (affective disorders in
      particular) were more common in the DAMP group. Personality disorders were common
      in both groups, but the DAMP group much more often had a combination of several
      different personality disorders. The reasons for the discrepancies between
      teenagers with and without a prior history of DAMP are discussed.

PMID- 7806611
TI  - Pathways between parental divorce and adult depression.
AB  - A longitudinal study found high levels of depression in women of divorced
      parents, but not in men. In childhood there had been few behavioural differences
      between girls from divorced and intact families. Subsequently, there were
      significant differences in job-changing during early careers, premarital
      pregnancy, and own marital breakdown. Greater adult depression was not
      attributable to social networks, emotional support, recent life events, financial
      circumstances or the main effect of marital status. A significant interaction
      reflected little relationship between parental divorce and symptoms for women in
      first marriages, but a strong relationship in the never married, divorced, and
      remarried.

PMID- 7806612
TI  - Adult outcomes of childhood and adolescent depression. III. Links with suicidal
      behaviours.
AB  - This study followed up into adulthood a group of child psychiatric patients
      suffering from depressive disorders and a closely matched nondepressed child
      psychiatric control group. Depression in childhood was a strong predictor of
      attempted suicide in adulthood. This predictive power was not due to the
      association between childhood depression and other childhood risk factors such as
      conduct disorder or suicidality. Rather, it seemed mostly to reside in the
      association between depression in childhood and major depression in adult life.
      These findings suggest that the pathways from childhood psychopathology to adult
      outcomes can be complex, and depend crucially on what happens later.

PMID- 7806613
TI  - Adolescent onset psychosis. A clinical and outcome study.
AB  - 58 psychotic adolescents between the ages of 12 and 17 diagnosed according to RDC
      criteria were matched with psychiatric comparisons and followed-up using a two
      stage design. Information upon the group as a whole was obtained using death
      records, criminal records and data from the Oxford Record Linkage System. A sub
      sample of 21 matched pairs were interviewed using the Schedule for Affective
      Disorders and Schizophrenia--Life time version (SADS-L) and the Adult Personality
      Functioning Assessment (APFA). The outcome of adolescent schizophrenia was poor
      with 78% continuously ill and socially handicapped. Outcome was better for
      bipolar disorders and schizo-affective disorders and similar to psychiatric
      comparisons.

PMID- 7806614
TI  - [Effect of anti-alpha beta T cell receptor monoclonal antibody on skin allograft
      rejection in mice].
AB  - T cell receptors recognize foreign antigens in the context of glycoproteins
      encoded by the major histocompatibility complex (MHC). alpha beta T cell receptor
      (alpha beta TCR) consists of disulfide-linked heterodimeric glycoproteins
      composed of alpha- and beta-chain. H57-597 is a hamster monoclonal antibody which
      is directed against the beta chain of the murine TCR complex. We purified an anti
      alpha beta TCR monoclonal antibody (anti-V beta mAb) which had very similar
      properties to H57-597, and examined the effect of this mAb in complete H-2
      disparate skin allograft. C57BL/6 (B6) mice grafted with DBA abdominal skin were
      injected intraperitoneally with 250 micrograms of anti-V beta mAb just after
      grafting. These B6 mice rejected their skin grafts with a mean survival time
      (MST: 8.5 +/- 0.8 days) similar to that of the control mice (MST: 8.5 +/- 0.5
      days). To examine the modulation of TCR and the T cell function, B6 mice were
      injected with only one dose of 250 micrograms of anti-V beta mAb, and lymphocytes
      from peripheral blood (PBL), lymph nodes and spleen were tested by flow
      cytometric analysis (FCM), mixed lymphocyte reaction (MLR) and cell mediated
      lympholysis (CML) on days 3, 7, 14, 28, 42, and 56 post-injection. There were no
      detectable Thy-1.2+ alpha beta TCR+ cells present in these organs by FCM for the
      first 1 week after the administration of mAb, but about 26% of Thy-1.2+ cells
      still remained.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7806615
TI  - [Detection and characterization with short TI inversion recovery MR imaging].
AB  - Short TI inversion recovery magnetic resonance imaging (STIR-MRI) with spin echo
      (SE) T1-and T2-weighted images of the pelvis was investigated to evaluate its
      usefulness in detecting and characterizing endometriosis. Thirty-one women
      suspected of having the disease were studied in detail. MR findings with and
      without STIR-MRI were correlated with the results of laparotomy (27 women) and
      laparoscopy (4 women). Surgery revealed endometriosis in 29 women (17 ovarian
      chocolate cysts, 22 intestinal adhesions, 14 cul-de-sac obliterations and 12
      adenomyosis). The other two women did not have endometriosis (uterine prolapse in
      one and submucosal leiomyoma in one). An ovarian chocolate cyst was diagnosed
      when a T1-elongated lesion showed shading, loculus or a low intensity rim on SE
      MR images, and a low intensity rim on STIR-MRI. Only 12 of the 17 chocolate cysts
      and neither of the two hemorrhagic corpus lutein cysts were correctly diagnosed
      on SE MR images, whereas 18 of these 19 cysts were correctly diagnosed because of
      the low intensity rim on STIR-MRI. In the pathological analysis, the rim was
      found to be a fibrous capsule and there were many macrophages which phagocytized
      hemosiderin. For the assessment of ovarian chocolate cysts, accuracy improved
      from 63.2% to 94.7%. As for the adhesion between the intestine and the uterus,
      specificity improved from 61.9% to 90.5% and accuracy improved from 67.7% to
      93.5% when STIR-MRI was used. For the assessment of the cul-de-sac obliteration,
      accuracy improved from 67.7% to 83.8%, although chi 2 analysis showed no
      significance. The major factors for the improved accuracy with STIR-MRI are the
      decrease of the motion artifact owing to the suppression of the fat signal,
      decreased chemical shift artifact and accurate differentiation of fat from
      hemorrhagic component. Therefore, STIR-MRI is a useful and reliable procedure and
      should be used together with SE T1-, T2-weighted images for the assessment of
      endometriosis.

PMID- 7806616
TI  - [Use of patch-scratch tests to determine penicillin and cephem allergies].
AB  - The drug eruptions caused by penicillins and cephems and the patch-scratch test
      reactions to these drugs are discussed herein. Five hundred eighty two patients
      were diagnosed with drug eruption as a result of patch-scratch tests, history,
      gurgle tests or challenge tests in the 22 years from 1971 to 1992 in our
      department. Of these cases 53.8% were caused by penicillins, and 29.9% by
      cephems. The number of cases of allergic reactions to both, especially cephems
      has been increasing steadily over the last 10 years. Patch-scratch tests were
      performed on 382 patients among 385 patients with drug eruption caused by
      penicillin or cephem out of the 582 patients above mentioned. Among these
      patients, the patch-scratch test positive rate for penicillins and cephems was
      84%, suggesting that the patch-scratch test is useful for identifying penicillin
      and cephem allergies. Patch-scratch tests for our antibiotics series were
      performed on 1256 patients with drug eruption or contact dermatitis caused by
      some allergens, whether the allergens were penicillins or cephems, or neither,
      29.5% of these showed positive reactions to penicillins and 12.7% to cephems.
      Among these patients, patch-scratch tests for our penicillin and cephem series
      were also performed on 81 patients, 88.9% of whom showed positive reactions to
      penicillins and 59.3% to cephems. The highest incidence of positive reactions,
      77.8%, occurred with wide spectrum semisynthetic penicillins. Of this group,
      ampicillin had the highest incidence at 58%. In 32 cases, the allergen could be
      detected. As to the clinical types of these cases, maculopapular eruptions and
      erythroderma showed the highest incidence. Cross reactions also occurred within
      the same group, most being for wide spectrum semisynthetic penicillin. The
      optimum concentration of each allergen used in the patch-scratch tests was
      evaluated on the basis of the relationship between the concentration of the
      allergens and the results of the patch-scratch tests. The results were 20w/w% in
      ABPC, AMPC, SBPC, CER, CMZ, CZX and LMOX, 10 w/w% in PCG and CBPC, 5w/w% in CMD.
      Drug lymphocytic stimulation tests were performed in 12 cases, with 15 drugs
      producing positive patch-scratch test reactions. Only 3 drugs showed positive
      reactions, suggesting that this test is unreliable.

PMID- 7806617
TI  - [A study on the fine mucosal pattern in the duodenal bulb].
AB  - To estimate the smallest unit of mucosa in the duodenal bulb radiologically,
      double contrast radiographs were investigated in correlation with endoscopy and
      histological examinations of biopsy specimens. Fine mucosal structures in the
      duodenal bulb were observed in 692 out of 1463 cases (47.4%) in double contrast
      radiographs in our upper gastrointestinal series from January, 1989 to December,
      1990. Fine mucosal structures were subdivided into 3 categories: A; reticular
      and/or granular pattern (60.1%, 416/692), B; diffuse nodular pattern with or
      without additional A pattern (35.3%, 244/692), and C; diffuse tiny barium dots
      (4.6%, 32/692). Three pattern groups were reviewed by endoscopic and histological
      assessment of biopsy specimens in comparison with the control group of
      nonvisualized mucosal pattern (30 cases). Endoscopic observation was carried out
      in 170 out of 692 radiology cases in respect to irregularities in the duodenal
      mucosa (villous pattern, mucosal colour, nodule or depression, or disease) and
      associated diseases of the stomach. Fewer diseases (1 ulcer scar and 7 cases of
      the duodenitis, 15.6%) were visualized in the duodenal bulb than the stomach due
      to a prominent acid secretive function, which was confirmed by the Congo-Red
      method in groups A and B. A flat villi pattern was noted with accompanying
      disease in the duodenal bulb in 8 out of 11 cases of in group C (72.7%). By the
      Whitehead classification of duodenitis, 100% of group A, 98.5% of group B and
      100% of group C revealed low grade inflammation (Grade < 2) in histological
      examinations of biopsy specimens (120 cases). The nodule seen in B pattern was
      histologically composed of nonspecific protruded mucosa (38%, 19/50),
      proliferation of lymphoid follicle (36%, 18/50), Brunner's gland hyperplasia
      (24%, 12/50) or heterotopic gastric mucosa (2%, 1/50). Consequently, mucosal
      patterns A, B and part of C might be appropriate as basic mucosal units of the
      normal duodenal bulb in double contrast radiograph.

PMID- 7806618
TI  - [An experimental study on a chemosensitivity test with alginate microcapsule.
      Feasibility of in vivo succinic dehydrogenase inhibition test].
AB  - A new chemosensitivity test was evaluated by the MTT colorimetric asay with human
      tumor cell lines encapsulated in alginate microcapsules with semipermeable
      membranes. The proliferation of KATOIII in the microcapsules rapidly increased on
      the 4th day after the encapsulation. The change expressed on the proliferation
      curve of the encapsulated KATOIII was approximately 2 days behind the
      proliferation of the suspension culture. The encapsulated cell number reversed
      and further proliferation was recognized after the 12th day. After the incubation
      for 5 hours of encapsulated KATOIII with the medium supplemented with 0.5% MTT, a
      blue formazan crystal formation was observed radiating around the cells in the
      capsules. MTT assay depends on the cellular reduction of the absorbance spectra
      at 540 nm (OD540nm), for complete solubilization of the formazan by DMSO. The
      formazan formation was observed more significantly in serum medium culture than
      in serum free medium. In MIT assay when 0.1 mol succinic acid was added, OD540nm
      of encapsulated KATOIII increased by approximately 50% and its sensitivity also
      increased greatly. In comparison the results of MTT assay for encapsulated
      KATOIII and MKN28 with suspended cells under the same conditions (0.1, 1, 10
      micrograms/ml of MMC and ADR, 0.5, 5, 50 micrograms/ml of 5FU, 10, 30, 50
      micrograms/ml of CDDP), the calculated inhibition index (%) with encapsulated
      cells were similar to the percentages obtained in the former MTT assay. In this
      study with microcapsules, the formazan formation in the capsules and the
      absorbance were macroscopically inhibited when the drug concentration was
      increased. The encapsulated KATOIII, which was implanted intraperitoneally into
      rat with a 16-gauge needle, was recovered at a rate of 70.8% on the 8th day and
      at a rate of 54.5% on the 16th day. The recovered encapsulated KATOIII
      proliferated remarkably forming cell clots on the 8th day after implantation.
      Incubation with MTT promoted formazan formation and sufficient cell viability was
      recognized. The Tegafur concentration in the intraperitoneal microcapsules and
      the microcapsules containing KATOIII after the intravenous administration of
      Tegafur was similar to the intrahepatic level. The 5FU level in the microcapsules
      containing KATOIII was higher than that in the capsules alone. In an attempt to
      conduct an in vivo chemosensitivity test, encapsulated KATOIII and MKN28 were
      intraperitoneally implanted, 4 mg/kg of MMC, ADR and CDDP, and 75mg/kg of 5FU
      were intravenously administered on the 2nd and 4th days after the implantation.
      On the 6th day, MTT assay was performed on the recovered microcapsules containing
      cells and the inhibition index was calculated.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7806619
TI  - [Estimation of localization of the accessory pathway in WPW syndrome with a
      standard 12 lead electrocardiogram. Development of new criteria for children].
AB  - In 128 children with WPW syndrome, localization estimation was based on the
      accessory pathway (ACP) localization criteria of the standard 12 lead
      electrocardiogram for adults proposed by Gallagher et al., Iwa et al., Lindsay et
      al., and Reddy et al. The rate of consistency of each set of criteria with body
      surface mapping (BSM) (based on the criteria of Kamakura et al.) was examined
      along with evaluation of reliability. Among the localization criteria, the most
      reliable set for children was that developed by Iwa et al. The addition of the
      precordial lead QRS transitional zone to the criteria established by Iwa et al.
      was proposed as a means of making the criteria were appropriate for children with
      WPW syndrome. The consistency rate of localization with this new criterion was
      added with the results of BSM reached 93% including interpolations. Thus this new
      localization criterion was considered effective for the estimation of ACP
      localization in children with WPW syndrome.

PMID- 7806620
TI  - [Experimental study of right ventricular assists for severe right ventricular
      failure].
AB  - The efficacy of two right ventricular assist systems for severe right ventricular
      failure caused by multiple ligation of the right coronary artery and right
      ventricular free wall with ventricular septal infarction was studied in 20 adult
      dogs in order to determine a better assist system in terms of hemodynamics and
      ventricular function. Two types of assist systems, a right ventricular bypass
      (RVAS) and an RVAS with intraaortic balloon pumping (IABP) were applied. The
      assist flow changed the preoperative aortic blood flow by 20%, 40%, 60% and 80%,
      respectively. The RVAS decreased the preload of RV and resulted in an effective
      RV assist. But RVAS did not effectively improve the aortic pressure (AP), left
      atrial pressure (LAP), aortic flow (AF), coronary sinus flow (CSF), left
      ventricular end diastolic pressure (LVEDP), LV stroke work (LVSW), or the
      endocardial viability ratio (EVR). On the other hand, RVAS with IABP
      significantly improves AP, LAP, AF, CSF, LVEDP, LVSW, and EVR as compared with
      the data of RVAS only. The optimal assist flow during RVAS with IABP might be 40
      60% of the preoperative aortic blood flow.

PMID- 7806621
TI  - [Effect of tumor necrosis factor and interferon-gamma on platelet-derived growth
      factor (PDGF) A and B gene expression in THP-1 monocytic cells].
AB  - Platelet-derived growth factor (PDGF) is a potent mitogen of mesenchymal cells. A
      and B chains of PDGF are transcribed in atherosclerotic plaques but details of
      the mechanism of the expression of either chains in vivo are not understood. It
      has been suggested that differentiated macrophages, which are the major origin of
      foam cells, but not monocytes hardly secrete PDGF in vitro. In the present study,
      we investigated the effect of 1) tumor necrosis factor-alpha (TNF-alpha), a
      macrophage derived cytokine which promote the differentiation from monocytes to
      macrophages, and 2) interferon-gamma (IFN-gamma), a T cell derived macrophage
      activating factor, on the production and mRNA expression of PDGF A and B chains
      in a human monocytic leukemia cell line THP-1. THP-1 cells were cultured in the
      presence of one of the experimental cytokines with or without the addition of
      phorbol 12-myristate 13-acetate (PMA). PMA is known to induce the differentiation
      of monocytes (including THP-1 cells) to macrophages within a period of 24 hours.
      Thus the treatment of THP-1 cells with a cytokine and/or PMA in vitro was
      expected to mimic the effect of the cytokine during the differentiation of
      monocytes to macrophages in vivo. Unstimulated THP-1 cells expressed no
      detectable amount of PDGF A or B mRNA. The treatment of THP-1 cells with PMA
      resulted in the strong expression of both PDGF A and B mRNAs. Stimulated with TNF
      alpha (50 U/ml) on day 0, THP-1 cells expressed PDGF A mRNA significantly from 1
      up to 3 days after the treatment, whereas the expression of PDGF B and mRNA was
      only weakly detected on day 2. The maximum signal of PDGF A mRNA was ten times
      stronger than that of PDGF B mRNA. Within the same period, relatively small
      number of TNF-alpha treated THP-1 cells had differentiated to macrophages as
      detected by the reduction of nitro blue tetrazolium (NBT) (35% of total cells)
      and by the counting of adherent cells (35% of total cells). THP-1 cells
      simultaneously treated with TNF-alpha and PMA strongly expressed PDGF A and B
      gene. Most remarkably, the expression of PDGF B mRNA was greatly enhanced with
      compared to the treatment with PMA alone. In addition, TNF-alpha augmented the
      secretion of PDGF proteins in PMA stimulated THP-1 cells. In contrast, INF gamma
      per se had no effect on PDGF gene expression, NBT reducing activity and cell
      adherence in unstimulated THP-1 cells.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7806622
TI  - [The new applications of magnetic resonance applicable to the cerebrovascular
      disease].

PMID- 7806623
TI  - [Cerebral blood flow and metabolism in the lesion of white matter by PET and
      SPECT].

PMID- 7806624
TI  - [Oxygen free radicals in cerebral ischemia reperfusion injury].

PMID- 7806625
TI  - [Role of nitric oxide in cerebral ischemic damage].

PMID- 7806626
TI  - [Ischemic tolerance phenomenon and cellular response to brain ischemia].

PMID- 7806627
TI  - [Studies on ischemic tolerance an approach from energy metabolism].

PMID- 7806628
TI  - [A case of syphilitic keratitis and retinopathy].
AB  - This case study focuses on keratopathy and chorioretinopathy resulting congenital
      syphilis. The patient is a 51-year-old man who had diabetes mellitus for eleven
      years. Furthermore he had interstitial keratitis due to syphilis. Both fundi
      showed chorioretinal atrophy. The fundus findings were similar to those of
      retinitis pigmentosa. We examined the visual field, ERG and dark adaptation. The
      serological test for syphilis was positive. A diagnosis of congenital syphilis
      with keratopathy and chorioretinopathy was made.

PMID- 7806629
TI  - [New approach for lipids and its clinical significance. Part II. Remnant like
      particles cholesterol].

PMID- 7806630
TI  - [Neuroimaging in patients with cerebrovascular disease].

PMID- 7806631
TI  - [Endocrine surgery. Series 3. Diagnosis and treatment for primary
      hyperparathyroidism].

PMID- 7806632
TI  - Theory and observation of spontaneous oscillatory contractions in skeletal
      myofibrils.
AB  - At low levels of activation, an isometrically-held myofibrillar preparation on
      the descending limb may exhibit persistent oscillations of period 1-6 s in
      tension and sarcomere lengths. We propose a sarcomeric theory of spontaneous
      oscillatory contraction, based on the phenomena of force creep and delayed length
      activation. The time delay leads to oscillations and controls their period. A
      computer model using these ideas simulates spontaneous oscillatory contraction
      for fixed-end fibres only if isometric tension capacity varies slightly along the
      fibre. The form of this inhomogeneity controls a diversity of spontaneous
      oscillatory contraction behaviour: the tension waveform can vary from large and
      sinusoidal to small-amplitude pulses or chaotic behaviour, and these variations
      are observed in slow-twitch soleus fibres from the same animal (rat). The model
      predicts that oscillatory and quiescent regions coexist in the fibre, with large
      amplitude sawtooth waveforms in sarcomere length in the former as observed. It
      can also generate travelling-wave structures, similar to those found by the Tokyo
      group, in oscillating regions when there is a spatial gradient in isometric
      tension capacity. Phase discontinuities in sarcomere length occur near the
      oscillatory-quiescent boundary. Predictions for the Ca2+ concentrations and
      sarcomere lengths in which spontaneous oscillatory contraction occurs and for
      differences in the spontaneous oscillatory contraction frequencies of fast- and
      slow-twitch fibres compare well with experiment. Spontaneous oscillatory
      contraction is also predicted under isotonic conditions.

PMID- 7806633
TI  - Calcium-activated and stretch-induced force responses in two biochemically
      defined muscle fibre types of the Norway lobster.
AB  - Mechanical properties of thin (< 80 microns) myofibrillar bundles from single
      rehydrated freeze-dried fibres of the superficial abdominal flexor muscle of the
      lobster Nephrops norvegicus have been measured, and subsequently the protein
      content of these fibres has been analysed by SDS-PAGE. Two slow fibre phenotypes
      can be distinguished on the basis of their myofibrillar assemblages and sarcomere
      length (type S1: 6.0-7.5 microns, type S2: 8.0-10.9 microns). Differences (means
      +/- SD, average of seven fibres of each type) were observed in the kinetics for
      Ca2+ activation (half time of force development (ms); S1: 416 +/- 174; S2: 762 +/
      199 plus a delay of 280 +/- 130) and relaxation (half time of force decay (ms);
      S1: 162 +/- 75, S2: 257 +/- 53), for Ca2+ sensitivity of force generation (-log
      [Ca2+] for half maximal activation; S1: 5.40 +/- 0.12; S2: 5.55 +/- 0.08), and of
      the kinetics of stretch activation (delay of the peak of stretch-induced force
      increase (ms); S1: 91 +/- 30; S2: 493 +/- 436). From these results and partly
      also in combination with previously obtained mechanical data on intact fibres it
      can be concluded (1) that S2 fibres are specialized for long-lasting force
      maintenance whereas S1 fibres are adapted for slow movements; (2) intrinsic
      myofibrillar kinetics is not the main time-limiting factor for either activation
      or relaxation of intact fibres under physiological conditions; (3) processes
      which precede crossbridge cycling seem to be the main time-limiting factors for
      the Ca2+ activation of the myofibrils.

PMID- 7806634
TI  - Unloaded shortening of skinned mammalian skeletal muscle fibres: effects of the
      experimental approach and passive force.
AB  - In rabbit, rat and human skinned skeletal muscle fibres the length-time
      relationship of isotonic releases was determined after maximal Ca2+ activation.
      Slack test experiments provided information about unloaded conditions. Force
      clamp experiments of different load were extrapolated for zero load and compared
      with the slack test data. The course length-time relationship for unloaded
      conditions was similar using both approaches. However, slack test data showed a
      triphasic shape which could be fitted by three straight lines (phase I, II, III),
      whereas the data of force clamp experiments exhibited a steady curved shape.
      Consequently, the instantaneous slopes differed in the two relationships, but the
      distance which was shortened during the time interval of phase II was similar in
      both approaches. The ratio between these unloaded shortening velocities resulting
      from force clamp and slack test experiments was 1.01 +/- 0.05 (SD) (n = 25). The
      effects of passive force on the velocity of fibre shortening was investigated in
      skinned rabbit muscle fibres using slack test experiments. A significant increase
      in the unloaded shortening velocity was observed when the sarcomere length of the
      fibres was increased to values which exhibited considerable amounts of passive
      force. The high reproducibility of the isotonic releases required in this study
      was achieved by improving some methodological details. Using these improved
      techniques an identity between the relative fibre and sarcomere shortening was
      observed during the isotonic releases.

PMID- 7806635
TI  - Maximum shortening velocity and coexistence of myosin heavy chain isoforms in
      single skinned fast fibres of rat skeletal muscle.
AB  - Myosin heavy chain composition of a large number (288) of single fibres from slow
      (soleus), and fast (superficial part of tibialis anterior, and plantaris) muscles
      of adult (3-5-month-old) Wistar rats was determined. A combination of SDS-PAGE
      and monoclonal antibodies against myosin heavy chains allowed to identify four
      myosin heavy chain isoforms (1, 2A, 2X, and 2B) and to detect myosin heavy chain
      coexistence. Four groups of fibres containing only one myosin heavy chain (1
      myosin heavy chain, 2A myosin heavy chain, 2X myosin heavy chain, and 2B myosin
      heavy chain), and five groups containing more than one myosin heavy chain (1 and
      2A myosin heavy chains, 2A and 2X myosin heavy chains, 2X and minor amounts of 2B
      (2X-2B fibres), 2B and minor amounts of 2X (2B-2X fibres), and 2A, 2X, and 2B
      myosin heavy chain were identified and their relative percentages were assessed.
      Coexistence of fast myosin heavy chain isoforms was found to be very frequent
      (50% of the fibres in plantaris, and 30% in tibialis anterior), whereas
      coexistence of slow and fast (2A) myosin heavy chain was very rare. Maximum
      shortening velocity (V0) was determined using the slack-test procedure in a
      subset of 109 fast fibres from the above population. The values of V0 formed a
      continuum extending from 2A to 2X to 2X-2B to 2B-2X to 2B fibres. 2A fibres had
      the lowest value of V0 and 2B fibres the highest. Only the differences between 2A
      and 2B and 2A and 2B-2X fibres were statistically significant.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7806637
TI  - Creatine kinase activity associated with the contractile proteins of the guinea
      pig carotid artery.
AB  - Activity and role of creatine kinase associated with contractile proteins of
      vascular smooth muscle have been investigated using skinned guinea-pig carotid
      artery rings. Membrane solubilization was performed with the detergent Triton X
      100. Creatine kinase activity, isoenzyme profile as well as mechanics were
      performed on the Triton skinned carotid artery rings. Total creatine kinase
      activity was 47.3 +/- 9.3 IU g-1 ww and electrophoresis showed BB, MB, and MM
      isoforms (BB-CK being the predominant isoenzyme). One hour incubation with Triton
      X-100, produced predominantly BB-CK remaining with the myofibrils with some MB,
      representing 23% of the preskinned creatine kinase activity. When relaxed carotid
      artery rings were exposed to pCa 9 in the presence of 250 microM ADP, 0 ATP, and
      12 mM phosphocreatine, tension was not significantly different from resting
      tension, but changing to pCa 4.5 caused the carotid artery rings to generate 49.5
      +/- 4.5% of maximal tension. When a high-tension rigor state was achieved (250
      microM ADP, 0 ATP, 0 phosphocreatine, and pCa 9), the addition of 12 mM
      phosphocreatine effected significant relaxation. These observations implicate an
      endogenous form of creatine kinase, associated with the myofilaments, which is
      capable of producing enough ATP for submaximal tension generation and significant
      relaxation from rigor conditions. These results suggest co-localization of
      ATPase, MLCK, and creatine kinase on the contractile proteins of the carotid
      artery. Such an enzymic association may play a role in the energetic supply to
      the contractile apparatus of vascular smooth muscle.

PMID- 7806636
TI  - The effect of K+ on the recovery of the twitch and tetanic force following
      fatigue in the sartorius muscle of the frog, Rana pipiens.
AB  - The goal of this study was to investigate how an increase in the extracellular K+
      (K0+) concentration immediately after fatigue affects the recovery of the resting
      potential, the twitch and tetanic contraction of frog sartorius muscle to further
      understand the role of K+ in the mechanism of fatigue. Resting potentials were
      measured with conventional microelectrodes. Twitch and tetanic contractions were
      elicited by field stimulation. All muscles were fatigued with tetanic
      contractions at a rate of one contraction per second for 3 min while being
      exposed to 3 mmole l-1 K0+. During fatigue development the resting potential
      decreased by 16 mV (control group and pH0 7.2, extracellular pH), while the
      decrease in the twitch force was 32.8%, compared to 79.3% for the tetanic force,
      and 84.6% for the maximum rate of force development of the tetanus. Fatigued
      muscles were also unable to maintain a plateau phase during a tetanus: force
      declined by 14.8% during this phase. During the recovery period under control
      conditions (3 mmole l-1 K0+), all four parameters returned to their pre-fatigue
      values, the recovery of the plateau phase was the fastest (10 min), while that of
      the twitch force was the slowest (80 min). When K0+ was increased to 7.5 or 9.5
      mmole l-1 immediately after fatigue, the recovery rate of the tetanic force and
      plateau phase was reduced. The maximum rate of force development of the tetanus,
      however, recovered at a faster rate than control muscles. The recovery of the
      twitch force was also increased above that of control when K0+ was increased to
      9.0 mmole l-1 (a concentration which maximally potentiates the twitch force of
      unfatigued muscle). Frog sartorius muscles were also tested at pH0 6.4, a pH0
      which inhibits force recovery. At that pH0 the effects of K0+ were similar to
      those observed at pH0 7.2. It is concluded that the role of K+ in muscle fatigue
      is more complex and may not involve just a contribution to the decrease in force
      during fatigue development, but may also contribute to an increase in force
      development under some conditions.

PMID- 7806638
TI  - Phosphorylation of caldesmon by smooth-muscle casein kinase II.
AB  - A caldesmon kinase activity was partially purified from an extract of chicken
      gizzard smooth muscle by sequential chromatography on columns of DEAE-Sephacel,
      MonoQ and Superose 12. This kinase was identified as casein kinase II by Western
      blotting using peptide-directed antibodies raised against the alpha, alpha' and
      beta subunits of human casein kinase II; the smooth muscle enzyme consisted of
      similar subunits of M(r) 43,000 (alpha), 39,000 (alpha'), and 27,000 (beta).
      Phosphorylation of caldesmon and casein by smooth muscle casein kinase II was
      optimal at approximately 0.1 M NaCl, did not require second messengers, and was
      inhibited by heparin. The kinase utilized either GTP or ATP as a substrate.
      Caldesmon was phosphorylated to approximately 1 mol Pi mol-1 caldesmon by smooth
      muscle casein kinase II with a Km for caldesmon of 4.9 microM. Two-dimensional
      thin-layer electrophoresis indicated phosphate incorporation into both serine and
      threonine. All the incorporated phosphate was recovered in the N-terminal peptide
      (residues 1-152) generated by cleavage at cysteine 153 with 2-nitro-5
      thiocyanobenzoic acid. Purification of tryptic phosphopeptides and N-terminal
      sequencing revealed two principal sites of phosphorylation: serine 73 and
      threonine 83. The following four synthetic peptides corresponding to this domain
      of caldesmon were examined as substrates of casein kinase II: A =
      RRREVNAQNSVAEEE; B = AQNSVAEEE; C = RSTDDEAA; D = SVAEEETKRSTDDE. Interestingly,
      only peptides C and D were phosphorylated and both only at threonine.
      Phosphorylation of intact caldesmon did not affect the pattern of chymotryptic
      digestion suggesting that it does not induce a significant conformational change
      in the protein substrate. Phosphorylation also had no effect on the binding of
      caldesmon to actin or on the caldesmon-mediated inhibition of actomyosin MgATPase
      activity. However, phosphorylation completely abolished the interaction of
      caldesmon with immobilized smooth muscle myosin. These results are consistent
      with the localization of the myosin-binding domain near the N-terminus of
      caldesmon and of the actin-binding domain near the opposite end of the elongated
      molecule. Casein kinase II may therefore play a role in regulating caldesmon
      myosin interaction and the ability of caldesmon to cross-link actin and myosin
      filaments in smooth muscle.

PMID- 7806639
TI  - Comparison of the effects of 2,3-butanedione monoxime on force production, myosin
      light chain phosphorylation and chemical energy usage in intact and permeabilized
      smooth and skeletal muscles.
AB  - The primary goal of this study was to determine the utility of 2,3-butanedione
      monoxime as a tool for determining and separating the chemical energy usage
      associated with force production from that of force-independent, or 'activation'
      processes in smooth and skeletal muscles. We determined the effects of 2,3
      butanedione monoxime on force production, myosin light chain phosphorylation and
      high energy phosphate usage in intact and permeabilized smooth (rabbit taenia
      coli) and skeletal (mouse extensor digitorum longus) muscles. In the intact
      taenia coli, 2,3-butanedione monoxime depressed the tonic phase of the tetanus,
      contractures evoked by high potassium (90 mM) and by carbachol (10(-5) M) and the
      small force response evoked by these agonists after treatment with D-600 (10(-5)
      M). In the electrically stimulated intact taenia coli 2,3-butanedione monoxime (0
      20 mM) caused a proportional inhibition of tetanic force output, myosin light
      chain phosphorylation and high energy phosphate usage (ED50 approximately 7 mM
      for all these parameters). At 20 mM 2,3-butanedione monoxime, force and energy
      usage fell to near zero and the degree of myosin light chain phosphorylation
      decreased to resting values, indicating a shut-down of both force-dependent and
      force-independent energy usage at high concentrations of 2,3-butanedione
      monoxime. In permeabilized taenia coli, 2,3-butanedione monoxime had little or no
      depressant effects on force production, ATPase activity or calcium sensitivity.
      2,3-butanedione monoxime had a very modest inhibitory effect on the in vitro
      motility of unregulated actin filaments interacting with thiophosphorylated
      myosin. In solution, 2,3-butanedione monoxime inhibited myosin light chain
      kinase, but not the phosphatase (SMP-IV). These results suggest that the major
      effect of 2,3-butanedione monoxime is not on the contractile proteins themselves,
      but rather on calcium delivery during excitation, thereby reducing the degree of
      activation of myosin light chain kinase and subsequent activation of myosin by
      light chain phosphorylation. Thus, 2,3-butanedione monoxime is not useful for the
      determination of the energetics of activation processes in smooth muscle because
      of its inhibition of both force-dependent and force-independent processes. In
      contrast, in the intact mouse extensor digitorum longus, 2,3-butanedione monoxime
      inhibits tetanic force production (ED50 approximately 2 mM) to a much greater
      extent than myosin light chain phosphorylation. When 2,3-butanedione monoxime was
      used to manipulate force production in muscles at L(o), it was found that
      approximately 60% of the total energy usage was force-independent and the
      remainder was force-dependent.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7806640
TI  - Comparison of the foetal development of fibre types in four bovine muscles.
AB  - The pattern of expression of different types of myosin heavy chains and the
      development of different generations of muscle cells during foetal life were
      studied in four bovine muscles with widely varying characteristics, the Masseter,
      Longissimus thoracis, Cutaneus trunci and Diaphragma. Different complementary
      techniques were performed: immunocytochemistry, electrophoresis, immunoblotting
      and ELISA. Monoclonal antibodies against different myosin heavy chain isoforms
      were used. The results confirmed the existence of at least two generations of
      cells during foetal development in cattle. A first generation, which appeared at
      a very early stage, gave rise to adult type I fibres. A second generation, made
      up of different cell populations, gave rise to adult fast type IIA and IIB
      fibres, and to type IIC. In the slow muscles, it also seemed to give rise to type
      I fibres. The beginning of myogenesis was characterized in the different cell
      generations by the expression of transitory myosin forms that are not found in
      the adult. Type 1 myosin heavy chain was observed from 90 days whereas the fast
      types, 2a and 2b, were present from 210 to 230 days, at which stage the foetal
      form disappeared. Muscles that have greatly different contractile characteristics
      in the adult exhibit also different profiles of differentiation: the Diaphragma
      was the first to develop, followed by Cutaneus trunci, Longissimus thoracis and
      Masseter.

PMID- 7806641
TI  - Studies on the mechanism of force production in intact striated muscles.

PMID- 7806642
TI  - A comparison of combat's effects on PTSD scores in veterans with high and low
      moral development.
AB  - This study was designed to explore the effects of moral development on the
      relationship between combat intensity and severity of posttraumatic stress
      disorder. The effect of combat intensity on PTSD Interview total scores and
      several individual stress disorder symptom ratings was substantial in a Low Moral
      Development sample, but negligible in a High Moral Development group. These data
      suggest that moral development may blunt the effect of combat severity on PTSD.
      These effects were strongest on items that describe reexperiencing of the trauma
      and exaggerated arousal. Possible interpretations of the results and several
      caveats were discussed.

PMID- 7806643
TI  - Gender-related subcomponent differences in high type A subjects.
AB  - Thirty Type A males and 30 Type A females were administered an expanded version
      of the Structured Interview designed to assess 11 Type A subcomponents. The
      purpose was to determine whether males and females follow different subcomponent
      routes in achieving their Type A status. As predicted, males scored higher than
      females on two of four anger-related variables. Contrary to prediction, males
      scored higher than females on the subcomponent of exaggerated social control.
      These findings were interpreted as providing some support for the notion of
      differing gender-related subcomponent routes for achieving Type A status. These
      findings also may have implications for the higher incidence of coronary heart
      disease in high TABP males vs. females.

PMID- 7806644
TI  - Long-term effects of trauma: post-traumatic stress among civilian internees of
      the Japanese during World War II.
AB  - This study examined predictors and health-related effects of post-traumatic
      stress among 129 civilian internees of the Japanese during World War II. Post
      traumatic stress disorder was noted in 36.7% within the 6 months after their
      release and in 15.0% within the most recent 6 months. Women were more likely than
      men to indicate post-traumatic stress disorder within the 6 months after their
      release. Higher incomes were associated with lower levels of post-traumatic
      stress within the most recent 6 months. After controlling for demographic and
      internment-related factors, higher levels of post-traumatic stress were
      associated with poorer physical health. This association was stronger among older
      internees than among their younger counterparts. Implications of the findings for
      clinical gerontology are discussed.

PMID- 7806645
TI  - Relationship of NEO-PI to personality styles and severity of trauma in chronic
      PTSD victims.
AB  - The relationship of the NEO-PI to personality disorders was evaluated in a
      clinical population. Eighty subjects with post-traumatic stress disorder (PTSD)
      were given this measure, along with the MCMI-II and PTSD and combat scales. Two
      questions were addressed: (1) What is the relationship of NEO-PI domains and
      facets to personality disorders?; and (2) What is this scale's relationship to
      PTSD problems? Results support previous studies that employed a clinical
      population, but with lower correlation coefficients. For the most part, then, the
      NEO-PI domains and facets correlated in expected ways with the MCMI-II. On PTSD
      measures, N accounted for the majority of the variance, but other domains were
      entered when independent regression equations were calculated to account for
      different personality disorders.

PMID- 7806646
TI  - Sustaining fantasies and psychopathology in a normal sample.
AB  - This study tested the hypothesis that the types of sustaining fantasy (fantasy
      used as a source of comfort at times of high stress) previously found to be
      associated with inpatient status also would be related to indications of
      psychopathology in a college sample (N = 124). The Sustaining Fantasy
      Questionnaire (SFQ; Zelin et al., 1983) provided a measure of fantasies of
      power/revenge, death/illness, withdrawal/protection, suffering, love/closeness,
      and restitution. The F scale of the MMPI and the number of MMPI clinical scales
      at or above 70 were used as the measures of general pathology. Results indicated
      that four of the hypothesized six types of fantasy-power/revenge, death/illness,
      withdrawal/protection, and suffering-related to psychopathology. No specific
      configuration of scores on the MMPI clinical scales was noted for any of these
      four types of fantasy.

PMID- 7806647
TI  - The role of stressful life events in duodenal ulcer recurrence: a prospective
      study.
AB  - This study prospectively assessed whether stressful life events (LE) were
      predictive of duodenal ulcer (DU) recurrence during remission of disease. We
      administered Paykel's Interview for Recent Life Events to 80 patients to assess
      events that occurred 12 months prior to the first interview and again 6 to 12
      months later for LE that occurred during the interval. Upper gastrointestinal
      endoscopy detected DU recurrence in 11 patients. Prospective data analysis showed
      no significant difference in LE between relapsing and relapse-free groups,
      whereas retrospective analysis showed significantly more LE (p > .03) among
      relapsing patients. LE seems to have played a marginal role in DU recurrence.

PMID- 7806648
TI  - The stability and prediction of depressive mood states in college students.
AB  - Objective criteria for predicting dysphoric mood states in college students from
      measures of stress and cognitive and personality variables were developed and
      cross-validated. Contrary to Beck's diathesis-stress model of depression,
      although dysfunctional attitudes, together with the number and impact of life
      events, self-esteem problems, and level of traditional feminine personality
      characteristics, predicted concurrent levels of depressive symptoms, initial
      level of depression was the best predictor of future depression. Cross-validation
      of the criteria resulted in accuracy rates of 86 to 87%. Implications of these
      results and some secondary findings were discussed.

PMID- 7806649
TI  - Using the brief symptom inventory to profile monolingual Spanish-speaking
      psychiatric outpatients.
AB  - As part of a larger study (Acosta, Evans, Hurwicz, & Yamamoto, 1987), a
      translated version of the Brief Symptom Inventory (BSI) was given to 153
      monolingual Spanish-speaking psychiatric outpatients in the Los Angeles area. The
      raw mean scores on the nine primary symptom dimensions and the Global Severity
      Index (GSI) of the Spanish-speaking population were compared with the published
      raw mean scores of a normative sample of English-speaking psychiatric
      outpatients. Results suggested that the Spanish-speaking population had higher
      symptom levels on several dimensions and the GSI. It was suggested that the BSI
      could be a potentially useful instrument for self-reported psychiatric
      symptomatology among the Spanish-speaking population if an appropriate
      translation of the BSI were used.

PMID- 7806651
TI  - The influence of acculturation and racial identity attitudes on Mexican
      Americans' MMPI-2 performance.
AB  - Examination of the relationships among acculturation, racial identity, and the
      newly revised MMPI is warranted. This study investigated the degree to which
      racial identity influences Mexican-Americans' performance on the L, K, and MF
      scales of the MMPI-2. Also investigated were individual differences in
      performance on the L, K, and MF scales as a function of acculturation. Fifty-one
      Mexican-American undergraduates from Washington State University participated by
      completing an acculturation scale, a racial identity attitude scale, and the MMPI
      2. Results indicated that performance on the L and K scales is influenced by
      racial identity attitudes and levels of acculturation, however, no evidence was
      found to suggest a relationship between cultural variables and performance on the
      MF scale.

PMID- 7806650
TI  - Coping and MCMI-II symptom scales.
AB  - The associations of the MCMI-II symptom scales with dispositional coping
      strategies were studied among 239 psychiatric outpatients. A similar core-pattern
      of emotion-focused coping was associated with all symptom scales except the
      bipolar scale. High scores on the MCMI-II symptom scales were associated with low
      use of adaptive emotion-focused coping (e.g., seeking social support) and high
      use of maladaptive emotion-focused coping (e.g., disengagement). Thought
      disorder, drug dependence, and delusional disorder also were associated with
      reduced use of problem-focused coping. The findings support the theoretical
      distinction between adaptive and maladaptive emotion-focused coping. The
      potential negative impacts of this coping pattern in terms of mental health and
      life adaptation are discussed.

PMID- 7806652
TI  - Gender-controlled measures of socially desirable responding.
AB  - Items in various scales that measure socially desirable responding (SDR) appear
      to vary in significance in male and female respondents. Recent findings suggest
      that females are more sensitive to the contents of more than two-thirds of such
      items. As a result, scales that measure SDR cannot be considered gender balanced,
      not to mention gender free. We examined three levels at which SDR items can be
      construed as gender controlled and arrived at a formula for item selection in the
      development of gender-controlled scales. Application of the formula resulted in
      the 10-item Gender-Free Inventory of Desirable Responding (GFIDR), with an inter
      item reliability of .68, and the 12-item Gender Balanced Inventory of Desirable
      Responding (GBIDR), with an inter-item reliability of .71. The distribution
      characteristics of the two scales suggested that gender differences in the higher
      moments should be considered in the interpretation of results based on otherwise
      gender-controlled scales.

PMID- 7806653
TI  - WAIS-R intersubtest scatter in patients with dementia of Alzheimer's type.
AB  - This study explored the relationship between three indices of intersubtest
      scatter and level of cognitive deterioration in a sample of 104 patients with
      dementia of Alzheimer's type, who ranged in age between 52 and 84 years. Scatter
      was highly related to education and premorbid level of functioning. Advancement
      of dementia was shown to be associated with decrease in scatter, which suggests
      caution in interpretation of high magnitude of inter-subtest scatter as an
      indication of brain dysfunction. Easy-to-calculate range of scatter proved to be
      adequate measure of scatter. Calculation of more complex indices, such as PVI,
      provides only minimal incremental gain.

PMID- 7806654
TI  - Involvement and role playing.
AB  - Three studies focused on involvement as a function of type and content of the
      role play, experimenter behaviors, and proportion of time in scenario roles.
      Several measures of involvement were obtained. Generally, there was a low
      correlation between involvement estimated by observers and self-reported
      involvement; subjective involvement also was related more consistently to other
      variables.

PMID- 7806656
TI  - Adjustment issues with adult children of alcoholics.
AB  - The current study assessed locus of control, general level of life satisfaction,
      and self-reported grade-point averages among adults who had experienced either
      alcoholism within the family of origin, traumatic life events other than
      alcoholism, or who indicated neither problem during their childhood. Results
      indicated that both the adult children of alcoholics (ACOA) and traumatic
      experience (TE) groups had lower life satisfaction scores than the control group.
      Significantly lower levels of locus of control also were found for the ACOA group
      in comparison to the control group. There were no significant differences among
      the three groups based on self-reported GPAs. Results of the current study
      support the concept that family dysfunction during childhood can influence
      negatively later life experiences and adjustment.

PMID- 7806655
TI  - Factor analytic structure and stability of the separation-individuation test of
      adolescence.
AB  - The present study was undertaken to examine internal structural properties of the
      Separation-Individuation Test Adolescence (SITA; Levine, Green, & Millon, 1986).
      In 1990, 131 late adolescent undergraduate university students received the SITA;
      2 years later, 79 of these same subjects were reassessed. Principal components
      analyses were conducted for the 1990 and 1992 samples, and internal consistency
      reliabilities (Cronbach's alpha) were calculated for each subscale. The internal
      structural properties converged moderately to strongly for the following scales:
      Practicing Mirroring, Engulfment Anxiety, Dependency Denial, Nurturance Seeking,
      and Teacher Enmeshment. These findings parallel those of Levine (in press). The
      developmental impact of the late adolescent separation-individuation process may
      explain in part some different clusterings of scale items over time.

PMID- 7806657
TI  - Characteristics of families of children who refuse post-divorce visits.
AB  - Compared to 88 non-refusers, 12 children who refused post-divorce visits with
      their noncustodial parents were significantly more likely to be female, to be the
      oldest child at home, to be in special education, and to have at least one parent
      with evidence of psychopathology, particularly substance abuse, violence toward
      spouse, suicidal behavior, or psychosis. Most children in both groups lived
      primarily with their mothers.

PMID- 7806658
TI  - Development of an instrument to assess clinicians' recognition memory using a
      videotaped stimulus interview.
AB  - This study represents the development of an instrument to assess clinicians'
      memory using a videotaped counseling interview. The instrument, called the
      Recognition Checklist (RC), consists of 60 items of information based on the
      content presented by the client on the stimulus tape. Initial findings indicated
      that this instrument has promising reliability and validity and warrants further
      development and application to the study of clinicians' memory of the interview
      process and interviewing skill training.

PMID- 7806659
TI  - Ultrasound evaluation of hepatic and splenic microabscesses in the
      immunocompromised patient: sonographic patterns, differential diagnosis, and
      follow-up.
AB  - High-dose chemotherapy, especially for bone marrow transplantation, causes a
      great degree of immunosuppression, and thus carries the risk for invasive fungal
      infections. Although hepatic and splenic involvement in disseminated candidiasis
      is frequent, involvement of these organs is rarely appreciated antemortem. During
      the last decade, focal hepatosplenic candidiasis has been recognized increasingly
      by ultrasound. We report the sonographic and clinical findings of 6 patients: 3
      AML (acute myeloid leukemia), 2 NHL (non-Hodgkin's lymphoma), and 1 HD (Hodgkin's
      disease) who demonstrated multiple, small-nodule, hypoechoic lesions in spleen
      and/or liver after high-dose chemotherapy. All patients were in complete
      hematologic remission when the study was performed. Septic fever was unresponsive
      to antibiotic therapy. Granulocytopenia (< or = 1000/mm3) was seen for at least
      10 days. However, the manifestation of hepatolienal microabscesses became
      apparent by ultrasound only after the neutrophil count returned to normal in all
      but 1 patient. Microabscesses decreased or disappeared on follow-up examination
      after antifungal treatment. Systemic candida infection was confirmed
      serologically. Sonographic-guided abscess biopsy (n = 3) revealed
      necrosis/abscess. Structural inhomogeneity of parenchymal organs was seen for
      several months after therapy.

PMID- 7806660
TI  - Ultrasound anthropometric reliability.
AB  - Method errors and reliabilities were estimated for seven sonographic measurements
      in pregnancies of 106 women examined between January and July 1989. Teams of two
      experienced sonographers replicated the following measurements: biparietal
      diameter (BPD), occipital-frontal diameter (OFD), anterior-posterior diameter
      (APD), transabdominal distance (TAD), and femur diaphysis length (FDL).
      Multilevel modeling procedures were used to estimate the variance components.
      Significant (p < 0.01) covariates in the fixed part of the model included an
      increase in error with greater parity, estimated menstrual age (EMA), and
      maternal abdominal wall thickness (taken at the umbilicus). Intraobserver
      reliability ranged from 85.2% (AC) to 99.3% (FDL); interobserver reliability
      ranged from 80.8% (TAD) to 92.4% (FDL). Method errors, describing the expected
      error for 68% of the measurements taken, ranged from 0.8 mm to 7.7 mm
      (intraobserver) and from 1.2 mm to 7.8 mm (interobserver). These results suggest
      that large error components should be considered in the interpretation of the
      reliability of ultrasonographically obtained measurements.

PMID- 7806661
TI  - Thyroid nodules: clinical effect of ultrasound-guided fine-needle aspiration
      biopsy.
AB  - Ultrasound (US)-guided fine-needle aspiration biopsy (FNA) was performed on 268
      thyroid nodules (135 palpable, 133 nonpalpable) in 210 patients with various
      thyroid conditions; 62 nodules also had palpation-guided FNA. Surgical pathology
      was obtained in 67 malignant nodules and 32 benign nodules. Although the initial
      failure rate for palpation-guided FNA (12 of 62) was significantly higher than
      that for US-guided FNA (10 of 268) (p < 0.001), sensitivity (96%), specificity
      (91%), accuracy (94%), and positive (96%) and negative predictive values (91%) of
      US-guided FNA for malignancy (n = 99) were not significantly different from those
      (88%, 90%, 88%, 95%, and 75%, respectively) of palpation-guided FNA (n = 34) for
      those nodules where an adequate biopsy was obtained. US-guided FNA established a
      correct diagnosis in 20 of 22 patients with nonpalpable malignancy and in another
      nodule in the opposite thyroid lobe in 16 of 17 patients with thyroid malignancy.
      This procedure determined the correct cancer staging in 19 of 21 patients. US
      guided FNA can reliably (1) select a patient who needs surgery and (2) avoid
      unnecessary surgery. This technique will help determine a cancer staging and
      institute an appropriate treatment.

PMID- 7806662
TI  - Renal blood flow velocity in neonates with and without umbilical artery
      catheters.
AB  - We performed an observational prospective cohort study on the applicability of
      two-dimensional echocardiography with pulsed Doppler technique as a noninvasive
      modality to serially evaluate renal blood velocities in premature neonates with
      and without umbilical artery catheters. We also sought to determine the incidence
      of umbilical artery catheter-related thrombus formation in our neonatal intensive
      care unit. We established normative values for renal artery blood flow velocities
      in premature neonates and postulate that this echo-Doppler technique is valid and
      can be used to evaluate renal developmental physiology in the neonatal
      population. In addition, we observed that even in the absence of clinical
      sequelae due to thrombus formation, the presence of a thrombus in the aorta
      caused abnormalities in renal hemodynamics.

PMID- 7806663
TI  - Image-directed and color Doppler studies of gallbladder tumors.
AB  - Thirteen cases of primary adenocarcinoma of the gallbladder (GB), 1 of malignant
      fibrous histocytoma, 3 of metastatic adenocarcinoma, 5 of adenoma, 5 of polypus,
      2 of xanthogranuloma, 6 of chronic cholecystitis, 4 of acute cholecystitis, and 8
      of subacute cholecystitis were studied by image-directed and color Doppler
      ultrasonography (CDUS). All of the 14 cases of primary GB cancer (10 masses, 4
      thickening wall) were found to have a high velocity arterial blood flow signal in
      the wall of the GB. In contrast, the 3 cases of metastatic cancer of the GB had
      no blood flow signal in the wall of the GB. For the 30 cases of benign lesions of
      the GB, only in 12 cases was a low velocity blood flow signal found. Nine of 10
      cases of primary GB malignancy were found to have high velocity arterial blood
      flow signals in the tumor masses. No blood flow signal was observed in the masses
      of 13 cases (3 of metastatic adenocarcinoma, 5 of adenoma, 5 of polypus). An
      abnormal high velocity arterial blood flow signal observed within masses in the
      GB or in the GB wall is a significant feature of primary GB cancer and thus helps
      to differentiate primary GB cancer from metastatic and benign lesions of the GB.

PMID- 7806664
TI  - Doppler color flow findings in malignant fibrous histiocytoma of the scrotum and
      perineum.

PMID- 7806665
TI  - Prenatal diagnosis of lissencephaly: Miller-Dieker syndrome.

PMID- 7806666
TI  - Evaluation of tibialis anterior tendon rupture by ultrasonography.

PMID- 7806667
TI  - Sonographic detection of Menetrier's disease in children.

PMID- 7806669
TI  - Ectopia cordis in a triploid fetus: first-trimester diagnosis using transvaginal
      color Doppler ultrasonography and chorionic villus sampling.

PMID- 7806668
TI  - Sonographic diagnosis of Fournier's gangrene.

PMID- 7806670
TI  - Gallbladder wall thickening in children with infectious mononucleosis.

PMID- 7806671
TI  - Utility of radiographic crestal lamina dura for predicting periodontitis disease
      activity.
AB  - The relationship between radiographic crestal lamina dura and periodontitis
      disease-activity was studied longitudinally in 51 treated adult patients on a
      systematic 3-month maintenance program. The presence or absence of crestal lamina
      dura at 1809 interproximal sites was scored from periapical and bitewing
      radiographs taken at baseline of a 36-month maintenance care period. Semi-annual
      clinical evaluations by 2 independent examiners were carried out on each patient,
      with disease recurrence defined as sites revealing a > or = 3 mm increase in
      probing depth from baseline, or a > or = 2 mm increase in probing depth together
      with a > or = 2 mm loss of relative attachment level from an occlusal reference
      stent. Over the 36-month study period, 23 (45%) patients exhibited disease
      recurrence at 55 (3%) interproximal tooth sites scored for baseline crestal
      lamina dura. Absence of detectable baseline crestal lamina dura yielded high
      sensitivity (87-100%), but low specificity (17%) and low positive predictive
      values (0.8-3.2%), for localized periodontitis recurrence. In contrast, no sites
      exhibiting an intact baseline crestal lamina dura demonstrated periodontitis
      recurrence up to 24 months from baseline (100% positive predictive values).
      Presence of radiographic crestal lamina dura was positively associated with
      clinical periodontal stability (summary odds ratio for sites = 2.6, P = 0.0004),
      and negatively associated with periodontitis recurrence (summary odds ratio for
      sites = 0.4, P = 0.0004), for the 36-month study period. Evaluation of
      radiographic crestal lamina dura status appears valuable for assessing the risk
      of periodontitis disease-activity at inter-proximal tooth sites in patients on
      maintenance care programs.

PMID- 7806672
TI  - Proximal restorations and periodontal status.
AB  - The purpose of the present investigation was to evaluate the influence of
      overhanging marginal restorations on periodontal status and whether any such
      influence is modified by the patient's oral hygiene level and degree of
      radiographic attachment loss. The investigation was conducted as a retrospective
      study on a consecutive referral population. Periodontal pockets at proximal sites
      with marginal overhangs were significantly deeper (0.42 mm) compared to sites
      with metal restorations without overhangs. This difference was larger (0.62 mm)
      for sites with radiographic attachment loss < or = 6 mm, while no significant
      difference was found for sites with radiographic attachment loss > 6 mm. In
      patients with a mean radiographic attachment loss < or = 5 mm, an overhanging
      restoration margin was associated with a significantly increased loss of
      radiographic attachment (0.66 mm). It was concluded that the influence of a
      marginal overhang on pocket depth and radiographic attachment decreases with
      increasing loss of periodontal attachment in periodontitis-prone patients. The
      effect on pocket depth of a marginal overhang may act synergistically,
      potentiating the effect of poor oral hygiene.

PMID- 7806673
TI  - The prevalence of A. actinomycetemcomitans, P. gingivalis and P. intermedia in
      selected subjects with periodontitis.
AB  - The present study was carried out in a private periodontal practice. 8 clinical
      criteria were chosen to select patients for microbiological examination. These
      criteria characterize prominent features of disease which at the start, during,
      or in the maintenance phase of treatment suggest difficulties in the progress of
      the periodontal therapy. Based on these clinical characteristics, an inventory
      was made of the prevalence of the 3 putative periodontal pathogens:
      Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Prevotella
      intermedia. Out of 320 referred patients 91 patients did meet > or = 1 of the
      clinical criteria and consequently were selected for microbiological examination.
      Results showed that young patients (19-30 years) with periodontitis demonstrated
      the presence of A. actinomycetemcomitans more often (69%: p < 0.005) compared to
      older age cohorts. A. actinomycetemcomitans was found more often when localized
      breakdown (in particular in the 1st molar and incisor region) was observed and in
      patient who responded poorly to scaling and rootplaning. P. gingivalis and P.
      intermedia were most frequently recovered in patients showing primarily a bone
      loss pattern of angular defects of > or = 5 mm. Retrospectively, these patients
      were further categorized, based on full mouth radiographs, in (1) patients with
      primarily horizontal bone loss and (2) patients with primarily angular bony
      defects. Results showed that A. actinomycetemcomitans occurred less frequently in
      patients showing horizontal bone loss (p < 0.05).

PMID- 7806674
TI  - Comparison of different approaches to assess bleeding on probing as indicators of
      gingivitis.
AB  - The purpose of this study was to evaluate different methods of eliciting gingival
      bleeding as indicators of gingival inflammation in the experimental gingivitis
      model. Following a period of stringent oral hygiene, 103 dental students were
      scored for plaque and gingival bleeding assessed by 4 methods. From this group,
      41 volunteers were randomly allocated to 2 treatment groups. Dental students with
      clean teeth and healthy gingivae were asked to abolish all mechanical tooth
      cleaning in the lower jaw for a period of 3-weeks. During the 21-day experimental
      period, chlorhexidine (Peridex) or a placebo mouthrinse was applied to the lower
      jaw. Subjects brushed the upper jaw with a standard toothpaste. In principal, 2
      different methods were employed to provoke bleeding: (1) at the marginal gingival
      tissue by running a probe along the soft tissue wall at the orifice of the
      pocket, and (2) by probing to the "bottom" of the pocket. Variations in the
      methods were based on angulation (AngBI, ParBI) of the probe in relation to the
      tooth surface and to the probing force (PPBI.25N, PPBI.75N). 1 randomly selected
      quadrant in the lower jaw was scored using the AngBI. The opposing quadrant was
      scored with a randomly-allocated bleeding index, either ParBI, PPBI.25N or
      PPBI.75N. The results of this study confirm earlier findings that the angulation
      of the probe determines the number of sites with bleeding observed. It also
      indicates that bleeding as elicited by probing to the bottom of the pocket is a
      poor indicator of early gingivitis. It is recommended that gingivitis should be
      assessed by probing the marginal gingiva.

PMID- 7806675
TI  - Kinetics of spiramycin/metronidazole (Rodogyl) in human gingival crevicular
      fluid, saliva and blood.
AB  - The peripheral distribution of spiramycin and metronidazole, which are combined
      in the proprietary drug "Rodogyl", has been studied in gingival fluid, saliva and
      blood after a single administration to 12 healthy volunteers and after repeated
      administration to 4 patients with recurring severe periodontitis. Analysis of the
      2 antibiotics have been performed at regular intervals during the 24-h period
      immediately following the administration to the volunteers and after the 1st and
      the 15th days of repeated administration to the patients. The results show that
      gingival fluid contains concentrations of spiramycin and metronidazole higher
      than those needed to inhibit the growth of periodontopathic bacteria. Spiramycin
      was found at higher concentrations in GCF than in blood, although this feature
      was not found for metronidazole, which was administered simultaneously and showed
      similar concentrations in both fluid and serum. Such high concentrations persist
      for a long time, and suggest the potential of this compound in the treatment of
      severe cases of periodontitis.

PMID- 7806676
TI  - Neurogenic component in ligature-induced periodontitis in the rat.
AB  - Effect of ligation on the vascular permeability in the gingiva and alveolar
      mucosa encircling the mandibular left 1st molar was studied in rats with and
      without capsaicin pretreatment. Vascular permeability was assessed by the Evans
      blue extravasation. Ligation caused a significant augmentation in vascular
      permeability of the gingivomucosal tissue at day 8 (right: 18.14 +/- 1.68
      micrograms g-1; left (ligature): 38.21 +/- 2.43 micrograms g-1, n = 8, p < 0.001)
      and at day 14 (right: 20.31 +/- 1.71 micrograms g-1: left (ligature): 36.98 +/-
      2.73 micrograms g-1, n = 8, p < 0.001). 4 days after ligation, no difference
      could be observed in vascular permeability in the oral mucosa of the ligated side
      (left: 23.14 +/- 1.21 micrograms g-1) as compared to the side without ligature
      (right: 23.5 +/- 1.45 micrograms g-1, n = 8, NS). There was no elevation of
      vascular permeability of gingivomuscosal tissue around the ligation in rats
      pretreated with capsaicin either in newborn age (right: 23.92 +/- 1.76 micrograms
      g-1; left (ligature): 23.51 +/- 2.16 micrograms g-1, n = 8, NS) or in adult age
      (right: 20.61 +/- 1.62 micrograms g-1; left (ligature): 20.85 +/- 1.07 micrograms
      g-1, n = 8, NS). Light microscopical studies of oral mucosa revealed, that 8 and
      14 days after the ligature placed around the mandibular left 1st molar of the
      rat, there resulted an accumulation of inflammatory cells in the connective
      tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7806677
TI  - Periodontal regeneration of human infrabony defects (V). Effect of oral hygiene
      on long-term stability.
AB  - The aim of this investigation was to assess the role of supportive periodontal
      care in the maintenance of clinical attachment gained, after surgical treatment
      according to the principles of GTR, in deep infrabony defects. Following GTR
      treatment, 40 deep infrabony defects in 23 patients gained 4.1 mm of probing
      attachment level (PAL) after 1 year of stringent plaque control. In the
      subsequent 3 years, 15 patients (22 sites, group A) were recalled every 3 months.
      In this group, the gained attachment level remained stable. Conversely, 8
      patients (18 sites, group B), who received only sporadic care, lost at 4 years,
      2.8 +/- 2.7 mm of the PAL gained at 1 year. Group A patients had significantly
      lower full mouth plaque and bleeding scores than group B at 4 years. Furthermore,
      detection of bleeding on probing, plaque, P. gingivalis and P. intermedia was
      significantly more frequent in regenerated sites of group B patients. Risk
      assessment analysis indicated that GTR sites in patients receiving only sporadic
      care had a 50-fold increase in risk of PAL loss between 1 and 4 years with
      respect to patients undergoing regular recall. It was concluded that stability of
      gained clinical attachment was dependent upon stringent oral hygiene.

PMID- 7806678
TI  - The reliability of furcation measurements.
AB  - The furcation involvement of 100 molars in 25 patients suffering from moderate to
      advanced periodontitis was investigated. Presurgically, the horizontal probing
      attachment level (PAL-H) within the furcations was assessed 2 x within 14 days.
      To determine the measurement error of PAL-H, the standard deviation of single
      measurements was calculated. The measurements were repeated intrasurgically and
      compared with presurgical assessments of furcation degrees. The overall standard
      deviation of single measurements was 0.739 mm. For buccal, lingual, mesiolingual
      and distolingual furcations, the standard deviations were 0.602 mm, 0.559 mm,
      0.759 mm, 1.099 mm, respectively; measurement error was less in buccal and
      lingual furcations than in distolingual furcations (p < 0.001). The agreement of
      replicate measurements of furcation degrees was excellent for buccal, lingual and
      mesiolingual furcations (weighted k - coefficients between 0.776 and 0.944), but
      only moderate for distolingual furcations (kw = 0.706). Multiple linear
      regression analysis revealed significant influence of furcation depth, width and
      furcation location on differences of PAL-H (p < 0.05). There was no significant
      difference between furcation degree as assessed presurgically and
      intrasurgically.

PMID- 7806679
TI  - Diagnosis of periodontal disease activity by detection of key microbial antigens.
AB  - This paper reviews the development of various rapid microbial identification
      techniques and their potential role in the diagnosis of active periodontal tissue
      destruction. It also explores the concerns expressed by some, that although these
      techniques offer enormous promise as research tools, validation and translation
      of test results to clinical diagnosis, prognosis and treatment planning are still
      problematic. It may be premature to recommend these tests to clinicians in
      practice. Further longitudinal studies are required to establish the best use of
      these techniques in a clinical setting.

PMID- 7806680
TI  - Epithelial remnants in the crestal periodontium of the deciduous and permanent
      dentition of beagle dogs.
AB  - The purpose of this study was to document and characterize epithelial remnants
      (EPRs) of the crestal periodontium of the deciduous dentition of a diphyodont and
      compare them with EPR units found in the corresponding area of the permanent
      dentition. 7 beagle dogs were used. At the age of 10 weeks (deciduous dentition)
      and 15 months (permanent dentition), respectively, a 6-week plaque control period
      was initiated. At the end of each plaque control period, biopsies were obtained
      from the mandibular 02P, 03P (deciduous dentition) and P3, P4 (permanent
      dentition) premolar regions and prepared for histologic analysis. 2 regions, (1)
      the supracrestal region and (2) the periodontal ligament region, were identified.
      The supracrestal region was divided into 4 compartments of equal height. The
      histologic parameters studied included the (i) EPR frequency: number of EPRs/mm
      of root length, (ii) EPR size, (iii) EPR-root distance, (iv) EPR-bone distance
      and (v) cell area. No differences were observed between the 2 dentitions with
      respect to the number, size and relative location of EPR units in the
      supracrestal regions or the periodontal ligament regions. Epithelial remnants of
      the supracrestal region in both dentitions tended to be more frequent, larger and
      positioned further from the root surface than the EPRs of the periodontal
      ligament region. EPR units of the periodontal ligament region were located
      significantly further from the bone in the deciduous dentition than in the
      permanent dentition. The cell area of EPRs did not differ between the 2
      dentitions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7806681
TI  - Treatment of subjects with refractory periodontal disease.
AB  - The aim of the present study was to evaluate the effect of non-surgical
      periodontal therapy with the adjunct of a selected antibiotic in subjects
      diagnosed with refractory periodontal disease. 21 subjects were selected for the
      study; all had a history of periodontal surgery, tetracycline therapy, and
      regular maintenance by a periodontist. When disease activity was detected, a
      bacterial sample was taken and a whole plaque susceptibility test was performed.
      Before the outcome of the susceptibility test the subjects were assigned to
      either antibiotic or placebo therapy. All subjects received scaling and
      rootplaning prior to antibiotic or placebo therapy. Based on the susceptibility
      test, subjects in the antibiotic group were treated either with Augmentin or
      clindamycin. The results demonstrated that in subjects with refractory
      periodontal disease there was no significant difference (N.S.) in the proportion
      of sites losing attachment before and after treatment (11.3% and 12.4%,
      respectively) over a 2-year post therapy observation period. However, the
      proportion of sites showing gain of attachment increased from 0.9% before therapy
      to 5.1% (p = 0.029) following selective antibiotic therapy when combined with
      scaling and rootplaning. The remainder of sites showed no change between pre- and
      post-therapy monitoring periods. The progression of attachment loss in the active
      sites could not be completely stopped over the entire 2-year period. After 12-15
      months following therapy, there was a tendency towards new loss of attachment and
      an increase of pocket depth. However, all 4 subjects treated with placebo drug
      demonstrated continuous deterioration and had to be retreated. Although the
      proportion of sites losing attachment decreased from 5.1% to 2.3% (N.S.), the
      proportion of sites gaining attachment also decreased from 2.0% to 1.0% (N.S.).
      The results suggest that scaling and rootplaning together with selected
      antibiotic therapy repeated every 12-15 months may be beneficial for these
      subjects although it may not completely stop progressive attachment loss.

PMID- 7806682
TI  - The effect of porcelain laminate veneers on gingival health and bacterial plaque
      characteristics.
AB  - The aim of this study was to evaluate the response of microbial plaque and
      gingival inflammation to the placement of porcelain laminate veneers on anterior
      teeth. 9 patients, 7 female and 2 male (mean age of 30 years), with a total of 35
      veneers were examined. The volume of gingival crevicular fluid (GCF), level of
      neutral proteolytic enzyme activity, gingival index (GI), plaque index (PlI) and
      plaque bacteria vitality were measured at baseline and after the placement of
      veneers. The volume of GCF increased after the placement of veneers (p = 0.03).
      No statistically significant differences were found in proteolytic enzyme
      activity or GI (p > 0.05). There were statistically significant reductions in PlI
      (p = 0.000) and plaque bacteria vitality (p = 0.018). Further research is
      required to assess the long-term influence of porcelain laminate veneers on
      gingival health and microbial plaque characteristics.

PMID- 7806683
TI  - Efficacy of interdental cleaning devices.

PMID- 7806684
TI  - Haloperidol: therapeutic window in schizophrenia.
AB  - Twenty-two schizophrenic inpatients were treated for 3 weeks with three randomly
      fixed oral doses of haloperidol (10, 20, or 30 mg). Analysis of the results by a
      nonlinear regression model revealed a curvilinear relationship between
      haloperidol levels in plasma and clinical response, as assessed on the Brief
      Psychiatric Rating Scale (pseudo-R2 = 0.85, F = 17.7, p < 0.001, correlation
      between coefficients ranged from 0.99 to -0.52). This curve defines roughly three
      drug level ranges (low, < 5.5 ng/ml; optimal, 5.5 to 14.4 ng/ml; and high or
      toxic, > 14.4 ng/ml), which are significant for clinical practice. Patients with
      high levels improve to a lesser extent or even worsen in negative symptoms,
      showing a nonstatistically significant trend to present more extrapyramidal
      symptoms. Our data thus support the existence of a therapeutic window for
      haloperidol. Schizophrenic patients with acute exacerbation and drug levels in
      this range would have a greater probability of global clinical improvement.

PMID- 7806685
TI  - Neurologic factors predict a favorable valproate response in bipolar and
      schizoaffective disorders.
AB  - The hypothesis that neurologic factors influence the response to valproate
      (divalproex sodium) in bipolar and schizoaffective disorders was tested. In 115
      predominantly lithium-refractory inpatients, neurologic findings were recorded,
      and blind raters assessed valproate response from the medical record. Patients
      with a seizure history were much more likely to have a robust response to
      valproate (70%), when compared with patients without such history (34.6%).
      History of head injury and abnormal electroencephalographic findings also tended
      to be more common in those patients with good response. Overall, the group of
      patients with any neurologic abnormality exhibited a significantly higher rate of
      good response to valproate (43.6%) than did the neurologically normal group
      (24.3%). Bipolar or schizoaffective patients with abnormal neurologic features
      may represent a distinct subtype of illness and appear to be good candidates for
      valproate therapy.

PMID- 7806686
TI  - A double-blind, placebo-controlled, multicenter study with alprazolam and
      extended-release alprazolam in the treatment of panic disorder.
AB  - This is a double-blind, placebo-controlled, flexible-dose, multicenter, 6-week
      study comparing regular alprazolam (compressed tablet, CT), given four times per
      day, and extended release alprazolam (XR), given once in the morning. The aim of
      the XR preparation is to offer less frequent dosing and to reduce interdose
      anxiety. Of the intent-to-treat group of 209 patients, 184 completed 3 weeks of
      medication and were evaluated according to protocol. There was a completer rate
      for the 6 weeks of 94% (CT), 97% (XR), and 87% (placebo). On global measures,
      Hamilton Rating Scale for Anxiety, phobia rating, and work disability measures,
      both active treatment groups were equally effective and significantly more
      efficacious than the placebo cell on endpoint MANOVA analysis. On analysis of the
      panic factor with endpoint data, both active treatment groups were equally
      effective throughout the 6-week trial and significantly more efficacious than the
      placebo group. Drowsiness occurred more frequently with CT alprazolam (86% of
      patients) than with the XR preparation (79%) or placebo (49%).

PMID- 7806687
TI  - Long-term safety and clinical acceptability of venlafaxine and imipramine in
      outpatients with major depression.
AB  - The antidepressant efficacy and safety of venlafaxine was shown previously in 6
      week, placebo-controlled trials. We evaluated the long-term safety and clinical
      acceptability of venlafaxine and imipramine in a double-blind, parallel-group,
      comparative study. Two hundred ninety depressed outpatients were treated with
      venlafaxine, and an additional 91 received imipramine for as long as clinically
      necessary, up to 1 year. The total daily dose of each drug could vary from 75 to
      225 mg. The Clinical Global Impressions Scale and a therapeutic response rate
      that was based on Clinical Global Impressions Scale-Improvement and incorporated
      discontinuation information were used to evaluate efficacy. Safety determinations
      and patient subjective ratings were used to evaluate safety and clinical
      acceptability. During the study, the adverse events were generally mild to
      moderate and most subsided with continued treatment; the most frequent were
      nausea for venlafaxine and dry mouth for imipramine. The anticholinergic side
      effect burden was significantly higher in the imipramine group than in the
      venlafaxine group. Venlafaxine was judged significantly more acceptable than
      imipramine, on the basis of the subjective ratings by patients. Fewer venlafaxine
      treated patients than imipramine-treated patients withdrew because of adverse
      events and unsatisfactory response. There was a consistent trend in the
      therapeutic response rates in favor of venlafaxine that reached statistical
      significance at months 2, 6, and 12. In this long-term study, patient
      acceptability was greater for venlafaxine than for imipramine, suggesting
      therapeutic advantages for venlafaxine in the long-term treatment of depression.
      Additional studies with other active comparators are underway to confirm and
      extend these encouraging results.

PMID- 7806688
TI  - Relationship of lithium concentrations in the brain measured by lithium-7
      magnetic resonance spectroscopy to treatment response in mania.
AB  - Lithium concentrations in the brain were measured in 14 manic patients with
      bipolar disorder (12 with bipolar disorder, manic, and 2 with bipolar disorder,
      not otherwise specified, by DSM-III-R) by the use of lithium-7 magnetic resonance
      spectroscopy ([7Li]MRS). The reduction of Petterson Mania Rating Scale 4 weeks
      after the initiation of lithium treatment was not significantly correlated with
      concentrations in serum (r = 0.33), but was correlated with concentrations in the
      brain (r = 0.64; p < 0.05). These results suggest that the treatment response to
      lithium in manic patients with bipolar disorder is more closely related to the
      lithium concentration in the brain as measured by [7Li]MRS than to the
      concentration in serum.

PMID- 7806689
TI  - Lithium- and carbamazepine-associated sinus node dysfunction: nine-year
      experience in a psychiatric hospital.
AB  - The cardiac effects of lithium and carbamazepine are considered rare, but both
      are known to induce sinus node dysfunction. The author presents the 9-year
      experience in a state mental hospital with lithium-induced sinus node
      dysfunction. Four of the five patients were also on carbamazepine. The clinical
      features of previously reported cases of lithium- and carbamazepine-associated
      sinus node dysfunction are reviewed. A role for carbamazepine in lithium-induced
      sinus node dysfunction is discussed.

PMID- 7806690
TI  - Coadministration of fluvoxamine increases serum concentrations of haloperidol.
AB  - Four patients with chronic schizophrenia were treated with a combination of
      fluvoxamine, haloperidol, and benztropine. The combination significantly impaired
      performance on tests of delayed recall memory and attentional function.
      Haloperidol concentrations in serum were monitored in three patients and were
      robustly elevated by fluvoxamine.

PMID- 7806691
TI  - The brief psychiatric rating scale: effect of scaling system on clinical response
      assessment.
AB  - The Brief Psychiatric Rating Scale (BPRS) is an 18-item rating scale frequently
      used to assess change in psychopathology in schizophrenic patients in
      antipsychotic drug trials. BPRS items may be rated by the use of either a 1 to 7
      or 0 to 6 scaling system, with the 1 or 0 rating indicating no pathology,
      respectively. When percent change in BPRS total score is used as an index of
      change, measurement considerations indicate that the 0 to 6 scaling system is
      preferable. Furthermore, when the 1 to 7 scaling system is used, patients whose
      initial BPRS values fall at the lower end of the range are classified as
      responders at a lower rate than are patients with higher initial scores. The
      adoption of the 0 to 6 scaling system for the BPRS and other rating scales, such
      as the Positive and Negative Syndrome Scale, is advocated.

PMID- 7806692
TI  - Gepirone treatment of atypical depression: preliminary evidence of serotonergic
      involvement.
AB  - This is a report of a controlled trial of gepirone, a 5-hydroxytryptamine (5
      HT1A) partial agonist azapirone related to buspirone, in the treatment of
      atypical depression. The azapirones are of particular interest because their
      highly selective actions on the serotonergic system may possibly make them useful
      pharmacologic probes and potentially selective therapeutic agents. Sixty
      outpatients meeting Columbia criteria for definite or probable atypical
      depression were enrolled in a double-blind, randomized, placebo-controlled, 8
      week clinical trial at a single site. The dosage schedule was fixed flexible,
      with 10-mg capsules given on a thrice-daily schedule, with doses of up to 120 mg
      daily. The response rate at 8 weeks for the intention-to-treat sample analyzed
      with the last observation carried forward was 62% (18 of 29 patients) for
      gepirone and 20% (6 of 30 patients) for placebo (chi 2 = 9.1; df = 1; p < 0.001).
      Robust and consistent drug-placebo differences are seen across virtually all
      rating scales post-treatment. The effect of gepirone was consistent across the
      levels of concomitant variables, including duration of episode and presence of
      dysthymia or panic. Gepirone is a novel antidepressant that holds promise for the
      treatment of atypical depression and that may be of heuristic value because of
      its relatively specific actions on the serotonergic system.

PMID- 7806693
TI  - A prospective study of lithium augmentation in antidepressant-resistant geriatric
      depression.
AB  - This open, prospective study investigated the efficacy of lithium augmentation in
      elderly patients who had failed to respond to a 6-week course of antidepressant
      medication. Twenty-one patients (age range, 64 to 88 years) with DSM-III-R
      unipolar, nonpsychotic major depression refractory to a 6-week course of
      nortriptyline, fluoxetine, or phenelzine underwent a minimum of 2 weeks of
      lithium augmentation. Five patients had a complete response, 3 had a partial
      response, and 13 did not respond. Half of the patients developed dose-limiting
      side effects, most commonly neuromuscular or neurologic. Patients developing side
      effects were significantly older (p = 0.05), and there was a tendency for side
      effects to occur more frequently in patients treated with fluoxetine. The rate of
      response to lithium augmentation in this elderly population was lower than that
      reported for most open and controlled studies in younger patients. Possible
      reasons for this are discussed.

PMID- 7806694
TI  - Neutropenia with clozapine and methazolamide.

PMID- 7806695
TI  - Sertraline treatment of attention deficit hyperactivity disorder and Tourette's
      syndrome.

PMID- 7806696
TI  - Fluoxetine for cocaine dependence in methadone maintenance.

PMID- 7806697
TI  - Precipitation of a psychoneuromotor syndrome by fluoxetine in a haloperidol
      treated schizophrenic patient.

PMID- 7806698
TI  - A naltrexone-induced increase in insulin requirement.

PMID- 7806699
TI  - The verdant octogenarian.

PMID- 7806700
TI  - Diseases due to Campylobacter, Helicobacter and related bacteria.

PMID- 7806701
TI  - Congenital infection of pigs with ruminant-type pestiviruses.
AB  - Congenital infections of pigs were induced with two ruminant-type pestiviruses
      isolated from pigs. One of the viruses was bovine viral diarrhoea virus-like and
      the other border disease virus-like. Both produced symptoms similar to those
      observed with low virulence strains of classical swine fever virus. A striking
      effect of persistent virus infection in post-natal life was stunting in viraemic
      animals. It was also shown that a congenitally infected pig shed virus for 2.5
      years and in sufficient quantity to infect other pigs, even by indirect contact.
      Unlike ruminants, congenitally infected pigs sometimes had persistent viraemia
      but eventually eliminated the virus. Clearance of virus from the blood was
      related to the appearance of neutralizing antibodies. However, clearance from the
      tissues sometimes took as much as 5 months longer than from the blood.

PMID- 7806702
TI  - Histopathological changes in lymph nodes of cats experimentally infected with the
      feline immunodeficiency virus (FIV).
AB  - Twelve specific-pathogen-free (SPF) kittens aged 8-12 weeks were serially
      infected in pairs every 6 weeks, by the intraperitoneal route, with the feline
      immunodeficiency virus (FIV). Three additional SPF kittens were kept as controls.
      The infected animals were killed 10 weeks after inoculation, during the primary
      phase of the FIV infection. Generalized lymphadenopathy (GL) was observed in the
      first three pairs of cats. All lymph nodes examined from the 12 infected cats
      showed histological changes. These included severe follicular hyperplasia with
      hyperactive follicular centres (FCs) which were either (1) naked, (2) infiltrated
      by lymphocytes, (3) seen to contain islets of lymphocytic mantle cells, or (4)
      disrupted by lymphocytes. The presence of both CD4+ and CD8+ T lymphocytes was
      demonstrated in the FCs immunocytochemically. The distribution of CD4 lymphocytes
      resembled that in control lymph nodes, but the CD8 cells were increased in number
      and either scattered or clustered in the follicles. In addition, varying degrees
      of interfollicular proliferation and medullary plasmacytosis were observed in the
      lymph nodes. These findings, which were common to all infected animals,
      represented distinct prodromal manifestations of FIV infection. The changes in
      lymphocyte subpopulation distribution observed in early FIV infection were
      reminiscent of findings encountered in human immunodeficiency virus (HIV)
      infection and reinforce the suggestion that FIV infection is an appropriate model
      for the study of HIV pathogenesis.

PMID- 7806703
TI  - Mucoid dysplasia of tricuspid and congenital bicuspid aortic valves in Syrian
      hamsters (Mesocricetus auratus).
AB  - A histological study was made of the aortic valves of 141 Syrian hamsters aged
      between 35 and 657 days, belonging to an inbred laboratory colony with a high
      incidence of congenital bicuspid aortic valves. A tricuspid aortic valve was
      found in 81 specimens, whereas the remaining 60 possessed a bicuspid aortic
      valve. In all bicuspid valves there were two aortic sinuses, a ventral and a
      dorsal, each supporting one cusp. Thirty-three (23.4%) of the 141 specimens
      showed mucoid dysplasia of the aortic valve. The defect was characterized by
      thickening of the valve cusps and disruption of the fibrosa layer accompanied by
      an increased amount of glycosaminoglycans. Ten (12.3%) of the 81 tricuspid aortic
      valves and 23 (38.3%) of the 60 bicuspid aortic valves were dysplastic. This
      difference was statistically significant (P < 0.001). The findings indicate that,
      in the Syrian hamster, the simultaneous occurrence of bicuspid aortic valve and
      aortic valve dysplasia is not a random event. However, the fact that these valve
      defects also occur independently suggests that there is no primary morphogenetic
      dependence between them, but that some other cause predisposes to their
      concurrence.

PMID- 7806704
TI  - Hyaluronan in canine arthropathies.
AB  - Soluble hyaluronan (HA), which has been considered as a marker for joint disease
      in man, was measured in serum and synovial fluid (SF) from dogs with
      osteoarthritis (OA), rheumatoid arthritis (RA), and rupture of the cranial
      cruciate ligament (CCL) and from normal dogs (control). Dogs with OA and RA had
      significantly increased serum HA (P < 0.001) and decreased synovial fluid HA (P <
      0.001), as did dogs with CCL rupture (serum, P < 0.05; synovial fluid, P <
      0.005). In OA, HA was lower in the SF from the affected joint than in that from
      the clinically normal (inactive) contralateral joint; no such difference was seen
      in dogs with CCL rupture. Dogs with liver disease (portocaval shunts, viral
      infectious hepatitis, metastatic neoplasm and disease secondary to diabetes
      mellitus) had increased serum HA concentrations (P < 0.001). There was a
      significant overlap of HA values in the diseased and normal dogs. Therefore, it
      is unlikely that the measurement of this cartilage breakdown product would be of
      value for diagnosis or prognosis in canine arthropathies.

PMID- 7806705
TI  - Fate of herpesvirus DNA in embryos and tadpoles cloned from Lucke renal carcinoma
      nuclei.
AB  - The Lucke renal carcinoma of the northern leopard frog, Rana pipiens, has a
      herpesvirus aetiology. Lucke tumour nuclei inserted into enucleated frogs' eggs
      produce development to the swimming tadpole stage. Tissue from these tumour
      nuclear transplant animals can be induced to survive and differentiate further by
      allografting to normal tadpoles. We wished to ascertain whether the aetiological
      agent, the Lucke tumour herpesvirus (LTV), persists in the animals produced by
      tumour nuclear transplantation. The polymerase chain reaction was used to amplify
      a 1.2 kbp Hind III restriction fragment of LTV DNA in whole animal homogenates
      prepared from tumour nuclear transplant tadpoles and normal tadpoles fertilized
      in vitro. The LTV fragment was not present in the majority (31 of 34) of the
      cloned animals derived from tumour nuclei, nor was it present in any of five
      normal tadpoles. Either the 1.2 kbp fragment of LTV DNA was eliminated from most
      of the cloned animals during the massive reprogramming of the neoplastic genome
      initiated by insertion of the tumour nuclei into egg cytoplasm, or the nuclei
      selected for transplantation were primarily those lacking this fragment of LTV
      DNA. The limited development of the tumour nuclear tadpoles was probably not due
      to the presence of these viral sequences, but rather reflected the limited
      plasticity of the tumour cell genome as assayed by nuclear transplantation.
      Failure to detect the 1.2 kbp fragment of LTV DNA in the majority of mitotic
      progeny of the Lucke tumour genome does not imply that other parts of the viral
      genome do not persist.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7806706
TI  - Pathology of equine pneumonia associated with transport and isolation of
      Streptococcus equi subsp. zooepidemicus.
AB  - Seven horses that died of pneumonia associated with transport yielded
      Streptococcus equi subsp. zooepidemicus (S.z.) from their pulmonary lesions.
      These lesions were divisible roughly into two types, serous haemorrhagic
      pneumonia and multiple foci of coagulative necrosis, which were considered to
      reflect a temporal difference in the process of lesion formation.
      Immunohistologically, S.z. antigen was detected in both types of lesion. Acute
      necrotic lacunar tonsillitis was considered to play an important role in the
      onset of the pneumonia.

PMID- 7806707
TI  - Spontaneous vascular mineralization in the brains of cows.
AB  - The frequency of occurrence and the characteristics of vascular mineralization in
      the brains of cows were studied. Mineralized lesions were found in the pallidal
      arteries in eight of 13 cows. They appeared as basophilic deposits in the
      arterial walls, were sheath-like or tubular in shape, and were accompanied by
      intimal oedema or fibrous thickening. The deposits were positive for periodic
      acid-Schiff, von Kossa's, alizarin red and Berlin blue stains. Elemental analysis
      revealed the presence of large amounts of phosphorus, calcium and zinc, as well
      as small amounts of iron, copper and sodium.

PMID- 7806708
TI  - Anxiety and depression in children and adolescents: negative affectivity and the
      utility of self-reports.
AB  - Self-reported depression and anxiety were examined in 233 inpatient children
      diagnosed with either an anxiety disorder or a depressive disorder. Depressed
      children reported more problems related to a loss of interest and low motivation,
      and they had a more negative view of themselves. Anxious children reported more
      worry about the future, their well-being, and the reactions of others. The groups
      did not differ in the degree of depressed affect reported in terms of being sad,
      lethargic, bothered by things, or feeling alone and isolated. These findings
      suggest that a general negative affectivity component is common to both anxiety
      and depression disorders and measures. The results demonstrate that anxiety and
      depression in children have distinguishing features that can be measured by
      common self-report instruments, and the findings indicate that 1 factor that may
      distinguish between anxiety and depression in children is positive affectivity.

PMID- 7806709
TI  - Patterns of symptomatic recovery in psychotherapy.
AB  - Using the psychotherapy dosage model in which effect was probability of recovery,
      this study compared treatment response rates for psychological symptoms. Symptom
      checklists were administered to 854 psychotherapy outpatients at intake and
      during treatment. Sixty-two symptoms were grouped into 3 classes on the basis of
      probit analysis results. Chronic distress symptoms demonstrated the fastest
      average response rate, whereas characterological symptoms demonstrated the
      slowest. Acute distress symptoms showed the highest average percentage of
      patients recovered across doses. A typical outpatient needed about a year of
      psychotherapy to have a 75% chance of symptomatic recovery. The model holds
      promise for establishing guidelines for the financing of psychotherapy.

PMID- 7806710
TI  - Diagnostic accuracy of the Child Behavior Checklist scales for attention-deficit
      hyperactivity disorder: a receiver-operating characteristic analysis.
AB  - The diagnostic accuracy of the Child Behavior Checklist (CBCL) scales for
      attention-deficit hyperactivity disorder (ADHD) were examined using receiver
      operating characteristic (ROC) analysis. Three logistic regression models were
      estimated in an initial sample of 121 children with and without ADHD. These
      models were then tested in a cross-validation sample (N = 122) and among the 111
      brothers and 108 sisters of the initial and cross-validation samples. In all four
      groups, the CBCL Attention Problems scale had the highest discriminating power
      for ADHD. Adding other scales did not increase the area under the curve of the
      ROC significantly. These findings suggest that the CBCL Attention Problems scale
      could serve as a rapid and useful screening instrument not only to help identify
      cases likely to meet criteria for ADHD in clinical settings but also to identify
      cases of ADHD among the siblings of children with ADHD.

PMID- 7806711
TI  - Changes in premenstrual symptoms and irrational thinking following cognitive
      behavioral coping skills training.
AB  - Women reporting severe premenstrual symptoms were allocated nonrandomly to a
      cognitive-behavioral coping skills treatment (n = 13), a nonspecific treatment (n
      = 12), or a waiting-list group (n = 12). Repeated measures analyses of variance
      showed that, compared with control subjects, the coping skills group reported
      significant reductions in premenstrual symptomatology and irrational thinking at
      posttreatment and at 9-month follow-up. There were no significant differences
      between the waiting-list and control intervention groups at any time of testing.
      It was suggested that the increased irrationality reported at pretreatment should
      be viewed not as a "cause" of premenstrual problems but as a product of the
      stresses experienced in the premenstruum phase. The findings of this study
      indicated that cognitive-behavioral coping skills treatments can reduce the
      negative effects of premenstrual symptoms and that those reductions can be
      maintained over time.

PMID- 7806712
TI  - Intimate relationships and depression: is there a causal connection?
AB  - The causal pathways that link depression and dissatisfaction in intimate
      relationships were estimated in 115 patients during the first 12 weeks of
      treatment with cognitive-behavioral therapy for depression. Depression severity,
      as measured by the Beck Depression Inventory, was negatively correlated with
      relationship satisfaction at intake and at 12 weeks. However, structural equation
      modeling was not consistent with the hypothesis that depression severity has a
      causal effect on relationship satisfaction levels and suggested that relationship
      satisfaction may have only a weak reciprocal effect on depression severity. As
      predicted, married patients were substantially less depressed 12 weeks after the
      beginning of treatment, when controlling for initial depression severity.
      Contrary to expectations, marital status predicted improvement even when
      relationship satisfaction was controlled. Unexpectedly, dysthymia at intake was
      associated with low relationship satisfaction after 12 weeks, when initial
      relationship satisfaction was controlled, suggesting that chronic, low-level
      depression may have a stronger association with interpersonal problems than other
      forms of depression, such as major depressive episodes. The theoretical and
      clinical implications of the findings are discussed.

PMID- 7806713
TI  - Physically aggressive boys from ages 6 to 12: family background, parenting
      behavior, and prediction of delinquency.
AB  - Boys from low socioeconomic environments were rated on physical aggression at
      ages 6, 10, 11, and 12 by teachers and classified according to stability of
      fighting over time: stable high fighters, high fighters with late onset,
      desisting high fighters, variable high fighters, and nonfighters. The fighter
      groups differed from each other both in family background and parenting behavior.
      They were also significantly associated with delinquency across ages 10 to 14. A
      stepwise logistic regression with fighter groups, family adversity index, and
      parenting behavior variables as predictors showed that the Punishment x Fighter
      Group interaction, together with supervision, predicted self-reported
      delinquency. The study thus showed that the developmental pathways of physically
      aggressive behavior for boys in low socioeconomic environments were related to
      familial adversity and poor parenting, and that they predicted delinquency.

PMID- 7806714
TI  - Sensation seeking, substance abuse, and psychopathology in treatment-seeking and
      community cocaine abusers.
AB  - Sensation seeking, substance abuse severity, and psychiatric disorders were
      systematically assessed in a clinical and a community sample of 335 cocaine
      abusers. In contrast to low-sensation-seeking cocaine abusers, high-sensation
      seekers exhibited more severe symptoms of substance abuse, exhibited more severe
      psychosocial impairment, were more likely to be polysubstance abusers, and had an
      earlier age of onset for substance use and abuse. High-sensation seekers were
      more likely to report both a lifetime history and family history of antisocial
      personality, attention deficit disorder, and conduct disorder. Sensation seeking
      was related to several dimensions that are important for defining subtypes of
      substance abusers and was consistent with other features of a Type II
      classification.

PMID- 7806715
TI  - Chronic low back pain: toward an integrated psychosocial assessment model.
AB  - This study reports on the integration of 6 dimensions of chronic low back pain to
      provide a multidimensional profile of the patient. These dimensions were pain
      intensity, functional disability, attitudes toward pain, pain coping strategies,
      depression, and illness behavior. Cluster analysis of the data obtained from 100
      patients with chronic low back pain revealed the presence of 3 distinct patient
      groups: patients who were in control, patients who were depressed and disabled,
      and patients who were active copers with high denial. The validity of these
      clusters was supported by significance testing on several external variables.

PMID- 7806716
TI  - Dangerousness: assessing the risk of violent behavior.
AB  - Results of discriminant analyses for identifying dangerous inpatients and prison
      inmates are presented. Analysis of a hospital sample (N = 100) yielded a
      discriminant function containing 5 variables, which was 85% accurate in
      classifying the sample. Analysis of a prison sample (N = 100) yielded a
      discriminant model with 6 variables, which was 72% accurate in classifying the
      sample. Stepwise discriminant analysis of the combined hospital and prison
      derivation sample (N = 200) yielded a discriminant function containing 8
      variables, which was 75% accurate in classifying the sample as dangerous or
      nondangerous. It was concluded that the derived population-specific (i.e.,
      hospital or prison) models constitute empirically valid measures of dangerousness
      for the populations studied.

PMID- 7806717
TI  - Dropping out of child psychotherapy: distinguishing early and late dropouts over
      the course of treatment.
AB  - The present study examined child, parent, and family factors that predict
      dropping out from therapy among children (ages 4-13) referred for the treatment
      of oppositional, aggressive, and antisocial behavior. It was proposed that
      factors predicting attrition would vary as a function of whether families dropped
      out early or late in treatment. Several factors related to family (e.g.,
      socioeconomic disadvantage, adverse child-rearing practices), parent (e.g.,
      stress, life events, history of antisocial behavior), and child functioning
      (e.g., severity and chronicity of antisocial behavior, lower IQ, peer relations)
      predicted premature termination from treatment. A different pattern was evident
      in the factors predicting early and late termination from therapy. The findings
      have implications for conceptualizing the process of engaging and retaining
      families in treatment and for preventing premature termination.

PMID- 7806718
TI  - Introduction to special section: the role of longitudinal data with child
      psychopathology and treatment: preliminary comments and issues.
AB  - Longitudinal data can play an important role in child psychopathology and
      treatment. This article introduces a review of some of the research questions
      that longitudinal designs can answer and how longitudinal studies have been used
      in evaluating traditional syndromes in child clinical psychology. We then
      introduce the articles in this special section.

PMID- 7806719
TI  - Problems and solutions in longitudinal and experimental treatment studies of
      child psychopathology and delinquency.
AB  - This article identifies questions in child psychopathology and delinquency that
      can best be answered by using longitudinal data and discusses the advantages and
      problems of longitudinal studies. The article also reviews methodological issues
      arising in longitudinal research on child psychopathology and proposes solutions
      to problems. Retrospective and prospective designs are contrasted with the
      accelerated longitudinal design. It is concluded that more longitudinal studies
      of child psychopathology including experimental treatment interventions are
      needed, with repeated data collection from a variety of sources and several years
      of data before and after the interventions. Such studies, in addition to the
      traditional longitudinal studies, are likely to improve the understanding of
      child psychopathology and of factors that influence and reduce serious outcomes
      for children and adolescents.

PMID- 7806720
TI  - Diagnosis, assessment, and treatment of externalizing problems in children: the
      role of longitudinal data.
AB  - Prospective longitudinal studies that pertain to the stability, developmental
      pathways, and long-term outcome for the 2 primary forms of externalizing behavior
      problems (conduct problems [CP] and hyperactivity [HA]) are described. Treatment
      outcome studies for CP and HA with at least 1 year of follow-up data are
      reviewed. The implications of longitudinal research for the diagnosis,
      assessment, and treatment of externalizing behavior problems in children are
      discussed. Greater attention must be paid to issues related to comorbidity,
      developmentally appropriate assessments, and long-term outcome of interventions.
      Longitudinal-experimental investigations that serve to delineate developmental
      pathways as well as assess the effects of developmentally sensitive,
      comprehensive interventions are recommended.

PMID- 7806721
TI  - Diagnosis, assessment, and treatment of internalizing problems in children: the
      role of longitudinal data.
AB  - This review examines the role of longitudinal data in the diagnosis, assessment,
      and treatment of internalizing disorders in children and adolescents. On the
      basis of the limited longitudinal data available, it is suggested that
      internalizing disorders in children and adolescents are highly prevalent,
      frequently comorbid with other childhood disorders, and, arguably so, persistent
      over time. However, it is also noted that a considerable amount of instability
      characterizes these disorders and that the developmental course is not fully
      understood at this time. In addition, these disorders are responsive to
      treatment, at least on a short-term basis. Finally, a plea is made for
      longitudinal studies that use a developmental perspective in examining
      internalizing disorders in children and adolescents.

PMID- 7806722
TI  - Beyond longitudinal data: causes, consequences, changes, and continuity.
AB  - Longitudinal data have very important advantages for both measurement and the
      testing of causal hypotheses on the causes or course of psychopathology, but
      cross-sectional studies should usually be used first. The investigation of causes
      needs to encompass the several different types of causal question. The study of
      within-individual change constitutes a most important research strategy to test
      causal hypotheses, but it is not the only approach. Their testing requires
      specification of possible mechanisms, together with attention to the differential
      impact of risk experiences, of the possible role of person-environment
      interactions and protective mechanisms. This article addresses several strategies
      needed in using longitudinal data to test cause-and-effect relationships,
      including natural experiments, testing of competing hypotheses on mechanisms,
      study of reversal effects, multiple replications in different circumstances, use
      of designs to dissociate possible mechanisms, testing for dose-response
      relationships, examination of effect-specificity, considering biological
      plausibility, and assessing the strength of effects.

PMID- 7806723
TI  - Disabuse of the drug metaphor: psychotherapy process-outcome correlations.
AB  - The drug metaphor suggests that if a process component (e.g., interpretation) is
      an active ingredient of a successful psychotherapy, then administering a
      relatively high level of it should yield a relatively positive outcome, and
      levels of the process component and the outcome should be correlated across
      clients. Measures of 5 theoretically relevant, reliably measured verbal process
      components were compared with the rate of change in 3 standard symptom intensity
      measures across the brief treatments of 39 (mainly depressed) psychotherapy
      clients. The expected significant process-outcome correlations were not found.
      These results are discussed as they illuminate some misleading assumptions that
      underlie many conventional studies of psychotherapy process and outcome.

PMID- 7806724
TI  - Abuse and disabuse of the drug metaphor in psychotherapy research: hold on to the
      baby as you throw out the bath.
AB  - Stiles and Shapiro (1994) argue that trivial correlations between process
      variables and treatment outcome point to inherent methodological limitations of
      correlational designs in process-outcome research. In coming to such a far
      reaching (erroneous) conclusion, Stiles and Shapiro are throwing out the baby
      with the bath. Correlational designs are perfectly appropriate for testing
      process-outcome correlations if process measures are adequately conceptualized.
      Examples of case-specific measures of therapist responsiveness are reviewed to
      illustrate the power of correlational designs.

PMID- 7806725
TI  - Recipes for psychotherapy.
AB  - Stiles and Shapiro (1994) try to make a case for abandoning the model of drug
      research in exploring psychotherapy effectiveness--specifically, the idea that
      psychotherapy can be viewed in terms of effective "ingredients." Although
      provocative, their analysis can be challenged on methodological grounds involving
      failure to use multivariate analytic approaches, incomplete exploitation of
      advantages of growth curve analysis, and lack of attention to issues of
      statistical power. Acceptance of the conclusions proffered by Stiles and Shapiro
      would have negative effects on psychotherapy research and practice, and the case
      against the search for effective elements in psychotherapy process is not yet
      strongly made.

PMID- 7806726
TI  - Drugs, recipes, babies, bathwater, and psychotherapy process-outcome relations.
AB  - In their critiques of Stiles and Shapiro's (1994) discussion of the process
      outcome correlation problem, Silberschatz (1994) and Sechrest (1994) suggested
      that the problem is not fundamental but merely technical. Silberschatz suggested
      that more complex measures would solve the problem; Sechrest suggested that more
      complex analyses would solve the problem. Following Sechrest's multivariate
      suggestions, however, produced no better result. Contrary to Silberschatz's and
      Sechrest's suggestions, the problem is not in the measures or the analyses but in
      the interpretation of the results (null results as well as positive results),
      particularly in a failure to incorporate fully the phenomenon of responsiveness
      into an understanding of process-outcome relations.

PMID- 7806727
TI  - How many subjects to screen? A practical procedure for estimating multivariate
      normal probabilities for correlated variables.
AB  - This article suggests a practical procedure for estimating the number of Ss that
      need to be screened to obtain a sample of fixed size that meets multiple
      correlated criteria. The procedure is based on the fact that least squares
      regression provides a good quadratic fit for Monte Carlo estimates of
      multivariate probabilities when they are plotted as a function of mean pairwise
      correlations (r) for the criterion variables. The equations given here can be
      used to predict selected 3- to 5-variable joint probabilities with reasonable
      accuracy as long as pairwise correlations for the selection criteria range from
      .10 to .90.

PMID- 7806728
TI  - Accounting for case manager effects in the evaluation of mental health services.
AB  - Three methods of accounting for case manager effects in tests of the efficacy of
      mental health services are explored. These methods include (a) treating the case
      manager as a fixed factor, (b) treating the case manager as a random factor, and
      (c) examining service effects within the case manager. They are demonstrated with
      data from a nationally known case management program serving individuals with
      serious and persistent mental illness. Specifically, 3 conceptually distinct
      types of services provided or brokered by case managers are identified:
      habilitation-rehabilitation, community support, and traditional psychiatric
      services. The effectiveness of each in improving clients' adjustment is then
      examined with multiple regression adjustment strategies and each of the 3 methods
      to account for case manager effects. The results provide strong support for
      effects attributable to case managers and some support for the efficacy of
      habilitation-rehabilitation and community support services beyond the effects of
      traditional psychiatric services.

PMID- 7806729
TI  - Predicting mild and severe husband-to-wife physical aggression.
AB  - Nonordered multinomial logistic models were used to estimate the odds of mild and
      severe husband-to-wife physical aggression in 11,870 White men. Being younger,
      having a lower income, and having an alcohol problem significantly increased the
      odds of either mild or severe physical aggression. A drug problem uniquely
      increased the risk of severe physical aggression. Marital discord and depressive
      symptomatology, but not work stress, further increased the odds of both mild and
      severe physical aggression, with martial discord being the most influential
      psychological variable. Compared with mildly physically aggressive men, those who
      were severely physically aggressive earned lower income, were more likely to
      report an alcohol or a drug problem, and had more marital discord and depressive
      symptomatology.

PMID- 7806730
TI  - Affect, verbal content, and psychophysiology in the arguments of couples with a
      violent husband.
AB  - The purpose of this investigation was to study the affect, psychophysiology, and
      violent content of arguments in couples with a violent husband. On the basis of
      self-reports of violent arguments, there were no wife behaviors that successfully
      suppressed husband violence once it began; moreover, husband violence escalated
      in response to nonviolent as well as violent wife behaviors, whereas wife
      violence escalated only in reaction to husband violence or emotional abuse. Only
      wives were fearful during violent and nonviolent arguments. The observational
      coding of nonviolent arguments in the laboratory revealed that both battering
      husbands and their wives (DV) were angrier than their maritally distressed but
      nonviolent (DNV) counterparts. As predicted, on the more provocative anger codes,
      only DV men differed from their DNV counterparts. However, DV wives were as
      verbally aggressive toward their husbands as DV husbands were toward their wives.

PMID- 7806731
TI  - Occupational settings facilitating wisdom-related knowledge: the sample case of
      clinical psychologists.
AB  - Wisdom can be defined as expert knowledge in the fundamental pragmatics of life.
      Examined here is whether clinical practice may facilitate access to and
      acquisition of such knowledge. Spontaneous think-aloud responses to 2 wisdom
      related dilemmas from young (M = 32 years) and older (M = 70 years) clinicians
      were compared with responses obtained from other professionals. Raters judged
      clinicians' responses as higher on 5 criteria of wisdom: factual knowledge,
      procedural knowledge, life-span contextualism, value relativism, and management
      of uncertainty. Contrary to most studies of cognitive aging, young and older
      adults did not differ. Rather, each age-cohort group received highest ratings
      when responding to a life dilemma matched to their own life phase. Discussed is
      the application of a wisdom framework to assessing therapeutic treatment goals
      and therapist interventions as well as global changes in client's beliefs during
      therapy.

PMID- 7806732
TI  - When home caregiving ends: a longitudinal study of outcomes for caregivers of
      relatives with dementia.
AB  - OBJECTIVES: To study caregivers' decisions to end home care for relatives with
      dementia; to study the changes in caregiver functioning over time. DESIGN: A
      prospective longitudinal follow-up study. SETTING: Individual homes and chronic
      care facilities in Montreal. PARTICIPANTS: 157 caregiver-dependent dyads,
      followed up 2 years later; dependents had been diagnosed as having progressive
      dementia. MEASUREMENTS: A standard interview and a series of standardized
      psychological questionnaires were given to caregivers, assessing their
      functioning and their appraisals of the dependent person in their care.
      Dependents received the Mini-Mental State Examination. MAIN RESULTS: Caregivers
      cited patient deterioration as the most common reason for ending home care. Most
      caregivers did not prepare their relative before institutionalization. Most
      caregivers were satisfied with having ended home care and believed the decision
      was positive for themselves and their dependent, but a sizable minority of
      caregivers and dependents had difficulty adjusting to the end of home care.
      Repeated measures multivariate analyses indicated that caregivers who had
      discontinued home care because of placement or death of the dependent had
      improved functioning and quality of life and better health than caregivers still
      providing home care. CONCLUSIONS: Caregivers most frequently cite deteriorating
      patient conditions as the main causes of ending home care. Caregiver exhaustion
      is the single most frequently given reason. Caregivers who were still providing
      home care at the end of the study were functioning less well than caregivers who
      had ended home care, despite having initially functioned at better levels.

PMID- 7806733
TI  - Measuring physical function in community-dwelling older persons: a comparison of
      self-administered, interviewer-administered, and performance-based measures.
AB  - PURPOSE: To compare two self-administered, one interviewer-administered, and one
      performance-based measure of physical function in community-based older persons.
      METHODS: Eighty-three subjects were recruited from meal sites, senior recreation
      centers, and senior housing units for a comprehensive geriatric assessment
      program. At the time of screening, study participants self-administered the
      Functional Status Questionnaire (FSQ) and were administered the Katz Activities
      of Daily Living (ADL) and the Older Americans Resources and Services Instrumental
      Activities of Daily Living (OARS-IADL) instruments by interview. Participants
      also completed the Physical Performance Test (PPT) and were given the Medical
      Outcomes Study SF-36 to self-administer on site or at home and return by mail.
      RESULTS: All 83 subjects completed FSQ, Katz ADL, OARS-IADL, and PPT; 72 returned
      SF-36 forms. Correlations between the two self-administered physical function
      measures (FSQ and SF-36) were higher than between self-administered and
      interviewer-assessed (ADL and OARS-IADL) or performance-based (PPT) measures.
      When assessed for construct validity, the self-administered, OARS, and PPT
      measures had comparable correlations with role limitations as a result of
      physical health problems, but relationships between physical functional status
      measures and other SF-36 measures of health were inconsistent. CONCLUSION: The
      relationships between commonly used self-administered, interviewer-administered,
      and performance-based measures of physical function were inconsistent and weak,
      suggesting that these instruments are not measuring the same construct.

PMID- 7806734
TI  - Does the ECA underestimate the prevalence of late-life depression?
AB  - OBJECTIVE: This research addresses the most frequently cited methodological
      criticism of the Epidemiologic Catchment Area (ECA) surveys--which might lead to
      significantly lower estimates of true prevalence rates for late-life depression-
      the inability of the Diagnostic Interview Schedule (DIS) to distinguish between
      somatic symptoms of depression that result from physical causes and those that
      result from psychiatric causes. DESIGN: The data for this study come from the ECA
      Wave Two surveys sponsored by the National Institute of Mental Health. In this
      analysis, symptoms of depression the respondent always attributed to physical
      causes are recoded to be equivalent to those having a psychiatric cause. The
      third edition of the Diagnostic and Statistical Manual (DSM-III) scoring
      algorithm for depression (i.e., dysphoria plus four of the eight Criterion B
      symptoms) was then applied to the recorded data set. RESULTS: Recording somatic
      symptoms of depression, originally attributed to physical or medical
      explanations, to psychiatric symptoms does not result in a disproportionate rise
      in diagnosable depression in the older age groups. CONCLUSIONS: This analysis
      provides additional support for the ECA survey's prevalence estimate of late-life
      depression. This research failed to find evidence that the highly structured
      nature of the DIS makes it unsuitable for ascertaining symptoms of depression in
      the elderly.

PMID- 7806735
TI  - Acute respiratory illness in older community residents.
AB  - OBJECTIVE: To describe the 3-year incidence of acute respiratory illness in a
      population of noninstitutionalized elderly persons. DESIGN: Cohort analytic study
      with an observation period of 3 years. SETTING: Large midwestern urban community.
      SUBJECTS: 574 noninstitutionalized persons aged 65 years and older, of whom 349
      were living independently, 110 were in congregate settings, and 115 were living
      independently and regularly caring for small children. METHODS: Subjects were
      interviewed and examined by nurse practitioners at intake and every 4 months.
      Acute illness and convalescent visits were made when illnesses were reported by
      participants. MAIN OUTCOME MEASURES: The incidence of acute respiratory illness
      was used to test the hypothesis that elderly persons taking care of children have
      the highest incidence, congregate-dwellers intermediate incidence, and those
      living independently the lowest incidence. RESULTS: The average incidence of
      acute respiratory illness was 2.5 per 100 person months, comparable to rates
      reported in the National Health Survey. The incidence of respiratory illness was
      significantly greater in subjects living in congregate settings or regularly
      caring for young children. Similarly, greater proportions of persons in the
      congregate and child-care groups reported at least one episode of illness (P <
      .05). A more detailed analysis of exposure shows that acute respiratory illness
      was significantly more common in subjects who had contact with children (P <
      .05). This risk was definitely present during the months November through
      February, and probably also during July through October, but was not observed for
      March through June. CONCLUSIONS: Elderly persons living in the community
      experience low rates of acute upper respiratory illness. Contact with children
      increases their risk of developing such illnesses during certain seasons of the
      year.

PMID- 7806736
TI  - Acute respiratory tract infection in daycare centers for older persons.
AB  - OBJECTIVE: To evaluate the rate of specific pathogens and clinical syndromes
      associated with acute respiratory tract infections (ARTI) in frail older persons
      attending daycare. DESIGN: Prospective descriptive study, without intervention.
      SETTING: Two sites of a senior daycare program providing all-inclusive care for
      the older persons in Rochester, New York. PARTICIPANTS: Staff members and
      participants of the day-care. MEASUREMENTS: Demographic, medical, and physical
      findings were collected from older subjects at baseline and while ill with
      respiratory illnesses. Nasopharyngeal specimens for viral and Chlamydia culture
      and sputum for bacterial culture were obtained from subjects when ill. Acute and
      convalescent sera were also collected with each illness and examined for viral,
      chlamydial, and mycoplasma infection. MAIN RESULTS: One hundred sixty-five
      illnesses were documented in 165 older daycare participants as well as 113
      illnesses among 67 staff members during the 15-month study. The rate of ARTI in
      the elderly group was 10.8 per 100 person months. The most common etiologies in
      both the staff and elderly participants were respiratory syncytial virus (RSV),
      Influenza A, and coronavirus. The etiologies of illnesses in the staff compared
      with those in elderly group were similar except that bacterial infections were
      significantly more common among the elderly (7% vs. 0, P = 0.05). Multiple
      pathogens were found to cocirculate within centers, and no clear outbreak of a
      predominant organism was noted. Cough and nasal congestion characterized most
      illnesses. The elderly experienced significantly more cough, dyspnea, and sputum
      production than did the staff. There were 10 hospitalizations related to
      respiratory infections and four deaths during the acute illness among the elderly
      group and none in staff.

PMID- 7806737
TI  - The Sessing scale for assessment of pressure ulcer healing.
AB  - OBJECTIVE: To describe a new observational scale, the Sessing scale, for
      measuring the progression of pressure ulcers. CRITERION STANDARDS: Changes in
      Shea stage and the diameter of healing pressure ulcers. SUBJECTS: A cohort of 84
      nursing home residents with pressure ulcers. RESULTS: There were strong
      relationships between changes in healing as measured by the Sessing Scale and
      those measured by the Shea Scale (Spearman's r = 0.90; P < .0001), and between
      changes in the Sessing scale compared with changes in ulcer diameter (Spearman's
      r = 0.64; P < .001). Test-retest reliability was good (Kappa = 0.84) in a sample
      of 50 subjects. CONCLUSION: The Sessing scale is a simple, easy to use,
      observational instrument with validity and reliability for the assessment of
      progression of pressure ulcers in a clinical or research setting. Findings
      indicate that the Sessing scale, with its description of granulation tissue,
      infection, drainage, necrosis, and eschar, measures an important domain of wound
      healing that is independent and perhaps as important to clinicians and
      researchers as either Shea stage or ulcer size.

PMID- 7806738
TI  - How do patients with Alzheimer's disease cope with their illness? A clinical
      experience report.

PMID- 7806739
TI  - Adverse reactions to controlled release levodopa/carbidopa in older persons: case
      reports.

PMID- 7806740
TI  - Functional status of geriatric rehabilitation patients: a one-year follow-up
      study.

PMID- 7806742
TI  - Improving quality of geriatric health care in four delivery sites: suggestions
      from practitioners and experts.

PMID- 7806741
TI  - Access to hospice programs in end-stage dementia: a national survey of hospice
      programs.
AB  - OBJECTIVE: Because care of end-stage dementia is a significant clinical problem
      for which alternative modes of care are needed, this study examined the extent to
      which hospice programs served dementia patients. DESIGN: A survey of 1694
      hospices with 1184 respondents (70%). PATIENTS: Identified patients had end-stage
      dementia, with no concurrent terminal illness. MEASURE: The proportion of end
      stage dementia patients in hospice was measured. RESULTS: Fewer than 1% of
      hospice patients had a primary diagnosis of end-stage dementia, and only 21% of
      the hospices served such patients. However, 7% of hospice patients had a dementia
      secondary to another terminal illness, and 56% of the hospices served such
      patients. For 80% of the hospices, the major problem in serving dementia patients
      was the difficulty in predicting their survival time. A higher proportion of for
      profit hospices served dementia patients (42%) compared with non-profit programs
      (22%) or public programs (15%), P < .001. CONCLUSIONS: A national survey of
      hospices revealed that few patients with primary dementia are currently treated
      by these programs, unless they have other terminal illnesses. An inability to
      predict survival was the major reason offered to explain this phenomenon. The
      higher percentage of patients with secondary dementia in hospice suggests that
      dementia per se does not make hospices care unfeasible. Similarly, the high
      proportion of for-profit hospices that enrolled patients whose dementia was
      primary implies the fiscal feasibility of providing hospice care for these
      patients. Further study is needed concerning the determinants of survival time in
      end-stage dementia.

PMID- 7806743
TI  - Diagnostic and prognostic value of ambulatory electrographic monitoring in older
      patients.
AB  - OBJECTIVE: To review the use of ambulatory electrocardiographic monitoring in
      detecting transient cardiac arrhythmias and myocardial ischemia in older patients
      and to determine the significance of these findings in predicting future cardiac
      events. DATA SOURCES: Reports on ambulatory electrocardiographic monitoring's
      capabilities in the detection and quantification of arrhythmias and myocardial
      ischemia were identified by multiple searches on the MEDLINE database and
      citations from relevant articles. STUDY SELECTION: Studies that demonstrated good
      research methodology were reviewed. Review was limited to studies that used reel
      to-reel or cassette recorders (not reel-time monitors). DATA EXTRACTION AND
      SYNTHESIS: Pertinent data were extracted from the studies, with specific emphasis
      on studies involving older patients. Prognostic findings were critically analyzed
      and compared between younger patients and older patients. Differences in
      prognoses younger patients with and without underlying heart disease were
      assessed. CONCLUSION: Ambulatory electrocardiographic monitoring is a noninvasive
      procedure that is beneficial in stratifying older patients with heart disease
      into high and low risk groups for future cardiac events. The presence of complex
      ventricular arrhythmias or silent myocardial ischemia as documented on 24-hour
      monitoring, especially in combination with left ventricular dysfunction or left
      ventricular hypertrophy, is highly predictive of future cardiac events, including
      sudden cardiac death and total cardiac mortality. The use of preoperative,
      intraoperative, and postoperative electrocardiographic monitoring may also be
      beneficial in stratifying older surgical patients into high and low risks for
      postoperative cardiac events.

PMID- 7806744
TI  - The changing epidemiology of human immunodeficiency virus infection in older
      persons.
AB  - OBJECTIVE: To describe the epidemiology of human immunodeficiency virus (HIV)
      infection diagnosed in persons aged 60 years and older at a large urban county
      hospital. DESIGN: Retrospective chart review of patients, aged 60 years and
      older, diagnosed with HIV infection, among 6,493 patients identified with
      positive EIA-HIV tests performed at Grady Memorial Hospital between January 1,
      1985 and July 1, 1992. RESULTS: A total of 32 HIV-infected elderly patients,
      including 27 men and five women, with a mean age of 64.8 years (range, 60-83
      years) were identified. Among the 27 men, HIV risk factors included:
      homosexual/bisexual (10 patients); injection drug users (IDU) (5); transfusion
      associated (2); heterosexual (2); eight patients had no HIV risk factor
      identified. Among the five women, only one had an identified risk factor (blood
      transfusion). HIV testing of 47% (15/32) elderly patients was performed after a
      diagnosis of an AIDS-defining opportunistic infection. Among 24 elderly patients
      who presented to a physician with signs or symptoms of HIV infection, testing for
      HIV was often delayed (median 3.1 months, range: 1-10 months). Eleven patients
      underwent work-ups to rule out a malignancy, and three patients were initially
      diagnosed with organic brain syndrome. Ten of the 32 patients (31%) had a history
      of syphilis, and 90% (19/21) of patients tested were found to be immune to
      hepatitis B. CONCLUSION: The majority of HIV-infected patients 60 years or older
      acquired their infection through sexual intercourse or IDU. The diagnosis of HIV
      infection in the elderly was usually not considered by clinicians until late in
      the course of infection, despite a high prevalence of prior sexually transmitted
      diseases (STDs). Our data indicate that clinicians who take care of elderly
      patients should do a complete sexual history and offer sexual education. HIV
      testing and counseling should be considered for all individuals with a history of
      recent STDs or reporting behaviors putting them at risk for HIV infection.

PMID- 7806745
TI  - Control of influenza outbreaks in the nursing home: guidelines for diagnosis and
      management.
AB  - A well coordinated plan that includes a mechanism for surveillance, rapid antigen
      detection testing and viral culture, infection control techniques and
      chemoprophylaxis is effective for aborting outbreaks of influenza A in the
      nursing home. Amantadine has been better studied in this situation, and
      experience with rimantadine is limited. The safety and efficacy of our dose
      guidelines for nursing home residents need to be studied and directly compared
      with rimantadine dose guidelines. Except for chemoprophylaxis, these guidelines
      can be applied to outbreaks of influenza B as well.

PMID- 7806746
TI  - Osteoporosis: emerging research strategies aim at bone biology, risk factors,
      interventions.

PMID- 7806747
TI  - Prevalence of depression in the aged: formal calculations versus clinical facts.

PMID- 7806748
TI  - Does human recombinant erythropoietin improve wound healing?

PMID- 7806749
TI  - Determination of causality.

PMID- 7806750
TI  - Weight loss and depression in a community nursing home.

PMID- 7806751
TI  - Causes of weight loss in a nursing home.

PMID- 7806752
TI  - Medicine and abortion.

PMID- 7806753
TI  - Induced abortion in the United States: a 1994 update.

PMID- 7806754
TI  - The bad old days are still here: abortion mortality in developing countries.
AB  - Each year, complications related to unsafe abortion account for at least one in
      seven maternal deaths worldwide. Nearly all of these deaths occur in developing
      countries and most are preventable. The authors argue that to prevent abortion
      related deaths, all women must have access to safe abortion and contraceptive
      services, and they discuss the strategies used to prevent abortion-related deaths
      -preventing unwanted pregnancy, preventing abortion, preventing unsafe abortion,
      and treating abortion complications. Some of these strategies have been
      effective, while others have failed. Preventing unwanted pregnancy is a very
      important starting point, but evidence suggests that it alone cannot solve the
      problems of abortion-related deaths. Efforts to prevent abortion, whether through
      legal or cultural sanctions, do not significantly reduce the number of abortions,
      and may even increase mortality. The technology to perform safe abortions is
      available, but remains underused. Finally, even under the best of circumstances,
      women will experience abortion complications (induced or spontaneous) and only
      through the prompt and effective treatment of these and other obstetric
      complications will deaths be averted.

PMID- 7806755
TI  - Abortion rights: legislative analysis.

PMID- 7806756
TI  - Abortion and health care reform.

PMID- 7806757
TI  - Physician-only and physician assistant statutes: a case of perceived but
      unfounded conflict.
AB  - In the 1970s, after the US Supreme Court declared in Roe v Wade that a woman has
      a fundamental right to terminate a pregnancy, most states enacted laws
      decriminalizing abortion. Generally, these statutes legalized abortion when
      performed by a physician. (Only six states--AZ, KS, NH, OR, VT, WV--do not
      require explicitly that abortions be performed by physicians.) At around the same
      time, but for different reasons, most states adopted regulatory measures
      establishing and defining the profession of physician assistant (PA). These laws
      broadly define the scope of practice of PAs as the practice of medicine by
      trained and licensed professionals under the supervision of physicians.
      Inconsistencies between physician-only abortion laws and PA statutes have
      generated confusion in the medical community as to whether PAs, working under the
      supervision of physicians, can legally perform abortions. Using three case
      studies, this article examines the statutory dynamic against the backdrop of the
      severe and intensifying shortage of trained abortion providers in the United
      States. The authors conclude that the perceived conflict between physician-only
      and PA statutes should not preclude PAs from providing this vital service.

PMID- 7806758
TI  - Abortion training in residency programs.
AB  - Following the expanded legalization of abortion in 1973, obstetrics/gynecology
      residency programs began to include training in these techniques. Due to a lack
      of specific requirements, however, many programs have never offered this
      training. Because most abortions are provided in freestanding clinics rather than
      in hospitals, many residents have not had an opportunity to learn abortion
      techniques. Since the 1970s, the number of residency programs that offer or
      require abortion training has decreased; currently, only about 12% of US
      obstetrics/gynecology residency programs require it. The development of
      collaborative programs where gynecology residents can go to learn abortion
      outside the hospital is one way to improve the proportion of residents who are
      trained. Training physicians from other specialties and midlevel clinicians is
      also being used to increase the number of abortion providers. New requirements
      specifying that obstetrics/gynecology training programs must include training in
      abortion techniques are under consideration. If adopted, these requirements may
      improve access to safe abortion for US women.

PMID- 7806759
TI  - Government in the examining room: restrictions on the provision of abortion.
AB  - Efforts to deter women from deciding to terminate their pregnancies take their
      toll on both women and health care providers. Unable to overturn Roe v Wade and
      ban abortion outright, opponents have sought to prevent women from obtaining
      abortions by imposing restrictions and burdening service providers. Among the
      most common measures adopted at the state level are mandatory delay, state
      scripted information, and parental notification requirements, while both federal
      and state policy makers have restricted Medicaid coverage for abortion. In its
      1992 decision in Planned Parenthood v Casey, the US Supreme Court made clear that
      states may not criminalize abortion prior to viability or allow anyone to veto a
      woman's decision to terminate her pregnancy. Nonetheless, the Court adopted a
      less protective "undue burden" standard for reviewing the constitutionality of
      restrictions on a woman's right to choose. In the wake of Casey, courts and
      legislative bodies continue to grapple with the extent to which the abortion
      choice is protected under federal and state constitutions. Meanwhile, women and
      health care providers are forced to endure the hardships caused by restrictive
      laws and policies.

PMID- 7806760
TI  - RU 486 beyond the controversy: implications for health care practice.
AB  - RU 486 has been mired in controversy since it was first synthesized in the 1980s.
      This paper assumes that RU 486 will eventually be available in the United States
      and examines how clinicians might integrate it into practice without compromising
      quality of care and patient safety. The mechanisms of action of RU 486, its
      prostaglandin augmentors, and other first-trimester abortifacients are briefly
      reviewed. Significant and often misunderstood issues are discussed, including the
      concern that women will fail to return for the second visit, in which they
      receive the prostaglandin; the need for back-up facilities; women's acceptance of
      RU 486 as an abortifacient; and its potential to increase abortion services to
      the underserved. The paper argues that RU 486 has implications for positive
      changes in the interpersonal dimensions of health care and discusses the
      adaptation in the organization of care that will have to take place in order to
      make RU 486 available to all women who might choose to use it.

PMID- 7806761
TI  - The unending struggle for legal abortion: conversations with Jane Hodgson.

PMID- 7806762
TI  - Postabortion medical care: management of delayed complications.

PMID- 7806763
TI  - Effects of centrally administered endothelin-3 on renal sympathetic nerve
      activity and renal blood flow in conscious rats.
AB  - Effects of intracerebroventricular (i.c.v.) administration of endothelin-3 (ET-3)
      on renal sympathetic nerve activity (RSNA) and renal blood flow (RBF), arterial
      blood pressure and heart rate were examined in conscious rats. Administration of
      ET-3 (1-50 pmol) through a chronically implanted cannula evoked an increase in
      arterial blood pressure and decreases in heart rate and RSNA, whereas RBF
      measured by Doppler flow probes did not change. Maximum changes in these
      responses occurred 10-15 min after i.c.v. administration of ET-3 and the
      responses returned to the control level after approximately 60 min. In sinoaortic
      denervated (SAD) rats, the decrease in RSNA induced by i.c.v. ET-3 was attenuated
      but still significantly persistent. During the experiments, we found that the
      injection of ET-3 (50-100 pmol) induced a barrel rotation, with an onset latency
      of 10-15 min. In those cases, prominent increases in arterial blood pressure and
      RSNA were observed, and these lasted for more than 60 min. The result shows that
      ET-3 can have centrally mediated effects on autonomic nerve activity as well as
      on cardiovascular function.

PMID- 7806764
TI  - Survival of the population of NADPH-diaphorase stained myenteric neurons in the
      small intestine of aged rats.
AB  - NADPH-diaphorase staining was performed on wholemount preparations of the
      muscularis externa (which includes the myenteric plexus) of the rat small
      intestine taken from animals of 4, 24 and 30 months of age. A population of NADPH
      diaphorase-stained neuron cell bodies was observed predominantly in the ganglia
      of the plexus. There were also many stained axons throughout the plexus and in
      the muscularis at all ages. The distribution of stained neurons around the
      circumference of the intestine was the same at all ages, being greater on the
      mesenteric than on the anti-mesenteric aspect. The numbers of NADPH-diaphorase
      positive neurons in the myenteric plexus were counted by a systematic random
      sampling method. At 4 months there were 3716 +/- 219 stained neurons per cm2.
      There was no difference in the neuron numbers between the 24- and 30-month
      animals but they were decreased in number by 15.01% in comparison to the 4-month
      rats when growth in the length of the intestine was taken into account. This
      reduction in neuron numbers is markedly less than that previously recorded for
      the total numbers of myenteric neurons in the aged rat small intestine suggesting
      that the NADPH-diaphorase neurons are relatively spared in old age. The density
      of NADPH-diaphorase-positive varicose axons in the myenteric plexus and in the
      muscularis appeared to be slightly greater in the aged animals. These results
      provide evidence that the majority of the population of the myenteric NADPH
      diaphorase-stained neurons, which may play a part in relaxation of the gut,
      survive in old age.

PMID- 7806765
TI  - Repeated renal and splenic sympathetic nerve stimulation in anaesthetized pigs:
      maintained overflow of neuropeptide Y in controls but not after reserpine.
AB  - The overflow and the arterial vascular effects of neuropeptide Y (NPY) in
      response to repeated sympathetic nerve stimulation of kidney and spleen were
      investigated in anaesthetized pigs. The responses under control conditions were
      compared to those evoked in pigs with tissue stores of noradrenaline (NA)
      selectively depleted by reserpine pretreatment combined with sympathetic nerve
      transection. The renal and splenic sympathetic nerves were repeatedly stimulated
      at 1 h intervals with one 5 Hz stimulation for 48 s and transmitter overflow
      determined. Between these stimulations, 5 min stimulations with bursts of 20 Hz
      (for 1 s every 10 s) were given in order to induce a depletion of nerve
      transmitter. In the control group, overflow of NPY and NA and vasoconstrictor
      responses were almost identical for the 5 consecutive stimulations in the kidney,
      whereas in the spleen the parameters showed a slight tendency to be reduced. In
      the reserpine-treated group, the initial evoked overflow of NPY was increased 8
      fold and 3-fold in the kidney and spleen, respectively, compared to the control
      group. Upon each subsequent stimulation the overflow decreased gradually, in
      parallel with the evoked vasoconstrictor response. After a 2 h recovery period no
      change in evoked overflow of NPY compared to the amount released by the previous
      stimulation was observed. The present study illustrates, the high capacity of
      maintenance of not only NA but also NPY overflow and vascular responses in
      control conditions, whereas the enhanced release of NPY in the absence of NA
      cannot be maintained. It is therefore possible that the NA-mediated prejunctional
      feedback mechanism is important for the maintenance of a constant NPY release in
      situations of high sympathetic activation.

PMID- 7806766
TI  - Distribution of extrinsic enkephalin-containing nerve fibers in the rat rectum
      and their origin in the major pelvic ganglion.
AB  - The distribution of nerve fibers containing enkephalin (ENK)-like
      immunoreactivity was examined in the rectum of aganglionosis rats (AGRs) which
      completely lack the intramural ganglion cells in the large intestine, and was
      compared with that of their normal littermates. Furthermore, Met5-enkephalin-Arg6
      Gly7-Leu8 (MEAGL)-like immunoreactive neurons projecting to the rectum were
      examined using retrograde tracing combined with immunohistochemistry in the major
      pelvic ganglion of normal male rats. In the intermuscular space of the
      aganglionic rectum of AGRs, unlike the pattern of the normal intermuscular
      plexus, moderate numbers of ENK-like-immunoreactive fibers were arranged in an
      irregular, coarse network; greatly diminished numbers of immunoreactive fibers
      were found in the submucosa. No ENK-like-immunoreactive fibers were seen in the
      circular muscle layer and mucosa. In the normal rat rectum, ENK-like
      immunoreactive fibers were seen throughout all layers, and immunoreactive nerve
      cells were found predominantly in the myenteric plexus of colchicine-treated
      animals. Fluoro-Gold injected into the upper rectum labelled numerous principal
      ganglion neurons in the major pelvic and inferior mesenteric ganglia. Less than
      10% of tracer-labelled neurons were positive for fluorescein immunolabelling of
      MEAGL in the major pelvic ganglion; no immunoreactive neurons were found in the
      inferior mesenteric ganglion. In the major pelvic ganglion of the colchicine
      treated normal rats, about 5% of principal ganglion neurons were immunoreactive
      for MEAGL. Comparison of serial paraffin sections of the major pelvic ganglion
      stained for tyrosine hydroxylase (TH), MEAGL and vasoactive intestinal
      polypeptide (VIP), respectively, revealed that more than half of MEAGL-like
      immunoreactive neurons were also positive for TH; there was no case showing co
      existence of MEAGL with VIP in the principal neurons. These results indicate that
      a small number of enkephalin-containing neurons in the major pelvic ganglion
      project to the rectum, and that more than half of these neurons are
      postganglionic sympathetic. They may terminate mainly in the myenteric ganglia in
      the rectum.

PMID- 7806767
TI  - Neural input regulates tissue NGF and growth of the adult rat urinary bladder.
AB  - To gain insight into the effect of innervation on neurotrophin production, NGF
      levels in the urinary bladder were measured following unilateral ganglionectomy
      (bladder denervation) or separation of the post-ganglionic bladder neurons from
      the central nervous system of the adult rat (bladder and ganglion
      decentralization). These interruptions of the neural input to half of the bladder
      caused histological evidence of smooth muscle growth, increased bladder weight
      (denervation-3 weeks: 98.6 +/- 6 mg; decentralization-3 weeks: 94.0 +/- 7 mg vs.
      control: 79.6 +/- 4 mg, P < 0.05), transient increases in tissue NGF up to 10
      fold (1.99 +/- 0.65 pg NGF/bladder control vs. 20.24 +/- 0.53 (P < 0.05)
      denervated, ipsilateral, 1 week) and hypertrophy of the neurons in the pelvic
      ganglia supplying the bladder (control: 340 +/- 4.4 microns2; denervated-3 weeks:
      530 +/- 6.8 microns2, P < 0.05; decentralized-3 weeks: 463 +/- 6.8 microns2, P <
      0.05). These data suggest that neural input has a significant role in regulating
      growth of the bladder. Furthermore, the findings show that innervation influences
      tissue levels of NGF in the bladder.

PMID- 7806768
TI  - Effects of microinjection of N-methyl-D-aspartic acid into the nucleus tractus
      solitarii on cerebral blood flow in anesthetized rats.
AB  - N-Methyl-D-aspartic acid (NMDA) (10 pmol in 100 nl of 0.9% sodium chloride
      solution) was microinjected into the nucleus tractus solitarii (NTS) of urethane
      anesthetized, paralyzed and artificially ventilated rats, and cerebral blood flow
      (CBF) was determined using a combination of labeled microspheres. Moderate
      hypertension within the upper limit of cerebral autoregulation was induced by
      blood transfusion in order to measure CBF at normotension. Arterial blood
      pressure (ABP) was decreased by unilateral microinjection into the NTS in these
      rats but remained within normotensive range. The CBF in the cerebral cortex
      ipsilateral to the stimulated NTS significantly (P < 0.01) decreased from 38 +/-
      4 (mean +/- S.E.M) to 27 +/- 4 ml.min-1.(100 g)-1(n = 9). The cerebrovascular
      resistance (CVR) in the cerebral cortex ipsilateral to the stimulated NTS
      significantly (P < 0.01) increased from 2.6 +/- 0.3 to 4.1 +/- 0.7 mmHg per
      [ml.min-1.(100 g)-1]. Blockade of NMDA receptors in the NTS with D,L-2-amino-5
      phosphonovalerate (AP5, 500 pmol) abolished the CBF decrease and CVR increase
      responses elicited by microinjection of NMDA into the NTS (n = 9). Blockade of
      non-NMDA receptors in the NTS with 6,7-dinitro-quinoxaline-2,3-dione (DNQX, 100
      pmol) had little effect on the CBF decrease and CVR increase responses elicited
      by microinjection of NMDA into the NTS (n = 10). Microinjection of the vehicle
      solution into the NTS had no effects on cerebral circulation (n = 7). Cerebral
      autoregulation was well maintained at moderate hypertension induced by blood
      transfusion and at normotension returned from moderate hypertension following
      controlled hemorrhage (n = 8). These results suggest that the NMDA receptors in
      the NTS may be involved in the control of cerebral circulation.

PMID- 7806769
TI  - Influence of humoral control peptides on medullary vasomotor control neurons:
      microstimulation and double-labeling studies using SHR and WKY rats.
AB  - To study the influence of humoral control peptides on medullary vasomotor control
      neurons, angiotensin II (AII), arginine vasopressin (AVP) and atrial natriuretic
      peptide (ANP) were microinjected into three vasomotor control areas, i.e., the
      area postrema (AP), the nucleus tractus solitarii (NTS) and the rostral
      ventrolateral medulla (RVLM), of spontaneously hypertensive rats (SHR) and
      normotensive Wistar Kyoto rats (WKY), and the evoked cardiovascular response was
      observed. Unlike the injection areas, the threshold dose of one peptide for the
      cardiovascular response was similar, but the threshold dose differed from peptide
      to peptide. The threshold dose was lower for AII (0.15-0.29 pmol), in-between for
      ANP (0.9-1.5 pmol) and higher for AVP (14-30 pmol). No significant difference in
      the threshold dose was observed between SHR and WKY, suggesting that hypertension
      in SHR may not be due to the abnormal sensitivity to the three peptides of the
      vasomotor control neurons in the AP, NTS, and RVLM. The structural basis of the
      results of the microstimulation experiment was supported by the double-labeling
      study. The NTS neurons were innervated by (1) the AII-immunoreactive (ir) neurons
      in both sides of the lateral hypothalamic area (LH), the RVLM and the caudal
      ventrolateral medulla, and (2) the ANP-ir neurons in both sides of the
      paraventricular nucleus (Pa) and the LH. The RVLM neurons were innervated by (1)
      the AII-ir neurons in both sides of the LH and ipsilateral side of the lateral
      parabrachial nucleus (Pbl) and (2) the ANP-ir neurons in the ipsilateral Pbl.
      There was no evidence that the AVP-ir neurons in the Pa and the supraoptic
      nucleus innervate the NTS and the RVLM neurons, or that the AII, ANP or AVP-ir
      neurons innervate the AP neurons. This study suggests that in common with SHR and
      WKY rats AII and ANP may influence both the NTS and RVLM not by the humoral
      pathway but by the neural pathway, and AVP may not influence the three vasomotor
      control areas by the neural pathway.

PMID- 7806770
TI  - Gastro-oesophageal afferent and serotonergic inputs to vagal efferent neurones.
AB  - Peripheral 5-HT3 receptor mechanisms are involved in activation of
      gastrointestinal (GI) mucosal vagal afferent fibres. 5-HT3 receptor mechanisms in
      the central nervous system (CNS) may be involved in behavioural and reflex
      motility responses. This study investigates the processing of different sensory
      inputs in the CNS and the involvement of 5-HT3 receptors at these different
      levels. In Urethane (1.5 g/kg, i.p.) anaesthetized, splanchnectomized ferrets,
      the jugular vein was cannulated for intravenous (i.v.) drug injection, and the
      coeliac axis for intraarterial (i.a.) injection close to the upper GI tract. The
      carotid artery was intubated with a T-cannula for CNS-directed intracarotid
      (i.c.) injections. An intragastric cannula was used for fluid distension (40-50
      ml), and an oesophageal catheter for balloon distension (2 ml). Efferent fibres
      were dissected from the right cervical vagus for single-unit recording. Nineteen
      single vagal efferent fibres were selected, with low frequency resting discharge
      (2.5 +/- 0.3 impulses/s), but no respiratory or cardiovascular phasic input. All
      responded rapidly (< 2.5 s) to gastric distension (532 +/- 230% change in firing
      rate) and oesophageal distension (300 +/- 170%). Gastric distension caused
      excitation in 14 fibres, inhibition in 4 fibres, and a biphasic response in 1.
      Oesophageal distension excited 16 and inhibited 3. Discharge was also influenced
      by i.a. injection of 5-HT or the 5-HT3 receptor agonist 2-methyl 5-HT (10-100
      micrograms) in all fibres tested. These responses consisted of rapid (< 2.5 s)
      and powerful changes in firing rate, with excitation, inhibition or biphasic
      responses. 65% of responses to i.c. or i.v. injection were opposite in direction
      to those after close i.a. injection, indicating the activation of a different
      population of receptors. No differences were seen between effects of i.c. and
      i.v. injections. The 5-HT3 receptor antagonist granisetron (100 micrograms/kg,
      i.v.) blocked or reduced efferent responses to 5-HT receptor agonists, whereas
      responses to gastric and oesophageal distension were unchanged. Thus there is
      extensive convergence of inputs from gastric and oesophageal mechanoreceptors
      onto vagal motorneurones. These central effects of mechanical stimuli do not
      involve 5-HT3 receptor mechanisms. Other 5-HT3 receptor inputs are evident,
      probably peripherally from GI mucosal afferent fibres and from within the CNS.

PMID- 7806771
TI  - Growth factors and the development and plasticity of the enteric nervous system.

PMID- 7806772
TI  - Effects of acrylamide on cotransmission in perivascular sympathetic and sensory
      nerves.
AB  - The effects of chronic administration of acrylamide on sympathetic and sensory
      nerves were examined in the mesenteric artery of rabbits. The noradrenaline (NA)
      content of the artery was significantly decreased and the total contractile
      response to electrical field stimulation (4-64 Hz) markedly reduced in the
      acrylamide group. This was not due to an impairment of the contractility of the
      smooth muscle or to alterations in the postjunctional receptors. At 16 Hz, only
      the purinergic component of sympathetic cotransmission was significantly reduced
      by acrylamide. At 64 Hz, both the purinergic and the adrenergic components were
      significantly decreased. Field stimulation of the artery pretreated with
      guanethidine and precontracted with NA produced a frequency-dependent relaxation
      which was prevented by capsaicin and thus mediated by perivascular sensory
      nerves. In contrast to its effects on sympathetic cotransmission, acrylamide
      resulted in a trend, although not significant, towards increased responses at
      each frequency studied (2-16 Hz). 2-Methylthio-ATP (2Me-S-ATP) caused
      significantly greater relaxation following acrylamide treatment while vasodilator
      responses to calcitonin gene-related peptide and substance P were unchanged. It
      is concluded that, in addition to its known action in producing neuropathy in
      myelinated somatic motor and sensory nerves, acrylamide causes damage to
      unmyelinated perivascular sympathetic fibres. Purinergic mechanisms may be
      particularly susceptible to acrylamide since both the purinergic component of
      sympathetic vasoconstriction and the relaxation in response to 2Me-S-ATP were
      affected by acrylamide treatment.

PMID- 7806773
TI  - Immunohistochemical studies on the intestinal nerve of Remak in the male chicken.
AB  - A peroxidase anti-peroxidase method was used to investigate and compare the
      distribution of neuropeptide and catecholamine synthesizing enzyme immunoreactive
      (IR) ganglion cells and nerve fibres in the intestinal nerve of Remak (INR) of
      male chickens. In the INR there were three kinds of ganglion cells: tyrosine
      hydroxylase (TH)-, aromatic L-amino acid decarboxylase (AADC)- and
      phenylethanolamine-N-methyltransferase (PNMT)-IR cells; AADC- and PNMT-IR but TH
      immunonegative cells; and ganglion cells being immunoreactive for methionine
      enkephalin (mENK)- and somatostatin (SOM). The first one was distributed
      throughout the INR. The second was restricted in the ileojejunal region, and the
      last was localized in the rectal region. Substance P- and vasoactive intestinal
      polypeptide-IR nerve fibres were distributed in common but variable in number
      around three kinds of ganglion cells. Then TH-IR cells were characterized by the
      distribution of many calcitonin gene related peptide- and a few cholecystokinin
      IR fibres. mENK and SOM-IR cells, and TH-immunonegative cells were distinguished
      by the distribution of SOM- and galanin-IR fibres. In addition, TH-immunonegative
      cells were characterized by the distribution of mENK- and neuropeptide Y-IR nerve
      fibres which were very few in number. Fig. 21 summarizes the connections
      described in the present study.

PMID- 7806774
TI  - Roles of noradrenaline and ATP in sympathetic vasoconstriction of the guinea-pig
      main ear artery.
AB  - This study has investigated the roles of noradrenaline (NA) and adenosine 5'
      triphosphate (ATP) in sympathetic vasoconstriction of the main ear artery from
      guinea-pigs. A range of agents which interact with adrenoceptors or purinoceptors
      was tested on contractions produced by exogenous NA or ATP, and on contractions
      produced by transmural stimulation of sympathetic axons. Contractions produced by
      NA were antagonized competitively by prazosin (Schild plot slope 0.88 +/- 0.13,
      not significantly different from 1.0). Dihydroergotamine (10 microM) produced
      significant depression of contractions produced by all concentrations of NA.
      Yohimbine (1 microM) caused a small rightward shift in the NA concentration
      response curves (0.34 log units), whereas propranolol had no effect. alpha,beta,m
      ATP (6 microM) enhanced contractions produced by low concentrations of NA (0.1-1
      microM), whereas suramin (30 microM) produced a slight depression in the maximum
      NA-induced contraction in all experiments. Contractions produced by ATP (0.1 mM)
      were greatly reduced by suramin (30 microM; 59% reduction) and by alpha,beta,m
      ATP (6 microM); 96% reduction), and were slightly depressed by dihydroergotamine
      (10 microM; 12% reduction). Transmural electrical stimulation with trains of 200
      300 pulses produced contractions which were rapid in onset and recovery, and
      sometimes were biphasic. Contractions at both 5 Hz and 20 Hz were reduced by 50
      70% after treatment with prazosin (0.1-1 microM). The remaining contractions were
      enhanced significantly by yohimbine (1 microM), were reduced very slightly by
      dihydroergotamine, and were largely abolished by guanethidine (1 microM).
      alpha,beta,m-ATP (1-100 microM) alone often enhanced neurogenic contractions (by
      100-200%), whereas suramin (30 microM) alone reduced contractions by
      48%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7806775
TI  - A fall in arterial blood pressure produced by inhibition of the caudalmost
      ventrolateral medulla: the caudal pressor area.
AB  - The caudal edge of the ventrolateral medulla was mapped to localize sites where
      microinjections of L-glutamate (L-glu) produce pressor responses in paralyzed and
      artificially ventilated urethane-anesthetized rats. Pressor responses ranging
      from 15 to 65 mmHg were obtained when L-Glu (0.25 M, 200 nl) was microinjected in
      the ventral medullary surface within an area localized between the rootlets of
      the XII and first cervical nerves, lateral to the pyramids and just medial to the
      spinal roots of the XI cranial nerve. This area has been called the caudal
      pressor area (CPA). Inhibition of the CPA by microinjection of GABA or glycine
      resulted in marked falls (15-45 mmHg) of arterial blood pressure (AP).
      Hypotension in response to CPA inhibition was also obtained in unanesthetized
      decerebrate animals. Cardiovascular responses to CPA stimulation or inhibition
      depend on the activity of neurons in the rostral ventrolateral medulla (RVLM).
      During hypotension provoked by RVLM inhibition, pressor responses to CPA
      stimulation were abolished. Conversely, pressor responses to RVLM stimulation
      were maintained during hypotension produced by inhibition of CPA. Pressor
      response to bilateral carotid occlusion were not reduced by CPA inhibition. We
      conclude that cells in the caudal most ventrolateral medulla exert a tonic
      pressor activity that contributes to maintenance of basal levels of the vasomotor
      tone and arterial blood pressure, its inhibition, however, does not prevent the
      pressor response to carotid occlusion.

PMID- 7806776
TI  - Projections from the prevertebral and major pelvic ganglia to the ileum and large
      intestine of the male rat.
AB  - The sympathetic innervation of the gut arises from the prevertebral and pelvic
      ganglia, and to a variable extent, from neurons located in the paravertebral
      ganglia, the splanchnic and intermesenteric nerves. In this study we have
      injected retrograde tracers into the wall of the ileum and several regions of the
      large intestine to determine the proportion of neurons supplying these regions
      from each of the ganglia and nerves. The sympathetic supply to the ileum arises
      primarily from neurons in the splanchnic nerves and the paravertebral ganglia T9
      T11 (SPL) and the coeliaco-mesenteric ganglion complex (CG/SMG), with a small
      supply from the proximal intermesenteric nerves (IMN). The distribution of
      neurons projecting to the proximal colon is very similar, although some labelled
      neurons are found throughout the length of the IMN and also in the inferior
      mesenteric ganglion (IMG). The middle colon is primarily supplied by the IMN and
      the IMG, although this region receives innervation from all the ganglia and
      nerves investigated, including the major pelvic ganglia (MPG). Neurons located in
      the distal two-thirds on the IMN and more caudal structures were labelled from
      the distal colon. The distal colon is the only region of gut to receive a
      relatively large innervation from the MPG, with approximately one third of
      labelled neurons in each of the IMN, IMG and the MPG. These studies also compared
      two retrograde tracers, Fast Blue and Fluorogold. Fluorogold was found
      specifically to label neurons projecting to each region of intestine injected.
      However, when injected into the middle colon, Fast Blue labelled neurons that
      project to this region as well as many neurons that Fluorogold studies indicate
      project to other regions; Fast Blue should therefore be used only with caution.

PMID- 7806777
TI  - Anal and rectal motility responses to distension of the urinary bladder in the
      cat.
AB  - The neural pathways and possible transmission mechanisms of the integrated
      autonomic nervous control of the urinary bladder and anorectum, were investigated
      in chloralose anaesthetized cats. Bladder distension and spontaneous detrusor
      contractions increased internal anal sphincter-tone, a response which was blocked
      by an alpha-adrenoceptor antagonist. Moreover, a nicotinic transmission step was
      present. Both the afferent and efferent limbs of the reflex were conveyed in the
      postganglionic hypogastric nerves and the preganglionic lumbar splanchnic nerves.
      Intact connection with the central nervous system was therefore essential.
      Contrasting to the specific reflex response in the internal anal sphincter,
      bladder distension also elicited a nociceptive vaso-pressor response. Rectal
      motility appeared to be unaffected by bladder distension.

PMID- 7806778
TI  - Measurement of human sympathetic nervous responses to stressors by
      microneurography.
AB  - Human sympathetic nervous responses have been extensively studied using various
      stressors; however, there have been few comparisons of the patterns of
      sympathetic nervous activation which may be produced by different stressors. The
      purpose of this study was to explore whether different stressors produce
      differing degrees of sympathetic activation in muscle vasoconstrictor nerve
      fibres.

PMID- 7806780
TI  - Recent advances in pediatric epilepsy: 2. Management of difficult seizure
      problems.

PMID- 7806779
TI  - Pharmacology and therapeutic aspects of antiepileptic drugs in pediatrics.
AB  - In the past year, several new antiepileptic drugs have emerged that have
      potential benefits for children with epilepsy. The spectrum of adverse effects is
      the principal feature that differentiates among the older drugs used to treat
      partial and related seizures, including simple partial, complex partial, and
      partial secondarily generalized seizures. Based on studies in adults with
      refractory seizures, the new or investigational compounds felbamate, gabapentin,
      lamotrigine, and vigabatrin should be active against these types of seizures in
      children, but none of them have been subjected to pediatric randomized controlled
      trials, and no studies have been done that compare new and old drugs in this
      category. Thus, the new drugs hold promise in children with these types of
      seizures, but their role relative to old drugs has not been elucidated. Several
      of the new drugs are active against myoclonic and generalized tonic-clonic
      seizures, but thus far, none have been proven to possess antiabsence activity in
      children. Open-label investigations suggest that lamotrigine may be helpful in
      Lennox-Gastaut syndrome, and vigabatrin in infantile spasms. Only felbamate has
      been evaluated in a randomized controlled study in children, in which it has
      proven beneficial against astatic and generalized tonic-clonic seizures in
      children with Lennox-Gastaut syndrome. Whereas investigations of these and other
      novel drugs are ongoing, this is an active and exciting period in pediatric
      antiepileptic drug development.

PMID- 7806781
TI  - Syndromic classification in the management of childhood epilepsy.
AB  - Epilepsy syndromes, defined as clusters of symptoms or signs occurring
      consistently together, form the basis of the currently accepted classification of
      the epilepsies. The concept of epilepsy syndrome is practical for the diagnosis,
      prognosis, orientation of treatment, and selection of appropriate investigations,
      but it is of variable specificity and usually does not give information on causes
      and mechanisms of an epilepsy. Some syndromes, such as childhood absences,
      partial epilepsy with centrotemporal spikes, or juvenile myoclonic epilepsy, are
      precisely characterized while other syndromes such as grand mal on awakening or
      the multiple syndromes with myoclonic seizures are poorly delineated. The
      usefulness of the concept is limited to well-defined and generally accepted
      syndromes and many cases of epilepsy do not fit easily in recognizable syndromes.

PMID- 7806782
TI  - The contributions of epidemiology to the understanding of childhood seizures and
      epilepsy.
AB  - Up through the 1960s, studies of epilepsy were based on patients seen in tertiary
      referral centers, many of whom had refractory epilepsy. Based on these early
      studies, epilepsy was believed to be a chronic, progressive, and incurable
      disorder. Seizures were thought to cause damage and result in further seizures.
      Clinical management of children with seizures reflected these beliefs. Over the
      last 25 to 30 years, epidemiologic studies have demonstrated that, contrary to
      these earlier beliefs, the prognosis of most childhood seizures and epilepsy is
      excellent. Prognosis is largely determined by the underlying etiology and not the
      seizures themselves. The differences in the assessment of the prognosis of
      seizures derived from the earlier studies versus the later epidemiologic studies
      are largely due to several biases that occurred in the earlier studies. These
      biases are explained. Several examples are provided of how the epidemiologic
      studies have greatly altered the prevailing views regarding the prognosis of
      seizures, and, by doing so, the management of seizures.

PMID- 7806783
TI  - Status epilepticus in children: update and review.
AB  - This report presents a brief description and classification of status
      epilepticus. This neurologic emergency occurs more frequently in young children
      and elderly adults, although patients of all ages may experience prolonged
      seizures. The pathophysiology and prognosis of the disorder are presented, as
      well as a review of drugs commonly used for the treatment of convulsive status
      epilepticus. The morbidity and mortality of status epilepticus are significant
      and directly dependent upon prompt and appropriate medical therapy. Advances in
      understanding various aspects of status epilepticus may lead to improved outcome
      for affected patients.

PMID- 7806784
TI  - Early surgery for epilepsy: redefining candidacy.
AB  - Surgical resection for localization-related epilepsy has recently become a
      generally accepted treatment in children. Evidence of the poor outcome in natural
      history studies of temporal lobe epilepsy in childhood initiated consideration of
      surgical intervention. Subsequent favorable outcome following surgery was
      encouraging. A number of variables differentiate adults with focal seizures from
      children. Evolving biologic factors modify the clinical and
      electroencephalographic expression of seizures in childhood. The pathologic
      substrate is different, and there is a higher incidence of extratemporal
      epilepsy. Chronic seizures beginning under age 2 years rarely remit, especially
      when associated with a demonstrable structural lesion. Behavioral consequences of
      chronic seizures are significant and become a major problem by adolescence if
      seizures are not controlled. Early surgery results in superior functional
      outcome, although subtle deficits persist postoperatively. Surgical outcome is as
      favorable as in adults with improvements in behavioral status and socialization.
      Abundant data exist to more adequately assess the benefits and risks of surgery
      in children so that intervention is not deferred longer than it needs to be.

PMID- 7806785
TI  - Neurobiologic considerations in early surgery for epilepsy.
AB  - Children with well-localized medically resistant seizures are often referred for
      surgical therapy. In young children, at least three maturational issues play a
      significant role in the selection process and long-term outcome. First, the early
      years are a time of exceptionally rapid brain development leading to dynamic
      changes in the electroencephalogram and the clinical expression of seizures. Many
      early-onset seizure presentations are also associated with catastrophic outcomes,
      developmental arrest, or regression. Second, the immature limbic system may be
      vulnerable to stresses operating in early life, although the consequences may not
      become apparent for many years. Third, in comparison to the adult, the child's
      nervous system typically exhibits superior functional recovery after lesioning,
      but the process of sparing and recovery is often incomplete. An understanding of
      how these neurobiologic factors influence developmental outcome will ultimately
      lead to greater selectivity of candidates for early surgery and to improved long
      term prognosis.

PMID- 7806786
TI  - Commissurotomies in children.
AB  - Although corpus callosotomy has been used since 1940 to treat severe, medically
      intractable seizure disorders, controversy remains as to when, or even if, the
      surgery should be performed. Unlike other types of surgical therapy of epilepsy
      where the epileptic focus is identified and removed, corpus callosotomy is used
      to interrupt the propagation of epileptic discharges. The procedure is primarily
      used in patients with secondarily generalized seizures in whom focal resections
      are not possible. Long-term follow-up studies of post-callosotomy patients are
      few and flawed by lack of accurate seizure counts and quality-of-life measures.
      Although it remains difficult to predict those patients who will benefit from the
      surgery, it appears that patients with "drop" attacks benefit the most from the
      procedure.

PMID- 7806787
TI  - Subdural monitoring in the evaluation of children for epilepsy surgery.
AB  - Noninvasive assessment of children with chronic epilepsy is often imprecise and
      localization of seizure foci requires intracranial electroencephalographic
      monitoring. Subdural electrodes provide coverage of large areas of neocortex and
      are ideally suited for evaluating children with intractable epilepsy and to
      functionally map critical cortex. This report discusses the role of subdural
      electroencephalography in the evaluation of childhood epilepsy.

PMID- 7806788
TI  - A review of cognitive outcome after unilateral lesions sustained during
      childhood.
AB  - Views on human brain organization early in development have swung back and forth
      between the extreme notions of complete equipotentiality and adult-like
      specialization. Recent research on the cognitive effects of early brain damage
      supports an intermediate position and suggests that many claims on the older
      literature must be re-examined in the light of new evidence that cognitive
      impairments are sometimes attributable to previously ignored factors, such as a
      history of seizures, time since injury, and unsuspected lesions that are now
      detectable with neuroimaging techniques.

PMID- 7806789
TI  - Future directions in pediatric epileptology.
AB  - Rapid developments in several areas of epileptology alter or clarify concepts and
      bring new hope to epileptic patients and their associates. Brief discussions of
      such advances comprise this report. Experimental and clinical data concerning the
      pathogenesis of cognitive impairment in some epileptic conditions are reviewed.
      Epidemiologic studies have altered some long-held concepts concerning etiology of
      seizures in early life. Molecular genetic studies have disclosed abnormalities in
      some of the epilepsies: a genetic predisposition to epilepsy may explain why some
      patients with cortical lesions develop seizures and others do not. It is
      suggested that many questions regarding surgery in pediatric epilepsy will be
      resolved only by more reliable techniques of case selection and follow-up.
      Practitioners in developed countries must realize how rudimentary is the care
      given to the unfortunate many with seizure disorders in less advantaged areas.

PMID- 7806790
TI  - Children with seizures: when can treatment be deferred?
AB  - The decision whether or not to recommend chronic antiepileptic drug treatment for
      a child with seizures requires a risk-benefit analysis tailored to each
      individual case. Because all of the available antiepileptic medications have some
      potential adverse effects, the analysis may weigh in favor of a decision not to
      treat. Three clinical scenarios in pediatrics in which the no-treatment option
      may often be appropriate include a single unprovoked seizure, febrile seizures,
      and benign focal epilepsy of childhood.

PMID- 7806791
TI  - Computed tomography scanning with image reconstruction in evaluation of distal
      radius fractures.
AB  - Seventeen patients with 18 intraarticular distal radius fractures underwent
      computed tomography (CT) scanning and image reconstruction to evaluate their
      distal radius fractures. All patients were selected prospectively because of
      intraarticular extension and/or displacement of their fractures on pre- or post
      reduction plain films. Patients who were not surgical candidates for open
      reduction and internal fixation of their fracture were not included in the study.
      X-ray films and CT scans were viewed separately and in random order by a senior
      radiologist not familiar with the cases. Both x-ray films and CT scans readily
      showed extension of fracture lines into the radiocarpal joint, radial shaft, and
      the ulnar styloid, but CT scans were better than x-ray films at demonstrating
      fracture involvement of the distal radioulnar joint, the extent of articular
      surface depression, and the amount of comminution. Due to the cost, it is
      recommended that the test only be used for patients who are surgical candidates
      for open reduction and internal fixation or when more information about the
      extent of comminution and joint depression is required.

PMID- 7806792
TI  - Simultaneous proximal row carpectomy and radius to distal carpal row arthrodesis.
AB  - We assessed the functional results of simultaneous proximal carpal carpectomy and
      radius to distal carpal row arthrodesis. A retrospective review of patients
      undergoing wrist arthrodesis for degenerative joint disease was performed.
      Patients with rheumatoid arthritis or spastic hemiplegia were excluded.
      Simultaneous proximal row carpectomy and radius to distal carpal row arthrodesis
      was performed in 38 patients using AO plates and 3.5 mm diameter screws. The mean
      follow-up time was 16 months, the fusion rate was 100%, and the average grip
      strength was 24 kg force or 79% of the contralateral hand measured at 10 degrees
      wrist extension. Patients with three or more screws placed in the metacarpal had
      significantly more plate-related complications and a higher rate of plate removal
      than those with two screws distally. Simultaneous proximal row carpectomy and
      radius to distal carpal row arthrodesis did not decrease the postoperative grip
      strength.

PMID- 7806793
TI  - Wrist arthrodesis: a combined intramedullary pin and autogenous iliac crest bone
      graft technique.
AB  - Forty-six wrist arthrodeses in 36 patients were reviewed. The technique used
      provided a reliable fusion method for a variety of wrist disorders. The
      arthrodeses were performed using an autogenous iliac crest bone graft, with an
      intramedullary Steinman pin placed within the distal radial and third metacarpal
      shafts, and an obliquely-placed Kirschner wire across the second metacarpal base
      into the radius. The distal ulna, instead of the radius, was used in patients
      with radial agenesis. Three patient populations were identified: group 1,
      connective tissue wrist disorders; group 2, congenital wrist disorders; and group
      3, acquired wrist disorders. A residual flexion, radial deviation deformity was
      noted with the congenital disorders. All patients had low demand requirements for
      this fused wrists. The average time of fusion for each group as 14, 15, and 12
      weeks, respectively.

PMID- 7806794
TI  - Scapholunate advanced collapse wrist salvage.
AB  - Patients with scapholunate advanced collapse (SLAC) wrist do not have to undergo
      total wrist arthrodesis; the SLAC pattern spares the radiolunate articulation,
      providing a basis for salvage. We report the results of 100 cases in which a
      technique comprised of scaphoid excision and limited wrist arthrodesis was used.
      The average followup period of 44 months revealed excellent functional status and
      a high rate of patient satisfaction. The majority of employed patients were able
      to return to their original jobs, and many chose to resume wrist-related
      recreational activities. Pain relief was good to excellent in most cases.
      Extension/flexion averaged 72 degrees (53% of a normal opposite wrist),
      radioulnar deviation 37 degrees (59%), and grip strength 80% of the opposite
      side. X-ray films revealed only two instances of radiolunate destruction, both in
      conjunction with ulnar translation of the carpus. The other 98 patients
      demonstrated a well-preserved radiolunate joint regardless of followup interval.
      Complications were few. Nonunion occurred in three cases. A dorsal impingement of
      the capitate and radius (12%) was felt to be technique-related and avoidable by
      careful capitolunate alignment.

PMID- 7806795
TI  - Surgical treatment of scapholunate advanced collapse.
AB  - This study reports the outcomes of six different reconstructive procedures for
      stage II and stage III scapholunate advanced collapse (SLAC) wrist in 55 cases
      followed an average of 50 months. Scaphoid excision and intercarpal arthrodesis
      was performed in 31 cases: four-corner arthrodesis in 23 cases and capitolunate
      arthrodesis in 8 cases. Proximal row carpectomy was performed in 12 cases,
      radioscapholunate arthrodesis in 5 cases, radioscaphoid arthrodesis in 3 cases,
      and primary total wrist arthrodesis in 4 cases. Following surgical treatment the
      majority of patients in all groups had less wrist pain. The nonunion rate was
      four cases for the capitolunate arthrodesis group compared with two for the four
      corner arthrodesis group. Six of 51 motion-sparing cases were converted to total
      arthrodeses. Scaphoid excision and four-corner arthrodesis reliably diminished
      wrist pain in patients with stage III SLAC wrist while maintaining a 54 degrees
      flexion-extension arc. Stage II SLAC wrist can be successfully treated with this
      procedure, radioscaphoid arthrodesis, or proximal row carpectomy. Of the three
      procedures, proximal row carpectomy best preserves wrist mobility, with a flexion
      extension arc of 71 degrees.

PMID- 7806796
TI  - Acute open reduction of a displaced scaphoid fracture in a child.

PMID- 7806797
TI  - Mechanical evaluation of the scaphoid shift test.
AB  - Manipulative examination of the carpal bones is an important facet of the
      examination of the wrist. Abnormal translation of portions of the carpus in
      response to applied force is a commonly used clinical indicator of ligament
      injury. Unilateral scaphoid hypermobility during the so-called scaphoid shift
      test is felt to represent traumatic instability, especially in the context of
      wrist injury. The test, however, is subjective, and requires considerable
      experience to correlate the degree of scaphoid mobility with pathologic
      significance. We used an instrument that quantifies the load-displacement
      behavior of the scaphoid and its supporting ligaments during application of a
      dorsally directed load at the scaphoid tubercle. We evaluated 18 uninjured
      (normal) wrists with clinical ligament examination and with mechanical testing.
      Subjects who exhibited a positive scaphoid shift had significantly increased
      displacement and significantly decreased stiffness when compared with subjects
      who did not have a shift.

PMID- 7806798
TI  - An in vitro model of fibroblast activity and adhesion formation during flexor
      tendon healing.
AB  - We studied fibroblast activity during tendon healing with an in vitro tendon
      culture model. Tendons were embedded in a translucent collagen gel matrix whose
      porous nature permitted free nutrient diffusion, fibroblast migration out of the
      tendon, and microphotographic documentation of fibroblast activity. Experiments
      were performed using one or more tendons cultured in the same collagen gel. We
      identified three zones of fibroblast activity in the gel. Zone I was an area of
      randomly dispersed cells directly adjacent to the tendon where collagen synthesis
      and remodeling were probably taking place. In zone II, spindle-shaped fibroblasts
      were aligned pointing away from the cut tendon end forming a sunburst-like
      aggregate of cells. Zone II fibroblasts were responsible for formation of
      migration trails by exerting a mechanical force on the collagen matrix, which was
      evident as a local gel contraction. Zone III was the leading edge of the sunburst
      populated by the fastest moving fibroblasts, which responded to guidance by other
      cut tendon ends. We speculate that the collagen gel used in the culture system
      may help maintain a chemotactic concentration gradient that allows fibroblasts to
      locate other distal cut tendon surfaces also embedded in the collagen gel.

PMID- 7806799
TI  - Comparison of a suture technique with the modified Kessler method: resistance to
      gap formation.
AB  - We performed an in vitro study using canine flexor tendons to compare the tensile
      properties of a suture technique for flexor tendon repair with the standard
      modified Kessler technique. The technique employs a central wire loop that
      connects the two transverse limbs of the modified Kessler suture. Both techniques
      were studied with and without a Lembert epitendinous stitch. The technique
      combined with an epitendinous suture provided the strongest resistance to gap
      formation, and its load at gap initiation was 100% greater than the load in
      tendons repaired with the modified Kessler and an epitendinous suture. Because of
      its increased resistance to gap formation, this suture technique may provide a
      safer margin for controlled early active motion after flexor tendon repair.

PMID- 7806800
TI  - Closed traumatic rupture of finger flexor pulleys.
AB  - Nine patients are described with closed traumatic rupture of the digital flexor
      pulley system. All presented with significant flexion contractures of the
      proximal interphalangeal joint and bow-stringing of the flexor tendons. In seven
      patients, the pathology was verified at surgery and pulley reconstruction
      provided a good result. The diagnoses in the other patients, treated
      conservatively, were verified by tenogram and magnetic resonance imaging.

PMID- 7806801
TI  - Fibroma of tendon sheath in the hand.
AB  - Seven cases of fibroma of tendon sheath in the hand are reviewed. These tumors
      are common enough to be considered in the differential diagnosis of a soft tissue
      tumor in the hand, as they comprised 7 of our series of 208 soft tissue hand
      tumors excised over a 15-year period. A marginal excision was performed in each
      case, and no tumor recurred after a mean follow-up interval of 8 years. The
      fibromas were adherent to tendons, tendon sheaths, and neurovascular structures,
      and thus were more difficult to excise without morbidity than other soft tissue
      hand tumors.

PMID- 7806802
TI  - Synovial chondromatosis of the proximal interphalangeal joint of a finger.

PMID- 7806803
TI  - Locking wrist with synovial chondromatosis: report of two cases.

PMID- 7806804
TI  - Aneurysmal bone cyst involving the long finger metacarpal in a child: a case
      report.

PMID- 7806805
TI  - Adenoid cystic carcinoma metastatic to the fingers: a case report.

PMID- 7806806
TI  - Metastatic transitional cell carcinoma to the hand.

PMID- 7806807
TI  - Uremic tumoral calcinosis: acute hand presentations mimicking infection.
AB  - Tumoral calcinosis is an uncommon condition of the hand characterized by
      deposition of calcium salts in the soft tissues of the extremities. The condition
      may be hereditary or acquired. Acquired tumoral calcinosis, also called tumoral
      calcification, is a rare manifestation of renal osteodystrophy due to derangement
      in divalent ion metabolism. Two chronic dialysis patients with tumoral
      calcification of the hand are presented. These cases are unusual in their rapid
      onset of presentation, mimicking acute infection. Prompt recognition of the
      condition may allow early nonsurgical intervention to preserve function.

PMID- 7806808
TI  - Cryptococcus infection of the hand.

PMID- 7806809
TI  - Septic arthritis in a normal interphalangeal joint following a dental procedure.

PMID- 7806810
TI  - Provocative testing for cubital tunnel syndrome.
AB  - This prospective study evaluated the clinical usefulness of provocative testing
      in 32 subjects with electrodiagnostically proven cubital tunnel syndrome and 33
      control subjects. Four provocative tests were included: Tinel's sign, elbow
      flexion, pressure provocation, and combined elbow flexion and pressure
      provocation. The mean age of the control group was 41 years and 46 years for the
      group with cubital tunnel syndrome. In the control group, provocative tests were
      rarely positive. In 44 extremities with cubital tunnel syndrome, 31 had a Tinel's
      sign, 33 had a positive elbow flexion test, 39 had symptoms with pressure only,
      and 41 had symptoms with a combination of pressure provocation and elbow flexion
      testing. The sensitivity of the Tinel sign was 0.70, and at 30 seconds, the
      sensitivities of the other provocative tests were: elbow flexion (0.32), pressure
      provocation (0.55), and pressure-flexion test (0.91). The most sensitive
      provocative test in the diagnosis of cubital tunnel syndrome was elbow flexion
      when combined with pressure on the ulnar nerve.

PMID- 7806812
TI  - Ganglion-related compression neuropathy of the palmar cutaneous branch of the
      median nerve: a report of two cases.

PMID- 7806811
TI  - Morphologic changes following endoscopic and two-portal subcutaneous carpal
      tunnel release.
AB  - This study describes the morphologic changes that occur following single incision
      endoscopic and two-portal subcutaneous carpal tunnel release. Seventeen patients
      were studied preoperatively and an average of 24 weeks postoperatively. Canal
      volume, carpal arch width, and median nerve palmar displacement and cross
      sectional area were measured by use of multiplanar reformation and three
      dimensional reconstruction of magnetic resonance images. Both methods produced a
      marked increase in canal volume and median nerve cross-sectional area; neither
      resulted in a significant change in carpal arch width. These data provide a
      morphologic basis for the belief that endoscopic or subcutaneous carpal tunnel
      release will produce clinical relief equivalent to open carpal tunnel release.

PMID- 7806813
TI  - Intercostal nerve transfer for brachial plexopathy.
AB  - Thirteen patients with traumatic brachial plexopathy underwent intercostal nerve
      transfer to the biceps motor branch (9 patients) or combined gracilis muscle and
      intercostal nerve transfer (4 patients; 3 for elbow flexion and 1 for elbow
      extension). Follow-up time ranged from 12 to 48 months (mean, 25 months) on 12
      patients. Useful elbow flexion or extension was obtained in a total of 9
      patients. Comparison of pre- and postoperative spirometry in 4 patients
      demonstrated a mild decline in pulmonary function, although there was no
      subjective change in respiratory status. Intercostal nerve transfer and combined
      gracilis muscle and intercostal nerve transfer are viable, although technically
      demanding, alternatives for restoring active elbow motion in patients with
      irreparable brachial plexus lesions when conventional tendon transfers are not
      feasible. The morbidity of intercostal nerve harvest with respect to pulmonary
      function is minimal.

PMID- 7806814
TI  - Functional outcome following traumatic upper limb amputation and prosthetic limb
      fitting.
AB  - Nineteen consecutive patients underwent traumatic upper limb amputation for
      nonreconstructible or replantible upper limb injury at a Level I trauma center
      over a 9-year-period. Eleven amputations were at the transradial level, five were
      transhumeral, and three were shoulder disarticulation. Eighteen patients
      underwent prosthetic limb fitting. Fifteen of the 18 initially underwent
      preparatory prosthetic limb fitting within 30 days following amputation with a
      body-powered, cable-driven prosthesis. Seventeen of the 18 achieved sufficient
      proficiency with their prostheses to allow them to return to work. Of these, 15
      maintained daily functional prosthetic use of at least 8 hours daily at a
      followup examination of 12 to 110 months. Use of prosthetic limb following
      traumatic upper limb amputation carries a high probability for functional
      rehabilitation if limb fitting and prosthetic training are instituted as soon as
      the residual limb can tolerate the prosthetic socket as opposed to waiting for
      the residual limb to "mature".

PMID- 7806815
TI  - Central slip attenuation in Dupuytren's contracture: a cause of persistent
      flexion of the proximal interphalangeal joint.
AB  - This paper stresses the importance of central slip attenuation in the management
      of Dupuytren's contracture. Such attenuation occurs in patients who have had
      prolonged proximal interphalangeal joint contractures and is a common problem
      when the flexion contracture exceeds 60 degrees. The diagnosis can be made at the
      time of surgical correction by a tenodesis test. If central slip attenuation is
      confirmed, the postoperative regime described here will give a better correction
      of what at first might appear to be an intractable proximal interphalangeal joint
      flexion deformity.

PMID- 7806816
TI  - Index finger extension and strength after extensor indicis proprius transfer.
AB  - We reviewed the long-term morbidity of the donor index finger following extensor
      indicis proprius tendon transfer in 34 patients with an average follow-up period
      of 8 years. An extension lag of the donor index was found to present in 24
      patients. In all patients a reduced extension strength of the donor index finger
      was noticed, either measured dependently (with concurrent long finger extension)
      or independently (without long finger extension). Despite these findings, 30 of
      the patients described no limitations in their daily life activities. In nearly
      all patients the dependent extension strength was superior to the independent
      extension strength. To prevent an extension lag, the surgeon should avoid
      surgical trauma to the dorsal aponeurosis ("hood") by sectioning the index tendon
      proximal to the hood.

PMID- 7806817
TI  - Mallet finger: results of early versus delayed closed treatment.
AB  - The efficacy of continuous splinting was retrospectively compared in two
      populations of 40 patients with soft tissue and bony mallet finger whose
      treatment was initiated within 2 weeks after injury (early) or more than 4 weeks
      after trauma (delayed). Splint treatment was successful in restoring active
      extension (with no more than 10 degrees extensor lag) in 17 of 21 patients in the
      early group and 15 of 19 patients in the delayed group. Neither the presence or
      absence of dorsal lip fracture less than one third of the articular surface of
      the distal phalanx nor the type of splint used affected the final outcome.
      Splinting was as effective in the delayed treatment population as it was in the
      early treatment population.

PMID- 7806818
TI  - The Mitek bone anchor: application to the hand, wrist and elbow.
AB  - Mitek (Norwood, MA) bone anchors were used to attach soft tissue to the bones of
      the hand, wrist, and elbow in 66 procedures (166 anchors). The technical
      difficulties, initial fixation, long-term stability, and postoperative
      complications were retrospectively reviewed. The technique was easy to learn and
      to use. Intraoperatively, secure fixation of soft tissue to bone was accomplished
      in every case, and follow-up x-ray films showed that 65 of the implants remained
      securely anchored in bone. The far cortex was penetrated six times, resulting in
      two complications. The Mitek bone anchor is an excellent technique for achieving
      soft-tissue fixation in the hand and upper extremity, but penetration of the far
      cortex should be avoided.

PMID- 7806819
TI  - Clinical application of the forearm tourniquet.
AB  - We undertook this prospective study of 148 consecutive hand and wrist procedures
      to evaluate the safety and efficacy of the forearm tourniquet. Patients were
      assigned to three groups based on tourniquet pressure used, ranging from 50 to
      125 mmHg above systolic blood pressure. The forearm tourniquet was well tolerated
      by all patients. No patient had neurologic complications. Minimal intraoperative
      bleeding occurred when the pressure was greater than 75 mmHg above systolic blood
      pressure. The forearm tourniquet is a safe and effective means of providing a
      bloodless field for wrist and hand surgery.

PMID- 7806820
TI  - Use of the double-layered free temporal fascia flap for upper extremity coverage.
AB  - Two layers of fascia exist in the temporal region, the temporoparietal fascia and
      the deep temporal fascia. Both can be elevated on a single vascular pedicle based
      on the superficial temporal artery, the double-layered temporal fascia flap. In
      our study, six patients who underwent upper limb coverage using the double
      layered temporal fascia flap are reviewed, and the versatility of this thin flap
      is discussed.

PMID- 7806821
TI  - Comments inspired by two letters on ulnar shortening osteotomy for ulnar
      impaction syndrome.

PMID- 7806822
TI  - Clinical commentary: pathogenesis of cumulative trauma disorder.

PMID- 7806823
TI  - "High five" hamate fracture.

PMID- 7806824
TI  - Reflex sympathetic dystrophy.

PMID- 7806825
TI  - Duodenal gastrinoma: the solution to the pancreatic paradox.
AB  - There has been a recent focus of attention on the duodenum as a major source of
      gastrinomas. The question has often arisen as to why the pancreas should give
      rise to gastrinomas because, in the adult, it contains no gastrin-producing (G)
      cells. However, the numerous G cells of the duodenum may proliferate and function
      as a "carcinoid" lesion, producing a relatively indolent tumor, much like a
      papillary carcinoma of the thyroid. On the contrary, islet cells of the pancreas,
      which do not produce gastrin, may behave much like a neuroendocrine carcinoma and
      may be defined as a "pancreatic gastrinoma" because they produce an ectopic
      hormone (gastrin). These lesions are capable of behaving much more aggressively,
      as do many other ectopic hormone-producing neoplasms. The recognition of the
      difference between these two types of gastrinoma is of considerable clinical and
      biological significance.

PMID- 7806826
TI  - Hospital care of acute nonvariceal upper gastrointestinal bleeding: 1991 versus
      1981.
AB  - Developments important to the care of upper gastrointestinal (UGI) bleeding
      occurred in the 1980s. We compared the features, care, and outcome of patients
      hospitalized with acute nonvariceal UGI bleeding in 1991 (n = 216) and 1981 (n =
      105). Most patient characteristics and the hemoglobin values were similar. Final
      diagnoses differed, mainly because there were more peptic ulcers and fewer
      unknown diagnoses in 1991. More patients had endoscopy in 1991 (94%); 92% of
      endoscoped patients had the procedure within 24 h of admission. The hospital stay
      of patients without surgery or comorbidity in 1991 was 2.8 +/- 0.1 days,
      significantly shorter than that in 1981. In 1991 only one half of patients
      received blood transfusion. The hemoglobin values before transfusion (7.2 +/- 0.1
      g%) and at discharge (9.8 +/- 0.1 g%) were lower in 1991; transfused patients
      received similar amounts of blood in the 2 years. Endoscopic hemostatic therapy
      was used in 25% of patients with ulcers in 1991 and in none in 1981. Rates of
      rebleeding (including patients readmitted for recurrent bleeding within 1 week of
      discharge) and surgery were similar. Mortality was 2.8% in 1991, similar to the
      1981 death rate. Because of the excellent 1991 patient outcome, we continue to
      care for most patients with acute nonvariceal UGI bleeding with urgent endoscopy
      and short hospitalization.

PMID- 7806827
TI  - Why do patients seek a second opinion or alternative medicine?
AB  - The objectives of the study were (a) to determine psychosocial determinants of
      two measures of health care use: seeking a second opinion and alternative
      medicine use, and (b) to assess whether changes in these two measures of health
      care use had taken place during the past 4 to 5 years. All patients attending a
      university-based gastroenterology clinic were asked to complete a self
      administered questionnaire. The response rate was 83% (N = 341). Health locus of
      control, scepticism toward medicine, satisfaction with health care, and perceived
      health status were included as potential determinants. Sixteen percent (21) of
      the new patients (95% confidence interval, 10.0-22.8) sought a second opinion
      compared to 7.5% (95% confidence interval, 4.3-10.7) 5 years ago. Seeking a
      second opinion was negatively related to internal locus of control, perceived
      health status, and demanding to know all details of treatment. Eight percent (28)
      of all patients (95% confidence interval, 5.3-11.1) saw an alternative
      practitioner for the same problem for which they saw the gastroenterologist
      compared to 9% (95% confidence interval, 6.2-12.8) 4 years ago. Using alternative
      medical care was positively related to scepticism toward conventional medicine
      and negatively related to perceived health status and satisfaction with clinic
      physicians. Knowledge about the incidence and determinants of these behaviors
      provides valuable information for clinicians in communicating with their patients
      and may eventually result in cost containment.

PMID- 7806829
TI  - Hyperbaric oxygen for perianal Crohn's disease.
AB  - Perianal involvement in Crohn's disease is common (< or = 50%), distressing, and
      frequently refractory to treatment. Clinical features include painful induration
      and stenosis, discharging fistulas, and fissures. The pathogenesis of these
      lesions is unclear, but local ischemia and secondary anaerobic infection may play
      a role. Following three sporadic reports of successful treatment with hyperbaric
      oxygen (HBO), we undertook a trial of this method in 10 patients with refractory
      perianal disease. These patients' perianal Crohn's disease had not responded to
      treatment that included local medications, salicylates, corticosteroids,
      metronidazole, or 6-mercaptopurine were treated. Treatment was administered in a
      hyperbaric chamber at a pressure of 2.5 atm absolute. Each session lasted 90 min,
      and each course consisted of 20 daily sessions. Complete healing occurred in 5
      patients after one to two courses. In an additional 2, after three courses, 1
      patient improved but did not heal, and 2 did not improve. No adverse effects were
      noted by any of the 10 patients. Follow-up of 18 months did not reveal any
      recurrence. These preliminary results confirm that HBO therapy is a safe and
      efficient therapeutic option for perianal Crohn's disease.

PMID- 7806828
TI  - Cytomegalovirus in upper gastrointestinal ulcers.
AB  - Cytomegalovirus (CMV), an important cause of severe infections in
      immunocompromised patients, can cause ulcerations anywhere in the
      gastrointestinal tract, most commonly stomach and colon. Only a few cases of CMV
      inclusions in gastrointestinal ulcers have been reported in normal hosts. We
      undertook a prospective study of the incidence of CMV in gastroduodenal
      ulcerations in immunocompetent patients. Thirty-eight patients who were referred
      for evaluation of dyspepsia, hematemesis, melena, guaiac-positive stools, or iron
      deficiency anemia and who had gastric or duodenal ulcerations without stigmata of
      recent hemorrhage or visible vessel were enrolled in the study. Six biopsies
      obtained from the ulcer base and margin were submitted for histologic
      examination, shell-vial viral cultures, and monoclonal antibody testing. Thirty
      two patients had gastric ulcer and six had duodenal bulbar ulcer ranging in size
      from 8 to 20 mm in diameter. Forty-four percent of patients had been taking
      aspirin or nonsteroidal antiinflammatory drugs (NSAIDs) within 10 days of ulcer
      discovery. Evaluation of all biopsies in 38 patients failed to document any
      evidence of CMV by light microscopy, viral cultures, or monoclonal antibody
      testing. CMV infection is uncommon in the gastrointestinal tract of
      immunocompetent patients with gastroduodenal ulcers. Even within areas of
      previous mucosal injury induced by nonsteroidal drugs, no evidence of CMV
      "superinfection" was found. We conclude that CMV infection is not a significant
      factor in routine peptic or NSAID-induced ulcer disease, and the discovery of CMV
      inclusions in gastroduodenal ulcerations should lead to a search for an
      immunocompromised state.

PMID- 7806830
TI  - Steatocrit: a reliable semiquantitative method for detection of steatorrhea.
AB  - Steatocrit is a semiquantitative method for determination of fat content in fecal
      samples. Previous studies, mostly performed in children, reported controversial
      results. The aim of our study was to compare the determination of fat content in
      148 fecal samples by two methods: the conventional van de Kamer and the
      steatocrit. Seventy-seven fecal samples had steatorrhea (> 7 g/day). The upper
      normal limit for the steatocrit (determined by the mean +/- 2 SD of samples
      without steatorrhea) was 2.1%. The steatocrit showed a sensitivity of 87%,
      specificity of 97%, and positive and negative predictive values of 97 and 87%,
      respectively. When fecal fat excretion > 20 g/day was evaluated, sensitivity
      increased to 98%. A significant linear correlation was found between steatocrit
      and the quantitative chemical method (r = 0.80; p < 0.0001). In conclusion, the
      steatocrit is satisfactory in the discrimination of patients with and without fat
      malabsorption. It is a simple, rapid, inexpensive, and reliable semiquantitative
      test that can be used when other methods are impractical.

PMID- 7806831
TI  - The distribution of lymph node metastases in right-sided colon cancer.
AB  - We reviewed the surgical results of 57 patients with right-sided colon carcinoma
      (RCC) with special reference to lymph node metastasis. In 45 cured patients, 25
      showed no lymph node metastasis (n0), 19 showed a low or moderate degree of lymph
      node metastasis (n1, n2), and only one showed a high degree of lymph node
      metastasis (n3). As for the remaining 12 cases, the reasons that operation did
      not lead to a cure were liver or lung metastasis (66%), peritoneal spread (17%),
      or extensive lymph node metastasis (17%). Among these patients, only one may have
      died from insufficient lymph node dissection (R2 < n3). The presence of lymph
      node metastasis was predicted by the serum carcinoembryonic antigen level (> 3.0
      ng/ml) and histologic type (other than well differentiated). These results
      indicate that complete removal of the group 1 and 2 nodes (R2 dissection) is a
      feasible operation for RCC.

PMID- 7806832
TI  - Treatment of type C chronic active hepatitis with interferon-alpha 2a. Treatment
      duration does not influence biochemical remission but does decrease the relapse
      rate.
AB  - Few data are as yet available on the influence of interferon (IFN) treatment
      duration on biochemical remission and posttreatment relapse of chronic type C
      hepatitis. We investigated whether duration of recombinant IFN-alpha 2a treatment
      influences the remission and relapse rates in type C chronic active hepatitis
      (CAH). Sixty-two CAH patients were randomly assigned to receive 3 MU of i.m.
      recombinant IFN-alpha 2a three times per week for either 3 (group A, 32 patients)
      or 6 (group B, 30 patients) months. A complete biochemical remission was
      cumulatively observed in 62.5 and 63.3% of patients in groups A and B,
      respectively (p = NS). One and two patients in groups A and B, respectively,
      showed a biochemical relapse during treatment. In all cases biochemical remission
      was observed within the first 3 months of treatment. Among responders, 84.2 and
      52.9% (p = 0.04) cumulatively had relapses in groups A and B, respectively. We
      conclude that IFN treatment duration does not influence the biochemical remission
      rate in type C CAH, but lowers the relapse rate of those who are treated for a
      longer period. The IFN treatment should be stopped if the patient is a
      nonresponder after 3 months of treatment. In responders, treatment should be
      continued for at least 6 months.

PMID- 7806833
TI  - A comparative clinical study of idiopathic portal hypertension, extrahepatic
      portal vein thrombosis, and cirrhosis.
AB  - The relationship between idiopathic portal hypertension (IPH) and extrahepatic
      portal vein thrombosis (EPVT) remains controversial. In a retrospective study, we
      compared the clinical features of 21 patients with IPH, 27 with EPVT, and 38 with
      liver cirrhosis (LC). The variables with statistical difference between IPH and
      EPVT were age (38 +/- 17 years versus 29 +/- 14, respectively; p < 0.05), and 5
      year survival (72 versus 92%, respectively; p < 0.05). The other clinical and
      laboratory variables had similar distribution in IPH and EPVT. LC patients were
      older than those in the other groups (48 +/- 13 years, p < 0.05), and had a
      poorer 5-year survival (60%, p < 0.05). Furthermore, LC patients had clinical
      features of liver failure in a higher proportion than the other groups did. The
      results suggest that IPH, EPVT, and LC are separate clinical entities.

PMID- 7806834
TI  - Endoscopic ultrasonography with color Doppler function in the diagnosis of rectal
      variceal bleeding.
AB  - Extraesophagogastric variceal bleeding in patients with portal hypertension is
      rare, but has been reported after endoscopic injection sclerotherapy (EIS) for
      esophageal varices. Here, we report rectal variceal hemorrhage following EIS.
      Endoscopic ultrasonography with color Doppler function (EUSCD) was useful for the
      diagnosis of rectal varices and complete hemostasis was obtained with EIS. A
      review of the literature since 1980 revealed a total of 15 patients, including
      ours, with extraesophagogastric variceal bleeding following EIS. This suggests
      EIS is the principal emergency treatment for bleeding rectal varices.

PMID- 7806835
TI  - Cholesterol emboli in a colonic polyp.
AB  - Cholesterol emboli usually occur after vascular surgery or angiographic
      procedures in patients with extensive arteriosclerosis. Atheroemboli also occur
      spontaneously in patients receiving anticoagulant drugs. Ischemic colitis,
      gastric hemorrhage, and acute pancreatitis are the more common gastrointestinal
      manifestations of cholesterol emboli. Here I report, for apparently the first
      time, cholesterol emboli in a colonic polyp.

PMID- 7806836
TI  - Reactive hemophagocytic syndrome simulating acute hepatitis. A case due to
      hepatic peripheral T-cell lymphoma.
AB  - The reactive hemophagocytic syndrome may mimic acute hepatitis, as we report
      here. It should be considered when hepatitis is accompanied by high fever,
      progressive cytopenias, and weight loss, with or without adenopathy and striking
      lactate dehydrogenase elevation. Bone marrow, lymph node, or liver biopsy are
      necessary to confirm the diagnosis. Recognition is important, because the
      syndrome has multiple potential causes amenable to therapy. Preliminary reports
      suggest that high-dose corticosteroid therapy is useful in suppressing cytokine
      stimulated fever and hemophagocytosis, whatever the underlying cause.

PMID- 7806837
TI  - Recurrent fulminant liver failure caused by hepatitis B virus after liver
      transplantation.
AB  - We report a 44-year-old man who received a liver graft because of fulminant liver
      failure due to hepatitis B virus. Nine months later a new episode of acute
      hepatitis B followed a fulminant course and led to another transplantation. The
      patient died due to invasive aspergillosis and multiorgan failure 3 weeks after
      the second transplant. This case reveals that hepatitis B virus reinfection may
      also occur after transplantation in patients with fulminant hepatitis B and under
      immunosuppression circumstances. Although immunoprophylaxis with hepatitis B
      hyperimmune globulin may prevent hepatitis B reinfection, it does not guarantee
      complete protection even in patients presumed to have low risk of reinfection.
      Finally, this case confirms the high risk of fungal infections in patients with
      fulminant liver failure and the need to establish early antifungal therapy.

PMID- 7806838
TI  - Cholestatic hepatitis after ingestion of chaparral leaf: confirmation by
      endoscopic retrograde cholangiopancreatography and liver biopsy.
AB  - The use of herbal and other "natural" health products by healthy and ill people
      is more common than is appreciated by many health care providers. Since most of
      these substances are not categorized as medicines, they are exempt from U.S.
      Government approval processes, and are essentially uncontrolled. In this article
      we describe a patient who developed painless jaundice, fatigue, and pruritus
      after taking chaparral tablets, 160 mg/day, for approximately 2 months. Serial
      liver biopsies and serum chemistries documented severe cholestasis and
      hepatocellular injury, i.e., a severe cholangiolitic hepatitis. Serum enzyme
      levels were markedly elevated: alk. phos. to four-fold, alanine aminotransferase
      and aspartate aminotransferase to 25-fold, total bilirubin to 30-fold, and gamma
      glutamyl transpeptidase to 35-fold. Endoscopic retrograde
      cholangiopancreatography showed smooth, but severely narrowed biliary ducts
      without sclerosing cholangitis, distal obstruction, tumor, or stenosis. The
      diagnosis remained in doubt until the publication of two cases of chaparral
      hepatotoxicity. Because of the similarity of our patient's illness to those cases
      we concluded that chaparral was almost certainly the cause. Chaparral, also known
      as creosote or greasewood, is used by some practitioners to treat a diverse group
      of ailments including ethanol withdrawal. This report should heighten the
      awareness by primary care physicians and gastroenterologists that any chaparral
      herbal preparation is a potential hepatotoxin that can lead to serious
      illness.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7806839
TI  - The development of cimetidine: 1964-1976. A human story.
AB  - There was still controversy regarding the physiology of acid secretion in 1964
      when a team at Smith Kline & French Laboratories in England started a project to
      prove the existence of more than one receptor for histamine and to find a
      substance capable of blocking the effects not blocked by the commonly used
      antihistamines. The team was convinced that histamine was the final mediator of
      acid secretion. After 8 years, James Black and his coworkers published evidence
      of the first histamine2-receptor antagonist, burimamide. As this substance was
      not suitable for oral therapy, the research continued. Metiamide was synthesized
      with promising clinical effects but questionable safety. The final answer was
      cimetidine (Tagamet), approved in England in November 1976. Cimetidine was a
      breakthrough in the treatment of peptic ulcers. In this article I focus on the
      human factors lying behind many of the decisions made during the years of
      research. Without personal courage under stressful conditions, the H2-receptor
      antagonists might never have reached the market.

PMID- 7806840
TI  - Upper gastrointestinal endoscopy can be a reliable screening tool for celiac
      sprue in adults.
AB  - In our study, we evaluated whether the combination of two endoscopic
      abnormalities in the duodenum (the "mosaic" appearance and loss of duodenal
      folds) is significantly associated with duodenal villous atrophy secondary to
      celiac sprue in adults. Fourteen patients referred for esophagogastroduodenoscopy
      for suspected celiac sprue and 146 for suspected peptic disease were enrolled in
      the study. At least one of the two endoscopic duodenal abnormalities was observed
      in all 10 untreated celiac patients but in only one of the dyspeptic patients.
      The sensitivity and specificity were 100 and 99.3%, with positive and negative
      predictive value of 90.9 and 100%, respectively. Such good results suggest that
      duodenal endoscopy can be a screening procedure for celiac sprue in patients who
      are undergoing endoscopy for other reasons.

PMID- 7806841
TI  - Adenocarcinoma of midstomach. Clinical and pathoanatomic relation to lymph node
      metastases.
AB  - A detailed clinical and anatomic-pathological study of lymph node (LN) metastases
      from adenocarcinoma of the midstomach is lacking. To such an end, we
      prospectively evaluated 100 patients who underwent radical gastrectomy. A total
      of 3,394 LNs were removed with an average of 34 per specimen (range, 10-105).
      Forty-seven patients (47%) had involved LNs. The most frequent LNs involved were
      those along the lesser curvature (38%), greater curvature (23%), left gastric
      artery (19%), infrapyloric (16%), above the common hepatic artery (13%),
      suprapyloric (11%), and right paracardia (9%). When tumors involved the upper
      stomach, the frequency of LN metastases along the splenic artery and in the
      splenic hilum was 11.8%. Tumors along the lesser curvature or on the anterior or
      posterior walls had splenic hilar LN metastases in 10%, whereas of tumors
      involving the whole circumference, 16.7% showed with metastases. Four of 33
      patients (12.1%) with early cancer had LN metastasis confined to the perigastric,
      left gastric artery, and above the common hepatic artery. The LN metastases were
      closely related to the depth of cancer invasion, location, size, gross
      appearance, and histology of the tumor.

PMID- 7806842
TI  - Pharmacobezoars--the irony of the antidote: first case report of nifedipine XL
      bezoar.

PMID- 7806843
TI  - Colonoscopic dissolution of a barolith.

PMID- 7806844
TI  - Pyoderma gangrenosum as a complication of percutaneous endoscopic gastrostomy
      tube insertion.

PMID- 7806845
TI  - Interferon-induced pancreatic injury.

PMID- 7806846
TI  - Vanishing bile duct syndrome occurring after carbamazepine administration: a
      second case report.

PMID- 7806847
TI  - Consciousness: how does it relate to health?
AB  - The purpose of this article is to clarify the concept consciousness as it relates
      to human health and invite nurses to examine a variety of perspectives on the
      concept that may influence practice, education, and research. A review of
      American nursing, medical, psychological, and philosophical literature reveals a
      considerable range of theories that seem to connect, forming a broad foundation
      for further study. Initial analysis of the concept yields a working definition
      that consciousness is the fundamental and thoroughly pervasive implicit field of
      all existence, both seen and unseen. Additionally, the North American Nursing
      Diagnosis Association human response patterns were found to provide a useful set
      of empirical referents. Further exploration and testing of these referents may
      stimulate important insights into the fundamental domains of nursing.

PMID- 7806848
TI  - We are the stories we tell: narrative knowing in nursing practice.
AB  - In recent years, nurses have come to (re)value narrative knowing: the knowledge
      transmitted in the stories that human beings have told each other since the
      beginning. Narratives area generally understood to be stories with a certain
      dynamic structure and shape directed toward achieving wholeness, or health. In
      this article, the author considers why caregivers have become interested in
      narratives, the nature and function of stories for patients, the location of
      stories in the diagnostic and healing functions of the nurse, and the
      significance of stories for holistic nursing practice.

PMID- 7806849
TI  - Defining and implementing a standard for therapeutic relationships.
AB  - As family-centered care gradually became the norm in care of infants and
      children, relationships between staff, patients, and families became more
      complex. Because the complexity of these relationships was rarely, if ever,
      addressed, widely divergent, sometimes detrimental, behaviors evolved.
      Therapeutic relationships, which promote caring and define relationships with
      patients and families, are a positive and professional means to promote a
      family's control over their own child's health. This article describes assessment
      of nurse/patient/family relationships using family systems theory as a framework.
      The experience of implementing a culture shift toward therapeutic relationships
      is described.

PMID- 7806850
TI  - Dynamics of consciousness and healing.

PMID- 7806851
TI  - The healing web: an expansion of consciousness.
AB  - The search for community manifest in society today reflects the apparent
      alienation, unconnectedness, and superficiality of modern life. A group of nurses
      in education and service created a community filled with caring and trust that
      designed the Healing Web, a transformative model for nursing. The web was
      established to create partnerships that will transform the health care paradigm
      of society. By establishing and maintaining a healing community within nursing
      and the larger universe, wholistic and integrative life will be restored.

PMID- 7806852
TI  - The healing process of presence.
AB  - Therapeutic relationships help provide the milieu for the nurse and the patient
      to gain insights into the essence of disease and the nature of healing. In
      building a foundation on which to be in optimally responsive relationships,
      nurses at Riverside Methodist Hospitals in Columbus, Ohio, participate in a 2-day
      course that explores and names how we bring ourselves as gifts to others as well
      as to ourselves in the dynamic of therapeutic presence. The following article
      reviews the literature on presence, provides a course description and contents on
      presence, and assists nurses in incorporating principles of presence into nursing
      practice.

PMID- 7806853
TI  - Music for the dying: a personal account of the new field of music-thanatology-
      history, theories, and clinical narratives.
AB  - Music-thanatology is a palliative medical modality employing prescriptive music
      to tend the complex physical and spiritual needs of the dying. "Infirmary music"
      was an intimate expression of French monastic medicine in 11th-century Cluny and
      anticipated the holism of both the hospice and palliative medical movements by
      almost 800 years. Although no longer an expression of any institutional religious
      identity, music-thanatology is nevertheless concerned with the possibility of a
      blessed death and the gift that conscious dying can bring to the fullness of
      life. Music-thanatology interns seek to integrate and model these contemplative
      and clinical values in daily practice: 18 interns deliver prescriptive music in
      bedside vigils serving the dying in home, hospital, and hospice settings with
      great effectiveness in oncology, respiratory illnesses, the slow degenerative
      diseases, and AIDS. This article is submitted to nurses to serve as an
      introduction to the field of music-thanatology, providing readers with a brief
      history, meaningful clinical narratives, some of the musical theories involved,
      research concerns (archival and medical), and milestones to be addressed for the
      future implementation of music-thanatology in hospitals and hospices and
      communities across the nation.

PMID- 7806854
TI  - Reawakening spirit in clinical practice.
AB  - This article describes processes for incorporating spirituality into clinical
      nursing practice. Spirituality is viewed as a unifying force manifested in the
      Self, which is expressed and experienced in the context of caring connections
      with oneself, others, nature, and God/life force. Spirituality relates to an
      inner knowing and source of strength reflected in one's being, one's knowing, and
      one's doing. The nurse's intentional, caring presence with clients makes possible
      the speaking and hearing of spiritual concerns. Such concerns are revealed in the
      context of one's life story. Nurturing the nurse's own spirit is essential for
      responding to the spirit in any interaction. Nurses frequently deal with issues
      of spirituality but may not label them as such. This article suggests processes
      through which nurses may more clearly identify spiritual issues. Spirit is
      understood to be both the source of and a manifestation of one's spirituality. By
      reawakening spirit in clinical practice, nurses will be more effective providers
      of holistic nursing care.

PMID- 7806855
TI  - Health care crisis.

PMID- 7806856
TI  - The dying man, the young physician and health reform.

PMID- 7806857
TI  - Licensing board's duty: to protect the public. Interview by Bob Carlson.

PMID- 7806858
TI  - Peer review shifts focus to patterns of care.

PMID- 7806859
TI  - The new frontier for physicians: revenue-focused.

PMID- 7806860
TI  - The death of Wolfgang Amadeus Mozart.

PMID- 7806861
TI  - How to settle a dispute without going to court.

PMID- 7806862
TI  - Intraoperative brain mapping during tumor resection from critical areas of the
      brain.

PMID- 7806863
TI  - Maternal mortality in Indiana: a report of maternal deaths in 1992.

PMID- 7806864
TI  - Protective over-shoes are unnecessary in a day surgery unit.
AB  - The lack of agreement on the use of over-shoes tends to perpetuate the ritual of
      their use in general operating theatres. However, the limited evidence which
      supports their use in such settings is not applicable in a Day Surgery Unit where
      their use is not recommended. In order to reduce overt contamination in the unit
      theatre, a local protocol should be drawn up specifying the use of designated day
      unit footwear for those that remain within the unit and for all persons entering
      the operating theatre.

PMID- 7806865
TI  - Nurses' hand decontamination practice: results of a local study.
AB  - Cross-infection in hospital occurs mainly via hands. Hand washing is the most
      effective means of prevention, yet it has been reported that hands are washed too
      seldom, often inappropriately and that technique is poor. However, these claims
      are often made without explaining precisely how data were collected. This study
      employed more rigorous criteria than earlier research to judge the
      appropriateness and technique of nurses' hand contamination. During the 2 h that
      they were observed nurses decontaminated hands after 28.7% patient contacts. The
      data were then reanalysed so that only those activities likely to result in heavy
      contamination were examined. This revealed that such 'essential' decontaminations
      were performed on 49.8% occasions. Differences were found between hospitals
      related to the availability of hand decontaminating agents, particularly when
      nursing workload became high. A scoring system to assess technique was developed
      for the study. Mean score was 8.6 out of 12. Technique was superior for nurses
      employed in intensive care units regardless of the hospital in which data were
      collected (P < 0.0001). Nurses' knowledge of infection control was poor, but
      those with more knowledge decontaminated hands more appropriately (P < 0.004),
      although they did not have a better technique. It is recommended that future
      research move beyond mere description, with its inevitable conclusion that
      clinical staff should improve performance, turning toward the identification of
      local barriers to effective practice. This could be followed by improvement in
      resources and educational intervention should these emerge as problematic.

PMID- 7806866
TI  - An outbreak of group C streptococcal infection in a maternity unit.
AB  - An outbreak of Group C streptococcal infection (Streptococcus equisimilis
      serotype T204) occurred in a Maternity Unit in Durham over a 2-week period. The
      outbreak strain possessed an M-protein antigen identical to that found in a
      previously reported Maternity Unit outbreak. Seven patients in total were
      affected, and in two patients infected perineal wounds took several weeks to
      heal. The source of the outbreak appeared to be a patient who developed a
      perineal wound infection and who subsequently returned to the ward for
      reassessment. Environmental contamination is likely to have been the reservoir of
      infection for the subsequent patients. The outbreak was controlled by applying
      strict infection control procedures and establishing a high standard of routine
      cleaning.

PMID- 7806867
TI  - Epidemiological markers of Acinetobacter baumannii clinical isolates from a
      spinal cord injury unit.
AB  - During a period of 28 months, 114 isolates of Acinetobacter baumannii obtained
      from urine samples of 57 patients, were recovered in a Spinal Cord Unit; an
      unusual increase in the number of A. baumannii isolates was observed between
      February 1991 and January 1992. Six different typing methods [biotyping,
      antimicrobial susceptibility, whole cell and cell-envelope protein analysis,
      plasmid analysis and chromosomal DNA analysis by pulsed-field gel electrophoresis
      (PFGE)] were used to study the isolates to establish any potential relationships
      among them. Chromosomal DNA analysis by digestion with ApaI and separation of the
      fragments by PFGE was the most powerful tool to determine the relatedness of
      isolates. The results suggest that the isolates from 1991 and 1992 may have
      originated from strains present in 1990 that subsequently acquired resistance to
      amikacin and tobramycin during the epidemic.

PMID- 7806868
TI  - Polymicrobial and monomicrobial bacteraemic urinary tract infection.
AB  - Polymicrobial blood or urine cultures in bacteraemic urinary tract infection
      (UTI) are relatively common. There is, however, very little information available
      on the clinical and bacteriological features that distinguishes between
      monomicrobial and polymicrobial urosepsis. During 1980-84, 68 of 198 episodes
      (34%) of urosepsis with at least one identical organism in blood and urine, had
      multiple growth in either one or the other. Comparison between monomicrobial and
      polymicrobial infectious episodes showed that the latter were more often hospital
      acquired and more frequently associated with urinary catheters. Pseudomonas
      aeruginosa was more often associated with polymicrobial than with monomicrobial
      infections, whereas Escherichia coli was more common in monomicrobial infections.
      Mortality was higher in polymicrobial infections, and was further increased if
      multiple organisms grew from blood rather than from urine. Thus, there are
      clinical, microbiological and prognostic characteristics that distinguish
      polymicrobial from monomicrobial bacteraemic UTIs.

PMID- 7806869
TI  - Endoscopy: disinfectants and health. Report of a meeting held at the Royal
      College of Surgeons of England, February 1993.

PMID- 7806870
TI  - Antibiotic prophylaxis for urodynamic testing in patients with spinal cord
      injury: a preliminary study.
AB  - This study was performed in order to: (i) determine the incidence of symptomatic
      urinary tract infection (UTI) in patients with spinal cord injury after
      urodynamic testing; (ii) evaluate the role of antibiotic prophylaxis for such a
      procedure; and (iii) investigate whether pre-existing bacteriuria predisposes to
      the development of symptomatic UTI after urodynamic testing. Forty patients were
      prospectively randomized in a double-blind fashion to receive a 3-day oral course
      of either ciprofloxacin (18 patients) or placebo (22 patients), beginning 2 days
      prior to the urodynamic procedure. None of 18 (0%) patients who received
      ciprofloxacin developed symptomatic UTI within 5 days after the procedure
      compared with three of 22 (14%) subjects randomized to the placebo group; the
      protective efficacy of antibiotic prophylaxis, however, did not attain
      statistical significance (P = 0.24). None of the three bacterial isolates that
      were responsible for symptomatic infection were grown in corresponding urine
      cultures prior to the procedure. These findings may serve as a pilot for a larger
      study.

PMID- 7806871
TI  - A comparison of the bactericidal activity of 'Phoraid 6000' and 'Clearsol'
      disinfectants.
AB  - The bactericidal activity of 'Phoraid 6000' and 'Clearsol' disinfectants was
      evaluated using suspension and surface tests. In suspension tests, 2% 'Phoraid'
      achieved a > 5 log10 reduction of Pseudomonas aeruginosa, Escherichia coli and
      Staphylococcus aureus in 1 min in the absence of blood, but negligible activity
      in 10 min in the presence of 1% blood; 10% 'Phoraid' exhibited no useful activity
      in the presence of 5% blood and 20% Phoraid no useful activity in the presence of
      10% blood. In contrast, 'Clearsol' was very resistant to neutralization by blood:
      1% 'Clearsol' achieved a > 5 log10 reduction of P. aeruginosa, E. coli and S.
      aureus in 5 min in the presence of > or = 70% blood. In surface tests, undiluted
      'Phoraid 6000' failed to disinfect wet blood contaminated with either P.
      aeruginosa, E. coli or Proteus vulgaris in the 2-min exposure period. 'Clearsol'
      gave mixed results: 2% 'Clearsol' was very effective but the standard use
      dilution of 1% proved inadequate.

PMID- 7806872
TI  - The multiple value of surveillance cultures: an alternative view.

PMID- 7806873
TI  - Mupirocin-resistant MRSA.

PMID- 7806874
TI  - Tropical pyomyositis.

PMID- 7806875
TI  - p24 antigenaemia in HIV-1 infected Brazilians correlates with other markers of
      disease progression.

PMID- 7806876
TI  - A case of disseminated toxoplasmosis-value of PCR for the diagnosis.
AB  - Extracerebral toxoplasmosis has recently gained greater attention as a
      consequence of the AIDS epidemic. Serological techniques are unreliable, while
      isolation of the parasite is either time-consuming or insensitive. We here report
      a case of disseminated toxoplasmosis in a patient with AIDS. Diagnosis was
      suggested by serological tests and confirmed by PCR and Southern blot
      hybridisation or nested PCR. Detection of specific DNA was feasible in
      bronchoalveolar fluid, blood, serum and tissue samples. Direct detection of
      parasite-specific DNA by PCR and by nested PCR proved to be a promising,
      sensitive and rapid method for the diagnosis of disseminated toxoplasmosis,
      enabling us to promptly initiate specific treatment.

PMID- 7806877
TI  - Association between polyomaviruria and microscopic haematuria in bone marrow
      transplant recipients.
AB  - The association of polyomaviruria and microscopic haematuria was studied by the
      use of electron microscopy (EM) and the polymerase chain reaction (PCR) in bone
      marrow transplant (BMT) recipients. The incidence of BK virus (BKV) and JC virus
      (JCV) excretion was further elucidated by means of restriction enzyme analysis of
      the PCR products. Polyomaviruses were detected in 43 (51.2%) of the 84 samples,
      13 (30.2%) of which had a virus concentration detectable by EM. By typing with
      BamHI cleavage, 29 (67.4%) of the 43 positive patients were found to be excreting
      only BKV and the remaining 14% (32.6%) were excreting both BKV and JCV.
      Microscopic haematuria was present in 17 (20.2%) of 84 urine samples collected
      from different patients within 4 months post-transplant. The incidence of
      microscopic haematuria was significantly higher, 34.9% (P < 0.01), in patients
      with polyomaviruria than in those without (4.9%) but no difference was observed
      between the BKV-excreting and BKV/JCV-co-excreting patients. Microscopic
      haematuria was not present, however, in 53.8 and 65.2% of polyomavirus-excreting
      patients when virus was detected by EM and PCR respectively. While most episodes
      of microscopic haematuria observed were self-limiting and asymptomatic, three
      patients excreting polyomavirus had symptoms of cystitis and one of them had
      renal impairment that was otherwise unexplained. We thus conclude that
      polyomaviruses probably contribute to damage of urinary tract tissue in some BMT
      recipients.

PMID- 7806878
TI  - Nosocomial infection with Candida albicans in a pancreatic transplant recipient
      investigated by means of restriction enzyme analysis.
AB  - Restriction enzyme analysis (REA) of total DNA was used in order to investigate
      the possible transmission of Candida albicans from the grafted pancreas in a
      woman with a kidney-pancreas transplant. A strain of Candida albicans was
      recovered from the pancreas-transplant preservation medium cultured routinely
      before transplantation. Four infecting isolates and one vulval isolate were
      recovered from the recipient in the early post-operative stage. In addition, 12
      unrelated control strains were studied for comparison. By means of EcoRI and
      HinfI, restriction patterns of the isolates recovered from the preservation
      medium and from the patient were found to be identical (100% similitude according
      to Jaccard's coefficient) apart from that of the strain isolated from the vulva.
      HinfI gave two characteristic fragments of 5.9 and 4.6 kb. In contrast, the 12
      control strains generated 12 different patterns. The percentage of similarity
      between the patterns of the infecting strains and those of the control and the
      vulval strains was less than 60%. These findings provide evidence of transmission
      of the infecting strain via the pancreas transplant and the nosocomial nature of
      infection.

PMID- 7806879
TI  - Risk of perinatal transmission of Chlamydia trachomatis by mode of delivery.
AB  - We compared the transmission rate of Chlamydia trachomatis infection from
      infected women to their infants after various modes of delivery. After vaginal
      birth, Chlamydia trachomatis was isolated from 58 of 125 infants with a cephalic
      presentation, and serological evidence of chlamydial infection was found in
      another eight. C. trachomatis was isolated from the only infant with a frank
      breech presentation. After Caesarean birth, C. trachomatis was isolated from two
      of 10 infants born after rupture of the membranes and from one of six without
      prior rupture of the membranes. No serological evidence of infection was found in
      any of the culture-negative infants born by Caesarean section. By survival
      analysis, rates of transmission were significantly lower after Caesarean section
      with rupture of the membranes before delivery than after vaginal delivery.
      Infants born to infected women are at risk of C. trachomatis infection regardless
      of route of delivery.

PMID- 7806880
TI  - A review of the clinical presentation, laboratory features, antimicrobial therapy
      and outcome of 77 episodes of pneumococcal meningitis occurring in children and
      adults.
AB  - Seventy-seven episodes of pneumococcal meningitis in 69 patients were reviewed.
      Twelve (15.6%) episodes occurred in those over 60 years old, 14 (18.2%) in
      patients between 10 and 60 years, 22 (28.6%) in patients between 2 and 10 years
      and 29 (37.7%) in those under 2 years. Overall mortality was 13.0% (10/77) and
      age of > 60 years was significantly associated with mortality (P < 0.05). Twelve
      episodes resulted in disabilities, eight of which were in those under 2 years,
      and took the form of hearing impairment in nine. Many patients had predisposing
      conditions with aural pathology, malignancy and diabetes mellitus being commonest
      in those over 10 years of age and aural pathology, preceding viral infection,
      renal disease, sinusitis or recent lower respiratory tract infection commonest in
      those aged between 2 and 10 years. Three of five patients with recurrent
      meningitis had CSF leaks. The most common features at presentation were fits,
      irritability, diarrhoea, and bulging fontanelles in those under 6 months;
      vomiting, drowsiness and poor feeding in those between 6 months and 2 years; neck
      stiffness, vomiting and drowsiness in those between 2 and 10 years while neck
      stiffness, focal neurology, headache and vomiting were commonest in those over 10
      years old. Fever was common in all age groups as were foci of infection outside
      the CSF, with chest infections being significantly associated with mortality (P <
      0.05). Of the laboratory parameters measured, low platelets (< 100 x 10(9)/l and
      high blood urea (> 7 mmol/l) were associated with mortality (P < 0.05). Blood
      cultures grew Streptococcus pneumoniae in 79.7% patients. Seventy-four (96%)
      patients had CSF taken of which 81% had gram films which were positive and
      interpreted correctly as showing pneumococci. Pneumococci were grown in 87.8% CSF
      cultures and all were sensitive to penicillin but a single isolate was
      chloramphenicol resistant. Many different antimicrobial drugs were used but
      penicillin plus chloramphenicol was the most commonly employed after the results
      of CSF microscopy were known and penicillin alone after culture results were
      available. Penicillin mono-therapy was associated with a low mortality.

PMID- 7806881
TI  - Discrimination by means of pulsed-field gel electrophoresis between strains of
      Campylobacter jejuni Lior type 4 derived from sporadic cases and from outbreaks
      of infection.
AB  - The cleavage patterns of the genomic DNA in 42 strains of Campylobacter jejuni
      Lior type 4, obtained from sporadic cases and from outbreaks of infection were
      analysed by means of pulsed-field gel electrophoresis (PFGE). The cleavage of DNA
      with SmaI and SalI restriction enzymes showed 16 distinct fragment patterns in 20
      sporadic isolates, indicating that they were heterogeneous. On the other hand,
      the patterns of 22 isolates derived from two outbreaks showed the same unique
      restriction patterns, respectively. PFGE may therefore prove useful for
      subclassifying strains of C. jejuni Lior type 4 and for discriminating between
      strains derived from sporadic cases and those derived from outbreaks of
      infection.

PMID- 7806882
TI  - An analysis of 900 consecutive admissions to a regional infection unit.
AB  - A total of 900 consecutive admissions to the Regional Infection Unit at the City
      Hospital Aberdeen in 1991 have been analysed and the results compared with a
      similar study during 1980 and 1981. The annual number of admissions increased
      from 605 to 900, of which 72% in 1991 had proven infections compared with 60% a
      decade earlier. More patients were admitted with gastroenteritis, tonsillitis and
      soft tissue infection in 1991 and fewer with non-infectious jaundice. HIV-related
      conditions contributed 4% of the admissions and 29% of the mortality. Brucellosis
      disappeared as a reason for requesting hospital admission in North East Scotland.

PMID- 7806883
TI  - Infection in immunocompromised patients with malignant blood disorders in a
      district general hospital.
AB  - The pattern and management of infection in immunocompromised patients over a
      period of 3 years in a district general hospital has been studied. A total of 222
      positive cultures was obtained in 607 episodes of suspected infection all
      involving patients with malignant blood disorders. Febrile episodes requiring
      intravenous antibiotics occurred in 248 instances involving 107 patients. The
      pattern of organisms cultured and the responses to various antibiotic regimes are
      reported. The costs of antibiotic therapy are considered in the light of the
      overall response. Of the patients studied, 54 died, infection having a likely
      causative or contributory part in 21 of them (less than 10% of infective
      episodes). We conclude that the infective complications of these disorders,
      particularly in older patients, can be efficiently managed in a district general
      hospital when full supportive facilities are available.

PMID- 7806884
TI  - Neonatal osteomyelitis in Down's syndrome due to non-encapsulated Haemophilus
      influenzae.
AB  - A case of neonatal osteomyelitis in a baby with Down's syndrome is described. The
      causative organism was a non-encapsulated Haemophilus influenzae biotype I, which
      was isolated from pus at the site of infection. This organism has not previously
      been reported as a cause of neonatal osteomyelitis.

PMID- 7806885
TI  - Mycoplasma hominis abscess secondary to respiratory tract infection.

PMID- 7806886
TI  - Primary meningococcal conjunctivitis and the need for prophylaxis in close
      contacts.
AB  - We present three cases of primary meningococcal conjunctivitis associated with
      systemic sepsis. The management of such patients should include combined topical
      and parenteral therapy with appropriate chemoprophylaxis for close contacts of
      cases.

PMID- 7806887
TI  - Respiratory syncytial virus infections in human beings and in cattle.
AB  - Respiratory syncytial virus (RSV) causes yearly outbreaks of respiratory disease
      in human beings and cattle all over the world. Most severe human respiratory
      syncytial virus (HRSV)-associated disease is observed in children less than 1
      year of age while most severe bovine respiratory syncytial virus (BRSV)
      associated disease is observed in calves less than 6 months of age. Two subgroups
      of HRSV have been identified. The existence of two subgroups of BRSV has been
      repeatedly suggested but is not yet well established. BRSV and HRSV are closely
      related antigenically but antigenic differences have been observed. Seasonal
      periodicity of RSV infection is usual with highest incidences in autumn and
      winter. Stress such as caused by movement, crowding and temperature changes are
      considered to play a role in bovine outbreaks. Human beings and cattle are the
      natural hosts of HRSV and BRSV, respectively. Primarily infected individuals are
      the most important source of RSV during outbreaks. The role of other species in
      the spread of HRSV and BRSV is unknown. Protective efficacy of maternally derived
      antibodies is considered to be incomplete. Such antibodies do not reduce shedding
      of virus after HRSV and BRSV infection. RSV is often transmitted by contact with
      nasal secretions but may also be transmitted by aerosols. Seroprevalence of HRSV
      and BRSV among adult human beings and cattle is over 70% and is always higher
      than it is among younger individuals. Both human beings and cattle of all ages
      may be reinfected with RSV. During BRSV reinfections, signs of respiratory tract
      disease and shedding of virus are seldom observed whereas these are common during
      HRSV reinfections. Persistent HRSV and BRSV infections in human beings and cattle
      have been suggested but have not so far been reported.

PMID- 7806888
TI  - Fulminant Capnocytophaga canimorsus (DF2) septicaemia and diffuse intravascular
      coagulation in hairy cell leukaemia with splenectomy.

PMID- 7806889
TI  - Listeria ivanovii infection.

PMID- 7806890
TI  - A fatal case of community-acquired Legionnaires' disease acquired from potable
      water.

PMID- 7806891
TI  - Vibrio cholerae O1 vibriocidal and anti-cholera toxin antibodies in O139 Bengal
      cholera patients.

PMID- 7806892
TI  - Phenotypically similar clones of serogroup B Neisseria meningitidis causing
      recurrent meningitis in a patient with total C5 deficiency.

PMID- 7806893
TI  - A lipopolysaccharide-binding hemagglutinin with specificity for acetylated
      aminosugars in the serum of the hermit crab Diogenes affinis (Henderson).
AB  - A naturally occurring hemagglutinin was detected in the serum of the hermit crab
      Diogenes affinis, and its erythrocyte (RBC) binding activities, physicochemical
      properties, and carbohydrate binding specificity were characterized. Both the
      hemagglutination profile and the pattern of cross-reactivity of the serum with
      different RBC types in cross-adsorption tests suggested a strong affinity of the
      serum agglutinin for rat RBC. Further analysis revealed that the agglutinin was
      specifically dependent on Ca2+ for its hemagglutinating activity and reversibly
      sensitive to EDTA. The activity was found to be stable between pH 6.0 and 7.5,
      heat-labile, and completely precipitable by ammonium sulphate or TCA, suggesting
      the proteinaceous nature of the serum agglutinin. In hemagglutination-inhibition
      assays, the serum agglutinin of D. affinis showed a distinct and unique
      specificity for acetyl group-containing carbohydrates and glycoprotein.
      Furthermore, the hemagglutinating activity of the serum agglutinin was also
      inhibited by lipopolysaccharide from Salmonella abortus equi, which might
      indicate a significant role of humoral agglutinin in the immune response of
      crustaceans against bacterial infection.

PMID- 7806894
TI  - Aquatic safety of Lagenidium giganteum: effects on freshwater fish and
      invertebrates.
AB  - Eleven freshwater species were exposed to a zoosporeproducing fungus, Lagenidium
      giganteum, with the goal of determining species sensitivity with standard and new
      test procedures. The tests included standard, 4-day acute exposures of
      cladocerans (Ceriodaphnia dubia, Daphnia pulex, and D. magna) and the fathead
      minnow (Pimephales promelas). Standard 7-day chronic exposures of C. dubia and a
      7-day embryo-larval exposure of P. promelas were also conducted. New, 4-day
      acute, methods were developed for mosquitos (Aedes aegypti), chironomids
      (Chironomus sp.), oligochaetes (Lumbriculus sp.), cyclopoid copepods, snails
      (Physa sp.), hydrozoans (Hydra sp.), and ostracods. To assess L. giganteum
      zoospore (z) infectivity, each test included daily bioassays with the mosquito
      (A. aegypti), a target organism. Four-day A. aegypti LC50s ranged from 81 to 516
      z/ml. Ceriodaphnia dubia acute test LC50s were as low as 6700 z/ml and the 96-hr
      LC50 from the chronic test was near 6250 z/ml with reproductive impairment at
      12,500 z/ml. Daphnia sp. were also susceptible, with LC50s near 7700 z/ml for D.
      pulex and 9400 z/ml for D. magna. Chironomus tentans was infected at
      concentrations of > or = 5000 z/ml, but mortality was low and an LC50 could not
      be calculated even after exposures to 50,000 z/ml. The 7-day, early life stage
      test with P. promelas produced reduced larva growth in most treatments. Several
      species (Hydra sp., L. variegatus, ostracoda, copepoda, Physa sp., and P.
      promelas) were not affected in acute tests at exposures of 50,000 z/ml. The data
      show, contrary to many reports, that L. giganteum may affect some nontarget
      aquatic species. The key to successful laboratory tests is monitoring and
      maintaining the zoospores infection capacity.

PMID- 7806896
TI  - Repeated isolation of Dermatophilus-like organism from leprosy material.
AB  - An organism having actinomycetoid type of colonies has been grown repeatedly in
      pure culture from leprosy material using a solid medium. The isolates obtained
      from different biopsies, skin scrapes and mouse foot-pad harvests were found to
      be similar to each other in the routine taxonomical tests and had many characters
      common with Dermotophilus congolensis. Similar growth could be obtained from a
      strain of M. leprae from armadillo and also from a DOPA-positive mycobacterium
      isolated previously from the blood of a leprosy patient.

PMID- 7806895
TI  - Specific reactivity of leukemia cells to polyclonal anti-PCB antibodies.
AB  - Bivalve molluscs such as the soft shell clam (Mya arenaria) develop leukemias in
      the hemolymph which are fatal. The prevalence of leukemia in Mya was evaluated
      using a murine monoclonal antibody which recognizes a leukemia-specific protein
      expressed by tumor cells. The reactivity with a polyclonal antibody to
      polychlorinated biphenyls (PCBs) of both normal circulating cells and tumor cells
      was also determined. Both leukemia prevalence and PCB reactivity were ascertained
      by flow cytometry. Analytical chemistry was used to quantitate the amount of
      Aroclor per tumor cell population and compared directly to flow cytometric
      results. Our results show that the prevalence of leukemia consistently exceeds
      60% when clams are retrieved from New Bedford Harbor, a site heavily contaminated
      with PCBs. Both normal circulating cells and tumor cells are extremely reactive
      with the PCB antibody. When clams from two other sites were compared with clams
      from New Bedford Harbor, both disease prevalence and cell reactivity to the PCB
      antibody were reduced. Our experiments are the first which use the flow cytometer
      to demonstrate PCBs in cell populations of marine invertebrates. Our results
      further demonstrate that the presence of polychlorinated biphenyls in vivo is
      directly correlated with environmentally linked leukemia.

PMID- 7806897
TI  - Sensory functions in limbs of normal persons and leprosy patients with peripheral
      trunk damage.
AB  - The threshold to touch was tested in hands and feet of normal persons using
      Semmes-Weinstein graded monofilament nylons. The minimum stimulus to which
      response could be elicited was nylon number 3.61 in palms and 4.31 in soles.
      These numbers relate to the logarithm of the force applied, 3.61 corresponding to
      0.217 gm force and 4.31 to 2.35 gm force respectively. The area of pain
      insensitivity complained by the patient more or less corresponds to that revealed
      by objective testing. It was interesting to observe that loss of pain sensitivity
      was confined to a smaller area compared to touch and thermal insensibility in the
      part innervated by the same nerve trunk.

PMID- 7806898
TI  - Intraocular pressure in leprosy patients without clinically apparent anterior
      segment pathology.
AB  - A widely prevalent notion is that intraocular pressures are generally lower in
      leprosy patients than in normal individuals. Applanation intraocular pressures
      were recorded in one hundred sixty-six leprosy patients who had no clinically
      visible anterior segment pathology and in one hundred and eleven healthy
      controls. Mean (SD) intraocular pressures in leprosy patients (13.6 (3.0) mm Hg)
      did not differ significantly from that of controls (13.1 (2.7) mm Hg). Eyes of
      only 1.5% of the leprosy patients had pressures of 7 mm Hg or less. Correlation
      coefficients (r) between age, sex and intraocular pressures were not
      statistically significant both in leprosy patients and in controls. No
      statistically significant differences in mean intraocular pressures were noted
      when leprosy patients were grouped according to the Ridley and Jopling
      classification. Duration of disease also did not affect the intraocular
      pressures. Neither did smear positivity or differing bacterial indices. This
      study questions the widely held belief that low intraocular pressures are a
      common feature in leprosy and contends that in the era of MDT where ocular
      complications associated with low intraocular pressures are thought to be less,
      the occurrence of low intraocular pressure may not be as common a phenomenon as
      it is believed to be.

PMID- 7806899
TI  - Some observations on patients from two leprosy colonies in north India attending
      a city clinic.
AB  - Fifty-eight patients (26 males - mean age 52.5 years, 32 females - mean age 58.5
      years) from two different leprosy colonies (Ambala and Jagadhari) were studied.
      Maximum number of the patients (48.4%) belonged to Uttar Pradesh. The clinical
      diagnosis was LLp:41(70.7%), LLs:14(24.2%), LL-burnt-out, BB-BL and BT: one each
      (1.7%). Mean duration of disabilities/deformities in these patients was 21.5
      years. A peculiar myokymic movement of periorbital muscles was observed in 20
      patients (34.5%). While dapsone monotherapy was continued in 55 patients, MDT
      (WHO-multibacillary regimen) was started in three patients. Vocational advice was
      given to 23 patients; and 35 (60.4%) patients were declared as "destitutes".

PMID- 7806900
TI  - Multidrug therapy in leprosy and its future components.

PMID- 7806901
TI  - Not by chemotherapy alone.

PMID- 7806902
TI  - A radically different approach for treatment of drug-resistant tuberculosis and
      leprosy.

PMID- 7806903
TI  - M Seal Grip aids for leprosy patients.

PMID- 7806904
TI  - Dapsone poisoning.

PMID- 7806905
TI  - Early onset dapsone syndrome.

PMID- 7806906
TI  - Reactions and immunization.

PMID- 7806907
TI  - Effect of xylol, urea and DPX on biological structures in leprosy cultures.

PMID- 7806908
TI  - Infected pancreatic necrosis.

PMID- 7806909
TI  - Genetic determinants of mortality in acute necrotizing pancreatitis.
AB  - Acute necrotizing pancreatitis (ANP), which often progresses to infection,
      sepsis, and multisystem organ failure, runs a course remarkably similar to that
      seen frequently after severe burns, massive physical trauma, or major surgery.
      There is extensive evidence that the development of the sepsis response is
      mediated by immunocytes, particularly activated polymorphonuclear leukocytes
      (PMNLs) and their secretions (reactive oxygen species, lysosomal hydrolases,
      cytokines, and so on). Some years ago it was suggested that the high mortality of
      ANP may be related to an overaggressive immunological defense system of the host
      rather than to autodigestion of the gland. Recent investigations of the
      immunoregulatory responses following surgery or other trauma have not only
      furnished additional support for this concept, but also revealed some genetic
      factors that may critically influence the outcome of posttraumatic illness
      including ANP. The prognostic significance of abnormal, early polymorphonuclear
      leukocyte (PMNL) activation in the development of sepsis, high neutrophil
      expression of certain receptor molecules, low monocyte and lymphocyte expression
      of major histocompatibility antigen MHC-class II, and the influence of the
      genetically encoded TNF and IL-1 secretion on the course of the illness are
      discussed and related to ANP. Evidence is presented for the potential usefulness
      of some of these parameters in the prognosis and future treatment of ANP.

PMID- 7806910
TI  - Role of fine needle aspiration cytology and endoscopic biopsy in the preoperative
      assessment of pancreatic and peripancreatic malignancies.
AB  - Sixty-seven of 207 patients with pancreatic and peripancreatic malignancies
      underwent preoperative fine needle aspiration cytology (FNA), and 24 patients
      underwent intraluminal endoscopic biopsies. All patients had confirmation of the
      diagnosis of malignancy either at operation, autopsy, or by clinical follow-up.
      FNA of liver metastases was positive for malignancy in 12 of 12 patients. FNA of
      the pancreas was performed on 44 patients with pancreatic adenocarcinoma and 11
      patients with other pancreatic or peripancreatic malignancies. The diagnosis of
      cancer was established by FNA in 32 of 44 (72.4%) patients with pancreatic
      adenocarcinoma and 1 of 11 patients (9.1%) with other pancreatic or
      peripancreatic malignancies. In the patients with pancreatic adenocarcinoma, 17
      of 18 patients (94.4%) who had no operative intervention, 12 of 18 (66.7%)
      patients who had palliative bypass procedures, and 3 of 8 (37.5%) patients
      resected had positive FNA. Eighteen of 24 patients (75%) who underwent
      intraluminal endoscopic biopsies, and 11 of 15 (73.3%) with ampullary carcinoma
      were positive. We believe that FNA is of limited value in the diagnosis of small
      resectable tumors of the pancreas as it identified cancer in only 3 of 8 patients
      in whom it was employed. False negative FNA may delay the diagnosis and treatment
      of pancreatic malignancies. Patients in whom there is a high index of suspicion
      of pancreatic or peripancreatic malignancy based on clinical presentation, CT
      scan, or ERCP assessment do not require preoperative, histologic proof of
      malignancy prior to pancreaticoduodenectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7806911
TI  - The proteolytic effect of pancreatic pseudocyst fluid on vessel walls.
AB  - The possible in vivo consequences of proteolytic activity found in pancreatic
      pseudocyst fluid was investigated experimentally using fresh vessels from rabbit
      and humans. Proteolytic pseudocyst fluid caused a pronounced and time-dependent
      decrease in breaking strength of fresh vessels. A destruction of the normal
      histological architecture and fragmentation of the elastic tissue of the vessel
      wall paralleled the mechanical findings. The proteolytic digestion was caused by
      the low-mol-wt fraction of the pseudocyst fluid, corresponding to free proteases.
      Part of this proteolysis was probably caused by pancreatic proteases, since
      pancreatic juice also caused a decrease in breaking strength and a destruction of
      the histologic architecture of the vessel wall. Proteases bound to protease
      inhibitors, i.e., to alpha-2-macroglobulin, had no proteolytic activity. It is
      concluded that the proteolytic digestion caused by proteolytic pancreatic
      pseudocyst fluid may well explain severe complications of pancreatic pseudocysts,
      like bleeding within the pseudocyst and rupture of the entire pseudocyst wall,
      although the proteolytic digestion is probably counteracted by a constant
      regeneration of the pseudocyst wall in vivo.

PMID- 7806912
TI  - Colonic proteolysis following pancreatic duct ligation in the rat.
AB  - Luminal proteolytic activity (PA) of different colonic segments was ascertained
      in animals subjected to pancreatic duct ligation (PDL) and in control rats. The
      PDL rats revealed a significant PA reduction in the cecum, proximal colon (P <
      0.01), and distal colon (P < 0.005). Proteolytic activity, trypsin, and
      chymotrypsin activity in control rats diminished progressively from the cecum to
      the distal colon. Conversely in PDL rats, we found maximal PA in distal colon.
      The conclusion is drawn that a significant proportion of colonic proteolytic
      activity can be attributed to pancreatic proteases with a maximal contribution at
      cecum level.

PMID- 7806913
TI  - Trypsinogen expression by two human pancreatic cell lines CFPAC-1 and CAPAN-1.
      Modulation during spontaneous and induced cell growth.
AB  - We previously demonstrated that two human pancreatic adenocarcinoma cell lines,
      CFPAC-1 (established from a patient with cystic fibrosis) and CAPAN-1, were able
      to secrete trypsinogens 1 and 2 specifically. In order to analyze the relation of
      trypsin secretion to differentiation and cell growth, we undertook a comparative
      study of immunoreactive trypsin 1 (IRT) secretion by the two cell lines during
      cell growth in the presence and in the absence of various differentiating agents:
      sodium butyrate (NaBut), dimethylsulfoxide (DMSO), and dexamethasone (DX). In the
      presence of NaBut, IRT levels in the supernatants of both cell lines were
      slightly increased, whereas the cellular growth of both cell lines decreased
      significantly. In the presence of DX, IRT levels in cell culture conditioned
      media immediately and dramatically decreased, but the cell growth of neither cell
      line was affected by DX. An important increase in IRT levels was observed when
      CFPAC-1 cells and CAPAN-1 cells were grown in the presence of DMSO, but for both
      cell lines the cellular growth decreased in the presence of DMSO. Our data show
      that neither the IRT secretion level nor the differentiation state of these cell
      lines correlates with cellular growth, and suggests that the expression of
      pancreatic proteases by these two tumor cell lines could be either related to a
      common stem cell with this potential or to a possible acinar origin of pancreatic
      cancer, as recently proposed by others.

PMID- 7806914
TI  - The lysosomal hydrolases in the rat pancreas after maximal or supramaximal
      stimulation with cerulein.
AB  - The decompartmentation of lysosomal compartment in pancreatic acinar cells with
      consecutive activation of zymogens might play an important role as a "trigger
      mechanism" in acute pancreatitis. The admixture of lysosomal hydrolases to
      secretory enzymes in pancreatic juice was found, but their role in pancreatic
      secretion remains obscure. The aim of the present study was to assess the
      fragility of pancreatic lysosomal structure after maximal (optimal) or
      supramaximal stimulation of rats with cerulein during 3, 6, 12 h, and after
      recovery. In the mitochondrial-lysosomal (M-L) and in the supernatant (S) of
      pancreases free (F) total (T), and fractional free (%F/T) activities of beta
      glucuronidase (beta G), acid phosphatase (AcP), cathepsins (Cs), and beta-N
      acetyl-hexosaminidase (NAH) were estimated. In edematous pancreatitis following
      supramaximal stimulation with cerulein, a significant increase of %F/T of beta G
      in whole homogenate began at 6 h of hyperstimulation in comparison to the control
      (93 vs 42% p < 0.01). This increment persisted until 12 h of hyperstimulation and
      declined after 24 and 48 h of recovery to 67-69%. The changes of %F/T of beta G
      in M-L followed those in whole homogenate, and additionally the increase free
      activity in S after 6 h of hyperstimulation and after 24 h recovery occurred. The
      respective activities of other hydrolases showed a similar pattern of changes. It
      is of interest that fragility of lysosomal membranes increases significantly also
      after maximal stimulation when inflammatory changes were absent. Our results
      suggest that the increase of lysosomal fragility of the pancreas is most unlikely
      pathological in itself, but also occurs during stimulated pancreatic
      secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7806915
TI  - Diabetes and pancreatic cancer: the egg or the hen? Abstracts of the symposium. A
      meeting of the World Congress of Gastroenterology. October 5,1994, Los Angeles,
      CA.

PMID- 7806916
TI  - Classification of pancreatic cancer staging revisited. Abstracts of the workshop.
      A meeting of the World Congress of Gastroenterology, October 5, 1994, Los
      Angeles, CA.

PMID- 7806917
TI  - Multiple field hyperthermia combined with radiotherapy in advanced carcinoma of
      the breast.
AB  - Extensive recurrences on the chest wall of advanced carcinoma of the breast in 20
      patients were treated with multiple field patchwork hyperthermia combined with
      radiation therapy between 1987-1991. The objective of the study was to evaluate
      the feasibility, tumour response and complications of treating extensive lesions
      with multiple, overlapping fields of hyperthermia. All lesions were diffuse
      encompassing up to 2900 cm2 in area with or without multiple nodules < or = 3 cm
      deep. All lesions had failed previous therapy with all but three failing previous
      radiotherapy. Hyperthermia consisted of 282 hyperthermia applicator fields and
      357 hyperthermia treatments with external 915 MHz microwaves using commercially
      available applicators. Hyperthermia applicator fields were defined by the surface
      50% SAR distribution of a particular applicator, and hyperthermia fields were
      abutted to cover the entire tumour bearing area. Radiation therapy consisted of
      81 fields to a mean dose of 40 +/- 1 Gy (SE), 88% of fields received between 30
      and 50 Gy. The equivalent dose was 42 +/- 1 Gy, based on the linear-quadratic
      model and alpha/beta = 25 (Fowler 1989). Overlapping hyperthermia fields were
      separated by an interval of at least three days. Up to four heat sessions per
      week were required to cover the entire tumour in a rotating fashion. The
      hyperthermia treatment time was 60 min. Hyperthermia treatments were continued
      for the duration of radiation therapy. Each hyperthermia applicator field was
      heated at least once. Patients were exposed to a mean of 14 +/- 3 hyperthermia
      applicator fields (range of 3-46 fields) and a mean of 18 +/- 3 hyperthermia
      treatments (range of 6-61) delivered over a mean of 7.5 +/- 0.9 weeks (range of 3
      17 weeks). Each field was heated an average of 1.3 times. The tumour complete
      response rate was 95% with a recurrence rate of 5%. Nevertheless, the mean
      survival of patients with a complete response was only 10.8 +/- 1.7 months (range
      of 2-28 months) because of the systemic tumour burden existing outside of the
      treated fields in these patients. Neither complete response, local control nor
      survival after thermoradiotherapy correlated with the disease free interval
      between initial mastectomy and recurrence. There was no evidence of increased
      thermal damage to skin nor evidence of tumour recurrence at junctions of
      hyperthermia field overlap. It is concluded that recurrent advanced carcinoma of
      the breast presenting as extensive, diffuse lesions on the chest wall can be
      treated as effectively with multiple field patchwork thermoradiotherapy as can
      nodular lesions treated with single hyperthermia fields.

PMID- 7806918
TI  - Hyperthermia (heat shock)-induced protein denaturation in liver, muscle and lens
      tissue as determined by differential scanning calorimetry.
AB  - Protein denaturation has been shown to occur in cells during heat shock and is
      closely correlated with the cellular responses to hyperthermia; however, little
      is known about protein denaturation in tissue. This study describes an analysis
      of endothermic transitions in the hyperthermic region using differential scanning
      calorimetry (DSC) in liver, white muscle, and lens tissue from Wistar rat, New
      Zealand white rabbit, and Rainbow trout. Complex DSC profiles consisting of
      several transitions were obtained for each tissue. Evidence is given that these
      transitions are due primarily to protein denaturation. Onset temperatures of
      denaturation (Tl) for rat liver, muscle, and lens are about 38, 39 and 48 degrees
      C, respectively. Thus, significant protein denaturation occurs in liver and
      muscle during mild hyperthermia (40-45 degrees C) with lens considerably more
      stable. The values of Tl for the same tissue from the different animals
      correlates well with body temperature (rabbit 39.4, rat 38.2, and trout grown at
      11 degrees C); Tl increased in the same order as the body temperature for each
      tissue. Thus, there is correlation between the onset temperature for protein
      denaturation in these tissues and body temperature.

PMID- 7806919
TI  - Local treatment of rabbit VX2 rectal carcinoma with combined hyperthermia and
      intratumoral CDDP injection.
AB  - The efficacy of combined use of hyperthermia and intratumoral cisplatin (CDDP)
      injection was investigated in rabbit rectal carcinoma models produced by VX2
      carcinoma injection. Local hyperthermia was administered with a 13.56 MHz
      radiofrequency generator at 42-43 degrees C for 30 min. CDDP (3 mg) was injected
      into two sites within tumours. Temperatures in the VX2 rectal carcinomas reached
      42-43 degrees C within 3 min following initiation of heating and remained stable.
      Tumour growth was inhibited markedly in rabbit undergoing combined treatment with
      intratumoral CDDP and hyperthermia, when compared with rabbit treated with
      hyperthermia or intratumoral CDDP alone. Histological examination further
      revealed that combined treatment resulted in more extensive tumour necrosis, when
      compared with hyperthermia or CDDP alone. Therefore, combined hyperthermia and
      CDDP intratumoral injection may be useful for neoadjuvant preoperative treatment
      of advanced rectal carcinomas as well as patients with recurrent rectal
      carcinoma.

PMID- 7806920
TI  - Effect of heat on viral protein production and budding in cultured mammalian
      cells.
AB  - The life cycle of enveloped viruses is intimately associated with, and influenced
      by, host cell membrane organization, which is altered by hyperthermia.
      Hyperthermia-modified Moloney murine leukaemia virus (M-MuLV) release, protein
      production and intracellular protein processing in a chronically infected
      cultured murine cell line, C9CL98 (C9). Both 44 degrees C/45 min and 42.8 degrees
      C/135 min substantially decreased cell-free viral env protein 8-48 h postheating,
      but virus release and cellular viral protein content increased following 42.8
      degrees C/25 min. Proteolytic processing of viral Pr65 gag precursor to p30 gag
      protein, normally observed within unheated C9 cells, was blocked for at least 8 h
      after 44 degrees C/45 min. Virus released from heated C9 cells was as infectious
      to NIH/3T3 cells as was virus from control cells. Cells surviving exposure to
      42.8 degrees C/135 min became thermotolerant to decreased virus release from a
      second heating if delivered 10-48 h after the initial heating. The mechanism by
      which virus release is blocked after hyperthermia remains to be elucidated.

PMID- 7806921
TI  - Time-temperature relationships for step-down heating in normal and thermotolerant
      cells.
AB  - Normal and thermotolerant H35 cells were submitted to step-down heating (SDH).
      SDH can significantly reduce the induction and expression of thermotolerance. For
      SDH a sensitizing treatment (ST) at 44.6 degrees C was followed by a test
      treatment (TT) at a lower hyperthermic temperature. The comparison between the
      thermotolerant and non-thermotolerant condition was based on isosurvival ST
      doses. For both conditions dose-effect relationships were obtained by plotting
      the ST-surviving fraction against the D0 of a TT. The TT was at either 41 or 42.5
      degrees C, representing respectively, a permissive or a non-permissive condition
      for chronic induction of thermotolerance (CIT). The complex dose-effect
      relationships are partly exponential. In non-thermotolerant cells tested at 42.5
      degrees C the dose-effect relationship between ST and TT is relatively weak. At
      41 degrees C, however, the expression of CIT is strongly inhibited after a ST
      that kills < 20% of the cells. At higher ST doses the response is comparable with
      that at 42.5 degrees C. In thermotolerant cells a high degree of
      thermosensitization is also observed for relatively low ST doses, but in contrast
      with non-thermotolerant cells a stronger dose-effect relationship remains at the
      higher ST doses. Ultimately this results in a comparatively higher degree of
      thermosensitization that can be achieved in non-thermotolerant cells. For
      example, at an isosurviving fraction of 0.15 the reduction of D0 is non
      thermotolerant cells at 42.5 degrees C is less than five times, whereas in
      thermotolerant cells, the D0 reduction is between 40 and 50 times. A similar
      reduction is found in non-thermotolerant cells tested at 41 degrees C.
      Subsequently, an isosurvival ST dose of about 40% was used in combination with a
      TT that was varied between 39 and 44 degrees C. D0's were plotted in an Arrhenius
      diagram to obtain a time-temperature relationship for the effect of SDH on
      thermotolerant and non-thermotolerant cells. The four plots are all biphasic with
      a downward inflection. Thermotolerance causes an upward shift of the inflection
      point of 2 degrees C relative to single-heated cells, whereas SDH causes a
      downward shift of 1 degree C in single-heated cells and of 2 degrees C in
      thermotolerant cells. For most of the temperature range, i.e. 39-43.5 degrees C,
      SDH decreases the activation energies.

PMID- 7806922
TI  - Influence of elevated body temperature on circulating immunoglobulin-secreting
      cells.
AB  - This work was designed to investigate the effect of in vivo hyperthermia in man
      on circulating immunoglobulin-secreting cells. Eight healthy male volunteers were
      immersed into a hot waterbath (WI) (water temperature 39.5 degrees C) for 2 h,
      whereby their body temperature rose to 39.5 degrees C. On another occasion they
      served as their own controls, being immersed into thermoneutral water (water
      temperature 34.5 degrees C) for 2 h. Blood samples were drawn before immersion,
      at body temperatures of 38, 39 and 39.5 degrees C, as well as 2 h after WI when
      their body temperatures were normalized. In the control experiments, blood
      samples were drawn at identical time points. A significant increase in the number
      of IgM-secreting cells per fixed number of blood mononuclear cells (BMNC)
      occurred 2 h after WI, whereas the number of IgA-secreting cells per fixed number
      of BMNC did not change. When the possible redistribution of BMNC was taken into
      account, the concentrations of IgM- and IgA-secreting cells (per ml blood)
      increased non-significantly during WI.

PMID- 7806923
TI  - On the role of hsp72 in heat-induced intranuclear protein aggregation.
AB  - Heat treatment of cells results in an increased protein content of nuclei and
      nuclear matrices when isolated after the heat treatment. This increase of TX-100
      insoluble protein is interpreted as being the result of protein denaturation and
      subsequent aggregation. After the heat treatment cells can (partly) recover from
      these aggregates. Recent data suggest that heat shock proteins (hsps) might be
      involved in the recovery (disaggregation) from these heat-induced insoluble
      protein complexes. In this report, the role of hsp72 in the process of
      aggregation and disaggregation was investigated using: non-tolerant rat-1 cells,
      thermotolerant rat-1 cells (rat-1 TT), and transfected rat-1 cells constitutively
      expressing the human inducible hsp72 gene (HR-24 cells). After heating the
      various cells, it was observed that the expression of the human hsp72 confers
      heat resistance (43-45 degrees C). Heat-induced intranuclear protein aggregation
      was less in HR and rat-1 TT cells as compared to nontolerant rat-1 cells. After
      heat treatments leading to the same initial intranuclear protein aggregation, rat
      1 TT cells recovered more rapidly from these aggregates, while HR cells recovered
      at the same rate as nontolerant rat-1 cells. Our data suggest that increased
      levels of hsp72 can confer heat resistance at the level of initial (nuclear) heat
      damage. Elevated levels of hsp72 alone, however, do not enable cells to recover
      more rapidly from heat-induced intranuclear protein aggregates.

PMID- 7806924
TI  - Feasibility of using neural networks to estimate minimum tumour temperature and
      perfusion values.
AB  - We examine the ability of neural networks to estimate the tissue perfusion values
      present and the minimum temperature in numerically calculated (Pennes, Bioheat
      Transfer Equation) steady-state hyperthermia temperature fields based on a
      limited number of measured temperatures within this field A hierarchical system
      of neural networks consisting of a first layer of pattern recognizing neural
      networks and a second layer of hypersurface reconstructing neural networks is
      shown to be capable of estimating these variables within a selected error
      tolerance. The results indicate that estimating the minimum tumour temperature
      directly with the system of neural networks may be more effective than using the
      indirect method of numerically recreating a temperature field with perfusion
      estimates and then obtaining the minimum tumour temperature from the estimated
      temperature field. Additional results indicate that if the locations of the
      measured temperatures within the temperature field are selected appropriately,
      the hierarchical system of neural networks can tolerate a moderate level of model
      mismatch. This model mismatch can come from errors in modelling the tumour
      boundaries, the sensor locations, or the magnitude of the power deposition. This
      paper is not intended to assess or demonstrate clinical applicability but to be a
      first step in investigating the feasibility of neural networks for parameter
      estimation related to hyperthermia studies.

PMID- 7806925
TI  - Effect of phase modulation on the temperature distribution of a microwave
      hyperthermia antenna array in vivo.
AB  - Perfused, canine skeletal muscle and the brain tumour of a cancer patient were
      heated with an array of four parallel, interstitial antennas placed on the
      corners of a 2-cm square and driven at 915 MHz. The temperature distributions
      along the axial and diagonal catheters were measured with equal-phase driving of
      the antennas and with several time-varying schemes of driving phase differences
      among the antennas. When equal-phase driving was replaced by a rotating scheme of
      90 degrees driving phase differences, the tissue area in the junction plane
      heated above a normalized index temperature of 0.6 increased by a factor of about
      1.25. With a rotating phase of 135 degrees, the same area increased by a factor
      of about 1.6. The axial temperature distribution was not affected significantly
      by driving phase.

PMID- 7806926
TI  - Simulation of bidirectional ultrasound hyperthermia treatments of neck tumours.
AB  - The temperature distributions produced in neck tumours by using either a single,
      scanned transducer (a unidirectional scan) or two separate transducers whose axis
      are perpendicular (a bidirectional scan) were simulated. The three-dimensional
      neck model included separate anatomical regions for the normal neck muscle
      tissue, the tumour, the spinal column and the trachea (no large blood vessels).
      The effects of variations in the transducer frequency and f number, the tumour
      size and location, and the normal and tumour blood perfusion rates were studies.
      The best simulated temperature distributions were produced by bidirectionally
      scanned, 2 MHz, f number 2.0 ultrasound transducers whose powers were modulated
      as a function of position. The simulated temperature distributions from such
      modulated bidirectional scans were significantly better than those of both
      unidirectional and unmodulated bidirectional scans. The 1-MHz transducers
      generally produced hot spots at the tissue-spine and/or tissue-trachea interface.
      The 3-MHz transducers eliminated those deep hot spots but created other hot spots
      close to the skin surface, and did not adequately heat the deeper regions of the
      tumour. These results from the simplified computer simulations may be used to
      guide the construction of improved ultrasound hyperthermia systems for the
      treatment of neck tumours.

PMID- 7806927
TI  - A variable microwave array attenuator for use with single-element waveguide
      applicators.
AB  - The effectiveness of hyperthermia treatments is often limited by temperature
      inhomogeneity that arises in the treatment field due to variable tissue
      properties and blood flow. Moreover, blood flow can change during a treatment,
      leading to the formation of hot and cool areas even if the initial temperature
      distribution is uniform. A variable microwave array attenuator has been
      constructed, that will enable the field patterns of single element microwave
      waveguide hyperthermia applicators to be altered during treatment, to improve
      temperature homogeneity. The coupling bolus was designed with an array of
      individually controlled elements, each filled with a microwave absorbing saline
      solution. Additions or withdrawals of saline are made to alter the power
      deposition in a specific area of the treatment field. Thermographic measurements
      were made in muscle equivalent phantom materials, with the bolus/waveguide
      assembly. Results showed that the variable array attenuator was able to
      significantly alter the heating pattern of a large waveguide applicator.

PMID- 7806928
TI  - Quality assurance in various radiative hyperthermia systems applying a phantom
      with LED matrix.
AB  - The Amsterdam phantom with LED-matrix is applied as an instrument in testing the
      performance of four types of radiative deep-body hyperthermia systems, which are
      in clinical use in Germany and The Netherlands. The devices tested were Essen's
      BSD-1000, Berlin's BSD-2000, Utrecht's Coaxial TEM applicator and Amsterdam's
      Four-waveguide-array. Photographs were taken of the matrix of dipoles loaded with
      light-emitting diodes (LED) to visualize the distribution of the RF power
      deposition or specific absorption rate (SAR) in the aperture midplane. The
      utility of the phantom with LED matrix for various types of radiative
      hyperthermia systems is demonstrated. Within this preliminary study, the
      influence of important parameters on the SAR-pattern in the aperture midplane was
      demonstrated. After corrections on the phase relation of the applicators a
      central focus in the SAR distribution could be realized in all systems and could
      also be moved in any direction. The patterns of the central focus changed in its
      absolute values and its proportions depending on the relative relations of phase
      and amplitude of the lateral applicators with respect to the top and bottom
      applicator. Frequency dependency was recognized for the central focus of the BSD
      1000 as well as for the irradiation pattern of a single applicator for the BSD
      2000. In the Coaxial TEM applicator it was demonstrated that the dimension of the
      open water bolus influenced the absolute value of SAR in the aperture midplane.

PMID- 7806930
TI  - [Age changes in the lumbar spine: radiological follow-up studies over more than
      ten years].
AB  - To determine the morphological changes due to aging in the lumbar spine and
      lumbar intervertebral disc, radiological follow-up studies were performed for 245
      subjects over more than 10 years. The results were as follows: 1) Disc narrowing
      increased with age and was not related to sex or occupation, 2) the occurrence
      and progression of disc narrowing were different between the upper and the lower
      lumbar discs. Severe disc degeneration was noted in the L4/5 disc. The growth of
      osteophytes in the lumbar spine was more progressive in males and in physical
      laborers but was not related to disc narrowing. Since all discs did not become
      narrow at a constant rate with aging, then disc degeneration should not be
      considered as a purely aging change, but should be regarded as partly related to
      aging. Causal factors of disc degeneration should be further investigated on
      genetic and environmental aspects in each individual case. The occurrence of
      ankylosing spinal hyperostosis (ASH, Forestier) was not related to disc
      narrowing. This study supported the concept that ASH was a different entity from
      disc narrowing although both changes sometimes occurred in combination together.

PMID- 7806929
TI  - Partial radiocarpal arthrodesis.
AB  - Eight patients underwent partial radiocarpal arthrodesis for various wrist
      disorders. There were 5 men and 3 women, whose age at operation ranged from 33 to
      59 years with an average of 44 years. The indications for operation included post
      traumatic changes secondary to distal radius fracture in 5 cases, Kienbock's
      disease in 1, Madelung's deformity in 1, and rheumatoid arthritis in 1.
      Arthrodesis was performed at the radiolunate joint in 5 cases, and at the
      radioscapholunate joint in 3 cases. In all cases, bone union was obtained within
      3 months postoperatively. Postoperative wrist pain disappeared in 6 cases, and
      decreased in 2 cases. The average postoperative flexion-extension arc of motion
      was 35 degrees in the radioscapholunate arthrodesis group, and 85 degrees in the
      radiolunate arthrodesis group. The postoperative grip strength compared with the
      unaffected hand averaged 51% in the radioscapholunate arthrodesis group, and 68%
      in the radiolunate arthrodesis group. One patient showed a deterioration in the
      osteoarthritic change in the midcarpal joint.

PMID- 7806931
TI  - [The collateral ligaments of the elbow joint: their functional anatomy with
      special reference to the pathology and treatment of post-traumatic stiff elbow].
AB  - Factors which cause stiff elbow were investigated both experimentally and
      clinically. Since a thickened and shortened medial collateral ligament is often
      seen in stiff elbow, then changes in the length of the medial collateral ligament
      (MCL) and in the length of the lateral collateral ligament (LCL) were
      investigated in cadaver elbow specimens, and correlated with the observed range
      of motion. The MCL was divided into five bundles, and the LCL into three bundles.
      The length changes during flexion and extension of the elbow joint were measured,
      and the length change pattern was found to be different from bundle to bundle.
      The lengths of the LCL and the anterior oblique ligament (AOL) of the MCL changed
      little during elbow flexion. On the other hand, the length of the posterior
      oblique ligament (POL) of the MCL considerably increased when the elbow joint was
      flexed. The more posterior the bundle was, the larger the change in length that
      was observed. Because the origin of the POL is far distant from the axis of
      motion, it was suspected that a shortening in the POL was one of the most
      important pathologic changes in stiff elbow. The results of the biomechanic study
      were applied to a subsequent clinical study. Scar formation or ectopic
      ossification on the medial and/or posterior parts of the elbow joint was observed
      in 38 of 43 cases at surgery. These pathologic regions were resected, including
      the scarred POL. The intra-operative findings revealed that the major restraints
      in stiff elbow were the medial and/or posterior parts of the elbow. The
      importance of the shortened POL in the clinical pathology of stiff elbow was
      clearly demonstrated.

PMID- 7806932
TI  - [An anatomical study of the carpal tunnel for endoscopic carpal tunnel release].
AB  - An anatomical study of the carpal tunnel was performed to characterize the
      transverse carpal ligament, enabling improved endoscopic carpal tunnel release.
      One hundred wrist joints obtained from 50 cadavers were studied. The width of the
      transverse carpal ligament (TCL) was found to be narrower in females than in
      males, and there was no significant difference in the width of the ligament
      between the right and the left wrist joints. The length of the TCL was not
      significantly different between males and females or between the right and left
      wrist joints. On the sagittal plane, the TCL was spindle-shaped and its thickest
      part was in the distal third. The thickness of the TCL had a significant negative
      correlation with age. The width of the TCL had a significant positive correlation
      with both its length (p < 0.01) and the thickness of its distal part (p < 0.01).
      Neither the distance between the distal edge of the TCL and the superficial
      palmar arch nor the distance between the radial edge of the pisiform bone and the
      ulnar artery at the distal edge of the TCL were significantly correlated with
      sex, laterality, or age. These results indicated that the width and thickness of
      the TCL and the ulnar artery can be predicted by calculating the length of the
      TCL percutaneously, thus enabling a safe and reliable endoscopic carpal tunnel
      release to be performed clinically without any complication.

PMID- 7806933
TI  - [Proteoglycan and collagen synthesis of cultured fibrochondrocytes from the human
      knee joint meniscus].
AB  - Fibrochondrocytes isolated from different parts of the human knee joint meniscus
      were cultured, and their morphology and ability to synthesize matrix components
      were investigated. The mid-portion of the medial meniscus was divided into two
      parts (the outer one-third and the inner two-thirds), and cells were obtained for
      culture by pronase and collagenase digestion. The appearance of the
      fibrochondrocytes was different in monolayer culture from that of both articular
      chondrocytes and fibroblasts. However, there was no difference between the cells
      obtained from the two different parts of the meniscus. Although proteoglycan
      synthesis by cells from the inner two-thirds was higher than that by cells from
      the outer one-third of the meniscus, there was no difference in the collagen
      synthesis. Fibrochondrocytes from the meniscus were found to synthesize cartilage
      like proteoglycan. Proteoglycan synthesis by meniscus cells and articular
      chondrocytes was stimulated by TGF-beta 1 in a dosage-dependent manner. These
      findings indicated that fibrochondrocytes possessed similar characteristics to
      articular chondrocytes in terms of proteoglycan metabolism.

PMID- 7806934
TI  - [The effects of anterior cruciate ligament resection and subsequent running
      training on muscles around the knee joint in rat].
AB  - The purpose of this study was to evaluate the effects of running training on the
      muscles in rat after resection of the anterior cruciate ligament (ACL). The
      biochemical and histochemical changes were analyzed in the muscles around the
      knee joint from which the ACL was dissected, and the rats were subsequently
      forced to undergo endurance running. After ACL resection, the wet weights of all
      muscles around the knee joint decreased but an increase was found in the number
      of slow-twitch fibers, especially in the vastus lateralis and vastus medialis
      muscles. The activities of glycolytic and oxidative enzymes in all muscles tended
      to decrease following resection. Rats which had undergone ACL resection were put
      through training in the form of appropriate endurance running, causing
      significant increases in the wet weights of all muscles, except for the vastus
      medialis, and a decrease in the number of slow-twitch fibers in the vastus
      medialis. In addition, all the enzyme activities tended to decrease following
      training. Therefore, the influences of ACL resection and subsequent running
      training were clearly demonstrated in the vastus medialis muscle. These changes
      may have been caused by joint instability and sensory reflex dysfunction by
      deafferentation from the ACL mechanoreceptor (joint-ligament receptor). To
      maintain knee muscle function, stability of the joint and restoration of the
      skeletomotor system from the ACL and the muscles around the knee joint is
      necessary.

PMID- 7806935
TI  - [Criteria for the evaluating treatment on primary bone sarcoma].
AB  - The criteria for the evaluation of the treatment on primary bone sarcoma proposed
      by the Musculoskeletal Tumor Committee of the Japanese Orthopaedic Association
      (JOA) were accepted in 1993 by the Joint Committee for Cancer Therapy of the
      Japan Society for Cancer Therapy. The responses to treatment are classified as a
      complete response (CR), a partial response (PR), no change (NC), or as
      progressive disease (PD). It is a requirement that the condition of CR, PR, or NC
      continues for at least 4 weeks. The radiographical criteria are as follows: CR,
      the disappearance of the intramedullary lesions and the bone trabeculae
      recovering a normal appearance; PR, the circumscription of the extraosseous tumor
      and an appearance of sclerotic foci within the intramedullary lesion; NC, no
      changes noted in the extraosseous and intramedullary lesions; PD, an increase in
      the extraosseous or intramedullary lesion and/or the appearance of new lesions.
      Histopathological criteria are as follows: CR, no tumor cells appearing viable in
      any of the histologic sections; PR, greater than 90% tumor necrosis attributable
      to treatment; NC, 50 to 90% tumor necrosis and other secondary changes
      attributable to treatment; PD, less than 50% tumor necrosis. Responses in the
      clinical signs and symptoms including tumor size (or circumference of the
      extremities at the site of the tumor), pain and local heat are also graded as
      follows: PR, subsiding symptoms and/or decrease in the tumor size; NC, neither
      exacerbation nor decrease in the symptoms and no change in size; PD, the
      exacerbation of symptoms or an increase in size. Additionally, the serum alkaline
      phosphatase level can be used for evaluating the effect of the treatment on the
      osteosarcoma. The extent of the response to preoperative chemotherapy is a
      powerful predictor of patient survival.

PMID- 7806936
TI  - [Origin and function of osteoclasts--morphological standpoint].

PMID- 7806937
TI  - [A role of serum albumin in dentine formation].

PMID- 7806938
TI  - [Alteration in production of vasomediators associated with in vitro aging in
      cultured human umbilical vein endothelial cells].
AB  - Differences in the secretion of some vascular regulators, endothelin-1 (ET-1),
      prostacylin (PGI2), thromboxane A2 (TXA2) and nitric oxide (NO) associated with
      in vitro aging, were investigated in cultured endothelial cells isolated from
      normal human umbilical veins (HUVECs). HUVECs from different population doubling
      levels (PDLs) were cultured in a medium MCDB-104 supplemented with FBS and ECGF.
      Cell saturation density of HUVECs decreased by 5-fold between PDL 7 and 67. PGI2
      secretion per cell increased by 6-fold, and TXA2 secretion per cell increased by
      18-fold between PDL 7 and 67. The ratio of PGI2 to TXA2 secretion decreased 3
      fold between PDL 7 and 40 and remained at the lower level between PDL 40 and 67.
      The secretion of ET-1 by HUVECs at a young stage of growth (PDL 7) increased
      linearly with time between 0 and 36 hours of incubation. ET-1 secretion per cell
      increased between PDL 7 and 67 by 5-fold after 4-hr incubation and by 3-fold
      after 9-hr incubation. The release of NO was assayed by a newly established,
      highly sensitive assay system monitoring guanosine 3':5'-cyclic monophosphate
      (cGMP) formation in a pig kidney epithelial cell line cocultured with HUVECs. The
      cGMP formation by NO released from HUVECs decreased 3.3-fold between PDL 8 and
      50. These results suggest that the vaso-constrictive activity of endothelial
      cells increases during in vitro aging which may reflect the increased vascular
      disorders in the aged people.

PMID- 7806939
TI  - [Clinical evaluation of measuring system of occlusal force].
AB  - An occlusal diagnostic system was evaluated for clinical applications. This
      system consists of pressure sensitive sheets (DENTAL PRESCALE, Fuji Photo Film
      Co.) and analyzing computer (OCCLUZER FPD703, Fuji Photo Film Co.). The clinical
      efficiency of this system was evaluated in aged dentates, aged complete denture
      wearers and an aged patient suffered from periodontitis. The results were as
      follows: 1. There was a positive correlation between the masticatory efficiency
      and maximum occlusal force. 2. In the complete denture wearers, the distances
      from the medial line to the center of the occlusal load were statistically
      greater in the adjustment needed cases than in the control group. 3. In a case of
      periodontitis, the full arch fixed splint was adjusted using this system. After
      adjustment, the maximum occlusal force and contact area increased, and the
      maximum and medial pressure of the occlusal contact force decreased. 4. It was
      suggested that this system would be available for the examination of masticatory
      efficiency and diagnosis of various types of occlusions.

PMID- 7806940
TI  - [Cell cycle arrest induced by epidermal growth factor on human squamous cell
      carcinoma cell lines].
AB  - Although human squamous cell carcinoma (SCC) cell lines frequently contain an
      elevated number of epidermal growth factor (EGF) receptor accompanied with
      amplification of EGF receptor/c-erbB gene, it is well known that EGF inhibits the
      growth of these cells in culture at doses that stimulate the growth of epidermal
      keratinocytes and dermal fibroblasts. To study this growth inhibitory effect of
      EGF on the SCC cell lines, 3H-thymidine incorporation into DNA and cell cycle
      distribution were analyzed. In HSC-1 and NA cells, which contain the highest
      number of EGF receptor among these SCC cell lines, the inhibition of 3H-thymidine
      incorporation was apparent 2 to 4 hours after treatment with 100 ng/ml of EGF and
      reached more than 95% inhibition after 24 hours. Two-color cell cycle analysis
      using fluorescein isothiocyanate (FITC)-conjugated anti-Bromodeoxyuridine (BrdU)
      antibody and propidium iodide revealed that this inhibitory effect was due to
      cell cycle arrest not only in G1 but also in G2 phase. This effect was well
      correlated to the sensitivity to the growth inhibitory effect of EGF among the 4
      SCC cell lines. These observations suggest that the SCC cells contain altered
      machineries which regulate the normal cell growth in both G1 and G2 phases, and
      the EGF affects these machineries via overexpressed its receptor.

PMID- 7806941
TI  - [Systematic diagnosis and treatment method for temporomandibular disorders--new
      chart for primary diagnosis and treatment].
AB  - In this study, the classification of temporomandibular disorders of Japanese
      Society for Temporomandibular Joint was subdivided into ten types for the purpose
      of connecting directly with treatment, then a new chart for primary diagnosis and
      treatment were expressed. Ten types, i.e. type I (masticatory muscle disorders),
      type II (micro traumatic synovitis), type IIIc- (disk disorders except internal
      derangement; open lock, eminense click and crepitus), type IIIc+ (internal
      derangement; disc anterior displacement with reduction), type III L (internal
      derangement; disc anterior displacement without reduction, type IVo
      (osteoarthrosis with no TMJ symptoms), type IVp (osteoarthrosis with TMJ pain and
      no disc disorders), type IVc- (osteoarthrosis with crepitus, eminense click and
      open lock), type IVc+ (osteoarthrosis with internal derangement; disc anterior
      displacement with reduction), type IV L (osteoarthrosis with internal
      derangement; disc anterior displacement without reduction) 605 patients who
      visited our clinic from January 1994 to June 1994 were classified by the new
      chart for primary diagnosis; type I: 37 cases, type II: 142 cases, type IIIc-:56
      cases, type III c+: 215 cases, type III L: 82 cases, type IVo: 8 cases, type IVp:
      11 cases, type IVc-: 10 cases, type IV+: 19 cases, type IVL: 25 cases.

PMID- 7806943
TI  - Tolerance and self-reactivity in V gamma 1.1C gamma 4 transgenic mice.
AB  - Immunological tolerance is the process of inhibiting or eliminating lymphocytes
      that recognize self-derived antigens. By removing potentially harmful self
      reactive clones, this mechanism allows for the random generation of a diverse
      repertoire of T-cells capable of responding to foreign pathogens. Although all
      self-reactive T-cells should be removed from the repertoire, it is quite clear
      from many recent studies that a significant fraction of T-cells bearing gamma
      delta T-cell receptors (TCR) recognize self-derived antigens in normal healthy
      mice. The presence of self-reactive T-cells in healthy animals presents a paradox
      which may be explained by understanding the transient expression of the antigens
      (e.g., MHC class Ib, Heat Shock Proteins) that have been identified for gamma
      delta T-cells thus far. Data from experiments with V gamma 1.1C gamma 4
      transgenic mice demonstrating the presence of self-reactive gamma delta T-cells
      and their influence on lymphoid development and immune surveillance will be
      examined in this review.

PMID- 7806942
TI  - Autoimmunity versus allo- and xeno-reactivity in SCID mice.
AB  - The ability of SCID mice to accept xenografts has been exploited to study the
      survival, function and potential of peripheral blood mononuclear cells (PBMC)
      from patients with autoimmune disorders to produce tissue injury in the mouse.
      Studies performed with PBMC obtained from patients with organ specific and
      multisystem autoimmune diseases indicate that human PBMC survive in SCID mice for
      several months, produce IgG and autoantibodies with the same specificities as are
      found in the donor. Tissue injury is not generally observed in the SCID mouse
      recipient. SCID mice have also been partially reconstituted with bone marrow from
      BB (diabetic) and MRL (lupus) mice. SCID mice injected with both spleen cells
      from mice with collagen induced arthritis together with native bovine collagen
      developed more severe arthritis than the donors. SCID mice have therefore proven
      to be a useful resource to study autoimmunity. In both xeno- and allografts of
      mature lymphocytes, graft versus host reactions occur. Further studies will be
      necessary to improve donor cell survival without aggravating graft versus host
      disease.

PMID- 7806944
TI  - Autoimmunity and tolerance in Ig-transgenic mice: murine SLE as a model to study
      B cell tolerance.

PMID- 7806945
TI  - ECG of the month. Yogi-ism. Complete AV block.

PMID- 7806946
TI  - Tonsillectomy and adenoidectomy in children: current indications.
AB  - The indications for tonsillectomy have undergone considerable refinement in
      recent years. In patients that fail to respond to conservative medical management
      for tonsil and adenoid disorders in children, surgical management often yields
      excellent results.

PMID- 7806947
TI  - Clinical applications of the interleukins: present and future.
AB  - Clinical use of biologic agents, especially in the fields of hematology and
      oncology, is becoming increasingly common. Many agents, interferon-alpha,
      interferon-gamma, granulocyte and granulocyte-monocyte colony stimulating
      factors, erythropoietin, and interleukin-2 have already been approved for
      clinical use. Others are currently in clinical trials or will soon be available
      for administration to humans. This review summarizes the properties of
      interleukins 1 through 12, their derivation, activities, and approved or
      potential clinical uses.

PMID- 7806948
TI  - The Journal 100 years ago. November 1844/94.

PMID- 7806949
TI  - Tubal ectopic pregnancy: a histologic, morphometric, and statistical study.
AB  - Pathologists are occasionally asked for medicolegal reasons to estimate the
      gestational age of an ectopic pregnancy based on morphologic findings. We
      evaluated the correlation between the gestational age and the maximal diameter of
      the resected fallopian tube, the average diameter of chorionic villi, the number
      of chorionic villi per square millimeter of the microscopic section, the number
      of degenerated villi per square millimeter, the number of syncytial knots per
      square millimeter, and the average number of layers of cytotrophoblastic cells
      covering the villi. There was a significant correlation between the diameter of
      the fallopian tube and the gestational age, with a correlation coefficient of
      0.41 and a P value of .05. There was no significant correlation of the
      gestational age with any of the microscopic parameters measured. The findings
      indicate that an approximate estimation of the gestational age of tubal ectopic
      pregnancies may be made using the diameter of the resected fallopian tube.

PMID- 7806950
TI  - Core biopsy of breast lesions.
AB  - In patients with mammographically detected breast lesions, stereotactic-guided
      core biopsy was studied as an alternative to surgical biopsy. Fifty-two patients
      with a total of 58 mammographically detected suspicious lesions underwent
      stereotactic-guided core biopsy (average 4.7 cores per lesion) with a 14-G biopsy
      gun. The results were correlated with subsequent needle-localized surgical biopsy
      that was performed immediately after the core specimens were obtained. The core
      biopsy results correlated with the surgical biopsy in 54 of the 58 lesions (93%
      agreement), including correct identification of 14 malignancies. No false
      negative or false positive results occurred using core biopsy to detect cancer.
      These findings suggest stereotactic-guided core biopsy is an accurate method and
      an acceptable alternative to needle localization in the diagnosis of
      mammographically suspicious nonpalpable breast lesions.

PMID- 7806951
TI  - Practice parameters--boon or bane?

PMID- 7806952
TI  - Newborn hearing screening.
AB  - Congenital deafness is a relatively common problem with an incidence of 1/300 to
      1/1000. Most states have no mass screening program for hearing loss, but the
      state of Kentucky compiles a High Risk Registry which is a historical survey of
      parents relating to risk factors for hearing loss. Unfortunately this survey can
      miss 50% of those who have a hearing deficit. If not detected prior to discharge,
      there is often a delay in diagnosis of deafness which prevents early
      intervention. We report 2 years' experience at Kosair Children's Hospital where
      1,987 infants admitted to well baby, intermediate, or intensive care nurseries
      were screened using the ALGO-1 screener (Natus Medical Inc, Foster City, CA)
      which is a modified auditory brain stem evoked response (ABR). Our screening of
      this population led to an 11% incidence of referral for complete audiological
      evaluation. There were no significant complications. Forty-eight infants were
      found to have nonspecified, sensorineural, or conductive hearing loss. The
      positive predictive value of the test was 96%. Therefore, we feel that the use of
      the modified ABR in the newborn is a timely, cost efficient method of screening
      for hearing loss and should be used for mass screening of all newborns.

PMID- 7806953
TI  - Acute miliary blastomycosis in an AIDS patient.
AB  - The incidence of blastomycosis in immunocompromised patients with HIV infection
      is very low when compared to other mycoses. Of the 19 cases of blastomycosis
      described in HIV-infected patients, only four had a miliary pattern on chest x
      ray. A case of acute miliary blastomycosis in an HIV infected patient from
      Louisville is described.

PMID- 7806954
TI  - Northern exposure: a look at the Canadian health care system.

PMID- 7806955
TI  - Epidemic of litigation.

PMID- 7806956
TI  - Homework and students with learning disabilities and behavior disorders: a
      practical, parent-based approach.
AB  - This article provides a limited review of the effects of homework on students
      with disabilities, the essentials of effective homework programs, and variables
      that affect home-school partnerships. The emphasis is on students with learning
      disabilities and behavior disorders who are at risk for academic failure and poor
      school adjustment. The authors introduce the University of Utah Homework Partners
      series, which highlights three homework packages: a cooperative learning teams
      based approach for classrooms, a package to train parents to be positive academic
      tutors for their children, and a systematic program to train parents in effective
      homework practices. The latter package is the major focus of this article because
      it emphasizes home-school partnerships for students with disabilities. Sanity
      Savers for Parents: Tips for Tackling Homework is a training program that teaches
      parents how to assess, design, and troubleshoot an effective in-home homework
      program for their child. The overall emphasis of this program is on practical
      interventions that are positive and motivating and include a home-to-school link
      to maximize the generalization of effects for students with learning and behavior
      disabilities.

PMID- 7806957
TI  - Making homework work at home: the parent's perspective.
AB  - This article views homework through the eyes of parents in a rural area whose
      children with disabilities spent a majority of their time in general education
      classrooms. The qualitative analysis of data from individual interviews, focus
      groups, and parent action research logs yielded five themes: (a) Parents felt ill
      prepared to help their children with homework; (b) parents wanted more
      information about the classroom teachers' expectations of their child and of
      their roles as parents in helping with homework; (c) parents wanted their
      children to be given individualized homework assignments; (d) parents valued
      hands-on homework and projects in which the whole family could participate; and
      (e) parents wanted a two-way communication system that would allow them to become
      partners on their child's instructional team.

PMID- 7806958
TI  - Schoolwork, homework, life's work: the experience of students with and without
      learning disabilities.
AB  - Elementary school students were interviewed about schoolwork, homework, and
      personal learning projects (e.g., learning about astronomy). Four groups of
      students were distinguished. Those in the first group experienced school
      knowledge as an integral part of life and inseparable from their personal
      projects; students in the second group saw such knowledge as necessary for
      preparing for life, but as less engaging than their personal projects. For those
      in the third group, schoolwork was an imposition, contrasting sharply with
      satisfying personal learning projects. Those in the fourth group lacked absorbing
      personal learning projects and found schoolwork to be an imposition. Students
      with learning disabilities (more than students without) fell into the last
      category. Fostering more favorable motivation and voice (ability to articulate
      purposes and critique schooling) in such students might involve changing their
      views of school knowledge, helping them find personal identity-building learning
      projects, and reducing the dichotomy between schoolwork and personal projects.

PMID- 7806959
TI  - Practical recommendations for using homework with students with learning
      disabilities.
AB  - Homework is a commonly used school practice. Its importance for students with
      learning disabilities has increased in recent years as these students have spent
      more instructional time in inclusive settings where homework is regularly given
      and as educational reforms have influenced the amount of homework being given.
      The first part of the article reviews selected issues that relate to using
      homework with students who have been identified as learning disabled. The major
      part of the article highlights effective (i.e., empirically validated) and
      recommended (i.e., suggested in the literature or determined by field-based
      reports) practices for using homework with this population.

PMID- 7806960
TI  - Inclusion: time for a change--a response to Margaret N. Carr.

PMID- 7806961
TI  - The advantages of inclusion for students with learning disabilities.

PMID- 7806962
TI  - Preference for visual scanning strategies versus phonological rehearsal in
      university students with reading disabilities.
AB  - This study investigated strategic preferences for visual scanning versus
      phonological rehearsal for recognizing words, pronounceable letter strings, and
      symbol strings by university students with reading disabilities (RD). Forty-seven
      subjects participated in this study: 20 students with reading disabilities who
      reported current difficulties in reading, as well as problems in learning to read
      at an early age; 15 students with learning disabilities (LD) who reported current
      difficulties in learning in areas other than reading but did not recall
      difficulties in learning to read; and 12 nondisabled readers (NR). The main
      dependent measures were response latency on a matching task for words, nonwords,
      and symbol strings, and posttest verbal reports of strategies used. Results
      showed that (a) most subjects in the NR group consistently used a strategy of
      phonological rehearsal for both words and nonwords, whereas most subjects with RD
      consistently used a strategy of visual scanning for these tasks, and (b) the NR
      group responded significantly faster than did the RD and LD groups to all three
      types of stimuli. The results indicate differences between university students
      who have a reading disability and nondisabled readers in strategic preferences
      for processing phonological information, with a clear preference by the former
      for using visual scanning rather than phonological rehearsal in matching tasks of
      words and nonwords.

PMID- 7806963
TI  - Teaching multiplication facts to students with learning disabilities: teacher
      selected versus student-selected material prompts within the delay procedure.
AB  - This study evaluated the effectiveness of the constant time delay procedure,
      while comparing the efficiency of using teacher-selected and student-selected
      material prompts, in teaching multiplication facts to 4 male students with
      learning disabilities ranging in age from 9 years 6 months to 13 years 10 months.
      The two prompting strategies were compared in the context of a multiple-probe
      design across groups of multiplication facts, in which the sequence of strategies
      was counterbalanced across students. Results indicated that although the constant
      time delay procedure used with material prompts was effective, instruction was
      more efficient when students were allowed to select the material prompt.

PMID- 7806964
TI  - The social adjustment and self-concept of adults with learning disabilities.
AB  - This study examined the social adjustment and self-concept of 81 adults (18 to 26
      years of age), 40 of whom received special education services under the "learning
      disabilities" designation and 41 of whom had regular education programming.
      Subjects were mailed a set of questionnaires about their current functioning,
      including the Social Adjustment Scale-Self Report and the Tennessee Self-Concept
      Scale. Archival data on IQ and achievement test scores were also obtained.
      Results indicated no significant differences between groups on the social
      adjustment measure or any of its subscales, or on the measure of self-concept. A
      small subset of subjects in the learning disabilities group had clinically low
      self-concept scores. Achievement and IQ measures, collectively, were good
      predictors of global social adjustment (R2 = 96%). Overall, the findings suggest
      that this cohort of subjects with learning disabilities educated under the
      auspices of P.L. 94-142 fare about as well as their nondisabled peers in terms of
      social adjustment and self-concept. It appears that any negative effects of a
      disability classification abate once individuals leave the public school
      environment, and that previous forecasts of the socioemotional status of adults
      with learning disabilities may be unnecessarily pessimistic.

PMID- 7806965
TI  - Lipoprotein lipase and hepatic lipase: the role of asparagine-linked
      glycosylation in the expression of a functional enzyme.
AB  - Lipoprotein lipase (LPL) and hepatic lipase (HL) share two conserved asparagine
      linked glycosylation sites, located at the amino- and carboxy-terminal domains of
      the protein. Human HL contains two additional sites, preceding each conserved
      site by 36 and 35 amino acids, respectively. The utilization of these sites for
      glycan-binding and the role of each glycan chain for the catalytic function of
      human LPL, rat HL, and human HL was investigated. To accomplish this aim,
      potential Asn glycosylation sites were changed to Gln by site-directed
      mutagenesis and the resulting constructs were expressed in a mammalian (COS) cell
      system. We demonstrate the following. 1) All potential glycosylation sites in
      human LPL, rat HL, and human HL are utilized. 2) Lack of glycosylation at the two
      non-conserved sites in human HL has no effect on enzyme expression. 3)
      Glycosylation at the conserved Asn sites in the N-terminal domain of LPL and HL
      is required for the synthesis of a fully active and secreted lipase. While this
      is an absolute requirement for LPL, a portion (approximately 25%) of HL molecules
      lacking glycosylation at this essential site still becomes active and secreted.
      However, the simultaneous elimination of both glycosylation sites at the N
      terminal domain of human HL results in the virtual abolishment of enzymatic
      activity and secretion. 4) Glycosylation at the conserved sites in the C-terminal
      domain is not essential for the expression of active lipases. 5) Eliminating all
      glycosylation sites in LPL and HL results in the synthesis of inactive enzymes
      that are retained intracellularly; however, a small portion (2%) of
      unglycosylated rat HL was active and secreted. We conclude that glycosylation
      overall plays an important role in the formation of functional LPL and HL.

PMID- 7806966
TI  - The ansamycins: hypolipidemic agents stimulating cholesterol removal by
      nonclassical mechanisms.
AB  - The ansamycins CGP 43371 and CGS 24565 are derivatives of the antibiotic
      rifamycin that reduce plasma cholesterol levels in both primate and nonprimate
      species. In vivo, a striking accumulation of macrophage cholesteryl ester was
      seen in ansamycin-treated rats and hamsters, but carbon clearance studies and
      reticuloendothelial system blockade by gadolinium chloride indicated that
      phagocytosis was not involved. Simple addition of an ansamycin to macrophages or
      monocytes in vitro failed to stimulate radiolabeled lipoprotein cholesteryl ester
      association or mass accumulation. In contrast to mononuclear cells, however, the
      ansamycins did enhance radiolabeled lipoprotein cholesteryl ester association by
      liver cells in vitro. Primary hepatocyte cultures prepared from rats treated with
      radiolabeled CGP 43371 secreted CGP 43371 over an 18-h period in a fraction
      floating at d < 1.02 g/ml after density gradient ultracentrifugation that was
      relatively enriched in apoA-I. The medium containing this secreted [14C]GP 43371
      labeled lipoprotein was capable of enhancing the cholesteryl ester content of
      macrophages in vitro, suggesting that ansamycin-induced liver modification of
      lipoproteins might be involved. These drugs may serve as valuable tools for
      studying mechanisms of lipoprotein uptake.

PMID- 7806967
TI  - Hormonal regulation of hormone-sensitive lipase activity and mRNA levels in
      isolated rat adipocytes.
AB  - Hormone-sensitive lipase (HSL) mediates the lipolysis of triacylglycerol from
      mammalian adipocytes, resulting in the release of non-esterified fatty acids and
      glycerol. Although numerous studies have examined the hormonal regulation of HSL,
      the measurement of HSL mRNA levels in response to hormonal regulators has not
      been studied. This study was designed to determine the effects of epinephrine,
      growth hormone, glucagon, and dexamethasone on HSL expression by measuring HSL
      mRNA levels and glycerol release in primary cultures of rat adipocytes. Exposure
      of adipocytes to epinephrine at 10(-7) M and 10(-5) M for 4 h resulted in an
      increase in medium glycerol (209 +/- 46%, and 284 +/- 58% of control, P < 0.001,
      respectively). However, no change in HSL mRNA levels occurred due to the
      epinephrine treatment. Similarly, the peptides glucagon (10(-7) M and 10(-5) M
      for 4 h) and growth hormone (100 ng/ml for 24 h) resulted in increased medium
      glycerol and had no effect on HSL mRNA levels in adipocytes. Dexamethasone was
      added to adipocyte cultures for 4 and 24 h, and resulted in a dose-dependent
      increase of medium glycerol (102 +/- 8%, 138 +/- 8% (P < 0.001), and 168 +/- 24%
      (P < 0.001) for 10(-8) M, 10(-7) M, and 10(-6) M, respectively).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7806968
TI  - Expression of lipoprotein lipase in rat muscle: regulation by feeding and
      hypothyroidism.
AB  - Lipoprotein lipase (LPL) is a key enzyme in lipid metabolism and is found
      predominantly in adipose tissue and muscle. We examined the mechanism of
      regulation of LPL in muscles composed of different fiber types (soleus, extensor
      digitorum longus, and heart) in fed, fasted, and hypothyroid rats. In all
      muscles, the detergent-extractable (EXT) fraction represented approximately 95%
      of total LPL activity and mass. LPL activity was similar in the heparin
      releasable (HR) fractions of heart and soleus (predominantly type I fibers),
      while in the EXT fraction LPL activity in soleus was 418 +/- 48 nEq/min per g,
      and in heart was 272 +/- 30 nEq/min per g (P < 0.05). However, LPL activity in
      extensor digitorum longus (EDL, predominantly type II fibers) was considerably
      lower (7.9 +/- 0.8 nEq/min per g in EXT, P < 0.0001 versus heart and soleus). LPL
      immunoreactive mass followed a pattern similar to LPL activity. LPL mRNA levels
      were quantitated by both Northern blotting and reverse transcriptase-polymerase
      chain reaction (RT-PCR), and were approximately equal in heart and soleus, and 5
      fold lower in EDL. In response to feeding, LPL activity, mass, and mRNA levels in
      heart were 30% to 50% lower than in fasted rat heart, although feeding had no
      effect on soleus or EDL. In hypothyroid animals, muscle LPL activity was
      increased by 3- to 4-fold in the HR (but not EXT) fractions of heart and soleus
      (P < 0.05), with no change in LPL mass or mRNA. Thus, muscles with oxidative,
      type I fibers expressed higher levels of LPL mRNA than muscles containing
      glycolytic, type II fibers.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7806969
TI  - A novel missense mutation in the C-terminal domain of lipoprotein lipase (Glu410-
      >Val) leads to enzyme inactivation and familial chylomicronemia.
AB  - Lipoprotein lipase (LPL) is a complex enzyme consisting of multiple functional
      domains essential for the initial hydrolysis of triglycerides present in plasma
      lipoproteins. Previous studies have localized the catalytic domain of LPL,
      responsible for the hydrolytic function of the enzyme, to the N-terminus whereas
      the C-terminal end may play a role in lipid and heparin binding. To date, most
      described missense mutations resulting in a nonfunctional LPL have been located
      in the N-terminal region of the enzyme. In this manuscript we describe the defect
      in the LPL gene of a patient with triglycerides ranging from normal to 12,000
      mg/dl, low LPL mass, and no LPL activity in post-heparin plasma. Sequencing of
      patient PCR-amplified DNA identified two separate mutations in the C-terminal
      domain of LPL: an A-->T transversion at nucleotide 1484 resulting in a Glu410-
      >Val substitution and a C-->G mutation at position 1595 that introduces a
      premature stop codon at position 447. Digestion with MaeIII and MnII established
      that the patient is a true homozygote for both mutations. In order to investigate
      the functional significance of these defects, mutant enzymes containing either
      the Val410 or the Ter447 mutations as well as both Val410 and Ter447, were
      expressed in vitro. Compared to the wild-type enzyme, LPL447 demonstrated a
      moderate reduction of specific activity using triolein (70% of normal) and
      tributyrin (74% of normal) substrates, while LPL410 had a significant (11% and
      23% of normal) reduction of the normal lipase and esterase specific activities,
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7806970
TI  - Effect of phospholipase C and apolipophorin III on the structure and stability of
      lipophorin subspecies.
AB  - Four distinct subspecies of the insect hemolymph lipoprotein, lipophorin, that
      range in diacylglycerol (DAG) content from approximately 100 to 1000 molecules
      per particle, were treated with phospholipase C. Lipid analysis demonstrated that
      both phosphatidylcholine and phosphatidylethanolamine were hydrolyzed to DAG.
      Phospholipase C was used to remove 74-82% of the phospholipid of different
      lipophorins and these were analyzed for aggregation. Low density lipophorin
      (LDLp), the largest subspecies, with a diameter of approximately 23 nm, developed
      turbidity (monitored by sample absorbance at 340 nm) suggesting the formation of
      lipoprotein aggregates. High density lipophorin-adult (HDLp-A) and high density
      lipophorin-wanderer 1 (HDLp-W1) also displayed an increase in A340 when incubated
      with phospholipase C, although the maximal increase observed was considerably
      less than that for LDLp on a per particle basis. Phospholipase C caused only a
      minimal increase in A340 in a fourth subspecies, high density lipophorin-wanderer
      2 (HDLp-W2), which contains an even lower amount of DAG. Electron microscopy was
      used to evaluate changes in particle morphology as a result of phospholipid
      depletion. HDLp-W2 and HDLp-W1 showed signs of progressive aggregation and
      particle fusion. A similar aggregation/fusion was seen in the case of high
      density lipophorin adult (HDLp-A) while LDLp samples contained multiple
      aggregation/fusion foci and resultant very large particles. In the presence of
      exogenous apolipophorin III (apoLp-III), phospholipase C-induced lipophorin
      aggregation/fusion was prevented. Electron microscopy of LDLp and HDLp-A samples
      revealed that apoLp-III-stabilized, phospholipase C-treated particles had a
      morphology similar to that of control particles.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7806971
TI  - Predominance of esterified hydroperoxy-linoleic acid in human monocyte-oxidized
      LDL.
AB  - Low density lipoprotein that was oxidized by activated human monocytes was
      analyzed to determine the identity of oxidized fatty acids present and the
      conditions required for their formation. The oxidized lipids were also analyzed
      under conditions allowing preservation of their oxidation state. Using reversed
      phase high performance liquid chromatography (HPLC) analysis of native and
      saponified lipid extracts of oxidized low density lipoprotein (LDL), we found
      that the major fatty acid oxidation product was esterified
      hydroperoxyoctadecadienoic acid (HPODE), the oxidized product of the most
      abundant polyunsaturated fatty acid in human LDL, linoleic acid. Although some
      esterified hydroxyoctadecadienoic acid (HODE) was also detected, the reduction of
      HPODE to HODE did not appear to be monocyte-dependent. Essentially all of the
      HPODE was found to be esterified with the majority being esterified to
      cholesterol followed by phospholipids and generally following the abundance of
      esterified linoleic acid within the lipid classes. The percent of cholesteryl
      linoleate converted to cholesteryl HPODE and cholesteryl HODE at the end of the
      24-h incubation was determined to be approximately 13.5%. The formation of
      oxidized esterified linoleic acid in the LDL was shown to require immunological
      activation of the human monocytes, a previously observed requirement for general
      LDL oxidation in this culture system. The oxidized esterified linoleic acid was
      present in the supernatant with the LDL and was not cell-associated. HPODE
      formation on LDL was prevented by including superoxide dismutase (SOD) or
      eicosatetraynoic acid (ETYA) during the 24-h coincubation of activated monocytes
      with LDL whereas indomethacin was without effect. The analysis of the lipid
      oxidation products in oxidized LDL can provide insight into the mechanisms
      involved in oxidation of LDL by activated human monocytes.

PMID- 7806972
TI  - Postprandial lipemia differentially influences high density lipoprotein
      subpopulations LpAI and LpAI,AII.
AB  - The behavior of apolipoprotein-defined subpopulations LpAI and LpAI,AII within
      high density lipoprotein (HDL) subclasses 2 and 3 was analyzed in the
      postprandial phase after a fat load. For the whole group of subjects, increases
      in plasma concentrations of HDL, principally due to the influx of lipoprotein
      surface components, were largely confined to the HDL3 density range and involved
      LpAI,AII and LpAI. However, the degree of postprandial lipemia influenced the
      distribution of surface remnants between the subfractions. In subjects with a
      limited postprandial rise in triglycerides, increased HDL mass was predominantly
      associated with LpAI,AII, and equally distributed between HDL2 and HDL3.
      Conversely, subjects with exaggerated postprandial lipemia manifested increased
      mass primarily within the HDL3 density range, implicating both LpAI,AII and LpAI.
      Stepwise regression analysis identified a two-variable model, involving LpAI,AII
      within HDL2 and LpAI within HDL3, as best defining the relationship between
      postprandial lipemia and the increase in HDL mass. Postprandial increases in
      triglyceride content were observed for all HDL subfractions, whilst modifications
      to the core lipid mass ratios were significant only for LpAI,AII. Stepwise
      regression analysis revealed a significant correlation between postprandial
      lipemia and the increase in triglyceride concentration only of LpAI,AII within
      HDL3. The results suggest that postprandial lipemia differentially influences
      apolipoprotein-defined HDL subfractions. The extent of postprandial lipemia may
      determine the involvement of different HDL subfractions in postprandial
      lipoprotein metabolism.

PMID- 7806973
TI  - Human plasma LDL cryopreserved with sucrose maintains in vivo kinetics
      indistinguishable from freshly isolated human LDL in cynomolgus monkeys.
AB  - We previously reported that freeze-thawing of LDL causes marked alterations in
      its structure and in vitro biological behavior, and that such changes can be
      completely abolished by the addition of sucrose to the LDL solution prior to
      freezing. (Rumsey, S. C. et al., J. Lipid Res. 1992. 33: 1551-1561). We now
      questioned whether the cryopreservative action of sucrose would be equally
      effective in maintaining the in vivo metabolic characteristics of LDL. Two dual
      label LDL turnover studies were performed in cynomolgus monkeys (n = 8) comparing
      freshly isolated human LDL with human LDL that was frozen in sucrose (10% w/v)
      for a short (20 h) or long period (6 months). The same sucrose-cryopreserved LDL
      was used for both the short- and long-term studies; different fresh LDL
      preparations were used in each study. Absorption spectrophotometry, gel
      filtration, and electron microscopy of LDL samples frozen with sucrose showed no
      evidence of physical alterations or aggregation, and there was no evidence of
      very rapid clearance of cryopreserved LDL from monkey plasma after injection.
      Fractional catabolic rates (FCR) of fresh and frozen LDL were very similar in
      either the short-term or long-term experiments: 2.09 +/- 0.86 versus 2.16 +/-
      0.88, short-term and 3.03 +/- 2.28 versus 3.08 +/- 2.29, long-term (pools per
      day; mean +/- SD). The difference between FCR of fresh and frozen LDL for each
      animal averaged -0.076 +/- 0.074 and 0.01 +/- 0.22 (mean +/- SD), for short-term
      and long-term freezing, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7806974
TI  - Positions of conjugation of bile acids with glucose and N-acetylglucosamine in
      vitro.
AB  - In order to establish the position of conjugation of bile acids with glucose or N
      acetylglucosamine, glucosides of chenodeoxycholic and hyodeoxycholic acids and of
      13C-labeled cholic, lithocholic, chenodeoxycholic, hyodeoxycholic, and
      ursodeoxycholic acids, and N-acetylglucosaminides of ursodeoxycholic,
      isoursodeoxycholic, 3-dehydro-ursodeoxycholic, and ursodeoxycholylglycine were
      synthesized in vitro. The conjugates were purified by anion-exchange
      chromatography and reversed-phase HLPC and were analyzed by gas chromatography
      mass spectrometry. The glucosides of chenodeoxycholic and hyodeoxycholic acids
      were also analyzed after periodate and chronic acid oxidation. All conjugates
      were analyzed by fast atom bombardment mass spectrometry with collision-induced
      dissociation. Glucose conjugation was shown to occur at C-3 in all bile acid
      glucosides studied. In contrast, the selective N-acetylglucosaminidation of 7
      beta-hydroxy bile acids was shown to occur at the 7 beta-position.

PMID- 7806975
TI  - Abnormalities of glycosphingolipid, sulfatide, and ceramide in the polycystic
      (cpk/cpk) mouse.
AB  - Polycystic kidney disease is a disorder marked by aberrant renal tubular
      epithelial cell proliferation and transport abnormalities. Sphingolipids are
      ubiquitous membrane components implicated in several cellular functions including
      cell membrane sorting, signaling, growth, ion transport, and adhesion. To
      investigate a potential pathogenic role for sphingolipids in cystic kidney
      disease, we studied the sphingolipid content and associated enzymatic activities
      of the kidneys from cpk/cpk mice and their phenotypically normal litter mates.
      The neutral glycolipids, including glucosylceramide and lactosylceramide,
      displayed a striking increase in 3-week-old cpk/cpk mice as did the acidic lipid,
      ganglioside GM3. However, a correspondingly significant decrease in
      sulfoglycolipid and ceramide concentration was observed in the cpk/cpk kidneys.
      Glucosylceramide synthase activity was higher in the kidneys of the cpk/cpk mice
      than in those of the controls. Kinetic analysis of the glucosylceramide synthase
      revealed the presence of an endogenous activator in the cystic kidney. A marked
      decrease in sulfotransferase activity was observed in both whole kidney
      homogenates and in microsomal preparations that was consistent with the decrement
      in sulfolipid content. The increase in GM3, glucosyl- and lactosylceramide may
      therefore be the result of impaired sulfolipid synthesis at the 3-week time
      point. While sulfolipid and glucosylceramide concentrations are not different at
      1 and 2 weeks of age, ceramide concentrations in cystic kidneys are significantly
      reduced compared to kidneys from phenotypically normal mice. These results
      suggest that sphingolipids may play a potential role in the proliferative and
      transport abnormalities associated with cystic renal disease and the development
      of azotemia.

PMID- 7806976
TI  - Age-related, sex-related, and seasonal changes of plasma lipoprotein
      concentrations in trout.
AB  - Seasonal variability in physiological parameters can be attributed to seasonal
      variations in environmental factors and/or to the consequence of the presence of
      endogenous circannual rhythms. In the current study we have measured plasma
      levels of lipids and of the different lipoprotein classes in fasting trout
      (Oncorhynchus mykiss) between the ages of 5 and 44 months. Independent of age and
      sexual maturity, a circannual variation in the low density lipoprotein
      concentration between 250 and 1300 mg/dl was demonstrated in both sexes. These
      seasonal fluctuations might be controlled by an endogenous biological clock
      synchronized by the photoperiod. The lipoprotein profile of trout is dominated by
      high density lipoproteins as early as the first months of life. Their
      concentration increases progressively during sexual maturation from about 1200
      mg/dl in juveniles to about 2500 mg/dl during spermiation or at the moment of
      ovulation. This increase is highly significantly correlated with the increased
      concentration of testosterone occurring in both sexes during sexual maturation.
      The concentration of very low density lipoproteins increases substantially, from
      about 150 mg/dl to a maximal concentration of 800 mg/dl in females and 1100 mg/dl
      in males, during the deposit phase of lipid reserves which precedes the rapid
      increase in the gonadosomatic ratio. In the course of rapid ovarian growth,
      vitellogenin appears in the plasma of females and reaches a concentration of 2200
      mg/dl 1 month before ovulation. From these results it is concluded that season
      and reproductive cycle are the two main factors affecting basal plasma lipid and
      lipoprotein levels in trout. Environmental factors such as photoperiod or
      endocrine factors such as the concentration of steroid hormones can be correlated
      and/or involved in the regulation of these quantitative variations. These results
      also suggest the presence of an endogenous biological clock able to exert an
      independent effect on plasma lipid and lipoprotein levels.

PMID- 7806977
TI  - Inhibition of cholesteryl ester transfer protein in normocholesterolemic and
      hypercholesterolemic hamsters: effects on HDL subspecies, quantity, and
      apolipoprotein distribution.
AB  - The effects of cholesteryl ester transfer protein (CETP) inhibition on the serum
      lipoprotein profile in both normocholesterolemic and hypercholesterolemic
      hamsters has been determined following subcutaneous injection of 12.5 mg/kg of
      the CETP neutralizing monoclonal antibody, TP2. Inhibition of CETP activity was
      greater than 60% and resulted in a 30-40% increase in high density lipoprotein
      (HDL) in both normal and hypercholesterolemic animals. These HDL effects were
      observed 1 day post-injection, were maximal by 4 days, and returned to control
      values by 14 days. Inhibition of CETP activity resulted in a decrease in both low
      density lipoprotein (LDL) and very low density lipoprotein (VLDL) cholesterol
      concomitant with HDL increase, and in hypercholesterolemic animals resulted in
      increased total serum cholesterol. In addition to the quantitative differences in
      LDL and HDL, there were significant increases in the size of the HDL, a shift to
      smaller LDL particles, and changes in apolipoprotein (apo) composition as
      evaluated by FPLC and Western blot analysis. Large apoA-I-poor and apoE
      containing HDL became prevalent in hypercholesterolemic hamsters after CETP
      inhibition. In addition, the size of the CETP-containing HDL particles increased
      with inhibition of transfer activity. While these effects were apparent in
      normocholesterolemic animals, the changes in apolipoprotein distribution and HDL
      subspecies as detected on native gels were more significant in the
      hypercholesterolemic animals. The changes in the HDL profile and apolipoprotein
      distribution after CETP inhibition in hamsters were similar to those reported in
      CETP-deficient Japanese subjects, suggesting the utility of the
      hypercholesterolemic hamster as an in vivo model for the understanding of the
      lipoprotein changes associated with CETP inhibition.

PMID- 7806978
TI  - Bile salts of the toad, Bufo marinus: characterization of a new unsaturated
      higher bile acid, 3 alpha,7 alpha,12 alpha,26-tetrahydroxy-5 beta-cholest-23-en
      27-oic acid.
AB  - The bile salts present in gallbladder bile of the toad, Bufo marinus, were found
      to consist of a mixture of bile alcohol sulfates and unconjugated bile acids. The
      major bile alcohol was 5 beta-bufol; 5 alpha- and 5 beta-cholestane-3 alpha,7
      alpha,12 alpha, 26-tetrols occurred as the minor bile alcohols. Bile acids of
      Bufo marinus were cholic acid, allocholic acid, 3 alpha,7 alpha,12 alpha
      trihydroxy-5 alpha- and 5 beta-cholestan-26-oic acids, 3 alpha,7 alpha,12 alpha
      trihydroxy-5 alpha- and 5 beta-cholest-23-en-26-oic acids, 3 alpha,7 alpha,12
      alpha, 26-tetrahydroxy-5 beta-cholestan-27-oic acid, and a C27 bile acid which
      has not been previously described. By chromatographic behavior, mass spectral
      data, and identification of the products of catalytic hydrogenation and
      ozonolysis, the structure of the new higher bile acid was elucidated as 3 alpha,7
      alpha,12 alpha,26-tetrahydroxy-5 beta-cholest-23-en-27-oic acid. The bile salt
      pattern of Bufo marinus closely resembles that of Bufo vulgaris formosus, except
      for the absence of 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholest-22-ene-24
      carboxylic acid, the major bile acid of the latter toad.

PMID- 7806979
TI  - Purification and properties of a phosphorylatable triacylglycerol lipase from the
      fat body of an insect, Manduca sexta.
AB  - A triacylglycerol lipase, presumably the first enzyme involved in the
      mobilization of lipid from the insect fat body, has been purified to homogeneity
      from the fat body of Manduca sexta. The purification procedure involved
      polyethyleneglycol precipitation, and chromatography on DEAE-cellulose, phenyl
      Sepharose, Q-Sepharose and hydroxylapatite. The final product, a protein with an
      M(r) = 76,000 by SDS-PAGE, was purified nearly 8000-fold from the original
      homogenate in a yield of about 11%. The enzyme catalyzed the hydrolysis of tri-,
      di-, and mono-oleoylglycerols, but showed highest affinity for tri- or
      dioleoylglycerol. Thus, under initial reaction conditions, the end products of
      trioleoylglycerol hydrolysis were: free fatty acids (66%), sn-2
      monooleoylglycerol (24%), sn-1,2(2,3)-dioleoylglycerol (7%), and glycerol (3%).
      The fat body lipase exhibited a preference for hydrolyzing the primary ester
      bonds of acylglycerols, and did not show stereoselectivity toward either the sn-1
      or sn-3 position of trioleoylglycerol. The enzyme had a pH optimum of 7.9, and
      was inhibited by diisopropylfluorophosphate, ATP, ADP, Mg2+, and NaF. The enzyme
      showed a strong tendency to aggregate, but was stable in detergent solutions at
      high concentration of glycerol. The polypeptide was phosphorylated by the cAMP
      dependent protein kinase from bovine heart; however, phosphorylation did not
      cause activation of the enzyme. It is suggested that this fat body lipase could
      be analogous to the "hormone-sensitive lipase" of vertebrate adipose tissue.

PMID- 7806980
TI  - Trans-9-octadecenoic acid is biologically neutral and does not regulate the low
      density lipoprotein receptor as the cis isomer does in the hamster.
AB  - The concentration of cholesterol carried in low density lipoproteins (LDL-C) is
      primarily determined by the rate at which LDL-C is produced (Jt) and the rate at
      which the liver takes up this particle through receptor-dependent transport (Jm).
      The accumulation of specific dietary fatty acids in the liver profoundly alters
      these kinetic parameters and will either increase hepatic receptor activity or
      further suppress Jm, depending upon the particular fatty acid that enriches the
      various lipid pools. This study tests the thesis that the cellular effects of
      each fatty acid are determined by the ability of that lipid to act as an
      effective substrate for cholesteryl ester formation by examining the metabolic
      effects of either cis-9-octadecenoic acid (18:1(9c)), the preferred substrate for
      esterification, or trans-9-octadecenoic acid (18:1(9t)), a poor substrate for
      this reaction. When fed to hamsters for 30 days, the steady-state concentration
      of cholesteryl esters was markedly increased by the 18:1(9c), as compared to the
      18:1(9t), compound. In animals receiving the 18:1(9c) fatty acid, hepatic
      receptor activity was significantly increased, LDL-C production was suppressed,
      and the steady-state LDL-C concentration was reduced. In contrast, the 18:1(9t)
      fatty acid did not significantly alter Jm, Jt, or the plasma LDL-C level from
      those values found in the control animals fed an isocaloric amount of a
      biologically neutral fatty acid, octanoic acid. Despite these different effects
      on the parameters of LDL metabolism, neither the cis nor trans fatty acid altered
      net cholesterol delivery to the liver from de novo sterol synthesis in any tissue
      in the body or from uptake of dietary cholesterol across the intestine.
      Therefore, these studies provide strong support for the thesis that fatty acids
      exert regulatory effects on hepatic LDL receptor activity by altering the
      distribution of cholesterol in the hepatocyte between a putative regulatory pool
      and the inert pool of cholesteryl esters. The direction and magnitude of the
      effects of specific fatty acids on receptor-dependent LDL transport appear to
      relate directly to the capacity of specific fatty acids to either promote or
      inhibit cholesteryl ester formation.

PMID- 7806981
TI  - Cellular binding site and membrane binding proteins for triglyceride-rich
      lipoproteins in human monocyte-macrophages and THP-1 monocytic cells.
AB  - Triglyceride- and cholesterol-rich foam cells derived from monocyte-macrophages
      are commonly associated with some forms of hypertriglyceridemia. In this report,
      direct binding studies at 4 degrees C demonstrate that human monocyte-macrophages
      (HMM) 1-6 days after isolation from blood and human THP-1 monocytic cells, before
      and up to 7 days after differentiation with phorbol ester, exhibit a high
      affinity (Kd 3-6 nM), saturable, specific, and apolipoprotein (apo) E-independent
      binding site for the uptake and degradation of certain triglyceride-rich
      lipoproteins (TGRLP). Ligand blotting analysis identified two membrane binding
      proteins (MBP) of apparent molecular weights of 200 and 235 kDa (MBP 200 and MBP
      235) in both cell types that share the same ligand specificity as the cellular
      site and bind hypertriglyceridemic (HTG) VLDL, trypsinized VLDL devoid of apoE
      (tryp-VLDL), and dietary plasma chylomicrons from normal subjects but not LDL,
      acetyl LDL, or normal VLDL with high affinity. Neither lipoprotein lipase nor
      apoE are required for TGRLP binding to the cells or the isolated MBPs. The
      cellular binding site and the MBPs are expressed at similar levels at all stages
      of differentiation, unlike the LDL or the acetyl LDL receptor. TGRLP that bind to
      the MBPs induce rapid, saturable, cellular triglyceride accumulation in monocytes
      as well as macrophages; normal VLDL does not. In addition, the cellular high
      affinity binding site and MBP 200 and 235 are not affected by the media sterol
      content, unlike the LDL receptor. Taken together, these data indicate that human
      monocyte-macrophages exhibit a high affinity, saturable, specific, apoE- and
      lipoprotein lipase-independent binding site and membrane binding proteins for
      TGRLP that differ in expression, specificity, and molecular size from receptors
      of the LDL receptor gene family or the acetyl LDL receptor. The shared
      characteristics of the cellular binding site with MBP 200 and MBP 235 suggest
      that they are candidates for the receptor-mediated, apoE-independent uptake of
      HTG-VLDL and chylomicrons by monocytes and macrophages and therefore may be
      involved in foam cell formation.

PMID- 7806982
TI  - Analysis of high density lipoproteins by a modified gradient gel electrophoresis
      method.
AB  - A high resolution electrophoretic method has been developed to separate plasma
      high density lipoprotein (HDL) particles by size using 4-30% polyacrylamide
      agarose (PAA) gradient gels, Sudan black B staining, and laser densitometry.
      Fourteen distinct HDL bands were observed with HDL-1 being designated as the
      largest particle and HDL-14 as the smallest particle. HDL-1 was similar in size
      to ferritin (Stokes diameter 12.2 nm), HDL-8 to catalase (9.2 nm), and HDL-13 to
      lactate dehydrogenase (8.1 nm). HDL-1 to HDL-7 were found within the density
      range of HDL2b (d 1.063-1.10 g/ml), HDL-8 to HDL-10 within HDL2a (d 1.10-1.125
      g/ml), and HDL-11 to HDL-14 within HDL3 (d 1.125-1.21 g/ml). On immunoblotting,
      apolipoprotein A-I (apoA-I) was found in all HDL bands examined, being most
      prominent in HDL-6, 11, and 12. ApoA-II was not detected in HDL bands 1-5, but
      was present in all other HDL bands and was most prominent in HDL-9. ApoE was
      detected mainly in HDL bands 1-7, and was observed in only trace amounts in other
      bands. Lp A-I isolated by immunoaffinity column chromatography from the plasma of
      five subjects contained five subspecies (HDL-5, 6, and 11-13), while Lp A-I/A-II
      also had five subspecies (HDL-8, 9, and 11-13) in these subjects. In normal
      subjects (n = 57) four or five HDL bands were generally observed, with HDL-9, 11,
      and 12 being the most frequently observed. Mean HDL particle score (method of
      sizing based on scanning densitometry, where low score indicates large size and
      high score indicates small size) was significantly correlated (P < 0.001) with
      the concentrations of HDL cholesterol (r = -0.796), HDL free cholesterol (r = 
      0.780), HDL cholesteryl ester (r = -0.683), HDL phospholipid (r = -0.663), HDL
      apoA-I (r = -0.577), and HDL protein (r = -0.459), but not with HDL triglyceride
      (r = 0.069). In addition, HDL particle score was significantly correlated (P <
      0.05) with HDL total mass (r = -0.649), HDL free cholesterol content (% of total
      mass, r = -0.608), HDL triglyceride content (r = 0.415), HDL phospholipid content
      (r = -0.359), and HDL protein content (r = 0.295), but not with HDL cholesteryl
      ester content (r = -0.219) or HDL apoA-I content (r = 0.183).(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 7806983
TI  - Health care: what are the new rules?

PMID- 7806984
TI  - Medicaid privileges.

PMID- 7806985
TI  - The demise of private practice.

PMID- 7806986
TI  - Vandals at the gates of medicine. At the crossroads of health system reform.

PMID- 7806987
TI  - A humanist looks at the mind/body connection.

PMID- 7806988
TI  - A lesson in humanism: one doctor's experience.

PMID- 7806989
TI  - Mercy death: dying by choice and not by chance.

PMID- 7806990
TI  - Caveat emptor: a response to Daniel Maguire.

PMID- 7806991
TI  - Fiftieth anniversary of the Blalock shunt.

PMID- 7806992
TI  - Expanding scale, increasing risk: population as an environmental issue.

PMID- 7806993
TI  - An overview of cutaneous malignant melanoma.
AB  - Cutaneous melanomas are an increasingly frequent lesion. Many new cases are
      diagnosed early, and simple surgical excision is often curative. Treatment may
      consist of excisional biopsy with conservative surgical margins. Prophylactic
      lymph node dissection remains controversial. The final verdict may be obtained at
      the conclusion of a large on-going multi-institutional American prospective trial
      comparing observation and prophylactic lymph node dissection. Though only a small
      number of patients present with advanced primary melanoma, future investigation
      in the treatment of disseminated disease and in understanding the tumor biology
      must continue as current chemotherapeutic and immunotherapeutic regimens show
      marginal benefit. As melanomas continue to become more prevalent, patient and
      physician education aimed at early detection and prevention should be advocated.

PMID- 7806994
TI  - The silent PPO scam.

PMID- 7806995
TI  - The "assignment of benefits" road--no longer a one-way street.

PMID- 7806996
TI  - Autoantibodies against adhesion molecules and structures in blistering skin
      diseases.

PMID- 7806997
TI  - Loss of surface immunoglobulin expression precedes B cell death by apoptosis in
      the bursa of Fabricius.
AB  - The vast majority of lymphocytes generated daily in the chicken bursa of
      Fabricius do not emigrate to the periphery but die in situ. Apoptotic cells in
      the bursa can be readily detected by the presence of fragmented DNA and by the
      large numbers of condensed cellular nuclei observed by electron microscopy.
      Consequently, most newly generated lymphocytes die by programmed cell death. We
      show that bursal cells divide rapidly and apoptotic cells are derived from
      rapidly dividing precursors. Analysis of the phenotype of bursal cells undergoing
      apoptosis demonstrated that cell death does not occur in the most mature bursal
      cell population and is therefore not random. High levels of surface Ig are
      expressed on bursal cells entering S phase of the cell cycle. In contrast, bursal
      cells in the early stages of apoptosis in vivo express very low to undetectable
      levels of surface Ig but were unequivocally confirmed as being of the B lineage
      by polymerase chain reaction (PCR) detection of rearranged Ig genes. Bursal cells
      induced to undergo apoptosis in vitro express high levels of surface Ig
      demonstrating that induction of apoptosis does not in itself induce a loss of
      surface Ig expression. Consequently, loss of surface Ig expression precedes
      bursal cell death by apoptosis in vivo, suggesting that maintenance of a
      threshold level of surface Ig may be a requirement for the continued progression
      of chicken B lymphocyte development in the bursa.

PMID- 7806998
TI  - Purification and characterization of a human membrane protein that activates the
      alternative complement pathway and allows the deposition of homologous complement
      C3.
AB  - A human myeloid cell subline, P39+, is found to be a target for human complement
      (C) via the alternative pathway and to allow the deposition of multiple C3
      fragments on its membranes, though expressing the complement regulatory proteins
      decay-accelerating factor and membrane cofactor protein. The parent cell line,
      P39-, which is phenotypically similar to the P39+ subline, does not allow the
      deposition of homologous C3 fragments. In this study, we established a monoclonal
      antibody, M161 Ab, which reacted with P39+ but not P39- cells. This Ab recognized
      a 43-kD protein in P39+ cell lysate transblotted onto nitrocellulose. Using this
      Ab as a probe, we purified the 43-kD protein, namely, M161 antigen (Ag). M161 Ag
      had a basic isoelectric point (pI), 9.3-9.4 by chromatofocusing, and was
      precipitated as an insoluble material at the pI point. The purified M161 Ag was a
      single-chain protein and did not possess N- or O-linked carbohydrates. When the
      purified M161 Ag was transblotted onto nitrocellulose and incubated with Mg(2+)
      EGTA serum, human C3 fragments were efficiently deposited on M161 Ag. The major
      species of the deposited C3 fragments was C3b. Furthermore, the C3 fragments
      bound to the M161 Ag were detached by 1 M hydroxylamine, suggesting that a
      covalent ester linkage sustains M161 Ag-C3b interaction. NH2-terminal amino acid
      analysis revealed that M161Ag is a novel membrane protein. Hence, it appeared
      that M161 Ag is a potent activator of human alternative complement pathway on
      human cells that activates homologous C3 and allows the deposition of C3b on
      itself. Thus, under some conditions, homeostasis of complement is maintained even
      on human cells, not only by the complement regulatory proteins, but also by
      membrane C3-activating molecules on which C3b is deposited.

PMID- 7806999
TI  - Activation-induced apoptosis in human macrophages: developmental regulation of a
      novel cell death pathway by macrophage colony-stimulating factor and interferon
      gamma.
AB  - Activated macrophages (M phi s) are important participants in host defense, but
      their uncontrolled activation leads rapidly to septic shock and death. One
      mechanism for regulating other dangerous cells in the immune system is programmed
      cell death, or apoptosis. Monocytes are known to undergo spontaneous apoptosis
      upon leaving the circulation unless provided with specific survival signals, but
      mature tissue M phi s are more robust cells, and it was not clear that they could
      be similarly regulated by apoptosis. We now show that during differentiation
      monocytes rapidly lose their sensitivity to apoptosis triggered by passive
      cytokine withdrawal, but they may retain a novel pathway which initiates
      apoptosis after activation with specific stimuli (zymosan and phorbol esters).
      Sensitivity to activation-induced apoptosis was developmentally determined, being
      downregulated by the maturation-promoting cytokine macrophage colony-stimulating
      factor but stably upregulated by even transient exposure to the proinflammatory
      cytokine interferon gamma (IFN-gamma). Apoptosis began within 2-4 h of
      activation, occurred in > 95% of susceptible cells, and in mixed cocultures
      selectively affected only those M phi s with a history of IFN-gamma priming.
      Consistent with a possible role for protein kinase C in the signaling pathway
      leading to cell death, the kinase inhibitor staurosporine was protective against
      both phorbol ester- and zymosan-induced apoptosis. Our studies describe a novel
      form of activation-induced M phi apoptosis which is developmentally regulated by
      two physiologically relevant cytokines. We speculate that apoptosis may serve to
      restrict the destructive potential of inflammatory M phi s.

PMID- 7807000
TI  - Molecular mechanisms that control expression of the B lymphocyte antigen receptor
      complex.
AB  - The B cell receptor for antigen (BCR) is a complex of membrane immunoglobulin
      (mIg) and at least two other proteins, Ig alpha (mb-1) and Ig beta (B29). This
      complex promotes surface expression of the BCR and acts to transduce an
      activation signal. We have used a system of mu heavy chain constructs transfected
      into murine B cell lines to probe structure-function relationships in the BCR
      complex. One mutant mu chain, in which two polar transmembrane residues (Tyr587,
      Ser588) are replaced with valine, fails to associate with Ig alpha and Ig beta
      and is incapable of transducing signals as a result of mIg cross-linking. This
      mutant is expressed on the surface at high levels when transfected into a
      plasmacytoma line that lacks Ig alpha, whereas wild-type mu is retained in this
      cell line in the endoplasmic reticulum. Pulse-chase and immunoprecipitation
      analyses indicate that the mutant is more rapidly released from calnexin than the
      wild-type mu. Further, transfection of Ig alpha into this Ig alpha-negative cell
      line allows release of the mu chain from calnexin and surface expression of the
      BCR. These results identify the transmembrane residues of mu heavy chain that
      control binding to calnexin and Ig alpha, and suggest that calnexin-dependent
      intracellular retention is an important control mechanism for expression of the
      BCR complex.

PMID- 7807001
TI  - Autoantibodies to desmoplakin I and II in patients with erythema multiforme.
AB  - Erythema multiforme (EM) represents a syndrome of chronic recurrent inflammatory
      skin disease. Depending on the severity and extent of skin and mucosal
      involvement, it is defined either as EM minor or EM major. In this study we
      demonstrate the presence of autoantibodies (aAbs) against desmoplakin I and II,
      two major proteins of the desmosomal plaque, in six of six patients with the
      severe variant of EM, EM major. Light microscopic studies of lesional skin and
      mucous membranes localized in vivo bound immunoglobulin G (IgG) in a dotted
      desmosomal pattern along the cytoplasmic membranes of keratinocytes. By
      immunoelectronmicroscopy, in vivo bound IgG was confined to the desmosomal
      plaques. These findings were confirmed by indirect immunolocalization studies
      that demonstrated the presence of IgG aAbs in the serum of patients during active
      disease. These aAbs did not only bind to desmosomal plaques of epithelial cells
      where they colocalized with defined murine monoclonal antibodies directed against
      desmoplakin I and II, but also labeled the intercalated discs of myocardial
      cells. Biochemical characterization of circulating IgG aAbs revealed desmoplakin
      I and II as actual target autoantigens. By passive transfer of serum into newborn
      mice, in vivo binding of serum aAbs to keratinocytes was shown. The findings
      presented in this study imply a humoral immune response in certain patients with
      EM major and indicate a potential pathogenetic role of aAbs against desmoplakin I
      and II in this disease.

PMID- 7807003
TI  - Transient perturbation of endothelial integrity induced by natural antibodies and
      complement.
AB  - The barrier function of blood vessels is though to be regulated at least in part
      by endothelium. This concept is supported by the dramatic loss of barrier
      function occurring in the hyperacute rejection of vascularized grafts mediated by
      anti-endothelial cell (EC) antibodies and complement. In this process, the
      endothelium is not destroyed but instead loses the ability to retain blood cells
      and plasma proteins within capillaries. The noncytotoxic mechanism that allows
      this change in EC function has been unknown. Here we report that within 10 to 20
      min of exposure to human xenoreactive natural antibodies and complement, porcine
      EC undergo alterations in cell shape and in the cytoskeleton that disrupt
      monolayer integrity and lead to formation of intercellular gaps. Gap formation is
      not associated with cell death but requires the complement complex C5b67. The
      gaps induced by anti-EC antibodies and complement are transient; gap closure
      requires formation of C5b-9 complexes on the cells and the rate of recovery
      depends on the release of cellular products into the medium. Preincubation of EC
      with dibutyryl cAMP (0.5 mM) prevents gap formation and disruption of the
      cytoskeleton caused by antibodies and complement. These results provide evidence
      that the integrity of endothelium is regulated by components of the complement
      system and suggest a mechanism that may explain the prominent loss of endothelial
      integrity seen in humoral immune responses.

PMID- 7807002
TI  - Characterization of an interleukin 4 (IL-4) responsive region in the
      immunoglobulin heavy chain germline epsilon promoter: regulation by NF-IL-4, a
      C/EBP family member and NF-kappa B/p50.
AB  - A large body of data indicate that antibody class switching is directed by
      cytokines by inducing or repressing transcription from unrearranged, or germline,
      CH genes. Interleukin 4 (IL-4) induces transcription of the germline C epsilon
      genes in activated B cells and subsequently, cells in this population will
      undergo switch recombination to immunoglobulin E. Furthermore, the data suggest
      that transcription of germline C epsilon genes is required for class switching.
      In this paper we define DNA elements required for induction of transcription of
      the germline C epsilon genes by IL-4. To do this, segments of DNA from the 5'
      flank of the initiation sites for germline epsilon RNA were ligated to a
      luciferase reporter gene and transfected into two mouse B cell lines, one of
      which can be induced to switch to IgE. By analysis of a series of 5' deletion
      constructs and linker-scanning mutations, we demonstrate that a 46-bp segment
      (residing at -126/-79 relative to the first RNA initiation site) contains an IL-4
      responsive region. By electrophoretic mobility shift assays, we find that this
      segment binds three transcription factors: the recently described NF-IL4, one or
      more members of the C/EBP family of transcription factors, and NF-kappa B/p50.
      Mutation of any of the binding sites for these three factors abolishes or reduces
      IL-4 inducibility of the epsilon promoter. A 27-bp segment within this IL-4
      response region containing binding sites for NF-IL4 and a C/EBP factor is
      sufficient to transfer IL-4 inducibility to a minimal c-fos promoter.

PMID- 7807004
TI  - Vaccination against Lyme disease caused by diverse Borrelia burgdorferi.
AB  - Diversity and mutations in the genes for outer surface proteins (Osps) A and B of
      Borrelia burgdorferi sensu lato (B. burgdorferi), the spirochetal agent of Lyme
      disease, suggests that a monovalent OspA or OspB vaccine may not provide
      protection against antigenically variable naturally occurring B. burgdorferi. We
      now show that OspA or OspB immunizations protect mice from tick-borne infection
      with heterogeneous B. burgdorferi from different geographic regions. This result
      is in distinct contrast to in vitro killing analyses and in vivo protection
      studies using syringe injections of B. burgdorferi as the challenge inoculum.
      Evaluations of vaccine efficacy against Lyme disease and other vector-borne
      infections should use the natural mode of transmission and not be predicated on
      classification systems or assays that do not rely upon the vector to transmit
      infection.

PMID- 7807005
TI  - The requirement for DM in class II-restricted antigen presentation and SDS-stable
      dimer formation is allele and species dependent.
AB  - Recently several cell lines have been identified with mutations in a major
      histocompatibility complex (MHC)-linked protein that lead to defects in class II
      restricted antigen presentation and a defect in the formation of class II SDS
      stable dimers. The defect in these cells has recently been shown to result from
      the inability to express the MHC-encoded nonclassical class II molecule called
      DM. To further examine the role of DM in class II-restricted antigen
      presentation, we asked if this defect would equally affect different allelic and
      species variants of class II molecules. To investigate this, we transfected the
      parent cell lines T1 and 8.1.6 and their respective antigen presentation mutants
      T2 and 9.5.3 with the genes encoding I-Ad and examined the derived transfectants
      for their ability to present antigen, the conformation of I-Ad at the cell
      surface, association of I-Ad with invariant chain (Ii), and the ability to form I
      Ad SDS-stable dimers. The lack of functional DM expression did not affect any of
      the anti-I-Ad monoclonal antibody (mAb) epitopes tested or the ability of I-Ad to
      associate and dissociate with Ii. Surprisingly, these studies also revealed that
      the antigen presentation defect observed for DR in the 9.5.3 cells did not
      compromise I-Ad-restricted antigen presentation. In addition, we found that the
      level of SDS-stable dimer formation did not correlate with antigen presentation
      capacity for I-Ad and that the amount of SDS-stable I-Ad dimer depends on the
      cellular context in which the class II molecule is expressed. Our results suggest
      that the ability to form SDS-stable dimer is not strictly correlated with class
      II-restricted antigen presentation. Finally, when two allelic forms of murine
      class II molecules were compared in the defective T2 cell line, it was found that
      I-Ak but not I-Ad forms SDS-stable dimers equivalent to that seen in the parental
      cell lines. Overall, our results suggest that DM may modulate rather than play a
      requisite role in I-Ad-restricted antigen presentation and SDS-stable dimer
      formation and that dependency on DM may be allele or species specific.

PMID- 7807006
TI  - Characterization of the Mycobacterium tuberculosis phagosome and evidence that
      phagosomal maturation is inhibited.
AB  - We have used the cryosection immunogold technique to study the composition of the
      Mycobacterium tuberculosis phagosome. We have used quantitative immunogold
      staining to determine the distribution of several known markers of the endosomal
      lysosomal pathway in human monocytes after ingestion of either M. tuberculosis,
      Legionella pneumophila, or polystyrene beads. Compared with the other phagocytic
      particles studied, the M. tuberculosis phagosome exhibits delayed clearance of
      major histocompatibility complex (MHC) class I molecules, relatively intense
      staining for MHC class II molecules and the endosomal marker transferrin
      receptor, and relatively weak staining for the lysosomal membrane glycoproteins,
      CD63, LAMP-1, and LAMP-2 and the lysosomal acid protease, cathepsin D. In
      contrast to M. tuberculosis, the L. pneumophila phagosome rapidly clears MHC
      class I molecules and excludes all endosomal-lysosomal markers studied. In
      contrast to both live M. tuberculosis and L. pneumophila phagosomes, phagosomes
      containing either polystyrene beads or heat-killed M. tuberculosis stain
      intensely for lysosomal membrane glycoproteins and cathepsin D. These findings
      suggest that (a) M. tuberculosis retards the maturation of its phagosome along
      the endosomal-lysosomal pathway and resides in a compartment with endosomal, as
      opposed to lysosomal, characteristics; and (b) the intraphagosomal pathway, i.e.,
      the pathway followed by several intracellular parasites that inhibit phagosome
      lysosome fusion, is heterogeneous.

PMID- 7807007
TI  - Altering the antibody repertoire via transgene homologous recombination: evidence
      for global and clone-autonomous regulation of antigen-driven B cell
      differentiation.
AB  - Antibody VH transgenes containing small amounts of natural 5' and 3' flanking DNA
      undergo nonreciprocal homologous recombination with the endogenous Igh locus in B
      cells. The resulting "hybrid" heavy chain loci are generated at a low frequency
      but are fully functional, undergoing somatic hypermutation and isotype class
      switching. We have used this recombination pathway to introduce a somatically
      mutated variable (V) region with an unusually high affinity for the hapten p
      azophenylarsonate (Ars) into the preimmune antibody repertoire. The affinity of
      this V region for Ars is 100-fold higher than any unmutated anti-Ars antibody
      previously characterized. Expression of the transgene-encoded V region did not
      affect many aspects of antigen-driven B cell differentiation, including somatic
      hypermutation, in either Ars-specific transgene- or endogenous V gene-expressing
      clones. Thus, the regulation of these processes appears to operate in a "global"
      fashion, in that the mechanisms involved are imperceptive of the relative
      affinities for antigen of the antibodies expressed by B cell clones participating
      in the immune response. In contrast, the selection of V region mutants leading to
      affinity maturation and memory cell formation was found to be strongly influenced
      by the transgenic V region, but only in clones expressing this V region.
      Hybridomas derived from transgene- and endogenous V region-expressing memory
      cells were isolated at similar frequencies from individual transgenic mice. The V
      regions expressed by hybridomas in both of these groups had 2- to 30-fold greater
      affinity for Ars than their unmutated precursors, despite the fact that the
      transgene-encoded precursors had 100-fold higher affinity than their endogenous
      counterparts. These results show that the criterion for entry into the memory
      compartment is established not by the affinity of a B cell's V region relative to
      all other V regions expressed during the response, but by the affinity of this V
      region relative to its unmutated precursor. Thus, the development of B cell
      memory is regulated in a "clone-autonomous" fashion.

PMID- 7807008
TI  - Immune pressure selects for Plasmodium falciparum parasites presenting distinct
      red blood cell surface antigens and inducing strain-specific protection in
      Saimiri sciureus monkeys.
AB  - The passive transfer of specific antibodies to a naive splenectomized Saimiri
      sciureus monkey infected with the Palo Alto FUP/SP strain of Plasmodium
      falciparum resulted in the emergence of parasites resistant to the transferred
      antibodies. Molecular typing indicated that the original and resistant parasites
      were isogenic. Saimiri monkeys primed with original parasites were fully
      susceptible to a challenge by the resistant ones, and vice versa. This absence of
      crossprotection indicates that strain-specific determinants would be the major
      targets of protective immunity developed in these monkeys. Phenotypic analysis
      showed that the surface of the infected red blood cells differed in both lines.
      Original parasites formed rosettes, autoagglutinated, presented characteristic
      knobs at the surface of the infected red blood cell, and did not agglutinate in
      the presence of a pool of human immune sera. In contrast, the resistant parasites
      did not form rosettes, did not spontaneously autoagglutinate, presented abnormal
      flattened knobs, and formed large aggregates in the presence of a pool of human
      immune sera. The presence of strain-specific determinants at the surface of the
      resistant parasites was confirmed by surface immunofluorescence and agglutination
      using homologous Saimiri serum. Neither the original nor the resistant parasites
      cytoadhered to an amelanotic melanoma cell line, suggesting that cytoadherence
      and agglutination can be dissociated. These results indicate that parasites that
      differ by the antigens exposed at the surface of the red blood cell induce strain
      specific immunity. Furthermore they show that rosetting and nonrosetting
      parasites differ in their antigenic properties and do not crossprotect.

PMID- 7807009
TI  - Expression of the herpes simplex virus type 2 latency-associated transcript
      enhances spontaneous reactivation of genital herpes in latently infected guinea
      pigs.
AB  - The latency-associated transcript (LAT) is the only herpes simplex virus (HSV)
      gene product detectable in latently infected humans and animals. In this report,
      we show that a 624-bp deletion in the promoter of the HSV-2 LAT had no
      discernable effect on viral growth in tissue culture or in acute genital
      infection of guinea pigs, but impaired LAT accumulation and led to a marked
      decrease in spontaneous genital recurrences when compared with the behavior of
      wild-type and rescuant strains. Differences in the ability of the mutant to
      replicate, or in how readily it established or maintained latency did not account
      for this finding. Thus, HSV LAT expression facilitates the spontaneous
      reactivation of latent virus.

PMID- 7807010
TI  - Genetic requirement for Ras in the transformation of fibroblasts and
      hematopoietic cells by the Bcr-Abl oncogene.
AB  - To determine the functional importance of Ras in transformation by Abl oncogenes,
      we used a genetic approach to measure the effect of impaired Ras activity on the
      ability of Bcr-Abl or v-Abl to transform cells. Expression of the catalytic
      domain of the GTPase activating protein for Ras (Gap C terminus) impaired soft
      agar colony formation by fibroblasts expressing v-Abl or Bcr-Abl by 70-80%. To
      test Ras function in a model that more closely resembles clinical diseases
      involving Bcr-Abl, double gene retroviruses expressing Bcr-Abl paired with the
      Gap C terminus or dominant negative Ras were introduced into naive mouse bone
      marrow cells. Transformation by Bcr-Abl was completely blocked in both
      situations. Coexpression of normal c-H-Ras accelerated the transforming activity
      of Bcr-Abl. These findings show that Ras activation is essential for the
      leukemogenic activity of Abl oncogenes in two distinct model systems. The results
      genetically define a connection between the Bcr-Abl cytoplasmic tyrosine kinase
      and Ras and add to the accumulating evidence that deregulation of Ras is a
      central event in the genesis of a number of molecularly distinct forms of human
      myeloid leukemia.

PMID- 7807011
TI  - Modulation of cell adhesion by changes in alpha L beta 2 (LFA-1, CD11a/CD18)
      cytoplasmic domain/cytoskeleton interaction.
AB  - The integrin alpha L beta 2 (leukocyte function-associated molecule 1,
      CD11a/CD18) mediates activation-dependent adhesion of leukocytes. The cytoplasmic
      domains of alpha L beta 2 have been demonstrated to modulate adhesiveness of
      alpha L beta 2. Affinity changes of alpha L beta 2 for its ligand or postreceptor
      events can be responsible for this modulation of adhesiveness. To investigate the
      possible role of the alpha L beta 2 cytoplasmic domains in postreceptor events we
      constructed cDNA encoding chimeric proteins with intracellular alpha L beta 2
      domains, which are responsible for alpha L beta 2 specific intracellular
      interactions, and extracellular alpha IIIb beta 3 (GP IIb/IIIa) domains, which
      allow the assessment of the receptor affinity state. The cDNA was stably
      transfected in Chinese hamster ovary cells and chimeric heterodimer formation
      proven by immunoprecipitations and flow cytometry. The chimeric receptors mediate
      adhesion to immobilized fibrinogen, and this adhesion is increased by phorbol
      myristate acetate and abolished by cytochalasin D. However, neither treatment
      affects the affinity state of the chimeric receptor, suggesting involvement of
      the cytoskeleton in the regulation of alpha L beta 2 mediated cell adhesion. To
      exclude the possibility of postoccupancy affinity changes of the chimeric
      receptors, we locked the receptors into a high affinity state by creating a
      deletion variant. The region deleted (VGFFK) is highly conserved in integrin
      alpha subunit cytoplasmic domains. Cotransfection of this deletion variant with a
      beta subunit truncation (beta 3 delta 724) and a triple mutation at 758-760 (TTT
      to AAA) of beta 2 abolishes adhesion without changing the affinity state. A
      single mutation (TTT to TAT) reduces adhesion by half without affinity change.
      Scanning electron microscopy reveals impaired spreading of these
      truncated/mutated chimeras. Immunofluorescence microscopy demonstrates a
      correlation between impaired adhesion and a decrease in the ability to form focal
      adhesions and to organize the cytoskeleton into stress fibers. These results
      describe the integrin/cytoskeleton interaction, the organization of the
      cytoskeleton, and cell spreading as postreceptor events modulating alpha L beta 2
      cytoplasmic domain mediated cell adhesion. Furthermore, we demonstrate that the
      cytoplasmic domain of the beta 2 subunit, and within it the TTT region, are
      required for these postreceptor events. Additionally, we present a new approach,
      using deletion variants to lock integrins in a high affinity state without
      interfering with the investigated integrin/cytoskeleton interaction. This
      approach may be generally useful to investigate the role of postreceptor events
      in integrin-mediated cell adhesion and migration.

PMID- 7807012
TI  - Species-specific differences in chaperone interaction of human and mouse major
      histocompatibility complex class I molecules.
AB  - Previous studies have shown that immature mouse class I molecules transiently
      associate with a resident endoplasmic reticulum protein of 88 kD that has been
      proposed to act as a chaperone for class I assembly. Subsequently, this protein
      was demonstrated to be identical to calnexin and to associate with immature forms
      of the T cell receptor complex, immunoglobulin, and human class I HLA heavy
      chains. In this paper we define further the interaction of human class I HLA
      heavy chains with chaperone proteins and find key differences with the complexes
      observed in the mouse system. First, calnexin and immunoglobulin binding protein
      (BiP) both associate with immature HLA class I heavy chains. The two chaperones
      are not found within the same molecular complex, suggesting that calnexin and BiP
      do not interact simultaneously with the same HLA class I heavy chain. Second,
      only free HLA class I heavy chains, and not beta 2-microglobulin (beta 2m)
      associated heavy chains are found associated with the chaperones. Indeed,
      addition of free beta 2m in vitro induces dissociation of chaperone-class I HLA
      heavy chain complexes. The kinetics for dissociation of the class I HLA heavy
      chain-chaperone complexes and for formation of the class I HLA heavy chain-beta
      2m complex display a reciprocity that suggests the interactions with chaperone
      and beta 2m are mutually exclusive. Mouse class I heavy chains expressed in human
      cells exhibit the mouse pattern of interaction with human chaperones and human
      beta 2m and not the human pattern, showing the difference in behavior is purely a
      function of the class I heavy chain sequence.

PMID- 7807013
TI  - Dysregulation of interleukin 4, interleukin 5, and interferon gamma gene
      expression in steroid-resistant asthma.
AB  - In steroid-resistant (SR) asthma, there is a lack of clinical responsiveness to
      oral prednisone. Previous studies indicate that this may be explained by the
      effect of the combination of interleukin 2 (IL-2) and IL-4 on glucocorticoid
      receptor binding affinity. By contrast, steroid-sensitive (SS) asthmatics respond
      well to glucocorticoids, and this is accompanied by a decrease in the numbers of
      bronchoalveolar lavage (BAL) messenger RNA+ (mRNA+) cells expressing IL-4 and IL
      5, and an increase in interferon gamma (IFN-gamma) transcripts. In the present
      study, we hypothesized that SR asthma is associated with alterations in T helper
      types 1/2 (Th2/Th1)-type cytokine gene expression. BAL was performed in six SR
      asthmatics and six SS asthmatics, before and after a 1-wk course of 40 mg daily
      prednisone. mRNA+ cells for IL-2, IL-4, IL-5, and IFN-gamma was measured by in
      situ hybridization using 35S-labeled RNA probes. Before prednisone therapy, there
      were significantly greater numbers of BAL cells (per 1,000) expressing IL-2 mRNA
      (p < 0.01) and IL-4 mRNA (p < 0.05) in SR asthmatics as compared with SS
      asthmatics, but no differences between the two groups in the numbers of BAL cells
      expressing IFN-gamma or IL-5 mRNA expression were observed. After a 1-wk course
      of prednisone, IL-2 expression was not altered in either group. However, SS
      asthmatics had a significant decrease in the numbers of BAL cells expressing mRNA
      for IL-4 (p < 0.01) and IL-5 (p < 0.001), and a rise in the numbers of IFN-gamma
      mRNA+ cells (p < 0.01). In contrast, after prednisone treatment, SR asthmatics
      had no significant change in either the number of BAL cells expressing mRNA for
      IL-4 or IL-5. Of note, there was an unexpected decrease in the numbers of IFN
      gamma mRNA+ cells (p = 0.05). Our current findings indicate that SR asthma is
      associated with a dysregulation of the expression of the genes encoding for
      Th2/Th1 cytokines in airway cells and is compatible with the concept that a
      combination of IL-2 and IL-4 induce glucocorticoid (GR) binding affinity and T
      cell responsiveness to glucocorticoids.

PMID- 7807014
TI  - Impaired development of V gamma 3 dendritic epidermal T cells in p56lck protein
      tyrosine kinase-deficient and CD45 protein tyrosine phosphatase-deficient mice.
AB  - To determine whether p56lck protein tyrosine kinase and CD45 protein tyrosine
      phosphatase are involved in the signal transduction during intrathymic
      differentiation of gamma/delta T cells, we have examined the development of T
      cells expressing V gamma 3 T cell receptor (TCR) in mice deficient for either
      protein. The skin from both mice contained significantly reduced numbers of
      dendritic epidermal T cells expressing decreased levels of V gamma 3 TCR at the
      cell surface. Analysis of the fetal thymus from these mice suggested that
      maturation of V gamma 3 thymocytes was blocked at the immature stage that was
      characterized by the low level of V gamma 3 TCR and the high level of heat stable
      antigen. These results imply that both p56lck and CD45 are involved in the signal
      transduction during maturation of V gamma 3 T cells in the fetal thymus.

PMID- 7807015
TI  - CTLA-4 binding to the lipid kinase phosphatidylinositol 3-kinase in T cells.
AB  - CTLA-4 is a T cell antigen that is structurally related to CD28 and serves as a
      high affinity ligand for the B cell antigen B7-1/2. Unlike CD28, the function of
      CTLA-4 is unclear, although reports have implicated the antigen in the
      costimulation of T cells. Recently, phosphatidylinositol 3-kinase (PI 3-kinase)
      has been implicated in the costimulatory function of CD28 by virtue of its
      ability to bind to a pYMNM motif within the cytoplasmic tail of the antigen. In
      this study, we show that CTLA-4 can also associate with PI 3-kinase as detected
      by lipid kinase analysis and immunoblotting with anti-p85 antiserum. High
      pressure liquid chromatographic separation of deacylated lipids showed the
      presence of a peak corresponding to PI-3-P. Anti-CTLA-4 ligation of the receptor
      induced a significant increase in the levels of precipitable PI 3-kinase
      activity. Peptide binding studies revealed that the NH2- and COOH-terminal SH2
      domains of p85 bind the CTLA-4 cytoplasmic pYVKM motif with an affinity (ID50:
      0.6 and 0.04 microM), that is similar to CD28. CTLA-4 binding to PI 3-kinase
      provides further evidence that CTLA-4 is not an inert counterreceptor, but rather
      is coupled to an intracellular signaling molecule with the capacity to regulate
      cell growth.

PMID- 7807016
TI  - Transmission blocking immunity in Plasmodium vivax malaria: antibodies raised
      against a peptide block parasite development in the mosquito vector.
AB  - One approach towards the development of a vaccine against malaria is to immunize
      against the parasite sexual stages that mediate transmission of the parasite from
      man to mosquito. Antibodies against these stages, ingested with the blood meal,
      inhibit the parasite development in the mosquito vector, constituting
      "transmission blocking immunity." Most epitopes involved in transmission-blocking
      immunity depend on the tertiary conformational structure of surface antigens.
      However, one of the transmission-blocking monoclonal antibodies we have raised
      against Plasmodium vivax reacts with a linear epitope on both asexual stages and
      gametes. This monoclonal antibody (A12) is capable of totally blocking
      development of the parasite in the mosquito host when tested in membrane feeding
      assays with gametocytes from P. vivax-infected patients. Immune screening of a P.
      vivax lambda gt11 genomic expression library with A12 led to the isolation of a
      clone to which was mapped the six-amino acid epitope recognized by A12. Antisera
      raised in mice against a 12-mer synthetic peptide containing this epitope coupled
      to bovine serum albumin not only had high titers of antipeptide antibodies as
      measured by enzyme-linked immunosorbent assay, but in addition recognized the
      same 24- and 57-kD parasite components as A12 on Western blots and reacted with
      the parasite by immunofluorescence. When tested in membrane feeding assays, these
      antibodies have significant suppressive effects on parasite development in the
      mosquito.

PMID- 7807017
TI  - Mass spectrometric identification of a naturally processed melanoma peptide
      recognized by CD8+ cytotoxic T lymphocytes.
AB  - We and others have previously reported that melanoma-specific, cytotoxic T
      lymphocytes (CTL) define a minimum of six class I-presented peptide epitopes
      common to most HLA-A2+ melanomas. Here we show that three of these peptide
      epitopes are coordinately recognized by a CTL clone obtained by limiting dilution
      from the peripheral blood of an HLA-A2+ melanoma patient. Tandem mass
      spectrometry was used to characterize and sequence one of these three naturally
      processed melanoma peptides. One of the potential forms of the deduced peptide
      sequence (XXTVXXGVX, X = I or L) matches positions 32-40 of the recently
      identified melanoma gene MART-1/Melan-A. This peptide (p939; ILTVILGVL) binds to
      HLA-A2 with an intermediate-to-low affinity and is capable of sensitizing the HLA
      A2+ T2 cell line to lysis by CTL lines and clones derived from five different
      melanoma patients. A relative high frequency of anti-p939-specific effector cells
      appear to be present in situ in HLA-A2+ melanoma patients, since p939 is also
      recognized by freshly isolated tumor infiltrating lymphocytes. p939 represents a
      good candidate for the development of peptide-based immunotherapies for the
      treatment of patients with melanoma.

PMID- 7807018
TI  - Mobilization of long-term reconstituting hematopoietic stem cells in mice by
      recombinant human interleukin 7.
AB  - Administration of recombinant human interleukin 7 (rh)IL-7 to mice has been
      reported by our group to increase the exportation of myeloid progenitors (colony
      forming unit [CFU]-c and CFU-granulocyte erythroid megakarocyte macrophage) from
      the bone marrow to peripheral organs (blood, spleen[s], and liver). We now report
      that IL-7 also stimulates a sixfold increase in the number of more primitive CFU
      S day 8 (CFU-S8) and day 12 (CFU-S12) in the peripheral blood leukocytes (PBL) of
      mice treated with rhIL-7 for 7 d. Moreover, > 90% of lethally irradiated
      recipient mice that received PBL from rhIL-7-treated donor mice have survived for
      > 6 mo whereas none of the recipient mice that received an equal number of PBL
      from diluent-treated donors survived. Flow cytometry analysis at 3 and 6 mo after
      transplantation revealed complete trilineage (T, B, and myelomonocytic cell)
      repopulation of bone marrow, thymus, and spleen by blood-borne stem/progenitor
      cells obtained from rhIL-7-treated donor mice. Thus, IL-7 may prove valuable for
      mobilizing pluripotent stem cells with long-term repopulating activity from the
      bone marrow to the peripheral blood for the purpose of gene modification and/or
      autologous or allogeneic stem cell transplantation.

PMID- 7807019
TI  - Interleukin 12 is effective treatment for an established systemic intracellular
      infection: experimental visceral leishmaniasis.
AB  - When administered at or near the initiation of experimental intracellular
      infection caused by Leishmania major, Toxoplasma gondii, or Cryptococcus
      neoformans, treatment with the immuno-regulatory cytokine interleukin 12 (IL-12),
      induces protective antimicrobial activity. In contrast, once infections are
      established, IL-12 exerts considerably less or no effect in the face of a
      suppressive Th2 cell-associated response (L. major) or rapidly progressive fatal
      infection (T. gondii). To test the efficacy of IL-12 in an established
      intracellular protozoal infection but under quite different immunologic
      conditions (Th1 cell response, acquired resistance), L. donovani-infected BALB/c
      mice were treated starting 2 wk after challenge coincident with the onset of the
      Th1 cell response. In this environment, 7 d of IL-12 treatment reduced liver
      parasite burdens by 47%, an effect comparable to that induced by exogenous
      interferon (IFN) gamma. The in vivo mechanism responsive to IL-12 was complex,
      and required both CD4+ and CD8+ T cells as well as natural killer cells and the
      action of multiple endogenous antileishmanial cytokines (IFN-gamma, IL-2, tumor
      necrosis factor alpha). Early treatment with IL-12 before the expression of the
      Th1 cell response was also effective and induced an accelerated, near-cure
      response via an IFN-gamma-dependent mechanism. These results extend the
      antimicrobial-inducing capacity of IL-12 beyond prophylaxis by indicating that IL
      12 can exert clear-cut therapeutic activity in an established intracellular
      infection.

PMID- 7807020
TI  - Protective and nonprotective monoclonal antibodies to Cryptococcus neoformans
      originating from one B cell.
AB  - Two immunoglobulin M monoclonal antibodies (mAbs) derived from the same B cell
      recognize different epitopes on the capsular polysaccharide of the pathogenic
      yeast, Cryptococcus neoformans. Their respective epitopes are located in
      spatially distinct regions of the capsule. Passive administration of one mAb
      prolonged survival whereas the other mAb did not. The results indicate that
      specificity is an important determinant of antibody efficacy against C.
      neoformans and that somatic mutations occurring during the antibody response can
      affect the protective efficacy of antibodies to C. neoformans.

PMID- 7807021
TI  - Impaired mucosal immune responses in interleukin 4-targeted mice.
AB  - Interleukin 4-targeted (IL-4-/-) mice are defective in T helper (Th)2 cytokine
      production as determined after nematode infection. As Th2 cells appear to be
      selectively induced by oral immunization we investigated the ability of IL-4-/-
      mice to respond to perorally administered antigen. We found that IL-4-/- mice
      failed to respond to soluble protein antigens given perorally together with
      cholera toxin (CT) as a mucosal adjuvant. In contrast to wild-type mice no or
      poor anti-keyhole limpet hemocyanin (KLH) or anti-ovalbumin (OVA) B cell
      responses were observed in gut lamina propria, spleen, or serum of IL-4-/- mice
      after oral immunization. In addition, mucosal immunization failed to stimulate
      antigen-specific T cell responses in these mice. The lack of responsiveness was
      specific for mucosal administration of antigen and was not seen after intravenous
      injections with antigen and CT-adjuvant. The systemic adjuvant effect of CT was
      not impaired in IL-4-/- mice as evidenced by the strong enhancement of anti-KLH
      responses after intravenous immunization with KLH plus CT as opposed to KLH
      alone. However, CT as an immunogen, in contrast to KLH or OVA, stimulated
      significant mucosal and systemic immune responses in IL-4-/- mice after oral
      immunization. Both serum and intestinal IgA anti-CT antibodies were demonstrable
      in IL-4-/- mice as well as in wild-type mice. Total IgA levels in gut lavage and
      in serum of immunized IL-4-/- mice were of similar magnitude as in wild-type
      mice, suggesting that the ability of naive B cells to undergo isotype switch
      differentiation from IgM to IgA in IL-4-/- mice did not appear to be impaired.
      Immunohistochemical analysis of Peyer's patches demonstrated a complete inability
      to form germinal centers in IL-4-/- mice in contrast to wild-type mice. Our data
      suggest that IL-4-/- mice are unable to respond to oral/mucosal immunization due
      to a failure to stimulate antigen-specific cells required to induce germinal
      center reactions in the Peyer's patches. Our findings demonstrate that IL-4 and
      probably functional Th2 cells are required for induction of gut mucosal antibody
      responses.

PMID- 7807022
TI  - Activation of the p21ras pathway couples antigen receptor stimulation to
      induction of the primary response gene egr-1 in B lymphocytes.
AB  - The primary response gene egr-1 encodes a sequence-specific transcription factor
      whose expression is necessary for antigen receptor-stimulated activation of B
      lymphocytes. The molecular processes involved in linking egr-1 induction to
      antigen receptor signaling have not been defined. The present study demonstrates
      that expression of an activated form of p21ras results in egr-1 induction similar
      to that previously shown after antigen receptor cross-linking. In addition, both
      antigen receptor cross-linking and p21ras use the same element in the egr-1
      promoter to exert their effects. Using dominant-negative mutants of p21ras and
      raf-1, we demonstrate that induction of egr-1 after antigen receptor cross
      linking is mediated by activation of the p21ras/mitogen-activated protein kinase
      signaling pathway. While regulation of the p21ras pathway during B cell
      activation has been intensively studied, this report represents the first
      description of a biologically relevant event associated with its activation.

PMID- 7807023
TI  - CD8+ T lymphocytes provide helper activity for IgE synthesis in human
      immunodeficiency virus-infected patients with hyper-IgE.
AB  - Increased levels of serum IgE and eosinophilia have been described in human
      immunodeficiency virus (HIV) infection, almost exclusively in patients with CD4+
      cell count < 200 cells/microliters. IgE production is regulated by CD4+ T helper
      type 2 (Th-2) lymphocytes, producing interleukin 4 (IL-4) and expressing a ligand
      for the B cell-specific CD40 molecule (CD40 ligand [L]). A shift to a Th-2-like
      pattern of cytokine secretion has been postulated to be associated with
      progression toward acquired immunodeficiency syndrome (AIDS). We studied three
      AIDS patients with very high levels of IgE and almost complete depletion of CD4+
      lymphocytes, suggesting that IgE synthesis could not be driven by CD4+ cells. IgE
      in vitro synthesis by cells from such patients was, however, inhibited by anti-IL
      4. We show that both CD8+ T cell lines and the majority of CD8+ T cells clones
      derived from these patients produce IL-4, IL-5, and IL-6 in half of the cases
      together with interferon gamma (IFN-gamma). 44% of CD8+ T cell clones expressed a
      CD40L, and the supernatants of the clones were capable of inducing IgE synthesis
      by normal B cells costimulated with anti-CD40. CD8+ T cells in these patients
      therefore functionally mimic Th-2 type cells and may account for hyper-IgE and
      eosinophilia in the absence of CD4+ cells. The presence of such CD8+ cells may
      also provide a source of IL-4 directing the development of predominant Th-2
      responses in HIV infection.

PMID- 7807024
TI  - Inhibition of tumor growth by elimination of granulocytes.
AB  - As observed for many types of cancers, heritable variants of ultraviolet light
      induced tumors often grow more aggressively than the parental tumors. The
      aggressive growth of some variants is due to the loss of a T cell-recognized
      tumor-specific antigen; however, other variants retain such antigens. We have
      analyzed an antigen retention variant and found that the variant tumor cells grow
      at the same rate as the parental tumor cells in vitro, but grew more rapidly than
      the parental cells in the T cell-deficient host. The growth of the variant cells
      was stimulated in vitro by factors released from tumor-induced leukocytes and by
      several defined growth factors. In addition, the variant cancer cells actually
      attracted more leukocytes in vitro than the parental cells. Furthermore,
      elimination of granulocytes in vivo in nude mice by a specific antigranulocyte
      antibody inhibited the growth of the variant cancer, indicating that this tumor
      requires granulocytes for rapid growth.

PMID- 7807025
TI  - The functional role of CD8+ T helper type 2 cells.

PMID- 7807026
TI  - Human HLA-A0201-restricted cytotoxic T lymphocyte recognition of influenza A is
      dominated by T cells bearing the V beta 17 gene segment.
AB  - The major histocompatibility complex class I-restricted cytotoxic T lymphocyte
      (CTL) response is important in the clearance of viral infections in humans. After
      influenza A infection, a peptide from the matrix protein, M58-66, is presented in
      the context of the MHC allele HLA-A0201 and the resulting CTL response is
      detectable in most HLA-A0201 subjects. An initial study suggested that M58-66
      specific CTL clones show conserved T cell receptor (TCR) alpha and beta gene
      segments. We have addressed the significance of this observation by determining
      the expression of V beta 17 during the development of M58-66-specific CTL lines
      in 21 unrelated HLA-A0201 subjects, and analyzing TCR usage by M58-66-specific
      CTL clones. TCR V beta 17 was the dominant V beta segment used and CD8 V beta 17
      expansion correlated with M58-66-specific lysis. Limiting dilution analysis from
      five subjects showed the M58-66 CTL precursor frequency to vary between 1/54,000
      and less than 1/250,000, and that up to 85% of the matrix peptide (M58-66)
      specific CTL used the V beta 17 gene segment. The M58-66 specific CTL response
      was dependent on previous viral exposure and specific V beta 17 expansion, as it
      was not found in cord blood, despite a readily expandable V beta 17+ CD8+ T cell
      subpopulation. Sequence analysis of 38 M58-66-specific V beta 17 transcripts from
      13 subjects revealed extensive conservation in the CDR3 region including
      conservation of an arginine-serine motif. To test the dependence of this CTL
      response on the V beta 17 gene segment, peripheral blood lymphocytes were
      depleted of CD8+ TCR V beta 17+ cells, before the generation of M58-66-specific
      CTL. In most cases such depletion blocked or severely reduced the generation of
      the M58-66-specific response, and under limiting dilution conditions could
      abolish M58-66-specific CTL precursors. These studies reveal the dependence of
      this natural human immune response on a particular TCR gene segment.

PMID- 7807028
TI  - OTC nicotine gum.

PMID- 7807027
TI  - Phenotypic analysis of murine long-term hemopoietic reconstituting cells
      quantitated competitively in vivo and comparison with more advanced colony
      forming progeny.
AB  - Early hemopoietic precursors have been extensively studied using short-term
      assays based on colony formation or in vivo reconstitution that do not run beyond
      a few weeks. However, little information is available on the phenotype of the
      stem cells that are detectable in 6-12-mo transplantation assays, and their
      relationship to cells detected in short-term assays is not known. In this study,
      we investigated the phenotype and separability by cell sorting of a spectrum of
      hemopoietic precursor cells in normal adult mouse marrow, including cells
      quantitated in a 1 yr competitive transplantation assay in vivo as well as in
      short-term colony assays in vitro and in vivo. Two principal findings emerged.
      The first was that cells detected in a variety of short-term assays--CFU-S12
      (spleen colony-forming cells), CFCmulti (multilineage colony-forming cells), pre
      CFCmulti (precursors of CFCmulti), CFC-E/Mg (erythroid/megakaryocyte CFC) and CFC
      G/M (granulocyte/macrophage CFC)--were phenotypically similar and could not be
      separated from one another using a panel of markers useful in segregating them
      from more differentiated cells, including buoyant density, sedimentation
      velocity, adhesiveness to plastic, light scatter, high rhodamine-123 retention,
      and expression of surface wheat-germ agglutinin (WGA)-binding carbohydrate, H-2K,
      CD45, AA4.1, heat stable antigen (HSA), CD71, and Ly6A/Sca-1 antigens. Long-term
      reconstituting (LTR) cells quantitated in vivo differed little from the other
      precursors in expression of many of the above markers. However, they differed
      somewhat in lower sedimentation velocity and lower expression of WGA-binding
      surface carbohydrate, and most strikingly in their conditional adhesiveness to
      plastic, very low retention of Rh123 and high level expression of Ly6A/Sca-1, to
      a degree that would permit the quantitative separation of the two precursor
      classes from each other. The results provide a comprehensive characterization of
      LTR cells measured to 12 mo in vivo and a direct and quantitative analysis of
      their separation from cells detected in colony assays.

PMID- 7807029
TI  - OTC nicotine gum.

PMID- 7807030
TI  - Occupational dermatitis.

PMID- 7807031
TI  - Ensuring patient confidentiality.

PMID- 7807032
TI  - Pearls.

PMID- 7807033
TI  - Does pseudoephedrine increase blood pressure in patients with controlled
      hypertension?
AB  - BACKGROUND: The use of the decongestant pseudoephedrine has been avoided in
      hypertensive patients with little evidence to support this caution. The purpose
      of this study was to determine the effects of therapeutic doses of
      pseudoephedrine on blood pressure in patients with controlled hypertension.
      METHODS: Twenty-five patients with controlled hypertension were enrolled in a
      randomized, placebo-controlled, double-blind crossover trial. This was a 4-week
      study in which all participants received placebo during the 1st and 3rd weeks.
      Subjects were randomly assigned to receive pseudoephedrine or placebo during the
      2nd week of the study, and to receive the opposite during the 4th week of the
      study. Blood pressure readings were taken at the beginning and end of each week
      of the trial, and at a 1-week poststudy follow-up visit. RESULTS: The mean
      systolic pressure was 133 mm Hg in patients receiving both pseudoephedrine and
      placebo (P = NS). The mean diastolic pressure was 82 mm Hg in patients receiving
      pseudoephedrine and 82.5 mm Hg in patients receiving placebo. Mean pulse rates
      were 76.8 and 75.2 beats per minute in patients given pseudoephedrine and those
      given placebo, respectively (P = NS). There were no statistically significant or
      clinically important differences in the mean systolic or mean diastolic blood
      pressures among the groups during the entire 4-week course of the study.
      CONCLUSIONS: At standard doses, pseudoephedrine has no significant effect on
      systolic or diastolic blood pressure in patients with controlled hypertension.

PMID- 7807034
TI  - Cancer screening and detection in family practice: a MIRNET study.
AB  - BACKGROUND: The identification of effective strategies for the prevention,
      diagnosis, and treatment of cancer is a high priority for the nation, yet
      relatively little is known about how cancer is diagnosed in primary care. This
      study was undertaken to describe practitioner beliefs about cancer screening and
      to determine whether beliefs and intentions about cancer screening are associated
      with actual cancer detection rates among asymptomatic patients cared for by
      family physicians. METHODS: A self-administered questionnaire on cancer screening
      beliefs and practices was completed by members of the Michigan Research Network
      (MIRNET) in January 1990 and again in December of 1990. Thirty-one practitioners
      prospectively identified all patients with a new diagnosis of cancer during 1990.
      RESULTS: One hundred sixteen cancer cases were identified. Only 31% of the 77
      cancers considered to be potentially detectable by routine screening were
      actually identified by screening. Physicians reporting more aggressive screening
      practices identified greater percentages of asymptomatic cancers and a greater
      number of breast and colon cancers. CONCLUSIONS: Low percentages of cancers were
      detected in asymptomatic patients in this population. Practitioner attitudes
      about the need for cancer screening appear to be an important component of cancer
      detection.

PMID- 7807035
TI  - Nebulized bacteriostatic saline as a cause of bronchitis.
AB  - BACKGROUND: The purpose of this study was to determine whether nebulized
      bacteriostatic saline, which contains the preservative benzyl alcohol, is an
      irritant to the tracheobronchial mucosa in healthy adults. METHODS: A randomized,
      double-blind, placebo-controlled study was conducted with 10 healthy adults who
      inhaled 3 mL of either bacteriostatic saline or saline placebo by nebulizer four
      times a day for 2 weeks. Pulmonary function tests and bronchoscopy with biopsy
      were performed immediately before and after the 2-week nebulization period.
      RESULTS: Nine of 10 volunteers were compliant with the study protocol. Four of
      five volunteers who used nebulized bacteriostatic saline developed bronchitic
      symptoms and had bronchoscopic evidence of bronchitis. The fifth remained
      healthy. Four volunteers used nebulized saline (placebo). Two of these four
      became ill, one with a much more severe bronchitis than any of the bacteriostatic
      saline volunteers, and one with pharyngitis. Bronchoscopic biopsies showed a
      lymphocytic mucosal infiltrate in those who became ill while using nebulized
      bacteriostatic saline and a polymorphonuclear mucosal infiltrate in those who
      became ill while using nebulized saline placebo. CONCLUSIONS: Nebulization of
      bacteriostatic saline, containing benzyl alcohol as its preservative, causes
      bronchitis in healthy adults. Even nebulization of sterile saline may be
      associated with bronchitis and pharyngitis. Physicians who prescribe nebulized
      medications must pay close attention to the bronchodilator diluent.

PMID- 7807036
TI  - Health care professionals' accuracy in predicting patients' preferred code
      status.
AB  - BACKGROUND: In spite of the emphasis on physician and patient communication in
      the new guidelines for the use of do-not-resuscitate orders published by the
      American Medical Association, informal information indicates that physicians and
      other health care professionals often formulate code status decisions without
      formal knowledge of the patient's wishes. The purpose of this study was to
      determine how accurately health care professionals are able to predict a
      patient's desired code status given a profile of the patient's medical history.
      METHODS: A consecutive sample of physicians and other health care professionals
      attending on-site primary care and long-term rehabilitation staff meetings were
      asked to participate in the study. Subjects read profiles of actual patients and
      attempted to predict the patients' desired code status. Subjects also highlighted
      factors of the patient profile that they deemed important in predicting each
      patient's desired code status. RESULTS: For the 12 patient profiles examined, the
      respondents accurately estimated patients' desired code status an average of only
      6.5 times. Patient ability to perform the basic activities of daily living was
      the patient profile factor cited most frequently as influential in determining
      code status. CONCLUSIONS: Given only clinical and demographic data, health care
      professionals are only slightly better than chance in determining patients'
      desired code status. Health care professionals working with long-term care
      patients should become familiar with individual patient's values and desires for
      code status decisions.

PMID- 7807037
TI  - Urinalysis predictive of urine culture results.
AB  - BACKGROUND: Most clinicians treat patients for presumptive urinary tract
      infections based on urinalysis findings. Which of these findings is the best
      predictor of infection? METHODS: A retrospective cross-sectional study of 202
      serial subjects of all ages was conducted over 8 months in a typical family
      medicine setting. Urinalysis and culture were performed concurrently. RESULTS:
      The best predictors for significant bacteriuria (defined as a culture with more
      than 50,000 colony-forming units) were > or = 2+ bacteriuria (sensitivity, 0.74;
      specificity, 0.80), or > or = 10 white blood cells per high-power field
      (sensitivity, 0.816; specificity, 0.651), or a positive nitrite test
      (sensitivity, 0.395; specificity, 0.929). The optimal combination of any two of
      the three predictor variables also was determined. CONCLUSIONS: Standard
      urinalysis results can be highly predictive of infection in typical family
      practice patients.

PMID- 7807038
TI  - Characteristics of community-based primary care physicians participating in
      research.
AB  - BACKGROUND: Participation of community-based primary care practitioners in
      practice-based research has been encouraged for several years. The purpose of
      this study was to examine characteristics related to community-based primary care
      physician participation in research activities. METHODS: This study is a
      secondary analysis of the survey "Practice Patterns of Young Physicians, 1987:
      United States," which was originally conducted by the American Medical
      Association. The respondents were full-time primary care physicians (family or
      general practice, pediatrics, general internal medicine) who were not employed by
      a medical school or a university (N = 1713). RESULTS: Seven percent of
      practitioners not affiliated with a medical school reported spending at least
      some time during the previous week conducting medical research. Among community
      based physicians with faculty appointments, only 20% spend any time engaged in
      research activities during the same time frame. Among community-based
      practitioners affiliated with a medical school, researchers saw significantly
      fewer patients per week than did nonresearchers. However, there was no difference
      between researchers and nonresearchers in terms of specialty, total weekly work
      hours, or annual income. CONCLUSIONS: Based on the data used in this analysis,
      only a small proportion of community-based primary care physicians participate in
      research. Physicians affiliated with medical schools conducted research at nearly
      three times the rate of unaffiliated physicians. However, participation in
      research activities had little impact on community physicians' workload or
      income.

PMID- 7807039
TI  - A comparison of the reliability of repeat cervical smears and colposcopy in
      patients with abnormal cervical cytology.
AB  - BACKGROUND: To determine the reliability of repeat cervical smears (Papanicolaou
      smears) in patients who have had an abnormal initial smear, prospective data were
      collected on patients being followed up for a previously abnormal cervical smear.
      METHODS: All 428 patients who were referred for colposcopy because of abnormal
      cervical smears underwent simultaneous cervical smears and coloposcopy with
      directed biopsy. Patients with colposcopic evidence of invasive carcinoma or a
      history of prior colposcopy were excluded. Cervical smear results were compared
      with the histologic findings on colposcopically directed biopsy. The ability of
      cervical smears to identify cervical intraepithelial neoplasia (CIN) and high
      grade lesions (CIN 2 and 3) were also calculated for the repeat cervical smear.
      RESULTS: The sensitivity of repeat Papanicolau screening for CIN was 48%. When
      differentiating high-grade lesions from low-grade and benign biopsies, the
      sensitivity of the repeat cervical smear was only 25%. Of 110 patients with
      biopsy-proven high-grade lesions, 68% had low-grade initial cervical smears and
      73% had low-grade or benign repeat cervical smear cytology. CONCLUSIONS: This
      study demonstrates that repeated Pap smears often fail to identify high-grade
      lesions and that the sensitivity of a repeat cervical smear is very low in
      patients with low-grade abnormalities found on routine screening examinations.
      Using follow-up cervical smears to monitor patients who have low-grade squamous
      intraepithelial lesions (LGSIL) carries unacceptable risks. A more reliable
      diagnostic test such as colposcopy is indicated.

PMID- 7807040
TI  - Improving outcomes in diabetes: a review of the outpatient care of NIDDM
      patients.
AB  - This article is a critical review of the recent medical literature on the
      outpatient care of patients with non-insulin-dependent diabetes mellitus (type
      II). The 1989 consensus statement of the American Diabetes Association,
      "Standards of Medical Care for Patients with Diabetes Mellitus," has been
      selected as an initial point of departure. The author's goal is to present an
      evidence-based approach to the outpatient care of patients with type II diabetes
      in a way that is practical, strategically focused, and consistent with the basic
      philosophy of family practice. This article sets forth a detailed flow sheet for
      the implementation of this approach by the nurse and physician working as a team.

PMID- 7807041
TI  - BCG vaccination and the PPD test: what the clinician needs to know.
AB  - The resurgence in tuberculosis necessitates careful surveillance and sensitive
      detection of cases. The purified protein derivative (PPD) test is the foundation
      of tuberculosis control. Primary care clinicans are encountering increasing
      numbers of persons immigrating from countries in which BCG (bacille Calmette
      Guerin) vaccination is common. Many health care providers believe that previous
      BCG vaccination usually results in a positive PPD test, and therefore consider
      BCG vaccination status when interpreting a positive result on the PPD test. All
      articles listed in MEDLINE that included BCG and PPD as key words, a total of 62,
      were reviewed. Articles published before computerization of the medical
      literature, a total of 35, were reviewed in Index Medicus. This literature review
      indicates that there is little relationship between BCG vaccination and PPD
      positivity, and that BCG vaccination status should not be considered in the
      interpretation of a positive PPD test.

PMID- 7807042
TI  - Vaginal intraepithelial neoplasia III detected after hysterectomy for benign
      conditions.
AB  - Because primary vaginal cancer is rare, many experts discourage routine cytologic
      sampling of the vaginal vault following hysterectomy for benign circumstances.
      The following report describes a case of vaginal intraepithelial neoplasia III
      (VAIN III) detected by a vaginal vault Papanicolaou smear obtained from an
      asymptomatic 57-year-old woman 23 years after she had a total abdominal
      hysterectomy for a benign condition. As VAIN III is a true vaginal cancer
      precursor, the innocent disregard of recommended screening practices averted
      significant morbidity and possibility mortality for this otherwise healthy woman.

PMID- 7807043
TI  - Dystonic-like reaction following cisapride therapy.
AB  - A 43-year-old woman with gastroesophageal reflux disease developed a dystonic
      like reaction approximately 3 days after starting oral cisapride therapy. Office
      evaluation revealed a patient who moved her head rhythmically from side to side
      as she stared into space, generally unresponsive to external stimuli. She had
      increased tone of the sternocleidomastoid muscles bilaterally, with occasional
      tongue protrusion, and a slow shuffling gait. Following discontinuation of
      cisapride, the patient recovered completely.

PMID- 7807044
TI  - Isolated iron deficiency: an atypical manifestation of celiac disease.
AB  - A 38-year-old woman presented with iron-deficiency anemia in 1983. Eight years
      later, she developed classic symptoms of celiac disease, ie, diarrhea, weight
      loss, and diminished appetite. New noninvasive blood tests and the ease with
      which small bowel biopsies can be achieved are having an impact on the clinical
      pattern of the disease. This report includes a discussion of anemia as the
      presenting sign of celiac disease and a review of the literature.

PMID- 7807045
TI  - Inhaled albuterol to treat bronchitis.

PMID- 7807046
TI  - Does aspirin heal leg ulcers?

PMID- 7807047
TI  - Partial reactions of the Na,K-ATPase: determination of rate constants.
AB  - Experiments were designed to characterize several partial reactions of the Na,K
      ATPase and to demonstrate that a model can be defined that reproduces most of the
      transport features of the pump with a single set of kientic parameters. We used
      the fluorescence label 5-iodoacetamidofluorescein, which is thought to be
      sensitive to conformational changes, and the styryl dye RH 421, which can be
      applied to detect ion-binding and -release reactions. In addition transient
      electric currents were measured, which are associated mainly with the E1-->E2
      conformational transition. Numerical simulations were performed on the basis of a
      reaction model, that has been developed from the Post-Albers cycle. Analysis of
      the experimental data allows the determination of several rate constants of the
      pump cycle. Our conclusions may be summarized as follows: (a) binding of one Na+
      ion at the cytoplasmic face is electrogenic. This Na+ ion is specifically bound
      to a neutral binding site with an affinity of 8 mM in the presence of 10 mM Mg2+.
      In the absence of divalent cations, the intrinsic binding affinity was found to
      be 0.7 mM. (b) The analysis of fluorescence experiments with the cardiotonic
      steroid strophanthidin indicates that the 5-iodoacetamidofluorescein label
      monitors the conformational transition (Na3)E1-P-->P-E2(Na2), which is
      accompanied by the release of one Na+ ion. 5-IAF does not respond to the release
      of the subsequent two Na+ ions, which can be monitored by the RH 421 dye. These
      experiments indicate further that the conformational transition E1P-->P-E2 is the
      rate limiting process of the Na+ translocation. The corresponding rate constant
      was determined to be 22 s-1 at 20 degrees C. From competition experiments with
      cardiotonic steroids, we estimated that the remaining 2 Na+ ions are released
      subsequently with a rate constant of at least 5,000 s-1 from their negatively
      charged binding sites. (c) Comparing the fluorescence experiments with electric
      current transients, which were performed at various Na concentrations in the
      absence and presence of strophanthidin, we found that the transition (Na3).E1-P-
      >P-E2.(Na2) is the major charge translocating step in the reaction sequence
      Na3.E1-->(Na3).E1-P-->P-E2.(Na2)-->P-E2. The subsequent release of 2 Na+ ions
      contributed less than 25% to the total electric current transient. (d) The well
      known antagonism between cardiotonic steroids and K+ binding can be explained by
      a kinetic model. A quantitative description has been obtained under the
      assumption that these inhibitors bind only to the states P-E2(Na2) and P
      E2(K2).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7807048
TI  - Alteration of the transmembrane K+ gradient during development of delayed
      rectifier in isolated rat pulmonary arterial cells.
AB  - The properties of the tail current associated with the delayed rectifier K+
      current (IK) in isolated rat pulmonary artery smooth muscle cells were examined
      using the whole cell patch clamp technique. The tail currents observed upon
      repolarization to -60 mV after brief (e.g., 20 ms) or small (i.e. to potentials
      negative of 0 mV) depolarizations were outwardly directed, as expected given the
      calculated K+ reversal potential of -83 mV. The tail currents seen upon
      repolarization after longer (e.g., 500 ms) and larger (e.g., to +60 mV)
      depolarizations tended to be inwardly directed. Depolarizations of intermediate
      strength and/or duration were followed by biphasic tail currents, which were
      inwardly directed immediately upon repolarization, but changed direction and
      became outwardly directed before deactivation was complete. When cells were
      depolarized to +60 mV for 500 ms both IK and the subsequent inward tail current
      at -60 mV were similarly blocked by phencyclidine. Both IK and the inward tail
      current were also blocked by 4-aminopyridine. Application of progressively more
      depolarized 30 s preconditioning potentials inactivated IK, and reduced the
      inward tail current amplitude with a similar potential dependency. These results
      indicated that the inward tail current was mediated by IK. The reversal potential
      of the tail current became progressively more positive with longer
      depolarizations to +60 mV, shifting from -76.1 +/- 2.2 mV (n = 10) after a 20-ms
      step to -57.7 +/- 3.5 mV (n = 9) after a 500-ms step. Similar effects occurred
      when extracellular K+ and Na+ were replaced by choline. When extracellular K+ was
      raised to 50 mM, the tail current was always inwardly directed at -60 mV, but
      showed little change in amplitude as the duration of depolarization was
      increased. These observations are best explained if the dependencies of tail
      current direction and kinetics upon the duration of the preceding depolarization
      result from an accumulation of K+ at the external face of the membrane, possibly
      in membrane invaginations. A mathematical model which simulates the reversal
      potential shift and the biphasic kinetics of the tail current on this basis is
      presented.

PMID- 7807049
TI  - A novel mechanism for the Ca(2+)-sensitizing effect of protein kinase C on
      vascular smooth muscle: inhibition of myosin light chain phosphatase.
AB  - Mechanisms of Ca2+ sensitization of both myosin light chain (MLC) phosphorylation
      and force development by protein kinase C (PKC) were studied in permeabilized
      tonic smooth muscle obtained from the rabbit femoral artery. For comparison, the
      Ca2+ sensitizing effect of guanosine 5'-O-(gamma-thiotriphosphate) (GTP gamma S)
      was examined, which had been previously shown to inhibit MLC phosphatase in
      phasic vascular smooth muscle. We now report that PKC activators (phorbol esters,
      short chain synthetic diacylglycerols and a diacylglycerol kinase inhibitor) and
      GTP gamma S significantly increase both MLC phosphorylation and force development
      at constant [Ca2+]. Major phosphorylation site occurring in the presence of
      phorbol-12,13-dibutyrate (PDBu) or GTP gamma S at constant [Ca2+] is the same
      serine residue (Ser-19) as that phosphorylated by MLC kinase in response to
      increased Ca2+ concentrations. In an ATP- and Ca(2+)-free solution containing 1
      (5-chloronaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine (ML-9), to avoid the
      kinase activity, both PDBu and GTP gamma S significantly decreased the rate of
      MLC dephosphorylation to half its control value. However, PDBu inhibited the
      relaxation rate more than did GTP gamma S. In the presence of microcystin-LR to
      inhibit the phosphatase activity, neither PDBu nor GTP gamma S affected MLC
      phosphorylation and force development. These results indicate that PKC, like
      activation of GTP binding protein, increases Ca2+ sensitivity of both MLC
      phosphorylation and force production through inhibition of MLC phosphatase.

PMID- 7807050
TI  - Characterization of impulse propagation at the microscopic level across
      geometrically defined expansions of excitable tissue: multiple site optical
      recording of transmembrane voltage (MSORTV) in patterned growth heart cell
      cultures.
AB  - Impulse propagation across sudden expansions of excitable tissue has been shown
      to exhibit various forms of conduction disturbance on a macroscopic scale,
      ranging from small delays to unidirectional or complete conduction block. With
      the present study, we attempted to characterize systematically the dependence of
      impulse propagation on the geometry of the underlying excitable tissue on a
      microscopic scale by investigating the spatio-temporal pattern of transmembrane
      voltage changes associated with impulse propagation from a narrow cell strand to
      a large cell area using multiple site optical recording of transmembrane voltage
      (MSORTV) in conjunction with patterned growth of neonatal rat heart cells in
      culture. While action potential propagation was smooth in the case of funneled
      expansions, delays of variable size occurred during propagation into rectangular
      or incised expansions. Close to the abrupt expansion, which functionally
      represented an increased electrical load to the narrow cell strand, the delays
      were accompanied by marked distortions of the action potential upstroke,
      exhibiting, in extreme cases, an initial depolarization to 50% followed by a
      delayed secondary depolarization to 100% of the full-signal amplitude. These
      distortions, which were based on bidirectional electrotonic interactions across
      the transition, were maximal immediately downstream from the expansion. The
      maximal slowing of impulse conduction across abrupt expansions was, in agreement
      with recently published results obtained from two-dimensional computer
      simulations, always situated in the expanded region. At high stimulation rates,
      the delays sometimes turned into intermittent unidirectional blocks, as revealed
      by reverse stimulation. These blocks were always characterized by a marked
      abbreviation of the action potentials upstream from the region causing the block
      which might, in an appropriate network, facilitate reentry because of the
      associated shortening of the refractory period. Because the patterns were
      composed of cells having identical membrane properties, the results show that the
      local action potential shape can be modulated profoundly by the two-dimensional
      architecture of the underlying cell ensemble alone.

PMID- 7807051
TI  - Inactivation of N-type calcium current in chick sensory neurons: calcium and
      voltage dependence.
AB  - We have studied the inactivation of high-voltage-activated (HVA), omega-conotoxin
      sensitive, N-type Ca2+ current in embryonic chick dorsal root ganglion (DRG)
      neurons. Voltage steps from -80 to 0 mV produced inward Ca2+ currents that
      inactivated in a biphasic manner and were fit well with the sum of two
      exponentials (with time constants of approximately 100 ms and > 1 s). As reported
      previously, upon depolarization of the holding potential to -40 mV, N current
      amplitude was significantly reduced and the rapid phase of inactivation all but
      eliminated (Nowycky, M. C., A. P. Fox, and R. W. Tsien. 1985. Nature. 316:440
      443; Fox, A. P., M. C. Nowycky, and R. W. Tsien. 1987a. Journal of Physiology.
      394:149-172; Swandulla, D., and C. M. Armstrong. 1988. Journal of General
      Physiology. 92:197-218; Plummer, M. R., D. E. Logothetis, and P. Hess. 1989.
      Neuron. 2:1453-1463; Regan, L. J., D. W. Sah, and B. P. Bean. 1991. Neuron. 6:269
      280; Cox, D. H., and K. Dunlap. 1992. Journal of Neuroscience. 12:906-914). Such
      kinetic properties might be explained by a model in which N channels inactivate
      by both fast and slow voltage-dependent processes. Alternatively, kinetic models
      of Ca-dependent inactivation suggest that the biphasic kinetics and holding
      potential-dependence of N current inactivation could be due to a combination of
      Ca-dependent and slow voltage-dependent inactivation mechanisms. To distinguish
      between these possibilities we have performed several experiments to test for the
      presence of Ca-dependent inactivation. Three lines of evidence suggest that N
      channels inactivate in a Ca-dependent manner. (a) The total extent of
      inactivation increased 50%, and the ratio of rapid to slow inactivation increased
      approximately twofold when the concentration of the Ca2+ buffer, EGTA, in the
      patch pipette was reduced from 10 to 0.1 mM. (b) With low intracellular EGTA
      concentrations (0.1 mM), the ratio of rapid to slow inactivation was additionally
      increased when the extracellular Ca2+ concentration was raised from 0.5 to 5 mM.
      (c) Substituting Na+ for Ca2+ as the permeant ion eliminated the rapid phase of
      inactivation. Other results do not support the notion of current-dependent
      inactivation, however. Although high intracellular EGTA (10 mM) or BAPTA (5 mM)
      concentrations suppressed the rapid phase inactivation, they did not eliminate
      it. Increasing the extracellular Ca2+ from 0.5 to 5 mM had little effect on this
      residual fast inactivation, indicating that it is not appreciably sensitive to
      Ca2+ influx under these conditions.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7807053
TI  - Characterization of the calcium-activated chloride channel in isolated guinea-pig
      hepatocytes.
AB  - Macroscopic and unitary currents through Ca(2+)-activated Cl- channels were
      examined in enzymatically isolated guinea-pig hepatocytes using whole-cell,
      excised outside-out and inside-out configurations of the patch-clamp technique.
      When K+ conductances were blocked and the intracellular Ca2+ concentration
      ([Ca2+]i) was set at 1 microM (pCa = 6), membrane currents were observed under
      whole-cell voltage-clamp conditions. The reversal potential of the current
      shifted by approximately 60 mV per 10-fold change in the external Cl-
      concentration. In addition, the current did not appear when Cl- was omitted from
      the internal and external solutions, indicating that the current was Cl-
      selective. The current was activated by increasing [Ca2+]i and was inactivated in
      Ca(2+)-free, 5 mM EGTA internal solution (pCa > 9). The current was inhibited by
      bath application of 9-anthracenecarboxylic acid (9-AC) and 4,4'
      diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) in a voltage-dependent
      manner. In single channel recordings from outside-out patches, unitary current
      activity was observed, whose averaged slope conductance was 7.4 +/- 0.5 pS (n =
      18). The single channel activity responded to extracellular Cl- changes as
      expected for a Cl- channel current. The open time distribution was best described
      by a single exponential function with mean open lifetime of 97.6 +/- 10.4 ms (n =
      11), while at least two exponentials were required to fit the closed time
      distributions with a time constant for the fast component of 21.5 +/- 2.8 ms (n =
      11) and that for the slow component of 411.9 +/- 52.0 ms (n = 11). In excised
      inside-out patch recordings, channel open probability was sensitive to [Ca2+]i.
      The relationship between [Ca2+]i and channel activity was fitted by the Hill
      equation with a Hill coefficient of 3.4 and the half-maximal activation was 0.48
      microM. These results suggest that guinea-pig hepatocytes possess Ca(2+)
      activated Cl- channels.

PMID- 7807052
TI  - Role of intracellular Ca2+ in stimulation-induced increases in transmitter
      release at the frog neuromuscular junction.
AB  - Under conditions of reduced quantal content, repetitive stimulation of a
      presynaptic nerve can result in a progressive increase in the amount of
      transmitter released by that nerve in response to stimulation. At the frog
      neuromuscular junction, this increase in release has been attributed to four
      different processes: first and second components of facilitation, augmentation,
      and potentiation (e.g., Zengel, J. E., and K. L. Magleby. 1982. Journal of
      General Physiology. 80:583-611). It has been suggested that an increased entry of
      Ca2+ or an accumulation of intraterminal Ca2+ may be responsible for one or more
      of these processes. To test this hypothesis, we have examined the role of
      intracellular Ca2+ in mediating changes in end-plate potential (EPP) amplitude
      during and after repetitive stimulation at the frog neuromuscular junction. We
      found that increasing the extracellular Ca2+ concentration or exposing the
      preparation to carbonyl cyanide m-chlorophenylhydrazone, ionomycin, or
      cyclopiazonic acid all led to a greater increase in EPP amplitude during
      conditioning trains of 10-200 impulses applied at a frequency of 20 impulses/s.
      These experimental manipulations, all of which have been shown to increase
      intracellular levels of Ca2+, appeared to act by increasing primarily the
      augmentation component of increased release. The results of this study are
      consistent with previous suggestions that the different components of increased
      release represent different mechanisms, and that Ca2+ may be acting at more than
      one site in the nerve terminal.

PMID- 7807054
TI  - Caffeine activates a Ca(2+)-permeable, nonselective cation channel in smooth
      muscle cells.
AB  - The effects of caffeine on cytoplasmic [Ca2+] ([Ca2+]i) and plasma membrane
      currents were studied in single gastric smooth muscle cells dissociated from the
      toad, Bufo marinus. Experiments were carried out using Fura-2 for measuring
      [Ca2+]i and tight-seal voltage-clamp techniques for recording membrane currents.
      When the membrane potential was held at -80 mV, in 15% of the cells studied
      caffeine increased [Ca2+]i without having any effect on membrane currents. In
      these cells ryanodine completely abolished any caffeine induced increase in
      [Ca2+]i. In the other cells caffeine caused both an increase in [Ca2+]i and
      activation of an 80-pS nonselective cation channel. In this group of cells
      ryanodine only partially blocked the increase in [Ca2+]i induced by caffeine;
      moreover, the change in [Ca2+]i that did occur was tightly coupled to the time
      course and magnitude of the cation current through these channels. In the
      presence of ryanodine, blockade of the 80-pS channel by GdCl3 or decreasing the
      driving force for Ca2+ influx through the plasma membrane by holding the membrane
      potential at +60 mV almost completely blocked the increase in [Ca2+]i induced by
      caffeine. Thus, the channel activated by caffeine appears to be permeable to
      Ca2+. Caffeine activated the cation channel even when [Ca2+]i was clamped to
      below 10 nM when the patch pipette contained 10 mM BAPTA suggesting that caffeine
      directly activates the channel and that it is not being activated by the increase
      in Ca2+ that occurs when caffeine is applied to the cell. Corroborating this
      suggestion were additional results showing that when the membrane was depolarized
      to activate voltage-gated Ca2+ channels or when Ca2+ was released from carbachol
      sensitive internal Ca2+ stores, the 80-pS channel was not activated. Moreover,
      caffeine was able to activate the channel in the presence of ryanodine at both
      positive and negative potentials, both conditions preventing release of Ca2+ from
      stores and the former preventing its influx. In summary, in gastric smooth muscle
      cells caffeine transiently releases Ca2+ from a ryanodine-sensitive internal
      store and also increases Ca2+ influx through the plasma membrane by activating an
      80-pS cation channel by a mechanism which does not seem to involve an elevation
      of [Ca2+]i.

PMID- 7807055
TI  - Simultaneous measurement of Ca2+ release and influx into smooth muscle cells in
      response to caffeine. A novel approach for calculating the fraction of current
      carried by calcium.
AB  - Activation of ryanodine receptors on the sarcoplasmic reticulum of single smooth
      muscle cells from the stomach muscularis of Bufo marinus by caffeine is
      accompanied by a rise in cytoplasmic [Ca2+] ([Ca2+]i), and the opening of
      nonselective cationic plasma membrane channels. To understand how each of these
      pathways contributes to the rise in [Ca2+]i, one needs to separately monitor Ca2+
      entry through them. Such information was obtained from simultaneous measurements
      of ionic currents and [Ca2+]i by the development of a novel and general method to
      assess the fraction of current induced by an agonist that is carried by Ca2+.
      Application of this method to the currents induced in these smooth muscle cells
      by caffeine revealed that approximately 20% of the current passing through the
      membrane channels activated following caffeine application is carried by Ca2+.
      Based on this information we found that while Ca2+ entry through these channels
      rises slowly, release of Ca2+ from stores, while starting at the same time, is
      much faster and briefer. Detailed quantitative analysis of the Ca2+ release from
      stores suggests that it most likely decays due to depletion of Ca2+ in those
      stores. When caffeine was applied twice to a cell with only a brief (30 s)
      interval in between, the amount of Ca2+ released from stores was markedly
      diminished following the second caffeine application whereas the current carried
      in part by Ca2+ entry across the plasma membrane was not significantly affected.
      These and other studies described in the preceding paper indicate that activation
      of the nonselective cation plasma membrane channels in response to caffeine was
      not caused as a consequence of emptying of internal Ca2+ stores. Rather, it is
      proposed that caffeine activates these membrane channels either by direct
      interaction or alternatively by a linkage between ryanodine receptors on the
      sarcoplasmic reticulum and the nonselective cation channels on the surface
      membrane.

PMID- 7807056
TI  - How does ryanodine modify ion handling in the sheep cardiac sarcoplasmic
      reticulum Ca(2+)-release channel?
AB  - Under appropriate conditions, the interaction of the plant alkaloid ryanodine
      with a single cardiac sarcoplasmic reticulum Ca(2+)-release channel results in a
      profound modification of both channel gating and conduction. On modification, the
      channel undergoes a dramatic increase in open probability and a change in single
      channel conductance. In this paper we aim to provide a mechanistic framework for
      the interpretation of the altered conductance seen after ryanodine binding to the
      channel protein. To do this we have characterized single-channel conductance with
      representative members of three classes of permeant cation; group 1a monovalent
      cations, alkaline earth divalent cations, and organic monovalent cations. We have
      quantified the change in single-channel conductance induced by ryanodine and have
      expressed this as a fraction of conductance in the absence of ryanodine.
      Fractional conductance seen in symmetrical 210 mM solutions is not fixed but
      varies with the nature of the permeant cation. The group 1a monovalent cations
      (K+, Na+, Cs+, Li+) have values of fractional conductance in a narrow range (0.60
      0.66). With divalent cations fractional conductance is considerably lower (Ba2+,
      0.22 and Sr2+, 0.28), whereas values of fractional conductance vary considerably
      with the organic monovalent cations (ammonia 0.66, ethylamine 0.76, propanolamine
      0.65, diethanolamine 0.92, diethylamine 1.2). To establish the mechanisms
      governing these differences, we have monitored the affinity of the conduction
      pathway for, and the relative permeability of, representative cations in the
      ryanodine-modified channel. These parameters have been compared with those
      obtained in previous studies from this laboratory using the channel in the
      absence of ryanodine and have been modeled by modifying our existing single-ion,
      four-barrier three-well rate theory model of conduction in the unmodified
      channel. Our findings indicate that the high affinity, essentially irreversible,
      interaction of ryanodine with the cardiac sarcoplasmic reticulum Ca(2+)-release
      channel produces a conformational alteration of the protein which results in
      modified ion handling. We suggest that, on modification, the affinity of the
      channel for the group 1a monovalent cations is increased while the relative
      permeability of this class of cations remains essentially unaltered. The affinity
      of the conduction pathway for the alkaline earth divalent cations is also
      increased, however the relative permeability of this class of cations is reduced
      compared to the unmodified channel. The influence of modification on the handling
      by the channel of the organic monovalent cations is determined by both the size
      and the nature of the cation.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7807057
TI  - A conductance maximum observed in an inward-rectifier potassium channel.
AB  - One prediction of a multi-ion pore is that its conductance should reach a maximum
      and then begin to decrease as the concentration of permeant ion is raised equally
      on both sides of the membrane. A conductance maximum has been observed at the
      single-channel level in gramicidin and in a Ca(2+)-activated K+ channel at
      extremely high ion concentration (> 1,000 mM) (Hladky, S. B., and D. A. Haydon.
      1972. Biochimica et Biophysica Acta. 274:294-312; Eisenmam, G., J. Sandblom, and
      E. Neher. 1977. In Metal Ligand Interaction in Organic Chemistry and
      Biochemistry. 1-36; Finkelstein, P., and O. S. Andersen. 1981. Journal of
      Membrane Biology. 59:155-171; Villarroel, A., O. Alvarez, and G. Eisenman. 1988.
      Biophysical Journal. 53:259a. [Abstr.]). In the present study we examine the
      conductance-concentration relationship in an inward-rectifier K+ channel, ROMK1.
      Single channels, expressed in Xenopus oocytes, were studied using inside-out
      patch recording in the absence of internal Mg2+ to eliminate blockade of outward
      current. Potassium, at equal concentrations on both sides of the membrane, was
      varied from 10 to 1,000 mM. As K+ was raised from 10 mM, the conductance
      increased steeply and reached a maximum value (39 pS) at 300 mM. The single
      channel conductance then became progressively smaller as K+ was raised beyond 300
      mM. At 1000 mM K+, the conductance was reduced to approximately 75% of its
      maximum value. The shape of the conductance-concentration curve observed in the
      ROMK1 channel implies that it has multiple K(+)-occupied binding sites in its
      conduction pathway.

PMID- 7807058
TI  - Blockage of the light-sensitive conductance in hyperpolarizing photoreceptors of
      the scallop. Effects of tetraethylammonium and 4-aminopyridine.
AB  - The tight-seal whole-cell recording technique was used to examine the effect of
      tetraethylammonium (TEA) and 4-aminopyridine (4-AP) on the photocurrent of
      hyperpolarizing ciliary photoreceptors isolated from the distal retina of the bay
      scallop (Pecten irradians). In these cells, light causes an increase in a
      conductance that is highly selective to potassium ions. Extracellular application
      of TEA at a concentration of 50 mM produced a modest, reversible block
      (approximately 35% at -20 mV holding potential). The blockage was weakly voltage
      dependent, increasing by approximately 20% for a 20-mV hyperpolarization,
      suggestive of a site of interaction superficially located within the electric
      field of the membrane. Treatment with TEA produced no significant changes either
      in the light sensitivity of the photocurrent or in its kinetics. The effects of
      superfusion with 4-AP were more dramatic: the light-evoked current was nearly
      abolished (> 95%) at submillimolar concentrations, with a half-maximal dose of
      approximately 0.6 microns. The blockage had a rapid onset and was slowly
      reversible. No significant use or voltage dependency were observed. A number of
      control experiments indicated that the phototransduction cascade remained
      functional during treatment with 4-AP: the early receptor current, the prolonged
      after current and its suppression, the photoresponse kinetics and the light
      sensitivity of the cell were little affected by 4-AP, suggesting that the
      suppression of the photocurrent is due to blockage of the light-sensitive
      channels, rather than impairment of some of the activation steps. The results are
      discussed in the light of a possible kinship between the light-activated
      potassium channels of invertebrate hyperpolarizing photoreceptors and the family
      of rapidly-inactivating voltage-dependent potassium channels, which typically
      exhibit high susceptibility to blockage by this drug.

PMID- 7807059
TI  - Internal block of human heart sodium channels by symmetrical tetra
      alkylammoniums.
AB  - The human heart Na channel (hH1) was expressed by transient transfection in
      tsA201 cells, and we examined the block of Na current by a series of symmetrical
      tetra-alkylammonium cations: tetramethylammonium (TMA), tetraethylammonium (TEA),
      tetrapropylammonium (TPrA), tetrabutylammonium (TBA), and tetrapentylammonium
      (TPeA). Internal TEA and TBA reduce single-channel current amplitudes while
      having little effect on single channel open times. The reduction in current
      amplitude is greater at more depolarized membrane potentials. Analysis of the
      voltage-dependence of single-channel current block indicates that TEA, TPrA and
      TBA traverse a fraction of 0.39, 0.52, and 0.46 of the membrane electric field to
      reach their binding sites. Rank potency determined from single-channel
      experiments indicates that block increases with the lengths of the alkyl side
      chains (TBA > TPrA > TEA > TMA). Internal TMA, TEA, TPrA, and TBA also reduce
      whole-cell Na currents in a voltage-dependent fashion with increasing block at
      more depolarized voltages, consistent with each compound binding to a site at a
      fractional distance of 0.43 within the membrane electric field. The
      correspondence between the voltage dependence of the block of single-channel and
      macroscopic currents indicates that the blockers do not distinguish open from
      closed channels. In support of this idea TPrA has no effect on deactivation
      kinetics, and therefore does not interfere with the closing of the activation
      gates. At concentrations that substantially reduce Na channel currents, TMA, TEA,
      and TPrA do not alter the rate of macroscopic current inactivation over a wide
      range of voltages (-50 to +80 mV). Our data suggest that TMA, TEA, and TPrA bind
      to a common site deep within the pore and block ion transport by a fast-block
      mechanism without affecting either activation or inactivation. By contrast,
      internal TBA and TPeA increase the apparent rate of inactivation of macroscopic
      currents, suggestive of a block with slower kinetics.

PMID- 7807060
TI  - Evidence for a direct interaction between internal tetra-alkylammonium cations
      and the inactivation gate of cardiac sodium channels.
AB  - The effects of internal tetrabutylammonium (TBA) and tetrapentylammonium (TPeA)
      were studied on human cardiac sodium channels (hH1) expressed in a mammalian
      tsA201 cell line. Outward currents were measured at positive voltages using a
      reversed Na gradient. TBA and TPeA cause a concentration-dependent increase in
      the apparent rate of macroscopic Na current inactivation in response to step
      depolarizations. At TPeA concentrations < 50 microM the current decay is well fit
      by a single exponential over a wide voltage range. At higher concentrations a
      second exponential component is observed, with the fast component being dominant.
      The blocking and unblocking rate constants of TPeA were estimated from these
      data, using a three-state kinetic model, and were found to be voltage dependent.
      The apparent inhibition constant at 0 mV is 9.8 microM, and the blocking site is
      located 41 +/- 3% of the way into the membrane field from the cytoplasmic side of
      the channel. Raising the external Na concentration from 10 to 100 mM reduces the
      TPeA-modified inactivation rates, consistent with a mechanism in which external
      Na ions displace TPeA from its binding site within the pore. TBA (500 microM) and
      TPeA (20 microM) induce a use-dependent block of Na channels characterized by a
      progressive, reversible, decrease in current amplitude in response to trains of
      depolarizing pulses delivered at 1-s intervals. Tetrapropylammonium (TPrA), a
      related symmetrical tetra-alkylammonium (TAA), blocks Na currents but does not
      alter inactivation (O'Leary, M. E., and R. Horn. 1994. Journal of General
      Physiology. 104:507-522.) or show use dependence. Internal TPrA antagonizes both
      the TPeA-induced increase in the apparent inactivation rate and the use
      dependence, suggesting that all TAA compounds share a common binding site in the
      pore. A channel blocked by TBA or TPeA inactivates at nearly the normal rate, but
      recovers slowly from inactivation, suggesting that TBA or TPeA in the blocking
      site can interact directly with a cytoplasmic inactivation gate.

PMID- 7807061
TI  - Modulation of synaptic transfer between retinal cones and horizontal cells by
      spatial contrast.
AB  - We studied the influence of steady annular light on the kinetics and sensitivity
      of horizontal cell (HC) responses to modulation of the intensity of small
      concentric spots in the turtle retina. As shown by previous investigators, when
      the intensity of the annulus was equal to the mean spot intensity, spot response
      kinetics were the same as those for the modulation of spatially uniform light.
      Turning off the annulus attenuated dramatically high-frequency flicker
      sensitivity and enhanced somewhat low-frequency sensitivity. This phenomenon
      reflects a modulation of synaptic transfer between cones and second-order neurons
      that is mediated by cones, and it will be referred to as cone-mediated surround
      enhancement (CMSE). Our main results are as follows: (a) The change in test-spot
      response sensitivity and kinetics upon dimming a steady surrounding annulus is a
      consequence of the change in spatial contrast rather than change in overall light
      level. (b) Introduction of moderate contrast between the mean spot intensity and
      steady surrounding light intensity causes a marked change in spot response
      kinetics. (c) The dependence of spot response kinetics on surrounding light can
      be described by a phenomenological model in which the steady state gain and the
      time constant of one or two single-stage, low-pass filters increase with
      decreasing annular light intensity (d) The effect of surrounding light on spot
      responses of a given HC is not determined by change in the steady component of
      the membrane potential of that cell. (e) Light outside the receptive field of an
      HC can affect that cell's spot response kinetics. (f) In an expanding annulus
      experiment, the distance over which steady annular light affects spot response
      kinetics varies among HCs and can be quite different even between two cells with
      closely matched receptive field sizes. (g) The degree of CMSE is correlated with
      HC receptive field size. This correlation suggests that part of the enhancement
      mechanism is located in the HC. Taken together, our results suggest the
      involvement of the inner retina in CMSE.

PMID- 7807062
TI  - Contrast gain, signal-to-noise ratio, and linearity in light-adapted blowfly
      photoreceptors.
AB  - Response properties of short-type (R1-6) photoreceptors of the blowfly
      (Calliphora vicina) were investigated with intracellular recordings using
      repeated sequences of pseudorandomly modulated light contrast stimuli at adapting
      backgrounds covering 5 log intensity units. The resulting voltage responses were
      used to determine the effects of adaptational regulation on signal-to-noise
      ratios (SNR), signal induced noise, contrast gain, linearity and the dead time in
      phototransduction. In light adaptation the SNR of the photoreceptors improved
      more than 100-fold due to (a) increased photoreceptor voltage responses to a
      contrast stimulus and (b) reduction of voltage noise at high intensity
      backgrounds. In the frequency domain the SNR was attenuated in low frequencies
      with an increase in the middle and high frequency ranges. A pseudorandom contrast
      stimulus by itself did not produce any additional noise. The contrast gain of the
      photoreceptor frequency responses increased with mean illumination and the gain
      was best fitted with a model consisting of two second order and one double pole
      of first order. The coherence function (a normalized measure of linearity and
      SNR) of the frequency responses demonstrated that the photoreceptors responded
      linearly (from 1 to 150 Hz) to the contrast stimuli even under fairly dim
      conditions. The theoretically derived and the recorded phase functions were used
      to calculate phototransduction dead time, which decreased in light adaptation
      from approximately 5-2.5 ms. This analysis suggests that the ability of fly
      photoreceptors to maintain linear performance under dynamic stimulation
      conditions results from the high early gain followed by delayed compressive feed
      back mechanisms.

PMID- 7807063
TI  - Gender differences in hostility among depressed and medical outpatients.
AB  - We assessed possible gender differences in state and trait hostility in a large
      sample of depressed outpatients and in a group of medical outpatients. We
      administered the Cook and Medley Hostility Scale, measuring trait hostility and
      aggressiveness, and the Symptom Questionnaire, including a state measure of
      irritability and hostility, to 218 depressed outpatients and 51 medical
      outpatients. There was a statistically significant positive correlation between
      severity of depression and our state measure of hostility, and a weak, although
      statistically significant, relationship between severity of depression and total
      score of our trait measure of hostility. Among depressed outpatients, trait
      hostility was greater in men than in women, while no significant gender
      difference was observed in state hostility. Among medical outpatients, the state
      hostility scale scores were significantly higher in men than in women. These
      gender differences in both groups remained significant even after adjusting for
      severity of depression. Thus, it appears that men with depression tend to have
      higher scores than women on state and trait measures of hostility, suggesting
      that men may be at greater risk than women of developing patterns of pathologic
      aggression and hostile behavior.

PMID- 7807064
TI  - Somatization. Concepts, data, and predictions from the high risk model of threat
      perception.
AB  - Eighty-three consecutive patients with chronic somatic complaints seen prior to
      therapy were tested on the eight factors of the High Risk Model of Threat
      Perception. Thirty-two percent were high and 28% were low on hypnotic ability,
      which is more highs and lows than would be expected in a normal population. In
      the high and low hypnotic ability somatizers, the distribution of somatic and
      psychological symptoms is significantly different from the moderate group.
      Counterintuitively, hypnotic ability and major life change were orthogonal to all
      of the other risk factors. These findings are consistent with eight of nine
      predictions from the High Risk Model of Threat Perception.

PMID- 7807065
TI  - Depression and posttraumatic stress disorder among a community sample of
      adolescent and young adult Afghan refugees.
AB  - This study was designed to determine the prevalence of posttraumatic stress
      disorder (PTSD) and other psychiatric disorders among a community sample of
      adolescent and young adult refugees from Afghanistan. The study also measured the
      correlation of their current psychiatric disorders with the number of traumatic
      events experienced, parental acculturation and distress, and other important
      demographic factors. Thirty-eight refugees between 12 and 24 years of age were
      interviewed with the Structured Clinical Interview for DSM-III-R. Five subjects
      met DSM-III-R criteria for PTSD, 11 subjects met the criteria for major
      depression, and 13 had either PTSD or major depression or both. Significant
      positive correlations were found between the subjects' psychiatric diagnosis and
      the total number of traumatic events experienced and the parental level of
      psychological distress (especially maternal distress). There were negative
      correlations between children's symptomatology and a measure of maternal
      acculturation. These results suggest that a significant proportion of adolescent
      and young adult Afghan refugees in the community suffer from severe but
      undiagnosed psychiatric disorders.

PMID- 7807066
TI  - Sinister psychotics. Left-handedness in schizophrenia and affective disorder.
AB  - The notion persists that psychotics, particularly schizophrenics, are less right
      handed than the general population, and that this deviation is
      pathophysiologically important in some patients. We assessed handedness and
      psychopathology in 163 DSM-III schizophrenics, 103 affectives, and 112 normal
      subjects. Although schizophrenics were less right-handed than normal subjects,
      this difference was primarily due to more mixed handedness among
      schizoaffectives. Relationships between handedness and specific psychopathology
      were uninformative, and we conclude that handedness may not be an important
      consideration in the study of psychosis.

PMID- 7807067
TI  - The relationship between types of anxiety and depression.
AB  - There has been considerable debate about the relationship between anxiety and
      depression. Most of the research in this area has examined relationships between
      composite indices of each construct. It has been suggested, however, that social
      anxiety may be more highly related to depression than are other forms of anxiety.
      We report the results of a study of the differential relationship of anxiety
      related to three sources (social evaluation, physical danger, and unfamiliar
      situations) to both self-report and clinician-rated levels of depression in a
      sample of 117 psychiatric outpatients. The results indicate that anxiety
      concerning social evaluation and unfamiliar situations was more highly related to
      depression than anxiety about physical danger.

PMID- 7807068
TI  - Longitudinal assessment of posttraumatic stress disorder and depression after
      exposure to traumatic death.
AB  - Little is known of the specific effects of exposure to traumatic death, an
      important dimension of many disasters. This study examined acute and long-term
      intrusive and avoidant symptoms, depression, and posttraumatic stress disorder
      (PTSD) in disaster workers exposed to traumatic death after the USS Iowa gun
      turret explosion. Fifty-four volunteer body handlers were assessed at 1, 4, and
      13 months. They were compared with 11 non-body handler disaster worker
      volunteers. The Impact of Events Scale, Zung Depression Scale, Symptom Checklist
      90-Revised, and a multi-method assessment of PTSD were used. Intrusive and
      avoidant symptoms were elevated at 1, 4, and 13 months, and decreased over time.
      Probable PTSD was present in 11% at 1 month, 10% at 4 months, and 2% at 13
      months. The frequency of depression was not increased. Single body handler
      disaster workers reported more avoidance (times 1 and 2) and somatization (time
      1) than did married workers. Body handlers reported more intrusion, avoidance,
      hostility, and somatization at 1 month than did non-body handler volunteers.
      These results indicate that exposure to traumatic death increases intrusive and
      avoidant symptoms, hostility, somatization, and the risk of PTSD and that
      symptoms can persist for months.

PMID- 7807069
TI  - The relationship between age and personality disorders in depressed outpatients.

PMID- 7807070
TI  - Psychiatric morbidity in narcoleptics on chronic high dose methylphenidate
      therapy.

PMID- 7807071
TI  - A systematic assessment of tricyclic antidepressants in the treatment of adult
      attention-deficit hyperactivity disorder.

PMID- 7807072
TI  - Comparison of psychological symptoms between drug abusers seeking and not seeking
      treatment.

PMID- 7807073
TI  - Selected Minnesota Multiphasic Personality Inventory-2 scales for identifying
      women with a history of sexual abuse.

PMID- 7807074
TI  - Dispersal and survival of Aedes albopictus at a scrap tire yard in Missouri.
AB  - Field-reared Aedes albopictus were marked with fluorescent pigment upon release
      and recaptured with a vacuum aspirator at a scrap tire yard and in surrounding
      vegetation in Potosi, MO, during 1989-90. In 8 dispersal trials, 8.1%
      (1,100/13,513) of the Ae. albopictus were recaptured with 84.4% (928/1,100)
      collected in the forest edge ecotone between 10 and 600 m from the release point.
      The maximum dispersal distance recorded was 525 m and 11.1% (122/1,100) dispersed
      further than 100 m. In 3 survival trials, 4.8% (2,660/55,284) of the mosquitoes
      were recaptured. Adult Ae. albopictus females survived an average of 8.2 days
      (probability of daily survival [PDS] = 0.89, range = 0-24) and males an average
      of 3.9 days (PDS = 0.77, range = 0-12). The dispersal and survival capacity of
      Ae. albopictus adults may contribute to the spread and potential health threat of
      this mosquito in the USA.

PMID- 7807076
TI  - Intradomicillary pre- and postfeeding behavior of Anopheles pseudopunctipennis of
      southern Mexico: implications for malaria control.
AB  - The intradomicillary pre- and postfeed resting behavior of Anopheles
      pseudopunctipennis was studied in an experimental house in southern Mexico.
      During resting periods (both pre-/postfeed) mosquitos had greater contact
      (landings) with the inner roof than with the walls and other surfaces. A
      comparison of mean landing frequency and overall resting time (pre-/postfeed)
      showed that a greater periodic and prolonged contact occurred prefeed, probably
      as a result of disturbed activity associated with host movements. Pre-/postfeed
      resting patterns on walls were limited to a 0.6-0.5-m-wide band, nearly 1 m from
      the floor, and to a narrower band on the roof, 0.3-0.2 m wide, approximately 2.3
      m from the floor, respectively. We calculated that with a band width of 0.8 m on
      the walls and another band 0.8 m wide on the roof, 87.2% of the mosquitoes had at
      least one contact with either the wall, the roof, or with both surfaces, along
      with an overall mean resting time (pre-/postfeed) of 8.1 min/landing. These
      findings suggest that a high potential for control can be achieved by spraying
      preferred wall and roof resting sites in this region where the intradomicillary
      application of residual insecticide is the primary malaria control measure.

PMID- 7807075
TI  - Utilization of bloodfed females of Aedes aegypti as a vehicle for the transfer of
      the insect growth regulator pyriproxyfen to larval habitats.
AB  - Bloodfed female Aedes aegypti were exposed to a surface treated with pyriproxyfen
      at 1.0 g m2 for 30 min and then allowed to lay eggs in cups of water containing
      4th-instar larvae. Adult emergence from the immatures was highly inhibited, and
      transmission of pyriproxyfen from the females to the water was revealed. The
      transfer of the chemical to the water decreased with time before the blood meal.
      Chemical analysis for pyriproxyfen on the exoskeleton of treated females
      demonstrated the rapid disappearance of the compound. Pyriproxyfen obviously
      affected egg maturation of females treated before blood meals, as the number of
      eggs deposited decreased concurrently with the number of days before the blood
      meals.

PMID- 7807077
TI  - Peri-/intradomicillary behavior in relation to host-seeking of Anopheles
      pseudopunctipennis in southern Mexico.
AB  - Peri-/intradomicillary resting and host-seeking behavior of Anopheles
      pseudopunctipennis was studied in an experimental house (surrounded by a curtain
      net) that had not been sprayed with insecticide. Peak mosquito densities were
      recorded resting on vegetation 1 h earlier (1900-2000 h) than on the curtain-net,
      suggesting that a proportion of females prefer resting on adjacent vegetation
      prior to moving indoors. Between 2000 and 2100 h there was a marked decrease in
      numbers of mosquitoes resting on the exterior of the curtain-net. In separate
      experiments without the net, a single peak in numbers of mosquitoes resting on
      interior surfaces and/or biting human bait occurred between 2000 and 2100 h.
      Unfed mosquitoes had higher numbers of contacts with wall surfaces than with the
      roof. Moreover, a higher proportion of mosquitoes collected on human bait had >
      or = 1 dilatation(s), and higher parity rates than those resting on walls. Higher
      proportions of parous mosquitoes more frequently fed from 1800 to 2100 h, whereas
      higher proportions of nulliparous mosquitoes fed during morning hours. Nearly 25%
      of all mosquitoes exited 1 h following their release inside the house, whereas
      nearly 7% remained indoors for > 9 h. Overall results demonstrated that the
      behavior of An. pseudopunctipennis females depends on outdoor/indoor stimuli,
      being multivariable in nature. This includes contacts with a variety of
      biological (i.e., vegetation, human) and inert surfaces, which in part appears to
      be controlled by age structure.

PMID- 7807078
TI  - Integrated management of waste tire mosquitoes utilizing Mesocyclops longisetus
      (Copepoda: Cyclopidae), Bacillus thuringiensis var. israelensis, Bacillus
      sphaericus, and methoprene.
AB  - This study evaluated the compatibility and efficacy of using a predatory copepod,
      Mesocyclops longisetus in concert with 3 "biorational" compounds for mosquito
      control in waste tires. The toxicity of Bacillus thuringiensis var. israelensis
      (B.t.i), Bacillus sphaericus, and methoprene to Mesocyclops longisetus was
      assessed in the laboratory using concentrations 10 times the maximum labeled or
      suggested rate and based on a water depth of 7.6 cm. Microbials were tested using
      mature copepods exposed for durations of 24, 48, and 72 h. Methoprene bioassays
      consisted of individually exposing newly hatched copepods (i.e., nauplius larvae)
      and monitoring their development to maturity. The toxicity tests indicated
      B.t.i., B. sphaericus, and methoprene were not deleterious to copepods at
      concentrations exceeding those expected in the field. Copepods exposed to
      methoprene matured normally, and when mated, 50% developed egg sacs. A 5-month
      field test, integrating the copepod and B.t.i., B. sphaericus, and methoprene
      provided better mosquito reduction together than either copepods or control
      agents alone. When copepods were combined with B.t.i. or methoprene, overall
      reduction of 3rd- and 4th-instar larvae during the 5-month interval was equal to
      or greater than 90%. Bacillus thuringiensis var. israelensis alone temporarily
      produced a high degree of larval reduction (up to 100%), however reapplications
      were necessary to maintain that level of control. Of all the treatments, B.
      sphaericus alone produced the lowest degree of mosquito suppression due to lack
      of toxicity to Aedes albopictus, the predominant species during the study. It is
      recommended that mosquito control managers consider integrating M. longisetus and
      B.t.i. or methoprene against mosquitoes in waste tires.

PMID- 7807079
TI  - Interaction of the Culex quinquefasciatus egg raft pheromone with a natural
      chemical associated with oviposition sites.
AB  - In laboratory bioassays, gravid Culex quinquefasciatus mosquitoes were strongly
      attracted and or stimulated to oviposit by a habitat-derived chemical cue, 3
      methylindole, at several concentrations ranging from 0.01 to 1 microgram/liter in
      water. At concentrations above 10 micrograms/liter, 3-methylindole became
      repellent or deterrent. Responses to the known egg raft pheromone, 6-acetoxy-5
      hexadecanolide, were much weaker and were relatively constant above a threshold
      dosage of about 0.1 microgram. Responses to blends of a fixed amount of the
      pheromone with variable doses of 3-methylindole were shown to be additive rather
      than synergistic.

PMID- 7807080
TI  - Do fish repel oviposition by Aedes taeniorhynchus?
AB  - We tested the hypothesis that fish indirectly control mosquitoes by repelling
      oviposition. Aedes taeniorhynchus oviposition in mangrove forests, natural pools,
      and excavated pools with different concentrations of fish was compared.
      Oviposition in adjacent mangrove forests was concentrated in the site with the
      lowest fish density. In 3 mangrove forests, egg populations from pool banks were
      significantly (P < 0.001) lower for pools with fish than for fishless pools, with
      an overall mean +/- SD of 1.6 +/- 5.7 and 20.0 +/- 34.8 eggs/sample,
      respectively. At one pool, egg densities increased significantly (P < 0.001) from
      0.36 to 5.00 eggs/sample after drying killed fish. In excavated pools,
      oviposition was significantly (P < 0.001) affected by fish. These data indicate
      that Ae. taeniorhynchus avoids ovipositing in sites with high concentrations of
      fish and suggest that the response is fish-mediated. This behavior may help to
      explain the migratory habits and population dynamics of Ae. taeniorhynchus.

PMID- 7807081
TI  - Laboratory evaluation of fenitrothion microcapsules as a new residual spraying
      formulation for mosquito control.
AB  - Physicochemical and insecticidal properties of fenitrothion microcapsule (MC) as
      a new residual spraying formulation for mosquito control were studied. The wall
      staining after treatment with MC at the rate of 1-2 g AI/m2 was not noticeable as
      compared with that of wettable powder (WP). Covering rate with MC on a vertical
      wall was almost the same as WP and emulsifiable concentrate (EC) when the wall
      material was absorptive plywood and mud, and was relatively higher than WP and EC
      when the wall material was nonabsorptive overlaid plywood. Residual efficacy of
      MC at the rate of 1 g/m2 was almost equivalent or superior to that of WP at the
      rate of 2 g/m2. Fenitrothion MC also has had an "airborne" effect, which is sort
      of a vapor killing effect of insecticides under high vapor pressure. This
      suggested a difference in mode of action in mosquitoes from that for cockroach
      control.

PMID- 7807082
TI  - Quantitative sampling of immature Aedes aegypti in metal drums using sweep net
      and dipping methods.
AB  - The behavior of aquatic stages of Aedes aegypti was evaluated in 200-liter metal
      drums to develop improved surveillance. When known numbers of larvae recovered
      with a rectangular net and with a standard dipper were compared, all stages
      except 1st instar were most numerous in the top 1/3 of the drum. Water
      temperature was the only significant variable affecting the vertical distribution
      of 4th-instar larvae; light intensity and pH were nonsignificant factors. Rust in
      the water was also thought to influence distribution towards the surface layer.
      When 100-400 immatures were released into a full drum, immatures were detected by
      sweeping and dipping the surface layer on 93.3 and 72.9% of trials, respectively.
      The correlation coefficients (r) of recoveries of known numbers of immatures by
      sweeping and dipping varied from 0.92 to 0.98 and from 0.38 to 0.89,
      respectively. The coefficients of variation were 2-5 times smaller for sweeping
      than for dipping. Recoveries from dipping were shown to be affected by the water
      volume in the drum. Counts of 4th-instar larvae from one sweep around the top are
      sufficient to assess productivity in drums.

PMID- 7807083
TI  - Aedes albopictus distribution, abundance, and colonization in Lee County,
      Florida, and its effect on Aedes aegypti.
AB  - In 1992 the known southern limit of Aedes albopictus in Florida was in Lee
      County. Through oviposition surveillance, the distribution of Ae. albopictus was
      determined, and its frequency relative to Aedes aegypti and colonization pattern
      of areas previously occupied by Ae. aegypti were examined in Lee County. The data
      collected in the first year of surveillance demonstrate the ability of Ae.
      albopictus to rapidly and preferentially colonize large expanses of rural
      southwest Florida. Urban and suburban areas of the county showed slower
      colonization rates. In suburban areas, Ae. albopictus became the dominant
      container-breeding mosquito species, whereas it did not become dominant in urban
      areas. During the study period, Ae. albopictus did not displace Ae. aegypti in
      urban or suburban habitats. The southern limit of Ae. albopictus moved a distance
      of 8.1 km (5 mi.) in 6 wk to the southern border of the county.

PMID- 7807084
TI  - Emergency control of Aedes aegypti in the Dominican Republic using the Scorpion
      20 ULV forced-air generator.
AB  - In an effort to develop a more effective measure for use in emergency control of
      the dengue vector Aedes aegypti. applications of a combination of a larvicide
      (Bacillus thuringiensis israelensis [B.t.i.]) and an adulticide (permethrin) were
      made using a truck-mounted forced-air generator (Scorpion 20) and evaluated in
      the Dominican Republic. This method has the potential to simultaneously control
      adults and larvae. In bioassay cages placed in household water containers at the
      time of application, larval mortalities were 95.1 and 100% for 2 application
      rates of permethrin mixed with B.t.i. Adult mortalities were not as impressive,
      probably because of resistance to permethrin. Higher adult mortality in caged
      specimens (78.5%) and a substantial reduction in the natural population (68.4%)
      of Ae. aegypti were obtained following a 2.1-g AI/ha application of deltamethrin
      alone.

PMID- 7807085
TI  - Evaluation of aerial and ground-applied adulticides against mosquito species in
      Arkansas and Louisiana.
AB  - Mosquitoes were subjected to ultra-low volume (ULV) aerial applications of
      permethrin synergized with piperonyl butoxide (Biomist 30:30. Biomist 31:66) and
      Cythion and ULV ground applications of permethrin synergized with piperonyl
      butoxide (Biomist 30:30. Biomist 12:60), resmethrin (Scourge), and sumithrin
      (Solo 40-OS and Duets 8.8-OS). Permethrin compounds tested aerially against
      Anopheles quadrimaculatus were not significantly different. Biomist 30:30 tested
      aerially against Culex quinquefasciatus did provide significantly greater
      mortality compared to Cythion. Biomist 30:30 and Biomist 31:66 tested aerially
      against An. quadrimaculatus at 1 h did not provide a significant difference up to
      600 ft. (182.9 m). Both products ground tested at 24 h revealed nonsignificant
      results. Biomist 30:30 and Biomist 12:60 ground tested against Cx.
      quinquefasciatus at 1 h did not provide a significant difference at 100 ft. (30.5
      m) or 200 ft. (61.0 m); however, significantly greater mortality was observed at
      300 ft. (61.0 m) and 600 ft. (91.4 m). At 24 h no significant mortality
      differences were observed at 300 ft. (61.0 m) and 600 ft. (91.4 m). Anopheles
      quadrimaculatus and Psorophora columbiae were treated with a 1:1 mixture of Solo
      40-OS and Duet 8.8-OS (sumithrin+piperonyl butoxide). Significant mortality
      differences (P < or = 0.05) between species at 1 h posttreatment occurred at 300
      ft. (91.4 m).

PMID- 7807086
TI  - Seasonality, prevalence and pathogenicity of the gregarine Ascogregarina
      taiwanensis (Apicomplexa: Lecudinidae) in mosquitoes from Florida.
AB  - Aedes albopictus larvae collected in Gainesville, FL, were infected with the
      gregarine Ascogregarina taiwanensis. Natural prevalence varied from 68 to 100%.
      Eight mosquito species were tested in the laboratory for susceptibility to A.
      taiwanensis isolated from field-collected Ae. albopictus. Aedes aegypti, Aedes
      albopictus, and Aedes taeniorhynchus became 100% infected in the larval stage,
      whereas Aedes triseriatus was less susceptible; Culex quinquefasciatus, Culex
      nigripalpus, Culex territans, and Anopheles quadrimaculatus were not susceptible.
      Viable A. taiwanensis oocysts from adults were recovered from Ae. taeniorhynchus
      (30%) and Ae. albopictus (100%); no oocysts were produced in the other exposed
      hosts. Mortality induced by A. taiwanensis infection was low in all mosquitoes
      except Ae. taeniorhynchus. We conclude that A. taiwanensis has little short-term
      impact on the mortality of the 3 most common container-inhabiting mosquito
      species in Florida; however, the long-term impact on overall host population
      regulation has yet to be determined.

PMID- 7807087
TI  - Immunodetection of Plasmodium falciparum zygotes and ookinetes in Anopheles blood
      meals.
AB  - An indirect fluorescent antibody assay (IFA) using monoclonal antibodies to the
      25-kDa Plasmodium falciparum ookinete surface antigen was developed to detect and
      quantify preoocyst stages of P. falciparum in mosquito blood meals. This IFA is
      suitable for the detection and quantitation of zygotes/macrogametes, retorts
      (immature ookinetes), and ookinetes. Time-course evaluations showed that zygotes
      represented > 52% of the parasites detected between 6 and 24 h. From 24 to 36 h
      similar densities of all 3 stages were observed. By 42 h. 56% of the detectable
      parasites were ookinetes. Compared to the hemocytometer the IFA provided a better
      estimate of stage-specific infection rates and densities. The assay is a useful
      new tool for evaluating preoocyst stages in laboratory-infected mosquitoes and
      has the potential for detecting natural infections in vector populations.

PMID- 7807088
TI  - Influence of human breath on selection of biting sites by Anopheles albimanus.
AB  - The selection of biting sites by Anopheles albimanus on a human host was studied
      in the laboratory. The perception of exhaled breath guided the mosquitoes towards
      the head region, and was associated with a preference (P < 0.001) for biting this
      part of the body. Subsequent removal of breath resulted in a strong reduction of
      the number of bites on the head (from 49 to 20%). The significance of these
      findings in relation to host location is discussed.

PMID- 7807089
TI  - Use of a modified chemical transfer pump for sampling Culiseta melanura larvae.
AB  - The cryptic nature of Culiseta melanura larval habitats has limited the use of
      the conventional one-pint dipper for enumerating the larval density of this
      species. A modified chemical transfer pump was used in a survey of a known
      breeding swamp. Field trials assessed the practicality and potential biases
      towards instars in open vs. closed crypts. From 148 samples taken at 37 sites,
      631 Cs. melanura larvae were collected. Closed crypts accounted for 21% of the
      positive samples. The pump had utility in the field but a relative scarcity of
      4th-instar larvae in the samples may indicate a source of bias toward younger
      instars.

PMID- 7807090
TI  - Trophic status, oogenic stages, and insemination of resting populations of three
      Simulium species (Diptera: Simuliidae) in Chiapas, Mexico.
AB  - Of 176 black fly females collected resting at the edge of El Rosario River, 77%
      were caught in rocky shelters, whereas the others were captured on damp stretches
      of river bank. Simulium ochraceum predominated in the catches (74%), followed by
      Simulium metallicum (21%), and Simulium callidum (5%). Percentages of females
      without blood in their gut were 70, 85, and 67%, respectively. Of 55 S. ochraceum
      females that had recently oviposited (sacculate), 29 had the remains of a blood
      meal in the gut. Of 64 nulliparous females, 48 exhibited early oogenesis
      (Christopher's stage I-II) indicating recent emergence. At Las Golondrinas
      village, 36% (71) of 199 specimens were S. ochraceum, of these 85% had no blood
      in the midgut. Five females of S. ochraceum at this locality had red blood and 6
      had black blood in their gut. Of 43 parous and 28 nulliparous females, 36 and 25
      had ovaries at stages I-II, respectively. Most females of S. metallicum had no
      blood in their gut (92%). Nullipars were abundant (91) and stage N (24 h old) was
      observed in 66 of them.

PMID- 7807091
TI  - A convenient mosquito membrane feeding system.
AB  - A convenient, electronically controlled, in situ, membrane feeding system is
      described. Evaluation of the system for feeding single pair-mated Aedes aegypti
      with defibrinated, refrigerated pig blood indicated no significant difference
      from mouse-fed controls in rat of egg maturation, fecundity, or pupal yield. The
      feeding system is also suitable for use with substitute protein meals.

PMID- 7807092
TI  - Assessment of Anopheles quadrimaculatus response to permethrin and resmethrin by
      topical application.
AB  - Topical applications with field-captured mosquitoes provided LD50 estimates
      ranging from 13.3 to 20.0 ppm for permethrin and 8.5 to 18.9 ppm for resmethrin
      in the Stuttgart, AR, area in 1993. Mosquitoes collected from the abatement area
      appeared to be more susceptible to resmethrin than those from outside the area
      (8.5 ppm vs. 18.9 ppm). The observed difference was not great enough to be of
      concern from an economic or control standpoint. The data provided a firm baseline
      for future assessment of changes in susceptibility to these 2 materials.
      Mosquitoes collected in Walnut Ridge, AR, were susceptible to permethrin and
      resmethrin within the same range as the Stuttgart populations, but the limited
      number of observations preclude firm LD50 estimates.

PMID- 7807093
TI  - Laboratory studies of desiccation resistance in Mesocyclops (Copepoda:
      Cyclopoida).
AB  - The desiccation resistance of 4 species of Mesocyclops from varied geographical
      locations was tested against water content in sediment, temperature, and
      photoperiod. Trays containing sediment were inoculated with copepods and allowed
      to dry out for a period of 2 months and then reflooded. Both copepodids and
      adults of all species tested displayed desiccation resistance, with water content
      having greatest effect on survival.

PMID- 7807094
TI  - Blood hosts of Aedes albopictus in the United States.
AB  - Bloodfed Aedes albopictus were collected during 1989-91 by vacuum aspirator from
      rural and urban study sites in Missouri, Florida, Indiana, Illinois, and
      Louisiana. Blood hosts identified by ELISA and precipitin tests were rabbit (n =
      91), Rattus sp. (n = 69), dog (n = 14), unidentified mammal (n = 14), cow (n =
      13), human (n = 10), deer (n = 10), sciurid (n = 7), turtle (n = 5), murid other
      than Rattus sp. (n = 4), raccoon (n = 3), passeriform bird (n = 3), and cat (n =
      2). As an opportunistic bloodfeeder, Ae. albopictus may be a potential vector of
      domestic arboviruses and a nuisance pest where infestations occur.

PMID- 7807095
TI  - Pilot scale production and application in wildlife ponds of Lagenidium giganteum
      (Oomycetes: Lagenidiales).
AB  - Lagenidium giganteum, a facultative parasite of mosquito larvae, has recently
      been registered by the U.S. Environmental Protection Agency for operational
      mosquito control. We report here the first pilot scale production of the mycelium
      formulation. Scale-up from 10 to 650 liters was accomplished by a proportionate
      increase of medium components and volume of water. Foaming of the culture medium
      had not been encountered previously, but was a serious problem in pilot scale
      production due to the very rapid growth of a large volume of L. giganteum.
      Addition of an antifoaming agent did not adversely affect growth, but reduced the
      ability of the fungus to sporulate. Despite what was effectively a 100-fold
      reduction in the desired application rate due to reduced sporulation, L.
      giganteum infected sentinel mosquito larvae and reduced field populations for
      more than 2 months following application.

PMID- 7807097
TI  - Field studies on populations of Aedes albopictus and Toxorhynchites species in
      bamboo pots in Malaysia.
AB  - Between April 1987 and March 1988, populations of immature Aedes albopictus and
      Toxorhynchites spp. in bamboo pots were sampled weekly. Populations of Ae.
      albopictus and rainfall varied from month to month. During the heavy rainfall
      months of September and October 1987, larval counts of Ae. albopictus were high,
      between 30.8 and 49.2 larvae per week compared to 16 larvae per week during the
      low rainfall month of January 1988. A higher population of Toxorhynchites spp.
      was associated with a low population of the vector.

PMID- 7807096
TI  - New techniques for rearing black flies from pupae (Diptera: Simuliidae).
AB  - Simple techniques are described for collecting black fly pupae from streams using
      plastic strips and for rearing large numbers of adult black flies in inexpensive
      enclosures made of chicken wire and cloth mesh netting, and 2 methods are
      described for rearing adult black flies individually from pupae. The first method
      of rearing individual black flies uses 1.5-ml microcentrifuge tubules and the
      second uses easy-to-construct rearing chambers that provide moisture for the
      developing pupa and water for the adult to imbibe. Instructions for assembly are
      provided. Specimens obtained using these rearing chambers are of museum quality.

PMID- 7807098
TI  - First record of Culiseta morsitans from Wyoming.

PMID- 7807099
TI  - Presence of Culicoides imicola (Diptera: Ceratopogonidae) in Jaen, Spain.
AB  - Culicoides imicola Kieffer is reported from 2 locations in the province of Jaen,
      Spain. The locations are outside the area where African horse sickness epizootics
      occurred from 1988 to 1990. The absence of African horse sickness in Jaen during
      this period may have been due to the low abundance of this species.

PMID- 7807100
TI  - Presentation of the John N. Belkin Award to Thomas Henry Gardiner Aitken.

PMID- 7807101
TI  - Long-term results of cemented total hip arthroplasty in patients 45 years old or
      younger. A 16-year follow-up study.
AB  - Forty-nine cemented total hip arthroplasties in patients younger than 45 years
      were reviewed, with an average follow-up period of 16.2 years. The results were
      compared with the same group previously reported at average follow-up periods of
      4.5 and 9.2 years. Clinically satisfactory results were 27% at 16.2 years
      compared with 78% at 4.5 years and 58% at 9.2 years. The revision rate increased
      from 12% at 4.5 years to 33% at 9.2 years to 67% in this study. The revision rate
      for patients younger than 30 at the time of the index arthroplasty was 82%
      compared with 56% for those over 30. Impending failure was present in 81% of the
      16 unrevised hips compared with 56% at 9.2 years and 29% at 4.5 years. Patients
      younger than 30, in Charnley category A or B, and with a diagnosis of
      osteonecrosis or osteoarthritis had the poorest clinical results. As in the
      previous two studies, the best results were obtained in category C patients who
      were over 30 years of age with inflammatory collagen disease. The purpose of this
      study is to report the long-term (average, 16.2 years) follow-up results of
      patients under the age of 45 who underwent cemented total hip arthroplasty at
      Rancho Los Amigos Medical Center between 1972 and 1978. The 4.5-year and 9.2-year
      results form the basis for comparison.

PMID- 7807102
TI  - Primary total hip arthroplasty using noncemented porous-coated femoral components
      in patients with osteonecrosis of the femoral head.
AB  - Ninety consecutive total hip arthroplasties in 73 patients with osteonecrosis of
      the femoral head yielded 81 hips in 64 patients (37 men and 27 women) available
      for evaluation after a 4-8-year follow-up period. The average age at surgery was
      39.9 years (range, 20-66 years). Osteonecrosis etiology was idiopathic in 13
      hips, alcohol-induced in 15, femoral neck fracture in 12, and slipped capital
      femoral epiphysis in 2. The remaining 39 cases were related to steroids, which
      were administered for a variety of reasons. Two types of noncemented, porous
      coated, straight-stem femoral components and three types of acetabular components
      were utilized. Good or excellent clinical results were recorded in 80.2% of the
      patients. Average Harris hip scores improved from 52.9 to 87.9 points. Nine
      patients required revision of at least one component and were significantly
      younger than those with unrevised components. A revision rate of 24.1% was
      recorded in patients under 35 years of age at the time of primary surgery. Good
      or excellent clinical results were seen in 92.3% of the idiopathic cases, 86.7%
      of the alcohol-induced cases, 77.8% of the renal transplant cases, and 62.5% of
      the systemic lupus erythematosus cases. The overall mortality rate at the follow
      up evaluation was 14%; it was 50% in renal transplant patients. Analysis of the
      clinical results based on the implants showed no significant differences in
      Harris hip scores or pain and function scores. While total hip arthroplasty using
      noncemented porous-coated femoral stems appears to give better results than
      cemented procedures in patients with osteonecrosis of the femoral head, the
      results appear to be inferior to those reported in patients with other diagnoses.

PMID- 7807103
TI  - Midterm results (5.5-10 years) of acetabular allograft reconstruction with the
      acetabular reinforcement ring during total hip revision.
AB  - Acetabular reconstructions using frozen femoral head allografts and the
      acetabular reinforcement ring of M. E. Mueller (Protek AG, Bern) have been
      analyzed after an average follow-up period of 7.2 years (range, 5.5-10 years) in
      27 patients/hips. The deficiencies, according to the American Academy of
      Orthopaedic Surgeons classification, were 1 segmental, 14 cavitary, and 12
      combined cavity and segmental. Twenty-two (82%) of the reconstructions were
      classified as adequate and five (18%) as inadequate based on the operative report
      and radiographic assessment, including anteroposterior, oblique, and lateral
      views. Reconstructions were considered adequate if an appropriate sized ring had
      been used in accordance with the recommendations of the authors (contact on host
      pelvic bone cranially, posteriorly, and inferomedially). Radiographic evaluation
      revealed acetabular component migration of more than 2 mm in 12 reconstructions
      (44%). Of these, cranial migration averaged 4 mm (range, 2-9 mm) in inadequate
      reconstructions, whereas it averaged only 2 mm (range, 1-4 mm) in adequate
      reconstructions. The incidence of migration in adequate reconstructions for
      segmental only and combined cavitary and segmental defects was 6 of 12 (50%),
      whereas it was 1 of 10 in reconstructions of cavitary deficiencies. Kaplan-Meier
      survivorship analysis revealed a 79.6% probability of survival at 10 years with
      revision as the endpoint for failure. It is concluded that durability of the
      reconstruction can be expected if support of the metallic reinforcement device is
      provided by host-bone. Segmental and combined deficiencies may require additional
      internal fixation by plates and screws.

PMID- 7807104
TI  - Costs of elective total hip arthroplasty during the first year. Cemented versus
      noncemented.
AB  - The cost-effectiveness of the Mallory Head (Biomet, Warsaw, IN) cemented versus
      noncemented total hip arthroplasty was determined as part of a randomized trial.
      Costs were assessed during the first postoperative year. In-hospital resource use
      was determined using a chart review of 60 randomly selected patients. Costs were
      determined using a fully allocated costing model. Outpatient resource use was
      determined using patient diaries, and appropriate costs were allocated for
      outpatient visits, admissions to hospital, and patient-borne costs. There was no
      difference in costs between the cemented and noncemented prostheses. The average
      cost of the initial hospitalization was $9,990 (1988 Canadian dollars), and
      outpatient costs during the first year were $1,137 (total cost during the first
      year was $11,127). The cost per quality adjusted life year was $27,139 during the
      first year and $8,031 during the first 3 years.

PMID- 7807105
TI  - Taperloc femoral component. A 2-6-year study of the first 100 consecutive cases.
AB  - The first 100 consecutive patients who underwent insertion of the Taperloc
      (Biomet, Warsaw, IN) femoral stem were prospectively studied with a mean follow
      up period of 3.8 years (range, 2-6 years). Two of the original 100 patients were
      lost, giving a 98% follow-up rate. The diagnoses included osteoarthritis (76
      patients), avascular necrosis (19), rheumatoid arthritis (3), chrondrolysis (1),
      and post-traumatic arthritis (1). The mean age at surgery was 56 years (range, 25
      79 years), mean weight was 78 kg (range, 45-127 kg), and the female to male ratio
      was 29:71. Charnley pain and function scores were 3.0 and 2.8 before surgery and
      5.5 and 5.4 after surgery. Thigh pain was present in 2% of the patients at the
      final follow-up evaluation. There were no revisions. Radiographic signs of bone
      ingrowth fixation (calcar atrophy, spot welds) were seen in 92 of 94 components
      (98%). No component had complete demarcation of the porous-coated zones. Fifty
      two of 94 patients were able to be matched for age, sex, weight, diagnosis, and
      length of follow-up period with a series of patients who received a contemporary
      cemented total hip. In this matched subset, the Charnley pain and function scores
      were 5.6 and 5.5 for the cementless Taperloc stem and 5.7 and 5.5 for the
      cemented control group; this is not a significant difference. These data indicate
      a clinical performance equivalent to a matched group of contemporary cemented
      total hip arthroplasties.

PMID- 7807106
TI  - Primary total knee arthroplasty in the elderly.
AB  - In a retrospective study, the authors investigated the outcome of primary total
      knee arthroplasty in patients aged 75 years or older. There is an increased risk
      of perioperative mortality and medical morbidity, but not surgical morbidity. The
      results were equal to the younger control group in terms of patient satisfaction,
      pain relief, stability, range of motion, residual degree of flexion contracture,
      and extension lag. Mobility was less impressive in the elderly group; factors
      included were ability to walk, use of walking aids, gait, ability to get out of a
      chair, and ability to climb stairs.

PMID- 7807107
TI  - Natural history of uncorrected flexion contractures following total knee
      arthroplasty.
AB  - Over a 2-year period, 29 patients were identified that had preoperative flexion
      contractures less than 30 degrees and were not fully corrected to neutral
      following total knee arthroplasty. They were followed after surgery at 3, 6, and
      12 months, and yearly thereafter with complete clinical and roentgenographic
      examinations to determine the natural history of the flexion contracture and its
      effect on the clinical outcome. The mean age of the 10 women and 19 men was 66
      years (range, 47-80 years). The mean preoperative flexion contracture was 11
      degrees (range, 5 degrees-30 degrees). The mean follow-up period was 33 months
      (range, 24-60 months). The mean values of the flexion contractures at each follow
      up period were; immediately after surgery, 10.5 degrees; at 3 months, 5 degrees;
      at 6 months, 2 degrees; at 12 months, 1 degree; and at 24 months, 1 degree (P <
      .0001). Resolution of the flexion contracture did not vary between patients under
      and over the age of 65 years. There was no statistically significant difference
      in the residual flexion contracture when knees with preoperative contractures
      from 0 degrees to 14 degrees and 15 degrees to 30 degrees were compared. The
      clinical outcome was not affected by the residual flexion contracture after 6
      months of follow-up evaluations. Significant improvements can occur after surgery
      with rehabilitation, and it appears that complete intraoperative correction is
      not necessary. There appears to be no difference in the natural history of
      flexion contractures with regard to age or severity up to 30 degrees.

PMID- 7807108
TI  - High hip center in revision arthroplasty.
AB  - What is the effect of superior placement of the acetabulum in complex hip
      reconstruction? Twenty-two patients (23 cases) had revision hip arthroplasty with
      superiorly placed porous-coated components without bone-grafts. Cemented femoral
      components were used in 21 cases and ingrowth components in 2. The average
      vertical height (corrected for magnification) was 36.8 mm from the interteardrop
      line, compared to a contralateral normal height of 12.1 mm. Three patients were
      deceased. The remaining 19 patients (20 hips) had a minimum 2-year follow-up
      period (average, 35 months). Fourteen hips had two or more previous surgeries.
      Seven acetabular components had thin (< 1 mm), nonprogressive, incomplete
      radiolucent lines. One acetabulum had a complete 1 mm radiolucent line in an
      asymptomatic patient. The remaining 12 acetabular components had no evidence of
      radiolucent lines and none of the acetabular components migrated. One hip with a
      cemented femoral component had evidence of possible loosening. Two cemented
      femoral components had evidence of definite loosening, one with minimal clinical
      symptoms and the other was revised to a long stem at 14 months after revision. Of
      the two ingrown femoral components, one had initial subsidence of 1.5 cm and both
      had thigh pain. All other patients had improved from their preoperative status;
      however, 4 of 20 hips had moderate to severe pain. Superior cup position did not
      result in concomitant lateral position. With a short-term follow-up period
      however, vertical displacement alone resulted in high loosening rates, with 25%
      for the femur and 5% for the acetabulum.

PMID- 7807109
TI  - Fractures of the ipsilateral femur after hip arthroplasty. A statistical analysis
      of outcome based on 487 patients.
AB  - A complete review of the literature revealed 487 patients in 26 published reports
      with ipsilateral femur fractures occurring about the femoral prosthetic stem.
      This review included general surveys, multicenter studies, and case reports.
      Based on these studies, the authors divided the fractures into six types: type 1,
      intertrochanteric; type 2, proximal femur; type 3, spanning the prosthesis tip;
      type 4, distal to the prosthesis tip; type 5, comminuted blowout; and type 6,
      supracondylar. Type 1-5 fractures were stratified into the following treatment
      groups: traction, casting and partial weight bearing, cerclage wiring,
      screw/plate fixation, long-stem revision with plus/minus supplementation fixation
      or bone-graft, and other less frequently reported techniques. A statistical
      analysis of each type of fracture in terms of the various treatments used and the
      clinical outcome was performed. The best results based on the literature would be
      cerclage wiring or long-stem revision for types 2, 3, and 5 fractures (P < .02).
      For type 4 fractures, traction and long-stem revisions were about equally
      successful (at 77 and 74%, respectively), and were both superior to screw/plate
      fixation or cerclage fixation (P < .01). Other factors, such as cemented versus
      cementless prostheses, stable versus unstable prostheses, overall medical
      condition of the patient, and other parameters, should be analyzed and considered
      when choosing a treatment course. Based on the authors' results, suggestions for
      the treatment of each fracture type are offered.

PMID- 7807110
TI  - Management of ipsilateral supracondylar femur fractures following total knee
      arthroplasty.
AB  - A complete review of the literature revealed 195 fractures in 12 published
      studies of ipsilateral supracondylar femur fractures occurring about a total knee
      arthroplasty. This review included general surveys, multicenter studies, and case
      reports. Based on these studies, the authors divided the fractures into
      nonoperative and operative treatment groups. The fracture types were also
      subclassified into nondisplaced (Neer type 1) and displaced (Neer types 2 and 3).
      Statistical analysis of each type of fracture in terms of the various treatments
      and clinical outcome was performed. This study revealed satisfactory results in
      83% of the patients with nondisplaced fractures that were treated without
      surgery. In contrast, 64% of all patients with displaced fractures that were
      treated with or without surgery had satisfactory outcomes. This difference is
      statistically significant (P < .05). Of the patients with displaced fractures,
      nonoperative versus operative results were not statistically significant (P < .9)
      (67% satisfactory vs 61%). A treatment algorithm is proposed based on the above
      data.

PMID- 7807111
TI  - A clinical and radiographic study of the "safe area" using the direct lateral
      approach for total hip arthroplasty.
AB  - The purpose of this clinical and radiographic study is to determine whether the
      surgeon can remain within the 5 cm "safe zone" while using the direct lateral
      approach during total hip arthroplasty (THA) without endangering the superior
      gluteal nerve. The direct lateral approach was used in a prospective, consecutive
      series of 36 primary THAs in 31 patients performed by one surgeon. At the time of
      closure of the abductor muscle layer, a small metallic clip was placed at the
      superior extent of the incision into the gluteus medius. After surgery, the
      patients were mobilized on crutches with protected weight bearing for either a 6
      week (hybrid THA) or 12-week (uncemented THA) period. Before surgery, and at 3,
      6, and 12 months after surgery, abductor strength and the Trendelenburg sign were
      measured by the same physical therapist. The vertical distance from the superior
      pole of the greater trochanter to the base of the clip was measured on all
      radiographs of the pelvis and corrected for magnification. Before surgery, only
      25 of the 36 hips demonstrated abduction strength of 4/5 or greater. Three months
      after surgery, 34 hips had a grade of 4/5 or greater for abductor strength. The
      Trendelenburg sign was positive in 24 of 34 hips before surgery, in 5 hips at 3
      months, in 1 hip at 6 months, but negative in all hips by 12 months. The clip was
      located 3.2 +/- 1.3 cm (mean +/- SD) vertically from the superior pole of the
      greater trochanter. In 34 of 36 hips (95%), the 5 cm safe zone was
      respected.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7807112
TI  - Measurement of polyethylene thickness in total hip arthroplasty. A technique
      analysis.
AB  - Accurate radiographic measurement techniques are necessary to evaluate wear
      characteristics of different metals, ceramics, and plastics. This study evaluated
      a standard technique for radiographic measurement of acetabular component
      thickness. Twenty-one acetabular components retrieved after revision surgery were
      studied. Radiographic measurement of polyethylene thickness was performed at two
      points on radiographs taken within 2 months of the revision surgery. Measurements
      were made at the area of greatest polyethylene wear and at the center of the
      component, and these measurements were compared to direct measurement of the
      retrieved component. The 42 data points obtained revealed an average difference
      between the radiographic and direct measurements of 0.18 mm. A regression model
      demonstrated no significant difference (P = .85) between these measurements.
      Additionally, when comparing the central-point measurement to the thinnest wear
      point measurement, no difference was noted, indicating that wear in the sagittal
      plane did not affect radiographic measurement accuracy. Radiographic measurement
      of acetabular component thickness is accurate to within 0.18 mm. This degree of
      accuracy allows for radiographic wear analysis, as long as the standard
      measurement technique is utilized.

PMID- 7807113
TI  - Revision total knee arthroplasty. Comparison of outcome following primary
      proximal tibial osteotomy or unicompartmental arthroplasty.
AB  - Forty-three patients who had undergone revision total knee arthroplasty following
      either primary, medial unicondylar arthroplasty (23 patients) or valgus tibial
      osteotomy (20 patients) for medial compartment osteoarthritis were reviewed.
      Although the two groups had similar knee scores and range of motion at review,
      six patients (30%) who had undergone prior tibial osteotomy suffered serious
      postoperative complications. Of these, four patients had a deep infection. It was
      felt that several factors were responsible, resulting largely from difficulties
      in gaining access to the lateral tibial plateau and subsequently causing
      impairment of wound vascularity and healing. In contrast, those patients
      undergoing revision of unicondylar prostheses did not experience wound healing
      problems, but it was noted that in half of the cases, there was significant bone
      loss from the medial tibial plateau.

PMID- 7807114
TI  - Color duplex Doppler ultrasound scanning for detection of deep venous thrombosis
      in total knee and hip arthroplasty patients. Incidence, location, and diagnostic
      accuracy compared with ascending venography.
AB  - Ninety-nine patients undergoing total hip arthroplasty (THA) or total knee
      arthroplasty (TKA) were prospectively studied for deep venous thrombosis (DVT) of
      the lower extremity. Eighty-three hips in 42 THA patients and 107 knees in 57 TKA
      patients were studied with noninvasive color duplex Doppler ultrasound flow
      scanning and ascending venography 3-9 days after surgery. In all patients,
      surveillance studies were performed within 24 hours. The ultrasonographer and
      radiologist were blinded to the study. The incidence of DVT was significantly
      greater following TKA (61%) than THA (17%) (P < .001). After TKA, significantly
      more DVT was found in the ipsilateral (32 of 57 patients) versus contralateral
      knees (3 of 50 patients), and more thrombi were located below the knee (34 of 107
      knees) than above the knee (1 of 107 knees) (P < .001). More thrombi were found
      in the contralateral limb after THA (5 of 41 patients vs 3 of 42 patients), but
      this was not significant. Two patients developed nonfatal pulmonary emboli. The
      sensitivity of color flow scanning was relatively poor initially (67% of above
      knee patients and 57% of below-knee patients), but improved in the last 50
      patients (100% of above-knee patients and 79% of below-knee patients). Negative
      predictive values exceeded 90% in the THA group and 87% in the TKA group.
      Positive predictive values ranged from 89 to 100%. Specificity was always above
      96%. Longitudinal ultrasound scanning with the newer Quantum 2000 angiodynograph
      (Issaquah, WA) provided the best image quality.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7807115
TI  - Reliability and validity of the grading of heterotopic ossification.
AB  - The purpose of this study is to assess the reliability and validity of the
      Brooker grading of heterotopic ossification. Anteroposterior hip radiographs of
      77 patients, taken 6 months following total hip arthroplasty, were blindly
      evaluated twice by two surgeons using the Brooker scale. Patients were also
      evaluated with the Harris hip scale, and range of motion of the hip was
      determined. All inconsistencies in heterotopic ossification grading were reviewed
      by the same two surgeons who developed six points of clarification to minimize
      ambiguities in the Brooker grading criteria. A second set of 76 radiographs were
      reviewed by the two surgeons using this modified Brooker index. The intraobserver
      reliability of the two readers was good, with agreements of 77 and 86% and
      weighted kappa values of 0.63 and 0.69, respectively. The two surgeons
      demonstrated fair interobserver reliability on the first reading (agreement of
      68% and weighted kappa of 0.57) that improved to a good level of reliability
      (agreement of 77% and weighted kappa of 0.68) using the revised Brooker index.
      The grade of heterotopic ossification was correlated (r = -.25, P = .005) with
      the aggregate range of hip motion, but had no relationship to the patient's
      Harris rating. In conclusion, the grading of heterotopic ossification is
      reliable. Although the severity of heterotopic ossification did not correlate
      with the Harris scale, the relationship between heterotopic ossification and
      range of motion indicates that the Brooker index is also a valid measurement.

PMID- 7807116
TI  - Osteolysis associated with cemented total knee arthroplasty. A case report.
AB  - Osteolysis induced by particulate debris occurs within 5 years after cementless
      total knee arthroplasty, but has not been reported to be a problem after cemented
      total knee arthroplasty. It has been suggested that the bone-cement interface may
      form a barrier to polyethylene-debris migration, thereby limiting bone loss. The
      authors have observed osteolysis in a 75-year-old woman 9 years after cemented
      total knee arthroplasty. An osteolytic area appeared to return to an area of
      normal bone architecture 3 years after the removal of synovium and particulate
      debris without implant revision.

PMID- 7807117
TI  - Fatal massive adrenal hemorrhage after bilateral total knee arthroplasty.
AB  - Adrenal hemorrhage can occur in association with postoperative stress, trauma,
      myocardial infarction, infection, and chronic medical illness. Other risk factors
      for the development of spontaneous adrenal hemorrhage include a thromboembolic
      state and anticoagulation therapy, although it has rarely been observed following
      orthopedic surgery. The authors report the case of an otherwise healthy 61-year
      old woman who died suddenly 9 days after bilateral total knee arthroplasty. The
      only abnormality found on postmortem examination was massive bilateral adrenal
      hemorrhage with destruction of nearly all adrenal tissue. Surgeons should be
      aware of this complication that, if recognized early, can be treated with steroid
      replacement.

PMID- 7807118
TI  - Dislocation following posterior-stabilized TKA.

PMID- 7807119
TI  - Khusimol, a non-peptide ligand for vasopressin V1a receptors.
AB  - In the course of a random screen of various plant extracts, khusimol [1], a non
      peptide molecule isolated from the root of Vetiveria zizanioides, was found to
      competitively inhibit the binding of vasopressin to rat liver V1a receptors (Ki =
      50 microM). The 1H- and 13C-nmr spectra of this sesquiterpene alcohol were
      assigned unambiguously.

PMID- 7807120
TI  - Bistramides A, B, C, D, and K: a new class of bioactive cyclic polyethers from
      Lissoclinum bistratum.
AB  - The isolation and characterization is described of four novel cyclic polyethers,
      bistramides B [2], C [3], D [4], and K [5], which are closely related to the
      previously reported bistramide A [1] from the New Caledonian urochordata
      Lissoclinum bistratum. The structures of these metabolites were defined by
      spectroscopic methods. The four compounds exhibited in vitro cytotoxicity toward
      six tumor cell lines, including the human non-small cell lung carcinoma (NSCLC
      N6) line. Cytofluorimetric analysis with bistramide K showed a complete block of
      NSCLC-N6 cells in the G1 phase. Bistramide D and particularly bistramide K are
      less toxic than bistramides A, B, and C and are thereby effective in vivo against
      NSCLC-N6.

PMID- 7807121
TI  - Cytotoxic saponins from New Zealand Myrsine species.
AB  - The observed biological activity in two New Zealand Myrsine species has been
      shown to be due to the presence of triterpene saponins. From Myrsine australis a
      series of eight oleanane-type saponins was obtained, with compounds 1-4 and 7 and
      8 being novel. Also isolated were ardisiacrispin A [5] and ardisiacrispin B [6].
      The structures of the new compounds were determined by chemical and spectroscopic
      techniques. Extracts of Myrsine salicina yielded only one saponin, 5. Saponins 1
      8 were shown to be combinations of four oleanane triterpenes bonded to beta-D
      xylp(1-->2)-beta-D-glcp(1-->4)-[beta-D-glcp(1-->2)]-alpha-L -arap (compounds 1,
      3, 5, 7) and this same tetrasaccharide with alpha-L-rhap replacing the beta-D
      xylp unit (compounds 2, 4, 6, 8).

PMID- 7807122
TI  - New cytotoxic peroxylactones from the marine sponge, Plakinastrella onkodes.
AB  - Three new peroxylactones, plakortolides B [6], C [7], and D [8], and a new peroxy
      ester, epiplakinic acid E methyl ester [9], were isolated and characterized from
      a previously unstudied marine sponge, Plakinastrella onkodes. A mixture of
      steroidal peroxides was also found in this organism. Plakortolides B [6] and D
      [8], and epiplakinic acid E methyl ester [9], were evaluated for biological
      activity and found to show cytotoxicity against the A549 human lung carcinoma and
      P388 murine leukemia cell lines, and to effect adhesion in an assay employing the
      EL-4.IL-2 cell line, which correlates with signal transduction activity.

PMID- 7807124
TI  - Profiling taxanes in Taxus extracts using lc/ms and lc/ms/ms techniques.
AB  - Analytical methodology developed for the trace analysis of natural products in
      crude extracts was utilized for the rapid and systematic structure elucidation of
      taxanes in Taxus extracts and process intermediates. This method integrates
      analytical hplc, uv detection, uv spectroscopy, full-scan ionspray mass
      spectrometry and tandem mass spectrometry on-line. The identification of
      structure of a taxane is based on comparing the mass spectrometric
      characteristics of the taxane with the paclitaxel substructural "template."
      Analytical data for taxanes in preparations from Taxus brevifolia and Taxus
      baccata were observed, including chromatographic characteristics using a standard
      hplc system, molecular weight, and collision induced dissociation (cid) tandem
      mass spectrometry (ms/ms) product ion spectra. The data obtained for 18 taxanes
      from natural sources using this method provided a taxane profile database useful
      for the rapid identification of taxanes in mixtures and samples of limited
      quantity.

PMID- 7807123
TI  - Five new labdane diterpenes from Amphiachyris amoena.
AB  - Five new labdane diterpenes, amoenolide A 19-aldehyde [2], and amoenolides B [3],
      C [4], D [5], and J [6] were isolated from the above-ground parts of Amphiachyris
      amoena, and their structures determined by spectral methods, in particular high
      field nmr, and selective chemical studies. Amoenolide J [6] had its carbon
      skeleton established by the INADEQUATE 13C-13C connectivity nmr experiment.

PMID- 7807125
TI  - Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry of
      paclitaxel and related taxanes.
AB  - Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry has
      been demonstrated for the analysis of Taxus brevifolia extracts. The detection
      limit for the taxanes contained therein is estimated at 1 pmol using the matrix 4
      nitroaniline at a matrix-to-analyte molar ratio of 100:1. Acquisition and
      calibration of the mass spectral data requires less than 5 min. The [M+H]+,
      [M+Na]+, and [M+K]+ ions provide mol wt confirmation and structurally significant
      fragment ions indicative of the various substituent groups located on the
      diterpene skeleton are formed.

PMID- 7807126
TI  - Ellagitannins and complex tannins from Quercus petraea bark.
AB  - The ellagitannins 2,3-(S)-hexahydroxydiphenoyl-glucose, pedunculagin, vescalagin,
      and castalagin; the flavanoellagitannins acutissimin A, acutissimin B,
      eugenigrandin A, guajavin B, and stenophyllanin C; and the
      procyanidinoellagitannin mongolicanin have been isolated from the bark of Quercus
      petraea. The ellagitannin fraction had a weak antisecretory effect.

PMID- 7807127
TI  - Hamacanthins A and B, new antifungal bis indole alkaloids from the deep-water
      marine sponge, Hamacantha sp.
AB  - Hamacanthin A [1] and hamacanthin B [2] are two bioactive
      dihydropyrazinonediylbis(indole) alkaloids isolated from a new species of deep
      water marine sponge, Hamacantha sp. The hamacanthins are growth inhibitors of
      Candida albicans and Cryptococcus neoformans. Isolation and structure elucidation
      of 1 and 2 by nmr spectroscopy are described.

PMID- 7807128
TI  - Cucurbitacins: differential cytotoxicity, dereplication and first isolation from
      Gonystylus keithii.
AB  - A characteristic pattern of differential cytotoxicity of extracts of Iberis amara
      seeds, predominantly toward renal tumor, brain tumor, and melanoma cell lines in
      the NCI human disease-oriented tumor screening panel, was traced to cucurbitacins
      E [1] and I [2]. This same differential cytotoxicity profile was detected in
      extracts of Begonia plebeja and Gonystylus keithii. Computer-assisted recognition
      of these profiles was followed by a rapid chemical fractionation, thus permitting
      the efficient dereplication of those extracts containing cucurbitacins B [3] and
      D [4], respectively. This is the first report of cucurbitacins from the genus
      Gonystylus.

PMID- 7807129
TI  - Stellettin A, a new triterpenoid pigment from the marine sponge Stelletta tenuis.
AB  - A new isomalabaricane triterpenoid, stellettin A [1], was isolated from the
      sponge Stelletta tenuis collected off Hainan Island, People's Republic of China.
      Its structure and stereochemistry were established by analysis of its spectral
      data and reference to related compounds.

PMID- 7807130
TI  - Zarzissine, a new cytotoxic guanidine alkaloid from the Mediterranean sponge
      Anchinoe paupertas.
AB  - From a CH2Cl2 extract of the Mediterranean sponge Anchinoe paupertas were
      isolated and characterized zarzissine [2], a new 4,5-guanidino-pyridazine
      compound and the known p-hydroxybenzaldehyde [1]. The structure of zarzissine [2]
      was elucidated by spectroscopic methods, including the application of a number of
      2D nmr techniques. Biological activities of compounds 1 and 2 were also
      determined, with zarzissine exhibiting cytotoxicity against three human and
      murine tumor cell lines.

PMID- 7807131
TI  - Identification of an activator of the retinoid X receptor.
AB  - A metabolite of all-trans retinoic acid produced by insect cells was discovered
      to activate the intracellular retinoic acid X receptor. The compound, beta
      glucopyranosyl 9-cis-retinoate [1], was purified and its structure was determined
      by analysis of spectroscopic data.

PMID- 7807132
TI  - Corticatic acids A-C, antifungal acetylenic acids from the marine sponge,
      Petrosia corticata.
AB  - Three new acetylenic acids, corticatic acids A-C [1-3] have been isolated from
      the marine sponge, Petrosia corticata. Their structures were determined by
      spectroscopic methods, and 1-3 exhibited antifungal activity against Mortieralla
      ramanniana.

PMID- 7807133
TI  - Papers from the 3rd International Symposium on Amyotrophic Lateral
      Sclerosis/Motor Neurone Disease. Genetics and Cell Biology of the Motor Neurone.
      Birmingham, United Kingdom, November 2-4, 1992.

PMID- 7807135
TI  - Classification of neuromuscular disorders.

PMID- 7807134
TI  - Research, care and the associations: an era for partnership.

PMID- 7807136
TI  - Evidence for autoimmunity in amyotrophic lateral sclerosis.
AB  - Although the etiology and pathogenesis of ALS is unknown, increasing evidence
      supports a role for autoimmune mechanisms in motoneuron degeneration and death.
      An animal model, experimental autoimmune gray matter disease, can be induced by
      the inoculation of spinal cord gray matter. The experimental disease is
      characterized by weakness secondary to the loss of upper and lower motoneurons,
      accompanied by inflammatory foci within the spinal cord, and IgG at the
      neuromuscular junction and within UMN and LMN. In human ALS, IgG is present
      within the UMN and LMN, and T-lymphocytes and activated microglia have been
      identified within spinal cord gray matter and motor cortex. ALS IgG can passively
      transfer physiological changes of the neuromuscular junction to mice resulting in
      enhanced release of acetylcholine. The ALS IgG selectively interact with calcium
      channels and alter channel function. These data suggest a potential role for
      autoimmune mechanisms in the destruction and loss of motoneurons in ALS.

PMID- 7807137
TI  - Aluminum neurotoxicity: an experimental approach to the induction of
      neurofilamentous inclusions.
AB  - Acute or chronic aluminum neurotoxicity experiments in the rabbit suggest that
      aluminum can induce phosphorylation of neurofilamentous proteins. This may result
      in abnormal resistance to degradation or transport of neurofilament protein and
      so to the accumulation of neurofilaments in abnormal cells. The possible
      importance of this process in ALS is considered in relation to the
      neurofilamentous abnormalities characteristic of intraneuronal inclusions in ALS
      and in other neurodegenerative disorders.

PMID- 7807138
TI  - The role of intracellular free calcium in motor neuron disease.
AB  - The intracellular calcium (Ca2+) concentrations of motoneurons can be altered by
      the influx of Ca2+ into the cell by the opening of voltage-dependent Ca2+
      channels and ligand-gated channels linked to Ca2+ influx, especially by the N
      methyl-D-aspartate (NMDA) type of excitatory amino acid receptor. Intracellular
      Ca2+ concentration is also affected by the release of Ca2+ buffered in
      mitochondria and endoplasmic reticulum. Evidence that motoneurons may be
      selectively vulnerable to Ca(2+)-induced cell death include the following
      observations: (i) the presence of excitatory amino acid receptors on the cell
      membranes of motoneurons, some of which would permit Ca2+ influx (e.g. NMDA
      receptors); (ii) the availability of the presynaptic terminal for antibody
      mediated effects leading to changes in cell permeability and Ca2+ influx; and
      (iii) the limited amounts of intracellular Ca(2+)-binding proteins such as
      calbindin D28K and parvalbumin in motoneurons. Elevation of intracellular free
      Ca2+ may also be a common event in a number of independent mechanisms leading to
      motoneuron death in motor neuron disease.

PMID- 7807139
TI  - Cytoskeletons of central and peripheral neurons.
AB  - All eukaryotic cells have a cytoskeleton, consisting of microtubules,
      intermediate filaments and microfilaments. The cytoskeletal structure of cells
      and cell processes in the central nervous system is diverse. The generation of
      animal models in which specific mutations result in underexpression of
      overexpression of particular intermediate filament and microtubular proteins
      allows assessment of the possible role of cytoskeletal abnormalities in the
      neurodegenerative disorders. It is suggested that overexpression of filaments is
      likely to be the more significant process, but that neurofibrillary change, as
      recognized by the neuropathologist represents the final result of failure of any
      of a large number of molecular processes involved in cytoskeletal protein
      turnover.

PMID- 7807140
TI  - New pathological findings in amyotrophic lateral sclerosis.
AB  - There have been recent developments in the pathology of sporadic ALS. A new
      filamentous neuronal inclusion body in ALS detected by immunohistochemical
      localisation of the protein ubiquitin has been characterised at the light
      microscopic and ultrastructural level and appears specific for the disease. The
      molecular composition of underlying filaments remains unresolved but the quest
      for this is a major aim in ALS research. Despite being a progressive degenerative
      process which primarily affects motor systems, ALS is now recognised to involve
      several non-motor systems and in long survivors affects many subcortical
      structures. There is also accumulating evidence that the neurodegenerative
      process underlying ALS may present as a non-motor clinical syndrome, particularly
      as a frontal lobe dementia with characteristic inclusions present in the non
      motor cortex. Considering ALS as a multisystem disease rather than simply a
      disease of motor neurones has major implications for research into pathogenesis.

PMID- 7807141
TI  - Excitotoxicity and cholinergic chemical markers during programmed motor neurone
      death.
AB  - We measured cholinergic markers and acetylcholinesterase (AChE) molecular forms
      after glutamate receptor stimulation of superfused slices of mouse spinal cord at
      different developmental ages. AChE globular forms were secreted in a dose
      dependent fashion. A period of selective sensitivity to excitotoxic agents was
      detected by increased acetylcholine (ACh) release and AChE secretion (sAChE) at
      postnatal day 14. Strychnine-resistant glycine stimulation potentiated glutamate
      induced AChE release, suggesting N-methyl-D-aspartate (NMDA) receptor
      involvement.

PMID- 7807142
TI  - POMC neuropeptides and their receptors in the neuromuscular system of wobbler
      mice.
AB  - The pro-opiomelanocortin-derived peptides, beta-endorphin (beta-EP), ACTH and
      alpha-MSH act in concert to promote synaptogenesis and nerve growth in the
      neuromuscular system. Immunocytochemistry was used to detect the peptides in
      triceps muscles of normal developing and adult mice and in adult wobbler mice
      with motor neurone disease. Immunoreactivity for beta-EP and alpha-MSH/ACTH was
      present in some intramuscular motor nerves. There was a significantly higher
      proportion of immunoreactive nerves in the muscles of the developing and the
      diseased mice than in the normal adults. ACTH and beta-EP receptors were revealed
      using autoradiography. Specific binding sites for 125I-labelled ACTH and 125I
      labelled beta-EP were present in some fibres in all muscles examined. There were
      significantly higher proportions of fibres exhibiting specific beta-EP and
      specific ACTH binding sites in the muscles of the developing and the diseased
      mice compared to the muscles of normal adults. It seems likely that the high
      incidence of immunoreactive nerves and of muscle fibres with the peptide
      receptors in the developing and diseased mice reflects the trophic actions of the
      peptides in the neuromuscular system.

PMID- 7807143
TI  - Pathways of cysteine metabolism in MND/ALS.
AB  - Analysis of plasma from MND/ALS patients has shown no significant differences in
      metabolism of cysteine derivatives, although a sub-set of the population has
      raised glutamate values. Cysteine dioxygenase was found to have reduced activity
      in vitro, consistent with previous findings of a high plasma cysteine/sulphate
      ratio.

PMID- 7807144
TI  - Excitotoxicity and motor neurone disease: a review of the evidence.
AB  - Excitotoxic mechanisms have a well established role in the pathogenesis of
      neuronal injury following acute CNS insults such as ischaemia and trauma. Their
      role in the selective cell death which occurs in chronic neurodegenerative
      disorders such as motor neurone disease (MND) is more speculative. The
      traditional classification of glutamate receptor subtypes which mediate
      excitotoxicity requires modification in the light of new molecular data. There is
      much greater structural and functional diversity in this receptor family than
      previously envisaged and it is quite possible that specific populations of
      neurones will be characterised by a unique profile of glutamate receptor subtypes
      which may be a factor determining their selective vulnerability. The molecular
      mechanisms underlying excitotoxic neuronal injury are still being elucidated but
      it is clear that the cascade of events resulting from elevation of intracellular
      free calcium is likely to play a major role. As well as being a primary mechanism
      of neuronal injury, excitotoxicity can secondarily damage neurones whose energy
      metabolism is impaired from some primary pathological process. The 8 lines of
      evidence that primary or secondary excitotoxic mechanisms may be involved in the
      selective neuronal injury of MND are discussed. The evidence, while still
      circumstantial, is sufficient to warrant further research effort in this field,
      not least because the emergence of pharmacological agents which modify specific
      aspects of excitatory amino acid neurotransmission offer the possibility of
      therapeutic intervention in MND.

PMID- 7807145
TI  - Motor neuron disease and exposure to chemicals--aetiological suggestions from a
      case-control study.
AB  - A recent case-control study indicates that some males are genetically predisposed
      to develop motor neuron disease if they are exposed to chemicals, particularly
      solvents. Markers for such a predisposition are hereditary for a
      neurodegenerative disease and/or a thyroid disease. The reason for this
      susceptibility might be pharmacogenetic polymorphism, which causes deficient
      detoxification entailing oxidative stress and cell death.

PMID- 7807146
TI  - Accuracy, reproducibility and variability of quantitative assessments of bulbar
      and respiratory function in motor neurone disease.
AB  - The validity of quantitative tests to assess bulbar and respiratory function used
      in therapeutic trials in motor neurone disease (MND) is studied in 26 MND and 21
      age- and sex-matched control subjects. Five raters timed repeated visual and
      auditory stimuli generated by a metronome simulating bulbar tests. For all
      raters, mean error rate was 5.07%, correlation coefficient was 0.89 (and
      %difference of 1.53), and coefficient of variation (CV) was 3.18%. The
      experienced rater obtained significantly better %differences and CV. For all
      subjects and tests, mean correlation coefficient was 0.98, and mean CV was 8.8%.
      There were no significant differences in reproducibility or variability in
      readings obtained in MND and control subjects assessed by the experienced rater.
      The use of composite bulbar, but not respiratory, scores resulted in significant
      improvements in reproducibility and variability.

PMID- 7807147
TI  - Further studies on the occurrence of serum autoantibodies against a membrane
      bound AChE fraction in ALS/MND patients and controls.
AB  - Autoantibodies of the IgG and IgA types against a membrane bound AChE fraction
      were studied in the serum of ALS/MND patients, controls with neurological or
      autoimmune diseases, and normal controls. About 70% of ALS and progressive spinal
      muscle atrophy (PMA) patients had antibodies of both Ig types (titre > 1/81),
      compared to about 12% of neurologically diseased controls and about 8% of the
      other controls. A higher proportion of individuals having autoantibodies was
      found in the older age group in both patients and controls.

PMID- 7807148
TI  - Motor neurone disease associated with several immunological disorders: a case
      report.
AB  - A 44-year-old woman developed rheumatoid arthritis, pemphigus vulgaris and
      myasthenia gravis. Motor neurone disease appeared 2 years later. Hashimoto's
      thyroiditis was diagnosed after a severe stress in the autumn of 1991.

PMID- 7807149
TI  - Cortical function in progressive muscular atrophy and amyotrophic lateral
      sclerosis.

PMID- 7807150
TI  - Rapid purification of embryonic rat motoneurons: an in vitro model for studying
      MND/ALS pathogenesis.

PMID- 7807151
TI  - Clinical heterogeneity of familial motor neuron disease: report of 11 pedigrees
      from a population based study in Scotland. The Scottish Motor Neuron Disease
      Research Group.
AB  - Five percent of incident patients with MND in Scotland 1989-1990 had a family
      history of this disease. This paper assesses the demographic and clinical
      features of this group.

PMID- 7807152
TI  - Actions of CNTF and neurotrophins on degenerating motoneurons: preclinical
      studies and clinical implications.
AB  - Spinal motoneurons innervating skeletal muscle were amongst the first neurons
      shown to require the presence of their target cells to develop appropriately.
      Isolated embryonic chick and rat motoneurons have been used to identify
      neurotrophic factors and cytokines capable of supporting the survival of
      developing motoneurons. Such factors include ciliary neurotrophic factor (CNTF),
      which is present physiologically in high amounts in myelinating Schwann cells of
      peripheral nerves, and brain-derived neurotrophic factor (BDNF) which is
      synthesized in skeletal muscle and, after peripheral nerve lesion, in Schwann
      cells. These factors have been further analyzed for their physiological
      significance in maintaining motoneuron function in vivo, and for their potential
      therapeutic usefulness in degenerative motoneuron disease. Both CNTF and BDNF are
      capable of rescuing injured facial motoneurons in newborn rats. Furthermore, CNTF
      prolongs survival and improves motor function of pmn mice, an animal model for
      degenerative motoneuron disease, by preventing degeneration of motoneuron axons
      and somata. Thus treatment of human motoneuron disease with neurotrophic factors
      should be possible, provided that rational means for application of these factors
      can be established considering also the appearance of potential side effects.

PMID- 7807153
TI  - Treatment of ALS with high dose pulse cyclophosphamide.
AB  - Autoimmune abnormalities have been described in sporadically acquired amyotrophic
      lateral sclerosis (ALS), but ALS patients do not benefit from conventional
      immunosuppressive therapy. Because Multifocal Motor Neuropathy causes a syndrome
      mimicking the lower motor neuron involvement in ALS and responds to high dose
      cyclophosphamide, we tested whether ALS patients would respond to the same
      treatment. Eighteen patients with classical ALS initially received a high loading
      dose of intravenous cyclophosphamide (3 g/m2) followed by 6-monthly injections of
      750-1000 mg/m2. We monitored isometric strength, fine motor coordination and
      pulmonary function monthly for 3 months prior to the study, during the treatment
      phase, and for 6 months after treatment. Treatment subjects were matched to
      control subjects from the WALS natural history data base and compared on the
      basis of decline rate (megaslopes). Treatment did not alter the course of ALS.

PMID- 7807154
TI  - Coexistence of amyotrophic lateral sclerosis and Werdnig-Hoffmann disease within
      a family.

PMID- 7807155
TI  - Identification of flanking markers for the familial amyotrophic lateral sclerosis
      gene ALS1 on chromosome 21.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive, adult-onset,
      neurodegenerative disorder characterized by the death of large motor neurons from
      the cerebral cortex, brainstem, and spinal cord. The etiology of ALS remains
      unknown; however, approximately 10% of the cases are familial in nature. In the
      majority of these families, the mode of transmission is autosomal dominant.
      Recently, linkage of an autosomal dominant familial ALS (FALS) gene to the locus
      ALS1 on chromosome 21q was established. In addition, evidence was provided for
      genetic heterogeneity, with approximately 55% of families most likely linked to
      chromosome 21. The development of a number of highly informative simple sequence
      repeat polymorphisms in the region of linkage-21q21 through 21q22.1-has permitted
      us to confirm both the assignment of ALS1 to 21q and the genetic heterogeneity of
      FALS. In addition, we have been able to refine the mapping of ALS1, based on
      recombination events in two of the linked families. Flanking markers for the FALS
      gene are D21S213 on the centromeric side and D21S219 on the telomeric side. The
      candidate region is approximately 4 Mb and contains the genes copper/zinc
      superoxide dismutase (CuZnSOD); the fourth member of the class II cytokine
      receptor family (CRF2-4); and the interferon-alpha receptor (IFNAR).

PMID- 7807156
TI  - El Escorial World Federation of Neurology criteria for the diagnosis of
      amyotrophic lateral sclerosis. Subcommittee on Motor Neuron Diseases/Amyotrophic
      Lateral Sclerosis of the World Federation of Neurology Research Group on
      Neuromuscular Diseases and the El Escorial "Clinical limits of amyotrophic
      lateral sclerosis" workshop contributors.

PMID- 7807157
TI  - Subarachnoid hemorrhage: an update of pathogenesis, diagnosis and management.
AB  - Subarachnoid hemorrhage (SAH) remains a devastating neurological disorder, which
      most commonly develops after rupture of an intracranial aneurysm. Advances have
      occurred in the areas of epidemiology, diagnostic imaging, medical management and
      surgical intervention, related to aneurysmal SAH. Interested physicians must
      become aware of these and other advances to diagnose and manage this potentially
      lethal disorder more effectively. This review provides information about the
      pathogenesis and complications of aneurysmal SAH and an update of new and
      evolving treatment modalities to provide an in-depth overview for the clinician
      and researcher involved in this rapidly evolving field.

PMID- 7807158
TI  - Anabolic steroid treatment increases myofiber damage in mdx mouse muscular
      dystrophy.
AB  - In order to study whether myofiber size is an important determinant of the
      severity of dystrophic injury, mdx and control mice were treated with an anabolic
      steroid, nandrolone decanoate, for 3 weeks. Treatment resulted in a population of
      significantly smaller fibers in both strains, and was accompanied by an increase
      in the proportionate area or the number of foci of dystrophic injury in mdx
      soleus (slow-twitch) or tibialis anterior plus extensor digitorum longus (fast
      twitch) muscles, respectively. As well, serum creatine kinase activity was
      increased in steroid-treated mdx mice. Fiber centronucleation, an index of
      accumulated injury and repair, in steroid-treated mdx soleus was doubled compared
      to that observed in soleus muscles from untreated mdx mice. There was no change
      in the distribution of immunoreactive basic fibroblast growth factor, important
      in muscle cell proliferation, with the increased damage from treatment. However,
      presumptive muscle precursor cells (identified by immunoperoxidase histochemistry
      for neural cell adhesion molecule), appeared to be more abundant in foci of very
      recent fiber damage in muscles from steroid-treated than untreated mdx mice.
      Results show that mdx dystrophy is worsened by anabolic steroid treatment,
      possibly by altered influences on muscle use patterns and muscle precursor
      fusion, and is not accompanied by an increase in fiber size.

PMID- 7807159
TI  - Endocytotic activity of mouse skeletal muscle fibres after long-term denervation.
AB  - The endocytotic activity of skeletal muscle fibres and its relation to the
      denervated endplate region has been studied using horseradish peroxidase (HRP) as
      marker for endocytosis. In muscles denervated for a short time period (10-20
      days) HRP-uptake occurred in small segments of the muscle fibres near the centre
      of the muscle (endplate region). After long-term denervation (6-12 months)
      similar segments with high endocytotic activity were seen preferentially in more
      peripheral parts of the muscle fibres. Ultrastructural characteristics of
      segments with high endocytotic activity from long-term denervated muscle fibres
      include a proliferating transverse tubular system, HRP-containing bodies of
      different sizes with some very large vacuoles extending over several sarcomeres.
      These characteristics are similar to those described previously for HRP-uptake in
      the endplate region of short-term denervated muscle (Tagerud et al., J. Neurol.
      Sci., 75 (1986) 141) except that no recognizable endplate structures were
      observed in the present study. The results are discussed in relation to the fate
      of the denervated endplate and the receptive capacity for synapse formation in
      long-term denervated muscle.

PMID- 7807161
TI  - Late onset foot-drop muscular dystrophy with rimmed vacuoles.
AB  - We studied a family with late-onset (fifth or sixth decade) or asymptomatic
      hereditary myopathy of the anterior tibial muscle. The occurrence of the disease
      in two successive generations pointed out an autosomal dominant pattern of
      inheritance. The initial symptom was uni- or bilateral foot drop resembling
      peroneal paresis. Surprisingly many of the diagnosed patients were asymptomatic
      and considered themselves healthy whether there was any foot drop or not. The
      anterior tibial muscles were atrophic in patients with foot drop but the long toe
      extensors were usually and the short ones were always spared. Apparently the toe
      extensors could relieve the foot drop symptom. As shown by computed tomography
      there was often an early uni- or bilateral involvement of the semimembranosus
      muscle in males. The proband showed also a late involvement of the femoral biceps
      and the minor gluteal muscles. The muscles of the upper extremity were spared.
      The anterior tibial muscles had a characteristic myopathic alteration with rimmed
      vacuoles in histopathological study. This picture was most evident in latent
      cases without atrophy of the anterior tibial muscle, but with distinctly abnormal
      EMG of that muscle. Non-affected muscles showed only slight non-specific
      histopathological changes. We suggest that this disease is a new mild variety of
      autosomal dominant distal myopathy with rimmed vacuoles.

PMID- 7807160
TI  - Hereditary parkinsonism with multiple system degeneration: beneficial effect of
      anticholinergics, but not of levodopa.
AB  - Two siblings who exhibited hereditary parkinsonism with pyramidal signs and
      cerebellar ataxia are reported. Anticholinergics had a dramatic beneficial effect
      in both cases, but levodopa did not. This responsiveness, which is similar to
      that reported in patients with Joseph's disease, suggests dysfunction of an
      "indirect pathway" involving the globus pallidus and the subthalamic nucleus, in
      addition to that of the nigrostriatal system. We propose a new hereditary variant
      of early onset Parkinson's disease distinct from the levodopa sensitive forms of
      juvenile Parkinson's disease.

PMID- 7807162
TI  - Cognitive deficits in ischemic strokes: psychometric, electrophysiological and
      cranial tomographic assessment.
AB  - Global and specific cognitive functions were assessed in 57 patients with
      ischemic strokes subjected to clinical neuropsychiatric, psychometric,
      electrophysiological and cranial tomographic evaluation. Patients did
      significantly worse than normal controls in the Blessed dementia scale, Sandoz
      clinical assessment geriatric scale but not the Folstein mini-mental state
      examination. Of the specific cognitive functions, attention and psychomotor
      performance were significantly impaired in stroke patients when compared to
      normal controls. The impairment in global cognitive functions, attention and
      psychomotor performance was more evident in chronic than acute cases. Increasing
      age correlated positively to the deterioration in psychomotor performance and
      perception. Cranial tomographic size of infarction was significantly related to
      global cognitive as well as intentional (sensory) memory impairment. The more
      marked the conventional electroencephalographic abnormalities, the more impaired
      were the global cognitive functions. High limit of the theta percent power
      correlated positively to deterioration in psychomotor performance. All P300
      parameters except amplitude correlated significantly with impairment of global
      cognitive function and psychomotor performance in stroke patients.

PMID- 7807163
TI  - High cerebrospinal fluid and serum levels of tumor necrosis factor-alpha in
      asymptomatic HIV-1 seropositive individuals. Correlation with interleukin-2 and
      soluble IL-2 receptor.
AB  - The relationship between tumour necrosis factor-alpha (TNF-alpha) and the
      interleukin-2 (ILL-2) system in HIV-1 infection is important in understanding the
      dynamics of early immune response before the development of acquired
      immunodeficiency syndrome. Levels of TNF-alpha, IL-2 and soluble IL-2 receptor
      (sIL-2R) in serum and cerebrospinal fluid (CSF) samples from 31 asymptomatic HIV
      1 seropositive individuals were measured. High levels of TNF-alpha were detected
      in CSF of 17 (55%) and serum of 22 (71%) subjects, 15 (88%) of whom had elevated
      CSF IL-2 levels and 16 (94%) had high sIL-2R levels. Moreover, CSF levels of TNF
      alpha significantly correlated with CSF levels of IL-2 and sIL-2R. TNF-alpha, IL
      2 and sIL-2R seem to be released within the intrathecal compartment early in the
      course of HIV-1 infection. In view of the known cytotoxic effects of TNF-alpha,
      an early release may contribute to subsequent development of neurological
      complications.

PMID- 7807164
TI  - Synaptic pathology of spinal anterior horn cells in amyotrophic lateral
      sclerosis: an immunohistochemical study.
AB  - We have applied immunohistochemical techniques to study synaptic alterations of
      the spinal anterior horn in amyotrophic lateral sclerosis (ALS), and other
      disorders involving upper or lower motor neurons. A monoclonal antibody to
      synaptophysin was used. Spinal cord tissues from normal individuals served as
      controls. As compared to these, a decrease in synaptophysin immunoreactivity was
      evident in the neuropil in the spinal anterior horn of ALS patients. However,
      synaptophysin expression in the perikarya and dendrites of remaining normal
      appearing neurons in these patients was not decreased and occasionally it was
      even higher than in control neurons. Similar results were obtained with specimens
      from patients with lower motor neuron disease. Synaptophysin immunoreactivity in
      the neuropil and perikarya of the cases with focal spinal cord lesions with
      bilateral descending tract degeneration was similar to normal controls. Our data
      suggest that the alterations in synaptophysin expression occurring in ALS are
      mainly associated with the loss of lower motor neurons, and that the occasional
      increased perikaryal expression may be due to the neuronal atrophy, compensatory
      accumulation or abnormal synaptic vesicle degradation.

PMID- 7807165
TI  - Variance of sensory threshold measurements: discrimination of feigners from
      trustworthy performers.
AB  - Sensory threshold measurements are criticized as subjective and therefore not to
      be relied upon in clinical diagnostic practice, particularly when deliberate
      deception by the patient is suspected. In an attempt to devise a method which
      permits dependable sensory threshold interpretation, individual variability of
      thresholds was examined in normal and neuropathic subjects. Normals were also
      instructed to feign sensory impairment resulting from hypothetical injury. For
      each subject, a number of threshold readings were averaged, yielding individual
      means and variances. Feigning normal subjects evidenced a larger variance
      compared to trustworthy normal and neuropathic subjects. Thus, alertness to
      variance reinforces the psychophysical analysis: small variance values suggest
      trustworthy normal or pathological results, whereas large variance calls the
      interpreter's attention to feigned results or inattentive test performance.

PMID- 7807166
TI  - Expression of cytochrome c oxidase subunits encoded by mitochondrial or nuclear
      DNA in the muscle of patients with zidovudine myopathy.
AB  - The present study was carried out to determine whether a selective decrease of
      mitochondrial (mt) DNA-encoded cytochrome c oxidase (CCO) subunits occurs in
      zidovudine myopathy, as expected with a compound known to induce selective mtDNA
      depletion. Fourteen HIV-infected patients with zidovudine myopathy were studied.
      Thirteen had partial CCO deficiency assessed by histochemistry. Western blot
      analysis of CCO subunits (II/III, IV, Va, Vb, VIa, VIb, VIc, VIIa, VIIb, and
      VIIc) was performed on muscle biopsy samples. We evaluated the mtDNA-encoded
      subunits to nuclear DNA-encoded subunits ratio with the II/III to IV ratio.
      Patients had either a selective decrease of mtDNA-encoded CCO subunits (3
      patients), or an overall decrease affecting both mtDNA-and nuclear DNA-encoded
      subunits (5 patients), or a normal expression of CCO subunits (6 patients).
      Positive correlations could not be established between the pattern of expression
      of CCO subunits and total zidovudine intake, degree of inflammation, and
      percentages of ragged-red fibers or CCO-deficient fibers. The finding of a
      decrease of both mtDNA- and nuclear DNA-encoded CCO subunits suggests that a
      factor additional to zidovudine could be implicated in the pathogenesis of the
      myopathy, at least in some patients. New insights into the pathogenesis of
      zidovudine myopathy might come from the use of more sensitive methods, including
      evaluation of CCO subunits in single fibers.

PMID- 7807167
TI  - Nocturnal sleep study in multiple sclerosis: correlations with clinical and brain
      magnetic resonance imaging findings.
AB  - It has been suggested that sleep disturbances in multiple sclerosis (MS) may be
      related to periodic leg movements (PLM) during sleep, but to date
      polysomnographic studies were conducted only on small and unselected patient
      groups. Aim of this study was to evaluate 8-hour polysomnography in MS patients
      and to correlate sleep results with clinical and brain magnetic resonance imaging
      (MRI) data. Twenty-five clinically definite MS patients, without mood disorders
      and drug-free, entered the study. The patients were compared to 25 age- and sex
      matched subjects. MS patients had significantly reduced sleep efficiency and
      experienced more awakenings during sleep. No difference was found in sleep
      architecture parameters between MS patients and controls. PLM was found in 9
      patients (36%) and 2 controls (8%; p = 0.02). Of the six patients who complained
      of insomnia two had PLM and 2 others presented with PLM and central sleep apnea.
      In patients with PLM greater MRI lesion loads were detected in the infratentorial
      regions, particularly in cerebellum and brainstem. Larger studies in neurological
      diseases that produce focal lesions in these brain areas could provide useful
      information on the PLM pathogenesis.

PMID- 7807168
TI  - Diffuse noxious inhibitory control. Reappraisal by pain-related somatosensory
      evoked potentials following CO2 laser stimulation.
AB  - The effects of DNIC (diffuse noxious inhibitory control) in humans were evaluated
      by means of pain SEPs (somatosensory evoked potentials) and pain visual analogue
      scale (VAS) following CO2 laser stimulation applied to the left knee while
      conditioning stimuli (non-noxious and noxious thermal stimuli) applied to the
      right hand. Pain SEPs were recorded from scalp electrodes following laser
      stimulation applied to the left knee during various conditions as follows: (1)
      control (without any interference), (2) non-noxious (dipping the right hand in
      water at 41 degrees C for 3 min), (3) noxious (dipping the right hand in water at
      46 degrees C for 3 min), and (4) after-effect (3-6 min after taking the hand from
      the water at 46 degrees C). The present pain SEPs findings confirmed the presence
      of DNIC in humans, and indicates: (1) degree of pain relief was significantly
      correlated with changes in pain SEPs, particularly a marked decrease in
      amplitude, and a decrease in VAS; (2) DNIC was more effective on the second pain
      than the first pain; (3) the effect of DNIC gradually increased over time, but it
      rapidly disappeared after the conditioning stimuli ceased; and (4) DNIC was not
      due merely to changes of attention. I propose that the site responsible for DNIC
      is the brainstem or the spinal cord rather than the cerebral hemisphere.

PMID- 7807169
TI  - Clinically silent dysfunction of dorsal columns and dorsal spinocerebellar tracts
      in hereditary spastic paraparesis.
AB  - Hereditary spastic paraparesis (HSP) is a neurodegenerative disorder, of which
      progressive spastic paraparesis is the clinical hallmark. Given the
      neuropathological evidence of degeneration of pyramidal tracts, dorsal columns,
      and dorsal spinocerebellar tracts, it is surprising that sensory symptoms are so
      indistinct compared to motor symptoms. We investigated the involvement of
      peripheral conduction and spinal proprioceptive pathways by nerve conduction
      studies, somatosensory evoked potentials of the median and tibial nerves, and
      quantitative assessment of the vibration perception thresholds of the hands and
      feet respectively in 32 patients suffering from HSP and healthy control groups.
      We did not find peripheral conduction abnormalities in HSP patients. Log
      transformed vibration perception thresholds of the feet were abnormal in 13/32
      HSP patients and in 0/64 controls (p < 0.00001), while tibial nerve somatosensory
      evoked potentials were abnormal in 20/32 patients and in 1/17 controls (p =
      0.00001). The values for the upper extremities were within normal limits for
      nearly all subjects. In the HSP group, the neurophysiological disturbances did
      not correlate significantly with duration or severity of the disease, when age
      was controlled for, except for median nerve SSEP latency, which was affected by
      severity (p = 0.0072). We conclude that neurophysiological methods detected
      proprioceptive, subclinical abnormalities in several HSP patients, which may
      reflect degeneration of the dorsal columns, and/or dorsal spinocerebellar tracts.
      Since we found no correlation with several disease variables, the fact that not
      all HSP patients displayed these abnormalities may be caused by anatomical
      variations in proprioceptive pathways, rather than by phenotypical heterogeneity.

PMID- 7807170
TI  - Extrinsic infratentorial lesion causing ataxic hemiparesis--a new localization.
AB  - The case of an 18-year-old woman is reported who had developed progressive
      inability to use her left limbs since the age of 13 years. Ataxic hemiparesis was
      noted on the left side. A CT scan of the brain revealed a non-enhancing hypodense
      lesion in the cerebellopontine angle with a supratentorial extension consistent
      with an epidermoid. Ataxic hemiparesis has previously been reported only with
      intrinsic lesions of the brain, except for one case. An unusual clinical
      localization of this entity is reported.

PMID- 7807171
TI  - Primary central nervous system lymphoma in Japan--a retrospective, co-operative
      study by CNS-Lymphoma Study Group in Japan.
AB  - This manuscript reports the results of the first cooperative study on primary
      central nervous system lymphoma (PCNSL) in Japan. Of 196 patients registered, 170
      were judged as having PCNSL. No patients were immunocompromised. Of the 170
      patients with PCNSL, 93 were males and 77 were females. The mean was 56.7 years.
      One hundred and nineteen tumors were confirmed histopathologically, and 51 were
      diagnosed by neuroimaging alone. All the tumors were non-Hodgkin's lymphoma.
      According to the Working Formulation for Clinical Usage (WF), 96 out of 119
      tumors were classifiable: 53 were diffuse large cell type (55.2%), 17
      immunoblastic type (17.7%), 9 diffuse small cleaved type (9.4%), 6 diffuse mixed
      type (6.3%), 5 polymorphous type (5.2%), 5 small lymphocytic type (5.2%) and 1
      small non-cleaved type (1.0%). Of 21 tumors studied immunohistochemically, 18
      were B-cell type and 3 were T-cell type. Irradiated patients (144) survived
      significantly longer than non-irradiated patients, (median survival time, MST:
      19.2 and 2.7 months, respectively; p < 0.001). There was a remarkable difference
      in survival among patients of the intermediate lymphomas; MST (18 months) of
      patients with large cell lymphoma was significantly shorter than MST (over 96
      months) of patients with other intermediate grade lymphomas (small cleaved and
      mixed) (p < 0.001) and had no significant difference from MST (9 months) of
      patients with high grade lymphomas. If patients were irradiated with more than 40
      Gy, higher doses and different modes of irradiation brought no further survival
      advantage. Chemotherapy was performed in 87 of 144 irradiated patients (60.4%).
      No regimens were effective in prolonging survival. Of 144 irradiated patients, a
      complete or partial response to initial treatment was demonstrated in 91 (63.2%)
      and 43 patients (29.9%), respectively. Improvement in performance status was
      confirmed in 82 patients (57.0%). Despite a good response to initial treatments,
      88 out of 144 evaluatble patients have died of PCNSL (MST: 19 months).
      Multivariate analysis based on the Cox hazard model revealed that histology of
      tumor, age at onset, performance status, and radiotherapy were prognostic
      factors. Neither chemotherapy nor mode of surgery was a beneficial factor.

PMID- 7807172
TI  - CT and MRI features of intracranial germ cell tumors.
AB  - The computed tomographic (CT) and magnetic resonance imaging (MRI) features of 73
      histologically proven primary intracranial germ cell tumors were analysed. CT
      images were available for all 73 patients, and 22 of them were also examined by
      MRI. The tumors were classified as germinoma, mature teratoma, immature or
      malignant teratoma, yolk sac tumor, choriocarcinoma, embryonal carcinoma and
      mixed type. Germinoma was revealed as a high- or slightly high-density area on
      plain CT scan, and was enhanced homogeneously. MRI revealed iso- or slightly low
      signal intensity on T1-weighted images, and iso- or high intensity on T2-weighted
      images. Mature teratoma, which had a clear margin on neuroradiological images,
      was characterized by mixed density on CT scans, often showing large cysts and
      area of calcification. Immature or malignant teratoma had a similar pattern to
      that of mature teratoma, but the cystic components and area of calcification
      tended to be less and smaller respectively. The tumor margin was obscure in
      malignant teratoma, and perifocal edema was observed in some cases. The shape of
      yolk sac tumors was irregular. Plain CT scan revealed an iso- or low-density mass
      with good heterogeneous enhancement. Perifocal edema was observed in some cases.
      In mixed germ cell tumors, MRI imaging was useful for detecting teratomatous
      components, particularly fatty components. Although definite histological
      diagnosis cannot be achieved by CT and/or MRI alone, detailed analysis of
      neuroradiological images are useful for predicting the histological diagnosis.

PMID- 7807173
TI  - Radiation therapy combined with radiosensitizing agents for cerebral glioblastoma
      in adults.
AB  - We analyzed our treatment results of 71 operated patients with cerebral
      glioblastoma treated by conventional external radiation therapy (mean dose 60.2
      Gy) combined with radiosensitizing agents. More than 50% reduction of tumor
      volume was obtained in 20 patients (28.2%). A response rate of at least 40% was
      obtained in patients treated with combined ACNU-vincristine-nicardipine, ACNU-5FU
      hydroxyurea, or cisplatin alone. The combination of ACNU and vincristine with or
      without nicardipine resulted in significantly longer survival. The median
      survival in this group was 101.1 weeks and the two-year survival rate was 45.9%;
      these results were significantly better than those achieved with other ACNU
      combinations or other combinations without ACNU. In the analysis of survival,
      factors correlated to longer survival were a patient age of younger than 45
      years, wide resection of the tumor, a good postoperative performance status (KS >
      or = 70%), a radiation dose of 68-72 Gy, small postoperative tumor remnants (< 20
      cm3), no visible tumor after radiation therapy, and the administration of
      adjuvant chemotherapy. Maximum resection of the tumor and localized irradiation
      with a dose of 70 Gy combined with ACNU and vincristine appears to be the most
      effective treatment at present.

PMID- 7807174
TI  - Neurotoxicity and pharmacokinetics of ventriculolumbar perfusion of methyl 6-[3
      (2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU) in dogs.
AB  - Ventriculolumbar perfusion of methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6
      deoxy-alpha-D-glucopyranoside (MCNU), a water soluble nitrosourea with log P 
      0.71, may be efficacious in the treatment of subarachnoid dissemination of
      malignant glioma. We used 2 dogs to study the neurotoxicity and pharmacokinetics
      of MCNU. MCNU (1 mg), dissolved in 10 ml of artificial CSF, was administered via
      the right lateral ventricle during a period of 18 to 42 min and the CSF was
      drained by lumbar puncture. The perfusion was repeated once a week for 10
      consecutive weeks. No neurological and systemic symptoms were noted after
      perfusion. Histological examination of the brain and spinal cord showed local
      denudation of the ependyma and local subependymal spongy degeneration and gliosis
      in the lateral ventricle into which MCNU was administered in one dog and local
      denudation of the ependyma in the other. When administration was over a period of
      21 to 38 min, the MCNU concentration in the lumbar CSF peaked at 11.11 to 50.67
      micrograms/ml, in 28 to 78 min. The area under the drug concentration-time curve
      (AUC) was 1152 micrograms x min/ml on average, significantly larger than that of
      ACNU. The elimination phase followed linear kinetics and the half-time was 41.1
      min on average, significantly longer than that of ACNU. These findings suggest
      that ventriculolumbar perfusion of MCNU may be effective in the treatment of
      subarachnoid dissemination of malignant glioma notwithstanding some local
      histological changes.

PMID- 7807175
TI  - Pharmacokinetics of intrathecal 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2
      chloroethyl)-3-nitrosourea hydrochloride in rats.
AB  - The pharmacokinetics of intrathecal 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3
      (2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) were studied in female Wistar
      rats by macroscopical autoradiography using 14C labeled ACNU. In normal rats,
      ACNU rapidly distributed in the subarachnoid space and ventricles after
      intracisternal administration. Diffusional transport into the brain tissue was
      limited to a depth of 1 or 2 mm from the cerebrospinal fluid (CSF) surface of the
      brain. Clearance of ACNU from the CSF space and brain was relatively fast and the
      half time of ACNU concentration at the cortical or ventricular surface was 10
      min. In rats with leptomeningeal tumor induced by intracisternal inoculation of
      Walker 256 carcinosarcoma cells, the distribution pattern of ACNU after
      intracisternal administration was essentially the same as in normal rats until
      the tumor had grown in the subarachnoid space to form more than 10 or 20 layers
      of tumor cells. ACNU was distributed in the tumor as well. When the tumor had
      grown to form masses in the subarachnoid space, ACNU failed to penetrate to more
      than a depth of 1 or 2 mm from the tumor surface. Our results suggest that
      intrathecal ACNU administration may have no, or minor side effects on the brain
      and that it can eliminate floating or thin layered tumor cells in the
      subarachnoid space but not bulky tumors.

PMID- 7807176
TI  - Anti-proliferative effects of TNP-470 on human malignant glioma in vivo: potent
      inhibition of tumor angiogenesis.
AB  - A novel angiogenesis inhibitor TNP-470 was investigated for its anti-tumor
      activity against malignant gliomas both in vitro and in vivo. TNP-470
      cytostatically inhibited the growth in all of the seven glioma cell lines in
      culture including anticancer drug resistant cells. The 50% inhibitory
      concentrations (IC50) of these glioma cell lines were 10 to 30 micrograms/ml and
      they were 10 to 20 times higher than IC50 of normal endothelial cells. TNP-470
      (30 mg/kg, i.p., every other day) also significantly inhibited the tumor growth
      of T98G-transplanted nude mice. Microscopically, tumor vessels after the
      treatment of the tumor-bearing mice with TNP-470 became fewer in number and
      smaller in diameter than those without treatment. Furthermore, there appeared
      extensive necrotic areas in the tumor with TNP-470. These results indicate that
      TNP-470 is a potent angiogenesis inhibitor for malignant gliomas. In addition,
      the studies of labeling index of BrdU and Ki67 suggest that TNP-470 may act
      mainly on tumor endothelial cells, thus resulting in reduction of the tumor
      growth.

PMID- 7807178
TI  - Efficient transfection of human interferon-beta gene to human glioma cells by
      means of cationic multilamellar liposomes coupled with a monoclonal antibody
      [corrected].
AB  - We have been devoting our efforts to develop the useful liposomes that have high
      potentials of gene transfer and we aim human gene therapy for malignant glioma
      with cytokine genes. In our previous study, we prepared our original reverse
      phase evaporation vesicles (REV) by an improved procedure of reverse-phase
      evaporation method. However, this procedure was very complicate. In this paper, a
      simple procedure for the preparation of cationic multilamellar vesicles (MLV) was
      introduced, and efficient expression and growth-inhibitory effect of MLV with
      entrapped human interferon-beta gene to glioma cells was comparable to that
      obtained with REV. Considering the present experiments, MLV seem to be more
      preferable for clinical application.

PMID- 7807177
TI  - Negative effects of wild-type p53 and s-Myc on cellular growth and tumorigenicity
      of glioma cells. Implication of the tumor suppressor genes for gene therapy.
AB  - Human (U251, U87, U343) and rat glioma cell lines (C6, 9L) were examined by the
      reverse transcriptase-polymerase chain reaction and subsequent nucleotide
      sequencing analysis to see whether they express wild type (wt)-p53 or mutated
      form (mut)-p53 messages. Results showed that U87, U343, and C6 cells expressed wt
      p53 messages whereas U251 and 9L cells expressed mut-p53 messages. All these cell
      lines were transfected with wt-p53 cDNA or the s-myc gene linked to the mouse
      mammary tumor virus (MMTV) promoter. Of several G418-resistant clones obtained
      from each transfection, a few expressed the s-Myc or wt-p53 proteins. Independent
      of mutations in the intrinsic p53 gene, the cellular growth in vitro and
      tumorigenicity in nude mice of these clones were drastically suppressed, the
      extent of suppression being correlated with the expression level of the
      transfected gene. Flow-cytometric analysis demonstrated that both p53 and s-Myc
      arrested the cell cycle at the G1/S boundary. These data suggest that these genes
      having negative effects on tumor cell proliferation could be used in gene therapy
      of gliomas, which are caused by alteration of the p53 gene or by some other
      genetic change.

PMID- 7807179
TI  - Development of an in vitro extracellular matrix assay for studies of brain tumor
      cell invasion.
AB  - Invasion of brain by tumor cells is an inherent feature of the malignant
      phenotype. Assays to quantitate invasiveness should provide a powerful tool to
      investigate this phenomenon. We have developed a modified in vitro assay to
      measure tumor cell invasion, attachment, and chemotaxis using a barrier of the
      complex basement membrane Matrigel on gelatin-coated filters. Within 5 hours,
      7.8% of U251MGp and 2.6% of SF126 human malignant glioma cells invaded the
      Matrigel and filter, compared with 0.8% of normal human leptomeningeal cells. The
      extent of invasion was directly proportional to incubation time and filter pore
      size and inversely proportional to the Matrigel concentration. Cells from
      exponentially growing U251MGp cultures invaded more readily (10.9%) than cells
      from plateau-phase cultures (2.3%); however, labeling studies with
      bromodeoxyuridine showed that quiescent cells and rapidly dividing cells were
      equally capable of invading. This suggests that the mechanisms underlying
      invasion by malignant glioma cells are distinct from those underlying
      proliferation and indicates the need for therapy aimed specifically at invasive
      behavior. In a practical application of this assay to test a potential anti
      invasive strategy, monoclonal antibodies to the beta subunit of an integrin
      receptor mediating attachment to the extracellular matrix inhibited invasion by
      U251MGp cells in a dose-dependent manner. This assay should allow evaluation of
      the cellular and molecular basis of brain tumor progression and perhaps aid the
      development of rationally designed drugs that limit tumor invasion. It may also
      allow prediction of the clinical behavior of neoplasms in individual patients.

PMID- 7807180
TI  - Blood-brain barrier changes following intracerebral injection of human
      recombinant tumor necrosis factor-alpha in the rat.
AB  - Human recombinant tumor necrosis factor-alpha (rTNF-alpha) was administered to
      normal Fischer 344 rats by stereotaxic intracerebral (IC) injection. Animals
      receiving a single injection of either 6 x 10(4) U rTNF-alpha or an equivalent
      volume of excipient (vehicle) in their right parietal lobe. In order to
      demonstrate any effects rTNF-alpha might have on the blood-brain barrier (BBB),
      two studies were conducted, one employing exogenous horseradish peroxidase
      (HRP,44 kD) as a tracer of BBB permeability and the other using endogenous IgG
      (150 kD). Rats given rTNF-alpha showed transitory BBB permeability to HRP by 24
      hours post-injection; this BBB compromise was determined to be no longer than 60
      hours. In the other study, IgG was seen to cross the BBB by 48 hours post-rTNF
      alpha injection. Alternatively, rats injected IC with excipient showed only
      limited BBB opening as a result of injection-induced trauma. We conclude that
      human rTNF-alpha, injected IC into normal rats triggers a temporary breakdown in
      BBB integrity which begins sometimes between 12 and 24 hours post-injection, is
      large enough to permit macromolecules of at least 150 kD to pass, and resolves by
      72 hours post-injection.

PMID- 7807181
TI  - Development of a non-selecting, non-perturbing method to study human brain tumor
      cell invasion in murine brain.
AB  - The infiltrative nature of glial and some meningeal neoplasms is responsible for
      the failure of surgical removal and high recurrence rate of these tumors.
      Modeling of this process in vitro and in vivo will lead to a better understanding
      of the pathophysiology of this process and identify targets for novel therapy
      directed towards this phenotype. We present the results of the development and
      refinement of two model systems of tumor invasion: one in vitro barrier assay
      using the basement membrane extract Matrigel, and one in vivo where molecular
      detection of tumor cells allows single cell discrimination by in situ
      hybridization histochemistry. These techniques have strong correlations which
      validate their utility as measures of nervous system tumor invasion.

PMID- 7807182
TI  - Activated monocytes kill malignant brain tumor cells in vitro.
AB  - The purpose of our study was to investigate the susceptibility of human
      glioblastoma multiforme (GBM) cells to lysis by human peripheral-blood monocytes
      following activation with biological response modifiers (BRM) and to lysis by
      various BRMs directly. Cytotoxic effects were determined using a monocyte-/BRM
      mediated tumor cytotoxicity assay. Human peripheral-blood monocytes from healthy
      donors were activated in vitro by incubation for 24 h with different BRMs such as
      gamma- and beta-interferon (gamma, beta-IFN), lipopolysaccharide (LPS),
      muramyldipeptide (MDP) and tumor necrosis factor-alpha (TNF-alpha) in varying
      concentrations and combinations. Seven human GBM cell lines as well as an
      adenocarcinoma brain metastasis cell line and a malignant melanoma cell line
      served as target cells. Radiolabeled target cells were cocultivated with
      activated monocytes or with BRMs directly. Cytotoxicity was calculated after 72 h
      of cocultivation. High levels of cytotoxicity were mediated by monocytes
      activated with beta-IFN in six out of eight brain tumor cell lines and with TNF
      alpha in five cell lines. The combination of two BRMs, in particular the
      combination of gamma-IFN + beta-IFN and gamma-IFN + TNF-alpha, was associated
      with an enhanced monocyte mediated lysis exceeding LPS control, whereas the
      combination of gamma-IFN + MDP was very effective against the metastasis cell
      line. Monocyte-mediated cytotoxicity against tumor target cells was up to ten
      fold higher than direct cytotoxicity of soluble BRMs. Our data indicate that BRM
      stimulated peripheral-blood monocytes exert cytotoxic properties against human
      glioblastoma cells in vitro, which exceed those of BRMs alone up to ten fold. The
      higher tumoricidal activities observed after stimulation with combined BRMs
      suggest mutual promoting mechanisms of BRMs acting on the stimulation of lyctic
      activity in human peripheral blood monocytes.

PMID- 7807183
TI  - Detection of Eber-1 RNA in primary brain lymphomas in immunocompetent and
      immunocompromised patients.
AB  - Tissue from primary central nervous system lymphoma (PCNSL) which developed in
      five patients with acquired immuno deficiency syndrome (AIDS), nine patients
      without immunodeficiency, and two Epstein-Barr virus (EBV)-positive control cell
      lines (B95-8 and Raji) were examined for the presence of EBER-1 RNA. The tissues
      were hybridized with digoxigenin-labeled sense or anti-sense EBER-1 riboprobes.
      In all five AIDS-related PCNSLs, strong hybridization signals were found with the
      EBER-1 anti-sense probe. Signals could be eliminated by preincubation of the
      tissues with RNase-A. Hybridization with the EBER-1 sense probe showed no signal.
      All PCNSLs from immunocompetent patients (five paraffin-embedded, four frozen)
      showed no hybridization signals with EBER-1 sense or antisense probe but good
      hybridization signals with probes to immunoglobulin kappa or lambda light chain
      indicating RNA preservation. The paraffin-embedded B95-8-positive control cell
      line showed positive hybridization in most cells with the anti-sense EBER-1
      probe, and up to one percent of the cells had a weak signal with the sense probe.
      Most Raji cells showed a uniform signal with the anti-sense EBER-1 probe only. We
      conclude that, PCNSLs that arise in AIDS patients are associated with latent EBV
      infections, whereas PCNSLs from immunocompetent patients are not indicating a
      probable role for EBV in pathogenesis of these tumors.

PMID- 7807185
TI  - Immunotoxin therapy of leptomeningeal neoplasia.
AB  - Malignant tumors of the central nervous system can result from metastatic
      dissemination of a variety of cancers. Percutaneous intracisternal injection of
      an anti-idiotype monoclonal antibody (M6) ricin immunotoxin was shown to be
      moderately effective in prolonging the survival of tumor bearing animals
      supporting the use of immunotoxins for the treatment of central nervous system
      neoplasia (Zovickian J and Youle R.J. J. Neurosurg 68: 767, 1988). This report
      describes a method that significantly improves the survival of immunotoxin
      treated Strain 2 guinea pigs in a syngeneic animal model of leptomeningeal
      neoplasia. Strain 2 guinea pigs, implanted with subarachnoid catheters, received
      three courses of treatment with an (M6)-intract ricin immunotoxin following
      intracisternal inoculation of L2C leukemia tumor cells. Animals were treated with
      three to four micrograms of immunotoxin in three divided doses. This was found to
      be less toxic and more effective than single bolus administration of immunotoxin.
      These results demonstrate that a permanent indwelling catheter in this animal
      model facilitates multiple dose delivery of immunotoxin therapy allowing the
      assessment of various treatment schedules and the achievement of enhanced
      therapeutic effect. Furthermore, these results support the continued evaluation
      of immunotoxins for the treatment of central nervous system neoplasia.

PMID- 7807184
TI  - Lack of association of human polyomaviruses with human brain tumors.
AB  - Brain tumors, primarily glioblastoma multiforme, were examined for the presence
      of BKV DNA. DNAs extracted from 33 fresh-frozen tumors and from an additional 47
      paraffin-embedded tumor tissues were tested for BKV sequences using two different
      primer pairs. One primer pair amplified highly conserved sequences in the early
      region coding for BKV and JCV T antigens. The other primer pair amplified the
      regulatory region of BKV-IR, a variant previously associated with human brain
      tumors. None of the tumors were positive for BKV or JCV DNA.

PMID- 7807186
TI  - Characterization of the influence of anti-hormone and/or anti-growth factor
      neutralizing antibodies on cell clone architecture and the growth of human
      neoplastic astrocytic cell lines.
AB  - The influence of five anti-hormone and/or anti-growth factor neutralizing
      antibodies on the in vitro proliferation of four human astrocytic tumor cell
      lines (U87, U138, U373, H4) is quantitatively described by means of a new tool
      which makes it possible to evaluate cell growth and cell clone architecture
      concomitantly. This tool relies upon the combined use of the digital cell image
      analyses of Feulgen-stained nuclei and the Delaunay and Voronoi mathematical
      triangulation and paving techniques. Of the five anti-hormone and/or anti-growth
      factors tested here, the anti-luteinizing hormone-releasing hormone (LHRH)
      antibody induced the most marked perturbation in the U138 and U373 cell lines,
      whereas this role was played by the anti-epidermal growth factor (EGF) antibody
      in the U87 and H4 cell lines. The anti-gastrin (G) antibody significantly
      modified the growth and/or cell clone architecture of the U138, U87 and H4 cell
      lines, as did the anti-transforming growth factor alpha (TGFalpha) antibody. The
      anti-transforming growth factor beta (TGFbeta) antibody modified the growth
      and/or cell clone architecture of the four cell lines under study. If the five
      antibodies are taken into consideration, the results strongly suggest that four
      (the anti-G, the anti-EGF, the anti-LHRH and the anti-TGFalpha) act as inhibitory
      agents on some glioma cell line proliferation, while the fifth one, i.e. the anti
      TGFbeta, act as a stimulator of cell proliferation, perhaps by abrogating the
      inhibitory effects of TGFbeta on proliferation. A comparison of cell growth data
      with cell clone architecture characteristics provided further evidence of some
      specific influence exercised by a given hormone and/or growth factor on glioma
      cell proliferation. Indeed, the anti-LHRH antibody caused the most pronounced
      perturbations in the U138 and U373 cell clone architecture; this feature was
      observed in the H4 cell line and, to a lesser extent in the U87 one after the
      anti-EGF antibody had been used.

PMID- 7807188
TI  - Chemotherapy of primary brain tumors.

PMID- 7807187
TI  - The application of 5-bromodeoxyuridine in the management of CNS tumors.
AB  - A variety of clinical reports have described the application of the
      bromodeoxyuridine labeling index as an adjunct to conventional pathological
      examination of CNS tumors. This index has proven useful in predicting the
      clinical outcome associated with many such tumors. Furthermore, because of its
      efficacy as a radiosensitizing agent, bromodeoxyuridine (and the closely related
      iododeoxyuridine) has been used in combination with radiation therapy for
      malignant glial neoplasms, with some encouraging results. Although most studies
      suggest that bromodeoxyuridine is safe, there is evidence that this compound does
      have potential side-effects, including the observation that it is a mutagen and
      carcinogen in some experimental systems. A number of new alternative approaches
      for predicting the clinical outcome of CNS tumors has been developed based on an
      increased understanding of their molecular biology. However, until such
      approaches are better characterized, the clinical application of
      bromodeoxyuridine will continue to play an important role in predicting the
      clinical behavior of many CNS tumors.

PMID- 7807189
TI  - The basis for current treatment recommendations for malignant gliomas.
AB  - Although primary brain tumors represent an important cause of cancer related
      mortality in the United States, advances in the treatment of these tumors has
      been slow and has generally lagged behind that of most systemic tumors. One of
      the major reasons for this is the paucity of well conducted, prospective
      radiation and chemotherapy trials. For the brain tumor trials that have been
      conducted, small patient numbers, heterogeneous patient populations, and non
      uniformity of response criteria, have made the current clinical data base
      difficult to interpret. Data from several prospective, multi-institutional
      randomized trials have defined a role for radiation therapy in the treatment of
      malignant gliomas and on-going trials will help define refinements in technique.
      Although there does appear to be a place for the use of chemotherapy in the
      treatment of a subgroup of patients with malignant gliomas, its role for the
      majority of patients remains unclear. Only through better understanding of the
      biology of these tumors, more effective therapies, and the implementation of
      better clinical trial design can we hope to make significant progress in the
      treatment of malignant gliomas.

PMID- 7807191
TI  - New agents in the treatment of primary brain tumors.
AB  - A review of single agent trials of cytotoxic agents in adults with high grade
      gliomas is presented. The rationale for testing these agents in patients with
      brain tumors was variable and is discussed. The criteria to evaluate responses
      were also variable ranging from subjective evaluation of clinical improvement
      with a stable radiographic assessment to the same objective response criteria
      utilized for solid tumors. Trials of agents specifically designed for brain
      tumors such as AZQ and spiromustine have been disappointing. There are
      encouraging results being seen in early trials of newer agents which await
      confirmation in larger trials but which hold promise for improving the
      disappointing results seen so far with chemotherapy in primary brain tumors.

PMID- 7807192
TI  - High dose chemotherapy for the treatment of malignant brain tumors.
AB  - Conventional treatment of malignant high grade gliomas includes maximal resection
      followed by external beam radiotherapy. The addition of adjuvant chemotherapy has
      provided little improvement in the median duration of survival for these
      patients, particularly those patients with glioblastoma multiforme. The failure
      of conventional dose chemotherapy to improve the outcome of patients with high
      grade brain tumors has led several investigators to utilize high dose
      chemotherapy in order to overcome the limited benefit seen with conventional dose
      therapy which is due to intrinsic drug resistance as well as the impermeability
      of blood brain barrier. The majority of published studies utilizing this approach
      suggest that the addition of high dose chemotherapy with bone marrow transplant
      is of marginal benefit. However, most of these trials include small numbers of
      patients with advanced, refractory disease. A few trials have been reported
      utilizing high dose therapy in an adjuvant setting and the data from these
      studies are somewhat more promising. This review will analyze these studies and
      also discuss possible modifications of this approach in order to improve this
      aggressive treatment for patients who otherwise would have a dismal prognosis.

PMID- 7807190
TI  - A critique of the role of the blood-brain barrier in the chemotherapy of human
      brain tumors.
AB  - There is general agreement that most chemotherapy agents achieve only relatively
      low concentrations in the normal central nervous system, that the blood-brain
      barrier is variably disrupted in malignant brain tumors, and that the
      concentration of chemotherapy drugs in the brain adjacent to tumor is
      intermediate between concentrations achieved in brain tumors vs normal brain.
      However, there is substantial controversy regarding the role of the blood-brain
      barrier in resistance to chemotherapy of intracerebral tumors. Many chemotherapy
      agents achieve concentrations in brain tumors that are comparable to those in
      extracerebral tumors, and drugs that cross the intact blood-brain barrier only
      poorly may be active against intracerebral tumors. Furthermore, the hypothesis
      that the brain is a pharmacological sanctuary where metastases may grow while
      tumor is responding in other parts of the body may be flawed: there are only 2 or
      3 types of malignancies (out of all those that are sensitive to chemotherapy) in
      which the risk of isolated central nervous system relapse is moderately high, and
      even in these 2 or 3, effective central nervous system prophylaxis has minimal or
      no impact on overall survival. Furthermore, drugs that cross the BBB do not
      appear to be more effective than other drugs at reducing the risk of brain
      metastases, and brain metastases at the time of diagnosis do not necessarily
      convey a worse prognosis than metastases to various other sites. While average
      drug concentrations in brain adjacent to tumor are lower than those within brain
      tumors, very small numbers of tumor cells may be capable of inducing local
      leakiness in blood vessels, and there is little information on drug
      concentrations achieved in individual tumor cells within the brain adjacent to
      tumor. Furthermore, any limitation of uptake of drugs into brain tumors could be
      at least partially due to increased tissue pressure within tumors rather than
      being due to blood-brain barrier phenomena. This distinction could be important,
      since strategies that one might use to increase drug delivery to brain tumors
      might differ depending on whether the reduced delivery were due to barrier
      phenomena vs blood flow phenomena. The role of the blood-brain barrier in
      resistance of intracerebral tumors to chemotherapy remains unclear: while it may
      well play some role (and perhaps even a major one), self-fulfilling prophecies
      and unintentional bias in data selection and interpretation may have previously
      made it appear more important than it actually is.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7807193
TI  - Drug resistance in brain tumors.
AB  - Resistance to chemotherapy in brain tumors is complex and may involve multiple
      mechanisms. For commonly used drugs, such as nitrosoureas and platinum compounds,
      major mechanisms may involve increaded DNA repair or removal of the drug-DNA
      adducts. For water soluble nitrosoureas and also for platinum compounds, other
      mechanisms, such as alteration in drug transport, may be important. Another major
      mechanism may involve glutathione and glutathione-S-transferase pathways. For
      vinca alkaloids and epipodophyllotoxins p-glycoprotein mediated MDR appears to be
      the major feature in drug resistance. In addition, alteration of tubulin and
      topoisomerase II have been described in resistance to vinca alkaloids and
      epipodophyllotoxins respectively. Recently, increased multidrug resistance
      associated protein gene expression has been found in glioma cells and brain tumor
      samples; its clinical significance requires further investigation.

PMID- 7807194
TI  - Primary central nervous system lymphoma.

PMID- 7807195
TI  - Translation invariance in the responses to faces of single neurons in the
      temporal visual cortical areas of the alert macaque.
AB  - 1. The responses of single neurons in the inferior temporal cortex and the cortex
      in the banks of the anterior part of the superior temporal sulcus of three awake,
      behaving macaques were recorded during a visual fixation task. Stimulus images
      subtending 17 or 8.5 degrees were presented in the center of the display area,
      and fixation was either at the center of the display area, or at one of four
      positions that were on the stimulus, or several degrees off the edge of the test
      stimulus. The experiments were performed with face-selective cells, and the
      responses were compared for fixation at each position for both effective and
      noneffective face stimuli for each cell. 2. The firing rates of most neurons to
      an effective image did not significantly alter when visual fixation was as far
      eccentric as the edge of the face, and they showed only a small reduction when
      the fixation point was up to 4 degrees from the edge of the face. Moreover,
      stimulus selectivity across faces was maintained throughout this region of the
      visual field. 3. The centers of the receptive fields of the cells, as shown by
      the calculated "centers of gravity," were close to the fovea, with almost all
      being within 3 degrees of the fovea. 4. The receptive fields of the cells
      typically crossed the vertical midline for at least 5 degrees. 5. Information
      theory procedures were used to analyze the spike trains of the visual neurons.
      Nearly six times more information was carried by these neurons' firing rate about
      the identity of an image than about its position in the visual field. Thus the
      information theory analysis showed that the responses of these neurons reflected
      information about which stimulus had been seen in a relatively translation
      invariant way. 6. Principal component analysis showed that principal component 1
      (PC1) is related primarily to firing rate and reflected information primarily
      about stimulus identity. (For identity PC2 added only 14% more information to
      that contained in PC1.) Principal component 2 (PC2) was more closely related to
      neuronal response latencies, which increased with increasing eccentricity of the
      image in the visual field. PC2 reflected information about the position of the
      stimulus in the visual field, in that PC2 added 109% more information to that
      contained in PC1 about the position of the stimulus in the visual field.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7807196
TI  - Response selectivity for multiple dimensions of frequency sweeps in the pallid
      bat inferior colliculus.
AB  - 1. While hunting, the pallid bat uses passive sound localization at low
      frequencies to find terrestrial prey, and echolocation for general orientation.
      It must therefore process two different types of acoustic input at the same time.
      The pallid bat's echolocation pulse is a downward frequency-modulated (FM) sweep
      from 60 to 30 kHz. This study examined the response selectivity of single neurons
      in the pallid bat's central nucleus of the inferior colliculus (ICC) for FM
      sweeps, comparing the response properties of the high-frequency population, tuned
      to the biosonar pulse, with the low-frequency population, tuned below the pulse.
      The working hypothesis was that the high-frequency population would exhibit a
      response selectivity for downward FM sweeps that was not present in the low
      frequency population. 2. Neurons were tested for their selectivity for FM sweep
      direction, duration, frequency range and bandwidth, and rate of frequency change.
      The extent to which they responded exclusively to tones, noise, and FM sweeps was
      also examined. Significant differences in the response properties of neurons in
      the two populations were found. In the low-frequency population, all neurons
      responded to tones, but only 50% responded to FM sweeps. Only 23% were selective
      for sweep direction. In the high-frequency population, all neurons responded to
      FM sweeps, but 31% did not respond to tones. Over one-half of this population was
      selective for sweep direction, and of those that were selective, all preferred
      the downward sweep direction of the biosonar pulse. A large percentage (31%)
      responded exclusively to downward sweeps, and not to tones or upward sweeps. None
      of the cells in either population responded to noise, or did so only at very high
      relative thresholds. 3. Both populations contained neurons that were selective
      for short stimulus durations that approximated the duration of the biosonar
      pulse, although the percentage was greater in the high-frequency population (58%
      vs. 20%). In the high-frequency population, 31% of the neurons tested for
      duration responded exclusively to both the sweep direction and duration of the
      biosonar pulse. 4. Downward FM-selective neurons, with one exception, were
      generally insensitive to the rate of frequency change of the FM sweep, as well as
      the frequency range and bandwidth of the sweep. They responded similarly to both
      the full 60- to 30-kHz sweep and to 5-kHz bandwidth portions of the full
      sweep.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7807197
TI  - Azimuthal receptive fields are shaped by GABAergic inhibition in the inferior
      colliculus of the mustache bat.
AB  - 1. In this study we examine the effects of GABAergic inhibition on the response
      properties and the constructed azimuthal receptive fields of 54
      excitatory/inhibitory (EI) neurons tuned to 60 kHz in the inferior colliculus of
      the mustache bat. The constructed azimuthal receptive fields predict the spike
      counts that would be evoked by different intensities of 60-kHz sounds presented
      from each of 13 azimuthal locations in the frontal sound field. 2. Action
      potentials were recorded with a micropipette attached to a multibarrel glass
      electrode. Bicuculline, an antagonist specific for gamma-aminobutyric acid-A
      (GABAA) receptors, was iontophoretically applied through the multibarrel
      electrode. Both monaural and binaural response properties were initially recorded
      at a variety of interaural intensity disparities (IIDs) and absolute intensities,
      and the same response properties were subsequently assessed while GABAergic
      inhibition was blocked by bicuculline. Azimuthal receptive fields both before and
      during the application of bicuculline were constructed from response properties
      obtained with earphones after correcting for the directional properties of the
      ear and the IIDs generated by 60-kHz sounds presented from a variety of azimuthal
      locations. 3. Bicuculline had virtually no effect on either the monaural or
      binaural properties of 19 cells (35%). The constructed azimuthal receptive fields
      of these cells were also unaffected by bicuculline. Presumably the properties of
      these cells were formed in a lower nucleus, most likely the contralateral lateral
      superior olive (LSO), and were imposed on the collicular cell via the crossed
      projection from the LSO to the inferior colliculus, which is known to be
      excitatory. 4. In more than half of the neurons (65%) GABAergic inhibition
      influenced one or more features of the cell's response properties and thus its
      azimuthal receptive field. Some response properties were formed in the colliculus
      through GABAergic inhibition, whereas others appear to have been shaped initially
      in a lower nucleus and then further modified by GABAergic inhibition in the
      inferior colliculus. Moreover, a number of features of GABAergic inhibition that
      acted on inferior collicular cells were evoked by stimulation of the
      contralateral (excitatory) ear, whereas other features were influenced by
      stimulation of the ipsilateral (inhibitory) ear. 5. In 20 cells (37%) blocking
      GABAergic inhibition reduced or abolished the inhibition evoked by the
      ipsilateral ear. The receptive fields of cells in which the ipsilaterally evoked
      inhibition was reduced by bicuculline expanded further into the ipsilateral sound
      field than they did before bicuculline.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7807198
TI  - Synchronization properties of spindle oscillations in a thalamic reticular
      nucleus model.
AB  - 1. We address the hypothesis of Steriade and colleagues that the thalamic
      reticular nucleus (RE) is a pacemaker for thalamocortical spindle oscillations by
      developing and analyzing a model of a large population of all-to-all coupled
      inhibitory RE neurons. 2. Each RE neuron has three ionic currents: a low
      threshold T-type Ca2+ current (ICa-T), a calcium-activated potassium current
      (IAHP) and a leakage current (IL). ICa-T underlies a cell's postinhibitory
      rebound properties, whereas IAHP hyperpolarizes the neuron after a burst. Each
      neuron, which is a conditional oscillator, is coupled to all other RE neurons via
      fast gamma-aminobutyric acid-A (GABAA) and slow GABAB synapses. 3. For generating
      network oscillations IAHP may not be necessary. Synaptic inhibition can provide
      the hyperpolarization for deinactivating ICa-T that causes bursting if the
      reversal potentials for GABAA and GABAB synapses are sufficiently negative. 4. If
      model neurons display sufficiently powerful rebound excitability, an isolated RE
      network of such neurons oscillates with partial but typically not full synchrony.
      The neurons spontaneously segregate themselves into several macroscopic clusters.
      The neurons within a cluster follow the same time course, but the clusters
      oscillate differently from one another. In addition to activity patterns in which
      clusters burst sequentially (e.g., 2 or 3 clusters bursting alternately), a two
      cluster state may occur with one cluster active and one quiescent. Because the
      neurons are all-to-all coupled, the cluster states do not have any spatial
      structure. 5. We have explored the sensitivity of such partially synchronized
      patterns to heterogeneity in cells' intrinsic properties and to simulated
      neuroelectric noise. Although either precludes precise clustering, modest levels
      of heterogeneity or noise lead to approximate clustering of active cells. The
      population-averaged voltage may oscillate almost regularly but individual cells
      burst at nearly every second cycle or less frequently. The active-quiescent state
      is not robust at all to heterogeneity or noise. Total asynchrony is observed when
      heterogeneity or noise is too large, e.g., even at 25% heterogeneity for our
      reference set of parameter values. 6. The fast GABAA inhibition (with a reversal
      potential more negative than, say, -65 mV) favors the cluster states and prevents
      full synchrony. Our simulation results suggest two mechanisms that can fully
      synchronize the isolated RE network model. With GABAA removed or almost totally
      blocked, GABAB inhibition (because it is slow) can lead to full synchrony, which
      is partially robust to heterogeneity and noise.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7807199
TI  - Electrophysiology of globus pallidus neurons in vitro.
AB  - 1. We investigated the electrical properties of globus pallidus neurons
      intracellularly using brain slices from adult guinea pigs. Three types of neurons
      were identified according to their intrinsic electrophysiological properties. 2.
      Type I neurons (59%) were silent at the resting membrane level (-65 +/- 10 mV,
      mean +/- SD) and generated a burst of spikes, with strong accommodation, to
      depolarizing current injection. Calcium-dependent low-frequency (1-8 Hz) membrane
      oscillations were often elicited by membrane depolarization (-53 +/- 8 mV). A low
      threshold calcium conductance and an A-current were also identified. The mean
      input resistance of this neuronal type was 70 +/- 22 M omega. 3. Type II neurons
      (37%) fired spontaneously at the resting membrane level (-59 +/- 9 mV). Their
      repetitive firing (< or = 200 Hz) was very sensitive to the amplitude of injected
      current and showed weak accommodation. Sodium-dependent high-frequency (20-100
      Hz) subthreshold membrane oscillations were often elicited by membrane
      depolarization. This neuronal type demonstrated a low-threshold calcium spike and
      had the highest input resistance (134 +/- 62 M omega) of the three neuron types.
      4. Type III neurons (4%) did not fire spontaneously at the resting membrane level
      (-73 +/- 5 mV). Their action potentials were characterized by a long duration
      (2.3 +/- 0.6 ms). Repetitive firing elicited by depolarizing current injection
      showed weak or no accommodation. This neuronal type had an A-current and showed
      the lowest input resistance (52 +/- 35 M omega) of the three neuron types. 5.
      Stimulation of the caudoputamen evoked inhibitory postsynaptic potentials (IPSPs)
      in Type I and II neurons. In Type II neurons the IPSPs were usually followed by
      rebound firing. Excitatory postsynaptic potentials and antidromic responses were
      also elicited in some Type I and II neurons. The estimated conduction velocity of
      the striopallidal projection was < 1 m/s (Type I neurons, 0.49 +/- 0.37 m/s; Type
      II neurons, 0.33 +/- 0.13 m/s).

PMID- 7807200
TI  - Inhibition and facilitation of different nocifensor reflexes by spatially remote
      noxious stimuli.
AB  - 1. Noxious stimuli have been shown to produce a diffuse inhibition of
      nociresponsive neurons in the spinal and trigeminal dorsal horns. The present
      study sought to extend these electrophysiological studies of diffuse noxious
      inhibitory controls (DNIC) by determining the effect of a spatially remote
      noxious stimulus on behavioral measures of nociception. Changes in latency for
      hindpaw withdrawal and tail flick reflexes were measured in lightly halothane
      anesthetized or awake, spinally transected rats before, during, and after
      application of a spatially remote noxious stimulus. 2. Surprisingly, in no case
      did application of a spatially remote noxious stimulus inhibit the hindpaw
      withdrawal reflex. The latency for this reflex was either reduced or did not
      change when the tail or contralateral hindpaw was placed in hot water (50 degrees
      C) or when a noxious pinch was applied to the ear. In contrast, the latency for
      the tail flick reflex was consistently increased when the hindpaw was placed in
      hot water. Both the hindpaw reflex facilitation and the tail flick reflex
      inhibition produced by a noxious conditioning stimulus were attenuated in
      spinally transected rats indicating supraspinal modulation of both reflexes. 3.
      In addition, and consistent with the work of others, placing the tail in hot
      water reduced the evoked activity of convergent neurons in both the trigeminal
      and lumbar spinal dorsal horns. Thus inhibition of the activity of nociresponsive
      neurons in the dorsal horn is consistent with inhibition of the tail flick
      reflex, but not with facilitation of the hindpaw withdrawal reflex.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7807201
TI  - Pronounced changes in the activity of nociceptive modulatory neurons in the
      rostral ventromedial medulla in response to prolonged thermal noxious stimuli.
AB  - 1. Brain regions that inhibit nociception can be activated by various
      environmental stimuli, including prolonged noxious stimuli. The present study
      tested the effect of such a prolonged noxious stimulus on the activity of
      nociceptive modulatory neurons in the rostral ventromedial medulla (RVM). These
      neurons, called ON- and OFF-cells because of their respective burst and pause in
      activity associated with nocifensor reflexes, have been shown to facilitate and
      inhibit nociception, respectively. 2. Single-unit activity of ON- and OFF-cells
      was assessed in lightly halothane- or barbiturate-anesthetized rats exposed to
      prolonged noxious heat (50 degrees C water). This prolonged noxious stimulus
      caused an increase in ON-cell and a decrease in OFF-cell activity regardless of
      anesthetic (halothane or barbiturate) or stimulus location (hindpaw or tail). 3.
      Surprisingly, and despite the consistent changes in RVM cell activity, the
      prolonged noxious stimulus caused different effects depending on the reflex used
      to assess nociception. The hindpaw withdrawal reflex was facilitated when the
      tail was immersed in hot water, whereas the tail flick reflex was inhibited when
      the hindpaw was immersed in hot water (see preceding manuscript). Lidocaine
      inactivation of the RVM shortened the latency for both reflexes but had no effect
      on tail flick inhibition produced by the noxious conditioning stimulus. In
      contrast, lidocaine inactivation of the RVM completely reversed the hindpaw
      reflex facilitation produced by tail heat, indicating the involvement of RVM ON
      cells in facilitation of this reflex. 4. These data demonstrate that RVM neurons
      respond in a consistent manner to noxious stimuli whether applied for a brief or
      prolonged time: ON-cell activity increases and OFF-cell activity decreases.
      Moreover, the activation of RVM ON-cells produced by a noxious stimulus is
      sufficient to enhance some nocifensor reflexes, whereas neural structures other
      than the RVM appear to mediate the antinociceptive effects produced by a
      prolonged noxious stimulus.

PMID- 7807202
TI  - Arm position constraints when throwing in three dimensions.
AB  - 1. Overarm throwing is a skilled multijoint movement with potentially many
      degrees of freedom. Considering only the arm > or = 7 degrees of freedom are
      involved (shoulder 3, elbow 2, wrist 2). For each arm segment 3 degrees of
      freedom are potentially required to specify its angular position (orientation) at
      any moment during a throw. Simplification of the control problem for the CNS
      would occur if there were constraints on these degrees of freedom. The objective
      was to determine whether such constraints exist at ball release when throwing at
      targets in different directions using only the arm. 2. The angular positions in
      three dimensions of the distal phalanx of the middle finger, the hand, the
      forearm, and the upper arm were simultaneously recorded with search coils as
      subjects sat with a fixed trunk and threw balls at nine targets in an approximate
      +/- 40 degree work space. Ball release was signaled by microswitches on the
      proximal and distal phalanges of the middle finger (proximal and distal
      triggers). 3. On throwing at any one target the hand at ball release adopted a
      similar orientation for each throw, i.e., for a particular vertical and
      horizontal angular position the hand adopted a similar torsional position. On
      throwing at targets throughout the work space, angular position (rotation)
      vectors describing hand positions in space at ball release were confined to a two
      dimensional surface rather than a three-dimensional volume. This constraint in
      hand torsion occurred near and at ball release but not throughout the entire
      throw. It was not due to mechanical factors because such a surface was not
      obtained when subjects deliberately twisted their arms when throwing. Thus at
      ball release during a "natural" throw the hand was constrained to 2 of its
      possible 3 angular degrees of freedom. 4. The same constraint was also found for
      finger, forearm, and upper arm angular positions in space at ball release as
      determined at both the proximal and distal triggers. A consequence is that at
      ball release the entire arm was constrained to 2 of its possible 7 degrees of
      freedom. 5. The two-dimensional position vector surface for each arm segment was
      similar to that obtained when pointing with a straight arm at the same targets.
      In both cases they showed torsion and were twisted like the surface obtained by
      rotations around the horizontal and vertical axes of a Fick gimbal. However, in
      some subjects the throwing surfaces were tilted from the vertical.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7807203
TI  - Hypoglossal neural activity during ingestion and rejection in the awake rat.
AB  - 1. The activity of 34 hypoglossal (mXII) neurons was characterized during the
      ingestion and rejection of gustatory stimuli in the awake rat. Intraoral
      infusions of water, sucrose, sodium chloride, or hydrochloric acid initiated
      ingestion responses; infusions of quinine monohydrochloride initiated rejection
      responses. Electromyographic (EMG) activity from three oropharyngeal muscles
      monitored the occurrence of lick cycles and swallows (ingestion) and gape cycles
      (rejection). In addition, the orofacial region was videotaped to provide an
      independent assessment of lingual and jaw movements in relation to neural
      activity. 2. EMG activity during lick and gape cycles was quantified by
      calculating the duration, magnitude, and peak time of muscle contractions. Lick
      and gape cycles produced highly differentiated patterns of activity from jaw
      opener (anterior digastric, AD), lingual protrudor (geniohyoid, GEN), and lingual
      retractor (styloglossus, STY) muscles. Lick cycles were characterized by an
      alternating two-phase sequence of protrusion-retraction; gape cycles by an
      initial coactivation of both lingual muscles (phase I), followed by a sequence of
      protrusion (phase II) and retraction (phase III). Contraction durations were
      significantly longer during gape cycles compared with lick cycles for the AD
      (Xlick +/- 59 ms; Xgape +/- 134 ms, means +/- SD), GEN (Xlick +/- 77 ms; Xgape +/
      200 ms), and STY (Xlick +/- 93 ms; Xgape +/- 220 ms) muscles. 3. Thirty-one out
      of 34 mXII neurons were functionally classified as protrudor- or retractor
      related by cross-correlating anterior digastric EMG activity with neural activity
      during licking. Fourteen out of 34 neurons were protrudor-related, 17/34 were
      retractor-related. These classifications were largely consistent with the results
      from an analysis of a subset of cells (n = 14) that directly compared neural
      activity with videotaped records of visible tongue movements. 4. The magnitude of
      mXII activity during ingestion and rejection was compared by determining the mean
      number of spikes per lick, gape, and swallow for each neuron. Five out of 14
      (36%) protrudor-related and 10/17 (59%) retractor-related cells had significant
      increases in activity during gape responses compared with the number of spikes
      per lick cycle. This increased activity of mXII neurons was consistent with the
      more robust lingual motor activity during the gape response. Two protrudor
      related and three retractor-related neurons showed significant decreases in
      activity during gape responses. Although a similar proportion of mXII neurons
      exhibited decreases in activity during swallows compared with licks (3 protrudor-
      and 1 retractor-related), fewer mXII neurons (1 protrudor- and 1 retractor
      related) showed increased activity during swallows.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7807204
TI  - Role of vagal afferents and spinal pathways modulating inhibition of bradykinin
      induced plasma extravasation by intrathecal nicotine.
AB  - 1. Nicotine, a major active component of tobacco smoke, has been shown to
      modulate the inflammatory response via both peripheral and central nervous system
      pathways. Recently we found that spinal intrathecal administration of nicotine
      dose-dependently inhibits bradykinin-induced plasma extravasation (BK-induced PE)
      in the knee joint of the rat and that the dose-response curve for the inhibition
      of BK-induced PE by intrathecal nicotine is shifted to the left, by six orders of
      magnitude, after surgical interventions in the abdominal cavity, which might have
      interrupted visceral afferents to the neuraxis. Therefore we focused, in this
      study, on the contribution of the vagal afferents to depression of BK-induced PE
      by intrathecal nicotine. Furthermore, the effect of acute spinalization at the
      level C6-C8 was investigated. The hypothesis was that impulse activity in vagal
      afferents has a pronounced inhibitory effect on the modulation of BK-induced PE
      by intrathecal nicotine and that spinal pathways are important in mediating this
      effect. 2. Chronic subdiaphragmatic vagotomy and elimination of vagal afferents,
      by neonatal capsaicin treatment or by application of kainic acid to the nodose
      ganglia, enhanced the potency of intrathecal nicotine depression of BK-induced
      PE, by six to seven orders of magnitude when compared with the control. 3. Acute
      subdiaphragmatic vagotomy enhanced the potency of intrathecal nicotine-induced
      depression of BK-induced PE (without changing its maximum effect), by about three
      to four orders of magnitude when compared with the sham-operated (control)
      animals (with intact vagus nerves).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7807205
TI  - Intersegmental and local interneurons in the metathorax of the stick insect
      Carausius morosus that monitor middle leg position.
AB  - 1. In the stick insect, proprioceptive information from the middle leg is used to
      define the target for the swing movement of the adjacent rear leg ("targeting
      behavior"). To investigate the underlying neural circuits, intracellular
      recordings were made in the ganglion controlling the rear leg, the metathoracic
      ganglion, while systematically moving the tarsus of the middle leg. 2. Several
      intersegmental interneurons and one local interneuron were identified as possible
      contributors to the targeting behavior. The intersegmental interneurons code the
      position of the middle leg tarsus in a highly simplified manner: test movements
      of the middle leg in the dorsal, lateral, and caudal directions from the standard
      starting position at right angles to the thorax elicit phasic-tonic responses in
      three different intersegmental neurons. The response in each interneuron actually
      reflects the movement and position at only one joint of the middle leg: for the
      neurons responding primarily to movement in the caudal, dorsal, and lateral test
      directions, the adequate stimulus is movement at the subcoxal joint, the coxa
      trochanter joint, and the femur-tibia joint, respectively. 3. The metathoracic
      local interneuron integrates information from ipsilateral middle and rear legs in
      such a way as to provide an approximate measure of the distance between the two
      tarsi in the longitudinal direction. It is depolarized in a phasic-tonic manner
      both by caudal movements of the ipsilateral middle leg and by rostral movements
      of the ipsilateral rear leg. The adequate stimulus in each case is the change in
      the angle at the subcoxal joint of the leg moved. Depolarization of this neuron
      activates retractor motoneurons, which is consistent with a role in terminating
      the swing movement. 4. Altogether the results indicate first, that the targeting
      behavior could be controlled by very few intersegmental channels and, second,
      that the nervous system encodes the position of the middle leg tarsus in terms of
      joint angles rather than in abstract, body-centered coordinates.

PMID- 7807206
TI  - Effect of longer periods of dark rearing on NMDA receptors in cat visual cortex.
AB  - 1. Cats were reared in the dark to 3, 5, and 11 mo. We studied the N-methyl-D
      aspartate (NMDA) receptor contribution to the visual response in the cortex,
      defined as the percentage reduction in visual response after application of 2
      amino-5-phosphonovaleric acid (APV). We also studied the firing rate in response
      to the optimal visual stimulus and the spontaneous activity. We made comparisons
      of all these properties between light-reared and dark-reared animals. 2. The NMDA
      receptor contribution to the visual response in layers IV, V, and VI of dark
      reared animals was substantially above that in light-reared animals at all ages
      tested. 3. The specificity of receptive field properties in dark-reared animals
      showed some degeneration between 6 wk and 3 mo of age. At > or = 3 mo, almost no
      cells were specific for orientation and direction of movement. 4. Firing rate was
      lower in dark-reared animals at all ages, suggesting a decrease in excitatory
      drive to the visual cortex. 5. Spontaneous activity was equal in dark- and light
      reared animals, suggesting that the overall level of activity (including visual
      responses as well as spontaneous activity) in light-reared animals is higher than
      in dark-reared animals. This should tend to upregulate glutamate receptors in
      general in dark-reared animals.

PMID- 7807207
TI  - Fluctuations of excitability in the monosynaptic reflex pathway to lumbar
      motoneurons in the cat.
AB  - 1. It is well known that the amplitude of successive monosynaptic reflexes (MSR),
      elicited by afferent stimuli of constant strength, fluctuate from trial to trial.
      Previous evidence suggests that such excitability fluctuations within the motor
      pool can be introduced either pre- and/or postsynaptically. Using unanesthetized
      decerebrate or decerebrate/spinal cats, we attempted to evaluate the relative
      importance of pre- and postsynaptic mechanisms to MSR variability and the
      potential contribution of changes in the identities of responding motoneurons to
      such variability. 2. Comparisons between the MSR amplitude, measured in a severed
      ventral root, and the probability of firing of up to three individual motoneurons
      in fine filaments teased from the same root, confirmed that both correlated and
      uncorrelated fluctuations of motoneuron excitability are involved in MSR
      variability. Linear regression analysis from concurrent intracellular recordings
      from homonymous motoneurons showed that the MSR fluctuations were correlated with
      the variations in membrane potential baseline, as well as with the fluctuations
      in the monosynaptic excitatory postsynaptic potential peak amplitude. In all 11
      cases tested, the former correlation was stronger than the latter. 3. Stimulation
      of the caudal cutaneous sural nerve (CCS) was used to alter the postsynaptic
      potential background on which triceps surae (GS) MSRs were generated. The
      interval chosen between CCS conditioning and the GS stimulation excluded the
      involvement of presynaptic inhibition. When conditioned by preceding CCS
      stimulation, GS population MSRs generally (8/9 cases tested) increased in
      amplitude without much change in their overall variance. However, the individual
      motoneurons that contributed to the population responses did show changes in both
      relative excitability and in the uncorrelated component of their response
      variance. About half of the concurrently recorded motoneurons (6/13) showed a
      decrease in relative excitability after CCS conditioning, 5/13 showed an
      increase, and 2/13 were unchanged. Comparison of unit and population responses
      indicated that the identities of the motoneurons that responded at any given
      level of population response were quite different with and without CCS
      conditioning. 4. High-frequency stimulation of Ia fibers was used to alter the
      state of presynaptic Group Ia-afferents that produced population MSRs. Post
      tetanic potentiation following high-frequency stimulation did not greatly alter
      the variance of population MSRs or ratio of correlated and uncorrelated
      fluctuations in MSR responses among individual motoneurons within the responding
      population. However, intratetanic depression and posttetanic potentiation of
      population MSRs were accompanied by marked shifts in individual motoneuron
      excitability relative to the population response, again indicated that changes in
      the identities of responding motoneurons contributes to population response
      fluctuations.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7807208
TI  - Activators of protein kinase C mimic serotonin-induced modulation of a voltage
      dependent potassium current in pleural sensory neurons of Aplysia.
AB  - 1. In the pleural mechanoafferent sensory neurons of Aplysia, serotonin (5-HT)
      induced spike broadening consists of at least two components: a cAMP and protein
      kinase A (PKA)-dependent, rapidly developing component and a protein kinase C
      (PKC)-dependent, slowly developing component. Voltage-clamp experiments were
      conducted to identify currents that are modulated by PKC and thus may contribute
      to the slowly developing component of 5-HT-induced spike broadening. 2. We
      compared the effects of phorbol esters, activators of PKC, on membrane currents
      with those of 5-HT. Bath application of 5-HT had complex modulatory effects on
      currents elicited by voltage-clamp pulses to potentials > 0 mV. The kinetics of
      both activation and inactivation of the membrane currents were slowed by 5-HT.
      This led to a decrease in an outward current at the beginning of the voltage
      clamp pulse and an increase at the end of the pulse. Previous work has shown that
      these effects represent, in part, the modulation of a large, voltage-dependent K+
      current (IK,V) by 5-HT. 3. Active phorbol esters mimicked some of the actions of
      5-HT on membrane currents in that they slowed activation and inactivation
      kinetics of current responses to voltage-clamp pulses more positive than 0 mV.
      This led to a decrease in an outward current at the beginning of the pulse and an
      increase at the end of the pulse. Because inactive phorbols did not mimic the
      actions of 5-HT, the effects of active phorbol esters appeared to be PKC
      specific. In addition, preexposure of the sensory neurons to active phorbol
      esters appeared to occlude the modulatory actions of 5-HT on IK,V. Thus it is
      likely that modulation of IK,V by 5-HT is mediated, at lease in part, by PKC. 4.
      To further characterize which currents were modulated by PKC, low concentrations
      of tetraethylammonium (TEA, 2 mM) were used to block Ca(2+)-activated K+ current
      (IK,Ca). Low TEA partially blocked the phorbol ester-induced increase of the
      outward current at the end of voltage-clamp pulses. These results agreed with
      previous reports that activation of PKC enhanced a fast component of IK,Ca in
      these sensory neurons. Such an enhancement would lead to an increase in outward
      current that should be blocked by low TEA. Low TEA, however, did not affect
      phorbol ester-induced decrease of the outward current at the beginning of pulse,
      where the predominant current is IK,V, which is less sensitive to TEA.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7807209
TI  - cAMP-independent effects of 8-(4-parachlorophenylthio)-cyclic AMP on spike
      duration and membrane currents in pleural sensory neurons of Aplysia.
AB  - 1. The serotonergic modulation of pleural sensory neurons in Aplysia is mediated
      via two second messenger systems: the adenosine cyclic monophosphate/protein
      kinase A (cAMP/PKA) and diacylglycerol/protein kinase C systems. Often membrane
      permeable derivatives of cAMP, such as 8-(4-parachlorophenylthio)-cAMP (pcpt
      cAMP), have been used to investigate the role of cAMP/PKA in modulating sensory
      neurons. In light of recent findings that pcpt-cAMP may have cAMP-independent
      actions, we have reexamined the effects of pcpt-cAMP on the action potential and
      membrane currents of the sensory neurons. 2. Although pcpt-cAMP (500 microM to 1
      mM) and serotonin (5-HT; 10 microM) induced comparable measures of spike
      broadening (an average increase above baseline of 29 and 40%, respectively), the
      broadening produced by the two was qualitatively different. Serotonin-induced
      broadening developed slowly over 9-12 min, was most prominent during later phases
      of the spike repolarization, and reduced the spike afterhyperpolarization. In
      contrast, pcpt-cAMP-induced broadening developed rapidly, was rather uniform
      throughout the repolarization phase of the spike, delayed the peak of the action
      potential, and increased the afterhyperpolarization. 3. Preexposure of sensory
      neurons to 5-HT did not occlude further spike broaden by subsequent application
      of pcpt-cAMP. Indeed the effects of the two were additive. In addition, the
      effects of pcpt-cAMP were not mimicked by another analogue of cAMP, 8-bromo-cAMP.
      Interestingly, most of the effects of pcpt-cAMP on the action potential were
      mimicked by 8-(4-parachlorophenyl-thio)-guanosine cyclic monophosphate (pcpt
      cGMP), but not by 8-bromo-cGMP. 4. During voltage-clamp pulses to 20 mV, pcpt
      cAMP reduced the membrane current throughout the voltage-clamp pulse, which was
      qualitatively different from the modulation of the membrane current by 5-HT. In
      addition, the pcpt-cAMP-induced reduction in the membrane current at the
      beginning of the pulse was much greater than that induced by 5-HT. Moreover,
      preexposure of sensory neurons to 5-HT did not occlude further reduction in the
      membrane current by subsequent application of pcpt-cAMP. 5. These results suggest
      that pcpt-cAMP has some mechanisms of action that are not shared by 5-HT or cAMP
      but are shared by pcpt-cGMP. In addition, these findings provide further evidence
      that results obtained with this compound should be interpreted with caution.

PMID- 7807210
TI  - Nonprimary auditory thalamic representation of acoustic change.
AB  - 1. The mismatch response, or mismatch negativity (MMN), is a neurophysiologic
      response to stimulus change. In humans and other animals, the MMN may underlie
      the ability to discriminate acoustic differences, a fundamental aspect of
      auditory perception. 2. This study investigated the role of the thalamus in the
      generation of a tone-evoked MMN in guinea pigs. Electrodes were placed in the
      caudomedial (nonprimary) and ventral (primary) subdivisions of the auditory
      thalamus (medial geniculate nucleus). Surface epidural electrodes were placed at
      the midline and over the temporal lobe. The MMN was elicited by a deviant
      stimulus (2,450-Hz tone burst) embedded in a sequence of standard stimuli (2,300
      Hz tone bursts). 3. A tone-evoked MMN was present in nonprimary thalamus but was
      absent in the primary thalamus. Surface-recorded MMNs were measured at the
      midline but not over the temporal lobe. The correspondence between nonprimary
      thalamic responses and midline surface potentials, and between primary thalamic
      responses and temporal surface potentials, is consistent with data reported for
      the auditory middle latency responses in guinea pigs. 4. The results demonstrate
      that the nonprimary auditory thalamus contributes to the generation of a tone
      evoked MMN in the guinea pig. Furthermore, the data indicate that the guinea pig
      is a feasible model for investigating central auditory processes underlying
      acoustic discrimination.

PMID- 7807211
TI  - Response variability of single cells in the dorsal lateral geniculate nucleus of
      the cat. Comparison with retinal input and effect of brain stem stimulation.
AB  - 1. We studied the degree and source of response variability in different classes
      of cell in the dorsal lateral geniculate nucleus (dLGN). The response of single
      cells to a series of contrasts of a stationary flashing light spot was measured.
      The variability analyses were based on the mean and SD of the response to a
      number of repeated stimulus presentations. The relative variability was expressed
      by the coefficient of variation (Cv; SD/mean). 2. At a given contrast, the Cv for
      lagged cells was larger than for nonlagged cells. No difference was found between
      the Cv of X and Y cells. The magnitude of the Cv was about the same as previously
      found for cells in striate cortex. Accordingly, little variability is added at
      the cortical level. The Cv decreased with increasing contrast showing that the
      reliability of response and the signal-to-noise ratio was improved with
      increasing contrast. 3. For some cells, the retinal input was determined by
      recording S potentials in addition to action potentials. The Cv of the retinal
      input was smaller than the Cv of the dLGN cells at a given contrast. Thus in the
      paralyzed and anesthetized preparation, variability was added at the geniculate
      relay. 4. The additional variability was related to modulatory input from the
      brain stem. This was shown by comparing Cv versus contrast curves for the dLGN
      cells obtained during electrical stimulation of the peribrachial region of the
      brain stem (PBR) with corresponding curves obtained without PBR stimulation.
      During PBR stimulation, which presumably mimics the effects of arousal on the
      dLGN cell, the Cv at a given contrast was reduced toward the value for the
      retinal input to the cell. Furthermore PBR stimulation increased the signal-to
      noise-ratio of the cell to the level of the retinal input. 5. When Cv was plotted
      against response rather than against contrast, approximately the same function
      was found for the various dLGN cell classes. This indicated that the variability
      basically depended on firing rate rather than on stimulus contrast. No difference
      of Cv was seen between lagged and nonlagged cells at a given level of response.
      The difference found at a given level of contrast reflected differences in firing
      rate of the two cell classes. During PBR stimulation, there was no clear
      difference between the Cvs of the dLGN cell and its retinal input at a given
      level of response.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7807212
TI  - Local intracortical connections in the cat's visual cortex: postnatal development
      and plasticity.
AB  - 1. We have studied the nature, development, and plasticity of local intracortical
      interactions by examining the visual responses from pairs of cells in the visual
      cortex of anesthetized and paralyzed adult cats and kittens at postnatal age 4
      wk. Simultaneous discharge from nearby cells was analyzed by the cross
      correlation method to infer three types of neuronal interactions: monosynaptic
      excitation, monosynaptic inhibition, and polysynaptic excitation. 2. Among cell
      pairs that exhibit correlated discharge, the nature of these interactions is
      similar in kittens and adults. For example, the mean monosynaptic delay is the
      same for cell pairs in the adult cat and the kitten: 0.8 ms. The primary
      difference in the distribution of neural interactions is the increased prevalence
      of inhibitory interactions among adult cat cell pairs compared with kitten cell
      pairs. However, in both age groups and in nearly all laminae, polysynaptic
      interactions are the most commonly observed type of interaction. 3. Neural
      interactions revealed by cross-correlation analysis also were studied with
      respect to the receptive field properties of the cells. The hierarchical theory
      proposed by Hubel and Wiesel suggests that monosynaptic excitation should be seen
      from simple to complex cells. It further suggests that complex cells do not
      provide monosynaptic excitation either to simple or to other complex cells.
      However, we find no cases of monosynaptic excitation from simple to complex cells
      in the adult cat. Moreover, we find explicitly antihierarchical connections,
      i.e., excitatory connections from complex to simple cells, in both kittens and
      adults. The excitatory influence of complex cells on simple cell receptive field
      properties is not incorporated into current models of receptive field structure
      formation. Our results suggest that complex cells might have an important
      modulatory role in simple cell discharge. 4. Plasticity of intracortical synaptic
      connections was studied by examining the dynamics of monosynaptic peaks with
      cross-correlograms. We examined Hebb's seminal hypothesis regarding synaptic
      plasticity that the excitatory connections between two neurons should strengthen
      with simultaneous activity. To test directly whether Hebbian plasticity can be
      rapidly induced by stimulus-evoked activity, the strength of monosynaptic
      excitation between pairs of neurons was monitored during periods of visual
      stimulation lasting < or = 2 h. Synaptic strength was computed by summing the
      cross-correlogram bins containing the monosynaptic peak. Transient increases in
      monosynaptic peak area are found among cell pairs linked by monosynaptic
      excitation after 8-15 min of visual stimulation. The duration and amplitude of
      these changes are similar in adult cats and kittens.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7807213
TI  - Analysis of recurrent laryngeal inspiratory discharges in relation to fast
      rhythms.
AB  - 1. Inspiratory (I) activities of recurrent laryngeal (RL) motoneurons and
      efferent nerves were studied by autospectral, interval, and coherence analyses,
      with emphasis on fast rhythms of two types: medium-frequency oscillations (MFO,
      usual range 20-50 Hz for nerve autospectral peaks) and high-frequency
      oscillations (HFO, usual range 50-100 Hz). 2. In decerebrate, paralyzed, and
      artificially ventilated cats, recordings were taken from 27 isolated single RL
      fibers (14 cats) and 8 identified RL motoneurons in the medulla (6 cats),
      together with recordings of phrenic (PHR) and RL whole-nerve activities. In
      another 50 cats, RL and PHR nerve discharges were recorded simultaneously. 3. The
      autospectra of RL units showed prominent MFO peaks with frequencies close to that
      of the RL nerve MFO spectral peak, indicating presence of this type of fast
      rhythm in the units' discharges. Spectral analysis of RL unit activity in
      different segments of the I phase showed that the frequency of a unit's MFO was
      very close to the peak (maintained) firing rate of the unit during the portion of
      I analyzed. Thus a motoneuron's MFO spectral peak reflected its rhythmic
      discharge arising from the cell's refractoriness (and possibly with the rate
      changing in the course of I). 4. The coherences of motoneurons' MFOs to nerve
      MFOs were very low or 0, indicating that correlations between unitary MFOs of the
      RL population were rare and/or weak. 5. In those cats (19/20) that had
      discernible PHR nerve HFO autospectral peaks, about half of the recorded RL
      motoneurons (16/34) had HFO. For these motoneurons, the unit-nerve HFO coherences
      were substantial, indicating widespread correlations between unitary HFOs. 6. In
      a fraction of cats, coherence peaks in the MFO frequency range were observed
      between bilateral RL nerves, and between RL and PHR nerves, at frequencies that
      were subharmonics of the HFO frequency. 7. In light of theoretical considerations
      on the generation of aggregate rhythms from superposition of unitary rhythms,
      these observations indicate that, similarly, to the case of PHR motoneurons and
      nerves. 1) RL nerve MFO arises from superposition of uncorrelated, or at most
      partially correlated, MFOs of RL units, representing the rhythmic discharges of
      the cells. It is manifested therefore as a spectral deflection with a maximum in
      the band of peak firing rates of the units. 2) RL nerve HFO arises from
      correlated, common-frequency HFOs in a subpopulation of RL units, caused by HFO
      inputs from antecedent medullary I neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7807214
TI  - Agonist and antagonist effects of nicotine on chick neuronal nicotinic receptors
      are defined by alpha and beta subunits.
AB  - 1. Functional neuronal nicotinic receptors were reconstituted in Xenopus oocytes
      by the nuclear injection of different combinations of chick and rat cDNAs
      encoding alpha and beta subunits. The pharmacology of these nicotinic receptors
      was investigated using two-electrode voltage clamp. 2. The sensitivity of the
      chick alpha 3/beta 2, alpha 3/beta 4, and alpha 4/beta 2 receptors to
      acetylcholine (ACh) and neuronal bungarotoxin differed markedly, indicating that
      both subunits contribute to the pharmacological properties of the receptors. 3.
      Nicotine acted as an agonist on the chick alpha 3/beta 4 and alpha 4/beta 2
      receptors and rat alpha 3/beta 2 receptor. In contrast, nicotine (at
      concentrations > 3 microM) was only a weak partial agonist of the chick alpha
      3/beta 2 receptor. Moreover, nicotine coapplied with 3 microM ACh on the chick
      alpha 3/beta 2 receptor acted as a potent competitive antagonist, with an IC50 of
      0.43 microM. No antagonist effect of nicotine could be revealed on the other
      nicotinic receptors. 4. The effect of nicotine was tested on hybrid receptors
      obtained by coinjection of chick and rat cDNAs encoding the alpha 3 and beta 2
      subunits (yielding the rat alpha 3/chick beta 2 and chick alpha 3/rat beta 2
      receptors). Nicotine (10 microM) strongly inhibited both hybrid receptors. 5.
      Chimeric subunits were constructed by exchanging a segment located in the
      extracellular N-termini of chick alpha 3 and alpha 4 subunits and chick alpha 3
      and rat alpha 3 subunits. These subunits were coexpressed in oocytes with chick
      or rat beta 2 subunits. The effect of nicotine on these receptors pointed to the
      importance of a 15 amino acid stretch located 3' of the first transmembrane
      segment in the determination of the agonist and antagonist action of nicotine. 6.
      Within this 15 amino acid segment, a single residue differs in chick and rat
      alpha 3 subunits, at position 198, within the ligand binding site of alpha
      subunits. Gln198 of the rat alpha 3 subunit was replaced by Thr as found in the
      chick alpha 3 subunit, using site-directed mutagenesis. The mutant subunit was
      coexpressed with the rat beta 2 subunit, yielding receptors which were inhibited
      by nicotine. 7. It is concluded that both alpha and beta subunits not only alter
      considerably the sensitivity of the nicotinic receptor to agonists and
      antagonists, but also can turn an agonist into a potent antagonist of one
      receptor subtype.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7807215
TI  - Two components of calcium currents in the soma of photoreceptors of Hermissenda.
AB  - 1. The proposed mechanism of cellular plasticity underlying classical
      conditioning of Hermissenda involves Ca2+ influx through voltage-activated
      channels. This influx triggers several molecular cascades and leads to the
      phosphorylation of K+ channels in identified photoreceptors. We studied Ca2+
      currents from isolated photoreceptors of Hermissenda with the whole cell patch
      clamp technique. Two distinct Ca2+ currents were identified in isolated
      photoreceptors on the basis of differences in their voltage dependence, kinetics,
      and pharmacology. 2. One Ca2+ current was transient (ICa(t)), with a fast onset
      (approximately 5 ms), activated at -50 mV from a holding potential of -90 mV, and
      peaked at 0 mV. The second Ca2+ current, designated as sustained (ICa(s)),
      exhibited a delayed time-to-peak, activated at -30 mV, and reached maximum at 30
      mV. 3. Steady-state activation curves for both currents were generated from
      normalized currents and fitted with the Boltzmann function; estimates of half
      activation voltages for ICa(t) were -38.8 +/- 6.7 mV (mean +/- SD; n = 9) and 3.2
      +/- 8.2 mV for ICa(s) (n = 11) with maximum slopes of 8.9 +/- 1.6 mV (n = 9) and
      11.0 +/- 2.4 mV (n = 11). 4. The inactivation of ICa(s) was slow (time constants
      > 3 s) whereas ICa(t) inactivated rapidly (time constant of inactivation at
      various voltages; 75-600 ms). 5. Ni2+ (0.8 mM), Gd3+ (0.5 mM), and amiloride (10
      microM) produced a reversible block of ICa(t) without affecting ICa(s). omega
      Conotoxin GVIA (10 nM) irreversibly blocked ICa(s) whereas nitrendipine (20
      microM) produced a reversible block. 6. ICa(t) may be responsible for steady
      state membrane potential oscillations. ICa(s) may contribute to the maintenance
      of the amplitude of the plateau phase of the generator potential.

PMID- 7807216
TI  - Brain stem integration of vocalization: role of the midbrain periaqueductal gray.
AB  - 1. The contribution of the midbrain periaqueductal gray (PAG) to the central
      regulation of vocalization was investigated by analyzing the electromyographic
      (EMG) changes in respiratory, laryngeal, and oral muscles evoked by
      microinjection of D,L-homocysteic acid (DLH) in the PAG of unanesthetized,
      precollicular decerebrate cats. Moderate to large (6-40 nmol) doses of DLH evoked
      natural-sounding vocalization as well as increases in inspiratory depth and
      respiratory rate. 2. Two basic types of vocalization were evoked, each associated
      with a distinct and characteristic pattern of respiratory, laryngeal and oral EMG
      changes. Type A vocalization (voiced sounds such as howl/mew/growl) was
      characterized by excitation of the cricothyroid (CT) and thyro-arytenoid (TA)
      muscles, and inhibition of the posterior crico-arytenoid (PCA) muscle, whereas
      type B vocalization (unvoiced hiss sounds) was characterized by excitation of the
      PCA and TA muscles and no significant activation of the CT muscle. In addition,
      stronger expiratory (external oblique, internal oblique, internal intercostal)
      EMG increases were associated with type A responses, and larger increases in
      genioglossus and digastric muscle activity were associated with type B responses.
      3. Microinjections of small doses of DLH (300 pmol-3 nmol), also evoked patterned
      changes in muscle activity (usually without audible vocalization) that, although
      of lower amplitude, were identical to those evoked by injections of moderate to
      large DLH doses. In no such experiments (175 sites) were individual muscles
      activated by small dose injections of DLH into the PAG. Further, type A
      vocalization/muscle patterns were evoked from PAG sites caudal to those at which
      type B vocalization/muscle patterns were evoked. 4. Considered together these
      results indicate: that the PAG contains topographically separable groups of
      neurons that coordinate laryngeal, respiratory, and oral muscle patterns
      characteristic of two fundamental types of vocalization and that the underlying
      PAG organization takes the form of a representation of muscle patterns, rather
      than individual muscles. 5. The patterns of EMG activity evoked by excitation of
      PAG neurons were strikingly similar to previously reported patterns of EMG
      activity characteristic of major phonatory categories in higher species,
      including humans (e.g., vowel phonation, voiceless consonant phonation). These
      findings raise the possibility that the sound production circuitry of the PAG
      could well be utilized by cortical and subcortical "language structures" to
      coordinate basic respiratory and laryngeal motor patterns that are necessary for
      speech.

PMID- 7807217
TI  - Modulatory role for the serotonergic cerebral giant cells in the feeding system
      of the snail, Lymnaea. I. Fine wire recording in the intact animal and
      pharmacology.
AB  - 1. The role of the paired serotonergic cerebral giant cells (CGCs) in the feeding
      system of Lymnaea was examined by electrophysiological and pharmacological
      techniques. 2. The firing characteristics of the CGCs were recorded by fine wires
      attached to their cell bodies in freely moving intact snails (in vivo recording)
      and their "physiological" rates of firing determined during feeding and other
      behaviors. 3. The mean CGC firing rates recorded in vivo varied between 1 and 20
      spikes/min but never reached the average rates seen in the isolated CNS (60-120
      spikes/min). Maximum rates of firing were seen during bouts of radula
      biting/rasping movements characteristic of the consummatory phase of feeding (15
      +/- 1.69 spikes/min, mean +/- SE, range 7-20 spikes/min), with lower rates seen
      during locomotion (6.7 +/- 0.75 spikes/min; range 5-9 spikes/min. The cells were
      rarely active when the animal was quiescent (1.45 +/- 0.91 spikes/min; range 0-2
      spikes/min). 4. In vivo recorded CGC firing was phase locked to the feeding
      movements of the animal, with spikes occurring just before the opening of the
      mouth, during the protraction phase of the feeding cycle. 5. Evoking firing rates
      on the CGCs in the isolated preparation similar to those seen in vivo during
      rasping movements (7-20 spikes/min) did not elicit a fictive feeding pattern in
      an inactive preparation. Neither did bath application of 10(-9) M serotonin (5
      HT; the transmitter of the CGCs). 6. To allow the modulatory role of the CGCs to
      be examined during patterned activity, the fictive feeding pattern was evoked in
      the isolated preparation by injecting depolarizing current into a modulatory
      neuron, the slow oscillator (SO). 7. The tonic firing activity of the CGCs was
      accurately maintained by current injection in the isolated preparation at rates
      equivalent to that occurring during feeding, locomotion, and quiescence in the
      intact snail. This was possible where the CGCs became silent after 1-2 h. Only
      when the CGCs activity was maintained at a rate (approximately 15 spikes/min)
      similar to that occurring during rasping, was the SO able to drive a full, high
      frequency fictive feeding pattern (15-20 cycles/min). At lower rates of CGC
      firing, the SO-driven rhythm was either of lower frequency or no rhythm occurred
      at all (CGCs silent). 8. In many isolated preparations (80%) the CGCs remained
      active, and it was difficult to maintain specific levels of tonic activity by
      current injection.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7807218
TI  - Modulatory role for the serotonergic cerebral giant cells in the feeding system
      of the snail, Lymnaea. II. Photoinactivation.
AB  - 1. Photoinactivation of dye-filled neurons was used to examine the modulatory
      role of the paired cerebral giant cells (CGCs) in the Lymnaea feeding system. 2.
      Both CGCs were filled with fluorescent dyes. Lucifer yellow was used for "soma"
      kills and injected via intracellular microelectrodes. CGC axons were retrogradely
      filled with 5 (6)-carboxyfluorescein (5-CF), through the cut ends of the ventro-
      and lateral buccal nerves, for "axonal" kills. 3. Irradiation of the CGC soma
      with a blue laser light (0.5 MW/m2) led to a loss of their recorded membrane
      potentials and the synaptic responses with their postsynaptic cells (feeding
      motor neurons). CGC coupling and axonal fluorescence were lost after axonal
      irradiation. 4. The tonic firing rate of CGC axon spikes in peripheral nerve
      roots following bilateral soma kills was reduced to approximately 15% of
      preirradiation levels (n = 2; from 52.5 +/- 3.75 spikes/min to 8.2 +/- 0.95
      spikes/min; mean +/- SE) but spike activity was not completely eliminated. 5. The
      fictive feeding rhythm was evoked by depolarizing a modulatory neuron, the slow
      oscillator (SO), before and after laser irradiation. Thirty minutes after both
      the CGCs were irradiated (n = 8), the frequency of the SO-driven feeding rhythm
      was reduced. Mean fictive feeding rates were reduced from 8.3 to 4.5 cycles/min
      for soma kills (n = 3) and from 16.2 to 9.6 cycles/min for axonal kills (n = 5; P
      < 0.05). 6. The results suggest that the CGCs play a modulatory role in
      controlling the frequency of oscillation of the feeding central pattern generator
      (CPG) in Lymnaea. The SO could still drive a full fictive feeding rhythm after
      irradiation but at a reduced rate. At least in the soma kills, the residual spike
      activity retained in the distal branches of the CGCs appeared sufficient to allow
      the SO to drive this slow rhythm.

PMID- 7807219
TI  - Cerebellar role in adaptation of the goldfish vestibuloocular reflex.
AB  - 1. The time course of eye velocity responses elicited by head velocity steps was
      compared in normal, adapted, and cerebellectomized goldfish. Vestibuloocular
      reflex (VOR) adaptation was induced by combined visual and vestibular stimulation
      that altered the ratio of eye to head velocity (VOR gain) toward values either
      higher or lower than the control amplitude. The velocity step consisted of
      alternating periods of head rotation at a constant velocity of 16 degrees/s zero
      to-peak around the vertical axis. 2. The VOR produced by head velocity steps
      consisted of an early acceleration-related component, the dynamic response,
      separated from a sustained period of constant velocity, the plateau, by a sag
      that occurred around 125-150 ms. Latency of the VOR averaged 18 ms for the
      adducting eye and 20 ms for abducting eye independent of the initial VOR gain.
      Adapted dynamic VOR responses diverged from the control records at the earliest
      detectable latency after both high and low VOR gain training. This result
      demonstrates modification in the shortest latency brain stem VOR pathway,
      presumably, the three-neuron reflex arc. 3. After acute cerebellectomy the
      adapted dynamic response was unaltered for approximately 50 ms in the low-gain
      and 70 ms in the high-gain VOR states. Not less than 30% of the altered velocity
      was retained throughout the remaining dynamic and sustained component. These
      results demonstrate that the vestibulocerebellum is not necessary for the
      maintenance of the earliest adapted eye velocity. Hence brain stem pathways are
      sufficient for the expression of the modified VOR. 4. Purkinje cells identified
      by simple and complex spikes were recorded extracellularly in the area of the
      vestibulocerebellum, where electrical stimulation produced conjugate ipsiversive
      horizontal eye movements. Independent eye and head velocity sensitivities were
      determined in response to visual world motion and VOR suppression, respectively.
      The two signals either added, canceled, or were both present in Purkinje cells
      throughout the range of eye velocity induced by vertical axis visual-vestibular
      stimulation. 5. Latency of Purkinje cell discharge to either a vestibular or
      visual velocity step exhibited means of 43 and 70 ms, respectively.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7807220
TI  - A theoretical framework for quantal analysis and its application to long-term
      potentiation.
AB  - 1. We present a new mathematical description of the complete distribution of
      electrical responses to stochastic synaptic activity (quantal analysis) that is
      intended as a model of experiments on central neuronal synapses. Unlike previous
      treatments, this distribution is calculated for each instant after the release of
      transmitter into the cleft. 2. We follow the traditional description of
      probabilistic presynaptic vesicle release. On the postsynaptic side, however, we
      assume that channel fluctuations are important and we take them into account. The
      probability of finding a given channel open after a certain amount of transmitter
      is released is calculated from detailed receptor/channel and neurotransmitter
      clearance kinetics. This approach allows us to naturally include the nonlinear
      dependence of open probability on the amount of transmitter released, with
      saturation for large transmitter doses. The distribution of open channels is
      calculated from this probability. 3. We also allow the possibility that multiple
      synaptic inputs to a target neuron may be active in a typical experiment. We have
      not treated cable effects. We explore the implications of multiple synapses for
      the nonlinearities of the system. The most important of these is that vesicles in
      different synapses have independent responses, and therefore their effects add
      linearly. 4. The resulting distributions depend heavily on what region of the
      nonlinear dose-response curve the synapses are in. Far from saturation, peaks in
      the distribution are due to vesicles, and close to saturation they are due to
      active synapses. Peak widths are due to channel fluctuations and instrumental
      noise, which we introduce to make closer contact with experiments.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7807221
TI  - Dynamics of propagating waves in the olfactory network of a terrestrial mollusk:
      an electrical and optical study.
AB  - 1. The procerebral (PC) lobe of the terrestrial mollusk Limax maximus contains a
      highly interconnected network of local olfactory interneurons that receives
      ipsilateral axonal projections from superior and inferior noses. This network
      exhibits an approximately 0.7-Hz intrinsic oscillation in its local field
      potential (LFP). 2. Intracellular recordings show that the lobe contains at least
      two classes of neurons with activity phase locked to the oscillation. Neurons in
      one class produce periodic bursts of spikes, followed by a period of
      hyperpolarization and subsequently a depolarizing afterpotential. There is a
      small but significant chance for a second burst to occur during the depolarizing
      afterpotential; this leads to a double event in the LFP. Bursting neurons
      constitute approximately 10% of the neurons in the lobe. 3. Neurons in the other
      class fire infrequently and do not produce periodic bursts of action potentials.
      However, they receive strong, periodic inhibitory input during every event in the
      LFP. These nonbursting cells constitute the major fraction of neurons in the
      lobe. There is a clear correlation between the periodic burst of action
      potentials in the bursting neurons and the hyperpolarization seen in nonbursting
      neurons. 4. Optical techniques are used to image the spatially averaged
      transmembrane potentials in preparations stained with voltage-sensitive dyes. The
      results of simultaneous optical and electrical measurements show that the major
      part of the optical signal can be interpreted as a superposition of the
      intracellular signals arising from the bursting and nonbursting neurons. 5.
      Successive images of the entire PC lobe show waves of electrical activity that
      span the width of the lobe and travel its full length along a longitudinal axis.
      The direction of propagation in the unperturbed lobe is always from the distal to
      the proximal end. The wavelength varies between preparations but is on the order
      of the length of the preparation. 6. One-dimensional images along the
      longitudinal axis of the lobe are used to construct a space-time map of the
      optical activity, from which we calculate the absolute contribution of bursting
      and nonbursting neurons to the optical signal. The contribution of the
      intracellular signals from the two cell types appears to vary systematically
      across the lobe; bursting cells dominate at middle and proximal locations, and
      nonbursting cells dominate at distal locations. 7. The direction and form of the
      waves can be perturbed either by microsurgical manipulation of the preparation or
      by chemical modulation of its synaptic and neuronal properties.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7807222
TI  - Many areas in the human brain respond to visual motion.
AB  - 1. The regions of the human brain responsive to motion were mapped using the
      H2(15)O position emission tomography (PET) activation technique and compared by
      viewing a moving random dot pattern with a stationary dot pattern. The stimulus
      was optimized in dot density and 3 degrees in diameter. 2. In addition to
      bilateral foci at the border between Brodmann areas 19 and 37, a V1/V2 focus and
      a focus in the cuneus reported earlier, we observed activations in other visual
      areas (lower BA 19 and the parieto-occipital fissure) in the cerebellum and in
      two other, presumed vestibular areas, the posterior bank of lateral sulcus and at
      the border of BA 2/40. 3. Homologies between monkey and human cortex are
      discussed.

PMID- 7807223
TI  - Testing models of the oculomotor velocity-to-position transformation.
AB  - 1. Do neural computations in premotor circuits mirror the physical properties of
      the systems they control? In 1987, Tweed and Vilis showed that oculomotor
      theories where a neural integrator converts eye angular velocity commands into
      position commands cannot be correct, because angular position is not the integral
      of angular velocity. Recently Schnabolk and Raphan proposed that an angular
      velocity integrator is nevertheless used to generate tonic commands in the
      oculomotor system. Here we test the Schnabolk-Raphan (S-R) model against Tweed
      and Vilis's quaternion (Q) model of the velocity to position transformation. 2.
      The S-R model predicts large (up to 7 degrees) transient (approximately 700 ms)
      deviations ("blips") in torsional eye position during attempted horizontal and
      vertical saccades. The Q model predicts no blips. Search coil recordings of
      saccades by 7 normal human subjects showed no large blips. 3. For approximately
      200 saccades by each subject, we plotted the area under the torsional blip versus
      the product of saccade eccentricity and magnitude. According to the S-R model,
      this graph should form a straight line with slope 1.00. According to the Q model,
      the slope should be zero. Measured slopes averaged 0.016 (range -0.073 to 0.061)
      for saccade targets at 20 degrees eccentricity and 0.040 (range 0.004-0.076) for
      targets at 40 degrees. 4. No parameter change can significantly improve the S-R
      model, but lowering one parameter eradicates the tiny inaccuracy in the Q model.
      We show that the fundamental reason for the S-R model's failure is its use of a
      commutative controller to steer a noncommutative plant.

PMID- 7807224
TI  - Administration of opiate antagonist naloxone induces recurrence of increased jaw
      muscle activities related to inflammatory irritant application to rat
      temporomandibular joint region.
AB  - 1. Our recent studies in rats have demonstrated that the small-fiber excitant and
      inflammatory irritant mustard oil injected into the temporomandibular joint (TMJ)
      region can evoke a sustained and reversible increase of electromyographic (EMG)
      activity in jaw muscles and an acute inflammatory response. The aim of the
      present study was to test if opioid mechanisms are involved in modulating the EMG
      increase evoked by mustard oil. 2. Mustard oil injected into the rat TMJ region
      evoked significant increases of jaw muscle EMG activity; the vehicle mineral oil
      had no such effect. The increased EMG activity lasted up to 20 min, and by 30 min
      after the mustard oil injection had returned to control (preinjection) levels, at
      which time administration of the opiate antagonist naloxone (1.3 mg/kg i.v.)
      induced a significant recurrence of the increase in EMG activity. This
      "rekindling" of EMG activity appeared at 5 to 10 min after the naloxone
      administration and lasted for 10 to 20 min. In contrast, naloxone administration
      in the animals receiving mineral oil injection into the TMJ region did not
      "rekindle" the EMG activity, nor did the administration of the peripherally
      acting opiate antagonist methylnaloxone or the vehicle of naloxone. 3. These
      findings reveal that the application of the opiate antagonist naloxone produces a
      recurrence of increased jaw muscle activity reflexively evoked by mustard oil
      injection into the rat TMJ region. They suggest that central opioid depressive
      mechanisms activated by the mustard oil-induced afferent barrage limit the
      duration of the evoked EMG changes.

PMID- 7807225
TI  - Neonatal whisker trimming produces greater effects in nondeprived than deprived
      thalamic barreloids.
AB  - 1. Microelectrodes and controlled stimulation of mystacial vibrissae were used to
      examine the response properties of thalamic barreloid neurons in adult rats that
      had been raised in an abnormal tactile environment produced by having one (row C)
      or four (all but C) rows of whiskers trimmed to the skin surface from birth to 45
      53 days of age. Whiskers were allowed to regrow for an average of approximately 9
      weeks before electrophysiological study. 2. Spontaneous and stimulus-evoked
      activity of single neurons in deprived barreloids was similar to that observed in
      control animals except that activity levels following stimulus offsets were
      slightly elevated. These effects were more pronounced in nondeprived barreloids.
      In addition, neurons in nondeprived barreloids responded more vigorously during
      the stimulus plateau than neurons in deprived or control barreloids. Responses to
      stimulus onsets and offsets were statistically equivalent among deprived, non
      deprived, and control barreloid neurons. 3. The findings indicate that increased
      spontaneous and stimulus-evoked activities observed previously in deprived
      cortical barrels reflect abnormalities within the cortex itself. Previously
      observed increases in neuronal activity in nondeprived cortical barrels probably
      reflect abnormalities in the input signals they receive from nondeprived
      barreloids as well as possible changes in cortical circuitry. Effects in the
      thalamus may be due to abnormal lateral inhibitory interactions between inputs
      from previously trimmed and nontrimmed whiskers.

PMID- 7807226
TI  - Presynaptic enhancement of excitatory synaptic transmission by beta-adrenergic
      receptor activation.
AB  - 1. Previous studies have shown that beta-adrenergic receptor activation has many
      effects on neuronal function in hippocampal area CA1. However, all of the
      physiological effects of beta-adrenergic receptor activation in this region
      reported to date have been attributed to postsynaptic mechanisms. A series of
      studies was performed to test the hypothesis that beta-adrenergic receptor
      activation also acts presynaptically to enhance excitatory synaptic transmission.
      2. Application of the selective beta-adrenergic agonist isoproterenol to
      hippocampal slices induced an increase in the amplitude of evoked excitatory
      postsynaptic currents (EPSCs) in CA1 pyramidal cells. This response was
      potentiated in the presence of a cyclic nucleotide phosphodiesterase inhibitor.
      Isoproterenol also resulted in the appearance of a late inward synaptic current
      that likely represents polysynaptically evoked EPSCs. Both the increased
      amplitude of the monosynaptic EPSC and the appearance of polysynaptic EPSCs in
      response to isoproterenol were blocked by H89, an inhibitor of adenosine 3',5'
      cyclic monophosphate (cAMP)-dependent protein kinase. 3. Isoproterenol induced an
      increase in the frequency of spontaneous miniature EPSCs but did not affect the
      amplitude of these currents. In addition, isoproterenol had no effect on currents
      elicited by direct application of the ionotropic glutamate receptor agonist,
      (R,S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA). 4. These
      results suggest that activation of presynaptic beta-adrenergic receptors enhances
      synaptic transmission in area CA1 via activation of cAMP-dependent protein
      kinase.

PMID- 7807227
TI  - The cerebellar nodulus and ventral uvula control the torsional vestibulo-ocular
      reflex.
AB  - 1. The vestibulo-ocular reflex (VOR) was investigated in rhesus monkeys before
      and after surgical ablation of the cerebellar nodulus and ventral uvula. The
      lesion resulted in an alteration of the torsional VOR: compensatory eye movements
      were poor in the low frequency range and the time constant was reduced to values
      comparable to those of primary semicircular canal afferents. In addition, animals
      permanently lost their ability to generate torsional optokinetic nystagmus (OKN).
      2. The effects of the lesion on the torsional VOR differed from those observed in
      the horizontal and vertical vestibulo-ocular systems. While the vertical VOR and
      OKN were unaltered, the horizontal VOR and OKN were characterized by increased
      time constants and smaller phase leads during low frequency head oscillations. 3.
      These results suggest that the cerebellar nodulus and/or ventral uvula exert a
      distinct and specific dynamic control on the torsional vestibulo-ocular and
      optokinetic reflexes. Such specific effects on the torsional system could reflect
      a functional segregation of the vestibulo-cerebellum in terms of the controls of
      torsional versus horizontal and vertical slow phase eye movements.

PMID- 7807228
TI  - Wide-field nondirectional visual units in the pretectum: do they suppress ocular
      following of saccade-induced visual stimulation.
AB  - 1. Direction-selective neurons in the nucleus of the optic tract (NOT) provide
      motion signals for controlling ocular following responses. When stimulated at low
      temporal and high spatial frequencies of motion (slow speeds), these retinal-slip
      neurons produce directional responses. When stimulated by motion at high temporal
      and low spatial frequencies (the visual conditions during saccades) the
      spontaneous activities of the neurons are inhibited by motion in all directions.
      A second class of neurons in, or near, the NOT have large receptive fields, are
      nondirectional, and are tuned to detect the same spatial and temporal stimuli
      that induce nondirectional inhibition in the retinal-slip neurons. We suggest
      that the nondirectional cells provide an inhibitory input for the retinal-slip
      neurons and therefore prevent ocular following of the visual displacements that
      accompany saccades.

PMID- 7807229
TI  - A story with no happy ending.

PMID- 7807230
TI  - Perceptions of nursing staff development. A replication study.
AB  - The authors, in this study, replicate the research of Kirsch (1987, 1990) and
      contribute to the knowledge base of nursing staff development. This replication
      partially supports the original research findings related to work satisfaction,
      organizational commitment, hospital-sponsored education, and intent to remain in
      the institution. An extension of the replication study was the comparison of
      responses from full and part-time nursing staff members.

PMID- 7807231
TI  - Needs assessment for a patient education program in a nursing department. A
      Delphi approach.
AB  - Nursing staff members reported patient education activities in a teaching
      hospital during a needs assessment conducted as a three-round modified Delphi
      study. Members of the clinical practice committee and nursing staff members from
      all patient units were surveyed during three consecutive rounds. Results include
      the characteristics and priorities of nursing staff members' current
      interventions related to patient education. Programmatic directions for the
      nursing service organization, including the development of inservice education
      programs for creating a formal teaching plan, were identified.

PMID- 7807232
TI  - Planning an agency-wide inservice.
AB  - From planning an inservice program on a relatively simple change to presenting a
      number of changes together, the challenge for nursing staff development
      specialists is to provide high-quality programs in an efficient and effective
      manner to achieve identified outcomes. In this article, the author reviews
      considerations in the formative stages of a hospital-wide inservice program, with
      a focus on planning to achieve quality, efficiency and effectiveness, and
      measurable outcomes.

PMID- 7807233
TI  - Staff nurse leadership and professional growth in the mentor role.
AB  - Nurses frequently commit only for a short term to medical/surgical nursing to
      pursue opportunities in more specialized areas. The implementation of a
      mentorship program for orientation incorporates professional role development and
      leadership opportunities for the staff nurse serving in the mentor role. The
      mentorship has resulted in a mutually beneficial mentor-orientee relationship.
      Practical triumphs for a successful mentorship as well as ongoing challenges are
      identified.

PMID- 7807234
TI  - Hospital-patient education. Current status and future trends.
AB  - With the increasing number of older patients and the decreased length of hospital
      stays, nurses are faced with the challenge of ensuring that the patient or
      caregiver can manage care after discharge. Patient education facilitates the
      maintenance and promotion of self-care behaviors. Health-care trends, educational
      materials, costs and reimbursements, and innovative methods for education all
      affect the future of hospital-based patient education.

PMID- 7807235
TI  - Nurses' views on preceptorship programs and preceptor and preceptee experiences.
AB  - As part of developing an Army Nurse Corps Preceptorship Program, a survey queried
      70 Army Nurse Corps officers about preceptorship program content and process.
      Respondents provided information about personal, interpersonal, clinical, and
      environmental characteristics of preceptorships. The most important preceptor
      characteristic was clinical competence. Recommended program length was at least 6
      weeks. Transition to clinical practice was a key objective of preceptees.

PMID- 7807236
TI  - Enhancing staff skill. Developing critical pathways at a community hospital.
AB  - Clinical pathways are an essential tool in implementing case management. The
      authors, in this article, describe how one institution developed and implemented
      critical pathways. The result was enhanced staff skill in physical assessment,
      patient/family teaching, and communication with physicians.

PMID- 7807238
TI  - Mandatory inservice programs using self-learning modules.

PMID- 7807237
TI  - Health care reform: implications for competencies in staff development and
      continuing education.

PMID- 7807239
TI  - The sixty second nurse.

PMID- 7807240
TI  - How staff development specialists can promote and facilitate research.

PMID- 7807241
TI  - Curriculum design in nursing staff development.
AB  - Curriculum design can be used as a blueprint for the activities of a nursing
      staff development department. In this article, the author provides an overview of
      the major elements of curriculum design and their use in the service setting. The
      American Nurses Association Standards for Nursing Staff Development are
      incorporated into the curriculum elements of philosophy, conceptual framework,
      goals and objectives, content organization, instructional design, and evaluation.

PMID- 7807242
TI  - Collaborative teaching--learning: a potential framework for staff development
      educators.
AB  - The nursing staff development educator is challenged constantly to use adult
      education principles when planning programs and evaluating outcomes. The
      educator, however, may lack a formal theoretical framework to accomplish this
      goal. In this study, the author suggests that the principles of collaborative
      teaching-learning may serve as a framework to promote both program development
      and staff competency within the hospital setting.

PMID- 7807243
TI  - From theory to practice ... a career ladder that works.
AB  - Frustrated with an increasing turnover rate and role ambiguity, nursing leaders
      at The University Hospitals sought to implement a program to enhance recruitment
      and retention efforts. Nursing administration members thought that a career
      ladder would foster continued development of the novice as well as the expert
      practitioner. The collaborative efforts of representatives from The University
      Hospitals, which is made up of Oklahoma Memorial Hospital, Children's Hospital of
      Oklahoma, and O'Donoghue Rehabilitation Institute, resulted in an eight-tier,
      four-track career ladder. After 2 years, The University Hospitals Career Ladder
      continues to be an effective tool for recruiting and retaining nurses.

PMID- 7807244
TI  - Effect of a teaching plan on a nursing staff's knowledge of pressure ulcer risk,
      assessment, and treatment.
AB  - The authors, with this research, measure the effects of a teaching intervention,
      including information on risks, assessment, and treatment of pressure ulcers, on
      hospital nursing staff member's knowledge scores. The 100-item, true-false test
      had content validity, because items were based on current pressure ulcer
      literature. Five experts judged the test for accuracy, and two experts evaluated
      the congruence of the teaching intervention and test. Forty-eight subjects
      completed the experimental condition; 54 completed the control condition. The
      teaching intervention had a significant effect on knowledge scores.

PMID- 7807246
TI  - Critical care education. A consortium approach.
AB  - Staff development specialists are being forced to look at more economical models
      to present traditional educational programs. In this article, the author
      describes a creative approach taken by a nurse educators' consortium in northern
      New Jersey to collaboratively organize and present a basic critical care course.
      Benefits to learners as well as educators are identified. Cost analysis of this
      program versus that of a more traditional approach demonstrates the savings for
      each of the participating hospitals.

PMID- 7807245
TI  - Staff development sessions. A strategy to facilitate nursing staff education with
      limited teaching resources.
AB  - A reduction in clinical nursing educator positions resulted in the need for the
      Department of Nursing to continue to facilitate the professional development of
      nursing staff members with limited resources. In this article, the author
      describes a program, developed by the central Nursing Education Department at The
      Toronto Hospital, that was offered to clinical resource nurses, nurse managers,
      patient care coordinators, and preceptors. These individuals could use the
      information to promote the development of nursing staff members at the unit
      level. Several topics were presented: self-directed learning, needs assessment,
      behavioral objectives, lesson plans, teaching strategies, educational program
      evaluation, and clinical evaluation. Program evaluations were positive, and 45%
      of the respondents indicated they had the opportunity to apply what they learned.

PMID- 7807247
TI  - The '93 update: a newsletter to meet mandatory education requirements.

PMID- 7807248
TI  - Health promotion and patient teaching.

PMID- 7807249
TI  - A literature review of competency-based orientation for nurses.
AB  - This article is a literature review of competency-based orientation (CBO), which
      includes a description of the component parts of CBO, its efficiency and
      effectiveness, and a discussion of how various hospitals have implemented CBO.
      Suggestions for approaching the design of CBO may help staff development
      educators make a decision to change to CBO.

PMID- 7807251
TI  - Preceptor development. Use a staff development specialist.
AB  - Preceptor orientation is a well identified need. Less often identified is the
      critical role the staff development specialist plays in the ongoing support and
      development of preceptors. In this article, the authors explain activities of
      coaching, facilitating, mentoring, and consulting. These role components are
      essential in the ongoing development of preceptors. This support also may help
      retain preceptors.

PMID- 7807250
TI  - Partners in nursing education.
AB  - In this article, the authors present the efforts of several hospitals in a large
      southern city to collaborate on continuing education projects to meet the needs
      of the nursing staff. In 1985, four hospitals formed a health maintenance
      organization. An outgrowth was the formation of a critical care consortium whose
      main objective was to develop an entry level critical care course. The authors
      discuss the development of this course, the advantages and disadvantages of a
      partnership, and the results of 7 years of experience.

PMID- 7807252
TI  - Evaluating the impact of a continuing education program on change in gerontologic
      nursing practice.
AB  - In this article, the authors describe behavior changes reported by nurses after
      attending a continuing education program that addressed nursing care of the
      gerontologic client in the acute hospital setting. Although participants
      reflected positively upon knowledge gained at the conference and described
      themselves as amenable to change, they associated environmental and
      administrative factors negatively with implementation of practice changes.
      Conclusions from descriptive analysis of responses yielded suggestions for
      strategies to enhance the impact of continuing education programs on nursing care
      of the aged client.

PMID- 7807253
TI  - Novice critical care nurses' affective responses to orientation.
AB  - To provide the best possible learning experience for orientees, staff development
      educators must be aware of the affective responses of orientees to the
      orientation period. In this article, the authors use an adult education framework
      to describe a research study of these responses, and they make suggestions for
      the application of the results.

PMID- 7807254
TI  - Recertification in cardiopulmonary resuscitation. A comparison of two teaching
      methods.
AB  - In this study, the authors compare knowledge scores, pass/fail rate, time spent,
      satisfaction, and skill retention between two teaching methods used in
      cardiopulmonary resuscitation (CPR) recertification. Seventy subjects were
      assigned randomly to either traditional or computer method of instruction.
      Knowledge was evaluated by written examination. Psychomotor skills were evaluated
      either by a Basic Cardiac Life Support certified instructor (control group) or
      the computer (experimental group) and reevaluated by an instructor at a 6-month
      interval. There was no significant difference between the groups in knowledge or
      performance scores. However, significant differences in time spent, learner
      satisfaction, and pass/fail rate all favored the traditional method of
      instruction. These findings conflict with the results of prior studies on the use
      of the computer interactive learning system.

PMID- 7807255
TI  - Development of a comprehensive examination to evaluate licensed practical nurses'
      cognitive knowledge of intravenous therapy administration.
AB  - In this article, the authors describe the systematic and collaborative processes
      used by a group of nursing educators to develop a comprehensive exam to evaluate
      licensed practical nurses' cognitive knowledge of intravenous therapy practice.
      The examination was written to meet the new requirements mandated by the State of
      Florida Board of Nursing related to the expanded role of the licensed practical
      nurse. After statistical analysis and test revision, the examination would
      eventually be a challenge examination for those licensed practical nurses who had
      acquired this knowledge previously.

PMID- 7807256
TI  - Open house for nursing programs: keeping faculty in touch.

PMID- 7807257
TI  - Is your department manual user friendly?

PMID- 7807258
TI  - Occupational cancer among women: a conference overview.

PMID- 7807259
TI  - Proceedings of an International Conference on Women's Health: Occupation and
      Cancer. Baltimore, Maryland, November 1993.

PMID- 7807260
TI  - Where women work and the hazards they may face on the job.
AB  - This article discusses historical and social reasons for the emergence of women's
      occupational cancer as a current area of research interest. It develops
      background information on relationships between social and occupational factors
      that must be considered if research on women, work, and cancer is to be well
      designed. These factors include specific occupational titles and tasks and the
      socioeconomic status and roles of women being studied. In addition, detailed
      demographic data on the industrial and occupational distribution of female
      workers are provided as one basis for setting priorities for women's occupational
      cancer studies. These demographic data are supplemented by analysis of specific
      potential exposures to carcinogens and other hazardous substances. By comparing
      lists of known and suspected carcinogens published by the International Agency
      for Research on Cancer to the industries and uses listed by the Hazardous
      Substances Data Base of the National Library of Medicine, a new target list of
      industries of significance to female workers was derived. Its implications are
      discussed herein.

PMID- 7807261
TI  - A historical perspective of some occupationally related diseases of women.
AB  - The study of occupational diseases among women has been minimal, and when
      observations of adverse health effects have been made, they often have been
      obscured, ignored, or mismanaged. Occupational exposures of women to beryllium,
      benzene, and vinyl chloride serve as past examples of indifference to the plight
      of women in the workplace. The lack of regulation for waste anesthetic gases and
      antineoplastic drugs to protect health care workers and veterinarians indicates
      that this indifference continues today.

PMID- 7807262
TI  - Recent cancer patterns among men and women in the United States: clues for
      occupational research.
AB  - Investigation of cancer rates--including trends over time, geographic variations,
      and differences by race, gender, and age--may identify patterns suggesting
      environmental exposures of potential occupational origin. National mortality data
      spanning the 40-year period from 1950 to 1989 were used to assess the patterns of
      several cancers for which occupational components have been identified among men,
      including cancers of the lung and bladder, non-Hodgkin's lymphoma, and leukemia,
      and for cancers of particular concern to women, such as breast and ovarian
      cancer, but for which occupational factors have not been well characterized.
      Newly available preliminary data show substantial geographic variation in cancer
      mortality rates at the county level during the 1970s and 1980s. Future analyses
      of the patterns, correlations with industrial indicators, and analytic studies
      should be fruitful in identifying occupational and other risk factors for cancers
      among women.

PMID- 7807263
TI  - Inclusion of women and minorities in occupational cancer epidemiologic research.
AB  - A survey of published epidemiologic studies from eight journals during 1971 to
      1990 was conducted to assess the proportion and characteristics of occupational
      cancer studies that have included women and minorities. A total of 1233 reports
      included 562 (46%) with subjects limited to white men. The remaining 671 (54%)
      had subjects from other race-gender groups. Thirty-five percent included white
      women, but only 14% presented any analyses of white women specifically and only
      7% presented more than five risk estimates. The proportions with analyses of
      nonwhite women (any = 2%; detailed = 1%) or men (any = 7%; detailed = 3%) were
      also small. Studies with detailed analyses of women and minorities tended to use
      weaker methodologies (ie, proportionate mortality or cross-sectional design) than
      the studies of white men and were less able to provide convincing data on the
      occupational cancer risks of women and minorities.

PMID- 7807264
TI  - Setting occupational health standards: toxicokinetic differences among and
      between men and women.
AB  - Differences between and among men, nonpregnant women, and pregnant women can
      influence exposure and response to workplace toxicants. These differences should
      be delineated, compared, and used when setting regulatory standards to protect
      workers from potentially hazardous workplace environments. Anatomical and
      physiological parameters include: body composition; surface area; blood, organ,
      and tissue volume; metabolism; and cardiovascular, pulmonary, gastrointestinal,
      and renal structure and function. Although men differ among themselves, on
      average, they also differ from women by weighing more, being taller, and having a
      larger surface area. Total body water is 40% greater in men than nonpregnant
      women; however, during pregnancy, body water increases from 29 to 33 liters.
      Extracellular and intracellular water volumes are smallest in nonpregnant women,
      increase with pregnancy, but remain smaller than those in men. Pulmonary function
      differs; pregnant women have the largest minute volume and greatest volume of air
      exchanged in an 8-hour period. This article compares anatomical, physiological,
      and toxicokinetic characteristics of men and nonpregnant and pregnant women to
      explore how differences in these factors contribute to variations in exposures,
      target tissue doses, and responses to workplace or environmental chemicals.

PMID- 7807265
TI  - Gender differences in animal bioassays for carcinogenicity.
AB  - Animal bioassays for carcinogenicity are essential components of occupational
      health studies. Animal data that have been collected under controlled
      experimental conditions provide definitive information about the carcinogenic
      activities of individual substances or defined mixtures and their relative
      potencies in the test species. Such information serves as a frame of reference
      for clinical and epidemiologic studies, pointing to potential adverse health
      effects and to the types of substances that might produce them. This article
      alerts the occupational and environmental health communities to 20 substances
      that produced breast tumors, 13 substances that produced uterine tumors, and 8
      substances that produced ovarian tumors in long-term National Toxicology Program
      animal studies. Each of the substances also produced neoplasms at other body
      sites. Follow-up studies of molecular measures of exposure and response in people
      and in animals will reduce the uncertainties of transspecies extrapolations.

PMID- 7807266
TI  - Cancer mortality patterns among female and male workers employed in a cable
      manufacturing plant during World War II.
AB  - A cohort mortality study was conducted among 9028 (3042 women, 5986 men) workers
      potentially exposed to chlorinated naphthalenes (chloracnegens structurally
      similar to dioxins) and asbestos in the manufacture of Navy cable during World
      War II. Based on mortality through December 31, 1985, standardized mortality
      ratios (SMRs) for all cancers was 1.03 in women (95% confidence interval [CI] =
      0.9 to 1.17) and 1.18 in men (95% CI = 1.10 to 1.26). There were no significant
      elevations in causes of death hypothesized a prior to be associated with
      chlorinated naphthalene exposure (malignant neoplasms [MN] of connective tissue,
      liver, and lymphatic and hematopoietic organs). An excess of MN of the connective
      tissue was suggested for workers with over 1 year of exposure and 25 years of
      latency (SMR = 3.54; 95% CI = 0.97 to 9.07). Among cancer sites not hypothesized
      to be related a priori, three showed concordant excesses among both genders (MN
      of stomach; rectum; and trachea, bronchus, and lung). No significant elevations
      occurred in hormonally related cancers among women. Cancer mortality among 460
      individuals with chloracne (431 men, 29 women) was similar to that of the entire
      cohort, although the chloracne subcohort showed significant excesses in two rare
      causes of death (MN of esophagus, SMR = 3.26; "benign and unspecified neoplasms,"
      SMR = 4.93). Use of county referent rates decreased SMRs for stomach, rectal, and
      buccal cavity cancer, suggesting a role for nonoccupational risk factors. It is
      difficult to draw conclusions about carcinogenicity of chlorinated naphthalenes
      because of study limitations, most importantly, concomitant asbestos exposure and
      the relatively short duration of exposure to chlorinated naphthalenes among most
      of the cohort.

PMID- 7807267
TI  - Cancer mortality in female and male dry-cleaning workers.
AB  - A cohort study of dry-cleaning workers (1109 women, 592 men) in the mid-1980s
      revealed significant excess bladder cancer mortality. This article updates vital
      status through 1990. Significant excesses were seen for bladder cancer (nine
      deaths, standardized mortality ratio [SMR] = 2.54, 95% confidence interval [CI] =
      1.16-4.82), esophageal cancer (10 deaths, SMR = 2.14, 95% CI = 1.02-3.94), and
      intestinal cancer (26 deaths, SMR = 1.56, 95% CI = 1.02-2.29). In a subcohort
      exposed only to perchloroethylene (PCE), those with 5 or more years of employment
      and 20 or more years since first exposure had a significant increased risk of
      esophageal cancer (four deaths, SMR = 7.17, 95% CI = 1.92-19.82). Women had
      significant excess esophageal cancer (five deaths, SMR = 3.24, 95% CI = 1.05
      7.58) and elevated SMRs for intestinal, pancreatic, and bladder cancer mortality.
      This study confirms the esophageal cancer risk among dry-cleaning workers seen in
      another study and suggests an association with PCE. It further documents the
      risks for intestinal, pancreatic, and bladder cancers in this industry.

PMID- 7807268
TI  - Gender differences in hematopoietic and lymphoproliferative disorders and other
      cancer risks by major occupational group among workers exposed to benzene in
      China.
AB  - Gender differences in risk for leukemia and other selected and combined disease
      categories were examined by major occupational category for 74,828 benzene
      exposed workers compared to 35,805 unexposed workers from 12 cities in China. No
      significant differences in the relative risks for total mortality and cancer
      mortality were found between female and male benzene-exposed workers, although
      risks tended to be somewhat higher among male than among female employees. Both
      female and male workers in several occupational categories had notably increased
      risks for all hematopoietic and lymphoproliferative (HLP) malignant and
      nonmalignant disorders combined and for total leukemia. Variation in risk for HLP
      disorders by occupational category was observed in both genders, with highest
      risks for male and female chemical manufacturing workers, female nonproduction
      employees, and male printers. However, the numbers of leukemia and other HLP
      malignancies in each category were small. The findings suggest that both female
      and male benzene-exposed workers in several occupational categories experience
      excess leukemia and other HLP disorders with relatively minor gender differences.
      Although this population is one of the largest cohorts of benzene-exposed workers
      studied to date, evaluation of the observed variation in risk for HLP neoplasms
      among the occupational groups for workers of each gender is limited by the small
      numbers of these relatively rare malignancies.

PMID- 7807269
TI  - Mortality patterns among female and male chrysotile asbestos textile workers.
AB  - This study updates a retrospective cohort mortality analysis of workers from a
      South Carolina textile plant where chrysotile asbestos was the primary exposure.
      The update adds 15 years of observation to the original study, adds analyses of
      white women and black men, and allows comparison of mortality risks between
      race/gender groups. The total cohort includes 3,022 workers: 1,229 white women
      (363 deaths), 1,247 white men (607 deaths), and 546 black men (289 deaths).
      Statistically significant risks for lung cancer were observed among white women
      (standardized mortality ratio [SMR] = 2.07; 90% confidence interval [CI] = 1.55
      2.71) and white men (SMR = 2.24; 90% CI = 1.83-2.72); both of these groups
      exhibited positive exposure-response trends. Although the lung cancer risk among
      black men was lower than expected (SMR = 0.70; 90% CI = 0.42-1.08), a
      statistically significant increase was observed at high levels of exposure.
      Statistically significant excess risk for pneumoconiosis and other respiratory
      diseases were observed for all race/gender groups. Despite the relatively high
      percentage of white women lost to follow-up and missing death certificates, both
      of which allow underestimation of the true relative risk, statistically
      significant excess risks were observed for lung cancer and pneumoconiosis among
      this group.

PMID- 7807270
TI  - Mortality rates in a female cohort following asbestos exposure in Germany.
AB  - A cohort study was conducted of 616 German female workers with a history of
      exposure to asbestos. Standardized proportionate mortality analysis was done
      except for mesothelioma, for which proportionate mortality was computed based on
      best evident cause of death. Mortality from lung cancer was increased three times
      over expected value. Death rates due to mesothelioma were 340 times higher than
      in the general population. Female mortality rates surpassed those observed in men
      twofold for lung cancer and fourfold for mesothelioma. In comparison with
      published data from international cohort studies, the observed mortality for
      mesothelioma in our female cohort appeared higher than that previously reported.
      German women with a history of asbestos exposure are considered a high-risk group
      for developing mesothelioma and lung cancer. They should be a target group for
      intervention strategies (eg, chemoprevention, smoking cessation, early cancer
      detection).

PMID- 7807271
TI  - Lung cancer mortality among female mine workers exposed to silica.
AB  - A mortality cohort study (1951-1988) was conducted on 526 female workers in two
      lead and zinc mines in southwestern Sardinia (Italy), 310 of whom had been
      exposed to silica. Women exposed to silica showed a nonsignificant 38% increase
      in the standardized mortality ratio (SMR) for nonmalignant respiratory diseases,
      which was highest and statistically significant among women at the mine with the
      highest exposure to silica (SMR = 217; 95% confidence interval [CI] = 104, 400;
      based on 10 observed and 4.6 expected deaths). Five deaths from lung cancer also
      occurred among those exposed to silica (SMR = 283; 95% CI = 91,660), but the
      excess was not related to the level or duration of exposure. No information was
      available concerning lifestyle risk factors in this cohort. However, smoking was
      quite rare among Sardinian women at the time cohort members worked, so it may be
      presumed that very few of them were smokers.

PMID- 7807272
TI  - Statistical power to detect occupationally related respiratory cancer risk in a
      cohort of female employees in the US man-made vitreous fiber industry.
AB  - The current update of the US man-made vitreous fiber production worker cohort
      includes women for the first time. Preliminary comparisons of 3,820 female and
      27,767 male workers from 11 participating fibrous glass plants show different
      hiring patterns during World War II. The gender-specific person-year
      distributions are similar with respect to duration of employment and time since
      first employment. The current follow-up of 118,559 person-years for women
      provides an estimated 80% power to detect a threefold relative risk of
      respiratory cancer for women who worked more than 14 years in these plants, based
      on a Poisson regression analysis of the cohort rates. When women comprise a small
      fraction of the cohort, the statistical power may be inadequate to detect risks
      of the magnitude typically of interest in studies of men.

PMID- 7807273
TI  - High-risk occupations for women exposed to cadmium.
AB  - Occupational exposures to cadmium are associated with increased risk of lung
      cancer and renal disease. The Occupational Safety and Health Administration
      (OSHA) published two standards for cadmium on September 14, 1992 that reduced the
      permissible occupational exposure limit. In the cadmium industry, women were less
      likely to be exposed to high levels of cadmium and more likely to hold job titles
      containing the word "hand" than were men. Only small numbers of female workers
      were exposed to any level of cadmium. OSHA's risk assessment relied, in part, on
      morbidity and mortality data from male workers and in part on rodent (animal)
      data from both sexes. OSHA did not evaluate illness rates specific to female
      workers. Several factors may alter the risk of these illnesses and their sequelae
      among workers, including differences in smoking, route of exposures, ability to
      wear personal protective equipment, and lifestyle.

PMID- 7807274
TI  - Exposure assessment and gender differences.
AB  - Exposure assessments for occupational epidemiological studies are typically
      conducted to (1) establish risk gradients with exposure, evaluating a potential
      causal relationship, or (2) estimate exposure-response dosimetry for quantitative
      risk calculations. Unavailable quantitative exposure data require use of
      surrogate or qualitative measures. Differences in women's employment patterns may
      make surrogate measures less reliable, resulting in systematic errors. Exposures
      associated with traditionally female careers have not been fully evaluated.
      Occupational cohorts are often defined to include workers with a minimum
      employment duration or employment for some minimum time in exposure-related jobs,
      thereby excluding many women workers. Even when included among studied and
      exposed worker cohorts, women's domestic exposures may confound risk evaluation.
      Male/female differences in xenobiotic uptake, distribution, kinetics, and
      metabolism may affect the relationship between external exposure and resulting
      biologically effective dose. Clinical factors alter the recognition of disease
      among women workers, confounding risk determination. Recognizing these problems
      during design and analysis of occupational cancer epidemiology research is
      essential to develop valid preventive strategies.

PMID- 7807275
TI  - Evaluation of exposure data from men and women with the same job title.
AB  - In the epidemiological approach to occupational cancers, large bodies of data
      must be analyzed to find rare cases of cancer. The exposure status of workers
      must therefore be assessed. Inaccuracies will lead to bias toward the null value
      in certain cases. Job title has often been used as a proxy for exposure status.
      This study was undertaken to examine content (ie, tasks and activities)
      associated with job title among men and women in a large Quebec municipality.
      Occupational accident reports were studied for 1589 accidents, and 113 men and
      women workers were interviewed about job content. Women and men did not seem to
      have the same accident rates. From interview data, it appeared that women and men
      with the same job title did not perform the same tasks. Thus, they might have
      different exposures. The data reported here support caution in using job title to
      estimate exposure for both genders if the job-exposure matrix has not previously
      been validated separately by gender. In addition, it may be unwise to adjust
      relationships between job title and cancer incidence for gender, thus treating
      gender as a confounder when it may be a proxy for specific exposures.

PMID- 7807276
TI  - Women in the formaldehyde industry: their exposures and their jobs.
AB  - Several studies have examined disease risks for women separately from risks for
      men, but few have examined exposure differences. This report used data from an
      epidemiological study of formaldehyde workers to compare formaldehyde exposures
      between men and women. Exposures were estimated from historical monitoring
      results, walk-through workplace surveys, interviews with long-term workers, and
      reviews of historical records. The mean of the exposures in the first job, the
      last job, and the highest exposed job were calculated by gender. Differences were
      found when all subjects were included in the analysis (men having higher
      exposures, on average, than women), but when nonexposed subjects were removed
      (40% of women, 6% of men), differences were minor. There was a substantial
      difference in the estimated peak exposure between men and women that decreased,
      but remained, when only exposed subjects were included. Evaluation of exposures
      in 1940 to 1945, 1965, and 1979 found that women had a higher average exposure
      than men in 1940 to 1945, but this pattern was reversed in 1965. By 1979, the
      average difference between the two genders had disappeared. A comparison of
      cumulative exposure found that exposed women had half the total exposure of
      exposed men. More men than women were exposed to other chemicals. Women tended to
      predominate in clerical, laboratory, assembly, finishing, inspecting, packing,
      and shipping jobs.

PMID- 7807277
TI  - Occupation and ovarian cancer: a case-control study in the Washington, DC,
      metropolitan area, 1978-1981.
AB  - Ovarian cancer risk factors may be genetic, reproductive, or hormonal in nature.
      Occupational exposure to talc and other carcinogenic substances has not been
      studied in relation to ovarian cancer risk. We therefore examined the job
      histories of 296 women aged 20 to 79 who were diagnosed with epithelial ovarian
      cancer in the Washington, DC area in 1978 to 1981, comparing them to 343 hospital
      controls, matched for age and race. A blind exposure assessment, evaluating each
      job/industry combination for potential exposure to talc, ionizing radiation,
      polycyclic aromatic hydrocarbons, and solvents was conducted by an industrial
      hygienist blind to case-control status. Women exposed to talc had a relative risk
      of ovarian cancer below the null, but the confidence interval was wide and there
      was no evidence of a trend. Women exposed to polycyclic aromatic hydrocarbons had
      an elevated relative risk, also with a wide confidence interval and no evidence
      of a trend with duration.

PMID- 7807278
TI  - beta 2-GPI-dependent and independent binding of anticardiolipin antibodies in
      patients with recurrent spontaneous abortions.
AB  - We measured anticardiolipin antibodies (aCL) in plasma samples from 214 women
      with a history of recurrent spontaneous abortions by an enzyme-linked
      immunosorbent assay (ELISA) utilizing solid phase cardiolipin (CL) and beta 2
      glycoprotein I (beta 2-GPI). Sixteen patients (7.5%) were positive for beta 2-GPI
      dependent aCL. Though beta 2-GPI appeared to enhance the binding of aCL, beta 2
      GPI-independent aCL were also observed in these patients (4.7%). The patients
      were classified into three groups on the basis of their medical history, and
      analysis of data of individual groups revealed that the incidence of beta 2-GPI
      dependent aCL was significantly higher in patients who had experienced at least
      one fetal loss in the second or third trimester.

PMID- 7807279
TI  - Reactivity of chagasic sera with crude and highly purified glycosphingolipid
      fractions from Trypanosoma cruzi epimastigotes.
AB  - The reactivities of sera from patients with Chagas disease or from T. cruzi
      immunized rabbits with two different lipid preparations of T. cruzi were assessed
      using epimastigote antigens. Serum reactivities were determined using a
      quantitative enzyme-linked immunosorbent assay (ELISA). Antigen 1 represents the
      lower phase obtained from crude lipid extract after Folch partition (LCL).
      Antigen 2 is a highly purified glycosphingolipid fraction (GSL). The LCL antigen
      discriminated quite well the reactivities of Chagasic patients' sera and sera
      from healthy individuals, as well as between the serum from a T. cruzi-immunized
      rabbit (TIRS) and normal rabbit serum (NRS). A strong reactivity with GSL was
      obtained with TIRS. Reactivity with GSL was also obtained with human Chagasic
      sera. Compared to a group of normal individuals, the reactions of antibodies
      directed against lipid antigens were considerably increased in sera of patients
      with Chagas disease. Chagasic sera did not differentiate between glycolipids with
      terminal beta-glucosyl or beta-galactosyl non-reducing units. They discriminated,
      however, glucosylceramides with differences in the ceramide structure. To
      determine the specificity of Chagasic sera, antibodies isolated on LCL
      immunosorbent (LCL-Ch Abs) as well as on laminin-immunosorbent (Lam-Ch Abs) were
      tested against laminin and LCL antigens. We found that Lam-Ch Abs reacted with
      murine laminin, whereas the reaction was negative with LCL. In contrast, the LCL
      Ch Abs reacted either with LCL antigens or with laminin. The reactivity with
      laminin was strong in comparison with LCL.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7807280
TI  - Measurement of free and total hydroxyproline by automated flow injection of serum
      or urine samples from maintenance hemodialysis patients with renal
      osteodystrophy.
AB  - An automated measurement of total and free hydroxyproline in serum or urine is
      presented that uses flow injection analysis. After exclusion of nonspecific
      substances, hydroxyproline was oxidized by chloramine-T and L-cysteine with
      Ehrlich's reagent. The linearity obtained was from 3.8 mumole/L to 1.22 mmole/L
      with good precision (CV < 3%). Comparison of the proposed method with HPLC
      yielded r = 0.939 as the correlation coefficient. Reference intervals of free and
      total hydroxyproline are 1.4-9.7 mumole/L, 3.8-27.2 mumole/L for serum, and 10.0
      72.5 mumole/L, 25.2-303.6 mumole/L for urine, respectively. Serum free and total
      hydroxyproline levels in renal osteodystrophy patients on maintenance
      hemodialysis (N = 71) were significantly higher than in controls (P < 0.0001).
      This method is superior to the use of HPLC with regard to stability of the color
      reaction. The measurement of serum free and total hydroxyproline is a useful
      marker for therapeutic observation of renal osteodystrophy patients.

PMID- 7807281
TI  - Simultaneous automated measurement of serum total CK and CK-MM isoform ratio in
      serum.
AB  - We automated a two-step kinetic procedure for determining serum CK-MM isoform
      ratio using an immunoinhibition method. By measuring the total CK activity and
      the residual CK activity (serum CK-MM isoform) remaining after the inhibition by
      tissue CK-MM isoform specific monoclonal antibody reagent (CK-M01) the CKMM
      isoform ratio is calculated using the difference between total CK and residual CK
      activities divided by the residual CK activity. Linearities of total CK and
      residual CK assays were < or = 7750 U/L and 2,500 U/L, respectively; within-run
      CVs of isoform ratio (N = 10) were 2.8 and 7.0% (mean 0.14 and 0.60),
      respectively. The MM3/MM1 isoform ratio obtained with the proposed method (X)
      correlated well with the results of electrophoretic method (Y) according to the
      equation: Y = 0.98X-0.3, r = 0.988. The normal reference range of isoform ratios
      obtained by assaying 1,222 serum samples from healthy subjects was 0.09-0.75. The
      isoform ratio increased after onset of chest pain, peaking at 2-6 hr thereafter.
      A mean isoform ratio of 1.86 was obtained with serum sample from 86 patients
      diagnosed as having an acute myocardial infarction (AMI). This method is accurate
      and highly sensitive, as the detection and early diagnosis of AMI can be
      completed in 10 min.

PMID- 7807282
TI  - Comparison of interferon-gamma and interleukin-4 production by peripheral blood
      mononuclear cells and isolated T cells after activation with polyclonal T cell
      activators.
AB  - Controversial data have been reported regarding the ability of peripheral blood T
      cells to secrete interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) from
      atopic patients as compared to nonatopic healthy controls. In most of these
      studies, T cells in peripheral blood mononuclear cell preparations (PBMC) were
      stimulated with polyclonal T cell activators. Some of these activators are able
      to activate cells other than T cells in the PBMC preparations which may influence
      the lymphokine levels in supernatants of PBMC. To evaluate this, we compared the
      IFN-gamma and IL-4 levels in PBMC and isolated T cell preparations after
      activation with phytohemagglutinin (PHA), Concanavalin A (ConA), anti-CD3 plus
      phorbol myristate acetate (PMA), or ionomycin plus PMA. The IFN-gamma and IL-4
      levels in the supernatants were calculated based on the percent T cells in the
      preparations. Whereas all activators induced significant IFN-gamma secretion,
      only ionomycin plus PMA stimulation induced large IL-4 secretion. In virtually
      all cases, the IFN-gamma levels calculated on a per T cell basis differed for
      PBMC versus isolated T cells. Whereas in some donors the IFN-gamma levels were
      higher in PBMC preparations than in T cells, in others it was the opposite.
      Similarly, in about one half of both normal and atopic donors tested, the IL-4
      levels of activated PBMC were 2- to 7-fold lower than levels in isolated T cells.
      The data suggest that non-T cells have a significant effect on the IFN-gamma and
      IL-4 levels in supernatants of polyclonally activated PBMC.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7807283
TI  - Detection of autoantibodies against M2, LKM-1, and SLA in liver diseases by
      standardized uniform ELISA-techniques.
AB  - Antibodies directed against soluble liver antigen (SLA), liver kidney microsomal
      antigen (LKM-1-AG), and antimitochondrial antigen M2 (M2-AMA) are critical
      serological markers for the differential diagnosis of autoimmune chronic active
      hepatitis (AI-CAH) and primary biliary cirrhosis (PBC). The exact diagnosis of
      autoimmune hepatitis and PBC is of great clinical relevance, as it leads to
      different therapeutic strategies. In the present work, a simple and reliable
      ELISA test system is described, which applies the same test principle for the
      detection of three different species of autoantibodies important for the
      diagnosis of chronic liver disease. The ELISA assays are based on a competitive
      inhibition of binding of positive standard antibodies by patients sera containing
      antibodies of unknown specificity. The purified immunoglobulins of clinically and
      serologically clearly defined patients with SLA or LKM-1 positive AI-CAH and with
      M2 positive PBC were used as coating- and detection antibodies in the ELISAs.
      From homogenized rat liver the fractionated 100,000g supernatant was employed for
      the SLA ELISA, the microsomal preparation served as antigen for the LKM-1 ELISA
      and the mitochondrial preparation was used for the M2 ELISA. In 1,500 sera of
      patients with the differential diagnosis of a hepatobiliary disease, 17 gave a
      positive signal in the SLA-ELISA, 12 in the LKM-1-ELISA, and 72 in the M2-ELISA.
      The results of the ELISAs were compared with Western blotting and
      immunofluorescence staining pattern on cryostat sections and Hep2 cells. The
      antibody profiles of several patients are described in detail.

PMID- 7807284
TI  - Laboratory diagnosis in hypertension.

PMID- 7807285
TI  - Diagnosis and prediction of pediatric HIV-1 infection and AIDS: current status.
AB  - The increase in the incidence of HIV-1 infection in women of child bearing age
      has resulted in a surge in the number of cases of pediatric AIDS. The World
      Health Organization (WHO) has estimated that the number of cases of pediatric
      AIDS worldwide will be at least 10 million by the year 2000. This alarming
      statistic underscores the need for accurate prediction and diagnosis of pediatric
      HIV-1 infection which is of paramount importance for the initiation of effective
      therapeutic interventions. Since circulating maternal anti-HIV-1 antibody
      persists in the baby for up to 21 months, early conventional serological
      diagnosis of infection is not possible. Other methods for diagnosis of HIV-1
      infection in a child less than 2 years of age have been utilized including the
      polymerase chain reaction (PCR), measurements of the HIV-1 p24 core protein and
      anti-HIV-1 IgA, as well in vitro measurements of antibody producing cells. In
      addition, the ability to predict HIV-1 infection in the child based upon maternal
      humoral immune responses to the envelope glycoprotein has also been suggested.
      This review summarizes the recent serological, biological and molecular
      methodologies used to predict and diagnose pediatric HIV-1 infection and AIDS.

PMID- 7807286
TI  - A road map for PCR from clinical material.

PMID- 7807287
TI  - Use of microplates and fluororeader for ultrasensitive enzyme immunoassay (immune
      complex transfer enzyme immunoassay) of anti-HTLV-I IgG.
AB  - Previously, an ultrasensitive solid phase enzyme immunoassay (immune complex
      transfer enzyme immunoassay) was described to detect low levels of anti-HTLV-I
      IgG in serum below those detectable by conventional methods. In this method,
      polystyrene balls as solid phase were transferred from test tube to test tube
      with tweezers. This was not only tedious but also causative of false-positivity
      by carryover, unless tips of the tweezers were washed carefully after each
      transfer of polystyrene balls. Bound enzyme activities for many samples were
      measured one by one by fluorometry using a spectrofluorophotometer. As a result,
      the assay of many samples was difficult. In the present study, microplates and a
      fluororeader were used in place to test tubes and a spectrofluorophotometer.
      Polystyrene balls were transferred quickly and easily from well to well by
      placing a microplate upside down on that containing polystyrene balls, and
      turning the two plates together upside down. Tweezers were not used for transfer
      of polystyrene balls, minimizing the possibility of false-positivity.
      Fluorescence intensities of bound enzyme activities for 96 samples were measured
      within a minute by using a fluororeader. Thus, it became easy to test many
      samples, although the sensitivity was lowered to some extent.

PMID- 7807288
TI  - Impact of parental health problems on children: concepts, methods, and unanswered
      questions.
AB  - Described conceptual and methodological issues that arise in the design and
      analysis of data from studies of the impact of parental health problems on
      children. Researchers should consider how the functional effects, duration, and
      type of exposure of parental health problems affect children's psychological
      experience. Multiple pathways (e.g., parental modeling, family socialization
      practices, and genetic factors) that affect the transmission of psychological
      and/or health risk to children need to be considered. Important methodological
      issues in this area of research include sample selection and bias, confounding
      factors, and limited assessment of family influences. Future work should identify
      factors that enhance child and family resilience to the effects of parental
      health problems. Studies are also needed to develop and test interventions to
      reduce the psychological morbidity associated with parental health problems.

PMID- 7807289
TI  - Impact of parental substance use on adolescents: a test of a mediational model.
AB  - Tested a mediational model of the relationship between parental substance use and
      adolescents' substance (tobacco, alcohol, marijuana) use with data from a sample
      of 1,775 adolescents, mean age 13.3 years, who completed a questionnaire
      including constructs from three theories of substance use. Mediational analyses
      identified five constructs involved in the relationship of parental and
      adolescent use. A structural model with latent constructs for substance use
      showed indirect effects of parental substance use through greater tolerance for
      deviance, lower behavioral control, greater perceived coping function of
      substance use, more negative life events, and more affiliation with peer users,
      plus a direct effect. Implications for the theory of transmission of risk are
      considered.

PMID- 7807290
TI  - Parental smoking, depression, and child development: persistent and unanswered
      questions.
AB  - Presented a review of the influences of parental smoking and depression on
      physical, behavioral, and cognitive development of children. The negative
      relationship between smoking and child development has been shown to follow a
      dose-response relationship and to be independent of several important confounds.
      Likewise, parental characteristics, particularly depression, have also been shown
      to be related to both smoking and child development. Since cigarette smoking is
      also linked with depression, there are many unanswered questions regarding the
      interrelationship of these three factors. Research should use a biobehavioral
      model to address the issues related to parental influences on child development.
      Suggestions are made for such an approach to studying parental smoking and child
      development which addresses the overlap between depression and parental smoking
      and their influence on child maturation.

PMID- 7807291
TI  - Children's internalizing and externalizing behaviors and maternal health
      problems.
AB  - Examined the impact of a range of health related constructs reflecting maternal
      physical symptomatology, health services utilization, subjective health status,
      depressed mood, medical-psychological complaints, and marital adjustment on
      children's internalizing and externalizing behavior problems in a community
      sample (N = 145). Physical symptomatology predicted a general second-order latent
      factor of children's behavior problems. Depressed mood predicted a primary latent
      factor of internalizing child behavior problems. Seizure symptoms, and more
      health problems in the last 4 years specifically predicted child psychosomatic
      complaints/anxiety. Thus, general physical symptoms predicted a broad spectrum of
      problem behaviors, whereas specific mental or physical health problems predicted
      similar distinct problem behavior syndromes. Implications of these results for
      identifying children at risk for psychopathology, and the relevance of social
      learning theory and a broader based family systems approach are discussed.

PMID- 7807292
TI  - Maternal HIV infection: parenting and early child development.
AB  - Examined whether support could offset the potential stress of maternal HIV
      infection with regard to parenting and early child development in two studies of
      low income, urban, drug-using mothers of infants and toddlers. In one study,
      support was provided through home intervention; in the other, support was
      measured through self-report. There were few differences in parenting and early
      child development related to maternal HIV infection. HIV+ mothers reported less
      child-related stress among their toddlers, more normative levels of child abuse
      potential following 18 months of home intervention, and displayed more positive
      involvement with their children. Results, interpreted from ecological theory,
      suggest that although the early stages of maternal HIV infection may have been
      too distal to influence the lives of high-risk mothers of infants and toddlers,
      when differences existed, HIV+ mothers demonstrated more positive attitudes and
      behaviors toward parenting and were more able to benefit from home intervention
      than HIV- mothers.

PMID- 7807293
TI  - Effects of pediatric HIV infection and prenatal drug exposure on mental and
      psychomotor development.
AB  - Examined the effects of HIV infection and prenatal drug exposure on infant
      neurodevelopmental functioning. Three groups of infants were compared: HIV
      infected infants, seroreverters, and a comparison group who were prenatally
      exposed to drugs, but not HIV. Two thirds of the HIV-infected and seroreverter
      infants were prenatally drug-exposed. Infants (ages 4-30 months) were
      administered the Bayley Scales of Infant Development. Children who were both HIV
      infected and prenatally drug exposed performed significantly lower on both the
      mental and psychomotor scales of the Bayley. Drug exposure and neurological
      dysfunction were associated with mental development, whereas neurological
      dysfunction, drug exposure, and HIV status were associated with psychomotor
      development.

PMID- 7807294
TI  - Effects of maternal hospitalization in early childhood: anticipated anxiety
      associated with an analog separation for childbirth and surgery.
AB  - Assessed early childhood anticipation of anxiety in response to analog 3-day
      maternal hospitalization for surgery or childbirth. Reaction to analog
      nonhospital separation was also assessed. Within each condition, gender effects
      were examined. Participants were 120 first-grade children at four elementary
      schools. Between-groups comparisons showed maternal separation for surgery was
      anticipated as more anxiety provoking, whereas anxiety associated with separation
      for childbirth and nonhospital separation was anticipated as similar. In general,
      within each separation situation, girls and boys anticipated similar levels of
      anxiety.

PMID- 7807295
TI  - Strabismus semantics.

PMID- 7807296
TI  - Observations on bilateral simultaneous botulinum toxin injection in infantile
      esotropia.
AB  - Botulinum toxin (BoTX) is an effective pharmacological alternative to the
      surgical management of strabismus in adults. In a previous study, we found that
      concurrent bilateral medial rectus muscle BoTX injections for infantile esotropia
      could produce stable ocular realignment without significant risk. No other
      investigators have used bilateral simultaneous BoTX injection. We report the
      results of bilateral simultaneous medial rectus BoTX injection in 57 infantile
      esotropia patients followed for a minimum of 12 months. The esotropic angle in 27
      infantile esotropia patients under 12 months of age was reduced from 43 +/- 12 to
      1 +/- 2 prism diopters. The esotropic angle in 30 infantile esotropia patients at
      a mean age of 24 months was reduced from 31 +/- 12 to 2 +/- 3 delta. Other
      variables including late onset of hyperopic refractive errors, dissociated
      vertical deviations, overacting oblique muscles, and consecutive exodeviations
      are evaluated. We regard BoTX as reliable therapy in infantile esotropia.

PMID- 7807297
TI  - Loss of fusion and the development of A or V patterns.
AB  - To test the hypothesis that loss of fusion predisposes the ocular motor system to
      the development of A or V patterns, we reviewed the pre- and postoperative
      courses of patients with intermittent exotropia overcorrected with horizontal
      muscle surgery. Of 332 patients who had surgery, 21 experienced at least 1 month
      of consecutive esotropia. An equal number of age-matched patients who maintained
      fusion postoperatively served as controls. No patient in either group had a
      preoperative A or V pattern. At the first return visit, at least 4 weeks
      postoperatively, 4 (19%) of the 21 patients with consecutive esotropia showed an
      A or V pattern, whereas none of the 21 control patients did so. At the end of
      follow up (mean of 27 months for patients with consecutive esotropia and 29
      months for controls), 9 (43%) of the 21 patients with consecutive esotropia
      showed an A or V pattern versus 1 (5%) of the 21 controls. These findings
      strongly suggest that loss of fusion is instrumental in the development of A or V
      patterns, consistent with "sensory torsion" theory of A and V pattern
      development.

PMID- 7807298
TI  - VECP evidence for binocular function in infantile esotropia.
AB  - Since commonly used clinical methods of measuring binocular function require
      subjective responses, this testing has been limited to more cooperative children,
      usually older than 2 years of age. Recently, we have begun using a clinically
      practical, visually evoked cortical potential (VECP) method to detect the
      presence of binocular neurons in infants and young children. We studied 14
      children, ages 4 to 44 months, with infantile esotropia. Nine had surgical
      correction for esotropia by the age of 2 years. Twenty-five normal infants ages 6
      weeks to 22 months served as controls. Most normal infants showed the development
      of the "beat" by 2 months of age. The "sum" VECP was not consistently present
      until age 6 months. Four of the five esotropic infants less than 1 year of age,
      demonstrated neither a "sum" nor "beat" response. All nine patients with
      corrective surgery performed before 2 years of age developed a significant sum
      response and three developed a beat. Five patients had not had surgery until
      after 2 years of age. Two developed a sum and one a beat, but none had both beat
      and sum responses. The results suggest that there is a loss of nonlinear
      binocular response in esotropic children not corrected before the age of 2 years
      and that these responses can be restored after early treatment even if not
      present at the time of surgery.

PMID- 7807299
TI  - A comparison of surgical techniques for the treatment of acquired esotropia with
      increased accommodative convergence/accommodation ratio.
AB  - The conventional surgical treatment for acquired esotropia with increased
      accommodative convergence/accommodation ratio consists of bilateral medial rectus
      recessions of graded amounts based on the distance deviation while wearing full
      hyperopic correction. This retrospective study was undertaken to determine
      whether surgery was more successful when performed for the distance or near
      deviation measured through the distance correction. Surgical success was
      evaluated by 1) long-term motor alignment of < or = 10 prism diopters of eso- or
      exotropia at distance and near, 2) sensory fusion as determined by Worth 4-Dot at
      33 cm and Randot II stereo acuity testing, and 3) the continued need for bifocal
      or spectacle correction. Nine patients underwent surgery for their distance
      deviation measured with full hyperopic correction; all (100%) were successful by
      alignment and eight of nine (89%) by sensory criteria. Twenty-five patients
      underwent surgery enhanced by 1.0 to 6.5 mm per eye over the dose of surgery for
      the distance angle (average 3.1 mm); 20 of 25 (80%) were successful by alignment
      criteria and 21 of 25 (84%) were successful by sensory criteria. Two of nine
      patients (22%) in the distance target angle group and 13 of 25 patients (52%) in
      the near target angle group were able to discontinue spectacles and maintain
      satisfactory alignment. Six of nine (67%) patients in the distance angle group
      were able to discontinue bifocals, while every patient in the near angle group
      was so benefited. No patient in the distance target angle group, but two patients
      in the near target angle group, required a second operation.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7807300
TI  - Bovine surfactant therapy and retinopathy of prematurity.
AB  - We reviewed the results of three randomized clinical trials of prophylactic
      bovine surfactant therapy on babies under 30 weeks gestational age to assess the
      effects of this treatment on the frequency and severity of retinopathy of
      prematurity (ROP). Of the 119 babies who received surfactant treatment, 54
      (45.4%) had ROP compared to 33 (47.1%) of the 70 babies in the control group.
      Stage 2 ROP or greater was noted in 10 (8.4%) babies in the treatment group and
      in 10 (14.3%) of the untreated group. Prophylactic bovine surfactant replacement
      therapy does not have a significant effect on the frequency of ROP in preterm
      babies. The severity of ROP also appears to be unaffected by surfactant.

PMID- 7807301
TI  - Plaque radiotherapy for residual or recurrent retinoblastoma in 91 cases.
AB  - Plaque radiotherapy has been used successfully as primary treatment for selected
      solitary retinoblastomas. However, there is relatively little information on its
      role as a secondary treatment after other methods have failed to control the
      tumor. We have used solitary plaque radiotherapy to treat 91 children with
      residual or recurrent retinoblastoma after failure of one or more treatment
      modalities, which included external beam radiotherapy in 63 children, plaque
      radiotherapy in 9, cryotherapy in 26, and photocoagulation in 18, for a total of
      116 treatments in the 91 children. Despite the fact that enucleation was
      considered to be the only remaining option in many of these children, tumor
      regression was achieved in 81 cases (89%) and recurrence developed in only 10
      cases (11%) during a mean follow up lf 52 months. Treatment of the recurrence
      following plaque radiotherapy in these 10 cases included repeat plaque
      radiotherapy in 6 cases, enucleation in 3 cases, and external beam radiotherapy
      in 1 case. In view of the fact that enucleation was being considered as the only
      remaining option in many of these children, control of the tumor with plaque
      radiotherapy in 89% of the cases is very encouraging. Plaque radiotherapy should
      be considered as an important option for recurrent retinoblastoma after failure
      of other methods to achieve tumor control.

PMID- 7807302
TI  - Value of bacterial culturing in the course of congenital nasolacrimal duct (NLD)
      obstruction.
AB  - The role of infection in the etiology and persistence of congenital nasolacrimal
      duct (NLD) obstruction is examined in a group of 334 infants who had conjunctival
      swabs cultured. One hundred and fifty eight (47%) of these had evidence of NLD
      obstruction and 176 (53%) did not. The types of organism grown from those with
      and without NLD obstruction were similar and occurred in almost equal proportions
      in each group. In addition, the rate of spontaneous resolution in those with NLD
      obstruction was the same, whether pathogenic bacteria were grown or not. There
      were no cases of orbital cellulitis, dacryocystitis, or ocular infection in those
      with NLD obstruction and no suggestion that secondary infection was more common
      in this group.

PMID- 7807303
TI  - A gyroscope deviometer for measurement of strabismus.
AB  - We describe a hand-held gyroscope deviometer that an examiner can use to measure
      strabismic deviations without prisms. The deviometer is ideally suited for use
      with small children who will not allow prisms to be held near their eyes, and
      adults with poor fixation in one eye. The device consists of a fixation light
      attached to a gimbal-mounted single-axis gyroscope. The gyroscope provides the
      necessary reference for horizontal deviations. Gravity provides the reference for
      vertical deviations. As the patient observes his or her reflection with the
      fixing eye in a plane mirror at the end of the room, the examiner positions the
      corneal light reflex in the pupil of the deviating eye and presses a rocker
      switch to the "reset" position, zeroing the deviometer. The examiner then aims
      the deviometer fixation light at a reflection of itself in a plane mirror located
      on the wall behind the subject and presses the rocker switch to the "read"
      position. Horizontal and vertical deviations are displayed to the nearest degree.
      The accuracy of the device is dependent upon the examiner's ability to position
      the corneal light reflex correctly in the pupil of the deviating eye.

PMID- 7807304
TI  - SKILL card results in amblyopic children.
AB  - Two experiments were undertaken to assess high contrast-high luminance (HCHL) and
      low contrast-low luminance (LCLL) visual acuity as measured with the Smith
      Kettlewell Institute Low Luminance (SKILL) card, in childhood amblyopia. In
      experiment 1, HCHL and LCLL visual acuity was measured in 11 amblyopic children
      and in 12 normal children of similar age. The results revealed that HCHL visual
      acuity was similar in the normal eyes and in the amblyopes' dominant eyes, and
      was abnormal in 91% of the amblyopic eyes. LCLL visual acuity was significantly
      worse in normal eyes compared to the amblyopes' dominant eyes, and was abnormal
      in only 64% of the amblyopic eyes. In experiment 2, HCHL and LCLL visual acuity
      was measured in seven previously tested amblyopic children, after a 5-month
      interval, and in six additional amblyopic children. In the amblyopic children who
      were tested twice, significant test-retest reliability for HCHL and LCLL visual
      acuity was found and visual acuity varied by 3.6%. The results of experiment 2
      corroborated the results of experiment 1 from the amblyopic children. It is
      concluded that visual acuity in the amblyopic eye tends to normalize under low
      contrast-low luminance conditions. In addition, the mechanism(s) underlying
      amblyopia appear also to influence the dominant eye, resulting in superior visual
      acuity under low contrast-low luminance conditions.

PMID- 7807305
TI  - Treatment of residual dissociated vertical deviation with inferior rectus
      resection.
AB  - The effectiveness of an ipsilateral 4-millimeter resection of the inferior rectus
      muscle was evaluated as a treatment of recurrent dissociated vertical deviation.
      Thirty-six patients who had an unsatisfactory outcome after 7- to 9-millimeter
      recession of the superior rectus muscle had an ipsilateral inferior rectus muscle
      resection. The dissociated vertical deviation was fully corrected in 18 patients
      and improved in 15 patients. Only three patients (8%) had an unsatisfactory
      result. Multivariate analysis of four preoperative features including the
      amplitude of the dissociated deviation, the age at diagnosis, the age at surgery,
      and the degree of amblyopia failed to define any factors that could predict
      surgical success.

PMID- 7807306
TI  - Ocular pursuit movement assessment by magnetic resonance imaging.
AB  - We describe a new technique for generating cinematic magnetic resonance images.
      This method produces more physiological imaging of extraocular muscles than our
      previous method. In addition, this technique provides more comfort for the study
      subject and results in less head movement artifact.

PMID- 7807307
TI  - A new scleral depressor for extremely premature infants.
AB  - A new scleral depressor has been designed that enables easy insertion into a
      small conjunctival sac, facilitating examination of the ocular fundus in
      extremely premature infants with retinopathy of prematurity. This new scleral
      depressor is also useful in mature infants and children.

PMID- 7807308
TI  - Retinal detachment in osteogenesis imperfecta.

PMID- 7807309
TI  - Recurrent corneal erosion in cystinosis.

PMID- 7807310
TI  - Alstrom syndrome: a case misdiagnosed as Bardet-Biedl syndrome.

PMID- 7807311
TI  - Chromogranin A and B in neuronal elements in Hirschsprung's disease: an
      immunocytochemical and radioimmunoassay study.
AB  - Chromogranin A and B (CAB) occur in several peptide hormone-producing cells and
      in neurons of the brain. The aim of the present study was to investigate the
      possible neuronal localization of these chromogranins in the ganglionic and
      aganglionic bowel in Hirschsprung's disease by immunocytochemistry and
      radioimmunoassay, using antibodies recognizing either chromogranin A or both
      chromogranin A and B. Further, the coexistence of chromogranins and other
      neuronal constituents was studied. CAB were found in nerve fibers and
      occasionally in nerve cell bodies of submucous and myenteric ganglia in the
      ganglionic bowel, indicating that at least a population of chromogranin
      immunoreactive nerve fibers is intrinsic in origin. CAB-immunoreactive fibers
      were numerous in the muscle layers of the aganglionic segment. These fibers
      contained tyrosine hydroxylase (TH), which indicates that they are adrenergic, in
      both ganglionic and aganglionic bowel. In the muscle layers of aganglionic (but
      not ganglionic) bowel, chromogranin A coexisted with galanin, neuropeptide Y
      (NPY), and vasoactive intestinal peptide (VIP). The concentration of CAB in
      smooth muscle specimens was higher in the aganglionic bowel than in the
      ganglionic bowel. Thus, chromogranins are present in the human enteric gut
      hyperinnervating the aganglionic bowel of Hirschsprung's disease.

PMID- 7807312
TI  - Role of anorectal myectomy after failed endorectal pull-through in Hirschsprung's
      disease.
AB  - Thirty-seven patients with Hirschsprung's disease (HD) underwent endorectal pull
      through (ERPT). Six children had signs and symptoms similar to those of their
      preoperative state, and their conditions did not respond to conservative therapy.
      Anorectal manometry showed high anal canal pressure in these patients. Anorectal
      myectomy (ARM), which included posterior rectal myectomy with partial internal
      sphincterotomy, was performed 6 to 55 months after ERPT. Five patients had marked
      improvement, and one had a partial response. Anal canal pressure was reduced
      significantly in all six patients. ARM is recommended after ERPT if constipation,
      abdominal distension, or repeated enterocolitis, unresponsive to conservative
      therapy, occurs. ARM should be performed before the patient is considered a
      candidate for a secondary pull-through operation.

PMID- 7807313
TI  - Long-term results of surgical treatment in infants with total colonic
      aganglionosis.
AB  - The authors describe the long-term results of the surgical treatment of total
      colonic aganglionosis (TCA) in nine boys who have been treated since 1975. The
      principal operative procedure was endorectal pull-through of the ganglionic
      ileum, with the aganglionic colon as an onlay patch. The procedure was employed
      in five infants, using the right or left colon. Ileorectostomy with an onlay
      patch was used in two patients; ileoanostomy without the patch was used in two.
      The distal end of the pulled-through ileum was, on average, 39 cm from the
      ileocecal junction. The average follow-up period was 11.0 years. Diarrhea and
      distension were temporary after the pull-through, and all patients ultimately
      tolerated normal feeding. Considering the variation in operative techniques, we
      were unable to demonstrate any advantage of one procedure over another. Z scores
      for height and weight at the last follow-up examination correlated with the
      weight gain before the definitive surgery and inversely correlated with the
      length of resected distal ileum at the time of operation.

PMID- 7807314
TI  - In situ extracorporeal shock wave lithotripsy (ESWL) for the management of
      primary ureteric calculi in children.
AB  - Lithotripsy was used to treat 19 children (3 to 16 years of age) with primary
      ureteric calculi. No attempts were made to mobilize the stones to the kidney.
      Stones were located in the upper ureter in seven patients, middle ureter in
      three, and lower ureter in nine. Stone size ranged from 5 to 25 mm (average, 10.4
      mm). All treatments were performed in the outpatient unit. Two children required
      general anesthesia, and 17 received intravenous sedation. The mean amount of
      energy used was 17.8 kV, and the average number of shock waves was 5,489. Before
      commencement of lithotripsy, two patients needed ureteric catheterization, and
      two had placement of double pigtail catheters. Of the 18 children who had
      adequate follow-up, 17 (94.4%) were completely stone-free, without any
      complication. The authors conclude that in situ extracorporeal shock wave
      lithotripsy is a safe and effective method for the treatment of primary ureteric
      calculi in children.

PMID- 7807315
TI  - Hair coil strangulation of the penis.
AB  - Strangulation of the penis caused by a coil of hair is uncommon. It can produce
      varying grades of injury that may result in a urethral fistula or even gangrene
      of the glans. Therefore it is important to be aware of this condition so that the
      strangulating hair can be removed and treatment instituted. The authors describe
      15 boys who presented with hair coil strangulation of the penis. Their age range
      was 5 to 11 years. All were previously circumcised. Three boys had a superficial
      injury, and 11 had a more severe injury that resulted in a urethral fistula. One
      boy presented with gangrene of his glans penis, which resulted in autoamputation.
      One-stage repair was performed in 10 boys. The first three had recurrence of the
      fistula, and hence the technique was modified for the remaining seven patients.
      The latter technique proved simple and satisfactory.

PMID- 7807316
TI  - Pretransplant chemotherapy in pediatric hepatocellular carcinoma.
AB  - The prognosis for pediatric patients with hepatocellular carcinoma is poor,
      except for fewer than half the patients, who can be rendered disease-free with
      conventional liver resection. Multicentric, bilobar liver cancer remains
      unresectable, even after radiation and chemotherapy. Liver transplantation alone
      for primary hepatic cancer has had limited success. Chemotherapy has been
      reserved for use after transplantation, with little demonstrable benefit. A pilot
      program of pretransplant chemotherapy was undertaken. Four adolescent patients
      with unresectable, multicentric, bilobar hepatocellular carcinoma were staged
      noninvasively, underwent chemotherapy followed by a final staging laparotomy, and
      then had liver transplantation. Three of the four patients survived and have no
      evidence of recurrence 84, 67, and 47 months after diagnosis and 76, 65, and 44
      months after transplantation. Pretransplant chemotherapy has four potential
      advantages: (1) minimized risk of posttransplant opportunistic infections, (2)
      less tumor bulk at the time of transplantation, (3) fewer local recurrences, and
      (4) a lower rate of metastasis.

PMID- 7807318
TI  - The internal mammary vein: an alternate route for central venous access with an
      implantable port.
AB  - Central venous catheterization in pediatric patients has, among other risks,
      flebitis and thrombosis, and finally occlusion of the superior and inferior venae
      cavae, making long-term catheterization and multiple venous cutdown more
      difficult. Use of the internal mammary vein might be an alternative procedure to
      provide sure and easy access to the central venous circulation. The authors
      report on a patient with multiple venous cutdown and thrombosis of the inferior
      vena cava, in whom the internal mammary vein was used for placement of a vascular
      device. The procedure is technically easy, and no special positioning of the
      patient is required.

PMID- 7807317
TI  - 230 patient years of experience with home long-term parenteral nutrition in
      childhood: natural history and life of central venous catheters.
AB  - The records of 27 pediatric patients who required parenteral nutrition (PN) for 5
      to 14.5 years (mean +/- SD, 8.5 +/- 3.8) were analyzed to determine the frequency
      of complications with their central venous catheters (CVC). This represents a 230
      patient-year experience. Patients with short bowel syndrome and chronic
      intestinal pseudoobstruction syndrome (CIPS) accounted for all but two of the
      patients. Unsuccessful medical management of the exit site or CVC infection was
      responsible for removal of 62% of the 123 CVCs. Ninety-five episodes of line
      infection occurred in 24 patients. Fifty (52%) were successfully treated without
      catheter removal. The organisms responsible for catheter removal were fungal
      (14), mycobacterium species (5), gram-positive cocci (22), or gram-negative
      bacilli (19). The CVCs were infected an average of once every 884 days. The life
      of the second CVC (23.5 +/- 17.9 months) was significantly longer than that of
      the first (P < .05). Clotting of the CVC with unsuccessful lysis of the clot was
      responsible for removal of 24%, and breakage or unsuccessful repair was
      responsible for 14%. In no patient were all possible venous sites for CVC
      placement exhausted. Patients with CIPS had substantially fewer catheter
      complications (P < .05) than did those with short bowel syndrome. In conclusion,
      CVCs can "survive" without major complications for more than a decade. Numerous
      factors contribute to the increased rate of CVC survival over time, including
      improvement in PN self-care with greater experience, improvement in teaching,
      regular follow-up of patients, better management of infection, and better ability
      to treat CVC thrombosis or breakage.

PMID- 7807319
TI  - Small bowel transplantation for pediatric short bowel syndrome: evaluation of the
      graft length required for development and the immunologic aspects relating to
      graft length.
AB  - Small bowel transplantation (SBT) is thought to be the only radical treatment for
      short bowel syndrome in childhood. It is very important that the length of the
      graft and the type of intestine be chosen carefully because this will determine
      the outcome of transplantation. This model of short bowel syndrome in the rat
      confirms that total intestinal resection results in malnutrition and failure to
      gain weight. After 10 cm of ileum was transplanted orthotopically in a syngeneic
      combination in rats with total intestinal resection, the animals gained weight.
      The authors determined that 10 cm of terminal ileum is the minimum length
      required for survival. Second, the immunologic basis of lethal graft-versus-host
      reaction (GVHR) as it relates to the intestinal graft length was also evaluated.
      Ileal grafts of 10 cm from LEW (RT1l) rats were implanted heterotopically into
      (LEW x BN)F1 rats. Ileal grafts of 10 or 40 cm were implanted from BN(RT1n) rats
      into (LEW x BN)F1 animals. A lethal GVHR always occurred after grafting a 10 cm
      ileum in the LEW/F1 combination, whereas only 17% of the BN/F1 recipients died of
      typical GVHR. However, in the latter combination, 67% lethal GVHR was induced
      when 40 cm of the intestinal graft was implanted. These results indicate that
      mesenteric lymph nodes are a major source of lethal GVHR, but gut-associated
      lymphoid tissue can also induce this.

PMID- 7807320
TI  - Resulting long-term intestinal motility in dogs following construction of a
      reversed jejunal segment after extensive small bowel resection.
AB  - To evaluate the long-term function and effective motility of a reversed jejunal
      segment after extensive small bowel resection, the authors continuously measured
      postoperative bowel motility during interdigestive and postprandial periods in
      conscious dogs 6 to 10 months after surgery. The long-term findings were compared
      with previously reported short-term results measured 2 to 4 weeks after the
      operation. In the long-term follow-up dogs with a 20-cm reversed jejunal segment
      constructed after extensive (75% to 80%) small bowel resection, the fasting
      duodenal migrating myoelectric (or motor) complex (MMC) was often interrupted in
      the jejunum above the reversed segment, and did not migrate smoothly to the
      reversed segment or terminal ileum. The MMCs arising from the duodenum
      predominantly propagated to the ileum through the inherent anatomic continuity of
      the bowel. In addition, brief small discordant contractions were frequent in the
      reversed segment and the jejunum, above the proximal anastomosis. These findings
      are similar to those of the MMC propagation pattern noted 2 to 4 weeks after
      surgery. However, the postprandial duration without duodenal MMC activity was
      significantly shorter in the dogs with long-term follow-up than in those with
      short-term follow-up (both were longer than in control dogs). Marked dilatation
      of the jejunum and reversed jejunal segment was noted across the proximal
      anastomosis. These results suggest that the transit time and passage of
      intestinal contents can be delayed and stagnated for at least 10 months after
      extensive small bowel resection with a 20-cm reversed jejunal segment.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7807321
TI  - Mesenteric defects as a cause of intestinal volvulus without malrotation and as
      the possible primary etiology of intestinal atresia.
AB  - Mesenteric defects can lead to intestinal volvulus even when the midgut is
      normally rotated. There are two types of mesenteric defects: basilar, in which
      the entire base of the mesentery is involved, and segmental, in which only an
      isolated portion of the mesentery is affected. These defects can present at any
      age, and the clinical symptoms depend on the extent of the disease and the amount
      of intestine involved in the volvulus. In the newborn, the basilar defects have
      clinical signs and symptoms similar to those of midgut volvulus secondary to
      malrotation. Similar to midgut volvulus secondary to malrotation, this is a
      surgical emergency. In older patients, basilar defects can be misdiagnosed
      because of the normal placement of the ligament of Treitz and because of failure
      to consider mesenteric defects as a possible cause. The treatment for basilar
      mesenteric defects is intestinal fixation. Intestinal volvulus secondary to
      segmental defects always presents as intestinal obstruction. In the newborn,
      these lesions may be indistinguishable from intestinal atresia. Older children
      present with intestinal obstruction of an unknown cause. Resection of the
      affected intestine is the treatment for segmental mesenteric defects. Intestinal
      mesenteric abnormalities as a cause of intestinal atresia unifies under one
      etiology all the lesions observed in intestinal atresia. Although this theory
      does not rule out other causes of intestinal atresia, intestinal mesenteric
      defects may be the primary condition under which intestinal atresia occurs.

PMID- 7807322
TI  - Creation of the isolated bowel segment in animals by omentoenteropexy.
AB  - An isolated bowel segment (IBS) was created in rats and dogs by a two-stage
      procedure. Initial coaptation of the bowel segment to the omentum
      ("omentoenteropexy") is followed by division of its mesentery several weeks
      later. The viability of the segment is maintained by angiogenesis at the
      coaptation site. Neoformed blood vessels were shown by angiographic studies, and
      in a dog the IBS was used for esophageal interposition.

PMID- 7807323
TI  - Colonization of intestinal bacteria in the normal neonate: comparison between
      mouth and rectal swabs and small and large bowel specimens.
AB  - Seventy-four New Zealand white rabbit pups were divided into four groups: group
      I, 2 days of age (n = 9); group II, 3 to 5 days of age (n = 24); group III, 6 to
      8 days of age (n = 27); and group IV, 10 to 13 days of age (n = 14). Mouth swabs
      (MS), rectal swabs (RS), small bowel specimens (SB), and large bowel specimens
      (LB) were obtained from each rabbit, incubated for 24 hours in thioglycolate
      broth, and plated on blood agar in aerobic and anaerobic environments. After 24
      hours, growth on blood agar plates were observed. All MS specimens and all but
      one RS specimen showed positive growth. Growth of both LB and SB specimens
      increased significantly with age (P < .04). In addition, SB growth was
      significantly less than RS or MS growth in groups I, II, and III (P < .05). LB
      growth was significantly less than RS or MS growth in group I (P < .01) and
      tended to be less in groups II and III (62.5% v 100% and 93% v 100%,
      respectively). These data show that nearly half of normal rabbits under 6 days of
      age have sterile small and large intestines despite almost 100% growth from
      rectal and mouth swabs. These findings partially explain the absence of
      spontaneous bacterial translocation in young rabbit pups (under 4 days of age)
      and have important implications for the prophylaxis and treatment of neonatal
      sepsis.

PMID- 7807324
TI  - Infrared laser Doppler flowmeter in the determination of small bowel perfusion
      after ischemic injury: comparison with the clearance of locally generated
      hydrogen and fluorescein angiography.
AB  - The determination of small bowel perfusion after an ischemic insult is difficult.
      Regional perfusion was determined in an animal model of neonatal intestinal
      ischemia using the techniques of laser Doppler flowmetry and the clearance of
      locally generated hydrogen. Both methods reliably measured tissue perfusion in
      the areas of maximal ischemic injury. However, considerable variability, perhaps
      owing to motion artifact, was seen in areas of patchy necrosis. The results
      suggest that the laser Doppler flowmeter is a suitable technique to measure
      tissue perfusion in areas of maximal ischemia. However, efforts to reduce motion
      artifact will be necessary if the laser Doppler is to be used in tissue sites
      where blood flow is critical for safe anastomosis. This will be a subject of
      future study.

PMID- 7807325
TI  - Sonographic diagnosis of acute appendicitis in children.
AB  - The authors performed graded compression abdominal ultrasound (US) examinations
      in children with suspected acute appendicitis, whose clinical presentation was
      atypical. Abdominal US examination results were 95% accurate, far exceeding that
      reported for other imaging modalities. The sensitivity was 86%, the specificity
      was 98%, and the positive and negative predictive values were 96% and 94%,
      respectively. A positive sonogram made the likelihood of acute appendicitis 50
      times greater compared with the pretest clinical impression. In addition, the use
      of US permitted identification of other pathological conditions that manifest
      similar symptoms and signs. The authors conclude that, with proper experience, US
      can be extremely useful in assisting the surgeon to markedly decrease the number
      of unnecessary appendectomy procedures, without increasing the risk of
      perforation.

PMID- 7807326
TI  - Duplications of the alimentary tract: clues to the missing links.
AB  - This is a review of the past 10 years' experience with duplications of the
      alimentary tract at the All India Institute of Medical Sciences, New Delhi,
      during which 14 infants and children with a total of 15 duplications were
      treated. Esophageal duplications represented the majority of cases (55%). Certain
      unexplained associations in this malformation led the authors to perform (1)
      detailed histological studies of the duplication cysts to seek explanation for
      the high incidence of gastric mucosa in their walls and its presence in
      duplications even in the distal parts of the gut, and (2) myelography and
      postmyelography computerized axial tomography scans to substantiate the spinal
      pathology. Three of four myelograms in patients with esophageal duplications
      showed an intraspinal pathology, and all three had vertebral defects.
      Histological evaluation of the cyst wall showed that gastric mucosa was the most
      common ectopic tissue in the walls of the cysts, and the tissues were in various
      primitive stages of differentiation. On the basis of these data, the authors
      hypothesize that (1) the embryonic endoderm of the entire alimentary tract has
      the potential to develop into gastric mucosa at the time of inception of
      duplications, which explains the high incidence of gastric mucosa and its
      presence in duplications even in the distal parts of the gut, (2) persistence of
      the embryonic relationship of the esophagus with the vertebral column is
      responsible for the high incidence of vertebral defects in esophageal
      duplications. The results of myelography in this series also support the theory
      of split notochord syndrome.

PMID- 7807327
TI  - Resolution of splenic injury after nonoperative management.
AB  - Numerous studies have demonstrated success with nonoperative management of
      splenic injuries in pediatric patients. However, the resolution of the splenic
      injury has not been previously evaluated. The records of 50 pediatric patients
      with splenic injuries from blunt trauma treated nonoperatively between 1984 to
      1992 were reviewed retrospectively. Abdominal computed tomography (CT) was
      performed at the time of injury and 6 weeks postinjury in 25 patients. These
      scans were reviewed and categorized by a modification of a previously reported
      grading system for parenchymal injury. All patients had healing of the splenic
      injuries, with complete resolution of the healing process observed at 6 weeks
      postinjury in 44%. Even those with shattered spleens (n = 6) had consistent
      improvement in splenic architecture, with resolution of fractures and/or
      contusions and return of splenic perfusion. Ten (77%) of 13 grade 1 and 2
      injuries were completely resolved by the 6-week follow-up examination, whereas
      only one (8%) of 12 grade 3 to 5 injuries showed radiological resolution of
      splenic injuries. None of the 25 follow-up CT scans affected clinical decision
      making or led to a deviation from the established protocol, which included a 3
      month period of reduced activity. All 50 patients did well, without evidence of
      morbidity, mortality, or complications after return to full activity 3 months
      postinjury.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7807328
TI  - Evaluation of the pediatric surgical matching program by the directors of
      pediatric surgical training programs.
AB  - In a previous survey of successful candidates (SC) and unsuccessful candidates
      (USC) to the pediatric surgery matching program (PSMP), significant
      discriminating factors associated with SC included previous participation in
      basic science research, number of publications, number of national presentations,
      and contact with and letters of recommendation from well-known pediatric
      surgeons. The purpose of this study was to determine the selection criteria used
      by directors of the pediatric surgery training programs (PSTP) in choosing
      residents for the PSMP. A two-part survey of the PSMP was completed by directors
      of the PSTP (n = 24) to identify the factors (n = 31) that most influence their
      selection process when choosing a resident, and to help clarify questions (n =
      11) posed by the candidates during the first survey. In part I, each factor was
      scored on a modified Likert Scale, from most (1) to least (5) important in
      evaluating candidates for training positions, and were ranked according to the
      mean score. Based on our previous survey, but blinded to the PSTP director
      respondents, these same factors were divided into groups that, in our first
      survey, did and did not discriminate between SC and USC for the PSMP, and will be
      referred to as "discriminating factors" (DF, n = 7) and "non-discriminating
      factors" (NDF, n = 8), respectively. Also, a series of questions dealt with
      subjective factors of the candidates, not previously analyzed in our original
      survey, and will be referred to as "program directors' factors" (PDF, n = 16).
      The three groups (DF, NDF, PDF) were analyzed by the Kruskal-Wallis test and
      analysis of variance (ANOVA).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7807329
TI  - Achalasia of the cardia in children: a worldwide survey.
AB  - This report summarizes a worldwide survey of achalasia in childhood. The data
      were obtained by circulating a questionnaire to pediatric surgeons throughout the
      world. Information was received regarding 175 patients, and the analysis is
      presented. Childhood achalasia appears to be more common in boys, and familial
      cases are rare. Regurgitation of food and dysphagia are the most frequent
      symptoms in affected children. Although 18% of patients had symptom onset during
      infancy, only 6% of the patients were identified as having achalasia during
      infancy. The survey suggests only a fair clinical response to transthoracic
      esophagocardiomyotomy and a good to excellent clinical response to transabdominal
      esophagocardiomyotomy. A cooperative effort between several institutions will
      permit the development of prospective treatment protocols for children with
      achalasia.

PMID- 7807330
TI  - Treatment of intraosseous arteriovenous fistulas of the extremities.
AB  - Intraosseous arteriovenous fistulas of the extremities are rare malformations
      frequently associated with severe systemic hemodynamic alterations. In many
      cases, it is quite difficult to eliminate these anomalous vascular structures,
      but the possibilities for successful treatment are much greater when surgery is
      combined with interventional radiology. Selective embolization of the malformed
      vessels can be produced with a variety of agents that are injected into afferent
      arteries, via percutaneous puncture or through direct surgical access. The
      intraosseous portion of the fistula should be resected at the time of
      embolization or later. The authors describe the successful treatment of three
      patients having intraosseous arteriovenous fistulas of the upper extremities, who
      have had follow-up for 2 to 10 years.

PMID- 7807331
TI  - Isolated torsion of the fallopian tube in premenarcheal girls.
AB  - The authors report on two premenarcheal girls, ages 4 and 13 years, with isolated
      torsion of the fallopian tube, an extremely rare condition. The fallopian tube
      was salvaged by detorsion in the younger girl, the first salvage described in the
      English literature on children. The mechanism of the isolated torsion and the
      clinical implications are discussed.

PMID- 7807332
TI  - Leiomyoblastoma causing acute gastric outlet obstruction in an infant.
AB  - A 1-year-old boy had acute gastric outlet obstruction, the cause of which was a
      prepyloric submucosal mass. The mass and the ulcerated overlying mucosa were
      excised. The histological diagnosis was leiomyoblastoma with parenchymatous
      hemorrhage. Apparently, he is the youngest patient reported to have this disease.

PMID- 7807333
TI  - Aldosteronoma in childhood: a review of clinical features and management.
AB  - Primary hyperaldosteronism is rare in children and usually results from bilateral
      adrenocortical hyperplasia. Adrenal adenoma causing primary hyperaldosteronism
      (aldosteronoma) in children is even rarer, with only eight reported cases in
      children under 18 years of age. Aldosteronoma is a very rare, correctable cause
      of childhood hypertension. A review of all the reported cases, including that of
      the authors, is presented. Also discussed are the available biochemical and
      radiological investigations, the preoperative medical management, the surgical
      treatment, and the postoperative management.

PMID- 7807334
TI  - Massive ovarian edema in the pediatric patient: a rare solid tumor.
AB  - Solid ovarian masses in children are considered malignant unit proven otherwise.
      The authors report two cases of an unusual, benign, solid ovarian tumor found
      during ultrasound examination for evaluation of acute abdominal pain. Both
      patients were found to have a torsed nonviable ovary at the time of laparotomy.
      Patient 1 was a premenarcheal 10 year old who had undergone a lengthy evaluation
      for intermittent chronic abdominal pain. The ultrasound examination showed a 9- x
      5-cm ovarian mass. Patient 2 was a virilized menarcheal 11 year old with a very
      large tumor (10 x 7 x 16 cm). The final pathology for both tumors was massive
      ovarian edema--a rare, stromal, virilizing tumor caused by chronic venous and
      lymphatic obstruction. Contralateral oophoropexy is a controversial treatment for
      the remaining ovary. A review of the literature regarding this uncommon tumor is
      provided.

PMID- 7807335
TI  - A pitfall in the technique of jejunal tube insertion, resulting in jejunal
      perforation.
AB  - Enteral feeding by a jejunostomy tube is a reliable and cost-effective method for
      both long- and short-term nutritional support in selected patients, although a
      high complication rate has been reported in some series. The authors report on
      jejunal perforation in an infant, caused by a kinked jejunostomy tube, and
      emphasize this possible pitfall as a warning to others.

PMID- 7807336
TI  - Catheter-induced urinary bladder rupture presenting with pneumoperitoneum.
AB  - Neonatal bladder injury is rare and usually associated with umbilical artery
      catherization. Patients may present with apparent renal failure, abdominal
      distension, and respiratory distress. Treatment involves operative closure of the
      perforation and bladder drainage. A case of Foley catheter-induced bladder
      rupture in a premature infant, not previously reported in the literature, is
      detailed.

PMID- 7807337
TI  - Superior vesical fissure associated with urethral duplication in a male neonate.

PMID- 7807338
TI  - Simple technique for proximal pouch mobilization and circular myotomy in cases of
      esophageal atresia with tracheoesophageal fistula.

PMID- 7807339
TI  - Repair of pectus excavatum using a Dacron vascular graft strut.
AB  - Long-term follow-up was obtained for 161 patients who underwent a modified
      Ravitch repair of pectus excavatum. In all cases, the substernal strut was
      fashioned from a Dacron vascular graft. Follow-up was done by telephone (most
      cases) and also by office visit (43 cases). The follow-up period was 12 months to
      21.5 years. One hundred thirty-three patients (83%) had satisfactory chest
      contour; 17 had a fair result, and 11 had frank recurrence. Risk factors for poor
      contour were an asymmetrical defect, a severe defect, and associated congenital
      anomalies. Of the three patients with Marfan's syndrome, all had recurrence. One
      hundred thirty (81%) had a satisfactory scar, and 31 had hypertrophic scars. Risk
      factors for hypertrophic scar formation were increasing age and weight, and
      tripod internal fixation used early in the series. Factors not contributing to
      clinical outcome include the sex of the patient, positive family history,
      perioperative complications, year of surgery, surgeon, and type of incision. The
      use of a Dacron strut is relatively easy and complication-free. It can be left
      permanently in situ. Long-term results have been good, except in patients with an
      extensive or asymmetrical deformity, and in those with other congenital
      anomalies, especially Marfan's syndrome.

PMID- 7807340
TI  - Primary spontaneous pneumothorax in children.
AB  - In the absence of pediatric data, spontaneous pneumothorax is managed according
      to adult guidelines. Fifty-eight patients with primary spontaneous pneumothorax
      (PSP) were treated in our center over the last 20 years. The median age was 16.7
      years, and the male:female ratio was 1.9:1. A total of 102 PSP were treated; 63%
      were left-sided. The risk of recurrence was 51% after one PSP and 56% after two.
      There were four metachronous bilateral PSP. Nonoperative management included tube
      drainage in 57% of the cases (mean extent of PSP, 53%). Forty percent of patients
      were treated by supplemental oxygen and observation, without drainage (mean
      extent of PSP, 23%). Eleven patients were treated as outpatients, with Heimlich
      valves (mean extent of PSP, 64%). Fourteen patients (28%) underwent bullectomy,
      with or without pleurodesis. Thirteen of the surgically treated patient had
      experienced at least two episodes of PSP. Primary spontaneous pneumothorax in
      children has male predominance. The risk of recurrence after one episode is
      greater than that for adults. Operative management by bullectomy, with or without
      pleurodesis, carries little morbidity, has a high success rate, and is
      recommended after the first recurrence. It is safe to manage younger children
      conservatively because the chance of recurrence is lower; thoracotomy was not
      necessary in children under 9 years of age.

PMID- 7807341
TI  - Massive chylothorax associated with lymphangiomatosis of the bone.
AB  - Chylothorax in the absence of tumor or trauma is uncommon. Lymphangiomatosis of
      the bone, although extremely rare, has been associated with chylothorax. The
      authors describe the case of a 12-year-old boy who presented with a symptomatic
      left chylothorax associated with lymphangiomatosis of the ribs, scapula, and
      clavicle. Despite tube thoracostomies and the initiation of total parenteral
      nutrition, massive losses of chyle persisted, resulting in hypoproteinemia and
      severe lymphopenia. Control of the chylothorax was achieved by a parietal
      pleurectomy and application of fibrin glue (Tisseel). In the literature there are
      16 cases of chylothorax associated with lymphangiomatosis of the bone. Their
      presentation, treatment, and outcome are reviewed. Conservative treatments such
      as dietary manipulations or thoracenteses were rarely successful. Thoracotomy
      with parietal pleurectomy on the side of the effusion is usually effective in
      controlling the chylothorax. Lymphangiomatosis should be considered a diagnostic
      possibility for any child who presents with a chylothorax.

PMID- 7807342
TI  - Use of human dura in pediatric chest wall reconstruction after tumor resection.
AB  - The most difficult aspect of the surgical treatment of chest wall tumors is
      reconstruction of the large residual defect. Materials that have been used
      include Marlex, Goretex, Vicryl, bone, metal, and fascia. The authors' successful
      experience with dehydrated human dura (Tutoplast) for moderate-size defects is
      described. A large Askin's tumor in a 13-year-old boy required resection of the
      right posterior aspect of the 9th to 11th ribs and the transverse process of T
      10, the 12- x 12-cm thoracic defect was closed with dura. Partial soft-tissue
      coverage was obtained with the latissimus dorsi muscle. Although a scoliosis
      secondary to paraspinal muscle resection has developed, the chest wall is stable,
      without evidence of a flail chest, at 18 months of follow-up. A 6-year-old girl
      underwent left anterior chest wall resection of three ribs for an epithelioid
      sarcoma. Human dura and a myocutaneous flap were used for reconstruction, with
      good functional and cosmetic results at 16 months of follow-up. Dura is simple to
      use, has low antigenicity, and in experimental studies appears to be incorporated
      into the tissues, acting as a collagen matrix. For moderate-size chest wall
      defects, it appears to be an excellent alternative to synthetic prosthesis.

PMID- 7807343
TI  - Lymphoproliferative disease after pediatric liver transplantation.
AB  - Posttransplant lymphoproliferative disease (LPD) is a serious complication,
      associated with considerable morbidity and mortality. Herein the authors report
      their experience with LPD in a series of pediatric liver recipients (from 1986 to
      1993). A total of 95 transplants were performed in 78 patients. Only the 66
      patients who survived at least 30 days were included in the analysis. There were
      seven cases of LPD (incidence, 10.65). Seven of the 43 patients who received OKT3
      had LPD, compared with none of the 23 patients who did not receive OKT3 (P <
      .05). The total cumulative dose and the duration of therapy both correlated with
      occurrence of LPD. However, the dose per kilogram did not correlate with the
      development of LPD. The median time from transplant to diagnosis was 90 days. All
      cases were immunoblastic B-cell lymphomas, and all tumors were positive for the
      Epstein-Barr viral genome (EBV). Four patients never treated for LPD died; it was
      discovered incidentally during autopsy in two, during retransplantation in one,
      and within 5 days of death in one. The other three were treated with decreased
      immunosuppression, acyclovir, gamma globulin, and alpha-interferon. All three
      were cured of LPD, but one died of neurological complications after
      retransplantation. LPD may be interpreted as a symptom of a chronically
      overimmunosuppressed state, associated with a high mortality, from a variety of
      causes. LPD should be suspected for any patient whose clinical condition is
      deteriorating with no clear evidence of rejection, and should lead to a decrease
      in the amount of immunosuppression used.

PMID- 7807344
TI  - Pediatric malignant pheochromocytoma.
AB  - Pediatric malignant pheochromocytomas are very rare tumors, and no institution
      has more than one or two of these problem cases. The authors report on two
      children with such tumors, over a 9-year period, from two hospitals. In 1984,
      D.B. (14 years of age) presented with symptoms and signs of extradural metastasis
      from a right adrenal primary; he also had lung and bone metastases. After spinal
      decompression almost 4 years. He has remained well and is in remission 6 years
      later. In 1987, G.R. (13 years of age) presented with a larger right adrenal
      malignant pheochromocytoma invading surrounding structures; he also had liver
      metastasis. Preoperative chemotherapy did not shrink the tumor much; it was
      grossly resected, and there were many postoperative problems. In 1990, bone
      metastases developed, for which radiotherapy and chemotherapy were used. Three
      years later, the metastases have not disappeared; he remains on chemotherapy, and
      his liver function is borderline. From our small experience as well as a
      literature review, it appears that surgical excision remains the treatment of
      choice for the pediatric malignant phoechromocytoma. Unresectable tumors may be
      rendered resectable by intensive chemotherapy (similar to that used for
      neuroblastoma); adjuvant chemotherapy should be used for residual disease after
      surgery and for metastatic disease.

PMID- 7807345
TI  - Report of three gastric tumors in children.
AB  - The literature concerning gastric tumors in children is mainly limited to case
      studies. The authors reviewed 1,403 histological reports of pediatric gastric
      pathology (covering 10 years) at their institution. There were three gastric
      tumors of benign histology and no malignant tumors. The first patient was a 9 1/2
      year-old boy who presented with several months of symptomatic, pH-probe-confirmed
      gastroesophageal reflux. He underwent placement of a Toupet antireflux valve.
      During laparotomy, a submucosal mass was discovered incidentally, on the greater
      curvature of the stomach. The mass was excised. Pathological examination showed
      heterotopic pancreas. The second patient, a 15-month-old girl, presented with a
      short period of vomiting. Results of an upper gastrointestinal series showed
      gastric outlet obstruction. She underwent laparotomy and was found to have an
      intussusception of a gastric polyp into the proximal jejunum, and an associated
      malrotation. Ladd's procedure, gastroduoduodenostomy with reduction of the
      intussuscepted polyp, and excision of the polyp were performed. Histological
      examination of the tumor showed hamartoma with hyperplastic elements. The tumor
      was benign but was regarded as difficult to classify. The third patient, a 6-year
      old boy, presented with microcytic anemia. Endoscopy showed multiple friable
      bleeding gastric masses. He underwent laparotomy, with partial gastrectomy and
      pyloroplasty. Histological examination showed the tumor to be plasma cell
      granuloma. The tumor recurred, and the patient required subsequent operative
      procedures. The authors confirm that gastric tumors in children are rare.
      Although the tumor histology may be benign, excision of the tumor may require
      major operative resection.

PMID- 7807346
TI  - Pure esophageal atresia: a 50-year review.
AB  - This review encompasses 50 years (1942 through 1991) and 69 newborns (43 boys, 26
      girls). Half the babies were premature (weighing less than 2.5 kg), and about one
      third had other anomalies. The procedures used in this series were late primary
      anastomosis (17), gastric tube reconstruction (16), staging esophagostomy and
      gastrostomy (13), gastric pull-up (13), early primary anastomosis (4), and colon
      replacement (3). Four neonates received no treatment. The most common repair in
      the 1940s and 1950s was the gastric pull-up; the gastric tube was the most
      popular in the 1960s and 1970s. Delayed primary anastomosis has been the
      operation of choice since the 1980s. Over the last decade, it has become apparent
      that primary repair is successful in three quarters of such infants if the wait
      is 3 months and/or the newborn weight has at least doubled. This repair appears
      to provide the best functional result, unless there is an anastomotic stricture.
      Before the 1970s, the survival rate was below 40%, but since the 1980s the rate
      has more than doubled, to 90% in our series, regardless of the type of repair
      used.

PMID- 7807347
TI  - Aortoesophageal fistula: congenital and acquired causes.
AB  - Aortoesophageal fistula (AEF) is a rare but frequently lethal cause of upper
      gastrointestinal bleeding. This is a report of the authors' experience with four
      cases--two from congenital and two from acquired causes. A review of the
      pediatric cases reported in the literature is included. The mortality from AEF is
      high, and can be decreased in two ways. AEF can be prevented by avoiding
      prolonged nasogastric intubation in patients with known vascular rings, and by
      promptly removing esophageal foreign bodies and promptly treating periesophageal
      abscesses. Once an AEF occurs, it presents with typical large-herald upper
      gastrointestinal bleeding of bright red blood, and cardiovascular collapse.
      Recognition of this pattern, with vigorous resuscitation and aggressive surgical
      management, will improve the survival rate.

PMID- 7807348
TI  - Results and complications of Toupet partial posterior wrap: 10 years' experience.
AB  - A 270 degrees posterior wrap, described by Toupet, was performed in 112 patients
      with medically refractory gastroesophageal reflux (GER) over a 10-year period.
      The mean age was 39 months (range, 2 months to 19 years). Thirty percent of the
      patients were neurologically impaired (NI). The approximation of the crura, the
      posterior fixation of the wrap, and the posterior partial fundoplication were
      performed with nonabsorbable sutures, over a bougie. Thirty percent of the NI and
      15% of the neurologically normal (NN) children underwent a gastrostomy. Early
      postoperative complications were found in 24% of NI and 18% of NN children; these
      were treated medically, except for two bowel obstructions. Eight patients died
      for reasons unrelated to surgery, and nine were lost to follow-up. The mean
      follow-up period for the 95 remaining patients was 3.5 years for NI and 4.9 years
      for NN children. The evaluation showed that 6 patients had temporary dysphagia
      and two had food impaction. Nine wrap herniations (10%) were found; three of them
      without symptoms were noted by routine upper gastrointestinal series and received
      no treatment. Six wrap herniations with recurrent reflux were reoperated on
      successfully. With 90% of patients free of symptoms, the results of the Toupet
      procedure compare favorably with those of the Nissen fundoplication because of
      the retained ability to belch or vomit.

PMID- 7807349
TI  - Thrombotic complications of saphenous central venous lines.
AB  - Authors of recent publications advocate central venous access by saphenous vein
      cutdown in the thigh. Even relatively inert SILASTIC catheters are recognized to
      convey a risk of large vein thrombosis when maintained for long periods.
      Thrombosis of the inferior vena cava (IVC) and tributaries place the patient at
      risk for a spectrum of problems not associated with superior vena cava (SVC)
      cannulation. The authors describe 46 neonatal intensive care patients with
      central venous cannulation of more than 2 weeks' duration. Prospective monitoring
      by ultrasound yielded a thrombosis rate of 16.6% for SVC cannulation and 28.5%
      for IVC cannulation. Complete occlusion of the IVC was clinically apparent and
      confirmed radiographically in four patients. In another patient, bilateral renal
      vein thrombosis developed, which contributed to her death. The authors compare
      their data for IVC and SVC cannulation and question whether the saphenous vein
      should be a primary route.

PMID- 7807350
TI  - Subcutaneous infusion ports in the pediatric patient with hemophilia.
AB  - Central venous access devices have become important tools in the management of
      pediatric patients with malnutrition, malignancy, and infections requiring long
      term antibiotic treatment. Hemophilia presents a lifetime challenge for venous
      access and at times can be an urgent or life-threatening situation. Since 1986,
      the authors have implanted 11 subcutaneous infusion ports in nine patients with
      hemophilia. The systems have remained in place for up to 7 years, without major
      complications or problems. Two catheters were replaced, after 4 and 6 years,
      because of skin erosion and blockage, respectively. One catheter was removed
      after 7 years because of blockage following local trauma and was not replaced. A
      recent survey through the Canadian Hemophilia Centre Directors Group obtained a
      further 45 subcutaneous infusion ports in other centers across Canada. The
      benefits of this system are overwhelming enthusiasm by the parents and children
      and no major complications. Some of the patients are now HIV-positive and are
      able to use their system for ongoing drug therapy.

PMID- 7807351
TI  - Nerve growth factor receptor staining of suction biopsies in the diagnosis of
      Hirschsprung's disease.
AB  - The authors studied rectal suction biopsy material in 60 consecutively treated
      patients suspected of having Hirschsprung's disease (HD) (age range, 3 days to 12
      years). According to acetylcholinesterase (AChE) staining, 10 patients had HD,
      three had neuronal intestinal dysplasia (NID), and 47 were normal. The diagnoses
      were confirmed by H&E staining of biopsy material and by examination of
      surgically resected material in the HD and NID cases. The 60 cases were stained
      with a monoclonal antibody to the nerve growth factor receptor (NGFR) using
      immunohistochemistry on fresh frozen biopsy tissue. In the 47 normal biopsy
      specimens, there was a large number of immunoreactive fibers in the lamina
      propria, and staining of the muscularis mucosae and submucous ganglia. In
      contrast, there were no immunoreactive fibers in the lamina propria in patients
      with HD and NID. A striking finding was the strong expression of immunoreactivity
      on the perineurium of submucosal hypertrophic nerve trunks in cases of HD. The
      results indicate that NGFR immunoreactivity is similar in specificity and
      sensitivity to AChE in the diagnosis of HD. Because the technique uses an
      immunocytochemical rather than a histochemical technique and the results were
      easier to interpret, NGFR staining may be an important additional technique to
      diagnose HD.

PMID- 7807352
TI  - A new look at an old operation for aganglionosis.
AB  - Since 1980, the authors have operated on seven infants with total colon
      Hirschsprung's disease using the long Duhamel procedure. All infants were given
      an ileostomy when the diagnosis was made, and the long Duhamel procedure was
      performed between 6 and 24 months of age. This operation in the standard Duhamel
      procedure except that the sigmoid and descending colon form the fecal reservoir
      (as in the Martin variation of the Duhamel operation). A covering loop ileostomy
      was made in all the patients, and it was closed within 5 months; two infants had
      one episode of enterocolitis, 1 to 9 months after closure. The seven infants have
      had follow-up for 1 to 13 years; all are alive and well. The children are
      continent and toilet trained (age not withstanding); they have up to 10 formed
      stools per day. Two had some soiling at night. Whereas in the past the Duhamel
      procedure (in which a too-long anterior rectal pouch was left) often resulted in
      the formation of a fecal impaction, this does not occur when the material passing
      through the anus is at best semiliquid. With no long side-to-side anastomosis,
      the procedure is simple and complications are few.

PMID- 7807353
TI  - A new method of intestinal salvage for severe small bowel ischemia.
AB  - The morbidity and mortality in short bowel syndrome are directly related to the
      length of the remaining small bowel and to the duration of total parenteral
      nutrition. We describe the successful salvage of an infant with extensive small
      bowel infarction for whom a new technique was used to preserve all viable mucosal
      surfaces. The infant, with gastroschisis, was found to have a tight volvulus of
      the extruded bowel and extensive small bowel ischemia at the time of delivery.
      Forty-eight hours after reduction of the volvulus and abdominal decompression, a
      second-look laparotomy was performed. Although only the terminal 13 cm of ileum
      was completely viable, 25% of the circumference of a further 23 cm of proximal
      jejunum/ileum was considered salvageable. After debridement of the dead tissue,
      the remaining gutter of jejunum was divided at its midpoint, and the two halves
      were anastomosed longitudinally to provide a "neojejunum" of 12 cm in length,
      which was anastomosed between the duodenum and terminal ileum. Full enteral
      feeding was tolerated from day 47. Although the neojejunum was excised on day
      149, after becoming dilated and atonic, by that time the remaining small bowel
      had elongated to 30 cm. Because of the early institution of full enteral feeding,
      there were no long-term complications related to total parenteral nutrition.

PMID- 7807354
TI  - Spinal anesthesia for primary repair of gastroschisis: a new and safe technique
      for selected patients.
AB  - Spinal anesthesia has been described for infants and premature babies undergoing
      minor operative procedures. The advantages of shorter operating time, avoidance
      of intubation, and shorter hospital stay have made this the gold standard for
      premature and other high-risk infants requiring minor procedures. However, little
      is known about this technique for major interventions in newborns and preterm
      infants. Recently, four infants born with gastroschisis underwent repair under
      spinal anesthesia. Two had accompanying intestinal atresia (one with a prenatal
      perforation and pan-hypopituitarism), and two had intact gastrointestinal
      systems. The gestational ages were 39, 33, 36, and 36 weeks, respectively. All
      had primary closure of the defect; one had no repair of the atresia because the
      bowel was thick and matted with a significant peel, and the defect was not
      identified. In the second case with atresia, necrosis and perforation of a
      localized segment of intestine was identified proximal to the intestinal atresia,
      and was exteriorized with the primary repair. When they arrived in the operating
      room, all four infants were breathing spontaneously, on room air, after
      appropriate fluid resuscitation. All underwent spinal anesthesia, which was the
      only agent used for the operation. The operative time was 45, 25, 30, and 25
      minutes, respectively (mean, 31.25 minutes). The duration of anesthesia was 170
      to 230 minutes (mean, 205 minutes). All infants were returned to the neonatal
      intensive care unit on room air and breathing spontaneously. One was given
      morphine postoperatively and suffered significant respiratory depression,
      requiring intubation. It appears that spinal anesthesia is safe and effective for
      major operative procedures in high-risk infants. (ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7807355
TI  - Minimally conjoined omphalopagi: a consistent spectrum of anomalies.
AB  - Omphalapagus twins constitute less than one third of all siamese twins. Most
      omphalopagi are attached by a skin bridge that often contains hepatic tissue.
      Only four cases of omphalopagi attached by an intestinal bridge have been
      reported. The authors present two additional cases of conjoined twins minimally
      attached by a small bowel and bladder bridge. In both instances, the spectrum of
      anomalies included a ruptured omphalocele and imperforate anus with cloacal
      anomalies. The attachment consisted of an open urachal remnant joining the two
      bladders, and the short small bowel of twin A attached to the terminal ileum of
      twin B. Separation was uneventful. For one set of twins, the case part of the
      proximal colon of twin B was used to lengthen the bowel of twin A. Three of the
      twins survived and underwent additional procedures for repair of the cloacal
      anomalies. All four previously reported cases of minimally conjoined omphalopagi
      presented with a remarkably similar spectrum of anomalies. All had ruptured
      omphaloceles, imperforate anus with cloacal anomalies, and urachal anomalies.
      Intestinal connection was consistently at a point corresponding to the Meckel
      diverticulum site of twin B, with blood supply to the small bowel of twin A,
      probably via the vitelline artery. The consistent spectrum of anomalies
      encountered with minimally conjoined omphalopagi allows planning of separation.
      Caution is required to avoid overlooking the patent urachus, and intestinal
      lengthening procedures based on the vitelline artery become an important
      consideration.

PMID- 7807356
TI  - Congenital absence of the portal vein: two cases and a proposed classification
      system for portasystemic vascular anomalies.
AB  - Congenital absence of the portal vein (CAPV) is an unusual condition that often
      is associated with other anomalies. This is the first report of reduced-size
      liver transplant in a patient with CAPV. Because the presence of this rare
      congenital portasystemic shunt, there was no portal-systemic pressure
      differential, and thus an absence of collateral vessels in the pretransplant
      state. As a result, surgery was complicated by severe mesenteric edema caused by
      an increase in portal pressure when the allograft was implanted. The morbidity
      associated with CAPV usually results from associated conditions, but if
      transplantation is necessary, careful management of mesenteric congestion is
      crucial to success. The authors' experience and a review of the literature
      indicate that the CAPV can be classified into one of two groups of portasystemic
      anomalies.

PMID- 7807357
TI  - Total anomalous pulmonary venous return complicating portoenterostomy for biliary
      atresia.
AB  - Cardiovascular anomalies such as absent inferior vena cava and preduodenal portal
      vein are reported in cases of biliary atresia and make hepatic portoenterostomy a
      technical challenge. The authors present the case of a severe cardiac anomaly
      that significantly altered the functional outcome of a Kasai procedure. Baby M.,
      an 8-week-old boy born with total anomalous pulmonary venous return (TAPVR),
      underwent hepatic portoenterostomy for biliary atresia. Over the next 3 months he
      remained icteric and febrile, and failed to gain weight. After multiple
      antibiotic treatments for suspected cholangitis, he underwent reexploration of
      the portoenterostomy, with no improvement in his overall condition. His prognosis
      was considered dismal because correction of the cardiac anomaly is associated
      with a high mortality rate (> 90%). The cardiac surgeon agreed to attempt a cure
      of the TAPVR, provided liver transplantation is contemplated if the patient
      survived. Within 48 hours postoperatively, his hepatic function had improved
      drastically. He became afebrile, had an improved appetite and weight gain, and
      was finally discharged 203 days after admission. One year later, he is thriving
      and remains anicteric. The exact reason for this drastic improvement is not well
      understood, but the right-sided cardiac failure caused by the TAPVR had a
      significant effect on the functional outcome of the portoenterostomy.

PMID- 7807358
TI  - Cecal volvulus in the Cornelia de Lange syndrome.
AB  - Cornelia de Lange syndrome is a congenital malformation characterized by severe
      growth failure, mental retardation, and multiple physical anomalies. A variety of
      gastrointestinal anomalies have been described, including malrotation, colonic
      duplication, and nonfixation of the colon. Two patients with Cornelia de Lange
      syndrome presented to our institution with acute distal bowel obstruction. In
      both cases, emergency laparotomy showed cecal volvulus with necrosis of the
      terminal ileum, cecum, and ascending colon, secondary to nonfixation of the
      colon. Resection and an end-ileostomy were performed and later successfully
      reversed in both patients. Intestinal obstruction is a known cause of death in
      these children, and nonfixation of the colon has been identified during autopsy.
      Parents of children with Cornelia de Lange syndrome should be counseled as to the
      possibility of bowel obstruction resulting from cecal volvulus. This awareness
      may lead to earlier identification and treatment of this potentially lethal
      gastrointestinal tract anomaly.

PMID- 7807359
TI  - Gastrointestinal mucormycosis causing an acute abdomen in the immunocompromised
      pediatric patient--three cases.
AB  - Mucormycosis is an infection caused by a ubiquitous fungus in immunocompromised
      individuals. Typically, it invades blood vessels, producing thrombosis and tissue
      infarction. This infection spans all pediatric age groups and can lead to hollow
      viscus perforation and bowel obstruction. A 30-month old male with large cell
      anaplastic lymphoma had a bowel obstruction. During emergency laparotomy, an
      ileoileal intussusception was identified, which required resection and
      anastomosis. In the pathological specimen, fungi of the Mucorales order were
      found to be associated with tissue necrosis. On the eighth day of life, a
      premature infant had abdominal distension secondary to bowel perforation. Partial
      gastric resection and multiple intestinal stomas were performed. Death occurred
      soon after, secondary to multiorgan failure. The autopsy and surgical specimens
      showed widespread mucormycosis. An adolescent had meningococcemia-induced septic
      shock. During recovery, hemorrhagic colitis developed, which led to perforation.
      The subtotal colectomy specimen showed widespread mucormycosis. The laparotomy
      findings are typical (black necrotic tissue involving the bowel), and when seen
      in the immunocompromised patient, should make one suspect gastrointestinal
      mucormycosis. Aggressive surgical debridement of devitalized tissue augmented by
      intravenous antifungal medication is the mainstay of treatment.

PMID- 7807360
TI  - Small intestinal atresia: effect on fetal nutrition.
AB  - The peak velocity for fetal weight gain occurs in the last few weeks of
      pregnancy. As the fetus matures, it swallows and absorbs an increasing amount of
      amniotic fluid, which contributes to the growth of the fetus. The authors studied
      cases of small intestinal atresia (IA) treated over 9 years to determine whether
      amniotic fluid has any nutritive role in the development of human fetus, and if
      it does, at what stage of gestation is the contribution of amniotic fluid
      significant to fetal nutrition. Fifty-nine newborns had IA (24 jejunal, 35
      ileal). Ten of the patients had associated anomalies (3 cystic fibrosis, 2
      congenital heart disease, 1 neural tube defect, 1 microcephaly, 2 malrotation, 1
      vesicoureteric reflux). Among the 24 babies with jejunal atresia, one was a twin,
      and birth weight was not recorded for another. These two patients were excluded
      from the study. Of the remaining 22 patients with jejunal atresia, 10 were born
      before 36 weeks' gestation; only five of 35 patients with ileal atresia were born
      before 36 weeks' gestation. Fourteen patients were below the 10th percentile for
      birth weight after correction for gestational age, one was born before 36 weeks,
      and 13 were born after 36 weeks. Five (41.7%) of the 12 patients with jejunal
      atresia who were born after 36 weeks' gestation were underweight, as were eight
      (26.7%) of the 30 patients with ileal atresia. Thus, it appears that amniotic
      fluid contributes to the fetal growth in the last few weeks of gestation, and the
      higher the obstruction in the small intestine, the more pronounced the effect on
      the nutrition of the fetus.

PMID- 7807361
TI  - Diamond flap anoplasty in infants and children with an intractable anal
      stricture.
AB  - After posterior sagittal anorectoplasty for imperforate anus a prolonged course
      of anal dilatations is necessary until the scar softens. Although rare, severe
      stricture after this procedure is difficult to resolve. Y-V plasty is not
      entirely satisfactory because the pedicle advanced into the anus has some
      tension, which tends to retract producing recurrent stricture. The authors
      performed a diamond-shaped island anoplasty in eight children with postoperative
      and strictures (one after an unsuccessful Y-V plasty), with prompt resolution of
      the stricture in five. The island flap anoplasty consists of a diamond-shaped
      flap of skin formed laterally, with complete separation of skin and subcutaneous
      attachments around the periphery of the flap. The skin island is supplied with
      blood from the deep tissue. An incision is made through the scarred anal ring and
      into the mucosa, a distance of half the length of the diamond, which is then
      advanced into the mucosal defect. The defect lateral to the advanced flap is
      sutured closed. The island of skin descends naturally into the anus, under no
      tension. The procedure can be performed simultaneously in the 3 o'clock and 9
      o'clock positions, and can later be repeated anteriorly and posteriorly, although
      this has not been necessary. Two of the eight children have required no
      dilatation postoperatively, a distinct advantage in the 4-year-old patient. One
      segment in one child sloughed, resulting in repeat stricture that is responding
      to dilatation. The other seven children are doing well with their colostomies
      closed.

PMID- 7807362
TI  - Plasma endothelin levels in congenital diaphragmatic hernia.
AB  - Persistent pulmonary hypertension (PPH) together with pulmonary hypoplasia
      accounts for high mortality among patients with congenital diaphragmatic hernia
      (CDH). Endothelin (ET) is a recently described endothelium-derived
      vasoconstrictor peptide with a potent and sustained effect. The authors examined
      plasma ET levels in eight patients with CDH who had respiratory distress at birth
      and in 15 age-matched controls. The plasma ET levels were measured using a highly
      sensitive and specific enzyme immunometeric assay (EIA) preoperatively,
      intraoperatively, and 24 and 48 hours postoperatively. The mean preoperative
      plasma ET level (53.9 +/- 21.1 pg/mL) of the patients was significantly (P < .01)
      higher than that of controls (5.9 +/- 4.5 pg/mL). Two patients who died before
      operation had plasma ET levels of 60 pg/mL and 82 pg/mL, respectively. Three
      patients who had PPH postoperatively continued to have high ET levels, and at 48
      hours, the mean plasma ET level in these patients was 33 pg/mL. In contrast, in
      the three patients who survived after repair of CDH, the mean plasma ET level at
      48 hours was 1.3 pg/mL. The authors further examined the lungs of two patients
      who died before operation for the expression of ET, using immunocytochemistry.
      Pulmonary endothelial cells had strong ET staining compared with control tissues.
      These findings suggest that ET may be a pathophysiological mediator of pulmonary
      hypertension in patients with CDH.

PMID- 7807363
TI  - Gastroesophageal reflux associated with large diaphragmatic hernias.
AB  - Extracorporeal membrane oxygenation (ECMO) support has improved the outlook for
      some infants who have large diaphragmatic hernias (CDH). This has resulted in a
      subset of survivors of CDH with typically larger defects, more severe pulmonary
      hypoplasia, and more associated pathologies. This report describes the authors'
      experience with gastroesophageal reflux in patients with large diaphragmatic
      hernias who require ECMO. Contrary to previous reports, this reflux was severe
      and intractable. There appears to be a component of associated gastric
      dysmotility. In treating this reflux, medical therapy and anterior fundoplication
      were not successful, and Nissen fundoplication combined with pyloroplasty was
      required to control reflux and to allow gastric feeding. On the basis of the
      authors' experience, it is recommended that patients who have gastroesophageal
      reflux after CDH repair, for whom medical management has failed, be managed
      aggressively by surgery, with early Nissen fundoplication, and pyloroplasty and
      insertion of a gastric feeding tube.

PMID- 7807364
TI  - Fryns syndrome: a rare familial cause of congenital diaphragmatic hernia.
AB  - Fryns syndrome is a rare autosomal recessive disorder characterized by
      diaphragmatic hernia and multiple anomalies. Almost all infants have died at
      birth, and survivors have had severe mental retardation. The authors report on a
      family in which three children had diaphragmatic hernia diagnosed prenatally. The
      first child died of severe pulmonary hypoplasia in the neonatal period. The
      second survived after diaphragmatic hernia repair, and was found to have Fryns
      syndrome based on the spectrum of associated anomalies and the family history. He
      has done well except for significant gastroesophageal reflux, mild developmental
      delay, and mild hypotonia. The third child's diaphragmatic hernia was diagnosed
      early during fetal life, and the parents chose to terminate the pregnancy. These
      cases illustrate the spectrum of Fryns syndrome and the importance of a family
      history in patients with congenital diaphragmatic hernia. This is the first
      report of survival of a patient with Fryns syndrome without severe mental
      retardation.

PMID- 7807365
TI  - Improved survival for congenital diaphragmatic hernia, based on prenatal
      ultrasound diagnosis and referral to a combined obstetric-pediatric surgical
      center.
AB  - Between January 1990 and January 1993, 36 patients with antenatal ultrasound (US)
      diagnosis and/or postnatal diagnosis of congenital diaphragmatic hernia (CDH)
      were referred to the authors' high-risk obstetric and pediatric hospital. Among
      the 36, there were four spontaneous abortions (11%), five deaths after live
      births (14%), one false-positive US examination, and 26 patients who underwent
      surgery, 23 of whom survived (66% overall, 74% of live births, and 89%
      postoperatively). Only one survivor had extracorporeal membrane oxygenation
      (ECMO). Thirty-five ultrasound examinations were performed in 24 patients; there
      were 18 true-positives results (51%), one false-positive (3%), and 16 false
      negatives (46%). In this series, there were 25 left-sided CDHs, eight right
      sided, one bilateral, and one central. Of the four right-sided hernias having
      antenatal US, only one was diagnosed prenatally; 15 of the 17 left-sided CDHs
      were diagnosed correctly (88%). All 19 babies with the prenatal diagnosis were
      born at the authors' institution. US diagnosis before 25 weeks' gestation and
      polyhydramnios separately resulted in a mortality rate of only 50%. Patients born
      at this institution tend to be sicker than those transferred from elsewhere, as
      reflected by the lower 1- and 5-minute Apgar scores (3.7 v 6.9, P < .001, and 5.4
      v 6.9, P < .16, respectively), lower gestational ages (37.0 v 39.2 weeks, P <
      .007), and lower birth weights (2,525 v 3,049 g, P < .02). Nevertheless,
      transferred patients had a mortality rate (3 of 15 patients, 20%) similar to that
      of nontransferred patients (5 of 20 patients, 25%).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7807366
TI  - Accuracy of Doppler sonography in the evaluation of acute conditions of the
      scrotum in children.
AB  - During a 12-month period, 65 boys (newborn to 18 years of age) with acute scrotal
      pain or swelling underwent Doppler sonography of both testes, followed by
      scintigraphy (15) and/or surgery (34) and close clinical follow-up for at least 4
      months (23). Pulsed Doppler was performed with an ATL UM8 or Quantum II
      apparatus, using 7.5- or 10-MHz transducers. In 25 patients, color Doppler was
      also used. The testicular artery was deemed patent if Doppler shifts from
      branches within the parenchyma could be found. (Doppler signals from scrotal or
      marginal arteries were considered nondiagnostic). Through surgery, 19 testicular
      torsions were noted. Seventeen were diagnosed as such with Doppler. Two boys with
      torsion were deemed normal at the time of both Doppler and scintigraphy
      evaluation. One boy had a second Doppler examination 13 hours later, which showed
      no flow. The testicle was necrotic at the time of surgery. The second boy had had
      8 hours of symptoms and had a viable testis at the time of surgery. This probably
      represented intermittent torsion. In six of the 65 cases, no signals could be
      found on either side, and they were deemed technical failures of the test.
      Doppler sonography was technically successful in 59 of the 65 patients (91%) and
      yielded a sensitivity of 89% and specificity of 100%. Comparing the normal and
      painful side helped to define technical failures. Pulsed Doppler with mechanical
      sector scanners was more sensitive than color Doppler. Intermittent torsion was
      missed with both Doppler sonography and scintigraphy. Although ultrasonography
      cannot replace clinical judgement, it may be very helpful in unclear cases.

PMID- 7807367
TI  - The feasibility of laparoscopic swenson pull-through.
AB  - The Swenson abdominoperineal pull-through is the authors' preferred treatment for
      children with Hirschsprung's disease. The present study was performed to
      determine whether this procedure's principles could be applied to laparoscopic
      techniques. The operations were performed in 13 mongrel dogs--first to optimize
      techniques, and second to observe postoperative function in the surviving
      animals. The authors found that the dog is a good model in which to study this
      procedure, and it appears possible to perform a satisfactory Swenson pull-through
      with the laparoscope.

PMID- 7807368
TI  - Effects of intraabdominal CO2 insufflation in the piglet.
AB  - Adult intraabdominal surgery performed with the minimal-access technique has
      created a revolution in surgery. This technique has remained largely unused for
      pediatric surgical procedures because of concerns regarding its safety and
      efficacy. Presently, intraabdominal insufflation of CO2 is the preliminary step
      to performing minimal access surgery. In this study, an animal model was
      developed to determine the effects of intraabdominal CO2 insufflation in the
      infant. Eight piglets (4 to 6 kg; 14 to 19 days of age) were instrumented under
      fentanyl anesthesia to allow measurement of arterial blood pressure (BP), central
      venous pressure (CVP), heart rate (HR), cardiac index (CI), inferior vena cava
      pressure (IVCp), inferior vena cava flow (IVCf), mediastinal pressure (Mp),
      partial pressure of CO2 (PaCO2), and minute ventilation (VE) at baseline and
      during 1 hour of CO2 insufflation to a pressure of 15 mm Hg and again when
      ventilation was increased to control PaCO2 levels. Continuous recording of data
      allowed time-course analysis of 15-minute blocks to determine the rate of change
      of measured variables. A second group of 6 piglets (4 to 6 kg) underwent the same
      instrumentation, but their baseline values were compared with those during N2O
      insufflation to isolate the effects of increased intraabdominal pressure. During
      CO2 insufflation alone, PaCO2 increased by 31% (P < .0001). This increase
      occurred within the first 15 minutes of insufflation and then remained stable.
      The increase was likely the result of increased CO2 absorption from the
      peritoneal cavity because VE was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7807369
TI  - Giant jejunoileal duplication: prenatal diagnosis and complete excision without
      intestinal resection.

PMID- 7807370
TI  - Melatonin and farm animals: endogenous rhythms and exogenous applications.
AB  - Studies on farm animals have contributed significantly to our increased
      understanding of basic melatonin-related physiological mechanisms, as well as to
      the regulation of reproduction and pelage in individual domestic species. This
      review concentrates on recent work on the role of melatonin in the regulation of
      porcine reproduction, cervine endocrine, and behavioral cycles and wool and
      cashmere production which has added to this knowledge base. Early studies of the
      domestic pig indicated that melatonin secretion in this species differed markedly
      from that in other domestic and laboratory animals. There is now clear evidence
      that this is not the case and that the domestic pig uses a circadian rhythm of
      melatonin release for the transduction of photoperiodic information. Apparent
      inconsistencies among reports may be due, in part, to differences in the
      conditions under which the experiments were performed and to the assay systems
      employed to measure circulating melatonin, the concentrations of which are much
      lower than in other domestic species. Appropriately administered exogenous
      melatonin advances the onset of puberty in gilts, and may prove to be effective
      in overcoming seasonal infertility in female pigs. Appropriately timed melatonin
      and/or photoperiod treatments, administered to ruminants in utero, influence the
      reproductive physiology of the offspring, indicating that even in species which
      don't develop an endogenous melatonin rhythm till some weeks postnatally,
      awareness of photoenvironment, presumably via maternal melatonin, predates birth.
      Pre- or early postnatal melatonin-related treatments also influence the
      development/cycle frequency of pelage. Areas requiring further investigation
      include the hormonal/growth factors involved, reasons for the transient nature of
      the effects in sheep and goats, and the reason for similar effects on pelage of
      augmenting or inactivating melatonin. Aspects of endogenous melatonin rhythms in
      farm species which require further study include: the significance of the
      abolition of the nocturnal melatonin peak in the sheep by prolonged short day
      exposure; the increased pineal bloodflow in sheep bred to produce high wool
      yields; the presence of high daytime melatonin levels immediately prior to the
      rut in the fallow buck; and the low amplitude of the rhythm in the domestic pig.

PMID- 7807371
TI  - Calcium, calcification, and melatonin biosynthesis in the human pineal gland: a
      postmortem study into age-related factors.
AB  - It is believed that pineal calcification may be age-associated and that the well
      demonstrated age-related decline in melatonin biosynthesis may be an expression
      of an alteration in calcium homeostasis in the pinealocyte. Prior correlations of
      melatonin to calcium deposition and age were made on the basis of radiological or
      semiquantitative analysis. In this postmortem study of 33 subjects (age range 3
      months to 65 years) calcium deposits measured by atomic absorption spectrometry
      correlated positively with age in day and night samples (day: r = 0.56, P < 0.05;
      night: r = 0.818, P < 0.001). Nighttime (2200 h to 0800 h) pineal melatonin
      content (HPLC fluorometry) was higher than daytime melatonin levels (nighttime
      3.80 +/- 0.3 vs. daytime 0.85 +/- 0.4 ng/mg protein). Nighttime calcium levels in
      the supernatant correlated negatively with melatonin content (r = -0.59, P <
      0.05).

PMID- 7807372
TI  - Effects of aging on photoperiodic responsiveness and specific 2-[125I]
      iodomelatonin binding sites in the pars tuberalis and suprachiasmatic nuclei of
      Siberian hamsters.
AB  - Siberian hamsters undergo reproductive quiescence during exposure to a short day
      photoperiod, but this response appears to diminish with age. This study
      investigated whether age-related losses in photoperiodic responsiveness may be
      related to decreases in specific 2-[125I]-iodomelatonin binding sites in the
      suprachiasmatic nuclei or pars tuberalis. Adult male Siberian hamsters (group 1:
      3-6 months of age and group 2: 9-12 months of age) were exposed to short
      photoperiod (10 hr of light/day) for 10 weeks. Profound testicular regression was
      evident in the majority of the hamsters in group 1, but in only a few of the
      hamsters in group 2. There were no significant differences between the groups in
      the density or affinity of the specific 2-[125I]-iodomelatonin binding sites in
      either the suprachiasmatic nuclei or the pars tuberalis. These findings suggest
      that the failure of older hamsters to respond to short photoperiod is not caused
      by a loss of specific 2-[125I]-iodomelatonin binding sites in the suprachiasmatic
      nuclei or pars tuberalis.

PMID- 7807373
TI  - Mode of inhibition of rat liver tryptophan 2,3-dioxygenase by melatonin.
AB  - Liver tryptophan 2,3-dioxygenase is a cytosolic enzyme that plays a crucial role
      in the regulation of circulating levels of tryptophan. Stimulation of the
      activity of this enzyme by heme enhances the catabolism of tryptophan, making
      less tryptophan available for uptake into the brain. Melatonin, the major hormone
      of the pineal gland, is shown to cause competitive inhibition of this enzyme (Ki
      = 2.70 microM). This structural analog of the substrate L-tryptophan is a
      negative homotropic cooperative modulator of the enzyme. The enzyme has a Km =
      100 microM, and the substrate concentration required for optimum activity was
      found to be 2.5 mM with substrate inhibition becoming a feature at higher levels
      of tryptophan.

PMID- 7807374
TI  - Mode of action of inhibin-like pineal antigonadotropin is different from
      melatonin during compensatory ovarian hypertrophy.
AB  - Both melatonin and pineal antigonadotropic peptides have the same end effect,
      i.e., prevention of the hypertrophic response when tested in the conventional
      compensatory ovarian hypertrophy (COH) model. The present work was undertaken to
      study the effect of melatonin and a melatonin- and steroid-free inhibin-like
      ovine pineal antigonadotropin (PI) on serum follicle stimulating hormone (FSH),
      luteinizing hormone (LH), and prolactin (PRL) following hemoiovariectomy in adult
      Holtzman rats and also to ascertain if any similarity exists in their mode of
      action during COH. While melatonin prevented the transient rise in FSH at 12 hr
      after unilateral ovariectomy (ULO), thus retaining the basal preoperative level,
      PI depressed basal levels of FSH too. In addition, melatonin suppressed PRL and
      LH levels at 12 hr and 120 hr after ULO, respectively. PI, on the other hand, had
      no effect on serum LH and PRL levels. In light of our earlier in vitro results,
      which showed a direct inhibitory effect of PI and not of melatonin on pituitary
      FSH synthesis and release, the present results indicate a dichotomy in the mode
      of action of PI and melatonin. PI acts directly at the level of the pituitary
      while melatonin may act at the level of the hypothalamus or higher brain centers
      to suppress the FSH surge and the ensuing compensatory response.

PMID- 7807375
TI  - High melatonin solubility in aqueous medium.
AB  - The pineal hormone melatonin (5-methoxy-N-acetyl-tryptamine) has been reported to
      participate in important physiological processes. Although some of its biological
      actions seem to depend on a protein receptor at the membrane surface, melatonin
      is known to interact with a large variety of tissues and cells, suggesting that
      the molecule may not necessarily interact through a specific membrane receptor at
      a specific cell. Most discussions of melatonin activity have assumed that the
      molecule is highly hydrophobic. Contrary to belief, the present work shows that
      melatonin is soluble in a purely aqueous medium up to 5 x 10(-3) M and describes
      a new method of melatonin preparation which shows the high hydrophilicity of the
      molecule. The results presented will affect the current biological hypothesis on
      the need of a melatonin carrier in the blood stream or the mechanisms which allow
      the hormone to cross the cell membrane and interact at the level of the nucleus.

PMID- 7807376
TI  - Changes in ovine pineal gland neuron-specific enolase immunoreactivity following
      bilateral, but not unilateral, superior cervical ganglionectomy.
AB  - Pineal gland tissue from control and from unilaterally or bilaterally superior
      cervical ganglionectomized (SCGX) sheep was found to contain neuron-specific
      enolase immunoreactive cells and nerve fibers. Morphological characteristics of
      pineal cells exhibiting immunoreactivity indicated that they were predominantly
      pinealocytes, while other cell types were nonimmunoreactive. Whereas bilateral
      SCGX resulted in a reduction in the size, and possibly number, of immunoreactive
      cells in the pineal, unilateral denervation did not result in any significant
      effects when compared with control pineals. Concomitant with the reduction in
      immunoreactivity in bilaterally denervated pineals was a significant increase in
      the volume of interstitial space, but not the number of nonimmunoreactive cells.
      These results suggest that sympathetic nerve fibers innervating the pineal of
      unilaterally sympathectomized sheep exhibited a degree of neural plasticity that
      resulted in denervated pinealocytes being reinnervated by remaining intact nerve
      terminals, thus preventing the occurrence of degenerative changes normally
      associated with complete loss of neural input through bilateral denervation. The
      fact that in unilaterally denervated sheep neither left nor right SCGX produced
      any discernible effects in either half of the pineal indicates that nerve fibers
      from each of the ganglia cross over to innervate the contralateral as well as the
      ipsilateral pineal half. In the stalk of the pineal an extensive network of
      immunoreactive nerve fibers was found in both the caudal and habenular
      commissures, and occasionally these fibers were observed to enter the body of
      both intact and sympathetically denervated pineals. This latter result suggests
      that the sympathetic innervation enters the pineal over its surface and not via
      the stalk.

PMID- 7807377
TI  - Elevation of cyclic GMP levels in the rat pineal gland induced by nitric oxide.
AB  - The present paper reports that nitric oxide (NO) released by sodium nitroprusside
      (SNP) is a potent activator of rat pineal cyclic GMP production without affecting
      cyclic AMP synthesis. Other drugs such as isoproterenol, vasoactive intestinal
      peptide, and peptide histidine isoleucine were ineffective in stimulating cyclic
      GMP production, but activated cyclic AMP production. However, L-arginine, the
      physiological precursor of NO, did not activate either cyclic GMP or NO
      synthesis. Because L-arginine failed to activate cyclic GMP production, results
      suggest that NO is not produced in the pineal gland, but behaves as a potent
      regulator of this cyclic nucleotide.

PMID- 7807378
TI  - Interaction between melatonin and estradiol on morphological and morphometric
      features of MCF-7 human breast cancer cells.
AB  - Melatonin has been shown to have a direct inhibitory effect on the proliferation
      of estrogen-responsive MCF-7 human breast cancer cells, involving an interaction
      with estradiol. The anti-proliferative effect of melatonin is reversed by the
      addition of estradiol to the culture. In the present study, we examined whether
      inhibition by melatonin and subsequent estrogen rescue of MCF-7 cells are
      correlated with morphological and morphometric changes in these cells. After 4
      days of exposure to melatonin, MCF-7 cells showed significantly smaller cell and
      nuclear sizes than other groups. These morphometric results were closely related
      to the ultrastructural features observed in these cells. While control and
      estradiol-treated cells showed increased tumor characteristics, melatonin-treated
      cells presented greater differentiation, in keeping with their epithelial origin
      (presence of cytokeratin filament bundles, conspicuous rough endoplasmic
      reticulum, and Golgi cisternae together with the presence of prominent nucleoli
      at the nuclear level). Additionally, some melatonin-treated cells displayed
      degenerative features (mitochondrial swelling with disruption of cristae,
      cytoplasmic vacuolation, nuclear chromatin disgregation and cell lysis). The
      addition of estradiol to cells previously incubated with melatonin reversed the
      changes induced by the latter and these cells showed the same ultrastructural
      features as the control cells. Our results support the notion that melatonin
      exerts its antitumor effect through a cell-cycle-specific mechanism by delaying
      the entry of MCF-7 cells into mitosis. This allows the tumor cells to achieve
      greater differentiation. The fact that the morphometric and morphological effects
      induced by melatonin are counteracted by estrogens suggests a cell-cycle
      acceleration induced by estradiol.

PMID- 7807379
TI  - [Synthesis and functional studies on nucleic acids. Problems related to synthetic
      ras genes].
AB  - Synthesis of a gene for an oncoprotein, ras p21 and its functions are described.
      Point mutations in hot spots of ras genes have been found in human cancer cells
      and produce activated p21 which result in transformation of cultured NIH3T3
      cells. To produce normal and activated p21 in quantity for biochemical and
      structural studies, genes encoding these proteins were synthesized and expressed
      in E. coli. Normal and activated RAS proteins were tested for their GTPase
      activity and three dimensional structures were determined by X-ray
      crystallography. Transforming activities of the synthetic genes have been tested
      by transfecting their expression vectors to NIH3T3 cells and the synthetic
      activated genes were found to transform these cells indicating that the product
      of the activated gene is responsible for these malignant growth of the cells.
      These activities were proved to be inhibited by transfecting designed ribozyme
      genes. These synthetic genes were used to investigate mutagenesis of damaged
      bases such as 7,8-dihydro-8-oxoguanine and thymine photodimers, by introducing
      the damaged base in hot spots of the oncogene. These unnatural bases in the ras
      gene were found to be mutagenic and cause malignant growth of NIH3T3 cells.

PMID- 7807380
TI  - [Vasodilator nerves].
AB  - In addition to sympathetic vasoconstrictor nerves, nonadrenergic, noncholinergic
      vasodilator nerves control the vascular tone. In cerebral arteries of various
      species of animals, nitric oxide (NO) is a potential candidate for the
      vasodilator transmitter. In rat mesenteric arterioles, calcitonin gene-related
      peptide (CGRP) functions as a transmitter. In guinea pig mesenteric arteries,
      multiple transmitters including NO and CGRP mediate the vasodilator response. The
      physiological and pathophysiological significance of vasodilator nerves is to be
      determined.

PMID- 7807381
TI  - [Specific assay for endotoxin using immobilized histidine. Application to serum
      sample].
AB  - The amount of endotoxin in the serum was measured by the new assay method of
      endotoxin using a filtercup, Limulus amebocyte lysate, and immobilized histidine
      which is a specific adsorbent for endotoxin. The maximum recovery of endotoxin in
      the rabbit serum was obtained using acetate buffer (pH 5.5, mu = 0.1) for the
      adsorption. Using this buffer, various kinds of endotoxin in water were adsorbed
      quantitatively on immobilized histidine, and the activity of the adsorbed
      endotoxin was well recovered. The value of the amount of endotoxin in the bovine
      serum measured by the new assay method, which includes heat treatment (70 degrees
      C, 10 min) after separation followed by washing, was closer to that calculated
      from pyrogenic activities in rabbits than that measured by the PCA-Toxicolor
      method.

PMID- 7807382
TI  - [Synthesis of ethyl 1-(Difluoro-1,3,5,-triazinyl)-2-methylindolizine-3
      carboxylate as a fluorescent derivatization reagent and its reactivity].
AB  - Ethyl 1-(difluoro-1,3,5-triazinyl)-2-methylindolizine-3-carboxylate was found to
      be a selective fluorescence derivatization reagent for primary and secondary
      amines. The reagent reacted with amines in aqueous acetonitrile in the presence
      of sodium hydroxide to give the corresponding fluorescent products, which could
      be separated on a TSK gel ODS-80TM reversed-phase column with aqueous methanol as
      eluent. 2-Phenethylamine and spermidine were used to investigate the
      derivatization conditions. The detection limits (signal-to-noise ratio = 3) of
      each compound were 3 and 2 pmol per 10 microliters injection volume,
      respectively. Alcohols, thiols and aromatic amines did not give any fluorescent
      products under these derivatization conditions.

PMID- 7807383
TI  - 1994 William J. Stickel Gold Award. Contact characteristics of the ankle joint.
      Part 2. The effects of talar dome cartilage defects.
AB  - Variations in ankle joint contact characteristics caused by articular defects of
      the talar dome were investigated in 14 fresh-frozen cadaver specimens using
      pressure-sensitive film. Intact ankle and foot specimens were mounted in a
      materials tester on a loading frame which allowed positioning in neutral, and 20
      degrees of dorsiflexion and plantarflexion. Joint contact prints were recorded
      while an 800 N load was axially applied through the leg. Specimens were randomly
      placed into two lesion groups: either anterolateral or posteromedial. During
      testing, each specimen had four concentrically placed lesions on the talar dome,
      graduated in size. Following removal, the film transducers were digitized along
      with pressure calibration prints. The images were analyzed quantitatively to
      determine contact areas, mean contact pressures, ratio of to contact plafond
      areas, and high pressure centroid position as a function of lesion size and
      location. The results demonstrated significant changes in contact characteristics
      for larger lesions (> or = 7.5 x 15 mm) (P < 0.05). These findings suggest that
      determining the size of a lesion may assist in predicting the long-term outcome
      of ankles with cartilage defects.

PMID- 7807384
TI  - 1994 William J. Stickel Silver Award. Closing base wedge versus Austin
      bunionectomies for metatarsus primus adductus.
AB  - Hallux abducto valgus with concomitant metatarsus primus adductus was treated by
      either an isolated Austin bunionectomy or by a combination of a modified McBride
      bunionectomy, along with a closing base wedge osteotomy, on a total of 73
      patients (88 feet) from 1983 to 1993. Both subjective and objective similarities
      and differences were compared between these two groups of patients. Long-term
      elevation or depression of the first ray was analyzed by using a technique termed
      sagittal plane displacement. The prevalent preoperative symptoms were
      significantly reduced postoperatively in both groups of patients. Initial
      postoperative elevation of the first ray occurred in approximately one third of
      the cases in both groups. Long-term elevation of the first ray was greater with
      the base wedge osteotomy and did not change appreciably with the Austin
      procedure. The sagittal plane displacement method is a helpful tool in analyzing
      changes in the position of the first ray perioperatively.

PMID- 7807386
TI  - Pigmented villonodular synovitis. Pedal manifestations.
AB  - Although pigmented villonodular synovitis is a benign process, the potential of
      osseous destruction makes it a difficult case to manage. The treatment of
      pigmented villonodular synovitis often necessitates multiple surgical procedures
      with prolonged periods of nonweightbearing. Recalcitrant pain is often a sequela,
      secondary to nerve impingement.

PMID- 7807385
TI  - 1994 William J. Stickel Bronze Award. Amino acids, dipeptides, and leg skeletal
      muscle wound healing in diabetes.
AB  - The authors determined the effects of active amino acids and dipeptides as
      anabolic agents on surgically induced wound healing in lower extremity skeletal
      muscles in diabetic and normal rats. In order to induce diabetes, adult male
      Sprague-Dawley rats (200 g; 10 to 12 animals per group) were injected with
      streptozotocin (65 mg/kg) 30 days before the onset of the experiment. Their blood
      sugars were checked at this time. Each group of rats was injected with either one
      stimulatory amino acid or dipeptide (150 mg/kg body weight) subcutaneously in
      saline for 7 days and their anabolic effects (RNA, DNA, protein, and collagen
      contents) on lower extremity skeletal muscle wound healing determined in both
      diabetic and normal control groups. It is hoped that a treatment regimen will be
      developed using synergistic anabolic agents locally to decrease the lower
      extremity muscle healing time. This will enable the diabetic patient to become
      mobile sooner after surgery.

PMID- 7807387
TI  - Sterilization of contaminated burrs.

PMID- 7807388
TI  - Dysplasia epiphysealis hemimelica affecting the subtalar joint.
AB  - The case presented here is unique because of the location of the lesions and the
      extent to which the foot was affected. A two-stage procedure was performed
      because of the degree of bone deformity. The first stage of the procedure was
      directed at reducing osseous proliferation; the second stage addressed the
      frontal and transverse plane deformities. One-stage procedures can be used in
      treating less severe deformities.

PMID- 7807389
TI  - Electronic fetal monitoring competency--to validate or not to validate: the
      opinions of experts.

PMID- 7807390
TI  - Obstetric postanesthesia nursing: a staff education program.
AB  - The same standards of nursing care must be provided to all postanesthesia
      patients, whether these are general surgical patients or those who have received
      regional or general anesthesia associated with vaginal or cesarean birth. Because
      obstetric nursing personnel have not had the benefit of didactic and skills
      training in the area of postanesthesia nursing, additional training is mandated.
      The article describes a staff education program designed as an educational
      framework to enhance the knowledge base and assessment skills of obstetric nurses
      providing postanesthesia care.

PMID- 7807391
TI  - Cross-training in perinatal units.
AB  - Health care economics of the 1990s has brought many changes to nursing practice.
      Perinatal nursing has not escaped this change. The role of providing cost
      effective, client-focused perinatal care to mothers and infants has become an
      increasingly difficult task. With these changes, it has become imperative for
      perinatal nurses to cross-train in other areas to survive into the next decade.
      This article presents information to plan, implement, and evaluate a successful
      cross-training program.

PMID- 7807392
TI  - Integrating developmentally supportive caregiving into practice through
      education.
AB  - Implementation of developmental caregiving is occurring in intensive care
      nurseries across the country. Sound theories of adult learning, program planning,
      and change principles must be utilized to guide this process and to provide a
      framework for program design. If leaders and change agents are aware of these
      concepts and use them to make the process easier, integration should be less
      painful and the concepts promptly instituted into routine practices. Neonatal
      Individualized Developmental Care and Assessment Program research has
      demonstrated positive outcomes. This research has provided us with a vision to
      guide our practice, but change theory and education of staff also need to be
      addressed in this process.

PMID- 7807393
TI  - Journey of change: building a bridge between neonatal nursing education and
      practice.
AB  - Faculty of a post-basic registered nurse preparation neonatal intensive care
      nursing education program in Canada questioned how well students' knowledge
      equipped them to handle the demands of the clinical setting. The response to
      their inquiry prompted the abandonment of traditional teaching approaches and
      laid the foundation for a modification of the curriculum. The faculty developed a
      novel way of looking at the program's content, so that it centered on the needs
      of the neonate. The article introduces a unique neonatal nursing framework and
      explains how this framework fits with neonatal nursing education and neonatal
      nursing. This framework has potential usefulness for inservice, orientation, and
      outreach programs.

PMID- 7807394
TI  - Work redesign in the neonatal intensive care unit: role development and training
      from an educational perspective.
AB  - This article addresses educational perspectives in the neonatal intensive care
      unit patient care restructuring process at University Medical Center (UMC),
      Tucson, Arizona. An overview of patient care restructuring concepts and the
      specifics of the UMC model are discussed. The role of assistive personnel in the
      NICU is reviewed in light of available guidelines and position statements.
      Strategies to facilitate the NICU restructuring process and evaluation mechanisms
      used are listed. The curriculum development process for training of the
      respiratory therapist in an expanded nursing support role is described, and
      critical aspects of the orientation plan are identified.

PMID- 7807395
TI  - Nursing our image.

PMID- 7807396
TI  - Caring for the depressed elder.

PMID- 7807397
TI  - Christmas depression.

PMID- 7807398
TI  - The other view from the bedside: the nurse as a patient.

PMID- 7807399
TI  - Continuous quality improvement: principles and techniques.

PMID- 7807400
TI  - When your patient talks about suicide.

PMID- 7807401
TI  - Tuberculosis is making a comeback.

PMID- 7807402
TI  - Challenges met.

PMID- 7807403
TI  - Postanesthesia care of the pallidotomy patient.
AB  - The pallidotomy patient presents a challenge in the PACU. The PACU nurse should
      be knowledgeable about the pathophysiology of Parkinson's disease and the
      medications used to treat it. Prevention of postoperative complications depends
      on the PACU nurse's collection of baseline data and development of ongoing
      assessment. As the population ages, it is conceivable that pallidotomies may be
      performed on a more frequent basis. The PACU nurse has the opportunity to improve
      the outcomes for this specific population of patients.

PMID- 7807404
TI  - Parents' perceptions of the stressors of pediatric ambulatory surgery.
AB  - The economic reality of skyrocketing health care costs has dramatically
      stimulated the shift from inpatient to outpatient surgery in the last decade.
      Although the stress of inpatient surgery and hospitalization is well documented
      in the literature, little has been written about the stressors of families whose
      children undergo day surgery. This descriptive study explored the perceptions of
      parents' stressors as their children underwent day surgery. The following
      categories of parental stressors were identified: intrapersonal, interpersonal,
      or extrapersonal. Recommendations to minimize the stressors of families are
      given. Results of the study may guide planning and implementation of nursing
      practice changes in pediatric ambulatory surgery.

PMID- 7807405
TI  - Epidural diet regimen.
AB  - Continuous quality improvement presents many avenues for change. We decided to
      evaluate the number of complaints of nausea and vomiting from patients receiving
      preservative-free (PF) epidural morphine reinjections. A systematic study of this
      problem involved a survey of all patients receiving epidural pain management.
      Staff from the Department of Anesthesia and pain management nurses monitored the
      results, and after 2 months recommendations were made to change the diet of these
      patients for the first 24-hour postoperative period. Only those patients who
      received PF epidural morphine reinjections had problems with nausea and vomiting.
      Therefore, only these patients were started on the epidural diet regimen. After
      several modifications of the diet, we found that there were 80% less complaints
      of nausea and vomiting in patients adhering to this diet plan while receiving PF
      epidural morphine.

PMID- 7807406
TI  - Postoperative administration of aerosolized medications: Part I--The basics.
AB  - Based on the content of this article, the reader should be able to (1) describe
      the advantages and disadvantages of instituting drug delivery using the
      inhalation route; (2) verbalize factors that impact on aerosol deposition within
      the lung; (3) list the various types of aerosol-generating devices; (4) describe
      the benefits of incorporating a spacer device with the metered dose inhaler; and
      (5) identify and be familiar with the major categories of aerosolizable agents.

PMID- 7807407
TI  - A new dimension of the PACU: the dilemma of the ICU overflow patient.
AB  - With the increase in the number of critically ill patients needing extended
      periods of time in the ICU and the subsequent shortage of ICU beds, hospitals
      have examined ways to use the PACU as an alternative for the short-term
      critically ill patient. This article identifies common problems encountered by
      the PACU staff, and the author suggests criteria for establishing and
      implementing guidelines for successful integration of these short-term critically
      ill patients without losing sight of the PACU's goals and compromising patient
      care. The criteria for establishing guidelines were based on the personal
      experience of the author in developing a program for ICU overflow patients, as
      well as from experiences of other PACU nurses working in PACUs where successful
      guidelines currently are used.

PMID- 7807408
TI  - Intercostal nerve block.
AB  - The intercostal nerve block is an effective and relatively safe intervention for
      postoperative pain control after upper abdominal and thoracic surgery. It may be
      done in the operating room or in the PACU. Understanding the mechanics of the
      technique can help to improve care of patients receiving this intervention.

PMID- 7807409
TI  - Reading research critically: threats to internal validity.
AB  - Internal validity refers to the extent to which it is possible to attribute the
      change in the dependent or outcome variable in a study to manipulation in the
      independent variable. This article will discuss the frequent threats to internal
      validity and how to recognize them.

PMID- 7807411
TI  - Black holes and the chocolate cake concept.
AB  - The force of black holes in the universe is compared with the intense
      gravitational fields that we must navigate in our personal galaxy. Stressed by
      the many demands of home, work, and community, we are in danger of slipping into
      the black holes present in every aspect of our lives. The Chocolate Cake Concept
      is offered as a means of avoiding the black holes by breaking down barriers that
      influence our attitudes.

PMID- 7807412
TI  - Begin with the end in mind.

PMID- 7807410
TI  - Building bridges to the future.
AB  - Although it is important to stay current on the issues that are facing managers
      as health care undergoes reform, it is equally important to be aware of the
      emotional impact these changes are having on those involved. Knowing how to
      manage the personal impact of change is a major step toward leading your staff
      through the "white water" of change.

PMID- 7807413
TI  - Phase advances of circadian rhythms in somatostatin depleted rats: effects of
      cysteamine on rhythms of locomotor activity and electrical discharge of the
      suprachiasmatic nucleus.
AB  - Somatostatin is synthesized in the suprachiasmatic nucleus (SCN), a circadian
      pacemaker in mammals. To explore the functional significance of somatostatin in
      the circadian system, we examined rhythms of rat locomotor activity and
      electrical firing rate of SCN neurons in the brain slice after temporal depletion
      of somatostatin levels in the SCN. Intraperitoneal administration of cysteamine
      (200 mg/kg), a somatostatin depletor, significantly reduced somatostatin level in
      the in vivo SCN 5 min after injection and kept low level as long as 3 to 4 days.
      This administration, on the other hand, induced significant phase advances of
      about 51 min in the subsequent free-running rhythm of locomotor activity of the
      rat. A marked phase advance in the circadian rhythm of firing rate in the SCN was
      also observed after administration of cysteamine in coronal hypothalamic slices.
      These persistent phase shifts after administration of a somatostatin depletor may
      suggest that the change of somatostatin level in the SCN have a feedback
      influence on the circadian pacemaker.

PMID- 7807414
TI  - Olfactory physiology in the Drosophila maxillary palp requires the visual system
      gene rdgB.
AB  - We describe the kinetics of odorant response in the maxillary palp of Drosophila,
      and show that the rate of recovery from odorant stimulation is affected by
      mutation of the rdgB (retinal degeneration B) gene. We use immunocytochemistry to
      confirm that the rdgB gene product is expressed in the maxillary palp. rdgB has
      recently been shown to encode a protein with Ca(2+)-binding sites and sequence
      similarity to rat brain phosphatidylinositol transfer protein; it is located near
      the rhabdomeric membranes in photoreceptor cells, where it has been suggested to
      play a role in membrane transport. The delay in recovery kinetics that we observe
      in olfactory tissue may reflect a defect in membrane restoration at the
      conclusion of the olfactory transduction cascade. The use of common molecules in
      the physiology of two olfactory organs, and in both visual and olfactory
      physiology, is discussed.

PMID- 7807415
TI  - Modulation of swimming behavior in the medicinal leech. III. Control of cellular
      properties in motor neurons by serotonin.
AB  - Expression of swimming in the medicinal leech (Hirudo medicinalis) is modulated
      by serotonin, a naturally occurring neurohormone. Exogenous application of
      serotonin engenders 'spontaneous' swimming activity in nerve-cord preparations.
      We examined whether this activity is due to enhanced participation of swim motor
      neurons (MNs) in generating the swimming rhythm. We found that depolarizing
      current injections into MNs during fictive swimming are more effective in
      shifting cycle phase in nerve cords following serotonin exposure. In such
      preparations, the dynamics of membrane potential excursions following current
      injection into neuronal somata are substantially altered. We observed: 1) a
      delayed outward rectification ('relaxation') during depolarizing current
      injection, most marked in inhibitory MNs; and 2) in excitor MNs, an enhancement
      of postinhibitory rebound (PIR) and afterhyperpolarizing potentials (AHPs)
      following hyperpolarizing and depolarizing current pulses, respectively. In
      contrast, we found little alteration in MN properties in leech nerve cords
      depleted of amines. We propose that enhanced expression of swimming activity in
      leeches exposed to elevated serotonin is due, partly, to enhancement of
      relaxation, PIR and AHP in MNs. We believe that as a consequence of alterations
      in cellular properties and synaptic interactions (subsequent paper) by serotonin,
      MNs are reconfigured to more effectively participate in generating and expressing
      the leech swimming rhythm.

PMID- 7807416
TI  - Modulation of swimming behavior in the medicinal leech. IV. Serotonin-induced
      alteration of synaptic interactions between neurons of the swim circuit.
AB  - Serotonin enhances the expression of swimming in the medicinal leech Hirudo
      medicinalis. These two reports examine the physiological causes underlying this
      modulation. The initial paper (Mangan et al. 1994) demonstrated that serotonin
      enhanced the participation of inhibitory swim motor neurons (MNs) in the
      generation of the swimming rhythm in the isolated nerve cord. In experiments
      reported here, we examined whether synaptic interactions between neurons of the
      swim circuit are altered by serotonin. Following exposure to 50 microM serotonin,
      pairwise intracellular recording revealed the presence of a time-dependent
      synaptic decrement. Synaptic decrement was characterized by: 1) a substantial
      decline in synaptic inhibition (half-decay time about 0.4 s) during constant
      presynaptic excitation; 2) a reduced half-time of recovery from synaptic
      inhibition; and 3) a strong dependence on the presynaptic neuron's membrane
      potential. We found little alteration in the physiology of synaptic transmission
      involving MNs following amine depletion in leech nerve cords. We propose that
      alterations in synaptic interactions resulting from exposure to elevated
      serotonin levels, coupled with the changes in MN cellular properties described
      earlier, are crucial to the increased efficacy of MNs in participating in
      generating and expressing the leech swimming rhythm.

PMID- 7807417
TI  - Quantifying relative importance of maxillary palp information on the olfactory
      behavior of Drosophila melanogaster.
AB  - Maxillary palps have been proposed as secondary olfactory organs, after the
      antennae, in Drosophila melanogaster. Our study tries to establish the
      quantitative importance of both organs as olfactory information mediators. Dose
      response curves for three odorants: ethyl acetate, propionaldehyde and
      benzaldehyde were carried out for comparing olfaction in either complete animals
      or flies surgically deprived of antennae. Antennaless flies tested in our
      behavioral assay showed indifferent, attractant and repellent responses depending
      on concentration, similarly as normal flies do. However, they clearly displayed
      less sensitivity than normal flies. The range of concentrations they were able to
      perceive was correlated to antennal sensitivity approximately by a factor 1:10
      for ethyl acetate and benzaldehyde, and between 1:10 and 1:100 at high
      concentrations of propionaldehyde. A complementary experiment was performed to
      test changes in olfactory behavior produced by removing maxillary palps in the
      presence of antennae. At high concentrations of odorant, responses to ethyl
      acetate and propionaldehyde experienced small changes when both palps were
      removed. Results are compatible with a summation model of all olfactory
      information reaching the brain either through antennae or palps.

PMID- 7807418
TI  - Correlation between circadian periods and cellular activities in Paramecium
      bursaria.
AB  - Paramecium bursaria shows a circadian rhythm of photoaccumulation:
      photoaccumulation is stronger during the day than at night. We obtained five
      strains of P. bursaria having different circadian periods under continuous light
      conditions, ranging from 20.9 to 27.9 h. Various physiological activities were
      compared in the cells of these strains. The periods of contractile vacuole
      contraction were in the range 10-15 s, which was almost proportional to the
      periods of the circadian rhythm in each strain. Swimming velocities were
      inversely proportional to the circadian period; i.e. swimming velocities were
      high in strains whose circadian periods were short. Resting membrane potential
      was more depolarized in strains with longer circadian periods. Finally, the
      membrane resistance of the resting state was reduced in proportion to the
      increase of the circadian period. Such correlation between the cellular
      properties and the circadian period suggests that the circadian clock mechanism
      is associated with various physiological activities of the cell.

PMID- 7807419
TI  - A persistent sodium current contributes to oscillatory activity in heart
      interneurons of the medicinal leech.
AB  - 1. Normal activity in bilateral pairs of heart interneurons, from ganglia 3 or 4,
      in the medicinal leech (Hirudo medicinalis) is antiphasic due to their
      reciprocally inhibitory connections. However, Ca(++)-free Co(++)-containing
      salines lead to synchronous oscillations in these neurons. 2. Internal TEA+
      allows expression of full plateaus during Co++ induced oscillations in heart
      interneurons; these plateaus are not blocked by Cs+. Similar plateaus are also
      observed with internal TEA+ alone, but under these conditions activity in heart
      interneurons from ganglia 3 or 4 is antiphasic. 3. Plateaus in heart interneurons
      induced by Co++ and internal TEA+ involve a conductance increase. 4. A voltage
      dependent inward current, IP, showing little inactivation, was isolated using
      single-electrode voltage-clamp in heart interneurons. This current is carried at
      least in part by Na+; the current is reduced when external Na+ is reduced and is
      carried by Li++ when substituted for Na+. 5. Calcium channel blockers such as
      La3+ and Co++ block neither the TEA+ induced plateaus nor IP, suggesting that Na+
      is not using Ca++ channels. Moreover, IP is enhanced by Ca(++)-free CO(++)
      containing salines. Thus, IP is correlated with the TEA(+)- and Co(++)-induced
      plateau behavior.

PMID- 7807420
TI  - Tactile size discrimination by a California sea lion (Zalophus californianus)
      using its mystacial vibrissae.
AB  - The capability of a blindfolded California sea lion (Zalophus californianus) to
      discriminate diameter differences of circular discs by means of active touch with
      its mystacial vibrissae was studied. Using a forced choice paradigm the sea lion
      was required to choose the larger of two simultaneously presented perspex discs.
      Absolute difference thresholds (delta D) were determined for 3 standard discs
      (1.12 cm phi, 2.52 cm phi, 8.74 cm phi) by the psychophysical method of
      constants. Increasing disc size resulted in an increase in the absolute
      difference threshold from 0.33 cm for the smallest disc size to 1.55 cm for the
      largest disc size. The relative difference threshold (Weber fraction) remained
      approximately constant at a mean value of 0.26. According to a video analysis the
      sea lion did not move its vibrissae when touching the discs. Instead, it
      performed precisely controlled lateral head movements, with the touched disc
      located centrally between the vibrissae of both sides of the muzzle. Since the
      extent of these head movements was identical at discs to be compared, discs of
      different size must have led to different degrees of deflection of vibrissae
      involved in the tactile process, resulting in quantitatively different mechanical
      stimulations of mechanoreceptors in the follicles. This suggests that the
      accuracy of the sea lion's size discrimination was determined by the efficiency
      of two sensory systems: the mechanosensitivity of follicle receptors as well as
      kinaesthesis.

PMID- 7807423
TI  - Looking to the top.

PMID- 7807421
TI  - Purchasing research in the NHS.

PMID- 7807422
TI  - High hopes ...for geriatrics. A view from the top.

PMID- 7807424
TI  - Chiral cognisance: a road to safer and more effective medicinal products.
AB  - A quarter of all synthetic medicinal drugs contain a mixture of equal proportions
      of two molecules that have the same chemical constitution but differ in the
      spatial arrangement of their constituent atoms such that each is a mirror-image
      of the other, like the right and left hand. Biologically, receptors which are
      stereospecific react with only one of the two components of the mixture to
      produce the desired therapeutic effect, while the other is inactive or may
      interact with different receptors to cause undesirable, even toxic, effects.
      Development of syntheses that produce a preponderance of the required form, and
      efficient separation of mixtures, will result in safer and more effective
      medicinal products.

PMID- 7807425
TI  - Knowledge and attitude of nurses on medical wards to defibrillation.
AB  - We questioned 112 qualified nurses working on general medical wards about their
      resuscitation experience and knowledge of ECG interpretation and defibrillation.
      Although all but two of them had been formally trained in basic cardiopulmonary
      resuscitation (CPR) only 16 had received any training in the last six months.
      Seventy-five per cent of nurses were involved in CPR as first responders but only
      18% had used a defibrillator during a cardiac arrest. Identification of ECG
      rhythms and practical knowledge about defibrillation was encouraging despite the
      lack of formal training in this field. Almost every one of the nurses would be
      willing to receive training in advanced cardiac life support. The responses to
      this inquiry suggest that nurses on medical wards are enthusiastic about advanced
      cardiac life support and already have some basic practical knowledge. Appropriate
      training (and retraining) of nursing staff should improve the outcome of
      resuscitation efforts on medical wards.

PMID- 7807426
TI  - Potential impact upon community mortality rates of training citizens in
      cardiopulmonary resuscitation.
AB  - In order to estimate the impact of a community programme of training in
      cardiopulmonary resuscitation (CPR), we reviewed all adult deaths in the city of
      Cardiff (population 292,600) during a 13-week period. Of 701 deaths, 70 were
      cases of fatal out-of-hospital cardiac arrest due to heart disease, for whom it
      was felt that CPR might have been of value. Only 34 (48.6%) deaths were
      witnessed, and in 22 of them the witness did not start CPR. In the majority of
      cases the ambulance service was not summoned immediately. We calculate that a
      community CPR training programme may, at best, reduce the community cardiac
      mortality rate by 7.5%, ie saving between 24 and 56 lives per 100,000 adult
      population per year; but more realistically, such a programme can only achieve a
      reduction of 0.4%, ie saving up to six lives per 100,000 per year. Although
      community CPR training programmes are likely to lead to only a modest reduction
      in community cardiac mortality rates, because countrywide there are many deaths,
      the total of lives saved would be significant. Implementation of such programmes
      should be carefully evaluated.

PMID- 7807427
TI  - Can the elderly tolerate endoscopy without sedation?
AB  - The cardiopulmonary complications associated with gastroscopy could be reduced by
      giving little or no prior sedation. The ability to tolerate the procedure with
      and without sedation was compared in 62 elderly patients by recording responses
      to a questionnaire designed to evaluate the patient's own assessment of the
      examination. A similar percentage of sedated and unsedated patients described the
      procedure as mildly unpleasant (63% vs 57%; chi 2 = 0.500; p > 0.10). The
      majority (73%) of unsedated patients did not want to be sedated for future
      examinations because of the inconvenience of the recovery period. Elderly
      patients should therefore be given the choice of undergoing the procedure without
      sedation. Full counselling and explanation of the procedure are however even more
      important to allay anxiety and apprehension if the procedure is undertaken
      without sedation.

PMID- 7807428
TI  - Endoscopy: throat spray or sedation?
AB  - Anxious patients tolerate endoscopy poorly. It was proposed that such patients
      might derive most benefit from sedation, while most non-anxious patients would
      prefer endoscopy with lignocaine throat spray alone. In a prospective study, 200
      outpatients underwent diagnostic endoscopy after receiving one of two detailed
      information sheets which offered them either the choice between spray or sedation
      (n = 100) or the same choice but encouraged those who were anxious about
      endoscopy to choose sedation (n = 100). When given an informed choice, most non
      anxious patients prefer not to be sedated most non-anxious patients prefer not to
      be sedated during diagnostic endoscopy. If patients who are anxious about the
      procedure are advised to choose sedation, those who nevertheless opt for topical
      throat spray alone find the endoscopy just as comfortable. If the endoscopy were
      to be repeated, 73% of the spray group and 77% of the sedation group would make
      the same choice again. Of 33 patients who chose spray but had been given only
      sedation for a previous endoscopy, 26 (79%) would choose spray again for a future
      endoscopy. The choice of spray or sedation should reflect the patient's view as
      well as that of the endoscopist.

PMID- 7807430
TI  - The Barthel index in clinical practice: use on a rehabilitation ward for elderly
      people.
AB  - Primary activities of daily living (ADL) were monitored weekly in 102 patients
      admitted to a rehabilitation ward for elderly people using the Barthel index. The
      three commonest diagnoses were 'stroke', 'fractured neck of femur' and 'dementia
      recovering from acute illness'. Multiple disabling diagnoses were common: 60% of
      patients had dementia and 23% had a live-in carer; mean (median) length of stay
      in the rehabilitation ward was 98 (62 days). Over 18 months, the weekly
      assessment of patients in the ward was omitted once. No extra resources were
      needed. There was a significant rise in Barthel scores between admission to the
      rehabilitation ward (median Barthel 6) and discharge (median 13) for the group as
      a whole (median change 6, 95% CI 5-7; p < 0.001) and for each of the three main
      diagnostic groups. Barthel scores on discharge were significantly lower than in
      patients discharged from an acute ward for elderly people. Barthel scores and
      mental test scores (MTS) at discharge were significantly related to destination
      on discharge, with a characteristic pattern for patients unable to return home
      and having to be placed in nursing homes (Barthel < 10, MTS < 7). Our experience
      confirms that routine clinical use of the Barthel in this setting is feasible and
      responds to clinically important change, at least in group evaluation. It
      suggests that the Barthel may be useful in outcome measurement, case-mix
      adjustment and audit of discharge practices.

PMID- 7807429
TI  - Integration between general and geriatric medicine: a needs related policy.
AB  - A joint admitting policy between a general physician and a physician in medicine
      for the elderly reduced the length of stay in acute medical beds by 25% without
      increasing the length of stay in rehabilitation beds. The basis for the
      cooperation was not related to age but rather to the perceived needs of the
      patient on admission. This method of integration between medicine and geriatrics
      could be implemented in most hospitals.

PMID- 7807431
TI  - Evolution of a programme of health services research and development in the
      health care of elderly people.

PMID- 7807432
TI  - Measuring outcomes in care of the elderly.
AB  - This observational study was designed to assess whether routine measurement of
      outcomes using standard instruments is possible as part of clinical routine in
      care of the elderly, and to establish if such instruments are responsive to
      clinical change. Indices of functional status, cognitive function and subjective
      health status were collected routinely on admission and discharge in 540
      inpatients and 340 patients attending a day hospital. Data collection became
      integrated into clinical routine. Response rates were generally good and yielded
      acceptably complete data. For inpatients, outcome was reflected by measurement of
      survival, physical function (Barthel index) and social status, each of these
      indicators showing significant change between admission and discharge. For day
      hospital patients, neither these, nor the Nottingham ADL scale, nor a health
      status indicator proved sufficiently responsive to clinical change to merit
      recommendation as outcome indicators for routine use in older patients. In
      ambulatory care in older patients, such as those attending a day hospital, new
      approaches are needed to measure clinical outcomes.

PMID- 7807433
TI  - A visit to Germany. Report of a medicine-Gilliland travelling fellowship.
AB  - Overall the health system in Britain is better and cheaper than that in Germany.
      It is a pity that one needs to go away to appreciate how good our system is. The
      financial problems of the health service in the UK are no different from those in
      Germany except that the cost of the health system in Germany is much greater. The
      training of junior doctors is not as good in Germany as in the UK and
      overspecialisation is introduced too early. There is no supervision or
      counselling of juniors by hospital or college representatives, no vetting of
      posts by college representatives, and professional advancement is often in the
      hands of one consultant. There is evidence of overmanning with widespread
      unemployment amongst doctors in Germany. Geriatric services in Germany have
      little to teach the British except for the concept of the importance of care for
      the elderly which our more acute systems in Britain might have lost. The best
      German rehabilitation centres are excellent and the lucky patients who are in
      such units have better treatment and facilities than those in similar centres in
      Britain. The acute neurological services are most impressive, aggressive and
      intensive but have no follow-up service for patients. Some practices possibly
      create more problems than they solve. There is wide interest in research in
      Germany, with considerable expertise not only in the university but also in
      community hospitals, and a great desire for cooperation with Britain. There are
      many interesting observations and comparisons between the Germany and British
      systems, and each could benefit from incorporating the other's ideas.

PMID- 7807434
TI  - Independent ethical review of studies involving personal medical records. Report
      of a working group to the Royal College of Physicians Committee on Ethical Issues
      in Medicine.
AB  - There is a duty to use available information for the general good where this can
      be done without detriment. It is, in principle, ethically acceptable to use
      personal medical records without approaching or involving the patients concerned,
      provided that confidentiality and anonymity are preserved; such use does not
      require independent ethical approval provided that confidentiality is assured and
      subject to safeguards described below. Epidemiologists have a special interest in
      the use of personal medical records in their work (in this context the use of
      health-related registers and existing biological samples may be included), though
      access to such data involves professional staff in all medical specialties, not
      only those in epidemiology. The following guidance is based on a report of a
      working group (which included non-medical members) to the Royal College of
      Physicians Committee on Ethical Issues in Medicine. Activities such as medical
      audit, epidemiological surveillance, inquiries designed to establish indices of
      morbidity and mortality and outbreak investigations all constitute medical
      practice and as such do not require independent ethical review. Research
      involving access to medical records, health-related registers, or existing
      biological samples only, without direct patient involvement, requires neither
      explicit individual patient consent nor independent ethical review provided that:
      a) explicit consent to access a person's records is obtained either from official
      custodians of the records (who have a duty to satisfy themselves as to the bona
      fides and competence of the investigator) or from the patient's clinician: the
      decision to access personal medical information should not be left to the sole
      discretion of the investigator.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7807435
TI  - Doctors in disasters: their work with the Red Cross and Red Crescent.

PMID- 7807436
TI  - Environmental change and disease. The Lloyd Roberts Lecture 1994.

PMID- 7807437
TI  - Clinical research in the NHS today.
AB  - Most members of the British Medical Research Society who replied to a postal
      questionnaire survey think that clinical research in Britain is in decline.
      Research by NHS staff is being discouraged by hospital managers. Increasing
      service and managerial work by academic and research, staff is curtailing
      research activity. Recruitment of academic physicians is being adversely
      affected. Collaborative research between hospitals and research, made possible by
      tertiary referral, is under increasing threat. This impoverishes the clinical
      service for rare diseases and complex medical and surgical problems. Most
      respondents expect the situation to get worse. Ways must be found to protect
      clinical research before more research teams are irrevocably damaged or broken
      up. Commissioning of some 'new blood' senior lecturers would be the best way to
      improve things, and would greatly raise morale.

PMID- 7807438
TI  - Doctors and the law.
AB  - Many doctors are concerned about the law and the way it relates to their
      professional life, as was evident from the number of delegates attending the
      conference on legal aspects of medicine held at the Royal College of Physicians
      in November 1993. Those taking part came from a diversity of professional
      backgrounds--junior and career grade hospital staff working in various
      specialties, general medical and dental practitioners, prison medical officers
      and police surgeons, specialists in forensic medicine, lawyers and coroners. The
      result was a stimulating exploration of the interface between medicine and the
      law, considering first the doctor's responsibilities in law and the circumstances
      which may lead to an appearance in court, and then the doctor as carer of the
      victims or perpetrators of crime.

PMID- 7807439
TI  - Health care: international comparisons.
AB  - A conference held at the College in July 1994 examined the wide range of health
      care systems employed around the world and their varying responses to the
      combined pressures of demographic change and increasing patient expectations in
      the face of anticipated unsustainable increases in financial demand. The meeting,
      which was planned by Professor Roger Williams, was jointly sponsored by the
      College, the NHS Management Executive, Glaxo Holdings plc, the Nuffield
      Provincial Hospitals Trust and the Kohn Foundation.

PMID- 7807440
TI  - My stroke--mens sana in corpore non sano.

PMID- 7807441
TI  - Anaemia in a blood-donating physician.

PMID- 7807442
TI  - The trouble with ethics committees.

PMID- 7807443
TI  - Is CME really necessary?

PMID- 7807444
TI  - When the earth screamed.

PMID- 7807445
TI  - When the earth screamed.

PMID- 7807446
TI  - Management of acute myocardial infarction.

PMID- 7807448
TI  - Art and literature in the anatomy of Charles Bell.
AB  - The artistic gifts of Sir Charles Bell (1774-1842) directed the course of his
      life's work. There is a fairly extensive literature on the discoveries of Bell in
      neurology and myology but comparatively poorly documented are the ways in which
      Bell exploited his aesthetic talents and erudition to communicate his findings to
      others. This study attempted to answer the question; how did Bell use art and
      literature to teach anatomy? The problem is all the more interesting because, in
      keeping with the spirit of education and improvement of the day, Charles Bell did
      not limit himself to addressing the medical profession but spoke to a wider
      public, dwelling on artists in particular. Bell's oil paintings and drawings, and
      the early editions of his written works, as well as their reviews in the
      contemporary press formed the main source material of this study.

PMID- 7807447
TI  - The MRCP(UK) exam: an examiner's view.

PMID- 7807449
TI  - Audit of major gastrointestinal surgery in patients aged 80 years or over.
AB  - The value of preoperative assessment in relation to outcome and long-term
      survival was studied in 171 octogenarians undergoing major gastrointestinal
      surgery at Dumfries and Galloway Royal Infirmary between 1985 and 1990. The 30
      day mortality rates for elective and emergency operations were 11% and 25%
      respectively. The American Society of Anesthesiologists (ASA) physical status
      scale was found to be a useful predictor of morbidity and mortality. ASA class 2
      patients had a postoperative complication rate of 36% and a mortality rate of 13%
      while the figures for ASA class 4 patients were 85% and 54% respectively. Cox
      proportional hazards survival analysis using the variables age group, sex, ASA
      class, and type of surgery showed that the only statistically significant
      differences were between ASA classes. The relative 5-year survival of 63%
      indicates that these patients compare favourably with a population of the same
      age and sex not undergoing an operation. These data suggest that in the absence
      of severe concomitant medical disease, gastrointestinal surgery can be carried
      out reasonably safely in the elderly.

PMID- 7807450
TI  - A review of burns treated over a one-year period at Mpilo Central Hospital,
      Zimbabwe.
AB  - A retrospective study is presented of 297 patients (57% male and 43% female)
      treated for burns at Mpilo Central Hospital, Bulawayo, Zimbabwe in 1991. Of the
      patients, 73% were in the paediatric age group, 60% of whom were under 5 years of
      age. Most burns occurred at home (90%), with the majority occurring in the
      kitchen (61%). The commonest burning agent was hot water (55%). Open-fire burns
      accounted for 18% of cases. The surface area of burns ranged from 1% to 80% with
      a mean of 7%. The majority of patients (84%) had superficial thickness burns.
      Only 6% of the patients required active resuscitation with intravenous fluids. A
      total of 159 organisms were isolated on 111 pus swabs. The most commonly isolated
      organism was Staphylococcus aureus (66%). Seven patients (five children and two
      adults) died, giving a mortality rate of 2%. Although it is desirable to have a
      purpose-built burns unit this study shows that satisfactory results can be
      achieved with limited facilities. In our practice, where 90% of burns occur in
      the home situation, an active public-education campaign would help to reduce the
      incidence of burns.

PMID- 7807451
TI  - A new incision for intra-oral access without lip split.
AB  - A non-lip-splitting approach to the oral cavity is described, using a curved
      incision through the angle of the mouth along the inferior buccolabial sulcus.
      The incision provides good access to the entire oral cavity and heals efficiently
      with good cosmetic results. It is suited to patients who require excision of the
      oral commissure.

PMID- 7807452
TI  - Constipation and spina bifida occulta: is there an association?
AB  - Spina bifida occulta (SBO) is an abnormality in the posterior arch formation,
      most commonly found at the level of the S1 vertebra. It has recently been
      implicated in the aetiology of urinary voiding problems. We have therefore
      investigated its incidence in female patients with constipation due to outlet
      obstruction (anismus) and slow colonic transit. The plain abdominal radiographs
      of 52 females with constipation, and 48 age-matched controls were reviewed by one
      radiologist, looking for both the incidence of SBO and the incidence of
      abnormally high posterior sacral arc opening (S3 and above) in each group.
      Seventeen (32.6%) patients compared to 11 (22.9%) control subjects had SBO (chi 2
      1.183, P = 0.4). Fourteen (26.9%) patients compared to six (12.4%) control
      subjects had an abnormally high posterior sacral arc opening (chi 2 2.406, P =
      0.2). Three of seven patients (42.6%) with anismus were found to have SBO. Of 19
      patients with slow colonic transit five (26.2%) had SBO and of seven patients
      with a mixed picture, three (42.6%) had SBO. There was no significant difference
      in the incidence of SBO in any of these three patient subgroups when compared to
      the control group. These results suggest that there is no association between
      spina bifida occulta and constipation.

PMID- 7807453
TI  - Surgical correction of Hirschprung's disease: 7 years' experience with the
      Rehbein technique.
AB  - Twenty-seven children with Hirschsprung's disease underwent surgery using a
      modified Rehbein procedure. All the patients were admitted under one unit at the
      Jos University Teaching Hospital, Nigeria, over a 7-year period from April 1985
      to March 1992. There was a male:female ratio of 3:1 with an average age at
      presentation of 21 months. Skin excoriation (19.0%) following initial colostomy
      was the commonest postoperative complication, while wound infection (18.5%)
      featured most often after definitIve surgery. There were no deaths following this
      procedure. The modified Rehbein technique is a safe and efficacious definitive
      method of surgical correction of Hirschsprung's disease.

PMID- 7807454
TI  - Histochemical and metabolic changes in functioning ileal pouches after
      proctocolectomy for familial adenomatous polyposis and ulcerative colitis.
AB  - Ulcerative colitis and familial adenomatous polyposis may be treated by
      proctocolectomy with ileal pouch reconstruction, anastomosing the pouch to the
      anus. We studied 24 patients who underwent this procedure, of whom 12 had
      ulcerative colitis and 12 had familial adenomatous polyposis. Ileal absorption
      was investigated and pouch histology assessed more than one year after closure of
      the protective defunctioning loop ileostomy. The results showed a reduction in
      bile acid reabsorption and vitamin B12 absorption. These observations were
      associated with a morphologic transformation in the small bowel mucosa to large
      bowel mucosa. In 10 of the 12 colitis patients one or more of the histological
      features of the original disease (such as active inflammation, increased
      regeneration, atypia) were evident. Histological examination of the biopsies
      taken from the polyposis patients showed areas with an excess of sialomucins.

PMID- 7807455
TI  - Audit of patients' experiences of cholecystectomy: laparoscopic and open
      operations compared.
AB  - A study was undertaken to compare open cholecystectomy with laparoscopic in terms
      of patient related variables. This was not a randomized study but compared two
      groups of patients treated at different times. A number of variables were
      assessed. The study showed that each method was equally effective in treating
      symptomatic gall stone disease. Very few significant differences, in terms of the
      patients' perceptions of the procedures, were found, although the trend appeared
      to favour the laparoscopic procedure.

PMID- 7807456
TI  - Early definitive operation for bleeding peptic ulcer.
AB  - Thirty-one patients operated on for bleeding peptic ulcer were reviewed. The
      concept was to make an early decision to operate and proceed as soon as the
      patient was haemodynamically stable. In addition to haemostasis, a definitive
      operation was performed. Seventeen general surgeons performed the operations.
      Twenty-four patients (77%) were operated on within the first 24 h. During the
      hospital stay, two deaths (6%) occurred; four patients (13%) re-bled
      postoperatively, all of whom had a second operation. During a mean follow-up of
      45 months, 12 deaths occurred unrelated to peptic ulcer disease and one patient
      had recurrent bleeding. Proximal gastric vagotomy (PGV) was used in 10 of the 14
      duodenal ulcers (71%) without any hospital mortality; one patient re-bled after
      the operation and another during the follow-up. These results support the view
      that early surgery achieves a low hospital mortality and a PGV achieves good
      results even when carried out by several general surgeons.

PMID- 7807457
TI  - Reversal of Hartmann's colostomy.
AB  - From January 1980 to December 1992, sixty-two Hartmann's procedures were
      performed for septic complications of sigmoid diverticular disease, in the
      Professorial Unit at Aberdeen Royal Infirmary. Colorectal continuity was
      subsequently restored in 53% of the fifty-three surviving patients. The overall
      morbidity and mortality was 34% and 0% respectively. There were two anastomotic
      leaks (7%) while two patients (7%) developed anastomotic stenoses requiring
      multiple dilations. Closure of Hartmann's colostomy was carried out by
      consultants (48%), senior registrars (38%) and registrars with consultant
      supervision (14%). Fifteen anastomoses were hand sewn and fourteen were stapled.
      Twenty-one per cent of patients had closure of colostomy in less than 3 months,
      48% between 3 and 6 months and 31% of reversals were carried out more than 6
      months following their formation. The grade of surgeon had no influence on the
      outcome of reversal. Although the numbers were small, the morbidity was found to
      be highest in those patients in whom colostomy closure was carried out within 3
      months of colostomy formation. Also, there was an increased incidence (7%) of
      anastomotic stenoses in the stapled anastomosis group.

PMID- 7807458
TI  - Ascaris cholecystitis and cholangitis: an experience in Myanmar.
AB  - Twenty-seven cases of ascaris cholecystitis and cholangitis were managed in a
      surgical unit of a general hospital in Yangon, Myanmar, from January 1989 to
      March 1990. Nineteen women and eight men with a mean age of 42 years were
      studied. Main clinical manifestations were right hypochondrial pain, fever,
      chills, rigors, nausea, vomiting and jaundice. Diagnosis was established by
      abdominal ultrasonograms in all cases. Laparotomy was performed in all cases
      because of failure to respond to initial conservative treatment. Live and dead
      ascarids were found in the gall bladder and biliary ductal system.
      Cholecystectomy, bile duct exploration, worm extraction and T-tube drainage were
      done in all cases. There were no deaths. Two patients developed minor wound
      sepsis. During the follow-up period ranging from 3 to 12 months, there was no
      recurrence of symptoms in all patients. All patients were given antihelminthics
      before discharge and three weeks later.

PMID- 7807459
TI  - CA 19-9 in carcinoma of the bilharzial bladder.
AB  - Carbohydrate antigen 19-9 (CA 19-9) is a glycoprotein of molecular weight 360,000
      390,000 daltons which is closely related to Lewis blood antigen. It is normally
      secreted by the urothelium and supposed to have a protective function against the
      harmful effect of low pH on the cells. With the development of malignancy its
      secretion increases, secondary to anaerobic glycolysis and lactate accumulation,
      (differentiation trait). It is secreted by the pancreas and may show increase in
      some gastrointestinal malignancies. Carcinoma of the urinary bladder is a major
      problem in Egypt. It represents 26% of malignant tumours, 86% of tumours occur on
      top of bilharzial cystitis. It has three histopathological types: squamous cell
      carcinoma (75.9%), transitional cell carcinoma (TCC) (16%), adenocarcinoma (6%)
      and undifferentiated (2.1%). CA 19-9 serum level was studied in the different
      groups. It was found to be elevated only in TCC. The level was proportional to
      the bulk of malignant tissue and it returned to normal after tumour resection.
      Recurrence was associated with high serum level. CA 19-9 could be of value in
      detection and follow-up of TCC of the bladder.

PMID- 7807460
TI  - The management of splenic injuries in a District General Hospital.
AB  - Between January 1987 and March 1992, 52 patients with splenic injuries were
      treated at Northampton General Hospital. Thirty-nine were men, 13 women with a
      mean age of 30 years (range 5-80 years). Splenic injuries were graded in severity
      from one to five using the organ injury scaling. Fifteen percent were Grade one
      injuries, 33% Grade two, 25% Grade three, 21% Grade four and only 6% Grade five.
      Forty (76%) of injured spleens required splenectomy, 6 (12%) had splenorrhaphy
      performed and 6 (12%) were conservatively treated. In 50% of Grade 1 injuries,
      29% Grade 2 injuries and 23% of Grade 3 injuries the spleen was preserved either
      by nonoperative treatment or by splenorrhaphy. All of Grade 4 and 5 injuries
      required splenectomy. Methods for improving the rate of splenic conservation are
      discussed.

PMID- 7807461
TI  - The risk to the recurrent laryngeal nerves in thyroid and parathyroid surgery.
AB  - The incidence of vocal cord paralysis during operations on the thyroid and
      parathyroid glands in a single surgical unit having a special interest in this
      field has been reviewed over a 9-year period. 97% of all operations were
      reviewed, as were over 98% of nerves at risk, with a minimum follow-up period of
      one year in all cases of paralysis unless normal function was observed earlier.
      The overall rate of paralysis did not differ significantly from previous reports
      but analysis according to the type of goitre and surgical procedure revealed a
      greatly increased risk in retrosternal goitres (17.5%) and in unilateral (11.8%)
      as compared with bilateral resections for nodular goitre (5.2%).

PMID- 7807462
TI  - Survival from non-traumatic clostridial gas gangrene.

PMID- 7807463
TI  - Leiomyomatosis peritonealis disseminata (LPD) with associated endometriosis: a
      case report.

PMID- 7807464
TI  - Radiation scatter during fluoroscopy of extremity fractures.

PMID- 7807465
TI  - Right hemicolectomy and peritoneal lavage in missile injuries of the right colon.

PMID- 7807466
TI  - Accuracy of intraoperative staging in colorectal cancer.

PMID- 7807467
TI  - Accuracy of intraoperative staging in colorectal cancer.

PMID- 7807468
TI  - Preliminary characterization of lymphoid hybridoma cell lines derived from the
      pregnant mouse uterus.
AB  - Seven independent cell lines were derived from the fusion of migratory cells
      recovered from explant cultures of metrial glands to SP 2/0, a non-Ig secreting B
      cell myeloma. The migrating cells came from a pool of metrial glands from day 6-8
      pregnant random bred CD1 mice and were assumed to be cells early in the
      differentiation pathway to granulated metrial gland (GMG) cells. The fused cells
      were cloned twice at the limiting dilution. Hybridization was confirmed by
      quantitation of cellular DNA using propidium iodide staining and by karyotyping.
      Electron microscopy revealed that each of the hybrid cell lines was composed of
      cells which were lymphoid in appearance, but lacked the granules found in mature
      GMG cells. The surface phenotype of all lines is CD45+, LGL-1-, asialo GM-1-, IgG
      , IgM-, CD3- and CD25- (p55 of IL-2 receptor). Although the hybridomas lack those
      phenotypic markers which were used to show that GMG cells are related to the
      natural killer (NK) cell lineage (ie LGL-1, asialo GM-1), they do express the pan
      leukocyte marker CD45 as well as the lytic protein, perforin, at levels
      intermediate to those of SP 2/0 cells and GMG cells. In addition, the hybridomas
      were observed to preferentially bind the NK target cell YAC and to be capable of
      lytic activity at temperatures below 30 degrees C. Because these hybridomas may
      represent fusion to an early progenitor cell of the NK/GMG cell lineage, their
      continued characterization is of merit.

PMID- 7807469
TI  - Correlation of asthenozoospermia with increased antisperm cell-mediated immunity
      in men from infertile couples.
AB  - To investigate whether cell-mediated immunity (CMI) against sperm and/or
      antisperm circulating antibodies are associated with poor semen quality, a
      leukocyte migration inhibition factor (LMIF) assay and an enzyme-linked
      immunosorbent assay (ELISA) were performed in groups of men from infertile
      couples, men from fertile couples and sperm donors. Twenty-five of 102 men (25%)
      revealed positive CMI against sperm and 10 (10%) had positive antisperm antibody
      titers in their sera. Fifteen of 28 asthenozoospermic men (53%) from infertile
      couples revealed positive antisperm CMI. The incidence of antisperm CMI was
      significantly increased (P < 0.05) in the infertile men with asthenozoospermia
      compared with the men from the other two groups (men from fertile couples and
      sperm donors). No significant differences between migration indices were seen
      when such a comparison was done for oligoasthenoterato- and teratozoospermics.
      The results indicate that increased antisperm CMI is associated with
      asthenozoospermia in a significant number of men from infertile couples. The
      importance of these findings is discussed.

PMID- 7807470
TI  - First trimester human trophoblast expresses both interferon-gamma and interferon
      gamma-receptor.
AB  - Interferon-gamma (IFN-gamma) is a lymphokine, produced by activated T
      lymphocytes, which plays a key regulatory role in the host immunological
      responses. In addition, IFN-gamma is expressed by human and porcine trophoblast.
      As IFN-gamma exerts its biological functions through specific cell surface
      receptors and a great number of IFN-gamma receptors (IFN-gamma R) have been
      purified from human placenta, we have examined the relative distribution of IFN
      gamma and IFN-gamma R in human placental tissues at different stages of
      pregnancy. By using immunohistochemical analysis and monoclonal antibodies, it
      was found that IFN-gamma expression is intense in the first trimester but almost
      imperceptible at term, whereas the expression of IFN-gamma R is present at both
      stages of pregnancy. For both lymphokine and receptor, the most intense
      expression was observed in villous syncytiotrophoblast and in extravillous
      interstitial trophoblast. From these results it appears that the expression of
      IFN-gamma R in trophoblast is related to the presence of the lymphokine in the
      early phase of gestation but not later. On this basis, it can be argued that IFN
      gamma exerts its functional role via an autocrine and/or a paracrine loop mainly
      during the first trimester.

PMID- 7807472
TI  - Gestrinone inhibits macrophage function and mitogen-stimulated lymphocyte
      proliferation in vitro.
AB  - Clinical and experimental evidence supports the hypothesis that some steroidal
      drugs with androgenic effects might influence the immune system. The present
      study investigated whether gestrinone is able to affect macrophage and lymphocyte
      activity in vitro. Macrophage function was determined by phagocytosis of
      fluorescent microspheres, whilst lymphocyte proliferation was assessed by cell
      counting. Macrophage phagocytosis was evaluated after an overnight incubation in
      the presence or absence of gestrinone at serial dilutions; lymphocyte
      proliferation was detected in basal conditions and after stimulation with
      Concanavalin A (Con A) in the presence or absence of gestrinone. The results of
      this study showed that gestrinone significantly inhibited macrophage phagocytosis
      at the concentrations of 10(-8), 3 x 10(-8) and 10(-7) M. Furthermore, a
      significant suppression of lymphocyte blastogenesis was observed when lymphocytes
      were incubated with gestrinone at the concentration of 10(-7) M for 6 days. The
      biological significance of gestrinone as an inhibitor of immune functions under
      experimentally defined conditions is discussed in relation to its potential
      mechanism for fertility enhancement.

PMID- 7807471
TI  - Effect of cytokines and anti-adhesion molecule antibodies on the adhesion of
      lymphocytic cells to human syncytiotrophoblast.
AB  - We have previously shown that lymphocytic cells bind to cultured
      syncytiotrophoblast and that this may be important in the lymphocyte-mediated
      infection of trophoblast with the human immunodeficiency virus (HIV). Leukocyte
      trophoblast adhesion may also have implications for normal trophoblast function.
      The following experiments were designed to characterize the adhesion systems that
      mediate the attachment of lymphocytic cells to trophoblast. Adhesion was assayed
      by labelling lymphocytic MOLT-4, clone 8 cells with the fluorescent marker,
      calcein-AM, and then incubating them with primary cultures of human
      syncytiotrophoblast. Adhesion was stimulated by pretreatment of the trophoblast
      cultures with several cytokines either alone or together. These included tumor
      necrosis factor-alpha (TNF-alpha), granulocyte/macrophage-colony stimulating
      factor (GM-CSF), interleukin-1 beta (IL-1 beta) and interferon-gamma (IFN-gamma).
      Stimulation was time- and dose-dependent. In contrast, preincubation of
      trophoblast cultures with anti-TNF-alpha antibodies for 2 days reduced MOLT
      adhesion by almost 50%. Preincubation with other anti-cytokine antibodies had no
      significant effect on adhesion. In other experiments, adhesion was measured in
      the presence of antibodies to known adhesion molecules. Adhesion was reduced by
      50% in the presence of antibodies to alpha 4 integrin or beta 1 integrin. When
      present together, these antibodies reduced adhesion by almost 85%. Incubation in
      the presence of antibodies to the very late activation antigen-4 (VLA-4; alpha 4
      beta 1 integrin) counter-receptors, VCAM-1 and CS-1, was without effect. Adhesion
      was also unaffected by antibodies to LFA-1, ICAM-1, ICAM-2, LFA-2, or LFA-3.
      These results suggest that adhesion is mediated by an adhesion system consisting
      of lymphocyte VLA-4 (alpha 4 beta 1) and an as yet unidentified counter receptor
      on trophoblast.

PMID- 7807473
TI  - Effects of growth hormone and prolactin on testicular macrophages in long-term
      hypophysectomized rats.
AB  - Long-term hypophysectomized (LTHX) rats were treated for 1 week with growth
      hormone (rGH, 600 micrograms/kg body wt.), prolactin (rPRL, 600 micrograms/kg
      body wt.), combined rGH/rPRL or vehicle, to study the effects of these hormones
      on testicular macrophages. Growth hormone and, to a lesser extent, prolactin
      significantly increased the number and size of testicular macrophages. The in
      vivo phagocytic capacity of testicular macrophages was tested by their ability to
      clear the testicular interstitium of dead Leydig cells after treatment with the
      specific cytotoxic reagent ethylene dimethane sulphonate (EDS). In vehicle- or
      rPRL-treated rats, abundant EDS-killed Leydig cells (about 50% of the pre
      existent population) remained in the testicular interstitium 72 h after EDS
      treatment, whereas clearance of the testicular interstitium of dead Leydig cells
      was largely achieved in rGH- or rGH/rPRL-treated rats. These results indicate
      that growth hormone and prolactin have stimulatory effects on testicular
      macrophages in LTHX rats.

PMID- 7807474
TI  - Leuprolide acetate depot for the treatment of uterine leiomyomas. Changes in bone
      density, uterine volume and uterine vascular resistive index.
AB  - This study measured the changes in uterine volume, uterine vascular resistive
      index and lumbar vertebral bone density before and after a six-month course of
      leuprolide acetate depot in women with uterine leiomyomas. All nine patients
      studied were black. The high baseline bone density of black women may provide a
      greater scope for the use of gonadotropin agonists as compared to women in the
      general population. A significant reduction in uterine volume was achieved in the
      patients with leuprolide therapy. Uterine vascular resistive indices were not
      altered consistently following leuprolide therapy in women with leiomyomas.

PMID- 7807475
TI  - Hyaluronic acid membrane for reducing adhesion formation and reformation in the
      rat uterine horn.
AB  - The efficacy of hyaluronic acid (HA) membrane in preventing or reducing
      intraperitoneal adhesion formation and reformation was evaluated in the rat
      uterine horn. Forty-seven Wistar rats were employed. Following a measured laser
      injury on the right uterine horn of each rat, HA membrane was applied to cover
      the site of injury in 20 (HA membrane group). No membrane was applied in another
      20 (control group). The type and extent of adhesions were assessed at
      relaparotomy. Following microsurgical adhesiolysis at second-look laparotomy, the
      same animals were randomized to the HA membrane and control groups. The type and
      extent of adhesion reformation were evaluated at third-look laparotomy. Following
      a similar injury on the right uterine horn in another seven rats, HA membrane was
      applied on both uterine horns. A repeat laparotomy was performed three hours
      later to assess the status of the membrane. The type and extent of adhesion
      formation and reformation were comparable between the HA membrane and control
      groups. The HA membrane did not remain on the uterine horn and gelled rapidly.
      Hyaluronic acid membrane was ineffective in reducing adhesion formation and
      reformation in the rat uterine horn.

PMID- 7807476
TI  - Microinvasive squamous cell carcinoma of the cervix.
AB  - The International Federation of Gynecologists and Obstetricians (FIGO) definition
      of microinvasive carcinoma of the cervix changed recently. We clinically reviewed
      our treatment of superficially invasive cancer of the cervix in light of those
      changes. The review covered all patients treated at the University of Michigan
      from 1970 to 1985 who had stage I squamous cell carcinoma of the cervix, with the
      Society of Gynecologic Oncologists (SGO) and new FIGO criteria for microinvasion
      used. Using SGO criteria, 43 patients were treated as follows: total abdominal
      hysterectomy (32), total vaginal hysterectomy (7), radical hysterectomy (2) and
      cone biopsy (2). One patient, who had multifocal disease with a maximum depth of
      1.5 mm, developed a recurrence and died of the disease. A review of 345 patients
      considered to have stage IB disease under SGO criteria showed 30 patients who
      were reclassified as having stage IA2. All these patients were treated with
      radical surgery and survived, and all had negative lymph nodes. Radical surgery
      for patients with more than microinvasion according to SGO criteria provides
      excellent survival rates. Radical therapy may also be indicated for multifocal
      lesions.

PMID- 7807477
TI  - Diagnostic pitfalls of ultrasonographic uterine screening in women treated with
      tamoxifen.
AB  - Recent reports of an association between tamoxifen treatment for breast cancer
      and endometrial pathology prompted a screening program for women receiving
      tamoxifen. Twenty-two women were examined; 15 were asymptomatic, and 7 were
      referred because of abnormal vaginal bleeding. All underwent vaginal
      ultrasonography followed by endometrial sampling. The sonographic studies showed
      endometrial abnormalities in all 22 women--typically, irregular thickening of the
      endometrium. Some had cystic formations, and three had fluid in the endometrial
      cavity. No pathology or inadequate material was found in the endometrial samples
      from the 15 asymptomatic women. Endometrial polyps were suspected sonographically
      and removed from two of the five women with vaginal bleeding. The discrepancy
      between the sonographic findings and histology in the asymptomatic women could
      have been due to stromal edema from tamoxifen treatment. Abnormal
      ultrasonographic findings in asymptomatic women treated with tamoxifen probably
      represent insignificant changes in the endometrial architecture and not a true
      abnormality. The need for routine endometrial sampling or hysteroscopy in every
      case is therefore questionable.

PMID- 7807478
TI  - Detection and measurement of thyroid stimulating hormone in human follicular
      fluid.
AB  - The objectives were to measure thyroid stimulating hormone (TSH) levels in human
      follicular fluid (FF) and compare them with serum levels. Serum and FF samples
      were obtained from women (n = 41) undergoing in vitro fertilization/embryo
      transfer, gamete intrafallopian transfer and zygote intrafallopian transfer.
      Ovulation induction was achieved using human menopausal gonadotropins and human
      chorionic gonadotropin (hCG) after pituitary suppression with a gonadotropin
      releasing hormone agonist. Blood samples obtained on the day of hCG injections
      were assayed for TSH. Follicular fluids were obtained at the time of oocyte
      retrieval (approximately 34 hours after hCG injection). Serum and FF TSH levels
      were measured using an enzyme immunoassay. The correlation between serum and FF
      TSH levels was determined. Comparison between mean serum and FF levels was done
      using Student's t test after logarithmic transformation of the data. Levels of
      TSH in FF (1.71 +/- 0.14 microIU/mL, mean +/- SEM) were not different (P > .05)
      from levels in serum (1.43 +/- 0.10). Serum and FF levels correlated positively
      (r = .7). TSH appears to be present in human FF, and the levels in FF are similar
      to those in serum.

PMID- 7807479
TI  - Evaluation of the atypical cytologic smear. Validity of the 1991 Bethesda System.
AB  - The 1991 Bethesda System states that atypical squamous or glandular cells of
      undetermined significance should be further classified as reactive or
      premalignant/malignant. The validity of this qualification for identification of
      patients with cervical intraepithelial neoplasia (CIN) was tested. One hundred
      twenty-four cytologic smears with squamous atypia were reviewed retrospectively
      by two cytopathologists blind to the colposcopy results. The smears were
      classified as favoring either reactive or premalignant/malignant processes.
      Subjective criteria used in the classification were based on the pathologists'
      experience. All patients underwent colposcopy and selected biopsy under the
      direction of a gynecologic oncologist. Of the 124 atypical smears, 69 were
      classified as favoring reactive processes and 55 as favoring
      premalignant/malignant processes by cytopathologist 1. Cytopathologist 2
      classified 68 as reactive and 56 as premalignant/malignant. Colposcopy and
      selected biopsy revealed the following lesions: 34 cases of human papillomavirus
      (27.4%), 17 of CIN 1 (13.7%), 4 of CIN 2 (3.2%), 2 of CIN 3 (1.6%) and 67 without
      pathology (54.0%). All six patients with squamous atypia and underlying CIN 2 and
      3 lesions had their cytology classified as premalignant/malignant by the
      cytopathologists. In these patients this qualification had high sensitivity
      (100%) and negative predictive value (100%). The 1991 Bethesda System
      classification above, when applied to patients with squamous atypia, was
      effective in identifying patients with serious pathologic cervical lesions. If
      used as a triage method, colposcopy should be reserved for atypical lesions
      classified as premalignant/malignant, potentially decreasing the cost of health
      care without decreasing the quality of that care.

PMID- 7807480
TI  - Transcranial assessment of maternal cerebral blood flow velocity in normal vs.
      hypertensive states. Variations with maternal posture.
AB  - This study compared the effect of a change in maternal posture on maternal
      cerebral blood flow velocity assessed transcranially in normal vs. various
      hypertensive groups. Ten normotensive, 10 preeclamptic and 10 chronically
      hypertensive patients had maternal middle cerebral artery (MCA) blood flow
      velocity assessed in three positions--left lateral decubitus, supine and sitting
      upright--using 2-mHz transcranial Doppler ultrasound. Comparison was then made of
      the effect of a change in posture on cerebral blood flow velocity in each group
      using analysis of variance with Student's t test for statistical significance.
      Normotensive and chronically hypertensive women showed minimal changes in MCA
      blood flow velocity, while preeclamptic women showed a 30% rise in all aspects of
      MCA blood flow velocity from the left lateral decubitus to sitting up. In
      preeclamptic women, MCA blood flow velocity, which showed a significant rise with
      changes in posture, was not accompanied by significant changes in blood pressure
      and so is not a secondary response to a change in cardiac output but may be a
      primary effect of local circulatory changes.

PMID- 7807481
TI  - Ultrasonographic growth and Doppler hemodynamic evaluation of fetuses of obese
      women.
AB  - All fetuses benefit from ultrasonographic estimation of gestational age and
      evaluation of growth patterns. Monitoring the pregnancies of obese women is
      perceived as more difficult than monitoring those of nonobese women. The aim of
      this study was to determine if maternal obesity affects the growth and Doppler
      resistance indices (RI) of the fetus. Twenty-eight women with a preconception
      weight > 90.7 kg underwent obstetric ultrasonographic evaluations from the 20th
      week of gestation. Their ultrasonographic data were compared with those of
      controls. Ten of the obese women developed gestational diabetes and had lower
      umbilical artery RIs for a given gestational age (P < .0001) than did those obese
      women without other medical complications, those with medically controlled
      pregnancy-induced hypertension or those from the control population. The relation
      between fetal unit weight and umbilical artery RIs was established. The pattern
      of RI changes was similar in all groups when estimated fetal weight instead of
      gestational age was used as the covariant. Fetal growth and Doppler velocimetry
      can be monitored adequately in obese women. Gestational diabetes significantly
      influences the pattern of fetal growth and the impedance to flow in the umbilical
      artery.

PMID- 7807482
TI  - In vitro fertilization and embryo transfer. A historical perspective.

PMID- 7807483
TI  - Family views on sterilization for their mentally retarded children.
AB  - Eighty-eight parents of adolescents or adults with mental retardation answered
      written and/or telephone questionnaires concerning sterilization and reproductive
      health choices for their children with mental retardation. The 36 parents whose
      children were still living at home were more concerned about the capacity for
      sexual activity in their disabled child than were the 52 parents whose children
      were living outside the home. Otherwise, the two groups of parents were very
      similar in their attitudes. The reasons for considering sterilization were
      parental fear of sexual abuse, unwanted pregnancy and failure of birth control
      methods. Almost all the parents in this study wanted to participate in decisions
      concerning the sterilization of their disabled child.

PMID- 7807484
TI  - Post-cesarean section febrile morbidity. Antibiotic prophylaxis in low-risk
      patients.
AB  - A study was conducted to assess whether antibiotic prophylaxis in low-risk
      patients for post-cesarean febrile morbidity was beneficial and cost effective.
      In a randomized, prospective study, 167 patients received a single, 1-g dose of
      cefazolin before clamping of the cord, and 140 did not. In the group given
      prophylaxis the febrile morbidity and postoperative therapeutic antibiotic usage
      were significantly lower than in the group not given prophylaxis (9% vs. 17.9%, P
      = .035, and 6.5% vs. 20%, P < .001, respectively). We conclude that single-dose
      cefazolin prophylaxis is both beneficial and cost effective, even in patients
      considered to be at low risk of post-cesarean febrile morbidity. Since the value
      of antibiotic prophylaxis in high-risk patients is accepted, universal antibiotic
      prophylaxis in every cesarean section case is suggested.

PMID- 7807485
TI  - Effects of coping style on psychological reactions of low-income, minority women
      to colposcopy.
AB  - Patterns of coping and adjustment in 36 low-income, minority women with positive
      cytologic smears were assessed prior to diagnostic follow-up examination
      (colposcopy). Subjects were divided into high monitors (who attend to threatening
      cues) and low monitors (who avoid threatening cues) on the basis of their scores
      on the Miller Behavioral Style Scale, a well-validated measure of coping style.
      Multivariate analysis of variance showed that high monitors worried more about
      the seriousness of their condition, expressed more concern about the immediate
      sensory and procedural aspects of the diagnostic examination and felt more
      responsible for the onset and course of their disease as compared to low
      monitors. However, they were no more likely to be concerned about the overall
      importance or long-term consequences of their abnormal smears. Finally, high
      monitors displayed greater symptoms of intrusive and avoidant ideation in
      relation to their medical status. These results were independent of
      sociodemographic and medical confounding variables. Consistent with results in
      other populations, the findings suggest that it may be useful to assess
      attentional coping dispositions in minority populations with high-risk
      gynecologic conditions and to target psychosocial interventions accordingly.

PMID- 7807486
TI  - Lipoprotein alterations from a triphasic oral contraceptive containing ethinyl
      estradiol and gestodene. A 12-month trial.
AB  - To evaluate the lipid and lipoprotein changes induced by a triphasic oral
      contraceptive (OC) containing ethinyl estradiol and gestodene, 25 healthy women
      from the Baltimore metropolitan area were enrolled in an open-label,
      noncomparative study. Serum lipids were measured prior to starting the OCs and
      again during the 3rd, 6th and 12th treatment cycles. Mean lipid concentrations in
      each treatment cycle were compared to baseline levels using the t test for paired
      samples. Small but statistically significant (P < or = .05) increases in the mean
      concentrations of total cholesterol, total triglycerides, total high density
      lipoprotein (HDL) cholesterol, HDL3 cholesterol, apolipoprotein A1 and
      apolipoprotein B were noted. Although the increases were statistically
      significant, the mean lipid concentrations were still within the normal range.
      The mean HDL2 and low density lipoprotein cholesterol concentrations were
      unchanged, as was the mean total cholesterol/HDL ratio. Healthy women taking a
      triphasic OC containing ethinyl estradiol and gestodene have minimal changes in
      lipids and should not be at increased risk of atherosclerosis due to OC-induced
      lipid alterations.

PMID- 7807487
TI  - Copper in split and daily ejaculates.
AB  - The authors studied the copper level in three splits of 21 ejaculates to locate
      the origin of copper in semen. The copper level was rich in the first split and
      poor in the second. The results indicated that copper is released from all
      portions of the genital tract and that the major share is from the prostate
      gland. Another group of 26 volunteers submitted their semen samples once a day
      for 10 days for a study of the role of copper in fertility. A gradual increase in
      sperm motility was observed from the first day. There was no consistency in the
      level of copper in this study, and it did not correlate with any of the semen
      parameters studied.

PMID- 7807488
TI  - Pregnancy after unilateral oophorectomy in a woman with hyperthecosis ovarii. A
      case report.
AB  - Ovarian hyperthecosis has been described exclusively as bilateral. It occurs
      predominantly in perimenopausal women but may be seen at any age after puberty.
      In a young woman, stromal hyperthecosis is characterized by virilism, menstrual
      disorders and infertility. Ovarian suppression therapy, induction of ovulation
      and wedge resection of the ovaries have been ineffective, and only bilateral
      oophorectomy has caused regression of virilism in these patients. Conservative
      surgery in appropriate cases may save many young women desiring pregnancy from
      having bilateral oophorectomy. This case report describes a unique situation in
      which a young woman with ovarian hyperthecosis achieved three pregnancies after
      unilateral oophorectomy, indicating the possibility of unilateral ovarian
      hyperthecosis in our patient.

PMID- 7807489
TI  - Intentional delay of aftercoming siblings. A report of two cases.
AB  - Intentional delay of the birth of the aftercoming sibling or siblings in multiple
      gestations is uncommon. Our experience with two such cases is reported.

PMID- 7807490
TI  - Hypothalamic atrophy presenting as amenorrhea and sexual infantilism in a female
      adolescent. A case report.
AB  - A 17-year-old girl presented with amenorrhea, sexual immaturity and a remote
      history of head trauma. Provocative testing of the pituitary with thyrotropin
      releasing hormone, gonadotropin releasing hormone and insulin-induced
      hypoglycemia revealed intact pituitary function, with hypothalamic insufficiency.
      Furthermore, magnetic resonance imaging of the brain demonstrated loss of the
      hypothalamic infundibulum. To our knowledge, these structural defects have not
      been found with magnetic resonance imaging in cases of hypothalamic atrophy. This
      case suggests that the infundibulum or pituitary stalk may be vulnerable to
      traumatic damage, leading to hypothalamic insufficiency persisting into
      adulthood.

PMID- 7807491
TI  - Endometrial ablation for life-threatening abnormal uterine bleeding. A report of
      two cases.

PMID- 7807492
TI  - Ureteral injury during elective pregnancy termination. A case report.
AB  - This case is the sixth reported one of ureteral injury following elective
      pregnancy termination. It reemphasizes that the anatomic relationship of the
      ureter to the lower genital tract can predispose to surgical injury.

PMID- 7807493
TI  - Neisseria meningitidis sepsis as a complication of labor. A case report.
AB  - Bacteremia in the obstetric patient is an uncommon event. The occurrence of
      sepsis is even more rare. We report a case of maternal sepsis complicating labor
      and delivery in which the blood culture isolate was Neisseria meningitidis.

PMID- 7807494
TI  - Acute pelvic inflammatory disease after tubal sterilization. A report of three
      cases.
AB  - Pelvic inflammatory disease (PID) is considered to be rare or nonexistent
      following tubal sterilization. The purpose of this report is to describe three
      cases of surgically diagnosed acute PID in women previously sterilized by
      bilateral tubal ligation who presented over a one-year period. All three patients
      presented with an acute abdomen, fever and elevated white blood cell count. Our
      experience suggests that PID following tubal sterilization is more common than
      previously described and can present a diagnostic dilemma.

PMID- 7807495
TI  - Accuracy of the Omron HEM 706 portable monitor for home measurement of blood
      pressure.
AB  - A reliable, well-validated home blood pressure (BP) self-measurement device could
      have an important role in the management of hypertension by the early
      identification of 'white coat' hypertensives. Under rigorous assessment such
      devices have not performed well in the estimation of DBP, particularly in the
      hypertensive range. We assessed the Omron HEM 706 device (oscillometric) for home
      measurement of BP according to the standards set out by the British Hypertension
      Society protocol and the Association for the Advancement of Medical
      Instrumentation (AAMI). The device was compared with simultaneous measurements
      made by two 'blinded' observers using a standard mercury sphygmomanometer in the
      same arm in 85 subjects aged 17-76 years with a wide range of BPs. The device was
      satisfactory over the whole BP range (SBP 89-188 mmHg, DBP 44-118 mmHg), with a B
      grading for SBP and a C grading for DBP (British Hypertension Society protocol)
      and a PASS for both SBP and DBP (AAMI). For the diastolic hypertensive range 90
      120 mmHg, where most clinical decisions are made, the device scored a B grade for
      SBP and an A grade for DBP, with a PASS for both SBP and DBP. We conclude the
      Omron HEM 706 device for home BP measurement is highly satisfactory, particularly
      in the mild to moderate hypertension range, and is suitable for clinical use.

PMID- 7807496
TI  - The what, why and how of hypertensive heart disease.
AB  - Left ventricular hypertrophy is now recognised to be an important risk factor
      associated with such adverse cardiovascular events as myocardial infarction,
      heart failure, stroke and sudden cardiac death. This is true for the general
      population and those with uncomplicated hypertension. Herein the what, why and
      how of hypertensive heart disease (HHD) is reviewed: what is it, why does a
      structural remodelling of the myocardium occur and how can it be prevented on the
      one hand or regressed on the other. Clinical and experimental studies are
      presented to address each of these issues.

PMID- 7807498
TI  - Lack of association between the I/D polymorphism of the angiotensin-converting
      enzyme gene and essential hypertension in a Belgian population.
AB  - We tested the insertion/deletion (I/D) polymorphism of the ACE gene in 119
      hypertensive patients and in 109 normotensive controls by means of the polymerase
      chain reaction (PCR). The allele and genotype frequencies of the I/D polymorphism
      in the ACE gene are essentially identical in both groups, regardless of age or
      sex. The I/D polymorphism of the ACE gene is thus not implicated in Belgian
      hypertensive patients.

PMID- 7807497
TI  - Serum uric acid and hypertension: the Olivetti heart study.
AB  - The association between serum uric acid and hypertension was evaluated in a
      sample of male workers in southern Italy enrolled in the Olivetti Heart Study, an
      ongoing longitudinal epidemiological investigation on risk factors for coronary
      heart disease carried out at the Olivetti factory in the suburban area of Naples.
      Participants were screened at baseline (1975) and at five year (1980) and 12 year
      (1987) follow-up examinations. The present report focuses on 619 male workers for
      whom information on coronary heart disease risk factors was available both at
      baseline and 12 year follow-up examination. At baseline, after excluding
      hypertensive participants (systolic blood pressure (SBP) > or = 140 mmHg and/or
      diastolic blood pressure (DBP), > or = 90 mmHg and/or on antihypertensive
      therapy; n = 72), serum uric acid was positively and significantly related to
      age, SBP, DBP, body mass index (BMI), serum total cholesterol (CHOL) and serum
      triglycerides (TG) in 547 normotensive participants. At 12 year follow-up
      examination, hypertension was defined by SBP > or = 140 mmHg and/or DBP > or = 90
      mmHg and/or being on antihypertensive therapy. Multiple logistic regression
      analysis showed an independent positive association between serum uric acid
      levels and development of hypertension (RR = 1.23, 95% CI = 1.07-1.39; p = 0.011)
      after adjustment for age, BMI, CHOL and TG. Furthermore, according to more severe
      degrees of hypertension (SBP > or = 160 mmHg and/or DBP > or = 95 mmHg and/or
      being on antihypertensive therapy), the relative risk to develop hypertension was
      still significant (RR = 1.19; CI = 1.01-1.38; p = 0.051).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7807499
TI  - Association between ACE-D/D polymorphism and hypertension in type II diabetic
      subjects.
AB  - The ACE gene has recently been shown to be associated with myocardial infarction,
      especially in subjects considered at low risk for coronary heart disease (CHD)
      according to common classification criteria. The possible relationship between
      deletion polymorphism in this gene and CHD risk factors, as well as asymptomatic
      extracoronary atherosclerosis, has been investigated in the present study. One
      hundred and seventy-four subjects, enrolled in a cardiovascular disease
      prevention study, underwent clinical and biochemical examination and ACE-I/D
      polymorphism determination. Subjects > 45 years of age (n = 107) also received
      echo-Doppler examination of the carotid arteries. Based on the results of ACE-I/D
      polymorphism, subjects were divided into three groups: homozygous for deletion
      (D/D), homozygous for insertion (I/I) and heterozygous (I/D). The prevalence of
      CHD risk factors as well as of extracoronary atherosclerosis was similar in the
      three genotype groups. Similarly, there was no association between the presence
      of atherosclerotic lesions and genotype in subjects at low and high CHD risk. Ten
      subjects with diabetes mellitus had ACE-D/D genotype. Among these subjects seven
      had hypertension. Eight subjects with diabetes mellitus had ACE-I/D genotype and
      only one of these was hypertensive. None of the ACE-I/I subjects was diabetic.
      ACE-I/D polymorphism seems to play a role in the development of hypertension, at
      least in diabetic subjects. Its determination may help to identify and monitor
      diabetic subjects prone to hypertension.

PMID- 7807500
TI  - Abnormalities of rheology and coagulation in hypertension.
AB  - While the arterial tree is exposed to increased pressure flow, paradoxically the
      complications of hypertension are mainly thrombotic rather than haemorrhage.
      Improved techniques have allowed the identification of haemorrheological indices,
      coagulation factors and markers of arteriolar endothelial and platelet
      dysfunction which potentially contribute to thrombus formation (thrombogenesis)
      in patients with hypertension. These factors may be important in the
      pathogenesis, complications and prognosis of such patients. The purpose of this
      review is to examine the complex relationship between hypertension and blood
      rheology, platelets and related components of the coagulation system.

PMID- 7807501
TI  - Diastolic pressure as an index of salt sensitivity.
AB  - This paper analyses the association between blood pressure and sodium excretion
      in 3975 individuals aged 20-74 years, selected in a probability sample survey of
      private households carried out in Rio Grande do Sul, Brazil. Sodium and
      creatinine titrations were performed in casual urine samples collected at the
      time of BP measurements. A subsample of 611 subjects provided 24 h urine
      collections. The regression slopes of systolic pressure on sodium excretion
      increased when diastolic level was higher. At the lowest levels of diastolic
      pressure the slope did not differ significantly from zero. The adjusted
      correlation coefficient then rose progressively to a maximum of +0.41 at
      diastolic pressures of 95-99 mmHg. Strikingly, at diastolic pressures of > or =
      100 mmHg, there was no longer any significant association between systolic
      pressure and sodium excretion. These results could explain some earlier
      contradictory findings concerning the role of salt intake in hypertension and
      provide estimates of expected reduction on the prevalence of hypertension in each
      diastolic pressure group following a reduction on salt intake of a population.

PMID- 7807502
TI  - Clinic and 24h blood pressure in elderly treated hypertensives with postural
      hypotension.
AB  - The objectives of this study were to determine the prevalence of, and factors
      associated with, postural hypotension (PH) in elderly treated hypertensive
      subjects, to examine the 24h BP profile in those subjects with and without PH and
      to determine the effects of antihypertensive treatment withdrawal on the
      prevalence and symptoms of PH. Eighty-six subjects (mean age +/- standard
      deviation 76 +/- 6 years) on antihypertensive drug therapy for > 6 months had
      three clinic BP measurements taken in supine and standing positions followed by
      24h ambulatory BP monitoring. Forty-seven subjects underwent repeat BP
      measurement five weeks after withdrawal of antihypertensive medication and
      institution of standard nonpharmacological methods. Twenty-six (30%) of the 86
      subjects exhibited PH (defined as SBP fall on standing > or = 20 mmHg) within
      three minutes of standing. Supine clinic and 24h SBP and DBP, age and presence of
      previous cardiovascular events were similar in the groups with and without PH.
      There was a significant correlation between the orthostatic BP fall for all
      subjects and day-night SBP difference (r = -0.30, P = 0.01) and urinary
      sodium:creatinine ratio (r = -0.33, P = 0.04). Multiple regression analysis
      revealed only the day-night SBP difference was a significant predictor of
      orthostatic BP change. In the PH group, 19 subjects had treatment withdrawn
      resulting in a reduction of 58% (P > 0.001) in those continuing to demonstrate
      PH. If indicated a trial of antihypertensive drug treatment withdrawal could
      reduce the risk of PH; the additional benefit of instituting nonpharmacological
      therapy in reducing BP and orthostatic hypotension warrants further assessment.

PMID- 7807503
TI  - Reduced urinary kallikrein excretion in human renovascular hypertension caused by
      nonspecific aortoarteritis and other disorders.
AB  - In this study urinary kallikrein excretion was measured using the kininogenase
      bioassay technique in 12 normal volunteers and 23 patients with angiographically
      proven renovascular hypertension (RVHT). In 13 of these (group I), RVHT was due
      to nonspecific aortoarteritis (NSAA) and in 10 (group II) due to other causes.
      Urinary kallikrein (UKa) excretion was significantly lower in patients, with
      values still lower in NSAA. PRA was high in both the groups in comparison with
      controls; however, the levels were significantly lower in group I compared with
      group II. Finding of both UKa and PRA lower in group I is suggestive of long
      standing hypertension becoming volume dependent with nephrosclerotic changes in
      the kidney. These results point to decreased renal kallikrein-kinin system
      activity as a feature of NSAA that probably contributes chiefly to the
      maintenance of the hypertensive state. Normalisation of BP with restoration of
      UKa and PRA towards normal in three patients of group I and five in group II
      further support the role of UKa not only when over activity of renin-angiotensin
      system is responsible for RVHT as in group II but also in group I when the
      hypertension becomes volume dependent.

PMID- 7807504
TI  - Speed and duration of dose titration with the angiotensin converting enzyme
      inhibitor quinapril: relationship with efficacy in patients with moderate
      hypertension.
AB  - Most antihypertensive agents, including ACE inhibitors, are routinely dose
      titrated upwards every two weeks in both clinical trials and clinical practice to
      achieve control of systemic pressure. Two separate clinical trials assessing
      comparative antihypertensive efficacy of quinapril versus other ACE inhibitors
      (enalapril and captopril) were conducted in a double-blind fashion in patients
      with moderate to severe hypertension already receiving a diuretic (study I: entry
      DBP > or = 105 and < or = 120 mmHg while taking 25 mg hydrochlorothiazide; study
      II: DBP > or = 110 and < or = 130 mmHg while taking 25 mg chlorthalidone). In
      study I, 88 patients were randomised to receive quinapril (10-40 mg twice daily)
      which was titrated upwards every one to two weeks as necessary to reduce DBP < or
      = 90 mmHg (titration period six weeks, followed by an additional six weeks of
      therapy during which open-labelled beta-blocker therapy could be added for
      nonresponders). In study II, 84 patients were randomised to receive quinapril (5
      20 mg twice daily) which was titrated upwards every four weeks as necessary to
      reduce DBP < or = 90 mmHg (titration period 16 weeks, followed by a 12-week
      maintenance period). Both cohorts of patients were demographically slightly
      dissimilar because there were more females and higher baseline DBP in study II
      versus study I (60% vs 34%, and 115.0 vs 109.1 mmHg, respectively) and more
      blacks (26% vs. 0%) and heavier patients (90 kg vs. 73 kg) in study I versus
      study II.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7807505
TI  - Bisoprolol-induced nightmares.

PMID- 7807506
TI  - Screening of a population of young hypertensives for primary hyperaldosteronism.

PMID- 7807507
TI  - Introduction: actions of ACE inhibitors in hypertension--broader than blood
      pressure control.

PMID- 7807508
TI  - Hypertrophy to failure.
AB  - Left ventricular hypertrophy (LVH) is a common consequence of hypertension, and
      an independent risk factor for cardiovascular morbidity and mortality. The
      presence and severity of LVH is best determined by echocardiography and expressed
      as left ventricular mass index or left ventricular wall thickness. Pathological
      LVH, in response to pressure or volume load on the heart, is characterised by
      myocyte hypertrophy and hypertrophy/hyperplasia of nonmyocyte cells within the
      myocardium. Angiotensin II and aldosterone are promoters of increased fibroblast
      activity and a significant increase in collagen fibres in the myocardium. Early
      diagnosis and treatment of hypertension has significantly decreased the incidence
      of LVH and subsequent heart failure in many countries, but the choice of
      antihypertensive therapy alters the rate of reversal of LVH and the subsequent
      development of heart failure. Angiotensin converting enzyme (ACE) inhibitors,
      beta-blockers and calcium channel blockers produce the most rapid reversal of
      hypertrophy. Meta-analysis of these many small trials suggests an advantage of
      ACE inhibitors over other groups of antihypertensive agents.

PMID- 7807509
TI  - Insulin-like growth factor I and collagen type III synthesis in patients with
      essential hypertension and left ventricular hypertrophy.
AB  - An excess of circulating insulin-like growth factor I (IGF-I) has been found in
      patients with essential hypertension and left ventricular hypertrophy (LVH). In
      addition, an increase in collagen type III synthesis has also been reported in
      hypertensive patients. Since IGF-I is a positive effector of collagen type III
      expression, we have investigated whether a relationship exists between
      circulating IGF-I and collagen type III synthesis in patients with essential
      hypertension. The relationship between plasma concentrations of IGF-I and an
      index of tissue synthesis of collagen type III (serum concentrations of
      procollagen type III aminoterminal peptide [PIIIP]) was investigated in 37
      patients with essential hypertension before and after six months of treatment
      with lisinopril. The control group consisted of 30 age- and sex-matched
      normotensive subjects without LVH. Baseline concentrations of IGF-I were higher
      in hypertensive patients than in normotensive controls (285 +/- 25 vs. 240 +/- 15
      ng/ml; P < 0.01). Mean IGF-I levels were higher in hypertensive patients with LVH
      (n = 10, 330 +/- 49 ng/ml) than in those without LVH (n = 27, 252 +/- 25 ng/ml; P
      < 0.05). Baseline concentrations of PIIIP were higher in hypertensive patients
      than in normotensive controls (10.07 +/- 0.54 vs. 8.47 +/- 0.77 ng/ml; P < 0.01).
      Mean PIIIP levels were higher in hypertensives with LVH than in those without LVH
      (12.20 +/- 0.78 vs. 7.97 +/- 0.55 ng/ml; P < 0.05). There was no correlation
      between IGF-I and PIIIP at baseline.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7807510
TI  - Quality of life in hypertension.
AB  - Mild to moderate hypertension is usually asymptomatic and therefore the impact on
      quality of life and side-effects of the antihypertensive treatment can have a
      negative effect on treatment compliance. A number of comparative studies have
      addressed quality of life issues with various antihypertensive agents, and the
      results of these studies are summarised in this article with particular reference
      to ACE inhibitors.

PMID- 7807511
TI  - Beyond blood pressure.
AB  - The majority of deaths attributable to increased blood pressure are due to
      coronary heart disease (CHD) and, consequently, the prevention of CHD should be
      the primary aim of hypertension management. It is clearly established that CHD
      has a multifactorial aetiology. As such, optimal hypertension management should
      include evaluation and management of all concomitant risk factors found in
      hypertensives. Data have shown that the newer agents such as ACE inhibitors,
      calcium antagonists and alpha-blockers have favourable effects on serum lipids,
      glucose intolerance, hyperinsulinaemia and left ventricular hypertrophy and, as
      such, are more likely to provide protection against coronary morbidity and
      mortality than diuretics and beta-blockers. While we do not have any long-term
      morbidity and mortality trial evidence to confirm or refute the potential
      benefits of these newer agents, such data are likely to be available in several
      years' time. In the meantime the practising physician has to make a best estimate
      as to what may be optimal therapy for hypertensive patients.

PMID- 7807512
TI  - Mortality matters.
AB  - When treating cardiovascular disorders such as arterial hypertension, the major
      goal of treatment is to reduce morbidity and mortality. The present review will
      concentrate on how the treatment of cardiovascular disorders affects mortality.
      Hypertension studies performed in the 1950s showed that treatment of malignant
      hypertension improved five year survival dramatically. More recent studies in
      patients with nonmalignant hypertension have shown positive effects on mortality
      as well, especially with regard to the treatment of hypertension in the elderly.
      Other cardiovascular disorders have also been treated successfully with regard to
      mortality. This is true in particular of postmyocardial infarction patients, in
      whom beta-blocker treatment has been effective. Moreover, patients with
      congestive heart failure have been shown to benefit from treatment with
      angiotensin converting enzyme (ACE) inhibitors as regards total mortality. The
      most recent addition to our knowledge stems from the GISSI-3 trials in which
      lisinopril, alone or in combination with nitrates, was shown to reduce mortality
      in patients with acute myocardial infarction.

PMID- 7807513
TI  - Arterial stiffening and vascular/ventricular interaction.
AB  - Arterial stiffness is the major determinant of systolic pressure and increases
      with age and hypertension, especially in the thoracic aorta and major central
      elastic arteries. The effects of arterial stiffening on aortic and left
      ventricular systolic pressure are underestimated when taken from conventional
      recordings of systolic pressure in the brachial artery or in other arteries of
      the upper limb, as a consequence of pressure wave transmission in the upper limb.
      A method has been devised to synthesise the ascending aortic pressure wave from
      the radial or brachial artery pressure wave, as measured invasively by arterial
      cannula or noninvasively by applanation tonometry. Results obtained in this way
      are similar to, but more consistent than, those obtained through measurement of
      carotid artery pressure waves by applanation tonometry. The ability to synthesise
      the ascending aortic waveform enables one to measure augmentation of late
      systolic pressure caused by arterial stiffening as well as the effects of
      antihypertensive drug therapies on systolic pressure augmentation. Results have
      shown that drugs which dilate small peripheral arteries and thereby reduce wave
      reflection (nitrates, ACE inhibitors, calcium antagonists) reduce ascending
      aortic pressure augmentation during systole, often without corresponding
      reduction in brachial or radial artery systolic pressure. These agents are more
      appropriate therapy for isolated systolic hypertension than beta-blockers and
      diuretics.

PMID- 7807514
TI  - Patch clamp analysis of the dominant plasma membrane K+ channel in root cell
      protoplasts of Plantago media L. Its significance for the P and K state.
AB  - Ion channels in the plasma membrane of root cell protoplasts of Plantago media L.
      were studied with the patch clamp technique in the cell-attached patch and
      outside-out patch configuration. An outward rectifying potassium channel was
      dominantly present in the plasma membrane. It appears responsible for the
      diffusional part, dominated by the K+ diffusion potential, of the cell membrane
      potential, in vivo. This channel is activated at potentials near to and more
      positive than the K+ diffusion potential. The dependence of this ion channel on
      K+ activity and voltage has been characterized. The current-voltage relationships
      of the open channel at various K+ concentrations are described by a four-state
      model. The membrane potential of intact protoplasts appears either dominated by
      the K+ diffusion potential, the protoplast is then said to be in the K state, or
      by the pump potential generated by the plasma membrane-bound proton pump/H+
      ATPase, the P state. An experimental procedure is described to determine in cell
      attached patch mode the state of the protoplast, either K or P state.

PMID- 7807515
TI  - Potassium currents in cultured rabbit retinal pigment epithelial cells.
AB  - Membrane potential and ionic currents were studied in cultured rabbit retinal
      pigment epithelial (RPE) cells using whole-cell patch clamp and perforated-patch
      recording techniques. RPE cells exhibited both outward and inward voltage
      dependent currents and had a mean membrane capacitance of 26 +/- 12 pF (SD, n =
      92). The resting membrane potential averaged -31 +/- 15 mV (n = 37), but it was
      as high as -60 mV in some cells. When K+ was the principal cation in the
      recording electrode, depolarization-activated outward currents were apparent in
      91% of cells studied. Tail current analysis revealed that the outward currents
      were primarily K+ selective. The most frequently observed outward K+ current was
      a voltage- and time-dependent outward current (IK) which resembled the delayed
      rectifier K+ current described in other cells. IK was blocked by
      tetraethylammonium ions (TEA) and barium (Ba2+) and reduced by 4-aminopyridine (4
      AP). In a few cells (3-4%), depolarization to -50 mV or more negative potentials
      evoked an outwardly rectifying K+ current (IKt) which showed more rapid
      inactivation at depolarized potentials. Inwardly rectifying K+ current (IKI) was
      also present in 41% of cells. IKI was blocked by extracellular Ba2+ or Cs+ and
      exhibited time-dependent decay, due to Na+ blockade, at negative potentials. We
      conclude that cultured rabbit RPE cells exhibit at least three voltage-dependent
      K+ currents. The K+ conductances reported here may provide conductive pathways
      important in maintaining ion and fluid homeostasis in the subretinal space.

PMID- 7807517
TI  - Ion transport across the early chick embryo: I. Electrical measurements, ionic
      fluxes and regional heterogeneity.
AB  - The chick blastoderm at the stage of late gastrula is a flat disc formed by three
      cell layers and exhibiting epithelial properties. Blastoderms were cultured in
      miniature chambers and their electrophysiological characteristics were determined
      under Ussing conditions. Under open-circuit condition and identical physiological
      solutions on both sides, spontaneous transblastodermal potential difference (Voc)
      of -7.5 +/- 3.3 mV (ventral side positive) was measured. Under short-circuit
      condition (transblastodermal delta V = 0 mV), the blastoderm generated short
      circuit current (Isc) of 21 +/- 8 microA/cm2, which was entirely dependent on
      extracellular sodium, sensitive to ouabain applied ventrally and independent of
      extracellular chloride. The net transblastodermal Na+ flux fully accounted for
      the measured Isc, both under control conditions and with ouabain. The total
      transblastodermal resistance (Rtot) was 390 +/- 125 omega cm2. Frequently, the
      Voc, Isc and Rtot showed spontaneous oscillations with a period of 4-5 min.
      Removal of endoderm and mesoderm did not significantly affect the electrical
      properties, indicating that the electrogenic sodium transport is generated by the
      ectoderm. The Voc and Isc measured in the area pellucida (-1.3 +/- 0.8 mV, 9.3 +/
      4.4 microA/cm2) and extraembryonic area opaca (-7.8 +/- 1.1 mV, 31.2 +/- 12.7
      microA/cm2) were significantly different. Such a heterogeneous distribution of
      electrical properties can explain the presence in the blastoderm of extracellular
      electrical currents found by using a vibrating probe.

PMID- 7807516
TI  - Modeling degranulation with liposomes: effect of lipid composition on membrane
      fusion.
AB  - Degranulation involves the regulated fusion of granule membrane with plasma
      membrane. To study the role of lipid composition in degranulation, large
      unilamellar vesicles (LUVs) of increasing complexity in lipid compositions were
      constructed and tested for Ca(2+)-mediated lipid and contents mixing. Lipid
      mixing rates of LUVs composed of phosphatidylethanolamine (PE) and
      phosphatidylserine (PS) were strongly decreased by the addition of either
      phosphatidylcholine (PC) or sphingomyelin (SM), while phosphatidylinositol (PI)
      had little effect. "Complex" LUVs of PC:PE:SM:PI:PS (24:27:20:16:13, designed to
      emulate neutrophil plasma membranes) also showed very low rates of both lipid
      mixing and contents mixing. The addition of cholesterol significantly lowered the
      Ca2+ threshold for contents mixing and increased the maximum rates of both lipid
      and contents mixing in a dose-dependent manner. Membrane remodeling, which occurs
      in neutrophil plasma membranes upon stimulation, was simulated by incorporating
      low levels of phosphatidic acid (PA) or a diacylglycerol (DAG) into complex LUVs
      containing 50% cholesterol. The addition of PA both lowered the Ca2+ threshold
      and increased the rate of contents mixing in a dose-dependent manner, while the
      DAG had no significant effect. The interaction of dissimilar LUVs was also
      examined. Contents-mixing rates of LUVs of two different cholesterol contents
      were intermediate between the rates observed for the LUVs of identical
      composition. Thus, cholesterol needed to be present in only one fusing partner to
      enhance fusion. However, for PA to stimulate fusion, it had to be present in both
      sets of LUVs. These results suggest that the rate of degranulation may be
      increased by a rise in the cholesterol level of either the inner face of the
      plasma membrane or the outer face of the granule membrane. Further, the
      production of PA can promote fusion, and hence degranulation, whereas the
      subsequent conversion of PA to DAG may reverse this promotional effect.

PMID- 7807518
TI  - Ion transport across the early chick embryo: II. Characterization and pH
      sensitivity of the transembryonic short-circuit current.
AB  - The ectoderm of the one-day chick embryo generates dorsoventrally oriented short
      circuit current (Isc) entirely dependent on extracellular sodium. At the dorsal
      cell membrane, the Isc was modified reversibly and in a concentration-dependent
      manner by: amiloride (60% decrease at 1 mM, with 2 apparent IC50S: 0.13 and 48
      microM), phlorizin (0.1 mM) or removal of glucose (30% decrease, additive to that
      of amiloride), SITS (1 mM, 13% decrease). Acidification of alkalinization of the
      dorsal (but not ventral) superfusate produced, respectively, decrease or increase
      of Isc with a pH50 of 7.64. Ba2+ (0.1-1 mM) from either side of the ectoderm
      decreased the Isc by 30%. Anthracene-9-carboxylic acid, furosemide and inducers
      of cAMP had no effect on electrophysiological properties of the blastoderm. The
      chick ectoderm is therefore a highly polarized epithelium containing, at the
      dorsal membrane, the high and low affinity amiloride-sensitive Na+ channels,
      Na(+)-glucose cotransporter, K+ channels and pH sensitivity, and, at the ventral
      membrane, the Na+, K(+)-ATPase and K+ channels. The Na+ transport reacts to pH,
      but lacks the cAMP regulatory system, well known in many epithelia. The active
      Na+ transport drives glucose and fluid into the intraembryonic space, across and
      around the blastoderm which, in the absence of blood circulation, could secure
      renewal of extracellular fluid and disposal of wastes and thus maintain the cell
      homeostasis.

PMID- 7807519
TI  - Amino acid transport system y+L of human erythrocytes: specificity and cation
      dependence of the translocation step.
AB  - The transport specificity of system y+L of human erythrocytes was investigated
      and the carrier was found to accept a wide range of amino acids as substrates.
      Relative rates of entry for various amino acids were estimated from their trans
      effects on the unidirectional efflux of L-[14C]-lysine. Some neutral amino acids,
      L-lysine and L-glutamic acid induced marked trans-acceleration of labeled lysine
      efflux; saturating concentrations of external L-leucine and L-lysine increased
      the rate by 5.3 +/- 0.63 and 6.2 +/- 0.54, respectively. The rate of
      translocation of the carrier-substrate complex is less dependent on the structure
      of the amino acid than binding. Translocation is slower for the bulkier analogues
      (L-tryptophan, L-phenylalanine); smaller amino acids, although weakly bound, are
      rapidly transported (L-alanine, L-serine). Half-saturation constants (+/- SEM)
      calculated from this effect (L-lysine, 10.32 +/- 0.49 microM and L-leucine, 11.50
      +/- 0.50 microM) agreed with those previously measured in cis-inhibition
      experiments. The degree of trans-acceleration caused by neutral amino acids did
      not differ significantly in Na+, Li+ or K+ medium, whereas the affinity for
      neutral amino acids was dramatically decreased if Na+ or Li+ were replaced by K+.
      The observation that specificity is principally expressed in substrate binding
      indicates that the carrier reorientation step is largely independent of the
      forces of interaction between the carrier and the transport site.

PMID- 7807520
TI  - Ca(2+)-activated K+ channels are involved in regulatory volume decrease in acinar
      cells isolated from the rat lacrimal gland.
AB  - The volumes of acinar cells isolated from rat lacrimal gland were measured on
      computer by video-imaging. Cells were found to swell on exposure to hypotonic
      solutions; they subsequently exhibited a regulatory volume decrease (RVD). RVD
      was inhibited in the absence of extracellular Ca2+, and by the K+ channel blocker
      tetraethylammonium chloride (2 mM TEA+). The possible involvement of K+ channels
      in RVD was further investigated in cell-attached patches. Exposing the cells to a
      hypotonic solution activated channels with a conductance of 141 +/- 6 pS (n =
      11). These channels were partially blocked by 0.5 mM TEA+, and channel activation
      was not observed in the absence of extracellular Ca2+. Experiments in the inside
      out patch configuration demonstrated that the channels activated by hypotonic
      stress were "maxi" Ca(2+)-activated K+ channels. It is concluded that the opening
      of these channels plays an important role in RVD, by facilitating K+ loss from
      the cell.

PMID- 7807522
TI  - Monovalent amidiniums block calcium channels in chick sensory neurons.
AB  - The effect of amidiniums on high-threshold Ca2+ channel currents (ICa) was
      studied in chick dorsal root ganglion neurons. Guanidinium reduced ICa in a dose
      dependent fashion. The block was relieved by increasing the concentration of the
      permeant ions, Ba2+ or Ca2+, suggesting a competition for a common binding site
      within the channel. Formamidinium and methyl-guanidinium suppressed ICa with
      similar potencies, whereas L-arginine had no effect. A neutral amidine, urea,
      increased ICa. In Ca(2+)-free solutions guanidinium and Na+ permeated through the
      Ca2+ channel equally well. Structure-activity relationship obtained for blocking
      efficacies of different amidiniums are used to discuss possible configurations of
      the selectivity filter in the Ca2+ channel.

PMID- 7807521
TI  - Arginyl residues are involved in the transport of Fe2+ through the plasma
      membrane of the mammalian reticulocyte.
AB  - Sealed reticulocyte ghosts were treated with reagents that modify a variety of
      amino acid residues. Only ninhydrin and phenylglyoxal, both modifiers of arginyl
      residues, produced inhibition of the initial rate of 59Fe2+ uptake. The
      inhibition (i) was dependent on the concentration of ninhydrin or phenylglyoxal,
      (ii) increased from pH 7 to 9, a feature of the modification of arginine by
      ninhydrin or phenylglyoxal, and (iii) was blocked when Fe2+ was present during
      the modification step. A23187, an effective membrane Fe2+ transporter, diminished
      the inhibitory effect of ninhydrin and phenylglyoxal, indicative that the
      transport of iron through the membrane, and not a secondary process, was
      selectively inhibited. We conclude that the iron transporter from the plasma
      membrane of erythroid cells has one or more arginyl residues in a segment
      accessible to ninhydrin or phenylglyoxal, and that this residue is involved in
      the transmembrane transport of iron.

PMID- 7807523
TI  - A tetraethylammonium-insensitive inward rectifier K+ channel in Muller cells of
      the turtle (Pseudemys scripta elegans) retina.
AB  - Ion channels present in isolated glial (Muller) cells from the retina of the
      turtle (Pseudemys scripta elegans) were studied with the patch clamp technique.
      The predominant conductance in these cells was due to an inward rectifying
      potassium current. The whole-cell conductance of the inward rectifier was 20.2 +/
      1.9 nS (n = 7 cells) in a standard extracellular saline solution (3 mM
      extracellular potassium). This conductance was dependent on the extracellular
      potassium concentration, with a 2.88-fold change in conductance per tenfold shift
      in concentration. The relative permeability sequence to potassium of the inward
      rectifier was found to be: potassium (1.0) > rubidium (0.7) > ammonium (0.2) >
      lithium (0.1) = sodium (0.1), which corresponded to the Eisenman sequence IV or V
      for a strong-field-strength potassium binding site on the channel. The single
      channel conductance measured in cell-attached patches with potassium chloride
      (150 mM) in the pipette was 68.5 +/- 6.0 pS (n = 3 patches). The inward rectifier
      current was not blocked by extracellular tetraethylammonium (TEA+, 20 mM), but
      was blocked by extracellular barium (5 mM) or cesium (5 mM). The TEA+
      insensitivity of the inward rectifier potassium channel in Muller cells is
      unusual, given that this type of channel in most excitable cells is sensitive to
      micromolar concentrations of this compound, and may be a characteristic of inward
      rectifier potassium channels that are primarily involved with extracellular
      potassium regulation.

PMID- 7807524
TI  - Immunochemical characterization of the gap junction protein connexin45 in mouse
      kidney and transfected human HeLa cells.
AB  - Antibodies to the gap junction protein connexin45 (Cx45) were obtained by
      immunizing rabbits with fusion protein consisting of glutathione S-transferase
      and 138 carboxy-terminal amino acids of mouse Cx45. As shown by immunoblotting
      and immunofluorescence, the affinity-purified antibodies recognized Cx45 protein
      in transfected human HeLa cells as well as in the kidney-derived human and
      hamster cell lines 293 and BHK21, respectively. In Cx45-transfected HeLa cells,
      this protein is phosphorylated as demonstrated by immunoprecipitation after
      metabolic labeling. The phosphate label could be removed by treatment with
      alkaline phosphatase. A weak phosphorylation of Cx45 protein was also detected in
      the cell lines 293 and BHK21. Treatment with dibutyryl cyclic adenosine- or
      guanosine monophosphate (cAMP, cGMP) did not alter the level of Cx45
      phosphorylation, in either Cx45 transfectants or in 293 or BHK21 cells. The
      addition of the tumor-promoting agent phorbol 12-myristate 13-acetate (TPA) led
      to an increased 32P phosphate incorporation into the Cx45 protein in transfected
      cells. The Cx45 protein was found in homogenates of embryonic brain, kidney, and
      skin, as well as of adult lung. In kidney of four-day-old mice, Cx45 was detected
      in glomeruli and distal tubules, whereas connexin32 and -26 were coexpressed in
      proximal tubules. No connexin43 protein was detected in proximal tubules. No
      connexin43 protein was detected in renal tubules and glomeruli at this stage of
      development. Our results suggest that cells in proximal and distal tubules are
      interconnected by gap junction channels made of different connexin proteins. The
      Cx45 antibodies characterized in this paper should be useful for investigations
      of Cx45 in renal gap junctional communication.

PMID- 7807525
TI  - Rundown and reactivation of ATP-sensitive potassium channels (KATP) in mouse
      skeletal muscle.
AB  - Dissociated single fibers from the mouse flexor digitorum brevis (FDB) muscle
      were used in patch clamp experiments to investigate the mechanisms of activation
      and inactivation of KATP in mammalian skeletal muscle. Spontaneous rundown of
      channel activity, in many excised patches, occurred gradually over a period of 10
      20 min. Application of 1.0 mM free-Ca2+ to the cytoplasmic side of the patch
      caused irreversible inactivation of KATP within 15 sec. Ca(2+)-induced rundown
      was not prevented by the presence of 1.0 microM okadaic acid or 2.0 mg ml-1 of an
      inhibitor of calcium-activated neutral proteases, a result consistent with the
      conclusion that phosphatases or calcium-activated neutral proteases were not
      involved in the rundown process. Application of 1.0 mM Mg.ATP to Ca(2+)
      inactivated KATP caused inhibition of residual activity but little or no
      reactivation of the channels upon washout of ATP, even in the presence of the
      catalytic subunit of cyclic AMP-dependent protein kinase (10 U ml-1). Mg.ATP also
      failed to reactivate KATP, even after only partial spontaneous rundown, despite
      the presence of channels that could be activated by the potassium channel opener
      BRL 38227. Nucleotide diphosphates (500 microM; CDP, UDP, GDP and IDP) caused
      immediate and reversible opening of Ca(2+)-inactivated KATP. Reactivation of KATP
      by ADP (100 microM) increased further upon removal of the nucleotide. In contrast
      to KATP from cardiac and pancreatic cells, there was no evidence for
      phosphorylation of KATP from the surface sarcolemma of dissociated single fibers
      from mouse skeletal muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7807526
TI  - Sodium transport through the amiloride-sensitive Na-Mg pathway of hamster red
      cells.
AB  - Previous work showed that in hamster red cells the amiloride-sensitive (AS) Na+
      influx of 0.8 mmol/liter cells/hr is not mediated by Na-H exchange as in other
      red cells, but depends upon intracellular Mg2+ and can be increased by 40-fold by
      loading cells with Mg2+ to 10 mM. The purpose of this study was to verify the
      connection of AS Na+ influx with Na-dependent, amiloride-sensitive Mg2+ efflux
      and to utilize AS Na+ influx to explore that pathway. Determination of
      unidirectional influx of Na+ and net loss of Mg2+ in parallel sets of cells
      showed that activation by extracellular [Na+] follows a simple Michaelis-Menten
      relationship for both processes with a Km of 105-107 mM and that activation of
      both processes is sigmoidally dependent upon cytoplasmic [Mg2+] with a [Mg2+]0.5
      of 2.1-2.3 mM and a Hill coefficient of 1.8. Comparison of Vmax for both sets of
      experiments indicated a stoichiometry of 2 Na:1 Mg. Amiloride inhibits Na+ influx
      and Mg2+ extrusion in parallel (Ki = 0.3 mM). Like Mg2+ extrusion, amiloride
      sensitive Na+ influx shows an absolute requirement for cytoplasmic ATP and is
      increased by cell swelling. Hence, amiloride-sensitive Na+ influx in hamster red
      cells appears to be through the Na-Mg exchange pathway. There was no amiloride
      sensitive Na+ efflux in hamster red cells loaded with Na+ and incubated with high
      [Mg2+] in the medium with or without external Na+, nor with ATP depletion. Hence,
      this is not a simple Na-Mg exchange carrier.

PMID- 7807527
TI  - Temperature-dependent modification of divalent cation flux in the rat parotid
      gland basolateral membrane.
AB  - Divalent cation (Mn2+, Ca2+) entry into rat parotid acinar cells is stimulated by
      the release of Ca2+ from the internal agonist-sensitive Ca2+ pool via a mechanism
      which is not yet defined. This study examines the effect of temperature on Mn2+
      influx into internal Ca2+ pool-depleted acini (depl-acini, as a result of
      carbachol stimulation of acini in a Ca(2+)-free medium for 10 min) and passive
      45Ca2+ influx in basolateral membrane vesicles (BLMV). Mn2+ entry into depl-acini
      was decreased when the incubation temperature was lowered from 37 to 4 degrees C.
      At 4 degrees C, Mn2+ entry appeared to be inactivated since it was not increased
      by raising extracellular [Mn2+] from 50 microM up to 1 mM. The Arrhenius plot of
      depletion-activated Mn2+ entry between 37 and 8 degrees C was nonlinear, with a
      change in the slope at about 21 degrees C. The activation energy (Ea) increased
      from 10 kcal/mol (Q10 = 1.7) at 21-37 degrees C to 25 kcal/mol (Q10 = 3.0) at 21
      8 degrees C. Under the same conditions, Mn2+ entry into basal (unstimulated)
      cells and ionomycin (5 microM) permeabilized depl-acini exhibit a linear
      decrease, with Ea of 7.8 kcal/mol (Q10 = 1.5) and 6.2 kcal/mol (Q10 < 1.5),
      respectively. These data suggest that depletion-activated Mn2+ entry into parotid
      acini is regulated by a mechanism which is strongly temperature dependent and
      distinct from Mn2+ entry into unstimulated acini.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7807528
TI  - Cl- and K+ channel currents during the action potential in Chara. Simultaneous
      recording of membrane voltage and patch currents.
AB  - Patch currents in the cell attached-mode and action potentials (AP) have been
      recorded simultaneously in internodal cells of Chara corallina. The action
      potentials are closely correlated with transient patch currents. With pipettes
      containing either 50 mM CaCl2 or 100 mM KCl plus 1 or 5 mM CaCl2, these
      transients measured up to 100 to 200 pA per patch at zero mV. Transients had a
      mean duration (time during which the current was > or = half maximum peak
      amplitude) of about 1 sec, a maximum slope for current rising of about 400 pA sec
      1 and a maximum rate of about 100 pA sec-1 for current decay, with no obvious
      effect of external Ca2+ on either of these parameters. In well-resolved
      recordings of current transients triggered by an action potential (AP),
      activities of two types of Cl--conducting channels (15 and 38 pS) have been
      identified. Since activity of these channels was only observed during action
      potentials but not upon positive voltage steps, these channels are not directly
      voltage gated but point to a cytoplasmic gating factor which accumulates during
      excitation and propagates from excited areas to the patch. A K(+)-conducting
      channel (40 pS) could be identified as well during an AP, when 100 mM KCl was in
      the pipette solution. The activity of this channel relaxed at the end of the APs
      with a time constant of about 3 sec. Stimulated activity of this channel is
      understood to cause the repolarization overshoot during the final phase of the
      action potential, whereas the transient activation of the Cl- channels determines
      the fast voltage changes of the action potential.

PMID- 7807529
TI  - Laser treatment for snoring.
AB  - CO2 Laser Assisted Uvulopalatoplasty (LAUP) is a safe and effective, ambulatory
      treatment for snoring, performed under local anesthesia. By means of multiple
      sessions, the LAUP progressively enlarges the airspace of the oropharynx,
      reducing the bulk of the vibrating soft palate and wide posterior tonsil pillars.
      Advantages are that it is simple, reliable, painless, bloodless and outpatient.
      Disadvantages are the multiple sessions, the high technical effort, and Laser
      costs.

PMID- 7807530
TI  - Are you sorry you went to medical school?

PMID- 7807531
TI  - The iron gate.

PMID- 7807532
TI  - Fine needle aspiration of parotid masses.

PMID- 7807533
TI  - Chromatin self-organization by mutation bias.
AB  - Proteins, on binding to a DNA sequence, alter the frequency and quality of
      mutations that occur in the sequence. This represents a reverse flow of
      information from proteins to DNA. Nucleosome binding causes patterns of UV
      induced damage which, when converted to mutations by replication, will phase
      nucleosomes. We propose that DNA binding proteins create their own high- or low
      affinity binding sites along DNA sequences by biased mutational pressure.

PMID- 7807534
TI  - Synonymous substitutions are clustered in enterobacterial genes.
AB  - The spatial distribution of synonymous substitutions in enterobacterial genes is
      investigated. It is shown that synonymous substitutions are significantly
      clustered in such a way that a synonymous substitution in one codon elevates the
      rate of synonymous substitution in an adjacent codon by about 10%. The level of
      clustering does not appear to be related to the level of gene expression, and it
      is restricted to a range of two or three codons. There are at least three
      possible explanations: (1) sequence-directed mutagenesis, (2) recombination, and
      (3) selection.

PMID- 7807535
TI  - Degenerating gypsy retrotransposons in a male fertility gene on the Y chromosome
      of Drosophila hydei.
AB  - During the evolution of the Y chromosome of Drosophila hydei, retrotransposons
      became incorporated into the lampbrush loop pairs formed by several of the male
      fertility genes on this chromosome. Although insertions of retrotransposons are
      involved in many spontaneous mutations, they do not affect the functions of these
      genes. We have sequenced gypsy elements that are expressed as constituents of
      male fertility gene Q in the lampbrush loop pair Nooses. We find that these gypsy
      elements are all truncated and specifically lost those sequences that may
      interfere with the continuity of lampbrush loop transcription. Only defective
      coding regions are found within the loop. Gypsy is not transcribed in loops of
      many other Drosophila species harboring the family. These results suggest that
      any contribution of gypsy to the function of male fertility gene Q does not
      depend on a conserved DNA sequence.

PMID- 7807536
TI  - Dynamic equilibrium between insertion and excision of P elements in highly inbred
      lines from an M' strain of Drosophila melanogaster.
AB  - Six highly inbred lines of Drosophila melanogaster extracted from an M' strain
      (in the P/M system of hybrid dysgenesis) were studied for the evolution of the
      number and chromosomal location of complete and defective P elements through
      generations 52-200. These lines possessed full-sized P elements but differed in
      their cytotype (M or P). Three lines with P cytotype and full-sized P elements at
      site 1A had a constant P copy number over generations with low rates of insertion
      and excision. Three lines with M cytotype and at least one full-sized P element
      accumulated P copies over the generations and reached a plateau near generation
      196, at which rates of transposition and excision were equal to 1.2 x 10(-3) to 3
      x 10(-3) events per element per generation. At that time these three lines still
      presented an M cytotype, produced transposase, and were able to regulate P copy
      number. The similarity at equilibrium between insertion and excision rates was
      exactly what was expected from theoretical models for a self-regulated element.
      The large number of generations necessary to attain the equilibrium in copy
      number indicates, however, that caution may be de rigueur when testing
      theoretical models of copy-number containment based on transposition and excision
      rate comparison.

PMID- 7807537
TI  - A repetitive DNA family, conserved throughout the evolution of free-living
      nematodes.
AB  - This paper concerns the molecular evolution of a tandemly repeated DNA family,
      RcC9, originally identified in Caenorhabditis elegans. The minimum unit of
      periodicity of this family is the pentanucleotide [nGAAn] and its complement
      [nTTCn] recurring several times in alternating tandem arrays. This consensus
      sequence is identical to that of the heat-shock element (HSE). Multiple HSEs are
      present in the regulatory regions of heat-inducible genes in a wide range of
      eukaryotic species; HSEs mediate transcriptional activation through the binding
      of the heat-shock factor (HSF). I describe some repeated DNA families sharing
      this same consensus and found in nematode species other than C. elegans. Although
      the consensus is conserved, the repeated sequence diverged between species to the
      point that cross-hybridization is abolished. Evolutionary implications will be
      discussed.

PMID- 7807538
TI  - Characterization of two abundant satellite DNAs from the mealworm Tenebrio
      obscurus.
AB  - Two highly abundant satellite DNAs comprise 36% of the Tenebrio obscurus
      (Tenebrionidae, Coleoptera) genome. They are designated as satellite I and
      satellite II with the monomer length of 344 and 142 base pairs (bp),
      respectively. Both satellites differ in their nucleotide (nt) sequences, but the
      frequency of point mutations, well-conserved length of monomer variants,
      stretches of shared mutations characteristic for the process of gene conversion,
      and distribution of both satellites in regions of centromeric heterochromatin of
      all chromosomes indicate that the same evolutionary processes act on both of them
      with the same, or similar, rate. While satellite I shares no sequence similarity
      with any other known nt sequence, satellite II is 79.7% homologous with the
      highly abundant satellite from closely related Tenebrio molitor. Difference in
      the frequency of point mutations and absence of shared mutations indicating gene
      conversion strongly suggest that in these two closely related species mutational
      processes affecting satellite DNAs seem to be changed. Retarded electrophoretic
      mobility, due to sequence-induced curvature of DNA helix axis, was observed for
      T. obscurus satellite II, but not for satellite I. Although evolutionary
      processes act with different rates in T. obscurus and T. molitor satellites the
      monomer length and sequence-induced curvature are well preserved in both 142-bp
      satellites, as well as in, at the nt sequence level completely divergent, Palorus
      ratzeburgii (Tenebrionidae) satellite, indicating potential importance of these
      parameters in their evolution.

PMID- 7807539
TI  - Phylogenetic relationships reveal recombination among isolates of cauliflower
      mosaic virus.
AB  - Isolates of cauliflower mosaic virus (CaMV) differ in host range and
      symptomatology. Knowledge of their sequence relationships should assist in
      identifying nucleotide sequences responsible for isolate-specific characters.
      Complete nucleotide sequences of the DNAs of eight isolates of CaMV were aligned
      and the aligned sequences were used to analyze phylogenetic relationships by
      maximum likelihood, bootstrapped parsimony, and distance methods. Isolates found
      in North America clustered separately from those isolated from other parts of the
      world. Additional isolates, for which partial sequences were available, were
      incorporated into phylogenetic analysis of the sequences of genome segments
      corresponding to individual protein coding regions or the large intergenic region
      of CaMV DNA. The analysis revealed several instances where the position of an
      isolate on a tree for one coding region did not agree with the position of the
      isolate on the tree for the complete genome or with its position on trees for
      other coding regions. Examination of the distribution of shared residue types of
      phylogenetically informative positions in anomalous regions suggested that most
      of the anomalies were due to recombination events during the evolution of the
      isolates. Application of an algorithm that searches for segments of significant
      length that are identical between pairs of isolates or contain a significantly
      high concentration of polymorphisms suggested two additional recombination events
      between progenitors of the isolates studied and an event between the XinJing
      isolate and a CaMV not represented in the data set. An earlier phylogenetic
      origin for CaMV than for carnation etched ring virus, the caulimovirus used as
      outgroup in these analyses, was deduced from the position of the outgroup with
      North American isolates in some trees, but with non-North American isolates in
      other trees.

PMID- 7807540
TI  - Phylogenetic relationships among eutherian orders estimated from inferred
      sequences of mitochondrial proteins: instability of a tree based on a single
      gene.
AB  - The phylogenetic relationships among Primates (human), Artiodactyla (cow),
      Cetacea (whale), Carnivora (seal), and Rodentia (mouse and rat) were estimated
      from the inferred amino acid sequences of the mitochondrial genomes using
      Marsupialia (opossum), Aves (chicken), and Amphibia (Xenopus) as an outgroup. The
      overall evidence of the maximum likelihood analysis suggests that Rodentia is an
      outgroup to the other four eutherian orders and that Cetacea and Artiodactyla
      form a clade with Carnivora as a sister taxon irrespective of the assumed model
      for amino acid substitutions. Although there remains an uncertainty concerning
      the relation among Artiodactyla, Cetacea, and Carnivora, the existence of a clade
      formed by these three orders and the outgroup status of Rodentia to the other
      eutherian orders seems to be firmly established. However, analyses of individual
      genes do not necessarily conform to this conclusion, and some of the genes reject
      the putatively correct tree with nearly 5% significance. Although this
      discrepancy can be due to convergent or parallel evolution in the specific genes,
      it was pointed out that, even without a particular reason, such a discrepancy can
      occur in 5% of the cases if the branching among the orders in question occurred
      within a short period. Due to uncertainty about the assumed model underlying the
      phylogenetic inference, this can occur even more frequently. This demonstrates
      the importance of analyzing enough sequences to avoid the danger of concluding an
      erroneous tree.

PMID- 7807541
TI  - Using protein synthesis inhibitors to establish the phylogenetic relationships of
      the Sulfolobales order.
AB  - The sensitivity of the cell-free protein synthesis systems from Acidanus
      brierleyi, Acidianus infernus, and Metallosphaera sedula, members of the archaeal
      order Sulfolobales, to 40 antibiotics with different specificities has been
      studied. The sensitivity patterns were compared to those of Sulfolobus
      solfataricus and other archaeal, bacterial, and eukaryotic systems. The
      comparative analysis shows that ribosomes from the sulfolobales are the most
      refractory to inhibitors of protein synthesis described so far. The sensitivity
      results have been used to ascertain in phylogenetic relationships among the
      members of the order Sulfolobales. The evolutionary significance of these results
      are analyzed in the context of the phylogenetic position of this group of extreme
      thermophilic microorganisms.

PMID- 7807542
TI  - An empirical comparison of distance matrix techniques for estimating codon usage
      divergence.
AB  - The quantitative description of codon usage divergence among taxa is a two-step
      process involving first the calculation of a standardized measure of intertaxon
      divergence for each possible pair of taxa followed by a summary and visual
      display of the patterns among the taxa inherent in these measures. Three
      different measures have been proposed in the literature, and three different
      summaries have been used. These different techniques are empirically compared
      using a data set consisting of gene sequences from seven species of Apicomplexa.
      The results suggest that the manhattan distance measure may be preferable to the
      use of the chi-square measure, although the separation of amino acid usage and
      codon usage by the genetic distance produces theoretical advantages. The
      multidimensional scaling ordination and unweighted pair-group clustering are both
      successful in displaying the patterns, while the eigenanalysis ordination is not.

PMID- 7807543
TI  - HSP70 phylogeny and the relationship between archaebacteria, eubacteria, and
      eukaryotes.

PMID- 7807544
TI  - Which is the most conserved group of proteins? Homology-orthology, paralogy,
      xenology, and the fusion of independent lineages.

PMID- 7807545
TI  - Transbilayer diffusion of divalent cations into liposomes mediated by lipidic
      particles of phosphatidate.
AB  - Liposomes formed from egg-yolk phosphatidylcholine:egg-yolk phosphatidate (molar
      ratio 2:1) containing pBR322 DNA and DNase I were induced to form, with divalent
      cations, bilayer/nonbilayer phase transitions of phosphatidate which allowed
      cation diffusion into liposomes; then cation diffusion was measured by the
      activation of the hydrolysis of DNase I on DNA. The formation of phosphatidate
      transitions on liposomes was demonstrated by freeze-fracture and 31P NMR, and a
      direct correlation between the formation of phosphatidate transitions and the
      transbilayer diffusion of cations was found: only Ca2+ and Mn2+, which induce
      phase transitions, were able to penetrate liposomes and triggered the DNase I
      activity; in addition, Ca2+ at higher concentrations (10 mM) caused fusion of
      liposomes, whereas Mn2+ did not, suggesting that transitions induced by Mn2+
      participated only in the diffusion of this ion; furthermore, Mg2+ neither formed
      phase transitions nor triggered the enzymatic activity. The liposomes studied
      represent more dynamic structures that can form phosphatidate structures involved
      in both (1) the interchange of divalent cations with the surroundings, thereby
      modulating encapsulated enzymes, and (2) the fusion of lipid vesicles probably
      implicated in the enrichment of liposomal content in the early Precambian Earth.

PMID- 7807546
TI  - Contrasting rates of nucleotide substitution in the X-linked and Y-linked zinc
      finger genes.
AB  - We have sequenced the entire exon (approximately 1.180 bp) encoding the zinc
      finger domain of the X-linked and Y-linked zinc finger genes (ZFX and ZFY,
      respectively) in the orangutan, the baboon, the squirrel monkey, and the rat; a
      total of 9,442 bp were sequenced. The ratio of the rates of synonymous
      substitution in the ZFY and ZFX genes is estimated to be 2.1 in primates. This is
      close to the ratio of 2.3 estimated from primate ZFY and ZFX intron sequences and
      supports the view that the male-to-female ratio of mutation rate in humans in
      considerably higher than 1 but not extremely large. The ratio of synonymous
      substitution rates in ZFY and ZFX is estimated to be 1.3 in the rat lineage but
      4.2 in the mouse lineage. The former is close to the estimate (1.4) from introns.
      The much higher ratio in the mouse lineage (not statistically significant) might
      have arisen from relaxation of selective constraints. The synonymous divergence
      between mouse and rat ZFX is considerably lower than that between mouse and rat
      autosomal genes, agreeing with previous observations and providing some evidence
      for stronger selective constraints on synonymous changes in X-linked genes than
      in autosomal genes. At the protein level ZFX has been highly conserved in all
      placental mammals studied while ZFY has been well conserved in primates and foxes
      but has evolved rapidly in mice and rats, possibly due to relaxation of
      functional constraints as a result of the development of X-inactivation of ZFX in
      rodents. The long persistence of the ZFY-ZFX gene pair in mammals provides some
      insight into the process of degeneration of Y-linked genes.

PMID- 7807547
TI  - The Dictyostelium discoideum mitochondrial genome: a primordial system using the
      universal code and encoding hydrophilic proteins atypical of metazoan
      mitochondrial DNA.
AB  - A 3,345-bp fragment of Dictyostelium discoideum mitochondrial DNA (mtDNA) has
      been sequenced. This fragment contained the 80-kDa subunit of complex I
      (NADH:ubiquinone oxidoreductase), encoding a predicted amino acid sequence of 688
      residues and a molecular mass of 79,805 daltons which is nuclear encoded in other
      metazoa. The C-terminus of the D. discoideum complex I gene shared a 10-bp
      overlap with NADH:ubiquinone oxidoreductase chain 5 (ND5), while 21 bp 5' were
      three tRNA genes (two isoleucine and a histidine) and a further 25 bp 5' of these
      genes is the partial sequence (104 residues) of an unidentified open reading
      frame (ORF104). Both the 80-kDa subunit and the ORF104 were hydrophilic and
      highly charged, suggesting they are not membrane associated, unlike most
      mitochondrially encoded proteins in the metazoa. Sequence analysis of the 80-kDa
      subunit, its adjacent ND5 gene, and ORF104 indicates the universal stop codon
      TGA, which codes for tryptophan in nearly all nonplant mtDNA, is either
      unassigned or coding for a stop codon in D. discoideum. The large size of the
      mitochondrial genome (54 kb), the lack of intergenic sequence, and the apparent
      use of the universal code suggest D. discoideum mtDNA may encode many primitive
      genes that are nuclear encoded in higher organisms.

PMID- 7807548
TI  - Evolutionary analysis of cytochrome b sequences in some Perciformes: evidence for
      a slower rate of evolution than in mammals.
AB  - To obtain information relative to the phylogenesis and microevolutionary rate of
      fish mitochondrial DNA, the nucleotide sequence of cytochrome b gene in seven
      fish species belonging to the order of Perciformes was determined. Sequence
      analysis showed that fish mitochondrial DNA has a nucleotide compositional bias
      similar to that of sharks but lower compared to mammals and birds. Quantitative
      evolutionary analysis, carried out by using a markovian stochastic model,
      clarifies some phylogenetic relationships within the Perciformes order,
      particularly in the Scombridae family, and between Perciformes, Gadiformes,
      Cypriniformes, and Acipenseriformes. The molecular clock of mitochondrial DNA was
      calibrated with the nucleotide substitution rate of cytochrome b gene in five
      shark species having divergence times inferred from paleontological estimates.
      The results of such analysis showed that Acipenseriformes diverged from
      Perciformes by about 200 MY, that the Perciformes common ancestor dates back to
      150 MY, and that fish mitochondrial DNA has a nucleotide substitution rate three
      to five times lower than that of mammals.

PMID- 7807550
TI  - Evolutionary role of abortive transcript as a primer for DNA replication.
AB  - Abortive cycling features transcription initiation by RNA polymerase in both
      prokaryote and eukaryote. It is known that T7 RNA polymerase produces abortive
      transcripts up to eight ribonucleotides in length depending on the initial
      sequence of the DNA message. On the other hand, T7 RNA polymerase initiates DNA
      replication from the T7 primary origin by synthesizing primers. And the shortest
      primer from the phi l.lB promoter in the primary origin also seems to be eight
      ribonucleotides in length. Therefore, it is likely that the longest abortive
      transcript serves as the shortest primer for T7 DNA replication from the primary
      origin. Considering that promoters often exist in DNA replication origins for
      example, E. coli oriC and many eukaryotic origins, the early DNA replication
      system appears to have taken advantage of the abortive cycling of RNA-dependent
      RNA polymerase that already existed before the emergence of DNA world. The
      evolutionary primitive RNA polymerase could do both transcription and priming of
      DNA replication. Accordingly, abortive cycling would play an important role in
      evolution at the emergence of DNA world. The priming activity of the primitive
      RNA polymerase would be taken over by primase later, which seems to be a
      specialized RNA polymerase for abortive cycling.

PMID- 7807549
TI  - On hypervariability at the reactive center of proteolytic enzymes and their
      inhibitors.
AB  - The pattern of synonymous and nonsynonymous substitutions at the reactive center
      of proteases (kallikrein) and their inhibitors (alpha 1-antitrypsin and serpin)
      was examined. In the case of alpha 1-antitrypsin, the proportion of different
      nonsynonymous sites exceeds that of different synonymous sites at the reactive
      center for sequence pairs of recent duplication. The result indicates that the
      positive selection has operated after duplication to increase functional
      diversity. In the cases of kallikrein, serpin, and remote sequence pairs of alpha
      1-antitrypsin, the proportion of different synonymous sites at the reactive
      center exceeds that of different synonymous sites at the remaining region. The
      result indicates that gene conversion followed by natural selection is working.
      On the whole, it is concluded that hypervariability of amino acids at the
      reactive center is generated by an interaction among natural selection, random
      genetic drift, point mutation, and gene conversion. Gene duplication may provide
      potential for them to interact.

PMID- 7807551
TI  - Analysis of peptides from known proteins: clusterization in sequence space.
AB  - A combinatorial sequence space (CSS) model was introduced to represent sequences
      as a set of overlapping k-tuples of some fixed length which correspond to points
      in the CSS. The aim was to analyze clusterization of protein sequences in the CSS
      and to test various hypotheses about the possible evolutionary basis of this
      clusterization. The authors developed an easy-to-use technique which can reveal
      and analyze such a clusterization in a multidimensional CSS. Application of the
      technique led to an unexpectedly high clusterization of points in the CSS
      corresponding to k-tuples from known proteins. The clusterization could not be
      inferred from nonuniform amino acid frequencies or be explained by the influence
      of homologous data. None of the tested possible evolutionary and structural
      factors could explain the clusterization observed either. It looked as if certain
      protein sequence variations occurred and were fixed in the early course of
      evolution. Subsequent evolution (predominantly neutral) allowed only a limited
      number of changes and permitted new variants which led to preservation of certain
      k-tuples during the course of evolution. This was consistent with the theory of
      exon shuffling and protein block structure evolution. Possible applications of
      sequence space features found were also discussed.

PMID- 7807552
TI  - Evolution of the proteinase inhibitor I family and apparent lack of
      hypervariability in the proteinase contact loop.
AB  - A protein phylogenetic tree was constructed from 24 homologous proteinase
      inhibitor I sequences identified in the EMBL/Genbank and Swiss-Prot databases and
      from translated amino acid data from four constitutive cDNA clones of proteinase
      inhibitor I characterized from potato tuber mRNA. The tree suggests that
      divergence of at least four paralogous proteins with functional specialization
      occurred at different times during the evolutionary history of the proteinase
      inhibitor I family. Five distinct regions in the primary structure, earlier
      identified by structural studies, were used to analyze the inhibitor family for
      hypervariability (Creighton and Darby, Trends Biochem Sci 14:319-324, 1989).
      Mutations did not occur with higher-than-random frequency within the proteinase
      binding region. When isoinhibitor, orthologous, or paralogous data subsets were
      subsequently analyzed the same results were obtained. Comparison of the amino
      acid sequences for all the known potato proteinase isoinhibitor I proteins
      identified ten highly variable sites. These also were distributed randomly. Thus
      hypervariability, which has been observed in all other serine proteinase
      inhibitor families to date, appears to be lacking in the proteinase inhibitor I
      family.

PMID- 7807553
TI  - Amino acid sequence of the Homo sapiens brain 21-23-kDa protein (neuropolypeptide
      h3), comparison with its counterparts from Rattus norvegicus and Bos taurus
      species, and expression of its mRNA in different tissues.
AB  - The amino acid sequence of neuropolypeptide h3 from Homo sapiens brain has been
      determined. It revealed that h3 is the exact counterpart of the 21-kDa protein
      from Bos taurus brain and the 23-kDa protein from Rattus norvegicus brain: The
      three proteins belong to the same 21-23-kDa protein family. Multiple tissue
      Northern blots showed that the mRNA encoding the 21-23-kDa protein is expressed
      in different amounts according to tissues and species; it is particularly
      abundant in Rattus norvegicus testis.

PMID- 7807555
TI  - Otitis media with effusion in young children. Guideline overview. Agency for
      Health Care Policy and Research, Rockville, Maryland.

PMID- 7807556
TI  - Health-care reform: the National Medical Association's number one priority.

PMID- 7807554
TI  - Molecular pathways to parallel evolution: I. Gene nexuses and their morphological
      correlates.
AB  - Aspects of the regulatory interactions among genes are probably as old as most
      genes are themselves. Correspondingly, similar predispositions to changes in such
      interactions must have existed for long evolutionary periods. Features of the
      structure and the evolution of the system of gene regulation furnish the
      background necessary for a molecular understanding of parallel evolution.
      Patently "unrelated" organs, such as the fat body of a fly and the liver of a
      mammal, can exhibit fractional homology, a fraction expected to become subject to
      quantitation. This also seems to hold for different organs in the same organism,
      such as wings and legs of a fly. In informational macromolecules, on the other
      hand, homology is indeed all or none. In the quite different case of organs,
      analogy is expected usually to represent attenuated homology. Many instances of
      putative convergence are likely to turn out to be predominantly parallel
      evolution, presumably including the case of the vertebrate and cephalopod eyes.
      Homology in morphological features reflects a similarity in networks of active
      genes. Similar nexuses of active genes can be established in cells of different
      embryological origins. Thus, parallel development can be considered a counterpart
      to parallel evolution. Specific macromolecular interactions leading to the
      regulation of the c-fos gene are given as an example of a "controller node"
      defined as a regulatory unit. Quantitative changes in gene control are
      distinguished from relational changes, and frequent parallelism in quantitative
      changes is noted in Drosophila enzymes. Evolutionary reversions in quantitative
      gene expression are also expected. The evolution of relational patterns is
      attributed to several distinct mechanisms, notably the shuffling of protein
      domains. The growth of such patterns may in part be brought about by a particular
      process of compensation for "controller gene diseases," a process that would
      spontaneously tend to lead to increased regulatory and organismal complexity.
      Despite the inferred increase in gene interaction complexity, whose course over
      evolutionary time is unknown, the number of homology groups for the functional
      and structural protein units designated as domains has probably remained rather
      constant, even as, in some of its branches, evolution moved toward "higher"
      organisms. In connection with this process, the question is raised of parallel
      evolution within the purview of activating and repressing master switches and in
      regard to the number of levels into which the hierarchies of genic master
      switches will eventually be resolved.

PMID- 7807558
TI  - Excellence in medicine: 100 years of caring. Inaugural Address.

PMID- 7807557
TI  - HIV infection: what difference have we made on the course of the disease and
      where do we go from here?

PMID- 7807560
TI  - Research issues in the study of very low birthweight and preterm delivery among
      African-American women.
AB  - Very low birthweight and preterm delivery explain two thirds of the excess deaths
      experienced by African-American infants. Although comprehensive, good quality
      services for all African-American women will help to reduce the twofold higher
      rate of infant mortality experienced by African-American infants compared with
      white infants, the infant mortality gap will not be closed until prevention
      research is conducted that incorporates the social, cultural, and political
      context of life for African-American women; the environmental stressors and the
      physiologic responses associated with stress; and the protective mechanisms
      available in the community for responding to stress. Discrimination may be an
      important stressor that influences a woman's susceptibility to a poor pregnancy
      outcome. Strategies already exist in the community to cope with discrimination
      and other environmental stressors. To capture the effects of discrimination and
      other environmental factors and the protective factors important for prevention,
      the research approach must involve African-American women and their communities
      as collaborators in the research. Such collaboration will help to avoid problems
      with scientific racism.

PMID- 7807559
TI  - What is the significance of black-white differences in risky sexual behavior?
AB  - A sample of African-American and white young adults were classified as having
      multiple sex partners or one sexual partner. Subjects with multiple sexual
      partners were more likely to use drugs and practice risky sexual behaviors such
      as having anal intercourse, having sexual experiences with a prostitute, and
      having a history of gonorrhea (P < .001) and genital warts (P < .01). Additional
      analyses were conducted to determine African-American versus white differences in
      risky sexual behaviors. Results indicated that whites in the multiple partners
      and single partner groups were more likely to engage in anal and oral sex, while
      African Americans were more likely to have sex with prostitutes. Attitudes about
      the use of condoms differed significantly by multiple partner status (P < .004)
      and gender (P < .007), but not ethnicity. However, angry reactions about the use
      of condoms occurred more with African Americans (P < .003) and males (P < .05)
      than with whites or females. While whites reported a greater use of drugs and a
      significantly higher level of knowledge about HIV/AIDS, African Americans
      reported a significantly greater perception of risk for being exposed to human
      immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) (P < .01)
      and significantly more gonorrhea (P < .10), syphilis (P < .05), and HIV/AIDS (P <
      .05). No whites in our sample were treated for syphilis nor had they tested
      positive for HIV/AIDS. On the other hand, 4.5% of the total sample of African
      Americans reported testing positive for HIV/AIDS. Finally, the results from
      discriminant analysis indicate that a large number of variables significantly
      discriminate between subjects who engage in risky sexual behaviors and those who
      do not. Although there is some similarity in the variables for African Americans
      and whites, there was tremendous variability between the ethnic groups in the
      factors that predict risky behaviors. These findings are discussed with reference
      to the need to develop HIV/AIDS prevention programs for African Americans that
      are based on data derived from African-American populations rather than from
      black versus white comparison studies.

PMID- 7807561
TI  - Common emergencies in cancer medicine: infectious and treatment-related
      syndromes, Part I.
AB  - This two-part article, the last in a series of articles on cancer emergencies,
      summarizes the common medical emergencies that can occur as a result of
      infectious processes (Part I) and antitumor treatment secondary to chemotherapy,
      biological response modifiers, or radiotherapy (Part II). The use of high-dose
      cytotoxic agents, coupled with the common instillation of indwelling central
      venous access devices, have altered the spectrum of infectious etiologies that
      are appreciated in clinical practice. In addition, a myriad of cytotoxic agents
      and radiotherapeutic treatment schemes are used widely in clinical oncologic
      practice. While most of their related side effects are not considered life
      threatening emergencies, they can be fatal if not recognized early and treated
      promptly. Moreover, some of these infectious and treatment-related sequelae can
      be prevented.

PMID- 7807562
TI  - Side effects and complications of treatment with desmopressin for enuresis.
AB  - A literature search revealed 23 studies that have reported on the type or
      frequency of side effects or complications associated with the use of
      desmopressin (DDAVP, Rhone-Poulenc Rorer Pharmaceuticals Inc, Collegeville,
      Pennsylvania) for the treatment of enuresis. Thirty-one (4.3%) side effects were
      reported in 717 patients. Seizure secondary to water intoxication is a potential
      complication of treatment with desmopressin and was reported in six patients,
      usually in association with excess fluid intake during the evening or day
      preceding the use of desmopressin. Desmopressin appears to have a favorable
      safety profile. Patients should be specifically instructed not to ingest excess
      fluids during the evening prior to administration of desmopressin.

PMID- 7807563
TI  - Electron microscopic findings in hepatic allograft rejection.
AB  - Orthotopic liver transplantation is today an accepted surgical procedure for
      patients with irreversible, end-stage liver disease. Between 1988 and 1993, seven
      patients (one patient twice) received liver grafts for end-stage liver disease at
      Howard University Hospital, Washington, DC. In conjunction with the transplant
      procedure, a total of 32 liver needle biopsy specimens were submitted to the
      pathology department. Almost half of all liver graft failures are attributed to
      acute, or in a lesser degree, to chronic rejection. The purpose of this study was
      to describe the ultrastructural findings in acute cellular rejection and to
      correlate the ultrastructure with the histology. The key ultrastructural features
      of acute cellular rejection were: a mixed cellular inflammatory infiltrate in the
      portal tract, bile duct damage by immunocytes with reduplication of the
      epithelial basement membrane, endotheliitis, and intramitochondrial crystalline
      inclusions. It was concluded that electron microscopic investigation
      significantly contributes to better understanding the immunopathologic mechanism
      underlying liver allograft rejection.

PMID- 7807564
TI  - Yersinia enterocolitica sepsis in a 3-week-old child.
AB  - Yersinia enterocolitica has been described with increasing frequency in the
      United States. Commonly, Y enterocolitica is a self-limiting gastrointestinal
      disorder, but occasionally it can lead to fulminant infection. This case report
      describes a 3-week-old male who succumbed to Y enterocolitica sepsis and reviews
      the literature.

PMID- 7807565
TI  - Historical aspects of minorities and the health professions.

PMID- 7807566
TI  - Restricting parents' visits to children hospitalized for abuse or neglect: a
      survey.

PMID- 7807567
TI  - More on health, wealth, and hygiene.

PMID- 7807568
TI  - Cultural sensitivity and health care.

PMID- 7807569
TI  - African-American health-care reform essentials: business and economic
      implications.

PMID- 7807570
TI  - Religious involvement and health status among African-American males.
AB  - Previous studies document the importance of religious involvement in African
      American communities. This study examines the extent to which religious
      involvement is associated with health status among African-American males. The
      data come from a community sample of 537 males residing in a major US urban area.
      Three indicators of religious involvement were used: denominational affiliation,
      frequency of church attendance, and overall religiosity. Measures of health
      status included a self-assessment of physical health, depressive symptoms, self
      reported hypertension, cigarette smoking, and daily drinking of alcohol. The
      results show significant associations between selected indicators of religious
      involvement and measures of health status. Fewer depressive symptoms are
      associated with having a denominational affiliation, while no or low frequency of
      church attendance is associated with current smoking and daily drinking.
      Implications for health-related interventions with African-American males are
      discussed in light of these findings.

PMID- 7807571
TI  - Effects of pretreatment transurethral resection on survival in prostatic
      carcinoma.
AB  - The survival of 117 patients with carcinoma of the prostate treated with
      radiation at SUNY-Health Science Center at Brooklyn and Kings County Hospital
      Center was analyzed according to their pretreatment method of diagnosis. Sixty
      four patients (54.7%) underwent a transurethral resection of the prostate (TURP)
      for obstructive symptoms prior to definitive therapy, while 53 patients (45.3%)
      were diagnosed with needle biopsy. The overall 5-year survival rate was 46% in
      the needle biopsy group and 38% in the TURP group. Black and white patients with
      high Gleason scores (7 to 10) and black patients with low-grade tumors who
      underwent TURP had an adverse 5-year survival rate compared with those patients
      diagnosed by needle biopsy. The 5-year survival rate of patients with high
      Gleason scores comparing needle and TURP was 37% versus 16%. The 5-year survival
      rate of black patients with low-grade tumors comparing needle biopsy versus TURP
      was 50% and 22%, respectively, although not statistically significant because of
      the small sample size. When evaluated by stage, there was no difference in
      survival rates of TURP versus needle biopsy. Black patients who underwent TURP
      had a 28% 5-year survival rate compared with a 44% 5-year survival rate in white
      TURP patients. This analysis reveals that black and white patients with high
      grade tumors and black patients, even with low-grade tumors, may have a lower
      survival rate if they undergo TURP prior to radiation, but this may be due to
      higher stage and larger volume disease in these patients.

PMID- 7807573
TI  - The health-care system and African Americans in Indianapolis.
AB  - In order to critically assess the health-care system in Indianapolis, it is
      important to analyze this African-American population from two major
      perspectives. First, the local African-American population must be viewed in the
      context of the local health-care system in its present and historical setting.
      Second, the local African-American population must be viewed in conjunction with
      other urban African-American populations. These two perspectives will show how
      the region's economic, social, cultural, and political climate have affected the
      health-care status of African Americans in Indianapolis.

PMID- 7807574
TI  - Intermediate variables as determinants of adverse pregnancy outcome in high-risk
      inner-city populations.
AB  - A probability sample survey of high-risk inner-city women with a live birth in
      the last 3 years shows that maternal medical risks and health behaviors during
      pregnancy are important intermediate variables influencing preterm delivery and
      birthweight. Women who developed two or more medical risks had about three-and-a
      half times the risk of preterm delivery and two-and-a-half times the risk of low
      birthweight compared to those without such risks. Women with prior fetal loss had
      twofold increase in the risk of preterm delivery and low birthweight. Unintended
      pregnancy resulted in one-and-a-half to twofold increase in preterm delivery and
      low birthweight, respectively. Inadequate gestational weight increased the risk
      of preterm delivery by about 50%. Smoking during pregnancy raised the risk of low
      birthweight slightly more than one-and-a-half times.

PMID- 7807572
TI  - Common emergencies in cancer medicine: infectious and treatment-related
      syndromes, Part II.
AB  - This article completes a summary of the common medical emergencies that can occur
      as a result of infectious processes (Part I) and antitumor treatment secondary to
      chemotherapy, biological response modifiers, or radiotherapy (Part II). The use
      of high-dose cytotoxic agents, coupled with the common instillation of indwelling
      central venous access devices, have altered the spectrum of infectious etiologies
      that are appreciated in clinical practice. In addition, a myriad of cytotoxic
      agents and radiotherapeutic treatment schemes are used widely in clinical
      oncologic practice. While most of their related side effects are not considered
      life-threatening emergencies, they can be fatal if not recognized early and
      treated promptly. Moreover, some of these infectious and treatment-related
      sequelae can be prevented. This article highlights some of these clinical
      observations.

PMID- 7807575
TI  - Pediculosis capitis among urban school children in Ilorin, Nigeria.
AB  - A survey of 6882 primary school children living in Ilorin, Nigeria revealed that
      3.7% of the children were infested with Pediculus humanus capitis. Infestation
      rate among the children in the Islamic community was 4.1%, whereas in the
      Christian area, the infestation rate was 3%. Girls had a higher infestation rate
      (5.6%) than boys (2.1%). The highest infestation rate (28.4%) was observed among
      girls of low socioeconomic class, followed by their male counterparts (11.2%).
      Factors associated with the onset of pediculosis included overcrowding, long
      hair, family size, age, living in a sordid environment, and personal hygiene.
      Strategies for the effective control of pediculosis are discussed.

PMID- 7807576
TI  - Delayed postoperative hemorrhage complicating chalazion surgery.
AB  - Chalazion surgery is a common minor ophthalmic surgical procedure used to treat
      chalazia after conservative measures have failed. Complications are infrequent
      and generally easily managed with minimal morbidity. This article presents an
      atypical case of an elderly woman with a history of hypertension who experienced
      sudden profuse hemorrhaging 10 days after chalazion surgery. The clinical
      findings are presented along with a brief overview of the relevant vascular
      anatomy of the eyelid and a discussion of possible etiologic factors.

PMID- 7807577
TI  - The relation of acute intestinal diseases to lesions of the liver. 1909.

PMID- 7807578
TI  - Neurological mouse mutants and the genes of myelin.
AB  - The prospect to create mouse mutants of virtually any cloned gene has renewed
      interest in the genetic analysis of mammalian brain development. A diverse group
      of spontaneous and engineered mouse mutants, characterized by a defect of myelin
      formation, has been intensively studied from the morphological to the molecular
      level. In this system, genetics has been successfully applied to analyze a
      corresponding set of membrane proteins which help to elaborate a defined
      structural entity, compact myelin. Shiverer, jimpy, Trembler, and protein zero
      (P0)-deficient mice demonstrate the overall function of myelination and have
      become models for human neurological diseases. They also illustrate some of the
      problems encountered in defining protein functions from complex mutant
      phenotypes.

PMID- 7807579
TI  - Resolving three types of chloride channels in demyelinated Xenopus axons.
AB  - Axons from Xenopus sciatic nerve were demyelinated by intraneural injection of
      lysolecithin rendering the entire internodal axolema accessible to a patch
      electrode. In this region, three types of anion selective pores were found and
      characterized at the single-channel level. These included outwardly rectifying,
      inwardly rectifying, and maxi Cl- channels. The outwardly rectifying Cl- channels
      (24 pS) are activated by depolarization with a weak voltage dependence of 42 mV
      per e-fold change in open probability. The inwardly rectifying Cl- channels (27
      pS) are insensitive to voltage, but can be blocked by internal application of 100
      microM SITS or DIDS. The I-V curves of rectifying channels are S-shaped and can
      be fitted by a kinetic model with a single free energy barrier. The rectification
      may be related to the location of this barrier. The maxi Cl- channel (335 pS) is
      often open at the resting potential, but is inactivated by a large
      depolarization. The rectification, voltage dependence, and inactivation of these
      channels may contribute to the regulation of axonal Cl- balance and resting
      potential.

PMID- 7807580
TI  - Expression of the intermediate filament-associated protein related to beta
      amyloid precursor protein is developmentally regulated in cultured cells.
AB  - It was previously reported that a monoclonal antibody to beta-amyloid precursor
      protein (mab22C11; Boehringer Mannheim, Indianapolis, IN) labels an intermediate
      filament-associated protein (beta APP-IFAP) in cultured human skin fibroblasts
      (Dooley et al.: J Neurosci Res 33:60-67, 1992). The time course of its expression
      and association with different classes of intermediate filaments has been
      assessed in neurons, Schwann cells, and astrocytes in dissociated cultures of
      murine brain and spinal cord-dorsal root ganglia; in primary cultures of human
      muscle; and in the epithelial cell line PtK1. beta APP-IFAP was expressed in all
      non-neuronal cell types examined. Mab22C11 immunoreactivity was minimal or absent
      following dissociation or subculture, but gradually increased with time. In
      fibroblasts, myoblasts, and epithelial cells, the distribution eventually
      resembled that of vimentin. With the exception of glial fibrillary acidic protein
      (GFAP), beta APP-IFAP was not associated with the intermediate filament proteins
      characteristically found in differentiated cells, i.e., desmin, the cytokeratins,
      and neurofilament proteins. No labeling of neurons by mab22C11 was observed at
      any stage of in vitro maturation. In sections of Alzheimer's brain, the antibody
      labeled a subpopulation of reactive astrocytes. It is suggested that beta APP
      IFAP may be the product of a member of the beta APP multigene family expressed
      developmentally in non-neuronal cells.

PMID- 7807581
TI  - Fluid-phase endocytosis of horseradish peroxidase by cerebral endothelial cells
      in primary culture: characterization and kinetic analysis.
AB  - Endocytosis of horseradish peroxidase (HRP) was studied in primary cultures of
      cerebral endothelial cells prepared from 2-week-old rats. These cultures were
      considered "endothelial-like" on the basis of their ability to internalize
      acetylated low density lipoprotein. Cellular localization of HRP protein was
      examined at the light and ultrastructural levels and endocytosis of the protein
      was evaluated by a colorimetric assay. HRP was localized in discrete cytoplasmic
      granules by light microscopy. At the ultrastructural level these granules
      corresponded to pleomorphic membrane-bound structures that were present
      throughout the cytoplasm. The amount of internalized HRP was directly related to
      the concentration of the protein in the medium, was not saturable at high
      concentrations of HRP, and increased with time. Endocytosis proceeded at 37
      degrees C, but was abolished at 4 degrees C. In pulse-chase experiments, the
      quantity of internalized protein in the cells did not significantly change during
      the 2 hr chase period. Taken together, these findings suggest that
      internalization of HRP occurs by fluid-phase endocytosis, a non-receptor-mediated
      process, and that the protein is stable within an intracellular compartment for
      at least several hours.

PMID- 7807582
TI  - Presence of axonal paired helical filament-tau in Alzheimer's disease:
      submicroscopic localization.
AB  - While normal adult tau protein is found typically in axons, paired helical
      filament (PHF) tau has been shown immunohistochemically to be in the
      somatodendritic compartment in Alzheimer's disease (AD). The small amount of PHF
      tau (8-11%) found in white matter with immunochemical methods is shown here by
      immunoelectron microscopy to be located in axons. It is localized to straight
      filament variants of PHFs. The small amount of PHF-tau in white matter,
      therefore, appears not to result from the contamination of immunochemical
      preparations but to be an integral constituent of affected axons in AD.

PMID- 7807583
TI  - Characterization of proteoglycans synthesized by murine embryonal carcinoma cells
      (P19) reveals increased expression of perlecan (heparan sulfate proteoglycan)
      during neuronal differentiation.
AB  - Proteoglycans (PGs) incorporated into cell layer and secreted into media were
      characterized during retinoic acid-induced neuronal differentiation of cultured
      P19 murine embryonal carcinoma cells. Heparan sulfate significantly increased (P
      < 0.01) in cell layer following neuronal differentiation of P19 cells by 3.9
      fold. CL-4B gel chromatography revealed the major PGs present in cell layer of
      stem cells eluted as a broad peak with a Kav = 0.65, and was susceptible to
      chondroitin ABC lyase. The chondroitin ABC lyase resistant material eluted as a
      broad peak between Kav = 0.40 and Kav = 0.60, and was only partially digested
      with heparitinase/heparinase (with resistant material eluting at Kav = 0.70).
      Therefore, the cell layer of stem cells contained primarily chondroitin
      sulfate/dermatan sulfate (CS/DS) PGs, with lesser amounts of heparan sulfate
      proteoglycans (HSPGs). This was confirmed by SDS-PAGE. The CS/DS PGs in the cell
      layer of stem cells had an apparent M(r) of approximately > 200 kDa, and the
      HSPGs had an apparent M(r) of approximately 140-230 kDa. In contrast, the major
      PGs in the cell layer of neurons consisted primarily of HSPGs, with only a minor
      proportion of CS/DS PGs. Furthermore, both gel filtration chromatography and SDS
      PAGE analysis revealed a larger HSPG in the cell layer of neurons (Kav = 0.3-0.6
      on CL-4B following chondroitin ABC lyase digestion; M(r) 170 kDa- > 400 kDa on
      SDS-PAGE) in comparison to stem cells (Kav = 0.4-0.6 on CL-4B following
      chondroitin ABC lyase digestion; M(r) 140-230 kDa on SDS-PAGE). Likewise, the
      major PGs secreted into media of stem cells consisted almost exclusively of CS/DS
      PGs, with lesser amounts of HSPGs, whereas an increase in HSPGs in the media of
      neurons was apparent. Western, Northern, and immunocytochemical analysis
      demonstrated that mRNA transcript and protein levels for a specific HSPG (i.e.,
      perlecan) markedly increased in cell layer following P19 neuronal
      differentiation. Perlecan core protein was identified by Western blot analysis
      using specific monoclonal and polyclonal antibodies, as a large HSPG with a core
      protein of apparent M(r) approximately 370-400 kDa, and was observed primarily in
      extracts from neurons. Northern blot analysis with a cDNA to perlecan revealed a
      significant (P < 0.01) 12.7-fold increase in expression of perlecan in neurons
      (day 9) in comparison to stem cells. The increase in perlecan message during P19
      neuronal differentiation was concomitant with a significant (P < 0.01) 26.3-fold
      increase in message for beta-amyloid precursor protein (beta PP).(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7807584
TI  - Human fetal neurons in culture: intercellular communication and voltage- and
      ligand-gated responses.
AB  - We established high density primary cultures of neural cells from dissociated
      second trimester human fetal brains using a novel spin seeding method. Under our
      culture conditions, the majority of the cells exhibited neuronal phenotypes as
      evidenced by morphological criteria, immunoreactivity to the 66 kDa neurofilament
      protein and expression of TTX-sensitive Na+ channels and cell excitability. These
      cultures were enriched in glutamic acid decarboxylase (GAD), the synthetic enzyme
      of the neurotransmitter GABA, and responded with Ca2+ influx to acute application
      of glutamate. Interestingly, the human fetal neurons in culture did not express
      either dopaminergic or cholinergic phenotypes. In addition, the population of
      neurons obtained express a high incidence of gap junction-mediated intercellular
      communication. These studies provide evidence that functional neuronal properties
      arise early during prenatal development in humans and offer the potential to
      evaluate pharmacological agents on primary human neurons.

PMID- 7807585
TI  - Human neurocytoma cells in culture show characteristics of astroglial
      differentiation.
AB  - Cultured human neurocytoma cells from two neurosurgical patients were analysed
      for their immunocytochemical staining patterns and growth characteristics. In
      both cases, the cells stained positive for glial acidic fibrillary protein (GFAP)
      within one day of tissue culture in medium, with and without fetal calf serum,
      whereas the histological tumor specimens were negative. Both cases contained
      cells concomitantly expressing GFAP and synaptophysin (SNP) in the primary
      cultures. Epidermal growth factor (EGF) was mitogenic for the cultured cells but
      not platelet derived growth factor alpha (PDGF AA) or nerve growth factor (NGF).
      It is concluded that the human neurocytomas may represent neoplasms of a
      pluripotent neuroglial cell which can provide an interesting model to study the
      determinants for human glial/neuronal differentiation in vitro.

PMID- 7807586
TI  - Identification and characterization of Batk, a predominantly brain-specific non
      receptor protein tyrosine kinase related to Csk.
AB  - A novel cDNA, brain-associated tyrosine kinase (Batk), was isolated from a rat
      hippocampal library and appears to encode a new member of the Csk subfamily of
      non-receptor protein tyrosine kinases, with 52% overall amino acid identity to
      rat Csk. Batk resembles kinases of the Src family in that it contains a Src
      homology 2 (SH2) domain and an SH3 domain, followed by a tyrosine kinase domain.
      Analysis of incompletely spliced Batk cDNAs suggests that the genomic structure
      of Batk is similar to that of Csk with identical exon/intron boundaries. Batk
      also shows significant homology (86% overall amino acid identity) to the recently
      described human megakaryocyte-specific Matk. Although Batk is 41 amino acids
      shorter than Matk, Southern blot analysis suggests that Batk might be a rat
      homolog of Matk. Batk is predominantly expressed in the brain, with lower
      expression in the spleen and undetectable expression in other tissues. In situ
      hybridization and Northern blot analysis show that Batk is widely distributed
      throughout the adult brain, being primarily expressed in neurons, including those
      of the hippocampus and cortex. In contrast, embryos appear to have markedly
      decreased expression levels. Analysis of postnatal day 1 brain suggests that Batk
      may be upregulated at birth throughout the brain except in the cerebellum. In
      view of its homology to Csk, a negative regulator of Src family tyrosine kinases,
      and its generalized expression in the adult brain, we suggest that Batk may
      function as a brain-specific regulator of kinases involved in the development and
      maintenance of the nervous system.

PMID- 7807587
TI  - G-protein gamma 7 subunit is selectively expressed in medium-sized neurons and
      dendrites of the rat neostriatum.
AB  - We used subtractive hybridization to isolate clones of gamma 7, a 68 residue G
      protein gamma subunit. Northern blotting and in situ hybridization reveal that
      the gamma 7 subunit mRNA is expressed primarily in medium-sized neurons of the
      neostriatum and nucleus accumbens and neurons of the olfactory tubercle, and at
      low levels in the dentate gyrus of the hippocampal formation and laminae II-III,
      and V of the neocortex. The gamma 7 mRNA is translocated into dendrites of
      neurons in the neostriatum and the dentate gyrus of the hippocampus. gamma 7 is
      expressed at relatively very low concentrations in peripheral tissues. The
      selective pattern of gamma 7 expression within the brain is highly reminiscent of
      those of the striatum-enriched adenylyl cyclase ACST, dopamine receptors, and the
      alpha subunit of G(olf), suggesting that, in striatum, gamma 7 may be a subunit
      of a G(olf) alpha-containing G protein that couples dopamine receptors
      selectively to ACST.

PMID- 7807589
TI  - Long-term effects of deprivation of cell support in the distal stump on
      peripheral nerve regeneration.
AB  - The distal stump of an injured peripheral nerve supports regenerating axons by
      offering a favourable growth substratum and several cell-produced growth factors.
      Deprivation of cellular factors alone has been shown not to prevent fairly rapid
      axonal elongation after nerve injury if the growth substratum was preserved. The
      present study examined possible long-term untoward effects of cell support
      deprivation during an early phase of nerve regeneration. Rat sciatic nerve was
      crushed and a 25 mm long distal nerve segment was made acellular by freezing
      thawing, while the integrity of the growth substratum for the regenerating axons
      was preserved. Toe-spreading reflex and skin sensitivity to pinch in the foot
      were monitored to follow recovery of motor and sensory function, respectively.
      The number of myelinated axons was determined in the sciatic nerve proximally to
      the lesion site, and distally in the predominantly sensory sural nerve as well as
      in the mixed motor nerve to the soleus muscle. Except for a short delay in the
      onset of recovery, explainable by the reduced elongation rate of axons growing
      through the acellular nerve segment, we found no deleterious effect of cell
      support deprivation on sensory or motor function recovery after nerve crush. Most
      of regenerating sensory neurons did not critically depend on the distal stump
      cell support. However, a 15% and 25% loss of myelinated axons both proximally to
      the lesion and distally in the sensory sural nerve, respectively, indicated that
      a corresponding minor loss of injured sensory neurons occurred when they were
      deprived of such cell support even if provided with a favourable growth
      substratum for successful regeneration.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7807588
TI  - Dopamine transporter mediated release of dopamine: role of chloride.
AB  - Using a rapid (0.5 ml/min) flow rate superfusion system, the dopamine (DA)
      transporter mediated release of DA is further explored, and compared to the
      depolarization evoked release of DA in rat striatal synaptosomes preloaded with
      radioactive DA (3H-DA). In this system external DA in the low microM range
      efficaciously releases the preloaded transmitter, the maximal response being
      reached at 3 microM DA. The external DA stimulated release is Ca(2+)-independent,
      Cl(-)-dependent, and blocked by both bupropion and nomifensine. The atypical
      antidepressant bupropion inhibits 3H-DA accumulation to rat striatal synaptosomes
      with a calculated IC50 of 1.3 x 10(-6) M. Among DA uptake blockers some are known
      to act as DA releasing agents. Here we found that the DA uptake blocker
      nomifensine (30 microM) is unable to modify the baseline release of 3H-DA,
      whereas bupropion (10 microM) clearly elevates the baseline release of 3H-DA in a
      Ca(2+)-independent and Cl(-)-dependent manner. The non releasing agent
      nomifensine blocks the release of 3H-DA induced by bupropion. The Ca(2+)
      dependent, high K+ depolarization evoked release of 3H-DA is not modified by
      nomifensine and does not depend on the external Cl- concentration. When the
      depolarizing medium contains DA the carrier mediated release of 3H-DA induced by
      the external DA is additive to the high K+ induced response. A drastic drop in
      the external Cl- concentration induces 3H-DA release. This release of 3H-DA
      induced by low external Cl- levels is completely blocked by nomifensine, which
      only slightly diminished the release of 3H-DA induced by the absence of external
      Na+. On the basis of these results, it is concluded that: 1) Rapid perfusion flow
      rates eliminate DA reuptake. 2) DA uptake inhibitors either with or without DA
      releasing capabilities block the release of DA induced by microM levels of
      external DA. 3) By preventing translocation of the DA transporter mobile moiety,
      nomifensine may inhibit the release of DA induced by external DA or bupropion and
      by drastic drops in the external Cl- concentration. 4) In the absence of
      nomifensine, the DA transporter works under both resting and depolarized
      conditions, but in contrast to the GABA transporter (Sitges et al.: Neurochem Res
      18:1081-1087, 1993), the DA transporter does not contribute to the amount of the
      DA released by depolarization. 5) Reversal of the DA uptake carrier is favored by
      conditions increasing the internal DA levels. 6) Cl- rather than Na+ is a major
      determinant in 3H-DA movements through the DA transporter.

PMID- 7807590
TI  - Fever and feeding in the rat: actions of intrahypothalamic interleukin-6 compared
      to macrophage inflammatory protein-1 beta (MIP-1 beta).
AB  - The chemokines, macrophage inflammatory protein-1 (MIP-1) and its subunit MIP-1
      beta, induce an intense fever in the rat when they are injected directly into the
      anterior hypothalamic, pre-optic area (AH/POA), a region containing
      thermosensitive neurons. The purpose of this study was to compare the central
      action on body temperature (Tb) of MIP-1 beta with that of interleukin-6 (IL-6),
      which also has been implicated in the cerebral mechanism underlying the
      pathogenesis of fever. Following the stereotaxic implantation in the AH/POA of
      guide cannulae for repeated micro-injections, radio transmitters which monitor Tb
      continuously were inserted intraperitoneally in each of 15 male Sprague-Dawley
      rats. Each micro-injection was made in a site in the AH/POA in a volume of 1.0
      microliter of pyrogen-free artificial CSF, recombinant murine MIP-1 beta, or
      recombinant human IL-6. MIP-1 beta in a dose of 25 pg evoked an intense fever
      characterized by a short latency, a mean maximum rise in Tb of 2.4 +/- 0.21
      degrees C reached by 3.7 +/- 0.42 hr, and a duration exceeding 6.5 hr. Injected
      into homologous sites in the AH/POA, IL-6 induced a dose dependent fever of
      similar latency and a mean maximal increase in Tb of 1.2 +/- 0.25 degrees C, 1.8
      +/- 0.15 degrees C, and 2.1 +/- 0.22 degrees C and duration of 6.2 +/- 1.28 hr,
      6.7 +/- 0.49 hr, and 6.8 +/- 0.65 hr when given in doses of 25, 50, and 100 ng,
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7807591
TI  - Poly(ADP-ribose) polymerase: early involvement in glutamate-induced neurotoxicity
      in cultured cerebellar granule cells.
AB  - Glutamate neurotoxicity is correlated with an increase of cytosolic free Ca2+. In
      some cell systems, activation of Ca2+ dependent endonucleases or formation of
      free radicals can damage DNA and activate the chromatin bound enzyme poly(ADP
      ribose) polymerase (pADPRP). We have investigated whether pADPRP may be involved
      in glutamate neurotoxicity in vitro. Cerebellar granule cells at 12 days in
      culture when treated with a toxic dose of glutamate (100 microM) showed a rapid
      and transient increase of polyADP-ribose immunoreactivity. Cellular
      immunostaining was heterogeneous and returned to control levels after washout of
      glutamate. In the same cell preparations glutamate elicited a marked increase in
      enzyme protein immunoreactivity which persisted at later times. Non-toxic doses
      of glutamate did not affect immunostaining. In another set of experiments, pADPRP
      mRNA was increased 30 min after glutamate. In order to investigate the role of
      pADPRP in glutamate-mediated neurotoxicity, structurally different inhibitors of
      pADPRP (3-aminobenzamide, benzamide,3-aminophthalhydrazide) and their inactive
      analogues (benzoic acid and phthalimide) were tested in this model. Addition of
      the inhibitors to cultures 60 min before and during the 30 min of glutamate
      treatment prevented neuronal death by 60-100%, assessed 24 hr later. Glutamate
      induced Ca2+ influx was not affected. Inactive analogues failed to afford
      neuroprotection. These data indicate that not only is pADPRP activated by the
      early, possibly Ca(2+)-mediated mechanisms initiated by glutamate, but that it
      might also actively contribute to the subsequent neuronal death.

PMID- 7807592
TI  - Immortalization of immature and mature mouse astrocytes with SV40 T antigen.
AB  - The ability of neonatal astrocytes to promote neurite outgrowth in vitro and in
      vivo diminishes as astrocytes mature. This property correlates with the
      developmental loss of the central nervous system's ability to regenerate after
      injury. Cell lines representative of immature and mature astrocytes would be
      useful for studies to determine differences between these two populations.
      Previous work on immortalization of bipotential neural/glial precursors and fully
      differentiated glial cells suggests that immortalization of astrocytes at timed
      intervals of culture may yield cell lines trapped in different maturation states.
      To test this, neonatal mouse cortical astrocytes were immortalized by retrovirus
      mediated transfer of the SV40 T antigen (Tag) gene at 2, 6 and 17 days of
      culture. The clonal cell lines express Tag and are contact-inhibited. Three
      phenotypes that change as a function of astrocyte maturation were examined to
      determine the fidelity with which the cell lines represent immature and mature
      astrocytes. These were: (1) cell morphology, growth pattern and size, (2) level
      of glial fibrillary acidic protein (GFAP) expression, and (3) neurite outgrowth
      promotion. First, immature and mature lines resemble mortal type 1 astrocytes of
      corresponding ages with respect to morphology and growth pattern, and retain a
      quantitative difference in cell size (mature cells are larger). Second, the
      pattern of GFAP expression is preserved, with immature lines expressing lower
      levels than mature cell lines, but the overall GFAP levels are significantly
      lower in immortalized cell lines compared to mortal cells. Finally, promotion of
      neurite outgrowth from embryonic chick retinal ganglion cells on monolayers of
      the cell lines was examined. While all neurite outgrowth measures are
      significantly greater for the immortalized lines than for control 3T3 cells, they
      are attenuated relative to mortal astrocytes. The age-related pattern of stronger
      outgrowth support on immature astrocytes is retained for neurite initiation, but
      not retained for mean neurite length. Thus, SV40 Tag-immortalized astrocytes have
      a complex phenotype characterized by retention of age-related differences in
      morphology, growth pattern and cell size, and by a marked attenuation of some
      astrocyte-specific characteristics but retention of age-related differences in
      the expression level of these same characteristics, and finally, loss of the
      ability to support neurite extension at level characteristic of immature
      astrocytes.

PMID- 7807593
TI  - Decreased synaptic density in aged brains and its prevention by rearing under
      enriched environment as revealed by synaptophysin contents.
AB  - Changes in synaptic density in various brain regions were assessed among
      different age groups of rats maintained in ordinary small cages, as determined by
      synaptophysin assay. The synaptophysin content in hippocampus decreases as early
      as in the adult stage. The most remarkable decrement occurs in occipital cortex.
      In other regions, synaptophysin contents decrease in senescence to 60-77% of the
      respective peak values during young and adult stages. The other rat group reared
      under enriched environment in a large cage until 30 months of age was examined
      for synaptic density, and was revealed to maintain the similar levels as in
      young, or even higher levels in frontal, temporal, entorhinal cortices and
      hippocampus. These results indicate that the synaptic density in cerebrum
      decreases in senescence and this decrease can be prevented by rearing under
      enriched environment.

PMID- 7807594
TI  - Protein kinase C in cultured adult human oligodendrocytes: a potential role for
      isoform alpha as a mediator of process outgrowth.
AB  - The extension of cellular processes from the oligodendrocyte soma is an early and
      critical event in myelin formation. Previous reports from this laboratory have
      implicated a role for protein kinase C (PKC) as an important intracellular
      mediator of this critical step in myelinogenesis. In the current study, the
      regrowth of fibers by adult human oligodendrocytes was examined and was found to
      be significantly enhanced by the PKC stimulator, 4 beta-phorbol-12,13-didecanoate
      (PDB); this was accompanied by a 400-500% increase in oligodendroglial PKC
      activity. In contrast to other cell types, the increased PKC activity in
      oligodendrocytes was not followed by subsequent down-regulation of the enzyme.
      The role of PKC in oligodendroglial process formation was further demonstrated by
      the ability of inhibitors of PKC to block the basal- or PDB-enhanced fiber
      outgrowth. As well, studies employing isoform-specific agonists implicated PKC
      alpha as the major determinant of fiber outgrowth by oligodendrocytes. The
      potential significance of PKC in myelin formation was further underscored by the
      observation that the synthesis of myelin basic protein, a prerequisite component
      for myelinogenesis, was increased by 2-fold in PDB-treated oligodendrocytes.
      Collectively, these observations suggest that PKC, in particular the alpha
      isoform, constitutes an important mediator in the initiation of myelin formation.

PMID- 7807595
TI  - An experimental study on somatostatin receptors in the brains of hepatic
      encephalopathy rats.
AB  - The present study was undertaken to evaluate the effect of somatostatin (SS)
      receptor, a brain-gut peptide receptor which is capable of inhibiting central
      neurons, on the pathogenesis of hepatic encephalopathy (HE). By means of
      radioligand binding assay, SS receptors in crude synaptosomal membrane of rat
      brains were investigated in a rat model of HE induced by partial hepatectomy
      following carbon tetrachloride intoxication and in controls. Binding to SS
      receptor was studied using 125 I-SS as radioligand. Scatchard analysis of binding
      data was linear, yielding a dissociation constant (Kd) of 3.99 +/- 0.22 nmol/L
      and a maximal binding capacity (Bmax) of 238 +/- 14.2 fmol/mg of protein in HE
      rats. Only increased Bmax values were observed (P < 0.005), while the Kd values
      were statistically unchanged (P > 0.50), in HE rats as compared with those in
      controls. The results suggest that the changes of SS receptors in brains play a
      significant role in the pathogenesis of HE. The mechanism of HE induced by the
      alterations of SS receptors in the brains was discussed in this paper.

PMID- 7807596
TI  - The significance of anatomical variations of hepatic artery and multiple arterial
      supplies in embolization of liver tumors.
AB  - A new therapeutic measure-step by step-embolization of every feeding vessel in
      dealing with liver cancer has been proposed on the base of the following criteria
      after reviewing the coeliac and superior mesenteric arteriographies in 100 cases
      of liver cancer. The emphasis is put on: 1. Anatomic variation of hepatic
      arteries. 2. Multiple feeding vessels, and 3. The importance of the presence of
      stenosis after embolization and the formation of collateral circulation.

PMID- 7807597
TI  - Macrophages in degradation of calcium phosphate compound artificial bone: an in
      vitro study.
AB  - The isolated mice peritoneal macrophages in degradation of calcium phosphate
      compound artificial bone--collagen/hydroxylapatite (CHA), hydroxylapatite (HA),
      beta-tricalcium phosphate (TCP) ceramics, have been studied by use of both Ca++,
      P concentration assay in cultured supernatant and scanning electron microscopy
      (SEM). The solubility of Ca++, composition of materials increased more
      significantly when macrophages were inoculated than when macrophages were not
      seeded (P < 0.001), and it was shown that the ground materials were wrapped and
      phagocytized or resorbed extracellularly by macrophages under SEM, suggesting
      that macrophages could mediate the degradation of calcium phosphate compound
      artificial bone by phagocytizing and/or degrading extracellularly.

PMID- 7807599
TI  - The inhibitory effect of radix Salviae miltiorrhizae on hypoxic structural
      remodeling of intra-acinar pulmonary arteries.
AB  - The inhibitory effect of Radix Salviae Miltiorrhizae (RSM) on hypoxic structural
      remodeling of intra-acinar pulmonary arteries (IAPA) was observed by light and
      electron microscopy and morphometry. It was found that RSM can not only dilate
      IAPA and relieve the hypoxic injuries to endothelia cells, but also inhibit the
      active muscularization of IAPA in the hypoxic animals, suggesting that RSM plays
      a very important role in inhibiting structural remodeling of IAPA and pulmonary
      hypertension.

PMID- 7807598
TI  - Effect of diallyl trisulfide on the activation of T cell and macrophage-mediated
      cytotoxicity.
AB  - At high concentration (50 micrograms/ml), diallyl trisulfide (DATS) had an
      inhibitory effect on T cell activation (compared with control group, P < 0.05).
      But at appropriate concentrations (3.125-12.5 micrograms/ml), DATS augmented the
      activation of T lymphocytes by Con A (compared with control group, P < 0.01). The
      augmentation of T cell activation by DATS was related to its inhibitory effect on
      the production of nitric oxide (NO) by macrophages. In a wide range of
      concentrations (1-100 micrograms/ml), DATS can inhibit the production of NO by
      macrophages (P < 0.05, P < 0.01). In addition, DATS can antagonize the inhibition
      of tumor-derived immunosuppressive factors produced by S180 cells and Ehrlich
      ascitic cancer cells on the activation of T cells, and reduce the inhibitory rate
      significantly (P < 0.01). DATS, despite its inhibition of the production of NO by
      macrophages, can significantly enhance the production of hydrogen peroxide (H2O2)
      by macrophages. When macrophages were pretreated with DATS for 24 h, the
      cytotoxicity % of macrophages to three tumor cell lines was significantly higher
      than that in corresponding control group (P < 0.05, P < 0.01). In the presence of
      both DATS and LPS, the cytotoxicity of macrophages was further enhanced so that
      the cytotoxicity % of macrophages to tumor cells was significantly higher than
      either that in the presence of DATS alone or that in the presence of LPS alone (P
      < 0.05, P < 0.01). These results indicate that DATS can augment the activation of
      T cells and enhance the anti-tumor function of macrophage, suggesting that DATS
      may be potentially useful in tumor therapy.

PMID- 7807601
TI  - Effect of Tripterygium Wilfordii on adrenal cortex in rat with adjuvant
      arthritis.
AB  - This paper reports the effects of Tripterygium Wilfordii (TW) on adrenal cortex
      in rats with adjuvant arthritis. Forty rats were divided into 5 groups. Adjuvant
      arthritis (AA) models were made with complete freund's adjuvant (CFA) in groups I
      IV. Each of which was treated with sodium carboxyl methyl cellulose, TW,
      prednisone and cyclophosphamide respectively. The untreated rats allocated to
      group V served as normal controls. The swelling of AA markedly subsided in group
      II, III and IV as compared with group I (P < 0.01), whereas no significant
      differences were noted among groups II, III and IV (P > 0.05). The obviously
      increased plasma corticosterone levels and decreased adrenal ascorbic acid levels
      were observed in group II, whereas decreased plasma corticosterone levels and
      increased adrenal ascorbic acid levels were noted in group III. There was a
      striking contrast between groups II and III. The morphological changes of adrenal
      glands under light microscope revealed hypertrophic adrenal cortices in group II,
      and atrophic adrenal cortices in group III. The above findings suggest that the
      effect of promoting production of corticosteroids may be one of the mechanism by
      which TW can effectively treating autoimmune diseases.

PMID- 7807600
TI  - Experimental studies on immune-complex in situ type glomerulonephritis in rabbits
      treated with mai-luo-tong and natural indigo.
AB  - By injection of C-BSA, immune-complex in situ type glomerulonephritis was
      duplicated in rabbits and treated with Mai-Luo-Tong and natural Indigo. The
      results showed that proteinuria in the treated groups M and Q was decreased. The
      difference between group M and control group is statistically significant (P <
      0.05). Under light and electron microscope, although glomerular basement membrane
      was irregularly thickened and subepithelial dense electron deposited in the
      treated group, but microthrombus, erythrocytes and platelets aggregation and
      leukocytes impaction were not seen within glomerular capillaries. Also in groups
      C, Q, M, mesenteric cell count was 99.40 +/- 18.53, 92.87 +/- 17.89, 66.55 +/-
      7.75 respectively, the M. Q groups are compared with group C, the result is of
      statistical significance (P < 0.05) and there is no apparent glomerular fibrosis
      in the treated groups.

PMID- 7807602
TI  - Inhibitory effects of chlorpheniramine and astemizolum on contraction of isolated
      rat and rabbit uteri induced by oxytocin and PGF2 alpha.
AB  - The contraction of isolated rat and rabbit uteri induced by oxytocin and PGF2
      alpha was markedly inhibited by chlorpheniramine (Chl) and astemizolum (Ast),
      both of which also decreased the resting tension of uteri, and their spontaneous
      contraction. The inhibitory effects of both drugs were dose-dependent. At high
      concentrations, Chl 7.4 x 10(-4) mol/L and Ast 10(-4) mol/L could counteract the
      contraction of the uteri induced by Oxy and PGF2 alpha, and their spontaneous
      contraction as well. They decreased the resting tension to the lower level. The
      mechanism of their non-special relaxed action on uteri could not be completely
      explained only by their H1-receptor blocking action. Whether they act by blocking
      calcium channel or by inhibiting calmodulin (CaM) remains to be further explored.

PMID- 7807603
TI  - Effects of amrinone on cardiac contraction and relaxation in isolated, perfused
      rat heart.
AB  - The effects of amrinone on cardiac contraction and relaxation were assessed in
      isolated, perfused rat hearts. It was found that the left ventricular developed
      pressure (LVDP), dp/dtmax and -da/dtmax did not significantly increase, and the
      time constant (tau) did not markedly shorten with perfusion of low concentration
      (1 nmol/L, 100 nmol/L) of amrinone. The perfusion with higher concentration (1000
      nmol/L) of amrinone reduced LVDP (P < 0.01), dp/dtmax (P < 0.01), -dp/dtmax (P <
      0.01), and prolonged tau (P < 0.05) significantly. It was assumed that amrinone
      has no direct positive inotropic effect, and can not improve cardiac relaxation.
      On the contrary, the cardiac contraction and relaxation will be inhibited at
      higher concentration of amrinone.

PMID- 7807604
TI  - Arachidonic acid metabolism in galactosamine/endotoxin induced acute liver injury
      in rats.
AB  - The changes of the levels of LTC4, PGI2 and TXA2 in the liver tissue in SD rats
      with GaIN/LPS-induced acute liver injury was studied with radioimmunoassay (RIA).
      As a result, 12 h after the administration of GaIN/LPS, serum AST (398 +/- 37 u),
      ALT (565 +/- 43 u) increased (P < 0.001) and the concentration of TXA2 (12,188 +/
      588 pg/g.w.wt) in liver tissue increased significantly (P < 0.001), while the
      content of LTC4 (9713 +/- 3557 ng/g.w.wt) and PGI2(1748 +/- 560 pg/g.w.wt) in
      liver tissue were not obviously changed (P > 0.05) and the inflammatory changes
      of the pathological findings were observed. The improvement of serum ALT (330 +/-
      168 u) (P < 0.05) and AST (273 +/- 124 u) (P < 0.05) and histopathological damage
      was observed after the administration of diethylcarbamazine (DEC), a LTA4
      synthesis inhibitor, the liver TXA2 (12,740 +/- 699) concentration significantly
      increased (P < 0.001), while the levels of LTC4 (8179 +/- 1653) and PGI2 (2320 +/
      630) were not obviously changed. Serum ALT (536 +/- 74 u) and AST (416 +/- 41 u)
      (P > 0.05) levels and histopathology did not change with administration of
      indomethacin, a cyclooxygenase inhibitor, but the liver LTC4 (12,166 +/- 1327)
      contents increased (P < 0.05) and TXA2 (1868 +/- 791) reduced significantly (P <
      0.001). The present study suggests that arachidonic acid metabolism in rats with
      acute liver injury are significantly abnormal. Leukotrienes and thromboxane are
      important inflammatory mediators in the liver injury.

PMID- 7807605
TI  - A newly developed serum-free culture system: clonal growth of human acute
      myelogeneous leukemia (AML) progenitors--a report of 14 AML cases.
AB  - A new serum-free culture (SFC) system for human AML-CFU was established and the
      colony-promoting activity of four recombinant human hematopoietic growth factors
      (rhHGFs) including granulocyte-macrophage colony-stimulating factor (rhGM-CSF),
      interleukin-3 (rhIL-3), erythropoietin (rhEPO) and newly developed stem cell
      factor (rhSCF) were investigated in this SFC system. Under the orthogonal design
      condition, it was found that human AML-CFU presented optimal clonal growth in an
      environment of bovine serum albumin (0.6%), saturated human transferrin (2 x 10(
      6) mol/L), cholesterol (2.8 micrograms/ml), bovine insulin (15 micrograms/ml),
      bovine hemin (0.05 mmol/L), linoleic acid (2.8 micrograms/ml), and IMDM.
      Spontaneously growing colonies were observed in 11 out of 14 cases studied. The
      plating efficiencies obtained by culturing with rhGM-CSF, rhIL-3, and rhSCF were
      0.776 +/- 0.621%, 0.574 +/- 0.510%, and 0.647 +/- 0.543% (mean +/- s),
      respectively. There was one case (M3b) showing no response to all HGFs in both
      SFC ad SCC. The clonal growth of AML-CFU obtained from peripheral blood of the
      patient with M6 was unexpectedly marked. As a whole, the newly designed SFC
      system has been demonstrated to be useful for culture of human AML-CFU from both
      bone marrow and peripheral blood.

PMID- 7807606
TI  - Changes in cardiovascular activity during an increase in biliary tract pressure
      in rabbits.
AB  - In order to study the mechanism of decreased blood pressure caused by an acute
      increase in biliary tract pressure, we observed house rabbit model of self-made
      caecus for changes in cardiovascular function when biliary tract pressure was
      increased. It was found that both the blood pressure and cardiac output evidently
      decreased (P < 0.05) parallelly, and the systolic pressure decreased more
      markedly than diastolic pressure. At the same time there was fluctuation in heart
      rate and in central venous pressure; but there was no significant difference
      between them (P > 0.05), suggesting that in the absence of infective agents, the
      increased biliary tract pressure can bring about a decrease in cardiac output,
      which is an important factor contributing to an early blood pressure decrease in
      acute cholangitis of severe type (ACST).

PMID- 7807607
TI  - Clinical application of SPECT to the localization of corticoepileptogenic focus
      of intractable epilepsy.
AB  - This paper presented 51 cases of intractable epilepsy, of which 36 were males,
      and 15 females, with a mean age of 21. They were all verified through CT/MRI,
      among which 17 were proved to have lesions on the brain, and 34 to have no
      lesion. Before operation all the patients were identified by SPECT and cerebral
      blood flow imaging (CBF). During the operation they were monitored under subdural
      strip electrode ECoG for the localization of corticoepileptogenic focus. The
      results showed that the sensitivity rate of localization with SPECT for
      corticoepileptogenic focus location was 97.87%.

PMID- 7807608
TI  - Effects of zaizhang-I, a traditional Chinese medicine, on immunologically
      mediated aplastic anemia in mice.
AB  - Immunologically mediated aplastic anemia in mice were used as animal models to
      study the the curative effect of Zaizhang-I in term of the changes of two
      pathogenetic aspects in aplastic mice, namely the deficiency of hematopoietic
      stem cells and the disturbance of immunology. Our results demonstrated that in
      aplastic mice, after treatment by Zaizhang-I, the loss of mature hematopoietic
      cells (WBC, RBC, Plt) were reduced, and marrow cellular cytosis, and their
      clinical findings were improved, indicating a partial remission. The present data
      show that its curative mechanism lies in the action of promoting the recovery of
      colony forming unit-spleen (CFU-S) and reversing immunologically-induced plasma
      colony forming unit granulocyte/macrophage (CFU-GM) inhibitory activity. Natural
      killer cells activity (Nka) and interleukin-2, tumor necrosis factors (TNF) were
      also so examined to further understand the mechanism by which Zaizhang-I reverse
      plasma hematopoietic activity.

PMID- 7807609
TI  - Anthelmintic effect of levamisole against Angiostrongylus cantonensis in mice.
AB  - Levamisole, in dosages of 2.5, 5, 10, and 25 mg/kg/day, was given orally by
      orogastric tube beginning 5, 10, 15, and 20 days after the infection of ICR mice
      with 50 third-stage larvae of Angiostrongylus cantonensis. Medication was given
      for 7, 14 or 21 consecutive days. The mice in each group were sacrificed 3 days
      after cessation of treatment and the brains were examined for parasites. Complete
      anthelmintic effects could be obtained when treatment was started 10 days post
      infection with dosages as low as 2.5 mg/kg/day for 21 consecutive days. Over 90%
      worm reduction was achieved in the two-week treatment group with medication
      beginning 5 days after infection at diverse dosages. High dose were given in the
      treatment groups beginning 15 days post-infection. When the commencement of
      medication was delayed to 20 days post-infection, worm reduction rates were
      around 50% in spite of long periods and/or high dosages of medication.

PMID- 7807610
TI  - Treatment of femoral fracture with nonunion.
AB  - Thirty-four patients with femoral nonunion were managed by autogenous and/or
      allogenous bone graft alone, or internal fixation (including DCP or
      intramedullary nail) combined with bone graft, or external fixation in Taichung
      Veterans General hospital. Adequate follow-up study was obtained in 32 patients;
      two patients were unable to be contacted for follow-up. All 32 patients had
      received one or more operations. All but four patients showed clinical and
      radiological union, with an overall union rate 87.5%. Twenty-five patients
      (89.3%) returned to work, but half of these patients changed jobs. All twenty
      eight patients with solid unions could walk, but eleven patients (39.3%) had a
      slight limp. Twenty-two patients (78.6%) could squat, and all patients could
      straighten their knees. Fourteen patients (50%) complained of occasional soreness
      over the operated area. In our limited experience, most femoral nonunions result
      from (1) inappropriate selection and usage of internal fixator, (2) severe
      stripping of soft tissue around the fracture site, or inappropriate usage of
      cerclage wire, and (3) infection. Treatment must depend on the causes and types
      of nonunion. In this study, a high union rate and good functional recovery were
      achieved with interlocking nails with or without autogenous bone graft. Plating
      would extend the time for union to take place, and even resulted in refracture of
      the plate by contact with the medial cortex when there was no medial buttress. In
      general, detailed planning before operation, skilled surgical techniques and
      aseptic procedures are essential in the prevention and treatment of nonunion.

PMID- 7807611
TI  - Localization of fmrfamide-like immunoreactivity in the peripheral organs and its
      cross reaction with neuropeptide Y in the rat.
AB  - The molluscan cardioexcitatory peptide (FMRFamide) is a tetrapeptide.
      Neuropeptide Y (NPY) is a 36 amino acid peptide. Functionally, NPY is classified
      as a co-transmitter in the vasculatures of many organs and shows potent
      vasoconstriction. Coexistence of FMRFamide with NPY has been demonstrated in the
      central nervous system. The localization and distribution of NPY in the
      peripheral organs have been demonstrated mainly by radioimmunoassay. The
      localization and distribution, however, have not been investigated by
      immunohistochemistry. Therefore we present and compare the distribution of NPY-
      and FMRFamide-like immunoactivities in several peripheral organs of rats.
      Analysis of these data will reflect whether there is a cross reaction of
      FMRFamide with NPY antiserum or not. We have demonstrated both NPY- and FMRFamide
      like nerve fibers in the vasculatures of the kidney, liver, pancreas, spleen,
      submandibular gland, lung and small intestine. The distribution pattern of these
      immuno-reactivities of the peripheral organs showed some extent of similarity.
      Radioimmunoassay indicated that FMRFamide possessed the ability to react with NPY
      antiserum. This study demonstrated that the presence of FMRFamide immuno
      reactivity in rat peripheral organs represents cross-reactivity of NPY with the
      FMRFamide anti serum. Such a result can be explained if antisera against NPY and
      FMRFamide recognize the carboxy-terminal sequence of -Arg-X-amide in the
      respective peptides.

PMID- 7807612
TI  - Hypersensitivity pneumonitis: bagassosis.
AB  - Pneumoconiosis from inorganic dusts is very common worldwide and has been studied
      by many experts in Taiwan. However, pneumoconiosis due to organic dusts, i.e.
      hypersensitivity pneumonitis, seems rather uncommon in Taiwan, and to our best
      knowledge there has been no related report so far. In this study, we shall report
      five cases of bagassosis. These five patients all were men, ranging in age from
      29 to 52 years. One of them worked at a sugarcane factory, and the remaining four
      all worked at the paper mills. The exposure history to organic dusts ranged from
      2 days to 15 years. Their chief complaints were cough, dyspnea, and fever. The
      chest roentgenographic manifestations in our patients could mainly be subdivided
      into three patterns; i.e. reticulonodular infiltrates (three cases), reticular
      infiltrates (one case), and miliary nodular infiltrates (one case). These lesions
      were located diffusely with predilection for both lower lung fields. Three
      patients received bronchoalveolar lavage (BAL), which revealed a predominantly
      lymphocytic population. Arterial blood gas determinations in room air showed
      hypoxemia in most of them, but none of them were hypercapnic. Pulmonary function
      testing typically showed a restrictive ventilatory pattern in all of our cases,
      and the most sensitive diffusion capacity of carbon monoxide (DLco) ranged from
      43% to 78% of the normal value. All of our patients received corticosteroid
      therapy after establishment of the diagnosis and had rather satisfactory
      responses. In addition, we also present possible preventive measures in the field
      of industrial hygiene.

PMID- 7807613
TI  - [Dose measurement and risk evaluation in intraoral periapical radiography].
AB  - To measure the absorbed dose and evaluate the radiation risk of patient from full
      mouth series intraoral dental radiography, we used the LiF thermoluminescent
      dosimeters (TLD-100 chips) to detect the radiation dose of patients and RT
      HUMANOID phantom as well. We also used water phantom and extracted human teeth to
      simulate the oral cavity and measure the absorbed dose of tooth while the
      intraoral dental radiography was taken. The average absorbed dose of skin near
      the thyroid gland of patient is 72.2 mu Gy from full mouth series intraoral
      radiograph with 14 dental films (speed D) using Gendex Panelipse II X-ray machine
      (75-80kVp, 15mA, 0.25s, FSD = 34-36 cm) with neck shield protection, and the
      radiation risk of thyroid gland of stochastic effect is estimated to be 3.6 x 10(
      8). We also calculated the effective atomic number of enamel and dentin for
      obtaining the conversion factor of tooth. Four sets of figures were drawn to
      express the absorbed dose in water phantom and tooth in some different exposure
      conditions.

PMID- 7807614
TI  - [How should high concentration oxygen be provided with a resuscitator during
      resuscitation?].
AB  - Oxygen is essential to life. When one is suffering from illness or trauma, the
      oxygen demand increases because of catabolic response. High concentration oxygen
      is therefore required in resuscitation. In Taiwan, as well as in other countries,
      medical personnel usually provide artificial ventilation with a resuscitator.
      However, the percentage of oxygen delivered from the bag varies significantly in
      different conditions. To provide high-concentration oxygen during resuscitation,
      it is necessary to use a resuscitator with an oxygen reservoir and sufficient
      supplemental oxygen flow.

PMID- 7807615
TI  - [The utilization of health care by the elderly with chronic health problems in
      Kaohsiung City].
AB  - The purpose of this study was (1) to ascertain whether or not the elderly
      utilized the health care system and did follow-up after the initial free health
      check-up and screening; (2) to investigate the types of chronic health problems
      the elderly who utilize health care had and their reasons for using the health
      care system; and (3) to explore related factors that influence the utilization of
      health care by the elderly. In this study, 484 elderly individuals were
      interviewed by home visits. All names were from the 11 public health clinics in
      Kaohsiung City, and all subjects had been diagnosed with one of the following
      disorders: heart disease, diabetes mellitus, hypertension, liver and biliary
      disorder, urinary disorder, or lung disease. Data were statistically analyzed by
      means of descriptive and analytical methods, %, t-test, Chi-Square test and odds
      ratio. The major findings of this study were as follows: (1) the utilization rate
      by chronically ill elderly was 80.2%. (2) elderly with multiple utilization of
      the health care system comprised 33.8%. (3) the variables influencing the
      utilization of the health care system included: perceived susceptibility, fixed
      physician, medical insurance, doctor's attitude, social support, community health
      nurse follow-up, the number of diseases, perceived severity of the illness, and
      attitude of health.

PMID- 7807616
TI  - Surgical correction of sinus venosus atrial septal defect associated with partial
      anomalous pulmonary venous connection to high superior vena cava--case report.
AB  - A 63-year-old woman complained of general malaise and insomnia initially. Atrial
      septal defect was diagnosed by transthoracic echocardiography thereafter. She had
      not received complete cardiac studies until progressive dyspnea was noted half a
      year later. After a series of examinations, sinus venosus type atrial septal
      defect (ASD) associated with partial anomalous pulmonary venous connection to
      high superior vena cava (SVC) and persistent left SVC was documented. Surgical
      correction was performed later. The postoperative course was smooth and her
      condition improved gradually at 10-month follow-up.

PMID- 7807617
TI  - Haemophilus influenzae b vaccines.

PMID- 7807618
TI  - Has primary health care reduced infant mortality in east Bhutan? The effects of
      primary health care and birth spacing on infant and child mortality patterns in
      east Bhutan.
AB  - In a traditional, agricultural society in East Bhutan studies of infant and child
      mortality were carried out in 1984 and 1991. Mothers were interviewed regarding
      births during the preceding 5 years and deaths among these children. A
      significant fall in infant mortality rate (IMR) from 145 to 49 (P < 0.001) was
      found. In 1991, measles was almost eliminated as a cause of death. Families with
      1, 2 and 3 children, respectively, during the period studied, were found to have
      significantly different IMRs, with higher mortality for higher number of births
      (P < 0.001 for 1984 and P = 0.002 for 1991). To quantify the effect on mortality
      from birth intervals both the possibility of reverse causation and confounding
      factors, such as socio-economic conditions must be considered, but the study
      suggests that the association is partly causal. The living conditions of the
      population do not seem to have improved so greatly as to have caused the
      reduction in IMR. Monthly Mother and Child Health outreach clinics and a network
      of Village Health Workers have provided the framework necessary for
      implementation of different health programmes. As a result Primary Health Care
      has improved during the period between 1984 and 1991, and may have contributed
      considerably to the reduced mortality.

PMID- 7807619
TI  - Diabetes mellitus in children suffering from beta-thalassaemia.
AB  - Insulin-dependent diabetes mellitus (IDDM) is a frequent complication in patients
      with beta-thalassaemia major. It is believed to be a consequence of the damage
      inflicted by iron overload to the pancreatic beta-cell. Liver disorders and
      genetic influences seem to be additional predisposing factors to diabetes
      mellitus in patients with beta-thalassaemia. Ethnic variations are frequently
      reported on prevalence and complications of diabetes mellitus in the beta
      thalassaemia patients. We investigated 50 Saudi children (< 15 years) with beta
      thalassaemia major and 50 beta-thalassaemia minor, and age- and sex-matched
      controls for the prevalence of diabetes mellitus, and its relation to hitherto
      claimed predisposing factors. Fasting blood glucose, plasma insulin level, liver
      function tests, plasma ferritin, iron, and transferrin were assessed in each
      patient and glucose tolerance was evaluated. Results in patients with beta
      thalassaemia major were compared with those obtained for beta-thalassaemia minor
      and the controls. The results showed moderate elevation of ferritin level in the
      majority of the beta-thalassaemia major despite desferroxamine therapy. Either
      hyperinsulinaemia or hypoinsulinaemia was encountered in the majority of these
      patients. The prevalence of diabetes mellitus was 6 per cent compared to 2 per
      cent in the beta-thalassaemia minor and normal children. Impaired glucose
      tolerance (IGT) occurred at a significantly higher (24 per cent) frequency in the
      beta-thalassaemia major compared to 2 and 0 per cent in the beta-thalassaemia
      minor patients and normal controls, respectively. The prevalence of diabetes
      mellitus was significantly lower in the Saudi thalassaemic patients compared to
      the results obtained from patients of other ethnic groups reported in
      literature.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7807620
TI  - Breastfeeding and weaning practices in Saudi Arabia.
AB  - A National Child Health Survey was conducted during 1987 for which a stratified
      multi-stage sampling was done. Out of the 8482 mothers interviewed 6131 had at
      least one live birth 5 years or less before the survey. Eighty-two per cent of
      the currently breastfed children, were less than 6 months of age, but only 55 per
      cent of the infants up to 1 month of age were breastfed without supplementation.
      The mean interval between supplementation and weaning for all age groups of
      mothers was 7.7 months. The predominant causes of weaning were child reaching
      suitable age and mother not having enough milk. This study establishes base line
      information about feeding practice on a nationwide basis in Saudi Arabia.

PMID- 7807621
TI  - Diarrhoeal disease, oral rehydration, and childhood mortality in rural Egypt.
AB  - The Egyptian National Control of Diarrhoeal Diseases Project (NCDDP) is reported
      to have had great success in improving case management of diarrhoea, and in
      reducing diarrhoea-related mortality among children, while deaths due to other
      causes have remained unchanged. Recent reports have claimed that with this
      dramatic decline in diarrhoea mortality, respiratory infection is now the main
      cause of child death in Egypt. As a result, the degree of commitment to control
      of diarrhoeal disease activities has been greatly reduced. We present new data
      from a large prospective study that confirms much of the success of the NCDDP,
      but which questions the extent of the claimed project impact on mortality. Child
      mortality has declined greatly over the past decade. However, deaths from other
      causes have declined almost as much as those from diarrhoea, and most
      importantly, diarrhoea remains the main cause of death among children. Our
      discussion demonstrates the need for appropriate methodology in evaluating the
      mortality impact of an intervention, and to the very great importance of
      reinvigorating control of diarrhoeal diseases activities in Egypt.

PMID- 7807622
TI  - Acute respiratory infections in Nigerian children: prospective cohort study of
      incidence and case management.
AB  - A community-based prospective surveillance and case management study of acute
      respiratory infection (ARI) in children aged 2-60 months of age was carried out
      over a 12-month period in Pakata, a semi-urban community in Ilorin, Kwara State,
      Nigeria. A cohort of 481 children was followed by trained community health
      assistants with thrice weekly home visits to record all symptoms and signs of
      ARI, and institute treatment based on WHO recommendations. There were three
      episodes of mild, moderate, or severe ARI per child per year, including 1.3
      pneumonia episodes per child per year. The peak of infection corresponded to the
      rainy season (July-November), and a smaller peak to the dry season (February
      April). Most of the health worker decisions were considered appropriate, although
      there was a tendency toward over-treatment with antibiotic drugs. An effective
      referral system was established from the community to a tertiary centre. There
      were no ARI-related deaths during the study period. These data indicate that a
      system of case management using trained community health workers can improve case
      management of ARI and may prevent severe ARI-related disease and deaths.

PMID- 7807623
TI  - Risk factors for small for gestational age births in Ahmedabad, India.
AB  - Intra-uterine growth retardation is an important public health problem in many
      developing countries. The authors conducted a case-control study of low birth
      weight (LBW) in three teaching hospitals and a population survey in Ahmedabad
      city, India during 1987-1988. To identify and quantify risk factors for small for
      gestational age births, we divided the low birth weight and control infants into
      small for gestational age (SGA, n = 617) and appropriate for gestational age
      (AGA, n = 1851) using an Indian birth weight by gestational age standard.
      Logistic regression was used to estimate adjusted odds ratios for important risk
      factors. Prevalence of risk factors was estimated from a community sample survey
      of mothers (n = 1102) who had delivered in the past year. Attributable risks were
      calculated from odds ratios and prevalence data. The most important risk factors
      for SGA was poor maternal nutritional status (weight < 51 kg) with an
      attributable risk of 42 per cent. Other significant risk factors were anaemia,
      primiparity, poor obstetric history, lack of antenatal care and hypertension
      during pregnancy, and birth defects, each of which contributed only moderately to
      the attributable risk. The analysis indicates that improvement of maternal
      nutrition and antenatal care might prevent a substantial portion of SGA births in
      this and similar populations.

PMID- 7807625
TI  - Can women's organizations bring about health development?

PMID- 7807624
TI  - Antibody response to measles immunization in rural Ghanaian infants.
AB  - We investigated optimal age of measles immunization in infants aged 3-11 months
      in rural villages of Ghana, and determined seroconversion rate in the same infant
      population following further attenuated measles vaccination with Schwarz vaccine.
      The prevalence of passively acquired antibody was 11 per cent in infants younger
      than 6 months, 10 per cent in infants 6 months old, and 3 per cent in infants 7
      months old or older. Seroconversion rates in each age group were less than 50,
      87, and 92 per cent, respectively. We then immunized 47 7-month-old infants. The
      seroconversion rate was 92 per cent in this group. There were no clinical adverse
      effects due to the vaccination. We conclude that measles vaccination could be
      administered effectively at the age of 7 months with an excellent seroconversion
      rate.

PMID- 7807626
TI  - Dehydration in Kwashiorkor cases: a bad prognosis factor in Senegal.

PMID- 7807627
TI  - Trial of co-trimoxazole versus procaine penicillin G and benzathin penicillin +
      procaine penicillin G in the treatment of childhood pneumonia.
AB  - This study, which aimed to assess the results of three different regimens in the
      treatment of pneumonia, was carried out at the Pediatric Outpatient Department of
      Capa Children's Hospital in Istanbul on 151 patients aged between 4 months and 14
      years. The first group (n = 46) received co-trimoxazole orally for 10 days and
      the second group (n = 63) procaine penicillin G in intramuscularly for 10 days.
      Benzathin penicillin G combined with procaine penicillin G was given to the third
      group (n = 42) as a single dose intramuscularly. While the best results were
      obtained with penicillin procaine G, no statistically significant difference was
      found between this regimen and co-trimoxazole therapy (chi 2 = 0.305023 P = 0.5).
      We suggest that co-trimoxazole is easy to administer and cost effective in the
      ambulatory treatment of pneumonia in children.

PMID- 7807628
TI  - Vitamin A supplementation in post-measles complications.
AB  - One-hundred-and-seventy-seven children with post-measles complications divided
      into two comparable groups were studied for the effect of Vit.A Supplementation.
      Eighty-nine children received Vit.A in doses of 200,000 units daily on two
      consecutive days in addition to antibacterials and other supportive care and 88
      did not reveice Vit.A. The case fatality rate was 16 per cent in those who
      received VIT.A, while the same was 32 per cent in those who did not receive Vit.A
      (P < 0.02). There was no statistical difference in the mortality rate among two
      groups when the children were suffering from severe malnutrition or
      encephalopathy (P > 0.1).

PMID- 7807629
TI  - Determinants of nutrition status among children in the eastern region of Ghana.
AB  - A cross-sectional survey of children's weights was included in a population study
      which was designed to identify and measure the determinants of immunization
      status of 12-18-month-old children of 294 mothers in the Eastern Region of Ghana.
      Birth weight, among a subgroup of 91 children where this information was
      available from the mothers' Road To Health cards, was the variable with which
      current weight-for-age Z scores was most strongly associated (r = 0.38).
      Associations of current weight-for-age with certain socio-economic variables, at
      or close to statistically significant levels, corresponded with similar or
      stronger associations of birth weight with these same socio-economic variables.
      Cross-sectional studies of young children, to identify associations and possible
      determinants of nutrition status, are more informative where there is a high Road
      To Health card coverage and where birth weights have been recorded on these
      cards.

PMID- 7807630
TI  - Comparative usefulness of arm, thigh and calf circumference for screening low
      birth weight infants.

PMID- 7807632
TI  - Persistent diarrhoea: an unusual presentation of typhoid fever.

PMID- 7807631
TI  - Risk factors in protein-energy malnutrition among infants and toddlers.

PMID- 7807633
TI  - The changing pattern of causative bacterial agents in childhood meningitis.

PMID- 7807634
TI  - Auditory temporal resolution in multiple sclerosis.
AB  - Disturbances of hearing in multiple sclerosis patients have been variably
      reported, likely because standard audiologic testing emphasizes assessment of
      peripheral, rather than central, auditory function. This study investigated a
      group of patients with multiple sclerosis (MS), prospectively selected on the
      basis of magnetic resonance imaging (MRI) scans. Five of these patients had
      demyelinating lesions that included the rostral auditory fibre tracts, while
      another seven patients had lesions restricted to brainstem auditory sites. A
      further four had no lesions in the distribution of their auditory pathways. A
      comprehensive battery of audiometric tests, including standard audiometry and
      retrocochlear testing, was performed. In addition, their findings on
      electrophysiologic testing, including auditory brainstem responses (ABR) and
      middle latency responses (MLR), were studied. Finally, their performances in gap
      detection and speech recognition in continuous and interrupted background noise
      were examined to assess their auditory temporal resolution. The MS patients were
      found to be selectively impaired under the interrupted masker of this speech-in
      noise paradigm, confirming a temporal processing defect. Furthermore, these
      patients' performances suggested a predominant role of forebrain pathways in
      mediating auditory temporal resolution.

PMID- 7807635
TI  - Laser-assisted serial tonsillectomy.
AB  - Laser ablation of the palatine tonsils is a useful alternative to tonsillectomy
      in adults. Cryptic tonsillitis is a common problem causing recurrent infection,
      sore throat, and halitosis. Elimination and/or obliteration of surface pockets
      (crypts) of the palatine tonsils utilizing the CO2 laser was effective in 86
      patients treated in the past 4 years. Ablation of the tonsil surface was
      performed in stages under local anesthesia in an office setting; CO2 laser energy
      delivered through the "SwiftLase" handpiece extension provided char-free,
      superficial layer ablation of tissue. "SwiftLase" is easily installed onto
      existing CO2 laser units and provides high-power densities by utilizing a focused
      laser beam in an extremely fast uniform scan over an extended area (up to 4 mm)
      within a fraction of a second. This method and results of its use are discussed.

PMID- 7807636
TI  - Laser-assisted uvula-palatoplasty for snoring.
AB  - Laser-assisted uvula-palatoplasty (LAUP) is a new and effective surgical method
      for the elimination of habitual snoring. LAUP is safely performed under local
      anesthesia in the office, and it provides progressive enlargement of the
      oropharyngeal air space by reshaping and restructuring the uvula, soft palate,
      and pharyngeal pillars utilizing the CO2 laser with special attachments. LAUP can
      also reduce oropharyngeal obstruction that may occur during sleep in patients
      with obstructive sleep apnea syndrome. Our experience includes over 335 patients
      evaluated and treated within the past year. Successive laser ablation of the
      vibrating structures, such as the uvula, soft palate, and posterior pharyngeal
      pillars, provided an 84% cure rate. In addition, 7% of the patients reported
      significant improvement in the loudness of their snore. The major advantage of
      this surgical technique is that it is a safe, simple, reliable, and bloodless
      procedure that can be performed in the office. This method and the results of its
      use are discussed.

PMID- 7807637
TI  - Soft tissue rhinoplasty.
AB  - The majority of rhinoplasty studies emphasize the management of the cartilaginous
      and bony nasal framework. Often overlooked is the soft tissue envelope. One
      hundred consecutive rhinoplasty patients were studied with respect to their soft
      tissue deformities, the surgical techniques applied for correction, and the
      aesthetic outcome. Results were analyzed utilizing preoperative and postoperative
      assessment sheets, progress notes, and photographs. The importance of proper
      diagnosis and management of soft tissue deformities in achieving superior
      aesthetic results is discussed. As well, clinical examples of illustrative
      deformities and their corrections are presented.

PMID- 7807638
TI  - Search for the human papillomavirus in nasal polyps, using a polymerase chain
      reaction-method.
AB  - Viral etiology of nasal polyps was postulated as many as 40 years ago, but so
      far, no study has shown an association or causal relation between any specific
      virus and nasal polyps. By using the polymerase chain reaction (PCR) technique,
      nasal polyps from both 10 patients with intolerance to nonsteroidal anti
      inflammatory drugs (NSAID intolerance) (e.g., Aspirin) and from 10 patients with
      no history of NSAID intolerance were studied for the presence of papillomavirus
      DNA. Nasal mucosa from 10 patients who had undergone surgery for septoplasty
      served as controls. The PCR test used covers approximately 30 different types of
      human papillomaviruses. In this test, all tissue samples studied were found
      negative for papillomavirus DNA.

PMID- 7807639
TI  - Dermabrasion: clinical uses in otolaryngology.
AB  - Dermabrasion has been a mainstay for the treatment of significant acne scarring.
      Recently, however, there has been a trend toward expanding the use of
      dermabrasion to include many other reconstructive procedures. Dermabrasion has
      become a valuable tool for the facial plastic and reconstructive surgeon. This
      article presents a thorough review of the expanded indications for dermabrasion
      in the head and neck region. In addition, the contraindictions, anatomic
      considerations, equipment, technique, postoperative course, and potential
      complications of facial dermabrasion are discussed.

PMID- 7807640
TI  - Computer-assisted surgical techniques: a vision for the future of otolaryngology
      head and neck surgery.
AB  - Our specialty relies increasingly on technologic advancements and increased
      knowledge of pathophysiology at the cellular and molecular level; these trends
      will continue. The consequences in the laryngologic, otologic, and rhinologic
      surgery are presented. Envision the surgeon positioned at a computer workstation
      to perform surgery. Following endoscopy and the placement of the
      microlaryngoscope, the only contact he or she will have with the patient is
      through robotic "hands" on the end of thin rods. These hands thread through the
      laryngoscope and hold tissue without any tremor. Multiple-wavelength lasers are
      available, each tuned to optimally incise particular tissue types. The laser beam
      will be delivered under computer control with active feed-back systems involving
      ultrasonic imaging, infrared thermography, and photoacoustic monitoring. Similar
      visions are presented in otology and rhinology with microinstrumentation and
      virtual reality.

PMID- 7807641
TI  - Accuracy of fine needle aspiration in the pre-operative diagnosis of thyroid
      neoplasia.
AB  - The aim of this study was to determine the accuracy and clinical utility of fine
      needle aspiration (FNA) for the preoperative diagnosis of patients presenting
      with solitary thyroid nodules. Between 1987 and 1991, 317 patients with a thyroid
      nodule underwent FNA. Surgery was performed on 98 of the patients, and the
      cytologic findings were correlated with the final histologic diagnoses for these
      cases. Of the 98 patients operated on, satisfactory aspirates were obtained in 85
      patients and classified as either malignant, suspicious for malignancy, or
      benign. The FNA was correct in predicting malignancy in 29 of 35 nodules (82.9%).
      With the benign nodules, FNA was correct in 44 of 50 nodules (88%). The overall
      accuracy of FNA was 85.9%. The accuracy for the combination of FNA and frozen
      section (FS) was 92.6%. We conclude that both FNA and FS are accurate tests that
      play a useful role in the pre- and intraoperative diagnostic evaluation of
      patients presenting with solitary thyroid nodules.

PMID- 7807642
TI  - Efficacy of primary tracheoesophageal puncture in laryngectomy rehabilitation.
AB  - Primary voice restoration has been the preferred treatment for laryngectomy
      patients at the Sir Mortimer B. Davis Jewish General Hospital since 1986. This
      study reviews 71 consecutive patients over a 5-year period. Number, types of
      complications, and whether post-surgery radiation increases complications were
      studied. The Robillard Shultz-Harrison Tracheoesophageal Puncture Rating Scale,
      measuring use, voice quality, and independence at 1, 3, 6, and 12 months, was
      employed to rate functional outcome. A Patient Satisfaction Questionnaire was
      used to assess patient satisfaction. The patients were subdivided into two
      groups. Group A, 24 patients with no radiation post-surgery, was compared to
      Group B consisting of 22 patients, all of whom received postsurgical radiation
      treatment. There was no significant difference between groups in the number and
      types of complications. The most frequent problems for both groups were immediate
      and delayed extrusion, tracheoesophageal fistula migration, and pharyngocutaneous
      fistula. Group A achieved better functional communication scores statistically
      significant only at the 3-month interval (p = .02). Cumulative scores from the
      Patient Satisfaction Questionnaire revealed that 60% of the patients were
      moderately to very satisfied with tracheoesophageal speech. Modification in
      rehabilitation protocol to reduce complications and a significantly shortened
      list of contraindications for primary TEP are presented.

PMID- 7807643
TI  - Using the nicotine patch to stop smoking.

PMID- 7807644
TI  - Using the nicotine patch to stop smoking.

PMID- 7807645
TI  - World War II's most highly decorated US physician.

PMID- 7807646
TI  - Understanding MeSH for literature searches.

PMID- 7807647
TI  - Understanding MeSH for literature searches.

PMID- 7807648
TI  - Lower limb amputation and the diabetic foot.

PMID- 7807649
TI  - Screening for scoliosis.

PMID- 7807650
TI  - African refugee disasters increase the risk of blindness.

PMID- 7807651
TI  - States face rocky road to reform.

PMID- 7807652
TI  - Effective response to emerging diseases called an essential priority worldwide.

PMID- 7807653
TI  - From the Institute of Medicine.

PMID- 7807654
TI  - From the Centers for Disease Control and Prevention. Detection of notifiable
      diseases through surveillance for imported plague--New York, September-October
      1994.

PMID- 7807655
TI  - From the Centers for Disease Control and Prevention. National notifiable diseases
      reporting--United States, 1994.

PMID- 7807656
TI  - From the Centers for Disease Control and Prevention. Bolivian hemorrhagic fever-
      El Beni Department, Bolivia, 1994.

PMID- 7807657
TI  - From the Centers for Disease Control and Prevention. Progress toward the global
      elimination of neonatal tetanus, 1989-1993.

PMID- 7807658
TI  - Effects of estrogen or estrogen/progestin regimens on heart disease risk factors
      in postmenopausal women. The Postmenopausal Estrogen/Progestin Interventions
      (PEPI) Trial. The Writing Group for the PEPI Trial.
AB  - OBJECTIVE: To assess pairwise differences between placebo, unopposed estrogen,
      and each of three estrogen/progestin regimens on selected heart disease risk
      factors in healthy postmenopausal women. DESIGN: A 3-year, multicenter,
      randomized, double-blind, placebo-controlled trial. PARTICIPANTS: A total of 875
      healthy postmenopausal women aged 45 to 64 years who had no known
      contraindication to hormone therapy. INTERVENTION: Participants were randomly
      assigned in equal numbers to the following groups: (1) placebo; (2) conjugated
      equine estrogen (CEE), 0.625 mg/d; (3) CEE, 0.625 mg/d plus cyclic
      medroxyprogesterone acetate (MPA), 10 mg/d for 12 d/mo; (4) CEE, 0.625 mg/d plus
      consecutive MPA, 2.5 mg/d; or (5) CEE, 0.625 mg/d plus cyclic micronized
      progesterone (MP), 200 mg/d for 12 d/mo. PRIMARY ENDPOINTS: Four endpoints were
      chosen to represent four biological systems related to the risk of cardiovascular
      disease: (1) high-density lipoprotein cholesterol (HDL-C), (2) systolic blood
      pressure, (3) serum insulin, and (4) fibrinogen. ANALYSIS: Analyses presented are
      by intention to treat. P values for primary endpoints are adjusted for multiple
      comparisons; 95% confidence intervals around estimated effects were calculated
      without this adjustment. RESULTS: Mean changes in HDL-C segregated treatment
      regimens into three statistically distinct groups: (1) placebo (decrease of 0.03
      mmol/L [1.2 mg/dL]); (2) MPA regimens (increases of 0.03 to 0.04 mmol/L [1.2 to
      1.6 mg/dL]); and (3) CEE with cyclic MP (increase of 0.11 mmol/L [4.1 mg/dL]) and
      CEE alone (increase of 0.14 mmol/L [5.6 mg/dL]). Active treatments decreased mean
      low-density lipoprotein cholesterol (0.37 to 0.46 mmol/L [14.5 to 17.7 mg/dL])
      and increased mean triglyceride (0.13 to 0.15 mmol/L [11.4 to 13.7 mg/dL])
      compared with placebo. Placebo was associated with a significantly greater
      increase in mean fibrinogen than any active treatment (0.10 g/L compared with 
      0.02 to 0.06 g/L); differences among active treatments were not significant.
      Systolic blood pressure increased and postchallenge insulin levels decreased
      during the trial, but neither varied significantly by treatment assignment.
      Compared with other active treatments, unopposed estrogen was associated with a
      significantly increased risk of adenomatous or atypical hyperplasia (34% vs 1%)
      and of hysterectomy (6% vs 1%). No other adverse effect differed by treatment
      assignment or hysterectomy status. CONCLUSIONS: Estrogen alone or in combination
      with a progestin improves lipoproteins and lowers fibrinogen levels without
      detectable effects on postchallenge insulin or blood pressure. Unopposed estrogen
      is the optimal regimen for elevation of HDL-C, but the high rate of endometrial
      hyperplasia restricts use to women without a uterus. In women with a uterus, CEE
      with cyclic MP has the most favorable effect on HDL-C and no excess risk of
      endometrial hyperplasia.

PMID- 7807659
TI  - The decline in coronary artery bypass graft surgery mortality in New York State.
      The role of surgeon volume.
AB  - OBJECTIVE: To examine the longitudinal relationship between surgeon volume and in
      hospital mortality for coronary artery bypass graft (CABG) surgery in New York
      State and to explain changes in mortality that occurred over time. DESIGN:
      Observation of clinically risk-adjusted operative mortality over time. SETTING:
      All 30 New York State hospitals in which CABG surgery was performed for 1989
      through 1992. PATIENTS: All 57,187 patients undergoing isolated CABG surgery in
      New York State in 1989 through 1992 in the 30 hospitals. MAIN OUTCOME MEASURES:
      Actual, expected, and risk-adjusted mortality. RESULTS: Risk-adjusted in-hospital
      mortality decreased for all categories of surgeons. Low-volume surgeons (< or =
      50 operations per year) experienced a 60% reduction in risk-adjusted mortality in
      the 4-year period, whereas the highest-volume surgeons (> 150 operations per
      year) experienced a 34% reduction. The percentage of patients undergoing CABG
      surgery by low-volume surgeons decreased from 7.6% in 1989 to 5.7% in 1992, a 25%
      decrease. CONCLUSIONS: The overall decline in risk-adjusted mortality could not
      be explained by shifts in patients away from low-volume surgeons to high-volume
      surgeons. The proportionately larger decrease in risk-adjusted mortality for low
      volume surgeons could not be explained by changes in patient case mix or by
      improvements in the performance of surgeons with persistently low volumes. Part
      of the decrease was a result of the exodus of low-volume surgeons with high risk
      adjusted mortality (in all years studied), the markedly better performance of
      surgeons who were new to the system (especially in 1991 and 1992), and the
      performance of surgeons who were not consistently low-volume surgeons (especially
      in 1992).

PMID- 7807660
TI  - Trends in antimicrobial drug prescribing among office-based physicians in the
      United States.
AB  - OBJECTIVE: To assess changes in oral antimicrobial drug prescribing by office
      based physicians from 1980 through 1992, with emphasis on the treatment of otitis
      media and sinusitis and on the possible impact of demographic variables on such
      use. DESIGN: The National Ambulatory Medical Care Survey is a sample survey of
      office-based physicians in the United States conducted by the National Center for
      Health Statistics, Centers for Disease Control and Prevention. SETTING:
      Physicians' offices. PATIENTS OR OTHER PARTICIPANTS: Physicians sampled for the
      1980, 1985, 1989, and 1992 National Ambulatory Medical Care Surveys, which
      included groups of 2959, 5032, 2540, and 3000 physicians, respectively. Sample
      physicians responding in 1980, 1985, 1989, and 1992 reported data for 46,081,
      71,594, 38,384, and 34,606 sample office visits, respectively, including
      information on antimicrobial drug prescribing. MAIN OUTCOME MEASURE: Trends in
      the antimicrobial drug prescription rates. RESULTS: From 1980 through 1992,
      increasing prescribing measured by the annual drug prescription rate per 1000
      population, was found for the more expensive, broad-spectrum antimicrobial drugs,
      such as the cephalosporins; decreasing rates were observed for less expensive
      antimicrobial drugs with a narrower spectrum, such as the penicillins. No trend
      was found for trimethoprim-sulfamethoxazole, the erythromycins, or the
      tetracyclines. During the decade, an increasing trend in the visit rate to office
      based physicians for otitis media was observed, while the visit rate for
      sinusitis among adults was found to be higher in 1992 than in each of the other
      study years. CONCLUSIONS: The increased use of broader-spectrum and more
      expensive antimicrobial drugs have implications for all patients because of the
      impact on health care costs and the potential for the emergence of antimicrobial
      resistance. The data suggest that the incidence of otitis media and sinusitis is
      increasing.

PMID- 7807661
TI  - Global epidemiology of tuberculosis. Morbidity and mortality of a worldwide
      epidemic.
AB  - This article describes the global epidemiology of tuberculosis and reviews recent
      estimates of tuberculosis incidence and mortality in the world. The highest
      prevalence of tuberculosis infection and estimated annual risk of tuberculosis
      infection are in sub-Saharan Africa and Southeast Asia. Overall, almost 3.8
      million cases of tuberculosis were reported in the world in 1990, of which 49%
      were in Southeast Asia. From the period 1984 through 1986 to the period 1989
      through 1991, notification rates increased in all World Health Organization
      regions, except the American and the European regions. In 1990, there were an
      estimated 7.5 million cases of tuberculosis and 2.5 million deaths worldwide. The
      human immunodeficiency virus epidemic is causing increases in the number of
      tuberculosis cases, particularly in Africa, although increases are also expected
      in Southeast Asia. In many industrialized countries, tuberculosis has recently
      failed to decline, and in eastern Europe and the former Soviet Union, cases and
      deaths are increasing. Drug resistance is a serious problem, especially in the
      United States. If worldwide control of tuberculosis does not improve, 90 million
      new cases and 30 million deaths are expected in the decade 1990 through 1999.

PMID- 7807662
TI  - Communication with deaf patients. Knowledge, beliefs, and practices of
      physicians.
AB  - OBJECTIVE: To assess physicians' knowledge and beliefs regarding communication
      with deaf people and compare their knowledge and beliefs with their methods of
      communicating with deaf patients in their practices. DESIGN: Survey. SETTING:
      University medical center. SUBJECTS: Attending physicians in an internal medicine
      department. INTERVENTIONS: Physicians were surveyed regarding prior contacts with
      deaf patients and with deaf people outside the medical setting, and regarding
      their knowledge and beliefs concerning methods of communicating with deaf people.
      Physicians were asked to estimate the fraction of encounters in which they
      communicated with deaf patients by lipreading, writing, translation by a relative
      or friend, a sign language interpreter, or other methods. RESULTS: Writing was
      the method used most frequently in communicating with deaf patients. Although 63%
      of physicians knew that signing should be the initial method of communicating
      with deaf patients who sign, only 22% used sign language interpreters more
      frequently than other methods in their practices. Past contact with deaf people
      (P = .05), belief that communication by signing was the best means of
      communication (P = .04), and knowledge of the inefficiency of lipreading (P =
      .04) were predictors of the use of sign language interpreters for deaf patients.
      Physicians who used sign language interpreters more frequently than other methods
      believed that much more time and effort were involved in caring for deaf than for
      hearing patients compared with those who used interpreters less frequently (P =
      .08). CONCLUSION: Although most physicians believed that use of sign language
      interpreters was preferable, only a minority used them in their practices.
      Greater recognition of the advantages of signing over other methods and greater
      availability of sign language interpreters should lead to more effective
      communication between deaf patients and physicians.

PMID- 7807663
TI  - Cost and outcome of intensive care for patients with AIDS, Pneumocystis carinii
      pneumonia, and severe respiratory failure.
AB  - OBJECTIVE: To determine the costs and outcomes associated with intensive care
      unit (ICU) admission for patients with acquired immunodeficiency syndrome (AIDS)
      related Pneumocystis carinii pneumonia (PCP), and severe respiratory failure.
      DESIGN: Survival and cost-effectiveness analysis. SETTING: A large municipal
      teaching hospital serving an indigent population. PATIENTS: Consecutive patients
      intubated and mechanically ventilated for AIDS, PCP, and respiratory failure from
      1981 through 1991 (n = 113). The cohort was separated into three groups for
      analysis: patients admitted to the ICU in 1981 through 1985 (era I, n = 43),
      those admitted in 1986 through 1988 (era II, n = 33), and those admitted in 1989
      through 1991 (era III, n = 37). MAIN OUTCOME MEASURES: Hospital charges and
      survival time; cost per year of life saved, using a zero-cost, zero-life
      assumption. RESULTS: Twenty-eight (25%) of the 113 patients mechanically
      ventilated for PCP and respiratory failure survived to hospital discharge: six
      (14%) of 43 in era I, 13 (39%) of 33 in era II, and nine (24%) of 37 in era III
      (P = .04). Post-ICU admission charges averaged $57,874 for the entire cohort,
      remaining relatively stable across the three eras. Cost of care for survivors was
      significantly more expensive than for those dying before discharge. The cost of
      ICU admission and subsequent hospitalization averaged $174,781 per year of life
      saved; $305,795 in era I, $94,528 in era II, and $215,233 in era III. Improved
      survival rates and shorter lengths of ICU stay led to the improved cost
      effectiveness in era II, while the opposite trends resulted in worsening cost
      effectiveness in recent years. The strongest predictors of hospital mortality in
      era III were low CD4 cell counts on hospital admission and the development of
      pneumothorax during mechanical ventilation. CONCLUSIONS: The cost-effectiveness
      of intensive care for patients with PCP and severe respiratory failure improved
      during the first 8 years of the AIDS epidemic but fell in recent years such that
      it is now below that of many accepted medical interventions.

PMID- 7807664
TI  - New therapeutic strategies for patients with gastrointestinal malignancies using
      biochemical modulation of fluorouracil.

PMID- 7807665
TI  - PEPI in perspective. Good answers spawn pressing questions.

PMID- 7807666
TI  - Emerging and reemerging global microbial threats. Call for papers.

PMID- 7807668
TI  - What should be done now that national health system reform is dead?

PMID- 7807667
TI  - How to approach universal access to basic medical care without our government
      doing it.

PMID- 7807669
TI  - Quality of health and health care.

PMID- 7807670
TI  - Academic medicine. Facing change.

PMID- 7807671
TI  - Health system reform. Whither or whether?

PMID- 7807672
TI  - The 1995 health policy debate.

PMID- 7807673
TI  - Advancing America's health.

PMID- 7807675
TI  - The first step.

PMID- 7807674
TI  - Moving ahead with health care system reform.

PMID- 7807676
TI  - What to do now on health care system reform.

PMID- 7807677
TI  - The community. Where reform rolls on.

PMID- 7807678
TI  - Welcome to year 83.

PMID- 7807679
TI  - Left atrial backward ejection in symptomatic hypertrophic cardiomyopathy-
      assessment by transthoracic and transesophageal Doppler echocardiography.
AB  - BACKGROUND: During atrial contraction, the left atrium produces both forward
      ejection to the left ventricle and backward ejection to pulmonary veins. PURPOSE:
      To determine quantitatively left atrial ejection performance in symptomatic
      hypertrophic cardiomyopathy (HCM) patients by using left atrial systolic time
      intervals. METHOD: Thirty-one patients with symptomatic HCM and sinus rhythm and
      31 normal subjects were studied with transthoracic and transesophageal Doppler
      echocardiography. Left atrial pre-ejection period (APEP), corrected atrial pre
      ejection period (APEPc), and the duration (AET) and the time velocity integral
      (IA) of the atrial contraction wave in transmitral flow were determined. The
      duration (PV-AET) and the time velocity integral (PV-IA) of reverse pulmonary
      venous flow during atrial contraction were also determined. RESULTS: For normal
      subjects, significant correlations were found between APEP and
      electrocardiographic P wave duration (r = 0.78, p < 0.001), and between APEPc and
      left atrial forward ejection indices (AET: r = -0.42, p = 0.01, IA: r = -0.54, p
      < 0.05, respectively), but not between APEP and either of the two latter indices.
      These findings indicate that, for normal subjects, APEPc is a better index of
      left atrial systolic function than APEP. In contrast, for HCM patients,
      significant correlations were found between APEPc and left atrial backward
      ejection indices (PV-AET: r = -0.49; p < 0.005, PV-IA: r = -0.66; p < 0.001,
      respectively), but not between APEPc and left atrial forward ejection indices.
      CONCLUSION: Augmentation of left atrial afterload may result in decreased left
      atrial forward ejection and increased left atrial backward ejection. Thus, both
      left atrial forward ejection and left atrial backward ejection must be considered
      in the assessment of left atrial ejection performance in patients with
      symptomatic HCM.

PMID- 7807680
TI  - Effect of atrial fibrillation on the fibrino-coagulation system--study in
      patients with paroxysmal atrial fibrillation.
AB  - To clarify the effect of atrial fibrillation (AF) on the fibrino-coagulation
      system, fibrino-coagulation parameters in the paroxysmal period of AF were
      determined in 13 patients with paroxysmal atrial fibrillation (PAF) and compared
      with those in the non-paroxysmal period of AF, and with those in normal subjects.
      Estimated titers of hemoglobin and hematocrit in the paroxysmal period of AF were
      significantly higher than those in the non-paroxysmal period and also higher than
      those in normal subjects. The activated partial thromboplastin time in the
      paroxysmal period was also longer than that in the non-paroxysmal period of AF or
      in normal subjects. However, other estimated parameters, such as prothrombin
      time, fibrinogen, thrombin-antithrombin III, beta-thromboglobulin, platelet
      factor 4, D-dimer and plasmin inhibitor complex, did not show any significant
      deviation. These results conflict with those of previous reports which indicated
      that the fibrino-coagulation system was enhanced in cases of chronic AF. Our
      results suggest that there is no significant activation of the fibrino
      coagulation system, except for obvious hemoconcentration, within the first few
      hours after the onset of PAF. Thus, in terms of the properties of blood
      coagulation, thromboembolism is preventable if antiarrhythmic therapy is
      administered within several hours after the onset of PAF.

PMID- 7807681
TI  - Surgical treatment of ventricular septal defect and its sequelae in adults.
AB  - We operated on 20 adult patients with ventricular septal defect (VSD). In 7 of
      these cases (aged 36 to 51 years, average 42.6 years), VSD was accompanied by
      sequelae other than pulmonary hypertension. Concomitant procedures in type-I VSD
      included a suspension of the prolapsed aortic cusp in 2 patients, a repair of the
      ruptured sinus of Valsalva in 2, and a new procedure for active infective
      endocarditis, described below, in 2. In this latter procedure, the aortic valve
      and infected Valsalva sinus were excised, and the pulmonary valve and the right
      ventricular wall to which the infection had extended were thoroughly debrided.
      The resulting defect was closed with a single patch, and a prosthetic valve was
      inserted in the position of the original aortic valve using this patch as part of
      the annulus. Another patient with the type-II VSD underwent concomitant tricuspid
      valve replacement for infective endocarditis. In the mean follow-up period of
      77.1 months, 6 patients have been doing well in New York Heart Association class
      I, and the remaining patient with Valsalva repair remained in class II due to
      dilated cardiomyopathy.

PMID- 7807682
TI  - Observation of sleep-related breathing disorders in patients with coronary artery
      disease by ambulatory electrocardiogram-respiration monitoring system.
AB  - Eighty-five coronary artery patients examined using an ambulatory
      electrocardiogram-respiration monitoring system (AERMS) in which a respiratory
      sensor was strapped to the right upper abdominal wall. Apnea was defined as a
      cessation of abdominal wall movement lasting at least 10 sec. Sleep-related
      breathing disorder (SRBD) was diagnosed if at least 30 apneic episodes were
      observed during sleep. The cardiac events evaluated during follow-up included
      occurrence of sudden death, myocardial infarction and ventricular tachycardia.
      SRBD was detected in 9 of 85 patients (11%). There were more patients with low EF
      (EF < 50%) in the SRBD group than in the non-SRBD group (p < 0.01). During follow
      up for a mean period of 18.4 +/- 7.6 months after ambulatory recording, four of
      nine (44%) patients in the SRBD group had cardiac events, compared with only four
      of 79 (6%) patients in the non-SRBD group (p < 0.001). Thus, coronary artery
      patients who were complicated with SRBD showed poor cardiac function and had a
      high incidence of cardiac events.

PMID- 7807683
TI  - Effects of hydrocortisone on transmembrane currents in guinea pig ventricular
      myocytes--possible evidence for positive inotropism.
AB  - Steroid hormones are thought to have a positive inotropic action, but the precise
      electrophysiological effects which underlie this positive inotropism remain
      unknown. The effects of hydrocortisone on the L-type calcium current (ICa) of the
      isolated guinea pig ventricular cells were investigated under the whole-cell
      voltage-clamp recording. Hydrocortisone (10(-6) to 10(-5) M) increased the
      amplitude of ICa without any changes in the voltage-dependency in ICa. This agent
      retarded the fast inactivation component of ICa, but not the slow component. On
      the other hand, hydrocortisone slightly reduced the slope conductance of inward
      rectifying potassium current (IK1) at potentials less than -50mV. This effect on
      IK1 is favorable for the activation of ICa. Thus, these results indicate that the
      positive inotropism of hydrocortisone is mediated, at least in part, by a direct
      potentiating effect on ICa.

PMID- 7807684
TI  - The ACE inhibitor alacepril suppresses atherogenesis independent of serum lipids
      in cholesterol-fed rabbits--critical analysis with new ultrasound technique.
AB  - The effects of alacepril, an angiotensin converting enzyme inhibitor, on
      atherogenesis were examined in rabbits fed a hypercholesterol diet. The process
      of atherogenesis was evaluated in vitro by high-resolution transesophageal
      ultrasonography (TEE phi 4 mm, 7.5 MHz), by direct histological examination and
      by serum lipid examination. Of the 38 subjects, 18 were designated as the control
      hypercholesterol group (CH) and 20 received oral alacepril at 90 mg/day (ACE) for
      13-22 weeks. Three rabbits in each group died due to pneumonia. TEE enabled a
      clear diagnosis as either normal, early stage or late stage of atherosclerosis.
      The intimal-medial thickness was significantly less in the ACE group than in the
      CH group, but only over the middle portion of the aorta. The ACE group had a
      smaller area of atheromatous plaque than the CH group (atheromatous index: 37 +/-
      20* and 60 +/- 30% respectively, *p < 0.02). Serum cholesterol and triglycerides
      were similar in the CH group (1590 +/- 653, 258 +/- 224) and the ACE group (1574
      +/- 824, 303 +/- 360 respectively). In conclusion, alacepril reduced both the
      area of atheromatous atheroma plaque and wall hypertrophy independent of serum
      lipids in cholesterol-fed rabbits. In vitro miniature TEE is a dependable method
      for evaluating atherosclerosis in rabbits with hypercholesterolemia.

PMID- 7807685
TI  - Intraventricular changes in the beta-adrenoceptor-adenylate cyclase system of the
      rat heart with the progress of monocrotaline-induced right ventricular
      hypertrophy.
AB  - We investigated the changes in the membranous beta-adrenoceptor-adenylate cyclase
      system in the right ventricle, left ventricle and interventricular septum during
      the progress of monocrotaline-induced right ventricular hypertrophy and failure.
      The beta-adrenoceptor density was decreased in hypertrophied right ventricle 2 to
      4 weeks after treatment. When the rats showed symptoms of right ventricular
      failure 4 weeks after treatment, the beta-adrenoceptor density was decreased in
      the interventricular septum. Both basal and forskolin-stimulated adenylate
      cyclase activities were decreased in the right ventricle at 3 and 4 weeks, and in
      the interventricular septum at 4 weeks, after treatment, which indicates that the
      catalytic activity of adenylate cyclase is reduced. Changes in isoproterenol plus
      Gpp (NH) p- or sodium fluoride-stimulated adenylate cyclase activity were
      generally similar to those in basal activity. These data indicate that a chamber
      specific decrease in beta-adrenoceptor density begins in the early stages of
      right ventricular hypertrophy, and that beta-adrenoceptor density and adenylate
      cyclase activity in the interventricular septum are decreased in the advanced
      stages of heart failure in monocrotaline-treated rats.

PMID- 7807686
TI  - [Significant role of newer quinolone antimicrobials in respiratory tract
      infection: focused on sparfloxacin].

PMID- 7807687
TI  - [Revaluation of current antimicrobials. Series 16: Latamoxef sodium].

PMID- 7807688
TI  - [Revaluation of current antimicrobials. Series 17: Arbekacin sulfate].

PMID- 7807689
TI  - [Revaluation of current antimicrobials. Series 18: Roxithromycin].

PMID- 7807690
TI  - [Clinical studies on clarithromycin dry syrup in the pediatric field. Pediatric
      Study Group of TE-031 Dry Syrup].
AB  - Clarithromycin dry syrup, a new drug preparation, was clinically evaluated in the
      pediatric field and the following results were obtained: 1. Absorption and
      excretion In infants administered with single oral dose of 5 mg (potency)/kg and
      10 mg/kg, the Cmax was 2.26 +/- 0.42 and 3.23 micrograms/ml; Tmax, 1.6 +/- 0.1
      and 2.0 hours; T 1/2, 3.89 +/- 0.52 and 2.06 hours; AUC (0-infinity), 13.48 +/-
      1.93 and 13.84 micrograms.hr/ml, respectively. Urinary concentrations peaked in 2
      4 hours after administration at 5 mg/kg and 0-2 hours at 10 mg/kg. Urinary
      recovery rates in the first 6 hours were 25.8 +/- 3.9% at 5 mg/kg and 20.7% at 10
      mg/kg. 2. Clinical results The clinical efficacy of the drug was evaluated in 150
      patients with various infections. Clarithromycin dry syrup was administered to
      all the patients at daily doses of 10-15 mg/kg divided into 2-3 equal doses. The
      overall clinical efficacy rate was 98.0%, and this drug was effective in 98.9% of
      90 patients for whom the causative pathogens were identified and in 96.7% of the
      other 60 patients for whom the causative pathogens were unknown. The
      bacteriological eradication rate was 88.5%. The efficacy and eradication rates
      for 19 patients who had not responded to previous chemotherapy that lasted for
      more than three days were 94.7% (18/19) and 75.0%, respectively. Side effects
      occurred in 4 (2.4%) of 169 patients subjected to safety analyses, but none was
      serious. As to abnormal laboratory test results, moderate increases of
      eosinophils and elevations of transaminases were observed in 5.9% of the cases.
      No particular and serious problems were associated with administration of this
      drug. Based on the above results, clarithromycin dry syrup is considered to be
      very useful and have a good compliance at a daily dose of 10-15 mg/kg divided
      into 2-3 doses.

PMID- 7807691
TI  - [Clinical usefulness of the combined empirical therapy with flomoxef and
      fosfomycin for intractable respiratory tract infections. With a background of
      increasing MRSA incidence].
AB  - We conducted a multicenter trial to determine the clinical usefulness of the
      combined therapy with flomoxef (FMOX) and fosfomycin (FOM) (FF therapy) as an
      empirical therapy in the treatment of intractable respiratory tract infections,
      because FF therapy has clinically been proved to be very useful for the treatment
      of severe infections including MRSA infections. The overall efficacy rate of FF
      therapy was 69.2%. The efficacy rate for "pneumonia/lung abscess," which occupy
      the largest portions of respiratory tract infections, was 70.0%, showing a
      statistically significant difference from the efficacy rate for FMOX alone
      (56.7%) found in a previous study (P = 0.09 by chi-squared test). Although MRSA
      was eradicated in only 3 cases (37.5%) including superinfection cases, of 8
      patients, from whom MRSA had been isolated as causative organisms, none of our
      patients were superinfected with MRSA. Thus it has been concluded that FF therapy
      is clinically very useful when used as an empirical therapy in the treatment of
      respiratory tract infections.

PMID- 7807692
TI  - [Clinical studies on the time-difference combination therapy with netilmicin and
      minocycline in methicillin-resistant Staphylococcus aureus infections].
AB  - Twenty-eight patients with methicillin-resistant Staphylococcus aureus (MRSA)
      infections were clinically studied for the effectiveness of the time-difference
      combination use of netilmicin (NTL) and minocycline (MINO). The patients were
      treated with NTL 100 mg and two hours later, with MINO 100 mg intravenously,
      twice daily, in the morning and evening for 14 days. Of 26 patients, MRSA was
      eradicated in 16 (61.5%), decreased in one, and unchanged in nine.
      Superinfections occurred with Serratia marcescens and Pseudomonas aeruginosa in
      two patients. The clinical efficacies were assessed in two patients with
      septicemia, 16 with pneumonia, and eight with chronic bronchitis. The obtained
      results were excellent in four patients, good in 15, fair in six, and poor in one
      patient. The rate of effectiveness was 73.1% (19/26). The overall clinical
      effectiveness judged by the committee was good in 19, fair in five, and poor in
      two patients. The efficacy rate was also 73.1% (19/26). Coagulase type II of MRSA
      was found in 23 patients, and coagulase type III in three patients, with overall
      clinical efficacy rates of 73.9% (17/23) and 66.7% (2/3), respectively. A side
      effect of eruption was observed in one patient, and its incidence was 3.6%
      (1/28). Abnormal laboratory test results were observed in 16 patients (57.1%),
      including abnormal liver function in 14 patients, abnormal kidney function in
      three, and increased eosinophils in three. Laboratory abnormalities occurred
      twelve of 16 bedridden patients, and this rate was higher than that in non
      bedridden patients. However, these abnormalities were all mild, transient, and
      immediately recovered after the treatment. In conclusion, the time-difference
      combination therapy using NTL and MINO was effective in the treatment of MRSA
      infections.

PMID- 7807693
TI  - [A comparative study of imipenem/cilastatin sodium BID vs QID in the treatment of
      infections associated with hematopoietic disorders].
AB  - Using the envelope method, we allocated 125 patients with infections accompanied
      by hematopoietic disorders into two groups treated with imipenem/cilastatin
      sodium (IPM/CS) at a daily dose of 1 g/1 g b.i.d. (group BID) or 0.5 g/0.5 g
      q.i.d. (group QID), and obtained the following results. 1. In group BID, ANLL was
      observed in 25 patients; ALL in 6; and NHL in 12. In group QID, ANLL was observed
      in 27 patients; ALL in 7; and NHL in 13. 2. In group BID, efficacy rates were
      54.5% (6/11) in sepsis, 63.0% (17/27) in fever of undetermined origin and 50.0%
      (4/8) in pneumonia, thus the overall efficacy was 61.8% (34/55). In group QID,
      efficacy rates were 66.7% (4/6) in sepsis, 76.0% (19/25) in fever of undetermined
      origin and 35.7% (5/14) in pneumonia, thus the over all was 61.1% (33/54). No
      significant difference in response rates were observed between the two groups. 3.
      Bacteriologically, 22 bacterial strains were isolated in group BID and 21 21
      strains, in group QID. The eradication rates after treatment with IPM/CS was 100%
      in group BID and 66.7% in group QID. 4. Side effects were observed in 8 patients
      in group BID and 3 in group QID. Laboratory examination revealed abnormal values
      in 9 patients in group BID and 6 in group QID. However, all of the side effects
      disappeared after the suspension or discontinuation of IPM/CS. The efficacies of
      IPM/CS therapy for severe infections in patients with hematopoietic disease were
      similar between 1 g/1 g b.i.d. and 0.5 g/0.5 g q.i.d. groups.

PMID- 7807694
TI  - [Bacteria isolated from intraabdominal infection and their susceptibilities to
      antimicrobial agents].
AB  - Bacteria isolated from intraabdominal infections during the period from July 1982
      to June 1993 were investigated with regard to their classifications according to
      a joint research by 9 university hospitals in Japan. The following results were
      obtained. 1. A total of 971 strains were isolated from 684 out of 597 patients
      with peritonitis, and 287 strains out of 971 were isolated from postoperative
      peritonitis. 2. The most predominant organism isolated from patients with acute
      peritonitis was Escherichia coli (28%), followed by Bacteroides fragilis group
      (17%), Gram-positive anaerobic cocci (16%), Enterococcus spp. (9%) and Klebsiella
      spp. (8%). 3. Against E. coli, cefmenoxime, cefuzonam, cefozopran, aztreonam and
      carumonam showed MIC50 less than 0.05 micrograms/ml. Against B. fragilis group,
      erthromycin, clindamycin, imipenem, lincomycin and latamoxef showed MIC50 less
      than 0.78 micrograms/ml. 4. The most predominant organism isolated from patients
      with postoperative peritonitis was Enterococcus spp. (20%) and followed by
      Pseudomonas spp. (14%), and Staphylococcus spp. (13%), E. coli (9%), Enterobacter
      spp. (8%) and Klebsiella spp. (8%). We suggest that cefazolin, cefmetazole,
      flomoxef, cefmenoxime, cefuzonam, and latamoxef are the first choice agents in
      empiric therapy for the treatment of acute peritonitis.

PMID- 7807695
TI  - [In vitro synergistic effects of tazobactam/piperacillin with various
      antibiotics].
AB  - We investigated in vitro synergistic effects of tazobactam/piperacillin
      (TAZ/PIPC), a combination drug of tazobactam (TAZ) and piperacillin (PIPC) in the
      ratio of 1:4, with several other antibiotics against Pseudomonas aeruginosa,
      Serratia marcescens and methicillin-resistant Staphylococcus aureus (MRSA).
      Synergistic effects of TAZ/PIPC with each of tobramycin (TOB), netilmicin (NTL),
      fosfomycin (FOM), ciprofloxacin, minocycline or cefoperazone were observed
      against all bacteria tested in the checkerboard dilution method. No antagonistic
      effect was observed in combination of TAZ/PIPC with other antibiotics. Against P.
      aeruginosa, a combination of TAZ/PIPC with NTL was the most effective, with an
      average fractional inhibitory concentration (FIC) index of 0.459. And a
      combination of TAZ/PIPC with FOM was the most the effective against S. marcescens
      and MRSA. TAZ/PIPC combined with TOB or FOM showed bactericidal effect against P.
      aeruginosa No. 11, S. marcescens No. 39 and S. aureus O-62 at concentrations of
      the drugs that showed only bacteriostatic activity individually. Phase-contrast
      micrographic observations of P. aeruginosa No. 11 and S. marcescens No. 39
      demonstrated that the bacterial cells treated with TAZ/PIPC were in filamentous
      forms and those treated with TOB or FOM were nearly normal. The combination of
      TAZ/PIPC with TOB or FOM induced filamentous cells with spheroplast-like
      structures and lysis. Those results suggest that the combination of TAZ/PIPC with
      aminoglycosides or FOM were useful in the treatment of infections by P.
      aeruginosa, S. marcescens and MRSA, especially those caused by beta-lactamase
      producing strains.

PMID- 7807696
TI  - [A study on MRSA infections and replacement of bacteria. Efficacy of vancomycin
      ceftazidime combination therapy].
AB  - We analyzed the results of bacteriological tests on patients with MASA infections
      admitted to Osaka Prefectural Hospital, for the past 10 years. The conclusions
      obtained are as follows. 1. In our hospital, MRSA infections accounted for 50% or
      more of all Staphylococcus aureus infections in 1983 and 1984 (in the first half
      of the 1980's), markedly decreased to about 10% after 1988, because of the
      preventive measures taken against nosocomial infections and initiation of anti
      MRSA treatment. During the latter period, use of antibiotics including third
      generation cephems was not especially restricted. 2. Glucose non-fermentative
      Gram-negative rods (GNF-GNR) or yeasts co-isolated with S. aureus were more
      frequent in MRSA infected patients, than those in MSSA infected patients. 70 to
      80% of GNF-GNR were P. aeruginosa. 3. Sensitivities of MRSA to drugs were
      studied. VCM was most active, followed by arbekacin and rifampicin. Effectiveness
      against co-isolated GNF-GNR was high with ofloxacin, netilmicin and ceftazidime
      (CAZ). Therefore, is expected that, to prevent the replacement of opportunistic
      infections, combination therapies using vancomycin and CAZ would be effective.

PMID- 7807697
TI  - [Antimicrobial activities of cefditoren against clinical isolates obtained from
      outpatients].
AB  - To examine the antimicrobial activity of cefditoren (CDTR) against strains
      clinically isolated from outpatients at this hospital from November, 1993 to
      February, 1994, the minimum inhibitory concentrations (MICs) were determined
      including those of the control drugs. The results were as follows: 1. CDTR showed
      strong antimicrobial activities against Staphylococcus aureus subsp. aureus,
      Streptococcus pyogenes and Streptococcus pneumoniae. The MICs of CDTR against
      benzylpenicillin-insensitive or -resistant S. pneumoniae distributed in the
      lowest concentration range even compared to those of the control drugs. 2. CDTR
      showed strong antimicrobial activities against Haemophilus influenzae, Moraxella
      subgenus Branhamella catarrhalis, Escherichia coli, and Klebsiella spp. The MIC
      of CDTR against CEPs-resistant E. coli was lower than those of most control
      drugs. 3. Since the microbes described above the major pathogens for the
      community-acquired infections, CDTR will be effective against infectious diseases
      transmitted at outpatient visits.

PMID- 7807698
TI  - [Antibacterial activities of new quinolones against fresh clinical isolates].
AB  - In order to investigate antibacterial activities of new quinolones (NQs) against
      a number of clinical isolates obtained in our laboratory during a period from
      February, 1993 to January, 1994, minimum inhibitory concentrations (MICs) were
      determined using most of the NQs available in the market as of December, 1993.
      The obtained results are summarized as follows: 1. Noticeable differences were
      observed among the antibacterial activities of 8 different NQs tested against
      Gram-positive bacteria, i.e., there were large differences in their MIC
      distributions. Some differences were also observed among different NQs in ratios
      of NQ-resistant strains among Staphylococcus spp. From these results, it seems
      necessary to further study tolerance mechanisms of these Gram-positive bacteria
      toward different NQs and also to examine possible differences in antibacterial
      activities among different NQs against Gram-positive bacteria in clinical
      settings. 2. MIC distributions against Gram-negative bacteria were also different
      among the 8 NQs tested. Though elevated MICs were observed against NQ-resistant
      Gram-negative bacteria in many cases, and somewhat higher, though not exceedingly
      high, MIC values than those against NQ-sensitive bacteria were found in other
      cases, patterns of MIC values against different NQ-resistant Gram-negative
      bacteria were similar for all of the 8 NQs tested. This may explain the fact that
      most of NQ-resistant Gram-negative bacteria showed similar resistant patterns to
      the 8 NQs tested. 3. Among the NQ-resistant bacteria, were found Haemophilus
      influenzae and Neisseria gonorrhoeae strains. Ratios of resistant strains were
      approximately 10% or lower for the former and approximately 20% for the latter.
      4. With MICs of ampicillin and cefaclor used as control, it appears that
      benzylpenicillin (PCG)-insensitive or PCG-resistant Streptococcus pneumoniae
      (PISP or PRSP) and CEPs-resistant Escherichia coli are increasing.

PMID- 7807699
TI  - [Effectiveness of oral treatment with terbinafine in a guinea pig model of tinea
      pedis].
AB  - In order to perform a preclinical evaluation of effectiveness of oral terbinafine
      (TBF) in tinea pedis, an animal model was produced using guinea pigs by
      experimentally infecting the plantar skin with Trichophyton mentagrophytes. TBF
      was administered orally to groups of the infected guinea pigs once-a-day for 4
      consecutive weeks. The therapeutic efficacy was assessed on the basis of recovery
      of fungal cultures from the plantar skin. The group of guinea pigs treated with
      12.5 mg/kg/day of TBF resulted in complete cure. The animal group treated with
      3.13 mg/kg/day of TBF showed significantly better mycological response to the
      therapy than the group treated with 12.5 mg/kg/day of griseofulvin. These results
      suggest clinical usefulness of oral TBF for the treatment of tinea pedis.

PMID- 7807700
TI  - [A study on effectiveness of treatment and prevention of relapse using topical
      administration of terbinafine in a guinea pig model for tinea pedis].
AB  - The effectiveness of topical terbinafine (TBF) to tinea pedis was evaluated an
      animal model in which guinea pigs were experimentally infected through their
      planta pedis with Trichophyton mentagrophytes, then a 1% TBF or butenafine (BTF)
      cream was administered topically once daily for 4 consecutive weeks. The
      therapeutic efficacy was assessed on the basis of recovery of fungal cultures
      from the planta pedis. The cured guinea pigs were reared in a clean environment
      that protected the animals from reinfection. The dermal tissues were cultured 2,
      4, and 8 weeks post-treatment to examine for relapse of tinea. Complete cure was
      achieved after 4 weeks of administration of TBF or BTF cream. In animals
      receiving 4 weeks of treatment with TBF, relapse was not observed up to 8 weeks
      after the termination of treatment. In animals treated with BTF for 4 weeks,
      while no relapse occurred 4 weeks after cessation of the treatment, relapse was
      detected in 2 out of 10 feet at 8 weeks after the termination of treatment. These
      results suggest that topical TBF is effective in curing the infection and in
      preventing relapse in a guinea pig model of tinea pedis.

PMID- 7807702
TI  - [An epidemiologic research design using the Annual of the Pathological Autopsy
      Cases in Japan].
AB  - Epidemiologic research designs using the Annual of the Pathological Autopsy Cases
      in Japan (APAC hereinafter) are discussed in this paper. The APAC data base has
      been recommended for use in epidemiologic research. However, it has not often
      been utilized for such research, even though it covers all pathological autopsy
      cases in Japan, perhaps because of different sampling proportions of each disease
      and because of the dead control series in APAC. First, we present epidemiologic
      measures in using the APAC. We show that the data base can be treated as a case
      control design and that the magnitude of the exposure effect should be estimated
      by an odds ratio. Next, selection bias and information bias in using the APAC are
      discussed. The independence of the control series from the exposure is important
      in the determination of the control disease. Because this design is based on
      internal comparison, non-differential misclassification should be stressed more
      than differential misclassification.

PMID- 7807701
TI  - [A comparative clinical study on flucytosine alone and in combination with
      fluconazole in hematological malignancies: a multicenter study using the envelope
      method].
AB  - Two different flucytosine (5-FC) treatment regimens, one by itself and the other
      in combination with fluconazole (FLCZ) were compared in chemotherapy against
      mycotic infections in 60 patients with hematological diseases. The patients in a
      randomized fashion were assigned to the two treatments. In the combination
      regimen, the two drugs were used in half doses. beta-D-Glucan and D-arabinitol in
      the sera of patients were measured to document mycotic infections, and bacterial
      examinations were also performed. The efficacy of the combination therapy was
      60.0% (18/30) and that of 5-FC alone was 65.5% (19/29). The stratified evaluation
      indicated that no factor was found to contribute to the efficacy in the two
      treatments with statistical significance. The side effects occurred in few cases
      and none of those was serious; including, one case of subjective symptom in each
      groups and two episodes of liver dysfunction in combination treatment. Changes in
      beta-D-glucan concentrations in the sera reflected well the pathophysiology of
      mycotic infections and clinical improvement. These results suggested that a
      combination of 5-FC and FLCZ at half doses provided a clinical benefit comparable
      to 5-FC alone at the ordinary dose, and the safety was considered satisfactory.

PMID- 7807703
TI  - [A 10-year field surveillance in Hinohara Village of Tokyo Prefecture from 1981
      to 1990].
AB  - We conducted a surveillance to clarify the relationship between risk factors for
      diseases of adulthood and lifestyle in a Japanese rural community, Hinohara
      Village, a small village outside of Tokyo. The survey, carried out from 1981 to
      1990 among residents aged 40 and over, comprised physical examination and blood
      chemistry with a questionnaire about dietary intake. Mean systolic blood pressure
      significantly decreased (p < 0.0001) from 140.9 mmHg in 1981 to 132.3 mmHg in
      1990, whereas mean serum total cholesterol, mainly of male examinees, increased
      (p < 0.0001) from 181.4 mg/dl in 1981 to 191.7 mg/dl in 1990. Dietary salt intake
      significantly decreased (p < 0.0001) from 14.3 g/day in 1981 to 12.1 g/day in
      1990. Adjusted mortality rate per 1,000 residents from cerebrovascular disease in
      this village decreased from 1.80 in 1981 to 0.50 in 1990. In contrast to its
      decline, the mortality rates from heart disease, bronchitis/pneumonia and
      neoplasms were 0.40, 0.35 and 0.55 in 1981 and increased to 1.25, 1.10 and 0.64
      in 1990. The prevailing practice of maintaining a low-salt diet might cause the
      decrease of systolic blood pressure, which in turn was thought to decrease the
      mortality rate from cerebrovascular diseases. Although our previous study before
      1981 suggested that total cholesterol was one of the preventive factors against
      cerebrovascular disease, in the present study a preventive effect of cholesterol
      was not substantiated. In contrast, cholesterol is a possible risk factor for
      ischemic heart disease. Thus, a changing pattern of risk factors of diseases of
      adulthood was observed in this village.

PMID- 7807704
TI  - [Correlation between Type A behavior pattern and cardiovascular disease: type A
      and laboratory hyperreactors in Japanese male students].
AB  - The correlation between the Type A behavior pattern (TABP) and cardiovascular
      reactivities was studied in 16 Japanese male students (24.6 +/- 1.7 years). TABP
      was rated in 139 male students in their twenties with a Japanese version of JAS
      Short Form N (J-Q) and a Japanese version of Koskenvuo's questionnaire (K-Q),
      which is modified from Bortner's scale. A preliminary study was requested of
      those whose Type A scores were in the highest third or the lowest third both with
      J-Q and K-Q. After 29 males were recruited, 28 normotensives were invited to
      participate in this study, and 16 of them responded. Physiologic and biochemical
      reactivities to stress tasks (mental arithmetic and cold pressor) were measured
      as predictors of cardiovascular diseases, and the correlation between
      reactivities and TABP scores was examined. Blood pressures and pulse rates were
      monitored by arterial tonometry over the left radial artery with a CBM3000
      (Nippon Colin, Aichi). Blood samples were taken through an 18-gauge butterfly
      needle placed in a left superficial forearm vein. These stress tasks were
      conducted double blindly. There was no relation between TABP scores and
      biochemical reactivities. Both J-Q and K-Q scores, however, correlated moderately
      with reactivities of systolic (r = 0.49 and 0.43, respectively; not significant)
      and diastolic (r = 0.61 and 0.51, respectively; both p < 0.05) blood pressures in
      a cold pressor test. These data support the construct validity of Japanese TABP
      questionnaires, and the author believes in the utility of these questionnaires.

PMID- 7807705
TI  - [Relationship between bacteria decomposing organic substances and water pollution
      in river water].
AB  - In order to clarify the relationship between water pollution and bacteria
      decomposing organic substances, 48 samples of river water were collected at
      twelve stations of the Chikuma-Sai river system. The bacteria decomposing organic
      substances were enumerated and identified by GM plates, which contained fewer
      organic substances than agar plates. Sixteen biological-physicochemical
      examinations of the river water were also performed. The results were as follows:
      temperature and dissolved oxygen in river water influenced the number of bacteria
      decomposing organic substances; proportions of bacteria decomposing degradable
      organic substances were higher in summer and spring than those in winter and
      autumn; the proportions of bacteria decomposing undegradable organic substances
      were higher in winter and autumn than those in other seasons. Organic substances
      were decomposed mainly by Aeromonas, a coliform group of facultatively anaerobic
      Gram-negative rods, and Pseudomonas, Gram-negative aerobic rods. Organic
      substances decomposed by facultatively anaerobic Gram-negative rods were much
      more degradable than those decomposed by Gram-negative aerobic rods. It seemed
      that the bacterial population of Aeromonas and the coliform group in river water
      increased with increases in the effluent of domestic and sewage abundant in
      degradable organic substances. Although Gram-positive rods were hardly isolated
      from river water, most of them decomposed undegradable organic substances. These
      results suggest that most bacteria decomposing organic substances are mainly
      distributed in river water and soil, and that modification of the river
      environment influences self-purification of rivers.

PMID- 7807706
TI  - [The SOS-inhibition activity of human urine investigated by umu-test--diurnal and
      daily changes of SOS-inhibition activity of urine].
AB  - We found that human urine suppressed SOS-responses induced by furylfuramide (AF
      2), as detected by the umu test using Salmonella typhimurium TA1535/pSK1002. In
      the present report, we studied the time stability of the SOS-inhibition activity
      in urine. The diurnal and daily changes of SOS-inhibition in the urine were also
      observed. Results obtained were as follows; 1) SOS-inhibition activity of the
      urine remained stable more than one month after the urine was frozen. 2)
      Individual variation was observed in the SOS-inhibition activity of the urine. 3)
      Total SOS-inhibition activity of per a day showed relatively small variation
      during experimental days. 4) The SOS-inhibition activity of urine was higher
      early in the morning than in the daytime. The activity fell gradually with time
      in the daytime and showed the lowest value in the evening. Then, it rose again at
      night. Therefore, it is necessary to collect urine at specific times to avoid the
      differences caused by diurnal changes in SOS-inhibition activity.

PMID- 7807707
TI  - [Effects of aging on urinary secretion of 3-hydroxyproline and its importance for
      cancer screening in the elderly with ROC analysis].
AB  - OBJECTIVE: to observe the influence of aging on urinary secretion of 3
      hydroxyproline (3-Hyp) in normal subjects and in cancer patients and study the
      effects of aging on the accuracy of urinary 3-Hyp as a general-purpose cancer
      screening test. DESIGN: We reanalyzed, from the aspect of gerontology, the
      amounts of 3-Hyp in the urine samples of the 211 healthy persons and 94 patients
      with cancer reported earlier. The two groups were divided in 3 age subgroups:
      adult, 30 to 44 years, middle-aged, 45 to 64 years, and aged, 65 years and older.
      The cancer stage was separated into 3 categories: stage 1, the early stage
      without any invasion, stage 2, locally invasive with no distant metastasis, and
      stage 3, advanced cancer. The correlation of age and urinary 3-Hyp was analyzed
      in normal subjects and cancer patients. Sensitivity and specificity were
      calculated for different cutoff points in the diverse groups to construct the
      receiver operating characteristic (ROC) curves. MAIN RESULTS: We observed that
      aging decreases the urinary secretion of 3-Hyp in normal subjects, with a
      correlation coefficient of -0.250 (p < 0.001). The mean levels of urinary 3-Hyp
      in patients with cancer were significantly higher than in the normal subjects, p
      = 0.005. The correlation coefficient of urinary 3-Hyp and age was not significant
      (0.100) in cancer patients. The cutoff points of 0.800 mg/g creatinine of urinary
      3-Hyp for persons under 65 years of age and 0.600 mg/g creatinine for persons 65
      years or older were the best thresholds for cancer screening. In the ROC
      analyses, we observed that 3-Hyp has higher accuracy for cancer screening in the
      aged group for all stages together and in the aged and middle-aged for early
      stages of cancer. CONCLUSIONS: The urinary 3-Hyp test was more effective for
      cancer screening in old persons (65 years or older), where cancer is more
      frequent and more difficult to discover. The authors stress the necessity and
      importance of verifying the effectiveness of urinary 3-Hyp for general cancer
      screening in a larger population and in a community set.

PMID- 7807708
TI  - [Bone mineral density of lumbar spine and its relations to biological and
      lifestyle factors in middle-aged and aged Japanese women (Part 2). Effects of age
      and menopause on bone mineral density evaluated by biochemical markers of bone
      metabolism].
AB  - Bone mineral density of the lumbar spine (BMD) and biochemical markers for bone
      turnover were examined to study the mechanisms of age-related and menopause
      related bone loss. We measured BMD of the lumbar spine and serum bone alkaline
      phosphatase (B-AIP) and bone gla-protein (BGP) as markers of bone formation and
      fasting urinary creatinine-adjusted hydroxyproline (Hyp/Cr) and calcium (Ca/Cr)
      as those of bone resorption in 166 community-dwelling Japanese women. A highly
      significant positive correlation between age and each of the biochemical markers,
      except for Ca/Cr, was observed. This relationship was not linear. Marked
      elevation in the levels of the markers was found in women in their sixth decade
      women compared with those in their fifth. All the markers correlated inversely
      with the BMD and these relationships remained significant after elimination of
      the effect of age by partialization. When analyzing the subjects in each five
      year age group, the positive correlation of Hyp/Cr with Ca/Cr was significant in
      the subjects aged 45 to 49 and the negative correlation of Hyp/Cr with BMD was
      significant in those aged 50 to 54. B-AIP correlated positively with BGP in the
      subjects aged between 50 and 54 and inversely with BMD in those aged between 55
      and 59. These correlations were significant. Thus, intercorrelations between the
      markers were observed five years earlier than were correlations between the
      markers and BMD. Such associations appeared earlier in terms of the markers for
      bone resorption than in terms of the markers for bone formation.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7807709
TI  - [Assessment of the mechanical properties of peripheral arteries using
      photosensors and its application].
AB  - I have carried out fundamental experiments to observe the mechanical properties
      of peripheral arteries in healthy subjects using photosensors. To assess the
      mechanical properties, I measured them and evaluated the severity of peripheral
      vascular disturbances in 33 chain saw workers. On the basis of the intrinsic
      volume-pressure relationship in normal arteries, the elasticity was evaluated
      through the vascular volume ratio (V/V0) at which transmural pressure (Ptr) was
      30mmHg. Furthermore, nonlinearity with a clear onset and the maximum point of the
      AC component of the intensity of transmitted light (delta I), with a rapid
      increase of vascular volume around this point, were observed through changes in
      V/V0. This nonlinearity was also observed through changes in relative vascular
      volume (V/VP40) for the reduction rate of cuff pressure (Pc) from systolic blood
      pressure to 40mmHg. The significantly low value of V/V0 (Ptr = 30mmHg) in old
      healthy subjects compared with young subjects suggested that V/V0 (Ptr = 30mmHg)
      tended to decrease with aging. It was impossible to calculate V/V0 because the
      normal nonlinearity was not observed in many measurements for chain saw workers.
      The arterial properties observed in these workers were classified into four types
      based on nonlinear changes: the normal type (Type N); Type I, in which the onset
      and maximum points of delta 1 were detected but V/V0 showed an abnormal value;
      Type II, in which the maximum point was not detected, and Type III, in which it
      was difficult to detect even the onset point. These four types were separated
      from changes in V/VP40 with the reduction of Pc. The classification of severity
      due to arterial opening delay, which was evaluated by changes in V/VP40,
      corresponded to the alternations in nonlinearity in arteries. The results
      obtained in this study indicate that the peripheral vascular disturbance in chain
      saw workers is to be understood as an arterial opening disturbance with the loss
      of normal nonlinearity, in connection with an organic abnormality of arteries.

PMID- 7807711
TI  - [Mirroring on palmar interdigital configurational areas].
AB  - The palmar prints of 902 medical students (732 male and 170 female) were analyzed
      according to the method of Cummins and Midlo, in an attempt to reveal a bilateral
      variance of palmar interdigital configurations within individuals. 1) No sex
      differences were observed in the frequency of true patterns in each interdigital
      area. The overall frequency of true patterns was highest in the fourth
      interdigital area (left 86.7%, right 70.8%) and decreased in the following order:
      the hypothenar area (left 25.6%, right 22.8%), the third interdigital area (left
      12.1%, right 29.7%), the thenar/first interdigital area (left 14.6%, right 4.3%)
      and the second interdigital area (left 0.6%, right 1.2%). 2) Each palmar
      configurational area showed a different frequency of true patterns in the right
      and left hands. In the hypothenar area, the thenar/first interdigital area and
      the fourth interdigital area, true patterns were found most frequently on the
      left hand. On the other hand, true patterns were found most frequently on the
      right hand in the second interdigital area and the third interdigital area,
      especially the frequency of the loop pattern, which was 2.8 times higher in the
      left palm than in the right palm in males, and 2.5 times higher in females. 3)
      The frequency of students who had the same pattern type in both hands was highest
      in the second interdigital area (98.4%) and decreased in the following order: the
      thenar/first interdigital area (88.0%), the hypothenar area (77.9%), the third
      interdigital area (74.1%) and the fourth interdigital area (68.0%).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7807710
TI  - [Effects of crowding on immune functions in mice].
AB  - The effects of several types of crowding on immune functions were studied in
      mice. This study consisted of two experiments. Experiment one: Male BALB/c mice
      were initially housed in groups of four mice per cage. After fourteen days of
      acclimation, the mice were randomly divided into three groups, Control (four mice
      per cage, control group), Crowd-I (four mice per small space) and Crowd-II
      (sixteen mice per cage). These conditions were maintained for seven days. The
      results of experiment one were as follows: (1) The percentage of lymphocytes in
      the blood of Crowd-II was significantly lower than that of Control (p < 0.05).
      (2) The percentage of neutrophils and the absolute number of neutrophils in blood
      of Crowd-II were significantly higher than in Control (p < 0.05). (3) Superoxide
      production activity (NBT reduction activity) of blood neutrophils in Crowd-II
      tended to be depressed, and phagocytic activity of neutrophils was significantly
      depressed in Crowd-II as compared with Control (p < 0.01). These results suggest
      that the complexity of interrelationships among mice caused by an increase in the
      number of animals per cage is a very important stress factor. Experiment two:
      Male BALB/c mice were initially housed in groups of five mice per cage. After
      fourteen days of acclimation, the mice were divided into three groups, Control
      (five mice per cage, control group), Crowd-(1) (five mice per cmall space) and
      Crowd-(2) (twenty mice per cage). In Control and Crowd-(1), the same mice were
      used as in the acclimation period. These conditions were maintained for seven
      days. In this period, on the second day, all the mice were injected
      intraperitoneally with sheep red blood cells (SRBC). The results of experiment
      two were as follows: (1) The specific humoral immune response to SRBC was
      investigated in terms of the number of PFC in the spleens and hemagglutination in
      sera, but significant differences were not found among the groups. (2) Plasma IgG
      levels in the Crowd-(1) were significantly higher than those in Control (p <
      0.05). (3) Both superoxide production activity and phagocytic activity of
      neutrophils were significantly depressed in Crowd-(2) as compared with Control (p
      < 0.01, respectively), whereas each neutrophil function of Crowd-(1) tended to be
      enhanced as compared with Control.

PMID- 7807712
TI  - [Distribution of pulmonary neuroendocrine cells--an immunohistochemical study of
      the lung in autopsied infants including sudden infant death syndrome].
AB  - The distribution of pulmonary neuroendocrine cells (PNEC) was analyzed
      immunohistochemically in 14 victims of sudden infant death syndrome (SIDS), and
      10 cases of infant death unrelated to SIDS, excluding congenital heart disease.
      Lung tissue sections were immunostained with antibodies against chromogranin A
      (CGA), calcitonin (CT) and gastrin-releasing peptide (GRP). CT/GRP
      immunoreactivity decreased in older infants of each group, while CGA
      immunoreactivity showed almost no decrease. Serial section analysis showed some
      PNEC produced CGA, CT and GRP. However, CGA-immunoreactive PNEC sometimes lacked
      of CT/GRP immunoreactivity. The difference of PNEC distribution between SIDS and
      the control cases could not be verified. To date, there have been no studies
      reported of PNEC distribution in infants by using CGA expression. CGA is
      considered to be the most useful marker for detecting PNEC in infant lung. Our
      findings suggest that substances produced by PNEC changed with postnatal
      development both in SIDS and the control group. This result may be one clue to
      clarifying the development and function of small airways in infants, allowing
      further progress in SIDS research.

PMID- 7807713
TI  - Universal probe system for DNA fingerprinting.
AB  - A universal probe system is a combination of an unlabeled primary probe that has
      been inserted in a cloning vector and a labeled secondary probe that is specific
      to the vector. This system is time- and labor-saving in that one does not need to
      label probes every time one uses them, so long as they are inserted in the same
      vector. As a first step in the preparation of a universal probe system for DNA
      fingerprinting, we isolated multi-locus probes from a subgenomic library that had
      been constructed by insertion into the phagemid pUC118 of 1-2 kb fragments of DNA
      from human myeloma cells. Next, we isolated single-stranded DNAs of recombinant
      phagemids, and hybridized them with Southern blots of DNAs from mother-child
      father trios or unrelated individuals. As with double-stranded DNA probes, we
      were able to detect DNA fingerprints, with a commercially available, alkaline
      phosphatase-labeled secondary probe or a digoxigenin-labeled universal sequencing
      primer.

PMID- 7807714
TI  - Efficient amplification of the HLA-DQA1 gene in single genomes using a semi
      nested polymerase chain reaction.
AB  - A semi-nested polymerase chain reaction (PCR) was introduced to amplification of
      the HLA-DQA1 gene, which is a single-copy gene, in a single genome. The
      limitation of template DNA for genotyping is 1 ng of genomic DNA, or more in the
      case of ordinary PCR. When reamplification with the same primers was performed,
      primer dimer was generated and the sensitivity was not improved. We designed a
      semi-nested primer for the second round of PCR, using the semi-nested PCR, more
      than 3 pg of template DNA could be amplified and typed. Furthermore, this method
      was applied to amplify DQA1 gene in single human sperm having haploid DNA, and
      followed by typing with sequence-specific oligonucleotide (SSO) probes. The semi
      nested PCR technique was found to enhance the sensitivity of the amplification
      reaction and allowed the successful typing of the HLA-DQA1 gene. This is helpful
      for genotyping from samples with extremely small amounts of DNA, such as forensic
      or ancient DNA samples.

PMID- 7807715
TI  - Simultaneous measurement of alcohols and hydrogen cyanide in biological specimens
      using headspace gas chromatography.
AB  - We attempted to analyze biological specimens simultaneously for alcohols and
      hydrogen cyanide. A headspace gas chromatographic method with thick film wide
      bore column (PEG 20M) for the simultaneous determinations of methanol, ethanol, n
      propanol and hydrogen cyanide in blood has been developed. This method was
      applied for the determinations of methanol, ethanol and hydrogen cyanide in a
      forensic autopsy case and animal experiments.

PMID- 7807716
TI  - Sudden and unexpected death due to undiagnosed pulmonary thromboembolism in an
      adolescent male without previous history of trauma.
AB  - We report a case of sudden death in a 19-year-old adolescent male who had been
      receiving hospital treatment because of a persistent right calf pain which had
      started about 18 days previously. The pain had not been relieved by analgesics,
      and had extended to the right thigh. The post-mortem examination revealed that
      the cause of death was pulmonary embolism by thrombi which had arisen in the
      right calf veins. The bilateral pulmonary arteries were packed with thrombi, and
      many pulmonary branches were occluded with fresh thrombi. The right calf veins
      contained thrombi of differing ages. In old thrombi, massive collagen formation
      and hemosiderin granules were present but elastic fibers had not yet formed.
      Therefore, it was considered that the old thrombi had formed at the time of the
      patient's first visit to the hospital. The right calf pain for which the deceased
      had sought medical advice was considered to have been caused by the vein
      thrombosis. Although various risk factors for the formation of thrombi are known,
      in the present case no precedent causes other than obesity were identified.

PMID- 7807717
TI  - Sex identification of old skeletal remains by DNA analysis: the report of three
      cases.
AB  - We analyzed the DNA in the remains of three skeletons affected by severe post
      mortem modification to identify the sex of the cases. We analyzed DNA extracted
      from bone, bone marrow and a tooth by Southern blot hybridization with Y
      chromosome specific probe and PCR to amplify the sex chromosome specific
      sequence. The first case had been preserved underground in a deep grave for two
      months, the second case was found in a forest after more than five years, and the
      last case had been kept in a styrofoam box for few years. The detective
      sensitivity of Southern hybridization improved to nearly the same level as PCR
      with the aid of computed image processing. Although PCR was of obvious benefit
      when analyzing small amounts of biological evidence, amplification was impossible
      in case the target sequence became lost or changed. As a result, we identify the
      sexes of the three cases by Southern blot hybridization or PCR using bone, bone
      marrow and tooth DNA. The old skeletal remains were suitable for sex
      identification in spite of severe post-mortem change, due to preservation in a
      condition protected from external influences.

PMID- 7807718
TI  - [New semi-automatic ROI setting system for brain PET images based on elastic
      model].
AB  - We have developed a semi-automatic ROI setting system for brain PET images. It is
      based on the elastic network model that fits the standard ROI atlas into
      individual brain image. The standard ROI atlas is a set of segments that
      represent each anatomical region. For transformation, the operator needs to set
      only three kinds of district anatomical features: manually determined midsagittal
      line, brain contour line determined with SNAKES algorithm semi-automatically, a
      few manually determined specific ROIs to be used for exact transformation.
      Improvement of the operation time and the inter-operator variance were
      demonstrated in the experiment by comparing with the conventional manual ROI
      setting. The operation time was reduced to 50% in almost all cases. And the inter
      operator variance was reduced to one seventh in the maximum case.

PMID- 7807719
TI  - [Comparison between 123I-BMIPP and 201TlCl myocardial imaging by circumferential
      profile analysis in patients with myocardial infarction--evaluation of effects of
      vascular reconstruction in patients with myocardial infarction].
AB  - We quantitatively evaluated the effects of vascular reconstruction according to
      the stage by 123I-BMIPP and 201TlCl using circumferential profile (CP) curve
      method in patients with myocardial infarction. (1) Comparison of the CP curves
      for the two nuclides in normal volunteers (n = 9) showed no difference in
      distribution. (2) In patient with myocardial infarction (n = 32) the severity
      score was evaluated using the CP curves obtained in the normal volunteers. Type B
      (marked decrease in 123I-BMIPP accumulation) accounted for 83% in the group in
      whom vascular reconstruction was performed in the acute stage (Group I) and 91%
      in the group in whom vascular reconstruction was performed in the chronic stage
      (Group II). On the other hand, type E (similar accumulation between the two
      nuclides) accounted for 79% in the group in whom vascular reconstruction was
      unsuccessful or was not performed (Group III). The severity score for each
      nuclide did not significantly differ among Group I, II and III. The 123I
      BMIPP/201TlCl ratio was the highest in Group II, followed in order by Group I and
      Group III (p < 0.05). The assessment of the ratio of "severity scores" for both
      nuclides is considered to be useful for evaluation of the surviving myocardium,
      rather than the assessment of a single nuclide.

PMID- 7807720
TI  - [Initial myocardial uptake and myocardial clearance of 123I
      metaiodobenzylguanidine in patients with ischemic heart disease of left
      ventricular dysfunction and dilated cardiomyopathy].
AB  - We studied initial myocardial uptake and myocardial clearance of 123I
      metaiodobenzylguanidine (MIBG) in patients with ischemic heart disease of left
      ventricular dysfunction and dilated cardiomyopathy. Eleven patients with ischemic
      heart disease of left ventricular dysfunction (IHD group), 6 patients with
      dilated cardiomyopathy (DCM group) and 7 control cases (control group) were
      studied. Heart to mediastinum activity ratio (H/M) of early and delayed image was
      significantly lower in the IHD and DCM groups than in the control group. Although
      initial myocardial uptake of MIBG showed no significant difference among three
      groups, myocardial clearance of MIBG was significantly higher in the IHD (35 +/-
      11%) and DCM (48 +/- 13%) groups than that in the control group (19 +/- 10%). H/M
      of delayed image was related to the left ventricular size, initial MIBG uptake
      and MIBG myocardial clearance. Negative correlation was observed between MIBG
      myocardial clearance and left ventricular ejection fraction in all cases. In
      conclusion, initial myocardial uptake of MIBG were not decreased in patients with
      IHD and DCM. Enhanced myocardial clearance of MIBG was observed not only in
      patients with DCM but also in patients with IHD.

PMID- 7807721
TI  - [Clinical evaluation of patients with right ventricular infarction detected by
      dual SPECT imaging of thallium-201 and technetium-99m pyrophosphate].
AB  - We evaluated clinical significance of dual-nuclide SPECT imaging (D-SPECT) of
      thallium-201 and technetium-99m pyrophosphate (PYP) in patients of acute inferior
      left ventricular infarction with PYP uptake in the right ventricle (PYP (+)
      group) in comparison with those without PYP uptake (PYP (-) group). There was no
      difference in coronary risk factors, history of angina, blood pressure, heart
      rate, and hemodynamics on admission between PYP (+) group and PYP (-) group. The
      duration from onset to admission was longer in PYP (+) group and coronary
      reperfusion therapies were carried out in few cases. In 7 of 8 PYP-positive
      patients, the diagnosis of right ventricular infarction was made only by D-SPECT.
      Four of 8 were complicated with shock within three days, and the duration of
      hospitalization was longer. Coronary angiography demonstrated many proximal
      lesions (50%) in PYP (+) group but few ones (18%) in PYP (-) group. D-SPECT was
      very useful for diagnosing acute right ventricular infarction, and it might
      contribute to the prevention of shock if performed within a few days.

PMID- 7807722
TI  - [Circulation time determined by carotid angiography in patients with chronic
      internal carotid artery occlusion: comparison with cerebral blood flow and oxygen
      metabolism measured by PET].
AB  - The degree of collateral circulation in patients with unilaterally chronic
      internal carotid artery occlusion was estimated by mean transit time of contrast
      material in rapid sequence carotid angiography (Angiographic MTT), and compared
      with cerebral blood flow and oxygen metabolism measured by PET. In normal density
      region on X-ray CT, a significant negative correlation was observed between
      Angiographic MTT and cerebral blood flow (CBF). This indicates that cerebral
      blood flow can be estimated by Angiographic MTT. It has been reported that the
      ratio of cerebral blood volume (CBV) to CBF (CBV/CBF), i.e., mean transit time
      determined by PET well agreed with OEF, and is good indicator for brain
      circulation reserve. In this study, no significant correlation was observed
      between Angiographic MTT and CBV/CBF. However, a significant positive correlation
      was observed between Angiographic MTT and oxygen extraction fraction (OEF), and
      no significant correlation was observed between Angiographic MTT and oxygen
      consumption rate (CMRO2). These indicates that Angiographic MTT may be indicator
      for brain circulation reserve.

PMID- 7807723
TI  - [Assessment of left ventricular count increase with ECG-gated 99mTc-MIBI SPECT
      using a single-head rotating gamma-camera].
AB  - ECG-gated 99mTc-MIBI SPECT was performed in 33 patients, including 17 normal
      subjects and 16 patients with old myocardial infarction. To compare the findings
      by echocardiography (UCG), regional wall motion was qualitatively assessed by
      cine-mode display and quantitatively measured as an increase in regional count
      from end-diastole to end-systole. The percent count increase and relative count
      increase was measured to display on the Bull's eye polar map. In the study of
      normal subjects, the count increase was greater in apical regions and smaller in
      septal regions. Regional wall motion by this method correlated well with UCG
      findings (agreement: 97%, complete agreement: 60%). A mild but significant
      correlation was observed between the count increase by this method and the
      percent wall thickening by UCG. We conclude that regional wall motion can be
      accurately evaluated with ECG-gated 99mTc-MIBI SPECT, which thus permits
      simultaneous assessment of regional wall motion and myocardial perfusion.

PMID- 7807724
TI  - [Assessment of pulmonary ventilation/perfusion ratio by dual radionuclides SPECT
      using 81mKr gas and 99mTc-MAA].
AB  - The accuracy and clinical availability of pulmonary ventilation/perfusion (V/Q)
      ratio images by 81mKr gas and 99mTc-MAA dual radionuclides SPECT was assessed in
      10 normal volunteers and 31 patients with pulmonary diseases. After equalizing
      the total acquisition counts of both radionuclides, the ratio of 81mKr/99mTc
      count was calculated in each pixel and expressed as the functional map of V/Q.
      Then, the histogram of pixel numbers against V/Q ratio was drawn and the center
      of weight (CW) and standard deviation (SD) of the distribution were determined.
      The reproducibility of this method was excellent. In normal volunteers, CW was
      1.07 and the SD was 0.25. The V/Q was lower in dorsal than in the ventral
      portion. SD was large and lobar or segmental high V/Q areas were clearly noted in
      the patients with pulmonary vascular diseases. In pulmonary emphysema, large low
      V/Q areas coexisted with patchy high V/Q areas. CW was small and SD was large in
      this group. There was a significant positive correlation between SD and PA-aO2.
      The author believes that the pulmonary ventilation/perfusion (V/Q) ratio images
      by dual radionuclides SPECT is a useful diagnostic procedure. Further, SD
      determined by this examination is thought to be a good parameter of uneven
      distribution of pulmonary ventilation and perfusion.

PMID- 7807725
TI  - [Quantifying regional cerebral blood flow with N-isopropyl-p
      [123I]iodoamphetamine and SPECT by one-point sampling method].
AB  - We developed a new non-invasive technique; one-point sampling method, for
      quantitative measurement of regional cerebral blood flow (rCBF) with N-isopropyl
      p-[123I]iodoamphetamine and SPECT. Although the continuous withdrawal of arterial
      blood and octanol treatment of the blood are required in the conventional
      microsphere method, the new technique does not require these two procedures. The
      total activity of 123I-IMP obtained by the continuous withdrawal of arterial
      blood is inferred by the activity of 123I-IMP obtained by the one point arterial
      sample using a regression line. To determine when one point sampling time was
      optimum for inferring integral input function of the continuous withdrawal and
      whether the treatment of sampled blood for octanol fraction was required, we
      examined a correlation between the total activity of arterial blood withdrawn
      from 0 to 5 min after the injection and the activity of one point sample obtained
      at time t, and calculated a regression line. As the results, the minimum % error
      for the inference using the regression line was obtained at 6 min after the 123I
      IMP injection, moreover, the octanol treatment was not required. Then examining
      an effect on the values of rCBF when the sampling time was deviated from 6 min,
      we could correct the values in approximately 3% error when the sample was
      obtained at 6 +/- 1 min after the injection. The one-point sampling method
      provides accurate and relatively non-invasive measurement of rCBF without octanol
      extraction of arterial blood.

PMID- 7807726
TI  - [Evaluation of myocardial viability and efficacy of reperfusion therapy by dual
      SPECT using 99mTc-PYP and 201Tl in acute myocardial infarction].
AB  - Dual SPECT using 99mTc-PYP and 201Tl was performed in 70 patients with acute
      myocardial infarction, and the ratio of overlap zone between 201Tl and 99mTc-PYP
      uptake in the infarcted area was determined (the Y-ratio). The Y-ratio was
      significantly higher in the group with redistribution in the infarcted area on
      exercise thallium myocardial scintigraphy in the chronic stage of infarction, as
      well as in the group with normal left ventricular wall motion. Thus, the Y-ratio
      value was apparently useful in the evaluation of myocardial viability. Patients
      from 60% of the Y-ratio upward are suggested that myocardial viability had been
      survived. When the Y-ratio was determined in 30 patients who underwent early
      reperfusion therapy (ICT or direct-PTCA), no significant difference was found
      between the ICT group and the direct-PTCA group. However, the Y-ratio was
      significantly higher when reperfusion was performed within 6 hours than when it
      was performed after 6 hours, and a significant positive correlation (r = 0.63, p
      < 0.01), was found between reperfusion time from cardiac event within 9 hours and
      the value of (100--the Y-ratio). CONCLUSION: The Y-ratio was grateful appeared to
      be useful for the quantitative evaluation of myocardial viability in the acute
      stage of myocardial infarction. In addition, it appears to be important to
      perform reperfusion as soon as possible to improve myocardial salvage.

PMID- 7807727
TI  - [Usefulness of 99mTc-PMT SPECT and 18F-FDG PET in diagnosing orbital metastasis
      of hepatocellular carcinoma].
AB  - We reported a case in which 99mTc-PMT scintigraphy was useful in diagnosing
      orbital metastasis of HCC. The case involved a 70 y.o. male, who had undergone
      nine transcatheter arterial embolizations over two years because of HCC and who
      had a past history of gastric cancer. The patient had complained of headache and
      visual disturbance for two months. Cranial CT and MRI studies showed a large
      homogeneous mass with remarkable bone destruction in the right lateral orbital
      wall. Because AFP was elevated, orbital metastasis of HCC was suspected, and
      99mTc-PMT scanning was performed. On the planar and SPECT images, very high
      uptake was found in the right orbital tumor. The FDG-PET study showed remarkable
      hypermetabolism in the medial portion of tumor and follow-up MRI revealed that
      the tumor had expanded and invaded to the medial side of the orbit. 99mTc-PMT
      scanning was critical in diagnosing this case of orbital metastasis, and FDG-PET
      imaging was useful in determining the most active portion of the tumor.

PMID- 7807728
TI  - [Detection and localization of multiple metastases from differentiated thyroid
      carcinoma with 99mTc-MIBI whole body scintigraphy: a case report].
AB  - A 79-year-old male with a history of total thyroidectomy due to follicular
      thyroid carcinoma developed multiple metastases in the lung, bone, and lymph
      nodes. In order to detect and localize every metastases, 99mTc-MIBI whole body
      scintigraphy was performed, and clearly depicted all metastatic lesions except
      tiny pulmonary nodules. 99mTc-MIBI whole body scintigraphy may be useful in
      detecting metastases from differentiated thyroid carcinoma, because of a good
      quality of scintigram and no need of patient preparation. This article is the
      first report on 99mTc-MIBI localization in multiple metastases from
      differentiated thyroid carcinoma.

PMID- 7807729
TI  - [The effect of stellate ganglion block on the local and global cardiac uptake of
      123I-metaiodobenzylguanidine].
AB  - To investigate the effect of stellate ganglion block (SGB) on the cardiac uptake
      of 123I-metaiodobenzylguanidine (MIBG), four patients without heart disease
      underwent SGB. Studies were done twice: once with SGB and once without SGB.
      Anterior planar images and myocardial SPECT images were taken at 10 minutes and
      60 minutes after MIBG injection both with and without SGB. Cardiac uptake of MIBG
      on planar images estimated by heart/liver ratio was significantly higher with SGB
      at both imaging times (p < 0.01, p < 0.05) than without SGB. SGB had no effect on
      the local uptake of MIBG on SPECT images. In conclusion, SGB did not change the
      local cardiac uptake of MIBG, but it appeared to increase the global myocardial
      uptake of MIBG.

PMID- 7807731
TI  - Proceedings of the 27th Annual Meeting of the Japanese Epilepsy Society.
      Hirosaki, October 1-2, 1993.

PMID- 7807730
TI  - [A longitudinal study of CMRGlu in dementia of Alzheimer type].
AB  - We studied the serial changes of CMRGlu in 6 patients with dementia of Alzheimer
      type. All patients demonstrated moderately severe dementia at the initial PET
      scan. Serial PET scans were performed at an interval of 12 to 24 months. Five of
      the 6 patients showed a deterioration of clinical symptoms at the second scan.
      The global CMRGlu serially decreased in all patients. An asymmetry of CMRGlu in
      both the frontal and parietal regions was observed at the initial PET scan, while
      the direction of asymmetry was preserved at the second PET scan. The ratios
      (frontal/parietal and parietal/striatum) of CMRGlu showed no interval change.
      Therefore, CMRGlu was considered to decrease progressively throughout the entire
      brain in patients with moderately severe dementia of Alzheimer type.

PMID- 7807732
TI  - Sociomedical aspects of temporal lobe epilepsy.

PMID- 7807733
TI  - Postictal psychoses: in comparison with acute interictal psychoses.

PMID- 7807734
TI  - Clinical approach to psychotic symptoms in temporal lobe epilepsy: vulnerability
      hypothesis of "epileptic psychosis".

PMID- 7807735
TI  - Temporal lobe epilepsy of childhood onset.

PMID- 7807736
TI  - Improvement of quality-of-life following resective surgery for temporal lobe
      epilepsy: results of patient and family assessments.
AB  - In order to evaluate the quality-of-life (QOL) of epilepsy surgery patients, we
      surveyed patients' degree of life satisfaction and their families' degree of
      satisfaction with patient's status in a range of domains both pre- and post
      operatively. Of 100 patient-family sets of surveys that were mailed out, 93 were
      completed and returned from patients and 91 from their families. All patients
      surveyed had temporal lobe epilepsy and had been followed for longer than 2 years
      after resective surgery. Patients and their families rated overall QOL as having
      markedly improved following surgery. However, they rated social domains of QOL,
      including role activities, financial status, and social and family relationships
      as having improved relatively little. Despite freedom from seizures, a few
      patients' families were dissatisfied with the patients' post-operative status,
      primarily for psychosocial reasons. Patients operated on at a later age reported
      little gains in life satisfaction following surgery. This study supports the
      conclusion that surgical intervention should occur before patients are subjected
      to the psychological conflicts and social handicaps associated with chronic
      intractable epilepsy.

PMID- 7807737
TI  - Neuropathology of temporal lobe epilepsy.

PMID- 7807738
TI  - Discontinuation of antiepileptic drug in childhood epilepsy: evaluation of the
      differences between epileptic syndromes.

PMID- 7807739
TI  - Guidelines for discontinuation of antiepileptic drugs for childhood absence
      epilepsy and rolandic epilepsy.

PMID- 7807740
TI  - A retrospective study on discontinuation of antiepileptic drugs following seizure
      remission.

PMID- 7807741
TI  - Discontinuation of antiepileptic drug treatment in controlled seizure patients.

PMID- 7807742
TI  - A long-term follow-up and clinical study of epileptics whose medication was
      terminated.

PMID- 7807743
TI  - Angelman syndrome in three siblings: genetic model of epilepsy associated with
      chromosomal DNA deletion of the GABAA receptor.

PMID- 7807744
TI  - Regional differences of immediate early gene expressions in the brain of El mice
      as examined with development and seizure history.

PMID- 7807745
TI  - Effects of repeated immunosuppressant treatment on rat pentylenetetrazol-induced
      convulsion.

PMID- 7807746
TI  - Modulation of endogenous ADP-ribosylation in the kindling model of epilepsy.

PMID- 7807748
TI  - Proceedings of the 8th Workshop for the Clinical Research on Chronobiology.
      Kyoto, September 30-October 1, 1993.

PMID- 7807747
TI  - Excitatory changes of rat perirhinal cortex by amygdala-kindling: a study with in
      vitro slice technique.

PMID- 7807749
TI  - [Pulmonary hemodynamics during oxygen non-inhalation in patients with home oxygen
      therapy].
AB  - We examined the effects of the stopping of oxygen inhalation on pulmonary
      hemodynamics in 19 patients with stable chronic cor pulmonary with 1 year of Home
      Oxygen Therapy (HOT). All patients were classified into two groups in which
      hemodynamic examination was performed under oxygen inhalation (Group A; 10) or
      under air breathing from 4 hours before examination (Group B; 9). The hemodynamic
      examination was repeated after 2 hours of stopping oxygen inhalation in Group A,
      and was repeated 2 hours after restarting oxygen in Group B. The mean pulmonary
      arterial pressure (mPAP) decreased significantly from 25.2 +/- 7.2 Torr before
      HOT to 20.4 +/- 3.2 Torr after 1 year of HOT, and then increased to 27.6 +/- 5.6
      Torr after stopping oxygen. In contrast, mPAP in Group B did not change: 32.9 +/-
      9.4 Torr before HOT, 29.4 +/- 8.2 Torr during stopping of oxygen and 27.6 +/- 5.6
      Torr 2 hours after restarting oxygen after 1 year of HOT. These findings suggest
      that stopping oxygen inhalation in patients with long-term HOT can markedly
      affect pulmonary hemodynamics as well as the prognosis.

PMID- 7807750
TI  - [Role of eosinophils and cell adhesion molecules in the asthmatic response to
      allergen].
AB  - To evaluate the eosinophil infiltration in lung tissues in asthmatic responses of
      Brown-Norway rats and guinea pigs, both of which were sensitized with ovalbumin
      (OA), the time course of changes in respiratory impedance (Zrs) and eosinophil
      influx after aerosol challenge with OA were measured. The effect of treatment
      with monoclonal antibody (MoAb) 1A29 against rat intercellular adhesion molecule
      1 (ICAM-1) alone and a mixture of MoAb 1A29 and MoAb WT-3 against rat CD18 on
      asthmatic responses of the rats was studied. Finally, these expressions in lung
      tissues of the rats were recognized. The number of eosinophils in the
      subepithelial area was counted in sections of lung tissue stained with Giemsa's
      solution, using an Interaktive Build-Analyse System (IBAS). All of the rats and
      80% of the guinea pigs developed an increase in Zrs 6-7 hours after challenge,
      indicating that these animals showed a late asthmatic response (LAR). The rats
      and the guinea pigs with a LAR had higher eosinophil counts than those with an
      immediate asthmatic response and sensitized, non-challenged animals (p < 0.01).
      The rats treated with MoAb 1A29 alone (n = 5) and a mixture of MoAb 1A29 and MoAb
      WT-3 (n = 8) developed significantly smaller increases in Zrs and a smaller
      eosinophil influx than the control animals treated with phosphate buffered saline
      (n = 15): 147.3 +/- 3.5, 134.8 +/- 11.6 versus 158.8 +/- 6.3% of baseline; 734 +/
      21, 545 +/- 108 versus 1006 +/- 147 cells/mm2 (p < 0.01). Immunoperoxidase
      staining of rat lung tissues using MoAb 1A29 or MoAb WT-3 was performed ICAM-1
      immunoreactivity was positive in the basilar portion of the epithelium, in the
      vascular endothelium of the trachea and in the pulmonary vascular endothelium.
      ICAM-1 immunoreactivity was revealed to be upregulated after challenge. The
      number of CD18-positive cells in the trachea and in the subepithelial area
      increased after challenge. These results show that eosinophil infiltration
      corresponds closely to bronchoconstriction in LAR and that treatment with MoAbs
      to ICAM-1 and CD18 may be effective in reducing asthmatic symptoms.

PMID- 7807751
TI  - [Different responses of morning dipping and nocturnal dipping to inhaled and/or
      oral steroids in chronic asthmatics].
AB  - Clinical experiences have suggested distinct differences in responses to anti
      asthmatic drugs between patients suffering early morning asthmatic attacks and
      those experiencing nocturnal ones. However, there has been no report on any
      difference in the improvement of asthmatic flow dipping after inhaled and/or oral
      steroid treatment. In this retrospective study, the peak expiratory flow rates
      (PEF), which had been monitored four times a day, were reviewed in 40 chronic
      asthmatics. The group consisted of 19 patients with very low PEF (geometrical
      mean PEF/week [mPEF] < 60% of the personal best PEF), 15 patients with moderately
      low PEF (mPEF 60% to 70% of personal best PEF), 2 patients with mildly low PEF
      (mPEF 70% to 80% of personal best PEF) and 4 patients with occasionally low PEF
      (mPEF > 80% of personal best PEF). Of 40 chronic asthmatics, 22 patients had
      morning dipping alone and 10 patients had both morning dipping and nocturnal
      dipping. After inhaled and/or oral steroid treatment at sufficient level, mPEF
      was improved in all patients. All the dipping disappeared except for morning
      dipping in five cases. We concluded that there was a difference in responses to
      inhaled and/or oral steroids during early morning dipping and during nocturnal
      dipping in chronic asthmatics. There should be further investigation to
      discriminate between pathophysiological events that may be related to morning
      dipping and to nocturnal dipping.

PMID- 7807752
TI  - [High oxygen breathing improves inhomogeneities of ventilation-perfusion
      distributions in acutely injured lungs].
AB  - Using twenty-five mongrel dogs either with or without alveolar flooding induced
      by oleic acid administration, the effects of high oxygen breathing (60% O2) on
      ventilation--perfusion (VA/Q) distributions in the lungs were systematically
      investigated. VA/Q distributions were examined by multiple inert gas elimination
      technique, from which the VA/Q values describing mean positions of perfusion (Q)
      and ventilation (VA) distributions against the VA/Q axis were calculated (mean Q
      and mean VA). As the first measure of dispersion for VA/Q distribution, the log
      standard deviation was estimated (log SD (Q) and logSD (VA)). As the second
      measure of dispersion, the area under the curve, constructed by plotting inert
      gas arterial-to-alveolar partial pressure differences as a function of blood-gas
      partition coefficient, was calculated (aAD area). High oxygen breathing slightly
      enhanced the dispersion of VA/Q distributions in the normal dogs but decreased
      that in the dogs injured with oleic acid. Therefore, we concluded that high
      oxygen breathing worsened the inhomogenieties of VA/Q distributions in normal
      lungs but did improve those in acutely injured lungs.

PMID- 7807753
TI  - [Detection of Mycobacterium tuberculosis in transbronchial biopsy specimens by
      polymerase chain reaction].
AB  - Polymerase chain reaction (PCR) for the rapid detection of Mycobacterium
      tuberculosis was used to test 30 clinical specimens (transbronchial biopsy
      specimens) from patients in whom tuberculosis was suspected on chest X-ray. In
      these patients, 15 cases were histologically diagnosed as tuberculosis. Among
      them, M. tuberculosis was detected in 8 specimens by PCR. Of 8 PCR positive
      specimens, 7 were also positive by smear and culture; the other was negative by
      smear and positive by culture. On the other hand, 15 cases were therapeutically
      diagnosed as the tuberculosis and these specimens showed negative results in
      neither PCR nor microbiological tests. We conclude that the PCR method is useful
      for rapid and direct detection of M. tuberculosis in transbronchial biopsy
      specimens.

PMID- 7807754
TI  - [Treatment modalities and hypothalamo-pituitary-adrenal (HPA) axis suppression in
      Japanese patients with asthma].
AB  - We examined HPA axis function using a short tetracosactrin test in 94 asthmatics
      treated with three different modalities. The first group, (B + S), consisted of
      41 patients taking BDP (910 +/- 320 micrograms, daily) plus a short term burst of
      oral steroids (20-40 mg daily, 3-7 days/course, 1-18 courses/year). The second
      group, (B + R), consisted of 19 patients taking BDP (1076 +/- 410 micrograms,
      daily) plus continuous oral steroids (2.5-20 mg/day for 1.8-24 years). The third
      group, (B alone), consisted of 34 patients taking BDP only (615 +/- 258
      micrograms, daily). All patients had been inhaling BDP for more than 1 year. The
      rise in cortisol in response to tetracosactrin in B + S, B + R, and B alone was
      12 +/- 4.3 micrograms/dl, 7.0 +/- 5.0 micrograms/dl and 14 +/- 4.5 micrograms/dl,
      respectively, and achieved cortisol was 21 +/- 4.5 micrograms/dl, 12 +/- 7.2
      micrograms/dl and 23 +/- 4.2 micrograms/dl;, respectively. Both values were
      significantly lower in the B + R group than in either B + S or B alone. However,
      there was no difference between B + S and B alone, although the BDP dose was
      significantly larger in the B + S group. Significant HPA axis suppression (rise
      in cortisol < 7 micrograms/dl and achieved cortisol < 18 micrograms/dl) was seen
      in 7 patients. Although HPA axis suppression was more frequently seen in B + R
      (10/19), no significant difference was seen between B + S and B alone (4/41 and
      1/34, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7807756
TI  - [A case of bronchiolitis obliterans organizing pneumonia: diagnostic utility of
      bronchoalveolar lavage and CT scan].
AB  - A 54-year-old female was admitted to our hospital because of abnormal shadows on
      chest X-ray at annual checkup. She complained of dyspnea on exertion. Chest X-ray
      findings showed an increase in density at the bilateral lower lung fields and
      unclearness of the silhouette of the heart and the diaphragm. CT scan findings
      revealed irregular opacities of various density with many small cystic changes
      and air bronchograms and air bronchiolograms. The pulmonary function test showed
      restrictive ventilatory disturbance and reduced diffusing capacity. BALF findings
      revealed an increase in the total cell count, an increase in the percentage of
      lymphocytes and a decrease in the OKT4+/OKT8+ ratio. TBLB specimen showed
      infiltration of mononuclear cells in alveolar septa and organizing exudate in
      alveolar ducts. These findings suggested a diagnosis of BOOP rather than IPF, and
      an open lung biopsy was performed. Open lung biopsy specimen showed obstructive
      bronchiolitis with polypoid granulation tissue and thickening of alveolar septa
      with infiltration of mononuclear cells, and she was diagnosed as having BOOP. She
      responded well to corticosteroid and is free from any abnormalities on chest X
      ray, CT scan and pulmonary function test at present. Analysis of BALF and CT scan
      findings are useful for the differential diagnosis of BOOP and IPF.

PMID- 7807755
TI  - [Outpatient drainage treatment for simple spontaneous pneumothorax].
AB  - Spontaneous pneumothorax has been managed on an outpatient basis by intercostal
      tube drainage and a portable flutter valve device (pneumothorax set). In a series
      of 111 selected patients, from 14 to 75 years of age, who had no complaints such
      as dyspnea, had neither tension-nor hemo-pneumothorax, and could promptly return
      to hospital in an emergency, intercostal tube insertion and continuous negative
      pressure drainage were instituted at the outpatient department. After
      approximately one hour of suction, if an air leak ceased and the lung was re
      expanded, the patient was allowed to return home with a pneumothorax set
      connected to the chest tube. But, if an air leak persisted, they were admitted to
      hospital. The outpatients were followed every 2 or 3 days thereafter, and if
      their course was uneventful, the chest tube was removed a week later. If the
      onset of lung recollapse was seen at outpatient check up, hospitalization was
      required. Outpatient treatment was successful in 81 cases (72.9%) of the series.
      However, 14 patients were hospitalized because of persistent air leak at the
      outpatient room, and 5 were admitted because of wound pain, re-expansion edema or
      other reasons. During the ambulatory course, 11 were admitted to hospital with
      recollapse of the lung. Bacterial cultures of drain tips were positive in 22.6%
      of 75 examined cases, which was a higher percentage than that associated with
      inpatient drainage. Wound infection with St. aureus occurred in one case after
      removal of the drain.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7807757
TI  - [The pulmonary air meniscus sign in a case of sclerosing hemangioma].
AB  - A 57-year-old woman was admitted to our hospital because of a slowly growing
      pulmonary tumor with a 34 year history. Chest roentgenogram on admission showed a
      42 mm sharply demarcated solitary tumor in the left upper lobe. Chest CT revealed
      a slit-like pulmonary air meniscus. Left upper lobectomy was performed. A
      specimen from the resected lung histologically showed solid, papillary and
      hemorrhagic patterns, and the diagnosis of pulmonary sclerosing hemangioma was
      therefore made. Pulmonary air meniscus sign in pulmonary sclerosing hemangioma is
      rare. We think one possible mechanism in the production of an air meniscus sign
      in sclerosing hemangioma is bleeding in communication with a bronchus.

PMID- 7807758
TI  - [A case of HTLV-1 carrier associated with pulmonary cryptococcosis and thymoma].
AB  - A 46-year-old female was admitted to our hospital on December 1991 for further
      examination of an abnormal shadow on chest X-ray. A huge mass in the upper
      mediastinum and a thin-walled cavitary lesion in the right upper lobe were found
      by chest radiography and computed tomography. On March 2, 1992, surgical
      resection was performed with pathological diagnosis of thymoma for the
      mediastinal mass and pulmonary cryptococcosis for the cavitary lesion. Although
      ATL cells were not found in the peripheral blood, anti-HTLV-1 antibody was found
      to be positive. Natural killer cell activity was lower than normal control and
      other tests of humoral and cell-mediated immunity were normal. Histological
      examination of the specimens obtained from the thymoma revealed lymphocytic
      predominance without atypical cells such as ATL cells, but with integration of
      HTLV-1 proviral DNA. There seemed to be a causal relationship between HTLV-1
      carrier state and thymoma. Since there are no reported cases of HTLV-1 carrier
      associated with pulmonary cryptococcosis and thymoma, we report the first case
      with a review of the literature.

PMID- 7807759
TI  - [A case of diffuse alveolar hemorrhage accompanied by mesangial proliferative
      glomerulonephritis with positive perinuclear anti-neutrophil cytoplasmic
      antibody].
AB  - A 62-year-old man was admitted to our hospital because of low-grade fever and
      hemoptysis. Chest roentgenogram revealed diffuse infiltrative shadows with air
      bronchograms. Bronchoalveolar lavage fluid demonstrated bloody fluid, including
      many hemosiderin-laden macrophages. In addition, his laboratory data on admission
      revealed elevation of serum creatinine and BUN, and proteinuria and hematuria on
      urinalysis. Renal needle biopsy showed atrophic glomeruli and mesangial
      proliferative glomerulonephritis without crescent formation. A history of
      wheezing and slight eosinophila was also present, and we therefore suspected
      allergic granulomatous angitis. We performed airway sensitivity and reversibility
      tests, which were positive, and so we judged that he had an asthmatic component.
      Perinuclear antineutrophil cytoplasmic antibody (P-ANCA) was positive (x 1000)
      with ELISA. We diagnosed diffuse alveolar hemorrhage with mesangial proliferative
      glomerulonephritis and bronchial asthma. His general condition improved with oral
      administration of corticosteroid (50 mg/day) and immunosuppressive agent
      (cyclophosphamide; 50 mg/day), and his major symptoms disappeared within a few
      days.

PMID- 7807760
TI  - [A case of subperitoneal tuberculosis revealed by abdominal pain during pulmonary
      tuberculosis treatments].
AB  - The case was a 58 year-old female. During hospitalization for the treatment of
      pulmonary tuberculosis, she complained of pain in the left hypochondriac region.
      Abdominal CT revealed a mass between the abdominal wall and left lobe of the
      liver. Metastatic liver carcinoma was suspected by aspiration cytology, but no
      primary tumor could be identified. Therefore, an exploratory laparotomy was done,
      and the mass proved to be a subperitoneal tuberculoma. Tuberculous lymphadenitis
      was also found in lymph nodes of the upper abdominal cavity. Tuberculosis in the
      abdominal cavity has been rare in recent times in Japan. Therefore, this case
      provides valuable experience in the differential diagnosis of an abdominal mass.

PMID- 7807761
TI  - [A case of liver cirrhosis presenting with right pleural fluid without ascites].
AB  - A 80-year-old man was admitted to our hospital complaining of appetite loss, dry
      cough, and dyspnea on exertion. Chest X-ray film showed massive right pleural
      effusion. On physical examination, the right thorax was dull to percussion, and
      breath sounds of the right lung field were diminished. Examination of the
      cardiovascular system was unremarkable. Hepatosplenomegaly and ascites were not
      evident. The character of the pleural fluid was transudative. Cytological
      findings were negative and culture of the pleural fluid was normal. First, the
      pleural fluid was diminished by thoracic drainage. But, after the cessation of
      drainage, the pleural fluid soon reaccumulated. Abdominal ultrasonography showed
      typical liver cirrhosis pattern without ascites. An intraperitoneal injection of
      99mTc-sulfur colloid was followed by positive uptake of radioactivity in the
      right pleural cavity from 1 hour after the injection, demonstrating the existence
      of a direct perito-pleural communication. Thus, the diagnosis of liver cirrhosis
      presenting with right pleural fluid, without ascites was made. This case
      indicates that the absence of ascites cannot exclude cirrhosis as the etiologic
      cause of pleural effusion.

PMID- 7807762
TI  - [A case of respiratory bronchiolitis-associated interstitial lung disease].
AB  - We report the first case of respiratory bronchiolitis-associated interstitial
      lung disease in Japan. A 48-year-old man with a 36-pack-year smoking history was
      referred because of 6 months of dry cough. Chest X-ray showed bilateral
      reticulonodular shadows. HRCT scan showed bilateral reticulonodular and ground
      glass shadows with centrilobular distribution. BAL yielded 85 x 10(6) cells with
      99.5% macrophages. Histologic examination of the biopsy specimen obtained under
      thoracoscopy showed evidence of respiratory bronchiolitis, with accumulation of
      pigmented macrophages within respiratory bronchioles and adjacent air spaces
      associated with mild thickening of the peribronchiolar interstitium.

PMID- 7807763
TI  - [A case of multifocal eosinophilic granuloma presenting as a rib tumor].
AB  - A 19-year-old man was hospitalized because of left chest pain. He had a tumor in
      the left fifth rib with tenderness. Partial resection of the fifth rib was
      performed. Pathological examination showed granuloma with infiltration of
      histiocyte-like cells and eosinophils, and S-100 staining was positive.
      Therefore, the rib tumor was diagnosed as eosinophilic granuloma. Thereafter, the
      patient had recurrent bone lesions of the mandible, temporal bone, zygomatic
      bone, scapula, right eleventh rib, and tibia. Radiation therapy was effective for
      local treatment of each bone lesion. Moreover, pulmonary lesion was suspected on
      roentgenographic study. However, he had no respiratory symptoms and there was no
      significant change on roentgenographic findings over six years. It was considered
      that follow up for detection of bone and pulmonary lesions should be continued in
      this case.

PMID- 7807764
TI  - [A suspected case of T0N1M0 small cell carcinoma of the lung].
AB  - A 51-year-old man was admitted to our hospital with a chief complaint of cough.
      His chest X-ray and CT scan revealed enlargement of a left hilar lymph node.
      However, no primary lesion was apparent in the rest of the lung.
      Bronchofiberscopic findings were essentially normal. At surgery the mass was
      determined to be an enlarged lymph node (No. 11). No apparent malignant lesion
      was identified in the lung. Postoperative pathological examination showed small
      cell carcinoma in a part of the No. 11 lymph node. Despite a thorough systemic
      examination, no primary foci were detected. We have been following up this
      patient with chemotherapy for the approximately 2 year period since the
      operation, but no primary lesions have been detected as yet. Therefore, we
      speculate that this patient is a very rare case of primary unknown T0N1M0 lung
      cancer.

PMID- 7807765
TI  - [A case of primary pulmonary cryptococcosis showing infiltrative shadows in the
      unilateral lung field].
AB  - A case of primary pulmonary cryptococcosis is reported. A 76-year-old man,
      without underlying disease or immunological abnormalities, was admitted to the
      hospital. Chest X-ray revealed diffuse infiltrative shadows considered at first
      to be community-acquired pneumonia. A diagnosis of pulmonary cryptococcosis was
      performed using fluconazole, miconazole and transbronchial inhalation of
      amphotericin B. Cryptococcal antigen detection was performed by two latex
      agglutination methods: Crypto-test and Sero-direct test (Eiken-test). Comparing
      the results of the two tests, sensitivity was superior with the Sero-direct test,
      but the correlation between the titers of the two tests was good.

PMID- 7807766
TI  - [Prognostic factors influencing the growth of renal calculi].
AB  - Factors influencing the growth of renal calculi were examined. In order to
      calculate the volume of stone on X-ray film, stones obtained from open operation
      or spontaneous passage were measured long (a) and short (b) diameter, and
      equation to obtain stone volume was assumed. Stone volume = 0.43 (pi ab (a +
      b))/12 + 0.04 was the mostly related to the volume measured by water volume, when
      size was less than 2 cm in diameter. Using the equation, factors influencing the
      growth of renal calculi of 136 kidney, which were followed over 6 months, were
      studied with monovariate analysis. Of the 136 kidneys, 36 have calcium oxalete
      stones, 54 have mixed stones with calcium oxalate and calcium phosphate, 3 have
      mixed stones with calcium oxalate and uric acid, and other 43 have stones with
      unknown composition. Uric acid stones, cystine stones and infectious stones were
      excluded in the study. Growth of stone was greater in male than in female. Pelvic
      stones grew rapidly than renal caliceal stones. The patients were divided into
      two groups by growth rate; non growing (< 10%/year), and growing group (>
      10%/year), respectively. Excretion of urinary calcium was high in the growing
      group. Urinary magnesium/calcium was low in the growing group. When divided into
      two groups by growth volume; non growing (< 0.005 cm3/year), and growing group (>
      0.005 cm3/year), respectively, excretion of urinary calcium was high in the
      growing group and urinary magnesium/calcium was low in the growing
      group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7807767
TI  - [Long-term results of endourological treatment of urinary calculi: multivariate
      analyses of the risk factors related to recurrence or re-growth].
AB  - To evaluate the risk factors related to the long-term outcome of endourologic
      treatment of urinary calculi, data from the rates of recurrence or re-growth in
      145 patients with 167 renal units who were observed for more than 3 months at the
      Hiroshima University Hospital, were reviewed. The factors included in the present
      analysis were age, previous stone, location, number, size and composition of
      stone and procedures of treatment. Of 167 renal units, the overall recurrence and
      re-growth rates were 17% and 10%, respectively. The earliest recurrence and re
      growth appeared at 3 months after the treatment, and 71% of recurrence and 81% of
      re-growth occurred within 2 years. In 9 out of 20 renal units (45%) with
      unsuccessful treatment, residual stones enlarged during the follow-up. Stone
      located in renal calyx and pelvis, previous stone, multiple stones, size of stone
      more than 20 mm, stone composed of calcium oxalate and/or calcium phosphate and
      struvite stone were likely to be risk factors. However, on the univariate
      analysis there were no significance of difference among these variables. On the
      results of analysis by Cox's proportional hazards model, characteristics such as
      stone located in renal calyx and pelvis, size of stone more than 20 mm (p <
      0.01), treatment with percutaneous nephrolithotripsy (PNL), previous stone, size
      of stone between 10 mm and 20 mm, and multiple stones (p < 0.05), were
      significantly related to either recurrence or re-growth of stone.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7807768
TI  - [Treatment of advanced prostatic cancer--chronological change between 1975 and
      1991].
AB  - A chronological analysis of the clinical features and treatments of advanced
      prostatic cancer, stages C and D, was performed in 154 cases treated from 1976
      through 1991. These cases were divided into two chronological groups: 61 cases
      treated between 1976 and 1983, and 93 cases between 1984 and 1991. Concerning
      demographic features and diagnosis, the number of patients with lymph node
      metastasis was higher in the latter group. There was also increase in cases who
      were urologically asymptomatic and detected by checkup digital rectal examination
      or by the elevation of serum prostatic tumor markers. Histopathological
      differentiation was consistent between the two groups; more than 70% of cancers
      were moderately and poorly differentiated adenocarcinoma. As for the treatment,
      total prostatectomy was performed in eight cases in the latter against none in
      the earlier, but hormonal therapy remained the main treatment throughout the
      periods: 74.2% in the earlier and 70.7% in the latter. However the methods of the
      therapy have clearly changed; estrogens and castration were used less often in
      the latter period, while LH-RH analogues and antiandrogens replaced them although
      the therapy was equally effective in 82.3% of the cases in the earlier and in
      90.4% in the later period and five-year survival rate and the progression-free
      survival rate at three years showed no significant difference between the two
      periods. These results showed 1) refined quality of diagnosis 2) a change in mode
      of hormonal therapy and 3) no detectable improvement of survival in these 16
      years. Development of more effective therapies would be warranted for a better
      survival.

PMID- 7807769
TI  - [Experience of ileal neobladder for bladder cancer by Hautmann procedure].
AB  - Operative results of ileal neobladder by the Hautmann procedure were studied in
      the patients with bladder cancer. From 1990 to 1993, 23 patients underwent total
      cystoprostatectomy for transitional cell carcinomas of the bladder. In 12 of
      these patients, an ileal neobladder was constructed for total bladder replacement
      under the following criteria; patients 1) with cancer confined in the bladder
      (T3b, M0, N0 or less), 20 without carcinoma in situ extending to more than half
      of urothelium of the bladder, 3) without cancerous lesion in the bladder neck or
      the prostatic urethra, 4) with performance status of 0 and the age of 75 or less.
      Pathologically, the disease was grade 2 in 3 patients, grade 3 in 9, stage pT1b
      in 3, stage pT2 in 4, stage pT3a in 1 and stage pT3b in 4. Two of 3 patients with
      the disease of stage pT1b had multiple papillary tumors. The remaining one
      patient had microinvasive cancer that carcinoma in situ infiltrated into
      submucosal area. Radical cystoprostatectomy and total bladder replacement by
      Hautmann procedure was performed in all patients. The maximum neobladder capacity
      was 349.5 +/- 58.1 ml (mean +/- SD). The intravesical pressure at maximum
      capacity was 30.6 +/- 6.2 cmH2O. At half maximum capacity, the intravesical
      pressure was 17.1 +/- 6.8 cmH2O. the maximum urethral closure pressure and the
      functional urethral length were 89.2 +/- 38.1 cmH2O and 25.5 +/- 7.0 mm,
      respectively. One patient had stress urinary incontinence. Slight nocturnal
      incontinence was found in 2 patients and nocturia was 1.86 +/- 0.55
      times.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7807770
TI  - [Changes of plasma endothelin level in the early post-renal transplantation
      period].
AB  - Endothelin (ET) has been suggested to be involved in acute graft rejection of
      kidney transplantation and cyclosporin A (CsA) nephrotoxicity. For clarification
      of the pathophysiological role of ET in the early post-transplantation period,
      plasma endothelin-1 (ET-1) was measured by specific radioimmunoassay in renal
      transplant recipients, patients on maintenance hemodialysis (HD) and healthy
      volunteers. Twelve transplant recipients were used in this study, 8 of whom were
      living related subjects and 4 cadaver. Plasma ET-1 and graft function were
      measured each day, from 1 day prior and 7 days following transplantation and
      every week up to 5 weeks postoperatively. Plasma ET was measured in 20 other
      transplant recipients with stable function (serum creatinine < or = 1.8 mg/dl),
      20 maintenance HD patients with no residual renal function and 6 healthy
      volunteers. Mean plasma ET-1 was 13.0 +/- 4.5 pg/ml in 20 recipients with stable
      graft function, 21.7 +/- 6.5 in 20 HD patients and 1.5 +/- 0.4 in healthy
      volunteers. These differences are statistically significant (p < 0.02). Plasma ET
      1 showed significant decrease from 21.8 +/- 7.2 pg/ml prior to transplantation to
      12.8 +/- 4.0 when urinary output reached more than 1000 ml in living and
      cadaveric transplantation subjects. All three acute vascular rejections clearly
      indicated histologically increased plasma ET-1 accompanied by an increase in
      serum creatinine. A significant positive liner correlation was noted between
      plasma ET-1 and serum creatinine during the first week following living
      transplantation. Two patients with clinically and histologically suspected CsA
      nephrotoxicity showed transient increase in plasma ET-1.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7807771
TI  - [Clinical results of percutaneous pyeloplasty for ureteropelvic junction
      obstruction: 5 years follow-up].
AB  - We performed percutaneous endopyeloplasty on 20 patients between February, 1988
      and July, 1993. Eighteen patients had primary and two had secondary ureteropelvic
      junction (UPJ) obstructions. There were 15 female and 5 male patients, whose ages
      ranged from 14 to 77, with an average of 43.6. The length of the follow-up after
      pyeloplasty ranged from 4 to 69 months with an average of 28.7 months. Among the
      20 patients, there were 4 high insertion type cases, a bifid renal pelvis in one
      case and one case combined with a renal stone. Incisions were made with a hook
      shaped cold knife and Ono's transpelvic extraureteral approach was used in most
      patients. Catheters were placed at the upper and the lower of renal pelvis in the
      patient with a bifid renal pelvis. In the case with a renal stone, pyeloplasty
      was successively performed after percutaneous nephrolithotomy in a single
      session. An endopyelotomy stent (14 Fr) was indwelled for 6 weeks in all patients
      except one. All patients had a low grade fever and abdominal pain for a few days
      after their operations, but there were no major complications. In nineteen
      patients (95%), the symptoms improved and their obstructive patterns disappeared
      or improved during follow-up. Complete ureteral stricture was found in one case
      at the removal of the stent and open pyeloplasty was performed. Percutaneous
      endopyeloplasty is a safe and useful technique, but further evaluation and/or
      better techniques are needed for avoiding recurrence of obstruction.

PMID- 7807772
TI  - [Development of spinal bone metastasis by MBT-2 tumor in mice].
AB  - The biology of skeletal metastasis is poorly understood. In order to establish an
      animal model of spinal bone metastasis, we injected MBT-2 tumor cells into the
      tail vein of C3H/He mice while the inferior vena cava was occluded. By this
      technique, the tumor cells were transferred into the vertebral plexus. Spinal
      lesions developed in 12 of 15 (80%) experimental mice and in none of the control
      mice. All bone lesions resulted in local bone destruction. The predominant site
      of bone metastasis was lumbarvertebrae; other affected sites were thrpelvis and
      coccyges. This model should be of value in understanding the pathogenesis of
      spinal bone metastasis and in studying the effects of various agents on the
      prevention and control of spinal lesions.

PMID- 7807773
TI  - [Production of a lymphocyte chemotactic factor by human renal cancer cells].
AB  - Tumor infiltrating lymphocyte (TIL) is commonly observed in renal cell carcinoma
      (RCC) tissues. First step of lymphocyte accumulation in cancerous tissues is the
      lymphocyte migration toward cancer cells. However, no conclusion has been drawn
      which cytokine is involved in TIL of RCC. The purpose of this study is the
      identification of a lymphocyte chemotactic factor (chemokine) produced by a newly
      established RCC cell line. A new human renal cancer cell line (TC-2) was
      established from a primary site of a 52-year-old man. A marked lymphocyte
      infiltration was noticed at the cancer tissue. A tissue culture has been
      continued for 24 months. Flow cytometric analysis of this cell line revealed DNA
      aneuploidy. A human karyotype, with a modal number of 72, and consistent
      abnormalities, such as 4q+ and 5q-, were demonstrated by Giemsa banding analysis.
      Approximately 2.9 fold of lymphocyte chemotactic activity was detected in the
      culture supernatant of TC-2 cells (TC-2CM) as measured by in vitro migration
      assay. Sixty percent of this activity was abrogated by adding the neutralizing
      antibody against interleukin-8 (IL-8) into TC-2CM. Analysis of surface markers of
      migrating lymphocytes disclosed that lymphocytes expressing CD3, CD8 and CD16
      phenotype predominantly showed migration. These results suggested that
      chemotactic activity for lymphocytes derived from TC-2 cells was partly IL-8.

PMID- 7807774
TI  - [Results of one-stage hypospadias repair].
AB  - We reviewed 17 patients who had first undergone one-stage hypospadias repair.
      According to the criteria proposed by Keating and Duckett, the operative
      procedure performed was the MAGPI procedure in 2 patients, the pyramid procedure
      in 2, the Mathieu procedure in 1, the onlay island flap procedure in 6, the
      transverse preputial island flap and glans channel procedure (Duckett) in 4 and a
      combined method using the buccal and bladder mucosa graft in 2. The age of the
      patients ranged from 11 months to 22 years (median age 3.2 years). Postoperative
      follow-up ranged from 3 to 30 months (mean 7 months). Postoperative complications
      requiring revision occurred in 4 patients; urethrocutaneous fistula developed in
      1 patient with the onlay island flap, urethral sticuture at the anastomosis and
      meatus in 1 patient with the transverse preputial island flap, meatal retraction
      in 1 patient with the mucosal graft, and urethral stricture at the distal
      anastomosis and bladder stone in the other patient with the mucosal graft. These
      complications were successfully revised by simple operations. Ventral skin
      tethering caused by scar contracture developed in 2 patients with the preputial
      island flap, and spontaneously improved with time in 1 patient. These results
      indicate that the criteria proposed by Keating and Duckett is proper to select an
      operative procedure for hypospadias.

PMID- 7807775
TI  - [Prognostic factors in patients with stage 4B renal cell carcinoma following
      nephrectomy].
AB  - We studied on prognostic factors in 106 patients with stage 4B renal cell
      carcinoma having distant metastases at the diagnosis. In this study, we excluded
      patients who died after nephrectomy within 30 days and those who died without
      cancer. As the result, significant differences were observed upon the 8 factors
      in those patients as summarized bellow: 1) The histological malignancy (grade):
      there observed an improved survival in patients with grade II compared to those
      with grade III and IV. 2) The opportunity of diagnosis: we classified the
      patients into 4 types: patients with urinary symptoms, those with non-urinary
      symptoms, those with metastatic symptoms and those with tumours found
      incidentally. There observed an improved survival in patients with tumours found
      incidentally compared to those with urinary symptoms and non-urinary symptoms. 3)
      The number of 5 laboratory findings such as anaemia, positive reaction of C
      reactive protein (CRP), elevation of erythrocyte sedimentation rate (ESR),
      elevation of alpha 2-globulin and immunosuppressive acidic protein (IAP): there
      observed an improved survival in patients with less than 2 abnormal laboratory
      findings compared to those with more than 3. 4) The regional lymph node
      metastasis: there observed an improved survival in patients without lymph node
      metastasis compared to those with lymph node metastasis. 5) The number of
      metastatic organ: there observed an improved survival in patients with one organ
      metastasis compared to those with more than two. 6) The treatment modality: there
      observed an improved survival in patients receiving interferon (IFN) therapy/IFN
      plus chemotherapy than those receiving chemotherapy alone.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7807776
TI  - [End stage polycystic kidney disease: the study for upper urinary tract infection
      & hemorrhage into the cysts].
AB  - The results have been reviewed of 41 patients with end stage polycystic kidney
      disease on maintenance hemodialysis. The patients ranged in age from 34 to 83
      years with an average age of 55 years and 25 patients were male, 16 were female.
      The duration of maintenance hemodialysis in the patients was from 1 to 200 months
      with an average time of 69 months. Infection of the cysts and pyelonephitis
      occurred 22 times in 13 patients (32%) and hemorrhage into the cysts occurred 15
      times in 13 patients (32%). To control the infection, bilateral nephrectomy was
      required in 10 patients and 1 patient was undergone unilateral nephrectomy. Of 13
      patients with the hemorrhagic cysts, 5 were undergone bilateral nephrectomy and 2
      were undergone unilateral nephrectomy. Six patients died during follow up and the
      cause of death were 1) cardiac failure, 2) cerebral hemorrhage, 3) cardiac
      infarction, 4) pneumonia after nephrectomy, 5) massive bleeding after second
      operation for adhesive ileus due to first nephrectomy, 6) unknown. Fourteen
      patients but one undergone bilateral nephrectomy were followed for an average
      time of 70 months after nephrectomy. Such as complication due to bilateral
      nephrectomy, anemia occurred in 13 patients (93%) and hypotension occurred in 5
      patients (33%). Bilateral nephrectomy was effective procedure in safety for end
      stage polycystic kidney patients with the infection and the hemorrhagic cysts
      because anemia and hypotension which occurred usually after bilateral nephrectomy
      now can be controlled goodly.

PMID- 7807777
TI  - [A familial case of prostate cancer in three brothers].
AB  - We treated three brothers for prostate cancer. The first brother developed the
      disease of poorly differentiated adenocarcinoma at the age of 76, and was treated
      with endocrine therapy but died of recurrent cancer at age 80. The second brother
      was diagnosed poorly differentiated adenocarcinoma at age 75, and he is alive at
      age 80 without recurrence after endocrine therapy. The third brother developed
      moderately differentiated adenocarcinoma at age 58, and was treated with
      endocrine therapy but died of recurrent cancer at age 73. We have seen few
      familial cases of prostate cancer. The first such case is reported here in Japan.
      Eleven similar cases of familial prostate cancer involving three or more brothers
      have been reported in the Western literature.

PMID- 7807778
TI  - [Transitional cell carcinoma of bladder occurring during pregnancy: report of two
      patients].
AB  - Primary transitional cell carcinoma (TCC) of the bladder occurring during
      pregnancy is extremely rare and only 16 patients have been reported in the
      literature. Patient 1: A 24-year-old primigravida at 33 weeks of gestation
      presented with gross hematuria. Cystoscopy revealed a large bladder tumor. After
      delivery TUR-Bt was performed. Because of frequent reccurrences after TUR-Bt,
      radical cystectomy was done. Pathological study revealed transitional cell
      carcinoma, G1-G2, pTa. Patient 2: A 34-year-old gravida 11 at 6 weeks of
      gestation presented with gross hematuria. Cystoscopy revealed a papillary bladder
      tumor. TUR-Bt was performed after artificial abortion. Pathological study
      revealed papillary transitional cell carcinoma, G1 > G2, pTa. Eighteen patients
      of TCC of the bladder occurring during pregnancy were reviewed. Fifteen of the 18
      patients presented with gross hematuria. All patients had superficial, solitary,
      grade 1 or 2 papillary TCC, except one grade 3 patient. Cystoscopy should be
      considered in all pregnant women with gross hematuria. Small TCCs of the bladder
      during pregnancy can be treated safely by TUR-Bt during pregnancy or after
      delivery.

PMID- 7807779
TI  - [Inferior vena caval tumor thrombus in a patient with renal angiomyolipoma
      associated with tuberous sclerosis].
AB  - A 34-year-old woman with tuberous sclerosis presented with an increase of an
      abdominal mass and intermittent left flank pain on May 20, 1991. Computed
      tomography showed multiple bilateral renal masses with fatty density areas and a
      fatty density thrombus in the inferior vena cava, which extended through the
      right renal vein of the right kidney on ultrasonography. The inferior vena caval
      thrombus was also demonstrated by magnetic resonance imaging. Since marked
      deterioration of the right renal function was found on renography, right radical
      nephrectomy with thrombectomy was performed on July 2. Microscopically all tumors
      were identical with angiomyolipoma. She was discharged on Jury 20 and had been
      followed with good renal function at the outpatient clinic for more than 2 years.
      Follow up CT revealed no interval changes in the left renal masses.

PMID- 7807780
TI  - Recognition of scuba diving accidents and the importance of oxygen first aid.

PMID- 7807781
TI  - Standing orders for trauma care.

PMID- 7807782
TI  - One emergency department's system for improved pediatric codes.

PMID- 7807783
TI  - Advice for dealing with job loss.

PMID- 7807784
TI  - Recognition and treatment of pediculosis (head lice) in the emergency department.

PMID- 7807785
TI  - Pharmacologic management of hypertensive crisis in the emergency department.

PMID- 7807786
TI  - Emergency nursing assessment and notes.

PMID- 7807787
TI  - Emergency department programs for patients with chest pain.
AB  - The development and implementation of specialized ED programs for patients with
      chest pain are continually evolving, although the initial goals of "chest pain
      centers" may vary dramatically. ED nursing staff play an important role in the
      delivery of rapid cardiac care and support of community education programs, both
      of which are intended to decrease the time between recognition of clinically
      significant chest pain and initiation of appropriate interventions.

PMID- 7807788
TI  - Computers: getting started.
AB  - Because there is not much written about computer application in the emergency
      department you will frequently find yourself reading about applications in other
      areas. It is up to you to apply this information in the emergency setting. This
      makes you pioneers, in search of a new and better tomorrow. Our future is not yet
      written. It is waiting on you and your creative ideas to keep the wagon rolling.
      Don't let the new territory of informatics, hardware hardships, and foreign
      computer languages get you down. Accept informatics as just another challenge,
      like the many we have faced successfully in the past. Use these resources and
      your expertise in emergency nursing to create innovative informatic systems.

PMID- 7807789
TI  - Erroneous reporting of sexually transmitted diseases.

PMID- 7807790
TI  - Program planning.

PMID- 7807791
TI  - Why adult patients come to a pediatric emergency department: a retrospective
      review at one childrens hospital.

PMID- 7807792
TI  - Trauma center challenge: survival in a managed care market.

PMID- 7807793
TI  - A 4-year-old with petechial rash.

PMID- 7807794
TI  - P.A.R.T.Y. on, Alberta!

PMID- 7807795
TI  - Canadian update: the "a-nurse-is-a-nurse" trend in Canada.

PMID- 7807796
TI  - An Easter blessing: one emergency nurse's story.

PMID- 7807797
TI  - Emergency Nurses Association position statement. Spontaneous abortions in the
      emergency department.

PMID- 7807799
TI  - Be alert for medical information cards.

PMID- 7807798
TI  - President's message: here today, gone tomorrow.

PMID- 7807800
TI  - More on family presence during resuscitation.

PMID- 7807801
TI  - More on sedating children.

PMID- 7807802
TI  - Rape or self-injury?

PMID- 7807803
TI  - Accidental defibrillation of the cranium.
AB  - The potential dangers of electricity and its use in the clinical setting are
      obvious. When clinical equipment is taken out of the clinical setting, machine
      malfunction or unexpected function in the hands of untrained and unskilled
      individuals can yield disasterous results. The benefits of community education
      must be weighed carefully in light of the potential danger.

PMID- 7807804
TI  - The new ACLS tachycardia algorithm: flexible guidelines for an old problem.
AB  - Most nurses will find that the tachycardia algorithm gives guidance in treatment
      but flexibility to allow for patient variables. Although it may at first appear
      complex, the decision tree carries no surprises. Treatments are similar to those
      already seen in emergency cardiac care. Remember, the algorithms are offered as a
      guide, and individual physicians' treatment decisions may vary.

PMID- 7807806
TI  - [Waka and haiku on children].

PMID- 7807805
TI  - [Visiting nursing service: our clients are patients discharged from large
      hospitals and highly dependent].

PMID- 7807807
TI  - [Status of nursing personnel as professionals--as defined in the related laws].

PMID- 7807808
TI  - [Review of current health care system: position of nursing personnel in health
      care teams].

PMID- 7807809
TI  - [We admire nurses: activity of Consumer Organization for Medicine & Law (COMPL)
      and my experience at the Beth Israel Hospital in Boston].

PMID- 7807811
TI  - [Telephone counseling: problems and their solutions].

PMID- 7807810
TI  - [The nursing shortage and the 1990's: realities and remedies].

PMID- 7807812
TI  - [Symposium on health care problems and issues in developed countries--Europe].

PMID- 7807813
TI  - [Cost reduction effort by nurses in hospital].

PMID- 7807814
TI  - [Risk management in health service].

PMID- 7807815
TI  - [Survey of employment of nurses with academic degrees].

PMID- 7807816
TI  - [Mental health counseling service by nursing personnel on National Nursing Day].

PMID- 7807817
TI  - [Government subsidy to local governments to increase public health nurses].

PMID- 7807818
TI  - [Personnel evaluation to encourage and motivate staff. Staff evaluation helps
      setting individual goals].

PMID- 7807820
TI  - [Personnel evaluation to encourage and motivate staff. Peer review--exchange of
      notes on points of excellence].

PMID- 7807819
TI  - [Personnel evaluation to encourage and motivate staff. Management and staff-
      interactive communication].

PMID- 7807821
TI  - [Personnel evaluation to encourage and motivate staff. Patient satisfaction
      expressed in their notes].

PMID- 7807822
TI  - [Personnel evaluation to encourage and motivate staff. Relative evaluation vs.
      absolute evaluation].

PMID- 7807823
TI  - [Workshop on bone marrow transplant: marrow donor programs in other countries].

PMID- 7807824
TI  - [National nursing policy--the health center law to be amended to the community
      health law].

PMID- 7807825
TI  - [Books on old age: lonely old age].

PMID- 7807826
TI  - [Report by director nursing: nursing shortage].

PMID- 7807827
TI  - [The 1994 national nursing budget].

PMID- 7807828
TI  - [Report by director of nursing: fresh nurse orientation].

PMID- 7807829
TI  - [We admire nurses: activity of Consumer Organization for Medicine & Law (COML)
      and our clients].

PMID- 7807831
TI  - [The 1994 revision of medical treatment fees].

PMID- 7807830
TI  - [Human gene therapy].

PMID- 7807832
TI  - [Bone marrow transplantation: complications when drawing bone marrow from donor].

PMID- 7807833
TI  - [Symposium on health care issues and problems in developed countries: United
      States].

PMID- 7807835
TI  - [Acceptance of disability and informed counsel].

PMID- 7807834
TI  - [Survey of patients discharged after receiving operation for pulmonary cancer].

PMID- 7807836
TI  - [Nurses' voices have been heard in formulating the 1994 budget].

PMID- 7807837
TI  - [Fresh nurse orientation and training. Preparing nurses to provide specialized
      hospital care].

PMID- 7807838
TI  - [Fresh nurse orientation and training. Education needed to care for very sick
      patients].

PMID- 7807839
TI  - [Fresh nurse orientation and training. Introduction of preceptorship for fresh
      nurse training].

PMID- 7807841
TI  - [Fresh nurse orientation and training. Training I received as a fresh nurse].

PMID- 7807842
TI  - [The nursing shortage and the 1990s: realities and remedies. 1].

PMID- 7807840
TI  - [Fresh nurse orientation and training. Messages from senior nurses to fresh
      nurses].

PMID- 7807844
TI  - [Nursing worldwide].

PMID- 7807843
TI  - [Review of current health care system: primary care and role of nurse
      practitioner].

PMID- 7807845
TI  - [National nursing policy. Provision of correspondence course for assistant nurses
      to become nurses].

PMID- 7807846
TI  - [Report of director of nursing--status of female workers and the nursing
      profession].

PMID- 7807847
TI  - [We admire nurses: patients rely on nurses on "informed consent"].

PMID- 7807848
TI  - [Cobwebbed patients in emergency room].

PMID- 7807849
TI  - [Information from WHO/PHC Nursing Collaborative Center, Tokyo].

PMID- 7807850
TI  - [Human gene therapy--prospects of gene as a drug].

PMID- 7807852
TI  - [The nursing and the 1990s: realities and remedies--hospital nursing shortage.
      2].

PMID- 7807851
TI  - [Visiting nursing service--the more we work, the heavier our deficit becomes: the
      balance after one year's operation of the station].

PMID- 7807853
TI  - [Assistance to help independence of patients].

PMID- 7807854
TI  - [The 1994 white paper on women "Status of Women Today: Changing Family Life and
      Life of Women". Interview by A. Kawaguchi].

PMID- 7807855
TI  - [Health institution for the elderly--quality of service and characteristics of
      residents].

PMID- 7807858
TI  - [The gist and problems of the 1994 Revision of Medical Treatment Reimbursement
      System--what nursing personnel should know. Quality assurance of nursing service
      under the Revised Reimbursement System].

PMID- 7807857
TI  - [Proposed scope of practice of a new health professional "clinical psychiatric
      technologist" to be licensed by the government].

PMID- 7807856
TI  - [Nutrition control of cancer patients under chemotherapy].

PMID- 7807859
TI  - [The gist and problems of the 1994 Revision of Medical Treatment Reimbursement
      System--what nursing personnel should know. How nursing services are affected by
      the recent revision of the medical reimbursement system].

PMID- 7807860
TI  - [The gist and problems of the 1994 Revision of Medical Treatment Reimbursement
      System--what nursing personnel should know. How does the new system improve
      nursing service in quantity and in quality].

PMID- 7807861
TI  - [The gist and problems of the 1994 Revision of Medical Treatment Reimbursement
      System--what nursing personnel should know. Visiting nursing service still held
      financially unstable].

PMID- 7807862
TI  - [The gist and problems of the 1994 Revision of Medical Treatment Reimbursement
      System--what nursing personnel should know. How patient care in psychiatric
      hospitals would be affected].

PMID- 7807863
TI  - [The gist and problems of the 1994 Revision of Medical Treatment Reimbursement
      System--what nursing personnel should know. The new system dows not pay for
      carers' fees].

PMID- 7807864
TI  - [Report of director of nursing--merits of locating in a rural area].

PMID- 7807865
TI  - [We admire nurses: patients' class to become wise patients].

PMID- 7807866
TI  - [Physical distance between patients and physician].

PMID- 7807867
TI  - [Multimedia and nursing].

PMID- 7807868
TI  - [Development of independent practicing nurses--how I started independent
      practice].

PMID- 7807869
TI  - [Bone marrow transplantation: complications of organ recipients].

PMID- 7807870
TI  - [The nursing shortage and the 1990s: realities and remedies--measures implemented
      at "magnet hospital". 2].

PMID- 7807871
TI  - [Review of current health care system--working as a health care team].

PMID- 7807872
TI  - [Nurse-patient relationship is similar to trainer-wrestler relationship].

PMID- 7807873
TI  - [Seminar on infection control nursing at Royal College of Nursing].

PMID- 7807874
TI  - [Care of AIDS patients in the U.S].

PMID- 7807875
TI  - [A welcome proposal from a health care consumer to establish a foundation to
      accept public donation as an expression of gratitude for nurses for the care they
      received].

PMID- 7807876
TI  - [Improved hospital nursing service through review of routine procedures. Hospital
      infection control procedures].

PMID- 7807877
TI  - [Improved hospital nursing service through review of routine procedures. Taking
      morning temperature at 8:30 instead of 6.00].

PMID- 7807878
TI  - [Improved hospital nursing service through review of routine procedures.
      Communication with patients with tracheal tubes].

PMID- 7807879
TI  - [Improved hospital nursing service through review of routine procedures.
      Communication with physicians].

PMID- 7807880
TI  - [Improved hospital nursing service through review of routine procedures. Medical
      supplies inventory control].

PMID- 7807881
TI  - [Improved hospital nursing service through review of routine procedures. Hands
      disinfection by swab method and basin method].

PMID- 7807882
TI  - [Improved hospital nursing service through review of routine procedures. Better
      ways to clean patients' bedsheets].

PMID- 7807883
TI  - [Improved hospital nursing service through review of routine procedures.
      Medication methods].

PMID- 7807885
TI  - [JNA research and investigation reports--summing up].

PMID- 7807884
TI  - [Improved hospital nursing service through review of routine procedures. Primary
      nursing for diabetic patients].

PMID- 7807886
TI  - [Soft-tissue rhabdomyosarcoma of the lesser pelvis].
AB  - For the 1967-1989 period of time of 225 patients with malignant nonorganic small
      pelvis tumors in 15 the soft tissues rhabdomyosarcoma of small pelvis cavity was
      diagnosed (including 7 children and 8 adults). The main tumor symptoms are the
      pain and the disorders of physiologic excretions. The fourth stage of the disease
      was diagnosed in 13 of 15 patients. In spite of performance of extensive combined
      intervention, chemotherapy and irradiation therapy the treatment results are
      poor: the whole of the patients have died for a period of 3 years (mainly up to 1
      year period of time).

PMID- 7807887
TI  - [A combination of primary cancer and sarcoma of different sites].
AB  - The authors presents 9 observations of the cancer and sarcoma association, and
      the peculiarities of their appearance, clinical course and treatment. It was
      concluded that the therapeutical tactics must be differentiated, and the late
      follow-up results are quite similar to that obtained in the patients with
      solitary tumor.

PMID- 7807888
TI  - [The metastasis of cancer of the extrahepatic bile ducts].
AB  - The pathoanatomical investigations results in 105 patients with extrahepatic
      biliary ducts cancer are presented. The organotropism and the lymphotropic
      metastatic spreading predominance are revealed. The most frequently involved are
      the lymph nodes (73.6% observations), liver (52.8%), lesser omentum (20.7%),
      lungs (11.3%). The hematogenic spreading way for the cancer cells causes the
      distant metastases appearance in the lungs, spleen, ovaries, kidneys, adrenal
      glands. The implantation metastatic spreading way is quite uncommon.

PMID- 7807889
TI  - [The diagnosis of neurogenic neoplasms of the lesser pelvis].
AB  - For the 1967-1989 period of 330 patients with nonorganic small pelvis cavity
      tumors in 93 (28.3%) the neurogenic neoplasms were diagnosed, including 45
      nonmalignant and 48-malignant. At initial admission in 30.1% observations the
      diagnostical mistakes were committed due to low oncological watchfulness of
      general profile physicians and the finger rectal examination neglect. Clinical
      examination of the patients was the main source of information about neurogenic
      neoplasms. The use of special examination methods is obligatory for the tumor
      spreading detection.

PMID- 7807890
TI  - [The early withdrawal of antibiotics in the postoperative period as the cause of
      the occurrence of suppurative inflammatory complications in oncological
      proctology].
AB  - The problems of antibiotics use duration after operations on the colon are
      discussed in the article. The authors supposes the early antibiotics abolition
      inexpedient because of serious complications appearance possibility. Even during
      the noncomplicated postoperative course the optimal antibiotic therapy duration
      is 7-10 days long.

PMID- 7807891
TI  - [A surgical approach to the distal portion of the internal carotid artery before
      its entry into the cranial cavity].
AB  - The access to the distal part of internal carotid artery before her entrance to
      the skull cavity was depicted. His advantages are the minimal traumaticity,
      obligatory manoeuvre of artery taking out from beneath the laryngo-pharyngeal
      plexus for her complete exploration, the absence of postoperative swallowing and
      phonation disorders. The access was applied in 32 patients, including 6 in
      bilateral fashion (with 5-6 mos interoperative interval).

PMID- 7807892
TI  - [The use of continuous plasmapheresis and extracorporeal laser irradiation of the
      blood in treating diabetic angiopathies of the lower extremities].
AB  - The plasmapheresis (PP) with the help of the PP-05 apparatus was applied in the
      treatment of 70 patients with the low extremities diabetic angiopathy. The
      optimal plasma exfusion dose is from 600 to 1100 ml. Under the PP influence the
      blood glucose level reduced proportionally to the excreted plasma quantity, the
      rheovasographic index on the low extremities increased from 0.41 +/- 0.15 to 0.64
      +/- 0.6; the bloodflow velocity in the peripheral arteries of low extremities
      have got the 2.2-fold rise according to the dopplerography data. In comparison
      with a control group of patients the exarticulation conduction frequency
      decreased from 20 to 8, and extremities amputation--from 14 to 5.

PMID- 7807893
TI  - [The preoperative drug correction of disorders in myocardial functional reserve
      in patients with ischemic heart disease].
AB  - The optimally adjusted doses of phinoptin, cordarone and cordypin were applied as
      the preoperative preparation complex in 30 ischemic heart disease patients with
      the stress angina pectoris of the II-IV functional class. It promoted the total
      blood peripheral resistance decrease, pre- and postload lowering, the contractile
      myocardial function increase, the pain syndrome abolition, and permitted to
      prepare the patients effectively for the aortocoronary shunting operation.

PMID- 7807894
TI  - [The use of endolymphatic chemotherapy in patients with metastatic stomach
      cancer].
AB  - The results of the endolymphatic chemotherapy application in patients with
      metastatic cancer of stomach are presented. The low toxicity and high
      effectiveness were suggested. One-year survival was achieved in 42.2% of
      patients.

PMID- 7807895
TI  - [The surgical treatment of closed chest trauma with instability of the thoracic
      skeleton].
AB  - The results of treatment of 864 sufferers with closed thoracic trauma, including
      182 with the syndrome of traumatic instability of the chest are summarized. The
      role and place of severe injuries to the thoracic frame in the structure of a
      thoracic trauma were elucidated, terminology and typology of this type of trauma
      were defined more precisely, the effect of injury to the thoracic frame on the
      outcome of traumatic disease was studied.

PMID- 7807896
TI  - [Errors in establishing the blood group by the ABO system using hemagglutinating
      sera and monoclonal antibodies].
AB  - The authors have analyzed the blood group primary ascertainment results in 13,044
      examined persons with the help of hemagglutinating serums and in 6257--with the
      help of monoclonal antibodies. There were find out 198 (1.5%) and 137 (2.2%)
      mistakes accordingly, committed due to the infringement of blood group
      ascertainment procedure instructions.

PMID- 7807897
TI  - [Cleansing and drainage of the abdominal cavity in patients with a perforated
      pyloroduodenal ulcer and disseminated peritonitis].
AB  - The results of surgical treatment of 125 patients with perforative pyloroduodenal
      ulcer and wide-spread peritonitis were studied. Postoperative mortality was 3.2%.
      The method of cleansing and drainage of abdominal cavity was suggested, which
      allowed to avert the beginning of such severe complications as abscess and
      progressive peritonitis.

PMID- 7807898
TI  - [The recurrence of peptic ulcer after selective proximal vagotomy].
AB  - The treatment results of 245 patients with ulcer disease recurrence, 162 of whom
      the repeated operations were conducted, were analyzed. Most frequent recurrence
      cause is an incomplete vagotomy and other procedure faults. During the repeated
      operation performance the gastric resection is obligatory only owing to the
      impossibility of revagotomy conduction, or if the previously conducted vagotomy
      was undoubtedly complete.

PMID- 7807899
TI  - [The use of regional lymphotropic therapy in patients with acute complicated
      cholecystitis].
AB  - The results of the regional lymphotropic therapy application in 58 patients with
      an acute complicated cholecystitis are presented. The drop-infusion
      administration of the lymph outflow promoting drugs, antibiotics and antiseptics,
      proteases inhibitors and cytostatics, immunostimulants was conducted in the
      postoperative period. The result of the treatment is favourable.

PMID- 7807900
TI  - [The amino acid background of patients with obstructive jaundice before and after
      the surgical removal of the obstacle to bile outflow].
AB  - The amino acid pool of blood plasma, liver and bile was examined before and after
      operative elimination of biliary hypertension cause. The blood plasma
      concentration of the majority of free amino acids (especially the sulfur
      containing and big neutral) before operation at cholestasis is increased in
      comparison with donors. For the bile outflow normalization after operation the
      most informative is the content in liver, blood plasma and bile of taurine,
      glycine and the amino acids metabolically associated with them.

PMID- 7807901
TI  - [The prevention and treatment of adhesive and dynamic intestinal obstruction by
      nasointestinal splinting (intubation)].

PMID- 7807902
TI  - [The surgical treatment of inguinal hernia].
AB  - The results of operative treatment of 496 patients with inguinal hernia are
      presented. The incidence of development of a recurrence was 2.7-3.3%.

PMID- 7807903
TI  - [The effect of polysorb on the course of the wound process].
AB  - The peculiarities of a contact of the sorbent particles of a polysorb for medical
      purposes with the somatic cells have been studied. The destructive action of the
      preparation its capability to block the functionally active sites of a cellular
      membrane were revealed. The recommendations on clinical use of a polysorb have
      been developed.

PMID- 7807904
TI  - [The use of endolymphatic therapy in patients with a suppurative surgical
      infection].
AB  - The experience with the use of endolymphatic therapy (ET) in 110 patients with
      purulent surgical infection (50--with acute sepsis, 60--with localized infection
      against the background of diabetes mellitus) has been summarized. In acute
      sepsis, ET was the basis for the other methods of detoxication, the effect of its
      isolated use was a short-term one. In local purulent inflammation against the
      background of diabetes mellitus, the use of ET is highly effective, it can be
      used in the preoperative preparation of the patients with necrotic lesion of the
      lower extremities for improvement of the results of operative treatment.

PMID- 7807905
TI  - [The use of ozone for treating suppurative wounds].
AB  - Pathogenetic substantiation of the use of ozone for the treatment of purulent
      infection in surgery is given. A technique for the use of the method and its
      advantages as compared to antimicrobial remedies is described. A comparative
      assessment of the effectiveness of the suggested and existing methods was carried
      out.

PMID- 7807906
TI  - [The prognostic significance of natural killers and dehydrogenases of the
      peripheral blood lymphocytes in patients with a suppurative inflammation].
AB  - In patients with purulent inflammation foci of various location, reduction in the
      number of natural killers (NK) and in the activity of alpha
      glycerophosphatedehydrogenase (alpha-GPDH) and adenosinetriphosphatase (ATP-ase)
      of lymphocytes was revealed. Maximum reduction in indices of NK, alpha-GPDH and
      ATP-ase was noted in patients with diffuse peritonitis, phlegmonous-gangrenous
      cholecystitis, destructive appendicitis. After treatment, the mentioned indices
      increased, but by the time of discharge of the patients from the hospital they
      were lower than the normal ones.

PMID- 7807908
TI  - [The detoxifying action of peritoneal dialysis in experimental acute diffuse
      peritonitis].
AB  - The use of fatty substances (cod-liver oil and fatty emulsions) in association
      with streaming and dropping dialyzing solutions injection every 4 h have
      permitted to increase the peritoneal dialysis duration at the acute common
      peritonitis up to 5 days (the method was proposed by A. A. Shalimov and V. I.
      Shaposhnikov in 1970). The experiment done on 47 dogs have confirmed the
      peritoneal dialysis promotion of homeostasis indexes normalization due to the
      pronounced detoxication effect.

PMID- 7807907
TI  - [The efficacy of leukinferon in suppurative-septic diseases].
AB  - In the complex of treatment of purulent-septic diseases leukinferon at a dose of
      300 IU/kg was used according to the following scheme: 3 injections with the 48 h
      interval between injections. The effect of leukinferon mainly on the function of
      neutrophil granulocytes and subpopulation of T-lymphocytes was established.
      Together with clinico-laboratory data indicative of the effectiveness of
      treatment, normalization of interferon status and decrease in the level of a
      circulating factor of tumour necrosis in seriously ill patients was observed.

PMID- 7807909
TI  - [The immediate results of the combined treatment of rectal cancer using intra
      arterial selective polychemotherapy].
AB  - The treatment experience of 127 patients with the locally spread rectal cancer
      was summarized. The combined with preoperative intraarterial chemotherapy course
      application causes significant injurious effect on the tumor (more than 3 times
      decrease of the viable tumor tissue part by volume in rectal adenocarcinoma, the
      appearance of subcapsular necrosis regions in metastatically injured regional
      lymphatic nodes in 32.2% of observations) and is characterized by low common
      toxicity.

PMID- 7807910
TI  - [Dynamic changes in the healing of liver wounds while using the new hemostatic
      preparation kaprofer].
AB  - The liver wound healing dynamics under the influence of a new hemostatic
      preparation kaprofer was studied in experiment on 61 rabbit. During the
      histological investigation it was determined that while putting on the
      preparation on the wound the fibrinous clot of light brown colour is generated
      immediately; on the second day the wound surface has a light brown colour, fibrin
      patch at the centre; on the fourth day she has a whitish colour due to the
      cicatrix formation; on the eighth day the cicatrix is formed, and abundantly
      vascularized cicatricial and fibrillar tissue zones.

PMID- 7807912
TI  - [The expediency of a test exam in the clinical aspects of surgical diseases].

PMID- 7807911
TI  - [Current problems in the organization of surgical care for the rural population].

PMID- 7807913
TI  - [The legal bases of a surgical intervention].

PMID- 7807914
TI  - [The use of autovaccines prepared on a base of microbial synthesis products for
      the stimulation of body antitumor resistance].

PMID- 7807915
TI  - [Extravasal compression of the popliteal artery].

PMID- 7807916
TI  - [The importance of ultrasonic and morphological studies in the differential
      diagnosis of tumor, dyshormonal and inflammatory diseases of the breast].
AB  - The ultrasonic examination results of mammary gland and regional lymph outflow
      zones were studied in 16,542 patients, including 415 with punction biopsy
      performance. The mammary gland cancer diagnosis was verified at the cytological
      examination of bioptic materials in 108 patients.

PMID- 7807917
TI  - [Practical nursing. Integration of families].

PMID- 7807918
TI  - [New knowledge in the treatment of chronic wounds. Topical haemotherapy].

PMID- 7807919
TI  - [Reflections of a man of letters. Illness as an adventure].

PMID- 7807920
TI  - [Days of dying].

PMID- 7807921
TI  - [The Cancer Help Center in Bristol--a report. Multiple ways of assistance in the
      battle against cancer].

PMID- 7807922
TI  - [Nurse and midwife in India--a portrait. Organizing nursing care in Udupi].

PMID- 7807923
TI  - [Savings and quality promotion in psychiatry? Quality yes--but not at zero
      tarifs].

PMID- 7807924
TI  - [Instruments for the promotion of quality of care. Nurses are promoting quality-
      without being aware of it].

PMID- 7807925
TI  - [African lamentations in the hospital--].

PMID- 7807926
TI  - [Learning to face complex nursing situations].

PMID- 7807927
TI  - [What kind of society do we want?].

PMID- 7807928
TI  - From genotype to phenotype. Free communications presented at the 31st annual
      meeting of the Society for the Study of Inborn Errors of Metabolism. Manchester,
      7-10 September 1993.

PMID- 7807929
TI  - SSIEM Award. Impaired metabolism of leukotrienes in inherited metabolic
      disorders.

PMID- 7807931
TI  - Diagnosis of carnitine acylcarnitine translocase deficiency by complementation
      analysis.

PMID- 7807930
TI  - Detection of genetic defects in Menkes disease by direct mutation analysis and
      its implications in carrier diagnosis.

PMID- 7807932
TI  - Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency due to heterozygosity for
      the common mutation and an allele resulting in low levels of MCAD mRNA.

PMID- 7807933
TI  - Prenatal diagnosis of a defect in medium-chain fatty acid oxidation.

PMID- 7807934
TI  - Secondary 3-hydroxydicarboxylic aciduria mimicking long-chain 3-hydroxyacyl-CoA
      dehydrogenase deficiency.

PMID- 7807935
TI  - Fatal cardiomyopathy associated with 3-hydroxy-3-methylglutaryl-CoA lyase
      deficiency.

PMID- 7807936
TI  - Complex I deficiency with diabetes, Fanconi syndrome and mtDNA deletion.

PMID- 7807938
TI  - Mitochondrial oxidative phosphorylation in digitonin-permeabilized chorionic
      villus fibroblasts: a new method with potential for prenatal diagnosis.

PMID- 7807937
TI  - Muscle cytochrome c oxidase deficiency in two Italian patients with ethylmalonic
      aciduria and peculiar clinical phenotype.

PMID- 7807939
TI  - Polarographic studies of saponin-skinned muscle fibres in patients with
      mitochondrial myopathies.

PMID- 7807940
TI  - Searching for mutations in the arylsulphatase A gene.

PMID- 7807941
TI  - Human alkyldihydroxyacetonephosphate synthase deficiency: a new peroxisomal
      disorder.

PMID- 7807942
TI  - A new variant of Zellweger syndrome with normal peroxisomal functions in cultured
      fibroblasts.

PMID- 7807944
TI  - Structural anomalies in patients with inherited metabolic diseases.

PMID- 7807943
TI  - Measurement of plasma very long-chain fatty acids as a preliminary screening
      procedure for the diagnosis of peroxisomal disorders.

PMID- 7807945
TI  - Fructose-1,6-bisphosphatase deficiency: severe phenotype with normal leukocyte
      enzyme activity.

PMID- 7807946
TI  - Rapid identification of primary hyperoxaluria type I patients using a novel,
      fully automated method for measurement of hepatic alanine: glyoxylate
      aminotransferase.

PMID- 7807947
TI  - Biogenic amine metabolite patterns in the urine of monoamine oxidase A-deficient
      patients. A possible tool for diagnosis.

PMID- 7807948
TI  - Prenatal diagnosis of non-ketotic hyperglycinaemia: experience in 50 at-risk
      pregnancies.

PMID- 7807949
TI  - Immune function in prolidase deficiency.

PMID- 7807950
TI  - Effect of L-dopa on pattern visual evoked potentials (P-100) and
      neuropsychological tests in untreated adult patients with phenylketonuria.

PMID- 7807951
TI  - Maternal PKU Collaborative Study: pregnancy outcome and postnatal head growth.

PMID- 7807952
TI  - Frequency of 12 mutations in 114 children with phenylketonuria in the Midwest
      region of the USA.

PMID- 7807953
TI  - Mutation screening versus gene scanning for genotyping phenylketonuria patients.

PMID- 7807954
TI  - Relation between phenylalanine hydroxylase genotypes and phenotypic parameters of
      diagnosis and treatment of hyperphenylalaninaemic disorders. German Collaborative
      Study of PKU.

PMID- 7807955
TI  - Phenotype distribution in the Spanish phenylketonuria population and related
      genotypes.

PMID- 7807956
TI  - Heterogeneity of phenylketonuria in Belgium at the genotype-phenotype level.

PMID- 7807957
TI  - Genetic and neurological evaluation of untreated and late-treated patients with
      phenylketonuria.

PMID- 7807958
TI  - Cognitive development related to metabolic phenotype and mutation genotype in 25
      Hungarian patients with phenylketonuria.

PMID- 7807959
TI  - Association between mutations and the variable number tandem repeat alleles in a
      sample of Turkish phenylketonuria patients.

PMID- 7807960
TI  - Genotype-phenotype correlation in 11 Romanian PKU families.

PMID- 7807961
TI  - Geographical distribution of the P281L mutation at the phenylalanine hydroxylase
      locus: possible origin in southeastern Europe.

PMID- 7807962
TI  - Different phenotypic manifestations associated with identical phenylketonuria
      genotypes in two Spanish families.

PMID- 7807963
TI  - Neointima and arterial injury: dogs, rats, pigs, and more.
AB  - Animal models have generated conflicting data regarding human restenosis. Many of
      these discrepancies can be explained on the basis of experimental methodology, or
      on improper extensions of animal data to human trials. However, fundamental
      differences clearly exist in neointimal formation across species. These relate
      not only to the quantity of neointima, but also to the histopathology as
      neointima forms. In order to design effective strategies against restenosis, the
      aggregate knowledge from all animal models must be carefully examined and
      integrated. The pathophysiology of neointimal formation across species must also
      be better understood in a unified form. Limitations of the existing animal
      models, and their relationship to human coronary disease and its treatment by
      percutaneous interventions, remain poorly understood. A solution to restenosis
      must lie in a detailed understanding of the events causing neointimal thickening,
      vascular remodelling, cellular proliferation, and matrix formation. Once the
      contribution of each is understood, interventions can be strategically planned,
      demonstrated in animal models, and successfully translated to human therapy.

PMID- 7807964
TI  - Heparin selectively inhibits synthesis of tissue type plasminogen activator and
      matrix deposition of plasminogen activator inhibitor 1 by human mesangial cells.
AB  - BACKGROUND: Mesangial changes in a variety of pathologic conditions involve
      mesangial cell proliferation and mesangial matrix remodelling. Heparin has been
      shown to prevent these processes in vivo. In vitro, heparin interferes with cell
      growth, proto-oncogene expression, synthesis of specific proteins, and
      extracellular matrix composition. In some cell types, it seems to interact with
      intracellular protein kinase C-dependent pathways. The effect of heparin on the
      mesangial plasminogen activating system (tissue type plasminogen activator, t-PA,
      and plasminogen activator inhibitor type 1, PAI-1), which is thought to be
      involved in matrix remodelling, has not been previously reported. EXPERIMENTAL
      DESIGN: Cultured human mesangial cells were stimulated by 10% fetal calf serum
      (FCS) or 16 nM phorbol myristate acetate (PMA) in the presence or absence of
      anticoagulant or nonanticoagulant heparins. Cell proliferation, synthesis of t-PA
      and PAI-1, cell morphology, and PAI-1 matrix deposition were studied using cell
      counting, [3H]thymidine incorporation, specific t-PA and PAI-1 enzyme-linked
      immunosorbent assay, Northern blot analysis, light microscopy, immunofluorescence
      and immunogold silver staining with combined bright-field and epipolarization
      microscopy. RESULTS: Heparin partially inhibited FCS-stimulated cell growth but
      not PMA-induced thymidine incorporation. FCS and PMA stimulated t-PA (p < 0.05
      and p < 0.01, respectively) and PAI-1 synthesis (p < 0.05 and p < 0.01
      respectively). Heparin selectively and partially inhibited FCS-stimulated t-PA,
      but not PAI-1 synthesis. It has no effect on PMA-stimulated t-PA or PAI-1
      synthesis but prevented cell shape-changes induced by PMA, suggesting that
      heparin inhibits some but not all protein kinase C (PKC)-dependent effects and
      that heparin block in t-PA synthesis is distal to PKC activation. Heparin
      decreased PAI-1 matrix accumulation. Similar distal to PKC activation. Heparin
      decreased PAI-1 matrix accumulation. Similar results were observed with
      anticoagulant and nonanticoagulant heparin fragments. CONCLUSIONS: In human
      mesangial cells, anticoagulant and nonanticoagulant heparin exert an
      antiproliferative effect and may prevent mesangial matrix changes by decreasing
      FCS-stimulated t-PA synthesis and PAI-1 deposition in the matrix. Heparin is able
      to inhibit PKC-dependent cell shape changes but not PKC-dependent t-PA or PAI-1
      synthesis. It also inhibits PKC-independent cell proliferation and t-PA
      synthesis. These results suggest multiple intracellular sites of action for
      heparin, unrelated or distal to PKC activation.

PMID- 7807965
TI  - Expression of gelatinases A and B and their tissue inhibitors by cells of early
      and term human placenta and gestational endometrium.
AB  - BACKGROUND: Human placentation is mediated by fetal trophoblastic cells that
      invade the maternal uterine endometrium. Trophoblast invasion requires a
      precisely regulated secretion of specific proteolytic enzymes able to degrade the
      endometrial basement membrane and extracellular matrix. EXPERIMENTAL DESIGN:
      Several studies have documented the key roles of matrix metalloproteinases and
      their tissue inhibitors in the invasion of various matrices by cultured
      trophoblasts. In vitro studies suggest that placentation could result from a
      balance between the secretion of these enzymes by trophoblast cells and their
      inhibition by the natural tissue inhibitors (TIMPs) produced by maternal decidual
      cells. The precise localization and levels of expression of these proteins that
      account for and control invasion during human placentation in vivo however, have
      not been described. We have evaluated, in vivo, by immunohistochemistry, Northern
      blot analysis and in situ hybridization, the expression of two metalloproteinases
      (gelatinases A and B) and their two tissue inhibitors (TIMPs 1 and 2) in
      placental villi and placental beds of first and third trimesters of normal
      pregnancy. RESULTS: Human first trimester intermediate trophoblast produced both
      gelatinases A and B; these two gelatinases were respectively less and no more
      detected at term in these cells. We found that both TIMP1 and 2 were also
      expressed in maternal decidual cells with a dramatic increase of TIMP1 at the
      term of pregnancy. In floating villi, gelatinase A and TIMP1 were localized in
      the stromal compartment, whereas gelatinase B and TIMP2 were codistributed in
      trophoblast cells. CONCLUSIONS: The gelatinases A and B and their tissue
      inhibitors are thus expressed by specific cells in early and late placental beds
      and villi. This pattern of expression varies during pregnancy. Therefore, our
      morphologic study supports biologic findings suggesting that these proteins may
      participate in placentation.

PMID- 7807966
TI  - Neoplastic hormone-producing cells of the placenta produce and secrete
      parathyroid hormone-related protein. Studies by immunohistology, immunoassay, and
      polymerase chain reaction.
AB  - BACKGROUND: Parathyroid hormone-related protein (PTHrP) was originally discovered
      as a product of tumors associated with hypercalcemia. Subsequent studies have
      demonstrated the widespread production of PTHrP in both fetal and adult tissues,
      among them the placenta, where it has been identified in amniotic epithelial
      cells and trophoblasts. However, studies of PTHrP production by the neoplastic
      placenta have not been reported. EXPERIMENTAL DESIGN: We have studied placental
      cells and tissues for PTHrP by immunohistology, immunoassay, and the polymerase
      chain reaction. We studied normal placenta, placenta neoplasia, and placental
      cell lines grown in culture. RESULTS: Our studies in abnormal placenta
      demonstrate that PTHrP is produced by chorioangioma, choriocarcinomas, and
      hydatidiform moles, indicating that PTHrP may be a marker for neoplasia of the
      placenta. Our studies in normal placenta demonstrate that PTHrP is produced by
      several placental cell types, including, syncytiotrophoblast, intermediate
      trophoblasts, cytotrophoblasts, and amniotic epithelium, suggesting an important
      role for this protein in several aspects of placental function. Cell lines
      derived from trophoblasts and amniotic epithelium also produced PTHrP and
      secreted it into culture medium. Polymerase chain reaction with PTHrP coding
      sequence primers demonstrated the appropriate polymerase chain reaction product
      in these placental cells. CONCLUSIONS: The production of PTHrP by several normal
      and abnormal placental cell types is evidence for an important function for PTHrP
      in normal and neoplastic placenta.

PMID- 7807967
TI  - AL amyloidosis. Characterization of amyloidogenic cells by anti-idiotypic
      monoclonal antibodies.
AB  - BACKGROUND: AL amyloidosis is characterized by systemic tissue deposition of
      monoclonal Ig light chains synthesized by a bone marrow plasma cell (PC) clone
      whose biologic characteristics remain undetermined. EXPERIMENTAL DESIGN: Anti
      idiotypic (anti-Id) monoclonal antibodies (MoAbs) were used as specific probes to
      identify and study amyloidogenic cells in two patients by means of
      immunofluorescence methods. These MoAbs recognized populations of bone marrow pre
      PC, PC, and peripheral blood lymphocytes. To test whether the circulating Id+
      lymphocytes were capable of PC differentiation, peripheral blood lymphocytes were
      incubated with the differentiation-inducing agents, interleukin-3 and interleukin
      6 in liquid culture. Preincubation with the anti-Id MoAb and complement was used
      to inhibit formation of Id+PC in vitro. RESULTS: The anti-Id MoAb identified
      three types of cells in the bone marrow with cytoplasmic Ig having the same
      isotype as the monoclonal component: a) lymphoid cells, that were slightly larger
      than common peripheral blood lymphocytes (47% CD45RA+, 28% CD45R0+, 97% CD38-,
      100% CD10-, 100% mu-chain-); b) lymphoplasmacytoid cells with more abundant
      cytoplasm and Id+ Ig (CD45RA-, CD45RO-, CD10-, 53% CD38+); 3) mature PC that were
      very similar to normal PC in morphology and antigenic profile (CD38+, PCA1+, CD56
      ). A different picture was seen when anti-Id MoAb were used to detect peripheral
      blood Id+ elements: analysis revealed a population of mature resting surface Ig+
      B lymphocytes. Circulating Id+ lymphocytes differentiated in vitro to PC and
      lymphoplasmacytoid cells that were very similar to those present in the bone
      marrow. A significant reduction in the number of Id+ PC was obtained after
      incubation with the anti-Id MoAb and complement. CONCLUSIONS: This study shows
      that the amyloidogenic cell clone is constituted by at least the following cell
      populations: a fraction of bone marrow cells (lymphoid, lymphoplasmacytoid cells
      and PC) and a subset of peripheral blood post-switched B lymphocytes. The results
      suggest a relationship among these cells, indicating that circulating Id+
      lymphocytes may be the possible precursors of the more differentiated bone marrow
      population.

PMID- 7807968
TI  - Biologic effects of recombinant human interleukin-12 in squirrel monkeys
      (Sciureus saimiri).
AB  - BACKGROUND: Interleukin-12 is a novel heterodimeric cytokine that stimulates the
      proliferation of activated T and NK cells and induces lymphokine-activated killer
      cell activity in vitro. To investigate the biological effects of recombinant
      human IL-12 (rHuIL-12) in vivo, two exploratory studies were conducted in
      squirrel monkeys (Sciureus saimiri), which have been shown to be
      pharmacologically responsive to rHuIL-12 in vitro. EXPERIMENTAL DESIGN: In the
      first study, 18 monkeys (3/sex/group) were given daily subcutaneous injections of
      0 (vehicle control), 10, or 50 micrograms/kg/day rHuIL-12 for 14 days. In the
      second study, 18 monkeys were given 0, 0.1, or 1 micrograms/kg/day rHuIL-12 for
      14 days The animals were monitored for clinical signs, hematology and clinical
      chemistry changes, and sacrificed on day 15 to evaluate gross and histopathologic
      changes. One monkey in the high dose group was sacrificed moribund on day 14.
      RESULTS: Monkeys given rHuIL-12 had dose-related hematologic changes
      characterized by mild to moderate anemia and leukocytosis. Serum chemistry
      changes included hypoproteinemia, hypoalbuminemia, hypophosphatemia, and
      hypocalcemia. Gross pathologic findings included generalized lymph node
      enlargement and splenomegaly with pulmonary edema and peritoneal effusions in two
      high dose monkeys. Dose-related histopathologic findings included thymic cortical
      atrophy, splenic lymphoid hyperplasia with histiocytic hyperplasia and
      extramedullary hematopoiesis of red pulp, Kupffer cell hypertrophy and
      hyperplasia, trilineage bone marrow hyperplasia, and reactive hyperplasia of
      lymph nodes. Animals in the 10 and 50 micrograms/kg/day dose groups developed
      high titers of anti-rHuIL-12 antibodies by day 15. CONCLUSIONS: These studies
      indicate that rHuIL-12 is bioactive over a wide dose range and induces prominent
      hyperplasia of hematopoietic and lymphohistiocytic tissues in squirrel monkeys.
      Moreover, positive immunomodulatory activity (enhanced lymphocyte lytic activity)
      was detected at a dose of rHuIL-12 that is 500-fold less than the dose causing
      severe toxicity.

PMID- 7807969
TI  - Clonality of combined testicular germ cell tumors of adults.
AB  - BACKGROUND: Recently we have shown, by combining in situ hybridization and
      immunohistochemistry, that carcinoma in situ (CIS) adjacent to seminoma (CIS/SE),
      like SE, usually contains three copies of the centromeric region of chromosome
      15/tumor cell. In contrast, CIS adjacent to nonseminomatous testicular germ cell
      tumors of adults (CIS/NS), as well as NS itself, have two copies. EXPERIMENTAL
      DESIGN: In the present study we have used this approach to investigate the clonal
      origin of the SE and NS components of combined tumors (CTs). We counted the
      number of copies of chromosome 15 centromeric regions in tumor cell nuclei of the
      CIS, SE, and NS components of nine CTs. RESULTS: We show that the number of
      copies of centromeric regions of chromosome 15 in both the SE and the NS
      component, and the adjacent CIS of the same CT, may be high (SE-pattern) or low
      (NS-pattern). In two cases, the copy numbers were high in the SE component and
      its adjacent CIS, and low in the NS component and its adjacent CIS. CONCLUSIONS:
      The data suggest that in most CTs the SE and the NS components have a monoclonal
      origin, and that karyotype evolution in CIS and the invasive tumor is very
      similar.

PMID- 7807970
TI  - Collagen type I is not under autocrine control by transforming growth factor-beta
      1 in normal and scleroderma fibroblasts.
AB  - BACKGROUND: The ability of transforming growth factor-beta (TGF-beta) to induce
      synthesis of extracellular matrix proteins stimulated this study in which we
      address the hypothesis that TGF-beta can induce, in normal fibroblasts, the
      sustained, elevated collagen synthesis characteristic of the scleroderma
      fibroblast. EXPERIMENTAL DESIGN: Fibroblasts were studied for synthesis of and
      responsiveness to TGF-beta. Secreted TGF-beta levels were determined in a
      bioassay and at the transcriptional level in a series of scleroderma (SSc) and
      normal fibroblasts. The ability of cells to interact functionally with a 3
      dimensional collagen matrix after TGF-beta treatment was examined. The kinetics
      of TGF-beta-induced fibrosis in fibroblasts was studied. RESULTS: SSc fibroblasts
      were not characterized by elevated TGF-beta synthesis. There was no evidence of
      coordinate regulation of TGF-beta and collagen over passage number. Repeated
      pulses of 200 pM of TGF-beta did not significantly induce sustained procollagen
      alpha 1(I) mRNA synthesis in normal fibroblasts, and this treatment did not
      significantly alter the characteristics of normal fibroblasts in a collagen gel.
      mRNA for both collagen and TGF-beta type II receptor was induced by TGF-beta in
      both SSc and control cells. SSc fibroblasts were found to have an impaired
      ability to activate the small latent complex of TGF-beta. CONCLUSIONS: Our data
      give no support to the hypothesis that TGF-beta can maintain the SSc phenotype in
      vitro or that it is able to induce this phenotype. The inducibility of TGF-beta
      receptor mRNA in SSc fibroblasts after exposure to TGF-beta suggests that the
      lack of sustained elevation in collagen synthesis is not due to lack of
      responsiveness by the fibroblasts but is rather a reflection of the transient
      nature of TGF-beta-induced fibrosis.

PMID- 7807971
TI  - Biodegradation of magnetite dextran nanoparticles in the rat. A histologic and
      biophysical study.
AB  - BACKGROUND: Superparamagnetic iron oxide particles represent a new class of
      contrast agents that increase the detectability of hepatic and splenic tumors by
      magnetic resonance imaging (MRI). Magnetite dextran nanoparticles, a preparation
      with a small mean particle diameter in solution and null zeta potential present
      high safety margin and efficacy. The purpose of this investigation was to define
      the main steps of the metabolism of the iron oxide crystals. EXPERIMENTAL DESIGN:
      Rats were intravenously administered a single small dose of 59Fe-labeled MD3 (3
      mg Fe/kg), and the biodistribution of 59Fe was investigated in the different
      organs from 2 hours to 25 days postinjection. Magnetic susceptibility studies
      were conducted in parallel to light microscopy and immunohistochemistry from day
      1 to day 14 after administration. RESULTS: Most of the dose accumulated in the
      carcass (45%), liver (7%), and spleen (7%) in the first 2 hours. In the spleen, a
      continuously iron uptake was observed up to 48 hours (44%), then decreased to 25
      days (22%). The splenic magnetic susceptibility dropped sharply during the first
      days and then more slightly until day 14. In the liver and blood, the 59Fe-level
      decreased at 24 hours and then increased until day 25 (11% and 27%,
      respectively). Histochemistry features essentially confirmed the radiotracer data
      and showed that iron oxide cores were accumulated into the Kupffer cells and the
      macrophages of the splenic marginal zone. With time, the number of the granules
      was decreased whereas the fine iron granules appeared in the cytoplasm.
      Immunopositive staining for ferritin was markedly increased in the liver
      hepatocytes to 3 days after injection, and in the splenic marginal zone
      macrophages to 14 days after injection. CONCLUSIONS: The data point to the early
      biodegradation of the iron oxide crystals. MD3 thus appear as an interesting
      biodegradable new contrast agent first devoted to magnetic resonance imaging of
      liver and spleen diseases that could be further extended to heart, kidneys, and
      other organs.

PMID- 7807972
TI  - A model of DNA aneuploidization and evolution in colorectal cancer.
AB  - BACKGROUND: Extensive chromosome and DNA content heterogeneity within and between
      human solid tumors has been observed using both classical karyotype and DNA
      cytometry. Experimental evidence suggests, at least in some tumor types, that DNA
      stemline heterogeneity in tumor progression is according to a three-compartment
      model with diploidy shifting to tetraploidy and then to hypotetraploidy.
      EXPERIMENTAL DESIGN: The human colorectal adenoma-carcinoma sequence appears as
      one of the most potentially informative systems for the study of DNA stemline
      heterogeneity in human tumors since adenomas, adenomas with early cancer, and
      adenocarcinomas in nontreated patients represent clear morphologically distinct
      stages of tumor progression. The quantitative measurement of DNA content in the
      G0.1 phase of the cell cycle was performed by high resolution flow cytometry in a
      large number of cases using multiple fresh or frozen samples. RESULTS: The
      distribution of the degree of DNA aneuploidy values, also known as DNA index, (DI
      not equal to 1) among 467 human precancer and cancer colorectal lesions was
      clearly nonrandom and showed modes at DI = 0.9, 1.2, 1.5, 1.8, and 2.2 with a
      clear valley at DI = 1.3. Whereas DNA aneuploid subclones within early lesions
      were up to about 80% near-diploid (DI < or = 1.3), DNA subclones within advanced
      cancer were in the vast majority with DI = 1.5-1.8 and, in a small fraction, with
      DI > 2. In addition, in adenomas with early cancer, which represent a link in
      colorectal tumor progression, early and late DNA stemlines often coexisted.
      CONCLUSIONS: The natural history of the colorectal adenoma-carcinoma sequence
      appears to be characterized by near-diploid subclones as early events and by late
      stage hypotetraploidy. A new model is proposed that predicts the origin of the
      near-diploid subclones by "loss of symmetry" in cell division and their evolution
      (in particular hypodiploid) to the late-stage hypotetraploidy by
      tetraploidization. This model agrees with recent data associating molecular
      biology events, cytogenetic data, and DNA stemline heterogeneity in colorectal
      and other tumor systems.

PMID- 7807973
TI  - A new double labeling technique for combined in situ hybridization and
      immunohistochemical analysis.
AB  - BACKGROUND: A reliable, sensitive, and specific double labeling technique is
      required that allows the simultaneous visualization of in situ hybridization
      products and antigens. Currently used double labeling techniques are limited by
      various problems including the numerous disadvantages associated with radioactive
      labels, the time-dependent loss of fluorescence signals, and the high background
      that is associated with various peroxidase techniques. Therefore, the aim of this
      study was to develop an improved double labeling technique. EXPERIMENTAL DESIGN:
      Riboprobes were used for detection of mRNA of cathepsin D, vascular cell adhesion
      molecule, and endothelial leukocyte adhesion molecule in in situ hybridization
      and monoclonal antibodies specific for macrophages and basement membranes
      (collagen type IV) for immunohistochemical analysis. The in situ hybridization
      and immunohistochemical analysis were used to characterize cathepsin D messenger
      ribonucleic acid (mRNA) in macrophages expressing cells and the expression of
      adhesion molecule mRNA in endothelial cells delineated by the vascular basement
      membrane expressing collagen type IV. RESULTS: The application of in situ
      hybridization detection systems before immunohistochemical analysis was shown to
      give reliable results. In situ hybridization with digoxigenin labeled riboprobes
      using alkaline phosphatase linked Fab fragments visualized by 4-nitro blue
      tetrazolim chloride/5-bromo-4-chloro-3-indolphosphate combined with
      immunohistochemical detection of the antigen by the alkaline phosphatase anti
      alkaline phosphatase-technique with new fuchsin as substrate is a reliable double
      labeling technique. Using this protocol, we could show that the reaction product
      is stable, there is virtually no background, and both reaction products can be
      easily distinguished. Vascular cell adhesion molecule-1 mRNA is expressed only in
      endothelial cells and certain fibroblast-like cells that do not label with
      antibodies against macrophages, whereas cathepsin D mRNA is coexpressed with
      macrophages. We also demonstrated that endothelial leukocyte adhesion molecule-1
      mRNA is strongly expressed in endothelial cells that can be localized within the
      boundaries of the vascular basement membrane. CONCLUSIONS: A new and reliable
      double labeling technique for the simultaneous evaluation of in situ
      hybridization and immunohistochemical analysis is described that is suitable for
      various applications.

PMID- 7807974
TI  - Compensatory growth of glomeruli.

PMID- 7807975
TI  - Romanticism and self-esteem among pregnant adolescents, adolescent mothers, and
      nonpregnant, nonparenting teens.
AB  - Feelings of romanticism and self-esteem among pregnant adolescents, adolescent
      mothers, and a control group of nonpregnant, nonparenting adolescents were
      investigated. The Bachman Self-Esteem Scale (Bachman, O'Malley, & Johnston, 1978)
      and the Dean Romanticism Scale (Dean, 1961) were distributed to 649 U.S. female
      adolescents--255 pregnant adolescents, 121 adolescent mothers, and 273 teenagers
      in the control group. For romanticism, the results indicated a significant main
      effect for group (pregnant teens, teen mothers, and a control group consisting of
      nonpregnant, nonparenting teenagers) and ethnicity (White, Hispanic, African
      American, and Asian) but not for age (13 to 15 years and 16 to 19 years). The
      pregnant teens and teen mothers thus had a higher degree of romanticism than the
      control group did. For self-esteem, there was a significant main effect for race,
      but not for group or for age. This main effect was qualified by a significant
      interaction between ethnicity and age.

PMID- 7807976
TI  - Restraint and perception of body weight among British adults.
AB  - A sample of 533 adults (268 women and 265 men) representative of the general
      population of Great Britain were interviewed so that the extent and effects of
      restraint, using the Dutch Eating Behaviour Questionnaire (DEBQ; Van Strien,
      Frijters, Bergers, & Defares, 1986) and the extent of overestimation of body
      weight could be examined. High-restraint subjects reported more guilt about food
      and eating and a greater likelihood of overeating in reaction to dysphoric mood,
      and they were more apt to overestimate their body size. Women reported
      significantly higher restraint, more guilt after eating in various types of
      social situations, and more overeating in reaction to dysphoric mood. Higher
      social class was associated with reports of guilt about a greater number of foods
      and with reports of more overeating when under stress or tired. Age was
      positively associated with guilt and negatively associated with overeating in
      reaction to being under stress, tired, or depressed.

PMID- 7807977
TI  - Racially based trust expectancies of Native American and Caucasian children.
AB  - Native American and Caucasian children attending fourth or fifth grade in same
      race or mixed-race Canadian schools judged themselves and the other group with
      respect to trust. As hypothesized, the children displayed same-race trust
      expectancies: Native American children expected a Caucasian child to be less
      likely to keep promises, keep secrets, and tell the truth than a Native American
      child. The Caucasian children displayed the opposite pattern of expectancies. The
      same-race pattern of trust was less evident in mixed-race schools than in same
      race schools but, consistent with the behavioral disconfirmation hypothesis, only
      for expectancies of promise keeping.

PMID- 7807978
TI  - Using moral and epistemological reasoning as predictors of prejudice.
AB  - Regression analyses indicated that a sample of American students who were
      humanitarian-egalitarian in their outlook, who possessed a high level of
      education, who were less supportive of the Protestant Ethic, and who employed a
      high percentage of relativism in their decision making were more likely to have
      positive attitudes toward minorities than those not possessing such attributes.
      Age proved to be a predictor of negative attitudes toward minorities. The
      findings help provide a rationale for further investigation of the relationship
      between moral and epistemological reasoning as well as for implementation of
      moral education programs as means to reduce negative racial attitudes.

PMID- 7807979
TI  - Ways of coping among HIV-infected individuals.
AB  - A sample of 85 HIV-infected Americans completed a questionnaire that assessed
      coping styles, depression, and physical illness. We examined the relationships of
      emotion-focused coping and problem-focused coping to depression and physical
      illness. A two-way analysis of variance revealed a significant main effect for
      emotion-focused coping on depression: Those who used more emotion-focused coping
      also experienced more depression. No interaction effects or main effects for
      problem-focused coping were found.

PMID- 7807980
TI  - The development and testing of a diagnostic scale for incest survivors.
AB  - A scale (Diagnostic Scale for Incest Survivors: DSIS) was developed for adult
      women who experienced incest during childhood. Items were obtained from research
      on post-traumatic stress, personality disorders, standard psychiatric categories,
      and clinical observations. The scale was administered to a sample of Australian
      women and was found to possess satisfactory reliability and validity.

PMID- 7807981
TI  - Influence of motivation and gender on secondary school students' academic
      performance in Nigeria.

PMID- 7807982
TI  - Gender differences in work values and personality characteristics among Indian
      executives.

PMID- 7807983
TI  - Mood and persuasion: independent effects of affect before and after message
      processing.

PMID- 7807984
TI  - Lymph flow and lymphatic drainage of inflammatory cells from the peritoneal
      cavity in a casein-peritonitis model in sheep.
AB  - The purpose of this study was to characterize the cellular responses in the
      peritoneal cavity and draining lymph in a sterile peritonitis model in conscious
      sheep. Lymph was collected from lymphatics that drained the peritoneal space
      (caudal mediastinal and thoracic ducts) as well as from lymph vessels that
      drained peripheral tissues (prescapular). Casein was used as the inflammatory
      agent. Dialysis solution (Dianeal 4.25%) containing 1g% casein and 25 microCi
      125I-human serum albumin was infused into the peritoneal cavity in 50 ml/kg
      volumes. Peritoneal volumes increased from a mean infused volume of 1572 +/- 51
      ml to a maximum of 2119 +/- 77 ml at 3 hours. Over 6 hours, the number of
      macrophages and lymphocytes in the peritoneal cavity remained relatively constant
      but the number of neutrophils increased from 9.9 +/- 4.2 x 10(7) to 9.2 +/- 1.9 x
      10(9) total cells. Caudal lymph which drains directly from the peritoneal cavity
      through diaphragmatic stomata, demonstrated a 5 fold increase in flow rate over 6
      hours following the Dianeal-casein infusion. Thoracic duct and prescapular flows
      declined approximately 70% and 50% respectively in the same time period. the
      concentration of lymphocytes and the lymphocyte outputs (product of volume and
      concentration) declined in all lymph compartments. No elevations in neutrophil
      numbers in the thoracic and prescapular lymph compartments were observed but
      neutrophil output in the caudal lymph increased steadily from 3.1 +/- 1.5 x 10(6)
      to 4.6 +/- 1.3 x 10(7)/hr at the 6 hour mark. We conclude that the major route of
      removal of inflammatory cells and fluid from the peritoneal cavity is through
      diaphragmatic lymphatics.

PMID- 7807985
TI  - Evaluation of the greater omentum in the treatment of experimental lymphedema.
AB  - Despite advances in microsurgery, the most suitable operation for primary
      lymphedema remains unclear. A variety of tissue transplants and artificial
      substances have been used to facilitate drainage of peripheral lymph. The greater
      omentum, for example, has absorptive lymph draining capability, fights infection,
      and is expendable for the abdomen. Previous attempts to use the omentum in
      treatment of clinical lymphedema have, however, been disappointing. This
      discrepancy between theory and outcome prompted us to reevaluate the role of the
      omentum in the treatment of chronic lymphedema. In rabbits, mobilization of
      omentum was carefully examined by three separate techniques and the presence of
      natural lymph nodal-venous (L-V) shunts determined by an injection of Evans blue
      into the omentum with sampling later of plasma from the gastroepiploic venous
      blood. In dogs after promotion of unilateral chronic hindlimb lymphedema by soft
      tissue excision and sclerosis, the results of four methods of omental
      transplantation with or without L-V shunt for relief of lymphedema were compared.
      The results in rabbits suggest that although the greater omentum can be
      lengthened without jeopardizing its blood supply, it is inappropriate to lengthen
      it based on blood vascular arcades alone because the omental lymphatics do not
      strictly follow these arcades in the more distal portion, and with elongation,
      may be interrupted even though the blood supply remains intact. Moreover, because
      there is no natural L-V shunt within the greater omentum, the addition of a L-V
      shunt in dogs in addition to omental transplantation seems to increase
      effectiveness of the omentum for draining hindlimb lymph after its
      autotransplantation.

PMID- 7807986
TI  - Autotransplantation of the greater omentum in the treatment of chronic
      lymphedema.
AB  - We evaluated the use of transplantation of the greater omentum in the management
      of chronic lymphedema in 21 patients. The omentum provides a large surface with
      fluid absorbing capability and potentially therefore is useful in management of
      patients with primary or hypoplastic peripheral lymphatics. Based on the angio-
      and lymphangio-architecture of the gastroepiploic architecture, we used large
      segments of greater omentum as a free autotransplant with microrevascularization
      to the femoral or axillary artery and vein thereby avoiding technical drawbacks
      of a pedicle graft with the feeding vessels traversing the abdomen. Elongation of
      the omentum must be done properly because omental lymphatic arcades do not
      consistently follow the blood vascular arcades in its more distal part.
      Accordingly, if not properly mobilized the blood supply may be retained whereas
      the lymph circulation is interrupted. We combined omental implantation with lymph
      nodal-venous anastomoses using an omental vein with a nearby systemic venous
      tributary. In 19 of the 21 patients followed from 3 months to 2 years after
      operation, remission of lymphedema was good (reduction in swelling more than 50%)
      in 14 patients and satisfactory in 5 (approximately 25-50% reduction in swelling)
      with improvement gradually increasing with the passage of time.

PMID- 7807989
TI  - Skin bacterial factor in progression of filarial lymphedema.

PMID- 7807987
TI  - Massive inguinal lymphocele.

PMID- 7807988
TI  - Chromolymphography with "chlorophyll" revisited.

PMID- 7807990
TI  - Management of lymphedema.

PMID- 7807992
TI  - 12p chromosomal aberrations in precursor B childhood acute lymphoblastic leukemia
      predict an increased risk of relapse in the central nervous system and are
      associated with typical blast cell morphology.
AB  - Recently we reported cytogenetic, clinical, and immunologic data of 135 childhood
      ALL patients, who were diagnosed and treated in The Sophia Children's Hospital
      between January 1, 1980 and November 1, 1990. An increased risk for a first
      relapse in the central nervous system (CNS) was detected in a subgroup of
      childhood ALL patients with common ALL or pre-B ALL phenotype and chromosomal
      aberrations of the short arm of chromosome 12. In this paper we report clinical,
      cytogenetic, immunologic, morphologic and cytochemical data on these eight
      childhood ALL patients with aberrations of the short arm of chromosome 12 and of
      an additional four cases that were diagnosed and treated between November 1, 1990
      and February 1, 1992. We found that three out of six common ALL, two out of three
      pre-B ALL and one out of three T-ALL patients with 12p chromosomal rearrangements
      developed a first relapse in the CNS. On the contrary, the frequency of CNS
      relapse in our childhood ALL patients without 12p aberrations was 10%.
      Furthermore, morphologic and cytochemical analysis of the bone marrow smears of
      these 12 patients with aberrations of the short arm of chromosome 12 revealed
      that the nine cases with pre-B or common ALL phenotype had typical morphologic
      characteristics that are unusual for newly diagnosed childhood ALL. Typical for
      this subtype is the presence of large polymorphic blast cells without nucleoli.
      The nuclei are irregularly shaped showing folds and clefts and a stripy pattern.
      The nucleus and cytoplasm are often abundantly vacuolated. The cytoplasm has a
      foamy light-blue appearance.

PMID- 7807991
TI  - Pentostatin treatment for hairy cell leukemia patients who failed initial therapy
      with recombinant alpha-interferon: a report of CALGB study 8515.
AB  - Eighty-five hairy cell leukemia (HCL) patients who had failed initial therapy
      with recombinant alpha interferon were enrolled for pentostatin therapy. All had
      HCL confirmed by central pathology review and were eligible for evaluation. The
      median age was 55 years (range 31-83 years). Fifteen patients were between 31-
      and 40-years-old. There were 72 males (85%) and 13 females (15%). Fifty-four
      patients (64%) had prior splenectomy. All had been previously treated with
      interferon; nine had achieved a complete response (CR), 36 had a partial response
      (PR), 35 had stable disease (SD), and five patients had progressive disease.
      Patients with a CALGB performance status (PS) of 0-2 (78 patients) received 4
      mg/m2 i.v. on days 1 and 15, repeated every 4 weeks. Patients with a performance
      status of 3 or 4 (seven patients) were started at 2 mg/m2 i.v. in the absence of
      grade 3 toxicity, the dose was escalated. Complete responses were seen in 36
      patients (42.4%) and 35 patients had partial responses (41.2%) for an overall
      response rate of 83.6%. Median time to best response was 6.5 months. Eight
      patients had stable disease, and one patient had progressive disease. Three
      patients died early during the treatment phase and two were not evaluable due to
      treatment violations. Of seven patients with a CALGB performance status of 3 or
      4, there were no CRs and only two PRs. Of 31 evaluable PS 0-2 patients who had
      previously achieved only stable disease on interferon, 13 had a CR on pentostatin
      and 12 had a PR. Based on PS 0-2 patients, the median follow-up is 44 months and
      36 month remission duration and survival rates and 95% confidence intervals are
      84% (CI 68-93%) and 91% (CI 81-96%). The 36 month survival rate was 29% (CI 10
      58%) for PS 3-4 patients. Drug dosage was modified in 39 (51%) of 76 evaluable
      patients. Leukopenia and/or infection were the most frequent toxicities leading
      to a dose modification. Pentostatin is an effective agent and induces an
      excellent response in relapsed HCL patients previously treated with alpha
      interferon (alpha-IFN).

PMID- 7807993
TI  - Therapy-related leukemia and myelodysplastic syndrome in chronic lymphocytic
      leukemia.
AB  - A retrospective analysis was performed to determine the incidence and clinical
      features of acute myelogenous leukemia/myelodysplastic syndrome (AML/MDS)
      developing in chronic lymphocytic leukemia (CLL) patients. AML/MDS occurred in
      3/1374 CLL patients seen at a single institution between 1972 and 1992. The
      median follow-up exceeded 7 years and 72% of these patients had received prior
      alkylating agent therapy. The expected number of AML/MDS developing in a general
      population of the same size was 1.2 as calculated from the National Cancer
      Institute's Surveillance, Epidemiology, and End Results (SEER) Program data
      (observed-to-expected ratio = 2.49; 95% confidence interval = 0.9-7.3; p = 0.12).
      Although, not included in the incidence calculation, four patients with CLL were
      referred at the time of development of AML/MDS. CLL and AML/MDS were diagnosed
      concurrently in two patients. Three of the patients had received no prior
      alkylating agents. The median survival was 17 months in patients who had received
      no prior treatment, and 5 months in those who had received prior chemotherapy.
      Our results suggest that patients with CLL in whom AML/MDS develops have similar
      prognoses to other patients with AML/MDS. Furthermore, this analysis does not
      provide evidence for a heightened risk of AML/MDS in CLL patients, despite
      treatment with known leukemogenic agents.

PMID- 7807994
TI  - Fluorescence-labeling of nicks in DNA from leukemic blast cells as a measure of
      damage following cytosine arabinoside. Application to the study of regulated drug
      sensitivity.
AB  - Damage to DNA can be assessed using a technique for labeling nicks in DNA by
      incubating paraformaldehyde-fixed cells in a mixture of biotin-labeled dUTP, dATP
      with dNTP and DNA polymerase I. The addition of labeled nucleotides can then be
      identified by fluorescence by their reaction with streptavidin. We have used this
      method to examine damage to the DNA of OCI/AML-2 cells caused by cytosine
      arabinoside (ara-C) and the effects of hydrocortisone and retinoic acid on this
      damage (regulated drug sensitivity). Concurrent measurements of clonogenic cells
      were used to allow a comparison of damage as shown by labeled nicks in DNA with
      loss of colony-forming capacity. Both methods gave comparable ara-C dose-response
      curves, for cells incubated with the drug for 24 h. Both methods showed that
      exposure of OCI/AML-2 cells to hydrocortisone before ara-C greatly reduced the
      toxicity of the drug; and that retinoic acid given after ara-C increased both its
      lethal effects on colony formation and the extent of DNA damage as assessed by
      labeled nicks. Clonogenic assays required for colony formation are not readily
      adapted to the study of development and repair of damage. The labeled nick assay
      is suitable for such kinetic studies. OCI/AML-2 cells were exposed in suspension
      to either hydrocortisone before ara-C or retinoic acid after ara-C. At 24 h
      intervals thereafter, cells were harvested, assayed by both methods, and
      recultured after dilution to the original cell concentration. In cultures exposed
      only to ara-C (controls), the number of cells with labeled nicks increased during
      the first 24 h and cells with damaged DNA could be detected for 48-72 h,
      depending on the ara-C dose in spite of the dilution at each passage. OCI/AML-2
      cells exposed to hydrocortisone before drug showed fewer nick-labeled cells than
      controls at the first observation and damaged cells rapidly disappeared from the
      population with increasing time. For cells treated with retinoic acid after ara
      C, the nick-labeled cell population was greater than controls and remained
      greater throughout subsequent observations. We propose that in the control
      cultures, sublethal damage either became lethal with time and was seen as
      increased numbers of cells with damaged DNA, or alternatively, sublethal damage
      was repaired. From this point of view we consider that hydrocortisone promotes
      repair of sublethal damage while retinoic acid inhibits repair.

PMID- 7807995
TI  - VP-16-mediated cytotoxicity is modulated by interleukin-3 in a growth factor
      dependent leukemic cell line.
AB  - A growth factor-dependent cell line (TF-1) was treated with interleukin-3 (IL-3)
      or medium in combination with variable doses of VP-16 to test whether the
      latter's cytotoxicity can be modulated by IL-3. The results demonstrated that an
      augmented cell death occurred with TF-1 cells when pre-incubated for 24 h with IL
      3 followed by treatment with VP-16 (10 micrograms/ml) for 1 h. The increased cell
      death could not be ascribed to an increased number of apoptotic cells as measured
      with the acridine orange method. However, the IL-3 treatment coincided with an
      upregulation of DNA topoisomerase II alpha (Topo II alpha) at mRNA and protein
      level after 24 h, which was preceded by an upregulation of c-myc mRNA. In
      contrast, Topo II beta did not demonstrate an upregulation at mRNA level in
      response to IL-3 stimulation. In addition, it was shown that cells treated with
      IL-3 followed by VP-16 demonstrated a higher number of cleavable DNA complexes
      which was not due to an increased uptake of VP-16, since cellular concentrations
      of VP-16 in the presence of IL-3 or medium were 16.8 +/- 7.8 ng/10(6) cells and
      19.8 +/- 7.8 ng/10(6) cells (mean +/- SD, n = 3), respectively. These data
      indicate that IL-3 pretreatment followed by VP-16 results in an increased cell
      death due to cytotoxicity which may be ascribed to an upregulation of Topo II
      alpha.

PMID- 7807996
TI  - Regulation by retinoic acid and hydrocortisone of the anthracycline sensitivity
      of blast cells of acute myeloblastic leukemia.
AB  - The experiments reported here continue the study of regulated drug sensitivity by
      extending the observations to anthracyclines. Previous work has shown that
      hydrocortisone (HC) protects AML blast stem cells from the lethal effects of
      cytosine arabinoside (ara-C) while retinoic acid (ATRA) increases ara-C
      sensitivity; further mechanisms of regulation of ara-C sensitivity might include
      increase or decrease in repair of sublethal damage. Anthracycline dose-response
      curves are characterized by an initial shoulder, followed by exponential decrease
      in survival with increasing dose. The shoulder portion of such curves may
      indicate the accumulation of sublethal damage. We used two assays to look for
      evidence of regulation of anthracycline sensitivity by HC or ATRA; the clonogenic
      assay for blast stem cells detects drug effects on this crucial population, but
      only after several days on incubation, during which time repair might occur.
      Measurements of nicks in DNA show damage in the bulk population of cells, but
      these can be detected very soon after exposure to drug. Both methods showed the
      HC protected cells in two continuous cell lines (OCI/AML-2 and OCI/AML-5) while
      ATRA made the cells more sensitive. Blast cells freshly-obtained from six AML
      patients were also tested. Both assays showed HC protection and ATRA
      sensitization in three populations. The clonogenic assay detected both effects in
      cells from a fourth patient; the nicked DNA assay confirmed both effects in a
      fifth patient, where the results of the clonogenic assay did not reach
      statistical significance. Neither ATRA nor HC influenced the sensitivity of
      blasts from a sixth patient; but these cells were highly resistant to drug.
      Kinetic studies showed that damage persisted longer after treatment with
      anthracyclines than with ara-C. OCI/AML-2 cells treated with HC before drug
      accumulated fewer cells with nicked DNA after daunorubicin (DNR). Cells exposed
      to ATRA after DNR showed increased toxicity in kinetic experiments. We conclude
      that sensitivity to anthracyclines may be regulated by ligands for steroid
      receptors. Furthermore, since growth factors do not regulate anthracyclines'
      sensitivity, different mechanisms may be operative for the action of ligands for
      cell surface receptors. Finally, we suggest that retinoic acid might be
      considered for inclusion in standard anthracycline/ara-C regimens for the
      treatment of AML.

PMID- 7807997
TI  - Abnormally activated T lymphocytes in the spleen of patients with hairy-cell
      leukemia.
AB  - Hairy-cell leukemia (HCL) is a B-cell leukemia, but many factors argue for a T
      cell dysfunction and/or involvement in this disease. Hairy cells typically home
      in the spleen, and become circulating only late in the disease. As it is assumed
      that the T-cell abnormalities are caused by specific interactions with the hairy
      cells, we studied the immunophenotype in 17 cases (CD3, CD4, CD8, CD45R0, TCR
      gamma delta) and cytokine gene expression in four cases (IL-1 beta, IL-2, IL-3,
      IL-4, IL-6, IL-7, IL-10, IFN-gamma, TNF-alpha, GM-CSF and the receptors of IL-1
      and IL-2, using the cDNA-PCR technique) of purified T-cell fractions from hairy
      cell spleens. By Northern blot analysis, mRNA for IFN-gamma, GM-CSF, IL-10 and
      TNF-alpha was measured in purified T cells and hairy cells from three HCL
      spleens. The results of the immunophenotype and cDNA-PCR data were compared with
      ten normal spleens. Compared to blood, splenic T cells showed a reversed CD4/CD8
      ratio, a normal percentage of memory T cells, and an increase in CD3+TCR gamma
      delta + cells. Without specific induction spontaneous cytokine gene expression of
      IL-2, IL-4, IFN-gamma, and GM-CSF was seen in the purified T-cell fractions
      without signals in the purified hairy-cell fractions. mRNA expression of IFN
      gamma and GM-CSF in the T cells, and of IL-10 and TNF-alpha in the hairy cells
      was confirmed by the Northern blot technique. From these data we suggest that
      splenic T cells in HCL should not be considered as residual or recirculating T
      cells, but rather as tumor-infiltrating lymphocytes.

PMID- 7807999
TI  - Expression of myeloid antigens by blast cells in acute lymphoblastic leukemia of
      adults. The Southwest Oncology Group experience.
AB  - A subset of adult acute lymphoblastic leukemia (ALL) patients have blast cells
      which co-express myeloid-associated antigens (MY+ ALL). We have analyzed 113
      adult ALL cases for expression of MY-associated antigens (MAA). ALL was diagnosed
      by standard morphology, cytochemistry, and immunophenotype in central review. MY+
      ALL was diagnosed when > or = 20% of lymphoblasts co-expressed CD13 and/or CD33.
      Overall incidence of MY+ was 31/113 (27%). MAA expression was not significantly
      correlated with WBC, blast count, hemoglobin, or hematocrit. MY+ cases were more
      likely to express B-associated antigens, especially CALLA, and to be FAB L2, Ph+,
      or to have the BCR-ABL translocation by PCR, but these differences were not
      statistically significant. All patients were induced with a L10M regimen, and 67
      (59%) achieved CR: 43/66 (65%) of B MY neg; 14/29 (48%) of B MY+; 10/16 (63%) T
      MY neg; and 0/2 T MY+. In age-adjusted analyses CR rate did not differ
      significantly between MY+ and MY neg patients or between B- and T-cell patients.
      Of the 113 patients, 84 have died and the remaining 29 patients have been
      followed for a median of 49 months. In proportional hazards regression analyses
      adjusting for age and WBC, heterogeneity of survival among the four groups was
      statistically significant (p = 0.021), largely due to MY status. The mortality
      rate was 85% greater for MY+ patients compared to MY neg patients (two-tailed p =
      0.013). By contrast, survival did not vary significantly between B- and T-cell
      patients. The data indicate that MAA expression is useful for predicting overall
      survival of adult patients with ALL treated in a L10M protocol. As a predictive
      factor MAA expression is comparable to the WBC and superior to the more standard
      stratification by B- or T-cell markers for this group of patients.

PMID- 7807998
TI  - Differential expression of c-myc protein in B and T lymphocytes.
AB  - Overexpression of c-myc may play a role in the multistep pathogenesis of B- and T
      cell malignancies. To determine whether this expression is inappropriate requires
      information on the normal cellular counterparts. There is no agreement in the
      literature on the levels of expression of c-myc mRNA and protein in normal
      peripheral blood lymphocytes and there are no reports on the differential
      expression in different lymphocyte populations. The aim of this study was to
      assess the state of c-myc expression in normal peripheral blood lymphocytes at
      the single cell level by immunocytochemistry and flow cytometry. Two monoclonal
      antibodies against c-myc and specific peptide inhibition controls were tested in
      mononuclear cells from nine healthy volunteers and the HL60 cell line. The
      expression of c-myc in B- and T-lymphocyte subsets was studied by two-colour
      immunocytochemistry and flow cytometry. Using calibrated reference standards, we
      quantified the c-myc protein and results were referred as molecules of equivalent
      soluble fluorochrome. Almost all lymphocytes express c-myc by both techniques.
      Two patterns of nuclear staining (weak and strong) were found by
      immunocytochemistry and this was confirmed by two peaks of fluorescence intensity
      by flow cytometry. Double immunostaining showed that the stronger pattern of c
      myc staining corresponds to B lymphocytes and the weak one to T cells.
      Quantification confirmed these results which demonstrated a statistically
      significant difference in the expression of c-myc in these two lymphocyte
      populations (p < 0.005). Our results demonstrate for the first time that normal
      circulating B cells express higher levels of c-myc protein than T lymphocytes.

PMID- 7808000
TI  - Expression of the CEA gene family members NCA-50/90 and NCA-160 (CD66) in
      childhood acute lymphoblastic leukemias (ALLs) and in cell lines of B-cell
      origin.
AB  - The carcinoembryonic antigen (CEA) and the classical non-specific cross-reacting
      antigens (NCAs) belong to the CEA gene family which is part of the immunoglobulin
      superfamily. In normal hematopoiesis, CEA gene family members (CGMs) have only
      been reported on cells of myeloid and monocytic origin. In the present study, we
      analyzed 62 childhood acute lymphoblastic leukemias (ALLs) and seven surface
      immunoglobulin positive (sig+) B-cell lines for the expression of the CEA family
      members CEA, NCA-50/90, NCA-95, NCA-160, CGM1 and CGM7. We demonstrated that
      members of the CEA family were present in 76% of childhood ALLs of B- and T-cell
      origin. In ALLs of B-cell origin, 82% of the samples expressed at least one CEA
      subgroup member: 38% NCA-50/90 (CD66c), 31% NCA-160 (CD66a), and 13% both. Six of
      seven B-cell lines solely expressed NCA-160. In seven ALL of T-cell origin, sole
      NCA-160 expression was present in 29% of the cases. CEA and CGM1 were not
      expressed in childhood ALLs or in the sIg+ B-cell lines. In 15 ALLs and seven B
      cell lines which could be analyzed for CGM7 expression, the antigen was not
      detected. NCA-95 was not expressed in 91% of the B-lineage ALLs, in T-lineage
      ALLs and in the B-cell lines. However, five B-lineage ALLs showed conflicting
      data on the binding patterns of two, on leukocytes specifically NCA-95
      recognizing antibodies suggesting either expression of unknown forms of NCA-95 or
      NCA-50/90 or of a yet unknown member of the CEA family in these ALL cells. The
      expression of CEA subgroup members in childhood ALL cells might have prognostic
      impacts, as an inverse correlation exists between NCA expression on leukemic
      blasts and the risk factor white blood count at diagnosis.

PMID- 7808002
TI  - The expression of the Wilms' tumor gene in acute myelocytic leukemias as a
      possible marker for leukemic blast cells.
AB  - The Wilms' tumor gene (wt-1) is expressed in the developing fetal kidney, gonads
      and in Wilms' tumors. Recently, the expression of wt-1 in leukemia-derived cell
      lines and cases of acute leukemias (AL) was reported. The present study was
      designed to investigate the potential of wt-1 as genetic marker for acute
      myelocytic leukemias (AML). Blast cells from 52 patients with AML, 14 patients in
      complete remission (CR) and four leukemic cell lines were examined for expression
      of wt-1 mRNA. Peripheral blood mononuclear cells (PBMNC) and bone marrow (BM)
      from 13 healthy persons were used as negative controls. RNA of the wt-1 gene was
      expressed in 41/52 (79%) patients with previously untreated AML. The majority of
      the 14 patients studied in CR lost wt-1 expression. In three out of the four
      patients in CR reappearance of wt-1 expression preceded relapse of the disease.
      In three of the four tested cell lines wt-1 specific transcription was
      demonstrated. No correlation to FAB classification, immunophenotype or response
      to treatment was found. Our experiments indicate wt-1 expression in the majority
      of AML, but not in bone marrow or PBMNC of healthy controls. Therefore, wt-1
      expression may be associated with the presence of malignant blast cells and the
      analysis of wt-1 gene expression via PCR may be a sensitive method for the
      detection of leukemic blast cells.

PMID- 7808001
TI  - The HLA class I-CML association revisited taking into account the two forms of
      gene fusion in the Philadelphia chromosome. A multicenter study.
AB  - CML patients possess either a b3-a2 or a b2-a2 fusion between the BCR and ABL
      genes. Depending on the type of fusion, two different series of non-self
      potentially immunogenic peptides may be produced. If they are presented by HLA
      class I molecules and recognized by cytotoxic CD8 lymphocytes, individuals could
      be more susceptible or resistant to leukemic cells bearing one or the other form
      of fusion according to their HLA class I phenotype. To test this point, the
      frequencies of HLA-A and HLA-B alleles were compared between b3-a2 and the b2-a2
      CML patients. In essence, no difference was found whose significance could
      withstand correction for multiple comparisons.

PMID- 7808003
TI  - Lymphoid and non-lymphoid tumors in E kappa-myc transgenic rabbits.
AB  - We developed transgenic rabbits with a DNA construct containing the proto
      oncogene c-myc conjugated to the Ig kappa-chain enhancer gene, E kappa. One of
      four transgenic rabbits was mated to a normal rabbit and we used the offspring to
      develop a colony of rabbits carrying the E kappa-myc transgene in their germline.
      Of a total of 19 E kappa-myc transgenic rabbits, eight developed tumors. The
      tumors were characterized histologically and four were diagnosed as lymphoma, and
      one each was diagnosed as embryonic carcinoma, hepatoma, ovarian carcinoma and
      basal cell carcinoma. By Southern analysis, we showed the four lymphomas were of
      B-lymphoid lineage and by nucleotide sequence analysis we found three of them
      most likely used VH1 in their VDJ gene rearrangements. Cells from the embryonic
      carcinoma, the hepatoma and two of the B-lymphomas were adapted to tissue
      culture. We discuss the possibility that tumors of non-lymphoid origin develop in
      the E kappa-myc transgenic rabbits because of the potential for NF-kappa B to
      activate the kappa-enhancer in cells other than B-lymphoid lineage cells.

PMID- 7808004
TI  - Antisense BCR-ABL oligomers cause non-specific inhibition of chronic myeloid
      leukemia cell lines.
AB  - We have examined the effects of antisense oligomers (AOs) of various lengths,
      sequences and chemistry on the proliferation of eight different cell lines, five
      derived from patients with chronic myelogenous leukemia (CML) and three from
      other sources. In general, phosphodiester AOs were inactive, presumably due to
      degradation by nucleases present in fetal calf serum. Both BA2 and B3A2
      phosphorothiolate AOs (but not corresponding sense oligomers) significantly
      inhibited the proliferation of three CML cell lines (BV173, LAMA84, and KYO1),
      but the effect was independent of the type of breakpoint expressed by each cell
      line, suggesting that the inhibition was sequence dependent but not sequence
      specific. The CML cell lines tested showed different sensitivities to inhibition
      of proliferation by AOs--lines with defective expression of the normal ABL
      protooncogene (e.g. BV173) were more readily inhibited than lines with a normal
      ABL message (e.g. K562). We conclude that further studies are necessary to
      delineate the precise mechanism(s) by which CML cell proliferation is inhibited
      by AOs.

PMID- 7808005
TI  - Expression of the multidrug resistance-associated protein (MRP) in acute
      leukaemia.
AB  - A semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) was
      used to investigate and compare transcription levels of the human multidrug
      resistance gene (MDR1) and the recently described multidrug resistance-associated
      protein (MRP) in 105 samples from patients with acute leukaemia at presentation
      and relapse. MRP gene expression was significantly greater in samples from
      patients with acute lymphoblastic leukaemia (ALL) compared with samples from
      normal peripheral mononuclear cells (PBMC) and patients with de novo acute
      myeloid leukaemia (AML). MRP gene expression was found to be higher in patients
      with relapsed de novo AML compared to those at presentation but prior therapy did
      not affect MRP gene expression in ALL. MDR1 gene expression was significantly
      lower in ALL patients compared to normal PBMC and AML samples. Samples from
      patients with secondary AML had higher levels of MDR1 expression than those of de
      novo AML. No changes of MDR1 expression were observed in AML or ALL at relapse.
      No correlation was observed between MDR1 and MRP gene expression in this group of
      patients. Our results suggest that MRP expression may be of prognostic importance
      in AML but the significance of the increased levels we have detected remain
      unclear.

PMID- 7808006
TI  - EVI1 expression associated with a 3q26 anomaly in a leukemia cell line derived
      from the blast crisis of chronic myeloid leukemia.
AB  - Two leukemia cell lines, TS9;22 and YS9;22, were established from different
      individuals with Philadelphia chromosome (Ph)-positive chronic myeloid leukemia
      in blast crisis. The reverse transcript-polymerase chain reaction (RT-PCR)
      technique revealed that both cell lines expressed GATA-1, GATA-2, and the stem
      cell leukemia (SCL) gene, consistent with a megakaryocyte lineage. Chromosome
      analysis revealed that TS9;22 cells show the Ph translocation without abnormality
      of chromosome 3. In contrast, YS9;22 cells show the Ph translocation and
      dic(3)(q26;p12). Northern analysis revealed that YS9;22 cells express the EVI1
      (ecotropic virus integration-1) gene, possibly because of the chromosomal
      translocation in the 3q26 region; TS9;22 cells do not express EVI1. However, no
      rearrangements were detected over 600 kb upstream or over 900 kb downstream of
      EVI1 in the YS9;22 cell line, suggesting a different mechanism of EVI1 activation
      from that in leukemia cells with either a t(3;3)(q21;q26) or inv(3)(q21q26).
      These results indicate that EVI1 expression in YS9;22 cells is linked to the 3q26
      abnormality and that EVI1 activation plays an oncogenic role in the blastic
      transformation of chronic myeloid leukemia.

PMID- 7808007
TI  - Abnormalities in the long arm of chromosome 11 (11q) in patients with de novo and
      secondary acute myelogenous leukemias and myelodysplastic syndromes.
AB  - Leukemias with abnormalities in chromosome 11q23 occur frequently after exposure
      to topoisomerase II-reactive drugs. We investigated the characteristics and
      outcome of patients with de novo or secondary acute myelogenous leukemia (AML) or
      myelodysplastic syndrome (MDS) with abnormalities in chromosome 11q. Sixty-one
      patients had 11q abnormalities. Alterations involved 11q23 in 38 patients and
      other 11q abnormalities in 23. Sixteen patients had secondary disease, 12
      involving 11q23, and four with other 11q abnormalities; 26 patients with de novo
      disease had 11q23 abnormalities and 19 other 11q abnormalities. The most common
      11q23 abnormality was t(9;11), significantly more common in secondary (9/12) than
      in de novo (6/26) leukemias (p = 0.003). There were no significant differences in
      clinical characteristics between de novo and secondary groups involving 11q23.
      Five of 12 patients (42%) with secondary and 20/26 (77%) with de novo disease
      achieved complete remission (p = 0.05). Median survival was 6 weeks in the
      secondary group and 71 weeks in the de novo group (p = 0.001). There were no long
      term survivors in either group. Results are similar when other 11q abnormalities
      are included. Adults with AML or MDS with 11q abnormalities secondary to prior
      chemotherapy have a worse prognosis than patients presenting de novo. However,
      11q abnormalities define a population with a poor prognosis even when presenting
      de novo.

PMID- 7808008
TI  - Bone marrow transplantation from Fv-4-resistant donors rescues Friend leukemia
      virus-infected mice from leukemia: a model of bone marrow transplantation therapy
      against retroviral infection.
AB  - Bone marrow transplantation experiments were conducted in mice in order to
      develop an experimental bone marrow transplantation therapy model, with which to
      investigate possible means to cure retrovirus-infected hosts with bone marrow or
      stem cells from virus-resistant donors. In one experiment, lethally irradiated
      Friend leukemia virus (FLV)-sensitive C3H/He (C3H; Fv-2s, Fv-4s, Rfv-1s, Rfv-2s
      Rfv-3s) mice were transplanted with (i) bone marrow cells from FLV-resistant
      BALB/c-Fv-4Wr (C4W; Fv-2s, Fv-4r, Rfv-1s, Rfv-2s, Rfv-3s) mice (C4W --> C3H) or
      (ii) a mixture of bone marrow cells from C4W and C3H mice (C4W + C3H --> C3H).
      They were then inoculated with FLV 3-4 months later and leukemia development was
      examined. The results indicated that C4W --> C3H chimeras were completely
      resistant to FLV-induced leukemogenesis and that C4W + C3H --> C3H mixed chimeras
      that contained as low as 30% C4W-derived cells, or as high as 70% C3H-derived
      cells, did not develop leukemias. In another experiment, bone marrow cells from
      C57BL/6 (B6; Fv-2r, Fv-4s, Rfv-1r, Rfv-2r, Rfv-3r) or C4W donors were grated to
      FLV-sensitive DBA/2 mice (DBA; Fv-2s, Fv-4s, Rfv-1s, Rfv-2s, Rfv-3s) that had
      been infected with FLV 6 days earlier (DBA-FLV). The results indicated that most,
      if not all, FLV-infected DBA mice which received bone marrow transplantation from
      B6 donors developed B6-derived leukemias, although the survival time of these
      mice was dramatically prolonged as compared to that of untreated DBA-FLV mice. In
      contrast, bone marrow transplantation from Fv-4r-bearing C4W donors successfully
      rescued FLV-infected DBA mice from leukemic deaths. Thus, the bone marrow
      transplantation therapy against retroviral infection of hemopoietic cells was
      shown to be feasible, provided that donor cells carry a resistant allele that
      functions via receptor blockade as in the case of Fv-4r, but less effective when
      the roles of the resistant alleles partially interfered with the virus
      replication, leukemic transformation and/or cycling of target cells as suggested
      for Fv-2r gene action, or to resist virus infection by immunological means as are
      known for Rfv-1r, Rfv-2r and Rfv-3r genes which are also carried by B6-strain
      mice. Implication of these findings on the somatic gene therapy against
      retrovirus infection diseases in man are discussed.

PMID- 7808009
TI  - Verapamil inhibits B-cell proliferation and tumor necrosis factor release and
      induces a clinical response in B-cell chronic lymphocytic leukemia.
AB  - Four B-CLL patients, treated with verapamil for cardiac problems, showed
      substantial reduction of lymphadenopathy in one, a 3- and 5-year stabilization of
      B-CLL in two patients, and a dramatic decrease in lymphocyte count,
      lymphadenopathy and splenomegaly in one stage IV patient. We therefore studied
      the effects of verapamil on B-CLL cells in vitro. In 13 samples we observed that
      verapamil strongly inhibited in vitro proliferation of pokeweed mitogen (PWM)
      stimulated and unstimulated cells. Using a cytotoxic bioassay, we found that
      verapamil markedly inhibited the spontaneous and PMW-induced release of tumor
      necrosis factor (TNF) by B-CLL cells. These findings suggest that verapamil may
      block B-CLL cell proliferation through inhibition of TNF release and thereby may
      contribute to the management of B-CLL.

PMID- 7808010
TI  - Giant parallel tube arrays (PTAs), a new type of lymphocyte inclusion.
AB  - In a 56-year-old male patient, receiving chemotherapy after radical surgery for
      bladder carcinoma, an unusual type of cytoplasmic inclusion was discovered in
      about 30% of peripheral blood lymphocytes. This was a single, large (about 2
      microns in diameter), round or ovoid body, darker than the nucleus and reddish
      violet in May-Grunwald-Giemsa stain. The examination with transmission electron
      microscope demonstrated that such inclusions were made up of giant parallel tube
      arrays (PTAs). The absolute lymphocyte count was normal, but there was an
      expansion of CD3+, CD4-, CD8+, CD11b, TCR alpha beta lymphocytes. The lymphocytes
      bearing the inclusion were CD3+ and CD8+. DNA studies suggested an expansion of T
      cell population with clonal rearrangement of TCR beta and TCR gamma. This case
      can be classified as an asymptomatic disorder of large granular lymphocytes, with
      unusual morphology. Giant PTAs should be taken into account in the differential
      diagnosis of lymphocyte cytoplasmic inclusions.

PMID- 7808011
TI  - Distinct MLL gene rearrangements associated with successive acute monocytic and
      lymphoblastic leukemias in the same patient.
AB  - A patient with acute monocytic leukemia (AMoL) and t(6;11)(q27;q23) developed
      acute lymphoblastic leukemia (ALL) and t(4;11)(q21;23), 10 months after complete
      remission of the AMoL. The MLL gene, normally located at band 11q23, appeared
      differently rearranged in the cells of these two leukemias, showing a different
      origin for the two malignant clones. The responsibility of etoposide, used in
      treatment of the AML, in the occurrence of the ALL is probable in this patient.

PMID- 7808012
TI  - Detection of immunoglobulin kappa light-chain gene rearrangement patterns by
      Southern blot analysis.
AB  - Immunoglobulin light-chain (IgL) gene rearrangements occur in a sequential order
      during normal B-cell differentiation with Ig kappa gene rearrangements prior to
      Ig lambda gene rearrangements. Therefore, Ig kappa producing B-cells usually
      retain Ig lambda genes in germline configuration, whereas the Ig kappa genes are
      generally deleted on one or both alleles in most Ig lambda producing B-cells. The
      deletion processes in the Ig kappa locus are mediated via rearrangement of the
      kappa deleting element (Kde), which is located approximately 24 kb downstream of
      the constant (C) kappa gene segment. Kde rearrangements can delete the C kappa
      region (including the Ig kappa enhancer) or the complete joining (J) kappa-C
      kappa region via rearrangements to a heptamer recombination signal sequence in
      the J kappa-C kappa intron (intron RSS), or via rearrangement to a variable (V)
      kappa gene segment, respectively. To improve the Southern blot detection of
      clonal Ig kappa gene rearrangements and deletions in B-lineage malignancies, we
      developed a new set of optimal J kappa, C kappa, and Kde probes, and made a
      detailed restriction map of the J kappa, C kappa, and Kde region. Extensive
      Southern blot studies revealed that rearrangements in the J kappa gene region are
      optimally detectable by use of a J kappa probe in combination with at least two
      appropriate restriction enzymes, i.e. BamHI, BglII, EcoRI, HindIII, and/or SacI.
      J kappa gene rearrangements are also detectable with the C kappa probe in BglII
      and BamHI digests, if no deletion of the C kappa region has occurred. The two
      different types of Kde-mediated J kappa and/or C kappa gene deletions are easily
      detectable with the Kde probe in BglII, HindIII and/or EcoRI digests. This is in
      contrast to the inaccurate information obtained with the J kappa and C kappa
      probes, because these probes can detect deletions only in the form of decreased
      densities of J kappa and/or C kappa germline bands in the absence of rearranged
      bands. Our detailed analysis of 217 B-lineage leukemias revealed that 62%
      (69/111) of precursor B-cell acute lymphoblastic leukemias had rearranged and/or
      deleted Ig kappa genes. All 53 Ig lambda+ chronic B-cell leukemias contained Ig
      kappa gene deletions; in 75% this concerned biallelic J kappa and/or C kappa gene
      deletions. Virtually all Ig kappa gene deletions appeared to be mediated via Kde
      rearrangements, while only 1.5% of the Ig kappa gene deletions were mediated via
      an alternative deletion mechanism which involved the J kappa region.

PMID- 7808013
TI  - Trisomy 11 in acute myeloid leukemia: ten cases.

PMID- 7808014
TI  - Inactivation of the p53 gene in leukemias and myelodysplastic syndrome (MDS) with
      17p monosomy.

PMID- 7808015
TI  - Molecular elimination of Ph1 clone in a chronic myelogenous leukemia patient with
      interferon-alpha alone.

PMID- 7808016
TI  - Incidence and clinic-pathologic features of non-Hodgkin lymphoma in a cohort of
      human immunodeficiency virus positive coagulopathic patients.

PMID- 7808017
TI  - The retinoid receptors.
AB  - The retinoid receptors belong to a large superfamily of ligand-inducible
      transcription factors that include the steroid, vitamin D and thyroid hormone
      receptors, the peroxisome proliferator-activated receptor, the insect edysteroid
      receptor, and a number of orphan receptors whose ligands are unknown. All nuclear
      receptors have several well-characterized structural domains, including a
      conserved DNA-binding domain, and a ligand binding domain at the carboxyl
      terminus of the receptor. The RAR and RXR classes of nuclear retinoic acid
      receptors are each composed of alpha, beta and gamma subtypes with more than one
      isoform for each receptor subtype. Data from many investigators suggest there are
      RAR- and RXR-dependent gene pathways, and that the individual receptor subtypes
      may control distinct gene expression patterns. In addition, RXR has been found to
      heterodimerize with other nuclear receptors to form active transcriptional
      complexes, which influence the activity of a variety of gene pathways important
      in growth and differentiation. As a result, retinoids have been useful clinical
      agents in Dermatology and Oncology. However, upon prolonged exposure to retinoic
      acid, resistance to retinoids has often been encountered both in the clinical
      setting and in long-term cell culture (HL60R and RAC65 cells). In the latter
      case, retinoid resistance has been associated with a mutation in the RAR gene
      which transcribes a RAR receptor truncated at the C-terminal end. These mutated
      RAR receptors exhibit a reduced affinity for retinoic acid while retaining the
      ability to bind to a retinoic acid response element on DNA. As a result, these
      mutant receptors exhibit dominant-negative activity by binding to the DNA without
      activating transcription and by competing with other receptors for sites on the
      response element. In fact, dominant-negative activity may be very important in
      the development of many neoplastic diseases, including acute promyelocytic
      leukemia (APL), where a t(15;17) chromosomal translocation fuses the PML gene to
      the RAR gene, to produce a PML-RAR fusion protein in large excess in the cell.
      However, retinoid resistance in the patient is most probably the result of
      pharmacokinetic problems, whereby, with continuous retinoid treatment, the plasma
      levels of retinoic acid gradually decrease to below that required to maintain
      differentiation of leukemic cells in vivo. A major challenge for drug discovery
      is to design a drug which circumvents these pharmacokinetic problems either by
      designing novel drug delivery systems or by employing retinoids which do not bind
      to CRABP, such as 9-c-RA.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7808018
TI  - Proceedings of the 2nd Workshop on Retinoids in Oncology. London, United Kingdom,
      January 21-22, 1994.

PMID- 7808019
TI  - Clinical pharmacology of all-trans retinoic acid.
AB  - The clinical pharmacology of all-trans retinoic acid (RA) has distinct
      differences from that of its widely studied stereoisomer 13-cis retinoic acid
      (cRA). RA is much more rapidly cleared from plasma following oral administration;
      their respective half-lives are < 1 h and 13 h. There is extensive accumulation
      of the 4-oxo-cRA in plasma following repeated doses of cRA, while 4-oxo-RA is
      only a minor metabolite in plasma following RA administration. The extent of
      isomerization in vivo differs for the two retinoids. In contrast to cRA, where up
      to a 1:3 ratio of RA to cRA is observed in patient plasma following drug
      administration, cRA concentrations in excess of 10 ng/ml are rarely observed in
      plasma of patients receiving exogenous RA. RA administration produces
      autoinduction of its own oxidative catabolism; this effect does not occur with
      cRA. These pharmacokinetic differences have been observed in leukemia and solid
      tumor patients. Detailed analysis of the results of the population studied
      suggest that both constitutive and RA-induced hypercatabolism of RA occurs. Both
      of these hypercatabolic states can be modulated by concurrent administration of
      ketoconazole, an inhibitor of cytochrome P-450 and lipoxygenase-mediated
      oxidations.

PMID- 7808020
TI  - Clinical and pharmacokinetic studies of all-trans-retinoic acid in pediatric
      patients with cancer.
AB  - This review will summarize the rationale for pursuing investigations into the use
      of retinoids for pediatric patients with cancer, describe the phase I results of
      all-trans-retinoic acid (ATRA) in children, and discuss the results of a series
      of preclinical and clinical pharmacokinetic studies of ATRA. The prognosis for
      children with advanced stage neuroblastoma, the most common extracranial solid
      tumor of childhood, has remained poor despite significant increases in the
      intensity of multi-modality therapy. Observations that neuroblastoma has the
      potential in vivo to differentiate into the more mature neuronal phenotype of a
      ganglioneuroma or to spontaneously regress, combined with the ability of ATRA to
      induce differentiation of neuroblastoma cell lines in vitro, suggests that
      neuroblastoma may be a prime candidate for a retinoid-based approach to
      differentiation therapy. We previously performed a standard pediatric phase I
      trial of ATRA and defined the maximum tolerated dose (MTD) in children to be 60
      mg/m2/day, significantly lower than the MTD in adult patients. Pharmacokinetic
      results revealed that the plasma half-life of ATRA was short (45 min) relative to
      13-cis-RA (12-24 h), and that plasma drug exposure decreased significantly by day
      28 of daily drug administration. Preclinical studies using an i.v. formulation of
      ATRA in a Rhesus monkey pharmacokinetic model then demonstrated that ATRA is
      eliminated by a capacity-limited (saturable) process. This elimination process
      was rapidly induced within the first week of daily i.v. ATRA administration, and
      suggested that an intermittent schedule of drug administration might allow for
      down-regulation of the elimination process. These pre-clinical studies formed the
      basis for investigating whether an intermittent schedule of ATRA administration
      would allow for repeated periods of relatively higher plasma drug concentrations.
      Preliminary results of two clinical trials using intermittent schedules of
      administration suggest that this approach may result in significantly higher
      plasma drug exposure over time. Plans to study the role of intermittent schedules
      of ATRA administration in pediatric phase II trials in patients with
      neuroblastoma are underway.

PMID- 7808021
TI  - All-trans retinoic acid for the treatment of AIDS-related Kaposi's sarcoma:
      results of a pilot phase II study.
AB  - Retinoids have anti-tumor activity in several malignant and premalignant
      conditions. Since Kaposi's sarcoma is regulated by steroid hormones both in vivo
      and in vitro, we hypothesized that retinoids may have anti-tumor effects in AIDS
      related Kaposi's sarcoma. Thus, 27 patients with mucocutaneous, non-visceral AIDS
      related Kaposi's sarcoma were treated with all-trans retinoic acid (tRA). Poor
      tolerance was observed at the initial starting dose of 150 mg/m2, and thus
      subsequent patients were treated using a weekly dose escalation, starting with 45
      mg/m2 (given daily, in subdivided doses), to the target dose of 150 mg/m2 (given
      daily in three subdivided doses). Nearly half (46%) of the patients had extensive
      mucocutaneous disease with over 25 lesions. No patient had received prior
      cytotoxic chemotherapy. Ten patients had CD4 lymphocytes of 200/mm3 or greater
      (strata I); and 17 had under 200/mm3 CD4 lymphocytes (strata II). The median of
      the average daily tRA dose administered was 150 mg (90 mg/m2; there was no
      significant difference in the dose tolerance between the two strata). Adverse
      effects consisted of transient mild to moderate headaches in 65% of patients,
      mild to moderate skin dryness and cheilitis in 61%, and nausea and vomiting in
      31%. Hematologic toxicities included hypertriglyceridemia in 62%, anemia in 23%,
      and neutropenia in 23%. Partial response to therapy was observed in 4/24 (17%)
      evaluable patients, occurring after 12, 20, 24, and 28 weeks of therapy, and
      lasting 4-24 weeks. Three responders had baseline CD4 lymphocyte counts <
      200/mm3. Three additional patients experienced reduction in measured indicator
      lesions of greater than 25% but less than 50%, and seven patients experienced
      disease stabilization of 16 weeks or greater. In evaluable patients, the median
      time to disease progression was 22 weeks and the overall median survival in all
      patients was 27.3 months. No significant changes in CD4 lymphocyte counts, p24
      antigen, and beta 2 microglobulin were observed over time. However, a
      statistically significant increase was observed in soluble IL-2 receptor levels
      while on tRA (p = 0.037). We conclude that tRA has activity in patients with
      mucocutaneous AIDS-related Kaposi's sarcoma with acceptable toxicity. tRA has
      immunological effects without upregulation of HIV parameters. Additional studies
      in combinations or with more active retinoids are warranted.

PMID- 7808022
TI  - Evolution of aerodigestive tract 13-cis-retinoid acid chemoprevention: the M.D.
      Anderson experience.
AB  - The ultimate goal of our chemoprevention research is to prevent or inhibit the
      development of aerodigestive cancer in humans. We have made substantial progress
      from our trials 10 years ago. The chemopreventive strategies utilized in our
      clinical trials involve the use of retinoids and carotenoids as chemopreventive
      agents. The choice of these agents was based upon their important
      anticarcinogenic and differentiation properties. It is important to understand
      how retinoids interact with cells to carry out their modulating activities, and
      we hope to increase our understanding through molecular analysis of retinoid
      receptors. In the case of aerodigestive epithelial tissues at risk, normal, non
      keratinizing epithelial cells often express inappropriate squamous
      differentiation. Retinoids are thought to suppress premalignant lesions by
      suppressing these inappropriate squamous differentiation pathways. The role of
      retinoids in suppressing squamous differentiation markers and reversing
      premalignant lesions will be elucidated from this retinoid project. The
      development of a fundamental understanding of tumorigenesis in the aerodigestive
      tract can lead to novel preventive approaches. A relative degree of risk for
      cancer development in individuals depends on several components, including the
      extent of carcinogenic exposure, inherent sensitivity of the individual to
      carcinogens, the individual's nutritional status, etc. Individuals with a genetic
      component of increased carcinogen sensitivity appear to be at increased risk for
      developing primary and secondary tumors. Our chemoprevention research program is
      designed to develop innovative strategies for aerodigestive tract epithelial
      cancer prevention. The strength of our program is to bridge the gap between
      fundamental and cellular molecular studies in clinical chemoprevention trials.
      The outcome of our research efforts may have an enormous impact on public health
      in controlling aerodigestive epithelial cancers and other epithelial cancers as
      well.

PMID- 7808023
TI  - Combination 13-cis-retinoic acid and interferon alpha-2a in the therapy of solid
      tumors.
AB  - Preclinical data indicate that the combination of retinoids and interferons have
      synergistic antiproliferative and differentiating effects in some hematologic and
      solid tumor models. These observations have led to clinical trials in which 13
      cis-retinoic acid (13cRA) 1 mg/kg/day was combined with interferon alpha-2a (IFN
      alpha) 3 or 6 x 10(6) U/day. The first two such trials produced exciting results:
      50% response rate in patients with previously untreated stages IB-IVA cervix
      cancer and 68% in patients with advanced squamous cell skin cancer. These data
      led to a number of additional trials of the combination, but the high response
      rates seen in the initial cervix and skin trials have not been duplicated in the
      other squamous tumors tested (head and neck, lung, pretreated cervix). In
      addition, trials in two nonsquamous histologies were negative (lung and
      melanoma). However, the regimen was not always studied in an optimal population
      of previously untreated patients and the negative results in pretreated cervix
      patients point to the relevance of this consideration. Nevertheless, the
      observation that the combination of 13cRA and IFN alpha (both of which bind to
      specific receptors and change gene expression) is able to induce regression in
      advanced tumors, must be regarded as highly important. Key questions to be
      addressed include an understanding of the biologic mechanism of specific tumor
      sensitivity (why some squamous tumors and not others?), and mechanisms of
      resistance in sensitive tumor types (e.g. cervix). Such data may lead to trials
      targeted to tumor types with defined biologic features having a high liklihood of
      clinical benefit. In the meantime, studies integrating this combination with
      other active treatment modalities such as radiation is warranted in cervix and
      skin carcinomas.

PMID- 7808024
TI  - The arotinoids: early clinical experience and discussion of future development.
AB  - There has been great interest in the use of drugs attempting to modify the
      properties of malignant cells without necessarily destroying them. The family of
      compounds known as the retinoids have shown particular promise in this area.
      Current interest is directed towards established retinoids such as ATRA and 13
      CRA. Newer synthetic retinoids such as fenretinide, the arotinoid Ro 40-8757, and
      9-cis retinoic acid have been entering clinical trials. Ro 40-8757 is a
      particularly interesting new arotinoid with properties quite distinct from the
      other retinoids. It has different binding proteins and appears to regulate
      different genes than the classical retinoids such as ATRA or 13-CRA. Furthermore,
      it appears active against a different spectrum of malignancies. It also appears
      to have a relatively favourable side-effect profile. In addition to its anti
      proliferative effects, this arotinoid may play a role in protection of bone
      marrow function after use of cytotoxic drugs. Development of Ro 40-8757 was
      halted before the compound had entered phase II testing due to lack of resources.
      Future developmental programmes for retinoids should move rapidly to explore the
      potential of interesting combinations identified in preclinical models. Retinoids
      should be considered primarily as drugs which modulate and enhance the effects of
      other active anticancer agents. Their development should not be prevented because
      they are unlikely to be active as single agents against common solid tumours.

PMID- 7808025
TI  - Retinoids in bladder, testis and prostate cancer: epidemiologic, pre-clinical and
      clinical observations.
AB  - Genitourinary cancers--bladders, testis and prostate--account for almost 50,000
      deaths per year. Epidemiologic data suggest that individuals with low serum
      retinoid levels or low dietary intake of retinoid-containing foodstuffs have an
      increased risk of bladder and prostate cancer. Preclinical investigations show
      that a variety of retinoids suppress the proliferation of prostate and bladder
      cancer cells and induce differentiation in teratocarcinoma cells. Retinoids
      prevent the emergence of murine bladder and prostate cancers in carcinogen
      treated animals. Clinical data are disappointing or inconclusive. A single well
      conducted phase 2 trial of 13-cis retinoic acid in patients with germ cell tumors
      was negative. Several historically controlled as well as prospectively
      randomized, placebo-controlled trials of retinoids in superficial bladder cancer
      have failed to provide evidence of the efficacy of retinoids. Two studies of all
      trans-retinoic acid in advanced prostate cancer have been negative. Despite
      compelling preclinical rationale, retinoids have failed to yield positive results
      in the clinical management of prostate, bladder or testis cancers. Further work
      is needed to define subsets of patients in whom retinoids might be active, and
      whether new retinoids or new approaches to retinoid delivery will improve the
      clinical usefulness of retinoids in these tumors.

PMID- 7808027
TI  - Breast cancer and fenretinide, an analogue of vitamin A.
AB  - Preclinical studies make fenretinide attractive for prevention and treatment of
      breast cancer. It inhibits mammary gland end bud formation in developing animals.
      Carcinogen-induced mammary cancer is suppressed by fenretinide, both at early and
      late stages of carcinogenesis, in young and mature rats. Fenretinide causes
      regression of invasive rat mammary cancer. Cytostatic activity has been
      demonstrated against human breast cancer cell lines. Autocrine stimulation of
      human breast cancer cell lines by tgf-alpha, insulin-like growth factors I and II
      is significantly abrogated by fenretinide. The human half-life is 24 hours.
      Absorption is markedly affected by meal content. Serum levels of 1 mM are
      achieved at doses of 200 mg/day. This dose significantly suppresses serum IGF-I
      levels in women. This concentration is capable of suppressing human breast cancer
      growth in vitro. A 3-day drug holiday is given each month in order to restore
      serum retinol levels. Under these circumstances, fenretinide is well tolerated. A
      phase III trial evaluating the efficacy of fenretinide for breast cancer
      prevention in high-risk women has been completed. Tamoxifen enhances the
      effectiveness of fenretinide in carcinogenesis models. The combination can be
      safely administered to women. A phase III adjuvant trial of tamoxifen, with or
      without fenretinide will be conducted in the United States.

PMID- 7808026
TI  - First hints in non-small cell lung cancer (NSCLC).
AB  - All-trans retinoic acid was evaluated in metastatic measurable non-small cell
      lung cancer. All-trans retinoic acid was given at 175 mg/m2 orally on a daily
      basis. Twenty-eight patients (median age 58, 16 males, 12 women) had an ECOG
      performance status of 0 (26 patients) and 1 (two patients). Sixteen of the 28 had
      no weight loss. Eleven had between 5 and 10% and only one had greater than 10%
      weight loss at time of entry. Toxicities included cutaneous (cheletis 25/28),
      fatigue (10/28), myalgias/anthralgias (9/28), and headache (17/28). Alterations
      in triglycerides and hepatic transaminases were noted in a majority of patients.
      Two partial responses occurred in patients with adenocarcinoma. Both responses
      were 7 months in duration. Activity of all-trans retinoic acid in metastatic non
      small cell lung cancer is minimal, but due to its low toxicity profile it should
      be tested in setting with other agents.

PMID- 7808028
TI  - All-trans retinoic acid therapy in relapsed/refractory or newly diagnosed acute
      promyelocytic leukemia (APL) in Japan.
AB  - We have conducted four prospective multicenter studies for acute promyelocytic
      leukemia (APL) using oral 45 mg/m2 all-trans retinoic acid (ATRA) daily. The
      first three studies were for relapsed/refractory APL, and the fourth study for
      newly diagnosed APL. In the first study with ATRA alone, 18 (82%) of 22 evaluable
      patients achieved complete remission (CR). Initial peripheral leukemia cell
      counts were significantly less in the CR cases (p < 0.01); < 100/microliters in
      17 of 18 CR cases, and > or = 200/microliters in all failure cases. In the second
      study, if initial leukemia cell counts were more than 200/microliters,
      chemotherapy with daunorubicin and behenoyl cytarabine was first given, and then
      ATRA was started. Of 42 evaluable patients, 36 (86%) achieved CR. In the third
      study, if initial leukemia cell counts were more than 200/microliters,
      chemotherapy was concomitantly given with ATRA, and if during the ATRA therapy
      leukemia cell counts became more than 1000/microliters, chemotherapy was added.
      Of 46 evaluable patients, 36 (78%) achieved CR. Patients achieving CR received
      standard consolidation and maintenance chemotherapy, and the 29-month predicted
      disease-free survival (DFS) rate is 72% for 41 cases achieving their first CR
      with ATRA, and 20% for 49 cases achieving their second CR with ATRA. In the
      fourth study for newly diagnosed APL, if leukocyte counts were more than
      3000/microliters, chemotherapy was concomitantly given with ATRA, and if during
      the ATRA therapy leukemia cell counts became more than 1000/microliters,
      chemotherapy was added. Of 109 evaluable patients, 97 (89%) achieved CR, and the
      19-month predicted event-free survival rate for all patients is 78%, and the DFS
      rate is 88% for 97 cases achieving CR. ATRA produces a high CR rate in both
      relapsed/refractory and newly diagnosed APL, and should be incorporated in the
      first-line therapy of this disease.

PMID- 7808030
TI  - Induction treatment of acute promyelocytic leukemia using all-trans retinoic
      acid. Controversies about dosage, advantages and side-effect management.
AB  - All-trans retinoic acid (ATRA) in acute promyelocytic leukemia (APL) represents
      the leading example of targetted drugs for inducing an in vivo differentiation of
      malignancy (1,2). A fixed dose of 45 mg/m2/day was proposed for the treatment of
      patients (3), according to the results obtained by retinoic acid derivatives in
      skin diseases. We report that 25 mg (4), and even 15 mg/m2/day are still
      effective dosages. Absence of drug resistance, rapid correction of
      fibrinogenopenia and the absence of hypoplasia are the apparent major advantages
      and consequently high frequency of early mortality generally reported during
      chemotherapy is expected to be reduced. In fact the same risk of early death
      (10%) is recorded in all available data (5), due to coagulation disorders and to
      a leukocyte activation syndrome. Management of these side-effects is based on the
      prevention and treatment of the irreversible state as soon as first symptoms
      appear. Actually the major advantage of ATRA treatment in addition to
      chemotherapy is the decrease of relapse rate (6), the increase of event-free
      survival, and thus the increase of survival.

PMID- 7808029
TI  - Results of APL 91 European trial combining ATRA and chemotherapy: presentation of
      APL 1993 trial.
AB  - Initial results of ATRA in newly diagnosed APL showed that this drug was
      associated with a high complete remission (CR) rate but also (i) to a risk of
      hyperleukocytosis and of ATRA syndrome, (ii) to rapid relapse unless ATRA was
      followed by intensive chemotherapy. These findings prompted our group to design
      an approach combining ATRA and intensive chemotherapy in newly diagnosed APL,
      where chemotherapy could prevent relapses and also, in cases with increasing
      leukocyte counts, could prevent the ATRA syndrome. In a pilot study, this
      approach gave a high CR rate (96%) and (with now prolonged follow-up) a
      significant reduction in the incidence of relapse, as compared to a historical
      control treated with chemotherapy alone. The superiority of the combination of
      ATRA and chemotherapy over chemotherapy alone (especially for the incidence of
      relapse) was subsequently confirmed in a randomized European trial (APL 91
      trial). We are now testing in a new European trial (APL 93 trial) whether
      chemotherapy should be administered with ATRA, or should follow ATRA during
      induction treatment, and whether maintenance therapy with intermittent ATRA, low
      dose chemotherapy, or both can further reduce the risk of relapse.

PMID- 7808031
TI  - Synopsis of the discussions of the workshop: hematology.

PMID- 7808032
TI  - Synopsis of workshop: hematology 1.

PMID- 7808033
TI  - Solid tumor treatment workshop summary.
AB  - Retinoic acids exert a wide range of biological activities following binding to
      the cognate nuclear receptors, which has several members (RAR-alpha, beta, gamma
      and RXR-alpha, beta, gamma). Retinoic acids lead to several different effects on
      tumor cells and include cell differentiation, inhibition of cell proliferation
      and apoptosis. The expression and abundance of each receptor type, and the
      distinct role of each receptor type related to biologic effect is under
      investigation. Similarly the mechanism(s) responsible for favorable responses in
      certain tumor types (skin, cervical) needs to be understood to best utilize this
      family of compounds, either alone or in various combinations. The significancer
      of drug-drug interaction in regard to their effects on pharmacokinetics, receptor
      modulation and regulation of cytoplasmic retinoic acid receptor binding proteins
      (CRABPs) should be carefully evaluated in pre-clinical and clinical trials.
      Furthermore, appropriate models to study combinations of RAs with other
      biological response modifiers are needed.

PMID- 7808034
TI  - Synopsis of workshop on treatment of solid tumours.
AB  - A workshop was held which attempted to identify the clinical trials that need to
      be performed using retinoids alone or in combination in patients with solid
      tumours. 13-cis retinoic acid is currently the preferred retinoid apart from in
      breast cancer where hydroxy phenyl retinamide might be preferable. It was agreed
      that standard response criteria should be used in phase II trials but that
      response rates as low as 5% should be sufficient to encourage randomized adjuvant
      or maintenance trials where survival would be the main endpoint.

PMID- 7808035
TI  - Solid tumours--chemoprevention with retinoids.
AB  - There is a clear change in the treatment strategies for solid tumours towards the
      treatment of early rather than advanced disease. Retinoids represent a
      potentially useful class of drugs in chemoprevention. Preclinical data and
      clinical experience suggests that different retinoids may have different spectra
      of antitumour activity and synergistic interactions between retinoids and
      cytokines have also been reported. 13-cis retinoic acid has shown some promising
      activity in preventing the onset of second primary tumours in head and neck
      cancer and fenretinide is being tested in the prevention of second primary breast
      cancers. An understanding of the role of the different retinoid receptors could
      lead to the design of compounds with a better therapeutic index. Despite these
      early indications that retinoids could be useful in this area, the development of
      such drugs is far from easy. Appropriate study designs for screening
      differentiating agents in the clinic, and the relevance of preclinical models of
      chemoprevention are challenges to be addressed. Unresolved issues include optimal
      patient selection, long clinical trial times, optimal dose, schedule and
      treatment duration. The use of biological surrogate markers for longer time
      dependent trial endpoints could significantly contribute to more rapid
      development. Ongoing clinical studies, particularly in tobacco-related diseases,
      will better define the role of retinoids in this clinical setting. Clinicians
      should be encouraged to enter patients into large well organized clinical
      studies.

PMID- 7808036
TI  - Long-term consequences of surgical treatment of peptic ulcer.
AB  - Surgical treatment of peptic ulcer may lead to several late postoperative
      morphological and metabolic abnormalities. Forty two patients (16 females and 26
      males) at mean age of 47 years after surgery for peptic ulcer (mean postoperative
      period of 9 years) were recruited in this study. Following methods have been used
      for evaluation of those patients: clinical and serum biochemical assessment, UGI
      tract endoscopy, histology of gastric or duodenal mucosa biopsies, test for H
      pylori presence, Ca-P-Mg homeostasis and BMD using DXA-absorptiometry. No
      clinical and biochemical abnormalities were found. In 60% of examined pts
      gastritis or duodenitis with various degrees of the reflux were found
      endoscopicaly. In 64% of pts histology showed signs of mucosal inflammation.
      Recurrent ulcer was found in 3 pts. H-pylori was present in 16 pts (40%). The
      significant reduction of BMD, especially of the lumbar spine, in the pts after
      the PG resection in comparison to the pts with the vagotomy was found. Within
      several years after gastric operation the patient must be carefully evaluated and
      adequate supplementation of Ca and vitamin D is strongly recommended.

PMID- 7808037
TI  - Accumulation of ammonia and changes in the activity of some ammonia metabolizing
      enzymes during brain ischemia/reperfusion injury in rats.
AB  - The ammonia concentration and changes in the activity of ammonia metabolizing
      enzymes in the brain tissue during ischemia/reperfusion were investigated in
      rats. During ischemia (0.5 h) we found a statistically significant increase in
      brain ammonia concentration and a significant decrease in glutamate dehydrogenase
      activity. After 1 h of reperfusion, a further accumulation of ammonia
      concentration was observed. Furthermore, the brain glutamine syntethase and
      glutamate dehydrogenase were decreased, whereas the brain glutaminase activity
      was increased. The causes for the changed activities of some ammonia metabolizing
      enzymes in brain after ischemia/reperfusion have been discussed.

PMID- 7808038
TI  - The effects of sodium valproate and its metabolites (5-OH-VPA and 4-OH-VPA) on
      electroconvulsions in rats.
AB  - Effects of sodium valproate (VPA) and the omega-oxidation metabolites (5-OH-VPA
      and 4-OH-VPA) on the electroconvulsions in rats were analyzed. The drug (100 and
      200 mg/kg/day) revealed marked dose-related anticonvulsant effect which
      manifested themselves by shortening the convulsions time and their intensity. The
      anticonvulsant effect of the omega-oxidation (50, 100 and 200 mg/kg/day) were
      weaker compared with the parent drugs.

PMID- 7808039
TI  - Mineralization (calcification) of coronary arteries.
AB  - Mineralogical investigations of calcifications located in coronary vessels were
      performed on the material obtained from the endarterectomized arteries of 18
      patients (15 M, 3 F, aged 36-65) during surgical revascularization procedures
      consisting in coronary artery bypass grafting. The samples were tested using
      scanning microscopy, X-ray diffractometry, infrared spectroscopy, atomic
      absorption spectroscopy, electron microprobe and neutron activation spectroscopy.
      The results of analyses were calculated with the use of computer programmes. Two
      types of mineralization were determined: 1. secret mineralization identified as
      higher than normal content of elements in biological tissues, not demonstrating
      any mineral grains, and 2. apparent mineralization, appearing micro- and
      macroscopically as grains composed mainly of hydroxyapatite containing admixture
      of carbonate groups, i.e. a mineral identical with apatite present in bones, or
      as calcification of other tissues (heart valves, lungs etc.). The authors suggest
      that the phenomenon of mineralization should be taken into consideration in the
      preventive treatment of coronary atheriosclerosis.

PMID- 7808040
TI  - Activation of blood coagulation induced by organophosphate pesticide.
AB  - A case of suicidal poisoning with organophosphate pesticide, associated by acute
      activation of blood coagulation is presented. The heparin treatment efficiently
      inhibited this activation.

PMID- 7808041
TI  - Association of ganglioneuroblastoma with horse-shoe kidney.

PMID- 7808042
TI  - Observations on gastric histology, endoscopy appearance and Helicobacter pylori
      after corrective surgery for bile reflux gastritis.
AB  - This study was designed to look for the presence of Campylobacter pylori in
      patients who had Roux-en-Y procedure to control symptoms of severe alkaline
      reflux gastritis (ARG) and to correlate findings with endoscopy and histology.
      Twenty five patients, who had been operated on for ARG during the last 15 years,
      were recruited into this study (mean age: 53 years). Surgical procedures were
      performed by a single surgeon (K.B.). Clinical symptoms of ARG improved after
      corrective surgery in all cases, but endoscopic pictures remained abnormal in 14
      of 25 patients and histological gastritis was observed in all cases. Helicobacter
      pylori were detected in 8 patients using an urease test performed on gastric
      mucosa biopsies (CLO-Gistbrocades test). All 8 patients had their biliary
      diversion 10 or more years earlier, suggesting that H-pylori colonisation of the
      gastric mucosa develops only slowly once the bile reflux has been stopped.
      Longitudinal studies, looking for the presence of H-pylori in postoperative
      stomachs, may help in determining whether they have a role in the aethiology of
      the peptic ulcer and gastritis, or whether it really is only an innocent
      bystander.

PMID- 7808043
TI  - Malignant catatonia or nonconvulsive status epilepticus?

PMID- 7808044
TI  - Treatment of patients with one- or two-vessel coronary artery disease.

PMID- 7808045
TI  - Mortality associated with transesophageal echocardiography.

PMID- 7808046
TI  - Stress echocardiography. Part II. Dobutamine stress echocardiography: techniques,
      implementation, clinical applications, and correlations.
AB  - OBJECTIVE: To describe the rationale, methods, and clinical applications for
      dobutamine stress echocardiography. DESIGN: We review our experience with the
      first 1,000 Mayo Clinic patients who underwent this procedure and discuss studies
      from the literature that have assessed the accuracy of dobutamine stress
      echocardiography in determining the presence and extent of coronary artery
      disease. MATERIAL AND METHODS: The Mayo protocol for dobutamine stress
      echocardiography is presented, and the indications for use of this test and
      comparisons of sensitivity and specificity with other tests are summarized.
      RESULTS: Although exercise stress testing is the usual noninvasive method for the
      detection and assessment of coronary artery disease, a substantial number of
      patients are unable to perform adequate exercise because of physical limitations.
      In these patients, dobutamine stress echocardiography has emerged as a feasible,
      safe, and accurate method for the evaluation of coronary artery disease. The test
      has been proved to be valuable in the noninvasive diagnosis of coronary artery
      disease and to have an accuracy comparable to that of tomographic perfusion
      imaging. Other indications for dobutamine stress echocardiography include risk
      stratification before noncardiac surgical procedures, risk stratification after
      myocardial infarction, and identification of viable myocardium in patients with
      left ventricular dysfunction. CONCLUSION: Dobutamine stress echocardiography is
      an accurate, safe, cost-effective, and portable procedure for the noninvasive
      diagnosis of coronary artery disease and for the preoperative assessment of
      patients with such disease, especially those who are unable to perform adequate
      exercise tests.

PMID- 7808048
TI  - Total potential frequency of autologous blood transfusion in Olmsted County, MN.
AB  - OBJECTIVE: To calculate the total "potential" frequency of preoperatively donated
      autologous erythrocyte (red blood cell or RBC) units in the entire population of
      patients who received transfusions in a specific US county, in a hypothetical
      situation in which all patients who received transfusions for elective surgical
      procedures (and were considered medically eligible for preoperative autologous
      blood donation [PABD]) predeposited a number of autologous RBCs appropriate for
      their procedure. MATERIAL AND METHODS: All Olmsted County residents who received
      RBC transfusions during 1991 and 1992 were retrospectively assessed for
      eligibility for PABD. Patients who were eligible to donate blood were assigned a
      number of autologous RBC predeposits appropriate for their scheduled procedure.
      Calculated total potential frequency figures for PABD were compared statistically
      on the basis of age, gender, and surgical service. RESULTS: Study patients were
      eligible for PABD in 459 of 1,038 surgical admissions. The percentage eligibility
      for PABD was similar across age and gender patient groups but differed across
      admitting surgical services. Reasons for ineligibility for PABD differed across
      the patient categories studied. Under the aforementioned assumption,
      theoretically 786 of the 8,137 RBC units transfused to all study patients (9.7%)
      could have been provided by PABD. CONCLUSION: From the standpoint of an entire
      community population, the total potential effect of PABD on the blood supply can
      amount to a maximum of 9.7% of all transfused units of RBCs, an upper limit that
      is similar across age and gender patient groups but differs across transfusing
      surgical services.

PMID- 7808047
TI  - Analysis of early failures after lumbar decompressive laminectomy for spinal
      stenosis.
AB  - OBJECTIVE: To determine why some patients have no improvement after surgical
      treatment of lumbar spinal stenosis. DESIGN: We conducted a retrospective study
      of patients who were referred to our institution between 1990 and 1993 because
      their symptoms were unchanged or worsened after lumbar decompressive laminectomy.
      MATERIAL AND METHODS: For the 45 study patients (25 women and 20 men; mean age,
      70.8 years), preoperative and postoperative clinical status, preoperative and
      postoperative imaging studies, and operative reports were analyzed. RESULTS:
      Preoperatively, only 23 patients (51%) had the clinical syndrome of neurogenic
      claudication, and 15 (33%) had midline low-back pain without a radicular
      component. Three other patients had peripheral neuropathy, and three had atypical
      leg pain. Only 10 patients had radiographic evidence of severe lumbar canal
      stenosis; the others had moderate, mild, or no stenosis. In 10 patients, surgical
      decompression was inadequate. Only three patients had the triad of neurogenic
      claudication, radiographically confirmed severe lumbar stenosis, and adequate
      decompression of the lumbar canal and lateral recesses. CONCLUSION: The most
      common pattern in patients with early failure after lumbar laminectomy was the
      absence of actual neurogenic claudication coupled with the absence of severe
      stenosis on preoperative imaging studies. The most common technical error was
      inadequate neural decompression. These data suggest that the outcome may be
      improved by more careful selection of patients and by performance of an adequate
      surgical decompression.

PMID- 7808049
TI  - 70th anniversary of the Mayo Clinic Proceedings.

PMID- 7808050
TI  - Venous and pulmonary thromboembolism: an algorithmic approach to diagnosis and
      management.
AB  - The frequently encountered disorder of venous thromboembolism (VTE) can cause
      serious morbidity and even death. Nevertheless, in more than 70% of patients who
      die of pulmonary embolism (PE), the diagnosis is not considered before death.
      Thus, clinicians should have a high index of suspicion for VTE, especially in
      high-risk patients. Some risk factors for VTE are a recent surgical procedure and
      general anesthesia, immobilization, congestive heart failure, previous PE,
      pregnancy, and oral contraceptive use. Before therapy can be initiated, a
      definitive diagnosis of VTE must be established. An algorithm for assessing
      patients with possible VTE is presented; decisions about proceeding with various
      studies are based primarily on the clinician's degree of suspicion for the
      presence of PE and the findings on a ventilation-perfusion scan. Elevation of the
      patient's legs before, during, and after a surgical procedure is a simple measure
      that may substantially decrease the occurrence of PE.

PMID- 7808052
TI  - Adults with congenital heart disease: patient knowledge of endocarditis
      prophylaxis.
AB  - OBJECTIVE: To determine whether adults with congenital heart disease have
      adequate knowledge of infective endocarditis and endocarditis prophylaxis and to
      ascertain whether an educational program effectively improves patient knowledge
      and compliance. MATERIAL AND METHODS: We asked 102 consecutive patients to
      complete a 12-question survey to assess their knowledge of heart disease,
      infective endocarditis, and endocarditis prophylaxis. RESULTS: Of 102 patients,
      100 (98%) completed the questionnaire. Sixty-eight patients knew the name of
      their heart disease. Fifty patients correctly defined endocarditis, but only 43
      knew hygiene measures that could prevent endocarditis. Ninety-six patients knew
      that they needed to take "a medicine" before dental procedures, and 76 of those
      patients (79%) knew that an antibiotic was necessary. Patient use of cardiac
      medications and a history of endocarditis correlated significantly with knowledge
      of endocarditis. Patients who had been to the Adult Congenital Heart Disease
      Clinic at least once knew endocarditis prevention measures and the importance of
      regular dental and cardiology follow-up significantly more frequently than did
      first-time attendees. Despite educational counseling, however, patient recall of
      endocarditis and its prevention is disappointing. CONCLUSION: Many adults with
      congenital heart disease have inadequate knowledge of their cardiac lesion,
      endocarditis, and endocarditis prophylaxis. Educational efforts for adults with
      congenital heart disease need to be updated and reinforced regularly.

PMID- 7808051
TI  - Stress echocardiography. Part I. Exercise echocardiography: techniques,
      implementation, clinical applications, and correlations.
AB  - OBJECTIVE: To describe the techniques and applications of exercise
      echocardiography. DESIGN: We review pertinent experimental and clinical studies
      from the literature and present our experience with the first 2,000 patients who
      underwent exercise echocardiography in our laboratory. MATERIAL AND METHODS: The
      indications for and contraindications to exercise echocardiography and the
      advantages, limitations, and accuracy of this procedure in comparison with other
      techniques for detecting coronary artery disease are discussed. RESULTS: Exercise
      echocardiography is increasingly used for the noninvasive evaluation of coronary
      artery disease because, in addition to its diagnostic capabilities, it offers
      attractive features such as portability, versatility, rapid availability of
      results, and relatively low cost. For accurate interpretation of the results, the
      workload achieved and the time between completion of exercise and image
      acquisition must be considered. The major limitation of exercise echocardiography
      is the high degree of operator dependence. For accurate interpretation of
      regional wall motion abnormalities and recognition of ischemic changes, specific
      training and extensive experience are necessary. CONCLUSION: Although exercise
      echocardiography has only relatively recently become a widely used technique, it
      has proved to have considerable accuracy in the diagnosis of coronary artery
      disease (mean sensitivity, 84%; mean specificity, 87%). In high-volume
      laboratories, feasibility studies have shown success rates between 90 and 99%;
      thus far, reproducibility has been satisfactory. Other applications of exercise
      echocardiography being studied are follow-up monitoring after revascularization,
      determination of prognosis, and assessment of valvular heart disease.

PMID- 7808053
TI  - Nonsteroidal anti-inflammatory drug-induced enteropathy: case discussion and
      review of the literature.
AB  - The adverse effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on the upper
      gastrointestinal tract are well described. Evidence also shows that NSAIDs can be
      harmful to the small intestine. The use of NSAIDs has been associated with small
      intestinal strictures, ulcerations, perforations, diarrhea, and villous atrophy.
      Herein we present a case of NSAID-induced enteropathy with multiple diaphragm
      like strictures that involved the distal 35 cm of ileum and review the literature
      of other cases of NSAID-induced enteropathy in which biopsy specimens were
      obtained for histologic analysis to rule out other causes. The prevalence of
      NSAID-induced enteropathy is unknown. Diagnosis can be made by endoscopy or at
      abdominal exploration. The role of radionuclide scans for diagnosis remains
      unclear. The pathogenesis is likely multifactorial. Mucosal diaphragms may be
      specific for NSAID-related disease. Treatment options for NSAID-induced
      enteropathy are discussed.

PMID- 7808054
TI  - An unusual case of the nonketotic hyperglycemic syndrome during childhood.
AB  - The nonketotic hyperglycemic syndrome is rare during childhood and may occur as
      the initial manifestation of insulin-dependent diabetes mellitus or during an
      episode of gastroenteritis. In this article, we report an unusual case of this
      syndrome in a female infant who had atypically severe hyperglycemia in
      association with gastroenteritis. In addition, we provide a review of the
      literature and summarize the pathophysiologic mechanisms of the nonketotic
      hyperglycemic syndrome.

PMID- 7808055
TI  - Cavitary pulmonary infarct in immunocompromised hosts.
AB  - Pulmonary disease in immunocompromised patients is common, but cavitary lung
      disease is less common and is usually associated with a fungal or mycobacterial
      infection. Pulmonary embolism is a noninfectious cause of a cavitary pulmonary
      process. Pulmonary embolism causes infarction in fewer than 15% of cases, and
      only about 5% of infarctions cavitate. Herein we describe two cases of cavitary
      infarcts in immunocompromised patients and review the clinical aspects of
      pulmonary infarcts and cavitation. Cavitary pulmonary infarction has been
      reported only rarely in immunocompromised patients. It is a dangerous but
      treatable pulmonary disease that must be considered in the differential diagnosis
      of immuno-compromised patients with lung disease.

PMID- 7808056
TI  - Insights into the pathogenesis and prevention of coronary artery disease.
AB  - OBJECTIVE: To present information about risk factor clustering and the oxidation
      hypothesis of atherosclerosis and attempt to synthesize these facts into a
      clinically relevant approach to patients with or at risk for coronary artery
      disease (CAD). MATERIAL AND METHODS: The total cholesterol level is a relatively
      weak marker for the risk of CAD. The levels of both high-density lipoprotein
      (HDL) cholesterol and remnants of triglyceride-rich lipoproteins and the inherent
      susceptibility of the low-density lipoprotein (LDL) particles to oxidative
      modification may be as important as the total or LDL cholesterol levels. LDL
      cholesterol must undergo oxidative modification by means of oxygen free radical
      processes before it becomes atherogenic. Patients with high levels of oxidative
      stress include those with risk factor clustering or insulin resistance (or both).
      Such patients are characterized by hypertension, truncal obesity,
      hypertriglyceridemia, depressed HDL cholesterol levels, and increased insulin
      levels. They also have increased levels of triglyceride-rich remnant lipoproteins
      and LDL particles that are characterized by their small dense nature and
      pronounced predisposition to oxidative modification. RESULTS: Biologic
      antioxidants seem to be promising therapy for the prevention of atherogenesis.
      Although long-term prospective data are not yet available, vitamin E has been
      shown to be effective in both animal and human models in preventing LDL
      oxidation, and it may have a role in the prevention of CAD. A healthy diet of
      fresh fruits, vegetables, and whole grains is beneficial because it improves the
      lipid levels and provides high levels of natural antioxidants. The atherogenic
      potential of hydrogenated polyunsaturated fats is approximately equivalent to
      that of saturated fats. Monounsaturated fat is inherently resistant to oxidation
      and may be protective against CAD. Niacin may be effective in patients with
      clustered risk factors. It has been found to convert the easily oxidized small
      dense LDL pattern to the large buoyant oxidation-resistant particles.
      Hydroxymethylglutaryl-coenzyme A reductase inhibitors are well tolerated and
      highly effective in decreasing LDL cholesterol, but they are expensive. Estrogen
      has multiple potentially beneficial effects relative to cardiovascular disease.
      CONCLUSION: Persons with or at high risk for CAD should be identified early and
      aggressively treated with a program that involves lifestyle changes, alterations
      in dietary intake, and pharmacologic therapy.

PMID- 7808057
TI  - 46-year-old man with chronic hemoptysis.

PMID- 7808058
TI  - Acute myocardial infarction: risk stratification in the thrombolytic era.

PMID- 7808059
TI  - Stress echocardiography: clinical influence and future role.

PMID- 7808060
TI  - Mayo Clinic Proceedings celebrates 70th year of publication.

PMID- 7808061
TI  - [Mini Mental State Examination: association of the score obtained with the age
      and degree of literacy in an aged population].
AB  - BACKGROUND: To differentiate dementia from the normal human decline scales may be
      used in an attempt to identity and quantify the cognitive damage which a subject
      may present. The Mini Mental State Examination (MMSE) is one of those. This study
      was performed to identify the relation of the responses between the MMSE and the
      sociodemographic variables of the subjects. METHODS: The MMSE was applied as a
      tool to determine the presence of cognitive alterations in a prospective study of
      people over the age of 65 years from La Selva del Camp (Baix Camp, Catalonia,
      Spain). The population was differentiated according to the cut off point (24
      points) with the relation of the score obtained by each subjects being studied
      with the sociodemographic variables of the same. RESULTS: The mean score obtained
      in the test by the total population was: (mean +/- SD) 23.9 +/- 4.5 points; 24.6
      +/- 4.9 in the males and 22.5 +/- 5.8 in the females. In the age group 65-74
      years the mean score was 24.8 +/- 3.8; 23 +/- 4.6 in those from 75-80 years and
      21.4 +/- 6 in the age group over 85 years. Sex was significantly associated (p =
      0.0003), as were age (p = 0.0002) and the degree of alphabetization (p = 0.0000)
      with women obtaining a lower MMSE score than men, the most elderly was lower than
      that obtained by the younger and those of less alphabetization lower than those
      with education. CONCLUSIONS: Although the MMSE is a good tool for the detection
      of cognitive alterations in a population, it must be kept in mind that the result
      of this test may be influenced by the age and education of the subject and should
      therefore not be used as an exclusive element in the diagnosis of dementia.

PMID- 7808062
TI  - [Strategies in screening of nonclassical forms of congenital adrenal hyperplasia
      caused by P450c21 deficiency in hyperandrogenic women].
AB  - BACKGROUND: The value of the measurement of the serum level of 17
      hydroxyprogresterone (170HP) and the stimulation test with adrenocorticotropin
      (ACTH) with and without previous slowing with dexamethasone was determined to
      detect congenital adrenal hyperplasia (CSH) due to a deficiency of P450c21 in
      hyperandrogenic women. METHODS: Three hundred seventy women consecutively
      attended for hyperandrogenism were studied. Stimulation tests of 170HP were
      performed with 250 micrograms i.v. of synthetic ACTH with previous administration
      of 1 mg of dexamethasone in 191 of the patients. The test was performed without
      previous dexamethasone in the remaining 179 patients. RESULTS: Nineteen patients
      with unclassical forms of CSH by deficiency of P450c21 were detected. Another 19
      were considered as probable heterozygotes. The basal levels of 170HP with and
      without previous dexamethasone showed negative predictive value of nearly 100%,
      indicating the validity of their use in selecting patients for the stimulation
      test. No significant differences were seen in the increases of post ACTH 170HP
      observed between the tests carried out with and without dexamethasone.
      CONCLUSIONS: The frequency of congenital adrenal hyperplasia by deficiency of
      P450c21 in the hyperandrogenic women studied was found to be 5.1%. The low
      frequency together with the predictive value of the basal concentrations of 170HP
      indicate that the systematic routine use of the ACTH test as a means of scrutiny
      of CSH in hyperandrogenic women is unjustified.

PMID- 7808063
TI  - [Comparison of 2 methods of evaluation of food and nutrient intake: 24-hour
      recall and semiquantitative frequency questionnaire].
AB  - BACKGROUND: Methods of dietary collection at an individual level include various
      procedures with different estimates of food, energy and nutrients intakes. The
      aim of this study was to compare two dietary methods widely used in nutritional
      epidemiology: a 24-hour recall and a semiquantitative food frequency
      questionnaire. METHODS: One hundred and fifty-five people selected at random from
      the population of the Valle de Aran (Lerida, Spain) were surveyed. Nutritional
      intake information was obtained from both methods. RESULTS: The frequency method
      overestimated all the nutrient intakes only before adjustment by energy intake,
      except for cholesterol. After adjustment by energy intake estimations from both
      questionnaires were very similar; the percentages of energy supplied by proteins,
      fatty acids and carbohydrates were very similar, too; the
      polyunsaturated/monounsaturated fatty acid ratios, were almost the same. Results
      show a level of correlation between the questionnaires that ranges from 0.81 to
      0.23. Nutrients that showed the highest crude correlation between both
      questionnaires were alcohol, energy, carbohydrates, sodium and iodine (R > or =
      0.7) while vitamins C, B1, B6, B12, and A, niacine, folic acid, iron, phosphorus
      and potassium showed the lowest (R < or = 0.5). Energy adjusted correlations were
      quite different to unadjusted ones particularly for lipids, monounsaturated fatty
      acids, carbohydrates, fiber, cholesterol, zinc and sodium, for which a lower
      coefficient was calculated after adjustment, and vitamins B2, B6, C, D and
      potassium, for which a higher coefficient was estimated after energy adjustment.
      CONCLUSIONS: Both methods make similar assessments when adjusting for caloric
      intake, but food frequency questionnaire tends to overestimate food consumption.

PMID- 7808064
TI  - [From sanity to dementia: a journey without return].

PMID- 7808065
TI  - [Burdened women].

PMID- 7808066
TI  - [Medical-clinical audit. I. Quality of health care services].

PMID- 7808067
TI  - [Q fever].

PMID- 7808068
TI  - [Blood ammonium as a possible early marker of graft viability in liver
      transplantation].

PMID- 7808069
TI  - [Chronic massive and idiopathic pericardial effusion with spontaneous
      resolution].

PMID- 7808070
TI  - [Chronic eosinophilic pneumonia in a patient treated with allogeneic bone marrow
      transplantation].

PMID- 7808071
TI  - [Paralysis associated with weight loss and hyperthyroidism].

PMID- 7808072
TI  - [Fungemia caused by Candida krusei in a female patient with AIDS].

PMID- 7808073
TI  - [Cystic fibrosis in Asturias: an elevated frequency of the delta F508 mutation].
AB  - BACKGROUND: Cystic fibrosis (CF) is the most common autosomic-recessive inherited
      disorder. More than 300 different mutations in the CF gene (CFTR) have been
      described, being delta F508 and G542X the most common in the Spanish population.
      The frequencies of these mutations vary between the different European
      populations. METHODS: We have studied the delta F508 and G542X mutations in 20 CF
      patients from Asturias. These mutations were analysed through the polymerase
      chain reaction (PCR). RESULTS: The frequency of the delta F508 mutation in
      Asturias was 77.5%, higher than those found in most of the other Spanish
      populations. The frequency found in Asturias is close to the frequency described
      for the Basque Country population. Patients homozygous for the delta F508
      mutation showed clinical symptoms similar to those described in studies on other
      populations. CONCLUSIONS: The high frequency of two mutations in the CFTR gene in
      Asturias makes possible the direct diagnostic in most families. The delta F508
      mutation is associated to severe clinical manifestations, like early pancreatic
      insufficiency and Pseudomonas infection.

PMID- 7808074
TI  - [Janz's juvenile myoclonic epilepsy: a little-known frequent syndrome. A study of
      85 patients].
AB  - BACKGROUND: Juvenile myoclonic epilepsy (JME) constitutes 10% of all epilepsies.
      Despite this syndrome being well defined, its diagnosis is usually delayed. The
      aim of this study was to analyze the clinical and electroencephalographic
      characteristics to facilitate guidelines to contribute to its recognition.
      METHODS: From January 1986 to July 1993 the clinical and EEG data of 85 patients
      with JME were prospectively studied. In 68 cases (80%) the polygraphic study of
      sleep was also analyzed during a nap period. RESULTS: The series included 44
      males and 41 females of a mean age of 28 years (range: 13-63). Fifty-six percent
      of the cases showed family history of epilepsy and/or febrile convulsions. All
      the patients had myoclonic crisis with the age of 15 being the mean age of
      initiation (range: 8-27). Eighty-seven percent also had generalized tonic-clonic
      crisis and 18% typical absences. Myoclonias were presented daily up the
      administration of adequate treatment in 60% of the cases with 21% having
      myoclonic status. The mean interval from the initiation of the myoclonic crisis
      to diagnosis of JME was of 10.6 years. On monotherapy with valproic acid and
      following a mean follow up period of 23.8 months, 86% of the patients remained
      free of crisis. Nonetheless, the rate of recurrence was 100% in the 19 patients
      who discontinued the treatment. Surveillance EEG was normal on some occasion in
      88% of the cases. The most characteristic paroxysms were the following: wave
      point at 4-5 Hz and generalized rapid wave-polypoint. Light stimulation provoked
      a paroxysmal response in one third of the cases. Sleep EEG was abnormal in all
      the patients. An activation of the paroxysms during non-REM sleep in 78% of the
      cases and on waking up in 25%. CONCLUSIONS: Juvenile myoclonic epilepsy is a well
      defined syndrome. Its diagnosis is based on directed anamnesis allowing myoclonic
      jerks to be collected which often remain unperceived, and EEG exploration with
      sleep tracing in which the characteristic outbreaks of wave-point or generalized
      rapid wave-polypoints may be discovered.

PMID- 7808075
TI  - [The effect of the type of factor VIII concentrate on the CD4 lymphocyte count in
      hemophiliacs with human immunodeficiency virus infection: the results of a meta
      analysis].
AB  - BACKGROUND: The administration of factor VIII concentrates of intermediate purity
      in HIV+ hemophiliac patients has been related with disorders of the immunologic
      system of these patients which may be observed in a more acute decrease in CD4
      lymphocyte count in relation to that described in patients treated with products
      of greater purity. The present study evaluates the impact of these treatments
      (concentrates of intermediate or high purity) on the immune system of HIV+
      hemophiliac patients by exhaustive analysis of the literature. METHODS: Meta
      analysis of 8 clinical studies published between 1983 and 1993 was performed by
      multivariate analysis which considers the decrease in the number of CD4
      lymphocytes as an indicator of the evolution of the disease. Likewise, the size
      of the effect and combined significance were also evaluated. RESULTS: The
      absolute decrease in the number of CD4 lymphocytes is significantly lower in
      patients treated with products of greater purity (354 +/- 52 vs 448 +/- 54
      cells/microliters p = 0.037) as was the size of the effect and the different
      tests of combined significance. The speed of decrease was between 1.25 and 16.55
      cells/microliters/year lower in the treated group than in the control (p =
      0.029). CONCLUSIONS: According to meta-analysis, the factor VIII concentrates of
      intermediate purity influence the immune system of HIV+ hemophiliac patients to a
      greater extent leading to a more acute decrease in the number of CD4 lymphocytes
      over time. Further studies are required to confirm whether this facts leads to
      differences in clinical manifestations of the infection or in survival.

PMID- 7808076
TI  - [Thyroid hormone and bone mass].

PMID- 7808077
TI  - [Is the presumption of consent necessary in organ donation for transplantation?].

PMID- 7808078
TI  - [The basic treatment of arterial hypertension (II). Pharmacological treatment].

PMID- 7808079
TI  - [The biomedical actions of lithium: current controversies and therapeutic
      possibilities].

PMID- 7808080
TI  - [The early detection by magnetic resonance of bone infiltration in HIV-related
      lymphomas].

PMID- 7808081
TI  - [Dying in April. Comments on opinions on health centers].

PMID- 7808082
TI  - [Shut in with only one toy].

PMID- 7808083
TI  - [The prevalence of dyspepsia in Spain].

PMID- 7808084
TI  - [alpha-Glutathione transferase as an early index of acute graft rejection in
      liver transplantation].

PMID- 7808085
TI  - [The participation of physicians in mail surveys].

PMID- 7808086
TI  - Hypoglycemia.
AB  - Hypoglycemia is the most common endocrine medical emergency. Because the brain
      has an obligatory need for contiunous inflow of glucose, any interruption to that
      supply puts the individual at risk for neuroglycopenia. The latter impairs brain
      function and precludes self-administered corrective treatment. Treatment of
      hypoglycemia, especially in those patients with diabetes mellitus, involves
      punctilious attention to preventive measures. The acute event, if recognized,
      requires treatment with oral ingestion of free carbohydrate. Neuroglycopenia can
      be treated equally effectively with intravenous glucose or parenteral glucagon
      administration.

PMID- 7808087
TI  - Bilateral massive adrenal hemorrhage.
AB  - A systematic review of the etiopathogenesis of adrenal hemorrhage reveals that
      the factors that determine the occurrence of this complication in a patient can
      be identified prospectively. Such prospective diagnostic suspicion allows the
      significance of the otherwise nonspecific clinical features heralding this
      catastrophe to be appreciated in the precrisis interval. Confirmation of the
      diagnosis is achieved by visual demonstration of bilaterally enlarged and
      hyperdense adrenal glands on a CT scan and by demonstration of adrenocortical
      failure on hormonal evaluation. Preemptive steroid therapy and diagnostic
      evaluation during the precrisis period prevent the occurrence of a potentially
      disastrous adrenal crisis in a patient who is seriously ill from other problems
      and who cannot afford a setback of this severity. Because steroid therapy delayed
      until the stage of crisis may be unsuccessful in salvaging such a patient,
      prospective recognition must be based on identifying the patient at risk for BMAH
      and recognizing the significance of the nonspecific clinical features that
      accompany it in the appropriate clinical context.

PMID- 7808089
TI  - Hyponatremic emergencies.
AB  - Hyponatremia is a common clinical problem and can result in severe morbidity and
      even death. Understanding the pathophysiology of hyponatremic encephalopathy is
      central to accurate diagnosis and management. This article reviews the
      controversies surrounding the treatment of hyponatremia with special emphasis on
      risk to benefit ratio of different therapeutic strategies.

PMID- 7808088
TI  - Pheochromocytoma. Update on diagnosis, localization, and management.
AB  - Pheochromocytoma, although rare, is associated with a high degree of morbidity
      and mortality if not recognized. A high degree of suspicion in patients with new
      onset hypertension; hypertension with sudden worsening or development of diabetes
      mellitus; or a family history of MEN, neuroectodermal tumors, or simple
      pheochromocytoma should prompt biochemical confirmation with either 24-hour urine
      catecholamines (norepinephrine and epinephrine) or total MET (NMET plus MET).
      Following confirmation of the diagnosis, radiologic studies with CT and (if
      needed) MIBG are employed to localize the tumor. Surgical removal is the only
      definitive therapy. Medical management with alpha-blocking agents, to control
      symptoms and prevent a hypertensive crisis, is generally advocated for 2 weeks
      preoperatively and intraoperatively. Occasionally, beta-blockers, employed only
      after adequate alpha-blockade, are necessary to control tachycardia and
      tachyarrhythmias. High-dose MIBG and combination chemotherapy have been used
      adjunctively to treat malignant pheochromocytoma, although neither modality
      provides lasting satisfactory results. Normal urine assays performed 2 weeks
      postoperatively ensure the complete removal of all tumor. Additionally, lifelong
      follow-up (yearly initially) is necessary to detect any signs of benign
      recurrence or malignancy because these have been reported to occur as long as 41
      years after the initial surgical resection. Biochemical evidence of excess
      catecholamine production usually precedes the clinical manifestations of
      catecholamine excess when these tumors recur.

PMID- 7808090
TI  - Thyroid storm.
AB  - Despite earlier recognition and treatment of hyperthyroidism, thyroid storm
      remains a life-threatening, although fortunately rare, medical emergency. Prompt
      recognition and aggressive treatment employing a multifaceted approach are
      generally effective at correcting the homeostatic decompensation that is the
      hallmark of thyroid storm. Research is furthering understanding of the cellular
      actions of thyroid hormone and may lead to additional, even more effective
      treatment modalities in the future.

PMID- 7808091
TI  - Myxedema coma. Pathophysiology, therapy, and factors affecting prognosis.
AB  - Myxedema coma is a fatal condition when left unrecognized. With the advent of
      intensive supportive therapy and the use of intravenous thyroxine, however,
      mortality for this disorder is declining. Further insights into the
      pathophysiology of hypothyroidism should lead to more rational approaches to
      therapy and result in improved survival.

PMID- 7808092
TI  - Graves' ophthalmopathy.
AB  - Graves' ophthalmopathy is an organ-specific autoimmune process strongly linked to
      Graves' hyperthyroidism. Although the hyperthyroidism can be successfully
      treated, it is often the ophthalmopathy that produces the greatest long-term
      disability for patients suffering from this disease. Eyelid retraction,
      proptosis, periorbital edema, chemosis, and disturbances of ocular motility have
      both cosmetic and functional consequences. In some cases, the disease may
      progress to visual loss by exposure keratopathy or compressive optic neuropathy.
      This article discusses the manifestations of Graves' ophthalmopathy that require
      urgent attention and the relationship of the activity of Graves' ophthalmopathy
      to thyroid function status.

PMID- 7808093
TI  - The endocrine response to critical illness.
AB  - The endocrine response to stress is complex. Elevations in the serum
      concentrations of the "classic" stress hormones, epinephrine and cortisol, occur
      following many kinds of physiologic challenge and are accompanied by elevations
      in corticotropin, GH, and glucagon levels. These changes are probably responsible
      for the hyperglycemia and hypercatabolism common to most critical illness. If
      volume depletion is present, vasopressin, renin, and aldosterone secretion are
      also likely to be stimulated. These hormones, if present in excess, may produce
      fluid retention and hyponatremia. In some critically ill patients, there is a
      dissociation of renin and aldosterone production called hyperreninemic
      hypoaldosteronism, but the clinical importance of this syndrome is poorly
      understood. Thyroid hormone metabolism is commonly affected by critical illness,
      which results in characteristic abnormalities of thyroid function testing known
      as the euthyroid sick syndrome. The reproductive axis is exquisitely sensitive to
      physiologic stress; hypogonadotropic hypogonadism is a common finding in critical
      illness. The ongoing challenge to the clinician is to determine whether seemingly
      abnormal hormone measurements in critically ill patients reflect an appropriate
      homeostatic response to severe illness or, instead, whether they denote an
      independent metabolic disorder that might actually cause or contribute to the
      patient's unstable condition. In view of the exceedingly complex (and poorly
      understood) interactions involved in the human response to a severe illness, a
      thoughtful approach to the whole patient is essential and far preferable to
      indiscriminate hormone testing. Such testing, at best, may be uninterpretable in
      light of the clinical circumstances or, at worst, may lead to therapeutic
      misadventures.

PMID- 7808094
TI  - Nonketotic hypertonicity in diabetes mellitus.
AB  - Nonketotic hypertonicity (NKH) is one of the most common endocrine emergencies.
      It is more common in the elderly patient with noninsulin-dependent diabetes
      mellitus but may occur in insulin-dependent diabetes as well. Although there are
      many possible precipitating causes, the final common pathway is usually decreased
      access to water. Treatment consists of vigorous hydration, electrolyte
      replacement, and small amounts of insulin. Most deaths from NKH occur in the
      first 2 days of hospitalization; therefore, a significant decrease in morbidity
      and mortality can be expected by education of patients and their caregivers in
      the prevention of NKH.

PMID- 7808095
TI  - Infectious emergencies in patients with diabetes mellitus.
AB  - Although it remains controversial as to whether diabetics have an overall
      increased incidence of infection as compared to nondiabetics, several potentially
      life-threatening infections do appear to be uniquely associated with diabetes.
      These infections generally occur in older diabetics with less than optimal
      glucose control. For each entity, selected symptoms and signs may suggest the
      diagnosis but confirmation of via tissue biopsy with culture and histopathology
      or radiography is usually necessary. Management typically require both
      antimicrobial treatment and surgery.

PMID- 7808096
TI  - Hypercalcemic crisis.
AB  - Hypercalcemic crisis or severe hypercalcemia represents a life-threatening
      emergency. The most common cause is hypercalcemia of malignancy, although
      granulomatous diseases, previously undetected primary hyperparathyroidism,
      medication-induced hypercalcemia, and a few rarer causes may result in this
      endocrine emergency as well. The clinical presentation and prognosis depend on
      the acuity of the development of hypercalcemia, the degree of hypercalcemia, and
      the underlying cause. Certainly, patients with malignancy who develop
      hypercalcemia superimposed on their already debilitated state are more likely to
      have a poor outcome than a previously relatively healthy patient with thiazide
      induced hypercalcemia, for example. The clinical presentation of patients with
      hypercalcemic crisis varies depending once again on the underlying cause and
      degree and rapidity of the hypercalcemia. Most patients experience some
      constitutional symptoms, neurologic symptoms, gastrointestinal symptoms, and
      renal manifestations of hypercalcemia. Immediate and effective therapy directed
      toward the pathophysiology of hypercalcemia is essential. General measures must
      be implemented to reverse the dehydration, to promote urinary calcium excretion,
      to avoid prolonged immobilization, and to identify the underlying cause of
      hypercalcemia. Specific measures directed at inhibiting bone resorption,
      increasing renal sodium and calcium excretion, and occasionally at decreasing
      intestinal absorption of calcium (or more specifically blocking vitamin D
      metabolism) should also be implemented. Obviously the more reversible the
      underlying cause of hypercalcemia, the more aggressive one should be with the
      therapy. The literature was reviewed to compile comparative data that
      practitioners may use in choosing among the various pharmacologic therapies
      available for the treatment of acute hypercalcemia. Despite all the advances in
      the field, hypercalcemic crisis still carries a significant mortality risk,
      although with appropriate therapy with the aforementioned general and specific
      measures, the calcium level can effectively be lowered in most patients.

PMID- 7808097
TI  - Diabetic ketoacidosis.
AB  - This article reviews the pathogenesis of diabetic ketoacidosis (DKA) and provides
      a rational approach to the management of patients with DKA. The therapeutic
      discussion includes the use of low-dose insulin, no bicarbonate, or phosphate
      therapy on the majority of DKA patients, based on numerous prospective randomized
      studies. The article also discusses controversial subjects such as the use of
      hypotonic versus isotonic saline with and without colloids, hydration of subjects
      before insulin therapy, and admission of DKA patients to the general ward versus
      emergency ward versus intensive care unit. A concise, simple protocol is also
      presented as a suitable reference for management of patients with DKA.

PMID- 7808098
TI  - Hypocalcemic emergencies.
AB  - Chronic hypocalcemia occurs frequently, although emergent hypocalcemia does not.
      When hypocalcemia is suspected, verification of ionized hypocalcemia is required
      and an etiopathologic search warranted. Etiology-specific therapy is suggested,
      although at times emergent intravenous calcium is indicated. Long-term
      nonspecific therapy includes oral calcium and vitamin D supplementation.

PMID- 7808099
TI  - Magic bullet: the history of oral rehydration therapy.

PMID- 7808100
TI  - "Bred up in the study of that faculty": licensed physicians in north-west
      England, 1660-1760.

PMID- 7808101
TI  - Changing disease identities: cretinism, politics and surgery (1844-1892).

PMID- 7808102
TI  - The homoeomerous parts and their replacement by Bichat's tissues.

PMID- 7808105
TI  - [Cortisone therapy of brain cancer].

PMID- 7808104
TI  - [What happened to the US health care reform?].

PMID- 7808103
TI  - Illustrations from the Wellcome Institute Library. The Royal Army Medical Corps
      'Muniment Collection'.

PMID- 7808106
TI  - [Prognosis of HIV infection and AIDS. What happened since the 1980's?].

PMID- 7808107
TI  - [Reduced number of abortions. Result of easily accessible and qualitative
      contraception counseling and cheap oral contraceptives].

PMID- 7808108
TI  - [Listening to the ideas of adolescents... An important source of knowledge for
      contraception counsellors].

PMID- 7808109
TI  - [The man behind the Bankart injury. He introduced a new technique for shoulder
      joint dislocation].

PMID- 7808110
TI  - [A quality study at a department of emergency surgery. The level of competence
      doesn't effect the quality].

PMID- 7808111
TI  - [Sick from amalgam? A connection with common disorders is not proven but patients
      should be carefully examined].

PMID- 7808112
TI  - [Pravidel may cause pulmonary changes. Signs of inflammatory activity and weight
      loss are part of the picture].

PMID- 7808113
TI  - [Research, development, health care services in the EEC. 115 billions for new
      progress].

PMID- 7808114
TI  - [The milk-alkali syndrome behind hypercalcemia. Careful drug anamnesis is
      important].

PMID- 7808115
TI  - [A box that become a tool. A flexible aid for quality development].

PMID- 7808116
TI  - [Apply the children's convention also to refugees].

PMID- 7808117
TI  - [Etiology of Budd-Chiari syndrome].

PMID- 7808118
TI  - [Neonatal care. What is the minimum acceptable bed capacity?].

PMID- 7808119
TI  - [Double scrutiny of mammographic screening is effective!].

PMID- 7808120
TI  - [Anti-Helicobacter therapy for each and everyone?].

PMID- 7808121
TI  - [Positive discoveries on hyaluronan should be tested in a new trial].

PMID- 7808122
TI  - [Highly sensitive markers of myocardial damage. Diagnostic progress or reason for
      confusion?].

PMID- 7808123
TI  - [Peritoneal dialysis as a cause of weight gain. The patients gain weight in spite
      of reduced appetite].

PMID- 7808125
TI  - [Adults with Down syndrome as a new therapeutic group. Importance of looking for
      organ changes].

PMID- 7808124
TI  - [Incidence of myelodysplastic syndrome is increasing. Careful diagnosis is
      necessary for choice of the treatment].

PMID- 7808126
TI  - [Laparoscopy is not suitable in malignant tumors. Risk of neoplasm seeding by
      instrument].

PMID- 7808127
TI  - [Life-threatening hemorrhage caused by anticoagulants. Inguinal pain was the
      first symptom].

PMID- 7808128
TI  - [Partial paralysis after difficult labor. A complication with good prognosis].

PMID- 7808129
TI  - [Depression is common in Parkinson disease. Limited studies on symptoms and
      treatment].

PMID- 7808130
TI  - [Coronary atheromatosis with effort angina in a young patient. Balloon dilatation
      is better than bypass surgery].

PMID- 7808131
TI  - [Reduced cholesterol in women. Wrong therapy after drug information].

PMID- 7808132
TI  - [The "plague bomb" in India seen in a historical perspective].

PMID- 7808133
TI  - [On the tracks of epidemics. Misplaced reliance on authority and new medical
      ideas].

PMID- 7808134
TI  - [Clauses of conscience in education. A conflict between students and patients].

PMID- 7808136
TI  - [Bandage for relief in Herpes zoster].

PMID- 7808135
TI  - [The quality of ICU is threatened by its division. Keep the care of children and
      adults together].

PMID- 7808137
TI  - [Exercise is effective in back pain].

PMID- 7808138
TI  - [Protection against diphtheria in Sweden is deficient among the elderly. Better
      documentation of vaccination is desirable].

PMID- 7808140
TI  - [Increasing number of diphtheria cases in Russia and Latvia].

PMID- 7808139
TI  - [Poliomyelitis, tetanus and diphtheria. May anamnesis show the need for increased
      number of vaccinations?].

PMID- 7808141
TI  - [Need for supplementary vaccination against diphtheria. Protection is
      insufficient, especially among women over 40 years of age].

PMID- 7808142
TI  - ["Restrict the indications for macrolide therapy." Overuse is an ecological
      risk].

PMID- 7808143
TI  - [Collective fines for over-prescription? A German model for reduced use of
      antibiotics].

PMID- 7808144
TI  - [Paroxysmal fibrillation as a clinical problem. More studies on the anxiety
      inducing disorder are needed].

PMID- 7808145
TI  - [Allergy to balloons. A case of severe latex allergy outside of risk groups].

PMID- 7808146
TI  - ["You are in bed with the Vatican!" On family planning during 20 years of work in
      developing countries].

PMID- 7808147
TI  - [August Bondeson--physician and story-teller. He created the immortal teacher
      Chronschough].

PMID- 7808148
TI  - [A substantial part of health resources is reserved for the dying. Cost analysis
      of terminal care].

PMID- 7808149
TI  - [Binswanger disease. A blood pressure-related dementia].
AB  - Interest in Binswanger's disease has increased during the past decade, owing to
      the possibility of detecting white matter changes with computerised and magnetic
      resonance tomography. This paper consists in a summary of clinical symptoms and
      signs and possible diagnostic criteria, discussion of differential diagnosis, and
      the presentation of two own cases. Both patients manifested mild dementia and
      gait disturbance, and one had frequent drop attacks. Severe supra- and infra
      tentorial white matter changes were present in both cases. It is important to
      consider a possible diagnosis of Binswanger's disease, as treatment of the
      appropriate risk factors may prevent or delay the development of dementia.

PMID- 7808150
TI  - [The man behind the syndrome. He prohibited isolation, strait-jackets and
      physical punishment].

PMID- 7808151
TI  - [Evaluation of medical technology. International cooperation saves resources and
      improves quality].

PMID- 7808152
TI  - [Deep venous thrombosis and pulmonary embolism--guidelines for prevention and
      treatment].

PMID- 7808153
TI  - [Negative effects of steroids on bone mass. Guidelines for prevention of
      osteoporosis].

PMID- 7808154
TI  - [Collapse of the health care in Cuba. Is it a results of the US embargo or is it
      self-inflicted?].

PMID- 7808155
TI  - [Older and older. Is Sweden prepared to meet care demands of the oldest old?].

PMID- 7808156
TI  - [Defend the honour of junior physicians!].

PMID- 7808157
TI  - [Myocardial infarction among women. Is it possible to prevent?].

PMID- 7808158
TI  - [A valuable test in infectious diseases. C-reactive protein gives better
      guidelines than blood sedimentation].

PMID- 7808159
TI  - [Mycotic infections in neutropenic patients. Necessary with adequate prevention].

PMID- 7808160
TI  - [Foot surgery. Diseases of the forefoot, a group treated by many specialists].

PMID- 7808162
TI  - [Cyclic pain. A late complication after endometrial resection and sterilization].

PMID- 7808161
TI  - [A pilot study on recurrent thrombosis of the coronary vessels. Selective
      infusion of urokinase is an effective treatment].

PMID- 7808163
TI  - [Childhood asthma and family interactions. Contradictory results on
      psychogenesis].

PMID- 7808164
TI  - [Broad spectrum antibiotics in pneumonia. The use is alarmingly increasing].

PMID- 7808165
TI  - [What happens behind closed doors when physicians become a problem? Informal
      mechanisms are revealed in a case study].

PMID- 7808167
TI  - [Survey of results of psychotherapy. Definitely significant positive effects].

PMID- 7808166
TI  - [External clinical audit of inguinal hernia surgery. Survey of four departments
      of surgery in Stockholm].

PMID- 7808168
TI  - [Biological causes of aggression. Combine environment and biological approach!].

PMID- 7808169
TI  - [Children with multiresistant pneumococci. "Keep the carriers out of day care
      centers"].

PMID- 7808170
TI  - [The small birthing unit: security risk or safety factor?].

PMID- 7808171
TI  - [Nalidixic acid--a forgotten alternative].

PMID- 7808172
TI  - [A not especially informative article about chronic fatigue].

PMID- 7808173
TI  - [Disgusting recruiting of patients].

PMID- 7808174
TI  - [Unique increase of celiac disease in Sweden. A possible clue to the pathogenesis
      of the disease].

PMID- 7808175
TI  - [Is tube insertion tympanostomy in children used unnecessarily? Swedish
      recommendations are well-founded].

PMID- 7808176
TI  - [Radon in dwellings and lung cancer. Smoking is more than an additional risk
      increasing factor].

PMID- 7808177
TI  - [Will "snoring children" become adults with sleep apnea?].

PMID- 7808178
TI  - [Rhinitis medicamentosa, an increasing problem. Do nose drops adversely affect
      bacterial infections?].

PMID- 7808179
TI  - ["Every other grave is a child's grave". Dramatic deterioration of health care
      services is a hard blow against the weak in Kosovo].

PMID- 7808181
TI  - [The mentally handicapped are neglected. They are deprived of their right to
      daily activities].

PMID- 7808180
TI  - [Infant food and celiac disease. Risk of increase when changing the diet].

PMID- 7808182
TI  - [Colleagues act often too late against Swedish physicians with problems. Great
      tolerance against "private" alcohol problems].

PMID- 7808183
TI  - [Ethical analysis in a workday of the general practitioner. A source of knowledge
      and development of competence].

PMID- 7808184
TI  - Lines of defense: domestic violence awareness month.

PMID- 7808185
TI  - Understanding survival responses of battered women.
AB  - Battered women often endure years of physical, psychological, and/or sexual abuse
      at the hands of an intimate partner. To intervene effectively, health
      professionals need to understand both the external factors and the complex
      conditioning process that keep many women trapped in abusive relationships. Many
      of the physical and psychological symptoms shown by battered women can be
      understood as complex survival strategies and responses to the abuse.

PMID- 7808186
TI  - Treating perpetrators of adult domestic violence.
AB  - This article reviews the emerging research on domestic violence offenders. A
      number of psychological and behavioral factors are correlated with battery,
      including pervasive psychological abuse, alcohol problems, violence in the family
      of origin, emotional insecurity, and features of antisocial and borderline
      personality disorders. Youthfulness, low socioeconomic status, and low
      educational attainment are also correlated with marital violence, yet it is
      common in all demographic groups. Research on the effectiveness of counseling for
      domestic violence perpetrators is quite limited. Some studies have shown that
      counseling adds significantly to the effects of arrest in reducing domestic
      violence. High recidivism rates are common, however, with over 25% of offenders
      engaging in physical aggression within one to two years after treatment.
      Counseling for domestic violence perpetrators should be part of a coordinated
      community response that includes criminal justice interventions, preventive
      education, and comprehensive victim services.

PMID- 7808187
TI  - Domestic homicide: risk assessment and professional duty to warn.
AB  - Battering has been associated with increased risk of homicide in the home.
      Homicide involving partners in a current or past intimate relationship may not
      have the same characteristics as other homicides. Physicians, nurses, and other
      health care professionals--who frequently see battered women as patients--should
      understand the dynamics, risk factors, and legal responsibilities related to
      domestic homicide in order to help prevent this form of violence.

PMID- 7808188
TI  - Joint Commission on Accreditation of Healthcare Organizations standards to
      improve care for victims of abuse.

PMID- 7808189
TI  - Legal protection for domestic violence victims: a guide for the treating
      physician.

PMID- 7808190
TI  - The Domestic Violence Medical Response Act.

PMID- 7808191
TI  - Legislative advances gained by passage of the Domestic Violence Act of 1994.

PMID- 7808192
TI  - Physicians and domestic violence programs: partners in change.

PMID- 7808193
TI  - Developing the Maryland Physicians' Campaign Against Family Violence. An
      interview with Med Chi's chief operating officer, Roseanne Matricciani. Interview
      by Ruth M. Seaby.

PMID- 7808194
TI  - Advocacy can make a difference.

PMID- 7808195
TI  - Summary of the NIH consensus. Helicobacter pylori in peptic ulcer disease.

PMID- 7808196
TI  - Med Chi and health system reform.

PMID- 7808197
TI  - Cancer mortality in Maryland: when being a leader is not best.
AB  - Maryland has the second highest statewide cancer mortality rate in the nation.
      This ranking is primarily due to high death rates for the most prevalent cancers:
      lung, breast, colon, and prostate. Based on the recent literature and the October
      1991 preventive medicine grand rounds at the Johns Hopkins University School of
      Hygiene and Public Health, this paper summarizes several current viewpoints on
      cancer mortality in Maryland and the progress that has been made by recently
      instituted state and community initiatives.

PMID- 7808198
TI  - Correlation of DNA flow cytometry and hormone receptors with axillary lymph node
      status in patients with carcinoma of the breast.
AB  - Axillary lymph node dissection (ALND) remains a standard staging procedure for
      patients with primary carcinoma of the breast. In a retrospective review of 63
      patients with primary breast cancer who underwent ALND, statistical analysis
      showed that only tumor size was correlated with axillary lymph node involvement.
      Neither hormone receptor status, ploidy, nor percent S-phase contributed more to
      prediction of nodal size. Statistical analysis also indicated a significant
      correlation between receptor-negative status and the presence of positive
      axillary lymph nodes.

PMID- 7808199
TI  - Bilateral involvement of the cerebellopontine angles by malignant melanoma
      metastasis: a case report.
AB  - Most tumors located at the cerebellopontine angle (CPA) are benign lesions,
      usually of neuroectodermal origin. This report describes a case of malignant
      melanoma with bilateral involvement of the CPA.

PMID- 7808201
TI  - Neutropenia and fever in patients receiving chemotherapy in a community teaching
      hospital: results of a retrospective chart review.
AB  - A retrospective chart review study of factors that may influence the outcome of
      cancer patients hospitalized with febrile neutropenia indicates that positive
      microbial cultures, older age, and hematologic malignancies may be associated
      with poor outcome (death during the hospitalization). The absolute neutrophil
      count was statistically significant only in patients with positive cultures. Good
      outcome was associated with negative microbial cultures and shorter length of
      hospital stay.

PMID- 7808200
TI  - Radiotherapy for cancer of the larynx: review of a community hospital experience.
AB  - Records of 106 patients with squamous cell carcinoma of the larynx treated with
      radiation therapy (RT) at Washington Adventist Hospital between 1976 and 1988
      were analyzed for patterns of failure and survival, with a minimum of five-year
      follow-up. In patients treated with RT alone, initial local control rate was 72%
      for tumors involving supraglottic larynx and 90% for glottic larynx; in
      postoperative RT patients, the rate was 65% in the supraglottic and 67% in the
      glottic larynx group. The laryngeal preservation rate in patients treated with RT
      alone was 87% in those with early lesions (T1 and T2) and 63% in those with
      advanced tumors (T3 and T4). The overall five-year determinate survival rates of
      the RT-only group and the postoperative RT group were 90% and 57%, respectively.
      In patients with advanced tumors (stages III and IV), survival rates were
      comparable for RT alone and postoperative RT (56% and 52%, respectively).

PMID- 7808202
TI  - Immunizations for the elderly.

PMID- 7808203
TI  - A clinical moment with endocrinology and metabolism. Early breast development in
      female children.

PMID- 7808204
TI  - Imaging case of the month. Pulmonary lymphangitic carcinomatosis from
      adenocarcinoma of the prostate.

PMID- 7808205
TI  - A plan for medical liability reform. Position statement of the American
      Association of Neurological Surgeons, Congress of Neurological Surgeons, and
      Joint Council of the State Neurosurgical Societies.

PMID- 7808206
TI  - Comparison of the rating scale and the standard gamble in measuring patient
      preferences for outcomes of gallstone disease.
AB  - To estimate patient preferences for gallstone-related treatments and outcomes,
      and assess how preferences vary by patient characteristics and scaling technique,
      the authors randomly assigned 40 patients without gallstones to interviews based
      on a rating scale (n = 22) and a standard gamble (n = 18). The patients assigned
      preference values (possible values 0 to 1) to open cholecystectomy (mean 0.45 by
      rating scale, 0.78 by standard gamble), laparoscopic cholecystectomy (0.71,
      0.91), extracorporeal shock-wave lithotripsy (0.77, 0.89), acute cholecystitis
      (0.36, 0.77), lifetime biliary colic (0.41, 0.71), postcholecystectomy syndrome
      (0.43, 0.79), asymptomatic stone necessitating treatment with bile acids (0.76,
      0.96), and surgical scar (0.79, 0.998). Preferences varied little by age, gender,
      or race. Standard gamble values were highly correlated with, but significantly
      greater than, rating scale values. The authors conclude that patients'
      preferences for gallstone-related conditions generally are significantly less
      than one, and differ markedly by the scaling technique used to derive them. These
      results should be considered when patient preferences are incorporated into
      analyses of gallstone treatments.

PMID- 7808207
TI  - The costs and benefits of a screening program to detect dementia in older
      drivers.
AB  - A Markov model was used to assess the cost-benefit ratios of six strategies of
      screening older drivers for mental status, beginning at age 65. Probabilities of
      motor vehicle collisions (MVCs), injuries, and fatalities were obtained from
      national data. Dementia prevalence, test characteristics, and costs were obtained
      from the literature. Costs included lost wages, car ownership, alternative
      transportation, and injuries. Using a relative risk of MVC for those with
      dementia of 5 and a 5% annual discounting rate, the average cost per driver
      ranged from $51,600 (no testing) to $58,400 (testing every five years). The
      benefit was < one day of life gained, and the benefits of screening cost
      approximately 2.8 million dollars per life-year gained. Increasing the relative
      risk from 5 to 20 substantially improved the cost-benefit of mental status
      screening. However, mental status screening of older drivers would also be cost
      beneficial if physician referral costs were lowered to $60 per evaluation. The
      authors conclude that a dementia screening program for older drivers would be
      cost-beneficial if physician evaluations were limited or their cost lowered to <
      or = $60.

PMID- 7808208
TI  - An economic analysis of strategies for the use of contrast media for diagnostic
      cardiac catheterization.
AB  - A decision tree model was used to estimate the incremental cost per quality
      adjusted life year (QALY) of low- as opposed to high-osmolality contrast media
      for cardiac angiography. Analyses were done from the viewpoints of a third-party
      payer and society using data from a randomized trial and the literature. Assuming
      low-osmolality media reduce the risk of myocardial infarction and stroke, the
      incremental cost per QALY gained with these media is $17,264 in high-risk or
      $47,874 in low-risk patients for a third-party payer. From a societal viewpoint,
      the corresponding costs are $649 and $35,509. These estimates are sensitive to
      the cost and volume of the contrast medium employed and to the estimate of
      reduction in severe adverse events with low-osmolality media. The authors
      conclude that, in the context of restricted budgets, limiting the use of low
      osmolality media to high-risk patients is justifiable, as the incremental cost
      per QALY in high-risk patients may be reasonable and it is not certain that low
      osmolality media prevent severe or fatal events. A considerable reduction in the
      cost per QALY gained is possibly by minimizing the volume of contrast medium
      used.

PMID- 7808209
TI  - Where are the non-visiting patients?
AB  - In a clinical trial to increase the screening of inner-city women for breast
      cancer, some preliminary data suggested that about 40% of the age-eligible women
      who had been patients at a primary-care clinic might be expected never to visit
      that clinic again. The distribution of time between patients' clinic visits was
      modeled by fitting a distribution function to data on the "time to first visit,"
      and indicated that the true defection rate is probably around 31 to 36%. This
      result, which is consistent with four related observations, suggests that most of
      the patients who fail to visit their clinics in a year-long interval may have
      become clients of other clinics. This conjecture implies massive continuing
      exchanges of patients among clinics, and may mean that explicit outreach by mail
      or phone to "non-visiting clients" will add few patient contacts to those based
      on spontaneous clinic visits.

PMID- 7808210
TI  - Designing a simpler high blood cholesterol case detection strategy: are the
      advantages of the NCEP protocol worth the complexity?
AB  - OBJECTIVE: To determine whether the complex strategy of lipid measurements for
      the detection of patients with high blood cholesterol levels proposed by the
      first Expert Panel of the National Cholesterol Education Panel (NCEP) could be
      simplified without significant loss of accuracy. DESIGN: Decision-analysis-based
      model of competing case detection strategies as compared with the NCEP strategy.
      A Markov model was used to estimate numbers of people treated over ten years as a
      result of the different classification strategies. DATA SOURCES: Conditional
      probabilities for the decision trees were derived from cholesterol distributions
      in national population-based surveys. Parameters for the Markov model were from
      published major epidemiologic studies and clinical trials. MAIN OUTCOME MEASURES:
      Misclassification to treatment vs non-treatment as a continuous function of the
      distribution of true low-density lipoprotein (LDL). RESULTS: A simplified
      strategy was designed that screens high-risk persons with two LDL measurements
      and low-risk people with one cholesterol measurement followed by two LDL
      measurements if the initial value is high. This algorithm requires 37% fewer
      measurements to classify a population. The overall accuracy of classification to
      treatment based on the NCEP I cutoff points is high, with a positive predictive
      value of 95% and a negative predictive value of 87% (relative to 97% and 80%,
      respectively, for the NCEP I protocol). This strategy is very similar to
      published NCEP II guidelines. A strategy that recommends an LDL determination for
      everyone, as a recent NIH consensus panel suggested, also significantly reduces
      the number of measurements required by 48%. The positive predictive value is 93%,
      vs 97% for the NCEP I protocol. The negative predictive value is 92%, vs 80% for
      the NCEP I. CONCLUSIONS: The complex measurement strategy initially proposed in
      the NCEP I guidelines did not improve accuracy of classification over the simpler
      and more convenient strategies that the authors evaluated and that have been
      substantially adopted in the NCEP II guidelines.

PMID- 7808211
TI  - Assessing disease prevalence from inaccurate test results: teaching an old dog
      new tricks.
AB  - Estimates of disease prevalence are needed for the interpretation of test results
      as well as for public health decisions. Assessing prevalence may be difficult if
      a definitive test is unavailable, impractical, or expensive. A formula derived
      from Bayes' theorem can calculate the prevalence of disease in a population by
      incorporating test results with a knowledge of the sensitivity and specificity of
      a test. This paper reviews this formula and provides examples evaluating the
      prevalence of HIV disease, the usefulness of ventilation-perfusion scans in
      diagnosing pulmonary embolism, and settings where screening tests should not be
      applied. These examples demonstrate that precise yet inexpensive estimates of
      disease prevalence are possible by enhancing the usefulness of an inaccurate
      test.

PMID- 7808212
TI  - ROC curves and the areas under them for dichotomized tests: empirical findings
      for logistically and normally distributed diagnostic test results.
AB  - Many measures, including sensitivity and specificity, predictive values, and
      likelihood ratios, are available for the assessment of diagnostic tests. A
      drawback of the use of these measures is that continuous test results are often
      dichotomized, with consequent loss of information. Receiver operating
      characteristic (ROC) curves do not depend on discrimination thresholds, and
      therefore the area under the ROC curve (AUC) is one of the preferred measures.
      Although quantitative test results are often presented dichotomized, it would be
      convenient still to be able to estimate the ROC curve and the AUC. The authors
      present equations for such estimates when only one pair of a true- and a false
      positive rate is given, for inherently logistically and normally distributed
      data. Illustrative empirical data are provided for both distributions. In
      contradiction to earlier reports, the authors also show that differential disease
      verification may skew the ROC curve. The ROC curve is thus not invariant to
      selection bias.

PMID- 7808213
TI  - A method for estimating the cost-effectiveness of incorporating patient
      preferences into practice guidelines.
AB  - Many clinical practice guidelines fail to account for the preferences of the
      individual patient. Approaches that seek to include the preferences of the
      individual patient in the decision-making process (e.g., interactive videodisks
      for patient education), however, may incur substantial incremental costs.
      Developers of clinical practice guidelines must therefore determine whether it is
      appropriate to make their guidelines flexible with regard to patient preferences.
      The authors present a formal method for determining the cost-effectiveness of
      incorporating the preferences of individual patients into clinical practice
      guidelines. Based on utilities assessed from 37 patients, they apply the method
      in the setting of mild hypertension. In this example, they estimate that the cost
      effectiveness ratio for individualized utility assessment is $48,565 per quality
      adjusted year of life, a ratio that compares favorably with other health
      interventions that are promoted actively. This approach, which can be applied to
      any clinical domain, offers a formal method for determining whether the
      incorporation of individual patient preferences is important clinically and is
      justified economically.

PMID- 7808214
TI  - p(C) analysis facilitates dementia diagnosis.
AB  - A modified receiver operating characteristic (ROC) analysis technique was applied
      to a sample of 161 consecutive volunteers seen in a dementia clinic. Clinical,
      imaging, neuropsychological, and laboratory evaluation guided experienced
      clinicians in clinical diagnosis, taken as the "gold standard." Two symptom
      inventories, the Hachinski Ischemic Score and the Dementia of the Alzheimer's
      Type Inventory, were obtained by clinicians who were blind to final clinical
      diagnosis; scores on these inventories correlate with the likelihoods of multi
      infarct dementia and Alzheimer's disease, respectively. A disjunctive sequential
      testing strategy was analyzed such that subthreshold scores on the first test
      identified patients for whom the second test was considered. Both tests were
      analyzed at all possible cutoff-point combinations and in both possible testing
      sequences. Diagnoses based on these tests were compared with the clinical "gold
      standard" diagnoses to determine the accuracy of the testing procedures. The best
      strategy correctly classified 154/161 (95.6%) of the dementia patients and
      required cutoff points (5 for the HIS and 10 for the Dementia of the Alzheimer's
      Type Inventory) that were lower than those usually recommended for either test
      used alone (i.e., 7 and 14, respectively). The Hachinski Ischemic Score--then
      Dementia of the Alzheimer's Type Inventory testing sequence was superior to the
      reverse strategy. A sensitivity analysis (varying prevalences of Alzheimer's
      disease, multi-infarct dementia, and other dementias) revealed similar test
      performances across a wide range of prevalences. These data suggest that simple
      clinical tests that take approximately 30 minutes to administer can produce
      diagnostic classifications of dementia that are similar to those of clinicians
      experienced in dementia diagnosis.

PMID- 7808215
TI  - The influence of education and experience on ethical attitudes in neonatal
      intensive care.
AB  - A cross-sectional survey of medical students, pediatrics residents, and
      neonatologists attempted to identify the combined influence of education and
      experience on ethical attitudes regarding the management of infants weighing less
      than 750 g at birth. Of the 120 people surveyed, 94 (78%) returned usable
      surveys. All groups rated quality of life the most important criterion in
      treatment decisions. Conversely, cost was rated least important by each group. In
      addition, cost was rated relatively more important by the clinical medical
      students than by the preclinical students, residents, or neonatologists. The
      neonatologist was rated the most important decision maker by the neonatologists
      and the residents. The parents were rated most important by both groups of
      students. Severe mental retardation was regarded as an unacceptable quality of
      life by 82% of the neonatologists, 63% of the residents, 61% of the clinical
      students, and 48% of the preclinical students. Severe cerebral palsy was
      considered an unacceptable quality of life by 73% of the neonatologists, 63% of
      the residents, 50% of the clinical students, and only 32% of the preclinical
      students. Finally, the anticipated long-term outcome of extremely-low-birth
      weight infants was viewed more positively by the neonatologists than by the other
      groups surveyed.

PMID- 7808216
TI  - Novel cDNA clones obtained by antibody screening of a mouse cerebellar cDNA
      expression library.
AB  - In order to obtain cDNAs of genes that are expressed in cerebellar granule cells
      (GC), an antiserum was raised against GC isolated from mouse cerebella. Western
      blot analysis demonstrated that antibodies against multiple proteins were present
      and immunohistochemical analysis showed that at least some of these proteins were
      localized to cerebellar GC. The antiserum was used to screen an expression
      library derived from mouse cerebellar cDNA. Twenty-two granule cell antibody
      positive (GCAP) clones were obtained. Of these, eight represented genes
      previously described and 14 were novel clones (not found in the GenBank
      database). In situ hybridization histochemistry showed that eight of the novel
      clones had moderate to strong expression in cerebellar GC and some of these
      clones were expressed also in the hippocampal formation. One such clone, GCAP-7,
      appears to represent a single-copy gene and the entire cDNA insert (2,688 bp) has
      been sequenced. The clone appears to consist primarily of the 3' untranslated
      portion, including a poly(A) tail and polyadenylation signals, of a 5 kb
      transcript. The GCAP clones should be useful for future studies of molecular
      biology of GC in normal individuals and in inherited neurologic disease with GC
      degeneration.

PMID- 7808218
TI  - Differential expression of GABAA receptor subunit mRNAs in ethanol-naive
      withdrawal seizure resistant (WSR) vs. withdrawal seizure prone (WSP) mouse
      brain.
AB  - Several lines of evidence suggest an important role for ethanol interactions with
      GABAA receptors in the development of the ethanol withdrawal syndrome. The
      present study was undertaken to determine whether there is a genetic relationship
      between ethanol withdrawal seizure severity and the expression of particular
      GABAA receptor subunits in mouse lines selectively bred for differential
      sensitivity to ethanol withdrawal seizures. Since GABAA receptor subunit levels
      are subject to modulation by ethanol, the levels of GABAA receptor alpha 1, alpha
      6 and beta 2 subunit mRNAs were measured in cerebellum while alpha 1 and beta 2
      subunit levels were determined in cerebral cortex of ethanol-naive WSR and WSP
      mice. Poly(A)+ RNA was isolated from groups of 6-10 animals and the GABAA
      receptor subunit mRNA levels were quantified by Northern blot analysis using
      subunit selective cRNA probes. In the cerebellum, greater levels of each of these
      subunit mRNAs were detected in WSR1 mice compared to WSP1 mice. The levels of
      GABAA receptor alpha 1 subunit mRNAs were approximately 26 +/- 16 percent greater
      for the 4.4 kb transcript and 84 +/- 23 percent greater for the 4.8 kb transcript
      in WSR mice vs WSP mice. GABAA receptor alpha 6 subunit (2.7 kb) mRNA levels in
      cerebellum were 159 +/- 58 percent greater in WSR mice than WSP mice, while beta
      2 subunit mRNA levels were 110 +/- 30 percent greater in WSR than WSP mice. These
      results were replicated for the alpha 1 and alpha 6 subunits in WSR2 vs WSP2
      mouse cerebella. No differences in beta-actin mRNA levels were detected on the
      same RNA blots.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7808217
TI  - Molecular characterization of a novel cDNA from murine cerebellum, developmental
      expression, and distribution in brain.
AB  - Several novel cDNA clones were previously identified by immunoscreening a
      cerebellar cDNA expression library derived from heterozygous weaver (wu/+) mice
      at postnatal day one (P1) with an antigranule cell antiserum. One cDNA, GCAP-8
      (granule cell antiserum-positive clone 8) has been further characterized. The 1.1
      kb insert is a partial cDNA containing a segment near the 3' end of the full
      length cDNA. The 5' end of the GCAP-8 cDNA contains a 259 nucleotide open reading
      frame (ORF) coding for the last 85 amino acids of the carboxy terminus of the
      encoded protein. The encoded polypeptide contains two highly hydrophobic segments
      interrupted by a basic stretch. The carboxy terminus of this protein is cysteine
      rich, with 10 cysteine residues among the 85 amino acids. The GCAP-8 cDNA
      probably represents a single-copy gene. The GCAP-8 gene, designated Gcap1, was
      mapped to the distal region of mouse chromosome 5 by the analyses of two
      multilocus crosses. The distribution of the GCAP-8 mRNA in mouse brain was
      studied by in situ hybridization histochemistry. In the adult mouse brain, strong
      hybridization was detected in cerebellum, hippocampus, substantia nigra (SN), and
      cerebral cortex. In mouse cerebellum, hybridization was detected in granule
      cells, Purkinje cells, and in cells of the deep cerebellar nuclei (DCN). In human
      cerebellum, hybridization was detected in the granule cell layer. In the mouse,
      GCAP-8 is expressed at least as early as embryonic day 14 (E14) in the central
      nervous system (CNS).

PMID- 7808219
TI  - Regulation of NMDA receptor subunit mRNA expression in the rat brain during
      postnatal development.
AB  - Different NMDA receptor subunits have been recently cloned. The present paper
      describes the developmental profile of expression of the NR-1 subunit and three
      NR-2 subunits (A, B, C) in the rat central nervous system. A sensitive RNase
      protection assay was employed to determine simultaneously the mRNA levels of
      these receptor subunits. We found low levels of NR-1 mRNA (comprising all
      different splicing isoforms) in newborn rats with a progressive increase of its
      expression in the following 2-3 weeks. NR-2 subunits can be regarded as
      'modulatory' since their expression can produce differences in the properties of
      NMDA receptors. More than one NR-2 subunits can be expressed in the same brain
      region. NR-2A and NR-2C are concomitantly expressed in the cerebellum and during
      development their mRNAs increase with a similar profile from low levels in P-8
      rats to maximal expression in P-21 animals. NR-2A and NR-2B are concomitantly
      expressed in several brain regions with a different ontogenetic profile. In the
      hippocampus NR-2B mRNA increases rapidly during the first week of life as
      compared to the NR-2A subunits which at this time is expressed to low levels
      indicating that NR-2B will probably be dominant in determining the NMDA
      properties during the first period of life. Our data can provide a molecular
      correlate with properties of NMDA receptors such as voltage dependent Mg2+ block
      and deactivation kinetics which undergo significant changes during development
      and have been shown to depend upon the NR-2 subunit co-expressed with the common
      NR-1 subunit in various brain regions.

PMID- 7808220
TI  - Electroconvulsive seizures upregulate astroglial gene expression selectively in
      the dentate gyrus.
AB  - Previous studies have revealed that kindled seizures induced via chronically
      implanted electrodes up-regulate the expression of glial fibrillary acidic
      protein (GFAP), the protein constituent of intermediate filaments in astrocytes.
      The present study evaluates the consequences of a single electroconvulsive
      seizure (ECS) on glial gene expression. ECS were induced in mice via externally
      placed electrodes. GFAP mRNA levels were evaluated 1, 2, 4, and 6 days post
      seizure by in situ hybridization. GFA immunocytostaining was evaluated in a
      separate series of animals. Following a single ECS, the levels of mRNA for GFAP
      increased several fold by 1 day and were still substantially elevated at 4 days.
      The increases occurred primarily in the dentate gyrus despite the fact that the
      seizures involved widespread brain regions. GFAP mRNA levels were also increased
      in areas bordering the ventricles, especially in areas immediately adjacent to
      the dentate gyrus. These results indicate that ECS up-regulates the mRNA for a
      key structural protein of astrocytes in a manner that is similar to the response
      that occurs following injury, that this response occurs selectively in a part of
      the brain that plays a key role in memory function, and that the increase may be
      due in part to a diffusible substance that also affects glial gene expression in
      nearby structures.

PMID- 7808221
TI  - Molecular characterization of type I GABAA receptor complex from rat cerebral
      cortex and hippocampus.
AB  - The molecular composition of the native gamma-aminobutyric acidA (GABAA) receptor
      complex is actually unknown. In the present communication we report a novel
      approach to characterize the minimal molecular conformation of the native GABAA
      receptor complex. This novel approach is based on the combination of subunit
      specific antibodies and specific 3H-labeled ligands in immunoprecipitation
      experiments. We have determined the presence of beta 2/3 and gamma 2 subunits in
      the Type I GABAA receptor complex, from rat cerebral cortex and hippocampus, by
      using two antibodies, the monoclonal 62-3G1 (specific for beta 2/3) and the
      polyclonal anti-gamma 2 (to the large intracellular loop of the gamma 2 short
      form) together with the Type I-specific ligand [3H]zolpidem. The association of
      gamma 2 and beta 2/3 subunits with the GABAA receptor complex was also tested
      using [3H]flumazenil. The results indicated that both gamma 2 and beta 2/3 were
      the most abundant subunits associated to either Type I or total benzodiazepine
      receptors from both cortex and hippocampus. Between 70-80% of Type I or total
      benzodiazepine binding activity was immunoprecipitated by either antibody. In
      addition, we have also investigated the coexistence of both subunits as part of
      the same population of Type I GABAA receptor complex by cross-immunoprecipitation
      experiments with 62-3G1 and anti-gamma 2. The results indicated that, in cerebral
      cortex, both gamma 2 and beta 2/3 subunits were part of the same population of
      Type I receptors. In hippocampus, an additional 20% of Type I receptors displayed
      either gamma 2 or beta 2/3 but not both subunits.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7808222
TI  - Induction of multiple immediate early genes in rat hypothalamic paraventricular
      nucleus after stress.
AB  - We have previously demonstrated that stress causes a rapid and transient
      elevation in the expression of the immediate early genes (IEGs) c-fos and the
      members of the jun gene family in the brain. Here we demonstrate the effect of
      stress on the expression of fra-1, fra-2 and recently characterized IEGs encoding
      zinc finger containing proteins. Capsaicin-induced stress caused a rapid and
      transient induction of NGFI-A, NGFI-B, fra-2 and TIS11 in the hypothalamic
      paraventricular nucleus. The NGFI-A mRNA levels were also slightly increased in
      the cerebral cortex and striatum. The expression of fra-1, NGFI-C, egr-3 and
      Nurr1 did not show any change. The time course of the induction of NGFI-A, NGFI
      B, fra-2 and TIS11 was similar to that previously observed with c-fos and the
      members of the jun family. The present results suggest that NGFI-A, NGFI-B, fra-2
      and TIS11 mediate some of the stress-induced changes of the PVN at the level of
      gene expression. Although the genes of the NGFI/egr family encode structurally
      similar proteins, they seem to be regulated differentially and thus have diverse
      roles in regulating gene expression in the brain.

PMID- 7808223
TI  - NGF mRNA is not decreased in frontal cortex from Alzheimer's disease patients.
AB  - Alzheimer's disease (AD) is characterized by neuronal dysfunction and
      degeneration in certain brain regions such as cortex, hippocampus and basal
      forebrain. Specific neurochemical defects such as decreases in cholinergic
      enzymes and in the amounts of mRNA in AD brain have also been reported. Nerve
      growth factor (NGF), a protein necessary for the development, regulation and
      survival of basal forebrain cholinergic neurons (BFCN), is synthesized in target
      areas of BFCN (cortex, hippocampus) and is supplied to BFCN by retrograde
      transport. Thus, NGF is under investigation both as a potential therapeutic agent
      and for its possible involvement in the pathogenesis of AD. In this study,
      postmortem brain tissues from both control and AD cases were investigated for
      amounts of poly (A)+ mRNA and NGF mRNA in the frontal cortex, a region rich in
      cholinergic afferents. Yields of poly(A)+ mRNA were similar from normal and AD
      tissues. Human NGF mRNA comigrated with murine NGF mRNA on Northern blots.
      Additionally, dot blot quantitation demonstrated that NGF mRNA levels do not
      differ in the inferior frontal gyrus of normal and AD patients. Thus, we conclude
      that levels of mRNA in general, and of NGF mRNA in particular, are unchanged in
      the frontal cortex of individuals affected by AD.

PMID- 7808224
TI  - CNTF receptor alpha mRNA expression in rodent cell lines and developing rat.
AB  - Ciliary neurotrophic factor (CNTF) has been shown to modulate the in vitro and in
      vivo survival, proliferation and differentiation of many neuronal cell types.
      Evidence indicates that it produces most if not all these effects by binding to a
      receptor subunit referred to as the CNTF receptor alpha component (CNTFR alpha).
      We cloned a cDNA encoding part of the rat CNTFR alpha and used it in Northern
      analyses to study CNTFR alpha mRNA expression. Examination of various tissues of
      embryonic day 18 and postnatal day 14 rats indicated that CNTFR alpha mRNA is
      primarily but not exclusively expressed in brain at these stages of development.
      Further studies revealed that the CNTFR alpha transcripts are present throughout
      brain development from embryonic day 12 to adulthood and display a widespread
      distribution in the adult brain. A survey of rodent cell lines detected highest
      CNTFR alpha mRNA concentrations in neuronal lines and a low concentration in a
      Schwann cell derived line. CNTFR alpha mRNA was not detected in fibroblast lines
      and a glioma line. Finally, nerve growth factor treatment decreased CNTFR alpha
      mRNA levels in PC12 cells. This result demonstrates that signal transduction
      processes activated by a neurotrophin can influence CNTF activated signal
      transduction processes. Such cross-talk may play an important in vivo role in the
      development and maintenance of the many neuronal cell types that are responsive
      to both neurotrophins and CNTF.

PMID- 7808225
TI  - The amino acid residues 1-128 in the alpha subunit of the nicotinic acetylcholine
      receptor contain assembly signals.
AB  - Expression of nicotinic acetylcholine receptor (AChR) involves complex processes
      including assembly of different receptor subunits into hetero-oligomers. To
      identify the minimal N-terminal region involved in AChR subunit association, we
      used a dominant negative assay. Co-expression of fragments of the alpha subunit,
      containing the N-terminal extracellular domain and transmembrane domain 1 (TM 1),
      with the parental AChR subunits in Xenopus oocytes blocked functional expression
      of the receptor. In contrast, co-expression of N-terminal extracellular fragments
      without TM1 failed to inhibit functional expression of AChRs, but altered the
      functional properties of co-expressed parental AChRs. Furthermore, when these
      alpha subunit fragments were co-expressed with the beta, gamma, and delta
      subunits, they were co-immunoprecipitated with a mixture of beta, gamma, and
      delta subunit specific antibodies. These results suggest that 'assembly signals'
      are confined to a local structure in the N-terminal extracellular domain. Our
      findings also indicate that an assembly step may be a target for genetic
      intervention not only to block the expression of functional receptors, but also
      to alter the function of the receptor.

PMID- 7808226
TI  - Elevated insulin-like growth factor (IGF) gene expression in sciatic nerves
      during IGF-supported nerve regeneration.
AB  - Nerve regeneration is augmented by neurotrophic activity, which has long been
      known to be increased in lesioned nerves. Of identified soluble nerve-derived
      neurotrophic factors, to date only insulin-like growth factors (IGFs) have been
      observed to increase the rate of axon regeneration in peripheral nerves. We
      report that IGF-I and IGF-II mRNA contents were significantly increased (P <
      0.0005) distal to the site of crush in rat sciatic nerves, and decreased
      following axon regeneration. In transected nerves in which axon regeneration was
      prevented, IGF mRNAs remained elevated. IGF-I mRNAs per mg tissue were increased
      more in lesioned nerves than denervated muscles, whereas IGF-II mRNAs were
      increased more in denervated muscles than lesioned nerves. This suggested that
      IGF-I and IGF-II each play distinct regulatory roles during regeneration. These
      data bolster the hypothesis that increased IGF mRNA content in nerves supports
      the rate of nerve regeneration in mammals.

PMID- 7808227
TI  - Developmental changes in GAP-43 expression in primary cultures of rat cerebellar
      granule cells.
AB  - GAP-43 is a growth-associated protein that has been implicated in the
      developmental outgrowth of axons. We have examined the profile of GAP-43 levels
      in rat cerebellar granule cells during their development in vitro. During the
      first 1-2 days after plating, the majority of cells expressed neurites and after
      8 days a complex neuronal network had developed. In situ hybridization studies
      showed that GAP-43 mRNA levels rapidly increased to peak at 1-2 days and
      gradually returned to initial values after 7-8 days. Analysis of GAP-43 protein
      levels followed a similar transient profile. Initially, granule cell perikarya
      and structures associated with neuritogenesis all displayed GAP-43
      immunoreactivity. In older cultures, perikaryal labelling was lost after 10 days
      whilst process staining decreased more gradually. During the first 48 hours
      detailed analysis of GAP-43 mRNA revealed two populations of granule cells. It
      was suggested that cells with significant label originated from the external
      germinal layer which displays much GAP-43 mRNA in cerebellar sections. Cells with
      little or no GAP-43, however, probably originated from the internal granular
      layer since this region displayed no specific labelling. Granule cells within
      clumps expressed more GAP-43 mRNA compared to isolated cells perhaps indicating
      cell-cell regulation of expression. These results describe the transient rise in
      GAP-43 protein and mRNA levels expressed by developing cerebellar granule cell
      neurons in vitro and provide further evidence for the role GAP-43 plays during
      neuritogenesis.

PMID- 7808228
TI  - Transcripts encoding a neural membrane CD26 peptidase-like protein are stimulated
      by synaptic activity.
AB  - We isolated a cDNA clone, named BSPL, that encodes a brain-specific dipeptidyl
      peptidase-like protein with 30% identity and 50% similarity to CD26, a lymphocyte
      membrane antigen involved in T-cell activation. BSPL lacks, however, the
      catalytic residue responsible for peptidase activity. The expression of BSPL is
      widespread throughout the CNS but restricted to neurons under normal conditions.
      Twenty-four hours after injection of kainic acid into the hippocampus, a dramatic
      increase in the concentration of BSPL mRNA was detected by in situ hybridization
      in the CA3 region of the injected hemisphere as compared with the contralateral
      hemisphere or sham-injected animals. An increase in the steady-state level of
      BSPL mRNA concentration was also found following tetanic stimulation of the
      perforant path to produce LTP in granule cells of the dentate gyrus.
      Hybridization signals could be detected in dendritic processes of pyramidal
      neurons and in some glial cells upon either type of stimulation. These data
      suggest that BSPL may be involved in synaptic plasticity.

PMID- 7808229
TI  - Inhibition of protein kinase C- and casein kinase II-mediated phosphorylation of
      GAP-43 by S100 beta.
AB  - The effect of the glial-derived protein, S100 beta, on the in vitro
      phosphorylation of the growth-associated protein GAP-43 was investigated. S100
      beta inhibited in a dose dependent manner the phosphorylation of GAP-43 by
      protein kinase C (PKC) or by casein kinase II (CKII). S100 beta appeared to slow
      down the rate and the degree to which GAP-43 can be phosphorylated by either
      kinase. The specificity of the inhibition was demonstrated by the observation
      that the phosphorylation of two other CKII substrates, casein and a selective
      peptide substrate, was not inhibited by S100 beta. The marked inhibitory effect
      of S100 beta required the presence of calcium in the phosphorylation reactions.
      In addition, S100 beta inhibition of GAP-43 phosphorylation was seen with GAP-43
      purified under a variety of conditions that alter acylation, suggesting that the
      acylation state of GAP-43 does not affect the ability of S100 beta to modulate
      CKII- or PKC-mediated phosphorylation of GAP-43.

PMID- 7808230
TI  - GLUT1 and GLUT3 gene expression in gerbil brain following brief ischemia: an in
      situ hybridization study.
AB  - GLUT1 and GLUT3 mRNAs in normal and post-ischemic gerbil brains were examined
      qualitatively and semi-quantitatively using in situ hybridization in conjunction
      with image analysis. Coronal brain sections at the level of the anterior
      hippocampus were prepared three hours, one day, and three days after animals were
      subjected to six min of ischemia. The sections were hybridized with vector- and
      PCR-generated RNA probes labeled with 35S. Microscopic evaluation of hybridized
      brain sections coated with autoradiographic emulsion indicated that GLUT1 mRNA
      was associated with brain microvessels, choroid plexus, and some ependymal cells.
      GLUT1 mRNA was not observed in neurons, except that one day following ischemia,
      this mRNA was induced in neurons of the dentate gyrus. GLUT3 mRNA was detected
      only in neurons. Image analysis of film autoradiograms revealed that both the
      GLUT1 and GLUT3 messages increased following ischemia but returned nearly to
      control levels by day three. In the CA1 region of the hippocampus the increase in
      GLUT3 mRNA was not statistically significant, and by day three the level had
      fallen significantly below the control, coinciding with the degeneration of the
      CA1 neurons. Our results suggest that the brain possesses mechanisms for
      induction and up-regulation of glucose transporter gene expression.

PMID- 7808231
TI  - Lactation-induced deficits in NMDA receptor-mediated cortical and hippocampal
      activation: changes in NMDA receptor gene expression and brainstem activation.
AB  - During lactation, there is an inhibition of cortical and hippocampal activation
      in response to N-methyl-D,L-aspartate (NMA), but not kainate, as assessed by
      induction of c-Fos expression. To study whether changes in NMDA receptor function
      may account for this inhibition, NMDA receptor subunit (NMDAR1) mRNA levels were
      measured by both Northern analysis and in situ hybridization. Analysis of NMDAR1
      gene expression by Northern blot analysis did not reveal significant differences
      between cycling and lactating rats. Using in situ hybridization, NMDAR1 mRNA
      levels in several cortical and hippocampal areas appeared to be smaller in
      lactating rats, compared to cycling rats, although these differences reached
      significance only in the fronto-parietal cortex and piriform cortex. These subtle
      changes in NMDAR1 receptor subunit gene expression during lactation are not
      likely to account for the global lack of neuronal activation in response to NMA.
      However, it is possible that there may be changes in other NMDA receptor subunits
      that could account for the deficits in NMDA receptor activation. We also examined
      the activation state of afferent pathways in the brainstem that provide
      excitatory input to the cortex and hippocampus. During lactation, NMA induced c
      Fos expression in similar areas of the brainstem as during the cycle, except in
      the locus coeruleus and dorsal raphe, where c-Fos expression was significantly
      less than that observed during the cycle. In contrast, no differences in the
      pattern of c-Fos expression in the brainstem in response to kainate were observed
      between cycling and lactating rats. The lack of NMA-induced activation of the
      locus coeruleus and dorsal raphe may contribute to the lack of cortical
      activation during lactation.

PMID- 7808232
TI  - Differential effects of dopamine depletion on the binding and mRNA levels of
      dopamine receptors in the shell and core of the rat nucleus accumbens.
AB  - In the present study, using quantitative receptor autoradiography and in situ
      hybridization histochemistry the effects of unilateral 6-hydroxydopamine lesions
      on the binding density levels of dopamine D1 and D2 receptors and the levels of
      mRNA encoding D1 and D2 receptors were investigated in the core and shell
      territories of the nucleus accumbens (Acb) and in the caudate-putamen (CP). The
      lesions induced contrasting effects on the D1 binding and D1 mRNA in the Acb and
      CP, i.e. an increase in binding and a decrease in the mRNA levels. For the D2
      receptor an increase in both the binding density and mRNA levels was observed.
      The lesion-induced effects displayed regional differences. For D1 mRNA and D1 and
      D2 binding, the lesion effect was more pronounced in the core than in the shell
      of the Acb. For the D2 mRNA levels an increase was observed in the CP but not in
      the two territories of the Acb. Furthermore, the decrease in D1 mRNA was greater
      in the rostral than in the caudal parts of the core and shell of the Acb. These
      results indicate that the core and shell of the Acb and the CP respond
      differentially to dopamine depletion.

PMID- 7808233
TI  - Heterogeneous tissue-specific transcription of dopamine receptor subtype
      messenger RNA in rat brain.
AB  - The recent identification through molecular cloning techniques of multiple
      dopamine receptor subtypes has raised interest in the functional interactions
      between some of the newly described receptors and their classic counterparts. The
      dopamine D5 (D1B) receptor gene is of particular interest since there is some
      evidence that its transcriptional tissue distribution is different than that of
      the D1 and D2 receptor genes, possibly implying a unique role for the receptor
      that this gene encodes. This study compares the relative anatomical distribution
      of dopamine D1, D2, and D5 receptor mRNAs in the rat brain using Northern blot
      analysis. The results demonstrate that the patterns of expression for these three
      genes are quite different and tissue specific. Although levels of D1 and D2 mRNA
      are highest in the striatum, levels of D5 mRNA are proportionately much higher in
      the midbrain, hippocampus and hypothalamus. In addition two D5 mRNA transcripts
      were detected in the hippocampus, but not in other brain areas. There were tissue
      specific differences in the size of D5 mRNA transcripts in human brain tissue as
      well. These data may suggest a more specialized role for the dopamine D5 receptor
      within the mammalian brain.

PMID- 7808234
TI  - Glutamate decarboxylase (GAD65) mRNA levels in the striatum and pallidum of MPTP
      treated monkeys.
AB  - The mRNA levels encoding for the enzyme glutamate decarboxylase (GAD65) were
      measured by computerized image analysis after in situ hybridization
      histochemistry in the striatum and pallidum of normal and MPTP-treated squirrel
      monkeys. At striatal level, GAD65 mRNA labeling in MPTP-treated monkeys was
      primarily increased in the dorsolateral sector of the putamen. At pallidal level,
      the intensity of GAD65 mRNA labeling in single neurons was increased in the
      internal but not the external segment of the pallidum of MPTP-treated monkeys.
      The regulation of GAD65 mRNA levels in the striatum and internal segment of the
      pallidum suggest an important role for this enzyme in the regulation of GABAergic
      functions in basal ganglia.

PMID- 7808235
TI  - Structural identification, neuronal synthesis, and role in male copulation of
      myomodulin-A of Lymnaea: a study involving direct peptide profiling of nervous
      tissue by mass spectrometry.
AB  - We used a strategy combining immunodetection, peptide chemistry, and a novel
      method, direct peptide fingerprinting of neurons and small pieces of nerve by
      using matrix-assisted laser desorption ionization mass spectrometry, to
      structurally identify and localize the neuropeptide myomodulin-A in the mollusc,
      Lymnaea stagnalis. Lymnaea myomodulin appeared to be identical to Aplysia
      myomodulin-A and is produced by many central neurons, including neurons located
      in the ventral lobe of the right cerebral ganglion that innervate the penis
      complex via the penis nerve. Myomodulin-A could also be characterized from the
      penis complex, and physiological concentrations of the peptide enhanced the
      relaxation rate of electrically induced contractions of the penis retractor
      muscle in vitro in a dose-dependent fashion.

PMID- 7808236
TI  - Gene transfer and the expression of a foreign gene in vivo in post-mitotic
      neurons of the adult rat brain using the hemagglutinating virus of the Japan
      liposome method.
AB  - Neurons in the adult rat brain were transfected in vivo with a simple plasmid
      that harbored the gene for beta-galactosidase from Escherichia coli under control
      of a chicken beta-actin promoter by use of the hemagglutinating virus of Japan
      (HVJ) and liposomes. Cells that expressed beta-galactosidase were detected only
      in the target area of the central nervous system for 10 days by light microscopic
      analysis. Since electron microscopic analysis revealed that the products of the
      histochemical reaction were predominantly associated with the nuclear membrane
      and the endoplasmic reticulum of positive cells, it appeared that the products
      were translated endogenously and had not been entrapped by endocytosis.
      Furthermore, the products were observed in typical neuronal cells with a large,
      round, and pale nuclei, and with direct axo-somatic and axo-dendritic synaptic
      contacts. This report suggests the possibility of introducing functionally
      significant genes into neurons in targeted areas of the adult central nervous
      system.

PMID- 7808237
TI  - Molecular cloning of rat cDNA for cytosolic phospholipase A2 and the increased
      gene expression in the dentate gyrus following transient forebrain ischemia.
AB  - Rat cytosolic phospholipase A2 (cPLA2) cDNA was cloned from rat brain. The cDNA
      showed a high homology of 90% in the nucleotide sequence of the coding region
      with the human counterpart. By in situ hybridization, the gene expression for
      cPLA2 was detected in the hippocampus, olfactory bulb, and cerebellar granular
      cells at very low level of normal rats. The expression was markedly increased in
      the dentate granule cells of postischemic rat brain. This alteration of the gene
      expression was discussed in relation to the free fatty acid-mediated
      neurotoxicity.

PMID- 7808238
TI  - Psychological components of effort sense.
AB  - The perception of effort is multidimensional and it is governed by many
      physiological, psychological, and experiential factors. This paper deals with a
      discussion of selected psychological states and traits that are known to be
      correlated with the expression of effort sense. It has been shown that anxiety,
      somatic perception, depression, and neuroticism are associated with perceived
      exertion. Extroversion has been found to be inversely correlated with perceived
      exertion, and positively correlated with preferred exercise intensity. These
      empirical findings are congruent with theoretical expectations in each case. It
      has also been found that perception of effort can be increased and decreased in a
      systematic manner with various psychological interventions such as hypnotic
      suggestion, dissociative cognitive strategies, and imagery. Changes in effort
      sense can also be systematically modified by titrating exercise volume (e.g.,
      overtraining, tapering), and this exercise-induced alteration in perception
      covaries with affective changes. The research reviewed in this paper supports the
      conclusion that effort sense is best conceptualized as a complex psychobiological
      construct as originally proposed by Borg three decades ago.

PMID- 7808239
TI  - Perception of breathlessness during exercise in patients with respiratory
      disease.
AB  - The perception of breathlessness during physical activities is a frequent and
      disturbing complaint for patients with chronic respiratory disease.
      Psychophysical principles can be applied to quantitate the severity of dyspnea
      during cardiopulmonary exercise testing. Power production (or work) appears to be
      the most appropriate stimulus for measuring the dyspnea response. The 0-10
      category-ratio (CR-10) scale and the visual analog scale (VAS) are two
      instruments for measuring the intensity of breathlessness. Studies demonstrate
      that the slope and/or intercept of the power production-breathlessness
      relationship provide a valid, reliable, and responsive approach for measurement.
      Ratings of dyspnea during exercise are useful to determine the severity of
      breathing difficulty and to assess the efficacy of therapy.

PMID- 7808240
TI  - Perception of chest pain during exercise testing in patients with coronary artery
      disease.
AB  - Psychophysical scaling of symptoms or discomfort during exercise testing has
      evolved as an important adjunct to the study of therapeutic interventions in
      heart disease. One of the major shortcomings of clinical exercise testing,
      however, has been the assessment of chest pain. Although the presence and
      characteristics of chest pain have important diagnostic, prognostic, and
      therapeutic implications, few studies in the literature adequately address chest
      pain responses to exercise. Clinical trials using exercise as an efficacy
      parameter frequently use only a single descriptive testing endpoint, such as
      "moderate" angina. Methods of scaling chest pain during exercise testing are
      underutilized. Of the several grading systems that have been used, the 0-10 scale
      developed by Borg has been the most common. It is preferable for patients to
      relate chest pain sensations during exercise testing to those experienced during
      daily activities, and treadmill experience improves the reliability and
      reproducibility of patient responses. This paper examines the methodology and
      clinical applications of quantifying chest pain during exercise.

PMID- 7808241
TI  - Prescribing exercise intensity for healthy adults using perceived exertion.
AB  - Rating of perceived exertion (RPE) is endorsed by the American College of Sports
      Medicine as a useful adjuvant for prescribing and monitoring exercise intensity.
      In this paper, I describe a rationale for the use of RPE and other exertional
      symptoms as an alternative to traditional exercise prescription procedures for
      healthy adults. Errors associated with using RPE for producing exercise intensity
      are discussed along with limitations with the use of HRReserve as the standard
      for judging the accuracy of RPE for prescribing relative exercise intensity. The
      concept of preferred exertion is discussed as a prescription paradigm that is
      complementary to the use of perceived exertion and physiological indicators of
      relative exercise intensity. Important areas that have not received enough
      research attention are summarized.

PMID- 7808242
TI  - Clinical and biochemical characteristics of collapsed ultra-marathon runners.
AB  - To evaluate the characteristics of runners with exercise-associated collapse
      (EAC), we studied the time of onset of collapse, rectal temperatures,
      cardiovascular status, and incidence of readily identifiable medical conditions
      in 46 male athletes who collapsed during or after a 56-km ultramarathon footrace
      run on a cool day. Data were compared with 65 control runners who did not
      collapse in the same race. Weight changes during recovery were studied in a
      subsample of both groups. The majority (85%) of runners with EAC collapsed after
      they had completed the race; rectal temperatures (38.5 +/- 1.3 degrees C, mean +/
      SD; range 35.5-42.0 degrees C) and supine heart rates (87.5 +/- 17.2 min-1;
      range 60-138) were only modestly elevated. Postrace serum sodium concentrations,
      changes in plasma volume, and mass during recovery were not significantly
      different from values in control runners. We conclude that: (i) most cases of EAC
      (85%) occur after the finish line; (ii) runners collapsing during the race are
      more likely to have a readily identifiable medical condition than runners
      collapsing after the finish line; (iii) runners collapse most frequently near
      cutoff times for medals and race closure times; and (iv) 16% of EAC casualties
      and 19% of control runners have identifable biochemical abnormalities.

PMID- 7808243
TI  - Effects of exercise intensity, duration, and time of day on fibrinolytic activity
      in physically active men.
AB  - The purposes of this investigation were to determine: 1) whether the fibrinolytic
      responses to acute, submaximal exercise were best related to intensity, duration,
      or total caloric expenditure; and 2) whether the time of day exercise is
      performed affects the fibrinolytic response. Twelve physically active men (mean
      age = 34.8 +/- 4.0 yr) performed four 30-min exercise sessions: 50% VO2max, a.m.
      and p.m., and 80% VO2max, a.m. and p.m. Blood samples were analyzed for tissue
      plasminogen activator (TPA) activity and plasminogen activator inhibitor-1 (PAI
      1) activity. Data were analyzed using a three-way ANOVA with repeated measures.
      TPA activity: preexercise TPA did not differ among the four sessions. TPA
      increased with exercise in all sessions except the 50% a.m. session. Exercise at
      80% increased TPA more than 50% (P < 0.001) and evening sessions increased TPA
      more than morning sessions (P < 0.05). PAI-1 activity: preexercise PAI-1 activity
      was higher during the morning than evening and significantly decreased with
      exercise in all sessions except the 50% p.m. session. It was concluded that
      changes in fibrinolytic activity appear to be influenced primarily by exercise
      intensity rather than duration or total caloric expenditure. Additionally, time
      of day of exercise performance significantly influenced fibrinolytic activity.

PMID- 7808244
TI  - Effects of exercise on the immune response to cancer.
AB  - This study examined the effects of two doses of exercise on tumor incidence and
      progression, and the number and activity of intratumoral phagocytic cells (80%
      macrophages [M phi's]). Male mice were randomly assigned to control (CON),
      moderate (MOD) or exhaustive (EXH) treadmill running. Mice were inoculated
      subcutaneously with 2.5 x 10(5) mammary adenocarcinoma cells after 3 d of running
      (3 h after the last run at a point when enhancement in M phi cytotoxicity is
      observed). This tumor was chosen due to its susceptibility to M phi inhibition in
      vitro and in vivo. Mice continued daily running for 14 d. Food intakes were
      higher during the last 3 d in MOD and EXH, but body weights were no different.
      Flow cytometer analysis of tumor masses revealed that MOD had greater numbers of
      phagocytic cells (vs EXH) with slightly higher phagocytic activities (vs CON and
      EXH) (P < 0.05). However, no group differences in tumor appearance were seen
      except on day 7 when CON had less observable tumors than MOD and EXH (P < 0.05).
      Tumor size was also not different between groups at any point. These results
      indicate that moderate exercise can increase the phagocytic capacity of
      intratumoral phagocytic cells, but these changes had no apparent effect on tumor
      incidence or progression in this study.

PMID- 7808245
TI  - Endurance athletes' stroke volume does not plateau: major advantage is diastolic
      function.
AB  - Left ventricular function was examined during incremental work rates to maximum
      using simultaneous determinations of stroke volume, left ventricular ejection
      time (LVET), and diastolic filling time (DT). Seven endurance trained and seven
      untrained young adult males were studied on a cycle ergometer at matched heart
      rates of 90, 120, 140, 160, 180, and 190 bpm (+/- 1 bpm). Stroke volume of the
      untrained subjects reached a plateau at 120 bpm, but stroke volume of the trained
      subjects continued to increase to their maximum heart rate with no plateau.
      Throughout incremental work rates, LVET was significantly longer and DT was
      significantly shorter in the trained subjects. At a heart rate of 190 bpm, the
      corresponding rates of ventricular emptying and ventricular filling of the
      trained versus the untrained subjects were 20% and 71% greater, respectively (P <
      0.01). We conclude that during incremental work rates the stroke volume of
      endurance trained athletes increases progressively to maximum with no plateau. In
      addition, although trained athletes rely on enhancements in both ventricular
      filling and ventricular emptying to augment stroke volume, by far their major
      advantage over untrained subjects is in ventricular filling.

PMID- 7808246
TI  - Carnitine supplementation: effect on muscle carnitine and glycogen content during
      exercise.
AB  - This study investigated the effects of L-carnitine supplementation on muscle
      carnitine and glycogen content during submaximal exercise (EX). Triglycerides
      were evaluated by a fat feeding (90 g fat) and 3 h later subjects cycled for 60
      min at 70% VO2max (CON). Muscle biopsies were obtained preexercise and after 30
      and 60 min of EX. Blood samples were taken prior to and every 15 min of exercise.
      Subjects randomly completed two additional trials following 7 and 14 d of
      carnitine supplementation (6 g.d-1). During one of the two trials, subjects
      received 2000 units of heparin 15 min prior to EX to elevate FFA (CNhep); no
      heparin was administered during the other trial (CN). There were no differences
      in VO2, respiratory exchange ratio, heart rate, or g.min-1 of CHO and fat
      oxidized among the three trials. At rest serum total acid soluble (TASC) and free
      (FC) carnitine increased with supplementation (TASC; CON, 71.3 +/- 2.9; CN, 92.8
      +/- 5.4; CNhep, 109.8 +/- 3.5 mumol.l-1) (FC; CON, 44.1 +/- 2.7; CN, 66.1 +/-
      5.3; CNhep, 77.1 +/- 4.1 mumol.l-1). During EX, TASC remained stable, while FC
      decreased and short-chain acylcarnitine (SCAC) increased (P < 0.05). Muscle
      carnitine concentration at rest was unaffected by supplementation. During EX,
      muscle TASC did not change, FC decreased, and SCAC increased significantly in all
      three trials. Pre-EX and post-EX muscle glycogens were not different. Increased
      availability of serum carnitine does not result in an increase in muscle
      carnitine content nor does it alter lipid oxidation. It appears that there is an
      adequate amount of carnitine present within the mitochondria to support lipid
      oxidation.

PMID- 7808247
TI  - Effect of exercise training on the onset of type I diabetes in the BB/Wor rat.
AB  - The effects of regular exercise training on the onset and/or severity of
      hyperglycemia were studied in female diabetes-prone Biobreeding/Worcester (DP
      BB/Wor) rats. At 38-39 d of age, animals were weight-matched and randomly
      assigned to exercise-trained (T) and untrained (Unt) groups. The T rats exercised
      on a rodent treadmill at a moderate workload, 5 successive days with the 6th day
      being one of rest. Training lasted 5-11 wk until rats became moribund. Red
      gastrocnemius muscle citrate synthase activity was significantly higher in T
      (54.2 +/- 4.7 mumol.g-1.min-1) compared with Unt (42.9 +/- 5.1). No significant
      difference was found between the T and Unt groups in the following: age at onset
      of hyperglycemia (T = 82.9 +/- 8.7 d; Unt = 82.0 +/- 13.5 d, mean +/- SD),
      ultimate level of hyperglycemia, age of death (T = 89.9 +/- 9.2 d; Unt = 89.4 +/-
      13.9 d), number of days between onset of hyperglycemia and death, or body weights
      at the onset of hyperglycemia. No significant difference was found between groups
      in pancreatic insulin concentration (microgram.g-1 of protein), T = 0.22 +/-
      0.04; Unt = 0.20 +/- 0.34. These data suggest that a program of regular exercise
      training may not delay the onset and/or reduce the severity of hyperglycemia in
      the DP BB/Wor rat. Regular exercise training had no beneficial or detrimental
      effect on pancreatic beta-cell destruction.

PMID- 7808248
TI  - The effect of volume ingested on rehydration and gastric emptying following
      exercise-induced dehydration.
AB  - The purpose of this study was to examine the effects of different drink volumes
      on rehydration, gastric emptying, and markers of fluid balance following exercise
      induced dehydration. Nine male subjects (27.3 +/- 5.47 yr of age, 77.8 +/- 7.9
      kg) exercised for 90 min (or until 2.5% of initial body weight was lost) on a
      cycle ergometer in a hot environment (30 degrees C with 60% RH). Following
      exercise, subjects were moved to a neutral environment (23 degrees C 50% RH) and
      rested for 30 min prior to beginning a 3-h rehydration period. During
      rehydration, subjects were serially fed with an electrolyte solution (14.98
      mmol.l-1 Na+, 13.51 mmol.l-1 Cl-, and 7.95 mmol.l-1 K+) every 30 min with either
      100% or 150% of the fluid lost during exercise. Gastric contents were determined
      every 15 min using double sampling. Blood samples, urine samples, and body
      weights were taken before and after exercise and at 1-h intervals throughout
      rehydration. Blood samples were analyzed for percent change in plasma volume,
      electrolyte concentration, aldosterone levels, and renin activity. Urine
      electrolyte concentrations were also measured. The final percent rehydration was
      48.11 and 67.90 for the 100% and 150% conditions, respectively. During
      rehydration, the subjects emptied 98.9 and 86.0% of the fluid ingested, and the %
      emptied and used for weight gain at the end of rehydration was 55.1 and 54.6 for
      the 100% and 150% trials, respectively. Urine production was significantly higher
      in the 150 compared with the 100% condition while renin and aldosterone levels
      did not differ significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7808249
TI  - Alterations in oxygen consumption during and between bouts of level and downhill
      running.
AB  - Since the etiology of the drift in VO2 during downhill running is unclear, this
      study was designed to assess the contribution of heart rate (HR), ventilation
      (VE), blood lactate, rectal temperature (RT), muscle damage, and several
      variables that have not previously been included in VO2 drift research: muscle
      temperature (MT), and stride rate (SR) and length (SL), to the drift in VO2. Six
      subjects participated in a 45-min level run (LEVEL) and two 45-min downhill runs
      (DOWN1 and DOWN2) at 50% VO2max. Although VO2 increased significantly over time
      for all bouts, the magnitude [4.3% (LEVEL), 5.4% (DOWN1), and 8.1% (DOWN2)] did
      not differ between bouts (P > 0.05). VO2 was significantly lower during DOWN2
      than during LEVEL and DOWN1 (P < 0.05). MT increased during the three bouts (P <
      0.05) but the change over time was not different between bouts. SR and SL did not
      change over time within each bout nor between the two downhill runs. Muscle
      damage, as indicated by serum creatine kinase levels and perceived soreness, was
      less following LEVEL and DOWN2 than DOWN1 (P < 0.05). HR and RT increased over
      time (P < 0.05) but did not differ between bouts. VE and blood lactate did not
      differ over time or between bouts. VO2 drift during the three bouts paralleled
      changes in RT, MT, and HR but appears unrelated to muscle damage or biomechanical
      factors.

PMID- 7808250
TI  - Bilateral performance symmetry during drop landing: a kinetic analysis.
AB  - The assumption that lower extremity function is bilaterally symmetrical is
      prevalent throughout the biomechanics literature. The unilateral development of
      many overuse and acute injuries may suggest that this assumption is inaccurate.
      Analyses of bilateral function report conflicting results and may be partially
      attributable to the types of movement activities utilized and to research
      methodology. The purpose of this study was to evaluate the concurrent bilateral
      performance of the lower extremities during an apparently symmetrical movement
      task. Concurrent left/right side vertical ground reaction forces (VGRF) and lower
      extremity joint moments (JM) were obtained for 10 subjects performing 25
      voluntary hanging drop landings (60 cm) on each of 3 consecutive days. Bilateral
      variability (BV) and systematic bilateral asymmetry (BA) were calculated for each
      trial. Bilateral variability was less for VGRF variables (12.8%) than JM
      variables (25.3%). Bilateral asymmetry was identified more often among VGRF
      variables (52.5%) than JM variables (16.7%). The magnitude of identified BA was
      greater than either the group BV (25%) or BA (110%) and indicates that bilateral
      differences are biomechanically meaningful.

PMID- 7808251
TI  - Fatigue contributes to the strength training stimulus.
AB  - To investigate the role of fatigue in strength training, strength increases
      produced by a training protocol in which subjects rested between contractions
      were compared with those produced when subjects did not rest. Forty-two healthy
      subjects were randomly allocated to either a no-rest group, a rest group, or a
      control group. Subjects in the two training groups trained their elbow flexor
      muscles by lifting a 6RM weight 6-10 times on 3 d each week for 6 wk. Subjects in
      the no-rest group performed repeated lifts without resting, whereas subjects in
      the rest group rested for 30 s between lifts. Both training groups performed the
      same number of lifts at the same relative intensity. The control group did not
      train. Subjects who trained without rests experienced significantly greater mean
      increases in dynamic strength (56.3% +/- 6.8% (SD)) than subjects who trained
      with rests (41.2% +/- 6.6%), and both training groups experienced significantly
      greater mean increases in dynamic strength than the control group (19.7% +/-
      6.6%). It was concluded that greater short-term strength increases are achieved
      when subjects are required to lift training weights without resting. These
      findings suggest that processes associated with fatigue contribute to the
      strength training stimulus.

PMID- 7808252
TI  - Performance decrements with high-intensity resistance exercise overtraining.
AB  - The purpose of this investigation was to study a high-intensity resistance
      exercise overtraining protocol resulting in muscular strength decrements.
      Seventeen weight-trained males were divided into an overtraining group (OT; N =
      11; mean +/- SE, age = 22.0 +/- 0.9 yr,) that exercised on a squat machine daily
      for 2 wk with 100% of 1 repetition maximum (RM) relative intensity, and a control
      group (CON; N = 6; age = 23.7 +/- 2.4 yr) that exercised 1 d.wk-1 with low
      intensity (50% 1 RM). Test batteries were conducted at the beginning (test 1),
      after 1 wk (test 2), and after 2 wk (test 3) of the study. One RM performance
      significantly decreased from test 1 to test 3 (P < 0.05) for the OT group (mean =
      -12.2 +/- 3.8 kg), but not the CON group (mean = -1.1 +/- 0.8 kg). Isokinetic and
      stimulated isometric muscle force significantly decreased for the OT group
      compared with the CON group by test 3. The primary site of maladaptation appeared
      to be in the periphery as indicated by changes in stimulated force, circulating
      CK activity, and exercise-induced lactate responses. This protocol produced a
      significant decrease in 1 RM performance, thus providing a model for the study of
      short-term, high-intensity resistance exercise overtraining.

PMID- 7808253
TI  - Peak oxygen deficit predicts sprint and middle-distance track performance.
AB  - The purpose of this study was to determine the value of the peak oxygen deficit
      (POD) as a predictor of sprint and middle-distance track performance. POD, peak
      blood lactate, VO2peak, lactate threshold, and running economy at 3.6 m.s-1 were
      measured during horizontal treadmill running in 22 male and 19 female competitive
      runners of different event specialties. Subjects also completed running
      performance trials at 100, 200, 400, 800, 1500, and 5000 m. Correlations of track
      performances with POD (ml.kg-1) (-0.66, -0.71, -0.71, -0.62, -0.52, and -0.40)
      were moderately strong at the sprint and middle distances, accounting for 44-50%
      of the performance variance at the three shortest distances. Correlations of
      track performances with peak blood lactate concentration were lower than with POD
      and accounted for approximately one-half as much of the performance variance (21
      26%) at the three shortest distances. Multiple regression analyses indicated that
      the POD was the strongest metabolic predictor of 100-, 200- and 400-m
      performance, and that VO2peak was the strongest metabolic predictor of 800-, 1500
      , and 5000-m performance. We conclude that the POD is a moderately strong
      predictor of sprint and middle-distance track performance.

PMID- 7808254
TI  - Acute weight gain in collegiate wrestlers following a tournament weigh-in.
AB  - The purpose of this study was to determine the magnitude of weight gained in
      collegiate wrestlers between the weigh-in and beginning of tournament
      competition. Body weight of the qualifiers for the NCAA Division I, II, and III
      wrestling finals (N = 668) was recorded at the official weigh-in and again
      approximately 20 h later, before the first round of competition in the
      tournament. The results showed that on average (+/- SD), wrestlers gained 4.9 +/-
      2.4% (3.3 +/- 1.5 kg) of body weight before competing. An inverse relationship
      was found such that wrestlers in the lightest weight classes gained the most
      weight (kg) compared with heavier wrestlers (r = -0.45, P < 0.05). Despite the
      large mean weight gain, the mean discrepancy between first round opponents was
      2.1 +/- 3.0 kg and even less when heavyweight wrestlers were excluded from the
      analyses (1.5 +/- 1.2 kg, N = 607). A significant correlation between weight gain
      and weight discrepancy of opponents was found (r = 0.65, P < 0.05). CONCLUSION:
      collegiate wrestlers, excluding heavyweights, gained significant amounts of
      weight (3.7 kg average) during the 20-h period prior to tournament competition.
      The magnitude of weight gain was positively correlated to the degree of weight
      discrepancy (size advantage) over the opponent; however, because weight gain of
      some magnitude after the weigh-in was common in most participants, the average
      discrepancy between opponents was only about 1.5 kg.

PMID- 7808255
TI  - Correlation between choline level and Gd-DTPA enhancement in patients with brain
      metastases of mammary carcinoma.
AB  - Single voxel 1H double spin-echo MR spectroscopy was used to examine 15 cases of
      brain metastasis of mammary carcinoma (18 lesions) in relation to Gd-DTPA
      enhanced MR imaging. For lesions larger than 50% of MRS voxel size, there was
      significant correlation between Gd-DTPA-enhanced MRI signal and MRS-detected
      signal of choline (Cho) containing compounds (r = 0.86, P < 0.01; n = 8). The
      observed loss of correlation when including the smaller lesions was overcome by
      correcting for partial volume effects (r = 0.69, P < 0.002; n = 18). Metastasis
      spectra showed increased Cho compared with control spectra, except for those
      lesions showing detectable lactate (Lact) signal. The detection of Lact in four
      of the larger lesions coincided with comparatively low levels of creatine (Cr)
      and Cho and heterogeneous Gd-DTPA enhancement (Cr) and Cho and heterogeneous Gd
      DTPA enhancement (ring-enhancement). It was concluded that in brain metastases of
      mammary carcinoma Lact represents a product of ischemia preceding/during tissue
      decay resulting in central necrosis, rather than tumor specific metabolism
      resulting in increased glycolysis.

PMID- 7808256
TI  - 31P NMR and triple quantum filtered 23Na NMR studies of the effects of inhibition
      of Na+/H+ exchange on intracellular sodium and pH in working and ischemic hearts.
AB  - The triple quantum filtered 23Na NMR method is applied here to measure the
      effects of EIPA, a specific inhibitor of the Na+/H+ antiporter, on relative
      intracellular sodium concentrations in isolated working hearts at baseline,
      during ischemia, and at subsequent reperfusion. In analogy to the
      spectrophotometric isosbestic point, an approach is developed that defines a
      value of tau at which the effect of the relaxation times on the TQF signal
      intensities is minimized, and the signals are proportional to the sodium
      concentration for both ischemic and working hearts. EIPA at 1.5 microM
      significantly inhibited (P < 0.01) the influx of intracellular Na+ during 20 min
      of ischemia at 36.2 degrees C in this rat heart model. In parallel 31P NMR
      studies, EIPA had no effect on either the development of acidosis during ischemia
      or on the recovery of pHi during reperfusion despite its profound effect on
      intracellular Na+ influx. Thus, under our conditions the Na+/H+ antiporter did
      not play a critical role in the maintenance of intracellular pH. EIPA treatment
      resulted in improved recovery (P < 0.005) of mechanical function after 20 min of
      ischemia. [ATP] was higher in treated hearts during ischemia and reperfusion.

PMID- 7808257
TI  - Evaluation of cerebral gray and white matter metabolite differences by
      spectroscopic imaging at 4.1T.
AB  - Using a 4.1T whole body system, we have acquired 1H spectroscopic imaging (SI)
      data of N-acetyl (NA) compounds, creatine (CR), and choline (CH) with nominal
      voxel sizes of 0.5 cc (1.15 cc after filtering). We have used the SI data to
      estimate differences in cerebral metabolites of human gray and white matter. To
      evaluate the origin of an increased CR/NA and CH/NA ratios in gray matter
      relative to white matter, we measured the T1 and T2 of CR, NA, and CH in gray and
      white matter using moderate resolution SI imaging. In white matter the T2s of NA,
      CR, and CH were 233 +/- 27, 141 +/- 18, and 167 +/- 20 ms, respectively, and 227
      +/- 27, 140 +/- 16, and 189 +/- 25 ms in gray matter. The T1 values for NA, CR,
      and CH were 1267 +/- 141, 1487 +/- 146, and 1111 +/- 136 ms in gray matter and
      1260 +/- 154, 1429 +/- 233, and 1074 +/- 146 ms in white matter. After correcting
      for T1 and T2 losses, creatine content was significantly lower in white matter
      than gray (P < 0.01, t-test), with a white/gray content ratio of 0.8, in
      agreement with biopsy and in vivo measurements at 1.5 and 2.0T.

PMID- 7808258
TI  - Localized in vivo 31P NMR spectroscopy of skin flap metabolism.
AB  - We have used a rectangular surface coil and chemical shift imaging to conduct in
      vivo localized 31P NMR metabolic studies in a rat dorsal skin flap model. This
      approach permits regional comparisons without manipulation of either coil
      position or subject within the magnet bore. Both the PCr:Pi ratio (reflecting
      ischemia insult) and the PCr:ATP ratio (reflecting phosphagen reserves) decreased
      as functions of time and distance from the vascular pedicle. The maximum change
      was nearly 6-fold for the PCr:Pi ratio, and 3-fold for the PCr:ATP ratio. Signal
      contamination from subjacent muscle is constant and does not interfere with the
      metabolic evaluations of skin flaps. This technique may facilitate a better
      understanding of cutaneous metabolic derangements, such as burns and skin flaps
      used in reconstructive surgery, as well as studies of pharmacologic regimens
      developed for their treatment. It also holds potential for application in the
      study of congenital and neoplastic metabolic disorders of skin.

PMID- 7808259
TI  - Water diffusion in the giant axon of the squid: implications for diffusion
      weighted MRI of the nervous system.
AB  - To clarify the result that marked diffusional anisotropy had been found in
      nomyelinated nerve, and in completion of an evaluation of the role of all
      longitudinal axonal structures, we report NMR measurements of water diffusion in
      the giant axon of the squid, where diffusional anisotropy is determined by the
      neurofilamentary structure. The diffusion coefficients of water parallel and
      perpendicular to the long axis of the squid giant axon at 20 degrees C are (1.61
      +/- 0.06) x 10(-5) cm2 s-1 and (1.33 +/- 0.09) x 10(-5) cm2 s-1, respectively,
      which yield an anisotropic diffusion ratio of 1.2 +/- 0.1. Water diffusion in the
      squid giant axon is therefore quite rapid and nearly isotropic, thus eliminating
      the possibility of a significant role for the longitudinally oriented
      neurofilaments in producing diffusional anisotropy within the axoplasm. In
      conjunction with our work on garfish nerves therefore, only membranes, either as
      numerous axonal membranes or as myelin (if present), remain to fulfill the role
      of the primary determinant of anisotropic water diffusion in nerve and in white
      matter.

PMID- 7808260
TI  - Anisotropy of NMR properties of tissues.
AB  - Orientational anisotropy of T2 and T1 relaxation times, diffusion, and
      magnetization transfer has been investigated for six different tissues: tendon,
      cartilage, kidney, muscle, white matter, and optic nerve. Relaxation anisotropy
      was observed for tendon and cartilage, and diffusional anisotropy was measured in
      kidney, muscle, white matter, and optic nerve. All other NMR measurements of
      these tissues showed no orientational dependence. This pattern of NMR
      anisotropies can be interpreted from the underlying geometrical structures of the
      tissues.

PMID- 7808261
TI  - Estimation of total coronary artery flow using measurements of flow in the
      ascending aorta.
AB  - This paper describes a technique for estimation of total (right+left) coronary
      artery flow using MRI flow measurements in the ascending aorta. The technique is
      based on the principle that the flow in a vessel branch is equal to the
      difference of the net flow measured above and below the branch ostia. Aortic net
      flow is measured at four or more axial oblique slices from below the aortic valve
      to above the highest location of the coronary vessel ostia in late diastole. A
      flow model properly interprets the flow measurements in slices that contain the
      coronary ostia. Results in five normal subjects show that total coronary artery
      flow can be measured with a standard error of about 90 cc/min, 30% of total
      coronary artery flow. Potential clinical uses include noninvasive measurement of
      coronary flow reserve. Pulse sequence improvements are necessary to reduce
      examination time and improve accuracy and precision.

PMID- 7808262
TI  - The effect of high performance gradients on fast gradient echo imaging.
AB  - The effect of gradient system performance on segmented k-space gradient echo
      imaging is presented. Three cases were investigated. First, an ideal system that
      has infinite slew rates and unlimited maximum gradient strengths was considered.
      Second, a "high speed" imaging system (2.3 (G/cm), 23 (G/cm)/ms) was considered.
      These two cases were compared with a "conventional" imaging system (1(G/cm), 1.67
      (G/cm)/ms). It was found that substantial increases in SNR can be achieved
      (approximately 45%) by using high speed versus a conventional gradient system,
      for a TR of 6 ms. For trapezoidal gradient waveforms, there exists an optimum
      maximum gradient strength for a given slew rate, and any increase in gradient
      strength above this optimum will not be utilized by an optimized sequence. These
      studies have shown that increasing TR without decreasing the bandwidth is not a
      good way to increase SNR for constant scan time.

PMID- 7808263
TI  - Dynamic contrast-enhanced MR imaging of the upper abdomen: enhancement properties
      of gadobutrol, gadolinium-DTPA-polylysine, and gadolinium-DTPA-cascade-polymer.
AB  - The enhancement properties of gadobutrol (40 and 80 mumol/kg body weight, 550
      daltons), gadolinium-DTPA-polylysine (20 mumol/kg body weight, 53,000 daltons)
      and gadolinium-DTPA-cascade-polymer (20 mumol/kg body weight, < 30,000 Daltons)
      were investigated in abdominal MR imaging using a pig model (n = 24). Signal
      intensities before and after contrast media application were assessed using a
      fast single slice FLASH sequence. Measurements were made every 4 s within the
      first 116 s, every minute between 4 and 10 min and after 15, 20, 30, 40, 50, 60,
      90, and 120 min after contrast media injection. Injection of gadobutrol resulted
      in typical signal intensity curves characterizing it as an extracellular agent
      similar to gadopentetate dimeglumine. Significant enhancement was found in all
      tissues except the trunk muscles when the lower dose was administered. Gadolinium
      DTPA-polylysine injection resulted also in significant enhancement of the liver,
      the pancreas, and the renal cortex, but not of the trunk muscle, reflecting its
      blood pool properties known also from other macromolecular contrast agents. The
      signal intensity curves obtained after gadolinium-DTPA-cascade-polymer injection
      were similar to those obtained after polylysine injection, stressing the blood
      pool character of this new type of blood pool agent.

PMID- 7808264
TI  - Radial turbo spin echo imaging.
AB  - Fast MR imaging methods should provide a familiar contrast behavior at a reduced
      scan time. The multi-spin echo approach (TSE) is one of the most promising
      techniques satisfying this condition. Although the data acquisition time is
      significantly reduced, image quality may still suffer from artifacts due to
      patient motion and flow. The radial turbo spin echo (rTSE) approach combines TSE
      methods and projection reconstruction (PR) techniques. In PR images, artifacts
      induced by patient motion or flow are known to have a different appearance with
      lower level of intensity. The contrast and artifact behavior of the rTSE approach
      has been investigated. The new technique has been applied to abdominal imaging
      with acquisition times shorter than 30 s and to heart imaging in combination with
      cardiac triggering.

PMID- 7808265
TI  - Real-time motion detection in spiral MRI using navigators.
AB  - A technique has been developed whereby motion can be detected in real time during
      the acquisition of data. This enables the implementation of an algorithm to
      accept or reject and reacquire data during a scan. Frames of data with motion are
      rejected and reacquired on the fly so that by the end of the scan, a complete
      motion-free data set has been acquired. The algorithm has been implemented on
      several different types of sequences. Preliminary in vivo studies indicate that
      motion artifacts are dramatically reduced.

PMID- 7808266
TI  - Quantitative analysis of multi-slice Gd-DTPA enhanced dynamic MR images using an
      automated simplex minimization procedure.
AB  - Quantitative analysis of Gd-DTPA enhanced dynamic MR images has potential for
      discriminating lesions, especially because the introduction of clinical fast
      imaging techniques has enabled good sampling of the relatively rapid Gd-DTPA wash
      in curves. Analysis of such data requires curve fitting to a nonlinear model,
      which to date has been performed using a nonlinear least squares (NLLS) fitting
      procedure. However, this method often fails to converge to the appropriate minima
      without good initial parameter estimates when multi-exponential models are
      involved, making automated analysis of complete multislice or volume data sets
      problematic. In this report we demonstrate the robust performance of a simplex
      minimization procedure compared with NLLS, by the method of Marquardt, using a
      Monte Carlo simulation. Further, we illustrate the applicability of such a
      technique to the analysis of dynamic contrast enhanced images on a pixel-by-pixel
      basis. As a preliminary example, the technique is applied to a breast lesion but
      is expected to be suitable for examination of many lesion types.

PMID- 7808267
TI  - A new T2 preparation technique for ultrafast gradient-echo sequence.
AB  - The T2 contrast in images obtained with driven equilibrium (90degreesx
      180degreesx-90degreesx) prepared ultrafast gradient-echo sequence is compromised
      by the longitudinal magnetization build-up after the second 90degreesx pulse,
      which does not carry T2 information. This paper describes a new T2 contrast
      preparation technique for ultrafast gradient-echo sequence that suppresses the
      signal arising from the build-up. By dephasing in the preparation and rephasing
      in the acquisition of the gradient echoes, the new technique eliminates signals
      that are not dictated by the T2 contrast in a driven-equilibrium approach.
      Consequently, it generates an image that is essentially T2-weighted. Phantom and
      in vivo experiments were conducted to validate the technique and to demonstrate
      its clinical utility. These studies indicate that the technique works properly
      and can be used for in vivo studies.

PMID- 7808268
TI  - Reduced power selective excitation radio frequency pulses.
AB  - A pulse synthesis algorithm is described that allows for the synthesis of
      selective radio frequency pulses requiring less peak power. The pulses thus
      synthesized have the same duration, total energy, and frequency response as those
      synthesized by the standard algorithm. Their phase function is, however,
      different. The power reduction is typically on the order of 60-70%. This
      modification will increase the utility of optimized selective pulses.

PMID- 7808269
TI  - High speed bolus tagging: time resolved velocity quantification of pulsatile flow
      in a single breath hold.
AB  - We have implemented a high speed method for cardiac-triggered blood velocity
      quantification within a single breath hold on a conventional MR system. The
      method, based on bolus tagging, was tested using a pulsatile flow phantom and
      evaluated in vivo. The image acquisition time was reduced by a factor of N by
      acquiring N phase encode lines per bolus tag application. The clarity of the flow
      tag was found to vary with how k-space was covered during data collection. The
      technique was optimized and multiple bolus tag images were obtained throughout
      the cardiac cycle within a single breathold.

PMID- 7808270
TI  - Echo-volume imaging.
AB  - Two single-shot volume imaging techniques are described. The first, single-echo
      echo-volume imaging, is essentially the echo-volume imaging (EVI) sequence
      suggested by Mansfield (J. Phys. C. 10, L55 (1977)). The second is a multi-spin
      echo approach in which one plane of k-space is collected during each spin echo.
      In both techniques, phase encoding gradients are applied in the z direction, and
      three-dimensional k-space is filled by a raster pattern in Cartesian coordinates.
      Spatial saturation is used to avoid aliasing in the y direction, and a selctive
      pulse is applied to excite the desired slab of tissue and eliminate aliasing in
      z. The average echo-times, measured from the center of the 90 degrees pulse to
      the center of the acquisition k-space (kx = ky = kz = 0), were 45 and 104 ms for
      single echo and multi-echo methods, respectively. Images of the human brain using
      both sequences are shown.

PMID- 7808271
TI  - Detection of apparent restricted diffusion in healthy rat brain at short
      diffusion times.
AB  - The application of bipolar diffusion sensitizing gradient pulses to significantly
      reduce the diffusion time is described. This approach is combined with the rapid
      U-FLARE imaging sequence. Three diffusion-sensitized types of experiments are
      compared and their suitability for detecting restricted diffusion is discussed.
      Experiments using a modification of the diffusion weighting by varying the
      diffusion time between 1.6 and 6.0 ms obtained nonmonoexponential signal
      attenuation curves from both healthy brains and postmortem. This behavior is
      indicative of restricted diffusion, but as it is detectable only at short
      diffusion times, in contrast to a restriction due to impermeable barriers, we
      have termed this "apparent restriction."

PMID- 7808272
TI  - Three-dimensional time-of-flight MR angiography with variable TE (VARIETE) for
      fat signal reduction.
AB  - Uniform fat saturation over a large region of interest remains a problem in time
      of-flight (TOF) magnetic resonance angiography applications. We demonstrate that
      a variable echo time with an opposed phase value at low spatial slice select
      frequencies can effectively reduce most of the fat signal in an otherwise
      standard three-dimensional TOF acquisition. We evaluated this method at 1.5 T
      using a short TE = 5.3 ms and a long TE = 6.75 ms for different values of the
      slice encoding gradient (i.e., different kz values). Shorter echo time (TE = 5.3
      msec) was used at higher spatial slice select frequencies, but all echoes have
      the same gradient structures. By keeping the number of slice encoding steps with
      longer echoes to a minimum, field inhomogeneity effects on flow compensation
      remained small. A magnetization transfer saturation pulse was used to suppress
      signal of brain parenchyma. Overall, highly uniform and selective fat signal
      reduction was obtained while maintaining superior flow compensation in all
      volunteer studies.

PMID- 7808273
TI  - Place recognition and way finding by children and adults.
AB  - Children and adults were escorted on their first walk across our university
      campus and were periodically led off the original route during the return trip.
      During the return, we stopped prior to intersections on and off the original
      route to obtain estimates of place recognition accuracy and confidence. The
      subjects were then asked to point to the path that led back to the start and were
      corrected if wrong. Accuracy of place recognition was intermediate in a way
      finding task requiring reversal of an incidentally learned novel route. However,
      accuracy increased as subjects were farther from the original route, indicating
      that the presence of novel landmarks boosted the discrimination of old and new
      places. Eight-year-old children were less accurate than 12-year-old children and
      25-year-old adults, who did not differ in accuracy. There was a similar age
      difference in the ability to point to the direction to return when subjects
      correctly recognized that they were off route. The results are used to develop a
      model of way finding by place recognition.

PMID- 7808274
TI  - Substituting new details for old? Effects of delaying postevent information on
      infant memory.
AB  - How that which we remember is selectively distorted by new information was
      studied in 3-month-old infants who learned to move a particular crib mobile by
      operant foot kicking. Infants who were passively exposed to a novel mobile 1, 2,
      or 3 days later subsequently treated the novel mobile as if they had actually
      been trained with it. Also, after the longest exposure delay, they no longer
      recognized the original mobile. Likewise, when the novel mobile was exposed after
      the longest delay, it could prime the forgotten training memory in a reactivation
      paradigm, but the original mobile no longer could. These data reveal that what we
      remember about an event is selectively distorted by what we encounter later.
      Moreover, the later in the retention interval we encounter new postevent
      information, the greater is its impact on retention.

PMID- 7808276
TI  - Controlled attention sharing influences time estimation.
AB  - A seminal attentional model of time estimation predicts that subjective duration
      will be positively correlated to the amount of attention given to temporal
      processing. This prediction holds under prospective conditions, in which one is
      forewarned that judgments of time will be asked, in contrast to retrospective
      conditions, in which such judgments are required after the relevant period
      without any prior warning. In three experiments, an attention-sharing method was
      used. Subjects were asked to control the amount of attention that they devoted to
      one or the other component of a dual-task paradigm. The first experiment involved
      word categorization and reproduction of duration. The following experiments,
      based on signal detection theory, required discrimination of both the duration
      and the intensity of a single stimulus, in the visual (Experiment 2) or the
      auditory (Experiment 3) modality. The results indicate that when the attention is
      directly controlled by the subject, the subjective duration shortens as the
      amount of attention devoted to the temporal task diminishes. The implications of
      these results for the possible existence of an internal timer are considered.

PMID- 7808275
TI  - Priming of pop-out: I. Role of features.
AB  - We examined a visual search task, in which observers responded to the high-acuity
      aspect of a pop-out target (shape of an odd-colored diamond or vernier offset of
      an odd spatial-frequency patch). Repetition of the attention-driving feature
      (color or spatial frequency) in this task primes the pop-out; repetition of the
      high-acuity aspect (shape, vernier offset) does not. Priming of pop-out is due to
      a decaying memory trace of the attention-focusing feature laid down with each
      trial. The trace exerts a diminishing effect over the following five to eight
      trials (approximately 30 sec), and its influence over this time is cumulative.
      Observers cannot wilfully overcome the priming, which suggests that it is passive
      and autonomous. Both target facilitation and distractor inhibition are evident;
      the former has a greater effect. The phenomenon shows complete binocular
      transfer.

PMID- 7808277
TI  - Implicit and explicit memory for compound words.
AB  - Subjects studied visually presented compound words (e.g., TOOTHPASTE, HEARTACHE)
      and then received a recognition, perceptual identification, or word-fragment
      completion test that contained old, recombined (e.g., TOOTHACHE), and partially
      and completely new words. False recognitions increased with the increasing number
      of previously studied components; however, priming in perceptual identification
      occurred only for old words. Priming in word-fragment completion occurred for old
      and recombined words. Reducing the time available to solve word fragments, from
      20 sec to 5 sec, did not affect the pattern of results; it is therefore unlikely
      that priming for recombined words resulted from the use of a recollection-based
      strategy. Memory tasks that involve a conceptual component access memories that
      are constructed from parts; memory tasks that are primarily perceptual do not
      access such memories.

PMID- 7808278
TI  - Effects of word frequency and age of acquisition on short-term memory span.
AB  - The experiments reported examine the effects of two highly related variables,
      word frequency and age of acquisition, on short-term memory span. Short-term
      memory span and speech rate were measured for sets of words which independently
      manipulated frequency and age of acquisition. It was found that frequency had a
      considerable effect on short-term memory span, which was not mediated by speech
      rate differences--although frequency did affect speech rate in one experiment.
      For age of acquisition, this situation was reversed; there was a small but
      significant effect of age of acquisition on speech rate, but no effect on memory
      span. This occurred despite results confirming that the stimuli used in the
      experiments produce an effect of age of acquisition on word naming. The results
      are discussed in terms of a two-component view of performance on short-term
      memory tasks.

PMID- 7808279
TI  - Further constraints on the bizarreness effect: elaboration at encoding.
AB  - In this study, we attempted to determine why the mnemonic benefit of bizarreness
      is not found with the use of complex sentences (i.e., those containing additional
      modifiers of nouns) as stimuli. Several explanations were investigated, including
      the idea that complexity reduces the imageability of the sentence and the idea
      that complexity itself is mnemonically beneficial. The results of four
      experiments favored the latter explanation. We suggest that the cues associated
      with the complexity of the sentence provide more effective or salient retrieval
      cues than do those associated with sentence bizarreness. Consequently, the
      mnemonic benefit of bizarreness appears to occur only with relatively
      impoverished encoding contexts (e.g., simple, unelaborated sentences).

PMID- 7808280
TI  - Reflections of the mirror effect for item and associative recognition.
AB  - In five experiments, participants studied pairs of words and yes/no recognition
      memory for both item and associative information was tested. Two stimulus
      manipulations, nouns versus nonnouns and high versus low word concreteness,
      produced the mirror effect for both item and associative recognition. The mirror
      effect was reflected in both measures of accuracy and response latency. A word
      frequency manipulation, however, produced the mirror effect only for item
      recognition. Two additional experiments showed that the mirror effect could also
      be obtained between nouns and nonnouns and between high and low concrete words
      for associative recognition in a forced-choice recognition procedure. The results
      extend the generality of the mirror effect to measures of response latency and to
      associative recognition and also suggest that similar retrieval and decision
      processes underlie recognition of item and associative information.

PMID- 7808281
TI  - The effect of retrieval enactment on recall of subject-performed tasks and verbal
      tasks.
AB  - The effect of retrieval enactment on memory for nouns (objects) or verbal phrases
      describing simple actions (e.g., "lift the box") was addressed in two
      experiments. In Experiment 1, the type of object involved in the actions was
      manipulated, with three different types of object being used (body parts,
      laboratory-related objects, and external objects). In Experiment 2, the
      integration between the verb-noun pairs was manipulated (well-integrated vs.
      poorly integrated). Results from both experiments showed that whereas encoding
      enactment (motor encoding and verbal test) substantially improved the memory
      performance compared with a verbal condition (verbal encoding and verbal test),
      retrieval enactment (verbal encoding and motor test) had no major impact on the
      number of recalled nouns or phrases. Moreover, there was no additional effect of
      dual enactment (motor encoding and motor test). The overall pattern of the
      results suggests that there is a fundamental difference between motor processing
      at encoding and motor processing at retrieval, and the lack of encoding
      specificity advantage for the motor modality contradicts the view that encoding
      enactment of verbal commands results in storage of motor representations.

PMID- 7808282
TI  - Semantic memory and the granularity of semantic relations: evidence from speed
      accuracy decomposition.
AB  - In the present study we examined whether semantic relations are atomistic unitary
      associations, or are complex concepts consisting of a number of relational
      elements. The complexity of the ownership relation was assessed by combining a
      relation verification task ("Many people own [cars/comets]") with the speed
      accuracy decomposition procedure (Meyer, Irwin, Osman, & Kounios, 1988). The
      latter permits one to determine whether subjects achieve their final state of
      response accuracy in a single, discrete all-or-none transition, or whether the
      relevant processes yield partial information representing intermediate states of
      knowledge. The rationale was that the retrieval of a unitary relational link from
      a classical associative network should be an all-or-none affair. In contrast, a
      set of relational elements need not be processed as a unitary bundle, thereby
      allowing partial response-information states. In two experiments, we found
      evidence of such partial information (i.e., sensitivity in units of d'), lending
      support to the notion that relations are complex. Furthermore, the results
      suggest that the accumulation of guessing sensitivity was linear over time,
      weighing against alternate theoretical interpretations.

PMID- 7808283
TI  - Interpretational factors in conditional reasoning.
AB  - Two experiments examined the role of necessity and sufficiency relationships in
      conditional reasoning. The results indicated that perceived necessity and
      sufficiency predicted variability in reasoning performance for four pragmatic
      relations (permission, obligation, causation, and definition), for both
      determinant and indeterminant syntactic forms, and for both a conditional
      arguments and a truth table evaluation task, as well as when the temporal
      relationship between the antecedent and consequent events was reversed. These
      data support the general utility of perceived necessity and sufficiency in the
      interpretation and evaluation of conditional relationships. However, the effects
      of necessity and sufficiency were smaller for reversed than for forward
      statements, which suggests that necessity/sufficiency-based interpretations may
      be more useful for evaluating some types of conditional relations than others. In
      addition, people were more likely to accept valid rather than invalid arguments,
      regardless of necessity/sufficiency relations, a finding that suggests that
      abstract, content-free representations may play a functional role in conditional
      reasoning.

PMID- 7808284
TI  - Purification and properties of yeast redoxyendonuclease.

PMID- 7808285
TI  - Shuttle vector between prokaryotes and eukaryotes for assaying singlet oxygen
      induced DNA damage and mutagenicity.

PMID- 7808286
TI  - Oxidative DNA damage: endonuclease fingerprinting.

PMID- 7808287
TI  - Effect of reactive oxygen intermediates and antioxidants on proliferation and
      function of T lymphocytes.

PMID- 7808288
TI  - Assessing oxygen radicals as mediators in activation of inducible eukaryotic
      transcription factor NF-kappa B.

PMID- 7808289
TI  - Assays of oxidative DNA damage biomarkers 8-oxo-2'-deoxyguanosine and 8
      oxoguanine in nuclear DNA and biological fluids by high-performance liquid
      chromatography with electrochemical detection.
AB  - High-performance liquid chromatography with electrochemical detection is a highly
      sensitive and selective method for detecting oxo8dG and oxo8Gua, biomarkers of
      oxidative DNA damage. When employed together with the DNA isolation and
      monoclonal antibody-based immunoaffinity purification methods described, oxo8dG
      and oxo8Gua in DNA and urine can be readily detected and quantitated, offering a
      powerful approach for assessing oxidative DNA damage in vivo. Application of the
      technique to the detection of oxo8dG from DNA permits quantitation of the steady
      state levels of this oxidatively modified deoxynucleoside and overcomes the
      detection problems associated with the extremely low levels present in DNA. In
      addition, the selectivity gained by this detection method eliminates the problem
      of separating the signal for oxo8dG from those of normal deoxynucleosides. The
      quantitation of oxo8dG and oxo8Gua in biological fluids is noninvasive and
      complements the measurement of oxo8dG in DNA by estimating the rate of oxidative
      DNA damage occurring within the body or in a population of cells. This analytical
      approach may allow one to estimate oxidative DNA damage in an animal or
      individual exposed to prooxidant conditions associated with lifestyle, genetic
      predisposition, degenerative diseases, or environmental toxins. Furthermore,
      these assays may allow one to assess the potentially beneficial effects of
      intervention strategies that protect DNA from such damage.

PMID- 7808290
TI  - Analysis of c-Fos and c-Jun redox-dependent DNA binding activity.

PMID- 7808291
TI  - Assays for regulation of gap junctional communication and connexin expression by
      carotenoids.

PMID- 7808292
TI  - Evaluation of biomolecular damage by ozone.

PMID- 7808293
TI  - Ozone exposure of cultured cells and tissues.

PMID- 7808294
TI  - Measurement of antioxidants in human blood plasma.
AB  - The concentration of antioxidants in human blood plasma is important in
      investigating and understanding the relationship between diet, oxidant stress,
      and human disease. The HPLC-EC technique combines selectivity with high
      sensitivity for measuring both water- and lipid-soluble antioxidants. The
      excellent sensitivity of the methods described here allows one to measure a panel
      of antioxidants in a small volume of plasma.

PMID- 7808295
TI  - Total antioxidant status in plasma and body fluids.

PMID- 7808296
TI  - Analysis of vitamin E homologs in plasma and tissue: high-performance liquid
      chromatography.

PMID- 7808297
TI  - Chemical determination of oxidative DNA damage by gas chromatography-mass
      spectrometry.

PMID- 7808298
TI  - Separation of the eight stereoisomers of all-rac-alpha-tocopherol from tissues
      and plasma: chiral phase high-performance liquid chromatography and capillary gas
      chromatography.

PMID- 7808299
TI  - Tocopherone and expoxytocopherone products of vitamin E oxidation.

PMID- 7808300
TI  - Light-induced generation of vitamin E radicals: assessing vitamin E regeneration.

PMID- 7808302
TI  - Determination of tocopherols and tocopherolquinone in human red blood cell and
      platelet samples.

PMID- 7808301
TI  - Antioxidative activity of tocotrienol in heterogeneous system: indication of
      restriction within membrane by fluorescence measurement.

PMID- 7808303
TI  - Detection and characterization of eukaryotic enzymes that recognize oxidative DNA
      damage.

PMID- 7808304
TI  - Vitamin C, dehydroascorbate, and uric acid in tissues and serum: high-performance
      liquid chromatography.

PMID- 7808305
TI  - In vivo determination of superoxide and vitamin C radicals using cytochrome c and
      superoxide dismutase derivatives.

PMID- 7808306
TI  - Assay of ubiquinones and ubiquinols as antioxidants.

PMID- 7808307
TI  - Antioxidant properties of alpha-tocopherol and alpha-tocotrienol.

PMID- 7808308
TI  - Determination of oxidized glutathione in blood: high-performance liquid
      chromatography.

PMID- 7808309
TI  - Antioxidant activity of alpha-tocopherol, beta-carotene, and ubiquinol in
      membranes: cis-parinaric acid-incorporated liposomes.

PMID- 7808310
TI  - Singlet oxygen quenching by carotenoids.

PMID- 7808311
TI  - Separation of geometrical isomers of beta-carotene and lycopene.

PMID- 7808312
TI  - Lipoperoxyl radical-scavenging activity of vitamin A and analogs in homogeneous
      solution.

PMID- 7808313
TI  - Naturally occurring flavonoids: structure, chemistry, and high-performance liquid
      chromatography methods for separation and characterization.

PMID- 7808314
TI  - Flavonoid antioxidants: rate constants for reactions with oxygen radicals.

PMID- 7808315
TI  - Assay of condensed tannins or flavonoid oligomers and related flavonoids in
      plants.

PMID- 7808316
TI  - Role of flavonoids and iron chelation in antioxidant action.

PMID- 7808317
TI  - Actions of flavonoids and coumarins on lipoxygenase and cyclooxygenase.

PMID- 7808318
TI  - Localization of strand breaks in plasmid DNA treated with reactive oxygen
      species.

PMID- 7808319
TI  - Determination of structure-antioxidant activity relationships of dihydrolipoic
      acid.

PMID- 7808321
TI  - Ebselen: a glutathione peroxidase mimic.

PMID- 7808322
TI  - N-acetylcysteine.

PMID- 7808320
TI  - Antioxidant action of Ginkgo biloba extract EGb 761.

PMID- 7808323
TI  - Preparation and use of glutathione monoesters.

PMID- 7808324
TI  - Preparation and properties of glutathione diethyl ester and related derivatives.

PMID- 7808325
TI  - Antioxidant activity and serum levels of probucol and probucal metabolites.

PMID- 7808326
TI  - Detecting DNA damage caused by iron and hydrogen peroxide.

PMID- 7808327
TI  - Alpha-phenyl N-tert-butylnitrone as antioxidant for low density lipoproteins.

PMID- 7808328
TI  - Brain antioxidant activity of spin traps in Mongolian gerbils.

PMID- 7808330
TI  - Penicillamine as antioxidant.

PMID- 7808329
TI  - Antioxidant activity of nitecapone and its analog OR-1246: effect of structural
      modification on antioxidant action.

PMID- 7808331
TI  - Antioxidant action of lazaroids.

PMID- 7808332
TI  - Antioxidant properties of aminosalicylates.

PMID- 7808333
TI  - Antioxidant action of stobadine.

PMID- 7808334
TI  - Nitroxides as antioxidants.

PMID- 7808335
TI  - Photochemical synthesis of 8-hydroxyguanine nucleosides.

PMID- 7808337
TI  - Reactivity of plasmalogens to singlet oxygen and radicals.

PMID- 7808336
TI  - Tamoxifen and estrogens as membrane antioxidants: comparison with cholesterol.

PMID- 7808338
TI  - Antioxidant activity of calcium channel blocking drugs.

PMID- 7808339
TI  - Interactions of phenoxyl radical of antitumor drug, etoposide, with reductants in
      solution and in cell and nuclear homogenates: electron spin resonance and high
      performance liquid chromatography.

PMID- 7808341
TI  - Singlet oxygen DNA damage: chromatographic and mass spectrometric analysis of
      damage products.

PMID- 7808340
TI  - Copper--DNA adducts.

PMID- 7808342
TI  - Alkaline elution versus fluorescence analysis of DNA unwinding.

PMID- 7808343
TI  - [Relations between mental health and work. Review of the literature].
AB  - Interest in occupational mental illness has increased as a result also of the
      technological changes at the workplace. A total of 22 epidemiological studies on
      this topic were reviewed on the following basis: subject of the study,
      epidemiological design, type of psychometric scale, results. The authors discuss
      the methods and constraints of these studies, especially the lack of knowledge on
      occupational exposure and its relationship to mental health. The need for further
      studies in order to improve prevention of mental illness at the workplace is
      stressed.

PMID- 7808344
TI  - [Normal values of carboxyhemoglobinemia and methemoglobinemia in a sample of
      conscripts].
AB  - Carboxyhemoglobin (COHb) and methemoglobin (MetHb) values in blood were measured
      in a population of 296 asymptomatic conscripts who were not under medical
      treatment and had no occupational exposure. The mean COHb value was 3.25 (S.D. =
      1.45%) in smokers and 1.34 (S.D. = 0.8) in non-smokers, with a wide variability
      in both subgroups, particularly among smokers. The COHb levels in moderate
      smokers were lower than in heavy smokers, but smoking just before the blood test
      greatly increased the COHb levels. Non-smoking country dwellers had lower COHb
      levels than non-smoking city dwellers, but the COHb levels of smokers were
      independent of residence and were only smoking-related. The sample MetHb level
      was 0.81 (S.D. = 0.37) and was influenced by country living and smoking. Levels
      were lowest in non-smoking country dwellers (0.66, S.D. = 0.38%) and increased
      with moderate smoking (0.71, S.D. = 0.40%). Heavy smoker levels were independent
      of residence. Smoking just before the blood test had no effect on the value.

PMID- 7808345
TI  - [Evaluation of initial results of treatment of lead poisoning with EDTA].
AB  - The results of EDTA therapy were studied in 37 workers of a battery factory
      consisting of males with varying degrees of occupational lead poisoning (low
      exposure: 10 subjects, blood lead levels (PbB) lower than 400 micrograms/l with
      slight alterations in heme biosynthesis; beyond limit of effect: 5 subjects, PbB
      > 400 micrograms/l; slight intoxication: 19 subjects, with marked alterations in
      heme synthesis and preclinical signs of intoxication; average degree of
      intoxication: 3 subjects with clinical signs of intoxication. Clinical symptoms
      and the following parameters were investigated: blood lead (PbB), delta
      aminolevulinic acid dehydratase in erythrocytes (ALA-D), zinc protoporphyrin (PP)
      in erythrocytes and delta-aminolevulinic acid (ALA) in 24-hour urine before and
      after EDTA chelating therapy. Simultaneous measurement of ALA-D and PP showed
      high diagnostic sensitivity in detecting lead poisoning in occupationally exposed
      subjects. In view of the high interindividual variability of the results, these
      indices did not, however, permit a useful differentiation to be made of the
      different degrees of intoxication at individual level, even though a good
      correlation was observed between PbB and porphyrin metabolism indices. From the
      alterations observed in ALA-D and PP values it was not possible to establish an
      association between degree of alteration and types of clinical symptoms in the
      different intoxication studies. At the end of EDTA treatment, a clinical
      improvement was observed in all cases studied but only in 5 cases was a reduction
      in PbB observed, to levels below 1.20 mol/l, which is accepted as a permissible
      limit for the general population; in 17 cases PbB remained at levels above the
      critical value for occupational lead poisoning (400 micrograms/l), although there
      was a decrease after treatment. The improvement observed in the indices of
      porphyrin metabolism at the end of treatment was only slight: significant
      variations were measured only for PbB. After treatment no association was
      observed between ALA-D and PP variations in erythrocytes and improvement in
      clinical symptoms; measurement of these indices therefore seems to be of little
      use in assessing the efficacy of the treatment. In spite of its limited
      diagnostic sensitivity during intoxication, measurement of ALA in urine could be
      useful to assess the efficacy of chelating therapy in subjects in whom the values
      are initially altered.

PMID- 7808346
TI  - [Decrease in the n-hexane risk in shoe manufacturing industry].
AB  - In recent years the composition of the glues used in the shoe manufacturing
      industry in the "Riviera del Brenta" area (northern Italy) has changed
      considerably, with a gradual reduction of n-hexane. This fact emerged from a
      survey of 337 gluing stations in 105 shoe factories where 104 different
      commercial products containing organic solvents were found. The determining
      element in this change was the substitution of technical hexane with other
      refinery products which have a low n-hexane content (< 5%). There was a possible
      health risk due to n-hexane exposure in about only 10% of the gluing stations and
      in about 8% of commercial products, where mixtures of technical hexane are used.
      Ethyl acetate, cyclo-hexane, hexane isomers, methyl ethyl ketone, heptane and
      acetone are among the solvents most frequently used. This change means that
      assessment of glue composition will be necessary before beginning a health
      monitoring programme of the exposed population.

PMID- 7808347
TI  - [Behavior of 8000 Hz audiometric threshold in chronic acoustic trauma].
AB  - The paper analyzes the 8 KHz threshold in subjects with noise-induced hearing
      loss. The study group consisted of 315 subjects occupationally exposed to noise
      and suffering from acoustic trauma, which was considered as a mean threshold of
      more than 25 dB at 2, 3 and 4 KHz. The mean shape of audiograms was characterized
      by a neurosensory deficit which was more elevated at 4 and 6 KHz whereas the
      threshold at 8 KHz was better. However, this pattern was found in 60% of the
      cases whereas in the remaining 40% the threshold at 8 KHz was worse. Subjects
      with the most impaired audiometric threshold at 8 KHz were mainly older, although
      cases were found in a low percentage of younger subjects. The results demonstrate
      that in individual cases it is impossible, on the basis of the shape of the
      audiogram, to establish whether a hearing loss is due to noise or age.

PMID- 7808348
TI  - [Allergic diseases caused by pesticides: 3 case reports].
AB  - Current pesticide exposure levels can induce a state of sensitization in exposed
      workers and only in exceptional situations cause severe intoxication. Three cases
      are reported--one suffering from urticaria/angio-edema, one from asthma and the
      other from oculo-rhinitis. Only one subject was atopical. The substances to which
      sensitization was found were Cynoxamil, Mancozeb, Thiophanate, Seccatutto for the
      first case, Paraquat for the second and Dodine for the third subject. The results
      suggest the need to extend allergological tests also to pesticides when workers,
      or subjects in any case exposed, show clinical signs with suspected immunological
      pathogenesis. Furthermore, in order to reduce the number of new cases of
      pesticide allergy, a more severe control also of subjects exposed to low doses is
      proposed.

PMID- 7808349
TI  - [Mortality rate and its statistical properties].
AB  - The rate is an epidemiologic measure which has a widespread use in describing the
      occurrence of diseases. In this paper, with a didactic approach, the definition
      of the mortality (morbidity) rate is introduced following two ways of reasoning:
      firstly, in the context of survival analysis, as an instantaneous conditional
      probability of failure (either disease or death) (instantaneous risk) and,
      secondly, as a traditional measure of rapidity of change in time. We then proceed
      to highlight the differences, in terms of definition, interpretation, and
      application, between the concepts of rate and risk. As a next step the
      statistical properties of the rate are explored and it is explained why the
      variability of the measure is simply associated with the numerator (events) and
      not with the denominator (person-times) of the rate. In this context the Poisson
      distribution is commonly considered the probability distribution which better
      describes the statistical variability of the observed events, and examples of
      such a distribution are presented. When the number of deaths is sufficiently
      elevated the Poisson distribution can be adequately approximated by the Gauss
      distribution, which is simpler and in common use in occupational medicine, and
      formulas are presented to compute mean and variance of the rate in this
      situation. When the number of deaths is small a suggestion is made of making a
      log transformation of the rate (or of the deaths) before using the Gauss
      distribution: formulas are proposed for this situation, too. As a practical
      application of the statistical properties presented and as a concluding example,
      a confidence interval for the rate is computed. Numerical and graphical
      comparisons of the results deriving from the use of different formulas are
      described.

PMID- 7808350
TI  - [Cassino and the 1st sentence in the world that acknowledges recent scientific
      discoveries: cancer due to depression caused by accident].

PMID- 7808351
TI  - [The risk of splenectomy].
AB  - BACKGROUND: The controversely discussed effect of splenic loss and disturbances
      of the general state of health are to be reported by means of several check
      sheets. There is a control group for comparison and statistic evaluation. The
      results will be considered in relation to laboratory serum parameters. PATIENTS
      AND METHOD: 111 patients splenectomized for various reasons could be examined 3
      to 17 years following surgery. We applied the depression check sheet by Beck, the
      Giessen complaint check sheet, and a specific splenectomy check sheet. The latter
      served to inquire an additional control group of statistic twins who underwent
      comparable upper abdominal surgery, but not splenectomy. Furthermore, 42
      laboratory serum parameters were determined in every splenectomized patient.
      RESULTS: Compared to random tests with the Federal Republic's population, the
      Giessen complaint check sheet detected a more frequently disturbed state of
      health in "spleenless". An evaluation of the specific splenectomy check sheet
      detected an increased trend for infections after splenectomy (p = 0.0000001)
      compared to those after upper abdominal surgery. There was no statistical proof
      for other typical symptoms such as incompatibility with alcohol or vegetative
      dystonia. There was no significant anomaly in the 42 parameters measured.
      CONCLUSION: Every other splenectomized patient complained about frequent
      infections and, consequently, disturbed state of health (physical weakness, early
      exhaustion). These complaints did not correlate to the measured laboratory serum
      parameters.

PMID- 7808352
TI  - [Changes in the blood picture after radioiodine therapy of thyroid cancer].
AB  - AIM: In this study the effect of radioiodine which was administered because of
      thyroid carcinoma on blood count and various other parameters was examined.
      PATIENTS AND METHODS: In 567 patients who had been treated because of a thyroid
      carcinoma between 1980 and 1990 with radioiodine, changes of hemoglobin, RBC,
      WBC, platelets, potassium, uric acid, gamma GT, GOT, GPT and AP were measured in
      correlation with the totally administered dose. RESULT: In low doses (< 18.5 GBq
      [500 mCi]), which are sufficient in most cases with clinical course without
      complications, relevant changes of blood count (hemoglobin: < or = 9.0/10.5 g/dl,
      RBC: < or = 3.1/3.5 10(12)/l (female/male), WBC: < or = 2.5 10(9)/l, platelets: <
      or = 0.5 10(11)/l) were observed in only 5 out of 469 cases. After moderate doses
      (> or = 18.5 GBq [500 mCi] and < 37 GBq [1000 mCi]) we found in only 1 out of 77
      cases relevant changes. After very high doses (> or = 37 GBq [1000 mCi]), which
      are used to treat metastases and/or recurrences, thrombopoesis is most sensitive
      to the radiation exposure of the bone marrow. Relevant decrease of RBC and WBC
      were observed in 2 out of 21 patients. Pancytopenia (hemoglobin: < or = 12.0/13.5
      g/dl, RBC: < or = 3.9/4.3 10(12)/l [female/male], WBC: < or = 3.5 10(9)/l,
      platelets: < or = 1.4 10(11)/l) occurred in 4 cases. CONCLUSION: In high-dose
      therapy with radioiodine frequent (monthly, but in any cases before each therapy)
      controls of blood count are necessary. In patients without metastases or
      recurrence no relevant changes can be expected in most cases.

PMID- 7808354
TI  - [The value of ultrasound in detection of collected gas in the portal vein or
      hepatic veins].

PMID- 7808353
TI  - [The status of the gonadotropin releasing hormone test in differential diagnosis
      of delayed puberty in adolescents over 14 years of age].
AB  - BACKGROUND: In patients with delayed puberty with a bone age less than 11 years
      in girls or 12 years in boys, the clinical and endocrinological examination
      allows the differentiation of patients with the various forms of
      hypergonadotropic hypogonadism, but not of patients with hypogonadotropic
      hypogonadism from more prevalent constitutional delay in puberty. Therefore,
      watchful waiting is generally recommended for differential diagnosis in patients
      with delayed puberty. On the other hand, the late onset of sexual hormone
      replacement in patients with hypogonadism will worsen their outcome. PATIENTS AND
      METHOD: Therefore, we decided to carry out a retrospective study in 105
      adolescents who were examined because of short stature or delayed puberty, who
      were aged 14 to 22 years at first visit and in whom the differential diagnosis of
      delayed puberty was documented after an at least one-year follow-up in order to
      find out which endocrinological parameters could have effectively predicted the
      final diagnosis already at the first visit. RESULTS: Patients with
      hypogonadotropic hypogonadism differed from patients with constitutional delay in
      puberty by lower responses of luteinizing hormone (LH) and follicle-stimulating
      hormone (FSH) levels to gonadotropin-releasing hormone stimulation (GnRH, 100
      micrograms iv) (p < 0.01) as well as by smaller testicular volume (p < 0.05) and
      by lower testosterone levels (p < 0.01). Stimulated LH < 10 mU/ml differentiated
      patients with hypogonadotropic hypogonadism from constitutional delay in puberty
      with a sensitivity of 82% and a specificity of 98%. CONCLUSION: In patients with
      delayed puberty aged 14 years and older bone age usually exceeds 11 years in
      girls or 12 years in boys. It thus is in the range, in which normal adult
      responses of LH to GnRH can be expected. In contrast to patients aged less than
      14 years, therefore, measuring GnRH-stimulated LH levels in these patients allows
      the rapid and effective differential diagnosis of delayed puberty.

PMID- 7808355
TI  - [Differential diagnosis of lumbosacral radicular symptoms].

PMID- 7808357
TI  - [Animal experiments used in clinical research].

PMID- 7808356
TI  - [Current therapeutic strategies in AIDS-associated Kaposi sarcoma. An overview
      including results of a personal study].

PMID- 7808358
TI  - [Rapidly progressing dilatative myocardial disease in a 37-year-old man.
      Myocarditis or dilatative cardiomyopathy?].

PMID- 7808360
TI  - [Who attends the 100th Meeting of the German Society of Internal Medicine.
      Evaluation of a questionnaire].

PMID- 7808359
TI  - [75-year-old woman with recurrent cerebral infarcts and secondary polyglobuly].

PMID- 7808362
TI  - [Caloric intake in parenteral nutrition of very low weight infants].
AB  - To evaluate the efficacy of a measure able to compare energy intake from
      parenteral and enteral nutrition we documented growth patterns in a group of VLBW
      infants treated with parenteral nutrition (PN). To analyze comparative energy
      intake from the two sources we expressed a percentage of both parenteral and
      enteral calories: the former (RCP%) related to an optimal value of 85 non protein
      calories and the latter (RCE%) to an optimal value of 150 total calories. Total
      energy intake was planned on the RCT% (RCP% + RCE%). We studied 75 VLBW infants
      with a mean BW of 1040 g and a mean GA of 29.5 weeks. The mean duration of PN was
      25.8 +/- 10.4 days. The initial weight loss (10.2 +/- 5.3%), the time to regain
      BW (5.5 +/- 4 days) and the day of lowest weight (5.2 +/- 1.6 day of life) were
      in the normal range; the subsequent growth rate resulted 25.9 +/- 9.2 g/kg/die
      and did not change for different GA or BW. Growth pattern about head
      circumference and length were above the third percentile. The mean age of RCT% =
      100% was 11.4 +/- 4.8 days of PN; this value was higher for the more premature
      infants. Severe metabolic abnormalities were not detected. Our observations show
      the efficacy of the RCT% as index of energy from both enteral and parenteral
      source during PN: the growth pattern seems to be quite satisfactory without any
      severe metabolic complication.

PMID- 7808361
TI  - [Short-chain fatty acids in the colon].

PMID- 7808363
TI  - [High incidence of Helicobacter pylori infections in an endoscopic pediatric
      patient series].
AB  - We evaluated in children with abdominal complaints the prevalence of Helicobacter
      pylori gastric and duodenal colonization and the histological features of gastric
      and duodenal mucosae. Fifty patients, aged 1-17 years, underwent upper endoscopy
      for recurrent abdominal pain, vomiting and/or gastrointestinal bleeding. With
      serological, bacteriological and/or histological methods twenty-eight children
      were demonstrated to be Helicobacter pylori-positive. No statistically
      significant differences were observed with regard to age, sex and indication to
      perform endoscopy. Eighty-two percent of Helicobacter pylori-positive patients
      had gastritis and/or duodenitis. The Helicobacter pylori-positive children had
      higher Helicobacter pylori specific IgG levels than the Helicobacter pylori
      negative ones (p < 0.001). No statistically significant differences were found
      between Helicobacter pylori-positive and Helicobacter pylori-negative subjects,
      for gastrin and pepsinogen I. Since the frequency of Helicobacter pylori
      infection in children with gastrointestinal complaints is high, in patients
      undergoing upper endoscopy, the sistematical examination of bioptic samples for
      bacteriological and histologic procedures is of great importance.

PMID- 7808364
TI  - [Primary enuresis in children. Which treatment today?].
AB  - Nowadays enuresis is a problem that pediatric urologists are often called to
      treat, since it affects 15 to 30% of school-age children. In 85% of affected
      children bedwetting is monosymptomatic, not accompanied by other voiding
      disorders or daytime incontinence. Treatment of choice is still highly
      controversial, as the physiopathology is not yet fully understood and the
      pathogenesis is multifactorial: genetic and psychological factors, sleep
      disorders, urinary reservoir abnormalities, urine production disorders can all
      play a part. Behavioural treatments (psychotherapy, bladder training and
      biofeedback, electric alarm) and pharmacological therapy (tricyclic
      antidepressants, anticholinergics, DDAVP) have been used with variable results.
      In our 1 year experience (54 enuretic children) DDAVP proved to be effective in
      reducing the number of wet nights per week in 79% of cases. Acupuncture, which we
      have been using for many years, also gave good results in 55% of treated
      patients. Long term success of DDAVP and acupuncture was respectively 50 and 40%.
      We discuss the probable pathophysiology and present our own results and those
      reported in the literature. It has to be stressed that an accurate diagnostic
      selection of patients and a better understanding of physiopathology are the basis
      of effective treatment of enuresis.

PMID- 7808365
TI  - [Cognitive and affective aspects of psychomotor assessment of myodystrophic
      children with the aim of specific treatment].
AB  - The aim of this study was to evaluate the incidence of cognitive and affective
      problems in the treatment of children suffering from myodystrophy. It was
      hypothesised that psychomotory assessment taking appropriate account of data
      regarding the evaluation of cognitive and affective development might allow an
      adequate and realistic therapeutic protocol to be defined. For this purpose the
      authors examined 55 myodystrophic patients aged between 6 and 10 years old during
      the period January 1980 and June 1993 using traditional psychomotory tests
      (Stanford-Binet and/or WISC in relation to the various age groups), projective
      tests (CAT, TAT) and graphic tests. The latter were also evaluated according to
      Koppitz's criterion which enabled emotional indicators (EI) to be assessed. All
      55 cases were evaluated in collaboration with the 1st Pediatric Clinic of the
      Neuro-Psychomotory Unit of "G. Gaslini" Institute. Psychomotory treatment, which
      by definition is addressed to the entire person, specifically took cognitive and
      affective data into consideration. In fact, as observed by Johnson and Alexander,
      in myodystrophy functional skills are more often limited by cognitive and
      motivational factors than by actual menomation. The results showed that the
      concentration on psychological aspects in the rehabilitation of myodystrophic
      children allows the neuropsychological component of movement (practognosia) to be
      preserved for as long as possible despite the progress of instrumental deficit
      (anatomic degeneration). In the authors' experience and in comparison to that of
      other Authors, it was possible to state that a "personalized" approach allows the
      subjects to improve their own "presence in the world".

PMID- 7808366
TI  - [Jarcho-Levin syndrome. Description of a clinical case with familial 14;21
      translocation].
AB  - The authors report the case of a child born at the Fatebenefratelli Hospital in
      Benevento with spondylo-costal dysplasia (SCD). SCD ia a rare association of
      vertebral and costal anomalies which was first described in 1938 by Jarcho and
      Levin. The fundamental characteristic of SCD is the anomalous nature of the
      vertebrae and ribs and, for this reason, subjects affected by SCD are above all
      short stature and present major physical malformations. In genetic terms, the
      pathology can be subdivided into three sub-groups based on the type of
      transmission: a) a dominant autosomic form, benign evolution; b) a recessive
      autosomic form, very severe; c) a recessive autosomic version with a relatively
      benign evolution. The case in question concerned a newborn suffering from severe
      bodily disharmony with dysmorphic features. Family medical history only showed
      diabetes mellitus and kyphoscoliosis in the paternal grandfather. The
      physiological anamnesis was completely negative (born at term, elective cesarean
      section) except for the fact that the mother had received estroprogestin therapy
      between the 2nd and 5th month of pregnancy due to partial placenta previa. The
      radiographic examination of the skeleton showed profound alterations of the
      vertebral column due to the presence of numerous hemispondyls, multiple costal
      malformations with segmentary synostosis and brachycephaly.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7808367
TI  - [Muscle phosphorylase deficiency in childhood. A case report].
AB  - Myophosphorylase deficiency or McArdle's disease is rarely recognized in
      childhood. The onset is generally in adolescence or in adult age with exercise
      intolerance, muscle cramps and myoglobinuria. Two siblings of 6 and 2 years of
      age are described. The first patient showed early fatigue and both had elevated
      CK levels. Morphological and biochemical studies of muscle biopsies revealed a
      defect of myophosphorylase.

PMID- 7808368
TI  - [Use of cyclosporin and verapamil in association with chemotherapy in the
      treatment of pediatric patients with advanced-stage neoplasms. A pilot study].
AB  - Multidrug resistance represents one of the most important factors that may lead
      to a therapeutic failure in some patients affected by malignancies. One of the
      best known mechanisms is linked to the genic amplification or the overproduction
      of a membrane glycoprotein, GP170, that is the product of the gene MDR1. The
      existence of drugs (calcium blockers, cyclosporine, tamoxifen, reserpine,
      quinidine) able to bind themselves to gp170 and to paralyze its activity in vitro
      is well known. We studied 20 pediatric patients (median age 9 years) affected by
      acute lymphoblastic leukemia (ALL), osteosarcoma, neuroblastoma and
      medulloblastoma, in advanced stage of disease. We employed in all cases the
      association of cytostatics with verapamil (50-70 mg/m2 i.v.) and cyclosporine (5
      8 mg/kg i.v.) with different infusion schedules. In leukemias we administered
      vincristine (1.5 mg/m2), and daunomycin (40 mg/m2), in solid tumors VP16 (150
      mg/m2) and adriamycin (60 mg/m2). Seventy-two therapeutic courses were performed:
      39 in ALL, 16 in osteosarcoma, 16 in neuroblastoma and 1 in medulloblastoma. On
      the whole 5 complete remissions were achieved in ALL patients and 1 in an
      osteosarcoma patient. We did not observe a significant myelosuppression during
      treatment, therefore few infectious complications occurred; furthermore
      electrocardiographic changes have been mild and promptly resolved after temporary
      discontinuation of verapamil infusion. Our data suggest a synergy of verapamil
      and cyclosporine in the inhibition of multidrug resistance induced by gp170,
      without the occurrence of heavy toxicity. The results obtained in ALL patients
      are encouraging., especially in view of a possible subsequent bone marrow
      transplantation, while in solid tumors they are not as satisfying.

PMID- 7808369
TI  - [Group A beta-hemolytic Streptococcus carrier state].

PMID- 7808370
TI  - Academic standards in nursing.

PMID- 7808371
TI  - Examination of student learning about dimensions of health and illness using
      Stewart's conceptual framework for primary health care.
AB  - In view of the increasing emphasis on community-based primary health care,
      nursing education programs need to identify creative learning strategies to
      prepare nurses capable of promoting, maintaining and restoring health in diverse
      populations. The purpose of this descriptive study was to identify the learning
      outcomes acknowledged by junior baccalaureate nursing students in non-traditional
      community settings. Data were gathered through semi-structured interviews with
      the students, through journals kept daily by the students, and from the faculty
      tutor's anecdotal notes. Analysis of data illustrated concepts from Stewart's
      conceptual framework for primary health care. Students gained an appreciation of
      the influence of the social-cultural-political and physical environments on
      health. They also came to understand the significance of collaborative modes of
      interaction with recipients of nursing care. Thus, non-traditional community
      experiences demonstrated effectiveness in enhancing students' understanding of
      the multiple dimensions of health as well as the necessity for mutuality in nurse
      person interactions. Providing varied learning environments in undergraduate
      nursing programs will produce practitioners who are more responsive to present
      and future primary health care issues.

PMID- 7808372
TI  - The Clinical Learning Spiral: a model to develop reflective practitioners.
AB  - Reflective practice in clinical nursing is an exciting concept. Much of the
      literature on reflection has been derived from education. Recently the
      Australasian Nurse Registering Authority Committee (ANRAC) endorsed reflective
      practice as a registering prerequisite competency for beginning nurse
      practitioners. This paper examines the concept and development of an action
      research clinical learning spiral to foster reflective practice of both
      undergraduate students and their clinical teacher in the practice setting. The
      innovation of a mutual group, that is, teacher and students interacting through
      reflection to create a co-operative learning environment is explored. In
      designing the spiral a number of models were consulted and incorporated. The
      action research clinical learning spiral adds structure and focus to the process
      of reflection-on-action and provides an avenue for students and the clinical
      teacher to set mutual goals of action to trial for future experiences. This
      process of reflection allows the clinical facilitator to be an integral component
      of success to the students learning in the clinical context.

PMID- 7808373
TI  - Students' evaluation of the process of conducting a patient assessment.
AB  - A Qualitative Evaluation Strategy was adopted to explore an early curriculum
      experience of undergraduate pre-registration student nurses. Open-ended
      narratives, in the style of Illuminative Evaluation (Parlett & Hamilton 1972),
      were used to encourage students to reflect upon their experience of conducting
      their first patient assessment using a model of nursing. A content analysis of
      the students' reflections is presented and discussed with reference to studies
      whose findings they corroborate and support. Aspects of the learning experience
      which influence the development of nursing skills were elucidated, together with
      the learning processes involved in the acquisition of patient assessment skills.
      Evaluating the context of the students' learning environment revealed some of the
      realities of learning nursing 'in the field', a lack of role models in clinical
      areas and the persistence of a theory-practice gap. In addition, this study shed
      light on the process of professional socialisation in student nurses. Encouraging
      reflection helped the students recognise how much they had learnt, and enabled us
      to evaluate our effectiveness as learning facilitators. An electic approach
      combining both qualitative and quantitative paradigms is advocated for holistic
      evaluation of the curriculum. Inferences from this evaluation may have particular
      relevance for designers and teachers of Project 2000 style courses.

PMID- 7808374
TI  - Designing an integrated curriculum with a common core for an inter-disciplinary
      course in community nursing.
AB  - This paper presents a curriculum model for inter-disciplinary courses in
      community nursing. The concern that the development of these courses could
      produce a generic nurse, resulting in the loss of specialist skills and knowledge
      from nurse practice is addressed. The argument is made, that by examining the
      field of practice and the field of study of the various nurse groups, it is
      possible to design a curriculum which will ensure that what is distinct and
      special for each nurse group can be maintained, developed and extended, within an
      inter-disciplinary course. The field of practice examined here is community
      nursing, but the principles of curriculum design should be equally relevant to
      all the nursing profession.

PMID- 7808375
TI  - Australian nursing--moving forward? Competencies and the nursing profession.
AB  - The introduction of national competencies for registration as a nurse in
      Australia has been met with great enthusiasm. While this development clearly
      brings some positive benefits the authors believe that competencies and
      competency development must be carefully monitored if Australian nurses are to
      avoid some of the pitfalls associated with this approach.

PMID- 7808376
TI  - Nurse teachers in higher education--without clinical competence, do they have a
      future?
AB  - The practice-theory divide between that which is taught in the classroom and
      which is performed in practice, is well documented. The role of the Registered
      Clinical Nurse Teacher was an attempt to overcome this, which failed. In many
      areas practitioners are being encouraged to become more educationally aware.
      However, many of the institutions which influence nursing in the United Kingdom
      expect teachers to be more clinically aware. This has led to a debate about the
      level of clinical competence or credibility a teacher requires. In this paper,
      two methods of achieving this are examined. First, the role of the Lecturer
      Practitioner, which provides clinical competence for a minority but which may not
      be appropriate for the majority, and can lead to isolation from other teachers.
      Second, the role of Link Teacher, which can provide clinical credibility, but
      where there are several reasons why the role is not being fulfilled adequately.
      The impending changes in the organisation of nurse education will affect teachers
      ability to bridge the practice-theory divide, as has already occurred in America.
      It is suggested that the role of the nurse teacher in the UK is being eroded by
      highly qualified specialists in higher education and more knowledgeable,
      articulate practitioners. Teachers need to establish their unique role which must
      lie in showing how academic knowledge can be integrated and applied to nursing
      practice. However, if nurse teachers do not maintain their clinical ability they
      will not be able to support their claim to do this, and not only will the
      practice-theory divide increase, but in the very near future nurse teachers will
      find it extremely difficult to justify their existence.

PMID- 7808377
TI  - Sculpting with people--an educational experience.
AB  - This paper explores the technique known as 'sculpting' and examines its
      application to the education of nurses. It identifies the therapeutic origins of
      sculpting, the processes and techniques involved and other requirements necessary
      for its application to nurse education. The experiences of both facilitator and
      participant are also described. It is argued that experiential learning methods
      in many cases continue to be met with anxiety and distrust often being carried
      out by facilitators who lack the skill and expertise to provide for the
      psychological safety of participants. The neglect or improper use of experiential
      learning methods denies students a valuable 'educational experience'.

PMID- 7808378
TI  - Nurse education and the impact of professionalisation.
AB  - This article asks what kind of educational process nurse education can follow.
      Educational theory offers two views; the rationalist and the humanist
      perspectives. Both involve problems for nurse education. Professionalisation is
      identified as the major force determining the educational process in nurse
      education. It prevents progressive humanist education and reinforces traditional
      rationalist education. This process continues with integration into higher
      education. Professionalisation must be abandoned as an occupational strategy, if
      an alternative educational process is to be developed in nurse education.

PMID- 7808379
TI  - It's not over.

PMID- 7808380
TI  - Patterns of sedentary lifestyle in Missouri.
AB  - Sedentary lifestyle is a major modifiable risk factor for chronic disease in
      Missouri. Survey data was examined for the prevalence of sedentary lifestyle in
      Missouri. Sedentary lifestyle was higher among blacks, older adults, persons with
      lower levels of education or income, and obese persons. Based on the current
      trend, Missouri is unlikely to achieve the year 2000 objective of < or = 50%
      prevalence of sedentary lifestyle.

PMID- 7808381
TI  - Hyperbaric oxygen therapy.
AB  - Hyperbaric oxygen (HBO) therapy is defined as treatment in which a patient
      breathes 100% oxygen while under a pressure greater than one atmosphere. The
      efficacy of hyperbaric therapy is based on a reduction in volume of gas-filled
      spaces; and an elevation of the partial pressure of oxygen resulting in
      hyperoxygenation of perfused tissues. Multiple animal studies, clinical trials,
      and extensive clinical experience have produced a set of 12 indications for which
      HBO therapy may be beneficial.

PMID- 7808382
TI  - Doctors are people too.

PMID- 7808383
TI  - Dengue type 3 infection--Nicaragua and Panama, October-November 1994.
AB  - The geographic range and incidence of dengue virus activity in the Americas
      substantially increased from 1980 to 1994. During this period, all dengue
      activity in the Americas was associated with dengue serotypes 1, 2, and 4 (DEN-1,
      DEN-2, and DEN-4). On November 25, 1994, the Ministry of Health of Nicaragua
      announced the isolation of dengue type 3 (DEN-3) from two children hospitalized
      with minor hemorrhagic manifestations in Managua. Subsequently, DEN-3 virus was
      isolated from two persons with dengue fever in Panama. These cases represent the
      first isolation of DEN-3 from autochthonous cases in the Americas since 1977.
      This report describes these cases and dengue activity in Nicaragua and Panama and
      summarizes public health activities to control dengue fever in the Americas.

PMID- 7808384
TI  - Race-specific differences in influenza vaccination levels among Medicare
      beneficiaries--United States, 1993.
AB  - One national health objective for the year 2000 is to provide annual influenza
      vaccination to 60% of all noninstitutionalized, high-risk populations in the
      United States, (objective 20.11) (1). Since May 1, 1993, Medicare has reimbursed
      providers for the cost of influenza vaccine; reimbursement for the administration
      of the vaccine also has been provided for beneficiaries with part B coverage,
      which allows them to receive the vaccine without a copayment and without having
      to meet the annual deductible amount for part B reimbursement. Approximately 96%
      of all persons aged > or = 65 years in the United States have Medicare part B
      coverage (Health Care Financing Administration [HCFA], unpublished data, 1994).
      To characterize patterns of vaccine use by Medicare beneficiaries, HCFA and CDC
      estimated influenza vaccine use by Medicare beneficiaries during September
      December 1993. Because of disparities in vaccine use by race, this analysis
      focused on race-specific differences between blacks and whites. This report
      presents the findings of that analysis.

PMID- 7808385
TI  - Type B botulism associated with roasted eggplant in oil--Italy, 1993.
AB  - In August and October 1993, public health officials in Italy were notified of
      seven cases of type B botulism from two apparently unrelated outbreaks in
      different communities. Investigations were initiated by the Regional Health
      Observatory of Campania and the Italian National Institute of Health. This report
      summarizes the outbreak investigations, which indicated that illness was
      associated with eating commercially prepared roasted eggplant in oil.

PMID- 7808386
TI  - Adult blood lead epidemiology and surveillance--United States, third quarter
      1994.

PMID- 7808387
TI  - Multistate outbreak of viral gastroenteritis associated with consumption of
      oysters--Apalachicola Bay, Florida, December 1994-January 1995.
AB  - On January 3, 1995, the Florida Department of Health and Rehabilitative Services
      (HRS) was notified of an outbreak of acute gastroenteritis associated with eating
      oysters. The subsequent investigation by HRS has identified 34 separate clusters
      of cases, many of which were associated with oysters harvested during December 29
      31 from 13 Mile Area and Cat Point in Apalachicola Bay. Oysters were shipped to
      other states, but additional clusters of illness associated with these oysters
      have been reported only in Georgia. Most of these oysters were served steamed or
      roasted. This report summarizes the preliminary findings of the ongoing
      investigation of this outbreak.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7808388
TI  - Transposon mutagenesis of coryneform bacteria.
AB  - The Corynebacterium glutamicum insertion sequence IS31831 was used to construct
      two artificial transposons: Tn31831 and miniTn31831. The transposition vectors
      were based on a gram-negative replication origin and do not replicate in
      coryneform bacteria. Strain Brevibacterium flavum MJ233C was mutagenized by
      miniTn31831 at an efficiency of 4.3 x 10(4) mutants per microgram DNA. Transposon
      insertions occurred at different locations on the chromosome and produced a
      variety of mutants. Auxotrophs could be recovered at a frequency of approximately
      0.2%. Transposition of IS31831 derivatives led not only to simple insertion, but
      also to cointegrate formation (5%). No multiple insertions were observed.
      Chromosomal loci of B. flavum corresponding to auxotrophic and pigmentation
      mutants could be rescued in Escherichia coli, demonstrating that these
      transposable elements are useful genetic tools for studying the biology of
      coryneform bacteria.

PMID- 7808390
TI  - Transcriptional activation of flanking sequences by Tn1000 insertion.
AB  - The carotenoid biosynthesis operon of Erwinia herbicola Eho13 consists of five
      genes, which are organized in the order crtE-crtX-crtY-crtI-crtB. These genes,
      with the exception of crtX, encode functions of beta-carotene biosynthesis and
      give an orange-coloured phenotype in Escherichia coli. Since crtX is not involved
      in the biosynthesis of beta-carotene, deletion of this gene does not alter the
      phenotype of pigmented cells. On the other hand, insertion of Tn1000 into crtX or
      into the upstream untranslated region of the operon resulted in a light-yellow,
      rather than an unpigmented phenotype, indicating that Tn1000 does not exert a
      strong polar effect when inserted in this operon. RNA analysis revealed that the
      sequence downstream from the insertion site was transcribed at a low level.
      Primer extension showed that the "-35"-like sequence in the terminal inverted
      repeats was not responsible for the transcription of the downstream sequence.
      Furthermore, primer extension and polymerase chain reaction (PCR) studies
      revealed that RNA transcribed from the promoters inside of Tn1000 was extended
      through the terminal inverted repeats into the adjacent sequences. In addition
      Tn1000, in either orientation, was able to generate fusion transcripts when
      placed upstream of a promoter-less tetracycline-resistance gene and resulted in
      cells resistant to the drug. These results showed that Tn1000 insertion
      transcriptionally activates the DNA sequences adjacent to the transposon.

PMID- 7808391
TI  - Quantitative trait loci (QTLs) for pollen thermotolerance detected in maize.
AB  - Pollen thermotolerance is an important component of the adaptability of crops to
      high temperature stress. The tolerance level of the different genotypes in a
      population of 45 maize recombinant inbred lines was determined as the degree of
      injury caused by high temperature to pollen germinability (IPGG) and pollen tube
      growth (IPTG) in an in vitro assay. Both traits revealed quantitative variability
      and high heritability. The traits were genetically dissected by the analysis of
      molecular markers using 184 mapped restriction fragment length polymorphisms
      (RFLPs). Significant genetic correlation between the markers and the trait
      allowed us to identify a minimum number of five qualitative trait loci (QTLs) for
      IPGG and six QTLs for IPTG. Their chromosomal localization indicated that the two
      characters are controlled by different sets of genes. In addition, IPGG and IPTG
      were shown to be basically independent of the pollen germination ability and
      pollen tube growth rate under non-stress conditions. These results are discussed
      in relation to their possible utilization in a breeding strategy for the
      improvement of thermotolerance in maize.

PMID- 7808389
TI  - Functional assignment of Erwinia herbicola Eho10 carotenoid genes expressed in
      Escherichia coli.
AB  - Erwinia herbicola is a nonphotosynthetic bacterium that is yellow pigmented due
      to the presence of carotenoids. When the Erwinia carotenoid biosynthetic genes
      are expressed in Escherichia coli, this bacterium also displays a yellow
      phenotype. The DNA sequence of the plasmid pPL376, carrying the entire Erwinia
      carotenoid gene cluster, has been found to contain 12 open reading frames (ORFs).
      Six of the ORFs have been identified as carotenoid biosynthesis genes that code
      for all the enzymes required for conversion of farnesyl pyrophosphate (FPP) to
      zeaxanthin diglucoside via geranylgeranyl pyrophosphate, phytoene, lycopene, beta
      carotene, and zeaxanthin. These enzymatic steps were assigned after disruption of
      each ORF by a specific mutation and analysis of the accumulated intermediates.
      Carotenoid intermediates were identified by the absorption spectra of the colored
      components and by high pressure liquid chromatographic analysis. The six
      carotenoid genes are arranged in at least two operons. The gene coding for beta
      carotene hydroxylase is transcribed in the opposite direction from that of the
      other carotenoid genes and overlaps with the gene for phytoene synthase.

PMID- 7808393
TI  - Transposition of Tnr1 in rice genomes to 5'-PuTAPy-3' sites, duplicating the TA
      sequence.
AB  - Tnr1 is a repetitive sequence in rice with several features characteristic of a
      transposable DNA element. Its copy number was estimated to be about 3500 per
      haploid genome by slot-blot hybridization. We have isolated six members of Tnr1
      located at different loci by PCR (polymerase chain reaction) and determined their
      nucleotide sequences. The Tnr1 elements were similar in size and highly
      homologous (about 85%) to the Tnr1 sequence identified first in the Waxy gene in
      Oryza glaberrima. A consensus sequence of 235 bp could be derived from the
      nucleotide sequences of all the Tnr1 members. The consensus sequence showed that
      base substitutions occurred frequently in Tnr1 by transition, and that Tnr1 has
      terminal inverted repeat sequences of 75 bp. Almost all the chromosomal sequences
      that flank the Tnr1 members were 5'-PuTA-3' and 5'-TAPy-3', indicating that Tnr1
      transposed to 5'-PuTAPy-3' sites, duplicating the TA sequence. PCR-amplified
      fragments from some rice species did not contain the Tnr1 members at
      corresponding loci. Comparison of nucleotide sequences of the fragments with or
      without a Tnr1 member confirmed preferential transposition of Tnr1 to 5'-PuTAPy
      3' sites, duplicating the TA sequence. One amplified sequence suggested that
      imprecise excision had occurred to remove a DNA segment containing a Tnr1 member
      and its neighboring sequences at the Waxy locus of rice species with genome types
      other than AA. We also present data that may suggest that Tnr1 is a defective
      form of an autonomous transposable element.

PMID- 7808394
TI  - Involvement of transposition in dispersion of tandem repeat sequences (TrsA) in
      rice genomes.
AB  - We describe a method to identify and characterize DNA fragments containing the
      junction of AA genome-specific tandem repeat sequences (here called TrsA) with
      adjacent chromosomal sequences of rice by the polymerase chain reaction (PCR)
      using a pair of primers that hybridize with TrsAs and a flanking non-TrsA
      sequence. With this method, we obtained results suggesting that TrsA sequences
      present at two loci (here called trsA1 and trsA2) are flanked by direct repeats
      of chromosomal sequences of 172 bp and about 440 bp in length, respectively.
      These results support the idea that the TrsA sequences have been inserted into
      each locus by transposition, resulting in duplication of the chromosomal sequence
      used as target. We also describe a method to identify and characterize TrsA
      sequences repeated in only a few copies in the rice genome by PCR, using a pair
      of primers that hybridize with two different portions in the TrsA sequence, and
      demonstrate that TrsA sequences are present not only in rice strains with the AA
      genome, but also in those with non-AA genomes. The TrsA sequences were present at
      the trsA1 locus in all the rice strains examined, indicating that TrsA was
      inserted and amplified at the locus before the divergence of the various species
      of rice in the Oryza genus. TrsA sequences were present at the trsA2 locus,
      however, only in an O. sativa IR36 strain, indicating that TrsA was inserted and
      amplified at this locus during divergence of rice strains with the AA genome.

PMID- 7808392
TI  - Identification and preliminary characterization of temperature-sensitive
      mutations affecting HlyB, the translocator required for the secretion of
      haemolysin (HlyA) from Escherichia coli.
AB  - We have carried out a genetic analysis of Escherichia coli HlyB using in
      vitro(hydroxylamine) mutagenesis and regionally directed mutagenesis. From random
      mutagenesis, three mutants, temperature sensitive (Ts) for secretion, were
      isolated and the DNA sequenced: Gly10Arg close to the N-terminus, Gly408Asp in a
      highly conserved small periplasmic loop region PIV, and Pro624Leu in another
      highly conserved region, within the ATP-binding region. Despite the Ts character
      of the Gly10 substitution, a derivative of HlyB, in which the first 25 amino
      acids were replaced by 21 amino acids of the lambda Cro protein, was still active
      in secretion of HlyA. This indicates that this region of HlyB is dispensable for
      function. Interestingly, the Gly408Asp substitution was toxic at high temperature
      and this is the first reported example of a conditional lethal mutation in HlyB.
      We have isolated 4 additional mutations in PIV by directed mutagenesis, giving a
      total of 5 out of 12 residues substituted in this region, with 4 mutations
      rendering HlyB defective in secretion. The Pro624 mutation, close to the Walker B
      site for ATP binding in the cytoplasmic domain is identical to a mutation in HisP
      that leads to uncoupling of ATP hydrolysis from the transport of histidine. The
      expression of a fully functional haemolysin translocation system comprising
      HlyC,A,B and D increases the sensitivity of E. coli to vancomycin 2.5-fold,
      compared with cells expressing HlyB and HlyD alone. Thus, active translocation of
      HlyA renders the cells hyperpermeable to the drug. Mutations in hlyB affecting
      secretion could be assigned to two classes: those that restore the level of
      vancomycin resistance to that of E. coli not secreting HlyA and those that still
      confer hypersensitivity to the drug in the presence of HlyA. We propose that
      mutations that promote vancomycin resistance will include mutations affecting
      initial recognition of the secretion signal and therefore activation of a
      functional transport channel. Mutations that do not alter HlyA-dependent
      vancomycin sensitivity may, in contrast, affect later steps in the transport
      process.

PMID- 7808395
TI  - Characterization and expression of a P-450-like mycinamicin biosynthesis gene
      using a novel Micromonospora-Escherichia coli shuttle cosmid vector.
AB  - A 29 kb shuttle cosmid vector, pTYS507, was constructed from a cryptic
      Micromonospora griseorubida plasmid and the Escherichia coli cosmid pJB8.
      Subcloning of mycinamicin II biosynthesis genes in pTYS507 led to the
      identification of a DNA region that could complement a mutant of M. griseorubida
      that lacked both hydroxylase and epoxidase activities. Nucleotide sequence and
      mutational analysis suggested that a single P-450-like protein catalyzes both
      reactions.

PMID- 7808396
TI  - Expression of a reporter gene is reduced by a ribozyme in transgenic plants.
AB  - A chimeric gene encoding a ribozyme under the control of the cauliflower mosaic
      virus (CaMV) 35S promoter was introduced into transgenic tobacco plants. In vivo
      activity of this ribozyme, which was designed to cleave npt mRNA, was previously
      demonstrated by transient expression assays in plant protoplasts. The ribozyme
      gene was transferred into transgenic tobacco plants expressing an rbcS-npt
      chimeric gene as an indicator. Five double transformants out of sixteen exhibited
      a reduction in the amount of active NPT enzyme. To measure the amount of ribozyme
      produced, in the absence of its target, the ribozyme and target genes were
      separated by genetic segregation. The steady-state concentrations of ribozyme and
      target RNA were shown to be similar in the resulting single transformants. Direct
      evidence for a correlation between reduced npt gene expression and ribozyme
      expression was provided by crossing a plant containing only the ribozyme gene
      with a transgenic plant expressing the npt gene under control of the 35S
      promoter, i.e. the same promoter used to direct ribozyme expression. The
      expression of npt was reduced in all progeny containing both transgenes. Both
      steady-state levels of npt mRNA and amounts of active NPT enzyme are decreased.
      In addition, our data indicate that, at least in stable transformants, a large
      excess of ribozyme over target is not a prerequisite for achieving a significant
      reduction in target gene expression.

PMID- 7808397
TI  - Inheritance and expression of a transgene insert in an aneuploid tobacco line.
AB  - A T-DNA locus comprising nptII, uidA and nos genes--all under the control of the
      nos promoter (this locus was designated K because it encodes resistance to
      Kanamycin)--was found to be inherited erratically in a transgenic tobacco line.
      This anomalous behavior was partially explained following a karyotype analysis of
      plants representing several generations: these plants were aneuploids, presumably
      for the K-containing chromosome. During four generations of sexual propagation,
      transgenic plants that were either trisomic or tetrasomic for the K-containing
      chromosome (i.e. 2n = 49 or 2n = 50, respectively) were obtained. The trisomic
      plants (2n = 48 + 1) were virtually indistinguishable phenotypically from normal
      euploids (2n = 4x = 48), whereas the tetrasomic plants (2n = 48 + 2) were
      smaller, had somewhat misshapen leaves and exhibited reduced fertility. Although
      the amount of NPTII protein in different trisomic (K--, KK-, KKK) and tetrasomic
      (KK--, KKK-) plants was generally consistent with a K dosage effect, the genetic
      behavior of each trisomic--with respect to segregation of KanR and marker gene
      activity in progeny--was unique and not completely explicable by invoking
      aneuploidy. Specifically, unexpected gains or losses of K could occur, suggesting
      the formation of double reductional gametes and/or frequent gene conversion at
      this locus. The susceptibility of K locus marker genes to trans-inactivation in
      the trisomic and tetrasomic lines was tested by crossing in partially homologous
      silencing loci. In all transgenotypes tested, the three K marker genes were
      sensitive to trans-silencing, which was accompanied by methylation in all copies
      of the nos promotor. In addition to this directed inactivation/methylation, the K
      locus could also undergo infrequent, spontaneous partial methylation, which
      produced stable epialleles. In most plants, however, the multiple copies of the
      nos promoter at this locus remained unmethylated and active through four
      generations in all transgenotypes examined. The significance of these results for
      irregular inheritance patterns, aneuploid syndromes and homology-dependent gene
      silencing is discussed.

PMID- 7808398
TI  - The frequency of MMS-induced, umuDC-dependent, mutations declines during
      starvation in Escherichia coli.
AB  - It has been found that the level of methyl methanesulfonate (MMS)-induced
      mutation in Escherichia coli is dependent on the level of UmuD(D')C proteins. The
      frequency of argE(ochre)-->Arg+ mutations (which occur predominantly by AT-->TA
      transversions) and RifS-->RifR mutations is much higher when UmuDC or UmuD'C are
      overproduced in the cell. When MMS-treated bacteria were starved for
      progressively longer times and hence the expression of mutations delayed, the
      level of mutations observed progressively declined. This same treatment had no
      effect on the degree of SOS induction. Examination of plasmid DNAs, isolated from
      MMS-treated cells, for their sensitivity to the specific endonucleases Fpg and
      Nth revealed that MMS causes formation of abasic sites, which are repaired during
      cell starvation. It is assumed that, in non-dividing cells, apurinic sites are
      mostly repaired by RecA-mediated recombinational repair. This pathway, which is
      error-free, is compared with the processing pathway in metabolically active
      cells, where translesion synthesis by the UmuD'2C-RecA-DNA polymerase III
      holoenzyme complex occurs; this latter pathway is error-prone.

PMID- 7808399
TI  - Agrobacterium vitis nopaline Ti plasmid pTiAB4: relationship to other Ti plasmids
      and T-DNA structure.
AB  - The Ti plasmid of the Agrobacterium vitis nopaline-type strain AB4 was subcloned
      and mapped. Several regions of the 157 kb Ti plasmid are similar or identical to
      parts of the A. vitis octopine/cucumopine (o/c)-type Ti plasmids, and other
      regions are homologous to the nopaline-type Ti plasmid pTiC58. The T-DNA of
      pTiAB4 is a chimaeric structure of recent origin: the left part is 99.2%
      homologous to the left part of the TA-DNA of the o/c-type Ti plasmids, while the
      right part is 97.1% homologous to the right part of an unusual nopaline T-DNA
      recently identified in strain 82.139, a biotype II strain from wild cherry. The
      3' noncoding regions of the ipt genes from pTiAB4 and pTi82.139 are different
      from those of other ipt genes and contain a 62 bp fragment derived from the
      coding sequence of an ipt gene of unknown origin. A comparison of different ipt
      gene sequences indicates that the corresponding 62 bp sequence within the coding
      region of the AB4 ipt gene has been modified during the course of its evolution,
      apparently by sequence transfer from the 62 bp sequence in the 3' non-coding
      region. In pTi82.139 the original coding region of the ipt gene has remained
      largely unmodified. The pTiAB4 6b gene differs from its pTi82.139 counterpart by
      the lack of a 12 bp repeat in the 3' part of the coding sequence. This leads to
      the loss of four glutamic acid residues from a series of ten. In spite of these
      differences, the ipt and 6b genes of pTiAB4 are functional. Our results provide
      new insight into the evolution of Agrobacterium Ti plasmids and confirm the
      remarkable plasticity of these genetic elements. Possible implications for the
      study of bacterial phylogeny are discussed.

PMID- 7808400
TI  - The yeast protein Gcr1p binds to the PGK UAS and contributes to the activation of
      transcription of the PGK gene.
AB  - Analysis of the upstream activation sequence (UAS) of the yeast phosphoglycerate
      kinase gene (PGK) has demonstrated that a number of sequence elements are
      involved in its activity and two of these sequences are bound by the
      multifunctional factors Rap1p and Abf1p. In this report we show by in vivo
      footprinting that the regulatory factor encoded by GCR1 binds to two elements in
      the 3' half of the PGK UAS. These elements contain the sequence CTTCC, which was
      previously suggested to be important for the activity of the PGK UAS and has been
      shown to be able to bind Gcr1p in vitro. Furthermore, we find that Gcr1p
      positively influences PGK transcription, although it is not responsible for the
      carbon source dependent regulation of PGK mRNA synthesis. In order to mediate its
      transcriptional influence we find that Gcr1p requires the Rap1p binding site, in
      addition to its own, but not the Abf1p site. As neither a Rap1p nor a Gcr1p
      binding site alone is able to activate transcription, we propose that Gcr1p and
      Rap1p interact in an interdependent fashion to activate PGK transcription.

PMID- 7808402
TI  - Solanum brevidens possesses a non-sucrose-inducible patatin gene.
AB  - The patatin gene is the best known "tuber-specific" gene of potato (Solanum
      tuberosum). Patatin is encoded by a multigene family that can be divided into two
      classes. Class I genes are highly expressed in tubers and are sucrose inducible,
      while class II genes are under developmental control and are expressed mainly in
      root tips. Here we report the isolation and characterization of cDNA clones
      corresponding to a patatin gene of the non-tuberizing Solanum species S.
      brevidens. We show that the gene is 94-100% homologous to the class I type
      patatin genes of S. tuberosum; the homology includes the sequences in the 5' and
      the 3' untranslated regions. However, the patatin gene of S. brevidens is
      regulated like class II type patatin genes and cannot be transcriptionally
      activated by elevated levels of sucrose. This result further supports the idea
      that the components required for tuberization may be present in non-tuberizing
      solanaceous plants, but are regulated differently.

PMID- 7808401
TI  - DNA binding site specificity of the Neurospora global nitrogen regulatory protein
      NIT2: analysis with mutated binding sites.
AB  - NIT2, a positive-acting regulatory protein in Neurospora crassa, activates the
      expression of a series of unlinked structural genes that encode nitrogen
      catabolic enzymes. NIT2 binding sites in the promoter regions of nit3, alc and
      lao have at least two GATA sequence elements. We have examined the binding
      affinity of the NIT2 protein for the yeast DAL5 wild-type upstream activation
      sequence UASNTR, which contains two GATA elements, and for a series of mutated
      binding sites, each differing from the wild-type site by a single base.
      Substitution for individual nucleotides within 5' or 3' sequences that flank the
      GATA elements had only modest effects upon NIT2 binding. In contrast, nearly all
      substitutions within the GATA elements almost completely eliminated NIT2 binding,
      demonstrating the importance of the GATA sequence for NIT2 binding. Four high
      affinity binding sites for the NIT2 protein were found within a central region of
      the nit-2 gene itself.

PMID- 7808404
TI  - A genetic approach to the identification of functional amino acids in protein p6
      of Bacillus subtilis phage phi 29.
AB  - Protein p6 of the Bacillus subtilis phage phi 29 is essential for in vivo viral
      DNA replication. This protein activates the initiation of phi 29 DNA replication
      in vitro by forming a multimeric nucleoprotein complex at the replication
      origins. The N-terminal region of protein p6 is involved in DNA binding, as shown
      by in vitro studies with p6 proteins altered by deletions or missense mutations.
      We report on the development of an in vivo functional assay for protein p6. This
      assay is based on the ability of protein p6-producing B. subtilis non-suppressor
      (su) cells to support growth of a phi 29 sus6 mutant phage. We have used this
      trans-complementation assay to investigate the effect on in vivo viral DNA
      synthesis of missense mutations introduced into the protein p6 N-terminal region.
      The alteration of lysine to alanine at position 2 resulted in a partially
      functional protein, whereas the replacement of arginine by alanine at position 6
      gave rise to an inactive protein. These results indicate that arginine at
      position 6 is critical for the in vivo activity of protein p6. Our
      complementation system provides a useful genetic approach for the identification
      of functionally important amino acids in protein p6.

PMID- 7808403
TI  - Interspecies regulation of the recA gene of gram-negative bacteria lacking an E.
      coli-like SOS operator.
AB  - The recA genes of Agrobacterium tumefaciens, Rhizobium meliloti, Rhizobium
      phaseoli and Rhodobacter sphaeroides, species belonging to the alpha-group
      bacteria of the Proteobacteria class, have been fused in vitro to the lacZ gene
      of Escherichia coli. By using a mini-Tn5 transposon derivative, each of these
      recA-lacZ fusions was introduced into the chromosome of each of the four species,
      and into that of E. coli. The recA genes of three of the alpha bacteria are
      induced by DNA damage when inserted in A. tumefaciens, R. phaseoli or R. meliloti
      chromosomes. The expression of the recA gene of R. sphaeroides is DNA damage
      mediated only when present in its own chromosome; none of the genes is induced in
      E. coli. Likewise, the recA gene of E. coli is not induced in any of the four
      alpha species. These data indicate that A. tumefaciens, R. meliloti and R.
      phaseoli possess a LexA-like repressor, which is able to block the expression of
      their recA genes, as well as that of R. sphaeroides, but not the recA gene of E.
      coli. The LexA repressor of R. sphaeroides does not repress the recA gene of A.
      tumefaciens, R. meliloti, R. phaseoli or E. coli.

PMID- 7808405
TI  - Synthesis of an unusual alpha-zein protein is correlated with the phenotypic
      effects of the floury2 mutation in maize.
AB  - The soft, starchy endosperm of the maize (Zea mays L.) floury 2 mutant is
      associated with a reduction in zein mRNA and protein synthesis, unique protein
      body morphology, and enhanced levels of a 70 kDa protein, that has been shown to
      be the maize homolog of a chaperonin found in the endoplasmic reticulum. We found
      an unusual alpha-zein protein of 24 kDa to be consistently associated with the
      zein fraction from floury 2 mutants. Three additional alpha-zein proteins with
      molecular weights ranging from ca. 25 to 27 kDa are detected in the storage
      protein fraction of a high percentage of floury 2 kernels and a low percentage of
      normal kernels in a genetically segregating population. The four proteins in a
      genetically segregating population. The four proteins can be distinguished from
      one another by immunostaining on Western blots. Synthesis of the 24 kDa protein
      is regulated by Opaque2, since the 24 kDa protein is lacking in the storage
      protein fraction of opaque2/floury2 double mutants. The synthesis of an abnormal
      alpha-zein protein in floury2 could explain many features of the mutant, such as
      the abnormal protein body morphology, induction of the 70 kDa chaperonin, and
      hypostasis to opaque2 (o2). Although we cannot prove that the accumulation of
      this protein is responsible for the floury2 phenotype, we were able to detect a
      restriction fragment length polymorphism (RFLP) linked to the floury2 locus with
      a 22 kDa alpha-zein probe. We hypothesize that the unique characteristics of the
      floury2 mutant could be a response to the accumulation of a defective alpha-zein
      protein which impairs secretory protein synthesis.

PMID- 7808406
TI  - QTL mapping of naturally-occurring variation in flowering time of Arabidopsis
      thaliana.
AB  - A segregating F2 population of Arabidopsis thaliana derived from a cross between
      the late-flowering ecotype Hannover/Munden (HM) and the early-flowering ectoype
      Wassilewskija (WS) was analyzed for flowering time and other morphological
      traits. Two unlinked quantitative trait loci (QTLs) affecting days to first
      flower (DFF-a and DFF-b) mapped to chromosome 5. QTLs which affect node number
      (NN), leaf length at flowering (LLF), and lead length at 35 days (LL35) also
      mapped to chromosome 5; LLF-a, LL35-a, NN-a map to the same region of chromosome
      5 as DFF-a; LLF-b and LL35-bmap to the same region of chromosome 5 as DFF-b.
      Another QTL affecting leaf length at flowering (LLF-c) maps to chromosome 3. The
      proximity of DFF-a, LLF-a, LL35-a and NN-a, as well as the similarity in gene
      action among these QTLs (additivity), suggest that they may be pleiotropic
      consequences of a single gene at this locus. Similarly, LL35-b and LLF-b map near
      each other and both display recessive gene action, again suggesting the
      possibility of pleiotropy. DFF-b, which also maps near LL35-b and LLF-b, displays
      largely additive gene action (although recessive gene action could not be ruled
      out). This suggests that DFF-b may represent a different gene from LL35-b and/or
      LLF-b. DFF-a maps near two previously identified mutants: co (which also affects
      flowering time and displays gene action consistent with additivity) and
      flc.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7808407
TI  - Structural and functional characterisation of the signal recognition particle
      specific 54 kDa protein (SRP54) of tomato.
AB  - Two representative genes for the 54 kDa protein subunit of the signal recognition
      particle (SRP54) of tomato were cloned. It was shown that both genes are
      expressed in the tomato cv. Rentita. SRP54 is encoded by nine exons distributed
      over 10 kb of genomic sequence. The amino acid sequences deduced for the two
      SRP54 genes are 92% identical and the calculated protein size is 55 kDa. Like the
      homologous proteins isolated from other eukaryotes, the tomato SRP54 is evidently
      divided into two domains. As deduced from sequence motif identity, the N
      terminally located G-domain can be assumed to have GTPase activity. The C
      terminal part of the protein is methionine rich (14% methionine) and represents
      the M-domain. In in vitro binding experiments, SRP54 of tomato was able to attach
      to the 7S RNA of tomato, its natural binding partner in the SRP. This interaction
      can only take place in a trimeric complex consisting of 7S RNA, SRP54 and SRP19.
      The latter protein subunit of the SRP complex is assumed to induce a
      conformational change in the 7S RNA. The human SRP19 was able to mediate the
      binding of the tomato SRP54 to the 7S RNA, irrespective of whether this latter
      originated from tomato or man.

PMID- 7808408
TI  - Retrotransposon-induced ectopic expression of the Om(2D) gene causes the eye
      specific Om(2D) phenotype in Drosophila ananassae.
AB  - Optic morphology (Om) mutations in Drosophila ananassae map to at least 22 loci,
      which are scattered throughout the genome. Om mutations are all semidominant,
      neomorphic, nonpleiotropic, and associated with the insertion of a
      retrotransposon, tom. We have found that the Om(2D) gene encodes a novel protein
      containing histidine/proline repeats, and is ubiquitously expressed during
      embryogenesis. The Om(2D) RNA is not detected in wild-type eye imaginal discs,
      but is abundantly found in the center of the eye discs of Om(2D) mutants, where
      excessive cell death occurs. D. melanogaster flies transformed with the Om(2D)
      cDNA under control of the hsp70 promoter display abnormal eye morphology when
      heat-shocked at the third larval instar stage. These results suggest that the
      Om(2D) gene is not normally expressed in the eye imaginal discs, but its ectopic
      expression, induced by the tom element, in the eye disc of third instar larvae
      results in defects in adult eye morphology.

PMID- 7808409
TI  - DPhK-gamma, a putative Drosophila kinase with homology to vertebrate
      phosphorylase kinase gamma subunits: molecular characterisation of the gene and
      phenotypic analysis of loss of function mutants.
AB  - Partial and total loss of function mutant alleles of a putative Drosophila
      homologue (DPhK-gamma) of the vertebrate phosphorylase kinase gamma-subunit gene
      have been isolated. DPhK-gamma is required in early embryonic processes, such as
      gastrulation and mesoderm formation; however, defects in these processes are seen
      only when both the maternal and zygotic components of DPhK-gamma expression are
      eliminated. Loss of zygotic expression alone does not appear to affect normal
      embryonic and larval development; some pupal lethality is observed but the
      majority of mutant animals eclose as adults. Many of these adults show defects in
      their leg musculature (e.g. missing and degenerating muscles), in addition to
      exhibiting melanised "tumours" on their leg joints. Loss of only the maternal
      component has no obvious phenotypic consequences. The DPhK-gamma gene has been
      cloned and sequenced. It has an open reading frame (ORF) of 1680 bp encoding a
      560 amino acid protein. The predicted amino acid sequence of DPhK-gamma has two
      conserved domains, the catalytic kinase and calmodulin-binding domains, separated
      by a linker sequence. The amino acid sequence of DPhK-gamma is homologous to that
      of mammalian PhK-gamma proteins but differs in the length and amino acid
      composition of its linker sequence. The expression of DPhK-gamma mRNA is
      developmentally regulated. We discuss the implications of these observations.

PMID- 7808410
TI  - Mapping a mutator, mu2, which increases the frequency of terminal deletions in
      Drosophila melanogaster.
AB  - A mutator, mu2, in Drosophila melanogaster has been identified recently that
      potentiates the recovery of terminal deficiencies. The deleted chromosomes behave
      as if they had been capped; that is, they are protected from degradation and from
      fusion with other chromosome fragments. The mutator maps near the telomere on the
      left arm of chromosome 3. Using the selectable marker Aprt, 150 deficiencies for
      region 62 of the cytological map have been recovered. These deficiencies identify
      the map position of mu2 as 62B11-C1. A yeast artificial chromosome spanning this
      region has been subcloned into lambda phage, and the positions of deficiency
      breakpoints on either side of the mu2 gene have been identified within the
      subclones. These positions limit the location of the left end of the gene to a 23
      kb region. In the course of these experiments, three additional, presumptive
      mutant alleles were identified, suggesting that other mutator alleles remain
      undiscovered in many standard laboratory stocks.

PMID- 7808411
TI  - Modification of the 5' untranslated leader region of the maize Activator element
      leads to increased activity in Arabidopsis.
AB  - In contrast to its behavior in tobacco and tomato, the maize transposable element
      Ac is relatively inactive in Arabidopsis. We show here that removal of 537 bp
      within a CpG-rich region of the Ac 5' untranslated leader region significantly
      increases the excision frequency of the element in Arabidopsis. This increase did
      not appear to be correlated with the removal of sequences that are methylated in
      inactive Ac elements in maize, as these sites were not methylated in Ac elements
      in Arabidopsis transformants. The deletion within the 5' untranslated leader did
      not increase Ac activity by increasing levels of steady-state transposase mRNA,
      as assayed by RNase protection experiments. Moreover, there was no correlation
      between the levels of steady-state transposase mRNA and Ac element activity. This
      suggests that post-transcriptional regulation of Ac activity occurs in
      Arabidopsis.

PMID- 7808412
TI  - Cytosolic and plastid forms of 5-enolpyruvylshikimate-3-phosphate synthase in
      Euglena gracilis are differentially expressed during light-induced chloroplast
      development.
AB  - The enzyme 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase (EC 2.5.1.19), the
      target of the herbicide glyphosate [N-(phosphonomethyl)glycine], exists in two
      molecular forms in Euglena gracilis. One form has previously been characterized
      as a monofunctional 59 kDa protein. The other form constitutes a single domain of
      the multifunctional 165 kDa arom protein. The two enzyme forms are inversely
      regulated at the protein and mRNA levels during light-induced chloroplast
      development, as demonstrated by the determination of their enzyme activities
      after non-denaturing polyacrylamide gel electrophoresis and Northern
      hybridization analysis with a Saccharomyces cerevisiae ARO1 gene probe. The arom
      protein and its mRNA predominate in dark-grown cells, and the levels of both
      decline upon illumination. In contrast, the monofunctional EPSP synthase and its
      mRNA are induced by light, the increase in mRNA abundance preceding accumulation
      of the protein. The two enzymes are localized in different subcellular
      compartments, as demonstrated by comparing total protein patterns with those of
      isolated organelles. Glyphosate-adapted wild-type cells and glyphosate-tolerant
      cells of a plastid-free mutant of E. gracilis, W10BSmL, were used for organelle
      isolation and protein extraction, as these cell lines overproduce EPSP synthase
      and the arom protein, respectively. Evidence was obtained for the cytosolic
      localization of the arom protein and the plastid compartmentalization of the
      monofunctional EPSP synthase. These conclusions are further supported by the
      observation that EPSP synthase precursor, produced by in vitro translation of the
      hybrid-selected mRNA, was efficiently taken up and processed to mature size by
      isolated chloroplasts from photoautotrophic wild-type E. gracilis cells, while
      the in vitro-synthesized arom protein was not sequestered by isolated Euglena
      plastids.

PMID- 7808413
TI  - Position and direction of strand exchange in bacteriophage HK022 integration.
AB  - The positions of the endonucleolytic cleavages promoted by the integrase protein
      (Int) of coliphage HK022 within its attB site were determined. The protein
      catalyses a staggered cut, which defines an overlap sequence of 7 bp within the
      core site. The overlap region is at the center of symmetry of a palindromic
      sequence which appears in all four putative att core binding sites for Int. We
      confirm that the order of strand exchange is similar to that in phage lambda.

PMID- 7808414
TI  - Analysis of a histone H2A variant from fission yeast: evidence for a role in
      chromosome stability.
AB  - We have isolated and characterised the pht1 gene from the fission yeast
      Schizosaccharomyces pombe. The sequence of the predicted translation product has
      revealed a striking similarity to the family of H2A.F/Z histone variant proteins,
      which have been found in a variety of different organisms. Cells deleted for the
      pht1 gene locus grow slowly, exhibit an altered colony morphology, increased
      resistance to heat shock and show a significant decrease in the fidelity of
      segregation of an S. pombe minichromosome. We propose that the histone H2A
      variant encoded by the pht1 gene is important for chromosomal structure and
      function, possibly including a role in controlling the fidelity of chromosomal
      segregation during mitosis.

PMID- 7808415
TI  - The homeotic Macho mutant of Antirrhinum majus reverts to wild-type or mutates to
      the homeotic plena phenotype.
AB  - Plants of Antirrhinum majus carrying the semidominant Macho alleles of the plena
      gene display carpelloid sepals and staminoid petals, but the two inner flower
      whorls of stamens and carpels are normal and produce fertile gametes. In the
      recessive plena mutant, in contrast, the two outer whorls are normal whereas the
      stamens are largely or entirely petaloid and the carpels sepaloid, thus producing
      weakly male-fertile or fully sterile lines. Two new plena and two new Macho
      alleles have been induced in transposon tagging experiments. Genetic and
      molecular analysis revealed that the two contrasting mutant phenotypes are caused
      by mutations in one and the same gene: Several wild-type plants appeared among
      27,000 F1 plants of a cross between Macho female plants and wild-type males
      bearing the active transposons Tam1 and Tam3. One of these plants segregated
      plena mutants, three showed reversions to wild-type and another two segregated
      Macho plants, possibly representing somatic reversions. Additional evidence was
      provided by an allelism test of Macho x plena. Molecular analysis has
      independently corroborated the genetical results. Moreover, the double mutant
      Macho/deficiens shows only carpels and plena/deficiens only sepals, which is in
      accord with combinatorial models for homeotic flower formation presented
      recently.

PMID- 7808416
TI  - Comparison of genetic and physical maps of group 7 chromosomes from Triticum
      aestivum L.
AB  - We present a high density physical map of homoeologous group 7 chromosomes from
      Triticum aestivum L. using a series of 54 deletion lines, 6 random amplified
      polymorphic DNA (RAPD) markers and 91 cDNA or genomic DNA clones from wheat,
      barley and oat. So far, 51 chromosome segments have been distinguished by
      molecular markers, and 54 homoeoloci have been allocated among chromosomes 7A, 7B
      and 7D. The linear order of molecular markers along the chromosomes is almost
      identical in the A- B- and D-genome of wheat. In addition, there is colinearity
      between the physical and genetic maps of chromosomes 7A, 7B and 7D from T.
      aestivum, indicating gene synteny among the Triticeae. However, comparison of the
      physical map of chromosome 7D from T. aestivum with the genetic map from Triticum
      tauschii some markers have been shown to be physically allocated with distortion
      in more distal chromosome regions. The integration of genetic and physical maps
      could assist in estimating the frequency and distribution of recombination in
      defined regions along the chromosome. Physical distance did not correlate with
      genetic distance. A dense map facilitates the detection of multiple
      rearrangements. We present the first evidence for an interstitial inversion
      either on chromosome arm 7AS or 7DS of Chinese Spring. Molecularly tagged
      chromosome regions (MTCRs) provide landmarks for long-range mapping of DNA
      fragments.

PMID- 7808417
TI  - A Drosophila gene encoding a DEAD box RNA helicase can suppress loss of wee1/mik1
      function in Schizosaccharomyces pombe.
AB  - We describe a screen to isolate cDNAs encoding Drosophila mitosis inhibitors
      capable of suppressing the mitotic catastrophe phenotype resulting in
      Schizosaccharomyces pombe from the combination of the wee1-50 mutation with
      either a deletion allele of mik1, or with overexpression of cdc25+. One plasmid
      was isolated which could suppress the temperature sensitive lethality of both
      these strains. The cDNA in this plasmid encodes a protein highly homologous to
      the DEAD-box family of ATP-dependent RNA helicases, rather than to protein
      kinases as might be expected. It is possible that the RNA helicase described here
      may regulate entry into mitosis by down regulating the expression of other genes
      whose activity may be rate-limiting for entry into mitosis.

PMID- 7808418
TI  - Genetic differentiation in a captive population of the endangered Siberian crane
      (Grus leucogeranus Pall.).
AB  - DNA fingerprinting, followed by multivariate analysis of data, was used to
      characterize genetic heterogeneity in captive populations of the endangered
      Siberian and sandhill cranes. The genetic structure revealed reflected the
      natural population and species distributions. The relevant groups differed not
      only from each other, but also from interspecies and inter-population hybrids
      bred in captivity. In this study we have tested an approach to the analysis of
      population structure based on individual genotypes. Interpretation of
      fingerprinting data by means of the analytical system applied here is a useful
      and reliable procedure for the estimation of genetic relationships between
      individuals.

PMID- 7808419
TI  - The human delta-opioid receptor: genomic organization, cDNA cloning, functional
      expression, and distribution in human brain.
AB  - We have used the mouse delta-opioid receptor (mDOR) cDNA to isolate the mDOR gene
      and its human homologue. In both species the coding region is interrupted by two
      introns with conserved exon-intron boundaries located after transmembrane domains
      1 and 4. Using the polymerase chain reaction and primers based on the sequence of
      the cloned human delta-opioid receptor (hDOR) gene, we have obtained a full
      length cDNA encoding the hDOR from SH-SY5Y neuroblastoma cells. The cDNA sequence
      is 100% identical to the cloned human genomic sequence and 94% identical to the
      mouse sequence at the protein level. When expressed in COS cells, hDOR displays
      nanomolar affinities for delta-selective ligands, whereas the affinities for mu-
      and kappa-selective ligands are in the micromolar range. The delta agonists [D
      Ala2, D-Leu5]enkephalin, cyclic [D-penicillamine2,D-penicillamine5]enkephalin,
      and BW373U86 efficiently decrease forskolin-induced cAMP levels in hDOR
      expressing COS cells, indicating functional coupling of the receptor. The
      distribution of hDOR mRNA in human brain was investigated using delta-selective
      reverse transcription-polymerase chain reaction amplification, followed by
      Southern hybridization with a delta-specific probe. The transcript is found in
      cortical areas, including olfactory bulb, hippocampus, and amygdala, as well as
      in basal ganglia and hypothalamus. No expression is detected in internal globus
      pallidus, thalamus, any investigated brainstem structure, or pituitary gland.
      Taken together, our results indicate similar structural, pharmacological,
      functional, and anatomical properties for the hDOR and the mDOR and therefore
      support the use of rodent models for the study of these receptors in opioid
      function.

PMID- 7808420
TI  - Purification to homogeneity of the heteromeric DNA-binding form of the aryl
      hydrocarbon receptor from rat liver.
AB  - The aryl hydrocarbon receptor (AhR) is a transcriptional enhancer that is
      activated by the binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and
      related toxic xenobiotics, as well as some naturally occurring compounds. Ligand
      binding initiates 1) dissociation of the ligand-bound monomeric AhR from the
      ligand-unoccupied multimeric complex and 2) biochemical and/or conformational
      changes that enable association of the ligand-bound monomer with other proteins.
      This heteromeric complex has high affinity for specific elements [dioxin
      responsive elements (DREs)] in the regulatory regions of a number of structural
      genes, the induction and/or repression of which may be a mechanism of toxicity of
      TCDD. We have developed a relatively simple and rapid procedure that enables
      purification to homogeneity of a TCDD-bound receptor complex. The final step of
      purification is based on binding to an oligonucleotide containing the specific
      DRE sequence that is found in the upstream region of the CYP1A1 structural gene.
      The purified complex retains in vitro DRE-binding function. Silver staining and
      Western blot analyses demonstrate that the complex consists of the AhR ligand
      binding monomer of approximately 104 kDa, plus two proteins (94 and 96 kDa) that
      are recognized by antibodies prepared against the AhR nuclear translocator
      protein. Previous attempts to purify a DRE-binding form of the AhR were
      unsuccessful because of dissociation of the complex during chromatography; this
      is the first report of an isolated functional complex. The purified preparation
      will be valuable in further studies of receptor regulation and function.

PMID- 7808421
TI  - Selective labeling and localization of the M4 (m4) muscarinic receptor subtype.
AB  - We report here a novel strategy for the selective labeling and localization of
      the M4 (m4) muscarinic receptor subtype, based on the distinct kinetics of the
      muscarinic antagonists dexetimide and N-methylscopolamine (NMS) and on the
      selectivity profile of guanylpirenzepine and AF-DX 116 for the m1-m5 muscarinic
      receptor subtypes expressed in CHO-K1 cells. Incubation with 10 nM dexetimide, a
      nonselective antagonist, resulted in > 90% occupancy of each of the m1-m5
      receptor subtypes. The relatively rapid rates of dexetimide dissociation from the
      m1, m2, and m4 receptor subtypes (t1/2 values of < 12.5 min) and the slower rates
      of dexetimide dissociation from the m3 and m5 receptor subtypes (t1/2 values of
      65 and 75 min, respectively) favored the labeling of the m1, m2, and m4 receptor
      subtypes with short incubations with [3H]NMS. Inclusion of 200 nM
      guanylpirenzepine and 250 nM AF-DX 116 prevented the binding of [3H]NMS to the
      majority of the m1 and m2 receptor subtypes, respectively, resulting in primary
      labeling of the m4 receptor subtype. Brief dissociation of the radioligand in the
      presence of 1 microM atropine improved the ratio of m4 to m2 labeling by
      selectively removing [3H]NMS from the m2 subtype. Under these conditions, the
      ratio of [3H]NMS binding to the m4 versus m1, m2, m3, and m5 receptor subtypes
      was 4:1. In vitro autoradiography combined with these m4-selective labeling
      conditions demonstrated that the M4 (m4) receptor subtype was localized to the
      primary visual area (V1, area 17, occipital cortex) and the basal ganglia, a
      distribution distinct from that demonstrated for the M1 (m1), M2 (m2), and M3
      (m3) receptor subtypes. These results demonstrate that a combination of the
      distinct kinetics of dexetimide and NMS and the receptor subtype selectivity of
      guanylpirenzepine and AF-DX 116 provides a valuable labeling strategy to examine
      the distribution and localization of the M4 (m4) muscarinic receptor subtype in
      brain, peripheral tissues, and cell lines.

PMID- 7808422
TI  - The carboxyl terminus of bovine rhodopsin is not required for G protein
      activation.
AB  - Rhodopsin, the photoreceptor of mammalian rod cells, shares regions of structural
      homology with many G protein-coupled receptors. One of these domains is the
      "fourth cytoplasmic loop" formed by palmitoylation of two cysteines (Cys-322 and
      Cys-323) in the carboxyl terminus. Evidence from several laboratories suggests
      that this domain is important for the activation of the G protein for rhodopsin,
      Gt, and that it undergoes conformational changes upon exposure to light.
      Previously we reported that a truncation mutant with only six amino acids
      remaining at the proximal end of the carboxyl terminus was able to activate Gt,
      whereas a mutant lacking an additional five amino acids was misfolded and unable
      to bind retinal. In the present report, these six amino acids were mutated, to
      define their roles in the formation of a functional photoreceptor and in the
      activation of Gt. All of the point mutants displayed normal expression, post
      translational processing, and Gt activation, suggesting that the fourth
      cytoplasmic loop in the carboxyl terminus does not play a major role in the
      activation of G proteins and that the specific amino acid sequence in this domain
      is not required for the production of a properly folded, functional
      photoreceptor.

PMID- 7808423
TI  - Correlation of activation of Ca2+/calmodulin-dependent protein kinase II with
      catecholamine secretion and tyrosine hydroxylase activation in cultured bovine
      adrenal medullary cells.
AB  - We have investigated the activation of Ca2+/calmodulin-dependent protein kinase
      II (CaM kinase II) in cultured bovine adrenal medullary cells. The activation was
      assayed as an increase in the Ca(2+)-independent (autonomous) activity of CaM
      kinase II, using the synthetic substrate Syntide-2. Incubation of cells with
      acetylcholine increased the Ca(2+)-independent activity in a time (20 sec to 5.0
      min)- and concentration (10-300 microM)-dependent manner. These curves were
      closely correlated with those of catecholamine secretion and tyrosine hydroxylase
      activation. Removal of extracellular Ca2+ completely abolished the stimulatory
      effects of acetylcholine on the Ca(2+)-independent activity, as well as on
      catecholamine secretion and activation of tyrosine hydroxylase. Nicotine but not
      muscarine increased the Ca(2+)-independent activity as potently as did
      acetylcholine, and hexamethonium but not atropine completely blocked the
      acetylcholine-induced increase. In 32P-labeled cells, acetylcholine stimulated
      the phosphorylation of a 50-kDa protein that was immunoprecipitated with an anti
      brain CaM kinase II antibody. These results suggest that acetylcholine stimulates
      CaM kinase II activity through nicotinic acetylcholine receptor-mediated influx
      of Ca2+ and that the activation of CaM kinase II is closely related to
      catecholamine secretion and tyrosine hydroxylase activation in cultured adrenal
      medullary cells.

PMID- 7808424
TI  - Chronic exposure to benzodiazepine receptor ligands uncouples the gamma
      aminobutyric acid type A receptor in WSS-1 cells.
AB  - Chronic exposure to benzodiazepines can result in an "uncoupling" of gamma
      aminobutyric acid (GABA) receptors and benzodiazepine receptors (BzR) both in
      primary neuronal cell cultures and in vivo. The effect of chronic exposure to BzR
      ligands was examined in an engineered cell line (WSS-1) stably expressing "type
      I" GABAA receptors. Chronic exposure to flurazepam produced a concentration-
      (EC50, approximately 1.1 microM after a 48-hr exposure) and time-dependent (t1/2,
      approximately 3 hr at 100 microM) reduction in the efficacy (Emax) of GABA to
      enhance [3H]flunitrazepam binding to BzR, a characteristic of uncoupling in
      native GABAA receptor isoforms. Uncoupling of GABAA receptors and BzR without
      concomitant changes in BzR density was also produced by chronic exposure to
      other, structurally diverse, BzR ligands, including Ro 15-1788 and methyl-6,7
      dimethoxy-4-ethyl-beta-carboline-3-carboxylate, but was not manifested after
      exposure to the 5-hydroxytryptamine reuptake blocker fluoxetine. Chronic (12-48
      hr) exposure to flurazepam did not remarkably alter levels of alpha 1 and gamma 2
      mRNAs, which constitute GABAA receptors in this cell line. Based on these
      findings, it is hypothesized that uncoupling of GABAA receptors and BzR in this
      engineered cell line can proceed without the elaboration of additional novel
      subunits and could involve either post-translational modification of GABAA
      receptor proteins or changes in subunit stoichiometry.

PMID- 7808425
TI  - Quantitation of mitochondrial DNA in human lymphoblasts by a competitive
      polymerase chain reaction method: application to the study of inhibitors of
      mitochondrial DNA content.
AB  - With increasing awareness of the mitochondrial toxicity associated with certain
      2',3'-dideoxynucleosides used in anti-human immunodeficiency virus therapy,
      procedures for quantitative analyses of drug effects on mitochondrial DNA (mtDNA)
      have assumed enhanced importance. For this reason we have developed a method to
      measure the copy numbers of mtDNA in cultured MOLT-4 cells. First a hybrid
      competitive DNA template was synthesized by conventional polymerase chain
      reaction (PCR), using two custom-synthesized 40-mer composite primers
      incorporating mitochondrial displacement loop sequences linked by a non
      mitochondrial cDNA template (a 76-base pair sequence from the tat/rev region of
      human immunodeficiency virus cDNA). For the competitive assay, increasing known
      copy numbers of the hybrid competitive template were added as an internal control
      to samples containing total cellular DNA. With this approach, two competitive PCR
      products were generated, 1) a mitochondrial displacement loop-derived fragment
      (182 base pairs) and 2) a competitive DNA template-derived fragment (156 base
      pairs). Absolute quantitation was achieved by radiometric comparison of the
      relative amounts of the two products. To test the versatility of this method,
      varying amounts of competitive template (6.6 x 10(4) to 6.6 x 10(9) copies) were
      used with a fixed quantity of total cellular DNA taken from cells cultured for 9
      days in the presence or absence of selected pyrimidine and purine
      dideoxynucleosides. The results showed that the copy number of cellular mtDNA is
      823 +/- 71 copies/cell in MOLT-4 cells. Little selective depletion of mtDNA,
      compared with total cellular DNA, was seen with the purine dideoxynucleosides
      examined; however, when the cells were exposed to the pyrimidine
      dideoxynucleoside 2',3'-dideoxycytidine (50 nM) for 9 days, mtDNA content was
      specifically depleted, although total cellular DNA decreased by only 10%. Thus,
      in addition to the presently used methods of assessing mitochondrial impairment,
      i.e., Southern blot analysis and electron microscopy, the competitive PCR method
      provides a third and convenient assay, with particular applicability to
      determination of mtDNA in very small numbers of cells.

PMID- 7808426
TI  - Evidence for a common mechanism of action for fatty acids and thiazolidinedione
      antidiabetic agents on gene expression in preadipose cells.
AB  - In diabetic rodents, thiazolidinediones are able to improve insulin sensitivity
      of target tissues and to reverse, at least partially, the diabetic state. The
      effects of these drugs on phenotypic expression in various tissues, including
      adipose tissue, have been reported. We report here that a new thiazolidinedione
      compound, BRL 49653, exerts, in preadipose cells, potent effects on the
      expression of genes encoding proteins involved in fatty acid metabolism. These
      effects of BRL 49653 in Ob 1771 preadipose cells are similar, in terms of
      kinetics, reversibility, specificity of genes affected, and requirement for
      protein synthesis, to those already described for natural or nonmetabolizable
      fatty acids. Moreover, when used at submaximally effective concentrations,
      BRL49653 and 2-bromopalmitate act in an additive manner to induce gene expression
      in preadipose cells, but this additivity of effects is lost when one of the
      compounds is used at a maximally effective concentration. These observations,
      suggesting similar mechanisms of action for thiazolidinediones and fatty acids,
      are strongly supported by the demonstration that (i) both molecules activate, in
      a heterogolous trans-activation assay, the same nuclear receptor of the
      steroid/thyroid hormone nuclear receptor superfamily and (ii) transfection of 3T3
      C2 fibroblasts with an expression vector for this nuclear receptor confers
      thiazolidinedione inducibility of adipocyte lipid-binding protein gene
      expression.

PMID- 7808427
TI  - Interleukin-1-induced intracellular signaling pathways converge in the activation
      of mitogen-activated protein kinase and mitogen-activated protein kinase
      activated protein kinase 2 and the subsequent phosphorylation of the 27
      kilodalton heat shock protein in monocytic cells.
AB  - Interleukin (IL)-1 plays a central role in human host defense. Binding of IL-1 to
      its receptor is associated with phosphorylation of various cellular target
      proteins, most of which are unidentified. The kinases responsible for target
      protein phosphorylation after IL-1 stimulation are also still not completely
      understood. We report here that IL-1 induced activation of mitogen-activated
      protein (MAP) kinase in primary monocytes and in the human monocytic leukemia
      cell line U-937. Activation of MAP kinase was followed by activation of MAP
      kinase-activated protein (MAPKAP) kinase 2, a serine/threonine kinase, leading to
      subsequent phosphorylation of the small heat shock protein [27-kDa heat shock
      protein (Hsp27)]. Phosphorylation of Hsp27 triggered by IL-1 was both dose and
      time dependent. IL-1 failed to phosphorylate Hsp27 when cells had been previously
      deactivated with tyrosine kinase inhibitors such as genistein. In those cells,
      however, Hsp27 phosphorylation could be reconstituted when activated
      immunoprecipitated MAP kinase or purified MAPKAP kinase 2 was added.
      Phosphorylation of Hsp27 could also be inhibited when NaF, a serine/threonine
      phosphatase inhibitor, was omitted. Taken together, our findings indicate that IL
      1-induced intracellular signaling pathways converge in the activation of MAP
      kinase and MAPKAP kinase 2 and the subsequent phosphorylation of Hsp27.

PMID- 7808428
TI  - Paradoxical derepression of collagenase gene expression by the antirheumatic gold
      compound aurothiomalate.
AB  - The neutral metalloproteinase collagenase is known to be, among others, one of
      the key enzymes promoting joint destruction in patients with rheumatoid
      arthritis. Because inflammatory cytokines, e.g., interleukin-1 and tumor necrosis
      factor-alpha, are considered to activate collagenase gene expression through
      activation of the transcription factor activator protein-1, we examined whether
      the water-soluble gold compound aurothiomalate (AuTM) influenced collagenase gene
      expression, using phorbol ester-treated human fibroblasts. However, AuTM did not
      prevent phorbol ester-mediated activation of activator protein-1 DNA-binding
      activity and subsequent induction of collagenase gene expression. In contrast,
      AuTM counteracted the repressive effects of glucocorticoids on collagenase gene
      expression and restored collagenase mRNA levels. The molecular target of this
      paradoxical AuTM action was suggested to be the glucocorticoid receptor.

PMID- 7808430
TI  - Transforming growth factor-beta 1 down-regulates basal and polycyclic aromatic
      hydrocarbon-induced cytochromes P-450 1A1 and 1A2 in adult human hepatocytes in
      primary culture.
AB  - The effects of interleukin (IL)-1 beta, IL-4, IL-6, tumor necrosis factor (TNF)
      alpha, interferon (IFN)-alpha, IFN-gamma, and transforming growth factor (TGF)
      beta 1 on cytochrome P-450 (CYP) 1A expression and polycyclic aromatic
      hydrocarbon (PAH)-mediated induction in primary human hepatocyte cultures were
      determined. Most cytokines that were previously found to decrease basal CYP
      expression could counteract PAH induction of CYP1A mRNA and its associated
      ethoxyresorufin-O-deethylation (EROD) activity. IL-1 beta and TNF-alpha blocked 3
      methylcholanthrene (3-MC)-induced EROD activity by up to 25 and 44%,
      respectively. IFN-alpha and IFN-gamma antagonized EROD induction by up to 61 and
      70%, respectively. TGF-beta 1 proved to be the most effective cytokine, because
      72 hr of treatment with 2 ng/ml TGF-beta 1 produced nearly 100% inhibition of 3
      MC- and benzo(a)pyrene-induced CYP1A1 and CYP1A2 mRNAs and EROD activity.
      Treatment with cycloheximide in combination with 3-MC led to superinduction of
      CYP1A mRNA, under which conditions TGF-beta 1 did not block induction, suggesting
      the requirement for protein synthesis for the suppressive effect of the cytokine.
      In addition, TGF-beta 1 augmented AP-1-binding activity, suggesting that fos
      and/or jun protooncogene products could be implicated in the response. Our
      results demonstrate that IL-1 beta, TNF-alpha, and IFNs antagonized PAH-mediated
      induction of CYP1A gene expression in human hepatocytes. In addition, we report
      the finding of a novel effect of TGF-beta 1, which was able to prevent CYP1A1 and
      -1A2 induction by two different PAHs.

PMID- 7808429
TI  - Catalytic selectivity and mechanism-based inactivation of stably expressed and
      hepatic cytochromes P450 2B4 and 2B5: implications of the cytochrome P450 2B5
      polymorphism.
AB  - Cytochrome P450 (P450) 2B5 was recently found to be functionally distinct from
      three other rabbit P450 2B forms, based on androstenedione hydroxylase
      activities. In this investigation, we examined the frequency of the P450 2B5-null
      phenotype and the functional consequences of polymorphic P450 2B5 expression in
      hepatic microsomes from phenobarbital-treated rabbits. Four of the 10 animals
      examined did not have detectable levels of P450 2B5 mRNA and exhibited much lower
      microsomal androstenedione 15 alpha- and 16 alpha-hydroxylase activities. The 15
      alpha-hydroxylase activity was found to correlate (r = 0.91) with liver P450 2B5
      mRNA. P450 2B4 and 2B5 were stably expressed in human kidney 293 cells to further
      characterize substrate specificities and to investigate mechanism-based
      inactivation by phencyclidine. P450 2B4 was 4-16-fold more active than 2B5
      towards benzphetamine, 7-ethoxycoumarin, methylenedioxybenzene, and
      pentoxyresorufin. Benzyloxyresorufin O-debenzylase activity was 160-fold higher
      for P450 2B4 than P450 2B5. Anti-P450 2B4 IgG inhibited benzyloxyresorufin O
      debenzylation nearly completely in untreated and phenobarbital-induced liver
      microsomes. Phencyclidine selectively inactivated P450 2B4, compared with 2B5, in
      both human kidney 293 cell and liver microsomes. Poor inactivation of P450 2B5 by
      phencyclidine was found to be a result of its low maximal rate constant. Results
      of this study establish the idea that the metabolic consequences of phenobarbital
      induction depend on the potential of animals to express functionally variant P450
      2B forms. Furthermore, we conclude that one or more of the 11 amino acid
      differences between these highly related P450 forms are critical to their
      substrate specificities and selective inactivation.

PMID- 7808433
TI  - Atypical low density lipoprotein binding site that may mediate lipoprotein
      induced signal transduction.
AB  - The characteristics of low density lipoprotein (LDL) binding in quiescent
      cultures of human vascular smooth muscle cells (VSMC) have been further
      investigated and compared with the characteristics of high affinity LDL binding
      in human fibroblasts [via the apolipoprotein (apo) B/E receptor] and with the
      properties of LDL-induced phosphoinositide catabolism in VSMC. In VSMC the bulk
      of specific 125I-LDL binding occurs at a low affinity site, several
      characteristics of which are distinct from those of 125I-LDL binding to the apo
      B/E receptor in fibroblasts. (a) The affinity of LDL binding in VSMC is 25-50
      times lower than that in fibroblasts (Kd approximately 50 micrograms/ml versus Kd
      approximately 2 micrograms/ml). (b) The kinetics of LDL association and
      dissociation in VSMC are more rapid than those in fibroblasts. (c) In contrast to
      apo B/E receptor-mediated binding of LDL in fibroblasts, binding of LDL to VSMC
      is insensitive to heparin, chemical modification of lysine residues, and
      chelation (with EDTA) of divalent cations. (d) Apo E-free high density
      lipoprotein 3 displaces labeled LDL more effectively in VSMC than in fibroblasts.
      (e) The ratio of bound/internalized LDL to degraded LDL differs markedly between
      fibroblasts and VSMC. LDL-stimulated phosphoinositide catabolism in VSMC, which
      occurs with an activation constant similar to the Kd for low affinity LDL
      binding, is insensitive to heparin, modification of lysine and arginine residues
      in LDL, and chelation of divalent cations. Thus, the atypical low affinity
      receptor in these cells may mediate the effects of LDL on signal transduction.

PMID- 7808431
TI  - Comparative recovery kinetics of 5-hydroxytryptamine 1A, 1B, and 2A receptor
      subtypes in rat cortex after receptor inactivation: evidence for differences in
      receptor production and degradation.
AB  - The present study investigates the comparative repopulation kinetics of 5
      hydroxytryptamine (5-HT)1A, 5-HT1B, and 5-HT2A receptors in rat cortex
      homogenates after irreversible receptor inactivation by N-ethoxycarbonyl-1,2
      ethoxydihydroquinoline. Adult male rats were administered a single subcutaneous
      dose of vehicle (1:1 ethanol/water) or N-ethoxycarbonyl-1,2
      ethoxydihydroquinoline (10 mg/kg), and the recovery of 5-HT receptor subtypes was
      measured at various times after injection (4-336 hr). Despite comparable control
      Bmax values for 5-HT1A (84 +/- 2 fmol/mg of protein) and 5-HT1B (94 +/- 4
      fmol/mg) subtypes, marked differences were noted in their 1) receptor production
      rates (r = 0.349 versus 0.235 fmol/mg of protein/hr), 2) receptor degradation
      rate constants (k = 0.0056 versus 0.0033 hr-1), and 3) half-lives of receptor
      recovery (124.1 versus 212.5 hr). For 5-HT2A receptors, both r and k for agonist
      [(+/-)-1-(2,5-dimethoxy-4-[125I]iodophenyl)-2-aminopropane]- or antagonist
      ([3H]ketanserin)-labeled sites were markedly greater than the respective values
      for the 5-HT1 subtypes. In addition, the significantly different Bmax values for
      agonist- versus antagonist-labeled 5-HT2A receptors (79 +/- 4 versus 206 +/- 10
      fmol/mg) were reflected exclusively as a 2.6-fold difference in receptor
      production rates, because degradation rate constants (k) were identical.
      Moreover, the stoichiometry of agonist-labeled to antagonist-labeled 5-HT2A
      receptors was not altered at any time point during recovery. These data indicate
      that 1) comparable receptor steady state Bmax values for 5-HT receptor subtypes
      may be due to markedly different receptor kinetic parameters (r and k), 2)
      differences in r and k are greater between 5-HT receptor families (i.e., 5-HT1
      versus 5-HT2) than among subtypes within a family (i.e., 5-HT1A versus 5-HT1B),
      and, 3) despite marked changes in 5-HT2A receptor density, the percentage of
      receptors in the agonist-labeled, high affinity state is maintained.

PMID- 7808432
TI  - Ca2+ permeability of cloned and native 5-hydroxytryptamine type 3 receptors.
AB  - We have used single-cell imaging of fura-2-loaded cells to examine the Ca2+
      signals evoked by activation of 5-hydroxytryptamine type 3 (5-HT3) receptors in
      undifferentiated N1E-115 neuroblastoma cells and in human embryonic kidney (HEK)
      293 cells transfected with either of the two cloned 5-HT3 receptor subunits. The
      selective 5-HT3 receptor agonist 1-(m-chlorophenyl)-biguanide (mCPBG) caused a
      concentration-dependent increase in the cytoplasmic Ca2+ concentration ([Ca2+]i)
      in N1E-115 cells and in HEK 293 cells transfected with either the 5-HT3 A subunit
      or the 5-HT3 As subunit. In each case, the [Ca2+]i rise was steeply dependent on
      the mCPBG concentration (nH = 2-4) and abolished by removal of extracellular Ca2+
      or addition of ondansetron. Pretreatment of N1E-115 cells with thapsigargin,
      caffeine, and ryanodine to deplete intracellular Ca2+ stores had no effect on the
      mCPBG-evoked Ca2+ signals, indicating that they result entirely from stimulated
      Ca2+ entry. The steep concentration-effect curves therefore are not a consequence
      of amplification of Ca2+ influx by Ca(2+)-induced Ca2+ release from intracellular
      stores and probably reflect cooperative activation of 5-HT3 receptors by mCPBG.
      Depolarization of transfected HEK 293 cells with medium containing increased K+
      concentrations invariably failed to evoke an increase in [Ca2+]i, confirming the
      absence of voltage-gated Ca2+ channels and indicating that the mCPBG-evoked rise
      in [Ca2+]i results from Ca2+ permeation of 5-HT3 receptors. However, in N1E-115
      cells and transfected HEK 293 cells, both extracellular Na+ and K+ substantially
      inhibited the Ca2+ influx evoked by activation of 5-HT3 receptors, possibly by
      inhibition of agonist binding or by competition with Ca2+ for permeation of the
      channel. We conclude that 5-HT3 receptors are Ca2+ permeant, that the Ca2+ influx
      is sufficient to generate a significant rise in [Ca2+]i, and that, because the A
      and As subunits behave similarly, conflicting electrophysiological analyses of
      Ca2+ currents cannot be explained by differences between these two subunits.

PMID- 7808434
TI  - Disruption by lithium of phosphatidylinositol-4,5-bisphosphate supply and
      inositol-1,4,5-trisphosphate generation in Chinese hamster ovary cells expressing
      human recombinant m1 muscarinic receptors.
AB  - Inhibitory effects of the anti-manic agent lithium on carbachol-stimulated
      phosphoinositide signaling have been investigated in Chinese hamster ovary (CHO)
      cells transfected with human m1 muscarinic receptor cDNA (Bmax, 816 fmol/mg of
      protein). In the presence of Li+, a time-dependent inhibition of inositol-1,4,5
      trisphosphate [Ins(1,4,5)P3] mass accumulation was observed within 10 min of
      agonist addition (IC50 for lithium inhibition at 20 min after carbachol addition,
      0.5 mM). The Li(+)-induced decrease in agonist-stimulated Ins(1,4,5)P3 levels was
      preceded by a dramatic increase in CMP-phosphatidate accumulation. The idea that
      Li+ blockade of inositol monophosphatase caused a rapid depletion of the cellular
      myo-inositol pool in CHO-m1 cells was supported by the reversal of Li+ effects by
      exogenous myo-inositol. Carbachol (1 mM) alone caused a rapid and dramatic
      decrease in phosphatidylinositol-4,5-bisphosphate [PtdIns(4,5)-P2]in CHO-m1 cells
      labeled to equilibrium with [3H]-inositol. Carbachol-evoked decreases in
      PtdIns(4,5)P2 were time-dependently accentuated by Li+ (IC50 for Li+ inhibition
      at 20 min after carbachol addition, 1.2 mM). Measurements of changes in
      PtdIns(4,5)P2 mass demonstrated that the effect of Li+ was completely and
      concentration-dependently reversed by addition of myo-inositol. Sequential 30-min
      periods of carbachol stimulation resulted in similar time courses of Ins(1,4,5)P3
      accumulation when an intervening 20-min recovery period was included in the
      protocol. Inclusion of Li+ throughout resulted in a more rapid and dramatic
      attenuation of Ins(1,4,5)P3 during the agonist rechallenge period, which could be
      correlated with accentuated changes in PtdIns(4,5)P2. These data demonstrate
      that, although mechanisms operate to efficiently resynthesize PtdIns(4,5)P2, the
      temporal correlation of carbachol-evoked decreases in PtdIns(4,5)P2 levels in the
      presence of Li+ strongly suggests that phosphoinositide-specific phospholipase C
      substrate depletion may be causal in the subsequent decrease in Ins(1,4,5)P3
      levels.

PMID- 7808435
TI  - Gating properties of mutant acetylcholine receptors.
AB  - A number of affinity labeling studies have identified several tyrosine residues
      in the alpha subunit of the nicotinic acetylcholine receptor as being in or near
      the ligand binding site. Studies employing site-directed mutagenesis of these
      residues (alpha Y93, alpha Y190, and alpha Y198; the notation used is
      subunit/amino acid/position in the Torpedo receptor/substitution) in mouse
      muscle, Torpedo electroplax, and alpha 7 neuronal acetylcholine receptors have
      demonstrated that substitution of phenylalanine for tyrosine results in a shift
      towards higher concentrations in the macroscopic dose-response curves for
      acetylcholine-elicited currents from voltage-clamped Xenopus oocytes that express
      the receptors. This decrease in apparent affinity has been ascribed to either a
      reduction in binding affinity or a reduction in the coupling of agonist binding
      to ion channel opening; both mechanisms would give rise to shifts in the dose
      response curves. We have used kinetic analysis of ion channel gating at the
      single-channel level to obtain estimates for the rate constants associated with
      the ligand binding and channel opening steps for wild-type, alpha Y93F, and alpha
      Y198F receptors. The results suggest that the underlying cause of the shifts in
      the macroscopic dose-response curves is a reduction in acetylcholine affinity for
      the resting activatable state of the receptor. Furthermore, it is the association
      rate for agonist binding, rather than the dissociation rate, that is most
      affected by the mutations.

PMID- 7808436
TI  - Biphasic modulation of the strychnine-sensitive glycine receptor by Zn2+.
AB  - The effects of extracellular applications of Zn2+ ions on the strychnine
      sensitive glycine receptor were studied in cultured rat spinal cord neurons and
      with recombinant glycine receptors expressed in human embryonic kidney 293 cells.
      Nanomolar concentrations of Zn2+ enhanced the chloride ion current in response to
      brief applications of 100 microM glycine. The enhancement of glycine responses
      increased from 20 nM to 1 microM Zn2+. Higher concentrations of Zn2+ caused a
      reversal of the potentiation, followed by progressive inhibition of the glycine
      response up to approximately 20-50 microM Zn2+. The biphasic modulation by Zn2+
      appeared essentially identical in native and recombinant glycine receptors.
      Biphasic Zn2+ modulation was observed both with picrotoxin-insensitive
      heteromeric (alpha 2/beta) receptors and with picrotoxin-sensitive homomeric
      receptors consisting only of alpha 2 subunits. This suggests that the alpha
      subunit alone is sufficient for formation of two distinct Zn2+ binding sites on
      the glycine receptor. The demonstration of Zn2+ modulation of the strychnine
      sensitive glycine receptor is of potential physiological importance, in view of
      the likely range of subsynaptic Zn2+ concentrations to which the receptor is
      exposed.

PMID- 7808437
TI  - Site-directed mutagenesis of the peripheral benzodiazepine receptor:
      identification of amino acids implicated in the binding site of Ro5-4864.
AB  - The peripheral benzodiazepine receptor (PBR) is an 18-kDa protein present in the
      outer mitochondrial membrane. The human PBR can be labeled with the
      benzodiazepine Ro5-4864 and with the isoquinoline carboxamide PK11195. The two
      ligands compete with each other in binding experiments, with previous results
      suggesting overlapping but not identical binding sites. To define the regions of
      the receptor interacting with PK11195 and Ro5-4864 and to address the question of
      the topology of the molecule in the membrane, we generated mutant human PBRs with
      amino- and carboxyl-terminal deletions and with point mutations in potentially
      accessible cytoplasmic regions. The mutant genes were expressed in yeast and
      analyzed in binding experiments using radiolabeled PK11195 and Ro5-4864. The
      results showed that, whereas deletions in the amino-terminal sequence had marked
      consequences for the binding affinity of both ligands, the final 13 amino acids
      at the carboxyl terminus could be deleted with no effect on the binding of either
      Ro5-4864 or PK11195. The site-directed mutagenesis experiments pinpointed four
      amino acids as participating in the binding site of Ro5-4864. Three of these, Glu
      29, Arg-32, and Lys-39, which are located in the first putative cytoplasmic loop,
      are conserved in human, bovine, rat, and mouse PBRs. The remaining residue, Val
      154, which is found at the interface between the putative fifth transmembrane
      region and the cytoplasm, is present in the human, rat, and mouse sequences but
      is replaced by methionine in the bovine sequence. The exchange of Met-154 for
      valine in the bovine PBR introduced a binding site for Ro5-4864, which is absent
      in the native PBR. These four amino acids played a minor role, if any, in the
      binding site of PK11195. We also showed that the histidines previously suggested
      to be part of the binding site of PK11195 are not directly involved in the
      interaction of the human receptor with either PK11195 or Ro5-4864.

PMID- 7808438
TI  - Unusual pharmacology of (+)-tubocurarine with rat neuronal nicotinic
      acetylcholine receptors containing beta 4 subunits.
AB  - We have investigated the functional properties of four rat neuronal nicotinic
      acetylcholine receptor types expressed in Xenopus oocytes after injection of
      pairwise combinations of mRNA encoding alpha 2 or alpha 3 receptor subunits with
      mRNA encoding beta 2 or beta 4 receptor subunits. Current responses evoked by
      rapid application of cholinergic agonists (acetylcholine, nicotine, or 1,1
      dimethyl-4-phenylpiperazinium) were recorded from voltage-clamped oocytes.
      Substituting BaCl2 for CaCl2 in the external solution increased the apparent Kd
      values of beta 4 subunit-containing receptors for acetylcholine but decreased the
      apparent Kd values of beta 2 subunit-containing receptors. Inhibition curves for
      the cholinergic antagonist (+)-tubocurarine were measured in BaCl2 medium at low
      agonist concentrations. (+)-Tubocurarine was a competitive antagonist of
      acetylcholine at neuronal nicotinic acetylcholine receptors that coexpressed the
      beta 2 subunit; the estimated Kb values were 3.6 microM (alpha 2 beta 2
      receptors) and 390 nM (alpha 3 beta 2 receptors). In contrast, (+)-tubocurarine
      enhanced the peak responses evoked by low acetylcholine concentrations at alpha 2
      beta 4 and alpha 3 beta 4 neuronal nicotinic acetylcholine receptors, without
      being a partial agonist. The maximal increase was observed at 5 microM and 10
      microM (+)-tubocurarine for alpha 2 beta 4 and alpha 3 beta 4 receptors,
      respectively. Higher (+)-tubocurarine concentrations inhibited cholinergic
      responses, thus yielding a "bell-shaped" concentration-response curve.

PMID- 7808439
TI  - 4-Aminopyridine binding and slow inactivation are mutually exclusive in rat Kv1.1
      and Shaker potassium channels.
AB  - In the present study we have used two-electrode voltage-clamping of Xenopus
      oocytes expressing either Kv1.1 or Shaker B (ShB) delta 6-46 K+ channels to
      examine the effects of 4-aminopyridine (4-AP) on the process of slow
      inactivation. Neither of these channels exhibits fast inactivation. Channel
      activation was required for block by 4-AP in both channel types. In the absence
      of drug, inactivation of Kv1.1 and ShB delta 6-46 channels at 0 mV was
      biexponential [tau fast = 7.8 +/- 0.3 sec, tau slow = 33.9 +/- 0.9 sec, and
      Aslow/(Afast + Aslow) = 0.79 +/- 0.02 (n = 10) for Kv1.1 and tau fast = 3.5 +/-
      0.4 sec, tau slow = 13.1 +/- 1.8 sec, and Aslow/(Afast + Aslow) = 0.35 +/- 0.06
      (n = 3) for ShB delta 6-46]. In the presence of 4-AP, the rates of inactivation
      of Kv1.1 and ShB delta 6-46 were markedly slowed, resulting in a crossover
      phenomenon where, in the presence of drug, the outward current was smaller than
      control at the beginning of the depolarizing pulse but crossed over during the
      pulse to become larger than the control. The most obvious change induced by 0.2
      mM 4-AP was a 2-fold slowing of the slow phase of inactivation [tau fast = 3.9 +/
      1.1 sec, tau slow = 67.1 +/- 3.6 sec, and Aslow/(Afast + Aslow) = 0.85 +/- 0.04
      (n = 4) for Kv1.1 and tau fast = 3.5 +/- 0.4 sec, tau slow = 23.7 +/- 2.6 sec,
      and Aslow/(Afast + Aslow) = 0.75 +/- 0.02 (n = 3) for ShB delta 6-46, in the
      presence of 0.2 mM 4-AP]. In addition, there was a significant increase in the
      contribution of the slower phase of inactivation of ShB delta 6-46 channels in
      the presence of 4-AP. The slowed inactivation in the presence of 4-AP was
      accompanied by removal of 4-AP block. These results are consistent with the
      processes of 4-AP block and slow inactivation of Kv1.1 and ShB delta 6-46
      channels being mutually exclusive.

PMID- 7808440
TI  - Differential effects of melanocortin peptides on neural melanocortin receptors.
AB  - Melanocortins (MCs) have various physiological actions on the brain. The recent
      cloning of neural MC receptors opened new avenues to study the effects of these
      neuropeptides on the nervous system. Here we investigated the structure-activity
      relationships (SARs) of peptides derived from adrenocorticotropic hormone (ACTH)
      with cloned MC3 and MC4 receptors in vitro and correlated these with central
      effects of MCs in vivo. Analysis of the effects of various MC peptides on cAMP
      accumulation in and binding to cells that expressed either the rat MC3 receptor
      or the human MC4 receptor demonstrated that ACTH-4-9-NH2 was the core sequence of
      ACTH able to activate these receptors. Furthermore, gamma-melanocyte-stimulating
      hormone (MSH) displayed selectivity for the MC3 receptor, whereas [D-Phe7]ACTH-4
      10 more efficiently activated the MC4 receptor than the MC3 receptor. The
      activities of MC fragments that lacked the three carboxyl-terminal amino acids
      (residues 11-13) of ACTH-1-13 were much lower than that of alpha-MSH, for both
      receptors. Furthermore, the three amino-terminal amino acids (residues 1-3) of
      alpha-MSH were more important for full activation of the MC4 receptor, compared
      with the MC3 receptor. The SAR for the MC4 receptor resembled that for the
      induction of excessive grooming behavior by MC peptides. Therefore, we suggest
      that this behavioral response is mediated by MC4 receptors. The SAR for the MC3
      receptor did not overlap with that for in vivo effects of MCs. ORG2766, an ACTH-4
      9 analog that is very potent in an active avoidance task, did not activate,
      antagonize, or bind to the MC3 and MC4 receptors. This suggests the presence of
      still other MC receptors, in addition to the MC3 and MC4 receptors, in the brain.
      These data identify peptides with selectivity for either the MC3 receptor or the
      MC4 receptor, which may be used for development of novel MC receptor-specific
      ligands. Furthermore, this is the first report that discusses behavioral effects
      of MCs in light of data on cloned MC receptors.

PMID- 7808441
TI  - Kinetic study of the interactions between the glutamate and glycine recognition
      sites on the N-methyl-D-aspartic acid receptor complex.
AB  - The N-methyl-D-aspartate (NMDA) receptor is unique among the ligand-gated ion
      channels, in that the gating process requires the binding of two independent
      coagonists, glutamate and glycine. Receptor binding experiments have suggested
      that the coagonist recognition sites interact with one another in an allosteric
      manner, and previous work in this laboratory has provided additional functional
      support in favor of an allosteric coupling; the affinity of glutamate for its
      recognition site was reduced when a partial agonist, (+)-HA-966, occupied the
      glycine site, compared with the affinity when glycine itself was bound to the
      receptor. The present experiments have taken these observations a step further
      and compare the effects of several glycine site ligands with different affinities
      and intrinsic activities (determined from equilibrium concentration-response
      curves) on glutamate off-rate. Thus, the dissociation rate for the decay of
      glutamate-activated membrane currents in voltage-clamped rat cortical neurons was
      fastest (160 +/- 28 msec) in the presence of saturating concentrations of (+)-HA
      966 and progressively slower in the presence of D-cycloserine (258 +/- 27 msec),
      aminocyclopropanecarboxylic acid (330 +/- 21 msec), L-alanine (375 +/- 28 msec),
      and glycine (502 +/- 42 msec). We have also measured the affinities and intrinsic
      activities of several NMDA receptor ligands and report that a reciprocal
      interaction exists, such that the off-rate of glycine is influenced by the
      properties of the agonist occupying the glutamate coagonist site. Thus, the time
      constant for current decay after a brief exposure to glycine was fastest in the
      presence of a saturating concentration of cis-2,3-piperidinedicarboxylic acid
      (449 +/- 26 msec) and progressively slower in the presence of quinolinate (689 +/
      73 msec), NMDA (721 +/- 36 msec), and L-glutamate (1260 +/- 36 msec). The data
      suggested that the extent of the modulation of one site by the other is related
      to the intrinsic activity of the agonist, rather than its affinity. Specifically,
      we suggest that a partial agonist occupying one of the agonist recognition sites
      produces a conformational change that results in an accelerated off-rate for
      coagonist dissociation from the receptor; the lower the intrinsic activity, the
      greater is the effect on coagonist off-rate.

PMID- 7808442
TI  - gamma-Aminobutyric acid type A receptor antagonists picrotoxin and bicuculline
      alter acetylcholine channel kinetics in cultured embryonic rat skeletal muscle.
AB  - The effects of the classical gamma-aminobutyric acid type A receptor antagonists
      picrotoxin and bicuculline on nicotinic acetylcholine receptors in cultured
      embryonic rat skeletal muscle were examined with whole-cell and cell-attached
      single-channel recording methods. Up to 600 microM picrotoxin had little or no
      effect on the amplitude of the whole-cell current, whereas bicuculline dose
      dependently blocked it, with an IC50 value of 101.2 +/- 8.9 microM. Bicuculline
      reduced the maximum inducible acetylcholine current without changing the Kd
      value, suggesting that bicuculline uncompetitively blocked the binding of
      acetylcholine to its receptor. The elementary nicotinic acetylcholine receptor
      currents recorded in the cell-attached single-channel recording configuration
      exhibited properties typical of those recorded in embryonic muscle (approximately
      36 pS and approximately 6 msec). Picrotoxin dramatically transformed individual
      channel openings into briefly interrupted bursts, so that the number of openings
      increased while the mean open time markedly decreased. Bicuculline decreased mean
      open time to a lesser but statistically significant degree. The dominant
      component of the closed time histogram in control recordings occurred at 17 msec,
      whereas that recorded with picrotoxin occurred at 0.5 msec. Bicuculline prolonged
      the closed time, with a dominant closed time component at 52 msec. Elementary
      conductance was not altered by either agent. In conclusion, we found that the
      gamma-aminobutyric acid type A channel antagonists picrotoxin and bicuculline
      were also blockers of embryonic nicotinic acetylcholine receptor channels in
      cultured rat muscle.

PMID- 7808443
TI  - Toxicity, metabolism, DNA incorporation with lack of repair, and lactate
      production for 1-(2'-fluoro-2'-deoxy-beta-D-arabinofuranosyl)-5-iodouracil in U
      937 and MOLT-4 cells.
AB  - Two cell lines, U-937 and MOLT-4, were used to investigate the toxicity, DNA
      incorporation, and effect on mitochondria of 1-(2'-fluoro-2'-deoxy-beta-D
      arabinofuranosyl)-5-iodouracil (FIAU) and its putative metabolite 1-(2'-fluoro-2'
      deoxy-beta-D-arabinofuranosyl)-uracil (FAU). After 72-hr incubation, the IC50
      values for FIAU were 6.4 microM for U-937 cells and 26 microM for MOLT-4 cells.
      IC50 values for FAU were 10-fold higher in both cell lines. Incubation for 24 hr
      with 10 microM [2-14C]FIAU led to 2.1% and 0.93% replacement of thymidine in DNA
      of U-937 and MOLT-4 cells, respectively. The predominant radioactive species
      measurable in DNA was FIAU. A similar incubation with [2-14C]FAU resulted in 4
      fold lower DNA incorporation of a single radioactive species that coeluted with 1
      (2'-fluoro-2'-deoxy-beta-D-arabinofuranosyl)-5-methyluracil (FMAU). There was no
      evidence of a selective repair process after DNA incorporation of FIAU or FAU
      (FMAU). Increased intracellular concentrations of FIAU triphosphate and
      incorporation into DNA were associated with an increase in cellular toxicity.
      Continuous exposure to a clinically achievable concentration of FIAU, 0.44
      microM, produced a constant DNA incorporation of 0.80% and 0.11% for U-937 and
      MOLT-4 cells, respectively. FIAU was not readily metabolized to FAU or iodouracil
      by human liver in vitro. Compared with 2',3'-dideoxycytidine as a positive
      control, after 12 days of continuous exposure of U-937 and MOLT-4 cells to FIAU
      there was no evidence of increased lactate production. These data negate several
      possible mechanisms (DNA chain termination, DNA polymerase inhibition, one form
      of selective mitochondrial poisoning, and FAU-mediated toxicity) and provide
      clues for possible mechanisms (FIAU triphosphate concentration and DNA
      incorporation). Further work is needed to develop a complete explanation for the
      delayed hepatic toxicity observed in the investigational clinical trials of FIAU.

PMID- 7808444
TI  - Thallium mediates a rapid chloride/hydroxyl ion exchange through myelin lipid
      bilayers.
AB  - We have investigated the effects of several heavy metal cations on the proton and
      chloride permeabilities of liposomes prepared with endogenous lipids from brain
      myelin, by monitoring the fluorescence emitted by acridine orange and N-(6
      methoxyquinolyl)acetoethyl ester. In addition to Hg2+ and Cu+, nanomolar
      concentrations of Tl3+, but not Tl+, were able to generate a pH gradient
      (internally acidic) when an inwardly directed chloride gradient was established.
      No effect was observed either in the absence of Tl3+ or when Tl3+ was added (a)
      in the presence of chelating agents, reducing chemicals, or thiol compounds, (b)
      with identical intra- and extravesicular chloride concentrations, or (c) in the
      absence of chloride. Furthermore, Tl3+ was able to dissipate a pH gradient across
      the membrane for identical intra- and extravesicular chloride concentrations and
      to increase the chloride permeability in response to a pH gradient. All of these
      results suggest that Tl3+ behaves as a Cl-/OH- exchanger ionophore. Because the
      kinetics of the process did not vary with alterations of the membrane potential
      of the liposomes, it was concluded that the reaction is electroneutral, with a Cl
      /OH- stoichiometry of 1:1. The results presented could explain some of the
      toxicological effects, largely unknown to date, of this extremely neurotoxic
      heavy metal and raise the possibility that thallium could have one of its main
      neurotoxicological targets in myelin.

PMID- 7808445
TI  - Glutathione- and glutathione-S-transferase-dependent oxidative desulfuration of
      the thione xenobiotic diethyldithiocarbamate methyl ester.
AB  - Oxidative desulfuration of diethyldithiocarbamate methyl ester (DDTC-Me), a
      thione xenobiotic and a metabolite of disulfiram, was studied. Using a rat liver
      microsomal incubation system, DDTC-Me was oxidized at the thionosulfur group,
      forming DDTC-Me sulfine. Only minimal desulfuration of DDTC-Me to S-methyl-N,N
      diethylthiolcarbamate (DETC-Me) occurred. Desulfuration of DDTC-Me increased 4
      fold when the microsomal incubation was supplemented with reduced glutathione
      (GSH) and increased 8-fold when both GSH and glutathione-S-transferase (EC
      2.5.1.18) were added. Similar results were obtained using a simplified system
      containing DDTC-Me sulfine, GSH, and glutathione-S-transferase. This suggested
      that DDTC-Me sulfine is a stable intermediate formed before DDTC-Me is
      desulfurated to DETC-Me. This unprecedented desulfuration process can be
      explained as follows. GSH attacks the oxithiirane isomer of DDTC-Me sulfine,
      resulting in ring opening followed by loss of glutathione hydrodisulfide, which
      is reduced by GSH to oxidized glutathione and H2S. GSH can also reduce DDTC-Me
      sulfine to DDTC-Me. This mechanism is supported by in vitro studies. An
      approximately 1:1 stoichiometry was observed for the formation of H2S and DETC
      Me. A 1:1 stoichiometry was also observed for the consumption of DDTC-Me sulfine,
      formation of DETC-Me plus DDTC-Me, and formation of oxidized glutathione.
      Glutathione hydrodisulfide was trapped by derivatization in situ using 4
      vinylpyridine. Oxidative desulfuration of a series of dithiocarbamate esters also
      followed a similar mechanism.

PMID- 7808446
TI  - Cloning of a novel monoamine oxidase cDNA from trout liver.
AB  - A trout liver monoamine oxidase (MAO) cDNA was cloned by screening a cDNA library
      with a human MAO-A cDNA probe. The trout MAO cDNA encodes 499 amino acids, with a
      molecular mass of 56.6 kDa. The deduced amino acid sequence of trout MAO shows
      70% and 71% identity with those of human MAO-A and MAO-B, respectively. Trout MAO
      contains the pentapeptide sequence Ser-Gly-Gly-Cys-Tyr, to which the cofactor FAD
      is covalently bound. Transient expression of the cDNA in COS-7 cells shows that
      trout MAO oxidizes both serotonin [5-hydroxytryptamine (5-HT)] and beta
      phenylethylamine (PEA), unlike human MAO-A and MAO-B, which oxidize only 5-HT and
      PEA, respectively. The Km for 5-HT is similar for trout MAO (130 +/- 17 mM) and
      human MAO-A (68 +/- 4 mM). The Km for PEA is similar for trout MAO (12.5 +/- 2.0
      mM) and human MAO-B (1.5 +/- 0.2 mM). When 5-HT is used as a substrate, trout MAO
      is more sensitive to clorgyline (IC50, 2.8 +/- 0.2 x 10(-8) M) than deprenyl
      (IC50, 1.0 +/- 0.1 x 10(-6) M), a result similar to the inhibition selectivity of
      human MAO-A. However, trout MAO is less sensitive to clorgyline than is human MAO
      A (IC50, 5.8 +/- 0.1 x 10(-10) M). Trout MAO is less sensitive to deprenyl (IC50,
      4.6 +/- 0.3 x 10(-7) M) than is human MAO-B (IC50, 1.4 +/- 0.1 x 10(-9) M) when
      PEA is used as the substrate. These results indicate that trout MAO displays
      substrate and inhibitor selectivities that are not identical to those of either
      MAO-A and -B, and it therefore represents a novel type of MAO. The structure of
      trout MAO will provide insights into the substrate and inhibitor selectivities of
      the MAOs.

PMID- 7808447
TI  - Doxorubicin, daunorubicin, and mitoxantrone cytotoxicity in yeast.
AB  - We have investigated the effect of doxorubicin (Adriamycin) on the yeast
      Saccharomyces cerevisiae. Drug treatment was found to be cytotoxic to wild-type
      strains, in a concentration-dependent manner, whereas a petite mutant lacking the
      cytochrome oxidase (EC 1.9.3.1) subunit IV gene was resistant to doxorubicin.
      Transformation of the doxorubicin-resistant mutant with a yeast in vivo
      expression vector harboring the cytochrome oxidase subunit IV gene restored both
      respiration and sensitivity to doxorubicin. Another petite strain, with a
      mutation in the mitochondrial adenine nucleotide translocator (pet9), did not
      display doxorubicin resistance. However, in contrast to the subunit IV mutant, it
      possesses a functional respiratory chain. We also compared the cytotoxic effect
      of doxorubicin with those of daunorubicin and mitoxantrone in yeast. We found
      comparable levels of cytotoxicity for doxorubicin and daunorubicin, which were
      significantly greater than that for mitoxantrone. Finally, we constructed a yeast
      strain that overexpresses manganese superoxide dismutase (EC 1.15.1.1), an
      antioxidant enzyme present in mitochondria. Overexpression of manganese
      superoxide dismutase protected significantly against doxorubicin and daunorubicin
      cytotoxicity but only slightly against mitoxantrone cytotoxicity. Collectively,
      our results provide direct in vivo evidence that superoxide radicals participate
      in doxorubicin- and daunorubicin-induced cytotoxicity in yeast. Furthermore,
      these results indicate that mitochondrial respiration is a crucial factor in
      anthracycline, and perhaps mitoxantrone, cytotoxicity in yeast.

PMID- 7808448
TI  - Influence of mitochondrial creatine kinase on the
      mitochondrial/extramitochondrial distribution of high energy phosphates in muscle
      tissue: evidence for a leak in the creatine shuttle.
AB  - The influence of mitochondrial creatine kinase on subcellular high energy systems
      has been investigated using isolated rat heart mitochondria, mitoplasts and
      intact heart and skeletal muscle tissue. In isolated mitochondria, the creatine
      kinase is functionally coupled to oxidative phosphorylation at active respiratory
      chain, so that it catalyses the formation of creatine phosphate against its
      thermodynamic equilibrium. Therefore the mass action ratio is shifted from the
      equilibrium ratio to lower values. At inhibited respiration, it is close to the
      equilibrium value, irrespective of the mechanism of the inhibition. The same
      results were obtained for mitoplasts under conditions where the mitochondrial
      creatine kinase is still associated with the inner membrane. In intact tissue
      increasing amounts of creatine phosphate are found in the mitochondrial
      compartment when respiration and/or muscle work are increased. It is suggested
      that at high rates of oxidative phosphorylation creatine phosphate is accumulated
      in the intermembrane space due to the high activity of mitochondrial creatine
      kinase and the restricted permeability of reactants into the extramitochondrial
      space. A certain amount of this creatine phosphate 'leaks' into the mitochondrial
      matrix. This leak is confirmed in isolated rat heart mitochondria where creatine
      phosphate is taken up when it is generated by the mitochondrial creatine kinase
      reaction. At inhibited creatine kinase, external creatine phosphate is not taken
      up. Likewise, mitoplasts only take up creatine phosphate when creatine kinase is
      still associated with the inner membrane. Both findings indicate that uptake is
      dependent on the functional active creatine kinase coupled to oxidative
      phosphorylation. Creatine phosphate uptake into mitochondria is inhibited with
      carboxyatractyloside.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7808449
TI  - The structure of mitochondrial creatine kinase and its membrane binding
      properties.
AB  - The biochemical and biophysical characterization of the mitochondrial creatine
      kinase (Mi-CK) from chicken cardiac muscle is reviewed with emphasis on the
      structure of the octameric oligomer by electron microscopy and on its membrane
      binding properties. Information about shape, molecular symmetry and dimensions of
      the Mi-CK octamer, as obtained by different sample preparation techniques in
      combination with image processing methods, are compared. The organization of the
      four dimeric subunits into the Mi-CK complex as apparent as apparent in the end
      on projections is discussed and the consistently observed high binding affinity
      of the four-fold symmetric end-on faces towards many support films and towards
      each other is outlined. A study on the oligomeric state of the enzyme in solution
      and in intact mitochondria, using chemical crosslinking reagents, is presented
      together with the results of a search for a possible linkage of Mi-CK with the
      adenine nucleotide translocator (ANT). The nature of Mi-CK binding to model
      membranes, demonstrating that rather the octameric than the dimeric subspecies is
      involved in lipid interaction and membrane contact formation, is resumed and put
      into relation to our structural observations. The findings are discussed in light
      of a possible in vivo function of the Mi-CK octamer bridging the gap between
      outer and inner mitochondrial membranes at the contact sites.

PMID- 7808450
TI  - Myofibrillar creatine kinase and cardiac contraction.
AB  - This article is a review on the organization and function of myofibrillar
      creatine kinase in striated muscle. The first part describes myofibrillar
      creatine kinase as an integral structural part of the complex organization of
      myofibrils in striated muscle. The second part considers the intrinsic
      biochemical and mechanical properties of myofibrils and the functional coupling
      between myofibrillar CK and myosin ATPase. Skinned fiber studies have been
      developed to evidence this functional coupling and the consequences for cardiac
      contraction. The data show that creatine kinase in myofibrils is effective enough
      to sustain normal tension and relaxation, normal Ca sensitivity and kinetic
      characteristics. Moreover, the results suggest that myofibrillar creatine kinase
      is essential in maintaining adequate ATP/ADP ratio in the vicinity of myosin
      ATPase active site to prevent dysfunctioning of this enzyme. Implications for the
      physiology and physiopathology of cardiac muscle are discussed.

PMID- 7808452
TI  - Interaction of creatine kinase and adenylate kinase systems in muscle cells.
AB  - Elsewhere in this book the important role of creatine kinase and its metabolites
      in high energy phosphate metabolism and transport in muscle cells has been
      reviewed. The emphasis of this review article is mainly on the compartmentalized
      catalytic activity of adenylate kinase in relation to creatine kinase isoenzymes,
      and other enzymes of energy production and utilization processes in muscle cells.
      At present the role of adenylate kinase is considered simply to equilibrate the
      stores of adenine nucleotides. Recent studies by us and others, however, suggest
      an entirely new view of the metabolic importance of adenylate kinase in muscle
      function. This view offers a closer interaction between adenylate kinase and
      creatine kinase, in the process of energy production (at mitochondrial and
      glycolytic sites), and energy utilization (at myofibrillar sites and perhaps
      other sites such as sarcoplasmic reticular, sarcolemmal membrane, etc.), thus
      being an integral part of the high energy phosphate transport system. This review
      article opens up the opportunity to further examine the metabolism of adenine
      nucleotides and their fluxes through the adenylate kinase system in intact muscle
      cells. Using an intact system, having a preserved integrity of their
      compartmentalized enzymes and substrates, is essential in clarifying the exact
      role of adenylate kinase in high energy phosphate metabolism in muscle cells.

PMID- 7808451
TI  - Metabolic regulation of in vivo myocardial contractile function: multiparameter
      analysis.
AB  - To gain insight into the mechanisms of myocardial regulation as it relates to the
      interaction of mechanical and metabolic function and perfusion, intact animal
      models were instrumented for routine physiological measurements of mechanical
      function and for measurements of metabolism (31P NMR, NADH fluorescence (redox
      state)) and perfusion (2H NMR and Laser doppler techniques). These techniques
      were applied to canine and cat models of volume and/or pressure loading, hypoxia,
      ischemia and cardiomyopathic states. Data generated using these techniques
      indicate that myocardial bioenergetic function is quite stable under most loading
      conditions as long as the heart is not ischemic. In addition, these data indicate
      that there is no universal regulator and that different biochemical regulators
      appear to mediate stable function under different physiological and
      pathophysiological conditions: for example; during hypoxia, NADH redox state
      appears to play a regulatory role; and in pressure loading, ADP, phosphorylation
      potential and free energy of ATP hydrolysis as well as NADH redox state appear to
      be regulatory.

PMID- 7808455
TI  - The creatine kinase system in smooth muscle.
AB  - Despite the energetic flux being much lower in smooth muscle compared to striated
      muscles (such as the heart and skeletal muscle) creatine kinase (CK) has been
      found present and active in all smooth muscles studied to date. A complete CK
      circuit has been identified, with CK found in the mitochondria, contractile
      elements, membrane pumps and the cytoplasm. CK isoenzymes are coupled to many
      cellular energetic processes and appears to be involved in energy production and
      consumption by acting as an energy transducer. The CK system responds to
      pathological insults and development (e.g., hypertrophy and gestation
      respectively) by changes in sub-cellular distribution localization, isoenzymes,
      and specific activity. The conclusion from these observations is that creatine
      kinase is intimately involved in the energetic system of smooth muscle.

PMID- 7808456
TI  - Expression of the mitochondrial creatine kinase genes.
AB  - Mitochondrial Creatine Kinase (MtCK) is responsible for the transfer of high
      energy phosphate from mitochondria to the cytosolic carrier, creatine, and exists
      in mammals as two isoenzymes encoded by separate genes. In rats and humans,
      sarcomere-specific MtCK (sMtCK) is expressed only in skeletal and heart muscle,
      and has 87% nucleotide identity across the 1257 bp coding region. The ubiquitous
      isoenzyme of MtCK (uMtCK) is expressed in many tissues with highest levels in
      brain, gut, and kidney, and has 92% nucleotide identity between the 1254 bp
      coding regions of rat and human. Both genes are highly regulated developmentally
      in a tissue-specific manner. There is virtually no expression of sMtCK mRNA prior
      to birth. Unlike cytosolic muscle CK (MCK) and brain CK (BCK), there is no
      developmental isoenzyme switch between the MtCKs. Cell culture models
      representing the tissue-specific expression of either sMtCK or uMtCK are
      available, but there are no adequate developmental models to examine their
      regulation. Several animal models are available to examine the coordinate
      regulation of the CK gene family and include 1) Cardiac Stress by coarctation
      (sMtCK, BCK, and MCK), 2) Uterus and placenta during pregnancy (uMtCK and BCK),
      and 3) Diabetes and mitochondrial myopathy (sMtCK, BCK, and MCK). We report the
      details of these findings, and discuss the coordinate regulation of the genes
      necessary for high-energy transduction.

PMID- 7808453
TI  - Metabolic compartmentation and substrate channelling in muscle cells. Role of
      coupled creatine kinases in in vivo regulation of cellular respiration--a
      synthesis.
AB  - The published experimental data and existing concepts of cellular regulation of
      respiration are analyzed. Conventional, simplified considerations of regulatory
      mechanism by cytoplasmic ADP according to Michaelis-Menten kinetics or by derived
      parameters such as phosphate potential etc. do not explain relationships between
      oxygen consumption, workload and metabolic state of the cell. On the other hand,
      there are abundant data in literature showing microheterogeneity of cytoplasmic
      space in muscle cells, in particular with respect to ATP (and ADP) due to the
      structural organization of cell interior, existence of multienzyme complexes and
      structured water phase. Also very recent experimental data show that the
      intracellular diffusion of ADP is retarded in cardiomyocytes because of very low
      permeability of the mitochondrial outer membrane for adenine nucleotides in vivo.
      Most probably, permeability of the outer mitochondrial membrane porin channels is
      controlled in the cells in vivo by some intracellular factors which may be
      connected to cytoskeleton and lost during mitochondrial isolation. All these
      numerous data show convincingly that cellular metabolism cannot be understood if
      cell interior is considered as homogenous solution, and it is necessary to use
      the theories of organized metabolic systems and substrate-product channelling in
      multienzyme systems to understand metabolic regulation of respiration. One of
      these systems is the creatine kinase system, which channels high energy
      phosphates from mitochondria to sites of energy utilization. It is proposed that
      in muscle cells feed-back signal between contraction and mitochondrial
      respiration may be conducted by metabolic wave (propagation of oscillations of
      local concentration of ADP and creatine) through cytoplasmic equilibrium creatine
      and adenylate kinases and is amplified by coupled creatine kinase reaction in
      mitochondria. Mitochondrial creatine kinase has experimentally been shown to be a
      powerful amplifier of regulatory action of weak ADP fluxes due to its coupling to
      adenine nucleotide translocase. This phenomenon is also carefully analyzed.

PMID- 7808457
TI  - Sequence homology and structure predictions of the creatine kinase isoenzymes.
AB  - Comparisons of the protein sequences and gene structures of the known creatine
      kinase isoenzymes and other guanidino kinases revealed high homology and were
      used to determine the evolutionary relationships of the various guanidino
      kinases. A 'CK framework' is defined, consisting of the most conserved sequence
      blocks, and 'diagnostic boxes' are identified which are characteristic for anyone
      creatine kinase isoenzyme (e.g. for vertebrate B-CK) and which may serve to
      distinguish this isoenzyme from all others (e.g. from M-CKs and Mi-CKs).
      Comparison of the guanidino kinases by near-UV and far-UV circular dichroism
      further indicates pronounced conservation of secondary structure as well as of
      aromatic amino acids that are involved in catalysis.

PMID- 7808454
TI  - Creatine kinase in non-muscle tissues and cells.
AB  - Over the past years, a concept for creatine kinase function, the 'PCr-circuit'
      model, has evolved. Based on this concept, multiple functions for the CK/PCr
      system have been proposed, such as an energy buffering function, regulatory
      functions, as well as an energy transport function, mostly based on studies with
      muscle. While the temporal energy buffering and metabolic regulatory roles of CK
      are widely accepted, the spatial buffering or energy transport function, that is,
      the shuttling of PCr and Cr between sites of energy utilization and energy
      demand, is still being debated. There is, however, much circumstantial evidence,
      that supports the latter role of CK including the distinct, isoenzyme-specific
      subcellular localization of CK isoenzymes, the isolation and characterization of
      functionally coupled in vitro microcompartments of CK with a variety of cellular
      ATPases, and the observed functional coupling of mitochondrial oxidative
      phosphorylation with mitochondrial CK. New insight concerning the functions of
      the CK/PCr-system has been gained from recent M-CK null-mutant transgenic mice
      and by the investigation of CK localization and function in certain highly
      specialized non-muscle tissues and cells, such as electrocytes, retina
      photoreceptor cells, brain cells, kidney, salt glands, myometrium, placenta,
      pancreas, thymus, thyroid, intestinal brush-border epithelial cells, endothelial
      cells, cartilage and bone cells, macrophages, blood platelets, tumor and cancer
      cells. Studies with electric organ, including in vivo 31P-NMR, clearly reveal the
      buffer function of the CK/PCr-system in electrocytes and additionally corroborate
      a direct functional coupling of membrane-bound CK to the Na+/K(+)-ATPase. On the
      other hand, experiments with live sperm and recent in vivo 31P-NMR measurements
      on brain provide convincing evidence for the transport function of the CK/PCr
      system. We report on new findings concerning the isoenzyme-specific cellular
      localization and subcellular compartmentation of CK isoenzymes in photoreceptor
      cells, in glial and neuronal cells of the cerebellum and in spermatozoa. Finally,
      the regulation of CK expression by hormones is discussed, and new developments
      concerning a connection of CK with malignancy and cancer are illuminated. Most
      interesting in this respect is the observed upregulation of CK expression by
      adenoviral oncogenes.

PMID- 7808459
TI  - Compartmentation of creatine kinases during perinatal development of mammalian
      heart.
AB  - Maturation of the cardiac cell is characterized by increasing diversity of
      isozymic expression of creatine kinases. Expression of the M-CK isozyme always
      precedes that of mitochondrial isozyme (mi-CK), however the expression of an
      isoform does not inform about its localization or cellular function. The
      functional role of isozymes binding to sites of energy utilization and production
      characteristic of the adult myocardium can be evidenced by the functional
      coupling of M-CK to myofibrillar ATPase and mito-CK to translocase in Triton X
      100 and saponin skinned fibers. Functional activity of M-CK and mito-CK were
      investigated during perinatal development. Both functional activities appear
      during late fetal life in species mature at birth like guinea pig, and in the
      first postnatal weeks in immature species like rat or rabbit. Thus, the
      functional activity of bound CK isozymes is not associated with birth per se but
      with the general process of cell maturation. Localization of CK in the cytosol
      appears optimal for the transfer of glycolytic production of ATP to sites of
      utilization in an immature heart. During cell maturation, the increasing
      contribution of oxidative phosphorylation to ATP production, the apparition and
      binding of mi-CK to mitochondria, the binding of M-CK to myofibrils, turn the
      cell in a compartmentalized system of energy production. This provides the
      cellular basis for energy transfer by the PCr-Cr-CK system between sites of ATP
      production and utilization. Compartmentation of both Ca handling and energy
      turnover leads to a highly structured cell organization and could be essential
      for the efficiency of heart function.

PMID- 7808460
TI  - In situ study of myofibrils, mitochondria and bound creatine kinases in
      experimental cardiomyopathies.
AB  - Human cardiomyopathy has been extensively studied in the last decade, and
      knowledge of the functional and structural alterations of the heart has grown.
      However, understanding of the pathogenesis has come mostly from experimental
      studies. A number of work have been designed to elucidate if alterations of the
      contractile apparatus of cardiac cells contribute to the impairment of heart
      mechanics in cardiomyopathies. As well, an important question is to be solved:
      whether energy supply of the contraction-relaxation cycle is sufficient in the
      myopathic heart. Use of cardiac fibers skinned by different techniques allows to
      evaluate functional ability of myofibrils, mitochondria and bound creatine kinase
      which plays an important role in cardiomyocyte energy metabolism. The data
      presented in this chapter show that experimental cardiomyopathies of various
      types have some common features. These are an increase in calcium sensitivity of
      myofibrils and a depression of functional activity of mitochondrial creatine
      kinase. Possible mechanisms and physiological significance of these changes are
      discussed.

PMID- 7808458
TI  - Approaching the multifaceted nature of energy metabolism: inactivation of the
      cytosolic creatine kinases via homologous recombination in mouse embryonic stem
      cells.
AB  - To study the physiological role of the creatine kinase/phosphocreatine (CK/PCr)
      system in cells and tissues with a high and fluctuating energy demand we have
      concentrated on the site-directed inactivation of the B- and M-CK genes encoding
      the cytosolic CK protein subunits. In our approach we used homologous
      recombination in mouse embryonic stem (ES) cells from strain 129/Sv. Using
      targeting constructs based on strain 129/Sv isogenic DNA we managed to ablate the
      essential exons of the B-CK and M-CK genes at reasonably high frequencies. ES
      clones with fully disrupted B-CK and two types of M-CK gene mutations, a null (M
      CK-) and leaky (M-CK1) mutation, were used to generate chimaeric mutant mice via
      injection in strain C57BL/6 derived blastocysts. Chimaeras with the B-CK null
      mutation have no overt abnormalities but failed to transmit the mutation to their
      offspring. For the M-CK- and M-CK1 mutations successful transmission was achieved
      and heterozygous and homozygous mutant mice were bred. Animals deficient in MM-CK
      are phenotypically normal but lack muscular burst activity. Fluxes through the CK
      reaction in skeletal muscle are highly impaired and fast fibres show adaptation
      in cellular architecture and storage of glycogen. Mice homozygous for the leaky M
      CK allele, which have 3-fold reduced MM-CK activity, show normal fast fibres but
      CK fluxes and burst activity are still not restored to wildtype levels.

PMID- 7808461
TI  - Thyroid hormones and the creatine kinase system in cardiac cells.
AB  - The paper reviews the current evidence on the role of thyroid hormones in
      regulating the creatine kinase energy transfer system at multiple structures in
      cardiac cells. 1) Thyroid hormones modulate the overall synthesis of
      phosphocreatine (PCr) by increasing the rate of mitochondrial oxidative
      phosphorylation. 2) Thyroid hormones regulate the total activity of creatine
      kinase and its isoenzyme distribution. In comparison with normal thyroid state
      (euthyroidism), hypothyroidism is characterized by decreased total creatine
      kinase activity owing to diminished fraction of creatine kinase. On the other
      hand, hyperthyroidism, while causing no change in total creatine kinase activity,
      leads to increased fractions of neonatal isoforms of creatine kinase, and, in
      case of prolonged hyperthyroidism, to decreased fraction of mitochondrial
      creatine kinase. The latter change is associated with partial uncoupling between
      mitochondrial creatine kinase and adenine nucleotide translocase reflected by
      decreased PCr/O ratio. 3) Hyperthyroidism leads to increased passive sarcolemmal
      permeability due to which the leakage of creatine along its concentration
      gradient occurs. As a result of (i) increased sarcolemmal permeability for
      creatine, (ii) uncoupling of mitochondrial PCr synthesis, and (iii) increased
      energy utilization rate the steady state intracellular PCr content decreases
      under hyperthyroidism which, in turn, increases the myocardial susceptibility to
      hypoxic damage. Thyroid state also modulates the protective effects of exogenous
      PCr on energetically depleted myocardium.

PMID- 7808462
TI  - Control theory of metabolic channelling.
AB  - Various factors appear to control muscle energetics, often in conjunction. This
      calls for a quantitative approach of the type provided by Metabolic Control
      Analysis for intermediary metabolism and mitochondrial oxidative phosphorylation.
      To the extent that direct transfer of high energy phosphates and spatial
      organization plays a role in muscle energetics however, the standard Metabolic
      Control Theory does not apply, neither do its theorems regarding control. This
      chapter develops the Control Theory that does apply to the muscle system. It
      shows that direct transfer of high energy phosphates bestows a system with
      enhanced control: the sum of the control exerted by the participating enzymes on
      the flux of free energy form the mitochondrial matrix to the actinomyosin may
      well exceed the 100% mandatory for ideal metabolic pathways. It is also shown how
      sequestration of high energy phosphates may allow for negative control on pathway
      flux. The new control theory gives methods functionally to diagnose the extent to
      which channelling and metabolite sequestration occur.

PMID- 7808463
TI  - Mathematical modeling of intracellular transport processes and the creatine
      kinase systems: a probability approach.
AB  - A probability approach was used to describe mitochondrial respiration in the
      presence of substrates, ATP, ADP, Cr and PCr. Respiring mitochondria were
      considered as a three-component system, including: 1) oxidative phosphorylation
      reactions which provide stable ATP and ADP concentrations in the mitochondrial
      matrix; 2) adenine nucleotide translocase provides exchange transfer of matrix
      adenine nucleotides for those from outside, supplied from medium and by creatine
      kinase; 3) creatine kinase, starting these reactions when activated by the
      substrates from medium. The specific feature of this system is close proximity of
      creatine kinase and translocase molecules. This results in high probability of
      direct activation of translocase by creatine kinase-derived ADP or ATP without
      their leak into the medium. In turn, the activated translocase with the same high
      probability directly provides creatine kinase with matrix-derived ATP or ADP. The
      catalytic complexes of creatine kinase formed with ATP from matrix together with
      those formed from medium ATP provide activation of the forward creatine kinase
      reaction coupled to translocase activation. Simultaneously the catalytic
      complexes of creatine kinase formed with ADP from matrix together with those
      formed from medium ADP provide activation of the reverse creatine kinase reaction
      coupled to translocase activation. The considered probabilities were arranged
      into a mathematical model. The model satisfactorily simulates the available
      experimental data by several groups of investigators. The results allow to
      consider the observed kinetic and thermodynamic irregularities in behavior of
      structurally bound creatine kinase as a direct consequence of its tight coupling
      to translocase.

PMID- 7808464
TI  - Compartmentation of ATP synthesis and utilization in smooth muscle: roles of
      aerobic glycolysis and creatine kinase.
AB  - The phosphocreatine content of smooth muscle is of similar magnitude to ATP. Thus
      the function of the creatine kinase system in this tissue cannot simply be
      regarded as an energy buffer. Thus an understanding of its role in smooth muscle
      behavior can point to CK function in other systems. From our perspective CK
      function in smooth muscle is one example of a more general phenomenon, that of
      the co-localization of ATP synthesis and utilization. In an interesting and
      analogous fashion distinct glycolytic cascades are also localized in regions of
      the cell with specialized energy requirements. Similar to CK, glycolytic enzymes
      are known to be localized on thin filaments, sarcoplasmic reticulum and plasma
      membrane. In this chapter we will describe the relations between glycolysis and
      smooth muscle function and compare and contrast to that of the CK system. Our
      goal is to more fully understand the significance of the compartmentation of
      distinct pathways for ATP synthesis with specific functions in smooth muscle.
      This organization of metabolism and function seen most clearly in smooth muscle
      is likely representative of many other cell types.

PMID- 7808465
TI  - Creatine metabolism and the consequences of creatine depletion in muscle.
AB  - Currently, considerable research activities are focussing on biochemical,
      physiological and pathological aspects of the creatine kinase (CK)
      phosphorylcreatine (PCr)-creatine (Cr) system (for reviews see [1,2]), but only
      little effort is directed towards a thorough investigation of Cr metabolism as a
      whole. However, a detailed knowledge of Cr metabolism is essential for a deeper
      understanding of bioenergetics in general and, for example, of the effects of
      muscular dystrophies, atrophies, CK deficiencies (e.g. in transgenic animals) or
      Cr analogues on the energy metabolism of the tissues involved. Therefore, the
      present article provides a short overview on the reactions and enzymes involved
      in Cr biosynthesis and degradation, on the organization and regulation of Cr
      metabolism within the body, as well as on the metabolic consequences of 3
      guanidinopropionate (GPA) feeding which is known to induce a Cr deficiency in
      muscle. In addition, the phenotype of muscles depleted of Cr and PCr by GPA
      feeding is put into context with recent investigations on the muscle phenotype of
      'gene knockout' mice deficient in the cytosolic muscle-type M-CK.

PMID- 7808466
TI  - The importance of the outer mitochondrial compartment in regulation of energy
      metabolism.
AB  - Substitution of physiologically present macromolecules during isolation of
      mitochondria and investigation of their functions led to a significant change in
      regulation of oxidative phosphorylation. The differences compared to
      conventionally isolated mitochondria were that stimulation of oxidative
      phosphorylation appeared to rather depend on the activity of peripheral kinases
      than on the addition of free ADP. The localisation of peripheral kinases such as
      hexokinase and mitochondrial creatine kinase are described as well as the effects
      of macromolecules on the regulation of bound hexokinase and of oxidative
      phosphorylation via this enzyme.

PMID- 7808468
TI  - A brief summary of the history of the detection of creatine kinase isoenzymes.

PMID- 7808467
TI  - The influence of the cytosolic oncotic pressure on the permeability of the
      mitochondrial outer membrane for ADP: implications for the kinetic properties of
      mitochondrial creatine kinase and for ADP channelling into the intermembrane
      space.
AB  - Cytosolic proteins as components of the physiological mitochondrial environment
      were substituted by dextrans added to media normally used for incubation of
      isolated mitochondria. Under these conditions the volume of the intermembrane
      space decreases and the contact sites between the both mitochondrial membranes
      increase drastically. These morphological changes are accompanied by a reduced
      permeability of the mitochondrial outer compartment for adenine nucleotides as it
      was shown by extensive kinetic studies of mitochondrial enzymes (oxidative
      phosphorylation, mi-creatine kinase, mi-adenylate kinase). The decreased
      permeability of the mitochondrial outer membrane causes increased rate dependent
      concentration gradients in the micromolar range for adenine nucleotides between
      the intermembrane space and the extramitochondrial space. Although all
      metabolites crossing the outer membrane exhibit the same concentration gradients,
      considerable compartmentations are detectable for ADP only due to its low
      extramitochondrial concentration. The consequences of ADP-compartmentation in the
      mitochondrial intermembrane space for ADP-channelling into the mitochondria are
      discussed.

PMID- 7808469
TI  - Epitope mapping of monoclonal antibodies directed against lipophosphoglycan of
      Leishmania major promastigotes.
AB  - Monoclonal antibodies (MAbs) were generated against Leishmania major promastigote
      lipophosphoglycan (LPG) to use as tools in defining functional epitopes of this
      major cell surface glycoconjugate. Epitope mapping of four MAbs, designated 4A2
      A2, 2G11-A3, 5E6-D10 and 5E10-F2, revealed that the phosphorylated
      oligosaccharide repeat unit PO4-6[Gal(beta 1-3)]Gal(beta 1-4)Man alpha 1-, P3, is
      a highly immunogenic epitope which has previously been demonstrated, by chemical
      analyses, to be a repeat unit specific to L. major. Two antibodies, 4A2-A2 and
      5E10-F2, also recognised the repeat unit PO4-6[Ara(beta 1-2)Gal(beta 1
      3)]Gal(beta 1-4)Man alpha 1-, 4Pa, with less affinity than P3, while 2G11-A3
      recognised P4a with greater affinity than for P3. The L. major metacyclic
      specific antibody 3F12 only recognised repeat units terminating with arabinose
      residues. In particular, 3F12 recognised P4a, which is upregulated in metacyclic
      LPG compared to the procyclic form of the molecule. The oligosaccharides P3, P4a
      and P5a are specific to L. major LPG. The epitopes of 4A2-A2, 2G11-A3, 5E6-D10
      and 5E10-F2 were found on the cell surface and in the flagellar pocket of both
      procyclic and metacyclic V121 promastigotes, but were only detected at very low
      levels on amastigotes. The repeat unit P3 is able to inhibit attachment of
      procyclic promastigotes to the midgut of the sandfly vector, but neither Fab
      fragments of the four antibodies nor purified P3 could inhibit attachment of
      metacyclic promastigotes to the macrophage cell line J774. It was also shown that
      human sera from patients with cutaneous leishmaniasis recognised purified P3. The
      data suggests that while P3 is an immunogen in the natural course of infection of
      the human host, P3 plays no role in attachment and internalisation of
      promastigotes into the macrophages of the mammalian host.

PMID- 7808470
TI  - Identification by extrachromosomal amplification and overexpression of a zeta
      crystallin/NADPH-oxidoreductase homologue constitutively expressed in Leishmania
      spp.
AB  - A gene which overexpresses a 36-kDa protein (p36) in tunicamycin-resistant
      Leishmania was mapped by transfection and overexpression to the upstream region
      of the drug maker in the extrachromosomal amplicon. Complete sequencing of this
      region revealed a single open reading frame of about 1 kb. Authenticity of the
      cloned gene is verified by immunologic specificity of its recombinant products
      and sequence identity with a p36 peptide. The gene shares an overall sequence
      similarity of about 50% with members of the eukaryote alcohol dehydrogenase
      family at the amino acid level, including essentially all 13 evolutionarily
      conserved residues and a nucleotide-binding domain. The binding ligands for both
      structurally and catalytically important zinc atoms are absent, similar to the
      zeta-crystallin/NADPH:quinone oxidoreductase gene. Consistent with hydrophilicity
      of its primary sequence and the presence of a nucleotide binding site, p36 is a
      soluble molecule non-sedimentable at 105,000 x g and binds Blue Sepharose,
      elutable only with NADPH. The p36 gene is expressed constitutively in both stages
      of the wild-type and is conserved among all Leishmania species examined,
      suggestive of its functional significance different from evolutionarily related
      homologues.

PMID- 7808471
TI  - Human serum-sensitive Trypanosoma brucei rhodesiense: a comparison with
      serologically identical human serum-resistant clones.
AB  - Trypanosoma brucei rhodesiense clones, which are susceptible to lysis by normal
      human serum, were isolated from 3 different human serum-resistant clones
      originally derived from strain ETat 1.10. Serologically, these pairs of serum
      sensitive and serum-resistant clones displayed the same variant surface
      glycoprotein (VSG) on their surface. Acquisition of human serum sensitivity
      correlated with susceptibility to lysis by human high density lipoprotein, a
      trypanocidal factor in normal human serum. Analysis of these paired populations
      by two-dimensional gel electrophoresis of whole trypanosomes and various
      subcellular fractions failed to reveal any differences in mobility of VSG and
      other proteins. Northern blot analysis of mRNAs from serum-sensitive and serum
      resistant clones showed no differences when probed with a previously described
      resistance-specific probe. In addition, the ethanolamine membrane transport
      system and the overall membrane lipid fluidity did not reveal any detectable
      biochemical or biophysical differences in membrane properties. If resistance to
      lysis is indeed mediated by membrane changes at the enzymatic or structural
      level, the data presented suggest that the gene product(s) responsible for this
      change in human serum sensitivity may be present in very small quantities.

PMID- 7808472
TI  - Phylogenetic analysis of the rpoB gene from the plastid-like DNA of Plasmodium
      falciparum.
AB  - Malaria and other Apicomplexan parasites harbour two extrachromosomal DNAs. One
      is mitochondrial and the other is a 35-kb circle with some plastid-like features
      but whose provenance and function is unknown. In addition to genes for rRNAs,
      tRNAs and ribosomal proteins, the 35-kb circular DNA of Plasmodium falciparum
      carries an rpoBC operon which encodes subunits of a eubacteria-like RNA
      polymerase. The phylogenetic analysis of the complete rpoB sequence presented
      here supports our inference that the 35-kb circle is the remnant of a plastid
      genome.

PMID- 7808473
TI  - Sequencing and gene expression of hypodermins A, B, C in larval stages of
      Hypoderma lineatum.
AB  - The cDNAs of hypodermins, enzymes secreted by the larvae of the parasitic fly
      Hypoderma lineatum, were sequenced. Four cDNA clones were isolated, one encoding
      hypodermin A (HA), one encoding hypodermin C (HC), and the two others encoding
      proteins related to hypodermin B (HB). The amino acid sequences deduced from the
      nucleotide sequences confirmed that these enzymes are serine proteases. HA and
      one of the HB proteins had potential N-linked glycosylation sites. Analysis of
      hypodermin protein, RNA and DNA at different larval stages indicated that protein
      overexpression is regulated transcriptionally for HA and HB, and by
      transcriptional and DNA amplification for HC.

PMID- 7808474
TI  - Proof of intragenic recombination in Plasmodium falciparum.
AB  - Intragenic recombination in the merozoite surface protein MSP-1 of Plasmodium
      falciparum has been demonstrated in a cross between two cloned lines (3D7 and
      HB3) of this species. Following passage of a mixture of the clones through
      mosquitoes, uncloned progeny were examined by PCR for molecules containing
      sequences of both parent MSP-1 alleles. A recombinant molecule possessing both
      3D7 and HB3 sequences has been obtained. Such molecules were not obtained from
      artificial mixtures of the blood forms of each clone. It is concluded that the
      novel allele was formed by a recombination event during meiosis of a hybrid
      3D7/HB3 zygote.

PMID- 7808475
TI  - Evidence for two single copy units in Theileria parva ribosomal RNA genes.
AB  - Bacteriophage clones containing ribosomal RNA genes of Theileria parva were
      isolated from genomic DNA libraries. Physical mapping studies revealed 2
      ribosomal DNA units, which were distinguishable by restriction enzyme site
      polymorphisms in flanking sequences. The cloned ribosomal DNA units were mapped
      to 2 separate T. parva chromosomes. Analysis of sequences contained in lambda
      EMBL3 recombinants, together with Southern blot analysis of genomic DNA and data
      on the copy number of the rRNA genes, suggested that the rDNA units were not
      tandemly repeated. This organisation of ribosomal transcription units is similar
      to that described for other genera of apicomplexan protozoa, but 2 rDNA units,
      each containing single copies of the rRNA coding genes, would be the lowest copy
      number described for any eukaryote in which amplification of rRNA genes is not
      known to occur. EcoRI restriction fragment length polymorphisms, which were
      revealed using rRNA gene probes, separated T. parva stocks into 2 categories.
      Nucleotide sequence analysis of polymerase chain reaction-amplified internal
      transcribed spacer DNA revealed 2 different ITS sequences derived from rDNA
      transcription units within the genome of a cloned T. parva parasite. Polymorphism
      was also observed between ITS sequences amplified from the DNA of different T.
      parva stocks. A synthetic oligonucleotide derived from T. parva Uganda ribosomal
      ITS DNA sequences hybridised to DNA from the T. parva Uganda stock, but not to
      the DNA of the T. parva Muguga stock. This oligonucleotide is potentially useful
      as a marker for the T. parva Uganda stock.

PMID- 7808476
TI  - Mini-exon gene variation in human pathogenic Leishmania species.
AB  - We have used polymerase chain reaction to amplify the mini-exon gene repeat from
      18 Leishmania strains. DNA sequence analysis of the cloned products reveals high
      conservation of both the exon and intron (i.e. transcribed region). In contrast,
      variation is evident in both the length and primary sequence of the non
      transcribed spacers. Dermotropic species of the New World subgenus Leishmania
      possess a 0.3-kb gene that differs from the 0.25-kb gene of New World dermotropic
      species of the subgenus Viannia. The Old/New World viscerotropic species and Old
      World dermotropic species possess a 0.4-kb mini-exon gene. However, the genes
      from the viscerotropic and dermotropic groups may be distinguished on the basis
      of sequence differences in the non-transcribed spacer. Comparative analysis of
      the -86 to -1 region from all species has been used to measure relatedness within
      the genus. In general, all the observed differences correlate with the four major
      groups of Leishmania (New World dermotropic Leishmania, New World dermotropic
      Viannia, Old World dermotropic Leishmania and viscerotropic Leishmania). Two of
      the three repeats cloned from L. donovani show short deletions. The missing
      sequence is flanked by direct, 7-bp repeats suggesting that the sequences may
      have been deleted by homologous recombination. Such rearrangements could account
      for the diversity detected in the non-transcribed spacers of the mini-exon genes.

PMID- 7808477
TI  - Differential expression of two succinate dehydrogenase subunit-B genes and a
      transition in energy metabolism during the development of the parasitic nematode
      Haemonchus contortus.
AB  - The carbohydrate metabolism of free-living and parasitic stages of the sheep
      nematode Haemonchus contortus was studied, and it was demonstrated that during
      development a switch occurred from Krebs-cycle activity towards a more
      fermentative metabolism. During this switch a transition might take place in
      complex II of the respiratory chain. In the free-living (L3) and early parasitic
      (XL3) stages, complex II catalyses the oxidation of succinate to fumarate via the
      Krebs cycle, whereas in adults complex II functions in the reverse reaction, the
      reduction of fumarate to succinate. L3 and XL3 were shown to already possess a
      large anaerobic capacity. They survived well in the absence of oxygen or in the
      presence of cyanide, which completely blocked respiration. Krebs-cycle activity,
      however, was only partially inhibited by cyanide; the XL3s in particular produced
      in the presence of cyanide large amounts of propanol, the production of which
      probably functions as an alternative electron sink. For further investigation of
      the observed metabolic switch, complex II of the respiratory chain, a key enzyme
      involved in this switch, was studied. The B subunit of complex II was cloned and
      sequenced. These clones all showed sequences similar to the B subunit of
      succinate dehydrogenase from other species, and included the amino-terminal
      signal sequence for importation into mitochondria. Two genes were identified,
      types 1 and 2, based on the DNA and amino acid sequences and on the lack of cross
      reaction to each other when used as probes on Southern blots. On Northern blots,
      the two genes showed a different expression pattern during the development of the
      parasite.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7808478
TI  - Molecular characterization of a 65-kilodalton Toxoplasma gondii antigen expressed
      abundantly in the matrix of tissue cysts.
AB  - We describe the cloning and characterization of a novel antigen expressed in the
      bradyzoite stage of Toxoplasma gondii. A cDNA library was constructed in
      bacteriophage lambda gt11 Sfi-Not using messenger RNA molecules isolated from
      cysts of the ME49 strain of T. gondii. The recombinant phage library was
      subjected to screening with polyclonal antibodies against bradyzoite antigens.
      This screening identified a recombinant antigen that was recognized strongly by
      polyclonal antibodies against bradyzoite antigens as well as by sera from mice
      chronically infected with T. gondii. The native antigen is a protein of 65 kDa
      that localized to the matrix of the cyst and the cyst wall surrounding the
      bradyzoites. The antigen was found to be expressed abundantly in cysts but could
      not be detected in tachyzoites or within the parasitophorous vacuole of
      tachyzoite infected host cells. Genomic and cDNA sequence of the gene revealed an
      open reading frame encoding 452 amino acids interrupted by 2 introns: a 503-bp
      intron located in the 5' untranslated region preceding the protein coding
      sequence and a 110-bp intron located 95 bp downstream of the first ATG.

PMID- 7808479
TI  - Primary structure of the hydrogenosomal adenylate kinase of Trichomonas vaginalis
      and its phylogenetic relationships.
AB  - Hydrogenosomal adenylate kinase of the amitochondriate protist, Trichomonas
      vaginalis, has been purified and the sequence of its 39 amino-terminal residues
      established. Based on this sequence and a conserved internal region of the
      enzyme, a probe was obtained by DNA polymerase chain reaction and used to isolate
      a genomic DNA clone containing the gene of this enzyme. This gene exists probably
      as a single copy in T. vaginalis and is not interrupted by introns. The open
      reading frame obtained codes for a large type adenylate kinase with a mature
      molecular mass of 24.5 kDa. The T. vaginalis enzyme is homologous with adenylate
      kinases of other eukaryotes and eubacteria. Strongly conserved parts and residues
      of the molecule are conserved also in this enzyme. Phylogenetic trees obtained
      with various methods placed the T. vaginalis adenylate kinase close to the point
      where the different subfamilies of this enzyme branch from each other, indicating
      that the T. vaginalis enzyme has no close relationship to any of these
      subfamilies and that it separated early from other adenylate kinases. The
      conceptual translation predicts the existence of an amino-terminal nonapeptide
      absent from the protein purified from hydrogenosomes, similar to the processed
      amino-terminal extensions of other hydrogenosomal proteins. These extensions have
      been considered as putative targeting and import signals.

PMID- 7808480
TI  - Molecular characterization of the alpha-subunit of Trichomonas vaginalis
      hydrogenosomal succinyl CoA synthetase.
AB  - The anaerobic, parasitic protist, Trichomonas vaginalis, is characterized by the
      absence of mitochondria and the presence of double membrane bound organelles
      called hydrogenosomes. Succinyl-coenzyme A synthetase is a hydrogenosomal enzyme
      which catalyzes the formation of ATP via substrate-level phosphorylation. We have
      characterized genes encoding the alpha subunit of the hydrogenosomal protein
      succinyl-coenzyme A synthetase (SCS). The alpha-SCS of T. vaginalis is encoded by
      a multigene family composed of 3 similar genes that do not appear allelic. These
      3 alpha-SCS genes encode a protein with a calculated molecular mass of
      approximately 32.5 kDa that has > 50% identity (> 70% similarity with alpha-SCSs
      from Escherichia coli, Thermus flavus, and rat liver mitochondria. Antibodies
      raised against recombinant T vaginalis alpha-SCS expressed in bacteria were used
      to isolate alpha-SCS proteins from purified hydrogenosomes. These proteins
      partition into the soluble fraction of hydrogenosomes treated with sodium
      carbonate at high pH, consistent with a matrix localization in the organelle.
      Amino-terminal sequencing of purified alpha-SCS proteins shows that mature
      proteins lack a short, leader sequence of 9 amino acids. These amino terminal
      sequences which are cleaved from T. vaginalis alpha-SCSs are similar to each
      other and to all other leader sequences identifed on hydrogenosomal proteins.

PMID- 7808481
TI  - Recognition of the major cell surface glycoconjugates of Leishmania parasites by
      the human serum mannan-binding protein.
AB  - Activation of complement on the surface of parasitic protozoa of the genus
      Leishmania appears to be important for parasite infectivity in the mammalian
      host, as it allows these parasites to attach to and invade macrophages via their
      surface complement receptors. Serum mannan-binding protein (MBP) is a known
      activator of complement. Therefore, in the present study, we have investigated
      whether serum MBP binds to live Leishmania parasites, and to mannose-containing
      saccharides derived from the parasite cell surface. We have observed by
      fluorescence microscopy that biotinylated MBP binds to the surface of L. major
      and L. mexicana promastigotes. At this developmental stage the parasites are
      coated by a mannose-containing lipophosphoglycan (LPG). We have observed that
      radioiodinated MBP binds in a mannose-inhibitable manner to purified LPG which
      has been immobilized in plastic microwells, as well as to purified mannose
      terminating di-, tri- and tetrasaccharide fragments ('cap' structures) which have
      been released by mild acid hydrolysis from the outer chains of the LPG, converted
      into neoglycolipids and resolved by thin-layer chromatography. 125I-MBP also
      binds in the chromatogram-binding assay to the mannose-containing glycoinositol
      phospholipids that are expressed in high copy number on both the promastigote and
      the intracellular amastigote stages of most Leishmania species. These data
      suggest that MBP has the potential to opsonize the major developmental stages of
      Leishmania parasites, and provide a possible mechanism for the antibody
      independent activation of complement on their surface.

PMID- 7808482
TI  - Plasmodium falciparum calcium-dependent protein kinase phosphorylates proteins of
      the host erythrocytic membrane.
AB  - The unusual Ca(2+)-dependent protein kinase from Plasmodium falciparum (PfCPK)
      [1], whose gene structure and expression in bacteria have been reported [1], was
      purified to homogeneity. The purified recombinant kinase has a native molecular
      mass of 62,000, is activated by Ca2+ (K0.5 = 15 microM) in the presence of Mg2+
      or Mn2+, and can associate with 45Ca2+. The activation by Ca2+ could be partially
      replaced by Mn2+, but not by Zn2+ or Mg2+. PfCPK preferentially phosphorylated
      casein and histone H1. The Km and Vmax for Mg2+ ATP were 26 microM and 70 nmol
      min-1 mg-1, respectively, with casein as substrate; and 34 microM and 143 nmol
      min-1 mg-1, respectively, with histone H1 as substrate. The kinase undergoes
      autophosphorylation on both serine and threonine residues. Calmodulin antagonists
      (calmidazolium, trifluoperazine, N-[6-aminohexyl]-5-chloro-1-napthalene
      sulfonamide, and ophiobolin A) could inhibit the kinase activation, but much
      higher concentrations of the antagonists are needed than was required to inhibit
      calmodulin-mediated effects. PfCPK preferentially phosphorylates proteins of the
      host erythrocytic membrane in vitro but phosphorylates parasitic proteins only to
      a minor extent. The selectivity of the phosphorylation may be partially
      controlled by phosphatidylserine which is bound to some of the erythrocytic
      membrane proteins. Using a rabbit polyclonal antiserum against the recombinant
      protein, the kinase was found to be mainly expressed in the ring and schizont
      stages, and mainly localized in the parasitic membrane-organelle fraction and
      partially localized on the erythrocytic membrane.

PMID- 7808483
TI  - Genetic rescue of surface metalloproteinase (gp63)-deficiency in Leishmania
      amazonensis variants increases their infection of macrophages at the early phase.

PMID- 7808484
TI  - Cloning and expression of cDNA encoding an Eimeria acervulina 70 kDa sporozoite
      protein which is related to the 70 kDa heat-shock protein family.

PMID- 7808485
TI  - Virologic and immunologic characterization of long-term survivors of human
      immunodeficiency virus type 1 infection.
AB  - BACKGROUND: In most subjects infected with human immunodeficiency virus type 1
      (HIV-1), clinical or laboratory evidence of immunodeficiency develops within 10
      years of seroconversion, but a few infected people remain healthy and
      immunologically normal for more than a decade. Studies of these subjects, termed
      long-term survivors, may yield important clues for the development of
      prophylactic and therapeutic interventions against the acquired immunodeficiency
      syndrome. METHODS AND RESULTS: We studied 10 seropositive subjects who remained
      asymptomatic with normal and stable CD4+ lymphocyte counts despite 12 to 15 years
      of HIV-1 infection. Plasma cultures were uniformly negative for infectious virus.
      However, particle-associated HIV-1 RNA was detected in four subjects with a
      sensitive branched-DNA signal-amplification assay, whereas in five others the
      levels of HIV-1 RNA were too low to detect. Infectious HIV-1 was detected in
      peripheral-blood mononuclear cells (PBMC) of three subjects by standard limiting
      dilution cultures, and infectious virus was recovered from another subject with
      use of a CD8-depleted culture. The other six subjects had no detectable
      infectious virus in their PBMC. A quantitative polymerase-chain-reaction assay
      revealed that all subjects had detectable but low titers of viral DNA in PBMC.
      Overall, the viral burden in the plasma and PBMC of long-term survivors was
      orders of magnitude lower than that typically found in subjects with progressive
      disease. There was no in vitro evidence of resistance by host CD4+ lymphocytes to
      HIV-1 infection. However, long-term survivors had a vigorous, virus-inhibitory
      CD8+ lymphocyte response and a strong neutralizing-antibody response. In two
      subjects the kinetics of viral replication were consistent with the presence of a
      substantially attenuated strain of HIV-1. CONCLUSIONS: Subjects who remain
      asymptomatic for many years despite HIV-1 infection have low levels of HIV-1 and
      a combination of strong virus-specific immune responses with some degree of
      attenuation of the virus.

PMID- 7808486
TI  - Studies in subjects with long-term nonprogressive human immunodeficiency virus
      infection.
AB  - BACKGROUND: In a small percentage of persons infected with human immunodeficiency
      virus type 1 (HIV-1), there is no progression of disease and CD4+ T-cell counts
      remain stable for many years. Studies of the histopathological, virologic, and
      immunologic characteristics of these persons may provide insight into the
      pathogenic mechanisms that lead to HIV disease and the protective mechanisms that
      prevent progression to overt disease. METHODS AND RESULTS: We studied 15 subjects
      with long-term nonprogressive HIV infection and 18 subjects with progressive HIV
      disease. Nonprogressive infection was defined as seven or more years of
      documented HIV infection, with more than 600 CD4+ T cells per cubic millimeter,
      no antiretroviral therapy, and no HIV-related disease. Lymph nodes from the
      subjects with nonprogressive infection had significantly fewer of the
      hyperplastic features, and none of the involuted features, characteristic of
      nodes from subjects with progressive disease. Plasma levels of HIV-1 RNA and the
      viral burden in peripheral-blood mononuclear cells were both significantly lower
      in the subjects with nonprogressive infection than in those with progressive
      disease (P = 0.003 and P = 0.015, respectively). HIV could not be isolated from
      the plasma of the former, who also had significantly higher titers of
      neutralizing antibodies than the latter. There was viral replication, however, in
      the subjects with nonprogressive infection, and virus was consistently cultured
      from mononuclear cells from the lymph nodes. In the lymph nodes virus "trapping"
      varied with the degree of formation of germinal centers, and few cells expressing
      virus were found by in situ hybridization. HIV-specific cytotoxic activity was
      detected in all seven subjects with nonprogressive infection who were tested.
      CONCLUSIONS: In persons who remain free of disease for many years despite HIV
      infection the viral load is low, but viral replication persists. Lymph-node
      architecture and immune function appear to remain intact.

PMID- 7808487
TI  - Autologous or allogeneic bone marrow transplantation compared with intensive
      chemotherapy in acute myelogenous leukemia. European Organization for Research
      and Treatment of Cancer (EORTC) and the Gruppo Italiano Malattie Ematologiche
      Maligne dell'Adulto (GIMEMA) Leukemia Cooperative Groups.
AB  - BACKGROUND: Allogeneic or autologous bone marrow transplantation and intensive
      consolidation chemotherapy are used to treat acute myelogenous leukemia in a
      first complete remission. METHODS: After induction treatment with daunorubicin
      and cytarabine, patients who had a complete remission received a first course of
      intensive consolidation chemotherapy, combining intermediate-dose cytarabine and
      amsacrine. Patients with an HLA-identical sibling were assigned to undergo
      allogeneic bone marrow transplantation; the others were randomly assigned to
      undergo autologous bone marrow transplantation (with unpurged bone marrow) or a
      second course of intensive chemotherapy, combining high-dose cytarabine and
      daunorubicin. Comparisons were made on the basis of the intention to treat.
      RESULTS: A total of 623 patients had a complete remission; 168 were assigned to
      undergo allogeneic bone marrow transplantation, and 254 were randomly assigned to
      one of the other two groups. Of these patients, 343 completed the treatment
      assignment: 144 in the allogeneic-transplantation group, 95 in the autologous
      transplantation group, and 104 in the intensive-chemotherapy group. The relapse
      rate was highest in the intensive-chemotherapy group and lowest in the allogeneic
      transplantation group, whereas the mortality rate was highest after allogeneic
      transplantation and lowest after intensive chemotherapy. The projected rate of
      disease-free survival at four years was 55 percent for allogeneic
      transplantation, 48 percent for autologous transplantation, and 30 percent for
      intensive chemotherapy. However, the overall survival after complete remission
      was similar in the three groups, since more patients who relapsed after a second
      course of intensive chemotherapy had a response to subsequent autologous bone
      marrow transplantation. Other differences were also observed, especially with
      regard to hematopoietic recovery (it occurred later after autologous
      transplantation) and the duration of hospitalization (it was longer with bone
      marrow transplantation). CONCLUSIONS: Autologous as well as allogeneic bone
      marrow transplantation results in better disease-free survival than intensive
      consolidation chemotherapy with high-dose cytarabine and daunorubicin.
      Transplantation soon after a relapse or during a second complete remission might
      also be appropriate.

PMID- 7808488
TI  - Preliminary experience with endoscopic laser surgery for severe twin-twin
      transfusion syndrome.
AB  - BACKGROUND: In monozygotic twin pregnancies, there are placental vascular
      communications between the two fetuses. In 15 percent of such pregnancies there
      is an imbalance in net blood flow between the twins, resulting in the twin-twin
      transfusion syndrome. The recipient twin may have severe hydramnios during the
      second trimester of pregnancy, and there is a high risk of perinatal death and
      cerebral palsy in survivors. This condition can now be treated by endoscopic
      coagulation of the vascular anastomoses responsible for fetofetal transfusion
      with a neodymium:yttrium-aluminum-garnet (Nd: YAG) laser. METHODS: We performed
      intrauterine surgery in 45 pregnant women carrying twins at 15 to 28 weeks of
      gestation (median, 21); in each case there was severe hydramnios in one fetus due
      to the twin-twin transfusion syndrome. With the use of local anesthesia and
      continuous ultrasound visualization, a rigid fetoscope 2 mm in diameter, housed
      in a 2.7-mm cannula, was introduced transabdominally into the amniotic cavity of
      the recipient twin. A systematic search was made for all vessels approaching or
      crossing the membrane between the twins, and these were coagulated with an Nd:YAG
      laser by means of a fiber in the side arm of the cannula. RESULTS: Coagulation of
      the communicating vessels was successful in all cases. The total number of
      fetuses who survived to delivery was 48 (53 percent), and the number of
      pregnancies with at least 1 survivor was 32 (71 percent). Among the live-born
      infants, the median gestational age at delivery was 35 weeks (range, 25 to 40),
      and the median birth weight was 2098 g (range, 550 to 4252). The median interval
      between the endoscopic laser procedure and delivery was 14 weeks (range, 0 to
      21). All the survivors were developing normally at a median age of 12 months
      (range, 2 to 24). CONCLUSIONS: Our preliminary experience suggests that the twin
      twin transfusion syndrome can be treated effectively by endoscopic laser
      coagulation of the communicating placental vessels.

PMID- 7808490
TI  - Images in clinical medicine. Human immunodeficiency virus.

PMID- 7808489
TI  - Brief report: absence of intact nef sequences in a long-term survivor with
      nonprogressive HIV-1 infection.

PMID- 7808491
TI  - Drugs and surgery in the prevention of ischemic stroke.
AB  - Randomized clinical trials have proved that warfarin therapy decreases the risk
      of stroke in patients with nonvalvular atrial fibrillation and in those who have
      had a myocardial infarction. In patients who are not candidates for long-term
      anticoagulant therapy, aspirin is beneficial, but the reduction in risk is
      smaller with aspirin than with warfarin. In patients with cerebral ischemic
      symptoms of noncardiac origin, aspirin and ticlopidine reduce the risk of stroke,
      but the benefit is modest. Given alone, neither dipyridamole nor sulfinpyrazone
      prevents stroke. The question remains whether either of these drugs plus aspirin
      is better than aspirin alone. The optimal dose of aspirin for stroke prevention
      has not been established. Carotid endarterectomy reduces the risk of stroke in
      symptomatic patients with at least 70 percent stenosis, as determined by
      arteriography. Current trials are addressing the question of whether
      endarterectomy is beneficial for patients with moderate degrees of carotid
      stenosis. The benefit of endarterectomy for patients with asymptomatic carotid
      lesions remains unclear.

PMID- 7808492
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 3-1995. A 29-year-old man with AIDS and multiple splenic
      abscesses.

PMID- 7808493
TI  - Lessons from people with nonprogressive HIV infection.

PMID- 7808494
TI  - Post-remission treatment of acute myelogenous leukemia.

PMID- 7808495
TI  - Institutional conflict of interest.

PMID- 7808496
TI  - Reducing the risk of falls among the elderly.

PMID- 7808497
TI  - Reducing the risk of falls among the elderly.

PMID- 7808498
TI  - Foot disease in diabetes.

PMID- 7808499
TI  - Foot disease in diabetes.

PMID- 7808500
TI  - Foot disease in diabetes.

PMID- 7808501
TI  - Deferoxamine in thalassemia major.

PMID- 7808502
TI  - Deferoxamine in thalassemia major.

PMID- 7808503
TI  - Deferoxamine in thalassemia major.

PMID- 7808504
TI  - Bronchiolitis obliterans with organizing pneumonia in AIDS.

PMID- 7808505
TI  - Enteroaggregative Escherichia coli as a possible cause of diarrhea in an HIV
      infected patient.

PMID- 7808506
TI  - The Eiken Latex test for detection of a cryptococcal antigen in cryptococcosis.
      Comparison with a monoclonal antibody-based latex agglutination test, Pastorex
      Cryptococcus.
AB  - A latex agglutination test for cryptococcal antigen, the Eiken Latex test (Eiken,
      Tokyo, Japan), was compared with a monoclonal antibody-based agglutination assay,
      Pastorex Cryptococcus (Diagnostics Pasteur, Marneur-la-Coquette, France). In a
      murine model of disseminated cryptococcosis, the kinetics of the antigen titers
      by the Eiken Latex were similar to those by the Pastorex Cryptococcus, but
      sensitivity was much higher. In HIV-negative patients with pulmonary
      cryptococcosis, a cryptococcal antigen was detected in 6 of 10 patients by the
      Eiken Latex test and in only 3 of those patients by the Pastorex Cryptococcus.
      The results indicate that the Eiken Latex is more sensitive for the detection of
      the cryptococcal antigen, even in non-disseminated cryptococcosis. The
      sensitivity and specificity of the Eiken Latex were examined using 195 sera from
      25 patients with pulmonary cryptococcosis and 170 patients with non
      cryptococcosis. The cutoff value of > or = 1:8 showed a sensitivity of 76%
      (19/25) and a specificity of 98.9% (168/170).

PMID- 7808507
TI  - Update of Penicillosis marneffei in Thailand. Review article.
AB  - Penicillium marneffei is endemic in Southeast Asia. Although Thailand is a
      country in this region, penicillosis marneffei was rare. It was found
      occasionally in immunocompromised patients. With the increasing incidence of HIV
      seropositivity penicillosis marneffei emerged as one of the major problems in HIV
      infected patients residing in Thailand. The common presenting signs were fever,
      anemia, hepatomegaly, lymphadenopathy. productive cough and a common skin
      manifestation as molluscum contagiosum-like lesions. The diseases should be
      considered in Thais and immunocompromised travelers with a history of visiting
      Thailand. Because the disease is potentially curable, prompt diagnosis and
      treatment will lead to better prognosis.

PMID- 7808509
TI  - Airborne fungal load in agricultural environment during threshing operations.
AB  - The effect of threshing operations on the fungal spora of farm air, has been
      studied with the culture plate method. Air samples were taken before, during and
      after the threshing of paddy and wheat grains, at the end of the respective crop
      seasons. An immediate local increase in the airborne fungal load was observed
      during threshing operations. In case of wheat the high rise was due to Alternaria
      tenuissima, followed by Drechslera sp. and Cladosporium herbarum. In 'Boro'
      variety of paddy, the high count was contributed by Alternaria humicola and A.
      tenuissima, while in 'Aman' variety, Helminthosporium oryzae was the dominant
      type followed by C. herbarum and unidentified yeasts. Aspergillus spp. were
      observed in significant numbers before the operation started; their occurrence
      was negligible during threshing. A considerable number of yeast was observed,
      particularly during threshing and after threshing operations.

PMID- 7808508
TI  - Neuroparacoccidioidomycosis: case reports and review.
AB  - Cerebral and cerebellar masses occurred in patients with paracoccidioidomycosis.
      Correct diagnosis was delayed due to overlooking the abnormal lung roentgenograms
      and the history of previous disease in a different localization. The fungus was
      identified through biopsy and direct examination of the samples. In two patients
      necropsy confirmed the diagnosis. None of the patients responded to amphotericin
      B or cotrimoxazole. A 10 year English and Latin American literature review on
      neuroparacoccidioidomycosis was performed through a MEDLINE and LILACS (Latin
      American Literature Search System) data base systems.

PMID- 7808510
TI  - A natural focus of Histoplasma capsulatum var. duboisii is a bat cave.
AB  - The natural reservoir of Histoplasma capsulatum var. duboisii, the etiological
      agent of histoplasmosis duboisii (African histoplasmosis) is not yet known. We
      report the isolation of H. capsulatum var. duboisii from soil admixed with bat
      guano and from the intestinal contents of a bat in a sandstone cave in a rural
      area, Ogbunike in Anambra State of Nigeria. Eight of 45 samples of soil admixed
      with bat guano yielded H. capsulatum var. duboisii. Of the 35 bats belonging to
      the species Nycteris hispida and Tadirida pumila examined, only one (N. hispida)
      yielded this fungus from its intestinal contents. Identification of the isolates
      as Histoplasma was confirmed by exoantigen tests and by mating with tester
      strains of H. capsulatum. In vitro conversion to large yeast from suggestive of
      H. capsulatum var. duboisii was obtained on brain heart infusion agar
      supplemented with sheep blood and glutamine or cysteine. Pathogenicity tests with
      mice for all the isolates confirmed their identity by the demonstration of large
      yeast forms (8-15 microns in diameter) within giant cells in the infected
      tissues. Investigations on the possible occurrence of human infections in the
      area are in progress.

PMID- 7808512
TI  - Mycoflora of the toxic feeds associated with equine leukoencephalomalacia (ELEM)
      outbreaks in Brazil.
AB  - The mycoflora of 39 feed samples associated with 29 Equine Leukoencephalomalacia
      (ELEM) outbreaks was studied from 1988 to 1990, in Brazil. Microbiological
      examination indicated Fusarium spp. as the most frequent mold which occurred in
      97.4% of samples followed by Penicillium spp. in 61.5% and Aspergillus spp. in
      35.9%. The moisture content of feed implicated in death of horses was above 15%
      which can favor the development of Fusarium spp. From the genus, F. moniliforme
      was the predominant species with an occurrence of 82.0%. Two additional species,
      not commonly associated with animal toxicosis, were isolated in low frequency, F.
      proliferatum (12.8%) and F. subglutinans (2.6%). It is important to emphasize
      that the isolation of F. proliferatum and F. subglutinans from feed obtained from
      the epizootic areas has not been documented previously in Brazil.

PMID- 7808511
TI  - Possible relationship of succinate dehydrogenase and fatty acid synthetase
      activities to Aspergillus parasiticus (NRRL 5139) growth and aflatoxin
      production.
AB  - Fatty acid synthetase (FAS) activity measured over time corresponded to aflatoxin
      B1 biosynthesis by Aspergillus parasiticus grown in minimal salts sucrose medium.
      Succinate dehydrogenase (SDH) activity, our primary metabolism indicator,
      decreased as FAS activity increased demonstrating that as primary metabolism
      slows, secondary metabolism and subsequently aflatoxin production begins. Fungal
      biomass, as measured by chitin, increased up to day 13 then stabilized. Calcium,
      potassium, magnesium, manganese, zinc, and a combination of these minerals were
      tested to determine their effect in culture on FAS and SDH activities. Cultures
      grown in broth supplemented with zinc had greater FAS activity and produced more
      aflatoxin B1 when compared to the unsupplemented control. To determine if enzyme
      activity in a complex substrate is altered due to mineral composition, peanuts
      were cultivated with gypsum (calcium sulfate) supplementation. The peanuts grown
      had higher calcium content but less zinc. All peanuts grown in gypsum treated
      fields had less aflatoxin produced on them when compared to unsupplemented
      peanuts. Also, FAS activity was lower and chitin content was less when compared
      to the unsupplemented control peanuts. The FAS activity observed in these
      experiments indirectly suggests that the FAS complex may be responsible for
      producing the precursor for aflatoxin synthesis. However, additional information
      is needed to validate this hypothesis.

PMID- 7808513
TI  - Disturbances in the production of interleukin-1 and tumor necrosis factor in
      disseminated murine sporotrichosis.
AB  - Production of Interleukin-1 (IL-1) and Tumor Necrosis Factor (TNF) by adherent
      peritoneal cells from BALB/c mice was measured at week 2, 4, 6, 8 and 10 after
      intravenous inoculation with 10(6) Sporothrix schenckii yeasts. As compared with
      age-matched controls, IL-1 and TNF production by adherent peritoneal cells from
      S. schenckii-infected mice was reduced severely at week 4 and 6 of infection and
      greater than normal at week 8 and 10. Moreover, between week 4 and 6 of infection
      there was a depression of delayed type hypersensitivity response to a specific
      whole soluble antigen, and an increase in fungal multiplication in the livers and
      spleens of infected mice. Thus, the deficits of cell-mediated immunity in mice
      with systemic S. schenckii infection may derive, in part, from impaired
      amplification of the immune response consequent to abnormal generation of IL-1
      and TNF.

PMID- 7808514
TI  - Treating HIV infection: a question of ethics.

PMID- 7808515
TI  - Treating HIV infection: a question of ethics.

PMID- 7808516
TI  - Domestic violence: a hard-line primer...

PMID- 7808517
TI  - How North Carolina laws affect the care of adolescents. Issues of confidentiality
      and consent.
AB  - The care of adolescent patients frequently presents clinicians with legal
      dilemmas. We have reviewed some of the relevant legal issues, but our comments
      are not intended to provide legal advice. Rather they are guidelines that may be
      helpful in these complex clinical situations. Readers should consult legal
      counsel for specific questions or concerns.

PMID- 7808518
TI  - Mandatory reporting of occupational health problems. A new surveillance program
      in North Carolina.

PMID- 7808519
TI  - A look at hypertension in North Carolina, 1991.

PMID- 7808521
TI  - A change in death registration. How to fill out the amended North Carolina death
      certificate.

PMID- 7808520
TI  - A new era: Alzheimer's is becoming manageable.

PMID- 7808522
TI  - Not all rats have four legs. Superwarfarin poisoning.

PMID- 7808523
TI  - Cystitis glandularis. Transition to adenocarcinoma of the urinary bladder.

PMID- 7808524
TI  - My involvement in the Iranian hostage crisis.

PMID- 7808525
TI  - [Headache caused by analgesics].

PMID- 7808526
TI  - [The seal finger; an infection due to contact with seals].

PMID- 7808527
TI  - [Spondylodiscitis cause by Brucella suis].
AB  - In a 72-year-old Dutchman Brucellae suis spondylodiscitis TXII-LI was diagnosed,
      complicated by a paraspinal abscess, for which surgical drainage was carried out.
      The patient failed to recover after the combined antibiotic regimen of
      doxycycline, rifampicin and trimethoprim-sulfamethoxazole. There was good
      clinical improvement after a course of doxycycline and streptomycin, however.
      After a symptom-free period of 9 weeks a relapse occurred. The patient refused
      treatment and died 6 weeks later at home. The infection had probably been
      contracted after handling wild boar carcasses from eastern Europe.

PMID- 7808528
TI  - [Rhodococcus equi pneumonia in patients with immunodeficiency].
AB  - In three patients, men of 30, 21 and 24 years old respectively, Rhodococcus equi
      pneumonia was diagnosed. Antibiotic treatment, followed by secondary prophylaxis,
      was successful. In one patient, lobectomy was done. R. equi, a well-known
      bacterial pathogen in horses, appears also to be pathogenic in humans in case of
      immunodeficiency.

PMID- 7808529
TI  - [A scorpion sting in The Netherlands].
AB  - A 16-year-old girl was stung in the Netherlands by a poisonous scorpion which had
      travelled in her suitcase from Turkey. Although she came to the emergency
      department immediately and had the (dead) scorpion with her, it proved to be
      extremely difficult to devise effective therapy quickly. There were only three
      ampoules of antiserum in the country, none of them against the scorpion
      concerned: Buthus gibbosus, a relatively dangerous species. Eventually, antiserum
      was flewn in from the Institut Pasteur near Paris, it was available 16 h after
      the patient came to the hospital. The antiserum was not used as the patient
      gradually recovered.

PMID- 7808530
TI  - [Boutonneuse fever caught in The Netherlands: a traveling dog as source of
      Rickettsia conorii].
AB  - In three patients, women aged 27, 26, and 36 years respectively, boutonneuse
      fever was suspected, although they had not recently visited an endemic area.
      Serological investigation confirmed the diagnosis. Treatment with doxycycline was
      effective. Circumstantial evidence strongly suggested that the infection with
      Rickettsia conorii had been transmitted through dogs that had stayed in
      Mediterranean countries and had carried ticks to the Netherlands.

PMID- 7808532
TI  - [Medical viewpoints on headache and migraine in The Netherlands; 16th-19th
      century].

PMID- 7808531
TI  - [With an eye on... the champagne cork].
AB  - Two patients, males of 31 and 15 years old, developed blunt injury of one eye,
      including hyphaema, due to a champagne cork. In one patient surgical evacuation
      was performed, the other recovered with drug therapy only. Inquiries in other
      ophthalmic departments in the Netherlands indicate that this type of trauma seems
      to be more frequent at the turn of the year.

PMID- 7808533
TI  - ['Contre la mort na medicine' ('There is no remedy for death'): the role of
      medicine in late-medieval danses macabres].

PMID- 7808534
TI  - [Stokvis and psychosomatics].

PMID- 7808535
TI  - [Rembrandt's Dr. Deijman's Anatomy Lesson].

PMID- 7808536
TI  - [Observations by Pieter van Foreest during the plague in Delft (1557-'58)].

PMID- 7808537
TI  - [Craniotomy; a ,much-alive tradition with the Kisii (Kenya)].
AB  - From 1981 until 1986 the authors witnessed traditional craniotomies being
      performed in the Kisii tribe in South West Kenya. The indication is the
      prevention or reduction of headache after trauma capitis. The frequency of the
      operation is estimated at 1 per 1000 persons a year. The aim is to remove part of
      the skull around the 'traumatic burst'. After shaving off the hair, the 'omobari
      omotwe' ('surgeon of the head') makes an incision at the place of the trauma or
      the headache. The bleeding is stopped with crushed leaves. With primitive
      instruments the bone is scraped away until the dura mater is reached, which is
      left untouched very carefully. The operation is carried out without anaesthesia,
      takes an average of 45 min and is sometimes completed by putting fat on the
      wound. A postoperative recovery period of 6-12 weeks is usual. The operation is
      highly regarded and seems to have few complications. Reoperations are frequent:
      one patient underwent the operation 26 times.

PMID- 7808538
TI  - [Belt and suspenders. Medical jargon in The Netherlands and Flanders].

PMID- 7808539
TI  - Reminiscences of Operation Restore Hope.

PMID- 7808540
TI  - A doctor remembers Somalia.

PMID- 7808541
TI  - Malaria field studies at NAMRU-2, Indonesia.

PMID- 7808542
TI  - Navy medicine March-April 1943.

PMID- 7808543
TI  - Disinfection of a sewage contaminated fresh water holding tank at a remote shore
      facility: potential for illness and injury.

PMID- 7808544
TI  - Reserve readiness researcher studies NRRC Detroit.

PMID- 7808545
TI  - Putting out the smoking lamp.

PMID- 7808546
TI  - Patient encounter skills development.

PMID- 7808547
TI  - The innocent flame of ignorance.

PMID- 7808548
TI  - Fly-away advanced care system.

PMID- 7808549
TI  - Charting a new course for Navy medical education.

PMID- 7808550
TI  - Innovations in alcoholism treatment.

PMID- 7808551
TI  - Assessment of the TQL infrastructure in Navy medicine.

PMID- 7808552
TI  - Health psychology in the Navy: emergence of a new discipline.

PMID- 7808553
TI  - A conversation with the Surgeon General.

PMID- 7808554
TI  - Navy medicine January-February 1944.

PMID- 7808556
TI  - Reserve dental exercise JOTS'93.

PMID- 7808555
TI  - Photorefractive surgery in the Navy.

PMID- 7808557
TI  - How to close a Naval Hospital.

PMID- 7808558
TI  - Strategic planning and TQL at Doctrine Center.

PMID- 7808560
TI  - Navy medicine March-April 1944.

PMID- 7808559
TI  - Malaria (part 1). Lessons from Somalia and General Slim.

PMID- 7808561
TI  - Approach to bleeding disorders.

PMID- 7808562
TI  - Learning survival at Naval Hospital Cherry Point.

PMID- 7808563
TI  - [Corticobasal degeneration. The significance of clinical criteria for
      establishing the diagnosis].
AB  - Neuropathological studies show that about 20% of all patients suffering from an
      acinetic-rigid syndrome can not be given the diagnosis of idiopathic Parkinson's
      disease. Among these non-idiopathic Parkinson-syndromes the corticobasal
      degeneration (CBD) can be regarded as a separate disease entity. The pathological
      findings of moderate predominantly frontal and parietal cerebral atrophy,
      cortical Pick-cells and specific corticobasal inclusion bodies are considered
      valuable features which support the diagnosis. The clinical Characteristics of
      CBD are demonstrated in 3 patients including an acinetic-rigid syndrome, limb
      apraxia and "alien limb"-syndrome, as well as reflex myoclonus. Eye movement
      disorders, dementia and other rare symptoms may also be present.
      Electrophysiological reflex-testing helps to corroborate diagnosis. These
      findings and a summary which includes the previously published cases of CBD show
      that CBD in most cases can be diagnosed intra vitam.

PMID- 7808564
TI  - [Stereotaxic radiosurgery].
AB  - Radiosurgery aims at the precise destruction of small, defined volumes of tissue
      by employing ionizing radiation energy. Its methodologies may be subdivided into
      closed-skull, external focussed beam radiosurgery, and interstitial radiosurgery
      (brachytherapy). Focussed beam stereotactic radiosurgery has been used
      successfully for over two decades to treat cerebral arteriovenous malformations.
      Complete obliteration ranges from 30% to 50% after one year. After two years,
      obliteration is observed in up to 90% of patients. Outcome, however, is
      influenced by patient selection. In the treatment of acoustic neurinomas, follow
      up data of larger series show that radiosurgery performed under local anesthesia
      on an out-patient basis is competitive with microsurgery data. Using multiple
      isocenters and magnetic resonance localization, tumor growth control is achieved
      in more than 90% of patients with preservation of hearing in approximately 50%.
      Pituitary tumors with Cushing's syndrome, acromegaly, Nelson's syndrome,
      prolactinomas and non-secreting adenomas have been treated. Only a small subgroup
      of patients with low-grade gliomas are candidates for interstitial radiosurgery,
      namely those with circumscribed tumors with limited spread of tumor cells into
      the periphery. For this subgroup, which usually comprises not more than 25% of
      all low-grade gliomas, interstitial radiosurgery competes with surgical
      resection. Local, single high-dose treatment remains controversial for highly
      malignant infiltrative tumors, and a significant treatment benefit remains to be
      demonstrated. Radiosurgery can be used to effectively treat solitary brain
      metastases (< or = 3 cm diameters) with less invasiveness, and dissection of
      normal tissue; it may be performed with lower morbidity and with less expense in
      comparison with open surgery.

PMID- 7808565
TI  - [Amitriptyline in therapy of chronic tension headache].
AB  - In a double-blind, placebo-controlled trial, the effect of 75 mg of a slow
      release formulation of amitriptyline on the clinical severity of chronic tension
      type headache and on headache-associated neurophysiological parameters (EMG
      activity, exteroceptive suppression of temporal muscle activity, contingent
      negative variation (CNV) and experimental pain sensitivity) was investigated. All
      of the patients treated had a history of headaches of many years standing, and
      numerous failed attempts at treatment. In the amitriptyline group, a significant
      reduction in daily headache duration was already found in the third week of
      treatment, while in the placebo group no significant changes in headache duration
      were to be seen. In week 6 the amitriptyline group had a significantly shorter
      daily duration of headache than the placebo group. Treatment did not result in
      any significant effects on EMG recording of pericranial muscle activity either
      during relaxation or contraction, on exteroceptive suppression of the temporal
      muscle and on CNV. The sensitivity to suprathreshold experimental pain, however,
      was significantly reduced. The data show a statistically relevant reduction of
      daily headache duration in chronic tension-type headache. However, they also show
      that amitriptyline can only partly alleviate chronic headaches but cannot cure
      them.

PMID- 7808566
TI  - [Psychiatric comorbidity in dissociative disorders in neurology].
AB  - We studied consecutively 50 neurologic inpatients of a university neurological
      department with dissociative (conversion) disorders with regard to their
      associated psychopathologic features as well as to their comorbidity. The study
      involved both self-measuring instruments and a standardized psychiatric
      interview. As a result patients with conversion disorders appeared as a
      psychopathologic highly disturbed group. We found that although the dissociative
      symptoms are phenomenological very predominant and were the reason for hospital
      admission in all cases, they must be interpreted as accompanying features in the
      context of complex psychiatric disorders. Diagnostic and therapeutic consequences
      are discussed with regard to the neurology.

PMID- 7808567
TI  - [Standardized analysis of visuospatial perception. Studies of objectivity,
      reliability and validity].
AB  - Retest reliability and validity of a computational method (VS, [19]) for the
      analysis of visual spatial perception in brain damaged patients was investigated.
      Retest reliability was tested in 20 patients (retest interval: 1 week; range: 1
      3) and varied from r = 0.65-0.95 for the different subtests for the "point of
      subjective equality" and r = 0.39-0.89 for the "interval of uncertainty". In the
      several investigations concerning the validity of VS. 234 patients and 10 normal
      subjects participated. In the first place, we found significant relationships of
      some of the subtests of VS to similar visual-spatial tests, but no relationship
      to tests of visual object perception. Secondly, we found significant
      relationships to certain tasks which approximated daily functioning. In summary,
      the present results demonstrate the objectivity, retest-reliability and validity
      of VS in brain damaged patients.

PMID- 7808568
TI  - [Presynaptic nigrostriatal function in Parkinson disease and Parkinson-plus
      syndromes. Comparative studies using positron emission tomography with L-6
      (18F)fluorodopa].
AB  - L-6-[18F]fluorodopa PET is suitable to assess the presynaptic nigrostriatal
      function within the living human brain. The purpose of this study was to compare
      the striatal rate constant Ki for L-6-[18F]fluorodopa in patients with
      Parkinson's disease (PD), Parkinsonism plus syndromes (PPLUS) and controls. 27
      patients (m: 13, f: 14) between 36 and 75 years and 20 controls (m: 10, f: 10)
      between 20 and 85 years were examined. The clinical severity of the akinesia and
      rigidity were rated on the modified Columbia scale. In patients with PD the mean
      value of Ki was determined to be 0.339 +/- 0.098 [ml/striatum/min], in PPLUS
      0.161 +/- 0.083, and in controls 0.708 +/- 0.121. The values of Ki were
      significantly different among the three groups (P = 0.001, ANOVA). The side-to
      side difference D % of Ki was calculated to be 9.1% +/- 6.8% in PD, 14.2% +/-
      10.9% in PPLUS, and 5.1% +/- 5.5% in controls (P = 0.079 PD vs. controls, 0.172
      PD vs. PPLUS, and P = 0.003 PPLUS vs. controls). Ki values and rating on the
      Columbia scale did not show a strong correlation in both PD and PPLUS. In
      conclusion, the presynaptic nigrostriatal function seems to be more affected in
      PPLUS compared with PD. These findings may support the hypothesis of a "levelling
      off" of the dopaminergic function in PD.

PMID- 7808570
TI  - [Dural arteriovenous fistula as a rare cause of intracerebral hemorrhage].
AB  - Dural arteriovenous fistulas are rare vascular malformations presenting with very
      different clinical signs, depending on the pattern of venous drainage. Retrograde
      leptomeningeal venous drainage is significantly correlated with a progressive
      neurological presentation. A case of a dural arteriovenous fistula with cortical
      venous drainage is presented. The draining vein was frankly aneurysmal dilated.
      Rupture of this venous aneurysm caused an intracerebral hemorrhage. The venous
      varix and the hematoma were microsurgically resected and evacuated.

PMID- 7808569
TI  - [Variants of Todd's paralysis: postictal apraxia and prolonged postictal
      hemineglect].
AB  - Todd's post-epileptic paralysis is a well-known complication after focal or
      generalized epileptic seizures. The underlying pathophysiology, however, is still
      unknown. Commonly, it is associated with a hemiparesis, usually lasting minutes
      or hours, rarely as long as two days, with subsequent complete remission. We
      report 2 patients with unusual and variant post-epileptic syndromes which have
      not been previously described in the literature: first, an ideomotor limb
      apraxia, and second, a severe hemineglect syndrome. Each syndrome lasted up to 70
      hours after the seizure and was completely reversible.

PMID- 7808571
TI  - [Symptomatic acoustic hallucinations after traumatic brain damage. Review of the
      literature and case report].
AB  - Symptomatic hallucinosis can be observed after subcortical lesions of different
      localisation with a predominance of complex-visual perceptive disturbances. Only
      single cases with complex acoustic hallucinosis have been reported in the
      literature. A 30-year-old patient is presented who suffered from a midbrain
      syndrome after severe traumatic brain injury and developed an acoustic
      hallucinosis in the chronic stage of rehabilitation. The functional relevance and
      therapeutic strategies are considered with regard to the relevant literature.

PMID- 7808572
TI  - [Stiff-man syndrome. Report of 4 cases].
AB  - Four patients are presented who exhibited progressive muscular rigidity in both
      legs, the thoracolumbar, paraspinal and the abdominal muscles. In only one
      patient, there was an initial involvement of the shoulder girdle muscles.
      Electromyography in all four patients at rest recorded continuous electric
      activity resembling an interference pattern. Following sudden exteroceptive
      stimuli the activity increased in amplitude and density this corresponded
      clinically to painful spasms. All patients had oligoclonal banding in CSF. In the
      serum and CSF of three patients IgG subtype autoantibodies were detected. These
      have been found to be directed against GABAergic nerve terminals in the rat and
      human cerebellum and, more specifically, to glutamic acid decarboxylase. All
      patients improved on clonazepam. Trials of intermittent high-dose
      methylprednisolone administration gave relief from rigidity in one patient and
      permitted reduction of clonazepam in another. Intravenous immunoglobulins however
      had no effect in one patient.

PMID- 7808573
TI  - [Rhabdomyolysis in neuroleptic therapy: an abortive malignant neuroleptic
      syndrome?].
AB  - We report on the case of a 24 year old female patient, who, at first developed
      during 8 weeks of neuroleptic therapy parkinsonism and then, after improvement of
      psychopathology an acute rhabdomyolysis. Hyper-Ck-aemia up to 11,340 U/l was
      observed. Laboratory parameters normalized shortly after neuroleptics had been
      withdrawn and no further complications followed. Symptomatology is discussed with
      special reference to the possibility of an abortive malignant neuroleptic
      syndrome.

PMID- 7808575
TI  - Farewell to "CARA"?

PMID- 7808574
TI  - [Recurrent pneumococcal meningitis after splenectomy].
AB  - We report the case of a female patient with thrombocytopenic purpura Werlhof.
      Splenectomy was followed by relapsing pneumococcal meningitis. Particularly,
      repetitive infections were caused by pneumococcus capsula type 13. This type is
      not included in the common 23-polyvalent vaccine matter. The necessity of
      splenectomy in autoimmunological diseases should be considered carefully in the
      individual case. Patients should be well informed of the high risk of infection
      after splenectomy and should undergo medical treatment immediately.

PMID- 7808576
TI  - Does bronchial hyperresponsiveness precede or follow airway obstruction in asthma
      or COPD?
AB  - OBJECTIVE: The following hypothesis was tested: The degree of bronchial
      hyperresponsiveness (BHR) is a risk factor for the progression of airway
      obstruction in asthma, while in chronic obstructive pulmonary disease (COPD) it
      reflects the existing airway obstruction. METHODS: The relationships between the
      (annual change in) PC20 histamine and the (annual change in) FEV1 were
      investigated in a 2-year prospective controlled study. The FEV1 and the PC20
      histamine were assessed at 6-month intervals. 183 patients (74 asthma, 109 COPD)
      participated. The investigated relationships were assessed by means of multiple
      analysis of variance (ANOVA). Patients used bronchodilator therapy alone. No
      steroids were permitted during the study. RESULTS: The results demonstrated that
      the PC20 at the start of the study was related to the subsequent annual decline
      of FEV1 in asthma (r = 0.32, p < 0.05) but not in COPD (r = -0.10, p = 0.89).
      Asthmatic patients with a PC20 value < or = 2 mg/ml had an average decline of 118
      ml/yr, those with a PC20 value > 2 mg/ml of 27 ml/yr. The change in PC20
      histamine during the 2-year study period was related to the annual change in FEV1
      in COPD (r = 0.45, p < 0.05), but not in asthma (r = 0.06, p = 0.90). The
      disturbing influence of possible confounders was investigated and if necessary
      controlled for. CONCLUSIONS: It was concluded that BHR, assessed with PC20
      histamine, is probably involved in the progression of airway obstruction in
      asthma. In COPD, however, the degree of BHR probably only reflects the degree of
      existing airway obstruction. This conclusion may contribute to the ongoing debate
      whether it is useful to combine the diagnosis of asthma, COPD and emphysema under
      the umbrella-term CARA (or CNSLD = chronic non-specific lung disease). The so
      called "Dutch hypothesis" which laid the foundation for this term, suggested that
      bronchial hyperresponsiveness plays a central role in the pathogenesis of CNSLD.
      The present study supports evidence that at least BHR does not seem to play the
      same role in the pathogenesis of asthma and COPD.

PMID- 7808578
TI  - Rounded atelectasis of the lung, just a benign disorder.
AB  - Three patients with rounded atelectases are described. One of them developed a
      malignant non-Hodgkin lymphoma 6 months after presentation with rounded
      atelectasis. His rounded atelectasis could be followed during 20 months and was
      unrelated to the appearance, complete remission after chemotherapy and relapse of
      a malignant non-Hodgkin lymphoma. Rounded atelectasis of the lung is a little
      known form of peripheral pulmonary collapse which may mimic a neoplastic tumour.
      It might be formed either because of a folding in a basal lung segment caused by
      temporarily pleural effusion, or because of initial damage to the pleura which
      leads to fibrosis and thus to challenge to the clinician, it should be emphasized
      that the benign nature of rounded atelectasis should be recognized by
      radiological techniques.

PMID- 7808577
TI  - Pulmonary rehabilitation at moderate altitude: a 1-year follow-up.
AB  - BACKGROUND: In order to evaluate a pulmonary rehabilitation program (PRP) at
      moderate altitude (1560 m) 62 patients with obstructive lung disease were asked
      to participate; 37 patients completed a 1-year follow-up at sea level, and 25
      patients dropped out. The exercise training program lasted for 10 weeks and
      consisted of a cycling and running program of 20 min daily, 5 days a week.
      METHODS: Incremental exercise testing, spirometry and histamine provocation tests
      were performed at sea level before the PRP, on admission to the Dutch Asthma
      Centre, Davos, after 5 weeks of exercise training, at discharge from the Centre
      and 6 and 12 months after discharge at sea level. RESULTS: The PRP led to an
      increase in exercise capacity of the 37 patients who also completed the follow-up
      as reflected by an increase in Wmax (from 104 +/- 44 watt on admission to 150 +/-
      8 at discharge, p < 0.001). HRmax (145 +/- 19/min to 151 +/- 21, p < 0.001),
      Wmax/HR (0.71 +/- 0.26 watt/beat/min to 0.99 +/- 0.29, p < 0.001), VO2max (1.4 +/
      0.4 l/min to 1.9 +/- 0.6, p < 0.001) and VEmax (49 +/- 18 l/min to 78 +/- 24, p
      < 0.001) measured at discharge from the Dutch Asthma Centre after the PRP were
      significantly higher than before the PRP at incremental exercise testing. The
      group of 25 patients who dropped out showed corresponding improvements in these
      parameters after the PRP in Davos. The 37 patients who completed the follow-up
      showed at incremental exercise testing 1 year after the PRP that only two of
      these parameters were still significantly elevated: VO2max 1.8 +/- 0.6 (p <
      0.001) and VEmax 61 +/- 21 (p < 0.001). One year after the PRP arterial PCO2
      values at maximum exercise were significantly lower (5.2 +/- 0.8 kPa, p < 0.05)
      than the baseline values (5.5 +/- 0.9 kPa). CONCLUSIONS: PRP at moderate altitude
      results in an increase of exercise tolerance in patients with asthma or COPD, but
      significant long-term effects are few.

PMID- 7808580
TI  - Unusual presentation of acquired toxoplasmosis in an immunocompetent adult.
AB  - We report an unusual clinical presentation of toxoplasmosis. Fever and headache
      were the only complaints of a 48-year-old immunocompetent man who was found to
      have a rash, hepatitis and a pericardial effusion. Lymphadenopathy was not
      present. Evolving atypical lymphocytosis was the clue to the diagnosis of
      toxoplasmosis. Undercooked meat was the probable source of infection.

PMID- 7808579
TI  - Acute thyroiditis caused by Moraxella nonliquefaciens.
AB  - A 43-year-old woman presented with thyroiditis caused by Moraxella
      nonliquefaciens. Antibiotic therapy resulted in complete recovery. The literature
      on M. nonliquefaciens and acute bacterial thyroiditis is reviewed. This is the
      first documented case of a thyroiditis caused by M. nonliquefaciens.

PMID- 7808581
TI  - Extraskeletal localization of 99mTc-labeled bone-seeking tracers in bone
      scintigraphy.
AB  - In this article clinical examples of extraskeletal localization of technetium-99m
      (99mTc)-labeled diphosphonate are described. In several of these cases this
      finding was relevant for clinical decision-making. 99mTc-labeled diphosphonates
      have been used for skeletal imaging since 1971, and from 1973 on many reports of
      extraskeletal localizations of these agents have been published. This
      visualization can be due to (1) an abnormality of the excretory route of 99mTc
      labeled diphosphonate or (2) increased uptake in pathologically altered tissues
      and organs. The latter has been recorded in a multitude of disease processes,
      such as ischaemic injury, inflammatory processes, benign or malignant neoplasms,
      non-skeletal metastases, malignant pleuritis, scars, radiation injury and
      amyloidosis. Although the precise mechanism of extraskeletal uptake of 99mTc
      labeled diphosphonate remains uncertain, binding of this radiopharmaceutical to
      calcium-containing compounds is thought to play a critical role.

PMID- 7808582
TI  - Dorothy Russell Memorial Lecture. The molecular pathology of Alzheimer's disease:
      are we any closer to understanding the neurodegenerative process?
AB  - Alzheimer's disease, the most common cause of dementia in the elderly, is rapidly
      becoming epidemic in the western world, with major social and economic
      ramifications. Thus enormous international scientific efforts are being made to
      increase our understanding of the pathogenesis of this disease, with the eventual
      goal of developing beneficial therapy. The two major neuropathological hallmarks
      of Alzheimer's disease (AD) are extracellular senile plaques, the principal
      component of which is the A beta amyloid peptide, and intraneuronal
      neurofibrillary tangles, which are composed of aggregated tau protein in the form
      of paired helical filaments (PHF). In the past decade, since the major
      proteinaceous components of these pathological markers have been identified,
      great strides have been made in elucidating the biochemical processes which may
      underlie their abnormal deposition and aggregation in Alzheimer's disease.
      Simultaneously, extensive population genetic analyses have identified mutations
      in the A beta amyloid precursor protein (APP) in a small number of pedigrees with
      familial Alzheimer's disease (FAD) whilst other FAD cases have been linked to an,
      as yet, unidentified marker on chromosome 14. Most recently, inheritance of the
      type 4 allele of apolipoprotein E has also been identified as a risk factor in
      sporadic AD. The challenge facing scientists now is to incorporate this wealth of
      exciting new biochemical and genetic data into a coherent model which can explain
      the long established neurochemical and histopathological lesions characteristic
      of AD.

PMID- 7808583
TI  - Defining the limits of prion disease.
AB  - The term prion disease applies to any disease in which there is an accumulation
      in brain of the abnormal isoform of prion protein, known as PrPsc. These diseases
      include all the transmissible spongiform encephalopathies of humans and animals
      and their related atypical forms. Although there are clear clinical and
      neuropathological indicators in the majority of cases, the atypical forms present
      particular diagnostic difficulties because their clinical presentation may
      closely resemble much more common forms of dementia. On pathological examination
      the brain may show no spongiform encephalopathy, and attempts at transmission are
      often not successful in these cases. There are various biochemical and
      immunohistochemical ways in which prion disease can be detected. Some of these
      require the use of fresh/frozen tissue which is often not available unless prion
      disease is already suspected. Some previously unsuspected cases have been
      detected by genetic analysis of the PrP gene. This approach must be used with
      caution since there are several rare polymorphisms in the PrP gene which are not
      pathogenic and possession of a pathogenic mutation does not prevent the
      occurrence of more common neurological disorders at an earlier age, some of which
      may be treatable.

PMID- 7808584
TI  - The molecular genetics of schizophrenia.
AB  - There is strong evidence for a genetic component in schizophrenia but its precise
      nature remains unclear. Positional cloning and studies of potential candidate
      genes offer prospects for progress. The diagnosis of schizophrenia can now be
      made reliably but questions remain over the most valid phenotypic definition. To
      deal with this and uncertainties regarding mode of transmission a
      'polydiagnostic' approach is advisable. A wealth of new DNA markers has enhanced
      the potential for linkage studies which have so far focused on large multiply
      affected families. Multi-centre collaborative studies that are currently under
      way are likely to identify genes of major effect but other strategies are
      required if it turns out that most cases result from the combined effect of
      multiple genes.

PMID- 7808585
TI  - Analysing brain function and dysfunction in transgenic animals.
AB  - Many neuropsychiatric disorders have a genetic aetiology. In vivo gene
      modification offers a route to simulating such disorders in transgenic animals,
      allowing a systematic study of the underlying pathophysiology. However, attempts
      to mimic diseases such as Alzheimer's disease in transgenic animals have not yet
      been successful. This principally reflects our lack of knowledge concerning
      normal brain function, and an understanding of the biochemical mechanisms
      underlying cognitive processes is a primary objective. We and others have
      therefore focused on the hippocampus, a brain region involved in learning and
      memory and an early target for degeneration in Alzheimer's disease. Genetic
      intervention to date has yielded transgenic animals with apparent functional
      deficits in the hippocampus, leading the way to a greater understanding of brain
      function.

PMID- 7808586
TI  - Expression of utrophin (dystrophin-related protein) during regeneration and
      maturation of skeletal muscle in canine X-linked muscular dystrophy.
AB  - The regulation of utrophin, the autosomal homologue of dystrophin, has been
      studied in the canine X-linked model of Duchenne muscular dystrophy. Dystrophic
      muscle has been shown to exhibit abnormal sarcolemmal expression of utrophin, in
      addition to the normal expression at the neuromuscular junction, in peripheral
      nerves, vascular tissues and regenerating fibres. To establish whether this
      abnormal presence of utrophin in dystrophic muscle is a consequence of continued
      expression following regeneration, or is attributable to a disease related up
      regulation, the expression of utrophin was compared immunocytochemically with
      that of dystrophin, beta-spectrin and neonatal myosin in regenerating normal and
      dystrophic canine muscle, following necrosis induced by the injection of venom
      from the snake Notechis iscutatis. In normal regenerating muscle, sarcolemmal
      utrophin and dystrophin were detected concomitantly from 2-3 d post-injection,
      prior to the expression of beta-spectrin. Down-regulation of utrophin was
      apparent in some fibres from 7 d, and it was no longer present on the extra
      junctional sarcolemma by 14 d. Neonatal myosin was still present in all fibres at
      this stage, but dystrophin and beta-spectrin had been fully restored. In
      dystrophic regenerating muscle, down-regulation of utrophin occurred from 7 d,
      although it persisted on some fibres until 28 d, longer than in normal muscle. At
      42 d, however, utrophin in dystrophic muscle was only detected in a population of
      small fibres thought to represent a second cycle of regeneration, with no
      immunolabelling of mature fibres.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7808587
TI  - A molecular and cellular model to explain the differences in reactivation from
      latency by herpes simplex and varicella-zoster viruses.
AB  - There are marked similarities in the biological properties of the human
      neurotropic herpesviruses herpes simplex virus type 1 (HSV-1) and varicella
      zoster virus (VZV), including their ability to establish lifelong latent
      infections in human peripheral sensory ganglia (PSG). Despite this, their
      patterns of reactivation are quite different: HSV-1 reactivations occur many
      times during a lifetime, they are localized to the cutaneous distribution of a
      single sensory nerve, they are not associated with sensory symptomatology and
      their frequency decreases with age. VZV recurrence on the other hand is usually a
      single event which tends to appear with advancing age, its cutaneous eruption
      involves an entire dermatome and is usually extremely painful. To help explain
      these differences, we have formulated a model based on current knowledge of the
      molecular and cellular basis of latent infection in the nervous system. We
      suggest that the amount of latent viral DNA and RNA in the latently infected
      tissue (higher with HSV-1), the cellular location of latent virus (neuronal in
      HSV-1, probably non-neuronal in VZV), the presence or absence of viral
      replication in the PSG during reactivation together with the host immune
      response, are all key determinants of the clinical expression of viral
      reactivation.

PMID- 7808588
TI  - Prion protein immunocytochemistry: reliable protocols for the investigation of
      Creutzfeldt-Jakob disease.
AB  - Current criteria for the histological diagnosis of Creutzfeldt-Jakob disease
      (CJD) include features such as spongiform change, neuronal loss and reactive
      gliosis which are shared to a varying extent with other neuro-degenerative
      disorders. Reliable visualization of prion protein (PrP) has substantial
      potential value in diagnostic practice and as a research tool, since accumulation
      of the disease-associated isoform of this protein is apparently specific for
      spongiform encephalopathies. A number of antisera against PrP have previously
      been employed in conjunction with a range of pre-treatments designed to optimize
      the specificity of immunostaining; such varied usage makes the comparison and
      interpretation of results difficult. This study was undertaken to identify
      optimal combinations of each of three PrP antisera and five pre-treatments
      designed to specifically demonstrate disease-specific PrP in a series of seven
      CJD cases, six cases of Alzheimer-type dementia and six non-demented control
      cases. Specific staining of amyloid plaques, spongiform neuropil, neurons and,
      occasionally, astrocytes was achieved in CJD cases. Alzheimer and control cases
      were unstained. Use of formic acid with guanidine thiocyanate, and hydrolytic
      autoclaving with IB3 and SP30 antisera proved most effective and can be
      recommended for future immunocytochemical studies. PrP immunocytochemistry
      revealed a greater extent of subcortical neural involvement than routine
      histological techniques in CJD; the relationship between classical neuropathology
      in CJD and PrP accumulation as revealed by immunocytochemistry is not clear cut
      and requires further investigation. These findings may help to broaden our
      understanding of human spongiform encephalopathies, and have implications for
      diagnostic practices in neuropathology.

PMID- 7808589
TI  - Lewis rat EAN is suppressed by the 21-aminosteroid tirilazad mesylate (U-74006F).
AB  - Lewis rat experimental allergic neuritis (EAN) was treated with the 21
      aminosteroid, tirilazad mesylate (U-74006F). High doses of tirilazad mesylate,
      begun just before the onset of clinical signs, reduced the clinical and
      pathological severity of the disease. In rats immunized with a high dose of
      myelin, axonal degeneration was a major pathological feature. Tirilazad mesylate
      reduced the amount of axonal degeneration but had little effect on the other
      pathological features of EAN, such as inflammation and demyelination. Tirilazad
      mesylate may block axonal degeneration by inhibiting lipid peroxidation of axonal
      membranes. Inhibition of axonal degeneration is an important goal in the
      treatment of human neuropathies.

PMID- 7808590
TI  - MHC class II expression by microglia in tetanus toxin-induced experimental
      epilepsy in the rat.
AB  - Minute amounts of tetanus toxin injected into the hippocampus of rats results in
      an epileptiform syndrome. When the toxin injection is made unilaterally or
      bilaterally into the ventral hippocampus, about one-third of animals with
      seizures show bilateral neuronal loss in dorsal CA1 of the hippocampus after 1
      week. In animals with seizures, microglia in hippocampus are found to be
      activated. The present work shows that during the acute phase, microglia in the
      substantia nigra become activated and express MHC class II antigens in the
      majority of animals with seizures. After the animals have recovered from the
      acute phase at 8 weeks, the MHC class II expression has largely disappeared from
      the substantia nigra but MHC class II-expressing microglia are found in the
      dorsal hippocampus of those rats with loss of cells from CA1. These results show
      that microglia are responsive to abnormal electrical activity in the central
      nervous system in the absence of degenerative changes. Further studies are
      required to determine how microglia may contribute to the neuropathology of
      epilepsy.

PMID- 7808591
TI  - CR3/43, a marker for activated human microglia: application to diagnostic
      neuropathology.

PMID- 7808592
TI  - Current bibliographies of neuropeptides prepared by the University of Sheffield
      Biomedical Information Service.

PMID- 7808593
TI  - CCKB receptor signaling in rat pituitary GH3 cells. CCK-8S-induced intracellular
      calcium mobilization by Ca2+ release and Ca2+ influx.
AB  - We describe the effect of sulphated cholecystokinin octapeptide (CCK-8S) on
      [Ca2+]i in rat pituitary GH3 cells. Investigations were performed on fluo-3
      loaded cells by using a confocal imaging system MRC-600 (Bio-Rad). Because CCK-8S
      mobilized intracellular calcium in cells bathed in Ca(2+)-free buffer it must be
      able to release calcium from internal stores. Furthermore, influx of Ca2+ from
      outside the cells seems to contribute to CCK-8S induced increases in [Ca2+]i as
      demonstrated by calcium mobilization in GH3 cells preincubated with thapsigargin
      in Ca2+ containing buffer.

PMID- 7808594
TI  - Thyrotropin-releasing hormone: inhibitory function on growth hormone through both
      somatostatin and growth hormone-releasing factor neurons.
AB  - Double labelling immunohistochemistry using antibodies to thyrotropin releasing
      hormone (TRH) and somatostatin (SS) was undertaken in the anterior hypothalamus
      in 6 rats. Light microscopic quantitation revealed that 94.5% of SS
      immunopositive perikarya in the preoptic anterior hypothalamic area (PO/AHA) and
      97.5% in the paraventricular nucleus appeared to be contacted by one or more TRH
      immunopositive terminals. In the chronically cannulated unanaesthetised male rat,
      unilateral microinjections of a range of doses of TRH were made in the PO/AHA,
      where SS neurons are located, or in the medial basal hypothalamus, where growth
      hormone (GH)-releasing factor (GRF) neurons are located. Transient reductions in
      GH plasma levels occurred only after injections of the highest (10 nmol) dose of
      TRH in both sites. The function of TRH inputs to both somatostatin and GRF
      neurons appears to be inhibitory for GH. The physiological conditions in which
      these inputs function remain to be defined.

PMID- 7808595
TI  - Extrahypothalamic distribution of vasoactive intestinal polypeptide (VIP)-like
      immunoreactivity in the chicken brain, Gallus domesticus.
AB  - The distribution of VIP-immunoreactive neurons and fibers was detected in the
      extrahypothalamic areas of chicken brain by immunohistochemistry and light
      microscopy VIP-ir perikarya were found in the hippocampus and in the area
      parahippocampalis; in the area ventralis of Tsai, in the n. interpeduncularis, in
      the substantia nigra, in the substantia grisea centralis, in the locus coeruleus,
      in the n. subcoeruleus ventralis and in the n. pontis lateralis. VIP-ir fibers
      were seen in the lobus parolfactorius and throughout the brainstem mainly
      arranged in lateral and midsagittal position. This finding was discussed in
      relation to other studies performed on chicken and/or other avian brain. The
      distributional pattern of VIP-ergic system in the chicken brain suggests a
      possible involvement of VIP or VIP-like peptide in several neuroregulatory
      mechanisms.

PMID- 7808596
TI  - Prohormone convertases PC2 and PC3 in rat neutrophils and macrophages. Parallel
      changes with proenkephalin-derived peptides induced by LPS in vivo.
AB  - Prohormone- or proneuropeptide-converting enzymes PC2 and PC3 have been observed
      exclusively in nervous and endocrine tissues. In this work the presence of these
      enzymes in cells of the immune system was demonstrated. PC2 was detected in
      peripheral and liver-infiltrating polymorphonuclear leukocytes (PMN) but not in
      alveolar macrophages (AM) or spleen mononuclear cells (SMC). PC2 proteins
      corresponded to 75, 71 and 56 kDa forms. PC3 appeared in AM and SMC but not in
      PMN, and a 66 kDa protein was the only PC3 form detected. Proenkephalin-derived
      peptides (PENKp) were observed in PMN and AM, showing peptides of 35, 28, 21, 18
      and 14 kDa in the former cells and a doublet of 35 and 32 kDa in the latter. PC2
      proteins and PENKp decreased in liver PMN and peripheral PMN 90 min after
      intravenous (i.v.) infusion of LPS, suggesting an increased release. However, in
      vitro assays showed that the chemotactic peptide FMLP but not LPS increased the
      basal secretion of PC2 proteins and PENKp in PMN. These results indicate that PC2
      proteins are released from PMN, together with PENKp, and suggest that LPS in vivo
      may act through an indirect mechanism. Low levels of PC3 and PENK were detected
      in the AM of rats treated for 90 min with SAL or LPS. However, a significant
      increase of PC3 and PENKp appeared 30 h after LPS infusion. These results show
      for the first time that PC2 and PC3 are differentially expressed in PMN and AM,
      respectively, which were paralleled by the presence of different post
      translational products of PENK. In addition, the in vivo effect of LPS on PC2,
      PC3 and PENKp levels in PMN and AM resembles the effect of LPS on prohormone
      levels in endocrine tissues, suggesting that similar mechanisms may control the
      turnover of PENK in endocrine and in these immune cells.

PMID- 7808597
TI  - Oxytocin enhances, and oxytocin antagonism decreases, sexual receptivity in
      intact female rats.
AB  - In intact, non-ovariectomized female rats in spontaneous behavioral estrus, the
      i.c.v. injection of oxytocin significantly increased lordosis quotient and
      lordosis duration, starting from a dose of 1 ng/rat. On the other hand, the
      oxytocin antagonist, d(CH2)5Tyr(Me)-[Orn]8-vasotocin, injected at the same doses
      and by the same route, decreased lordosis quotient and lordosis duration, and
      prevented the effect of oxytocin. These data further support the notion that
      oxytocin plays a physiological role in female sexual receptivity.

PMID- 7808598
TI  - Insulin treatment stimulates the rat melanin-concentrating hormone-producing
      neurons.
AB  - Melanin-concentrating hormone (MCH) is involved in the regulation of body colour
      in teleost fish. A peptide highly homologous to salmon MCH has been found in the
      rat brain, but its physiological functions have not yet been precisely defined.
      The location of MCH neurons in the lateral hypothalamus (LHT) of the rat suggests
      possible implication in feeding behaviour. In the present study,
      immunohistochemical and in situ hybridization methods were used to investigate
      MCH gene expression following insulin injections. Five hours after insulin
      injection, a significant increase in the abundance and staining intensity of MCH
      immunoreactive perikarya and fibres was observed. Concurrently the level of MCH
      mRNA significantly increased (50%). Insulin-treatment also induced a marked and
      progressive increase in the number and staining intensity of nuclei detected by a
      Fos antiserum in LHT and other brain areas. Double labelling technique
      demonstrated that very few if any MCH neurons exhibited Fos-like
      immunoreactivity. These results demonstrate that an insulin-treatment stimulates
      MCH neuron activity without the mediation of the proto-oncogene c-fos. The
      mechanisms triggering this activation remain to be elucidated.

PMID- 7808599
TI  - Arteriovenous malformations in elderly patients.
AB  - This article discusses the presentation, natural history, and management of
      arteriovenous malformations (AVMs) in elderly patients, based on our experience
      at the Dartmouth-Hitchcock Medical Center. We also present a review of the
      literature. In our series of 50 patients with AVMs who were operated on by one
      surgeon, six patients were 65 years old or older at the time of presentation. All
      six patients presented with intracerebral hemorrhage, and one patient had
      developed a seizure disorder 2 months before hemorrhaging. In three patients, the
      clinical course was consistent with the occurrence of two hemorrhages within a 48
      hour period. The patients' preoperative neurological status varied from intact to
      moribund. In two patients, the diagnosis of AVM was made intraoperatively.
      Preoperative angiography revealed the diagnosis in the remaining patients. All
      the patients underwent surgical excision of their AVMs. Despite concurrent
      medical illnesses, all patients tolerated the procedure well with no new,
      persistent neurological deficits. At follow-up, all patients showed sufficient
      neurological recovery to return to the community and four of the patients were
      neurologically intact. Based on this experience and a review of the literature,
      we conclude that AVMs in elderly patients are not benign lesions and that
      surgical excision should be considered among the management options for these
      patients.

PMID- 7808600
TI  - Stereotactic magnetic resonance angiography for targeting in arteriovenous
      malformation radiosurgery.
AB  - Because conventional stereotactic angiography provides only two-dimensional
      information for dose planning, we studied the accuracy and usefulness of
      stereotactic magnetic resonance angiography (sMRA) for arteriovenous malformation
      (AVM) radiosurgery in 28 consecutive patients. We hypothesized that the
      multidimensional data set provided by sMRA and the opportunity to image both
      blood vessels and brain parenchyma would improve the accuracy of AVM irradiation
      and improve the safety of radiosurgery. Twenty-eight patients with AVMs in
      different brain locations and with a variety of AVM sizes (range, 15-31 mm mean
      diameter) had sMRA followed by stereotactic angiography. The sMRA images only
      were used to construct an initial radiosurgical plan. This plan was then used to
      outline the AVM volume defined by conventional angiography. In 24 patients, sMRA
      information equaled that of conventional angiography. In 3 patients, sMRA was
      better, because conventional angiography overestimated the size of the AVM nidus.
      In one patient, the conventional angiogram showed a second separate nidus (10-mm
      diameter) that was not as well defined on MRA. There were no complications with
      any procedure. In 16 patients (57%), sMRA provided critical information on AVM
      shape that was not provided by conventional angiography alone. Stereotactic MRA
      is a fast, noninvasive, inexpensive, multidimensional imaging method for AVM
      radiosurgery that provides information on vascular and parenchymal brain anatomy
      important for optimal dose planning. We believe that it can be used with
      confidence as the sole imaging method for medium-size, compact-nidus AVMs.

PMID- 7808601
TI  - Liver dysfunction in spontaneous intracerebral hemorrhage.
AB  - The purpose of this study was to investigate the relationship between mild
      degrees of liver dysfunction and spontaneous intracerebral hemorrhage (ICH) from
      the hemostatic standpoint. A detailed study of hemostatic systems was made in 462
      patients with ICH. To compare ICH with the other cerebrovascular diseases, data
      from 120 patients with subarachnoid hemorrhage and 114 others with cerebral
      infarction were reviewed. At admission, the medical histories of the patients,
      including information about previous alcohol consumption, was taken, and blood
      samples were collected to perform the following studies: platelet count,
      fibrinogen level, prothrombin time, activated partial thromboplastin time,
      antithrombin III, plasminogen and alpha 2-antiplasmin activity, platelet
      aggregability, and liver function tests. The incidence of liver dysfunction and
      alcohol consumption in patients with ICH was significantly (P < 0.05) higher than
      in patients with subarachnoid hemorrhage and in those with cerebral infarction.
      Hematoma volume, mortality rate, and past alcohol consumption in patients with
      ICH significantly increased with worsening severity of liver dysfunction.
      Although almost all hemostatic parameters became worse with increasing severity
      of liver dysfunction, they changed within the normal limits. Platelet
      aggregability and alpha 2-antiplasmin activity in patients with liver dysfunction
      were remarkably deteriorated beyond normal limits. In conclusion, liver
      dysfunction associated with alcohol consumption appears to be an important factor
      in the deterioration of the clinical status of patients with ICH and may be one
      of the causative factors in the development of ICH. Although mildly impaired
      hemostatic systems may be partially responsible for these adverse effects of
      liver dysfunction on ICH, it seems probable that nonhemostatic mechanisms are
      attributed to the effects.

PMID- 7808602
TI  - A phase II clinical trial of recombinant human tissue-type plasminogen activator
      against cerebral vasospasm after aneurysmal subarachnoid hemorrhage.
AB  - The results of a Phase II clinical trial of intrathecal recombinant tissue-type
      plasminogen activator for the prevention of vasospasm were reported. The subjects
      were 53 patients with aneurysmal subarachnoid hemorrhage (SAH), Groups 2 to 4 in
      Fisher's preoperative computed tomography classification and Grades II to IV in
      the Hunt-Kosnik classification. Twenty-four hours after surgery, tissue-type
      plasminogen activator (TD-2061) was intracisternally administered via a catheter
      (0.1, 0.2, or 0.4 mg, three times daily for 5 days). The clot-dissolving effects
      assessed as "effective" and "markedly effective" were virtually the same in the
      0.1- and 0.2-mg groups (66.7% and 64.3%, respectively) but slightly lower (53.3%)
      in the 0.4-mg group, suggesting an adequate effect in the 0.1- and 0.2-mg groups.
      Severe angiographic vasospasm was not observed in any of three groups. No
      intergroup differences were noted in the incidence of symptomatic vasospasm, low
      density on computed tomography 1 month after SAH, and functional prognosis.
      Bleeding complications were noted in 4 patients (7.5%), including 1 case of SAH
      in the low 0.1-mg group, 2 cases of SAH in the 0.2-mg group, and 1 case of
      epidural hematoma in the 0.4-mg group. In overall safety rating, 3 cases with
      increased SAH and 1 case of epidural hematoma were assessed as "safety doubtful."
      Other minor side effects such as headache and hepatic dysfunction attributed to
      the effect of other simultaneously used drugs were assessed as "almost safe," and
      the rate of "almost safe" and "better" for all dose groups was about 90%,
      suggesting a safe dose level for all groups. These results suggest that repeated
      intrathecal administration of tissue-type plasminogen activator is useful for
      preventing vasospasm even in the low dose of 0.1 mg.

PMID- 7808604
TI  - Nocardial brain abscess: treatment strategies and factors influencing outcome.
AB  - The successful management of nocardial brain abscess remains problematic. The
      authors report 11 cases of nocardial brain abscess treated between 1971 and 1993
      and review 120 cases reported since 1950. The clinical findings included focal
      deficits in 55 patients (42%), nonfocal findings in 36 (27%), and seizures in 39
      (30%). Extraneural nocardiae were present in 66% of the cases; pulmonary (38%)
      and cutaneous/subcutaneous (20%) locations were the most frequent. The abscesses
      were single in 54% of the patients, multiple in 38%, and of unknown number in 8%.
      Forty-four of 131 patients (34%) were immunocompromised; since 1975, 18 of 40
      immunocompromised patients (45%) were transplant recipients and six (15%) had
      human immunodeficiency virus. The mortality rate was 24% after initial craniotomy
      and excision (11/45), 50% after aspiration/drainage (17/34), and 30% after
      nonoperative therapy (7/23); 29 cases (22%) were diagnosed at autopsy. The
      mortality rate was 33% in patients with single abscesses and 66% in those with
      multiple abscesses (P < 0.0003). There was no difference in the mortality rates
      of immunocompromised and nonimmunocompromised patients treated before computed
      tomography (CT) was available; since the advent of CT, however, the mortality
      rate has been significantly higher in immunocompromised patients (55% vs. 20%, P
      < 0.05). Although the mortality rate for nocardial brain abscesses has dropped
      almost 50% since the advent of CT, it has remained virtually unchanged in
      immunocompromised patients and is three times higher than that of other bacterial
      brain abscesses (30% vs. 10%). The authors recommend image-directed stereotactic
      aspiration for diagnosis; however, craniotomy and total excision are necessary in
      most cases, because nocardial abscesses are usually multiloculated. Patients with
      minimal neurological deficits or small abscesses may be treated initially with
      antibiotics alone. Sulfonamides, alone or in combination with trimethoprim, are
      most effective and should be continued for at least 1 year. Minocycline,
      imipenem, or aminoglycoside in combination with a third-generation cephalosporin
      may be used with reasonably good success as second-line agents in cases of
      allergy or nonresponsiveness to sulfa agents.

PMID- 7808603
TI  - Proton magnetic resonance spectroscopy of brain tumors: an in vitro study.
AB  - The ability of proton magnetic resonance spectroscopy (1H MRS) to diagnose brain
      tumors was investigated using in vitro high-resolution spectra. Fifty-eight
      surgically excised samples of brain tumors (12 glioblastomas, 4 anaplastic
      astrocytomas, 6 astrocytomas, 12 meningiomas, 6 neurinomas, 4 chordomas, 3
      craniopharyngiomas, 2 pituitary adenomas, 2 malignant lymphomas, 1 ependymoma, 1
      medulloblastoma, and metastatic brain tumors including 3 pulmonary
      adenocarcinomas, a hepatocellular carcinoma, and a renal cell carcinoma) and 4
      nontumorous lobectomized brains were examined by in vitro 1H MRS. N-Acetyl
      aspartate was demonstrated in normal tissues but could not be detected in
      nonneuroectodermal tumors. Total creatine was decreased in all brain tumors in
      comparison with normal brain tissues, but was relatively higher in
      neuroectodermal tumors than in other brain tumors. Choline-containing compounds
      were present in all tumors except craniopharyngioma, and their concentrations
      were particularly high in a metastatic brain tumor from hepatocellular carcinoma.
      The concentration of glycine was high in neuroectodermal tumors, whereas that of
      taurine was high in medulloblastoma, pituitary adenoma, and renal cell carcinoma.
      Alanine was increased in meningioma, glioma, and pituitary adenoma. Neurinoma had
      the largest inositol content among the tumors examined. Thus each type of brain
      tumor exhibited a characteristic MR spectrum. These data suggested that in vivo
      1H MRS might provide clinically useful information about tumor metabolism and aid
      in the differential diagnosis of tumors. Although excellent anatomical
      localization of tumors can be readily obtained by MR imaging, MRS may provide
      additional information in cases in which the differential diagnosis of tumors by
      MR imaging is difficult.

PMID- 7808605
TI  - Radiological study of symptomatic Rathke's cleft cysts.
AB  - We investigated the relationship between radiological findings and the nature of
      the cyst fluid and histological findings of six Rathke's cleft cysts. The results
      show that the majority (five of six cases) of symptomatic Rathke's cleft cysts
      exhibit no enlargement of the sella turcica on plain x-rays, which may be helpful
      in differentiating cystic pituitary adenoma in the radiological diagnostic
      process. Three cases with large cysts showing high-intensity T1-weighted magnetic
      resonance images harbored abundances of cholesterol crystal and hemosiderin
      pigment in the cyst walls. The high signal intensity in magnetic resonance images
      of Rathke's cleft cysts may be explained by hemorrhage and a deposition of
      cholesterol crystal and may be considered in certain cases of Rathke's cleft
      cyst, especially when they are large.

PMID- 7808606
TI  - Peritumoral edema in meningiomas: microsurgical observations of different brain
      tumor interfaces related to computed tomography.
AB  - Although generally benign tumors, meningiomas may be associated with extensive
      peritumoral brain edema as seen on computed tomographic scans. Fifty-two patients
      with intracranial meningiomas were studied, and the hypodense areas on computed
      tomographic scans were related to the intraoperative microsurgical findings and
      to the sizes of the tumors. We have identified three kinds of tumor-brain
      interfaces characterized by different difficulties in microsurgical dissection:
      smooth type, transitional type, and invasive type. These different microsurgical
      interfaces seem to correlate very precisely with computed tomographic images of
      halo-like and finger-like hypodense areas, allowing prediction of the
      microsurgical effort to be made in the surgery of meningiomas. The size of the
      tumor seems to be important in our subjects in determining the amount of edema
      produced. Indeed, a positive correlation (P < 0.001) was found between the sizes
      of the tumors and the extent of peritumoral hypodensity. A positive correlation
      (P < 0.002) also has been found between grade of edema and cortical penetration.
      Cerebral cortex disruption was systematically observed by us in invasive-type
      meningiomas and in 3 of 21 cases (14.3%) in transitional-type meningiomas. No
      penetration was observed in smooth-type meningiomas.

PMID- 7808607
TI  - Low-pressure hydrocephalic state and viscoelastic alterations in the brain.
AB  - Most shunt-dependent hydrocephalic patients present with predictable symptoms of
      headache and mental status changes when their cerebrospinal fluid shunts
      malfunction. Their intracranial pressure (ICP) is usually high, and they usually
      respond to routine shunt revision. This report describes 12 shunted patients who
      were admitted with the full-blown hydrocephalic syndrome but with low to low
      normal ICP. All 12 patients had been maintained previously on medium-pressure
      shunts. Their symptoms included headache, lethargy, obtundation, and cranial
      neuropathies. At peak symptoms, their ventricular sizes were large
      (ventricular/biparietal ratio of 0.35 to 0.45) in six and massive
      (ventricular/biparietal ratio > 0.45) in six and their ICPs ranged from 2.2 to
      6.6 mm Hg, with a mean of 4.4 +/- 1.3 mm Hg (+/- standard deviation), i.e., below
      or well within the pressure range of their shunts. The pressure volume index of
      three patients at peak symptoms ranged from 39.2 to 48.5 ml, with a mean of 43.9
      +/- 4.6 ml, which represents a 190% increase from the predicted normal value.
      Seven patients failed to improve with multiple shunt revisions, including the use
      of low-pressure valves. In 11 patients, symptoms and ventriculomegaly were not
      reversed except with prolonged external ventricular drainage at subzero pressures
      (mean external ventricular drainage nadir pressure of -5.7 +/- 3.6 mm Hg, for a
      mean period of 22.2 days). During external ventricular drainage treatment,
      symptoms correlated only with ventricular size and not with ICP. All 11 were
      subsequently treated successfully with a new medium- or low-pressure shunt. One
      patient was treated successfully with prolonged shunt pumping. We postulate that:
      1) the development of this low-pressure hydrocephalic state is related to
      alteration of the viscoelastic modulus of the brain, secondary to expulsion of
      extracellular water from the brain parenchyma, and to structural changes in brain
      tissues due to prolonged overstretching; 2) certain patients are susceptible to
      developing low-pressure hydrocephalic state because of an innate low brain
      elasticity due to bioatrophic changes; 3) low-pressure hydrocephalic state
      symptoms are due not to pressure changes but to brain tissue distortion and
      cortical ischemia secondary to severe ventricular distortion and elevated radial
      compressive stresses within the brain; and 4) treatment must be directed toward
      allowing the entry of water into the brain parenchyma and the restoration of
      baseline brain viscoelasticity.

PMID- 7808609
TI  - Repeat operations in failed microvascular decompression for trigeminal neuralgia.
AB  - For the study of pathogenesis and treatment of recurrent trigeminal neuralgia, we
      performed 31 repeat operations from among 400 patients with trigeminal neuralgia
      in the past 10 years. Initially, of these 400 patients, 376 underwent
      microvascular decompression only, and 24 underwent partial sensory rhizotomy with
      or without microvascular decompression. Fifty-three patients (14%) had
      recurrences after microvascular decompression, of which 31 patients underwent
      repeat operations. Among the repeat operations, there was negative exploration in
      16 patients (52%), arterial loop compression in 7 (22%), venous compression in 4
      (13%), and Teflon compression or adhesion in 4 (13%). Twenty-one patients had
      early recurrences within 1 year, and 10 patients had late recurrences. Negative
      exploration and arterial compression were more likely in early recurrence (P =
      0.01). Continuing demyelination might occur in patients with negative
      exploration, even when adequate decompression had been initially performed.
      Seventy percent of the patients had no recurring pain by way of partial sensory
      rhizotomy for negative explorations, redecompression of arterial loops, division
      of offending veins, or lysis and reposition of Teflon. About half of the patients
      had positive findings that were amenable without rhizotomy in the repeat
      operations. A repeat operation for failed microvascular decompression is a good
      choice if the condition of the patient is tolerant.

PMID- 7808608
TI  - Long-term surface cortical cerebral blood flow monitoring in temporal lobe
      epilepsy.
AB  - Long-term subdural surface cortical cerebral blood flow (CBF) and
      electrocorticographic monitoring was performed in 12 patients with complex
      partial seizures. A total of 40 seizures were analyzed. Baseline CBF values from
      nonepileptic and epileptic temporal lobe (mean +/- standard error) were 60.0 +/-
      1.0 and 50.2 +/- 1.8 ml/100 g per minute, respectively (P < 0.05). In general,
      clinical seizure onset was preceded by a 20-minute preictal CBF increase from
      baseline in the epileptic temporal lobe. Peak early postictal CBF values of
      nonepileptic and epileptic temporal lobes were 57.7 +/- 13.3 and 89.0 +/- 21.7
      ml/100 g per minute (P > 0.05) at 5.2 +/- 2.2 and 2.4 +/- 1.0 minutes (P > 0.05)
      after clinical seizure onset, respectively. Statistically significant differences
      between nonepileptic and epileptic temporal lobe CBF were detected at 50 minutes
      (74.0 +/- 14.2 and 37.5 +/- 9.2 ml/100 g per minute, respectively; P < 0.05) and
      60 minutes (75.6 +/- 13.6 and 36.1 +/- 8.5 ml/100 g per minute, respectively; P <
      0.05) postictal. The data suggest that the optimal times for CBF analysis to
      differentiate epileptic from nonepileptic temporal lobe are 1) during the
      interictal period and 2) late (50 to 60 minutes) postictal. The results of this
      study should improve the understanding of the dynamic cerebral perfusion patterns
      in the epileptic human brain.

PMID- 7808610
TI  - Magnetic resonance imaging and microsurgical treatment of intramedullary
      hemangioblastoma of the spinal cord.
AB  - Thirteen cases of intramedullary hemangioblastoma of the spinal cord are
      reported. The tumors were diagnosed with radiological studies, especially
      magnetic resonance imaging. Microsurgery was used to achieve gross total removal
      of the tumors in all cases. Signs and symptoms improved in 84.6% of the patients
      after surgery. The authors describe the diagnosis and microsurgical techniques
      for the excision of intramedullary hemangioblastoma of the spinal cord. This
      disease should be differentiated from hydromyelia, intramedullary ependymoma, and
      vascular malformation of the spinal cord. Total removal of the tumor is
      recommended.

PMID- 7808611
TI  - Functional magnetic resonance imaging of somatosensory stimulation.
AB  - Functional magnetic resonance imaging (FMRI) has detected changes in regional
      cerebral blood flow and volume in response to motor movements, visual stimuli,
      and auditory stimuli in each of their respective primary cortices. This
      experiment was conducted to determine whether signal changes in the somatosensory
      cortex secondary to tactile stimulation could be demonstrated. The palm of the
      right hand was periodically stimulated while the subject was undergoing echo
      planar imaging with a 1.5-T magnetic resonance scanner equipped with local
      gradient and radio frequency coils. Sagittal and coronal images of 10- to 15-mm
      slice thickness were selected to include the postcentral gyrus and surrounding
      regions. Temporally correlated signal changes of 1% to 5% occurred in the peri
      rolandic region in each of six subjects. The time course of signal changes was
      comparable to that found in other primary sensory and motor cortices. The results
      provide preliminary evidence of the sensitivity of FMRI to activation of the
      somatosensory cortex with tactile stimulation and support FMRI as a promising
      noninvasive technique for study of the functional organization and integrity of
      the cerebrum.

PMID- 7808612
TI  - The application accuracy of stereotactic frames.
AB  - The purpose of incorporating stereotactic methodology into neurosurgical
      operations is to achieve a consistently high degree of accuracy in localizing
      intracranial targets. Therefore, the limits of resolution for the operation are a
      function of the accuracy of the particular stereotactic frame system. The total
      clinically relevant error (application accuracy) comprises errors associated with
      each procedural step, including imaging, target selection, vector calculations,
      and the mechanical errors of stereotactic frames. To evaluate these parameters, a
      systematic error analysis was carried out with four commonly used stereotactic
      devices: the Brown-Roberts-Wells, the Cosman-Roberts-Wells, the Kelly-Goerss
      COMPASS (modified Todd-Wells), and the Leksell frames. Over 21,500 independent
      accuracy test measurements were made with 11,000 computed tomograms. The results
      suggest a potentially significant degree of error in the application accuracy of
      all stereotactic instruments, which is accentuated by but not entirely due to
      imaging-associated errors. Clinically encountered levels of weightbearing by
      stereotactic frames may have a pronounced effect on their mechanical accuracy.
      Both the reapplication of aiming arc assemblies and the use of phantom base units
      introduce independent sources of mechanical inaccuracy into stereotactic
      procedures. The scope of individual error values and their determining factors
      must be considered with every clinical use of stereotactic frame systems.

PMID- 7808613
TI  - Characterization of spatial distortion in magnetic resonance imaging and its
      implications for stereotactic surgery.
AB  - The different sources of spatial distortion in magnetic resonance images are
      reviewed from the point of view of stereotactic target localization. The extents
      of the two most complex sources of spatial distortion, gradient field
      nonlinearities and magnetic field inhomogeneities, are discussed both
      qualitatively and quantitatively. Several ways by which the spatial distortion
      resulting from these sources can be minimized are discussed. The clinical
      relevance of the spatial distortion along with some strategies to minimize the
      localization errors in magnetic resonance-guided stereotaxy are presented.

PMID- 7808614
TI  - Hypericin: a potential antiglioma therapy.
AB  - Hypericin, a polycyclic aromatic dione isolated from plants, is presently being
      clinically evaluated as an antiviral agent in the treatment of human
      immunodeficiency virus (HIV) infection. In addition, it is known to be a potent
      protein kinase C inhibitor. To evaluate its potential as an inhibitor of glioma
      growth, an established (U87) and low-passage glioma line (93-492) were treated
      with hypericin in tissue culture for a period of 48 hours after passage.
      Hypericin inhibited the glioma growth in a dose-related manner, with a marked
      inhibition of growth in the low-micromolar concentration range (e.g., in line U87
      and low-passage line 93-492, a concentration of hypericin of 10 mumol/L produced
      62 and 76% decreases in [3H]thymidine uptake, respectively). Because the reported
      inhibitory effects of protein kinase C are enhanced by visible light,
      [3H]thymidine uptake was measured in both the presence and the absence of visible
      light. In glioma line A172, the presence of light slightly increased the
      inhibitory effect of hypericin. Moreover, an apoptosis (i.e., programmed cell
      death) assay was performed to determine whether the treatment of glioma cells
      with hypericin was cytostatic or cytocidal. Cells were harvested, and purified
      deoxyribonucleic acid (DNA) was analyzed by agarose gel electrophoresis. DNA from
      cells treated with hypericin for 48 hours exhibited a classical "ladder" pattern
      of oligonucleosome-sized fragments characteristic of apoptosis. These data
      suggest that the proven safe drug hypericin may have potential as an antiglioma
      agent; we suggest clinical trials.

PMID- 7808615
TI  - Sympathetic mediation of peripheral vasodilation induced by spinal cord
      stimulation: animal studies of the role of cholinergic and adrenergic receptor
      subtypes.
AB  - Electric spinal cord stimulation (SCS) is widely used as a treatment modality for
      ischemic pain in peripheral arterial insufficiency. The background for the
      therapeutic effect may be a temporary inhibition of sympathetically maintained
      peripheral vasoconstriction. In this series of experiments, the involvement of
      different types of cholinergic and adrenergic receptor subclasses in the
      vasodilatory effect was explored in anesthetized rats. The microcirculation in
      hindlimb skin and hamstring muscle was studied by the laser Doppler technique.
      The ganglionic blocker hexamethonium as well as the nicotinic receptor antagonist
      chlorisondamine abolished the effect in both vascular beds, whereas the
      muscarinic receptor antagonists pirenzepine and atropine were ineffective. Among
      the adrenergic receptor active compounds, phentolamine, prazosine (an alpha 1
      receptor antagonist), and clonidine in high doses suppressed the SCS-induced
      vasodilation. Yohimbine (an alpha 2-receptor antagonist) did not alter the
      effect. The beta-adrenergic compounds had a differential effect on muscle and
      skin perfusion. Atenolol, a beta 1-receptor antagonist, inhibited SCS-induced
      vasodilation only in the skin, whereas the beta 2-receptor antagonist butoxamine
      selectively depressed the muscle response. The vasodilatory effect of SCS in the
      animal model used here seems to a large extent to be mediated by an inhibitory
      effect on peripheral vasoconstriction maintained via efferent sympathetic
      activity involving nicotinic transmission in the ganglia and the postganglionic
      alpha 1-adrenoreceptors. The involvement of beta-receptors seems to be different
      in skin and muscle, beta 1 being more important for the changes in the skin and
      beta 2 being more important for those in muscle. The high-intensity antidromic
      response, earlier believed to explain how SCS exerted its vasodilatory effect,
      was resistant to cholinergic and adrenergic manipulations and seems to depend on
      entirely different mechanisms.

PMID- 7808617
TI  - Can academic health centers survive health care reform?

PMID- 7808616
TI  - Light propagation in the brain depends on nerve fiber orientation.
AB  - In this study, the penetration of red laser light (632.8 nm) in fresh bovine
      brain was measured parallel, oblique, and perpendicular to the axis of white
      matter tracts. The measurements were performed in eight samples with an isotropic
      light source and detector and were obtained by advancing the detector tip toward
      the light source in the tissue. A statistically significant difference in the
      effective attenuation coefficient of the light (mueff) was found between the
      parallel and perpendicular directions, 0.47 +/- 0.06 mm -1 and 0.63 +/- 0.13 mm
      1, respectively (P = 0.005). The measurements taken at an angle of 45 degrees in
      the same sample resulted in an intermediate mueff of 0.58 +/- 0.09 mm-1. These
      results suggest a preferential guidance of light along the axis of the white
      matter tracts of the brain.

PMID- 7808618
TI  - Neurolink: a neurosurgical wide-area computer network.
AB  - A computerized system capable of transmitting digitally formatted images of the
      central nervous system has been used to develop a neurosurgical wide-area network
      in western Pennsylvania. This system links remote or primary care hospitals with
      a large, tertiary-care, Level 1 trauma center for the constant availability of
      neurosurgical evaluation by receiving and interpreting computed tomography and
      magnetic resonance images sent via ordinary public telephone lines. This network
      has been used in over 20 cases to receive and interpret transmitted cranial
      computed tomographic images consisting of subarachnoid hemorrhage, intracerebral
      hematoma, cerebral neoplasm, cerebral abscess, cerebrovascular accident, and
      normal studies. There has been no known instance of false-positive or false
      negative interpretation or of a patient being adversely managed by this method.
      On the contrary, it appears that patient management has been positively affected
      through the ability of the neurosurgical evaluation to include a review of the
      radiological studies. The initial experience has led to the conclusion that this
      network is an effective, accurate, and cost-effective means of delivering
      neurosurgical care to underserved areas.

PMID- 7808619
TI  - New observations on the Dandy-Cushing controversy.
AB  - It is generally known that the relationship between the two preeminent American
      neurosurgeons, Harvey Cushing and Walter Dandy, was strained and far from
      amicable. Their differences began when both men were at Johns Hopkins and
      continued when Cushing moved to Boston and Dandy remained in Baltimore.

PMID- 7808620
TI  - Neurocutaneous melanosis presenting as an intradural mass of the cervical canal:
      magnetic resonance features and the presence of melanin as a clue to diagnosis:
      case report.
AB  - We present a case of neurocutaneous melanosis in a 1-year-old child who presented
      with progressive quadriparesis created by an infiltrating extra-axial neoplastic
      melanin-producing tumor at the foramen magnum. This extensive intra-arachnoid
      mass filled the basal cisterns of the brain and surrounded the upper cervical
      cord. An imaging clue to the diagnosis was apparent as T1-weighted shortening on
      magnetic resonance in the pia and/or cortex of the cerebellar folia, suggesting
      the presence of melanin.

PMID- 7808621
TI  - Multiple plasma cell granulomas of the central nervous system: case report.
AB  - Plasma cell granulomas of the central nervous system are exceedingly rare. Of the
      six well-documented cases that have been published to date, five plasma cell
      granulomas were intracranial and one was located in the spinal meninges. Multiple
      plasma cell granulomas of the central nervous system have not previously been
      reported. We now report a patient who had two plasma cell granulomas in the
      spinal meninges and one in the anterior cerebral falx. The histological findings
      that differentiate this rare lesion from other central nervous system lesions,
      such as plasmacytoma and meningioma, are discussed with a review of the
      literature.

PMID- 7808622
TI  - A neonatal huge subependymal giant cell astrocytoma: case report.
AB  - We report a neonate with a huge subependymal giant cell astrocytoma associated
      with tuberous sclerosis, with atypical magnetic resonance imaging findings. The
      neonatal subependymal giant cell astrocytoma is rare, and we discuss the
      difficulty in its diagnosis and treatment.

PMID- 7808623
TI  - Endoscopic resection of a subthalamic cavernous angioma: technical case report.
AB  - Endoscopic resection of a cavernous angioma at the subthalamic region was
      performed in a 33-year-old woman who presented with diplopia and progressive
      hemiparesis caused by recurrent hemorrhages. The entire surgical procedure was
      done through an 8-mm guiding tube inserted stereotactically from a frontal burr
      hole via an approach that traversed the anterior limb of the internal capsule.
      The patient's symptoms improved after surgery. This is believed to be the first
      report describing successful resection of a cavernous angioma located at the
      subthalamic region.

PMID- 7808624
TI  - Direct thrombosis of a pseudoaneurysm after obliteration of a carotid-cavernous
      fistula with cellulose acetate polymer: technical case report.
AB  - A 55-year-old man who suffered a head injury resulting in a left traumatic
      carotid-cavernous fistula was successfully treated with an intravascular
      detachable balloon. A pseudoaneurysm formed adjacent to the balloon. Seven months
      after the initial procedure, treatment with cellulose acetate polymer, a new
      liquid thrombotic material, occluded the pseudoaneurysm and preserved the
      internal carotid artery.

PMID- 7808625
TI  - Electrophrenic respiration after intercostal to phrenic nerve anastomosis in a
      patient with anterior spinal artery syndrome: technical case report.
AB  - Long-term positive pressure mechanical ventilation has been the standard of care
      for patients with respiratory insufficiency caused by high cervical spine injury.
      Stimulation of the phrenic nerves, and thus the diaphragm, with an implanted
      phrenic nerve pacemaker has provided adequate ventilation and an alternative to
      the standard. Diaphragmatic pacing, also known as electrophrenic respiration,
      requires an intact phrenic nerve to act as a conduit for the applied stimulus.
      Propagation of the stimulus is impossible if the injury sustained has led to
      axonal loss in the phrenic nerve. This may be expected if the damage to the
      spinal cord is at the C3-C5 level. If the cell bodies of the motor neurons in
      this region have been damaged, or direct injury to the phrenic nerve has
      occurred, then diaphragmatic pacing is not feasible by the traditional method.
      Microsurgical repair of peripheral nerves and nerve grafting have provided the
      impetus for research into anastomosis of a viable intercostal nerve to a
      nonfunctional phrenic nerve, with subsequent reinnervation of the diaphragm. Once
      successful axonal regeneration and diaphragmatic reinnervation have occurred, the
      distal phrenic nerve may then be paced. This case documents the first successful
      institution of electrophrenic respiration after intercostal to phrenic nerve
      anastomosis.

PMID- 7808626
TI  - Stereotactic gamma-thalamotomy with a computerized brain atlas: technical case
      report.
AB  - Radiosurgical stereotactic thalamotomy was performed in a patient with
      parkinsonian tremor with a computerized stereotactic brain atlas, which was
      transformed to fit the patient's thin-sliced magnetic resonance image to select
      an optimal target in the nucleus ventralis intermedius of the thalamus. The
      patient's tremor and rigidity disappeared and have not appeared again for more
      than 1 year since the eighth postoperative month. A method for converting the
      presurgically planned stereotactic coordinates in the atlas coordinate system to
      the coordinates in the frame coordinate system is described.

PMID- 7808627
TI  - A wrapping clip combined with silastic sheet for emergent hemostasis: technical
      note.
AB  - The attachment of a thin silastic sheet combined with the use of Sugita's
      fenestrated aneurysm clip was developed for the emergency repair of vascular
      perforation during surgery. The sheet is flexible and tailored in the operating
      room, corresponds to the vascular curve, and is semitransparent, allowing
      observation of the area of perforation. The device can be applied under severe
      bleeding conditions without temporary clipping. It may be useful as an emergency
      tool for vascular repair in the operating room.

PMID- 7808628
TI  - Intratumoral embolization of intracranial and extracranial tumors: technical
      note.
AB  - A new technique of intratumoral embolization is described. An intratumoral
      injection of N-butylcyanoacrylate is performed either perioperatively by direct
      puncture of the tumor or preoperatively through the nose or through the skin. The
      indications for this technique are hypervascularized tumors, such as juvenile
      angiofibroma, hemangiopericytoma, or paraganglioma. This technique has been
      applied in 21 patients with excellent results in terms of devascularization.

PMID- 7808629
TI  - Intraoperative monitoring of the vagus nerve during intracranial glossopharyngeal
      and upper vagal rhizotomy: technical note.
AB  - Intracranial section of the glossopharyngeal and upper vagal rootlets for the
      treatment of vagoglossopharyngeal neuralgia may cause dysphagia or vocal cord
      paralysis from injury to the motor vagal rootlets in 10% to 20% of cases. To
      minimize this complication, we recently applied a technique of intraoperative
      monitoring of the vagus nerve (previously described by Lipton and McCaffery to
      monitor the recurrent laryngeal nerve during thyroid surgery) in a patient
      undergoing intracranial rhizotomy for vagoglossopharyngeal neuralgia. By
      inserting an electrode in the ipsilateral false vocal cord and stimulating the
      rostral vagal rootlets intraoperatively under general anesthesia, we could
      differentiate the rostral vagal motor rootlets from the sensory rootlets. In this
      patient, the technique allowed us to preserve a rostral vagal rootlet, which if
      sectioned, could have caused dysphagia or vocal cord paralysis. We conclude that
      intraoperative monitoring of the rostral vagal rootlets is an important technique
      to minimize complications of upper vagal rhizotomy.

PMID- 7808630
TI  - Interdisciplinary evaluation of cerebral hemodynamics in the treatment of
      arteriovenous fistulae associated with giant varices.
AB  - The techniques for the treatment of intracranial arteriovenous fistulae include
      angiographic balloon occlusion of the fistula as well as direct surgical attack.
      Regardless of the method, the occurrence of severe hyperemia caused by a lack of
      autoregulation after obliteration of the fistula remains a significant concern.
      We report the use of single photon emission computed tomography and transcranial
      Doppler studies to assess the occurrence of hyperemia during trial balloon
      occlusion of such fistulae in two patients. Single photon emission computed
      tomography and transcranial Doppler studies confirmed the lack of hyperemia
      during the test occlusion, allowing consideration of treatment plans involving
      acute fistula occlusion without the difficulty imposed by gradual occlusion and
      permitting a more accurate evaluation of risk. The purpose of this report is to
      illustrate how clinical evaluation of intracranial hemodynamics can contribute
      significantly to treatment decisions.

PMID- 7808631
TI  - Electroconvergent cautery.
AB  - A new cautery system known as the electroconvergent cautery system is described.
      This cautery system uses a radiofrequency current of 13.56 MHz. The current is
      passed through an amplifier, an impedance matching system, and a loading and
      tuning coil into a probe. After the probe tip is touched to the tissue, the
      mismatch of impedance between the probe tip and the generator is minimized to
      almost zero, resulting in high-current density at the probe tip, which causes
      pinpoint heating of the tissue at the point where it is touched by the probe
      without spread of heat to the surrounding tissue. This heat can cut and vaporize
      tissue and coagulate vessels. The probe can also be used to coagulate vessels
      with standard surgical forceps. Because convergence of energy is used for tissue
      heating, a grounding pad is not needed. The system can also be used under
      cerebrospinal fluid or saline.

PMID- 7808632
TI  - Historical perspective. David Ferrier (1843-1928).

PMID- 7808633
TI  - Somanetics INVOS 3100 cerebral oximeter.

PMID- 7808634
TI  - Osteoma of the frontoethmoidal sinus with secondary brain abscess and
      intracranial mucocele: case report.

PMID- 7808635
TI  - Cost and survival analysis of metastatic cerebral tumors treated by resection and
      radiation.

PMID- 7808636
TI  - Formation of hypothalamic regulation of the gonadotropic function of the
      hypophysis under the conditions of hypoinsulinemia in rats.

PMID- 7808637
TI  - Integrative activity of the neuron: the specific characteristics and plasticity
      of systemic mechanisms.
AB  - The notions of P. K. Anokhin regarding the integrative activity of neurons
      through the time course of the systemic organization of behavioral acts are
      developed in this article. It is shown that in the systemic organization of
      behavioral acts neurons in their activity not only initial motivations and
      reinforcement, but demonstrate anticipatory reactions on the basis of preceding
      reinforcements, including themselves in the formation of the apparatus of the
      acceptor of the result of an action. A dominant motivation substantially alters
      the sensitivity of brain neurons to neuromediators and neuropeptides. Change in
      the chemical sensitivity of neurons has been identified through the time course
      of the organization of the various stages of systemic organization of behavioral
      acts. It has been established that the sensitivity of neurons to motivational and
      sensory influences, as well as to biologically active substances is also
      determined to a substantial degree by their protein-synthesizing apparatus.
      Investigations have demonstrated the specific characteristics and plasticity of
      neurons in the systemic organization of behavioral acts.

PMID- 7808638
TI  - Neurochemical cellular mechanisms of the assessment of the results of behavioral
      activity.
AB  - Neurons of the visual area of the cerebral cortex of cats were investigated at
      various stages of alimentary instrumental behavioral activity. The impulse
      activity of the neurons was recorded both during standard food-procuring behavior
      and during the performance of an instrumental reaction without reinforcement.
      Biologically active substances were applied microiontophoretically to the neurons
      in the experiment. Varying chemical sensitivity of individual neurons to
      neuromediators was established in both experimental situations, as was the
      significance of the mechanisms of protein synthesis for these processes.

PMID- 7808639
TI  - Reflection of the systemic mechanisms of instrumental behavior in the activity of
      brain neurons.
AB  - Changes in the impulse activity of neurons of the sensorimotor, parietal
      associative, and visual areas of the cerebral cortex were studied during the
      performance of conditioned instrumental alimentary behavior by an animal.
      Comparative analysis of impulse activity of the neurons investigated showed that
      71.4% of the cells of the parietal associative area of the cerebral cortex were
      activated when the conditional stimulus was turned on; 75.8% of neurons of the
      visual cortex were activated when the animal pressed the pedal; 82.5% of the
      cells of the somatosensory and 75.8% of the visual area of the cerebral cortex
      increased activity upon appearance of milk in the food dispenser. During lapping
      of the milk, 75.8% of cells of the visual cortex showed reduction of activity.
      Reorganization of the impulse activity of individual neurons of the cerebral
      cortex reflected the unfolding of pretriggering integration formed as the result
      of preliminary training of the animal. The character of the impulse activity of
      the neurons investigated at the stage of realization of the program of the action
      and obtaining of reinforcement was determined primarily by the streams of
      afferent excitations arising during the perception of parameters of the stage
      related and final results of the behavior.

PMID- 7808640
TI  - Molecular-cellular mechanisms of learning of the common snail.
AB  - The development of sensitization and an associative habit of rejection of a
      specific type of food is accompanied by short-term and long-term changes in
      behavior, bioelectrical activity, and the dynamics of the content of Ca(b) in the
      command neurons of defense behavior of the common snail. In approximately an hour
      from the moment of the beginning of training, behavioral and neurophysiological
      effects which were similar on the whole were identified during the development of
      these habits. During the development of sensitization, the responses to test
      tactile stimulations and to applications of quinine and carrot juice appeared
      and/or were markedly intensified from 50 through 90 min from the moment of the
      first sensitizing stimulation. During the development of conditioning, responses
      to the tactile stimulations and quinine also appeared and/or intensified from 50
      60 min, while responses to the conditional stimulus appeared and intensified
      approximately 30 min later (from 85-95 min). Phases of an initial marked
      increase, with a subsequent tendency to stabilization, in the level of Ca(b) were
      observed in the command neurons during a brief period in the development of
      sensitization; during conditioning a temporary decrease was identified in the
      content of Ca(b) in response to each combination of stimuli with its subsequent
      spontaneous decrease at 40-60 min. An increase in the level of Ca(b), beginning
      during the development of sensitization from 50-60 min, and during conditioning
      from 85-90 min from the moment of the beginning of training, was observed in the
      long-term period.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7808641
TI  - Influence of an antioxidant on the impulse activity of neurons of the prefrontal
      and inferotemporal cortex during visual recognition in monkeys.
AB  - The impulse activity of individual neurons of the prefrontal and inferotemporal
      cortex was recorded during the performance of a task of delayed visual
      differentiation of stimuli of various colors in monkeys before and after the
      systemic administration of the antioxidant, oxymethacil (4-5 mg/kg). The
      improvement in cognitive characteristics induced by oxymethacil was accompanied
      by changes in the activity of neurons of the prefrontal cortex in which
      activation dependant upon the stage of recognition and intensifying during an
      increase in the duration of the delay predominated. Inhibition of activity
      predominated during recognition without delay in these neurons; by contrast,
      activation predominated in neurons of the inferotemporal cortex under these
      conditions. During delayed differentiation, the activity of these neurons under
      the influence of oxymethacil changed principally in the same way as in neurons of
      the prefrontal cortex: activation predominated in the majority of the stages of
      recognition. Oxymethacil induced a substantial increase in the coefficients of
      cross correlation between simultaneous respondent reactions of groups of neurons
      in these different areas of the cortex. The results obtained attest to the
      contribution of neuronal structures of the prefrontal and inferotemporal cortex
      to the improvement of cognitive characteristics of monkeys in the presence of the
      effect of oxymethacil, and to the increase in synchronization of informational
      processes in these regions of the cortex.

PMID- 7808642
TI  - Participation of cholinergic structures of the prefrontal and inferotemporal
      cortex in the processes of visual recognition in monkeys.
AB  - Monkeys performed a task of delayed visual differentiation of differently colored
      stimuli in behavioral experiments. The impulse activity of individual neurons of
      the prefrontal and inferotemporal cortex before and after the systemic
      administration of a blocker of M-cholinoreceptors, amyzil (0.8-1.0 mg/kg), was
      recorded simultaneously. Deterioration of the characteristics of recognition
      induced by amyzil was accompanied mainly by a significant increase in the
      activity of neurons of the prefrontal cortex which was dependant on the stage of
      recognition, and intensified with an increase in the delay interval. The impulse
      activity of the neurons of the inferotemporal cortex varied in the process
      without a regular pattern: at some stages of recognition it increased, at others
      it was inhibited. Amyzil induced a substantial decrease in the coefficients of
      cross correlation between the simultaneous respondent reactions of groups of
      neurons of the prefrontal and inferotemporal cortex. The results obtained point
      to the fact that the cholinergic structures of the inferotemporal and prefrontal
      cortex participate, at various stages of visual recognition in monkeys, in the
      formation of the dynamic functional systems which make their specific
      contribution to informational processes.

PMID- 7808643
TI  - Influence of glutamate on the content and metabolism of dopamine in the
      nigrostriatal system of rats distinguished by capacity for learning.
AB  - The effect of repeated (over the course of nine days) intrastriatal
      microinjections of glutamate (5 or 0.5 micrograms in 0.75 microliters of
      physiological solution daily) were investigated in 42 male Sprague-Dawley rats.
      Twenty-nine rats were preliminarily trained in a Skinner box using food
      reinforcement. It was demonstrated that the administration of glutamate to rats
      not subjected to training increases the content of homovanillic acid in the
      striatum. A similar influence in rats that are capable of learning leads to an
      increase in the content of dopamine and a decrease in the level of homovanillic
      acid in this nucleus, while it does not induce changes in the biochemical
      indicators under investigation in those rats that are incapable of learning.
      Microinjections of glutamate also do not alter the capacity for learning in any
      of the groups of animals. The possible causes for the different influence of
      intrastriatal microinjections of glutamate on the activity of the nigrostriatal
      system of rats differing by capacity for learning are discussed.

PMID- 7808644
TI  - Ontogenesis of the establishment of various forms of higher nervous activity.

PMID- 7808645
TI  - [Reduced glutathione and L-cysteine in endotoxic shock in the rat].
AB  - BACKGROUND: Reduced Glutathione (GSH) is a well known physiological antioxidant,
      that would protect against lethal effects of endotoxin. However, the site of the
      action of GSH can be intracellular (transmembrane passage of constitutive amino
      acids) or extracellular (membrane thiols). AIM OF THE WORK: To search if L
      cysteine (one of three constitutive amino acids of GSH) protects against
      endotoxin as GSH and to search if inhibition of transmembrane passage of GSH and
      L-cysteine by Probenecid affects that protection. MATERIALS AND METHODS: Rats
      injected (n = 99) with a lethal dose of endotoxin (BACTO, DIFCO lab. 0111:B4 10
      mg/kg ip) immediately after received: (a) Saline solution; (b) GSH 500 mg/kg; (c)
      L-Cysteine 0.25 g/kg; (d) Probenecid 25 mg/kg in 20% Ethanol plus GSH 500 mg/kg;
      (e) Probenecid 25 mg/kg in 20% Ethanol; (f) 20% Ethanol. The administration of
      Saline solution, GSH, L-cysteine was repeated two hours later. Injection volume
      was 0.5 ml ip. Survival rate of each group of rats was evaluated 6, 12 and 24
      hours after endotoxin injection. Survival was compared with that of the control
      group by Fisher test. RESULTS: GSH and L-cysteine significantly increase survival
      if compared to all other treatments (respectively p < 0.002 and p < 0.001 at 12
      hours; p < 0.005 and p < 0.0002 at 24 hours). Probenecid nullifies the survival
      increase caused by GSH. Probenecid alone or Ethanol alone show a survival rate
      not significantly different in respect to control group. CONCLUSIONS: Protection
      exerted by GSH against fatal effects of endotoxin is also provided by one of its
      constituent amino acids (L-cysteine) and is inhibited by Probenecid. So we can
      infer that such an antioxidant action happens at an intracellular site. Need of
      high doses of GSH and L-cysteine can be due to the necessity of a strong
      concentration gradient between extra and intracellular sites.

PMID- 7808646
TI  - Leukotrienes and alpha tumor necrosis factor levels in the bronchoalveolar lavage
      fluid of patient at risk for the adult respiratory distress syndrome.
AB  - OBJECTIVE: To examine bronchoalveolar lavage (BAL) fluid of patients at risk for
      Adult Respiratory Distress Syndrome in the attempt to provide evidence of an
      increased local production of Leukotrienes (LTS) and Tumor Necrosis Factor (TNF).
      DESIGN: Prospective, comparative, clinical study. SETTING: ICU in a university
      hospital. PATIENTS: 14 patients at risk for ARDS and 10 control patients
      undergoing mechanical ventilation, were studied. INTERVENTION: BAL was performed
      in each patient at the time admission to the ICU (T0), and after 48 hours (T1).
      RESULTS: Our controls never showed levels of TNF > 10 pg/ml and their LTS amounts
      were always below the detection limit. All patients at risk had levels of TNF
      ranging between 22 and 130 pg/ml, but no difference was noticed between patients
      who developed ARDS and those who did not, between survivors and non survivors,
      and between septic and non septic patients. LTD4 and LTB4 (ranging between 30 to
      1365 pg/ml) were detected only in six of the 14 patients. Among these 6 patients,
      4 developed ARDS. In these patients we could correlate LTB4 with TNF levels and
      the number of neutrophils recovered from the BAL fluid. CONCLUSION: In our
      patients leukotrienes and TNF in the BAL fluid correlate well with the acute
      inflammatory phase of ARDS, as reflected by the increase number of leukocytes in
      the fluid retrieved, but they do not appear to be clearly predictive index for
      the syndrome.

PMID- 7808647
TI  - [Changes in immune status due to anesthesia and surgical intervention. The role
      of thymopentin and interleukins].
AB  - OBJECTIVE: Purpose of the study was clinical evaluation of thymopentin and
      interleukins in the changes of immunity due to anesthesia and surgical operation.
      DESIGN: After randomization the patients were divided into four groups according
      to starter type (thiopental or propofol) and immunological pre-treatment
      (tymopentin or saline of control group) administered for three days before and
      two days after operation. SETTING AND PATIENTS: The study was effected on 40
      patients undergoing venous vascular surgery in operating rooms of Medical School
      of University of Genoa. MEASUREMENT: At pre-established times (basal, before and
      after induction, recovery and 72 postoperative hours) were measured some
      immunological data (plasmatic concentrations of red blood cells, white blood
      cells, lymphocyte cells, antibodies, complement analysis, interleukins 1 and 2).
      RESULTS: The results show a depression of immunity with hypoleucocistosis and
      hyperlymphocytosis due to surgical trauma or to anesthesia drugs. CONCLUSIONS:
      Pre-treatment with thymopentin no change perioperative immunity and the role of
      interleukins isn't clear; the immunological depression is the same in thiopental
      of propofol groups.

PMID- 7808648
TI  - [Blood glucose and intracranial surgery].
AB  - When there is a cerebral ischemia, the use of glucose seems to be
      contraindicated. Seventeen non diabetic patients, scheduled for elective
      intracranial surgery (mean surgical time: 218.8 +/- 42.8 min), exhibited no
      hypoglycaemic episodes during surgery without dextrose. The authors conclude that
      dextrose can be avoided without sequelae during intracranial surgery.

PMID- 7808649
TI  - [Double-blind placebo-controlled study of the effectiveness and tolerability of
      10 and 30 mg ketorolac tromethamine suppositories in post-cholecystectomy pain].
AB  - OBJECTIVE: To evaluate the efficacy and tolerability of ketorolac tromethamine 10
      mg and 30 mg suppositories in comparison to placebo, after single dose
      administration in patients suffering from post-operative pain after
      cholecystectomy. DESIGN: Double-blind, randomized, controlled study. SETTING:
      Anaesthesia Service. PATIENTS: 99 patients with severe pain following surgery.
      INTERVENTIONS: Cholecystectomy. MEASUREMENTS AND MAIN RESULTS: The analgesia
      activity of ketorolac tromethamine 10 mg and 30 mg suppositories were evaluated
      after single dose administration by assessing pain intensity and pain relief
      using a 4 point scale (VRS). At the end of the treatment period overall
      assessment of safety and efficacy were recorded by physician and patient. The
      results show that in both active groups after 30' and until 4 hours, pain
      intensity decreased significantly with respect to the baseline. However a
      statistically significant difference between groups of p < 0.02, p < 0.01 and p <
      0.05 was found in favour of the 30 mg dose respectively at 30', 6 and 8 hours
      after administration. All the patients treated with placebo suppositories
      required another rescue analgesic drug and withdrew from the trial. Three
      patients complained adverse events not related to treatment: two on placebo and
      one on ketorolac 10 mg. The systemic and local tolerability of the drug was good.
      CONCLUSIONS: This study shows that ketorolac 30 mg suppositories are effective in
      clinical conditions, such as after surgery, in which pain control must be
      achieved within the shortest time interval and maintained or improved by means of
      a single route of administration.

PMID- 7808650
TI  - [Low-flow anesthesia: isoflurane increment kinetics as a function of the rotatory
      circuit volume].
AB  - OBJECTIVE: Study of the increment of isoflurane volume concentration in two
      rotatory circuits having different capacity during low flow narcosis. DESIGN:
      Descriptive comparison of different halogenate concentration in circuits
      connected to two patient groups and evaluation of the significance of the
      observed differences. SETTING: Surgery theatres of a district Public Hospital.
      PATIENTS: 16 female patients included in the same age, weight and body surface
      group, showing neither obstructive nor restrictive lung diseases. According to
      the surgical treatment used (abdominal or major gynecological surgery) the
      patients were then divided into two groups of 8 each. MEASUREMENTS AND MAIN
      RESULTS: After opening the halogenate nebulizer, dry measurement of the
      isoflurane concentration detected for 30 minutes in the inspiratory and
      expiratory circuit segment by means of monitors at pre-determined intervals,
      before abdominal or major gynecological surgery. Simultaneous measurement of
      isoflurane uptake by means of indirect methods (heart frequency, average arterial
      pressure, use of muscle relaxing agents). The analysis of the measured values
      showed higher isoflurane concentrations and a faster percent increase in the
      small circuit than in the big one (resp. 0.9% vs 0.71% in the inspiratory segment
      and 0.59% vs 0.4% in the expiratory one, with p < 0.005 and I.C. = 99.00%).
      CONCLUSIONS: This study demonstrates how the different kinetics of the isoflurane
      increment in the rotatory circuit is mainly related to the circuit volume. To
      eliminate the problems due to the "low compliance" of the small circuit
      (collection of toxic gases) and to the "high compliance" of the big circuit
      rotatory (awareness), circuits with varying volume might be introduced.

PMID- 7808651
TI  - [Use of pulse oximetry in the diagnosis of accidental bronchial intubation during
      laparoscopic surgery. Description of a clinical case].
AB  - In the present article a case of accidental bronchial intubation during
      laparoscopic cholecystectomy is described. Endotracheal tube was probably
      displaced by gas distension of the abdomen during laparoscopy. Indeed, under
      these circumstances, carina may move cephalad. Initially, tube displacement was
      not diagnosed by either auscultation of breath sounds, or ETCO2 monitoring.
      Instead, a decrease in arterial oxygen saturation, as monitored by pulse
      oximetry, quickly allowed diagnosis and correction of the problem. It is
      concluded that pulse oximetry is more sensitive than other methods in providing
      early warning of tube displacement during laparoscopy.

PMID- 7808652
TI  - [Energy expenditure during a pregnancy complicated by post-traumatic coma:
      analysis of 2 clinical cases].
AB  - OBJECTIVE: To analyze the measured resting energy expenditure, the clinical
      evolution and the nutritional therapy of two pregnant women complicated by post
      traumatic coma and sepsis. DESIGN: Clinical study. SETTING: The ICU of
      Neurosurgery in Regional Hospital in Italy. PATIENTS: Two subjects with head
      trauma due to a motor vehicle accident. METHOD: The resting energy expenditure
      was measured (M-REE) by indirect calorimetry by oxygen consumption (VO2) and
      carbon dioxide production (VCO2). Values were controlled in patients with a
      hemodynamic stability every 4 hours. Predicted REE (P-REE) was calculated
      according to the Harris-Benedict formula. A total parenteral nutrition (1.2-1.3 x
      M-REE) composed of dextrose (70-80% of total caloric amount) and fat (20-30%) was
      infused in both the subjects. As an average 12-15 g of nitrogen were infused
      daily. RESULTS: VO2 and VCO2 increased during the study (case 1: from 225 +/- 33
      to 325 +/- 35 ml/min; p < 0.02; LR: p < 0.0001; VCO2: from 170 +/- 24 to 289 +/-
      23 ml/min; p < 0.0001. Case 2: VO2: from 239 +/- 22 to 315 +/- 35 ml/min; p <
      0.05; LR: p < 0.01. VCO2 from 177 +/- 31 to 247 +/- 22 ml/min; p < 0.05; LR: p <
      0.001). M-REE/kg increased with statistical significance during the study (case
      1: from 23.6 +/- 4.1 to 34.1 +/- 4.3, p < 0.05, LR: p < 0.005; case 2: from 23.7
      +/- 5.8 to 33.4 +/- 7.7, p < 0.05, LR: p < 0.05). A physiological variation in
      oxidative capacity on nutritional substrates was reported throughout the study.
      CONCLUSION: Sepsis and miscarriages following trauma seem to be the cause in an
      increase of the energy expenditure rather than pregnancy itself. However our
      observations must be viewed with caution because they are based on a small number
      of patients.

PMID- 7808653
TI  - [Complete neurological recovery following prolonged cardiac arrest. Description
      of a clinical case].
AB  - We report a case of protracted intraoperative cardiac arrest (15 minutes),
      occurring in a patient with haemorrhagic shock in consequence of a bullet wound
      to the right hemithorax; external cardiac massage was immediately started and
      carried on until the restoration of spontaneous cardiac activity. In the
      immediate postoperative period, the patient presented seizure activity, treated
      with TPS in continuous infusion (2 mg/kg/h) and DPH (250 mg/die). Anticonvulsant
      therapy didn't allow a correct neurologic evaluation of the patient; that was
      possible only when treatment was suspended (4 days after ICU admission).
      Neurophysiological investigations (EEG and Somato-Sensorial Evoked Potentials)
      were undertaken; particularly SSEPs recorded no pathologic alteration of the
      cortical response. At the discharge from ICU the patient was completely awake
      after coma, a residual paresis of the right lower limb was present. We suggest
      that in post-anoxic coma, when anticonvulsant therapy is required,
      neurophysiological investigations improve the accuracy of early outcome
      prediction.

PMID- 7808654
TI  - [Adenocarcinoma of the jejunum. Case report].
AB  - The authors report a case of adenocarcinoma of jejunum and remark the rarity of
      this pathology. Because of poor specificity of the symptoms very seldom a early
      diagnosis is very seldom made and that explains the rare opportunity of radical
      surgical therapy and the frequently bad prognosis of this neoplasm.

PMID- 7808655
TI  - [Perforated diverticulum of the cecum: conservative therapy or resection?].
AB  - The diverticulum of the right colon is a rare disease in Western Countries but is
      very common in Eastern races. The etiology is usually congenital in the lesions
      limited to the cecum (true diverticulum). The diagnosis is rarely made
      preoperatively. The most useful help is from CT and US. Because the clinical
      features suggest an acute appendicitis, in most cases of appendicectomized
      patients the intervention is made without any other investigations. At
      laparotomy, when the diverticulum is surely identified, a conservative treatment
      is recommended (diverticulectomy or invagination). If there are some doubts an
      ileo-colic resection is more opportune. After recovery it is useful to study the
      colon with an Rx clisma.

PMID- 7808656
TI  - [Pulmonary lymphangioleiomyomatosis. Case report].
AB  - Pulmonary lymphangioleyomiomatosis (LAM) is a rare disease that affects only
      women. About one hundred cases are reported in the literature. This disease
      progresses to respiratory failure and its course can be slowed by hormonal
      therapy. A new case is reported; this woman was admitted to our Division for a
      right hydropneumothorax and after pleural drainage fluid demonstrated to be a
      chylous effusion; after a thoraco-abdominal CT scan the diagnosis of LAM was
      suspected. She was operated on after a few days because of continuous air and
      chyle leakage. A closure of lung leakage was performed with a stapler device that
      allowed the removal of a small specimen of lung for histopathological examination
      and a parietal pleurectomy was added with the aim of obtaining a pleural space
      obliteration. The histopathological examination revealed changes consistent with
      LAM and also positive was the hormonal steroid receptors assay. Adhesion of the
      lung to the chest wall was obtained but an antero-basal pouch persisted with
      continuous chylous leakage. A transposition of omentum into the chest was made
      with the aim of obliterating the pouch and favour chyle reabsorption and no
      drainage was left. Another CT scan demonstrated complete obliteration of the
      pouch and no fluid accumulation; the procedure proved to be successful and the
      patient was discharged with hormonal therapy.

PMID- 7808657
TI  - [Description of two cases of retrobrachiocephalic thymus gland].
AB  - We report two rare cases of thymus gland found behind the left brachiocephalic
      vein, in young women undergoing thymectomy for myasthenia gravis. Our
      observations are included among the thymic anatomical variants. After a review of
      the literature on the subject, we discuss both the diagnostic role of new
      radiological techniques (CT, NRM) and the choice of surgical approach to these
      variants.

PMID- 7808658
TI  - [Axillo-femoral bypass in the treatment of aorta prosthesis infection. A special
      case].
AB  - The authors report a case recently brought to their observation: T.A., a 77 year
      old patient, operated on in July 1990, for aortic aneurysm with axillo femoral by
      pass. The patient was reoperated on the 5th day for ischaemic necrosis of the
      descending colon. In 1992 he was operated in another hospital for right iliac
      branch removal of the by-pass and performing of extra-anatomic bifemoral by-pass
      for right iliac branch infection of anatomic prosthesis. He was brought to our
      observation in March 1993, after the patient was refused in other Centres because
      of purulent abscess located near the aortic prosthesis and in the right iliac
      fossa, with a fistula to right superior anterior iliac crista. The patient was
      operated on in April 1993, with an explorative laparatomy to drain the abscess
      and to remove the aortic prosthesis. The aorta was sutured with closed bottom by
      means of delayed points. The postoperative course was regular and an
      arteriography performed three months after confirms the good running of the
      axillo-femoral by-pass and of the bifemoral one previously performed. The authors
      because of their experience and the bibliographical data underline the goodness
      of the axillo-femoral by-pass in serious infections of an aortic prosthesis.

PMID- 7808659
TI  - [Liposarcoma in the submandibular region. Clinical case].
AB  - The authors report a case of liposarcoma in the sub-mandibular region, and they
      describe the histological species and the way of spreading. They suggest a
      surgical, non-demolitional therapy, that they carried radical if it is related to
      a strict follow-up. Anatomical and functional results, after demolishing surgical
      therapy, are sometimes unacceptable if the real benefits in terms of survival are
      considered. No supporting therapy has been used because of the presumed
      insensibility of the neoplasm to the chemo-radiotherapeutic treatments. At 2
      years from surgical treatment no local relapses, on distance metastasis have been
      related.

PMID- 7808660
TI  - [Ultra-short and short surgical prophylaxis with pefloxacin].
AB  - A multicentre study has been done to evaluate the effectiveness and safety of
      pefloxacin, a new fluoroquinolone, when given intravenously for surgical
      prophylaxis. 440 patients (224 males, 216 females), mean age 51.7 +/- 27.3 (SD)
      years and mean weight 68.4 +/- 12.6 kg, were admitted to the study. The diagnoses
      for admission included several surgically treated specialties (obstetrics and
      gynecology, orthopedics and traumatology, oncology and general surgery).
      Pefloxacin was provided in 5 ml ampoules containing 400 mg of active principle to
      administer by slow intravenous perfusion (1 hour) diluted in 5% glucose solution.
      The multicentre study was open and non-comparative. The physician could choose
      between two different dosage schedules to use for surgical prophylaxis. The
      ultrashort schedule consisted of treatment with 2 ampoules (800 mg), given in the
      hour before the operation (followed for 217 cases). The short schedule consisted
      of 2 ampoules (800 mg) given in the hour before the operation, another 2 ampoules
      12 hours after surgery and 2 ampoules 24 hours after the surgery (followed for
      223 cases). The prophylaxis with pefloxacin was effective, with control of the
      temperature, the ESR and wound healing in the post-operative period. The surgical
      wounds of 11.4% of cases (50/440) were erythematous and infiltrated on the 2nd
      day, and of 14.8% of cases (65/440) on the 3rd day, and then became normal on the
      next few days. 24 patients had infections after the operation, in 15 cases
      involving the surgical field (3.4%) and in 9 cases being infections of the
      respiratory or urinary systems.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7808661
TI  - [Nino Masera, 1922-1994].

PMID- 7808662
TI  - [Treatment of traumatic injuries of the spleen. Retrospective analysis of 164
      cases].
AB  - Increased awareness of the spleen's immunologic function and the risk of
      overwhelming post-splenectomy sepsis has aroused interest in methods of splenic
      preservation in patients with abdominal trauma. During an 8-year period, 164
      patients with documented blunt splenic injuries were treated in accordance with
      an evolving therapeutic program. Definitive treatment included nonoperative
      management in 19 patients (group I, 11.6%), repair in 50 (group II, 30.5%) and
      splenectomy in 95 (group III, 57.9%). Mortality and morbidity were higher in
      group III (6.3% and 34.3% respectively) according to the Injury Severity Score
      (ISS 33.3 +/- 13). In group II one patient died from severe head injuries. Only
      one patient failed nonoperative management and required laparotomy with resultant
      splenectomy on hospital day 10. Observation without surgery has proved to be safe
      and effective in children (failure incidence less than 10%); success rates in
      adults would not parallel the experience reported in children because of
      differences in anatomy and mechanism of injury. Selective criteria, including
      hemodynamic stability after initial fluid challenge, normal level of
      consciousness, lack of peritoneal signs, transfusion requirements of less than 4
      units of blood, CT demonstration of minor splenic lesion and exclusion of
      associated abdominal injuries requiring surgery, make eligible for nonoperative
      management 12 to 18% of adults with anticipated success in over 75%. Operative
      repair or partial splenectomy can be employed in many patients, both adults and
      children, with a 1% incidence of rebleeding necessitating reoperation.

PMID- 7808663
TI  - [Pathophysiology of pancreatico-duodenectomy according to Traverso-Longmire.
      Clinical and instrumental study].
AB  - The authors report their experience with 9 patients, affected by pancreatic and
      periampullary carcinoma, treated using pancreaticoduodenectomy with pyloric
      preservation. They analyse the physiopathology of this technique, by the light of
      the international reports, and note the advantages that this technique allows
      about the nutritional status and the quality of life of the patients operated on.

PMID- 7808664
TI  - [Laparoscopic cholecystectomy. Personal experience].
AB  - The authors present their experience (136 cases) in the treatment of
      cholelithiasis with coelioscopic cholecystecomy. After a comparison of this
      modern technique with the traditional laparotomic approach, they underline the
      several advantages of coelioscopy (short hospitalization and early return to
      patient's work, reduced post-operative abdominal pain, avoidance of laparocele,
      better aesthetic results). Then the authors describe the present treatment of
      combined cholecysto-choledochic lithiasis with the help fo ERCP (their hope is
      for further improvement in surgical instruments to allow a single laparoscopic
      solutions.

PMID- 7808665
TI  - [Surgical excision of lung neoplasms in the elderly. Immediate results].
AB  - The authors have analyzed a series of 807 patients who underwent resection for
      Bronchogenic Carcinoma at the "I Istituto di Clinica Chirurgica" of the
      University of Rome "La Sapienza" since 1950. The aim of the search was to
      evaluate the immediate results of surgical treatment in relation to age of the
      patients. Seventy-one patients were < 65 years old, 91 patients were older. The
      incidence of post-operative complications and mortality rate (within the 30th day
      from surgery) was related to the following risk factors: concomitant pulmonary
      and extrapulmonary diseases, cigarette smoking, laboratory values (red blood cell
      count, protein electrophoresis, urea nitrogen, glucose), type of lung resection,
      extent of resection, histology and post-surgical stage. The rates of post
      operative complications and mortality were 34.1% and 27.5% in elderly patients,
      while in younger patients they were respectively 26.3% and 16.2%. In the elderly,
      cigarette smoking, cardiovascular diseases, diabetes, renal failure, type of lung
      resection and extent of resection, were related to an increase of the post
      operative complications and mortality rate. In the younger patients, the extent
      of resection to adjacent structures was the primary risk factor for immediate
      results. Screenings in elderly and early diagnosis represent the strategy to
      allow more conservative surgical treatments and reduction of complications and
      mortality.

PMID- 7808666
TI  - [Extrathoracic surgical emergencies in hospitalized patients with
      bronchopulmonary diseases. Analysis of the operative risk].
AB  - An experience of surgical non-thoracic emergencies in patients admitted for
      chronic lung disease is herein presented. Fifty-four patients out of 10457
      admitted in the four Departments of Pneumology of the Binaghi Hospital (Cagliari)
      between 1-1-1985 and 31-3-1993, were referred to our Department of General
      Surgery due to non-thoracic surgical emergencies. There was a considerable delay
      in the referral (only 25% of patients within 12 hours from the onset of
      symptoms): indeed predominant respiratory symptoms, hypoxia and hypercapnia made
      these patients no responsive to symptoms of surgical emergency. Surgical
      emergencies in causal correlation with respiratory disease (intestinal occlusion
      due to abdominal metastases of lung carcinoma, complicated peptic ulcer) had the
      worst prognosis (mortality: 52.9%). Those in chance connection, such as acute
      limb ischemia and preexisting abdominal disease, had a less adverse outcome.
      Mortality, however, was 37.5%: this datum outlines the role of chronic lung
      disease in defining operative risk. The authors call attention to three groups of
      observed patients: 1) three patients were operated on for intestinal occlusion
      due to unrecognized abdominal neoplasia, that showed itself in the course of
      hospitalization in the Department of Pneumology for lung metastases; 2) in 3
      cases symptoms and signs of acute abdomen were observed without abdominal
      disease. The cause of acute pseudoabdomen was diaphragmatic pleural or basal
      pulmonary inflammation; 3) the eight patients with pulmonary embolism were all
      admitted in the Department of Pneumology with a wrong diagnosis of
      bronchopneumonia.

PMID- 7808667
TI  - [Preoperative and immediate postoperative respiratory therapy in patients with
      pulmonary resection].
AB  - Twenty patients with a resectable lung cancer and with a low respiratory function
      were included in this study. During the preoperative period all patients
      underwent a physiokinesic preparation in view of some improvement of their
      ventilation performances. Methodology as well as results are reported good
      response to the program, better post-operative functional recovery and absence of
      complications were observed in this group of patients.

PMID- 7808668
TI  - [Anatomic and surgical considerations regarding the recurrent laryngeal nerve in
      thyroidectomy].
AB  - The majority of surgeons view the preliminary identification of the recurrent
      laryngeal nerve (RLN) as an essential stage in thyroidectomy in order to preserve
      thyroid integrity. This conviction is based on the fact that the anatomical
      relations of the recurrent nerve during the cervical tract with adjacent
      structures are highly variable. The preparation of the RLN in a series of 42
      thyroidectomies performed by the 1st Department of Pathological Surgery of the
      University of Florence confirmed this variability above all with regard to
      relations with the trachea, Berry's ligament and the branches of the lower
      thyroid artery. As a result, it is justified to consider the identification and
      preliminary preparation of the RLN on both sides as a fundamental and unavoidable
      stage in thyroidectomy.

PMID- 7808669
TI  - [Monitoring of antithrombin III in general surgery].
AB  - The authors studied the effects of surgery on hemocoagulation parameters (PT,
      PTT, PLT, Fibrinogen, AT III). 30 patients, undergoing extrahepatic surgery were
      observed. Measurements were performed before, during and immediately after
      procedure, and 24 hs and 48 hs later. Results showed a significant drop of AT III
      activity (p < 0.05) throughout the surgical procedure with a prompt reversal to
      normal values right after the end of it. Fibrinogen values continuously increased
      from the end of surgery (compared to intra-op values) (p < 0.05) up to 48 hs (p <
      0.01). PTT values decreased at the end of surgery (p < 0.05) and returned to
      normal during the following 24 hs. No thromboembolic and hemorrhagic
      complications were observed during the postoperative phase, with all patients
      being discharged after surgical resolution of pathologies. In conclusion accurate
      monitoring of hemocoagulation parameters (especially AT III) seems to be useful
      in order to prevent thromboembolic and/or hemorrhagic complications during and
      after surgery.

PMID- 7808670
TI  - [Effectiveness of quarterly assessment of CEA, TPA and GICA serum levels in
      gastric and colorectal carcinomas: Prospective study of 174 patients undergoing
      radical surgery].
AB  - One-hundred seventy four consecutive patients who underwent curative resection
      for gastric and colorectal cancer between 1983 and 1985, were studied
      prospectively to evaluate the roles of sequential CEA, TPA and GICA
      determinations and independent clinical examinations, in the early diagnosis of
      resectable recurrences. Sixty-six recurrences (33 from gastric and 33 from
      colorectal cancer) were detected between 6 and 42 months after primary surgery.
      In gastric cancer CEA, TPA and GICA showed a sensitivity of 64%, 73%, and 60%,
      and a specificity of 67%, 65% and 54% respectively. Nine patients (27%) underwent
      surgical treatment for the recurrent disease, and 4 of them (44.4%) had
      resectable recurrence, for a total resectability rate of 12%. Out of these four
      patients, three patients are still living after 12, 36 and 44 months respectively
      from re-operation without evidence of neoplastic disease. In one of these
      patients re-operation was performed on the basis of the elevation of the three
      markers, without any other clinical sign of disease, this patient had a
      resectable solitary hepatic recurrence. In colorectal cancer CEA, TPA and GICA
      showed a sensitivity of 73%, 73%, and 49%, and a specificity of 77%, 87%, and 97%
      respectively. Fourteen patients (42.4%) underwent surgical treatment for the
      recurrent disease, and 8 of them (57%) showed a resectable recurrence, for a
      total resectability rate of 24.2%. Six patients are still living after 9, 16, 21,
      31, 41 and 53 months respectively from reoperation without evidence of neoplastic
      disease.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7808672
TI  - [New surgical technique for the repair of abdominal hernia with mesh].
AB  - The use of prostheses is indispensable in major anterior abdominal hernias when
      it is not possible to close the edges of the hernial opening without strain. The
      most commonly used prostheses are made from dacron, polypropylene (PPNE) and
      expanded polytetrafluoroethylene (EPTF) mesh. It is important to point out that,
      in spite of the excellent characteristics of these materials, there is no ideal
      prosthesis. There is a well-known increase in the risk of rejection and infection
      when mesh is placed in contact with the subcutis and the formation of adhesions,
      with the possibility of occlusions and fistulas, when it is in direct contact
      with the intestine. Whereas EPTF does not cause problems of adhesion, it has a
      greater tendency to cause rejection and infection if placed in the subcutaneous
      area. Moreover, there is a increased risk of displacement and it is also very
      costly. The opposite is true of dacron and PPNE mesh. When the mesh serves to
      "replace" a wall defect and it cannot be isolated by the interposition of the
      peritoneum or muscular fascia, it comes into direct contact with the intestine
      and subcutaneous tissue. The technique outlined here aims to isolate the
      prosthesis from the intestinal loops and subcutaneous tissue. The hernial sac
      itself is used for this purpose and is divided into two flaps by a cut
      perpendicular to the wall. The free edge of one flap is sutured to the inside of
      the hernial opening. The mesh is then sutured half inside and half outside the
      hernial opening.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7808671
TI  - [The use of polypropylene (Marlex) mesh in ambulatory care of inguinal hernia].
AB  - The use of Marlex mesh in the treatment of inguinal hernia produces a series of
      advantages, if compared with traditional techniques. According to the authors,
      these advantages can be identified with the ambulatorial treatment of this
      pathology, with the possibility to use the local anaesthetic, with a minimum
      postoperating pain, with a possible collaboration of the patients with the
      surgeon during the operation, and with a considerable reduction of relapses. The
      authors explain the different steps of their techniques.

PMID- 7808673
TI  - [Idiopathic unilateral hypoplasia of the breast].
AB  - Unilateral hypoplastic breast is a rare anomaly. The correction of the asymmetry
      is usually achieved by the use of breast implants or breast expanders. Sometimes
      the controlateral breast must be modified to gain a good symmetry.

PMID- 7808674
TI  - [Vesico-vaginal fistula after abdominal hysterectomy. Use of the Legueu
      technique].
AB  - Vesicovaginal fistulas are commonly seen as a complication of abdominal (or
      vaginal) Hysterectomy. The signs and symptoms of a vesicovaginal fistula depend
      upon its size and location. Identification of a vesicovaginal fistula includes an
      intravenous urogram; cystoscopy may be performed in order to evaluate the
      possibility of immediate or delayed repair. Case report. Principles of surgical
      repair. The principles of surgical closure are similar: 1) total separation of
      the tissues comprising the wall of the vagina and the wall of the bladder; 2)
      sharp excision of the fistulous tract between to two structures; 3) closure of
      the defects with non-overlapping suture lines; 4) where possible, interposition
      of alternative tissue between the two suture lines. The intervention proposed by
      Legueu allows an abdominal transperitoneal approach to the fistula and is
      comprehensive of these principles. With such a procedure we have treated
      successfully two cases which required surgical closure. CONCLUSIONS. In patients
      who develop vesicovaginal fistulas as a complication of abdominal hysterectomy,
      we have applied the intervention proposed be Legueu, which allows closure of the
      fistula via a transperitoneal route. Preliminar diagnostic evaluation and
      following of the foundamental principles of correct surgical closure are
      indispensable to accomplish a successful intervention.

PMID- 7808675
TI  - [Postoperative lavage. Experimental study of the use of antiseptic solutions].
AB  - The authors report their experience of surgical infections and particularly
      peritoneal intraoperative lavage. In a previous study they have standardized the
      technique. In this study they report on the lavage adding antiseptic substances
      in the solution. The experimental, controlled study, was carried out on Wistar
      rat stock, which were submitted to median laparotomy through which was injected a
      standard bacterial dose composed of 5 bn E. Coli. The peritoneal cavity was
      washed out after a few minutes with physiological solution with clorhexidine or
      PVPI dissolved. The main results were an increase of aderential syndrome and a
      less survival percent age (physiological solution = 100%, clorhexidine = 60%,
      iodophors = 23%). The authors concluded by pointing out that the use of
      antiseptic peritoneal lavage solution is a method that should be proscribed from
      operating rooms because it is unnecessary and detrimental to health.

PMID- 7808676
TI  - ["Prophylactic" video-laparoscopic cholecystectomy].
AB  - The authors examine the prophylaxis of infections caused by cholelithiasis in
      kidney and heart transplant candidates as a new indication for videolaparoscopic
      cholecystectomy (VLC). The study included 6 patients in dialysis for chronic
      renal insufficiency and one patient suffering from cyanogenic congenital
      cardiopathy with asymptomatic gallbladder calculosis. The results obtained show
      that there are no substantial differences compared to patients without associated
      pathologies and justifies the inclusion of "prophylactic" VLC in preparatory
      treatment protocols for kidney and heart transplant in patients suffering from
      cholelithiasis. The authors emphasise the necessary technical measures to prevent
      hemorrhage, intraoperative loss of CO2 and postoperative laparoceles.

PMID- 7808677
TI  - [Solitary gastric plasmacytoma. Case report and review of the literature].
AB  - The authors report a case of extramedullary gastric plasmacytoma followed from
      the clinical onset of the disease until the death of the patient. The literature
      on this topic was reviewed. The male patient underwent total gastrectomy with
      left splenopancreatectomy when he was 40 years old; after surgery followed by
      adjuvant chemotherapy and radiotherapy, the plasmacytoma relapsed; the patient
      died 4 years after the first operation. Gastric plasmocytoma is a rare
      pathological entity; different postsurgical therapeutical approaches are derived
      from the inclusion of this gastric neoplasm in the lymphomas or in the
      extramedullary plasmacytomas. The authors emphasize a better response of the
      disease to adjuvant chemotherapy than to radiotherapy after surgery. it suggests
      the necessity of a separation of gastric plasmacytomas from the other gastric
      lymphomas.

PMID- 7808678
TI  - [Gastric leiomyosarcoma. Three clinical cases in emergency].
AB  - The authors describe three cases of gastric leiomyosarcoma that required surgical
      treatment in emergency. Myogenic gastric tumors are extremely rare (1-3% of
      primitive gastric neoplasias) and little is known about their biological
      evolution, even if they seem to have scarce power of spreading and of local
      invasion. Echoendoscopy appears to be the best screening method for the
      evaluation of staging and DT (doubling time). In the authors' opinion, when
      neoplasms have a diameter less than 5 cm, subtotal or total gastrectomies don't
      offer better results in the follow-up than simple minimal excision of the gastric
      tumor.

PMID- 7808679
TI  - [Acute abdomen secondary to autoimmune vasculitis in systemic lupus
      erythematosus. Case report].
AB  - The authors report the case of a female patient suffering from systemic lupus
      erythematosus who was referred to their attention with symptoms of acute abdomen
      due to gangrenous appendicitis following autoimmune vasculitis.

PMID- 7808680
TI  - Efficacy comparison of glutaraldehyde-phenate vs other glutaraldehydes in fomites
      disinfection, by different methods.
AB  - OBJECTIVE: To compare the efficacy of glutaraldehyde-phenate against four other
      glutaraldehydes. DESIGN: We use two methods: (1) Bacteriostatic method- With 97
      microrganisms of 8 different species. (2) Bactericide method- With a low
      contamination (10(4)cfu) plus organic soil (simulating the work conditions of
      glutaraldehyde when we wash fomites before disinfection), we used six
      microorganisms (the most sensitive and the most resistant, according to the first
      method, of three species: P. aeruginosa, R. pneumoniae and S. aureus) in
      different times and concentrations. RESULTS: Glutaraldehyde-phenate is the most
      active against Gram-positives, but less with Gram-negatives. However when we
      study the total effect of the five glutaraldehydes, there are no significant
      differences among the mean of the minimum inhibitory concentrations (MICm). With
      the bactericide method the total bactericide effect (0% survival) is easily
      achieved with the five glutaraldehydes at 2% dilution, but when we reduced the
      concentration (1/16) we needed 60 minutes for glutaraldehyde-phenate and 15-30
      minutes with the rest. CONCLUSIONS: The five products have got a similar efficacy
      in higher concentration, but at 1/16 dilution glutaraldehyde-phenate need
      increase the contact-time on the fomite.

PMID- 7808681
TI  - [Leukocyte procoagulant activity and chemotherapeutic agents: comparison between
      the effects of adriamycin and epiadriamycin on the procoagulant lympho/monocytic
      activity in vitro].
AB  - It is well known that a number of antineoplastic agents are able to induce
      procoagulant cellular activity and tissue factor not only in neoplastic cells but
      also in normal, monocyte/macrophage cells, and some of them, including
      adriamycin, even increase procoagulating activity of the factor already
      expressed, providing a further example of the possible co-participation of
      chemotherapy in the onset of thrombotic complication in cancer patient.
      Epirubicin is an analogue of adriamycin but differs strikingly in terms of its
      collateral effect, in particular being less cardiotoxic. To the authors'
      knowledge there are no data regarding the possible effect of epirubicin on
      lympho/monocyte procoagulant activity. This study shows that not only adriamycin
      but also epirubicin is able to increment the level of lympho/monocyte
      procoagulant activity "in vitro", with a dose-dependent effect, and to synergize
      with bacterial endotoxin in increasing this leukocyte activity, although the
      effect is significantly greater in the case of adriamycin. The importance of
      these findings at practical and clinical level remains to be defined, in
      particular in the length of the different pharmacokinetic behavior of these two
      chemotherapeutic agents and in the context of those neoplastic diseases for which
      adriamycin and Epirubicin treatment is most frequently used.

PMID- 7808682
TI  - [Parma stroke data bank: atherothrombotic and lacunar stroke].
AB  - In an epidemiological research about stroke, we studied 235 patients with
      atherothrombotic brain infarctions and 81 patients with lacunes. It was a
      longitudinal study concerning patients admitted to our Medical Division during
      the acute phase and followed up for one year after the onset. We report some
      anamnestic data, the frequency of positive brain CT scan, main risk factors,
      symptoms at the onset, severity degree of the stroke within the first 72 hours,
      complications during, and outcome after, the first four weeks, including personal
      performances and environmental fitness, mortality rate and frequency of relapses.
      We also report some of these data after one year from the acute episode.

PMID- 7808683
TI  - [Intrahepatic cholestasis caused by biochemical errors of bile acids. Part I -
      Nosographic, pathogenetic, diagnostic features].
AB  - Intrahepatic cholestasis occurs in certain conditions characterized by a
      biochemical error of bile acid metabolism, resulting from a disorder of the
      hepatic canalicular system responsible for synthesis or secretion of the bile
      acids. As regards the pathogenesis of these "primary" forms of cholestasis, it
      must be remembered that cholestasis represents the outcome of various factors
      capable of interfering with the mechanism of bile flow. Therefore the factors
      known to be involved in cholestasis, such as the metabolic steps in bile acid
      metabolism, the cytoplasmic membrane, the mitochondria, the cytoskeleton of the
      liver cell, the intercellular junctions, the physicochemical state of the
      canalicular bile, are discussed briefly. The diagnostic and clinical aspects of
      cholestasis with reference to the clinical symptoms, laboratory findings and to
      role of liver biopsy are synthesized, and the essential criteria for a
      methodological approach to cholestasis are proposed.

PMID- 7808684
TI  - [Hasharon hemoglobinopathy in a family].
AB  - The authors describe an 18 year old athlete, a carrier of Hasharon
      haemoglobinopathy, pathology which had been checked in some ascendants too. Such
      a haemoglobinopathy, which has at first been verified in Ashkenazy Hebrew people
      and is nowadays rather common in North East Italy, shows clinical and laboratory
      features which are slightly or not at all mentioned in the literature. The
      leading reference point in the disease's development is the connection between
      splenomegaly and repetitive low erythrocytosis with serum iron deficiency and
      increase of the reticulocyte number. The same laboratory data had been observed
      in his father and in his paternal grandmother; both of them proved to te
      heterozygous carriers of Hasharon haemoglobinopathy. In all cases we caught the
      diagnostic validation by the means of isoelectrophoresis involving haemoglobin
      lysate in polyacrylamide gel. The authors think that the Hasharon shape they
      verified may be a variant of the classic phenotype: the splenomegaly and
      erythrocytosis may signify a brisk and primitive erythropoiesis with increasing
      reticulocytes, which might compensate for the anomalous synthesis of the alpha
      chains. Serum iron deficiency may signify an increase of the iron consumption.
      Moreover, the authors do not exclude the possibility of further associational
      abnormalities.

PMID- 7808685
TI  - [A clinical case of demyelinating disease with basilar impression].
AB  - The authors report a clinical case of a 48-year-old female patient admitted to
      the Neurological Division following acute symptoms characterised by generalised
      asthenia, motory disorders (incoordination, equilibrium or gait deficit)
      accompanied by diplopia. Instrumental (medullary and encephalic NMR) and
      laboratory tests revealed a malformation of the atlo-occpital hinge with basilar
      impression and areas of corticosubcortical demyelinisation signifying multiple
      sclerosis. The liquor test was also positive for the presence of oligoclonal
      bands of IgG with a Link index of 0.97 (lower v.n. at 0.7). The association
      between these two pathologies is rare, whereas the need for a differential
      diagnosis between them often arises. Therefore, two pathologies which are
      mutually exclusive in many cases were present in an associated form in this case.

PMID- 7808686
TI  - [Neoplastic pericarditis secondary to ovarian adenocarcinoma. Report of a
      clinical case].
AB  - The pericardial metastatic disease is rare in genital cancers but is frequent in
      all other cancer. The authors report the case of a female affected by both
      papillary ovarian cancer and pericardial metastatic disease. Carcinomatous
      pericarditis began with cardiac tamponade. This pericarditis is very rare during
      ovarian cancer and there is little informations in the literature about it. The
      clinical picture showed an acuteness that cleared up with many pericardial
      tapping paracenteses, and after six cycles of polychemotherapy we obtained the
      disappearance of pericardial effusion and metastasis with total disappearance of
      abdominal metastases and the total remission of the cancer.

PMID- 7808687
TI  - Hemophiliac class action suit.

PMID- 7808688
TI  - Reflections of the charter class at New Jersey Medical School.
AB  - In 1954, New Jersey Medical School opened; the charter class matriculated in
      September 1956. The members of the class went on to varied paths in the medical
      profession. Two charter class members reflect on the chance to be a part of the
      beginnings of medical education in New Jersey.

PMID- 7808689
TI  - New Jersey research: frontiers of hepatology.
AB  - Diagnostic criteria and prognosis have been revised for patients with liver and
      biliary tract diseases. This information provides an improved knowledge base for
      new preventive measures, therapeutic modalities, and outcome research at UMDNJ
      New Jersey Medical School Liver Center.

PMID- 7808690
TI  - The founding and development of New Jersey Medical School.
AB  - The need to address the social and biological aspects of medicine was emphasized
      at the founding of New Jersey Medical School in 1954. This need has remained a
      major goal, as the sponsorship, name, and location of the Medical School have
      changed with the times.

PMID- 7808692
TI  - Shock, sepsis, and the gut.
AB  - The fact that bacteria are translocated from the gut to the blood stream and
      organs immediately following hemorrhagic shock in humans has been established.
      What role this phenomenon has on sepsis still is under evaluation. The author
      reviews current research at UMDNJ-New Jersey Medical School.

PMID- 7808691
TI  - Diabetic cardiomyopathy: experimental and clinical observations.
AB  - Heart failure, arrhythmia, or chest pain can be a consequence of diabetes
      independent of coronary disease or hypertension. Diastolic myocardial dysfunction
      is common, contributing to the high mortality during acute infarction. The
      authors discuss diabetic cardiomyopathy and its management.

PMID- 7808693
TI  - Molecular genetics and human disease.
AB  - Through the advancements of molecular genetics, physicians and researchers are in
      an extraordinary period of study concerning the molecular basis of medicine. The
      author discusses recent developments in the identification, isolation, and
      manipulation of genes.

PMID- 7808694
TI  - Sclerosing basal cell carcinoma: management with electron beam therapy.
AB  - There are two types of sclerosing basal cell carcinoma (BCC), one entirely with
      this histology and a second with a prominent sclerosing component. Sclerosing BCC
      and nodular BCC with a sclerosing component often represent a difficult
      diagnostic and therapeutic challenge.

PMID- 7808695
TI  - Neurochemical organization of circadian rhythm in the suprachiasmatic nucleus.
AB  - The circadian rhythm in mammals is under control of the pacemaker located in the
      suprachiasmatic nucleus (SCN) of the hypothalamus. This tiny nucleus contains a
      number of neurochemicals, including peptides, amines and amino acids.
      Heterogeneous distribution of these neurochemicals defines the substructures of
      the SCN. In the present review, functional significance of such neurochemical
      heterogeneity in the SCN is discussed in the light of circadian patterns of the
      concentrations of these neurochemicals in the SCN and their effects on SCN
      neurons in in vitro slice preparation. In particular, the hypothesis that the
      dorsomedial SCN is involved in maintaining the circadian rhythm, while the
      ventrolateral SCN is involved in adjusting the phase of the rhythm, is critically
      discussed. These considerations suggest that distinct sub-components of the SCN
      as marked by neurochemicals, interact with each other and this organizational
      architecture could be the basis of the proper operation of the circadian time
      keeping system in this nucleus.

PMID- 7808696
TI  - Latexin: a molecular marker for regional specification in the neocortex.
AB  - It largely remains to be elucidated how the mammalian neocortex is regionally
      specified during development. In an attempt to obtain molecular markers in the
      neocortex, we have generated a monoclonal antibody PC3.1 which recognizes a
      subset of neurons located in lateral, but not dorsal, neocortical areas. The
      antigen is a novel class of protein, named latexin, having a molecular weight of
      29,000. Our in vitro studies have revealed that the neocortical regional
      specification for the production of latexin-positive neurons occurs very early
      prior to thalamocortical interactions and the completion of neurogenesis,
      indicating that elements intrinsic to the neocortex play important roles in the
      neocortical specification. Furthermore, our recent analyses have suggested that
      this regional specification is attributable, at least in part, to an early
      restriction of developmental potential in neocortical progenitor cells to become
      latexin-positive neurons.

PMID- 7808697
TI  - Neuronal activity in the primate supplementary, pre-supplementary and premotor
      cortex during externally and internally instructed sequential movements.
AB  - This study recorded the activity of neurons in the (i) supplementary motor area
      (SMA), (ii) pre-SMA (the motor area immediately rostral to the SMA), (iii)
      premotor cortex (PMC) and (iv) primary motor cortex (MI), while the monkey
      performed a conditional sequential motor task that ensures sequencing of multiple
      movements to the same manipulandum. This paradigm was chosen in order to prevent
      the participation of spatial cues in prompting the correct motor sequence. Three
      different movements (turn-push-pull) were performed under two task conditions:
      (i) internally determined (I): the monkey had to generate a pre-determined
      sequence from memory and without visual guidance; (ii) externally triggered (E):
      the correct sequence of movements was performed by following lights illuminated
      one after the other. Neuronal activity during the following periods were
      analyzed: instruction (300 ms following the onset of the auditory instruction
      signal); delay (interval between the end of the instruction period or the
      termination of the previous movement and the movement trigger); premovement
      (interval between the trigger signal and the movement onset); movement (interval
      between the mechanically-sensed movement onset and the completion of the
      movement) and reward (500 ms period centered at the time of reward delivery). Pre
      SMA neurons were generally more active during the delay and premovement as
      compared to the movement, instruction and reward periods. Activity in the pre-SMA
      was more related to E during the pre-movement period, but exhibited a
      preferential relationship to I in the movement period. SMA neurons were more
      active when the sequential motor task was internally generated.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7808698
TI  - Sprouting of CA3 pyramidal neurons to the dentate gyrus in rat hippocampal
      organotypic cultures.
AB  - The understanding of the mechanisms of a functional synaptic plasticity in the
      hippocampus has been expanded greatly by the use of in vitro slice preparations.
      The question addressed in the present study was whether morphological plasticity
      observed in vivo can also be reproduced in hippocampal slices. In vivo,
      hippocampal commissural and association fibers are known to sprout and occupy
      synaptic sites vacated by deafferentation of the dentate gyrus (DG). In
      hippocampal slice preparations, the major input to the DG is eliminated, so that
      the DG is deafferented. Might intrinsic neurons sprout to the DG if the slice
      preparation is maintained for weeks? In this study hippocampal slices obtained
      from 6-day-old rats were cultured. Stimulation of the dentate stratum moleculare
      produced antidromic field potentials in the CA3 of the slices cultivated for more
      than 1 week. The antidromic response was not observed in CA1 pyramidal neurons.
      The CA3 to DG projection response was also observed in a CA3 mini-slice placed
      near a co-cultured whole hippocampal slice, when the DG in the latter was
      stimulated. Moreover, stimulation of the CA3 mini-slice induced synaptic
      responses in the DG of the whole-slice. The conclusion drawn is that
      deafferentation could induce axonal sprouting in a neuron-specific manner in
      hippocampal organotypic culture. This preparation would be potentially useful for
      the screening of chemical factors that influence sprouting of central neurons.

PMID- 7808699
TI  - Somatosensory evoked magnetic fields following median nerve stimulation.
AB  - Topography of somatosensory evoked magnetic fields (SEFs) following stimulation
      of the median nerve were investigated in normal subjects. N20m-P30m-N40m-P60m and
      their counterpart, P20m-N30m-P40m-N60m, were identified in the hemisphere
      contralateral to the stimulated median nerve. Their equivalent current dipoles
      (ECDs) were considered to be located in the hand area of area 3b in the primary
      sensory cortex (SI). Restricted deflections, P25m and N25m, were considered to be
      generated in area 1 in SI. Therefore, short-latency deflections less than 40 ms
      were considered to be hybrids of ECDs generated in areas 3b and 1. Middle-latency
      deflections, N90m-P90m, were considered to be generated in the second sensory
      cortex (SII), but they were greatly affected by the much stronger fields
      generated in SI. The N30m deflection, which was a magnetic reflection of the N30
      potential of somatosensory evoked potentials (SEPs), were widely recorded in the
      frontal area. The generator site of N30 of SEPs is considered to be the
      supplementary motor area (SMA). However, ECDs of N30m were located in SI, and no
      significant ECD generated in the frontal area including SMA was detected. No
      significant deflections other than small N90m-P90m in SII were identified in the
      hemisphere ipsilateral to the stimulated nerve. No significant deflections whose
      ECDs were generated in the mid-parietal area were identified. In conclusion,
      short- and middle-latency SEFs are mainly generated in area 3b in SI
      contralateral to the stimulated median nerve, and responses generated in area 1
      of SI and SII affect the SEFs to some degree.

PMID- 7808700
TI  - Rapidly proliferating glial cells isolated from adult mouse brain have a
      differentiative capacity in response to cyclic AMP.
AB  - A glial cell line designated as B2 was generated from primary cultures of
      oligodendrocytes/astrocytes isolated from an adult BALB/c mouse brain and
      maintained for over 1 year. Phenotypic characteristics of B2 cells were
      investigated by immunolabeling with cell type-specific markers for
      oligodendrocytes (O4 and galactocerebroside (GalC)), astrocytes (glial fibrillary
      acidic protein (GFAP)), and immature neuroectodermal cells (vimentin). When
      cultured in a serum-containing medium, B2 cells exhibited a bipolar or a tripolar
      process-bearing morphology and proliferated with a 24-28 h doubling time, without
      requirement of exogenous growth factors. Under this culture condition, vimentin
      was identified in all of the B2 cells, GFAP in 7%, and O4 and GalC in less than
      1% of the cells. When cultured in a serum-free medium containing 1 mM dibutyryl
      cyclic AMP (dbcAMP), B2 cells extended longer processes and 45% of the cells
      expressed cell type-specific markers for oligodendrocytes or astrocytes. GFAP was
      identified in 29% of B2 cells, O4 in 16%, and GalC in 6% of the cells, although,
      neither O4+GFAP+ nor GalC+GFAP+ cells were observed. B2 cells proliferated in
      response to phorbol 12-myristate 13-acetate (PMA), basic fibroblast growth factor
      (bFGF), insulin, insulin-like growth factor (IGF-I) and platelet-derived growth
      factor (PDGF), but not to dbcAMP, forskolin (FK), or retinoic acid (RA). These
      results indicate that B2 cells are distinct from typical oligodendrocytes and
      astrocytes with respect to their great proliferative potential, and suggest that
      B2 cells, with a capacity to differentiate into oligodendrocytes and astrocytes
      in response to cyclic AMP, may represent a population of glial precursor cells in
      the adult mouse central nervous system (CNS).

PMID- 7808701
TI  - Differences in serum interleukin-6 (IL-6) between healthy dextral and non-dextral
      subjects.
AB  - Serum interleukin-6 (IL-6) was measured in picograms/ml pg/ml using an
      immunoassay (ELISA) in healthy individuals (n = 148), of whom 128 were classified
      as dextral and 20 as non-dextral, as per a laterality questionnaire. Only 3 (15%)
      non-dextral individuals had serum IL-6 levels above the lower limit of the assay
      sensitivity as compared to 59 (46%) of dextral individuals (P < 0.013). There
      were no significant correlations between previously determined mitogen stimulated
      interleukin-2 production and autoantibodies in a subset of the same individuals.
      While this data does not provide casual information, it adds to the evidence of
      the asymmetric regulation of immune functions by the cerebral hemispheres.

PMID- 7808702
TI  - Immunohistochemical double-labeling study of gonadotropin-releasing hormone
      (GnRH)-immunoreactive cells and oxytocin-immunoreactive cells in the preoptic
      area of the dwarf gourami, Colisa lalia.
AB  - The distribution of gonadotropin-releasing hormone (GnRH)-immunoreactive (ir)
      cells in the preoptic area (POA) of the dwarf gourami, Colisa lalia, was
      immunohistochemically studied. These neurons form cell columns on both sides of
      the common ventricle, and their axons project to the pituitary gland by forming
      distinct bundles. Also examined was the distribution of isotocin (IST) cells in
      the POA by using an anti-oxytocin (OXT) serum which has been proven to crossreact
      with IST. These two kinds of immunoreactive cells were distributed quite
      similarly in the POA. However, by using an immunofluorescence double-labeling
      method on thinner sections we found that a population of small IST cells in the
      ventral POA were also immunoreactive to GnRH, but that large IST cells in the
      dorsal POA were not immunoreactive to GnRH, and small GnRH-ir cells in the most
      ventral POA were not immunoreactive to the OXT antiserum. In the pituitary gland,
      GnRH-ir fibers were found in both the neurohypophysis and proximal pars distalis,
      but IST fibers were found only in the neurohypophysis.

PMID- 7808703
TI  - Meaning and mystery in nursing science and art.

PMID- 7808704
TI  - A vision of nursing research priorities.

PMID- 7808705
TI  - Levine's conservation model as a guide to nursing practice.

PMID- 7808706
TI  - Laughing and health: a study using Parse's research method.
AB  - The purpose of this research was to uncover a structure of the lived experience
      of laughing and health using Parse's research method. Twenty men and women over
      65 years of age volunteered to participate in the study. The structure of the
      lived experience of laughing and health was found to be a potent buoyant vitality
      sparked through mirthful engagements, prompting an unburdening delight deflecting
      disheartenments while emerging with blissful contentment. Recommendations for
      further research and practice are suggested.

PMID- 7808707
TI  - King's theory in practice with elders.
AB  - This article discusses the utilization of Imogene M. King's (1981) theory of goal
      attainment with a group of elderly clients who were living in a nursing home and
      experiencing many of the chronic health problems frequently associated with
      advanced age. Group members met weekly for 10 weeks to explore methods to promote
      continuous health restoration. Application of King's theory of goal attainment,
      utilizing interactions, transactions, perceptions, and expressions of self,
      facilitated mutual nurse-client goal identification and achievement.

PMID- 7808708
TI  - The meaning of being a senior: phenomenological research and interpretation with
      Parse's theory of nursing.
AB  - The purpose of this article is to report findings from a phenomenological
      analysis on the meaning of being a senior. Six hundred narrative stories written
      by older Canadians on their personal experiences in later life were analyzed
      using the operations of the van Kaam phenomenological method. Seven common
      elements were created to capture the shared meaning about being a senior
      contained in the narratives. The seven elements when linked together formed the
      central finding of the study in a structural definition. The structural
      definition arising in this study is: Being a senior means engaging the now while
      rolling with the vicissitudes of life as refined astuteness surfaces a buoyant
      unburdening. It is as though shifting rhythms propel discovery through grateful
      abiding in wondering awareness as anticipation of new possibles enlivens
      connectedness and altruistic commitments affirm self amidst the retrospective
      pondering of everydayness. This definition was interpreted from Parse's
      theoretical perspective in order to expand the knowledge base of nursing science.
      Descriptive expressions from the narratives were linked with major concepts from
      Parse's theory. Implications for research and practice are specified. Discussion
      includes comparison of the findings with other qualitative investigations
      exploring the meaning of aging with older persons in the United States, Germany,
      Britain, and Nepal.

PMID- 7808709
TI  - Using Roy's adaptation model in practice: nurses' perspectives.
AB  - Using a qualitative research methodology, the utility of the Roy adaptation model
      as a framework for nursing practice within a hospital setting was investigated.
      The level of integration of the model into practice varied among nurses. The
      model was generally found to be useful in focusing, organizing, and directing
      nurses' thoughts and actions regarding patient care, resulting in a perception of
      improved quality of nursing process and patient outcomes. Prior education on the
      Roy model and participation in professional advancement activities facilitated
      model integration, while lack of education and resistance to change inhibited
      implementation of model-based practice.

PMID- 7808711
TI  - Nursing's agenda of health care reform: regressive or advanced-discipline status?

PMID- 7808710
TI  - Choosing life goals: a phenomenological study.
AB  - The purpose of this phenomenological study was to uncover the meaning of the
      lived experience of choosing life goals. Seven married women, nurse
      administrators between the ages of 27-37, employed in middle management positions
      in two large metropolitan hospitals, were asked to provide a written description
      of a situation in which they found themselves choosing life goals. Giorgi's
      (1975) qualitative method of phenomenology was used to analyze the written
      descriptions. The major finding of this study was choosing life goals is
      struggling to fulfill competing ambitions while experiencing paradoxical feelings
      of calmness-turmoil, success-defeat, and security-insecurity in the process of
      affirming cherished beliefs. Findings from this study support the value of the
      phenomenological method for nursing research and enhance the knowledge base of
      nursing by expanding Parse's theory of human becoming. Findings reveal the
      importance of understanding more fully the processes of choosing life goals and
      how choices reflect health.

PMID- 7808712
TI  - A confusing issue.

PMID- 7808714
TI  - The DSSNY response to managed care programs.

PMID- 7808713
TI  - HIV status and confidentiality laws.

PMID- 7808715
TI  - New concepts in restorative dentistry. The CEREC CAD/CAM system.
AB  - The CEREC system offers the dentist a conservative means to esthetically restore
      posterior teeth in a single patient visit. It uses advanced restorative
      materials. It does not require traditional impression techniques, temporaries or
      outside laboratories. Seven-year recalls in Europe and five-year recalls in the
      United States establish a firm basis for predicting continued clinical success of
      these restorations. The technology is currently being taught in 13 dental schools
      in the United States. Four schools are continuing clinical research.

PMID- 7808716
TI  - Managing your personal finances.
AB  - Even a volatile market can be harnessed if the investor has a game plan. Some
      simple guidelines to get you started.

PMID- 7808717
TI  - Hospital dentistry. Window on total family health care.
AB  - A confused and complicated medical history reported by the patient may signal the
      need for additional medical treatment and behavioral counseling. The issue of
      dentistry as a primary care health profession is explored, and two cases are
      presented to illustrate this principle in action.

PMID- 7808718
TI  - Maxillary odontogenic myxoma. A case report.
AB  - The odontogenic myxoma, a slow-growing, benign but often recurrent tumor, is
      unpredictable. The case presented here demonstrates the difficulty of choosing an
      appropriate treatment plan.

PMID- 7808719
TI  - On health care--the costs of its provision.

PMID- 7808720
TI  - Superior orbital fissure syndrome. Secondary to infected dentigerous cyst of the
      maxillary sinus.
AB  - Superior orbital fissure syndrome is a rare condition that presents itself as
      gross and persistent edema of the periorbital tissues, proptosis, subconjunctival
      ecchymosis, ptosis, ophthalmoplegia, dilation of the pupil, absence of direct
      light reflex and presence of consensual light reflex. The corneal reflex is lost,
      sensation is diminished over the forehead, and it is possible that the dimensions
      of the superior orbital fissure are reduced. Infection, however, is not often
      reported as the etiology. The case presented here describes an unusual occurrence
      of superior orbital fissure syndrome secondary to an infected dentigerous cyst of
      the maxillary sinus and its management.

PMID- 7808721
TI  - Article 81 and the dentist.

PMID- 7808722
TI  - Anatomical studies on the extensor carpi radialis longus and brevis muscles in
      Japanese.
AB  - In order to determine whether the muscle bellies of the extensor carpi radialis
      longus and brevis (including additional slips) show laminar disposition, they
      were observed in 490 upper limbs of 245 Japanese cadavers. The author examined
      them from the point of view of lamination of the muscle slips (bellies) and
      classified them into 22 types in this study. The extensor carpi radialis longus
      muscle consists of five layers (A, B, C, D and E). Their proximal portions are
      disposed from radial deep to ulnar superficial as A, B, C, D and E, and the
      distal portions from ulnar deep to radial superficial as A, B, C, D and E. C is
      the main part of the extensor carpi radialis longus muscle, and A, B, D and E are
      additional (accessory) slips. The main part (C) is inserted into the second
      metacarpal bone A and B cross beneath the main part (C) to the ulnar side of the
      hand and are inserted into the third to second metacarpal bones. D and E pass
      across on the main part (C) to the radial side of the hand and are inserted into
      the second to first metacarpal bones. The extensor carpi radialis brevis consists
      of three layers (X, Y and Z). Their proximal portions are disposed from radial
      deep to ulnar superficial as X, Y and Z, and the distal portions from ulnar deep
      to radial superficial as X, Y and Z. Y is the main part of the extensor carpi
      radialis brevis muscle, and X and Z are additional (accessory) slips. The main
      part (Y) is inserted into the third metacarpal bone. X passes deep to Y to the
      ulnar side of the hand and is inserted into the fourth or third metacarpal bone.
      Z passes superficial to Y to the radial side of the hand and is inserted into the
      third or second metacarpal bone. The extensor carpi radialis longus muscle showed
      the normal form (C only present) in 326 of 490 cases, and had the main part (C)
      and one to three additional slips (A, B, D, E) in 164. The extensor carpi
      radialis brevis showed the normal form (Y only present) in 389, and had the main
      part (Y) and one or two accessory slips (X, Z) in 101 of 490 cases.

PMID- 7808723
TI  - Development of cleavage line patterns in the skin of the ovine fetus.
AB  - In fifty six ovine fetuses of both sexes, ranging in length from 20 mm to 41 cm
      crown-rump length, the developmental features of the cleavage lines of the skin
      over the whole body were examined by the stab-wound method using a metal probe
      with a sharp conical point. 1). Cleavage lines were observed as early as the 20
      mm fetal stage. During each fetal stage, the various regions and areas of the
      ovine body were represented by individual cleavage line patterns. 2). The
      cleavage line patterns changed as the occurred the various structures elongated
      or thickened during fetal growth. 3). Among the fetuses, similar cleavage line
      patterns recurred in particular regions or areas, e.g., the flank, the
      antebrachium, the crus and fore- and hind-digits. 4). This recurrence of cleavage
      line patterns reflected the alterations with occurred with the growth of the
      whole body, in accord with the so-called functional-morphological rhythm of
      development.

PMID- 7808724
TI  - Scanning electron microscopy of the organelles of rat incisor odontoblasts--in
      particular the tubulo-vesicular elements.
AB  - The fine structure of rat odontoblasts (OBs) showing the developmental sequence
      of cellular maturation along the long axis of the incisor was studied. The
      cytomorphological changes and relationships of the intracellular components,
      particularly the membranous component, were investigated mainly by scanning
      electron microscopy (SEM) using the AODO (A: aldehyde prefixation; O: osmium
      tetroxide postfixation; D: dimethyl sulfoxide (DMSO) freeze-fracture; O: osmium
      tetroxide maceration) method and transmission electron microscopy (TEM) using the
      conventional methods. The following results were obtained: 1) The elongated young
      OBs were highly polarized and characterized by well-developed concentric
      cisternal granular (rough) endoplasmic reticulum (rER) layers and Golgi complex.
      SEM showed the rER was continuous to the agranular (smooth) ER (sER). 2)
      Transformation of the concentric rER to a tubular network was closely related to
      the maturation and secretory activity of the OBs. 3) Many branched and elongated
      tubular mitochondria were observed in the supranuclear region of young OBs. On
      the other hand, many round-to-ovoid mitochondria were observed particularly in
      the distal clear area of old OBs. 4) SEM also revealed tubulo-vesicular elements,
      which are believed to be structures relating to secretory and absorptive
      functions, composed of secretory granules and small tubules, having connections
      with the cell membrane in both young and old OBs. Furthermore, the small tubules
      were continuous with the larger sER tubules in the distal clear area and cell
      process of the OBs. 5) Using TEM, long lysosomes, various cytosomes and
      multivesicular bodies (MVBs) were usually observed in the peripheral region and
      in the distal cytoplasm and major processes of the OBs. The present SEM and TEM
      studies indicated the MVBs were closely associated with sER tubules of the tubulo
      vesicular elements. 6) Both TEM and SEM showed cytosegresomes containing
      laminated ER and other organelles particularly in the distal clear area of old
      OBs. 7) SEM also showed some thin lateral branchings of the OBs running along the
      fine matricial fibrils, as well as matrix-vesicle-like structures deeply
      invaginated at the basal portion of the cell processes and distributed in the
      predentine. The present morphological study demonstrated a three-dimensional
      configuration of the structures relating to secretory and absorptive functions of
      young and old OBs.

PMID- 7808725
TI  - The true nature of the adductor brevis dually innervated by the anterior and
      posterior branches of the obturator nerve in humans.
AB  - To clarify the true nature and the mechanism of the human adductor brevis
      (specific adductor brevis, SAB) innervated dually by the anterior and posterior
      branches of the obturator nerve, we have carried out gross anatomical examination
      of 100 body halves of 50 adult Japanese cadavers. The SAB was found in 23 of the
      100 thighs (23.0%), and its anterior and posterior surfaces received respectively
      the twigs from the anterior branch of the obturator nerve and the filament(s)
      from the posterior branch. The filament(s) was either indirectly derived from the
      medial stratum of the posterior branch through the formation of a common trunk
      with the twigs distributed in the obturator externus (14/23 thighs, 60.9%) or
      directly originating in the medial stratum of the posterior branch of the
      obturator nerve (9/23 thighs, 39.1%). In the close examination of the
      intramuscular distribution of the nerve to the SAB, the region innervated by the
      anterior branch of the obturator nerve could clearly be distinguished from that
      innervated by the posterior branch. The obturator nerve received fibers from
      L1234 (2/23 thighs) or from L234 (21/23 thighs), and the posterior branch of the
      obturator nerve ran through the obturator externus (18/23 thighs, 78.3%) or ran
      over the obturator externus (5/23 thighs, 21.7%), and finally emerged into the
      thigh. In view of the mode of origin of the filament(s), the structural element
      of the filament(s), and the pattern of entry of the filament(s) into the SAB, the
      fasciculus of the SAB, which is innervated by the posterior branch of the
      obturator nerve, was considered to originate in the obturator externus. Thus, the
      true nature of the SAB was concluded to be a complex product which was formed by
      a mechanism in which the fasciculus, which had separated from the obturator
      externus during the process of ontogeny, fused secondarily to the posterior
      surface of the regular adductor brevis. From findings in our series of studies,
      it was estimated that the maximum frequency of occurrence of the SAB could be
      56%. Furthermore, from a statistical point of view, the segmental composition or
      course of the obturator nerve is not considered to be related to either the
      formation or the incidence of this muscle.

PMID- 7808726
TI  - Nuclear export of recombinant baculovirus nucleocapsids through small pore or
      nuclear-pore-like structure in Sf9 cells.
AB  - Translocation of baculovirus nucleocapsids (45 nm in diameter, approximate length
      of 280-300 nm) from nucleoplasm to cytoplasm was studied morphologically using
      cryofixation and gold labeled wheat germ agglutinin (WGA-gold) during recombinant
      Autographa californica nuclear polyhedrosis virus infection in Sf9 cells.
      Nucleocapsids formed in the nucleoplasm migrated into protrusions of the nuclear
      envelope, but not into nuclear pore complexes. We found cross-like membranous
      structures. Small pores seemed to be in the protruding nuclear double membranes.
      The middle piece of a nucleocapsid was located within the small pore whereas the
      upper part was in the cytoplasm. Other nucleocapsids were situated within pores
      without colocalization of WGA-gold in the nuclear envelope. These results suggest
      that baculovirus nucleocapsids use small pores in the nuclear-derived membranes
      or incomplete nuclear pores in the nuclear envelope to migrate from the
      nucleoplasm to the cytoplasm, but not complete nuclear pore complexes proper.

PMID- 7808728
TI  - Anticomplement activity in human aqueous humor.
AB  - Twenty-six samples of human aqueous humor from patients with cataract and
      glaucoma were analyzed on anticomplement activity. The mean inhibitory rate was
      15.32 +/- 14.60%, ranging from 0.93 to 60.02%. The inhibitory effect appeared in
      a dose-dependent manner. No significant differences were found between males and
      females (p > 0.05) and between samples of different age (p > 0.05). We revealed
      that aqueous humor had an inhibitory effect on complement activity. This
      indicates that human aqueous humor has an immune regulatory function.

PMID- 7808727
TI  - Topographical anatomy of the internal mammary lymphatics in the superior
      mediastinum and anterior mediastinal lymph nodes.
AB  - The lymphatics lying along the internal thoracic artery and vein, which are
      termed the "internal mammary lymphatics" (IML), were minutely dissected in 134
      adult cadavers (80 males and 54 females, aged 27-94 years) in order to clarify
      the configuration of IML in the superior mediastinum. On the right side, IML
      frequently terminated at the brachiocephalic angle (BA) nodes and often at the
      nodes situated at an intermediate position between the internal thoracic artery
      and vein. By way of these nodes, IML communicated with regional lymphatics of the
      lung and esophagus. Moreover, IML joined the right superficial bronchomediastinal
      trunks. On the left side, IML consistently terminated at a superficial group of
      aortic arch nodes, termed the "superior phrenic nodes", lying along the left
      phrenic nerve and lying medially to the internal thoracic vein and inferiorly to
      the left brachiocephalic vein. At and around these nodes, IML joined drainage
      routes from the so-called Botallo's nodes, which received the left lung
      lymphatics. The efferents of the superior phrenic nodes formed the left superior
      bronchomediastinal trunks, and passed deeply to the left brachiocephalic vein and
      on the subclavian artery toward the left venous angle region. Consequently, IML
      formed common drainage routes with the drainage routes from the lung and
      esophagus in the superior mediastinum. A transverse communicating route of IMLs
      via the retromanubrial nodes, lying inferior to or along the left brachiocephalic
      vein, was often observed. On the right side, the communicating route terminated
      at the BA nodes or the nodes situated at an intermediate position between the
      internal thoracic artery and vein. On the left side, the route consistently
      terminated at the superior phrenic nodes. In addition to the communicating route
      described above, we identified (1) a direct and superficial transverse
      communicating route, and (2) a deep transverse communicating route. The former
      route was composed of fasciculated large collecting vessels directly connecting
      the BA nodes to the left venous angle region, lying superficial to the left
      brachiocephalic vein. The latter route was composed of several large collecting
      vessels, crossing the brachiocephalic and left common carotid arteries
      superficially, and merging into the left phrenic nodes directly or occasionally
      via the pretracheal nodes. These results suggested that IMLs of both sides can
      closely communicate with each other in the superior mediastinum.

PMID- 7808729
TI  - Previous ocular compression increases intraocular penetration of systemic drugs.
AB  - Intraocular drug penetration is dependent upon the physical and chemical
      characteristics of the drug, the manner of drug administration and the drug's
      ability to pass through the blood/aqueous barrier. Most systemically administered
      drugs do not achieve intraocular therapeutic levels. The authors present a new
      method to increase the intraocular concentration of intravenously administered
      drugs based on the premise that ocular hypotony by ocular compression produces a
      temporary break in the blood/aqueous barrier during the period of hypersecretion
      that follows to regain normal intraocular pressure levels. Vancomycin introduced
      parenterally was used as the drug model. The right eye of 22 rabbits served as
      experimental eye, while the left eye served as control. The concentrations of
      vancomycin in the aqueous humor half an hour after intravenous injection of 40
      mg/kg vancomycin in 50 ml of lactated Ringer's solution were as follows: 30.17 +/
      20.68 micrograms/ml in the right (hypotonized) eyes and 4.92 +/- 3.33
      micrograms/ml in the left (control) eyes. The difference in drug levels between
      the two sets of eyes had a high statistical significance at p = 0.001.

PMID- 7808731
TI  - Gourami lenses convert tryptophan into 3-hydroxykynurenine.
AB  - Although free tryptophan was found in the lens of both the kissing gourami
      (Helostoma temmincki) and the 3-spot gourami (Trichogaster trichopterus), only
      the lens of the latter species contained 3-hydroxykynurenine. Radiolabel
      experiments carried out on 3-spot gourami lenses in culture demonstrated that, as
      in humans, lenticular tryptophan is converted to 3-hydroxykynurenine probably via
      the intermediate kynurenine.

PMID- 7808730
TI  - Localization of M3 muscarinic receptor subtype and mRNA in the human eye.
AB  - Cholinergic agents used to lower intraocular pressure in the medical management
      of glaucoma act on muscarinic receptors in the eye. Recently, subtypes of
      muscarinic receptors have been recognized in many tissues including the eye. To
      localize the M3 muscarinic receptor subtype and m3 messenger RNA (mRNA) in the
      human eye, we used in vitro ligand binding and in situ hybridization techniques
      on post-mortem sections. We used an M3 antagonist, [3H]-4-DAMP ([3H]-4
      diphenylacetoxy-N-methylpiperidine methiodide) to identify M3-binding sites and a
      [35S]-labelled oligonucleotide probe to detect and localize m3 mRNA. M3 and m3
      mRNA were both localized in the ciliary muscle, ciliary epithelium, iris, corneal
      epithelium and anterior lens epithelium. The m3 transcript was also detected in
      the trabecular meshwork and corneal endothelium.

PMID- 7808732
TI  - Comparison of peroxidases in the retina, choroid and red blood cells.
AB  - Most of the peroxidase activity in the bovine retina is specific to glutathione
      (GSH) while the choroid contains both GSH peroxidases and ascorbate peroxidase.
      The GSH peroxidase was clearly separated from ascorbate peroxidase on a cation
      exchange column. The nonspecific peroxidase activity of hemoproteins accounts for
      the peroxidase activity detected by ascorbate oxidation. All choroidal
      hemoproteins contain subunits very similar to those of hemoglobin. The absence of
      ascorbate peroxidase in the retina indicates that the protective effect of
      ascorbate against photic injury is not due to its reaction with retinal
      peroxidase. Therefore removal of H2O2 by ascorbate peroxidase activity in the
      choroid could be a significant factor in studies where serum ascorbate
      concentrations are artificially raised far above the normal level concurrent to a
      very small rise in retinal ascorbate concentration.

PMID- 7808733
TI  - Role of naproxen as anti-oxidant in selenite cataract.
AB  - Naproxen, a nonsteroidal anti-inflammatory drug has been evaluated for its
      anticataract action in the prevention of cataracts induced by selenite.
      Administration of a single dose of sodium selenite intraperitoneally resulted in
      the development of advanced cataracts in 100% of the eyes within 5-6 days.
      Treatment with naproxen resulted in showing a significant preventive effect. The
      biochemical parameters like glutathione, malonaldehyde or soluble and insoluble
      protein contents indicate that selenite causes cataract due to oxidative stress.
      The observations also suggest that naproxen acts as an anti-oxidant.

PMID- 7808734
TI  - Autoradiographic distribution of the eye monoaminergic synaptic vesicles.
AB  - The ligand [3H]dihydrotetrabenazine ([3H]TBZOH), a tritiated derivative of the
      monoamine depleting agent tetrabenazine, has been reported to bind specifically
      to the transporter present on the membrane of monoaminergic synaptic vesicles. We
      have studied the pharmacological characteristics of [3H]TBZOH binding to rabbit
      eye sections and the anatomical distribution of [3H]TBZOH binding sites in
      rabbit, rat and human eyes by in vitro autoradiography. In rabbit eye sections,
      [3H]TBZOH binding bound to a single class of binding sites (Kd = 4.1 nM, Bmax =
      30.6 fmol/mg protein). When animals were kept for various times after death
      before removal of the eyes, the mean density of [3H]TBZOH binding sites decreased
      to 94 and 93% of control values after 24 and 48 h, respectively. In both species,
      the topographical distribution of [3H]TBZOH sites shows a pattern of distribution
      similar to that of monoaminergic innervation of the eye. The present data
      demonstrate that [3H]TBZOH can be used for the identification and the
      quantitation of monoamine-containing neurons in the mammalian eye.

PMID- 7808735
TI  - Snellen visual acuity versus pattern reversal visual-evoked response acuity in
      clinical applications.
AB  - We compared the best-corrected Snellen acuity (SA) and the pattern reversal
      visual-evoked response (PVER) acuity in normal subjects and patients. Forty-two
      eyes of 42 normal subjects were controls; 457 eyes of 329 patients comprised the
      patient group. A steady-state stimulus with five check sizes ranging from 160 to
      10 min in 1.0-octave steps was used. The PVER acuity was derived from the best
      fit linear function relating the amplitude to the log-adjusted check size. Three
      intercepts of 0, 1 and 2 microV were used in both groups, and the PVER acuities
      were called P0, P1 and P2. The SAs in normal subjects ranged from 20/15 to 20/20
      (mean, 20/18.3) and in patients from 20/15 to 20/1,600 (mean, 20/56.9). In
      normals, the P0 showed the best agreement with the SA (mean acuity difference,
      +0.34 octave). The SA and P0 agreed within +/- 2.0 octaves in 33/42 (78.6%) eyes.
      In patients, the P0 also showed the best agreement with the SA; 306/457 (67.0%)
      eyes showed an acuity difference within +/- 2.0 octaves. Unlike normals, 83/457
      (18.2%) eyes showed an acuity difference > -3.0 octaves. These eyes mostly had
      optic nerve disease with a flattened PVER amplitude-check size function curve.
      The P0 seems to correlate better with SA than P1 and P2, but this analytical
      method may be less effective in the presence of certain pathologic conditions.

PMID- 7808736
TI  - Necrotizing retinitis in severe combined immunodeficiency mice following
      intracameral inoculation of herpes simplex virus type 1.
AB  - Necrotizing retinitis in severe combined immunodeficiency (SCID) mice following
      intracameral inoculation of herpes simplex virus type 1 provided an experimental
      model for acute retinal necrosis in AIDS and other immunocompromised patients. In
      order to assess the involvement of the immunological response in the
      pathogenesis, adoptive transfer experiments were conducted. Without transfer,
      SCID mice developed predominantly unilateral necrotizing retinitis and died
      within 10 days. Transfer of immune serum lengthened the survival time but
      resulted in bilateral necrotizing retinitis. Two of 5 mice transferred with CD4+
      T cells and none of 7 transferred with CD8+ T cells developed bilateral
      necrotizing retinitis. Our results indicate that ipsilateral retinal necrosis
      occurs with or without a specific immunological response, and that antibodies
      and/or CD4+ T cells accelerate the contralateral retinal necrosis.

PMID- 7808737
TI  - [Degenerative chondroarthropathy of the sternocostal joint following heart
      surgery].
AB  - Involvement of the sternocostal joints was investigated in a series of 46 males
      and 18 females following median sternotomy annually in a 5-year period and
      compared to 62 age- and sex matched control subjects after one year solely. Both
      groups had a mean age of 49.2 years. The degenerative chondroarthropathy of
      sternocostal joints was 1.69-times more frequent in heart operated upon patients
      as compared to control persons. Based on radiographic findings the degenerative
      chondroarthropathies were classed in 0 to 3 severity groups. Were seen articular
      space narrowing in 95.4%, osteophytes of the margin of the articular surface in
      88%, subchondral bony eburnation in 79% and cystic radiolucencies in 48.9% of
      sternocostal joints on poststernotomy standard plain film tomograms. Not occurred
      intraarticular gas phenomenon and bony ankylosis. The development of
      arthropathies is traced back to mechanical stress-related predisposing factors
      and stressed the importance of oculoneutral dehiscences that simulated normal
      roentgenanatomic projections and caused a masked insufficiency in sternocostal
      junctions.

PMID- 7808738
TI  - [Hypocholesterolemia and other lipoprotein disorders in myelofibrosis].
AB  - In the recent years more and more data suggest a significant relationship between
      malignant diseases and cholesterol, respectively lipoprotein metabolism. It is a
      significant decrease of cholesterol in primary myelofibrosis (agnogenic myeloid
      metaplasia) and in secondary myelofibrosis. Similarly, the HDL and LDL
      cholesterol levels are also decreased in these diseases. On the contrary, the
      triglyceride level is significantly higher in these groups, 41 patients with
      agnogenic myeloid metaplasia and 16 patients with myelofibrosis following
      polycythaemia vera were examined. Decrease of serum cholesterol level was
      significant: 3.7 and 3.3 mmol/l and 5.2 mmol/l in 76 healthy controls, as the
      mean values.

PMID- 7808739
TI  - [Vitamin D3 and its analogues: a new age in the treatment of psoriasis
      vulgaris?].
AB  - The introduction of this article is devoted to the physiological role of vitamin
      D3 and its synthesis. The authors refer to the accidental introduction of vitamin
      D3 into the psoriasis treatment, which later led to the development of a less
      toxic vitamin D3 analog named calcipotriol, and its administration as a topical
      antipsoriatic agent. Reviewing the literature the authors discuss the
      pharmacological and immunological effects of calcipotriol as well as the
      potential applications of vitamin D3.

PMID- 7808740
TI  - [Rare late complication of transcystic drainage].
AB  - The authors performed 3539 successful endoscopic retrograde cholangio
      panreatographies between 1982 and 1992. In 1160 (32.7%) of the cases was revealed
      some kind of pathological condition. In connection with one case, following
      conventional cholecystectomy, a very rare complication was diagnosed by
      endoscopic means. There was a stent-like object, hanging into the duodenal lumen,
      through a parapapillar fistula. This was surgically removed. It turned
      retrospectively out that the removal of K-32 feeding tube used as a transcystic
      drain 18 years earlier had managed only partially. After this period of time did
      it cause a biliary flow obstruction and a choledocho-duodenal fistula. The
      endoscopic diagnostic possibilities, course of disease and treatment is presented
      hereby.

PMID- 7808741
TI  - [The life and work of Lajos Aranyi (1812-18870].

PMID- 7808742
TI  - [Evolution of history of medicine and its acceptance].

PMID- 7808743
TI  - [Possibility of conservative management of childhood vesiculo-ureteral reflux].

PMID- 7808744
TI  - [Problems of prevention of congenital adrenal hyperplasia].

PMID- 7808745
TI  - [Development of reconstruction surgery of pharynx and esophagus].
AB  - We present historical review of pharyngooesophageal reconstruction after
      resection for carcinoma and pharynx and oesophagus stenosis. This paper presents
      development and complications after surgical treatment of pharynx and oesophagus.
      The most important of pharynx and oesophagus resection is reconstructive surgery.

PMID- 7808746
TI  - [Laryngeal cancer: postop complications and possibilities of their correction].
AB  - The aim of the paper is to present the surgical methods applied in a 76 year old
      patient treated for carcinoma of the larynx. As an effect of the carried out
      total laryngectomy, extensive pharyngeal fistula occurred. The fistula was closed
      with myocutaneous flap which was pedunculated on double reversed pectoral major
      muscle. Due to lymphatic metastases surgical dissection of lymphatic system of
      the left side of the neck was performed 2 years after laryngectomy. During this
      operation the left common cervical artery was removed (Goretex graft). Next
      cobaltotherapy was applied. After following 2 years the skin necrosis just over
      the flap occurred. It was caused by shirt collar pressure. Because of the major
      bleeding common cervical artery was oligated. During this procedure the frontal
      wall of the oesophagus was damaged and again pharyngeal fistula appeared.
      Attempts at closing it with flaps pedunculated on pectoral major muscle and
      trapezius muscle did not succeed. Finally fistula was closed with cylindric flap
      from the abdomen connected with the cutaneous flap from surrounding fistula
      tissues. Following recognition of this illness the patient had undergo nine
      consecutive, extensive operations. Ten years after diagnosis he is still alive
      and leads a life appropriate to his age.

PMID- 7808747
TI  - [Surgical treatment of nasal bleeding in patients admitted to the 2nd ENT
      department in Zabrze in the years 1981-1990].
AB  - The authors presented 11 cases of excessive and recurrent nose bleeding treated
      surgically in 2nd ENT Department. The vascular ligation of the internal maxillary
      artery or ethmoidal arteries was carried out. In the 3 years period of follow up
      no bleeding hasn't been reported.

PMID- 7808748
TI  - [Loratadine in the treatment of seasonal allergic rhinitis].
AB  - A single blind, placebo-controlled, parallel-group study was performed during a
      pollen season in 41 patients suffering from seasonal allergic rhinitis. A group
      of 26 patients was treated with loratadine (10 mg daily in one dose) for 3 weeks.
      Placebo was given in the group of 15 patients (1 tablet daily) during 8-10 days.
      The following parameters were assessed: clinical symptoms (rhinorhea, sneezing,
      blockage, nasal itching, eye symptoms), rhinoscopy, at baseline and after 8 and
      21 days of the treatment. Eosinophils in nasal secretion were countered before
      and after the medication. Patients recorded daily nasal and ocular symptoms and
      possible adverse events in diary cards. It was shown a statistical significant
      improvement of clinical symptoms in the group treated with loratadine in
      comparison with the placebo group (p < 0.01). Very good and good results were
      observed in 84.6% of the treated with loratadine patients. The reduction of
      eosinophilia in nasal secretion during medication period was noted. Loratadine
      did not induce more side effects than placebo.

PMID- 7808749
TI  - [Treatment of upper respiratory tract infections with broncho-vaxom++: a
      therapeutic alternative to chemotherapy?].
AB  - Studies were performed on 21 industry-products sellers suffering to recurrent
      infections of upper respiratory tract. Immunostimulating treatment was performed
      using Broncho-vaxom administered during 6 months. Drug was applied by 10
      consecutive days every month, 1 tablet at the morning on empty stomach (before
      breakfast). During immunotherapy the decrease in work-absences and diminution of
      some pathological symptoms were noted. No additional chemotherapeutics were taken
      during Broncho-vaxom. Although the efficacy of immunostimulatory therapy with
      Broncho-vaxom is not certainly proved, treatment with this drug seems to present
      be an alternative for chemotherapeutics in recurrent infections of upper
      respiratory tract. That treatment is probably like the psychotherapy.

PMID- 7808750
TI  - Tympanoplasty in children--our experience in Riyadh, Saudi Arabia.
AB  - A seven years results of 75 cases of tympanoplasty without mastoidectomies in
      children is presented and analyzed. The study showed a perforation closure rate
      of 81.33%, hearing improvement to within 25 dB was 61.33%. The hearing did not
      improve in 18.66%. There is no higher incidence of recurrent perforation in
      children as compared to adults. In developing country such as Saudi Arabia
      experiences, skill, and proper development of facilities for management and post
      operative care in distant areas may prove helpful in improving the results of
      tympanoplasty.

PMID- 7808751
TI  - [Computer system of electronystagmographic examination. Part I. Measuring
      equipment and algorithm of ENG test].
AB  - The work presents the computer system created by the author for automatic
      registration and analysing oculomotor response records evoked by the stimulation
      of the vestibular organ. The basis elements of the system had been described. It
      consists of microcomputer IBM PC/XT/AT, measurement and stimulatory apparatus,
      multimodular controlling and analytical software as well as the algorithm of
      system management.

PMID- 7808752
TI  - [The first experience in diagnosis and rehabiliation in patients with cochlear
      implant "Nuclear Mini System 22"].
AB  - The first qualification for cochlear implant "Nucleus" was performed on the basis
      of audiological tests. Next stage was conversation with a patient and his family
      about motivation of longterm rehabilitation. Then the two very important
      investigations were carried out--the computer tomography which showed inner ear
      structure, and electric promotory test. In rehabilitation process original
      "Nucleus" partially modified and Polish linguistic articulation lists were used.

PMID- 7808753
TI  - [Difficulties and complications during surgical treatment of otosclerosis].

PMID- 7808754
TI  - Fourier analysis in the objectivisation of auditory brain stem responses in
      newborns.
AB  - Fourier analysis (FFT) of auditory brain stem responses induced by stimuli of 90,
      70 and 40 dB HL was carried out in group of 45 full-term and pre-term neonates.
      It was stated that with postnatal newborn's development complex IV/V was observed
      more frequently for the more immature newborn. It influences also the power
      strength spectrum obtained. In responses with IV/V complex the frequency range is
      considerable and significantly reduced by about 100-200 Hz. It was observed that
      general state of newborn at the birth influences the frequency range as well as
      from the shape of score reproducibility and reliability of spectrum is
      significantly better. It was noticed also that the shape and form of spectrum in
      about threshold and threshold responses is significantly similar irrespective of
      the intensity of threshold stimulus. The shape and form of responses spectra for
      stimuli of 30-40 dB HL (in a group of children with normal hearing) and of 80-90
      dB HL (in a group of children with severe hearing impairment) are identical. The
      above findings allow us to show the importance of Fourier analysis for
      objectivisation of subjective evaluation of auditory brain stem responses.

PMID- 7808755
TI  - [Hearing status, causes of impairment and rehabilitation of the hard-of-hearing
      students in the elementary school].
AB  - The entering to the hard-of-hearing elementary school require some stage of
      speech development. This situation demands the early diagnosis of hearing
      disorders, early hearing aids and two or more years of speech and hearing
      rehabilitation. In the group of hard-of-hearing school pupils the detailed
      history was taken. The aim of this analysis was to clarify the condition
      necessary to enter to the hard-of-hearing elementary school. We have asked about
      the age of diagnosis, kind of hearing impairment, time and intensity of
      rehabilitation, hearing aids utility and speech development status.

PMID- 7808756
TI  - [The topodiagnostic value of direction of cervical nystagmus in vertebro-basilar
      insufficiency].
AB  - The estimation of the topodiagnostic value of cervical nystagmus and its changes
      in vertebrobasilar insufficiency was the aim of this work. The analysis was
      performed on 79 patients with the positive cervical nystagmus test. There was not
      any correlation between the side of neurologic signs, the level of CNS damage and
      the direction of cervical nystagmus. The changes of nystagmus direction are
      usefulness topodiagnostically too.

PMID- 7808757
TI  - [Experimental perilymphatic fistula].
AB  - The round window membrane of the inner ear of 15 guinea pigs was removed under
      ketamine anaesthesia. Perilymph was aspirated through the round window in 8
      guinea pigs. The round window membrane had regenerated spontaneously after 2
      weeks. Light microscopy revealed hair cell loss localized to the apical and basal
      turns of the cochlea. Morphological examinations showed the most severe changes
      in these group of aspirated animals. Abrupt pressure imbalance may be a causative
      factor of sensorineural hearing loss.

PMID- 7808758
TI  - [Drug addiction complicating treatment of chronic otitis media].
AB  - The case of drug addiction which has made the diagnosis and treatment of chronic
      otitis media difficult was presented. The clinical course and treatment
      complicated by withdrawal symptoms were also discussed.

PMID- 7808759
TI  - [Inflammatory foci in palatine tonsils and paranasal sinuses in children with
      insulin-dependent diabetes mellitus].

PMID- 7808761
TI  - Antigenic diversity of the asexual developmental stages of Eimeria tenella.
AB  - Total polypeptides from unsporulated and sporulated oocysts, sporozoites and the
      first two generations of merozoites of Eimeria tenella were fractionated by
      electrophoresis through polyacrylamide gels. The parasites are complex and the
      arrays of polypeptides differ for each of the developmental stages indicating
      that there is stage-specific control of gene expression. In particular, first
      generation merozoites display a markedly different polypeptide profile to that of
      either sporozoites or second generation merozoites. Changes in antigenicity
      during sporulation and the antigenic relationships between the three asexual
      zoite stages were examined by probing electroblotted polypeptides with a panel of
      antisera raised in rabbits to purified preparations of each stage. Antigenic
      cross-reactivity is well maintained throughout sporulation even though the sizes
      of antibody-reactive polypeptides change. In contrast there is a marked lack of
      cross-reactive epitopes between sporozoites, first and second generation
      merozoites.

PMID- 7808760
TI  - Vaccination of goats against the trematode Schistosoma bovis with a recombinant
      homologous schistosome-derived glutathione S-transferase.
AB  - We assayed the vaccine potentialities of a recombinant S. bovis-derived
      glutathione S-transferase (rSb28GST), member of a molecular family already shown
      to have protective capacities in the S. mansoni and S. japonicum models.
      Injection of the rSb28GST in Freund's Complete Adjuvant resulted in good specific
      IgG responses allowing all the animals to display high antibody titres on the day
      of experimental challenge with S. bovis cercariae. No statistically significant
      differences were observed in the faecal egg output. Although tissue egg counts in
      vaccinated animals were lower than in controls, the difference was not
      statistically significant, apart from the number of eggs trapped in the liver (P
      < 0.05). Likewise, PCV values remained parallel between the two groups. However,
      immunized goats gained 1.4 kg of body weight throughout the experiment whereas
      controls lost 1.2 kg (P < 0.05). In addition, the mean worm burden, assessed by
      perfusion 20 weeks after infection, was significantly reduced by 48% in the
      vaccinated group, the sex ratio being unaffected. It appears that a recombinant
      homologous protein can affect, in a natural host, the course of an experimental
      infection with a local strain of S. bovis, by affecting worm viability but not
      fecundity. These results also point to the striking differences in the effect of
      vaccination according to animal species. Because it has the capacity to prevent
      growth impairment due to schistosome pathogenicity, the molecule can be proposed
      as a valuable tool in the development of vaccine-based control programs in
      endemic areas.

PMID- 7808762
TI  - A theoretical framework for the immunoepidemiology of blocking antibodies to
      helminth infection.
AB  - Epidemiological evidence is widely cited in support of the hypothesis that
      certain antibody responses to human helminth, especially schistosome, infection
      exhibit blocking activity. This evidence includes positive correlations between
      antibody levels and the rate of re-establishment of infection following
      chemotherapy, antibody levels which peak in younger and more susceptible age
      classes, lower ratios of blocking antibodies to others in older and less
      susceptible age classes. In this paper simple mathematical models are used to
      explore expected age-specific relationships between antibody levels, parasite
      burdens and re-establishment rates for different combinations of protective,
      neutral and blocking immune responses. In general, all the above cited patterns
      may be generated without invoking blocking activity, especially if the abilities
      to produce different antibody responses have different immunological memories,
      i.e. persist for different lengths of time in the absence of continued exposure
      to antigen. None of these patterns, including a positive correlation between
      antibody levels and rates of re-establishment following chemotherapy, offers
      unambiguous evidence for blocking activity. Blocking activity is also predicted
      to affect the shape of the age-intensity curve and the relationship between
      susceptibility to infection and age in ways which are not necessarily consistent
      with the epidemiological evidence. The importance of the blocking activity, which
      has been convincingly demonstrated in vitro, to population level
      immunoepidemiological patterns in the field therefore remains uncertain.

PMID- 7808763
TI  - Resistance and disease in Brugia malayi infection of ferrets following prior
      infection, injection of attenuated infective larvae and injections of larval
      extracts.
AB  - A partial resistance expressed by a 53% to 78% reduction in lymphatic filariae
      from a challenge infection was induced in ferrets (Mustela putorius furo) by a
      prior infection and by injection of radiation attenuated infective larvae (L3)
      but not by injections of lyophilized microfilariae (mf) or L3. Equivalent
      acquired resistance was demonstrated with and without overt filarial disease. A
      prior infection resulted in peripheral lymphoedema in approximately one-third of
      the amicrofilaraemic resistant ferrets following challenge infection and
      injection of attenuated larvae resulted in inflammatory responses characteristic
      of a hyper-responsive syndrome in one-half of the amicrofilaraemic ferrets.
      Injections of lyophilized mf inhibited microfilaraemia and promoted development
      of lymphostatic disease. A limited examination of immune responses and
      histopathology suggested that disease in partially resistant ferrets was
      associated with high TH2 dependent responses directed, at least in part, to
      mature filariae and to mf. Mechanisms of resistance were not identified.

PMID- 7808764
TI  - Cytokine profile of protective anti-Trichinella spiralis CD4+ OX22- and non
      protective CD4+ OX22+ thoracic duct cells in rats: secretion of IL-4 alone does
      not determine protective capacity.
AB  - We analysed the cytokine profile of a T cell subset (CD4+ CD45 RC-) that confers
      protection against Trichinella spiralis infection in rats. These CD4+ cells are
      generated in the gut and appear in the thoracic duct lymph within 72 h after
      infection. Cytokine mRNA levels for IL-2, IL-3, IL-4, IL-5, IL-10 and IFN-gamma
      and functional cytokine secretion for IL-4, IL-5, IFN-gamma, TNF-alpha and mast
      cell differentiation activity were tested in vitro following stimulation with T.
      spiralis antigens. Compared to a non-protective T cell population (CD4+ CD45 RC+
      or CD8+), also isolated from the same thoracic lymph, no significant differences
      were observed in the levels of mRNA for IL-2, IL-3, IL-4, IL-5, IL-10 or IFN
      gamma in the protective CD4+ CD45 RC- cells. However, analysis of the cytokine
      activities in culture supernatant of these T cell subsets following 24 h
      stimulation in vitro with T. spiralis antigens showed that significant IL-4 and
      IL-5 activity but little IFN-gamma or TNF-alpha was secreted by the protective
      CD4+ CD45- RC- cells. Whereas the non-protective CD4+ CD45 RC+ cells secreted
      significant levels of IL-4, IFN-gamma, mast cell differentiating activity and TNF
      alpha but little IL-5 activity. Non-protective CD8+ cells were found to secrete
      IL-4 but not IL-5. Production of IL-4 was essentially equal for both protective
      and non-protective T cell subsets. These findings suggest that the presence or
      absence of IFN-gamma secretion, rather than IL-4 alone, determines whether a T
      cell subset has protective activity against T. spiralis infection in rats.

PMID- 7808765
TI  - Complex formation of human alpha-1-antitrypsin with components in Schistosoma
      mansoni cercariae.
AB  - Human alpha-1-antitrypsin (alpha 1-AT) was incubated with an extract of
      Schistosoma mansoni cercariae or porcine pancreatic elastase and analysed by
      immunoelectrophoresis and Western blotting. The inhibitor was shown to form
      complexes with components in S. mansoni cercariae in the same way as elastase.
      The role of alpha 1-AT in S. mansoni infection is discussed.

PMID- 7808766
TI  - Chemotaxis of human monocytes by synthetic peptides that mimic segments of
      Porphyromonas gingivalis fimbrial protein.
AB  - Porphyromonas gingivalis strain 381 fimbriae and their synthetic peptide segments
      were assessed for migration-stimulating activity on human peripheral blood
      monocytes by multiwell chemotaxis assay. P. gingivalis 381 fimbrial protein was
      found to markedly enhance migration of human monocytes. The observed increase in
      monocyte migration occurred mainly directed toward a positive stimulus
      (chemotaxis). Furthermore, lipopolysaccharides extracted from P. gingivalis 381
      were shown to induce chemotaxis and chemokinesis. It was also revealed that the
      migration of monocytes was increased by specific synthetic peptide segments,
      FP381(61-80) and FP381(171-185), that correspond to GKTLAEVKALTTELTAENQE and
      DANYLTGSLTTFNGA, respectively, based on the amino acid sequence of the fimbrial
      subunit protein proposed by Dickinson et al., and the migration stimulation was
      ascribed to chemotaxis. Furthermore, within the amino acid sequences, the
      LTXXLTXXN sequence may play an important role in binding the organisms to
      monocytes and macrophages and in the induction of migration-stimulating activity.

PMID- 7808767
TI  - Neutrophil function in juvenile periodontitis: induction of adherence.
AB  - Polymorphonuclear leukocytes (neutrophils) in patients with localized juvenile
      periodontitis with decreased chemotaxis exhibit increased adherence. The
      molecular basis of increased adherence of neutrophils in localized juvenile
      periodontitis is not clear. We show that the neutrophils from localized juvenile
      periodontitis patients with decreased neutrophil chemotaxis and increased
      adherence exhibit increased expression of the CD11/CD18 family of adherence
      molecules, Mac-1, leukocyte function-associated antigen (LFA-1) and p150,95, as
      compared with neutrophils obtained from systemically and periodontally healthy
      controls. Treatment of neutrophils obtained from healthy subjects with sera from
      localized juvenile periodontitis patients resulted in an increased expression of
      Mac-1, leukocyte function-associated antigen and p150,95 molecules. Sera obtained
      from health subjects, patients with adult periodontitis or localized juvenile
      periodontitis patients with normal chemotaxis did not increase the expression of
      CD11/CD18 molecules on the neutrophils obtained from healthy subjects. The
      ability of localized juvenile periodontitis sera to induce expression of
      adherence molecules was at least partially inhibited by pretreatment of localized
      juvenile periodontitis sera with anti-tumor necrosis factor and anti-interleukin
      1 antibodies. Furthermore, increasing concentrations of rh-tumor necrosis factor
      alpha and interleukin-1 beta also induced increased expression of the Mac-1
      molecule on neutrophils from localized juvenile periodontitis patients and
      healthy subjects. The increased expression of adherence molecules on neutrophils
      from localized juvenile periodontitis patients was sustained and could not be
      reversed by treatment of localized juvenile periodontitis neutrophils with sera
      obtained from healthy subjects. The upregulation of adherence molecules on
      neutrophils by localized juvenile periodontitis sera in these experiments
      emphasizes the physiologic importance of quantitatively small but biologically
      significant levels of cytokines in the modulation of neutrophil functions in
      localized juvenile periodontitis.

PMID- 7808769
TI  - Immunoglobulin A antibodies to mutans streptococci in human saliva and serum
      comparing fresh and subcultivated strains and activity in repeated saliva
      samples.
AB  - The aims of this study were i) to characterize and compare the sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis protein patterns of reference
      Streptococcus mutans and Streptococcus sobrinus strains, subcultivated for years,
      with fresh isolates of the same serotype; ii) to study possible differences
      between the human salivary immunoglobulin A (IgA) activity to reference strains
      and to fresh bacterial isolates of the saliva donors; iii) to examine for
      potential differences in the salivary IgA activity to the streptococcal antigens
      during 1 week; and iv) to map, in the same individuals, the serum IgA activity
      against the selected bacteria. S. mutans reference and fresh isolated strains
      showed a similar protein pattern with few exceptions. The immunoblot also
      revealed similarity in saliva IgA response, with only one subject's saliva
      displaying clearly one band's difference. For S. sobrinus a larger discrepancy
      was seen. The antibody activity during the one week interval was essentially
      unchanged. When incubated with serum, a different immunoblot profile was seen
      compared with saliva, although most bands revealed by saliva were also displayed
      by serum.

PMID- 7808768
TI  - Neutrophil lysosomal nonoxidative microbicidal proteins in early-onset
      periodontitis.
AB  - The purpose of this study was to evaluate whether the reduced microbicidal
      activity of polymorphonuclear leukocytes (neutrophils) in patients with early
      onset periodontitis is associated with a deficiency of nonoxidative microbicidal
      proteins. Neutrophils from 10 patients with early-onset periodontitis and 8
      healthy control subjects were assessed for elastase isozymes 1 through 4,
      cathepsin G isozymes 1 through 4 and defensins (HNP-1, HNP-2 and HNP-3) using
      cationic and acid urea polyacrylamide gel electrophoresis. The results showed
      that both the total content and the relative distribution of elastase and
      cathepsin G isozymes was normal in neutrophils of patients with early-onset
      periodontitis. However, the HNP-3 content was significantly reduced in
      neutrophils from patients with generalized early-onset periodontitis. These
      findings indicate that the impaired microbicidal activities of neutrophils in
      patients with early-onset periodontitis does not appear to be based on an
      elastase or cathepsin G abnormality in neutrophils. Due to the high variability
      of HNP-1 + 2 and HNP-3 in neutrophils of control subjects, the reduced HNP-3
      content in neutrophils probably plays a minor role in the pathogenesis of
      generalized early-onset periodontitis.

PMID- 7808770
TI  - Adoptive transfer of cloned T helper cells ameliorates periodontal disease in
      nude rats.
AB  - We have previously described a T helper cell 2-type clone, A3, of rat T cells
      that provides help for antibody production to Actinobacillus
      actinomycetemcomitans in vitro and in vivo in normal (euthymic) isogeneic Rowett
      strain recipient rats. Adoptive transfer of this T helper cell clone to euthymic
      rats also protects them from periodontal bone loss induced by oral infection with
      A. actinomycetemcomitans. In the present study, to assess the cell requirement
      for protection, A3 clone T lymphocytes (10(6)) or naive lymph node (6 x 10(4)) T
      cells, or A3 plus naive lymph node T cells (6 x 10(4)) were adoptively
      transferred to groups (n = 7-9) of 30-day-old Rowett athymic nude (rnu/rnu) rats.
      All recipients were also immunized (intraperitoneally) with 10(7) killed A.
      actinomycetemcomitans on the day of T cell transfer and orally infected with
      these bacteria on each of the next 5 days. Recipients of the combined A3+lymph
      node T cell transfer showed significantly increased serum immunoglobulin G (IgG)
      and IgM antibody to A. actinomycetemcomitans and in vitro proliferation of spleen
      lymphocytes to A. actinomycetemcomitans as antigen compared with nude animals
      receiving lymph node T cells only. Although other possibilities are discussed, we
      inferred that these differences might be due to successful population of the
      congenitally athymic rats by A3 clone cells given with a small number of normal
      autologous naive lymph node T cells. The result of this co-transfer of naive T
      cells with the A3 clone cells seemed to be greatly increased antibody production
      and protection from periodontal bone loss.

PMID- 7808771
TI  - Transposon Tn5 mutagenesis of Actinobacillus actinomycetemcomitans via
      conjugation.

PMID- 7808772
TI  - Utilization of glutathione (L-gamma-glutamyl-L-cysteinylglycine) by Fusobacterium
      nucleatum subspecies nucleatum.
AB  - Although fusobacteria use amino acids and peptides as energy source, it is not
      known whether they are able to actively transport peptides into the cell. In the
      present study the tripeptide glutathione was used as a model substance to
      investigate peptide uptake in Fusobacterium nucleatum subsp. nucleatum. Cells
      harvested after 2 days of growth on blood agar or in their exponential growth
      phase in broth were suspended in buffer with glutathione, L-cysteinylglycine and
      L-cysteine. As a measure of cell uptake, the formation of hydrogen sulfide was
      followed. Cells from blood agar had a low capacity to form hydrogen sulfide from
      the tripeptide glutathione and the dipeptide L-cysteinylglycine. However,
      hydrogen sulfide was formed from L-cysteinylglycine, but not from glutathione or
      from L-cysteine, by cells grown in broth in such a way that it strongly indicated
      an active transport of L-cysteinylglycine with a Km of 18 microM. Hydrogen
      sulfide was efficiently formed from glutathione by cells grown in broth in the
      presence 1 mM glutathione. In these cells a glycylglycine-dependent L-gamma
      glutamyl peptidase activity was induced. It is probable that the efficient
      utilization of glutathione for hydrogen sulfide formation mirrored the uptake of
      L-cysteinylglycine after an L-gamma-glutamyl peptidase had split L-glutamate off
      from glutathione.

PMID- 7808773
TI  - Enumeration of viable oral spirochetes from periodontal pockets.
AB  - We recently developed a successful method for quantifying oral anaerobic
      spirochetes in pure culture by a viable count. New oral spirochete medium was
      used with low temperature-gelling agarose in polystyrene tissue-culture flasks.
      We have extended the use of this method to determine the viable count of
      spirochetes from periodontal pockets. Sixteen subgingival plaque samples were
      obtained by insertion of sterile paper points into deep periodontal pockets. The
      points were placed into reduced transport medium at chairside, vortexed in the
      microbiology laboratory and aliquots of the medium inoculated into molten new
      oral spirochete-agarose medium (37 degrees C) containing rifampin (20
      micrograms/ml) in a flask. Subsequent dilutions were made from this initial flask
      to other flasks containing selective medium in sequence. All flasks were
      incubated anaerobically. Most other subgingival bacteria were selectively
      inhibited by rifampin. Spirochete colonies were typically spherical and were
      either dense or cottony. Their identities were checked by darkfield examination.
      Counts of colony-forming units of cultivable spirochetes ranged from 12.5% to
      28.2% of the total cultivable anaerobic flora by the method described.

PMID- 7808774
TI  - Homology among Treponema denticola plasmids.
AB  - Three of 16 isolates of Treponema denticola were found to contain small (2.0-2.7
      kb) cryptic plasmids. These were pTD1 from T. denticola ATCC 33520, pTD2 from
      strain T32A, and pTD3 from strain D3A1. These plasmids were characterized by
      restriction mapping and cloned into E. coli plasmid pUC19. Extensive homology
      between these plasmids was revealed by Southern blot, and single-stranded DNA
      regions were found by neutral Southern blots and S1 nuclease mapping. These
      plasmids were not found in serovars usually associated with human periodontal
      disease nor are they universal in all T. denticola strains and serovars.

PMID- 7808775
TI  - Transmission of oral Prevotella melaninogenica between a mother and her young
      child.
AB  - Most likely, young children acquire their oral microflora by frequent transfer of
      bacteria between family members. The possible transmission of obligately
      anaerobic Prevotella melaninogenica recovered from 11 mother-child pairs was
      examined by ribotyping. One to 18 isolates (mean 13) per child from different
      oral sampling sites and 4 to 17 (mean 10) isolates per mother from stimulated
      salivary samples, collected on 2 occasions, were analyzed. On sampling, the mean
      ages of the children were 4 months and 32 months, respectively. Restriction
      endonucleases KpnI and ClaI were chosen for the digestion of chromosomal DNA. DNA
      fragments were electrophoretically separated, blotted onto a nylon membrane and
      hybridized with rRNA operon of Escherichia coli. DNA-DNA hybrids were detected
      immunologically. Extensive genetic heterogeneity, 101 distinct ribotypes, was
      observed among 248 P. melaninogenica isolates studied. Both mothers and children
      harbored several (up to 7) ribotypes which, apart from 3 ribotypes, were
      distinguishable in unrelated subjects. Several P. melaninogenica ribotypes were
      detected on both sampling occasions over 2 years apart. Identical ribotypes were
      found in 6 of the 11 mother-child pairs, 1 to 2 similar ribotypes per pair. This
      suggests the transmission of P. melaninogenica between the mother and her child,
      probably via maternal saliva. However, the unique ribotypes found in these
      children also indicate that other sources besides the mother influence the oral
      colonization of young children.

PMID- 7808776
TI  - Effect of chlorhexidine and toothbrushing on the presence of bacteria on gingival
      and buccal epithelial cells.
AB  - Swabs of buccal and gingival epithelial cells from healthy young adult donors
      were washed in physiological saline solution, smeared on glass slides and stained
      with acridine orange. The presence of bacteria attached onto epithelial cells was
      examined under a fluorescence microscope. Four hours after a chlorhexidine rinse,
      the number of cells with > 50 attached bacteria had almost completely vanished.
      The degree of bacterial colonization seemed to re-establish at a level exceeding
      the baseline. One week after chlorhexidine treatment the degree of colonization
      was still over the control level. Toothbrushing with a conventional toothpaste
      reduced immediately the number of cells with > 50 bacteria. The colonization had
      re-established to the pre-washing levels at the buccal sites at 1 h and at the
      gingival sites at 4 h after toothbrushing. A method for the evaluating of the
      antimicrobial power of oral hygiene products is presented.

PMID- 7808777
TI  - Absence of Helicobacter pylori in subgingival samples determined by polymerase
      chain reaction.
AB  - The polymerase chain reaction was used for the detection of Helicobacter pylori
      from subgingival plaque in 336 periodontitis patients. A pair of primers derived
      from the H. pylori urease gene A served to amplify a targeted 411-bp fragment of
      genomic DNA. This technique permitted the detection of as few as 60 H. pylori
      cells. Paper point samples from 3 deep periodontal pockets per patient were
      immersed in 1 ml of phosphate-buffered saline or distilled water, DNA was
      solubilized by detergent/protease method, 3.7 microliters or 37 microliters of
      lysate supernatant was used as template, and the amplification product was
      analyzed in 1% agarose gel containing ethidium bromide. Each experiment included
      purified DNA and cell lysate of H. pylori as positive controls. The presence of
      bacteria in the sample was verified by a primer pair common to prokaryote 16S
      rRNA. The present study did not reveal the specific polymerase chain reaction
      amplification product characteristic of H. pylori. We conclude that periodontal
      pockets do not constitute a natural reservoir for H. pylori.

PMID- 7808778
TI  - [Melatonin and the pineal gland: quid novi?].

PMID- 7808779
TI  - [Ion channels in B lymphocytes].

PMID- 7808780
TI  - [Peptides of chemical immunity in vertebrates].

PMID- 7808781
TI  - Susceptibility of multiresistant serotype 012 Pseudomonas aeruginosa to
      fosfomycin in combination with other antibiotics.
AB  - Serotype 012 represented 15% of 244 isolates of Pseudomonas aeruginosa isolated
      in the hospital over a 2 year-period and most isolates of this serotype were
      resistant to multiple antibiotics. Combination experiments showed that fosfomycin
      and amikacin together were active against 92% of 012 isolates. It is recommended
      that serotyping be used systematically to identify 012 strains rapidly and
      fosfomycin/amikacin be considered as a presumptive antipseudomonal therapy in 012
      infections.

PMID- 7808782
TI  - [Placental penetration of cefpirome (HR 810): study of fetal concentrations after
      in vitro infusions of human placenta at term].
AB  - Cefpirome (CPO) is a new parenteral cephalosporin with a wide antibacterial
      spectrum. In order to explore the possibility of using CPO in late pregnancy, we
      studied its placental transfer in vitro in a model of human placenta infusion.
      Mother-to-foetus in vitro transfer of CPO is high, similar to that of
      amoxicillin, with a placental clearance index of 0.20. A pharmacokinetic
      simulation based upon this result and data from literature suggests that CPO
      concentrations in foetal blood and amniotic fluid should be appropriate for the
      treatment of severe materno-foetal infections in late pregnancy. These
      preliminary results need to be confirmed by in vivo pharmacokinetic and clinical
      studies before recommending the use of CPO in late pregnancy.

PMID- 7808783
TI  - [Arguments in favour of the concept of critical threshold of accumulation of
      errors in cell death. Qualities and limits of this concept in cell aging].
AB  - The concept of critical threshold of error accumulation explains how a cell dies
      when it it confronted, abruptly or after a certain accumulation time, to a level
      of errors which is not sustainable anymore for the cell. Arguments in favour of
      this concept will be developed, which have mostly arose from the study of the
      cellular system of free radical production and elimination but also from the
      system of free energy production and utilisation. On one hand, this concept
      cannot explain how the level of errors can increase during normal ageing, in
      which cell death is not necessary involved. On the other hand, this concept can
      be a basis to explain the occurrence of some age-related pathologies where the
      relative resistance of the various cell types constituting an organ to intense
      stresses can be responsible for the occurrence of dysfunctions in this organ. The
      main point is that this concept takes into consideration the relative level of
      the defence systems confronted to the stress. Such a consideration of the
      cellular defence systems constitutes the basis for a global theory of cellular
      aging explaining how the level of errors can progressively increase with time,
      spontaneously of after intense non lethal stresses.

PMID- 7808784
TI  - [Critical review of theories on cell aging. From Hayflick's basis concept to the
      concept of critical threshold of accumulation of errors].
AB  - The goal of this review of the theories of cellular ageing is first to
      distinguish the theories on the basis of logical criteria following the
      dichotomies genetic/environmental and deterministic/stochastic. The second
      purpose is to show, from such criteria, that these theories can be integrated in
      a more general concept, which is the concept of critical threshold of error
      accumulation, taking into account the protective role of defenses systems
      avoiding a quick increase in the level of intracellular errors.

PMID- 7808785
TI  - [Methicillin resistant Staphylococcus aureus and glycopeptides (vancomycin,
      teicoplanin): in vitro selection of resistance].
AB  - By repeated and successive treatments of five strains of methicillin-resistant
      Staphylococcus aureus with sub-inhibitory concentrations of vancomycin and of
      teicoplanin, the authors have confirmed that selection of resistant strains could
      be obtained more easily with teicoplanin than with vancomycin. Moreover, we have
      shown that treatments with subinhibitory concentrations of teicoplanin could also
      influence the activity of vancomycin, although the strains have never been in
      contact with the latter antibiotic. This could account, at least in part, for the
      downhill evolution of the activity of glycopeptides against staphylococci,
      observed this last years. Indeed, the efficacy of these antibiotics upon which
      treatment of severe infections due to multiresistant staphylococci relies, is
      lowering. Considering the challenge, this risk is worth being not only evaluated
      by a reinforced epidemiologic surveillance, but also limited by more severe
      criteria for the prescription and the follow-up of treatments with glycopeptides.

PMID- 7808786
TI  - Cross resistance relevance of the chemical structure of different anthracyclines
      in multidrug resistant cells.
AB  - Positively charged doxorubicin (DOX) and non-positively charged anthracyclines,
      aclarubicin (ACR) and morpholino-carminomycin (KRN 8602), have been investigated
      with respect to pharmacological parameters, cytotoxicity, DNA damage and repair
      in DOX-sensitive and -resistant murine and human cells. Friend leukemia cells
      (FLC) resistant to high concentrations of doxorubicin (DOX-RFLC3) or daunorubicin
      (DNR-RFLC3) (1771 and 1543 fold resistance respectively) express less than 10
      fold resistance to aclarubicin (ACR). In these cells, the intracellular
      accumulation of ACR is similar in sensitive and resistant cells. Resistance to
      ACR was not observed in either DOX-RFLC1 or DNR1 with a lower level of resistance
      (27 fold). Increased expression of a 170,000-dalton surface antigen (gp-170) was
      found to be correlated with the level of resistance. However, when the selective
      agent in ACR, despite the low level of resistance (2.8 fold) both high expression
      of gp 170 and resistance to DOX (77 fold) or DNR (62 fold) are observed. It is
      assumed therefore that induction of multidrug resistance phenotype can be
      achieved by compounds which do not display cross resistance with DOX or DNR.
      Reduced levels or absence of cross-resistance can be related to the electrical
      charge of the compound. This assumption is supported by further studies on DOX
      sensitive or -resistant human K562 cells exposed to another non-positively
      charged anthracycline, KRN 8602. In the continuous presence of drug, K562/DOX
      were less resistant to KRN 8602 (2.9 fold) than to DOX (31 fold). After short
      time exposure followed by growth in drug-free medium, absence of cross-resistance
      to KRN 8602 has been observed in K562/DOX. Furthermore, accumulation experiments
      showed that high intracellular drug concentrations were rapidly achieved (within
      15 min) in both DOX-sensitive and -resistant cells. In cells exposed to DOX, DNA
      single-strand break (DNA-SSBs) frequencies were related to time and drug
      concentration while those produced by KRN 8602 or ACR were maximal after short
      time incubation. DNA-SSBs produced by these anthracyclines are not repaired when
      cells are incubated in drug free medium. In DOX resistant cells, DNA-SSBs
      produced by DOX were repaired whereas those produced by ACR or KRN 8602 were not.
      It is suggested, therefore, that absence of cross resistance to various
      anthracyclines is related to differences in the chemical electrical charge, which
      may influence drug accumulation and DNA repair in resistant cells.

PMID- 7808787
TI  - Chronotherapy of cancer: biological basis and clinical application.
AB  - Chronotherapy-administration of drugs according to biological rhythms-has
      recently followed a development similar to that of new drugs. Clinical phase I,
      II and III trials could reliabily be performed thanks to the avialability of
      specific tools for chronotherapy, e.g. programmable-in-time-pumps. In
      standardized and selected mice or rats, the toxicity of approximately 30
      anticancer agents (anthracylines, Pt complexes, fluoropyrimidines, nitrosoureas,
      as well as TNF, IL-2 ...) varied 2 to 10 fold according to drug dosing time along
      the 24 h time scale, as a result of endogenous circadian rhythms. Dosing-time
      dependent changes in pharmacokinetics or tissue uptake of drug do not suffice to
      explain 24 hr rhythms in drug pharmacodynamic effects. Thus, cellular rhythms in
      target tissues, including enzymatic activities, reduced glutathione, cell
      division cycle, ... appear as the major mechanisms of rhythms in the cytotoxicity
      of cytostatic compounds. These "peripheral" mechanisms are coordinated or reset
      by central biological clocks. In cancer patients, the continuous infusion of 5
      fluorouracil, adriamycin or vindesine at a constant rate resulted in large 24-hr
      changes in plasma drug levels. Mechanisms involve circadian changes in drug
      metabolism (e.g., dehydropyrimidine dehydrogenase for 5-FU), disposition (blood
      flow) or excretion (urine output). Extrapolation of times of least toxicity from
      nocturnally-active rodents to diurnally-active patients has been attempted
      through referring them to the sleep-wakefulness cycle of the considered species.
      Chronotherapy has allowed to significantly decrease drug toxicity and/or increase
      dose intensity of adriamycin, fluorouracil, FUdR, oxaliplatin and alpha
      interferon.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7808788
TI  - Telomerases.

PMID- 7808789
TI  - DNA topoisomerases and topoisomerase inhibitors.
AB  - DNA topoisomerases are ubiquitous nuclear enzymes, essential for several steps of
      DNA metabolism. They have recently been shown to be specific targets of a number
      of anticancer agents. In this review are discussed the most recent discoveries in
      the physiology and the molecular biology of DNA topoisomerases, and the mechanism
      of interaction with drugs. In addition, alterations of DNA topoisomerases are
      also described, as potential responsible of drug resistance.

PMID- 7808790
TI  - p53 expression in human renal cell carcinoma: an immunohistochemical study and a
      literature outline of the cytogenetic characterization.
AB  - In this study both the incidence and pattern of p53 over-expression in various
      histological subtypes of a series of 36 cases of renal cell Grawitz carcinoma,
      partially studied in a previous paper, were analyzed. This series consisted of
      these histologic subtypes: clear cell non papillary (18 cases), clear cell
      papillary (2 cases), granular cell (5 cases), mixed (clear and granular cell) (9
      cases) and spindle cell (2 cases). At present, our aim was, firstly, to see which
      were the best technical conditions for detection of p53 in the available paraffin
      embedded tumor specimens, using several antibodies, specific for various
      epitopes; secondly, to investigate if some relation might exist between this
      expression and the histological features of these tumors. Twenty-five per cent
      (9/36 cases) resulted p53 immunoreactive, the highest percentage being
      represented in the papillary clear and granular cell carcinomas; low expression
      was detected in 11 cases (30%) and no reactivity in 16 cases (44%). Neither
      technical or dilution modifications proved to transform these latter results;
      however, detection was maximal using the CM-1 polyclonal rabbit antiserum. Thus,
      in RCC, expression of p53, analyzed in the light of the cytogenetic
      characterization through a literature review, resulted at low frequency. This
      finding means that mutation of the p53 gene are not frequent in the neoplastic
      transformation in RCC. Nevertheless, in spite of the small number of cases and of
      the short follow-up period of this study, detection of p53 positivity in tumors
      with either high grade and stage or high proliferative activity could suggest
      that p53 mutations lead to tumors of a more aggressive type.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7808791
TI  - Nodular basement membrane deposits in breast carcinoma and atypical ductal
      hyperplasia: mimics of collagenous spherulosis.
AB  - Collagenous spherulosis is characterised histologically by the accumulation of
      hyaline globules containing basement membrane components. Originally described in
      the breast, it has also been found in skin and salivary gland neoplasms. In the
      breast it has hitherto always been associated with benign disease and reports
      have asserted that this is invariably the case, cautioning against the diagnosis
      of malignancy when the condition is seen. We present here five cases with similar
      appearances to collagenous spherulosis in routine histology and
      immunohistochemistry, and ultrastructural studies in one of them, in which the
      condition was not associated with simple benign breast disease. Two of the cases
      were associated with invasive carcinomas of unusual histological types, one with
      intracystic papillary carcinoma, one with comedo ductal carcinoma-in-situ and one
      with atypical ductal hyperplasia. We suggest that appearances similar to
      collagenous spherulosis can be associated, either through being formed by a
      lesion or by collision, with malignancy and warn that on encountering the lesions
      the pathologist must not assume, as suggested in previous accounts, that it
      denotes a benign process. This is an important observation since collagenous
      spherulosis is likely to be encountered more frequently in the range of lesions
      biopsied in national breast screening programs.

PMID- 7808792
TI  - Nm23 protein expression in thyroid neoplasms.
AB  - The nm23 gene production has been heralded as a suppressor of metastasis in many
      human tumours but it is not clear at which stage in the metastatic process nm23
      protein exerts its effect. The aim of this study was to test whether nm23 protein
      is associated with occurrence or category of angioinvasion. We have made use of
      the well documented fact that follicular carcinoma of the thyroid may show
      vascular invasion whereas papillary carcinomas may metastasis via the lymphatics.
      65 thyroid tumours (20 follicular adenomas, 22 papillary carcinomas, 23
      follicular carcinomas) were stained for nm23 protein using an immunopurified
      polyclonal antibody. Nm23 protein status showed no correlation with category of
      thyroid tumour. This is indirect evidence that nm23 does not suppress metastasis
      by influencing vascular invasion in this tumour type.

PMID- 7808793
TI  - HPV and p53 in urinary bladder carcinoma.
AB  - We report a study on human papilloma virus (HPV) and p53 protein in 18 cases of
      urothelial carcinoma grade 1, 2 and 3. The presence of HPV has been correlated to
      the p53 protein expression, as this virus, once integrated in the cell nuclei,
      seems to cause the alteration of some genes expression, involved in the cell
      cycle regulation, like p53. One case of urothelial papillary carcinoma grade 2,
      infiltrating the lamina propria, resulted to be positive for HPV type 31/33/51
      and for p53 protein. Our data suggest that HPV type 31/33/51 may have played a
      role in the pathogenesis of this neoplasia causing an alteration of p53 gene.

PMID- 7808794
TI  - [Aids-related cerebral lymphoma. Pathologic and immunohistochemical study of 19
      cases].
AB  - We studied 19 cases of AIDS-related cerebral lymphomas, 15 of which are primary,
      and 4 secondary to systemic lymphoma. Eighteen cases are classified as non
      Hodgkin's B cell lymphomas; in 1 case, an anaplastic large cell lymphoma coexists
      with systemic Hodgkin's disease. High-grade histologic types predominate
      (centroblastic, immunoblastic and immunoblastic plasmocytoid). One case of
      angiotropic lymphoma is included solely localized to the brain. We describe
      clinical and radiological features, gross, microscopic and immunophenotypic
      appearances. Other HIV-related associated diseases of the central nervous system
      are also considered.

PMID- 7808795
TI  - Origin of bronchial and pulmonary elastic fibers and their role in some
      pathological events.
AB  - The purpose of this contribution is to place a higher value on the existence of a
      turn-over of bronchial and pulmonary elastic fibers: the former would derive from
      the smooth muscle cells of the bronchial wall, the latter from the interstitial
      myofibroblasts of the alveolar septa. The reduction of the number of the elastic
      fibers in the bronchial wall during chronic atrophic bronchitis depend on the
      atrophy of the bronchial smooth muscle cells; in the alveolar septa the
      hyperplasia of the elastic fibers during pulmonary fibroses depend on the
      myofibroblastic proliferation, while the reduction of the elastic fibers number
      during pulmonary enphysema depend on the reduction in the number of
      myofibroblasts.

PMID- 7808796
TI  - [Monoclonal gammopathies: differential diagnosis with bone marrow biopsy].
AB  - Aim of the present study is to examine the morphological aspects of monoclonal
      gammopathies (GM) detectable by bone marrow biopsy. With reference to Multiple
      Myeloma (MM), the more important disease of this group from a clinical
      standpoint, other conditions will be later evaluated. Particular attention will
      be given to Monoclonal Gammopathy of Undetermined Significance (MGUS) that still
      today is characterized by wide shadows concerning both ethiology and evolution
      significance.

PMID- 7808797
TI  - B cell colony assay improves the sensitivity of the cytogenetic analysis in
      common acute lymphoblastic leukemia.
AB  - The recognition and identification of subtle chromosomal changes in leukemic
      cells has greatly been facilitated since the advent of high-resolution banding
      techniques. However efficient utilization of these methods is often hampered by
      the paucity of leukemic cells during clinical remission, the variability of cell
      cycle length and tissue culture conditions. Therefore the detection of minimal
      residual disease in acute lymphoblastic leukemia by cytogenetic methods requires
      a preselection of material to be examined. In this preliminary report analyzable
      metaphases could be obtained in cultured cells from a colony assay for malignant
      peripheral B cell progenitors, whereas in marrow samples direct or 24 hours G
      banding technique had failed to reveal metaphases in common Acute Lymphoblastic
      Leukemia patients during complete remission. It is believed that in common Acute
      lymphoblastic Leukemia patients this B cell colony assay permits the clonal
      expansion of residual circulating cells linked to malignant clone that are not
      detectable by classic hematologic and cytologic methods. In addition, this
      culture procedure substantially improves the sensibility of cytogenetic approach
      to the study of minimal residual disease in acute lymphoblastic leukemia during
      complete remission.

PMID- 7808798
TI  - [Granulomatous hepatitis in a hospital population in southern Italy].
AB  - In a southern Italy hospital, in five years 1523 liver biopsy specimens have been
      performed and histologically examined. Granulomas are found in specimens from 15
      patient (1%). They are seven females and eight males with an average age of 57
      years (range 43-71). Seven of the 15 specimens are Menghini-type percutaneous
      needle, five are surgical and three are laparoscopic bioptic specimens. Four
      patients are correlated with infectious diseases: 2 with hepatitis C virus (HCV),
      1 with hepatitis B virus (HBV) and 1 with Mycobacterium Tuberculosis. In three
      patients the diagnosis is primary biliary cirrhosis (PBC), in two sarcoidosis, in
      other two pseudosarcoid reaction to abdominal tumours (a gall-bladder cancer and
      a non-Hodgkin lymphoma of the stomach). Finally there are 2 lipogranulomas, 1
      foreign-body granuloma and 1 cholesterin granuloma. This work underlines the high
      prevalence in our series of PBC and sarcoidosis in the etiology of hepatic
      granulomas and the high frequency of patients with markers of HCV or HBV in
      granulomatous hepatitis.

PMID- 7808799
TI  - Hypertrophic motor and sensory neuropathy type I (Charcot-Marie-Tooth disease):
      ultrastructural study of sural nerve biopsy in members of a family.
AB  - Three members of a family with a hereditary neuropathy were studied. Light,
      electron microscopy and teasing of isolated fibres were performed. The findings
      confirmed the clinical and electrophysiological hypothesis of hypertrophic form
      of Charcot-Marie-Tooth disease. Hypertrophy of Schwann cells with the formation
      of onion bulb figures as the most evident ultrastructural feature, besides
      demyelination, remyelination and mild axonal degeneration. Recent data about the
      genetic transmission and pathogenesis of the hereditary motor and sensory
      neuropathies (HMSN) are discussed.

PMID- 7808800
TI  - [Histopathologic findings in CD1 albino mice infected with Plasmodium berghei in
      pregnancy. Experimental model for pathology of the feto- placental unit in
      malaria].
AB  - Three study groups of pregnant CD1 albino mice were inoculated intraperitoneally
      with Plasmodium berghei on the 6th (Group I), 13th (Group II) and 18th (Group
      III) day of gestation. Two control Groups were included, one of non pregnant mice
      (Group IV) and the other of pregnant non inoculated mice. Group IV was inoculated
      in the same day of group I. All mice of these two Groups died. Of the 20 mice in
      Group II 8 died, 7 delivered prematurely and 5 gave birth of low birth weight
      offspring. The 15 mice in Group III delivered normally with only 4 low birth
      weight offspring and no deaths. Histological examination revealed total placental
      necrosis, resorption of the products of conception and widespread foci of hepatic
      necrosis, malarial pigment accumulation in Group I. Such changes were also
      present in 8 mice of Group II, but the remainder of the Group retained the
      product of conception, had marked morphological changes in the placenta and
      moderate focal hepatic necrosis and malarial pigment accumulation. Group III had
      mild placental changes and moderate pigment accumulation. The products of
      conception displayed marked hepatic hematopoiesis in Group II while it was
      moderate in Group III. No parasitized red cells were observed in the fetal
      circulation. The stage of gestation at which the malarial infection was
      contracted was decisive. Malarial infection does not cross the placental barrier
      so its pathogenetic effects are felt in the maternal circulation with variable
      effects on the products of conception.

PMID- 7808801
TI  - Intraoperative cytology in otorhinolaryngologic and cervical pathology.
AB  - Intraoperative Cytology (I.C.) is widely acknowledged to be not only a valuable
      adjunct to frozen sections (F.S.) but also, in a high percentage of cases, a
      valid technique in itself when it is in agreement with macroscopic evaluation. In
      a study of 211 otorhinolaryngologic and cervical cases, we registered a 96.20%
      correspondence between I.C. diagnosis and definitive diagnosis, as against a
      95.26% correspondence for F.S. diagnosis was deferred in 3.31% of cases examined
      by I.C. and only one false negative occurred. I.C. is simple, rapid, reliable and
      inexpensive. On the basis of our experience, we maintain that this technique is
      not only of great value as a supplement to F.S. but that in a high percentage of
      cases it can actually substitute frozen sections.

PMID- 7808802
TI  - Chondroid metaplasia in the tunica media of the aorta in dogs submitted to
      saphenous vein aorto-cava by-pass.
AB  - We submitted twelve dogs to aorto-superior vena cava by-pass with saphenous vein.
      Six months later, all dogs had developed areas of chondroid metaplasia in the
      tunica media of the aorta, near the area of anastomosis. Three dogs also had bony
      metaplasia. The Foci of metaplasia had no relation to sutures. This lesion begins
      with a build-up store of glycosaminoglycans in the tunica media. Later, elastic
      fibers show a fenestration and dissolution, while chondrocytes replace smooth
      muscle fibres. We suggest that the rupture of the vasa vasorum during operation
      and the traction and pulsation of the by-pass over the area of suture could be
      the cause of this direct metaplasia.

PMID- 7808803
TI  - Ag-NOR counting for differentiation of follicular thyroid tumours.
AB  - According to the histological typing system of thyroid tumours adapted by the
      World Health Organisation follicular tumours are classified as follicular
      adenomas and follicular carcinomas. The most important diagnostic criterion for
      follicular carcinoma is the evidence of vascular and/or capsular infiltration.
      The aim of this work was to verify the Ag-NOR counting method for the diagnosis
      of thyroid tumours. From the material of the experiment on mice that drunk
      thyrostatic (1.2% NaCIO4) and were irradiated 10 histologically normal thyroids,
      10 showing hypertrophy and hyperplasia, 8 follicular adenomas and 10 follicular
      carcinomas were used. Thyroid glands were impregnated with the silver to present
      Ag-NORs. The average numbers of Ag-NORs per nucleus (Ag-NOR/nucleus) for each
      group were determined. The results showed that the method of counting Ag-NOR can
      be used to differentiate among thyroid tumours.

PMID- 7808804
TI  - Solitary neurofibroma of the mesentery: a case report with immunohistochemical
      study of extracellular matrix.

PMID- 7808805
TI  - Clear cell hepatocellular carcinoma treated with liver transplantation.
AB  - We report a case of a 35-year-old female who underwent total hepatectomy and
      liver transplantation for a diffuse clear cell variant of hepatocellular
      carcinoma in non-cirrhotic liver. Preoperative clinical evaluation showed no
      extrahepatic metastatic involvement. However, scheletal metastases of the tumour
      were detected five months later. Although clear cell variant is generally
      considered to run a relatively favorable course, this case proved rapidly
      progressive and seems therefore to be a debatable candidate for liver
      transplantation among primary hepatic cancers.

PMID- 7808806
TI  - Primary ovarian pregnancy. A case report.
AB  - A primary ovarian pregnancy was diagnosed in a patient with intrauterine device.
      Primary ovarian pregnancy which is a rare form of ectopic pregnancy, was reviewed
      according to etiology, pathogenesis and improvements in diagnosis and therapy. In
      this article, our case was multiparous and used intrauterine device for 5 years.
      Ovarian pregnancy was diagnosed before operation. This diagnosis was verified
      histologically and she was treated by oopherectomy.

PMID- 7808807
TI  - Metastatic follicular carcinoma of the thyroid simulating sarcoma of the limb.
AB  - We report a case of metastatic follicular carcinoma of the thyroid presenting
      with clinical and radiological manifestations simulating a sarcoma of the humeral
      region. Thus left arm amputation was performed. Histopathological examination
      revealed the condition.

PMID- 7808808
TI  - [Adenocarcinoma of the large intestine associated with retroperitoneal
      ganglioneuroblastoma. Report of a case].

PMID- 7808809
TI  - [Fibrous hamartoma in childhood].
AB  - Is a rare soft tissue benign tumor usually appearing during the first two years
      of life, often occurring in axillary or upper arm region subcutaneous tissue.
      Surgery is the treatment of choice. The lesion histologically consists of three
      different tissue elements: dense mature fibrocollagenous, loose immature myxoid
      mesenchymal and mature adipose tissue. A case of fibrous hamartoma of infancy
      with the usual clinical characteristics, but with particular microscopic features
      due to the abundance in fibrocollagenous and scarcity of myxoid tissue, is
      described. The results of the immunohistochemical and ultrastructural study on
      the same patient are reported. The differential diagnostic problems are
      discussed.

PMID- 7808810
TI  - [A rare case of bilateral metastasis in the cerebellopontine angle].
AB  - A rare clinical and anatomopathological observation of bilateral pontocerebellar
      angle metastases due to gastric carcinoma is presented. The pathogenetic
      mechanism of this exceptional localization is proposed on the base of the
      literature data.

PMID- 7808811
TI  - [Reye's syndrome and hemophagocytic histiocytosis in a 16-month-old boy: is there
      a possible common etiopathogenetic basis?].
AB  - The Authors report a case of Reye's syndrome associated with an hemophagocytic
      histiocytosis in a 16-month-old baby. The vaccination against measles, mumps and
      rubella administrated 15 days before the onset of symptoms is suggested as the
      etiologic factor of both diseases. The Authors believe that the vaccine, composed
      of alive viruses was responsible of immunodepression and, as a common viral
      infection, of Reye's syndrome and hemophagocytic histiocytosis in the child
      constitutionally predisposed.

PMID- 7808812
TI  - A pediatrician's view. Parasitoses in pediatric practice.

PMID- 7808813
TI  - An overview of parasitic diseases in children in the United States: what's old?
      What's new? Where's help?

PMID- 7808814
TI  - Febrile illness caused by parasites.
AB  - Febrile patients in whom a parasitic etiology is suspected can be classified
      broadly into two categories for the purpose of diagnostic evaluation based on the
      presence or absence of accompanying eosinophilia. Generally, the absence of
      eosinophilia indicates a protozoan etiology while the presence of eosinophilia is
      associated with tissue-invasive helminthic infections. The history and physical
      examination often points to a specific diagnosis that can be confirmed by
      appropriate laboratory tests.

PMID- 7808815
TI  - Eosinophilia caused by parasites.
AB  - Eosinophilia is defined as an absolute count of > 500 eosinophils per mm3 of
      peripheral blood. Eosinophilia is associated with many disorders, limiting its
      usefulness as a diagnostic tool in screening expatriates for parasite infections.
      In addition, only tissue-invasive helminthic parasites cause eosinophilia, which
      limits its general application as a screening tool for parasitic infections.
      Because eosinophilia may resolve spontaneously over time, the life cycle of
      parasites must be considered when evaluating eosinophilic patients, and repeated
      stool examinations or appropriate serology may be necessary to make the correct
      diagnosis. Future work on the risks associated with subclinical parasite
      infections would be helpful to place eosinophilia and other screening tests in
      proper perspective. Referral of difficult cases to specialists in travel medicine
      should be considered because detailed information about the geographic
      distribution and life cycle of helminthic parasites is often crucial to making
      the correct diagnosis.

PMID- 7808816
TI  - Parasitic causes of diarrhea.

PMID- 7808817
TI  - Parasitic infections of the central nervous system.

PMID- 7808818
TI  - Parasitic infestations of the skin.

PMID- 7808819
TI  - Respiratory distress caused by parasites.
AB  - Parasitic etiologies of pulmonary symptoms generally represent some degree of
      immunocompromise or occur as uncommon presentations of common parasitic
      infections. In regions where HIV infection is more prominent, PCP probably will
      be the most common parasitic respiratory disease seen. In geographic regions
      where helminthic infections are more common, patients with respiratory symptoms
      and eosinophilia probably will be seen more often and require a search for a
      specific etiology. In more rare circumstances, travel to an endemic area may
      suggest a more exotic parasitic etiology for respiratory symptoms.

PMID- 7808820
TI  - The SEC receptor: a possible link between neonatal hepatitis in alpha 1
      antitrypsin deficiency and Alzheimer's disease.

PMID- 7808821
TI  - Long-term effects of unsaturated fatty acid dominance on the release of free
      radicals in the rat.
AB  - The aim of this study was to investigate the effects of an abundance of
      unsaturated fatty acids, hyperoxia, and vitamin E on free radical formation in
      vitamin E-deficient rats. The excess of unsaturated fatty acids was achieved by
      i.v. administration of a lipid emulsion (Intralipid). To assess free radical
      formation, we measured the autooxidative susceptibility of red blood cells (AOS)
      and the thiobarbituric acid reacting substrates (TBARS) in LDL and HDL.
      Intralipid significantly increased all the measured parameters compared with
      controls (AOS: 1385 +/- 73 versus 1056 +/- 55; LDL-TBARS: 4955 +/- 422 versus
      1050 +/- 33; HDL-TBARS: 6855 +/- 573 versus 1033 +/- 26 nmol TBARS/mmol).
      Hyperoxia alone increased AOS more than Intralipid alone, whereas LDL- and HDL
      TBARS concentrations were affected less by hyperoxia than lipid emulsion. The
      combination of hyperoxia and Intralipid was most effective in raising all
      measured parameters (AOS: 2285 +/- 141; LDL-TBARS: 6716 +/- 318; HDL-TBARS: 14614
      +/- 1000 nmol TBARS/mmol). Vitamin E completely prevented the increase in AOS,
      LDL-TBARS, and HDL-TBARS without fully reversing the increase in free radical
      formation caused either by Intralipid or by the combination of hyperoxia and
      Intralipid. These findings suggest that vitamin E supplementation is beneficial
      to counter increased free radical formation, such as that in response to
      hyperoxic attacks or lipid-containing parenteral nutrition, which is frequently
      encountered in the treatment of premature infants.

PMID- 7808822
TI  - Plasma xanthine oxidase activity and lipid hydroperoxide levels in preterm
      infants.
AB  - Ischemia-reperfusion injury may affect morbidity and mortality in preterm and
      asphyxiated term infants. Reoxygenation of hypoxic tissues leads to the formation
      of free oxygen radicals by xanthine oxidase that may induce lipid peroxidation,
      enzyme inhibition, and DNA strand breakage. We measured arterial cord blood
      samples from 36 healthy term infants for baseline values and arterial blood
      sampled at 1 and 4 h after birth from 45 preterm infants admitted for intensive
      care for serial estimates of plasma xanthine oxidase activity and lipid
      hydroperoxide levels. Mean +/- SEM plasma xanthine oxidase activity in cord blood
      of term infants was 2.3 +/- 0.4 mU/mL and lipid hydroperoxide levels were 2.6 +/-
      0.3 nmol/mL. Eighteen of the 45 preterm infants met the criteria defining poor
      outcome (poor outcome group) and had lower umbilical arterial pH and base excess
      than the 27 preterm infants in the control group. Mean plasma xanthine oxidase
      activity increased from 2.7 +/- 0.4 at 1 h to 4.7 +/- 0.6 mU/mL at 4 h of age (p
      < 0.001) in the poor outcome group and decreased from 2.1 +/- 0.3 to 1.1 +/- 0.2
      mU/mL (p = 0.004) in the control group. Lipid hydroperoxide levels in the poor
      outcome group increased from 2.8 +/- 0.6 nmol/mL at 1 h to 4.3 +/- 0.6 nmol/mL at
      4 h of age (p < 0.001) and decreased from 2.1 +/- 0.6 to 1.6 +/- 0.2 nmol/mL (p =
      0.008) in the control group. At 4 h of age, xanthine oxidase activity and lipid
      hydroperoxide levels were significantly higher in the poor outcome group than in
      the controls (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7808823
TI  - Moderate carnitine depletion and long-chain fatty acid oxidation, exercise
      capacity, and nitrogen balance in the rat.
AB  - Carnitine plays a central role in lipid metabolism by transporting long-chain
      fatty acids into the mitochondria for beta-oxidation. Reduction of carnitine
      concentration does not automatically imply that functional carnitine deficiency
      exists with direct consequences on energy metabolism. In our experimental model,
      we reduced tissue concentrations of carnitine to levels that are comparable to
      those in patients with various metabolic disorders with secondary carnitine
      deficiency and did a study on the in vivo effects of moderate carnitine depletion
      on palmitate oxidation, exercise capacity, and nitrogen balance. Thirty rats were
      divided into a carnitine-depleted group (group I) and pair-fed controls (group
      II). Carnitine depletion resulting in a 48% reduction of tissue carnitine
      concentrations was induced by feeding ad libitum a carnitine-free oral diet
      consisting of parenteral nutrition solutions. Palmitate oxidation was measured by
      collecting expired 14CO2 after an intraperitoneal injection of [1-14C]palmitate,
      and exercise capacity was determined by having the rats swim to exhaustion.
      Despite the 48% depletion of carnitine in serum, muscle, and liver, there were no
      differences in cumulative palmitate oxidation in 3 h (group I, 40 +/- 7%; group
      II, 37 +/- 9% of injected activity), swimming time to exhaustion (group I, 8.1 +/
      2.8 h; group II, 7.7 +/- 3.6 h), or nitrogen balance (group I, 1.1 +/- 0.5 g of
      nitrogen/kg/d; group II, 1.2 +/- 0.5 g of nitrogen/kg/d). We conclude that
      carnitine depletion of 48% has no effect on palmitate oxidation, exercise
      capacity, or nitrogen balance in the rats studied.

PMID- 7808824
TI  - Hyperglycemia-induced hyperinsulinemia decreases maternal and fetal plasma
      protein C concentration during ovine gestation.
AB  - To determine effects of diabetic gestation on plasma concentration of the
      coagulation regulatory protein, protein C, pregnant ewes were given glucose
      infusions to raise plasma glucose to twice baseline concentration or insulin
      infusions to lower glucose concentration to half baseline value. Control animals
      received no infusions. Concentrations of protein S, factor X, and antithrombin
      III were determined for comparison. Concentrations of glucose, insulin, and those
      above were determined thrice weekly for 2-9 wk. Short-term (8-12 h) infusions of
      glucose or insulin were performed to isolate their effect on concentration of
      protein C. Results were analyzed using a two-tailed t test, and protein C
      concentrations were further analyzed using a full linear mixed-effects model. In
      long-term infusions, hyperglycemia-induced hyperinsulinemia (mean insulin
      concentration 141 microU/L) exerted negative effects on maternal concentrations
      of protein C [0.69 U/mL, n (number of samples) = 32, experimental versus 0.97
      U/mL, n = 157, control], protein S (0.86 U/mL, n = 31, experimental versus 1.04
      U/mL, n = 109, control), and factor X (0.89 U/mL, n = 31, experimental versus
      1.04 U/mL, n = 109, control); it exerted no effects on antithrombin III (1.05
      U/mL, n = 23, experimental versus 1.04 U/mL, n = 32, control). The fetal lamb did
      not respond to chronic moderate hyperglycemia (mean 33 mg/dL) with a consistent
      change in insulin concentration (mean 10 versus 9 microU/mL): no coagulation
      protein changed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7808825
TI  - Effects of dietary alkylglycerols in lactating rats on immune responses in pups.
AB  - Alkylglycerols (AG) are glyceryl ether lipid and are present in human and cow's
      milk and the hematopoietic organs such as bone marrow, spleen, and liver. The
      biologic effects of AG include stimulation of blood leukocyte and thrombocyte
      production and activation of macrophage and anti-tumor activity. The present
      study was conducted to determine the effects of dietary AG in lactating rats on
      AG levels in milk and development of certain immune responses in the pups.
      Lactating rats were fed diets supplemented with various levels of AG. Milk
      samples were expressed from the dams and blood was collected from the pups on
      postpartum d 8, 16, and 24. Concentrations of AG in milk from the dams fed AG
      were significantly greater than those of the controls (p < 0.05). Peripheral
      blood granulocytes were significantly elevated in pups from the dams fed AG, but
      there were no differences in peripheral blood lymphocyte numbers. Plasma levels
      of immunoglobulins were significantly greater for IgG (p < 0.01) and IgM (p <
      0.001) in pups from the dams fed AG than in the control pups. The supplementation
      of AG in the diets of lactating dams significantly elevated AG levels in the
      milk, and the increased AG in the milk subsequently stimulated certain immune
      responses in the pups.

PMID- 7808826
TI  - Semipermeable dressings improve epidermal barrier function in premature infants.
AB  - Infants of less than 32 wk gestation have a defective epidermal barrier, with
      increased skin permeability and transepidermal water loss (TEWL). We studied the
      effect of a nonadhesive semipermeable dressing on the epidermal barrier of
      premature infants and on fetal skin transplanted to nude mice. Fifteen infants
      with a mean estimated gestational age of 27.7 wk and 16 human fetal skin grafts
      (estimated gestational age, 23-26 wk) transplanted to eight nude mice were
      studied. One lower leg (or skin graft) was treated and the other left untreated
      as a control. In the infants, TEWL was measured on control skin and treated skin
      (both through the dressing and after temporary dressing removal) on d 0, 1, 2, 4,
      and 7. Bacterial and fungal cultures were also performed. In the mice, TEWL and
      skin blood flow were measured on d 0, 2, and 4. Biopsies were obtained on d 4 for
      a cell proliferation assay, histology, and electron microscopy. Treated infant
      skin showed a consistently lower bacterial number and a significantly decreased
      TEWL (measured through the dressing). There was also a significantly lower TEWL
      on the treated side, measured after temporary dressing removal, on d 1, 2, 4, and
      7, documenting improved epidermal barrier function. The animal study revealed
      decreased TEWL and a nearly 2-fold greater d-4 keratinocyte proliferation (p =
      0.01) in treated skin and decreased blood flow on d 4 in control skin (p = 0.01).
      There was no significant difference in the volume density of membrane coating
      granules or the morphology of intercorneocyte spaces.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7808827
TI  - Somatotropic dysfunction in growth hormone-releasing hormone-deprived neonatal
      rats: effect of growth hormone replacement therapy.
AB  - In a previous work, we reported that passive immunization with anti-growth
      hormone-releasing hormone (GHRH) antibodies (GHRH-Ab) in neonatal rats caused
      disruption of somatotropic function that was still present 60 d posttreatment. We
      studied the reversibility of this condition by growth hormone (GH) replacement
      therapy. Neonatal rats received GHRH-Ab (50 microL/rat, s.c.) or normal rabbit
      serum every second day from birth up to postnatal d 10 and received hGH (0.4
      microgram/g body weight, s.c., b.i.d.) or vehicle in a 2 x 2 factorial design.
      Animals were studied on d 11 of age. In GHRH-Ab-treated rats, GH therapy 1)
      counteracted the reduced body weight and low plasma IGF-I levels; 2) failed to
      modify the reduced pituitary weight and GH content; 3) further reduced the low
      plasma GH levels; 4) partially restored the defective GH responsiveness to GHRH;
      5) failed to modify the reduced hypothalamic somatostatin and increased GHRH gene
      expression in the hypothalamus; and 6) reverted the decreased pituitary
      somatostatin binding. Morphologic and morphometric evaluation of the pituitary
      gland from GHRH-AB+GH pups showed that the number of GH-labeled structures was
      lower than in normal rat serum-GH-treated pups, whereas the total GH
      immunoreactivity per unit surface, an index of intracellular hormone
      concentration, was slightly higher than in vehicle-GH or GHRH-Ab pups. As
      determined by electron microscopy, somatotropes from GHRH-Ab+GH pups had
      morphologic features of high cellular activity. It appears that in GHRH-deprived
      pups GH replacement therapy can normalize most but not all altered indices of the
      somatotropic function.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7808828
TI  - Final height and its predictive factors after renal transplantation in childhood.
AB  - A retrospective study is reported assessing final height (FH) and its predictive
      factors in 52 patients (31 male, 21 female) who underwent renal transplantation
      (RTx) before the age of 15 y. They received prednisone daily or on alternate days
      as well as azathioprine. The study period covered 20 y. FH remained below the
      third height percentile [height standard deviation score for chronologic age
      (hSDSCA) < -1.88] for most of these patients (77% males, 71% females). Median
      (range) FH was 165.0 (143.0-176.8) cm in males and 153.0 (135.0-168.4) cm in
      females. Median difference between FH and target height was 15.0 and 15.4 cm for
      males and females, respectively. For both sexes, the median hSDSCA was already
      below -1.88 at the start of the first hemodialysis, after which it decreased
      significantly until the first RTx. After RTx, there was no significant
      improvement of hSDSCA. The predictive factors for FH were determined by
      evaluating various factors simultaneous in a multiple regression analysis. This
      analysis provided a regression equation for predicting FH. A higher hSDSCA at the
      time of the first RTx and alternate-day versus daily prednisone therapy both had
      a significantly positive influence on FH, whereas a longer duration of reduced
      GFR (< 50 mL/min/1.73 m2) had a significantly negative effect on FH. Other
      factors such as age or bone age at first RTx, primary renal disease, duration of
      initial dialysis, repeat RTx, and the cumulative dose of prednisone did not
      influence FH significantly. In conclusion, 71-77% of patients that received their
      first renal transplant before the age of 15 ended up with severely short adult
      stature. Optimization of the hSDSCA at first RTx appears very important. Long
      term administration of prednisone on alternate days would then result in optimal
      FH, particularly if the GFR remains above 50 mL/min/1.73 m2.

PMID- 7808829
TI  - Similar gastric emptying rates for casein- and whey-predominant formulas in
      preterm infants.
AB  - Casein-predominant infant milk formulas have been speculated to predispose to
      lactobezoar formation in preterm infants due to delayed gastric emptying. There
      have been, however, no prospective studies to prove this possibility. In a
      randomized, double-blinded, prospective study, we tested the hypothesis that
      preterm infants fed casein-predominant milk formula have slower gastric emptying
      than infants fed whey-predominant formulas. Twenty preterm infants within the
      first 4 d of life were randomized to receive either the whey-predominant formula
      Similac Special Care (whey:casein ratio 60:40) or an experimental casein
      predominant formula (whey:casein ratio 18:82). Only the protein composition
      differed between the two formulas. The infants were fed the assigned study
      formula until they reached approximately 2200 g body weight when a gastric
      emptying scan was performed, using the designated study formula mixed with 25
      microCi of technetium-99 sulfur colloid. Gastric emptying was followed
      continuously for 2 h. Gastric emptying at 30, 60, 90, and 120 min was similar
      between the two study groups. The time for 50% gastric emptying was 64.9 +/- 12.3
      min for the infants fed the whey-predominant formula and 56.5 +/- 14.8 min for
      those fed the casein-predominant formula (p = 0.75). We conclude that the rate of
      gastric emptying in preterm infants fed casein-predominant formulas is similar to
      that in those fed whey-predominant formulas.

PMID- 7808830
TI  - Mesenteric blood flow velocity and its relation to circulatory adaptation during
      the first week of life in healthy term infants.
AB  - We investigated early postnatal changes of the mesenteric circulation and its
      relationship to the systemic circulation in two groups of newborn infants. Group
      I (n = 10) was studied before the first feeding at 1 h and preprandially at 6 and
      24 h. Group II (n = 10) was studied before the first feeding at 2 h of age and
      preprandially and postprandially at d 3, 4, and 5. Blood flow velocity was
      measured with ultrasound Doppler in the superior mesenteric artery (SMA), middle
      cerebral artery, subclavian artery, and aortic orifice for cardiac output (CO)
      calculations. Blood pressure and heart rate were monitored. SMA mean velocity
      (Vmean) decreased from 1 [0.33 +/- 0.07 m/s (mean +/- SD)] to 6 h (0.23 +/- 0.08
      m/s, p < 0.005) in group I, probably due to ductal steal, returning to the 1-h
      value at 24 h. In contrast, middle cerebral artery Vmean remained unchanged in
      the first 24 h. From d 3, SMA Vmean increased 92% postprandially, with no
      relation to increasing amounts of food. The postprandial increase in SMA Vmean
      was not associated with changes in CO and blood pressure; however, a fall in
      relative mesenteric vascular resistance suggested regional redistribution of CO.
      Middle cerebral artery Vmean increased from h 2 to d 3 with a further increase on
      d 4 (p < 0.01). This increase was associated with an increase in blood pressure.
      The relative fraction of CO to middle cerebral artery increased during the first
      days of life, suggesting a redistribution of blood flow to the metabolically
      active organs in the neonatal period.

PMID- 7808831
TI  - Molecular analysis of abnormal pyruvate dehydrogenase in a patient with thiamine
      responsive congenital lactic acidemia.
AB  - A patient who responded to thiamine therapy with reduction of lactate in the
      blood and cerebrospinal fluid and clinical improvement was studied. Cultured
      lymphoblastoid cells of this patient were found to show reduced activities of
      pyruvate dehydrogenase complex (PDHC) and pyruvate dehydrogenase, decreased
      affinity of PDHC for thiamine pyrophosphate, and defective activation of PDHC by
      pyruvate dehydrogenase phosphatase. PDHC deficiency in fibroblasts and biopsied
      muscle of this patient was also due to the decreased affinity of PDHC for
      thiamine pyrophosphate. A mutation in the E1 alpha subunit containing the
      thiamine binding site and serine phosphorylation site regulating the
      activation/inactivation of PDHC was characterized by the polymerase chain
      reaction and DNA sequencing. A single A-->G transition was identified at position
      131, resulting in the substitution of Arg-44 for His-44. This mutation must be a
      de novo mutation because it was not found in either parent's genomic DNA. In this
      study, we have obtained the first evidence at the molecular level for a mutation
      of thiamine-responsive PDHC deficiency.

PMID- 7808832
TI  - A portable dual energy x-ray absorptiometry technique for the measurement of bone
      mineral in preterm infants.
AB  - A dual energy x-ray absorptiometry technique has been developed for the
      measurement of bone mineral in preterm infants. Two films are taken of the
      infant's forearm using a standard mobile x-ray set on the ward at two x-ray
      energies. Included in the field of view is a double step wedge made of aluminum
      and Perspex. The images are digitized by viewing them on a light box with a TV
      camera. The bone mineral content in the forearm can then be mapped by the
      measurement of light intensity in matching pixels of the two films and comparison
      with the intensities in the step wedge. The bone mineral concentration in the
      radius, expressed as bone mineral per unit length (mg/mm), is calculated. The
      technique has been tested using phantoms of calcium hydroxylapatite set in a
      tissue equivalent material and in Perspex. It has been shown that the
      reproducibility of the technique is approximately 7% and that there is a
      systematic underestimate of bone mineral of about 17%. The technique has been
      shown to be linear up to a bone mineral concentration of 8 mg.mm-1. Longitudinal
      studies for 14 infants that show an initial 6-wk period of demineralization after
      birth with a subsequent mineralization phase are reported.

PMID- 7808833
TI  - Heart rate power spectrum and plasma catecholamine levels after postural change
      and cold pressor test.
AB  - During stress, low-frequency (0.01-0.15 Hz) heart rate power and plasma
      catecholamine levels increase in response to increased sympathetic efferent
      activity. To test the hypothesis that low-frequency heart rate power, a measure
      of sympathetic control of heart rate, directly correlates with plasma
      catecholamine concentrations during periods of increased sympathetic tone, we
      compared heart rate power spectral measures with antecubital vein norepinephrine,
      epinephrine, and dopamine concentrations during postural change and after cold
      pressor testing. We analyzed absolute levels and changes in mean heart rate,
      respiratory rate, blood pressure, heart rate power spectra, and concentration of
      norepinephrine, epinephrine, and dopamine in 14 healthy volunteers (seven
      female/seven male) after postural change and in six (three female/three male)
      during cold pressor testing. Postural change from supine to standing position
      resulted in increased heart rate [61 +/- 8 versus 83 +/- 11 (SD) bpm, p < 0.05],
      diastolic (68 +/- 7 versus 77 +/- 6 mm Hg, p < 0.05) and mean blood pressures (84
      +/- 6 versus 91 +/- 9 mm Hg, p < 0.05), norepinephrine concentration (2.09 +/-
      1.11 versus 3.23 +/- 1.62 nmol/L, p < 0.05), and low-frequency heart rate power
      (7.55 +/- 5.63 versus 33.79 +/- 23.55 bpm2, p < 0.05). High-frequency heart rate
      power, a measure of parasympathetic control of heart rate, decreased with
      standing (5.38 +/- 4.22 versus 2.94 +/- 2.69 bpm2, p < 0.05).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7808834
TI  - Effect of continuous negative extrathoracic pressure on respiratory mechanics and
      timing in infants recovering from neonatal respiratory distress syndrome.
AB  - Changes in respiratory mechanics and timing produced by continuous negative
      extrathoracic pressure (CNEP) of -0.6 kPa were assessed in 18 infants recovering
      from neonatal respiratory distress syndrome. The median gestational age was 28 wk
      (range 24-36 wk). All infants were recruited before discharge from neonatal
      intensive care and were measured at a median postnatal age of 58 d (range 10-127
      d) and a median weight of 2.67 kg (range 1.99-3.77 kg). All had been treated for
      respiratory distress syndrome; 11 were diagnosed as having chronic lung disease.
      At the time of the study, all infants were stable breathing room air. There was a
      significant decrease of the respiratory rate in all but one infant from 63.6 +/-
      10.0 to 49.3 +/- 9.1 breaths per min (mean +/- SD) during CNEP. This was
      predominantly due to a marked prolongation of the expiratory time. Passive
      respiratory mechanics were assessed using airway occlusion techniques. Whereas
      respiratory system compliance (Crs) did not change in the infants with a normal
      baseline measurement, there was a significant improvement of Crs in the 11
      infants with low Crs values in atmosphere: In the latter, all of whom were very
      low-birth-weight infants, Crs assessed by the multiple occlusion technique (mean
      +/- SD) corrected for body weight increased from 7.9 +/- 1.5 to 9.4 +/- 1.9
      mL.kPa-1.kg-1 in CNEP (p = 0.012). There was no consistent change in respiratory
      system resistance in this population of 18 infants.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7808835
TI  - Determinants of increased left ventricular output during in utero ventilation in
      fetal sheep.
AB  - A model of in utero ventilation was used to elucidate the mechanisms by which
      left ventricular (LV) output increases with the transition from a fetal to a
      neonatal circulation. Using a conductance catheter, LV volumes were measured in
      seven anesthetized, near-term fetal sheep. Pressure-volume data was recorded
      before and with oxygen ventilation and again after occlusion of the umbilical
      cord. Ventilation caused increases in LV end-diastolic volume measured in seven
      anesthetized, near-term fetal sheep. Pressure-volume data was recorded before and
      with oxygen ventilation and again after occlusion of the umbilical cord.
      Ventilation caused increases in LV end-diastolic volume (2.3 +/- 0.9 to 2.9 +/-
      0.6 mL/kg; p < 0.05), stroke volume (1.2 +/- 0.3 to 1.9 +2- 0.2 mL/kg; p <
      0.001), and ejection fraction (52.8 +/- 11.1 to 66.4 +/- 8.8%; p < 0.001).
      Contractile state, as assessed by end-systolic elastance, did not change during
      the transition. Heart rate also remained constant. Afterload, as assessed by
      effective arterial elastance, decreased from 1.80 +/- 0.37 to 1.04 +/- 0.33
      kPa/mL (p < 0.01). Occlusion of the umbilical cord did not result in any further
      change in hemodynamic parameters. Pressure-volume analysis revealed that a
      decrease in effective LV afterload and an increased LV end-diastolic volume are
      the major determinants of, and contribute comparably to, the profound increase in
      LV output with in utero ventilation. Enhanced contractility is not required for
      the increase in LV output to occur.

PMID- 7808836
TI  - Delayed ultrastructural lung maturation in the fetal and newborn hypothyroid
      (Hyt/Hyt) mouse.
AB  - Thyroid hormones influence fetal and neonatal lung growth and maturation.
      However, the effect of naturally occurring, genetically determined hypo- or
      hyperthyroidism on fetal or neonatal lung maturation has not been examined. In
      the hyt/hyt mouse, primary hypothyroidism, which is characterized by a high serum
      TSH concentration, is transmitted as an autosomal recessive trait. It occurs due
      to a mutational defect in the beta-subunit of the TSH receptor. We studied the
      lung ultrastructure of the fetal [18-d-gestation (term = approximately 19.5 d)]
      and neonatal (< 1-d-old) hyt/hyt mouse. In addition, disaturated
      phosphatidylcholine and total phospholipid contents of newborn hyt/hyt mouse
      lungs were determined. Male and female hyt/hyt mice with a high serum TSH
      concentration were made euthyroid by adding 3,5,3'-triiodothyronine to drinking
      water and then mated. Balb-c mice served as euthyroid controls. Fetal and
      neonatal hyt/hyt mice had a higher serum TSH concentration than the Balb-c
      controls. Fetal hyt/hyt mouse lungs showed a large amount of intracellular
      glycogen and fewer lamellar bodies in epithelial type II cells compared with Balb
      c fetal mouse lungs. The neonatal hyt/hyt mouse also showed signs of lung
      immaturity such as persistent epithelial cell glycogen, few lamellar bodies,
      reduced disaturated phosphatidylcholine content, and absent tubular myelin. We
      conclude that fetal and neonatal lung maturation is delayed in the hyt/hyt mouse
      with primary hypothyroidism.

PMID- 7808837
TI  - Dexamethasone treatment of infants at risk for chronic lung disease: surfactant
      components and inflammatory parameters in airway specimens.
AB  - The mechanisms explaining the beneficial effects of glucocorticoid in ventilator
      dependent preterm infants are not known. In the present randomized trial, we
      evaluated the hypothesis that dexamethasone (DEX) treatment of small, preterm
      infants at risk for chronic lung disease favorably affects the surfactant system.
      Twenty-three ventilator-dependent infants, with a mean +/- SD gestational age of
      26 +/- 2 wk and a mean birth weight of 836 +/- 173 g, received 1 wk of treatment
      with either DEX (dose 0.5 mg/kg/d) or placebo beginning at 2 wk of age. The
      airway specimens were analyzed for surfactant components, surface activity,
      surfactant inhibitors, and inflammatory mediators. The concentrations of these
      parameters in epithelial lining fluid were calculated using the urea method. DEX
      treatment decreased the concentration of nonsedimentable protein in epithelial
      lining fluid within 3 d (p < 0.05). The nonsedimentable fraction of airway
      specimens decreased the surface activity of surfactant as a function of protein
      concentration. At a constant protein concentration, the protein from placebo
      treated infants inhibited the surface activity of human surfactant in vitro more
      than protein from DEX-treated infants (p < 0.05). DEX transiently increased the
      concentration of surfactant protein-A in epithelial lining fluid but had no
      effect on surface activity of the sedimentable surfactant complex or on
      concentrations of phosphatidylcholine, IL-1 beta, lactoferrin, or
      myeloperoxidase. We conclude that the acute beneficial effect of DEX treatment in
      preterm ventilator-dependent infants may in part be mediated through a decrease
      in the concentration of non-sedimentable protein and a decrease in the capacity
      of this protein to inhibit surface activity.

PMID- 7808838
TI  - Developmental effects of endothelin-1 on the pulmonary circulation in sheep.
AB  - Endothelin-1 (ET-1) is a polypeptide that has potent hemodynamic effects on the
      pulmonary circulation. To determine whether there are changes in these effects
      with increasing postnatal age, we investigated the effects of ET-1 (250 ng/kg) at
      rest and during pulmonary hypertension in eight lambs (< 1 wk old) and 11
      juvenile sheep (6-12 mo old). At rest, ET-1 did not change pulmonary arterial
      pressure in lambs, but increased pulmonary arterial pressure by 64.0 +/- 37.5% (p
      < 0.05) in sheep. During pulmonary hypertension, ET-1 produced greater decreases
      in pulmonary arterial pressure in lambs than in sheep (26.6 +/- 3.4% versus 18.7
      +/- 8.3%, p < 0.05). In juvenile sheep, the increase in resting pulmonary
      arterial pressure produced by ET-1 was inhibited by meclofenamic acid, an
      inhibitor of prostaglandin synthesis (40.3 +/- 9.9% versus 2.3 +/- 4.7%, p <
      0.05); during pulmonary hypertension, the decrease in pulmonary arterial pressure
      produced by ET-1 was inhibited by N omega-nitro-L-arginine, an inhibitor of
      endothelium-derived nitric oxide synthesis (21.4 +/- 10.7% versus 8.0 +/- 3.6%, p
      < 0.05) and by glybenclamide, an ATP-dependent potassium-channel blocker (18.8 +/
      8.4% versus 4.0 +/- 4.4%, p < 0.05). The hemodynamic effects of ET-1 on the
      pulmonary circulation are dependent on postnatal age. Pulmonary vasoconstriction
      is mediated by prostaglandin production, and pulmonary vasodilation is mediated,
      in part, by release of endothelium-derived nitric oxide and activation of ATP
      dependent potassium channels.

PMID- 7808839
TI  - Inhaled nitric oxide improves gas exchange and lowers pulmonary vascular
      resistance in severe experimental hyaline membrane disease.
AB  - To determine the effects of inhaled nitric oxide (NO) on pulmonary hemodynamics
      and gas exchange in experimental hyaline membrane disease (HMD), we studied 16
      premature lambs (0.78 term) in two separate protocols. All animals were treated
      with exogenous surfactant before mechanical ventilation. In protocol 1, we
      measured the acute response to brief treatment with inhaled NO (20 ppm, 20 min)
      after 2 h of mechanical ventilation with fraction of inspired oxygen of 1.00 (n =
      5). After 2 h, brief NO treatment lowered pulmonary vascular resistance from 0.26
      +/- 0.05 to 0.16 +/- 0.03 mm Hg.(mL/min)-1 (p < 0.01) and improved gas exchange
      (arterial PO2, 44 +/- 9 mm Hg baseline to 168 +/- 45 mm Hg NO, p < 0.01; arterial
      PCO2 45 +/- 5 mm Hg baseline to 35 +/- 4 mm Hg NO, p < 0.05). In protocol 2, to
      determine whether early and continuous treatment with inhaled NO could sustain
      improvement in gas exchange and pulmonary hemodynamics in severe HMD, we compared
      the physiologic effects of ventilation with high inspired oxygen concentrations
      for 3 h with NO (20 ppm, n = 6) and without NO (controls, n = 5). After 3 h, the
      NO treatment group had sustained reduction in pulmonary vascular resistance (0.10
      +/- 0.01 mm Hg.(mL/min)-1 NO versus 0.25 +/- 0.04 mm Hg.(mL/min)-1 control, p <
      0.05), increased left pulmonary artery blood flow (204 +/- 24 mL/min NO versus
      109 +/- 15 mL/min control, p < 0.05), and increased arterial PO2 (114 +/- 27 mm
      Hg NO versus 36 +/- 11 mm Hg control, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7808840
TI  - Creatine deficiency in the brain: a new, treatable inborn error of metabolism.
AB  - In a patient with extrapyramidal movement disorder and extremely low creatinine
      concentrations in serum and urine, in vivo proton magnetic resonance spectroscopy
      disclosed a generalized depletion of creatinine in the brain. Oral substitution
      of arginine, a substrate for creatine synthesis, resulted in an increase of brain
      guanidinoacetate as the immediate precursor of creatine but did not elevate
      cerebral creatine levels. In contrast, oral substitution of creatine-monohydrate
      led to a significant increase of brain creatine, a decrease of brain
      guanidinoacetate, and a normalization of creatinine in serum and urine.
      Phosphorus magnetic resonance spectroscopy of the brain revealed no detectable
      creatine-phosphate before oral substitution of creatine and a significant
      increase afterward. Partial restoration of cerebral creatine concentrations was
      accompanied by improvement of the patient's neurologic symptoms. This is the
      first report of a patient with complete creatine deficiency in the brain.
      Magnetic resonance spectroscopy during arginine and creatine treatment point to
      an inborn error of creatine biosynthesis at the level of guanidinoacetete
      methyltransferase.

PMID- 7808841
TI  - Preliminary localization of a gene for autosomal dominant hypoparathyroidism to
      chromosome 3q13.
AB  - A large family in which hypoparathyroidism was observed to segregate as an
      autosomal dominant trait in three generations was identified. Mutation in the PTH
      gene was excluded by linkage and single-stranded conformational analysis. The
      hypocalcemic phenotype in this family was mapped by linkage analysis using short,
      tandem-repeat polymorphisms to the region of chromosome 3q13. A maximum lod score
      of 2.71 at theta = 0.0 was observed with marker D3S1303. Positive lod scores were
      observed at theta = 0.0 with markers flanking D3S1303. Multipoint linkage
      analysis gave a lod score of 2.71 for the region flanking D3S1303. Simulation
      using the computer program SLINK showed that a lod score of 2.71 at theta = 0.0
      was the maximum lod score possible given the pedigree structure. The simulation
      also showed that given the structure of the pedigree the probability of observing
      a lod score of 2.71 at theta = 0.0 by chance was 1 in 1000. The data presented
      above provide important preliminary evidence supporting linkage to chromosome
      3q13. This region contains a Ca(2+)-sensing receptor gene that is proposed as a
      key signal transduction element for changes in extracellular Ca2+ concentrations
      in mechanisms of regulation of PTH secretion from parathyroid cells. The mutation
      in this family may activate the Ca(2+)-sensing receptor suppressing PTH secretion
      and lowering the "set point" for serum calcium levels.

PMID- 7808842
TI  - Lack of specific symptomatology in children with acute otitis media.
AB  - Although the symptoms of the acutely ill child are important both in the
      diagnosis and follow-up of acute otitis media (AOM), data about them are quite
      limited. We carried out a prospective survey by collecting information on 354
      consecutive children visiting a pediatrician, otolaryngologist or general
      practitioner because of any kind of acute symptoms to compare symptoms of
      children with acute otitis media with those of children with other acute
      infectious diseases. The symptoms and signs observed at home were recorded by the
      parents before the visit and the findings in the physical examination were
      recorded later by the physician. AOM was diagnosed in 191 patients (54.0%). The
      most important symptoms increasing the likelihood of AOM significantly were ear
      related symptoms, such as earache (relative risk (RR) 5.4; P < 0.001), rubbing of
      the ear (RR 5.0; P < 0.001) and feeling of blocked ear (RR 4.5; P < 0.05).
      However, only 67.7% of children younger than 2 years of age with AOM had any ear
      related symptoms. The children with tympanostomy tubes had earache (47.8%) and
      rubbing of the ear (58.8%) of the same magnitude as did children without tubes.
      Rhinitis increased the likelihood of AOM (RR 2.3; P < 0.001) as did excessive
      crying in children older than 2 years of age (RR 3.0; P < 0.001). Fever, earache
      or excessive crying was present in 90.1% of patients with AOM but also in 72.4%
      of patients without AOM.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7808843
TI  - Long term clinical and virologic outcome of primary hepatitis C virus infection
      in children: a prospective study.
AB  - To investigate the long term natural course of primary hepatitis C virus
      infection in children from the beginning, we prospectively followed up 88
      children at risk because of frequent blood transfusions or of hepatitis C virus
      infection from the mother. Ten of the 88 children contracted primary infection
      during follow-up. In the acute stage of infection acute hepatitis with elevation
      of aminotransferases and a positive IgM antibody was found in both children
      infected during open heart surgery, 3 of the 5 multiply transfused children with
      congenital hemolytic anemia and none of the 3 infants infected by their mothers.
      Four of the 10 children later lost hepatitis C virus RNA, whereas 6 had a chronic
      course. Three of the latter 6 children had abnormal aminotransferase activities
      in the chronic phase. Our study suggests that the very young age of primary
      infection and the underlying status of the host may affect the clinical course of
      hepatitis C virus infection in children.

PMID- 7808844
TI  - Neonatal typhoid fever.
AB  - Typhoid fever occurs in children less than 2 years of age but is thought to be a
      mild, often unrecognized illness. Neonatal typhoid fever is a rare but often life
      threatening illness, uniformly fatal in the preantibiotic era. Vertical
      intrauterine transmission from a typhoid-infected mother is implicated in
      neonatal typhoid fever. Ten cases at a rural African hospital are presented.
      Three patients died with two deaths associated with empiric management
      inappropriate for Salmonella typhi. A second clinical presentation in the neonate
      is asymptomatic persistent excretion. Infants < or = 3 weeks old may also be
      infected from an exogenous source and have severe disease. Where typhoid is
      endemic S. typhi should be considered as a cause of sepsis neonatorum and
      appropriate antibiotics included in empiric therapy.

PMID- 7808845
TI  - The value of urinalysis in differentiating acute pyelonephritis from lower
      urinary tract infection in febrile infants.
AB  - There is an ongoing debate on the best way to screen febrile infants for urinary
      tract infection. We examined the urinanalysis (UA) findings on admission among
      infants less than 16 weeks old, with and without acute pyelonephritis (APN), as
      defined by the dimercaptosuccinic acid (DMSA) renal scan findings, performed
      during a 57-month period. Forty-nine cases with a positive DMSA scan were
      compared with 79 negative study cases. A negative UA for leukocytes (< 5 white
      blood cells/high power field) was found in 4 of 49 (8.1%) cases with APN by DMSA,
      and in 34 of 79 (43%) cases with a negative DMSA (odds ratio 10.88 (95%
      confidence interval, 2.31 to 70.3; P < 0.001)). Three of the 4 infants not
      suspected to have APN by their UA findings would have been admitted for a full
      sepsis workup based on their clinical presentation and/or their laboratory
      findings on admission. We conclude that a fresh UA may be a sufficient screening
      method for the exclusion of APN in infants assessed for fever of no obvious
      origin.

PMID- 7808846
TI  - Increasing prevalence of penicillin-resistant pneumococcal infections in children
      in southern Israel: implications for future immunization policies.
AB  - Although penicillin-resistant pneumococci (PR-PnC) are recognized as an
      increasing problem worldwide, data on the prevalence of these strains among
      pediatric patients are incomplete. The present study was conducted in southern
      Israel (1) to investigate the frequency of PR-PnC in invasive and middle ear
      infections in pediatric patients and (2) to assess the impact of resistance on
      the potential role of the candidate conjugate vaccines in preventing childhood PR
      PnC infections. A total of 120 blood or cerebrospinal fluid isolates from 1987 to
      1993 and 78 ear isolates from 1992 to 1993 were serogrouped and tested for
      susceptibility to antibacterial agents. The prevalence of PR-PnC among invasive
      isolates increased from 16% in the years 1987 to 1991 to 36% in 1992 to 1993 (P =
      0.019). This increase was noted mainly for intermediately resistant strains
      (minimal inhibitory concentration, 0.12 to 1.0 micrograms/ml) whereas the
      prevalence of highly resistant strains was 3 and 2% for the 2 periods,
      respectively. The prevalence of PR-PnC among ear isolates in 1992 to 1993 was
      42%. Resistance to other antimicrobial agents (one or more of the following:
      tetracycline, erythromycin, clindamycin and chloramphenicol) was found in 16 (8%)
      isolates, and multiple resistance (resistance to > or = 3 antibacterial agents)
      was found in 9 (5%) isolates. Sixty-five (99%) of the 66 resistant isolates
      belong to Serogroups 6, 14, 19 and 23. The prevalence of these 4 serogroups rose
      from 37% in 1987 to 1991 to 66% in 1992 to 1993 (P = 0.043). This rise was mainly
      because of Serogroup 23, the prevalence of which rose from 3% in 1987 to 1991 to
      23% in 1992 to 1993 (P < 0.001). Eighty-five percent of all isolates belonging to
      Serogroup 23 were resistant to penicillin. Because Serogroups 6, 14, 19 and 23
      are among the commonest pediatric pneumococcal strains, the newly developed
      conjugate pneumococcal vaccines contain these 4 serogroups. The selection of
      antibiotic-resistant strains has thus led to a change in the spectrum of
      serotypes causing invasive disease and to a situation of potential increase in
      vaccine coverage for the proposed pneumococcal conjugate vaccines.

PMID- 7808847
TI  - Increasing Enterobacter bacteremia in pediatric patients.
AB  - Thirty-two episodes of Enterobacter bacteremia were identified in 30 patients at
      Children's Hospital of Michigan between September, 1989, and November, 1992.
      Fifty-six percent of the episodes were nosocomial. Enterobacter accounted for 14%
      of all nosocomial bacteremias and was the most common Gram-negative organism
      causing such infections. Enterobacter cloacae was the most commonly isolated
      species (72%). Twenty-nine (97%) patients had underlying risk factors for
      infection, including central venous catheters in 22. The susceptibility pattern
      of 46 Enterobacter isolates from blood during the same study period showed high
      resistance to extended spectrum penicillins and third generation cephalosporins
      but low resistance to aminoglycosides and trimethoprim-sulfamethoxazole
      (TMP/SMX). Resistance to third generation cephalosporins increased throughout the
      study period and was higher in patients who had received these agents during the
      previous month. In situations where there is a high frequency of Gram-negative
      bacteremias with organisms resistant to third generation cephalosporins, we
      suggest that initial therapy be a combination of a beta-lactam agent and an
      aminoglycoside or TMP/SMX.

PMID- 7808848
TI  - Safety and immunogenicity of a subunit respiratory syncytial virus vaccine in
      children 24 to 48 months old.
AB  - A subunit vaccine for respiratory syncytial virus (RSV) consisting of purified
      fusion glycoprotein (designated PFP-1) was tested in children 24 to 48 months
      old. Two doses of 20 micrograms (n = 13) and 50 micrograms (n = 10) were compared
      with a saline (n = 24) placebo control group. Local and systemic reactions,
      reported within 96 hours postvaccination, were mild, transient, and did not
      differ significantly from the control cohort. Long term follow-up through at
      least one, and in some cases two, RSV seasons showed no serious RSV illness in
      vaccinees at any time. There was, therefore, no evidence of disease enhancement
      postvaccination. In the 20-micrograms cohort, 92% responded to vaccination by a 4
      fold increase in enzyme-linked immunosorbent titer to the F glycoprotein and 42%
      had a 4-fold or greater rise in neutralizing titer to the A2 virus. In the 50
      micrograms cohort 100% responded by enzyme-linked immunosorbent to the F
      glycoprotein and 70% responded by A2-neutralizing titers. The neutralizing titers
      in the vaccinated cohorts were similar to those seen previously in adults. These
      data show the ability of the subunit vaccine to boost existing immunity and to
      prime for a response to natural virus exposure in children who were seronegative
      at the time of vaccination.

PMID- 7808849
TI  - Growth and joint symptoms in children treated with nalidixic acid.
AB  - To analyze the effects of quinolones on growth and joints in children we
      identified 78 patients who had been receiving nalidixic acid for 116 days on the
      average (range, 3 to 570 days) from a random sample of 3094 of 16,409 children
      treated with long term medication because of recurrent urinary tract infection.
      Two controls per each index case, matched for sex and the age at which the first
      medication for recurrent urinary tract infection occurred, were chosen. Frequency
      of joint symptoms and examinations or possible treatments for arthropathies were
      similar in the index (n = 44) and control (n = 62) cases. Detailed growth data
      were analyzed from 39 case-control pairs after the mean follow-up time of 19.6
      years (range, 14.8 to 24.7 years), and no growth disturbances were found. The
      final heights (age, > 18 years) of the index and control cases were similar (n =
      31 case-control pairs). We conclude that nalidixic acid does not cause
      arthropathies or hamper growth in children, which supports the suggestion that at
      least short treatment periods with quinolones are safe.

PMID- 7808850
TI  - The Histoplasma capsulatum antigen assay in disseminated histoplasmosis in
      children.
AB  - Progressive disseminated histoplasmosis is often fatal without treatment and
      requires rapid and accurate laboratory diagnosis. Radioimmunoassay for
      Histoplasma capsulatum var. capsulatum antigen has been established as a
      sensitive and accurate diagnostic technique for disseminated histoplasmosis in
      adults; this study examines the radioimmunoassay in children. The clinical and
      laboratory records of 26 patients 18 years old or younger in whom H. capsulatum
      antigen was detected in urine by radioimmunoassay and at least one other positive
      corroborative standard test were evaluated. Twenty-two (85%) had disseminated
      disease, and 4 (15%) had self-limited pulmonary disease. Positive corroborative
      tests included serologic tests in 17 of 22 (77%) patients tested, tissue stains
      in 5 of 9 (56%) and fungal cultures in 16 of 24 (67%). Patients with disseminated
      histoplasmosis had a greater degree of antigenuria than those with self-limited
      infection. In 20 patients with progressive disease treated with amphotericin B,
      antigen levels declined, and the decrease in antigenuria correlated with clinical
      improvement. The radioimmunoassay for H. capsulatum antigen in urine is an
      important test in the diagnosis of disseminated histoplasmosis and is useful for
      assessing the efficacy of treatment. The presence of urinary antigen is strong
      evidence for progressive disease that requires treatment.

PMID- 7808851
TI  - Mechanisms of action of intravenous immune serum globulin therapy.

PMID- 7808852
TI  - Congenital rubella after anticipated maternal immunity: two cases and a review of
      the literature.

PMID- 7808853
TI  - Leuconostoc sepsis in association with continuous enteral feeding: two case
      reports and a review.

PMID- 7808854
TI  - Dexamethasone therapy in meningitis: potentially misleading antiinflammatory
      effects in central nervous system infections.

PMID- 7808855
TI  - Stability of chloroquine in an extemporaneously prepared suspension stored at
      three temperatures.

PMID- 7808856
TI  - Hepatitis B virus transmission between a child and staff member at a day-care
      center.

PMID- 7808857
TI  - Tularemia presenting with splenic nodules.

PMID- 7808858
TI  - Occurrence of herpetic whitlow in a twelve-day-old infant.

PMID- 7808859
TI  - Staphylococcal endocarditis complicating a patent ductus arteriosus.

PMID- 7808860
TI  - Salmonella typhi brain abscess in a six-month-old infant.

PMID- 7808861
TI  - Corynebacterium aquaticum septicemia with acute lymphoblastic leukemia.

PMID- 7808862
TI  - Chronic buttock ulcer in a young girl.

PMID- 7808863
TI  - Utility of anaerobic medium in pediatric blood cultures.

PMID- 7808864
TI  - Cefuroxime axetil oral suspension.

PMID- 7808865
TI  - Amphotericin B and hypertension.

PMID- 7808866
TI  - Cardiac toxicity of intravenous erythromycin lactobionate in preterm infants.

PMID- 7808867
TI  - Value of throat cultures in adolescents taking daily antibiotics for acne.

PMID- 7808868
TI  - Procedural learning and the development and stability of character.
AB  - This manuscript presents a neuropsychological model of the development and
      stability of human character. We define character as those things which people do
      routinely, automatically, and unconsciously--those which make people knowable and
      predictable. According to the model, the substrate of character is comprised of
      one's phenotypically based temperamental predispositions. This substrate is
      modified as a result of experience. Research has indicated the existence of
      multiple, relatively independent memory systems, and we are particularly
      interested in the distinction that has been made between declarative and
      procedural learning. Declarative memory involves recall of information and
      events, while procedural memory involves the learning of skills and other
      processes. In neurologically intact persons, these systems work in concert, yet
      they are relatively independent of one another. This model constrains the concept
      of character in a manner that allows researchers to address several issues,
      including (1) the manner in which character develops over time, (2) the
      mechanisms involved in the stability of character, and (3) the processes likely
      to be associated with character change.

PMID- 7808869
TI  - The Developmental Test of Visual-Motor Integration--3R and teachers' ratings of
      written language.
AB  - For a sample of 73 learning-disabled children, the relationship between scores on
      the Developmental Test of Visual-motor Integration--3rd Revision and teachers'
      ratings of writing skills was investigated. After statistically removing the
      contribution of socioeconomic status, achievement, and intelligence, only
      handwriting was significantly related to scores on Beery's test. Given the
      limited diagnostic information provided by the test, psychologists are urged to
      select other measures in assessing students' writing skills.

PMID- 7808870
TI  - Sequential Optimum Selection: a categorical alternative to discriminant analysis
      for conducting research in assessment.
AB  - Sequential Optimum Selection, SOS, a nonparametric computer-assisted alternative
      to discriminant analysis, was introduced and explicated. SOS is an iterative
      procedure that develops ongoing decision rules for discriminating among groups,
      successively expunging frequency distributions or classes until all cases are
      accounted for. In three illustrative comparisons using clinical assessment data,
      SOS proved competitive with discriminant analysis in terms of over-all hit rates
      for parsimonious extraction of meaningful variables. Further, in one
      demonstration using parametric data, SOS held up better on cross-validation.
      While discriminant analysis will, in most cases, yield better discrimination than
      SOS, the latter does not make parametric assumptions and should therefore be
      considered a viable alternative as an exploratory procedure.

PMID- 7808871
TI  - The Recognition Memory Test in the assessment of memory impairment after
      financially compensable mild head injury: a replication.
AB  - The current investigation replicated the findings from a 1992 study by Millis. 20
      subjects with claimed mild head injury who were seeking financial compensation
      obtained significantly lower scores on both subtests of the Recognition Memory
      Test than did 66 rehabilitation inpatients with documented moderate and severe
      traumatic brain injuries. The direct discriminant function derived by Millis was
      cross-validated on the current sample and yielded an improved over-all correct
      classification rate of 83%, with 85% and 82% of the mild and severe traumatic
      brain-injured subjects classified correctly, respectively. Over-all correct
      classification rate in the original study was 76%.

PMID- 7808872
TI  - Geophysical variables and behavior: LXXVII. Increased geomagnetic activity and
      decreased pleasantness of spontaneous narratives for percipients but not agents.
AB  - A total of 48 adults were tested in 24 separate pairs either during the morning
      (10:00 A.M.) or evening (10:00 P.M.). One member of each pair was instructed to
      record (write) impressions and descriptions of 8 different art pieces (5 min.
      each). At the same time the other member of the pair sat in a comfortable chair
      within an acoustic chamber in another room and wrote an ongoing narrative. The
      evaluation and activity dimensions of the words that composed the narratives were
      scored by the Whissell Dictionary of Affect in Language. The increased global
      geomagnetic activity two days before the experiments was significantly associated
      (rhos about 0.60) with the use of more unpleasant words for people who sat in the
      quiet chamber only. Implications for the hypothesis of affective concordance
      between emotionally bonded human beings and its role in episodes of potentially
      veridical telepathic experiences are discussed.

PMID- 7808873
TI  - Future time perspective and positive health practices in adolescents.
AB  - Samples of 84 middle and 106 late adolescents responded to the Future Time
      Perspective Inventory and the Personal Lifestyle Questionnaire. Statistically
      significant positive but weak correlations (.20-.26) were found between length of
      future time perspective and the practice of positive health behaviors in both
      samples. Subscale analyses of individual health practices in relation to future
      time perspective yielded some statistically significant positive but weak
      correlations for both samples.

PMID- 7808874
TI  - Comparison of related perceptual tests.
AB  - 117 female and 76 male undergraduates were administered the ETS Hidden Figures,
      ETS Gestalt Completion, Harshman Figures, and the SEK Test. Results were
      interpreted as indicating that the two types of perceptual tests (flexibility and
      speed) were not factorially independent as the SEK Test correlations did not load
      upon the same factor as that for the ETS Hidden Figures Test. Men scored higher
      on the Hidden Figures and Harshman Figures but on the Gestalt completion task
      left-handed men and right-handed women scored higher.

PMID- 7808875
TI  - Age differences in characteristics of the attention process of electrodermal
      activity during auditory stimulation.
AB  - Age differences in characteristics of the attention process of electrodermal
      activity during passive and active listening tasks were studied with 43 nursery
      and 49 primary school children and 38 university students. The procedure included
      baseline recording, a passive listening task, instruction, and an active
      listening task. Significant differences in skin conductance response (SCR) were
      found among the three age groups. The SCR became smaller for the groups of
      increasing ages only for the active listening task. As the trials progressed,
      there was a trend in the three age groups for decreasing SCR amplitude during the
      passive listening task.

PMID- 7808876
TI  - Hand differences and reported intensity of nociceptive stimuli.
AB  - The hypothesis tested in the present study was that subjects would report higher
      intensity of heat-pain sensation for the left hand than for the right given right
      brain dominance for negative emotion and tactual sensitivity. Low, medium, and
      high temperatures (42 degrees, 45 degrees, and 48 degrees, respectively) were
      presented to 20 healthy subjects' left and right forearms, wrists, and backs of
      hands. Using a modified magnitude-estimation scale, subjects rated the intensity
      of "heat-discomfort" that they felt following each 5-sec. stimulus presentation.
      Mean magnitude estimations for the left- and right-hand responses to high,
      medium, and low heat were analyzed using a 2 x 3 totally within-subjects analysis
      of variance. No significant differences between the right and left hands were
      observed for intensity of pain perception.

PMID- 7808877
TI  - Sex differences in methods for suicide.
AB  - Men and women did not have different suicide rates by solids or poisons in
      nations of the world in 1980. Men had higher suicide rates by all other methods.

PMID- 7808878
TI  - Measurement of cognitive load in instructional research.
AB  - The results of two of our recent empirical studies were considered to assess the
      usefulness of subjective ratings and cardiovascular measures of mental effort in
      instructional research. Based on its reliability and sensitivity, the subjective
      rating-scale technique met the requirements to be useful in instructional
      research whereas the cardiovascular technique did not. It was concluded that the
      usefulness of both measurement techniques in instructional research needs to be
      investigated further.

PMID- 7808879
TI  - Foot agility and social anxiety in older children (9-15 years).
AB  - According to Paul MacLean's phylogenetic model of the brain, the anterior
      cingulate should be associated with interpersonal emotional bonding. If this
      assumption is correct, then foot agility (primarily affected by the dorsal
      medical surface of the cerebrum) should be associated with attenuated bonding and
      enhanced social anxiety. It would not be associated with finger agility, finger
      agnosia, or toe agnosia because their integrity involves more distal portions of
      the cortex. Strong age-dependent and linear increases in agility but not agnosia
      were shown for the fingers and the feet for normal children (28 girls, 28 boys)
      between 9 and 15 years of age. As predicted, a correlation of -0.50, not
      confounded by age or other measures, was noted between foot agility and social
      anxiety, but was statistically significant for the girls, not for the boys.

PMID- 7808880
TI  - Effect of personality on magnitude-estimation scaling of complex auditory
      stimuli.
AB  - The purpose of the present study was to examine the effect of the personality
      trait of extraversion/introversion on magnitude-estimation scaling of complex
      auditory stimuli. Two groups of subjects, 10 who liked rock music (M age = 22.4
      yr.) and 10 who disliked rock music (M age = 21.9 yr.), were tested. Subjects
      were instructed to assign numerical values to a random series of nine
      suprathreshold intensity levels of a 10-sec. sample of rock music. Each subject
      was given the Eysenck Personality Inventory, a test designed to measure the
      personality trait of extraversion/introversion. Statistical analyses indicated
      that the personality trait of extraversion/introversion did not appear to have an
      effect on the way the subjects scaled the rock-music stimulus.

PMID- 7808881
TI  - Lingual vibrotactile magnitude-estimation scaling using a limited set of
      suprathreshold stimulus intensities.
AB  - The purpose of the present study was to assess feasibility of lingual
      vibrotactile suprathreshold testing with a limited number of intensities. 25
      subjects ranging in age from 18 to 26 years (M = 19 yr.) participated. Two
      magnitude-estimation scaling tasks were presented to each subject with 1 wk.
      between tasks. One magnitude-estimation task involved eight suprathreshold
      intensities and the other involved four. Statistical analyses showed that there
      was no difference in subjects' responses to the two scaling efforts. In pure
      research endeavors it might make sense to continue to obtain as many magnitude
      scaling data points as possible, but practical prudence may dictate a limited set
      of suprathreshold intensities for efficiency and subjects' comfort.

PMID- 7808882
TI  - Test-retest reliability of the Dynavision apparatus.

PMID- 7808884
TI  - A study of cognitive loading in dual-coding theory.
AB  - 15 university students were engaged in a task of recalling sentences with and
      without figures. Analysis of the number recalled indicated that cognitive loading
      for sentences with figures was more effective than for recall of sentences
      without figures.

PMID- 7808885
TI  - Irlen filters and reading strategies: effect of coloured filters on reading
      achievement, specific reading strategies, and perception of ability.
AB  - The effect of tinted nonoptical (Irlen) lenses was investigated with 29 lens
      using subjects and a control group of 31 subjects. Assessment of reading four
      months after the initial screening showed a significant improvement in reading
      rate and comprehension but not in accuracy. A significant decrease in the number
      of pauses while reading was also noted for the lens users as well as increases in
      correlation between word repetition and reading rate and accuracy. The lens users
      also showed significantly improved scores on a scale of attitude towards school
      tasks.

PMID- 7808883
TI  - Microgenetic styles of regulation in schizophrenia.
AB  - Styles of adaptation to the Stroop task were studied with the Serial Color-Word
      Test among 50 schizophrenic patients and 50 sex- and age-matched clinical
      controls. Measures of linear (R) and nonlinear change (V) in reading times were
      derived for each of the five interference trials. Schizophrenia was significantly
      characterized by (1) a high sum of nonlinear change, (2) the Cumulative
      Dissociative pattern (high R and high V), (3) concomitantly high secondary Vs (V
      of the 5 Rs and V of the 5 Vs), and (4) Cumulative-Dissociative secondary
      patterns (gradual increase of both linear and nonlinear change on both the 5 Rs
      and the 5 Vs).

PMID- 7808886
TI  - Monitoring radio programs and time of day affect simulated car-driving
      performance.
AB  - Whether radio monitoring, task difficulty, and time of day affect driving
      performance was examined in a computer-controlled, simulated driving task.
      Driving performance was defined as the absolute deviation of the car position
      from road midline as displayed on the computer monitor. We found for 12 men and 8
      women (i) an expected, marked deterioration of performance with increasing task
      difficulty, (ii) a deterioration of performance in the morning, and (iii) a
      deterioration of performance when subjects concurrently listened to radio
      programs except for the easy task conducted in the morning. The latter is
      supposed to be caused by a reactive increase of effort, which is induced by the
      concurrent radio monitoring and stimulated through a perceived impairment of
      attention.

PMID- 7808887
TI  - Melancholia: a Defense Mechanism Test study.
AB  - The defensive organization of Melancholia was explored with a tachistoscopic
      percept-genetic technique, the Defense Mechanism Test. A sample of 20 women
      inpatients with a DSM-III-R diagnosis of Major Depressive Episode or Major
      Depression, Melancholic Type was contrasted with a matched group of depressed
      outpatients and a matched group of nonclinical subjects. Signs of introaggression
      on the hero, statue-repression, and stereotypy significantly characterized
      melancholic patients. The latter were discriminated from depressed outpatients as
      showing more signs of stereotypy and of discontinuity. Mask-disguise defenses
      were typically endorsed by Bipolar melancholic patients and significantly
      differentiated them from Unipolar melancholic patients. One type of stereotypy
      (regarding wrong age attributes of the central figure) successfully predicted a
      poor response to antidepressive therapy. Relevant modifications of the current
      Defense Mechanism Test coding criteria for stereotypy are proposed.

PMID- 7808888
TI  - On the relationship between handedness and season of birth for men.
AB  - A sample of 8,929 male baseball players and a sample of 2,234 males from the U.S.
      National Health and Nutrition Examination Survey are used to assess the relation
      between handedness and season of birth. The results, when coupled with a further
      examination of the 1991 data of Dellatolas, Curt, and Lellouch, lead to the
      conclusion that those born during the spring and early summer are more likely to
      be left-handed than are those born during the fall and winter.

PMID- 7808889
TI  - Preference for darker faces in photographs at different phases of the menstrual
      cycle: preliminary assessment of evidence for a hormonal relationship.
AB  - Six pairs of photographs showing human faces of both sexes were presented to 98
      women who had to choose the more pleasing one of each pair. Faces within each
      pair were identical except for a slight difference in complexion. For women not
      taking oral contraceptives, skin-color preference differed significantly between
      two groups of subjects classified according to the current phase of their self
      reported menstrual cycle: darker male faces were judged more positively by
      subjects in the phase when the estrogen/progesterone ratio was expected to be
      high than by those in the phase when this ratio was expected to be low. Female
      faces evoked no such cyclic response. Users of oral contraceptives showed no
      cyclic response to either male or female faces. These results suggest a mental
      mechanism whose inputs are (a) hormonal state, (b) visual identification of the
      sex of the face being observed, and (c) visual recognition of complexion, and
      whose output enters into evaluation of male and female faces. Replication with
      direct measures of hormonal state is recommended.

PMID- 7808890
TI  - The Health Professions Stress Inventory: factor structures for pharmacists.
AB  - Scores from a sample of pharmacists on the Health Professions Stress Inventory
      were factor analyzed to identify any underlying components of these
      professionals' job-related stress. Data were collected via mail questionnaires
      from a nationwide sample of 573 practicing pharmacists. Three- and four-factor
      solutions, using both orthogonal and oblique rotations, were compared. Based on
      these comparisons, a four-factor oblique solution was judged to be most
      appropriate, the four factors being labeled Professional Recognition, Patient
      Care Responsibilities, Job Conflicts, and Professional Uncertainty. The factors
      show evidence of internal consistency and construct validity.

PMID- 7808892
TI  - Note on the ontogeny of assimilative illusions: a reply to Pressey (1987).
AB  - It is argued that a previous study showing the parallel lines illusion is
      stronger in adulthood than in adolescence or old age is methodologically sound.
      Further, this finding does not necessitate a defense of assimilation theory based
      on epistemology that links the phenomenal properties of illusions to the
      techniques of measurement. Rather, it is suggested that Pressey's 1974 and 1987
      hypothesis that all illusions of assimilation decline from childhood to adulthood
      mistakenly extends the decrement into adulthood when in fact the decrement occurs
      only between the ages of 6 and 10 years.

PMID- 7808891
TI  - Increasing awareness of sleep hygiene in rotating shift workers: arming law
      enforcement officers against impaired performance.
AB  - Research into the effects of rotating shift work on health, social, and
      performance indices suggests significantly more health concerns and judgement
      errors and poorer sleep patterns in shift workers on rotating versus nonrotating
      schedules. 31 male and 7 female law-enforcement officers voluntarily participated
      in a training session on sleep hygiene practices. On the Sleep Hygiene Awareness
      and Practice Scale administered prior to and after training were significant
      increases in awareness of sleep hygiene and knowledge of nicotine, caffeine, and
      hypnotics. We predicted that use of this knowledge would increase sleep
      satisfaction. However, 1-mo. follow-up scores on the Post-sleep Inventory of
      Webb, et al. reflected no change. It appears that scheduling demands, coupled
      with feelings of low self-efficacy toward managing those demands, resulted in
      little or no practice of sleep hygiene. A more productive approach may be to
      incorporate a comprehensive behavioral program within departments to instill and
      reinforce better practice of sleep hygiene.

PMID- 7808893
TI  - Family reading habits and academic achievement of children from polygynous,
      monogamous, divorced, and nondivorced families.
AB  - This study investigated the relationship between family reading habits and the
      academic achievement of 1021 Xhosa-speaking children whose mean age was 15.3 yr.
      A questionnaire was administered to identify each pupil's family status. Analysis
      of variance indicated positive and statistically significant main effects for the
      two variables on a reading habits score.

PMID- 7808894
TI  - Relations of selected variables and perception of success in volleyball.
AB  - This study examined the relations of selected variables and the perceived success
      of 39 college-age subjects participating in a beginning volleyball class.
      Measures of motor trials, successful motor trials, preclass mood, perceived
      challenge, perceived behavior of the teacher, and perceived success were taken on
      11 separate days during an 8-week class. The mean response for the 11 days was
      used for statistical analysis. Pearson's product-moment correlations indicated
      all predictor variables were significantly related to perceived success. A
      stepwise multiple regression analysis showed that preclass mood was the best
      predictor of perceived success, with perceived challenge, teacher's perceived
      behavior, and successful motor trials also entering the regression equation.

PMID- 7808895
TI  - A thermal perception scale for use during resting exposure to cold air.
AB  - The present investigation introduces a thermal perception scale (TS) for use
      during protracted resting cold exposure. The scale contains categories ranging
      consecutively from 0, i.e., Nothing at all, to 10, i.e., Very, very cold. Eight
      Caucasian men were randomly exposed to ambient air in a climatically controlled
      environmental chamber of 8 degrees, 12 degrees, and 27 degrees C for 120 min. on
      3 separate occasions and monitored for rectal temperature (Tre), mean skin
      temperature (Tsk), ventilation (VE), and oxygen consumption (VO2). The terminal
      perceptual categories were anchored for 8 subjects and a standard set of
      instructions was presented prior to each trial. The anchor temperature was the
      room air in the anteroom which was 27 degrees C, representing 0, i.e., "Nothing
      at all," to extend the scale so that subsequent judgments on the scale were
      expressed in relation to this category. In addition, the subjects were also asked
      to imagine the coldest that they have ever experienced and this was designed to
      anchor "Very, very cold." The relations between scale scores and the
      thermoregulatory variables were examined with a simple linear regression and
      coefficients of correlation and determination for each subject. High coefficients
      of determination between Tsk, VO2, and VE indicated that, for individual
      subjects, the scores on the scale were related to VE, Tsk, and VO2. High
      reliability coefficients for TS were also reported. In addition, the ratings and
      VO2 relation tended to be similar between subjects. Therefore, this scale appears
      to be a valid and reliable tool for measuring the perception of cold when at rest
      in air.

PMID- 7808896
TI  - Characteristics of muscle activities in a quick change in magnitude of force.
AB  - The present study was designed to examine the characteristics of muscle
      activities in a quick voluntary change in magnitude of force. 15 subjects were
      asked to change their magnitude of force from 50% of maximal isometric elbow
      flexion strength (MVS) to 20% MVS as quickly as possible. On each EMG of biceps
      and triceps, a period with no muscle activity was observed. It seems that the
      occurrence of the pause in muscle activity on EMG contributes to more quick
      change in magnitude of exerted force.

PMID- 7808897
TI  - Finger-movement tracking scores in healthy subjects.
AB  - The purpose of this study was to examine the effects of age, sex, and hand
      preference on precise control of voluntary movement at the index finger
      metacarpophalangeal joint in able-bodied volunteers. An electrogoniometer was
      attached to this joint and connected to a computer. The computer screen displayed
      a sine wave target that each subject attempted to track with careful extension
      and flexion finger movements. Accuracy index scores were calculated for the
      extension phases, flexion phases, and the total sine wave. Each subject performed
      three tracking trials and the average for each of the above scores was computed.
      The results showed that younger subjects tracked significantly more accurately
      than older subjects and men tracked significantly more accurately than women.
      Also, the subjects tracking with the nonpreferred hand (15 right, 105 left)
      tracked significantly more accurately than those subjects tracking with the
      preferred hand (112 right, 8 left) in the flexion phases of the test. The data
      from these able-bodied subjects provide a base for comparison of patients' data,
      which may be helpful in the early recognition and monitoring of problems with
      precision in movement control.

PMID- 7808899
TI  - EMG and cardiovascular responses to emotionally provocative photographs and text.
AB  - Previous studies on the psychophysiology of human emotion have repeatedly shown
      general and occasionally specific facial EMG (mu v) and covert cardiovascular
      response relationships to emotionally provocative photographs. Less clear are the
      relationships between psychophysiological response indices measured during the
      silent reading of emotionally charged versus emotionally neutral text. In this
      study, 12 adult subjects were presented two emotionally loaded color and black
      and-white photographs and two brief newspaper articles, one emotionally charged
      and the other emotionally neutral in content. Each independent stimulus was
      presented for 1 min., preceded by a rest according to a multiple baseline
      reversal design. Subjects evaluated each pictorial and textual stimulus condition
      according to adjective dimensions on 7-point rating scales. Mean values for
      corrugator supercilii EMG (mu v), upper trapezius EMG (mu v), surface temperature
      (degrees F), and heart rate (bpm) measured by finger photoplethysmography were
      measured during each rest and test period. Significant increases in the subjects'
      mean corrugator supercilii EMG (mu v) measures were observed during all color and
      black-and-white photograph presentations for both emotional and neutral content.
      As predicted, the subjects' mean corrugator supercilii EMG (mu v) measures
      increased significantly while silently reading text with an obvious unpleasant
      emotional tone. A significant positive relationship was observed between the
      subjects' mean ratings and mean corrugator EMG (mu v) difference values for the
      emotionally loaded color photographs.

PMID- 7808898
TI  - Performance on the Wechsler Intelligence Scale for Children as related to
      salivary testosterone in children with learning disabilities: a poststudy
      analysis.
AB  - Reanalysis of testosterone values published in 1993 gave a significantly higher
      mean and standard deviation for 15 learning-disabled children scoring P > V than
      those for 10 scoring V > P but not for a matched nonlearning-disabled group.
      Replication with larger samples would allow a test of hemispheric integration.

PMID- 7808900
TI  - An alternative measure of the frequency of suicide and homicide and its social
      correlates.

PMID- 7808901
TI  - Perception of Success Questionnaire: preliminary validation in an adolescent
      population.
AB  - The purpose of this study was a preliminary examination of the psychometric
      properties of the Perception of Success Questionnaire among adolescents. The
      questionnaire was developed to assess dispositional achievement goal orientation.
      Responses of 96 adolescents (M = 11.3 yr.) suggest that the questionnaire has a
      stable factor structure and acceptable internal consistency. Analysis assessing
      the discriminative validity of the task and ego subscales suggests a coherent
      relationship between the subjects' goal orientation and their beliefs about
      sport. In contrast to the findings from education, however, where differences in
      individuals' task orientation appear key, present results suggest that
      differences in ego orientation may be important in sport.

PMID- 7808902
TI  - Skin conductance, Marlowe-Crowne defensiveness, and dental anxiety.
AB  - The present study assesses the relationship between self-reported dental anxiety
      (Dental Anxiety Inventory, Dental Anxiety Scale, and Duration of
      Psychophysiological Fear Reactions), electrodermal activity (skin-conductance
      level and frequency of spontaneous responses), and Marlowe-Crowne defensiveness.
      All measurements were made twice. The first session was scheduled immediately
      before a semi-annual dental check-up (stress condition), and baseline
      measurements were made two months later without the prospect of a dental
      appointment. Subjects were male dental patients who regularly attended a
      university dental clinic and a clinic for Special Dental Care. The main findings
      were that the low anxious-high defensive-scoring (Marlowe-Crowne Denial subscale)
      university patients showed significantly higher skin-conductance levels and
      frequency of nonspecific fluctuations than the low anxious-low defensive-scoring
      subjects. Besides, the conductance values of the low anxious-high defensive
      scoring subjects resembled those of the high anxious-low defensive-scoring
      patients of the clinic for Special Dental Care, the baseline frequency of
      nonspecific fluctuations excepted.

PMID- 7808903
TI  - Mental rehearsal in table tennis performance.
AB  - Effects of mental rehearsal were assessed on two measures of table tennis
      performance, counterattack forehand and counterattack backhand. Mental rehearsal
      combined with observational and physical techniques (N = 40) appeared to improve
      table tennis performance both qualitatively and quantitatively. Correlations
      suggested mental training effects cannot be explained only in terms of visual
      imagery.

PMID- 7808904
TI  - Correlates of accuracy in judging genuine versus simulated suicide notes.

PMID- 7808905
TI  - Suicide in wide-open spaces.

PMID- 7808906
TI  - Attention-deficit hyperactivity disorder: alternatives for psychotherapy?

PMID- 7808907
TI  - Psychometric equivalence of the Hasegawa Dementia Scale-Revised with the Mini
      Mental State Examination in stroke patients.
AB  - Responses to the Hasegawa Dementia Scale-Revised and the Mini-Mental State
      Examination were examined for 49 stroke patients to investigate the psychometric
      equivalence between the two tests. Pearson product-moment correlation and
      Spearman rank-order correlation between the two tests were 0.87 and 0.78. Each
      test's scores significantly correlated with the Full Scale IQs on the Wechsler
      Adult Intelligence Scale--Revised: 0.61 for Hasegawa's Dementia Scale and 0.69
      for the Mini-Mental State Examination. These values indicate that the two tests
      are judged comparable measures for screening cognitive impairment in stroke
      patients.

PMID- 7808908
TI  - Ball color, eye color, and a reactive motor skill.
AB  - Researchers investigating performance differences between light- and dark-eyed
      individuals have indicated that dark-eyed individuals perform better on reactive
      activities than light-eyed individuals. College students (61 men, 64 women)
      performed a forehand rally with different colored racquetballs. Eye color, sex,
      and total hits were recorded for each subject. Men scored significantly better
      with balls of each color than did women. Dark-eyed men performed better than
      other subjects and performance was better with blue balls than yellow or green
      balls.

PMID- 7808909
TI  - Examining the time course of prime effects on Stroop processing.
AB  - This study was conducted to assess the effect of priming on the Stroop task over
      time. Color-congruent, color-incongruent, and neutral stimuli were randomly
      presented. Five prime conditions were also used. The prime conditions included
      valid color, invalid color, valid word, and invalid word primes and no prime.
      Primes were presented to 8 subjects at varying stimulus onset asynchronies
      ranging from -200 msec., i.e., 200 msec, before the color-word stimulus, to 200
      msec, i.e., 200 msec, after the color-word stimulus. Analysis suggested the
      facilitory or inhibitory effects of semantic information on the Stroop task are
      reduced when the prime follows the color-word stimulus by 200 msec. This implies
      200 msec. are needed to make the proper color response. A model is proposed to
      account for the findings. Methodological considerations for studies using priming
      and the Stroop task are also discussed.

PMID- 7808910
TI  - Styles of interpersonal contact and muscular tone at rest of some muscles of the
      shoulder.
AB  - Styles of interpersonal contact are related, we hypothesized, to particular
      postural attitude showing the tendency to interact with or to avoid the
      environment. Those attitudes are expressed through myographic patterns. Now we
      examined the interpersonal contact styles and the muscular activity at rest
      (frequency and amplitude) of some muscles of the shoulders of 54 undergraduate
      women in psychology. All subjects declared they were right-handed. Increased
      myographic frequency seems associated with the perception of some levels of
      interpersonal barrier while increased amplitude seems to facilitate contact with
      other persons.

PMID- 7808911
TI  - Influence of age, sex, balance, and sport participation on development of kicking
      by children in grades K-8.
AB  - The purpose of this study was to examine the contributions of age, sex, balance,
      and sport participation on development of kicking by children in Grades K-8. The
      subjects were 379 boys and 337 girls (ages 4 to 14) enrolled in a medium-sized
      school system in southeastern Maine. Each subject was individually assessed on
      kicking development and static and dynamic balance. All subjects completed a
      survey on their participation in school or community-sponsored soccer. To assess
      the independent effects of age, sex, static balance, dynamic balance, and sport
      participation within each grade, data were subjected to multiple regression
      analysis. Development of mature form was significantly related to sex (Grade 6:
      boys outperformed girls), static and dynamic balance (Grade 7), and age (Grade
      6).

PMID- 7808913
TI  - Lateralized visual-field inattention in schizophrenia.
AB  - Numerous studies have shown impaired verbal functioning in schizophrenic patients
      as compared with normals. The verbal deficits are generally attributed to damage
      of the left cerebral hemisphere. This attribution is based on literature which
      suggests that verbal processing is primarily mediated by the left hemisphere in
      right-handed humans. This study explored left-hemispheric integrity directly by
      assessing sustained attention in both the left and right hemispheres of 40
      schizophrenic patients with the Weintraub Cancellation Tasks. Patients made
      significantly more errors of omission on the right visual field than on the left.
      These results are consistent with cognitive research in schizophrenia by
      demonstrating selective left-hemispheric impairment relative to right-hemispheric
      functioning.

PMID- 7808912
TI  - Suicide by region of birth and region of residence.

PMID- 7808914
TI  - Exploring career management for nurses (the what, how, and why).

PMID- 7808915
TI  - Assessing the options.

PMID- 7808916
TI  - Knowing trends.

PMID- 7808917
TI  - Choosing your career goal and making plans.

PMID- 7808918
TI  - Influencing others and using resources.

PMID- 7808919
TI  - Enriching self and revitalizing career.

PMID- 7808920
TI  - Nurses' portraits.

PMID- 7808921
TI  - Gathering information.

PMID- 7808922
TI  - Assessing yourself.

PMID- 7808923
TI  - Teaching and learning at a distance: a review of the nursing literature.

PMID- 7808924
TI  - Retention of nursing students: intervention strategies.

PMID- 7808925
TI  - Caring: curricular issues.

PMID- 7808926
TI  - Doctoral education in nursing: a comprehensive review of the research and
      theoretical literature.

PMID- 7808927
TI  - Empathy: theory, research, and nursing applications.

PMID- 7808928
TI  - [Andrzej Manitius].

PMID- 7808930
TI  - [Effect of treatment with erythropoietin (r-EPO) on hemodynamics of the
      cardiovascular system in patients with chronic renal failure (c.r.f.)].
AB  - Patients with chronic renal failure (c.r.f.) are at high risks of death from
      cardiovascular diseases. It was found that successful treatment of anemia could
      positively influence not only patients well being but also caused some
      unfavourable hemodynamic changes. The aim of the study was the estimation of some
      morphological and functional parameters of left ventricle (lv) in dialyzed and
      predialyzed patients treated with r-Epo. Two groups of patients with c.r.f. were
      studied. The I group of 10 dialyzed patients (6 W, 4 M, mean age 34 +/- 11,
      weight 55 +/- 9 kg), and the II group of 9 pre-dialyzed patients (6 W, 3 M, mean
      age 50.6 +/- 10, weight 63 +/- 14 kg). r-Epo (Eprex Cilag AG) was administered
      during 6 months s.c. The I group was given initial dose 3 x 2000 u per week (mean
      dose 24-46 u/kg b.w./per week, the II was on 3 x 2000 u per week (mean dose 24-46
      u/kg b.w./per week) subcutaneously. The doses were adjusted by Hb level in order
      to keep it within limits (10-12 g/dl). Hematological parameters were monitored
      once a week by Technicon H1. Morphology and function of the lv were evaluated
      using echocardiographic measurements performed by Irex IIIA system. According to
      prescriptions of ASE the following parameters have been assessed: lv dimension,
      thickness of posterior wall in diastole and systole and thickness of
      interventricular septum in diastole.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7808929
TI  - [Effect of human recombinant erythropoietin (r-EPO) on behavior of iron status
      parameters in patients with chronic renal failure treated with dialysis].
AB  - For proper erythropoietic response to r-Epo iron, folic acid and B12 vitamin are
      needed. Iron deficiency is the most common in uremic patients treated with r-Epo.
      So the aim of presented study was to measure hematological and iron status
      changes. Studies were carried out in 23 anemic, uremic, hemodialysis patients.
      They were divided into two groups, the first HDa--5 people (3W, 2M) aged 23-49
      (mean 34 +/- 12) years and the second HDb 18 patients (11W, 7M) aged 21-56 (mean
      38 +/- 12) years. Mean hemoglobin (HGB) before r-Epo was 6.9 +/- 1.0 g/dl in HDa,
      and 6.7 +/- 1.1 g/dl in HDb. r-Epo in HDa group was given during 12 weeks i.v.
      and afterwards s.c. for other 4 weeks with initial dose 3 x 50 u/kg b.w. (mean
      during 4 months 65 +/- 24 u/kg m.c. 3 times weekly). Patients from HDb group
      received r-Epo during 12 months only s.c. with initial dose 2000 u three times
      per week (mean during 12 months 26 +/- 4 u/kg m.c. 3 times weekly). Dose of r-Epo
      was changed accordingly to HGB concentration to keep it between 10-12 g/dl. Blood
      morphological parameters were monitored weekly using hematological autoanalyser
      Technicon H1, simultaneously an iron status indicators as iron, transferrin and
      ferritin were measured. An increase of HGB concentration, erythrocytes count and
      Ht value was observed in all patients (I-HGB 10.1 +/- 2.9, II-HGB 9.2 +/-
      1.6).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7808931
TI  - [P1 blood group, secretion status and susceptibility to asymptomatic bacteriuria
      in diabetes].
AB  - Blood-group antigens found on uroepithelial cells and in the secretions may
      affect bacterial adherence and thereby the predisposition to urinary tract
      infection. We determined P1, Lewis-blood-group phenotype and secretor status in
      patients with diabetes mellitus: 12 with asymptomatic bacteriuria and 7 without
      its presence. There was no difference between the two groups in the distribution
      of the P1 phenotype. There was also no statistical difference in the distribution
      of the Lewis phenotype and secretor status, although there appeared to be general
      trend of higher number of Le (a+b-) phenotype and non-secretors present in the
      asymptomatic bacteriuria group. Further studies are necessary to determine the
      role of blood groups and secretor status in the pathogenesis and susceptibility
      to urinary tract infection.

PMID- 7808932
TI  - [Dynamics of changes in lipid metabolism during the first year after kidney
      transplantation].
AB  - Dyslipidemia is one of the first metabolic dysfunction observed among patients
      with end stage renal disease. It can also induce acceleration of renal tissue
      damage. Kidney transplantation may cause recovery of some dysfunction in lipid
      metabolism while influencing deterioration of others. The aim of this study was
      to monitor dynamics of basic lipid parameters in the first year after kidney
      transplantation. The sample included 25 patients (9W, 16M), aged 18-59, avg. 36.
      We have measured concentration of the following parameters in blood serum:
      triglycerides (TG), total cholesterol (CH-C) and apolipoprotein B (Apo B).
      Simultaneously, functions of transplanted kidney were tested with use of routine
      methods. The immunosuppressive treatment of patients followed the scheme:
      cyclosporine + prednisolone + azathioprine. The treatment influence on lipid
      disorders was measured by relevant correlation coefficients. The obtained results
      point to the observation that in the first year after kidney transplantation the
      TG concentration gradually decreases, with simultaneous continuous increase of CH
      C concentration, mainly due to LDL concentration increase. No influence of
      immunosuppressive treatment on lipid parameters was observed. However, lipid
      dysfunction, especially TG, correlated with kidney function.

PMID- 7808933
TI  - [Development of dialysis therapy in Poland during the decade 1984-1993].
AB  - Data concerning status of dialysis therapy in Poland during decade 1984-1993 were
      analysed. It was found that: 1. number of dialysis units increased two times (54
      105), 2. number of dialysis stations raised 2.5 times (294-812), 3. number of
      patients treated with maintenance dialysis was increased 3.5 times (962-3783).
      These data showed dynamic development of this method of renal replacement therapy
      in Poland. However, in Poland acceptance rate dto dialysis therapy is still not
      satisfactory (30-35%). The Programme of the Country Committee for the Promotion
      of Nephrology based on the central founding system for the renal replacement
      therapy provides that by the end of 1995 it will be possible to treat 50% of
      patients with chronic uraemia. Continuous development of different methods of
      renal replacement therapy (hemodialysis, continuous ambulatory peritoneal
      dialysis, renal transplantation) is necessary for achieving possibilities
      compared with developed countries.

PMID- 7808934
TI  - [Acquired cysts of the kidney in patients treated with long-term dialysis].
AB  - There are many reports about development of AC in patients on dialysis therapy
      (DT) and about their pathophysiological consequences. The aim of our studies was
      to determine the prevalence of AC in patients treated with hemodialysis in
      dialysis centre in Gdansk. We also tried to asses relationship between the
      presence of AC, age and sex of the patients, the duration of DT and level of
      haemoglobin (Hb), hematocrit (Ht), red blood cells (RBC) and the prevalence of
      hypertension (H). Renal ultrasound scan was performed in 54 patients, among them
      26 (48.5%) had acquired cysts. No correlation was found between presence of cysts
      and age, sex and nature of the underlying renal disease. There was a positive
      correlation between the prevalence of AC and the duration of DT (DT < 1 year-
      36.8/, DT < 3 years--42.8%, DT > 3 years--59%), it did not, however, reach
      statistical significance. Haematological parameters did not differ significantly
      between both groups, AC--patients, however, received more blood transfusions
      (2983 ml/year vs. 2485 ml/year). Similarly, there were no differences in systolic
      and diastolic blood pressures (mean yearly values before and after HD) between
      both groups, but in AC+ group more patients needed intensive treatment with
      hypotensive drugs. Our results indicate that the prevalence of AC increases with
      the duration of DT. The possibility that the presence of AC may influence
      severity of anaemia and hypertension is suggested.

PMID- 7808935
TI  - [Tuberculosis--an increasing risk for patients treated with long-term
      hemodialysis].
AB  - In the recent years an increase in the incidence of tuberculosis (TB) has been
      observed world-wide, including Poland. In the Department of Nephrology of Gdansk
      School of Medicine, an increase in the incidence of TB has been observed among
      patients undergoing maintenance hemodialysis (HD). The aim of this work was to
      analyse the natural history of TB infection in this group of patients. Over the
      last seven years TB was diagnosed in 9 patients (5 female, 4 male) out of 171
      patients on HD (5.2%). Seven of those were diagnosed in the last three years. The
      average age of patients with TB was 47.2 years. In three patients the clinical
      symptoms of TB has appeared during the first year of hemodialysis treatment
      (average 5.6 months), in the rest the mean period of dialysis before the TB
      diagnosis was 60 months. The TB was extrapulmonary (lymph nodes, pericardium and
      bones) in 5 patients. In most cases the clinical symptoms of TB were present,
      however, one patient was asymptomatic. Four cases were confirmed
      microbiologically and/or histopathologically. All patients treated with
      antituberculous drugs showed clinical recovery or cure, however in six patients
      the anti TB treatment was complicated by adverse drug reactions. One patient died
      and TB was diagnosed post mortem. In two patients who had had lymph nodal TB 2
      and 6 years earlier, we now observed pulmonary TB. There were no cases of TB
      among hemodialysis unit staff. CONCLUSIONS: There is a increasing incidence of TB
      in population of HD patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7808936
TI  - [The role of the adrenergic nervous system in control of extrarenal potassium
      disposal in acute renal failure--unclear pathophysiological and clinical
      problem].
AB  - The effect of catecholamines on the regulation of extra-renal potassium
      homeostasis is well known in some pathological conditions such eg. chronic renal
      failure. However, the role of catecholamines on potassium homeostasis in acute
      renal failure has not been established yet. There are only scarce amount
      literature on this issue showing that both clinical and experimental acute renal
      failure plasma catecholamines are elevated. Presumably, acute renal failure
      associated hyperkalemia is ameliorated by raised plasma catecholamine
      concentration.

PMID- 7808937
TI  - [Bone tuberculosis in a hemodialyzed patient--a difficult diagnostic problem].
AB  - Recent observations indicate quite high incidence of tuberculosis (tbc) in
      haemodialysis population. But there are really only few reports of arthritis the
      infection. Mycobacterial process in this location may imitate many other
      pathological states. Our report refers to 45-year-old man with right knee the
      infection and the peri-arthritic tissue, which developed after 8 years of renal
      replacement treatment. No evidence of the was noted before. Chronic pain,
      swelling and instability of the knee led finally to surgical extraction of
      diagnostic material, which contributed to final diagnosis. We consider this
      report to be important because of only few reported cases of the arthritis.
      Additionally unnecessary delay in commencement of treatment may lead to bone
      destruction.

PMID- 7808938
TI  - [Prevention and treatment of osteoporosis].

PMID- 7808939
TI  - [Results of surgical treatment for tennis elbow].
AB  - This paper presented results after operative treatment of tennis elbow in 32
      patients. I have done such types of operations; Froimson (14), Spencer and
      Herndon (8), Bosworth-Boyd (7) and Froimson with elbow joint synovectomy and
      radial head resection (3). In young people best results I obtained after Froimson
      operation. Results of operative treatment of the tennis elbow are dependent on
      systemic disease. The worst results I obtained in rheumatoid arthritis.

PMID- 7808940
TI  - [Analysis of cause of death in the orthopedic-traumatology ward in the period
      from 01.01.1989 to 31.12.1991].

PMID- 7808941
TI  - [Complications after metal plate stabilization of femoral fracture in a female
      patient with contact hypersensitivity to chromium, nickel and cobalt].

PMID- 7808942
TI  - [Pigmented villonodular synovitis of the hip. Case report].
AB  - A 35-year woman suffering from the tumor of the right groin for 5 years was
      diagnosed as a diffuse pigmented villonodular synovitis and tenosynovitis
      following a 7-month follow-up and examinations. Patient was treated with
      irradiation which produced a subjective improvement but no significant objective
      response to the treatment was noted.

PMID- 7808943
TI  - [Ultrasound monitoring of bone lesions in the treatment of Ewing's sarcoma].
AB  - In the paper, a patient suffering from Ewing's sarcoma is presented. She was
      treated with chemo- and radiotherapy. As one of the methods of monitoring of the
      course of treatment and follow-up after finishing it has been ultrasound
      examination. In the ultrasound examination I have observed gradual diminishing of
      the tumor, up to it's complete disappearance. In the bone there have remained
      only two small hyper-echogenic focuses not changing their shape or size. At the
      beginning in Doppler examination a large arterial flow was found in the tumor,
      having low vessel resistance. In the course of treatment systolic velocity
      decreased and vessel resistance increased up to complete disappearance of the
      flow in the visible small hyper-echogenic focuses in the bone.

PMID- 7808944
TI  - [Chronic mandibular dislocation].
AB  - Various forms of malocclusion which deepens upon unilateral or bilateral
      mandibular dislocation are discussed. The emphasis is on diagnostic problems in
      dislocation produced in an unconscious patient, during the general anesthesia,
      epileptic fit, following tooth extraction or in edentulous patient. Author's own
      3 patients with mandibular dislocation lasting between 2 weeks and 2.5 years are
      presented. In these cases etiological factor of malocclusion was erroneously
      diagnosed as Bell's disease or drug-induced extrapyramidal dyskinesis.

PMID- 7808945
TI  - [Immunotherapy in rheumatoid arthritis of joints].
AB  - The etiology of rheumatoid arthritis (RA) is still unknown. Among the pathogenic
      mechanisms being discussed, the antigen recognition seems to be of great
      importance. Probably the "abnormal" interaction between the presented peptide of
      undefined nature with CD4 T-cell, triggers the pathological events.
      Immunosuppressive drugs, affecting antigen presentation, are in common use in the
      treatment of RA. We discuss the effects of alkylating agents, antimetabolites and
      other immunomodulatory procedures on the course of the disease.

PMID- 7808946
TI  - [Discopathy from the view of neurosurgery].

PMID- 7808947
TI  - [Thoracic outlet syndrome].
AB  - The term thoracic outlet syndrome (TOS) defines neuro-vascular disorders produced
      in the upper extremities due to the external compression of the brachial plexus,
      subclavian artery and vein (neurovascular bundle) within the thoracic outlet.
      Thoracic outlet syndrome may be produced by bone malformations, fibromuscular
      anomalies, neck, and shoulder injuries, and postural defects. Clinical symptoms
      of this syndrome are diversified. However, neurological disorders are
      diversified. However, neurological disorders are prevailing. Thoracic outlet
      syndrome is two-fold more frequent in women than in men, especially in the period
      of physiologic descent of the shoulder girdle. Clinical diagnosis is based mainly
      on physical examination. Doppler segmental blood pressure measurements, limb
      oscillography, rheography, X-ray of the neck and brachial girdle, arteriography,
      intravenous digital subtraction angiography, phlebography of the limbs, and nerve
      conduction studies are being used to confirm the diagnosis. Differential
      diagnosis should consider cervical discopathy and carpal tunnel syndrome. The
      treatment is usually conservative by means of physiotherapy. Carefully planned,
      prolonged conservative therapy (for months) produces favourable effects in the
      majority of cases. Patients with severe symptoms of the thoracic outlet syndrome
      should be treated surgically. Surgery is being successful in 80% of cases.

PMID- 7808948
TI  - [Chromosomal disorders in acute human leukemias].

PMID- 7808949
TI  - [Prophylactic replacement therapy of hemophilia].
AB  - Medical care of patients with hemophilia A and B involves regular ambulatory
      check-ups and contemporary replacement therapy. The Institute of Pediatrics in
      Lodz--as other medical centres in several countries--prophylactically treats some
      hemophilic patients, usually once per 7-10 days, with infusions of absent
      coagulation factor. Such treatment was carried out in 10 boys with severe
      hemophilia A and B with marked clinical symptoms. An analysis of health prior to
      and during prophylactic therapy was carried out. Such an analysis has shown that
      such a treatment is beneficial due to the shortening of hospitalization, change
      in the character of hemorrhage and possibility of rehabilitation free from the
      risk of complications.

PMID- 7808950
TI  - [Treatment results of T-cell acute lymphoblastic leukemia therapy in children
      from 1983-1985].
AB  - Preliminary clinical course and the results of treatment of the acute T-cell
      lymphoblastic leukemia in 11 children have been analysed. All children has been
      treated with aggressive, multidrug chemotherapy with modified BFM scheme 79/81.
      In the majority (approximately 80%) of cases baseline high leucocytosis,
      hepatosplenomegaly and/or lymphadenopathy were seen. Mediastinal tumor was
      present in nearly 50% of cases. The first complete remission was achieved in the
      majority of children but complete recovery was noted only in 4 cases (36.4%). In
      the remaining patients therapy has failed due to early recurrence involving bone
      marrow or CNS. All recurrence developed within the first 18 month of the
      treatment. Further studies on new therapy regimens in T-cell acute lymphoblastic
      leukemia in childhood are needed.

PMID- 7808951
TI  - [Erythroid stem (CFU-E) cells and erythropoietin levels in certain hematological
      diseases].
AB  - The aim of this paper is the trial of explanation of anaemia in certain
      immunological disorders. This approach consists measure of the Epo serum level
      and clot culture of bone marrow CFU-E cells. In the plasmocytoma patients
      inversely proportional dependence between number of CFU-E colonies and percentage
      of plasmocytes in bone marrow was observed. In low grade lymphoma patients the
      number of CFU-E colonies in vitro was greater than the standard value. Non
      proportional increase of Epo serum concentration to the level of anaemia in
      patients with acute leukemia was observed.

PMID- 7808952
TI  - [In vitro studies of anemia accompanying a chronic inflammatory processes and
      neoplasms. Effect of cachectin (TNF-alpha) and lymphotoxin (TNF-beta) on human
      erythropoiesis].
AB  - The influence of tumor necrosis factor alpha and beta, on the clonal growth of
      human erythroid progenitors, from different stages of development--early BFU-E,
      late BFU-E, and CFU-E--in vitro cultures was evaluated. In the cultures of human
      bone marrow cells enriched in clonogenic progenitors the inhibitory effect on
      erythroid colony formation, was confirmed. The influence of TNF-alpha was more
      profound in comparison to TNF-beta and also visible at early BFU-E level. We did
      not however, observe the inhibitory effect, of both inflammatory cytokines, on
      granulocyte-monocytic colony formation. These data demonstrated that TNF-alpha
      and beta inhibit selectively the growth of the erythroid progenitors.
      Simultaneously it was found that early erythroid progenitors did not respond, to
      the kit ligand, in the presence of TNF-alpha.

PMID- 7808953
TI  - [Porphyrin fluorescence in plasma of various types of porphyria].
AB  - Fluorescence spectra of plasma porphyrin were measured in 6 patients with the
      acute intermittent porphyria (AIP), 30 patients with variegate porphyria (PV), 2
      patients with hereditary coproporphyria, 2 patients with porphyria cutanea tarda,
      and in 6 patients with erythropoietic protoporphyria (EPP). It was found that the
      excitation and emission wavelengths at which maximum fluorescence is seen may
      help to diagnose and differentiate PV and EPP. In patients with AIP spectrum
      characteristic for porphyria of such a type was noted in all patients during the
      attack of disease and in only 33% of patients in remission. Fluorescence spectrum
      was normal in asymptomatic family members. In variegate porphyria spectrum with a
      characteristic maximum of fluorescence was noted in all patients during an attack
      and remission, and 62% of the asymptomatic family members.

PMID- 7808954
TI  - [Leukemia secondary to the treatment of other malignancies with
      epipodophyllotoxins].

PMID- 7808956
TI  - [Chloroma--a rare symptom of acute leukemia].
AB  - Chloroma is a tumour composed of immature granulocytes localized in
      extramedullary tissues. Chloroma is noted in the course of the acute non
      lymphoblastic leukemia (ANLL), chronic myeloid leukemia (CML), and in
      myelodysplastic syndromes (MDS) during their transformation in the acute
      leukemias. Due to chloroma infrequency, two cases seen at the Department of
      Hematology, Medical Academy in Warsaw are presented. A survey of the actual
      literature is included.

PMID- 7808955
TI  - [Cyclosporin in the treatment of idiopathic aplastic anemia].
AB  - Five patients with aplastic anemia were treated with cyclosporine A. In four
      cases a positive response was noted. In three out of these patients frequency of
      blood transfusions was decreased. Platelet count increased to 50 x 10(9)/L in two
      cases and in one case agranulocytosis disappeared. Synergistic effect of
      cyclosporine A with oxymetholone and prednisone was seen. In one case an
      improvement lasted only for 1 year. Hepatotoxicity being a complication of
      therapy was noted in one patient.

PMID- 7808957
TI  - [Change of immunologic phenotype in an atypical case of prolymphocytic leukemia-
      role of interferon alpha].

PMID- 7808958
TI  - [Acute pancreatitis in children with acute lymphoblastic leukemia treated with L
      asparaginase].
AB  - The treatment of the acute lymphoblastic leukemia in childhood includes frequent
      administration of L-asparaginase by intravenous route. L-asparaginase is an
      enzyme produced by E. coli and Erwinia chrysanthemi strains. Adverse reactions
      produced by L-asparaginase are numerous, and pancreatitis is being the most
      severe. Children with the acute lymphoblastic leukemia were followed up for 2
      years. Hyperglycaemia and glycosuria were noted in 10% of them resulting in L
      asparaginase cessation or replacement by less toxic agents. The acute
      pancreatitis was produced in 8% of the patients, and was treated typically.

PMID- 7808960
TI  - [Thrombocythemia in a patient after bone marrow autotransplantation with the use
      of human recombinant granulocyte-monocyte colony growth factor].

PMID- 7808959
TI  - [A case of coexisting stomach adenocarcinoma and granulomatosis located below the
      diaphragm].
AB  - A case of the adenocarcinoma of the stomach coexisting with malignant
      granulomatosis is being presented. Clinical stage of the latter was defined,
      using also a specimen collected during laparotomy, as 11B below diaphragm.
      Cytostatics (MOPP/ABV hybrid.), started after gastrectomy, enabled complete
      remission within 6 months; no recurrence of the granulomatosis was noted.
      Relationship between these two neoplastic processes has been discussed.

PMID- 7808961
TI  - [Determination of a system for predicting probability of complete remission and
      its persistence in acute leukemias in adults].

PMID- 7808963
TI  - The carotid bodies in cyanotic heart disease.
AB  - The morphological findings of the carotid bodies of two cases with cyanotic heart
      disease are presented. The first case, a 14-year-old girl with atrial and
      ventricular septal defect accompanied with atresia of the tricuspidal valve
      showed a life-long history of pulmonary hypertension and hypoxaemia. The carotid
      bodies were not enlarged, but the diameters of the glomic lobules were increased
      and its margins were sometimes blurred. There was a marked increase of glomic
      tissue within the carotid bodies. The ratio of chief to sustentacular cells
      remained unchanged. The second case, a 59-year-old man with a double inlet left
      ventricle, had a history of pulmonary hypertension and hypoxaemia of more than 23
      years. The carotid bodies as well as the diameters of the glomic lobules were
      much more enlarged than in case one. There was an increase of glomic tissue
      within the carotid bodies, too. The histological examination showed a marked
      increase of sustentacular and Schwann cells. These results show that the findings
      of carotid bodies in cyanotic heart diseases may be different depending on the
      duration of hypoxaemia.

PMID- 7808962
TI  - Gastrointestinal amyloid deposits in old age. Report on 110 consecutive
      autopsical patients and 98 retrospective bioptic specimens.
AB  - The prevalence of gastrointestinal amyloid was determined in 110 consecutive
      autopsy patients aged 85 years and older. Paraffin sections from the esophagus,
      stomach, small intestine, colon and rectum were stained with Congo red and
      inspected in polarized light. Amyloid was found in 38 patients (36%). Four
      patients had generalized amyloidosis and the remaining 34 revealed more localized
      varieties of amyloid. Immunohistochemical classification with a panel of antisera
      directed against five major amyloid fibril proteins displayed at least four
      different types of amyloid. Twenty cases exhibited amyloid of transthyretin
      origin, five cases were of lambda light chain origin and one case was of amyloid
      A-type. Thus far, unclassifiable amyloid deposits were found in 18 cases, 16 of
      which were strictly localized in subserosal veins. This consecutive autopsy
      series was compared with 98 randomly-selected bioptical gastrointestinal tissues
      with amyloid according to distribution pattern, sex, frequency of the various
      types of amyloid and associated diseases.

PMID- 7808964
TI  - Structural changes in placental barrier of smoking mother. A quantitative and
      ultrastructural study.
AB  - Human placental villi from all three trimesters of pregnancy, in 90 non-smoking
      pregnants and 244 cigarette smoking pregnants, were investigated. In smokers, the
      numbers of syncytial knots and cytotrophoblastic cells increased, depending on
      the cigarettes per day, syncytial buds and vasculo-syncytial membranes decreased
      as the pregnancy proceeded. The mean birth weight and placental weight in smokers
      were decreased, depending on the cigarettes per day at the third trimester. The
      ultrastructure of placental villi from smokers were compared with that on non
      smokers. The villi from smokers had abnormalities of the microvilli, focal
      syncytial necrosis, decreased syncytial pinocytotic activity, degenerated
      cytoplasmic organelles. Using a morphometric method, the basement membranes were
      measured throughout pregnancy. The mean thickness of the basement membranes of
      trophoblastic layer and fetal capillary were found to not only increase with the
      maternal smoking during pregnancy but also attain the maximum in the heavy
      smokers by the third trimester of pregnancy. There was increased collagen in the
      villous stroma and shrinkage endothelial changes in fetal capillaries, in smokers
      the deleterious effect of the cigarette smoking on the placental barrier was
      heavy damage. As a result of impairment of placental barrier, the transports
      between mother and fetus were hampered.

PMID- 7808965
TI  - Invasive micropapillary carcinoma of the breast. A new special type of invasive
      mammary carcinoma.
AB  - After reviewing 986 consecutive cases of breast carcinoma from our files, 27
      ductal infiltrating cancers showing micropapillary differentiation in invasive
      areas (MP) were selected. Special immunohistological and ultrastructural
      techniques were used, and their characteristics compared to those of the Not
      Otherwise Specified type of carcinomas (NOS). Diagnostic areas of MP were easily
      identified in H&E sections and were composed of solid or tubular neoplastic cell
      groups inside a spongy background, where they appeared to swim in aqueous or
      mucinous material. Neoplastic cells displayed the reverse polarity typical of the
      papillary phenotype. This was revealed by the detection of acid mucinous rims,
      lineal deposits of EMA substances, and microvilli in a peripheral position, even
      in areas where the micropapillae resembled tubules. Histologically, most MP were
      mixed with N0S, Papillary, or Mucinous patterns, but regardless of the extension
      of their micropapillary diagnostic component, their tumour size, or their WHO
      histological grade, two thirds had extensive lymphatic vessel invasion and all
      the cases presented massive axillary lymph node metastasis. Six of the twelve
      patients followed died within a mean of 22 months. In conclusion, we propose the
      recognition of "Invasive Micropapillary Carcinoma of the Breast" as a new special
      entity with a potentially high degree of aggressiveness.

PMID- 7808966
TI  - Immunohistochemical detection of metallothionein in primary breast carcinomas and
      their axillary lymph node metastases.
AB  - Metallothioneins (MTs) are low-molecular-weight proteins with specific binding
      for group II metal ions. MTs are involved in the detoxification of metals, but
      can also play a role in protection of the cell against certain anticancer agents
      and from damage of irradiation. High expression of MTs in primary breast
      carcinomas has been found to be associated with poorer prognosis. Expression of
      MT (MT) was examined immunohistochemically in 160 breast carcinomas and their
      concomitant lymph node metastases. The immunoreactivity appeared to be
      independent of the length of fixation when the section was microwaved before
      incubation with the primary antibody, a monoclonal antibody E-9. The findings
      were correlated with various histopathological factors, disease-free survival and
      over-all survival. Patients were divided into two groups, those with MT over
      expression (above 10% of positive tumour cells), and those with low MT expression
      (below 10% positive). MT over-expression was found to be correlated with
      postmenopausal status and inversely with positive progesterone receptor status
      (PgR). MT over-expression showed statistically significant correlation with poor
      over-all survival. No differences in survival were seen between pre- and
      postmenopausal patients. PgR was in univariate analysis a poor prognostic
      parameter. In one fourth of the patients, the lymph node metastases showed
      increased MT expression compared with the primary tumour. These patients had a
      poorer, but not statistically significant different survival. MT expression was
      not correlated to chemo- or radiation therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7808967
TI  - Expression of stromelysin 3 and tissue inhibitors of matrix metallo-proteinases,
      TIMP-1 and TIMP-2, in rheumatoid arthritis.
AB  - Rheumatoid hyperplastic synovial lining cells and sublining fibroblasts are known
      to produce, in vivo and in vitro, matrix metallo-proteinases which degrade
      extracellular matrix components of joints. We have studied by
      immunohistochemistry and in situ hybridization the presence of matrix metallo
      proteinase stromelysin 3 and its potential inhibitors TIMP-1 and TIMP-2 in 5
      cases of normal synovia, 5 cases of chronic synovitis and 12 cases of rheumatoid
      arthritis. Few hyperplastic synoviocytes and some sparse fibroblasts have been
      found to produce stromelysin 3 in all rheumatoid arthritis and 2 chronic
      synovitis. Stromelysin 3 seems to have a limited role in the destructive process
      of extracellular matrix. TIMP-1 and TIMP-2 were largely expressed principally in
      hyperplastic synoviocytes and in endothelial cells of all rheumatoid synovitis
      and 2 chronic synovitis. These findings plead for a balance between matrix
      metallo-proteinases and their inhibitors in these inflammatory lesions.

PMID- 7808968
TI  - Pathomorphological and biochemical alterations in Ehlers-Danlos-syndrome type IV.
AB  - We are reporting the morphological and biochemical data of a patient with the
      characteristic features of the Ehlers-Danlos-Syndrome Type IV (Sack-Barabas Type)
      who died acutely after an episode of recurrent ruptures of the bowel with
      subsequent septic peritonitis. Morphologically, the connective tissue of the
      vessel walls, the dermis and the connective tissue of internal organs,
      particularly that of liver and lung, showed a distinct hypoplasia of the
      collagenous scaffold. Collagen fibers were irregularly arranged which was also
      corroborated by ultrastructural examination of the collagen fibrils of the dermis
      and of intervertebral disc material. Immunohistochemically, a loss in the
      staining intensity for collagen III could be observed in all locations. In
      contrast, the localization of collagen I, IV, V and VI appeared normal, although
      with some reduced staining intensity which particularly held true for collagen I
      in the dermis and vessel wall. The biochemical content of collagen III in lung
      and liver tissue was significantly reduced when compared to control tissues.
      Accordingly, in the pool of newly synthesized collagen from skin fibroblasts,
      only minute amounts of collagen III could be found which was normally secreted
      and had a normal electrophoretic migration.

PMID- 7808969
TI  - Diffuse sinusoidal hemangiomatosis of the spleen. A case report with enzyme
      histochemical, immunohistochemical, and electron-microscopic findings.
AB  - Diffuse hemangiomatosis of the spleen is a very rare benign tumor in which the
      whole spleen is permeated by neoplastic blood vessels. It is occasionally
      accompanied by severe disturbances of blood coagulation. The histogenesis of this
      tumor remains obscure. No systematic investigations of the immunophenotype of the
      neoplastic endothelium have been published. We describe a case of isolated benign
      diffuse hemangiomatosis of the spleen in which the enzyme-histochemical and
      immunohistochemical findings suggested an origin in the splenic sinus endothelial
      cells. Some of the tumor endothelial cells reacted with UEA-1, BMA 120,
      antibodies against the von Willebrand factor, CD34, and CD8, an antigen which, in
      man, is expressed only by suppressor/cytotoxic T cells and the endothelial cells
      of the splenic sinuses. Enzyme-histochemical investigations revealed reactivity
      for nonspecific esterase and lack of reactivity for alkaline phosphatase--a
      pattern typical of the sinus endothelial cells. The tumor could be distinguished
      from other tumors/tumor-like lesions of the spleen that exhibit endothelium with
      characteristics typical of the splenic sinuses (peliosis, splenoma, littoral cell
      angioma) on the basis of its histological features. The lack of expression of
      histiocytic antigens by the tumor endothelium is also evidence against a
      diagnosis of littoral cell angioma, which also derives from the sinus
      endothelium. Thus, this tumor could not be identified as any of the recognized
      tumors/tumor-like lesions of the spleen and it is therefore proposed that it
      should be designated diffuse sinusoidal hemangiomatosis.

PMID- 7808970
TI  - Angiotropic B-cell lymphoma with hemophagocytic syndrome.
AB  - A unique autopsy case of angiotropic lymphoma, which is a rare lymphoma
      characterized by the lymphoma cells confined in blood vessels and with a minimal
      involvement of lymph nodes, is presented. The clinical diagnosis was a malignant
      histiocytosis (histiocytic medullary reticulosis), since clinical manifestations
      were muscle weakness of the extremities, pancytopenia, fever and
      hepatosplenonephromegaly, and biopsy exhibited infiltration by histiocytic cells
      showing hemophagocytosis in the liver sinusoids and the bone marrow, the latter
      with myelofibrosis. Postmortem examination revealed lymphoma cell proliferation
      within small blood vessels of the kidneys, perineural tissue of extremities and
      lungs. Lymph nodes were not involved. In the liver, spleen and bone marrow,
      prominent infiltration of benign histiocytic cells with active hemophagocytosis
      was evident but there was no lymphoma cell infiltration. No viral infection,
      including Epstein-Barr (EBV), was demonstrable either serologically or
      immunohistochemically. Autopsy diagnosis was angiotropic lymphoma of B-cell
      origin (immunophenotypically CD 45+, CD 20-related+, CD 45R+, CD 45 RO-, CD 43-,
      CD 57-, CD 30-, CD 68-) accompanied by hemophagocytic syndrome
      clinicopathologically simulating malignant histiocytosis.

PMID- 7808972
TI  - How much is necessary?

PMID- 7808971
TI  - Prenatal ultrastructural diagnosis in the neuronal ceroid-lipofuscinoses.
AB  - The neuronal ceroid-lipofuscinoses (NCL) are autosomal-recessive disorders in
      childhood of unknown enzymatic origin. They can be recognized by the presence of
      abnormal lipopigments identified by electron microscopy. Based on the study of
      circulating lymphocytes, individual clinical subtypes of NCL can be correlated.
      Prenatal diagnosis of NCL with the electron microscope is now feasible for the
      infantile (Finnish) from (INCL) and late-infantile form (LINCL). INCL-specific
      granular lipopigments are present in endothelial cells of biopsied chorion stroma
      vessels of homozygously affected fetuses. In LINCL, disease-typical curvilinear
      bodies can be identified in uncultured amniotic fluid cells. Prenatal
      ultrastructural recognition of juvenile NCL (JNCL) is still controversial as only
      one single case has been reported. Electron microscopic findings can also be
      corroborated by genetic analysis in INCL and JNCL because the defective genes
      have been localized to chromosomes 1 and 16, respectively, but not in LINCL.
      Documentation of the index patients in the family is essential before prenatal
      diagnosis, and post-abortive confirmation of fetal NCL is also desirable.

PMID- 7808973
TI  - Alternaria alternata infection of skin in a 6-year-old boy with aplastic anemia.
AB  - Although Alternaria is a very common soil saprophyte and plant pathogen fungus,
      human infections are rare. A 6-year-old boy with aplastic anemia presented with
      generalized erythematous papules. Skin biopsies revealed granulomas with fungal
      elements and grew Alternaria alternata. The lesions disappeared following 7 weeks
      of antifungal treatment.

PMID- 7808974
TI  - Metastatic intracranial chordoma in a child with massive pulmonary tumor emboli.
AB  - A 27-month-old boy of Hispanic background developed multiple cranial nerve
      palsies, difficulty swallowing, bloody nasal discharge, and irritability.
      Radiographic evaluations showed extensive destruction of the clivus by a large
      tumor that invaded the sphenoid bone, left cavernous sinus, ethmoid sinus, nasal
      cavity, and left orbit. Multiple pulmonary nodules were also noted. The bone
      marrow and spinal fluid showed no evident tumor cells. Transnasal biopsy revealed
      a chordoma. Treatment was initiated with a combination of ifosfamide, mesna, and
      etoposide along with radiation therapy to the cranial tumor. Shifting pulmonary
      densities were noted on serial films. Despite some clinical improvement, the
      child developed rapidly progressive hypoxemia 3 weeks after admission and died.
      Autopsy showed persistent viable tumor in the primary site and massive pulmonary
      arteriolar tumor emboli, infarcts, and widespread lung parenchymal metastases. No
      other sites of tumor involvement were discovered. This is the second child
      reported with intracranial chordoma, pulmonary metastases at diagnosis, and early
      death attributed to pulmonary tumor emboli.

PMID- 7808976
TI  - Morphology of pulmonary extralobar sequestration in neonatal death by hyaline
      membrane disease.
AB  - We present an unusual case of extralobar pulmonary sequestration associated with
      hyaline membrane disease (HMD) that caused the death of a premature baby in the
      first day of life. The sequestered parenchyma was nourished by an aberrant aortic
      vessel. Notable was the presence of typical HMD in all the lung parenchyma
      perfused by the pulmonary artery; the sequestered lung tissue presented a
      dysplastic structure compatible with CCAM. A few similar cases have been found in
      the literature. In all of the reported cases there are morphologic aspects
      characteristic of HMD in the portions normally receiving blood from the pulmonary
      artery. These findings suggest the importance of the blood pulmonary circulation
      in the pathogenesis of HMD, whose exact causes are not fully known.

PMID- 7808975
TI  - Two-year-old boy with Proteus syndrome and fatal pulmonary thromboembolism.
AB  - A 2-year-old boy with a relatively mild form of Proteus syndrome (PS) died
      suddenly during a previously uncomplicated postsurgical convalescence. Autopsy
      demonstrated massive acute pulmonary embolism, which has not been previously
      reported in PS. In addition, clinically occult mesodermal hamartomata,
      predominantly hemolymphangiomata, were found to be widespread in the
      pelvoabdominal viscera, including spleen, appendix, kidneys, adrenal gland,
      liver, and retroperitoneal soft tissues. Such lesions may well be common in PS
      patients but may not be detected by conventional radiographic imaging techniques
      unless they are fairly large.

PMID- 7808977
TI  - Postmortem findings in the Nijmegen breakage syndrome.
AB  - Autopsy findings for two patients with the Nijmegen breakage syndrome (NBS) are
      presented. This syndrome has the same type of immunologic and cytogenetic
      abnormalities as ataxia telangiectasia (AT). In NBS, however, microcephaly is
      found and progressive cerebellar ataxia and oculocutaneous telangiectasia are
      lacking. We demonstrate a clear neuropathologic difference between these two
      syndromes, as the diffuse cortical cerebellar degeneration characteristic of AT
      was absent in NBS. In the thymus the histologic picture was suggestive of simple
      dysplasia. Lymphoid tissues were slightly atrophic but otherwise structurally
      normal. In one of the two presented cases an extranodal diffuse large cell
      malignant non-Hodgkin lymphoma of B cell immunoblastic type was found in
      Waldeyer's ring, in the small and large intestines, and in the brain, whose
      sequelae had caused death. Six of the 19 patients known with certainty to have
      this syndrome have developed lymphoid malignancy, which indicates that these
      patients are prone to develop malignancies.

PMID- 7808978
TI  - Congenital heart disease and urinary tract abnormalities in two siblings with
      DOOR syndrome.
AB  - The acronym DOOR was first used by Cantwell in 1975 to describe a syndrome
      comprising sensorineural deafness, osteodystrophy, onychodystrophy, and mental
      retardation. To date, 16 cases of the syndrome have been documented in the
      literature. We present two sisters who died in early infancy with the clinical
      features of DOOR syndrome, both of whom in addition had cardiac defects and
      urinary tract abnormalities. Both infants had the classical clinical features of
      sensorineural deafness, seizures, hypoplastic nails, finger-like thumbs, and the
      characteristic facies of the syndrome. Autopsy in each case revealed the
      additional findings of a membranous ventricular septal defect and a septum
      secundum atrial septal defect. The first child had left-sided hydronephrosis and
      hydroureter, and the second sibling had bilateral hydronephrosis, hydroureter,
      and dilatation of the bladder. Congenital heart disease and renal abnormalities
      have not to our knowledge been previously described in association with the DOOR
      syndrome.

PMID- 7808979
TI  - Metachronous pulmonary and cerebral inflammatory pseudotumor in a child.
AB  - An 8-year-old boy had a right pneumonectomy performed for a large inflammatory
      pseudotumor. Over the subsequent 8 years he developed multiple similar lesions in
      the meninges and bilateral cerebral hemispheres as well as new growths within the
      ipsilateral pleural cavity and contralateral lung. Metachronous pulmonary and
      intracranial inflammatory pseudotumor has been reported only once. These lesions
      probably represent a multifocal, exaggerated inflammatory response to some as yet
      unidentified stimuli.

PMID- 7808980
TI  - How useful is postmortem examination in sudden infant death syndrome?
AB  - There exists great variability in the literature as to the percentage of cases of
      sudden and unexpected infant death in which definable causes can be identified.
      Review was undertaken of the clinical and family histories, death scene features
      including parental interviews, and pathological and microbiological features of
      361 consecutive cases presenting as sudden and unexpected infant death with
      minimal preceding symptoms and signs to the Adelaide Children's Hospital over a
      10-year period from 1983 to 1992. Three hundred and twenty-nine cases of SIDS
      were identified. Nine cases (2.5%) were attributed to accidental asphyxia based
      partly on death scene examination. This left only 23 cases (6.4%), which were due
      to a variety of other diverse entities including sepsis, volvulus with sepsis,
      congenital cardiac disease, probable metabolic disorders, heat stroke, and
      unclassifiable disorders. This relatively low figure lends support to definitions
      of SIDS that emphasize the importance of death scene investigation and clinical
      history review prior to postmortem examination.

PMID- 7808981
TI  - Assessment of MYCN amplification in neuroblastoma biopsies by differential
      polymerase chain reaction.
AB  - Amplification of the oncogene MYCN is a genetic change frequently observed in
      neuroblastoma and is an indicator of poor prognosis. MYCN copy number is
      currently determined by Southern blot hybridization. This technique takes 2 to 3
      weeks, is labor-intensive, is sensitive to DNA degradation, and requires large
      quantities of DNA. We have evaluated a new, semiquantitative method of estimating
      gene copy number that uses differential polymerase chain reaction (PCR). The
      procedure can be performed in 1 day, is highly reproducible, and requires only
      nanogram quantities of DNA. It employs a semiquantitative, nonisotopic PCR
      technique based on differential competition for PCR substrates. MYCN gene primers
      are amplified together with primers from a single-copy internal control gene.
      Following electrophoretic separation, the ratio of the two PCR products is
      determined visually and by densitometric analysis of ethidium bromide-stained
      agarose gels. This differential ratio is then compared to a series of ratios
      generated from standards of known MYCN gene copy number. We compared the results
      obtained by this differential PCR method with those obtained by conventional
      Southern blotting in 16 cases of primary neuroblastoma. All amplified tumors were
      detected by differential PCR, and no false positives were observed. We confirmed
      that differential PCR is a rapid and reliable alternative to Southern blotting
      for MYCN copy number assessment and is highly suited to the analysis of DNA
      derived from needle biopsies.

PMID- 7808982
TI  - Characterization of a monoclonal antibody recognizing selective epithelial
      elements of Wilms' tumors and fetal kidneys.
AB  - A new antigen was detected using a monoclonal antibody generated against
      malignant blastema from a Wilms' tumor. This antigen showed variable expression
      in malignant blastemal cells but was never detected in normal blastema of fetal
      kidneys irrespective of gestational stage. In a series of 16 Wilms' tumors, the
      most intense and consistent staining was seen in tubule-associated epithelial
      cells. Such tubular staining is not surprising as the putative induction of
      malignant blastema to differentiate into malignant tubules is thought to parallel
      normal tubulogenesis. This antigen was also associated with epithelial cells
      located in a variety of fetal kidney structures. Again, the staining was most
      consistent in tubular epithelia. This monoclonal antibody reactive with a
      blastemal-epithelial-tubular (BET) antigen should be of value in studying the
      induction of epithelial differentiation in the normal and diseased human kidney.

PMID- 7808983
TI  - Characterization of a monoclonal antibody recognizing the blastemal element of
      Wilms' tumors and fetal kidneys.
AB  - A blastema-associated antigen (BLA-1) was detected using a monoclonal antibody
      against malignant blastema from a Wilms' tumor. The localization of BLA-1 was
      investigated in a series of nine Wilms' cases, five fetal, one childhood, and two
      adult kidneys. In this series, BLA-1 antibody consistently stained cell surfaces
      of all Wilms' tumors containing blastemal components. The same staining pattern
      was maintained in tumors grown as heterotransplants in nude mice. The expression
      of BLA-1 antigen was examined in normal blastema of fetal kidneys. BLA-1 was
      immunolocalized to condensed blastemal cells in the nephrogenic zone throughout
      gestation. In addition, kidney samples from a young child or adults contained no
      blastemal cells and therefore showed no blastemal cell surface staining.
      Glomerular mesangial cell staining was demonstrated in kidneys from 12 weeks of
      gestation through adulthood. This staining in developing and mature glomeruli
      implies that mesangial cells may be derived from condensed blastemal cells. The
      finding of a cell surface antigen common to Wilms' blastema, fetal blastema, and
      mesangial cells has not been previously demonstrated.

PMID- 7808984
TI  - EBV-associated Kaposi's sarcoma in a pediatric renal transplant recipient.
AB  - A 7-year-old boy had undergone kidney transplantation for chronic renal failure
      secondary to bilateral renal hypoplasia. He developed acute and chronic rejection
      and received immunosuppressive therapy. A year later he died with EBV-associated
      hemophagocytic syndrome. The main pathologic findings disclosed visceral (lung
      and stomach) and abdominal lymph node involvement of Kaposi's sarcoma and EBV
      positive immunoblasts in several organs. In the lungs and lymph nodes these had
      the features of polymorphous lymphoimmunoblastic lesions. Because of the peculiar
      distribution of Kaposi's sarcoma lesions a pathogenetic hypothesis is proposed
      based on the site of entry of the virus. This case contributes to expanding the
      relationship between Kaposi's sarcoma and kidney transplantation in the pediatric
      population.

PMID- 7808985
TI  - Congenital soft tissue dysplasias: a morphological and biochemical study.
AB  - The term congenital soft tissue dysplasias (CSTDs) regroups some localized
      malformations of covering soft tissues in children, presenting as various
      clinical entities, either recognized as particular syndromes (e.g., Parkes-Weber,
      Klippel-Trenaunay, Proteus) or, most often, appearing less stereotyped (e.g.,
      segmental hypertrophy or gigantism, lymphedema, angiodysplasia, phakomatosis),
      with a common histopathological lesion, the hamartoma. The aim of this paper is
      to report a morphological and biochemical study of the extracellular matrix of
      skin and subcutaneous tissue in children with CSTD. For every patient,
      pathological tissues were compared with contralateral, symmetrical tissues, taken
      as controls. In all CSTDs, pathological samples were characterized by an increase
      in water and total glycosaminoglycan (GAG) content with a decrease in collagen
      content. Other results lead the authors to distinguish two main entities,
      segmental dysplasia (SeD) and neuroectodermal dysplasia (NeD). Elastic fiber
      content was increased in SeD and decreased in NeD. Hyaluronic acid (HA) and
      dermatan sulfate (DS) were increased in NeD, whereas in SeD, HA was decreased
      with an increase in the DS/HA ratio. Cultured fibroblasts from dysplastic skin
      had slower proliferation in vitro than fibroblasts from control skin, whereas
      their biosynthetic activity concerning collagen and GAGs was greater. The
      difference in the composition of extracellular matrix supports the clinical
      classification of CSTDs in two main groups: segmental dysplasia with or without
      gigantism and neuroectodermal dysplasia (in von Recklinghausen's disease and
      nevi).

PMID- 7808986
TI  - Ultrastructural studies in Langerhans cell histiocytosis: a search for evidence
      of viral etiology.
AB  - The ultrastructure of lesional cells in biopsy material from 50 cases of
      Langerhans cell histiocytosis (LCH) was studied for the effects of virus and/or
      cytokines. Viral "footprints," which actually represent ultrastructural signs of
      the effects of cytokines on cells, were found in 76% of the cases. These were
      detected in lesional Langerhans cells, endothelial cells, and lymphocytes and
      consisted of tubuloreticular structures, cylindrical confronting cisternae, and
      curvilinear membranous formations. No virus particles or virus-specific cell
      products were found. These studies suggest that LCH cells are subject to cytokine
      stimulation but provide no evidence to implicate a virus in the disease process.

PMID- 7808987
TI  - [Sarcoidosis of the heart].

PMID- 7808990
TI  - [Measuring lung volume in the infant--problems with the nitrogen washout method].
AB  - The open-circuit nitrogen washout technique, as developed by Gerhardt et al.,
      seems to be ideally suited for assessing functional residual capacity (FRC) in
      infants. By performing this measurement in over 250 infants throughout the last
      three years, we gathered considerable practical experience of our own, but also
      encountered several methodological problems, which, so far, have received only
      little attention by the relevant literature, or have remained unresolved
      altogether. Our data illustrate the importance of reproducing the infant's own
      breathing rate and tidal volume when calibrating the system. The choice of the O2
      background-flow should be based on the individual peak tidal inspiratory flow, as
      derived from the tidal flow-volume loop. The importance of maintaining this O2
      background-flow unchanged between calibration and measurement is also
      demonstrated. The question, at which N2-concentration the measurement should be
      terminated, has remained unresolved. Diffusion of N2 from blood and tissue into
      the alveolar space is responsible for considerable noise. Our own measurements
      resulted in widely differing FRC-values for different N2-target-concentrations;
      these differences seem to increase with more severe bronchial obstruction.
      Finally, there remains the question, how long the minimal interval between two
      subsequent measurements should be. In conclusion, these unresolved questions have
      to be answered in relevant prospective studies, before recommending this
      technique for routine clinical application.

PMID- 7808988
TI  - [Nocturnal nasal mask ventilation in childhood].
AB  - Nasal intermittent positive pressure ventilation in childhood is a major advance
      in the noninvasive treatment of chronic respiratory failure in childhood. Between
      1987 and 1994 author could found reports about 58 patients aged 2 to 18 years.
      Diagnosis were neuromuscular diseases (n = 51), scoliosis (n = 4), cystic
      fibrosis (n = 2) and central hypoventilation syndrome (n = 1). Author reports
      about indications, physiological effects, advantages, side effects and limits,
      about ethical considerations, technical and psychological preparation and
      realization of intermittent nasal ventilation in childhood.

PMID- 7808989
TI  - [Change in right ventricular diastolic function in children and adolescents with
      mucoviscidosis--a Doppler echocardiographic study].
AB  - The present study investigated the right ventricular filling pattern with
      Dopplerechocardiography in childhood and adolescent patients (n = 31) with cystic
      fibrosis and in normal subjects. The results show that, as the pulmonary pressure
      increases (RPEP/AT > or = 1.0), the peak flow velocity during atrial contraction
      and the triangle under the atrial velocity are significantly increased while the
      acceleration half-time is significantly decreased. These are sensitive parameters
      for right ventricular diastolic dysfunction.

PMID- 7808991
TI  - [Compliance and tolerance of new antitubercular short-term chemopreventive
      regimens in childhood--a pilot project].
AB  - Efficacy of preventive chemotherapy in tuberculosis-infected children depends to
      a great extend on medical compliance and drug tolerability. Two new short-course
      chemoprevention-regimes of tuberculosis--four months Rifampin (A) and two months
      Rifampin plus Pyrazinamide (B)--were compared with the well established regimen
      of six months Isoniacid (C). 150 children (mean age 3.6 years with Tb conversion)
      were randomly allocated to these three regimens. 13 patients were non-compliant,
      in terms of interview, urinary INH-test strips, urine colour and prescription
      frequency: 7 in group C and 3 in group A and B, respectively. Adverse effects
      were observed in 5 patients: 3 in group C and 1 in group A and B. 1 child (group
      B) developed tuberculosis two years after stopping short course chemoprevention.
      Good compliance (94%) as well as neglectable risks of adverse effects (2%)
      justify further controlled studies to evaluate the efficacy of short course
      chemoprevention in childhood.

PMID- 7808992
TI  - [Treatment of acute pulmonary infection in a mucoviscidosis patient with
      extracorporeal lung support].
AB  - This is a report on a mucoviscidosis patient of 30 years of age suffering from
      refractory acute failure of pulmonary function during acute exacerbation of an
      infection with Pseudomonas aeruginosa. To avoid further barotraumatisation of the
      lungs due to continually increasing artificial respiratory pressure, and to set
      the lung at rest until subsidence of a concomitant severe bronchial obstruction,
      we performed modified extracorporal lung assist (ELA). The gas exchange improved
      rapidly with the help of relevant accompanying measures (including negative
      liquid balance, administration of antibiotics, etc.) and the pulmonary infection
      also subsided to a major extent. 26 days after the end of the bypass the patient
      could be transferred for lung transplantation.

PMID- 7808993
TI  - Contractions of the filariid Acanthocheilonema viteae induced by potassium
      chloride.
AB  - The effects of K+ on muscle contractility were explored in the filarial nematode
      Acanthocheilonema viteae (Dipetalonema viteae). The parasite was slit open
      longitudinally and mounted in a smooth muscle chamber that was filled with
      aerated (95% N2-5% CO2) physiological solution at 37 degrees C. KCl at
      concentrations ranging from 20 to 100 mM induced a rapid isotonic contraction of
      the filarial muscle. The maximal response from KCl was similar to the maximal
      response to acetylcholine chloride (ACh). When KCl was applied for several
      minutes, tolerance frequently occurred. Contractions were also induced by K2SO4
      but not by NaCl, Na2SO4 or sucrose. Nifedipine was more than 10 times as potent
      in reducing the KCl-induced contraction as in reducing that caused by ACh. The
      KCl-induced contraction was abolished in a Ca-free physiological medium
      containing ethyleneglycol-bis-(beta-aminoethyl ether) N, N, N', N'-tetraacetic
      acid (EGTA, 10(-4) M). Low [Ca2+]/[Mg2+] solutions blocked the spontaneous
      activity, the KCl-induced contractions, and the ACh-induced contractions. KCl
      also induced contractions in denervated muscle strips, supporting the hypothesis
      that K+ acts directly on the muscle cells. These results indicate that K+ can
      depolarize the muscle membrane and induce a muscle contraction that is dependent
      on extracellular calcium ions.

PMID- 7808995
TI  - Distribution of catecholamine(s) in the nervous system of a mermithid nematode,
      Romanomermis culicivorax.
AB  - The nervous system of the mermithid nematode Romanomermis culicivorax was
      investigated at different developmental stages for the distribution of
      catecholamine(s). The catecholaminergic nervous system increased in complexity
      during development. In the adult nematode, catecholamine(s) occurred in the nerve
      ring and associated ganglia, cephalic nerves, ventral and dorsal nerve cords and
      mid-body region ganglia. The distribution of catecholaminergic ganglia in the
      tail region was different for each sex. The tail region of males contained 16-20
      catecholaminergic ganglia, whereas the tail of females contained only 2 ganglia.
      The catecholamine widely distributed throughout the nervous system of R.
      culicivorax is not dopamine, since immunoreactivity to dopamine was observed only
      in the amphids. The results suggest that the catecholamine(s) is widely
      distributed within the nervous system of R. culicivorax and might function as a
      neurohormone or neurotransmitter in controlling physiological and developmental
      processes.

PMID- 7808994
TI  - Ultrastructure studies on the papillae and the nonciliated sensory receptors of
      adult Spirometra erinacei (Cestoda, Pseudophyllidea).
AB  - The small numerous papillae on the ventral surface of the gravid proglottid of
      adult Spirometra erinacei were studied by scanning electron microscopy. The
      arrangement of clumps of papillae was recognized on the surface of the central
      portion around the genital atrium, with lateral clumps being located above a pair
      of longitudinal nerve cords and marginal ones, on both sides of the proglottid.
      By transmission electron microscopy, two types of nonciliated sensory receptors
      were observed within the papillae. The type I, single receptor was embedded
      within a papilla. This dome-like sensory receptor contained two electron-dense
      collars and four rootlets surrounded by numerous thin filaments. The type II
      receptor was found arranged in groups in the area between the papillae, and the
      apical end was exposed to the external environment. This simple, club-like
      sensory receptor contained electron-lucent vesicles and microtubules. We believe
      that the papillae play an important role in cross-insemination.

PMID- 7808996
TI  - Distribution of FMRF-amide-like peptide in the nervous system of a mermithid
      nematode, Romanomermis culicivorax.
AB  - The nervous system of the mermithid nematode Romanomermis culicivorax was
      investigated at different developmental stages for the distribution of the
      neuropeptide FMRF-amide. An FMRF-amide-like peptide was detected by an indirect
      immunofluorescence technique. The peptidergic nervous system increased in
      complexity during development. In adults, FMRF-amide-like peptide was present in
      the nerve ring, cephalic papillary ganglia, cephalic nerves, amphids, ganglia
      posterior to the nerve ring, longitudinal nerve cords and several mid-body region
      ganglia. The distribution of peptidergic ganglia in the tail region was different
      for each sex. Four clusters of ganglia were present in the tail of females,
      whereas such ganglia were absent in the tail of males. The results suggest that
      FMRF-amide-like peptide is widely distributed within the nervous system of R.
      culicivorax and might function as a neurohormone or neurotransmitter in
      controlling physiological and developmental processes.

PMID- 7808997
TI  - Intra- and interspecific polymorphisms of Leishmania donovani and L. tropica
      minicircle DNA.
AB  - A pair of degenerate polymerase chain reaction (PCR) primers (LEI-1, TCG GAT
      CC[C,T] [G,C]TG GGT AGG GGC GT; LEI-2, ACG GAT CC[G,C] [G,C][A,C]C TAT [A,T]TT
      ACA CC) defining a 0.15-kb segment of Leishmania minicircle DNA was constructed.
      These primers amplified not only inter- but also intraspecifically polymorphic
      sequences. Individual sequences revealed a higher intraspecific than
      interspecific divergence. It is concluded that individual sequences are of
      limited relevance for species determination. In contrast, when a data base of 19
      different sequences was analyzed in a dendrographic plot, an accurate species
      differentiation was feasible.

PMID- 7808998
TI  - Characterization of multiple unique cDNAs encoding the major surface glycoprotein
      of rat-derived Pneumocystis carinii.
AB  - The major surface glycoprotein (MSG) of rat-derived Pneumocystis carinii
      represents a group of related molecules that are encoded by multiple genes. We
      isolated seven unique MSG cDNAs from a library prepared from a single infected
      rat lung. The cDNAs displayed both conserved and variant regions to previously
      described cDNAs. These clones contained inserts that ranged in size from 0.4 to
      1.8 kb and all contained a poly(A) tail. The largest clone, Pc1410, hybridized to
      all 15 chromosomes resolved by pulsed-field gel electrophoresis (PFGE). Protein
      produced by in vitro translation from Pc1410 was immunoprecipitated with affinity
      purified MSG antibodies. The clones were characterized by DNA sequencing of their
      3' and 5' ends. Analysis of the untranslated and coding regions demonstrated that
      the clones contained unique and conserved regions of sequence, but none of the
      clones were identical. Isolation of seven additional unique clones picked from a
      single screening of a cDNA library suggests that numerous MSG transcripts exist
      within a population of P. carinii.

PMID- 7808999
TI  - A morphological study of chronic cerebral toxoplasmosis in mice: comparison of
      four different strains of Toxoplasma gondii.
AB  - The pathological changes, host-parasite relationship and structure of the tissue
      cysts in the brains of mice chronically infected with four different strains of
      Toxoplasma gondii were examined by light and electron microscopy. In mice
      infected with the mouse-adapted ME49 strain for 4, 8, 12, 16 and 25 weeks, the
      pathological changes consisted of moderate to severe meningitis and cuffing of
      blood vessels by inflammatory cells. At 4 weeks post-infection (p.i.),
      lymphocytes were the major cell type, but at later time points, plasma cells
      predominated. Large numbers of cysts were observed at between 4 and 12 weeks
      p.i., with a decrease being seen at 16 weeks p.i. Microglial nodules, many
      containing tachyzoites or bradyzoites, were present at all time points. In
      contrast, the three strains isolated from patients with the acquired immune
      deficiency syndrome (AIDS) resulted in no meningitis in two cases (DEY, DAG) and
      in mild meningitis in one case (WIL), although all three showed some cuffing of
      blood vessels. In addition, only very low numbers of cysts and nodules were
      observed. Ultrastructurally, the cysts of all four strains were seen to be
      located within host cells. The cysts of the ME49 strain differed from those of
      the other strains in that a proportion contained immature and dividing
      bradyzoites at all time points, whereas those of the other strains contained only
      mature bradyzoites. From the observation of nodules with parasites and cysts with
      immature zoites, it would appear that the ME49 strain may result in an unstable
      chronic infection with a continuous turnover of cysts, a feature that should be
      taken into consideration when this strain is used as an experimental model of
      chronic toxoplasmosis.

PMID- 7809000
TI  - Leucine aminopeptidase activity in adults of Pomphorhynchus laevis
      (Acanthocephala): a histochemical study.
AB  - In frozen sections of the acanthocephalan Pomphorhynchus laevis, which is a
      frequent intestinal parasite of cyprinid and salmonid fishes, leucine
      aminopeptidase (APase) was localized histochemically in outer parts of the
      presomal bulbus as well as in all layers and most nuclei of the metasomal body
      wall. Enzyme activity visualized at pH 6.5 using L-leucyl-4-methoxy-2
      naphtylamide as the substrate was also associated with ovarian balls, immature
      larvae, and the testes. The results are discussed with respect to the possible
      function of APases and the proposed sites of amino acid uptake in tissues of P.
      laevis.

PMID- 7809001
TI  - Electron microscopy of surface structures of Blastocystis sp. from different
      hosts.
AB  - Samples of Blastocystis sp. obtained from humans, monkeys, pigs and chickens were
      examined by scanning electron microscopy and transmission electron microscopy to
      compare surface structures. The surface coat of Blastocystis sp. cells from each
      host species showed some morphological variations, but these were not
      sufficiently different to allow judgement to be made on speciation. The surface
      structure morphology appeared similar for samples of Blastocystis sp. from the
      same host species. The surface coat of the cultured human isolate of B. hominis
      was much thinner than that of cells from fresh human faecal material, and the
      cell surface appeared to be smoother and without the small projections seen in
      the fresh forms. Bacteria were frequently found in association with the surface
      coat of Blastocystis sp. from all fresh faecal material. Possible functions of
      the surface coat, especially in relation to protection against osmotic shock, are
      discussed.

PMID- 7809002
TI  - Detection of trypanosomatid Phytomonas parasitic in plants by polymerase chain
      reaction amplification of small subunit ribosomal DNA.
AB  - To improve the diagnosis of Phytomonas infections in plants, we developed a
      polymerase chain reaction (PCR) assay using synthetic oligonucleotides
      complementary to conserved sequences of the 18S small subunit ribosomal (SSU)
      gene. From 10 ng upward of DNA of cultures of Phytomonas isolated from plants,
      fruits, and insects, PCR amplified an 800-bp DNA band that, after restriction
      analysis and probe hybridization, proved to be of 18S rDNA Phytomonas origin. PCR
      was also done with sap samples of tomatoes experimentally infected with
      Phytomonas, yielding amplified 800-bp ribosomal DNA bands before any flagellate
      could be detected by microscopic examination of the fruit sap.

PMID- 7809003
TI  - The reservosomes of epimastigote forms of Trypanosoma cruzi: occurrence during in
      vitro cultivation.
AB  - Reservosomes are large membrane-bound structures found mainly at the posterior
      end of epimastigote forms of Trypanosoma cruzi, the agent of Chagas' disease. We
      screened 5-day-old culture forms of the following strains at the ultrastructural
      level for the presence of reservosomes: T. cruzi strains Y and YuYu as well as
      Trypanosoma (Schizotrypanum) spp. strains M431, M504, and M519 isolated from bats
      (Epitesicus sp.) in Santa Catarina, Brazil. The organelles could be found in all
      strains analyzed, supporting a previous hypothesis that they are a marker of
      trypanosomes of the Schizotrypanum subgenus. Stereological analysis was carried
      out with the Y strain to follow the development of reservosomes and lipid
      droplets during in vitro cultivation of the parasites. Reservosomes were
      partitioned to the daughter cells during cell division such that the organelles
      were present in newly formed parasites. Estimation of the volume density after 3,
      5, 7, 9, and 12 days of cultivation showed that it was lower in younger cultures,
      becoming maximal at day 9 (8.0%), but decreased in older cultures (5.9% at day
      12). Morphological changes also occurred: type I reservosomes presented an
      electron-dense matrix with lipid droplets and were characteristic of younger
      cultures, whereas type II reservosomes presented a homogeneous matrix without
      lipid inclusions and predominated in older cultures. These organelles were absent
      in bloodstream trypomastigote forms isolated from infected mice.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7809004
TI  - A multiple fission-like mode of asexual reproduction in Blastocystis hominis.
AB  - A non-axenic and an axenic isolate of Blastocystis hominis have been induced to
      form cysts in vitro using an encystation medium. The morphology of the parasite
      at different time points was observed by scanning electron microscopy. In day-2
      cultures the cysts were spherical and had a non-uniform, coarse outer surface
      around the body. A deep, pore-like opening was seen in some of the parasites.
      Most of the cysts from day-4 and day-6 cultures ruptured, revealing small,
      uniformly sized spherical bodies occurring in grape-like clusters. Acridine
      orange staining confirmed that these bodies were the progeny of Blastocystis
      hominis. A multiple fission-like reproduction process giving rise to many
      daughter Blastocystis occurs within the cyst.

PMID- 7809005
TI  - Intestinal lipid metabolism in suckling rats infected with Giardia duodenalis.
AB  - We carried out a quantitative and qualitative analysis of intestinal digestion of
      neutral lipids in suckling rats infected with Giardia duodenalis. Total lipids
      were measured after extraction from the contents of the stomach, proximal and
      distal small bowel, caecum and colon. Amounts gradually fell from the stomach to
      the colon and were identical in infected animals and controls, although high
      values were occasionally found in the caecum of infected rats. Relative glyceride
      quantities were determined by means of high-performance thin-layer
      chromatography. Triglycerides were absent from the distal small bowel, and only
      free fatty acids and cholesterol were present in the caecum, reflecting normal
      digestion of neutral lipids in infected suckling rats. Our results suggest that
      G. duodenalis does not impair intestinal fat digestion in suckling rats.

PMID- 7809007
TI  - Portal vein insulin flux and arterial glucose fluctuations in response to an oral
      meal test in islet cell-transplanted dogs.
AB  - Insulin flux was determined in the portal vein and simultaneously arterial blood
      glucose was measured before and during an oral glucose meal in conscious normal
      and pancreatic islet cell-autotransplanted dogs to test their insulinogenic
      reserve. These dogs had previously been chronically instrumented with blood flow
      probes on the portal vein and carotid artery, and blood sampling catheters in the
      portal vein, hepatic vein, carotid artery, and right external jugular vein. Such
      a model permits quantitative portal-peripheral comparisons and assessment of
      hepatic extraction. Sixteen dogs, 10 normal (N) and six long-term (2 months to 2
      yrs) islet cell-transplanted dogs (IT) were fed an oral glucose meal as a test
      (OMT). Baseline portal vein insulin fluxes (PVF) were similar in both groups
      (25.6 +/- 0.04 pmol/min in N and 24.7 +/- 19.4 pmol/min in IT). Immediately after
      OMT, PVF rose to 248.2 +/- 40.9 pmol/min in N, but only to 55.9 +/- 17.9 pmol/min
      in IT. After 30 min PVF peaked for the second time in N at 156 +/- 35.9 pmol/min,
      declining slowly to baseline after 3 h. In IT, a similar peak at 30 min was seen
      (143.7 +/- 22.1 pmol/min), declining to a value not different from baseline after
      3 h. However, cumulative insulin PV fluxes in the two groups over 3 h were not
      different. Differences were also seen in postprandial glucose fluctuations, which
      reached a maximum excursion of 11.8 +/- 0.45 mM in IT, while never rising above
      7.8 +/- 0.33 mM in N. After 3 h both groups had similar glucose values.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7809006
TI  - Epidemiologic approach to human toxocariasis in western France.
AB  - Toxocara canis is a common parasite in puppies. The danger to human health has
      not been properly established. We estimated the current incidence of this
      pathogen in two western districts of France, Loire-Atlantique and Maine et Loire.
      Blood samples from 1836 eosino-philic patients were collected and tested by an
      enzyme-linked immunosorbent assay (ELISA) excretory-secretory Toxocara antigen
      test. We obtained positive results in 22% of the cases and highly positive
      results in 7%. The ELISA data seemed to be age-dependent, with older patients
      having more positive results (P < 0.0001). The interlaboratory distribution of
      positive test results was statistically significantly different (P < 0.0001),
      suggesting regional sources. The main clinical expressions of toxocariasis were:
      asthenia, gastric pain, and pulmonary disease. Individual and collective surveys
      of this zoonotic disease need to be carried out.

PMID- 7809009
TI  - Functional state of the beta cell affects expression of both forms of glutamic
      acid decarboxylase.
AB  - Glutamic acid decarboxylase (GAD) is a candidate target autoantigen involved in
      the pathogenesis of insulin-dependent diabetes mellitus (IDDM). The functional
      state of the beta cells has been suggested to play a pathogenic role in IDDM by
      altering beta-cell autoantigen expression. In this study, we investigated
      expression of GAD-65 and GAD-67 in isolated Sprague-Dawley rat islets cultured at
      different glucose concentrations. Using GAD isoform-specific antibodies in an
      immunoblot assay, we found that expression of both GAD-65 and GAD-67 in cultured
      islets was glucose dependent and that increased expression of both forms of GAD
      correlated with increased functional state of the beta cell. Our data indicate
      that the functional state of the beta cell influences islet cell expression of
      GAD. Thus, decreasing islet cell expression of GAD by suppressing beta cells
      activity may have a potential role in blunting the autoimmune destruction of
      pancreatic islet beta cells.

PMID- 7809008
TI  - Effect of perchlorate on glucose-stimulated insulin release and 45Ca2+ uptake in
      pancreatic islets from diabetic Chinese hamsters.
AB  - Insulin release and 45Ca2+ uptake were studied in isolated islets from Chinese
      hamsters of genetically diabetic and normal sublines. The calcium channel
      agonist, perchlorate (ClO4-, 12 mmol/L), augmented both 45Ca2+ uptake and insulin
      release from normal islets in the presence of 20 but not 1 mmol/L glucose. The
      agonist also amplified the glucose-stimulated 45Ca2+ uptake and insulin release
      from diabetic islets but did not normalize the insulin release despite normal
      insulin concentration in the diabetic Chinese hamster islets. The dry weight of
      the diabetic islets was subnormal (54%, p < 0.005) but the insulin concentration
      (insulin per dry weight of islet tissue) was not different from normal (122%). It
      appears that there are defective mechanisms in addition to the glucose-stimulated
      influx of Ca2+ in diabetic islet B cells.

PMID- 7809010
TI  - Pancreatic acinar cells in adult human islets of Langerhans.
AB  - Pancreatic acinar cells within the islets of Langerhans in human pancreas were
      investigated both histopathologically and electron microscopically. Acinar cells
      inside the islets of Langerhans were observed in all 50 adult cases investigated.
      Between such acinar cells and endocrine tissues, no reticular fiber was observed;
      they were encapsulated together instead. The acinar cells were immunostained with
      antiamylase similar to the "extrainsular" acinar cells and were also connected to
      the small pancreatic duct. Electron microscopically, intercellular junctions of
      the desmosomal type were found between the acinar cells and the adjacent
      endocrine cells. Therefore, the acinar cells within the islets of Langerhans were
      true acinar cells, based on the incomplete demarcation between the islets and the
      acinar tissue.

PMID- 7809011
TI  - Endocrine cells in the rat pancreatic and bile duct system: alteration in
      diabetes.
AB  - Endocrine cells of the pancreatic and bile duct system of the diabetic rat were
      characterized with reference to their influence on duct function. In
      streptozotocin-induced diabetic rats, the endocrine cells showed various changes
      in number and topographic distribution along the epithelial lining of the duct
      system. With the exception of insulin cells, which demonstrated a marked
      decrease, the number of duct endocrine cells generally increased in the duct
      system of the diabetic animal, particularly in the terminal portion of both the
      common hepatic and the accessory pancreatic ducts encompassed by the muscle
      sphincters. Among them, the cells secreting somatostatin, a potential peptide
      inducing contraction of the muscle sphincter, showed a remarkable increase in the
      opening portion of the common hepatic and the accessory pancreatic ducts of the
      diabetic animal. The duct cells producing glucagon and pancreatic polypeptide,
      the hormones exerting an inhibitory effect on exocrine secretion of duct and
      acinar cells, also increased significantly in the duct system of the diabetic
      animal. These results suggest that the duct endocrine cells are closely related,
      not only to functional properties of the duct system, but also to disorders of
      the pancreas and biliary tract in diabetes.

PMID- 7809012
TI  - Correlation between bile acid malabsorption and pancreatic exocrine dysfunction
      in patients with chronic pancreatitis.
AB  - Fecal bile acid and fecal fat were determined in 18 normal subjects and 22
      patients with chronic pancreatitis, and the relation of fecal bile acid excretion
      to exocrine pancreatic dysfunction was studied. In chronic pancreatitis fecal
      bile acid was approximately three times that of control subjects, and large
      amounts of primary bile acid were detected. A significant correlation between
      fecal bile acid excretion and bicarbonate secreted from the pancreas was found.
      This evidence of bile acid malabsorption was not observed until bicarbonate
      output was < 0.05 mEq/h/kg. A slight correlation between fecal bile acid and
      absorption rates of fat was demonstrated. These results suggest that bile acid
      malabsorption observed in chronic pancreatitis is related to an impairment of
      pancreatic bicarbonate secretion.

PMID- 7809013
TI  - Mechanisms of stimulatory effect of neuromedin C on pancreatic exocrine secretion
      in conscious rats.
AB  - The mechanisms of the stimulatory effect of the bombesin-like peptide neuromedin
      C on pancreatic exocrine secretion were examined in conscious rats. Rats were
      prepared with cannulae draining bile and pancreatic juice separately. Intravenous
      infusion of 0.35 nmol/kg/h of neuromedin C significantly increased the secretions
      of pancreatic bicarbonate and protein, and transiently increased the plasma
      cholecystokinin (CCK) concentration. The increase in pancreatic secretion
      persisted for 90 min, whereas the increase in plasma CCK was observed only after
      15 and 30 min from the beginning of neuromedin C infusion. Intravenous infusion
      of CR-1409, a specific CCK-receptor antagonist, inhibited, but did not abolish,
      the protein secretion stimulated by neuromedin C. Intraduodenal infusion of a
      potent proton pump inhibitor, omeprazole, suppressed, but did not abolish,
      protein secretion induced by neuromedin C. Omeprazole abolished the increase in
      bicarbonate secretion produced by neuromedin C. These results indicate that
      neuromedin C induces release of CCK and that its induction of pancreatic
      hypersecretion is due to both its direct effect and CCK. The results also suggest
      that gastric hypersecretion may have a role in the bicarbonate hypersecretion
      induced by neuromedin C.

PMID- 7809014
TI  - Pharmacologic characterization of the inositol trisphosphate receptor in rat
      pancreas.
AB  - Inositol 1,4,5-trisphosphate (InsP3) is an intracellular second messenger,
      produced upon stimulation of the phosphoinositide system, capable of mobilizing
      calcium from intracellular stores. The properties of InsP3 receptor sites in the
      rat pancreas were evaluated by binding studies with InsP3 labeled with 3H.
      Specific binding was very sensitive to pH variations between 7 and 9. Kinetic
      studies showed that specific binding of InsP3 at 0 degrees C was half-maximal in
      about 10 min and reached a plateau within 60 min with a K+1 = 3.37 x 10(9) mol
      1min-1. Binding was reversible as addition of 10(-6) M unlabeled InsP3 was
      followed by dissociation of the bound ligand with a K-1 = 0.016 min-1. Scatchard
      analysis of the binding data was consistent with a single set of high-affinity
      sites with KD of 9.9 +/- 2.47 nM and a maximal binding capacity of 210 +/- 55
      fmol/mg of protein (n = 7). The specificity of [3H]InsP3 binding to these sites
      was illustrated by the much weaker affinity for structural analogs such as
      inositol 1,3,4,5-tetrakisphosphate, phytic acid, fructose 1,6-bisphosphate, and
      heparin. To assess the functional relevance of the InsP3 binding sites, the
      Ca(2+)-releasing activity of InsP3 was measured in permeabilized acinar cell
      preparations. In the presence of oligomycin (10 micrograms/ml), Ca2+ movements
      were monitored with the fluorescent indicator fura-2 (free acid). Under these
      conditions, 4 mM ATP caused rapid uptake of Ca2+ by the vesicular component of
      the acinar cells. Addition of InsP3 (0.1-15 microM) caused a dose-dependent
      release of Ca2+ with half-maximal effect at 3.2 microM.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7809015
TI  - Rat pancreatitis-associated protein is expressed in relation to severity of
      experimental pancreatitis.
AB  - To study the relation between expression of the pancreatitis-associated protein
      (PAP) and severity of pancreatitis in rats, different degrees of experimental
      pancreatitis were induced by a 1-, 3-, or 5-h cerulein infusion (5 micrograms kg
      1 h-1). This treatment decreased pancreatic volume secretion to below 10%.
      Immediately after infusion, the secretion rate increased to approximately 50% of
      control. Within 1 day, volume and bicarbonate secretion rates were not different
      from controls. At this point, protein secretion amounted to 30% of control, but
      only in animals receiving the 3- or 5-h dose. The values increased to 40-60%
      within 3 days. In all groups, the isoenzyme pattern was not influenced by the
      cerulein treatment. One day after induction of pancreatitis, the PAP was found in
      pancreatic juice in concentrations related to the dose of cerulein given. By
      immunohistochemical techniques, the protein was localized over acinar cells, but
      was not detectable in interstitial tissue, islets, or in the healthy exocrine
      pancreas. Pathomorphologic alterations in the pancreas were quantified by a
      scoring system. One and 2 days after the treatment, a more severe pancreatitis
      and more elevated levels of PAP were found in animals treated with the higher
      dose of cerulein. It is concluded that PAP is expressed in the pancreas in
      relation to the severity of cerulein-induced pancreatitis.

PMID- 7809016
TI  - Factors that affect the performance of lipase on fat digestion and absorption in
      a canine model of pancreatic insufficiency.
AB  - In a previous experiment, absorption of [14C]triolein was poor under low lipase
      in the first postcibal hour during which luminal conditions change markedly. We
      wondered how low lipase might be affected by changing concentrations of fat, bile
      salts, titratable acid, pepsin, and food particles. Therefore, in dogs with
      duodenal and midintestinal fistulas, endogenous bile and pancreatic juice were
      excluded from the intestinal lumen and replaced with varied amounts of exogenous
      bile and pancreatic enzymes during steady perfusions. Oil emulsions contained
      [14C]triolein and [3H]glycerotriether. A double isotope ratio method and a double
      isotope, double extraction method were used to determine, respectively, the
      amount of [14C]triolein absorbed and hydrolyzed by the midgut. Lipolysis
      increased with both substrate and enzyme inflows, whether inflows were varied by
      changing concentrations or rates of volume flow. But at increasing rates of fat
      entry, the percent of fat hydrolyzed by the midgut declined. Neither pH 4 nor 5
      citrate affected fat hydrolysis or absorption when titratable acid was infused at
      rates < or = 16 mEq/h; but pepsin reduced both. Whereas meat particles bound
      lipase, their presence augmented lipolysis. We speculate that rapid gastric
      emptying of fat and peptic deactivation of duodenal lipase were the main factors
      responsible for the previously poor performance of low lipase in the first
      postcibal hour.

PMID- 7809017
TI  - Early adaptation of pancreas to a protein-enriched diet: role of cholecystokinin
      and gastrin-releasing peptide.
AB  - Feeding rats a diet containing high levels of protein (as casein) increases the
      secretion and biosynthesis of pancreatic serine proteases. Cholecystokinin (CCK)
      presumably plays a role in this process although other GI peptides such as the
      gastrin-releasing peptide (GRP) may be involved. In this article, we describe the
      kinetics of pancreatic adaptation to a diet containing 45% protein as soybean and
      fish. Then we report the effect of treatment with either a cholecystokinin
      receptor antagonist (MK-329) or a gastrin-releasing peptide-receptor antagonist
      ([D-F5 Phe6, D-Ala11]-Bn(6-13)OMe, or BIM 26226) on pancreatic adaptation to this
      diet. Prior to experiments, adult male Fischer rats received a diet containing
      22% protein for 1 week. In the first experiment, 48 rats were fed a diet
      containing 45% protein; they were killed after 0-7 days. In the second
      experiment, 53 rats were fed the 22- or 45%-protein diet and received three daily
      injections of either the vehicle alone, MK-329, or BIM 26226 for 7 days before
      they were killed. When the protein-rich diet was fed for 0-7 days, amylase, in
      vitro biosynthesis, and mRNA levels were gradually decreased while serine
      protease biosynthesis was increased, reflecting the general enhancement of
      chymotrypsinogen, trypsinogen, and elastase mRNA levels. For all these
      parameters, adaptation leveled off after a 5-day feeding. When the protein diets
      were fed for 7 days, MK-329 significantly inhibited the adaptation of trypsin
      (specific activity and mRNA) and elastase (mRNAs) to the 45%-protein diet. BIM
      26226 had no effect on pancreatic adaptation to the protein-rich diet.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7809018
TI  - Pancreatitis associated with adult choledochal cysts.
AB  - We reviewed the records of 32 adult patients with choledochal cysts (CDC) to
      determine the characteristics of the associated pancreatic disease. Eighteen
      patients (56%) had 30 documented episodes of pancreatitis with epigastric pain
      and elevated serum amylase levels. Three patients developed a prolonged course
      with a pancreatic phlegmon and one patient died secondary to a pancreatic abscess
      after endoscopic retrograde cholangiopancreatography (ERCP). Pancreatitis
      occurred in all types of CDC and was not related to the age, gender or race of
      the patient. There was an association with the size of the CDC: 90% of patients
      with CDC > or = 5 cm developed pancreatitis compared with only 9% of patients
      with CDC < 5 cm (p < 0.0004). In addition, ERCP was performed in 14 patients and
      demonstrated an abnormal pancreaticobiliary duct junction in eight (57%). All
      eight patients with an abnormal pancreaticobiliary junction developed
      pancreatitis compared with only 2 out of 6 patients with normal pancreatic duct
      anatomy (p < 0.006). Patients undergoing surgical bypass rather than resection
      also tended to have higher rates of pancreatitis (80 vs. 50%). One patient with a
      Type I CDC and chronic pancreatitis was treated with surgical resection of the
      CDC and pancreatic head; this combined procedure relieved the pain. Microscopic
      examination of the CDC and the abnormal "common channel" within the pancreas
      revealed identical fibrous thickening of the duct walls with focal chronic
      inflammation and loss of surface epithelium. In conclusion, these data stress the
      previously unrecognized high incidence of symptomatic pancreatic inflammatory
      disease that accompanies adult CDC.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7809019
TI  - Lack of effect of cholecystokinin receptor antagonist (CR1505) on recovery of
      experimental pancreatitis after pancreatic duct occlusion in rats.
AB  - The effect of long term administration of a synthetic cholecystokinin (CCK)
      receptor antagonist CR1505 (loxiglumide) on pancreatitis was examined in rats
      after pancreatic duct ligation (PL) with an internal bile fistula. All rats were
      given both 6 mg/day of CR1505 continuously infused intraduodenally with an
      osmotic pump and 32 mg/day introduced into the stomach with an orogastric tube.
      Rats were killed 7, 14, and 28 days after PL, and changes of body weight,
      pancreatic wet weight, daily food intake, pancreatic protein content, and
      histology, plasma amylase concentration, and both plasma and duodenal CCK
      concentrations were examined. Administration of CR1505 for 7 days from
      immediately after PL, resulted in decrease of body weight, increase of daily food
      intake, and significant increases of intestinal CCK concentration and the level
      of CCK mRNA. However, its administration from day 7 to day 14 or 28 did not
      improve any of the parameters examined except inflammatory infiltration of the
      pancreas on the 14th postoperative day. These results suggest that CR1505 may
      have a beneficial effect on recovery from pancreatitis when administered during
      the early stage, but not when administered during a later stage.

PMID- 7809020
TI  - In vivo and in vitro effects of adenosine-5'-O-(2-thiodiphosphate) on pancreatic
      hormones in dogs.
AB  - Adenosine-5'-O-(2-thiodiphosphate) (ADP beta S), a P2y purinergic agonist, has
      been shown to be a potent insulin secretagogue on the isolated rat pancreas. In
      the present work the effects of ADP beta S on insulin somatostatin, and glucagon
      secretions were investigated in dogs. In vivo, in anesthetized fasted dogs, i.v.
      ADP beta S (0.1 mg kg-1) induced an immediate increase in insulin and
      somatostatin-like immunoreactivity (SLI) but not in glucagon pancreaticoduodenal
      outputs. In conscious fasted dogs, i.v. ADP beta S (0.1 mg kg-1) produced an
      immediate and transient augmentation in plasma insulin levels but not in plasma
      SLI and glucagon levels. In vitro, the effects of ADP beta S were investigated on
      the isolated uncinate process of dog pancreas, from normal and alloxan-diabetic
      animals. In normal uncinate process, in presence of 8.3 mM glucose, ADP beta S (1
      microM) stimulated insulin and SLI releases but not glucagon release. On uncinate
      process from diabetic animals, ADP beta S (1 microM) retained its stimulating
      effects but the responses were impaired as compared with normal dogs: Insulin
      response was drastically diminished and SLI response strongly enhanced. In
      conclusion, ADP beta S is a potent insulin secretory agent in dog. This P2y
      purinoceptor agonist, which exerts a direct stimulatory effect on pancreatic SLI,
      is interestingly devoid of direct glucagonotropic properties.

PMID- 7809021
TI  - Bombesin inhibits growth of pancreatic ductal adenocarcinoma (H2T) in nude mice.
AB  - Bombesin (BBS), a tetradecapeptide, stimulates growth of various types of cells,
      including fibroblasts and human small cell lung cancer, and has been termed the
      universal "on-switch" due to its ability to stimulate the release of numerous
      hormones. In addition, BBS receptors have been identified in normal and
      neoplastic pancreatic tissue. A pancreatic ductal adenocarcinoma cell line (H2T),
      established in our laboratory, possesses specific binding sites for BBS. The
      purpose of this study was to examine the effect of BBS on the growth of H2T
      tumors transplanted into athymic nude mice. H2T cells (5 x 10(6) cells/mouse)
      were injected s.c. into the interscapular region of the nude mice and then the
      mice were randomized into two groups (n = 10/group). Mice received either 0.1 ml
      of saline with 0.1% bovine serum albumin (BSA) (control) or 0.1 ml BBS (5
      micrograms/kg) intraperitoneally, three times/day. Tumor area was measured twice
      weekly until the mice were killed (day 32), when tumor and normal pancreas were
      removed, weighted, and assayed for DNA and protein content. Administration of BBS
      significantly inhibited H2T tumor area, weight, and DNA and protein content.
      Conversely, growth of normal pancreas, removed as an in vivo bioassay so as to
      ensure the efficacy of BBS, was stimulated. We conclude that BBS is a growth
      inhibitory factor for H2T tumors and that different mechanisms may be responsible
      for the differential growth effects elicited by normal and neoplastic pancreas in
      response to BBS.

PMID- 7809023
TI  - Pancreatic lymphoma: is it a surgical disease?
AB  - Primary pancreatic lymphoma is a rare neoplasm that reportedly regresses promptly
      with aggressive chemotherapy. Recently, the role of surgical management has been
      relegated to biopsy alone. The aim of this study was to review our experience
      with primary pancreatic lymphoma and to determine the outcome of patients managed
      by radiation therapy and/or chemotherapy. From 1952 to 1991, 107 patients with
      non-Hodgkin's lymphoma involving the pancreas were identified. Twelve patients
      (11%) had primary pancreatic lymphoma. The presenting symptoms and signs were
      nonspecific: abdominal pain (83%), weight loss (50%), and a palpable mass (58%).
      Six of the 12 patients (50%) undergoing celiotomy had a preoperative diagnosis of
      pancreatic carcinoma. These lymphomas were large (x = 8 +/- 2 cm) and deemed
      unresectable because of size, alleged mesenteric vessel encroachment, regional
      lymph node metastasis, or because of an intraoperative diagnosis of lymphoma.
      Biopsy alone was performed in 50% of patients and biliary bypass and/or
      gastroenterostomy was performed in 25% of patients. A single resection
      (pancreatoduodenectomy) was performed 1 year after a full course of chemotherapy
      had failed. Ten patients, all of whom died of progressive lymphoma, received
      primary postoperative radiation therapy and/or chemotherapy, and no patient was
      disease-free at follow-up. Mean survival was 13 months for patients who received
      chemotherapy alone (n = 2), 22 months for those treated with radiation therapy
      only (n = 5), and 26 months for those receiving combined radiation therapy and
      chemotherapy (n = 3).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7809022
TI  - Lovastatin inhibits pancreatic cancer growth regardless of RAS mutation.
AB  - Lovastatin, an inhibitor of the rate-limiting enzyme of cholesterol synthesis,
      inhibits growth of pancreatic cancer cells. A possible mechanism of this
      inhibition is that lovastatin inhibits the activity of RAS protein by depleting
      farnesyl (an intermediate of cholesterol synthesis). The K-ras gene is frequently
      mutated in pancreatic cancers and RAS protein requires farnesyl to be bound to
      the cell membrane and thereby activated. To investigate whether lovastatin
      inhibition of cell growth depends upon the presence of ras mutation, codons 12/13
      and 61 of ras genes were examined by the dideoxynucleotide chain-terminating
      method in five pancreatic cell lines (human CAPAN2, CAV, MIA Paca2, PANCi, and
      hamster H2T) on which lovastatin exerted a growth-inhibitory effect. These codons
      play a major role in tumorigenic mutation of ras genes. Lovastatin inhibited cell
      growth by 99% (MIA), 97% (H2T), 78% (CAV), 41% (CAPAN2), and 23% (PANC1),
      respectively, when cells were treated with 2.5 micrograms/ml lovastatin for 6
      days. Activating point mutations were found in codon 12 of the K-ras gene (wild
      type:GGT) in MIA (GTT), H2T (GAT), CAPAN2 (TGT), and PANC1 (GAT) but not in CAV.
      In addition, the CAV cell line did not have a mutation in either H- or N-ras
      genes. Lovastatin inhibited the growth of CAV cells even though this cell line
      did not have ras mutation, suggesting that lovastatin inhibition of pancreatic
      cancer cell growth is not directly dependent on the presence of ras mutation.

PMID- 7809024
TI  - Pseudolymphoma of the pancreas mimicking cancer.

PMID- 7809025
TI  - Pefloxacin and pancreatic islet function.

PMID- 7809026
TI  - Thermosensitive mutants of Aspergillus awamori glucoamylase by random
      mutagenesis: inactivation kinetics and structural interpretation.
AB  - Seven thermosensitive glucoamylase mutants generated by random mutagenesis and
      expressed in Saccharomyces cerevisiae were sequenced and their inactivation
      kinetics were determined. Wild-type glucoamylase expressed in S. cerevisiae was
      more glycosylated and more stable than the native Aspergillus niger enzyme. All
      mutants had lower free energies of inactivation than wild-type glucoamylase. In
      the Ala39-->Val, Ala302-->Val and Leu410-->Phe mutants, small hydrophobic
      residues were replaced by larger ones, showing that increases in size and
      hydrophobicity of residues included in hydrophobic clusters were destabilizing.
      The Gly396-->Ser and Gly407-->Asp mutants had very flexible residues replaced by
      more rigid ones, and this probably induced changes in the backbone conformation
      that destabilized the protein. The Pro128-->Ser mutation changed a rigid residue
      in an alpha-helix to a more flexible one, and destabilized the protein by
      increasing the entropy of the unfolded state. The Ala residue in the Ala442-->Thr
      mutation is in the highly O-glycosylated region surrounded by hydrophilic
      residues, where it may be a hydrophobic anchor linking the O-glycosylated arm to
      the catalytic core. It was replaced by a residue that potentially is O
      glycosylated. In five of the seven mutations, residues that were part of
      hydrophobic microdomains were changed, confirming the importance of the latter in
      protein stability and structure.

PMID- 7809027
TI  - Identification of the reactive cysteine in clostridial glutamate dehydrogenase by
      site-directed mutagenesis and proof that this residue is not strictly essential.
AB  - Cys320 of clostridial glutamate dehydrogenase, a residue close to the coenzyme
      binding site, has been replaced by serine. The mutant enzyme was successfully
      overproduced and purified by using the normal protocol for the wild-type enzyme
      and also behaved indistinguishably from wild-type enzyme on native and SDS-PAGE.
      The specific activity was significantly enhanced in assays at both pH 7 (+90%)
      and pH 8 (+38%). Detailed initial-rate kinetics revealed that at pH 7 this
      increase was mainly attributable to a higher maximum rate, since the Km values
      for both substrates were marginally increased. In the mutant enzyme the
      inactivating reaction with DTNB that characterizes the wild-type enzyme is
      completely eliminated. This proves that inactivation of the wild-type enzyme is
      due to modification of Cys320, that nevertheless Cys320 is not strictly essential
      for catalytic activity and that the remaining cysteine residue at position 144 is
      inaccessible to DTNB. Provision of an engineered subunit with a correct native
      structure but with its DTNB titre decreased from 1 to 0 mol/mol now offers a
      valuable tool for counting subunits in hybrid oligomers.

PMID- 7809028
TI  - Multivalent Fvs: characterization of single-chain Fv oligomers and preparation of
      a bispecific Fv.
AB  - Single-chain Fv proteins are known to aggregate and form multimeric species. We
      report here that these molecules represent a new class of molecular assembly,
      which we have termed multivalent Fvs. Each binding site in a multivalent Fv
      comprises the variable light-chain (VL) domain from a single-chain Fv, and the
      variable heavy-chain (VH) domain from a second single-chain Fv. Each single-chain
      Fv in a multivalent Fv is part of two binding sites. We have characterized the
      multivalent forms of the 4-4-20, CC49 and B6.2 sFvs. The degree of multivalent Fv
      formation is linker-dependent. Multivalent Fvs cannot form in the absence of an
      intact linker. Multivalent Fvs can be stabilized by their antigen. The conversion
      between different forms of the multivalent Fvs can be catalyzed by disassociating
      agents such as 0.5 M guanidine hydrochloride with 20% ethanol. Multivalent Fvs
      have significantly different stabilities depending on the specific variable
      domains from which they are constructed. Two models have been proposed for the
      structure of a multivalent Fv. We have tested each model by attempting to produce
      a heterodimer from the anti-fluorescein 4-4-20 and anti-tumor CC49 variable
      regions. We successfully produced a 4-4-20/CC49 heterodimer that comprises two
      mixed sFvs. The first mixed sFv is composed of the 4-4-20 VL domain, a 12 residue
      linker and the CC49 Vh domain. The second mixed sFv is composed of a CC49 VL
      domain, a 12 residue linker and the 4-4-20 VH domain. The 4-4-20/CC49 heterodimer
      bound both fluorescein and the tumor-associated glycoprotein-72 antigen. These
      results support a VH/VL 'rearrangement' model in which each variable domain of a
      multivalent Fv binding site comes from a different polypeptide chain.

PMID- 7809029
TI  - Multimerization behaviour of single chain Fv variants for the tumour-binding
      antibody B72.3.
AB  - A systematic study has been performed on the relationship between linker length,
      relative orientation of variable domains, multimerization behaviour and antigen
      binding activity for single chain Fvs (scFvs) of the tumour-binding antibody
      B72.3. Thirteen scFv variants with linkers comprising up to six repeats of the
      motif Gly-Gly-Gly-Gly-Ser were studied. All these scFvs showed a tendency to form
      dimers or higher molecular weight species, and this tendency decreased with
      increasing linker length. The dimers and higher molecular weight forms may arise
      from head to tail intermolecular association of VH and VL domains. For each
      linker length, scFvs with the organization VL-linker-VH showed greater binding
      activity than those with the organization VH-linker-VL. In fact, for the latter
      organization only the variant with a 30 amino acid linker showed good binding
      activity, suggesting that (i) for B72.3 the C-terminus of VH or the N-terminus of
      VL makes a structural contribution to antigen binding, and (ii) shorter linkers
      interfere with this contribution. Antigen binding studies on scFvs should be
      interpreted with caution because of their tendency to multimerize. Such
      multimerization can be minimized by using linkers longer than those in common
      use.

PMID- 7809030
TI  - Folding and stability of the active N-terminal domain of tissue inhibitor of
      metalloproteinases-1 and -2.
AB  - The truncated forms of tissue inhibitor of metalloproteinase-1 and -2 (delta TIMP
      1 and -2), comprising the N-terminal active domain, are ideal molecules for
      structural analysis by intrinsic fluorescence as each contains a single conserved
      tryptophan residue. In this paper we describe studies on their conformational
      stability, unfolding/refolding kinetics and the environment of the unique
      tryptophan as judged by its fluorescence properties in the native state and
      exposure to an external quencher, acrylamide. Two forms of delta TIMP-2 were
      studied: delta TIMP-2 T21 derived from the full-length cDNA clone isolated from a
      mixed-tumour library, and delta TIMP-2 A21 containing the highly conserved
      V18IRAK22 sequence. In all three delta TIMP proteins the tryptophan environments
      in the native state appeared to be similar, but substantial differences were seen
      in their conformational stabilities and refolding kinetics. delta TIMP-1 was
      approximately twice as stable as delta TIMP-2 T21 and 1.4-fold more stable than
      delta TIMP-2 A21. This stability difference between delta TIMP-1 and delta TIMP-2
      was shown to be independent of N-linked glycosylation. delta TIMP-1 and delta
      TIMP-2 A21 both showed simple two-state refolding kinetics, whereas delta TIMP-2
      T21 refolding was more complex and biphasic in character. These differences
      between delta TIMP-2 T21 and A21 suggest that residue 21 is a structurally
      important site in the TIMP protein. All three truncated molecules can be
      considered as stable independent folding domains ideally suited for further
      structural analysis.

PMID- 7809031
TI  - A new approach to artificial and modified proteins: theory-based design,
      synthesis in a cell-free system and fast testing of structural properties by
      radiolabels.
AB  - A novel approach to the creation of artificial and modified proteins has been
      elaborated. The approach includes a sequence design based on the molecular theory
      of protein secondary structure and folding patterns, gene expression in a cell
      free system and testing of structural properties of the synthesized polypeptides
      at a nanogram level using radiolabelled chains. The approach has been applied to
      a new synthetic protein albebetin which has been designed to form a 3-D fold
      which does not contradict any structural rule but has been never observed up to
      now in natural proteins. Using size-exclusion chromatography, urea-gradient
      electrophoresis and limited proteolysis of a radiolabelled chain, it has been
      shown that the artificial protein is nearly as compact as natural proteins,
      cooperatively unfolds at high urea concentrations and has some structural
      features of a definite structure consistent with the designed one. As albebetin
      has been designed as consisting of two structural repeats, a 'half-albebetin'
      (one of these repeats) has also been synthesized and studied. It was shown that
      'half-albebetin' is also compact.

PMID- 7809032
TI  - Engineering hyperexpression of bacteriophage Mu C protein by removal of secondary
      structure at the translation initiation region.
AB  - The structure at the translation initiation region (TIR) of mRNA has pronounced
      regulatory effects on gene expression. Our attempts to overexpress the C gene of
      bacteriophage Mu in a variety of expression vectors resulted in low yields of
      protein. Analysis of Mu C mRNA shows the potential to form a secondary structure
      involving a ribosome binding site and AUG codon. We have engineered the
      overproduction of the protein using a PCR-aided cloning approach to remove the
      sequences involved in the formation of this secondary structure. The
      overexpressing clone, under the control of T7 gene 10 promoter in a T7 expression
      system yielded > 30% of total cell protein. The difference in mRNA structure
      between expressing and non-expressing clones was confirmed by electrophoretic
      analysis of run-off transcripts. The overexpressed protein was purified in a
      single step by site-specific DNA affinity chromatography. The purified
      recombinant protein was active in band shift assays. DNA binding activity
      required Mg2+ and was weak in the presence of Mn2+. Cd2+ or Zn2+ could not
      support DNA binding. Under optimal conditions, the equilibrium binding constant
      (Kapp) was determined to be 2 x 10(12) M-1.

PMID- 7809033
TI  - Modular mutagenesis of a TIM-barrel enzyme: the crystal structure of a chimeric
      E. coli TIM having the eighth beta alpha-unit replaced by the equivalent unit of
      chicken TIM.
AB  - The crystal structure of a hybrid Escherichia coli triosephosphate isomerase
      (TIM) has been determined at 2.8 A resolution. The hybrid TIM (ETIM8CHI) was
      constructed by replacing the eighth beta alpha-unit of E. coli TIM with the
      equivalent unit of chicken TIM. This replacement involves 10 sequence changes.
      One of the changes concerns the mutation of a buried alanine (Ala232 in strand 8)
      into a phenylalanine. The ETIM8CHI structure shows that the A232F sequence change
      can be incorporated by a side-chain rotation of Phe224 (in helix 7). No cavities
      or strained dihedrals are observed in ETIM8CHI in the region near position 232,
      which is in agreement with the observation that ETIM8CHI and E.coli TIM have
      similar stabilities. The largest CA (C-alpha atom) movements, approximately 3 A,
      are seen for the C-terminal end of helix 8 (associated with the outward rotation
      of Phe224) and for the residues in the loop after helix 1 (associated with
      sequence changes in helix 8). From the structure it is not clear why the kcat of
      ETIM8CHI is 10 times lower than in wild type E.coli TIM.

PMID- 7809034
TI  - Comparison of systematic search and database methods for constructing segments of
      protein structure.
AB  - Two principal methods of determining the conformation of short pieces of
      polypeptide backbone in proteins have been developed: using a database of known
      structures and systematically generating all conformations. In this paper, we
      compare the effectiveness of these two techniques. The completeness of the
      database for segments of different lengths is examined and it is found to contain
      most conformations for segments seven residues long, but to deteriorate rapidly
      for longer regions. When the database segment is to be incorporated into the rest
      of a structure, at least seven residues are required to build four new residues,
      because of the need to position the segment relative to the rest of the
      structure. It is found that such positioning using flanking residues results in
      large errors in the inserted region. We conclude that the database method is
      currently not effective for comparative modeling, even for short segments. The
      systematic search procedure is found to generate almost all structures of short
      segments found in proteins. In contrast to the database method, low root mean
      square error structures are obtained for a set of trial segments embedded in the
      rest of a protein structure. Thus, it should be considered the method of choice.

PMID- 7809035
TI  - Torsion angle differences as a means of pinpointing local polypeptide chain
      trajectory changes for identical proteins in different conformational states.
AB  - We discuss a facile and sensitive method of determining conformational
      differences based on the changes in the phi and psi angle values between
      chemically identical proteins in different conformations. It complements the
      conventional r.m.s. deviation technique, but offers some advantages. Two classes
      of conformational difference can be distinguished by this method: (i) abrupt
      local trajectory deformations where the chains flanking the locus of deformation
      remain simultaneously superposable and (ii) localized 'hinge bending' that
      generates domain shifts, thereby causing only one domain to be superposable on
      the other at one time. In the second case, the r.m.s. deviation method requires
      two or more calculations of r.m.s. deviation as a function of sequence after
      optimal alignment of each domain to demonstrate the superposability of the
      shifted domains, and hence the conservation of internal domain structure. On the
      other hand, the method of plotting delta phi and/or delta psi as a function of
      sequence demonstrates in one graph the superposability of shifted domains,
      without the prior need to perform rotational and translational alignments whose
      outcomes vary with the subjective choice of alignment parameters. Also, an
      analysis of the r.m.s. deviation in C alpha alone will miss torsion angle
      rotations that happen to preserve C alpha positions. The method pinpoints
      residues contributing singly to localized, major movements of a conformational
      change; however, it is insensitive to conformational changes achieved through
      small, concerted movements spread over a number of residues.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7809036
TI  - Cooperative deformation of a de novo designed protein.
AB  - A de novo protein design has been made to understand the unique packing of
      natural proteins that have a beta/alpha-barrel fold. A carefully designed 207
      amino acid sequence was synthesized using an Escherichia coli expression system
      and the structural and thermodynamic characteristics of the purified protein were
      studied. At neutral pH the protein is soluble and monomeric, with large amounts
      of secondary structure and a hydrophobic core, although the broad resonance peaks
      of its NMR spectrum suggest that the designed protein does not have a unique
      structure with tightly packed side chains. In an H-D exchange experiment, no
      amido protons of the designed protein exchanged slowly with deuterons. At acidic
      pH, thermal unfolding was observed with a remarkable change in the excess heat
      capacity measured directly by a differential scanning microcalorimeter. The
      enthalpy and entropy differences at 110 degrees C, extrapolated from analyzed
      thermodynamic parameters, are approximately 1/3 of the common values for natural
      proteins. These measurements indicate that the folding is significantly
      cooperative as expected, but that the protein is still loosely packed.

PMID- 7809037
TI  - Structural basis for the difference in thermodynamic properties between the two
      cysteine proteinase inhibitors human stefins A and B.
AB  - Homology modelling has been used to model stefin A based on the X-ray structure
      of stefin B. Several models have been produced by interactive modelling or
      positioning of the side chains by Monte Carlo procedure with simulated annealing.
      The quality of models was evaluated by calculation of the free energy of
      hydration, 3D-1D potential or buried area of surface accessibility. Stefin A is a
      thermostable protein, exhibiting a two-state denaturation, while stefin B
      denatures at a 40 degrees C lower temperature and forms a stable molten globule
      intermediate under mild denaturing conditions. From the tertiary structures,
      thermodynamic functions were predicted, conforming closely to the experimental
      calorimetric results. Polar and apolar buried areas of surface accessibility were
      obtained by structural deconvolution of the thermograms. It is suggested that the
      basic difference between the stefins is the domination of hydrophobic interaction
      in the stabilization of stefin B, which is due to its non-specific nature leading
      to the formation of a molten globule intermediate. Modelling of stefin A predicts
      increased numbers of hydrogen bonds which stabilize it and increase the
      cooperativity of its denaturation.

PMID- 7809038
TI  - Maintenance of the hydrophobic face of the diphtheria toxin amphipathic
      transmembrane helix 1 is essential for the efficient delivery of the catalytic
      domain to the cytosol of target cells.
AB  - The transmembrane (T) domain of diphtheria toxin (DT) comprises nine alpha
      helices and has been shown to play an essential role in the efficient delivery of
      the catalytic (C) domain of DT across the eukaryotic cell membrane and into the
      cytosol. We have demonstrated recently that the first three amphipathic helixes
      of the T domain, although not necessary for either channel formation or receptor
      binding, are required for the efficient transmembrane delivery of the C domain.
      In the present study, we have performed a detailed structure-function analysis of
      T domain helix 1 (TH1) of the DT-related fusion protein DAB389IL-2. We performed
      exchange and site-directed mutagenesis of TH1 and the resulting mutant fusion
      toxins were analyzed by gel electrophoresis and tested for their efficiencies in
      the delivery of the C domain to the cell cytosol. We demonstrate that the overall
      charge distribution and hydrophobicity of amino acids in the amphipathic helix
      TH1, rather than a specific amino acid sequence, are critical for the function of
      this helix. The insertion of a charged residue in the hydrophobic face of TH1
      abolishes cytotoxic activity, whereas replacement of a hydrophobic residue by a
      charged amino acid in the hydrophilic face of the helix has little, if any,
      effect on cytotoxic activity. In addition, we have identified Ser220 by site
      directed mutagenesis as a residue that appears to be critical for correct folding
      of the fusion toxin. Mutations in this position result in fusion proteins that
      are extremely sensitive to proteolytic attack.

PMID- 7809039
TI  - Novel substrate specificity engineered in the arabinose binding protein.
AB  - The L-arabinose binding protein (ABP) of Escherichia coli naturally binds L
      arabinose and D-galactose with very high affinity and, with reduced affinity, a
      variety of other sugars that differ only at the C5 position of the pyranose ring.
      However, there are stringent specificity requirements at the 1, 2, 3 and 4
      positions. Based on the high resolution crystallographic structure of the ligand
      protein complex, remodelling of the binding pocket was attempted to shift the
      specificity towards C1-substituted galactosides. To create space in the vicinity
      of the reducing end of bound galactose, four residues, Lys10, Asp90, Thr147 and
      Leu145, have been mutated for residues with smaller side chains. Forty-seven
      mutants containing different combinations of these mutations were tested by
      fluorometry for their ability to bind methyl-beta-D-galactoside (met-beta-Gal) or
      iso-propyl-beta-D-thio-galactoside (IPTG). Two double-residue mutants carrying
      Ser at position 147 and Ala or Gly at position 90 appeared of particular interest
      for being able to bind met-beta-Gal or IPTG, respectively, and no longer
      galactose. Fluorescence experiments and molecular modelling indicate that the
      mode of binding of the new substrates to the mutant proteins might be similar to
      that of the natural ligands to wild-type ABP.

PMID- 7809040
TI  - DNA recognition code of transcription factors in the helix-turn-helix, probe
      helix, hormone receptor, and zinc finger families.
AB  - We have previously reported that in four transcription factor families the DNA
      recognition rules can be described as (i) chemical rules, which list possible
      pairings between the 20 amino acid residues and the four DNA bases, and (ii)
      stereochemical rules, which describe the base and amino acid positions in
      contact. We have incorporated these rules into a computer program and examined
      the nature of the rules. Here we conclude that the DNA recognition rules are
      simple, logical, and consistent. The rules are specific enough to predict DNA
      binding characteristics from a protein sequence.

PMID- 7809041
TI  - Singlet molecular oxygen evolution upon simple acidification of aqueous
      hypochlorite: application to studies on the deleterious health effects of
      chlorinated drinking water.
AB  - A study of the pH profile of the decomposition of aqueous hypochlorite has
      revealed the evolution (onset at pH 8) of single (1 delta g) molecular oxygen
      (singlet spin state dioxygen) detected spectroscopically (1268 nm), prior to the
      appearance of chlorine (onset at pH 5.5). The possible mechanism of the singlet
      state dioxygen evolution is presented, and the origin of its chloride ion
      dependence is discussed, especially in reference to chloride ion dependence of
      singlet molecular oxygen evolution in biological systems. Recent epidemiological
      analyses of the correlation of human cancer with chlorinated water supplies focus
      attention on the singlet oxygen mechanisms of DNA lesion formation.

PMID- 7809042
TI  - Singlet molecular oxygen in the Haber-Weiss reaction.
AB  - Characteristic chemiluminescence emission of singlet (1 delta g) molecular oxygen
      at 1268 nm is reported from a Haber-Weiss reaction. The reaction consists of
      mixing aqueous hydrogen peroxide with a solution of potassium superoxide,
      solubilized by 18-crown-6 ether in carbon tetrachloride or in dry acetonitrile at
      room temperature. Since the discovery of the enzyme superoxide dismutase by J.M.
      McCord and I. Fridovich [(1968) J. Biol. Chem. 243, 5733-5760], the identity of
      the reactive oxidant in superoxide-generating systems in biology has remained a
      chemical mystery. The results presented here suggest strongly that the reactive
      species is singlet oxygen generated via the Haber-Weiss reaction and not, as
      usually assumed, the hydroxyl radical, .OH, generated by the same reaction.

PMID- 7809043
TI  - Adenovirus-mediated transfer of the HST-1 (FGF4) gene induces increased levels of
      platelet count in vivo.
AB  - The HST-1 (fibroblast growth factor 4, FGF4) protein is a potent mitogen for a
      variety of cell types of mesodermal and neuroectodermal origin, including
      fibroblasts, endothelial cells, and melanocytes in vitro. To identify the cells
      and tissue targets of HST-1 in vivo, adenovirus-mediated HST-1 gene transfer was
      performed. In nude mice, intraperitoneal injection of 3 x 10(9) plaque-forming
      units of adenoviruses carrying the HST-1 gene (Adex1HST-1L) caused an increase in
      the number of platelets in the peripheral blood. The number of platelets reached
      twice the pretreated level by 12 days after the virus injection and the increased
      level continued up to 20-30 days thereafter. Administration of recombinant HST-1
      protein resulted in a transient increase in the platelet count. The number of
      megakaryocytes in the bone marrow and spleen of the animals with Adex1HST-1L was
      increased compared with the control animals. Other hematological changes
      attributed to HST-1 were not observed. Although the mechanisms involved in
      increased levels of platelet count by HST-1 protein remain to be elucidated,
      these findings also suggest that adenovirus with the HST-1 gene may be
      efficiently used for the treatment of thrombocytopenia in various diseases.

PMID- 7809044
TI  - Selective clustering of glutamate and gamma-aminobutyric acid receptors opposite
      terminals releasing the corresponding neurotransmitters.
AB  - Several immunocytochemical and physiological studies have demonstrated a
      concentration of neurotransmitter receptors at postsynaptic sites on neurons, but
      an overall picture of receptor distribution has not emerged. In particular, it
      has not been clear whether receptor clusters are selectively localized opposite
      terminals that release the corresponding neurotransmitter. By using antibodies
      against the excitatory glutamate receptor subunit GluR1 and the inhibitory type A
      gamma-aminobutyric acid (GABA) receptor beta 2/3 subunits, we show that these
      different receptor types cluster at distinct postsynaptic sites on cultured rat
      hippocampal neurons. The GABAA receptor beta 2/3 subunits clustered on cell
      bodies and dendritic shafts opposite GABAergic terminals, whereas GluR1 clustered
      mainly on dendritic spines and was associated with glutamatergic synapses.
      Chronic blockade of evoked transmitter release did not block receptor clustering
      at postsynaptic sites. These results suggest that complex mechanisms involving
      nerve terminal-specific signals are required to allow different postsynaptic
      receptor types to cluster opposite only appropriate presynaptic terminals.

PMID- 7809045
TI  - Peroxynitrite induces both vasodilatation and impaired vascular relaxation in the
      isolated perfused rat heart.
AB  - The effects of the oxidant species peroxynitrite (ONOO-) on coronary perfusion
      pressure and vasodilatation elicited by acetylcholine, isoproterenol, and S
      nitroso-N-acetyl-DL-penicillamine were investigated in the isolated perfused rat
      heart. ONOO- (0.3-1000 microM) caused a concentration-dependent vasodilatation of
      the coronary vasculature. This dilator response was inhibited by oxyhemoglobin,
      indicating that it was due to the generation of nitric oxide. Tachyphylaxis to
      ONOO- developed rapidly, so that the response disappeared after three or four
      applications of this compound. ONOO- not only induced tachyphylaxis but also
      inhibited the vasodilatation induced by the three vasodilators studied. This
      latter effect of ONOO- was critically dependent on its concentration, since it
      occurred at 3 microM, which was subthreshold as a dilator, and at 1000 microM,
      which was supramaximal, but not at 30 and 100 microM. These latter concentrations
      inhibited the responses to vasodilators only in the presence of oxyhemoglobin.
      Thus, a wide range of concentrations of ONOO- induce a vascular dysfunction, as
      evidenced by the tachyphylaxis to its own vasodilator actions and the long
      lasting impairment of the responses to other vasodilators. However, at the same
      time ONOO- generates nitric oxide, which at certain concentrations of ONOO- is
      sufficient to counteract its deleterious action. Coinfusion of S-nitroso-N-acetyl
      DL-penicillamine or prostacyclin at low concentrations that did not produce
      vasodilatation also protected against ONOO(-)-induced vascular dysfunction: these
      compounds may be protective through a common mechanism, as yet undefined.

PMID- 7809046
TI  - Stereospecific dihaloalkane binding in a pH-sensitive cavity in cubic insulin
      crystals.
AB  - Crystallographic analysis at 2-A resolution of the selective binding of
      dihalogenated methane, ethane, and ethylene compounds in the cavity on the cubic
      insulin dimer axis provides a model for anesthetic-protein interactions. At pH 6
      11, 1,2-dichloroethane binds isomorphically in the right-handed cis-conformation,
      displacing four water molecules from the invariant cavity. Lowering the pH to 5.7
      in 1 M Na2SO4 without dihaloalkanes induces a cooperative structural transition
      in which the dyad cavities between B13 glutamate pairs are constricted, and SO4(2
      ) ions are bound by rearranged triads of B1 NH+3 groups. In the presence of
      dichloroethane at pH 5-5.5, the equilibrium is shifted to a mixture of the ligand
      bound and ligand-excluding cavity structures, with half-occupancy of the sulfate
      sites, exemplifying how a volatile anesthetic can act as an allosteric effector.
      Measurements at pH 9 of the occupancies of structurally similar dihaloalkanes
      demonstrate a high degree of binding selectivity. Induced polarization of the
      ligand and bound water by the charge distribution in the binding cavity
      apparently provides the selective electrostatic interactions that discriminate
      between dihaloalkanes of comparable size and polarity.

PMID- 7809047
TI  - Interaction of two LysR-type regulatory proteins CatR and ClcR with heterologous
      promoters: functional and evolutionary implications.
AB  - The soil bacteria Pseudomonas putida can use benzoate or 3-chlorobenzoate as a
      sole carbon source. Benzoate and 3-chlorobenzoate are converted into catechol and
      3-chlorocatechol, respectively, which are in turn converted into tricarboxylic
      acid cycle intermediates. The catabolic pathways of both compounds proceed
      through similar intermediates, have similar genetic organization, and have
      homologous enzymes responsible for different catabolic steps. This has led to
      suggestions that the plasmid-borne 3-chlorocatechol degradation genes evolved
      from the chromosomal catechol degradation genes. Both catechol and 3
      chlorocatechol pathways are positively regulated by the homologous regulatory
      proteins CatR and ClcR, respectively. These proteins belong to the LysR family of
      DNA binding proteins and bind to highly conserved target sequences. We examined
      the ability of CatR and ClcR to cross-regulate the two pathways. CatR was shown
      in vitro by DNase I footprinting and gel-shift assays to interact with the clcABD
      promoter region. Likewise, ClcR was shown to interact in vitro with the catBC
      promoter region. In in vivo experiments, CatR complemented a ClcR- P. putida
      strain harboring the clcABD operon for growth on 3-chlorobenzoate. However, ClcR
      was not capable of complementing a CatR- P. putida strain for growth on benzoate.
      These observations were confirmed by lacZ-transcriptional fusion expression
      experiments. Differences in the CatR and ClcR binding sites and their in vitro
      binding characteristics may explain the ability of CatR and not ClcR to cross
      activate. These differences may provide insight about the evolution of regulatory
      systems in P. putida.

PMID- 7809048
TI  - Binding of the human papillomavirus E1 origin-recognition protein is regulated
      through complex formation with the E2 enhancer-binding protein.
AB  - The papillomavirus E1 and E2 proteins form heteromeric complexes and individually
      bind specific sequences within the viral origin of replication. The mechanism by
      which these proteins are recruited to the origin and the role of the E1/E2
      complex in replication remain undefined. To examine the interplay of these
      replication proteins, we have analyzed the binding of human papillomavirus (HPV)
      type 31b E1 and E2 proteins to the origin of replication. Binding of E1 to the
      origin was increased by E2 proteins and required the presence of E2 binding
      sites. This increase was due to the formation of E1/E2 complexes which
      preferentially bound E2-responsive sequences, and the magnitude was determined by
      the relative affinity of the E2 binding sites. While the E1 protein alone bound
      an A/T-rich sequence at the HPV-31b origin with low affinity, complexes of E1 and
      E2 bound instead to E2 binding sites with high affinity. The E1/E2 complex bound
      a similar sequence as E2 homodimers, but only E2 homodimer binding induced a
      significant increase in hypersensitivity as indicated by DNase I footprinting. In
      the presence of excess E1, E1 proteins bound both the A/T-rich sequence and E2
      binding sites through complex formation with E2. In E2 excess, E1/E2 complexes
      preferentially formed, and binding was specific for E2 sites. Therefore, changes
      in the relative amounts of E1 and E2 proteins can dramatically alter the pattern
      of binding of viral replication factors to the origin. These observations suggest
      a model whereby modulation of the relative levels of E1 and E2 during the viral
      life cycle may alter the pattern of origin binding and possibly episomal copy
      number.

PMID- 7809049
TI  - The essential light chain is required for full force production by skeletal
      muscle myosin.
AB  - Myosin, a molecular motor that is responsible for muscle contraction, is composed
      of two heavy chains each with two light chains. The crystal structure of
      subfragment 1 indicates that both the regulatory light chains (RLCs) and the
      essential light chains (ELCs) stabilize an extended alpha-helical segment of the
      heavy chain. It has recently been shown in a motility assay that removal of
      either light chain markedly reduces actin filament sliding velocity without a
      significant loss in actin-activated ATPase activity. Here we demonstrate by
      single actin filament force measurements that RLC removal has little effect on
      isometric force, whereas ELC removal reduces isometric force by over 50%. These
      data are interpreted with a simple mechanical model where subfragment 1 behaves
      as a torque motor whose leyer arm length is sensitive to light-chain removal.
      Although the effect of removing RLCs fits within the confines of this model,
      altered crossbridge kinetics, as reflected in a reduced unloaded duty cycle,
      probably contributes to the reduced velocity and force production of ELC
      deficient myosins.

PMID- 7809050
TI  - Lazaroids improve the survival of grafted rat embryonic dopamine neurons.
AB  - In rodent models of Parkinson disease in which transplants of dissociated rodent
      and human embryonic mesencephalic tissue, rich in dopamine neurons, have been
      studied, only 5-20% of the dopamine neurons survive the implantation procedure.
      We have investigated the effects of inhibiting free radical generation with two
      lazaroids, U-74389G and U-83836E, on the survival of embryonic rat dopamine
      neurons. U-74389G is a 21-aminosteroid, and U-83836E combines the piperazinyl
      pyrimidine portion of 21-aminosteroids with the antioxidant ring of alpha
      tocopherol. In an initial study, we found that the lazaroids markedly prolonged
      the period after tissue dissociation that an embryonic mesencephalic cell
      suspension exhibits high cell viability in vitro, as assessed by using a dye
      exclusion method. In a second series of experiments, addition of lazaroids to
      dissociated mesencephalic graft tissue increased the yield of surviving rat
      dopamine neurons 2.6-fold after implantation in the dopamine-denervated rat
      striatum. The improved survival correlated with an earlier onset of graft-induced
      functional effects in the amphetamine-induced rotation test. Thus, inhibition of
      free radical generation can significantly increase the yield of grafted embryonic
      dopamine neurons. Addition of lazaroids to the graft preparation is a relatively
      simple modification of the transplantation protocol and could readily be applied
      in a clinical setting. Moreover, since iron-dependent lipid peroxidation has been
      suggested to play a role in the death of nigral dopamine neurons in Parkinson
      disease and lazaroids are particularly potent inhibitors of such processes, the
      findings may have implications for the pathogenesis of this disease.

PMID- 7809051
TI  - Two separate areas of the brain differentially guide the development of a song
      control nucleus in the zebra finch.
AB  - A brain nucleus that is important for the generation of song in the adult male
      zebra finch (Poephila guttata), the robust nucleus of the archistriatum (RA),
      receives dual inputs from two other telencephalic song nuclei: the hyperstriatum
      ventrale pars caudale (HVc) and the lateral magnocellular nucleus of the anterior
      neostriatum (L-MAN). We lesioned each of these afferent inputs to the RA early in
      development, either by themselves or both at the same time in the same side of
      the brain, to determine what influences each of these nuclei exerts on the normal
      development of the RA into adulthood. We found that lesioning the HVc in a 20-day
      old male zebra finch prevents the later increase in RA volume and soma size that
      would normally occur around 35 days post-hatching. MAN lesions at this same early
      age, on the other hand, had a large effect on reducing the volume and cell number
      of RA neurons, without affecting soma size. Lesioning both inputs early in
      development induced considerable RA neuronal cell death and atrophy of the
      nucleus. This study shows that the development of the RA is affected differently
      by each of its two input nuclei.

PMID- 7809052
TI  - Eicosanoids mediate insect nodulation responses to bacterial infections.
AB  - We propose that nodule formation is mediated by eicosanoids in insects.
      Nodulation is the temporally and quantitatively predominant cellular defense
      response to bacterial infection in insects and other invertebrates. Inhibition of
      eicosanoid biosynthesis in larvae of the tobacco hornworm Manduca sexta
      immediately prior to intrahemocoelic infections with the bacterium Serratia
      marcescens strongly reduced the nodulation response. Inhibition of eicosanoid
      biosynthesis also reduced formation of cellular aggregates at 1 hr postinfection,
      which indicates that eicosanoids mediate early stages of nodulation. Separate
      treatments with specific inhibitors of phospholipase A2, cyclooxygenase, and
      lipoxygenase reduced nodulation, which supports the view that nodule formation is
      a complex process involving prostaglandins and lipoxygenase products. The
      inhibitory effects of the phospholipase A2 inhibitor dexamethasone on nodulation
      were apparent by 1 hr after infection, and the effects increased, relative to
      controls, over 24 hr. The dexamethasone effects were expressed in a dose
      dependent manner, and they were reversed by treating infected insects with
      eicosanoid-precursor polyunsaturated fatty acids. Treatments with the saturated
      fatty acid 16:0, which is not an eicosanoid precursor, did not reverse the
      dexamethasone effects on nodulation. These findings strongly support the
      identification of nodulation as a specific insect cellular defense mechanism that
      is mediated by eicosanoids.

PMID- 7809054
TI  - Expression of apple 1-aminocyclopropane-1-carboxylate synthase in Escherichia
      coli: kinetic characterization of wild-type and active-site mutant forms.
AB  - The pyridoxal phosphate-dependent enzyme 1-aminocyclopropane-1-carboxylate
      synthase (ACC synthase; S-adenosyl-L-methionine methylthioadenosine-lyase, EC
      4.4.1.14) catalyzes the conversion of S-adenosylmethionine (AdoMet) to ACC and 5'
      methylthioadenosine, the committed step in ethylene biosynthesis in plants. Apple
      ACC synthase was overexpressed in Escherichia coli (3 mg/liter) and purified to
      near homogeneity. A continuous assay was developed by coupling the ACC synthase
      reaction to the deamination of 5'-methylthioadenosine by adenosine deaminase
      (adenosine aminohydrolase, EC 3.5.4.4) from Aspergillus oryzae. The enzyme is
      dimeric, with kcat = 9s-1 per monomer and Km = 12 microM for AdoMet. The
      pyridoxal phosphate-binding site of ACC synthase appears to be highly homologous
      to that of aspartate aminotransferase, suggesting similar roles for corresponding
      residues. Site-directed mutagenesis of Lys-273, Arg-407, and Tyr-233
      (corresponding to residues 258, 386, and 225 in aspartate aminotransferase) and
      kinetic analyses of the mutants confirms their importance in the ACC synthase
      mechanism. The Lys-273 to Ala mutant has no detectable activity, supporting the
      identification of this residue as the base catalyzing C alpha proton abstraction.
      Mutation of Arg-407 to Lys results in a precipitous drop in kcat/Km and an
      increase in Km for AdoMet of at least 20-fold, in accordance with its proposed
      role as principal ligand for the substrate alpha-carboxylate group. Replacement
      of Tyr-233 with Phe causes a 24-fold increase in the Km for AdoMet and no change
      in kcat, suggesting that this residue plays a role in orienting the pyridoxal
      phosphate cofactor in the active site.

PMID- 7809053
TI  - An isoform of transcription factor CREM expressed during spermatogenesis lacks
      the phosphorylation domain and represses cAMP-induced transcription.
AB  - cAMP response element-binding protein (CREB) and modulator protein (CREM)
      regulate the transcription of cAMP-responsive genes via phosphorylation by cAMP
      dependent protein kinase A. Reverse transcription and polymerase chain
      amplification of RNA from male germ cells identify an alternatively spliced CREM
      isoform, CREM delta C-G, lacking four exons including those encoding the protein
      kinase A-regulated phosphorylation domain and the flanking glutamine-rich
      transcriptional activation domains. CREM delta C-G retains exons that encode the
      basic-leucine zipper (bZIP) DNA-binding domain, binds to cAMP response elements
      (CREs), and competitively inhibits binding of CREB and CREM to CREs. Expression
      of CREM delta C-G inhibits transcription of a CRE-containing chloramphenicol
      acetyltransferase reporter plasmid induced by endogenous CREB. Antiserum to CREM
      detects CREM delta C-G in elongated spermatids from rat testis. These
      observations indicate that CREM delta C-G is a unique form of a competitive
      negative regulator of CREB-mediated gene transcription expressed in a maturation
      dependent manner in haploid germ cells. The developmental specificity of CREM
      delta C-G suggests that it may play a role in transcriptional regulation during
      spermatogenesis.

PMID- 7809055
TI  - Three chemically distinct types of oxidants formed by iron-mediated Fenton
      reactions in the presence of DNA.
AB  - Exposure of Escherichia coli to H2O2 leads to two kinetically distinguishable
      modes of killing: mode I killing occurs maximally near 2 mM H2O2, whereas mode II
      killing is essentially independent of H2O2 concentrations up to 20 mM. A major
      portion of H2O2 toxicity is attributed to DNA damage caused by the iron-mediated
      Fenton reaction. By studying DNA damage during Fenton reactions in vitro, the
      same complex kinetics were observed and three types of oxidants were
      distinguished based upon their reactivities toward H2O2 and alcohols and upon
      iron-chelator effects. Type I oxidants are sensitive to H2O2 but moderately
      resistant to ethanol; type II oxidants are resistant to both H2O2 and ethanol;
      type III oxidants are sensitive to H2O2, ethanol, and t-butanol. To explain these
      results, we hypothesize that type I oxidants are generated upon Fe2+ associated
      with DNA only through electrostatic interactions and cause mode I killing of E.
      coli; type II oxidants arise upon Fe2+, which is at least partially base
      associated, and cause mode II killing; type III oxidants arise on Fe2+ free in
      solution and probably do not cause killing. Therefore, particular interactions of
      DNA with transition metals should be considered to be an integral part of the
      chemistry and toxicity of H2O2.

PMID- 7809056
TI  - Replication of the genomic RNA of a positive-strand RNA animal virus from
      negative-sense transcripts.
AB  - Studies of RNA replication among the positive-strand RNA animal viruses have been
      hindered by the apparent inability of their RNA-dependent RNA polymerases to
      initiate replication on the corresponding negative-sense RNAs. However, here I
      report that in the case of the nodavirus flock house virus (FHV), which has a
      bipartite positive-sense RNA genome, the viral RNA replicase can replicate a
      negative-sense transcript of the genome segment that encodes the viral capsid
      proteins. For this work, the FHV replication cycle was experimentally
      reconstructed in baby hamster kidney cells that were transfected with specialized
      transcription plasmids designed to direct the synthesis of RNAs which
      corresponded closely to the two genome segments of FHV. The RNA replicase encoded
      by the larger genome segment could utilize either the positive or the negative
      strand of the smaller segment as a template, and it catalyzed RNA replication to
      produce similar RNA products in the two situations. Surprisingly, studies of the
      nucleotide sequences that were required for replication showed that the 3' end of
      the negative-strand RNA contained only a minimal cis-acting signal. The success
      of these experiments will facilitate further studies of the cis- and trans-acting
      factors involved in the recognition and replication of negative-sense RNA in this
      system.

PMID- 7809058
TI  - Universal biological scaling and mortality.
AB  - Universal scaling relations for basal metabolism, heart rate, and life-span are
      presented in a physically transparent form with no adjustable parameters. Their
      accuracy is a few percent for animals ranging from invertebrates to mammals. They
      suggest that natural death is related to irreparable molecular damage to specific
      cells or molecules.

PMID- 7809057
TI  - Transcriptional activation of a ras-like gene (kir) by oncogenic tyrosine
      kinases.
AB  - We report the characterization of a member of the ras gene family that is
      overexpressed in cells transformed by abl tyrosine kinase oncogenes. The gene,
      named kir (for kinase-inducible ras-like), is induced at the transcriptional
      level. kir mRNA has a rapid turnover and encodes a protein of 33 kDa with guanine
      nucleotide-binding activity but undetectable intrinsic GTPase activity. kir was
      cloned by differential screening of genes present in fully malignant versus
      growth factor-independent cell lines expressing wild-type or mutant forms of
      BCR/ABL. BCR/ABL and v-Abl induce transcription of the kir gene via specific
      signaling pathway(s), but kir overexpression alone is not sufficient to mediate
      transformation.

PMID- 7809060
TI  - Visual motion induces synchronous oscillations in turtle visual cortex.
AB  - In mammalian brains, multielectrode recordings during sensory stimulation have
      revealed oscillations in different cortical areas that are transiently
      synchronous. These synchronizations have been hypothesized to support integration
      of sensory information or represent the operation of attentional mechanisms, but
      their stimulus requirements and prevalence are still unclear. Here I report an
      analogous synchronization in a reptilian cortex induced by moving visual stimuli.
      The synchronization, as measured by the coherence function, applies to spindle
      like 20-Hz oscillations recorded with multiple electrodes implanted in the dorsal
      cortex and the dorsal ventricular ridge of the pond turtle. Additionally,
      widespread increases in coherence are observed in the 1- to 2-Hz band, and
      widespread decreases in coherence are seen in the 10- and 30- to 45-Hz bands. The
      20-Hz oscillations induced by the moving bar or more natural stimuli are
      nonstationary and can be sustained for seconds. Early reptile studies may have
      interpreted similar spindles as electroencephalogram correlates of arousal;
      however, the absence of these spindles during arousing stimuli in the dark
      suggests a more specific role in visual processing. Thus, visually induced
      synchronous oscillations are not unique to the mammalian cortex but also occur in
      the visual area of the primitive three-layered cortex of reptiles.

PMID- 7809059
TI  - Source of nuclear calcium signals.
AB  - Transient increases of Ca2+ concentration in the nucleus regulate gene expression
      and other nuclear processes. We investigated whether nuclear Ca2+ signals could
      be regulated independently of the cytoplasm or were controlled by cytoplasmic
      Ca2+ signals. A fluorescent Ca2+ indicator that is targeted to the nucleus was
      synthesized by coupling a nuclear localization peptide to Calcium Green dextran,
      a 70-kDa Ca2+ indicator. Stimulation of rat basophilic leukemia cells by antigen
      or by photolytic uncaging of inositol 1,4,5-trisphosphate induced transient
      increases in nuclear and cytosolic Ca2+ concentrations. Elevations in the nuclear
      Ca2+ concentration followed those in the nearby perinuclear cytosol within 200
      ms. Heparin-dextran, an inhibitor of the inositol 1,4,5-trisphosphate receptor
      that is excluded from the nucleus, was synthesized to specifically block the
      release of Ca2+ from cytosolic stores. Addition of this inhibitor suppressed Ca2+
      transients in the nucleus and the cytosol. We conclude that the Ca2+ level in the
      nucleus is not independently controlled. Rather, nuclear Ca2+ increases follow
      cytosolic Ca2+ increases with a short delay most likely due to Ca2+ diffusion
      from the cytosol through the nuclear pores.

PMID- 7809061
TI  - Nuclear assembly is independent of linker histones.
AB  - The role of linker histones in the assembly of functional nuclei was examined
      with the use of a cell-free extract of Xenopus eggs that transforms condensed
      sperm chromatin into DNA-replication-competent pronuclei. When linker histones
      were removed from the extract, the resultant pronuclei were indistinguishable
      from those formed in the complete extract. The assembly of functional nuclear
      membrane, nuclear lamina, and prereplication centers allowed identical DNA
      replication efficiencies. Thus, linker histones are not required for the assembly
      of morphologically normal nuclei capable of DNA replication.

PMID- 7809062
TI  - Crystal structure of fructose-1,6-bisphosphatase complexed with fructose 2,6
      bisphosphate, AMP, and Zn2+ at 2.0-A resolution: aspects of synergism between
      inhibitors.
AB  - The crystal structure of fructose-1,6-bisphosphatase (Fru-1,6-Pase; EC 3.1.3.11)
      complexed with Zn2+ and two allosteric regulators, AMP and fructose 2,6
      bisphosphate (Fru-2,6-P2) has been determined at 2.0-A resolution. In the refined
      model, the crystallographic R factor is 0.189 with rms deviations of 0.014 A and
      2.8 degrees from ideal geometries for bond lengths and bond angles, respectively.
      A 15 degrees rotation is observed between the upper dimer C1C2 and the lower
      dimer C3C4 relative to the R-form structure (fructose 6-phosphate complex),
      consistent with that expected from a T-form structure. The major difference
      between the structure of the previously determined Fru-2,6-P2 complex (R form)
      and that of the current quaternary T-form complex lies in the active site domain.
      A zinc binding site distinct from the three binding sites established earlier was
      identified within each monomer. Helix H4 (residues 123-127) was found to be
      better defined than in previously studied ligated Fru-1,6-Pase structures.
      Interactions between monomers in the active site domain were found involving H4
      residues from one monomer and residues Tyr-258 and Arg-243 from the adjacent
      monomer. Cooperativity between AMP and Fru-2,6-P2 in signal transmission probably
      involves the following features: an AMP site, the adjacent B3 strand (residues
      113-118), the metal site, the immediate active site, the short helix H4 (residues
      123-127), and Tyr-258 and Arg-243 from the adjacent monomer within the upper (or
      lower) dimer. The closest distance between the immediate active site and that on
      the adjacent monomer is only 5 A. Thus, the involvement of H4 in signal
      transmission adds another important pathway to the scheme of the allosteric
      mechanism of Fru-1,6-Pase.

PMID- 7809063
TI  - Identification of synaptic proteins and their isoform mRNAs in compartments of
      pancreatic endocrine cells.
AB  - Several proteins that are of importance for membrane trafficking in the nerve
      terminal have recently been characterized. We have used Western blot and
      immunohistochemistry to show that synaptotagmin, synaptobrevin/VAMP (vesicle
      associated membrane protein), SNAP-25 (synaptosomal-associated protein of 25
      kDa), and syntaxin proteins are present in cells of the islets of Langerhans in
      the endocrine pancreas. Synaptotagmin-like immunoreactivity (-LI) was localized
      to granules within the cytoplasm of a few endocrine cells located in the
      periphery of the islets, identified as somatostatin-containing cells, and in many
      nerve fibers within the islets. VAMP-LI was seen in granules of virtually all
      pancreatic islet cells and also in nerve fibers. SNAP-25-LI and syntaxin-LI were
      predominantly present in the plasma membrane of the endocrine cells, including
      insulin-producing beta cells. In situ hybridization, using isoform-specific
      oligonucleotide probes, detected VAMP-2, cellubrevin, SNAP-25, syntaxin 1A, 4,
      and 5, and munc-18 mRNAs in isolated pancreatic islets and in insulin-producing
      cells. The results show the presence of several synaptic proteins at protein and
      mRNA levels in pancreatic islet cells, suggesting that they may have specific
      roles in the molecular regulation of exocytosis also in insulin-secreting cells.

PMID- 7809064
TI  - Comparison of the heat shock response in ethnically and ecologically different
      human populations.
AB  - In response to heat shock or other metabolic insults, an increased expression of
      different heat shock proteins (hsps) and, in particular, members of the hsp70
      family is observed in human cells. Using two-dimensional electrophoresis, we
      compared the pattern of hsp70 synthesis in human fibroblast cell lines isolated
      from two contrasting groups of individuals. The first group was represented by
      native Turk-men living in the hot desert of Middle Asia; the second group
      consisted of Russians living in moderate climatic regions of European Russia.
      This analysis has shown that fibroblasts isolated from Turkmen after severe heat
      shock exhibited intensive synthesis of all hsps in parallel with synthesis of
      many other cellular proteins, while only trace synthesis of hsps was observed in
      the second group (Russians). Surprisingly, Northern analysis of RNA synthesis
      failed to reveal any differences between the two groups after heat shock
      treatment. When survival of fibroblasts after severe heat shock treatment was
      assessed by colony formation assay, the cells of the first group exhibited
      significantly higher survival rates.

PMID- 7809065
TI  - Hereditary eosinophil peroxidase deficiency: immunochemical and spectroscopic
      studies and evidence for a compound heterozygosity of the defect.
AB  - Hereditary eosinophil peroxidase (EPO; EC 1.11.1.7) deficiency is a rare
      abnormality of eosinophil granulocytes characterized by decreased or absent
      peroxidase activity and decreased volume of the granule matrix. The molecular
      basis of the defect is not known. We report here its molecular characterization
      in an EPO-deficient subject and his family members. The EPO-deficient eosinophils
      contained EPO-related material as determined immunochemically using either
      monoclonal or polyclonal anti-EPO antibodies but had no spectroscopic evidence of
      EPO. Eosinophil precursors from the EPO-deficient subject contained normally
      sized EPO mRNA, which was reverse transcribed into the corresponding cDNA clones
      encompassing the whole gene. Sequencing of these clones disclosed two mutations,
      a G-->A transition causing a nonconservative replacement of an arginine residue
      with a histidine and an insertion causing a shift in the reading frame with the
      appearance of a premature stop codon. The two mutations were located on different
      chromosomes indicating a compound heterozygosity for the defect. Both the son and
      the daughter of the proband inherited the G-->A transition, and their eosinophils
      contained a peroxidase activity intermediate between that of control subjects and
      the proband, suggesting that the transition is a deficiency-causing mutation.
      Eosinophil precursors from the EPO-deficient subject were found to actively
      synthesize an EPO that was apparently normal in terms of cytochemical reaction
      for peroxidase and immunoreactivity with monoclonal and polyclonal anti-EPO
      antibodies, but spectroscopically abnormal. The cytochemical reaction for
      peroxidase tended to decrease or disappear in the eosinophil precursors of the
      EPO-deficient subject but not of a normal subject as differentiation went on,
      suggesting that the Arg-->His substitution causes the production of an unstable
      EPO that undergoes progressive degradation as the cells mature.

PMID- 7809066
TI  - Wavelength mutations and posttranslational autoxidation of green fluorescent
      protein.
AB  - The green fluorescent protein (GFP) of the jellyfish Aequorea victoria is an
      unusual protein with strong visible absorbance and fluorescence from a p
      hydroxybenzylidene-imidazolidinone chromophore, which is generated by cyclization
      and oxidation of the protein's own Ser-Tyr-Gly sequence at positions 65-67.
      Cloning of the cDNA and heterologous expression of fluorescent protein in a wide
      variety of organisms indicate that this unique posttranslational modification
      must be either spontaneous or dependent only on ubiquitous enzymes and reactants.
      We report that formation of the final fluorophore requires molecular oxygen and
      proceeds with a time constant (approximately 4 hr at 22 degrees C and atmospheric
      pO2) independent of dilution, implying that the oxidation does not require
      enzymes or cofactors. GFP was mutagenized and screened for variants with altered
      spectra. The most striking mutant fluoresced blue and contained histidine in
      place of Tyr-66. The availability of two visibly distinct colors should
      significantly extend the usefulness of GFP in molecular and cell biology by
      enabling in vivo visualization of differential gene expression and protein
      localization and measurement of protein association by fluorescence resonance
      energy transfer.

PMID- 7809067
TI  - One subspecies of the red junglefowl (Gallus gallus gallus) suffices as the
      matriarchic ancestor of all domestic breeds.
AB  - The noncoding control region of the mitochondrial DNA of various gallinaceous
      birds was studied with regard to its restriction fragment length polymorphism
      (RFLP) and sequences of the first 400 bases. Tandem duplication of the 60-base
      unit was established as a trait unique to the genus Gallus, which is shared
      neither by pheasants nor by quails. Unlike its close ally Gallus varius (green
      junglefowl), the red junglefowl Gallus gallus is a genetically very diverse
      species; the 7.0% sequence divergence was seen between those from Thailand (G. g.
      gallus and G. g. spadiceus) and the other from the Indonesian island of Java (G.
      g. Bankiva). Furthermore, the divergence increased to 27.83% if each transversion
      is regarded as an equivalent of 10 transitions. On the other hand, a mere 0.5
      3.0% difference (all transitions) separated various domestic breeds of the
      chicken from two G. g. gallus of Thailand, thus indicating a single domestication
      event in the area inhabited by this subspecies of the red junglefowl as the
      origin of all domestic breeds. Only transitions separated six diverse
      domesticated breeds. Nevertheless, a 2.75% difference was seen between RFLP type
      I breeds (White Leghorn and Nagoya) and a RFLP type VIII breed (Ayam Pelung). The
      above data suggested that although the mitochondrion of RFLP type V was the main
      contributor to domestication, hens of other RFLP types also contributed to this
      event.

PMID- 7809068
TI  - Transposition of the LINE-like retrotransposon TART to Drosophila chromosome
      termini.
AB  - TART, a telomere-associated DNA element from Drosophila, is shown in this paper
      to have structural homology to LINE (long interspersed element)-like
      retrotransposons and to transpose to broken chromosome ends. TART DNA was
      detected by in situ hybridization in 7 of 10 independent additions of DNA to a
      chromosome end. We found evidence that a TART element had transposed to the
      chromosome end in each of two additions that were examined in detail. From the
      DNA sequence of a TART element that recently transposed, we infer that TART
      encodes two proteins having significant sequence similarity to the putative
      proteins of many LINEs. These results support the hypothesis that TART elements
      preferentially retrotranspose to the termini of chromosomes as part of the
      essential process by which Drosophila telomeres are maintained.

PMID- 7809069
TI  - Ras activation of genes: Mob-1 as a model.
AB  - The ras oncogenes function by indirectly controlling expression of a subset of
      yet-undefined genes that are crucial for cell growth and differentiation. In a
      differential display strategy, numerous genes were identified on the basis of
      their differential expression in rat embryo fibroblasts transformed by the
      cooperation of mutant Ha-ras and p53 genes. We demonstrate here that one such
      gene, designated mob-1, is a downstream target of the Ras signaling pathway. The
      417-bp mob-1 promoter, which contains dual NF-kappa B and AP-1 binding sites,
      confers the Ras inducibility. Oncogenic Ras as well as serum growth factors that
      activate endogenous Ras can induce mob-1 expression, but with a fundamental
      difference in that the oncogenic induction is constitutive whereas the serum
      induction is transient. mob-1 encodes a small secretory protein with a high
      degree of homology to IP-10, a member of a proinflammatory cytokine family. These
      findings link chronic inflammatory response to constitutive ras activation and
      tumorigenesis. Mob-1 may serve as a secreted marker for oncogenic Ha-ras
      mutations.

PMID- 7809070
TI  - The DNA-activated protein kinase is required for the phosphorylation of
      replication protein A during simian virus 40 DNA replication.
AB  - The 32-kDa subunit of replication protein A (RPA) is phosphorylated during the S
      phase of the cell cycle in vivo and during simian virus 40 DNA replication in
      vitro. To explore the functional significance of this modification, we purified a
      HeLa cell protein kinase that phosphorylates RPA in the presence of single
      stranded DNA. By several criteria we identified the purified enzyme as a form of
      the DNA-activated protein kinase (DNA-PK), a previously described high molecular
      weight protein kinase that is capable of phosphorylating a number of nuclear DNA
      binding proteins. Phosphorylation of RPA by DNA-PK is stimulated by natural
      single-stranded DNAs but not by homopolymers lacking secondary structure. Studies
      with the simian virus 40 model system indicate that DNA-PK is required for DNA
      replication-dependent RPA phosphorylation. Depletion of the kinase activity,
      however, has no effect on the extent of DNA replication in vitro. Our data
      support a model in which phosphorylation of RPA by DNA-PK is activated by
      formation of replication intermediates containing single- and double-stranded
      regions. This event may be involved in a signaling mechanism that coordinates DNA
      replication with the cell cycle.

PMID- 7809071
TI  - A mutation in ribosomal protein L9 affects ribosomal hopping during translation
      of gene 60 from bacteriophage T4.
AB  - Ribosomes hop over a 50-nt coding gap during translation of gene 60 mRNA from
      bacteriophage T4. This event occurs with near-unitary efficiency when gene 60
      lacZ fusions are expressed in Escherichia coli. One of the components necessary
      for this hop is an RNA hairpin structure containing the 5' junction of the 50-nt
      coding gap. A mutant E. coli was isolated and found to significantly increase
      hopping when carrying gene 60-lacZ constructs with altered hairpins. The
      mutation, hop-1, changed Ser93 to Phe in rplI, the gene coding for ribosomal
      large-subunit protein L9. Ribosomal hopping on a synthetic sequence in the
      absence of a hairpin was also increased by this mutation. These data suggest that
      hop-1 may substitute for the function of the hairpin during ribosomal hopping.

PMID- 7809072
TI  - Identification of the TCL1 gene involved in T-cell malignancies.
AB  - The TCL1 locus on chromosome 14q32.1 is frequently involved in chromosomal
      translocations and inversions with one of the T-cell receptor loci in human T
      cell leukemias and lymphomas. The chromosome 14 region translocated or rearranged
      involves approximately 350 kb of DNA at chromosome band 14q32.1. Within this
      region we have identified a gene coding for a 1.3-kb transcript, expressed only
      in restricted subsets of cells within the lymphoid lineage and expressed at high
      levels in leukemic cells carrying a t(14;14)(q11;q32) chromosome translocation or
      a inv(14)(q11;q32) chromosome inversion. The cognate cDNA sequence reveals an
      open reading frame of 342 nt encoding a protein of 14 kDa. The TCL1 gene
      sequence, which, to our knowledge, shows no sequence homology with other human
      genes, is preferentially expressed early in T- and B-lymphocyte differentiation.

PMID- 7809073
TI  - Phytochrome assembly in living cells of the yeast Saccharomyces cerevisiae.
AB  - The biological activity of the plant photoreceptor phytochrome requires the
      specific association of a linear tetrapyrrole prosthetic group with a large
      apoprotein. As an initial step to develop an in vivo assay system for structure
      function analysis of the phytochrome photoreceptor, we undertook experiments to
      reconstitute holophytochrome in the yeast Saccharomyces cerevisiae. Here we show
      that yeast cells expressing recombinant oat apophytochrome A can take up
      exogenous linear tetrapyrroles, and, in a time-dependent manner, these pigments
      combine with the apoprotein to form photoactive holophytochrome in situ. Cell
      viability measurements indicate that holophytochrome assembly occurs in living
      cells. Unlike phytochrome A in higher plant tissue, which is rapidly degraded
      upon photoactivation, the reconstituted photoreceptor appears to be light stable
      in yeast. Reconstitution of photoactive phytochrome in yeast cells should enable
      us to exploit the power of yeast genetics for structure-function dissection of
      this important plant photoreceptor.

PMID- 7809074
TI  - Subtiligase: a tool for semisynthesis of proteins.
AB  - A variant of subtilisin BPN', which we call subtiligase, has been used to ligate
      esterified peptides site-specifically onto the N termini of proteins or peptides
      in aqueous solution and in high yield. We have produced biotinylated or heavy
      atom derivatives of methionyl-extended human growth hormone (Met-hGH) by ligating
      it onto synthetic peptides containing biotin or mercury. Polyethylene glycol
      (PEG)-modified atrial natriuretic peptide (ANP) was produced by ligating ANP onto
      peptides containing sites for PEG modification. We have established the N
      terminal sequence requirements for efficient ligation onto proteins, using either
      synthetic substrates or pools of filamentous phage containing Met-hGH with random
      N-terminal sequences (substrate phage). To facilitate ligations involving
      proteins with highly structured or buried N termini, a more stable subtiligase
      was designed that effectively ligates peptides onto Met-hGH even in 4 M guanidine
      hydrochloride. The use of subtiligase should expand the possibilities for protein
      semisynthesis and rational protein design.

PMID- 7809075
TI  - Genetic selection of growth-inhibitory sequences in mammalian cells.
AB  - To assess the role of mitogenically activated genes in the control of cell
      proliferation, we have taken a genetic approach based on the premise that
      blocking the function of an essential gene should lead to growth inhibition.
      Using a newly developed selection procedure, we isolated growth-inhibitory
      sequences from a pool of random cDNA fragments of 19 growth-related genes
      associated with the G0/G1 transition. These sequences encode potential dominant
      negative variants of c-Fos, JunB, and p44MAPK that may interfere with their
      growth-related functions. We anticipate that this procedure, which allows for the
      selection of sequences that cause a growth-inhibition phenotype, may have broad
      applications in the identification and analysis of genes that regulate cell
      growth.

PMID- 7809076
TI  - Spontaneous and restriction enzyme-induced chromosomal recombination in mammalian
      cells.
AB  - We have derived Chinese hamster ovary (CHO) cell hybrids containing herpes
      simplex virus thymidine kinase (tk) heteroalleles for the study of spontaneous
      and restriction enzyme-induced interchromosomal recombination. These lines
      allowed us to make a direct comparison between spontaneous intrachromosomal and
      interchromosomal recombination using the same tk heteroalleles at the same
      genomic insertion site. We find that the frequency of interchromosomal
      recombination is less by a factor of at least 5000 than that of intrachromosomal
      recombination. Our results with mammalian cells differ markedly from results with
      Saccharomyces cerevisiae, with which similar studies typically give only a 10-to
      30-fold difference. Next, to inquire into the fate of double-strand breaks at
      either of the two different Xho I linker insertion mutations, we electroporated
      PaeR7I enzyme, an isoschizomer of Xho I, into these hybrids. A priori, these
      breaks can be repaired either by recombination from the homology or by end
      joining. Despite a predicted bias against recovering end-joining products in our
      system, all cells characterized by enzyme-induced resistance to
      hypoxanthine/aminopterin/thymidine were, in fact, due to nonhomologous
      recombination or end-joining. These results are in agreement with other studies
      that used extrachromosomal sequences to examine the relative efficiencies of end
      joining and homologous recombination in mammalian cells, but are in sharp
      contrast to results of analogous studies in S. cerevisiae, wherein only products
      of homologous events are detected.

PMID- 7809077
TI  - Infection of vaginal and colonic epithelial cells by the human immunodeficiency
      virus type 1 is neutralized by antibodies raised against conserved epitopes in
      the envelope glycoprotein gp120.
AB  - The rectal and genital tract mucosae are considered to be major sites of entry
      for the human immunodeficiency virus (HIV) during sexual contact. We now
      demonstrate that vaginal epithelial cells can be infected by HIV type 1 (HIV-1)
      via a mechanism similar to that described for neuroglial cells and, more
      recently, for colorectal epithelial cells, involving initial interaction of the
      HIV-1 envelope glycoprotein gp120 with a cell-surface glycosphingolipid (sulfated
      lactosylceramide). A hyperimmune serum against gp120 was able to neutralize HIV-1
      infection of vaginal epithelial cells. Site-directed immunization was employed to
      identify sites on gp120 recognized by antibodies neutralizing HIV-1 infection of
      vaginal and colonic epithelial cells. Hyperimmune sera were raised in monkeys
      against a series of 40 overlapping synthetic peptides covering the entire
      sequence of HIV-1 (HTLV-IIIB) gp120. Antisera raised against five synthetic
      peptides, corresponding to three relatively conserved regions and to the
      hypervariable region (V3 loop), efficiently neutralized HIV-1 infection of human
      vaginal epithelial cells in vitro. Similar results were obtained with the colonic
      cells. Hyperimmune sera to all five peptides have been shown earlier to
      neutralize HIV-1 infectivity in CD4+ T cells. These results have obvious
      implications for the design of mucosal subunit vaccines against sexually
      transmitted HIV-1 infections.

PMID- 7809078
TI  - Altered striatal function in a mutant mouse lacking D1A dopamine receptors.
AB  - Of the five known dopamine receptors, D1A and D2 represent the major subtypes
      expressed in the striatum of the adult brain. Within the striatum, these two
      subtypes are differentially distributed in the two main neuronal populations that
      provide direct and indirect pathways between the striatum and the output nuclei
      of the basal ganglia. Movement disorders, including Parkinson disease and various
      dystonias, are thought to result from imbalanced activity in these pathways.
      Dopamine regulates movement through its differential effects on D1A receptors
      expressed by direct output neurons and D2 receptors expressed by indirect output
      neurons. To further examine the interaction of D1A and D2 neuronal pathways in
      the striatum, we used homologous recombination to generate mutant mice lacking
      functional D1A receptors (D1A-/-). D1A-/- mutants are growth retarded and die
      shortly after weaning age unless their diet is supplemented with hydrated food.
      With such treatment the mice gain weight and survive to adulthood.
      Neurologically, D1A-/- mice exhibit normal coordination and locomotion, although
      they display a significant decrease in rearing behavior. Examination of the
      striatum revealed changes associated with the altered phenotype of these mutants.
      D1A receptor binding was absent in striatal sections from D1A-/- mice. Striatal
      neurons normally expressing functional D1A receptors are formed and persist in
      adult homozygous mutants. Moreover, substance P mRNA, which is colocalized
      specifically in striatal neurons with D1A receptors, is expressed at a reduced
      level. In contrast, levels of enkephalin mRNA, which is expressed in striatal
      neurons with D2 receptors, are unaffected. These findings show that D1A-/- mice
      exhibit selective functional alterations in the striatal neurons giving rise to
      the direct striatal output pathway.

PMID- 7809079
TI  - New Cretaceous marsupial from Mongolia and the early radiation of Metatheria.
AB  - A marsupial mammal from Mongolia representing a previously unreported group,
      Asiadelphia, offers unequivocal evidence that metatherians were represented on
      the continent of Asia during the Late Cretaceous (Campanian), even in the
      northern arid interior. Asiatherium is known by skull, left and right mandibles,
      and most of its postcranial skeleton. Comparisons of the dentition, ear region,
      and aspects of the postcranium not only allow its diagnosis as an Asian group of
      metatherians but also permit a diagnosis of the Metatheria based on the
      unequivocally apomorphous condition of the dental formula and probable
      replacement pattern of the protometatherian, in contrast to the more primitive
      therian dental formula, represented by the few known Aegialodontidae and the
      first dental eutherians. It appears an inescapable conclusion that the first
      metatherians had a more derived dental formula (and probably replacement pattern)
      than the earliest dental eutherians, regardless of what specific derivation from
      a therian ancestry is contemplated. Such a diagnosis also supports the
      metatherian status of other Cretaceous Asian and American taxa such as the
      Deltatheroida and Kokopellia. The hypothesis that Metatheria originated in North
      America is largely dependent on the preponderance of Cretaceous forms from North
      America and negative evidence from Asia (i.e., on the lack of lower latitude
      Early Cretaceous tropical faunas). Conversely, the relative Cretaceous paucity of
      placentals from North America and their greater abundance in Asia suggests the
      earliest flowering of the Eutheria in an unspecified region of the Old World. The
      concept of a holophyletic Theria (= Tribosphenida) employed here, based on the
      biologically significant apomorphy of the molar form-function of the first
      therian, entails only the tribosphenic mammals (infraclasses Tribotheria,
      Metatheria, and Eutheria) but not the sundry quasi-triangular-toothed mammals and
      their derivatives in the Mesozoic (Eupantotheria, Peramura, Monotremata, etc.).
      It is suggested that the Asiadelphia and Deltatheroida, the protospecies of both,
      with the apomorphic therian dental formula, are ancient lineages of Metatheria
      independent from their North American relatives probably since the early part of
      the Late Cretaceous.

PMID- 7809081
TI  - Physiological cytosolic Ca2+ transients evoke concurrent mitochondrial
      depolarizations.
AB  - Calcium, a ubiquitous second messenger, stimulates the activity of several
      mitochondrial dehydrogenases. This has led to the suggestion that the same
      messenger that signals cell activation could also activate mitochondrial
      electron/proton transport, thereby meeting demands for increased cellular energy.
      To test this in live cells, quantitative three-dimensional microscopy and ratio
      imaging were used to measure membrane potential of individual mitochondria and
      cytosolic calcium distribution. Mitochondria reversibly depolarized as cytosolic
      calcium rose and then fell following physiological stimulation. Thus, the
      dominant response of the mitochondrion to a rise in cytosolic [Ca2+] is to draw
      on the electrochemical potential, possibly to accelerate processes directly
      involved in ATP synthesis and calcium homeostasis.

PMID- 7809082
TI  - Chimeric dopamine-norepinephrine transporters delineate structural domains
      influencing selectivity for catecholamines and 1-methyl-4-phenylpyridinium.
AB  - The dopamine (DA) and norephinephrine (NE) transporters demonstrate important
      differences in their selectivity for catecholamines and the parkinsonism-inducing
      neurotoxin 1-methyl-4-phenylpyridinium (MPP+), yet their primary sequences and
      predicted topology are strikingly similar. To delineate discrete structural
      domains contributing to pharmacologic and kinetic differences between the DA and
      NE transporters, a series of recombinant chimeras was generated by a restriction
      site-independent method and expressed in mammalian cells. Functional analyses of
      the chimeras delineate two discrete regions spanning the first through the third
      transmembrane domains (TM1-3) and TM10-11 that contribute to differences in their
      apparent affinities for DA, NE, and MPP+. These studies also suggest that TM2-3
      of the DA transporter have a role in selectively increasing the rate of DA uptake
      as compared with NE. TM4-8 of the DA transporter may influence the relative rate
      with which MPP+ is taken up into cells and could contribute to its selective
      toxicity in neurons expressing the DA transporter. These structure-function
      studies using chimeras of members of the superfamily of Na(+)- and Cl(-)
      dependent transporters provide a framework for identifying the specific
      structural or regulatory determinants contributing to substrate recognition and
      translocation by the DA and NE transporters.

PMID- 7809080
TI  - RAPT1, a mammalian homolog of yeast Tor, interacts with the FKBP12/rapamycin
      complex.
AB  - Rapamycin is a potent immunosuppressant that blocks the G1/S transition in
      antigen-activated T cells and in yeast. The similar effects of rapamycin in
      animal cells and yeast suggest that the biochemical steps affected by rapamycin
      are conserved. Using a two-hybrid system we isolated mammalian clones that
      interact with the human FK506/rapamycin-binding protein (FKBP12) in the presence
      of rapamycin. Specific interactors, designated RAPT1, encode overlapping
      sequences homologous to yeast Tor, a putative novel phosphatidylinositol 3
      kinase. A region of 133 amino acids of RAPT1 is sufficient for binding to the
      FKBP12/rapamycin complex. The corresponding region in yeast Tor contains the
      serine residue that when mutated to arginine confers resistance to rapamycin.
      Introduction of this mutation into RAPT1 abolishes its interaction with the
      FKBP12/rapamycin complex.

PMID- 7809083
TI  - Partially oxygenated sickled cells: sickle-shaped red cells found in circulating
      blood of patients with sickle cell disease.
AB  - A previously uncharacterized type of sickled cell was found in venous blood of
      patients with sickle cell disease when blood was collected without exposure to
      air and fixed immediately with 1% glutaraldehyde solution equilibrated with 5%
      oxygen. These cells were either elongated, resembling irreversibly sickled cells
      (ISCs), or nonelongated, with a raisin-like shape. Both types assumed a normal
      discoidal shape upon full oxygenation. Since these cells exist only under
      partially oxygenated conditions, they are described as partially oxygenated
      sickled cells (POSCs). POSCs are morphologically distinct from partially
      deoxygenated sickled cells formed during deoxygenation by having rounded edges,
      while the latter have sharp edges. Transmission electron microscopy of POSCs
      revealed various amounts of misaligned Hb S polymers. Investigations in vitro
      demonstrated the formation of POSC-like cells by partial oxygenation of
      deoxygenated cells. Since POSCs contain intracellular fibers and sickle readily
      upon deoxygenation, they may have clinical and pathological significance.

PMID- 7809084
TI  - The outer surface protein A of the spirochete Borrelia burgdorferi is a
      plasmin(ogen) receptor.
AB  - The spirochete Borrelia burgdorferi is the causative agent of Lyme borreliosis
      (Lyme disease) and is transmitted to mammalian hosts by tick vectors. In humans,
      the bacteria induce a complex disease, which involves the skin, joints, heart,
      and nervous system. However, the pathogenic principles of this multisystem
      illness are far from being understood. To disseminate from the site of the tick
      bite and invade multiple organ sites, spirochetes have to penetrate normal tissue
      barriers, such as vascular basement membranes and other organized extracellular
      matrices. Substantial evidence from other invasive bacterial infections suggest
      that spirochetes may use endogenous or host-derived enzymes--in particular,
      proteinases--for this purpose. Here we show that B. burgdorferi binds human
      plasmin(ogen)--mainly via its outer cell surface lipoprotein A. Binding of
      plasminogen to spirochetal receptor leads to an accelerated formation of active
      plasmin in the presence of host-derived plasminogen activator. The cell-surface
      associated plasmin cannot be regulated by the serum inhibitor alpha 2-antiplasmin
      and degrades high-molecular-weight glycoproteins, such as fibronectin. It is
      suggested that the acquisition of host-derived proteinase plasmin(ogen)
      contributes to the pathogenicity of B. burgdorferi.

PMID- 7809085
TI  - Regulation of neuronal Bcl2 protein expression and calcium homeostasis by
      transforming growth factor type beta confers wide-ranging protection on rat
      hippocampal neurons.
AB  - Excessive activation of glutamate receptors accompanied by Ca2+ overloading is
      thought to be responsible for the death of neurons in various conditions
      including stroke and epilepsy. Neurons also die if deprived of important growth
      factors and trophic influences, conditions sensitive to certain oncogene products
      such as the Bcl2 protein. We now demonstrate that transforming growth factor type
      beta (TGF-beta) prevents neuronal Ca2+ overloading of rat hippocampal neurons in
      response to the glutamatergic agonist N-methyl-D-aspartate or the Ca2+ ionophore
      4-Br-A23187 and, in addition, leads to a substantial increase in neuronal Bcl2
      protein expression. Parallel cytotoxicity experiments demonstrate that treatment
      with TGF-beta protects rat hippocampal neurons from death induced by
      excitotoxicity, trophic factor removal, and oxidative injury. Thus, TGF-beta may
      protect against a wide range of toxic insults by regulating two factors with
      great importance for neuronal viability.

PMID- 7809086
TI  - Identification of the guanine nucleotide dissociation stimulator for Ral as a
      putative effector molecule of R-ras, H-ras, K-ras, and Rap.
AB  - To identify proteins that bind to the Ras-related protein R-ras we performed a
      yeast two-hybrid cDNA library screen. Several clones were obtained encoding the C
      terminal region of the guanine nucleotide dissociation stimulator for Ral
      (RalGDS). The R-ras-binding domain of RalGDS (RalGDS-RBD) is distinct from the
      conserved catalytic exchange factor regions. Using the two-hybrid system, we show
      that RalGDS-RBD interacts with H-ras, K-ras, and Rap, and with active but not
      with inactive point mutants of these Ras-like GTPases. Moreover, using purified
      proteins, we demonstrate the direct GTP-dependent interaction of the Ras-like
      GTPases with RalGDS-RBD and full-length RalGDS in vitro. Furthermore, we show
      that RalGDS-RBD and the Ras-binding domain of Raf-1 compete for binding to the
      Ras-like GTPases. These data indicate that RalGDS is a putative effector molecule
      for R-ras, H-ras, K-ras, and Rap.

PMID- 7809087
TI  - Somatic mutation of immunoglobulin lambda chains: a segment of the major intron
      hypermutates as much as the complementarity-determining regions.
AB  - The rate and nature of hypermutation of immunoglobulin genes are of prime
      importance in the affinity maturation of antibodies. Although a considerable body
      of information has been gathered for kappa light chains, there is much less data
      for lambda chains. We have derived a large data base of somatic mutants of mouse
      lambda 1 light chains from Peyer's patches germinal center B cells. The
      endogenous lambda 1 genes mutate at a rate comparable to that previously found
      for a kappa transgene (V kappa ox1). There are intrinsic hot spots of mutation
      common to both in-frame and out-of-frame rearrangements; these hot spots cluster
      in hypermutating domains. In contrast to the pattern seen for V kappa Ox1, the
      hot spot clusters are found not only in complementarity-determining region (CDR)1
      but also in CDR2 and CDR3; mutations also cluster in the joining/constant region
      intron. The differences between the pattern of mutations in V kappa Ox1 and
      lambda 1 light chains are discussed.

PMID- 7809088
TI  - Synergistic binding of the Vibrio fischeri LuxR transcriptional activator domain
      and RNA polymerase to the lux promoter region.
AB  - LuxR, the Vibrio fischeri luminescence gene (lux) activator, is the best-studied
      member of a family of bacterial transcription factors required for cell density
      dependent expression of specific genes involved in associations with eukaryotic
      hosts. Neither LuxR nor any other LuxR homolog has been shown to bind DNA
      directly. We have purified the LuxR C-terminal transcriptional activator domain
      from extracts of recombinant Escherichia coli in which this polypeptide was
      expressed. The purified polypeptide by itself binds to lux regulatory DNA
      upstream of the lux box, a 20-bp palindrome that is required for LuxR activity in
      vivo, but it does not bind to the lux box. However, the LuxR C-terminal domain
      together with RNA polymerase protects a region including the lux box and the lux
      operon promoter from DNase I cleavage. There is very little protection of the lux
      operon promoter region from DNase I digestion in the presence of RNA polymerase
      alone. Apparently, there is a synergistic binding of the LuxR C-terminal domain
      and RNA polymerase to the promoter region. The upstream binding region for the
      purified polypeptide encompasses a binding site for cAMP receptor protein (CRP).
      Under some conditions, CRP binding can block the binding of the LuxR C-terminal
      domain to the upstream binding region, and it can also block the synergistic
      binding of the LuxR C-terminal domain and RNA polymerase to the lux box and
      luminescence gene promoter region. This description of DNA binding by the LuxR C
      terminal domain should lead to an understanding of the molecular interactions of
      the LuxR family of transcriptional activators with regulatory DNA.

PMID- 7809089
TI  - Growth-phase-dependent synthesis of histones in the archaeon Methanothermus
      fervidus.
AB  - Histone preparations from Methanothermus fervidus (HMf) contain two small
      polypeptides, HMfA and HMfB, which in solution are dimers and compact DNA to form
      nucleosome-like structures. These archaeal nucleosome-like structures constrain
      positive DNA supercoils, in contrast to the negatively supercoiled DNA in
      eukaryal nucleosomes. HMfA has been found to make up as much as 80% of HMf
      preparations synthesized by M. fervidus cells during the exponential growth phase
      of batch cultures but to decrease to approximately 50% as cultures enter the
      stationary phase. By using a nondenaturing polyacrylamide gel system at pH 6.1,
      we have demonstrated that HMf preparations contain HMfA homodimers, HMfB
      homodimers, and HMfA-HMfB heterodimers and that heating a mixture of recombinant
      HMfA and HMfB homodimers at 95 degrees C for 5 min generates HMfA-HMfB
      heterodimers. Circular dichroism spectroscopy indicates that HMfA and HMfB have
      very similar secondary structures, but based on agarose gel electrophoretic
      mobility shifts, DNA topology assays, and electron microscopy, they have
      different DNA binding properties. HMfA binding to DNA could be detected at lower
      protein/DNA ratios than HMfB, but HMfB binding resulted in more extensive DNA
      compaction. The increased HMfB synthesized in cells approaching the stationary
      phase and the highly compacted state of HMfB-bound DNA are consistent with
      preparations for the impending period of limited genome activity.

PMID- 7809090
TI  - Binding of Vav to Grb2 through dimerization of Src homology 3 domains.
AB  - The protooncogenic protein Vav has the structure of an intracellular signal
      transducer. It is exclusively expressed in cells of hematopoietic lineage and
      plays a crucial role in hematopoietic cell differentiation. Here we report that
      both in cell extracts and within intact mammalian cells Vav binds to Grb2 (Sem
      5/ASH/Drk), an adaptor molecule which plays a key role in Ras activation. The
      interaction became evident from a yeast two-hybrid screen and its specificity was
      demonstrated by in vitro binding assays. It is mediated by an unusual protein
      protein binding reaction: dimerization of specific intact Src homology 3 domains
      of each of the partners. Signaling during hematopoietic lineage differentiation
      may therefore involve the tissue-specific signal transducer Vav linking into the
      ubiquitous pathway involving Grb2 and ultimately Ras.

PMID- 7809091
TI  - Human T-cell leukemia virus type I Tax-protein-mediated activation of NF-kappa B
      from p100 (NF-kappa B2)-inhibited cytoplasmic reservoirs.
AB  - The human T-cell leukemia virus type I Tax protein transforms T cells through
      induced expression of many cellular genes, including those encoding the growth
      related proteins interleukin 2 and the alpha chain of its receptor. Induction of
      these genes is mediated, at least in part, through Tax-dependent
      posttranslational activation of NF-kappa B, typically heterodimers of p50 (NF
      kappa B1) and p65 (RelA). The preexisting NF-kappa B proteins are retained in the
      cytoplasm of cells by association with inhibitory ankyrin-motif-containing I
      kappa B proteins, primarily I kappa B-alpha but also including the precursor
      proteins p105 (NF-kappa B1) and p100 (NF-kappa B2). Here we demonstrate the
      existence of a previously undescribed multimeric cytoplasmic complex in which NF
      kappa B dimers are associated with the p100 inhibitor in a manner dependent on
      the precursor protein's ankyrin domain. We also demonstrate an antagonistic
      effect of the Tax protein on the cytoplasmic sequestration function of p100; this
      in turn leads to nuclear translocation of NF-kappa B dimers liberated from
      multimeric complexes. Tax may exert these effects through the physical
      association with p100. Tax also relieves the p100-mediated inhibition of DNA
      binding by p50-p65 heterodimers in vitro. The results demonstrate a mechanism by
      which Tax may activate NF-kappa B in T cells.

PMID- 7809092
TI  - Increased internal Ca2+ mediates neural induction in the amphibian embryo.
AB  - The molecular mechanism of neural induction is still unknown and the identity of
      the natural inducer remains elusive. It has been suggested that both the protein
      kinase C and cAMP signal transduction pathways may be involved in mediating its
      action. Here we provide evidence that Ca2+ is implicated in the process of
      transduction of the neuralizing signal. We find that an increase in intracellular
      Ca2+ concentration [Ca2+]i occurs during neural induction provoked in vitro by
      the lectin Con A in Pleurodeles waltl embryo. We demonstrate that specific L-type
      Ca2+ channel agonists also trigger neural induction. Conversely, noninducing
      lectins do not raise [Ca2+]i. Ryanodine and caffeine trigger neural induction. An
      increase in [Ca2+]i was also observed after treatment with the phorbol 12
      myristate 13-acetate, which has been reported to be inductive. The [Ca2+]i
      increase triggered by phorbol ester and Con A was abolished by staurosporine and
      by L-type Ca2+ channel antagonists. Our findings demonstrate that the [Ca2+]i
      increase occurs via L-type Ca2+ channels. We suggest an amplification of this
      increase by a Ca(2+)-induced Ca2+ release mechanism which involves intracellular
      ryanodine-sensitive stores. We propose that Ca(2+)-dependent processes controlled
      by protein kinase C are implicated in the regulation of gene expression in
      response to neural induction.

PMID- 7809093
TI  - Homeotic transformation of cervical vertebrae in Hoxa-4 mutant mice.
AB  - Hoxa-4 (previously known as Hox-1.4) is a mouse homeobox-containing gene that is
      expressed in the presumptive hindbrain and spinal cord, prevertebrae, and other
      tissues during embryogenesis. To understand the role of Hoxa-4 during
      development, we generated Hoxa-4 mutant mice. Homozygous mutants were viable and
      fertile. Analysis of neonatal skeletons revealed the development of ribs on the
      seventh cervical vertebra at variable penetrance and expressivity. A low
      frequency of alterations in sternal morphogenesis was also observed. In addition,
      we analyzed the skeletons of transgenic mice that overexpress Hoxa-4 and found
      that the formation of the small rib anlagen that often develop on the seventh
      cervical vertebra was suppressed. Analysis of adult homozygous mutant skeletons
      revealed that the dorsal process normally associated with the second cervical
      vertebra was also found on the third cervical vertebra. These results demonstrate
      that Hoxa-4 plays a role in conferring positional information along the
      anteroposterior axis to specify the identity of the third and the seventh
      cervical vertebrae.

PMID- 7809094
TI  - Tagged mutations at the Tox1 locus of Cochliobolus heterostrophus by restriction
      enzyme-mediated integration.
AB  - We have used the restriction enzyme-mediated integration insertional mutagenesis
      procedure to tag the Tox1 locus in the filamentous Ascomycete Cochliobolus
      heterostrophus. Mutations at other, unselected, loci were also identified and a
      high proportion (30-50%) of them were tagged. This procedure may be of general
      utility for simultaneously mutating and tagging genes in fungi and in other
      eukaryotes. The Tox1 locus of C. heterostrophus has been defined by Mendelian
      analysis as a single genetic element that controls production of T toxin, a
      linear polyketide involved in virulence of the fungus to its host plant, corn. To
      tag Tox1, protoplasts of a Tox1+ (T-toxin producing) strain were transformed with
      a linearized, nonhomologous plasmid along with an excess of the restriction
      enzyme used to linearize the plasmid. Of 1310 transformants recovered, two
      produced no detectable T toxin in culture or on corn plants. In each of these
      transformants, the Tox- mutation mapped at Tox1, was tagged with the selectable
      marker (hygB) on the transforming plasmid, and was tightly linked to the other
      tagged Tox- mutation. The two mutations, however, represent two different points
      of plasmid insertion at the Tox1 locus.

PMID- 7809095
TI  - Functional three-domain single-chain T-cell receptors.
AB  - T-cell receptors (TCRs) are membrane anchored heterodimers structurally related
      to antibody molecules. Single-chain antibodies can be engineered by linking the
      two variable domains, which fold properly by themselves. However, proper assembly
      of the variable domains of a human TCR (V alpha and V beta) that recognize the
      HLA-DR2b/myelin basic protein-(85-99) peptide complex was critically dependent on
      the addition of a third domain, the constant region of the TCR beta chain (C
      beta), to the single-chain construct. Single-chain molecules with the three
      domain design, but not those with the two-domain design, expressed in a
      eukaryotic cell as chimeric molecules linked either to glycosyl
      phosphatidylinositol or to the transmembrane/cytoplasmic domains of the CD3 zeta
      chain were recognized by a conformation-sensitive monoclonal antibody. The
      chimeric three-domain single-chain TCR linked to CD3 zeta chain signaled in
      response to both the specific HLA-DR/peptide and the HLA-DR/superantigen
      staphylococcal enterotoxin B complexes. Thus, by using this three-domain design,
      functional single-chain TCR molecules were expressed with high efficiency. The
      lipid-linked single-chain TCR was solubilized by enzymatic cleavage and purified
      by affinity chromatography. The apparent requirement of the constant domain for
      cooperative folding of the two TCR variable domains may reflect significant
      structural differences between TCR and antibody molecules.

PMID- 7809096
TI  - Interleukin 12 induces the differentiation of major histocompatibility complex
      class I-primed cytotoxic T-lymphocyte precursors into allospecific cytotoxic
      effectors.
AB  - The production of interleukin 12 (IL-12) following allogeneic stimulation and its
      involvement in the differentiation of allospecific cytotoxic T lymphocytes (CTLs)
      have been investigated. Supernatants of mixed lymphocyte cultures had detectable
      levels of IL-12 p40 which were completely abrogated after depletion of responder
      cells from monocytes. While addition to the culture of anti-IL-12 neutralizing
      antibodies partially inhibited the allogeneic proliferative response and the
      subsequent CTL activity, addition of IL-12 stimulated both responses, suggesting
      that endogenously produced IL-12 plays a role in the development of
      alloreactivity. Furthermore, using primary mixed cultures of lymphocytes from
      major histocompatibility complex-recombinant siblings identical for class II
      antigens and displaying class I disparity, we demonstrated that addition of
      recombinant IL-12 at the sensitizing phase of the primary mixed lymphocyte
      culture induced CTL activity. Under these stimulation conditions, addition of
      recombinant IL-12 also triggered cell proliferation, indicating that IL-12
      provides both growth and differentiation signals. The mechanism underlying this
      process does not appear to require IL-2, since IL-12-mediated CTL generation was
      not abrogated by anti-IL-2 alpha-chain antibodies. IL-12 increased granzyme B and
      perforin mRNA accumulation in major histocompatibility complex class I-primed
      lymphocytes, suggesting that this cytokine activates these two genes in CTL
      precursors. We conclude that IL-12 can stimulate the generation of alloreactive
      CTLs. We suggest that IL-12 may play a role in helper cell-independent CTL
      generation.

PMID- 7809097
TI  - Potent bombesin antagonists with C-terminal Leu-psi(CH2-N)-Tac-NH2 or its
      derivatives.
AB  - Various pseudononapeptide bombesin (BN)-(6-14) antagonists with a reduced peptide
      bond (CH2-NH) between positions 13 and 14 can suppress the mitogenic activity of
      BN or gastrin-releasing peptide in 3T3 fibroblast cells and small cell lung
      carcinoma. In the search for more potent BN antagonists, 10 modified nonapeptide
      BN antagonists containing N-terminal D-Phe, D-Cpa, and D- or L-Tpi and C-terminal
      Leu-psi(CH2-N)-Tac-NH2, Leu-psi(CH2-N)-MeTac-NH2, or Leu-psi(CH2-N)-Me2Tac-NH2
      have been synthesized by incubating [13 psi 14,CH2-NH,Cys14]BN-(6-14) or [13 psi
      14-CH2-NH,Pen14]BN-(6-14) with formaldehyde or acetaldehyde (Cpa = 4
      chlorophenylalanine, Tac = thiazolidine-4-carboxylic acid, Tpi = 2,3,4,9
      tetrahydro-1H- pyrido[3,4-b]indol-3-carboxylic acid, and Pen = penicillamine).
      The biological activities of these compounds were then evaluated. [D-Phe6,13 psi
      14,CH2-N,Tac14]BN-(6-14) (RC-3950-II) and [D-Phe6,13 psi 14,CH2-N,Me2Tac14]BN-(6
      14) (RC-3985-II) exhibited greater potency in inhibition of 125I-labeled [Tyr4]BN
      binding to Swiss 3T3 cells than their parent compounds [D-Phe6,13 psi 14,CH2
      NH,Cys14]BN-(6-14) (RC-3950-I) and [D-Phe6,13 psi 14,CH2-NH,Pen14]BN-(6-14) (RC
      3985-I). The order of binding affinities of these compounds was as follows: [13
      psi 14,CH2-N,Tac14]BN-(6-14) > [13 psi 14,CH2-N,Me2Tac14]BN-(6-14) > [13 psi
      14,CH2-N,MeTac14]BN-(6-14). In most cases, the analogs with C-terminal Leu
      psi(CH2-N)-Tac-NH2 were also more potent growth inhibitors of 3T3 cells than
      compounds containing C-terminal Leu-psi(CH2-N)-Me2Tac-NH2 or Leu-psi(CH2-N)-MeTac
      NH2. The best BN antagonists of this series, RC-3950-II and [D-Cpa6,13 psi 14,CH2
      N,Tac14]BN- (6-14) (RC-3925-II), inhibited gastrin-releasing peptide-stimulated
      growth of Swiss 3T3 cells with IC50 values of 1 nM and 6 nM, respectively. Since
      antagonists of this class inhibit growth of various tumors in animal cancer
      models, some of them may have clinical applications.

PMID- 7809099
TI  - An increase in dendritic spine density on hippocampal CA1 pyramidal cells
      following spatial learning in adult rats suggests the formation of new synapses.
AB  - The search for cellular correlates of learning is a major challenge in
      neurobiology. The hippocampal formation is important for learning spatial
      relations. A possible long-lasting consequence of such spatial learning is
      alteration of the size, shape, or number of excitatory synapses. The dendritic
      spine density is a good index for the number of hippocampal excitatory synapses.
      By using laser-scanning confocal microscopy, we observed a significantly
      increased spine density in CA1 basal dendrites of spatially trained rats when
      compared to nontrained controls. With unchanged dendritic length, the higher
      spine density reflects an increased number of excitatory synapses per neuron
      associated with spatial learning.

PMID- 7809098
TI  - Exposure of human ovarian carcinoma to cisplatin transiently sensitizes the tumor
      cells for liposome-mediated gene transfer.
AB  - Human ovarian carcinoma cells (line 2008) grown as subcutaneous solid tumor in
      the severe combined immunodeficient mouse can be transfected by directly
      injecting a plasmid DNA-liposome complex into the tumor (in situ lipofection).
      The level of reporter gene expression in the tumor cells was significantly
      elevated if the animal received a single i.p. injection of cisplatin 1 week
      before the lipofection. Sensitization of the tumor for lipofection peaked 1 week
      after cisplatin injection and declined thereafter. Cells exposed to low
      concentration of cisplatin in vitro for four to five doubling times also showed
      elevated sensitivity for lipofection in vitro. Cisplatin was the only anticancer
      drug tested that exhibited this activity. These results suggest a sequential
      combinational gene therapy protocol with cisplatin for the ovarian carcinoma.

PMID- 7809100
TI  - Propensity for a leucine zipper-like domain of human immunodeficiency virus type
      1 gp41 to form oligomers correlates with a role in virus-induced fusion rather
      than assembly of the glycoprotein complex.
AB  - For a number of viruses, oligomerization is a critical component of envelope
      processing and surface expression. Previously, we reported that a synthetic
      peptide (DP-107) corresponding to the putative leucine zipper region (aa 553-590)
      of the transmembrane protein (gp41) of human immunodeficiency virus type 1 (HIV
      1) exhibited alpha-helical secondary structure and self-associated as a coiled
      coil. In view of the tendency of this type of structure to mediate protein
      association, we speculated that this region of gp41 might play a role in HIV-1
      envelope oligomerization. However, later it was shown that mutations which should
      disrupt the structural elements of this region of gp41 did not affect envelope
      processing, transport, or surface expression (assembly oligomerization). In this
      report we compare the effects of amino acid substitutions within this coiled-coil
      region on structure and function of both viral envelope proteins and the
      corresponding synthetic peptides. Our results establish a correlation between the
      destabilizing effects of amino acid substitutions on coiled-coil structure in the
      peptide model and phenotype of virus entry. These biological and physical
      biochemical studies do not support a role for the coiled-coil structure in
      mediating the assembly oligomerization of HIV-1 envelope but do imply that this
      region of gp41 plays a key role in the sequence of events associated with viral
      entry. We propose a functional role for the coiled-coil domain of HIV-1 gp41.

PMID- 7809101
TI  - A Drosophila protein homologous to the human p70 Ku autoimmune antigen interacts
      with the P transposable element inverted repeats.
AB  - P transposable elements in Drosophila are mobilized via a cut-and-paste
      mechanism. This mode of transposition requires repair of both a double-strand
      break at the donor DNA site and gapped DNA at the target site. Biochemical
      studies have identified a cellular non-P element-encoded DNA binding protein,
      termed the inverted repeat binding protein (IRBP), that specifically interacts
      with the outer half of the 31-bp terminal inverted repeats. Protein sequence
      information was used to isolate cDNA clones encoding IRBP. Sequence analysis
      shows that IRBP is related to the 70-kDa subunit of the human Ku autoimmune
      antigen. The mammalian Ku antigen binds free DNA termini and has been implicated
      in immunoglobulin VDJ recombination, DNA repair, and transcription. In addition,
      Ku is the DNA binding subunit of the double-strand DNA-dependent protein kinase.
      Cytogenetic mapping indicates that the IRBP gene maps to chromosomal position 86E
      on the right arm of the third chromosome.

PMID- 7809102
TI  - Scallop striated and smooth muscle myosin heavy-chain isoforms are produced by
      alternative RNA splicing from a single gene.
AB  - We report here that the catch and striated adductor muscle myosin heavy-chain
      (MHC) isoforms of scallop (Argopecten irradians, previously Aequipecten
      irradians) are generated by alternative RNA splicing from a single gene. Scallop
      catch muscle cDNA and genomic DNA were amplified by PCR using primers based on
      the previously sequenced scallop striated muscle MHC cDNA. Mapping of the
      exon/intron borders and sequencing of a full-length catch muscle MHC in
      overlapping fragments revealed that the 24-kb gene encodes the MHC polypeptide in
      27 exons and that four sets of tandem exon pairs are alternatively spliced into a
      striated and a catch MHC isoform. An additional alternative exon was identified
      in catch cDNA and is apparently spliced into a minor MHC isoform. The striated
      muscle-specific isoform is not expressed in other tissues, whereas the catch-type
      isoforms were also detected in various smooth muscles, but not in the striated
      one. Of the alternative exons, exons 5 and 6 encode part of the ATP-binding
      region and the 25-kDa/50-kDa proteolytic junction; exon 13 encodes part of one of
      the actin-binding regions and extends to the active site; exon 20 encodes the
      middle of the rod hinge region; exon 26 in the striated-specific sequence starts
      with the stop codon, whereas the catch-specific exon codes for an additional 10
      residues. Differences between the alternative exons presumably determine the
      lower ATPase activity of smooth muscle myosin, contribute to the different
      structure of the striated and smooth muscle thick filaments, and may also be
      important for the molecular mechanism of the catch phenomenon.

PMID- 7809103
TI  - Phosphorylation negatively regulates the function of coactivator PC4.
AB  - Human positive cofactor 4 (PC4) mediates activator-dependent transcription by RNA
      polymerase II, apparently through interactions with transcriptional activators
      and the basal transcription machinery. We report here that PC4 function is
      modulated by in vivo phosphorylation. Protein-protein interaction studies and in
      vitro transcription assays demonstrate that only the nonphosphorylated form of
      PC4 is functionally active. Although recombinant PC4 can be phosphorylated by
      casein kinase II and protein kinase C in vitro, mutational and mass spectrometric
      analyses suggest that the in vivo hyperphosphorylation of PC4 is mediated mainly
      by casein kinase II and restricted to an N-terminal serine-rich region. These
      observations provide one example of a transcriptional cofactor that is negatively
      regulated by casein kinase II phosphorylation.

PMID- 7809104
TI  - Allele-specific quantification of Drosophila engrailed and invected transcripts.
AB  - Changes in levels of transcription can be difficult to gauge in animals with
      lethal mutations. For example, mutations in a regulatory region of an essential
      gene can have secondary consequences that complicate attempts to quantify the
      transcripts produced by the mutant gene. We describe a method that circumvents
      this problem by revealing the relative amount of transcript produced from each
      allele in a heterozygote. With this method, recessive lethal mutations can be
      analyzed in animals that are phenotypically wild type. We used this technique to
      analyze mutations in the regulatory region of the Drosophila engrailed gene and
      found that truncations reduce transcription to levels that depend both upon the
      tissue and upon the location of the chromosomal break. We also found that these
      mutations affect expression of the linked invected gene, suggesting that
      engrailed and invected share a complex set of regulatory elements that operate
      over at least 85 kb. We suggest that this technique will have general utility for
      the quantitation of allele-specific transcripts, even when amounts of tissue are
      limiting.

PMID- 7809105
TI  - Coherent nuclear dynamics at room temperature in bacterial reaction centers.
AB  - A room-temperature study is reported of the femtosecond spectral evolution of the
      stimulated emission band of the primary electron-transfer precursor P* in
      bacterial photosynthesis. The study was performed with membranes of the antenna
      deficient RCO1 mutant of Rhodobacter sphaeroides. A time-dependent red shift,
      reflecting nuclear motion out of the Franck-Condon region of the excited state,
      is resolved. Analysis of oscillatory features persisting for > 1 ps in the
      kinetics revealed main frequencies of the activated motions at 30, 84, 145, and
      192 cm-1. The oscillations occur on the time scale of primary electron transfer.
      Our results set a lower limit for the vibrational dephasing time in P* that is
      not compatible with the usual assumption in theoretical treatments of complete
      vibrational relaxation prior to electron transfer, even at room temperature.

PMID- 7809106
TI  - Direct evidence that Gi-coupled receptor stimulation of mitogen-activated protein
      kinase is mediated by G beta gamma activation of p21ras.
AB  - Stimulation of Gi-coupled receptors leads to the activation of mitogen-activated
      protein kinases (MAP kinases). In several cell types, this appears to be
      dependent on the activation of p21ras (Ras). Which G-protein subunit(s) (G alpha
      or the G beta gamma complex) primarily is responsible for triggering this
      signaling pathway, however, is unclear. We have demonstrated previously that the
      carboxyl terminus of the beta-adrenergic receptor kinase, containing its G beta
      gamma-binding domain, is a cellular G beta gamma antagonist capable of
      specifically distinguishing G alpha- and G beta gamma-mediated processes. Using
      this G beta gamma inhibitor, we studied Ras and MAP kinase activation through
      endogenous Gi-coupled receptors in Rat-1 fibroblasts and through receptors
      expressed by transiently transfected COS-7 cells. We report here that both Ras
      and MAP kinase activation in response to lysophosphatidic acid is markedly
      attenuated in Rat-1 cells stably transfected with a plasmid encoding this G beta
      gamma antagonist. Likewise in COS-7 cells transfected with plasmids encoding Gi
      coupled receptors (alpha 2-adrenergic and M2 muscarinic), the activation of Ras
      and MAP kinase was significantly reduced in the presence of the coexpressed G
      beta gamma antagonist. Ras-MAP kinase activation mediated through a Gq-coupled
      receptor (alpha 1-adrenergic) or the tyrosine kinase epidermal growth factor
      receptor was unaltered by this G beta gamma antagonist. These results identify G
      beta gamma as the primary mediator of Ras activation and subsequent signaling via
      MAP kinase in response to stimulation of Gi-coupled receptors.

PMID- 7809107
TI  - Transcriptional induction of Ty recombination in yeast.
AB  - Families of repeated sequences are present in the genomes of all eukaryotes.
      Little is known about the mechanism(s) that prevents recombination between
      repeated sequences. In the yeast Saccharomyces cerevisiae, recombination between
      homologous sequences placed at nonhomologous locations in the genome (ectopic
      recombination) has been shown to occur at high frequencies for artificially
      created repeats, but at relatively low frequencies for a natural family of
      repeated sequences, the Ty family. We have previously shown that a high level of
      Ty cDNA in the cell causes an increase in the rate of nonreciprocal recombination
      (gene conversion) of a marked Ty element. In the present study, we show that it
      is also possible to elevate the rate of recombination of a marked Ty by
      increasing its transcription. This induction is different from, and acts
      synergistically to, the one seen upon increased levels of donor Ty cDNA. We show
      that the induction by transcription does not require the products of the RAD50,
      RAD51, and RAD57 genes. In contrast, cDNA-mediated recombination is dependent on
      the product of the RAD51 gene but not on products of the genes RAD50 or RAD57.

PMID- 7809108
TI  - Characteristics of peptide and major histocompatibility complex class I/beta 2
      microglobulin binding to the transporters associated with antigen processing
      (TAP1 and TAP2).
AB  - The transporter proteins associated with antigen processing (TAP proteins)
      transport antigenic peptides across the endoplasmic reticulum membrane where they
      can assemble with newly synthesized major histocompatibility complex (MHC) class
      I/beta 2-microglobulin (beta 2m) dimers. We have shown previously that TAP
      possesses a peptide-recognition site with broad specificity and that MHC class
      I/beta 2m dimers physically associate with TAP. Here, we further characterize the
      nature of the peptide-binding site on TAP, and the site of interaction of TAP
      with MHC class I/beta 2m dimers. TAP photoaffinity labeling experiments revealed
      that both TAP1 and TAP2 are photolabeled by two distinct photopeptide analogues,
      suggesting that elements of both TAP1 and TAP2 compose the peptide-recognition
      site. TAP photolabeling analysis on transfectant cell lines that express TAP1 and
      TAP2 both individually and together revealed that efficient formation of the
      peptide-binding site occurs only when TAP1 and TAP2 are coexpressed, which
      correlates with the finding that peptide translocation via TAP occurs only in the
      presence of both TAP1 and TAP2. These data strongly support the notion that TAP
      functions as a heterodimer. MHC class I/beta 2m dimers were shown to associate
      with individual TAP1 chains but were not detectable with individual TAP2 chains.
      This result suggests that the site of interaction for MHC class I/beta 2m dimers
      with TAP is on TAP1.

PMID- 7809109
TI  - Molecular evidence for two forms of Crohn disease.
AB  - Recent epidemiological evidence suggests that there are two forms of Crohn
      disease (CD): perforating and nonperforating. We hypothesized that, just as with
      tuberculoid and lepromatous leprosy, differences in the two forms of CD would be
      both identified and determined by differences in the host immune response.
      Resected intestinal tissue from control patients as well as perforating and
      nonperforating CD patients was evaluated for mRNA levels. We employed 32P PCR
      amplification with published or custom-designed primers of a housekeeping gene
      (beta-actin); a human T-cell marker (CD3-delta); and the cytokines tumor necrosis
      factor alpha, transforming growth factor beta, granulocyte/macrophage colony
      stimulating factor, interleukin (IL) 1 beta, IL-1ra, and IL-6. Differences were
      identified with IL-1 beta (control = 162 +/- 57 vs. perforating = 464 +/- 154 vs.
      nonperforating = 12,582 +/- 4733; P < or = 0.02) and IL-1ra (control = 1337 +/-
      622 vs. perforating = 2194 +/- 775 vs. nonperforating = 9715 +/- 2988; P < or =
      0.02). These data corroborate the epidemiological observation that there are two
      forms of CD. Nonperforating CD, the more benign form, is associated with
      increased IL-1 beta and IL-1ra mRNA expression. We conclude that it is the host
      immune response that determines which form of CD becomes manifest in any given
      individual and discuss the investigative, diagnostic, and therapeutic
      implications of these observations.

PMID- 7809110
TI  - Cationic modulation of rho 1-type gamma-aminobutyrate receptors expressed in
      Xenopus oocytes.
AB  - A study was made of the effects of di- and trivalent cations on homomeric rho 1
      type gamma-aminobutyrate (GABA rho 1) receptors expressed in Xenopus oocytes
      after injection of mRNA coding for the GABA rho 1 subunit. GABA elicited large
      currents with a Kd approximately 1 microM. The properties of these GABA rho 1
      receptors were similar to those of native bicuculline-resistant GABA receptors
      expressed by retinal mRNA. GABA rho 1 currents showed very little
      desensitization, were blocked by picrotoxin but not by bicuculline, and were not
      modulated by barbiturates, benzodiazepines, or beta-carbolines. Zn2+ reversibly
      decreased GABA rho 1 responses (IC50 = 22 microM). Other divalent cations were
      also tested and their rank order of potency was: Zn2+ approximately Ni2+
      approximately Cu2+ >> Cd2+, whereas Ba2+, Co2+, Sr2+, Mn2+, Mg2+, and Ca2+ showed
      little or no effect. In contrast, La3+ reversibly potentiated the GABA currents
      mediated by homomeric GABA rho 1 receptors, with an EC50 = 135 microM and a
      maximal potentiation of about 100% (GABA, 1 microM; La3+, 1 mM). Other
      lanthanides showed similar effects (Lu3+ > Eu3+ > Tb3+ > Gd3+ > Er3% > Nd3+ >
      La3+ > Ce3+). Thus, GABA rho 1 receptors contain sites for cationic recognition,
      and in particular, Zn2+ may play a role during synaptic transmission in the
      retina.

PMID- 7809111
TI  - Polylysine domain of K-ras 4B protein is crucial for malignant transformation.
AB  - Previous studies have shown that posttranslational modifications are required for
      both oncogenic K-ras 4B protein membrane binding and transforming activity. In
      addition, Hancock et al. [Hancock, J. F., Patterson, H. & Marshall, C. J. (1990)
      Cell 63, 133-139] found that a polylysine domain contained at the C terminus of K
      ras 4B was also absolutely essential for K-ras 4B membrane binding but,
      surprisingly, neither the polylysine domain nor membrane binding was required for
      transforming activity. We have performed similar studies, but our results are
      distinctly different. Our studies indicate that the polylysine domain is crucial
      for K-ras 4B transforming activity. Moreover, we demonstrate that although the
      polylysine domain increases K-ras 4B membrane binding, significant amounts of
      membrane binding can occur in the absence of this domain. Finally, while our
      studies are consistent with the notion that membrane binding is required for K
      ras 4B transforming activity, we show that membrane binding, in and of itself, is
      not sufficient for efficient K-ras 4B transforming activity.

PMID- 7809112
TI  - Identification of the apparent carrier in mycolic acid synthesis.
AB  - The mycolic acids are large (C70-90) alpha-alkyl, beta-hydroxy fatty acids and
      are the major determinants of the mycobacterial cell wall's impermeable barrier.
      The biosynthesis of mycolic acids is barely understood (they are probably the
      products of specialized elongation and Claisen-type condensation), and yet their
      synthesis is the site of action of several mainline antituberculosis drugs. We
      describe the isolation from Mycobacterium smegmatis and the full characterization
      of a 6-O-mycolyl-beta-D-mannopyranosyl-1-monophosphoryl-3,7,11,15,19,23 ,27-
      heptamethyl-(2Z,6E,10E)-octacosatrien-1-ol . The identification of a mycolyl
      mannosylphosphopolyprenol supported by cell-free labeling experiments and earlier
      literature suggests unusual biochemical pathways in which mature mycolic acids
      are formed from beta-oxo precursors while attached to a mannosyl-P-polyprenol, in
      which form they are transported through the membrane prior to final deposition as
      arabinan-bound mycolates.

PMID- 7809113
TI  - Tumor necrosis factor alpha-induced phosphorylation of I kappa B alpha is a
      signal for its degradation but not dissociation from NF-kappa B.
AB  - Activation of the NF-kappa B/Rel family of transcription factors is regulated by
      a cytoplasmic inhibitor, I kappa B alpha. Activity of I kappa B alpha is in turn
      modulated by phosphorylation and proteolysis. It has been postulated that
      phosphorylation of I kappa B alpha leads to its dissociation from NF-kappa B, and
      free I kappa B alpha is targeted for rapid degradation. However, this
      phosphorylation-mediated dissociation event has not been demonstrated in vivo. We
      demonstrate that, contrary to this hypothesis, phosphorylation of I kappa B alpha
      induced by tumor necrosis factor alpha in HeLa cells does not induce
      dissociation. We propose a model in which (i) induced phosphorylation of I kappa
      B alpha does not result in its dissociation from NF-kappa B, (ii) phosphorylation
      of I kappa B alpha serves as a signal for degradation, and (iii) degradation of I
      kappa B alpha occurs while it is still complexed with NF-kappa B.

PMID- 7809114
TI  - Pax-3 contains domains for transcription activation and transcription inhibition.
AB  - Pax-3 is a member of the Pax family of transcription factors involved in
      transcriptional control events during embryonic development. Here we report a
      functional dissection of the Pax-3 protein and describe the protein domains which
      are responsible for different activities. A transcription inhibition activity is
      located in the first 90 N-terminal amino acids and includes part of the paired
      domain. Furthermore, the C terminus of Pax-3 is able to confer transcriptional
      activation of basal promoters. Pax-3 can utilize both transcription modulating
      functions and activates transcription over a narrow range of protein
      concentration in the presence of promoter elements containing functional binding
      sites.

PMID- 7809116
TI  - Hematopoietic development of vav-/- mouse embryonic stem cells.
AB  - The vav protooncogene product is expressed nearly exclusively in hematopoietic
      lineages and contains several structural motifs (SH2/SH3 domains and a dbl
      oncogene homology region) typical of proteins functioning in signaling pathways.
      To ascertain if vav expression is required for hematopoiesis we generated vav
      negative mouse embryonic stem cells by gene targeting and examined the
      consequences of loss of vav function on erythroid and myeloid development in
      vitro and in vivo. In conflict with the conclusions drawn from expression of
      antisense vav RNA in embryonic stem cells [Wulf, G. M., Adra, C. N. & Lim, B.
      (1993) EMBO J. 12, 5065-5074], we observed erythroid and myeloid development in
      the absence of vav. These experiments demonstrate that vav expression is not
      absolutely required for hematopoietic development.

PMID- 7809115
TI  - A distinct class of intracellular storage vesicles, identified by expression of
      the glucose transporter GLUT4.
AB  - Some cell types have cytoplasmic storage vesicles whose fusion with the cell
      surface is triggered by an extracellular signal. To explore the relationship
      between different classes of storage vesicles, we expressed, in the neuro
      endocrine cell line PC12, the facilitative glucose transporter GLUT4, which is
      stored in small cytoplasmic vesicles in fat and muscle cells and mobilized to the
      cell surface when insulin is present. PC12 cells have two known types of storage
      vesicles, secretory granules and synaptic vesicles, but GLUT4 is targeted to
      neither. It is recovered, however, in a class of small vesicles that sediment
      approximately twice as fast as synaptic vesicles. Immunoelectron microscopy
      confirmed the presence of such small vesicles in transfected PC12 cells. By
      velocity sedimentation analysis, GLUT4 vesicles efficiently exclude the synaptic
      vesicle markers synaptophysin, SV2, and synaptobrevin; the transferrin receptor,
      a marker of conventional endocytosis; and the polymeric immunoglobulin receptor,
      a marker of transcytosis. The exclusion of synaptophysin and the transferrin
      receptor from most of the GLUT4-containing structures was confirmed by confocal
      immunofluorescence microscopy. Like synaptic vesicles, therefore, GLUT4 vesicles
      of PC12 cells appear to be a unique type of organelle. A GLUT4-containing
      organelle of identical sedimentation properties was found in transfected
      fibroblast cell lines and in rat adipocytes. On stimulation of the adipocytes
      with insulin, GLUT4 was translocated from the peak of small vesicles to faster
      sedimenting membranes. We propose that the class of vesicles described here is
      present in a wide range of cell types and is involved in transient modification
      of the cell surface.

PMID- 7809117
TI  - Targeting of the polyhydroxybutyrate biosynthetic pathway to the plastids of
      Arabidopsis thaliana results in high levels of polymer accumulation.
AB  - In the bacterium Alcaligenes eutrophus, three genes encode the enzymes necessary
      to catalyze the synthesis of poly[(R)-(-)-3-hydroxybutyrate] (PHB) from acetyl
      CoA. In order to target these enzymes into the plastids of higher plants, the
      genes were modified by addition of DNA fragments encoding a pea chloroplast
      transit peptide, a constitutive plant promoter, and a poly(A) addition sequence.
      Each of the modified bacterial genes was introduced into Arabidopsis thaliana by
      Agrobacterium-mediated transformation, and plants containing all three genes were
      obtained by sexual crosses. These plants accumulated PHB up to 14% of the dry
      weight as 0.2- to 0.7-micron granules within plastids. In contrast to earlier
      experiments in which expression of the PHB biosynthetic pathway in the cytoplasm
      led to a deleterious effect on growth, expression of the PHB biosynthetic pathway
      in plastids had no obvious effect on the growth or fertility of the transgenic
      plants and resulted in a 100-fold increase in the amount of PHB that accumulated.
      We conclude that there does not appear to be any biological barrier to high-level
      production of PHB in higher plants. The high level of PHB accumulation also
      suggests that the synthesis of plastid acetyl-CoA is regulated by a mechanism
      which responds to metabolic demand.

PMID- 7809118
TI  - Time course of Ca2+ concentration triggering exocytosis in neuroendocrine cells.
AB  - We have used the secretory response of chromaffin cells to estimate the
      submembrane intracellular Ca2+ concentration ([Ca2+]i) "seen" by secretory
      granules during short depolarizations. The rate of secretion during a
      depolarization was assessed by combining the electrochemical method of
      amperometry and electrical capacitance measurements. The rate was then related to
      [Ca2+]i based on a previous characterization of how Ca2+ affects the dynamics of
      vesicle priming and fusion in chromaffin cells [Heinemann, C., Chow, R. H.,
      Neher, E. & Zucker, R. S. (1994) Biophys. J. 67, in press]. Calculated [Ca2+]i
      rose during the depolarization to a peak of < 10 microM, then decayed over tens
      of milliseconds. In synapses, vesicles are presumed to be located within
      nanometers of Ca2+ channels where [Ca2+]i is believed to rise in only
      microseconds to near steady-state levels of hundreds of micromolar. Channel
      closure should lead to a decrease in [Ca2+]i also in microseconds. Our findings
      of the slower time course and the lower peak [Ca2+]i suggest that in chromaffin
      cells, unlike synapses, Ca2+ channels and vesicles are not strictly colocalized.
      This idea is consistent with previously published data on dense-core vesicle
      secretion from diverse cell types.

PMID- 7809119
TI  - Identification of calreticulin as a rubella virus RNA binding protein.
AB  - Previously, we observed that sequences at the 3' end of rubella virus (RV)
      genomic RNA that form a stable stem-loop structure are necessary for initiation
      of RNA replication. A cytosolic protein found in Vero 76 cells (simian origin)
      specifically bound to the 3' (+)-stem-loop sequence. In the present study, we
      have purified the RNA binding protein and identified it as a simian homologue of
      human calreticulin. The purified calreticulin binds to the RV RNA with
      specificity similar to the protein present in cytosolic extracts. Human
      calreticulin antibodies recognize several forms of simian calreticulin, one of
      which is phosphorylated in vivo. A 2-fold increase in phosphorylation of this
      form of calreticulin is observed in RV-infected cells. Recombinant human
      calreticulin can bind RV 3' (+)-stem-loop RNA only after undergoing in vitro
      phosphorylation. This binding activity is abrogated by pretreatment of
      phosphorylated recombinant human calreticulin with alkaline phosphatase. The RV
      RNA was also immunoprecipitated from RV-infected UV-crosslinked Vero 76 cells by
      using calreticulin antibodies. Our results show that phosphorylated calreticulin
      is an RNA binding protein and phosphorylation is necessary for this activity.
      Specific binding of calreticulin to the cis-acting element of RV RNA in vivo
      suggests a possible role for this interaction in viral replication.

PMID- 7809120
TI  - Molecular cloning and derived primary structure of cobra venom factor.
AB  - Cobra venom factor (CVF) is the complement-activating protein in cobra venom.
      Like C3b, CVF forms with factor B and factor D in human and mammalian serum the
      bimolecular C3/C5 convertase. This functional similarity of CVF and C3 correlates
      with many structural similarities, which led to the suggestion that CVF is
      evolutionally related to C3. We report here the molecular cloning and derived
      primary structure of CVF. CVF mRNA is > 5924 nucleotides in length. It contains a
      single open reading frame of 4926 nucleotides, coding for a pre-pro-protein of
      1642 amino acids. The deduced amino acid sequence reveals approximately 70%
      protein similarity to mammalian and human C3 and exceeds 91% in the case of cobra
      C3. The single-chain pre-pro-CVF consists of a 22-amino acid signal sequence, a
      627-amino acid alpha-chain, and a 989-amino acid precursor chain for the CVF
      gamma- and beta-chains. The processing of pro-CVF involves the removal of 4
      arginine residues between the alpha- and precursor chains as well as of the C3a
      like and C3d-like domains from the precursor chain, thereby confirming the
      predicted chain homologies to C3. Pro-CVF contains five potential N-glycosylation
      sites, of which only three can be expected to be glycosylated in mature CVF. Like
      C3, pro-CVF contains 27 cysteine residues and a homologous thioester site in the
      C3d-like region.

PMID- 7809122
TI  - Biosynthesis of a defensive insect alkaloid: epilachnene from oleic acid and
      serine.
AB  - The biosynthesis of the azamacrolide epilachnene by the coccinellid beetle
      Epilachna varivestis has been studied with 2H-labeled oleic acid, 2H-labeled L
      serine, and 13C,15N-labeled L-serine. The incorporation of these precursors into
      epilachnene defines the origin of the alkaloid's entire carbon/nitrogen skeleton.
      GC/MS and GC/IR studies of alkaloid produced by Epilachna fed with deuteriated
      oleic acid show that oleic acid loses four carbon atoms from its carboxyl end
      during the biosynthesis. Other details, including the mechanism of carbon
      nitrogen bond formation between the fatty acid and amino acid moieties, remain to
      be established.

PMID- 7809121
TI  - Sodium channel mutations in paramyotonia congenita exhibit similar biophysical
      phenotypes in vitro.
AB  - Mutations in the skeletal muscle voltage-gated Na+ channel alpha-subunit have
      been found in patients with two distinct hereditary disorders of sarcolemmal
      excitation: hyperkalemic periodic paralysis (HYPP) and paramyotonia congenita
      (PC). Six of these mutations have been functionally expressed in a heterologous
      cell line (tsA201 cells) using the recombinant human skeletal muscle Na+ channel
      alpha-subunit cDNA hSkM1. PC mutants from diverse locations in this subunit
      (T1313M, L1433R, R1448H, R1448C, A1156T) all exhibit a similar disturbance in
      channel inactivation characterized by reduced macroscopic rate, accelerated
      recovery, and altered voltage dependence. PC mutants had no significant
      abnormality in activation. In contrast, one HYPP mutation studied (T704M) has a
      normal inactivation rate but exhibits shifts in the midpoints of steady-state
      activation and inactivation along the voltage axis. These findings help to
      explain the phenotypic differences between HYPP and PC at the molecular and
      biophysical level and contribute to our understanding of Na+ channel structure
      and function.

PMID- 7809123
TI  - The tsA58 simian virus 40 large tumor antigen disrupts megakaryocyte
      differentiation in transgenic mice.
AB  - Thrombocytopenia is a condition of multiple etiologies affecting the
      megakaryocyte lineage. To perturb this lineage in transgenic mice, the tsA58
      mutation of the simian virus 40 large tumor antigen was targeted to
      megakaryocytes using the platelet factor 4 promoter. Ten of 17 transgenic lines
      generated exhibited low platelet levels, each line displaying a distinct,
      heritable level of thrombocytopenia. Within a line, the degree of the platelet
      reduction correlated directly with transgene zygosity. The platelet level could
      be further reduced by the inactivation of one copy of the endogenous
      retinoblastoma gene. Western blot analysis detected large tumor antigen protein
      in the most severely affected lines; less affected lines were below the level of
      detection. Platelets and megakaryocytes from thrombocytopenic mice exhibited
      morphological abnormalities. Mice with either normal or reduced platelet levels
      developed megakaryocytic malignancies with a mean age of onset of about 8 months.
      There was no correlation between severity of thrombocytopenia and onset of
      malignancy. These mice provide a defined genetic model for thrombocytopenia, and
      for megakaryocytic neoplasia, and implicate the retinoblastoma protein in the
      process of megakaryocyte differentiation.

PMID- 7809124
TI  - Structural basis for chromosome X-linked agammaglobulinemia: a tyrosine kinase
      disease.
AB  - X-linked agammaglobulinemia (XLA) is a hereditary defect of B-cell
      differentiation in man caused by deficiency of Bruton tyrosine kinase (BTK). A
      three-dimensional model for the BTK kinase domain, based on the core structure of
      cAMP-dependent protein kinase, was used to interpret the structural basis for
      disease in eight independent point mutations in patients with XLA. As Arg-525 of
      BTK has been thought to functionally substitute for a critical lysine residue in
      protein-serine kinases, the mutation Arg-525-->Gln was studied and found to
      abrogate the tyrosine kinase activity of BTK. All of the eight mutations (Lys-430
      ->Glu, Arg-520-->Glu, Arg-525-->Gln, Arg-562-->Pro, Ala-582-->Val, Glu-589-->Gly,
      Gly-594-->Glu, and Gly-613-->Asp) were located on one face of the BTK kinase
      domain, indicating structural clustering of functionally important residues.

PMID- 7809125
TI  - Extensive oxidative DNA damage in hepatocytes of transgenic mice with chronic
      active hepatitis destined to develop hepatocellular carcinoma.
AB  - A transgenic mouse strain that expresses the hepatitis B virus (HBV) large
      envelope protein in the liver was used to determine the extent of oxidative DNA
      damage that occurs during chronic HBV infection. This mouse strain develops a
      chronic necroinflammatory liver disease that mimics the inflammation, cellular
      hyperplasia, and increased risk for cancer that is evident in human chronic
      active hepatitis. When perfused in situ with nitroblue tetrazolium, an indicator
      for superoxide formation, the liver of transgenic mice displayed intense formazan
      deposition in Kupffer cells, indicating oxygen radical production, and S-phase
      hepatocytes were commonly seen adjacent to the stained Kupffer cells. Similar
      changes were not observed in nontransgenic control livers. To determine whether
      these events were associated with oxidative DNA damage, genomic DNA from the
      livers of transgenic mice and nontransgenic controls was isolated and examined
      for 8-oxo-2'-deoxyguanosine, an oxidatively modified adduct of deoxyguanosine.
      Results showed a significant, sustained accumulation in steady-state 8-oxo-2'
      deoxyguanosine that started early in life exclusively in the transgenic mice and
      increased progressively with advancing disease. The most pronounced increase
      occurred in livers exhibiting microscopic nodular hyperplasia, adenomas, and
      hepatocellular carcinoma. Thus, HBV transgenic mice with chronic active hepatitis
      display greatly increased hepatic oxidative DNA damage. Moreover, the DNA damage
      occurs in the presence of heightened hepatocellular proliferation, increasing the
      probability of fixation of the attendant genetic and chromosomal abnormalities
      and the development of hepatocellular carcinoma.

PMID- 7809126
TI  - Replication of avocado sunblotch viroid: evidence for a symmetric pathway with
      two rolling circles and hammerhead ribozyme processing.
AB  - The structure of a series of RNAs extracted from avocado infected by the 247-nt
      avocado sunblotch viroid (ASBVd) was investigated. The identification of
      multistranded complexes containing circular ASBVd RNAs of (+) and (-) polarity
      suggests that replication of ASBVd proceeds through a symmetric pathway with two
      rolling circles where these two circular RNAs are the templates. This is in
      contrast to the replication of potato spindle tuber viroid and probably of most
      of its related viroids, which proceeds via an asymmetric pathway where circular
      (+)-strand and linear multimeric (-)-strand RNAs are the two templates. Linear
      (+) and (-) ASBVd RNAs of subgenomic length (137 nt and about 148 nt,
      respectively) and one linear (+)-strand ASBVd RNA of supragenomic length (383-384
      nt) were also found in viroid-infected tissue. The two linear (+)-strand RNAs
      have the same 5'- and 3'-terminal sequences, with the supragenomic species being
      a fusion product of the monomeric and subgenomic (+)-strand ASBVd RNAs. The 3'
      termini of these two (+)-strand molecules, which at least in the subgenomic RNA
      has an extra nontemplate cytidylate residue, could represent sites of either
      premature termination of the (+)-strands or specific initiation of the (-)
      strands. The 5' termini of sub- and supragenomic (+)-strand and the 5' terminus
      of the subgenomic (-)-strand ASBVd RNA are identical to those produced in the in
      vitro self-cleavage reactions of (+) and (-) dimeric ASBVd RNAs, respectively.
      These observations strongly suggest that the hammerhead structures which mediate
      the in vitro self-cleavage reactions are also operative in vivo.

PMID- 7809127
TI  - Dynamic interaction between Isp45 and mitochondrial hsp70 in the protein import
      system of the yeast mitochondrial inner membrane.
AB  - The protein import system of the yeast mitochondrial inner membrane includes at
      least three membrane proteins that presumably form a transmembrane channel as
      well as several chaperone proteins that mediate the import and refolding of
      precursor proteins. We show that one of the membrane proteins, Isp45, spans the
      mitochondrial inner membrane yet is extracted from this membrane at high pH.
      Solubilization of mitochondria with a nonionic detergent releases Isp45 as a
      complex with the chaperones mitochondrial hsp70 (mhsp70) and GrpEp. Both
      chaperones reversibly dissociate from Isp45 upon addition of ATP or adenosine 5'
      [gamma-thio]triphosphate, suggesting that dissociation requires the binding of
      ATP. Control experiments indicate that the interaction between mhsp70 and Isp45
      occurs in the intact mitochondria. We propose that Isp45 lines the inside of a
      proteinaceous channel across the inner membrane and that it is the membrane
      anchor for an ATP-driven "import motor" composed of mhsp70 and GrpEp. This
      arrangement is reminiscent of the protein transport systems of the yeast
      endoplasmic reticulum and the bacterial plasma membrane.

PMID- 7809128
TI  - Oncogenic capacity of the E2F1 gene.
AB  - Previous experiments have identified the E2F transcription factor as a potential
      downstream target for the action of cellular regulatory activities, such as the
      Rb tumor suppressor protein, that control cell growth and that, when altered,
      contribute to the development of human tumors. In light of these findings, we
      have assayed the ability of the E2F1 and DP1 genes, which encode heterodimeric
      partners that together create E2F activity, to act in an oncogenic fashion. We
      find that E2F1, particularly in combination with the DP1 product, cooperates with
      an activated ras oncogene to induce the formation of morphologically transformed
      foci in primary rat embryo fibroblast cultures. In addition, an E2F1 chimeric
      protein, in which sequences involved in Rb binding have been replaced with the
      herpesvirus VP16 activation domain, exhibits increased transformation activity.
      Cells transfected with E2F1 and DP1 or the E2F1-VP16 chimera form colonies in
      soft agar and induce tumor formation in nude mice. We conclude that deregulated
      E2F1 expression and function can have oncogenic consequences.

PMID- 7809129
TI  - Subunit stoichiometry of staphylococcal alpha-hemolysin in crystals and on
      membranes: a heptameric transmembrane pore.
AB  - Elucidation of the accurate subunit stoichiometry of oligomeric membrane proteins
      is fraught with complexities. The interpretations of chemical cross-linking,
      analytical ultracentrifugation, gel filtration, and low-resolution electron
      microscopy studies are often ambiguous. Staphylococcal alpha-hemolysin (alpha
      HL), a homooligomeric toxin that forms channels in cell membranes, was believed
      to possess six subunits arranged around a sixfold axis of symmetry. Here, we
      report that analysis of x-ray diffraction data and chemical modification
      experiments indicate that the alpha HL oligomer is a heptamer. Self-rotation
      functions calculated using x-ray diffraction data from single crystals of alpha
      HL oligomers show a sevenfold axis of rotational symmetry. The alpha HL pore
      formed on rabbit erythrocyte membranes was determined to be a heptamer by
      electrophoretic separation of alpha HL heteromers formed from subunits with the
      charge of wild-type alpha HL and subunits with additional negative charge
      generated by targeted chemical modification of a single-cysteine mutant. These
      data establish the heptameric oligomerization state of the alpha HL transmembrane
      pore both in three-dimensional crystals and on a biological membrane.

PMID- 7809130
TI  - Comparisons of eukaryotic genomic sequences.
AB  - A method for assessing genomic similarity based on relative abundances of short
      oligonucleotides in large DNA samples is introduced. The method requires neither
      homologous sequences nor prior sequence alignments. The analysis centers on (i)
      dinucleotide (and tri- and tetra-) relative abundance extremes in genomic
      sequences, (ii) distances between sequences based on all dinucleotide relative
      abundance values, and (iii) a multidimensional partial ordering protocol. The
      emphasis in this paper is on assessments of general relatedness of genomes as
      distinguished from phylogenetic reconstructions. Our methods demonstrate that the
      relative abundance distances almost always differ more for genomic interspecific
      sequence comparisons than for genomic intraspecific sequence comparisons,
      indicating congruence over different genome sequence samples. The genomic
      comparisons are generally concordant with accepted phylogenies among vertebrate
      and among fungal species sequences. Several unexpected relationships between the
      major groups of metazoa, fungal, and protist DNA emerge, including the following.
      (i) Schizosaccharomyces pombe and Saccharomyces cerevisiae in dinucleotide
      relative abundance distances are as similar to each other as human is to bovine.
      (ii) S. cerevisiae, although substantially far from, is significantly closer to
      the vertebrates than are the invertebrates (Drosophila melanogaster, Bombyx mori,
      and Caenorhabditis elegans). This phenomenon may suggest variable evolutionary
      rates during the metazoan radiations and slower changes in the fungal
      divergences, and/or a polyphyletic origin of metazoa. (iii) The genomic sequences
      of D. melanogaster and Trypanosoma brucei are strikingly similar. This DNA
      similarity might be explained by some molecular adaptation of the parasite to its
      dipteran (tsetse fly) host, a host-parasite gene transfer hypothesis. Robustness
      of the methods may be due to a genomic signature of dinucleotide relative
      abundance values reflecting DNA structures related to dinucleotide stacking
      energies, constraints of DNA curvature, and mechanisms attendant to replication,
      repair, and recombination.

PMID- 7809131
TI  - Heterogeneity of genomes: measures and values.
AB  - Genomic homogeneity is investigated for a broad base of DNA sequences in terms of
      dinucleotide relative abundance distances (abbreviated delta-distances) and of
      oligonucleotide compositional extremes. It is shown that delta-distances between
      different genomic sequences in the same species are low, only about 2 or 3 times
      the distance found in random DNA, and are generally smaller than the between
      species delta-distances. Extremes in short oligonucleotides include
      underrepresentation of TpA and overrepresentation of GpC in most temperate
      bacteriophage sequences; underrepresentation of CTAG in most eubacterial genomes;
      underrepresentation of GATC in most bacteriophage; CpG suppression in
      vertebrates, in all animal mitochondrial genomes, and in many thermophilic
      bacterial sequences; and overrepresentation of GpG/CpC in all animal
      mitochondrial sets and chloroplast genomes. Interpretations center on DNA
      structures (dinucleotide stacking energies, DNA curvature and superhelicity,
      nucleosome organization), context-dependent mutational events, methylation
      effects, and processes of replication and repair.

PMID- 7809132
TI  - Which bacterium is the ancestor of the animal mitochondrial genome?
AB  - We present considerable data supporting the hypothesis that a Sulfolobus- or
      Mycoplasma-like endosymbiont, rather than an alpha-proteobacterium, is the
      ancestor of animal mitochondrial genomes. This hypothesis is based on pronounced
      similarities in oligonucleotide relative abundance extremes common to animal
      mtDNA, Sulfolobus, and Mycoplasma capricolum and pronounced discrepancies of
      these relative abundance values with respect to alpha-proteobacteria. In
      addition, genomic dinucleotide relative abundance measures place Sulfolobus and
      M. capricolum among the closest to animal mitochondrial genomes, whereas the
      classical eubacteria, especially the alpha-proteobacteria, are at excessive
      distances. There are also considerable molecular and cellular phenotypic
      analogies among mtDNA, Sulfolobus, and M. capricolum.

PMID- 7809133
TI  - Construction of a bisaquo heme enzyme and binding by exogenous ligands.
AB  - The crystal structure of the His-175-->Gly (H175G) mutant of cytochrome-c
      peroxidase (EC 1.11.1.5), missing its only heme ligand, reveals that the
      histidine is replaced by solvent to give a bisaquo heme protein. This protein
      retains some residual activity, which can be stimulated or inhibited by addition
      of exogenous ligands. Structural analysis confirms the binding of imidazole to
      the heme at the position of the wild-type histidine ligand. This imidazole
      complex reacts readily with hydrogen peroxide to produce a radical species with
      novel properties. However, reactivation in this complex is incomplete
      (approximately 5%), which, in view of the very similar structures of the wild
      type and the H175G/imidazole forms, implies a critical role for tethering of the
      axial ligand in catalysis. This study demonstrates the feasibility of
      constructing heme enzymes with no covalent link to the protein and with unnatural
      ligand replacements. Such enzymes may prove useful in studies of electron
      transfer mechanisms and in the engineering of novel heme-based catalysts.

PMID- 7809134
TI  - Altered inflammatory responses in leukotriene-deficient mice.
AB  - Leukotrienes have been implicated in the regulation of immune responses,
      including inflammation and immediate hypersensitivity reactions. Here, we
      describe the phenotypic analysis of leukotriene-deficient mice generated by
      inactivation of the 5-lipoxygenase (5LO) gene. These 5LO(-/-) mice were unable to
      synthesize detectable levels of leukotrienes and were more resistant to lethal
      anaphylaxis induced by platelet-activating factor. The intensity of an acute
      inflammatory response induced by arachidonic acid was similar in 5LO(-/-) mice
      and controls. However, the response in 5LO(-/-) mice, but not in controls, could
      be virtually eliminated by a cyclooxygenase inhibitor. These data suggest that
      inflammatory responses are modulated by arachidonic acid metabolites through a
      variety of interconnected mechanisms. This has important implications for
      understanding the early events of an inflammatory response and for designing
      drugs for use in therapeutic intervention.

PMID- 7809135
TI  - An alternative Fc gamma-receptor ligand: potential role in T-cell development.
AB  - Fetal pre-T cells express low-affinity receptors for IgG (Fc gamma R) at a
      developmental stage prior to the rearrangement and expression of immunoglobulin
      genes. The present studies investigated the possible functional significance of
      Fc gamma R on fetal pre-T cells. Between 13 and 17 days of fetal development a
      subpopulation of T-cell receptor-, Thy-1+ thymocytes express for gamma R. The
      same cells contain mRNA for several forms of Fc gamma R (Fc gamma RII beta 1,
      beta 2, and Fc gamma RIII). Concurrently, a Pgp-1-, Thy-1-, surface
      immunoglobulin- fetal thymic cell binds recombinant soluble Fc gamma R. In
      principle this cell can interact with the pre-T cells through this counter
      receptor. To test this possibility anti-Fc gamma RII/III antibody (2.4G2) was
      injected into pregnant mice and then into their offspring for 6 wk postpartum.
      The injected antibody induced a slight increase in the proportion of CD4 or CD8
      single-positive, alpha/beta T cells in the thymus. However, in fetal thymic
      cultures in the presence of 2.4G2 or the recombinant soluble Fc gamma R there was
      an accelerated differentiation of thymocytes to single-positive, CD3-bright, heat
      stable antigen-dull, alpha/beta T cells. These experiments show that Fc gamma Rs
      are present on pre-T cells during early fetal thymic development, and that a non
      IgG ligand of the Fc gamma R is expressed concurrently on Thy- fetal thymocytes.
      Furthermore, the presumed interaction of Fc gamma R and the alternative ligand(s)
      influences T-cell development. IgG binding could be an adapted function of Fc
      gamma Rs, and, as shown for many members of the Ig super family, these receptors
      may have originally served as cell-cell recognition/interaction molecules
      required for hematopoietic development.

PMID- 7809136
TI  - Kinetics of T-cell receptor binding to peptide/I-Ek complexes: correlation of the
      dissociation rate with T-cell responsiveness.
AB  - Recognition by T-cell antigen receptors (TCRs) of processed peptides bound to
      major histocompatibility complex (MHC) molecules is required for the initiation
      of most T-lymphocyte responses. Despite the availability of soluble forms of TCRs
      and MHC heterodimers, this interaction has proven difficult to study directly due
      to the very low affinity. We report here on the kinetics of TCR binding to
      peptide/MHC complexes in a cell-free system using surface plasmon resonance. The
      apparent association rates for the interactions of related peptide/MHC complexes
      to one such TCR are relatively slow (900-3000 M-1.s-1) and dissociation rates are
      very fast (0.3-0.06 s-1) with t1/2 of 2-12 s at 25 degrees C. The calculated
      affinity of the engineered soluble molecules compares well with previously
      reported competition data for native TCRs or competition data reported here for
      native peptide/MHC complexes, indicating that these soluble heterodimers bind in
      the same manner as the original molecules expressed on cells. We also find that
      the peptide variants which give weaker T-cell stimulatory responses have similar
      affinities but distinctly faster dissociation rates compared with the original
      peptide (when loaded onto the MHC molecule) and that this later property may be
      responsible for their lower activity. This has implications for both downstream
      signaling events and models of TCR-peptide antagonists.

PMID- 7809138
TI  - Determination of the absolute configuration of (+)-neopentyl-1-d alcohol by
      neutron and x-ray diffraction analysis.
AB  - The absolute configuration of (+)-neopentyl-1-d alcohol, prepared by the
      reduction of 2,2-dimethylpropanal-1-d by actively fermenting yeast, has been
      determined to be S by neutron diffraction. The neutron study was carried out on
      the phthalate half ester of neopentyl-1-d alcohol, crystallized as its strychnine
      salt. The absolute configuration of the (-)-strychninium cation was first
      determined by an x-ray anomalous dispersion study of its iodide salt. The chiral
      skeleton of strychnine then served as a reference from which the absolute
      configuration of the -O-CHD-C(CH3)3 group of neopentyl phthalate was determined.
      Difference Fourier maps calculated from the neutron data showed unambiguously
      that the -O-CHD-C(CH3)3 groups of both independent molecules in the unit cell had
      the S configuration. This work proves conclusively that the yeast system reduces
      aldehydes by delivering hydrogen to the re face of the carbonyl group.
      Crystallographic details: (-)-strychninium (+)-neopentyl-1-d phthalate, space
      group P2(1) (monoclinic), a = 18.564(6) A, b = 7.713(2) A, c = 23.361(8) A, beta
      = 94.18(4) degrees, V = 3336.0(5) A3, Z = 2 (T = 100 K). Final agreement factors
      are R(F) = 0.073 for 2768 reflections collected at room temperature (x-ray
      analysis) and R(F) = 0.144 for 960 reflections collected at 100 K (neutron
      analysis).

PMID- 7809137
TI  - Expression of the neurotrophin receptor TrkC is linked to a favorable outcome in
      medulloblastoma.
AB  - Medulloblastoma, the most common malignant brain tumor of childhood, has a
      variable prognosis. Although half of the children and young adults with the
      disease survive longer than 10 years after diagnosis, the others relapse and die
      despite identical therapy. We have examined the expression of neurotrophins and
      their receptors in medulloblastoma samples snap frozen in the operating room to
      preserve RNA integrity. All tumors (n = 12) were found to express mRNA encoding
      neurotrophin 3 and its receptor TrkC. The level of trkC expression was highly
      variable, with a more than 50-fold difference between the highest and lowest
      values. By Kaplan-Meier analysis, patients with tumors expressing high levels of
      trkC mRNA had significantly longer intervals without disease progression than
      those with low levels (log-rank, P = 0.03) and a more favorable overall survival
      (log-rank, P = 0.05). Thus, trkC expression is a prognostic indicator for
      patients with medulloblastoma.

PMID- 7809139
TI  - High alpha-tomatine content in ripe fruit of Andean Lycopersicon esculentum var.
      cerasiforme: developmental and genetic aspects.
AB  - A variant of Lycopersion esculentum var. cerasiforme is described that deviates
      from the typical form of the entire species, including cultivated tomatoes, in
      possessing high levels (500-5000 micrograms/g of dry weight) of the steroidal
      alkaloid alpha-tomatine in its ripe fruits. This biotype is restricted to a tiny
      enclave in the valley of Rio Mayo, Department San Martin, Peru. Among 88
      accessions of var. cerasiforme from its present distribution in the Andes, a 90%
      association was found between high tomatine and bitter flavor; within the Mayo
      watershed, all samples from the upper drainage had bitterness and high tomatine;
      the frequency of both traits decreased to low levels toward the lower end.
      Tomatine therefore probably is the source of bitterness. Throughout L. esculentum
      tomatine is present at very high concentrations in earliest stages of fruit
      development, thereafter decreasing rapidly to midperiod, and finally diminishing
      gradually to near zero at maturity as a result of catabolism to biologically
      inert compounds, except in the variant described here. High tomatine content does
      not appear to affect adversely either the natives, among whom the bitter types
      are popular, or individuals who sampled them in this survey. Genetic
      determination of high tomatine in ripe fruits is totally recessive and appears to
      be monogenic with interaction with genes of minor effect. The prevailing pattern
      of glycoalkaloid synthesis and degradation in development of solanaceous fruits
      suggests a mechanism to protect against predation prior to ripening but to permit
      it afterward as a device to promote dispersal. In consideration of the
      nondegradative nature of the variant, its genetic determination, and very
      restricted geographic distribution, mutation to this form appears to be a random
      event of doubtful evolutionary significance.

PMID- 7809140
TI  - Transcription of histone H4, H3, and H1 cell cycle genes: promoter factor HiNF-D
      contains CDC2, cyclin A, and an RB-related protein.
AB  - Cell cycle-controlled human histone genes are coordinately expressed during S
      phase, and transcriptional regulation involves a series of trans-acting factors
      (HiNFs). The proliferation-specific factor HiNF-D interacts with multiple
      recognition motifs in histone H4, H3, and H1 promoters. Using gel shift
      immunoassays, we show that CDC2, cyclin A, and an RB-related protein are
      ubiquitous subunits of HiNF-D binding activity isolated from several cell types.
      HiNF-D levels in vivo are sensitive to okadaic acid and staurosporine, indicating
      that HiNF-D activity and/or assembly is influenced by phosphorylation status.
      Thus, HiNF-D appears to be a multicomponent phosphoprotein that participates in
      coordinate control of multiple histone H4, H3, and H1 genes during the cell
      cycle. The presence of cell cycle mediators in the HiNF-D complex suggests
      linkage between transcriptional control of histones, enzymes involved in DNA
      synthesis, and the onset of DNA replication during the G1/S phase transition.

PMID- 7809141
TI  - Transcriptional control of the tissue-specific, developmentally regulated
      osteocalcin gene requires a binding motif for the Msx family of homeodomain
      proteins.
AB  - The OC box of the rat osteocalcin promoter (nt -99 to -76) is the principal
      proximal regulatory element contributing to both tissue-specific and
      developmental control of osteocalcin gene expression. The central motif of the OC
      box includes a perfect consensus DNA binding site for certain homeodomain
      proteins. Homeodomain proteins are transcription factors that direct proper
      development by regulating specific temporal and spatial patterns of gene
      expression. We therefore addressed the role of the homeodomain binding motif in
      the activity of the OC promoter. In this study, by the combined application of
      mutagenesis and site-specific protein recognition analysis, we examined
      interactions of ROS 17/2.8 osteosarcoma cell nuclear proteins and purified Msx-1
      homeodomain protein with the OC box. We detected a series of related specific
      protein-DNA interactions, a subset of which were inhibited by antibodies directed
      against the Msx-1 homeodomain but which also recognize the Msx-2 homeodomain. Our
      results show that the sequence requirements for binding the Msx-1 or Msx-2
      homeodomain closely parallel those necessary for osteocalcin gene promoter
      activity in vivo. This functional relationship was demonstrated by transient
      expression in ROS 17/2.8 osteosarcoma cells of a series of osteocalcin promoter
      (nt -1097 to +24)-reporter gene constructs containing mutations within and
      flanking the homeodomain binding site of the OC box. Northern blot analysis of
      several bone-related cell types showed that all of the cells expressed msx-1,
      whereas msx-2 expression was restricted to cells transcribing osteocalcin. Taken
      together, our results suggest a role for Msx-1 and -2 or related homeodomain
      proteins in transcription of the osteocalcin gene.

PMID- 7809143
TI  - Direct vibrational structure of protein metal-binding sites from near-infrared
      Yb3+ vibronic side band spectroscopy.
AB  - Near-infrared Yb3+ vibronic side band (VSB) spectroscopy is used to obtain
      structural information of metal binding sites in metalloproteins. This technique
      provides a selective "IR-like" vibrational spectrum of those ligands chelated to
      the Yb3+ ion. VSB spectra of various model complexes of Yb3+ representing
      different ligand types were studied to provide references for the VSB spectra of
      Yb(3+)-reconstituted metalloproteins. Ca2+ in the calcium-binding protein
      parvalbumin and Fe3+ in the iron-transporting protein transferrin were replaced
      with Yb3+. The fluorescence of Yb3+ reconstituted into these two proteins
      exhibits weak VSBs whose energy shifts, with respect to the main 2F5/2-->2F7/2
      Yb3+ electronic transition, represent the vibrational frequencies of the Yb3+
      ligands. The chemical nature of the ligands of the Yb3+ in these proteins, as
      deduced by the observed VSB frequencies, is entirely in agreement with their
      known crystal structures. For transferrin, replacement of the 12CO3(2-) metal
      counterion with 13CO3(2-) yielded the expected isotopic shift for the VSBs
      corresponding to the carbonate vibrational modes. This technique demonstrates
      enormous potential in elucidating the localized structure of metal binding sites
      in proteins.

PMID- 7809142
TI  - A second class I ribonucleotide reductase in Enterobacteriaceae: characterization
      of the Salmonella typhimurium enzyme.
AB  - The nrdA and nrdB genes of Escherichia coli and Salmonella typhimurium encode the
      R1 and R2 proteins that together form an active class I ribonucleotide reductase.
      Both organisms contain two additional chromosomal genes, nrdE and nrdF, whose
      corresponding protein sequences show some homology to the products of the genes
      nrdA and nrdB. When present on a plasmid, nrdE and nrdF together complement
      mutations in nrdA or nrdB. We have now obtained in nearly homogeneous form the
      two proteins encoded by the S. typhimurium nrdE and nrdF genes (R1E and R2F).
      They correspond to the R1 and R2 proteins. Each protein is a homodimer. Together
      they catalyze the reduction of CDP to dCDP, using dithiothreitol or reduced
      glutaredoxin, but not thioredoxin, as an electron donor. CDP reduction is
      strongly stimulated by low concentrations of dATP, presumably acting as an
      allosteric effector. Protein R2F contains an antiferromagnetically coupled
      dinuclear iron center and a tyrosyl free radical. The E. coli and S. typhimurium
      chromosome thus have maintained the information for a potentially active
      additional class I ribonucleotide reductase, whose role in vivo is as yet
      unknown. The allosteric regulation of this enzyme differs from that of the
      normally expressed reductase.

PMID- 7809144
TI  - In vivo occupancy of the vitamin D responsive element in the osteocalcin gene
      supports vitamin D-dependent transcriptional upregulation in intact cells.
AB  - The steroid hormone vitamin D is a principal mediator of skeletal homeostasis.
      1,25-Dihydroxyvitamin D3 treatment of ROS 17/2.8 osteoblast-like cells results in
      a ligand-dependent increase in transcription of the bone-specific osteocalcin
      gene. This transcriptional upregulation requires the positive cis-acting vitamin
      D responsive element (VDRE). We have used the ligation-mediated polymerase chain
      reaction to demonstrate that protein occupancy of the VDRE within the intact cell
      correlates with increased synthesis of osteocalcin transcripts. These protein-DNA
      contacts were not present in the absence of vitamin D or in osteosarcoma cells
      (ROS 24.1) lacking the vitamin D receptor. Our results establish in intact cells
      the requirement for both ligand- and receptor-dependent occupancy of the VDRE for
      vitamin D responsive enhancement of osteocalcin gene transcription.

PMID- 7809145
TI  - Discovery of endogenous catecholamines in lymphocytes and evidence for
      catecholamine regulation of lymphocyte function via an autocrine loop.
AB  - Evidence has been obtained that catecholamines and their metabolites are present
      in single lymphocytes and extracts of T- and B-cell clones by use of capillary
      electrophoresis with electrochemical detection. Pharmacological inhibition of
      tyrosine hydroxylase reduces observed catecholamine levels, suggesting
      catecholamine synthesis by lymphocytes. Intracellular dopamine levels are shown
      to be increased by extra-cellular dopamine, suggesting a cellular-uptake
      mechanism. Furthermore, incubation with either dopamine or L
      dihydroxyphenylalanine, a precursor of dopamine, results in a dose-dependent
      inhibition of lymphocyte proliferation and differentiation. Together, these
      results suggest the presence of an autocrine loop whereby lymphocytes down
      regulate their own activity.

PMID- 7809146
TI  - Control of autoantibody affinity by selection against amino acid replacements in
      the complementarity-determining regions.
AB  - Rheumatoid factor (RF) autoantibodies can be produced in healthy individuals
      after infections or immunizations and thus escape normal tolerization mechanisms.
      It has not been clear whether such autoantibodies can undergo somatic
      hypermutation and affinity maturation similar to antibodies to exogenous
      antigens. We have investigated how these autoantibodies are regulated in normal
      individuals by analyzing the sequences of monoclonal IgM RFs obtained as
      hybridomas from donors after immunization. The variable regions undergo extensive
      hypermutation, but in contrast to antibodies against exogenous antigens, there is
      a strong selection against mutations that result in replacement of amino acids in
      the hypervariable, or complementarity-determining, regions. Furthermore, we found
      no increase in affinity of these RFs with the accumulation of mutations. This
      suggests that high-affinity variants are tolerized during the hypermutation
      process and there is a peripheral mechanism operating on certain autoreactive B
      cells that, while not deleting or anergizing all autoreactive cells, prevents the
      generation of high-affinity autoantibodies. Comparison of RFs by using the VH1 DP
      10 heavy chain variable region segment from both normal individuals and
      rheumatoid arthritis (RA) patients suggests that RF from RA patients may not be
      subject to such a controlling mechanism.

PMID- 7809147
TI  - The beetle Tribolium castaneum has a fushi tarazu homolog expressed in stripes
      during segmentation.
AB  - The genetic control of embryonic organization is far better understood for the
      fruit fly Drosophila melanogaster than for any other metazoan. A gene hierarchy
      acts during oogenesis and embryogenesis to regulate the establishment of
      segmentation along the anterior-posterior axis, and homeotic selector genes
      define developmental commitments within each parasegmental unit delineated. One
      of the most intensively studied Drosophila segmentation genes is fushi tarazu
      (ftz), a pair-rule gene expressed in stripes that is important for the
      establishment of the parasegmental boundaries. Although ftz is flanked by
      homeotic selector genes conserved throughout the metazoa, there is no evidence
      that it was part of the ancestral homeotic complex, and it has been unclear when
      the gene arose and acquired a role in segmentation. We show here that the beetle
      Tribolium castaneum has a ftz homolog located in its Homeotic complex and
      expressed in a pair-rule fashion, albeit in a register differing from that of the
      fly gene. These and other observations demonstrate that a ftz gene preexisted the
      radiation of holometabolous insects and suggest that it has a role in beetle
      embryogenesis which differs somewhat from that described in flies.

PMID- 7809148
TI  - Following the assembly of RNA polymerase-DNA complexes in aqueous solutions with
      the scanning force microscope.
AB  - The capability of the scanning force microscope (SFM) to image molecules in
      aqueous buffers has opened the exciting possibility of following processes of
      molecular assembly in real time and in near-physiological environments. This
      capability is demonstrated in this paper by following the assembly process of RNA
      polymerase-DNA complexes. DNA fragments deposited on mica and imaged in
      Hepes/MgCl2 are shown before and after Escherichia coli RNA polymerase holoenzyme
      is injected in the SFM liquid chamber. The protein can recognize and bind to
      these DNA fragments within several seconds after injection, suggesting that the
      protein and the DNA retain their native configuration after deposition and during
      SFM imaging. A time-lapse sequence depicting the process of assembly of RNA
      polymerase-DNA complexes is shown. These results represent the first step for
      acquiring the capabilities to monitor complex biomolecular processes as they take
      place in ionic solutions and to characterize their spatial organization.

PMID- 7809149
TI  - Interferon gamma-independent effects of interleukin 12 administered during acute
      or established infection due to Leishmania major.
AB  - Interleukin 12 (IL-12) is a powerful stimulus for the growth of activated T and
      natural killer cells, their generation of interferon gamma (IFN-gamma), and the
      differentiation of T helper type 1 (Th1) effector cells from naive precursors in
      vitro. These activities are consistent with the capacity of exogenous IL-12 to
      heal otherwise susceptible BALB/c mice infected with the intramacrophage parasite
      Leishmania major. Using this characterized model of CD4 cell subset
      differentiation, we examined the immunologic effects of IL-12 administered either
      at the time of infection, when naive T cells are primed, or after 14 days of
      infection, by which time CD4+ subset differentiation has occurred. Given with the
      inoculation of parasites, IL-12 induced IFN-gamma and IL-10 and markedly
      suppressed IL-4. Effects on IL-10 and IL-4 were comparable in mice with
      homozygous disruption of the IFN-gamma gene (IFN-gamma 0/0), and suppression of
      IL-4 was unchanged by administration of neutralizing anti-IL-10 antibody.
      Induction of IFN-gamma and IL-10 mRNA by IL-12 also occurred in infected SCID
      mice. Given after day 14 of infection, however, IL-12 not only induced IFN-gamma
      and IL-10 but also induced IL-4 in normal and IFN-gamma 0/0 mice. These data
      demonstrate direct effects of IL-12 independent of IFN-gamma, IL-10, and IL-4 and
      demonstrate that the ineffectiveness of IL-12 administered following infection
      with L. major correlates with resistance of differentiated Th2 cells to the IL-4
      suppressing activity of IL-12.

PMID- 7809151
TI  - Two components of transmitter release at a central synapse.
AB  - After the arrival of a presynaptic nerve impulse at an excitatory synapse in
      hippocampal neurons, the rate of neurotransmitter release increases rapidly and
      then returns to low levels with a biphasic decay. The two kinetically distinct
      components are differentially affected when Sr2+ is substituted for Ca2+ ions.
      Our findings are comparable to those of the classical studies for the frog
      neuromuscular junction, and thus the basic aspects of Ca(2+)-activated
      transmitter release machinery appear to be conserved in central synapses. The
      method we have used, in addition, permits us to estimate the average
      neurotransmitter release rate for a single bouton. The observation of
      differential Ca2+/Sr2+ sensitivity is consistent with a release mechanism
      mediated by two Ca2+ sensors with distinct Ca2+ affinities: the low-affinity Ca2+
      sensor facilitates the fast synchronous phase of release, whereas the high
      affinity sensor sustains the slow asynchronous phase of release.

PMID- 7809150
TI  - Enzyme replacement in a canine model of Hurler syndrome.
AB  - The Hurler syndrome (alpha-L-iduronidase deficiency disease) is a severe
      lysosomal storage disorder that is potentially amenable to enzyme-replacement
      therapy. Availability of a canine model of the disease and a sufficient supply of
      corrective enzyme have permitted a therapeutic trial lasting 3 mo. Recombinant
      human alpha-L-iduronidase, purified to apparent homogeneity from secretions of a
      stably transfected Chinese hamster ovary cell line, was administered i.v. to
      homozygous affected animals in doses of approximately 1 mg. The enzyme rapidly
      disappeared from the circulation in a biphasic manner, with t1/2 of 0.9 and 19
      min, respectively, and was taken up primarily by the liver. Biopsy of the liver
      before and after a very short trial (seven doses administered over 12 days)
      showed remarkable resolution of lysosomal storage in both hepatocytes and Kupffer
      cells. After weekly administration of enzyme to three affected animals over a
      period of 3 mo, the level of enzyme was about normal in liver and spleen, lower
      but significant in kidney and lung, and barely detectable (0-5% of normal) in
      brain, heart valves, myocardium, cartilage, and cornea. Light and electron
      microscopic examination of numerous tissues showed normalization of lysosomal
      storage in liver, spleen, and kidney glomeruli, but there was no improvement in
      brain, heart valves, or cornea. Even though the treated dogs developed complement
      activating antibodies against alpha-L-iduronidase, clinical symptoms could be
      prevented by slow infusion of enzyme and premedication.

PMID- 7809152
TI  - Sleep patterns are disturbed in cats infected with feline immunodeficiency virus.
AB  - Human immunodeficiency virus (HIV)-related sleep disturbances have been reported
      early in AIDS. Likewise, the feline immunodeficiency virus (FIV), a natural
      lentivirus pathogen of cats, produces a similar immunodeficiency syndrome with
      neurological sequelae. To identify the neurophysiological substrate of FIV
      infection in brain, pathogen-free cats were infected with the Maryland strain of
      FIV. Eight weeks after inoculation, all FIV-infected cats seroconverted and virus
      was detected in the cerebrospinal fluid and in the mononuclear cells of
      peripheral blood. Ten to 12 months after the FIV inoculation, inoculated and
      control cats were surgically implanted with electrodes to record the sleep/wake
      cycle. These sleep recordings were obtained under conditions controlling for
      environmental variables and instrumental adaptation. FIV-infected cats spent 50%
      more time awake than the sham-inoculated controls and exhibited many more
      sleep/waking stage shifts--i.e., 40% more than controls. In addition, FIV
      infected cats showed approximately 30% of rapid eye movement (REM) sleep
      reduction compared to controls. The latency to sleep and REM sleep onset was also
      significantly delayed in FIV-infected cats. In addition, a remarkable increase in
      cortically recorded spindle activity (8-13 Hz) was observed during slow-wave
      sleep in some infected subjects, similar to changes described in HIV-infected
      humans. Moreover, infected cats exhibited no overt signs of systemic morbidity,
      such as hyperpyrexia or body weight loss. These results indicate that FIV
      infected cats exhibit sleep abnormalities similar to the sleep disturbances
      previously described in AIDS patients and further support the feline preparation
      as a valuable animal model of HIV infection of the central nervous system.

PMID- 7809153
TI  - A putative fourth Na+,K(+)-ATPase alpha-subunit gene is expressed in testis.
AB  - The Na+,K(+)-ATPase alpha subunit has three known isoforms, alpha 1, alpha 2 and
      alpha 3, each encoded by a separate gene. This study was undertaken to determine
      the functional status of a fourth human alpha-like gene, ATP1AL2. Partial genomic
      sequence analysis revealed regions exhibiting sequence similarity with exons 3-6
      of the Na+,K(+)-ATPase alpha isoform genes. ATP1AL2 cDNAs spanning the coding
      sequence of a novel P-type ATPase alpha subunit were isolated from a rat testis
      library. The predicted polypeptide is 1028 amino acids long and exhibits 76-78%
      identity with the rat Na+,K(+)-ATPase alpha 1, alpha 2 and alpha 3 isoforms,
      indicating that ATP1AL2 may encode a fourth Na+,K(+)-ATPase alpha isoform. A 3.9
      kb mRNA is expressed abundantly in human and rat testis.

PMID- 7809155
TI  - Direct measurement of stiffness of single actin filaments with and without
      tropomyosin by in vitro nanomanipulation.
AB  - In order to explain the molecular mechanism of muscle contraction, it is crucial
      to know the distribution of the sarcomere compliance of active muscle. Here, we
      directly measure the stiffness of single actin filaments with and without
      tropomyosin, using a recently developed technique for nanomanipulation of single
      actin filaments with microneedles. The results show that the stiffness for 1
      micron-long actin filaments with and without tropomyosin is 65.3 +/- 6.3 and 43.7
      +/- 4.6 pN/nm, respectively. When the distribution of crossbridge forces along
      the actin filament is taken into account, the elongation of a 1-micron-long thin
      filament during development of isometric contraction is calculated to be
      approximately 0.23%. The time constant of force in response to a sudden length
      change is < 0.2 ms, indicating that the viscoelasticity is negligible in the
      millisecond time range. These results suggest that approximately 50% of the
      sarcomere compliance of active muscle is due to extensibility of the thin
      filaments.

PMID- 7809154
TI  - Specificity analysis of blood group Lewis-y (Le(y)) antibodies generatedagainst
      synthetic and natural Le(y) determinants.
AB  - Le(y)-reactive monoclonal antibodies (mAbs) were generated in mice by
      immunization with synthetic Le(y) neoglycoproteins or with Le(y)-expressing
      cells. Serological analysis indicated that mAbs raised against synthetic Le(y)
      (i) reacted strongly with synthetic Le(y) but poorly with natural Le(y), (ii)
      cross-reacted with Le(x) or H-type 2 structures, and (iii) were IgG1, IgG2a, or
      IgG2b. mAbs raised against Le(y)-expressing cells (i) reacted with both synthetic
      Le(y) and natural Le(y), (ii) were of two types: cross-reactive with Le(x) or H
      type 2 structures or specific for Le(y), and (iii) were IgM or IgG3. One of the
      mAbs raised against natural Le(y), mAb 3S193 (IgG3), showed high specificity for
      Le(y) in ELISA tests with synthetic Le(y) and Le(y) containing glycoproteins and
      glycolipids; it also reacted strongly in rosetting assays and cytotoxic tests
      with Le(y)-expressing cells. mAb 3S193 did not lyse O, A, AB, and B human
      erythrocytes in the presence of human complement. In flow cytometry, there was
      weak reactivity with granulocytes, a reactivity also observed with two previously
      described highly specific Le(y) mouse mAbs--BR55-2 (IgG3) and B3 (IgG1). A
      humanized version of mAb 3S193 has been constructed, and the specificity pattern
      and reactivity for Le(y) remain very similar to mouse mAb 3S193.

PMID- 7809156
TI  - A role for deregulated c-Myc expression in apoptosis of Epstein-Barr virus
      immortalized B cells.
AB  - When deprived of autocrine growth factors, Epstein-Barr virus (EBV)-immortalized
      B cells stop growing and die. In this study, we show that death of EBV
      immortalized cells deprived of autocrine growth factors occurred by apoptosis.
      Cycloheximide, a protein synthesis inhibitor, inhibited apoptosis, suggesting
      that de novo protein synthesis is required. Because p53, Bcl-2, and c-Myc were
      previously implicated in the induction or prevention of apoptosis in other
      systems, we assessed their possible involvement here. Unlike normal cells that
      respond to growth factor deprivation by down-regulating c-Myc expression, EBV
      immortalized cells continued to express c-Myc, p53, and Bcl-2 at levels
      comparable to those measured prior to starvation. Consistent with data
      demonstrating that c-Myc expression is sufficient to drive quiescent cells into
      the cell cycle, autocrine growth factor-deprived EBV-immortalized cells did not
      undergo growth arrest but rather continued to proliferate until death, which
      occurred randomly throughout the cell cycle. In contrast to EBV-immortalized B
      cells, normal peripheral blood B cells activated in vitro with anti-CD40
      monoclonal antibody and interleukin 4 rapidly down-regulated c-Myc expression and
      underwent growth arrest in response to growth factors and serum deprivation.
      These findings demonstrated that c-Myc expression is deregulated in EBV
      immortalized cells. Addition of antisense oligonucleotides to c-Myc specifically
      promoted the survival of starved EBV-immortalized cells and suppressed growth of
      nonstarved EBV-immortalized cells. Thus, deregulated expression of c-Myc in EBV
      immortalized cells promotes proliferation and apoptosis following autocrine
      growth factor deprivation.

PMID- 7809157
TI  - Nonrandomness in protein sequences: evidence for a physically driven stage of
      evolution?
AB  - The sequences, or primary structures, of existing biopolymers--in particular,
      proteins--are believed to be a product of evolution. Are the sequences random? If
      not, what is the character of this nonrandomness? To explore the statistics of
      protein sequences, we use the idea of mapping the sequence onto the trajectory of
      a random walk, originally proposed by Peng et al. [Peng, C.-K., Buldyrev, S. V.,
      Goldberger, A. L., Havlin, S., Sciortino, F., Simons, M. & Stanley, H. E. (1992)
      Nature (London) 356, 168-170] in their analysis of DNA sequences. Using three
      different mappings, corresponding to three basic physical interactions between
      amino acids, we found pronounced deviations from pure randomness, and these
      deviations seem directed toward minimization of the energy of the three
      dimensional structure. We consider this result as evidence for a physically
      driven stage of evolution.

PMID- 7809158
TI  - Thermodynamic procedure to synthesize heteropolymers that can renature to
      recognize a given target molecule.
AB  - We suggest a procedure to synthesize polymers with characteristics similar to
      those observed in globular proteins: renaturability and the existence of an
      "active site" capable of specifically recognizing a given target molecule. This
      procedure is investigated by computer simulation, which finds a yield of up to
      65%. We believe that, in principle, this scheme can be realized in vitro. The
      applicability of this approach as a model of prebiotic synthesis in vivo is also
      discussed.

PMID- 7809159
TI  - Interaction mating reveals binary and ternary connections between Drosophila cell
      cycle regulators.
AB  - We characterized interactions between Drosophila melanogaster cell cycle
      regulatory proteins by a yeast interaction-mating technique. The results were
      displayed as two-dimensional matrices that revealed individual binary
      interactions between proteins. Each protein (Cdi, cyclin-dependent kinase
      interactor) interacted with a distinct spectrum of cyclin-dependent kinases (Cdk)
      from Drosophila and other organisms. Some Cdis interacted with other Cdis,
      indicating that these proteins may form trimeric complexes that include Cdks.
      Similar analysis of interaction matrices may be generally useful in detecting
      other multiprotein complexes and in establishing connectivity between individual
      complex members. Moreover, such analysis may also help assign function to newly
      identified proteins, identify domains involved in protein-protein interactions,
      and aid the dissection of genetic regulatory networks.

PMID- 7809161
TI  - The inositol high-polyphosphate series blocks synaptic transmission by preventing
      vesicular fusion: a squid giant synapse study.
AB  - Presynaptic injection of inositol 1,3,4,5-tetraphosphate, inositol 1,3,4,5,6
      pentakisphosphate, or inositol 1,2,3,4,5,6-hexakisphosphate--which we denote here
      the inositol high-polyphosphate series (IHPS)--is shown to block synaptic
      transmission when injected into the preterminal of the squid giant synapse. This
      effect is not produced by injection of inositol 1,4,5-trisphosphate. The synaptic
      block is characterized by a time course in the order of 15-45 min, depending on
      the injection site in the preterminal fiber; the fastest block occurs when the
      injection is made at the terminal release site. Presynaptic voltage clamp during
      transmitter release demonstrates that IHPS block did not modify the presynaptic
      inward, calcium current. Analysis of synaptic noise at the postsynaptic axon
      shows that both the evoked and spontaneous transmitter release are blocked by the
      IHPS. Tetanic stimulation of the presynaptic fiber at frequencies of 100 Hz
      indicates that block is accompanied by gradual reduction of the postsynaptic
      response, demonstrating that the block interferes with vesicular fusion rather
      than with vesicular docking. These results, in combination with the recently
      demonstrated observation that the IHPS bind the C2B domain in synaptotagmin
      [Fukada, M., Aruga, J., Niinobe, M., Aimoto, S. & Mikoshiba, K. (1994) J. Biol.
      Chem. 269, 29206-29211], suggest that IHPS elements are involved in vesicle
      fusion and exocytosis. In addition, a scheme is proposed in which synaptotagmin
      triggers transmitter release directly by promoting the fusion of synaptic
      vesicles with the presynaptic plasmalemma, in agreement with the very rapid
      nature of transmitter release in chemical synapses.

PMID- 7809160
TI  - The methylotrophic yeast Hansenula polymorpha contains an inducible import
      pathway for peroxisomal matrix proteins with an N-terminal targeting signal (PTS2
      proteins).
AB  - Two main types of peroxisomal targeting signals have been identified that reside
      either at the extreme C terminus (PTS1) or the N terminus (PTS2) of the protein.
      In the methylotrophic yeast Hansenula polymorpha the majority of peroxisomal
      matrix proteins are of the PTS1 type. Thus far, for H. polymorpha only amine
      oxidase (AMO) has been shown to contain a PTS2 type signal. In the present study
      we expressed H. polymorpha AMO under control of the strong endogenous alcohol
      oxidase promoter. Partial import of AMO into peroxisomes was observed in cells
      grown in methanol/(NH4)2SO4-containing medium. However, complete import of AMO
      occurred if the cells were grown under conditions that induce expression of the
      endogenous AMO gene. Similar results were obtained when the heterologous PTS2
      proteins, glyoxysomal malate dehydrogenase from watermelon and thiolase from
      Saccharomyces cerevisiae, were synthesized in H. polymorpha. The import of PTS1
      proteins, however, was not affected by the growth conditions. These results
      indicate that the reduced rate of AMO import in (NH4)2SO4-grown cells is not due
      to competition with PTS1 proteins for the same import pathway. Apparently, AMO is
      imported via a separate pathway that is induced by amines and functions for PTS2
      proteins in general.

PMID- 7809162
TI  - The iron-responsive element binding protein: a target for synaptic actions of
      nitric oxide.
AB  - Molecular targets for the actions of nitric oxide (NO) have only been partially
      clarified. The dynamic properties of the iron-sulfur (Fe-S) cluster of the iron
      responsive-element binding protein (IRE-BP) suggested that it might serve as a
      target for NO produced in response to glutamatergic stimulation in neurons. In
      the present study, we demonstrate that N-methyl-D-aspartate, acting through NO,
      stimulates the RNA-binding function of the IRE-BP in brain slices while
      diminishing its aconitase activity. In addition, we demonstrate a selective
      localization of the IRE-BP in discrete neuronal structures, suggesting a
      potential role for this protein in the response of neurons to NO.

PMID- 7809163
TI  - Ablation of islet endocrine cells by targeted expression of hormone-promoter
      driven toxigenes.
AB  - Ontogenic relationships between the different types of endocrine cells in the
      islets of Langerhans were explored by generating transgenic mouse embryos in
      which cells transcribing the glucagon, insulin, or pancreatic polypeptide genes
      were destroyed through the promoter-targeted expression of the diphtheria toxin A
      chain. Embryos lacking glucagon- or insulin-containing cells did not exhibit
      alterations in the development of the nontargeted islet cell types, whereas
      embryos lacking pancreatic polypeptide gene-expressing cells also lacked
      pancreatic insulin- and somatostatin-containing cells. These results show that
      neither glucagon nor insulin gene-expressing cells are essential for the
      differentiation of the other islet endocrine-cell types. These results also
      suggest that pancreatic polypeptide gene-expressing cells are indispensable for
      the differentiation of islet beta and delta cells because the former produce a
      necessary paracrine or endocrine factor and/or operate through a cell-lineage
      relationship.

PMID- 7809164
TI  - Transporters from H-2b, H-2d, H-2s, H-2k, and H-2g7 (NOD/Lt) haplotype
      translocate similar sets of peptides.
AB  - The TAP complex transports peptides from the cytosol into the lumen of the
      endoplasmic reticulum for presentation by major histocompatibility complex class
      I molecules. A limited degree of sequence polymorphism has been observed for the
      mouse TAP1 and TAP2 genes by restriction fragment length polymorphism and
      sequence analysis. However, functional polymorphism of the TAP transporter has
      thus far been observed for the rat only. Here we examine the effect of TAP
      polymorphism on ATP dependency and peptide specificity of TAP-mediated peptide
      transport and show that, in the mouse, polymorphism in TAP genes does not
      measurably alter the function of their gene products. We conclude that TAP
      polymorphism is unlikely to contribute to the development of autoimmune diseases
      and that, in the mouse, the specificity of the TAP transporter is matched to that
      of the F pocket of the class I molecules for which it provides the peptide
      substrates.

PMID- 7809165
TI  - Signal transmission in the parallel fiber-Purkinje cell system visualized by high
      resolution imaging.
AB  - We investigated the synaptic transmission in the parallel fiber-Purkinje cell
      system at high spatio-temporal resolution by using voltage-sensitive dyes and an
      imaging system. In rat cerebellar slices, cut in the frontal plane or in a plane
      of the cerebellar surface, local electrical stimulation induced volleys of action
      potentials in the parallel fibers; subsequent postsynaptic responses from
      Purkinje cells were observed along the volleys' entire trajectories. Furthermore,
      the formation of an ordered spatial gradient in parallel fiber conduction
      velocity across the depth of the molecular layer during postnatal development was
      observed. In preparations of adult, but not of immature rats, the conduction
      velocity of parallel fibers in the deep molecular layer was faster than in its
      more superficial regions. Our observations demonstrate that parallel fibers can
      mediate Purkinje cell excitation effectively and over considerable distances in a
      well-organized spatio-temporal manner, thus supporting the classical view of the
      physiological role assigned to the parallel fibers.

PMID- 7809167
TI  - Overexpression of the gene encoding the multidrug resistance-associated protein
      results in increased ATP-dependent glutathione S-conjugate transport.
AB  - The multidrug resistance-associated protein (MRP) is a 180- to 195-kDa
      glycoprotein associated with multidrug resistance of human tumor cells. MRP is
      mainly located in the plasma membrane and it confers resistance by exporting
      natural product drugs out of the cell. Here we demonstrate that overexpression of
      the MRP gene in human cancer cells increases the ATP-dependent glutathione S
      conjugate carrier activity in plasma membrane vesicles isolated from these cells.
      The glutathione S-conjugate export carrier is known to mediate excretion of
      bivalent anionic conjugates from mammalian cells and is thought to play a role in
      the elimination of conjugated xenobiotics. Our results suggest that MRP can cause
      multidrug resistance by promoting the export of drug modification products from
      cells and they shed light on the reported link between drug resistance and
      cellular glutathione and glutathione S-transferase levels.

PMID- 7809166
TI  - Human thrombopoietin: gene structure, cDNA sequence, expression, and chromosomal
      localization.
AB  - Thrombopoietin (TPO), a lineage-specific cytokine affecting the proliferation and
      maturation of megakaryocytes from committed progenitor cells, is believed to be
      the major physiological regulator of circulating platelet levels. Recently we
      have isolated a cDNA encoding a ligand for the murine c-mpl protooncogene and
      shown it to be TPO. By employing a murine cDNA probe, we have isolated a gene
      encoding human TPO from a human genomic library. The TPO locus spans over 6 kb
      and has a structure similar to that of the erythropoietin gene (EPO). Southern
      blot analysis of human genomic DNA reveals a hybridization pattern consistent
      with a single gene locus. The locus was mapped by in situ hybridization of
      metaphase chromosome preparations to chromosome 3q26-27, a site where a number of
      chromosomal abnormalities associated with thrombocythemia in cases of acute
      myeloid leukemia have been mapped. A human TPO cDNA was isolated by PCR from
      kidney mRNA. The cDNA encodes a protein with 80% identity to previously described
      murine TPO and is capable of initiating a proliferative signal to murine
      interleukin 3-dependent BaF3 cells expressing the murine or human TPO receptor.

PMID- 7809168
TI  - Fourier-transform infrared spectroscopy and gas chromatography-mass spectrometry
      reveal a remarkable degree of structural damage in the DNA of wild fish exposed
      to toxic chemicals.
AB  - The use of gas chromatography-mass spectrometry with selected ion monitoring (GC
      MS/SIM) and Fourier-transform infrared (FT-IR) spectroscopy revealed a remarkable
      degree of damage in the hepatic DNA of fish exposed to toxic environmental
      chemicals, compared with controls. The exposed fish, which were neoplasm-free,
      were part of a population with a high incidence of liver cancer. GC-MS/SIM showed
      markedly high concentrations of hydroxyl radical-induced ring-opening products
      (e.g., 2,6-diamino-4-hydroxy-5-formamidopyrimidine) and 8-hydroxy adducts of
      adenine and guanine (e.g., 8-hydroxyguanine) in the DNA. FT-IR spectroscopy
      revealed substantial changes in spectral areas, such as those assigned to NH
      vibrations of nucleotide bases and CO vibrations of deoxyribose. This diverse and
      extensive damage to DNA provides a perspective of premalignant changes resulting
      from xenobiotic exposure and a promising basis for predicting cancer risk in
      animals and humans.

PMID- 7809171
TI  - Cloning and expression of a human P2U nucleotide receptor, a target for cystic
      fibrosis pharmacotherapy.

PMID- 7809169
TI  - Cloning and expression of a cytoskeleton-associated diacylglycerol kinase that is
      dominantly expressed in cerebellum.
AB  - A third species of diacylglycerol kinase (EC 2.7.1.107) cDNA was cloned from a
      rat brain cDNA library. The isolated cDNA encoded a 788-amino acid, 88-kDa
      polypeptide. This isozyme shared 58% identity with the previously isolated rat 80
      kDa and 90-kDa diacylglycerol kinases. EF hand motifs, cysteine-rich zinc finger
      like sequences, and putative ATP-binding site were all conserved among these
      isozymes. The 88-kDa diacylglycerol kinase was expressed specifically in brain
      and localized predominantly in cerebellar Purkinje cells. This isozyme was
      associated equally with particulate and supernatant fractions in cDNA-transfected
      COS-7 cells and dominantly with the particulate fraction in the brain. After
      Triton X-100 extraction, this isozyme remained in the detergent-insoluble
      cytoskeletal fraction of the brain and transfected COS-7 cells.

PMID- 7809170
TI  - Oxymetry deep in tissues with low-frequency electron paramagnetic resonance.
AB  - We have measured the oxygen concentration in the body water of murine FSa and
      NFSa fibrosarcomas using a new method for quantitative oxygen concentration
      determination deep in the tissues of a living animal. The measurement uses
      unusually low-frequency electron paramagnetic spectroscopy sensitive to substrate
      7 cm deep in tissue, partially deuterated spin probes (spin labels of molecular
      mass 195, approximating that of glucose) whose distribution compartment can be
      targeted with facile adduct substitution, and novel analytic techniques. We show
      that the water-compartment oxygen concentration of the tumors decreases as the
      tumor size increases and also shows a trend to decrease as radiobiologic hypoxia
      increases. An oxymetric spectral image of the tumor is presented. The technique
      will improve with larger human tissue samples. It provides the potential to
      quantitatively assess tissue hypoxia in ischemic or preischemic states in stroke
      and myocardial infarction. It will allow direct assessment of tumor hypoxia to
      determine the usefulness of radiation and chemotherapy adjuvants directed to
      hypoxic cell compartments.

PMID- 7809172
TI  - Pharmaceutical development of tablets of a new antineoplastic drug: mitonafide.
AB  - The pharmaceutical development of tablets of a 1,8 naphtalimide with
      antineoplastic activity is carried out in two steps. The preformulation step
      includes the study of those characteristics of the drug with special importance
      for the successful development of the formulation step. In this way, the low
      moisture, the low porosity and the good flowability of the drug as raw material
      allow direct compression to be taken into account, together with wet granulation
      as methods of tablet manufacture. As a result of the formulation studies, one
      formulation of tablets obtained by direct compression and another one obtained by
      wet granulation are selected. Both of them meet all the requirements imposed to a
      solid pharmaceutical form for oral administration.

PMID- 7809173
TI  - Pharmacodynamics of opioids: recent developments.
AB  - The pharmacodynamic phase of a drug describes its interaction with its biological
      receptor and the creation or prevention of a signal that subsequently leads to
      the phenomenon, the biological response. Molecular definition of the ligands
      interaction with its target proteins might be the appropriate approach for
      understanding the action of opioid and opioid-like drugs. Characterization of the
      ligand as well as of the receptor protein is essential for this rational
      approach. This review shows some aspects how far research has come. We are now at
      the beginning of understanding what perfect peptidomimetics like morphine are
      actually mimicking, an understanding, that has led to new efficient molecular
      tools for the pharmacology of opioids.

PMID- 7809174
TI  - Changes in etilefrine-induced CNS effects when associated with theophylline.
AB  - A diverse set of techniques (curiosity, chimney test, changes in barbiturate
      induced sleep time, spontaneous motor activity, swimming ability, body
      temperature) was used to study theophylline (T)-induced changes in CNS etilefrine
      (E). T antagonized the depressive effects produced by high doses of E.
      Nevertheless, the LD50 of E was not modified when both drugs were administered
      simultaneously.

PMID- 7809175
TI  - Dimerisation of levonorgestrel in solid state ultraviolet light irradiation.
AB  - UV-irradiation of levonorgestrel (1) in the crystalline state under a nitrogen
      atmosphere yielded its dimer, [17 alpha[1R-(1 alpha,2 beta,4a beta,4b alpha,10a
      alpha)]]-13-ethyl-17- [4- (2-ethyl-1,2,3,4a,4b,5,6,7,9,10,10a-dodecahydro-7-oxo-1
      phenant renyl)-1- methylen-2-oxo-butoxy]-18,19-dinorpregna-4-en-20-in-3-one(3) ,
      as the principal photoproduct. It was characterized from its spectral and
      analytical data. The single crystal X-ray crystallographic data of 1 indicated
      the possibility of its photochemical dimerisation.

PMID- 7809176
TI  - Salicylates for ulcerative colitis--their mode of action.
AB  - Delivery of 5-aminosalicylic acid to the colon by sulphasalazine, other azo
      bonded compounds and controlled-release preparations is introduced in the context
      of metabolism by epithelial cells and therapeutic efficacy in ulcerative colitis.
      Potential modes of action are then reviewed, including actions on luminal
      bacteria, epithelial cell surface receptors, cellular events (such as nitric
      oxide release or butyrate oxidation), electrolyte transport and epithelial
      permeability. Evidence for an influence of salicylates on circulating and lamina
      propria inflammatory cells is presented, as well as actions on adhesion
      molecules, chemotactic peptides and inflammatory mediators, such as eicosanoids,
      platelet-activating factor, cytokines or reactive oxygen metabolites. The precise
      mechanism will remain uncertain as long as the aetiology of ulcerative colitis is
      unknown, but a pluripotential mode of action of salicylates is an advantage when
      influencing the network of events that constitute chronic inflammation.

PMID- 7809177
TI  - Drug interactions with fibric acids.
AB  - Fibric acid derivatives may interact with other drugs and the interactions can be
      of clinical relevance. The pharmacological properties and effects of these drugs
      which pertain to their potential for drug interactions, are: (a) a very high
      binding affinity to plasma proteins, especially albumin; (b) the changes produced
      in vitamin K kinetics; (c) endoplasmic reticulum hyperplasia; (d) induction of
      cytochrome P450; (e) changes in xenobiotic-metabolizing enzymes; (f) their
      capability to have a direct effect on carbohydrate metabolism and/or regulation;
      and (g) potential pharmacokinetic interactions with antidiabetic drugs. Other
      types of interactions may affect the safety and/or the therapeutic efficacy of
      fibrates. These interactions are not necessarily risky, but may be important in
      the long term. Other clinically relevant interactions with less commonly used
      drugs have been described. Fibrates will continue to be used because they have
      proved to be safe and effective in correcting many types of dyslipidemia by
      reducing serum levels of total cholesterol and triglycerides and by increasing
      high density lipoprotein cholesterol. Furthermore, they have been proven to
      decrease morbidity and morality from coronary heart disease. Therefore, awareness
      of their potential drug interactions is most relevant to their safe clinical
      therapeutic use.

PMID- 7809178
TI  - The role of interferon in the treatment of viral hepatitis.
AB  - Chronic viral hepatitis, frequently an asymptomatic disease, can persist for
      decades. Despite the lack of symptoms, prolonged infection can lead to the
      complications of cirrhosis, liver failure and hepatocellular carcinoma. The goal
      of therapy is to reduce the risk of developing these complications and to
      eradicate the infectious pool. Patients with ongoing viral replication appear to
      be at greatest risk for developing complications. These patients have been
      targeted for treatment. Numerous randomized studies of interferon treatment of
      chronic hepatitis B and C have been published in the last 8 years. The experience
      from these studies and more recent developments will be reviewed.

PMID- 7809179
TI  - Ciliary neurotrophic factor: a review.
AB  - Ciliary neurotrophic factor (CNTF) is a 22-kDa protein predicted to share with
      leukemia inhibitory factor (LIF) and interleukin-6 a common amphipathic helical
      domain. Consistent with this prediction, the CNTF receptor complex is composed of
      the CNTF alpha receptor, the LIF beta receptor and gp130 a signalling molecule
      for LIF and interleukin-6. The major sources of synthesis of CNTF are Schwann
      cells and astrocytes, but it remains unclear how much CNTF is released from these
      glial cells and by what mechanism. In vitro, CNTF supports the survival of all
      classes of peripheral nervous system neurons plus many CNS neurons, induces
      neurite outgrowth, promotes a cholinergic phenotype in sympathetic neurons and
      arrests division of neuronal precursor cells. Several cell lines also respond to
      CNTF. In vivo, CNTF rescues several types of neurons from axotomy-induced death.
      The functions of CNTF in the development and maintenance of the nervous system
      remain enigmatic.

PMID- 7809180
TI  - Metabolic suicide genes in gene therapy.
AB  - This article reviews uses of metabolic suicide genes in gene therapy. Suicide
      genes encode novel nonmammalian enzymes that can convert a relatively nontoxic
      prodrug into a highly toxic agent. Cells genetically transduced to express such
      genes essentially commit metabolic suicide in the presence of the appropriate
      prodrug. Three metabolic suicide genes are described: herpes simplex thymidine
      kinase, Escherichia coli cytosine deaminase and varicella zoster thymidine
      kinase. Transfer and expression of these genes into mammalian cells is described.
      Preclinical models of suicide gene therapy of cancer and human immunodeficiency
      virus are discussed, and several clinical trials employing suicide genes are
      described.

PMID- 7809181
TI  - Specialists and generalists: a platonic relationship.

PMID- 7809182
TI  - A time of change.

PMID- 7809183
TI  - Tuberculosis in New York City's homeless population: a public health nightmare.

PMID- 7809184
TI  - The past is prologue--or is it? A short history of the Hopkins Medical School.

PMID- 7809185
TI  - Feminist criticism in literature and medicine.

PMID- 7809186
TI  - Tuberculosis epidemic: forgotten rules for its control.

PMID- 7809187
TI  - Questions and reflections. Surgical expectation versus reality.

PMID- 7809188
TI  - Factors in urban violence.

PMID- 7809189
TI  - Factors in urban violence.

PMID- 7809190
TI  - "Greedy doctors" continued.

PMID- 7809191
TI  - Past and present. Ghostwriting-- a "disease of academia".

PMID- 7809192
TI  - An American medical educator at the Japanese bedside.

PMID- 7809193
TI  - Developmental shifts in the ability of infants with Down syndrome to produce
      treadmill steps.
AB  - BACKGROUND AND PURPOSE: In this study, we used a dynamic systems strategy to
      examine longitudinally the ability of infants with Down syndrome to produce
      alternating steps when supported on a motorized treadmill. SUBJECTS: Seven
      infants participated, ranging in age from 8 to 11 months at entry into the study
      and 13 to 29 months at their final session. METHODS: Data were collected in the
      infants' homes on a monthly basis. Testing continued until each subject produced
      consistent alternating step patterns during three consecutive test sessions.
      RESULTS: All infants responded by producing alternating steps, on average, 13.3
      months before they walked independently, but they initiated this response at a
      wide range of chronological ages and significantly later than reported previously
      for nondisabled infants. Similar developmental variables (control parameters)
      marked the shift into responsiveness to the treadmill context for all infants
      with Down syndrome, but these variables differed from those identified for
      nondisabled infants. CONCLUSION AND DISCUSSION: With age, alternating treadmill
      stepping became a more stable response, although the relative timing of interlimb
      coordination (phase lag) of the step cycles remained quite variable across ages.
      We discuss our results relative to the usefulness of dynamic systems theory in
      understanding delayed development and the possibilities of pursuing the treadmill
      paradigm as an intervention approach.

PMID- 7809194
TI  - Does the Q angle reflect the force on the patella in the frontal plane?
AB  - BACKGROUND AND PURPOSE: The quadriceps femoris muscle angle (Q angle) is used to
      reflect the quadriceps femoris muscle's force on the patella in the frontal
      plane. We found no studies, however, that validate this assumption. The purpose
      of this study was to determine whether the Q angle can be used to represent the
      force on the patella in the frontal plane. SUBJECTS: Seven lower extremities from
      four male cadavers were dissected and investigated. METHODS: We devised a model
      in which the line of action of quadriceps femoris muscle's resultant force was
      calculated in the frontal plane on the seven lower-extremity specimens. We then
      compared these calculations with the Q angles from the same cadaver specimens.
      The differences between the measured and calculated Q angles were tested for
      significance using a paired t test. In addition, we calculated a simple linear
      regression to test the relationship between the calculated and measured Q angles.
      RESULTS: Our data showed that the angle for the average resultant force of the
      quadriceps femoris muscle was 3.90 degrees greater (P = .0003) than the measured
      Q angles. A significant relationship (r = .919, P = .0035); however, was found
      between the measured and calculated Q angles. CONCLUSION AND DISCUSSION: The Q
      angle, as measured in clinical practice, appears to reflect the angle of the
      resultant quadriceps femoris muscle force. We believe, however, that this
      measurement is significantly less than the actual quadriceps femoris muscle force
      vector and underestimates the lateral force on the patella.

PMID- 7809195
TI  - Effects of continuous therapeutic ultrasound on growth and metastasis of
      subcutaneous murine tumors.
AB  - BACKGROUND AND PURPOSE: The use of therapeutic ultrasound (US) in the presence of
      malignant neoplasms has been contraindicated in physical therapy practice despite
      a lack of convincing scientific evidence. Some studies have shown that high
      levels of US, which increase tissue temperatures greater than 42 degrees C, can
      kill tumors. We sought to determine whether the application of continuous
      therapeutic US would alter the growth or metastasis of methylcholanthrene-induced
      solid tumors in mice. SUBJECTS: Seventy-one female C57BL/6 mice, age 6 to 8
      weeks, received subcutaneous injections of 5 x 10(5) tumor cells. METHODS: When
      tumors grew to 0.5 cm in diameter, the mice were randomly assigned to either a
      control group (n = 34) or an experimental group (n = 37). The experimental group
      received 10 treatments over a 2-week period of 3-MHz continuous US at 1.0 W/cm2
      for 5 minutes, using a 0.5-cm2 sound head directly over the tumor. The control
      group received the same handling except for the US treatment. Tumor dimensions
      were measured on days 1 (baseline), 7 (midtreatment), and 14 (preexcision and
      postexcision). Tumors were weighed after excision, and the mice were evaluated by
      necropsy and histopathology of regional lymph nodes. RESULTS: All tumors grew
      larger over time, but final tumor volume and weight were larger in the
      experimental group (789 mm3 and 0.932 g) than in the control group (395 mm3 and
      0.506 g). No significant difference existed in the number of metastatic lymph
      nodes between groups. CONCLUSION AND DISCUSSION: Continuous therapeutic US
      increased the volume and weight of subcutaneous murine tumors in mice. We urge
      caution in the use of continuous therapeutic US in the areas of tumors or
      suspected tumors.

PMID- 7809196
TI  - Human resources in physical therapy: opportunities for service in a rapidly
      changing health system.
AB  - This article illuminates major considerations having an impact on the utilization
      of human resources in physical therapy. The current and potential impacts of
      health system forces and trends and health care reform, in general, and scope of
      practice, team care, supply and demand, and managed care, in particular, are
      cited and discussed. The manner in which physical therapists perceive and respond
      to health care needs and access issues and in turn the manner in which the public
      and policymakers acknowledge physical therapy's growing role in this defining of
      health and health care are both likely to create new opportunities for service.

PMID- 7809197
TI  - Forecasting requirements for physical therapists.
AB  - In response to the existing undersupply of physical therapists and the projected
      changes of the health care reform era, it is prudent for the profession to
      consider implementing a training strategy that would bring the supply of physical
      therapists in line with requirements. Before such a training strategy could be
      developed, however, the physical therapy community would need to produce a
      requirements forecast. This article compares the uses and limitations of the two
      major methods for generating health professions requirements--the "need-based"
      and "demand-based" approaches--and recommends a pragmatic, tailored approach to
      determining physical therapist requirements that uses easily obtainable data on
      staffing patterns of managed care plans. The proposed method draws from both need
      based and demand-based models to produce complementary data on which to base
      policy formation.

PMID- 7809199
TI  - Personnel resources in physical therapy: an analysis of supply, career patterns,
      and methods to enhance availability.
AB  - Describing the ever-changing supply and demand for physical therapy personnel in
      the United States is an intricate, complex, and profoundly significant task for
      the profession. In this article, a review of data relating to the supply of
      physical therapy personnel in the work force and their typical career patterns is
      presented. The estimates of the numbers of physical therapists and physical
      therapist assistants are discussed, as are problems associated with such
      estimates. Studies of career patterns of physical therapists are compared.
      Changes in the participation rates of women in the physical therapy work force
      over the last three decades are described. Career expectations, defined as both
      length and pattern of work-force participation, of entering physical therapy
      professionals are presented. Strategies to adjust the work-force participation of
      personnel through changes in the educational process, career patterns, and
      practice patterns are discussed.

PMID- 7809198
TI  - Determination of supply and requirements in physical therapy: some considerations
      and examples.
AB  - This article is an exploration of the specific application of need-based and
      demand-based models for assessing health personnel supply requirements to the
      field of physical therapy. Definitions and examples of these models are offered.
      Problems presented in the field of physical therapy in accurately defining need
      and demand are presented. Specific examples of current data collection at a
      variety of levels (professional association, private sector, state, and federal)
      are given.

PMID- 7809200
TI  - Non-cytotoxic inhibition of macrophage eicosanoid biosynthesis and effects on
      leukocyte functions and reactive oxygen species of two novel anti-inflammatory
      plant diterpenoids.
AB  - Two diterpenoids were prepared from hexane anti-inflammatory extracts of the
      Spanish herb Sideritis javalambrensis: ent-13-epi-12 alpha-acetoxymanoyl oxide (=
      "manoyl oxide F1") and ent-8 alpha-hydroxy-labda-13(16), 14-diene (= "labdane
      F2"). They were evaluated for possible anti-inflammatory actions in vitro in the
      concentration range 10(-7)M to 10(-4)M, and were compared with aspirin, sodium
      salicylate, and indomethacin. Neither compound affected superoxide generation or
      scavenging and they did not inhibit non-enzymatic lipid peroxidation. Neither
      compound affected azurophil granular enzyme secretion from activated human and
      rat neutrophils. The diterpenoids were not toxic to the leukocytes or to washed
      human erythrocytes up to 3 x 10(-5)M but at 10(-4)M some leakage of LDH or
      haemolysis was observed. However, both F1 and F2 inhibited prostaglandin E2
      generation in cultured mouse peritoneal macrophages stimulated by zymosan,
      ionophore A23187, melittin, and PMA. Labdane F2 was more potent (approximate IC50
      = 3 microM in zymosan-activated macrophages). We conclude that these two natural
      products interact with the eicosanoid system, but do not interfere with the other
      tested leukocyte functions or with reactive oxygen species, and are essentially
      non-toxic at submaximal doses. This biochemical profile distinguishes these
      diterpenoids from the anti-inflammatory polyphenolics such as flavonoids obtained
      from the genus Sideritis, and suggests that medicinal decoctions of these plants
      are likely to owe any anti-inflammatory activity to more than one bioactive
      ingredient.

PMID- 7809201
TI  - Bellidifolin: a potent hypoglycemic agent in streptozotocin (STZ)-induced
      diabetic rats from Swertia japonica.
AB  - Hypoglycemic activity-guided fractionation led to the isolation of five known
      xanthones and two triterpenoids from the ethyl acetate soluble fraction of
      Swertia japonica and their identification was based on spectroscopic methods. One
      of the triterpenes, thysanolactone, was first isolated from this plant. Among the
      xanthones, bellidifolin showed a potent and dose-dependent hypoglycemic activity
      in STZ-induced diabetic rats both in i.p. and p.o. administration. A comparative
      hypoglycemic activity of the other three xanthones together with bellidifolin was
      also studied.

PMID- 7809202
TI  - In vitro antispasmodic activity of peracetylated penstemonoside, aucubin and
      catalpol.
AB  - In vitro, the peracetates of penstemonoside, aucubin and catalpol, iridoids
      isolated from Parentucellia latifolia, antagonize the uterine muscular
      contractions induced by acetylcholine and calcium, in a similar way to
      papaverine. The antagonism is non-competitive against acetylcholine (pD2' values:
      5.60 for the peracetates of penstemonoside, 5.74 for aucubin, 5.59 for catalpol,
      and 5.32 for papaverine) and competitive against calcium (pA2 values: 6.60 for
      the peracetates of penstemonoside, 6.34 for aucubin, 6.48 for catalpol, and 6.23
      for papaverine). The two components, phasic and tonic, of the response of the vas
      deferens to potassium are reduced by the three iridoids. The reduction is similar
      for both phases. The antispasmodic activity of the three iridoids, similar to
      papaverine, is related to an inhibiting effect of extracellular calcium,
      intracellular or both.

PMID- 7809203
TI  - The role of triterpenoids in the topical anti-inflammatory activity of Calendula
      officinalis flowers.
AB  - By means of a bioassay-oriented fractionation of the CO2 extract of Calendula
      flowers, the triterpenoids are shown as the most important anti-inflammatory
      principles of the drug. Among them, the faradiol monoester appears to be the most
      relevant principle for the activity of the drug, due to its quantitative
      prevalence. The unesterified faradiol, not present in the extract, is the most
      active of the tested compounds and equals indomethacin in activity, whereas the
      monools psi-taraxasterol, lupeol, taraxasterol, and beta-amyrin are less active
      than the free diol. The anti-inflammatory activity of different CO2 extracts is
      proportional to their content of faradiol monoester, which can be taken as a
      suitable parameter for the quality control of Calendula preparations.

PMID- 7809204
TI  - Effects of aqueous extracts of six marine microalgae on smooth muscle contraction
      in rat duodenum and vas deferens.
AB  - We report the effects of aqueous extracts of six marine microalgae on responses
      to various contractile agents in isolated rat duodenum (acetylcholine, calcium
      chloride, barium chloride) and vas deferens (noradrenaline). Our results suggest
      that only extracts of Phaeodactylum tricornutum, Skeletonema costatum, and
      Chlorella stigmatophora may have pharmacological potential. Extracts of these
      three species had spasmolytic effects on responses to the three contractile
      agents in duodenum. In vas deferens, P. tricornutum and C. stigmatophora
      inhibited the contractions induced by noradrenaline, whilst S. costatum showed a
      non-dose-dependent potentiation. With the aim of elucidating their mechanisms of
      action, we are attempting to isolate the active principles present in these
      extracts.

PMID- 7809205
TI  - Immunologically active polysaccharide from Cetraria islandica.
AB  - A new alkali-soluble polysaccharide has been isolated from Iceland moss, Cetraria
      islandica (L.) Ach., by ethanol fractionation, ion-exchange chromatography, and
      gel filtration. The mean M(r) was estimated to be 18,000. Sugar and methylation
      analysis, partial hydrolysis, and 13C-NMR spectroscopy showed the polysaccharide
      to be a branched galactomannan with a backbone composed of two structural
      elements; (1-->6)-linked alpha-D-mannopyranosyl and alpha-D-(1-->6)
      galactopyranosyl units. The polysaccharide showed pronounced immunostimulating
      activity in an in vitro phagocytosis assay and in the in in vivo carbon clearance
      assay.

PMID- 7809206
TI  - Biological activities of selected marine natural products.
AB  - Sixty-nine natural products derived from Phaeophyta (brown algae), Rhodophyta
      (red algae), Porifera (sponges), Cnidaria (soft corals), and Mollusca
      (nudibranchs) were investigated for their cytotoxic, antimalarial, and
      antimicrobial effects. Fifty-six were found to mediate a positive response in one
      or more of these test systems.

PMID- 7809207
TI  - Cytotoxic and antiparasitic activity from Annona senegalensis seeds.
AB  - Several extracts of Annona senegalensis (Annonaceae) seeds were tested for
      antiparasitic activity against Leishmania major, Leishmania donovani, Trypanosoma
      brucei brucei, and for cytotoxic activity against KB and VERO cell lines.
      Fractionation of seeds extracts was mainly guided by means of a biocidal assay
      against Artemia salina nauplii. The biological activities resulted from extract
      isolated acetogenins.

PMID- 7809208
TI  - Studies on the anti-tumour, anti-bacterial, and wound-healing properties of
      dragon's blood.
AB  - Three in-vitro assays have been adopted to examine the cytotoxicity and anti
      bacterial activity of the blood-red sap of Croton lechleri from Ecuador, and to
      examine its effect upon the proliferation of endothelial cells. The sap was found
      not to be cytotoxic. Several simple phenolic compounds and diterpenes showed a
      potent anti-bacterial activity. The sap has little effect upon the proliferation
      of endothelial cells, and no single active ingredient was identified. A mechanism
      for the wound-healing property of the sap has been proposed.

PMID- 7809210
TI  - Nematicidal activities of two phytoalexins from Taverniera abyssinica.
AB  - The traditional analgesic and antipyretic Ethiopian drug "Dingetegna" is made of
      dried root material of Taverniera abyssinica A. Rich (Leguminosae). In a
      screening for nematicidal natural products, "Dingetegna" extracts showed strong
      nematicidal activities towards C. elegans. In the following, medicarpin and 4
      hydroxymedicarpin were isolated as nematicidal constituents from the extracts. In
      a microwell plate assay for nematicidal activity, both compounds exhibited an
      LD50 of 25 micrograms/ml towards C. elegans. Beside these nematicidal effects,
      weak cytotoxic and antimicrobial activities were observed. In addition, both
      compounds inhibited oxygen consumption of axenically grown C. elegans, L 1210
      cells, and filamentous fungi. Respiration in sensitive bacteria was not affected.
      In L 1210 cells, the incorporation of precursors into macromolecules was affected
      in the presence of glucose, indicating that inhibition of respiration is not the
      only target site of the compounds.

PMID- 7809209
TI  - In vitro synergism of concentrated Allium sativum extract and amphotericin B
      against Cryptococcus neoformans.
AB  - Allium sativum (garlic) derived preparations are used alone or with amphotericin
      B in Asia to treat human systemic fungal infections and cryptococcal meningitis.
      To evaluate the scientific merit of using allicin-derived compounds as an anti
      fungal drug, we prepared a concentrated A. sativum extract that contained 34%
      allicin, 44% total thiosulfinates, and 20% vinyldithiins. We found that the
      concentrated extract possessed potent in vitro fungistatic and fungicidal
      activity against 3 different isolates of Cryptococcus neoformans. The minimum
      inhibitory concentration of the concentrated garlic extract against 1 x 10(5)
      organisms of C. neoformans ranged from 6 to 12 micrograms/ml. In addition, in
      vitro synergistic fungistatic activity with amphotericin B was demonstrated
      against all isolates of C. neoformans. This study lends laboratory support for
      the treatment of cryptococcal infections with concentrated garlic extracts.

PMID- 7809211
TI  - Quercetin-induced benzophenanthridine alkaloid production in suspension cell
      cultures of Sanguinaria canadensis.
AB  - Addition of micromolar concentrations of quercetin or rutin to suspension cell
      cultures of Sanguinaria canadensis L. (bloodroot) induced the biosynthesis of
      sanguinarine and chelerythrine in a dose-dependent manner. In contrast, related
      compounds: baicalein, naringin, naringenin, catechin, caffeic acid and benzoic
      acid displayed very weak inductive activity. Of the two active flavonoids,
      quercetin was the most effective for inducing benzophenanthridine alkaloid
      biosynthesis, with doses of 100 microM increasing alkaloid production over 375%
      as compared to negative controls. Quercetin's inductive effects were similar to
      that of an elicitor derived from fungus Penicillium expansum (PE-elicitor).
      Suppression of quercetin and PE-induced alkaloid biosynthesis by low doses of
      actinomycin D (5 micrograms/ml, alpha-amanitin (20 micrograms/ml), or
      cycloheximide (1 microgram/ml) demonstrate a requirement for both RNA and de novo
      cytoplasmic protein synthesis and suggest that alterations in gene expression are
      involved in the inductive mechanism. Furthermore, quercetin-induced alkaloid
      biosynthesis was significantly reduced by pretreatment of the cells with the
      calcium chelator, EGTA (3 mM), or the calcium channel inhibitor, verapamil (100
      microM), suggesting that this process was calcium dependent.

PMID- 7809212
TI  - Sites of accumulation of the antitumor alkaloid camptothecin in Camptotheca
      acuminata.
AB  - Camptothecin is an anticancer and anti-viral alkaloid produced by the Chinese
      tree Camptotheca acuminata (Nyssaceae). Despite previous reports of low levels of
      anticancer activity in leaves of Camptotheca acuminata, we have discovered that
      camptothecin accumulates to approximately 0.4% of the dry weight of young leaves.
      This level is 1.5-fold higher than that of the seeds and 2.5-fold higher than
      that of the bark, the two currently used sources of the drug. As the leaves
      mature, the concentration and absolute amount of camptothecin decreases rapidly.
      The high levels of camptothecin in young leaves could provide an easily
      harvested, non-destructive source of this important drug.

PMID- 7809213
TI  - Pharmacological and phytochemical studies of Cephaelis axillaris.
AB  - The most significant effect, observed in the preliminary pharmacological
      evaluation of the whole ethanol extract and the alkaloidal fraction of Cephaelis
      axillaris, was the hyperemia of ears and external mucosas which was most probably
      due to an alpha-adrenergic blocking activity. In addition, both samples also
      induced a marked hypotension in normotensive as well as hypertensive (SHR) rats
      and inhibited the increases of blood pressure induced by i.v. administration of
      noradrenaline in pithed rats. The structures of the major alkaloidal components
      of the extract were elucidated on the basis of chemical characterization assays
      and IR, UV, 1H and 13C one and two-dimensional NMR analyses.

PMID- 7809214
TI  - Improved access to highly unsaturated skin irritants of the daphnane type from
      latex of Excoecaria oppositifolia.
AB  - A new and more efficient procedure was developed to obtain 5 beta
      hydroxyresiniferonol-6 alpha,7 alpha-epoxide- 9,13,14-ortho(2,4,6-decatrienoate)
      [Excoecaria factor O1] by alkaline transesterification of corresponding 20
      ester(s) genuinely present in latex of Excoecaria oppositifolia. It was obtained
      in a 10-fold better yield than previously, probably due to speeding up the
      separation procedures of the sensitive compound. O1 is an appropriate starting
      material for the preparation of the daphnane prototype irritant and tumor
      promoting orthoester simplexin (SIM) especially of a multiple tritium-labeled
      form thereof. Moreover, a new Excoecaria factor O3, i.e. the 9,13,14
      ortho(2,4,6,8-hexadecate-traenoate) of 5 beta,12 beta-dihydroxyresiniferonol-6
      alpha,7 alpha-epoxide was isolated after alkaline transesterification of a TLC
      uniform fraction, composed of corresponding 20-ester(s).

PMID- 7809215
TI  - New benzyl alcohol glycosides from Pyrus bourgaeana.
AB  - Two new aromatic glycosides, benzyl beta-D-glucopyranosyl-(1-->2)-[beta-D
      apiofuranosyl-(1-->6)]-beta- D- glucopyranoside and p-[beta-D-apiofuranosyl-(1-
      >6)]-beta-D- glucopyranosyloxy-benzylic alcohol, have been isolated from the
      aerial parts of Pyrus bourgaeana (Rosaceae). The structures were elucidated by
      spectral analyses (including 2D-NMR spectral measurements) and chemical methods.
      Arbutin and four other aromatic glycosides have also been isolated and
      identified.

PMID- 7809216
TI  - The stimulating effect of radix aconiti extract on cytokines secretion by human
      mononuclear cells.

PMID- 7809217
TI  - Biologically active compounds from the Euphorbiaceae; 2. Two triterpenoids of
      Euphorbia cyparissias.

PMID- 7809218
TI  - Determination of the effect of 8-O-(2-methyl-2-butenoyl)-5,7-dihydroxy-3
      methoxyflavone from Gnaphalium robustum on growth of Escherichia coli K-12 by
      optical density and electrical conductance measurements.

PMID- 7809219
TI  - Cranial bone grafting in children.
AB  - Computed tomographic scans of 96 patients from newborn to 21 years of age were
      reviewed to assess the thickness of the skull and diploic space. Cranial
      thickness of the parietal bone used for calvarial bone harvest was assessed.
      Analysis of the data revealed that (1) cranial bone thickness may be predicted
      reliably as a function of age, (2) the growth velocity of increasing thickness of
      the parietal bone decreased with increasing age, and (3) presence of a diploic
      space may be predicted reliably as a function of age. On the basis of this
      analysis, we recommend performing split cranial bone grafting after the age of 3
      years. In situ cranial bone grafting should not be planned prior to the age of 9
      years.

PMID- 7809220
TI  - The use of a free medialis pedis flap for resurfacing skin defects of the hand
      and digits: results in five cases.
AB  - A free medialis pedis flap was used to repair skin defects of the fingers and
      hand in five patients, the flap sizes ranging from 2 x 3 cm to 5 x 10 cm. Four
      flaps survived completely, but the largest flap turned necrotic along the dorsal
      margin, which is thought to have resulted from an incorrect flap alignment. A
      free medialis pedis flap possesses several advantages: (1) It is very thin in
      comparison with other standard free flaps; (2) it can be used for small repairs,
      unlike many conventional free flaps; (3) it possesses two draining venous
      pathways, the vena comitans and the subcutaneous veins; (4) the diameters of its
      vessels are similar to those of the fingers; (5) it provides a good color and
      texture match for finger repairs; and (6) a good recovery of protective sensation
      is achievable, probably due to its thinness. However, this flap also has some
      disadvantages: A skin graft is usually required for donor-site closure, and it
      cannot be used as a sensory flap.

PMID- 7809221
TI  - Free vascularized medial plantar flap with functioning abductor hallucis transfer
      for reconstruction of thenar defects.
AB  - We devised a medial plantar flap with a functioning abductor hallucis for
      simultaneous reconstruction of thenar skin and muscle defects. The anatomy of the
      flap was studied in five cadaver dissections before surgical attempts were made
      in patients, who in this series included three men and one woman (average age 38
      years, range 26 to 50 years). All patients were followed a minimum of 3 years
      (average 3 years and 9 months). In all cases, voluntary abduction of the thumb by
      the transferred abductor hallucis was achieved and confirmed by electromyography.
      The functioning medial plantar flap provides not only stable skin to the thenar
      area with sufficient thenar bulk but also satisfactory abduction of the thumb.

PMID- 7809222
TI  - Evaluation of changes in skeletal muscle blood flow in the dog with contrast
      ultrasonography.
AB  - Intraoperative methods to assess skeletal muscle blood flow or muscle-flap
      perfusion during vascular reconstructive surgery are limited. At present,
      techniques enable only anatomic identification of the degree of patency of large
      vessels. We report here the first use of ultrasonography to assess dynamic
      changes in skeletal muscle perfusion. Baseline blood flow in the adductor muscle
      group of the hindlimbs of seven dogs was measured with an electromagnetic flow
      probe and with contrast ultrasound using the contrast agent Albunex. Blood flow
      was manipulated in each dog pharmacologically with random administration of
      intraarterial injections of Neo-Synephrine and papaverine. After each change in
      blood flow detected by electromagnetic flow probe, flow also was assessed
      qualitatively by four independent observers who graded video-recorded contrast
      enhancement in the muscle group on a 0 to 4 scale. Videodensitometry also was
      used to generate time versus intensity curves in the adductor muscle region of
      interest. Peak pixel intensity was determined during each flow condition. A total
      of 21 flow measurements were made with each assessment scheme (electromagnetic
      flow probe, video enhancement, videodensitometry) for each condition (7 control,
      7 papaverine, 7 Neo-Synephrine). Changes in blood flow assessed by video
      enhancement scores and changes in peak pixel intensity correlated with changes
      measured by electromagnetic flow probe (r = 0.84 and 0.66, respectively). We
      conclude that contrast ultrasound may be used to detect changes in skeletal
      muscle perfusion intraoperatively. Measures of muscle perfused by visual
      inspection of contrast enhancement and videodensitometric data were in agreement
      with direct measurements of changes in skeletal muscle blood flow.

PMID- 7809223
TI  - Integrated training in plastic surgery: concept, implementation, benefits, and
      liabilities.

PMID- 7809224
TI  - Aplasia cutis congenita: failed conservative treatment.
AB  - Large scalp defects in aplasia cutis congenita present a management dilemma. In
      these lesions, prolonged conservative treatment may cause as much risk as does
      operative treatment. As a result of our experience, we suggest that one should be
      prepared to undertake early surgical intervention, rather than prolonged
      conservative treatment, for larger defects. Decreasing the size of the defect
      should decrease the risk of complications, since these appear to be related. The
      management of this condition should be a compromise of both operative and
      conservative modalities.

PMID- 7809225
TI  - Lipomatosis of the scalp and macrocephaly.
AB  - In summary, a case of macrocephaly and lipomatosis of the scalp and forehead has
      been presented. The phenotypic and clinical features found in our patient are in
      accordance with previous reports. The differential diagnosis with other
      hamartoneoplastic syndromes has been evaluated and discarded, concluding that the
      present report is in accordance with Bannayan-Zonana syndrome. However, as in
      other inherited traits, finding a genetic test to diagnose this entity remains a
      challenge.

PMID- 7809226
TI  - Primary temporal melanoma without diffuse leptomeningeal involvement: a variant
      of neurocutaneous melanosis.
AB  - Plastic surgeons who treat congenital giant nevi should be aware of the
      neurocutaneous melanosis syndrome and its variants. When neurologic symptoms are
      present concurrent with MRI evidence of central nervous system involvement,
      treatment of the cutaneous lesion must be tempered by knowledge of a poor
      prognosis. In the otherwise asymptomatic patient, the plastic surgeon should
      consider screening with MRI imaging, realizing that the clinical significance of
      a positive MRI scan without neurologic symptoms is unknown.

PMID- 7809227
TI  - Flap coverage of a large defect after excision of a massive dermatofibrosarcoma
      protuberans.
AB  - We report the case of a 62-year-old man with a huge (25 X 15 cm)
      dermatofibrosarcoma protuberans of the left flank and abdomen. This is one of the
      largest dermatofibrosarcoma protuberans lesions reported in the literature. Wide
      surgical excision of the tumor with 4-cm tumor-free margins created an extensive
      wound. Wound coverage was performed by transposing an extended rectus abdominis
      myocutaneous pedicled flap to the defect. Follow-up at 2 years revealed no
      evidence of local or regional recurrence. We present a brief review of
      dermatofibrosarcoma protuberans and a discussion of the reconstruction of such
      large defects.

PMID- 7809228
TI  - Localized Mycobacterium avium-intracellulare mastitis in an immunocompetent woman
      with silicone breast implants.
AB  - While M. avium-intracellulare has received increasing recognition due to its
      association with AIDS, silicone breast implants have come under increased FDA
      scrutiny, requiring new safety and efficacy protocols. We report a case of
      localized M. avium-intracellulare mastitis associated with a breast implant in an
      immunocompetent, HIV-negative woman who was cured with implant removal and a long
      course (6 months) of clarithromycin. Serous exudates occurring in association
      with breast implants should be cultured for acid-fast organisms. Clarithromycin
      may be a therapeutic adjunct to effectively cure these infections.

PMID- 7809229
TI  - Pseudolymphoma of the breast.
AB  - A 27-year-old woman presented with a chronic mastitis treated by subcutaneous
      mastectomy and a deepithelialized TRAM flap reconstruction. The pathology
      indicated pseudolymphoma of the breast, a rare benign condition. The course of
      treatment and a brief description of the pathology are given.

PMID- 7809230
TI  - Repair of thoracoabdominal ectopia cordis with myocutaneous flaps and
      intraoperative tissue expansion.
AB  - Thoracoabdominal ectopia cordis is a congenital malposition of the heart and
      abdominal viscera, which are externally situated, carrying an extremely poor
      prognosis. We report a case of a complete thoracoabdominal ectopia cordis that
      had undergone successful coverage over the exposed heart and abdominal contents.
      A few hours after birth, the defect was repaired with an expanded
      polytetrafluoroethylene soft-tissue patch that was gradually reduced by suture
      plication. Coverage was completed 48 hours later with bilateral pectoralis major
      and rectus abdominis myocutaneous flaps. Intraoperative tissue expansion
      minimized the cardiac compression produced by surgical reconstruction of the
      defect. Our patient, who is now 36 months old, represents the seventeenth case to
      survive reconstructive attempts.

PMID- 7809231
TI  - Heterotopic transplantation of a reattached digit.
AB  - A patient who had suffered amputations at different levels of his nondominant
      left hand, and who had initially been treated with reattachment of his index and
      long fingers, presented with a minimally functional left hand. He was then
      managed by transplantation of his reattached index finger stump to the shortened
      ring finger. This significantly improved hand function and contour and alleviated
      a painful neuroma at the former ring finger amputation site. However, compared
      with the long finger, which was reattached once, the twice-reattached finger had
      less sensibility recovery, more pronounced cold intolerance, decreased basal skin
      temperature, and a slower digital rewarming time. Thus, even though it is
      technically feasible to transfer a previously reattached digit, other possible
      physiologic limitations must be considered before doing so.

PMID- 7809232
TI  - Free sensory and nonsensory plantar flap transfers in the treatment of ischial
      decubitus ulcers.
AB  - For the treatment of ischial decubitus ulcers, a sensory plantar flap is ideal,
      because the sensory stimulation of the flap appears to contribute greatly to long
      term flap viability. When a sensory flap is not possible, a nonsensory plantar
      flap offers most of the same advantages.

PMID- 7809233
TI  - The four-poster halo vest for protection of a microvascular free-tissue transfer
      reconstruction of the scalp.
AB  - Use of a four-poster halo and corset jacket provides complete protection, access,
      and mobility for patients undergoing free-flap scalp reconstruction. This
      technique was used in a patient who required a total scalp reconstruction with a
      compound latissimus/serratus muscle free flap with good success. The case and
      technique are presented for review.

PMID- 7809234
TI  - Total en bloc reconstruction of the alar cartilage using autogenous ear
      cartilage.
AB  - A new technique is described for increasing the nasal tip by using an en bloc
      autogenous ear cartilage graft in such a manner as to create, in essence, a
      replacement of the entire ipsilateral alar cartilage.

PMID- 7809235
TI  - Reconstruction of acquired ear defects with transauricular flaps.
AB  - Retroauricular flaps based superiorly, inferiorly, or posteriorly may be tunneled
      through the ear to close a variety of acquired ear defects in a single-stage
      procedure. The technique is particularly helpful for larger, nonmarginal
      deformities in which both skin and perichondrium have been excised.

PMID- 7809236
TI  - Resurfacing the distal part of the foot with a dorsal foot skin island flap
      pedicled on the plantar vasculature.
AB  - The dorsal foot skin island flap pedicled on the plantar vasculature as a
      reconstructive entity is described. Two successful cases of resurfacing of the
      distal end of the foot with a dorsal foot island flap pedicled on the proximal
      communicating vessels and the distal communicating vessels, respectively, are
      reported, and this type of reconstructive procedure is proposed as an addition to
      existing procedures for reconstructing the distal end of the foot.

PMID- 7809237
TI  - Surgical alteration of appearance among primitive societies in New Guinea.
AB  - On the remote island of New Guinea, hundreds of primitive cultures flourish as
      they have for centuries, virtually unaffected by outside influences. Among these
      tribes, practices involving intentional surgical alteration of appearance are
      common. While these practices do not exactly constitute cosmetic surgery as we
      define it, they have some interesting parallels with modern plastic surgery.
      These customs have been observed by anthropologists for decades, but relatively
      little has been written about them, and nothing has been recorded from the
      perspective of the plastic surgeon. This paper reviews descriptions made by early
      anthropologists in New Guinea, records personal observations which I made during
      two recent trips to the area, and illustrates these customs with photographs of
      contemporary tribespeople. An examination of these unusual practices provides
      insight into the underlying impulses that motivate people from radically
      different cultures to intentionally alter their appearance.

PMID- 7809238
TI  - A mobile photo stand for close-up intraoperative viewing of photographs/graphics.

PMID- 7809239
TI  - Leading causes of facial trauma in the major trauma outcome study.

PMID- 7809240
TI  - Another technique for earlobe reconstruction.

PMID- 7809241
TI  - Marjolin's ulcer of the scalp after 45 years.

PMID- 7809242
TI  - Basal cell carcinoma in a vaccination scar.

PMID- 7809243
TI  - The reuse of tissue expanders in developing countries.

PMID- 7809244
TI  - Classification of monitoring methods for vascularized transplants.

PMID- 7809245
TI  - The application of human ovaries and testes cross-sex transplantation in sex
      reassignment surgery of transsexuals (abstract)

PMID- 7809246
TI  - Sternal coverage after infection: a small handicap?

PMID- 7809247
TI  - Acceptability of sternal scars in reduction of massively enlarged breasts.

PMID- 7809248
TI  - Problem of valves in the cephalic vein used for microvascular anastomosis.

PMID- 7809249
TI  - The distal stump of the radial artery in free radial forearm flap reconstruction.

PMID- 7809250
TI  - Locally inducing high expression of tissue nonspecific alkaline phosphatase might
      regulate scar tissue maturation.

PMID- 7809251
TI  - Self-fabricated two-point discriminator tester.

PMID- 7809252
TI  - Preventing loss of surgical sponges.

PMID- 7809253
TI  - Dressing for skin grafts of the penis.

PMID- 7809254
TI  - A constriction ring of the thigh secondary to a rubber band.

PMID- 7809255
TI  - Mask lift and facial aesthetic sculpturing.
AB  - Paul Tessier started the great adventure of sculpturing the malformed face more
      than 30 years ago. Key procedures such as subperiosteal dissection and lifting of
      the facial mask, bone grafting from a cranial site of harvest, and lateral
      canthopexies have been utilized and have withstood the trial of time in thousands
      of patients. The mask lift with facial aesthetic sculpturing, a newcomer in
      aesthetic surgery, is an extrapolation of these craniofacial procedures. It is a
      different and revolutionary approach to the aging face that seeks to normalize,
      rejuvenate, and embellish the face through a subperiosteal lift of the facial
      mask and transformation of the underlying structures. Facial aesthetic
      sculpturing refers to the aesthetic sculpturing of the facial skeleton. It allows
      us to equilibrate the components of a malformed face and normalize it by
      osteotomies, displacements in three dimensions, and bone overgrafting; to
      normalize the forms of an unattractive face and to embellish it by harmonization
      of the skeletal volume; and to restore the forms of an aging face and to
      rejuvenate it by augmenting resorbed bone, reducing hypertrophic bone, and
      lifting the facial mask. My experience includes 350 patients operated on from
      1981 to 1992, of these, 200 cases were purely aesthetic, 150 functional. The
      complications encountered have been few. The technique described offers an
      appropriate response to the different problems of aging and embellishment of a
      face, whether for reequilibration of osseous volumes or for sagging of soft
      tissues of the superior two-thirds of the face. Facial aesthetic sculpturing
      finds application also in some malformations and acquired deformities and in
      young faces with unsightly features.

PMID- 7809256
TI  - Iatrogenic penile gangrene: 10-year follow-up.

PMID- 7809257
TI  - Doctor-patient relationship.

PMID- 7809258
TI  - Progressive late seroma as an uncommon cause of wound dehiscence and expander
      extrusion.

PMID- 7809259
TI  - Garlic as a possible risk for postoperative bleeding.

PMID- 7809260
TI  - Why there should not be health system reform without legal reform.

PMID- 7809261
TI  - Aplasia cutis congenita of the scalp in five successive generations of one
      family.

PMID- 7809262
TI  - Pedicle deepithelialization in breast reduction and mastopexy using the electric
      dermatome.

PMID- 7809263
TI  - Two-dimensional color Doppler imaging for tram flap perforators.

PMID- 7809264
TI  - John T. Hueston, M.D. (1926-1994).

PMID- 7809265
TI  - The suborbicularis oculi fat pads: an anatomic and clinical study.
AB  - After the concept of retro-orbicularis oculi fat had been developed, the authors
      focused in particular on the anatomic entity named suborbicularis oculi fat,
      consisting of the supraperiosteal submuscular fat excess situated over the
      zygoma. Its correction is demonstrated as well as its anatomic description and
      the fact that it contributes to the aesthetic deformity of the lower lids, just
      as the retro-orbicularis oculi fat contributes to the aesthetic deformity of the
      upper lids. The purpose of this paper is to study the upper and lower orbital
      areas, where a new approach is advocated for their correction in solo or in
      combination with a blepharoplasty.

PMID- 7809266
TI  - The tension nose: open structure rhinoplasty approach.
AB  - The term tension nose is known to many rhinoplastic surgeons, yet confusion
      exists as to its precise meaning. We define the tension deformity as excessive
      growth of the quadrilateral cartilage, resulting in a high nasal dorsum and
      anterior and sometimes inferior displacement of the nasal tip cartilages. A
      review of the surgical literature shows that little attention has been given to
      the evaluation and management of this problem. We reviewed 50 consecutive primary
      rhinoplasty candidates and found that 46 percent had some manifestation of
      tension deformity that required correction at the time of surgery. The techniques
      of open structure rhinoplasty are ideally suited to manage the tension nose. The
      essence of correction is a deprojection-reprojection process. First, excessive
      elements of the septal cartilage and anterior nasal spine, which comprise what we
      have termed the nasal pedestal, are reduced, resulting in tip deprojection. Open
      structure methods are then employed to achieve reprojection of the domes by using
      cartilage grafts and suturing techniques to build strength, support, and elegance
      into the nasal tip.

PMID- 7809267
TI  - Complications associated with the harvesting of cranial bone grafts.
AB  - This study was undertaken to determine the incidence of serious neurologic injury
      associated with the harvesting of cranial bone grafts. A personal series of 1000
      consecutive bone-grant harvestings (cranial, iliac, costal, tibial, and
      mandibular) was examined in detail for complications. Then a survey of members of
      the International Society of Craniofacial Surgeons was performed, and data were
      compiled on complications of bone-graft harvestings performed by the respondents.
      Data also were compiled on neurologic complications related to cranial bone-graft
      harvestings performed by other surgeons which the respondents were aware of
      through direct personal knowledge, medicolegal review, the medical literature, or
      other channels. No neurologic complications were associated with any of the 586
      cranial bone grafts taken in the authors' series. The survey respondents reported
      that they had performed 12,672 cranial bone-graft harvestings. Temporary
      neurologic complications were associated with graft harvesting in 3 cases (0.02
      percent). The respondents also identified 8 other neurologic complications (4
      permanent and 4 temporary) associated with cranial bone-graft harvestings
      performed by other surgeons. Five cases were performed by surgeons having little
      or no experience in harvesting cranial bone grafts, and three were performed by
      surgeons having only limited training. It appears that cranial bone grafts can be
      harvested with an extremely low incidence of serious complications by surgeons
      who have had proper training. Techniques are suggested for safe harvesting of
      cranial bone grafts, as well as for detecting and managing complications when
      they arise.

PMID- 7809268
TI  - Transpalpebral approach to the corrugator supercilii and procerus muscles.
AB  - The most effective method for treating glabellar area skin contour irregularities
      produced by hyperactive corrugator supercilii and/or procerus muscles is
      resection of the former and at least transection of the latter. The usual
      surgical approach is a coronal incision, which produces recognized sequelae of
      scalp or prefrontal hairline scarring and scalp dysesthesia; potential
      complications include injury to the frontal branch of the facial nerve,
      postoperative alopecia, and excessive recession of the frontal hairline.
      Hyperactive corrugator supercilii muscles may be excised and procerus muscles
      transected without a coronal incision. These muscles can be treated through an
      upper blepharoplasty incision without compromise to the blepharoplasty procedure.
      A transpalpebral technique as performed on 40 patients followed 6 to 24 months is
      described, and the cadaver and nerve block studies upon which this technique is
      based are discussed. The postoperative cosmetic improvement of the glabellar area
      is comparable in appearance with that achieved from a coronal incision approach.

PMID- 7809269
TI  - Silicone gel implant explantation: reasons, results, and admonitions.
AB  - Managing the patient who requests removal of her silicone gel implants, either
      intact or ruptured, can be difficult because the treatment depends on the desires
      and perceptions of the individual patient, especially in the present absence of
      data concerning the possible long-term adverse consequences of a silicone gel
      implant, intact or ruptured. Over 12 months, 46 women underwent removal of 74
      silicone gel implants placed for augmentation in 26 and reconstruction in 20.
      Reason for removal was fear of possible consequences of the silicone gel in 17
      patients, aesthetic concerns related to encapsulation in 14, systemic symptoms in
      8, rupture determined by mammography in 7, and fear of interference with
      mammography or clinical examination for breast cancer in 4. Ten of 26 augmented
      patients rejected replacement because of their concern about saline devices, but
      only 2 of 20 reconstructed patients declined. Capsulectomy was performed in 34
      patients (74 percent). Mammography correctly predicted gel implant rupture in 7
      of 8 patients. Eleven of 46 consecutive explantations were broken during removal.
      Only 1 of 7 patients with severe systemic symptoms was asymptomatic
      postoperatively, but with no changes in laboratory values. Two patients had 3
      implants (6.5 percent) deflate at 10, 13, and 90 days as a result of
      manufacturing defects. Subcutaneous mastectomy patients (5) had the least
      aesthetic improvement because of prominent rippling of the anterior skin of their
      breasts. Two patients developed infection after capsulectomy. We conclude that
      patients seeking explantation of silicone gel implants because of fear of the
      possible adverse effects of the silicone will be pleased despite aesthetic
      limitations.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7809270
TI  - Evaluation of autogenous tissue breast reconstruction using MRI.
AB  - Recent controversy encountered with silicone breast implants has increased the
      use of autogenous tissue for breast reconstruction following mastectomy.
      Surveillance of patients who have undergone autogenous tissue reconstruction is
      important in the evaluation of recurrent or new cancer. Magnetic resonance
      imaging (MRI) has proven to be a useful technique in the delineation of soft
      tissues and provides excellent resolution. Recently, MRI has been reported to be
      a valuable diagnostic imaging modality for the evaluation of augmented breast
      implant patients with regard to implant rupture detection, silicone granuloma
      identification, and silicone gel migration delineation. In this study, various
      autologous tissue donor sites currently available for breast reconstruction were
      imaged by MRI. The following donor flaps were included: fleur-de-lis, TRAM,
      gluteal, and tensor fasciae latae. A total of 10 clinical cases were
      investigated. The anatomic basis of each flap type is illustrated, and various
      tissue components of flap tissue (skin, fat, and muscle) are demonstrated on MRI
      scan. Anatomic knowledge of autogenous tissue types and MRI appearance of the
      flap-breast-chest-wall interface are critical in the surveillance and follow-up
      of breast cancer patients.

PMID- 7809271
TI  - Breast reduction for symptomatic macromastia: can objective predictors for
      operative success be identified?
AB  - The purpose of this paper is to assess symptomatic macromastia, the relief of
      symptoms by operation, and predictors of symptom relief. The methods used have
      been retrospective chart review and a self-assessment patient questionnaire. One
      hundred and thirty-three patients underwent an average 1660-gm reduction. Ninety
      three percent reported a postoperative decrease in symptoms such as shoulder
      grooves and shoulder, neck, and back pain. Correlation between breast size and
      sign or symptom severity achieved significance only for the preoperative
      submammary rash (r = 0.33, p < 0.001). Patients lost an average of 8.9 lb
      postoperatively and were less overweight (49 versus 40 percent). Activity level
      increased postoperatively in 63 percent. Postoperative chest size correlated
      inversely with activity level (r = 0.35, p < 0.001). Thirty-nine percent of
      patients who took pain medications preoperatively were able to eliminate these
      postoperatively. The quantity of tissue removed did not correlate with outcome. A
      model predictive of symptom relief could not be developed (total R2 = 0.03).
      Reduction mammaplasty promoted relief of signs and symptoms of macromastia, but a
      predictive model of successful operation could not be developed.

PMID- 7809272
TI  - Laser treatment of erythematous/hypertrophic and pigmented scars in 26 patients.
AB  - Fifteen patients with erythematous/hypertrophic scars and 11 patients with
      postinflammatory hyperpigmentation were treated with a flashlamp pumped pulsed
      dye laser at 585 nm or a flashlamp pulsed-dye laser at 510 nm. An average of 1.8
      treatments resulted in an average improvement of 77 percent. Forty-seven percent
      of the patients had 100 percent improvement after one to three treatments. Eleven
      patients with postinflammatory hyperpigmentation were treated with the flashlamp
      pumped pulsed-dye laser at 510 nm with a pulse width of 300 ns. There was an
      average of 80 percent improvement with 1.45 treatments. Forty-five percent of the
      patients had 100 percent improvement after one or two treatments. The
      pathophysiology of postoperative scarring is reviewed. Theoretical reasons for
      the efficacy of laser treatment are detailed.

PMID- 7809273
TI  - The anatomy of the lower serratus anterior muscle: a fresh cadaver study.
AB  - Forty fresh cadaver dissections were studied to determine variations in the
      anatomy of the lower portion of the serratus anterior muscle. In all cases, the
      lower three to five slips of the serratus anterior muscle were supplied by one to
      three branches from the thoracodorsal artery, the so-called serratus branches.
      Three vascular patterns were identified: type I with one branch (40 percent),
      type II with two branches (50 percent), and type III with three branches (10
      percent). The mean dimensions of the lower serratus anterior flap were 18.0 x 9.0
      cm (range 12.0 x 8.0 cm to 21.0 x 15.0 cm). The mean pedicle length was 11.3 +/-
      2.8 cm (range 7.3 to 13.3 cm). A crow's foot landmark has been identified to
      facilitate flap dissection. This landmark marks the juncture of the long thoracic
      nerve and the dominant serratus branch. This juncture can be found at the
      superior border of the sixth or seventh rib. The lower serratus anterior flap is
      ideal for reconstruction of small to moderate-sized defects because of its flat,
      broad dimensions and its long vascular pedicle.

PMID- 7809274
TI  - Expression of the ColE3 operon in maxicells.
AB  - The cea, cei, and cel genes of the ColE3 operon were localized and characterized
      by subcloning and by transposon mutagenesis. Plasmids containing different
      portions of the ColE3 operon were transformed into an E. coli maxicell strain
      CSR603. Proteins encoded by these plasmids were analyzed by SDS-PAGE after UV
      irradiation of the cells. The results showed that the molecular weights of Col,
      ImmE8, ImmE3 and Lys were 60 kDa, 15 kDa, 10 kDa, and 4-5 kDa, respectively.
      These results indicated that the maxicell system provides an easy and simple
      method for the identification of plasmid-encoded proteins.

PMID- 7809275
TI  - Protamine-induced acute lung injury and the protective effect of agents that
      increase cAMP.
AB  - Polycations, such as protamine sulfate and polylysine, have been implicated in
      acute lung injury. We studied the vascular effect of protamine sulfate and the
      protective effect of agents that increase cAMP in isolated rat lungs perfused
      with a cell- and plasma-free solution. Protamine sulfate (3 mg) markedly
      increased pulmonary artery pressure (PAP) from 15.6 +/- 0.5 to 30.8 +/- 1.2 mmHg
      (P < 0.01) and lung weight gain (LWG) by 7.8 +/- 1.5 g within 30 min (P < 0.001).
      The protective effects of pharmacological agents that increase intracellular cAMP
      were investigated. These agents included dibutyryl adenosine 3',5'-cyclic
      monophosphate (DBcAMP, a cAMP analogue), aminophylline and pentoxifylline (both
      are phosphodiesterase inhibitors). Pretreatment with these agents 5 min before
      protamine administration largely attenuated the increases in PAP and LWG. Because
      DBcAMP, aminophylline and pentoxifylline all share the effects of increasing
      intracellular cAMP and were effective on the protamine-induced lung changes, the
      intracellular level of cAMP could be a major determinant of lung injury. Since
      there is no blood in the perfusate, the mechanism of cAMP on cellular components
      in the blood such as neutrophils, can be ruled out. The endothelial cells are
      likely to be the target cells because charge interaction is believed to occur on
      the endothelial surface. This result will be very important in the elucidation of
      the protective effect of cAMP in acute lung injury.

PMID- 7809276
TI  - Recovery and properties of a fructooligosaccharides-producing beta
      fructofuranosidase from Aspergillus japonicus CCRC 38011.
AB  - The fungus (Aspergillus japonicus CCRC 38011) was found to be able to produce
      beta-fructofuranosidase with high transfructosylating activity (Ut), a key enzyme
      involved in synthesis of fructooligosaccharides from sucrose. The Ut
      productivities of this microorganism were 191.5 units/ml broth in a 6-L jar
      fermentor and 256.1 units/ml broth in a 1000-L pilot-fermentor in a modified
      medium containing 8% sucrose as a carbon source. Most of the Ut of this
      microorganism was found to be bound with mycelia. Incubation and sonication
      treatment extracted this enzyme from mycelia with maximum efficiencies of 66.3%
      and 44.3%, respectively. On the other hand, homogenization and freeze-thawing
      treatment had only a small effect on enzyme extraction. The soluble enzyme
      extracted from mycelia by incubation at pH 5.0 and 40 degrees C for 3 hours could
      be easily recovered and purified by acetone precipitation. The recovery of Ut
      from the crude enzyme solution was 99.5% by mixing the solution with an equal
      volume of acetone at 4 degrees C, followed by centrifugation. The purification
      factor of acetone precipitation was 15.8. The optimum pH and temperature of Ut
      was 5.0 and 65-70 degrees C, respectively. The enzyme was stable at a pH between
      4.0 and 5.0 and at a temperature below 60 degrees C.

PMID- 7809277
TI  - Antioxidant properties of fractions and polyphenol constituents from green,
      oolong and black teas.
AB  - Green, oolong and black teas were extracted with water, and then the water
      extracts were extracted separately with three types of solvent, chloroform, ethyl
      acetate and butanol, to obtain eight fractions. Major flavanol was extracted by
      EtOAc, while most of the alkaloid was in the chloroform fraction. Thearubigin was
      greatest in the butanol fraction, and most of the amino acid remained in the
      water fraction. All fractions were systematically analyzed by UV
      spectrophotometer and reverse phase HPLC for those important components existing
      in green tea, oolong tea, and black tea. The pure compounds of (-)-epicatechin
      (EC), (-)-epicatechin gallate (ECG), (-)-epigallocatechin (EGC), (-)
      epigallocatechin gallate (EGCG), free theaflavin, theaflavin monogallate-A,
      theaflavin monogallate-B, and theaflavin digallate were separated by LH-20
      chromatography and reverse phase HPLC. All fractions and pure compounds were
      assayed for antioxidant activity and lipoxygenase inhibition activity. Flavanol
      showed very strong antioxidant activity and lipoxygenase inhibition.

PMID- 7809278
TI  - The role of displacement in psychoanalysis.
AB  - Displacement is a defense mechanism employed by many other defenses and has a
      different role from all the other defenses. Locating conflicts in a new
      situation, displacement attempts to find new solutions. Dis-placement often is a
      re-placement unless it is part of the repetition-compulsion pattern. The paper
      explores the technical implications that demand special recognition of
      displacement beyond the usual analysis of the defenses. References are made to
      new research in the neurosciences.

PMID- 7809279
TI  - Understanding adaptive processes in a developmental context. A reappraisal of
      Hartmann's problem of adaptation.
AB  - Hartmann's theory of adaptation introduced the metapsychology of ego as an agent
      of adaptation to external reality as well as a defense against internal conflict.
      His notions of autonomous ego functions serving adaptation and of the child's
      biological preparedness for adaptation made a significant contribution to
      psychoanalytic developmental theory. However, the study of children developing in
      the midst of environmental discord and violence who enter such environments with
      or without an adequate endowment encourages a reappraisal of three issues in
      Hartmann's view of adaptation: (1) the developmental vicissitudes of adaptation,
      (2) the notion of an average expectable environment; and (3) the distinction
      between adaptation as state and as process. These issues are reviewed to outline
      factors that may preserve and foster adaptation for children in the face of
      adversity and chronic trauma. It is suggested that adaptation is better
      understood as the individual's reaching a relative state of autonomy vis-a-vis
      deviations from average expectable endowment, experience, or environment and as
      one that occurs not in spite of but in the context of adversity.

PMID- 7809280
TI  - Psychotherapy research and its implications for a theory of therapeutic change. A
      forty-year overview.
AB  - The Psychotherapy Research Project of The Menninger Foundation was started in the
      early 1950s, with the goal of learning more about what changes occur in
      psychoanalytic therapies (outcome) and how those changes come about (process).
      The principal findings were that psychoanalyses and psychoanalytic
      psychotherapies alike consistently were modified in a supportive direction, that
      more of the achieved changes were based on the operation of supportive mechanisms
      than was anticipated, and that, in many instances, the kinds of change achieved
      on the basis of these supportive mechanisms were indistinguishable from those
      that came about through the interpretive resolution of intrapsychic conflict. The
      final clinical accounting of PRP, Forty-Two Lives in Treatment, was published in
      1986 and included follow-ups for up to thirty years. A successor project, PRP-II,
      was started at the Langley Porter Institute in the mid-1980s and is ongoing. It
      is an effort to pursue the findings and conclusions of PRP by defining in more
      precise operational terms the concepts of psychic structure and structural change
      and then linking attained structural changes to the mechanisms, supportive or
      interpretive-expressive, by which they have come about. Scales of Psychological
      Capacities is a research instrument devised to reflect underlying structure and
      structural change.

PMID- 7809281
TI  - Rational and irrational. Remarks on the clinical gendering of language in
      psychoanalysis.
AB  - This paper extends Hartmann's skepticism about the heuristic value of the
      polarized terms "rational" and "irrational" lest they be used for future theory
      building. Clinically--now, as in ancient times--a close correlation exists
      between this polarity and that of common-parlance value judgments-
      "masculine/rational/positive" and "feminine/irrational/negative." Primitive
      ambivalence concerning the repudiation of femininity is explored here in both
      sexes. A suggestion is raised that it may be the female's capacity for pregnancy,
      rather than the infantile reaction to genital difference, that is the most vital
      underpinning of the age-old negative view of women.

PMID- 7809282
TI  - The "widening scope" reconsidered. Where do psychoanalysis and psychoanalytic
      psychotherapy meet?
AB  - This paper reviews the current status of the relationship between psychoanalysis
      and psychoanalytic psychotherapy and notes that, since the 1950s, the scope of
      indications for psychoanalysis has widened so that it has absorbed some of the
      clinical territory previously assigned to psychoanalytic psychotherapy.
      Simultaneously, these developments have brought changes in therapeutic technique
      and more blurring of the boundaries between these two approaches. By examining
      the manifestations of transference and their management both in psychoanalysis
      and in psychoanalytic psychotherapy, the author offers the view that these
      modalities of treatment, though linked in multiple ways, are basically different
      and that each has its preferential indications.

PMID- 7809283
TI  - Narcissistic defense and learning inhibition.
AB  - This paper presents the case of a gifted scientist, Mr. A, whose inhibitions
      prevented him from doing creative work. He could learn only when he grasped the
      material immediately; protracted study was painful and humiliating. The analysis
      revealed that his early narcissistic grandiosity, engendered by his precocity and
      parental admiration, persisted through the oedipal phase and then became
      organized in his character, defending against competitive feelings and castration
      anxiety. In the analysis, resolution of his oedipal conflicts, both positive and
      negative, went hand in hand with his relinquishing the narcissistic defenses,
      which freed him to work creatively. The case elucidates one aspect of work-study
      difficulties in children.

PMID- 7809284
TI  - Analytic abstinence and preoedipal disturbance.
AB  - Analytic abstinence entails a technical frustration that may have different
      meanings for those with primarily neurotic disorder and those with significant
      preoedipal pathology. It is posited that the greater the degree of preoedipal
      disturbance, the greater will be the tendency to experience the frustration of
      the technique itself as transference-laden: conflicts related to frustrating
      experiences in early childhood are revived owing to the abstinent form of
      psychoanalytic treatment. Ramifications regarding the analyst's work-ego,
      countertransference, general strategic considerations, and technical difficulties
      are discussed.

PMID- 7809285
TI  - Sexual abuse, or a delusional structure? From adolescent to young adult.
AB  - The treatment of an adolescent patient who recalled having been sexually abused
      in childhood by her father is described. In the course of treatment, various
      doubts were raised in the analyst's mind about the truth of this memory. As the
      analysis progressed, the analyst felt that the patient's responses to
      interpretations were signs of the presence of a delusional structure. When the
      patient felt that the analyst doubted her memory, or was not on her side, she
      angrily and vengefully broke off her treatment. She remains a very vulnerable
      young woman. The delusional structure contained the patient's sexual need to
      destroy the male's potency as a defense against her longing for the oedipal
      mother who, in reality, had left the patient for a new husband.

PMID- 7809286
TI  - Some impressions regarding conflict, defect, and deficit.
AB  - A distinction is drawn between "deficits" and "defects." A variety of clinical
      and theoretical issues is discussed with regard to each, including their
      involvement in conflict. The central thrust of the paper is "diagnostic" in the
      general sense of attempting to delineate varying elements of mental life. But
      inevitably such a delineation has technical implications, and these, too, are
      discussed. The question of how analytic change takes place is necessarily related
      to our concept of what there is to be changed.

PMID- 7809287
TI  - Remembered childhood artifacts. Windows to the past.
AB  - This paper explores how working with memories of childhood songs, pictures,
      poems, and stories can facilitate and deepen the analytic process. These
      artifacts are special metaphors for networks of repressed memories, in many
      respects like dream images. But unlike dream images and other early memories,
      they exist in the real world and can be verified. They provide the child with a
      scaffolding upon which to build a version of reality, putting conflictual
      situations into words, melodies, and images, and organize representations of
      relationships and affect that remain internally alive and can be reworked in
      unconscious fantasy. Three clinical examples illustrate how such associations
      enable the analysand to express ways in which the present, including the
      transference, is linked with the past.

PMID- 7809288
TI  - Shame and the superego. Clinical and theoretical considerations.
AB  - The conception of the superego as a set of compromise formations characterized by
      the calamity of parental disapproval and the striving of winning or regaining
      parental love and approval facilitates the awareness that shame and guilt are
      affects with similar fantasied contents. This paper explores the clinical value
      of this emphasis on similar fantasied contents of shame and guilt for analytic
      work with adults.

PMID- 7809289
TI  - The past unconscious and the present unconscious. A contribution to a technical
      frame of reference.
AB  - Difficulties inherent in the concept of the unconscious are considered, and a
      formulation is proposed as a contribution to the theory of psychoanalytic
      technique. The concepts of the past unconscious and the present unconscious are
      described, each having its own type of functional organization. The past
      unconscious can be regarded as acting like a dynamic "template," a structuring
      organization that gives form to current wishes or wishful fantasies, which are
      then further modified in the present unconscious before gaining access to
      consciousness. Finally, the implications of the frame of reference for
      interpretation, construction, and reconstruction in analysis are described.

PMID- 7809290
TI  - Neurotic negativism and negation in the psychoanalytic situation.
AB  - Negativistic phenomena in the treatment of neurotic children and adults are
      examined and distinctions are made among negativism, negation, and denial.
      Clinical vignettes exemplifying various forms of negativism are presented and
      viewed as expressions of developmental, defensive, or characterological aspects
      of the personality. Hartmann's seminal concepts of the genetic fallacy, change of
      function, and secondary autonomy are employed. The addition of a developmental
      view provides a broader context within which to view the patient's behavior and
      on the basis of which to formulate interpretive interventions.

PMID- 7809291
TI  - Heinz Hartmann. A memorial tribute and filial memoir.

PMID- 7809292
TI  - "How can we know the dancer from the dance?" The analysis of a five-year-old
      girl.
AB  - How the analyst and the patient shape the analysis is a complex matter varying
      with the stage of the analysis and the individual characteristics of each patient
      and analyst. Examining analytic hours from the beginning, middle, and end of a
      five-through-seven-year-old girl's treatment suggests an intricate pattern
      evolving from observing and learning toward elaborating a free-ranging, creative,
      multilevel interplay of internal dialogues and affects.

PMID- 7809293
TI  - "That darkness--is about to pass". The treatment of a dying patient.
AB  - This paper describes the psychoanalytic psychotherapy of a middle-aged woman ill
      with cancer. The patient entered treatment frightened, depressed, and feeling
      unable to endure the narcissistic humiliation of chemotherapy. She wished
      actively to abandon the struggle for life, in spite of the real possibility of a
      significant remission. Passive longings dominated her thoughts, but a good family
      situation mobilized a wish to continue the struggle. It was the immediate goal of
      the treatment to strengthen that wish by mobilizing healthy narcissistic cathexes
      that would facilitate feelings of self-esteem, personal pride, and pleasure in
      living. Treatment was conducted on a twice-weekly basis for almost three years.
      After two years it was determined that the illness was terminal, and the patient
      expressed the wish to be helped to "let go," precisely the reverse of the goal
      toward which we had previously been working. The paper describes the processes by
      which the patient was able to use the two stages of her treatment to accomplish
      her goals: to feel greater pride in life and then, with the help of a physician,
      to die as she had wished. Her final messages reflected her feeling that her
      suicide was a loving and estimable act.

PMID- 7809294
TI  - Reflections on multiple personality disorder as a developmentally complex
      adaptation.
AB  - Recent advances in the understanding of multiple personality disorder provide the
      groundwork for its creative reconciliation with psychoanalysis. This paper uses
      psychoanalytic, modern developmental, and psychological assessment perspectives
      to conceptualize multiple personality disorder as a developmentally protective
      response to chronic childhood trauma. Implications of this theory for clinical
      work with these patients are discussed.

PMID- 7809295
TI  - Heinz Hartmann--psychoanalysis and health values unfolding.

PMID- 7809296
TI  - A psychoanalytic appreciation of Giotto's mode of artistic representation and its
      implications for Renaissance art and science.
AB  - This paper applies developmental psychoanalytic and cognitive psychological
      principles to an evaluation of Giotto's Padua frescoes as pivotal in the
      transition from a medieval to a Renaissance mode of thought. The formulation
      stresses the importance of the emergence of triadic or operational thinking
      involving the coordination of multiple dimensions and the capacity for
      transforming them with reversibility, reciprocity, and conservation. This
      developmental achievement also results in an expanded sense of time and space.
      These concepts provide a basis for appreciating more fully the transition from
      the dyadic classical and medieval artistic representations to the triadic
      representations of Renaissance art, especially the contributions of Giotto's
      Padua frescoes to the development of the concept of infinity in nature, a concept
      central to both Renaissance art and science. The development of this concept in
      Renaissance thought raises a question about the relation of art and science. Two
      major modes of encoding or representing experiences are discussed--a sequential
      lexical and a nonsequential nonverbal mode (or word and thing representations).
      These formulations lead to the identification of a process that suggests that
      developments in art often precede those in science and thereby contribute to a
      fuller appreciation of Giotto's Padua frescoes as a landmark contribution with
      implications for the entirety of Renaissance thought.

PMID- 7809297
TI  - The vicissitudes of mourning. Virginia Woolf and To the Lighthouse.
AB  - We know from Virginia Woolf's diaries and letters that she intended the novel To
      the Lighthouse to be autobiographical. In a memoir written toward the end of her
      life, she stated that in writing the novel she had "ceased to be obsessed" by her
      mother, who had died when Woolf was a girl of thirteen. This paper explores the
      evolving relationship of a grown daughter with a mother long dead and the ways in
      which the writing of the novel both reflected and altered that internal
      relationship.

PMID- 7809298
TI  - Therapeutic work with a traumatized toddler.
AB  - This case report describes the psychotherapeutic treatment of a three- year-old
      boy. At the age of twenty-one months the child was attacked by a dog in the
      facial area. Symptoms of posttraumatic stress disorder consistent with patterns
      seen in older children and adults and significant developmental disruptions had
      persisted up to the time of the treatment. The therapeutic work illustrates the
      unique contributions that psychoanalytic approaches can make to the treatment of
      posttraumatic stress disorders in children. It appears to have contributed
      significantly to resolution of the overwhelming feelings evoked by the trauma,
      such that the child's development could resume its normal course. The case
      material highlights a number of therapeutic principles relevant to work with
      traumatized children and frames a discussion of several current issues in the
      field. A conceptual framework that delineates the effects of trauma on children
      according to seven different levels of impact is presented utilizing a
      psychoanalytically based developmental perspective.

PMID- 7809299
TI  - Differential constructions of trauma in cases of suspected child sexual
      molestation.
AB  - Despite increased attention within psychiatry and psychoanalysis to childhood
      sexual abuse, the problem of cases in which sexual abuse is suspected but cannot
      be verified has received relatively little consideration. Just as underattention
      to the possibility of molestation as a cause of sexual trauma can fail to address
      the child's environmental and therapeutic needs, so a premature conclusion that
      molestation did occur may skew the course of treatment and have adverse
      medicolegal ramifications. Although the occurrence of molestation may be
      verifiable, its absence generally cannot be proven. However, some cases of
      suspected or equivocal child sexual abuse may involve trauma other than frank
      molestation. In unclear or equivocal situations, extended diagnostic formulation
      or treatment with attention to reconstruction may lead to an explication of the
      symptoms that is at least plausible. In this report, cases thought to involve
      possible sexual molestation are presented to illustrate alternative formulations
      or constructions of the trauma. A psychoanalytic perspective can be useful in the
      approach to such cases.

PMID- 7809300
TI  - The legend of the European vampire. Object loss and corporeal preservation.
AB  - This paper reconsiders the manifold European legends of the vampire in a clinical
      context. The study of clinical psychoanalytic material that is homologous with
      these legends reveals that in both myth and clinical work, vampire legends and
      fantasies may signal experiences of object loss. Vampires are, after all, persons
      who have died but who are nonetheless immortal or "undead." This study suggests
      that an important function of vampire mythology may have been to allow the grief
      stricken to believe in the continued existence of their loved ones. Likewise, in
      the clinical analytic situation, and especially within the transference, the
      appearance of fantasy material related to vampire legends may signal bereavement,
      especially transference bereavement.

PMID- 7809301
TI  - Applying psychoanalysis in an unconventional context. Adapting infant-parent
      psychotherapy to a changing population.
AB  - The model of psychoanalytically oriented infant-parent psychotherapy originally
      proposed by Selma Fraiberg and her colleagues has evolved in the nearly two
      decades since its inception. This paper provides an overview of current
      developments in the model's core intervention techniques, with special reference
      to modifications that have emerged in response to recent efforts to intervene
      with an exceptionally psychosocially disadvantaged population. A conceptual
      framework for the intervention is offered, emphasizing the special therapeutic
      opportunities offered during the couple's transition to parenthood. Finally, the
      concept of "bureaucratic transference" will be briefly elaborated as it has
      emerged in efforts to apply psychoanalysis in work with social agencies on behalf
      of infants and their families.

PMID- 7809302
TI  - Hartmann's vision. Identical twins and developmental organizations.
AB  - This paper looks back some sixty years to Hartmann's study of identical twins.
      Examined from the vantage point of our own contemporary investigation of twins,
      Hartmann's work reveals unusual vision and contains valuable hypotheses.

PMID- 7809303
TI  - The conceptual development of regression.
AB  - Concepts of regression have evolved over time. Regression originally referred to
      a process of functional dedifferentiation and retreat to archaic forms of
      organization and function. Libidinal regression described a return to an earlier
      instinctual phase codetermined by fixations to prior points of developmental
      weakness. Within structural theory, ego and superego regression were also noted,
      without fixation points. Regression could be normal or pathological, differential
      or global, controlled or uncontrolled, and variably reversible. Historical
      emphasis on regression in pathogenesis was complemented by concepts of regression
      in the service of the ego, serving development and serving adaptation. Flexible
      regression may be contrasted with resistance to regression. Regressive and
      progressive tendencies are in continuous flux. There are new considerations of
      regression in the analytic process, and in relation to ego development and object
      relations. It is doubtful that regression per se promotes the resumption of
      arrested development.

PMID- 7809304
TI  - Reality approximated, external and internal.
AB  - Some of Heinz Hartmann's theoretical formulations concerning the adaptive
      functions of the ego are described as they apply to the case of a patient
      analyzed between the ages of five and eight. This boy, vulnerable because of
      prematurity, was born at twenty-six weeks weighing 2.7 pounds and remained in the
      hospital newborn unit for sixty-six days. Difficulties and vulnerabilities
      resulting from this experience are discussed as they appeared in the analysis.

PMID- 7809305
TI  - The exclusivity of the mother-child bond. Contributions from psychoanalytic and
      attachment theories and day-care research.
AB  - Both the psychoanalytic and the attachment theory literature have raised concerns
      about interfering with the mother-child bond during the child's first years.
      Their apprehension was that these disruptions could lead to psychopathology, some
      of which was considered serious and was classed as a disorder of attachment. The
      current research, discussed in this paper, challenges this view. Beginning in the
      first year of life, children seem capable of forming multiple bonds, while
      retaining the central importance of the mother-child bond. There is evidence that
      this core connection remains intact and has first priority in a child's mind
      regardless of other opportunities to relate. On the other hand, in spite of these
      findings, most researchers remain convinced that when the child is exposed to a
      disruption which exceeds his limits and which occurs on a chronic basis that a
      variety of disturbances may result. Some of these may be subtle and might not
      become manifest until later in the child's life. This paper attempts to explore
      the balance between the child's capacity to meet its basic needs through the core
      maternal relationship and collateral bonds, and the disruptive forces which
      actually are pathogenic.

PMID- 7809306
TI  - Marital conflict and child adjustment: an emotional security hypothesis.
AB  - An emotional security hypothesis that builds on attachment theory is proposed to
      account for recent empirical findings on the impact of marital conflict on
      children and to provide directions for future research. Children's concerns about
      emotional security play a role in their regulation of emotional arousal and
      organization and in their motivation to respond in the face of marital conflict.
      Over time these response processes and internalized representations of parental
      relations that develop have implications for children's long-term adjustment.
      Emotional security is seen as a product of past experiences with marital conflict
      and as a primary influence on future responding. The impact and interaction of
      other experiential histories within the family that affect children's emotional
      security are also examined, with a focus on parent-child relations.

PMID- 7809307
TI  - Gender differences in personality: a meta-analysis.
AB  - Four meta-analyses were conducted to examine gender differences in personality in
      the literature (1958-1992) and in normative data for well-known personality
      inventories (1940-1992). Males were found to be more assertive and had slightly
      higher self-esteem than females. Females were higher than males in extraversion,
      anxiety, trust, and, especially, tender-mindedness (e.g., nurturance). There were
      no noteworthy sex differences in social anxiety, impulsiveness, activity, ideas
      (e.g., reflectiveness), locus of control, and orderliness. Gender differences in
      personality traits were generally constant across ages, years of data collection,
      educational levels, and nations.

PMID- 7809308
TI  - Self-disclosure and liking: a meta-analytic review.
AB  - Self-disclosure plays a central role in the development and maintenance of
      relationships. One way that researchers have explored these processes is by
      studying the links between self-disclosure and liking. Using meta-analytic
      procedures, the present work sought to clarify and review this literature by
      evaluating the evidence for 3 distinct disclosure-liking effects. Significant
      disclosure-liking relations were found for each effect: (a) People who engage in
      intimate disclosures tend to be liked more than people who disclose at lower
      levels, (b) people disclose more to those whom they initially like, and (c)
      people like others as a result of having disclosed to them. In addition, the
      relation between disclosure and liking was moderated by a number of variables,
      including study paradigm, type of disclosure, and gender of the discloser. Taken
      together, these results suggest that various disclosure-liking effects can be
      integrated and viewed as operating together within a dynamic interpersonal
      system. Implications for theory development are discussed, and avenues for future
      research are suggested.

PMID- 7809309
TI  - Typologies of male batterers: three subtypes and the differences among them.
AB  - Previous typologies of male batterers, including typologies developed by means of
      rational-deductive and empirical-inductive strategies, are reviewed. On the basis
      of this review, 3 descriptive dimensions (i.e., severity of marital violence,
      generality of the violence [toward the wife or toward others], and
      psychopathology/personality disorders) that consistently have been found to
      distinguish among subtypes of batterers are identified. These dimensions are used
      to propose a typology consisting of 3 subtypes of batterers (i.e., family only,
      dysphoric/borderline, and generally violent/antisocial). A developmental model of
      marital violence is then presented, and the previous literature is reviewed to
      examine how each batterer subtype might differ on variables of theoretical
      interest. Finally, some of the methodological limitations of previous typology
      research are reviewed, and suggestions for future work are offered.

PMID- 7809310
TI  - Codetype agreement between MMPI-2 and estimated MMPI profiles in chemically
      dependent inpatients.
AB  - The extent of codetype agreement between the revised version of the Minnesota
      Multiphasic Personality Inventory (MMPI-2) and estimated MMPI profiles was
      examined in a sample of 121 inpatients being treated for chemical dependence,
      primarily alcoholism. Rates of codetype agreement among the entire sample and
      various subsamples are comparable to those reported elsewhere derived for
      different samples and using different methods. Implications for MMPI-2 codetype
      interpretation are discussed.

PMID- 7809311
TI  - On the assessment of thought disorder from the Rorschach.
AB  - While the Rorschach has been proven useful in assessing severity of thought
      disorder, the assessment of extent of thought disorder evidenced in any one
      protocol is made subjectively, that is, on the basis of clinical impression.
      Objective methods for assessing thought disorder on the Rorschach were reviewed
      and evaluated. Problems in the development of such methods which have limited
      their psychometric efficiency were discussed, and possible solutions of these
      problems were suggested. Since severity of thought disorder relates to prognosis
      and treatment, the further exploration of more effective ways of assessing
      thought disorder by the Rorschach seems warranted.

PMID- 7809312
TI  - Reliability and validity of the Ego and Discomfort Anxiety Inventory.
AB  - This article reports significant test-retest reliability scores for the Ego and
      Discomfort Anxiety Inventory. Positive significant correlations with the Fear of
      Negative Evaluation Scale supported the construct validity of the Ego Anxiety
      Scale. Positive significant correlations with the Costello-Comrey Anxiety Scale
      supported the construct validity of the Discomfort Anxiety Scale. The sample
      included 28 graduate social work students in a research methods class and 28
      undergraduate students in an introductory social work class at Michigan State
      University.

PMID- 7809313
TI  - Attitudes toward war in adolescents.
AB  - 180 college students did not differ from 31 high school students in positive
      attitudes toward war or cynicism. College students held, however, less patriotic
      attitudes.

PMID- 7809314
TI  - Gender and age differences in the drinking behaviors of university students.
AB  - A sample of 457 university students were queried concerning their use of alcohol.
      The majority (90%) of students reported drinking at least once over the past
      year, with men drinking more often. Age differences were noted, with older
      students (Mdn = 32.0 yr. vs 19.0 yr.) more likely to report drinking 4 to 6 times
      per week. Women generally had healthier attitudes concerning alcohol consumption,
      e.g., more likely to try to prevent a friend from driving after drinking, pay for
      use of a taxi, or have a designated driver. Men were more likely to indicate that
      it is socially acceptable to be intoxicated occasionally and also that most
      drinkers do not suffer health problems as a result of their drinking. The present
      study indicates a need to educate university students about the effects of
      alcohol with a particular emphasis needed for male students.

PMID- 7809315
TI  - Development of an Acculturative Stress Scale for International Students:
      preliminary findings.
AB  - Description of the development and testing of a new 36-item scale in Likert
      format, designed to assess the acculturative stress of international students,
      includes perceived discrimination, homesickness, fear, guilt, perceived hatred,
      and stress due to change (cultural shock), identified as major contributing
      factors. The psychometric properties of this instrument and implications for use
      by mental health practitioners are discussed.

PMID- 7809316
TI  - A preliminary study of opening-up meditation college adjustment, and self
      actualization.
AB  - The effects of opening-up meditation on college adjustment and self-actualization
      were examined with 45 subjects who were divided into groups for opening-up
      meditation, relaxation, and control using scores on the Anxiety Scale of the
      College Adjustment Scales. Subjects also completed the Personal Orientation
      Inventory. 1 hr. of training for the meditation and relaxation groups was given
      and 20 min./day practice requested. After 2 and 4 wk. anxiety and family problem
      scores significantly increased for the meditation group as did scores on the
      Feeling Reactivity Scale. Analysis was compromised by high dropout (leaving 3, 4,
      and 3 subjects, respectively, in the meditation, relaxation, and control groups).

PMID- 7809317
TI  - Hope, hopelessness, and suicidality in college students.
AB  - To estimate the associations among measures of hope, hopelessness, and
      suicidality, 206 undergraduates completed the Reasons for Living Inventory, the
      Hopelessness Scale, and the Hope Scale. As expected, significant correlations
      indicated that, as hope increased, hopelessness decreased. Those who scored as
      relatively more suicidal had relatively fewer feelings of total hope (Agency and
      Pathways) and more hopelessness. Further, scores on three Reasons for Living
      scales (Coping Beliefs, Family Responsibility, and Child Concerns) were
      significantly correlated in expected directions with hope and hopelessness
      scores. A stepwise multiple regression indicated that scores on Survival, Coping
      Beliefs and the Hope subscale Agency accounted for 37% of the total variance in
      suicidality. Apparently in unscreened college students, survival and coping
      beliefs and hope rather than hopelessness or other reasons for living are most
      related to suicidality. An implication is that facilitating college students'
      hopefulness may bolster their survival and coping beliefs and discourage
      development of suicidal thoughts or actions.

PMID- 7809318
TI  - Belief in and use of a questionable technique, facilitated communication, for
      children with autism.
AB  - 23 educators and therapists of children with autism were surveyed about their
      beliefs and use of Facilitated Communication, a technique previously shown to
      have questionable scientific validity. 65.2% or 15 use the procedure often or
      very often in their work with children. Some factors that appeared related to
      this choice were beliefs consistent with those of proponents of Facilitated
      Communication, less education, belief in the notion that individuals with autism
      were more intelligent than their behavior indicated, and lack of belief in
      science as a source of explanation of human behavior. It was concluded that
      supervisors need to be more informing about the scientific validity of techniques
      used by their employees.

PMID- 7809319
TI  - Depressed mood and early memories: some negative findings.
AB  - The study concerns the relation of scores on the Beck Depression Inventory and
      reports of memories for (a) the first three years of life and (b) ages 4 to 6 for
      a sample of 208 university undergraduates. While there was a tendency for the
      entire sample to characterize early memories as pleasant as opposed to
      unpleasant, no correlation was found between Beck scores and the tendency to
      characterize early memories as unpleasant.

PMID- 7809320
TI  - Maximizing heritability of a linear combination of traits.
AB  - In 1971 Jones proposed an approximate procedure for finding that linear
      combination of scores which has maximum heritability in a twin sample. I give an
      exact small-sample procedure. I point out two problems: such procedures can over
      optimize the heritability by capitalizing on chance, and confidence intervals and
      significance tests are needed. I give an approach using James-Stein shrinkage
      estimation and bootstrapped standard errors to address these problems. It appears
      that confidence intervals may be quite broad. To reduce the width of the
      confidence intervals, one can accept some small-sample bias in exchange for
      smaller sampling errors. The James-Stein approach to estimating coefficients is
      used to achieve reduced confidence interval width. I illustrate with a
      computational example using personality data.

PMID- 7809321
TI  - Social comparisons of learning disabled and nonexceptional adolescents.
AB  - 36 learning disabled high school subjects rated themselves lower on academic,
      psychomotor, and verbal performance on a social comparisons task than a control
      group of 53 nonexceptional peers. Learning disabled students tended to see
      themselves as less able in most areas involving school achievement but not in
      areas involving extracurricular activities.

PMID- 7809323
TI  - Marital distress across the mid-life transition among middle-class Caucasian
      women.
AB  - Aspects of Levinson's 1978 theory of adult development were used to examine
      women's progress across the mid-life transition. The subjects were 126 married,
      Caucasian mothers, ages 37 to 47 years. Contrary to prediction, age-related
      differences in marital distress were not found. For the sample as a whole,
      marital distress was related to a family history of distress, difficulty in
      parent-child relations, and inequitable task-sharing with spouses. Some of the
      difficulties for women in combining family and career within the context of
      current social and family structures are discussed.

PMID- 7809322
TI  - Early intervention for preschoolers with developmental delays: the case for
      increased child collaboration.
AB  - In this article are analyzed the four following premises that explain why early
      intervention programs for preschool children with mental retardation (and other
      disabilities) have tended to adopt a teacher-directed "cultural transmission" or
      remedial model of education, whereas preschool programs for children without
      disabilities have generally preferred a more child-directed "developmental"
      model. (1) The purpose of early intervention is to accelerate and remediate,
      rather than support, cognitive growth. (2) Learning and accountability are
      maximized by specific instructional objectives written into educational plans
      rather than by encouraging children's own constructivist efforts. (3) Children
      with retardation are defective, not just slow but otherwise normal and so require
      extensive adult direction. (4) Research findings are favorable rather than
      ambiguous towards demonstrating the effectiveness of existing instructional
      methods. The four premises are reviewed and critiqued. It is concluded that there
      is sufficient doubt about the cultural transmission remedial model to justify
      further expansion of the developmental approach in early intervention programs,
      at least for some children in some areas. Changes in attitudes and practices that
      such an expansion would entail are discussed.

PMID- 7809325
TI  - Geophysical variables and behavior: LXXVIII. Lunar phase and birthrate: an
      update.
AB  - Martens, Kelly, and Saklofske in 1988 examined 21 studies considering the
      possible relationship between lunar periodicities and birthrate. They reported
      that the majority of studies uncovered no relationship and that the positive
      studies were inconsistent in their findings. The present update reports on six
      additional studies on birthrate and lunar periodicities from five different
      countries. None of these studies produced evidence of lunar periodicities
      consistent with folklore or some previous studies.

PMID- 7809324
TI  - Mental health values of clergy: effects of open-mindedness, religious
      affiliation, and education in counseling.
AB  - Multivariate analyses of variance indicated that both religious affiliation and
      education in counseling of 44 Episcopal and 51 Catholic clergy had over-all
      effects on their scores on the Mental Health Values Questionnaire. In separate
      univariate analyses, significant effects were found on six of eight mental health
      value subscales. On all subscales in which significant interactions occurred,
      much of the variance was found among the clergy who were least well educated in
      counseling. As education in counseling increased, perceptions of mental health
      values became more consistent between affiliations. Mental health values of
      clergy were similar to those of a sample of psychotherapists, with Self
      acceptance and Good Interpersonal Relations being the highest scored values for
      both groups.

PMID- 7809326
TI  - Revised NEO Personality Inventory profiles of narcissistic and nonnarcissistic
      people.
AB  - This study investigated the construct validity of the Narcissistic Personality
      Inventory against the Revised NEO Personality Inventory to test the hypothesis
      that narcissistic and nonnarcissistic people have different personality profiles.
      The two inventories were administered to 96 male and 92 female undergraduates.
      Multivariate as well as univariate analyses of variance indicated that the
      Revised NEO Personality Inventory profiles were significantly different for
      narcissistic and nonnarcissistic groups which supported the construct validity of
      the Narcissistic Personality Inventory.

PMID- 7809327
TI  - Reliability and acquiescence in the measurement of locus of control with
      adolescents and adults with mental retardation.
AB  - The locus of control construct has been useful for explaining individual and
      group variability in motivation, personality, and achievement. Despite a general
      agreement that people with mental retardation generally lack control in their
      lives, the construct has not been used to any meaningful extent to explain less
      than optimal life outcomes experienced by this group. One reason that this
      circumstance exists is that people with mental retardation often answer questions
      in an acquiescent manner, thereby jeopardizing the reliability and validity of
      the measure. The present study examined the reliability of one measure of locus
      of control, the Adult version of the Nowicki-Strickland Internal-External Scale,
      for 491 adults and adolescents with mental retardation and, using alternative
      forms of this scale, assessed the extent to which acquiescence contributes to
      externality in this population. Results from repeated-measures analysis of
      variance suggest that the acquiescence contributes nominally to measurement error
      with this population. Suggestions are made to improve reliability with the scale.

PMID- 7809328
TI  - Myths about suicide in American and Philippine nurses.
AB  - 91 American student nurses were more accurate in their knowledge about suicide
      than 147 Philippine student nurses. However, the American nurses were incorrect
      on roughly 25% of the items on average, indicating that increased education about
      suicide would be of benefit to them.

PMID- 7809329
TI  - Preferences for religious or nonreligious counseling and psychotherapy.
AB  - Religious values in counseling and preferences for religious or secular
      counseling were investigated in two geographic areas. Over-all, 164 respondents
      distinguished religious from secular counseling and endorsed the importance of
      religious issues and the availability of counseling which can deal with religious
      issues. 51 preferred religious counseling. Small minorities expressed biases
      against religious or nonreligious counseling. Counseling preferences were based
      on the type of problem: religious counseling was preferred for marriage and
      family problems, and nonreligious counseling was preferred for mental illness and
      addiction, but religious and nonreligious counseling were equally chosen for
      depression. Frequency of church attendance was broadly related to preferences for
      religious and nonreligious counseling.

PMID- 7809330
TI  - Relationship of job stressors to job performance: linear or an inverted-U?
AB  - This study evaluated the potential positive effects of stressors on job
      performance by examining the shape of the relation between stressors and job
      performance. The 281 respondents were a demographically and organizationally
      heterogeneous group from the Detroit area, who were employed during the study.
      They were given four structured in-home interviews, approximately 6 weeks apart,
      over a period of 18 weeks. Interviews were also conducted with a significant
      other, nonminated by each respondent from work life. Stressors examined were role
      ambiguity, role conflict, and job insecurity. Strains, also examined as potential
      stressors, were job dissatisfaction, anxiety, depression, and anger. Technical
      and social aspects of respondents' job performance were measured separately, as
      were absenteeism and tardiness. All zero-order Pearson correlations were either
      statistically significant and in predicted directions or essentially zero. All
      relationships were monotonic, suggesting that, for these stressors, their optimal
      amounts are generally zero. Results are discussed in terms of arousal and
      activation, information-processing, and expectancy theory.

PMID- 7809331
TI  - Cognitive factors affecting abstinence among adolescent polysubstance abusers.
AB  - To examine cognitive variables in the maintenance of abstinence among
      polysubstance-abusing adolescents, analyses of data from 86 adolescents (31
      current users, 24 relapsers, and 31 abstainers) were done. Significant
      differences among these groups were found on a number of cognitive measures.
      Adolescents successful in maintaining abstinence possessed greater strategic
      knowledge and greater strategy-related self-efficacy. Further, adolescents who
      remained abstinent experienced greater reduction in their perceived risk of
      relapse when exposed to high-risk situations and experienced a corresponding
      increase in general expectation of enduring abstinence. An exploratory path
      analysis yielded some unexpected multivariate relationships. In particular,
      adolescents' knowledge of coping skills and strategy-related self-efficacy did
      not affect directly their expectations for continued abstinence. Instead,
      knowledge of coping skill and skill-related confidence appeared to function
      primarily to free the adolescent from perceptions of risk for relapse and only
      indirectly to enhance expectations of lasting sobriety.

PMID- 7809332
TI  - Suicide and unemployment: a monthly analysis.

PMID- 7809333
TI  - Aggressiveness revisited: a comment on Frank's "on the prediction of aggressive
      behavior from the Rorschach".

PMID- 7809334
TI  - Humanistic constructs and counseling homeless men.
AB  - The present humanistic model for counseling homeless men assumed that counseling
      goals evolve from each client's internal frame of reference and may include a
      positive adaptation to his homeless experience. The model encompasses Rogers'
      necessary components of psychotherapy, Sullivan's interpersonal theory of
      psychiatry, Adler's use of wellness and encouragement, and Privette's peak
      performance contribution. Factor analysis of history of homelessness, background
      data, ratings of subjective health and of happiness, and scores on Jones and
      Crandall's Short Index of Self-actualization yielded nine factors relevant to
      counseling. Empirical support was reported for placing a counseling services
      program in a multiservice facility for homeless persons.

PMID- 7809335
TI  - Theory, development, and interpretation of the CPI socialization scale.
AB  - The socialization (So) scale of the California Psychological Inventory is based
      partly on a role-taking or perspective-taking theory of social deviance and
      partly on the pragmatics of differentiating between more socialized and less
      socialized individuals. The theory, history, and current applications of the
      scale are reviewed, relationships to other scales and measures are examined, and
      the validity of the scale in arraying 69 male and 40 female samples along a
      putative continuum of socialization is evaluated. Finally, from these findings
      and from analyses of observers' adjectival and Q-sort descriptions significantly
      related to the scale, an interpretive psychology of the measure is propounded.

PMID- 7809336
TI  - Cognitive functioning in chronic fatigue syndrome and depression: a preliminary
      comparison.
AB  - This study used a brief battery of neuropsychological measures to examine the
      performance of patients with chronic fatigue syndrome (CFS) (N = 16) and patients
      in a major depressive episode (N = 23). The overall neuropsychological
      performance of the CFS group was not significantly different from depressed
      patients, and both groups scored within normal limits on most measures.
      Variability of neuropsychologic performance was in general unrelated to level of
      depressive symptoms. The results are discussed in terms of the validity of the
      cognitive criterion for the CFS diagnosis. Subjective complaints of cognitive
      dysfunction by CFS patients in light of the lack of objective evidence for the
      same are considered in terms of a somatic vigilance hypothesis.

PMID- 7809337
TI  - Detection of psychopathologic trends in glossodynia patients.
AB  - Glossodynia affects primarily middle-aged women. Although many possible
      etiologies have been proposed for the syndrome, most have not been substantiated.
      In the present study 56 glossodynia patients were evaluated for their
      psychopathologic profile as reflected by the SCL-90 questionnaire. The data show
      that glossodynia patients present a relatively high psychopathologic profile,
      especially on the scales of somatization and depression. Significant correlations
      were found between the intensity of pain experienced by the patients and some of
      the SCL-90 scales (somatization, depression, anxiety, GSI and PSDI). No
      correlations were found between SCL-90 scores and duration of symptoms,
      prevalence of symptoms per day and patient's condition during the past year.
      Patients living alone were found to differ significantly from those living with a
      significant other (overall group effect significant at the 0.01 level). The data
      suggest that psychopathologic trends may be associated with glossodynia.

PMID- 7809339
TI  - Family environment and glycemic control: a four-year prospective study of
      children and adolescents with insulin-dependent diabetes mellitus.
AB  - An onset cohort of children and adolescents with insulin-dependent diabetes
      mellitus (IDDM) and their parents were studied. Aspects of family environment
      were evaluated at study inception, and their influence on the initial level of,
      and change in, glycemic control over 4 years was examined. Family measures of
      expressiveness, cohesiveness, and conflict were linked to differences in the
      longitudinal pattern of glycemic control. In particular, the encouragement to act
      openly and express feelings directly (expressiveness) seemed to ameliorate
      deterioration of glycemic control over time in both boys and girls. Boys were
      especially sensitive to variations in family cohesiveness and conflict; those
      from more cohesive and less conflicted families showed less deterioration in
      glycemic control. This study demonstrated the important influence of family
      psychosocial factors present at diabetes onset on glycemic control in children
      and adolescents over the first 4 years of IDDM.

PMID- 7809340
TI  - Selective influence of menstrual cycle on perception of stimuli with reproductive
      significance.
AB  - Sixteen healthy women (20-32 years) not taking oral contraceptives were tested at
      three phases of their menstrual cycles (menses, preovulatory phase, and midluteal
      phase). Another 16 women taking oral contraceptives served as age-matched
      controls, and were tested during menses and during phases corresponding to the
      preovulatory and midluteal phase. On each test occasion, perception was assessed
      of visual stimuli belonging to three categories: sex (nude men), babies, and
      stimuli related to body care. Also, meaningless syllables were given. Stimuli
      were presented by a tachistoscope. Presentation of each stimulus was repeated
      until the subject signaled recognition. Trials to recognition and correctness of
      the recognition response were recorded. In spontaneously cycling women effects of
      the phase of the menstrual cycle depended on the stimulus meaning: During the
      preovulatory phase, there was an increase in the number of correctly recognized
      sex stimuli (p < 0.05) and of stimuli falsely recognized as sex stimuli (p <
      0.05). The number of stimuli falsely recognized as body care was reduced during
      this phase (p < 0.05). Moreover, during the luteal phase, the number of trials to
      recognition of baby stimuli was diminished (p < 0.01). In women taking
      contraceptives, no stimulus specific changes occurred, but correct recognition
      was generally improved during the luteal phase. Rather than supporting a general
      influence of the normal menstrual cycle on perceptual functions, the present
      results demonstrate that the effects of the menstrual cycle depend on the meaning
      of the stimulus with the perception of sexual stimuli, but not of stimuli related
      to maternal nurture, being improved during the preovulatory phase.

PMID- 7809338
TI  - Modernization in the Samoas and children's reactivity: a pilot study.
AB  - This investigation studied the potential effects of societal modernization on
      Samoan children's blood pressure and heart rate reactivity to a standardized
      television video game procedure. Ethnic Samoan children were sampled from Western
      Samoa (N = 72), a relatively underdeveloped country with a largely agricultural
      economy, and American Samoa (N = 70), a territory of the United States that has
      undergone substantial modernization due to recent economic aid. Results indicated
      that Western Samoans demonstrated significantly greater systolic blood pressure,
      diastolic blood pressure, and heart rate reactivity than American Samoans. These
      data, in conjunction with previous data, suggest that the hemodynamic effects of
      an acute stressor are inversely associated with societal modernization and an
      individual's adoption of a lifestyle reflecting integration into a modernized
      society. Further work is needed to examine the implications of this hypothesis
      and the associations among concrete measures of modernization and children's
      cardiovascular risk.

PMID- 7809341
TI  - Changes of opioid modulation of the hypothalamo-pituitary-adrenal axis in
      patients with severe premenstrual syndrome.
AB  - To assess the function of the hypothalamus-pituitary-adrenal axis in patients
      with severe premenstrual syndrome (PMS) 28 patients and 14 asymptomatic controls
      were studied during the mid- to late-luteal phase of the menstrual cycle. The
      response of plasma cortisol to both high-dose naloxone and corticotropin
      releasing hormone (CRH) was assessed. Naloxone stimulated a significant cortisol
      release in controls whereas it was otherwise almost absent in patients. CRH
      stimulated a greater release of cortisol in patients than in controls. Fifteen
      patients met criteria for either current anxiety and/or mood disorders. The
      cortisol secretion after both naloxone and CRH stimulations was similar for PMS
      patients with or without psychiatric disorders. These data indicate that
      endogenous opioids modulate the activity of the hypothalamus-pituitary-adrenal
      axis. Irrespective of the concomitant presence of menstrual migraine or
      psychiatric disorder, such control is altered in patients with severe PMS because
      of the possible hyposensitivity of opiate receptors. The hyperresponsiveness to
      CRH may be the consequence of the reduced inhibition that endogenous opioids
      tonically exert on HPA axis.

PMID- 7809342
TI  - Cognitive-behavioral and experiential group psychotherapy for HIV-infected
      homosexual men: a comparative study.
AB  - The knowledge of being infected with the human immunodeficiency virus type 1 (HIV
      1) brings about psychological distress and social problems including anxiety,
      depression, and social isolation. Participating in psychosocial intervention
      programs can help to reduce these problems. To date, however, very little is
      known about the efficacy of different intervention strategies. We implemented a
      study with a randomized experimental design to investigate the effectiveness of a
      cognitive-behavioral group psychotherapy (CBT) and an experiential group
      psychotherapy (ET) program for 39 asymptomatic HIV-infected homosexual men. Both
      therapies consisted of 17 sessions over a 15-week period. The major finding of
      this study was that psychosocial intervention, independent of the therapeutic
      orientation, decreased distress significantly, as compared with a waiting-list
      control group (WCG). There were no significant changes in the intervention groups
      as compared with the WCG in coping styles, social support, and emotional
      expression. Finally, CBT and ET did not differ in their effects on psychological
      distress or on the other psychosocial variables measured in this study.

PMID- 7809343
TI  - Psychosocial factors predictive of survival after allogeneic bone marrow
      transplantation for leukemia.
AB  - Previous research suggesting a link between psychosocial variables and survival
      after bone marrow transplant (BMT) has been limited by: a) retrospective
      assessment of psychosocial variables; and b) failure to concurrently examine a
      comprehensive set of disease, treatment, and demographic variables potentially
      related to post-BMT survival. The present study prospectively assessed
      psychosocial variables (depressed mood, functional quality of life, and mental
      adjustment to cancer) that have been linked to survival after BMT and/or
      malignant disease. Study participants (N = 42) received allogeneic BMT for either
      acute or chronic leukemia. Analyses using Cox proportional hazards regression
      indicated that quality of bone marrow graft match was the only disease,
      treatment, or demographic variable significantly associated with post-BMT
      survival (p = .05). Addition of psychosocial variables to a multivariate Cox
      regression model including quality of graft match suggested that an attitude
      toward cancer characterized by "anxious preoccupation" (p = .008), as well as
      poorer functional quality of life (p = .052), were each independently associated
      with poorer post-BMT survival. Further research is necessary to identify the
      mechanisms by which psychosocial variables could contribute to post-BMT survival.

PMID- 7809344
TI  - Effect of short-term cognitive psychotherapy on recurrence of duodenal ulcer: a
      prospective randomized trial.
AB  - The aim of this prospective, randomized trial was to assess whether short-term
      cognitive psychotherapy (10 sessions during 4 months) could reduce the 1-year
      recurrence rate of duodenal ulcer. One group received psychotherapy; one group
      was a control group. One hundred patients, aged 17 to 64 years, with duodenal
      ulcer were selected from March 1989 to May 1991. The main outcome measure was
      relapse of duodenal ulcer, which was verified by endoscopy. When psychotherapy
      started after cessation of antiulcer medication, the relapse-free time was
      significantly shorter in the therapy group than in the controls. When the
      protocol was modified so that psychotherapy and antiulcer medication were given
      concomitantly, there was no significant difference in recurrence rate between the
      groups at 1-year follow-up (84% in the therapy group and 92% in the control
      group). Symptoms of upper abdominal discomfort/pain, measured every second month,
      decreased significantly in the therapy group compared to the control group.
      Psychotherapy led to less neuroticism (Eysenck Personality Questionnaire) and
      less trait anxiety (Spielberger Trait Anxiety Scale) compared to controls at 4
      months. At the 12-month follow-up, most of this gain was lost, but the
      psychotherapy group had lower scores on "concern about disapproval" on the
      Sociotropy-Autonomy Scale than the control group. There is no beneficial effect
      of short-term cognitive psychotherapy on the 1-year recurrence rate of duodenal
      ulcer.

PMID- 7809345
TI  - Neuropsychological performance of young men who vary in familial risk for
      hypertension.
AB  - Neuropsychological performance was examined as a function of parental history of
      hypertension. Thirty-five normotensive offspring of two hypertensive parents
      (PH+/+) were compared to 35 offspring of two normotensive parents (PH-/-) and 35
      offspring of one hypertensive and one normotensive parent (PH+/-) on tests of
      abstract reasoning, attention/mental flexibility, memory, perception, psychomotor
      skills, and visuospatial/constructional abilities. Results indicated that PH+/+
      offspring performed more poorly than PH-/- offspring on tests of
      visuospatial/constructional and visuoperceptual ability; PH+/- offspring tended
      to score lower than PH-/- offspring on these tests. These findings were
      independent of age, education, diastolic blood pressure levels, average alcohol
      consumption, trait anxiety, and depression. Results of this study may indicate
      subtle central nervous system involvement associated with familial risk for
      hypertension.

PMID- 7809346
TI  - Alexithymia and repression: contrasting emotion-focused coping styles.
AB  - A number of conceptually similar emotion-focused coping styles have been related
      to physical well-being. We assessed the relationship between two of these
      constructs, alexithymia and repressive coping, on the basis of both psychometric
      and psychophysiological comparisons. Questionnaires were used to classify 86
      healthy female subjects as low anxious, high anxious, or repressors. These
      subjects then completed a self-report measure of alexithymia and participated in
      a stressful laboratory task in which they delivered a self-disclosing speech.
      Emotional response patterning was assessed by comparing self-reported negative
      affect to heart rate responses elicited during the stressful speech task. Results
      indicated that the alexithymia scores of high anxious subjects were significantly
      greater than those of repressors. Consistent with the psychometric data, high
      alexithymics exhibited an emotional response pattern characteristic of high
      anxious subjects (self-reported negative affect greater than heart rate), whereas
      low alexithymics exhibited a response pattern characteristic of repressors (heart
      rate greater than self-reported negative affect). The results suggest that
      alexithymia and repressive coping are quite distinct, with repression being more
      similar to low alexithymia than to high alexithymia.

PMID- 7809347
TI  - Health complaints and outcome assessment in coronary heart disease.
AB  - Research on coronary heart disease (CHD) lacks sensitive outcome measures. Health
      complaints, although subjective in nature, may provide information on the degree
      of recovery from CHD. The purpose of Study 1 was to identify common health
      complaints in a group of 535 men (mean age, 57.5 years) with CHD. In the weeks
      after a coronary event, they frequently reported somatic (e.g., chest pain,
      dyspnea, fatigue, sleep problems) and cognitive (e.g., concern about health and
      functional status) health complaints. Statistical analyses produced the Health
      Complaints Scale (HCS), which comprises 12 somatic and 12 cognitive complaints.
      Confirmatory factor analysis provided evidence for the model undergirding the
      HCS, and the somatic and cognitive scales of the HCS were found to have high
      internal consistency (alpha > or = .89), adequate test-retest reliability (r > or
      = .69), and good construct validity. Study 2 provided evidence for the idea that
      the HCS can be distinguished from standard scales of psychopathology. Statistical
      analyses in 266 men with CHD indicated that, compared to symptoms of
      psychopathology, the HCS scales displayed discrete factor loadings as well as
      higher scores at baseline and a normal clustering of scores. Important to note,
      HCS scores decreased in 60 subjects participating in cardiac rehabilitation (p <
      .0001) but not in 60 control subjects. Although research should not disregard
      psychological biases on symptom reporting, it is argued that health complaints
      need to be accurately assessed in CHD patients.

PMID- 7809348
TI  - [Psychosomatic medicine--the future of an illusion].
AB  - This paper presents the phenomenology and the development of theories about
      alexithymia, a "behavioral neurosis" in psychosomatic patients, with background
      of the american (F. Alexander, R. Grinker and P. Knapp) and french (P. Marty)
      psychosomatic schools. Luminet's understanding comprises the combination of an
      object-relations-theory perspective of alexithyma with the clinical theory of
      "depression essentielle" of Marty. Primary and secondary shortcomings and
      dysregulations in the early mother-child-relation lead to essential insecurity in
      building up stable self and object representations with a specifically reduced
      libidinal tonus of the self and dependency of objects. These conditions lead to
      the formation of alexithymic disturbances in thought, interaction and object
      relations, as well as to impaired capacity for self reflection in perception and
      evaluation of affects, which do not become available as signals for the ego
      functions. Moreover, as the capacity for self regulation, as a function of
      maternal care, could not be internalized, there is an increased proneness for
      somatisation. In literature, these characteristics were commonly taken for the
      main limitations for the success of psychoanalytic or psychodynamic treatments.
      Luminet's psychotherapeutic access in the treatment of alexithymic patients is
      based on activation and differentiation of the self and object representations
      through verbal and nonverbal techniques, aiming on actualisation and development
      of maternal functions; this implies the acknowledgement of the physical body
      within the therapeutic relationship and awareness of specific counter
      transference reactions.

PMID- 7809349
TI  - [Psychosomatic medicine in the general hospital: problem spectrum in a random
      sample of 100 internal medicine patients].
AB  - The psychosocial problems of a random sample of 100 patients in a medical
      department of a general hospital have been explored. About 15 to 20% of these
      patients suffered from terminal illness. About half of the patients felt
      physically and emotionally severely stressed. Besides the illness itself problems
      resulting of their life situation were the most important stressors, especially
      difficulties in family or partnership, loneliness and suicidal trends.
      Psychosocial factors seemed to influence the illness or the decision for hospital
      treatment at about 2/3 of the patients, at 21% this could be clearly concluded
      from the diagnosis made at the end of hospital treatment, mostly concerning
      alcoholism. Coping problems were found at 12 to 26% of the patients. The demands
      for psychosomatic treatment are high in general hospital, they differ much from
      those in specialized psychosomatic institutions.

PMID- 7809350
TI  - [Effect of the setting on therapeutic verbalization of affects].
AB  - In psychotherapy research vocabulary measures are still an exception, although
      clinically relevant hypotheses might well be investigated by means of those
      measures. The affective vocabulary seems to be particularly apt to serve as an
      indicator of psychotherapeutic processes, since the "processing of emotions" can
      be regarded as a crucial part of any kind of psychotherapy. The emotion theory of
      Dahl and a classification schema derived from DeRivera will be explained in the
      text. The development of the Affective Dictionary Ulm (ADU), a computer measure
      for evaluation of affective vocabulary was based on this classification system.
      The distinction between two important categories of emotions, it-emotions (like
      anger) referring to wishes about objects, and me-emotions (like depression)
      reflecting self states, i.e. beliefs about the status of wish fulfillment, will
      be explained. The study described focuses on the affective vocabulary of one
      psychotherapist in three different settings: initial interviews, short term
      therapy and psychoanalysis. It can be demonstrated, that the "intensity" of the
      setting significantly positively correlates with the use of words indicating
      object (or it-) emotions. According to the transference paradigm, these results
      suggest, that the intensification of psychodynamic settings lead to an increasing
      work on help to regulate object relationships.

PMID- 7809351
TI  - [Which patients benefit from treatment with respiratory feedback?].
AB  - The physiological and psychological data of 82 patients with essential
      hypertension, who participated in the treatment group of a respiratory feedback
      (RFB) evaluation (Franck et al. 1994), were examined, using clusteranalysis, to
      detect and to describe therapy responders and nonresponders. For patients with
      usual personality characteristics, active coping strategies and interest in games
      and technics the best blood-pressure decrease (systolic bp: 13.05 mmHg, diastolic
      bp: 10.63 mmHg) was found. Furthermore patients, who stopped RFB-treatment have
      been compared with patients, who finished the treatment program. Patients, who
      stopped the RFB-treatment, had more psychological symptoms in the sense of
      psychosomatic complaints.

PMID- 7809353
TI  - The medical-psychiatry unit. A pilot study of conjoint care within an Irish
      general hospital.
AB  - The establishment of medical-psychiatry units within the general hospital is an
      important advancement for psychiatry and has met with favorable response within
      the American health care system. A brief account is given here of the piloting of
      such a unit within an Irish hospital, and the merits of this strategy are
      discussed.

PMID- 7809352
TI  - [Social support by professional personnel during inpatient treatment of cancer
      patients. "Chronic disease and coping with illness" research project].
AB  - We examined 63 in-patients in a medical hospital with a semi-structured and video
      taped interview about the professional social support they had received. Patients
      were quite satisfied with physicians' and nurses' support, still more than one
      third of them had missed appraisal support from physicians. We found evidence
      that older, more ill and female patients perceived more professional social
      support was given. With the help of a hierarchical cluster analysis it was shown
      that the importance of professional social support depended remarkably on
      individual factors as identity or partner relation.

PMID- 7809354
TI  - Social phobia secondary to physical disability. A review of benign essential
      tremor (BET) and stuttering.
AB  - Persons with physical disabilities cannot be diagnosed as having social phobia
      under current DSM-III-R criteria. The DSM-III-R social phobia diagnosis excludes
      persons where a physical disorder causes the distress and phobic avoidance.
      However, the authors have noted in clinical practice that social phobia and
      physical disabilities sometimes coexist. A review of the published literature
      reveals that stutterers and BET patients frequently have social phobia-like
      symptoms. No prevalence data on comorbid DSM-III-R-defined social phobia were
      found in these groups (i.e., social phobia occurring in areas where the
      disability does not cause the distress and avoidance). Further research is
      warranted to determine the prevalence of social phobic behaviors occurring in
      conjunction with certain physical disabilities.

PMID- 7809355
TI  - An interdisciplinary group for parents of children with hemangiomas.
AB  - Parents are shocked by the unexpected appearance and growth of hemangiomas, the
      most common benign tumors of childhood, yet parents' psychosocial needs are
      largely ignored. A psychoeducational/self-help pilot group for parents is
      described in this article. The Mental Health Inventory and a 44-item
      questionnaire were used to gather pertinent biopsychosocial data. Parents were
      more distressed and had less of a sense of well-being than the general
      population. Medical complications were significantly associated with the couple's
      distress (P < 0.05). Parental perception of hemangiomal surface area or site was
      not correlated with parental distress. Therapists clinically assessed parental
      distress, presented coping strategies for parents and families, and discussed
      medical information about hemangiomas and normal childhood development.

PMID- 7809356
TI  - One-year follow-up of medical outpatients with hypochondriasis.
AB  - To examine the diagnostic stability and outcome of hypochondriasis, the authors
      followed 50 patients with this disorder and 50 age- and sex-matched control
      subjects after 1 year. After 1 year, two-thirds of the subjects continued to meet
      criteria for hypochondriasis, and the remaining third had persisting
      hypochondriacal symptoms. The hypochondriacal subjects were improved on most
      measures but still differed from the control subjects with regard to attitudes,
      perceptions, and behaviors that had distinguished them initially. More severe
      symptoms, longer duration of illness, and coexisting psychiatric illness were
      predictive of a worse outcome. The data indicate that the diagnosis of
      hypochondriasis is stable over time, and that, although symptoms wax and wane,
      characteristic features persist. The findings underscore the importance of
      diagnosing and treating hypochondriasis in medical outpatients.

PMID- 7809357
TI  - Severity of somatization and its relationship to psychiatric disorders and
      personality.
AB  - Medical patients' (75 with chronic fatigue complaints, 61 with dizziness, and 88
      with disabling tinnitus; N = 224) current and past psychiatric diagnoses and
      personality characteristics were assessed to determine if they could
      independently explain the number of medically unexplained physical symptoms that
      the patients had experienced. Cloninger's Tridimensional Personality
      Questionnaire (TPQ) and the Diagnostic Interview Schedule based on DSM-III-R were
      used to assess the personality and psychiatric diagnoses, respectively. The
      results revealed that the number of lifetime medically unexplained symptoms were
      significantly, independently, and positively related to increasing numbers of
      current and past anxiety and depressive disorders and to the harm avoidance
      dimension of the TPQ. In a second analysis, the "worry/pessimism" and
      "impulsiveness" subscales were positively related to the number of medically
      unexplained symptoms. The results suggest that somatization is associated with
      current and past history of psychiatric illnesses and harm avoidance in this
      sample of medical patients.

PMID- 7809358
TI  - Frequency and correlates of adjustment disorder related to cardiac surgery in
      older patients.
AB  - The diagnosis of adjustment disorder is a dilemma in older medically ill
      patients. The authors conducted a prospective study of older cardiac surgery
      patients. Semistructured interview techniques were used to distinguish emotional
      impairment from physical impairment to diagnose an adjustment disorder. Among 71
      patients interviewed at three points in time, 50.7% had an adjustment disorder.
      At 6 months after surgery, 30.6% were still showing evidence of emotional
      functional impairment. Continued impairment was related to initial severity of
      depressive and anxiety symptoms. Implications and suggestions for future research
      are discussed.

PMID- 7809359
TI  - The relationship of psychosomatic medicine to consultation-liaison psychiatry.
AB  - Consultation-liaison psychiatry arose in the mid-1960s from the matrix of
      psychoanalytically oriented psychosomatic medicine. The influence of
      psychoanalysis and psychoanalytically trained academic psychiatrists gradually
      waned. The liaison aspect of consultation-liaison psychiatry faded in the early
      1980s, and most consultation-liaison services are now primarily high-quality
      consultation services that contribute much to university teaching hospitals. The
      consultation-liaison service at the University of New Mexico (UNM) and several
      others have eliminated the term "liaison." The consultation service at UNM sees
      relatively few patients with classic psychosomatic disorders. The majority of
      requests to UNM's consultation service relate to suicide attempts, delirium,
      complicated medical problems with psychiatric illness, substance abuse, burns,
      trauma, and competency evaluations.

PMID- 7809360
TI  - Suicide in liver transplant patients.

PMID- 7809361
TI  - Factitious hermaphrodism.

PMID- 7809362
TI  - New-onset narcolepsy and paroxetine.

PMID- 7809363
TI  - Somatization disorder by proxy.

PMID- 7809364
TI  - Radially restricted linear energy transfer for high-energy protons: a new
      analytical approach.
AB  - Radially restricted linear energy transfer (LET) is a basic physical parameter
      relevant to radiation biology and radiation protection. In this report a
      convenient method is presented for the analytical computation of this quantity
      without the need for complicated simulation. The method uses the energy
      restricted LET L delta, as recently redefined in a 1993 ICRU draft document and
      supplements it by a relatively simple term that represents the energy of fast
      delta rays lost within distance r from the track core. The method provides a
      better fit than other models and is valid over the entire range of radial
      distance from track center to the maximum radial distance traveled by the most
      energetic secondary electrons. Lr computed by this approach differs only a few
      percent from the values obtained from explicit Monte Carlo simulations. The
      concept applies equally to heavy ions and to electrons.

PMID- 7809365
TI  - Hits to bone cell nuclei from nonuniform radioactive labels.
AB  - The stochastic aspects of alpha-particle traversals through nuclei of bone-lining
      cells from nonuniform radioactive labels are worked out. Both the residence time
      of the target and the hit rate are considered random variables. It is shown that
      with any type of bone remodeling the fraction of cells not hit increases with
      increasing nonuniformity of the label concentration. Thus, a completely uniform
      concentration represents the most dangerous situation. A possible negative
      correlation between residence times and hit rates, observed in some experiments,
      tends to decrease the probability of alpha-particle hits. As a practical
      application, the theory is applied to the International Commission on
      Radiological Protection model of the distribution of 239Pu in the human body. In
      the case of 50 years of chronic ingestion of 1 annual limit of intake (ALI) per
      year for class W and chronic inhalation of 1 ALI/year for class Y compounds, more
      than 19.4 and 8.5% of the nuclei of bone-lining cells are traversed by at least
      one alpha-particle, respectively.

PMID- 7809366
TI  - Similarities between human ataxia fibroblasts and murine SCID cells: high
      sensitivity to gamma rays and high frequency of methotrexate-induced DHFR gene
      amplification, but normal radiosensitivity to densely ionizing alpha particles.
AB  - Two gamma-ray hypersensitive cell lines, human ataxia telangiectasia (AT) and
      murine severe combined immune deficiency (SCID) cells, proved to be very
      competent in amplifying their dihydrofolate reductase (DHFR) gene under
      methotrexate selection stress. Over a period of months, methotrexate-resistant
      clones were obtained which were able to grow in progressively increasing
      methotrexate concentrations up to 1 mM. By then methotrexate-resistant AT and
      SCID cells had amplified their DHFR gene 6- and 30-fold, respectively, and showed
      very high DHFR mRNA expression. In contrast, related cells with normal
      radiosensitivity (human GM637 and mouse BALB/c fibroblasts) did not show DHFR
      gene amplification under comparable conditions. This correlation of the capacity
      of DHFR gene amplification and gamma-ray hypersensitivity in AT and SCID cells
      suggests that gene amplification may have a mechanism(s) in common with those
      involved in repair of gamma-radiation-induced damage. No difference in cell
      killing could be observed following exposure to densely ionizing alpha particles:
      AT and SCID cells exhibited comparable survival rates to GM637 and BALB/c cells,
      respectively.

PMID- 7809367
TI  - Adaptive response to mutagenesis and its molecular basis in a human T-cell
      leukemia line primed with a low dose of gamma-rays.
AB  - The effect was studied of a low dose of gamma-ray preexposure on the frequency
      and molecular spectrum of radiation-induced mutations at the hprt locus in a
      human T-cell leukemia line. When the cells were preexposed to 0.01 Gy of gamma
      rays, the yield of mutations induced by a subsequent 2-Gy challenge dose was
      reduced by 60%, compared with the 2 Gy of irradiation alone. The data of Southern
      blot analysis showed that 47% of the mutants induced by 2 Gy in the cells without
      low-dose preexposure were of the deletion or rearranged mutations type. In
      contrast, in the low-dose radioadapted cells the proportion of this type of 2-Gy
      induced mutations decreased to 28%. This is close to the control level (22%) of
      spontaneous mutations. Our results confirm that a low dose of gamma-ray
      preexposure leads to a decreased susceptibility to gene deletions and
      rearrangements after high-dose irradiation.

PMID- 7809368
TI  - Evaluation of spermatogenic response of mice to the induction of mutations by
      combined treatment with X rays and antineoplastic drugs.
AB  - Combined treatment with low doses of X-rays plus cyclophosphamide (0.25 Gy + 25
      mg/kg body weight) or X-rays plus mitomycin C (0.25 Gy + 1.75 mg/kg body weight)
      did not induce significant dominant lethal effects in any stage of
      spermatogenesis when a parameter representing pre- and postimplantation loss,
      such as the decrease of live implants per female, was applied. After combined
      exposure to high dose of X-rays plus cyclophosphamide (1.00 Gy + 100 mg/kg body
      weight) an increase of dominant lethal mutations (DLMs) was observed in
      differentiating spermatogonia, spermatids, and spermatozoa with the same
      parameter. Combined treatment with high doses of X-rays plus mitomycin C (1.00 Gy
      + 5.25 mg/kg body weight) produced DLMs in differentiating spermatogonia and late
      spermatocytes. A calculation of "enhanced risk" was applied to the data of DLMs
      from the combined treatment regimen and was based on the proportion of dead
      implants (postimplantation loss only). Enhanced risk could be shown not only
      after high but also after low combined exposure to X-rays plus cyclophosphamide
      and X-rays plus mitomycin C. With low doses this enhanced risk was observed in
      spermatids for X-rays plus cyclophosphamide and in differentiating spermatogonia
      to early spermatocytes for X-rays plus mitomycin C.

PMID- 7809369
TI  - Heavy ion induced membrane damage: hemolysis of erythrocytes and changes in
      erythrocyte membrane fluidity.
AB  - Human erythrocytes were irradiated with heavy ions of energies between 4 and 18
      MeV/u having linear energy transfer (LET) values between 92 and 14,000
      keV/microns. Hemolysis has been studied as a macroscopic parameter for membrane
      damage and changes of the fluidity as a more microscopic parameter. The membrane
      fluidity changed in a characteristic dose-dependent manner as detected by
      electron spin resonance employing 12-doxylstearic acid methyl ester spin label
      (SL 12). Lysis cross sections and RBE values were determined from dose effect
      curves. The results demonstrate a high hemolytic efficiency of heavy ions
      compared to X rays. With increasing LET values the measured relative biological
      efficiency (RBE) values increase continuously. In the complete LET range the
      cross sections formed one common curve as function of LET and no saturation
      effects are observed. This is in direct contrast to other biological endpoints
      such as cell inactivation or DNA damage.

PMID- 7809370
TI  - Influence of stable iodine on the transfer of 131I into cows' milk.
AB  - The effect of supplying three different stable iodine levels (about 70, 80, and
      160 mg day-1) in the daily feed of four dairy cows has been studied for the
      excretion pattern of 131I. None of the different treatments had a statistically
      significant effect. A mean milk transfer coefficient of 0.015 +/- 0.001 d l-1 was
      determined for all iodine supply levels investigated.

PMID- 7809372
TI  - The growth of fractal humic acids: cluster correlation and gel formation.
AB  - The growth of humic acids, prepared by a gentle method from two different kinds
      of soils (I and II), has been studied using small-angle neutron scattering at an
      acidity corresponding to pH 5.0 and 0.10 M ionic strength (NaCl). Humic acids
      aggregate either to large clusters with a fractal dimension of 2.3 and an average
      diameter of 1720 A (I) or to clusters with an average diameter of 700 A (II).
      After storage for 2 days at 4 degrees C, the latter aggregates (II) formed a gel.
      In a step toward gelation, we observed cluster-cluster interaction from the
      neutron-scattering data in the form of a correlation peak. These differences in
      size can be explained by assuming that the smaller particles (II) are trapped
      into a nonequilibrium state characterized by the temperature-solvent condition.
      The importance of a humic acid gel network for the conservation of water and
      nutrients in the environment is discussed.

PMID- 7809371
TI  - Attenuation effects on the kerma rates in air after cesium depositions on
      grasslands.
AB  - Since the reactor accident of Chernobyl, cesium depth profiles and nuclide
      specific kerma rates in air have been determined for various grassland sites in
      south Bavaria and in Ukraine. The sites are described by soil characteristics,
      annual precipitation, distance from release point, mode of deposition, and
      activity per unit area. The effects of surface roughness and migration of cesium
      into the soil on the kerma rate in air over grasslands was determined by two
      methods. The kerma rates in air obtained by the evaluations of in situ gamma-ray
      spectrometry results and of measured activity distributions in the soil showed
      only negligible differences for the observation period of 6 years after
      deposition. For the sites in Ukraine the kerma rate in air per activity per unit
      area was found to be systematically 40% higher than in Bavaria. The results from
      Bavaria on the attenuation of the kerma rate and a data set, including
      experiences from the weapons test fallout, are analytically approximated as a
      function of time up to 25 years after deposition.

PMID- 7809373
TI  - [Remembrance of things past: a career in a chiroptical work].

PMID- 7809374
TI  - [Activation mechanism of neutrophil NADPH oxidase complex--molecular pathology of
      chronic granulomatous disease].

PMID- 7809375
TI  - [Transferrin--structure and cooperativity on metal-binding].

PMID- 7809376
TI  - [Molecular mechanisms of learning and memory in classically conditioned
      molluscs].

PMID- 7809378
TI  - [Fibronectin type III-like domains found in prokaryotic proteins and protein
      evolution].

PMID- 7809377
TI  - [Fluorescence-labeled bio-active compounds].

PMID- 7809379
TI  - [A method for selective isolation of amino-terminal peptide from alpha-amino
      blocked proteins].

PMID- 7809380
TI  - Effects of U46619 and of inhibitors of the synthesis of TXA2 on insulin action on
      the metabolism of labelled glucose in uteri isolated from ovariectomized-diabetic
      rats.
AB  - The production of 14CO2 from labelled glucose by isolated uterine strips from
      ovariectomized-diabetic rats has been studied. U46619, an analogue of TXA2 did
      not affect basal glucose metabolism; however, insulin-induced increment in CO2
      production was completely blocked, both in ovariectomized (OVD) or ovariectomized
      estrogenized (OVED) diabetic uterus. OKY064 as well as UK38485, both inhibitors
      of TXA2 synthesis, stimulated glucose metabolism (p < 0.05) similar to that of
      insulin in uterine tissue from OVD and OVED rats. Inhibition in the synthesis and
      release of TXB2 was detected (p < 0.01) by uterine radioconversion of 14C
      arachidonic acid when adding OKY38485 to the incubation medium, and the
      production of other prostanoids such as 6-keto-PGF1 alpha, PGF2 alpha and PGE2
      was enhanced. In summary, TXA2 inhibited insulin-induced glucose metabolism in
      diabetic animals.

PMID- 7809381
TI  - Effects of prostaglandin F2 alpha (PGF2 alpha) on secretion of estradiol-17 beta
      and cortisol in 90 to 100 day hysterectomized, intact and ovariectomized pregnant
      ewes.
AB  - Vehicle or 8 or 16 mg PGF2 alpha/58 kg/body weight (BW) was given intramuscularly
      to intact, hysterectomized and ovariectomized 90 to 100 day pregnant ewes in
      three separate experiments. Hysterectomy alone decreased (P < or = 0.05)
      estradiol-17 beta in jugular venous blood by 80 percent within 16 hours and
      profiles of estradiol-17 beta did not differ (P > or = 0.05) among vehicle or 8
      or 16 mg PGF2 alpha/58 kg/BW-treated ewes. Profiles of estradiol-17 beta differed
      (P < or = 0.05) in intact pregnant ewes treated with 8 or 16 mg PGF2 alpha/58
      kg/BW when compared to controls and in ovariectomized (P < or = 0.10) 90 to 100
      day pregnant ewes treated with 16 mg PGF2/58 kg/BW. Estradiol-17 beta decreased
      (P < or = 0.05) over time in vehicle and 8 mg PGF2 alpha/58 kg/BW-treated intact
      and in vehicle-treated ovariectomized 90 to 100 day pregnant ewes. Cortisol
      decreased (P < or = 0.05) over time in hysterectomized, intact, and
      ovariectomized 90 to 100 days pregnant ewes, but did not differ (P < or = 0.05)
      among vehicle or 8 or 16 mg PGF2 alpha/58 kg/BW-treated ewes. It is suggested
      that estradiol-17 beta has a role in regulating ovine placental steroidogenesis.

PMID- 7809382
TI  - Effects of acute exercise on the changes of lipid profiles and peroxides,
      prostanoids, and platelet activation in hypercholesterolemic patients before and
      after treatment.
AB  - The effects of acute exercise on the changes of plasma lipid profiles and
      peroxides, prostanoids and platelet activation in hypercholesterolemic patients
      before and after pravastatin 5 mg twice daily treatment for 4 weeks was studied
      in 30 (M/F = 21/9, age = 52 +/- 7, Mean +/- SD) patients with plasma total
      cholesterol level > 240 mg/dl. Pravastatin significantly reduced plasma total and
      low density lipoprotein cholesterol levels as expected. All patients before and
      after treatment and 30 healthy controls performed a treadmill exercise test using
      the standard Bruce protocol. The cardiac performance was similar in all groups.
      Treadmill exercise did not influence lipid levels after plasma volume correction.
      Hypercholesterolemic patients had significantly higher pre-exercise levels of
      malondialdehyde, thromboxane beta 2 and beta-thromboglobulin than after treatment
      or than pre-exercise levels in the control group. Treatment with lipid lowering
      drug pravastatin lowered the levels of these three parameters. At peak exercise,
      superoxide dismutase activity and 6-keto-PGF1 alpha were elevated. At 10 min post
      exercise only malondialdehyde returned to pre-exercise levels. The superoxide
      dismutase, thromboxane B2 and beta-thromboglobulin remained significantly higher.
      In the control subjects plasma beta-thromboglobulin and thromboxane 2 returned to
      pre-exercise levels. These results suggest that hypercholesterolemia may induce
      lipid peroxidation and platelet activation in resting status. Lowering of plasma
      cholesterol of pravastatin causes a concomitant decrease in plasma
      malondialdehyde, thromboxane and beta-thromboglobulin suggesting a decrease in
      lipid peroxidation and platelet activation. These changes were more pronounced in
      the hypercholesterolemic patients. Pravastatin treatment attenuated the increase
      in both malondialdehyde, beta-thromboglobulin and the prostanoids, but not to the
      level of normal subjects.

PMID- 7809383
TI  - Decrease in human plasma gravidin levels after medical abortion.
AB  - The aim of this study was to determine if loss of pregnancy is associated with a
      decrease in plasma levels of gravidin, a phospholipase inhibitor thought to
      maintain pregnancy. Blood was taken from 28 women in the first trimester of
      pregnancy who had requested an abortion. The progesterone receptor antagonist, RU
      486 was given on Day 0 for termination of pregnancy. Plasma gravidin levels were
      measured on day 0 and on day 2 just before the patients were given misoprostol, a
      prostaglandin E1 analogue (600 micrograms). In a small group of patients, plasma
      measurements were continued up to 42 days. By day 2, plasma gravidin levels had
      fallen significantly (100% to 94%, p = 0.010 in a paired t-test). Following
      treatment with prostaglandins and pregnancy loss, plasma gravidin levels
      continued to fall until day 14 when the non pregnant level was reached at 80% of
      the pregnant level. We conclude that a decrease in plasma gravidin levels is
      associated with loss of pregnancy. This may occur because progesterone action is
      blocked.

PMID- 7809384
TI  - Suppression of acute inflammation with liposome associated prostaglandin E1.
AB  - Prostaglandin E1 (PGE1) suppresses leucocyte effector function and reduces
      inflammation in several animal models of acute and chronic inflammation. A
      drawback to its use as a therapeutic agent is the relatively high doses needed to
      suppress inflammation. We present evidence in this report that liposome
      associated PGE1 (LAP) reduces markedly acute inflammation induced in a
      subcutaneous air pouch by monosodium urate crystals, and by the polypeptide
      mediators, interleukin 1-beta (IL-1 beta) and tumor necrosis factor alpha (TNF
      alpha). A single dose of 12 micrograms/kg LAP given intravenously 2 hr after
      inflammation was induced, reduced accumulation of cells and exudate by 31-49%.

PMID- 7809385
TI  - Polarized release of lipid mediators derived from phospholipase A2 activity in a
      human bronchial cell line.
AB  - The release of arachidonic acid (AA) and platelet activating factor (PAF) from
      airway epithelial cells may be an important mediating factor in lung
      physiological and inflammatory processes. The type of lung response may be
      determined by the directional release of AA and PAF. We used the human bronchial
      epithelial cell line, BEAS2B (S6 subclone; BEAS), to investigate the polarized
      release of AA and PAF from lung epithelial cells. BEAS, grown on Transwell
      filters, were prelabeled with either 3H-AA or 3H-lyso-PAF. 3H-AA products and 3H
      PAF were analyzed by high performance liquid chromatography and thin layer
      chromatography, respectively. BEAS incubated with melittin (2-4 micrograms/ml for
      15 min) had an increased release (compared to vehicle-incubated cells) of both
      free 3H-AA and 3H-PAF into the apical compartment but not into the basolateral
      compartment. Treatment of the BEAS cells with the phospholipase A2 (PLA2)
      inhibitor mepacrine (1 mM) prior to, and during, incubation with melittin
      inhibited the increase in 3H-AA and 3H-PAF release into the apical compartment by
      65% and 100%, respectively. Exposure of BEAS cells to ozone (O3; 1.0 ppm for 15
      min) increased the release of polar 3H-AA products as well as 3H-PAF into both
      the apical and basolateral compartments. Mepacrine did not significantly inhibit
      the O3-induced release of polar 3H-AA products or 3H-PAF into either the apical
      or basolateral compartments. These data suggest the direction of the release of
      3H-AA (or 3H-AA products) and 3H-PAF is stimulus-specific and that PLA2
      involvement in the release of the lipids is also dependent on the stimulus. The
      directional release of AA, AA products, and PAF may be important in the airways
      responses to various agonists and oxidants.

PMID- 7809386
TI  - Epidemiology of arboviral infections.
AB  - OBJECTIVE: To review the current state of knowledge regarding the epidemiology of
      arboviruses. DATA SOURCES: Computerized literature searches, identification of
      papers through review of article bibliographies, and Yale Arbovirus Research
      Unit, USA. STUDY SELECTION: Articles documenting research pertaining to the
      epidemiology of arboviruses with emphasis on factors that increase or decrease
      the spread of these infections. DATA EXTRACTION: The review articles were
      extracted independently by the authors. DATA SYNTHESIS: Arboviral infections are
      a global health problem accounting for significant morbidity and mortality in
      human and animal populations. They belong to the families Togaviridae,
      Flaviviridae, Bunyaviridae, Reoviridae, and Rhabdoviridae, and are transmitted to
      humans and domestic animals by the bite of infected arthropods. Rodents and birds
      are significant vertebrate hosts, while humans are usually not involved in the
      maintenance and spread of most arboviruses. Ecologic changes and human behavior
      are important in the spread of these infections. Clinical features range from
      mild fevers to fatal encephalitis. Surveillance, immunization, and vector control
      are important methods of prevention. CONCLUSION: It appears that the distribution
      and spread of arboviruses is greatly influenced by human behavior and ecologic
      changes in the environment. Awareness regarding these and other factors, such as
      travel history, history of bites of arthropods, concurrent epidemic pattern in
      the community, and knowledge of surveillance data are useful ways of identifying
      these infections. Future research may be directed toward methodical search for
      new arboviruses and their relation to human and animal disease.

PMID- 7809387
TI  - Do infant and early childhood tests predict intelligence quotients better than
      maternal characteristics?
AB  - The sensitivity, specificity, and predictive values of infant and early childhood
      testing for subsequent intelligence tests at 3 and 5 years of age were assessed
      and compared to the sensitivity, specificity, and predictive value of maternal
      education for the same. The study was based on prospective surveillance of a
      population of infants attending the Maternal and Child services in western
      Jerusalem. The sensitivity, specificity, and predictive value of the 9- and 24
      month tests were low, thus leading to labeling of false positives and inadequate
      detection of those with developmental delay. Maternal education was shown to be
      the single best predictor for intellectual performance on the 3- and 5-year test
      in the above analysis, as well as in a multivariate model where the 9- and 24
      month tests, maternal education, origin, birth order, and sex were introduced as
      independent variables. It is recommended to take a detailed history, listen to
      parents' complaints, and use developmental testing selectively for children
      suspected to have problems, and not to apply developmental tests as a routine for
      all children in well-child care.

PMID- 7809388
TI  - Past and present contraceptive behavior of new Soviet immigrant women in Israel.
AB  - This exploratory research investigated past and current use of contraceptives
      among a purposive sample of 117 new immigrant women from the Commonwealth of
      Independent States (former Soviet Union). The findings confirm the widespread use
      of induced abortion (IA) as a method of birth control before immigration. Fifty
      eight percent of the sample had had at least one IA, and the average was 2.7 IA.
      The most commonly used types of contraception before immigration were the pill,
      safe days, withdrawal, and the IUD. Currently used types of contraception were
      the IUD, safe days, withdrawal, and condoms; however only 45% of the sample were
      currently using any type of contraception. Of particular interest were the
      relatively high reported use of the pill before immigration and low current use,
      and the former low level of condom use and its increase in popularity in Israel.
      Despite the availability of more effective methods of birth control, safe days
      and withdrawal remain commonly used. The high cost of the pill was mentioned as a
      deterrent to its current use. Despite the high prior level of IA, the majority of
      women in this sample (84%) preferred today to use other birth control methods,
      and would like the opportunity to receive professional advice. These findings
      support the need for educational efforts directed toward new immigrant women from
      CIS.

PMID- 7809389
TI  - A mobile intensive care ambulance--use by community primary care teams.
AB  - OBJECTIVE: This study investigates the use of a mobile intensive care ambulance
      (MICA) by primary care teams in a large, semi-rural health district in northern
      Israel. METHOD: We reviewed the MICA records covering three years for all calls
      from a doctor or a nurse working in a community primary care clinic. RESULTS:
      Over the period studied, there were 649 such calls. Two-thirds of the patients
      were male, 70.5% were aged 60+ and only 2% were children under the age of one
      year. Of the total, 358 (55.2%) calls originated from kibbutzim (communal
      settlements), although only 7.5% of the district's population lives on such
      settlements. There were 12 calls (1.9%) from Arab villages, where 27.5% of the
      district population resides. The MICA personnel were more intervention prone than
      was the primary care team. The service was utilized mainly for cardiovascular
      emergencies and, in this study, children and residents of Arab villages appear to
      have been underserved. There was a disproportionately high representation of
      elderly kibbutz members. CONCLUSIONS: There is a need for further research to
      assess standards for emergency equipment in primary care clinics, and continuous
      training of the primary care team. Introduction of a high service technology such
      as the MICA might be a problem in certain populations.

PMID- 7809390
TI  - Cardiovascular risk factors by ethnic group and menstrual status among 13- and 14
      year-old Israeli schoolchildren.
AB  - BACKGROUND: Ethnic differences in cardiovascular risk factors have been
      demonstrated previously among Israeli children and adolescents. This study
      examines the prevalence of selected risk factors and risk factor clusters among
      13- and 14-year old Israeli schoolchildren according to ethnic origin and other
      demographic variables, and takes into account the unique contribution of
      menstrual status of the girls to risk factor differences. METHODS: Demographic
      and menstrual status (for the girls) data were obtained for 299 West Jerusalem
      eighth grade students. Height, weight, and blood pressure were measured, and
      blood was obtained for total cholesterol, high density cholesterol (HDL), and
      triglyceride measurements. Differences in mean Body Mass Index (BMI), blood
      pressure, and lipids, as well as in the percentage of children with specific risk
      factors or total number of risk factors were tested for among the various
      demographic and menstrual status groups. RESULTS: BMI was statistically
      significantly greater among females (20.2 kg/m2) than among males (19.46 kg/m2),
      (p = .04) and among menstruating females (21.1 kg/m2) compared with non
      menstruating females (17.9 kg/m2), (p = .000). Mean systolic blood pressure was
      higher among menstruating (109.8 mmHg) than non-menstruating (105.9 mmHg) females
      (p = .09). Statistically nonsignificant differences in mean systolic blood
      pressure and total cholesterol were found according to paternal country of
      origin. According to defined cutoff points, 8.7% of the students had elevated
      BMI, 2.8% had elevated systolic or diastolic blood pressure, and 13.0% had
      elevated total cholesterol. 17.5% of the students had one cardiovascular risk
      factor and 3.1% had two risk factors. CONCLUSIONS: The data demonstrate a high
      prevalence of cardiovascular risk factors without statistically significant
      ethnic differences in this population. Menstrual status exerted a unique effect
      upon BMI and systolic blood pressure. Pubertal status should be considered in the
      assessment of risk factors in early adolescents. Total-community-oriented
      intervention is recommended for this population.

PMID- 7809391
TI  - Israel Society for Microbiology, annual meeting. Rehovot, Israel, 14-15 February
      1994.

PMID- 7809392
TI  - [Fictional film and the audience. A metapsychological study].
AB  - Comparing and contrasting dreams and films we find a complex behind of affinities
      and distinctions between the dream state and the film state. The author
      classifies the totality of these partial distinctions and similarities in terms
      of three factors deriving from the discrepancy between sleep and the waking
      state: first, the inconsistent knowledge of the subject with regard to what he is
      doing; second, the presence or absence of real perceptual material; and third,
      the qualitative difference between dream text and film text. Metz shows that,
      unlike dreams, which obey primary events, films have much greater affinities with
      secondary events and the pre-conscious figments of daydreaming. Dreams, the
      author contends, belong to childhood and night, while films and daydreams are
      more adult and belong to the day and the evening.

PMID- 7809393
TI  - [The dis-positive: metapsychological observations of the reality impression].
AB  - In the author's view, Plato's myth of the cave is an exact description of the
      movie theatre. In both there is a constraint to immobility, repetition and a
      return to a former state--a primary-process throwback to the immobility of the
      newborn infant and the sleeper. The captive in the cave, the cinema-goer and the
      sleeper are all-albeit in different ways--victims of an illusion of reality, an
      impression that deviates from reality, and are hence subjects of the unconscious.
      It is this more-than-the-real, this desire for desire, that in Baudry's view
      informs the history of cinema.

PMID- 7809394
TI  - [Birth of the movie from the spirit of laughter].
AB  - So far, the links between film theory and psychoanalysis have been largely forged
      via Sigmund Freud's theory of dreams and the "linguistic turn" ushered in by
      Jacques Lacan. The present author elects a different approach. Drawing upon
      Freud's treatise on jokes, she outlines the way in which the social nature of
      joke production (in contrast to the loneliness of the dreamer) and the modes of
      wish-fulfillment inherent therein (neglected by Lacan) can be utilised for a
      feminist re-vision of cinema. According to Schlupmann, the unconscious factors
      inherent in jokes and comedy re-emerge in a radicalized form in three elements of
      cinema: in the technicality of film, the participation of women and the
      projective space represented by the movie theatre.

PMID- 7809395
TI  - ["A male view?" Texts on feminism film theory].
AB  - The author traces the course taken by psychoanalytically oriented feminist film
      theory from its beginnings in the late seventies. She situates its origins in the
      Anglo-American debate about the exclusion of female subjectivity from the cinema
      and the new awareness of the problem of the cinematic mise-en-scene of the gaze,
      of "visual pleasure". First, massive criticism was levelled at the exclusively
      male/patriarchal gaze of the viewer, then emphasis centred around the
      specifically female gaze as a category in aesthetic theory. Ultimately,
      psychoanalytic feminist film theory has turned its attention to films for women,
      melodrams and early movies in an attempt to capture the respective historical
      forms of female subjectivity that they reflect.

PMID- 7809396
TI  - [Images of the unconscious. On the history of psychoanalytic film theory].
AB  - In contrast to the customary practice of classifying everything that proceeds on
      theoretical lines vaguely connected with psychoanalysis as representing a
      contribution to "psychoanalytic film theory", the author reserves this term
      exclusively for work proceeding from Freud's version of psychoanalysis and done
      by actual psychoanalysts. Zeul traces the history of psychoanalytic film theory
      from its beginnings to the present, and shows that the majority of authors
      addressing the subject of psychoanalysis and cinema interpret films largely in
      terms of their content or "storyline", drawing upon categories of wish-fulfilment
      and narcissism to do so. In contrast to this, the author insists that the
      symbolic richness of a film can only be truly appreciated if its formal and
      aesthetic structure is taken seriously and the moving images are acknowledged as
      functioning in their own right. This contrast between content-oriented and formal
      film interpretation is to some extent reminiscent of the so-called "realism
      debate" in the thirties and forties, its protagonists being Georg Lukacs and
      Bertolt Brecht.

PMID- 7809397
TI  - Effects of age on the ability to remember common and rare proper names.
AB  - Difficulties in remembering proper nouns increase with age. One factor is that
      names are arbitrary labels. Another is that because many people share the same
      names, mutual discriminability between names is less than than that between other
      words. Discriminability between names may reduce as the number of acquaintances
      increases. Also, most people have both a first and a second name. These have to
      be learned as a pair, but they may be of unequal distinctiveness and so be
      unequally well remembered. An experiment was designed to evaluate the relative
      effects of distinctiveness of first and second names on free and cued recall.
      Subjects (aged 60-69 or 70-79 years, matched on Mill-Hill vocabulary score) were
      asked to remember one of four lists of 16 names. Each was presented four times.
      The names were either common, rare, or a combination of the two--a common first
      name with a rare surname, or vice versa. Subjects first freely recalled the
      names. They were next cued by either first name or surname to recall the
      remaining half of name pairs. Interactions between effects on recall of subjects'
      ages and of the relative distinctiveness of first and second names provide
      partial support for a model incorporating "relative distinctiveness" as a factor
      in failures of name recall in old age.

PMID- 7809398
TI  - Articulatory length and phonological similarity in span tasks: a reply to
      Baddeley and Andrade.
AB  - We report a partial replication of previous results by Caplan, Rochon, and Waters
      (1992), using methods that address objections raised by Baddeley and Andrade
      (this issue) and that improve on several techniques used by them. The results
      cast doubts on the role of articulation in determining the word length effect in
      span, and hence on the role of articulation in rehearsal.

PMID- 7809399
TI  - Attentional bias to threat: roles of trait anxiety, stressful events, and
      awareness.
AB  - Attentional biases for threat stimuli were assessed in high and low trait anxious
      subjects (n = 66) using a probe detection task. To examine the effects of trait
      anxiety and situational stressors, each subject was tested three times: Under no
      stress, laboratory-induced stress, and examination-induced stress. To evaluate
      the role of awareness, half the word stimuli were presented very briefly (14
      msec) and masked, and the other half were presented for 500 msec without a mask.
      Results showed that high trait anxious subjects under exam stress showed an
      attentional bias towards unmasked threat stimuli compared with low trait
      subjects. This effect was not found under lab-induced stress, suggesting that the
      attentional bias for unmasked threat in high trait subjects may be a function of
      a prolonged stressor, rather than a transient increase in state anxiety. The
      results from the masked exposure condition were not predicted; high trait anxious
      subjects shifted attention towards the spatial location of threat words despite
      lack of awareness of their lexical content, but this bias was only apparent in
      the no-stress condition. The results are discussed in relation to recent
      cognitive theories of anxiety.

PMID- 7809400
TI  - Attention reduces perceived brightness contrast.
AB  - The effects of attention on brightness perception was investigated in four
      experiments. In the first three, subjects estimated the brightness of a briefly
      presented small grey square by selecting a number that corresponded to one of
      four possible squares varying on a lightness-darkness dimension. In the last
      experiment, subjects matched the brightness of two peripheral squares, one
      attended and one unattended. When the stimulus appeared on a white background
      (Experiments 1, 2, and 4a) it was judged as brighter when attention was directed
      to its location than when attention was diverted to another location. When the
      stimulus appeared on a dark background (Experiments 3 and 4b), the opposite
      pattern of results was obtained: the attended stimulus was judged as darker than
      the unattended one. These results show that attention reduces the perceived
      contrast between the stimulus and its background, suggesting that attention
      enables subjects to provide a more veridical judgement of stimulus brightness by
      limiting processing resources to the square itself, at the expense of the
      surrounding background. As attention produced a directional brightness effect
      rather than just an improvement in report accuracy, the results can be attributed
      to early perceptual processing effects, hence providing support for early
      selection views of attention.

PMID- 7809401
TI  - Word recognition in developmental dyslexia: a connectionist interpretation.
AB  - We present a study of the accuracy, consistency, and speed of word naming in a
      dyslexic boy, JM, who has severe impairments in the ability to use sub-lexical,
      phonological reading strategies. For words that he can recognise, JM's naming
      latencies do not differ from those of control subjects matched for reading age,
      and he is generally consistent from one occasion to the next. He can also match
      printed homophones with their definitions--a skill that requires access to well
      specified orthographic representations. The data are interpreted as evidence for
      the creation of efficient recognition devices for words within JM's sight
      vocabulary. However, he shows a continuing inability to use phonological decoding
      strategies to deal with words that he cannot recognize by sight. Overall we argue
      our results pose problems for stage models of reading development, and that they
      may best be interpreted within a connectionist framework of the development of
      word recognition skills.

PMID- 7809402
TI  - A primacy effect in monkeys when list position is relevant.
AB  - In Experiment 1 (1a and 1b), Rhesus monkeys (Macaca mulatta) learned lists of two
      choice visual discriminations in which list position was relevant to
      discrimination performance. For example, Stimulus A was the rewarded stimulus if
      it was presented at List Position 1, but was not rewarded if it was presented at
      any other position in the list; similarly, Stimulus B was rewarded only at List
      Position 2, and so on. In learning these lists, all animals showed a marked
      primacy effect. In Experiment 2 (2a and 2b), Rhesus monkeys and Cynomolgus
      monkeys (M. fascicularis) learned lists of visual discriminations in which each
      visual stimulus occupied a fixed position in a list, but list position was not
      relevant to discrimination performance. For example, Stimulus E was always
      rewarded, and was always presented at List Position 1. To increase the salience
      of list beginning as a distinctive event, successive presentations of the list
      were separated by 24-hr intervals. In Experiment 2 there was no primacy effect,
      however. These results show for the first time that a primacy effect can be
      obtained in visual discrimination learning by monkeys. Furthermore, they suggest
      that it is obtained only when list position is relevant to the discrimination
      learning task.

PMID- 7809403
TI  - Discrimination of artificial polymorphous categories by rhesus monkeys (Macaca
      mulatta).
AB  - Monkeys (Macaca mulatta) were trained to discriminate between sets of artificial
      stimuli such as those used by Jitsumori (1993) for pigeons and humans. The
      stimuli were arrays of symbols differing along three two-valued (positive or
      negative) dimensions. The discrimination required was between polymorphous
      categories in which a positive stimulus was defined by possession of any 2 out of
      3 positive features. Of the 5 monkeys, 3 learned the discrimination much faster
      than did pigeons, but transfer to novel stimuli was less impressive than had been
      shown in pigeons. The 3 monkeys showed high levels of transfer to the stimuli
      that contained either all 3 positive or all 3 negative features, but 2 of the 3
      monkeys failed to show transfer to stimuli that had 1 of the 3 features replaced
      with a novel one. Analysis of the monkeys' performance raised doubts on the
      additive integration of features but supported learning of feature combinations
      as a basis for the discrimination of polymorphous categories by this species.

PMID- 7809404
TI  - Latent inhibition, context specificity, and context familiarity.
AB  - In two appetitive licking experiments, thirsty rats were pre-exposed on two
      stimuli prior to conditioning sessions in which one or both of these stimuli were
      paired with water. Consistent with other results, latent inhibition was disrupted
      when conditioning took place in a context different from that in which stimulus
      pre-exposure had occurred. But in animals given prior exposure to the context of
      stimulus pre-exposure before the start of stimulus pre-exposure, substantial and
      equivalent latent inhibition was evident whether or not there was a change of
      context between stimulus pre-exposure and conditioning. These results are
      discussed in terms of current theories of latent inhibition.

PMID- 7809405
TI  - Golden hamsters on the eight-arm maze in light and darkness: the role of dead
      reckoning.
AB  - This paper examines whether golden hamsters can rely on dead reckoning (getting
      positional information from updated signals generated during locomotion) on an
      eight-arm maze. Two groups of hamsters were tested: Group L under ordinary room
      light, Group D in darkness. To enhance the role of dead reckoning, each subject
      could climb from its own home cage onto the central platform of the maze. In a
      first experimental phase (15 trials), the L subjects learned to master the maze
      through developing a locomotor rule (arm chaining) after three to four trials.
      The D subjects developed arm chaining less readily and fluctuated more in their
      performance than did the L subjects. In a second experimental phase (15 trials),
      four arms were blocked at the beginning of each trial. In both experimental
      groups the performance decreased, yet remained well above chance level. Success
      and arm chaining were positively correlated in Phase 1 and negatively correlated
      with success in Phase 2. We assume that in Phase 2 the L subjects switched to the
      predominant use of visual cues, and the D subjects to dead reckoning.

PMID- 7809406
TI  - Effects of the interval between exposure to a novel environment and the
      occurrence of shock on the freezing responses of rats.
AB  - Rats were exposed to a novel environment (E1) at time T1, given a footshock at
      time T2, and tested for freezing in E1 or in a second environment (E2). The
      function relating freezing to the T1-T2 interval among rats tested in E1 was an
      inverted U-shape. Rats exposed to short T1-T2 intervals displayed just as much
      freezing in E2 as in E1, whereas rats exposed to longer intervals froze less in
      E2 than in E1. These differences between the freezing responses in E1 and in E2
      were obtained when the T1-T2 intervals were varied, but time spent in the shocked
      E1 was equated. Rats given two shocks in E1 differentiated between E1 and E2 when
      the initial shock occurred some time after exposure to E1, but not when the
      initial shock was presented shortly after that exposure. Rats shocked some time
      after exposure to E1 on Day 1 and shortly after exposure to that environment on
      Day 2 differentiated between E1 and E2 more than did rats exposed to the reverse
      sequence of T1-T2 intervals. The results were attributed to the formation of a
      network of connections among the E1 cues in rats exposed to moderate or long T1
      T2 intervals, and to an impairment in the formation of this network as a result
      of the conditioning of a subset of cues in rats exposed to short T1-T2 intervals.

PMID- 7809408
TI  - Analysis of knee movement with low-field MR equipment--a normal volunteer study.
AB  - This study was performed to make a normal standard by analyzing normal knee
      movement in detail. An open low-field unit was used for 23 healthy knee joints.
      With three-dimensional Fourier transformation (3DFT) gradient echo sequence, 50
      sagittal slices of 4.5 mm in thickness were obtained at four flexion angles: 0,
      30, 60, and 90 degrees (lateral position). Although the tension ratio of the
      anterior and posterior cruciate ligaments (ACL, PCL) increased during knee
      flexion, the change in the tension ratio was significantly different between the
      ACL and PCL. The femur-ACL angle and femur-PCL angle were parallel with the knee
      flexion angle, but the tibia-ACL angle and tibia PCL angle changed complexly. The
      lateral and medial condyles rolled and slid during knee flexion, and the medial
      side moved more than the lateral side, consistent with rotation of the lower
      thigh. The difference in backward movement distance on the tibia between the two
      condyles was significantly larger in females than in males. This might explain
      the dominance of knee osteoarthritis in women. Although the lateral position is
      not completely physiological, we could show initial cinematic data of up to 90
      degrees of knee flexion using open-type MRI, which is impossible with high- and
      middle-field machines.

PMID- 7809407
TI  - Contrast-enhanced gradient-echo MR imaging of the head and neck: experimental and
      clinical assessment.
AB  - To clarify the enhancement pattern of gradient-echo (GE) MR imaging, phantom
      experiments and 24 clinical examinations of the head and neck region were
      performed. Both long repetition time (TR) GE and short TR GE pulse sequences
      demonstrated an enhancement pattern similar to T1-weighted spin-echo imaging in
      phantom experiments, although the signal intensity of water and gadopentetate
      dimeglumine (Gd) solution was higher and the signal intensity of fat was lower
      with the GE technique. In clinical examinations, contrast-enhanced GE imaging was
      beneficial for tumors within fatty tissue, and for tumors with calcification or
      other magnetic susceptibility difference.

PMID- 7809409
TI  - 3D-CT angiography of cerebral aneurysms with spiral scanning: comparison with 3D
      time-of-flight MR angiography.
AB  - To compare the clinical value of three-dimensional (3D)-CT angiography using
      spiral scanning and 3D-time-of-flight (TOF) MR angiography in the diagnosis of
      cerebral aneurysms, the results of these studies were compared in 12 patients
      with a total of 17 aneurysms. In seven of the 17 aneurysms, anatomic details were
      visualized better by 3D-CT angiography than by MR angiography. Both studies
      demonstrated five aneurysms equally well. MR angiography delineated three
      aneurysms better than 3D-CT angiography. Both studies failed to demonstrate two
      very small aneurysms. In 3D-CT angiography, aneurysms were viewed from many view
      angles, allowing the assessment of the spatial relationship between an aneurysm
      and the surrounding vascular and bone structures. Considering the use of contrast
      material and irradiation, 3D-CT angiography is of value in delineating aneurysms
      which are equivocal on MR angiography. In addition, 3D-CT angiography is a
      potential preoperative adjunct to conventional angiography.

PMID- 7809410
TI  - Iodine-131 treatment of thyroid cancer: relation between effective half-life and
      efficacy of treatment.
AB  - The effective half-life (Teff) of radioactivity taken up by residual thyroid
      tumor after 131I therapy was measured and compared with response to treatment.
      Teff was determined from uptake by the lesions at four, eleven, and 18 days after
      131I administration. The criterion for successful 131I therapy was that, in any
      successive 131I therapy, lesion uptake in the second therapy decreased to less
      than one-twentieth of that in the first therapy. In the 26 patients studied, 48
      lesions were evaluated. Therapy was considered successful in 27 of these lesions
      and unsuccessful in 21. Mean Teff in the former was 2.48 +/- 0.93 days (mean +/-
      S.D.), significantly shorter than that in the latter, 5.70 +/- 2.62 days (p <
      0.001). In some of the cases of solitary lesion, serum TSH levels, serum
      thyroglobulin values, and 131I protein bounded iodine (131I-PBI) were measured,
      but there were no significant differences between successful and unsuccessful
      therapy. The results of this study suggest that Teff seems to reflect the
      functional nature of the lesion and could be of prognostic value for the response
      to 131I therapy.

PMID- 7809411
TI  - Gastric syphilis: case report and review of the literature.
AB  - A 35-year-old Japanese woman consulted our clinic with a one-month history of
      epigastric pain. Although a superficial depressed type of early gastric carcinoma
      was highly suspected from the results of upper gastrointestinal barium studies
      and gastroscopy, there was no evidence of malignancy in the biopsy specimen.
      Gastric syphilis was then considered based on skin lesions and serological
      studies. Diagnostic antisyphilitic therapy improved the symptoms and gastric
      lesion promptly. A review of the recent reports indicated that most cases of
      early phase gastric syphilis seem to present morphologically either as a
      narrowing lesion or shallow ulcero-nodular lesion at the pyloric antrum.
      Therefore, whenever such findings are recognized either radiologically or
      gastroscopically and no malignant cells are found in biopsy specimens, gastric
      syphilis and diagnostic antisyphilitic therapy should be considered.

PMID- 7809412
TI  - Unusual manifestations of rectal duplication cyst: a case report.
AB  - An unusual rectal noncommunicating duplication cyst in an adult is described. The
      cyst was filled with a homogeneous high-density substance on computed tomography,
      which was also visible on plain radiography. We were unable to find any previous
      similar report in the literature.

PMID- 7809413
TI  - Assessment of congenital left ventricular diverticulum by magnetic resonance
      imaging: comparison with myocardial perfusion.
AB  - We report two cases of left ventricular diverticulum assessed by magnetic
      resonance (MR) and radionuclide imaging. MR imaging clearly demonstrated the
      diverticulum in each case, where abnormal perfusion was observed on Tl-201
      myocardial SPECT.

PMID- 7809414
TI  - Hepatic adenoma: report of three cases and review of the literature.
AB  - Pathologically confirmed hepatic adenoma (HA) was observed in two women who were
      not using contraceptives and one 60-year-old man. All three cases had a mass in
      the right lobe of the liver and almost normal laboratory results. One case that
      had a movable pedunculated mass mimicked an extrahepatic tumor preoperatively,
      and two cases associated with acute abdominal pain resulting from intratumor
      hemorrhage were misdiagnosed as hepatoma and given interventional therapy prior
      to liver biopsy. In hepatic arterial DSA of two cases, the tumor appeared as
      hypervascular with peripheral blood supply and regularly parallel branches
      coursing centrally. On CT scans, the tumor appeared to be surrounded by a low
      density ring in two cases, and an intratumor hyperdense area of fresh blood was
      noted in one case. Analysis of the three cases in this series and a review of the
      literature indicated that if the DSA and CT findings described above were
      revealed in a patient, particularly a young woman, with a mass of the right lobe
      of the liver (with or without acute abdominal pain) and normal laboratory
      results, HA should be strongly suspected, and CT-guided biopsy should be
      performed for pathological diagnosis, particularly when an equivocal diagnosis is
      made.

PMID- 7809415
TI  - Assessment of the cerebrovascular response to acetazolamide using 99mTc-DTPA-HSA:
      methodological considerations.
AB  - We have reported methods of assessing the cerebrovascular response to
      acetazolamide using 99mTc-DTPA-HSA and their usefulness in evaluating cerebral
      hemodynamics. Several problems of this technique were investigated in 10 normal
      subjects. Following 99mTc-DTPA-HSA injection, dynamic imaging of the anterior
      head view was performed for 25 to 50 minutes, and 10 minutes after the beginning
      of imaging, 1,000 mg of acetazolamide was infused intravenously. Venous blood
      samples were obtained during the imaging period to estimate the blood retention
      of 99mTc-DTPA-HSA. Radioactivity in the head increased for about 10 minutes
      following acetazolamide infusion, then decreased slowly. The declining phase
      almost disappeared after correction for the blood clearance of 99mTc-DTPA-HSA,
      indicating stability of the vasodilatory effect of acetazolamide. Dilatation
      index, the percent increase in activity, was a little smaller after correction,
      but was closely correlated with the index without correction. There was a high
      correlation between dilatation indices obtained by two analyses, including ROI
      setting and visual determination of the peak, of the same data. In conclusion,
      neither blood clearance of 99mTc-DTPA-HSA nor subjective analysis considerably
      impairs the reliability of the dilatation index, and blood volume in the head
      from about 15 to 40 minutes after acetazolamide injection is stable and suitable
      for SPECT.

PMID- 7809416
TI  - Rectangular field of view for dynamic MR imaging of sellar and parasellar
      regions.
AB  - The effectiveness and quality of a rectangular field of view (R-FOV) were
      compared with those of a square FOV (S-FOV) in dynamic MR study of sellar
      regions. Cranial nerves in the cavernous sinus were identified more clearly with
      R-FOV. The image quality grading of R-FOV was significantly superior to that of S
      FOV.

PMID- 7809417
TI  - Toxicology of monocrotophos.
AB  - Monocrotophos is a water-soluble organophosphate insecticide with high oral and
      moderate dermal toxicity. The toxicologically relevant mode of action is the
      inhibition of ChE activities. The toxicity of organophosphate metabolites of
      monocrotophos is comparable with the parent compound. Glycol conjugation in plant
      metabolism decreased the acute toxicity significantly. Dephosphorylated
      metabolites showed no demonstrable acute toxicity. Repeated exposure to the
      compound leads to initial cumulation of the single-dose effects. At moderate dose
      levels, the adverse effects are counteracted by an increase of tolerance through
      adaptation. A study in humans demonstrated no relevant ChE depression over a 30-d
      period at daily dose levels of up to 0.006 mg/kg. Lifetime chronic feeding
      studies in rodents again indicated ChE inhibition as the only specific effect.
      Body weight reduction was limited to high doses. No gross or microscopic specific
      lesions were demonstrable; especially, there was no evidence of oncogenic
      effects. Genotoxicity was evident in vitro, whereas comprehensive assessment of
      the in vivo tests indicates no toxicologically relevant mutagenic potential in
      mammals. This conclusion is supported by the absence of oncogenic effects in
      chronic feeding trials. Findings in reproduction studies were limited to
      secondary fetal reactions that were triggered by maternal toxicity. Acute and
      repeated administration studies in hens revealed no delayed (degenerative)
      neurotoxic potential. Monocrotophos showed no significant potentiation with 24
      other ChE inhibitors. Poisoning signs after heavy doses were controlled by
      therapeutic doses of atropine, preferably in combination with an oxime.

PMID- 7809418
TI  - Residue analytical methods for monocrotophos.
AB  - This paper summarizes and reviews a variety of methods that have been and are
      being used for the determination of residues of monocrotophos. Of the different
      techniques, gas-liquid chromatography was recommended as the technique of choice
      because it is sensitive as well as selective. The other techniques reviewed may
      still be useful in cases where gas chromatography is not available. The
      recommended methods were described in detail to allow their direct use by
      experienced residue analysts. Some multiresidue methods that include
      monocrotophos and may be used for surveillance purposes were briefly discussed.

PMID- 7809419
TI  - Formulation of monocrotophos.
AB  - Monocrotophos is an old product that is still very much appreciated as a low-cost
      and efficient insecticide. Due to its water solubility, formulation recipes are
      rather simple and no sophisticated equipment is required in a formulation plant.
      Formulations can easily be manufactured locally where they are going to be used.
      Formulants and the formulation process do not add much to the total product cost.
      Monocrotophos is chemically not very stable. A consequence of this property is
      the marginal shelf life of formulations when stored under tropical conditions. On
      the other hand, the limited stability of monocrotophos is a most favorable
      feature in the environment that outweighs the marginal shelf life. By strictly
      using the "first in-first out" system in stock management, no major problems
      relating to storage stability will be encountered. An unfavorable characteristic
      of monocrotophos is its high mammalian toxicity. The objective of future projects
      will be to develop less toxic formulations.

PMID- 7809420
TI  - Monocrotophos--worker safety.
AB  - Monitoring data on field-worker exposure studies show that prolonged or continued
      use of monocrotophos in plant protection may lead to significant dermal exposure
      with an impact on cholinesterase activity. Although oral uptake (suicide) is more
      hazardous than dermal exposure (spray work), both exposure routes may be
      potentially fatal. On the other hand, prompt therapy is successful even after a
      heavy oral dose. The epidemiological review did not reveal a prominent risk
      scenario. Justification of monocrotophos use depends on agricultural need and
      appropriate safety measures. Eighteen cases of monocrotophos poisoning have been
      identified in the literature and from the manufacturer's case file. Seven cases
      were occupational, and nine resulted from suicide attempts. One case was a
      nonprofessional accident, and one was recorded without details. Further
      monocrotophos poisoning cases may be concealed in the unspecified data on
      poisoning among tropical farming communities. However, the fact remains, that
      only a small number of reliably reported poisoning cases are attributable to
      monocrotophos products, and the reports confirm the efficacy of basic medical
      attention to poisoning. This is in contrast to the high hazard classification and
      to the high perceived hazard of the products in question. Safetywise,
      monocrotophos appears to be better than its reputation. A level of safety
      precautions normally recommended for pesticide work is sufficient, even under
      large-scale professional use conditions, to utilize monocrotophos safely.

PMID- 7809421
TI  - Metabolism of monocrotophos in animals.
AB  - Regarding the metabolic fate of monocrotophos, it appears that the mechanisms
      summarized below are largely independent of the animal species. Furthermore,
      significant sex dependency of any of these parameters has not been found.
      ABSORPTION: After oral administration to rats and goats, monocrotophos is rapidly
      and almost completely absorbed from the intestinal tract. There is convincing
      evidence that monocrotophos is readily absorbed after dermal administration to
      man, pigs, and rabbits. DISTRIBUTION: Monocrotophos and/or its metabolites are
      evenly distributed between the tissues and organs of the animals; usually, the
      highest concentrations are typically found in organs involved in the elimination
      process, i.e., liver and kidney. There are no indications for any organ-specific
      retention. In assessing the relevance of tissue residues, the fact that
      monocrotophos may contribute to the carbon pool and may thus, via de novo
      synthesis of endogenous compounds, lead to nonmonocrotophos-related 14C-residues
      needs to be considered. METABOLISM: The biotransformation of monocrotophos is
      well understood. Three different metabolic reactions are involved in the initial
      biotransformation: N-demethylation, O-demethylation, and cleavage of the vinyl
      phosphate bond. The compound is completely degradable, ultimately leading to CO2.
      All carbon atoms of the molecule have the potential to enter the carbon pool.
      EXCRETION: After absorption and biotransformation, monocrotophos and/or its
      metabolites are rapidly eliminated from the animals. Excretion is predominantly
      in the urine, typically 70-90% of the dose, and usually less than 10% is voided
      with the feces. Significant amounts, i.e., 6% of the crotonamide backbone, is
      expired as CO2 by rats. In lactating goats, approximately 2% of the dose is
      eliminated with the milk. Due to the water solubility of monocrotophos, some
      portion of the dose may escape biotransformation and consequently be excreted
      unchanged.

PMID- 7809422
TI  - National standards and guidelines for pesticides in water, sediment, and aquatic
      organisms: application to water-quality assessments.
AB  - National standards and guidelines for pesticides can be useful tools in water
      quality assessment for evaluating potential human health or ecological effects of
      measured pesticide residues in water, bed sediment, or aquatic organisms.
      However, valid use of a given standard or guideline requires an understanding of
      its technical basis and underlying assumptions. Each type of standard or
      guideline is specific for one sampling medium (water, bed sediment, and fish and
      shellfish tissue) and is aimed at protection of one or more beneficial uses of
      the hydrologic system (drinking water, fish and shellfish consumption, aquatic
      organisms, and wildlife). These characteristics can be used to identify which
      standards and guidelines are appropriate for comparison with measured pesticide
      concentrations in environmental samples from a given hydrologic system. A review
      of standards and guidelines can be restricted to the applicable sampling medium.
      Then, the beneficial uses of the hydrologic system need to be identified and the
      measured pesticide concentrations compared with standards and guidelines for all
      beneficial uses that apply to that system. Several key factors that must be
      considered when applying this general process to water-quality assessment are
      summarized below. Two precautions need to be considered regarding sampling media:
      1. Standards and guidelines for water distinguish between finished drinking water
      (potable water, often treated) and ambient surface water. If standards and
      guidelines for drinking water (EPA primary drinking-water regulations and
      drinking-water health advisories) are applied to measured pesticide
      concentrations in ambient water samples, the effects of water treatment (such as
      filtration) need to be considered. 2. Standards and guidelines for fish and
      shellfish tissue distinguish between edible fish and shellfish tissue and whole
      fish tissue. Comparison of pesticide concentrations in whole fish tissue with
      standards or guidelines for edible fish and shellfish tissue is appropriate only
      as a screening procedure to determine whether additional sampling and analysis
      for contaminants in edible fish fillets are warranted. For some sampling media
      (water, fish and shellfish tissues), both standards and guidelines may exist for
      a given pesticide. Standards and guidelines may differ in their technical bases
      and in the implications or consequences of finding measured concentrations in
      exceedance of the standard or guideline value. Therefore, comparison of measured
      pesticide concentrations with both standards and guidelines is useful because
      each provides different information about the hydrologic system.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7809423
TI  - Cumulative and comprehensive subject matter index volumes 131-140.

PMID- 7809424
TI  - [Alberto Krug Penafiel].

PMID- 7809425
TI  - [Knowledge and beliefs of the effect of menopause and estrogenic therapy on
      health. Study in women attending the Barros Luco-Trudeau Hospital].
AB  - The benefits of hormonal replacement therapy are widely known. In spite of this,
      the proportion of women under treatment is low. The study aims to evaluate the
      amount of knowledge that patients have, about menopause, and how it influences
      compliance with therapy. In our study, 494 women attending the outpatient's
      clinic of Hospital Barros Luco-Trudeau were interviewed; 93.5% considered that
      menopause has adverse effects upon health; 87.9% believes that it produces
      emotional disturbances; 55.1% bone-related and 40.9% cardiac problems. Sixty six
      point eight percent of the consulted women know that there is a treatment for
      menopause. Half of the women interviewed had consulted the physician specifically
      for this reason; however, only one third are or were under treatment. Obesity,
      hirsutism and cancer are considered to be the main secondary effects to
      treatment. Patients who have not received hormone therapy have a much lower
      degree of knowledge about menopause than the treated ones, and amongst the
      latter, those who abandon treatment have less information than the ones that
      remain under treatment. As a conclusion, we may say that our patients have
      information about menopause and also that they attend to the physician's office
      for this reason. The knowledge about the matter and related beliefs influence
      both adherence to and compliance with therapy.

PMID- 7809426
TI  - [Evaluation of maternal and fetal blood flow indices in intrahepatic cholestasis
      of pregnancy].
AB  - To determine the existence of any change in the blood flow velocity indexes in
      patients with cholestasis of pregnancy, we studied a total of 51 pregnant women,
      (normal n = 15; anicteric cholestasis n = 21 and icteric cholestasis n = 15).
      There was no significant change in the parity, maternal age, gestational age,
      birth weight and in the apgar score among the groups. There was also no
      significant change in any of the blood flow indexes determined in the uterine
      artery, umbilical artery and fetal cerebral artery. We conclude that there are no
      significant changes in blood flow velocity indexes determined by doppler blood
      flow analysis in patients with cholestasis of pregnancy.

PMID- 7809427
TI  - [Behavior of flow waves of the uterine and external iliac arteries during labor
      contractions].
AB  - To evaluate the changes of blood flow velocities of the uterine and external
      iliac arteries, we studied a total of 15 normal full term pregnant, which were in
      the active phase of labor. The mean maternal age was 21.6 +/- 5.2 years (X +/-
      SD), the mean parity was 0.6 +/- 0.5, and the mean gestational age was 39.2 +/-
      1.1 weeks. All patients had normal deliveries, the newborn weight was 3440 +/-
      621 g, and the apgar score was 8.6 +/- 1.6 and 9.0 +/- 0.7 at 1 and 5 min,
      respectively. In the uterine artery, the systolic/diastolic ratio and the
      resistance index increased significantly from 1.83 +/- 0.25 to 4.24 +/- 1.55 (p <
      0.05) and from 0.46 +/- 0.05 to 0.74 +/- 0.08 (p < 0.01), respectively from the
      relaxation phase to the contraction phase. In all 15 patients the external iliac
      artery showed a reverse diastolic flow during uterine relaxation, whereas only 2
      of the 14 patients showed this reverse flow during uterine contraction (p <
      0.01). Furthermore, the flow velocity was modified with maternal
      hyperventilation. Finally, we conclude that uterine contraction induced profound
      changes in the blood flow velocities in the uterine and external iliac arteries.
      We proposed that these changes could be explained by uterine muscular
      contractions causing the blood flow to be shunted to areas of less resistance.

PMID- 7809428
TI  - [Postpartum tubal sterilization with the Parkland technique].
AB  - The purpose of this prospective study was to ascertain the simplicity, safety and
      effectiveness of the Parkland technique for puerperal tubal sterilization by
      minilaparotomy in 315 consecutive patients who underwent this procedure. Overall
      were healthy women sterilized for contraceptive reasons, for potential
      obstetrical high risk: great multiparity and/or reiterative cesarean section. The
      patients' mean age was 32.5 years (range, 23-39) and the mean parity 4.0 (range,
      3-7). In 6 cases (1.9%) light intraoperative mesosalpinx bleeding was easily
      controlled. No other complaints in connection with the procedure was noted. There
      was not cases of failed sterilization: 0.0% of pregnancy rate after the
      procedure, with a mean follow-up period of 36 months (range, 12-60). From this
      study it appears that the Parkland technique is a very simple, safe and effective
      procedure for postpartum sterilization.

PMID- 7809429
TI  - [Non-therapeutic cone: surgical or conservative management?].
AB  - Histological reports of 94 conization specimens with margins' involvement were
      reviewed. Macroscopically and histologically features of cones and subsequent
      hysterectomy specimens are described, (N = 70). Patients parity (4.1 vs 2.9
      births), cone's height (16.8 mm vs. 21.4 mm) and endo-or exocervical location of
      margins involvement were found to be statistically different between groups with
      and without residual disease at hysterectomy, (p < 0.01, p < 0.05 and p < 0.001).
      No predictable index was found at multiple variable analyses.

PMID- 7809430
TI  - [Genital microbial flora in a population of high obstetrical risk].
AB  - There is increasing evidence showing the association between maternal genital
      infection, prematurity and neonatal or maternal morbidity. To know the genital
      flora of women attending a high risk pregnancy service, 73 consecutive pregnant
      women attending the high risk pregnancy service at the Hospital San Borja
      Arriaran from may to august 1992 were included in this study, 75.3% of the
      vaginal discharges corresponded to fluids of normal appearance and 24.7% were
      altered. The microorganisms most frequently isolates were lactobacilli, U.
      urealitycum and coagulase negative strains of Staphylococcus. The Gram stain
      revealed the existence of bacterial vaginosis in 20.9% of the vaginal smears.
      There was a significant higher incidence of lactobacilli in patients with
      balanced healthy vaginal flora, whereas Gardnerella vaginalis and Mycoplasma
      hominis were isolated significantly more frequently from women with bacterial
      vaginosis. With the exception of genital mycoplasma, it was found a low incidence
      of sex transmitted bacteria in this study.

PMID- 7809431
TI  - [Uterine leiomyoma: pathology and epidemiology].
AB  - Two hundred biopsy reports with uterine myoma histopathological diagnosis were
      studied 67% of the cases were between 41-50 years of age. Premenopausic patients
      showed an average number of myomas almost three times higher than the
      postmenopausic women. The most frequent myoma were those within the walls with a
      size less than 2 cm. Chronic inespecific cervixitis was the most frequent finding
      in the cervix pathology, with in 1.5% of the cases. In 2 cases (1%) endometrial
      adenocarcinoma was found. In 60.5% of the cases one or both tubes and ovaries
      were removed neither case had malignant alterations. In 51 cases (25.2%) the
      myoma presented some type of degeneration, the most frequent being the cellular
      type, 16 out of 200, which represented 8% of the cases; it was considered as
      presarcomatose type. Presurgical clinical behavior is discussed considering the
      analysis of these figures and the perspectives of the conservative treatment with
      the use of new no ablative technique.

PMID- 7809432
TI  - [Induction of fetal lung maturity with combined hormonal therapy in premature
      labor].
AB  - Thyrotropin Releasing Hormone (THR) induce fetal pulmonary maturation by direct
      stimulation, and increase of fetal T3 and T4 which produce biochemical and
      structural pulmonary maturation. To evaluate the effectivity of TRH associated to
      corticoides in the prevention of respiratory distress syndrome (RDS) in premature
      labor, we administered TRH plus Cidoten to patients with imminent premature labor
      and gestational age (GA) < or = 32 weeks. In a total of 12 patients, tolerance
      was good in 85% (n = 10), birthweight was 1.782 +/- 488 g (x +/- 2 SD). RDS
      incidence of only 15.3% and chronic lung disease (CLD) incidence = 0. Newborn of
      mothers treated with TRH plus corticoids form in evident premature labor in our
      unit, showed laser rates of RDS and CLD than the described in literature for
      newborn of similar weight and GA treated only with corticoids.

PMID- 7809433
TI  - [Myomectomy to preserve fertility].
AB  - Myomectomies were performed an 38 patients and 69.9% of this patients become
      pregnant. The importance of this intervention is highlighted for the significance
      of pregnancy in older women.

PMID- 7809434
TI  - [Prevention of neutral tube closure defects, apropos of a case of iniencephaly].
AB  - We present a newborn with a malformation in the central nervous system that isn't
      frequent, the ininencephaly: this consist in the absence of the squamous part of
      the occipital bone, exaggerated cervical-thoracic retroflexion, high
      raquischisis, and with other malformations. Died at half hour, by global
      insufficiency respiratory due lug hypoplasia, verify by necropsies. In the Clinic
      Hospital of the University of Chile the incidence is 1 in 40,000 life newborn. We
      review the prevent of the nerval tube defect with the use of folic acid in the
      diet of the future woman who is going to became pregnant.

PMID- 7809435
TI  - Salmeterol in the management of paediatric asthma.

PMID- 7809436
TI  - Metered-dose inhalers and CFCs: what respiratory physicians need to know.

PMID- 7809437
TI  - Testosterone levels during systemic and inhaled corticosteroid therapy.
AB  - Testosterone has importance both as a sex hormone and as an anabolic steroid
      promoting bone formation. Osteoporosis is associated with both hypogonadism and
      corticosteroid therapy. Testosterone levels are reduced by long term prednisolone
      treatment. Although high dose inhaled corticosteroid therapy may cause a variety
      of systemic effects including adrenal suppression, dermal thinning and a
      reduction in total bone calcium, its effect on testosterone levels is not known.
      Testosterone, luteinizing hormone, follicle stimulating hormone and sex hormone
      binding globulin were therefore measured in 35 male patients with respiratory
      disease attending an outpatient clinic (median age 58, range 21-75 years). They
      were grouped according to steroid therapy and compared with 19 age matched
      controls. Mean (SD) testosterone levels were 33% lower in 12 men on long term
      oral prednisolone [14.5 (6.0) nmol 1-1] than in controls [21.7 (6.3) nmol 1-1],
      but were not significantly reduced in 10 patients on low dose inhaled
      beclomethasone [200-800 micrograms day-1: 19.7 (3.7)] nor in 13 men taking high
      dose inhaled beclomethasone [1500-2,250 micrograms day-1: 17.9 (5.6)]. Levels of
      luteinizing hormone, follicle stimulating hormone and sex hormone binding
      globulin were similar in all four groups. These cross sectional data confirm that
      long term systemic corticosteroid therapy reduces testosterone levels. However,
      testosterone was reduced by only 18% (NS) by long term inhaled corticosteroids.
      Other mechanisms to explain the disordered bone metabolism should now be
      explored.

PMID- 7809438
TI  - The effect of nebulized salbutamol therapy on the incidence of postoperative
      chest infection in high risk patients.
AB  - Patients who smoke heavily and those with pre-existing airflow obstruction are at
      particular risk of postoperative respiratory infection following upper abdominal
      surgery. This invariably prolongs hospital stay and increases morbidity. In order
      to determine whether high dose bronchodilator therapy in the perioperative period
      reduced the risk of infection, all patients undergoing elective upper abdominal
      surgery were assessed for risk of developing postoperative infection. Fifty-three
      patients were identified as high risk according to previously published criteria
      and were randomly allocated to receive nebulized salbutamol (5 mg) or saline
      placebo 6 hourly for 48 h beginning 1 h preoperatively. There was no difference
      in rates of postoperative chest infection in the two groups and this study,
      therefore, provides no support for the routine preoperative use of
      bronchodilators in these patients.

PMID- 7809439
TI  - Pulmonary tuberculosis in overseas students of higher education is increasing in
      Edinburgh.
AB  - In Edinburgh in 1991 a relative excess of pulmonary TB cases in the 15-34 year
      age group was recorded. Five of 17 notifications in this age group were of
      overseas students of higher education: three aged 21-29 from Central Africa, one
      27-year-old Asian and one 26-year-old Western European. One of the African
      students was seropositive for HIV infection. Disease presented clinically on
      average 31 months after entry to the U.K. (range 6-48 months). Four students had
      smear positive disease. Two patients had had normal chest radiographs 1 and 2
      years previously on entry to the U.K.; three students had not previously been
      radiologically screened. We suggest that students from countries with a high
      prevalence of tuberculosis should be screened on entry to their course of
      education and that student health services should develop and maintain a high
      index of suspicion for tuberculosis in these students.

PMID- 7809440
TI  - Cystic fibrosis in children from ethnic minorities in the West Midlands.
AB  - BACKGROUND: We have observed that Doctors often perceive that cystic fibrosis
      (CF) is exceptionally rare in non-whites, and that this bias has repeatedly
      resulted in diagnostic delay. We therefore compared the age at diagnosis, genetic
      features and relative prevalence of CF in non-whites and white patients in the
      West Midlands. METHODS: Analysis of data on all CF patients diagnosed in
      childhood and stored in the West Midlands CF register. RESULTS: Sixteen of the
      514 children on the register were not of white European extraction, comprising 13
      patients whose families originated from the Indian subcontinent, two of mixed
      AfroCaribbean/white European extraction and one of mixed Pakistani/white European
      extraction. The median age of diagnosis was similar in the white European and non
      white patients (0.42 vs. 0.33 years, 95% CI for the difference of the medians 
      0.15, 0.37). However, in five cases with typical clinical features the diagnosis
      appears to have been delayed because of the child's racial origin (median age of
      diagnosis 3.87 years), and in five others the diagnosis was obvious (two siblings
      with CF, three had meconium ileus). There was a degree of consanguinity in nine
      cases. Five patients were homozygous or heterozygous for the delta F508 mutation,
      but no mutation could be identified in the remaining 11 patients. CONCLUSIONS:
      The possibility of CF needs to be considered in any patient with relevant
      clinical problems, regardless of racial origin. These findings need to be
      considered when planning any mass population screening programme for CF.

PMID- 7809441
TI  - The Flutter VRP1 as an adjunct to chest physiotherapy in cystic fibrosis.
AB  - The Flutter VRP1 (Flutter) is claimed to increase the clearance of excess
      bronchial secretions and to improve lung function and oxygenation, but these
      claims were based on computer models, laboratory assisted experiments and
      uncontrolled clinical trials. A prospective randomized clinical trial was
      undertaken, in subjects with cystic fibrosis, using the active cycle of breathing
      techniques as the 'gold standard'. The claims could not be substantiated and the
      possibility of sputum retention was of concern when the Flutter was used as
      significantly more sputum (P < 0.001) was cleared with the active cycle of
      breathing techniques alone. There were no significant changes in lung function or
      oxygenation.

PMID- 7809442
TI  - Audit of procedures related to outcome of chest clinic consultation.
AB  - We audited the case records of 493 new patients referred to a chest clinic to
      determine for eight consultants and five middle-grade staff the average number of
      investigations performed, the follow-up rate and prolixity (the length of the
      letter written to the general practitioner). The outcome of the consultation was
      assessed by a questionnaire administered to the patients' general practitioners.
      Practitioner mean investigation rates varied from 0.1 to 8.7 investigations per
      patient, follow-up rate from 45 to 100% and average prolixity from 53 to 200mm.
      The prolixity of the eight consultants was significantly related to their
      investigation and follow-up rates. Consultation outcome was at least satisfactory
      for 97.4% of patients. We conclude that considerable potential exists for savings
      of laboratory, clinic and secretarial time and costs by reducing investigation
      and follow-up rates and writing shorter letters to general practitioners.

PMID- 7809443
TI  - A criterion based audit of community-acquired pneumonia.
AB  - We undertook a prospective audit of patients admitted to a specialist respiratory
      unit in order to assess: (a) the completeness of the objective assessment of
      severity of community-acquired pneumonia in patients on admission to hospital,
      and whether such indices were useful in predicting outcome; (b) the completeness
      of microbiological testing and whether maximizing the number of specimens sent to
      the laboratory would increase the frequency of positive microbiological diagnoses
      and; (c) the influence of the above on clinical management. Forty-eight patients
      with consolidation on chest X-ray were studied in two audit periods: 1 February
      1991 to 1 May 1991 and 2 May 1991 to 16 March 1992. After the first audit period,
      a rubber stamp with a check list of microbiological investigations was used in
      the patients' notes. Seven 'markers of severity' of pneumonia, were recorded
      consistently throughout the study and these were useful in predicting outcome (P
      < 0.01). In the first audit period sputum culture, blood culture and acute
      serology were recorded in approximately 50% of patients. Following the
      introduction of the rubber stamp, the requesting of sputum, blood and urine
      antigen rose from none in the first audit period to 40-60%. The increase in the
      number of specimens obtained was not associated with an increase in the
      proportion of positive microbiological diagnoses. Clinical management was altered
      in 10 patients because of the microbiological reports and in four patients with
      negative microbiology (chi2 = 8.19; P < 0.01). CONCLUSION: The standard of
      initial assessment was high in this specialist unit, and the presence of two or
      more 'markers of severity' did help predict outcome. A simple change in work
      practice resulted in a significant improvement in the thoroughness of
      microbiological investigations.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7809444
TI  - No effect of gender on lung mucociliary clearance in young healthy adults.
AB  - Lung mucociliary clearance (LMC) depends on age and it is adversely affected by
      cigarette smoking. When using the radioaerosol technique for measuring LMC the
      initial site of deposition of the radioaerosol within the lungs affects its rate
      of removal. Whether there is a difference in gender for LMC is still an open
      question. Forty-one (20 female, 21 male) healthy, non-smoking subjects had their
      lung mucociliary clearance measured using an objective, non-invasive radioaerosol
      technique. The male and female groups were closely matched for initial
      distribution of the radioaerosol. There was no statistical significant difference
      between males and females in the rate of clearance of inhaled radioaerosol over a
      6 h observation period. When comparing the LMC of two groups although it is
      important to match them for age, smoking habits and initial topographical
      distribution of the tracer radioaerosol it does not seem essential to also match
      the two groups for gender.

PMID- 7809445
TI  - Trypsin-triggered emphysema: an established model in rats.

PMID- 7809446
TI  - Urban deprivation and tuberculosis in the elderly.

PMID- 7809447
TI  - Acute respiratory failure due to bronchiolitis of unknown aetiology.

PMID- 7809448
TI  - Reversible myocardial ischaemia following vincristine containing chemotherapy.

PMID- 7809449
TI  - Primary malignant fibrous histiocytoma of the pleura. A case report and review of
      the literature.

PMID- 7809450
TI  - [Surgery of glaucoma: intrascleral trabeculo-irido encleisis].
AB  - The objective of this work is to appraise a surgical proposal for the treatment
      of glaucoma which attempts to avoid the relapses and complications. The technique
      consists of the fulfillment of a filtering blister (chamber of pressure
      derivation) using a support of corneoscleral trabeculae together with a support
      of iris placed into the sclera through a scleral flapping. 70 patients (125 eyes)
      with more than 7 years after surgery with this technique were selected at random.
      Their field of vision and eye pressure were evaluated and biomicroscopy and
      gonioscopy were practiced. The efficiency was of 95%, and patients with a field
      of vision between 10 and 20 degrees, and with pressures higher than 40 mmHg
      before surgery showed an improvement of an average of 5 degrees. The results are
      based on the successful endothelization of the accessory chamber achieved and in
      the building of a bond that stops the closing of the channel between the anterior
      and accessory chambers. The results of this long term follow-up suggest that the
      technique analyzed offers a good alternative to the surgery of glaucoma.

PMID- 7809451
TI  - [Eosinophilia in pediatrics. Report of clinical cases].
AB  - We present four clinical cases where eosinophilia was a prominent sign. Final
      Diagnoses were Toxocariasis, Ascaris Lumbricoides Infection, Acute Lymphocytic
      Leukaemia and Histiocytosis of Langerhans Cells.

PMID- 7809452
TI  - [Hyperlipoproteinemia in the production of atherosclerosis. Risk factors:
      diagnosis and treatment].

PMID- 7809453
TI  - [Histophysiology of the salivary glands in birds with different food regimens].

PMID- 7809454
TI  - [Bacterial infections of the skin. Impetigo: etiology and clinical aspects].
AB  - One hundred children with a clinical diagnosis of Impetigo are presented. Seventy
      of them were bacteriologically studied. The sign-symptomatology is that usually
      described in this type of affection. Streptococcus was the principal bacterium
      involved and predominated in the youngest patients. Males were more frequently
      affected. There were no complications which could be attributed to this pathology
      either by local extension or by immunological involvement.

PMID- 7809455
TI  - [Ethics and transplantation].

PMID- 7809456
TI  - [The indications and selection criteria for heart transplantation].

PMID- 7809457
TI  - [The role of echocardiography in the indications for heart transplantation].
AB  - Mono- and B-mode echocardiography is inferior to clinical evaluation and
      haemodynamic studies for timing of cardiac transplantation in idiopathic and/or
      ischemic cardiopathy. Some echo- and Doppler-derived variables are of prognostic
      significance as predictive guides in patients assessed for cardiac
      transplantation.

PMID- 7809458
TI  - [Infections in heart transplantations].
AB  - Infections are one of the most important problems in heart transplants
      recipients: they are responsible for half total mortality within one year after
      surgery and one third of mortality during the following period. Underlying
      medical illness of the host, lack of specific immunity, prior colonization are
      conditions that may contribute to infections after surgery: immunosuppression to
      contrast rejection or due to Cytomegalovirus (CMV) infection are other factors
      favoring infections. Lung infections are most frequent. During the first month
      after surgery microorganisms responsible are the same found in cardiosurgery
      patients, staphylococci and gram negative, and occasionally herpes simplex virus
      (ESV) reactivated infections occur. From the second to the sixth month most of
      the CMV and Toxoplasma infections occur, with some Pneumocystis and mycotic
      events. Both are so frequent that in a seronegative host a specific prophylaxis
      against CMV and Toxoplasma is regularly recommended. The very late period more
      than six month after surgery is characterized by common infections seen in any
      population, that may present in altered or more severe fashion due to immune
      suppression. Another late event is cryptococcal meningitis.

PMID- 7809459
TI  - [Cyclosporin in heart transplantations. The authors' personal experience].
AB  - The discovery of cyclosporine A (CsA) was a major development in the evolution of
      organ transplantation. In renal transplantation use of CsA improved graft
      survival such that HLA-matching is no longer as important and determinant as
      before. Liver transplantation prior to the arrival of CsA was almost abandoned by
      Starzl because of uncontrollable rejection. Hearth transplantation, after initial
      enthusiasm, was soon restricted to few centers as the difficulties in caring for
      these patients became apparent. Availability of CsA allowed more than 2500 hearth
      transplants to be performed annually today. At Stanford initially cardiac
      transplant survival at one year was 40% and at 5 years was approx 20%. The best
      results in patients treated with azathioprine-prednisone, just prior to the
      introduction of cyclosporine, were 65% and 40%. At present survival is 83% at 1
      year and 50% at 6-7 years, as in other active centers around the world. CsA is
      the first drug specifically developed to target immunocompetent T-lymphocytes,
      and is the gold standard model for other new drugs. Its action is modification of
      rejection, so that when it occurs it is less acute in onset and less fulminant.
      The prevalence and mortality of infections have also been reduced. The major
      drawback of cyclosporine is nephrotoxicity: all patients undergo a progressive
      decline in creatinine clearance and within one year 90% have hypertension. A
      second problem is post-transplant lymphoproliferative disease, that takes the
      form of an aggressive and potentially lethal B-cell lymphoma appearing most
      commonly within one year from surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7809460
TI  - [Pulmonary inflammation in systemic sclerosis. An assessment by bronchoalveolar
      lavage].
AB  - Interstitial pulmonary fibrosis is a common feature of systemic sclerosis (SS).
      Clinicopathologic observations suggest that interstitial and alveolar
      inflammation may appear prior to fibrosis. Using the bronchoalveolar lavage (BAL)
      technique, we have characterized the nature of the inflammatory process in the
      lower respiratory tract of 15 non-smoking scleroderma patients and compared the
      results with those found in eight normal subjects. Alveolitis was detected in 11
      patients (73%). Abnormalities in the cellular constituent included a significant
      increase of the proportion of lymphocytes (20.8 +/- 3.2 vs 8.1 +/- 1.2; p = 0.01)
      and neutrophils (3.3 +/- 0.8 vs 0.8 +/- 0.2; p = 0.04). T cell subsets, evaluated
      by flow cytometry, showed a significant increase of CD8+ T cells (36.6 +/- 3.2 vs
      25, 1 +/- 3.3; p = 0.04) and a decrease of CD4+/CD8+ ratio (1.1 +/- 0.1 vs 2.1 +/
      0.4; p = 0.04). Seven patients with an elevation of proportional BAL (lymphocyte
      count > 15%) had greater dyspnoea and chest radiographic score than patients
      without lymphocytic alveolitis (p = 0.02) and they had greater reduction in
      carbon monoxide diffusing capacity (DLco) (p = 0.04). Furthermore, a
      statistically significant correlation between the total lymphocyte cell count and
      the DLco (p = 0.03) was observed. Finally the stepwise multiple regression
      analysis identified lymphocyte count in lavage fluid as the predictor most
      strongly associated with an abnormal interstitial radiographic pattern (p =
      0.001). Our results report the notion that the lymphocytes, in addition to the
      macrophages and neutrophils, may play roles in the pathogenesis of lung injury.

PMID- 7809461
TI  - [Recurrent secretory otitis media and adenoidism. A retrospective study of the
      results observed with the medical and surgical therapy of 1250 children].
AB  - A retrospective study, between 1982 and 1993, on 1250 children with otitis media
      with effusion and hypertrophic adenoids was carried out. 1150 children were
      selected from those who had been administered S-carboxymethylcysteine-lysine for
      three months period, and antihistaminics, decongestants and anti-inflammatory
      drugs as concomitant treatment and 100 children from those who had undergone
      adenoidectomy. ORL-examination, audiometry and tympanometry, before and after the
      period of the therapy, were performed. No significant differences were found
      between the two groups with a percentage of successful outcome of 77-79%. On the
      basis of the data obtained, the tendency of avoiding surgical management by using
      the appropriate pharmacological therapy is underlined, particularly taking into
      consideration the safety profile of the medical treatment.

PMID- 7809462
TI  - [Giant-cell arteritis. Comments on the case histories of 30 patients].
AB  - This survey deals with the main clinical aspects at the diagnosis and during the
      follow-up of thirty consecutive patients with giant-cell arteritis (temporal
      arteritis and rheumatic polymyalgia), controlled over a period of 15 years. The
      work aimed at verifying the diagnostic accuracy with regard to a more
      underestimated than rare disease. We believe that such a consideration is a
      useful introduction to a wider research into the epidemiological and biological
      aspects of the disease which are still to be determined.

PMID- 7809463
TI  - Early prognostic assessment of acute pancreatitis with sterile necrosis. A
      perspective clinical study.
AB  - In an attempt to early assess the prognosis of acute pancreatitis with sterile
      necrosis, we have perspectively studied 40 patients with necrotizing acute
      pancreatitis and sterile necrosis in the first 48 hours of disease. As prognostic
      parameters, we have considered the computed tomography score according to
      Balthazar, simplified prognostic criteria according to Agarwal, Glasgow criteria
      and C reactive protein. Patients were divided in A group, 5 patients who died,
      and B group, 35 patients who survived. Computed tomography score, simplified
      prognostic criteria and Glasgow criteria were significantly higher in A group
      than B (9.5 +/- 1 vs 6.3 +/- 1.9, 3.6 +/- 0.5 vs 1.2 +/- 1.2 and 5.4 +/- 1.7 vs
      2.7 +/- 1.9 respectively); conversely, C reactive protein serum levels did not
      show significantly difference in the two groups. We conclude that the extension
      of pancreatic and extrapancreatic necrosis, as measured by computed tomography,
      as well as the failure of extrapancreatic organs and the development of systemic
      and metabolic complications, as assessed by simplified prognostic score and
      Glasgow criteria, are the most important determinant of prognosis in necrotizing
      acute pancreatitis with sterile necrosis.

PMID- 7809464
TI  - Positive responses to clonidine test in nephrovascular hypertension: only a false
      positive?

PMID- 7809465
TI  - [Prolymphocytic leukemia: the therapeutic strategy].
AB  - Prolymphocytic leukemia (PLL) is a malignant lymphoproliferative disorder,
      characterized by massive splenomegaly, predominance of prolymphocytes in the
      peripheral blood and bone marrow, minimal lymph nodes enlargement and poor
      prognosis. It accounts for a 5-10% case of chronic lymphocytic leukemia (CLL).
      Patients age is usually over the fifth decade, the disease is 4.1 more common in
      males. More than 80% are B-lymphocytic derived cells showing a post-thymic
      phenotype. Median survival of B-PLL patients is 3 years, while only 7 months in T
      PLL. Standard therapy of CLL with alkylating agents and prednisone have been not
      much effective in the treatment of PLL with a response rate of about 20%. Up to
      date no ideal treatment is available for PLL. A realistic goal is probably to
      achieve a clinical course transformation, from aggressive to mild, thus changing
      from short to long term prognosis. For this purpose the initial therapeutic
      approach cannot be limited to a single agent only. Splenic irradiation, intensive
      anthracyclines-based regimens, leukapheresis combine together represent the best
      therapeutic choice. Alkylating agents with or without prednisone may play a role
      in keeping indolent clinical course. Fludarabine has shown antileukemic activity
      against PPL even in patients resistant.

PMID- 7809466
TI  - Laboratory and clinical aspects of the Mycobacterium avium epidemic: contributing
      factors associated with variability of drug susceptibility and immune
      responsiveness, and the multifaceted nature of pathogenicity.

PMID- 7809467
TI  - Epidemiology of Mycobacterium avium infections in the pre- and post-HIV era.

PMID- 7809468
TI  - Mycobacterium avium infections in animals.

PMID- 7809469
TI  - Development of rapid techniques for identification of M. avium infections.

PMID- 7809470
TI  - Prevention and treatment of Mycobacterium avium complex infection.

PMID- 7809471
TI  - Quantitative cultures and drug susceptibility testing of Mycobacterium avium
      clinical isolates before and during the antimicrobial therapy.

PMID- 7809472
TI  - Clinical trials in Mycobacterium avium therapy: lessons to take home.

PMID- 7809473
TI  - Practical issues in the antibiotic and immunotherapy of Mycobacterium avium
      disease in immunocompromised patients.

PMID- 7809474
TI  - Genetic aspects of drug resistance in Mycobacterium avium.

PMID- 7809475
TI  - Contributions of animal and macrophage models to the understanding of host
      parasite interaction of Mycobacterium avium complex (MAC) disease.

PMID- 7809476
TI  - Immunomodulatory events in Mycobacterium avium infections.

PMID- 7809477
TI  - Mycobacterium avium: pathogenicity in HIV1 infection.

PMID- 7809478
TI  - Molecular basis of colony morphology in Mycobacterium avium.

PMID- 7809479
TI  - Cell envelope constituents and the multifaceted nature of Mycobacterium avium
      pathogenicity and drug resistance.

PMID- 7809480
TI  - Clinical and laboratory investigations of active compression-decompression
      cardiopulmonary resuscitation.
AB  - Based upon an anecdotal report of successful resuscitation using a toilet
      plunger, Cohen and co-workers have developed and investigated a hand-held suction
      cup as an adjunct to standard manual CPR. This new method, called active
      compression-decompression cardiopulmonary resuscitation, utilizes a device which
      is placed over the mid-sternum, approximately 1-2 inches above the lower rib cage
      border. Active compression-decompression cardiopulmonary resuscitation is then
      performed in accordance with American Heart Association guidelines at a rate
      equal to 80-100/min using a 50% duty cycle and compression depth of 1.5-2.0
      inches. Initial studies using the ACD device in both models and human subjects
      late after cardiac arrest have demonstrated improved cardiopulmonary hemodynamics
      when compared to standard manual CPR. Transophageal echocardiographic studies in
      human subjects have shown increased left ventricular filling during active
      decompression suggesting that active chest decompression improves venous return
      to the heart thus increasing left ventricular volume and stroke volume. Improved
      resuscitation success has also been documented in human subjects after in
      hospital and pre-hospital cardiac arrest. Active compression-decompression
      cardiopulmonary resuscitation is a simple method which utilizes a hand held
      suction cup as an interface between rescuer and victim during closed chest
      circulatory support. This method allows for standard manual cardiopulmonary
      resuscitation with the addition of active chest wall decompression and appears to
      be a beneficial adjunct to standard manual cardiopulmonary resuscitation.

PMID- 7809481
TI  - Prediction of failure to survive following in-hospital cardiopulmonary
      resuscitation: comparison of two predictive instruments.
AB  - The purpose of this study is to compare two clinical predictive rules, the pre
      arrest-morbidity (PAM) index and the prognosis-after-resuscitation (PAR) score,
      which predict failure to survive following in-hospital cardiopulmonary
      resuscitation (CPR). The study population consisted of 274 consecutive adult
      patients who underwent CPR at University College Hospital in Galway, Ireland over
      a 2-year period. The PAM and PAR scores were calculated from the most recent data
      available for each variable prior to cardiac arrest. Performance of the
      predictive scores was compared using Student's t-test, Pearson chi-square,
      Fisher's exact test, and receiver-operating characteristic (ROC) curves where
      appropriate. The PAM index identified 23 patients with a score > 4, while the PAR
      score identified 59 patients with a score > 5, none of whom survived. The
      sensitivity of the PAR score for the prediction of failure to survive was 23.7%,
      while that of the PAM index was 9.2%; neither index incorrectly identified a
      patient as a non-survivor who eventually survived. The PAR score also had a
      greater area under the ROC curve, although this difference was not statistically
      significant (P = 0.07). In summary, the PAR score performed better than the PAM
      index in the identification of patients who are unlikely to survive following
      CPR. Although further confirmation is necessary, it may provide useful prognostic
      information to physicians and patients involved with decisions about do-not
      resuscitate orders.

PMID- 7809482
TI  - Predictors of early and late survival after out-of-hospital cardiac arrest in
      which asystole was the first recorded arrhythmia on scene.
AB  - BACKGROUND: A large proportion of patients who suffer out-of-hospital cardiac
      arrest have asystole as the initial recorded arrhythmia. Since they have a poor
      prognosis, less attention has been paid to this group of patients. AIM: To
      describe a consecutive population of patients with out-of-hospital cardiac arrest
      with asystole as the first recorded arrhythmia and to try to define indicators
      for an increased chance of survival in this population. SETTING: The community of
      Gothenburg. PATIENTS: All patients who suffered out-of-hospital cardiac arrest
      during 1981 to 1992 and were reached by our emergency medical service (EMS)
      system and where cardiopulmonary resuscitation (CPR) was attempted. RESULTS: In
      all there were 3434 cardiac arrests of which 1222 (35%) showed asystole as the
      first recorded arrhythmia. They differed from patients with ventricular
      fibrillation by being younger, including more women and having a longer interval
      between collapse and arrival of the first ambulance. In all 90 patients (7%) were
      hospitalized alive and 20 (2%) could be discharged from hospital. Independent
      predictors for an increased chance of survival were: (a) a short interval between
      the collapse and arrival of the first ambulance (P < 0.001) and the time the
      collapse occurred (P < 0.05). Initial treatment given in some cases with
      adrenaline, atropine and tribonate were not associated with an increased
      survival. CONCLUSIONS: Of all the patients with out-of-hospital cardiac arrest,
      35% were found in asystole. Of these, 7% were hospitalized alive and 2% could be
      discharged from hospital. Efforts should be made to improve still further the
      interval between collapse and arrival of the first ambulance.

PMID- 7809483
TI  - Sudden cardiac death of a teenage girl.
AB  - Anomalies of coronary artery origin can be of little clinical significance and
      only an incidental autopsy finding. However recent case reports have shown that a
      wide range of potential pathologic alterations of congenital coronary anomalies
      are associated with clinical symptoms and exercise related sudden death. We
      describe the case of a 16-year-old girl who sustained a cardiac arrest and died
      after cardiopulmonary resuscitation (CPR) of intractable cardiogenic shock. The
      sporty and previously healthy girl suddenly fainted after swimming in a tributary
      of the Danube. Autopsy revealed an anomalous origin of the left coronary artery
      from the anterior sinus of Valsalva and its course between aorta and pulmonary
      artery. The cause of this anomalous origin and possible mechanism for sudden
      death is discussed. We conclude that this congenital anomaly should be considered
      in cases of major cardiac events in young people.

PMID- 7809484
TI  - A major "minor coronary anomaly".

PMID- 7809485
TI  - Bolus injection of thrombolytic agents during cardiopulmonary resuscitation for
      massive pulmonary embolism.
AB  - Thrombolytic therapy has proved to be efficacious in the treatment of massive and
      fulminant pulmonary embolism (PE), but thrombolysis has been considered as
      contraindicated during cardiopulmonary resuscitation (CPR). This review on the
      administration of thrombolytic agents in patients who have suffered massive PE
      necessitating CPR summarises 14 anecdotal reports and three case series involving
      34 patients. The case series revealed an overall initial survival rate of 55-100%
      following bolus administration of thrombolytic agents. In general, bleeding
      complications were managed conservatively. The establishment of the diagnosis may
      be feasible using echocardiography or bedside angiography during CPR. However,
      therapeutic measures should be taken without delay; the patient's history and the
      clinical picture may thus be the only diagnostic criteria. Even where myocardial
      infarction is misinterpreted as PE during CPR, bolus injection of a thrombolytic
      agent can be an appropriate therapeutic option. An alternative may be mechanical
      catheter fragmentation of the thrombus with subsequent local thrombolysis.
      Surgery may be restricted to hospitals with ready access to extracorporeal
      circulation. We conclude that early administration of thrombolytic agents during
      PE necessitating CPR may help to reduce mortality. We favour the administration
      of urokinase (2- to 3,000,000-U bolus) or rt-PA.

PMID- 7809486
TI  - Simultaneous active compression-decompression and abdominal binding increase
      carotid blood flow additively during cardiopulmonary resuscitation (CPR) in pigs.
AB  - The effects of adding active compression-decompression and abdominal binding
      separately or combined to standard compression CPR was tested in a randomized
      cross-over design during ventricular fibrillation in eight pigs. The flow and
      pressure effects of the two techniques appeared to be additive with no
      interference between the two. Carotid blood flow increased 22% with active
      compression-decompression, 34% with abdominal binding and 59% with the
      combination compared to flow with standard compression. Peak antegrade carotid
      flow occurred in early systole with retrograde flow in early diastole and close
      to zero in late diastole with no profound alterations induced by active
      decompression or abdominal binding. Abdominal binding increased the intrathoracic
      pressure during the compression phase as estimated from the esophageal pressure,
      while active decompression caused a negative esophageal pressure during the
      decompression phase. Neither active decompression nor abdominal binding caused
      any changes in the coronary perfusion pressure, nor in the left ventricular
      transmural pressure except for a rise in mid-diastolic pressure with active
      decompression.

PMID- 7809487
TI  - Oxygen dynamics and induced hypothermia in sepsis.

PMID- 7809488
TI  - Defibrillation by nurses.

PMID- 7809489
TI  - Prognostic markers in patients with severe accidental hypothermia.

PMID- 7809491
TI  - A comparison of Blau's syndrome and sarcoidosis.
AB  - Blau's syndrome is a familial multisystem granulomatous inflammation which may be
      confused with childhood sarcoidosis because it presents with iridocyclitis,
      posterior uveitis, granulomatous skin disease, arthritis and elevated serum
      angiotensin-converting enzyme. They are distinguished by the absence of pulmonary
      involvement and a negative Kveim-Siltzbach skin test.

PMID- 7809490
TI  - Hypothermia in acute blunt head injury.
AB  - Mild to moderate hypothermia has been employed since the 1940s in the treatment
      of acute blunt head trauma. The utility of hypothermia in ischemic injury has
      been confirmed, by both animal studies and clinical experience, in cardiovascular
      and neurological surgery. In blunt injury, though, only one prospective,
      randomized study has shown a statistically significant improvement in long term
      outcome. Clinical experience, animal data, proposed mechanisms, technical
      considerations, and potential risks are reviewed. Hypothermia remains
      controversial in the setting of blunt head injury but may prove to be a useful
      treatment modality.

PMID- 7809492
TI  - Soluble interleukin-2 receptor in blood from patients with sarcoidosis and
      idiopathic pulmonary fibrosis.
AB  - Soluble interleukin-2 receptor (sIL-2R) concentration is considered to reflect
      disease activity in patients with sarcoidosis. However, it remains to be
      evaluated whether or not the sIL-2R concentration reflects the total burden of
      granulomatous lesions, or if it can be a useful marker for other interstitial
      lung diseases such as IPF, the lesions of which are restricted to the lungs. In
      this study, we demonstrated that sIL-2R concentrations in 16 patients with active
      sarcoidosis increased (2031 +/- 1222 U/ml), compared to those in 29 patients with
      inactive disease (796 +/- 313), 24 with IPF (859 +/- 694) and 33 healthy controls
      (467 +/- 174). sIL-2R concentrations in patients with IPF also increased, more
      than those in healthy subjects. sIL-2R concentrations in 10 patients with
      extrathoracic lesions (ETL) were not different from those in 6 patients without
      ETL. Correlation between serum sIL-2R concentrations and serum ACE activity, BAL
      macrophage %, and BAL lymphocyte % was shown in patients with sarcoidosis. In
      patients with IPF, a correlation between sIL-2R concentrations and BAL macrophage
      % was found but there was no correlation between sIL-2R concentrations and BAL
      lymphocyte %. In conclusion, serum sIL-2R concentrations seem to reflect total
      inflammatory lesions. In addition, they reflect total inflammatory lesions of the
      lungs in sarcoidosis and IPF. For clinical purposes, its measurement may be more
      useful than that of BAL fluid concentrations in patients with sarcoidosis and
      IPF.

PMID- 7809493
TI  - Epidemiological study on sarcoidosis in Moravia and Silesia.
AB  - Standard epidemiological and clinical features of sarcoidosis were evaluated in
      24 regional centres from Moravia and Silesia (4 million inhabitants). During 1981
      1990 the incidence ranged from 3.3 to 4.4/100,000 with slight decrease after
      1985, when unselected chest X-ray screening was restricted. The prevalence
      (however disputable in sarcoidosis) increased from 41.3 to 63.1/100,000. Sex
      ratio male/female was 1: 2.35; only 39% of patients were younger than 40 years.
      Biopsy supported the diagnosis in 60% of cases. Tuberculin negativity was found
      in 64%. X-ray types were presented as follows: 0-2%, I-71%, II-22%, III-5%.
      Regional incidences varied from 0.9 to 11.7/100,000. Lower values were found in
      mining areas and high pneumoconiosis incidence. The course of the disease was
      benign with only sporadic extrapulmonary complications or pulmonary fibrosis. The
      results indicate that improved knowledge of sarcoidosis has brought
      epidemiological equilibrium to the evaluated area.

PMID- 7809494
TI  - Prognosis after pacemaker implantation in cardiac sarcoidosis in Japan. Clinical
      evaluation of corticosteroid therapy.
AB  - Corticosteroids (CS) are useful drugs for the treatment of cardiac sarcoidosis
      with severe conducting defects due to sarcoid granuloma. Despite the continuous
      administration of CS, many patients with severe cardiac involvement may
      eventually die of congestive heart failure. The purpose of this study was to
      evaluate the efficacy of CS in patients who had a pacemaker implanted.
      Questionnaires were obtained from 29 institutes, and 34 cardiac sarcoidosis
      patients (8 males and 26 females) with pacemaker implantation were enrolled in
      this survey. We analyzed the survival period in these patients by the Kaplan
      Meier method. There was no statistically significant difference in the survival
      of these patients in terms of their age, sex or disease duration (time from the
      onset of sarcoidosis to cardiac involvement). However, their survival was
      affected by the grade of dyspnea, the presence of heart failure, and certain
      abnormal findings on a myocardial scintigram and echocardiogram. In order to
      evaluate the effect of CS on the prolongation of survival, we measured the
      survival of the patients treated with CS and those not treated with CS. However,
      because of the small number of patients not treated with CS, we were unable to
      detect any statistically significant difference in survival. Therefore, we
      analyzed 104 cases in order to evaluate CS therapy: the 34 cases from the
      questionnaires and 70 cases reported in the literature over the last 10
      years.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7809496
TI  - Respiratory symptoms at presentation and long-term vital prognosis in patients
      with pulmonary sarcoidosis.
AB  - A follow-up of 254 patients with pulmonary sarcoidosis has been carried out after
      a median of 27 years from the diagnostic admission. Information on respiratory
      symptoms at entry was available in 80% of the patients. Cough and chronic
      bronchitis was present in 39% and 37%, respectively, whereas 41% reported
      breathlessness when walking and 25% reported breathlessness when undressing. In
      total, 51% had at least one respiratory symptom. All patients could be traced;
      eighty patients (31.5%) died during follow-up. A total of 17 died of sarcoidosis
      and a further 16 died of sarcoidosis-related diseases. All deaths from
      sarcoidosis were seen among patients with respiratory symptoms at presentation.
      For sarcoidosis and sarcoidosis-related deaths (N = 33), presence of one or more
      of the respiratory symptoms increased the risk significantly. For overall
      mortality, respiratory symptoms were also significant predictors; this was the
      case even after adjusting for age, sex, x-ray stage and lung function (FEV1 &
      TLC) at presentation. In conclusion, respiratory symptoms at the time of
      diagnosis are independently related to vital prognosis in pulmonary sarcoidosis.

PMID- 7809495
TI  - Aspecific bronchial hyperreactivity in pulmonary sarcoidosis.
AB  - Aspecific bronchial hyperreactivity (A.B.H.) is a condition found mostly in cases
      of bronchial asthma, but it may also present in other pathologies affecting the
      respiratory tract. This study examines 30 patients presenting hilo-pulmonary
      sarcoidosis, 27 asthmatic patients and 25 healthy subjects as controls. The three
      groups were sex and age matched. No significant difference in smoking habits
      between controls and sarcoidosis patients was found. Patients were tested for
      aspecific bronchial hyperreactivity by administering increasing doses of
      methacholine. Methacholine inhalation was performed following a dosimetric
      method. Aspecific bronchial hyperreactivity was found in 6 (20.6%) of sarcoidosis
      patients with a significant frequency (p < 0.05). No statistically significant
      difference was found for mean PD20FEV1 values, but the difference between asthma
      and sarcoidosis patients was highly significant (p = 0.003). No statistically
      significant difference was found between basal FEV1 means expressed as a
      percentage of the former in asthmatics and sarcoidosis patients, both responsive
      and unresponsive. Although it is difficult to draw conclusions from these
      findings, aspecific bronchial hyperreactivity was seen to increase in subjects
      with sarcoidosis, and this may explain the not rare association between asthma
      and sarcoidosis.

PMID- 7809497
TI  - Inhaled budesonide for maintenance treatment of pulmonary sarcoidosis.
AB  - Forty-seven patients with pulmonary sarcoidosis stage II-III, fulfilling clinical
      indications for starting treatment with corticosteroids, received oral
      methylprednisolone for 8 weeks in gradually decreasing doses (starting dose 48 mg
      per day). From week 5 onwards, they also received inhaled budesonide, 1.6 mg
      daily. Treatment was continued for 18 months and all patients have been followed
      for at least 3 years. At 18 months treatment could be discontinued in 38
      patients, who had used individually adjusted doses of budesonide depending on the
      clinical response (reduced doses in 14, initial dose in 16, and increased doses
      in 8 patients). Budesonide treatment alone was satisfactory in 31 of these 38
      cases. An additional seven patients could stop treatment after receiving
      supplementary courses of oral steroids for 3-12 months. Treatment is ongoing in 9
      patients in which 6 have extrapulmonary manifestations requiring oral steroids.
      The chest radiograph became normal in 22 patients and improved in 14. Significant
      improvements were noted in FVC and DLco in relation to predicted normal values.
      Serum ACE, lysozyme and beta 2-microglobulin values decreased significantly.
      Transient cough was seen in 5 and hoarseness in 3 patients. No systemic side
      effects were noted; one patient taking 2.4 mg budesonide daily had a plasma
      cortisol value below the normal range. Inhaled budesonide seems to offer an
      effective and safe alternative to oral steroids for long-term maintenance
      treatment of patients with pulmonary sarcoidosis.

PMID- 7809498
TI  - Malignant T cell lymphoma associated with sarcoidosis.
AB  - We report an unusual case of non-Hodgkin T cell lymphoma associated with
      sarcoidosis. A 44-year-old woman was histologically diagnosed as having
      sarcoidosis in 1966. Diffuse interstitial lung disease and erythematous skin
      nodules disappeared following steroid therapy. Twenty years after sarcoidosis
      onset erythematous nodosum recurred and biopsy specimens revealed non caseating
      epithelioid granuloma. Thirty-seven months later a malignant T cell lymphoma
      developed in the skin portion where sarcoid lesions recurred. We discuss the
      possible relationship between the sarcoid inflammatory process and the
      development of a malignant T cell clone as origin of the T cell lymphoma.

PMID- 7809499
TI  - Sarcoid pleural effusion: a report of two cases.
AB  - Two patients with pleural effusions have been seen among 270 patients with
      sarcoidosis in an eighteen-year period. In both patients pleural effusions were
      present at the onset of sarcoidosis and associated with extensive pulmonary or
      extrathoracic involvement. Pleural effusions were exudative with a high
      lymphocyte count. One patient was successfully treated with corticosteroids and
      the second died from cardiac complications of the disease.

PMID- 7809500
TI  - Pleural effusion in sarcoidosis: a case report.
AB  - Pleural effusion is a well-recognized clinical entity that can be associated with
      sarcoidosis. Nevertheless, the real prevalence of this phenomenon remains to be
      established. This study describes the case of a 57-year-old male sarcoid patient
      who presented with right exudative pleural effusion, dyspnea on exertion, and
      bilateral pulmonary interstitial infiltrates. Sarcoidosis was diagnosed more than
      2 years prior to the onset of pleural involvement. Pleural biopsy revealed the
      presence of typical sarcoid non caseating granulomas. Sarcoid involvement of the
      pleura resolved following a 1-month course of high doses of steroids and did not
      recur during a 18-month follow up. When we retrospectively analyzed clinical data
      obtained from 624 consecutive sarcoid patients who were referred to our hospital
      between January 1980 and June 1993 and examined for the presence of pleural
      involvement, the only patient who showed pleural effusion and histologically
      proven sarcoidosis of the pleura was the case here described. The frequency of
      the phenomenon in our series is 0.16%. We conclude that pleural effusion
      represents a rare event in sarcoidosis.

PMID- 7809501
TI  - Childhood sarcoidosis presenting with hypercalcaemic crisis.
AB  - We report a case of hypercalcaemic crisis due to sarcoidosis in a 15-year-old
      boy. The clinical suspicion of sarcoidosis was confirmed by a liver biopsy. At
      admission serum calcium, 1,25(OH)2 and ACE were elevated and iPTH was suppressed.
      The levels of serum total and ionized calcium, iPTH, ACE, 1,25(OH)2 and 25-OH
      were followed and chest X-ray and pulmonary function tests were performed during
      systemic steroid treatment. The clinical condition improved during treatment and
      the paraclinical measurements normalised within 5 weeks. The mechanism whereby
      hypercalcaemia occurs in childhood sarcoidosis is clarified.

PMID- 7809502
TI  - The radiology of sarcoidosis.
AB  - Sarcoidosis is a multisystem granulomatous disease of unknown aetiology. The role
      of radiology is not only to support the clinical diagnosis but also as an adjunct
      to monitor the course and progression of the disease. The cornerstone of
      radiological assessment is the plain radiograph, however newer imaging methods
      are producing more information in relation to the anatomical distribution and
      pathophysiology which may ultimately have a profound effect on the management of
      this protean disease.

PMID- 7809503
TI  - Retinoblastoma.
AB  - Retinoblastoma (RB) is the most common intraocular malignancy of childhood,
      occurring in approximately 1 in 20,000 live births. It arises from pluripotential
      retinal progenitor cells. Mutations of the RB1 gene interfere with regulation of
      the cell cycle. Patients who harbor a germinal mutation of the RB1 gene are at
      risk for the development of second, non-ocular tumors.

PMID- 7809504
TI  - Pathology of neuroblastic tumors.
AB  - Histogenesis, basic histologic features, nomenclature, and criteria for diagnosis
      and prognostic classifications based on morphological features of neuroblastic
      tumors (NTs) are described. NTs that arise from neuroectodermal cells of the
      adrenal medulla and sympathetic ganglia recapitulate the development of
      sympathetic ganglion. The following three basic types of NTs are recognized:
      neuroblastoma (NBs) and ganglioneuroblastomas (GNBs) and ganglioneuromas (GNs).
      NBs can be undifferentiated, poorly differentiated or differentiating; GNBs have
      the following three subtypes. (1) nodular, (2) intermixed, and (3) borderline.
      The conventional and recommended terminology and Shimada terminology of NTs are
      described (Tables 1 and 2). There are three basic pathologic components of NTs,
      neuroblastomatous, ganglioneuromatous, and intermediate components (Figs 3, 5,
      and 7). There are two major prognostic classifications based on morphological
      features of NTs, Shimada classification and histologic grading (Tables 3 and 4).

PMID- 7809505
TI  - Molecular pathology of human neuroblastomas.
AB  - Several genetic features have been identified that are characteristic of
      neuroblastomas. These include hyperdiploidy, deletion of 1p, amplification of N
      myc, and expression of the neurotrophin receptor, TRK-A. These genetic
      characteristics allow neuroblastomas to be categorized into three subtypes, with
      distinct clinical features and behavior. In the past, neuroblastoma had been
      considered to be a disease with a better outcome if diagnosed early. However, it
      is now apparent that the tumors occurring in infants are genetically different
      than those in older children, and a genetically favorable subtype seldom, if
      ever, evolves into an unfavorable one. Different approaches may be necessary for
      each subtype, and the molecular pathology of the tumor may be better at
      predicting outcome than patient age and disease stage.

PMID- 7809506
TI  - Nephroblastoma (Wilms' tumor): a model system of aberrant renal development.
AB  - Wilms' tumor, or nephroblastoma, is a developmental malignancy of the kidney that
      affects approximately 1 in 10,000 children between 1 and 6 years of age.
      Typically, the histology of nephroblastoma reveals a disorganized renal
      developmental process showing blastema and epithelia randomly interspersed in
      varying amounts of stroma. This developmental disruption is associated with the
      loss of function of the tumor suppressor gene WT-1. This gene, located on
      chromosome 11 at band p13, codes for a zinc finger protein that may act as a
      transcriptional repressor. Familial cases of Wilms' tumor fit Knudson's "two hit"
      model, according to which a germ line mutation of one WT-1 allele predisposes to
      the tumor while an additional somatic mutation of the other allele causes
      malignant transformation. Originally proposed for retinoblastoma, this model
      defines the nature of the tumor suppressor gene as a gene that is tumorigenic
      when inactivated. However, not all Wilms' tumor cases fit this model because the
      majority of Wilms' tumors do not show a mutation of WT-1. For Wilms' tumor, the
      loss of tumor suppression appears to be more complex than for retinoblastoma.
      Some of the mechanisms recognized to date involve dominant negative WT-1
      mutations, interaction of the WT-1 gene product with other mutated transcription
      factors such as p53, loss of imprinting, and mutations of other tumor suppressor
      genes at 11p15 or other loci. Although classic Wilms' tumor is associated with
      good prognosis (85% survival), its anaplastic form is often fatal. Despite the
      plethora of knowledge gained in recent years, Wilms' tumor remains the center of
      attention for further investigation because it offers opportunities for studying
      normal kidney development, for understanding the molecular basis for clinically
      important anaplastic forms, as well as for elucidating the molecular mechanisms
      of tumor suppressor genes. To facilitate this task, Wilms' tumor
      heterotransplants have been established in nude mice. This provides an indefinite
      source of tumor tissue and a means to test their growth properties in response to
      drug treatments or molecular genetic manipulations. Furthermore, the
      establishment of stable Wilms' tumor cell lines is essential to investigating
      further the molecular basis of tumorigenesis using recombinant DNA technology.

PMID- 7809507
TI  - Hepatoblastoma.
AB  - Hepatoblastoma is the most frequently occurring liver tumor in children,
      accounting for over 25% pediatric hepatic tumors and nearly 50% of those that are
      malignant. Histologically, the tumor can be divided into the following six
      patterns: (1) fetal epithelial; (2) embryonal and fetal epithelial; (3)
      macrotrabecular; (4) small cell undifferentiated; and (5) mixed epithelial and
      mesenchymal type with teratoid features or (6) without teratoid features.
      Immunohistochemical studies display a wide variety of immunostaining with
      monoclonal antibodies particularly those specific for epithelial-derived
      components. Tumor cytogenetics show a high incidence of trisomy 20 and trisomy of
      all or part of chromosome 2. The developing liver displays many features similar
      to those seen in hepatoblastoma, including uniform hepatocytes and cords two
      cells thick separated by sinusoids displaying hematopoiesis. Hepatoblastomas
      display only minimal ductular differentiation, similar to the fetal development
      of the liver that does not display significant ductular development until well
      into the second trimester.

PMID- 7809508
TI  - Pleuropulmonary blastoma is THE pulmonary blastoma of childhood.
AB  - Pulmonary blastoma was defined by Spencer and others as a neoplasm with
      histopathological features thought to be reminiscent of Wilms' tumor. Unlike the
      other embryonal-fetal neoplasms that typically occur in early childhood, the
      majority of pulmonary blastomas have been reported in adults. One explanation
      offered by Spencer for the delayed clinical presentation of pulmonary blastoma is
      the continued development of lung parenchyma well past the postnatal period. It
      has been proposed that the pulmonary blastoma is a variant of carcinosarcoma,
      which is seen almost exclusively in adults. The classic pulmonary blastoma is
      described as a neoplasm with a mixture of primitive tubular profiles, immature
      blastema, and a spindle cell stroma. More recently, some have included the well
      differentiated adenocarcinoma of fetal type as a pure epithelial expression of
      pulmonary blastoma. By contrast, most cases of pulmonary blastoma in children
      have been described as having an exclusive mesenchymal composition, either
      embryonal rhabdomyosarcoma or a complex, mixed blastematous and sarcomatous
      neoplasm. Some pulmonary blastomas in children, particularly those with only
      embryonal rhabdomyosarcoma, have presented as a peripheral multicystic lesion
      that has been interpreted as a developmental cyst, either cystic adenomatoid
      malformation or bronchogenic cyst. Other tumors have been described as
      intrathoracic and anatomically separate from the lung, like some extralobar
      sequestrations. We have proposed the designation pleuropulmonary blastoma for
      these pulmonary or extrapulmonary neoplasms of childhood. We propose that this
      neoplasm is the rightful pulmonary blastoma rather than the pulmonary blastoma of
      Spencer, which has been the long-time pretender to the title.

PMID- 7809509
TI  - Pancreatoblastoma and solid and cystic papillary tumor: two tumors related to
      pancreatic ontogeny.
AB  - Two tumors of the pancreas are related to pancreatic ontogeny. The
      pancreatoblastoma is a tumor of children, more commonly boys than girls and
      progresses with a slow, sluggishly malignant course. Surgery successfully
      controls the disease in about half the cases. Morphologic and immunohistochemical
      studies reveal undifferentiated areas, ductular areas, acinar areas, and
      occasionally neuroendocrine differentiation. Very characteristic is the presence
      of nodules of squamous epithelium. These features reflect the potencies of the
      pancreatic anlage somewhat earlier than the fourteenth week of development. The
      solid and cystic papillary epithelial tumor of the pancreas is a tumor of
      adolescent and young adult females, often non-Caucasian. Surgical excision is
      often successful, but deaths from local persistence and metastases have been
      described. These tumors have features of ductulo-acinar neoplasms of uncommitted
      pancreatic primordia exceptionally with neuroendocrine differentiation.

PMID- 7809510
TI  - Medulloblastoma.
AB  - The histogenetic approach to the classification of embryonal tumors of the
      central nervous system has historically received wide acceptance as a scheme for
      histologic typing and nosologic definition. Medulloblastoma is a paradigm of a
      neuroblastic neoplasm whose origins and differentiation potential are traceable
      to cerebellar embryogenesis. Medulloblastomas show unequivocal neuroblastic
      maturational changes evidenced by neuritogenesis and expression of neuronal
      cytoskeletal and other neuronal differentiation-associated antigenic
      determinants. In addition, ganglion cells form in some lesions. Based on
      differential patterns of immunoreactivity for calbindin-D28k (a ventricular
      matrix (VM)-associated neuronal calcium binding protein, which is not expressed
      in the external granule layer (EGL) or its progeny) and the class III beta
      tubulin isotype (beta III) (expressed metachronously in the neuronal descendants
      of both neuroepithelia), it is possible that distinct subsets of medulloblastomas
      may implicate clonally-related neuroblasts from two sources: VM for classic
      medulloblastomas and the EGL for desmoplastic (nodular) medulloblastomas.
      However, the possibility of two separate origins for the classic medulloblastomas
      cannot be entirely excluded. Origin from the VM is suggested for the rare subset
      of medulloblastomas with ganglion cells. It is, however, unclear whether these
      ganglion cells are neoplastic (products of terminal neuronal differentiation), or
      dysplastic (entrapped preexisting elements of cerebellar heterotopias). Glial
      differentiation (gliomatous transformation) in medulloblastomas is at issue but
      is documented in rare cases of classic medulloblastomas (presumed heteroclones of
      cotransformed VM glial precursors), or desmoplastic medulloblastomas (probable
      stromal glial transformation-induction). Astrocytic proliferations in
      desmoplastic medulloblastomas may be stroma-derived (neuronal differentiation
      associated), analogous to Schwann cell contributions during maturation of
      peripheral neuroblastomas.

PMID- 7809511
TI  - Lipoblastoma: an embryonal tumor of soft tissue related to organogenesis.
AB  - The concept of embryomas or blastomas of connective tissues is difficult to
      define because of the usual association with a complex organ and typically
      malignant behavior. In the soft tissues, lipoblastoma is an example of a lesion
      which has a well-defined relationship to embryonic white fat and a capacity for
      differentiation. Its clinical behavior, however, is benign. This review discusses
      lipoblastoma in detail as an example of mesenchymal blastoma. Other potential
      mesenchymal blastomas and other primitive tumors of soft tissue with a capacity
      for differentiation are also mentioned.

PMID- 7809512
TI  - [The clinical estimate of adiposity is not a good predictor of insulin tissue
      sensitivity measured with a minimal model analysis].
AB  - Fifteen male volunteers, aged 30 to 40 years old, were classified according to
      body mass index (BMI) as lean (n = 5, BMI less than 20 kg/m2), normal (n = 5, BMI
      20-25) or obese (n = 5, BMI over 30). Glucose intolerance was ruled out by a
      normal oral glucose tolerance test and insulin sensitivity (SI) and glucose
      effectiveness (SG) were estimated by a minimal model analysis of a frequently
      sampled intravenous glucose tolerance test modified by an intravenous insulin
      injection at minute 20. The MINMOD program was fed with 29 or 12 values (reduced
      sampling schedule). Despite a significant inverse correlation between BMI and SI
      (r = -0.533 p < 0.05), the latter parameter overlapped among groups and the
      correlation was lost when obese individuals were not considered. Waist/hip ratio
      correlated modestly with SI (r = -0.52 p < 0.05). SG did not correlate with BMI.
      Using the reduced sampling schedule. SI values had a correlation coefficient of
      0.78 with those calculated using the usual sampling schedule, although they were
      82% lower. We conclude that only a BMI of over 30 accurately predicts a low SI,
      and that waist/hip ratio does not have a better predictive power.

PMID- 7809513
TI  - [Effect of insulin-like growth factor I on HLA-DR antigen expression in cultured
      human thyrocytes: a component of the autoimmune process?].
AB  - The aim of this study was to determine whether IGF-1 and INS are able to induce
      HLA-DR antigen expression (AgHLA-DR) in cultured human thyrocytes. Cytotoxicity
      assay in thyroid epithelial cells (cultured for 7 days to avoid spontaneous
      antigen expression) from 14 patients operated due to different thyroidal
      diseases, was used to assess HLA-DR expression. AgHLA-DR was reinduced adding IFN
      delta, IGF-1 or INS to the culture media, alone, combined or associated with TSH
      or TBII. Both IGF-1 and INS induced HLA-DR expression in a similar way as IFN
      delta did, and the response was enhanced with their combination, suggesting that
      they have different sites of action. Their association with TSH or TBII further
      augmented the response. To determine if IGF-1 acts via lymphocyte IFN-delta
      secretion, peripheral lymphocytes from 5 normal subjects were cultured with and
      without IGF-1 and the supernatant was used as stimulator, observing a stimulation
      similar to that induced by IFN-delta. This finding supports the hypothesis that
      IGF-1 acts stimulating a specific tyrosine kinase protein (p56 1ck) which is
      located in T lymphocyte receptors. According to our results we can conclude that,
      at least in vitro, both IGF-1 and INS play a role in the immune process, probably
      exerting a paracrine effect on autoimmunity, acting as perpetuating factors.

PMID- 7809514
TI  - [Determination of DNA content using cytophotometry in nuclear suspension
      conserved for prolonged periods (preliminary study)].
AB  - The variations in cytophotometric determination of DNA content were studied in a
      concentrated suspension of nuclei stored for prolonged periods. These came from
      normal and tumoral cells of an uterine leiomyosarcoma, fixed in formalin and
      included in paraffin. DNA was measured in normal and tumoral cells at days 0, 1,
      7, 11, 19, 27 and 33. No significant variations in DNA measurement were observed.
      In a same day, there was an uniform DNA content, ploidy pattern and DNA index and
      an aneuploid pattern was diagnosed in all histograms. These results suggest that
      nuclear suspensions can be conserved for long periods and used for DNA content
      determination, allowing the access of remote places to these techniques.

PMID- 7809515
TI  - [Efficacy of Chagas' disease vector control demonstrated through human
      infection].
AB  - The aim of this study was to assess the efficacy of Chagas disease vector control
      in Chile, using human disease as an index. After a twelve years control program
      using insecticides, dwelling infection in the IV region fell from 49 to 4%. In
      Combarbala (a community of the IV region) the infection rate, detected by
      indirect hemagglutination, immunofluorescence and ELISA tests, decreased from
      21.8% in 1986 to 8.2% in 1992 in primary school students (p < 0.001) and from 7.5
      to 5% in high school students. Besides the vector control program, no other
      important epidemiological changes occurred in this period, excepting some
      ecological changes.

PMID- 7809516
TI  - [Tropical spastic paraparesis (HAM/TSP) in different regions of the world.
      Subclinical and geographic differences in neurophysiologic studies].
AB  - Tropical spastic paraparesis is the same clinical entity all over the world. It
      has been suggested that some clinical presentation differences are due to not
      well defined environmental factors that act along with the virus, modifying the
      start and progression of the disease. We analyzed 25 publications on the disease
      coming from different parts of the world, aiming to unravel regional differences.
      In these reports, we found different degrees of subclinical abnormalities in
      visual and somatosensory evoked potentials, nerve conduction studies, superior
      and inferior limb F wave and electromyography. It is concluded that genetic,
      environmental and even cultural factors may influence the clinical presentation
      of tropical spastic paraparesis and explain the detected differences in the
      reports analyzed in this study.

PMID- 7809517
TI  - [Percutaneous mitral valvuloplasty and open mitral commissurotomy: comparison of
      2 techniques in immediate results].
AB  - The aim of this study was to assess the real usefulness of percutaneous mitral
      balloon valvuloplasty (PMV). Eighty patients aged less than 56 years old, with
      symptomatic pure mitral stenosis, with an hemodynamic and echocardiographic area
      < 1.5 cm2, without associated valvular or coronary lesions and without surgical
      contraindications were studied. These were randomized in two groups of similar
      age, sex, symptomatology, cardiac rhythm, severity of stenosis and valve anatomy,
      that were subjected to PMV (n = 38) using a double balloon technique or to mitral
      commissurotomy (n = 42) with extracorporeal circulation (MC). Mitral areas
      (calculated using modified Gorlin's formula) increased in 1.15 +/- 0.28 and 1.72
      +/- 0.34 cm2 in patients subjected to PMV and MC respectively. No patient died,
      there was one technical failure with PMV and two patients subjected to MC had a
      surgical wound infection. Mitral regurgitation increased in more than one degree
      in two patients treated with PMV (5%) and in 6 patients treated with MC (15%). It
      is concluded that PMV and MC are highly effective and safe procedures for the
      treatment of mitral stenosis. Mitral areas obtained with MC are higher than with
      PMV, however a significant improvement of the disease is achieved with both
      procedures and MC produces mitral regurgitation with a higher frequency.

PMID- 7809518
TI  - [Percutaneous mitral valvuloplasty: immediate and late results in 300 patients].
AB  - Between December 1987 and July 1992, we performed a balloon mitral valvuloplasty
      to 300 patients aged 48 +/- 23 years, with pure or predominant, symptomatic
      mitral stenosis, with an hemodynamic area < 1.5 cm2 and a mean echocardiographic
      score of 8.8 +/- 1.3 (6-13). Young subjects with mobile and flexible valves as
      well as elders with highly damaged valves were included. A transeptal technique
      employing 2 balloons was used in 97% of cases. There were 3 failures and 9
      deficient results. In 284 patients, the procedure was considered successful with
      a mean increase in mitral area (measured using modified Gorlin's formula) from
      0.88 +/- 0.13 to 2.19 +/- 0.38 cm2. Four patients died two due to a left
      ventricular traumatism, one due to an irreversible low cardiac output and one due
      to a massive systemic embolism. In five, a cardiac tamponade was treated with
      pericardiocentesis or surgery. One hundred patients were followed for a mean of
      40 +/- 3 months. Mitral areas remained over 1.5 cm2 in 87% and 14 had a
      significant reestenosis. The latter had an initial echocardiographic score over 8
      or previous surgical commissurotomy. Multifactorial analysis identified valvular
      motility and global echocardiographic scores as predictors of immediate success.
      Likewise, the last parameter and subvalvular thickening were predictors of late
      reestenosis and of increase in mitral regurgitation post valvuloplasty. According
      to our experience, percutaneous balloon mitral valvuloplasty is a first choice
      therapeutic alternative in patients with mitral stenosis.

PMID- 7809519
TI  - [Maternal age as a risk factor for congenital malformations].
AB  - We studied 131,899 consecutive births at the Maternity of the University of Chile
      Clinical Hospital, finding 4887 newborns with congenital malformations
      (representing a rate of 37.05 per 1000 alive newborns). Between January 1982 and
      December 1992 there were 41,344 births and 295 stillbirths (0.7%). Among the
      latter, 41 were malformed (13.9%). A graphic comparing the mean annual rates of
      malformations and maternal ages, shows a sustained increase in malformations form
      1972 to 1988, that decreases thereafter and stabilizes since 1982. There is a
      marked parallelism between the curves of malformation rates and maternal age (t21
      = 1.057, p < 0.1). It is concluded that the risk of congenital malformations
      increases along with maternal ages.

PMID- 7809520
TI  - [Focal hepatic lesions observed by echotomography with special reference to
      hydatidosis].
AB  - This article reports the results of 1080 ultrasonographic examinations of the
      liver in a clinic of the Ninth Region of Chile, using a SSD 620 Aloka equipment.
      In 61 examinations (5.6%) a focal liver lesion was found. Of these, 9 (14.7% of
      lesions) appeared as malignant (6 metastasis and 3 hepatomas) and 52 (85.3% of
      lesions) appeared as benign (10 inespecific calcifications of less than 10 mm, 6
      vascular lesions, 12 simple cysts, 2 cases of polycystic liver and 9 cases
      fulfilled Gharbi's criteria for hepatic hydatidosis). The diagnosis in these 9
      cases was confirmed by serology or surgery Thus, 14.7% of all focal lesions of
      the liver were due to hydatidosis. Considering that simple cysts are
      indistinguishable from hydatid cysts in early stages, hydatidosis could be
      misdiagnosed in this sample. It is concluded that serologic tests should be
      performed to all cystic hepatic ultrasonographic lesions, specially in zones with
      high infestations rates.

PMID- 7809521
TI  - [Hyperinsulinemia in thyrotoxic hypokalemic periodic paralysis: 2 clinical
      cases].
AB  - Thyrotoxic hypokalemic periodic paralysis is infrequent in white populations and
      its physiopathology is not well known. We report two white male patients (aged 25
      and 29 years old) in whom hyperinsulinemia was documented during an episode of
      hypokalemic paralysis.

PMID- 7809522
TI  - [Laparoscopic lumboaortic retroperitoneal lymphadenectomy in testicular
      neoplasm].
AB  - Lumboaortic lymphadenectomy is a therapeutic alternative for patients with
      nonseminomatous testis tumors and its principal untoward effect is the loss of
      ejaculation. The anatomic knowledge of lymph node metastasis allows lower limit
      definition of aortic dissection, maintaining the diagnostic sensitivity and
      ejaculation. We report three patients with nonseminomatous testis tumors
      subjected to a reduced video-laparoscopic lumboaortic lymphadenectomy. An
      adequate amount of tissue was obtained in all and lymph node metastasis found in
      two. No complications occurred and patients were discharged 48 hours later. It is
      concluded that this technique is an alternative staging technique with low
      morbidity that allows a rapid patient discharge.

PMID- 7809523
TI  - [A case of congenital chagasic megaesophagus: evolution until death caused by
      esophageal neoplasm, at 27 years of age].
AB  - A symptomatic megaesophagus was demonstrated in a three months old boy with
      Chagas disease. He had a difficult evolution with frequent aspiration pneumonias
      and progressive undernutrition. At 14 years old a cardiomyotomy (Heller's
      procedure) was performed, with good results that allowed a near normal life. At
      27 years old, the patient started with progressive dysphagia due to an epidermoid
      esophageal carcinoma and died after surgery. Since a higher frequency of
      esophageal carcinoma is observed in achalasia, periodic endoscopic examinations
      are mandatory.

PMID- 7809524
TI  - [Quality standards for medical schools].

PMID- 7809525
TI  - [New medical schools in Chile].
AB  - In Chile there are six established medical schools at public (Chile, Valparaiso
      and Temuco) or private (Catholic, Concepcion and Austral) universities created
      between 1833 and 1971. Since 1990, three new medical schools (two private) were
      created and a fourth is projected, concerning the chilean medical corps. We
      present three position articles on the subject written by Dean Pedro Rosso, from
      the Catholic University, Dr Pedro Castillo, Chief of Human Resources of the
      Ministry of Health and Dean Alejandro Goic from the University of Chile. Dean
      Rosso emphasizes the need to have assessment procedures that guarantee quality
      standards in the new medical schools. Dr Castillo attracts attention on
      preserving the compromise with the society, inherent to chilean medicine. Dean
      Goic analyzes systematically the reasons to prevent the proliferation of medical
      schools in the country, maintaining an equilibrium between freedom of teaching
      and public faith protection.

PMID- 7809526
TI  - [Establishing new medical schools in Chile].
AB  - In Chile there are six established medical schools at public (Chile. Valparaiso
      and Temuco) or private (Catholic. Concepcion and Austral) universities created
      between 1833 and 1971. Since 1990, three new medical schools (two private) were
      created and a fourth is projected, concerning the chilean medical corps. We
      present three position articles on the subject written by Dean Pedro Rosso, from
      the Catholic University, Dr Pedro Castillo, Chief of Human Resources of the
      Ministry of Health and Dean Alejandro Goic from the University of Chile. Dean
      Rosso emphasizes the need to have assessment procedures that guarantee quality
      standards in the new medical schools. Dr Castillo attracts attention on
      preserving the compromise with the society, inherent to chilean medicine. Dean
      Goic analyzes systematically the reasons to prevent the proliferation of medical
      schools in the country, maintaining an equilibrium between freedom of teaching
      and public faith protection.

PMID- 7809527
TI  - [Regression of left ventricular hypertrophy in essential arterial hypertension].
AB  - The classic concept of a direct pathogenic relationship between high blood
      pressure and development of left ventricular hypertrophy has been challenged by
      observations such as the modest correlations between blood pressure and magnitude
      of left ventricular hypertrophy, its frequent reversal with some antihypertensive
      medications and its experimental prevention with low doses of an angiotensin
      converting enzyme inhibitor that do not modify blood pressure. This evidence has
      prompted the revision of mechanisms or factors involved in the development of
      left ventricular hypertrophy. The roles of sympathetic nervous and renin
      angiotensin systems, genetic and endothelial factors, are reviewed in this
      article. It is concluded that blood pressure is not the sole responsible for left
      ventricular hypertrophy, but an epiphenomenon of one or more local or tissular
      mechanisms, primary or unchained by an unknown genetic factor.

PMID- 7809528
TI  - [Whooping cough epidemiology in Chile (1950-1990). The adult as new reservoir of
      infection?].
AB  - The epidemiology of whooping cough is analyzed using the disease notifications in
      Metropolitan Region and some rural areas from 1950 to 1990. Morbidity rate
      tendencies show a decreasing endemic disease interrupted by irregular increases,
      the last in 1985. Mortality fell from 11.9 per 100,000 in 1950 (60% of deaths in
      boys of less than one year old), to less than 1 per 100,000 since 1967. Since
      1982, all deaths occurred in less than one year old boys. Lethality was high
      initially, specially in rural areas but the differences with Metropolitan area
      decreased since 1975. Approximately 90% of notifications are in less than one
      year old boys. However, there is a sustained rate elevation in boys older than 10
      years old, predicting the increasing importance of the infection in young adults.
      The described changes antedate and are intensified by the immunization program.
      Their relationship to the lack of compliance with the program and the vaccine
      efficacy are discussed.

PMID- 7809529
TI  - [Ideas contributing to the reform of the health sector in Chile].
AB  - General criteria are proposed for the organization of chilean health system. The
      fundamental ideas emphasize administrative decentralization, an effective and
      expedite intercommunication between different attention levels and a
      rationalization of the use of diagnostic procedures and treatments. The "basic
      health plan" features are outlined. The need for patient and family education and
      the access to tertiary medicine only through referrals is highlighted. The second
      part of article proposes changes in Medical Education. The need to reorient
      undergraduate medical formation towards solving outpatient problems and to extend
      specialization possibilities to all graduates, including Adult and Children
      general medicine training programs, is emphasized. The incorporation of basic
      economical concepts to the curriculum and group work training is considered
      beneficial. Finally, self-teaching behaviors and resolutive capacities in legal
      and ethical aspects should be encouraged in students. The potential teaching
      roles of future health reference, diagnostic and therapeutic centers is
      insinuated.

PMID- 7809530
TI  - [Effects of neomycin on intestinal digestion, absorption and fermentation of
      carbohydrates in patients with liver cirrhosis: evidence for an alternative
      therapeutic mechanism in hepatic encephalopathy].
AB  - BACKGROUND: Despite non absorbable antibiotics and neomycin may have antagonistic
      effects on intestinal bacterial environment, both have synergistic effects in the
      treatment of hepatic encephalopathy. This could be due to their action on
      different enteric flora or a neomycin induced carbohydrate malabsorption. AIM: To
      investigate the effects of neomycin on intestinal digestion, absorption and
      fermentation of carbohydrates in patients with liver cirrhosis. PATIENTS AND
      METHODS: Thirty eight Child B or C cirrhotic patients separated in three groups;
      subjects within each group were randomized to receive neomycin (2/g/day for 10
      days, n = 8) or placebo (n = 4). Absorption of lactose and d-xylose and
      fermentation of d-xylose, lactose and lactulose (measured using hydrogen breath
      tests) were studied before and after the treatment period. RESULTS: Neomycin did
      not change lactose fermentation but reduced plasma glucose rise after lactose
      ingestion (38.8 +/- mg/dl to 22 +/- 6 mg/dl p < 0.05). Plasma d-xylose levels at
      30 min and its 5 h urinary excretion were reduced by neomycin from 19 +/- 3 to 9
      +/- 2 mg/dl and from 4.9 +/- 0, 8 to 2.6 +/- 0.3 g/5h respectively (p < 0.05).
      Fermentation of d-xylose, lactose and lactulose was not reduced by neomycin. No
      significant changes were observed after placebo treatment. CONCLUSIONS: Neomycin
      therapy is associated with a reduction of intestinal digestion and absorption of
      carbohydrates, preserving bacterial fermentation capacity, probably increasing
      the non absorbable carbohydrate load reaching the colon.

PMID- 7809531
TI  - [Frequency of lumbar spine osteopenia in an asymptomatic postmenopausal Chilean
      population].
AB  - The aim of this study was to assess lumbar spine bone density in a group of
      chilean postmenopausal females and to estimate the frequency of vertebral
      osteopenia in the national urban female population. A clinical assessment and
      lumbar spine bone density measurement were performed to 171 healthy women over 40
      years of age and not receiving medications that modify bone turnover. Calcium
      ingestion was recalled in 77 of these. Fifty women (29.2%) had osteopenia,
      defined as a bone density of less than 0.92 g/cm2. Extrapolating this figure to
      the national urban population, an osteopenia frequency of 21.7% was estimated.
      Body mass index was 25.5 +/- 3.8 and 57% of the sample was overweight. Calcium
      ingestion was 740.3 +/- 331.7. These two parameters did not correlative with bone
      density. Women with osteopenia were older and had a longer postmenopausal lapse
      than those with normal bone density. The completion of further clinical an
      epidemiological studies is recommended to know the real magnitude of osteoporosis
      in Chile.

PMID- 7809532
TI  - [Magnitude and declared causes of absenteeism for health reasons among faculty
      and students of a medical school].
AB  - All sick leaves during 1989 among academics and students of a Faculty of Medicine
      were analyzed. Twenty three percent of academics and 60.5% of students had at
      least one sick leave during the year. The mean general rate of absenteeism among
      academics was 3.55% (1.6% among men and 8.09% among women). The mean length of
      sick leaves was 13.5 days. Eighteen percent of lost working days were due to
      pregnancy, lactation or care needs of less than one year children. Tumors,
      trauma, respiratory, digestive and mental illnesses accounted for 72.8% of lost
      working days. Medical students had a mean general absenteeism rate of 2.66%
      (ranging between 1.8% among male sixth year and 4.8% among female fourth year
      students). Mean length of sick leaves was 3.5 days (ranging from 2.98 among
      female fifth year and 6.7 among male sixth year students). Respiratory, digestive
      and infectious diseases accounted for 74% of lost days. No sick leaves were
      observed, due to pregnancy or lactation among students or due to occupational
      diseases among academics.

PMID- 7809534
TI  - [Primary coronary angioplasty as early reperfusion treatment of acute myocardial
      infarction].
AB  - Between March 1990 and July 1993, 21 patients with an evolving acute myocardial
      infarction were treated with coronary angioplasty after 2-9 hours of chest pain
      (mean 3.9). Thirteen had a clinically and electrocardiographically large
      infarction, including 3 in cardiogenic shock. The dilated arteries were the left
      anterior descending in 14, the left circumflex in 4 and right coronary artery in
      3 patients. With angioplasty successful reperfusion of the infarct area was
      obtained in 18 patients (86%). The procedure was well tolerated by most patients
      and the in-hospital mortality rate was 5%.

PMID- 7809533
TI  - [Continuous hemodialysis with cuprophan membranes in critical patients].
AB  - The aim of this work was to evaluate the use of 1 m2 Cuprophan hollow fiber
      filters for continuous arteriovenous hemodialysis procedures. Thirty one
      critically ill patients (18 male) aged between 20 and 80 years old, subjected to
      35 hemodialysis procedures were studied. Sixteen patients had acute renal failure
      (10 of these had multiorgan failures) and 15 terminal chronic renal failure.
      Femoral vessels were used for vascular access and isotonic peritoneal dialysis
      solution flowing at 16.6 ml/seg as dialyzing solution. No extracorporeal pump
      assistance was used. Mean procedure time was 76 +/- 69.7 h, filter consumption
      was 2.8 +/- 2.1 filters/procedure, ultrafiltration rate was 168 ml/min and urea
      clearance was 19.9 +/- 4.4 ml/min. No replacement solutions were required and
      good electrolyte and circulating volume control was achieved with excellent
      hemodynamic stability. Blood urea fell from 116.9 +/- 49.1 to 64 +/- 27.2 mg/dl
      after the procedure (p < 0.001). Hyperglycemia was observed in eight procedures,
      six patients developed non infectious vascular access complications and two
      patients catheter related sepsis. We conclude that continuous arteriovenous
      hemodialysis using cuprophan membranes is a good renal substitution technique for
      critically ill patients.

PMID- 7809535
TI  - [Gastrointestinal bleeding of unknown origin. Experience in 31 cases].
AB  - Thirty one patients with GI bleeding of obscure origin, defined as those with
      normal upper endoscopy and colonoscopy, were studied to know the yield of
      different diagnostic procedures. Seventeen patients consulted for hematochezia
      and bleeding less than 10 days of evolution in 71%. Small bowel X ray examination
      was performed in 14 cases with a diagnostic effectiveness (number of
      diagnosis/number or examination) of 14%, angiography was performed in 12 cases
      with an effectiveness 33%, radiolabeled erythrocyte scanning in 12 cases with an
      effectiveness of 75%, scintigraphy with pertechnetate in 6 cases with an
      effectiveness of 17% and intraoperatory endoscopy in 2 cases with an
      effectiveness of 50%. A definitive diagnosis was reached in 8 patients during the
      first admission and in 6 during the second admission. The principal etiologies
      were small bowel tumors in 3 cases, cecal ulcers in 2 and ileal diverticula in 2.
      Ten subjects were subjected to surgical and 2 to endoscopic treatment. Five
      patients with recurrent bleeding remain without diagnosis. It is concluded that
      radiolabeled erythrocyte scanning and angiography are effective examinations that
      should follow upper and lower endoscopies in the diagnosis of a concealed GI
      bleeding. When a diagnosis is not reached in the first admission, patients should
      be following with repeated diagnostic procedures.

PMID- 7809536
TI  - [Cholecystectomy in young women from the south-oriental area of Santiago:
      comparison between 2 periods].
AB  - The aim of this study was to know if cholecystectomy rates have decreased in
      young women, considering that these rates have decreased in the last years in the
      general chilean population. The frequency of previous cholecystectomy was
      compared in 1582 women aged 23.9 +/- 5.8 years admitted to a maternity for
      delivery between 1985 and 1986 and 4943 women aged 24.6 +/- 5.9 years admitted
      between 1989 and 1990 for the same reason. There was a reduction in
      cholecystectomy frequency from 4.7 to 2.5% specially among women 21 to 35 years
      old. Cholecystectomy was performed at a mean age of 23 years in both groups and
      42.6% of the procedures were done before the first pregnancy. An unexpected
      finding was a lower body weight among women studied in the second period (62.5 +/
      9.1 vs 67.7 +/- 8.4 k).

PMID- 7809537
TI  - [Treatment of chronic human Chagas disease with itraconazole and allopurinol.
      Preliminary report].
AB  - The aim of this work was to assess the efficacy of itraconazole and allopurinol
      in chronic Chagas disease. Two hundred two subjects (137 infected, 59 with Chagas
      cardiopathy and 6 with non chagasic cardiopathy) were randomly assigned to be
      treated with itraconazole (87 subjects receiving 6 mg/kg/day for 120 days),
      allopurinol (68 subjects receiving 8.5 mg/kg/day for 60 days) or placebo (47
      subjects during 60 days). Medications were well tolerated. Indirect
      hemagglutination test was modified in 5 subjects (3.2%) after treatment.
      Initially positive xenodiagnosis became negative in 34 of 36 subjects (94.4%)
      treated with itraconazole and 8 of 10 subjects (80%) treated with allopurinol.
      Initially normal EKG was not modified in 100% of patients receiving placebo,
      84.9% receiving itraconazole and 86.7% receiving allopurinol. Initially abnormal
      EKG became normal in 10 of 31 subjects (32%) receiving itraconazole, 8 of 20
      (40%) receiving allopurinol and none of 8 receiving placebo. It is concluded that
      xenodiagnosis and EKG improvements indicate that itraconazole and allopurinol
      have a role in the treatment of chronic Chagas disease. A 36 months follow up of
      these patients will help to confirm this conclusion.

PMID- 7809538
TI  - [Multiple pathway tachycardias: electrophysiological properties and fulguration
      of accessory pathways in 2 cases].
AB  - We report two patients (male, 35 and female, 28 years old) with recurrent and
      refractory tachycardias referred for an electrophysiological study. EKG showed
      left lateral accessory pathway in both, two tachycardias with identical
      morphology but with different frequency and activation sequence were detected.
      One was orthodromic with anterograde conduction by the His-Purkinje budle and
      retrograde by the accessory pathway and the other with slow nodal anterograde
      conduction. The accessory pathway was first fulgurated with radiofrequency at the
      third attempt. Posteriorly, a nodal reentry tachycardia was induced in the first
      patient and in the second, a double nodal pathway was confirmed. In both, the
      slow pathway was modified using Jackman's technique, after three and four
      attempts respectively. After these applications, the induction of tachycardia
      with programmed atrial or ventricular stimulation, with or without isoproterenol,
      was not possible. It is concluded that radiofrequency fulguration is a reasonable
      therapeutic alternative for patients with multiple circuit tachycardias.

PMID- 7809539
TI  - [Tomographic myocardial perfusion (SPECT) using 99mTc sestamibi-dipyridamole and
      2-d-echocardiography with amrinone pre and post myocardial revascularization in 2
      cases].
AB  - We report two male patients aged 50 and 55 years old with coronary artery disease
      who were treated with surgical revascularization and angioplasty respectively. To
      assess viable and ischemic myocardial territories, they were studied before and
      after revascularization with radionuclide perfusion SPECT with Tc99m-Sestamibi
      under Dipyridamole and with 2-D echocardiography at baseline and after the use of
      amrinone. Improvement in relative perfusion on SPECT and wall motion on 2-D
      echocardiography indicated tissue recovery.

PMID- 7809540
TI  - [Effect of chronic blockade of the opiodergic receptor on insulin resistance in a
      hyperandrogenic woman].
AB  - We report a woman with insulin resistance associated with hyperandrogenism and
      acanthosis nigricans (HAIR-AN syndrome) treated during 30 days with the prolonged
      action opioid antagonist Naltrexone. During its administration, decreases in
      basal blood glucose and serum insulin, insulin and glucose response to a glucose
      load and plasma testosterone were observed. These findings suggest that opioid
      activity could play a critical role in the physiopathology of hyperinsulinemia in
      hyperandrogenic women.

PMID- 7809542
TI  - [Early abortion: natural failure or lack of a critical spirit?].
AB  - The existence of spontaneous, clinically inapparent early abortions seems to be
      generally acknowledged in the scientific literature. The lack of scientific
      criticism about the limitations and inconsistencies on the quantitative
      estimation of these early losses is however striking. This study examines
      critically the published primary scientific evidence about early spontaneous
      clinically inapparent abortions. Three main methods are disclosed: 1) Direct
      inspection of the uterus and fallopian tubes; 2) Theoretical assumptions, and, 3)
      Estimates of 'biochemical abortions'. Estimates ranging from 7.6% to 56.8% of all
      pregnancies are obtained by experimental studies. Actual methodological
      shortcomings and inter-group variability in results provide no scientific ground
      for a quantitative agreement. The results of this study preclude the utilization
      of a precise quantitative estimate of early spontaneous clinically inapparent
      abortions in any rational discussion, unless new experimental evidence could be
      provided.

PMID- 7809544
TI  - [How can we help our patients to stop smoking?].
AB  - Anti-smoking counseling by physicians has demonstrated to be the treatment
      modality of smokers with the best cost-benefit ratio. The basic stages of
      physician intervention are summarized in the four "A's" of clinical activities:
      ask, advise, assist, arrange. The systematic use of this methodology by the
      health teams could achieve 80000 ex-smokers per year in our country.

PMID- 7809541
TI  - [Polyneuropathies and dysglobulinemias].
AB  - We review the concept fo Monoclonal Gammopathy emphasizing that the so called
      benign forms, with or without polyneuropathy can have an unpredictable evolution.
      Polyneuropathies associated to monoclonal gammopathy-IgM, IgG, IgA, Waldestrom's
      disease, Multiple myeloma, Osteosclerotic myeloma (POEMS), Amyloidosis and
      Cryoglobulinemias are reviewed. They generally are solely sensory, sensorimotor
      or rarely, solely motor. The importance of neuro-physiological studies and nerve
      biopsy is emphasized. For progressive forms, treatment with plasmapheresis,
      immunotherapy, corticoids or intravenous gammaglobulin is suggested.

PMID- 7809543
TI  - [Dietary ingestion of fluoride and caries prevalence in preschool and school
      children in cities with different fluoride content in the drinking water and
      diet].
AB  - The consumption of dietary fluoride and its relationship with dental caries
      prevalence was determined in 780 preschool children and 802 school children from
      quique, Arica, Santiago and San Antonio, where drinking water has different
      fluoride concentration. Dietary fluoride was determined from dietary records and
      fluoride content of foods. The fluoride consumption from drinking water was
      calculated by Galagan and Vermillion formula. The total fluoride consumption was
      obtained. The dental caries prevalence was established by the evaluation of
      dental caries index in deciduous (dmft) and permanent (DMFT) dentition.
      Significantly lower DMFT values were founded in cities with lower fluoride levels
      in drinking water. The exception was San Antonio, where high dietary fluoride
      explained the lower DMFT values relative to Santiago. Our results suggest that
      not only fluoride in water but also the consumption of fluoride rich foods has a
      significant impact on the prevalence of caries.

PMID- 7809545
TI  - [Surgery for leg fractures. Anesthesia].

PMID- 7809546
TI  - [Treatment of leg fractures].

PMID- 7809548
TI  - [Rehabilitation of leg fractures].

PMID- 7809547
TI  - [Nursing care of leg fractures].

PMID- 7809549
TI  - [The nurse and pain].

PMID- 7809550
TI  - [Leg fractures. Anatomy and physiology].

PMID- 7809551
TI  - [Diagnosis of a leg fracture].

PMID- 7809552
TI  - Exercise dependence syndrome in runners.

PMID- 7809553
TI  - Effect of surgical timing on return to sports activity after significant knee
      injuries.

PMID- 7809554
TI  - Exercise-induced asthma and anaphylaxis.
AB  - With increased popularity in exercise, the number of individuals with exercise
      induced asthma (EIA), or 'exercise-induced bronchospasm', has increased due to an
      increased awareness among physicians of the clinical symptoms associated with
      EIA. EIA affects approximately 75 to 95% of asthmatic patients. 40% of children
      with allergic rhinitis have EIA, whereas only 3 to 11% of nonasthmatics have EIA.
      Although athletes with asthma have been recognised for years, EIA in nonasthmatic
      individuals has gained recognition since the 1984 Olympics. Vague symptoms of
      recurring poor performance, fatigue despite adequate conditioning, or 'getting
      winded' during an athlete's usual workout may be the presenting complaints.
      Athletes may be more likely to attribute these symptoms to poor conditioning or
      an upper respiratory infection, and not seek immediate assistance. Younger
      athletes may complain of stomach ache or refuse to participate in strenuous play
      because of an inability to keep up with other children. Additionally, an
      awareness of exercise-induced anaphylaxis needs to be considered when discussing
      aspects of airway compromise following exercise; however, its presentation is
      more urgent than those with EIA. Although the pathophysiology of EIA is somewhat
      controversial, the most likely explanation is a combination of heat and water
      loss leading to mediator release. The different medications that have been used
      to treat EIA are based on theories regarding the bronchial hyperreactivity of
      EIA.

PMID- 7809557
TI  - [Bridge between scientific medicine and complementary medicine--utopia?].
AB  - In this keynote presentation on a complex and controversial subject, I attempt to
      answer the following questions: 1. What is scientific medicine, what is
      alternative medicine? 2. Why is there in our days an increasing trend in the
      population towards concepts and methods of alternative (complementary) medicine?
      3. Why are many scientific physicians defensive, sceptical and opposed to
      alternative medicine? 4. Are traditional and alternative medicine fundamentally
      irreconcilable worlds? The author believes that complementary medicine is
      beneficial and justified especially in private practice, above all in the many
      patients suffering from psychosomatic, psychovegetative, neurotic, depressive,
      functional disorders, with feelings of ill-health and often with marked
      subjective symptoms but in which no severe organic disease is present. In these
      types of patients alternative methods are often 'more gentle' and cost-effective.
      The doctor's personality, his empathy, his willingness to communicate are
      decisive factors for their effectiveness. Certain methods of complementary
      medicine should be increasingly integrated into our hospitals and be learnt and
      critically assessed locally by the scientific physicians. Scientific medicine is
      and remains the indispensable solid foundation for correctly indicating the use
      of alternative therapeutic methods.

PMID- 7809556
TI  - Exercise, training and injuries.
AB  - Although exercise results in a number of well documented physical fitness and
      health benefits, accruing such benefits entails a risk of exercise-related
      injuries. Musculoskeletal injuries occur frequently among fitness programme
      participants, runners, athletes, military recruits and others who engage in
      routine vigorous exercise. The same parameters of exercise (intensity, duration
      and frequency) that determine the positive fitness and health effects of physical
      training also appear to influence the risk of injuries. Studies of runners and
      other physically active groups have consistently demonstrated that greater
      duration and frequency of exercise are associated with higher risks of injury.
      However, the sports medicine literature shows little association between exercise
      intensity and injuries, a finding which may be misleading. The strongest and most
      consistent association reported exists between greater total amounts of exercise
      and higher risks of injury. This is not surprising, since the total amount of
      exercise is the product of the intensity, duration and frequency of exercise.
      Recent military research confirms the finding that higher volumes of running are
      associated with higher rates of injury. Furthermore, the study of army recruits
      suggests that greater amounts of exercise not only result in greater risks of
      injury, but in some instances may also impart no additional increase in fitness,
      a finding consistent with an earlier study of civilian runners. Several military
      studies also demonstrate that those recruits who have been more physically active
      in the past are less likely to be injured during basic training. These military
      studies also document a number of other factors, such as older age, smoking,
      sedentary jobs and lifestyle, high or low flexibility and high arches of the
      feet, which may contribute to or modify the risks for exercise-related injuries.
      In conclusion, the present review suggest that, for activities such as running,
      specific parameters of exercise may contribute to the overall risk of injuries in
      rough proportion to their contribution to the total amount of activity performed.
      Also, better knowledge of the effects of the parameters of training and other
      factors on the risks of exercise-related injuries is necessary to make more
      judicious choices about how to best achieve the benefits of exercise and to
      prevent injuries.

PMID- 7809558
TI  - [Academic medicine and complementary medicine differ from each other in reasoning
      and evaluation but not in goals].
AB  - The principal objective of all medical activity is to prevent deterioration of
      health, but also its recuperation, when it has been lost, by mobilisation of
      inner, natural resources and the commitment of practical knowledge about ill
      health. This is less true not for individuals with regard to their proper care,
      than for practitioners of the arts and sciences of healing towards those who seek
      their help, regardless of the 'school' to which they may belong. If such
      objectives are generally accepted, the way to their accomplishment is open.
      However relevant and justifiable differing intentions may be, they become
      difficult to materialize if energy is squandered in futile disputes over
      territorial rights. It is the purpose of the Swiss National Science Foundation's
      'Komplementarmedizin' Programme (NFP 34) to build bridges between different
      territories. (See the Table of Projects currently being undertaken at the end of
      this article.)

PMID- 7809559
TI  - [Is homeopathy accessible to research?].
AB  - This paper critically examines the scientific status of homeopathy. Against the
      background of latest research and the theoretical presuppositions of homeopathy,
      it is discussed, whether and how, homeopathy is amenable to scientific research.
      At the outset, the principal notions of homeopathy: similarity, potentiation and
      understanding of chronic diseases, are explained. Then the question is posed
      whether in recent research these notions have found adequate expression in
      research protocols, design and measured parameters. Although there is quite a
      bulk of literature now, only few publications address the principal notions of
      homeopathy adequately. It can be concluded, therefore, that homeopathy has not,
      as yet, been properly investigated. The question is addressed, how the
      homeopathic notion of the individual remedy should be put into practice in
      clinical trials, and what kind of clinical trials are possible in homeopathy. The
      necessity for placebo-controlled, randomized trials is discussed and a
      modification of the classical design for long term studies is introduced. Other
      research options are also shown. Finally, theoretical models for the explanation
      of possible high-dilution effects are shortly introduced and examined. It is
      argued that homeopathy is amenable to scientific research, and the terms of such
      research are made explicit.

PMID- 7809560
TI  - [Health--disease: theory and practice of "integrative medicine"].
AB  - Worldwide our knowledge about health and disease and the frame as well as the
      goals in our medical education are increasingly discussed by the medical
      profession and our society. Therefore some aspects are presented in order to
      develop perspectives for and in our thinking and actions in an 'integrative
      medicine'. The five entities, formulated, through Paracelsus about 500 years ago,
      are transformed into our time. Regardless of necessary technical advances in
      medicine, it becomes increasingly obvious that we still have to integrate the
      different entities of Paracelsus into a multilayered composite medicine in the
      coming decades.

PMID- 7809561
TI  - A longitudinal study of laboratory- and diary-based sleep measures in healthy
      "old old" and "young old" volunteers.
AB  - The major aim of this study was to examine laboratory- and diary-based measures
      of sleep in a group of healthy ("successfully aging") "old old" subjects (> or =
      75 years of age), as contrasted with a group of "young old" subjects (60-74 years
      of age), who were followed longitudinally for 2 years. We hypothesized that sleep
      would deteriorate to a greater extent over time among the old old subjects than
      among the young old. The study group consisted of 50 elders (21 male, 29 female;
      23 old old, 27 young old), each studied at baseline and then again at 1- and 2
      year follow-up. Analysis of variance was used to determine main effects of age
      group, gender and time on key sleep measures. Most measures were found to be
      remarkably stable over time. However, some decay was detected in sleep efficiency
      among the old old, but not among the young old. In a multiple regression model
      for the cohort as a whole, age, cognitive status and medical burden at baseline
      predicted subsequent declines in sleep efficiency over the 2-year period. To our
      knowledge, this is the first longitudinal data set on sleep in the healthy old
      old.

PMID- 7809562
TI  - The thermoregulatory effects of menopausal hot flashes on sleep.
AB  - Menopausal hot flashes are thought to be a disorder of thermoregulation initiated
      centrally within the medial preoptic area of the hypothalamus. These heat-loss
      mechanisms appear to be activated in the presence of normal core body
      temperature. Previous studies have demonstrated that thermal stimuli have the
      potential to alter sleep stages. We performed 24-hour ambulatory recordings of
      hot flashes and all-night sleep parameters on 12 postmenopausal women with hot
      flashes and seven postmenopausal women without flashes to determine whether the
      presence of hot flashes prior to sleep or during sleep itself would result in
      alterations in sleep pattern. The results show that hot flashes are associated
      with increased Stage 4 sleep and a shortened first rapid eye movement period. Hot
      flashes occurring in the 2 hours prior to sleep onset were positively correlated
      with the amount of slow-wave sleep. The central thermoregulatory mechanism
      underlying hot flashes may affect hypnogenic pathways inducing sleep and heat
      loss in the absence of a thermal load.

PMID- 7809563
TI  - Sleep onset is associated with retrograde and anterograde amnesia.
AB  - The purpose of the present study was to examine explicit and implicit memory for
      auditory events presented immediately prior to sleep onset. The results of the
      present study suggest subjects allowed 10 minutes of sleep demonstrate deficient
      explicit memory for auditory stimuli presented immediately prior to sleep onset.
      Subjects showed severe free recall deficits for word pairs presented 3 minutes
      prior to sleep onset and recognition deficits for stimuli from 1 minute prior to
      sleep onset. Implicit memory for word pairs presented prior to sleep onset seemed
      intact, and no recency effect was observed. In contrast to the 10-minute
      condition, subjects allowed 30 seconds of sleep demonstrated no equivalent
      explicit memory deficits. Memory performance in both delay conditions, however,
      appeared globally impaired relative to control data from subjects who remained
      awake. The results are interpreted in terms of elaboration of stimulus encoding,
      interruption of consolidation and retrograde versus anterograde amnesia.

PMID- 7809555
TI  - Achilles tendon injuries in athletes.
AB  - Two-thirds of Achilles tendon injuries in competitive athletes are paratenonitis
      and one-fifth are insertional complaints (bursitis and insertion tendinitis). The
      remaining afflictions consist of pain syndromes of the myotendineal junction and
      tendinopathies. The majority of Achilles tendon injuries from sport occur in
      males, mainly because of their higher rates of participation in sport, but also
      with tendinopathies a gender difference is probably indicated. Athletes in
      running sports have a high incidence of Achilles tendon overuse injuries. About
      75% of total and the majority of partial tendon ruptures are related to sports
      activities usually involving abrupt repetitive jumping and sprinting movements.
      Mechanical factors and a sedentary lifestyle play a role in the pathology of
      these injuries. Achilles tendon overuse injuries occur at a higher rate in older
      athletes than most other typical overuse injuries. Recreational athletes with a
      complete Achilles tendon rupture are about 15 years younger than those with other
      spontaneous tendon ruptures. Following surgery, about 70 to 90% of athletes have
      a successful comeback after Achilles tendon injury. Surgery is required in about
      25% of athletes with Achilles tendon overuse injuries and the frequency of
      surgery increases with patient age and duration of symptoms as well as occurrence
      of tendinopathic changes. However, about 20% of injured athletes require a re
      operation for Achilles tendon overuse injuries, and about 3 to 5% are compelled
      to abandon their sports career because of these injuries. Myotendineal junction
      pain should be treated conservatively. Partial Achilles tendon ruptures are
      primarily treated conservatively, although the best treatment method of chronic
      partial rupture seems to be surgery. Complete Achilles tendon ruptures of
      athletes are treated surgically, because this increases the likelihood of
      athletes reaching preinjury activity levels and minimises the risk of re
      ruptures. Marked forefoot varus is found in athletes with Achilles tendon overuse
      injuries, reflecting the predisposing role of ankle joint overpronation. Athletes
      with the major stress in lower extremities have often a limited range of motion
      in the passive dorsiflexion of the ankle joint and total subtalar joint mobility,
      which seems to be predisposing factor for these injuries. Various predisposing
      transient factors are found in about one-third of athletes with Achilles tendon
      overuse injuries; of these, traumatic factors (mostly minor injuries)
      predominate. The typical histological features of chronically inflamed
      paratendineal tissue of the Achilles tendon are profound proliferation of loose,
      immature connective tissue and marked obliterative and degenerative alterations
      in the blood vessels. These changes cause continuing leakage of plasma proteins,
      which may have an important role in the pathophysiology of these injuries. The
      chronically inflamed paratendineal tissues of the Achilles tendon do not seem to
      have enough capacity to form mature connective tissue.

PMID- 7809564
TI  - Long-term compliance to continuous positive airway pressure therapy (nCPAP) set
      up during a split-night polysomnography.
AB  - We studied prospectively the acute and long-term compliance with nasal continuous
      positive airway pressure (nCPAP) therapy set up during a split-night
      polysomnography in 31 patients suffering from severe obstructive sleep apnea
      syndrome (OSAS). The mean apnea-hypopnea index (AHI) was 66 +/- 23/hour. An
      effective nCPAP (AHI < 10/hour in all sleep stages in the dorsal decubitus) was
      titrated in 27/31 patients. The mean effective nCPAP was 11 +/- 2 cm H2O. In
      three patients, a subsequent night was necessary to determine the effective nCPAP
      during rapid eye movement sleep, and one patient did not support the treatment.
      Of the 27 patients with successful titration, 21 accepted home treatment, three
      chose a surgical procedure and three refused to be treated. Of the 21 accepting
      home treatment, one patient did not receive his insurance agreement and could not
      participate in follow-up. Among the 20 other patients, four interrupted their
      treatment during the 1st month because of discomfort, and 16 were followed for
      285 +/- 84 days. The daily rate of nCPAP use for the compliant patients was 6.7
      +/- 1.5 hours. These preliminary results indicate that a split-night technique is
      reliable and cost saving in a majority of patients suffering from severe OSAS.

PMID- 7809565
TI  - Snoring: is it in the ear of the beholder?
AB  - Complaint of snoring, which is usually voiced by a patient's bedpartner,
      frequently leads to investigations in the sleep laboratory that are designed to
      assess snoring objectively and determine whether it is a symptom of sleep apnea.
      How well this subjective complaint of the listener is confirmed by the objective
      measurement of snoring is not known. Consequently, we designed a study i) to test
      the validity of self-perception of snoring and ii) to compare subjective
      perception of snoring by the sleep technologist with objective measurement of its
      frequency and loudness. We studied 613 unselected patients referred to our sleep
      clinic because of snoring and suspicion of sleep apnea. They all had nocturnal
      polysomnography that included measurements of snoring, expressed as the number of
      snores per hour of sleep [snoring index (SI)] and mean (dBmean) and maximum
      (dBmax) nocturnal sound intensity. Following the sleep study, the technologist
      (and patient) independently rated a patient's snoring as none, mild, moderate or
      severe. Kruskall-Wallis test, Spearman rank correlations and Cohen's kappa
      statistics were used to compare the groups, examine the correlations between
      subjective and objective measurements, and check the agreement between
      them.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7809566
TI  - Ventilatory instability in patients with congestive heart failure and nocturnal
      Cheyne-Stokes breathing.
AB  - Many of the factors that appear to cause Cheyne-Stokes Breathing (CSB) in
      sleeping patients with congestive heart failure (CHF) are present during
      wakefulness. We studied the stability of ventilatory pattern in nine awake CHF
      patients (left ventricular ejection fraction 9-48%) who demonstrated CSB only
      while asleep and compared results with 13 age-matched normals. The test involved
      brief (30-50-second) exposure to hypoxia (end-tidal PO2 = 55 Torr) followed by
      breathing pure oxygen. During hypoxia, ventilation increased about 40% above air
      breathing control in both groups, whereas end-tidal CO2 declined to 92% of
      control in both groups. During hyperoxia, however, breathing pattern differed
      between groups. In the normals, ventilation gradually declined to air-breathing
      levels and did not significantly undershoot. In the patients, ventilation dropped
      more rapidly to baseline and an overshoot was present with ventilation being 72%
      and air-breathing control at 45 seconds of hyperoxia. Circulatory delay was
      calculated from the time interval between alveolar hypoxia and in increase in
      ventilation, and when corrections for circulatory delay were applied to
      ventilation during hyperoxia the differences between groups increased in that the
      patients' ventilation was less than baseline immediately after the delay. In the
      normals, the gradual decline in hyperoxic ventilation probably represents the
      decay of short-term potentiation (STP) activated by hypoxic hyperventilation.
      Results in the patients were compatible with absence of such STP decay, but could
      also have been due to a reduction in ventilatory drive early in hyperoxia related
      to prolonged circulation times.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7809567
TI  - Dark goggles and bright light improve circadian rhythm adaptation to night-shift
      work.
AB  - We compared the contributions of bright light during the night shift and dark
      goggles during daylight for phase shifting the circadian rhythm of temperature to
      realign with a 12-hour shift of sleep. After 10 baseline days there were 8 night
      work/day-sleep days. Temperature was continuously recorded from 50 subjects.
      There were four groups in a 2 x 2 design: light (bright, dim), goggles (yes, no).
      Subjects were exposed to bright light (about 5,000 lux) for 6 hours on the first
      2 night shifts. Dim light was < 500 lux. Both bright light and goggles were
      significant factors for producing circadian rhythm phase shifts. The combination
      of bright light plus goggles was the most effective, whereas the combination of
      dim light and no goggles was the least effective. The temperature rhythm either
      phase advanced or phase delayed when it aligned with daytime sleep. However, when
      subjects did not have goggles only phase advances occurred. Goggles were
      necessary for producing phase delays. The most likely explanation is that
      daylight during the travel-home window after a night shift inhibits phase-delay
      shifts, and goggles can prevent this inhibition. Larger temperature-rhythm phase
      shifts were associated with better subjective daytime sleep, less subjective
      fatigue and better mood.

PMID- 7809568
TI  - The acute effects of nefazodone, trazodone and buspirone on sleep and sleep
      related penile tumescence in normal subjects.
AB  - This study examined the effects of nefazodone, trazodone and buspirone on sleep
      and sleep-related penile tumescence. Trazodone is a sedating antidepressant
      without anticholinergic properties. Nefazodone is a new antidepressant that is a
      structural analogue of trazodone but is less sedating. Buspirone is a
      nonsedating, nonbenzodiazepine anxiolytic with antidepressant properties.
      Nefazodone was compared to trazodone and buspirone in a double-blind, placebo
      controlled crossover study in 12 normal healthy males. Nefazodone increased rapid
      eye movement (REM) sleep, whereas trazodone and buspirone suppressed REM sleep.
      The drugs only minimally affected other sleep stages. Trazodone increased total
      tumescence time by delaying the onset of detumescence; nefazodone increased total
      tumescence time only insofar as it increased REM sleep; buspirone did not change
      total tumescence time when compared to placebo. The results support a growing
      body of data indicating that not all antidepressants suppress REM sleep. The
      results also are consistent with the interpretation of an earlier study showing
      that trazodone prolongs penile tumescence during sleep as a result of its alpha
      adrenergic blocking properties that suppress detumescence. Nefazodone, with less
      alpha-adrenergic blocking activity, did not abnormally penile tumescence beyond
      REM sleep.

PMID- 7809569
TI  - Sleep onset insomnia, sleep maintaining insomnia and insomnia with early morning
      awakening--temporal stability of subtypes in a longitudinal study on general
      practice attenders.
AB  - The present study investigated the temporal stability of insomnia patterns during
      a 4-month study period, classifying insomnia as sleep-onset insomnia, sleep
      maintaining insomnia or insomnia with early morning awakening. In a longitudinal
      study design, 2,512 general practice attenders were investigated at the time of
      the first inquiry (T1) with a questionnaire. Four months later (T2), all patients
      complaining of difficulties in initiating and/or maintaining sleep and/or early
      morning awakening (n = 328) were again contacted by mail and received the same
      questionnaire as at T1. According to the reported symptoms, patients were
      assigned to the different subtypes of insomnia. The diagnosis at T1 was then
      compared with the diagnosis at T2 4 months later. Only about half of all patients
      who complained of difficulties in initiating sleep at T1 still exclusively
      reported sleep-onset insomnia 4 months later, whereas the remaining patients were
      distributed to different subtypes. The stability of sleep-maintaining insomnia
      and insomnia with early morning awakening was even lower. Comorbidity with a
      somatic or psychiatric disorder at T1 and change in hypnotic treatment did not
      account for the instability of the respective subgroup of insomnia. These
      findings illustrate that cross-sectional studies focusing on subtypes of
      insomnia, e.g. sleep-onset insomnia, may lead to erroneous results.

PMID- 7809570
TI  - Sleep bruxism as a manifestation of subclinical rapid eye movement sleep behavior
      disorder.
AB  - A 59-year-old man with temporomandibular joint pain/dysfunction syndrome
      presented with a long history of nocturnal bruxism. All-night polysomnographic
      recordings with video monitoring showed episodes of teeth grinding or clenching
      occurring exclusively during rapid eye movement (REM) sleep, which were often
      associated with movements of the hands and fingers and/or brief vocalization.
      Throughout REM sleep, there was excessive phasic chin electromyographic
      twitching, without increased tone, and also excessive phasic electromyographic
      twitching in multiple muscle sites. The patient maintained a normal nonrapid eye
      movement-REM cycle, but showed increased REM density. Polysomnographic
      characteristics suggested that there may be a common pathophysiology in a certain
      type of sleep bruxism and the REM sleep behavior disorder. Sleep bruxism seen in
      this case is concluded to be a manifestation of subclinical REM sleep behavior
      disorder.

PMID- 7809571
TI  - Bibliography of recent literature in sleep research.

PMID- 7809572
TI  - Effect of acute smoking on red blood cell deformability in healthy young and
      elderly non-smokers, and effect of verapamil on age- and acute smoking-induced
      change in red blood cell deformability.
AB  - The effects of age and acute smoking on red blood cell (RBC) deformability in non
      smokers have been studied. RBC ATP levels and in vitro effects of verapamil on
      pre- and post-smoking filterabilities have been determined in an attempt to make
      an approach to the mechanism(s) responsible for the effect of age and acute
      smoking on RBC deformability. Nine young and nine elderly healthy non-smokers
      volunteered to the study. Venous blood samples obtained before and after the
      smoking of one cigarette, were used for ATP analysis and RBC deformability
      determination. ATP was determined enzymatically, deformability was assessed by
      gravity driven microfiltration technique. Verapamil was added to pre- and post
      smoking blood samples to yield a final concentration of 1 mg-1. RBC deformability
      was found to decrease in the elderly group by 19.1% of that of the young group (p
      < 0.001). Acute smoking decreased the filterabilities of RBCs by 15.3% (p <
      0.0001) and 15.9% (p < 0.001) of their pre-smoking values in the young and the
      elderly groups respectively. The smoking-induced decreases in RBC deformability
      were found to be associated with slight but significant decreases (p < 0.02 and p
      < 0.005 for the young and the elderly group respectively) in RBC ATP
      concentrations. Ca2+ channel blockade with verapamil did not produce any
      significant change in pre- and post-smoking filterabilities of RBCs from the
      young group, but improved these variables by 9.7% (p < 0.005) and 10.7% (p <
      0.05) in the elderly group. In conclusion age and smoking are two independent
      factors that affect the deformability of human RBCs.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7809573
TI  - Plasma homocysteine and thiol compound fractions after oral administration of N
      acetylcysteine.
AB  - The total concentration of the atherogenic aminothiol acid homocysteine in plasma
      of healthy volunteers was decreased after oral administration of N-acetylcysteine
      (NAC), whereas the reduced and free (non-protein bound) fractions of homocysteine
      were increased. The decrease of the total fraction varied between 20 and 50% and
      was dose-related. Cysteinylglycine was also decreased after the administration of
      NAC, whereas cysteine did not change. Administration of high amounts of NAC
      probably displaces homocysteine and cysteinylglycine from their protein binding
      sites by disulfide interchange reactions. This leads to the formation of mixed
      low molecular-weight cysteine and NAC disulfides with high renal clearance and
      possibly also increased metabolic bio-availability, thereby eliminating
      homocysteine and cysteinylglycine from plasma. Since only a small amount of
      additional urinary homocysteine was recovered it is likely that this aminothiol
      acid is taken up by the tubular cells and further metabolized.

PMID- 7809574
TI  - Changes in the activities of DNA polymerases in growing rat lungs.
AB  - We hypothesized that cellular proliferation and the capacity to repair DNA damage
      in the lung might differ during the pre- and postnatal periods, because the lung
      is exposed to higher oxygen concentrations and/or various mutagens after birth.
      In order to test this hypothesis, changes in DNA content and the activities of
      DNA polymerase alpha and beta were studied in the lungs of 1-day prenatal to 42
      day postnatal rats. Total DNA polymerase activity reached its highest level at 1
      day prenatal and 1 day after birth. The activity decreased exponentially by 28%
      up to 14 days of age, a change inversely related to the change in DNA content.
      The change in total DNA polymerase activity agreed closely with the change in DNA
      polymerase alpha activity, but not the activity of the beta form, although small
      elevations in both DNA polymerase alpha and beta were observed on day 3, possibly
      reflecting the mechanical effect of delivery. The activity of DNA polymerase beta
      remained relatively constant from 1 day before birth to 21 days after birth,
      varying by only about 5%. From these results, it is concluded that: (1) cellular
      proliferation in the lung is most active during the first 2 weeks after birth as
      supported by the increases in DNA polymerase alpha activity and DNA content, and
      (2) anticipating the oxygen enriched atmosphere after birth, the level of DNA
      polymerase beta, involved in the DNA repair system, is already elevated during
      the prenatal period and remains constant throughout the postnatal period.

PMID- 7809575
TI  - Influence of metabolic control of pregnant diabetics on fetal lung maturity.
AB  - We studied the relationship between the metabolic control of pregnant diabetics
      and fetal lung maturity. In 31 diabetic and 20 normal pregnancies we analysed
      phospholipids in amniotic fluid and glycaemic control parameters. There were no
      differences in amniotic fluid lecithin/sphingomyelin (L/S) and
      phosphatidylinositol/sphingomyelin (PI/S) ratios between pregnant diabetics with
      strict metabolic control and the control group. Pregnant diabetics with poor
      metabolic control had significantly different L/S and PI/S ratios than the normal
      pregnant women. Six women in this group of poorly controlled diabetics had mature
      surfactant in amniotic fluid (L/S > or = 2.7 and presence of
      phosphatidylglycerol) at 32-34 weeks of amenorrhea; the difference was
      significant (p < 0.05) with respect to the control group. These six women had
      recurrent hypoglycaemic episodes (6.4 +/- 1.3 episodes/week) at 14-27 weeks of
      amenorrhea. Our findings suggest that hypoglycaemic stress on the fetus could
      disturb fetal synthesis of pulmonary phospholipids.

PMID- 7809576
TI  - Factors influencing between-laboratory variability of C-reactive protein results
      as evidenced by the Belgian External Quality Assessment(EQA) Scheme.
AB  - Based on results from the Belgian External Quality Assessment (EQA) Scheme, we
      studied the main factors affecting the between-laboratory variation of C-reactive
      protein determination. Participants using homogeneous systems with several
      calibration points generally achieved better performance. Working temperatures
      influenced the results to a lesser extent. The present study stresses the
      importance for EQA organizers to collect more detailed information about CRP
      analytical methods used by the participants. It also suggests that manufacturers
      should be more involved in the management of quality, in particular by striving
      for standardization of the material (kit and calibrator) they produce for CRP
      assay.

PMID- 7809578
TI  - A comparison between two commercial methods for determining carbohydrate
      deficient transferrin (CDT).
AB  - The performance of CDTect (Kabi-Pharmacia, Uppsala, Sweden) and two versions of
      AXIS % CDT (AXIS Biochemicals, Oslo, Norway) for determining carbohydrate
      deficient transferrin (CDT) was examined in 502 consecutive patients admitted to
      the Department of Medicine, Aker University Hospital. The sensitivity for
      detecting an alcohol consumption > or = 50 g/day for the last 4 weeks was 69% for
      CDTect, 65% for AXIS % CDT, version 1 (AX CDT 1) and 50% for AXIS % CDT, version
      2 (AX CDT 2). The specificity at the same level of alcohol consumption, markedly
      differed between the two methods: 92%, 76% and 90% for CDTect, AX CDT 1 and AX
      CDT 2, respectively. The variation coefficient (day-to-day) was 10%, 22% and 10%
      for CDTect, AX CDT 1 and AX CDT 2, respectively.

PMID- 7809577
TI  - Endothelin-1 and cerebral blood flow: influence of hypoxia, hypercapnia and
      indomethacin on circulating endothelin levels in healthy volunteers.
AB  - We investigated the effect of moderate (FiO2 13%) and light hypoxia (FiO2 17%)
      and hypercapnia (CO2 2-4%) with or without indomethacin on circulating levels of
      endothelin/endothelins (ET) and cerebral blood flow (CBF) in healthy volunteers.
      In protocol A, 23 subjects were exposed to moderate hypoxia. In protocol B, 29
      subjects were randomized to one of four groups: (1) placebo, (2) indomethacin,
      (3) indomethacin+light hypoxia and (4) indomethacin+hypercapnia. Indomethacin was
      given as an intravenous bolus dose of 0.4mgkg-1 body weight followed by
      continuous infusion of 0.4mgkg-1h-1 for 6h. Two different FiO2 were chosen, light
      hypoxia in protocol B was chosen due to application of a known cerebral
      vasoconstrictor with unknown effect on cerebral autoregulation. We found, that
      moderate hypoxia (protocol A) induced a significant increase in CBF from 59.0 to
      73.0 ml 100 g-1 brain tissue min-1 (p < 0.00005) with an increase in circulating
      levels of ET from 1.7 to 1.9fmol ml-1 plasma. However, this difference did not
      reach statistical significance (p = 0.14). We found, that indomethacin given
      intravenously (protocol B groups 2-3-4) significantly elevated circulating levels
      of ET from 2.1 to 3.9fmol ml-1 plasma (p < 0.00005) and decreased CBF from 60.5
      to 39.5 ml 100g-1 brain tissue min-1 (p < 0.00005) compared to baseline values.
      Exposure to light hypoxia/hypercapnia in the indomethacin group increased CBF to
      values not significantly different from baseline values. Although there was no
      statistical correlation between ET and CBF with and without indomethacin, our
      results suggest that ET may be involved in the cerebral vasoconstriction produced
      by indomethacin given intravenously.

PMID- 7809579
TI  - Oral S-adenosyl-L-methionine (SAMe) administration enhances bile salt conjugation
      with taurine in patients with liver cirrhosis.
AB  - We investigated whether the oral administration of SAMe influences the hepatic
      availability of sulphur amino acids and the extent of bile salt amidation with
      taurine in liver cirrhosis. Ten patients with cirrhosis (eight Child-Pugh A and 2
      B, aged 48-65 years), were studied before and 2 months after oral SAMe
      administration (800 mg per day). Bile was obtained using a string-test device
      (Entero-test), after gall-bladder contraction with caerulein. No significant
      changes were found in the per cent composition of biliary amino acids, except for
      an increase in glutamic acid (from 3.7 +/- 0.6% before to 6.1 +/- 1.1% after
      SAMe, p = 0.003) and taurine from 2.2 +/- 2.3% (range 0.4-6.8) to 7.2 +/- 9.2%
      (range 0.5-28.1), (NS). HPLC analysis showed a trend towards increased per cent
      tauroconjugation of all individual bile salts, with a significant rise in
      taurochenodeoxycholic acid (from 15.0 +/- 9.4% to 25.3 +/- 9.7%, p = 0.05) and a
      drop in glycocholic acid (from 39.1 +/- 15.3% to 25.3 +/- 9.8%, p = 0.05). These
      data suggest that in the cirrhotic liver exogenous SAMe is partially metabolized
      to taurine, which is used for bile salt amidation.

PMID- 7809581
TI  - Determination of human tumour necrosis factor-alpha (TNF-alpha) by time-resolved
      immunofluorometric assay.
AB  - We have developed a 'sandwich'-type time-resolved immunofluorometric assay (IFMA)
      for tumour necrosis factor alpha (TNF-alpha) using two monoclonal antibodies
      (mAb) and the streptavidin/biotin (SAB) system. In this simple and fast
      streptavidin/biotin IFMA (SAB-IFMA) we used streptavidin coated wells to which we
      added biotinylated mAb for 3 h. After washing, the serum sample was added and
      incubated for 2 h followed by washing. Another monoclonal europium-labelled
      tracer antibody was added and incubated for 1 h, the wells were washed and the
      fluorescence of Eu measured. We tested various assay conditions in order to
      optimize the assay for sensitivity and measuring range. Purification of the
      labelled antibody by hydrophobic interaction chromatography was found to be
      essential to improve sensitivity. With a sample volume of 50 microliters the
      detection limit was 6 ng l-1 and the analytical range large, i.e. 10,000-fold.
      The median concentration in serum from healthy subjects was 12 ng l-1 and the
      reference range < 39 ng l-1. The mean analytical recovery in plasma was 76% and
      in serum 83%. Separation of serum by gel filtration and assay of TNF-alpha in
      fractions showed that the assay also measured the high molecular weight (MW) form
      of TNF-alpha, apparently corresponding to its complex with soluble receptors.
      Advantages of our SAB-IFMA were high sensitivity and low consumption of mAb. The
      assay performance of the SAB-IFMA was compared to two commercially available
      enzyme immunoassays also using the SAB system.

PMID- 7809580
TI  - Lipoproteins do not modulate the tissue factor activity, plasminogen activator or
      tumour necrosis factor production induced by lipopolysaccharide stimulation of
      human monocytes.
AB  - Upon stimulation with lipopolysaccharides (LPS), monocytes are able to produce
      tissue factor (TF), the most powerful physiological procoagulant substance known.
      In several assay systems LPS bound to lipoprotein has been reported to be less
      active than unbound LPS in stimulating monocytes. In the present study the LPS
      induced TF activity was, however, not prevented by lipoproteins (VLDL, LDL, HDL).
      In fact, the very low density (VLDL) fraction further increased the TF inducing
      capacity of LPS. The lipoproteins per se mediated reduced plasminogen activator
      (PA) production in monocytes. LPS had an even more and significant depressing
      effect on PA production, which was not further decreased in the presence of
      lipoproteins. Furthermore, LPS-induced release of tumour necrosis factor (TNF), a
      marker of monocyte activity, was not inhibited by lipoproteins. Our experiments
      suggest that lipoproteins do not render LPS less effective in stimulating TNF
      release, procoagulant and fibrinolytic activities in human monocytes.

PMID- 7809582
TI  - Factitiously low urate recoveries in control sera with the Beckman Synchron
      Systems.
AB  - In the Belgian national external quality assessment scheme, we observed
      significantly lowered recoveries for urate in the group of Beckman Synchron users
      in comparison with the overall median values of the uricase/peroxidase
      colorimetric methods. These effects were linked to control sera of some
      manufacturers and we could demonstrate that these sera contained large amounts of
      pyridoxal-5-phosphate (PLP) as activator for transaminases. By spiking normal
      human serum with increasing PLP concentrations from 62.5 to 1000 mumol l-1, we
      observed a decrease in the urate recovery from 125 mumol l-1 (-11%). At 1000
      mumol l-1 PLP, only 40% of the urate concentration was measured. An explanation
      for this effect was found in the polychromatic corrections of the Beckman Sychron
      system only applied with the Beckman urate method. This study demonstrates that
      EQAS organizers must carefully distinguish in their peer groups, not only the
      analytical principle and the measurement equipment, but also the reagent origin.
      Finally, the use of EQA control sera without PLP addition is strongly recommended
      if these sera are intended to be used as accuracy controls in EQA schemes
      including Beckman Synchron users.

PMID- 7809583
TI  - Calibration of sensory and cognitive judgments: a single model for both.
AB  - In a recent issue of this journal, Winman and Juslin (34, 135-148, 1993) present
      a model of the calibration of subjective probability judgments for sensory
      discrimination tasks. They claim that the model predicts a pervasive
      underconfidence bias observed in such tasks, and present evidence from a training
      experiment that they interpret as supporting the notion that different models are
      needed to describe judgment of confidence in sensory and in cognitive tasks. The
      model is actually part of the more comprehensive decision variable partition
      model of subjective probability calibration that was originally proposed in
      Ferrell and McGoey (Organizational Behavior and Human Performance, 26, 32-53,
      1980). The characteristics of the model are described and it is demonstrated that
      the model does not predict underconfidence, that it is fully compatible with the
      overconfidence frequently found in calibration studies with cognitive tasks, and
      that it well represents experimental results from such studies. It is concluded
      that only a single model is needed for both types of task.

PMID- 7809585
TI  - Thirty-year secular trends in the cognitive abilities of Danish male school
      leavers at a high educational level.
AB  - A nationally representative sample of Danish males finishing school in 1989, or
      shortly before, with a studentereksamen (the highest qualification in the Danish
      school system) was found to score generally lower on a battery of four cognitive
      tests than a comparable sample of Danish males who had taken the same tests
      shortly after finishing school in the late 1950s or early 1960s. This decline
      appears attributable to the increasing proportions of students who obtain the
      studentereksamen and is quite compatible with an overall increase in test scores,
      also found in our data, for the general population over the same time period. For
      those who obtain the studentereksamen, the decline has been most marked in a test
      of verbal analogies. It has been smaller for tests of logical and spatial
      reasoning, and scores on a test of numerical ability have actually improved over
      the 30 years. This differential pattern may be the result of both student changes
      and curricular changes within Danish schools.

PMID- 7809584
TI  - The total workload of male and female white collar workers as related to age,
      occupational level, and number of children.
AB  - A questionnaire assessing various aspects of paid as well as unpaid forms of
      productive activity was mailed to stratified samples of male and female white
      collar workers, approximately matched for educational and occupational level.
      Data from 501 men and 679 women employed full time revealed traditional gender
      differences in terms of main responsibility for household duties, child care etc.
      In keeping with this, women reported higher levels of work overload, stress and
      conflict than men, which increased significantly with the number of children at
      home. The various stress indices reached a peak between the ages of 35 and 39.
      Men reported more autonomy in their paid work whereas women reported more control
      at home. Men and women at the upper managerial levels reported more control over
      their total work situation and less conflict between demands.

PMID- 7809586
TI  - Reliability and validity of mothers' developmental estimates for children between
      4 and 41 months.
AB  - The feasibility of mothers estimating their own children's development is
      explored in this paper. Construction, reliability and validity of a mothers'
      developmental inventory for children from 4 months to 41 months is described. The
      inventory consists of six subtests: Gross Motor, Fine Motor, Language Expression,
      Language Comprehension, Personal-Social Competence and Self Help. A preliminary
      version of the inventory was item analyzed on a sample of 105 mothers of 4 to 37
      months old children. This reduced the inventory to 164 items with satisfactory
      reliability and age discrimination on half-year intervals. The list was cross
      validated on a sample of 275 mothers, for which medians of alpha coefficients for
      the six subtests ranged from 0.69 to 0.96, with most (26 out of 36) coefficients
      being 0.77 or higher. Again, the age discrimination was satisfactory, although
      floor effects appeared on four subtests for children younger than 12 months and
      ceiling effects on two subtests for children older than 24 months.

PMID- 7809587
TI  - Infant intentionality as object directedness: a method for observation.
AB  - It is argued that a definition of intentionality in terms of object directedness
      is more adequate than the traditional definition in terms of goal directedness.
      Inconsistencies in the use of "intentionality" among infant researchers are
      pointed out. A method of observation is explored, based on the definition in
      terms of behavioral object directedness, that takes into account precursors to
      fully-fledged intentional actions by approaching intentionality as a matter of
      degree rather than as an all or none issue. The method, when used on longitudinal
      video recordings of parent-infant interaction, produced results that
      substantiated Trevarthen's observations of infant intentionality before the age
      of six months. Furthermore, the results suggest that the parent's attribution of
      intentions to the infant is based on the perception of the infant's
      intentionality, whether in social interaction or in interaction with "physical"
      objects.

PMID- 7809588
TI  - Prediction accuracy of text recall: ease, effort and familiarity.
AB  - Prediction accuracy of text recall was studied in two experiments. Text
      characteristics (i.e., consistency and distinctiveness) were manipulated in
      Experiment 1, and familiarity with the reading-task in Experiment 2. The results
      were also analyzed and discussed in terms of easy processing (Experiment 1), and
      in terms of increased and more active processing (Experiment 2). Text
      characteristics did not affect prediction accuracy. However, being familiar with
      the reading-task led to good and long-lasting prediction accuracy. Thus, subjects
      reading a school-book text, instructed to learn the contents of it demonstrated
      reliable memory awareness, both for immediate recall and for delay of one week.
      It was also suggested that increased processing demands and active reading
      enhances prediction accuracy.

PMID- 7809589
TI  - [Current malaria management in Switzerland].
AB  - Diagnosis and management of malaria in returning travellers must be treated as an
      emergency. A thorough travel history and a blood examination are prerequisites
      for diagnosis of the infection. Plasmodium vivax, P. ovale and P. malariae
      infections cause febrile illnesses that are usually not dangerous, but P.
      falciparum often causes complications that can be fatal. Hospitalization should
      therefore be considered in the latter cases. The clinical features of the disease
      are often non-specific (fever, headache, myalgia, sweating). Furthermore,
      mitigated and delayed courses of the illness due to sub-therapeutic antimalarial
      drug levels are recorded in patients who have taken incomplete chemosuppression.
      Chloroquine is still the treatment of choice in most cases of P. vivax, P. ovale
      and P. malariae infections. In P. falciparum malaria, chemoresistance in many
      parts of the world requires treatment with other antimalarials. Treatment should
      be started when there is strong suspicion of malaria even before the diagnosis is
      parasitologically confirmed. Quinine is the drug of choice in severe P.
      falciparum malaria. An intravenous loading dose is administered if no previous
      treatment has been given.

PMID- 7809590
TI  - [Balloon valvuloplasty of a discrete subvalvular aortic stenosis].
AB  - We describe the successful percutaneous balloon valvuloplasty of a discrete
      subaortic stenosis in an adult patient. The maximal gradient of 160 mm Hg (mean
      100) was reduced to 45 and 33 mm Hg respectively. The procedure required only one
      overnight hospital stay.

PMID- 7809591
TI  - [Localized pigmented villonodular synovitis: a primary overlooked diagnosis in a
      young female patient].
AB  - Localized pigmented villonodular synovitis is a rare condition of the knee that
      may present with symptoms suggesting internal derangement. We report a case of
      juvenile patient who presented with a 1-year history of signs and symptoms of a
      loose body in the knee. Radiographic examination and MRI were within normal
      limits. The lesion was treated arthroscopically by resection.

PMID- 7809592
TI  - [Tumor-induced anemia and markers of inflammation].
AB  - Anemia of cancer patients is multifactorial but often resembles anemia of chronic
      inflammatory disorders. We investigated the possibility of measurably increased
      parameters of inflammation in the serum of cancer patients and examined the
      correlation of hemoglobin levels, serum iron, and markers of inflammatory
      response in 201 cancer patients. Serum levels of CRP, ferritin, s-IL-2R,
      neopterin levels and TNF were assayed with ELISA tests. Statistically significant
      correlations were found between hemoglobin levels, CRP (Pearson's R = -0.451; p <
      0.0001), serum iron (R = 0.326) and ferritin levels (R = -0.449). No significant
      correlations were seen between hemoglobin levels and neopterin or s-IL-2R. The
      correlation between hemoglobin levels in cancer patients and elevated markers of
      inflammatory responses, such as CRP, suggest that cytokines involved in the
      inflammatory responses may be at least partially responsible, directly or
      indirectly, for anemia in cancer patients.

PMID- 7809593
TI  - Deciphering the breast cancer gene. Experts grapple with the implications of the
      finding.

PMID- 7809594
TI  - The no-name virus. Questions linger after the four corners outbreak.

PMID- 7809595
TI  - Relinquishing relics. 3-D copies of artifacts could stand in for the real thing.

PMID- 7809596
TI  - The new genetic medicines.

PMID- 7809597
TI  - p53 transcriptional activation mediated by coactivators TAFII40 and TAFII60.
AB  - The tumor suppressor protein p53 is a transcriptional regulator that enhances the
      expression of proteins that control cellular proliferation. The multisubunit
      transcription factor IID (TFIID) is thought to be a primary target for site
      specific activators of transcription. Here, a direct interaction between the
      activation domain of p53 and two subunits of the TFIID complex, TAFII40 and
      TAFII60, is reported. A double point mutation in the activation domain of p53
      impaired the ability of this domain to activate transcription and,
      simultaneously, its ability to interact with both TAFII40 and TAFII60.
      Furthermore, a partial TFIID complex containing Drosophila TATA binding protein
      (dTBP), human TAFII250, dTAFII60, and dTAFII40 supported activation by a Gal4-p53
      fusion protein in vitro, whereas TBP or a subcomplex lacking TAFII40 and TAFII60
      did not. Together, these results suggest that TAFII40 and TAFII60 are important
      targets for transmitting activation signals between p53 and the initiation
      complex.

PMID- 7809598
TI  - Article copying.

PMID- 7809599
TI  - Article copying.

PMID- 7809600
TI  - Sunlight and melanoma: an answer from MTS1 (p16)

PMID- 7809601
TI  - Software availability.

PMID- 7809602
TI  - Chiron challenged on hepatitis-C patent.

PMID- 7809603
TI  - Rules would drop need for clinical data.

PMID- 7809604
TI  - Broder to join exodus from NCI.

PMID- 7809606
TI  - Evolution made visible.

PMID- 7809605
TI  - Use of placebo controls in clinical trials disputed.

PMID- 7809608
TI  - The uses of evolutionary biology.

PMID- 7809607
TI  - The mystery of humanity's missing mutations.

PMID- 7809609
TI  - Single cells as biosensors for chemical separations.
AB  - A biosensor system based on the response of living cells was demonstrated that
      can detect specific components of a complex mixture fractionated by a microcolumn
      separation technique. This system uses ligand-receptor binding and signal
      transduction pathways to biochemically amplify the presence of an analyte after
      electrophoretic separation. The transduced signal was measured by means of two
      approaches: (i) fluorescence determination of intracellular calcium
      concentrations in one or more rat PC-12 cells and (ii) measurement of
      transmembrane current in a Xenopus laevis oocyte microinjected with messenger RNA
      that encodes a specific receptor. This analysis system has the potential to
      identify biologically active ligands present in a complex mixture with
      exceptional sensitivity and selectivity.

PMID- 7809610
TI  - Experimental tests of the roles of adaptation, chance, and history in evolution.
AB  - The contributions of adaptation, chance, and history to the evolution of fitness
      and cell size were measured in two separate experiments using bacteria. In both
      experiments, populations propagated in identical environments achieved similar
      fitnesses, regardless of prior history or subsequent chance events. In contrast,
      the evolution of cell size, a trait weakly correlated with fitness, was more
      strongly influenced by history and chance.

PMID- 7809611
TI  - A proficient enzyme.
AB  - Orotic acid is decarboxylated with a half-time (t1/2) of 78 million years in
      neutral aqueous solution at room temperature, as indicated by reactions in quartz
      tubes at elevated temperatures. Spontaneous hydrolysis of phosphodiester bonds,
      such as those present in the backbone of DNA, proceeds even more slowly at high
      temperatures, but the heat of activation is less positive, so that dimethyl
      phosphate is hydrolyzed with a t1/2 of 130,000 years in neutral solution at room
      temperature. These values extend the known range of spontaneous rate constants
      for reactions that are also susceptible to catalysis by enzymes to more than 14
      orders of magnitude. Values of the second-order rate constant kcat/Km for the
      corresponding enzyme reactions are confined to a range of only 600-fold, in
      contrast. Orotidine 5'-phosphate decarboxylase, an extremely proficient enzyme,
      enhances the rate of reaction by a factor of 10(17) and is estimated to bind the
      altered substrate in the transition state with a dissociation constant of less
      than 5 x 10(-24) M.

PMID- 7809613
TI  - "The Duesberg phenomenon": what does it mean?

PMID- 7809612
TI  - Structure-based design of transcription factors.
AB  - Computer modeling suggested that transcription factors with novel sequence
      specificities could be designed by combining known DNA binding domains. This
      structure-based strategy was tested by construction of a fusion protein, ZFHD1,
      that contained zinc fingers 1 and 2 from Zif268, a short polypeptide linker, and
      the homeodomain from Oct-1. The fusion protein bound optimally to a sequence
      containing adjacent homeodomain (TAATTA) and zinc finger (NGGGNG) subsites. When
      fused to an activation domain, ZFHD1 regulated promoter activity in vivo in a
      sequence-specific manner. Analysis of known protein-DNA complexes suggests that
      many other DNA binding proteins could be designed in a similar fashion.

PMID- 7809614
TI  - "The Duesberg phenomenon": what does it mean?

PMID- 7809615
TI  - "The Duesberg phenomenon": what does it mean?

PMID- 7809616
TI  - "The Duesberg phenomenon": what does it mean?

PMID- 7809617
TI  - "The Duesberg phenomenon": what does it mean?

PMID- 7809618
TI  - NSF moves into FastLane to manage flow of grants.

PMID- 7809619
TI  - Bendectin case dismissed.

PMID- 7809620
TI  - Biosphere 2 gets new lease on life from research plan.

PMID- 7809621
TI  - Getting the bugs worked out.

PMID- 7809622
TI  - A new face for the glutamate receptor.

PMID- 7809623
TI  - High turnover of HIV in blood revealed by new studies.

PMID- 7809624
TI  - Big-bang nucleosynthesis and the baryon density of the universe.
AB  - For almost 30 years, the predictions of big-bang nucleosynthesis have been used
      to test the big-bang model to within a fraction of a second of the bang. The
      agreement between the predicted and observed abundances of deuterium, helium-3,
      helium-4, and lithium-7 confirms the standard cosmology model and allows accurate
      determination of the baryon density, between 1.7 x 10(-31) and 4.1 x 10(-31)
      grams per cubic centimeter (corresponding to about 1 to 15 percent of the
      critical density). This measurement of the density of ordinary matter is pivotal
      to the establishment of two dark-matter problems: (i) most of the baryons are
      dark, and (ii) if the total mass density is greater than about 15 percent of the
      critical density, as many determinations indicate, the bulk of the dark matter
      must be "non-baryonic," composed of elementary particles left from the earliest
      moments.

PMID- 7809625
TI  - Rapid accretion and early differentiation of Mars indicated by 142Nd/144Nd in SNC
      meteorites.
AB  - Small differences in the ratio of neodymium-142 to neodymium-144 in early formed
      mantle reservoirs in planetary bodies are the result of in situ decay of the
      extinct radionuclide samarium-146 and can be used to constrain early planetary
      differentiation and therefore the time scale of planetary accretion. The martian
      meteorite Nakhla (approximately 1.3 billion years old), the type sample of the
      nakhlite subgroup of the Shergottite-Nakhlite-Chassigny (SNC) meteorites,
      exhibits a 59 +/- 13 parts per million excess in the ratio of neodymium-142 to
      neodymium-144 relative to normal neodymium. This anomaly records differentiation
      in the martian mantle before 4539 million years ago and implies that Mars
      experienced no giant impacts at any time later than 27 million years after the
      origin of the solar system.

PMID- 7809626
TI  - Segregation in DNA solutions induced by electric fields.
AB  - DNA solutions subjected to an electric field exhibit an instability that leads to
      DNA segregation in aggregates tilted with regard to the field. With the use of
      epifluorescence videomicroscopy, the evolution of DNA patterns in capillaries as
      a function of DNA concentration, DNA size, field strength, and field frequency
      was studied. The field threshold for segregation was decreased when the frequency
      was lowered or when the DNA molecular weight or concentration was increased.
      Aggregation is attributed to an electrohydrodynamic instability triggered by the
      dipole-dipole interaction. This phenomenon explains the failure of earlier
      attempts to separate large DNA in capillaries.

PMID- 7809627
TI  - A salt-sensitive 3'(2'),5'-bisphosphate nucleotidase involved in sulfate
      activation.
AB  - Overexpression of a yeast gene, HAL2, allows the cells to tolerate higher than
      normal extracellular salt concentrations. HAL2 encodes a 3'(2')5'-bisphosphate
      nucleotidase that serves to remove the end products of sulfate transfer during
      cellular metabolism. The enzyme is inhibited by lithium and sodium and is
      activated by potassium. Metabolic systems that are sensitive to salt, as well as
      those governing osmolyte synthesis and ion transport, offer routes by which
      genetic engineering can be used to improve the tolerance of various organisms to
      salt.

PMID- 7809628
TI  - Cleavage of an amide bond by a ribozyme.
AB  - A variant form of a group I ribozyme, optimized by in vitro evolution for its
      ability to catalyze magnesium-dependent phosphoester transfer reactions involving
      DNA substrates, also catalyzes the cleavage of an unactivated alkyl amide when
      that linkage is presented in the context of an oligodeoxynucleotide analog.
      Substrates containing an amide bond that joins either two DNA oligos, or a DNA
      oligo and a short peptide, are cleaved in a magnesium-dependent fashion to
      generate the expected products. The first-order rate constant, kcat, is 0.1 x 10(
      5) min-1 to 1 x 10(-5) min-1 for the DNA-flanked substrates, which corresponds to
      a rate acceleration of more than 10(3) as compared with the uncatalyzed reaction.

PMID- 7809629
TI  - A phagosome-to-cytosol pathway for exogenous antigens presented on MHC class I
      molecules.
AB  - Peptides from endogenous proteins are presented by major histocompatibility
      complex class I molecules, but antigens (Ags) in the extracellular fluids are
      generally not. However, pathogens or particulate Ags that are internalized into
      phagosomes of macrophages (M phi s) stimulate CD8 T cells. The presentation of
      these Ags is resistant to chloroquine but is blocked by inhibitors of the
      proteasome, a mutation in the TAP1-TAP2 transporter, and brefeldin A. Moreover,
      phagocytosis of a ribosomal-inactivating protein inhibited M phi protein
      synthesis. These results demonstrate that M phi s transfer Ags from phagosomes
      into the cytosol and that endogenous and exogenous Ags use a final common pathway
      for class I presentation.

PMID- 7809630
TI  - Requirement of FGF-4 for postimplantation mouse development.
AB  - Fibroblast growth factors (FGFs) are thought to influence many processes in
      vertebrate development because of their diverse sites of expression and wide
      range of biological activities in in vitro culture systems. As a means of
      elucidating embryonic functions of FGF-4, gene targeting was used to generate
      mice harboring a disrupted Fgf4 gene. Embryos homozygous for the null allele
      underwent uterine implantation and induced uterine decidualization but did not
      develop substantially thereafter. As was consistent with their behavior in vivo,
      Fgf4 null embryos cultured in vitro displayed severely impaired proliferation of
      the inner cell mass, whereas growth and differentiation of the inner cell mass
      were rescued when null embryos were cultured in the presence of FGF-4 protein.

PMID- 7809631
TI  - Inhibition of ras-induced proliferation and cellular transformation by p16INK4.
AB  - The cyclin-dependent kinase 4 (CDK4) regulates progression through the G1 phase
      of the cell cycle. The activity of CDK4 is controlled by the opposing effects of
      the D-type cyclin, an activating subunit, and p16INK4, an inhibitory subunit.
      Ectopic expression of p16INK4 blocked entry into S phase of the cell cycle
      induced by oncogenic Ha-Ras, and this block was relieved by coexpression of a
      catalytically inactive CDK4 mutant. Expression of p16INK4 suppressed cellular
      transformation of primary rat embryo fibroblasts by oncogenic Ha-Ras and Myc, but
      not by Ha-Ras and E1a. Together, these observations provide direct evidence that
      p16INK4 can inhibit cell growth.

PMID- 7809632
TI  - Assessing molecular phylogenies.

PMID- 7809634
TI  - Delayed helix formation of mutant collagen.

PMID- 7809633
TI  - Assessing molecular phylogenies.

PMID- 7809635
TI  - [Pathomorphology, stability and classification of wedge compression fractures of
      the thoracolumbar spine].
AB  - Compression fractures with anterior wedging of the vertebral body are the most
      frequent fractures of the thoraco-lumbal spine. As yet, there is no fracture
      classification that has achieved general clinical acceptance. A classification is
      presented that defines fractures as A, B, and C types, according to their
      pathomorphology and mechanical stability. The main types are subdivided into A1
      A2, B1-B2 and C1-C2. The A fractures incorporated a compression lesion of the
      anterior column with minimal or moderate loss of anterior height of the vertebral
      body. An intact intervertebral disc defines the A1 lesion. With loss of disc
      function through disc rupture into the fractured body, the vertebral segment is
      biomechanically destabilized and the lesion is classified as A2. The B-type wedge
      compression fracture defines a disc and bone lesion of the anterior column with
      severe wedging combined with a distraction lesion of the posterior column
      involving mostly ligaments. Not infrequently, the middle column presents with a
      dorso-cranial wall fragment, which may be dislocated into the spinal but without
      endangering the cord. Isolated lesions of the anterior and posterior columns are
      considered B1 lesions. B2 lesions incorporate an additional stable osseous lesion
      of the middle column. Wedge compression fractures of the C type are mechanically
      and neurologically unstable three-column lesions producing cord compression by
      way of dislocated fragments of the dorso-cranial vertebral body, which
      compromises the spinal canal. C1 fractures are like B fractures in the degree of
      severity of the anterior and posterior column lesions.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7809636
TI  - [Biomechanical comparison of various emergency stabilization measures of the
      pelvic ring].
AB  - Massive bleeding with shock is still the most frequent reason for early death
      after complex pelvic trauma. For hemostasis, fracture stabilization in the pelvic
      ring is an important aspect. By use of the external fixator and introduction of
      emergency pelvic c-clamps, attempts were made to include pelvic ring
      stabilization on the early resuscitation algorithm. This biomechanical study
      compared a simple anterior external fixator (one supraacetabular pin on each
      side), the emergency pelvic c-clamp (Ganz) and the Browner modification of the
      clamp ("ACE clamp"). Two fresh-frozen human cadaver pelves were loaded in a one
      leg stance model. The displacement and rotations on the site with the fracture
      were measured with a 3D measurement system. Fracture models included a Tile type
      B injury and two Tile type C instabilities (pure SI dislocation; transforaminal
      sacrum fracture). In type B injuries all methods withstood loading with 100% of
      the body weight (640/700 N). In C-type injuries with SI dislocation the external
      fixator showed no significant holding force, whereas the two c-clamps withstood
      loading of 112 N and 160 N. In the transforaminal fracture model no one method
      withstood a load of more than 40 N. The combination of the clamps with the
      external fixator increased the holding strength to 66 N and 103 N. Although a
      single-leg-stance model does not reflect the emergency situation, in which the
      patient is normally in a supine position, the data recorded are comparable to
      those observed in earlier investigations.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7809637
TI  - Use of the unilateral external fixator (monofixator) in fracture treatment:
      experience in 50 fractures.
AB  - From 1988 to 1992, a total of 50 fractures with associated soft tissue lesions
      were treated with a unilateral external fixator (monofixator). The location of
      the fracture was the tibia in 39 cases, the pelvis in 5 cases, the femur in 4
      cases, and the ankle and the humerus in 1 patient each. There were 22 open
      fractures (56%). Unproblematic healing with the monofixator was achieved in 69.2%
      of tibial fractures after a mean healing time of 18.2 weeks. Axial dynamic
      compression was performed in 18 tibial fractures. Planned reosteosynthesis was
      performed in 8 tibial fractures (20%). No late problems were seen after secondary
      internal osteosynthesis. Complications with the monofixator in tibial fracture
      treatment were refracture in 3 patients, pin track infection in 3 patients and
      hypertrophic pseudarthrosis in 1 patient. The monofixator provides safe and
      stable fixation in lower limb fractures with severe associated soft tissue
      trauma. In unstable pelvic and femoral fractures, satisfactory reduction and
      stabilisation can be achieved, mostly lasting until definitive osteosynthesis is
      possible.

PMID- 7809638
TI  - [Bridging long tibial shaft defects by partially demineralized bone matrix].
AB  - The problems arising from the transplantation of autogenic and allogenic bone
      have significantly limited the use of these methods. Hence, there is an ever
      increasing demand for suitable transplant materials that could be readily
      available to orthopaedic surgeons throughout the country. Although the advantages
      of demineralized bone matrix over allogenic cancellous bone have been shown in
      numerous experimental studies, its broad clinical application has so far been
      limited. The purpose of this study was to investigate the osteogenic properties
      of partially demineralized bone matrix in clinically relevant and realistic
      conditions. Tibial defects 5 cm in length in 24 merino sheep were bridged by way
      of medullary nailing and filled with various preparations of bone matrix.
      Cortical bone displaying poor vascularization and rotation instability of the
      osteosynthesis ensured extremely difficult testing conditions for the transplant.
      Postoperatively, the extent of new bone formation was evaluated by means of
      regular X-ray examinations over a period of 12-20 weeks. In addition,
      histological, fluorescent-optical and microradiographic examinations of the final
      specimen were carried out. Good new bone formation regularly followed the
      transplantation of partially demineralized bone matrix with a particle size of
      750 microns. Complete bridging of the defect was achieved when small amounts of
      bone marrow were added. The use of bone matrix with a smaller or larger particle
      size did not influence the rate of new bone formation perceptibly.

PMID- 7809639
TI  - [Prognosis of spongiosa-plasty of the fractured tibial shaft].
AB  - Records of 97 patients who had undergone a total of 171 cancellous bone grafting
      procedures from 1971 to 1988 were analysed with respect to promotion of bony
      healing. It was found that 50 patients had undergone 1 grafting procedure each in
      the tibia, while 47 patients had each undergone 2-5 bone grafting procedures.
      Therefore only every second procedure at best could be considered as successful.
      Predictors for unsuccessful grafting were found to be large bone defects, poor
      vascularization and, especially, infection. Primary grafting was related to more
      problems in terms of uneventful bone healing than was "postprimary" grafting
      after 3 and more weeks after accident. We therefore recommend delayed grafting in
      cases of fractures with soft tissue ruptures. In all cases of segmental bone loss
      multiple bone grafting procedures should now be carefully compared with the
      advantages of segmental bone transport techniques.

PMID- 7809640
TI  - [The atypical C-malleolar fracture].
AB  - Fractures of the ankle in adults are very common. Like every intraarticular
      fracture, they require perfect reduction and stable fixation to guarantee a good
      result. In most cases this can only be achieved by open treatment. The
      classification of ankle fractures according to Weber depends upon whether the
      fibular fracture is below (type A) at (type B) or above (type C) the syndesmosis.
      This classification also defines the importance of the tibio-fibular ligaments.
      From 1978 to 1992 more than 1000 ankle fractures were treated in our clinic by
      open reduction and fixation: 72 were type C ankle fractures, and the rest, either
      type A or type B fractures. When we reviewed our type C fractures we found 9
      patients with so-called atypical type C fractures; these have an atypical
      fracture pattern insofar as a fracture of the medial malleolus is combined with
      tibiofibular ligament lesion and there is no fibula fracture. Definition,
      diagnosis, treatment and results are presented in this publication.

PMID- 7809641
TI  - [A comparison of 2 methods of plastic cast fixation in treatment of loco classico
      radius fracture. A prospective, randomized study].
AB  - The purpose of this study was to compare the functional and radiological result
      of two different positions of the wrist in a plaster cast following Colles'
      fracture. For this prospective study, each of 50 patients with type A 2.2, A 3.3,
      C 1.2 or C 2.2 (AO classification) fractures of the radius was randomly assigned
      to one of two groups. Both groups were treated in the same way as far as
      anaesthesia and reduction were concerned. The only difference in treatment lay in
      the position of fixation in plaster. In group 1 the wrist was immobilized in
      neutral flexion-extension. In group 2 the wrist was dorsiflexed 20 degrees, while
      the carpus was pushed in a volar direction by an impression in the plaster cast.
      At review 2-7 years after the accidents, the two groups were compared with
      reference to symptoms, range of motion at the wrist, power of first closure and
      radiographic appearance. In group 1 there were 5 patients with significant
      disability, compared with only 1 in group 2. A significant difference was found
      in the range of movement between the two groups for flexion and ulnar abduction
      (p < 0.01). The loss of power of first clenching (difference between injured and
      healthy hand) was 6.2 mmHg for group 1 and 3.8 mmHg for group 2 (not
      significant). The radiographic examination showed significant differences both in
      sagittal inclination (p < 0.001) and in radial shortening (p < 0.05).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7809642
TI  - Anatomy and clinical use of posterior interosseous island forearm flap.
AB  - Posterior interosseous island flap of the forearm is still not widely known. It
      deserves more attention as a useful means of reconstruction on the dorsal side of
      the hand up to the PIP joints of the fingers. The technique is relatively easy,
      and the anatomy is quite consistent, as described. Tactile sensation can be re
      established, and infection cavities can be filled up. Two cases are illustrated
      as examples.

PMID- 7809643
TI  - Perforation of the small intestine caused by fixation plate penetration into the
      abdomen.
AB  - The authors report a case of intestinal loop penetration and peritonitis caused
      by penetration of the tip of the fixation into the abdominal cavity after
      internal fixation of an unstable intertrochanteric fracture. Complete regression
      of acute infection was achieved by suturing the intestinal wound, removing the
      internal fixation device and administering systemic and local antibiotic therapy.

PMID- 7809644
TI  - Tithonus.

PMID- 7809645
TI  - Case of the season. Pneumoperitoneum secondary to barotrauma.

PMID- 7809646
TI  - Esophageal motility disorders.

PMID- 7809647
TI  - Reflux esophagitis and Barrett's esophagus.

PMID- 7809648
TI  - Infectious esophagitis.

PMID- 7809650
TI  - Staging of esophageal cancer: computed tomography, magnetic resonance imaging,
      and endoscopic ultrasound.

PMID- 7809649
TI  - Tumors of the esophagus.

PMID- 7809651
TI  - Adenocarcinoma of the esophagus and gastroesophageal junction.

PMID- 7809652
TI  - Esophageal trauma.

PMID- 7809653
TI  - The postoperative esophagus.

PMID- 7809654
TI  - Experimental treatment, values and rationing.

PMID- 7809655
TI  - Contradictions in women's health care provision: a case study of attendance for
      breast cancer screening.
AB  - Breast cancer screening facilities operated by the Ontario Breast Screening
      Program (OBSP) have recently been added to the existing geography of diagnostic
      mammography facilities in hospitals and private clinics in Eastern Ontario. While
      diagnostic facilities require a physician's referral for access, the new centres
      offer mammograms by self-referral. Other work has shown the utilization of
      mammography screening services to be quite low despite widespread acceptance of
      early diagnosis through mammographic screening as the best method to lower breast
      cancer mortality. Major findings are that spatial variation does exist in
      attendance rates in the townships and census tracts surrounding the screening
      centre. At the regional level, physician referral patterns and the presence of
      local diagnostic mammography units appear to affect the uptake of screening at
      the Kingston facility. The individual level analysis confirms the importance of
      the primary care physician's referral with two-thirds of the client sample
      indicating that they were referred for screening by their family physician. The
      sample of clients are also very mobile women who have comparatively greater
      access to financial resources than other women of screening age. The results of
      ecological and individual level analyses of attendance at OBSP's Kingston Centre
      reveal contradictions in the provision of this service. Spatially, the centres
      follow a location pattern of a much higher order health facility yet women are
      expected to include screening as part of their routine care. Attenders at the
      Centre were found to be of higher socioeconomic status, married and have access
      to a private automobile. The finding that the primary care physician's referral
      is an important prerequisite for attendance raises questions about the
      feasibility of providing health care for women which encourages individual
      responsibility for health within the existing paternalistic health care system.

PMID- 7809656
TI  - Primary health care in Zimbabwe: can it survive? An exploration of the political
      and historical developments affecting the implementation of PHC.
AB  - Using a multi-level perspective, this paper examines the structural constraints
      and conflicting perspectives affecting the implementation of Primary Health Care
      (PHC) in Zimbabwe. The analysis of these factors and processes is made by viewing
      the situation from the different perspectives, perceptions and actions of the
      state, the health workers and the population. It is argued that the continuing
      structural inequalities, the bureaucratic and centralization tendencies, the
      historical development and colonial transplantation of biomedical practice, and
      the de facto lack of support by government, constrain the implementation of PHC.

PMID- 7809657
TI  - Patterns of class inequality in health through the lifespan: class gradients at
      15, 35 and 55 years in the west of Scotland.
AB  - Data confirming the existence of social inequalities in health have continued to
      accumulate since the Black Report reported class inequalities across a broad
      range of causes of mortality, with an increasing emphasis on indicators of
      morbidity and current health status. Although evidence of continuing inequalities
      mounts, elucidation of underlying mechanisms generating and maintaining such
      inequalities has been more elusive, and much of the debate has oscillated from
      the very broad to the very specific. In this paper, the class patterning of a
      range of non-fatal indicators of health are modelled in an attempt to outline
      first the adequacy of models of linear relationships for this range of measures,
      and secondly, the extent to which these are generalizable across a series of
      age/sex subgroups and across different domains of health. Data are presented here
      for representative community samples of men and women in adolescence, early- and
      late-midlife. While orderly relationships between social class and health were
      seen for the majority of the measures considered; the detailed patterns show
      considerable diversity. Thus for some aspects of health, notably height (itself
      often heralded as a broad indicator of health and early life experience), common
      class gradients were observed for both sexes at each of the stages of the life
      course examined. For others (notably mental health and presence of chronic
      illness), gradients were evident in later life but not in adolescence. Others
      still showed sex but not age differences in class patterning (typically measures
      of body shape), or no clear patterns (notably blood pressure and consultations
      with general practitioners). The current analysis draws attention to the
      consistency of gradients in early- and late-midlife, which are apparent despite
      the marked increase in the burden of poorer health which manifests between these
      life stages for almost all indicators of health (an exception being mental
      health). The challenges which this presents for understanding the mechanisms and
      processes which have been candidate explanations for social inequalities in
      health are discussed.

PMID- 7809658
TI  - Will AIDS be contained within U.S. minority urban populations?
AB  - Recent empirical research, and a simple stochastic modeling exercise, suggest
      that affluent suburban communities are at increased risk for the diffusion of HIV
      from present inner city epicenters, while the 'core group' construct of sexually
      transmitted disease theory suggests, somewhat counter-intuitively, that the
      hypercongregated and strongly self-interacting nature of affluent heterosexual
      elites in the U.S. places them at significant and increasing risk as well. In
      turn, a growing body of work strongly associates high HIV prevalence in minority
      urban populations with the processes of coupled physical and social
      disintegration which have produced the now-common and politically-generated
      'hollowed out' pattern of U.S. cities. We conclude that a return to the
      principles of the Great Reform Movement, which first brought public health and
      public order to U.S. urban areas, is a necessary, but at present largely
      unrecognized, component to any successful national program to control AIDS in the
      United States, and particularly to stem the diffusion of HIV into heterosexual
      populations outside present diseases epicenters.

PMID- 7809659
TI  - Perceptions and treatment of intestinal worms in rural Bangladesh: local
      differences in knowledge and behaviour.
AB  - A survey was conducted on 131 mothers in rural Bangladesh to examine knowledge
      and perceptions of helminth infection in relation to use of health facilities and
      treatment-seeking behaviour. Almost all respondents considered worms to be a
      cause of bad health and a high percentage of mothers had obtained deworming
      treatment for their children. However, marked differences were found in mothers'
      descriptions of the causes and prevention of helminth infection in two adjacent
      areas; Pullakandi and Shekpara. The discrepancies in biomedical knowledge
      corresponded with differences in treatment-seeking behaviour in the two areas.
      All households in the area had access to free deworming treatment provided by a
      health clinic, but this facility was predominantly used by women living nearby in
      Pullakandi. Because of the cultural and social constraints on female activities,
      women living further from the clinic, in Shekpara, preferred to send their
      husbands to a pharmacy in the nearby town to buy deworming treatment. As a
      consequence, these households were at a relative disadvantage in respect of the
      low exposure of women to health education and the greater financial cost of
      deworming treatment. The study highlights the influences of social and cultural
      factors on treatment-seeking behaviour, which in turn affect women's exposure to
      health education and biomedical knowledge of helminths. Further questions are
      raised, however, on the ability of women to implement preventive measures and the
      impact of health education on rates of parasitic infection.

PMID- 7809660
TI  - A comparative study of patient satisfaction with health care in Japan and the
      United States.
AB  - Patient satisfaction with medical care received at selected medical facilities in
      the United States (895 patients) and in Japan (856 patients) was compared using
      self-administered questionnaires. In each country, patients at a large government
      hospital and a smaller affiliated clinic were surveyed. Patients responded to
      questions concerning specific aspects of medical care, general satisfaction with
      the care received, waiting time to see the physician and time spent with the
      physician. Results suggest that patients at study sites in both countries were
      generally satisfied with the medical care they received. However, American
      patients were more likely to report satisfaction than their Japanese counterparts
      on each dimension of health care measured. The largest discrepancies were found
      in satisfaction with waiting time to see the doctor and time spent with the
      doctor. Stepwise discriminant analyses indicated that provider skill may be the
      most important predictor of overall satisfaction with medical care in both
      countries. These results are discussed in the framework of the underlying health
      care system.

PMID- 7809661
TI  - Traditional uvulectomy in Niger: a public health problem?
AB  - Although traditional uvulectomy, a procedure which consists of cutting away a
      part of the uvula, has been reported in several sub-Saharan African countries, in
      Maghreb and in Israel, epidemiological and anthropological data on this practice
      are rare. Severe complications may require hospitalization. The goal of this
      study was to assess the prevalence of this traditional procedure in Niamey,
      capital of Niger, the incidence of its severe complications and the beliefs and
      practices related to it. By the age of 5, 19.6% of the children in our survey had
      undergone uvulectomy. Severe complications of uvulectomy represented 7.8/1000
      cases of hospitalization for children under 15 years of age. Complications were
      infections (including tetanus), hemorrhage and passage of the cut piece of uvula
      further down the respiratory tract. The children who had undergone uvulectomy
      belonged significantly more often to the Hausa ethnic group (66.2%) than to the
      majority Zarma ethnic group (18.3%) or to the other ethnic groups (15.5%). This
      can be explained by the fact that, in some Hausa subgroups, uvulectomy is
      systematically performed on the 7th day after birth, during the naming ceremony,
      to prevent death due to a 'swelling of the uvula'. In the other Hausa sub-groups
      and in the other ethnic groups, uvulectomy is solely a curative practice, both
      for children and adults, for vomiting, diarrhea, anorexia, the child's rejection
      of the breast, growth retardation and fever. Uvulectomy is performed in Niger by
      the barbers, whose functions are also to perform specialized surgery. These
      traditional surgeons claim there is no risk to this practice.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7809662
TI  - Health or healthy: why people are not sick in a southern Ontarian town.
AB  - The purpose of this paper is to explore 'being healthy' and what it means to
      people living in a small Ontarian town. It begins by setting out different
      definitions of health, concluding that 'being healthy' may help in understanding
      how we see ourselves and others in the world. After briefly discussing the site
      and method of investigation, the paper runs to drawing the distinction between
      health and 'being healthy' empirically. It goes on to examine what respondents
      see as shaping healthiness, contrasting this with current determinants of health
      views. There follows discussion on how 'being healthy' is negotiated for the self
      and how it is viewed in others. 'Being healthy' is seen as a moral code that is
      vital for 'normal' societal membership. Individuals are seen as negotiating,
      through use of the 'sick role', the cause of their health status in order to
      maintain healthiness and their place-in-the-world. If cause is linked to
      individual behaviour, then the individual is seen as being at fault for his/her
      illness, is unhealthy and therefore deviant. The paper concludes by revising the
      conceptualization of health.

PMID- 7809663
TI  - Psychosocial effects of PCB contamination and remediation: the case of
      Smithville, Ontario.
AB  - A cross-sectional study design was used to investigate psychosocial effects in
      the population exposed to PCB contamination and remediation in Smithville,
      Ontario, Canada. Psychosocial effects were defined as the complex of distress,
      dysfunction and disability manifested in a wide range of psychological, social
      and behavioural outcomes as a consequence of actual or perceived contamination.
      This paper describes the results of logistic regression analyses conducted to
      investigate the determinants of psychosocial effects of exposure. The data come
      from an epidemiologic survey of a sample (N = 272) of Smithville households
      within 3 km of the site, and a sample from a matched comparison community (N =
      263). Two types of outcome variables were used as indicators of psychosocial
      effects. Scores on the general measures of psychosocial health and well-being
      (the GHQ-20 and the somatic complaints checklist of the SCL-90) for the
      Smithville sample did not differ from those expected in a 'normal' population,
      nor did they differ from those in the comparison community. Scores on these
      outcomes were associated with plausibly linked independent variables, but were
      not associated with exposure to the PCB site. Results for site-specific outcome
      measures (concern and health concern) showed that moderate levels of concern
      reported by Smithville respondents were explained by concern about another local
      hazardous waste issue and could not be explained by PCB site exposure. We
      conclude from these results that local community context exerts an important
      influence on psychosocial effects of environmental contamination. Furthermore,
      the types of outcome measures employed and the timing of the research in the
      context of the site history were important factors in our ability to detect
      psychosocial effects of the PCB contamination and remediation in Smithville.

PMID- 7809665
TI  - Growth monitoring and the promotion of breast feeding.

PMID- 7809664
TI  - User charges for rural health services in Papua New Guinea.
AB  - This paper reports on a review of user charges for health services in rural areas
      of Papua New Guinea. Facilities implementing both fee for service and community
      risk sharing schemes were studied. This study found that there is a lack of any
      policy framework or practical guidelines on cost recovery. In some areas fees are
      being used as a fiscal tool rather than to further health policy. This study from
      Papua New Guinea raises serious questions about the virtue of cost recovery for
      health services in rural areas. Equity is an issue and the fees are creating a
      barrier both for entry and continuation in the health system; accountability is
      poor, and issues of cross subsidization are not addressed; fee revenues from
      rural health services are small and primarily of local significance; and are not
      being used to improve quality of health services. Cost recovery schemes in rural
      areas have the potential to provide a valuable contributory source of income to
      operate and improve health services. In practice, few are achieving this. It is
      concluded that health sector financing focus could be more fruitfully directed to
      financing mechanisms with greater potential to improve and expand health
      services.

PMID- 7809666
TI  - [Depression and maternity].

PMID- 7809667
TI  - [Puerperal psychoses].

PMID- 7809668
TI  - [The suffering of infants of psychotic mothers].

PMID- 7809669
TI  - [Indications for joint mother-baby psychiatric hospitalization].

PMID- 7809670
TI  - [Mother-baby joint psychiatric hospitalization: a specific plan].

PMID- 7809671
TI  - [The nurse's role].

PMID- 7809672
TI  - [Reconciling strategy with pedagogy].

PMID- 7809673
TI  - [Sexology and somatotherapies].

PMID- 7809674
TI  - [To become a mother: psychological aspects of motherhood].

PMID- 7809676
TI  - [Crisis and the sector].

PMID- 7809675
TI  - [The Good Savior Foundation at Alby].

PMID- 7809677
TI  - [Mental health. An evolution of nursing practice].

PMID- 7809678
TI  - [Activism at admission].

PMID- 7809680
TI  - [Emergencies in pediatric psychiatry].

PMID- 7809679
TI  - [Nursing at the alcohol withdrawal hospital Saint Salvadou].

PMID- 7809681
TI  - [Role of a specific psychogeriatric disposition].

PMID- 7809682
TI  - [The concept of emergency in psychiatry. The crisis at admission].

PMID- 7809683
TI  - [Studying at the psychiatric emergency department. A challenge for nursing
      education].

PMID- 7809684
TI  - [Theophile Roussel. A philanthropist and an institution which will soon be 100
      years old].

PMID- 7809685
TI  - [The aged and demented. Studio for psychophysical activities].

PMID- 7809686
TI  - [State of siege].

PMID- 7809688
TI  - [Hommage to Pierre Sans. The receiving family].

PMID- 7809687
TI  - [The therapeutic family reception. General principles].

PMID- 7809689
TI  - [Helene's and Danielle's family placement].

PMID- 7809690
TI  - [Role and function of the nursing team].

PMID- 7809691
TI  - [The patients taken in for treatment].

PMID- 7809692
TI  - [Reception by the family. Accompanying the patient].

PMID- 7809693
TI  - [Theory of residential therapy].

PMID- 7809694
TI  - [Looking for the rules of our profession].

PMID- 7809695
TI  - [Family reception. Presentation and functioning of the team].

PMID- 7809696
TI  - [A request to listen to].

PMID- 7809697
TI  - [The law of 1990 in question].

PMID- 7809698
TI  - [Legal and regulatory aspects in everyday life].

PMID- 7809699
TI  - [Consent of the psychotic patient].

PMID- 7809700
TI  - [Nursing care and everyday ethics].

PMID- 7809701
TI  - [Evaluation of new drugs].

PMID- 7809702
TI  - [Knowledge, clinical work, what information?].

PMID- 7809703
TI  - [The technique of humid compresses].

PMID- 7809704
TI  - [Music in a care project for the elderly].

PMID- 7809705
TI  - [From questioning to the adaptation of nursing concepts].

PMID- 7809706
TI  - [Ethics and the rights of the mental patient].

PMID- 7809707
TI  - [Importance of electroconvulsive therapy].

PMID- 7809709
TI  - [Legislation, wishes and consent].

PMID- 7809708
TI  - ["I have been sad from birth"].

PMID- 7809710
TI  - [The studio for expression by design and painting].

PMID- 7809711
TI  - [Dreaming, fantasizing, cutting across the collage technique].

PMID- 7809712
TI  - [Finality and fate of a marionette].

PMID- 7809713
TI  - [Artistic mediation by the theater].

PMID- 7809715
TI  - [A theater troupe at the hospital].

PMID- 7809716
TI  - [Writings by nurses].

PMID- 7809714
TI  - [Reflections on art therapy].

PMID- 7809717
TI  - [A severe weight loss].

PMID- 7809718
TI  - [Art therapy today].

PMID- 7809720
TI  - [Massage ... messages].

PMID- 7809719
TI  - [Attachment, detachment].

PMID- 7809722
TI  - [From fork to paintbrush. Ergotherapy].

PMID- 7809723
TI  - [Anorexia, a mask of the imaginative and creative life].

PMID- 7809721
TI  - [Catherine of Siena, doctor of the church].

PMID- 7809724
TI  - [The anorexic patient and her body: a relaxation group].

PMID- 7809725
TI  - [From a helping relationship to a therapeutic one].

PMID- 7809726
TI  - [Anorexia nervosa: current data].

PMID- 7809727
TI  - [Neuro-linguistic programming. Support in the helping relationship].

PMID- 7809728
TI  - [An aggressive patient].

PMID- 7809729
TI  - [Swimming pool and therapy].

PMID- 7809730
TI  - [Climbing and the birth of speech].

PMID- 7809731
TI  - [A fantasy for our patients].

PMID- 7809732
TI  - [The horse: more than recreation].

PMID- 7809733
TI  - [Autistic patients, nurses and painting].

PMID- 7809735
TI  - [A toy in their bundle. From image to object].

PMID- 7809734
TI  - [The mime in everyday life or intention towards expression].

PMID- 7809736
TI  - [The autistic adult. A new concept in public psychiatry].

PMID- 7809737
TI  - [Towards epistemiological research].

PMID- 7809738
TI  - [Concept of care within a unit].

PMID- 7809739
TI  - [Art therapy and mental retardation].

PMID- 7809740
TI  - [A disoriented woman with memory troubles].

PMID- 7809741
TI  - [A general physician among the autists].

PMID- 7809742
TI  - [Genesis of care for the autistic].

PMID- 7809743
TI  - [Autism in everyday life].

PMID- 7809744
TI  - The use of the percentage change in Oswestry Disability Index score as an outcome
      measure in lumbar spinal surgery.
AB  - STUDY DESIGN: A retrospective analysis of the change in the Oswestry Low Back
      Pain Disability Questionnaire in a heterogeneous group of 144 operatively managed
      patients was undertaken to examine the change in disability index as an outcome
      measure. OBJECTIVES: To establish the percent change in disability index as an
      outcome measure able to identify risk factors for poor results in lumbar spinal
      surgery. METHODS: Epidemiologic, diagnostic, and surgical variables were examined
      as risk factors using step-wise multiple linear regression analysis at both
      follow-up times (6 months and 2 years), with percent change in disability index
      used as the outcome measure. RESULTS: At 6-months follow-up, previous surgery,
      female gender, workers' compensation, a lower initial disability index score,
      increasing age, and spinal fusion alone as an operative procedure were
      independently and significantly negatively correlated with outcome. Further
      analysis revealed that for patients with spinal canal stenosis, the magnitude of
      the initial disability index did not correlate with outcome, whereas patients
      with low back pain or a prolapsed intervertebral disc fared better if they had
      high initial disability scores. Data at 2-years follow-up were less adequate.
      However, previous surgery on the spine and low initial disability score were
      significant negative predictors of outcome at 6-month and 2-year follow-up.
      CONCLUSIONS: The findings indicate that the absolute value and change in these
      scores after surgery vary from patient to patient, but that their percentage
      change is likely to be the best marker of outcome when such subjective scoring
      systems are used.

PMID- 7809745
TI  - Postoperative bone re-growth in lumbar spinal stenosis. A multivariate analysis
      of 48 patients.
AB  - STUDY DESIGN: Forty-eight patients who underwent posterior decompressive surgery
      for lumbar spinal stenosis were studied. The effect of bone re-growth after
      posterior decompression in lumbar spinal stenosis on clinical outcome and the
      factors promoting the bone re-growth were investigated with a multivariate
      analysis model. METHODS: Bone re-growth at the sites operated upon was evaluated
      as a percentage of re-growth of the original laminectomy site based upon plain
      radiographs. The degree of bone re-growth was classified into four groups: 1) no
      significant re-growth (Group I, bone regrowth rate 10% or less); mild (Group II,
      11% to 40%), moderate (Group III, 41% to 70%), and marked (Group IV, 71% to
      100%). The average follow-up period was 4.5 years (range, 2 to 7 years). RESULTS:
      No significant bone re-growth was shown in 6% of the patients. Mild re-growth was
      shown in 50%, moderate re-growth in 29%, and marked re-growth in 15%. A
      multivariate analysis indicated that a total block in the preoperative myelogram,
      a follow-up period of more than 5 years, decompression at more than three spinal
      levels, and age under 60 years were associated with moderate or marked bone re
      growth. Spinal instability accelerated the bone re-growth mainly in the mid and
      later follow-up intervals. Spinal levels adjacent to a fusion showed more bone re
      growth. Patients with moderate and marked bone re-growth had poorer clinical
      outcomes than those with no significant and mild bone re-growth. CONCLUSION: Bone
      re-growth in a surgical defect will occur in most patients after posterior
      decompression. Moderate and marked postoperative bone re-growth are possibly
      related to recurrence of neurologic symptoms in the middle of and later on in
      follow-up periods.

PMID- 7809746
TI  - Unconventional pedicle spinal instrumentation. The Bombay experience.
AB  - STUDY DESIGN: A retrospective study of all patients who underwent spinal fusion
      between 1986 to 1989 with inexpensive, locally made unconventional pedicle spinal
      instrumentation systems was undertaken. Implants were made with passivated 316L
      stainless steel, and a single level of instrumentation cost +f430. OBJECTIVES: To
      demonstrate that simple, cheap pedicle instrumentation systems are as effective
      as the conventionally available expensive systems, provided proper anterior
      column support is maintained. METHODS: Ninety out of 102 patients were available
      for review. Average follow-up was 41 months (range, 22 to 60 months). Implant
      failures, screw placement, fusion rates, infection, neurologic deficit due to the
      implant, patient satisfaction, and the benefit of anterior column grafting with
      the unconventional pedicle spinal instrumentation systems in the long term were
      evaluated. RESULTS: Forty-four out of 467 screws failed (9%) in 16 patients,
      seven of whom were symptomatic. There were no plate failures. On comparing burst
      fractures with (n = 12) and without (n = 10) anterior column grafting, the latter
      group had a significant increase in implant failures, loss of sagittal alignment,
      and the time required to fusion. Overall, fusion occurred within 6.5 months.
      CONCLUSIONS: Anterior column reconstruction in anterior column deficient spines
      will re-create the normal biomechanics and significantly reduce the incidence of
      implant failures and loss of sagittal alignment with these systems. Pedicle screw
      failure in itself is not necessarily associated with a bad result. These
      inexpensive, locally made unconventional systems, with the proper understanding
      of biomechanics and creation of appropriate load-sharing constructs, are as good
      as the conventional systems available today.

PMID- 7809747
TI  - Biomechanical, radiologic, and histopathologic correlations in the pathogenesis
      of experimental intervertebral disc disease.
AB  - STUDY DESIGN: The desert sand rat, an animal model for spinal degenerative disc
      disease, was studied for biomechanical, histologic, and radiographic
      characteristics. Load deformation curves with peak force and force decay,
      hematoxylin-eosin-stained sections, and lateral radiographs were correlated.
      OBJECTIVES: The hypothesis that the subchondral bone response preceded or
      contributed to the degenerative disc disease seen in the desert sand rat was
      tested. SUMMARY OF BACKGROUND DATA: Intervertebral disc disease spontaneously
      develops in the desert sand rat during its lifetime. Approximately 50% will have
      significant disc disease by age 18 months. Previous studies have found metabolic
      and histologic changes associated with intervertebral disc degeneration in the
      sand rat. METHODS: Desert sand rats were killed at 3-, 9-, 15-, and 18-month
      intervals and tested in Rheometrics Solid Analyzer with nondestructive step
      strain loading to obtain a load deformation curve. Radiographs and histologic
      sections of each animal were compared. Peak force and force decay were analyzed
      by level and by age. Analysis of variance and Tukey's methods were applied to
      data. RESULTS: There were no statistically significant differences in
      biomechanical data. No histologic changes were noted in the study groups up to 18
      months of age. Radiographic differences characterized by subchondral bony
      sclerosis were noted by 18 months of age. No trends were noted when radiographic
      grades were compared with force data. CONCLUSIONS: The absence of biomechanical
      histologic changes in the intervertebral disc per se from 3 through 18 months,
      with radiographic changes in the subchondral bone, supports the hypothesis that
      the earliest changes in intervertebral disc disease in this animal model are
      related to the subchondral bone response.

PMID- 7809748
TI  - Elastin in the human posterior longitudinal ligament and spinal dura. A
      histologic and biochemical study.
AB  - STUDY DESIGN: A histologic and biochemical study of elastin in the posterior
      longitudinal ligament and spinal dura was performed using autopsy cadavers.
      OBJECTIVE: To provide a rationale for resiliency of the PLL and the spinal dura.
      SUMMARY OF BACKGROUND DATA: Among the spinal ligaments, the nuchal ligament and
      the ligamentum flavum have a very high elastin content, and some biochemical and
      morphologic studies of these ligaments have been published. No reports on the
      elastin content in the posterior longitudinal ligament or spinal dura have been
      published. METHODS: Specimens of the posterior longitudinal ligament and the dura
      collected from three cadavers were studied histologically. For quantitative
      analysis of elastin and collagen, the posterior longitudinal ligament specimens
      were collected from 22 cadavers and the dura specimens from 20 cadavers. Elastin
      was extracted using the hot alkali method of Lansing et al. RESULTS: The elastic
      fibers in the posterior longitudinal ligament generally were arranged parallel in
      the cephalocaudal direction, whereas the fibers in the spinal dura had a more
      multidirectional arrangement. The elastin content of the posterior longitudinal
      ligament averaged 7.3% of the total dry weight and that of the spinal dura was
      7.1% for the ventral aspect and 13.8% for the dorsal aspect. The elastin content
      of the spinal dura was about two times higher in all dorsal specimens than in the
      corresponding ventral specimens. The elastin content of the lower thoracic region
      was higher than that of any other region. The amino acid composition of the
      elastin in the posterior longitudinal ligament and spinal dura was similar to
      that previously determined in other spinal ligaments.

PMID- 7809749
TI  - Compression of brachial plexus as a diagnostic test of cervical cord lesion.
AB  - STUDY DESIGN: This study evaluated the clinical significance of radicular signs
      around the neck in relation to mechanical lesions of the cervical spine and cord.
      SUMMARY OF BACKGROUND DATA: Classical radicular signs around the neck, such as
      Jackson's sign or Spurling's sign, are not sensitive enough to detect
      corresponding lesions. OBJECTIVES: Compression of the brachial plexus elicits
      radiating pain (BP) in patients with cervical lesions. The clinical significance
      of this new sign as a potential indicator of the cervical lesion compared with
      other classical signs was evaluated. METHODS: Sixty-five patients who underwent
      magnetic resonance imaging of the cervical spine were prospectively evaluated for
      these clinical signs that elicit radiating pain around the neck. Clinical signs
      were correlated to deformity of the cervical spine and cord and to final
      diagnosis. RESULTS: Classical radicular signs often were lacking, even in
      patients with mechanical lesions around the cervical spine. However, BP was often
      observed in these patients. CONCLUSIONS: Compared with the classical radicular
      signs, BP is highly sensitive and reasonably specific in detecting mechanical
      lesions around the cervical spine, and suggests radicular involvement.

PMID- 7809750
TI  - Spinal cord intramedullary pressure. A possible factor in syrinx growth.
AB  - STUDY DESIGN: This study analyzed biomechanical characteristics of the cervical
      spinal cord, especially in relation to neck flexion. Intramedullary pressure was
      measured in different neck positions. OBJECTIVES: The results provided a
      rationale for dynamic changes in intramedullary pressure, with the flexed neck
      position playing a role in syrinx growth. SUMMARY OF BACKGROUND DATA: Dynamic
      changes in intramedullary pressure in the flexed position have been postulated to
      play an important role in syrinx growth. However, intramedullary pressure of the
      spinal cord has not been measured. METHODS: The authors designed a balloon method
      to assess, experimentally, intramedullary pressure dynamics of the spinal cord. A
      system was incorporated to examine the reliability of the balloons. Using 15
      mongrel dogs, two balloons were embedded in the cervical spinal cord.
      Intramedullary pressure of the spinal cord was measured in several neck
      positions. In 5 of them, the same measurements were repeated when the spinal cord
      and roots were transected. RESULTS: When filled with a suitable volume of water,
      the balloons faithfully transmitted the pressure of the environment. No pressure
      differences were observed with the neck in the extended or neutral positions.
      However, when the neck was flexed, intramedullary pressure significantly
      increased. This increase in intramedullary pressure in the flexed neck position
      was not observed after spinal cord and roots were transected. CONCLUSION: The
      results indicated that the intramedullary pressure of the cervical spinal cord
      increases when the neck is flexed. This phenomenon might play an important role
      in syrinx growth.

PMID- 7809751
TI  - The relationship between surface contour and vertebral body measures of upper
      spine curvature.
AB  - STUDY DESIGN: In this study, parameters of sagittal cervical posture obtained
      from surface markers and from vertebral body locations were compared. OBJECTIVES:
      Several postural parameters were examined to establish the degree to which
      surface measures of cervical alignment reflect the underlying vertebral body
      alignment. SUMMARY OF BACKGROUND DATA: Previous studies of the relation between
      surface and vertebral alignment in the thoracic and lumbar regions have shown
      conflicting results. Some data suggest a connection between surface cervical
      posture and head and neck pain, but the relation between surface and vertebral
      posture in the cervical region has not been reported. METHODS: Lateral view
      radiographs of 24 healthy volunteers were used to give the surface alignment of
      skin markers and the locations of the geometric centers of vertebral bodies.
      Three angles describing sagittal alignment were investigated: 1) forward
      inclination of C2 relative to C7 (cervical inclination); 2) cervicothoracic
      kyphosis; and 3) cervical lordosis. RESULTS: A strong relationship between
      surface and vertebral data was not established. Two factors were identified as
      contributing to the observed differences: length of spinous processes and depth
      of soft tissue overlying the spinous processes at each spinal level. CONCLUSIONS:
      The assumption that the surface curve is the same as the vertebral curve is not
      supported by these results, suggesting caution is needed in inferring vertebral
      alignment from observed surface contours.

PMID- 7809752
TI  - The relationship between intramuscular pressure of the paraspinal muscles and low
      back pain.
AB  - STUDY DESIGN: The relationship between lumbar intramuscular pressure and backache
      with degenerative lumbar spine diseases was examined. Lumbar intramuscular
      pressure in 102 patients with low back pain and in 20 normal adults was compared
      in different positions using Miller's microtip catheter transducer. OBJECTIVES:
      This study sought to study the relationship between intramuscular pressure of the
      lumbar back muscles and degenerative lumbar diseases. SUMMARY OF BACKGROUND DATA:
      Measurement of intramuscular pressure is an objective technique for diagnosing
      lumbar compartment syndrome. The diagnosis of chronic compartment syndrome of the
      lumbar back muscles is confirmed when an association between an increase in
      intramuscular pressure and the onset of back pain is established. As spinal
      alignment changes from lordosis to kyphosis, the intramuscular pressure increases
      and blood flow decreases. METHODS: Intramuscular pressure measurements of the
      lumbar back muscles were performed in various positions and loading. Results in
      patients with low back pain and in normal adults were compared. RESULTS: The
      intramuscular pressure levels were found to be closely related to position and
      loading. The pattern of changes in pressure depended on the type of disease. The
      changes in intramuscular pressure in the patients with backache were classified
      into four distinct patterns. Chronic compartment syndrome of the lumbar back
      muscles showed two pattern: waxing and plateau. CONCLUSIONS: Measurement of
      intramuscular pressure of the lumbar back muscles might be an important method of
      obtaining a greater knowledge about backache.

PMID- 7809753
TI  - Transfer of loads between lumbar tissues during the flexion-relaxation
      phenomenon.
AB  - STUDY DESIGN AND METHODS: This study used an anatomically detailed model of the
      lumbar tissues, driven from biologic signals of vertebral displacement and
      myoelectric signals, to estimate individual muscle and passive tissue force-time
      histories during the performance of the "flexion-relaxation" maneuver. Eight male
      university students performed three trials each of the "flexion-relaxation"
      maneuver with six pairs of surface myoelectric electrodes monitoring the right
      side of the trunk musculature, an electromagnetic device to record lumbar
      flexion, and videotape to record body segment displacement. OBJECTIVES: To
      examine the loads on individual tissues during the transfer of moment support
      responsibility from predominantly active muscle to predominantly passive tissue.
      SUMMARY OF BACKGROUND DATA: No previous studies, to the authors' knowledge, have
      examined individual tissue loading during the flexion-relaxation maneuver.
      RESULTS: Although most subjects were able to "relax" their lumbar extensors in
      full flexion, activity remained in the thoracic extensors and abdominals. Tissue
      load predictions suggested that while the lumbar extensor muscles were neurally
      "relaxed" (i.e., myoelectric silence), substantial elastic forces would assist
      the passive tissues in extensor moment support. On average, subjects sustained
      almost 3 kN in compressive load on the lumbar spine and about 755 N of anterior
      shear during full flexion with only 8 kg held in the hands. CONCLUSIONS: The
      "relaxation" of lumbar extensor muscles appeared to occur only in an electrical
      sense because they generated substantial force elastically through stretching.
      Loading of the interspinous and supraspinous ligaments, in particular, was high
      relative to their failure tolerance.

PMID- 7809754
TI  - The strength in anterior bending of lumbar intervertebral discs.
AB  - STUDY DESIGN: This was a motion segment experiment. OBJECTIVES: To determine the
      strength in bending of lumbar intervertebral discs. METHODS: Eighteen "motion
      segments" consisting of two vertebrae and the intervening disc and ligaments were
      loaded to simulate forward bending movements in life. The range of flexion and
      the resistance to bending of each specimen was compared before and after removal
      of the posterior elements. Nine of the discs were tested after the intradiscal
      pressure had been reduced by damaging the vertebral end plate in compression.
      RESULTS: The posterior elements restricted the disc to 80% of its full range of
      flexion. The strength in anterior bending of isolated discs decreased with age
      and was 33 Nm on average. Reducing intradiscal pressure did not affect the discs'
      strength in bending. CONCLUSIONS: Disc failure in bending occurs through
      overstretching of the outer anulus in the vertical direction. In life, the
      posterior elements may not adequately protect the posterior anulus from fatigue
      damage.

PMID- 7809755
TI  - Flexion-extension rhythm in the lumbosacral spine.
AB  - STUDY DESIGN AND OBJECTIVES: This study was conducted to depict the qualitative
      and quantitative changes of intervertebral rotation and translation from L1-L2 to
      L5-S1 during flexion, standing, and extension using dynamic lumbosacral
      radiographs. METHODS: A radiopaque ruler was placed on the back of each subject
      for the normalization of translational value. Eighty-nine volunteers were
      examined. RESULTS: From extension to flexion, all of the intervertebral rotations
      approached 0 degree from the lordotic position; the translations changed from
      slightly retro-listhetic to zero displacement. Using L3-L4 as a baseline for
      calculating the intervertebral differences in flexion, all of the rotational
      differences were less than 1.5 degrees, except at L5-S1, which remained 5
      degrees. The mean translational difference was less than 0.6 mm, except at L5-S1,
      where it remained 1.5 mm. CONCLUSIONS: The amount of total flexibility was level
      dependent and its frequency distribution is important. Qualitative rhythmic
      changes from extension to flexion and quantitative values of intervertebral
      difference in flexion help define the normal flexibility more accurately.

PMID- 7809756
TI  - Disc herniation with gas.
AB  - SUMMARY OF BACKGROUND DATA: Intradiscal gas is associated with tumors, infection,
      trauma, therapeutic and diagnostic spinal procedures, deposit illnesses, and disc
      degeneration. The existence of gas within the spinal canal has been seen on 17
      occasions, of which 13 were associated with discal hernias. METHODS: In this
      study, 19 additional patients with intraspinal gas corresponding to discal
      hernias are presented, six of whom required surgical treatment. The association
      of intraspinal gas with intradural hernias frequently is reported in the
      literature, although this has not been proven in our group. Intrahernial gas is
      associated with patients who have chronic problems and with advanced age.
      CONCLUSION: Intrahernial gas is much more common than is indicated in the
      literature. This finding often goes unnoticed, and the association between
      intradiscal gas and intradural hernias should be kept in mind.

PMID- 7809757
TI  - Gorham disease of the spine.
AB  - STUDY DESIGN: This is a case report of Gorham disease of the spine with review of
      the literature. OBJECTIVE: To review the diagnosis, therapy, clinical course, and
      prognosis of Gorham disease of the spine. SUMMARY OF BACKGROUND DATA: This is the
      17th reported case of spinal involvement by this rare type of idiopathic
      osteolysis. METHODS: The patient was studied with radiographs, nuclear bone
      scans, computed tomography scans, magnetic resonance scans, and biopsies. His
      spine was stabilized by posterior and anterior rods, corpectomies, and bone
      grafts. RESULTS: The patient's spine had remained stable for 22 months after
      surgery, but intractable chylothoraces and spreading bone destruction were
      present. CONCLUSIONS: Spinal Gorham disease has high morbidity and mortality, but
      the course in an individual patient is difficult to predict. Early spinal
      stabilization should be considered before irreversible neurologic complications
      occur.

PMID- 7809758
TI  - Post-laminectomy cerebrospinal fluid fistula treated with epidural blood patch.
AB  - OBJECTIVES AND SUMMARY OF BACKGROUND DATA: Cerebrospinal fluid fistula after
      spinal surgery is associated with a definite risk of meningitis or discitis, and
      as a result, early active intervention usually is recommended. METHODS AND
      RESULTS: This report describes the successful use of an epidural blood patch
      after a more conventional intervention--namely, surgical re-exploration--had
      failed to control a postoperative cerebrospinal fluid leak. CONCLUSIONS: The
      techniques involved in performing a blood patch after spinal surgery may well
      differ from those usually recommended in the management of spinal headache
      resulting from other causes of dural puncture.

PMID- 7809759
TI  - Aspergillus discitis with acute disc abscess.
AB  - STUDY DESIGN: Aspergillus osteomyelitis of the vertebral body and disc space is
      rare. This report discusses a case that occurred in an immunosuppressed 29-year
      old man and reviews the pertinent medical literature. OBJECTIVES: To review the
      management and treatment of Aspergillus osteomyelitis of the vertebral body and
      disc space. SUMMARY OF BACKGROUND DATA: The patient presented with acute
      neurologic compromise resulting from L5-S1 discitis and a large epidural soft
      tissue component secondary to the Aspergillus infection. RESULTS: The patient
      underwent aggressive surgical debridement along with treatment with amphotericin
      B and had a complete clinical recovery. CONCLUSIONS: The authors recommend a
      combined medical-surgical approach in most cases of vertebral Aspergillus
      osteomyelitis. Early surgery with vigorous surgical debridement along with
      antifungal treatment seems to yield a good outcome.

PMID- 7809760
TI  - Internal carotid artery thrombosis after cervical corpectomy.
AB  - SUMMARY OF BACKGROUND DATA: A 74-year-old man suffered an extensive right
      hemispheric infarct 72 hours after undergoing anterior corpectomies of the C4 and
      C5 vertebrae for cervical myelopathy resulting from ossification of the posterior
      longitudinal ligament. RESULTS: Angiography revealed proximal right internal
      carotid artery thrombosis with atherosclerosis and a normal left internal carotid
      artery. The thrombosis may have been due to stasis during lengthy retraction of
      an atherosclerotic carotid artery. CONCLUSIONS: Preoperative screening of
      internal carotid artery blood flow with Doppler ultrasonography is recommended
      before contemplating extensive anterior cervical surgery in middle-aged and
      elderly patients at significant risk for atherosclerotic disease.

PMID- 7809761
TI  - The natural history of disc herniation and the influence of intervention.
AB  - The natural history of lumbar disc herniation must be considered when evaluating
      the influence and outcome of intervention. The combination of clinical signs and
      symptoms and corresponding radiologic findings permits a more certain diagnostic
      conclusion compared with many other obscure back disorders. The relationship
      between low back pain and a herniated disc is unclear. Mechanical compression and
      chemical changes may be the source of nerve root symptoms. Studies have shown
      that the natural course of acute radiculopathy has a good prognosis. Bed rest,
      information, and analgesics usually are sufficient therapeutic measures.
      Prolongation of symptoms requires radiologic examination. The decision regarding
      continued conservative therapy versus surgical intervention must be evaluated.
      Chemonucleolysis and percutaneous nucleotomy are being used, but the indications
      are uncertain.

PMID- 7809762
TI  - Wilhelm Schulthess.

PMID- 7809763
TI  - Adjacent disc degeneration in patients with prior spinal fusion procedures.

PMID- 7809765
TI  - The crisis in South African family practice.

PMID- 7809764
TI  - Doctors and society--the Biko Lecture.

PMID- 7809766
TI  - Towards health for all South Africans.

PMID- 7809767
TI  - Statement on withholding and withdrawing life-sustaining therapy.

PMID- 7809768
TI  - Risk factors for coronary heart disease in the white community of Durban.
AB  - Coronary heart disease (CHD) is the leading cause of death among the white and
      Indian populations of Durban. This was a community-based study of the white
      population of Durban, which is predominantly English-speaking. There were 396
      subjects (194 men, 202 women) aged 15-69 years. A history of CHD was present in
      9.3% of the subjects. The important risk factors were hypercholesterolaemia,
      hypertension and smoking. The minor risk factors were obesity,
      hypertriglyceridaemia, hyperuricaemia, a sedentary occupation and a history of
      CHD in the immediate family. Electrocardiograph abnormalities denoting CHD were
      present in 17% of subjects. A study of the major risk factors showed that 35.1%
      (age and sex adjusted) had at least one major risk factor at the higher level
      (level A) and 33.8% (age and sex adjusted) at the lower risk levels (level B).
      When the combination of risk factors was taken into account, 15.2% and 28% had
      two major risk factors, one each at levels A and B respectively. On average the
      percentage of men and women with one risk factor or more increased with age. A
      protective high-density lipoprotein/total cholesterol ratio > or = 20% was
      present in 53.5% of the respondents. Because of the severe nature of CHD, an
      intensive programme for the primary prevention of CHD risk factors should be
      instituted.

PMID- 7809769
TI  - Increase in hospital admissions for acute childhood asthma in Cape Town, 1978
      1990.
AB  - To determine whether hospital admissions for acute childhood asthma were rising
      in Cape Town in line with the experience of other countries, Red Cross War
      Memorial Children's Hospital's records for the period 1978-1990 were analysed.
      These were compared with total admissions for non-surgical causes and lower
      respiratory tract illness as well as those for bronchiolitis and pneumonia.
      Asthma admissions showed a sharp upward trend from 1978 to 1984, a slower rise
      through 1987 and a levelling off since. The profile of hospital admissions for
      respiratory illness was also analysed. Black children were under-represented
      among asthma admissions compared with those for pneumonia. Asthma admissions
      occurred throughout the year but showed seasonal peaks in May and November.
      Reasons for these trends and patterns are discussed, as well as hypotheses for
      further research into the epidemiology of asthma in South Africa.

PMID- 7809770
TI  - Epidemiology of urethral stricture at Tygerberg Hospital.
AB  - Over a 12-month period, 120 consecutive male patients with confirmed urethral
      stricture were prospectively studied with regard to the epidemiology of the
      disease. Specific urethritis is the main aetiological factor (45%) and internal
      and external trauma account for an alarming 38.3% of cases. The prevalence is
      highest among 40-50-year-old coloured men who have had little schooling, multiple
      sexual partners and who have a low annual income. The incidence can be reduced by
      upliftment of moral and educational standards of the local population, and by
      emphasising the potential dangers of catheterisation and instrumentation of
      medical personnel.

PMID- 7809771
TI  - Notification of pesticide poisoning in the western Cape, 1987-1991.
AB  - There is a paucity of data on pesticide-related morbidity and mortality in South
      Africa. A review of notifications to the western Cape office of the Department of
      National Health and Population Development from 1987 to 1991 was undertaken to
      describe the epidemiological profile of pesticide poisoning in the region. Two
      hundred and twenty-five cases of pesticide poisoning were identified, of which
      the majority were from rural areas. Farmers, farm workers and their families were
      most frequently involved in poisoning events, which included accidents arising
      outside of workplace production (44%), self-inflicted injury (35%) and direct
      occupational contamination (11%). Farm pesticide stores were the most frequent
      source of pesticide and a seasonal variation in the trend of poisoning events
      could be discerned; this corresponded to agricultural spraying practices in the
      region. The mortality rate was significantly higher among those with self
      inflicted injury, particularly farm workers. A concurrent review of hospital
      admissions for 1991 found that 78% of cases had not been notified. In view of the
      key role of surveillance in reducing pesticide-related morbidity and mortality, a
      call is made to improve notification of pesticide poisoning so as to facilitate
      control of an important potential public health problem.

PMID- 7809772
TI  - Agrichemical safety practices on farms in the western Cape.
AB  - In order to study agrichemical safety practices in a rural farming area in the
      western Cape, an audit of 45 randomly sampled farms was performed over 3 months
      in 1992. A response rate of 87% was achieved, and the survey results suggest that
      approximately 9% of permanent and 14% of seasonal farm workers are employed in
      jobs with potential exposure to agrichemicals. While protective equipment was
      widely available, gloves and masks were seldom used, with little enforcement or
      commercial support from the suppliers of the equipment. Farm workers receive
      little training on pesticide safety, but interest in the possibility of further
      training for workers was high. In the absence of a system of pesticide disposal,
      the presence of residual, unwanted and outdated stocks of pesticides in farmers'
      stores, and to a lesser extent the presence of empty containers, are identified
      as important problems. Current pesticide storage practices require improvement by
      simple industrial hygiene measures. Health facilities available to workers on
      most farms are extremely limited, particularly in the light of statutory
      requirements for occupational safety and health under the Machinery and
      Occupational Safety Act. It is argued that collective solutions to problems of
      pesticide safety are possible within the ambit of a public health response,
      particularly given the willingness of the farming community to identify and
      address potential health problems. As a result, initiatives to meet these needs
      are currently under way in the region.

PMID- 7809773
TI  - The effects of a single treatment of an acaricide, Acarosan, and a detergent,
      Metsan, on Der p 1 allergen levels in the carpets and mattresses of asthmatic
      children.
AB  - Baseline levels of the house-dust mite allergen, Der p 1, were measured on the
      carpets and mattresses of 60 pure-mite-sensitive asthmatic children in the Cape
      Peninsula, by means of an enzyme-linked immunosorbent assay (ELISA). High levels
      of mite allergens were recorded (range 2-50 micrograms Der p 1/g dust). In order
      to investigate the efficacy of the application of acaricides to carpets and
      bedding, 3 groups of 20 children were studied. Carpets and mattresses in group A
      were treated with a detergent, Metsan (Snowchem), and in group B with Metsan
      combined with the acaricide, Acarosan (Noristan). Group C was a control group in
      which no treatment was applied. The level of airway hyperreactivity (PC20) to
      histamine was measured at the beginning of the study and again 3 months after
      acaricide treatment. Significant reductions in carpet Der p 1 levels were
      achieved in group A (22.83 v. 13.26 micrograms Der p 1/g dust; P = 0.04) and
      group B (21.76 v. 13.26 micrograms Der p 1/g dust; P = 0.01), but mite levels
      were not reduced in any of the mattresses treated. There was also no improvement
      in airway hyperreactivity in any of the groups. This study clearly demonstrates
      that at present it is not possible to reduce Der p 1 antigen levels in mattresses
      in the Cape Peninsula with the available acaricides, even when one of these is
      combined with a detergent solution. Until strategies are developed which will
      significantly reduce Der p 1 levels in the bedding of sensitive individuals, a
      reduction in ongoing airway inflammation and airway hyperreactivity cannot be
      expected.

PMID- 7809774
TI  - Drug allergy.
AB  - Drug allergy is an important complication in the use of agents such as
      penicillins, cephalosporins, sulphonamides, insulin and streptokinase. The
      allergenic properties of drugs are a function of molecular size and chemical
      reactivity. Factors determining an individual's risk of an allergic response are
      not fully understood but include genetic predisposition, prior exposure, route of
      administration, drug dosage, age and concomitant disease. The most dangerous but
      least common form of drug allergy is generalised anaphylaxis. The majority of
      reactions are non-anaphylactic and involve the skin, with a lesser incidence of
      haematological, renal, musculoskeletal, cardiorespiratory and other systemic
      manifestations. The only definitive test for allergy in a patient with a history
      of previous allergic reaction is rechallenge, a dangerous and seldom indicated
      procedure. An alternative is skin testing, but this requires an experienced
      practitioner and has intrinsic risk. In vitro testing may be of value in
      predicting the risk of rechallenge. Safe use of a suspect drug requires a careful
      assessment of risk and a cautious approach. Use of an offending drug in a high
      risk patient is rarely indicated, but if it is considered essential, initial
      therapy or desensitisation in an intensive care environment is recommended.

PMID- 7809775
TI  - South Africa needs a co-ordinated health manpower policy.

PMID- 7809778
TI  - Private ownership of firearms.

PMID- 7809776
TI  - [Private ownership of guns].

PMID- 7809777
TI  - [Private ownership of guns].

PMID- 7809779
TI  - [Dispensing - unfair treatment of doctors].

PMID- 7809780
TI  - Private ownership of firearms.

PMID- 7809781
TI  - Epidural block for postpartum sterilisation.

PMID- 7809782
TI  - Treatment of congenital syphilis.

PMID- 7809783
TI  - Wrist pain, steroid injections and tuberculosis.

PMID- 7809784
TI  - Congenital syphilis and STD surveillance.

PMID- 7809785
TI  - Medical costs of laparoscopic surgery--the most expensive hysterectomy.

PMID- 7809787
TI  - Laparoscopic hernioplasty in adults--are there any risks?

PMID- 7809786
TI  - The morbidity spectrum of specialist physicians in private practice.

PMID- 7809788
TI  - Pneumatocele diagnosis confirmed by computed tomography.

PMID- 7809789
TI  - Vaginal ultrasonography in the diagnosis of postmenopausal endometrial disease.

PMID- 7809790
TI  - Common childhood illnesses and HIV infection in Africa.

PMID- 7809791
TI  - An outbreak of type 1 dengue fever on Grande Comore island.

PMID- 7809792
TI  - Biological monitoring for organophosphate/carbamate pesticides--the
      cholinesterase assay.

PMID- 7809793
TI  - HIV testing in the insurance industry--the gap between theory and practice.

PMID- 7809794
TI  - Stress hormones in primates.

PMID- 7809795
TI  - Laparoscopic management of common bile duct stones.

PMID- 7809796
TI  - Laparoscopic management of common bile duct stones.

PMID- 7809797
TI  - Ultrasonography--the stethoscope of the surgeon in the era of endoscopic surgery.

PMID- 7809798
TI  - Halsted's nemesis. The common bile duct.

PMID- 7809799
TI  - Laparoscopic management of common bile duct stones. A multi-institutional SAGES
      study. Society of American Gastrointestinal Endoscopic Surgeons.
AB  - Laparoscopic common bile duct exploration (CBDE) was the subject of a multi
      institutional study on 226 patients from 19 major hospital centers. Female
      patients predominated (2.3:1); the average age was 54; 75% of cases were chronic,
      and the remainder were acute. Although 97% had preoperative ultrasonograms, only
      12% showed a stone in the dilated common bile duct. The alkaline phosphatase was
      elevated in 41% and the serum bilirubin in 28% of cases. Preoperative endoscopic
      retrograde cholangiography with sphincterotomy (ERC-ES) was performed in 8.5%;
      there was a successful stone extraction in less than half the cases.
      Cholangiography was performed in 99.5%, and in 94% of those cases, stones were
      found. In 83% of cases, stones were removed through the transcystic approach, and
      in 17% removal was throughout the CBD. In the majority of cases, the
      choledochoscope and wire basket (34%), irrigation (33%), or a combination of both
      was employed. In the transcystic group, 5% were converted to open procedures due
      to technical difficulty, as contrasted with the trans-CBD route, where the
      conversion rate was 19%. There were two ductal injuries. Minor complications
      occurred in 5.7% within 24 h; there was one death (0.4%). Within 30 days, the
      morbidity rate was 7% and there were no deaths. Retained stones were discovered
      in 2.6% of cases. Laparoscopic CBDE is a feasible approach for CBD stones which
      permits a definitive procedure in one stage, without pre- or postoperative ES. It
      is a skill which should be mastered by the biliary surgeon. Further improvement
      in instrumentation and technique should make the laparoscopic approach not only
      comparable but preferable to the standard open choledocholithotomy.

PMID- 7809800
TI  - Preliminary experience with intracorporeal laparoscopic ultrasonography using a
      sector scanning probe. A prospective comparison with intraoperative
      cholangiography in the detection of choledocholithiasis.
AB  - Laparoscopic ultrasonography is a novel technique which may be useful in
      screening for choledocholithiasis during laparoscopic cholecystectomy. Following
      concerns regarding the "learning curve" and accuracy associated with the adoption
      of this user-dependent technology, we have prospectively evaluated a commercially
      available 90 degrees sector scanning laparoscopic ultrasound probe during
      elective laparoscopic cholecystectomy. Laparoscopic ultrasonography was performed
      in 60 patients and identified common duct stones in nine patients (one "false
      positive" and "one false negative"), and previously unsuspected duct stones were
      defined in three out of four patients. The gallbladder and portal vein were
      constantly defined anatomical landmarks throughout the study, whereas the
      suprapancreatic bile duct, intrapancreatic bile duct, and pancreatic duct were
      identified in 100%, 80%, and 85% of patients in the third consecutive group of 20
      patients examined. Laparoscopic ultrasonography has the potential to accurately
      identify common duct stones during laparoscopic cholecystectomy and thereby
      implement a policy of "superselective" operative cholangiography. However,
      adequate training for surgeons unfamiliar with this technology is recommended.

PMID- 7809801
TI  - Common bile duct stones after laparoscopic cholecystectomy and its treatment. The
      role of ultrasound and intravenous and intraoperative cholangiography.
AB  - In the present work we recount our experience in handling common bile duct stones
      (CBDS) in our first 100 cases of laparoscopic cholecystectomy. In the first 50
      cases our diagnostic procedures involved the use of ultrasound exploration and
      intravenous cholangiotomography 48 h before laparoscopic surgery. We found three
      cases of residual CBDS. One of the cases was treated by means of ERCP. The other
      two cases were resolved by carrying out a transparietohepatic cholangiography
      after the ERCP procedure failed. After this experience, we changed our strategy,
      introducing the intraoperative cholangiography in the cases with an unclear
      diagnosis. With this new approach, no residual CBDS occurred in the following 50
      cases. These findings demonstrate the following: (1) In our hands, intravenous
      cholangiography is not more effective than ultrasound exploration in resolving
      dubious cases. (2) These dubious cases are more effectively diagnosed by means of
      selective intraoperative cholangiography. (3) When CBDS is treated by
      transparietohepatic cholangiography it proves to be less uncomfortable for the
      patient than ERCP and, as we found, even more efficient in removing the stones,
      although our experience is based on only two cases.

PMID- 7809802
TI  - Endoanal ultrasonography in the follow-up of anal carcinoma.
AB  - As the modern treatment for anal carcinoma is either radiotherapy alone or
      combined radiochemotherapy, an exact histological staging is impossible.
      Therefore we have to depend on an accurate preoperative staging method. Endoanal
      ultrasonography enables imaging of the normal anal canal and its pathologies. In
      a prospective investigation we were able to confirm the histological proven
      diagnosis of an anal epidermoid carcinoma in 12 patients with a 10-MHz transducer
      covered with a sonolucent plastic cone. The depth of infiltration can be
      determined in relation to the normal layers of the anal canal. Six patients
      treated with radiotherapy alone or combined radiochemotherapy were followed and
      the success or failure of the treatment was documented. Endosonography of the
      anal canal allows an exact staging of a primary anal carcinoma and the follow-up
      in irradiated carcinomas. Besides digital palpation and proctoscopy with biopsy,
      endosonography complements the preoperative staging of anal carcinomas.

PMID- 7809803
TI  - Biofragmentable anastomosis ring for laparoscopic bowel surgery.
AB  - Laparoscopic surgery is now being applied for colonic resection, and one of the
      key challenges is fashioning a sound anastomosis. The biofragmentable anastomosis
      ring, a modern version of the Murphy Button, has been utilized in a series of
      experiments to develop and evaluate laparoscopic anatomotic techniques. A series
      of purpose-built devices were used to fashion left and right simulated
      colectomies as well as for a variety of other anastomoses. Survival animal
      experiments were performed and demonstrate the feasibility of this technique.

PMID- 7809804
TI  - Laparoscopic colon surgery in a rat model. A preliminary report.
AB  - The effects of laparoscopic colectomy on immune function require further study.
      Because the rat has been widely used to investigate the immune system we studied
      the feasibility of laparoscopic sutured colon anastomoses in a rat model. We used
      a low-pressure CO2 pneumoperitoneum, a 2.7-mm 30 degree wide-angle arthroscope
      and video system, and microotologic forceps and scissors to perform two-handed
      dissection and suturing of the rat colon. The procedures included laparoscopic
      division of the colon and colostomy (group A, n = 3), laparoscopic closure of a
      colotomy (group B, n = 4), and complete laparoscopic division and reanastomosis
      of the colon (group C, n = 4). One anesthetic death occurred in group C. Necropsy
      performed 1-15 days postoperatively revealed no anastomotic leaks and two
      anastomotic strictures. Laparoscopic sutured colon anastomosis in the rat is
      feasible and may provide a new model for the physiologic study of laparoscopic
      colon surgery.

PMID- 7809805
TI  - Laparoscopic cholecystectomy in complicated cholelithiasis.
AB  - From January 1990 to December 1992, 129 patients presenting complicated
      cholelithiasis were included in a prospective study to assess the feasibility and
      efficiency of laparoscopic cholecystectomy. There were 84 females (65%) and 45
      males (35%). Mean age was 60 years (range from 23 to 88). There were 90 acute
      cholecystitis (70%), 14 empyema (11%), 14 cholecystitis on scleroatrophic
      gallbladder (11%), and 11 mucocele (9%) cases. Laparoscopic cholecystectomy has
      been successfully performed in 106 cases (82%) (group I). In this group of
      patients, morbidity and mortality were 4.7% and 0.9% (n = 1), respectively. Mean
      hospital stay was 4.7 days after uneventful postoperative course. Two patients
      required reoperation for complications (1.8%). Twenty-three patients (18%)
      required enforced conversion to laparotomy after unsuccessful laparoscopic
      procedure (group II). Mean hospital stay was significantly higher in group II
      (10.8 days, P = 0.0001). There was no difference between the two groups according
      to sex, previous surgery, or indications. Laparoscopic cholecystectomy may be
      attempted and successfully realized in complicated cholelithiasis without
      morbidity increase. Main advantages of this procedure are a shorter hospital stay
      and a better recovery period.

PMID- 7809806
TI  - Laparoscopic adhesiolysis.
AB  - The aim of this study was the detection of criteria that support the indication
      for laparoscopic adhesiolysis in patients presenting with unspecific symptoms. A
      prospective analysis investigates the value of laparoscopic adhesiolysis in
      patients with chronic abdominal pain after exclusion of other pathologic
      findings; 58 consecutive patients were followed after laparoscopic adhesiolysis.
      Endpoints of investigation were extent of adhesions, complications, postoperative
      hospitalization, and postoperative quality of life. A comparison was drawn to
      patients following laparoscopic cholecystectomy, laparoscopic cholecystectomy
      plus adhesiolysis, and conventional cholecystectomy. The results showed that
      major complications occurred in 10% of cases. In 45% of patients we found a
      complete remission, in 35% a substantial improvement, and in 20% a persistence of
      complaints. In a correlation between the preoperative complaints and the extent
      of adhesions we found small adhesions to cause recurrent abdominal pain without
      other symptoms while large adhesions produce recurrent abdominal pain in
      combination with symptoms indicative of intermittent bowel obstruction. Finally,
      the results of this study indicate a certain "ideal constellation" for an
      enduring successful adhesiolysis per laparoscopy: it is the subjective complaint
      of recurrent abdominal pain with a localized and reproducible punctum maximum in
      combination with a circumscribed area of adhesions at that site.

PMID- 7809807
TI  - Alternative laparoscopic management of perforated peptic ulcers.
AB  - Surgery--namely, suture closure-is still the treatment of choice for perforated
      peptic ulcers, despite the proven efficacy of Taylor's conservative approach.
      Such conservative management, however, has been proven less effective in high
      risk patients and those with perforations more than 12 h old. Here we suggest
      alternative laparoscopic treatments for perforated peptic ulcers. We have treated
      laparoscopically six patients (one F, five M; mean age 57.6 years; range 31-81
      years); the mean duration of the operation was 52 min; the median hospital stay
      was 7 days (6-15 days); H2-blockers, antibiotics, and fluids were administered in
      the p.o. course; the follow-ups range from 6 to 18 months. On the basis of our
      experience, the treatment of choice for perforated peptic ulcers is Taylor's
      conservative procedure and laparoscopic drainage of the abdominal cavity when
      there is mild peritoneal reaction (usually less than 6 h from the onset of
      perforation). In case of remarkable peritonitis (usually more than 12 h), it is
      mandatory to add an accurate lavage. When the site of perforation is concealed by
      the peritoneal inflammation it should not be searched; when visible, it might be
      obliterated with the round ligament or an omental tissue strand, particularly if
      larger than 1 cm in diameter.

PMID- 7809808
TI  - Surgical anatomy of the interior inguinal region. Consequences for laparoscopic
      hernia repair.
AB  - Exploration and placement of staplers in the internal inguinal region during
      laparoscopic hernia repair may sever blood vessels or nerves. Lesions of specific
      structures may be associated with such complications as hematomas and impaired
      sensibility in defined areas. Therefore, the course and topography of blood
      vessels and nerves in the preperitoneal tissue in this region were studied. Six
      human preserved male cadavers were dissected. Unsafe areas for stapling were
      described. An adjustment of the technique of laparoscopic hernia repair to
      circumvent these complications is proposed.

PMID- 7809809
TI  - Interleukin-6 and coagulation-fibrinolysis fluctuations after laparoscopic and
      conventional cholecystectomy.
AB  - This study assesses quantitatively the fluctuations of interleukin-6 (IL-6) and
      coagulation-fibrinolysis proteins in patients undergoing elective laparoscopic (n
      = 14) and conventional (n = 10) cholecystectomy. The patients in both groups were
      comparable in age and sex. Serum levels of interleukin-6, and plasma levels of
      fibrinogen, von Willebrand factor-antigen, tissue-type plasminogen activator
      antigen, and plasminogen activator inhibitor-1 were determined for up to 48 h
      postoperatively. The postoperative changes of all parameters tested were
      comparable in both patient groups with a trend toward a higher interleukin-6
      response at 8 h postincision (NS) and a trend toward a higher fibrinolysis
      inhibition (NS) after conventional cholecystectomy.

PMID- 7809811
TI  - Common hepatic artery pseudoaneurysm secondary to pancreatitis. Direct
      percutaneous embolization.
AB  - We report a patient with a common hepatic artery pseudoaneurism secondary to
      pancreatitis treated with direct percutaneous embolization as an alternative when
      transcatheter embolotherapy cannot be performed. Examination of the specimen
      revealed that the pseudoaneurism was completely trombosed with signs of
      embolization of its lumen.

PMID- 7809810
TI  - Perforation after endoscopic injection sclerotherapy for bleeding gastric
      varices.
AB  - Bleeding from gastric varices is an uncommon condition for which hemostatic
      control is difficult and ill defined. Most clinicians tend to achieve hemostasis
      by endoscopic treatment because of the prevailing poor general condition of these
      patients. A case of fundal perforation following excessive injection
      sclerotherapy is reported and possible mechanism discussed.

PMID- 7809812
TI  - ERCP and laparoscopic cholecystectomy for cholangitis in a 66-year-old male with
      situs inversus.
AB  - A case report of the successful management of a patient with situs inversus
      viscerum and symptomatic choledocholithiasis and cholangitis is presented. The
      preoperative evaluation of the choledochus via ERCP and successful common bile
      duct stone extraction enabled successful laparoscopic cholecystectomy. The
      anatomic challenge of situs inversus viscerum mandates the selective use of
      intraoperative cholangiography during and upon completion of the laparoscopic
      cholecystectomy.

PMID- 7809813
TI  - Transmural suture technique for trocar-site bleeding following laparoscopic
      cholecystectomy.
AB  - Laparoscopic cholecystectomy was performed in a cirrhotic patient who had
      cholelithiasis. Despite the existence of coagulopathy, excessive bleeding from
      the gallbladder and nodular liver was avoidable. Dissection and extraction of the
      gallbladder went smoothly. However, serious bleeding from the trocar site
      occurred following the withdrawal of the trocar/cannula. The bleeding was not
      controllable by electrocauterization. A novel attempt using a transmural suture
      technique was tried, and hemostasis was achieved satisfactorily. Our patient
      enjoyed an uneventful postoperative recovery and was discharged 2 days after
      surgery.

PMID- 7809815
TI  - Routine laparoscopic ultrasonography in biliary surgery. A preliminary
      experience.
AB  - A new technique of intraoperative imaging of the biliary tract in laparoscopic
      cholecystectomy is described. A specifically designed laparoscopic
      ultrasonographic probe is used to obtain both transverse and longitudinal views
      of the entire extrahepatic biliary tract. This technique was successfully used in
      28 patients. The ultrasonographic imaging quality achieved equals our experience
      with intraoperative ultrasonography in open biliary surgery. It may be assumed,
      therefore, that the advantages of ultrasonography over cholangiography as
      documented in conventional open surgery will also apply to laparoscopic
      operations.

PMID- 7809814
TI  - Metastatic implantation of an oral squamous-cell carcinoma at a percutaneous
      endoscopic gastrostomy site.
AB  - Percutaneous endoscopic gastrostomy (PEG) has become an important adjunct in the
      care of the head-and-neck cancer patient. When resection will likely affect
      swallowing, PEG can be performed just prior to cancer resection. However, it is
      unclear whether PEG should be the procedure of choice for establishing enteral
      access in head-and-neck cancer patients. In this report we describe a man with
      advanced oral squamous cell carcinoma who had a One-Step PEG button inserted
      immediately prior to his cancer resection. Six months later, the patient
      developed metastatic squamous-cell carcinoma at the PEG site. Although the
      mechanism of spread cannot be confirmed, direct seeding from passage through the
      cancer-filled oral cavity seems likely. Methods of establishing enteral access
      which avoid tumor-contaminated fields, such as use of an overtube during
      conventional PEG, open gastrostomy, or laparoscopic gastrostomy, may be more
      appropriate in head-and-neck cancer patients.

PMID- 7809816
TI  - A simple technique for thoracoscopic resection of lung tumors.
AB  - Mainly incited by the bushfirelike spread of endoscopic operative techniques in
      general surgery, thoracoscopy has become the object of new interest in the field
      of thoracic surgery. Location and resection of lung tumors are problematic for
      several reasons and so far not standardized. The main problems are pointed out. A
      new technique together with the instruments and their advantages is demonstrated.
      Future aspects are discussed.

PMID- 7809818
TI  - Endoscopic microlaparotomic esophagoplasty in the superior and posterior
      mediastinum with jejunal transplant.

PMID- 7809817
TI  - Slicer and tissue retrieval system for excisional endoscopic surgery.
AB  - Extraction of large specimens risks detachment of malignant cells within the
      peritoneal cavity and contamination of the parieties with resultant seedling
      implantation at the access wounds. Therefore, extraction is best conducted
      through a rip-proof sleeve-retrieval system which creates a "third space" in
      which the specimen can be sliced under visual control. Slicing of tissue is
      preferable to morcellation or disintegration since it preserves the structural
      integrity of the tissue and thereby does not jeopardize histopathological
      examination and staging of excised tumors. Of the two types of tissue-slicing
      mechanisms investigated, the compression-moving blade system (CMB) was found to
      be superior to wire-cutting devices. A prototype CMB slicer has been developed
      which has been tested experimentally and is currently undergoing clinical
      evaluation.

PMID- 7809819
TI  - A purse-string device for laparoscopic surgery.

PMID- 7809820
TI  - Perforation after endoscopic injection sclerotherapy for bleeding gastric
      varices. Surg Endosc 8: 1221-1222.

PMID- 7809821
TI  - Venous aneurysms: surgical indications and review of the literature.
AB  - BACKGROUND: During the last 20 years we diagnosed five cases of venous aneurysm
      of the jugular (n = 4) and basilic (n = 1) veins. The purpose of this report was
      to determine the natural history and indications for surgery of venous aneurysms.
      METHODS: Our five cases were included in an English-language literature review
      performed through August 1993. RESULTS: In our series two aneurysms (one external
      jugular vein, one basilic vein) were excised for cosmetic reasons. Three internal
      jugular vein aneurysms were followed up for up to 4 years without complications
      with serial color duplex ultrasonography. Of 32 patients with abdominal venous
      aneurysms (18 portal, seven inferior vena cava, four superior mesenteric, two
      splenic, one internal iliac), 13 (41%) had major complications including five
      deaths. Of 31 patients with deep venous aneurysms of the extremity (29 popliteal,
      two common femoral), 22 (71%) had deep vein thrombosis or pulmonary embolism and
      in 17 recurrent deep vein thrombosis or pulmonary embolism developed when
      patients were treated with anticoagulation alone. CONCLUSIONS: Prophylactic
      surgery is cautiously recommended for low-risk patients with venous aneurysms of
      the abdomen and strongly recommended for most patients with lower extremity deep
      venous aneurysms. Other venous aneurysms should be excised only if they are
      symptomatic, enlarging, or disfiguring.

PMID- 7809822
TI  - Integrin expression in primary breast cancer and its relation to axillary nodal
      status.
AB  - BACKGROUND: Integrins are transmembrane receptors that modulate cell adhesion.
      Each is a heterodimer of varying alpha and beta subunits. In malignancy, loss of
      integrin expression may result in less adhesive cells more likely to metastasize.
      Our aim was to characterize the integrins in human breast tissue and to examine
      the relationship between integrin expression and nodal metastasis in breast
      cancer. METHODS: Cryostat sections from 12 benign and 61 malignant (50 ductal and
      11 lobular) samples were stained by the avidin-biotin complex method with
      monoclonal antibodies to the beta 1, beta 3, beta 4, and beta 5 subfamilies. All
      slides were read by two independent assessors with consensus agreement. Integrin
      expression was compared to variables by using the chi-squared test with Yates'
      correction and multivariate analysis based on logistic regression. RESULTS: All
      integrin subunits studied were significantly reduced on breast cancer compared
      with benign cells (chi-squared test) but were not related to tumor
      differentiation. Loss of alpha 1 beta 1, alpha 2 beta 1, alpha 3 beta 1, alpha 6
      beta 1, alpha v beta 1, and alpha v beta 5 were related to the presence of
      axillary metastasis. Independently the integrins were of limited clinical value
      as predictors of axillary spread. However, on multivariate analysis the
      combination of beta 1, alpha v, alpha 1, tumor size, and vascular invasion gave a
      cumulative overall accuracy in predicting nodal disease of 97%. CONCLUSIONS:
      Integrin expression is reduced in breast cancer and may explain tumor
      progression. Measuring the integrins might thus provide a means of selection for
      aggressive axillary treatment.

PMID- 7809823
TI  - Bilateral obturator hernia: a new technique and a new prosthetic material for
      repair--case report and review of the literature.

PMID- 7809824
TI  - Laparoscopic adrenalectomy for Cushing's syndrome: comparison with primary
      aldosteronism.
AB  - BACKGROUND: Removal of adrenal adenoma of Cushing's syndrome is believed to be
      more troublesome than primary aldosteronism because of large amount of
      retroperitoneal adipose tissue and bleeding from the fat. The objective of the
      present study was to evaluate the feasibility of laparoscopic adrenalectomy for
      Cushing's syndrome and comparison of the results of laparoscopic adrenalectomy
      between primary aldosteronism and Cushing's syndrome. METHODS: From January 17,
      1992, to July 31, 1993, laparoscopic adrenalectomies for functioning adrenal
      lesions were performed in 14 patients (five men, nine women), three of whom had
      Cushing's syndrome and 11 of whom had primary aldosteronism. RESULTS: Operative
      times (mean +/- SD) for primary aldosteronism and Cushing's syndrome were 269.0
      +/- 100.9 minutes and 253.7 +/- 57.9 minutes, respectively. No difference was
      noted in operative time, operative bleeding, and postoperative recovery between
      them. However, the weight of removed tissue from patients with Cushing's syndrome
      (20.00 +/- 8.17 gm) was greater than that from those with primary aldosteronism
      (6.64 +/- 2.01 gm). No operative complications occurred in patients with
      Cushing's syndrome. Ultrasonic aspiration and argon-beam coagulation were useful
      for laparoscopic adrenalectomy in patients with Cushing's syndrome. CONCLUSIONS:
      Cushing's syndrome may be a good indication for laparoscopic operation.

PMID- 7809825
TI  - Thin-walled polytetrafluoroethylene graft failure is a cause of axillary pullout
      syndrome.

PMID- 7809826
TI  - Narrow margins of excision do not decrease survival.

PMID- 7809827
TI  - Increased serum lysozyme in the presence of abscesses.

PMID- 7809828
TI  - Isolated abdominal aortic dissection in a patient with Turner's syndrome.

PMID- 7809829
TI  - Postoperative salivary fistula: therapeutic action of octreotide.

PMID- 7809830
TI  - Port site seeding after laparoscopic ultrasonographic staging of pancreatic
      carcinoma.

PMID- 7809831
TI  - Neuromuscular recovery after parathyroidectomy in primary hyperparathyroidism.
AB  - BACKGROUND: Primary hyperparathyroidism today is diagnosed in the asymptomatic
      phase because of the inclusion of serum calcium in sequential multichannel
      analysis. The purpose of present study was to test for neuromuscular
      abnormalities in asymptomatic patients and to test the improvement of
      neuromuscular performance after parathyroidectomy. METHODS: Nine patients with
      primary hyperparathyroidism and nine patients with nodular goiter were enrolled
      in this study. Neuromuscular recovery including muscle power, sensation, and fine
      motor movement was studied before operation and 1 week and 4 weeks after
      operation. The muscle power was measured as grip power, palm pinch, lateral
      pinch, and three-chuck pinch. The sensation was measured as touch sensation and
      two-point discrimination. The fine motor movement was measured with the Purdue
      Pegboard Test and the Minnesota Manual Dexterity Test. RESULTS: Four weeks after
      the operation the patients with hyperparathyroidism had increased their muscle
      strength and had improved fine motor movement but no change was noted in two
      point and touch sensation. When the postoperative muscle recovery was compared,
      there was a reversible correlation (r = -0.62; p < 0.05) with the preoperative
      muscle strength and no correlation with the preoperative serum calcium,
      phosphate, alkaline phosphatase, and intact parathyroid hormone levels. No such
      improvement was detectable among the control subjects. CONCLUSIONS: Surgery can
      improve muscle strength and fine motor movement but does not affect sensation in
      asymptomatic patients.

PMID- 7809832
TI  - Efficacy of octreotide in the prevention of pancreatic fistula after elective
      pancreatic resections: a prospective, controlled, randomized clinical trial.
AB  - BACKGROUND: A prospective, randomized controlled clinical trial was conducted in
      33 Italian surgical departments with the aim of evaluating the efficacy of
      octreotide in the prevention of pancreatic fistula after elective pancreatic
      resections. METHODS: Between July 1990 and May 1992, 278 patients were enrolled
      in the study. Fifty-four dropped out because of unresectable disease and six were
      excluded because of protocol violation; the remaining 218 were randomly assigned
      to the octreotide group (n = 111) or to the placebo group (n = 107). There were
      131 men and 87 women with a mean age of 58.2 +/- 11.7 yrs.
      Pancreaticoduodenectomy was the most common operation performed (n = 143), sixty
      four percent of patients had a pancreatic or periampullary cancer; chronic
      pancreatitis accounted for 8.2% of cases. RESULTS: Mortality rate was 6.9%. A
      pancreatic fistula occurred in 31 patients (14.2%), 9% in the octreotide group
      and 19.6% in the placebo group (p < 0.05). Morbidity rate was significantly lower
      in the octreotide (21.6%) than in the placebo group (36.4%) (p < 0.05). When
      specific pancreatic complications were grouped together and evaluated, they
      occurred less frequently in the treated (15.3%) than in the placebo group (29.9%)
      (p < 0.05). CONCLUSIONS: Octreotide was able to reduce significantly the
      incidence of pancreatic fistula after elective pancreatic resections.

PMID- 7809833
TI  - Ductal dilatation and stenting make routine hepatectomy unnecessary for left
      hepatolithiasis with intrahepatic biliary stricture.
AB  - BACKGROUND: Hepatolithiasis with intrahepatic biliary strictures, more common in
      Southeast Asia than elsewhere, remains a difficult problem to manage. Hepatic
      resection has recently been advocated as one of the treatment modalities for
      hepatolithiasis; however, this procedure is not without risk. This study was
      designed to achieve complete clearance of the stones, eliminate bile stasis, and
      avoid the potential risks of hepatic resection in the patient with
      hepatolithiasis and intrahepatic biliary stricture. METHODS: In this prospective
      clinical trial 13 patients with retained left hepatolithiasis and intrahepatic
      biliary strictures were included. All the patients met the following criteria:
      (1) initial surgical procedure for hepatolithiasis, (2) normal gross findings of
      the left liver, and (3) no obvious clinical evidence of an associated
      intrahepatic cholangiocarcinoma. After the operation they underwent matured T
      tube tract ductal dilatation with percutaneous transhepatic cholangioscopy tube
      stenting. Choledochoscopic electrohydraulic lithotripsy was used in five patients
      after dilatation when impacted or large stones were encountered. RESULTS:
      Complete clearance of the stones was achieved in these 13 patients. One patient
      had fevers develop after ductal dilatation, and another patient had mild
      hemobilia after electrohydraulic lithotripsy. Both recovered uneventfully with
      conservative treatment. These successfully treated patients remain well, with a
      mean follow-up period of 20 months. CONCLUSIONS: Postoperative matured T-tube
      tract ductal dilatation and stenting, combined with endoscopic electrohydraulic
      lithotripsy when indicated, is an effective and safe alternative to hepatic
      resection for selected left hepatolithiasis with intrahepatic biliary stricture.

PMID- 7809834
TI  - Malignant islet cell tumor associated with hypercalcemia.
AB  - BACKGROUND: Three cases of islet cell tumors of the pancreas with hypercalcemia
      were studied, and 16 similar cases have been found in a 25-year review of the
      English-language literature. The purpose of the study was to review the cause of
      the hypercalcemia and the clinical characteristics of the tumors. METHODS: Tumor
      tissue retrieved from paraffin-embedded blocks was studied immunohistochemically
      for both parathyroid hormone (PTH) and PTH-related protein (PTHrP). PTH was
      measured in the serum in each patient and the serum PTHrP was measured by
      immunoassay in one patient. RESULTS: One of our patients had a fatal serum
      calcium level of 26.4 mg/dl. PTHrP stains were positive in two of our tumors, and
      one patient had an elevated PTHrP serum level. Serum PTH levels were normal or
      low in each patient. All three tumors were malignant and extremely vascular. The
      total group of 19 patients have in common hypercalcemia associated with a normal
      or low serum PTH level. Although the cause of hypercalcemia has not been proved,
      the tumors apparently produce PTHrP, because seven of eight tumors stained
      positive for PTHrP and each of the four patients tested had an elevated PTHrP
      serum titer. The tumors are extremely vascular, are usually malignant (17 of 18),
      and become large, but they are compatible with a relatively long patient survival
      time. CONCLUSIONS: These neuroendocrine tumors associated with hypercalcemia
      share several characteristics, but a claim that they represent another type of
      "functioning islet cell tumor" should await a clearer delineation of the cause of
      the hypercalcemia.

PMID- 7809835
TI  - Detailed characterization of experimental acute alcoholic pancreatitis.
AB  - BACKGROUND: With the ex vivo perfused canine pancreas preparation, the infusion
      of acetaldehyde, the primary metabolite of ethanol oxidation, plus a short period
      of ischemia to convert xanthine dehydrogenase to xanthine oxidase, results in the
      physiologic injury response of acute pancreatitis (edema, weight gain,
      hyperamylasemia). The free radical scavengers superoxide dismutase and catalase
      and a xanthine oxidase inhibitor, allopurinol, ameliorate this injury response,
      suggesting that toxic oxygen metabolites generated by xanthine oxidase play an
      intermediary role. METHODS: The isolated ex vivo canine pancreas preparation was
      perfused for 4 hours, and weight gain of the preparation and amylase activity in
      the perfusate were monitored. Changes in pancreatic acinar cell architecture were
      characterized by light and electron microscopy, and intracellular phosphate
      metabolism was followed by magnetic resonance spectroscopy in control
      preparations and in glands simulating alcoholic pancreatitis. RESULTS: Control
      preparations and preparations with a 1-hour period of ischemia before perfusion
      gained little weight (7 +/- 3 gm and 8 +/- 1 gm), amylase activity in the
      perfusate remained normal (933 +/- 513 units/dl and 1537 +/- 553 units/dl), and
      no changes in architecture were observed. Weight gain (5 +/- 6 gm) and amylase
      activity (1188 +/- 173 units/dl) were also normal in the preparations receiving
      acetaldehyde without preceding ischemia, but mild vascular and islet cell injury
      were observed on electron microscopy. One hour of ischemia followed by
      acetaldehyde infusion resulted in edema, increased weight gain (21 +/- 12 gm [p <
      0.05]), and amylase activity (2487 +/- 1484 units/dl [p < 0.05]). Microscopy
      showed mild acinar cell damage and greater injury to the capillaries and the
      islets. The capillary and islet cell changes were reduced by superoxide dismutase
      and catalase. Intracellular adenosine triphosphate levels remained at baseline
      levels in the control preparations. Adenosine triphosphate decreased during
      ischemia but quickly recovered during perfusion without a significant difference
      whether acetaldehyde was infused after ischemia. An iron chelator desferoxamine
      ameliorated the injury response in the preparations simulating acute pancreatitis
      (weight gain, 13 +/- 6 gm [p = 0.09] and amylase activity, 1198 +/- 471 units/dl
      [p = 0.08]), but a cholecystokinin receptor antagonist L364,718 did not have an
      effect. A sulfhydryl group protector, dithiothreitol, decreased weight gain (10
      +/- 7 gm [p = 0.06]), and amylase activity was not significantly increased over
      that of the control group (1582 +/- 641 units/dl), but a serine protease
      inhibitor phenylmethylsulphonylfluoride was ineffective. CONCLUSIONS: In this
      model simulating acute alcoholic pancreatitis, both the early physiologic injury
      response and the early morphologic changes are mediated at least in part by free
      radicals, which are generated by xanthine oxidase converted reversibly from
      xanthine dehydrogenase. In addition to the superoxide radical, the hydroxyl
      radical may also be an important early intermediate step, but the cholecystokinin
      receptor is not.

PMID- 7809836
TI  - Clinical significance of portal invasion by pancreatic head carcinoma.
AB  - BACKGROUND: The purpose of the present study was to clarify the indication of
      aggressive surgery for pancreatic head carcinoma. METHODS: Laparatomy was
      performed in 153 patients with carcinoma, 101 of whom underwent resection of the
      carcinoma. With histologic examination the degree of carcinoma invasion into the
      portal vein was classified into grades 0, I, or II according to the depth of
      invasion by the carcinoma. Macroscopic carcinoma invasion into portal vein was
      classified into types A, B, C, or D according to preoperative findings on the
      portal phase of superior mesenteric angiography or intraoperative portography.
      RESULTS: Macroscopic findings correlated with the histologic invasion grades. The
      1-year survival rate was 39.6% in grade 0, 11.3% in grade I, and 5.5% in grade II
      cases. The survival rates of patients with type A (p < 0.01), B (p < 0.05), and C
      invasion (p < 0.01) were higher than those of patients who did not undergo
      resection; however, no significant difference in the survival rates between
      patients who did not undergo resection and patients with type D invasion was
      observed. CONCLUSIONS: For locally advanced carcinoma of the pancreatic head or
      entire pancreas, patients with type D invasion have no indication of aggressive
      surgery.

PMID- 7809837
TI  - Effects of the antihypercalcemic drugs gallium nitrate and pamidronate on hormone
      release of pathologic human parathyroid cells.
AB  - BACKGROUND: Gallium nitrate and the bisphosphonates pamidronate and its
      dimethylated derivative comprise antihypercalcemic drugs with actions on bone.
      This study examines the in vitro effects of these compounds on human parathyroid
      cells. METHODS: Parathyroid hormone (PTH) release and the concentration of
      cytoplasmic calcium ion (Ca2+) of dispersed cells from parathyroid glands of 27
      patients with sporadic primary or uremic hyperparathyroidism was measured.
      RESULTS: In 1.25 mmol/L external Ca2+, 200 mumol/L gallium nitrate inhibited PTH
      release from preparations of primary and uremic hyperparathyroidism by 14% and
      22%, respectively. Similar reductions were evident also in 0.5 and 3.0 mmol/L
      Ca2+. The gallium nitrate-induced suppression of PTH release was dose dependent
      in the 2 to 200 mumol/L range. Cytoplasmic Ca2+ concentration displayed a
      biphasic rise on elevation of external Ca2+ and remained unaffected by gallium
      nitrate. None of the bisphosphonates altered PTH release of pathologic human or
      normal bovine parathyroid cells. CONCLUSIONS: The results support clinical
      usefulness of gallium nitrate through its dual actions on bone and the
      parathyroid. The findings substantiate that gallium may reduce PTH release by
      stabilization of the plasma membrane rather than by interference with the surface
      cation receptor mediating Ca2+ regulation of the secretion.

PMID- 7809838
TI  - Triglyceride-rich lipoproteins improve survival when given after endotoxin in
      rats.
AB  - BACKGROUND: Triglyceride-rich lipoproteins have been shown to bind bacterial
      endotoxin and inhibit its activity in vitro and to protect animals from death
      when administered before a lethal injection of endotoxin. We now demonstrate that
      triglyceride-rich lipoproteins can neutralize the toxic effects of endotoxin
      already in circulation. METHODS: Rats were infused with a lethal dose of
      endotoxin, followed at various time intervals by an infusion of either mesenteric
      lymph containing nascent chylomicrons (1 gm chylomicron triglyceride/kg) or an
      equal volume of normal saline solution. Survival was measured at 48 hours. The
      experiment was then repeated, substituting the synthetic triglyceride-rich lipid
      emulsion (1 gm/kg) for chylomicrons. We also measured the clearance and tissue
      distribution of radioiodinated endotoxin in rats treated subsequently with
      chylomicrons or saline solution. RESULTS: Chylomicron infusions significantly
      improved survival when given up to 30 minutes after a lethal dose of endotoxin (p
      < 0.05). Chylomicrons accelerated endotoxin clearance from the blood and
      increased endotoxin uptake by the liver. The synthetic triglyceride-rich lipid
      emulsion significantly improved survival when given up to 15 minutes after a
      lethal dose of endotoxin (p < 0.05). CONCLUSIONS: Triglyceride-rich lipoproteins
      and synthetic triglyceride-rich lipid emulsions significantly improve survival of
      rats when given after a lethal dose of endotoxin. Lipoprotein treatment
      accelerates endotoxin clearance to the liver, which may account for the observed
      protection. These data suggest a possible therapeutic role for triglyceride-rich
      lipoproteins or synthetic lipid emulsions in the treatment of the endotoxemia of
      gram-negative sepsis.

PMID- 7809839
TI  - Gastric and extragastric actions of the histamine antagonist ranitidine during
      posttraumatic sepsis.
AB  - BACKGROUND: Histamine H2 antagonists (e.g., ranitidine) are generally thought to
      specifically reduce gastric acid secretion and are commonly used for stress ulcer
      prophylaxis in critically ill patients because of their efficacy and safety
      profile. A few reports suggest that ranitidine might also bind to extragastric
      sites and/or act as an immunomodulator. The potential effects on posttraumatic
      sepsis are unknown. METHODS: Mongrel pigs (n = 24) were anesthetized with
      fentanyl, injured by a 10 kg steel bar dropped from a height of 1 m onto the
      fleshy portion of the posterior thigh, and then 35% of their blood volume was
      drained through the arterial catheter. All the shed blood plus two times the
      hemorrhage volume as lactated Ringer's solution was infused after a 1-hour shock
      period. Either vehicle or ranitidine (1.5 mg/kg) was intravenously administered
      at the time of resuscitation and every 12 hours thereafter in a blinded fashion.
      After 72 hours a septic challenge was administered (15 micrograms/kg Escherichia
      coli lipopolysaccharide [LPS] x 30 min). Serial gastroscopy, gastric pH,
      hemodynamics, leukocyte counts, cortisol, and tumor necrosis factor were recorded
      for 180 minutes after LPS. RESULTS: Immediately before LPS all hemodynamic
      variables were identical between treatments, but gastric pH was slightly higher
      and stress gastritis was marginally lower with ranitidine. LPS caused profound
      leukopenia and a hyperdynamic circulatory response (i.e., tachycardia, increased
      cardiac output, and decreased peripheral vascular resistance at relatively
      constant blood pressure); these changes were not altered by ranitidine. Gastric
      pH remained elevated after LPS with ranitidine, but LPS-induced gastritis was not
      modified. Ranitidine delayed the LPS-induced ventilation-perfusion imbalance and
      attenuated the peak increase in the proinflammatory cytokine, tumor necrosis
      factor, without altering its antiinflammatory opponent, cortisol. Similar changes
      were observed in four additional animals treated with cimetidine. The proportion
      of circulating neutrophils and lymphocytes was slightly altered 180 minutes after
      LPS, but there was no obvious effect on T lymphocytes in vivo, and no effect on
      the LPS-induced increase in neutrophil CD18 expression in vitro was seen.
      CONCLUSIONS: (1) Ranitidine increased gastric pH, which blunted the stress
      gastritis caused by trauma but not that caused by LPS; (2) ranitidine delayed the
      early LPS-evoked pulmonary changes and reduced the tumor necrosis factor spike,
      which is consistent with a favorable immunomodulatory action that has been
      reported in patients who are critically ill or are undergoing an elective
      abdominal surgical procedure; (3) the mechanism is probably related to H2
      receptor antagonism rather than to a nonspecific side effect of ranitidine, which
      suggests that histamine may have a previously unrecognized role in posttraumatic
      septic responses; and (4) the site of action is probably not in the heart or
      peripheral resistance vessels, but salutary effects on circulating lymphocytes or
      neutrophils cannot be excluded.

PMID- 7809840
TI  - A prospective randomized comparison of Dacron and polytetrafluoroethylene aortic
      bifurcation grafts.
AB  - BACKGROUND: The purpose of this study was to compare the long-term results of
      Dacron and polytetrafluoroethylene (PTFE) aortic bifurcation grafts in a
      prospective randomized manner. METHODS: Sixty patients with aortoiliac occlusive
      disease were randomized to receive Dacron or PTFE bifurcation grafts.
      Preoperative risk factors, perioperative blood loss and fluid requirements, and
      postoperative complications were compared. A mean follow-up of 57 months was
      achieved. RESULTS: The immediate postoperative morbidity and mortality rates were
      similar in the two groups, and the long-term complications were low in number and
      comparable. The cumulative patency rate for Dacron graft limbs was 86% versus 95%
      for PTFE graft limbs. CONCLUSIONS: No significant differences were noted between
      the results achieved with Dacron and PTFE aortic bifurcation grafts.

PMID- 7809842
TI  - Strategies for success in academic surgery.
AB  - BACKGROUND: A growing concern among university surgeons is a perceived threat to
      the traditional academician role. Factors that have led to this concern include
      (1) changes in reimbursement and patient referral patterns, both of which have
      resulted in reduced income; (2) mounting external pressure from the departmental
      chairperson/dean to generate professional fees; (3) pervasive ambiguity in the
      criteria for promotion and tenure; (4) intensified competition for research
      dollars in recent years; and (5) a perception that fellow academicians view
      surgeons as operating room technicians incapable of laboratory research. These
      cogent issues have the means to place academic goals in jeopardy. Potentially
      they lead to dissatisfaction, unhappiness, and eventual departure from academia.
      A healthy solution to the problem includes departmental recognition and reward
      for whichever primary role/s the academic surgeon embraces--clinical,
      educational, research, or administrative. Clear chairperson-faculty communication
      on the issues of expectation and reward is a key ingredient in the solution.
      METHODS: A mail survey was conducted with chairpersons of surgical departments
      and academic surgeons addressing the issues of retention, promotion, and
      benefits. RESULTS: Results revealed significant differences in perceptions,
      suggesting the need for improved communication between faculty and chairpersons
      and a team approach to help maintain academic viability in the future.
      CONCLUSIONS: When the quadruple threat can be mutually described as a
      departmental rather than individual quality, the joys and rewards of academic
      surgery can be considerable for faculty and chairpersons alike.

PMID- 7809841
TI  - Neutrophil adhesion receptor CD18 mediates remote but not localized acid
      aspiration injury.
AB  - BACKGROUND: Acid aspiration leads to lung polymorphonuclear neutrophil (PMN)
      sequestration and an associated increase in permeability. Although it is known
      that the neutrophil adhesion receptor (CD18) plays no role in determining PMN
      accumulations in the region aspirated, we postulated that this PMN adhesion
      receptor and its endothelial ligand, intercellular adhesion molecule-1 (ICAM-1),
      mediate remote neutrophil sequestration. METHODS: Anesthetized rabbits underwent
      localized aspiration of either 0.1N HCl 0.1 ml/kg (n = 18) or saline solution (n
      = 18). RESULTS: After 30 minutes leukopenia was noted, 2290 +/- 200 white blood
      cells/mm3 (p < 0.05). At 3 hours diapedesis occurred in the aspirated segment
      with accumulations in bronchoalveolar lavage fluid (X10(4)) of 87 +/- 6 PMN/ml
      versus control of 6 +/- 1 PMN/ml (p < 0.05). Histologic evidence of generalized
      lung leukosequestration occurred. The wet to dry weight ratio of the nonaspirated
      lung rose to 5.7 +/- 0.2 versus control of 3.9 +/- 0.1 (p < 0.05). Treatment (n =
      18) with the CD18 monoclonal antibody (mAb) (R15.7, 1 mg/kg) had no effect on
      neutrophil accumulations in the aspirated segment. However, the mAb attenuated
      the remote inflammatory response: early leukopenia (5790 +/- 400 white blood
      cells/mm3); lung leukosequestration (24 +/- 4 PMN/10 high-power fields); protein
      leak in bronchoalveolar lavage fluid (570 +/- 50 micrograms/ml); and edema, wet
      to dry weight ratio (4.9 +/- 0.1) (all p < 0.05). Treatment with the ICAM-1 mAb
      (RR1/1, 1 mg/kg) (n = 9) did not reduce neutrophil accumulations in the aspirated
      segment but limited the remote inflammatory response. CONCLUSIONS: Acid
      aspiration leads to neutrophil adhesion and edema in regions remote from those
      aspirated via neutrophil CD18 and endothelial ICAM-1.

PMID- 7809843
TI  - Detection of intraoperative tumor cell dissemination in patients with breast
      cancer by use of reverse transcription and polymerase chain reaction.
AB  - BACKGROUND: Animal studies have shown that malignant cells are shed into the
      blood stream during surgical resection of a primary tumor and that this may
      enhance the development of metastases. The evidence for tumor cell dissemination
      during surgical manipulation of human cancer is unclear. We have applied the
      technique of reverse transcription and polymerase chain reaction to detect
      circulating tumor cells in peripheral venous blood of patients with breast cancer
      perioperatively. METHODS: To target breast-specific gene transcription
      complementary DNA was prepared by reverse transcription of blood messenger RNA
      with oligonucleotide primers unique to CK18 and DF3 antigens. Preliminary
      assessment of specificity showed that the DF3 antigen was more suitable than CK18
      for the purpose of this study. Assessment of sensitivity showed that as few as 10
      tumor cells per 5 ml blood could be identified by this method. Peripheral blood
      samples were obtained by venepuncture from patients before, during, and 24 hours
      after breast surgery (nine malignant and three benign). RESULTS: In the group of
      patients with malignant disease, tumor cells were detected in one patient before
      operation and four patients during operation. No tumor cells were detected in the
      postoperative samples nor in any of the samples of patients with benign disease.
      CONCLUSIONS: These findings suggest that tumor manipulation during operation
      encourages tumor cell dissemination.

PMID- 7809845
TI  - [Torture--everybody should be educated].

PMID- 7809844
TI  - Ectopic eruption of the maxillary first permanent molar. An epidemiological,
      familial, aetiological and longitudinal clinical study.
AB  - The aims of this thesis were to investigate the prevalence, familial tendency and
      aetiological factors of ectopic eruption of the maxillary first permanent molar,
      to analyse associations between ectopic eruption of the maxillary first permanent
      molar, to analyse associations between ectopic eruption of the maxillary first
      permanent molar and other tooth and developmental disturbances and cleft lip
      and/or palate defects, to make a longitudinal evaluation of the effects of
      orthodontic treatment in irreversible cases and of the prognosis for the
      atypically resorbed second primary molars in cases of reversible ectopic eruption
      and to carry out histological studies of second primary molars with extensive
      resorptions. The thesis is based on eight investigations. The subjects for the
      prevalence study consisted of 2,903 children. The main subjects in the clinical
      studies were the children with ectopic eruption of the maxillary first permanent
      molar from those children. The methods used were radiographic assessments,
      biometrics, orthodontic treatment, histology, different statistical methods and
      clinical assessments. The prevalence of ectopic eruption of the maxillary first
      permanent molar was found to be 4.3 per cent for the population and 21.8 per cent
      for cleft children. In sibs to children with ectopic eruption the prevalence was
      19.8 per cent, indicating a genetic background. The main aetiological factors
      were the greater mesial angulation and the greater width of the ectopically
      erupted first permanent molar. In cases of reversible ectopic eruption the
      atypically resorbed second primary molars remained to the normal exfoliation time
      in 90 teeth out of 92. Treatment with cervical headgear in 46 children for an
      average of 9 months resulted in uprighting of the upper first permanent molars to
      good occlusion and in about 70 per cent of the children sufficient space for the
      second premolars. In the long-term follow-up, 10 years after treatment, two forms
      of discriminant analysis were used to evaluate the long-term treatment effects.
      The analyses showed a uniformity of the cases, indicating that the effects of the
      eruption disturbance had been corrected and all negative side effects of the
      treatment were eliminated.

PMID- 7809846
TI  - [Executive Board--the country's largest hospital system].

PMID- 7809848
TI  - [Joint management--control of equipment].

PMID- 7809847
TI  - [Executive Board--green light for employment of refugees].

PMID- 7809849
TI  - [Technology--PARRIS controls resources and quality].

PMID- 7809850
TI  - [Prevention--necessary with prohibition].

PMID- 7809851
TI  - [Prevention--we lack that quite concretely].

PMID- 7809852
TI  - [Prevention--Europe against cancer].

PMID- 7809853
TI  - [The wrong skin color].

PMID- 7809854
TI  - [Active research--doctorate for a practitioner. Interview by Grethe Kjaergaard].

PMID- 7809855
TI  - [Education--bridge-building].

PMID- 7809856
TI  - [Gap between theory and practice].

PMID- 7809857
TI  - [Relatives--the net consists of holes].

PMID- 7809858
TI  - [Leg support spares backs].

PMID- 7809859
TI  - [Education--untraditional examination].

PMID- 7809860
TI  - [Education--students like the forms].

PMID- 7809861
TI  - [WHO--health from the start of life].

PMID- 7809862
TI  - [Education--it takes time to provide a good study environment].

PMID- 7809863
TI  - [Nursing studies--difficult practice].

PMID- 7809864
TI  - [Medical education--still an education on treatment of human beings?].

PMID- 7809865
TI  - [Stoning in modern time].

PMID- 7809866
TI  - [When knowledge is not sufficient--on prescription of B-preparations].

PMID- 7809867
TI  - [Subarachnoid hemorrhage. Severe consequences of delayed diagnosis].
AB  - A total of 123 patients with subarachnoid haemorrhage were admitted to the
      Department of Neurosurgery, Haukeland Hospital, during the years 1990-93. In 16
      patients, there was a delay from the first haemorrhage until diagnosis and
      treatment. In eight patients, the delay was caused by incorrect medical
      diagnosis, while two patients did not seek medical attention immediately after
      onset of symptoms. In the remaining six patients, the delay was caused by both
      patient and physician. In all but one patient, the first symptom was an unusually
      severe acute headache which in some cases was accompanied by nausea and vomiting,
      in others not. Altogether nine patients suffered renewed bleeding, and three
      patients died. Three patients showed neurological impairment postoperatively. The
      article deals with the importance of early diagnosis in patients with
      subarachnoid bleeding, and suggests how these patients should be handled by their
      primary doctors and at the hospitals to which they are referred.

PMID- 7809868
TI  - [Hemolytic-uremic syndrome caused by verotoxin-producing Escherichia coli
      intestinal infection].
AB  - Enteric infections with verotoxin-producing Escherichia coli can progress to the
      haemolytic-uraemic syndrome. Several reports suggest that the incidence of
      verotoxin-producing E coli infections is increasing in the USA and Europe. Small
      epidemics of haemolytic-uraemic syndrome are usually traced to the ingestion of
      beef or dairy products. Epidemics of diarrhoea-associated haemolytic-uraemic
      syndrome have not yet been reported in Norway. We describe, for the first time in
      Norway, a sporadic case of haemolytic-uraemic syndrome that was associated with a
      verotoxin infection. Despite several life-threatening relapses the patient
      eventually made a good recovery after treatment with supportive therapy, plasma
      exchange, plasma infusions, corticosteroids, vincristine and ciprofloxacin. The
      authors stress the importance of continuing with intensive supportive therapy
      even when the prognosis seems hopeless.

PMID- 7809869
TI  - [Scurvy with simultaneous wet beriberi in 2 patients].
AB  - Two patients developed the clinical picture of scorbut and simultaneous wet
      beriberi. The diagnosis was confirmed by low concentrations of ascorbic acid and
      thiamin and thiaminfosfate-ester in serum and in whole blood. Treatment with
      ascorbic acid led to a rapid reversal of scorbutic changes, but the changes due
      to the wet beri-beri persisted. Thiamine supplementation was given only perorally
      in the first patient, and a severe catabolic state in the other delayed the
      improvement in the beriberi. Direct determination of ascorbic acid and thiamin
      and thiaminfosfate-esters in serum and in whole blood may confirm the diagnosis
      of vitamin deficiencies.

PMID- 7809870
TI  - [Chemical occupational environment of artists (painting, graphic, sculpture].
AB  - Visual artists are exposed to chemical irritants with a potential for reactions
      of the skin and mucous membranes. Such reactions are probably prevalent, and the
      professional and health consequences may be serious for persons with a low
      tolerance. Exposure to organic solvents may be high in silk screen printing and
      reinforced polyester casting. However, the risk of toxic encephalopathy requires
      exposure for several years. Lead and other heavy metals, plastic monomers and
      carcinogenic agents are used in several techniques. The health risk from these
      chemical agents is considered to be small, except among artists using special
      techniques and work routines. Changes in daily work routines seem to be most
      important way of reducing the occurrence of health effects among artists.

PMID- 7809872
TI  - [Aortoiliac arteriosclerosis treated with bypass surgery].
AB  - After introduction of the crimped Dacron bifurcation prosthesis, bypass surgery
      has been the preferred surgical treatment for arteriosclerosis in the
      aortoiliacal segment. During the years 1979-88 we performed 152
      aortoiliacal/femoral bypass operations. Perioperative mortality was 2%, while 96%
      of patients experienced improvement from operation. Primary and secondary five
      year graft patency rates were 84 and 88%. Considering the high risk in this
      patient group, we regard the operational mortality to be acceptable, and the long
      term results satisfactory. However, surgical treatment should be reserved for
      patients with serious occlusive disease in the aortoiliac segment. For patients
      with more limited lesions, endovascular procedures are a relevant alternative to
      surgery.

PMID- 7809871
TI  - [Ureteral obstruction and hydronephrosis. A complication after aortic bypass
      surgery].
AB  - Ureteral obstruction is a rarely reported complication of reconstructive surgery
      on the aorta. It is often an asymptomatic condition seen several years after the
      initial operation. The true incidence is unknown, but is estimated to 1%. As
      delayed hydronephrosis appears to be a marker of present graft complications, the
      patients should be closely evaluated. Two cases of ureteral obstruction are
      described and the management of this complication is discussed.

PMID- 7809873
TI  - [Femoropopliteal bypass in arteriosclerosis].
AB  - Since Kunlin's report on femoropopliteal bypass operations, this procedure, with
      homologous vein or various prosthesis has been the principal treatment for
      serious arteriosclerosis in this anatomical area. During the years 1979-88 we
      performed 235 femoropopliteal bypasses. Reversed autologous vein was used in 60%
      and the distal anastomosis placed below the knee in 75%. Perioperative, 30 days
      mortality was 2.1%. 93% of the operations were successful. The overall five year
      patency rate was 50.6%, but with significantly better results with the distal
      anastomosis above the knee. There was no significant difference, however, between
      reversed homologous vein and human umbilical vein grafts in the below knee
      position. At present, the indications for femoropopliteal bypass are critical
      ischemia and seriously incapacitating claudication.

PMID- 7809875
TI  - [Percutaneous transluminal angioplasty with stent in arteries of the lower
      extremity].
AB  - The application of intraluminal stents after dilatation of arterial stenoses and
      occlusions has proved to be a valuable addition to the armamentarium of
      radiological interventions. During the last two years we have applied 70 stents
      to 59 arterial lesions of the lower extremities in 45 patients. 57, or 96.6%, of
      the procedures were primarily successful, while two patients needed bypass
      surgery within 1-3 weeks. Follow up at 3-24 months showed that two stents were
      occluded 12-18 months after insertion, while intravenous digital substraction
      angiography showed the rest to be still open. We conclude that intravascular
      stenting improves the overall results of percutaneous transluminal angioplasty,
      and consequently expands the indications for this therapeutic procedure.

PMID- 7809874
TI  - [Percutaneous transluminal angioplasty in the treatment of arteriosclerosis of
      the lower extremities].
AB  - With the introduction of balloon catheters in 1974, dilatation of
      arteriosclerotic stenoses has become an important treatment for this condition.
      During the years 1979-88, 368 such procedures were performed in 270 patients. Two
      patients (0.7%) died from complications. In 8%, revascularisation was
      unsuccessful. Long occlusions appeared especially difficult to recanalize. 81% of
      the patients were improved by the treatment. The long term results were best in
      the iliac segment with 5-year patency of 90% after dilatation of short stenoses
      (< 4 cm) and 65% after dilatation of longer stenoses. In the femoropopliteal
      segment, the 5-year patency rates were 65% and 50% respectively. Results after
      recanalisation of occlusions were poor. Percutaneous transluminal angioplasty is
      an important supplement to surgery, applying mainly to patients with limited
      arteriosclerosis and moderate symptoms.

PMID- 7809876
TI  - [The physician-patient course in the medical education in Trondheim].
AB  - The new medical curriculum at the University of Trondheim is based on problem
      based learning in small groups and integrated teaching. An important element is
      the doctor-patient training programme run weekly during the two first years. This
      implies that, every other week, the students spend three hours in general
      practice. During the intervening week they spend three hours in a skills
      laboratory. The programme aims to train the students' communication skills in the
      doctor-patient relationship, to integrate basic sciences with clinical thinking
      and examinations, and to teach the students clinical skills. The programme
      enables the students to have early contact with patients, and provides them with
      personal supervision and support. 17 general practitioners serve as teachers in
      clinical practice, while specialists from most departments at the Faculty are
      involved as teachers at the skills laboratory.

PMID- 7809877
TI  - [Control of prescriptions of B-preparations. A registry study of B-preparations
      in Oslo and Akershus].
AB  - In two Norwegian counties all prescriptions for benzodiazepines and analgesics
      containing codeine were registered over a two month period and the records were
      subsequently transferred to a database. 93,000 prescriptions were registered,
      equivalent to this 2.8 millions DDD. The registration showed great variation,
      both in the doctors' volume of prescribing and their prescribing patterns. 30
      doctors of the total of 4,000 were responsible for 13% of the total volume
      prescribed. We propose that the doctors with unacceptable prescribing rates
      should be offered a special education program provided by the Norwegian Medical
      Association. The computer routines of the pharmacies appear to be inadequate for
      registration and research purposes. In 2% of all the prescriptions the doctors
      name could not be identified. Thus it seems warranted to use the doctors'
      identity number on prescriptions for these drugs. A reduction of the number of
      tablets in the largest packages dispensed should be considered by the
      authorities. For effective quality control of prescribing, better understanding
      is needed of the differences in doctors' prescribing patterns.

PMID- 7809878
TI  - [Time for realism].

PMID- 7809879
TI  - [Questionable guidelines on solid food to breast-fed infants].

PMID- 7809880
TI  - [Calprotect PhiCal ELISA--a current comment].

PMID- 7809881
TI  - [Certification by physicians and professional secrecy].

PMID- 7809882
TI  - [Severe invasive streptococcal infections].

PMID- 7809883
TI  - [Geriatrics--a specialty and organization].

PMID- 7809884
TI  - [Faster, higher, stronger--citius, altius, fortius].

PMID- 7809885
TI  - [Is top level athletic performance dangerous? A 25-year follow-up study of 24
      elite cross-country skiers].
AB  - In the years 1964-68, the Norwegian troop of elite cross-country skiers comprised
      27 skiers (15 men and 12 women). We present the results of a follow-up study 25
      years after the troop's active competing period. One of the male skiers died
      suddenly of acute myocardial infarction in 1986, one was unable to participate in
      the study because of other disease, and one female refused to participate. The
      follow-up study thus comprises 24 athletes (13 men and 11 women). The results
      show that the group has managed to keep in physically good condition after
      concluding the active period. Two of the participants had paroxystic atrial
      fibrillation. Apart from this no cardiovascular disease was found which could be
      attributed to the hard physical training as top athletes.

PMID- 7809886
TI  - [A general practitioner in a geriatric team. Experiences from a project at the
      Laerdal County Hospital].
AB  - At the local hospital in Laerdal a geriatric team has been established since May
      1991, and is organized as a project. Instead of a specialist in geriatrics the
      hospital has used a general practitioner with some geriatric experience and an
      interest in elderly patients. The team has also included a nurse, a
      physiotherapist and an occupational therapist. The services offered by the team
      have been well received by patients, general practitioners and other health
      workers in the region. It has now been decided that the team shall continue on a
      permanent basis from 1994.

PMID- 7809887
TI  - [Male infertility. Significance of life and occupation].
AB  - A retrospective study was carried out which focused on the impact of lifestyle
      and exposure to different external factors on sperm quality. A questionnaire was
      sent to 312 men who had previously attended our laboratory for semen analysis.
      Their answers were correlated to sperm quality. Men exposed to a relatively high
      degree of X-rays were found to have significantly reduced sperm count. A previous
      symptomatic genital infection did not significantly influence the sperm quality,
      but an earlier sexually transmitted disease in the female partner was associated
      with a reduced rate of pregnancy. Frequency of ejaculation was significantly
      positively correlated to sperm motility and inversely related to both semen
      volume and proportion of sperm with abnormal morphology. Information on exposure
      to the remaining factors was not related to reduced sperm quality or fertility.

PMID- 7809888
TI  - [Congenital fructose intolerance. New molecular aspects].
AB  - Hereditary fructose intolerance is a human autosomal recessive disease caused by
      a deficiency of aldolase B that results in an inability to metabolize fructose
      and related sugars. Molecular analyses have shown that most defects are caused by
      point mutations in critical regions of the aldolase B gene. We have performed PCR
      based DNA analysis of members of two Norwegian families with hereditary fructose
      intolerance. The affected individuals from both families contained a point
      mutation (A149P) in exon 5 of the aldolase B gene. Molecular diagnosis of
      fructose intolerance is rapid and specific, and causes no inconvenience to the
      patient. It should be preferred to conventional fructose intolerance tests and
      visceral biopsy analyses.

PMID- 7809889
TI  - [Depression fractures of the skull in newborn infants. Treatment with vacuum
      extractor].
AB  - Depressed skull fracture in newborns, usually called "ping-pong" lesion, is rare.
      The fractures may interfere with the function and growth of the brain and may
      establish an epileptogenic focus. Therefore early elevation is usually necessary.
      Traditionally, these lesions have been considered to be indication for
      neurosurgical elevation. During recent years, non-surgical elevation by means of
      breast pump or vacuum extractor have been reported. This procedure is technically
      feasible and less traumatic to the infant, and should be attempted before
      considering operative intervention. If the fractures are combined with bone
      fragments in the cerebral tissue or if epidural or subdural hematomas exist,
      surgical treatment is indicated. A case is described in which a depression
      fracture of the skull was successfully reduced by vacuum extractor.

PMID- 7809890
TI  - [Tumor marker analyses--valuable tools if used correctly].
AB  - The tumour marker assays in routine use today are not cancer-specific. Most
      markers are normal products of epithelial tissues, usually excreted from the
      intact organ. The infiltrating malignant growth allows release directly into
      lymph and blood, where the product is measured as a "tumour marker". Many tumour
      markers are glycoproteins depending on the liver function for their catabolism.
      These mechanisms explain the slight to moderate increases in tumour marker values
      found in various non-malignant diseases. Therefore, in general, such assays are
      of no use for screening healthy populations, and a normal value does not exclude
      cancer. Their main use is in the primary staging of patients known to have
      cancer, to evaluate the completeness of primary surgery, to follow-up patients
      for early detection of relapses, and to monitor the effect of cytotoxic or
      radiation therapy of advanced disease. In all these applications, good clinical
      judgement is the necessary basis for using these assays.

PMID- 7809891
TI  - [Adrenoleukodystrophy--clinical, biochemical and therapeutic aspects].
AB  - X-linked adrenoleukodystrophy is a metabolic disorder with broad clinical
      variations. The disease may be considered as a differential diagnosis in the case
      of encephalopathy, polyneuropathy, multiple sclerosis-like syndromes and adrenal
      insufficiency with unknown etiology. The most common form of adrenoleukodystrophy
      is lethal and starts with dementia in boys under ten years of age. The genetic
      defect is located to the Xq28 region and codes for a protein which regulates the
      transport of beta-oxidation enzymes in the peroxisomes. A defect of this protein
      seems to cause the accumulation of very long-chain fatty acids. This defect can
      be measured easily in the serum from patients and female carriers. Therapeutic
      attempts, for instance with Lorenzo's oil, in order to reduce serum level of very
      long-chain fatty acids, have not proven to be effective in already neurologically
      symptomatic patients. At present, the treatment of choice seems to be bone marrow
      transplantation in presymptomatic boys.

PMID- 7809892
TI  - [Percutaneous pleural and pericardial drainage].
AB  - Both MRI, CT and sonography will give a good presentation of fluid collection in
      pleura and pericardium. Sonography is the ideal imaging method for monitoring
      interventional procedures. Its ability to visualize superficial fluid collection
      and its real-time capability allows precise control of needle and catheter
      insertions. If the abnormality is poorly seen with ultrasound, often because of
      air in the collection, CT can be used as a guidance system. Diagnostic
      thoracocentesis and pericardiocentesis are performed mainly to exclude malignancy
      and infections, and the punctions are made with small needles. Therapeutic
      thoracocentesis is usually performed to relieve dyspnoea and small catheters are
      used. Drainage of empyema is performed with larger catheters because of the high
      viscosity of the infected fluid. Patients with threatening cardiac tamponade will
      often respond immediately to drainage of the pericardial space by catheter. These
      procedures can be done with local anesthesia only. If complications occur, it is
      mainly the pneumothorax that has to be treated. This can be managed directly
      under the procedure as the drainage catheter is attached to continuous pleural
      suction, or a catheter can be inserted in the pleural space after diagnostic
      punction. Patients with coagulation abnormalities must be evaluated especially
      before any intervention, otherwise there are no contraindications for these image
      guided percutaneous procedures.

PMID- 7809893
TI  - [Percutaneous drainage of abdominal abscesses].
AB  - Percutaneous drainage of abdominal abscesses has proved to be one of the most
      successful and gratifying of all interventional radiology procedures. Collections
      of intra-abdominal fluid can be detected easily with computer tomography and
      sonography. Diagnostic aspiration is done under guidance of sonography or
      computer tomography. Sonography is the ideal imaging method for monitoring
      interventional procedures. Its ability to visualize the collection of superficial
      fluid and its real-time capability allows precise control of insertions of
      needles and catheters. If the collection is poorly seen with sonography, often
      because of air, computer tomography can be used as a system of guidance. It is
      essential that radiologists and surgeons collaborate in the treatment of patients
      with abscesses. Percutaneous drainage is favoured in patients at high risk with
      open surgery, while diffuse collections between bowels almost always need
      surgical drainage. Simple abscesses can be treated successfully with percutaneous
      drainage. Complicated abscesses in the pancreas can also be treated with good
      results. The procedure is carried out under local anaesthesia. Most complications
      are minor and can be treated conservatively. Coagulation abnormalities must be
      corrected, but there are no other contraindications to these image-guided
      percutaneous procedures.

PMID- 7809894
TI  - [Practical teaching in occupational medicine. A good angle of approach in
      preventive medicine].
AB  - A new teaching programme in occupational medicine was established in Bergen in
      1991, as a joint project between the Institute of Occupational Medicine and
      several doctors engaged in occupational medicine in the Bergen area. The medical
      students, in groups of five, visit one of these company doctors for one day.
      During this day, they learn about the Occupational Health Care Unit, visit a
      company together with the doctor, and interview one employee. The education was
      evaluated by the students in 1992 and 1993. The comments from the students led to
      some changes in the programme. Student satisfaction was high, with a slight
      increase from 1992 to 1993. The programme led to increased enthusiasm for
      occupational medicine among the students.

PMID- 7809895
TI  - [WHO strategies to reduce childhood mortality in developing countries].
AB  - In 1990, world political leaders decided to make an effort to reduce childhood
      mortality in developing countries. One of several formulated goals was to reduce
      childhood mortality by one third compared with the figures for 1990. The child
      health programmes, which include vaccination, diarrhoeal and respiratory
      infection programmes, have already managed to reduce the mortality from common
      childhood diseases significantly. WHO is primarily an organization with technical
      cooperative aspirations, but still needs all possible available professional and
      economic support, in order to reduce childhood mortality even further.

PMID- 7809896
TI  - [Internet--a useful aid for physicians].

PMID- 7809897
TI  - [High-dose autologous stem cell administration in malignant diseases--an
      established method, unclear indications].

PMID- 7809898
TI  - [Are physicians going to lose their position and influence on medical research?].

PMID- 7809899
TI  - [Is blood pressure therapy as effective in the general population as in
      controlled trials?].

PMID- 7809900
TI  - [Marketing of inhalation steroids is more confusing than informative].

PMID- 7809901
TI  - Steps toward the new horizons of immunopathology continuing from the reach of my
      research career.

PMID- 7809902
TI  - Role of endogenous retroviruses in autoimmune diseases.
AB  - Retroviruses have been implicated in the pathogenesis of murine and human lupus;
      however, many positive findings have been followed by alternative explanations.
      Initial findings implicating xenotropic retroviruses were subsequently
      invalidated. The first solid demonstration that endogenous retroviruses mediate
      disease was the study of SL/Ni mice. Here budding ecotropic retroviral particles
      from arterial smooth muscle cells caused an antibody response to the particles
      with subsequent complement deposition. Our laboratory has focused on derangements
      in endogenous MCF retroviral expression. We found that lupus-prone NZB, BXSB and
      MRL strains have a marked increase in expression of Mpmv RNA in their thymuses
      while bone marrow expression did not differ from normal strains. Sequence
      analysis demonstrated mutations in the NZB endogenous retroviruses which could
      alter expression. A phosphorothioate antisense oligonucleotide to the initiation
      sequence of Mpmv caused lymphocyte activation in vivo in normal mice, providing
      further evidence for in vivo effects of Mpmv and potential for pathological
      abnormalities in lupus-prone strains.

PMID- 7809903
TI  - Lymphocyte membrane modifications induced by HIV infection.
AB  - Novel carbohydrate antigen expressions were observed on T lymphocytes from HIV
      infected patients using flowcytometric analysis with four mAbs; BM-1, ACFH-18, FH
      2 and C-6. These carbohydrate antigens were also expressed on oncogenic
      transformed cells but were either not expressed or were weakly expressed in
      lymphocyte populations from healthy subjects. A dramatic change in glycosylation
      was induced on CD8+T cells from HIV infected patients. The glycosylation change
      correlated with the progression of the disease. The incidence of Ley antigen
      expression on CD8+T cells increased as the disease progressed with the ongoing
      impairment of immune function. The phenotype change that occurred with Ley
      antigen expression might reflect the abnormal activation of T lymphocytes of some
      specific, but unknown, population of CD8+T cells. Thus, carbohydrate changes on
      the cell surface may induce immunological abnormality and accelerate the damage
      within the CD4+T cell subset, resulting in an impairment of the antigen specific
      immune system.

PMID- 7809904
TI  - Autoimmune diseases as stem cell disorders.
AB  - Using an animal model for insulin-dependent diabetes mellitus (IDDM), the NOD
      mouse, we have demonstrated that allogeneic bone marrow transplantation (BMT) has
      a preventative effect on IDDM, and that a combined transplantation of pancreas
      and bone marrow can be used to treat IDDM. We have also shown that BMT has a
      curative effect on systemic autoimmune disease in (NZB x NZW) F1, BXSB, and (NZW
      x BXSB) F1 mice but not in MRL/lpr mice. Since MRL/lpr mice possess abnormal
      radioresistant hemopoietic stem cells (HSCs), they suffer a relapse 5 months
      after BMT. Recently, we have found that major histocompatibility complex (MHC)
      matched stromal cells in the bone marrow are essential to the support of HSCs in
      the Go phase. We therefore attempted to treat autoimmune diseases in MRL/lpr mice
      by the transplantation of stromal cells with HSCs. Transplantation of HSCs with
      bone to recruit stromal cells was indeed found to have a curative effect on
      autoimmune diseases in the mice. These results indicate that BMT with bone graft
      will become a valuable strategy for the treatment of patients with both systemic
      and organ-specific autoimmune diseases. To prove that autoimmune diseases
      originate from defects in HSCs, we transferred the HSCs of autoimmune-prone mice
      to normal mice. BMT or transplantation of stem-cell concentrates induced organ
      specific and/or systemic autoimmune diseases in [NOD-->C3H/HeN] and [(NZW x
      BXSB)F1-->C3H/HeN or C57BL/6J] chimeric mice. These results provide direct
      evidence that the etiopathogenesis of autoimmune diseases, including both organ
      specific and systemic autoimmune diseases, is attributable to defects in the HSCs
      themselves. We further provide that various intractable diseases such as non
      insulin-dependent diabetes mellitus and chronic nephritis (focal
      glomerulosclerosis) are also organ-specific autoimmune diseases, and that BMT can
      be used to treat them.

PMID- 7809905
TI  - Molecular and cellular basis for pathogenicity of autoantibodies.
AB  - Using two different kinds of monoclonal autoantibodies, anti-mouse RBC (MRBC)
      autoantibodies and IgG3 rheumatoid factor (RF) cryoglobulins, we have attempted
      to better define the molecular and cellular basis of the pathogenicity of
      autoantibodies. Among eight anti-MRBC monoclonal antibodies (mAbs) obtained from
      NZB mice, only five of them are able to cause anemia. The distinct differences in
      specificity between pathogenic and non-pathogenic anti-MRBC mAbs emphasize the
      importance of autoantibody specificity for the pathogenesis of autoimmune
      hemolytic anemia. Histological examination has revealed that Fc gamma receptor
      mediated erythrophagocytosis and sequestration of agglutinated RBC in spleens and
      livers are the major pathogenic mechanisms of hemolytic anemia. This indicates
      that the affinity of autoantibodies for the Fc gamma receptors of phagocytes
      and/or the ability to cause hemagglutination, both of which vary among
      immunoglobulin isotypes, are additional factors determining the pathogenic
      activity of anti-MRBC autoantibodies. Studies on a panel of anti-IgG2a RF mAbs
      derived from MRL-lpr/lpr mice have demonstrated that only the IgG3 isotypes of RF
      mAb are able to generate cryoglobulins and to induce skin leukocytoclastic
      vasculitis and glomerulonephritis in normal mice. Although the cryoglobulin
      activity of RF mAb associated with the IgG3 isotype has been shown to be solely
      responsible for the generation of glomerular lesions (both RF and cryoglobulin
      activities are necessary for cutaneous vascular lesions), the absence of
      nephritogenic activity by some IgG3 monoclonal cryoglobulins supports the idea
      that qualitative features of cryoglobulins are critical to determine their
      pathogenic activities. Of interest, IgG3 autoantibodies lacking the cryoglobulin
      activity may not be harmful, but even protective against the development of IgG3
      cryoglobulin-mediated tissue lesions, because they inhibit the cryoglobulin
      formation of pathogenic IgG3 autoantibodies as a result of their nonspecific IgG3
      Fc-Fc interaction. Our results on monoclonal autoantibodies clearly indicate the
      importance of certain subpopulations of autoantibodies in the pathogenesis of
      autoantibody-mediated cellular and tissue injuries.

PMID- 7809906
TI  - Molecular analysis of the pathogenesis of autoimmune insulitis in NOD mice.
AB  - Among diabetes-susceptibility genes in NOD mice, only Idd-1 has been clearly
      assigned: Idd-1 could be a gene complex composed of class II major
      histocompatibility complex (MHC) genes, I-A beta and I-E. Employing restriction
      fragment length polymorphism (RFLP) analysis and nucleotide sequencing, we
      revealed that ILI and CTS mice, which are nondiabetic but are derived from the
      same Jcl-ICR mice as NOD mice, share the same class II MHC genes with NOD mice
      suggesting that both ILI and CTS mice also possess susceptible Idd-1 genotype.
      This was supported by a breeding study. To compare the usage of T cell receptor
      (TCR) V beta genes in NOD mice with that in ILI mice, we employed quantitative
      reverse-transcriptase polymerase chain reaction (RT-PCR) which revealed that TCR
      V beta usages of these mice were indistinguishable. RT-PCR method also revealed
      that the V beta transcript of T cells infiltrating into pancreas of NOD mice was
      not restricted but was rather diverse. Since NOD and ILI mice share the same
      class I and II MHC antigens, we performed lymphocyte transfer experiments between
      these mice to examine the mechanism by which ILI mice do not develop insulitis.
      The results of reciprocal transfer of lymphocytes from NOD to ILI-nu/nu mice or
      from ILI to young NOD mice suggest that ILI mice exhibit autoantigens responsible
      for the development of insulitis but do not possess T cells reacting with islets.
      Of the diabetes-susceptibility genes, only in the case of Idd-1 is there any
      evidence for the identity of the gene products. ILI mice should provide more
      information on the products of the other diabetes-susceptibility genes of NOD
      mice.

PMID- 7809907
TI  - Graft-versus-host reaction and GvH disease.
AB  - Chronic GvHR was induced by inoculating parental lymphoid cells into F1 hybrid
      mouse. Combination of ATL and ATH, which were congenic recombinant strains
      differing only in H-2I and S region from each other, was chosen to induce class
      II-GvHR. Selective activation against partner's alloantigen of graft CD4+ T cells
      was the primary event of the GvHR and then led to concomitant activation of both
      graft and host cells. Immune dysregulation among these cells made the GvHR-mouse
      express various chronic diseases including immune complex glomerulonephritis,
      autoimmune-like lesions of the liver or the salivary gland, tumor-like
      proliferations of T cells and abnormal extramedullary hematopoiesis. Chronic GvHR
      was also induced by a preferential but not a selective activation of graft CD4+ T
      cells. A combination of DBA/2 and C57BL/6, which differ in whole MHC antigens,
      was an example. When D2 cells, but not B6 cells, were incoulated into the BDF1
      mouse, predominant activation of CD4+ cells over CD8+ cells were observed.
      Contributing factors to this phenomenon were low responsiveness of graft CD8+ T
      cells to allogeneic class I MHC antigens and anti-parent activity of host CD8+
      cells. Thus both graft and host cells participate either actively or passively in
      the reaction induced in the parent --> F1 experimental system of GvHR/D.

PMID- 7809908
TI  - Role of endothelium in chronic inflammatory synovitis.
AB  - The rheumatoid synovial membrane is infiltrated by chronic inflammatory cells.
      The major fraction of the infiltrating lymphocytes is composed of CD4+ cells. A
      large number of studies of the composition of the T cell receptors of these
      lymphocytes have failed to demonstrate evidence of a dominant clonal population
      of T cells which is characteristic of rheumatoid synovitis. Most of the T cells
      are polyclonal in nature. This report discusses the basis for this polyclonality.
      Current evidence is reviewed which supports the conclusion that T cells emigrate
      from postcapillary venules because they are in an activated state. The activated
      T cell is characterized by elevated expression and avidity of adhesion receptors
      capable of reacting with counterreceptors on the endothelial cells of
      postcapillary venules, leading to binding and emigration from the blood. The T
      cells are retained in the perivascular connective tissue because their adhesion
      receptors interact with counterreceptors on other mononuclear cells and on matrix
      proteins. The increased expression of adhesion receptors on the T cells may be a
      result of prior contact with antigen; increased expression of counter-receptors
      on the endothelial cells results from stimulation by cytokines released by local
      inflammatory cells. The interaction between T cell adhesion molecules and
      counterreceptors is independent of the immunological specificity of the T cell.
      Hence, the T cells of the rheumatoid synovium are largely polyclonal memory
      cells.

PMID- 7809910
TI  - Nephritogenic antibodies in lupus nephritis.
AB  - A critical discussion of data on the possible role of IgG3 cryoglobulins, cross
      reactive anti-DNA antibodies and anti-DNA idiotypes in the pathogenesis of lupus
      nephritis is included. A further possibility involving cationic nuclear
      autoantigens is presented in detail. Histone was employed as a model antigen,
      representative of this group. Histones were shown to have high affinity for the
      rat GBM; they could also act as planted antigen and induce IC formation;
      furthermore they were able to mediate the binding of highly anionic DNA. The
      demonstration of histones in glomerular deposits in both lupus mice and patients
      with SLE is important evidence, linking such molecules with the kidney lesions.

PMID- 7809909
TI  - Osteoporosis in rheumatoid arthritis: a molecular biological aspect of connective
      tissue gene activation.
AB  - Osteoporosis, especially the juxtaarticular osteoporosis of involved joints, is a
      characteristic manifestation of rheumatoid arthritis (RA). Histomorphometric
      studies suggest the existence of increased bone turnover in RA: impaired bone
      formation and hightened osteoclasic bone resorption. Recent studies show that
      important mediators in the pathogenesis of RA such as prostaglandin E,
      interleukin 1 (IL1) or tumor necrosis factor (TNF) alpha also play important
      roles in bone remodelling. Prostaglandin E2 promotes maturation of osteoclasts
      from hematopoietic precursor cells. IL1 inhibits collagen synthesis in
      osteoblasts. IL1 enhances collagenase and stromelysin gene expression and
      stimulates osteoclastic bone resorption. TNF alpha inhibits bone collagen
      synthesis and causes osteoclastic bone resorption. TNF alpha, and possibly IL1,
      enhances collagenase and stromelysin gene expression by stimulating the AP-1
      promoter sites of the genes. Constitutive expression of c-fos induces joint
      destruction without lymphocyte infiltration in antigen-induced arthritis in mice,
      and supports cell growth of human rheumatoid synovial cells, possibly acting on
      the AP-1 sites. Furthermore, constitutive c-fos expression decreases collagen
      synthesis in osteoblasts and increases the mediator secretion from osteoblasts
      thereby stimulating osteoclastic bone resorption. These findings suggest that
      signal transduction through AP-1 transcriptional regulation sites may play an
      important role in the pathogenesis of joint destruction and osteoporosis in RA.

PMID- 7809911
TI  - Immunoglobulin variable-region structures in immunity and autoimmunity to DNA.
AB  - Important to the immunopathology associated with the autoimmune disease systemic
      lupus erythematosus, is the production of autoantibody to DNA. Crucial to
      understanding the immunological basis for autoimmunity to DNA is knowing whether
      the anti-DNA autoantibody is the product of clonally-selective, antigen-specific
      B cell stimulation or non-selective, polyclonal B cell activation. Structural
      analyses of the immunoglobulin variable-regions of both early, IgM and late, IgG
      anti-DNA antibodies from lupus-prone (NZB x NZW) F1 mice have indicated that both
      IgM and IgG anti-DNA autoantibodies are generated by clonally-selective B cell
      stimulation. Within individual autoimmune mice the later appearing, IgG anti-DNA
      autoantibodies are structurally similar to the earlier appearing, IgM antibodies,
      and in some cases both IgM and IgG may be produced by the same B cell clones. The
      variable-region structural data also suggest that DNA or complexes containing DNA
      may be the immunogenic stimuli for autoantibody to DNA. In support of this
      conclusion, normal mice immunized with immunogenic peptide-DNA complexes produce
      anti-DNA antibodies with structural and serological characteristics similar if
      not identical to those of autoimmune anti-DNA antibodies. Normal mice immunized
      with peptide-DNA complexes eventually develop immunopathology that resembles
      lupus nephritis. These results suggest that autoimmunity to DNA and subsequent
      autoimmune disease in SLE may result from a specific immune response to DNA
      containing antigens.

PMID- 7809912
TI  - Nephritogenic antibodies in MRL/lpr lupus mice: molecular characteristics in
      pathological and genetic aspects.
AB  - MRL/lpr mice spontaneously develop a lethal glomerulonephritis (GN). We found
      that IgG3 production in this strain of mice has a critical role on the
      development of GN; 1) IgG3 levels were high in kidney-extracted IgG and in
      circulating IgG immune complexes (IC), 2) serum IgG3 was selectively reduced by
      cyclosporin A treatment, associated with amelioration of GN, and 3) the mRNA
      levels of IgG3 correlated well with the severity of GN among the MRL/lpr x
      (MRL/lpr x C3H/lpr) F1 backcross mice with the rearranged genetic profile. Based
      on these results, we have successfully established five hybridoma clones which
      produce nephritogenic IgG3 antibodies from an unmanipulated MRL/lpr mouse. When
      they were injected to normal mice, four of the five clones generated cell
      proliferative GN associated with the marked cellular infiltrates, while the
      remaining clone induced wire loop-like lesions. This result suggests that
      particular antibodies generated in MRL/lpr mice have a different pathogenic
      potency. The V-region sequence study of these nephritogenic antibodies revealed
      that the two types of the glomerular lesions were mediated by a different B cell
      precursor. In conclusion, GN in MRL/lpr lupus mice is thought to be generated by
      the expansion of clonally different B cells producing nephritogenic antibodies
      with a different pathogenic potency.

PMID- 7809913
TI  - Endogenous retroviral envelope antigens recognized by B lymphocytes during graft
      versus-host reaction.
AB  - We recovered anti-murine retroviral hybridomas from the spleen cells of (B6 x D2)
      F1 mice in which graft-versus-host reaction (GVHR) had been induced by the
      infusion of spleen cells from either parent. The antibodies were specific for
      envelope proteins of endogenous retroviruses, and have provided a convenient way
      of classifying viruses based on their host range. They also have revealed
      considerable serologic heterogeneity within each host-range group. We have
      utilized these antibodies to characterize endogenous envelope glycoproteins in
      uninoculated mice. In this report I have attempted to synthesize the results of
      studies carried out by a number of senior investigators as well as postdoctoral
      fellows who have graced the Laboratory of Persistent Viral Diseases over the last
      10 years. Some of the information on the nature of the endogenous glycoproteins
      expressed within the hematopoietic compartment of DBA/2 and C57BL mice has
      provided a basis for speculation, offered at the end of the report, on the
      possibility that anti-retroviral autoantibodies generated during the course of
      GVHR may be antigen-driven.

PMID- 7809914
TI  - [Towards a policy for older workers?].

PMID- 7809915
TI  - [Judge and bones].

PMID- 7809916
TI  - [Incidence and prevalence of health problems in a group of nursing home patients
      with dementia. A comparison with family practice].
AB  - The objective of this study was to describe the health problems of a group
      dementia patients on admission and during residence in a Dutch nursing home and
      to compare these with figures of patients of 75 years and over from general
      practice. In 890 nursing home patients suffering from dementia prevalence of
      health problems on admission and the incidence during the residence were
      classified by means of the ICHPPC-2-defined. The differences between men and
      women were studied as was the influence of the season on the incidence during the
      stay. Results were compared with figures of patients of seventy five year and
      over from the continuous morbidity registration (CMR) from 'Nijmegen'. The most
      frequently occurring health problems on admission were: varicose veins of legs,
      acquired deformation of the spine, presbyacusis, hypertension, arthrosis, COPD,
      cerebrovascular disorders, heart murmur, cataract and chronic ischemic heart
      disease. During the residence the following health problems were frequently
      diagnosed: urinary tract infection, side effect of medicine, constipation,
      pneumonia, pressure sore, feeding problem, contusion, heart failure, cold and
      conjunctivitis. There were clear differences between men and women. Especially
      the incidence of intercurrent diseases showed great differences from the patterns
      in general practice. Prevalence of health problems on admission to the nursing
      home home agreed mor with figures from general practice. Respiratory tract
      infections frequently occurred in winter and urinary tract infections, pressure
      sores and conjunctivitis seemed to occur more in the summer. Nursing home
      patients with dementia have a lot of chronic and intercurrent health problems.
      They differ clearly from patients in general practice.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7809917
TI  - [Effect of physical activity in the elderly: a review of current literature and
      the possibility of economic evaluation].
AB  - The Netherlands government emphasizes the importance of preventive care for the
      elderly. From an economic and preventive point of view the potential of exercise
      programmes to reduce the use of health care services by the elderly deserves
      attention. We present an overview of the literature on the effects of physical
      activity on health and psychological well-being of the elderly and their use of
      health services. Our review covers the period 1988-1993 and also includes review
      articles. We found almost sixty relevant articles which about all satisfied our
      methodological criteria. In men, physical activity probably has a positive
      influence on the frequency of ischaemic heart disease. Exercise delays the onset
      of osteoporosis in women. The results for other diseases are ambiguous, despite
      the large amount of literature. Similarly, it is not clear yet whether physical
      activity can enhance well-being. Research on the effects of physical activity on
      the use of health services has hardly been done. We conclude that well-designed
      studies are needed to determine the cost-effectiveness of exercise programmes in
      the elderly.

PMID- 7809918
TI  - [Coping with loneliness: evaluation of a group course for elderly widows].
AB  - The present study was designed to evaluate a group course of 11 sessions, aimed
      at reducing loneliness in elderly widows. Twenty widows participated (mean age:
      67 yrs), who were all reasonably or very satisfied with the experience of
      participation as well as with the format and leadership of the course. At the
      beginning of the course, loneliness was a problem for each participant, and
      questionnaire scores for depression, well-being and social contacts (i.e.
      loneliness) were unfavourable. At the end of the course, one third of the
      participants indicated on an evaluation form that feelings of loneliness had
      become less intense. The corresponding questionnaire scores, however, did not
      improve significantly. However, rather large positive changes were found for
      depressive symptoms and for positive social support, which were maintained at a 3
      month follow-up measurement. The participants with higher depression scores were
      also the ones who showed the largest gain, although their scores remained in the
      pathological range. It is concluded that the latter participants suffer from more
      serious psychological problems than is desirable in view of the aims of the
      course. Adaptation of the aims and contents of the course should be considered,
      so that individual pathology can be more adequately addressed.

PMID- 7809919
TI  - Posttransplant diabetes mellitus--a review.

PMID- 7809920
TI  - Abrogation of baboon natural xenoantibody to pig splenocytes by DL-penicillamine.
AB  - Natural xenoantibodies are believed to be IgM in nature and are known to play a
      critical role in the hyperacute rejection of distantly related xenografts. The
      purpose of this study was to determine whether the reducing agent DL
      penicillamine could inactivate baboon natural xenoantibodies to pig splenocytes.
      Pooled baboon serum was treated with varying concentrations of DL-penicillamine
      over different lengths of time and a complement-mediated cytotoxicity assay was
      used to determine the reactivity of baboon natural xenoantibodies to pig
      splenocytes. A whole-cell ELISA assay was used to assess the binding of both IgG
      and IgM xenoantibodies to pig splenocytes. In addition, DL-penicillamine-treated
      serum was dialyzed to assess its potential clinical application. These in vitro
      experiments indicate that both IgM and IgG baboon natural xenoantibodies bind to
      pig splenocytes, but only IgM xenoantibody is cytotoxic. The binding of baboon
      natural IgM xenoantibody can be eliminated, and the cytotoxicity of IgM
      xenoantibody markedly reduced by DL-penicillamine treatment despite continued
      binding of IgG xenoantibody to pig splenocytes. In addition, DL-penicillamine can
      be dialyzed, suggesting that it may be an efficacious clinical treatment, the
      toxicity of which can be regulated with hemodialysis.

PMID- 7809921
TI  - Inhibition of leukotriene B4 synthesis does not prevent development of acute
      renal failure following storage and transplantation.
AB  - Compound BW B70C, a selective 5-lipoxygenase inhibitor was tested for its ability
      to reduce inflammatory damage in an in vivo rabbit model of renal storage and
      transplantation. Kidneys were stored at 0-2 degrees C for 48 hr prior to
      autografting. In controls, renal vein LTB4 levels rose significantly after 30 min
      reperfusion but fell after 2 hr to baseline. TxB2 levels remained at baseline for
      the 6 hr measured. 6-k-PGF1 alpha levels rose significantly after 1 hr of
      reperfusion and remained elevated thereafter. Histology after 6 hr reperfusion
      showed moderate-to-severe cortical edema and mild congestion. Infused colloidal
      carbon was retained in the perivascular area in a narrow band at the
      corticomedullary junction, indicating a zone of vascular permeability. At 3 days
      after transplant, kidneys exhibited widespread tubular necrosis and calcification
      but little inflammation. Serum creatinine and urea peaked between days 3 and 5.
      3/6 rabbits showed no symptoms of renal failure after 3 weeks. Pretreatment with
      BW B70C prevented the increase in LTB4 but had little effect on TxB2 and 6-k-PGF1
      alpha levels. Histology showed no amelioration of cortical edema at 6 hr and
      congestion and hemorrhage were exacerbated. BW B70C had no effect on either
      colloidal carbon retention or distribution but did significantly reduce tubular
      necrosis and calcification at day 3. There was very little inflammatory
      infiltrate. BW B70C treatment did not improve the long-term viability of
      transplanted kidneys: 2/6 rabbits showed no symptoms of renal failure after 3
      weeks. These data indicate that inhibition of LTB4 synthesis by BW B70C does not
      prevent the development of acute renal failure following 48 hr hypothermic
      storage and transplantation.

PMID- 7809922
TI  - The effects of administration of nitric oxide inhibitors during small bowel
      preservation and reperfusion.
AB  - The effects of nitric oxide (NO) during small bowel preservation and reperfusion
      were studied in a rat model of heterotopic, syngeneic LEW-->LEW transplantation.
      A 6-hr preservation interval was chosen, which leads consistently to moderate
      graft injury permitting graft and recipient survival. To evaluate the function of
      NO during preservation and reperfusion, two inhibitors (NitroG-L-arginine methyl
      ester [L-NAME] and NG-monomethyl-L-arginine [NMA]) were administered and compared
      with a transplanted group receiving no treatment. The extent of preservation and
      reperfusion injury were delineated by histologic study and by the measurement of
      mucosal glutaminase on tissue specimens obtained 20 min after revascularization
      and 24 hr and 4 weeks postoperatively. Serum and mucosal NO(2-)+NO3- levels were
      determined at the same time points. Graft function and survival was inferior in
      all cases where NO production was inhibited. When recipients were treated with NO
      inhibitors, graft function and survival was more impaired when L-NAME was
      administered compared with NMA administration. Donor and graft pretreatment with
      NO inhibitors impaired graft function but not survival, and was less detrimental
      than recipient treatment. Mucosal NO(2-)+NO3- levels significantly increased in
      untreated transplanted animals 20 min after reperfusion. This increase was
      abolished in groups treated with NO inhibitors. Serum NO(2-)+NO3- levels
      increased significantly after 24 hr, and this increase was even more pronounced
      when NO inhibitors were administered. Furthermore, liver function deteriorated
      after inhibition of NO, indicating a more severe inflammatory response of the
      recipient after NO inhibition. These data indicate that mucosal NO production
      within the graft during preservation, and especially during reperfusion, has
      beneficial effects, but increased serum NO(2-)+NO3- levels coincided with
      inferior graft condition due to preservation and reperfusion injury.

PMID- 7809923
TI  - Enhancement of endothelium-dependent contraction of the canine coronary artery by
      UW solution.
AB  - University of Wisconsin (UW) solution has been used almost routinely in the
      preservation of the hepatic, pancreatic, renal, and cardiac allografts. However,
      its effect on vascular endothelium is unknown. Experiments were designed to
      evaluate its effect on canine coronary endothelium. Canine coronary arteries (n =
      8 in each group) were preserved in cold (4 degrees C) UW solution (group 1) and
      physiological solution (group 2) for 6 hr immediately after harvesting. Segments
      of preserved and control (group 3) coronary arteries with or without endothelium
      were then suspended in organ chambers to measure isometric force. Perfusate
      hypoxia (pO2 30 +/- 5 mmHg) caused endothelium-dependent contraction in the
      arteries of all 3 groups. However, vascular segments with endothelium of group 1
      exhibited hypoxic contractions (107 +/- 26% of the initial tension contracted by
      prostaglandin F2 alpha 2 x 10(-6) mol/L, P < 0.05) that were significantly
      greater than those of the group 2 and group 3 segments with endothelium (25 +/-
      5% and 20 +/- 4%). The hypoxic contraction in arteries of group 1 could be
      attenuated by NG-monomethyl-L-arginine (L-NMMA), the blocker of endothelial cell
      synthesis of the nitric oxide from L-arginine. The action of L-NMMA could be
      reversed by L-arginine but not D-arginine. Endothelium-dependent relaxation of
      coronary endothelium to acetylcholine and adenosine diphosphate and endothelium
      independent relaxation and contraction of coronary smooth muscle were not altered
      by the UW solution. After preservation with the UW solution, endothelium
      dependent contraction of the canine coronary arteries, occurs by L-arginine
      dependent pathway, is enhanced. This augmentation by the UW solution would favor
      vasospasm after transplantation.

PMID- 7809924
TI  - Increased oxyradical production during reoxygenation of perfused rat liver.
      Signal versus injury.
AB  - Despite general agreement on the importance of oxyradicals in mediating
      "reperfusion" injury, the precise event(s) mediated by increased free radical
      production remain unclear. In this study we describe for the first time a model
      of unenhanced chemiluminescence of isolated perfused rat liver demonstrating a
      marked increase in oxyradical production after reoxygenation. Using aspartate
      aminotransferase and purine nucleoside phosphorylase release as measures of liver
      injury, there was no direct link between oxyradical production and hepatic
      injury. However, there was an abrupt increase in neutrophil chemotaxis activity
      in the perfusate at the time of reoxygenation with a subsequent decrement,
      following the pattern of oxyradical production. These data suggest that free
      radical formation during hepatic reperfusion may mediate signal transduction, as
      opposed to direct cell injury, as a primary mechanism of action.

PMID- 7809925
TI  - Detection of blood chimerism after lung and heart-lung transplantation. The
      superiority of nested as compared with standard polymerase chain reaction
      amplification.
AB  - Migration of donor cells from the graft to various tissues of the recipient has
      been demonstrated after different types of solid organ transplants. Currently,
      the detection of donor cells in the recipient's tissues is most simply performed
      by polymerase chain reaction (PCR) amplification of a donor-specific gene. In the
      present study, we first determined in vitro the sensitivity of standard and
      nested PCR amplification with sequence-specific primers (PCR-SSP) of a donor
      specific allele of the HLA-DRB1 gene and then used this technique to assess
      prospectively blood chimerism in two single-lung (SLT) and one heart-lung (HLT)
      transplant recipients. Standard PCR-SSP consisted in a single amplification round
      with sequence-specific primers for the donor-specific DRB1 allele. Nested PCR-SSP
      consisted in a first round of generic amplification of exon 2 of the DRB1 gene,
      followed by a second amplification round with primers specific for the donor
      allele. In vitro, nested PCR-SSP of the donor-specific allele was 1000-fold more
      sensitive than standard PCR-SSP and allowed the detection of 1 donor cell in
      10(5) recipient cells. In vivo, standard PCR-SSP detected donor cells among the
      recipients' peripheral blood mononuclear cells (PBMCs) only during the first
      postoperative days, whereas nested PCR-SSP demonstrated their presence until the
      end of the first postoperative month in patients 1 and 2 and until 3 months after
      transplantation in patient 3. We conclude that donor cells can be detected in the
      peripheral blood of SLT and HLT recipients during the first postoperative months
      and that nested PCR-SSP amplification of a donor-specific HLA-DRB1 allele is much
      more sensitive than standard PCR-SSP to demonstrate such chimerism.

PMID- 7809926
TI  - Different cellular patterns associated with hepatitis C virus reactivation,
      cytomegalovirus infection, and acute rejection in liver transplant patients
      monitored with transplant aspiration cytology.
AB  - Fine-needle aspiration biopsy (FNAB) is a routine diagnostic tool used for the
      monitoring of the graft during the first postoperative weeks after liver
      transplantation. The cellular pattern of acute liver rejection is typical in
      transplant aspiration cytology (TAC), documented and published by several
      authors. The lymphoid response associated with various viral infections may,
      however, provide differential diagnostic problems in the cytological monitoring.
      In this study, we have investigated in detail the cellular pattern of lymphoid
      response associated with hepatitis C virus (HCV) reactivation, and compared it
      with the pattern of cytomegalovirus (CMV) infection and with the typical
      diagnostic findings of acute cellular rejection. HCV reactivation was associated
      with rather mild total inflammation in the graft (4.5 +/- 1.5 CIU at the peak).
      The inflammatory infiltrate consisted mainly of small lymphocytes (3.1 +/- 0.2
      CIU at the peak), with only occasional activated cells and without lymphoid blast
      response. No lymphoid activation was seen in the blood. CMV infection was
      associated with a mild immune response (3.9 +/- 0.4 CIU at the peak) recorded as
      a slight lymphoid activation and occasional blast cells both in blood and in the
      graft together with lymphocytosis in the graft (2.4 +/- 0.7 CIU at the peak). The
      typical findings of acute rejection were easily distinguished from the cellular
      pictures of both viral infections. The rejections were lymphoid blast (3.6 +/-
      3.4 CIU at the peak) and activated lymphocyte (3.5 +/- 2.6 at the peak),
      dominated by a high peak of total inflammation (9.3 +/- 7.0 CIU). No blast cells
      and only a few activated cells were seen in the blood during rejection episodes.
      Thus, the cellular patterns of HCV reactivation and CMV infection differed
      slightly from each other, but significantly from that of acute liver allograft
      rejection monitored with the FNAB cytology.

PMID- 7809927
TI  - Serum alpha-glutathione S-transferase--a sensitive marker of hepatocellular
      damage associated with acute liver allograft rejection.
AB  - The wide hepatic distribution, high cytosolic concentration, and short in vivo
      plasma half-life of serum alpha-glutathione s-transferase are properties which
      may make monitoring this enzyme more clinically useful than conventional
      biochemical liver function tests as a marker of hepatocellular damage associated
      with acute liver allograft rejection. In a prospective longitudinal study of 58
      liver transplants in 45 patients, serum alpha-glutathione S-transferase
      concentrations rose significantly more consistently and more rapidly than
      conventional liver function tests in association with acute rejection. However, a
      rise in alpha-glutathione S-transferase was less specific for rejection than
      conventional liver function tests although none of the tests had a positive
      predictive value for rejection of greater than 32%. Compatible with the
      particularly short in vivo plasma half-life of this enzyme, alpha-glutathione S
      transferase concentrations fell to or toward normal more rapidly than
      conventional liver function test measurements following uncomplicated
      transplantation as well as during high-dose steroid treatment of rejection. This
      may be valuable, both in improving the resolution of biochemical changes
      associated with early rejection episodes and in determining when treatment of
      rejection has been successful. Further studies are warranted, however, to assess
      whether the fall in GST during rejection treatment does genuinely reflect the
      histological resolution of rejection.

PMID- 7809928
TI  - Plasma thrombomodulin in orthotopic liver transplantation.
AB  - Plasma thrombomodulin (TM), a specific marker of vascular endothelial injury was
      measured pre-, per-, and postoperatively in 16 consecutive patients undergoing
      orthotopic liver transplantation (OLT). The TM level, which was already elevated
      preoperatively, remained unchanged during OLT, except for an acute and transitory
      spike at the time of graft reperfusion. This TM peak is probably attributable to
      an acute release from the patient's endothelium because the TM level in the last
      saline rinse of the graft before implantation was low. This TM spike was not
      correlated with the progressive tissue-type plasminogen activator (t-PA)
      increase, plasminogen activator inhibitor 1 (PAI-1), or von Willebrand factor
      (vWF) values. The absence of accumulation of TM in plasma, unlike that of t-PA,
      suggests that the liver does not play a major role in TM clearance in humans. At
      the end of surgery, individual TM values returned to preoperative levels and
      remained unchanged during the 7 days following surgery. This observation suggests
      that the high (or very high) TM levels measured in these patients might be due to
      an indirect rather than a direct effect of liver dysfunction on the vascular
      endothelium which remained damaged during the postoperative period. The
      possibility that TM might be a predictive marker for thrombotic OLT complications
      remains to be investigated in a postoperative follow-up study.

PMID- 7809929
TI  - Increased antibody responsiveness to blood transfusions in pediatric patients.
AB  - Heightened immune responsiveness has been proposed as one of the reasons
      underlying suboptimal renal transplant results in very young children or African
      American recipients. Because multiple factors influence graft outcome, it has
      been difficult to provide experimental evidence to confirm or refute this
      suggestion. In the present study we measured IgG antibodies with confirmed HLA
      specificity produced in response to blood transfusions. The patients evaluated
      were renal transplant candidates who had not had previous pregnancies or
      transplants. The overall incidence of HLA sensitization was 12%. Age was the most
      influential factor in sensitization: patients < 20 years old were 4-5 times as
      likely to produce anti-HLA antibodies than patients > 20 (P = 0.0018). Female
      patients were also high responders. However, this was explained by the higher
      proportion of children among nulliparous female patients rather than by
      differences in gender. In contrast, the antibody response of black and white
      recipients was similar. The antibody levels in most patients were low and
      decreased significantly with time. We conclude that the immunoregulatory
      influences in patients < 20 years old favor the production of anti-HLA antibodies
      in response to blood transfusions, a fact that may explain some clinical
      observations in pediatric transplant recipients.

PMID- 7809930
TI  - Major histocompatibility complex class II expression is required for
      posttransplant immunological but not hemopoietic reconstitution in mice.
AB  - We had previously shown in a canine model that the administration of anti-MHC
      class II monoclonal antibody (MAB) immediately after autologous marrow
      transplantation prevented hemopoietic reconstitution. Since MHC class II
      expression in mice differs from that in dogs we were interested in determining
      the effect of MHC class II manipulation on posttransplant hemopoietic and
      immunological recovery in mice. Three murine models including MHC class II knock
      out mice were studied. BALB/c mice (I-E+, I-A+) given anti-MHC class II MAB H81.9
      (anti-I-E; 1 mg/kg/day, days 0-4) after TBI and infusion of syngeneic marrow or
      infused with anti-I-E purged marrow both showed normal hemopoietic
      reconstitution. Similarly, C57B1/6 mice (I-E-, I-A+) transplanted with M5/114
      (anti-I-A) purged marrow recovered normal hemopoiesis. MHC class II knock-out
      (C2D) mice, which lack class II completely, also recovered normal hemopoiesis
      after TBI and transplantation with either normal or class II-deficient (C2D)
      marrow, although the kinetics of platelet recovery as determined by
      megakaryocytopoiesis and platelet counts on day 14 were slightly delayed. C57B1/6
      mice transplanted with C2D marrow recovered normally. Immunologic recovery,
      however, was abnormal both in C2D recipients and in normal mice transplanted with
      C2D marrow: While CD8+ T lymphocytes recovered normally, no (or only very few)
      CD4+ T cells were identified posttransplant. Treatment of normal mice with anti
      MHC class II MAB in vivo or transplantation of MHC class II-purged marrow,
      however, did not interfere with complete immunological recovery, although T cell
      maturation was slightly delayed. Thus, complete immunological reconstitution
      requires the expression of MHC class II on marrow-derived precursor cells, while
      the expression of MHC class II antigens is not a requirement for hemopoietic
      reconstitution in mice.

PMID- 7809931
TI  - Sequential agonist activation and site-specific mediation of acute cyclosporine
      constriction in rat renal arterioles.
AB  - Evidence suggests that acute and chronic cyclosporine (CsA) nephropathy may be
      related to its renal vasoconstrictor effects. While the mechanism of CsA-induced
      renal vasoconstriction is uncertain, several studies indicate that endogenous
      constrictor agonists including endothelins (ET), platelet activating factor
      (PAF), and thromboxane A2 (TXA2) play a mediating role. In this study, two
      possible mechanisms explaining the participation of multiple constrictor agonists
      in CsA vasoconstriction were investigated: sequential activation of agonists
      initiated by CsA and site-specific mediation of CsA constriction by different
      agonists. The acute constrictor effects of CsA were examined in isolated rat
      renal afferent (AA) and efferent arterioles (EA) without and with specific
      receptor antagonists of ETA (BQ123, 10(-7) M), PAF (L-659,989, 10(-7) M), and
      TXA2/PGH2 (SQ29,548, 10(-7) M) in the bathing media. Both BQ123 and L-659,989
      completely inhibited CsA, constriction in AA, but had no significant inhibiting
      effect in EA. Constriction to ET-1 was also blocked by the PAF antagonist L
      659,989 in AA, but not EA. There was no effect of SQ29,548 on CsA constriction in
      AA--however, there was partial attenuation of CsA constriction in EA. Based on
      these results in isolated rat renal arterioles, it is suggested that CsA-induced
      constriction in AA is likely mediated by sequential activation of ET and PAF.
      However, CsA constriction of EA involves a different mechanism or mediator that,
      in part, may involve TXA2/PGH2 stimulation.

PMID- 7809932
TI  - IL-2 inhibits early increases in serum gamma interferon levels associated with
      graft-versus-host-disease.
AB  - We have recently demonstrated that a short course of high-dose IL-2 administered
      to lethally irradiated mice leads to marked protection from early and late GVHD
      mortality, especially when T cell-depleted (TCD) host-type bone marrow cells
      (BMC) are also administered. IL-2 inhibits the GVHD-inducing activity of donor
      CD4+ cells without inhibiting their graft-vs.-leukemia effects. Since CD4+ T
      lymphocytes produce a variety of cytokines, some of which have recently been
      implicated in the pathogenesis of GVHD, we have studied the possible effect of IL
      2 administration on serum levels of various cytokines. Acute GVHD was induced in
      lethally irradiated B10 mice by bone marrow transplantation (BMT) with MHC
      mismatched allogeneic (A/J) BMC and splenocytes. TCD B10 (host-type) BMC were
      coadministered to maximize the protective effect of IL-2. Serum cytokine levels
      were compared in recipients of these inocula with or without a protective course
      of IL-2 treatment. A marked increase in serum IFN-gamma levels was noted on days
      3 through 5 post-BMT in GVHD mice compared with syngeneic BMT control recipients.
      This GVHD-induced rise in serum IFN-gamma was markedly inhibited in IL-2
      protected mice. Murine IL-2 levels were only slightly increased in sera of GVHD
      mice, and were not influenced by treatment with human recombinant IL-2. Serum
      levels of the monokines TNF-alpha and IL-1 alpha showed variable early elevations
      in GVHD mice with or without IL-2 treatment, and were not different from levels
      observed in syngeneic controls. Serum levels of IFN-gamma, IL-1 alpha, and TNF
      alpha all declined markedly by day 7 to 8 post-BMT, when GVHD mortality begins.
      Administration of neutralizing anti-IFN-gamma mAb did not attenuate and tended to
      accelerate GVHD mortality, and administration of exogenous IFN-gamma did not
      overcome the protective effect of IL-2 against GVHD. Together, our results
      indicate that GVHD is associated with high serum levels of several
      proinflammatory cytokines in the first week post-BMT, but that these levels
      decline by the time when GVHD mortality begins. IL-2 specifically inhibits the
      GVHD-associated production of IFN-gamma, but this inhibition in itself does not
      explain and may even mitigate the protective effect of IL-2 against early GVHD
      mortality. However, the demonstration that IL-2 markedly inhibits the production
      of a GVHD-associated cytokine raises the possibility that alterations in the
      production of as yet undefined cytokines may be responsible for IL-2-induced GVHD
      protection.

PMID- 7809933
TI  - Tumor necrosis factor-alpha and interleukin-6 production induced by variations of
      DR4 polymorphism during the primary mixed lymphocyte reaction.
AB  - Serologically defined MHC class II differences provoke release of TNF-alpha and
      IL-6 during MLR. In order to assess the influence of micropolymorphism defined at
      the genomic level, we selected informative donors pairs within DR2 DR4
      serologically defined unrelated subjects by combining those differing only by DR4
      alleles, as assessed by PCR-SSOP (DRB1*0401 to 07). Two groups of MLR
      combinations were tested including DRB1-identical (group 1, n = 12) and one DRB1
      difference (group 2, n = 16). Pairs of HLA-identical siblings (n = 4) and of
      unrelated subjects differing by two major DR incompatibilities detected by
      serology (n = 27) were used as controls. We further investigated whether DP and
      DQ differences contributed to the observed CK production. Comparison of group 2
      with group 1 showed that one DRB1 difference had a marked influence on CK
      production at day 3 (TNF-alpha: 401.8 +/- 85 pg/ml vs. 128.7 +/- 34.5 pg/ml, P =
      0.001; SI = 2.97 +/- 0.23 vs. 1.27 +/- 0.09, P < 0.0001; IL-6: 317.6 +/- 44.8
      pg/ml vs. 108 +/- 13 pg/ml, P = 0.003; SI = 2.53 +/- 0.37 vs. 1.11 +/- 0.05, P <
      0.0001). However, CK release in group 2 was significantly lower than that
      observed in subjects with two serologically defined DR differences (TNF-alpha:
      515.1 +/- 61.4 pg/ml, P = 0.05; SI = 5.61 +/- 0.48, P < 0.0001; IL-6: 545.9 +/-
      75.8 pg/ml, P = 0.03; SI = 4.75 +/- 0.58, P < 0.0004). Addition of LPS after one
      day of MLR resulted in discriminant production of CK in group 2 as compared with
      group 1. Neither DP nor DQ differences affected CK production. In conclusion, DR
      subtypic differences induce significant CK release during primary MLR. This in
      vitro study demonstrates the immunodominance of the DR system in eliciting strong
      inflammatory mediators release.

PMID- 7809934
TI  - Beating neonatal rat cardiomyocytes as a model to study the role of xenoreactive
      natural antibodies in xenotransplantation.
AB  - The hyperacute rejection reaction of xenogeneic organs is supposed to be
      triggered by xenoreactive natural antibodies of the recipient organism. In an
      experimental set-up allowing for rapid medium exchange, primary cultures of
      spontaneously beating neonatal rat cardiomyocytes were challenged with dialyzed
      human serum containing xenoreactive natural antibodies. After adding the serum
      specimens, a reproducible pattern of disturbed contractility was observed:
      following an initial increase in beating frequency, spontaneous contractions
      stopped completely. This standstill was reversible in all experiments. No signs
      of permanent cytotoxicity were observed. The temporary cessation of contractions
      was prevented by raising extracellular calcium concentration, but not by
      extracellular electrical stimulation. After absorption of xenoreactive natural
      antibodies, cellular contractions ensued without interruption. Inactivated serum
      specimens produced similar effects on contractility, although the duration of the
      standstill period was significantly shorter. The same qualitative phenomenon
      occurred when sera of other xenogeneic species were used. These results point to
      a temporary functional disturbance of parenchymal cells by xenoreactive natural
      antibodies, whereas no chronic cytotoxicity was conspicuous in these experiments.

PMID- 7809935
TI  - Long-term results with elective cyclosporine withdrawal at three months after
      renal transplantation--appropriate for living-related transplants.

PMID- 7809936
TI  - The arterial ketone body ratio in living-related donors.

PMID- 7809937
TI  - Renal transplantation without immunosuppression in a host with tolerance induced
      by allogeneic bone marrow transplantation.

PMID- 7809939
TI  - Cultured endothelium. Heparin antagonizes the induction of class II MHC molecules
      by interferon-gamma.

PMID- 7809938
TI  - The role of T cell subsets in regulating the in vivo efficacy of CTLA4-Ig in
      preventing graft-versus-host disease in recipients of fully MHC or multiple minor
      histocompatibility-disparate donor inocula.

PMID- 7809940
TI  - Selection bias in multiple clinical protocols.

PMID- 7809941
TI  - Morphogens dropping like flies?

PMID- 7809943
TI  - Imprinting: the embryo and adult point of view.

PMID- 7809942
TI  - Transposon tagging in heterologous host plants.

PMID- 7809944
TI  - A model for specification of the left-right axis in vertebrates.
AB  - The mechanisms that underlie the formation of the left-right embryonic axis in
      vertebrates are not known. The programmed pattern of cell-type change in fission
      yeast results from the inheritance of specific chromatids of the parental
      chromosome. Here, I address how such a model may explain left-right specification
      of the viscera in mice. The model proposes that DNA replication produces
      different chromatids, and that these specific chromatids of both homologs are
      nonrandomly segregated to daughter cells to specify the left-right axis of the
      embryo. Such a model presents a simple explanation of the interesting phenotype
      of the newly discovered insertional mutation inv in mice, which causes reversal
      of the left-right axis, proposing that it is caused by a chromosomal inversion.

PMID- 7809945
TI  - All muscles are not created equal.
AB  - The muscles of an individual vary in their morphological and contractile
      properties and in their patterns of innervation. At one time, it was thought that
      a fairly homogeneous population of myoblasts gave rise to myotubes that were
      subsequently instructed to diversify by various extramuscular factors. There is
      now, however, considerable evidence that myoblasts are heterogeneous, and that
      heritable differences among them interact with environmental influences to give
      each muscle its distinct characteristics.

PMID- 7809946
TI  - Prokaryotic translation: the interactive pathway leading to initiation.
AB  - Finding answers to the many open questions concerning the mechanism and control
      of prokaryotic translation remains one of the central challenges of molecular
      biology. In fact, recent experimental data even force us to reconsider aspects
      that were previously thought to be established fact. Here, we attempt a synthesis
      of new and not-so-new information, which leads to a revised and testable working
      hypothesis for translational initiation.

PMID- 7809947
TI  - RAP1: a protean regulator in yeast.
AB  - The yeast protein RAP1 is a sequence-specific DNA-binding protein that binds to
      many promoters, to two elements that silence mating-type genes, and to [(C)1-3A]n
      tracts at telomeres. RAP1 is essential for cell viability and can function as
      either an activator or a repressor of transcription, depending upon the context
      of its binding site. Recent experiments suggest that its function may be
      determined by different sets of protein-protein interactions at promoters and
      silencers. At the ends of chromosomes, RAP1 plays an important role in both
      silencing (telomere position effect) and telomere structure.

PMID- 7809948
TI  - Receptors on the agenda: a symposium to honour Sir James Black.

PMID- 7809949
TI  - Association between glucocorticosteroids and lipocortin 1.

PMID- 7809950
TI  - Does the HIV-1 coat protein gp120 produce brain damage?

PMID- 7809951
TI  - Agonist-antagonist interactions at angiotensin receptors: application of a two
      state receptor model.
AB  - Interactions between agonists and antagonists at angiotensin receptors are
      characterized by a number of features: variation of antagonist dynamics between
      apparent simple competition, insurmountable antagonism and, occasionally,
      augmentation; the tendency for insurmountable antagonism to be saturable; slow
      recovery of agonist responses following agonist-induced tachyphylaxis; and the
      ability of competitive antagonists to accelerate recovery from the latter
      intervention. Some of these phenomena have also been observed in studies of 5-HT2
      receptors where they were attributed to the operation of a two-state model with
      an allosteric site. In this article, Mark Robertson and colleagues propose that
      the properties of angiotensin AT1 receptors may be explained by a similar model,
      but without the need to evoke an allosteric site.

PMID- 7809952
TI  - Beta-adrenoceptors, cAMP and airway smooth muscle relaxation: challenges to the
      dogma.
AB  - beta-Adrenoceptor agonists are assumed to induce airway smooth muscle relaxation
      through the cAMP-protein kinase A (PKA) phosphorylation cascade system. This
      traditional second messenger paradigm of beta-adrenoceptor agonist action is
      deeply engrained, but in this article Theodore Torphy reviews recent observations
      that force a re-examination of the dogma. For example, cAMP can activate protein
      kinase G as well as PKA, and this unanticipated dual action may contribute to the
      relaxant activity of cAMP. Other studies suggest that beta-adrenoceptor agonists
      can induce relaxation by a cAMP-independent mechanism involving a direct coupling
      of the beta-adrenoceptor to Ca(2+)-dependent K+ channels. Consequently, it is
      possible that multiple cAMP-dependent pathways act in concert with cAMP
      independent pathways to mediate bronchodilation in response to beta-adrenoceptor
      agonists.

PMID- 7809953
TI  - Dopamine receptor agonists, partial agonists and psychostimulant addiction.
AB  - Despite the epidemic growth of psychostimulant addiction over the past years, few
      pharmacological means of intervention are available to date for clinical
      treatment. This is of importance since the withdrawal syndrome that follows
      abstinence from drugs such as cocaine and the amphetamines is characterized,
      among other symptoms, by intense craving for the abused drug, and this is
      considered a critical factor leading into relapse of drug use. In this article,
      Luigi Pulvirenti and George Koob focus on the modulatory role shown by drugs
      acting at the dopamine receptor on the various phases of psychostimulant
      dependence in preclinical models and in human studies, and suggest that a class
      of compounds with partial agonist properties at the dopamine receptor may have
      therapeutic potential.

PMID- 7809954
TI  - The current endothelin receptor classification: time for reconsideration?
AB  - The possible involvement of endothelins in a variety of diseases has attracted
      the attention of many pharmacologists in search of a novel therapeutic approach.
      The rapid development of endothelin research has resulted in the molecular
      characterization and pharmacological recognition of ETA and ETB receptors, and in
      the development of compounds selective for these receptors. However, the
      characterization of receptors in various assays has shown that a number of
      effects are mediated by receptors that do not fit the present criteria for ETA or
      ETB receptors. In this article, Willem Bax and Pramod Saxena address endothelin
      receptors in general, and atypical receptors in particular.

PMID- 7809955
TI  - The potential for safer anaesthesia using stereoselective anaesthetics.
AB  - The molecular mechanisms by which inhalational agents produce anaesthesia remains
      a subject of controversy, despite a history of clinical use spanning two
      centuries. The demonstration of a significant difference in the anaesthetic
      potencies of (+)- and (-)-isoflurane provides compelling evidence for the
      hypothesis that proteins, rather than lipids, are the primary sites of
      anaesthetic action. Moreover, the optically active isomers of volatile
      anaesthetics provide new tools to discriminate among putative molecular targets
      of anaesthesia. A difference in the anaesthetic potencies of (+)- and (-)
      isoflurane, together with an apparent lack of stereoselectivity in their
      myocardial suppression, raises the possibility that an optically active volatile
      agent may have clinical advantages over currently available racemic mixtures.

PMID- 7809956
TI  - [The effect of sodium and ouabain on the activation of beta 2-adrenoreceptor
      dependent adenylate cyclase in human lymphocytes].
AB  - Sodium inhibitory effect on adenylate cyclase activity of human mononuclear
      lymphocytes was investigated. Adenylate cyclase sensitivity to sodium inhibition
      was different upon cyclase stimulation with 1-isoproterenol, Gpp(NH)p and NaF.
      Sodium half-maximum inhibitory doze (ID50) was the smallest for 1-isoproterenol
      stimulated adenylate cyclase activity (-40 mM). Cholera toxin did not exert
      influence on the inhibition of adenylate cyclase by sodium. Ouabain (10-100
      microM) increased ID50 by 1.5 fold only for 1-isoproterenol-stimulated cyclase.
      It was observed that ID50 decreased after a short-term (15 min) 1-isoproterenol
      activation of intact lymphocytes. It is possible that the smallest sodium ID50
      for 1-isoproterenol-stimulated adenylate cyclase is conditioned by sodium
      interaction with carboxylate residue of aspartate-79 from the cytoplasmic
      compartment of beta 2-adrenergic receptor (Horstman et al., 1990).

PMID- 7809957
TI  - [The resistance of Amoeba proteus amebae with different levels of nuclear DNA to
      the action of high temperature and ethyl alcohol].
AB  - Thermotolerance and resistance to ethyl alcohol were investigated in Amoeba
      proteus of polyploid series. Thermoresistance of these amoebae was determined by
      measuring the mean time of survival at the lethal temperature (43 degrees C). The
      resistance to ethyl alcohol was estimated by the mean percentage of individuals
      that survived following a 5-minute treatment with 7.5% ethyl alcohol. Neither
      thermotolerance, nor ethyl alcohol resistance were found to depend on the amount
      of nuclear DNA. It was also established that colchicine did not induce a
      hereditary instability of thermoresistance in amoebae.

PMID- 7809958
TI  - [The cellular reaction to heat shock: the physiological aspect].
AB  - This review regards the basic manifestations of cell response to heat-shock (HS):
      formation of resistance increase or acquired tolerance, and contribution of
      stress proteins (SP) to this reaction. This to great extent nonspecific increase
      in heat-shock cell resistance is based on two processes: a) an increase in the
      initial heat resistance of cell functions which results from enhancing of
      resistance of native efficient state of cell protein macromolecules to
      denaturating agents; b) stimulation of cell repair capacity that is expressed as
      an increase in the rate of cell function restoration in the case of its equal
      extent of damage in trained and untrained cells, and as expansion of the
      repairable zone (the interval of temperatures within the limits of which the
      function is inhibited completely, but reversibly after certain duration of
      heating). Stimulation of cell repair capacity is due to a more rapid renativation
      or substitution of proteins modified by stress. Both the processes (a and b)
      provide the ability of trained cells to function under higher temperature,
      compared to untrained ones. This review shows that heating, as well as any other
      denaturating agent as an inadequate stimulant, can give rise to synthesis of new
      proteins and other metabolites or to enhance running synthesis of substances. The
      fact of protein synthesis stimulation does not provide grounds to attribute an
      adaptive function to these proteins. SP are unable to increase the initial heat
      resistance of cell functions, but participation of some SP (chaperons) in
      stimulation of cell repair capacity is highly probable. In the same time the
      repair of heat injured cells can take place without protein synthesis. In some
      cases the acquired tolerance remains for several weeks after HS. A comparison of
      cell responses to HS and to medium temperature increase within the tolerant
      limits (temperature adjustment) shows that their adaptive mechanisms are
      evidently different, although the increase in the initial heat resistance of some
      functions and stimulation of cell repair capacity take place under the
      temperature adjustment.

PMID- 7809959
TI  - [An analysis of the chromosomal combinations in dicentrics with induced telomeric
      fusion].
AB  - Chinese hamster heteroploid cell culture was treated by colcemide for 42 h, of
      which within the first 17 h by 5-bromedeoxyuridine. Dicentric chromosomes, that
      were formed at the 2nd mitosis after colcemide administration, were analysed
      using G-banding. Of 211, only 40 were made of heterological dicentrics. Other 171
      dicentrics were formed by telomeric fusion of autological chromosomes. No
      correlation was found between the length, centromeric index and frequency of
      dicentric formation. A probability of telomeric fusion of chromosomes determined
      by nucleotide sequences specific for each chromosome is proposed.

PMID- 7809960
TI  - [Seasonal transformations in the lampbrush chromosomes and the morphogenesis of
      the karyosphere capsule in Rana temporaria oocytes detectable by an analysis of
      the isolated nuclear structures].
AB  - A study was made of the seasonal changes in lampbrush chromosomes, accompanying
      structures and the karyosphere capsule, isolated from diplotene oocytes of Rana
      temporaria of stages 3-6 of oogenesis, as classified by Dumont (1972). The frogs
      were collected from their hibernation sites. The formation of fibrillar material
      of the karyosphere capsule was followed from stage to stage. Isolation of nuclei
      by hand, and dispersal of their content was carried out as described by Callan
      (Callan, 1986; Callan et al., 1987). A modified Miller's method (Miller, Beatty,
      1969) was used for the ultrastructural analysis. The examination of lampbrush
      chromosomes shows that they change from season to season (summer, autumn,
      winter), reaching the maximum size in summer (Fig. 2). In autumn their
      transcriptional activity decreases, although their size remains unchanged. In
      this period each transcription unit of lateral loops contains about IO RNP
      fibrils per 1 mkm, whereas in summer their number is 20 per 1 mkm (Fig. 4, 5). A
      large number (about 100 per each bivalent) of spheroidal granules about 1.8 mkm
      in diameter appear around the autumn bivalent (Fig. 3). They constantly accompany
      the chromosomes and therefore are called satellites. In winter, the satellites
      are of variable diameter (0.8-5.3 mkm) and still bound to lateral loops of
      chromosomes. The loops are notably reduced, and the association of the satellites
      shortened, to aggregate into knots.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7809961
TI  - [Localization of the CD4 receptor gene in the chromosomes of clone cells of the
      monocytoid line U-937 characterized by different sensitivities to HIV].
AB  - Karyotypes of two clones of U-937 line, with high and low sensitivity to HIV-1,
      were studied. The CD4-receptor gene-cellular receptor of HIV-1 was mapped. CD4
      receptor gene was located according to in situ hybridization method, in locus 12
      p11-p12, both in cells of high-sensitive clone U-937/16, and in cells of low
      sensitive clone U-937/4. It is determined that in both the clones chromosomes 12
      are presented in two copies and are not affected by rearrangements. That allows
      to conclude that the sensitivity of cells U-937 to HIV-1 does not depend on the
      dose of this gene, or on its transference in chromosomes.

PMID- 7809962
TI  - [The effect of the activation of lipid peroxidation on the structure of
      extraembryonic organs and the liver in rats at different periods of ontogeny].
AB  - The influence of activation of lipid peroxidation (LP) on morphofunctional
      organization of extraembryonic compounds and liver on different stages of rat's
      ontogenesis was studied. It is found that LP-activation (paraquat injection) in
      late pregnancy leads to extensive vacuolization of trophoblastic and yolk sac
      cells. In the embryonic liver, the number of hemopoietic cells decreases. During
      the first days after LP activation in the liver of adult animals, enlargement of
      granular endoplasmic reticulum elements and their degranulation were revealed. In
      the liver cells of the offsprings, administered paraquat prenatally, signs of
      bile formation activation were detected.

PMID- 7809963
TI  - [Oncogenesis in transgenic mice].
AB  - Oncogenesis in transgenic mice is at present a model, most adequately reflecting
      the natural conditions of tumor development. One of more important traits of this
      model is that it allows to study malignant growth simultaneously at all the
      structure-function levels in the context of the whole organism. This paper is a
      review of results of a series of experiments in which the localization of tumors
      was dependent or independent on the tissue specificity of a promoter, as well as
      development of multiple tumors with the use of viral regulatory sequences in
      genetic constructions. It has been shown that although a transgene is expressed
      in most of the tissues, tumors develop in some particular tissues only. These
      observations are interpreted by some authors in favour of the concept of
      multistep cancerogenesis. In this view, of primary importance are the results of
      studies on oncogenesis in transgenic mice, which contradict this concept and are
      regarded by their authors as an evidence of the possibility of a one-step
      transformation of normal cell into malignant one. The analysis of the obtained
      material enabled us to put forward an assumption that the key role in oncogenesis
      is played not only by certain genetic disturbances, but also by multi-level
      homeostatic mechanisms. Apparently, it is just the transgenic mice with cellular
      or viral oncogenes in their genome that represent a more adequate model for the
      detection of certain molecular-biological mechanisms underlying these
      disturbances. Also, of much importance is abundant material accumulated by now on
      oncogenesis of transgenic mice which shows a possibility of the effective use of
      various genetic constructions with prokaryotic and eukaryotic regulatory
      sequences, a possibility to induce not only tumors of some particular tissues,
      but also multiple hyperplastic and neoplastic changes in one and the same mouse.
      Development of tumors in such transgenic mice can be regarded as a model of
      different types of cancer disease.

PMID- 7809964
TI  - [An electron microscopic study of the quantitative characteristics of the
      neuronal and synaptic architectonics of the central and lateral nuclei of the
      amygdaloid body in the rat brain].
AB  - Some fine structural features of neurons and synapses in the central and lateral
      nuclei of rat's amygdala have been described. Neurons of the central nucleus are
      comparatively alike, but neurons of the lateral nucleus are distinguished by
      size, form and distribution of cell organelles. Different varieties of axonal
      profiles in both the nuclei are described. The axonal profiles are distinguished
      by quantity, form and localization of vesicles, presence or absence of an active
      zone, localization of profiles on different parts of neurons--soma, spines, fine
      dendrites and shafts. The axo-dendritic synapses were investigated
      quantitatively.

PMID- 7809965
TI  - [Changes in the cell membrane permeability of chick myoblasts in primary culture
      when in contact with rat neutrophils].
AB  - The reaction of chicken myoblasts in competent primary culture during their
      contact with activated rat neutrophils was evaluated. In the incubation medium
      dynamics of activities were defined for proteinases and creatine kinase, protein
      content, as well as for DNA and protein marked precursor increase. An increase in
      myoblast membrane permeability has been revealed. It is shown that the culture is
      a sensitive model for investigation of physiological interaction of neutrophils
      with muscle tissue cells.

PMID- 7809966
TI  - [The epidermal growth factor induces specific changes in the expression of small
      RNA and of the set of small RNP in A-431 cells].
AB  - Specific small ribonucleoprotein (alpha-RNP) complexes have been identified and
      characterized in the human epidermal carcinoma A-431 cells. The alpha-RNP
      complexes contain Alu-homologous small RNA, along with other small antisense RNA
      species. The epidermal growth factor (EGF) has been shown to induce selective
      specific changes in the expression of the small alpha-RNAs, the expression of the
      Alu-like RNA being repressed. Specific changes in the protein composition of the
      alpha-RNP complexes have been detected under the influence of EGF.

PMID- 7809967
TI  - [The isolation and phenotypic characteristics of heat-resistant cells from the
      Chinese hamster CHO-K1 line].
AB  - By sequential selection for a resistance to a short-term heating at 45 degrees C,
      two independent clones, CHSR5 and CHSR6, have been isolated from ovarian cells of
      the Chinese hamster (CHO-K1). A subline CHO-A40, capable of proliferation at 40
      degrees C, has been obtained as mass culture by culturing CHO-K1 cells for 2
      months at 40 degrees C. The lines obtained have no cross-resistance to the
      temperature used in their selection: the CHSR5 and CHSR6 cells are not capable of
      reproduction at 40 degrees C, while the CHO cells do not survive over a 60 min
      heating at 45 degrees C. This bears evidence that mechanisms, underlying the cell
      resistance under different thermal regimens used, may be different. The heat
      resistant sublines maintain their heat resistance for 6 months of cultivation at
      37 degrees C. The acquisition of heat resistance by cells correlates with their
      high primary resistance, and with their resistance to colchicine and actinomycin
      D.

PMID- 7809968
TI  - [The repair of UV-induced postreplication DNA gaps in Escherichia coli cells
      adapted to methylmethane sulfonate and ethylmethane sulfonate].
AB  - The survival (only after the adaptation to methylmethane sulfonate, MMS) and
      repair of DNA postreplication gaps in UV-irradiated Escherichia coli, adapted to
      MMS (20 mkg/ml for 3 h) and ethylmethane sulfonate (EMS, 100 mkg/ml for 3 h),
      have been investigated. The survival of MMS-adapted bacteria of wild strains B/r
      and K12 AB1157 somewhat increased, whereas the survival of AB1886 uvrA mutant,
      which unlike the wild type bacteria is unable to excise cyclobutane pyrimidine
      dimers, was seen to decrease. The repair of postreplicative gaps in MMS-adapted
      bacteria correlates qualitatively with changes in survival: in B/r and AB1157
      strains the repair is somewhat more effective (10-15%), while in AB1886 uvrA
      mutant significantly slower (near 30%) than in non-adapted bacteria. Similar
      changes of postreplicative repair (PRR) of DNA are observed in AB1157 and AB1886
      uvrA strains adapted to EMS. It is suggested that the decreased efficiency of PRR
      in bacteria AB1886 uvrA, adapted to alkylating agent, may be due to the
      interference between the two inducible repair processes: adaptive response and
      SOS response. The latter process is involved in the repair of some part of
      postreplicative gaps of DNA. Different results of PRR of DNA in bacteria of wild
      types, adapted to MMS and EMS, may be associated with the intrinsic PRR in uvr+
      strains. Due to this process in uvr+ bacteria SOS component of PRR of DNA is not
      formed. It is suggested that PRR in uvr+ bacteria adapted to alkylating agents is
      accelerated by enzymes of adaptive response in the absence of antagonism between
      the SOS response and the adaptive response.

PMID- 7809969
TI  - [A cytofluorimetric study of the glycogen content and of the enzymatic activity
      of its metabolism in human and animal hepatocytes in liver cirrhosis and during
      rehabilitation].
AB  - Reversibility of hepatocyte functional activity is shown by cytofluorometric and
      microbiochemical methods in human and rat liver during postcirrhosis
      rehabilitation. Contents of the total glycogen and its fractions in liver cells
      were defined on smears of isolated hepatocytes obtained from the live puncture
      liver biopsies. A double increase of glycogen level is shown, in average, in
      hepatocytes during experimental liver cirrhosis in rats. At the same time, a
      relative content of the hard soluble fraction of glycogen increases by 5-8 times.
      The glycogen level falls to reach the norm already within one month after
      shutting off the pathogenic influence. However, in some animals after 6 months
      this level becomes even lower than the normal one. Again, the ratio between the
      hard soluble fraction and light one remains. In men with cirrhosis glycogenosis
      of hepatocytes can be expressed in greater degree (increase by 4-5 times): it
      depends on the illness heaviness. Further changes in glycogen content depend on
      the pathological process development. Under experimental cirrhosis the activity
      of glucose-6-phosphatase decreases by 4.3 times. Within one month after stopping
      the pathogenic influence the activity of this enzyme increases by 3-4 times, but
      later, in 6 months, it decreases to reach 55-65% of the norm. No actual changes
      were observed in the activities of other enzymes.

PMID- 7809970
TI  - [Pathological mitoses in clones of the RA-2 subline of rat transplantable
      rhabdomyosarcoma selected for increased and decreased frequencies of the
      formation of spontaneous micronuclei].
AB  - Cell substrains with increased and decreased spontaneous levels of micronuclei
      have been obtained by artificial selection. Clones of the substrains were
      investigated for mitotic division fidelity. About 200 mitoses were investigated
      in each clone. Frequencies of mitotic abnormalities such as ana- and telophases
      with bridge, chromosome and fragment delays at ana- and telophases, scattered
      chromosomes, chromosomes dislocated from spindle at metaphases and tripolar ana-
      and telophases were significantly higher in substrains with increased level of
      micronuclei. This finding indicates that reasons for arising of spontaneous
      micronuclei and alterations in mitotic division fidelity are the same or closely
      related. These reasons can be amplified as a result of the artificial selection.

PMID- 7809971
TI  - [Ribosomal RNA synthesis and the count and type of nucleoli in rat hepatocytes].
AB  - Changes in the activity and number of nucleoli has been studied in hepatocytes of
      the same rat before and after partial hepatectomy. In the latter case, the rate
      of ribosomal RNA (rRNA) synthesis was increased by a factor of 1.7, on the
      average. The synthesis was evaluated by incorporation of adenosine triphosphate
      in situ after alpha-amanitine treatment of squashed cells. In 2c, 4c and 8c
      nuclei, the number of labeled nucleoli was less than in nucleolonemic nucleoli
      stained with silver nitrate. These values were drawn together during stimulation
      of rRNA synthesis but the difference was often preserved especially for highly
      ploid nuclei. The lack of activity in part of nucleolonemic nucleoli was assumed.
      After stimulation of RNA synthesis, the number of nucleolonemic and satellite
      nucleoli decreased, while the size of preserved nucleoli was enlarged. The number
      of nucleoli did not correspond to the nuclear ploidy; their total size was
      proportional to the gene dosage. The mean level of rRNA synthesis was similar in
      nuclei of the same ploidy with two, three and four nucleoli. A great variability
      was detected in the rate of rRNA synthesis as well as in the number of
      nucleoloneme and satellite nucleoli in hepatocytes of the control and
      experimental rats. Some difference was observed in the label degree for nucleoli
      of the same nucleus.

PMID- 7809972
TI  - [The interrelation between the morphological characteristics of the nucleolar
      apparatus in cultured human embryonic fibroblasts and the proliferative activity
      of the cells].
AB  - A relationship between the number of AgNOR, nucleolar area, the number of
      nucleoli per nuclei, the number of nucleoli touching nucleolar membrane and the
      proliferating activity of human embryonal fibroblast culture was investigated.
      Cell proliferation was arrested by serum deprivation. In 10 days, initiation of
      proliferation was performed by cessation of serum deprivation. The strongest
      correlation (r = 0.96) was found between the index of labeling (IL) and the
      number of nucleoli touching nucleolar membrane. A strong correlation was also
      observed between AgNOR count, nucleolar area and IL. The number of silver grains
      in the interphase nucleus decreased slowly and increased quickly, with quick
      decrease and increase of cell proliferation occurring, respectively. No
      correlation was found between the number of nucleoli and IL.

PMID- 7809973
TI  - [Calcium and magnesium ion-dependent endonuclease 37 kDa is activated during
      colchicine-induced apoptosis in HL-60 cells].
AB  - With the aim of revealing endonuclease(s), activating in apoptotic cells, a
      nuclease activity of nuclear protein extract from human leukemic HL-60 cells
      treated with colchicine was studied. After a 30 h incubation with colchicine, a
      specific DNA fragmentation--a multiple of 200 base pair subunits--was clearly
      observed that was an evidence for the endonuclease activation. After 48 h almost
      the whole DNA was fragmented. At the same time histones appeared the major
      proteins of nuclear extract. Using the method for detection of nuclease activity
      in a gel, protein 37 kDa was identified as a Ca2+, Mg(2+)-dependent endonuclease.
      The maximum increase in nuclease activity occurred after a 24 h incubation with
      colchicine. A low activity of this protein was also found in control cells. These
      data suggest that in apoptotic cells activation of constantly expressed nucleases
      may occur, rather than a new synthesis of apoptotic nucleases.

PMID- 7809974
TI  - [The role of the endoplasmic reticulum in the formation of specialized cellular
      organelles in parasitic Sarcosporidia].
AB  - A cytological study was made of participation of the endoplasmic reticulum in the
      formation of specific cell organelles in Sarcocystis muris zoites. The data
      presented in this paper confirm our earlier assumption (Radchenko, 1987) that the
      Golgi adjunct is a structure made of four membranes of the smooth endoplasmic
      reticulum (ER) channels. This organelle appeared to be available in all the three
      cell types recognized within the sarcocyst: metrocytes, intermediate cells and
      merozoites. In the dividing metrocytes and intermediate cells the Golgi adjunct
      is turning progressively in a polar ring, whose membranes are covered with a
      fibrillar material from which subpellicular microtubules are formed. It has been
      first shown that ER channels are involved in the formation of amylopectin
      granules and immediate glycoprotein regions around them. Large spiral structures,
      composed of the ER channels, were seen in the zoite cytoplasm. Besides,
      micronemes were also made of closely packed ER channels. It looks likely that
      individual micronemes may be connected to each other through these channels.

PMID- 7809975
TI  - [An immunocytochemical analysis of the hormonal status of animals transgenic for
      growth hormone genes and for a mini-gene of human growth hormone-releasing
      factor].
AB  - An immunocytochemical analysis of hormonal status of transgenic rats containing
      human growth hormone gene has been done. The enhanced expression of the
      endogenous growth hormone gene was demonstrated with poly- and monoclonal
      antibodies inside somatatropes of pituitary. No activity of the heterologous
      growth hormone gene was revealed in kidney, pancreas or liver as it might be
      expected according to specificity of MT1 and TAT promotors. Transgenic animals of
      F0, F1 and F2 generation exhibited disturbance of functional morphology of
      glucagon and insulin producing cells. Lymphocyte infiltration was found in
      pancreatic islets. The transgenic rabbits and swine with the gene of releasing
      factor of human growth hormone did not reveal any severe disturbance. Although
      one swine demonstrated alterations in glucagon producing cells and one rabbit
      revealed a disturbed morphology of the stomach tissues. The data are discussed in
      relation to general problems of transgene activity and interaction with
      endogenous homolog.

PMID- 7809976
TI  - [Damage to and interphase death of Ehrlich ascites carcinoma tumor cells at
      different growth stages during energy starvation and heat shock].
AB  - The reaction of the Ehrlich ascite carcinoma cells, being at different phases of
      their growth, to the energy deprivation (rotenone in glucose-free medium) and
      heat shock (HS) was investigated. The criteria of this reaction were interphase
      death (according to Trypan blue staining) and structural changes (appearance of
      big blebs). It was found that proliferating cells (from log phase), judging from
      the two criteria, were more sensitive to a separate action of both energy
      deprivation and HS, than the resting ones (from stationary phase). Under combined
      actions (energy deprivation plus HS), when cell damage is much accelerated, the
      difference in their sensitivity was revealed only in relation to structural
      damages. Under the action of starvation and HS, changes in ATP content in the
      cells of both ages were similar; the reaction of cells to both the agents, after
      removing the calcium from medium (by chelator), was not changed. It means that
      specificity of the reaction of cells being at different growth phases to the
      damaging agents is not determined by disturbance in their energetic and calcium
      homeostases. In the proliferating cells, the cytoskeletal protein aggregation
      under energetic deprivation proceeded faster than that in the resting ones. It is
      proposed that the reaction of cells being on different growth phases depends on
      the stability of cytoskeletal proteins and on the content of stress proteins.

PMID- 7809977
TI  - [The effect of mycoplasmal contamination of cultures of skin fibroblasts from the
      Indian muntjac and of the subsequent decontamination of the cultures using
      ciprofloxacin on the karyotypic structure of the cell line].
AB  - The karyotypic variability of Indian muntjac skin fibroblast cell line, cultured
      for 95-168 days after contamination with Acholeplasma laidlawii strain PG-8, has
      been investigated. The contaminated cultures differ from noncontaminated ones in
      cell distribution for chromosome number. The noncontaminated cultures have modal
      number of chromosomes equal to 7 with the main structure variant of the karyotype
      (SVK) 2+2+1+1+1. In the contaminated cultures the cell number with 7 chromosomes
      and the main SVK 2+2+1+1+1 decreased, whereas the cell number with 6 chromosomes
      increased along with the main SVK 2+2+1+1 resulting from the loss of chromosome
      Y1. The treatment of cells with ciprofloxacin for mycoplasma decontamination did
      not restore the normal cell distribution for chromosome number. The frequency of
      chromosomal aberrations, mainly dicentrics, due to telomeric associations,
      increased after 95-168 days of cultivation of contaminated cells. Chromosomes 1
      and 2 and their combination are mainly involved in dicentric formations. The
      treatment of contaminated cells with ciprofloxacin restores the initial frequency
      of chromosomal aberrations. Chromosomes with altered structures have not been
      demonstrated. It has been shown that cells became mycoplasma-free after 15 days
      of treatment with ciprofloxacin. The role of aneuploidy and dicentrics in cell
      adaptation to culture conditions is discussed.

PMID- 7809979
TI  - [A comparison of the amount of DNA in the nuclei of the sporoplasm of 2 species
      of parasitic protozoans of the Myxozoa type--Myxosoma cerebralis and
      Triactinomyxon gyrosalmo].

PMID- 7809978
TI  - [Na+ and K+ ion transport across the human erythrocyte membrane during the
      formation of nystatin channels under in-vitro conditions: the characteristics and
      an analysis of the processes].
AB  - The kinetic properties (the spontaneous lysis velocity, the time of achievement,
      and the concentration level of the stationary stage) are shown to be strongly
      different, while the human erythrocytes are resuspended in various salt media.
      The analysis of Na+ and K+ concentrations, under the effect of a polyene
      antibiotic nistatin, on the human erythrocytes as an integral kinetic function of
      time is carried out. The processes engaged in this kinetic function are
      characterized.

PMID- 7809980
TI  - [The effect of sodium butyrate and luminol on reciprocal exchanges and gene
      conversion during extrachromosomal DNA recombination in cultured animal cells].
AB  - For determination of the extrachromosomal homologous DNA recombination
      efficiency, somatic cells of various lines have been transformed with plasmid
      DNAs which contain copies of neo-gene with non-overlapping deletions.
      Reconstruction of the neo-gene functional activity, which imparts a geneticin
      resistant phenotype to cells, indicates that recombination has occurred. If dP1
      and dR copies of the neo-gene are used, a single (reciprocal) exchange is
      necessary for reconstruction of the neo-gene by homologous DNA recombination, but
      a double exchange (gene conversion) is needed in the case of dP1 and dS copies.
      It is shown that in human cells of line HeLa and in mouse cells of line LMtk-, in
      contrast to the Chinese hamster cells of line A238, the frequency of double
      exchanges is comparable to that of the single DNA exchanges which is an evidence
      of participation in DNA recombination of gene conversion in addition to a single
      exchange mechanism. The treatment of cells with sodium butyrate and luminol
      exerts different influences on the rate of the single DNA exchanges and on that
      of gene conversion (double exchanges) in cells of lines LMtk- and HeLa,
      respectively. Essential distinctions in correlation of the single DNA exchange
      frequency and the gene conversion frequency in cells of the studied lines, and
      the possibility to distinguish between these mechanisms of recombination, under
      the treatment by sodium butyrate and luminol, may suggest the existence of two
      mechanisms of homologous DNA recombination in cultured animal cells, which
      function independently of one another, to a considerable extent.

PMID- 7809981
TI  - [The antibodies obtained by immunization with a peptide identical to a section of
      the zinc-binding domain of the early growth response 1 factor (EGR-1) interact
      with a 102-kDa protein from mouse fibroblasts].
AB  - The early growth response (EGR) genes represent a family of proteins whose
      structure includes zinc finger domain(s) interacting with a specific site in
      promotors of different genes to regulate their transcriptional activity. Using as
      an antigen a short sequence RSDHLTTHIR from the middle zinc finger sequence of
      EGR-1 we have generated a clone of hybridoma cells producing a monoclonal
      antibody (mAb) that binds a 102 kDa protein, but does not bind EGR-1 protein. The
      102 kDa protein consists apparently of 2 polypeptides, of 58 kDa and 44 kDa, and
      its expression is strongly stimulated in serum-induced mouse fibroblasts.

PMID- 7809982
TI  - [The mechanisms of the joint effect of chorionic gonadotropin and recombinant
      interleukin-2 on the splenocytes during the formation of a humoral immune
      response].
AB  - In the spleen cell culture of female mice (CBA x C57BL/6)F1, transduction
      mechanisms of associative effect of chorionic gonadotropin (CG) and recombinant
      interleukin 2 (IL-2) have been investigated. The functional activity of
      splenocytes was estimated in the syngeneic transfer system, according to the
      number of plaque forming cells. It has been established that a 1 hour incubation
      of CG (40-200 IU) with intact spleen cells in vitro suppresses their ability to
      form the adoptive immune response. On the contrary, the common hormone effect
      with IL-2 (150 IU) increases more than twofold the plaque forming cell number.
      The costimulating effect of hormone is dose-dependent and is revealed only upon
      utilization of a high CG concentration, while in a low concentration and on the
      background of IL-2, the hormone completely loses its independent immunodepressive
      effect. During addition of cells, inhibiting the secondary messengers formation,
      to the culture it has been determined that the CG-dependent costimulation is
      completely lost during the blockade of "slow" Ca(2+)-canals, and partly lowered
      during the inhibition of phosphatidylinositide resynthesis processes. The
      hormonal and interleukin signal transduction in their common effect does not
      depend on prostaglandin synthesis. The independent immunostimulating IL-2 effect
      is displayed only on the background of blockade of cyclooxygenase enzymes or
      inositol-1-monophosphatase.

PMID- 7809983
TI  - [The long-term limitation of the proliferation of cells in culture does not lead
      to their proliferative aging].
AB  - A hypothesis was tested about a long-term limitation of cell proliferation as the
      primary cause of their senescence and, consequently, the senescence of the whole
      organism. Both half-yearly and yearly maintenance of mouse fibroblast-like cells
      L-929 in a high density permanent culture with low level of mitotic activity
      (less than 1 mitosis per 10,000 cells) has not revealed any irreversible changes
      in their proliferative features and has not confirmed the hypothesis under
      examination.

PMID- 7809984
TI  - Effects of poor forage conditions on the behaviour of grazing ruminants.
AB  - This paper shows that the study of animal behaviour is a valuable aid to the
      improvement of the management of grazing livestock under extensive conditions.
      The food available to grazing animals in developing countries, and particularly
      in the dry season in the tropics, is often of very low quality and, in addition,
      is frequently available at low densities per unit area. Grazing ruminants attempt
      to adapt to these adverse conditions by increasing the time for which they graze
      each day and also by dispersing more widely. However, the time for which animals
      can graze may be limited by solar radiation and fly irritation in the day, and by
      the confining of the animals in pens at night. The adverse effects of the above
      limitations may be partially overcome when adapted local breeds are used.
      Dispersion of animals improves their ability to make use of extensive pasture and
      in order to encourage it, an understanding of the factors that affect it such as
      breed differences, social behaviour, adaptation and location of watering points
      and other unique environmental factors must be achieved. The paper concludes with
      recommendations of areas worth further research.

PMID- 7809985
TI  - Comparative study of trypanosomosis in zebu and N'Dama cattle in The Gambia.
AB  - An experiment was conducted in The Gambia to compare trypanosomosis incidence
      between zebu and N'Dama cattle. It was considered important to compare the 2
      breeds under identical management conditions and the animals were maintained
      together at 3 locations, traditionally managed and under a range of tsetse
      challenges. The results show that trypanosomosis incidence was significantly
      higher in zebu than in N'Dama. Titre of antibody against Trypanosoma vivax
      measured by an IFAT showed a significant difference between zebu and N'Dama.
      Variations in packed cell volume were greater in zebu than in N'Dama.

PMID- 7809986
TI  - Trypanosoma vivax in Colombia: epidemiology and production losses.
AB  - The present paper reports information obtained between 1982 and 1989 in the
      tropical lowlands of the Atlantic coast of Colombia. The studies confirmed that
      Trypanosoma vivax was widely but unevenly distributed within the study area and
      that incidence ranged from sporadic transmission to localised epidemics in which
      virtually all susceptible animals become infected within a period of 3 months.
      Quantitative epidemiological methods substantiated impressions of previous
      workers that T. vivax infections were associated with low-lying swampy areas and
      tabanid activity. Overt clinical trypanosomosis was rare in herds in which T.
      vivax was endemic. However, in these herds primary T. vivax infections were shown
      to cause subclinical alterations in calves. The infection consistently caused a
      temporary depression of packed cell volume (PCV) as well as a reduction in growth
      rate. There was no evidence of compensatory growth at a later stage.

PMID- 7809987
TI  - Rabies virus typing--preliminary survey in Botswana.
AB  - A survey was made of the subtypes of rabies isolates made in Botswana using
      monoclonal antibodies. Two subtypes were detected, termed canine and mongoose.
      The canine subtype predominated in the north and west and appeared to be related
      to the distribution of both the domestic dog and wild jackal. The mongoose
      subtype was found in the south-east and was associated with feline and viverrid
      wildlife. The geographical distribution also matched reports of isolates examined
      in the neighbouring countries.

PMID- 7809988
TI  - Monitoring of highly virulent infectious bursal disease in Botswana 1989 to 1993.

PMID- 7809989
TI  - Foot-and-mouth disease in Ethiopia from 1988 to 1991.
AB  - During the period 1988 to 1991 samples from 16 foot-and-mouth disease outbreaks
      in Ethiopia were examined at the National Veterinary Institute, Ethiopia, and at
      the FAO World Reference Laboratory for Foot-and-Mouth Disease, UK. Typing of the
      virus responsible was possible in 13 of these outbreaks representing 10 separate
      disease events; 8 of these were caused by serotype O and 2 by serotype SAT2. This
      is the first record of the presence of serotype SAT2 foot-and-mouth disease virus
      in Ethiopia. In contrast to earlier studies serotypes A and C were not detected.

PMID- 7809990
TI  - National cross-sectional study of mastitis in dairy cattle in Jordan.
AB  - Between July 1991 and August 1992, 63 Jordanian dairy farms selected by
      stratified random sample were visited to identify the major causes and prevalence
      of intramammary infections in dairy cows. Of 773 cows examined 60% of all sampled
      quarters had > 283,000 cells/ml. The mean value of somatic cell count (SCC) was
      positively associated with age in lactations and negatively with herd size. Cows
      milked by bucket milking machines or in fully automatic parlours had a lower mean
      SCC than those milked by hand. Many management faults pertaining to milking
      procedure and maintenance of milking machines were noted. The most common isolate
      from clinical cases was Staphylococcus aureus (37.5%). Estimates of prevalence of
      bacterial pathogens in intramammary infections were: coagulase negative
      staphylococci (16.04%), S. aureus (9.41%), Klebsiella spp. (6.17%),
      Corynebacterium bovis (5.35%) and Brucella melitensis (4.52%). The results
      demonstrate the essential need for the development of a national mastitis control
      programme.

PMID- 7809991
TI  - Levamisole hydrochloride: an effective treatment for stephanofilarial dermatitis
      (humpsore) in cattle.

PMID- 7809992
TI  - Ivermectin treatment in an outbreak of cerebrospinal microfilariosis in goats in
      Saudi Arabia.

PMID- 7809993
TI  - Climatic adaptation of laying hens.
AB  - Three hundred Warren Isabrown female day old chicks were raised for 18 weeks in 3
      distinct artificial climates described as temperate (20 degrees C, 60% RH), hot
      dry (32 degrees C, 40% RH) and hot humid (32 degrees C, 90% RH). At 18 weeks each
      group was divided into 3 and re-allocated to 3 similar air-conditioned laying
      rooms as during the growing period. Different diets were fed to the 3 groups up
      to 18 weeks. The energy needed in order to produce the same average live body
      weight at 18 weeks was similar in all the 3 climatic chambers. The effect of
      treatments in the growing period was not significantly different (P > 0.05) for
      most of the parameters subsequently measured during the laying period. The
      exception was the body weight gain between 18 and 38 weeks and the food and
      energy intakes. However, apart from the sexual maturity, all these parameters
      were negatively influenced (P < 0.05) by the effect of hot climates during the
      laying period irrespective of method of rearing. The results of this study seem
      to indicate that ambient temperature experienced during the first 18 weeks after
      hatching has little effect on subsequent productivity and that rearing birds at
      high ambient temperature does not acclimatise them to these conditions better
      than rearing them under temperate conditions.

PMID- 7809994
TI  - Accuracy of pregnancy/non pregnancy diagnosis in zebu and crossbred cattle and
      Murrah buffaloes by milk progesterone determination post insemination.
AB  - Milk samples collected on days 0, 6, 20, 22 and 24 post insemination from Sahiwal
      and Tharparkar (zebu) cows, Karan Swiss (Sahiwal x Brown Swiss) and Karan Fries
      (Tharparkar x Holstein Friesian) crossbred cows and Murrah buffaloes were
      analysed for progesterone by enzyme-linked immunosorbent assay to determine the
      accuracy of pregnancy and non pregnancy diagnosis in each of the 3 groups of
      animals. The accuracy of pregnancy diagnosis was markedly improved in cows when
      the milk progesterone values on days 20, 22 and 24 were considered together, and
      a further improvement when the levels on days 0, 6, 20, 22 and 24 were considered
      together particularly in crossbred cows. In contrast, buffaloes exhibited the
      highest degree of accuracy from samples collected on day 24, and improvement in
      accuracy was minimal when values were considered for all 5 days, viz. 0, 6, 20,
      22 and 24 post insemination. Overall, the accuracy of positive pregnancy
      diagnosis was greatest in zebu cows (90.9%) followed by crossbred cows (86.6%)
      and Murrah buffaloes (76.5%) when milk progesterone values on all 5 days were
      considered. The accuracy for negative pregnancy diagnosis was 100% on all days.
      The results suggest that there is a greater variability in oestrous cycle length
      in cattle than in buffaloes, and embryonic mortality is greater in buffaloes than
      in cattle.

PMID- 7809996
TI  - Ochronotic arthropathy: structural and ultrastructural features.
AB  - Fragments of articular cartilage and synovial membrane in a case of ochronosis
      were studied by light microscopy (LM), polarized light, and transmission electron
      microscopy (TEM). Granular and/or shard-shaped pigments were observed in the
      synovia, cartilage, and subchondral tissue, and dispersed pigment was also seen
      in the synovial fluid. Zones of the articular cartilage surface showed small
      erosions near shards, and sometimes, when the degenerative process was in an
      advanced stage, a substitutive fibrosis of the cartilage edge was demonstrated.
      LM and TEM observations of the samples studied revealed an alteration of collagen
      fibrils that appeared wavy and sometimes fragmented with loss of periodicity.
      They were always mixed with the dispersed pigment. A peculiar finding that
      characterized this ochronotic case was the complete absence of inflammatory
      infiltrates or signs of monocyte-macrophage activation. These structural and
      ultrastructural observations suggest that the pigment deposition in the articular
      surfaces was due to the synovial fluid circulation and partially to subchondral
      blood flow, which transports and stores the ochronotic pigments in the synovia
      and cartilage. These etiopathologic elements associated with the mechanical
      pathogenesis naturally present in the joints can contribute to the explanation of
      the pathogenesis and origin of ochronotic arthropathy.

PMID- 7809995
TI  - Electrolyte levels in neoplastic and nonneoplastic human urothelium after ouabain
      treatment: X-ray microanalysis of bulk hydrated samples.
AB  - Samples of neoplastic and nonneoplastic human urothelium were immediately frozen,
      incubated in Krebs' saline and then frozen, or incubated in 10(-5) mol/L ouabain
      in Krebs' saline and then frozen. The frozen specimens were then planed in a
      cryoultramicrotome and examined by low-temperature scanning electron microscopy.
      X-Ray microanalysis was performed on the superficial urothelial cells. Neoplastic
      cells immediately frozen and those incubated in Krebs' saline had significantly
      higher K+/Na+, K+/P, and K+/Cl- ratios and lower Na+/P and Cl-/P ratios than
      nonneoplastic cells. Incubation in ouabain led to a fall in the K+/Na+, K+/P, and
      K+/Cl- ratios and a rise in the Na+/P and Na+/Cl- ratios in both neoplastic and
      non-neoplastic cells and effectively nullified the difference between them. These
      results are consistent with the concept that in neoplasia a primary event is
      stimulation of Na+/H+ exchange, which leads to secondary stimulation of the
      ouabain-sensitive Na+/K+ ATPase pump.

PMID- 7809998
TI  - Renal parenchymal malakoplakia: ultrastructural findings in different stages of
      morphogenesis.
AB  - Light microscopic and ultrastructural findings in five cases of renal parenchymal
      malakoplakia detected in renal biopsy specimens (four cases) or observed at
      autopsy (one case) are reported. The spectrum of ultrastructural changes ranging
      from lamellar and microvesicular phagolysosomal inclusions arranged in a biphasic
      pattern to fully developed Michaelis-Gutmann bodies is described. In three of the
      biopsy cases the lesions appeared to represent early stages of malakoplakia
      lacking classic Michaelis-Gutmann bodies. Especially in this phase of disease,
      ultrastructural investigation can distinguish between this condition and other
      histiocytic interstitial renal processes. The findings show that focal
      cytoplasmic degeneration and autophagolysosomal processes observed in macrophages
      could precede the disturbance in the process of bacterial breakdown that is
      responsible for the peculiar granuloma-like inflammatory histiocytic reaction.

PMID- 7809997
TI  - Submicroscopic profile of Isospora belli enteritis in a patient with acquired
      immune deficiency syndrome.
AB  - Small bowel mucosal fragments from a human immunodeficiency virus-positive female
      patient with chronic diarrhea were investigated by transmission electron
      microscopy, and Isospora belli enteritis was documented. The submicroscopic
      profile was characterized by a moderate abnormality of mucosal architecture with
      reduction in height of villi and hypertrophy of crypts. Stages of both asexual
      (trophozoite, schizont and merozoite) and sexual (macrogametocyte) phases of the
      life cycle of the parasite were identified in the epithelium, always enclosed
      within a parasitophorous vacuole. Moreover, the presence of occasional
      extracellular merozoites in the intestinal lumen and in the lamina propria near
      or within lymphatic vessels was documented. These findings expand the current
      knowledge of this parasite regarding its capacity to survive in an extracellular
      environment and document a possible mechanism by which extraintestinal infection
      can take place.

PMID- 7809999
TI  - Maxillary adenoid cystic carcinoma with annulate lamellae.
AB  - Of 29 reviewed ultrastructural studies of adenoid cystic carcinoma, only 1
      mentions the presence of annulate lamellae. The present report describes a 65
      year-old woman who presented with an adenoid cystic carcinoma in her left
      maxillary sinus. At the light microscopic level, most of the connective tissue
      was loose and myxomatous and contained fine strands, cords, and islands of
      epithelium that in places had a cribriform pattern. The ultrastructural
      appearance was similar to that described by others. Two epithelial cell types
      predominated. The cytoplasm of one type contained mainly ribosomes, and that of
      the other type also had peripheral microfilaments. Also present were pseudocysts,
      lumina with microvilli, and replicated basal lamina. In addition, a number of
      both types of cells contained parallel arrays of cisternae that had regular small
      pores. These were annulate lamellae.

PMID- 7810000
TI  - Urachal cystadenoma with abundant glycogen: ultrastructural study.
AB  - A cystadenoma arose in the urachus of a 32-year-old man. The mass was a
      multilocular cystic tumor filled with light yellow mucoid material. It was
      located in the anterior abdominal wall between the umbilicus and the dome of the
      urinary bladder. Overall, the mass was 14 cm x 8 cm x 5 cm, with the largest
      internal cyst being 6 cm in diameter. The lesion was characterized histologically
      by columnar cells with focal cellular and nuclear stratification. Ultrastructural
      examination revealed columnar cells with abundant glycogen, moderately
      pleomorphic microvilli without prominent filamentous cores, and apical mucin
      vacuoles. Nuclei had pleomorphic contours. An intact basal lamina was present. A
      similar urachal cystadenoma has not been described.

PMID- 7810001
TI  - Ultrastructural and immunocytochemical features of a case of neuroendocrine
      carcinoma developing in a prior ileostomy site.
AB  - A patient who developed a mixed neuroendocrine carcinoma and adenocarcinoma at
      the site of a previous long-standing ileostomy is reported. The neuroendocrine
      features are documented by both ultrastructural and immunocytochemical findings.
      Carcinoma arising in an ileostomy site is rare but has been recorded in patients
      with long-standing ileostomies after colectomy for chronic inflammatory bowel
      disease, as in this patient. Neuroendocrine carcinoma developing in this setting
      apparently has not been described before, however.

PMID- 7810002
TI  - Ultrastructural pathology of human T-cell lymphotropic virus type I
      encephalomyelopathy in a white patient with adult T-cell leukemia/lymphoma.
AB  - A white patient with human T-cell lymphotropic virus type I (HTLV-I)-associated
      adult T-cell leukemia/lymphoma for 10 years died 4 months after the onset of
      spastic myelopathy. Ultrastructurally, the neuropathologic findings consisted of
      dystrophic neurites (spheroids) filled with neurofilaments or electron-dense
      bodies, intense astrocytic reaction with abundant formation of corpora amylacea,
      and multilamellar bodies. Demyelination and spongiform change were absent.
      Viruslike particles resembling HTLV-I were detected adjacent to brain endothelial
      cells.

PMID- 7810003
TI  - Light and electron microscopic study of an invasive cribriform carcinoma with
      extensive microcalcification developing in a breast with silicone augmentation.
AB  - Although recent epidemiologic studies suggest that silicone augmentation of the
      breast is not associated with an increased risk of mammary carcinoma, cases of
      breast carcinoma arising in augmented breasts are being increasingly encountered
      as a large number of patients who had augmentation are getting older. A case of a
      51-year-old woman with a 20-year history of breast augmentation who developed an
      invasive cribriform carcinoma associated with extensive microcalcification is
      presented. The patient had submammary silicone implants 20 years ago that were
      replaced, because of local complications, in subpectoral positions 10 years
      later. Dispersive X-ray microanalysis failed to demonstrate silicone in sections
      of the tumor and adjacent breast tissue. Appropriately fixed tumor tissue was
      available for electron microscopic examination. The tumor cells were rich in
      mitochondria, and their luminal surfaces were endowed with abundant microvilli,
      but the cell surfaces that came closest to the calcified microspheriols were
      devoid of microvilli and had cellular buddings between the microspheriols. It is
      suggested that the tumor cells might have been actively involved in the process
      of microcalcification.

PMID- 7810004
TI  - Case for the panel. Unusual ultrastructural finding.

PMID- 7810005
TI  - [Functional image diagnosis--physiology and biochemistry].

PMID- 7810007
TI  - [Magnetic resonance imaging of disseminated sclerosis].
AB  - Multiple sclerosis is a chronic demyelinating disease. Paraclinical examinations
      may contribute to the diagnosis of multiple sclerosis. Magnetic resonance imaging
      (MRI) has a very high sensitivity concerning multiple sclerosis, and has made it
      possible to visualize multiple sclerosis plaques in vivo, to follow each plaque
      over the course of time and in this way to obtain information about the
      pathogenesis. MRI has shown that the size of plaques may vary considerably, and
      that plaques are dynamic structures with the ability to change in size over few
      weeks. By using MRI and the contrast agent Gadolinium-DTPA, it is possible to
      distinguish a newly developed plaque from an older one. Therefore, MRI has become
      an important examination in therapeutic trials. Just now, MRI with Gadolinium
      DTPA is being used to evaluate the efficacy of plasmapheresis and immunoglobulin
      treatment in a joint study between Rigshospitalet and Hvidovre Hospital.

PMID- 7810008
TI  - [New therapeutic possibilities for disseminated sclerosis?].
AB  - Multiple sclerosis is a demyelinating disease of unknown origin. Immunological
      processes are thought to be of pathophysiological importance. Immunosuppressive
      treatment has been tried with various drugs in order to influence the
      immunological process. Steroid hormones are able to reduce the duration of an
      acute attack, but have no influence on the long-term progression.
      Cyclophosphamide can reduce disease activity a little, but has severe side
      effects. Azathioprine may reduce the frequency of acute attacks and disease
      progression a little. Cyclosporine A in the treatment of multiple sclerosis is
      only effective in doses so high that the side effects are unacceptable.
      Plasmapheresis in combination with immunosuppressive treatment is shown to
      stabilize the disease in some experiments. Intravenous polyclonal immunoglobulin
      has shown promising results in the treatment of other immunologically based
      diseases, and is a potentially beneficial treatment in multiple sclerosis. At
      Rigshospitalet, ongoing clinical trials will evaluate the efficacy of
      plasmapheresis and polyclonal immunoglobulin.

PMID- 7810006
TI  - [Positron emission tomography. A new measurement method for imaging of regional
      and biochemical parameters].
AB  - Positron emission tomography (PET) is a method for quantitative imaging of
      regional physiological and biochemical parameters. Positron emitting radioactive
      isotopes can be produced by a cyclotron, eg. the biologically important carbon
      (11C), oxygen (15O), and nitrogen (13N) elements. With the tomographic principle
      of the PET scanner the quantitative distribution of the administered isotopes can
      be determined and images can be provided as well as dynamic information on blood
      flow, metabolism and receptor function. In neurology PET has been used for
      investigations on numerous physiological processes in the brain: circulation,
      metabolism and receptor studies. In Parkinson's disease PET studies have been
      able to localize the pathology specifically, and in early stroke PET technique
      can outline focal areas with living but non-functioning cells, and this could
      make it possible to intervene in this early state. With positron emission
      tomography a quantitative evaluation of myocardial blood flow, glucose and fatty
      acid metabolism can be made as well as combined assessments of blood flow and
      metabolism. Combined studies of blood flow and metabolism can determine whether
      myocardial segments with abnormal motility consist of necrotic or viable tissue,
      thereby delineating effects of revascularisation. In the future it will probably
      be possible to characterize the myocardial receptor status in different cardiac
      diseases. The PET technique is used in oncology for clinical as well as more
      basic research on tumor perfusion and metabolism. Further, tumor uptake of
      positron labelled cytotoxic drugs might predict the clinical benefit of
      treatment.

PMID- 7810009
TI  - [Pregnancy and sick leave].
AB  - The literature indicates a high percentage of sick leave during pregnancy in the
      past 10 years. In the Nordic countries 30-50 percent of pregnant women on the
      labour market are on sick leave during pregnancy. There is no indication that the
      increased frequency is due to decreased health amongst pregnant women, but it may
      be a consequence of an increase in working women. Pregnancy means additional
      strain to the double tasks that many working women experience. A few references
      indicate that sick leave is most common among women working full time and women,
      who have previously given birth. Sick leave may cover up for increasingly poor
      working environments or social problems, but may also reflect changes in
      standards, legislation or role performance. It is advisable to follow pregnant
      women on sick leave closely in order to avoid expulsion from the labour market.
      Pregnancy-related sick leave seems to be multifactorial, which should lead to
      caution concerning conclusions on the relative influence of different factors on
      sick leave during pregnancy.

PMID- 7810010
TI  - [Ophthalmological services to mentally retarded persons. A review and
      recommendations].
AB  - This is a survey of Nordic contributions to the study of the development of
      vision, visual impairment, and ocular disorders in people with developmental
      delay. Visual impairment and ocular pathology are frequently observed in these
      individuals. We give examples of various combinations of ocular and cerebral
      disorders. We underline the central role of the ophthalmologist in the
      diagnostic, therapeutic, and counselling procedures, and stress that the quality
      and accessibility of eye health services have definite medical, educational and
      social consequences for this group of people. We suggest that our countries
      monitor vision and eye disease in all individuals with developmental delay at the
      following periods of life: 1) At the first assessment of developmental delay. 2)
      At 2-3 years of age. 3) At the beginning and end of school. 4) At 45 years of age
      and every five years thereafter. 5) People with Down's syndrome should be
      monitored for cataract at the ages of one month, one year, 30 years, and later as
      the rest of the patients.

PMID- 7810011
TI  - [Results of hearing preservation via middle fossa approach in surgery for
      acoustic neurinoma].
AB  - The results of hearing preservation surgery in a series of 10 patients with 10
      unilateral acoustic neuromas are reported. Mortality was 0%, complications
      including rhinoliquorrhoea occurred in 10%, and the tumour was removed in 100%.
      Hearing preservation was obtained in 80%. Normal or nearly normal postoperative
      facial nerve function evaluated one year after surgery was achieved in all cases.
      According to House-Brackmann classification, 60% had HB-1 and 40% had HB-2. The
      fact that no audiovestibular or electrophysiological examinations are specific
      for acoustic neuroma can not be overemphasized. Early diagnosis of these small
      tumors in patients with good hearing has made this kind of surgery possible.

PMID- 7810012
TI  - [Scaphoid fractures. Fracture types and localization].
AB  - The incidence, localization, and type of scaphoid fractures found in a well
      defined population is described. Fractures of the carpal scaphoid (n = 442) of
      which 19 (5%) were nonunions were identified during an eight-year period. Among
      inhabitants living in the Odense Municipality (population at risk 170,648 in 1983
      to 174,948 in 1989) 222 males and 51 females who sustained scaphoid fractures
      during a seven-year period were used for computation of incidence. During the
      survey, there was an average annual incidence of scaphoid fracture of eight per
      100,000 females, and 38 per 100,000 males. The average annual incidence per
      100,000 inhabitants of carpal scaphoid fractures according to the location was
      proximal two, middle 15, and distal six. Average annual incidence per 100,000
      inhabitants of carpal scaphoid fractures according to type was transverse seven,
      horizontal oblique nine, vertical oblique one, avulsion/fracture of the
      tuberosity five, and not stated one.

PMID- 7810013
TI  - [Gentamycin resistant Enterobacteriaceae at a neonatal care unit].
AB  - A case of septicaemia in a seven-day-old infant with a gentamicin-resistant
      strain of Enterobacter cloacae prompted an epidemiological survey in a neonatal
      unit. Another 18 patients harboured gentamicin-resistant Enterobacteriaceae
      without symptoms. Control of the outbreak was achieved by cohort nursing, strict
      hygiene and reduction of aminoglycoside consumption by 50%. Efficiency of the
      measures was monitored by weekly faecal samples from all patients. All strains
      produced the aminoglycoside modifying enzyme AAC(3)II. The resistance was plasmid
      mediated.

PMID- 7810014
TI  - [Treatment of acute myeloid leukemia in the elderly with low-dose cytosine
      arabinoside].
AB  - We report the outcome of 95 patients older than 60 years with de novo acute non
      lymphocytic leukaemia (ANLL), treated in two institutions during a 10 year
      period. Thirty-two patients, mean age 78 years, did not receive any chemotherapy,
      and their median survival was 38 days. Five patients in good clinical condition,
      aged 60-63 years, were treated conventionally with an anthracycline and
      cytarabine, and three patients obtained a complete remission (CR) lasting 73,
      417, and 1050 days. Fifty-eight patients were treated with low-dose cytarabine
      (LDC) for remission-induction and maintenance. Eighteen patients obtained CR,
      yielding a remission rate of 31%. The median duration of remission was 380 days
      and median survival of the same group was 498 days. LDC is valuable in the
      treatment of ANLL in the elderly. Controlled studies are warranted to define the
      indications for LDC versus conventional therapy in the large grey zone of elderly
      patients.

PMID- 7810015
TI  - [Budesonide in the treatment of mild asthma. A placebo-controlled multicenter
      study in general practice].
AB  - Fifty patients with mild asthma were randomized in a double-blind, parallel group
      design; 13 were protocol violators. Of the remaining 37, 20 patients were treated
      with budesonide, 17 with placebo. The Peak Expiratory Flow rate (PEF) was the
      main variable. In a diary, patients recorded PEF morning and evening, score of
      asthma symptoms and use of inhaled beta 2-agonist. Peak-flow and Goldberg's
      General Health Questionnaire were obtained at clinic visits. Parametric and non
      parametric tests were used. All tests were two-tailed with a significance level
      of 0.05. The study proved that changes in the patients' PEF happened in the early
      phase of the treatment period. The increase in both morning and evening PEF and
      physical activity in the budesonide group were statistically significantly better
      than in the placebo group. There was no statistical difference between the two
      groups concerning the patients' general well-being as evaluated by Goldberg's
      General Health Questionnaire. No serious adverse events occurred. The conclusion
      is that patients with mild asthma had statistically significant effect on their
      morning and evening PEF and physical activity from treatment with a daily dose of
      400 microgrammes budesonide given via Turbuhaler compared to treatment with
      placebo.

PMID- 7810016
TI  - [Significance of fatty acid composition in plasma and in food for cellular immune
      function in elderly men].
AB  - The relation between fatty acid composition in plasma and natural killer (NK)
      cell activity and the relation between fatty acid composition of diet and NK cell
      activity was evaluated in healthy elderly men. The correlations between basal NK
      activity and the fraction of plasma fatty acids consisting of total
      polyunsaturated fatty acids (PUFA), total n-6 fatty acids and linoleic acid were
      r = -0.68, p = 0.006, r = 0.62, p = 0.014 and r = 0.52, p = 0.048, respectively.
      Significant negative correlations were also found between alpha-interferon
      stimulated NK cell activity and the three groups of fatty acids and between
      interleukin-2 stimulated NK cell activity and PUFA. Likewise, negative
      correlations between grammes of PUFA in diet, determined from two four-day
      registration-periods, and basal NK and alpha-interferon stimulated NK cell
      activity were found. No significant negative correlation between percentage
      intake of n-3 fatty acids and NK cell activity was found. It is concluded that
      the type of dietary fatty acids influence NK cell activity in elderly men. A high
      intake of n-6 polyunsaturated fatty acids may be detrimental to cellular immune
      defence mechanisms in the elderly.

PMID- 7810018
TI  - [Intracranial venous thrombosis].

PMID- 7810017
TI  - [Nephropathia epidemica. Hantavirus nephritis--a differential diagnosis in acute
      abdomen].
AB  - Nephropathia epidemica (NE) is an infectious disease caused by hantavirus of the
      Bunyavirus family and carried by little rodents, in Denmark presumably by the
      bank vole (Clethrionomys glareolus). The disease usually presents with self
      limiting renal failure, thrombocytopenia, fever, lower back and/or abdominal
      pain. As such it might be confused with for example acute abdomen as shown by the
      two cases given. Final diagnosis is based upon demonstrating antibody formation
      against hantavirus.

PMID- 7810019
TI  - Introduction to special issue in honor of John M. Reid.

PMID- 7810020
TI  - On the spectral properties of Doppler thread phantoms.
AB  - It is shown that some of the threads used in Doppler phantoms have a repetitive
      structure which leads to peaks in the angular distribution of the backscattered
      power at beam axis-to-flow angles of theta = 90 degrees and approximately theta =
      70 degrees. This nonuniform scattering does not significantly interfere with
      modelling the Doppler spectrum peak as a function of velocity and beam-to-thread
      angle, but makes it impossible to model the spectral width as a function of these
      parameters. A new plaited structure is described which has a periodicity too
      small to lead to subsidiary reflection peaks, and which has a more uniform
      backscattering profile than the other threads studied.

PMID- 7810021
TI  - Prediction of ultrasonic field propagation through layered media using the
      extended angular spectrum method.
AB  - The angular spectrum method is a powerful technique for modeling the propagation
      of acoustic fields. The technique can predict an acoustic pressure field
      distribution over a plane, based upon knowledge of the pressure field
      distribution at a parallel plane. Predictions in both the forward and backward
      propagation directions are possible. In addition to predicting the effects of
      diffraction, the model also includes the effects of attenuation, refraction,
      dispersion, phase distortion, and the effects of finite amplitude acoustic
      propagation. No other model currently exists which can predict the propagation of
      wideband acoustic fields produced by sources of arbitrary geometry including all
      of the above propagation effects. Prior investigations have focused on using
      backward propagation predictions to analyze the surface vibration patterns of
      acoustic radiators. In contrast, the current effort has placed particular
      emphasis on verifying the model in the forward propagation case. In this paper,
      both forward and backward predictions are presented which demonstrate the ability
      of the model to characterize a three-dimensional acoustic field based upon
      measurements at a single plane. Results are also presented which examine the
      ability of the extended model to predict acoustic propagation through media
      composed of stacked homogeneous layers. The model has immediate applications in
      the study of acoustic phenomena and in the field of acoustic transducer design.
      Additionally, significant progress has been made toward the ultimate goal of
      predicting the degradation of acoustic transducer performance due to propagation
      through inhomogeneous, nonlinear, tissue-like media.

PMID- 7810022
TI  - Analysis of ultrasonic scattering in blood via a continuum approach.
AB  - Since the pioneering work by Reid et al. on measuring ultrasonic scattering in
      blood, this phenomenon has been extensively studied both theoretically and
      experimentally. The knowledge on ultrasonic scattering properties of blood is
      needed for the design of ultrasonic methods for measuring blood flow, and a
      better interpretation of ultrasonic images. The development of high frequency
      intravascular or intracardiac imaging devices raises the possibility of measuring
      blood properties, e.g., erythrocyte aggregation and fibrinogen concentration, in
      situ. A number of theoretical approaches have been developed to analyze this
      phenomenon where in general ultrasound wavelength is much greater than the
      erythrocytes. These results show that the backscattering coefficient of blood,
      defined as power backscattered by a unit volume of blood per steradian per unit
      incident intensity, is proportional to variance of the erythrocyte number
      fluctuation and backscattering cross-section of a single erythrocyte. In this
      paper, we will show that similar results can also be obtained by taking a
      continuum approach.

PMID- 7810023
TI  - Comparison of the performance of three maximum Doppler frequency estimators
      coupled with different spectral estimation methods.
AB  - The performance of three spectral techniques (FFT, AR Burg and ARMA) for maximum
      frequency estimation of the Doppler spectra is described. Different definitions
      of fmax were used: frequency at which spectral power decreases down to 0.1 of its
      maximum value, modified threshold crossing method (MTCM) and novel geometrical
      method. "Goodness" and efficiency of estimators were determined by calculating
      the bias and the standard deviation of the estimated maximum frequency of the
      simulated Doppler spectra with known statistics. The power of analysed signals
      was assumed to have the exponential distribution function. The SNR ratios were
      changed over the range from 0 to 20 dB. Different spectrum envelopes were
      generated. A Gaussian envelope approximated narrow band spectral processes (P. W.
      Doppler) and rectangular spectra were used to simulate a parabolic flow
      insonified with C. W. Doppler. The simulated signals were generated out of 3072
      point records with sampling frequency of 20 kHz. The AR and ARMA models order
      selections were done independently according to Akaike Information Criterion
      (AIC) and Singular Value Decomposition (SVD). It was found that the ARMA model,
      computed according to SVD criterion, had the best overall performance and
      produced results with the smallest bias and standard deviation. In general
      AR(SVD) was better than AR(AIC). The geometrical method of fmax estimation was
      found to be more accurate than other tested methods, especially for narrow band
      signals.

PMID- 7810024
TI  - History of medical and biological ultrasound at the University of Pennsylvania.
AB  - We briefly review my early contacts with bioacoustics and the bioacoustic work at
      the University of Pennsylvania that took place from the early 1950s to 1975. It
      was carried out with E. L. Carstensen, K. Li, A. Smith, H. Pauly, J. Reid, P.
      Edmonds and many students. The emphasis was first on basic biophysical studies.
      The work with E. Carstensen and H. Pauly was primarily concerned with the
      mechanism causing the high absorption typical for tissues and cell suspensions.
      Macromolecular content was shown to be largely responsible for the absorption.
      Practical applications concerned the relative merits of electromagnetic and
      ultrasonic diathermy techniques. P. Edmonds extended the range of macromolecular
      studies to 100 MHz and initiated work on the attenuation in lung tissues. After
      J. Reid came to Pennsylvania, the development of echocardiography took place.

PMID- 7810025
TI  - Characterization of ultrasonic transducers using a fiberoptic sensor.
AB  - The PVDF (polyvinylidene fluoride) hydrophones, commonly used to measure the
      characteristics of ultrasonic transducers, suffer from a number of drawbacks.
      They disturb the field distribution to be measured and cause spatial averaging
      effects because of their finite aperture. In addition, they are very delicate and
      susceptible to damage. To overcome some of these problems, the authors previously
      proposed the use of an optical fiber-based probe to measure the ultrasonic
      fields. In this paper, this fiberoptic ultrasonic sensor is used to measure the
      characteristics of six transducers, focused as well as unfocused, covering a
      frequency range of 2.25 MHz to 20 MHz. Results obtained using the fiberoptic
      sensor are compared with those obtained using a calibrated PVDF needle hydrophone
      with an effective diameter of 0.5 mm. The temporal responses as well as the beam
      profiles of the transducers measured using the fiberoptic sensor show excellent
      agreement with the results obtained using the PVDF needle hydrophone.

PMID- 7810026
TI  - Ultrasonic Doppler detection of laser-tissue interaction.
AB  - Laser therapy for the safe and effective coagulation and ablation of tissues
      requires precise control of the amount of energy delivered to and absorbed by the
      volume of tissue of interest. We propose that an ultrasonic transducer pointing
      in the same direction as the laser fiber could be used to monitor the changes in
      ultrasonic properties caused by the absorption of light by the tissue. A modified
      20 MHz pulsed Doppler was used to evaluate the ultrasonic effects of 35 exposures
      of beef liver and muscle to a high power diode laser in vitro in real time. We
      found two distinct levels of acoustic activity in the tissue. Type 1 activity
      consisted of slow variations in the phase and small changes in the amplitude of
      the echoes, while type 2 activity consisted of large and rapid fluctuations in
      amplitude and phase. We found that the residual increase in echogenicity of the
      tissue and the delay to the onset of type 2 activity were functions of laser
      power and tissue type and were correlated to lesion severity. We hypothesize that
      type 1 activity corresponds to motion (thermal expansion and contraction) of the
      tissue, and that type 2 activity corresponds to the creation of gas bubbles
      (vaporization) in the tissue. We conclude that the absorption of energy changes
      the acoustic properties of tissue during and after exposure and that Doppler
      signal processing can be used to differentiate various levels of laser-tissue
      interaction in real time.

PMID- 7810027
TI  - Hodgkin's disease in young and elderly patients. Clinical and pathological
      studies. Minireview based on a doctoral thesis.

PMID- 7810028
TI  - Phosphoprotein patterns in Onchocerca volvulus developmental stages.
AB  - Living females and microfilariae of Onchocerca volvulus incubated in culture
      medium containing [32P]orthophosphate were observed to phosphorylate their
      proteins rapidly. Patterns of phosphoproteins in extracts from these labelled
      parasites were compared after two dimensional electrophoresis and
      autoradiography. Protein extracts from eggs, microfilariae and adult females of
      O. volvulus were phosphorylated in the presence of [gamma-32P]ATP, magnesium
      acetate, and added cyclic AMP-dependent protein kinase or the endogenous protein
      kinase present in the extracts. Patterns of phosphoproteins were compared after
      separation by single and two-dimensional gel electrophoresis followed by
      autoradiography. Common phosphopeptide bands were observed when phosphorylated
      extracts from adult females, microfilariae and eggs were compared. However,
      extracts from eggs displayed unique phosphorylated polypeptides of M(r) 30,000
      and 34,000 that were absent from the extracts from microfilariae. Furthermore,
      two phosphorylated polypeptides of M(r) 47,000 and 76,000 were detected in
      extracts from microfilariae but not from eggs. These results indicate that O.
      volvulus parasites may phosphorylate different proteins at different stages of
      their development.

PMID- 7810029
TI  - Estimation of aerobic and anaerobic metabolism in isometric forearm exercise.
AB  - The aim was to evaluate the energy turnover in the forearm during isometric
      submaximal exercise. Eight subjects performed isometric handgrip contractions
      until exhaustion at 10%, 25% and 40% of maximal voluntary contraction (MVC).
      Blood samples were drawn frequently from the cubital vein of the exercising arm
      during exercise and a 60 minutes recovery period, and forearm blood flow
      (plethysmography) was monitored during the same periods. Oxygen uptake and
      lactate release were used to quantify aerobic and anaerobic energy expenditure.
      Electromyography (frequency analysis) was monitored during exercise. Anaerobic
      glycolysis contributed 4%, 31% and 37% of the ATP production in the three
      experiments, respectively, but total ATP production from anaerobic glycolysis was
      the same, suggesting a maximal anaerobic glycolytic capacity (MAGC). MAGC may be
      a limiting factor for muscle performance at 25 and 40% MVC, but not at 10% MVC.
      Judging from the match between oxygen debt or estimated oxygen deficit vs the
      anaerobic energy production, the muscles recovered during 60 min rest after 10%
      MVC and 40% MVC. However, recovery after 25% MVC may have been incomplete.

PMID- 7810030
TI  - Dermatoglyphics in individuals with asocial behaviour.
AB  - The patterns of fingertip prints (dermatoglyphics) in Swedish series of sexual
      offenders of law compared with common offenders of law and normal individuals
      were analysed. The dermatoglyphic patterns in common offenders of law did not
      differ from those in normal individuals. The group of sexual offenders of law
      showed statistically significant differences (p < 0.001) in the dermatoglyphic
      patterns compared to the samples of common criminals and normals.

PMID- 7810031
TI  - Neonatal polycythaemia in Down syndrome (short communication).

PMID- 7810033
TI  - [Scleral compression in assessment of the stage of proliferative
      vitreoretinopathy and type of subretinal contents in retinal detachment].
AB  - The authors analyse intraocular changes occurring in detachment of the retina
      using sclero-compression data. A total of 447 eyes of 417 patients with
      detachment of the retina complicated by proliferative vitreoretinopathy of
      various severity were examined. Four main types of compression chorioretinal
      relationships are distinguished permitting a preoperative differential diagnosis
      of stages of concomitant proliferative vitreoretinopathies and of the type of
      subretinal contents in detachment of the retina. The diagnosis of proliferative
      vitreoretinopathy in detachment of the retina is based on international
      classification, though it does not fully reflect all specific features of the
      disease. Basing on the data of analysis of compression chorioretinal
      relationships, the authors supplement the known classification as regards the
      interpretation of the minimal stage A which is considered more extensively and
      the moderate stage B of proliferative vitreoretinopathy. The described assessment
      of intraocular changes in detachment of the retina permits not only a correction
      of the routine assessment of stages of this condition, but is practically
      valuable. The authors suggest four basic approaches to the choice of the optimal
      surgical strategy, based on the disease characteristics, stage of proliferative
      vitreoretinopathy, and type of compression chorioretinal relationships.

PMID- 7810032
TI  - [Ophthalmological symptoms of visual tract lesions in craniocerebral injuries].
AB  - Craniocerebral injuries are known to involve the visual tract in 2-5% of cases.
      Fifty-nine patients aged 5 to 68 with visual tract involvement in craniocerebral
      injury were examined in N. N. Burdenko Institute of Neurosurgery of the Russian
      Academy of Medical Sciences. Unilateral optic nerve involvement was found in 48
      patients, involvement of the chiasm and/or both optic nerves in 11. Involvement
      of a single optic nerve was associated with vision acuity reduction, 30 patients
      becoming blind or virtually blind, and with various defects of the visual field.
      Traumatic injury to the chiasm manifested as a rule by the asymmetric chiasmal
      syndrome. Follow-up of the patients in the acute period of craniocerebral injury
      showed that paling of the optic disc manifested in various periods after the
      moment of the injury, from 3-4 days to 1 month, this depending on the
      localization of the injury and its distance from the posterior pole of the eye.
      Besides visual disturbances and ophthalmoscopic changes, oculomotor disorders
      were found which were caused by traumatic impairment of the oculomotor nerves (in
      the orbit or skull) and muscles. Transcutaneous electrostimulation of the injured
      optic nerves was sufficiently effective, its efficacy directly depending on the
      period elapsed since the injury, excepting blind or virtually blind patients.

PMID- 7810034
TI  - [Physiological requirements of spectral characteristics of contact lenses in
      correction of aphakia in young children].

PMID- 7810035
TI  - [Use of low-energy laser irradiation in patients with progressive myopia].
AB  - A method of infrared laser exposure at a wavelength 1.3 microns for the treatment
      of progressive myopia has been developed, permitting a contactless trans-scleral
      irradiation of the ciliary muscle. Laser stimulation was carried out in 117
      patients (234 eyes) aged 7 to 16. By the end of the first follow-up year the mean
      values of the positive part of accommodation increased by 2.0 to 2.5 diopters in
      patients of all age groups. A reduction of the parameters of ocular function was
      recorded 6-12 months after laser stimulation, though they remained higher than
      initially. A repeated curse of therapy helped normalize accommodation reserve
      parameters again. Prestimulation rheographic coefficient in all the examinees was
      2.7 +/- 0.03% on an average, after treatment it was 3.44 +/- 0.02%. Hence,
      ciliary muscle stimulation by infrared laser helps in the majority of cases
      stabilize clinical refraction.

PMID- 7810036
TI  - [Accommodation].
AB  - Based on the literature data and his own findings the author makes an attempt to
      specify the accommodation mechanism, particularly hyaloid effect on the lens in
      the course of accommodation. It is believed, and the author presents experimental
      data in favor of this assumption, that in youth the lens and hyaloid represent a
      single optic complex. The lens sealed in the cup-like depression of the vitreous
      body cannot be mobile in relation to the hyaloid and cannot acquire a more convex
      shape by itself at the height of accommodation. Moreover, experiments have proved
      that at the height of accommodation, according to many authors' data, the
      posterior pole of the lens is shifted towards the hyaloid to a distance of 0.16
      to 0.27 mm, which the lens surely cannot do by itself. The hyaloid making
      rotatory movements at the height of accommodation, it is evident that the lens in
      this case passively follows the hyaloid and acquires an aspherical shape only
      under its effect. The ciliary belt plays but a secondary role in this process,
      being just a buffer.

PMID- 7810037
TI  - [Clinical-immunological disorders in uveitis in patients with Behcet's syndrome].
AB  - The results of comprehensive clinicoimmunologic examinations of 38 uveitis
      patients with Behcet's disease indicate that uveitis in the presence of Behcet's
      disease should be referred to multifactorial diseases to whose pathogenesis
      immunopathologic reactions in various combinations and genetic predisposition
      contribute much. Generalization of the process in the eye predominated in the
      clinical picture with involvement of the anterior and posterior segments, retinal
      vessels, this being combined with general somatic symptoms (aphthae on the buccal
      mucosa, genitals, arthritides, urethritis/cystitis symptoms, positive 'pricking'
      test). Study of the immunity status revealed depressed lymphocyte proliferative
      response to mitogen in 58.8% of patients, hyperimmunoglobulinemia of the A and M
      classes in 63.3%, impaired complex formation (increased levels of circulating
      immune complexes in 78.3% and cryoglobulin presence in 57.1%), and various
      combinations of these immunologic signs. The results indicated patients'
      infection with herpes virus, streptococcus, toxoplasma. An associative connection
      of Behcet's disease with A (II) red cell phenotype in 54.8% of patients (p <
      0.05) suggests a relationship between genetic factors and the conditions of a
      specific geographic region. A variety of immunologic changes necessitated the use
      of corticosteroids, hemoperfusion, cytostatics, and immunity stimulants in the
      treatment of uveitis in Behcet's disease patients.

PMID- 7810038
TI  - [Studies on ocular rigidity].
AB  - An ophthalmo-sphygmographic method for assessment of ocular rigidity is
      suggested. Rigidity coefficient E is estimated from changes in intraocular
      pressure and eye volume connected with systolic increment of blood volume. The
      mean E value in normal subjects (n = 123) was 0.0214 +/- 0.005. The results of
      the suggested method for E coefficient assessment and Friedenwald's method were
      in good correlation (r = 0.72). Use of Schiotz's constant weight impression
      sensor helped do without differential tonometry and therefore simplify the method
      and rule out the errors typical of the traditional methods.

PMID- 7810039
TI  - [Late results of pathogenetically-oriented surgical treatment in congenital
      glaucoma and problems of medical rehabilitation].
AB  - Results of pathogenetical surgical treatment of congenital glaucoma were analyzed
      in late periods after surgery, from 1 to 17 years, in 105 patients (171 eyes).
      Ophthalmic tone normalization was attained in 87.5% of cases. High vision acuity
      was retained in 57.7% of cases. The principal causes of reduced central vision in
      process stabilization were astigmatism in 61.7%, amblyopia in 71.5%, strabismus
      in 59%, anisometropia in 22.8%. To improve vision acuity computer-aided pleoptic
      treatment was carried out in the postoperative period in 42 children (76 eyes).
      The efficacy of the method was 84.2%.

PMID- 7810040
TI  - [Electrophysiological and neuroradiological methods in the diagnosis and
      prognostication of functional outcome in young children with lesions of the
      visual tract].
AB  - The authors analyze the data of computer-aided tomography, neurosonography, and
      visual evoked potentials to chess pattern reversal in 14 infants aged 6 to 11
      months with partial atrophy of the optic nerve and/or visual cortex involvement
      before and in various periods after transcutaneous electric stimulation combined
      with neurotrophic drug therapy. The advantages of comprehensive examinations in
      neuroophthalmological diagnosis in infants are shown, as is the possibility of
      using electrophysiological and neuroradiological methods for prediction of
      functional outcomes in the said patient population.

PMID- 7810041
TI  - [Study of changes in the central visual field in early computer-assisted
      diagnosis of primary open-angle glaucoma].
AB  - The authors analyze the value of automated static perimetry for the early
      diagnosis of glaucoma. A total of 232 patients were examined, in 74 of them with
      primary open-angle glaucoma belonging to two age groups a reliable reduction was
      revealed of the mean retinal light sensitivity (p < 0.0001 vs. control and in
      suspected glaucoma in subgroups 1 and 2 p < 0.0001 and p < 0.01, respectively).
      Diffuse and local depression of light sensitivity in the central visual field was
      found in glaucoma patients and subjects with the condition suspected. Kinetic
      perimetry revealed narrowing of the peripheral borders of the visual field in 20%
      of glaucoma patients.

PMID- 7810042
TI  - [Refractive interlamellar keratoplasty with an explant].

PMID- 7810043
TI  - [Diagnosis and care of patients with albinism].

PMID- 7810044
TI  - [An experimental-clinical study of the effectiveness of kerakol in the treatment
      of corneal burns and mechanical injuries ].
AB  - Kerakol efficacy in experimental burn and mechanical injuries was studied. The
      drug was shown to stimulate repair processes in the cornea, promoting an earlier
      differentiation of epithelial cells and their layers. Corneal stroma repair
      manifested by an earlier maturation of collagen structures with their correct
      orientation. Clinical trials showed kerakol efficacy in the treatment of corneal
      burns and injuries.

PMID- 7810045
TI  - [Specific features of war injuries of the eyes in peace time].
AB  - The authors analyze clinical features of injuries to the organ of vision under
      extreme conditions of a local war conflict and present their recommendations on
      rehabilitation of the victims. The status of 203 patients with eyeball wounds
      inflicted under such conditions is analyzed. To optimize the outcomes of war
      traumas to the eye inflicted in peace time the authors give the following
      recommendations based on the specific features of such injuries and the objective
      conditions in foci of regional conflicts: (1) Rapid evacuation of wounded
      subjects to the nearest ophthalmological institutions; (2) Maximally early
      primary ophthalmological care with obligatory primary surgical debridement of the
      wound; (3) No attempts at removal of a foreign body during primary surgical
      debridement at local medical institutions; (4) the earliest possible evacuation
      of the victims after wound debridement to specialized ophthalmo-traumatological
      institutions for further rehabilitation.

PMID- 7810046
TI  - Equine salmonellosis in a Dutch veterinary teaching hospital.
AB  - During 1990 and 1991, 380 faecal samples were collected from horses with
      diarrhoea. Sixty-nine (18 per cent) of the samples yielded a positive culture for
      Salmonella species, and salmonellae were cultured directly from 37 (54 per cent)
      of these cases. In 32 (46 per cent) of the cases the salmonellae were found after
      culturing the organism in an enrichment medium. Salmonella typhimurium was
      isolated from 43 samples, S hadar from three samples, S arizona from two, S
      enteritidis from two, S virchow from one, S blockley from one and S bareilly from
      one sample. In 1990, S typhimurium phage type 200 was the predominant phage type,
      whereas in 1991 phage types 510, 656 and 658 were encountered most often. The
      antibiotic susceptibility of 53 of the 69 isolates was assessed and 28 of them
      were resistant to more than three antimicrobial agents. Resistance to
      streptomycin and the tetracyclines was common, but most of the isolates were
      sensitive to gentamicin and nitrofurantoin.

PMID- 7810047
TI  - Behaviour of dairy cows in a straw yard in relation to lameness.
AB  - Lying down and other behavioural activities of dairy cows were studied for three
      24-hour periods in a straw yard. The cows spent a total of 13.6 hours in the
      straw yard and lay down for 9.7 hours. The lying down time in one observation was
      10.8 hours and this period may be considered ideal because there was little
      disturbance during that observation. Significantly more time was spent lying down
      at night than in the day and significantly more time was spent lying down and
      ruminating than standing up and ruminating. The total time spent lying down was
      significantly positively correlated with the time spent lying down and
      ruminating. Ten hours or more spent lying down may be adequate for proper rest in
      dairy cattle. Straw yards are better than many cubicles for lying and a longer
      period spent lying down may be important for the prevention of lameness in dairy
      cows.

PMID- 7810048
TI  - Brucella ovis infection in two flocks of sheep.
AB  - Brucella ovis infection could not be eradicated from two flocks of sheep despite
      serologically testing and culling the infected rams for four years. The
      hypothesis that the ewes played a major role in the maintenance of the infection
      in both flocks was investigated by using serological, bacteriological and
      pathological criteria. Specific antibodies against B ovis were demonstrated in 71
      ewes in the two flocks. Forty-four of the seropositive ewes were slaughtered for
      bacteriological and pathological studies and B ovis was isolated from 16 of them;
      the uterus was the target organ of the infection, although extrauterine infection
      was also demonstrated in some of the infected ewes.

PMID- 7810049
TI  - Effect of the method of stunning and the interval between stunning and neck
      cutting on blood loss in turkeys.
AB  - Turkey hens were stunned by inducing anoxia with either argon (with approximately
      2 per cent residual oxygen) or 30 per cent carbon dioxide in argon with 2 per
      cent residual oxygen, and the carcases were bled either immediately or five or 10
      minutes after they had been stunned. A control group of turkeys was stunned
      electrically (250 mA for about four seconds) and had their necks cut immediately
      after stunning. The amount of blood lost was measured and expressed as a
      percentage of liveweight. The results showed that the necks of gas-stunned
      turkeys can be cut up to 10 minutes after they have been stunned without reducing
      the total blood loss significantly.

PMID- 7810050
TI  - Isolation of Mycoplasma bovis from a calf imported into the Republic of Ireland.

PMID- 7810051
TI  - Fluorosis in buffaloes.

PMID- 7810052
TI  - Rabies policy.

PMID- 7810053
TI  - Rabies policy.

PMID- 7810054
TI  - Sebaceous adenitis in the standard poodle.

PMID- 7810055
TI  - Unusual case of malignant catarrhal fever.

PMID- 7810056
TI  - Use of ELISAs for the diagnosis of canine atopy.

PMID- 7810057
TI  - Proteins induced by recombinant equine interferon-beta 1 within equine peripheral
      blood mononuclear cells and polymorphonuclear neutrophilic granulocytes.
AB  - Peripheral blood mononuclear cells (PBMC) and polymorphonuclear neutrophilic
      granulocytes (PMN) as well as embryonic equine dermal fibroblasts and the equine
      fibroblast line E. Derm which were used as controls, were treated with
      recombinant equine interferon-beta 1 (rEqIFN-beta 1) in vitro which induced the
      expression of different proteins in these cells. A 74 kDa protein was induced in
      PBMC and an 82 kDa protein was additionally found in the equine fibroblast E.
      Derm cell line following treatment with rEqFN-beta 1. Both proteins reacted with
      anti-mouse and anti-human Mx protein antisera in immunoblot tests. The 74 kDa and
      perhaps the 82 kDa components may thus represent equine 'Mxanalogous proteins'.
      The 74 kDa protein was only detected in PBMC of ten out of 20 horses examined.
      The induction of Mx protein in the horse by Type 1 interferon may therefore
      resemble that in the mouse, where Mx protein is involved in selective resistance
      to influenza virus. The influence of rEqIFN-beta 1 on protein expression in
      equine PBMC and PMN was monitored by metabolic labeling and 2-D gel
      electrophoresis. Proteins of 82, 74, 58 and 40 kDa were induced in PBMC following
      exposure to rEqIFN-beta 1. A constitutively expressed 35 kDa protein, however,
      was no longer demonstrable upon treatment with interferon. None of the proteins
      induced within PBMC was found in highly purified PMN treated with interferon. PMN
      exposed to rEqIFN-beta 1 synthesized four proteins in the range of 25 to 27 kDa.
      These proteins have not been described in interferon-treated PMN of any other
      species.

PMID- 7810058
TI  - Caprine arthritis-encephalitis lentivirus (CAEV) challenge of goats immunized
      with recombinant vaccinia virus expressing CAEV surface and transmembrane
      envelope glycoproteins.
AB  - This study evaluated infection and disease following caprine arthritis
      encephalitis lentivirus (CAEV) challenge of goats with existent immune response
      to CAEV surface and transmembrane envelope glycoproteins. Six Saanen goats were
      vaccinated three times with recombinant vaccinia virus rWR63 expressing
      glycoproteins encoded by the CAEV-63 envelope gene. Two goats were immunized with
      rWRSC11, a control vaccinia virus derived from the pSC11 vaccinia expression
      plasmid without the CAEV envelope gene. One pair of rWR63 vaccinated goats
      received a booster immunization with recombinant surface glycoprotein in Freund's
      complete adjuvant, a second pair was boosted by intravenous inoculation with
      rWR63, and the third pair was boosted by immunization with HPLC purified native
      CAEV surface glycoprotein in Freund's complete adjuvant. All six goats vaccinated
      with rWR63 developed antibody responses to CAEV envelope glycoproteins; however,
      CAEV-63 neutralizing antibody was not detected. Neither of the rWRSC11-vaccinated
      goats developed CAEV reactive antibody. All goats were challenged by intravenous
      inoculation with 10(6) TCID50 CAEV-63. All goats became infected following
      challenge infection, shown by detection of serum antibody to CAEV core proteins
      and virus isolation. Existent CAEV-63 immune responses did not detectably alter
      the severity of inflammatory joint lesions at 24 weeks postchallenge.

PMID- 7810059
TI  - Autologous red cell agglutination test for antibodies to feline immunodeficiency
      virus.
AB  - The T-lymphotropic lentivirus, feline immunodeficiency virus (FIV) is now
      recognised as a major viral pathogen affecting domestic cat populations
      worldwide. A rapid, autologous red cell agglutination test for antibodies to FIV
      has been developed. A synthetic peptide analog corresponding to the
      immunodominant epitope within the FIV transmembrane glycoprotein gp40 residues
      (680-715) KVEAMEKFLYTAFAMQELGC (Acm)NQNQFFK(BrAc)KIPLELWTR was conjugated to an
      anti-feline erythrocyte antibody using a thio-ether linkage. Within 3 min of
      adding this reagent to 20 microliters of whole blood, circulating antibody to the
      peptide epitope caused agglutination of the red blood cells. The performance of
      this simple test is comparable with the two commercially available enzyme
      immunoassay (EIA) kits and an EIA based on this peptide. A variant of the gp40
      (680-715) peptide corresponding to the FIV, PPR strain gp40 (678-716) sequence
      was also synthesised and no difference in reactivity was observed in an EIA on
      211 seropositive samples, indicating that the peptide-based test may be
      applicable to other known strains of the virus.

PMID- 7810060
TI  - Heterologous strain challenge of cattle immunized with Anaplasma marginale outer
      membranes.
AB  - In this study, we tested the hypothesis that outer membrane immunization would
      induce protection against an antigenically variant strain. Outer membranes were
      isolated from the Virginia strain of Anaplasma marginale using density gradient
      centrifugation, combined with saponin adjuvant, and used to immunize Friesian
      cattle in Zimbabwe. Immunized cattle developed high antibody titers (80,000
      160,000) against outer membrane polypeptides including MSP-2 and MSP-5 in both
      the homologous Virginia and heterologous Zimbabwe strains. Outer membrane
      immunized cattle were protected significantly following challenge with 10(4)
      Zimbabwe strain parasitized erythrocytes, demonstrated by significant differences
      in prepatent period and peak rickettsemia compared with adjuvant immunized
      control cattle. One outer membrane immunized animal was completely protected
      against infection. However, there were no overall significant differences in
      severity of anemia between cattle immunized with outer membrane and the control
      group, indicating that a significant reduction in rickettsemia does not
      necessarily result in less severe anemia.

PMID- 7810061
TI  - Quantitative assessment of the specific CD4+ T lymphocyte proliferative response
      in bovine herpesvirus 1 immune cattle.
AB  - We quantified the CD4+ T cell proliferation specific for bovine herpesvirus 1
      (BHV-1) in peripheral blood mononuclear cells from cattle. The stimulation index
      as detected in proliferative assays performed in the presence of BHV-1 antigen is
      highly variable in immune cattle. By using proliferative assays performed after
      negative selection we showed that, as expected, CD4+ T cells were the limiting
      cell type for antigen-induced proliferation. Neither B, gamma delta T nor CD8+
      cells seemed to be involved. The limiting dilution method was established to
      obtain quantitative estimations, namely frequencies of specific T cells. When
      limiting dilution cultures were supplemented with interleukin-2 (IL-2), an IL-2
      induced unspecific cell proliferation masked the specific T cell proliferation.
      Natural killer cells were not the major cell type involved, but CD4+ lymphocytes
      themselves seemed to respond to IL-2 irrespective of the presence of antigen.
      When cultures were performed without addition of IL-2, the frequency of BHV-1
      specific proliferative T cells could be obtained by the difference between the
      frequency of proliferating cells calculated in the presence and absence of
      antigen. The method provides a sensitive and quantitative means to measure the T
      cell immune response to BHV-1 vaccine candidates.

PMID- 7810062
TI  - Influence of experimentally induced endogenous production of cortisol on the
      immune capacity in swine.
AB  - Field studies have suggested that 'stressors', such as transportation and mixing,
      might interfere with the immune competence of pigs. Therefore, an experimental
      model was established to study the influence of elevated concentrations of
      circulating cortisol on the immune capacity in swine. Three experimental groups,
      with six pigs in each, were immunized twice, 4 weeks apart, with Mycoplasma
      hyopneumoniae antigen. Endogenous production of cortisol was induced by
      intramuscular injection of adrenocorticotropic hormone (ACTH) twice daily. One
      group received ACTH during the week before and after the second immunization, one
      group during the week after the second immunization only, while one group served
      as untreated controls. The treatment with ACTH induced high, but physiological,
      concentrations of cortisol in plasma. Simultaneously, the number of lymphocytes
      per milliliter blood decreased while the neutrophil number increased. The
      elevated concentrations of cortisol also coincided with reduced proliferation and
      interleukin-2 production by blood lymphocytes stimulated with the mitogens
      concanavalin A and phytohemagglutinin in vitro, while the responses to pokeweed
      mitogen were less affected. The suppression of mitogen responses was more
      pronounced in cultures of whole blood than in cultures of purified peripheral
      blood mononuclear cells (PBMC). Antibody production, induced by M. hyopneumoniae
      in cultures of purified PBMC was also inhibited by ACTH treatment. Both the rate
      of increase and the magnitude of the antibody production induced by the primary
      immunization were reduced. In contrast, no effects of ACTH treatment were
      recorded for the response to the second immunization or on the serum levels of
      antibodies to M. hyopneumoniae.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7810063
TI  - The production of anti-H-Y monoclonal antibodies: their potential use in a sex
      test for bovine embryos.
AB  - In an attempt to improve the accuracy of sexing bovine embryos, new anti-H-Y
      monoclonal antibodies were produced and selected, using an extended screening
      procedure. In addition to the commonly used screening of soluble H-Y antigen
      sources, such as testis supernatant and Daudi supernatant, the binding
      specificity to cell surface H-Y antigen was tested also. A radioimmunoassay (RIA)
      employing male and, as a control, female bovine lymphocytes, and enzyme-linked
      immunosorbent assays (ELISAs) on solubilized membrane fractions resulted in the
      selection of a number of clones producing monoclonal antibody (mAb) with male
      enhanced binding. Four of the anti-H-Y mAb were assessed for binding to Day 7 or
      8 bovine embryos. The accuracy of sexing bovine embryos ranged from 58% to 71%.
      Two of the four antibodies did not react with presumed soluble H-Y antigen
      containing sources in an ELISA. These results raise doubts about the suitability
      of the presumed soluble H-Y antigen sources, Daudi, TM4 and testis supernatant,
      to be used in screening tests for anti-H-Y antibodies.

PMID- 7810064
TI  - Relative immunocompetence of the newborn harbour seal, Phoca vitulina.
AB  - The immune system of many mammalian species is not fully developed at birth, with
      newborns obtaining temporary immunological protection from maternal antibodies.
      Little is known of the immune system of the harbour seal, and developmental
      aspects of its immune system have not been systematically studied. We collected
      blood and milk samples from nine free-ranging mother-pup pairs throughout the
      lactation period on Sable Island, Canada, in an effort to characterise
      developmental aspects of the immune system of this newborn pinniped. Pup
      lymphocytes responded stronger to the mitogens concanavalin A,
      phytohaemagglutinin, and pokeweed mitogen than the lymphocytes of their mothers.
      In contrast to newborn cats and dogs, newborn seal pups developed high specific
      antibody responses after immunisation with an inactivated rabies vaccine.
      Circulating levels of total IgG in newborn pups were low (3% of maternal levels),
      but increased rapidly after colostrum intake (to 65% of maternal levels after 15
      days). A similar pattern of increase in pup serum was observed for phocine
      distemper virus specific antibodies which had been detected in the serum and milk
      of mothers, suggesting that the transfer of colostral antibodies is an important
      feature of temporary protection for the pup. We speculate that the relative
      immunocompetence of the harbour seal at birth reflects an adaptation to its
      relatively short nursing period and limited maternal care.

PMID- 7810065
TI  - Compartmentalization of specific B-cells in sheep mucosae associated lymphoid
      organs.
AB  - Numerous studies have shown that Peyer's patches (PP) contribute to the seeding
      of other lymphoid organs in sheep. This was demonstrated by perfusing labeled
      lymphocytes in PP, and later investigating their presence in drainage lymph
      nodes, spleen, peripheral blood or bone marrow. These data showed that PP export
      considerable numbers of cells every day, but provided no information as to their
      specificity. In this work, we used the enzyme-linked immunosorbent assay (ELISA)
      spot method to investigate, in the peripheral blood, mesenteric and cervical
      lymph nodes and tonsils from ten sheep, the numbers of specific B-cells, directed
      to four common bacteria of the oro-pharyngeal area of mammals: Streptococcus
      pneumoniae, Streptococcus pyogenes, Haemophilus influenzae or Klebsiella
      pneumoniae. The data were obtained from five sets of monozygous sheep, one animal
      of each pair being previously fed ribosomal preparations of these bacteria. Both
      prior to and after oral challenge, specific B-cells could be found in all the
      tissues tested. They were mostly IgG-producing cells and preferentially located
      in oro-pharyngeal drainage lymph nodes and tonsils. Their numbers increased in
      these lymph nodes after stimulation, while they decreased in mesenteric lymph
      nodes. These observations are consistent with the current hypothesis suggesting
      intestinal sensitization, proliferation and fast emigration of specific B-cells
      after oral challenge.

PMID- 7810067
TI  - The effect of eicosanoids on rainbow trout, Oncorhynchus mykiss, leucocyte
      proliferation.
AB  - Proliferation of rainbow trout head kidney leucocytes in response to the mitogen
      phytohaemagglutinin-P (PHA-P) was modulated in the presence of inhibitors of
      eicosanoid synthesis and by exogenous eicosanoids. The presence of indomethacin,
      a cyclooxygenase inhibitor, resulted in a stimulatory effect, whereas the
      presence of nordihydroguiaretic acid, a lipoxygenase inhibitor, resulted in an
      inhibitory effect on mitogenicity. The addition of prostaglandins and lipoxins
      was also found to be inhibitory, whilst the addition of leukotrienes was
      stimulatory. Some class/series effects of the eicosanoids were also apparent.
      Prostaglandin E2 was a more potent inhibitor than prostaglandin E3, and
      proliferation was more sensitive to the effects of leukotriene B4 than to
      leukotriene B5. Whilst PHA-P was able to directly induce the release of
      prostaglandins from head kidney leucocytes, it did not induce the release of
      lipoxygenase products.

PMID- 7810066
TI  - Newcastle disease virus vaccines: differences between Line C and Line 15I
      chickens with respect to virus replication and IgA responses in the gut and
      Harderian gland.
AB  - The Ulster 2C and Hitchner B1 strains of Newcastle disease virus were inoculated
      into inbred White Leghorn birds of the Reaseheath-C and 15I lines by the
      oculonasal route. Both viruses replicated in the Harderian gland (HG) and induced
      virus-specific IgA in the tears and bile. Ulster 2C but not Hitchner B1
      replicated in the small intestine and induced virus-specific antibody forming
      cells (AFC) in the small intestine. Line 15I birds produced 120-fold more virus
      and 13-fold more IgA-AFC in the small intestine than Line C birds. Line C birds
      produced 20-fold more virus in the HG and at least three-fold higher titres of
      lacrimal IgA than Line 15I birds. The level of local virus replication in the HG
      or small intestine, which varied according to the line of bird, positively
      predicted the local antibody response in the same organ. When low doses of Ulster
      2C were inoculated into Line C birds virus replication was low and irregular in
      birds older than 18 days whereas low doses of Hitchner B1 replicated in all ages
      of bird.

PMID- 7810068
TI  - Immunorestorative effect of glucan immunomodulator on guinea pigs with
      experimental ascariosis.
AB  - The immunorestorative effect of glucan immunomodulator, combined with porcine
      immunoglobulin and zinc (GI) on T- and B-lymphocytes and peritoneal macrophage
      phagocytic ability was studied in guinea pigs with experimental ascariosis
      (Ascaris suum) after a cyclophosphamide (CY)-evoked immunosuppression. During the
      migration phase of A. suum infection GI exerted a significant restorative effect
      on the CY-reduced percentage occurrence of T- and B-cell populations in the
      mesenteric, mediastinal and hepatic lymph nodes and spleen of A. suum hosts. On
      the contrary, it did not influence the CY-suppressed phagocytic activity and
      index of phagocytic activity of the peritoneal macrophages. The protective effect
      of the GI evaluated by the reduction in the number of migrating ascarid larvae in
      the lungs of guinea pigs after immunosuppression with CY and administration of GI
      was 14.46% higher, compared with the suppressed and infected group without
      administration of GI.

PMID- 7810069
TI  - The steroid/nuclear receptors: from three-dimensional structure to complex
      function.

PMID- 7810071
TI  - Structure, function, and regulation of androgen-binding protein/sex hormone
      binding globulin.
AB  - Despite over 20 years of research, the functions of ABP and SHBG remain elusive.
      The major reason for this lack of knowledge has been the unavailability of
      natural mutants with clinical defects for study. There is strong evidence that
      these binding proteins do act to modulate the gene regulatory actions of nuclear
      sex steroid receptors by controlling the availability of androgens and estrogens.
      In plasma, SHBG controls the metabolic clearance rate of sex steroids. In
      addition there is strong evidence that they have a much broader function. The
      identification of plasma membrane receptors in target tissues and the finding of
      homologous domains in several developmental proteins support other functions.
      Moreover, other experiments suggest the proteins may actually be hormones or
      growth factors. These findings are not compatible with a model that has the
      proteins only regulating free steroid hormone levels. Obviously, much more
      experimentation will be necessary to reveal the functions of ABP and SHBG. The
      recent discoveries have offered several clues to their functions and open new
      routes for study. These experiments, coupled with newly developed techniques,
      such as gene knockout by homologous recombination, make one optimistic that the
      functions of these unique proteins will be deciphered in the near future.

PMID- 7810070
TI  - Genetic diseases of steroid metabolism.
AB  - All major classes of biologically active steroid hormones (progestins,
      mineralocorticoids, glucocorticoids, and sex steroids) are synthesized from
      cholesterol through 11 different bioconversions. With the exception of 5 alpha
      reductase, all the enzymes mediating these reactions fall into two classes,
      cytochromes P450 and short-chain dehydrogenases. Cytochromes P450 are heme
      containing membrane-bound proteins with molecular weights of approximately 50,000
      that utilize molecular oxygen and electrons from NADPH-dependent accessory
      proteins to hydroxylate substrates. Short-chain dehydrogenases have molecular
      weights of 30,000-40,000, have tyrosine and lysine residues at the active site,
      and remove a hydride from the substrate, transferring the electrons of the
      hydride to NAD+ or NADP+. In most cases, this reaction is reversible so that the
      dehydrogenase can also function as a reductase under appropriate conditions.
      Inherited disorders in enzymes required for steroid biosynthesis have varying
      effects. Defects that prevent cortisol from being synthesized are referred to
      collectively as congenital adrenal hyperplasia. Because the enzymes required for
      cortisol biosynthesis in the adrenal cortex are in many cases required for the
      synthesis of mineralocorticoids and/or sex steroids, these classes of steroids
      may also not be synthesized normally. Thus, cholesterol desmolase and 3 beta
      hydroxysteroid dehydrogenase deficiencies affect synthesis of all classes of
      steroids in both the adrenals and gonads. Steroid 21-hydroxylase deficiency, the
      most common cause (> 90% of cases) of congenital adrenal hyperplasia, can affect
      both mineralocorticoid and glucocorticoid synthesis, but androgen secretion is
      usually abnormally high due to shunting of accumulated precursors into this
      pathway. Excessive secretion of androgens and mineralocorticoids occurs in 11
      beta-hydroxylase deficiency (the second most frequent form of congenital adrenal
      hyperplasia). Mineralocorticoid excess is also seen in 17 alpha-hydroxylase
      deficiency, but in this disorder sex steroid synthesis is defective. All defects
      that affect estrogen synthesis (deficiencies of cholesterol desmolase, 3 beta
      hydroxysteroid dehydrogenase, 17 alpha-hydroxylase, aromatase, and 17 beta
      hydroxysteroid dehydrogenase) are very rare, suggesting that the inability to
      synthesize placental estrogens may adversely affect fetal survival. A number of
      enzymes are expressed at sites of steroid action and regulate the amount of
      active steroid available to steroid receptors. Steroid 5 alpha-reductase converts
      testosterone to the more active dihydrotestosterone. Deficiency of this activity
      leads to incomplete development of male genitalia; 17 beta-hydroxysteroid
      dehydrogenase deficiency has similar phenotypic effects.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 7810072
TI  - Molecular biology of vitamin D action.

PMID- 7810073
TI  - Nuclear retinoid receptors and their mechanism of action.

PMID- 7810074
TI  - Molecular mechanisms of androgen action.
AB  - Androgens directly regulate a vast number of physiological events. These direct
      androgen effects are mediated by a nuclear receptor that exhibits four major
      functions or activities: steroid binding, DNA binding, transactivation, and
      nuclear localization. The SBD consists of a hydrophobic pocket of amino acids
      that exhibits high-affinity, androgen-specific binding. Based on studies of
      mutant AR, it appears that a number of different amino acids contribute to the
      steroid binding characteristics of the AR. The DNA binding domain confers
      sequence-specific binding to structures called androgen-responsive elements. The
      specificity of steroid binding and DNA binding provides a crucial basis for
      androgen-specific regulation of target genes. The nuclear localization signal
      shares homology with known nuclear localization signals and, coupled with the
      presence of androgens, is responsible for localizing the AR to the nucleus. The
      transactivation functions reside mostly in the NH2 terminus but the responsible
      domains are as yet poorly defined. Though the different domains can act as
      independent moieties, one domain can clearly alter the behavior of another
      domain. For instance, the SBD appears to inhibit the transactivating functions
      until steroid is bound and the amino terminus prevents DNA binding activity until
      steroid is bound. The relative ease of introducing mutations with polymerase
      chain reaction technology will facilitate further delineation of critical amino
      acids and domains responsible for the various activities of the AR. The recent
      cloning and characterization of AR promoters revealed that the AR genes are
      driven by a TATA-less promoter characteristics of housekeeping genes. Analysis of
      transcription rates, mRNA levels, and protein levels indicates that androgens and
      pkA and pkC pathways modulate expression of AR mRNA and protein. This indicates
      that the same signal pathways that interact to regulate androgen target genes
      also regulate the levels of AR in the target tissues. Surprisingly few androgen
      regulated genes have been well characterized for the mechanisms by which androgen
      regulates the gene. The C(3), Slp, probasin, PSA, and hKLK2 genes have provided
      examples where androgens regulate transcription. Posttranscriptional regulation
      by androgens has been demonstrated for the SVP1, 2, 3, and 4 and AR genes. The
      mechanisms underlying posttranscriptional regulation are poorly defined but
      substantial progress has been made in defining the critical elements that mediate
      transcriptional effects of androgens. Transcriptional effects are mediated
      through binding of androgen-AR complexes to specific DNA sequences called AREs.
      Simple AREs such as those found in C(3) and kallikrein genes tend to be
      permissive in that GR and PR can also act through the same element.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7810075
TI  - Role of androgens in prostatic cancer.

PMID- 7810076
TI  - Function/activity of specific amino acids in glucocorticoid receptors.

PMID- 7810077
TI  - [Individualized supplemented low-protein diet in patients with chronic kidney
      failure].
AB  - The possibility of developing protein-energy malnutrition poses a serious risk
      associated with long-term administration of a restrictive low-protein diet. We
      conducted a randomized prospective study designed to evaluate 36 patients with
      chronic renal failure in initial malnutrition (BMI 22%, albumin 35 milligrams, WQ
      2.02). In 20 of these patients (Group I), low-protein diet was supplemented with
      ketoanalogs of essential amino acids along with a low-phosphate drink from casein
      free protein. The diet of another 16 patients (Group II) was supplemented with a
      mixture of essential and non-essential amino acids of egg white. Three-month
      follow-up revealed a statistically significant improvement in selected metabolic
      parameters (Surea, albumin, WQ, valine HDL-CH cholesterol, SP and SCa),
      particularly in Group I (p < 0.01). In group II, the improvement was either not
      marked (p < 0.05) or no improvement was seen. Results of the study indicate that
      patients found to suffer from initial malnutrition require early dietary
      supplementation including ketoanalogs of essential amino acids and a special
      protein providing an adequate amount of energy.

PMID- 7810078
TI  - [A metabolic and gastroenterologic intensive care unit].
AB  - The authors analyzed the work of the metabolic intensive care unit which due to
      the gastroenterological orientation of the clinic deals increasingly with
      treatment of patients with serious gastroenterological conditions. Since 1989 995
      patients were hospitalized and the ratio of gastroenterological patients
      increased from 15% in 1990 to 35% in 1993. The most serious course and prognosis
      is in patients with hepatic failure who accounted for 42% of the total number of
      gastroenterological patients. Another large group was formed by a total of 46
      patients with acute pancreatitis and 40 patients with severe forms of non
      specific inflammations of the gut. The metabolic intensive care unit possesses
      also two artificial kidneys. During the mentioned period a total of 2195
      haemodialyses were made, incl. 613 on account of acute renal failure, 53 on
      account of intoxications and the remainder in chronic renal failure. Forty
      haemoperfusions were made on account of intoxications. The remainder of the
      patients suffered as a rule from serious impairment of the milieu interieur. The
      authors' experience and data in the literature indicate that care of these
      patients concentrated in specialized departments with skilled staff and
      satisfactory technical equipment enhances their hope of survival and improvement
      of the condition. It is increasingly apparent that the development of specialized
      intensive care units of the non-coronary type is important.

PMID- 7810079
TI  - [Use of immunoreactive calcitonin and sonography in the diagnosis of medullary
      carcinoma of the thyroid gland].
AB  - In a group of 94 patients with a histologically verified medullary thyroid
      carcinoma were 59 patients with the sporadic form and 35 patients with the
      familial form. After radical surgery and subsequent actinotherapy in all patients
      the values of immunoreactive calcitonin were monitored along with the sonographic
      examination. In all with calcified thyroid residues confirmed on sonography, or
      when metastases were detected in the liver, elevated or high levels of
      immunoreactive calcitonin were found. The authors emphasize the importance of
      this examination for the early detection of relapses of medullary thyroid
      carcinoma.

PMID- 7810080
TI  - [Significance of determination of antibodies to TSH receptors (using TRAK) in the
      diagnosis and monitoring of therapy in endocrine orbital disease].
AB  - The elevated antibody level against receptors for TSH assessed by the commercial
      set TRAK (Henning Berlin) supports the diagnosis of endocrine orbitopathy (EO)
      which is important in more complicated cases with unilateral EO or EO in
      euthyroid or hypothyroid patients. During treatment of EO by elimination of the
      thyroid with radioiodine 131I (with or without previous thyroidectomy) a decline
      of originally high TRAK values to normal suggests successful elimination.
      Persistence of high TRAK values is associated with a poorer therapeutic effect of
      elimination and reasons for this should be sought. In four of 26 such patients
      the authors found radioiodine accumulation in the residual thyroid tissue, in 8
      patients they found a non-accumulating residue by means of sonography. In 14
      patients within two years after administration of the radioiodine elimination
      dose a residue of the thyroid gland was not found by scintigraphy nor by
      sonography. Improvement of the therapeutic effect occurred in one of these
      subjects with a drop of the TRAK value after the 30th month following
      elimination, in another female patient after a high diagnostic radioiodine dose.
      Improvement of the protrusion after radioiodine treatment with or without
      previous incomplete thyroidectomy and was recorded in 33 subjects where a drop of
      the originally high level of TRAK antibodies occurred was significantly greater
      than in subjects where the TRAK values did not decline.

PMID- 7810081
TI  - [Rheumatoid arthritis--a diffuse connective tissue disease].
AB  - The authors describe in a group of 100 patients, mostly with a severe form of
      rheumatoid arthritis, subjects with so-called "severe" extraarticular affections
      which can threaten the patients' lives or cause substantial deterioration of its
      quality, and those subjects where rheumatoid arthritis was the cause of death.
      These affections were associated--directly or indirectly--with the basic disease.
      From the absolute number of revealed affections the authors do not want to draw
      any conclusions as they are aware of various factors which could influence them.
      They assume, however, that the assembled data provide evidence that the American
      Rheumatological Association was right to include rheumatoid arthritis among
      diffuse connective tissue diseases and that it must be considered not only a
      disease of the locomotor apparatus but a potential disease of the organism as a
      whole.

PMID- 7810082
TI  - [The clinical picture of stenoses of the trunk of the left coronary artery].
AB  - In 1991-1993 the authors made at the Second Medical Clinic of the Faculty
      Hospital in Hradec Kralove 651 coronarographic examinations: in 460 patients they
      detected ischaemic heart disease, of the latter 44 (9.6%) suffered from stenosis
      of the trunk of the left coronary. During the premorbid period the authors
      evaluated the grade of stenocardia according to the Canadian cardiovascular
      classification and also the incidence, number of coronary attacks and reason for
      indicating coronarography. In 29 patients (66%) the authors made an ergometric
      examination--in 82.8% the finding was positive and in 17.2 negative. The loading
      test was unequivocally positive only in complete obstruction of the left
      coronary, in case of multiarterial affection almost in all cases. Coronarography
      revealed only in 4 patients (9%) isolated stenosis of the trunk of the left
      coronary, most frequently the finding was also on two other (36.4%) or 3 (34.1%)
      arteries. Complete occlusion of the trunk of the left coronary was recorded in
      6.8%. An ejection fraction of 50% or more was recorded in 75% of the patients.
      Surgical revascularization was performed in 35 patients. Twenty-nine patients are
      followed up after operation on a long-term basis (on average for 7.8 months), 23
      of the patients report improvement of their complaints (65.7%). The investigation
      provided evidence that stenosis of the trunk of the left coronary is a relatively
      frequent finding in the patient population with ischaemic heart disease and that
      it is most frequently associated with affection of two and three
      arteries.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7810083
TI  - [Treatment of acute myocardial infarct with magnesium].
AB  - The author examined 78 patients with acute myocardial infarction (IM). Forty-four
      patients were treated with magnesium (Mg) in continual 48 hours infusions,
      whereby during the first 24 hours the patients were given 50 mmol Mg, during the
      subsequent 24 hours 12 mmol Mg. Thirty-four patients with acute IM served as
      placebo group. The two groups did not differ statistically as regards the
      presence of risk factors (hypertension, hyperlipoproteinaemia, smoking), the
      incidence of diabetes (DM), age, sex the presence of Q and non Q IM. The two
      groups did not differ as regards the frequence of streptokinase administration.
      During the 21-day follow-up period (period in hospital) the authors recorded the
      following results: 1. In the Mg group the incidence of heart failure was by 22%
      lower. 2. In the Mg group the incidence of arrhythmias was by 28% lower. 3. In
      the Mg group the mortality rate in hospital was by 22% lower. In the discussion
      the author deals with the mechanism of the protective action of Mg in acute
      myocardial infarction and gives serum Mg concentration recorded during Mg
      administration.

PMID- 7810084
TI  - [Late and slow diagnosis of acute promyelocytic leukemias--the main cause of
      early death].
AB  - Acute hypergranular promyelocytic leukemia (AML M3) belongs to malignant diseases
      leading very rapidly to death. Immediate treatment based on early diagnosis may
      cure one third of patients. The typical finding in peripheral blood of patients
      is pancytopenia with or without atypical promyelocytes. In published studies only
      15-25% patients exhibit leukocyte counts above 10 x 10(9)/l. Five of our ten
      patients studied had leukocyte count above 10 x 10(9)/l. The difference might be
      in connection with late and slow diagnosis of AML M3. AML is not taken into
      consideration during medical examination even if the disease occurs in medical
      family. Thus we describe clinical signs of AML M3 that could be divided into
      three main groups: bleeding, infections and anemia. In patients with bleeding or
      anemia or with infections repeating within a short period or with an infection
      and concurrent signs of bleeding or anemia the complete blood cell count should
      be examined immediately. If blood cell count abnormalities are found the patient
      should be sent immediately to hematology unit for further examination and
      treatment. Early diagnosis enables to start "differentiation therapy" with all
      trans retinoic acid that could be administered as monotherapy only in patients
      with leukocytes below 5 x 10(9)/l. Early diagnosis of AML M3 might ameliorate the
      fate of patients, since four of our five patients referred to us with elevated
      leukocyte counts expired in the first five days.

PMID- 7810085
TI  - [Elevated levels of plasma von Willebrand factor: a new risk factor for
      atherosclerosis?].
AB  - The authors assessed the plasma level of von Willebrand's factor in a total of
      104 patients aged 32-60 years. Of these 10 patients are free from confirmed
      ischaemic heart disease with no history of acute myocardial infarction and 94
      patients after acute myocardial infarction. Samplings for von Willebrand's factor
      in patients after acute myocardial infarction were made at least two months after
      the infarction. The patients were subjected to: A) ergometric examination, b) to
      ergometric and coronarographic examination. The patients after acute myocardial
      infarction with minimal atherosclerotic changes or without atherosclerotic
      changes on the coronaries had a normal or slightly elevated plasma level of von
      Willebrand's factor. With the number of coronary arteries affected with
      atherosclerosis the plasma level of von Willebrand's factor increased. In
      patients after infarction with evidence of atherosclerotic changes on the
      coronary arteries without other risk factors the plasma level of von Willebrand's
      factor was also high. The results stimulate the hypothesis that high plasma
      levels of von Willebrand's factor could be a risk factor of atherosclerosis.

PMID- 7810086
TI  - [Transesophageal ventricular stimulation and ventricular tachycardia in the
      period before implantation of a cardioverter-defibrillator].
AB  - The administration of an implantable cardioverter-defibrillator (ICD) is the
      method of choice in life-threatening ventricular tachyarrhythmias. This effective
      non-pharmacological intervention was a great advance in the prevention of sudden
      cardiac death. As to ventricular tachycardias, relapsing ventricular tachycardias
      based on ischaemic alone need not influence ventricular tachycardia. The
      mechanism of ventricular tachycardia in ischaemic heart disease is reentry and
      therefore this arrhythmia can be terminated not only by a defibrillation
      discharge but also by antitachycardiac stimulation. Various types of
      antitachycardiac stimulation are part of modern types of ICD. Evidence of the
      effectiveness of antitachycardiac stimulation (electrophysiological examination)
      permits to use it also by the transoesophageal approach. This treatment can be
      very effective and we can thus overcome the period before the definite
      administration of an ICD, as indicated by the case described.

PMID- 7810087
TI  - [The pharmacology of biphosphonates and their use in hypercalcemia].
AB  - Bisphosphonates, derivatives of pyrophosphates are substances which block the
      function of osteoclasts and thus break down bone. They can be administered by the
      oral and i.v. route. Oral treatment is limited by poor absorption which e.g. in
      clodronate varies between 1 - 5%. The long half-life of bisphosphonates adsorbed
      on bone makes it possible to achieve the desired effect by administration once in
      1 - 3 months. Bisphosphonates are considered the most effective drugs for
      treatment of hypercalcaemia. Their effect is, however, manifested on the second
      or third day and thus in case of a serious acute condition caused by
      hypercalcaemia it is necessary to use yet other treatment commonly recommended in
      hypercalcaemia.

PMID- 7810089
TI  - [Prophylaxis of infectious endocarditis].
AB  - In spite of introducing antibacterial agents in prophylaxis of infective
      endocarditis (I.E.) more than 50 years ago, the optimal scheme for indication and
      application of the prophylaxis has not been solved. Evidences accumulate that
      prophylaxis (being developed to cover some medical procedures leading to
      bacteremia) can prevent only a small part (< 10%) of cases of I.E. The most
      effective protection from I.E. is the systematic care for gums and mucosae of the
      mouth cavity.

PMID- 7810088
TI  - [Long-term administration of biphosphonates in oncology patients with bone
      involvement].
AB  - The usefulness of bisphosphonates in the treatment of acute hypercalcaemia has
      been known for some time. The problem of long-term administration of
      bisphosphonates to patients whose skeleton is afflicted with a malignant tumour
      is still being discussed. The benefit of ethidronate has not been confirmed.
      Clodronate and pamidronate administered in i.v. infusions or in adequate amounts
      by the oral route leads to a reduced incidence of hypercalcaemic crises and the
      number of pathological fractures. Both mentioned preparations diminish the
      intensity of pain, increase physical fitness and improve the quality of life of
      oncological patients. However, they do not prolong the survival period of these
      patients.

PMID- 7810090
TI  - [The effect of diuretics on the magnitude of the effect of isosorbide dinitrate
      given as a single dose and after long-term administration. Ergometric study in
      patients with stable angina pectoris].
AB  - The authors assessed in 24 men with stable angina pectoris, using means of
      ergometry, the antiischaemic and antianginose effects of a combination of the
      nitrate Iso-Mack retard and the diuretic Moduretic. The effects were compared
      with the effects of Iso-Mack retard administered alone and with the effects of
      placebo. The examination was made after a single dose of the drugs and after
      three-week administration. The authors revealed that a single dose of the
      diuretic significantly enhanced the effects of nitrate. During long-term
      administration the diuretic did not prevent a significant diminution of the
      nitrate effects. Finally the authors discuss possible mechanisms of development
      of tolerance for nitrates and possibilities how to influence this tolerance by a
      diuretic.

PMID- 7810091
TI  - [Transesophageal atrial stimulation in routine clinical practice].
AB  - The authors examined 90 patients by the method of transoesophageal atrial
      stimulation with different indications. They consider transoesophageal atrial
      stimulation a suitable method for basic examination of an impaired functional
      status of the sinoatrial node and atrioventricular conductivity. It is suitable
      for assessment of predisposition to supraventricular disorders of the rhythm and
      for testing the effectiveness of treatment of impaired supraventricular rhythm.
      The authors use it also for a modified loading test in patients with coronary
      heart disease. They evaluate transoesophagel al atrial stimulation as a simple,
      safe, non-invasive method, practically without contraindications, which extends
      our diagnostic and therapeutic possibilities, is not demanding from the technical
      and economic aspect and can be used in any hospital.

PMID- 7810092
TI  - [Adenosine triphosphate and supraventricular tachycardia].
AB  - Intravenously administered adenosine triphosphate (ATP) converts some
      supraventricular tachycardias to a sinus rhythm. Temporary atrioventricular block
      can help with the differentiation of different forms of supraventricular
      tachycardia. METHOD: Twenty-one patients with different forms of supraventricular
      tachycardia were subjected to electrophysiological examination for diagnostic or
      therapeutic (ablation) purposes. During tachycardia (after 5 minutes duration)
      ATP Spofa was administered by the i.v. route within 3 s into the cubital vein-
      0.3 mg per 1 kg body weight. RESULTS: One patient had two forms of
      supraventricular tachycardia. In the first group with auricular fibrillation (AF,
      n = 10), with auricular flutter (AFL, n = 5) and with automatic auricular
      tachycardia (AAT, n = 1) tachycardia was not eliminated by intravenously
      administered ATP. In the second group the authors were always able to eliminate
      paroxysmal supraventricular tachycardia, AV nodal reciprocal (AVNRT, n = 4) and
      atrioventricular reciprocal tachycardia (AVRT, n = 2) by intravenously
      administered ATP. CONCLUSIONS: 1. The authors conclude that ATP exerts an
      antiarrhythmic effect by blocking the reentry circuit in the AV node, i.e. it
      converts reentry supraventricular tachycardias (AVNRT and AVRT) to a sinus rhythm
      after reciprocal atrial activity. 2. The effect on atria can be proarythmogenic.
      3. The authors did not confirm the effect on abnormal automaticity.

PMID- 7810093
TI  - [A system for monitoring hemodynamic data and treatment of arterial hypertension
      (Part I. Evaluation of long-term results of classical therapy)].
AB  - In 383 hypertonic patients treated for prolonged periods in the classical way
      (stopped-care-approach) for an average of 12.5 years, all with more than three
      drugs, the authors used during comprehensive evaluation thoracic electric
      bioimpedance. In group (0) are 15.9% normotensive subjects, while 84.1% (189 men
      and 133 women) are divided into groups (III and IV) with 15.4% where treatment
      failed, into group (II) with controversial therapeutic effect, 32.4%, and group
      (I) 36.3% where a certain therapeutic effect was achieved. With regard to the
      reduction of systemic pressure (groups 0 and I), the success of classical
      treatment could be expressed as 52.2%. Normotensive subjects (41 men and 20
      women) were evaluated according to age, pulse index and the index of vascular
      resistance. Only 40 (10.4%) are normotensive and normodynamic. There are 24
      (6.2%) normotensive subjects with a normal index of vascular resistance. In
      women, contrary to men, independent on the age bracket (under 30 years, 30-60,
      over 60 years) hyperdynamic conditions predominate 2.9 x. In treated patients
      with persisting hypertension in groups II to IV the ratio of hypodynamia is
      increasing. In men there is a relatively greater increase of systemic vascular
      resistance, however, even in group IV there is a reduced (supernormal) index of
      systemic vascular resistance. The hyperdynamic syndrome is not a privilege of the
      young. It can be found also in men and women over 60 years of age.

PMID- 7810094
TI  - [A system of monitoring hemodynamic data and treatment of arterial hypertension.
      (Part II: Evaluation of short-term results of directed therapy)].
AB  - Short-term results of aimed treatment (4-6 weeks) in 100 consecutive controls (65
      men and 35 women) comprise reduction of systemic hypertension in 80% (as compared
      with 52.5% in those treated by the classical approach). Normodynamic normotension
      was achieved in 35% (as compared with 10.5%). Aimed treatment uses available
      antihypertensive drugs of the main classes, based on clinical examination
      supplemented by analysis of haemodynamic parameters in the CDDP system.

PMID- 7810095
TI  - [Blind insertion of a peritoneal catheter in continuous peritoneal dialysis
      therapy].
AB  - Insertion of the peritoneal catheter is most important for peritoneal continual
      dialysis. Various techniques described in the literature do not indicate an
      unequivocal preference of methods and the blind method used by the authors makes
      it possible to perform the procedure safely by a team of experienced well trained
      nephrologists and specialists in internal medicine.

PMID- 7810096
TI  - [Cytologic picture of medullary carcinoma of the thyroid gland].
AB  - The authors present cytological and clinical features of six cases of medullary
      carcinoma of the thyroid. They are quoting a review of the literature about the
      cytological picture of medullary carcinoma of the thyroid and they draw attention
      to the advances of immunocytology.

PMID- 7810097
TI  - [Increased bone density in patients with multiple myeloma treated with
      clodronate].
AB  - The indication of bisphosphonates in hypercalcemia is fully accepted, the long
      term therapy with bisphosphonates is still controversial. The aim of our study
      was to evaluate the influence of clodronate on the bone density of myeloma
      patients. Twenty patients were included in the study. Clodronate is administered
      in the total dose of 3,000 mg, which is delivered in 4-6 hour infusions, 600
      mg/day, once in tree 3 months. The effect of clodronate on bone density is
      evaluated by CT-densitometry in a period of 6 months. At the beginning of May
      1994, 15 patients had completed at least two estimations of bone density. The
      amount of hydroxyapatite in these six months increased in 9 patients, in one of
      them there was no change and in 4 of them decreasing bone density was detected.
      The mean bone density before the administration of clodronate was -2.6 SD
      (standard deviation of European standard of bone density for age and sex). After
      6 months of therapy the bone density increased to -2.3 SD. The mean amount of
      hydroxyapatite in spongiosa was raised from the mean value 32.71 mg/ml before
      clodronate administration to 38.91 mg/ml after the 6 month treatment period. The
      mean increase in calciumhydroxyapatite in trabecular bone mass was 6.2 mg.
      Clodronate contributed to the amelioration of bone pain in the majority of
      patients, but this effect is difficult to evaluate because of other treatment
      modalities administered concomitantly. The tolerance of clodronate was good. No
      impairments of renal function or other adverse effects were observed. Only in 2
      patients the decrease in calcium concentration caused slight tetania. Therefore
      close monitoring of the calcium level is recommended and in the case of its
      decrease below the physiological level peroral substitution of calcium was
      started.

PMID- 7810098
TI  - [Hemostasis in patients with acute leukemia treated with high doses of cytosine
      arabinoside: the effect of chemotherapy and infectious complications on
      hemostasis].
AB  - Haemostatic parameters were studied in 12 adult patients with acute myeloid
      leukaemia and acute lymphoblastic leukaemia in complete remission using high-dose
      cytosine arabinoside regiments together with with other drugs. Increased tissue
      plasminogen activator (t-PA:Ag) antigen 4 hours after AraC application (p < 0.05)
      as well as increased levels of plasminogen activator inhibitor activity (PAI) (p
      < 0.05) and fibrinopeptide A (FPA) antigen (p < 0.05) were observed on day 2. All
      patients during bone marrow aplasia suffered from infectious complications (7
      from sepsis and 5 from fever of undetermined origin). During that period of
      infection the increased levels of FPA on day 21 (p < 0.05), PAI on days 15 and 21
      (p < 0.05) and fibrinogen on day 21 (p < 0.05) as well as decreased values of
      antithrombin III (p < 0.05) on day 21 and protein C on day 15 (p < 0.05) were
      measured. t-PA:Ag, plasminogen, alpha 2 antiplasmin and fibrin(ogen) degradation
      products were within normal throughout infectious complications. None of the
      patients experienced clinically manifest thrombotic complication. Though the
      results demonstrate that changes found were not clinically important (even if
      they were statistically significant), and that haemostasis was compensated as
      well as that thrombosis was not serious problem, authors recommend routine
      haemostasis monitoring in acute leukaemia patients, especially at diagnosis, in
      association with chemotherapy and during infectious complications.

PMID- 7810099
TI  - [Prognostic significance of ascites in patients with liver cirrhosis].
AB  - The author evaluates the prognostic importance of ascites in 100 patients with
      cirrhosis of the liver. The patients were followed up on a log-term basis in a
      hepatology clinic and the diagnosis was confirmed morphologically. Ascites
      developed at a time when marked objective and laboratory signs of chronic liver
      disease were present. Ascites was diagnosed by physical examination and verified
      by ultrasonography. It was treated by contemporary procedures. Survival of
      cirrhotic patients with ascites was unfavorable--50% survived one year, 38% two
      years, 17% three years, 15% four years and only 9% five years. Ascites is thus
      still a very adverse prognostic indicator for patients with cirrhosis.

PMID- 7810100
TI  - [Modern therapy of ascites in liver cirrhosis].
AB  - Ascites is a common sign of decompensated cirrhosis of the liver. In order to
      improve the patient's quality of life, it is essential to treat him
      systematically. The authors present an algorithm of therapeutic procedures. The
      basis is major rest, restricted water and sodium intake. First choice diuretics
      are aldosterone blockers. The basic diuretic is furosemide. The authors mention
      also the most important complications of treatment with diuretics. They evaluate
      contemporary views on paracentesis and therapy by return of ascites into the
      circulation. Ascites refractory to treatment is an indication for transplantation
      of the liver.

PMID- 7810102
TI  - [Contribution to the discussion on the future relations between cardiology and
      internal medicine].

PMID- 7810101
TI  - [The present, something from the past and the future of therapy of type II
      diabetes (NIDDM). II].
AB  - Insulin resistance which is the typical sign of NIDDM and the metabolic "X"
      syndrome is the basic problem of successful treatment of NIDDM. The author
      discusses therapeutic possibilities--biguanides, some new perspective
      pharmaceutical preparations and possibilities of combined treatment with PAD and
      insulin. Although it is not quite clear so far which treatment is the best,
      prevention of late diabetic complications, intensive NIDDM treatment must be
      focused on perfect control of the blood sugar level as well as on correction of
      associated metabolic abnormalities, as much as possible.

PMID- 7810103
TI  - [The work organization of the pharmaceutical department of a hospital for light
      casualties].
AB  - The problem of differential approach in organization of treatment of servicemen
      who can be returned to their ranks without being evacuated away from Army (Front)
      zone occupies an important place among the questions of reorganization of the
      existing medico-evacuation system. This complicated problem cannot be solved
      without application of effective medications and organization of opportune and
      adequate supplies with all types of medical equipment. The experience of tactico
      special exercises has shown that task could be solved successfully by
      pharmaceutical section of a hospital for minimally wounded. The organic structure
      of this section is the following: chief of the section, pharmacist, chemist,
      medical assistant and practical nurse-washer. Besides standard pharmaceutical
      facilities new equipment and devices based on up-to-date technologies were used
      during the exercises.

PMID- 7810104
TI  - [Trends in the development of the technologies of field pharmacy].
AB  - One of the actual trends of the researches in Medical Service of Russian Armed
      Forces is the improvement of medical supplies on the basis of the development and
      application of new pharmacy technologies. The development of such technologies of
      dual-purpose facilities for stationary and field needs is economically effective.
      The social and economic effect of these technologies also is of great
      significance due to the possibilities of training of pharmaceutical personnel in
      the conditions of peaceful time. The integral index of quality of the applied
      technologies is from 3 to 38 depending on the quantity of modules.

PMID- 7810105
TI  - [The computerization of the teaching of prophylactic disciplines in a military
      medicine department].

PMID- 7810106
TI  - [A treatment and diagnostic unit based on the separate medical battalion].

PMID- 7810107
TI  - [The diagnosis of a posterior myocardial infarct by integral
      electrocardiotopography].

PMID- 7810108
TI  - [The psychological aspect of the rehabilitation of myocardial infarct patients in
      the functional recovery period].
AB  - The article deals with the results of examination of 46 patients with myocardial
      infarction who were transferred to hospital from various medical establishments
      of Moscow to pass rehabilitation procedures. As for the method of treatment all
      the patient were divided into 2 groups. The first group was composed by 29
      patients who have received complex treatment with the elements of psychotherapy,
      the second (control) group (17 patients) have received treatment without
      psychotherapy. The improvement of health status was marked in both groups, but in
      the first group the improvement of psychosomatic status, the indices of external
      breathing function, blood, acid-based state, and tolerance for physical load were
      better than in the second one.

PMID- 7810109
TI  - [The possibilities for the pathogenetic therapy of ischemic heart disease under
      cardioselective loading].
AB  - The authors describe the method for the treatment of ischemic heart disease (IHD)
      with stenocardia at rest or tension which is refractory for basic therapy. This
      method consists of intravenous injection of phosphobion on the background of
      transesophageal electrocardiostimulation. Anti-ischemic and positive hemodynamic
      effects were marked during application of this method in 16 patients with IHD. On
      the contrary the traditional method based on administration of
      adesinotriphosphorous acid didn't give positive clinical results.

PMID- 7810110
TI  - [An anatomicophysiological evaluation of the percutaneous ligation of the femoral
      vessels as a method for temporary hemostasis in trauma of the lower extremities].

PMID- 7810111
TI  - [Dermatitis in the tropics].

PMID- 7810112
TI  - [The safety of the jet (needle-free) injection].
AB  - The analysis of literature doesn't give strong confirmation that jet injection
      could provoke the transmission of the infection. Nevertheless such infection is
      possible because of retrograde flow of vaccine preparation which just has mixed
      with tissue liquid of a previous patient or taking into account a continuous
      contact of an injector head with patient's skin during injection. The design of
      the injector head has a certain significance on this matter. These risk factors
      can be eliminated by strict observation of rules for handling these instruments.
      It's necessary to conduct additional experimental researches to prove or refute
      the safety of jet injections.

PMID- 7810113
TI  - [The organization of specialized medical care for the army in the field].
AB  - The experience of combat actions, and especially of the wars in century XX proves
      that specialized medical care occupies an important place in the system of
      medical and evacuation support. Some elements of the specialized medical care
      have been originated even during the wars of centuries XVIII-XIX, but they had
      appeared under the influence of current situation and by the initiative of non
      government organizations or single persons. Specialized medical care have
      obtained strict organizational forms, and was formatted as scientifically
      developed system only during the years of the Great Patriotic war 1941-1945. The
      basic trends in its development were: the appearance of different types of
      specialized medical care and formation of specialized medical establishments
      (sections) on the basis of Army or Front hospital facilities (AHF & FHF). There
      were certain differences in AHF and FHF specialized medical care. Specialization
      in AHF was realized by temporal attachment of specialized groups form of a
      separate company of medical re-enforcement; as for FHF, medical specialists were
      assigned to the staff of military hospitals.

PMID- 7810114
TI  - [The experience of open pleural biopsy in the differential diagnosis of
      pleurisy].

PMID- 7810115
TI  - [The evaluation of the psychological status of servicemen who participated in the
      cleanup of the accident at the Chernobyl Atomic Electric Power Station by using
      the dynamic situational game Test].

PMID- 7810116
TI  - [The healthy life style and the health of the military collective].
AB  - The article gives the notion of the healthy mode of living (HML) as far as
      individual and collective health is concerned. There is a hygienic concept of HML
      which includes three postulates: hygienic comregension of health: HML concept as
      a system of complex measures; HML comprehension as the final goal of hygienic
      education. The authors enclose the individual and military contingency health
      formulas. There are schemes which contain ecological measures and hygienic auto
      education.

PMID- 7810117
TI  - [The characteristics of the medical and physical examination of flight personnel
      with anomalies of the heart conduction system].
AB  - The article summarizes the results of examination of a considerable number of
      flight personnel of the Air Forces with cardiac conduction system abnormalities.
      The article contains peculiarities and algorithm of examination of such patients.
      New expert approaches are given concerning this kind of patients as well as
      methodic recommendations on their medical examination. The data which were
      obtained during this researches make it possible to improve the work of flight
      medical evaluation.

PMID- 7810118
TI  - [The experience of medical support for the crew of the first atomic submarine].

PMID- 7810119
TI  - [The contribution of A. P. Kolesov to the development of Soviet surgery (on the
      70th anniversary of his birth)].

PMID- 7810120
TI  - [A. P. Chekhov and military physicians].

PMID- 7810121
TI  - [The training of medical personnel in the USA for action under extreme
      situations].

PMID- 7810122
TI  - [A scientific and practical conference devoted to the current problems of
      military and emergency medicine].

PMID- 7810123
TI  - Emergence of hantaviral disease in the southwestern United States.
AB  - Hantaviruses are parasites of small mammals, predominantly peridomestic and
      commensal rodents. They have a worldwide distribution. Hantavirus-related illness
      occurs in rural areas where humans come into contact with rodents. In most cases
      human infection is manifested by one of a variety of acute illnesses involving
      hemorrhagic fever and renal disease. In May 1993, a cluster of patients with an
      acute pulmonary disease with high mortality was noted in the Four Corners region
      of the southwestern United States. Serologic and genetic studies indicated that
      the etiologic agent was a novel hantavirus. The uncertainty engendered by the
      emergence of a new disease with high mortality forced a rapid response by state
      and federal agencies and by the University of New Mexico Medical Center,
      Albuquerque, where most patients from this region were referred. Considerable
      progress has been made in identifying infected cases on clinical and laboratory
      grounds and in ensuring that appropriate supportive care is made available to
      patients as soon as they are suspected of having hantaviral infection. Cases of
      hantavirus pulmonary syndrome--both new and retrospectively diagnosed--are still
      being recognized throughout the western United States. Many important questions
      remain unanswered.

PMID- 7810124
TI  - Incidence of digoxin toxicity in outpatients.
AB  - The incidence of digoxin toxicity among patients in hospitals has declined in
      recent years. To evaluate whether a similar decline has occurred in ambulatory
      care, we reviewed randomly selected medical records for 183 outpatients receiving
      ongoing treatment with digoxin at 10 urban and rural Department of Veterans
      Affairs Medical Centers in the Rocky Mountain region. The prevalence of
      traditional risk factors for digoxin toxicity--elevated serum digoxin and serum
      creatinine levels, hypokalemia, and a new prescription of an interacting drug-was
      established from computerized laboratory and pharmacy records. Of the 183
      patients, 50 (27.3%) had one or more risk factors for digoxin toxicity: serum
      digoxin levels were elevated in 13.6% of patients in whom a level was obtained,
      with hypokalemia in 14.3%, elevated creatinine levels in 17.9%, and possible drug
      interactions in 5.5% of patients over a 1-year period. Nevertheless, digoxin
      toxicity occurred in only 2 persons (1.1% or 1.4 per 100 patient-years of
      treatment). We conclude that digoxin toxicity was rare in this group of
      outpatients, even in persons presumed to be at high risk because of metabolic
      abnormalities, increased digoxin concentrations, or the use of interacting drugs.
      The low rate of digoxin toxicity in outpatients parallels the decline in the
      incidence of toxicity observed in hospital-based studies.

PMID- 7810125
TI  - Injuries to occupants in cargo areas of pickup trucks.
AB  - Transporting passengers in the cargo area of pickup trucks is a public health
      safety issue in the United States. Our study compared crashes involving
      passengers in the cargo area with those involving passengers in the cab. We
      obtained data for all injury events of pickup occupants for 1990 from the
      California Highway Patrol. A total of 702 traffic reports coded as having
      passengers riding in pickup truck beds involved 1,685 passengers in the cargo
      area and 865 in the cab. Significantly more events involving passengers in the
      cargo area occurred in summer in rural areas and were noncollisions than did
      events with only cab passengers. Crashes with passengers in the cargo area
      resulted in death in 5% of passengers. Of the drivers, 81% were male and 22% were
      younger than 20 years. Among the 1,685 passengers in the cargo area, 65% were
      male, 36% were younger than 15 years, and 30% were ages 15 to 19 years.
      Passengers in the cargo area were more frequently ejected and more seriously
      injured than their counterparts in the cab. Legislation to restrict travel in
      truck beds and the design of restraints for this area are some measures that may
      reduce the risk of injury.

PMID- 7810126
TI  - Prenatal substance use in a Western urban community.
AB  - To assess the extent of prenatal substance use in a predominantly white
      population in an urban area of the western United States and to develop a risk
      profile for this population, a cross-sectional prevalence study was done.
      Prenatal clinics (10 public and 10 private) anonymously recorded demographic
      information about and collected aliquots of routinely obtained urine specimens
      from women during prenatal visits. Urine specimens were screened by enzyme
      immunoassay for amphetamines, marijuana, cocaine, opiates, and ethanol. Of the
      935 women screened, 92 (9.8%) had urine specimens positive for one or more of
      these substances. Urine screens were positive in 56 (10.0%) of 562 women
      attending private clinics and 36 (9.6%) of 373 women attending public clinics.
      Only 7 of the 935 women (0.7%) had screens positive for cocaine. Ethanol was the
      most frequently detected substance in the private clinic group (6.4%), whereas
      marijuana was most common among women attending public clinics (5.1%). Although
      substance use in this group of pregnant women occurs at a lower rate and a
      different pattern from those found in other more densely populated areas, the
      rate is high enough to be of concern to all prenatal care professionals, who
      should incorporate substance use history taking and selective urine drug
      screening into their routine prenatal practices.

PMID- 7810127
TI  - Colorectal cancer. A new look at an old problem.
AB  - This discussion was selected from the weekly staff conferences in the Department
      of Medicine, University of California, San Francisco. Taken from a transcription,
      it has been edited by Nathan M. Bass, MD, PhD, Associate Professor of Medicine,
      under the direction of Lloyd H. Smith Jr. MD, Professor of Medicine and Associate
      Dean in the School of Medicine.

PMID- 7810128
TI  - Strategies for home-assisted ventilation.
AB  - The Council on Scientific Affairs of the California Medical Association presents
      the following epitomes of progress in chest diseases. Each item, in the judgment
      of a panel of knowledgeable physicians, has recently become reasonably firmly
      established, both as to scientific fact and clinical importance. The items are
      presented in simple epitome, and an authoritative reference, both to the item
      itself and to the subject as a whole, is generally given for those who may be
      unfamiliar with a particular item. The purpose is to assist busy practitioners,
      students, researchers, and scholars to stay abreast of progress in medicine,
      whether in their own field of special interest or another. The epitomes included
      here were selected by the Advisory Panel to the Section on Chest Diseases of the
      California Medical Association, and the summaries were prepared under the
      direction of Dr Cosentino and the panel.

PMID- 7810129
TI  - High-resolution computed tomography.

PMID- 7810130
TI  - Preoperative staging of lung cancer.

PMID- 7810131
TI  - Primary pulmonary hypertension.

PMID- 7810132
TI  - Selective decontamination of the gastrointestinal tract to decrease the incidence
      of pneumonia and mortality.

PMID- 7810133
TI  - Tropical lung disease.

PMID- 7810134
TI  - Evaluating patients with chest pain.

PMID- 7810135
TI  - Porphyria cutanea tarda and hepatitis C virus infection in a patient with acute
      liver failure.

PMID- 7810137
TI  - We tried it once. Recollections of an early government health care program.

PMID- 7810136
TI  - Pulmonary tuberculosis, amenorrhea, and a pelvic mass.

PMID- 7810138
TI  - How to capture a revolution.

PMID- 7810139
TI  - The acquired immunodeficiency syndrome in older persons.

PMID- 7810140
TI  - A patient's choice?

PMID- 7810141
TI  - The beef about balance.

PMID- 7810143
TI  - The beef about balance.

PMID- 7810142
TI  - The beef about balance.

PMID- 7810144
TI  - [Austrian emergency medicine in an international comparison].
AB  - The emergency medical systems (EMS) in Europe are of a high quality partly due to
      the presence of an emergency doctor at the scene. In those countries without
      emergency doctors in the field, the emergency medical technicians (EMT) are
      allowed by law to carry out medical interventions due to their special education
      including more than 2000 hrs of first aid training (paramedics). The efficiency
      of the EMS is essentially improved by the presence of paramedics, especially in
      connection with the increasing frequency of cardiac arrests due to the high
      incidence of cardiovascular disorders. In the non-European states where the mean
      life expectancy is low (< or = 70 a) bystander training is rarely introduced. The
      EMS in Austria is of European standard in the structure of the rescue chain. Some
      links of this chain require correction and improvement: bystander training has
      not yet reached its optimal expanse; the profession of an EMT has to be urgently
      recognized by law; the gaping difference between EMS in urban areas and rural
      areas has to be eliminated; the limited capacity of emergency admittance to
      hospitals is a weak link in the chain of survival.

PMID- 7810146
TI  - [Propofol in emergency care--areas of application and initial experiences].
AB  - So far propofol has only been used in clinical settings for sedation and
      induction of anaesthesia. This study describes several indications in preclinical
      and emergency events. All users were anaesthetists, so that experience of
      administration and dosage was extremely helpful. Since the drug met the expected
      criteria it is now regularly used for the sedation of ventilated patients during
      transport. The most important indications for preclinical induction of anesthesia
      with propofol are patients with isolated head injury and patients with
      respiratory insufficiency due to status asthmaticus resistant to therapy. After
      repeated unsuccessful attempts at therapeutic intervention with benzodiazepines
      and other antiepileptics we were able to interrupt status epilepticus in 11
      patients by means of propofol, thereby preventing the patient from being
      intubated as a consequence of iatrogenic respiratory failure. However, emergency
      doctors must always be aware of the severe cardiocirculatory side effects of the
      drug, and must, hence, ensure that hypovolaemia or cardiac failure is excluded or
      corrected prior to propofol administration.

PMID- 7810145
TI  - [Emergency management of ruptured/dissecting aortic aneurysm--diagnosis and
      therapeutic strategies].
AB  - Between December 1991 and January 1994 fifteen patients with a ruptured abdominal
      aortic aneurysm and seven patients with a dissecting aortic aneurysm were treated
      in our emergency department. Dissection/rupture of an aortic aneurysm is still a
      dramatic event with poor outcome, whereby survival depends largely on early
      diagnosis. In most cases the diagnosis can be made with reasonable assurance by
      history taking and physical examination. The most frequent differential diagnoses
      are pulmonary embolism and myocardial infarction (thoracic aneurysms) and renal
      or biliary colic and lumbago (abdominal aneurysms). The largest delay in
      commencing therapy is caused by patients' hesitation to call the Emergency
      Medical Service. Chest X-ray, echocardiography and abdominal sonography are of
      high diagnostic value, computed tomography confirms the diagnosis in most cases.
      Our Emergency Department provides the facilities for rapid diagnosis and
      interdisciplinary preoperative management of dissecting/ruptured aortic
      aneurysms.

PMID- 7810147
TI  - Effect of low dose sedation with diazepam on ventilatory response at moderate
      altitude.
AB  - Benzodiazepines are in wide use in out of hospital emergency medicine in at sea
      level, as well as in alpine rescue services. Ventilatory depression is a common
      side effect of high dose intravenous benzodiazepines. The objective of our study
      was to evaluate the effect of low dose benzodiazepines on ventilation at moderate
      altitude. DESIGN: Randomized, double blind, placebo controlled crossover trial.
      Blood gas analysis of 8 healthy subjects was performed before and one hour after
      5 mg of oral diazepam or placebo at 171 m and at 3,000 m altitude. PaO2 and PaCO2
      before and after diazepam or placebo medication at 171 m did not change
      significantly. At 3,000 m altitude. PaO2 decreased and PaCO2 increased
      significantly one hour after 5 mg of oral diazepam (PaO2 64.7 +/- 3.4 vs. 60.0 +/
      1.5 mmHg, PaCO2 28.3 +/- 2.3 vs. 33.3 +/- 1.8 mmHg, p < 0.05). Placebo did not
      influence PaO2 and PaCO2. CONCLUSION: Low dose diazepam inhibits ventilatory
      adaptation to mild hypoxia at moderate altitude. Caution in benzodiazepine use in
      moderate altitude is therefore necessary.

PMID- 7810148
TI  - [Thrombolysis of acute myocardial infarct: modifying factors of "door-to-needle
      time"].
AB  - Effect of thrombolytic treatment in acute myocardial infarction depends on
      several factors, most importantly on time to treatment. The door-to-needle time,
      the interval between admission and thrombolytic therapy initiation, may be one
      important factor. In a retrospective study, we analysed 151 patients who were
      admitted to our emergency department with acute myocardial infarction and who
      received thrombolytic treatment. We analysed door-to-needle time with respect to
      the factors age, gender, clinical symptoms, presence of prehospital ECG, presence
      of prehospital complications, day of admission, hour of admission, duration of
      pain and infarct site. We observed that the door-to-needle time is significantly
      shorter in those cases with a prehospital ECG (p < 0.001) or no prehospital
      complications (p < 0.001) as well as inferior infarction (p < 0.02). There was a
      trend towards a shorter interval in cases with typical chest pain plus autonomic
      symptoms (p = 0.05). No statistical significance was seen in respect to age,
      gender, day and hour of admission, and duration of pain. Door-to-needle time with
      respect to thrombolytic treatment seems to depend on several factors in the
      preclinical field. Improvement of prehospital diagnosis and prevention of
      preclinical complications might result in faster thrombolytic treatment of the
      patient after arrival at the emergency department.

PMID- 7810150
TI  - [Concomitant perforated ulcer and acute myocardial infarct--a diagnostic
      challenge in emergency medicine].
AB  - Clinical differentiation between acute myocardial infarction and peptic ulcer
      perforation may sometimes be difficult. We report on a sixty-five year-old
      patient who presented at the Emergency Department with upper abdominal pain and
      local tenderness suggestive of acute perforation of a gastric ulcer. However, the
      initial electrocardiogram (ECG) showed acute inferior wall myocardial infarction.
      Although abdominal pain is a major symptom of acute inferior wall myocardial
      infarction the history of gastritis and abdominal findings on admission of our
      patient required further exploration. The first plain abdominal radiograph was
      inconspicuous, therefore we performed a gastroscopy, which showed a prepyloric
      gastric ulcer. The second plain abdominal radiograph revealed air in the
      peritoneal cavity as sign of perforation. Echocardiography, ECG and the increase
      of heart enzymes confirmed acute inferior wall infarction. After successful
      surgical treatment of the perforated ulcer the patient recovered and progressed
      satisfactorily at the intensive care unit. He was discharged after three weeks
      and remains in good health. This case shows that rapid diagnosis and good
      interdisciplinary therapeutic management prevented a fatal outcome of acute
      myocardial infarction and concomitant gastric ulcer perforation in an elderly
      patient.

PMID- 7810149
TI  - [Multiple organ failure syndrome in protracted tachycardia (based on 4 cases)].
AB  - The multiple organ dysfunction syndrome (MODS) is mainly caused by sepsis-
      community acquired or more frequently by nosocomial infections acquired on the
      intensive care unit. Further causes are intoxications, burns and multiple trauma.
      MODS worsens the prognosis of intensive care patients. We report on four cases of
      MODS developing outside hospital as a result of sustained tachycardia. Severity
      of MODS was apparently dependent on the duration of tachycardia and was rapidly
      reversible after termination of the tachycardia. Our observations show that
      sustained tachycardia may also cause MODS.

PMID- 7810151
TI  - [Fall/winter depression and its therapy].
AB  - Seasonal changes in human behavior have been recognized since ancient times.
      Starting in 1980 systematic research has been carried out by Rosenthal et al.
      (1984), who described and characterized a psychopathological and clinical
      syndrome which is linked to fall/winter and shows remission in spring/summer and
      which was termed seasonal affective disorder (SAD). The symptomatology includes
      depressed mood, decreased energy, hypersomnia, increased appetite and
      subsequently weight gain and frequently carbohydrate craving. The efficacy of
      light therapy with bright, fluorescent, full-spectrum light has been widely
      demonstrated for treatment of fall/winter SAD. In addition, treatment with
      selective serotonin reuptake inhibitors appears to be successful in this
      condition.

PMID- 7810152
TI  - [Huntington chorea: (CAG)n repeats on gene IT 15 in Austria].
AB  - In March 1993 the gene IT 15 was identified on chromosome 4p and it was
      demonstrated that it contained an unstable (CAG)n trinucleotide repeat that is
      elongated in patients with Huntington's chorea (HC). Persons with more than 37
      (CAG)n repeats tend to have a higher risk of developing the disease. Testing the
      (CAG)n repeats in Austrian HC patients with PCR techniques shows correspondence
      between the clinical diagnosis of HC and genotypes [more than 42 (CAG)n repeats].
      There was a weak correlation between the number of (CAG)n repeats and age of
      onset, however, this finding is without diagnostic value due to the scatter of
      the values.

PMID- 7810153
TI  - The effect of cisapride on delayed colonic transit time in patients with
      idiopathic Parkinson's disease.
AB  - Disorders of autonomic regulation are common in patients with Parkinson's disease
      (PD). Patients most frequently complain of dysphagia and therapy resistant
      constipation, as far as the gastrointestinal tract is concerned. These symptoms
      have to be attributed to a neuronal degeneration. In a pilot study we therefore
      investigated the effect of stimulation of the myenteric plexus by cisapride. 11
      women and 13 men were examined, the average age was 67.3 years, the Webster
      rating 17 points. In 2 out of 24 patients, colonic transit was prolonged up to
      the limit, both with and without therapy. The other 22 patients showed an
      acceleration in transit on response to cisapride. On average the colonic transit
      of 130 hours was reduced to 79 hours. This objective improvement was associated
      with a subjective improvement. Central side effects or a worsening of
      Parkinsonian symptoms were not found. We conclude that cisapride is effective in
      the treatment of constipation in idiopathic PD.

PMID- 7810154
TI  - [Drug fatalities from the forensic medicine viewpoint. 10 years experiences of
      the Vienna Institute of Forensic Medicine].
AB  - The problem of illicit drug abuse has of course not spared Austria. In fact,
      considering only the increase in the official figures on drug-related deaths over
      the past few years, this problem has dramatically worsened in Austria. Drug
      related deaths represent the most serious consequence of substance abuse, but
      according to the Pompidou Group classification such deaths are only one of eight
      indicators in assessing the extent of drug abuse in a community. We analyzed
      reports on all postmortems classified as drug-related deaths according to the
      official definition of the Austrian Federal Ministry of Internal Affairs
      undertaken at the Institute of Forensic Medicine in Vienna between 1984 and 1993.
      The annual number of drug-related deaths increased nearly ten-fold during the
      study period. In about a third of the cases accidental single substance
      overdosage (of mainly a morphine-containing drug) was the cause of death. In the
      majority of the corpses more than one drug, including alcohol, was detected.
      During the past 10 years there was an evident trend towards a multisubstance
      abuse pattern. Since the plateau reached in 1988, the incidence of HIV-1
      infection among decreased drug injectors has decreased.

PMID- 7810155
TI  - [Schizophrenia and partial complex seizures--case report in diagnosis and
      differential diagnosis of psychoses and epilepsy].
AB  - We report on a 57 year-old patient with schizophrenia. After a 30 years course of
      the disease, he developed previous unknown psychopathological symptoms, and
      therapeutic interventions (neuroleptic drugs and electroconvulsive therapy)
      failed. Neurological examination and EEG revealed the diagnosis of complex
      partial epileptic seizures. MRI showed bitemporal localized cerebral lesions.
      Discussion focusses on generalization of microseizures in deep brain structures,
      and "kindling effect" of electroconvulsive therapy in a patient with pre-existing
      cerebral lesions.

PMID- 7810157
TI  - The tragedy of gun violence.

PMID- 7810156
TI  - [Intraoperative irrigation of the subdural space after traumatic spinal cord
      lesions (based on 4 case examples)].
AB  - In experimental investigations on primates it has been shown that after a
      standardized transverse lesion of the spinal cord subdural perfusion with an
      artificial liquor solution (Elliot's B solution) of the region of the injury
      improved the eventual motoric function achieved. We tried to reproduce these
      experimental results in the management of four patients with acute spinal cord
      injury after trauma of the vertebral column. Due to the difficulty of an exact
      evaluation in this initial study an objective positive effect of perfusion with
      Ringer solution (at 37 degrees C) could not be confirmed in these patients.
      Nevertheless, the possibility of a positive influence of this adjuvant operative
      treatment on spinal cord injuries should be studied in a greater collective of
      patients. A multicentre study would be essential because of the limited number of
      cases in a single hospital.

PMID- 7810158
TI  - Guns and me.

PMID- 7810159
TI  - Firearm injuries among children and adolescents: I. The facts.
AB  - Although injuries, both intentional and unintentional, are the major cause of
      death of children under age 19, the rate of death from motor vehicle injuries has
      fallen during recent years, while the rate of injury death from violence is
      increasing. This increase in death rate is a reflection of greater availability
      of handguns in our society and greater numbers of handgun-related deaths. This
      article examines the facts related to firearm death and injury among America's
      youth. Physicians need to be armed with the facts to lead the forces to remove
      handguns from the environment of children.

PMID- 7810160
TI  - Firearm injuries among children and adolescents: II. The physician's role in
      prevention.
AB  - Firearm-related injury is a major public health problem in the United States.
      Many children are exposed to handguns in their own homes and in homes where they
      play and visit. By use of anticipatory guidance and preventive counseling in the
      office, physicians can educate their patients about the danger to the family
      (especially to children) of having a gun in the home. If patients keep a gun at
      home, they should be counseled to empty it and lock it up. Physicians also have
      the opportunity to be strong public advocates for establishing policies that lead
      to increased gun safety in the community.

PMID- 7810161
TI  - Trends in motor vehicle and firearm deaths in Wisconsin: an analysis for
      examining prevention strategies.
AB  - Motor vehicle crash (MVC) deaths in Wisconsin have steadily declined since the
      1970s. Multiple prevention strategies have been applied resulting in the lowest
      MVC death rate in 30 years. If current trends continue, firearms will exceed MVCs
      in Wisconsin by the year 2001. Multiple prevention strategies based on the public
      health model need to be applied to firearms.

PMID- 7810162
TI  - Firearm mortality trends in Wisconsin.

PMID- 7810163
TI  - The Wisconsin firearm injury surveillance system.

PMID- 7810164
TI  - SMS kicks off statewide CHILD SAFE health initiative to reduce firearm injuries,
      deaths among children, teens.

PMID- 7810165
TI  - Inhibition of rat hepatic aryl hydrocarbon hydroxylase activity by a series of 7
      hydroxy coumarins: QSAR studies.
AB  - 1. Molecular orbital calculations, by the Modified Intermediate Neglect of
      Differential Overlap (MINDO/3) method, of a series of twenty-five 8-acyl-7
      hydroxy coumarins show that the inhibition of aryl hydrocarbon hydroxylase (AHH)
      activities (cytochrome P4501, CYP1 activity, primarily CYP1A1) for 23 of these
      compounds is related to their structural parameters. The two remaining compounds
      are the only chlorinated derivatives; these are inactive towards the AHH system
      and were excluded from the quantitative structure-activity relationship (QSAR)
      analysis. 2. The results of multiple regression analyses show that AHH activity
      is dependent on the energy of the highest occupied molecular orbital, E(HOMO), in
      a single variable expression for the 23 compounds. However, a three-variable
      expression involving superdelocalizabilities provides a more significant
      correlation with biological activity. 3. The inactivity of the two chlorinated
      derivatives can be rationalized in terms of their low degree of molecular
      planarity, as estimated by the area/depth2 parameter, which presumably precludes
      them from interaction with CYP1.

PMID- 7810166
TI  - Identification of two new types of S-linked conjugates of Etoc in rat.
AB  - 1. Two major metabolites of 14C-labelled (4S,1R)-trans-Etoc[(S)-2-methyl-4-oxo-3
      (2-propynyl)cyclopent-2-enyl (1R)-trans-chrysanthemate] were purified using a
      combination of chromatographic techniques and identified by spectroanalysis
      (nmr(HMBC) and FAB-, TSP-MS). These were established as new types of S-linked
      conjugates (sulphonic acid and mercapturic acid types). 2. To examine the
      mechanism of formation of the sulphonic acid and mercapturic acid conjugates,
      sodium sulphate or glutathione labelled with 35S were administered to rat along
      with unlabelled trans-Etoc. Both sulphonic acid and mercapturic acid conjugates
      were found in the excreta, more of the former being yielded with 35S-sodium
      sulphate than with 35S-glutathione, implying that a sulphonic acid was
      incorporated into the double bond of a possible intermediate after reduction of
      sulphate to sulphite. The mercapturic acid conjugate was produced only with 35S
      glutathione, implying incorporation of glutathione into the triple bond before
      subsequent generation of mercapturic acid from the glutathione conjugate. 3.
      Additional investigation of whether or not the mercapturic acid conjugate was
      produced by mixing the alcohol moiety of Etoc, PGL (4-hydroxy-3-methyl-2-(2
      propynyl)cyclopent-2-en-1-one) and N-acetyl-L-cysteine under alkaline conditions.
      However, spectral data for the synthesized compound were not the same as those of
      the metabolite generated in vivo. That is, the addition reaction appeared to
      proceed by anti-Markownikov's rule, whereas the in vivo metabolite was apparently
      formed according to Markownikov's rule. Addition of glutathione at a triple bond
      has not been reported to our knowledge for any other foreign compounds in
      mammalian species.

PMID- 7810167
TI  - Sulphotransferase-dependent dehydration of atropine and scopolamine in guinea
      pig.
AB  - 1. Enzymatic dehydration of atropine and scopolamine was studied in guinea pig.
      2. The incubation of these alkaloids with guinea pig liver cytosol in the absence
      of cofactors gave no dehydrated metabolite. However, when atropine and
      scopolamine were incubated with cytosol supplemented with ATP and sodium
      sulphate, dehydrated metabolites, apoatropine and aposcopolamine were formed. The
      formation of these metabolites was confirmed by gas chromatography-mass
      spectrometry. 3. The reaction required ATP as well as cytosol as the obligatory
      factors. Deletion of sodium sulphate from the reaction mixture also resulted in a
      decrease of the activities, although this treatment showed limited effect when
      the low concentration of atropine was used. Furthermore, dehydroepiandrosterone,
      an excellent substrate for hydroxysteroid-sulphotransferase, effectively
      inhibited the in vitro activity of atropine dehydration. 4. Administration of
      dehydroepiandrosterone to guinea pig followed by atropine treatment caused
      decreased urinary excretion of apoatropine. 5. These results strongly suggested
      that the dehydration of atropine and scopolamine takes place via the sulphate
      conjugate intermediates produced from the sulphotransferase-catalysed reaction.
      The present finding is the first example of the sulphotransferase-dependent
      dehydration of a drug, and its generality in drug metabolism is discussed.

PMID- 7810168
TI  - Metabolism of finasteride in rat hepatic microsomes: age and sex differences and
      effects of P450 inducers.
AB  - 1. The age- and sex-related metabolism of finasteride and the effects of P450
      inducers and inhibitors were investigated using rat hepatic microsomes. 2. No
      marked age difference (3-13 weeks) in the rates of finasteride disappearance and
      the formation of 1 (omega-hydroxyfinasteride) and 4 (6 alpha-OH finasteride) was
      observed in the male rat. Whereas the rate of 1 formation remained about the same
      in male rat aged 1 year as compared with rat aged 7 weeks, a 21 and 45% decrease
      in the rate of finasteride disappearance and 4 formation, respectively, were
      observed. 3. The rates of finasteride disappearance and metabolite formation 1
      and 4 in the female rat decreased with an increase in age (3-7 weeks). Metabolite
      4 was hardly formed by the hepatic microsomes from the female rat at 7 weeks of
      age. 4. Hepatic microsomes from the male rat treated with phenobarbital (PB) and
      dexamethasone (Dex) increased the rate of the finasteride disappearance (PB, 5.5
      fold; Dex, 11.6-fold), whereas no increase in this activity was observed after
      administration of beta-naphthoflavone (BNF). Similarly, pretreatment of the
      female rat with PB and Dex resulted in increases of 26.6 and 8.4-fold in the rate
      of finasteride disappearance, respectively, whereas no inductive effect on this
      activity was observed in the BNF-treated female rat. 5. These observations
      suggest that finasteride is metabolized by P4502B, P4502C, and P4503A subfamilies
      in the male rat and by P4502B and P4502C subfamilies in the female rat.

PMID- 7810169
TI  - Changes in content of P450 isozymes in hepatic and renal microsomes of the male
      rat treated with cis-diamminedichloroplatinum.
AB  - 1. The changes in the activity of drug-metabolizing enzymes and in the content of
      P450 isozymes in renal and hepatic microsomes after treatment of the male Sprague
      Dawley rat with cis-diamminedichloroplatinum (Cisplatin, CDDP) were examined. 2.
      NADPH-P450 reductase activity in renal microsomes was significantly increased by
      treatment with CDDP, but lauric acid omega- and (omega-1)-hydroxylation
      activities of renal microsomes were not increased. 3. The level of P4502C23 was
      increased significantly and levels of P4504A2 and 4A8 tended to increase in renal
      microsomes. 4. In hepatic microsomes, lauric acid omega-hydroxylation activity
      was increased, but (omega-1)-hydroxylation activity was not. Levels of P4502C11
      and 3A2, which are male-specific forms, were decreased, whereas levels of
      P4502A1, 2C7 and 2E1 were increased in hepatic microsomes. The levels of P4504A2
      and 4A3 were increased by CDDP and the level of P4504A1 was not changed. Changes
      in the protein levels of P450 by CDDP were consistent with those in the mRNA
      levels reported previously (LeBlanc et al. 1992). 5. Male-specific forms in rat
      liver such as P4502C11 were decreased by CDDP, but those in the kidney such as
      P4504A2 was not. Therefore, CDDP has different influences on the regulation of
      hepatic and renal P450s.

PMID- 7810170
TI  - Metabolism of 1,1-dichloro-2,2,2-trifluoroethane in rats.
AB  - 1. Chlorofluorohydrocarbons are presently being developed as alternatives for
      ozone-depleting chlorofluorocarbons. 1,1-Dichloro-2,2,2-trifluoro-[2-14C]-ethane
      (HCFC-123) is a chlorofluorohydrocarbon with potential widespread use and
      associated human exposure. As a part of the toxicological evaluation of HCFC-123,
      its metabolism was studied in rodents in a closed recirculating exposure system.
      2. Two male rats were individually exposed for 6 h. Excretion of radioactivity
      was monitored for 48 h after the start of the exposure. Of the radioactivity
      introduced into the chamber, 14% was recovered in urine within the period of
      observation. Excretion of metabolites in the urine was very slow. 3.
      Trifluoroacetic acid was the major metabolite of HCFC-123 and N-trifluoroacetyl-2
      aminoethanol and N-acetyl-S-(2,2-dichloro-1,1-difluoroethyl)-L-cysteine were
      identified as minor urinary metabolites of HCFC-123. 4. Forty-eight hours after
      the start of the exposure, covalent binding of radioactive metabolites to protein
      was highest in liver followed by kidney and lung. Covalent binding above
      background levels was not observed in pancreas and testis, the target organs of
      HCFC-123 tumourigenicity. 5. These results suggest that the biotransformation of
      HCFC-123 in rodents follows a pathway identical to those of the extensively
      studied structural analogue halothane.

PMID- 7810172
TI  - Effect of AT-125 on the metabolism of propachlor and the glutathione conjugates
      of propachlor and bromobenzene in rat.
AB  - 1. Dosing rats with the gamma-glutamyl-transpeptidase inhibitor AT-125 results in
      the excretion of free glutathione in the urine of rat: this treatment did not
      lead to the excretion of glutathione conjugates of orally dosed xenobiotics,
      neither did AT-125 increase the biliary excretion of glutathione conjugates. 2.
      Dosing rat with AT-125 prior to dosing with 2-chloro-N-isopropylacetanilide
      decreased the excretion of 2-methylsulphonylacetanilide metabolites from 23% of
      the dose to < 0.5%. 3. We conclude that glutathione and glutathione-xenobiotic
      conjugates are probably not processed in vivo by the same pathway, and that AT
      125 can alter the in vivo transport of mercapturic acid pathway metabolites.

PMID- 7810171
TI  - Metabolism of coumarin and 7-ethoxycoumarin by rat, mouse, guinea pig, cynomolgus
      monkey and human precision-cut liver slices.
AB  - 1. The metabolism of 50 microM 7-ethoxycoumarin and 50 microM [3-14C]coumarin has
      been studied in precision-cut liver slices from the male Sprague-Dawley rat,
      female DBA/2 mouse, male Dunkin-Hartley guinea pig, male Cynomolgus monkey and
      man. 2. In liver slices from all five species 7-ethoxycoumarin was metabolized to
      7-hydroxycoumarin (7-HC), which was extensively conjugated with D-glucuronic acid
      and sulphate. In rat and mouse, 7-HC was preferentially conjugated with sulphate,
      whereas rates of glucuronidation and sulphation were similar in the other three
      species. 3. [3-14C]coumarin was metabolized by liver slices from all five species
      to various polar products and to metabolite(s) that bound covalently to liver
      slice proteins. In Cynomolgus monkey and both human subjects studied, 7-HC was
      the major metabolite that was conjugated with D-glucuronic acid and sulphate,
      whereas in rat the major metabolites were products of the 3-hydroxylation pathway
      and unknown metabolites. Major metabolites in mouse liver slices were 7-HC, 3
      hydroxylation pathway products and unknown metabolites, and in guinea pig liver
      slices, 7-HC and unknown metabolites. 4. The metabolism of 7-ethoxycoumarin to
      free and conjugated 7-HC and [3-14C]coumarin to total polar products was greater
      in liver slices from mouse and Cynomolgus monkey than the other three species. 5.
      With liver slices from all five species there appeared to be little difference in
      the extent of metabolism of 7-ethoxycoumarin and [3-14C]coumarin to various
      products in either a complex tissue culture medium (RPMI 1640 plus foetal calf
      serum) or a simple balanced salt solution (Earle's balanced salt solution). 6.
      These results demonstrate that precision-cut liver slices are a valuable in vitro
      model system for investigating species differences in xenobiotic metabolism.
      Generally, the observed species differences in coumarin metabolism in vitro agree
      well with available in vivo data.

PMID- 7810173
TI  - Oral bioavailability and disposition of sulphadimethoxine in lobster, Homarus
      americanus, following single and multiple dosing regimens.
AB  - 1. Single and multiple oral doses of sulphadimethoxine or sodium
      sulphadimethoxine were administered by gavage to lobster, and sequential samples
      of haemolymph were taken for analysis of parent sulphadimethoxine. Single doses
      of sodium sulphadimethoxine were given over a dose range of 14-70 mg/kg. Five 42
      mg/kg doses of sulphadimethoxine on alternate days were administered for the
      multiple-dose studies. Some experiments were conducted with radiolabelled (35S or
      14C) sulphadimethoxine, and the tissue distribution of radioactivity was
      determined at different killing times. 2. Pharmacokinetic parameters were
      obtained by fitting sulphadimethoxine concentrations in haemolymph to a one
      compartment model. Oral bioavailability at the 42-mg/kg dose, calculated from the
      area under the haemolymph concentration-time curve (AUC) relative to the AUC from
      intravascular administration, was between 47 and 52% for single or multiple doses
      of the free drug. The bioavailability of sodium sulphadimethoxine was dose
      dependent, at 97% for the 14 mg/kg dose, and 25% for the 70-mg/kg dose. The low
      bioavailability at the high dose probably resulted from poor absorption due to
      the limited solubility of sulphadimethoxine at the low pH of the lobster
      gastrointestinal tract. 3. Sulphadimethoxine and several polar metabolites were
      excreted in lobster urine. Polar metabolites were also found in the
      hepatopancreas and haemolymph. At least 20% of the 42-mg/kg dose was metabolized.
      The major vertebrate metabolite of sulphadimethoxine, N-acetylsulphadimethoxine,
      was a very minor metabolite in lobster. The identities of the polar metabolites
      were not established. 4. Elimination of sulphadimethoxine residues from muscle to
      < 0.1 microgram sulphadimethoxine equivalent/g tissue required 40 days after a
      single dose, or 44 days after the last of multiple doses. Concentrations of
      sulphadimethoxine residues in all other tissues were always greater than muscle
      concentrations. Data showed that sulphadimethoxine residues were very persistent
      in lobster tissues.

PMID- 7810174
TI  - Disposition of lupanine and 13-hydroxylupanine in man.
AB  - 1. The in vivo disposition of lupanine and 13-hydroxylupanine was studied in
      subjects identified as poor metabolizers (PM, n = 4) and extensive metabolizers
      (EM, n = 7) phenotypes for cytochrome P4502D6 (CYP2D6). 2. After oral
      administration (40.26 mumol), the half-life (t1/2) of lupanine determined from
      urinary excretion rate studies in EM subjects was 6.2 +/- 0.5 h (mean +/- SEM)
      with 95.5 +/- 6.0% of the dose recovered unchanged within 72 h. Similarly, in PM
      subjects t1/2 = 6.5 +/- 0.9 h and recovery 89.9 +/- 4.5%. 3. For orally
      administered 13-hydroxylupanine (37.83 mumol) the t1/2 in EM subjects was 6.8 +/-
      1.0 h with a recovery of 100.5 +/- 5.3%, and in PM subjects t1/2 = 5.9 +/- 1.6 h
      with a recovery of 102.5 +/- 4.8%. 4. The t1/2s of both lupanine and 13
      hydroxylupanine respectively did not differ significantly between EM and PM
      phenotypes. In addition, total recovery of dose for both alkaloids was similar
      between phenotypes. 5. In most subjects, > 76% of lupanine and > 85% of 13
      hydroxylupanine was recovered as the unchanged compound. Significant apparent
      partial dehydroxylation of 13-hydroxy-lupanine was observed in one EM (14% of
      dose) and one PM (34% of dose) subject. 6. Overall, the finding of a high urinary
      recovery of unchanged lupanine or 13-hydroxylupanine together with similar t1/2s
      for both alkaloids in EM and PM CYP2D6 phenotypes suggests that clinical toxicity
      is unlikely to result from the use of lupin seed in footstuffs.

PMID- 7810175
TI  - Coordinate induction of hepatic fatty acyl-CoA oxidase and P4504A1 in rat after
      activation of the peroxisome proliferator-activated receptor (PPAR) by sulphur
      substituted fatty acid analogues.
AB  - 1. In the liver of rat fed a single dose of 3-thia fatty acids, 3
      dithiahexadecanedioic acid (3-thiadicarboxylic acid) and tetradecylthioacetic
      acid, steady-state levels of P4504A1 and fatty acyl-CoA oxidase mRNAs increased
      in parallel. The increases were significant 8 h after administration, reaching a
      maximum after 12 h and decreased from 12 to 24 h after administration. 2. The
      corresponding enzyme activities of P4504A1 and fatty acyl-CoA oxidase were also
      induced in a parallel manner by the 3-thia fatty acids. The enzyme activities
      were significantly increased 12 h after administration and increased further
      after 24 h. This may reflect a possible effect of the 3-thia fatty acids not only
      on mRNA levels, but also on the translation and degradation rate of the two
      enzymes. 3. Repeated administration of 3-thia fatty acids resulted in an increase
      of the specific P4504A1 protein accompanied with an increased lauric acid
      hydroxylase activity. The correlation between induction of P4504A1 and fatty acyl
      CoA oxidase mRNAs and their enzyme activities may reflect a coordinated rather
      than a causative induction mechanism, and that these genes respond to a common
      signal. This suggests that the increased P450 activity may not be responsible or
      be a prerequisite for fatty acyl-CoA oxidase induction. 4. Since the peroxisome
      proliferator-activated receptor (PPAR) plays a role in mediating the induction of
      fatty acyl-CoA oxidase, we analysed the activation of PPAR by fatty acids and
      sulphur-substituted analogues utilizing a chimera between the N-terminal and DNA
      binding domain of the glucocorticoid receptor and the putative ligand-binding
      domain of PPAR. Arachidonic acid activated this chimeric receptor in Chinese
      hamster ovary cells. Inhibitors of P450 did not affect the activation of PPAR by
      arachidonic acid. Furthermore, dicarboxylic acids including 1,12-dodecanedioic
      acid or 1,16-hexadecanedioic acid only weakly activated the chimera. 3
      Thidicarboxylic acid, however, was a much more effective activator than the non
      sulphur-substituted analogues. In conclusion, the data suggest that the most
      likely mechanism of the induction process is fatty acid-induced activation of
      PPAR, which then leads to a coordinated induction of P4504A1 and fatty acyl-CoA
      oxidase.

PMID- 7810176
TI  - [The effect of tryptophan on the regulation of food intake in normal and
      overweight persons].
AB  - The neurotransmitter serotonin significantly contributes to the regulation of
      food intake and appetite behaviour. The cerebral serotonin synthesis depends on
      the availability of the precursor tryptophan. To examine how diets with different
      carbohydrate, protein and tryptophan content affect food preferences and the
      mood, healthy obese and non-obese male adults consumed the following isocaloric
      diets at breakfast: standard diet (60% carbohydrate), protein-rich diet (35%
      carbohydrate, 40% protein), carbohydrate-rich diet (80% carbohydrate), tryptophan
      supplemented diet (standard diet + 1.5 g tryptophan). The plasma concentration of
      tryptophan (TRP) and large neutral amino acids (LNAA) is determined by their
      uptake with the diet. In obese and non-obese adults the TRP/LNAA-quotient rose
      significantly by upto 0.40 to 0.57, following the tryptophan supplemented
      breakfast. The protein-rich diet reduced the TRP/LNAA-quotient. The preference of
      protein-rich food after the consumption of carbohydrate-rich diets (60-80%
      carbohydrate) was diagnosable with the non-obese person and not with the obese
      person. No obvious connection was detected between nutrient preferences and
      plasma TRP/LNAA-quotient. There was no influence of the plasma TRP/LNAA-quotient
      after meals with different nutrient relation on mood. Therefore it is concluded
      that different carbohydrate and protein content and also additional tryptophan
      supplementation of single meals is not able to modify the brain serotonin
      synthesis and release in healthy people in a kind that serotonin induced
      behaviour would be changed, at least on a short time basis.

PMID- 7810177
TI  - Dose dependency of fermentation and the extent of renal excretion of palatinit
      (isomalt) in rats with respect to its energy value.
AB  - The impact of dose-dependent caloric salvage by microbial fermentation processes
      in the lower gut and the extent of renal excretion for the overall energetic
      availability of the alternative bulk sweetener Palatinit were investigated in
      rats. To evaluate the extent of dose-dependent fermentation a conventional and a
      germ-free rat model were used and fecal excretions of Palatinit after
      intragastric application were compared. Because of the lack of bacterial
      colonization in the gastrointestinal tract in germ-free rat the difference in
      fecal excretion of Palatinit between germ-free and conventional rat is mainly due
      to bacterial fermentation. To determine the amount of renal excretion of
      Palatinit the urine was collected. The experiments were conducted using different
      amounts of Palatinit (300 and 1,200 mg/kg body weight = mg/kg b.w.). Fecal
      excretions of Palatinit and its monomers (sorbitol and mannitol) were measured by
      high-performance liquid chromatography (HPLC) and for the determination of renal
      excretions a gas chromatography system was used. After the application of 300
      mg/kg b.w. Palatinit only the breakdown product sorbitol could be recovered in
      the feces of germ-free rats (29% of the applied dose). No intact Palatinit could
      be found. In contrast, neither Palatinit nor the breakdown products sorbitol or
      mannitol could be detected in the feces of conventional rats after application of
      the same dose. After the application of the higher dose only small amounts of
      intact Palatinit were found in the feces of germ-free rats (average 12%). There
      was no intact measurable Palatinit in the feces of conventional rats. The fecal
      excretions of sorbitol and mannitol in the feces of the germ-free rats were 55%
      and 39%; in conventional rats only 21% sorbitol was excreted. Only traces of
      Palatinit, sorbitol or mannitol were found in the urine of conventional and germ
      free rats after application of the low as well as the high dose. In conclusion,
      this study clearly shows the dose dependency of fermentation and therefore the
      dose dependency of the energetic (i.e., caloric) availability of this
      disaccharide sugar alcohol. In the calculation of the energy value of Palatinit
      the renal excretion of Palatinit and its monomers can be neglected.

PMID- 7810178
TI  - Effect of dietary hyperlipidemic components and fish oil on concentration of
      lipids in liver and liver fatty acid profile of rats.
AB  - This investigation was attempted to clarify the effects of dietary hyperlipidemic
      components and fish oil on concentration of lipids in liver and liver fatty acid
      profile of rats. In a first experiment male Sprague-Dawley rats were maintained
      on a semipurified low-fat diet with 6.5% coconut oil and 1.5% safflower oil, but
      without added cholesterol, or a high-fat hyperlipidemic diet supplemented with
      7.3% coconut oil, 7.3% beef tallow, 0.4% safflower oil, and 1.5% cholesterol for
      28 days. Rats fed the hyperlipidemic diet were then switched to fish oil diets
      with 1.4%, 2.8%, and 5.6% fish oil in exchange for coconut oil and beef tallow
      for, respectively, 10 and 20 days. In a second experiment male Sprague-Dawley
      rats were fed low-fat or high-fat diets without or with 1.5% added cholesterol
      for 28 days. Half of each group was then changed to a fish oil diet (for 20 days)
      which contained 5.6% fish oil in exchange for coconut oil and beef tallow. In
      experiment 1, rats fed the hyperlipidemic diet had enlarged fatty livers within
      28 days. Experiment 2 showed that cholesterol in the diet was responsible for the
      accumulating liver lipids. Feeding diets with added cholesterol, the proportions
      of saturated fatty acids (SFA), especially 18:0, were markedly reduced in liver,
      whereas levels of monounsaturated fatty acids (MUFA) were greatly increased
      compared to diets without added cholesterol. This increase was most pronounced
      with respect to 16:1 and 18:1. In contrast, fish oil diets lowered MUFA level in
      liver in spite of its high MUFA content. Rats fed the highly saturated
      hyperlipidemic diet low in 18:2 n-6 had reduced 18:2 n-6 levels in liver compared
      to rats fed the low-fat diet without added cholesterol. Also, 20:4 n-6 level in
      liver was markedly reduced after the administration of the hyperlipidemic diet or
      the fish oil diets. Results of experiment 2 elucidate that cholesterol as well as
      fish oil sharply lowered 20:4 n-6 level in liver, which might be due to a reduced
      desaturation. In both experiments feeding fish oil increased all long-chain n-3
      polyunsaturated fatty acids (PUFA) in liver. This occurred in a dose-dependent
      fashion and reached a maximum level with 5.6% fish oil in the diet. When
      additional cholesterol was applied 22:6 n-3 level in liver fell. This indicates
      also an impaired desaturation of PUFA due to dietary cholesterol.

PMID- 7810179
TI  - [Effects of doses of cereal foods and zinc on different blood parameters in
      performing athletes].
AB  - A total of 51 athletes, randomly divided into two groups (with or without zinc
      supplementation) and respective two subgroups (with or without cereal diet) had
      been tested for their serum levels in respect of zinc, iron, copper, phosphorus
      and potassium over a period of 8 weeks, i.e. during a period of competition.
      Furthermore, subpopulations of lymphocytes were defined. Modifications of the
      immunologic defense mechanism with special regard to the zinc level could,
      however, not be detected. Minerals, i.e. zinc and iron revealed to decrease
      significantly during simultaneous uptake of certain amounts of the cereal
      products. This is due to the relatively high amounts of phytates in cereals which
      are capable to bind the trace elements in form of complex salts.

PMID- 7810181
TI  - [Evaluation of nutrient intake using fuzzy sets].
AB  - Fuzzy sets are especially suitable to evaluate the intake of a nutrient. For the
      evaluation of several components, the harmonic mean of the individual fuzzy
      values proves to be the best compromise. The mean of all nutrients results in the
      so called Prerow value, which can be used for the evaluation of the nutrition
      status. Maximizing the Prerow value is suitable for optimizing nutrition.

PMID- 7810180
TI  - Nutrient intake of endurance runners with ovo-lacto-vegetarian diet and regular
      western diet.
AB  - During an endurance run (1,000 km in 20 days) it was investigated whether an ovo
      lacto-vegetarian diet (OLVD) could cover the nutritional requirements of
      endurance athletes. A regular western diet (RWD) was used as reference. Both
      diets were offered with an energy content of 4,500 kcal per day and an energy
      percentage of carbohydrate:fat:protein of 60:30:10. The runners were divided into
      two dietary groups according to their usual dietary habits. The results of the 55
      participants who completed the race show that runners from both groups had the
      same intake of energy, carbohydrate, fat and protein. Runners of the OLVD group
      consumed more dietary fiber and polyunsaturated fatty acids as well as less
      cholesterol. With the exception of sodium chloride and cobalamin, the intake of
      the calculated minerals and vitamins was higher in the OLVD and exceeded the
      official recommendations. This study shows that an OLVD with a high nutrient
      density is adequate to cover the nutritional requirements of endurance-athletes.
      The intake and absorption of iron should be monitored closely in all diet groups.

PMID- 7810182
TI  - [Comparative studies of the bacterial and mycological status of ecologically and
      conventionally grown crops].
AB  - Wheat and rye derived from conventional and from alternative or ecological
      production was examined for bacterial and fungal contamination. The overall
      bacterial and fungal contamination was lower than 10(7.7) germs/g. The amount and
      type of germs in the grain corresponded to typical contamination of fresh crop.
      No difference in germ contamination of both conventionally and alternatively
      grown wheat and rye could be found. No correlation between bacterial or fungal
      contamination and thousand-kernel-weight was detected.

PMID- 7810183
TI  - [Progression of coronary sclerosis after smoking cessation].
AB  - Cigarette smoking is an established risk factor for the development of coronary
      artery disease, but whether cessation of heavy smoking influences progression of
      coronary artery disease is unclear. In 390 patients (359 men, 31 women; 52.4 +/-
      6.7 SD years) with coronary artery disease, two coronary angiograms were
      performed at an interval of 62.4 +/- 23.5 months. Smoking habits were obtained by
      questionnaires. Progression of coronary artery disease was defined as the sum of
      new stenoses, progression of existing stenoses and new coronary occlusions.
      Multivariate classification analyses of risk factor profile revealed cigarette
      smoking (amount per day and length of time) as the most relevant factor for
      progression of coronary artery disease. Non-smokers had a progression score of
      0.96 (95% confidence interval: 0.63-1.28) over the observation period. Former
      smokers (20.2 +/- 11.8 cigarettes/day for 19.4 +/- 7.6 years) who quit about 10
      years before the first angiogram showed a progression of 2.20 (95% confidence
      interval: 1.77-2.63; p < 0.01) compared to non-smokers. Those smokers (23.8 +/-
      9.2 cigarettes/day for 31.3 +/- 7.0 years) who quit at the time of the first
      angiogram showed a progression of 2.47 (95% confidence interval: 1.97-2.97; p <
      0.001). Current smokers (20.5 +/- 9.7 cigarettes/day for 34.8 +/- 8.5 years) had
      a progression of 3.17 (95% confidence interval: 2.35-3.99; p < 0.001). The data
      indicate that former heavy cigarette smoking continues to act as a significant
      risk factor for progression of coronary artery disease even after cessation. This
      does not mean that current cigarette smokers should not stop.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7810184
TI  - [Digoxin-induced constriction of epicardial coronary vessels in patients with
      coronary heart disease: reversibility by nitrates].
AB  - Heart diseases requiring glycoside therapy are often associated with coronary
      artery disease. This study evaluated quantitatively the effect of an intravenous
      bolus injection of digoxin (0.8 mg) on diameters of epicardial coronary arteries
      in 11 patients with coronary artery disease. Coronary angiograms were taken up to
      30 min following intravenous administration of glycosides. The maximum decrease
      in mean diameters of angiographically normal coronary segments was 10.0 +/- 3.5%
      (p < or = 0.001) compared to control. Maximum reduction in minimal diameters of
      stenotic segments was 22.1 +/- 13.1% (p < or = 0.001). This vasoconstriction
      could be reversed with nitroglycerin. Thus, intravenous administration of digoxin
      induces vasoconstriction of normal and stenotic coronary arteries, which could
      cause ischemic complications in the presence of high-grade stenoses. Since
      digoxin-induced vasoconstriction could be reversed with nitroglycerin,
      concomitant vasodilator therapy is recommended.

PMID- 7810185
TI  - [The form of atherosclerotic coronary plaques: pathoanatomic concepts and new
      insights using intravascular ultrasound].
AB  - In addition to the degree of vessel obstruction and to the composition of the
      atheroma, the geometric shape of the plaque--in particular the presence of non
      diseased wall segments--is an important factor in the pathophysiology and therapy
      of coronary heart disease. The relevance of the plaque shape has been emphasized
      by pathoanatomic studies in the late 1970s. The in vivo assessment of the plaque
      shape using coronary angiography has major limitations: The lumen silhouette
      obtained by angiography does not accurately reflect the histologic extent of the
      plaque due to compensatory vessel enlargement, atrophy of the media, and diffuse
      plaque accumulation. In contrast, intravascular ultrasound (IVUS) allows direct,
      cross-sectional visualization of the plaque. Although this method has a small,
      but definite acute risk, it provides the first technique for in vivo assessment
      of the extent and shape of coronary plaque. In agreement with prior pathoanatomic
      investigations, IVUS studies have confirmed that the majority of advanced
      coronary plaques are located eccentrically in the vessel and that non-diseased
      wall segments are often present in these lesions. Using IVUS imaging, it has also
      been proven that in vivo relaxation of advanced coronary stenoses by vasodilatory
      drugs is mainly based on expansion of the non-diseased wall segment. IVUS studies
      have also shown that the presence of non-diseased wall segments may be important
      for the effect of intracoronary interventions: Balloon angioplasty of eccentric
      coronary lesions often causes dilatation of the non-diseased wall segments;
      immediate and chronic elastic recoil of these vessel segments may diminish the
      lumen gain from this procedure. During directional coronary atherectomy IVUS
      imaging of the exact location and shape of the plaque may limit subintimal tissue
      retrieval and thereby also reduce restenosis.

PMID- 7810186
TI  - [Directional coronary atherectomy: effect of vessel size on primary results and
      long-term results].
AB  - Of 325 consecutive patients undergoing DCA, 263 patients with 277 stenoses were
      successfully treated with DCA alone and had angiographic follow-up 3-6 months
      later. Depending upon the initial reference diameter (RD) patients were divided
      into two subgroups: group I (n = 159) with a RD > 3 mm and group II (n = 104)
      showing a RD < or = 3 mm. In contrast to other series DCA was predominantly
      performed with 7F atherectomy devices using balloon inflation pressures of
      approximately 5 atm. Angiographic data including the minimal luminal diameter
      (MLD), percentage of stenosis (%D) and reference diameter (RD) were assessed by
      quantitative computer-assisted analysis before (pre), after (post) DCA and at a 3
      6 months angiographic follow-up (FU). The percentage of diameter stenosis
      pre/post/FU in group I was 59.9 +/- 12.6%/18.4 +/- 12.8%/29.8 +/- 17.6%, and in
      group II 55.6 +/- 10.8%/17.8 +/- 12.3%/33.7 +/- 16.1% with a net gain at FU of
      1.0 +/- 0.89 mm for group I and 0.86 +/- 0.66 mm for group II. Based on an
      angiographic restenosis criterion of at least 50% diameter obstruction at FU and
      or recurrence of symptoms warranting interventional re-treatment of the target
      lesion, the incidence of restenosis in group I was 20.6% and in group II 28.0%
      (p: n.s.). There was no significant difference between the two groups concerning
      complications. Our data show that DCA leads to a satisfying long-term
      result.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7810187
TI  - [Results of immediate and delayed bypass operation in PTCA emergencies].
AB  - The therapeutic strategy for irreversible coronary occlusion as a complication of
      PTCA is influenced by the rate of myocardial infarctions and mortality after
      emergency bypass surgery. If immediate bypass operation cannot prevent myocardial
      infarction, medication will be the treatment of choice. Since the duration of
      ischemia is of critical importance for the preservation of myocardium, we
      analyzed our results with respect to the time interval from the onset of ischemia
      to surgery. From 12/84 to 12/93 there were 49 emergency operations for 4,478
      PTCAs. In 38 patients acute closure occurred in the cath lab; because of very
      strict standby arrangements these patients could be brought to the operating
      rooms without delay (group A). In 11 patients acute closure occurred during the
      following 24 hours in the intermediate care unit (group B); attempts of catheter
      recanalisation and/or preparation for surgery accounted for an additional time
      delay until surgery of 79 minutes. RESULTS: In the 38 patients of group A there
      were only one small transmural (CKmax 533/U/l) and four non-Q wave (CK-max 322
      U/l) myocardial infarctions. Of the 11 patients in group B only two did not
      suffer any loss of myocardium. In seven cases there were transmural (CKmax 1,296
      U/l) and in two cases non-Q wave (CKmax 721 U/l) myocardial infarctions. Two
      patients of group B died on the second and third postoperative day. Thus the
      results of emergency bypass operations were excellent if surgery could be
      performed immediately after failure of catheter interventions (all survived, no
      transmural M.I. in 97%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7810188
TI  - [Value of smoking cessation, physical training and psychological interventions in
      secondary prevention of coronary heart disease].
AB  - Smoking, physical inactivity, and psychological traits may have substantial
      impacts on the development and progression of coronary heart disease. In the
      secondary prevention of coronary heart disease quitting smoking presents the most
      effective single means. In numerous studies cardiac and total mortality of ex
      smokers was reduced by 40-60% when compared to continuous smokers; this effect
      remained stable over the years or even increased. Regular physical activity is
      associated with a variety of coronary and cardioprotective mechanisms. Meta
      analyses of controlled studies demonstrated a significant reduction in cardiac
      and total mortality by rehabilitation measures which included physical training.
      However, this effect diminished in the following years. Psychological measures
      can lower cardiac risks via several mechanisms. In two major controlled secondary
      prevention trials interventions aiming at psychological changes such as
      modification of "coronary prone" type A behavior or application of "stress"
      reduction measures resulted in a significant decrease in the number of clinical
      cardiac events during the treatment phase; however, data on the long-term effects
      beyond the intervention period are still insufficient. In conclusion, in the
      secondary prevention of coronary heart disease besides strict abstention from
      smoking a continuous physical training and eventually psychological care in
      special heart groups of as many qualified patients as possible seems
      recommendable.

PMID- 7810189
TI  - [Direct effects of estrogens on vascular tone: characterization and clinical
      significance].
AB  - Estrogen replacement therapy has been found to reduce the incidence of cardio-
      and cerebrovascular diseases in postmenopausal women. The mechanisms of this
      vasoprotection are controversial. In recent years, direct vascular actions of
      estrogens have been proposed in addition to beneficial effects on cardiac risk
      factors such as hypercholesterolemia. In an attempt to determine the role of
      direct hormonal influences on human arteries we analyzed the acute vascular
      responses to 17 beta-estradiol in a series of in vitro and in vivo studies. A
      dose-dependent estrogen-induced vasorelaxation was found in human coronary
      arteries in vitro which was more pronounced in women and associated with a
      significant increase in cyclic AMP and cyclic GMP content. This vascular response
      could be confirmed in healthy postmenopausal women during a clinical double-blind
      cross-over study using a quantitative duplex-sonographic approach. Estradiol
      induced a significant vasodilation and increase of blood flow in femoral
      arteries, whereas placebo had no effect. As measured by quantitative coronary
      angiography, high-dose estradiol application was also followed by a significant
      dilation of epicardial coronary arteries. These direct vascular actions such as
      vasodilation and increase of blood flow may contribute to the preventive estrogen
      effects on cardiovascular diseases in postmenopausal women.

PMID- 7810190
TI  - [Evaluation of the aorta and supra-aortic vessels with spiral CT and 3
      dimensional vascular reconstruction after operation of aortic isthmus stenosis].
AB  - Aneurysm formation, restenosis, and hypertension are well known complications
      after surgery for coarctation of the aorta (CoA). In order to assess long-term
      results, 46 patients were studied by spiral computed tomography and three
      dimensional reconstruction after an interval ranging from 1 to 21 years (median
      10 years) after surgery for coarctation. Spiral computed tomography showed
      pathological changes of the aorta in the majority of patients. Typical findings
      were ectasy or aneurysm formation of the ascending aorta, hypoplastic aortic
      arch, ectasy or aneurysm formation of the supraaortic vessels, circumscript
      aneurysm of the descending aorta at the side of surgery, restenosis of the
      descending aorta and malformations and anomalies of arterial vessels. In order to
      initiate adequate treatment of such specific complications as restenosis,
      aneurysm and/or arterial hypertension, regular controls are necessary in patients
      after surgery for aortic coarctation. In addition to clinical examination and
      besides magnetic resonance imaging and angiography, spiral computed tomography is
      an effective non-invasive imaging method for follow-up.

PMID- 7810192
TI  - [Recommendations for independent use of transesophageal echocardiography.
      Committee of Clinical Cardiology of the German Society of Cardiology-
      Cardiovascular Research e.V].

PMID- 7810191
TI  - [Analysis of the pressure-surface relation of the left ventricle with automatic
      echocardiographic contour detection].
AB  - Echocardiographic automatic border detection is a new on-line technique
      determinating the interface between blood and myocardial tissue thus having the
      potential to calculate cyclic changes in left ventricular cavity area in real
      time. It was the main purpose of the current study to evaluate left ventricular
      pressure-area relationship after administration of nitrates. In 12 patients with
      normal left ventricular function pressure-area relation was studied after a Swan
      Ganz thermodilution catheter was placed in the wedge position and a high fidelity
      pig tail catheter was placed in the left ventricle. Left ventricular pressure and
      cyclic changes of cavity area were simultaneously analysed and displayed together
      as waveforms on the echo screen using a computer interfaced with the echo
      machine. All measurements were done before and five minutes after administration
      of 0.8 mg nitroglycerin. Mean systolic and diastolic blood pressure decreased
      significantly from 145/12 mmHg to 127/8 mmHg (p < 0.05). Mean systolic area
      decreased slightly from 10 cm2 to 9 cm2 (n.s.) whereas mean enddiastolic area
      decreased significantly from 18 cm2 to 15 cm2 (p < 0.05). Accordingly there was a
      downward and leftward shift of the diastolic pressure-area relationship following
      administration of nitroglycerin. CONCLUSION: Echocardiographic automated border
      recognition seems to be a promising new on-line method in the detection of left
      ventricular cavity area changes underlining its potential usefulness in the
      evaluation of left ventricular performance.

PMID- 7810193
TI  - [Legal issues in gerontology].

PMID- 7810194
TI  - [The elderly as victims of violent crime].
AB  - Up to now, victimology has only dealt with partial aspects of the situation of
      the elderly as victims of violent crime. Nevertheless, the Police Crime
      Statistics enable us to make the following three basic statements: In general,
      old people are less likely to become victims of violent crime (than young
      people). The acts of violence committed against the elderly are mainly ones in
      which there was a relationship between offender and victim before the offense.
      Elderly women are disproportionately more often victims of purse snatching. The
      increasing social isolation of old people constitutes not only a specific form of
      victimization, it probably also increases their susceptibility to become victims.
      The theory that old people have "a particularly pronounced fear of crime" cannot
      be generally proven. This question must be considered from differing points of
      view and depends largely on the individual vulnerability of the old people. In
      Germany, there has hardly been any empirical study of violence towards the
      elderly in institutions and in family households (so-called domestic violence).
      It is believed that more violence takes place in both than in generally assumed.

PMID- 7810195
TI  - [Information about medical procedures involving elderly patients].
AB  - Physicians are obliged to inform all patients about the diagnosis and course as
      well as the purpose and risks of diagnostic and therapeutic procedures.
      Difficulties in informing elderly, especially cognitively impaired patients are
      discussed. The legal aspects in Germany are shortly reviewed.

PMID- 7810196
TI  - [Homicides involving the elderly].
AB  - At the Institute for Legal Medicine in Hamburg, 105 cases of homicide among the
      elderly (> or = 65 years of age) have been analyzed. The study shows typical
      characteristics in personal and social conditions of victims and offenders. The
      problem of victimization is described. Finally, preventive measures are
      discussed.

PMID- 7810197
TI  - [Traffic accident fatality involving the elderly as passengers].
AB  - At the Institute for Legal Medicine in Hamburg, 54 car and bus accidents
      involving elderly people (age > or = 65 years) over the last decade have been
      studied. Differences in sex and age, the reasons for accident and death, and
      specific problems of clinical therapy are analyzed. Mostly men had been the
      drivers, half of them being personally responsible for the accident. Special
      psychophysical factors associated with old age could not be identified as
      causative factors for the accidents within this series.

PMID- 7810198
TI  - [Current legal principles for geriatric rehabilitation].

PMID- 7810199
TI  - Levels of trace elements in blood in healthy aging subjects.
AB  - The effects of age and sex on the serum levels of trace elements were determined
      after an overnight fast in 80 ambulatory, disease-free adults who had undergone
      rigorous health screening. Significant age and sex differences were found for Mn.
      Blood levels of Cu and Zn showed both age and sex differences. No age or sex
      differences were found for Pb, Cd, Cr, Ni, Se, and Al.

PMID- 7810200
TI  - Age-related calcium/magnesium ratio in the ligamenta flava.
AB  - The Ca/Mg ratio in fibrous connective tissue may be related to its elastic
      property. Ligamenta flava were obtained from 76 patients during lumbar disc
      surgery, and Ca and Mg levels were determined by atomic absorption spectrometry.
      The Ca/Mg ratio was almost constant throughout all age groups. It is concluded
      that the constancy of the Ca/Mg ratio throughout the lifetime is an integral
      quality of elastic fibers which may be explained by the biological long half-life
      of elastin.

PMID- 7810201
TI  - Deficient repair of UV-induced DNA damage in immature human T cells.
AB  - As compared with quiescent lymphocytes, human thymocytes were found in the
      nucleoid sedimentation assay to be deficient in UV-induced DNA repair. Therefore,
      the age-related repair deficiency of human lymphocytes can result from the
      increased proportion of immature T cells occurring with age.

PMID- 7810203
TI  - [A systematic genetic-epidemiologic family study of patients with Alzheimer
      disease--experience with the MIRAGE study in Germany].
AB  - A register of the families of 60 patients with Alzheimer's disease was
      established with two questionnaires (the Family History Questionnaire and the
      Patient History Questionnaire). These questionnaires, instruments of the MIRAGE
      study, were translated into German. 35% of the families had more than one family
      member affected with dementia. The frequencies of the risk factors that were
      studied were surprisingly high. The responses of the family members to the study
      were very positive and encourage further investigation in the field of genetic
      epidemiology in Alzheimer's disease.

PMID- 7810202
TI  - [Indications spectrum for temporary and permanent cardiac pacemaker therapy].
AB  - Temporary pacemaker therapy is defined as a limited electrical stimulation of the
      heart with an external generator. This method is used in emergency situations for
      patients with bradycardia or asystolia. Since the first implantation of a
      permanent pacemaker in 1958, the types of indications changed according to
      technological development of the generators. In former times, total AV-block of
      the heart was the classical indication. Today, also patients with bradyarrhythmia
      or sinus node dysfunction are given a pacemaker based on hemodynamic findings.
      More possibilities in pacemaker programming also requires more education of
      physicians.

PMID- 7810205
TI  - [The genetic traits of the spatial organization of the electrical activity of the
      human cerebral cortex].
AB  - Within-pair similarity of topographic maps of the cortical electrical activity
      was studied in 11 monozygotic pairs of twins (MZ) and 20 genetically unrelated
      persons (UP) during rest and solving four mental tasks. During rest similarity of
      topographic maps higher in MZ in comparison with UP. We showed that no specific
      frequency band influenced formation of high similarity between MZ maps. The
      maximal similarity between MZ maps was seen in the anterior zones of the left
      hemisphere and in parieto-temporal areas of the right hemisphere. Differences
      between MZ and UP maps were revealed both in the anterior areas of the left
      hemisphere and parieto-temporal areas of the right hemisphere, but they were most
      pronounced in the right hemisphere. The data obtained lead to the conclusion that
      genetic factor influences not only the separate EEG components, but the system
      organization of the cortical processes. This was confirmed by the results of
      topographic similarity analysis carried out for various tasks, i.e. similarity
      coefficients attained the level of significance only for the right-hemispheric
      tasks (simultaneous analysis of non-verbal material).

PMID- 7810204
TI  - [Consciousness as a system of inner seeing].
AB  - The goal of the paper is to clarify the nature and mechanisms of functioning of
      human consciousness. It is assumed that the main specific feature, which
      distinguishes consciousness from other brain subsystems, is its ability to
      observe the content of its own memory. It demonstrates that cyclic information
      run in distributed neural structures with feedbacks may serve as a fundamental
      physiological mechanism of an inner scanning (awareness) system for information
      coming from outside. The area of location of consciousness in the brain is
      determined as a set of neural structures involved in cyclic information run
      processes. It is ascertained that the rehearsal procedure is a basis operational
      means of discursive thinking, imagination and reflexion.

PMID- 7810206
TI  - [A comparative analysis of the brain activity during the traditional and
      intensive forms of learning foreign languages].
AB  - By means of dichotic test the comparative research of the brain activity in
      dynamics in 84 adult students was conducted during their traditional (36 persons)
      and intensive (48 persons) learning of foreign languages. By different methods of
      learning the reliable distinction of the hemisphere's asymmetry was not detected.
      By both methods in the reliable majority of students the activation of the
      hemisphere opposite to the one dominating initially was observed. The correlation
      between the maximum quantitative shift of the right ear coefficient and the level
      of success in colloquial practice by the same initial level of language start and
      initial comparable size of memory was revealed. The authors discuss the
      possibility of the individual map composition for every student using the results
      of dichotic tests in dynamics for the help in the profession of a teacher.

PMID- 7810207
TI  - [The effect of the duration of mental work on problem solving in mental
      rotation].
AB  - Effect of sustained mental work on the first stage of mental rotation was studied
      by the method of intracortical interaction. It was revealed that during sustained
      mental work the zone of the high level of connections in the alpha-band was
      considerably reduced due to an increase of specificity, rationality of thinking.
      In the beta-band the zone of the high connection level moved from the central and
      parietal areas to the anterior regions because of a switch of intention of the
      mental work from the spatial analysis to the quick verbalization of the response.
      Tired subjects in search for a word for the response did not fulfil the spatial
      analysis of the pictures. Subjects with high working ability searched for the
      verbal response on the basis of mental operations with images, that turned to be
      optimal for the mental rotation task solving.

PMID- 7810208
TI  - [The topography of the afferent and efferent flows in the mechanisms of auditory
      selective attention].
AB  - Auditory evoked potentials (AEPs) were recorded in 10 adult healthy subjects
      under conditions of simple rhythmical stimulation and during solving selective
      attention task. Middle- (10-60 ms) and long-latency (up to 400 ms) AEPs were
      analysed by AEP mapping and by evaluation of their spatio-temporal
      characteristics. it is suggested that interaction between the parietal, left
      temporal and left frontal cortical areas exerts efferent influence to brainstem
      structures over a period of 15-35 ms. Amplitudes of P90 and P250 components were
      reduced during selective attention task. The late P350 component increases,
      mainly, in the central and frontal cortical areas.

PMID- 7810209
TI  - [THe characteristics of the autonomic reactions of healthy adolescents and of
      those with lowered intellectual productivity].
AB  - Present research is devoted to psychophysiological study of the mechanisms of
      functional state control in normal and educationally disabled children using EEG,
      neuropsychological, and heart rate data obtained during different types of mental
      activity, including performance of arithmetic, verbal, spatial, and time
      perception tests. Attention index and one-minute time interval production in the
      group of educationally disabled patients were found to be statistically lower
      than in the normal children. Heart rate level in this group was also lower than
      in the normal children of the same age. Increase of heart rate indices during
      perception of instruction and transition to its realization was statistically
      higher in the group of normal children. The differences between the groups can be
      explained by disfunction of the functional state regulation mechanisms, deficit
      of sympathetic influence and prevalence of parasympathetic ones, as well as by
      the weakness of the functions of the nervous system which causes disadaptation in
      educationally disabled children.

PMID- 7810211
TI  - [The differential effect of damage to the motor cortex on the precise reactions
      of avoidance and escape in dogs].
AB  - Effects of ablation of the forelimb area in the motor cortex on the precise
      lifting of this limb were studied. Even inaccurate avoidance reactions to the
      sound signal did not recover spontaneously. In the course of retraining irregular
      reactions of insufficient amplitude could be easily recovered but the precise
      reactions (both fast continuous and slow discontinuous) did not recover at least
      for half a year after the ablation. On the contrary, the fast precise escape
      reactions (to the shock applied to the "working" limb and eliciting its
      unconditioned flexion) remained essentially unchanged, i. a. the ability to stop
      movement in the correct (previously learnt) position persisted. The ability to
      fix position of the flexed limb retained but in was less perfect and did not
      improve. The ability to overcome unconditioned flexion (in order to perform
      discontinuous extensor escape reaction) was severely and continuously (for a
      year) decreased. Visually guided placings of the forepaw on a held out hand of an
      experimenter recovered essentially spontaneously and almost completely during a
      month.

PMID- 7810210
TI  - [The effect of neuropeptides on the processes of higher nervous activity in
      primates. The action of cyclic analogs of enkephalins on the behavior of lower
      monkeys].
AB  - The influence of 2 cyclic enkephaline analogues (IVS-43 and IVS-46) on group and
      individual behaviour of rhesus and baboon monkeys was studied. The effect of IVS
      46 on competitive and operant goal-directed behaviour of the monkeys was
      expressed. Possible mechanisms of functional reorganization of the higher nervous
      activity of primates under the influence of neuropeptides are discussed.

PMID- 7810212
TI  - [The dynamic shifts in the parameters of the traditional frequency-range of the
      EEG during learning in dogs].
AB  - Parameters of EEG recorded from some areas of the cortex and olfactory bulbs were
      studied during lever-pressing alimentary conditioning in dogs and analysed using
      FFT in a wide frequency range (1-100 Hz). Parameters of electrical activity in
      the cortex ans olfactory bulbs were shown to have different dynamics. Power level
      of cortical potentials increased in the high frequency band (40 Hz and upwards)
      and that of the olfactory bulbs increased in both high frequency and alpha bands.
      Coherent-phase characteristics of the cortical potentials give evidence that in
      the process of conditioning more stable relations establish between activities of
      different cortical areas in both high frequency and alpha bands than in the state
      of quiet wakefulness. At the same time relations between potentials in the cortex
      and in the bulbs were characterized by the larger phase shifts, increase of
      coherence attributed only to the high frequency but not traditional bands.
      Possible role of the alpha frequencies along with the high frequency band in the
      process of information processing is discussed.

PMID- 7810213
TI  - [The effect of dilantin on the neuronal reactions of the sensorimotor cortex and
      hippocampus during learning].
AB  - After dilantin (D) administration in a dose which reduced posttetanic
      potentiation (according to the data of literature), probability of movements to
      light flashes (conditioned signal of a defensive reflex) did not change. Weak but
      stable disinhibition of motor reactions to flashes was observed when they were
      presented at the background of continuous light as a conditioned inhibitor.
      Activation of neurons of the sensorimotor cortex in response to reinforced and
      non-reinforced light flashes increased under D action (as it had been earlier
      observed in neurons of the visual cortex), and activatory reactions to pain
      reinforcement decreased. In hippocampal neurons increase of the rate of
      impulsation in response to reinforced flashes under the action of D disappeared.
      On the basis of the data obtained it can be concluded that PTP in the neocortex
      does not participate in long-term memory storage of the biological significance
      of activating stimulus.

PMID- 7810214
TI  - [The theta rhythm of the rat hippocampus as a nonlinear dynamic process].
AB  - The theta rythm of the rat's hippocampus in paradoxical phase of sleep and in
      orientational behavior is investigated by estimating the attractor's dimension.
      It is shown that the theta rhythm of the hippocampus consists of a regular
      component and an irregular one of high dimension which relation is in the wide
      variation depending on the state of the animal. The frequency characteristics of
      both components are revealed as well as the mechanisms of their forming. Some
      hypothesis that concern their biological nature are suggested.

PMID- 7810216
TI  - [The spatial-temporal organization of cortical neuronal functions in a
      conditioned reflex to time].
AB  - Multiunit activity in the motor cortex of cats was analysed during food-procuring
      conditioning to time (2-minute interval). Comparison of behavioural and
      neurophysiological correlates at the initial stage of conditioning showed that it
      was accompanied by very complicated system transformations which were different
      for neuronal micro- and macrostructures. Systemic processes in the micro- and
      macroareas were distinguished by a specificity of space distribution, quantity,
      strength, and stability of manifestations of functional connections. Capability
      of neurons for functional orientation, increase of percentage of incidence of
      functional connections in the second half of the conditioned interval,
      considerable destabilization of all neuronal associations at the last and highest
      stage of conditioning were the common features for micro- and macroareas during
      formation of the food-procuring conditioned response.

PMID- 7810215
TI  - [The food-acquisition behavior of rats under conditions of the chronic activation
      and blockade of the neostriatal dopaminergic system].
AB  - Effects of three-week daily intrastriatal amphetamine (15 and 45 mcg) and
      haloperidol (5 mcg) microinjections were studied in rats in a Skinners's box.
      Enhancement of motor activity, stereotype movements, increase of rate of lever
      pressings were recorded at the background of amphetamine microinjections in a
      dose of 45 mcg. In animals with initially low level of conditioning dopaminergic
      striatal stimulation qualitatively changed behavioural strategy, which promoted
      the stable long-term activation of instrumental conditioning. Amphetamine in a
      dose of 15 mcg was ineffective. Haloperidol had the opposite effects, i. e., it
      impaired conditioned alimentary behaviour and induced parkinsonian-like akinetic
      status. The findings suggest an involvement of dopaminergic neostriatal system in
      conditioned food-procuring behavioural strategy.

PMID- 7810217
TI  - [The modulation of septal influences on the hippocampal neurons by cholinergic
      substances].
AB  - To evaluate the functional significance of the cholinergic component of the septo
      hippocampal input the effects of electrical stimulation of the medial septal area
      (MS--DB) on the hippocampal neurons were studied in chronic waking rabbits.
      Initial inhibitory effects 40-140 msec long were observed in 54% of neurons in
      intact rabbits. Other neurons usually responded by a diffuse excitation. Initial
      inhibitory effects absolutely dominated (90%) in the animals with the septum
      basally undercut. Increase of the endogenous acetylcholine level by physostigmine
      completely or partially blocked the effects of the stimulation in 78% of the
      hippocampal neurons at the background of increased theta-modulation. Scopolamine
      restored responsiveness of the neurons to the MS--DB stimulation. These effects
      were preserved in the animals with the septal undercutting. It is concluded that
      the general effect of the MS--DB on the hippocampal neurons consists in a non-
      cholinergic (GABA-ergic) primary suppression (reset) of their activity. The
      cholinergic component limits the efficacy of both extraseptal (brainstem) and
      septal inhibitory influences.

PMID- 7810218
TI  - [Excitatory interactions in the nerve nets switching on the cells of the auditory
      cortex and the medial geniculate body].
AB  - Crosscorrelation method was used for revealing effective monosynaptic excitatory
      interactions in neural networks containing simultaneously recorded neurons from
      different loci of auditory cortex (A1) and medial geniculate body (MGB). It was
      shown that (a) there were effective reciprocal excitatory connections between
      neurons in different loci of A1 and MGB; (b) connections between neurons in
      tonotopic loci of A1 and MGB and in adjacent cortical loci were the most
      effective; (c) connections were "divergent", i.e., one neuron in A1 (MGB) excited
      neurons in different loci of A1 and MGB simultaneously; (d) connections were
      "convergent", i. e., one neuron in A1 (MGB) was excited by neurons from different
      loci of A1 and MGB simultaneously. We suggest that this principles of
      organization of excitatory connections in thalamo-cortical networks promoted the
      induction of long-term changes (LTP and LTD) in excitatory synaptic efficacy and
      that this mechanism underlie the observed changes of receptive fields of A1 and
      MGB neurons induced by intracortical microstimulation.

PMID- 7810219
TI  - [The role of the limbic cortex in regulating the neuronal impulse activity of the
      respiratory center in the medulla oblongata under conditions of oxygen
      deficiency].
AB  - Complex action of hypoxia and electrostimulation of the limbic cortex on unit
      activity of bulbar respiratory neurons was studied. Under normal barometric
      pressure the influence of the limbic electrostimulation on activity of bulbar
      respiratory neurons was ambiguous, i.e., both activation and inhibition were
      observed, but inhibitory influences prevailed. In initial phase (4000-5000 m) at
      the background of hypoxic activation the influence of electrostimulation of the
      limbic cortex on activity of respiratory neurons was predominantly inhibitory, as
      under conditions of normoxia. In the phase of severe hypoxia (7500-8000 m) at the
      background of expressed hypoxic suppression of activity of respiratory neurons
      stimulation of the limbic cortex did not induce reactions characteristic of these
      neurons. Reaction of the respiratory neurons on the electrical stimulation of the
      limbic cortex in different phases of hypoxic action depended on relatively high
      sensitivity to hypoxia of the limbic cortex and the functional state of the
      bulbar respiratory center.

PMID- 7810220
TI  - [The naloxone-dependent effects of the psychostimulant sidnofen: a study on
      identified neurons of the snail].
AB  - Excitatory and oscillogenic action of psychostimulant sydnophen on identified
      serotoninergic and peptidergic neurons was shown in the Helix brain. Sydnophen
      induced marked depolarizing shift, increase of the firing activity, activated
      excitatory synaptic input and generation of endogenous slow depolarizing
      potentials and burst activity in these neurons. The effect of sydnophen was
      blocked by naloxone and was imitated by the agonists of opiate receptors morphine
      and met-enkephalin. Majority of the other studied identified and non-identified
      neurons in the Helix brain did not react to sydnophen. Selective naloxone
      dependent effect of sydnophen and the possible role of endogenous opioid system
      in the action of psychotropic agents are discussed.

PMID- 7810222
TI  - [Long-term rearrangements of the processing of kinesthetic afferentation at the
      neuronal level of the cat motor cortex after damage to the ventrolateral thalamic
      nucleus].
AB  - Single-unit recordings from motor cortex (area 4) were obtained in cats and under
      semichronic experimental conditions before and within various periods (from a
      week to five months) after the lesion in thalamic nucleus ventralis lateralis (n.
      VL). Neuronal responses to tactile stimulation of the contralateral forelimb and
      its passive movement in the wrist joint with the mean speed 170 degrees/s were
      studied. As it had been already reported by others, the magnitude and time course
      of averaged response histograms for some neurons, which were evoked by imposed
      displacements of the forelimb, were related to the velocity and/or acceleration
      components of the movements. Spontaneous firing and kinematic processing
      capabilities of motor cortical cells were affected by the lesion. The findings
      are in agreement with a hypothesis that n. VL is essential for encoding specific
      kinematic features of angular joint movements. Restoration of kinematic
      processing by cortical neurons in the course of post-traumatic period was
      characterized by facilitation of activatory reactions of the area 4 cortical
      cells to peripheral cutaneous stimulation. Some suggestions are made on the
      nature of plastic changes which develop in neuronal nets of the motor cortex
      after the lesion of n. VL.

PMID- 7810221
TI  - [The plasticity of the snail cholinoreceptor neurons following exposures to the
      inositol 1,4,5-triphosphate- and Ca2(+)-dependent mobilization of deposited
      Ca2(+) and the level of phosphatidic acid].
AB  - Effects of some substances (which influence on mobilization of deported Ca2+ and
      intracellular level of second messengers) on identified neurons RPa3 and LPa3 of
      Helix lucorum were studied using two-electrode voltage clamp technique. The
      action of inositol-1,4,5-trisphosphate (IP3), inositolhexakisphosphate (IP6), TMB
      8 inhibitor of IP3-dependent Ca2+ mobilization), tetracaine (inhibitor of Ca(2+)
      dependent mobilization of Ca2+), and phospholipase D (which catalyzes
      phosphatidic acid formation from membrane phosphatidylcholine) was studied.
      Participation of IP3, IP3-dependent-, Ca(2+)-dependent mobilized intracellular
      Ca2+ and phosphatidic acid in regulation of cholinoreceptor plasticity was shown
      in Helix neurons.

PMID- 7810223
TI  - [The synaptic proteins of the temporal associative area in the neocortex (field
      Ep) of cats with normal and decreased cognitive capacities].
AB  - Fractions of light and heavy synaptosomes were prepared from associative temporal
      area of cat brain, which were previously tested behaviorally for ability to solve
      the generalization, gnostic and abstraction tasks. The synaptic membrane
      subfractions and synaptoplasma fractions were isolated and the content of the
      total protein and of the demasked protein sulfhydryl groups (SH groups) was
      investigated spectrophotometrically. The maximal content of the demasked SH
      groups was revealed in the upper subfractions (mainly the membranes of
      cholinergic synapses) and minimal content--in the lower subfractions (mainly
      noncholinergic synapses). Significantly smaller total protein content in the
      upper and middle subfractions of light synaptosomes was found, and more demasked
      SH groups in the membrane-bound proteins of the upper and middle subfractions of
      light and heavy synaptosomes was found in the cortex area of the "clever" then
      "silly" cats. Suggestion concerning characteristic for brains of "clever" cats
      relatively low total quantity of synapses in the area Ep of the cortex and
      significantly higher proportion of cholinergic ones is discussed.

PMID- 7810224
TI  - [The characteristics of the anticonflict action of fenazepam in rats selected by
      the method of forced swimming].
AB  - A method of classification of outbred albino rats by means of forced swimming in
      a tank filled with water and equipped by freely turning wheels was developed.
      Using this technique a population of albino rats can be divided into three
      groups: highly active (HA), low active (LA) animals, and rats with intermediate
      activity. HA animals exhibit stable behaviour in forced swimming and conflict
      situation paradigms. They are also more sensitive to a benzodiazepine anxiolytic
      phenazepam in conflict situation test. At the same time, LA rats decrease their
      activity and are less sensitive to phenazepam. Both groups (LA and HA) are not
      homogeneous: each of them includes animals demonstrating quite another type of
      behaviour compared with a majority of rats.

PMID- 7810225
TI  - [The neurohormonal characteristics of rats selected for the duration of the
      passive defense reaction and for the threshold of neuromuscular excitability].
AB  - Two strains of rats, "genetic catalepsy" and "low-threshold", simulating some
      human psychopathological symptoms, were compared. Levels of brain monoamines and
      blood corticosterone and testosterone showed no common features in the strains
      studied. The levels of dopamine in amygdala and testosterone blood levels in rats
      of the two strains significantly deviated in opposite directions from
      corresponding controls. In "genetic catalepsy" strain noradrenaline content in
      striatum and diencephalon was decreased, and serotonin striatal level was
      increased.

PMID- 7810226
TI  - [The effect of deprenil on the dopaminergic system of the brain in mice of
      different genotypes during aging].
AB  - Effects of aging on brain dopaminergic system, e.g., neurotransmitter metabolism
      and different kinds of dopamine-dependent behaviour, were studied in mice of
      three inbred strains. Homovanillic acid concentrations in structures of both
      nigrostriatal (striatum) and mesolimbic (n. accumbens with tuberculum
      olfactorium) systems were found to be increased in the aged animals. Aged mice of
      the strains studied were characterized by decreased locomotor activity and
      stereotypic climbing; CC57Br mice, in contrast to A/He and C3H/He, demonstrated
      significantly diminished level of investigatory activity. However, genotypic
      differences in these kinds of behaviour were less pronounced in the aged animals
      in comparison to the young adults, but interstrain differences in swimming
      activity (Porsolt's "despair test") which was almost unchanged in aged mice,
      remained enough pronounced. In the aged mice postsynaptic dopamine receptor
      sensitivity, assessed after administration of a high dose of the mixed agonist
      apomorphine, was markedly decreased. Chronic treatment with deprenyl, a specific
      MAO-B inhibitor, produced a clear-cut genotype-dependent effect on investigatory
      activity in the aged animals. High level of this activity, characteristic for the
      young adults, was restored in CC57Br, in A/He it was elevated in comparison both
      with young and old untreated animals, and the same tendency was observed in
      C3H/He. This fact seems to reflect an interesting property of deprenyl to
      increase general adaptation in the aged organism, that might have valuable
      clinical implications.

PMID- 7810227
TI  - [The role of the activation of the intralaminar thalamic nuclei in regulating the
      participation of the neostriatal cholinergic system in the differentiation of
      sound signals by dogs].

PMID- 7810228
TI  - [The characteristics of the acquisition of motor-food conditioned reflexes in
      dogs during the creation of a motivational dominant of hunger].

PMID- 7810229
TI  - [The spectral changes in cortical electrical activity during stimulation of the
      locus coeruleus in rabbits].

PMID- 7810230
TI  - [The effect of serotonin on the rate of plastic processes in the hippocampus].

PMID- 7810232
TI  - [The use of the point mapping method for the frequency evaluation of the global
      and local changes in the spatial-temporal organization of the electrical activity
      of the human brain].

PMID- 7810231
TI  - [The potentiating action of vasopressin is not blocked by ketamine].

PMID- 7810233
TI  - [The use of the correlation pleiad method for the analysis of the behavioral
      parameters of a genetically heterogeneous group of mice].

PMID- 7810234
TI  - [From the archival materials of A. A. Ukhtomskii].

PMID- 7810235
TI  - [Apropos the applicability of the basic laws of nature to complex biological
      objects].

PMID- 7810236
TI  - [The etiopathogenetic significance of vitamin D3 in osteoarthropathia
      psoriatica].
AB  - 1.25 (OH)2 D3 is the most effective natural metabolite of vitamin D. By binding
      to a specific receptor (VDR) it develops genomic as well as non genomic effects
      which exceed the effects on calcium regulation. Exercising an influence on
      immunological phenomena and on the behavior of cellular differentiation and
      proliferation, the different manifestations of psoriatic osteoarthropathy (skin
      lesions, chronic synovialitis, increased bone remodeling) may be due to a common
      pathogenetic process of a disturbed vitamin D metabolism. However, the supposed
      fault has not yet been defined and this concept is still hypothetical. Moreover,
      it is probable that it represents a partial aspect only in the quite unclear
      pathogenesis of the disease.

PMID- 7810238
TI  - [The significance of inflammatory changes in the tarsometatarsal joints for
      development of rheumatic splayed foot: a radiologic follow-up].
AB  - The involvement of foot joints is a common finding in more than 90% of the
      patients with rheumatoid arthritis. The typical deformity of the forefoot is the
      splayfoot with hallux valgus or hallux rigidus and deformities of the lesser
      toes. 70 feet of 36 patients with rheumatoid arthritis were observed
      radiologically over a period between 5 years/1 month and 6 years/1 month. The x
      rays were analyzed for arthritic changes of the various joints and changes of the
      foot statics. The question was whether the splay of the forefoot is caused by an
      arthritis of the metatarsophalangeal or tarsometatarsal joints with a consequent
      weakening of joint capsules and ligaments, or statistically by a flattening of
      the longitudinal arch owing to arthritic changes of the hindfoot. The statistic
      analysis showed that the splay of the forefoot appears between the first and
      second metatarsal bones. The arthritis of the tarsometatarsal joints II-IV could
      be identified as a statistically significant factor for the development of a
      splayfoot in rheumatoid arthritis. The influence of arthritic changes of the
      tarsometatarsal joints I and V was striking, but not statistically significant.
      The arthritis of the tarsometatarsal joints caused a flattening of the transverse
      arch already at an early stage. An arthritis of the metatarsophalangeal joints
      and the flattening of the longitudinal arch with arthritides of the rear foot had
      no statistically significant influence on the forefoot. From the results, we must
      draw the conclusions that orthopedic aids like shoe supports with retrocapital
      metatarsal bars should be recommended already at an early stage of the disease
      and that the support of the longitudinal arch is not sufficient to prevent a
      splayfoot.

PMID- 7810237
TI  - [Differential therapy of osteoporosis--an overview based on recent findings
      regarding the pathogenesis].
AB  - Osteoporosis had long been considered as an unavoidable consequence of aging for
      which no prevention was possible, whereas it has recently been recognized as a
      disease that can be prevented and treated. It is of outstanding importance to
      choose a therapy tailored to the individual patient based on new findings on the
      pathogenesis of the different types of osteoporosis and the differential
      diagnosis related to these. During phases of rapid bone loss, usually at the
      beginning of postmenopause, but sometimes also in older patients, it is useful to
      use therapeutic drugs to slow down the high bone turnover to a physiological
      level when osteoporosis is imminent or manifest. The ideal therapy of established
      osteoporosis should stimulate bone formation and increase bone mass as well as
      correct changes in the architecture so that the incidence of new fractures will
      be reduced or even prevented. In case of an increased fragility, it is especially
      advantageous to increase the cortical bone mass and to stimulate periosteal bone
      formation in particular. Therapies increasing cortical porosity such as the
      administration of fluoride in large doses weaken the bones. Therapies reducing
      bone remodeling in the long term can inhibit bone reparation and compensatory
      periosteal bone formation, however. Future prospects for the therapy of
      osteoporosis using drugs are, on the one hand, an improved exploitation of
      present strategies by means of new galenical types of application, changes in the
      daily dosage, the introduction of interval therapies, and synergistic effects due
      to suitable combinations. On the other hand, new developments achieved by varying
      chemical structures, e.g., the structures of bisphosphonates and vitamin D
      metabolites and, above all, new strategies leading to increased bone mass while
      maintaining or even improving bone structure are urgently required. In addition
      to the vitamin D metabolites, mainly the parathyroid hormone fragments and growth
      hormones seem to be promising to achieve this aim. The direct use of cytokines
      (IGF-1, IGF-2, TGF-beta, etc.) is not yet possible because there is no suitable
      "drug targeting". An increase in bone mass that has been clinically documented
      does not necessarily indicate an increased mechanical stability. Bone quality
      results from a complex relationship between bone mass, bone structure, and the
      strength of the individual structure elements. Its quantitative measurement and
      influencing by therapies will be a great challenge to future osteoporosis
      research.

PMID- 7810239
TI  - [An unusual constellation of findings in polymyositis--differential diagnosis and
      clinical course].
AB  - Clinical and biochemical findings are described in a 34-year-old female with
      atypical polymyositis. Uncommon clinical features in this patient included
      distally accented decreased muscle strength and myalgias, atypical
      electromyographic findings, a remarkable discrepancy between clinical findings
      and laboratory parameters of myolysis, unexplained episodes of somnolism,
      presence of increased serum lactate levels, and a unilateral mamma aplasia. For
      this combination of signs a polymyositis or an inclusion body myositis, but also
      a metabolic or heredodegenerative myopathy was considered. Finally, the
      idiopathic polymyositis was confirmed histologically and a marked improvement in
      the clinical and biochemical signs occurred after commencement of high-dose
      methylprednisolone.

PMID- 7810240
TI  - Rheumatoid nodules located in the penis of a methotrexate-treated patient with
      rheumatoid arthritis.
AB  - A case is reported in which a patient with a rheumatoid factor-negative
      rheumatoid arthritis developed rheumatoid nodules in the penis during treatment
      with methotrexate. The development of rheumatoid nodules in seronegative
      rheumatoid arthritis patients is extremely rare. An acceleration of rheumatoid
      nodules in methotrexate-treated rheumatoid arthritis patients is reported in
      literature. Regarding the case reported here, we propose a causal relationship
      between methotrexate-treatment and the development of rheumatoid nodules in our
      patient. Methotrexate should not be the preferential treatment for patients with
      rheumatoid arthritis developing rheumatoid nodules and suffering from vasculitis.

PMID- 7810241
TI  - [Comment on R. Rau: "A not only American controversy on the effectiveness of
      parenteral gold treatment"].

PMID- 7810242
TI  - [Puerperium after threatened premature labor--positive effects of infection
      screening by determination of CRP in pregnancy].
AB  - Silent intrauterine infection as cause of preterm labour should be recognised
      early by measuring C-reactive protein (CRP) levels in the maternal serum. Ensuing
      antibiotic therapy may not only cause gestational prolongation, but also has a
      positive effect on pathology during the puerperal period. Consequently, we
      examined the rate of infectious puerperal complications of 181 patients who
      suffered from so-called idiopathic preterm labour. 84 patients showed normal CRP
      levels at the onset of tocolysis (< 5 mg/l); an elevated level was found in 97
      patients (> 5 mg/l). Patients with elevated CRP-levels and supplemented
      antibiotic therapy during pregnancy (n = 51) showed significantly fewer symptoms
      of postpartal endometritis than women with similarly elevated CRP-levels but
      without antibiotics (n = 46). This effect was not produced when preterm labour
      was associated with normal CRP-levels. Patients with premature contractions and
      elevated CRP-values at the onset of tocolysis seem to benefit from the antibiotic
      therapy during pregnancy because they show reduced infectious complications
      throughout the puerperal period.

PMID- 7810243
TI  - Pudendal reflexes in women with pelvic floor disorders.
AB  - The objective of this work was to study two pudendal anal reflexes: Deep Pudendal
      Reflex (DPR) and classical Bulbocavernosus Reflex (BCR) in women with primary and
      recurrent genital prolapse to obtain support to the hypothesis of pelvic nerve
      damage in patients with pelvic floor disorders. 124 women were studied: 68 were
      normal; 38 with genital prolapse (GP); and 18 with recurrent GP. Clinical and
      electrophysiological studies were carried out. Delayed reflex responses were
      found in 44/56 of patients (79%). [27/38 in genital prolapse group (71%); 17/18
      in recurrent GP group (94%)]. The evaluation of pelvic floor reflex responses are
      tests to be taken into account in the diagnosis and management of pelvic floor
      disorders.

PMID- 7810244
TI  - Delayed childbearing and pregnancy outcome.
AB  - This study is to analyze the effect of delayed childbearing on pregnancy outcome
      among nulliparous women. A hospital-based study was conducted with prospectively
      collected data from the computerized perinatal data base that includes
      information about all patients delivered in our Hospital. We studied 17,230
      nulliparous women who were > or = 20 years of age with a singleton gestation
      delivered between 1987 and 1992. We assessed the rates of low birth weight (<
      2500 g), preterm delivery (< 37 weeks), small for gestational age, perinatal
      death (> 500 g and 28 days of life), and selected complications of pregnancy and
      delivery (ante partum complications, meconium, labor abnormal fetal heart rate,
      cesarean section, breech presentation, Apgar score, umbilical cord-pH, and rates
      of neonatal admission). Compared with women aged 20-29 years, women aged > or =
      35 years had no significantly higher odds ratio (OR) of low birth weight < 2500 g
      (OR = 1.3); preterm delivery < 37 weeks (OR = 1.2); small for gestational age (OR
      = 1.0); and perinatal death (OR = 1.7). In contrast, we found a significantly
      higher rates of specific antepartal complications (OR = 1.9); cesarean section
      (OR = 2.5); breech presentation (OR = 1.4); and higher rates of admission to the
      newborn intensive care unit (OR = 1.4); but excluding infants delivered before 37
      weeks of gestation, we found no significantly higher odds ratio of neonatal
      admission (OR = 1.4). Delayed childbearing is associated with an increased risk
      of complications of pregnancy and delivery although neonatal outcomes were not
      appreciably different from those among infants of younger women.

PMID- 7810245
TI  - [Tumor asepsis in organ saving pelviscopic ovarian surgery exemplified by dermoid
      cysts].
AB  - Three different surgical techniques were performed to remove ovarial tumors by
      pelviscopic organ-preserving surgery. Contamination of the peritoneal cavity with
      cystic and tumorous materia had to be prevented. Ovarian surgery was done in 112
      pre-menopausal patients. Three techniques were compared: 1. complete extirpation
      of the cyst, 2. extirpation of the cystic wall after careful irrigation of the
      cyst, 3. the 'diaphragm technique': the affected ovary is operated inside a bag.
      Contamination of the peritoneal cavity was prevented only by the 'diaphragm
      technique'.

PMID- 7810246
TI  - [Primitive neuroectodermal tumor of the uterus--a monophasic differentiated mixed
      Mullerian tumor?].
AB  - Primitive neuroectodermal tumours of the uterus are exceedingly rare. Only ten
      cases have been reported so far. A further tumour in a 63-year-old women is
      presented here with clinical and morphological results. The relationship to the
      mixed Mullerian Tumour is discussed.

PMID- 7810247
TI  - [The so-called stromatosis uteri--a low malignancy sarcoma--morphologic study
      based on 8 case reports].
AB  - Eight case reports of the so-called stromatosis uteri (SU) are presented,
      followed by explanations on pathological anatomy, immunohistochemistry,
      biological behaviour and histogenesis of this rare sarcoma entity. Finally,
      therapy is discussed.

PMID- 7810248
TI  - [Hailey-Hailey pemphigus--one only sees what one recognizes].
AB  - A diagnosis of Pemphigus Hailey-Hailey was made by histopathology after more than
      20 years of suffering and medical treatment. The lesion had almost exclusively
      affected the vulvar region of a 44-year-old woman. A case like this confronts the
      gynecologists with the necessity of including a rare disease into particular
      consideration and investigation.

PMID- 7810249
TI  - [GEC-ESTRO Annual Brachytherapy Meeting, Linz 9-11 May 1994].

PMID- 7810250
TI  - [Neurosurgery in Austria--origin and continued development].

PMID- 7810251
TI  - "Ultrahigh" dexamethasone in acute brain injury. Results from a prospective
      randomized double-blind multicenter trial (GUDHIS). German Ultrahigh
      Dexamethasone Head Injury Study Group.
AB  - In a prospective randomized double-blind multicenter trial, the efficacy and
      safety of a 51-hour ultra-high intravenous dexamethasone dosing regimen was
      investigated in patients with moderate and severe head injury. 300 patients
      between 15 and 55 years of age were randomized to receive either placebo or
      dexamethasone: 500 mg intravenous infusion within 3 h after trauma initially,
      followed by 200 mg after 3 h, thereafter 8 times 200 mg at 6 hourly intervals,
      resulting in a total administered dose of 2,3 g in 51 hours. Primary end points
      for assessment of efficacy were: Modified Glasgow Coma Scale (grading 3-16) on
      Day 5, modified Glasgow Outcome Scale (grading 1-6) 10-14 months after injury,
      and the time interval until consciousness improved above a level of modified GCS
      > or = 8. Secondary endpoints were CT results and neurological and laboratory
      data. The two groups were well matched with respect to important prognostic
      variables, such as age, severity of trauma, and interval between trauma and
      application of the drug. 269 patients (89.7%) were available for final
      examination after 10-14 months. Results were surprisingly favourable in both
      groups: Lethality in the dexamethasone and placebo group was 14.3 and 15.4%,
      respectively, and 61.7 and 57.4%, respectively, achieved social and professional
      rehabilitation after 10-14 months (outcome scale 6). No statistical difference
      was seen between the dexamethasone and the placebo group in any of the primary
      end points of efficacy and safety (incidence of upper gastrointestinal bleeding,
      infection, and thrombosis).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7810252
TI  - [Predictors of treatment success after microsurgical operation of lumbar
      intervertebral disk displacement].
AB  - As far as medical decision making is based on weighing up individual risks and
      chances of a certain patient receiving a certain treatment, some knowledge is
      required about signs and symptoms which are associated with a certain outcome:
      they are called risk factors, or predictive factors. In lumbar intervertebral
      disc surgery, the most frequent undesired effect of the treatment is
      unsuccessfulness. Reviewing the literature about risk factors for
      unsuccessfulness, one recognizes a lot of unconfirmed or even contradictory
      findings. This inconsistency can possibly be attributed to the common use of a
      very simplified, unidimensional definition of the target variable "success of
      treatment". That is why we performed a prospective observational trial on 109
      patients in whom the success of lumbar intervertebral disc microsurgery was
      assessed after half a year using six different target variables. The rate of
      treatment success varied considerably, from 44% (when "return to previous
      occupation" served as the target variable) to 91% (with regard to "subjective
      contentedness"). Further target variables were intensity of sciatica, intensity
      of low back pain, activities of daily living, and postoperative paresis, giving
      intermediate success rates. We were able to identify some risk factors (for
      instance, duration of sick leave and of the recent pain episode, preoperative
      paresis, intensity of psychosomatic complaints), each of them being relevant to
      some of the target variables, but none of them associated with all of the target
      variables. We conclude that the multidimensional rating of treatment successes
      seems to promote risk research in multidimensional diseases.

PMID- 7810253
TI  - [Postoperative spondylodiscitis as the cause of failed-back syndrome--clinical
      aspects, diagnosis, therapy].
AB  - Postoperative lumbar spondylodiscitis can cause a failed back syndrome. With 0.1
      to 3% according to the literature it belongs to the rarer complications following
      lumbar disc surgery. We present the characteristic clinical picture and typical
      findings (ESR, plain X-rays, MR) with suspected spondylodiscitis on 19 patients
      (= 0.2% of 9492 operative interventions for lumbar disc prolapse from 1980 to
      1990) and show MR tomography to be the most sensitive investigation. Principles
      of therapy consist of lumbar immobilisation with a light cast orthesis for an
      average of 12 weeks and additional antibiotic therapy up to two weeks beyond
      normalisation of ESR. Finally results of therapy are presented with a satisfying
      outcome in 84.2% of cases.

PMID- 7810254
TI  - Corticotropin-releasing hormone enables weaning from ventilator in a
      neurosurgical patient under long-term controlled mechanical respiratory support.
AB  - A patient with recurrent hemorrhage into the posterior fossa leading to loss of
      central respiratory drive is described. Repeated i.v. application of
      corticotropin-releasing hormone over a period of 24 days enabled weaning from
      long-term controlled mechanical ventilation by reinstitution and maintenance of
      spontaneous respiration.

PMID- 7810256
TI  - Extradural hematoma complicating arachnoid cyst--case report.
AB  - A 37-year-old man is reported with post-traumatic extradural hematoma
      complicating an arachnoid cyst in the middle cranial fossa. While subdural and
      intracystic hemorrhages are well-known complications from this malformation, the
      association with extradural hematoma has only been reported in three cases in the
      literature. We describe a case occurring after head injury and discuss the
      etiology and treatment.

PMID- 7810257
TI  - [The relationship between lipid peroxidation and life span in Drosophila
      melanogaster].
AB  - Using Drosophila lines pre-selected for adaptive characters, studies have been
      made on the relationship between the intensity of lipid peroxidation and life
      span in flies of different genotype, age and physiological condition. It was
      shown that the intensity of lipid peroxidation depends mainly on different
      factors (sex, age, virginity) in different lines. No expected negative
      correlation was found between the level of lipid peroxidation and life span in
      hybrids between two inbred lines. The intensity of lipid peroxidation was
      inherited like a dominant character, the dynamics of aging--like a codominant one
      in females and superdominant in males. Both the level of lipid peroxidation and
      life span appeared to be sex-dependent characters.

PMID- 7810255
TI  - Severe lumbar stenosis caused by chronic spinal epidural hematoma and multiple
      disk disease--case report and review of the literature.
AB  - We present a patient whose radicular syndrome resulted from combined compression
      by disk herniation and lumbar chronic spinal epidural hematoma (CSEH). The lesion
      was extensively studied by CT and MRI and the preoperative diagnosis confirmed by
      microscopic examination. CSEH is a rare entity, typical of elderly and invariably
      involving the lumbar canal: only 11 similar cases have been reported up to date.
      We propose that an undefined number of CSEH remains clinically silent, hidden in
      the roomy lumbar canal, displacing but not injuring the roots of the cauda. The
      routine use of Gd-DTPA MRI, even in emergency, will significantly decrease
      mistakes localization and will provide the correct differential diagnosis.

PMID- 7810258
TI  - [Gas-exchange intensity in Daphnia in water polluted by different copper salts].
AB  - Studies have been made on the survival rate and oxygen consumption in Daphnia
      kept in solutions of four copper salts. The significance of anionic groups in
      total toxicity of the salts was demonstrated. Mechanisms of their action are
      discussed.

PMID- 7810259
TI  - [The characteristics of melatonin biosynthesis in the epiphysis of relatively
      wild and domesticated silver foxes Vulpes fulvus].
AB  - In earlier experiments, it had been demonstrated that at night melatonin
      concentration in the pineals of foxes Vulpes fulvus which were subjected to a
      prolonged selection for domestic behaviour, was higher than in undomesticated
      ones. A more detailed study of melatonin biosynthesis showed that concentration
      of melatonin precursor, namely serotonin, as well as the activity of N
      acetyltransferase and hydroxyindole-O-methyltransferase participating in
      melatonin synthesis, together with the content of dopamine and noradrenaline
      which regulate this process, are practically identical in the pineal gland of
      both groups of animals. Possible causes of differences in melatonin concentration
      in the pineal tissue of domesticated and undomesticated foxes are discussed.

PMID- 7810260
TI  - [A comparative study of the osmoregulating system in the hamsters Phodopus
      roborovskii and Phodopus sungorus].
AB  - The hamster Phodopus roborovskii is adapted to live in desert, Phodopus sungorus
      in less arid regions. Hamsters of both species have rather close values of blood
      serum osmolality and ion concentration, after dehydration the value of urine
      osmolality is found to be equally high. The microdissection of the kidney did not
      reveal any difference in the structure and arrangement of nephrons in cortex and
      medulla. According to the results of immunocytochemical analysis of the
      hypothalamo-hypophyseal neurosecretory system of hamster Phodopus roborovskii,
      compared to Phodopus sungorus, has a smaller quantity of vasopressin-positive
      neurons, which is likely to be a result of a release of larger quantities of
      vasopressin in long-term dehydration. It is suggested that of importance in the
      animal adaptation to life in arid condition may be not only morphofunctional
      reorganization of kidney but also of the hypothalamo-hypophyseal system which is
      involved in permanent secretion of vasopressin.

PMID- 7810261
TI  - [The comparative characteristics of the heart rhythm in cetaceans].
AB  - In Amazon River dolphins, bottle-nosed dolphins and white whales, comparative
      studies have been made on cardiac electrical activity using electrocardiographic
      and telemetric techniques. In all the species investigated, certain dependence of
      cardiac cycle duration on the phase of respiratory pause was observed. A
      pronounced bradycardia was noted in diving animals which reflects the level of
      their adaptation to hypoxia and hypoxemia. Autocorrelation functions of the
      dynamic sequences of cardiac intervals were calculated. The presence of "slow"
      waves in cardiac cycle was shown which were considerably increased during diving.

PMID- 7810262
TI  - [The reaction of the neocortical structures in the seal Pusa sibirica to a
      prolonged stay under water].
AB  - Using light and electron microscopic techniques, structural and functional
      changes in the neurones and glia of the Baikal seal neocortex were revealed
      during diving. These changes include shifts in tinctorial properties of cells, in
      the number of dendritic spines, cell ultrastructure (condensation and
      redistribution of nuclear chromatin, swelling of organoids, etc.). These changes
      are both non-specific and reversible, indicating high reserve capacities of the
      brain in this species.

PMID- 7810263
TI  - [The effect of excess catecholamines on grooming in rats in postnatal ontogeny].
AB  - During the first month of postnatal life, studies have been made of the effect of
      L-DOPA on grooming in rat puppies. It was found that within the first hour after
      injection of the drug, its inhibitory effect increases in the course of
      ontogenetic development. In some of the animals, the increase in grooming was
      observed, whereas in other ones the effect was absent. Inhibition concerns both
      the number of grooming outbursts and the duration of rhythmic phase. These
      changes are associated with the decrease of afferent input to the central nervous
      system and with inhibition of the activity of pacemakers of rhythmic motor
      excitation.

PMID- 7810265
TI  - [The interrelationship of the pre- and postsynaptic elements in neuromuscular
      endings with different functional profiles in the frog Rana temporaria].
AB  - Simultaneous investigation of nervous elements and acetylcholinesterase activity
      in nerve-muscle endings of m. iliofibularis of the frog Rana temporaria revealed
      different pattern of innervation of muscle fibres of various functional types.
      Myelinated axons of motoneurones of intermediate muscle fibres, in contrast to
      phasic ones, do not exhibit preterminal or nodal branching, forming the terminals
      with relatively rich ramification, but with poor spatial distribution which does
      not exhibit evident orientation along the muscle fibre. Neuronal axons of tonic
      motor system, in contrast to those of phasic and intermediate ones, do not have
      myelin sheath at the vicinity of the innervated muscle fibre; each synaptic zone
      of polysynaptically innervated tonic muscle fibres is supplied by a bundle of
      axons which form short synaptic contacts along their way; a peculiar feature of
      neuronal axons of the tonic motor system is that they expand beyond the
      innervated synaptic zone.

PMID- 7810264
TI  - [The effect of cadmium on the structure of the circadian cycle of waking-sleep
      and on the EEG in Wistar rats].
AB  - The effect of cadmium on spectral EEG parameters of the hippocampus,
      somatosensory, visual and auditory cortical zones, as well as representation of
      wakefulness, slow-wave sleep and paradoxical sleep has been studied in the
      diurnal cycle of Wistar rats. It was shown that single injections of cadmium
      chloride (3 mg/kg, intraperitoneally) induce significant changes in the structure
      of wakefulness-sleep cycle, whereas no reliable qualitative changes in EEG
      parameters were observed. After long-term (9 days) administration of cadmium
      chloride (1.5 mg/kg, intraperitoneally), epileptiform activity was noticed in the
      EEG pattern, whereas predisposition of animals to audiogenic seizures increased.

PMID- 7810266
TI  - [The neuromorphology of the olfactory pathways in mammals].

PMID- 7810267
TI  - [The structural-functional characteristics of the limbic nuclei in the anterior
      thalamus of mammals].

PMID- 7810268
TI  - [The importance of the Epstein-Barr virus and other viruses in the evolution of
      human host homeostatic systems].
AB  - There is a great number (150) DNA sequence homology with genes and mRNA of man.
      They are involved in expression of biological active matters, which are
      participate in homeostasis of host. This is an evidence of a long-time co
      evolution EBV and host-man populations. It play a great role in a vertical and
      horizontal dissemination some important for homeostasis genes of man.

PMID- 7810269
TI  - [Changes in the oxygen affinity of human and rabbit hemoglobin under the
      influence of blood plasma].

PMID- 7810270
TI  - Role of cytokines in inflammatory bowel disease.
AB  - The authors review the recent literature about the proinflammatory role of
      interleukins-1,-2,-6,-8, tumour necrosis factor and interferon-gamma in Crohn's
      disease and ulcerative colitis, as well as their possible use to assess disease
      activity and to design new therapeutic approaches. Most cytokines were secreted
      in excess in inflammatory bowel disease. An imbalance between interleukin-1 and
      interleukin-1 antagonist might be a factor responsible of the chronicity of
      intestinal lesions. Circulating levels of interleukin-2 receptor are related to
      disease activity. Preliminary data on the therapeutic use of antibodies to tumour
      necrosis factor are encouraging.

PMID- 7810271
TI  - Role of nitric oxide in gastrointestinal function and disease.
AB  - In the digestive tract, nitric oxide (NO) is extensively distributed, from the
      mouth to the anus, not only in mammals but also in lower vertebrates and even in
      invertebrates. It is involved in splanchnic and systemic hemodynamics, in mucosal
      protection, in immune mechanisms, in hepatic function, in endocrine secretion and
      in several other roles. It is also involved in the organization of the
      peristalsis as an inhibitory non-adrenergic non-cholinergic neurotransmitter and
      relaxant of the smooth musculature. The abundant literature dealing with NO in
      hepato-gastro-enterology is reviewed and discussed in a pragmatic approach for
      the gastroenterologist, with emphasis on the involvement of NO in pathophysiology
      and in the perspective of future therapeutics.

PMID- 7810273
TI  - Cytokines in alcoholic liver cirrhosis.
AB  - Interest for cytokines involvement in experimental and human liver injury has
      considerably increased over recent years. The present paper reviews the current
      knowledge in the field of alcoholic cirrhosis. The role of interleukin-1, tumor
      necrosis factor, interleukin-6, interleukin-8 and interleukin-10 are discussed
      together with their possible diagnostic and prognostic significance. Prospects
      for future investigations such as immunotherapy are underlined.

PMID- 7810272
TI  - [Chronic viral hepatitis and interferons: preliminary results in 60 patients with
      chronic hepatitis C and cellular mechanism of action].
AB  - Interferons exhibit antiviral and immunomodulatory properties. Antiviral effects
      appear mainly mediated via 2'5' oligoadenylate synthetase and protein kinase
      proteins which inhibit viral components synthesis. Interferons also influence the
      immune system through various mechanism among whom an increased expression of HLA
      class I antigens on hepatocyte plasma membrane and the promotion of natural
      killer cell activity leading to the clearance of infected hepatocytes. We report
      the results of various alpha interferon therapeutic regimens in 60 patients with
      chronic hepatitis C. In our series, 20 patients (33%) achieved a complete
      response but 78% of them relapsed after therapy withdrawal. Predictors of good
      response include young age, low serum ALT levels and mild liver injury. On the
      contrary, cirrhosis is associated with a poorer response.

PMID- 7810274
TI  - Interleukin-8 in alcoholic liver disease.
AB  - Acute alcoholic hepatitis is accompanied by features of the acute phase response,
      peripheral blood neutrophilia and liver neutrophil infiltrate even in the absence
      of demonstrable bacterial or fungal infection. Plasma levels of tumour necrosis
      factor (TNF) and interleukin-6 (IL-6), the major cytokine inducers of the acute
      phase response, are markedly raised in acute alcoholic hepatitis and correlate
      closely with clinical and laboratory indicators of disease severity. The potent
      neutrophil activator and chemotaxin interleukin-8 (IL-8) is released in response
      to TNF and recent interest has focussed on its possible role in producing the
      characteristic peripheral blood neutrophilia and liver neutrophil infiltrate in
      alcoholic hepatitis. Circulating IL-8 and liver tissue levels of IL-8 are
      markedly raised in alcoholic hepatitis, with highest levels in patients who die
      within the first four weeks of admission to hospital. There is a close
      correlation between hepatic IL-8 and infiltration with neutrophils. Less dramatic
      increases in circulating IL-8 are present in abstinent alcoholic cirrhotics and
      patients admitted for detoxification. These observations suggest a central role
      for IL-8 in the neutrophilia and hepatic neutrophil infiltrate characteristic of
      acute alcoholic hepatitis.

PMID- 7810275
TI  - Diminutive polyp: a rare presentation of breast cancer metastases to the colon.
AB  - Digestive metastases of breast cancer are well documented (1-4). We report a
      patient with metastatic breast cancer presenting as a 5 mm polypoid benign
      looking lesion. The diagnosis was confirmed by histopathology and immunostaining.

PMID- 7810276
TI  - Acute pancreatitis: a rare initial clinical manifestation of Henoch-Schonlein
      disease.

PMID- 7810277
TI  - Self-medication on a geriatric reactivation unit.

PMID- 7810279
TI  - The challenges of educational program evaluation.
AB  - The demand for fiscal restraint and accountability has forced health care
      facilities to carefully evaluate the benefits of new programs. Some time ago, the
      Long Term Care Nursing Department of Sunnybrook Health Science Centre in Toronto,
      Ontario, collaborated with Centennial College to provide a Gerontology
      Certificate Program to registered nurses. While originally conceived as a
      retention and recruitment strategy, it became obvious that such a program could
      and should have additional benefits to staff and long term care residents alike.
      This article describes the changes as indicated by three scales, and the benefits
      described by the registered nurses. It also illustrates, rather humorously, that
      even the more educated and experienced among us can make mistakes and learn from
      them!

PMID- 7810278
TI  - Nursing approaches to care of elderly persons with xerostomia (dry mouth).

PMID- 7810281
TI  - Needlesafe versus needleless intravenous injections.

PMID- 7810280
TI  - Breast self-examination is for women of all ages.

PMID- 7810282
TI  - Analysis of four major congressional committees' healthcare reform bills.

PMID- 7810283
TI  - When is a supervisor not a supervisor?

PMID- 7810284
TI  - Application of decision-making principles to the hiring process.

PMID- 7810285
TI  - The effects of azidothymidine therapy on pseudocholinesterase concentrations in
      asymptomatic HIV-positive patients.
AB  - The purpose of this study was to determine if a correlation exists between long
      term azidothymidine (AZT) therapy and low pseudocholinesterase concentrations in
      patients who are infected with the human immunodeficiency virus (HIV). A pilot
      study was conducted of 10 patients infected with HIV, 5 of whom were receiving
      AZT. Laboratory tests, including complete blood count (CBC), liver function
      tests, helper/inducer T lymphocyte numbers (CD4), serum dibucaine numbers, and
      serum pseudocholinesterase concentrations were examined. Control and study
      subjects both exhibited normal dibucaine numbers, but the pseudocholinesterase
      concentrations were significantly lower in the group that was not receiving AZT
      relative to the AZT treatment group. However, only two patients, neither of whom
      were receiving AZT, demonstrated low or borderline low pseudocholinesterase
      concentrations according to laboratory criteria. It is possible that
      pseudocholinesterase synthesis is significantly inhibited by the HIV disease
      process and that treatment with AZT partly reverses the inhibition. Associated
      variables contributing to low pseudocholinesterase concentrations in the HIV
      positive patient are explored.

PMID- 7810286
TI  - Fire safety in the operating room.
AB  - The operating room environment is considered a potentially significant fire
      hazard. The role of the anesthetist in preventing and handling fires is pivotal
      to patient survival. Means of preventing fires as well as extinguishing them are
      discussed.

PMID- 7810287
TI  - Cockayne syndrome: a case report.
AB  - A 4-year-old female with Cockayne syndrome presented for cataract extraction
      under general anesthesia. She was thin and frail; her neck, epiglottis and larynx
      were stiff; she was deaf and blind; and she could not speak, sit unaided, or
      perspire. At the time of her admission, she weighed 5.5 kg. Cockayne syndrome is
      a disease of childhood characterized by mental retardation and premature aging.
      Although the underlying abnormality appears to be autosomal recessive inheritance
      or metabolic (possibly thymic) dysfunction, there is no consensus on etiology.
      The multiple organ involvement carries significant implications for the
      anesthetist. Intubation can be technically difficult, and care of the skin can be
      problematic. Essential hypertension, hepatic deficiencies, osteoporosis,
      deafness, blindness, and other effects of premature aging may be encountered
      making perioperative management a challenge.

PMID- 7810288
TI  - AANA journal course: update for nurse anesthetists--treatment of avulsed teeth in
      the operating room.
AB  - Teeth that are avulsed in the operating room either during intubation,
      extubation, or other orally related procedures must be treated immediately in
      order to provide the best opportunity for success following replantation. New
      treatment methods have been developed that can significantly increase the success
      of replanted avulsed teeth. These methods utilize special pH balanced
      reconstituting fluids, cushioning devices, topical fluorides, and antibiotics
      that permit the storage of avulsed teeth for up to 96 hours with good success
      following replantation. This Journal course reviews the biologic background for
      these procedures and makes specific treatment recommendations.

PMID- 7810289
TI  - Motor neuron disease with multi-system involvement presenting as tetraparesis,
      ophthalmoplegia and sensori-autonomic dysfunction.
AB  - We carried out a postmortem examination on two Japanese patients, 64- and 80-year
      old men whose survival was prolonged with an artificial respirator. They had no
      family history of neuropsychiatric disorders and were suspected, clinically, as
      having a motor neuron disease that differed from amyotrophic lateral sclerosis
      (ALS). As well as upper and lower motor neuron impairment, they showed a variety
      of symptoms, such as sensory disturbances, hypohidrosis, impotence,
      ophthalmoparesis and/or atonic neurogenic bladder, and their protein content in
      cerebrospinal fluid was elevated markedly. Pathological examination revealed the
      following extensive nervous system involvement: (1) the upper and lower voluntary
      motor systems, including the IIIrd, IVth and VIth cranial nerve nuclei: (2) the
      reticular formation and its major afferent pathways; (3) the vestibulospinal and
      tectospinal systems; (4) the spinocerebellar system and the exteroceptive somatic
      afferent pathways; (5) the dentatorubral and pallidoluysian systems; and (6) the
      substantia nigra, locus ceruleus and intermediolateral and Onufrowicz's nuclei.
      Neither Bunina bodies, Lewy body-like hyaline inclusions nor ubiquitin
      immunoreactive skein-like structures were observed. The distribution of the
      lesions was quite different from that in patients with ALS and the other known
      related diseases. Recently, seven autopsied cases with clinical and
      histopathological similarities to our patients have been reported in Japan. Our
      conclusion is that our two and these seven patients should be classified as
      having a new motor neuron disease entity, which can be is differentiated from
      ALS.

PMID- 7810290
TI  - Presence of non-fibrillar amyloid beta protein in skin biopsies of Alzheimer's
      disease (AD), Down's syndrome and non-AD normal persons.
AB  - A total of 66 skin biopsies from persons with Alzheimer's disease (AD) or Down's
      syndrome (DS) and from persons without AD were used in this study. The age range
      was from 7 to 89 years. Positive immunoreactivity of skin biopsies to monoclonal
      antibody 4G8, which is reactive to amino acid residue 17-24 of synthetic amyloid
      beta protein (A beta), and 4G8-Fab (the antigen-binding fragment of 4G8 IgG,
      reactive only to amyloid plaque) was observed in the epidermis-dermis junction or
      the basement membrane of the epidermis and in some blood vessels of the biopsy
      skins of 13/18 (72%) AD, 9/10 (90%) DS, and 14/38 (37%) non-AD control cases. The
      Fisher exact probability test revealed a significant difference (P = 0.0415 one
      tailed) in immunoreactivity between AD and age-matched controls. There was also a
      significant difference (P = 0.0152 one-tailed; P = 0.0200 two-tailed) between DS
      and age-matched control in the same test. Immuno-gold electron microscopy
      examination of these cases with positive immunoreactivity revealed that the gold
      particles were deposited along the basement membrane of the epidermis. Amyloid
      fibrils were not observed in the regions with gold particles. Results of this
      study suggest that A beta is associated with the basement membrane of skin and is
      present in amorphous, non-fibrillar form as soluble A beta.

PMID- 7810291
TI  - Apoptosis related antigen, Le(Y) and nick-end labeling are positive in spinal
      motor neurons in amyotrophic lateral sclerosis.
AB  - Expression of Le(Y), a difucosylated type 2 chain determinant, has been
      previously identified as a characteristic of cells undergoing apoptosis.
      Immunohistochemistry using an antibody for Le(Y), as well as nick-end labeling
      for the detection of DNA breaks, was done on cervical spinal cord sections from
      ten patients with amyotrophic lateral sclerosis (ALS) and nine patients who had
      died from other causes. Le(Y)-positive immunoreactivity was seen in the motor
      neurons of seven ALS cases, but in none of the other cases. Nick-end labeling was
      also positive in four ALS cases. Double staining of motor neurons by anti-Le(Y)
      antibody and nick-end labeling was shown in these cases. Other Le(Y)-positive
      structures, such as reactive astrocytes and fat-laden microglia/macrophages in
      the lateral and anterior columns, were negative for nick-end labeling. These
      results suggest that the mechanism of cell death in the spinal motor neurons of
      ALS may be apoptosis.

PMID- 7810292
TI  - Hippocampal sclerosis: a common pathological feature of dementia in very old (>
      or = 80 years of age) humans.
AB  - In a neuropathological study of 81 brains of prospectively studied subjects of 80
      years of age or older at the time of death, 13 cases (16%), including 4 men and 9
      women, had hippocampal sclerosis (HpScl) affecting the vulnerable region of the
      hippocampus. In demented subjects of 80 years of age or older, the frequency of
      HpScl was even higher, 26%. Cases with HpScl had significantly fewer hippocampal
      senile plaques (SP) and neurofibrillary tangles (NFT) and parahippocampal NFT
      than cases without HpScl, but did not differ significantly in any of the other
      measured pathological parameters. Enzyme-linked analysis of synaptic protein
      immunoreactivity in a subset of 33 cases demonstrated significant decreases in
      the hippocampus, but not in frontal, temporal, parietal or parahippocampal
      cortices. All but 1 of the cases with HpScl had Blessed information, memory and
      concentration scores (BIMC) of 8 or more, and all were considered to be demented.
      In some patients memory disturbance was disproportionate to deficits in other
      cognitive areas. All but 4 of the cases with HpScl had many non-neuritic, amyloid
      plaques in the neocortex meeting NIA criteria for Alzheimer's disease (AD);
      however, given the advanced age of the subjects, amyloid plaques were considered
      to represent age-related cerebral amyloid deposition ("pathological aging") in
      most cases. Only 3 cases had both many SP and NFT in multiple cortical regions
      consistent with AD. Another case had brain stem and cortical Lewy bodies
      consistent with diffuse Lewy body disease (DLBD). A few ballooned neurons were
      present in the limbic cortices in 3 cases, including one case of dementia with
      argyrophilic grains (DAG) in limbic and orbital frontal and temporal cortices.
      The 8 cases without AD, DLBD or DAG included 4 cases in which no other obvious
      cause of dementia was detected and 4 cases in which HpScl was accompanied by
      either multiple cerebral infarcts or leukoencephalopathy, or both, that could
      have contributed to dementia. Patients with HpScl had risk factors, clinical
      signs and post-mortem pathological findings of cardiovascular disease, but due to
      the high prevalence of these conditions in very old humans, no significant
      correlation with HpScl was detected. This study demonstrates that HpScl is a
      common post-mortem finding in demented, but not normal, elderly subjects. It may
      contribute to. or be a marker for, the increased risk of dementia in subjects
      with documented cardiovascular disease or a history of myocardial infarction.

PMID- 7810293
TI  - Synapse loss in anterior horn neurons in amyotrophic lateral sclerosis.
AB  - This report deals with an ultrastructural investigation of the synapses of
      anterior horn neurons in the lumbar spinal cords of five patients with
      amyotrophic lateral sclerosis (ALS) who had mild neuronal depletion. Specimens
      from five age-matched, neurologically normal individuals served as controls. In
      each instance, the autopsy was performed within 3 h after death. A statistically
      significant decrease in cell body area, number of synapses and total synaptic
      length was found in the normal-appearing neurons of the ALS patients. The
      alterations were more pronounced in neurons with central chromatolysis. However,
      despite an approximately 20% reduction in the number of synapses, the length of
      the active synaptic zone of the normal-appearing neurons in the ALS patients was
      not diminished. This observation may be accounted for by a plasticity to the loss
      of synapses which maintained the active zone of the remaining synapses to
      increase synaptic efficiency. It is suggested that when the plasticity of the
      active zone reaches its limit, the continuing loss of synapses may lead to
      functional impairment. The capacity of the active synaptic zone to respond to
      progressive denervation of the anterior horn neurons may preserve motor function
      or slow the development of motor deficits in the early stage of degeneration of
      the lower motor neurons.

PMID- 7810294
TI  - Axonal torpedoes in cerebellar Purkinje cells of two normal mouse strains during
      aging.
AB  - The present study systematically investigated the proportional evolution of
      Purkinje cell (PC) axonal swellings, also termed torpedoes, during aging of the
      two unrelated mouse strains B6CBA and C57BL/6J. Torpedoes were identified using
      monoclonal antibodies against the calcium-binding protein calbindin D-28k in mice
      ranging in age from 8 days postnatally up to 32 months. The relative density of
      PCs bearing torpedoes in animals up to 6 months of age was less than 0.1%. The
      number increases between 6-8 months and rises further in older mice almost
      linearly up to 13.7% affected PCs in the oldest animal (32 months) studied. In
      contrast, PC loss, as indicated by parvalbumin-immunoreactive empty baskets, is
      only at a very moderate level (less than 0.5%) in these strains. While the
      proximal axonic segments often show two and occasionally up to five swellings and
      frequently appear to be hypertrophied as a whole, the dendritic trees and
      neuronal somata of the affected PCs exhibit normal morphology. On rare occasions
      adaptive reactions indicated by "arciform axons" and enlarged varicosities of
      recurrent collaterals were observed. The results demonstrate that in addition to
      age-related PC loss of whatever degree, axonal disturbances of PCs, indicated by
      torpedoes, are present, leading most probably to a graded loss of cerebellar
      cortico-fungal projections.

PMID- 7810295
TI  - Cerebral and cerebellar gangliocytomas: a morphological study of nine cases.
AB  - Hypothalamic gangliocytomas have been shown to contain immunoreactivity for
      hypophysiotropic peptides and some have been associated with endocrine
      dysfunction. Extrahypothalamic gangliocytomas are usually not associated with
      endocrine abnormalities. We studied nine cerebral or cerebellar gangliocytomas
      from six men and three women; none of the patients had detectable alterations of
      endocrine homeostasis. On histological examination, the tumor cells resembled
      hypothalamic neurons. Electron microscopy disclosed the presence of dense-core
      vesicles in neuronal cytoplasm and processes resembling Herring bodies, and there
      were synaptic contacts between tumor cells. All but two tumors contained
      immunocytochemical positivity for at least one peptide hormone or amine; these
      included somatostatin, corticotropin-releasing hormone, beta-endorphin, galanin,
      vasoactive intestinal peptide, calcitonin, serotonin, catecholamines or met
      enkephalin. These tumors have been thought to represent neoplasms arising in
      ectopic autonomic neural tissue. Their morphological features, their similarity
      to hypothalamic gangliocytomas and the multiple immunoreactivities shown here
      suggest that they can be regarded as tumors of peptidergic neurons that are
      widely distributed throughout the central nervous system.

PMID- 7810297
TI  - Complete absence of the cerebellum: a report of two cases.
AB  - Complete absence of the cerebellum is an extremely rare malformation. Most
      previous cases have had some remnant of cerebellar cortex, however small. We
      report two infants with complete absence of the cerebellum. One infant had
      hydrocephalus and numerous other malformations. The other infant had
      micrencephaly, which has not previously been reported in association with an
      absent cerebellum.

PMID- 7810296
TI  - Initiation of satellite cell replication in bupivacaine-induced myonecrosis.
AB  - To determine how and when the satellite cells are stimulated to replicate in
      muscle regeneration, the rat soleus muscle was examined chronologically after
      bupivacaine-induced myonecrosis. Bromodeoxyuridine and desmin-positive
      mononuclear cells, indicating the start of satellite cell replication, were seen
      25 h after bupivacaine treatment when macrophages had already invaded the
      sarcoplasm of necrotic fiber. These findings suggest that muscle regeneration
      starts as early as the time at which macrophages begin to scavenge necrotic
      material. Proliferating myoblasts increased in number, reaching a maximum at 49 h
      after myonecrosis, and decreased in number 3 days after the myoblasts fused with
      each other form myotubes. The satellite cell proliferation after bupivacaine
      induced myonecrosis began at almost the same time as in crush injury, and earlier
      than after muscle transplantation using whole intact or minced muscle fragments.
      The earlier beginning and more rapid regenerating process probably resulted from
      the preservation of intact satellite cells, blood vessels and peripheral nerves
      in the bupivacaine-induced myonecrosis.

PMID- 7810298
TI  - Gerstmann-Straussler-Scheinker disease showing beta-protein type cerebellar and
      cerebral amyloid angiopathy.
AB  - Cerebral amyloid angiopathy is observed in several brain degenerative disorders,
      but this pathological condition has received little attention in Gerstmann
      Straussler-Scheinker disease (GSS). We report a 69-year-old man who showed the
      cardinal features of GSS together with typical and extensive congophilic
      angiopathy. Immunohistochemical studies revealed that the vast majority of the
      amyloid plaques present in the brain of this patient were consistently labeled by
      anti-prion protein (PrP) antibody. Double immunostaining disclosed many
      additional beta-protein immunoreactive plaque-like lesions, including a special
      type of "hybrid" plaque with colocalization of PrP and beta-protein (beta-PrP).
      The vascular amyloid deposits seen in both the cerebellum and cerebrum were
      immunoreactive only to anti-beta-protein antibody. It seems likely that the
      extensive deposition of beta-protein amyloid (including brain vascular
      amyloidosis) seen in this and other similar cases is part of pathology of GSS,
      although the possibility that this finding is due to ageing or concomitant
      Alzheimer's disease cannot be completely ruled out.

PMID- 7810299
TI  - Perineurial hemorrhage in ischemic nerve after anticoagulation.
AB  - We report a 29-year-old woman who developed severe left leg ischemia after aortic
      dissection and left common iliac artery occlusion. Light microscopic studies
      revealed severe nerve and muscle ischemic changes at the calf level. Nerves also
      showed extensive perineurial hemorrhage, most likely secondary to heparin
      administration. Perineurial hemorrhage should be considered as one of the
      possible complications of anticoagulant therapy.

PMID- 7810300
TI  - The long term outcome of secretory otitis media in children and the effects of
      surgical treatment: a ten year study.
AB  - Two hundred and twenty two children with bilateral secretory otitis media were
      allocated at random for adenoidectomy, adenotonsillectomy or for neither
      procedure. In all cases only a unilateral grommet was inserted. The contralateral
      unoperated ear was examined during a ten year period to show otoscopic clearance,
      change in tympanometric status and improvement in mean hearing threshold.
      Adenoidectomy or insertion of a grommet alone produces similar improvement but in
      combination are more effective than either procedure in isolation. The unoperated
      ear in cases not receiving either procedure reflects the natural history of the
      condition. It shows a steady improvement in all outcome measures as time passes.

PMID- 7810301
TI  - [Rupture of the round window. Differential diagnosis in sudden deafness and acute
      vestibular symptoms].
AB  - Rupture of the round window has to be considered in the differential diagnosis of
      sudden hearing loss with or without vertigo. The symptoms of this pathology vary
      a lot. No clinical examination with a sufficiently high selectivity and
      sensibility exists. The low therapeutical risk is stressed: exploratory and
      therapeutic tympanoscopy with grafting of the round and/or oval window.

PMID- 7810302
TI  - [Recurrent vertigo and basilar megadolicho-arteries].
AB  - Seven patients with basilar megadolicho-artery and predominant otovestibular
      symptoms are reported. Pathology of this entity, its signs and symptoms,
      diagnostic tools and treatment options are reviewed.

PMID- 7810303
TI  - Middle ear pressure balance under normal conditions. Specific role of the middle
      ear structure.
AB  - The mechanisms which govern under normal conditions the balance of middle ear
      pressure are discussed. The regular periodic active process of gas transfer
      through the Eustachian tube, the steady gas diffusion between middle ear and
      blood compartment and finally the pressure buffer role played by the mastoid are
      successively considered.

PMID- 7810304
TI  - The bone anchored hearing aid and auricular prosthesis.
AB  - The bone anchored hearing aid (B.A.H.A.) has been fitted to 10 of our patients
      presenting a bilateral profound conductive hearing loss and who were unable to
      wear a classical hearing aid. The group of patients with bilateral inoperable
      aural atresia (n = 5) formed the main indication and were found to give the best
      results. Cases with bilateral chronic otitis media (n = 5), presenting otorrhea
      each time a classical hearing aid was worn, formed the second indication.
      Audiometric performances are dependent on the bone conduction thresholds. The
      auricular epithesis has been adapted in 11 cases, mainly for atretic ears. The
      surgery for B.A.H.A. and epithesis is now routinely performed in one stage and
      has been found safe and reliable. The skin reactions around the abutments (total
      number fixtures = 32) were found to be rare and often easy to treat. Only around
      one abutment further subcutaneous tissue reduction was necessary to stabilize the
      skin. The B.A.H.A. and auricular epithesis are valuable alternatives in those
      cases where the limits of reconstructive (middle or outer ear) surgery are
      reached.

PMID- 7810305
TI  - [Hearing loss following lumbar puncture: case report and literature study].
AB  - This report describes a patient with permanent hearing loss after spinal
      anesthesia. The literature is reviewed, particularly concerning incidence and
      possible causes. The incidence is surprisingly high and related to the size of
      the needle. The role of the cochlear aqueduct as a transmitter of a decreased
      fluid pressure in the subarachnoid space to the perilymph of the labyrinth is
      discussed.

PMID- 7810306
TI  - Cortical electric response audiometry (slow vertex responses) in forensic
      audiology.
AB  - The interest of slow vertex response audiometry (cortical evoked response
      audiometry), mainly in the diagnosis of pseudohypacousis is reported. The
      procedure is of interest to forensic audiometry.

PMID- 7810307
TI  - [Psychosocial treatment of tinnitus].
AB  - After all medical and audiological treatments have failed, tinnitus patients
      often get the advise to "learn to live with it". The aim of psycho-social
      treatment is assisting patients in the identification of tinnitus aggravating
      factors and teaching them various coping skills. Treating these problems is
      primarily recommended for patients suffering from other disorders, even related
      to tinnitus. Motivation for psycho-social treatment depends on the ability of
      patients to accept tinnitus as a fundamental fact in their existence.

PMID- 7810308
TI  - Clear cell sarcoma of the pre-parotid region: an initial case report.
AB  - An unusual case of clear cell sarcoma (CCS) found in the parotid region of a 75
      year-old man with a long history of chronic lymphoid leukemia is reported.
      Treatment of the patient included a total parotidectomy with preservation of the
      facial nerve. The tumor was pathologically consistent with a clear cell sarcoma.
      Since CCS originates from the neural crest and is melanin producing, we suggest
      that this particular tumor originated from the superficial musculo-aponeurotic
      system (SMAS). To our knowledge, this is the first case of CCS that has been
      reported in the parotid region.

PMID- 7810309
TI  - Reconstructive aspects of malignant parotid surgery.
AB  - High grade malignant tumours of the parotid gland require radical resections. The
      surgeon is therefore confronted with the problem of a reliable and minimally
      deforming reconstruction. Due to different manifestations, locations and spread,
      one should be familiar with a variety of reconstructions. Four case histories are
      presented, illustrating the necessity of approaching each parotid tumour
      resection and the resulting defect individually. Technical aspects of different
      reconstructions are discussed.

PMID- 7810310
TI  - [Sinusitis in atopic children].
AB  - Allergy is one of the etiologic factors in the pathogenesis of sinusitis. In
      order to investigate the allergic influence on the incidence of sinusitis, a CT
      scan of the sinuses in 59 atopic children with nasal complaints of rhinosinusitis
      was performed. Sinusitis was found in 36 children (61%). These results were
      compared to a previous study of 196 mainly non-atopic children (atopy was no
      exclusion criteria). Identical inclusion and evaluation criteria were used.
      Sinusitis was found in 125 children (64%). According to these results it seems
      that the prevalence and the extent of sinusitis is not determined by the presence
      of allergy.

PMID- 7810311
TI  - Costs and effects of tracheoesophageal speech compared with esophageal speech in
      laryngectomy patients.
AB  - The hospital costs and the effects on speech are compared for tracheoesophageal
      (TE) speech and esophageal (E) speech in laryngectomy patients. TE-speech is more
      intelligible and the rehabilitation is faster (four versus nine months), but it
      is more expensive for the hospital. E-speech needs more speech rehabilitation
      sessions (average of 23,422 BF/patient) than TE-speech (7,157 BF). TE-speech
      involves primary (6,192 BF) or secondary placement (25,357 BF), replacement
      (average of 19,443 BF/patient/year) and in about ten percent closure of the
      fistula (39,135 BF/patient) and switching over to E-speech. On the basis of these
      data the expected average costs per patient can be calculated. These are
      definitely higher for the TE-speech than for E-speech.

PMID- 7810312
TI  - [ENT aspects of leprosy. Observations on the physiopathology].
AB  - Beginning leprosy detected by careful ENT examination is described. Transmission
      by nasal droplets appears to be the most plausible theory. Spread of infection
      from the nose to the facial nerve through the vidian nerve is a personal
      hypothesis.

PMID- 7810313
TI  - [Nosocomial infections in otolaryngological surgery].

PMID- 7810314
TI  - [Basic elements of antibiotic prophylaxis: the rationale].
AB  - In brief, the following study shows the necessity of chemoantibioticprophylaxis.
      This is to be carried out in operations where the risk of contamination is
      probable. The antibiotic is to be administered before the operation. Active drugs
      are used to confront foreseen pathogenics and ensure sufficient M.I.C. for the
      duration of the operation itself. Moreover, the results obtained from a
      polycentric research are underlined. The results show post-operative infections,
      with particular importance being placed on the antibiotics to be used as far as
      isolated germs are concerned.

PMID- 7810315
TI  - [Pharmacological economy: economic aspects and management of antibiotic therapy].

PMID- 7810316
TI  - [Antibiotic prophylaxis in otological and otoneurological surgery].

PMID- 7810317
TI  - [Antibiotic prophylaxis in oncological pharyngolaryngeal surgery].

PMID- 7810318
TI  - [Antibiotic prophylaxis in the surgery of the nose and paranasal sinuses].

PMID- 7810319
TI  - [Antibiotic prophylaxis in nasal surgery: clinical-experimental contribution].

PMID- 7810320
TI  - [Medical and legal aspects of antibiotic prophylaxis in otorhinolaryngeal
      surgery].

PMID- 7810321
TI  - [Antibiotic prophylaxis in otolaryngological surgery: results of a multi-center
      study].

PMID- 7810322
TI  - [Otorhinolaryngological manifestations of lymphomas: discussion].

PMID- 7810323
TI  - [Influence of a CNS pathology on the electrocochleography response].
AB  - This study analyzed 73 electrocochleographic recordings made in children with a
      normal hearing threshold, selected retrospectively from 1563 recordings made
      between 1973 and 1990. The aim of the study was to check the original findings
      for any correlation between the various response parameters which might be
      indicative of a pathological condition. Compound action potential (AP) latency
      and amplitude, presynaptic summation potential (SP) and cochlear microphonic (CM)
      amplitudes and AP rapid adaptation behavior were calculated and recordings were
      associated with clinical information on aetiologic diagnosis, otoscopic
      examination, impedance measurement data and the finding of any central nervous
      system (CNS) pathology. The trend of the amplitudes as a function of the
      intensity of all three potentials (input-output functions), CM and SP in
      particular, demonstrated unexpected scattered values especially towards the high
      intensities. This was found correlated to the presence of CNS pathology. The
      comparison between the two groups (with vs without CNS pathology) with the aid of
      the Student's t-test proved statically significant, especially for CM and SP
      amplitudes while rather less so for AP amplitude. In particular, all CM and SP
      amplitude values outside the confidence intervals (calculated as 95% of normal
      cases) revealed CNS pathology. It has been suggested that the influence of the
      CNS on cochlear function is due to a disturbed function of the olicocochlear
      bundle, which is known to have an inhibitory effect on cochlear dynamics;
      furthermore, there is also proof that it can be activated regardless of any ipso
      and/or contra-lateral acoustic stimulation. The effects observed on the
      electrocochleography in cases with CNS disorders would thus be explained by an
      interruption of the olivocochlear bundle at the CNS level or a disruption of the
      CNS mechanism capable of controlling its activation.

PMID- 7810324
TI  - [Vocal function after cordectomy (traditional surgical treatment vs CO2 laser): a
      comparative objective-instrumental evaluation].
AB  - Concerning the wider use of the CO2 laser in the treatment of laryngeal diseases,
      the Authors, in a comparative study based on an objective-instrumental
      evaluation, evaluated residual vocal function after traditional surgical
      treatment (chordectomy) vs. CO2 laser treatment. Forty-one patients treated for
      T1a glottic carcinoma (U.I.C.C. 1987) in last 8 years were examined Vocal
      function following CO2 laser surgery was evaluated in 17 patients (16 males and 1
      female, aged between 38 and 78, with an average age of 53) and compared to vocal
      function of 24 patients treated with traditional chordectomy (23 males and 1
      female, aged between 51 and 73, with an average age of 58). All patients showed a
      minimum follow-up of 30 months and none, at the time of evaluation, had undergone
      phonatory re-education. Glottic functionality evaluation was performed as
      follows: Evaluation of anatomical and functional results by means of a rigid
      fiberoptic laryngoscopy and subsequent photographic documentation for successive
      comparative evaluation. Evaluation of residual voice quality by phoniatricians
      otorhinolaryngologists and the patients themselves. Recording and electroacoustic
      analysis of some vocal samples. Laryngeal objectivity of surgical results were
      constantly related to subjective and instrumental voice evaluation. Phonatory
      results in patients treated with CO2 laser were better than those found in
      patients treated with traditional chordectomy.

PMID- 7810325
TI  - [Evolution of medical education. Part I].

PMID- 7810326
TI  - [Taste disorders in forensic medicine].
AB  - Taste disorders can a rise from lesions of peripheral receptors, taste control
      pathways or cortical area involvement. Among peripheral lesions, trauma of the
      tongue and oropharynx are the most common. Iatrogenic lesions of facial and
      glossopharingeal nerves are very important in Forensic Medicine, while there are
      different opinions about taste alterations due to head injuries; hypogeusia
      associated to smell disorders are found in 0.4-0.5% of patient after head trauma
      with good prognosis (90% healing) while qualitative disorders are more common
      (30%). The Authors describe clinical methodologies for taste evaluation and their
      application in Forensic Medicine. Forensic estimation of taste disorders con be
      classified by two main groups: study of cause relation between the occurrence and
      damage and quantitative valuation of the damage in three different juridical
      ambits: Penal, Civil, Insurance and foresight. In Penal Right taste damages could
      be classified among personal lesion crimes and can be classified as serious
      (permanent injury of taste) ore very serious (complete lost of taste function).
      Italian Legislation equipare the 5 sense organs. In Civil Right evaluation the so
      called "biologic damage" and working ability are considered; this means very
      different evaluations. In the most recent baremes, generic damage is estimated by
      different Authors from 0 to 10% while with regard to specific working capacity,
      common evaluation criteria does not exist. In Insurance taste disorders
      evaluation is based only on working ability and not on biologic damage. In the
      previdenzial ambit, taste disorders are not even included in the most recent
      tables of permanent invalidity estimation. The Authors propose new and more
      efficacious valutation criteria for taste disorders in all ambits, hoping for
      more interest in the Forensic aspects of taste, a too often forgotten sensory
      function.

PMID- 7810327
TI  - Chromogranin A: a multipurpose prohormone?

PMID- 7810328
TI  - Endothelium-dependent relaxation resistant to N omega-nitro-L-arginine in the rat
      hepatic artery and aorta.
AB  - Nitric oxide (NO)-independent pathways contributing to acetylcholine (ACh)
      induced relaxation were examined in the rat isolated hepatic artery and aorta at
      low and high levels of precontraction induced by phenylephrine (PhE). In the
      hepatic artery, the ACh-induced relaxation was unaffected by the NO synthase
      inhibitors N omega-nitro-L-arginine (L-NOARG, 0.3 mM) and N omega-nitro-L
      arginine methyl ester (0.1 mM) at either level of pre-contraction. In the aorta,
      L-NOARG virtually abolished the ACh-induced relaxation at a high level, but only
      partially reduced the response at a low level of precontraction. Methylene blue
      (10 microM) and indomethacin (10 microM) did not affect the ACh-induced
      relaxation in the hepatic artery. L-NOARG completely inhibited the cGMP and cAMP
      increases induced by ACh in both types of artery. In the presence of L-NOARG, ACh
      was unable to relax the hepatic artery precontracted by K+. The sensitivity to
      PhE was increased less by L-NOARG (threefold) than after endothelial denudation
      (tenfold) in the hepatic artery, whereas no such difference was observed in the
      aorta. The relaxation induced by the NO donor 3-morpholino-sydnonimin did not
      differ between the arteries after endothelial denudation. These results are
      compatible with the existence of an endothelium-dependent inhibitory pathway
      distinct from the NO and cyclooxygenase pathways. This pathway seems to
      contribute more to the ACh-induced relaxation in the hepatic artery than in the
      aorta, whereas the opposite appears to be true for the NO pathway.

PMID- 7810329
TI  - Vasoinhibitory activity of synthetic peptides from the amino terminus of
      chromogranin A.
AB  - Naturally occurring amino terminal fragments of chromogranin A (CGA), the calcium
      binding protein found in all endocrine secretory vesicles, have vasoinhibitory
      activity when tested in isolated segments of the endothelium-denuded human
      saphenous vein. Synthetic peptides corresponding to sequences within the first 76
      residues of chromogranin A have been made and tested for biological activity.
      Full length vasostatin I (CGA1-76) (40 nM), but not the truncated vasostatin I,
      CGA1-40 (100 nM) mimics natural chromogranin A fragments in its inhibition of
      contractions induced by endothelin-1 (ET-1) in calcium containing medium. CGA1-40
      (100 nM) mimics the inhibitory effect of the vasostatins on the contractions
      induced in the absence of extracellular calcium by high potassium and
      noradrenaline, but not by ET-1. The iodinated peptides both exhibit saturable
      binding in an aortic smooth muscle cell line, indicative of a single class of
      high affinity binding protein ('receptor' with an apparent KD of approximately 45
      nM. This binding is not affected by endothelin-1. Iodinated peptides can be
      crosslinked to a single polypeptide in binding experiments performed on intact
      calf aortic smooth muscle cells.

PMID- 7810330
TI  - Spectral sensitivities of short- and long-wavelength sensitive cone mechanisms in
      the frog retina.
AB  - ERG mass photoreceptor responses were recorded across the isolated, aspartate
      perfused retina of the frog, Rana temporaria, in order to determine spectral
      sensitivities of cones. Cone responses were distinguished from rod responses by
      their faster kinetics, and responses from different cone types were isolated by
      selective background adaptation. Our main finding is that of a novel short
      wavelength sensitive cone population peaking at about 431 nm. Further, we find
      that the sensitivity spectrum of the dominant long-wavelength sensitive cone
      population fully accounts for the most common type of photopic ganglion cell
      spectrum. Both can be described by a nomogram with lambda max = 562 nm. This
      resolves a long-standing apparent conflict between cone absorbance spectra and
      ganglion cell sensitivities. Including the 502 nm cones previously described by
      microspectrophotometry, the frog possesses a collection of cones that could
      support trichromatic photopic vision.

PMID- 7810331
TI  - Increased lymphatic hyaluronan output and preserved hyaluronan content of the rat
      small intestine in prolonged hypoproteinaemia.
AB  - Nephrotic syndrome was induced in seven rats by daily aminonucleoside injections.
      Experiments were performed in anaesthesia 6 or 7 d later when protein loss in
      urine had reduced serum colloid osmotic pressure (COP) to 8.2 +/- 0.9 (SD) mmHg
      compared with 20.2 +/- 2.2 mmHg in controls (P < 0.01). Due to the decreased COP
      in the nephrotic rats, lymph flow in the main mesenteric lymphatic was 29.5 +/-
      11.5 microliters min-1 compared with 4.2 +/- 2.2 microliters min-1 in the control
      rats (P < 0.01). The corresponding hyaluronan concentrations were 3.4 +/- 0.9
      micrograms ml-1 and 12.0 +/- 3.5 micrograms ml-1, respectively (P < 0.01).
      Nevertheless lymphatic hyaluronan output was doubled in the nephrotic rats, but
      this did not affect the hyaluronan content of the small intestine of 192 +/- 58
      micrograms g-1 dry wt compared with 215 +/- 69 micrograms g-1 in controls (P >
      0.05). During a 20 min intravenous 0.9% saline infusion of 4 ml 100 g-1 rat, the
      hyaluronan concentration increased to 18.3 (6.0) micrograms ml-1 in mesenteric
      lymph in controls, whereas the concentration in lymph from the nephrotic rats
      remained unchanged. Lymphatic output increased, however, in this group as well
      due to the elevated flow. The amount of hyaluronan cleared daily by the main
      mesenteric lymphatic in awake rats corresponds to about half the tissue
      hyaluronan content in the drained area (ostgaard & Reed 1993 b).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7810332
TI  - Electrophoretic analysis of cat parotid saliva in response to parasympathetic
      stimulation or infusion of bethanechol.
AB  - The protein constituents of cat parotid saliva evoked by parasympathetic
      stimulation or the infusion of bethanechol have been compared by sodium dodecyl
      sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). The SDS-PAGE patterns
      were highly reproducible for an individual cat and revealed up to 30 polypeptide
      bands in microlitre volumes of unconcentrated saliva. Only minor and
      predominantly quantitative differences were detected in the salivary protein
      composition of different cats. SDS-PAGE demonstrates quantitative rather than
      qualitative changes in the protein composition of saliva evoked in response to
      different stimuli. The latter included preliminary observations on the effect of
      vasoactive intestinal peptide (VIP) on the bethanechol-evoked response.

PMID- 7810334
TI  - Electromyographic responses of the human triceps surae and force tremor during
      sustained submaximal isometric plantar flexion.
AB  - The objective was to investigate electromyographic activity (EMG) and isometric
      force tremor (IFT) changes during a sustained sub-maximal isometric contraction
      in two muscles acting upon the same joint but differing in muscle fibre
      composition. Surface and intra-muscular EMG activity from the gastrocnemius and
      soleus muscles and IFT were recorded during an exhausting isometric plantar
      flexion (30% of maximal voluntary contraction). Surface EMG amplitude (RMS) of
      both gastrocnemius and soleus muscles increased significantly over time.
      Gastrocnemius EMG RMS increased in a non-linear fashion while soleus EMG RMS
      increased linearly. A significant linear decrease of surface EMG mean power
      frequency (MPF) was observed over time for both muscles. The decrease in
      gastrocnemius MPF was significantly greater than that for soleus. Intra-muscular
      EMG results showed similar trends. Correlations of intramuscular EMG RMS and MPF
      with time were, however, characterized by lower correlation coefficients than
      those from the surface EMG. Isometric force tremor RMS significantly increased
      non-linearly with duration of contraction, while IFT MPF showed a significant
      linear decrease with time. Changes in surface EMG RMS were correlated to changes
      seen in IFT RMS, in particular, for the predominantly fast twitch gastrocnemius
      muscle. Correlation coefficients of surface EMG MPF and IFT MPF were lower than
      RMS correlations. The associated changes in IFT and EMG with fatigue indicate
      alterations in motor unit firing rate, recruitment and synchronization. The
      muscle specificity of the EMG and IFT changes suggests a coupling to muscle fibre
      type composition, although differences in the relative force contribution of each
      muscle could also affect the results.

PMID- 7810333
TI  - Factors limiting force during slow, shortening actions of the quadriceps femoris
      muscle group in vivo.
AB  - Speed-torque relations of the quadriceps femors muscle group were determined
      using eight healthy subjects. Isometric or isovelocity, shortening muscle actions
      were performed at 15 speeds (0-6.28 rad s-1) and torque was measured 0.78 and
      0.52 rad below horizontal. Unilateral actions were evoked by surface electrical
      stimulation or by maximal voluntary effort. Stimulation current evoked a torque
      equal to approx. 70% of maximal voluntary isometric and was held constant across
      speeds. For the voluntary or stimulation tests, torque decreased (P < 0.05) with
      increasing speed. This response in relative terms was greater (P < 0.05) for the
      stimulation than for the voluntary tests. The difference in the decline in
      relative torque for the simulation vs. voluntary tests was not influenced by the
      angle at which torque was measured, and thereby muscle length. Speed-torque data
      for the two stimulation tests fit a linearized plot of a hyperbolic relation for
      the higher tests speeds. When torque was measured at the greater joint angle
      (0.78 rad), and thereby longer muscle length, the equation was Po-P/V = Po 0.724
      1.078 (P < 0.05, r2 = 0.95) for speeds greater than 0.70 rad s-1. For the shorter
      muscle length, the equation for data collected at speeds greater than 1.13 rad s
      1 was Po-P/V = Po 0.467 + 4.61 (P < 0.05, r2 = 0.91). Inclusion of data for the
      next slower speed markedly compromised the 'fit' for either linear
      relation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7810336
TI  - Effects of glyceryl trinitrate, nitroprusside and nitric oxide on arterial,
      venous and capillary functions in cat skeletal muscle in vivo.
AB  - The aim of the present study was to analyse quantitatively, on a cat
      gastrocnemius preparation in vivo, the effects of i.a. or i.v. administered
      glyceryl trinitrate (GTN), sodium nitroprusside (SNP) or nitric oxide (NO
      dissolved in saline) on vascular resistance (tone) in the following consecutive
      vascular sections: Large-bore arterial resistance vessels (> 25 microns), small
      arterioles (< 25 microns), and the veins. Effects on hydrostatic capillary
      pressure (Pc,v) and transcapillary fluid exchange were simultaneously recorded.
      Close-arterially infused GTN (1-4096 micrograms kg tissue-1 min-1), SNP (0.5-32
      micrograms kg tissue-1 min-1) and NO (0.14-0.82 mg kg tissue-1 min-1) elicited a
      generalized dose-dependent dilator response in all three sections, though with a
      preferential action on the arterial side. Further, these agents caused an
      increase in Pc,v and transcapillary fluid filtration. The sites of action along
      the vascular bed of these exogenous vasodilators differed from that previously
      established for endogenous EDNO. Infusion of GTN, SNP and NO during EDNO blockade
      (L-NAME) could, therefore, not restore the vascular resistance distribution to
      that prevailing in the initial control state. Myogenic vascular reactivity to
      standardized transmural pressure stimuli was clearly depressed by GTN and SNP.
      Intravenously infused GTN (4-512 micrograms kg body wt-1 min-1) and SNP (4-64
      micrograms kg body wt-1 min-1) decreased arterial pressure and elicited, via
      reflex sympathetic activation, a dose-dependent vasoconstriction in skeletal
      muscle, a decrease in Pc,v, and net transcapillary fluid absorption. The
      constrictor response thus overruled the direct dilator effect of the drugs. The
      plasma volume expansion known to result from long-term systematic administration
      of nitrovasodilators seems in part to be caused by transcapillary fluid
      absorption in skeletal muscle.

PMID- 7810335
TI  - Participation of prostaglandins and bradykinin in the effects of angiotensin II
      and converting enzyme-inhibition on sympathetic neurotransmission in vivo.
AB  - We investigated the mechanism(s) by which angiotensin converting enzyme (ACE)
      inhibition and angiotensin (Ang) II influence peripheral sympathetic
      neurotransmission in canine gracilis muscle in situ, with alpha-adrenoceptors
      either intact or irreversibly blocked by phenoxybenzamine. ACE-inhibition by
      ramiprilat reduced, and subsequent infusion of Ang II (30 ng kg-1 min-1 i.v.)
      markedly increased arterial plasma Ang-(1-8)octapeptide levels, basal muscle
      perfusion pressures and mean arterial pressure. Local intra-arterial bolus
      injection of Ang II caused marked vasoconstriction followed by vasodilation. This
      vasoconstrictor response was enhanced and the ensuing vasodilation was abolished
      following prostaglandin synthesis inhibition by diclofenac. The vasoconstrictor
      response to low frequency (0.5 Hz) sympathetic nerve stimulation was also
      enhanced by diclofenac. The nerve stimulation-evoked noradrenaline (NA) overflow
      was reduced by ramiprilat when alpha-adrenoceptors were blocked (-11 +/- 3%, P <
      0.05), but increased when alpha-adrenoceptors were intact (+28 +/- 14%, P <
      0.05). During ACE-inhibition, effective bradykinin receptor antagonism by HOE 140
      reduced stimulation-evoked NA overflow irrespective of alpha-adrenoceptor
      blockade (i.e. by 25 +/- 5 and 20 +/- 3% in the absence and presence of alpha
      adrenoceptor blockade, respectively, P < 0.01). Diclofenac increased stimulation
      evoked NA overflow in the absence of alpha-adrenoceptor blockade (+ 19 +/- 4%, P
      < 0.05). IV infusion of Ang II failed to enhance stimulation-evoked NA overflow
      both before and after diclofenac.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7810337
TI  - Increased rates of depression: update of epidemiological findings and analytical
      problems.
AB  - The evidence for an increased incidence of rates of depressive conditions,
      defined as depressed mood, depressive syndromes or depressive disorders, is
      reviewed. Findings from prospective studies, family genetic studies, community
      surveys, repeated cross-sectional surveys, admission data and suicide statistics
      are summarized. Methodological problems and difficulties in the analysis and
      interpretation of these results are then summarized. Because converging results
      from studies conducted with various designs, sampling and measurement strategies
      are convergent, it is concluded that the increase over time of depressive
      phenomena is a plausible finding. However, its magnitude remains unknown and is
      probably smaller than sometimes claimed. Furthermore, studies have failed to
      demonstrate that the increase in rates was specific to depressive conditions.
      Finally, it is noted that these epidemiological enquiries have failed to provide
      cues on the possible mechanisms underlying these secular changes.

PMID- 7810338
TI  - Correlation of regional cerebral blood flow equivalents measured by single photon
      emission computerized tomography with P300 latency and eye movement abnormality
      in schizophrenia.
AB  - Single photon emission tomography with the intravenous blood flow marker 99mTc
      exametazime was carried out in 14 acutely ill drug-free schizophrenic patients
      from whom P300 event-related potential, smooth eye pursuit eye tracking and
      verbal fluency were measured within a few days of scanning. Smooth pursuit eye
      movement abnormality correlated significantly with abnormal tracer uptake in
      superior pre-frontal cortex on the right and left and inferior pre-frontal cortex
      on the left. Abnormal eye movement was also associated with higher tracer uptake
      in left anterior cingulate and left posterior cingulate. P300 latency was
      significantly correlated with higher tracer uptake in left superior pre-frontal
      and left parietal regions. Verbal fluency performance was negatively correlated
      with tracer uptake in left frontal region. Eye tracking abnormality in
      schizophrenia is associated with bilateral frontal lobe disturbance and P300
      latency increase with left-sided frontal and temporoparietal dysfunction. There
      was, however, a significant inverse relation between eye tracking abnormalities
      and abnormal perfusion in the left anterior cingulate region.

PMID- 7810340
TI  - The development of the Self-Rating Inventory for Posttraumatic Stress Disorder.
AB  - In this study a newly developed Self-rating Inventory for Posttraumatic Stress
      Disorder (PTSD) is presented. The instrument consists of 47 items, reflecting DSM
      III-R criteria, associated features and items corresponding to the disorder of
      extreme stress not otherwise specified. All items are phrased in a trauma
      independent way and are measured on an intensity scale. The instrument was
      validated on 76 subjects with war-related trauma and 59 psychiatric outpatients,
      one third of whom were traumatized. Test-retest for the scale was 0.90. The
      coefficient alpha appeared to be 0.96 for the 47-items scale and 0.92 for the 22
      DSM-III-R subscale. The scale correlated significantly with the Clinician
      Administered PTSD Scale, the Mississippi Scale for Combat-related PTSD, the MMPI
      PTSD subscale and the Impact of Event Scale. The overall efficiency of the Self
      rating Inventory for PTSD was comparable to the overall efficiency of the
      Mississippi Scale and superior to the MMPI PTSD subscale. Factor analysis on the
      22 DSM-III-R items showed 4 factors, representing numbing, intrusion, avoidance
      and sleeping problems. It is concluded that the Self-rating Inventory for PTSD is
      a powerful instrument for diagnosing PTSD in survey research. The instrument
      appears to be capable of differentiating not only between PTSD and non-PTSD
      subjects but also between traumatized non-PTSD subjects and non-traumatized
      psychiatric patients.

PMID- 7810339
TI  - Rates and correlates of suicide attempts in first-admission psychotic patients.
AB  - The relationship of attempted suicide to demographic characteristics, current and
      lifetime psychiatric diagnoses, clinical history, and current symptoms was
      assessed in a sample of 184 recently hospitalized psychotic patients. Forty-three
      patients (23%) had an attempt history, and 28 (15% of sample; 65% of attempters)
      made an attempt during the episode for which they were hospitalized. Demographic
      characteristics did not distinguish attempters from nonattempters. Variables
      significantly associated with having ever attempted suicide were current
      diagnosis of unipolar major depressive disorder but not bipolar; lifetime major
      depressive episode; a history characterized by a less acute onset, lower pre
      admission psychosocial functioning, and episodes of physical violence; and a
      symptom picture characterized by greater depression, hopelessness, negative
      symptoms, hallucinations and less thought disorder. Those with a current attempt
      had significantly higher rates of lifetime history of major depression and less
      physical violence than those with past attempts only. The potential importance of
      the data for predicting future suicidal acts is discussed.

PMID- 7810341
TI  - A comparison of the drugs taken in fatal and nonfatal self-poisoning.
AB  - The objective of this study was a) to compare patterns of drug use in fatal and
      nonfatal overdoses and b) to find out if toxic drugs are overrepresented in
      overdoses with fatal outcome. A total of 179 cases of fatal overdoses in
      Switzerland (population 6.6 million) were compared with 269 medically treated
      self-poisoners from the agglomeration of Berne (population 301,630). Because of
      frequent multiple drug use, all the different compounds taken singly or in
      combination with other drugs were recorded and grouped according to drug types.
      The patterns of the frequencies of drugs used were remarkably similar in both
      groups. The majority of the drugs were psychotropics (81% in fatal and 68% in
      nonfatal overdose). Twenty-nine completed suicides were the result of drug
      combinations specifically recommended by EXIT. In the remaining cases
      benzodiazepines were used most frequently in both attempted and completed
      suicide, often in combination with other drugs or alcohol. Barbiturates were the
      only drugs recorded significantly more often in fatal overdoses (9% vs 3%). No
      significant difference was found for tricyclic antidepressants (13% vs 10%), or
      other types of drugs. The results are consistent with our assumption that drugs
      with higher toxicity would be overrepresented in overdoses with fatal outcome.
      Barbiturates, which are well known to be dangerous in overdose, were clearly
      associated with fatal overdoses, but not tricyclic antidepressants. This, in our
      view, suggests that the risk of prescribing tricyclic antidepressants should not
      be overestimated. The frequent use of benzodiazepines in completed suicide,
      however, indicates that there are no truly safe drugs in overdose.

PMID- 7810342
TI  - Incidence of post-stroke depression during the first year in a large unselected
      stroke population determined using a valid standardized rating scale.
AB  - This study describes the development of post-stroke depression (PSD)
      prospectively during the first year post-stroke in 285 unselected stroke
      patients. An appropriate unselected population-based control group without
      cerebral pathology is included for comparison. Psychiatric assessment with the
      Hamilton Depression Rating Scale (HDRS) was undertaken unmodified. PSD was
      defined as HDRS > or = 13. The one-year incidence of PSD among the 209 survivors
      able to communicate reliably at 1 month was 41%. Most cases develop within the
      first months following stroke (79%), the frequency of new cases of PSD at one
      year being 5%, a level comparable to that in the control group. Depressed and
      nondepressed stroke patients consistently scored 4 points greater on total HDRS
      than in the corresponding controls.

PMID- 7810343
TI  - Validation of Danish case register diagnosis for schizophrenia.
AB  - The ABC schizophrenia study aims at investigating sex differences in age of
      onset, symptoms and course of schizophrenic and paranoid disorders. For this
      purpose, we used case register data from Denmark and Mannheim and a directly
      examined sample of first admissions (ABC sample). The Danish case register sample
      included less clinical diagnoses of schizophrenia and more schizophrenia-related
      disorders (acute paranoid reaction, paranoid states and borderline schizophrenia)
      than the Mannheim data (case register and ABC sample). The problem therefore was
      whether the two datasets are comparable and the results are valid. For this
      reason a randomized, stratified sample of 116 patients was drawn from the Danish
      case register sample. The case notes of these 116 patients were requested from
      the hospitals where the patients had been treated and analyzed by means of a
      scoring sheet based on the Interview for the Retrospective Assessment of the
      Onset of Schizophrenia (IRAOS). The use of operationalized diagnoses of the
      CATEGO program, based on PSE items, which are integrated in IRAOS, demonstrated
      that the samples of the Danish and the Mannheim case registers and the directly
      investigated ABC sample have comparable diagnostic distributions. Possible
      explanations for the differences between the clinical and the CATEGO diagnoses in
      the Danish case register may be the frequent use of diagnoses of borderline
      schizophrenia and reactive psychoses (previously called psychogenic psychoses),
      and above all a more narrow concept of schizophrenia; in Denmark, schizophrenia
      is diagnosed relatively late, i.e., after the presence of enduring negative
      symptoms, and thus mostly after the appearance of residual state.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7810344
TI  - Emotional reactions to psychiatric patients. Analysis of a feeling checklist.
AB  - In psychodynamic milieu treatment, the relations between patients and nurses are
      the main tools for understanding and helping the patients. For this reason, it is
      important to construct methods to follow the development of relations and to
      study characteristics of helpful and nonhelpful relations. In this article, a
      checklist with feeling words given to nurses and aides in psychiatric treatment
      facilities is presented and its measurement properties are described. The
      analysis showed that the checklist as a whole measures the amount of emotional
      arousal in a reliable way. The individual feeling words have acceptable variance.
      A factor analysis gave a limited number of factors that are clinically
      understandable. The checklist seems to be well worth further study.

PMID- 7810345
TI  - Dyskinesia in mentally handicapped women: relationship to level of handicap, age
      and neuroleptic exposure.
AB  - The prevalence of dyskinesia in a randomly selected set of 61 mentally
      handicapped women with a range of diagnoses, levels of IQ and exposure to
      neuroleptics was assessed using the Abnormal Involuntary Movements Scale (AIMS).
      Overall, 64% of patients had dyskinesia on the AIMS. There was no correlation
      with neuroleptic exposure, although 43% of patients had been significantly
      exposed. There was no correlation between the presence of dyskinesia and the
      original handicapping diagnosis, and there was no increase in dyskinesia as the
      patients age increased. There was a significant increase in dyskinesia as IQ
      fell. This study backs the contention that there is a close association between
      cognitive impairment and movement disorder.

PMID- 7810346
TI  - Posttraumatic stress reactions after single and double trauma.
AB  - This study evaluated the severity and symptom profile of posttraumatic stress
      reactions of 202 adults exposed in 1988 to political violence in Azerbaijan
      and/or the earthquake in Armenia. High rates of severe posttraumatic stress
      reactions were found among the most highly exposed individuals, irrespective of
      the type of trauma. There was no difference in symptom profile for subjects
      exposed to earthquake versus violence. These similarities in severity and symptom
      profile may be attributable to common features of the exposures, which included
      experiencing life-threat and witnessing injury, multilation and death. Recent
      prior exposure to violence contributed to the severity of reaction to the
      earthquake. The high rates of chronic and severe posttraumatic stress reactions
      in Armenia constitute a major public mental health problem.

PMID- 7810347
TI  - Management of suicide attempters: what are the routines and the costs?
AB  - The services offered to a consecutive series of 97 suicide attempters (36 men and
      61 women) at a general hospital were registered by a participating observer. All
      but one case were subjected to psychiatric consultation for suicide risk
      assessment, but only 34% were evaluated by a psychiatric specialist. Fifty-seven
      percent were admitted to psychiatric inpatient care. The length of inpatient care
      varied, the average duration was 5 days for men and 14 days for women. Repeaters
      were admitted more often than nonrepeaters. The short-term compliance was
      satisfactory. The direct cost for management was evaluated based on the detailed
      quantification of care provided for each subject. The care at the hospital
      equalled 6.4% of the total budget for psychiatric inpatient care.

PMID- 7810348
TI  - A four-year prospective follow-up study of 49 eating-disordered adolescents:
      differences in course of illness.
AB  - In a 4-year prospective follow-up study of 25 anorectic and 24 bulimic
      adolescents (DSM-III-R criteria), we studied fluctuations and differences in the
      course of illness, using repeated measurement. Morgan & Russell general outcome
      categories on the Outcome Schedule were more favourable than in adult studies. Of
      all patients, 47% had good, 43% intermediate and 10% poor outcome scores after 4
      years. The groups differed significantly as to the kind and severity of disturbed
      eating behaviour and its consequences, but were rather similar in mental,
      psychosocial and psychosexual symptoms during the course of the illness. Eight
      percent of the anorectic patients became bulimic. We conclude that anorexia
      nervosa and bulimia nervosa can be considered as different symptom patterns of
      one basic eating disorder, in which preoccupation with food and a disturbed body
      image are core symptoms.

PMID- 7810349
TI  - Disappearance of gender differences in age at onset in schizophrenics with a
      familial loading.

PMID- 7810350
TI  - Towards a perspective theory of decision making and judgment.
AB  - The notion of perspectives in its literal perceptual sense is assumed to shed
      light on thinking in general and evaluative processes in decision making and
      judgments in particular. Three determinants of perspectives in thinking are
      identified: (a) the subject, i.e., subject orientation, (b) the object, and (c)
      psychological distance between subject and object. Dependent on the congruence
      between subject orientation and characteristics of the object different figure
      ground relationships are formed. When an inside perspective is adopted (the
      object is seen as affiliated with the subject) positive features form the ground
      and negative features are in the background. Conversely, when an outside
      perspective is adopted (the object is seen as separate from the subject) negative
      features form the figure and positive features are in the background. A model is
      outlined for relationships among perspectives, evaluations and external
      constraints in decision making and judgment. Empirical data from three empirical
      studies illustrate the validity of the framework described in the paper.

PMID- 7810351
TI  - Post-decision consolidation, as a function of the instructions to the decision
      maker and of the decision problem.
AB  - The effects of instructions and decision problems on post-decision processes were
      studied by varying the instructions to subjects. Subjects made a medical policy
      decision based on information on four attributes in Experiments 1-2. The subjects
      were given different instructions: (1) no instruction at all about a second
      session, (2) instruction to remember his/her decision until a session a week
      later, and (3) instruction to justify the decision at a later occasion one week
      later. The results indicated post-decision consolidation in the first group, as
      predicted by the Differentiation and Consolidation Theory (Svenson, 1992). The
      effect showed up in attractiveness restructuring in support of the chosen
      alternative on the most important attributes. The instruction to remember the
      decision until a later time increased the consolidation effect. Contrary to our
      expectations, the instruction to later justify the decision did not produce any
      consolidation. This effect was replicated in the second experiment and could not
      be interpreted as a random result. In a third experiment the decision problem was
      framed as an environmental pollution problem and it was preceded by a carefully
      designed booklet presenting arguments for and against different materials used in
      manufacturing packages for coffee. Subjects were then asked to make a choice of
      the same coffee in two different packages. The data indicated no difference in
      structural consolidation as a result of the instruction to justify or not. The
      paper concludes with a discussion pointing out the importance of the involvement
      in a decision task for decision differentiation and consolidation.

PMID- 7810352
TI  - A componential investigation of the relation between structural modelling and
      cognitive accounts of human judgement.
AB  - Structural modelling and cognitive process approaches have developed rather
      different accounts of human judgement and decision making. Two hypotheses to
      explain these differences were evaluated in the context of a judgement task, and
      formulated in terms of predictions concerning measurement of attribute
      importance. First, following suggestions made by Billings and Marcus (1983), it
      was argued that measures of judgement behaviour based on structural modelling
      reflect cognitive activity late in the judgement process, whereas measures
      derived from cognitive process approaches reflect cognitive activity early in the
      process. A new componential judgement task was developed which not only provided
      estimates of attribute importance based on structural modelling, but also two
      sets of cognitive process measures based on cognitive components assumed to occur
      early and late in the judgement process. A greater degree of convergence between
      approaches was predicted when the cognitive approach was based on activity in the
      component occurring later in the judgement process. Second, it was argued that in
      previous research subjects have had unlimited time to make their judgements,
      reducing the need for attribute importance to provide the dominant basis for
      determining processing strategy. The present experiment introduced a time
      pressure condition and, on the basis of previous research, predicted that this
      would increase the amount of information processing based on attribute
      importance, thereby increasing the convergence between estimates of attribute
      importance derived from the two approaches. The first, but not the second
      hypothesis was supported and the results were discussed in terms of their
      implications for understanding previous differences between the two approaches to
      human judgement.

PMID- 7810353
TI  - Reliability of skin biopsy pathology.
AB  - BACKGROUND: The diagnosis of skin disease by histologic examination is regarded
      as the reference standard upon which therapy and follow-up are determined. Our
      study investigated the reliability of skin biopsy diagnosis requested by family
      physicians and physicians' assistants. METHODS: Biopsy diagnoses by a community
      based pathology group were reinterpreted by our study dermatopathologist on a
      sample of 119 skin biopsies randomly selected from the 1844 biopsies performed by
      family physicians and physicians' assistants at a large Washington State health
      maintenance organization during a 4 1/2-year period. RESULTS: There were 107
      exact matches and 3 mismatches of premalignant lesions and 6 mismatches of benign
      diagnoses. In addition, two melanomas diagnosed by the community-based
      pathologists were interpreted as benign by our study dermatopathologist. A third
      melanoma diagnosed by the community-based group was interpreted as a poorly
      differentiated squamous cell cancer by the university dermatopathologist. The
      weighted kappa, 0.83, indicated excellent interrater agreement. CONCLUSION:
      Although our study showed excellent interrater concordance of skin biopsy
      interpretation, there was disagreement about three melanomas between a community
      based general pathology group and our study dermatopathologist. The melanoma
      disagreement is consistent with previous studies that found poor interrater
      agreement for early melanomas. The community-based pathologists were uncertain
      about two of these melanomas, and as part of their quality control and review
      procedures requested confirmation by an expert pathologist, who agreed with the
      melanoma diagnosis. Family physicians are justified in requesting a second
      opinion (if not automatically requested by a community laboratory) when the
      histopathologic diagnosis is not in concordance with the clinical history or
      impression or when the pathologist is unsure of the diagnosis.

PMID- 7810354
TI  - Specialty differences and the ordering of screening mammography by primary care
      physicians.
AB  - BACKGROUND: Careful attention to factors that affect women and their physicians
      is necessary to achieve the national goal that, by the year 2000, 60 percent of
      women should have had a screening mammogram in the previous 2 years. This report
      evaluates factors that differentiate primary care physicians who regularly order
      mammograms from those who do not. The study was conducted as part of a large
      demonstration project in Washington State and includes a survey of women served
      by the physicians. METHODS: We conducted a survey of primary care physicians and
      women in four counties to assess factors that influenced self-reported ordering
      of screening mammography. RESULTS: Among the 73 percent of family physicians,
      general practitioners, internists, and obstetrician-gynecologists who returned
      the questionnaire, there were more obstetrician-gynecologists (76 percent) who
      reported ordering screening mammograms in 90 percent or more of women aged 50 to
      75 years, but they cared for only 15 percent of women in the sample. Women's
      survey results confirmed the physicians' reported differences and also revealed
      demographic characteristics that distinguished populations associated with
      particular primary care specialists. These specialists differed in their
      perceptions of their colleague's mammography practices, the adequacy of insurance
      coverage, and how often they had spent an unreasonable time explaining
      mammography results. In a multivariate model of factors expected to influence
      behavior, performance of clinical breast examination rather than specialty was
      the salient factor associated with ordering screening mammography. CONCLUSIONS:
      These results suggest that the context of practice, rather than specialty type or
      beliefs about mammography, has the major influence upon behavior. To achieve
      national screening mammography goals in the Northwest, we must influence the
      context of family physicians' preventive care practices because they care for 47
      percent of women aged 50 years or older.

PMID- 7810355
TI  - A comparison of the content of army family practice with nonfederal family
      practice.
AB  - BACKGROUND: To assist with planning for education and practice, family physicians
      should know the practice content of their practices. The present study compared
      the content of nonfederal family practice with Army family practice to explore
      their differences. METHODS: This was a secondary analysis that compared the
      similar variables within two national data sets: The National Ambulatory Medical
      Care Survey and the Army's Ambulatory Care Data Base. RESULTS: Army patients were
      younger and more likely to be female than were nonfederal patients. Army family
      physicians spent more time with patients in all groups than did nonfederal family
      physicians. While 12 of the top 20 diagnosis clusters of each sector were the
      same, there were differences found in the percentages of total visits contained
      within the top 20 clusters. CONCLUSIONS: Both nonfederal and Army family practice
      have a wide variation in patients and diagnoses. The two sectors are different in
      patient age and the frequency of different diagnoses. Knowledge of these
      differences can assist with planning.

PMID- 7810356
TI  - The hypertensive patient in family practice.
AB  - BACKGROUND: Hypertension is one of the commonest reasons for visits to family
      physicians. Left untreated, hypertension and its sequelae can lead to serious
      morbidity and mortality. Most hypertensive patients have essential hypertension.
      METHODS: MEDLINE and Index Medicus literature searches of original studies, meta
      analyses, and clinical reviews were conducted for the years 1987 to the present
      to review the latest recommendations on the diagnosis and treatment of
      hypertension. Background information from articles written before 1987, accessed
      from cross-reference of the more recent articles, is occasionally cited. RESULTS
      AND CONCLUSIONS: Based on the reviewed literature, an approach to the diagnosis
      and treatment of hypertension for the family physician is presented with an
      emphasis on cost-effectiveness and nonpharmacologic treatment. Nonpharmacologic
      measures and lifestyle modification should always be part of the treatment plan,
      especially given the presence or risks of other comorbid conditions (i.e.,
      diabetes and stroke). Coexisting conditions, side-effects, ease of adherence,
      cost of medication and monitoring, and anti-left ventricular hypertrophy
      properties should be considered in selecting a pharmaceutical agent to treat
      hypertension. Several areas of further research, particularly in the areas of
      cost-effectiveness and outcomes, are needed to refine further the treatment of
      hypertension.

PMID- 7810357
TI  - Use of transdermal nicotine systems in a possible suicide attempt.
AB  - BACKGROUND: Transdermal drug delivery systems, a relatively recent development,
      are well accepted by physicians and patients because of reliability and ease of
      administration. The patch reservoirs, however, contain large quantities of drug,
      and the potential for considerable toxicity exists if they are used incorrectly.
      A case is presented of an apparent suicide attempt that involved the use of
      nicotine transdermal patches. METHODS: This case report involved a patient seen
      in the emergency department by one of the authors. Data were obtained from the
      patient's medical record while maintaining confidentiality. RESULTS: The drug
      overdose was a potentially serious one. The patient recovered fully after an
      uneventful hospital course. CONCLUSIONS: Transdermal drug delivery systems now
      deliver many drugs, several of which are quite potent. Intentional or
      unintentional misuse of the systems can result in toxicity. The physician and
      pharmacist should carefully instruct each patient in the appropriate use and
      handling of transdermal drug delivery systems.

PMID- 7810358
TI  - Guidelines for adolescent preventive services: a critical review. The American
      Medical Association Department of Adolescent Health.

PMID- 7810359
TI  - Recurrent bacterial vaginosis unresponsive to metronidazole: successful treatment
      with oral clindamycin.

PMID- 7810360
TI  - Angioedema and angiotensin-converting enzyme (ACE) inhibitors.

PMID- 7810362
TI  - Recent changes in general practice in The United Kingdom.

PMID- 7810361
TI  - Metastasis of squamous cell carcinoma of the uterine cervix to the cervical
      spine.

PMID- 7810363
TI  - Market reform of the British National Health Service: competition for better or
      for worse.

PMID- 7810364
TI  - Children's health: priorities, responsibilities, and health policy.

PMID- 7810365
TI  - Clinical prevention in primary care: everyone talks about it, why aren't we doing
      it?

PMID- 7810366
TI  - Comparing Australian and US health care systems.

PMID- 7810367
TI  - Health care reform.

PMID- 7810368
TI  - Health care reform.

PMID- 7810369
TI  - Health care reform.

PMID- 7810370
TI  - [Epidemiologic differences in delinquents relative to their psychiatric records].
AB  - We report the results of a survey carried out by us in the penitentiary from 1989
      to 1992. The aim of it was to determine a possible relationship between criminal
      behaviour and previous psychiatric pathology. A total of 121 individuals
      imprisoned from February to april 1989 were studied. Only those convicts who had
      been free taken into account. Individuals who had been imprisoned before in other
      prisons were not included in our study. A questionnaire was elaborated by us to
      carry out this survey. The convicts were tested as soon ad they came into the
      Oviedo penitentiary. The convicts were classified within two groups. In the first
      group only those who had previous psychiatric pathology were included. The rest
      of them, including drug addicts were part of the second group of our study. Our
      results show that criminal behaviour is much common between those who do not have
      suffered previously from psychiatric pathology. Furthermore, relationship between
      psychiatric pathology of the convict and his mother's criminal behaviour was
      proven. It aslo was shown between psychiatric pathology and suicide or own
      inflected injuries.

PMID- 7810371
TI  - [Psychiatric manifestations in patients with erythematosus systemic lupus].
AB  - Psychiatric diagnostics were examined in 34 patients with Systemic lupus
      erythematosus (SLE) sent to Psychiatric Unit of La Paz Hospital. At the moment of
      interview, the Adaptative disorders were the most frequent (50%), in second place
      were the Organic psychiatric disorders (38.2). In 24 patients with a follow-up
      period, all patients had chronic psychiatric disorders and the adaptative
      disorders were the most frequent too. Twenty patients had neuropsychiatric
      manifestations. We analyse the difference in SEL with and without nervous system
      involvement.

PMID- 7810373
TI  - [Validation of positive and negative symptom scale (PANSS) in a sample of Spanish
      schizophrenic patients].
AB  - We analyzed the reliability and validity issues of the Positive and Negative
      Syndrome Scale (PANSS) in a sample of 100 DSM-III-R schizophrenic patients. Our
      findings coincided with the results of the scale authors in the following points:
      1) the PANSS scores were normally distributed, 2) the positive and negative
      scales showed a good interrater reliability, 3) the construct validity was
      appropriate, 4) the positive and negative scales held a high criterion-related
      validity in relation to SAPS and SANS. Unlike to the authors of the PANSS, we
      found a modest internal consistency and an insufficient factorial validity of the
      positive scale, indicating that it is composed by several independent components.
      The data suggest that the distinction between positive and negative symptoms is
      an oversimplification, and that schizophrenic symptoms can be better
      conceptualized as being composed by, at least, three dimensional syndromes:
      positive, disorganization and negative.

PMID- 7810372
TI  - [Insomnia in asthmatic patients].
AB  - In this paper, in order to assess the prevalence and features of insomnia as a
      subjective complaint in a sample of asthmatic outpatients. (n = 43; mean age =
      36.39 +/- 12.85), items 44, 64 and 66 (that deal with insomnia complaints) of
      Derogatis' SCL-90-R (Symptom Check List 90 REvised), that was applied to the
      patients of the sample, are studied. A high prevalence of insomnia complaints is
      observed in our patients; over 70% of the sample manifests complaints of some
      type of insomnia. Insomnia complaints were higher (p < 0.0001) than in general
      population. No significant differences were evidenced according to sex and no
      correlation with age was observed in any of the items taken into account for
      insomnia complaints. A high positive intercorrelation was evidenced among the
      three items that we considered. Various factors associated with insomnia in
      asthma are discussed.

PMID- 7810374
TI  - [Cotard's syndrome: historical and conceptual aspects].
AB  - The history of the concept of Cotard's syndrome is traced from its inception in
      1880 to the present day. Nihilistic delusions were described by Cotard to refer
      to a special type of hypochondriacal delusion associated to melancholia. Although
      Cotard himself and other XIX and XX centuries' psychiatrists have considered it
      from different approaches a specific clinical entity, most of the authors
      estimate that nihilistic delusion is either a syndrome or a symptom which can
      appear in different psychiatric disorders.

PMID- 7810376
TI  - Exercise performance of reptiles.
AB  - From the vantage point of thirty years of study, we can sketch the general
      features of activity capacity and performance ability in reptiles. Extant
      reptilian groups all share low levels of maintenance metabolism and ectothermy,
      with their consequent advantages (Pough, 1980) and disadvantages. Among the
      latter is a limited capacity to expand aerobic metabolism, limited in comparison
      to the relatively great costs of terrestrial locomotion. Particularly at low body
      temperatures, reptiles outstrip their aerobic capacities with any exercise more
      intense than a slow walk. Anaerobic metabolism, particularly anaerobic
      glycolysis, can be used to fuel bursts of intense activity. As a consequence,
      however, physiological disruption and exhaustion are entailed. Under field
      conditions, many reptiles alternate long periods of quiescence or slow movement
      with very brief bursts of exertion. Other ectotherms with a similar pattern of
      metabolism have been shown thereby to extend performance beyond that supportable
      by either aerobic or anaerobic metabolism alone (Weinstein and Full, 1992). Even
      with careful alternation between these metabolic modes, reptiles remain
      particularly prone to exhaustion during vigorous activity, as least as judged by
      our mammalian frame of reference. Their capacities for burst activity and
      exertion have been shown, at least in some species, to be important determinants
      of their natural survival.

PMID- 7810375
TI  - Exercise performance of fish.

PMID- 7810377
TI  - Exercise performance of birds.
AB  - Birds are excellent endurance athletes. Not only do many birds undertake long
      migratory flights, but many do so under extreme environmental conditions:
      excessive heat, extreme cold, and the hypoxic conditions of high altitude. We are
      just now starting to understand the physiological adaptations these animals
      possess for surviving and thriving in these environments. Still, relatively few
      studies have actually been performed on exercising birds, particularly on birds
      flying under the conditions mentioned here. Furthermore, not all birds are
      capable of sustained exercise in hypoxia, heat, and cold. More work is needed to
      increase our understanding of the differences in the physiological systems that
      allow some birds to be better able to exercise under such conditions.

PMID- 7810378
TI  - Exercise performance of mammals: an allometric perspective.
AB  - We have examined aerobic exercise performance among the mammals with particular
      attention to the constraints that body size places on all aspects of muscle
      biomechanics, aerobic energetics, tissue oxygen diffusion, cardiovascular oxygen
      delivery, and pulmonary oxygen uptake. Several body-size-dependent patterns
      emerge that seemingly govern aerobic performance in mammals, with the caveat that
      at any given body size there is a range of aerobic capacities, the result of
      natural selection operating on the size-dependent "default values" of structure
      and function. Among these default values, the following apparent functional
      clusters surface: 1. In general, concentrations and pressures (e.g., of proteins
      and gases) are roughly independent of body size. Inspiratory and expiratory
      ventilation pressures, blood pressure and the partial pressures of O2 and CO2 in
      lungs, blood, and tissues do not vary with body size. Likewise, concentrations of
      hemoglobin, myoglobin, and hematocrit are independent of body size. 2. Most
      volumes and capacities scale linearly with body size (i.e., as a constant
      function of body mass). In addition to heart, lung, and total blood volumes,
      important examples relevant to exercise performance are the diffusing capacities
      for oxygen in the lung and, apparently, in the tissues. 3. Finally, most time
      dependent variables related to oxygen delivery scale allometrically with body
      mass; they are of shorter duration in small animals than in large ones.
      Biological rates, for example, Vmax of working muscle, heart and respiratory
      rates, and transit times of blood through the muscles and lungs, all vary roughly
      as the -1/5 to -1/4 power of body mass.

PMID- 7810379
TI  - Beyond the vertebrates: achieving maximum power during flight in insects and
      hummingbirds.
AB  - Hummingbirds and insects are clearly extreme aerobic athletes. Hovering
      hummingbirds and insects exhibit the highest mass-specific metabolic rates found
      in vertebrates and invertebrates, respectively. Both groups of fliers have high
      mitochondrial volume densities in their locomotor muscles, but these do not
      exceed 35-40% of the fiber volume, presumably from a need to conserve myofibrils
      for force generation. A possible adaptation to this constraint is the observed
      greater packing of the inner mitochondrial membranes than occurs in mammalian
      mitochondria. Both hummingbirds and insects show higher rates of oxygen
      consumption per unit volume of mitochondria than do mammals. Additionally, volume
      specific mitochondrial oxygen consumption in insects increases as body size
      decreases, unlike the size-independent pattern in mammals. Aerodynamic analysis
      of power output during hovering flight strongly suggests that both insects and
      hummingbirds operate with considerable elastic storage of kinetic energy, thereby
      decreasing their inertial power requirements. Both groups appear to hover with
      muscle power output close to 100 W kg-1. Muscle efficiency in hummingbirds is
      near 10%; in insects, muscle efficiency varies with body size, but at similarly
      low values. Scaling of efficiency with body size has also been reported in
      terrestrial mammals, suggesting a possible common mechanism. Both groups of
      hovering fliers can markedly increase their metabolic power inputs and mechanical
      power outputs above those required for basic hovering flight. These elite aerial
      athletes offer considerable insight into the constraints and demands on animal
      design for maximal aerobic capacity. Additionally, the similarities shown between
      the different phyla suggest the existence of common mechanisms and limitations in
      metabolic and mechanical performance. Insects in particular offer a number of
      advantages in pursuing questions such as the cause of the allometric scaling of
      muscle efficiency; this scaling can be examined within families, genera, or
      species with the additional benefit that insect muscles also perform well in
      vitro.

PMID- 7810380
TI  - Jumping ability of anuran amphibians.

PMID- 7810382
TI  - Re-evaluation of the Widal agglutination test in response to the changing pattern
      of typhoid fever in the highlands of Papua New Guinea.
AB  - In 1992 it was decided to re-evaluate the Widal slide agglutination test as a
      rapid diagnostic test for typhoid fever in Papua New Guinea. This was in response
      to an apparent increase in the number of false positive Widal slide
      agglutinations occurring using an O cut-off titre greater than or equal to 40
      which was previously shown to be appropriate in 1987. The results of the re
      evaluation indicated that the Widal test using a diagnostic cut-off titre of > or
      = 40 lacked specificity and was no longer appropriate for this population. A new
      O antibody titre of > or = 160 was recommended as a diagnostic titre for typhoid
      fever in PNG. The fall in the specificity of the Widal slide agglutination test
      over the five-year period between the initial assessment and the re-evaluation is
      due to an increase in general population antibody levels caused by the changing
      pattern of typhoid in the community. Before 1987 typhoid fever occurred as
      sporadic, isolated outbreaks and most people living in the highlands of PNG were
      immunologically naive. By 1992 typhoid fever had become a well-established
      endemic disease and many more people had been exposed to Salmonella typhi and as
      a result developed antibodies. We have been able to demonstrate clearly a
      remarkable change in the immune status of the community, in which the proportion
      of healthy individuals with a Widal tube O agglutination titre of 40 or more rose
      from 0 to 56% in the short span of five years.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7810381
TI  - Malaria and pregnancy: epidemiology, pathophysiology and control options.
AB  - Extensive research on the epidemiology, pathophysiology, and control of malaria
      during pregnancy has led to new developments and some controversies. Meanwhile,
      malaria remains a major environmental factor causing serious pregnancy
      complications, whose incidence and severity depend on gestational age, parity,
      and the level of malaria endemicity. There is no cohesive explanation for
      pregnancy-related immunosuppression, though several pathophysiological hypotheses
      have been proposed. Furthermore, the emergence and rapid spread of chloroquine
      resistance has complicated the epidemiology, and the policy on alternative
      chemoprophylaxis. Chemoprophylaxis is probably the only available option for the
      control of malaria during pregnancy in Africa. However, the best delivery
      strategy still has to be established. Daily proguanil is the best
      chemoprophylactic drug at hand. Its deployment should include constant monitoring
      for the emergence of proguanil resistance, as well as controlled supervision of
      the distribution of the drug. New control options, such as the use of insecticide
      impregnated bed nets, and intermittent targeted mass chemotherapy, require more
      operational research before they can be broadly recommended.

PMID- 7810383
TI  - The influence of Maloprim chemoprophylaxis on cellular and humoral immune
      responses to Plasmodium falciparum asexual blood stage antigens in schoolchildren
      living in a malaria endemic area of Mozambique.
AB  - We examined the impact of chemoprophylaxis on the cellular and humoral immune
      responses to polypeptides of the asexual Plasmodium falciparum blood stage
      antigens, the glutamate rich protein GLURP and Pf155/RESA, both of which in
      previous field studies have been identified as potentially protective antigens.
      The study was carried out in the Escola Primaria de Lingamo, a primary school in
      a suburban area of Maputo, Mozambique. A cohort of 392 schoolchildren (aged 7-12
      years) was randomly allocated to two equal groups, one receiving chemoprophylaxis
      with dapsone/pyrimethamine (Maloprim), the other receiving placebo every week
      from December 1989 to November 1990. The groups were then followed until November
      1991 without chemoprophylaxis. Cellular responses to immunodominant epitopes from
      Pf155/RESA and GLURP, and to non malaria antigens C. albicans and PPD, were
      assessed by lymphocyte proliferation assays in vitro. Anti-GLURP and anti
      Pf155/RESA antibodies were detected by enzyme-linked immunosorbent assay (ELISA)
      and erythrocyte membrane immunofluorescence (EMIF), and total anti-P. falciparum
      antibodies were measured by indirect fluorescent antibody test (IFAT).
      Immunological reactivities were evaluated every six months, at the end of the
      rainy season and at the end of the dry season, both during the period of
      chemoprophylaxis and during the follow-up. The antibody response rate to the
      GLURP was lower in the Maloprim group than in the placebo group during the
      intervention phase. The lymphoproliferative response rate to the malaria antigens
      was significantly lower at the end of the rainy season than at the end of the dry
      season, but the difference between the experimental group and the control group
      of schoolchildren was not statistically significant. These results suggest that
      the antibody responses to the GLURP molecule and partly to the Pf155/RESA antigen
      in this study population were shortlived and dependent on frequent boostering,
      but whether these antigens play a role in the development of natural clinical
      immunity remains open. In the experimental group of schoolchildren weekly
      chemoprophylaxis successfully reduced the parasite rate during the rainy season
      from 43% to 4%, and during the dry season from 18% to 0%. Chemoprophylaxis may
      therefore have a useful role in combination with another partially effective
      malaria control measure such as insecticide-impregnated bed nets or a malaria
      vaccine.

PMID- 7810384
TI  - Evaluation of an ELISA for combined measurement of CAA and CCA in schistosomiasis
      mansoni.
AB  - An enzyme-linked immunosorbent assay was developed for combined measurement of
      schistosome circulating anodic antigen (CAA) and circulating cathodic antigen
      (CCA). Monoclonal antibodies against CAA and CCA were used as coating and as
      fluorescein-labeled detecting antibodies in a FITC-anti-FITC system. The lower
      detection limit of the assay was 1.1 ng antigen (AWA-TCA)/ml. Serum samples of
      Schistosoma mansoni infected individuals from Zaire (n = 60) and Burundi (n = 60)
      were tested in this assay and in single-antigen ELISAs. Sensitivities of assaying
      for CAA, CCA, combined CAA + CCA, and of parallel testing for CAA and for CCA
      were calculated from titres and antigen concentrations. With serum samples from
      the heavily infected individuals (Zaire), all assays had a sensitivity of 97% or
      higher. In contrast, with serum samples from individuals from Burundi (low to
      moderate infections) it was shown that combined testing resulted in a slightly
      lower sensitivity than testing for individual antigens. By parallel testing for
      CAA and CCA, the sensitivity could be increased considerably (to 95%), however.

PMID- 7810385
TI  - Severe childhood malaria in two areas of markedly different falciparum
      transmission in east Africa.
AB  - Malaria remains a major public health challenge in sub-Saharan Africa, yet our
      knowledge of the epidemiology of malaria in terms of patterns of mortality and
      morbidity is limited. We have examined the presentation of severe, potentially
      life-threatening malaria to district hospitals in two very different transmission
      settings: Kilifi, Kenya with low seasonal transmission and Ifakara, Tanzania with
      high seasonal transmission. The minimum annual rates of severe disease in
      children below five years in both populations were similar (46 per 1000 children
      in Kilifi and 51 per 1000 children in Ifakara). However, there were important
      differences in the age and clinical patterns of severe disease; twice as many
      patients were under one year of age in Ifakara compared with Kilifi and there was
      a four fold higher rate of cerebral malaria and three fold lower rate of malaria
      anaemia among malaria patients at Kilifi compared with Ifakara. Reducing malaria
      transmission in Ifakara by 95%, for example with insecticide-treated bed nets,
      would result in a transmission setting comparable to that of Kilifi and although
      this reduction may yield early successes in reducing severe malaria morbidity and
      mortality in young, immunologically naive children, place these same children at
      increased risk at older ages of developing severe and potentially different
      manifestations of malaria infection hence producing no net cohort gain in
      survivorship from potentially fatal malaria.

PMID- 7810386
TI  - In situ immunoassay for the assessment of Trypanosoma cruzi interiorization and
      growth in cultured cells.
AB  - Interiorization and multiplication of Trypanosoma cruzi within its host cells are
      usually assessed by counting parasites in fixed and stained cover slip
      preparations, a subjective and time-consuming method. Here we describe an
      immunoenzymatic assay (ELISA) for assessing the number of internalized parasites
      in infected LLC-MK2 seed on chamber slides (NUNC). ELISA was performed employing
      a rabbit polyclonal serum against trypomastigote components (MOP) and anti-rabbit
      IgG conjugated to peroxidase. The bottom of the chamber slide was then detached
      and processed for quantification of internalized parasites by the conventional
      method. Data analysis showed a linear relationship between optical densities and
      number of internalized parasites (r2 = 93.99, p < 0.001). The assay was also
      efficient to assess inhibition of parasite interiorization induced by the
      monosaccharide NAc-D-glucosamine.

PMID- 7810387
TI  - Trypanosoma cruzi: identification of proteinases in shed components of
      trypomastigote forms.
AB  - Trypanosoma cruzi trypomastigotes were shown to predominantly release high
      molecular weight components (above 50 kDa) when allowed to shed for 1 hour in
      protein-free media. Under these conditions, parasites were not damaged or lysed,
      as was indicated by: (a) their normal mobility; (b) their retaining of some of
      the labelled proteins; (c) the unchanged pattern of biotinylated surface proteins
      after shedding. Shed components were shown to display proteinase activities,
      detected at 97 and 50/60 kDa in gelatin gels. These proteolytic activities were
      completely inhibited by E-64, indicating that they were due to cysteine
      proteinases.

PMID- 7810388
TI  - The polymerase chain reaction can reveal the occurrence of naturally mixed
      infections with Leishmania parasites.
AB  - On isolation and characterization of Leishmania parasites from Sudanese patients
      with visceral leishmaniasis (VL), four cases of mixed infections were found.
      Three of those cases were from the Eastern Sudan focus of VL. In one case the
      patient was found to be concomitantly infected with Leishmania donovani and
      Leishmania aethiopica, while the remaining three patients possessed mixed
      infections of Leishmania donovani and Leishmania major. Mixed infections were
      identified by PCR amplification of Leishmania kinetoplast DNA (kDNA) from
      parasites in culture or in original patient aspirate material and, additionally
      in the former cases by isoenzyme electrophoresis. In those cases where parasite
      culture was successful, PCR also demonstrated the rapidity with which one
      Leishmania species was eliminated from culture during continuous passage.

PMID- 7810389
TI  - Natural infection of Phlebotomus perniciosus with MON 72 zymodeme of Leishmania
      infantum in the Campania region of Italy.

PMID- 7810390
TI  - The effect of woodsmoke on the feeding and resting behaviour of Anopheles gambiae
      s.s.

PMID- 7810391
TI  - A comparison of modified McMaster and Brumpt's methods in assessment of nematode
      egg output in an N'dama cattle herd.

PMID- 7810392
TI  - The 26-kDa glutathione-S-transferases from Chinese and Philippine Schistosoma
      japonicum are identical.

PMID- 7810393
TI  - Comparative anthelminthic efficacy and safety of Caesalpinia crista seed and
      piperazine adipate in chickens with artificially induced Ascaridia galli
      infection.
AB  - The antiascarid activity of Caesalpinia crista Linn. seeds, popularly known as
      Karanjwa, was evaluated in chickens of the Fumi breed, suffering from
      artificially induced Ascaridia galli infection. Eggs per gram (EPG) counts were
      determined in the droppings of chickens prior and after treatment with powdered
      C. crista at doses of 30, 40 and 50 mg/kg of body weight along with its extracts
      in water and methanol in amounts representing 50 mg/kg of crude powder. The crude
      drug at the dose rates of 40 and 50 mg/kg and its methanol extract induced a
      significant (P < 0.001) effect on post-treatment days 10 and 15 while the 30
      mg/kg dose was efficacious (P < 0.05) on day 15 only. However, the aqueous
      extract did not show significant results. These results suggest that a 50 mg/kg
      dose of C. crista seed powder, its equivalent methanolic extract and piperazine
      (200 mg/kg) are equieffective in treating the ascarid infection of poultry. The
      crude C. crista powder appears to be potent and safer than its methanol extract
      on the basis of the side effects observed.

PMID- 7810394
TI  - Oral administration of monensin and lead to broiler chicks: effects on
      haematological and biochemical parameters.
AB  - Monensin and lead were administered separately or concurrently at different toxic
      doses to broiler chicks. Administration of lead alone did not result in a
      significant depression of haematological parameters. Administration of higher
      levels of monensin caused a reduction in haematocrit and an increase in blood
      serum levels of alanine aminotransferase, aspartate aminotransferase and
      cholesterol. Concurrent administration of monensin and lead caused a severe
      depression of haematological profiles which indicated the existence of an
      interaction between the two substances. It was concluded that concurrent
      administration of monensin and lead potentiated the toxic effects of each other.

PMID- 7810395
TI  - Effect of high- and low-nitrogen diets on cell ultrastructure in the cortical
      part of the ovine kidney.
AB  - The ultrastructure of cells of the renal cortex was studied in two groups of
      sheep fed a low- and a high-nitrogen diet, respectively. In the low-nitrogen
      group alterations were detected on the mitochondria. In the cells of the proximal
      and distal tubules, dilatation of the endoplasmic reticulum as well as
      vacuolation of the cytoplasm could be observed.

PMID- 7810396
TI  - Variations in milk somatic cell count and haematologic values of dairy cows
      during lactation.
AB  - Variations in milk somatic cell count (SCC) and haematologic values were studied
      in a dairy cow colony of the Holstein-Friesian and Hungarian Red-Spotted breeds
      (n = 23) from May 1992 to July 1993. Milk and blood samples were taken
      approximately at monthly intervals and data were assigned into ten lunar months
      of lactation. After a maximum in month I, SCC dropped abruptly in month II and
      continued to decline through the subsequent four months, then it again tended to
      increase through months VII-X. The SCCs varied within the physiological range
      throughout the lactation period parallel with red blood cells and white blood
      cells constituting a major segment of the somatic cell population. Positive
      correlations were recorded between SCC and the blood variables (packed cell
      volume, red blood cell count, white blood cell count). The lactation pattern of
      SCC was comparable to previous observations.

PMID- 7810397
TI  - Lack of effect of oxytocin given into the aorta abdominalis on corpus luteum
      function in cattle.
AB  - The aim of present study was to infuse moderate doses of oxytocin into the aorta
      abdominalis at different stages of the oestrous cycle in cattle to investigate
      its effect on the secretory function of the corpus luteum (CL). Mature heifers (n
      = 12) were synchronized with a luteolytic dose of Oestrophan. One day before the
      experiments the animals had cannulae inserted into the aorta abdominalis through
      the coccygeal artery, with the tip placed cranial to the origin of the ovarian
      artery. This allowed direct application of the drug into the reproductive tract.
      In a preliminary experiment (n = 4) we found that 40 IU of oxytocin given for 5 h
      would be a more suitable dose to enhance the peripheral concentration of this
      peptide slightly over its physiological pulses. This dose of oxytocin was infused
      in Experiment 1 (n = 4) once daily for 5 h on days 10, 11 and 12 of the oestrous
      cycle and in the same way on days 4, 8, 12 and 16 in Experiment 2. In all of
      these trials oxytocin affected progesterone or testosterone secretion measured in
      the peripheral blood. Oxytocin given into the aorta abdominalis acts not only on
      the CL but also on the uterus, oviduct, blood vessels in the reproductive tract
      etc. Hence the response of CL can be masked by the effect of oxytocin on these
      tissues. It is, therefore, assumed that oxytocin acts on the bovine CL inside the
      ovary but not as a systemic hormone.

PMID- 7810398
TI  - Bacteriologically confirmed cases of ovine epididymo-orchitis caused by Brucella
      ovis in Sub-Carpathia.
AB  - During the eradication of Brucella ovis infection from five large breeding ram
      flocks of Sub-Carpathia (The Ukraine), the genital organs of 55 rams culled
      because of seropositivity in the agar-gel precipitation (AGP) test and ELISA were
      subjected to gross pathological, histopathological and bacteriological
      examination. The results of these examinations, as well as the properties of B.
      ovis strains isolated for the first time in the region are reported. Thirty-three
      out of the 55 pairs of epididymides and testicles (60%) showed gross lesions
      (chronic epididymitis associated with the formation of spermatocele, sperm
      granuloma or abscess). From the 55 pairs of epididymides and testicles examined,
      a total of 26 B. ovis strains were isolated: of them, 24 (92.3%) originated from
      breeding rams while 2 (7.7%) from ram hoggets kept together with the breeding
      rams. Seven out of the 26 B. ovis strains (26.9%) were cultured from the
      epididymides of rams which did not show palpable epididymal and/or testicular
      lesions. It is emphasized that chronic inflammatory processes were observed in
      both epididymides even if the clinically palpable epididymo-orchitis occurred
      unilaterally. Three out of the 26 B. ovis strains were derived from AGP-positive
      but ELISA-negative, while 5 from ELISA-positive but AGP-negative rams. The
      remaining B. ovis strains were isolated from the genital organs of rams found
      seropositive both by the AGP test and by ELISA. The cultural, morphological and
      most important biochemical properties of the 26 sub-Carpathian B. ovis strains
      were identical with those of the reference strain designated Weybridge 63/290
      (NCTC 10512).

PMID- 7810399
TI  - Data on the effects of the probiotic "Lacto Sacc".
AB  - The effects of the probiotic "Lacto Sacc" on the lactic acid concentration, pH
      value and microbiological status of the intestinal content and faeces, as well as
      the ileal digestibility of different nutrients and essential amino acids were
      studied in growing pigs into which a T-cannula had been inserted surgically at
      the proximal part of the duodenum and at the distal part of the ileum. No
      differences were found between the control and the experimental group in the
      measured parameters of the chyme samples taken from the duodenum. As a result of
      "Lacto Sacc" feeding, lactic acid concentration of the ileal content increased
      from 4.77% to 7.22% while its pH value decreased significantly (P < 0.05) from
      7.39 to 6.42. The Streptococcus count was also significantly (P < 0.01) elevated.
      At the same time, the Escherichia coli count decreased significantly (P < 0.001)
      as a function of the elevated lactic acid concentration. The ileal digestibility
      of nutrients and essential amino acids improved by 1.3-16.1%. The favourable
      change observed in the microbiological status is attributed to the higher lactic
      acid concentration and the resulting lower pH, which adversely affect the
      survival of E. coli. Further studies are needed to reveal the factors responsible
      for the improved digestibility of nutrients.

PMID- 7810400
TI  - Passage of some heavy metals, nitrates and mycotoxins in the food chain.

PMID- 7810403
TI  - Detection of Mycoplasma gallisepticum antibodies in turkey blood samples by ELISA
      and by the slide agglutination and haemagglutination inhibition tests.
AB  - Comparative examination of a total of 1,030 blood samples from six turkey flocks
      of three Eastern Hungarian turkey farms was performed by the conventional
      haemagglutination inhibition (HI) and slide agglutination (SA) tests and by a
      competitive ELISA visualizing the inhibition by a positive test serum of the
      reaction between a monoclonal antibody and the specific epitope of Mycoplasma
      gallisepticum recognized by it. All the three tests detected the flocks which
      were certainly infected. The highest rate of positivity (93% of the samples
      tested) was revealed by the ELISA. By SA and HI the positivity rate was 56% and
      55%, respectively. Thirty-five per cent of the positive blood samples reacted in
      all three tests, 17% of them only by ELISA and HI, another 17% only by ELISA and
      SA, while 3% only by SA and HI. In the case of positive flocks first the SA test
      and ELISA, then the HI test and ELISA give parallel results.

PMID- 7810401
TI  - A mouse monoclonal antibody reacting with swine leukocytes: a flow cytometrical
      and immunohistochemical study.
AB  - A mouse monoclonal antibody (Mab) was prepared by immunization of Balb/c mice
      with porcine peripheral blood mononuclear cells. Its reactivity was studied by
      flow cytometry and immunohistochemistry. By flow cytometry 75-90% of blood
      lymphocytes and 93-97% of blood granulocytes showed positivity, while all
      monocytes were labelled. The specificity of the Mab was investigated further by
      immunohistochemical methods using different tissues of swine. Both cortical and
      medullary thymocytes strongly expressed the target antigen of Mab 335-2.
      Intensive staining of T cell dependent areas in the lymph nodes, spleen and
      tonsils was also observed. Many positive cells occurred in the red pulp of the
      spleen. In the non-lymphoid tissues no organ-specific staining was observed,
      except for the connective tissue which contained scattered positive cells.
      Kupffer's cells and some glial cells reacted with this Mab. These results suggest
      that this novel Mab recognizes a major antigen present on immature and mature T
      cells; however, subpopulations of myeloid cells (neutrophils, monocytes, and some
      types of macrophages) share this antigen.

PMID- 7810402
TI  - Influence of management technology and parturition on antibody levels in cows
      with bovine leukosis.
AB  - Sera from 97 Holstein-Friesian cows kept in isolation (herd I) were tested on 9
      occasions with an interval of 90 days. The cows had previously given a positive
      reaction with bovine leukaemia virus antigen in the agar gel immunodiffusion
      (AGID) test. During the period of loose housing (at tests 1-3) 0-3 cows per test
      (0-3.1%) gave a negative reaction. When the same animals were kept in the tie-in
      system (at tests 4-7) the number of negative reactors varied between 9 and 26
      (16.9-20.1%). Twenty-eight cows of herd II were tested serologically by the AGID
      test on a total of 9 occasions from day 60 before term up to postpartum day 90.
      The lowest antibody level was obtained at calving, when 7 cows gave a negative
      result in the AGID test. In three cows the decline of antibody level was so
      pronounced that their serum was negative even after postpartum day 60. One cow
      was negative even at the end of the test period (on postpartum day 90). The
      variation in serum antibody level was demonstrable also by ELISA; however, by
      that test none of the animals gave a negative result. The antibody level
      demonstrable in the milk reached its peak at calving and then it underwent a
      gradual decline; however, it did not drop below the detectability limit by the
      end of the test period. It is concluded that in bovine leukosis infected herds
      the performance of the AGID test is extremely impaired by the use of the tie-in
      housing system, as well as by a combined effect of tying in and parturition.
      Therefore, during the leukosis eradication and qualification of herds kept in a
      tie-in system, ELISA is the method that can be used, instead of AGID, with
      satisfactory efficacy even for the testing of sera.

PMID- 7810404
TI  - Effects of T-2 toxin treatment on the egg yield and hatchability in geese.
AB  - Ten groups of one-year-old geese, each including 10 layers and 3 ganders, were
      treated with T-2 toxin at doses of 0, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.8, 1.0 and
      3.0 mg/kg body weight/day for 18 days by injection into the stomach. At the toxin
      dose of 0.1 mg/kg/day, the egg yield remained unchanged while the hatching rate
      slightly decreased. T-2 toxin administered at a dose of 0.2 mg/kg/day decreased
      the hatching rate and the egg yield. The toxin dose of 0.3 mg/kg/day resulted in
      a 50% reduction of the hatching rate. The mortality rate was significant at toxin
      levels higher than 0.8 mg/bwkg/day; however, 30% of the birds survived even the
      3.0 mg/kg/day toxin dose.

PMID- 7810405
TI  - Survey of the paratenic hosts of Anguillicola crassus in Lake Velence, Hungary.
AB  - Anguillicola crassus infection of paratenic hosts was investigated in Lake
      Velence, Hungary, in October 1992. A total of 155 specimens of 8 species
      (Gymnocephalus cernuus, Lepomis gibbosus, Stizostedion lucioperca, Abramis brama,
      Alburnus alburnus, Cyprinus carpio, Pseudorasbora parva and Rutilus rutilus) were
      examined: all species proved to be infected. There were large differences in the
      prevalence of infection among fishes, but the prevalence was generally higher in
      Perciform fishes and it was the highest in G. cernuus (100%). The occurrence and
      physical stage of larvae did not depend on the size of the fish. In S. lucioperca
      the size of third stage larvae was bigger than in other fishes, and only live
      larvae were found. The comparison of Lake Velence and Lake Balaton indicates that
      the rate of larval infection in paratenic hosts of A. crassus is higher in Lake
      Velence. This might be explained by the significant ecological differences
      between the two lakes (population of intermediate hosts, water depth, salinity,
      pH).

PMID- 7810407
TI  - Proceedings of the International Symposium on Aujeszky's Disease Virus. Budapest,
      Hungary, 29-31 August 1993.

PMID- 7810406
TI  - Theileria annulata infection in neonatal bovine calves.
AB  - On an organized farm in India, 70 out of 79 cows expected to calve within 30 days
      revealed the presence of Theileria annulata schizonts and/or piroplasms in their
      peripheral blood. Similarly, 33 out of 59 calves borne to the above cows also
      exhibited T. annulata schizonts on day less than 1 to day 19 post partum. The
      cows and calves were free from Hyalomma anatolicum, an established vector of T.
      annulata, during the course of study in the winter months, when the activity of
      ticks is reduced to the minimum. The infection appears to have taken place
      antenatally.

PMID- 7810408
TI  - Aujeszky Memorial Lecture.

PMID- 7810409
TI  - Pseudorabies (Aujeszky's disease) virus: state of the art. August 1993.
AB  - The analysis of Pseudorabies (Aujeszky's disease) virus (PrV) at the molecular
      level has not only considerably increased the knowledge of PrV genes and gene
      products but has also had a major impact on the development of new vaccines and
      eradication strategies. So far, ca. 40 PrV genes have been sequenced which
      constitute approx. 60% of the PrV genome. Analysis of attenuated live vaccine
      viruses resulted in the identification of gene products that determine viral
      virulence and neurotropism which include virus-encoded enzymes, membrane
      glycoproteins, and protein(s) involved in virus particle formation. Based on
      these results the first genetically engineered live viral vaccine licensed for
      use is represented by an attenuated PrV mutant. Studies on viral surface
      glycoproteins led to the elucidation of some of their functions during the
      infectious cycle proving their role in attachment, penetration, and release of
      virions. The finding that some of the glycoproteins are nonessential for viral
      replication and can be deleted from the virus provided the basis for new
      eradication programs based on differentiation between infected and vaccinated
      animals. The recent isolation of PrV mutants unable to spread between animals
      opens up new ways for construction of safe PrV-based vector vaccines. Taken
      together, PrV can serve as an excellent example where molecular biological
      research has a direct impact on the practical aspects of controlling, and
      eventually eradicating an important animal disease.

PMID- 7810410
TI  - High-frequency intergenomic recombination plays a significant role in the
      evolution of suid herpesvirus 1 (Aujeszky's disease virus): a review.

PMID- 7810411
TI  - Is recombination of PRV vaccine strains a real problem?
AB  - Simultaneous inoculation of 50 doses of two modified live pseudorabies vaccines
      with either functional (strain Bartha) or inactivated (strain Begonia) thymidine
      kinase into piglets of 1 week of age did not induce any clinical signs of
      Aujeszky's disease. In only 3% of the cases could virus be re-isolated from organ
      specimens, namely from trigeminal ganglia or tonsils. In all samples only Bartha
      strain was recovered. By using a nested set of gII-specific primers viral DNA was
      found in 92% of the 135 samples. A deletion of 72 bp in the inverted repeats was
      used to differentiate Begonia from the Bartha strain. The genomes identified
      represented 12 times the Bartha, and 11 times the Begonia type, the remaining
      genome types could not (yet) be identified. We found no indications for the
      presence of the genomes of both viruses at the same time, nor for recombinants.
      The results suggest no selective pressure for recombinants by using vaccines with
      the same marker, i.e. gI-negative vaccines. Thus, when using gI-minus vaccines
      only, there are no indications that any real problems of recombination should
      arise.

PMID- 7810412
TI  - A bovine cell line stably expressing porcine tumor necrosis factor alpha (TNF
      alpha): growth properties and permissivity for pseudorabies virus replication.
AB  - To explore the feasibility of modifying the pathogenicity of pseudorabies virus
      (PrV), we have undertaken a program to develop recombinant PrV carrying the
      porcine tumor necrosis factor alpha (TNF-alpha) gene. We have used a cloned
      genomic DNA fragment containing the entire porcine TNF-alpha gene (Chardon et
      al., 1991), and have deleted the 3' non-translated region which is supposed to be
      a tissue-specific regulatory sequence. We have also removed the 5' non-translated
      region containing a TATA-box and binding sites for other transcription factors.
      The resulting TNF-alpha cassette has been inserted into a neomycin-selectable
      shuttle vector. This construct has been used to select MDBK cell lines harbouring
      the TNF-alpha-carrying plasmids in order to verify the production of biologically
      active TNF-alpha. One cell line thus obtained secreted 20-30 pg/10(6) cells of
      active TNF-alpha after five days in culture and exhibited normal growth kinetics.
      PrV titers on this cell line were the same as titers on cells not expressing TNF
      alpha, indicating that TNF-alpha expression in MDBK cells does not abrogate their
      permissivity for virus replication. Our results show that construction of
      recombinant PrV expressing TNF-alpha should be possible using the MDBK cell line
      as host.

PMID- 7810413
TI  - Measurement of Aujeszky's disease virus recombination in vitro under conditions
      of low multiplicity of infection.
AB  - The natural development of Aujeszky's disease virus (ADV) vaccine-derived
      recombinants has been proposed as a conceivable, although unproven, outcome of
      the practice of using modified-live vaccines on infected herds. Herpesviral
      recombination has been studied in vitro using high multiplicity of infection
      (m.o.i.) to maintain synchronous co-infection of target cells and one-step
      multiplication cycles. However, natural in vivo recombination is unlikely to
      occur at high m.o.i. with synchronous infection of all available target cells by
      both parental virus strains. Using a battery of gene-specific polymerase chain
      reaction assays, an analysis of recombination frequency at comparatively low
      m.o.i. was performed, which indicates that at low m.o.i. the rate of in vitro
      genetic recombination can be expressed as a function of the number of virus-cell
      interactions. This finding indicates that the rate of generation of recombinant
      ADV genotypes in swine infected by multiple ADV strains would be modulated by
      factors that affect the distribution of different virus strains to common target
      cells, thereby limiting or enhancing the likelihood of cellular co-infection. A
      full description of this study is available (J. gen. Virol., in press).

PMID- 7810414
TI  - Recovery of Aujeszky's disease virus recombinants from experimentally co-infected
      swine.
AB  - Tissue homogenates were obtained from swine experimentally co-infected with two
      vaccine strains of Aujeszky's disease virus (ADV). Viral isolates were derived by
      serial plaque purification directly from tissue homogenates, without an
      intervening step of isolation and amplification on cell cultures. Use of limiting
      dilutions and recovery of virus isolates as individual plaques minimized the
      likelihood of in vitro recombination serving as a confounding source of
      recombinant ADV. The tyhmidine kinase and glycoprotein X gene sequences were
      classified as wildtype or deleted, using a battery of polymerase chain reaction
      assays. On the basis of pairwise combinations of the allelic forms of the
      thymidine kinase and glycoprotein X genes, the isolates were characterized as
      recombinant and parental genotypes. The results substantiate the observation that
      ADV vaccine strains can form genetic recombinants in vivo after experimentally
      induced co-infection. A full description of this study is available (Am. J. Vet.
      Res. 54 (4) 540-545, 1993).

PMID- 7810415
TI  - Aujeszky's disease virus strains with peculiar features.
AB  - Aujeszky's disease (AD) virus strains isolated from weak colostrum-deprived
      piglets were investigated for virulence in rabbits. Most of them (5 out of 9
      investigated) proved avirulent. As clinical symptoms of AD were not observed
      during this period on the farms of origin, one can assume that the strains had a
      particular affinity for the pig fetus. It is proposed that the strains may be a
      result of recombination between the attenuated strains MK-35 (gI-) now in use as
      a live vaccine and MK-35 (gI+), used as a live vaccine until 3 years ago, as well
      as between the vaccine strain and a wild-type strain of AD virus, followed by the
      acquisition of tropism for the reproductive system. Virulent as well as avirulent
      strains were isolated in the same herd. The evaluation of a highly immunogenic
      killed AD vaccine in this complicated situation is recommended.

PMID- 7810416
TI  - Genome organization of the herpesviruses: minireview.
AB  - Fundamentally, the members of the herpesvirus family can be divided into six
      genome structure types designated by the letters A-F. Most of the viruses
      relevant to animal diseases belong to the D or E type. Whereas the biological
      function of the different DNA structures is so far unknown, studies on HSV genome
      structures indicate a rolling-circle mechanism as a mode of virus replication.
      Furthermore, the terminal repetitive segments seem to be involved in
      cleavage/packaging mechanisms and probably in the integration process of virus
      into the host genome. In the well-studied D and E type viruses a great number of
      genes are colinearly arranged and are homologous regarding their sequences. Thus
      genes encoding alpha-proteins map at least in part within the reiterated
      sequences, whereas beta- and gamma-polypeptide genes are largely located within
      the unique sequences of the long and short components.

PMID- 7810417
TI  - Function of Aujeszky's disease virus proteins in virus replication and virulence.

PMID- 7810418
TI  - Sense antisense DNA strand?
AB  - Recent evidence indicates that alphaherpesviruses express latency associated
      transcripts (LATs) from the antisense strand of immediate-early (IE) genes of the
      viral genome. It has been suggested that LATs containing extended open reading
      frames (ORFs), might be translated into (a) protein product(s). We found that a
      salient feature of some herpesvirus DNAs is a high GC preference at the third
      codon positions. The consequence of this feature is that the probability of a
      stop-codon appearing at two of the six reading frames of the DNA strand is very
      low. Therefore, the presence of an extended ORF does not necessarily mean that it
      is relevant to real translation.

PMID- 7810419
TI  - Structural features of the ribonucleotide reductase of Aujeszky's disease virus.
AB  - A gene construct of the Aujeszky's disease virus (ADV) genome was prepared and
      the DNA fragment encoding the ribonucleotide reductase was structurally
      characterized. We determined the entire DNA sequence of two adjacent open reading
      frames of the ribonucleotide reductase genes with the intergenic sequence of nine
      base pairs. From the sequence analysis we predict that Aujeszky's disease virus
      encodes a ribonucleotide reductase which comprises two polypeptides--large and
      small subunits, with sizes of 835 and 303 amino acids, respectively. Nucleotide
      and amino acid sequences of the large and small subunits of the Aujeszky's
      disease virus ribonucleotide reductase have been compared with that of other
      herpesviruses, and structural features of both proteins have been characterized.

PMID- 7810420
TI  - The neurobiology of alphaherpesvirus infections.
AB  - In this review we have tried to outline some of the recent experimental data
      which has contributed to our understanding the neurobiology of herpesviruses. We
      have attempted to draw together the threads of several different but related
      disciplines, i.e. virology, immunology, neurobiology and cell biology, to
      demonstrate how all are inextricably linked and may be used in combination to
      address some of the issues surrounding the molecular basis of herpesvirus latency
      and reactivation. In conclusion, the interaction between virus and host and in
      particular the neuron, is very complex. We have probably only scratched the
      surface here in revealing some of the many pathways and factors which are thought
      to impinge on this unique relationship. Ultimately, it is likely that a full
      understanding of that relationship will prove to be one of the most exciting and
      important milestones in biology.

PMID- 7810421
TI  - Pseudorabies virus latency: a quantitative approach by polymerase chain reaction.
AB  - Some data dealing with the establishment of a quantitative PCR assay are
      presented. The assay is based on the use of an internal standard (mimic) which
      differs from the target by a deletion of a few base pairs and which is co
      amplified with the target DNA. The resulting PCR products are labelled with
      fluorescent primers and then separated and detected by an automated sequencer. A
      highly specific and sensitive PCR assay for the envelope glycoprotein gp50 gene
      has been developed. This assay is highly reproducible with a detection limit of
      one copy of PRV DNA. Several mimics were then constructed. As a result we can
      confirm that the strategy that we have chosen is adequate for the quantification
      of low amounts of virus DNA present in latently infected swine.

PMID- 7810422
TI  - Glycoprotein I of pseudorabies virus (Aujeszky's disease virus) determines
      virulence and facilitates penetration of the virus into the central nervous
      system of pigs.
AB  - In the present study we investigated the virulence and neural spread of
      pseudorabies virus (PRV) strains with mutations in the gene encoding glycoprotein
      I (gI) in 3-week-old pigs which were intranasally infected. Mutant M303 (lambda
      125, 126) lacks amino acids valine-125 and cysteine-126 in an immunodominant
      antigenic region of gI which contains 2 discontinuous antigenic domains, whereas
      mutant virus M304 (lambda 59, 60) lacks amino acids glycine-59 and aspartic acid
      60 in a continuous antigenic domain. Mutant M301 contains a frame shift mutation.
      Both mutants M301 (gI-) and M303 (lambda 125, 126) were not virulent for pigs,
      whereas mutant M304 (lambda 59, 60) was as virulent as wild-type PRV. All gI
      mutant viruses replicated in the oropharyngeal mucosa, although M304 (lambda 59,
      60) and wild-type PRV replicated to higher titres than M303 (lambda 125, 126) and
      M301 (gI-). In contrast to M304 (lambda 59, 60) and wild-type PRV, both mutant
      viruses M301 (gI-) and M303 (lambda 125, 126) were not recovered from any part of
      the central nervous system at day 6 after infection. To study the spread of M301
      (gI-) in the central nervous system in more detail, a second experiment was done
      in which 100-fold more virus was intranasally administered and virus was
      recovered from various tissues at day 4 after infection. Again, no gI-negative
      virus was isolated from the central nervous system. We concluded that deleting
      the amino acids valine-125 and cysteine-126 decreases virulence and reduces
      neurotropism to the same degree as deleting the gI protein. In addition, gI
      negative virus does not spread in the central nervous system of pigs, probably
      because the transport of the virus across the synapse is hampered.

PMID- 7810424
TI  - Role of gp63 and gIII of Aujeszky's disease virus in the invasion of the
      olfactory nervous pathway in neonatal pigs.
AB  - The purpose of this study was to examine in which way envelope glycoproteins gp63
      and gIII of Aujeszky's disease virus (ADV) are involved in neuropathogenesis in
      pigs. The Ka strain of ADV and its single deleted mutants were examined with
      respect to invasion and spread in the olfactory nervous pathway after intranasal
      inoculation in neonatal pigs. The olfactory mucosa, olfactory bulb and lateral
      olfactory tract representing the 1st, 2nd and 3rd neuronal level of the olfactory
      pathway respectively, were examined for virus by isolation and for antigen by
      immunocytochemical localization. The Ka undeleted strain and its gIII deleted
      mutant invaded and spread to all the neuronal levels in a similar way. The gp63
      deleted mutant invaded and spread in the olfactory mucosa similarly to the Ka
      parental strain but its replication and degree of spread were diminished in all
      the levels of the central nervous system (CNS). It is, therefore, concluded that
      gp63 is involved in the neurotropism of ADV, while gIII is not.

PMID- 7810423
TI  - Interactions of Aujeszky's disease virus and porcine blood mononuclear cells in
      vivo and in vitro.
AB  - Nine pigs were inoculated oronasally with 10(8.0) TCID50 Aujeszky's disease virus
      (ADV). Blood was examined daily for the presence of a viremia during 7 days post
      inoculation. Cell-free and/or mononuclear cell (MC)-associated ADV was
      demonstrated in 7 out of the 9 pigs. The number of days on which MC-associated
      ADV was detected per pig ranged from 1 to 4 days. The number of infected cells
      ranged between 1 and 200 per 10(8) examined MC. Monocytes were found to be the
      most ADV-susceptible MC in vivo. Interactions of ADV with MC were also examined
      in vitro. Subpopulations of MC were inoculated with ADV at a multiplicity of
      infection of 20. Depending on the method of cell separation, 2 or 21% of the
      monocytes were infected. Lymphocytes were rather refractory to ADV-infection.

PMID- 7810425
TI  - Latent infection in a boar 6.5 years after experimental infection with Aujeszky's
      disease virus.

PMID- 7810426
TI  - Development of active immunity in newborn pigs with colostral antibodies by
      vaccination with gIII-deleted PRV.
AB  - Maternal antibodies interfere with active immunization of swine by gI-deleted
      pseudorabies virus [(PRV); Aujeszky's disease virus] vaccines. To test the
      hypothesis that modified-live (MLV) vaccines retaining the PRV gI and with
      deletions in the PRV glycoprotein gIII and thymidine kinase (TK) genes might be
      efficacious in circumventing colostral antibody interference, the OMNI-MARK-PRV
      (gI+ gIII- TK-) vaccine was administered intramuscularly to 13 newborn pigs with
      colostral antibodies, while 10 pigs from the same litters served as nonvaccinated
      controls. At 49 days of age, when PRV virus neutralization (VN) antibodies were
      negative and all nonvaccinated pigs as well as 10 vaccinates were latex
      agglutination test (LAT)-negative, the pigs were challenged intranasally with the
      virulent PRV(SHOPE) strain. In support of the hypothesis, it was found that
      several central nervous system and respiratory disease signs developed in 6 of 10
      nonvaccinates, with one fatality, while 2 of 13 vaccinates showed only very mild
      and transient disease signs. Nonvaccinates lost weight until post challenge day
      (PCD) 6, did not regain prechallenge weight until PCD 8, and at PCD 11 had gained
      only 4.9 pounds/pig. Vaccinates gained weight after challenge and at PCD 11
      showed a 9.4 pounds/pig weight gain. On PCD 11, the geometric mean titer (GMT)
      for VN antibodies of the nonvaccinates was 9.3, while the GMT of the vaccinates
      for VN antibodies was 49.0, showing that vaccinated pigs had been immunologically
      primed.

PMID- 7810427
TI  - Genetic and stress-mediated influence on Aujeszky's disease virus induced
      interferon-alpha production in porcine leukocytes.
AB  - The ability to produce interferon-alpha (IFN-alpha) in vitro was measured in
      blood from 200 F2-crosses between European wild boar and Swedish Yorkshire pigs,
      originating from a reference pedigree for gene mapping. A total of 200 pigs of 44
      litters, descendent from 4 boars and 22 sows, were stressed by transportation
      together with non-littermates for 5 h. Blood samples were collected from each
      individual twice, i.e. immediately before transportation and the day after
      transportation. IFN-alpha production was induced in whole blood cultures by a
      monolayer of fixed, Aujeszky's disease virus infected, porcine kidney cells. In
      general, the amount of IFN-alpha produced was significantly lower (p = 0.02) the
      day after transportation, although the ability to produce IFN-alpha showed a
      large individual variation (p < 0.001). However, both the levels of IFN-alpha
      produced and the decrease after transportation varied between the four parental
      offspring groups. Also, indications of single genes with significant effects on
      the ability to produce IFN-alpha were found. These results confirm a genetic
      influence on the ability to produce IFN-alpha. In addition, stress, such as
      transportation and mixing, may decrease the level of IFN-alpha produced.

PMID- 7810428
TI  - Serological diagnosis of Aujeszky's disease: a comparison between reactions of
      blood samples from sows and their offspring.
AB  - Blood sera from sows and their piglets were compared for their suitability for
      the serological diagnosis of Aujeszky's disease. Within a few days after
      parturition, blood and colostrum samples were collected from a total of 104 sows
      from 8 different gI-vaccinated breeding herds. Three piglets of each litter were
      bled simultaneously with their mother and again 3 weeks later. All 416 sera
      reacted positively in the screening for vaccination-induced antibodies. Using the
      gI ELISA, the sera of 16 sows and their offspring reacted positively, while 86
      sows and their piglets reacted negatively and 2 sows and their piglets showed
      reactions near the test-cutoff. By testing piglets from another 1,300 sows in 37
      farms, the practicability of the proposed method was proved. Blood samples were
      taken at intervals of 4 to 6 weeks from piglets of all sows, which had farrowed
      in the meantime. Within a six to nine months period, the serological status of a
      breeding herd could be established.

PMID- 7810429
TI  - Determination of the antigenic variability of pseudorabies virus field isolates
      with monoclonal antibodies.
AB  - Five stable hybridoma cell lines secreting monoclonal antibodies (MAbs) were
      obtained by fusing spleen cells of pseudorabies virus (strain BUK) immunized
      BALB/c mice with mouse myeloma cell line SP2/0. Plate-trapped and antibody
      trapped antigen ELISAs were done to compare the interaction of MAbs with TOP and
      "K" strains and 7 Slovak field isolates. Only 2 Slovak isolates reacted with all
      the MAbs, 3 MAbs reacted with TOP and "K" strains. One Slovak isolate gave no
      reaction with any MAbs.

PMID- 7810430
TI  - Transgenic mice harboring Aujeszky's disease virus gD gene.
AB  - Plasmid pMLP10 gp50.5 (gD) (Eloit et al., 1990) provided the sequence to
      integrate. The construct has been injected into the male pronucleus of one-cell
      mouse embryos (CBA/C5B1). A total of 1,567 microinjected embryos were transferred
      into the oviduct of pseudopregnant females (Hogan et al., 1986). PCR revealed
      that 3 out of 10 mice were born with an integrated construct; among them, 2 mice
      have integrated the construct in their gonads because 20 out of 107 (18.7%) of
      their offspring were also transgenic. This low percentage could be explained by
      germline mosaicism and/or differential mortality between transgenic and non
      transgenic embryos.

PMID- 7810431
TI  - Aujeszky's disease ELISA using baculovirus expressed glycoproteins.
AB  - The genes coding for two Aujeszky's disease virus glycoproteins, gp50 and gIII,
      were amplified by PCR and inserted into a baculovirus transfer vector. Following
      co-transfection of insect cells with a modified wild type baculovirus,
      recombinant virus clones expressing the inserted glycoproteins were detected by
      ELISA. These clones were then amplified and the expressed products used as the
      antigen for an ELISA to detect antibodies to Aujeszky's disease virus in pig
      sera.

PMID- 7810433
TI  - Serological studies in Austrian fattening pigs with respiratory disorders.
AB  - Serum samples of 253 fattening pigs out of 44 different herds with respiratory
      signs were examined for antibodies to Aujeszky's disease virus by ELISA, swine
      influenza virus (HI test), porcine respiratory coronavirus (ELISA) and porcine
      reproductive and respiratory syndrome virus (IPMA). One single case of Aujeszky's
      disease was detected at slaughter. On the other hand 24.5% of the animals proved
      to be positive for swine influenza, although no vaccine is licensed in Austria,
      and 63.6% reacted positively to porcine respiratory coronavirus. None of the sera
      showed antibodies to porcine reproductive and respiratory syndrome virus, which
      has not as yet been identified in the Austrian swine population.

PMID- 7810432
TI  - Differentiation of Aujeszky's disease virus strains isolated in Poland using DNA
      biotinylated probes.
AB  - The aim of this study was to compare 17 different Aujeszky's disease virus (ADV)
      isolates from clinical outbreaks of AD by using DNA biotinylated probes. All
      isolates were collected in Poland between 1984 and 1991. The restriction fragment
      pattern (RFP) analysis done by hybridization to NIA-3 DNA biotinylated probe
      indicated that all Polish ADV field strains can be classified as type I of Suid
      herpesvirus 1. Hybridization with BamHI fragment 7 and gI gene biotinylated
      probes revealed an unusual heterogeneity of BamHI fragment 7 in almost 50% of
      strains isolated in Poland. The nature of the molecular changes in this fragment
      will be discussed.

PMID- 7810434
TI  - Chemiluminescent detection of amplified pseudorabies virus gp50 DNA with
      immobilized probes on microtiter wells.
AB  - A highly specific and sensitive PCR assay for the envelope glycoprotein gp50 has
      been developed for the detection of PRV-DNA sequences. Primer pairs from PRV gp50
      gene were used with the enzyme uracil N-glycosylase and dUTP instead dTTP to
      prevent contamination due to PCR product carry-over. Biotinylated PCR products
      were captured in microtiter wells by specific oligonucleotide covalently linked
      to the polystyrene wells. After recognition of the biotinylated PCR product with
      a streptavidin phosphatase conjugate, a chemiluminescent detection was realised.
      Different factors influencing the binding, the hybridization and the detection
      efficiency have been tested.

PMID- 7810435
TI  - Spatial and biological characteristics of between-herd transmission of Aujeszky's
      disease virus.
AB  - The eradication of Aujeszky's disease virus (ADV) in Pennsylvania has suffered
      because the modes of viral transmission between herds are unknown. Our objective
      was to identify the major risk factors involved in viral transmission by
      comparing proportions of operation type, density, quarantine level, and
      vaccination status of neighboring herds for infected case and uninfected control
      herds. Multivariate analysis demonstrated an elevated risk of infection with
      local increases in the proportion of finishing floors. A local increase in the
      proportion of ADV-quarantined herds was shown to be a significant risk factor, as
      was an increase in the proportion of vaccinating herds. A reduced risk of
      infection was found with local increases in the number of feeder pig producer
      operations.

PMID- 7810436
TI  - Effect of vaccination on shedding of Aujeszky's disease virus in experimentally
      infected pigs and role of vaccination in herd health programmes.

PMID- 7810437
TI  - Field study for reduction of spread of Aujeszky's disease virus in finishing pigs
      with different vaccination regimes.
AB  - In a comparative field trial in feeder-finishing pigs on 8 farms with a history
      of Aujeszky's disease (AD) the incidence and spread of Aujeszky's disease virus
      (ADV) and serological effects of vaccination were investigated. Nobi-Porvac
      Aujeszky live (strain Begonia) was used either dissolved in the aqueous adjuvant
      Diluvac Forte (DF) or in Unisorve (watery solvent) to vaccinate whole feeder
      finishing units one or two times. Incidence of ADV measured by gI ELISA within
      infected finishing units was significantly reduced by the use of the adjuvant
      solvent DF. Furthermore the use of the adjuvant DF improved the efficiency of the
      vaccination as was shown by significantly higher virus-neutralising (VN) titres
      at slaughter time. The number of samples without detectable VN antibodies at the
      end of the finishing period was significantly lower in the finishing units
      vaccinated once with DF. The latter effect, though not statistically significant,
      was also seen after double vaccination in combination with the adjuvant. The
      investigation of VN antibody titres at the moment of the first vaccination
      (around 10 weeks of age) suggests that on problem farms the spread of infection
      can start earlier than that time.

PMID- 7810439
TI  - Constancy of Aujeszky's field virus antibody titres in sows repeatedly vaccinated
      with a gI-negative vaccine.
AB  - A breeding herd repeatedly vaccinated with a gI-deleted vaccine was regularly
      tested serologically for Aujeszky's field virus antibodies over a period of up to
      35 months. Of the 100 sows tested, 18 animals reacted positively with constant
      titers during the whole period of the investigation. On the other hand, there was
      no serological evidence that any of the contact animals contracted field virus
      infection.

PMID- 7810438
TI  - Economic aspects of the control of Aujeszky's disease in the European Community.
AB  - Aujeszky's disease (AD) is as much an economic problem as an epidemiological one.
      Several strategies are available for controlling the disease, and it is the task
      of the economist to compare all control options; the "best" strategy may differ
      depending on whether it is defined at the farm, regional, national or European
      Community (EC) level. After taking into account both the production losses due to
      the impact of the AD virus, and the expenditures for the control programme, the
      strategy which is most efficient from an economic point of view can be
      determined. However, the most efficient control strategy in one region cannot be
      chosen solely on the basis of the characteristics of that region, and
      circumstances in neighbouring regions have to be taken into account as well.
      Therefore, linkages between neighbouring EC regions are built into the economic
      model being developed in the EC-funded research project on Aujeszky's disease.

PMID- 7810440
TI  - Intradermal application of Aujeszky's disease virus strain Begonia with
      tocopherol-based adjuvant and a novel design injection device.
AB  - Initially the use of intradermal application of Aujeszky's disease vaccines was
      shown to be very effective. However, for thus far unknown reasons the gI-deleted
      vaccines were much less efficacious by using this route of vaccination as
      compared to gI-positive vaccines. By the use of a tocopherol-based adjuvant and
      an improved design of the intradermal injection device it now appeared feasible
      to obtain the same efficacy both in specific pathogen free pigs and in pigs with
      material antibodies as found before when intramuscular administration was
      performed. With respect to safety we found a complete lack of skin lesions, no
      adverse systemic reactions (e.g. body temperatures) and no effect on growth
      rates. Last but not least, the easiness of intradermal injections is of great
      advantage in large-scale vaccination programs.

PMID- 7810441
TI  - Eradication of bovine leukosis from a heavily infected herd by the use of own
      offspring.
AB  - In a Holstein-Friesian dairy herd (n = 1,248) kept in loose housing system and
      showing 62% prevalence of infection with bovine leukosis virus (BLV), the newborn
      calves were separated from their dams and placed into individual pens. They were
      given freeze-stored colostrum derived from a BLV-free farm and then a calf
      starter diet. Strict hygienic measures of leukosis control were observed. Serum
      samples were taken from the calves and tested by agar gel immunodiffusion (AGID)
      before and after colostrum uptake, at 2.5 and 6 months of age, and then at the
      heifer-rearing farm at 2-month intervals. Animals giving a positive reaction were
      culled. No AGID positivity occurred before the uptake of colostrum. Subsequently,
      six times as many calves became positive among the offspring of infected cows
      than among calves born to negative animals. As no separate barn was available,
      the infected farm was divided into a "black" and a "white" part with a foil to
      prevent aerogenic infection. The negative heifers being in the 7th month of
      pregnancy were placed into the "white" part. A separate calving house was
      established for them, as the joint calving house proved to be a source of
      infection. By this method a leukosis-free progeny herd was obtained from 90% of
      the heifer calves of the cow population showing a high prevalence of infection.
      In this way the original infected herd was gradually replaced.

PMID- 7810443
TI  - Pathomorphological changes caused by T-2 trichothecene fusariotoxin in geese.
AB  - T-2 trichothecene fusariotoxin was administered to 110 laying geese and 33
      ganders in the active egg production period through a tube at 2-day intervals on
      a total of 10 occasions. After the treatment, the geese were subjected to
      detailed pathomorphological examination. In the ovaries of layers, a cessation of
      follicle maturation and follicle degeneration dependent on the toxin dose were
      observed, accompanied by ovulation and consequent peritonitis in the birds that
      died and in some of those killed by bleeding. Additional findings included
      involution of the oviduct, lymphocyte depletion, necrosis and amyloidosis in the
      spleen, catarrhal enteritis, signs of colloid stasis in the thyroid and large
      numbers of secretory granules in the cytoplasm of the adrenaline-producing cells
      of the adrenal gland. In the ganders, toxin administration did not reduce the
      intensity of spermatogenesis but in the spleen, intestine and endocrine glands it
      caused changes similar to those seen in the layers.

PMID- 7810442
TI  - Perinatal oestrogen syndrome in swine.
AB  - Perinatal oestrogen syndrome (F-2 fusariotoxicosis occurring at the perinatal
      age) was studied in large pig herds and in animal experiments. The disease
      markedly lowered the conception rate of sows and gilts, and increased the number
      of repeat breeders. Litter size decreased and the number of stillbirths rose.
      Both the newborn piglets and the stillborn fetuses showed swelling of the vulva
      and teats and oedematous infiltration of the perineal region, ventral part of the
      abdomen and umbilicus, often accompanied by exudative-crusted inflammation, then
      necrosis of the teats. The number of piglets with splayleg and trembling
      increased. Gross and histopathological examination revealed enlargement of the
      ovary and uterus, with signs of follicle maturation in the ovary, glandular
      proliferation in the endometrium and epithelial proliferation in the vagina in
      addition to oedema and hyperaemia. In newborn piglets, the signs of
      hyperoestrogenism could be induced also experimentally, by feeding an F-2 toxin
      containing diet to pregnant sows. Intrauterine toxin effect was found to be
      primarily responsible for inducing the syndrome in newborn piglets. Because of
      its lower quantity, F-2 toxin excreted in the sow's milk is assumed to have a
      secondary role.

PMID- 7810444
TI  - Effect of acute selenium toxicosis on the lipid peroxide status and the
      glutathione system of broiler chickens.
AB  - The effect of acute oral selenium toxicosis on the rate of lipid peroxidation, on
      the amount of reduced glutathione as well as on glutathione-peroxidase activity
      of the blood (plasma and red blood cells) and liver was studied in broiler
      chicken. Cockerels (28-day-old) were treated with selenium (4.85 mg/kg b.w.)
      administered intraoesophageally in the form of sodium selenite. Samples were at
      the onset of clinical signs (3 h after treatment) and 2 and 4 h thereafter. The
      malondialdehyde content of the blood plasma rose significantly (P < 0.05) at the
      onset of clinical symptoms but decreased later. Malondialdehyde content of the
      liver was higher than the control value at the first sampling (P < 0.01) and
      steadily increased later. Reduced glutathione content did not change
      significantly in the blood plasma and liver. Glutathione peroxidase activity of
      the RBC was significantly elevated (P < 0.01) only at the first sampling (3 h
      after treatment) and decreased to the control level thereafter. Acute oral
      selenium toxicosis increases the rate of lipid peroxidation in a short period of
      time (7 h) without exerting a significant effect on the glutathione system.

PMID- 7810445
TI  - Elimination and metabolism of triiodothyronine depend on the thyroid status in
      the brain of young chickens.
AB  - The hypothyroid chicken brain has been found to preserve more triiodothyronine
      (T3) than expected from plasma T3 levels. A possible explanation is that the
      elimination of T3 from the hypothyroid brain is decreased. In the present
      experiments, the elimination rate of T3 was compared in surgically
      thyroidectomized animals and sham-operated controls. It was found that both T3
      coming from the plasma and T3 derived locally in the cells from thyroxine have a
      significantly lower elimination rate in thyroidectomized chickens than in sham
      operated ones. Therefore it is concluded that the adaptation of the brain to
      hypothyroid conditions is partly regulated by reducing the loss of the active
      thyroid hormone (i.e. T3) via metabolic and tissue-to-plasma exchange.

PMID- 7810447
TI  - Evaluation of testosterone response to intramuscular injection of GnRH and its
      correlation with sperm quality parameters in cockerels.
AB  - Eight 40-week-old New Hampshire cockerels (average liveweight: 3.10 +/- 0.2 kg)
      were used for studying the testosterone response to a single intramuscular dose
      (5 micrograms/kg b.w.) of exogenous 6D-Phe gonadotropin releasing hormone (GnRH).
      Serum samples were collected at 15-min intervals during the first hour and at
      half-hour intervals up to two hours post injection. The semen samples were
      collected 24 h before GnRH treatment. Testosterone peaks were found 45 to 60 min
      after the treatment. The coefficient of correlation between the semen quality
      parameters and the testosterone response to GnRH was evaluated both by Rank
      correlation and by multiple regression analyses. Rank correlation showed moderate
      but not significant values while multiple regression analyses showed a close
      correlation (multiple R = 0.72). The results show that testosterone response to
      GnRH may be used as a marker of semen quality in cockerels.

PMID- 7810446
TI  - Effect of vitamin E treatment on early postnatal changes of vitamin E status of
      chicken.
AB  - Day-old chickens were treated with 3.25 mg vitamin E/bird/day per os, via the
      drinking water, for two weeks. The vitamin E content of both the liver and the
      blood plasma was significantly higher in the treated chickens than in the
      untreated controls. The positive effect was more pronounced in the liver than in
      the blood plasma.

PMID- 7810448
TI  - Protein content and amino acid composition of the uterine milk in swine and
      cattle.
AB  - The protein content and amino acid composition of the uterine milk of swine and
      cattle were analyzed using slaughterhouse-derived samples. For both species, the
      majority of the dry matter of uterine milk consisted of materials of protein
      nature (swine: 68.1%, cattle: 73.3%). Free amino acids constituted approximately
      0.3% (swine) and 0.5% (cattle) of the dry matter. In the uterine milk of sows,
      the high ratio of serine, glycine and acidic amino acids (overall ratio: 65%) was
      remarkable. No such striking values were found for the bovine species; however,
      the uterine milk of cows was also characterized by the predominance of acidic
      amino acids. Total amino acid content of the uterine milk was compared with that
      of freshly milked colostrum. With the exception of glutamic acid in sows and
      methionine and glutamic acid in cows the uterine milk and the colostrum had
      identical amino acid content. It is concluded that the embryotroph can be
      considered a transition between the blood and the colostrum.

PMID- 7810449
TI  - Supports/training for Alzheimer's caregivers. State Department of Mental Health
      and Mental Retardation.

PMID- 7810450
TI  - Alabama physicians face managed care and powerful networks.

PMID- 7810451
TI  - A short history of elitism.

PMID- 7810452
TI  - Now what?

PMID- 7810454
TI  - Eugenics revisited: heredity deafness and genetic technology.

PMID- 7810453
TI  - Stark II: the health care reform proposal that passed.

PMID- 7810455
TI  - Behavior problems with deaf Dutch boys.
AB  - During an investigation into behavioral problems of deaf children, 41 deaf boys
      were compared to a large group of hearing children of the same age. T.M.
      Achenbach's Child Behavior Checklist was used for data collection and analysis.
      It appeared the deaf boys had more behavioral problems overall but that they were
      no more often disturbed than their hearing counterparts. Internalizing and
      externalizing behavioral problems emerged with greater frequency in the deaf
      group. Younger deaf boys showed more behavioral problems than older deaf boys
      with differences in age emerging as discriminating factors.

PMID- 7810456
TI  - Deaf Finnish adults' views of their society: knowledge, satisfaction, values and
      attitudes.
AB  - Deaf Finnish adults were studied as a language minority to assess their knowledge
      of Finnish society. This study addresses their level of satisfaction with and
      participation in Finnish society. Information was obtained from 63 individuals.
      The complete sample included 32 men and 31 women. The age range was from 17 to
      78, with a mean age of 41 years. Females tended to score higher than males on
      measures of knowledge with younger respondents scoring higher than older
      respondents. Men tended to show higher levels of overall satisfaction, with no
      age differences on this construct. Satisfaction was expressed with the Finnish
      Republic, services for the deaf, law and order and wages earned. Dissatisfaction
      was expressed with the cost of living, education and the lack of equality with
      the hearing.

PMID- 7810457
TI  - The effectiveness of an intervener model of services for young deaf-blind
      children.
AB  - Project Validation of the Intervener Program (VIP) studied and documented the
      effectiveness of the Intervener Service Model which provides the services of a
      paraprofessional (called an intervener) to families of young children who are
      deaf-blind. The intervener provides auditory, visual, and tactile stimulation for
      the child and helps the child develop interactive behaviors instead of isolated,
      defensive, or self-stimulatory behaviors. The intervener also enables the parents
      to obtain much needed respite. Project VIP obtained abundant quantitative and
      qualitative data on the effectiveness of the Intervener Service Model. The data
      strongly support the need for Intervener Services for young children who are deaf
      blind and their families.

PMID- 7810458
TI  - The relationship between emotional-behavioral functioning and personal
      characteristics on performance outcomes of hearing impaired students.
AB  - Performance outcomes, emotional-behavioral functioning and other selected
      variables of deaf and hard of hearing students ages 11 through 21 years
      representing a variety of educational placements and levels of hearing loss were
      investigated. Results showed that deaf and hard of hearing students generally
      scored high on the outcome competencies and emotional-behavioral functioning was
      within the normal range. Statistically significant correlations were found
      between many of the performance outcomes and emotional-behavioral functioning.
      Multiple linear regression analyses revealed that the composite score of the
      emotional-behavioral scale was a statistically significant predictor for four of
      the outcome categories. Mainstreamed students scored higher on all of the outcome
      categories than students in other program placements, but there was no difference
      in emotional-behavioral functioning between groups. Level of functioning appeared
      to be unaffected by the degree of the students' hearing loss.

PMID- 7810459
TI  - Assessing the efficacy of an academic hearing peer tutor for a profoundly deaf
      student.
AB  - This study assessed the efficacy of using a hearing peer tutor to provide math
      instruction for a profoundly deaf sixth-grade girl. Instruction was provided for
      twenty minutes each day. A changing criterion design was employed to measure the
      tutee's progress across four math objectives she had not previously mastered. The
      peer tutoring intervention was highly successful, with the tutee meeting the
      criterion of 70 percent accuracy for three consecutive days for each of the four
      curriculum objectives after only a brief period of intervention. Peer tutoring is
      discussed as a potentially useful vehicle for mainstreaming deaf children.

PMID- 7810460
TI  - Play behavior and communication between deaf and hard of hearing children and
      their hearing peers in an integrated preschool.
AB  - Sixty preschoolers (30 deaf and hard of hearing, 30 hearing) were observed in
      their integrated school during "centers" and outdoor play. Half the children
      experienced auditory communication and half total communication modes of
      communication. All children had known their classmates for six months to three
      years. It was found that all children preferred to play and communicate with same
      hearing status children, however 63% of all children communicated with children
      of other-hearing status. Amounts of social play and communication differed
      somewhat between the two communication environments, and context of interaction
      was related to the behavior and communication of children who were deaf and hard
      of hearing. Implications are discussed for the education of young children who
      are deaf and hard of hearing--specifically that educational and social benefits
      accrue to those who are integrated throughout the school day (across context) and
      have access to hearing classmates and classmates who are deaf and hard of
      hearing.

PMID- 7810461
TI  - Classroom attributes and achievement test scores for deaf and hard of hearing
      students.
AB  - This study examined reading comprehension and mathematics computation achievement
      of deaf and hard-of-hearing students in a variety of school settings. Data were
      collected by Gallaudet University's Center for Assessment and Demographic Studies
      during its 1990 standardization of the 8th Edition Stanford Achievement Test.
      Descriptive and inferential statistical methods were used to analyze the
      relationships among achievement scores, classroom attributes, and demographic
      factors associated with achievement. Based on the results of this study,
      inclusion with hearing students in regular classrooms is related to a variety of
      demographic factors. When reading comprehension and mathematics computation
      scores are adjusted for these factors, they are higher for the deaf and hard-of
      hearing students in regular classrooms. However, it is not known whether the
      higher achievement is due to inclusion or whether students were selected for
      inclusion due to their higher achievement levels.

PMID- 7810462
TI  - Deaf autonomy and deaf dependence. The early years of the Pennsylvania Society
      for the Advancement of the Deaf.
AB  - Deaf history is more complex and ambiguous than previous studies have indicated,
      and historians' preoccupation with the manual-oral controversy has precluded a
      full understanding of deaf people's lives. The historical interests and organized
      efforts of the Pennsylvania Society for the Advancement of the Deaf (PSAD)
      transcended language issues and focused on balancing the risks and the benefits
      of deaf self-determination. One hundred years ago, PSAD's leaders concentrated
      their efforts on philanthropy and lobbying for the general good of deaf
      Pennsylvanians, while remaining silent on controversies over deaf education. In
      effect, they accepted oralism and hearing hegemony in education in exchange for
      deaf autonomy and improvement in other areas of life. If the PSAD's experience is
      typical of other state organizations, simple historical models that focus on the
      actions of hearing oppressors obscure the actual creativity, struggles, and
      sophistication of America's deaf leaders.

PMID- 7810463
TI  - The numb arm and hand.
AB  - Trauma and compression along the course of the median, ulnar or radial nerve from
      the brachial plexus to the fingers may cause pain, weakness, numbness or tingling
      of the upper extremity. Diabetes, smoking, alcohol consumption, rheumatoid
      arthritis and hypothyroidism are risk factors for nerve entrapment, although
      these disorders typically produce bilateral symptoms. Carpal tunnel syndrome, the
      most common nerve entrapment condition, results from median nerve compression at
      the wrist. The diagnosis is suggested by decreased pain sensation and numbness in
      the thumb and index and middle fingers; symptoms are reproduced by wrist
      hyperflexion and median nerve percussion. Volar splinting and steroid injection
      often ameliorate symptoms. Decreased sensation of the little finger and the ulnar
      aspect of the ring finger, along with intrinsic muscle weakness, may be caused by
      cervical radiculopathy, thoracic outlet syndrome or compression of the ulnar
      nerve above the elbow (cubital tunnel syndrome) or at the wrist (ulnar tunnel
      syndrome). Electromyography and radiography may help differentiate these
      conditions. Radial tunnel syndrome occasionally accompanies inflammation of the
      common wrist extensors and lateral epicondylitis ("tennis elbow"). A radial nerve
      block can help exclude concomitant radial tunnel syndrome in patients with
      symptoms of lateral epicondylitis.

PMID- 7810464
TI  - Sexuality in the nursing home patient.
AB  - Sexual behavior is an integral part of human existence. The changes of aging
      affect all stages of sexual response in both men and women, but the capacity to
      enjoy sex is not altered with age. Surveys demonstrate that while sexual activity
      declines with age, a significant proportion of elderly persons, including those
      in nursing homes, remain sexually active. Barriers to sexual expression for
      residents of long-term care facilities include lack of privacy, chronic illness,
      lack of a willing partner, loss of interest, attitudes of physicians and staff,
      feelings of unattractiveness and an insufficient understanding of sexuality.
      Physicians can help remove barriers to sexual expression for elderly nursing home
      residents by improving privacy, educating staff, allowing conjugal or home
      visits, assessing decision-making capacity in cognitively impaired elderly
      persons, encouraging several forms of sexual expression, providing information
      and counseling about sexuality to interested patients, and evaluating patients'
      complaints about sexual functioning.

PMID- 7810466
TI  - Screening for lead exposure in children. U.S. Public Health Service.

PMID- 7810465
TI  - Cholesterol screening in adults. U.S. Public Health Service.

PMID- 7810467
TI  - Diagnostic ultrasound in labor and delivery.
AB  - Clinical questions often arise suddenly and at odd hours during the intrapartum
      period. Many questions can be answered immediately by making use of readily
      available diagnostic ultrasonography. The verification of fetal life, fetal
      number and fetal presentation, amniotic fluid assessment and determination of
      placental location are important in maternal-fetal care. Sonographic skills
      facilitate the performance of certain procedures, including external version of
      the breech fetus, intrapartum twin management and amniocentesis for lung-maturity
      testing or culture in cases of suspected chorioamnionitis. Sonography can be
      helpful in the evaluation of possible placental abruption, but management of this
      condition remains clinical and should not be affected by a negative sonographic
      scan.

PMID- 7810468
TI  - Subdural empyema.
AB  - Despite the availability of new broad-spectrum antibiotics, sinusitis
      occasionally causes significant morbidity and mortality. One serious complication
      of paranasal sinusitis is subdural empyema, a fulminating intracranial disease
      that is invariably fatal if not treated. The symptoms of subdural empyema may be
      mild and may be the same as those associated with sinusitis, or the infection may
      result in alteration of the level of consciousness and focal neurologic deficits.
      Rapid recognition and treatment of subdural empyema is extremely important.
      Before magnetic resonance imaging became available, computed tomography was used
      for rapid diagnosis of this infection. Magnetic resonance imaging, however, is
      now becoming the diagnostic tool of choice. Neurosurgical intervention and high
      doses of intravenously administered antibiotics are the mainstays of treatment.
      If treatment is initiated as soon as the diagnosis of subdural empyema is made,
      the patient has a good chance of recovering with no, or only slight, neurologic
      defects.

PMID- 7810469
TI  - Analgesia, sedation and paralysis in the intensive care unit.
AB  - Patients admitted to the intensive care unit often experience some degree of pain
      and frequently are anxious, confused or delirious. Relief of pain, anxiety and
      agitation is important for effective patient care. Initial attention should be
      directed toward eliminating organic causes of delirium. Opioids are the
      cornerstone of analgesia, while benzodiazepines and haloperidol are commonly used
      for sedation and relief of agitation. When sedative agents fail to control
      agitation and effective ventilation of the patient is compromised, it may be
      appropriate to pharmacologically paralyze the patient.

PMID- 7810470
TI  - Management of genital herpes.
AB  - Genital herpes affects over 30 million persons in the United States. Genital
      herpes has three distinct presenting syndromes, depending on the patient's immune
      status with regard to the herpes simplex virus. Current diagnostic strategy
      relies on clinical findings and the selective use of viral culture. Acyclovir is
      the drug of choice for the treatment of genital herpes. Drug resistance is an
      increasing problem, requiring the use of newer agents. Treatment of the
      immunocompromised patient is a special area of concern. In addition to the
      medical aspects in the treatment of genital herpes, psychosocial requirements
      should also be addressed.

PMID- 7810471
TI  - Drug treatment of insomnia: indications and newer agents.
AB  - Insomnia is a symptom that should be treated according to the underlying
      etiology. It is more common in elderly individuals and in women. Common causes of
      insomnia include acute situational factors, psychiatric disorders, use of various
      medications and illicit drugs, and medical disorders that cause pain, dyspnea or
      nausea. Pharmacotherapy should be generally restricted to use of the
      benzodiazepines, imidazopyridines (zolpidem) and occasionally tricyclic
      antidepressants. As a rule, hypnotic drugs should be used for less than two weeks
      to one month.

PMID- 7810472
TI  - AAP issues guidelines on hyperbilirubinemia in healthy, term newborns.

PMID- 7810473
TI  - Ten steps to healthier patients in 1995.

PMID- 7810474
TI  - Obstetric ultrasound in family practice.

PMID- 7810475
TI  - Family physicians and the critically ill patient.

PMID- 7810476
TI  - Family physicians and the primary care product.

PMID- 7810477
TI  - Sucralfate for aphthous ulcers.

PMID- 7810478
TI  - Concern about use of narcotics for pain in sickle cell anemia.

PMID- 7810479
TI  - Potential hazards of generic antidepressants in the elderly.

PMID- 7810480
TI  - Carpal tunnel syndrome, work return and manipulation therapy.

PMID- 7810481
TI  - Topical chloroform and postherpetic neuralgia.

PMID- 7810482
TI  - The single-payer system: bogeyman or straw man?

PMID- 7810483
TI  - Comparison of quantitative angiographically derived and measured translesion
      pressure and flow velocity in coronary artery disease.
AB  - Although quantitative coronary angiography (QCA) has been used to determine
      lesion severity, angiographically derived parameters of translesional physiology
      have not been compared with those directly measured in the same patients. Thus,
      the aim of this study was to correlate QCA-derived translesional pressure and
      flow data with directly measured data in patients. QCA (DCI-ACA program),
      translesional pressure gradient (2.2Fr fluid-filled tracking catheter), and
      intracoronary Doppler flow velocity (0.018-inch FloWire) measurements were
      simultaneously performed in 28 arteries (25 patients). Mean diameter stenosis was
      51 +/- 2.3% (range 29 to 73). No patient had left ventricular hypertrophy or
      valvular heart disease. The arteries studied were left anterior descending in 14,
      circumflex in 8, and right coronary in 6 patients. Stenotic flow reserve and
      baseline and maximal gradients were calculated by the DCI program. Coronary flow
      reserve and baseline and maximal hyperemic gradients were also directly measured
      distal to the stenosis after administration of intracoronary adenosine (12 to 18
      micrograms). QCA-derived pressure gradients did not correlate with the measured
      gradients at baseline (r2 = 0.005; p = 0.73) or at maximal hyperemia (r2 = 0.1; p
      = 0.13). No correlation was found between the QCA-predicted flow reserve and the
      coronary flow reserve measured distal to the stenosis (r2 = 0.02; p = 0.46).
      Furthermore, stenotic flow reserve and measured gradient were not significantly
      correlated (r2 = 0.1; p = 0.16). In this range of stenoses of intermediate
      severity, there was no correlation between the measured pressure gradient or
      coronary flow reserve and lesion diameter or cross-sectional area by
      QCA.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7810484
TI  - Diagnostic accuracy of heart rate-adjusted ST segments compared with standard ST
      segment criteria.
AB  - We compared the accuracy of ST segment/heart rate (ST/HR) index with that of
      standard criteria (> or = 0.1 mV horizontal/downsloping ST depression 80 ms after
      the J point) in 121 patients who had undergone angiography (49 with > or = 1
      lesion with > or = 50% stenosis) and 50 clinically normal subjects. All exercise
      tests used the Cornell protocol and computer measurements of maximal ST
      depression 80 ms after the J point. Thresholds with equal specificity to standard
      criteria were determined for ST/HR index using each of the 2 normal groups (those
      who were normal by angiography and those who were clinically normal). In using
      only patients who underwent angiography, we found that the ST/HR index had a
      sensitivity that was not significantly greater than that of standard criteria
      (standard criteria 51%, ST/HR index 59%; p = 0.21). However, the receiver
      operating characteristic curve area increased from 64 +/- 4 to 68 +/- 4 (p <
      0.02). When clinically normal subjects were used instead of patients without
      angiographic disease, there was a clearly discernible improvement in sensitivity
      of ST/HR index over standard criteria (standard criteria 51%, ST/HR index 69%; p
      < 0.05). The associated curve areas were 69 +/- 4 and 79 +/- 3 (p < 0.001).
      Therefore, accuracy of the ST/HR index was marginally better than standard
      criteria only in patients who underwent angiography. When clinically normal
      subjects were used, the accuracy of the ST/HR index was definitely better than
      standard criteria. We conclude that the demonstration of improved accuracy of the
      ST/HR index depends on the population being tested.

PMID- 7810485
TI  - Relation of angiographically defined coronary artery disease and plasma
      concentrations of insulin, lipid, and apolipoprotein in normolipidemic subjects
      with varying degrees of glucose tolerance.
AB  - We investigated the association between hyperinsulinemia and changes in lipid,
      lipoprotein, and apolipoprotein that would increase the risk of coronary artery
      disease (CAD) independent of glucose tolerance. A coronary angiogram was recorded
      in 127 male subjects, including 41 with normal glucose tolerance, 41 with
      impaired glucose tolerance, and 45 with non-insulin-dependent diabetes mellitus
      (NIDDM). Subjects were divided into 2 groups according to results: the group with
      CAD (n = 94) and the group with normal coronary arteries (n = 33). All subjects
      were normolipidemic (total cholesterol < 230 mg/dl and triglycerides < 150
      mg/dl). The CAD group had a significantly lower plasma level of high-density
      lipoprotein (HDL) cholesterol and apolipoprotein A-I (apo A-I) and a higher level
      of apolipoprotein B (apo B) than the normal group with normal glucose tolerance.
      In considering subjects with impaired glucose tolerance or NIDDM, the CAD group
      had a significantly lower plasma level of HDL cholesterol and apo A-I and a
      significantly higher plasma level of total cholesterol, triglycerides, and apo B
      than the normal group. In each of the subjects with normal and impaired glucose
      tolerance, and NIDDM, the elevation of plasma insulin concentration during both
      the complete test period and the early phase of an oral glucose challenge was
      significantly higher in the CAD than in the normal group. In all subjects, graded
      reductions in HDL cholesterol and apo A-I and graded increases in plasma total
      cholesterol, triglycerides, and apo B were observed with increasing tertiles of
      the postglucose challenge measurements of insulinemia.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7810486
TI  - High-density lipoprotein subfractions as markers of early atherosclerosis.
      PCVMETRA Group. Prevention Cardio-Vasculaire en Medecene du Travail.
AB  - Although the inverse relation between high-density lipoprotein (HDL) cholesterol
      concentration and the risk of ischemic heart disease is well established, little
      is known about the relation of HDL subfractions HDL2 and HDL3 or lipoprotein A-I
      and A-I-A-II to extracoronary disease, particularly at its silent phase before
      the appearance of clinical lesions. We investigated the potential influence of
      HDL subfractions as risk markers, among the other main lipid and nonlipid risk
      factors, by assessing early atherosclerotic plaques detected by 3 ultrasound
      imaging sites in 181 hypercholesterolemic symptom-free men. No plaques were found
      in 36% of the patients, but plaques were found at carotid, aortic, and femoral
      sites in 24%, 40%, and 46% of subjects, respectively. Data were analyzed using
      univariate comparisons and multiple logistic regression. According to the
      logistic analysis, plaques were associated (1) with blood pressure (p = 0.008)
      and low-density lipoprotein (LDL) cholesterol (p = 0.02) in the carotid arteries;
      (2) with age (p = 0.0005), triglycerides (p = 0.002), and cigarette smoking (p =
      0.02) at the aortic site; and (3) inversely with HDL3 cholesterol (p = 0.0008)
      and positively with cigarette smoking (p = 0.004), and age (p = 0.04) in the
      femoral site. The number of arterial sites affected (0, 1, 2, and 3) by plaques
      was inversely associated with HDL3 cholesterol (p = 0.001), and positively
      associated with smoking (p = 0.002), blood pressure (p = 0.002), LDL cholesterol
      (p = 0.003), and age (p = 0.006).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7810487
TI  - Evidence that homocysteine is an independent risk factor for atherosclerosis in
      hyperlipidemic patients.
AB  - In 482 patients sequentially referred for diagnosis and therapy of
      hyperlipidemia, our specific aim was to determine the prevalence of
      homocysteinemia, to assess whether it was independently associated with
      atherosclerotic vascular disease, and to determine how effectively high
      homocysteine could be treated with folic acid and pyridoxine. Of the 482
      patients, 18 (3.7%) had high homocysteine (> or = 16.2 mumol/L, median = 19), 31
      had high cystathionine (> or = 342 nmol/L) with normal homocysteine (median =
      12), and 433 had normal cystathionine and homocysteine (median = 9). Of the 18
      patients with high homocysteine, 13 (72%) had atherosclerotic vascular disease,
      much higher than the 44% (192 of 433 patients) with normal homocysteine (chi
      square = 5.4, p = 0.02). In the 18 kindreds with a homocysteinemic proband, 14
      (78%) had > or = 1 first-degree relatives with atherosclerotic vascular disease
      before age 65, compared with 50% (215 of 433) of the families where the proband
      had normal homocysteine (chi-square = 5.5, p = 0.02). In the 482 patients already
      at high risk for atherosclerotic vascular disease by virtue of hyperlipidemia,
      when assessed by logistic regression, homocysteine was an independent positive
      predictor of atherosclerotic vascular disease (p = 0.007); relative risk for
      atherosclerotic events was 2.8 times higher (p = 0.0004) in patients with top (>
      or = 11.4 mumol/L) than with bottom (< 6.9 mumol/L) quintile homocysteine. After
      15 weeks of folic acid (5 mg/day) and pyridoxine (100 mg/day) therapy in 10
      patients with high homocysteine, median homocysteine normalized, decreasing from
      18 to 11 mumol/L (p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7810488
TI  - Arrhythmias after cardioverter-defibrillator implantation: comparison of
      epicardial and transvenous systems.
AB  - Surgery for implantable cardioverter-defibrillators can cause postoperative
      exacerbation of ventricular and atrial arrhythmias. It is not known whether the
      techniques of electrode implantation (epicardial vs transvenous) influence the
      incidence of arrhythmia exacerbation. We reviewed the postoperative course of 229
      consecutive patients who received either epicardial (n = 119) or transvenous (n =
      110) implantations from 1984 to 1994. Exacerbation of ventricular tachycardia
      (VT) was defined as an increase in the number of sustained VTs during the
      postoperative versus the preoperative 2 weeks. Of the entire cohort, 18 patients
      (8%) developed exacerbation of VT after operation, which was more frequent in
      patients with epicardial than with transvenous implantations (12% vs 4%, p <
      0.03, odds ratio 3.5, 95% confidence interval 1.0 to 13.2). New-onset atrial
      fibrillation occurred in 15% of patients with epicardial versus 1% of those with
      transvenous implantations (p = 0.00005, odds ratio 19.4, 95% confidence interval
      2.7 to 86.7). These differences persisted after excluding patients with
      concurrent cardiac surgery. Preoperative occurrence of arrhythmias was the
      strongest independent predictor for postoperative occurrence (p < 0.01 for VT, p
      < 0.0001 for atrial fibrillation). Epicardial implantation (p = 0.03) and a
      history of myocardial infarction (p = 0.04) were independent predictors for
      postoperative VT exacerbation, whereas epicardial implantation (p < 0.05) and
      concurrent coronary bypass surgery (p = 0.0001) were independent predictors for
      postoperative new atrial fibrillation. Perioperative discontinuation of
      antiarrhythmic drugs did not influence postoperative VT exacerbation. Epicardial
      implantation was associated with longer length of hospital stay than transvenous
      implantation (p = 0.0005), independent of age, left ventricular ejection
      fraction, and concurrent cardiac surgery.

PMID- 7810489
TI  - Comparison of echocardiographic variables between type I diabetics and normal
      controls.
AB  - This report compares echocardiographic estimates of systolic and diastolic
      function and ventricular dimensions in type I diabetics and normal controls. A
      random sample of 60 diabetics selected from a central hospital diabetic clinic
      was compared with a sample of 40 nondiabetic controls, and matched to the
      diabetics by age, gender, and blood pressure. Simple comparisons showed that
      diabetics had a higher mean resting heart rate (HR) (p < 0.001) and a slower
      diastolic early filling phase (maximal rate of increase in left ventricular
      dimension in early diastole [v/dtmax], p = 0.08; time from end-systole until
      dv/dtmax [ES-dv/dtmax], p = 0.03), which were explained by differences in HR and
      other factors. Resting HR was significantly associated with several
      echocardiographic variables, but the slope relating resting HR to ventricular
      dimension was more negative in diabetics than in controls (end-diastolic
      diameter, p < 0.008; end-systolic diameter, p < 0.005), and the ratio of systolic
      to diastolic duration was significantly (p < 0.01) less positive in diabetics.
      The association of resting HR to duration of isovolumic diastole was positive in
      diabetics and negative in controls (p < 0.02). Among diabetics, those with higher
      resting HR had more retinopathy (p < 0.05), microalbuminuria (p < 0.05), smaller
      ventricles (p < 0.01), and longer isovolumic diastole (p < 0.05). Poorer diabetic
      control was associated with poorer systolic (fractional shortening, p < 0.05) and
      diastolic (dv/dtmax, p < 0.05; ES-dv/dtmax, p < 0.05) function.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7810490
TI  - Role of late potentials in identifying patients at risk for ventricular
      tachycardia after surgical correction of congenital heart disease.
AB  - This study evaluates the role of late potentials in identifying patients with
      sustained ventricular tachycardia (VT) after surgery for congenital heart defects
      using right ventriculotomy. Nine patients with early (1 to 12 months) or late VT
      (spontaneous in 7 [induced during electrophysiologic study in 6 of the 7] and
      induced in 2) and 104 patients without VT were studied. All patients had complete
      right bundle branch block. Late potentials were quantified by 3 time-domain
      parameters of the signal-averaged electrocardiogram: total filtered QRS duration,
      root-mean-square voltage in the last 40 ms, and low-amplitude signal duration of
      the terminal filtered QRS complex. Root-mean-square voltage filtered at 80 to 250
      Hz was lower in patients with than without VT (9 +/- 6 vs 16 +/- 8 microV, p <
      0.01). By multivariate analysis, more complex surgery (i.e., insertion of
      extracardiac conduits, Kawashima operation, etc.), lower root-mean-square
      voltage, and higher Lown grade (2 to 5) of ventricular arrhythmias on routine
      postoperative Holter recordings were the only independent predictors of VT (p <
      0.001, < 0.05, and < 0.05, respectively). A combination of more complex surgery,
      root-mean-square voltage < 14 microV, and Lown grade 2 to 5 ventricular
      arrhythmias was highly predictive of VT (positive predictive value 75%).
      Conversely, patients without complex surgery and with root-mean-square voltage of
      > 13 microV were not likely to develop VT (negative predictive value 100%). Late
      potentials are an independent predictor of VT and may improve the identification
      of patients at low and high risk of VT after surgery for congenital heart defects
      using right ventriculotomy.

PMID- 7810491
TI  - Major cardiac findings at necropsy in 366 American octogenarians.
AB  - We examined the hearts of 366 octogenarians (184 women [50%], 264 white [72%],
      mean age 84 +/- 4 years). The cause of death was cardiac in 195 (53%), noncardiac
      but vascular in 47 (13%), and noncardiac and nonvascular in 124 patients (34%).
      Of the 195 patients with fatal cardiac disease, atherosclerotic coronary artery
      disease was the cause of death in 127 (65%): acute myocardial infarction in 87
      (69%), sudden cardiac arrest outside the hospital in 19 (15%), chronic congestive
      heart failure with healed myocardial infarction in 15 (12%), and complications of
      coronary bypass surgery in 6 (4%). At least 1 of the 4 major (left main, left
      anterior descending, left circumflex, and right) epicardial coronary arteries was
      narrowed > 75% in cross-sectional area by atherosclerotic plaque in 218 patients
      (60%). The mean number of significantly narrowed major epicardial coronary
      arteries was 1.7, 1.3, and 0.7 in those who died of cardiac, peripheral vascular,
      or noncardiovascular causes, respectively. Among the 87 patients (33 men and 54
      women) with fatal acute myocardial infarction, the women more often had ruptured
      ventricles (21 of 54 [39%] vs 3 of 33 [9%]), and fewer women had healed
      myocardial infarcts (11 of 54 [20%] vs 24 of 33 [73%], p < 0.05). Calcific
      deposits were present in the epicardial coronary arteries in 285 patients (78%),
      in the mitral annulus in 140 (38%), and in aortic valve cusps in 153
      (42%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7810492
TI  - Life expectancy in the Marfan syndrome.
AB  - Data reported in 1972 indicated that lifespan in patients with the Marfan
      syndrome is markedly shortened, and that most deaths are cardiovascular. This
      study was performed to determine whether survival in the Marfan syndrome has
      changed since 1972, and to discern whether treatment (medical or surgical) has
      altered prognosis. Survival curves were generated on 417 patients from 4 referral
      centers, with a definite diagnosis of the Marfan syndrome. Birth date, age at
      death, cardiovascular surgery, or treatment with beta blockers, or any
      combination of these, were included in the analysis. Forty-seven of 417 patients
      died. Mean age at death (41 +/- 18 years) was significantly increased compared
      with age in 1972 (32 +/- 16 years, p = 0.0023). Median (50%) cumulative
      probability of survival in 1993 was 72 years compared with 48 years in 1972. Of
      112 surgically treated patients, 10-year probability of survival was 70%.
      Patients undergoing surgery after 1980 enjoyed significantly increased survival
      than patients who had undergone operation before 1980 (p = 0.008). In conclusion,
      life expectancy for patients with the Marfan syndrome has increased > 25% since
      1972. Reasons for this dramatic increase may include (1) an overall improvement
      in population life expectancy, (2) benefits arising from cardiovascular surgery,
      and (3) greater proportion of milder cases due to increased frequency of
      diagnosis. Medical therapy (including beta blockers) was also associated with an
      increase in probable survival.

PMID- 7810493
TI  - Usefulness of a prototype intravascular ultrasound imaging in evaluation of
      aortic dissection and comparison with angiographic study, transesophageal
      echocardiography, computed tomography, and magnetic resonance imaging.
AB  - The aim of this study was to evaluate the accuracy of information obtained with a
      prototype intravascular ultrasound (IVUS) system in chronic aortic dissection by
      comparing results with angiography, transesophageal echocardiography (TEE),
      computed tomography, or magnetic resonance imaging. We assigned 15 patients to
      IVUS imaging after they underwent angiography. The detection rate of the intimal
      flap was 100% in all segments of the aorta, and the detection rate of the intimal
      tear was 0%, 50%, 50%, and 77.8% in the ascending, arch, descending, and
      abdominal aorta, respectively. IVUS demonstrated 100% of the celiac and renal
      arteries, and 80% of the superior mesenteric arteries as well as their relation
      to dissection. It clarified the origin of 12 of 60 main abdominal branches (20%)
      which were not clear on the angiogram. It also determined the distal extent of
      the dissection in all cases. With regard to the size of the vessel, there was a
      good correlation between IVUS and computed tomographic values (r = 0.98, p <
      0.01). No complications occurred in any patient. IVUS accurately demonstrated
      thrombus or spontaneous echo contrast in the false lumen that was confirmed with
      computed tomography or TEE, or both. It was especially useful in evaluating the
      abdominal aorta with regard to determining the size of the vessel, the extent of
      dissection, the relation of the branches to the false lumen, and the detection of
      intimal tears--important information for follow-up of patients and for planning
      surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7810494
TI  - Low yield of transthoracic echocardiography for cardiac source of embolism.
AB  - To test the hypothesis that the yield for a cardiac source of embolism is very
      low using transthoracic echocardiography, we reviewed the echocardiographic
      reports of 1,010 consecutive patients with cerebrovascular accidents who had
      undergone echocardiography to rule out a cardiac source of embolism; risk factor
      information was also available in 493 patients. We also used 325 controls who had
      undergone echocardiography for other reasons during the same period. Each report
      was examined for the presence of predefined findings depending on their
      propensity for causing cerebrovascular accidents via an embolic process. The
      prevalence of a highly probable source of embolism was low in cases (< 3%) and no
      different from controls after adjusting for age and other risk factors. The
      prevalence of a possible cardiac source of embolism was also low (< 5%) and
      similar in cases and controls. The presence of definite or possible thrombus on
      echocardiography resulted in alteration in therapy in only 2% of cases, of whom
      77% had either heart failure, atrial fibrillation, or Q waves on the
      electrocardiogram. We conclude that the yield of highly probable or possible
      cardiac source of embolism in patients with cerebrovascular accidents is very low
      with transthoracic echocardiography, and is no higher than that noted in similar
      patients without cerebrovascular accidents.

PMID- 7810495
TI  - Current use of green dye curves.

PMID- 7810496
TI  - "Rescue" thrombolysis with intracoronary tissue plasminogen activator for failed
      intravenous thrombolysis with streptokinase for acute myocardial infarction.

PMID- 7810497
TI  - Long-term outcome of octogenarians with unstable angina treated conservatively.

PMID- 7810498
TI  - Intravascular ultrasound assessment of the magnitude and mechanism of coronary
      artery and lumen tapering.

PMID- 7810499
TI  - Correlation of reported exercise test results with recommendation for coronary
      angiography in men and women with suspected coronary artery disease.

PMID- 7810500
TI  - Correlation of atrial fibrillation, paroxysmal supraventricular tachycardia, and
      sinus rhythm with incidences of new coronary events in 1,359 patients, mean age
      81 years, with heart disease.

PMID- 7810501
TI  - A cost-effectiveness strategy for transtelephonic arrhythmia monitoring.

PMID- 7810502
TI  - Mitral valve prolapse in patients with paroxysmal supraventricular tachycardia.

PMID- 7810503
TI  - Cerebral microembolism detected by transcranial Doppler during percutaneous
      transvenous mitral commissurotomy.

PMID- 7810505
TI  - 5-Fluorouracil cardiotoxicity with left ventricular dysfunction under different
      dosing regimens.

PMID- 7810504
TI  - Usefulness of dobutamine echocardiography in distinguishing severe from nonsevere
      valvular aortic stenosis in patients with depressed left ventricular function and
      low transvalvular gradients.

PMID- 7810506
TI  - Pulmonary vasodilatory effects of 12 and 60 parts per million inhaled nitric
      oxide in children with ventricular septal defect.

PMID- 7810507
TI  - Oximetric versus indicator dilution techniques for quantitating intracardiac left
      to-right shunting in adults.

PMID- 7810508
TI  - Left ventricular mass and diastolic filling patterns in quadriplegia and
      implications for effects of normal aging on the heart.

PMID- 7810509
TI  - Left atrial appendage systolic forward flow.

PMID- 7810510
TI  - Systolic and diastolic effects of beta-adrenergic stimulation in normal humans.

PMID- 7810511
TI  - Reversal of primary hyperoxaluria cardiomyopathy after combined liver and renal
      transplantation.

PMID- 7810512
TI  - Chest x-ray and electrocardiographic abnormality after permanent pacemaker
      insertion.

PMID- 7810513
TI  - The risk of life-threatening cardiovascular events with terfenadine.

PMID- 7810514
TI  - Progress report: The AJKD matures.

PMID- 7810515
TI  - Report on a workshop to develop management recommendations for the prevention of
      progression in chronic renal disease.

PMID- 7810517
TI  - Comparability of the different registries on renal replacement therapy.
AB  - This symposium was organized in Milano, Italy, on the occasion of the 25th
      advanced course of the San Carlo Hospital, to discuss and compare the various
      registries of renal replacement therapy throughout the world. Such comparison is
      difficult due to differences in (1) the structure and database of the registries,
      (2) the genetic background and demography of the populations studied, and (3) the
      health care systems of the countries in which the registries are operating.
      Therefore, the presentation of the data at the symposium and in the following
      reports was planned according to a common format, since the speakers were asked
      to answer a series of specific questions focused on the three above-mentioned
      problems. The data reported in all the following papers for the various countries
      are summarized in nine tables in this introductory review. Comparison of the data
      shows that the quantity and quality of renal replacement therapy is variable and
      depends to a considerable extent on the different political and socioeconomic
      backgrounds, with the consequent differences in the health care systems, existing
      in the various countries.

PMID- 7810516
TI  - Screening and management of microalbuminuria in patients with diabetes mellitus:
      recommendations to the Scientific Advisory Board of the National Kidney
      Foundation from an ad hoc committee of the Council on Diabetes Mellitus of the
      National Kidney Foundation.
AB  - All individuals with diabetes mellitus should be screened yearly with a spot
      urine albumin:creatinine ratio to identify those who are at increased risk for
      the development of complications of diabetes mellitus, including nephropathy,
      retinopathy, and cardiovascular disease. Once these high-risk individuals are
      appropriately identified, it is recommended that therapy with an angiotensin
      converting enzyme (ACE) inhibitor be initiated. In addition, cardiovascular risk
      factors should be investigated, and when appropriate, therapeutic interventions
      should be initiated according to existing recommendations.

PMID- 7810518
TI  - Renal replacement therapy in the United States: data from the United States Renal
      Data System.
AB  - This report is a summary of the discussion on the United States Renal Data System
      and its data contents, as presented at the Symposium on World Renal Registries on
      December 10, 1993. The United States Rental Data System is a national database
      that collects and analyzes information on the incidence, prevalence, morbidity,
      and mortality, as well as the modalities of therapy of patients with end-stage
      renal disease (ESRD) in the United States. The database is funded by the National
      Institute of Diabetes and Digestive and Kidney Diseases of the National
      Institutes of Health. Data on the patients are provided by the Health Care
      Financing Administration Medicare Program. The coordinating center for the
      database, operated through a contract mechanism, was formerly at the Urban
      Institute in Washington, DC, but is currently located at the University of
      Michigan, Ann Arbor, MI. The data system contains information on over 462,000
      patients with more than 4 million dialysis records, 2.3 million inpatient
      records, 94,000 transplant reports, and more than 290,000 follow-up reports. The
      incidence rate of ESRD is approximately 180 per million population. However, the
      rate is higher in African-Americans (430) and Native Americans (281) than in
      whites (153) and Asian/Pacific Islanders (133). The gross mortality rate of the
      entire ESRD population is approximately 168 deaths per 1,000 patient-years at
      risk. The death rate is higher in diabetic than in nondiabetic ESRD patients. It
      is also higher in ESRD patients older than 65 years (357) than in patients in the
      45- to 64-year-old age group (158) or those in the 20- to 44-year-old age group
      (62).

PMID- 7810519
TI  - Renal replacement therapy in Canada: a report from the Canadian Organ Replacement
      Register.
AB  - We report here the demography and results of renal replacement therapy in Canada
      from 1981 to 1992. The new case rate for patients entering renal replacement
      therapy programs in Canada has increased dramatically over the last 12 years,
      from 49.9 per million to 98.4 per million of the population. The largest
      increases have been among the elderly, from 146.2 per million in 1981 to 381.9
      per million in 1992 for those aged 65 to 74 years. There has been an even more
      dramatic increase for those over 75 years, from 83.6 per million in 1981 to 261.6
      per million in 1992. There has been a similar increase in the prevalence rate,
      with an increase from 229.1 per million in 1981 to 518.5 per million in 1992. The
      hemodialysis rate for 1992 was 172.2 per million and that for peritoneal dialysis
      was 103.1 per million of the population. The renal transplantation rate also
      increased from 20 per million in 1981 to 34.8 per million in 1988, but
      unfortunately has decreased to 27.5 per million in 1992. Diabetes is now the most
      common primary renal diagnosis, having increased from 15% in 1981 to 24% in 1992.
      The 5-year survival rate of all patients on renal replacement therapy was 55%.
      For nondiabetic patients, the 5-year survival rate ranged from 85% for the those
      aged 15 to 44 years to 20% for those over 65 years. Among diabetic patients, the
      5-year survival rate declined from 58% for the 15 to 44 year age group to 10% for
      those over 65 years.

PMID- 7810520
TI  - Current status of renal replacement therapy in Japan.
AB  - The study of the current status of renal replacement therapy in Japan is based on
      the analysis of data from the registry reports for regular dialysis therapy and
      kidney transplantation. The total number of patients receiving regular dialysis
      therapy was 123,926 at the end of 1992: 117,809 (95.1%) on hemodialysis and 6,117
      (4.9%) on peritoneal dialysis. The primary diseases of newly accepted patients
      were chronic glomerulonephritis (42.2%), diabetic nephropathy (28.4%),
      nephrosclerosis (5.9%), polycystic kidney disease (2.7%), chronic pyelonephritis
      (1.6%), and others. The number of kidney transplant patients in Japan was 8,384
      at the end of 1991: 6,154 (73.4%) received a living donor transplantation and
      2,230 (26.9%) received a cadaver donor transplantation. Overall 5-year survival
      rates of dialysis patients were 60.4%: 69.7% for chronic glomerulonephritis,
      41.7% for diabetic nephropathy, 39.6% for nephrosclerosis, 73.6% for diffuse
      polycystic kidney disease, and 66.6% for chronic pyelonephritis. The causes of
      death of dialysis patients were heart failure (31.1%), cerebrovascular accident
      (13.6%), infectious diseases (11.3%), malignancies (7.1%), cachexia/uremia
      (6.7%), myocardial infarction (5.8%), and others. The gross mortality rate of
      dialysis patients was increased in cases of less than 4 hours of the average
      length of each dialysis session, less than 4% and more than 9% of the average
      weight loss during each dialysis session, less than 1.0 of Kt/V, and less than
      0.9 and more than 1.7 g/kg/d of protein catabolic rate. Overall 5-year patient
      and graft survival rates of kidney transplant patients since 1964 were 82.7% and
      60.3%: 84.4% and 65.0% in living donor cases, and 77.4% and 46.2% in cadaver
      donor case, respectively. Those since 1983 were 90.1% and 68.2%: 91.3% and 72.6%
      in living donor cases, and 87.8% and 59.3%, respectively. Graft survival rates
      were superior in cases treated with combined steroid, cyclosporine and
      azathioprine or mizoribine, to those treated with other immuno-suppressive
      regimens, and they decreased as the number of HLA-A, -B and -DR increased.

PMID- 7810521
TI  - Demography and survival of patients receiving treatment for chronic renal failure
      in Australia and New Zealand: report on dialysis and renal transplantation
      treatment from the Australia and New Zealand Dialysis and Transplant Registry.
AB  - There were 7,059 (403 per million) Australian patients and 1,341 (388 per
      million) New Zealand patients receiving renal replacement treatment at the end of
      1992. Fifty-three percent and 50%, respectively, were dependent on a functioning
      transplant, 87% and 80%, respectively, from a cadaver donor. In Australia the
      majority of dialysis patients depended on hemodialysis (68%) and continuous
      ambulatory peritoneal dialysis (CAPD) (31%); 68% of patients were dialysing at
      home or in a satellite (free-standing) facility. The majority (62%) of home
      dialysis patients used CAPD treatment. In New Zealand there were 44% of patients
      on hemodialysis; 83% dialyzed at home and the majority (65%) used CAPD treatment.
      Few dialysis units (five of 71) in Australia were "for-profit" facilities; there
      was none in New Zealand. Universal health care has been available for renal
      replacement treatment for 20 years. The annual incidence of new patients
      increased steadily during the past 10 years, to 61 per million (Australia) and 69
      per million (New Zealand) in 1992. There were disproportionate numbers of
      indigenous Australian Aboriginals (51%), New Zealand Maoris (30%), and Polynesian
      Pacific Islanders (11%) compared with their distribution in the general
      population. There was a considerable increase in elderly and diabetic patients
      during the period from 1983 to 1992: in Australia, 25% of patients were over 65
      years of age and 14% of patients were diabetic, and in New Zealand, 16% of
      patients were over 65 years of age and 25% of patients were diabetic. The renal
      transplantation rate has remained unchanged since 1983 at 27 per million in
      Australia, but has increased markedly from 20 to 33 per million in New Zealand.
      The annual transplantation rate was 20% to 30% of those patients aged 15 to 64
      years who were likely to be transplanted. The multifactorial analysis of risk
      factors for survival of dialysis patients showed age, male gender, CAPD
      treatment, Aboriginal race, and diabetic or analgesic nephropathy to be
      associated with lower rates of survival. Deaths were commonly due to a cardiac
      cause (43%), mostly myocardial infarction, or to infection (17%) or withdrawal
      from treatment (14%). The overall death rate was 12% of patients at risk in 1992.
      Multifactorial analysis of risk factors for graft survival in transplanted
      patients showed patient age, diabetic nephropathy, donor age, single-drug
      regimen, and low transplant activity (operations) at a center to be associated
      with lower rates of survival.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7810522
TI  - Continuous venovenous hemodiafiltration in infants and children.
AB  - Continuous venovenous hemodiafiltration (CVVHD) is not commonly used in pediatric
      intensive care units due to the lack of suitable equipment needed for this
      technique of renal replacement therapy (RRT). We have used an adapted
      hemodialysis machine that includes a blood pump controller, an air leak detector,
      and a venous pressure monitor over the past year in the pediatric intensive care
      unit. Blood lines available for hemodialysis were used for CVVHD, limiting the
      extracorporeal circuit volume to 38 mL, which allows for CVVHD capability in an
      infant as small as 4.5 kg without a blood-primed circuit. We have compared this
      experience to previous continuous arteriovenous hemodiafiltration (CAVHD) at our
      institution. The two groups (CVVHD and CAVHD) were similar in age, weight, blood
      pressure, and indication for RRT. There was significantly less number of
      hemofilters used, an improved number of hours per hemofilter, and a significantly
      less change of RRT modality due to ineffective dialysis (CVVHD 0% v CAVHD 32%)
      when using CVVHD. Furthermore, an average of 48% less heparin was used in the
      CVVHD population. We conclude that CVVHD can be safely and effectively carried
      out in infants and small children with less heparinization, no need for arterial
      access, and less risk of ineffective RRT.

PMID- 7810523
TI  - The European (European Dialysis and Transplantation Association-European Renal
      Association) Registry.
AB  - The European Dialysis and Transplantation Association-European Renal Association
      (EDTA-ERA) Registry, now some 30 years old, has collected data throughout Europe
      since its inception and now covers nearly 700 million people in some 36
      countries. Approximately 2,000 centers report to it. It has been possible to
      follow the way in which treatment for renal failure has developed in Europe, and
      this has not always been uniform. The nature of the treatment offered, the
      survival of patients on treatment, and sequentially many areas of their
      management have been addressed and reported. The Registry continues to work both
      in the field of end-stage renal failure and other fields of renal disease. It is
      assisting in the development of national registries and subnational renal
      registries throughout Europe. The multinational, multicultural nature of its area
      of interests makes this Registry a uniquely placed source to study many aspects
      of the management of patients with renal disease and of contributing to their
      care in the variety of healthcare system that exist in Europe and in the
      countries bordering the Mediterranean.

PMID- 7810524
TI  - Renal replacement therapy for end-stage renal failure in France: current status
      and evolutive trends over the last decade.
AB  - Between 1982 and 1992, the number of new patients taken yearly onto renal
      replacement therapy (RRT) increased from 42 to 62 per million population. By
      December 1992, approximately 22,800 patients (401 per million population) were
      alive under some mode of RRT. The number of patients aged 15 to 34 years starting
      RRT slumped from 20% to 11%, whereas that of patients aged > or = 75 years
      tripled (5% to 15%). The proportion of patients with primary glomerulopathy
      decreased (25% to 19%) whereas that of patients with vascular diseases or
      diabetic nephropathy increased notably (14% to 21% and 7% to 13%, respectively).
      An ever increasing proportion of patients were treated with in-center or limited
      care hemodialysis, whereas home hemodialysis steadily declined and continuous
      ambulatory peritoneal dialysis (CAPD) was applied to 7% of patients in 1991. The
      average number of weekly hemodialysis hours tended to decrease, particularly for
      patients aged > or = 75 years. At best, in 1991, approximately 2,000 renal
      transplants (36 per million population) were performed yearly, but unfortunately,
      this figure is steadily declining. Five- and 10-year overall survival rates were
      similar in young patients who were treated with center or home hemodialysis and
      those who underwent transplantation. Overall survival is rather poor in diabetic
      patients, 38% and 17% at 5 and 10 years, respectively, but best in those with a
      functioning first kidney transplant (69% at 10 years). Cardiac causes accounted
      for one third of all deaths in hemodialysis patients, vascular causes for 15% to
      18%, and infectious causes for 10%. Deaths of cardiac or infectious origin were
      highest in diabetic patients when compared with those recorded in patients with
      standard (nonsystemic) and vascular renal diseases.

PMID- 7810525
TI  - 1983 to 1992: report on regular dialysis and transplantation in Lombardy.
AB  - This 1993 report of the Lombardy Regional Dialysis and Transplant Registry refers
      to all the data collected between January 1, 1983, and December, 31, 1992, by
      means of individual patient questionnaires sent to all of Lombardy's 44 renal
      units (100% replies). The number of patients recorded by the Registry as being
      alive progressively increased; by the end of 1992, the number was 6,014 (655
      patients per million population): 4,770 patients were on dialysis treatment (515
      patients per million population, 79.3%) and 1,244 patients (140 patients per
      million population, 20.7%) had received a kidney graft. The acceptance rate for
      dialysis increased from 64 per million population in 1983 to 102 per million
      population in 1992; the increase in the transplant rate was much lower (from 18.7
      to 21.3 per million population). The percentage of primary nephropathies in the
      new patients accepted for dialysis treatment were 22.0% glomerulonephritis, 13.8%
      interstitial nephritis, 15.2% vascular diseases, 10.1% cystic kidney, and 10.6%
      diabetes. The use of acetate hemodialysis declined over the 10-year period from
      72.4% to 17.5%; that of bicarbonate hemodialysis increased from 8.8% to 50.1% and
      that of hemodiafiltration increased from 0.2% to 11.1%. The prevalence of
      hospital hemodialysis was stable, ranging from 55.4% to 52.2%; home hemodialysis
      decreased from 15.7% to 5.3%, continuous ambulatory peritoneal dialysis increased
      from 13.3% to 19.6%, and limited care increased from 13.7% to 22.4%. The crude
      death rate increased from 7.5% in 1983 to 10.5% in 1992. The survival rate
      (Kaplan-Meier) of all patients on dialysis was 78.8% at 2 years, 62.2% at 4
      years, and 40% at 8 years; for transplanted patients, the survival and graft
      survival rate at 2 years was, respectively, 95% and 86%. The relative death risk
      of the patients on peritoneal dialysis with respect to those on hemodialysis was
      1.419, as estimated by the Cox proportional hazard regression model. The main
      causes of deaths of patients on dialysis treatment during the year 1992 were
      cardiovascular diseases (47.0%) and cachexia (19.5%); in transplanted patients,
      they were cardiovascular diseases (36.6%) and infections (34%). Registries are
      not only important for planning health care but are also very useful instruments
      for clinical research.

PMID- 7810526
TI  - Study of vascular access blood flow by angiodynography.
AB  - Angiodynography has been recommended as a safe and accurate way to determine the
      blood flow through hemodialysis vascular grafts. This information might be used
      prophylactically to avert total graft occlusion. We examined the blood flows
      obtained by this technique after an interval of 6 months in a group of
      hemodialysis patients whose grafts did not require surgical or radiologic
      manipulation in the interim. No changes in the mean blood flows were noted during
      the period of observation. Although a significant correlation was found between
      the original and follow-up blood flows, the coefficient of determination was only
      0.27. The Bland-Altman plot of these data showed that both large decreases and
      increases in graft flows were recorded for many patients whose graft function did
      not appear to worsen. Dialysis itself did not seem to alter the measured blood
      flow. We conclude that caution must be used in interpreting changes in blood flow
      measured over time by angiodynography. More study of the factors accounting for
      the variability in blood flow estimations by this technique are needed.

PMID- 7810527
TI  - Hemodialysis urea rebound: the effect of increasing dialysis efficiency.
AB  - Urea rebound has been documented to occur after hemodialysis, but the magnitude
      and causes are not clearly defined. In this study we evaluated the effect of high
      flux hemodialysis on urea rebound and Kt/V. Blood urea nitrogen samples were
      obtained before, immediately after, and 30 minutes after hemodialysis in 49
      patients. Rebound was evaluated with respect to dialysis efficiency, dialysis
      treatment time, the occurrence of hypotension, and hematocrit. Urea rebound was
      significant and resulted in an overall decrease in Kt/V from 1.2 +/- 0.3 to 1.0
      +/- 0.2 (P < 0.001). Of the 45 patients with a measured Kt/V of greater than 1.0,
      40% had an actual delivered Kt/V of less than 1.0 once rebound was taken into
      account. Urea rebound correlated strongly with dialysis efficiency but not with
      hypotension, suggesting that rebound resulted primarily from delayed urea mass
      transfer across cell membranes. We conclude that increasing dialysis efficiency
      increases urea rebound and increases the error in Kt/V determinations from single
      pool urea kinetics.

PMID- 7810528
TI  - Hepatitis C virus: the nephrologist's view.
AB  - The last 4 years have been a period of rapid expansion in our understanding of
      both the molecular biology and clinical significance of hepatitis C virus (HCV)
      infection. Initial studies using first-generation enzyme-linked immunosorbent
      assays suggested that the end-stage renal disease population had an exceptionally
      high prevalence of anti-HCV compared with asymptomatic healthy blood donors.
      Subsequent analyses with second-generation assays and polymerase chain reaction
      techniques to detect viremia confirmed these earlier studies. Considering the
      prevalence of HCV within the dialysis population, it comes as no surprise that
      several studies confirmed HCV as the leading cause of non-A, non-B hepatitis
      among renal allograft recipients. Furthermore, transmission of HCV by
      transplantation of a kidney from an HCV-infected organ donor has been
      unequivocally demonstrated. The natural history of HCV infection in the
      immunosuppressed allograft recipient and its impact on long-term patient outcome
      are still being analyzed. Finally, HCV has been associated with essential mixed
      cryoglobulinemia and several histologic patterns of immune complex
      glomerulonephritis, including membranous and membrano-proliferative
      glomerulonephritis. Although HCV antigen-antibody complexes have not been
      demonstrated in the kidney, the marked decrease in proteinuria following
      clearance of HCV RNA with interferon alpha-2b therapy suggests an etiologic role
      for HCV in these glomerular diseases. Furthermore, the demonstration of HCV RNA
      in the cryoprecipitate of patients with essential mixed cryoglobulinemia and a
      beneficial response to treatment with interferon alpha-2b also suggest a role for
      HCV in the pathogenesis of these clinical syndromes.

PMID- 7810529
TI  - Efficiency of three different hemodialysis membranes for plasma porphyrin
      removal.
AB  - To assess the capability of three different membranes to remove porphyrins,
      plasma and dialysate porphyrin levels were fluorometrically measured in 10
      patients with end-stage renal failure who were on hemodialysis. Three different
      hemodialysis membranes were used: cuprophan, polyacrylonitrile, and cellulose
      triacetate. Total plasma porphyrin concentrations decreased after dialysis, but
      to a lesser extent when using the cuprophan membrane (19%) than with the
      polyacrylonitrile (26%) or cellulose triacetate (30%) membranes (P < 0.01).
      However, since the free plasma porphyrin fraction remained unchanged, it can be
      assumed that the equilibrium between protein-bound and non-protein-bound (free)
      porphyrins is displaced toward the latter fraction. Dialysate porphyrin levels
      were lower (P < 0.01) when using the cuprophan membrane (10.1 micrograms/session)
      than when using polyacrylonitrile (17.8 micrograms/session) and cellulose
      triacetate (21.9 micrograms/session). Although most of the plasma porphyrins are
      protein bound, our results show that hemodialysis can remove significant amounts
      of non-protein-bound (free) porphyrins. The polyacrylonitrile and cellulose
      triacetate membranes had a greater capacity for porphyrin removal than cuprophan.
      Thus, two high-permeability membranes (polyacrylonitrile and cellulose
      triacetate) should be used whenever a reduction of plasma porphyrin levels is
      desired.

PMID- 7810530
TI  - Ankle-arm blood pressure index as a marker for atherosclerotic vascular diseases
      in hemodialysis patients.
AB  - The ankle to arm blood pressure index (AABI) has been recently found to be a
      strong predictor of cardiovascular and overall mortality in several populations.
      The test, which is a noninvasive marker for lower extremity vascular disease
      (when the index is < 0.9), is an office procedure that is simple to perform. The
      purpose of this study was to evaluate the AABI in hemodialysis patients. One
      hundred seventy-seven hemodialysis patients were studied, of which the AABI could
      be measured in 142. The AABI was then compared in patients with and without
      coronary artery disease, cerebrovascular disease, and peripheral vascular
      disease. In patients with or without coronary artery disease, the AABI was,
      respectively, 0.87 +/- 0.03 and 1.03 +/- 0.02 (P < 0.0001). For cerebrovascular
      disease, the mean AABI for patients with or without disease was, respectively,
      0.82 +/- 0.04 and 1.00 +/- 0.02 (P < 0.0004). In patients with or without
      peripheral vascular disease, the mean AABI was, respectively, 0.75 +/- 0.04 and
      1.02 +/- 0.02 (P < 0.0001). The mean AABI was 0.86 +/- 0.03 in patients with any
      of the three diseases compared with 1.07 +/- 0.02 in patients without any
      vascular disease (P < 0.0001). Thirty-eight percent of patients had an AABI of
      less than 0.9; 24% were less than 0.8 and 11% were less than 0.7.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7810531
TI  - Interferon-alpha facilitates renal transplantation in hemodialysis patients with
      chronic viral hepatitis.
AB  - Interferon-alpha has not been used previously in hemodialysis patients with
      chronic hepatitis B and C. This uncontrolled report evaluates the biochemical
      and/or histologic profile resulting from the administration of interferon-alpha
      in seven hemodialysis patients, two with chronic hepatitis B and five with
      hepatitis C. Biochemical improvement was noted in all patients. Histologic
      progression did not occur in the two cases in which such assessment was made, and
      five of them were subsequently transplanted without recurrence of disease.

PMID- 7810532
TI  - Intrarenal extramedullary erythropoiesis in renal allograft fine-needle
      aspirates.
AB  - Recombinant human erythropoietin (rhEPO) is widely used in patients with end
      stage renal disease and occasionally in renal allograft recipients to correct
      anemia. Red blood cell production is markedly increased by rhEPO; however, no
      extramedullary erythropoiesis (EME) has been associated with this hormone. We
      observed intrarenal EME in five allograft fine-needle aspirates performed for
      reduced graft function in four patients between 3.7 and 7 weeks following
      transplantation. These four patients received rhEPO during dialysis and three
      resumed rhEPO therapy after transplantation; all four remained anemic. Donors
      were between 13 months and 13 years of age, with one pediatric and three adult
      recipients. Aspirates with apparently incidental EME contained all stages of red
      blood cell precursors, but these cells were not observed in corresponding
      peripheral blood samples. The hematopoietic cells could be readily distinguished
      from cells of lymphoid origin. There were no correlations between intragraft EME
      and aspirate or clinical diagnosis referable to renal dysfunction. Aspirates
      performed prior to 3.7 weeks or after 7 weeks did not demonstrate EME. These data
      suggest that endogenous EPO and rhEPO in anemic patients receiving pediatric
      renal allografts may activate red blood cell precursors in the young graft,
      inducing intrarenal EME. Recognition of this entity is important to distinguish
      it from immune activation or malignancy within the donor organ.

PMID- 7810533
TI  - Antioxidants attenuate endotoxin-induced acute renal failure in rats.
AB  - Acute kidney dysfunction, manifested by a reduction in renal blood flow and in
      the glomerular filtration rate, is a common finding in septic shock. The
      pathogenetic mechanisms responsible for the renal dysfunction observed in the
      endotoxemic murine model are not completely understood. In this study, an attempt
      was made to halt the progressive renal dysfunction in the rats by administration
      of the antioxidants dimethylthiourea (DMTU) (50 mg/100 g) and superoxide
      dismutase (SOD) (0.4 mg/100 g) before endotoxin infusion (0.5 mg/100 g), or by
      inducing endotoxin tolerance. Renal function, assessed by creatinine, inulin, and
      p-aminohippuric acid clearance, nicotinamide adenine dinucleotide, and
      electrolyte reabsorption, was measured 4 hours after the endotoxin infusion.
      Renal function declined in all rats throughout the study period. However, the
      reduction in renal function was markedly slower in endotoxemic rats administered
      DMTU and SOD compared with untreated rats. Similar results were found following
      induction of endotoxin tolerance. These data suggest that DMTU, SOD, and
      endotoxin tolerance may be potentially beneficial in halting progressive renal
      damage associated with endotoxemia.

PMID- 7810534
TI  - Arginine vasopressin gene expression in rats with puromycin-induced nephrotic
      syndrome.
AB  - Nephrotic syndrome is characterized by water and sodium retention, which leads to
      edema formation. The nonosmotic stimulation of arginine vasopressin (AVP) release
      from the pituitary gland has been implicated to be one of the important factors
      of abnormal water retention in patients with nephrotic syndrome. It is not known,
      however, whether nephrotic syndrome is associated with stimulation of
      hypothalamic vasopressin gene expression. Puromycin aminonucleoside is known to
      cause altered glomerular permeability, which results in experimental nephrotic
      syndrome in rats. In the present study, therefore, AVP gene expression has been
      studied in the hypothalamus of rats with puromycin aminonucleoside-induced
      nephrotic syndrome (PNS). Nephrotic syndrome was induced by a single intravenous
      injection of puromycin aminonucleoside (50 mg/kg body weight). Nephrotic syndrome
      was confirmed by urinary protein excretion (control 20.8 +/- 3.5 mg/24 hr v PNS
      273.9 +/- 41.4 mg/24 hr; P < 0.0001, n = 6) and serum albumin concentrations
      (control 4.52 +/- 0.07 g/dL v PNS 2.96 +/- 0.22 g/dL; P < 0.001, n = 6). In PNS
      rats, plasma AVP was significantly higher than in control rats (control 0.77 +/-
      0.10 pg/mL v PNS 2.13 +/- 0.42 pg/mL; P < 0.005, n = 12), even though there were
      no differences in plasma osmolality (control 292.0 +/- 2.0 mOsm/kg H2O v PNS
      290.3 +/- 2.5 mOsm/kg H2O; P = NS, n = 12) or serum sodium concentration (control
      142.7 +/- 0.7 v PNS 142.1 +/- 1.1; PNS, n = 12).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7810535
TI  - Djenkol bean poisoning (djenkolism): an unusual cause of acute renal failure.
AB  - This report describes a patient with acute renal failure that resulted from the
      ingestion of djenkol beans. Features of acute djenkolism include nausea,
      vomiting, bilateral loin pain, gross hematuria, and oliguria. The blood urea
      level was 16.2 mmol/L and the serum creatinine was 460 mumol/L. Phase contrast
      microscopy of the urinary sediment indicated that the hematuria was
      nonglomerular. Ultrasound of the kidneys showed slightly enlarged kidneys with no
      features of obstruction. Renal biopsy showed acute tubular necrosis similar to
      the single animal study reported in the literature. With conservative therapy,
      which included rehydration with normal saline and alkalinization of the urine
      with sodium bicarbonate, the acute renal failure resolved. Based on its
      chemistry, djenkol bean-associated acute renal failure may be analogous to acute
      uric acid nephropathy.

PMID- 7810536
TI  - Membranoproliferative glomerulonephritis associated with hepatitis C virus
      infection responsive to interferon-alpha.
AB  - A 42-year-old man with hepatitis C virus infection, cryoglobulinemia,
      hypocomplementemia, and nephrotic syndrome is reported. The kidney biopsy showed
      membranoproliferative glomerulonephritis. The patient was treated with interferon
      alpha for 2 months. After the treatment, serum hepatitis C virus RNA became
      negative and nephrotic syndrome remitted. Repeat biopsy of the kidney revealed an
      improvement in renal histology. This case confirms an association between
      hepatitis C virus infection and membranoproliferative glomerulonephritis and the
      usefulness of interferon-alpha for treatment.

PMID- 7810539
TI  - Occurrence of respiratory alkalosis in continuous ambulatory peritoneal dialysis
      patients with pulmonary disease.
AB  - Continuous ambulatory peritoneal dialysis (CAPD) patients are prone to develop
      respiratory alkalosis when hypoxemia occurs secondary to pulmonary problems. This
      is due to "fixed" bicarbonate levels that do not allow for an unlimited degree of
      hyperventilation. Recognition of this problem is important because treatment with
      oxygen or acidification with ammonium chloride is effective in avoiding severe
      alkalemia in these patients.

PMID- 7810537
TI  - Spontaneous vertebral artery dissection as a complication of autosomal dominant
      polycystic kidney disease.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) may be associated with a
      variety of cardiovascular complications, including intracranial saccular
      aneurysms. In ADPKD, intracranial saccular aneurysms tend to rupture more
      frequently and earlier than the sporadic variety with a tendency to cluster in
      families. In contrast, dissecting intracranial aneurysms are rarely associated
      with either intracranial saccular aneurysms or ADPKD. We describe an ADPKD-1
      patient whose course was complicated by a spontaneous dissection of a vertebral
      artery aneurysm. This particular patient had previously experienced three
      episodes of ascending aortic dissection with cystic medial necrosis. Intracranial
      vascular and aneurysmal dissection may occur in select ADPKD patients with
      familial clusters.

PMID- 7810538
TI  - Recurrence of immunoglobulin A-kappa crystalline deposition disease after kidney
      transplantation.
AB  - Cases of immunoglobulin A heavy chain and kappa light chain deposition disease
      are rare and their clinical presentations vary. We report one patient with
      histopathologic and clinical findings of a microangiopathic glomerulonephritis
      due to immunoglobulin A-kappa deposition. Ultrastructural studies revealed highly
      ordered deposits in the capillary lumen, mesangium, and basement membrane. The
      disease recurred at 2.5 years after a cadaveric kidney transplantation. Pulse
      steroid therapy was repeatedly effective in retarding further progression of
      renal deterioration in this patient.

PMID- 7810540
TI  - Angiotensin-converting enzyme inhibitors may cause renal dysfunction in patients
      on long-term lithium treatment.
AB  - Anecdotal observations suggest that renal dysfunction may occur when unadjusted
      doses of angiotensin-converting enzyme inhibitors are administered to patients on
      long-term lithium treatment. Although no systematic experimental studies or
      controlled clinical observations are available, lithium is known to activate the
      renin angiotensin system through several mechanisms. In addition, direct
      interactions between lithium and angiotensin II may take place on a cellular
      level. We propose that (1) renal function should be closely monitored when
      patients on lithium treatment are given angiotensin-converting enzyme inhibitors
      and that (2) doses of both drugs should be chosen with caution to avoid serious
      drug interaction.

PMID- 7810541
TI  - Nephrotic syndrome in a patient with unilateral renal dysplasia.

PMID- 7810542
TI  - Is parenteral nutrition therapy of value in acute renal failure patients?
AB  - A patient with oliguric acute renal failure (ARF) following mitral valve surgery
      is presented. The patient was treated with parenteral nutrition and hemodialysis.
      While the patient survived, there were several complications of nutrition
      therapy. In this review, the benefits, risks, and uncertainties regarding
      parenteral nutrition in ARF are considered. First, the differences in metabolism
      in complicated and uncomplicated acute uremia are discussed. The important roles
      of alterations in intermediary metabolism and of proteases in the catabolism of
      ARF are emphasized. The historical basis of parenteral nutrition treatment in ARF
      is reviewed. The results are divided regarding the relationship among nutritional
      support, improvement in renal function, and enhanced patient survival. A critical
      analysis of nitrogen metabolism results reported in the literature does not
      convincingly support the effectiveness of parenteral nutrition formulae in
      generating positive nitrogen balance. The complications of parenteral nutrition
      therapy are outlined. In light of the uncertain efficacy and recognized risks of
      prolonged parenteral nutrition, a rationale for approaching therapy is presented
      that is based on the estimated metabolic stress and protein-energy requirements
      of the individual ARF patient.

PMID- 7810543
TI  - Follow-up study of chrysotile asbestos textile workers: cohort mortality and case
      control analyses.
AB  - Previous studies of mortality among white males employed in a Charleston, South
      Carolina asbestos textile plant using chrysotile demonstrated significant excess
      mortality due to asbestos-related disease and a steep exposure-response
      relationship for lung cancer. This cohort was further studied by adding 15 years
      of follow-up and including mortality among white female and black male workers.
      Nested case-control analyses were undertaken to further explore possible
      differences in lung cancer risk by textile operation as well as possible
      confounding by mineral oil exposures. Preliminary data for white males have been
      previously published. White males experienced statistically significant excess
      mortality due to lung cancer (standardized mortality ratio [SMR] = 2.30;
      confidence interval [CI] = 1.88-2.79), all causes (SMR = 1.48; CI = 1.38-158),
      all cancers (SMR = 1.50; CI = 1.29-1.72), diabetes mellitus (SMR = 2.05; CI =
      1.18-3.33), heart disease (SMR = 1.41; CI = 1.26-1.58), cerebrovascular disease
      (SMR = 1.50; CI = 1.08-2.02), pneumoconiosis and other respiratory diseases (SMR
      = 4.10; CI = 3.10-5.31), and accidents (SMR = 1.49; CI = 1.15-1.91). Among white
      females, statistically significant excesses occurred for lung cancer (SMR = 2.75;
      CI = 2.06-3.61), all causes (SMR = 1.21; CI = 1.11-1.32), pneumoconiosis and
      other respiratory diseases (SMR = 2.40; CI = 1.53-3.60), and other respiratory
      cancers (SMR = 14.98; CI = 4.08-38.7). Among the total cohort of black males, the
      only statistically significant excess observed was for pneumoconiosis (SMR =
      2.19; CI = 1.23-3.62). Based on historical exposure measurements at the plant,
      there was a positive exposure-response relationship for both lung cancer and
      pneumoconiosis. Data for the entire cohort demonstrate an increase in the lung
      cancer relative risk of 2-3% for each fiber/cc-year of cumulative chrysotile
      exposure. This relationship was more consistent for the white male workers. The
      excess risk for lung cancer among white males and females appeared to occur at
      cumulative exposures lower than those for black males. Possible reasons for the
      lesser lung cancer risk among black males include less smoking and differences in
      airborne fiber characteristics experienced by black males as a result of plant
      job placement patterns. The case-control analysis found employment in preparation
      and carding operations (where most of the black males worked) to be associated
      with a slightly reduced lung cancer risk, although not statistically significant,
      whereas spinning and twisting employment was associated with a statistically
      significant increased lung cancer risk compared to other plant
      operations.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7810544
TI  - Mortality at an automotive stamping and assembly complex.
AB  - Mortality among workers with 2 or more years employment at an automotive stamping
      and assembly complex was analyzed using standardized mortality ratio (SMR),
      proportional mortality ratio (PMR), and mortality odds ratio (MOR) methods. The
      stamping plant all-cause SMR was considerably less than expected (for white men,
      SMR = 0.65, 95% confidence interval [CI] = 0.54, 0.79; for black men, SMR = 0.73,
      95% CI = 0.45, 1.13), indicating a strong "healthy worker effect." However, six
      stomach cancer deaths produced an SMR of 4.4 (95% CI = 1.62, 9.6) and a PMR of
      6.8 (95% CI = 2.5, 15). Based on small numbers of cases, stomach cancer risk
      increased with duration in stamping and tool and die departments where exposures
      included drawing compound and other metalworking fluids. Stamping plant lung
      cancer mortality was elevated among production welders (MOR = 2.7, 95% CI = 1.2,
      6.3), and increased with duration. Welding was performed on sheet metal sometimes
      coated with drawing compound, primer, or epoxy resin adhesive. As was observed
      for the stamping plant, the all-cause SMR for the two assembly plants was
      unusually low (for white men, SMR = 0.64, 95% CI = 0.56, 0.73; for black men, SMR
      = 0.57, 95% CI = 0.43, 0.75). The lung cancer SMR was not elevated but the MOR
      was (MOR = 1.58, 95% CI = 1.1, 2.4) and increased with assembly plant duration
      (MOR = 1.78, 95% CI = 1.02, 3.1, at mean duration of cases). In the assembly
      plants, paint oven stack emissions had been reintroduced into the plant by the
      ventilation system.

PMID- 7810545
TI  - Epidemiological studies of work with video display terminals and adverse
      pregnancy outcomes (1984-1992).
AB  - Many epidemiological studies have investigated the claim that work with video
      display terminals (VDT) is a risk factor during pregnancy. Results have been
      inconsistent, although in the majority of cases the hypothesis was not supported.
      Exposure assessment has been very poor and the statistical power of the studies
      generally low. Overall, the studies indicate that VDT operators are not at
      greater risk than the general population, because very low frequency (VLF)
      magnetic fields do not appear to be a risk factor and extremely low frequency
      (ELF) magnetic field exposure is not significantly greater than that experienced
      in other occupational and residential environments. However, since some studies
      lend support to the hypothesis that ELF magnetic fields may be a risk factor for
      pregnancy outcome, studies of subjects exposed to higher than average ELF fields
      are justified.

PMID- 7810546
TI  - Impairment of color vision among workers exposed to low concentrations of
      styrene.
AB  - A field study was conducted among 21 male workers exposed to styrene of
      concentration below 30 ppm in a fiber-reinforced plastic boat manufacturing
      plant. Twenty-one male workers with similar age groupings, years of education,
      and social and occupational state served as referents. The mean end-of-shift
      urinary mandelic acid (MA) and phenylglycoxylic acid (PGA) for the exposed
      workers were 84 mg/g creatinine and 66 mg/g creatinine, respectively. The
      Lanthony D-15 Hue Desaturated Panel was used to evaluate color discrimination of
      the exposed and referent groups. The results of the test were expressed as total
      color difference score (TCDS). The exposed workers' mean TCDS (a higher score
      denotes poorer color discrimination ability) was significantly (p < 0.0006)
      higher than the referents'. Neurobehavioral tests were also conducted, using the
      World Health Organization's Neurobehavioral Core Test Battery (NCTB). All the
      results of the NCTB were poorer for the exposed than for the referents. However,
      significant differences were observed only for Digit Span, Digit Symbol, and
      Benton Visual Retention tests. These results suggest that low exposure to styrene
      could affect some psychometric performance and may impair color vision.

PMID- 7810547
TI  - Respiratory symptoms and asthma among workers exposed to paper dust: a cohort
      study.
AB  - The aim of the present cohort study was to investigate whether exposure to paper
      dust causes increased risk for respiratory symptoms or asthma. The cohort
      included all workers at a soft paper mill who had worked there for more than 1
      year 1960-1986 (n = 1,697). Randomly selected inhabitants of the mill town (n =
      781) were used as unexposed referents. Both groups were investigated using a
      postal questionnaire. From the paper mill cohort, workers with high cumulative
      exposure (n = 313), with medium cumulative exposure (n = 321), and with low
      cumulative exposure (n = 338) to paper dust were selected. In the 1960s and
      1970s, the dust levels were between 5 and 10 mg/m3. After adjustment for smoking
      and gender, paper dust exposure resulted in elevated prevalence ratios for
      chronic cough, chronic phlegm, wheeze, and breathlessness. The prevalence ratios
      ranged from 1.3 to 2.5. No significantly increased risk of asthma was found among
      the exposed, incidence rate ratio 1.4 (95% confidence interval 0.93-1.8). Among
      the exposed, there was an insignificantly increasing incidence rate ratio, 1.0,
      1.4, 2.1, with increasing cumulative exposure. In conclusion, an increased risk
      for respiratory symptoms was observed among workers exposed to paper dust, but
      the study does not permit any definite conclusions regarding asthma and paper
      dust exposure.

PMID- 7810548
TI  - Dust exposure indices and lung function changes in longshoremen and dock workers.
AB  - A group of Dutch harbor workers involved in loading and unloading bulk products
      from sea vessels such as coal, cokes, and some other products like alumina,
      borax, phosphate ore, and vermiculite was studied. Exposures were characterized
      by personal and environmental monitoring. This information was subsequently used
      to estimate several dust exposure indices and to study relationships with lung
      function variables and respiratory symptoms. Average respirable dust exposure
      levels ranged from 0.3-4.0 mg/m3. Workers involved in unloading products from sea
      vessels were exposed to the highest dust levels. Supervisors and workers with
      tasks in the dock had an intermediate to low exposure. Office workers had the
      lowest exposure to respirable dust. Inhalable dust levels were considerably
      higher and average exposures ranged from 0.3-80 mg/m3. The ranking of
      occupational titles by inhalable dust exposure was almost identical to the rank
      order of respirable dust levels. Workers with higher current and cumulative dust
      exposures tended to have a lower lung function, and only shortness of breath had
      a statistically significant relationship with current and cumulative inhalable
      dust exposure. In general, relationships between lung function and inhalable dust
      levels tended to be somewhat stronger in terms of statistical significance,
      because inhalable dust is an estimate of dust deposition in the upper airways and
      lung function is a measurable parameter of airway obstruction in that region.
      However, the differences with respirable dust were minimal, and variability in
      dust exposure levels was extremely large for this population. It was concluded
      that harbor workers involved in unloading ships containing coal and various kinds
      of ore can be exposed to high dust levels. Relationships between dust exposure
      and lung function illustrate that these exposures are a respiratory hazard. Our
      finding that inhalable dust levels have a somewhat stronger relationship with
      lung function level than respirable dust levels deserves further attention.

PMID- 7810549
TI  - Occupation and stomach cancer in a cohort of Swedish men.
AB  - Using the Cancer-Environment Registry of Sweden, which links the 1960 census
      information on employment with cancer incidence data from 1961-1979, we conducted
      a systematic, population-based assessment of stomach cancer incidence by industry
      and occupation for men in Sweden. Nearly 17,000 stomach cancer cases were
      diagnosed during the 19 years of follow-up. Stomach cancer incidence was elevated
      among miners and quarrymen, farmers and fishermen, and craftsmen and production
      workers. Men who held white collar jobs, including professional and technical,
      administrative and management, clerical, and sales jobs, had a reduction in
      stomach cancer incidence. Examination of specific jobs revealed generally
      elevated rates of stomach cancer among men who may be exposed to dusty work
      environments, such as quarry workers, stone cutters, circular and plane
      operators, construction workers, crane operators, heavy laborers, and shop and
      construction metal workers. These occupational associations mostly were observed
      for stomach cancers of noncardia origin, and no significant associations were
      found with cardia cancers. We had no information on dietary or other potential
      confounding factors and cannot make inferences about the role of occupation per
      se, but the current findings support those of earlier investigations and add to
      the evidence of a small but significant occupational role in stomach
      carcinogenesis.

PMID- 7810550
TI  - Application of two secondary documentary sources to identify the underreporting
      of fatal occupational injuries in Cape Town, South Africa.
AB  - We reviewed 8,502 deaths registered at the Salt River state mortuary, Cape Town
      (medical examiner records) for an 18-month period (1/1/90-6/30/91). When fatal
      occupational injuries located from this data source were matched with the records
      of the occupational safety inspectorate of the Department of Manpower, it was
      found that 28% had not been reported in terms of statutory regulations.
      Unreported deaths accounted for 25% of all fatal occupational injuries in the
      construction industry. None of the fatal occupational injuries in agriculture and
      fishing had been reported. Falls constituted 45% of the unreported fatalities.
      High levels of unreported fatal occupational injury indicate deficiencies in
      current occupational safety surveillance and enforcement in South Africa.

PMID- 7810551
TI  - Nature and incidence of self-reported adolescent work injury in Minnesota.
AB  - Most studies of adolescent work-related injury that have been published to date
      have been confined to administratively collected data available through state or
      national departments of labor and industry and/or occupational safety and health
      administrations. These data do not contain information on the severity or the
      sequelae of injuries. In addition, estimates of incidence may be biased due to
      inadequate data on the nature, amount, and seasonal variability of work done by
      adolescent workers. The present study is a cross-sectional survey of work and
      work injuries of 3,051 10th through 12th grade students from 39 high schools
      throughout Minnesota. Injury was defined as an event which caused any of the
      following: loss of consciousness, seeking medical care, and/or restricting normal
      activities for at least 1 day. The average hours of work per week during the
      summer and during the school year were 30 (95% Confidence Interval [CI] = 27, 33)
      and 16 (95% CI = 15, 17), respectively. There was no difference in hours worked
      between ethnic minorities and white students. The rate of reportable injuries was
      12 per 100,000 hr worked (95% CI = 7, 18) for rural and 13 per 100,000 hr worked
      (95% CI = 7, 28) for urban females, 16 (95% CI = 9, 22) per 100,000 hr for urban
      males, and 20 (95% CI = 12, 28) per 100,000 hr for rural males. Ongoing medical
      problems were reported by 26% of the injured workers. Previous estimates of work
      related injury to adolescents may have been low. More study is required to
      clearly define the incidence of injury and risk factors for these injuries.

PMID- 7810552
TI  - Mortality risk among elderly workers.
AB  - We analyzed population-based data for respondents aged 70 and older from the
      Longitudinal Study on Aging. We compared mortality risk among 358 baseline-year
      working with 4,373 nonworking respondents. Including other demographic and health
      status predictors in a multiple logistic regression model, employment remained a
      significant predictor of survival (mortality odds ratio (OR) = 0.4). Diabetes
      mellitus was the only factor that displayed a mortality risk that was
      significantly interactive with work (OR = 3.5). These data suggest that a healthy
      worker effect persists in older age groups, but that within the working stratum,
      patterns of risk may differ as compared to those among the nonworking.

PMID- 7810553
TI  - Lung cancer among steelworkers in Ontario.
AB  - A population-based case-control study was carried out to follow up observations
      of increased lung cancer risk in the steel pouring areas of two Ontario steel
      mills. Study subjects were all men, aged 45-75 years, who died of lung cancer in
      the cities of Hamilton or Sault Ste-Marie, Ontario from 1979-1988. Nine hundred
      sixty-seven lung cancer victims were matched with 2,827 control subjects who died
      of other causes. Work histories were provided by the employers of steelworkers.
      In comparison with other residents of their cities, the relative risk of death
      from lung cancer was 0.85 (95% confidence interval [CI]: 0.58-1.23) for
      steelworkers in Sault-Ste Marie and was 1.10 (95% CI: 0.89-1.37) for steelworkers
      in Hamilton. In internal comparisons within the steel companies, increased lung
      cancer risk was observed among foundry, coke oven, and pouring pit workers.
      Retrospective hygiene assessment suggested that the increased risk of lung cancer
      among steel pourers might be related to the use of tar-based mold coating agents
      or to exposure to mineral fibers.

PMID- 7810554
TI  - Fibrous glass and cancer.
AB  - Some argue that fibrous glass (glass wool) should not be considered as a likely
      human carcinogen and hence should not be listed in the Seventh Annual Report on
      Carcinogens (ARC) prepared by the National Toxicology Program (NTP) and mandated
      by the U.S. Congress. In examining this issue, data from both laboratory
      experiments (animal studies) and epidemiologic studies (human data) are reviewed
      with the results evaluated according to the criteria established by the
      International Agency for Research on Cancer (IARC) and adopted in slightly
      modified form by the NTP for classifying substances as human carcinogens or
      likely human carcinogens. From our comprehensive review of the available
      information, we conclude that fibrous glass materials are carcinogenic, and in
      view of the NTP and IARC definitions should be listed in the ARC. Our review then
      examines the carcinogenic potency of glass fibers to humans in comparison with
      asbestos fibers and concludes that on a fiber-per-fiber basis, glass fibers may
      be as potent or even more potent than asbestos. The implications of these
      findings are then presented for regulatory purposes in the occupational setting.

PMID- 7810555
TI  - Historical study: Cornelia C. de Lange (1871-1950)--a pioneer in clinical
      genetics.
AB  - The life and work in the field of clinical genetics of one of the most
      outstanding Dutch pediatricians of the first half of the twentieth century,
      Cornelia C. de Lange (1871-1950), is described against the background of the
      development of pediatrics, anthropogenetics, and clinical genetics in the
      Netherlands. Cornelia de Lange specialized in and worked on all aspects of the
      broad field of pediatrics. During her 50 years of practice she collected an
      immense series of observations on pediatric disorders. As theories on human
      genetics developed during the 1920s and 1930s, her interest in congential
      disorders and heredity increased as she saw the implications for the pediatric
      clinic. She benefitted from her vast experience and her knowledge of the national
      and international literature when she recognised and described new entities, one
      of which is named after her: the Brachmann-De Lange syndrome.

PMID- 7810556
TI  - Brachmann-de Lange syndrome "avant la lettre".

PMID- 7810557
TI  - DK-phocomelia syndrome in a child with a long follow-up.
AB  - We report on an 8-year-old boy with a pattern of multiple congenital anomalies
      that strongly suggest DK-phocomelia syndrome. Birth findings included bilateral
      upper limb amelia, occipital encephalocele, agenesis of the corpus callosum,
      right auricular tag, scoliosis, small penis, and cryptorchidism. Dental
      malocclusion was observed in the follow-up. This is the first case with on 8-year
      follow-up report of DK-phocomelia syndrome.

PMID- 7810558
TI  - von Voss-Cherstvoy syndrome: a variable perinatally lethal syndrome of multiple
      congenital anomalies.
AB  - We report 4 cases and review 7 from the literature with a pattern suggesting a
      variable early lethal multiple congenital anomaly syndrome. This was first
      reported by von Voss et al. [1979: "Klinische Genetik in der Padiatrie," pp 70
      74] and Cherstvoy et al. [1980: Lancet ii:485], and can affect upper limbs, face,
      brain, heart, lungs, urogenital and gastrointestinal systems, vertebrae and ribs,
      and can include thrombocytopenia. The initial cases had occipital encephaloceles
      and phocomelia, but milder cerebellar anomalies and radial ray defects may be
      seen instead. Both sexes are affected and parental age is not increased. This may
      be heterogeneous, but two consanguineous families, one with recurrences, suggest
      autosomal recessive inheritance in at least some instances, although the
      recurrences had milder brain findings than the other cases. The original
      designation of DK-phocomelia syndrome is inaccurate, since arm findings may be
      limited to radial anomalies; we suggest instead the von Voss-Cherstvoy syndrome.
      This may be heterogeneous, but at present, phenotypic overlap prevents
      differentiation of subgroups. The disorder appears to be part of a group of
      syndromes with radial and hematologic abnormalities.

PMID- 7810559
TI  - Comparative study of Fanconi anemia in children of different ethnic origin in
      South Africa.
AB  - A comparative study of clinical, hematologic, and cytogenetic findings was made
      in 40 black and 35 white children with Fanconi anemia. The black children were
      Bantu-speaking Negroid stock of diverse tribal origin. The white children were
      predominantly Afrikaans stock of Dutch/German/French Huguenot origin. All of the
      patients had IFAR scores of 2 to 4+ and over 80% in each group had increased
      spontaneous and/or mutagen-induced chromosomal breakage (CB-positive). There were
      no significant clinical differences between black and white patients or between
      CB-pos and CB-neg patients, with the exception of white children in whom
      significantly more CB-pos patients had thumb and radial anomalies than the CB-neg
      patients. The age-at-onset of hematologic manifestations was the same for all
      groups, but more black than white CB-pos patients were severely anemic at the
      time of diagnosis. Response to androgen and steroid therapy occurred in only 33%
      of black children compared with 86-90% of white children; 81% of black patients
      died during the 18 year study period compared with 30% of white children, but the
      age at death was similar. More sophisticated studies are required to determine
      whether these differences are genetically determined or related to cultural,
      educational, and socio-economic differences between the two ethnic groups.

PMID- 7810560
TI  - Three decades of follow-up of aortic and pulmonary vascular lesions in the
      Williams-Beuren syndrome.
AB  - The diagnostic criteria of the Williams-Beuren syndrome (WBS) were established
      almost 3 decades ago. Until now there has been little knowledge about the natural
      and post-surgical history of vascular lesions in this syndrome. In order to
      evaluate the long term follow-up of aortic and pulmonary vascular lesions, we
      have analysed the catheterization data, angiocardiograms, and Doppler-echo
      measurements in 59 patients who were seen at least twice in our institution
      between 1961 and 1993. Their follow-up periods ranged from 2.1 to 28.2 years. Of
      45 patients with supravalvular aortic stenosis (SVAS) with a mean follow-up
      period of 12.9 years, it became evident that pressure gradients of less than 20
      mm Hg in infancy generally remained unchanged during the first two decades of
      life. Pressure gradients exceeding 20 mm Hg increased from an average of 35.5 mm
      Hg to 52.7 mm Hg in 13 patients. Of these, 8 required surgical relief of the
      narrowing. In 7 patients aortic hypoplasia was documented. In 5 of them the
      caliber of the aorta showed a tendency towards normalisation within a period of
      11.9 to 23.9 years. Of 6 individuals with aortic hypoplasia and surgical relief
      of SVAS, 4 patients developed restenosis at the distal end of the aortoplasty
      patch. In contrast, 9 patients with operated SVAS-but without aortic hypoplasia
      remained free of restenosis over a period of 11 years (mean). Coarctation
      occurred in 4/59 patients; restenosis was seen in 2 after 5 and 16 years.
      Peripheral pulmonary stenosis was followed in 23 patients over 14.4 years
      (mean).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7810561
TI  - Six additional cases of the KBG syndrome: clinical reports and outline of the
      diagnostic criteria.
AB  - A diagnosis of KBG syndrome was made in six unrelated patients. They presented
      with slight mental retardation, macrodontia, and skeletal abnormalities.
      Microcephaly, short stature, facial anomalies, and syndactylies were also noted.
      The diagnostic criteria of the KBG syndrome are discussed.

PMID- 7810562
TI  - Segregation analysis of smoking-associated malignancies: evidence for Mendelian
      inheritance.
AB  - Tobacco consumption is an established risk factor for cancer at a number of
      sites: oral cavity, esophagus, nasopharynx, lung, larynx, pancreas, bladder,
      kidney, and uterine cervix. These sites also demonstrate familial aggregation. To
      determine if evidence exists for a major gene controlling susceptibility to
      smoking-associated cancers, maximum likelihood segregation analyses were
      performed on 337 families (3,276 individuals) ascertained through a deceased lung
      cancer proband. Models were fitted that allowed for personal tobacco use and
      variable age of onset. The hypotheses of environmental transmission and no major
      gene were rejected (P < 0.005), but none of the Mendelian models could be
      distinguished. According to Akaike's Information Criterion, Mendelian dominant
      inheritance of an allele that produces cancer at an earlier age of onset provided
      the best fit to the data. The model suggests that 62% of the population are
      susceptible, and that the mean age-of-onset differs for men and women: at the
      mean level of tobacco exposure, female gene carriers are affected, on average, 24
      years earlier than non-carriers (77 vs. 101), while in males the difference was
      20 years (71 vs. 91). These findings extend our earlier observations on the
      genetic epidemiology of lung cancer and suggest that Mendelian factors may
      influence the risk of cancers that are known to be smoking associated.

PMID- 7810563
TI  - Apparently normal frequency of congenital anomalies in the highly polluted town
      of Cubatao, Brazil.
AB  - Anencephaly is Suspected to cluster in the municipality of Cubatao (Brazil), and
      is attributed to industrial pollution. We surveyed malformations prospectively in
      10,000 births, in 3 consecutive series, corresponding to 3 maternity hospital in
      Cubatao, under working definitions and norms taken from the ECLAMC (Latin
      American Collaborative Study of Congenital Malformations). The sample from
      Cubatao had a higher proportion of black racial ancestry, and lower frequencies
      for stillbirths and for immediate neonatal death, than in the rest of South
      America. The birth prevalence of malformations varied between the 3 hospitals in
      Cubatao, due to differences in ascertainment of minor defects. A higher-than
      expected prevalence rate in Cubatao was observed only for postaxial polydactyly,
      probably due to a higher proportion of black racial ancestry, while lower-than
      expected rates were obtained for congenital dislocation of the hip, and for
      babies with multiple congenital anomalies patterns, both of them attributed to
      underascertainment of minor defects. These observations do not support the
      suspicion of an elevated birth prevalence rate for anencephaly, neural tube
      defects, or any other major congenital malformation in Cubatao.

PMID- 7810564
TI  - Mixoploidy in humans: two surviving cases of diploid-tetraploid mixoploidy and
      comparison with diploid-triploid mixoploidy.
AB  - We report on 2 cases of diploid/tetraploid (2n/4n) mixoploidy in surviving
      females, 11 and 21 years old. Both individuals manifested severe mental
      retardation, reduced peripheral limb muscle bulk, asymmetric growth deficiency,
      seizure disorder, and skin pigmentary dysplasia. Previous lymphocyte karyotypes
      had been normal on 2 occasions, but when skin fibroblast karyotypes were done,
      33% of the cells were tetraploid on the younger woman, and over 60% were
      tetraploid in the older woman (on 2 separate occasions). In both individuals, the
      distal limbs and digits were long and thin, with reduced small muscle bulk. The
      similarity in distal limb findings prompted reexamination of the younger woman's
      chromosomal constitution in skin fibroblasts. We concluded that the clinical
      findings in these cases are unique and similar, and we caution clinicians about
      uniformly dismissing tetraploidy as artifactual in amniocytes from normal
      patients, especially since this phenotype would be very difficult to detect, even
      with directed prenatal ultrasonography. We compare the 2n/4n phenotype with that
      in diploid/triploid (2n/3n) mixoploidy and note subtle differences which might be
      detected postnatally. These findings should be useful in guiding clinicians on
      when to request skin fibroblast karyotypes in mentally-deficient individuals with
      asymmetric growth deficiency and pigmentary skin variation.

PMID- 7810565
TI  - Syndrome of hypoparathyroidism, growth hormone deficiency, and multiple minor
      anomalies.
AB  - A 5 1/2-year-old Saudi Arabian girl presented with a syndrome of intrauterine
      growth retardation, minor anomalies, hypoparathyroidism, and growth hormone
      deficiency. She was the product of a consanguineous mating. Her minor anomalies
      and delayed development were similar to findings in a previously reported Saudi
      Arabian patients with hypoparathyroidism and growth deficiency. There were
      substantial differences in findings from a series of Kuwaiti children.
      Parathyroid hormone was undetectable, but the renal response to infused
      parathyroid hormone was normal, indicating primary hypoparathyroidism. In
      response to arginine stimulation, her GH rose to 5.8 ng/ml (5.8 micrograms/L) (nl
      > 10), and to 2.3 ng/ml (2.3 micrograms/L) after L-dopa. Following clonidine it
      rose to 15 ng/ml (15 micrograms/L) at 120 minutes. She responded normally to
      infusions of GHRH (GH rose to 22 ng/ml (22 micrograms/L) at 75 minutes) and TRH
      (TSH rose to 37 mu u/ml, 37 mIU/L). On treatment with recombinant human growth
      hormone, she showed an increase in height and weight. Hypocalcemia was well
      controlled with supplemental 1-alpha-cholecalciferol.

PMID- 7810566
TI  - Aarskog-Scott syndrome: confirmation of linkage to the pericentromeric region of
      the X chromosome.
AB  - Aarskog-Scott syndrome was tentatively mapped to Xq13 on the basis of an X:8
      translocation by Bawle et al. [Am J Med Genet 17:595-602, 1984]. A review of the
      cytogenetics and the use of molecular markers in that family have resulted in
      revision of the breakpoints of the translocation to Xp 11.2 and 8q11.21 [Glover
      et al., Hum Mol Genet 2:1717-1718, 1993]. Two families, including one of the two
      initial families with Aarskog-Scott syndrome [Scott, BD:OAS VII (6): 240-246,
      1971], have participated in our study to evaluate the localization of the gene
      for Aarskog-Scott syndrome to the pericentromeric region of the X chromosome.
      Using a series of DNA probes, we have been able to confirm linkage to the X
      chromosome, with multipoint analysis indicating the most likely localization of
      the gene to be on the proximal short arm.

PMID- 7810567
TI  - FISH mapping of a human chromosome 16 constitutional pericentric inversion
      inv(16)(p13q22) found in a large kindred.
AB  - Fluorescence in situ hybridization analysis (FISH) was used to map the
      constitutional chromosome 16 pericentric inversion breakpoints inv(16)(p13q22)
      detected in one individual (II-2) from a large kindred [Bianchi et al., 1992: Am
      J Med Genet 43:791-795]. The breakpoints found in individual II-2 mapped to
      distinctly different locations than the chromosome 16 pericentric inversion
      breakpoints commonly acquired in acute nonlymphocytic leukemia. The
      constitutional pericentric inversion breakpoints also do not map to regions where
      low abundance repetitive DNA sequences found in bands 16p13 and q22 are located.
      The results indicate that low abundance, chromosome 16-specific repetitive DNA
      sequences in bands p13 and q22 are probably not causally related to the inversion
      that is found in many members of a large kindred [Bianchi et al., 1992].

PMID- 7810568
TI  - Direct and inverted reciprocal chromosome insertions between chromosomes 7 and 14
      in a woman with recurrent miscarriages.
AB  - We present the first case of direct and inverted reciprocal chromosome insertions
      between human chromosomes 7 and 14, ascertained because of repeated spontaneous
      abortions. Prometaphase GTG banding analysis showed the karyotype to be 46, XX,
      inv ins (7;14)(7pter-->7q11.23::14q32.2-->14q 22::7q21.2-->7qter), dir
      ins(14;7)(14pter-->14q 22::7q11.23-->7q21.2::14q32.2-->14qter). Origins of the
      insertion have been confirmed by chromosome painting with libraries specific for
      chromosomes 7 and 14 using fluorescence in situ hybridization.

PMID- 7810569
TI  - Familial Angelman syndrome with a crossover in the critical deletion region.
AB  - More than two thirds of the patients with Angelman syndrome (AS) carry a deletion
      or other chromosomal abnormality in the 15q11-13 region. A much less frequent
      cause (4%) is paternal uniparental disomy of the entire chromosome. In general no
      abnormalities are detectable in familial cases and an inherited submicroscopic
      deletion was described only once. Here a familial case of 2 sibs with AS is
      reported. No major cytogenetic or molecular abnormality was identified, but a
      recombination event had occurred in the AS critical region. The AS locus,
      D15S113, D15S10, D15S11, and D15S18 mapped proximal and the GABRB3 gene, D15S97,
      the GABRA5 gene, and D15S12 distal to the crossover site. This recombination
      within the AS critical region confirmed the exclusion of GABRB3 as a candidate
      gene for AS. Other markers and candidate genes can be tested genetically as well
      for a possible role in AS.

PMID- 7810570
TI  - Balanced complex chromosome rearrangement ascertained through prenatal diagnosis.

PMID- 7810571
TI  - Inbreeding among medical geneticists. II.

PMID- 7810572
TI  - Exclusively maternal transmission of autosomal dominant Brachmann-de Lange
      syndrome.

PMID- 7810573
TI  - Predictive testing for Huntington disease: a psychologist's view.

PMID- 7810574
TI  - Self-selection in predictive testing for Huntington's disease.
AB  - Several studies have reported favorable psychological reactions to predictive
      testing for Huntington's disease (HD). However, few at-risk persons have been
      tested, and there is evidence that some at-risk people avoid testing because they
      fear being unable to cope with the information. Favorable psychological reactions
      may result from self-selection of persons who believe they are better-equipped to
      handle "bad news." We surveyed 32 at-risk persons who had considered, but not
      chosen, testing and 66 persons who had been previously tested. Twelve persons
      decided not to be tested (No group); 20 persons postponed testing until some
      later date (Maybe group). Of the two untested groups, a significantly greater
      number of the No group had not been tested because they anticipated problems
      associated with their emotional reactions. The persons in the Tested group had
      less often anticipated problems with their emotional reactions; and among the
      minority who had anticipated some problems, most did not question their ability
      to cope. We conclude that the Tested persons are psychologically selected for
      favorable responses to genetic testing. Surveys of health professionals suggest
      that a sizable minority would disclose genetic disease risk whether or not people
      want it. Thus, people who would not choose to be tested might be persuaded to do
      so, or have results thrust upon them. We should be wary about assuming that the
      generally favorable reactions to HD testing will continue when testing becomes
      more widespread, as is likely to happen with simplification of the technology and
      acceptance of these tests by the medical community.

PMID- 7810575
TI  - Psychological costs and benefits of predictive testing for Huntington's disease.
AB  - The impact of predictive genetic testing for Huntington's disease (HD) was
      assessed in 68 persons at high (n = 17) or low risk (n = 51) for the disease at
      one to six years following disclosure of test results. There was consensus in
      both groups that knowledge of HD genetic status was beneficial. A majority of
      persons felt relief from wondering and uncertainty. High-risk persons identified
      greater family closeness and financial security. For low-risk persons, the
      knowledge that their children were spared offered great consolation. Negative
      effects in high-risk persons were psychological burden (worry, guilt). Even for
      low-risk subjects, there was a period of adjustment and, in some, disappointment
      that low risk had not alleviated problems unrelated to HD. Although the majority
      of marriages were unaffected by testing, some persons in both groups reported
      that their marriages sustained positive or negative impact. Despite mixed
      consequences, most did not regret being tested. The benefits of testing appear to
      outweigh its drawbacks, at least among this self-selected group of research
      participants. We also must conclude, however, that predictive genetic testing
      will result in negative as well as positive consequences, regardless of test
      outcome.

PMID- 7810576
TI  - Psychiatric genetics: research challenges and pathways forward.
AB  - Lessons from past psychiatric genetic research, together with key issues in
      psychiatry requiring genetic investigation, are reviewed in order to consider the
      implications for the ways forward. It is argued that traditional quantitative
      genetics needs to use a combination of twin, adoptee, and family strategies, to
      examine continuities and discontinuities in psychopathology between childhood and
      adult life, to compare dimensions and categories, to employ adequate
      conceptualization and measurement of disorders, to use statistical techniques
      based on latent constructs, to use biological trait indicators where possible, to
      examine risk factors as well as diseases, to include good measures of postulated
      environmental risk variables, to study the interplay between genes and
      environment, and to study the key assumptions underlying genetic strategies.
      Molecular cytogenetics needs to consider both the general and specific
      psychopathological risks associated with chromosome abnormalities and to examine
      the mechanism involved, to examine the role of submicroscopic chromosomal
      deletions and of mitochondrial disorders, and to investigate the mechanisms
      involved in trinucleotide repeat amplifications that take place during
      intergenerational transmission. Molecular genetics needs to make greater use of
      smaller pedigrees in view of the concerns over phenotypic definition and genetic
      heterogeneity in very large extended dense pedigrees, to use sib-pair designs in
      view of the likelihood that most psychiatric disorder will prove to be
      multifactorial, to combine association strategies with linkage analyses, to pay
      careful attention to the definition of phenotypes in probands, to remain in close
      touch with other branches of biological psychiatry, and to make effective use of
      collaboration between centers. To date, transgenic models have had a rather
      limited application in psychiatry but, despite their difficulties, they are
      likely to provide an underpinning for gene therapy in disorders where that seems
      feasible.

PMID- 7810577
TI  - Association of the apolipoprotein E epsilon 4 allele with clinical subtypes of
      autopsy-confirmed Alzheimer's disease.
AB  - Consistent with previous reports, we observed a significant association of the
      APOE epsilon 4 allele with Alzheimer's Disease (AD) in a series of 91 autopsy
      confirmed cases. The epsilon 4 allele frequency was higher in cases with a family
      history of AD-like dementia (0.54 +/- 0.07), although the epsilon 4 allele
      frequency in the AD cases with a negative family history (0.38 +/- 0.05) remained
      significantly greater than that for the non-AD control group (0.13 +/- 0.03). A
      similar increase in epsilon 4 allele frequency (0.54 +/- 0.07) was observed in
      the AD cases with amyloid angiopathy, compared to those who did not have amyloid
      angiopathy (0.36 +/- 0.04). Contrary to previous reports, no effect of the dosage
      of the epsilon 4 allele was found on the age of onset of dementia among the AD
      cases and, contrary to reports suggesting an association of epsilon 4 and
      atherosclerosis, the epsilon 4 allele frequency was similar in cases with or
      without concurrent brain infarcts. Modest but consistent correlations were
      observed between the dosage of epsilon 4 alleles and the cortical density of
      senile plaques, but not neurofibrillary tangles. The last finding suggests that
      the pathogenic events mediated by the epsilon 4 allele may be more directly
      involved in the formation of senile plaques, the identifying lesions in AD, than
      neurofibrillary tangles. A robust association of both the presence of an epsilon
      4 allele and a family history of AD-like dementia with concurrent amyloid
      angiopathy occurred within our sample of AD cases. This association arose from an
      interaction of the epsilon 4 allele with a separate familial factor for which a
      family history of dementia served as a surrogate. These results suggest that
      amyloid angiopathy may be a common or central feature of a form of familial AD
      that is associated with the transmission of the APOE epsilon 4 allele.

PMID- 7810578
TI  - Genetic linkage mapping for a susceptibility locus to bipolar illness:
      chromosomes 2, 3, 4, 7, 9, 10p, 11p, 22, and Xpter.
AB  - We are conducting a genome search for a predisposing locus to bipolar (manic
      depressive) illness by genotyping 21 moderate-sized pedigrees. We report linkage
      data derived from screening marker loci on chromosomes 2, 3, 4, 7, 9, 10p, 11p,
      22, and the pseudoautosomal region at Xpter. To analyze for linkage, two-point
      marker to illness lod scores were calculated under a dominant model with either
      85% or 50% maximum penetrance and a recessive model with 85% maximum penetrance,
      and two affection status models. Under the dominant high penetrance model the
      cumulative lod scores in the pedigree series were less than -2 at theta = 0.01 in
      134 of 142 loci examined, indicating that if the disease is genetically
      homogeneous linkage could be excluded in these marker regions. Similar results
      were obtained using the other genetic models. Heterogeneity analysis was
      conducted when indicated, but no evidence for linkage was found. In the course of
      mapping we found a positive total lod score greater than +3 at the D7S78 locus at
      theta = 0.01 under a dominant, 50% penetrance model. The lod scores for
      additional markers within the D7S78 region failed to support the initial finding,
      implying that this was a spurious positive. Analysis with affected pedigree
      member method for COL1A2 and D7S78 showed no significance for linkage but for
      PLANH1, at the weighting functions f(p) = 1 and f(p) = 1/sqrt(p) borderline P
      values of 0.036 and 0.047 were obtained. We also detected new polymorphisms at
      the mineralocorticoid receptor (MLR) and calmodulin II (CALMII) genes. These
      genes were genetically mapped and under affection status model 2 and a dominant,
      high penetrance mode of transmission the lod scores of < -2 at theta = 0.01 were
      found.

PMID- 7810579
TI  - A variety of genetic mechanisms are associated with the Prader-Willi syndrome.
AB  - An extensive set of chromosome 15 DNA polymorphisms and densitometric analysis
      with four markers mapping to the Prader-Willi chromosome region (PWCR) of
      chromosome 15 have been used to characterize a cohort of 30 subjects with
      classical Prader-Willi syndrome (PWS). Molecular analysis enabled the
      classification of the PWS subjects into four groups: (A) 18 subjects (60%) had
      deletions of paternal 15q11-13 involving a common set of DNA markers. Two
      subjects had differently sized deletions, one larger and one smaller than the
      other cases. (B) Eight (27%) had maternal uniparental disomy for chromosome 15.
      (C) One (3%) had a marker chromosome carrying an extra copy of the PWCR. The
      marker chromosome was demonstrated to be of paternal origin and the two intact
      chromosomes were maternally derived. This case represents an apparent exception
      to the generally held view that PWS is associated with an absence of paternally
      inherited gene(s) located in the PWCR. (D) The remaining three cases (10%) had
      none of the above abnormalities. This last subgroup of patients has not
      previously been well characterized but could represent limited deletions not
      detectable with the markers used or abnormalities in the imprinting process.
      These cases represent potentially valuable resources to elucidate more precisely
      the fundamental disorders responsible for PWS.

PMID- 7810580
TI  - Role of genetic factors in human sexual behavior based on studies of Tourette
      syndrome and ADHD probands and their relatives.
AB  - Most significant variations in the expression of human sexuality are considered
      to be the result of learned behavior or psychological problems. Tourette syndrome
      (TS) is a common, hereditary tic and disinhibition disorder sometimes associated
      with compulsive use of obscene words (coprolalia) and previously reported to be
      occasionally associated with exhibitionism. To further explore the relationship
      between the Gts genes and sexual behavior, questions concerning a wide range of
      such behaviors were administered to 1,040 subjects, 14 years of age or older,
      consisting of 358 TS probands, 101 non-proband relatives with TS, 359 non-TS
      first degree relatives, 79 attention deficit hyperactivity disorder (ADHD)
      probands, 70 unaffected relatives of the ADHD probands, and 73 controls. The
      behaviors included magnitude of sex drive, sex orientation, exhibitionism,
      transvestitism, transsexualism, sadism, masochism, pedophilia, fetishism,
      aversion to being touched, and aversion to sex. While most of these behaviors
      occurred in a distinct minority of TS subjects, there was a significant positive
      correlation between each behavior examined and the degree of genetic loading for
      the Gts gene(s). The nature of these behaviors and their association with TS
      suggests many are variants of obsessive-compulsive disorder. Studies in animals
      indicate that changes in serotonin and dopamine play a significant role in the
      sexual behavior and many lines of evidence are consistent with the hypothesis
      that TS is due to genetic changes in serotonin and dopamine metabolism. These
      studies suggest that genetic factors play a much greater role in a wide range of
      forms of sexual expression than previously thought.

PMID- 7810581
TI  - Knowledge of genetics and attitudes toward genetic testing in two hereditary
      ataxia (SCA 1) kindreds.
AB  - Molecular genetic predictive or prenatal genetic testing is now possible in
      families with one form of adult-onset, autosomal dominant ataxia (SCA 1). Before
      the SCA 1 gene was isolated, we began a study of the knowledge of genetics, the
      perception of the disease, and the intended use of genetic testing among members
      of two large SCA 1 kindreds. Questionnaires were sent to 210 consenting affected,
      at-risk, and spouse members of two SCA 1 kindreds; data from the 117 respondents
      were analyzed on a personal computer. Sixty-nine percent of respondents thought
      predictive testing (by genetic linkage) should be made available immediately, and
      42% thought prenatal testing should be made available. The kindreds differed in
      several important aspects: knowledge of genetic concepts, family size, and
      anticipated emotional responses to genetic testing. No respondent had obtained
      individualized genetic counseling. There is moderate interest in genetic testing
      for this fatal neurodegenerative disease of adulthood. Members of our kindreds
      have not received genetic counseling outside of the research setting. Finally,
      factors specific to a particular kindred may influence or predict individual
      responses to genetic testing.

PMID- 7810582
TI  - Association analysis of the dopamine D2 receptor gene in Tourette's syndrome
      using the haplotype relative risk method.
AB  - Comings et al. [1991: JAMA 266: 1793-1800] have recently reported a highly
      significant association between Tourette's syndrome (TS) and a restriction
      fragment length polymorphism (RFLP) of the dopamine D2 receptor gene (DRD2)
      locus. The A1 allele of the DRD2 Taq I RFLP was present in 45% of the Tourette
      patients compared with 25% of controls. We tried to replicate this finding by
      using the haplotype relative risk (HRR) method for association analysis. This
      method overcomes a major problem of conventional case-control studies, where
      undetected ethnic differences between patients and controls may result in a false
      positive finding, by using parental alleles not inherited to the proband as
      control alleles. Sixty-one nuclear families encompassing an affected child and
      parents were typed for the DRD2 Taq I polymorphism. No significant differences in
      DRD2 A1 allele frequency were observed between TS probands, subpopulations of
      probands classified according to tic severity, or parental control alleles. Our
      data do not support the hypothesis that the DRD2 locus may act as a modifying
      gene in the expression of the disorder in TS probands.

PMID- 7810583
TI  - Lack of association between obsessive-compulsive disorder and the dopamine D3
      receptor gene: some preliminary considerations.
AB  - Controversial results possibly suggesting an association between Tourette's
      Syndrome (TS) and excess of homozygosity at a Msc I polymorphism in the Dopamine
      D3 receptor (DRD3) gene have recently been reported. Since a relationship between
      Obsessive-Compulsive Disorder (OCD) and Tourette's Syndrome (TS) has been
      suggested, in this study we assessed the frequency of this 2-allele polymorphism
      in a sample of 97 OCD patients and in 97 control subjects. No statistically
      significant differences in allele or genotype frequencies were found. Thus this
      mutation in the coding sequence of the DRD3 gene is unlikely to confer
      susceptibility to OCD.

PMID- 7810584
TI  - Repeat length variation in the dopamine D4 receptor gene shows no evidence of
      association with schizophrenia.
AB  - The D4 receptor has been shown to exist in several allelic forms (Van Tol et al.,
      Nature 358:149-152, 1992) reflecting variation in the number of 48 base-pair
      sequence repeats in the putative cytoplasmic loop. We report a comparison of
      repeat length variation between schizophrenic patients and controls. Our sample
      of 106 unrelated schizophrenic cases and 119 controls showed no significant
      differences in allele or genotype distribution between patients and controls. In
      particular, we were unable to support the previous observation of an excess of 4
      repeat homozygotes in patients.

PMID- 7810585
TI  - No evidence of association between dopamine D4 receptor variants and bipolar
      affective disorder.
AB  - Disturbance in the dopamine neurotransmitter system has been implicated in the
      pathogenesis of affective disorder. In this study, we examine the possibility
      that functional variants of the recently cloned dopamine D4 receptor gene
      contribute to the genetic component of manic depression. The polymorphism, a 48
      bp tandem repeat coding for part of the third cytoplasmic loop, was detected
      using a PCR based method. In a first sample of 57 patients and 59 controls, we
      found allele 7 to be in excess in the patients. In contrast, allele 3 was less
      frequent in patients. A second, larger sample of 90 patients and 91 controls was
      utilized to test these hypotheses. Data from the two samples were then pooled
      together for further analyses. We calculated the power of our samples, and if the
      frequency of 7 repeat allele obtained from sample 1 is true, i.e., 25% (28/114)
      for patients and 14% (16/118) for controls, then the power of the combined sample
      is 62% at 5% (two-tailed) significance level. However, both observations were not
      replicated; we therefore conclude that variations in this repeat at the DRD4 gene
      do not contribute to the genetic component of manic depression.

PMID- 7810586
TI  - Further evidence of no linkage between schizophrenia and the dopamine D3 receptor
      gene locus.
AB  - The dopamine hypothesis of schizophrenia proposed that dopaminergic pathways are
      involved in the etiology of the disease. In particular, interest among
      psychiatrists has focused on the D2 receptor because of its affinity to
      antipsychotic drugs. Recently a new dopamine receptor gene has been cloned, and
      named the dopamine D3 receptor. The D3 receptor is a potential site for
      antipsychotic drug action and may be involved in the pathophysiology of
      schizophrenia. We have carried out a linkage study between the susceptibility
      gene for schizophrenia and polymorphism of the dopamine D3 receptor gene in two
      Japanese pedigrees. The LOD scores were negative for all genetic models and for
      all affective status at a recombination fraction theta = 0. Linkage of DRD3 has
      been excluded for the model 1 (dominant model) and the model 3 (recessive model).
      The LOD score was -3.43 at theta = 0 for model 1 (dominant model) and broad
      definition of affected status. These results were consistent with previous
      studies.

PMID- 7810587
TI  - Partial trisomy 16p in an adolescent with autistic disorder and Tourette's
      syndrome.
AB  - A partial trisomy 16p was identified in a 14-year-old male adolescent with
      autistic disorder. He additionally showed complex motor and vocal phenomena,
      including some simple tics which had first appeared in childhood. Whereas these
      simple tics were of subclinical significance, an additional diagnosis of
      Tourette's syndrome (TS) appears justified. The case report illustrates the
      diagnostic difficulties in assessing psychiatric symptomatology associated with
      both disorders, especially complex motor and vocal phenomena. The cytogenetic
      finding is discussed critically in the light of other chromosome abnormalities
      reported in both TS and autistic disorder. Chromosome 16p should be considered as
      a candidate region especially for autistic disorder.

PMID- 7810588
TI  - Elevated risks for amyotrophic lateral sclerosis and blood disorders in Ashkenazi
      schizophrenic pedigrees suggest new candidate genes in schizophrenia.
AB  - Among relatives of Ashkenazi schizophrenic probands the rate of amyotrophic
      lateral sclerosis was 3/1,000, compared to expected population rates of
      approximately 2/100,000. Relative risk of bleeding disorders, including
      hematologic cancers, was increased more than three-fold compared to controls. Co
      occurrence of motor neuron disease and blood dyscrasias, accompanied by
      psychosis, has long been recognized. A virally mediated autoimmune pathogenesis
      has been proposed. However, the familial co-occurrence of these three disease
      entities raises the possibility that the disease constellation be considered as a
      manifestation of a common underlying genetic defect. Such expansion of the
      spectrum of affectation might enhance the power of both candidate gene and
      linkage studies. Based on these findings the loci suggested as candidate regions
      in schizophrenia include a potential hot spot on chromosome 21q21-q22, involving
      the superoxide dismutase and amyloid precursor protein genes. Alternatively,
      genes on other chromosomes involved in the expression, transcription, or
      regulation of these genes, or associated with the illnesses of high frequency in
      these pedigrees are suggested. Candidates include the choroid plexus transport
      protein, transthyretin at 18q11.2-q12.1; the t(14;18)(q22;21) characterizing B
      cell lymphoma-2, the most common form of hematologic cancer; and the 14q24 locus
      of early onset Alzheimer's disease, c-Fos, transforming growth factor beta 3, and
      heat shock protein A2. Expression of hematologic cancers and the suggested
      candidate genes are known to involve retinoid pathways, and retinoid
      disregulation has been proposed as a cause of schizophrenia.

PMID- 7810589
TI  - Comparison of schizotypal relatives of schizophrenic versus affective probands.
AB  - In order to investigate possible heterogeneity in schizotypal personality
      disorder (SPD), two groups of schizotypals, one related to schizophrenic probands
      (FSPD) (n = 34) and one related to affective disorder probands (NFSPD) (n = 14),
      ascertained in the same family study, were compared. The FSPD group had more
      inadequate rapport; the groups did not differ in the frequency of any other
      symptoms of SPD. NFSPDs had higher rates of comorbid histrionic PD and a trend
      for higher rates of impulsive/dramatic cluster PDs. FSPDs had a trend for higher
      rates of anxiety disorders. There was a higher risk of bipolar disorder in the
      relatives of NFSPDs and higher risk for anxiety disorders in the relatives of
      FSPDs. The relatives of NFSPDs had higher rates for histrionic, narcissistic, and
      atypical PDs and for having at least one PD.

PMID- 7810591
TI  - 15th Annual meeting of the Society of Perinatal Obstetricians. Atlanta, Georgia,
      January 23-28, 1995. Abstracts.

PMID- 7810590
TI  - Association of apolipoprotein E allele epsilon 4 with late-onset sporadic
      Alzheimer's disease.
AB  - Apolipoprotein E, type epsilon 4 allele (ApoE epsilon 4), is associated with late
      onset sporadic Alzheimer's disease (AD) in French patients. The association is
      highly significant (0.45 AD versus 0.12 controls for epsilon 4 allele
      frequencies). These data support the involvement of ApoE epsilon 4 allele as a
      very important risk factor for the clinical expression of AD.

PMID- 7810592
TI  - Antidiuretic hormone and exocytosis: lessons from neurosecretion.
AB  - Many cells, both single and epithelial, are programmed for exocytosis. In most
      cases, the contents of cytoplasmic vesicles are delivered rapidly and directly to
      the extracellular fluid. The process has been intensively studied in the
      chromaffin cell and the nerve terminal, where, as in other cells, exocytosis is
      under a complex type of cytoskeletal control. An array of vesicle-associated
      proteins mediates attachment of the vesicles to the cytoskeleton, their release,
      and their fusion with the plasma membrane. Two functional pools of vesicles, the
      releasable and reserve pool, carry out immediate and long-term secretory
      activity. Some of the mediators of neurotransmitter vesicle fusion, originally
      thought to be restricted to neurosecretory cells, have now been found in
      nonneuronal cells. The mammalian collecting duct and the amphibian bladder are
      also engaged in exocytosis. In both epithelia, antidiuretic hormone (ADH) induces
      the transfer of water channels from cytoplasmic vesicles to the apical cell
      membrane. The process is slower than in the nerve terminal and ends with channel
      placement rather than the extrusion of vesicular contents. Nevertheless, there
      are several respects in which cytoskeletal control, vesicle positioning in the
      cell, docking, and fusion may prove to resemble the events in neurosecretion.
      This review begins with a survey of cytoskeletal structure and function in the
      erythrocyte, the chromaffin cell, and the nerve terminal and then presents
      current studies of ADH-induced exocytosis, emphasizing common themes in
      cytoskeletal control.

PMID- 7810593
TI  - Carrier-mediated transport of lipoxin A4 in human neutrophils.
AB  - Lipoxins and other eicosanoids display potent and selective biological effects on
      leukocytes. In this study, we utilized radiolabeled lipoxin A4 ([3H]LXA4) to
      investigate whether carrier-mediated transport of LXA4 might occur in human
      neutrophils. At a concentration of 5 nM, uptake of [3H]LXA4, above that due to
      specific binding to receptors, amounted to approximately 0.6 fmol.10(6) cells
      1.min-1. This influx was sensitive to a number of anionic inhibitors, including
      3,5-diiodosalicylic acid (K0.5 12 microM), pentachlorophenol (K0.5 25 microM),
      alpha-cyano-beta-(1-phenylindol-3-yl) acrylic acid, and the organomercurial
      agents mersalyl (K0.5 110 microM) and p-hydroxy-mercuribenzoate. Influx, which
      was Na+ and membrane voltage independent, exhibited a striking dependence on pH
      (negative log of dissociation 5.9), results compatible with an H+ + LXA4 anion
      cotransport system. The LXA4 carrier did not appear to interact with arachidonic
      acid, prostaglandin E2, 15(S)-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoic acid, or
      the leukotrienes B4, C4, and D4. Moreover, transport activity was not observed in
      human erythrocytes, lymphocytes, or platelets, but it was inducible in HL-60
      cells on differentiation by exposure to retinoic acid. These findings represent
      the identification and initial characterization of a novel carrier-mediated
      pathway in human neutrophils that facilitates transport of LXA4 into cells.

PMID- 7810594
TI  - Swelling-activated K+ fluxes in vascular endothelial cells: role of intracellular
      Ca2+.
AB  - Swelling of bovine aortic endothelial cells activates Ca(2+)-dependent K+
      channels. To determine the role of Ca2+ in this response, we examined the effect
      of cell swelling on intracellular Ca2+ concentration ([Ca2+]i), and the role of
      [Ca2+]i in swelling-activated K+ efflux. Basal [Ca2+]i, measured by fura 2
      fluorescence, was 62 nM and increased by 36 nM in hypotonic medium (220 mosmol/l)
      compared with a 277 nM increase in response to extracellular ATP. In cells loaded
      with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid (BAPTA), the
      increases induced by swelling and by ATP were reduced to 13 and 20 nM,
      respectively. Exposure to hypotonic medium (220 mosmol/kg) or to the Ca2+
      ionophore A-23187 stimulated a furosemide-insensitive 86Rb efflux consistent with
      activation of K+ channels. The swelling-activated efflux was inhibited 16% by 5
      mM tetraethylammonium and 24% by 23 mM tetrabutylammonium, but not by 100 microM
      quinidine, a pattern similar to that previously observed for swelling-activated
      K+ channels in cell-attached patches. The effects of A-23187 and hypotonic
      swelling on 86Rb efflux were completely additive, suggesting Ca(2+)-independent
      activation by cell swelling. Removal of Ca2+ from the external medium or loading
      of cells with BAPTA to buffer intracellular Ca2+ blocked the activation of 86Rb
      efflux by A-23187, but not by hypotonic swelling. Hypertonic medium (440
      mosmol/kg by the addition of sucrose) attenuated the increased 86Rb efflux in
      response to A-23187. We conclude that the activation of K+ efflux in swollen
      endothelial cells occurs independently of changes in [Ca2+]i.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7810595
TI  - Role of external Na+ and cytosolic pH in agonist-evoked cytosolic Ca2+ response
      in human platelets.
AB  - The role of external Na+ in agonist-evoked platelet Ca2+ response is poorly
      understood. This was explored in this study. Removal of external Na+ decreased
      both cytosolic Ca2+ mobilization and external Ca2+ entry, induced by thrombin but
      not by ADP or vasopressin. That external Na+ regulates thrombin activities was
      demonstrated by 1) Na+ dependency of the amidolytic activity of thrombin, 2)
      inhibition of thrombin binding to the high-affinity binding sites in Na(+)-free
      medium, and 3) attenuation of thrombin-induced inositol 1,4,5-trisphosphate
      production in Na(+)-free medium. Moreover, Ca2+ response to the thrombin receptor
      6-amino acid peptide was independent of external Na+. The role of external Na+ in
      modifying agonist-evoked Ca2+ response through activation of Na+/H+ antiport and
      cytosolic alkalinization was then explored. Cytosolic alkalinization by monensin
      or NH4Cl enhanced thrombin, ADP, and thimerosal-induced external Ca2+ entry.
      Thimerosal-induced acceleration of external Ca2+ entry was diminished by the
      inhibition of Na+/H+ antiport. Thus external Na+ enhances thrombin activities,
      and cytosolic pH mediates store-regulated external Ca2+ entry. However, Na+/H+
      antiport activation is not essential for agonist-evoked Ca2+ mobilization and
      external Ca2+ entry.

PMID- 7810596
TI  - Protein kinase C inhibits Na(+)-K(+)-2Cl- cotransporter activity in cultured
      rabbit nonpigmented ciliary epithelium.
AB  - We examined the regulation of Na(+)-K(+)-2Cl- transporter activity by protein
      kinase C (PKC) in a cell line derived from rabbit nonpigmented ciliary
      epithelium. Na(+)-K(+)-2Cl- cotransporter activity was measured as the rate of
      bumetanide-sensitive potassium (86Rb) transport. Phorbol 12,13-dibutyrate (PBDu)
      was used to activate PKC. PBDu inhibited bumetanide-sensitive potassium (86Rb)
      uptake, with a half-maximal inhibitory concentration of approximately 0.1 microM.
      The inhibitory effect of PBDu on potassium uptake by the N(+)-K(+)-2Cl-
      cotransporter was abolished by PCK downregulation and diminished by 1-(5
      isoquinolinylsulfonyl)-2-methylpiperazine, a PKC inhibitor. PBDu inhibited Na(+)
      K(+)-2Cl- cotransporter-mediated inward potassium (86Rb) transport by
      approximately 26% in control cells and by 40% in cells pretreated with ouabain.
      PKC activation also reduced the rate of bumetanide-sensitive potassium (86Rb)
      efflux in ouabain-treated cells but not in control (no oubain) cells. PBDu caused
      little change of intracellular sodium, potassium, or chloride, suggesting that an
      alteration of cytoplasmic ion composition is not responsible for the observed
      PBDu-induced changes in the rate of either inward or outward potassium movement
      mediated by the Na(+)-K(+)-2Cl- cotransporter.

PMID- 7810597
TI  - Lactate transport mechanisms at apical and basolateral membranes of bovine
      retinal pigment epithelium.
AB  - The isolated bovine retinal pigment epithelium actively transports lactate from
      the apical to the basal bath. Net short-circuit [14C]lactate flux in 20 mM
      lactate was 0.46 +/- 0.09 mu eq.cm-2.h-1 (n = 8). In open circuit, with a
      physiological lactate gradient, net [14C]lactate flux was 0.66-1.31 mu eq.cm-2.h
      1 (n = 3). Lactate in the apical bath caused intracellular acidifications that
      were saturable, apparently stereospecific, and reduced in magnitude by several H
      lactate cotransport inhibitors. In the basal bath, lactate caused intracellular
      alkalinizations that were dependent on the presence of Na. In short circuit, 20
      mM lactate in both baths reversed the direction of net transepithelial 22Na
      transport from secretion to absorption, suggesting the presence of basolateral Na
      lactate cotransport moving lactate out of the cells. Outwardly directed Na
      lactate cotransport requires a lactate:Na stoichiometry > 1.4:1, consistent with
      the coupled movement of Na, lactate, and net negative charge across the
      basolateral membrane. Intracellular microelectrode recordings showed that basal
      lactate hyperpolarized and apical lactate depolarized the basolateral membrane.
      For lactate absorption, this is a novel arrangement of membrane proteins:luminal
      H-lactate cotransport and serosal electrogenic Na:(n)lactate cotransport. Lactate
      transport across the retinal pigment epithelium may play an important role in
      regulating retinal metabolism and subretinal space volume and composition.

PMID- 7810598
TI  - Serine/threonine kinase activation in human neutrophils: relationship to tyrosine
      phosphorylation.
AB  - Tyrosine phosphorylation is among the earliest responses of neutrophils to
      chemotactic peptides. Tyrosine phosphorylated proteins comigrate with
      serine/threonine kinases of 65 and 72 kDa (PK65 and PK72), which are activated
      concomitantly by the chemoattractants. Studies were designed to test whether
      tyrosine phosphorylation is required for activation of PK65 and PK72.
      Pretreatment of cells with the tyrosine kinase inhibitors erbstatin or genistein
      prevented both phosphotyrosine accumulation and activation of PK65 and PK72. In
      nondenaturing lysates, PK65 and PK72 became spontaneously inactivated in parallel
      with rapid endogenous tyrosine dephosphorylation. Spontaneous dephosphorylation
      and inactivation of PK65 and PK72 were prevented in denatured lysates. Under
      these conditions, dephosphorylation could be induced by exogenous phosphotyrosine
      phosphatase 1B. PK65 and PK72 activation persisted despite virtually complete
      tyrosine dephosphorylation. Moreover, immunoprecipitation experiments indicated
      that PK65 and PK72 are not themselves tyrosine phosphorylated. We concluded that
      tyrosine phosphorylation is a necessary upstream event in the activation of the
      serine/threonine kinases. However, once the posttranslational modification that
      renders PK65 and PK72 active has occurred, tyrosine phosphorylation is no longer
      required for maintenance of their kinase activity.

PMID- 7810599
TI  - Role of redox systems on Fe3+ uptake by transformed human intestinal epithelial
      (Caco-2) cells.
AB  - Caco-2 cells were used as a model of human intestinal epithelium to investigate
      the role of redox systems in transepithelial transport of 59Fe3+. The cells
      reduced Fe3+ present in the apical medium; the reduction was 50% inhibited by
      adriamycin and p-chloromercuribenzoate. Addition of [14C]ascorbate to the
      basolateral medium resulted in accumulation of 14C radioactivity in both cells
      and apical medium; apical radioactivity increased with time and was probably
      caused by paracellular flux. The cells provided Fe3+ reduction capacity to the
      apical incubation medium. Addition of ascorbate to the basolateral medium
      increased this reduction capacity 2-fold and the cellular uptake of 59Fe3+ 1.8
      fold. Adriamycin significantly inhibited both cellular 59Fe uptake and Fe
      transport into the basolateral side. The results indicate that Caco-2 cells
      reduce apical Fe3+ by two parallel mechanisms: by a plasma membrane
      ferrireductase and by the secretion of reductants of either cellular or
      basolateral origin. The data support a model for Fe3+ intestinal absorption in
      which cell-mediated Fe3+ reduction occurs before cellular Fe uptake.

PMID- 7810600
TI  - Aminopyridine inhibition and voltage dependence of K+ currents in smooth muscle
      cells from cerebral arteries.
AB  - Voltage-dependent K+ currents were characterized using the patch-clamp technique
      in smooth muscle cells isolated from rabbit cerebral (basilar) arteries. This
      study focused on the voltage dependence and the pharmacology of these K+
      currents, since this information will be useful for the investigation of the role
      of the voltage-dependent K+ channels in arterial function. Currents through
      Ca(2+)-activated K+ (KCa) channels were minimized by buffering intracellular Ca2+
      to low levels and by blockers (tetraethylammonium and iberiotoxin) of these
      channels. Membrane depolarization increased K+ currents, independent of changes
      in the driving force for K+ movement. With 140 mM internal and external K+,
      activation of K+ currents by membrane depolarization was half maximal at about 
      10 mV and increased as much as e-fold per 11 mV. Inactivation also depended on
      voltage, with a midpoint at -44 mV. 3,4-Diaminopyridine (3,4-DAP),4
      aminopyridine(4-AP),3-amino-pyridine(3-AP), and 2-aminopyridine (2-AP) inhibited
      voltage-dependent K+ currents. At 0 mV, 3,4-DAP, 4-AP, 3-AP, and 2-AP (5 mM)
      inhibited the K+ currents by 84, 66, 36, and 8%, respectively. Phencyclidine (100
      microM) inhibited the current by 53% at 0 mV. Steady-state whole cell currents
      through these channels were measured at physiological membrane potentials. At -40
      mV, 4-AP (5 mM) reduced the steady-state outward current by 2.5 pA. These results
      are consistent with the idea that voltage-dependent K+ channels are involved in
      the regulation of the membrane potential of arterial smooth muscle.

PMID- 7810601
TI  - Effect of series elasticity on delay in development of tension relative to
      stiffness during muscle activation.
AB  - Experimental data have indicated that during activation, the attachment of myosin
      to actin, measured by mechanical stiffness, precedes tension generation by 10-30
      ms. Using computer simulation, we have investigated the effect of a series
      elastic element on the lag between stiffness and tension development during
      muscle activation. Two versions of the two-state cross-bridge model originally
      proposed by Huxley and a three-state model were considered. After simulated
      activation, stiffness and tension increased with rates that were strongly
      dependent on the series elastic strain. In the absence of a series elastic
      element, the rise in stiffness preceded, lagged, or was coincident with the
      increase in tension, depending on the model. For large elastic strains, tension
      lagged stiffness for all models. Lags of 10-30 ms could be obtained with elastic
      strains of 0.3-1% of the muscle length. This is a realistic value in experiments
      without sarcomere length servocontrol, suggesting that series elasticity may be
      an important contributor to the experimentally observed lag between tension and
      stiffness.

PMID- 7810602
TI  - Cl(-)-dependent NH4+ transport mechanisms in medullary thick ascending limb
      cells.
AB  - To characterize Cl(-)-dependent NH4+ transport mechanisms in renal medullary
      thick ascending limb (MTAL), intracellular pH (pHi) and membrane potential (PD)
      were monitored with use of 2',7'-bis(carboxyethyl)- 5(6)-carboxyfluorescein and
      3,3'-dipropylthiadicarbocyanine, respectively, in suspensions of rat MTAL tubules
      in CO2-free media. Exposure of MTAL cells to 4 mM NH4Br caused, after an initial
      cell alkalinization due to NH3 entry, an NH4(+)-induced fall in pHi that was
      approximately 67% less pronounced in Cl(-)-free than in Cl(-)-containing media.
      The following experiments were performed in the presence of 1 microM amiloride to
      block the MTAL NH4+ conductance. When cells were preincubated in a Cl(-)-free
      gluconate medium in which K+ and Cl- conductances are greatly reduced, abrupt
      addition of 100 mN N-methyl-D-glucamine (NMDG)-Cl had no effect on cell PD and
      pHi in the absence of ammonia, but acutely acidified the cells by approximately
      0.2 pH units in the presence of 4 mM NH4Br, which thus indicated nonelectrogenic
      (NMDG-Cl)-dependent NH4+ influx. The latter also occurred in a Cl(-)-free
      thiocyanate medium in which the Cl- conductance was blocked by 0.1 mM
      diphenylamine-2-carboxylate (DPC). An NMDG-Cl- dependent NH4(+)-induced fall in
      pHi was reduced approximately 33% by 10 mM Ba+, approximately 84% by 0.1 mM
      bumetanide, and 100% by 1.5 mM furosemide, whereas 1 mM hydrochlorothiazide had
      no effect; inhibition by Ba+ was observed even in the presence of 0.1 mM
      verapamil added to block both K+ channels and K+/NH4+ antiport.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7810603
TI  - Potassium cotransport at the rat choroid plexus.
AB  - The choroid plexuses are involved in cerebrospinal fluid (CSF) secretion and CSF
      K homeostasis. We examined K transport mechanisms present in the isolated rat
      choroid plexus that may be involved in these functions, predominantly using 86Rb
      as a marker for K. The study demonstrates that there are two primary uptake
      mechanisms. Ouabain-sensitive Na-K-adenosinetriphosphatase and bumetanide
      sensitive cotransport, probably of the Na-K-2Cl form, account for 48 and 46% of
      uptake, respectively. Efflux studies demonstrate that the primary K efflux
      mechanism is also bumetanide-sensitive cotransport with the other major component
      probably being by K channels as it is inhibitable by barium or quinidine. Efflux
      via the cotransporter was not inhibited by R(+)-butylindazone, a KCl cotransport
      inhibitor, but it was enhanced in the presence of ouabain (P < 0.001) or
      increased extracellular Na concentration (P < 0.01). Furthermore, Na efflux was
      bumetanide sensitive (P < 0.05). In all, these data suggest that the efflux
      cotransporter is also of the Na-K-Cl form and that it is the same transporter as
      the influx mechanism operating in both directions. The evidence presented leads
      us to hypothesize that this cotransporter is on the apical membrane of the
      choroid plexus and that it may have a central role in CSF secretion and perhaps
      CSF K homeostasis.

PMID- 7810604
TI  - Migration-associated volume changes in neutrophils facilitate the migratory
      process in vitro.
AB  - Neutrophil granulocytes, while migrating, undergo substantial shape changes from
      the round, resting state to a polarized phenotype. In the present study, we
      monitored cell volume changes in neutrophils migrating toward the chemotactic
      agent N-formyl-methionyl-leucyl-phenylalanine (FMLP) in collagen gels. Neutrophil
      volume was measured through optical sectioning on a confocal microscope and three
      dimensional reconstruction. This method correlated well with Coulter counter
      volume measurements. Migrating neutrophils displayed a significant volume
      increase of 35-60%. The cell swelling appeared to depend on sodium/proton
      antiport activity because it was abrogated by amiloride and dimethyl-amiloride,
      inhibitors of the antiport, and by substitution of sodium in the buffers by
      choline, which is not transported by the antiport. Neutrophils exposed to FMLP
      gradients through impenetrable filters also displayed significant volume changes,
      whereas cells placed on similar filters in homogeneous concentrations of FMLP did
      not. This supports the notion of a differential volume response depending on the
      mode of presentation of the chemotactic agent. The role of volume increase in
      facilitating neutrophil migration was adduced by two lines of evidence: 1)
      hyposmolar swelling enhanced and hyperosmolar shrinking decreased neutrophil
      migration toward FMLP in Boyden chambers and 2) sodium/proton antiport inhibitors
      decreased neutrophil migration; however, this was reversed in hyposmolar buffers,
      which induced a volume increase similar to that seen in normal migrating cells.
      The migration-associated volume increase may be a crucial event for the ability
      of neutrophils to function as the first line of defense at sites of infection.

PMID- 7810605
TI  - K(+)-induced alkalinization in mouse cerebral astrocytes mediated by reversal of
      electrogenic Na(+)-HCO3- cotransport.
AB  - Raising extracellular K+ concentration ([K+]o) induces an alkaline shift of
      intracellular pH (pHi) in astrocytes. The mechanism of this effect was examined
      using the fluorescent pHi indicator 2',7'-bis(carboxyethyl)-5(6)
      carboxyfluorescein in primary cultures of mouse cerebral astrocytes. Raising
      [K+]o from 3 to 12 mM increased pHi by 0.28 pH units in 26 mM HCO(3-)-buffered
      solution. In nominally HCO(3-)-free solution (containing approximately 95 microM
      HCO3-), the alkalinization fell to 0.21 pH units and further to 0.08 pH units on
      removal of atmospheric CO2, suggesting a process with high affinity for HCO3-.
      This effect was Na+ dependent, Cl- independent, and inhibited by 0.5 mM 4,4'
      diisothiocyanostilbene-2,2'-disulfonic acid, indicating the involvement of Na(+)
      HCO3- cotransport. The relationship between pHi and log[K+]o was found to be
      linear and to predict a stoichiometry of at least two HCO3- transported with each
      Na+. After removal of exogenous CO2/HCO3-, the direction of changes in pHi
      elicited by adding 1 mM HCO3- showed that net flux of HCO3- via the Na(+)-HCO3-
      cotransporter was outward at rest and was reversed by depolarization.

PMID- 7810607
TI  - Thyroid hormones modulate both adenosine transport and adenosine A1 receptors in
      rat brain.
AB  - Adenosine transport and adenosine A1 receptors in rat brain are subjected to
      regulation by thyroid hormone levels. The studies were carried out with brain
      stem synaptosomal preparations from rat brain in euthyroid and various
      hypothyroid situations. The maximum velocity of the nitrobenzylthioinosine (NBTI)
      sensitive adenosine transport was 3.3 +/- 0.3 pmol.mg protein-1.s-1 in euthyroid
      rats. The transport in 1-wk thyroidectomized rats was decreased by 45.8% with
      respect to controls. No changes were found in the affinity of euthyroid and
      hypothyroid rats, with the Michaelis-Menten constant values equal to 1.9 +/- 0.9
      and 2.0 +/- 0.5 microM, respectively. The transporter number measured by NBTI
      binding also decreased; the maximum binding capacity (Bmax) was 112.9 +/- 21.9
      and 31.3 +/- 4.1 fmol/mg protein for euthyroid and hypothyroid rats,
      respectively. The adenosine A1 receptors were measured in synaptosomal membrane
      preparations in the presence of 100 microM guanosine-5'-O-3-thiotriphosphate for
      cylopenthyl-1,3-dipropylxanthine 8-[dipropyl 2,3-3H(N)] ([3H]DPCPX) binding. In
      euthyroid rats, the Bmax value was 227.6 +/- 27.6 fmol/mg protein, a significant
      decrease of 23% was obtained in 1-wk hypothyroid rats. In all other thyroid
      situations studied, adenosine transport capacity, adenosine transporter number,
      and adenosine A1 receptor number were restored to control levels.

PMID- 7810606
TI  - Role of protein phosphorylation in control of K flux pathways of trout red blood
      cells.
AB  - The role of protein phosphatases in the regulation of K flux pathways of the
      trout red blood cell has been investigated using the phosphatase inhibitors
      calyculin A and okadaic acid. Both inhibitors completely blocked an oxygenation
      activated Cl-dependent K flux with a 50% inhibitory concentration of 17 and 675
      nmol/l, respectively, but not the hypotonically activated Cl-independent K
      uptake. N-ethylmaleimide (NEM) and staurosporine caused an increase in the Cl
      dependent flux. In both cases preincubation with calyculin A blocked activation
      but, when added during activation, it prevented any further increase with NEM but
      abolished the staurosporine-induced uptake. K uptake that was activated by NEM
      and "clamped" by calyculin A was volume sensitive, indicating a dual influence on
      this pathway. Chelerythrine, a protein kinase inhibitor, activated a Cl
      independent K uptake that was unaffected by calyculin A. It is concluded that
      activation and deactivation of both Cl-dependent and Cl-independent pathways
      require changes in the phosphorylation of an as yet unidentified target
      protein(s), although with different sets of protein kinase and/or phosphatases.
      These observations also suggest a complex model of kinase-phosphatase regulation
      and provide drugs for the pharmacological definition and manipulation of Cl
      dependent and Cl-independent K flux pathways.

PMID- 7810608
TI  - Mechanosensitive modulation of myosin phosphorylation and phosphatidylinositol
      turnover in smooth muscle.
AB  - Myosin light chain phosphorylation and phosphatidylinositol turnover were
      measured at different muscle lengths in bovine tracheal smooth muscle. The
      relationship between myosin phosphorylation and muscle length was linear between
      optimal length (Lo) and 0.1 Lo in both unstimulated and carbachol-activated
      tissues. However, myosin phosphorylation in carbachol-activated tissues was more
      sensitive to changes in muscle length. As a result, suprabasal myosin
      phosphorylation induced by carbachol was significant at Lo but became
      insignificant at 0.1 Lo. Phosphatidylinositol turnover was assayed by measuring
      the formation of myo-[3H]inositol phosphates in unstimulated and carbachol
      activated tissues using the Li+ method. Pairs of time-matched and length-matched
      muscle strips were used for control (unstimulated) and activation by carbachol.
      Phosphatidylinositol turnover in carbachol-activated tissues was more sensitive
      than that in unstimulated tissues to changing length. As a result, suprabasal
      phosphatidylinositol turnover induced by carbachol was significant at Lo but
      became insignificant at 0.1 Lo. These results indicated that myosin
      phosphorylation and phosphatidylinositol turnover mediated by muscarinic receptor
      activation were modulated by the mechanical state of smooth muscle.

PMID- 7810609
TI  - Sources of calcium utilized in cholinergic responses in canine colonic smooth
      muscle.
AB  - Ratiometric fura 2 fluorescence techniques were used to investigate the sources
      of Ca2+ that lead to an increase in cytosolic Ca2+ concentration ([Ca2+]i) and
      the generation of force during cholinergic stimulation of canine colonic circular
      smooth muscle tissues. Acetylcholine (ACh; 1 microM) caused a biphasic increase
      in [Ca2+]i and force. The initial upstroke phase was characterized by an increase
      in [Ca2+]i and a pronounced increase in force. The sustained phase was
      characterized by concurrent oscillations in [Ca2+]i and force (2-3/min) that
      persisted as long as ACh was present. The increase in [Ca2+]i in response to ACh
      was reduced to approximately 30% in the presence of nicardipine (1 microM),
      suggesting that L-type Ca2+ channels contribute to the rise in [Ca2+]i but that
      other sources also contribute. Preincubation in caffeine (10 mM) and ryanodine
      (10 microM) reduced the upstroke phase of the increase in [Ca2+]i and contractile
      responses to ACh, indicating that release of Ca2+ from intracellular stores
      contributes only to the initial cholinergic response. Responses to ACh persisted
      when nicardipine (1 microM) was included after emptying of caffeine-ryanodine
      sensitive stores, suggesting the presence of additional sources of Ca2+. Data
      suggest that cholinergic regulation of [Ca2+]i in colonic smooth muscle occurs by
      a number of parallel pathways. Influx through voltage-dependent Ca2+ channels,
      release of Ca2+ from intracellular stores, and possibly Ca2+ entry through
      additional conductances activated by ACh all contribute to the regulation of
      [Ca2+]i.

PMID- 7810610
TI  - Patterns of tyrosine phosphorylation differ in vascular hypertrophy and
      hyperplasia.
AB  - Vascular smooth muscle cells (VSMC) undergo hypertrophy when exposed to
      thromboxane A2 and hyperplasia when exposed to phorbol 12-myristate 13-acetate
      (PMA) or platelet-derived growth factor (PDGF). Each of these three agonists
      stimulate rapid tyrosine phosphorylation of numerous VSMC proteins. The current
      studies were undertaken to identify proteins that are specifically tyrosine
      phosphorylated in one or the other growth response. All three agonists increased
      the phosphotyrosine content of multiple proteins. In Western analysis of
      phosphotyrosine immunoprecipitates, the hyperplastic agents PDGF and PMA
      increased tyrosine phosphorylation of phospholipase C-gamma 1 (PLC-gamma 1),
      GTPase-activating protein (GAP), and phosphatidylinositol-3-kinase (PI-3-kinase),
      while the hypertrophic agonist thromboxane failed to tyrosine-phosphorylate
      either of these three substrates. Tyrosine kinase inhibition with herbimycin A (5
      microM) prevented agonist-stimulated tyrosine phosphorylation of PLC-gamma 1,
      GAP, and PI-3-kinase. In growth studies, herbimycin A inhibited PMA- and PDGF
      induced hyperplasia but not thromboxane-stimulated hypertrophy. These results
      indicate that tyrosine phosphorylation of PLC-gamma 1, GAP, and PI-3-kinase are
      specific responses for VSMC hyperplasia but not thromboxane-stimulated
      hypertrophy.

PMID- 7810611
TI  - Membrane topology of the epithelial sodium channel in intact cells.
AB  - The highly selective amiloride-sensitive epithelial sodium channel is formed of
      three homologous subunits termed alpha-, beta-, and gamma-rENaC. Each subunit has
      two putative transmembrane domains (M1 and M2), yielding a protein with a large
      (approximately 50 kDa) hydrophilic loop (between M1 and M2) and short hydrophilic
      NH2- and COOH-termini (9 and 10 kDa). All three subunits are glycosylated in a
      cell-free translation assay, demonstrating that they share in vitro a common
      pattern of membrane insertion. The membrane topology of the alpha-rENaC subunit
      in intact cells was studied in Xenopus laevis oocytes. We demonstrate that 1) all
      six potential N-linked glycosylation sites (N190, N259, N320, N339, N424, and
      N538) of the large hydrophilic loop are used in intact cells; 2) the
      glycosylation of alpha-rENaC does not play a significant role in the functional
      expression of the channel; and 3) the two hydrophobic domains M1 (A109-F131) and
      M2 (S588-L612) serve in intact cells as start- and stop-transfer signals,
      respectively. We conclude that alpha-rENaC spans the membrane twice with the
      short NH2- and COOH-terminal ends on the cytoplasmic side and a large hydrophilic
      loop in the extracellular space.

PMID- 7810612
TI  - IKir regulation in murine macrophages: whole cell and perforated patch studies.
AB  - Previous studies have reported that the inwardly rectifying K+ conductance (GKir)
      in macrophages is modulated by intracellular perfusion with inositol 1,4,5
      triphosphate (InsP3), inositol 1,3,4,5-tetrakisphosphate (InsP4), or GTP
      analogues and by exposing cells to macrophage-specific colony-stimulating factor
      (CSF) I. This study uses both conventional whole cell and amphotericin B
      perforated patch studies to investigate GKir modulation in thioglycollate
      elicited mouse peritoneal macrophages (MO). Under whole cell recording conditions
      with 150 mM Cl- in the patch pipette, GKir decreased within 25 min. The GKir
      decrease was slowed by exchanging glutamate for Cl- as the major anion in the
      pipette or by adding guanosine 5'-O-(2-thiodiphosphate) (50 nM) or ATP (0.5 mM)
      to the pipette. Addition of InsP3 or InsP4 to the pipette had no effect on the
      magnitude of GKir or its rate of decrease but activated an outward current in the
      voltage range of +60 to +120 mV in 57% of the cells studied. Thus in murine MO
      GKir may be modulated by G proteins but is unaffected by inositol phosphate
      metabolites, which have been reported to enhance GKir in phorbol 12-myristate 13
      acetate (PMA)-differentiated HL-60 cells. In contrast to whole cell studies,
      perforated patch recordings of murine MO GKir were stable for > 1 h. Perforated
      patch studies demonstrated that murine MO also differ from PMA-differentiated HL
      60 cells in that CSF I had no effect on GKir. Additionally, arachidonic acid,
      PMA, and H2O2, agents implicated in macrophage activation, did not modulate GKir.
      We conclude that GKir regulation in murine MO differs from that reported in PMA
      differentiated HL-60 cells and that although our data suggest that GKir is
      modulated by G protein(s), they differ from the G proteins involved in MO
      responses to CSF I and the other agents tested.

PMID- 7810614
TI  - Protooncogene product, c-mos kinase, is involved in upregulating Na+/H+
      antiporter in Xenopus oocytes.
AB  - Progesterone-stimulated Xenopus laevis oocytes undergo an increase in their
      intracellular pH from 7.3 to 7.7 because of the activation of Na+/H+ antiporters
      in their plasma membrane. Activation of Na+/H+ exchangers (NHE) in other cell
      systems appears to be regulated by phosphorylation of the NHE protein. In the
      current study we demonstrated that cytoplasm taken from steroid-stimulated
      oocytes rapidly induced an increase in intracellular pH when microinjected into
      full-grown stage VI recipient oocytes. The protein within the cytoplasm that
      appears to be responsible for this activity is c-mos kinase. Microinjected pure
      mosxe kinase protein rapidly activated the Na+/H+ exchangers in full-grown
      recipient oocytes. Furthermore, injected mosxe protein rapidly activated the
      Na+/H+ exchangers in smaller progesterone-insensitive stage IV oocytes.
      Therefore, it appears that the protooncogene product, p39 c-mos kinase, which is
      normally synthesized in full-grown stage VI oocytes in response to progesterone
      stimulation, is involved in the upregulation of the Na+/H+ antiporters during
      oocyte meiotic maturation.

PMID- 7810613
TI  - Subcellular distribution of dystrophin in isolated adult and neonatal cardiac
      myocytes.
AB  - The subcellular localization of dystrophin was examined in adult rabbit and rat
      cardiac myocytes with immunofluorescence and at higher resolution with
      immunogold. The aim was to resolve the conflicting reports on the presence of
      dystrophin in the transverse tubules (T tubules) of cardiac muscle and to
      determine its distribution in neonatal myocytes before and during the development
      of the T tubules. Dystrophin was localized to the peripheral sarcolemma and the T
      tubular membrane and was absent from the intercalated disk membranes. In
      addition, dystrophin localization was followed with immunofluorescence in
      developing rabbit myocytes at 4 days, 1 wk, and 1 mo after birth. At 4 days of
      age, T tubules are absent and dystrophin was localized only in the peripheral
      sarcolemma. Dystrophin was present in the developing T tubules at 1 wk and 1 mo.
      These results imply that dystrophin is expressed in the T tubules as soon as they
      develop and confirm the different distribution of dystrophin in the T tubules of
      cardiac and skeletal muscle.

PMID- 7810615
TI  - A new method for the estimation of the components of energy expenditure in
      patients with major trauma.
AB  - The management of critically ill patients would be better understood if the total
      energy expenditure (TEE) and its components are known. To quantify the different
      components of energy expenditure in patients with major trauma, we used a
      technique combining measurements of body composition and oxygen consumption. We
      determined changes in body weight, total body water, total body protein, total
      body potassium, total body fat, and bone mineral content every 5 days over a 10
      day period in a group of nine multiply injured patients. Resting energy
      expenditure was measured by indirect calorimetry (REEm), and a predicted value
      was obtained from total body potassium (REEp). TEE was assessed by adding the
      total calorie intake to the changes in body energy stores, and the activity
      energy expenditure (AEE) was calculated by subtracting REEm from TEE. Mean daily
      values for REEm, REEp, TEE, and AEE were 2,236 +/- 140, 1,683 +/- 82, 3,029 +/-
      276, and 793 +/- 213 kcal/day, respectively, over the 10-day study period.
      Although not statistically significant, the mean AEE was four times smaller for
      the first 5 days of study than for the second 5 days (298 +/- 400 vs. 1,254 +/-
      588 kcal/day). The technique of combining indirect calorimetry and body
      composition measurements offers a new approach to evaluate energy expenditure and
      a new way to study metabolic disorders and therapeutic strategies in critically
      ill patients.

PMID- 7810617
TI  - Metabolic interactions between surplus dietary energy intake and cigarette
      smoking or its cessation.
AB  - Cigarette smoking (CS) alters lipid metabolism and is associated clinically with
      an atherogenic lipid profile. We recently showed that, under controlled eucaloric
      dietary conditions, CS stimulates lipolysis without increasing oxidation of fat
      and that cessation of CS does not result in a rebound tendency to synthesize or
      store fat. We asked here whether the ad libitum intake of surplus dietary energy
      interacts with the metabolic effects of CS or its cessation. Eight male heavy
      smokers were allowed ad libitum food intake in a metabolic ward, 1 wk in CS phase
      and 1 wk in non-CS phase, followed by 4 wk of outpatient non-CS and a repeat 7
      day study. De novo hepatic lipogenesis (DNL), lipolysis, substrate cycling of
      free fatty acids (FFA), hepatic glucose production, and energy expenditure were
      measured by using a multiple stable-isotope infusion protocol and indirect
      calorimetry. Surplus dietary energy intake (> 150% of predicted energy needs)
      occurred in five of eight subjects (2 subjs > 5,500 kcal/day, 3 subjs > 4,000
      kcal/day) with weight gain of 1-4 kg/wk, but with no difference between CS and
      non-CS phases. Acute CS significantly increased (P < 0.05) serum FFA
      concentrations (58%), FFA flux (63%), and glycerol flux (36%); nonsignificantly
      increased extra-adipocyte (hepatic) esterification of FFA (125%, P = 0.10) and
      resting energy expenditure (4.1%, P = 0.22); and did not change adipocyte
      reesterification of FFA or whole body oxidation of fat. Basal metabolic
      parameters (after overnight abstention from CS) did not differ between phases.
      Fractional DNL correlated significantly with excess energy intake (r2 = 0.39) and
      with percentage of total energy needs provided by carbohydrate (r2 = 0.47). The
      absence or presence of CS did not affect the increase in fractional DNL in
      subjects with excess energy intake, however. We conclude that cessation of CS
      does not result in a rebound tendency to synthesis or storage of fat, even in the
      presence of positive short-term energy balance, contrary to previous suggestions.
      Moreover, stimulation of lipolysis by CS does not increase oxidation of fat and
      thereby protect against fat deposition under conditions of surplus energy intake.
      The prevention of weight gain after cessation of CS, whether or not nicotine is
      provided, should focus on energy balance (calorigenesis as well as intake) rather
      than specific alterations in lipid metabolism.

PMID- 7810618
TI  - Adipose tissue metabolism in humans determined by vein catheterization and
      microdialysis techniques.

PMID- 7810619
TI  - Revision of calculations in the doubly labeled water method for measurement of
      energy expenditure in humans.
AB  - In the doubly labeled water (DLW) method for the measurement of energy
      expenditure in humans, the basis of the calculation for CO2 production is the
      difference between the products of the rate constants for the disappearance of
      18O and 2H from body water (KO, and KD, respectively) and the matching isotope
      dilution spaces (NO and ND, respectively). Thus, omitting corrections for isotope
      fractionation, CO2 production = 0.5 (KONO-KDND). In this calculation, it is also
      customary to normalize observed NO and ND values to a fixed value for ND/NO. The
      increasing use of the method has resulted in the generation of substantially more
      information on the normal value for ND/NO than existed at the time the method was
      first developed, and recent work has suggested that revisions of the originally
      used value of 1.03 may now be deemed appropriate. Values of 1.034 or 1.0427 have
      recently been suggested, but when applied in energy expenditure studies these
      estimates would lead to significantly different expenditure measurements. It can,
      however, be shown from published work and direct experimental study that ND/NO
      values are method dependent, and for these reasons the lower revised value of
      1.034 appears to be more acceptable. The possibility that particular populations
      may ultimately be shown to be different from 1.034 should not, however, be
      dismissed entirely, and for this reason we suggest that information derived in
      individual experiments could be used in a Bayesian fashion to generate new ND/NO
      estimates. The appropriate techniques are described.

PMID- 7810616
TI  - Branched-chain amino acids augment ammonia metabolism while attenuating protein
      breakdown during exercise.
AB  - In this study, five men exercised the knee extensor muscles of one leg for 60 min
      (71 +/- 2% maximal work capacity) with and without (control) an oral supplement
      (77 mg/kg) of branched-chain amino acids (BCAA). BCAA supplementation resulted in
      a doubling (P < 0.05) of the arterial BCAA levels before exercise (339 +/- 15 vs.
      822 +/- 86 microM). During the 60 min of exercise, the total release of BCAA was
      68 +/- 93 vs. 816 +/- 198 mumol/kg (P < 0.05) for the BCAA and control trials,
      respectively. The intramuscular BCAA concentrations were higher (P < 0.05) for
      the BCAA trial and remained higher (P < 0.05) throughout exercise. In both
      trials, substantial quantities of NH3 were released, and when NH3 production
      equivalent to IMP accumulation was subtracted the net NH3 production was 1,112 +/
      279 and 1,670 +/- 245 mumol/kg (P < 0.05) for the control and BCAA trials,
      respectively. In contrast, the release of the essential amino acids (EAA) was
      much lower for the BCAA than the control trial (P < 0.05). When the BCAA were
      subtracted from the EAA (EAA-BCAA), the total release of EAA minus BCAA was lower
      (P < 0.05) for the BCAA (531 +/- 70 mumol/kg) than the control (924 +/- 148
      mumol/kg) trial. These data suggest that BCAA supplementation results in
      significantly greater muscle NH3 production during exercise. Furthermore, the
      increased intramuscular and arterial BCAA levels before and during exercise
      result in a suppression of endogenous muscle protein breakdown during exercise.

PMID- 7810620
TI  - Impaired glucose transport in skeletal muscle but normal GLUT-4 tissue
      distribution in glucose-infused rats.
AB  - This study was undertaken to determine if glucose toxicity in normal rats caused
      decreased whole body insulin-stimulated glucose disposal and in vivo impaired
      muscle glucose transport and, if so, whether it was mediated by changes in GLUT-4
      content or tissue distribution. Rats were infused with 50% dextrose for 48 h
      after which they were clamped and injected with 2-deoxy-D-[3H]glucose. Hindlimb
      muscles were removed for measurement of uptake of radioactivity (glucose
      transport) and GLUT-4 levels in total, plasma and internal membrane fractions.
      Dextrose infusions caused significant hyperglycemia [15.5 +/- 1.4 vs. 6.7 +/- 0.3
      (SE) mM], hyperinsulinemia [678 +/- 108 vs. 168 +/- 42 (SE) pM], and depressed
      insulin-mediated whole body glucose disposal [12.8 +/- 2.0 vs. 47.0 +/- 10.6 (SE)
      mg glucose.kg-1.min-1.pmol insulin-1.1(-1) x 10(3)]. Muscle glucose transport
      (ng.min-1.mg tissue-1) was significantly decreased in biceps (4.0 +/- 0.6 vs.
      13.4 +/- 2.5), gastrocnemius (4.6 +/- 1.1 vs. 12.9 +/- 2.2), and plantaris (5.5
      +/- 0.7 vs. 17.5 +/- 3.6) muscles compared with saline-infused rats. The
      difference in the soleus muscle (13.2 +/- 1.6 vs. 19.4 +/- 2.7) did not quite
      reach statistical significance. There were no differences in total, plasma, or
      internal membrane GLUT-4 content between the two groups. It is concluded that
      glucose toxicity causes impaired insulin-stimulated glucose transport, probably
      due to decreased activity of GLUT-4.

PMID- 7810621
TI  - Roles of uptake1 and catechol-O-methyltransferase in removal of circulating
      catecholamines in the rabbit.
AB  - Anesthetized rabbits were simultaneously infused with [3H]norepinephrine (NE),
      [3H]epinephrine (Epi), [3H]dopamine (DA), and [3H]isoproterenol (Iso), and their
      plasma clearances and fractional extractions across the systemic (ERS), as well
      as pulmonary (ERP), circulation were determined before and after blockade of
      uptake1 by desipramine (2 mg/kg). Desipramine reduced the clearance of NE, Epi,
      and DA by 39, 13, and 14%, respectively, but did not affect Iso clearance.
      Similar results were obtained with respect to the effects of desipramine on ERS.
      By contrast, desipramine reduced ERP of NE and DA (which for both amines was
      markedly lower than ERS) by > 70%; its effect on the very low ERP of Epi was not
      determinable. Comparison of the desipramine-sensitive components of ERS and ERP
      indicated that for uptake1 NE was the preferred substrate in the systemic
      circulation and DA was preferred in the pulmonary circulation. In the absence and
      presence of desipramine, catechol-O-methyltransferase inhibition had no effect on
      the clearance of NE, Epi, and DA and decreased Iso clearance by 25%. Hence the
      contribution by uptake1 to the removal of circulating catecholamines depends on
      the type of amine and on whether the systemic or pulmonary circulation is
      considered. Moreover catechol-O-methyltransferase does not appear to contribute
      to the clearance of NE, Epi, and DA but plays a definite role in the removal of
      circulating Iso.

PMID- 7810622
TI  - Altered skeletal pattern of gene expression in response to spaceflight and
      hindlimb elevation.
AB  - Spaceflight leads to osteopenia, in part by inhibiting bone formation. Using an
      animal model (hindlimb elevation) that simulates the weightlessness of
      spaceflight, we and others showed a reversible inhibition of bone formation and
      bone mineralization. In this study, we have measured the mRNA levels of insulin
      like growth factor I (IGF-I), IGF-I receptor (IGF-IR), alkaline phosphatase, and
      osteocalcin in the tibiae of rats flown aboard National Aeronautics and Space
      Administration Shuttle Flight STS-54 and compared the results with those obtained
      from their ground-based controls and from the bones of hindlimb-elevated animals.
      Spaceflight and hindlimb elevation transiently increase the mRNA levels for IGF
      I, IGF-IR, and alkaline phosphatase but decrease the mRNA levels for osteocalcin.
      The changes in osteocalcin and alkaline phosphatase mRNA levels are consistent
      with a shift toward decreased maturation, whereas the rise in IGF-I and IGF-IR
      mRNA levels may indicate a compensatory response to the fall in bone formation.
      We conclude that skeletal unloading during spaceflight or hindlimb elevation
      resets the pattern of gene expression in the osteoblast, giving it a less mature
      profile.

PMID- 7810623
TI  - Ontogeny of the two angiotensin II type 1 receptor subtypes in rats.
AB  - The two subtypes (AT1A and AT1B) of the type 1 (AT1) angiotensin II receptor mRNA
      were localized by in situ hybridization in rat fetal tissues from day 11 to 19 of
      gestation and in the young rat from day 0 to 10 postpartum, by use of 35S-labeled
      cRNA probes. Both subtype mRNAs were present in the kidney and in the adrenal
      gland. Organs such as liver, lung, heart, and undifferentiated mesenchymes
      expressed only AT1A mRNA. In contrast to the adult, only AT1A subtype was
      expressed during fetal and postnatal periods in the pituitary gland. Large blood
      vessels (e.g., aorta and cerebral arteries) expressed exclusively AT1A mRNA
      during fetal stages. The expression of each subtype appears to be differentially
      regulated, in a tissue- and age-specific way. This spatotemporal regulation of
      AT1A and AT1B expression suggests that angiotensin II could act as a
      differentiation factor during organogenesis in addition to its classical role as
      a regulator of the cardiovascular system.

PMID- 7810624
TI  - Calcium uptake by chorioallantoic membrane: effects of vitamins D and K.
AB  - The chorioallantoic membrane (CAM) of birds is an epithelial tissue that actively
      transports large amounts of Ca during embryonic development. In this study the
      effect of vitamins D and K on Ca uptake by the CAM was studied. Four dietary
      treatments were used to produce eggs that are the following: deficient in
      vitamins D and K (-D/-K), sufficient in both (+D/+K), or deficient in one and
      sufficient in the other (-D/+K or +D/-K). Vitamin D-deficient (-D) Japanese quail
      embryos (from hens fed 1,25-dihydroxyvitamin D3) do not hatch because of severe
      Ca deficiency resulting from their inability to obtain Ca from shell, whereas
      vitamin K deficiency results in only 14% reduction in hatchability. The results
      demonstrate that Ca uptake by CAM is vitamin D dependent and only slightly
      vitamin K dependent. Ca-binding activity of CAM extracts was unchanged by vitamin
      K deficiency, and only a small increase was provided by vitamin D treatment.
      Vitamin D stimulated both Ca entry and exist from the chorion cells as indicated
      by the increased accumulated 45Ca in +D embryos. We conclude that vitamin D is
      essential for the utilization of eggshell Ca by the developing embryo and hence
      its survival, suggesting that Ca transport across the CAM is largely a vitamin D
      dependent process.

PMID- 7810625
TI  - Endothelin-1 modulates renin and prolactin release from human decidua by
      different mechanisms.
AB  - Endothelin (ET)-1 stimulates the synthesis and release of renin and inhibits the
      expression of prolactin (PRL) from term human decidual cells. To examine the
      mechanisms by which ET-1 exerts its differential effects on renin and PRL
      expression, we have studied total renin and PRL release from term human decidual
      cells in response to pharmacological agents that affect calcium- and protein
      kinase C-dependent mechanisms. Calcium ionophore A-23187 stimulated basal renin
      release and potentiated ET-1-stimulated renin release but had no effect on basal
      or ET-inhibited PRL release. The calcium channel blocker nifedipine inhibited ET
      1-stimulated renin release but had no effect on PRL release. The protein kinase C
      agonist phorbol 12-myristate 13-acetate (PMA) stimulated basal renin release and
      potentiated the effect of ET-1 on renin release. However, PMA inhibited basal PRL
      release and also enhanced the inhibitory effect of ET-1. The PKC inhibitor
      staurosporine increased basal PRL release and completely reversed the inhibitory
      effect of ET on PRL release. These results indicate that the effects of ET-1 on
      both decidual renin and PRL release are dependent on the activation of protein
      kinase C. However, the effect of ET-1 on renin release appears to be dependent on
      extracellular calcium, whereas the effect on PRL is not influenced by
      extracellular calcium.

PMID- 7810626
TI  - 5 alpha-Dihydrotestosterone partially restores cancellous bone volume in
      osteopenic ovariectomized rats.
AB  - Although androgens are thought to be important for skeletal maintenance in
      females and males, little is known about the mechanisms involved. To investigate
      this question further, we examined the effects of administering 0.01, 0.1, or 1.0
      mg/kg 5 alpha-dihydrotestosterone (DHT) for 60 days on the skeleton of
      ovariectomized rats. Treatment was delayed until 90 days after ovariectomy to
      enable bone loss to stabilize. We found that ovariectomy markedly reduced
      cancellous bone volume of the proximal tibial metaphysis due to a combination of
      loss and thinning of trabeculae. Cancellous bone volume was partially restored by
      all doses of DHT, with trabecular thickness, but not number, returning to that of
      sham-operated animals. DHT also stimulated longitudinal bone growth and endosteal
      and periosteal bone formation and suppressed histomorphometric indexes of
      cancellous bone resorption. This suggests that DHT influences skeletal metabolism
      in osteopenic ovariectomized rats both by stimulating bone formation and
      suppressing resorption, although it is unclear which, if any, of these actions
      predominate at cancellous sites.

PMID- 7810627
TI  - Thyroxine and 3,5,3'-triiodothyronine production, metabolism, and distribution in
      pregnant rat near term.
AB  - In the pregnant rat near term thyroxine (T4) and 3,5,3'-triiodothyronine (T3)
      concentrations are lower in plasma and extrathyroidal tissues, except T3 in the
      brain. To study the changes in T4 and T3 kinetics a bolus injection of [125I]T4
      and [131I]T3 was administered to nonpregnant controls and rats 14 and 19 days
      pregnant. Physiological parameters of the production, interpool transport,
      distribution, and metabolism of T4 and T3 were estimated by means of a three
      compartment model. The production and partition of T4 remained unchanged during
      pregnancy. The total distribution volume of T4 was enlarged. On day 19 the plasma
      clearance rate was doubled, and transport to the fast pool was more than tripled.
      The rate of production of T3 was slightly diminished. The plasma clearance rate
      was increased, but no changes were found in the interpool transport rates. These
      results suggest that in the pregnant rat near term the increased transport of T4
      is responsible for the distribution of the available T4 between the maternal and
      the fetal compartment.

PMID- 7810628
TI  - Role of interleukin-6 and prostaglandins in the effect of monocyte-conditioned
      medium on osteoclast formation.
AB  - There is evidence suggesting some role of mononuclear cells at the resorptive
      site in bone remodeling. The possibility was therefore postulated that these
      cells might provide some signal for osteoclast formation. We examined the effects
      of human monocyte-conditioned medium (CM) on the formation of osteoclast-like
      cells from hemopoietic blast cells in the absence of stromal cells and
      unfractionated bone cells in the presence of stromal cells. In both culture
      systems, the osteoclast-like cell formation induced by 1,25-dihydroxyvitamin D3
      [1,25(OH)2D3] or human parathyroid hormone (PTH)-(1-34) was significantly
      inhibited by adding 20% CM. The effects of monocyte-derived local regulators of
      bone turnover on osteoclast-like cell formation induced by 1,25(OH)2D3 or PTH
      were determined. Interleukin-6 (IL-6) inhibited osteoclast-like cell formation in
      both culture systems, whereas prostaglandin (PG) E2 significantly inhibited the
      formation only in the hemopoietic blast cell culture. The inhibitory effect of CM
      on osteoclast-like cell formation from hemopoietic blast cells was not observed
      when CM was prepared from monocytes pretreated with indomethacin. The inhibitory
      effect of CM and IL-6 on osteoclast-like cell formation in both culture systems
      was blocked by adding neutralizing IL-6 antibody. The present study demonstrated
      that CM inhibited osteoclast-like cell formation induced by 1,25(OH)2D3 and PTH
      presumably through the action of local regulators of bone turnover, such as IL-6
      and PG. Our findings thus provide additional evidence that mononuclear cells play
      an important role at the resorptive site in bone remodeling.

PMID- 7810629
TI  - Effect of hyperinsulinemia and hyperaminoacidemia on muscle and liver protein
      synthesis in lactating goats.
AB  - The experiment was carried out to clarify the roles of insulin and amino acids on
      protein synthesis in fed lactating goats (30 days postpartum). Protein synthesis
      in the liver and various skeletal muscles was assessed after an intravenous
      injection of a large dose of unlabeled valine containing a tracer dose of L
      [2,3,4-3H]valine. The animals were divided into three groups. Group I was infused
      with insulin (1.7 mumol/min) for 2.5 h under glucose, potassium, and amino acid
      replacement. Group A was infused with an amino acid mixture to create stable
      hyperaminoacidemia for 2.5 h. Group C animals were controls. The fractional
      synthesis rates (FSR) were 31.5 +/- 2.2, 6.5 +/- 0.4, 4.3 +/- 0.8, 4.0 +/- 1.2,
      3.9 +/- 1.2, and 3.6 +/- 0.4%/day (SD) in liver, masseter, diaphragm, anconeus,
      semitendinosus, and longissimus dorsi, respectively, for group C. Neither
      hyperinsulinemia in group I nor hyperaminoacidemia in group A had not affected by
      hyperinsulinemia but was stimulated by hyperaminoacidemia (+30%, P < 0.05). In
      contrast to previous experiments in which a labeled amino acid was constantly
      infused, this study revealed a stimulating effect of amino acids on protein
      synthesis in the liver but not in skeletal muscles. As previously observed in
      studies with the constant-infusion method, insulin had no effect on protein
      synthesis.

PMID- 7810630
TI  - Acute alcohol administration attenuates insulin-mediated glucose use by skeletal
      muscle.
AB  - The aim of the present work was to test the effect of acute in vivo alcohol
      administration (180-190 mg/dl plasma for 3 h) on glucose utilization by tissues
      under basal conditions or after a hyperinsulinemic (100-130 microU/ml) euglycemic
      clamp in fasted rats. In vivo glucose use by individual tissues was assessed by
      the tracer 2-deoxy-D-glucose technique. Alcohol administration to saline-infused
      rats markedly inhibited glucose use by skeletal muscles, including the soleus,
      white and red quadriceps, and gastrocnemius, as well as by the heart. Ethanol
      infusion, however, had no effect on glucose use by the diaphragm, lung, liver,
      skin, ileum, brain, and adipose tissue. The insulin-stimulated glucose use was
      also inhibited by alcohol selectively in the muscles, with no effect on other
      tissues tested, except a moderate inhibition in the brain. Ethanol inhibited
      muscle glucose use by an average of approximately 50% under both basal and
      insulin-stimulated conditions. However, because insulin treatment more than
      doubled basal glucose use by these muscles, the 50% inhibition by ethanol
      treatment represents a greater inhibition of absolute glucose use under insulin
      stimulated rather than under basal conditions. Our data demonstrate that acute
      alcohol intake attenuates basal and hormone-induced glucose utilization in a
      tissue-specific fashion. The inhibitory effect of alcohol on skeletal muscle
      glucose use could contribute to the previously observed decreased glucose
      recycling in humans after acute alcohol intake.

PMID- 7810631
TI  - Regional variations in metabolic responses of white adipose tissue to food
      restriction.
AB  - The effects of food restriction (limited access to food for 2 h/day for 10 days)
      on lipoprotein lipase (LPL) activities and rates of fatty acid synthesis and
      glucose utilization in vivo in two superficial (interscapular and subcutaneous)
      and three deep abdominal white adipose tissue depots (parametrial, perirenal, and
      mesenteric) of adult female Wistar rats were examined before and at 2 h after a
      standard laboratory diet meal (5 g). Fasting LPL activities in perirenal (1.6
      fold), mesenteric (5.9-fold), and subcutaneous (2.7-fold) adipose tissue, when
      expressed per unit of delipidated tissue, were increased in response to food
      restriction. This effect was retained (but not enhanced) after the meal. In
      contrast, muscle LPL activities were either unchanged or suppressed by food
      restriction. Stimulation of adipose tissue fatty acid synthesis and glucose
      utilization evoked by feeding in control rats was greatly enhanced by prior food
      restriction. There was no relationship between anatomical location and presence
      or absence of the response of adipose tissue LPL activity to food restriction,
      but the effect of food restriction to enhance the responses of fatty acid
      synthesis and glucose utilization to a meal was more marked in perirenal and
      parametrial adipose tissue than in the more superficial depots. The results thus
      demonstrate regional specificity in the response of adipose tissue functions to
      food restriction.

PMID- 7810633
TI  - Leucine kinetics are different during feeding with whole protein or
      oligopeptides.
AB  - To determine if the molecular form of nitrogen intake affects protein metabolism
      during feeding, 12 normal volunteers received, by continuous nasogastric
      infusion, a protein or a peptide-based diet. Leucine kinetics (oral [13C]leucine
      and intravenous [2H3]leucine) were measured during the following three
      consecutive periods: first carbohydrates and lipids alone, then with either whole
      casein or oligopeptides in a randomized crossover design, with these two latter
      periods being isonitrogenous, isocaloric, and of identical amino acid
      compositions. Leucine concentration, turnover, oxidation, and nonoxidative
      disposal increased during nitrogen administration (all P < 0.01) and were higher
      with oligopeptides than with casein (242 +/- 44 vs. 188 +/- 31 mumol/l; 2.75 +/-
      0.45 vs. 2.23 +/- 0.31; 1.14 +/- 0.19 vs. 0.82 +/- 0.22 mumol.kg-1.min-1, all P <
      0.001; 1.64 +/- 0.32 vs. 1.44 +/- 0.33 mumol.kg-1.min-1, P < 0.05, respectively).
      Endogenous leucine production was less inhibited by oligopeptides than by casein
      (0.82 +/- 0.41 vs. 0.38 +/- 0.31 mumol.kg-1.min-1, P < 0.001), whereas splanchnic
      extractions were similar. Finally, leucine balance was more positive with casein
      than with oligopeptides (P < 0.001). In conclusion, the response of leucine
      kinetics to feeding is modified by the molecular form of nitrogen intake, with
      the oligopeptides inducing a higher oxidation and protein synthesis and a lesser
      inhibition of protein breakdown.

PMID- 7810632
TI  - Kinetic analysis of glycogen synthase and PDC in cirrhotic rat liver and skeletal
      muscle.
AB  - Glycogen synthase (GS) and pyruvate dehydrogenase complex (PDC) were kinetically
      analyzed in the liver and skeletal muscle of fasted and refed rats with
      thioacetamide-induced cirrhosis of the liver. In control rats, refeeding induced
      a 54% decrease in the A0.5 for glucose 6-phosphate (G-6-P) of hepatic GS (P <
      0.001), reflecting allosteric activation of the enzyme. In skeletal muscle the
      A0.5 for G-6-P did not change after refeeding, whereas the activity ratio
      increased by 56% (P < 0.01), indicating a greater percentage of the active G-6-P
      independent form of the enzyme. In cirrhotic rats, neither the A0.5 for G-6-P of
      liver GS nor the activity ratio of muscle GS was influenced by refeeding.
      Consequently, glycogen replenishment was significantly impaired both in the liver
      (2.56 +/- 0.2 vs. 5.11 +/- 0.4 g/100 g; P < 0.001) and skeletal muscle (0.45 +/-
      0.01 vs. 0.52 +/- 0.02 g/100 g; P < 0.01). Refeeding increased the percentage of
      the active form of hepatic PDC both in control (+88%; P < 0.01) and cirrhotic
      rats (+91%; P < 0.001). In the latter, however, the rates of total and active PDC
      were significantly lower than in controls [-44% and -40% in fasted (P < 0.005)
      and refed (P < 0.005) rats, respectively]. Muscle PDC kinetics (both maximal
      velocity and Michaelis constant) and the percent active form were identical in
      cirrhotic and control rats, regardless of the nutritional state.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7810634
TI  - Changes in regional protein synthesis in rat brain and pituitary after systemic
      interleukin-1 beta administration.
AB  - A convenient and sensitive method has been developed for measuring changes in
      protein synthesis in discrete areas of the brain and pituitary of conscious
      freely moving rats. A single injection of high-concentration low-specific
      activity L-[35S]methionine is given to flood amino acid precursor pools, thereby
      equalizing the specific activity of the L-[35S]methionine throughout the tissue.
      Unincorporated L-[35S]methionine is removed from cryostat sections by treatment
      with perchloric acid (2%) before quantitative autoradiography. The sensitivity of
      this technique is demonstrated by the detection of changes in protein synthesis
      in regions of the brain and pituitary after systemic administration of
      interleukin-1 beta, a cytokine that has centrally mediated effects but which is
      not thought to cross the blood-brain barrier. Areas of the brain found to exhibit
      significant increases in protein synthesis were the subfornical organ, the
      choroid plexus, the medial habenular, the dentate gyrus, and the anterior and
      posterior lobes of the pituitary. In the brain, the cingulate cortex and the
      pineal gland showed significant decreases in the rate of protein synthesis.

PMID- 7810635
TI  - Mineralocorticoid antagonist inhibits stress-induced blood pressure response
      after repeated daily warming.
AB  - We report here that with a direct method for measurement of cardiovascular
      parameters in conscious rats, intracerebroventricular administration of the
      mineralocorticoid receptor (MR) antagonist RU-28318 (100 ng) reduces the blood
      pressure, heart rate, and the corticosterone response to a brief restraint
      stress, provided the rats were previously subjected to a daily 30-min exposure to
      32 degrees C for 2 wk. The daily exposure to warming and restraint stress are
      applied identically to the training procedure required for indirect blood
      pressure measurement using the tail-cuff method. The basal arterial pressure is
      not affected by the MR antagonist. The effect of the MR antagonist on the stress
      induced pressor response develops with a delay of several hours in the
      normotensive rats. The corticosterone response to daily warming and stress is
      also attenuated by the intracerebroventricular infusion of MR antagonist but with
      shorter onset and shorter duration. The findings suggest that conditioning to
      daily warming and stress imposes mineralocorticoid dependency of the pressor
      response, which involves MR functioning in brain.

PMID- 7810636
TI  - Central effects of mineralocorticoid antagonist RU-28318 on blood pressure of
      DOCA-salt hypertensive rats.
AB  - The role of brain mineralocorticoid receptor (MR) sites in the pathogenesis of
      mineralocorticoid hypertension was studied after an intracerebroventricular
      injection of the MR antagonist RU-28318. Male Wistar rats received subcutaneously
      implanted deoxycorticosterone acetate (DOCA) pellets and were maintained on 0.9%
      saline as drinking solution. Under these conditions hypertension developed in
      approximately 5 wk as assessed in conscious rats by means of the tail-cuff
      technique. During the development of this hypertension (after 3 wk of DOCA-salt
      treatment) a single intracerebroventricular injection of the specific MR
      antagonist RU-28318 reduced systolic blood pressure (SBP) as measured with the
      tail-cuff method. A decrease in SBP was observed 2-24 h after this
      intracerebroventricular injection, with the lowest SBP values occurring at 8 h.
      In these animals (3 wk after DOCA implantation) continuous direct blood pressure
      recording via chronic cannulation revealed, on the day of the
      intracerebroventricular injection of RU-28318, a slight increase in arterial
      pressure during the light phase, followed by a decrease during the dark phase. In
      the established hypertensive rats (5 wk after DOCA RU-28318 on the arterial
      pressure or heart rate was detectable. It is concluded that central MR blockade
      during the development of the DOCA-salt hypertension reduces blood pressure
      within 24 h assessed with 1) the indirect method at certain time points after
      exposure to warming and stress and 2) the direct method during the dark phase of
      the diurnal cycle.

PMID- 7810637
TI  - Fat metabolism during low-intensity exercise in endurance-trained and untrained
      men.
AB  - Whole body lipid kinetics were evaluated during basal resting conditions, 4 h of
      treadmill exercise eliciting an oxygen uptake of 20 ml.kg-1.min-1, and 1 h of
      recovery in five untrained and five endurance-trained men. Glycerol and free
      fatty acid (FFA) rate of appearance (Ra) values in plasma were determined by
      infusing [2H5]glycerol and [1-13C]palmitate, respectively, and lipid oxidation
      was determined by indirect calorimetry. The lipolytic response to 4 h of
      exercise, expressed as the average glycerol and FFA Ra values, was similar in
      both trained (9.85 +/- 1.02 and 24.64 +/- 3.76 mumol.kg-1.min-1, respectively)
      and untrained subjects (11.29 +/- 0.99 and 24.13 +/- 0.39 mumol.kg-1.min-1,
      respectively). However, mean triglyceride oxidation was greater during exercise
      in the trained than in the untrained group (7.51 +/- 0.26 and 5.67 +/- 0.51
      mumol.kg-1.min-1, respectively; P < 0.001). During recovery, glycerol and FFA Ra
      values decreased more rapidly in trained than in untrained subjects. We conclude
      that highly trained male endurance runners use more fat as a fuel during low
      intensity exercise than do untrained healthy men despite similar rates of
      lipolysis and FFA uptake from plasma. Therefore, the increase in fat oxidation
      must be related to an increased percentage of FFA uptake oxidized, a greater
      contribution from intramuscular triglyceride stores, or both. Additionally, lipid
      kinetics return to baseline more rapidly in trained than in untrained subjects
      after completing an exercise bout of the same absolute intensity.

PMID- 7810638
TI  - Effect of antilipolysis on heart and skeletal muscle glucose uptake in overnight
      fasted humans.
AB  - We quantitated how lowering of free fatty acid (FFA) by an antilipolytic agent
      (acipimox) in the fasting state changes glucose uptake in heart and skeletal
      muscles. Glucose uptake in these tissues was measured two times in seven normal
      subjects, once after acipimox and once after placebo, using positron emission
      tomography-derived [18F]fluoro-2-deoxy-D-glucose kinetics. Plasma glucose and
      insulin remained at their fasting concentrations in both studies. Fasting FFA
      concentrations were 60% lower after acipimox (238 +/- 39) than placebo (645 +/-
      78 mumol/l, P < 0.001). Glucose uptake increased 6 +/- 2-fold in the heart by
      acipimox (344 +/- 49 vs. 108 +/- 40 mumol.kg muscle-1.min-1, P < 0.002) and 1.5
      fold in arm muscles (27.7 +/- 2.6 vs. 18.6 +/- 1.2 mumol.kg muscle-1.min-1, P <
      0.02). Heart (r = -0.93, P < 0.001) and arm (r = -0.82, P < 0.001) glucose
      uptakes were inversely related to serum FFA. We conclude that serum FFA are
      inversely related to glucose uptake in heart and arm skeletal muscles after an
      overnight fast. These data indicate that compensatory glycogenolysis, although it
      may occur, does not prevent operation of the glucose-FFA cycle under fasting
      conditions.

PMID- 7810639
TI  - Sympathetically and nonsympathetically mediated onset of excess fat deposition in
      Zucker rats.
AB  - To evaluate whether a low sympathetic activity is essential for the onset of
      Zucker rat obesity, we artificially reared fa/fa and Fa/fa littermates from 4
      days of age with identical amounts of milk containing norepinephrine (NE). The NE
      concentration was adjusted to keep the mass-specific metabolic rate (MR) roughly
      either 100 or 50% above its thermoneutral level. At both doses, no genotype
      difference in total MR occurred before day 16, but between 16 and 21 days of age,
      total MR of fa/fa pups was 10% less than that of their Fa/fa littermates. The 21
      day-old fa/fa pups had approximately 1 g more body fat than their lean
      littermates, and this was energetically accounted for to 50-80% by their lower MR
      and to 10-25% by the reduced growth of their fat-free dry mass. We conclude that
      factors not dependent on decreased sympathetic outflow trigger the onset of
      excess fat deposition in the 3rd postnatal wk, even if sympathetic activity was
      high throughout the previous weeks during which excessive fat deposition is
      mainly dependent on decreased thermoregulatory thermogenesis.

PMID- 7810640
TI  - cAPK mediates placental renin secretion stimulated by beta-adrenoceptor
      activation.
AB  - Previous studies have indicated that activation of placental beta-adrenoceptors
      stimulates renin secretion, whereas basal secretion is extremely low. This
      response is potentiated by inhibition of types III and IV phosphodiesterases,
      implicating a role for adenosine 3',5'-cyclic monophosphate (cAMP). Described are
      experiments aimed at defining the regulatory influence of cAMP and cAMP-dependent
      protein kinase (cAPK) isotypes in renin secretion. Human placental explants were
      cultured with dobutamine, a beta 1-agonist, and cAPK activity, renin, and cAMP
      concentrations were determined. After 48 h of incubation, media concentrations of
      renin and cAMP increased and were positively correlated. Tissue cAPK activity was
      positively correlated with renin secretion associated with dobutamine. Renin
      secretion was measured in response to substituted cAMP analogues selective for a
      unique cAMP binding site (site A or B) for cAPK regulatory subunits. A fivefold
      stimulation of renin secretion by the type II site B activators occurred, whereas
      a threefold increase was seen with a type I site B analogue. Site A-selective
      analogues for cAPK types I and II produced no stimulation. Dobutamine-induced
      renin secretion was attenuated by selective inhibitors of cAPK regulatory and
      catalytic subunits. These findings indicate that placental renin secretion
      associated with beta-adrenoceptor activation is correlated with cAMP generation
      and mediated predominantly by the type II isoform of cAPK.

PMID- 7810641
TI  - Calcitriol therapy and calcium-regulated PTH secretion in patients with secondary
      hyperparathyroidism.
AB  - Calcitriol lowers serum parathyroid hormone (PTH) levels in patients with
      secondary hyperparathyroidism, but its effect on calcium-regulated PTH release
      remains controversial. Thus 11 patients with secondary hyperparathyroidism
      underwent dynamic tests of parathyroid function before and after 4 mo of
      intermittent calcitriol therapy. Serum calcitriol levels rose from 8 +/- 1 to 55
      +/- 9 (SE) pg/ml, P < 0.01, serum total and ionized calcium levels increased, and
      serum PTH levels decreased from 584 +/- 154 to 154 +/- 31 pg/ml, P < 0.05. The
      maximum increase in serum PTH during hypocalcemia did not differ before (248 +/-
      78 pg/ml) or after (280 +/- 100 pg/ml) treatment, but the increase in PTH,
      expressed as a percentage of preinfusion values, was greater after treatment (329
      +/- 73 vs. 132 +/- 10%, P < 0.05). The decreases in serum PTH during calcium
      infusions did not differ before (70 +/- 5%) or after (73 +/- 5%) therapy, and the
      set point for PTH release did not change (1.20 +/- 0.03 vs. 1.23 +/- 0.01 mmol/l,
      not significant). Calcitriol modifies PTH secretion during hypocalcemia in
      secondary hyperparathyroidism without affecting the set point for PTH release;
      although calcitriol lowers serum PTH levels, it may also restore the secretory
      reserve of hyperplastic parathyroid tissues during hypocalcemia.

PMID- 7810642
TI  - Post-GLUT-2 defects in beta-cells of non-insulin-dependent diabetic obese rats.
AB  - Zucker diabetic fatty (ZDF) rats develop non-insulin-dependent diabetes mellitus
      concomitantly with loss of glucose responsiveness and GLUT-2, the high-Michaelis
      constant glucose transporter of beta-cells. To determine the integrity of beta
      cell glucose metabolism distal to the level of glucose transport and
      phosphorylation, we examined the insulin responses of isolated pancreata to 5,
      10, and 20 mM D-glyceraldehyde and monomethylsuccinate, as well as to glucose.
      The insulin response of diabetic pancreata to glucose was 90% below the response
      prior to the onset of diabetes, whereas the responses to glyceraldehyde and
      succinate had declined to 65 and 44%, respectively, below the prediabetic
      responses. D-[14C]glyceraldehyde oxidation by diabetic islets was 74% below that
      of islets from lean nondiabetic controls. We conclude that 1) the insulin
      responses to glyceraldehyde and monomethylsuccinate, as well as to glucose, are
      impaired in the diabetes of ZDF rats and 2) the impairment of the glucose
      response was greater than that of the glyceraldehyde response, which was, in
      turn, greater than that of the monomethylsuccinate response; this decrescendo
      pattern of impairment is consistent with defects at multiple sites in glucose
      metabolism; if the defect were entirely due to a postmetabolic signaling defect,
      the impairment to glucose and its metabolites should be comparable.

PMID- 7810643
TI  - Effects of a fish oil-lard diet on rat plasma lipoproteins, liver FAS, and
      lipolytic enzymes.
AB  - The effects of a fish oil concentrate on blood lipids and lipoproteins were
      examined in relation to their effects on liver fatty acid synthase (FAS), 3
      hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, adipose tissue lipoprotein
      lipase (LPL), and hepatic triglyceride lipase (H-TGL). For 15 days, 2-mo-old rats
      were fed a control diet (10% of calories from fat, 4% fat by weight) or diets
      with 50% of calories (25% wt/wt) provided by lard, lard and fish oil calories
      (35%/15%), or lard and corn oil (35%/15%). The high-lard diet increased plasma
      chylomicron and liver triglycerides. The high-lard diet greatly decreased FAS,
      HMG-CoA reductase, and LPL activities; it also reduced H-TGL activity. Compared
      with the lard diet, the lard-fish oil diet decreased plasma TG by drastically
      lowering chylomicron (4-fold, P < 0.001) and very-low-density lipoprotein levels
      (P < 0.001). It also reduced high-density lipoprotein levels. The lard-fish oil
      diet prevented hepatic triglyceride accumulation and decreased FAS activity and
      mass by 3.5-fold (P < 0.001) but did not further decrease HMG-CoA reductase
      activity. Adipose tissue LPL activity was 2.5-fold (P < 0.001) higher with the
      lard-fish oil diet than with the lard diet, and H-TGL activity decreased
      significantly (-32%, P < 0.01), despite unaltered levels of H-TGL mRNA. These
      effects were significant with only 10% fish oil concentrate in the lard diet.
      They were not observed with the lard-corn oil diet.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7810644
TI  - Effects of thyroid hormone deiodination on regulation of thyroid axis in
      undernourished rats.
AB  - The possible influence of hypothalamic and pituitary 5'-deiodinase II (5'-D-II)
      activity and 3,5,3'-triiodothyronine (T3) content on the modulation of thyroid
      stimulating hormone (TSH) synthesis was studied. 1) Alterations in 5'-D-II
      activity and hypothalamic and pituitary T3 content produced by undernutrition
      were observed in fetal (21 days) and neonatal rats vs. controls. 2) After
      thyroidectomy, plasma TSH increased in both populations, undernourished and
      control, but pituitary TSH increased only in the former and not in the latter.
      The results obtained by giving small doses of thyroxine (T4; 0.5 micrograms/100 g
      body wt) to intact and thyroidectomized rats suggest a lower inhibitory effect by
      T4 on the pituitary in undernourished than in control rats. Although hypothalamic
      and pituitary 5'-D-II activity increased in both groups after thyroidectomy, the
      percentage increase was lower in undernourished vs. control rats, resulting in
      lower overall T3 content in tissues from undernourished animals. These studies on
      thyroid axis regulation show the in vivo regulation of TSH synthesis by
      hypothalamic and pituitary 5'-D-II activity and T3 content.

PMID- 7810645
TI  - Modulation of growth factor incorporation into ECM of human osteoblast-like cells
      in vitro by 17 beta-estradiol.
AB  - Human fetal osteoblast-like cells formed a regular multilayered structure in
      vitro with an extensive collagen-based extracellular matrix. With colloidal gold
      immunocytochemistry, labels for alkaline phosphatase and osteocalcin were
      distributed in a relatively diffuse pattern, in contrast to the bone growth
      factors, insulin-like growth factors I and II (IGF-I and IGF-II), transforming
      growth factor-beta 1 (TGF-beta 1), and basic fibroblast growth factor, which were
      colocalized in the collagenous matrix of the multilayer. The inclusion of 17 beta
      estradiol (10(-11) to 10(-9) M) in the culture medium increased multilayer
      depths, increased labeling for IGF-I, IGF-II, and TGF-beta 1, and resulted in
      earlier detection of TGF-beta 1 label. In contrast, the increase in multilayer
      depth resulting from treatment with human platelets, an exogenous source of
      growth factors, was not accompanied by an increase in matrix IGF-I, IGF-II, or
      TGF-beta 1 label, suggesting a particular effect of estradiol to facilitate this
      process. Because growth factors in bone matrix may act as coupling agents when
      released during resorption, reduced growth factor incorporation in the presence
      of reduced sex steroid concentrations may lead to uncoupling of resorption and
      subsequent formation.

PMID- 7810646
TI  - Na-K-Cl cotransport in villus and crypt cells from rat duodenum.
AB  - The aim of the present study was to examine the possibility that Cl- uptake into
      both villus and crypt epithelial cells of rat duodenum occurs via an
      electroneutral Na-K-Cl coupled-transport mechanism. Sheets of villus cells and
      whole crypts were isolated using a Ca2+ chelation technique combined with
      continuous vibration at low temperatures. Structurally intact, viable epithelia
      from defined regions along the villus-crypt axis were produced. Uptake of 86Rb+
      (as a proxy for K+) into both villus and crypt cells appeared to depend on a
      coupled process, as evidenced by the inhibition of 86Rb+ uptake by bumetanide and
      by the removal of either Na+ or Cl- from the bathing media. We report an improved
      method of isolation of viable enterocytes from defined regions along the villus
      crypt axis. We demonstrate the presence of Na-K-Cl cotransport in both villus and
      crypt duodenal enterocytes.

PMID- 7810647
TI  - Apical acidification induces paracellular injury in canine gastric mucosal
      monolayers.
AB  - We used primary monolayer cultures of enzyme-dispersed canine oxyntic mucosal
      cells mounted in Ussing chambers to characterize the apical barrier to H+.
      [3H]mannitol flux (MF) and [14C]inulin flux (IF) were used as size probes for
      tight junctions. Apical H+ produced a three-phase effect. In phase 1, as the
      apical pH was decreased from 7 to about 2.5, resistance (R) increased, but short
      circuit current (Isc) did not change. In phase 2, an increased paracellular
      permeability developed at pH below 2.5-1.7, evidenced by decreased R and
      increased MF but not IF. Size sieving and monolayer integrity were preserved, and
      this paracellular leak was either fully reversed or stabilized by apical
      neutralization, depending on the duration of the paracellular leak. In phase 3,
      after sustained exposure to an apical pH below approximately 2, transepithelial
      integrity was lost; R decreased to fluid R, and both MF and IF increased.
      Basolateral acidification below pH 5.5 produced rapid monolayer disruption. Low
      concentrations of cytochalasin D (CD) decreased R and increased MF but not IF;
      apical acidification to pH 4 after CD increased R and decreased the MF,
      indicating reduced paracellular permeability by apical H+. Apical amiloride did
      not alter Isc; however, after 48 h of treatment with hydrocortisone and insulin,
      an amiloride-sensitive Isc component became evident. Our data indicate that the
      increase in R observed with apical acidification reflects decreased paracellular
      permeability and that the earliest injury with apical acidification is a
      selective paracellular leak.

PMID- 7810648
TI  - Inhibition of ornithine decarboxylase does not prevent intestinal smooth muscle
      hyperplasia in the rat.
AB  - The objective of this research is to examine the relationship between intestinal
      smooth muscle cell proliferation and polyamine metabolism. Proliferation of
      muscle is induced by serosal application of benzyldimethyltetradecylammonium
      chloride (BAC) to a segment of rat jejunum. This treatment destroys all of the
      longitudinal muscle, one-half of the circular muscle, and the myenteric and
      extrinsic nerves. The remaining muscle cells undergo mitosis and, by 15 days, the
      number of muscle cells is increased in both the longitudinal and circular muscle
      layers. Within 12 h after BAC treatment, there is an increase in the activity of
      ornithine decarboxylase (ODC) that returns to preinjury levels by 4 days. The
      smooth muscle content of the three polyamines putrescine, spermidine, and
      spermine is increased 6 h after injury, returning to preinjury levels within 1
      day. DL-alpha-Difluoromethylornithine (DFMO), an irreversible inhibitor of ODC,
      prevents the transient increases in both ODC activity and the three polyamines in
      the smooth muscle. In addition to preventing the transient increases in the three
      polyamines, DMFO has different effects on smooth muscle content of putrescine,
      spermidine, and spermine. Putrescine content is permanently depleted by DFMO.
      Spermidine and spermine content is initially decreased within 24 h by DFMO
      administration. In contrast to the persistent depletion of putrescine by DFMO,
      spermidine and spermine return to preinjury levels by 2 days. The maximal peak in
      DNA synthesis occurs 2 days after injury. In DFMO-administered animals, the
      maximal DNA synthesis occurs 5 days after injury. The increases in smooth muscle
      wet weight and DNA content 15 days after injury are not affected by
      DFMO.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7810649
TI  - Evidence that hepatic triglycerides provide acylglycerides for synthesis of bile
      phosphatidylcholines.
AB  - To determine the biochemical origin of bile phosphatidylcholines (PCs), rat liver
      perfusions with 16:1 fatty acid (FA) and [3H]glycerol were performed to generate
      novel radiolabeled bile and liver PCs and their hepatic glyceride precursors.
      Results showed total equilibration of bile and liver 16:1-16:1 PC when the
      specific activity of precursor glycerol-3-phosphate was kept constant. However,
      when the specific activity of glycerol-3-phosphate decreased during the labeling
      period and during a prolonged chase period with 17:1 FA and nonradiolabeled
      glycerol, the specific activity of bile 16:1-16:1 PC was appreciably higher than
      this same PC in the liver and during the chase period was even higher than its
      hepatic 16:1-16:1 acylglycerol precursors, phosphatidic acid and diglyceride.
      During the chase period with 17:1 FA, new radiolabeled 16:1-17:1 PC was formed,
      and again the specific activity of this PC in bile was greater than this PC and
      16:1-17:1 phosphatidic acid and diglyceride in the liver. Only the specific
      activity of liver 16:1-16:1-(FA) triglyceride equaled or was high enough to
      support the formation of new bile 16:1-16:1 PC. These studies indicate that bile
      PCs do not directly derive from preexisting hepatic PCs or by de novo synthesis
      through phosphatidic acids and diglycerides, but likely originate by remodeling
      from a pool of hepatic triglycerides.

PMID- 7810650
TI  - Glutamine-enriched enteral diet increases splanchnic blood flow in the rat.
AB  - The hemodynamic consequences of glutamine (Gln)-enriched nutrition have not been
      investigated. This study investigates the effects of a Gln-enriched enteral diet
      on organ blood flows and systemic hemodynamics. Male Fischer 344 rats (n = 24)
      were randomized to a group that received a 12.5% (wt/wt) Gln-enriched enteral
      diet or an isonitrogenous isocaloric control diet for 14 days. Blood flow
      measurements were performed at day 16 using 46Sc-labeled microspheres. In the Gln
      enriched group, higher organ blood flows were measured in the stomach (51%), the
      pancreas (35%), small intestine (32%), and colon (55%), compared with controls.
      No differences were found in systemic hemodynamic parameters between the control
      and Gln-supplemented groups. A possible role for nitric oxide in this splanchnic
      vasodilation was investigated. Daily urinary nitrate excretion was measured
      during the study but showed no significant differences between the control and
      Gln-fed animals. No differences were found in plasma levels of the vasodilating
      hormone glucagon between the groups. These results show that a Gln-enriched
      enteral diet increased splanchnic blood flow, which was not mediated by
      pancreatic glucagon or increased nitric oxide production as determined by urinary
      nitrate excretion.

PMID- 7810651
TI  - Central vagal activation by TRH induces gastric hyperemia: role of CGRP in
      capsaicin-sensitive afferents in rats.
AB  - The role of calcitonin gene-related peptide (CGRP) in the vagal cholinergic
      mediated increase in gastric mucosal blood flow (GMBF) induced by the stable
      thyrotropin-releasing hormone (TRH) analogue RX-77368 injected intracisternally
      (ic, 30 ng) was investigated in urethan-anesthetized rats using the hydrogen gas
      clearance technique. alpha-CGRP (14 micrograms.kg-1.h-1) or bethanechol (150
      micrograms.kg-1.h-1) infused close intra-arterially to the stomach or RX-77368
      injected intracisternally increased GMBF by 76, 102, and 131%, respectively, 30
      min after administration. The CGRP antagonist, human CGRP-(8-37) [hCGRP-(8-37)],
      injected intravenously (15 micrograms/kg bolus and 3 micrograms.kg-1.h-1)
      inhibited by 100, 97, and 73% the gastric hyperemic response to alpha-CGRP, TRH
      analogue, and bethanechol, respectively, whereas the substance P antagonist CP
      96,345 (3 mg/kg iv) had no effect. In capsaicin-pretreated rats, hCGRP-(8-37) no
      longer blocked the increase in GMBF induced by intracisternal RX-77368. These
      results suggest that the gastric hyperemic response to central vagal activation
      induced by intracisternal TRH analogue at 30 ng is mediated by local effector
      function of capsaicin-sensitive afferent fibers releasing CGRP.

PMID- 7810652
TI  - Validation studies of Bilitec 2000: an ambulatory duodenogastric reflux
      monitoring system.
AB  - Bilitec 2000, a fiber-optic spectrophotometer, detects duodenogastric (DG) reflux
      in an ambulatory setting independent of pH by measuring bilirubin in bile.
      Studies were performed for independent validation and better understanding of
      limitations of this system. Bilitec and a conventional spectrophotometer were
      used to assess the effect of gastric acidity on the spectral absorbance of
      refluxed DG contents, employing bilirubin ditaurate (BDT) and human bile. Total
      bile acid concentrations correlated with Bilitec absorption. BDT and bile had
      hypsochromic shift (400 nm) in spectrophotometric maximum wavelength (lambda max;
      450 nm) in an acidic environment (pH < 3.5), corresponding to an approximately
      30% decrease in absorption measured by Bilitec. Bile acid concentrations
      correlated strongly with Bilitec absorption for all 63 samples (R = 0.82) with pH
      > 3.5 (n = 31, R = 0.81), but correlation was less strong for 32 samples with pH
      < 3.5 (R = 0.70). As currently designed, Bilitec adequately measures DG reflux
      but underestimates it by at least 30% in acidic medium (pH < 3.5). Design
      modifications are suggested for improving the sensitivity of this equipment.

PMID- 7810653
TI  - Epidermal growth factor attenuates jejunal mucosal injury induced by oleic acid:
      role of mucus.
AB  - Epidermal growth factor (EGF) is present in biliary, pancreatic, and Brunner's
      gland secretions. The aim of the present study was to assess the effects of EGF
      on lipid-induced mucosal injury. The proximal jejunum of anesthetized rats was
      cannulated for perfusion of the lumen with emulsified oleic acid (40 mM oleic
      acid in 20 mM sodium taurocholate; pH 6.0). Mucosal epithelial integrity was
      monitored by measuring the blood-to-lumen clearance of 51Cr-labeled EDTA.
      Perfusion of the lumen with emulsified lipid increased EDTA clearance. Addition
      of EGF (0.5 ng/ml) to the lipid emulsion ameliorated the lipid-induced increase
      in EDTA clearance. Perfusion of the lumen with EGF alone stimulated mucus
      secretion from goblet cells. This effect of EGF was abolished by atropine. In
      addition, in atropinized animals there was 1) an exaggeration of the lipid
      induced injury and 2) a loss of the protective effect of EGF. Our findings
      provide evidence supporting the hypothesis that EGF provides protection against
      lipid-induced mucosal injury, in part, by stimulating mucus production.

PMID- 7810654
TI  - In vitro and in vivo regulation of hepatic mitogen-activated protein kinases in
      fetal rats.
AB  - We have studied the role of mitogen-activated protein (MAP) kinases in fetal
      hepatocyte growth in vitro and in vivo. With myelin basic protein (MBP) as the
      phosphate acceptor, kinase activity in cultured fetal hepatocyte lysates
      increased fourfold after exposure to transforming growth factor-alpha (TGF-alpha)
      for 10 min. This TGF-alpha-responsive MBP kinase activity was accounted for by
      five distinct MAP kinase isoforms detected by Western immunoblotting. All had
      negligible activity in cultured fetal hepatocytes under basal conditions.
      Treatment of fetal hepatocytes with hepatocyte growth factor led to activation of
      the predominant isoforms, relative molecular weight (M(r)) = 42,000 and 44,000 in
      a manner indistinguishable from TGF-alpha, whereas insulin had no effect. All
      five of the immunoreactive MAP kinases were present in both fetal and adult liver
      homogenates. The M(r) = 42,000 and 44,000 isoforms were only minimally activated
      in vivo. We conclude that the mitogen-independent growth exhibited by fetal
      hepatocytes in primary culture is not associated with tonic activation of the MAP
      kinase system. Our data support the possibility that fetal hepatic growth may be,
      in part, independent of the action of growth factors as mediated via the MAP
      kinase system.

PMID- 7810655
TI  - Neuroimmune communication in the submucous plexus of guinea pig colon after
      sensitization to milk antigen.
AB  - We investigated electrical and synaptic behavior of neurons in the colonic
      submucous plexus during exposure to beta-lactoglobulin in guinea pigs sensitized
      by ingestion of milk. Microelectrodes were used to record electrical and synaptic
      behavior in neurons from milk-sensitized and nonsensitized age-matched animals
      during exposure to beta-lactoglobulin. Neurons in sensitized animals were
      hyperexcitable. Application of the histamine H2 antagonist cimetidine reversed
      the hyperexcitability, suggesting endogenously released histamine as one of the
      responsible factors. Antigenic exposure suppressed stimulus-evoked nicotinic
      cholinergic fast excitatory postsynaptic potentials (EPSPs). This was blocked by
      the selective histamine H3 antagonist burimamide. Suppression of the EPSPs
      resulted from presynaptic inhibition of acetylcholine release. Increased neuronal
      excitability and suppression of synaptic transmission was only found in milk
      sensitized intestine, not in the intestine from age-matched nonsensitized
      animals. We concluded that signaling from mucosal mast cells to the enteric
      nervous system is important in colonic defense against antigenic threats.
      Histamine is a paracrine messenger in the communication network.

PMID- 7810656
TI  - Interleukin-6 inhibits hepatocyte taurocholate uptake and sodium-potassium
      adenosinetriphosphatase activity.
AB  - The potential effects of cytokines on hepatocellular transport functions remain
      undefined. Interleukin-6 (IL-6) is a cytokine that is produced in sepsis,
      hepatitis, and other inflammatory conditions often associated with cholestasis.
      Using cultured rat hepatocytes, we have investigated the effects of IL-6 on
      hepatocellular bile salt uptake. Because hepatocyte Na(+)-K(+)
      adenosinetriphosphatase (ATPase) produces the electrochemical gradient that
      drives sodium-dependent bile salt contransport, we also examined the effects of
      IL-6 on Na(+)-K(+)-ATPase activity. Hepatocytes cultured for 20 h in media
      containing IL-6 exhibited a dose-dependent noncompetitive inhibition of
      [3H]taurocholate uptake, which was maximal at an IL-6 dose of 100 U/ml. IL-6
      treatment had no effect on hepatocyte sodium-independent taurocholate uptake.
      Northern blotting of RNA from cultured hepatocytes revealed that IL-6 had no
      effect on steady-state RNA levels of the Na(+)-taurocholate transporter (Ntcp).
      Hepatocytes incubated with IL-6 for 20 h, however, exhibited a 55% decrease in
      hepatocyte Na(+)-K(+)-ATPase activity. This effect also was dose dependent, with
      maximal inhibition occurring at an IL-6 dose of 100 U/ml. Similar treatment with
      IL-6 did not influence hepatocyte Mg(2+)-ATPase activity. The inhibition of Na(+)
      K(+)-ATPase activity induced by IL-6 provides a putative mechanism for the
      observed inhibition of sodium-dependent taurocholate uptake. Since modulation of
      bile salt transport and Na(+)-K(+)-ATPase activity occurred at IL-6
      concentrations comparable to the serum levels observed in patients with severe
      inflammatory states, these findings have potential pathophysiological relevance
      for the cholestasis of sepsis and other inflammatory disorders.

PMID- 7810657
TI  - Caco-2 cells express type I interleukin-1 receptors: ligand binding enhances
      proliferation.
AB  - We examined the effect of interleukin-1 (IL-1) on the rate of proliferation of
      the human colon carcinoma Caco-2 and characterized the human intestinal
      epithelial cell IL-1 receptor (IL-1R). IL-1 dose dependently increased tritiated
      thymidine uptake in confluent Caco-2 monolayers fed complete growth medium. An
      anti-IL-1 beta completely blocked the increase in tritiated thymidine uptake,
      whereas an IL-1 receptor antagonist human recombinant blocked it partially. In
      long-term culture, IL-1 increased DNA content over control, an effect similar to
      that of epidermal growth factor (EGF). Unlike EGF, IL-1 did not enhance tritiated
      thymidine uptake in Caco-2 monolayers grown in serum-free medium, implying that
      IL-1 needs a cofactor(s) to elicit its proliferative effect. Cross-linking 125I
      IL-1 beta to Caco-2 membranes revealed a binding protein of approximately 80 kDa
      with binding saturated at approximately 2.5 x 10(9) M-1 consistent with that for
      the type I IL-1R. cDNA transcribed from Caco-2 mRNA and amplified by polymerase
      chain reaction, using complementary oligonucleotides, resulted in a reaction
      product matching the sequence of the type I IL-1R. Our results demonstrate that
      IL-1 enhances proliferation of Caco-2 cells. This effect requires the presence of
      an unidentified cofactor(s). Also, Caco-2 cells express the type I IL-1R.

PMID- 7810658
TI  - Regional differences in glycoconjugates of intestinal M cells in mice: potential
      targets for mucosal vaccines.
AB  - We have used a panel of lectins and antibodies to describe the composition of
      complex carbohydrates associated with M cells in various regions of the
      intestinal tract of adult BALB/c mice. The fucose-specific lectin Ulex europaeus
      agglutinin type I (UEA I) is a marker of M cells in the small intestine and
      recognized M cells at an early stage of differentiation. Subpopulations of M
      cells in a single follicle-associated epithelium (FAE) could be distinguished by
      different fucose-specific probes. Certain lectins revealed that M cells have
      basal processes that extend into the underlying lymphoid tissue. Colonic and
      rectal M cells display glycosylation patterns distinct from M cells of Peyer's
      patches and are characterized by terminal galactose. UEA I selectively adhered to
      Peyer's patch M cells in mucosal explants and in ligated intestinal loops in
      vivo. The lectin was taken up into endocytic vesicles and transported to the
      intra-epithelial pocket and other domains of the basolateral membrane. Thus M
      cell-specific glycoconjugates could serve as "receptors" for targeting of lectin
      antigen conjugates to the mucosal immune system.

PMID- 7810659
TI  - Hepatic ischemia/reperfusion injury: importance of oxidant/tumor necrosis factor
      interactions.
AB  - Previous studies have demonstrated a role for both tumor necrosis factor (TNF)
      and reactive oxygen intermediates (ROI) in hepatic ischemia/reperfusion (I/R)
      injury. Biologically active TNF was present in liver homogenates in ischemic and
      nonischemic lobes after 2 h of ischemia but without reperfusion. Using an in situ
      liver perfusion model, we measured ROI, TNF, and hepatic enzymes in the effluent
      after 2 h of ischemia. Increased reduction of ferricytochrome C was observed in
      the hepatic effluent, indicative of the formation of ROI. Treatment of animals
      with TNF neutralizing antisera significantly reduced both ROI and aspartate
      aminotransferase (AST). Animals treated with superoxide dismutase (SOD), or SOD +
      catalase (CAT) had greater TNF in the hepatic effluent compared with I/R alone;
      however, SOD or SOD + CAT did not cause additional release of AST.SOD + CAT plus
      anti-TNF serum resulted in significant protection compared with SOD + CAT plus
      control serum. Reperfusion of ischemic liver with 4 mM H2O2 increased both TNF
      and AST. Optimal protection of hepatocellular injury from reperfusion injury is
      achieved with a combination of antioxidants and inhibition of TNF.

PMID- 7810660
TI  - Brush-border disaccharidase synthesis in infant pigs measured in vivo with
      [2H3]leucine.
AB  - Conscious unrestrained piglets were fasted overnight and infused intravenously
      with [2H3]leucine for 6 h. Sucrase isomaltase and lactase phlorizin hydrolase
      were immunoprecipitated from jejunal mucosal membranes, and the
      immunoprecipitates were electrophoresed on polyacrylamide gels. Bands
      corresponding to the pro and mature isoforms of both enzymes were acid
      hydrolyzed. [2H3]leucine isotopic enrichment was measured by gas chromatography
      mass spectrometry using negative chemical ionization. Plasma leucine reached
      isotopic steady state within 90 min. The isotopic enrichment of mucosal leucine
      was 73% of that of plasma leucine. The high mannose and complex glycosylated
      forms of prolactase were in isotopic equilibrium, and their isotopic enrichment
      was 94% of mucosal leucine. The fractional synthesis rates of total and membrane
      protein were 0.45 and 0.65 days-1, whereas the processing rates of mature
      lactase, sucrase, and isomaltase were 0.90, 0.23, and 0.21 days-1, respectively.
      Approximately 65% of the label in the sucrase isomaltase immunoprecipitate was in
      the complex glycosylated precursor, whereas 73% of the label in lactase phlorizin
      hydrolase was in the mature (160 kDa) form. We conclude that the low rate of
      brush-border sucrase synthesis reflects a slow rate at which the complex
      glycosylated precursor is processed to the brush-border form.

PMID- 7810661
TI  - Small intestinal capsaicin-sensitive afferents mediate feedback inhibition of
      gastric emptying in rats.
AB  - Functional studies have implied the existence of small intestinal receptive
      mechanisms for components of chyme to mediate feedback inhibition of gastric
      function. However, it is not known if the sensors are in the wall of the small
      intestine or located at another site. The present studies evaluated the
      localization of receptive mechanisms mediating intestinal feedback inhibition of
      gastric emptying by functional ablation of intestinal capsaicin-sensitive
      afferents. Perfusion of the small intestine of conscious rats with hydrochloric
      acid (0.1 N; total amount 50 meq), glucose (1 M; total amount 90 mg), or a lipid
      emulsion (Intralipid 10%; total amount 50 mg) inhibited gastric emptying. One to
      7 days after perfusion of the intestine with capsaicin (3.6 mumol), feedback
      inhibition of gastric emptying produced by acid, glucose, or lipid was inhibited
      100, 59, and 42%, respectively. We conclude that acid-induced inhibition of
      gastric emptying is mediated entirely by small intestinal capsaicin-sensitive
      afferent neurons and that a major portion of the glucose-induced inhibition of
      gastric emptying is mediated by small intestinal afferents. However, only a minor
      part of the response to lipid is mediated by this pathway.

PMID- 7810662
TI  - Actions of cholecystokinin and norepinephrine on vagal inputs to ganglion cells
      in guinea pig gallbladder.
AB  - Previous studies have demonstrated that all guinea pig gallbladder neurons
      receive nicotinic synaptic input and that cholecystokinin (CCK) and
      norepinephrine have presynaptic facilitory and inhibitory effects, respectively,
      on these fast synaptic events. The current study was undertaken to determine the
      sources of the cholinergic terminals that provide nicotinic input to gallbladder
      neurons. To stimulate potential extrinsic inputs to gallbladder neurons, a
      stimulating electrode was placed on the nerve bundles that pass along the cystic
      duct. Stimulation of these nerves elicited fast excitatory postsynaptic
      potentials (EPSPs) in gallbladder neurons that were sensitive to hexamethonium,
      facilitated by CCK, and inhibited by norepinephrine. After vagotomy, most neurons
      (14 of 18) did not exhibit any nicotinic input. However, some neurons (3 of 18)
      did exhibit fast EPSPs in response to fiber tract stimulation, but not cystic
      nerve stimulation, indicating that interganglionic communication does exist
      amongst gallbladder neurons. These results demonstrate that the vagus nerves
      provide the major nicotinic input to gallbladder neurons. Furthermore, these data
      suggest that vagal terminals within gallbladder are a site of neurohormonal
      modulation of gallbladder ganglionic output by CCK, norepinephrine, and possibly
      other compounds.

PMID- 7810663
TI  - Induction of postprandial intestinal motility and release of cholecystokinin by
      polyamines in rats.
AB  - Polyamines are known to play a major role in postprandial adaptation of the
      digestive tract. Experiments were designed to determine whether ingested
      polyamines induce change in intestinal motility associated with a cholecystokinin
      (CCK) release and whether endogenous polyamines are involved in the intestinal
      and colonic motor response to a meal. Intestinal and colonic motility was
      assessed in rats equipped with intestinal electrodes, and plasma CCK was
      determined using a bioassay. Orogastric administration of putrescine, spermidine,
      or spermine (20 mumol) disrupted intestinal migrating myoelectric complexes
      (MMCs) and increased the frequency of colonic spike bursts. After a 6-day
      treatment with the ornithine decarboxylase inhibitor alpha
      difluoromethylornithine, the duration of postprandial disruption of MMCs, but not
      the stimulation of colonic motility, induced by a 3-g meal was significantly
      reduced. The duration of MMC disruption and the increase in colonic spike burst
      frequency after spermidine administration (20 mumol) were significantly reduced
      by CCK-A and CCK-B antagonists. Eight minutes after saline administration plasma
      CCK concentration was 0.9 +/- 0.4 pM; it rose to 4.7 +/- 2.8 pM, 8 min after
      spermidine (20 mumol). These results indicate that exogenous polyamines disrupt
      intestinal MMCs and stimulate colonic motility through a release of CCK acting at
      CCK-A and CCK-B receptors and suggest that endogenous polyamines are involved in
      the postprandial control of intestinal motility.

PMID- 7810664
TI  - Interleukin-1 beta inhibits gastric histamine secretion and synthesis in the rat.
AB  - Interleukin-1 beta (IL-1 beta) is the most potent inhibitor of gastric acid
      secretion known at present. Although histamine has been shown to be an important
      mediator of gastric acid secretion, the effect of IL-1 beta on gastric histamine
      mobilization has not been studied. In the present study, the effects of IL-1 beta
      on gastric acid secretion and gastric histamine mobilization were investigated in
      conscious rats with both gastric and vesical fistulas. IL-1 beta (5 micrograms/kg
      iv) significantly inhibited basal acid secretion but did not affect basal urinary
      histamine excretion and fundic histidine decarboxylase (HDC) activity. Gastrin-17
      I (1 nmol.kg-1.h-1) caused a marked increase in acid secretion, urinary histamine
      secretion, and fundic HDC activity. IL-1 beta (5 micrograms/kg iv) completely
      inhibited gastrin-induced acid secretion and partially inhibited urinary
      histamine excretion and fundic HDC activity. Pretreatment with indomethacin (10
      mg/kg ip) partially reversed the inhibitory effects of IL-1 beta on gastrin
      stimulated fundic HDC activity and acid secretion. These findings indicate that
      IL-1 beta inhibits gastric histamine mobilization through both prostaglandin
      dependent and prostaglandin-independent pathways. Furthermore, it is suggested
      that the inhibitory action of IL-1 beta on gastric acid secretion is mediated by
      the inhibition of gastric histamine mobilization.

PMID- 7810665
TI  - Characterization and quantification of a pharyngo-UES contractile reflex in cats.
AB  - We characterized and quantified a reflex from the pharyngeal mucosa to the upper
      esophageal sphincter (UES). Seventeen cats were decerebrated, and the pharynx was
      exposed by opening the cricothyroid ligament. UES motor activity was assessed by
      recording electromyographic (EMG) activity from the pharyngeal constrictors,
      i.e., the thyropharyngeus (TP) and cricopharyngeus (CP). The pharyngeal mucosa
      was stimulated by touch or pressure. Both stimuli activated contraction of the CP
      primarily when applied to the naso-, laryngo-, or hypopharynx, but pressure was
      more effective. The anteromedial portion of the hypopharynx was the most
      sensitive zone, but there was no strong stimulus-response relationship. The
      reflex response to a 1-s stimulus occurred at a delay of 0.46 +/- 0.06 s and
      lasted 4.5 +/- 0.5 s. This pharyngo-UES reflex was blocked by anesthesia of the
      mucosa or transection of the glossopharyngeal or pharyngoesophageal nerves but
      not the vagus nerves. In contrast, the esophago-UES contractile reflex was not
      blocked by anesthesia of the pharyngeal mucosa or transection of the
      glossopharyngeal nerves but was blocked by transection of either the vagus or
      pharyngoesophageal nerves. We concluded that the pharyngo-UES contractile reflex
      was activated by pharyngeal mucosal mechanoreceptors whose afferent limb was the
      glossopharyngeal nerve and whose efferent limb was the pharyngoesophageal branch
      of the vagus nerve.

PMID- 7810666
TI  - Effects of continued NO inhibition on portal hypertensive syndrome after portal
      vein stenosis in rat.
AB  - The present study investigated whether chronic nitric oxide (NO) inhibition
      prevents the hyperdynamic circulatory syndrome that appears in rats after partial
      portal vein ligation (PPVL). N omega-nitro-L-arginine methyl ester (L-NAME; 30
      micrograms.kg-1.min-1, n = 17), a NO biosynthesis inhibitor, or vehicle (n = 17)
      was infused continuously from PPVL through subcutaneously osmotic pumps. Studies
      were performed, in ketamine-anesthetized Sprague-Dawley rats, in one-half of the
      animals at 4 days and in the remaining one-half at 8 days from PPVL. At 4 days,
      PPVL rats treated with L-NAME had higher mean arterial pressure (MAP), systemic
      vascular resistance (SVR), and splanchnic arteriolar resistance (SAR) and lower
      cardiac output and portal venous inflow (PVI) than PPVL rats treated with vehicle
      (P < 0.05). Similarly, at 8 days PPVL rats treated with L-NAME had higher MAP and
      SVR and lower cardiac output (P < 0.05) than PPVL rats treated with vehicle. In
      contrast, PVI and SAR were similar. At 4 days plasma volume and mesenteric
      systemic shunting were lower, although nonsignificantly, in PPVL rats treated
      with L-NAME. This trend completely disappeared at 8 days. L-NAME did not change
      portal pressure at either 4 or 8 days. After 4 days of continuous treatment with
      L-NAME, nonportal hypertensive control rats had a significantly higher MAP, lower
      cardiac index and PVI, and higher SVR and SAR than nonportal hypertensive rats
      treated with vehicle. Contrary to PPVL rats, these effects were maintained after
      8 days of treatment. The present study shows that NO contributes to the systemic
      disturbances of portal hypertension. However, NO inhibition delayed but did not
      prevent the splanchnic vasodilation that appears after PPVL, suggesting that
      other factors could also be involved.

PMID- 7810667
TI  - IL-8 secretion and neutrophil activation by HT-29 colonic epithelial cells.
AB  - This study examines the ability of HT-29 human colonic epithelial cells to
      stimulate neutrophil migration and adhesion. Interleukin-8 (IL-8), a potent
      neutrophil chemoattractant, was detected in conditioned media from both
      unstimulated (1.1 ng/ml) and IL-1 beta-stimulated (16.1 ng/ml) HT-29 cultures.
      Conditioned medium from IL-1 beta-exposed HT-29 cells stimulated neutrophil
      migration (395% of control, P < 0.01), and this effect was completely inhibited
      by anti-IL-8 antibody. HT-29 medium also induced shedding of neutrophil L
      selectin and increased expression of neutrophil CD11/CD18 adhesion receptors.
      Coculture of HT-29 cells with human endothelial cell monolayers resulted in
      increased neutrophil transendothelial migration (169% of control, P < 0.01),
      which was blocked by both anti-IL-8 and anti-CD18 antibody. Northern
      hybridization analysis demonstrated increased levels of mRNA for IL-8 and
      intercellular adhesion molecule-1 (ICAM-1) in cytokine-treated HT-29 cells.
      Cytokine stimulation of HT-29 monolayers was also associated with increased
      neutrophil adhesion to these cells. Neutrophil-HT-29 cell adhesion was blocked by
      monoclonal antibodies to neutrophil CD18 or to ICAM-1 on the HT-29 cells (86% and
      56% inhibition, respectively, P < 0.01 for both). These data suggest that IL-8
      secretion by activated colonic epithelial cells may contribute to neutrophil
      extravasation and tissue infiltration in intestinal inflammation.

PMID- 7810668
TI  - PGE generates intracellular cAMP and accelerates mucin secretion by cultured dog
      gallbladder epithelial cells.
AB  - Mucin is the main secretory product of gallbladder epithelial cells. Increased
      gallbladder mucus secretion has been implicated in gallstone formation in humans.
      The mechanisms underlying control of mucin synthesis and secretion by the
      gallbladder are not known. This study aimed to elucidate the efficacy of a panel
      of secretagogues to stimulate mucin secretion and to determine the intracellular
      second messengers involved. Studies were carried out on normal well
      differentiated epithelial cells from dog gallbladder grown in monolayer culture.
      Intracellular adenosine 3',5'-cyclic monophosphate (cAMP) as measured by
      radioimmunoassay increased in response to prostaglandin (PG) E2, PGE1, vasoactive
      intestinal peptide, epinephrine, and isoproterenol. The greatest effect, a 37
      fold increase in cAMP level, was noted with PGE2 at 1.0 microM concentration. In
      contrast, three breakdown products of phosphatidylinositol (inositol
      triphosphate, inositol bisphosphate and inositol monophosphate) were not detected
      with any of the secretagogues tested. Assay of mucin secretion using tritiated N
      acetyl-D-glucosamine, a mucin precursor, showed that the same secretagogues noted
      to increase intracellular cAMP led to an increase in mucin secretion. No
      correlation was noted, however, between the magnitude of the intracellular cAMP
      rise and the amount of mucin secreted. A membrane-permeable form of cAMP,
      dibutyryl cAMP, mimicked PGE2-induced mucin secretion. The results unequivocally
      show that secretagogue-stimulated mucin secretion in these normal gallbladder
      epithelial cells can proceed via a cAMP signal transduction pathway.

PMID- 7810670
TI  - Oxidant stress decreases Na+/H+ antiport activity in bovine pulmonary artery
      endothelial cells.
AB  - We determined the effects of oxidant stress by the use of tert-butyl
      hydroperoxide (t-BOOH) on Na+/H+ exchange in pulmonary artery endothelial cells.
      Monolayers were exposed to the hydroperoxide, followed by measurement of
      intracellular pH and the rate of recovery from acidosis by utilizing the pH
      sensitive probe 2',7'-bis(carboxyethyl)-5(6)- carboxyfluorescein. t-BOOH (0.4 mM)
      decreased the rate of acid recovery after a 2-h exposure without evidence of
      overt cytotoxicity (51Cr-release assay). Glutathione repletion (N-acetyl-L
      cysteine) abolished the effect of the hydroperoxide. Lowering intracellular
      glutathione with buthionine sulfoximine decreased the acid recovery rate at a
      dose of t-BOOH (0.04 mM) that was not normally associated with a change in this
      parameter. Preincubation with vitamin E had no protective effect. Dithiothreitol
      abolished the effect of the hydroperoxide, suggesting oxidation of protein
      sulfhydryl groups as a mechanism for the altered kinetics of acid recovery. There
      was no difference in cell buffering capacity between control and treated
      monolayers. The findings suggest that the decrease in Na+/H+ antiport activity in
      this model of oxidant stress represents an early perturbation of membrane
      function and illustrate the role of the glutathione redox system in maintaining
      the functional integrity of the Na+/H+ antiport in these cells.

PMID- 7810669
TI  - Regulation of CTP:choline-phosphate cytidylyltransferase by polyunsaturated n-3
      fatty acids.
AB  - Disaturated phosphatidylcholine (DSPC) is the most distinctive surface-active
      lipid in pulmonary surfactant. The feeding of docosahexanoic acid (DHA) 22:6 n-3
      has recently been described to elevate the levels of DSPC in rodent lung. The
      purpose of the present study was to determine the mechanisms by which this n-3
      fatty acid might regulate CTP:choline-phosphate cytidylyltransferase, a key
      enzyme required for phosphatidylcholine (PC) synthesis. Cytidylyltransferase
      exists in lung cytosol as a large lipid-associated aggregate (H form) which is
      active, and as an inactive, low-molecular-weight species (L form). Fatty acids in
      vitro stimulate and aggregate the inactive L form to the active H form. Short
      term (2-h) and long-term (24-h) exposure of fetal lung explants to DHA (150
      microM) stimulated choline incorporation into PC by 54 and 64%, respectively. The
      fatty acid also enhanced DSPC synthesis by 88%. These changes were associated
      with an increase in the activity of cytidylyltransferase by 63% after addition of
      DHA to the explant medium. In vitro, DHA (50 microM) stimulated L form nearly 15
      fold and appeared to be a more potent activator and aggregator of the enzyme than
      either linoleic 18:2 n-6 or arachidonic 20:4 n-6 acids. The effect of DHA on L
      form activation was comparable, however, with other members of the n-3 family.
      Kinetic studies revealed that DHA increased the maximum velocity of enzyme
      reaction for cytidylyltransferase, although it did not alter the Michaelis
      constant of the enzyme for CTP. These observations provide in vitro evidence that
      n-3 fatty acids may play an important role in the regulation of surfactant PC
      biosynthesis.

PMID- 7810671
TI  - Surfactant protein A modulates release of reactive oxygen species from alveolar
      macrophages.
AB  - The production and release of reactive oxygen species (the respiratory burst) is
      a common metabolic pathway linked to several macrophage-related reactions. The
      most abundant surfactant protein A (SP-A) binds to alveolar macrophages (AM)
      through a specific surface receptor with high affinity. Because such binding
      might initiate or modulate the respiratory burst, we wanted to know whether and
      how SP-A affects the oxygen radical release from AM. To answer these questions,
      we measured the release of reactive oxygen species from rat AM under various in
      vitro conditions using enhanced chemiluminescence systems. We prepared SP-A from
      pulmonary surfactant isolated either from silica-treated rats or adult dogs.
      Resident AM were harvested from pathogen-free Wistar rats by lung lavage. Adhered
      and nonadhered AM were assessed on protein-free or protein-coated surfaces of 96
      well microtiter plates. On protein-free surfaces, the sole addition of SP-A
      failed to induce measurable oxygen radical release from 2 x 10(5) adhered or
      nonadhered AM, while zymosan opsonized with SP-A induced a marked increase over
      control. On protein-coated surfaces, AM respond differently depending on the
      coated protein: on SP-A-coated surfaces, a dose-dependent enhancement of oxygen
      radical release with a mean effective concentration of approximately 1.15
      micrograms/ml was found. No such enhancement was seen on plates coated with
      similar amounts of either human fibronectin or collagen, and the enhancement with
      serum albumin was not dose related. Our data demonstrate that SP-A only enhances
      oxygen radical release from AM if SP-A is fixed to zymosan or the surface of the
      reaction vial in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7810672
TI  - Perinatal hypocuprosis affects synthesis and composition of neonatal lung
      collagen, elastin, and surfactant.
AB  - To investigate the role of iron, ascorbate, and fructose on copper depletion and
      the effect of copper depletion on neonatal lung collagen, elastin, and
      surfactant, female rabbits were fed a control diet [10 parts per million (ppm)
      copper], a basal marginal copper diet (1.5 ppm), or a basal diet containing a
      high concentration of iron (1,750 ppm), ascorbic acid (1%, wt/wt), or fructose
      (20% of carbohydrates, wt/wt) or a combination of iron, ascorbic acid, and
      fructose throughout gestation. Whereas 10% of neonates in the control group died
      in the first 24 h, 27-67% of the offspring of rabbits fed the marginal copper
      diet died. Birth weight was also lower for the pups of the females fed the
      marginal copper diets. Lungs of neonates born to females fed iron or ascorbate
      and marginal copper diets had low levels of copper, high proportions of acid
      extractable, high-molecular-weight collagen, and low lysyl-oxidase activities,
      consistent with incomplete maturation of collagen. The bronchoalveolar lavage
      fluids of newborns whose mothers were fed marginal copper diets alone or in
      combination with iron and/or ascorbate had lower levels of total surfactant
      phospholipids than the fluids from lungs of control newborns. The lower
      surfactant phospholipid content of these groups could be attributed mainly to
      lower phosphatidylcholine and, in particular, dipalmitoylphosphatidylcholine
      levels. These results suggest that high maternal intakes of iron, ascorbate, or
      their combination in pregnancy deplete biologically available copper, which in
      turn induces neonatal lung abnormalities.

PMID- 7810673
TI  - Lung injury after silica instillation is associated with an accumulation of iron
      in rats.
AB  - It has been postulated that the incomplete complexation of host iron by the
      surface of mineral oxides is essential in in vivo lung injury after exposure to
      these dusts. We investigated the associations between in vivo iron accumulation
      after intratracheal instillation of silica dust in rats and 1) concentrations of
      antioxidants and oxidized products in the lung and 2) an index of chronic
      fibrotic injury. Fifty milligrams of minusil were intratracheally instilled into
      60-day-old, male Sprague-Dawley rats. Ionizable Fe3+ complexed to the surface of
      silica increased from 12.7 +/- 1.4 mumol/g to values as high as 42.5 +/- 9.1
      mumol/g dust after instillation. Corresponding to this elevation of surface
      adsorbed metal, concentrations of iron in bronchoalveolar lavage fluid, lung
      tissue, plasma, and liver tissue all increased. Antioxidant molecules in lung
      tissue, including ascorbate, urate, and glutathione, all decreased, whereas
      superoxide dismutase increased. Oxidized products in the lung tissue, measured as
      thiobarbituric acid-reactive products, similarly increased, reflecting an oxidant
      stress. Dietary depletion of iron stores before instillation of silica dust
      resulted in low iron stores (hematocrit values of 21.8 +/- 1.9) and low iron
      concentrations in lavage fluid, lung tissue, and liver tissue. Rats on iron
      depleted diets demonstrated a diminished fibrotic injury after dust instillation.
      Complexation of iron by the dust surface may be central in collagen deposition
      after silica exposure.

PMID- 7810674
TI  - Effects of TGF-beta and TNF-alpha on procoagulant and fibrinolytic pathways of
      human tracheal epithelial cells.
AB  - The epithelial lining of the airways is subject to injury through several
      processes, including infections, bronchiolitis, and fume exposures. Because
      airway fibrin deposition influences the course of local injury, we examined how
      two inflammatory cytokines influenced fibrin formation and clearance in human
      tracheal epithelial cells (TEC). TEC were treated with transforming growth factor
      beta (TGF-beta) and tumor necrosis factor-alpha (TNF-alpha). TNF-alpha increased
      release of tissue factor (TF)-related procoagulant activity that, through
      generation of factor Xa, promotes assembly of the prothrombinase complex at the
      cell surface. Fibrinolytic activity was plasminogen dependent and due to both
      urokinase (uPA) and tissue plasminogen activator (tPA). The cells expressed
      plasminogen activator inhibitor 1 (PAI-1), but relatively little PAI-2.
      Depression of fibrinolysis by TGF-beta correlated with increased PAI-1.
      Conversely, TNF-alpha increased plasminogen activator (PA) activity due to
      increased uPA. Fibrinolytic activity was inhibited by actinomycin D and
      cyclohexamide, but changes in mRNAs for uPA, tPA, PAI-1, and TF by either
      cytokine were not appreciable. PAI-2 mRNA was not found. The data indicate that
      TGF-beta decreases the fibrinolytic capacity of TEC, suggesting that this
      cytokine promotes fibrin retention. TNF-alpha increases expression of both
      procoagulant and fibrinolytic activities; this differential regulation could
      favor both pericellular fibrin formation and dissolution.

PMID- 7810675
TI  - Surfactant protein A stimulation of inflammatory cytokine and immunoglobulin
      production.
AB  - Pulmonary surfactant plays a variety of roles related to the regulation of immune
      function in the lung. Of particular interest in this regard is surfactant protein
      A (SP-A), a calcium-dependent lectin. We have reported previously that SP-A
      enhances concanavalin A-induced proliferation, and in this study we examined the
      secretion of tumor necrosis factor-alpha (TNF-alpha), interleukins 1 alpha, 1
      beta, and 6, and interferon-gamma by human peripheral blood mononuclear cells.
      Levels of all of the cytokines except interferon-gamma were increased by SP-A. In
      rat peripheral blood cells, splenocytes, and alveolar macrophages we found a
      similar enhancement of TNF-alpha release by SP-A. In combinations of SP-A and
      surfactant lipids, the increased levels of TNF-alpha resulting from SP-A
      treatment decreased as the lipids increased. At higher relative concentrations of
      SP-A, the lipids had little or no effect. SP-A also enhanced the production of
      immunoglobulins A, G, and M by rat splenocytes. Levels of each isotype were
      increased severalfold over control levels. These data demonstrate that SP-A is
      capable of modulating immune cell function in the lung by regulating cytokine
      production and immunoglobulin secretion.

PMID- 7810676
TI  - Oxygen-induced changes in protein synthesis and cell proliferation in cultured
      lung slices.
AB  - Elevated fractions of inspired O2 induce significant remodeling of the airways
      and vasculature of the lung. The present study was undertaken to determine the
      direct effects of altered levels of O2 on protein synthesis and cell
      proliferation in lung tissue cultured in vitro. Rat lungs were inflated with low
      melt agarose, cut transversely into 1-mm sections, and cultured in a serum-free
      medium for up to 7 days in the presence of 10, 21, 40, or 70% O2. Tissue
      structure integrity was maintained as assessed by light and electron microscopy.
      Fractional synthesis rates (FSR, %protein/day) of soluble protein from cultured
      lung homogenates demonstrated an O2 concentration-dependent response. Tissue
      cultured in the presence of 70% O2 exhibited the highest FSR. The FSR of tissue
      cultured in 21 or 40% O2 did not differ and demonstrated FSR values greater than
      tissue cultured in 10% O2. Cell proliferation was assessed histologically in
      parenchymal gas-exchange regions of lung slices cultured in the presence of 5
      bromo-2'-deoxyuridine. Labeling indexes for tissue cultured in 21, 40, or 70%
      indicated an O2-dependent increase in cell proliferation after 3 days in culture
      followed by a return to baseline levels after 7 days. Tissue cultured in the
      presence of 10% O2 showed no change in cell proliferation over time. The data
      indicate a direct influence of O2 on lung cell growth and proliferation.
      Additionally, these studies show that this in vitro model may be suitable for
      further understanding of the mechanistic basis involved in proliferative events
      during lung injury.

PMID- 7810677
TI  - Transforming growth factor-alpha enhances alveolar epithelial cell repair in a
      new in vitro model.
AB  - Alveolar epithelial type II cells are essential for regenerating an intact
      alveolar barrier after destruction of type I cells in vivo. The first objective
      of these experimental studies was to develop an in vitro model to quantify
      alveolar epithelial cell wound repair. The second objective was to investigate
      mechanisms of alveolar epithelial cell wound healing by studying the effects of
      serum and transforming growth factor-alpha (TGF-alpha) on wound closure. Primary
      cultures of rat alveolar type II cells were prepared by standard methods and
      grown to form confluent monolayers in 48 h. Then a wound was made by denuding an
      area (mean initial area of 2.1 +/- 0.6 mm2) of the monolayer. Re
      epithelialization of the denuded area over time in the presence or absence of
      serum was measured using quantitative measurements from time-lapse video
      microscopy. The half time of wound healing was significantly enhanced in the
      presence of serum compared with serum-free conditions (2.4 +/- 0.2 vs. 17.4 +/-
      0.8 h, P < 0.001). We then tested the hypothesis that TGF-alpha is an important
      growth factor for stimulating wound repair of alveolar epithelial cells.
      Exogenous addition of TGF-alpha in serum-free medium resulted in a significantly
      more rapid wound closure, and, furthermore, the addition of a monoclonal antibody
      to TGF-alpha in the presence of serum significantly decreased fourfold the rate
      of wound closure. Measurement of internuclear cell distance confirmed that both
      cell motility and cell spreading were responsible for closure of the wound. These
      data demonstrate that 1) the mechanisms of alveolar cell repair can be studied in
      vitro and that 2) TGF-alpha is a potent growth factor that enhances in vitro
      alveolar epithelial cell wound closure.

PMID- 7810678
TI  - Maturation of nonadrenergic noncholinergic inhibitory system in normal and
      allergen-sensitized rabbits.
AB  - We investigated the functional existence of the nonadrenergic noncholinergic
      inhibitory (NANCi) system in developing rabbit airways in vitro. Furthermore, we
      evaluated the effect of parenteral exposure to a specific allergen (ragweed) on
      the maturation of this neural pathway. NANCi responses were studied on tracheal
      smooth muscle (TSM) segments obtained from normal and ragweed-sensitized New
      Zealand White rabbits at 1, 2, 4, and 12 wk of age. The TSM segments were removed
      and placed in tissue baths containing modified Krebs-Henseleit solution, atropine
      (1 x 10(-5) M), and propranolol (5 x 10(-6) M). After contraction with neurokinin
      A (1 x 10(-5) M), electrical field stimulation was applied at stimulation
      frequencies ranging from 5 to 30 Hz to determine the frequency that produced
      maximal relaxation. The NANCi response to EFS was measured and expressed as the
      mean (+/- SE) percent relaxation at 20 Hz, because this stimulation frequency
      gave the maximal NANCi response at each age studied. TSM segments obtained from
      control rabbits at 1 wk of age did not demonstrate a NANCi response at the
      frequencies of stimulation used. By contrast, a reproducible NANC relaxation was
      demonstrated in TSM from 2-, 4-, and 12-wk-old rabbits. The magnitude of this
      response was 27 +/- 4.7 (n = 10), 29 +/- 4.8 (n = 9), and 37 +/- 4% (n = 18),
      respectively. The same experiments performed on TSM segments obtained from
      ragweed-sensitized animals gave significantly decreased values of NANCi response.
      In 2-, 4-, and 12-wk-old rabbits, the NANCi responses were 11.5 +/- 3.4 (n = 9),
      11 +/- 2 (n = 13), and 16 +/- 4.2% (n = 14).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7810679
TI  - Characterization of acetylcholinesterase in rabbit intrapulmonary arteries.
AB  - Acetylcholine (ACh) acts on the pulmonary vasculature to evoke vasodilation and,
      in some species, vasoconstriction. The actions of ACh are terminated by its rapid
      hydrolysis by cholinesterases. Aside from histochemical localization studies,
      there is little information on cholinesterase enzymes in pulmonary blood vessels.
      The present study addresses the hypothesis that pulmonary blood vessels contain
      sufficient cholinesterase activity to regulate the action of ACh in these
      tissues. Accordingly, studies were undertaken to characterize and quantify
      cholinesterase activities in pulmonary arteries and veins, quantify inhibition of
      enzyme activity, and investigate functional physiological consequences of
      cholinesterase inhibition. Cholinesterase activities in aorta and trachea also
      were examined for comparison. Kinetic studies showed that the lobar pulmonary
      arterial enzyme has a Michaelis constant of 55.3 +/- 17.0 microM and a maximum
      velocity of 8.6 +/- 2.7 nmol/min/mg protein similar to cholinesterases found in
      other peripheral tissues. Studies with selective inhibitors revealed that > 98%
      of total enzyme activity was attributable to acetylcholinesterase. Similar levels
      of enzyme activity were found in homogenates of lobar branch intrapulmonary
      arteries, intrapulmonary veins, and aorta. The majority of enzyme activity was
      localized to the membrane fraction, although a moderate amount was found in the
      cytosol. Studies in intact intrapulmonary lobar arteries showed that these
      vessels had cholinesterase activity comparable with that found in intact
      trachealis muscle and that neostigmine (10 nM to 10 microM) caused concentration
      dependent inhibition of enzyme activity. In isolated intrapulmonary lobar
      arteries, functional studies showed that 1 and 10 microM neostigmine
      significantly potentiated ACh-induced contractions.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7810680
TI  - Surfactant protein A regulates uptake of pulmonary surfactant by lung type II
      cells on microporous membranes.
AB  - We have investigated the internalization of surfactant by type II cells in
      primary culture. Previously, we demonstrated that type II cells cultured on
      microporous membranes [Transwell membranes (TM)] maintained the morphological
      characteristics of lung pneumocytes and took up surfactant protein and
      phospholipid in a fashion similar to that described for the uptake of surfactant
      by whole lung. In the present study, cells cultured on TM and exposed to
      equivalent amounts of phospholipid (PL) as either natural surfactant or liposomes
      incorporated fivefold greater amounts of natural surfactant PL. The evidence
      supported an important role for surfactant protein A (SP-A), as the incorporation
      of surfactant into type II cells on TM was reduced by anti-SP-A antisera and by
      pretreatment of the surfactant with beta-mercaptoethanol. In addition, the uptake
      of liposomes into type II cells on TM was augmented by SP-A. With the use of
      iodinated bovine SP-A reconstituted in rat surfactant, cells cultured on TM
      showed a 2.6-fold increase in binding and a 3.2-fold stimulation in uptake of SP
      A over that seen with cells cultured on plastic. The change in the slope of the
      total binding curve of 125I-labeled bovine SP-A reconstituted with bovine
      surfactant to type II cells on the two substrates occurred at the same
      concentration of SP-A (17 micrograms/mg), but maximal binding was approximately
      eight times higher for cells on TM than for cells on plastic dishes. Thus, in a
      more physiological environment, i.e., SP-A in surfactant and cells on microporous
      membranes, SP-A plays an important role in the uptake of phospholipids by
      alveolar pneumocytes.

PMID- 7810681
TI  - Immunolocalization of glutathione S-transferase isoenzymes in bronchiolar
      epithelium of rats and mice.
AB  - Ultrastructural immunocytochemistry, using antisera raised against specific
      subunits of glutathione S-transferases, indicated differences in the
      intracellular compartmentalization of these enzymes in the bronchiolar epithelia
      of rats and mice. Antisera raised against subunits of the alpha-class derived
      from both rats (Ya) and mice (Yc) labeled secretory granules in Clara cells of
      rats, but not mice, and they also labeled mitochondria throughout murine
      bronchioles. In contrast, antiserum to a mu-class subunit derived from rats (Yb1)
      did not result in any labeling over the Clara cell granules of rats but produced
      intense labeling over those of mice. Antiserum raised against a rat-derived pi
      class subunit (Yp) did not label Clara cell granules or mitochondria in either
      rats or mice but produced a slight concentration of label over the nuclei of
      murine cells. Variations in the distribution of glutathione S-transferases may
      contribute to interspecies differences in the sensitivity of particular lung
      cells to toxins. Isoenzymes of glutathione S-transferase, secreted into the
      bronchioles of rats and mice, may help to protect the epithelium from
      extracellular toxins.

PMID- 7810682
TI  - A discrete subpopulation of human monocytes expresses a neutrophil-like
      proinflammatory (P) phenotype.
AB  - We have demonstrated that a discrete and naturally occurring subpopulation of
      human monocytes expresses a neutrophil-like proinflammatory (P) phenotype. P
      monocytes constitute 20-30% of the circulating monocyte pool and are
      characterized by 1) avid adherence to extracellular matrix through high-level
      cell-surface expression of alpha 5-, beta 1-, and beta 2-integrins; 2) high
      capacity to produce reactive oxygen species; 3) high content of serine
      proteinases and alpha 1-proteinase inhibitor; and 4) proteolytic activity against
      a soluble peptide human leukocyte elastase substrate, [3H]elastin, and solid
      phase fibronectin, even in the presence of proteinase inhibitors. However, P
      monocytes express little or no cell-surface HLA-DR antigen, suggesting that they
      are unable to participate in specific immune responses. In contrast, the
      remainder of circulating monocytes have a low proinflammatory potential but
      contain the population of monocytes with high-level expression of HLA-DR antigen.
      P monocytes can readily be separated from the remainder of monocytes on the basis
      of 1) their capacity to adhere to fibronectin; and 2) their absent expression of
      HLA-DR antigen when flow cytometry or immunomagnetic beads are used. Our data
      indicate that, when recruited to sites of inflammation, P monocytes can either
      promote resolution of inflammation or contribute to tissue injury.

PMID- 7810684
TI  - Progressive alveolar septal injury in primates exposed to 60% oxygen for 14 days.
AB  - Moderate exposures to hyperoxia are becoming increasingly common in clinical
      medicine as advancing technology allows O2 to be more effectively delivered to
      nonintubated patients. The sensitivity of the lung to injury by a subchronic
      exposure to 60% O2 was investigated, using baboons and serial lobar biopsies.
      Because results obtained from different regions of the lung were compared, the
      alveolar architecture of different lung lobes of three controls was studied, with
      the use of electron microscopic morphometric analyses, to assess possible lobar
      differences in volume, surface, and numerical densities of cells and tissues. In
      animals exposed to 60% O2, the same techniques were used to assess specific
      tissue changes in the epithelial, interstitial, and endothelial compartments of
      the alveolar septa. All six lobes of the normal baboon lung were found to be
      identical with respect to alveolar architecture. Thus, for gases of low
      reactivity and given in high concentrations, such as O2, cross-comparisons
      between different lobes are appropriate. Exposure to 60% O2 was found to cause
      proliferation of alveolar type II epithelium, suggesting a low-grade, chronic
      epithelial injury. Animals allowed to recover for 8 wk in room air showed
      progressive changes in the alveolar interstitium, involving increases in both
      cells and matrix. Because sequential lobar resections were done, animals were
      exposed both to 60% O2 and to the effects of general anesthesia and
      thoracotomies. The exposure to 60% O2 for 2 wk in this experimental setting leads
      to an alveolar septal injury that includes a progressive interstitial fibrotic
      response.

PMID- 7810685
TI  - Sites of superoxide anion production detected by lucigenin in calf pulmonary
      artery smooth muscle.
AB  - Sources of superoxide anion (O2-.) production in calf pulmonary artery smooth
      muscle homogenate and subcellular fractions were examined in this study by
      measurement of the chemiluminescence produced by the reaction of O2-. with 50
      microM lucigenin, because recent evidence suggests that endogenously produced
      reactive O2 species appear to mediate certain vascular responses. In the
      homogenate fraction, an NADH (0.1 mM)-dependent oxidoreductase activity was the
      major detected source of chemiluminescence. NADPH (0.1 mM) produced only 3% of
      the O2-. observed with NADH. Quantitation of certain other potential sources of
      O2-. (under optimized conditions), including xanthine oxidase (0.1 mM
      hypoxanthine), mitochondria (5 mM succinate + 30 microM antimycin),
      cyclooxygenase/lipoxygenase (1 microM arachidonic acid + 0.1 mM NADPH), or
      autooxidation (0.1 mg/ml superoxide dismutase), resulted in the detection of
      minimal amounts (< 3% of NADH) of chemiluminescence. Estimation of mitochondrial
      O2-. production from tissue respiration rates suggests that lucigenin is a poor
      detector of intramitochondrial O2-.. These observations were confirmed by
      examination of chemiluminescence produced by subcellular fractions, where the
      major activity detected was an NADH oxidoreductase, which fractionated in a
      manner closely matching the activity of the microsomal marker enzyme rotenone
      insensitive NADH-cytochrome c reductase. Because this NADH oxidoreductase appears
      to be a major vascular smooth muscle-derived source of O2-. production, this
      system has the potential to be an important endogenous source for the generation
      of vasoactive reactive O2 species.

PMID- 7810683
TI  - Monocytes recruited to sites of inflammation express a distinctive
      proinflammatory (P) phenotype.
AB  - Only a minor proportion of monocytes responds to chemoattractants. To test the
      possibility that chemoattractant-responsive monocytes have distinctive functional
      characteristics, we enriched or depleted monocyte preparations for cells having a
      proinflammatory (P) phenotype and tested their responses to biologically relevant
      chemoattractants. We prepared monocyte subpopulations by one of three independent
      techniques to minimize the chances of artifacts: 1) depletion of P monocytes by
      adherence to fibronectin; 2) enrichment for P monocytes by negative selection for
      HLA-DR antigen; and 3) flow cytometric sorting. We measured responsiveness of
      monocyte subpopulations to N-formyl-Met-Leu-Phe, C5a, zymosan-activated serum,
      and monocyte chemoattractant protein-1 by three parameters: 1) polarization, 2)
      actin polymerization, and 3) directed migration. With each chemoattractant and
      each parameter, there was a striking direct relationship between the
      responsiveness of the monocyte preparations and their content of P monocytes. Our
      data indicate that the capacity of monocytes to be recruited rapidly from the
      vasculature into sites of inflammation is a property of a subpopulation of
      monocytes with a distinctive, neutrophil-like proinflammatory phenotype.

PMID- 7810686
TI  - Properties of a superoxide anion-generating microsomal NADH oxidoreductase, a
      potential pulmonary artery PO2 sensor.
AB  - In this study, we describe properties of a microsomal NADH oxidoreductase that is
      a potential PO2-dependent source of vasoactive reactive O2 species in the calf
      pulmonary artery. Microsomes show an NADH-dependent production of superoxide
      anion (O2-.), as detected by lucigenin-elicited chemiluminescence, a superoxide
      dismutase inhibited reduction of nitro blue tetrazolium (NBT) and 2,6
      dichlorophenol-indophenol, and O2 consumption. The microsomal production of O2-.
      was modulated by physiologically relevant levels of NADH and PO2, and O2-.
      production was reduced by inhibitors of NADH-dependent microsomal electron
      transport. Microsomes catalyzed an NADH-mediated reduction of several electron
      acceptor dyes, cytochrome c (rotenone insensitive) and methemoglobin. On
      reduction with dithionite, a cytochrome with an absorbance at approximately 558
      nm was observed. Arterial O2-. levels (chemiluminescence) were also reduced by
      NBT and microsomal electron transport inhibitors. In pulmonary arteries, NBT
      selectively inhibited PO2 and lactate elicited changes in force generation,
      presumably by trapping O2-. and preventing H2O2 formation. Thus these studies are
      consistent with an involvement of O2-.-derived H2O2 generation via a microsomal
      NADH-cytochrome b558 electron transport system in calf pulmonary artery smooth
      muscle PO2 and lactate-elicited tone responses.

PMID- 7810687
TI  - Ba(2+)-sensitive K+ channels in basal membrane of confluent Madin-Darby canine
      kidney cells.
AB  - A method is described for gaining access to the basolateral membranes of
      confluent Madin-Darby canine kidney (MDCK) cells by surgical reflection of the
      cell layer overlying fluid-filled domes. Single-channel recordings from cell
      attached inside-out and outside-out configurations revealed two K+ channels
      located in the basal membranes of the highly differentiated monolayers. With 140
      mmol/l KCl in pipette, the intermediate-conductance K+ channel displayed outward
      rectification in cell-attached configuration with channel conductances of 65 pS
      for outward part and 17 pS for inward part. In excised-patch recording, this
      channel had a conductance of 92 pS with 140 mmol/l KCl on the extracellular side
      of the patch and 5 mmol/l KCl on the cytosolic side. The maximum conductance
      obtained in symmetrical KCl (140 mmol/l) solution was 140 pS. Ba2+ (1 mmol/l) and
      tetraethylammonium (5 mmol/l) blocked this channel reversibly. Channel open
      probability (Po) was reduced from 0.41 at cytosolic pH 7.4 to 0.14 at pH 6.8 and
      increased to 0.64 at pH 8.0. The channel activity was significantly inhibited by
      elevation of intracellular Ca2+. A small-conductance K+ channel was also observed
      mainly in excised patches with single-channel conductance of 48 pS in symmetrical
      KCl solutions. However, the activity of this channel was partially obscured by
      the intermediate-conductance K+ channel and further analysis was not possible. A
      physiological role of these channels in mediating K+ recycling through the
      monolayer is suggested.

PMID- 7810688
TI  - Acute acidosis inhibits liver amino acid transport: no primary role for the urea
      cycle in acid-base balance.
AB  - To examine further the role of the liver in acid-base homeostasis, we studied
      hepatic amino acid uptake and urea synthesis in rats in vivo during acute
      acidosis and alkalosis, induced by infusion of 1.8 mmol of HCl or NaHCO3 over 3
      h. Amino acids and NH4+ were measured in portal vein, hepatic vein, and aortic
      plasma, and arteriovenous differences of amino acids and urinary urea and NH4+
      excretion were measured. In acidosis, urinary urea excretion was reduced 36% (P <
      0.01), whereas urinary NH4+ excretion increased ninefold (P < 0.01), but the sum
      of urea and NH4+ excretion was unchanged. Total hepatic amino acid uptake, as
      determined from arteriovenous differences, was decreased by 63% (P < 0.01) in
      acidosis, with the major effect being noted with alanine and glycine. Only
      glutamine was released in both acidosis and alkalosis but was not significantly
      different in the two conditions. Since intracellular concentrations of readily
      transportable amino acids were not different at low pH despite accelerated
      protein degradation, these results indicate that hepatic amino acid transport was
      inhibited markedly and sufficiently to explain the observed decrease in urea
      synthesis. Total hepatic vein amino acid content was greater in acidosis than
      alkalosis (P < 0.01). Directly or indirectly, by conversion to glutamine
      elsewhere, these increased amino acids were degraded in kidney and accounted for
      the ninefold increase in urinary NH4+ excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7810689
TI  - Energy transfer assays of rat renal cortical endosomal fusion: evidence for
      superfusion.
AB  - The complex of components necessary to allow endosomal fusion includes both
      membrane-bound receptors and several soluble proteins. Although these factors
      have been isolated from cultured cell lines, and endosomal fusion has been
      reconstituted in vitro for vesicular systems from yeast to synaptosomes, there is
      a paucity of data from mammalian systems. To investigate fusion in rat renal
      cortical endosomes, we began by developing a fusion assay. As the immunoglobulin
      and avidin-based probes almost universally employed in fusion assays are excluded
      by the glomerular ultrafiltration barrier, it was necessary to begin by finding
      ultrafilterable probes which could serve as a fusion assay. We labeled the apical
      endosomal pathway of the renal proximal tubule by intravenous infusion of
      ultrafilterable fluorescent dextrans. Energy transfer from entrapped fluorescein
      dextran to rhodamine-dextran had a narrow concentration dependence but allowed
      fluorometric assay of endosomal fusion. The "spectroscopic ruler" property of
      energy transfer, whereby it will only occur at < 60 A, makes fusion measurements
      unequivocal. The energy transfer efficiency of fluorometric (48 +/- 1%) and flow
      cytometry (57 +/- 1%) assays were close to the theoretical optimum (57%). Energy
      transfer is detected as a decrease in fluorescence of the fluorescein donor and
      an increase in fluorescence of the rhodamine acceptor. Our endosomal fusion assay
      was utilized to determine the optimal conditions for fusion of rat renal cortical
      light endosomes and heavy endosomes. Independent measurements of fluorescein
      dextran and rhodamine-dextran on an endosome-by-endosome basis using dual-beam
      two-color flow cytometry demonstrated that each fusion event involves multiple
      endosomes rather than a single pair of endosomes. Electron microscopy analysis
      demonstrated that the average vesicle diameter was five times larger in the fused
      heavy endosomal fractions compared with control fractions without fusion. Hence,
      fusion of mammalian renal cortical endosomes reconstituted in vitro is consistent
      with multiple fusion events dubbed superfusion.

PMID- 7810691
TI  - Role of CD11a and CD11b in ischemic acute renal failure in rats.
AB  - Leukocytes, particularly neutrophils, have been implicated in ischemic
      reperfusion organ injury (IRI). However, their role in kidney IRI is
      controversial. Leukocytes express the adhesion molecules CD11/CD18 on their
      surface, which mediate many functions that can lead to tissue damage. To
      determine the role of CD11a and CD11b in IRI in the kidney, uninephrectomized
      Sprague-Dawley rats were pretreated with monoclonal antibodies (MAbs) directed
      against CD11a and CD11b or control MAbs. The serum creatinine (SCr), complete
      blood count, and kidney histopathological damage scores (PDS) (scale: 0-4) were
      assessed prior to and 24 h after 60 min of ischemia. Mean SCr 24 h after ischemia
      was significantly decreased in the anti-CD11a- and -CD11b-treated group compared
      with the control MAb-treated group (2.5 +/- 0.3 mg/dl vs. 3.4 +/- 0.2 mg/dl, P <
      0.05). PDS were also reduced in the CD11a and CD11b group compared with controls
      (2.7 +/- 0.2 vs. 3.5 +/- 0.1, P < 0.001). These data show that the CD11/CD18
      leukocyte adhesion pathway plays a role in mediating ischemic acute renal failure
      in rats.

PMID- 7810690
TI  - Angiotensin II regulates H(+)-ATPase activity in rat cortical collecting duct.
AB  - Angiotensin II (ANG II) plays an important role in the regulation of solute
      transport in the kidney, and its effect on proximal tubule sodium and fluid
      transport has been studied extensively. Although there is evidence that ANG II
      receptors are present also in the distal nephron and collecting duct, little is
      known about the physiological role of ANG II in these segments of the renal
      tubule. Preliminary studies in our laboratory suggest that ANG II may have both
      structural and functional effects on intercalated cells in the cortical
      collecting duct (CCD). Therefore, the present study examines the effect of ANG II
      on H(+)-adenosinetriphosphatase (H(+)-ATPase) and H(+)-K(+)-ATPase activity in
      individual CCD segments microdissected from collagenase-treated rat kidneys. The
      H(+)-ATPase was measured as bafilomycin-sensitive ATPase activity, and H(+)-K(+)
      ATPase was measured as Sch-28080-sensitive ATPase activity, by a fluorometric
      microassay. Preincubation of CCD segments with ANG II, 10(-10)-10(-5) M, caused a
      dose-dependent decrease in H(+)-ATPase activity with maximum inhibition at 10(-8)
      M of ANG II. The inhibitory effect of ANG II was abolished when tubules were
      incubated with ANG II in the presence of 10(-6) M losartan, indicating that the
      inhibition was mediated via specific AT1 receptors. The AT2-receptor antagonist,
      PD-123319, had no effect on the ANG II-mediated inhibition of H(+)-ATPase
      activity. Preincubation of CCD segments with 10(-10) or 10(-7) M ANG II had no
      effect on H(+)-K(+)-ATPase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7810692
TI  - Determinants of intrarenal oxygenation. I. Effects of diuretics.
AB  - To study renal cortical and medullary oxygen tensions, we used sensitive Clark
      type O2 microelectrodes, inserted by micromanipulators into the cortex and
      medulla of kidneys of anesthetized rats. As previously reported, under basal
      conditions, medullary PO2 was significantly lower than cortical PO2. Furosemide,
      which inhibits reabsorptive transport in the medullary thick ascending limb,
      increased medullary PO2 from 16 +/- 4 to 35 +/- 4 mmHg (P < 0.0005) without
      altering cortical PO2. This effect, reproduced by ethacrynic acid and bumetanide,
      was selective for loop diuretics and was directly due to decreased tubular O2
      consumption, since medullary blood flow was remarkably reduced by furosemide (-28
      +/- 6% from baseline, P < 0.0001, as measured by a laser-Doppler probe). By
      contrast, acetazolamide, which decreases proximal tubule metabolism, selectively
      increased cortical PO2. These data are, in general, consistent with tubular
      metabolism as a major determinant of intrarenal oxygenation and suggest, in
      particular, that medullary reabsorptive work is at least in part responsible for
      renal medullary hypoxia.

PMID- 7810693
TI  - Determinants of intrarenal oxygenation. II. Hemodynamic effects.
AB  - To study hemodynamic effects on intrarenal oxygenation, O2 microelectrodes were
      inserted into rat kidneys. In a previous study [M. Brezis, Y. Agmon, and F. H.
      Epstein. Am. J. Physiol. 267 (Renal Fluid Electrolyte Physiol. 36): F1059-F1062,
      1994], we showed that tubular metabolism is a major determinant of intrarenal
      oxygenation, in part responsible for medullary hypoxia observed under basal
      conditions. Acute hypotension (by controlled hemorrhage, aortic ligation, or
      nitroprusside infusion) paradoxically increased medullary PO2 (from 21 +/- 2 to
      39 +/- 2 mmHg, P < 0.001) while decreasing cortical PO2 (from 46 +/- 2 to 32 +/-
      3 mmHg, P < 0.001), abolishing corticomedullary gradients of oxygen. Laser
      Doppler studies indicated that, while cortical blood flow was reduced during
      hypotension, medullary blood flow was unchanged or increased. The increase in
      medullary PO2 induced by hypotension was abolished by prior administration of
      furosemide, suggesting that during hypotension, reduced glomerular filtration
      rate (GFR), distal delivery, and reabsorption result in decreased oxygen
      utilization. Acute infusions of atriopeptin III (0.1-1 microgram.kg-1.min-1)
      decreased both cortical PO2 (from 61 +/- 2 to 55 +/- 2 mmHg, P < 0.001) and
      medullary PO2 (from 15 +/- 1 to 7 +/- 1 mmHg, P < 0.001), consistent with
      atriopeptin-induced increases in GFR and tubular reabsorptive work. These data
      suggest that medullary oxygen availability increases during renal hypoperfusion
      and may decrease during renal vasodilation.

PMID- 7810694
TI  - Abnormal regulation of renal proximal tubule Na(+)-K(+)-ATPase by G proteins in
      spontaneously hypertensive rats.
AB  - Enhanced salt reabsorption by the kidney, which may arise from impaired
      regulation of proximal tubule Na(+)-K(+)-ATPase activity, has a central role in
      the pathogenesis of essential hypertension. Guanine nucleotide binding proteins
      (G proteins) are involved in many regulatory pathways and have been implicated in
      the regulation of proximal tubule Na(+)-K(+)-adenosinetriphosphatase (ATPase)
      activity. The present study was designed to evaluate further the regulation of
      Na(+)-K(+)-ATPase activity by G proteins in proximal tubule suspensions from
      Wistar-Kyoto rats (WKY) and to determine whether such regulation is abnormal in
      spontaneously hypertensive rats (SHR). Cholera toxin (CTX) inhibited Na(+)-K(+)
      ATPase activity by approximately 40% in WKY but had no effect on Na(+)-K(+)
      ATPase activity in SHR. In WKY, pretreatment of tubules with pertussis toxin
      (PTX), followed by the application of dopamine, inhibited Na(+)-K(+)-ATPase
      activity significantly, compared with the inhibition produced by dopamine alone.
      In SHR, dopamine alone did not inhibit Na(+)-K(+)-ATPase activity. However, in
      the presence of PTX, dopamine inhibited Na(+)-K(+)-ATPase activity significantly.
      These studies indicate that the renal proximal tubule Na(+)-K(+)-ATPase in WKY is
      regulated by both a PTX- and CTX-sensitive G protein(s) and that this regulation
      is abnormal in SHR. Such a defect could cause enhanced sodium reabsorption in SHR
      and contribute to the pathogenesis of hypertension in this model.

PMID- 7810695
TI  - Differential effects of extracellular anions on renin secretion from isolated
      perfused rat kidneys.
AB  - We investigated the relevance of anions for the regulation of renin secretion
      from the kidneys. For this purpose we measured renin release from isolated rat
      kidneys that were perfused with medium containing either 120 mmol/l (normal)
      chloride or 95 mmol/l of isethionate, acetate, or nitrate anions in exchange for
      equimolar amounts of chloride. Lowering the extracellular chloride concentration
      by either of these maneuvers significantly enhanced renin secretion rates (RSR)
      at a perfusion pressure of 100 mmHg. Increasing pressure above 100 mmHg inhibited
      renin release in the presence of isethionate and acetate but not with nitrate
      anions. The renin stimulatory effects of isethionate and acetate but not that of
      nitrate anions disappeared in the presence of bumetanide (100 mumol/l), an
      inhibitor of macula densa chloride transport. Activation of renin secretion by
      isethionate and acetate was blunted with 100 pmol/l angiotensin II (ANG II),
      whereas tenfold higher concentrations of ANG II were required to attenuate the
      effect of nitrate ions. The amount of renin released in the presence of nitrate
      was fully additive to RSR values obtained with maximally effective doses of
      isoproterenol. These findings are consistent with the idea that impermeant anions
      such as isethionate and acetate enhance renin secretion from the kidneys
      predominantly via the tubular macula densa mechanism. The stimulatory influence
      of membrane-permeable nitrate anions appears to involve additional pathways and
      is mediated by a decreased calcium sensitivity of the renin secretory process
      rather than resulting from an adenosine 3',5'-cyclic monophosphate-dependent
      action.

PMID- 7810696
TI  - Renal hypertrophy is associated with upregulation of TGF-beta 1 gene expression
      in diabetic BB rat and NOD mouse.
AB  - Renal hypertrophy is an early feature of diabetes, and it may predispose the
      kidney to the eventual development of parenchymal dysfunction. Since we have
      previously demonstrated that short-term culture in high glucose concentration
      stimulates production of transforming growth factor-beta 1 (TGF-beta 1) in
      proximal tubular and glomerular mesangial cells, we postulated that this
      cytokine, which has potent regulatory effects on cellular growth and
      extracellular matrix production, is important in mediating diabetic renal
      disease. In this study we evaluated the gene and protein expression of TGF-beta 1
      in the kidney of two rodent models of spontaneous insulin-dependent diabetes
      mellitus [the biobreeding (BB) rat and the nonobese diabetic (NOD) mouse]. In
      association with the appearance in both models of significant renal hypertrophy,
      TGF-beta 1 mRNA levels were increased threefold in the kidney of the diabetic BB
      rat after 3 days of diabetes and also threefold after 7-9 days in the NOD mouse.
      There was no increase in TGF-beta 1 transcripts in the livers of the diabetic
      animals, suggesting that this response is tissue specific. Immunohistochemical
      studies revealed that TGF-beta 1 protein is concordantly elevated in the cortical
      tubular cells of the diabetic kidney in both models. These results suggest that
      the stimulated expression of renal TGF-beta is an early manifestation of the
      involvement of the kidney by diabetes. Whether increased TGF-beta production in
      the diabetic kidney is a key promoter of diabetic renal manifestations (e.g.,
      hypertrophy) deserves additional studies.

PMID- 7810697
TI  - Physiological and structural responses to chronic experimental renal allograft
      injury.
AB  - Chronic rejection necessitates a return to dialysis or retransplantation for a
      significant number of patients with renal allografts. Although alloresponses
      between donor organ and recipient importantly determine this process, the
      detailed immunologic processes and organ physiology of chronic rejection are
      unclear; in consequence its mechanism and therapy are uncertain. A model of
      chronic rejection in the rat was used to examine several facets of this process.
      Fisher-to-Lewis (F-L), allogeneic, and Lewis-to-Lewis (L-L), syngeneic, renal
      transplants were performed in nephrectomized recipients. All rats were treated
      with cyclosporin A (5 mg.kg-1.day-1) for 10 days from the time of grafting. At 6
      wk, allogeneically grafted animals had a higher protein excretion rate (F-L, 47
      +/- 30 mg/day; L-L, 17 +/- 6 mg/day; P < 0.05) and an increase in glomerular
      capillary pressure (F-L, 69 +/- 5 mmHg; L-L, 58 +/- 8 mmHg; P < 0.05) and
      fractional cortical interstitial volume (F-L, 29.8 +/- 4.3%; L-L, 19.5 +/- 4.0%;
      P < 0.01). This model of chronic rejection is characterized by glomerular
      capillary hypertension, proteinuria, and cortical interstitial expansion. Because
      these findings are also present in other models of chronic renal injury,
      mechanisms in addition to alloresponses may operate in chronic rejection.

PMID- 7810698
TI  - Proteinuria and impaired glomerular permselectivity in uninephrectomized fawn
      hooded rats.
AB  - Previous studies of glomerular permselectivity have indicated that both size
      selectivity and charge selectivity changes play a role in the pathogenesis of
      proteinuria. In this study, we measured Ficoll sieving coefficients, hemodynamic
      parameters, and urinary protein excretion rates in the FHH strain of fawn-hooded
      rats. These animals spontaneously develop systemic and glomerular hypertension,
      proteinuria, and focal and segmental glomerulosclerosis at a relatively young
      age. Three groups of FHH rats were studied: two-kidney controls (2K), untreated
      uninephrectomized rats (CON-NX), and uninephrectomized rats treated with the
      angiotensin I converting enzyme inhibitor enalapril (ENA-NX). CON-NX rats had
      higher glomerular transcapillary pressures (delta P) and higher urinary excretion
      rates of both total protein (UpV) and albumin (UaV) than did 2K rats, whereas
      treatment with enalapril prevented both glomerular hypertension and the increased
      proteinuria. Ficoll sieving coefficients were significantly higher in both groups
      of NX rats compared with 2K rats only for Stokes-Einstein radii (rs) > or = 46 A.
      Fits of sieving data to pore models showed a small increase in the number of
      large, nonselective pores in NX, which was not prevented by enalapril treatment.
      Total clearances of Ficoll with rs = 36 A (the size of albumin) in CON-NX and ENA
      NX groups were unchanged compared with 2K animals. In contrast, UaV in CON-NX
      rats was more than six times that of 2K and ENA-NX rats. Across groups, UpV, UaV,
      and the ratio (UaV)/(UpV) all correlated strongly with delta P.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7810699
TI  - Potentiated 1,25(OH)2D3-induced 24-hydroxylase gene expression in uremic rat
      intestine.
AB  - 24-Hydroxylase has been considered a major enzyme regulating metabolism of
      circulating 1 alpha, 25-dihydroxyvitamin D3 [1,25(OH)2D3]. To understand the
      metabolism of 1,25(OH)2D3 in chronic renal failure, we examined 1,25(OH)2D3
      induced 25-hydroxyvitamin D3-24-hydroxylase (24-hydroxylase) gene expression in
      the intestine of uremic rats. Northern blot and dot blot analyses showed that the
      induction of duodenal 24-hydroxylase gene expression was 2.0- to 3.8-fold greater
      in uremic rats than in sham-operated rats (P < 0.05, Student's t-test) at 6 h
      after 1,25(OH)2D3 administration. Gene induction of calbindin D9k by 1,25(OH)2D3
      was not augmented in uremic group. In situ hybridization analysis revealed that
      the induction of 24-hydroxylase mRNA by 1,25(OH)2D3 was observed exclusively in
      the columnar epithelium of the crypt and the lower part of the villi, suggesting
      that the stage of epithelial cell differentiation is a major determinant of
      1,25(OH)2D3-induced 24-hydroxylase gene expression. In uremia, 1,25(OH)2D3
      induced 24-hydroxylase gene expression was accelerated selectively, possibly
      because of poorly differentiated epithelial cells.

PMID- 7810700
TI  - Anatomic pairing of afferent arterioles and renin cell distribution in rat
      kidneys.
AB  - Close afferent arteriolar (AA) connectivity is a prerequisite for hemodynamic
      interaction between superficial rat nephrons. Studies were conducted in rat,
      mouse, rabbit, and human renal vasculatures obtained by an HCl maceration
      microdissection technique to document the extent of AA connectivity. In rat
      kidneys, we assessed the possibility for a slow component of internephron
      coupling, as reflected by arteriolar renin cell distribution after specific
      immunostaining for renin. In the four species examined, 51% (human) to 60%
      (mouse) of total AA populations were organized as vascular units consisting of
      mostly two AA sharing a common origin and a connecting arterial segment. In rat
      AA pairs, branch lengths were significantly correlated, suggesting coordinated
      arteriolar growth. The sum of AA branch lengths averaged 278 +/- 6 microns. Rat
      arteriolar renin status, ranging from no renin cells to renin-recruited
      midafferent arterioles, distributed in a significantly nonrandom fashion within
      AA pairs, and 52% of the pairs had equal renin status. Hence, AA pairing is a
      consistent anatomic characteristic of mammalian kidneys and may constitute an
      optimal vascular design for hemodynamic as well as endocrine interactions.

PMID- 7810701
TI  - Transforming growth factor-beta expression in macrophages during
      hypercholesterolemic states.
AB  - Macrophage infiltration into the glomerular mesangium is a prominent feature of
      various glomerulopathies. Recent evidence suggests that infiltrating macrophages
      may play a role in propagating initial glomerular injury to the development of
      glomerulosclerosis via transforming growth factor-beta (TGF-beta)-stimulating
      matrix accumulation. Rats with the acute puromycin aminonucleoside (PA) nephrosis
      exhibit an elevated gene expression of glomerular TGF-beta 1; however, the
      cellular origin of this upregulation is unknown. Using polymerase chain reaction
      (PCR), we detected that the TGF-beta 1 isoform is expressed in glomerular
      macrophages isolated from experimental rats made hypercholesterolemic by either
      diet or by induction of PA nephrosis. Peritoneal macrophages from nephrotic or
      dietary-hypercholesterolemic animals also exhibited a significant increment in
      the expression of TGF-beta 1 mRNA on Northern analysis, in contrast to similar
      cells obtained from normal control rats. PCR analysis of glomerular RNA also
      detected the expression of the TGF-beta 2 mRNA isoform. TGF-beta 2 mRNA
      expression was not observed in isolated glomerular macrophages from either
      glomeruli of PA-nephrotic rats or from glomeruli of animals with dietary
      hypercholesterolemia. Expression of the TGF-beta 3 mRNA isoform was only observed
      by PCR in J774 A.1 cells. Thus the as a cellular source for the enhanced
      expression of TGF-beta 1 during the acute nephrotic phase of our toxic,
      progressive glomerulopathy model and within several days of inducing only
      hypercholesterolemia by dietary means.

PMID- 7810704
TI  - Role of renal dopamine D1 receptors in natriuresis induced by calcium channel
      blockers.
AB  - The direct tubular natriuretic effect of calcium channel blockers (CCBs) may be
      due to an interaction between CCBs and a renal tubular dopamine receptor. We
      therefore studied the effects of two chemically unrelated CCBs, diltiazem and
      isradipine, infused into the right renal artery of 5% saline-loaded anesthetized
      rats alone or in the presence of a D1 antagonist, SKF-83742. Isradipine (0.03
      microgram.kg-1.min-1) or diltiazem (20 but not 10 micrograms.kg-1.min-1) alone
      produced an increase in urine flow and an approximate doubling of absolute and
      fractional sodium excretion, which was not seen in the left kidney or in the
      control animals (analysis of variance, Scheffe's test, P < 0.05). SKF-83742 alone
      given systemically or into the right renal artery did not affect these parameters
      but did block the actions of diltiazem or isradipine. There was no change in mean
      arterial pressure, renal blood flow, or glomerular filtration rate in any of the
      experiments. In additional studies, we found that a combined infusion of dopamine
      (0.1 microgram.kg-1.min-1) and diltiazem (10 micrograms.kg-1.min-1) (doses that
      by themselves did not alter renal function) produced a twofold or greater
      increase in urine flow and absolute and fractional sodium excretion; glomerular
      filtration rate was not significantly changed. Intrarenal arterial CCBs, without
      a change in renal hemodynamics, produce a natriuresis that is blocked by a D1
      antagonist. Concomitant administration of diltiazem and dopamine (each in
      subeffective doses when used alone) produces a synergistic effect.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7810703
TI  - Distribution of Cl-/HCO3- exchange and intercalated cells in rabbit cortical
      collecting duct.
AB  - At least two cortical collecting duct (CCD) intercalated cell populations mediate
      HCO3- secretion and reabsorption. The present study examined the membrane
      location of intercalated cell Cl-/base exchange activity and the axial
      distribution of CCD intercalated cells. CCD were studied using in vitro
      microperfusion in CO2/HCO3(-)-containing solutions; intracellular pH was measured
      using 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein. The A-type intercalated
      cell (A cell) and B-type intercalated cell (B cell) were identified functionally
      by the absence and presence of apical Cl-/HCO3- exchange activity, respectively.
      When a 0 mM Cl-, 0 mM HCO3- luminal solution was used, removal of Cl- from the
      peritubular solution caused intracellular alkalinization in all B cells. The
      alkalinization required neither extracellular Na+ nor changes in membrane
      potential. Peritubular 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS)
      (10(-4) M) inhibited A cell but not B cell basolateral Cl-/base exchange
      activity. In comparison to studies performed with a 0 mM Cl- 0 mM HCO3- luminal
      solution, the use of a 0 mM Cl-, 25 mM HCO3- luminal solution inhibited both the
      identification and the magnitude of B cell basolateral Cl-/base exchange
      activity. When CCD from the inner and outer cortex were separately studied, only
      7% of outer CCD intercalated cells were A cells, whereas 93% were B cells. In
      contrast, in the inner CCD, 58% of intercalated cells were A cells and 42% were B
      cells. Under stop-flow conditions, outer CCD alkalinized the luminal fluid,
      whereas inner CCD acidified the luminal fluid. These results indicate that all
      CCD intercalated cells possess basolateral Cl-/base exchange activity; however, A
      cell and B cell basolateral Cl-/base exchange activity differs, at least in terms
      of sensitivity to DIDS. Furthermore, there is axial heterogeneity in both
      intercalated cell type and function.

PMID- 7810702
TI  - Association and interactions of GTP-binding proteins with rat medullary H(+)
      ATPase.
AB  - Guanosine 5'-triphosphate (GTP)-binding proteins (G proteins) are expressed in a
      heterogeneous manner in the mammalian kidney. In particular, cells of the
      medullary collecting tubule demonstrate a complex pattern of G protein expression
      both between cell types and between the polarized surfaces of individual cells.
      Intercalated cells expressing the H(+)-ATPase are also prevalent in this nephron
      segment. To examine interactions between G proteins and the H(+)-ATPase, we
      performed immunocytochemical studies on perfusion-fixed sections of rat kidney
      using polyclonal anti-G protein antibodies and E11, a mouse monoclonal antibody
      to the 31-kDa subunit of the vacuolar H(+)-ATPase. G alpha s subunits were
      consistently not associated with cells containing the H(+)-ATPase in this nephron
      segment, whereas G alpha i-2, G alpha i-3, and G alpha q/11 were. Some
      intercalated cells that stained prominently for the proton pump in the apical
      membrane did not, however, stain for any G protein alpha-subunit. We prepared
      medullary membrane vesicles highly enriched for the H(+)-ATPase to examine
      possible functional interactions of G proteins with the H(+)-ATPase by the
      acridine orange method. These vesicles were also highly enriched for G protein
      subunits. Proton transport was significantly increased in the presence of
      guanosine 5'-O-(3-thiotriphosphate), and this held true in the absence of
      chloride. This excludes an effect on chloride conductance indirectly stimulating
      the H(+)-ATPase. Guanine nucleotides did not affect the proton leak of the
      vesicles. Thus some G proteins are associated with the H(+)-ATPase and can
      regulate its function; however, the particular G proteins involved remain to be
      identified.

PMID- 7810705
TI  - The microtubule network of renal epithelial cells is disrupted by ischemia and
      reperfusion.
AB  - Ischemia results in alterations in the integrity of the plasma membrane of renal
      epithelial cells, changes in cell polarity, and initiation of cell division.
      Because microtubules are implicated in these processes, we examined the effects
      of ischemia and reperfusion on the microtubular cytoskeleton in rat kidney. Major
      alterations in the microtubule network of S3 proximal tubules were detected after
      40 min of ischemia followed by 1 h of reperfusion. There was fragmentation of
      microtubules and considerably less intense staining with antitubulin antibodies
      than with normal kidneys. Some thick ascending limbs of Henle close to medullary
      vascular bundles showed a variable loss of tubulin staining. After 24 and 48 h of
      reperfusion, tubulin labeling was again present in most proximal tubule cells in
      contact with the basement membrane but was not detectable in exfoliated cells.
      Numerous mitotic figures were present in kidneys 48 h after reperfusion. Kidneys
      subjected to 40 min of ischemia without reperfusion and contralateral kidneys
      studied after 1 h of reperfusion showed only mild microtubular disruption.
      Because of the established role of microtubules in the generation and maintenance
      of epithelial cell polarity, their loss may contribute to structural changes that
      occur after ischemia and reperfusion.

PMID- 7810706
TI  - H+ secretion in rabbit mesonephric collecting tubule.
AB  - The mesonephros, the precursor of the metanephros, the definitive kidney, is the
      functional excretory organ in the 12- to 20-day-old rabbit fetus. It is believed
      to acidify allantoic fluid. To determine whether H+ excretion occurs in the
      distal nephron, we examined isolated perfused mesonephric collecting tubules by
      microcalorimetry and pH-sensitive fluorescent dyes. Collecting tubules secreted
      H+ (absorbed HCO3-) at rates twice those observed in the mature outer medullary
      collecting duct (OMCD) of the metanephric kidney. H+ secretion was not inhibited
      by ouabain (18.5 +/- 2.2 vs. 16.7 +/- 4.0 pmol.min-1.mm-1; n = 7, P = NS) but was
      reversibly inhibited by removing Cl- from the bathing solution (15.1 +/- 2.3 to 
      0.6 +/- 3.7 to 15.5 +/- 1.1 pmol.min-1.mm-1; n = 5, P < 0.05); luminal
      application of N-ethylmaleimide (NEM), an inhibitor of the H(+)-ATPase, also
      inhibited H+ secretion (n = 2). These results suggested that H+ secretion in the
      mesonephric collecting tubule is mediated by transporters similar to those of the
      OMCD. To test this hypothesis, we stained collecting tubules from 15-20 day
      embryos with 6-carboxyfluorescein (6-CF) diacetate to identify intercalated-like
      cells or perfused them with 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein
      acetoxymethyl ester (BCECF-AM) to measure intracellular pH (pHi). We found that
      139 +/- 15 cells/mm concentrated 6-CF or BCECF, consistent with the phenotype of
      metanephric intercalated cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7810707
TI  - Expression of acid-base-related proteins in mesonephric kidney of the rabbit.
AB  - The mesonephric kidney, precursor to the metanephric kidney, comprises 30-50
      nephrons, each with a glomerulus and proximal, distal, and collecting tubules.
      Although two different cell types have been identified in the mesonephric
      collecting tubule, no relationship to cells of the metanephric collecting duct
      has been established. To characterize expression of some of the acid-base-related
      proteins, we assayed for carbonic anhydrase (CA) activity and performed
      immunocytochemistry in mesonephroi from 15- to 20-day-old fetal rabbits. From
      total RNA, we detected expression of CA II and CA IV mRNA. Microdissected
      proximal and collecting tubules abundantly expressed both CA II and CA IV, at
      least to the extent observed in mature metanephric proximal tubules and
      collecting ducts. Histochemistry confirmed the expression of CA activity in these
      segments; in the collecting tubule, 28% of the collecting tubule cells were CA
      rich. Most CA-rich cells showed apical H(+)-ATPase and basolateral band 3 anion
      exchanger staining consistent with the findings in mature H(+)-secreting (alpha)
      intercalated cells of the metanephric collecting duct. CA-negative cells could be
      labeled with an antibody that identifies mature metanephric principal cells. Thus
      the mesonephric collecting tubule has many cells resembling mature alpha
      intercalated cells and a majority of cells resembling principal cells. The
      similarity to the metanephric collecting duct suggests that the lineages of
      metanephric alpha-intercalated and principal cells may be closely related to
      those of the mesonephros.

PMID- 7810708
TI  - Extracellular ATP increases intracellular calcium in rat terminal collecting duct
      via a nucleotide receptor.
AB  - Recent studies in a variety of cell types have revealed several receptor subtypes
      that bind ATP and trigger increases in intracellular Ca2+ concentration
      ([Ca2+]i). The present studies were aimed at determining whether similar
      receptors are present in the rat terminal inner medullary collecting duct (IMCD).
      [Ca2+]i was measured using fura 2 in tubules dissected from collagenase-treated
      rat kidneys. ATP (1-100 microM) caused a rapid increase in [Ca2+]i with a
      prolonged late phase after an initial peak. A similar rise was observed in
      tubules exposed to UTP or to the poorly hydrolyzable analogue, adenosine 5'-O-(3
      thiotriphosphate) (ATP gamma S). In contrast, agonists that bind P2x, P2y, P2z,
      and P2t purinergic receptors did not affect [Ca2+]i. Removal of extracellular
      Ca2+ inhibited the response to ATP by approximately 50% with obliteration of the
      late phase. Furthermore, indomethacin attenuated the rise in [Ca2+]i produced by
      ATP. Adenosine analogues also increased [Ca2]i apparently by binding to distinct
      adenosine receptors rather than to the ATP receptor. We conclude that there is a
      nucleotide receptor in the rat terminal IMCD, which, when occupied, mobilizes
      intracellular Ca2+.

PMID- 7810709
TI  - Effects of endothelium-derived nitric oxide on skin and digital blood flow in
      humans.
AB  - The effects of NG-monomethyl-L-arginine (L-NMMA) on total finger and forearm, and
      dorsal finger and forearm skin, blood flows were studied in the basal state and
      during reflex sympathetic vasoconstriction in normal subjects. Total flows were
      measured by venous occlusion plethysmography and skin flows by laser-Doppler
      flowmetry (LDF). L-NMMA in doses of 2, 4, and 8 microM/min given by constant
      infusion via a brachial artery catheter significantly decreased finger blood
      flow, forearm blood flow, and vascular conductances. At 8 microM/min, total
      finger blood flow decreased 38.4% and forearm blood flow decreased 24.8%. Dorsal
      finger and forearm skin LDF were also significantly decreased (25 and 37% at 8
      microM/min). Body cooling significantly decreased finger blood flow (73.6%),
      vascular conductance, and finger LDF (59.7%). L-NMMA had no effect on total
      finger blood flow or dorsal finger LDF during body cooling. Nitric oxide or
      related compounds contribute to the basal dilator tone of the dorsal finger and
      forearm skin but not during reflex sympathetic vasoconstriction.

PMID- 7810711
TI  - Morphometry of pig coronary venous system.
AB  - This is a third part of tripartite morphometric data of the pig coronary blood
      vessels, giving a complete quantitative description of the arterial tree [Kassab
      et al., Am. J. Physiol. 265 (Heart Circ. Physiol. 34): H350-H365, 1993],
      capillary network [Kassab and Fung, Am. J. Physiol. 267 (Heart Circ. Physiol.
      36): H319-H325, 1994], and venous tree (this article). Together they provide the
      quantitative anatomic foundation for coronary hemodynamics. The coronary venules
      have a unique morphology. Unlike coronary arterioles, which have cylindrical
      cross sections and a fairly constant diameter in each segment, the venules have
      approximately elliptical cross sections, are usually wavy in the longitudinal
      direction, and often converge like fingers to a hand. Measurements were made with
      the silicone elastomer casting method on five pig hearts. Data on smaller vessels
      were obtained from histological specimens by optical sectioning. Data on larger
      vessels were obtained from vascular casts. Arcading veins and anastomoses on the
      epicardial surface have a unique topology. Data on the number of vessels in each
      order, the major and minor axes, length, connectivity matrix, and the fractions
      of the vessels of a given order connected in series in all orders of vessels of
      the sinusal and thebesian veins are presented. It is shown that of the blood in
      the coronary blood vessels of a pig heart 27.4% is in the arteries (> 200
      microns), 37.1% is in veins (> 200 microns), and 35.5% is in microcirculation (<
      200 microns), of which 89.4% is in the capillaries.

PMID- 7810710
TI  - CPT-1 inhibition by etomoxir has a chamber-related action on cardiac sarcoplasmic
      reticulum and isomyosins.
AB  - To characterize the effect of an altered substrate utilization for cardiac
      sarcoplasmic reticulum (SR) Ca2+ transport, normotensive rats were treated for 5
      wk with 15 mg.kg-1.day-1 enantiomeric etomoxir, which inhibits mitochondrial
      carnitine palmitoyltransferase-1 (CPT-1) and fatty acid synthesis. Ca2+ uptake
      rates of left and right ventricular homogenates were differentially (P < 0.05,
      two-way analysis of variance) increased by 38 and 13%, respectively. Increased (P
      < 0.05) transport rates were also observed in the presence of ryanodine. The
      differences were considerably reduced in the protein kinase A-stimulated state.
      The levels of phosphorylated phospholamban (PLB) and troponin I as well as
      immunoreactive PLB were not affected. By contrast, phosphoenzyme levels (E-P) of
      the SR Ca2+ pump were increased in left ventricular (LV) homogenates. Values of
      LV E-P and Ca2+ uptake were linearly correlated (P < 0.05) with the myosin V1
      proportions in control (31.7 +/- 1.8% V1) and treated (58.3 +/- 2.5% V1) rats.
      Thus in the left ventricle the metabolic influences have a coordinated action on
      two distinct proteins involved in relaxation or contraction. The chamber-specific
      differences in SR function suggest a more pronounced effect of etomoxir in
      functional states characterized by a reduced Ca2+ transport rate and myosin V1
      proportion.

PMID- 7810712
TI  - Use of MQAE for measurement of intracellular [Cl-] in cultured aortic smooth
      muscle cells.
AB  - A novel fluorescent indicator, N-[ethoxycarbonylmethyl]-6-methoxy-quinolinium
      bromide (MQAE), was used to measure intracellular chloride concentration ([Cl-]i)
      in primary cultures of rat aortic smooth muscle cells (VSMC). The hydrolytic and
      fluorescent properties of the dye were characterized. The intracellular Stern
      Volmer constant was calculated to be 25 M-1. Cl- efflux curves were
      characteristic of saturation-type kinetics, with an apparent Michaelis-Menten
      constant value of 11 +/- 4.8 (SD) mM, a maximum velocity of 0.038 +/- 0.021 mM/s,
      and a half time (t1/2) of 9.0 +/- 3.7 min. The average efflux rate in the first
      10 min (0.023 +/- 0.004 mM/s) was reduced in the presence of either 130 microM
      4,4'-diisothiocyanato-dihydrostilbene-2,2'-disulfonic acid (H2DIDS) (0.014 +/-
      0.006, P = 0.02) or 40 microM furosemide (0.017 +/- 0.004, P = 0.04). Restoration
      of physiological extracellular chloride concentration ([Cl-]o) after zero Cl-
      resulted in net Cl- influx with a t1/2 of 3.6 +/- 1.0 min. The initial Cl- influx
      rate was reduced after exposure to furosemide, from 0.069 +/- 0.006 to 0.046 +/-
      0.008 mM/s, P < 0.002, and was reduced after exposure to H2DIDS from 0.102 +/-
      0.013 to 0.033 +/- 0.003 mM/s, P < 0.001. Furosemide reduced the steady-state [Cl
      ]i from 31.6 +/- 3.2 to 26.1 +/- 2.4 mM, P < 0.01, whereas H2DIDS had little
      effect on [Cl-]i. Our results demonstrate that MQAE can be used to measure [Cl-]i
      in primary cultures of VSMC.

PMID- 7810713
TI  - Isolation and characterization of macrovascular and microvascular endothelial
      cells from human hearts.
AB  - In vivo models to investigate mechanisms of local hemostasis in the macro- and
      microvascular coronary circulation are not available. Therefore, we established a
      culture system of human macro- and microvascular endothelial cells with high
      cellular yield and high endothelial cell purity. Microvascular endothelial cells
      from human hearts were isolated by enzymatic treatment of cardiac muscle
      preparations obtained during heart transplantation. The isolated microvessels
      were used to start cultures that were subsequently separated and purified from
      contaminating nonendothelial cells by paramagnetic beads linked to the lectin
      Ulex europaeus agglutinin I. Macrovascular endothelial cells were isolated from
      epicardial coronary arteries and purified by paramagnetic beads as well. With
      this method high purity (< 2% nonendothelial cells) was achieved as judged from
      fluorescence-activated cell sorting. Immunochemistry demonstrated the expression
      of several typical endothelial markers. The two endothelial cell types displayed
      functional heterogeneity in respect to bradykinin degradation and plasminogen
      activator inhibitor-1 activity. Thus the ability to selectively isolate and
      culture human macro- and microvascular cardiac endothelial cells provides a
      valuable tool to systematically investigate endothelial function in human hearts.

PMID- 7810714
TI  - Ventricular pacing attenuates but does not reverse cardiac atrophy and an
      isomyosin shift in the rat heart.
AB  - The heterotopically transplanted rat heart (TH) undergoes rapid muscle atrophy
      and a concurrent shift from alpha- to beta-myosin heavy chain (MHC) by 1 wk after
      surgery. In the current experiments, TH were continuously paced (420 beats/min)
      for 1 wk beginning 24 h after surgery or for 1 wk beginning 14 days after surgery
      to determine the role of increased heart rate in preventing or reversing cardiac
      atrophy. Left ventricular (LV) wet weight (283 vs. 256 mg paced vs. nonpaced) and
      protein content (32 vs. 23 mg paced vs. nonpaced, P < 0.05) were significantly
      elevated in TH paced 1 wk after surgery but were unchanged (211 vs. 198 mg and 24
      vs. 23 mg LV wet wt and protein content, respectively) in TH paced 2 wk after
      surgery. Total cardiac protein synthesis in the TH paced immediately after
      surgery was increased compared with the corresponding nonpaced hearts (5.6 vs.
      4.0 mg.mg LV wet wt-1.day-1, P < 0.05), while in the TH, where pacing was
      initiated 2 wk after surgery, it was unchanged (3.6 vs. 3.7 mg.mg LV wet wt-1.day
      1). Fractional synthesis rate was elevated in TH and was not altered by pacing.
      Pacing the TH also attenuated the shift in alpha-MHC in the first 7 days after
      surgery but did not reverse the shift 2 wk later. The increase in protein
      synthesis combined with an unchanged fractional synthesis rate suggests that
      pacing attenuates cardiac mass by decreasing protein degradation and that once
      the atrophic process is established, neither synthesis rate nor isomyosin shift
      can be altered by continuous pacing.

PMID- 7810715
TI  - Buffering of respiratory variations in venous return by right ventricle: a
      theoretical analysis.
AB  - The role of the right ventricle (RV) in buffering systemic venous return, thereby
      dampening respiratory-induced variations, left ventricular (LV) stroke volume,
      and systemic arterial pressure variations was examined using a computer model of
      the cardiovascular system. Respiration was simulated by cyclical variations in
      intrathoracic and abdominal pressures (cycle time 5 heartbeats), causing a 43-ml
      fluctuation in venous return per heartbeat (mean 71 ml) compared with
      fluctuations of 19 ml in RV stroke volume, 6 ml in pulmonary venous flow, and
      only 3 ml in LV stroke volume. On a percentage basis, the RV provided 56% of the
      total buffering of systemic venous return, the lungs another 30%, whereas the LV
      only 7%. A 10-fold increase in RV diastolic compliance increased the RV stroke
      volume variations from 26 to 57% of the venous return variations; a 10-fold
      increase in RV elastance increased them from 24 to 60%, whereas decreasing
      pulmonary arterial pressure from 28 to 10 mmHg increased them from 28 to 56%. The
      results also suggest that an underrecognized function of the RV is to buffer
      systemic venous return and thereby keep LV stroke volume relatively constant.

PMID- 7810716
TI  - Attenuation of arteriolar alpha 2-adrenoceptor sensitivity during endotoxemia.
AB  - It is well documented that adrenergic responses after endotoxin (ENDT)
      administration are greatly reduced. The hypothesis of this study is that either
      alpha 1- or alpha 2-receptor activity is attenuated and the other receptor type
      is minimally affected during ENDT shock. Reactivity of the arterioles of left
      cremaster muscles of male Wistar rats anesthetized with pentobarbital sodium was
      studied using videomicroscopy. Femoral mean arterial pressure and first-, second
      , third-, and fourth-order arteriolar diameters were measured. In group I, the
      decreases in arteriolar diameter and half-maximal effective dose (ED50) values
      with increasing phenylephrine concentration (alpha 1-adrenergic receptor agonist)
      were similar in all four branching orders before and after ENDT. In group II, the
      decreases in arteriolar diameter with increasing clonidine concentrations (alpha
      2-adrenergic receptor agonist) were effectively attenuated by ENDT, and ED50
      values were increased above control in all four branching orders. In group III,
      idazoxan (alpha 2-receptor antagonist) effectively blocked the vasoconstrictor
      effects of clonidine but did not affect the responses to phenylephrine before or
      after ENDT in all four arteriolar orders. In group IV, prazosin (alpha 1
      adrenergic receptor antagonist) blocked the vasoconstrictor effects of
      phenylephrine before and after the administration of ENDT. However,
      vasoconstriction due to clonidine post-ENDT even at maximal dosage (10(-3) M),
      was greatly attenuated in all four branching orders as in group II. It is
      concluded that during endotoxemia the reduced adrenergic vasoconstrictor response
      of cremaster muscle arterioles is the result of attenuated activity of alpha 2
      adrenergic receptors with minimal if any effects on alpha 1-adrenergic receptor
      activity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7810717
TI  - Adenosine A1-receptor mechanisms antagonize beta-adrenergic pulmonary
      vasodilation in hypoxia.
AB  - Hypoxic pulmonary vasoconstriction is refractory to beta-adrenergic receptor
      (beta-AR)-mediated pulmonary vasodilation. We hypothesized that hypoxic pulmonary
      arteries release adenosine (Ado) that antagonizes beta-AR-mediated pulmonary
      vasodilation. Using isolated rat pulmonary artery rings, we investigated 1) the
      effect of hypoxia and exogenous Ado on beta-AR-mediated pulmonary vasodilation,
      2) the intracellular site of dysfunctional beta-AR-mediated pulmonary
      vasodilation in hypoxia, and 3) the Ado receptor subtype responsible for
      dysfunction of beta-AR-mediated pulmonary vasodilation. Hypoxia attenuated normal
      beta-AR-mediated pulmonary vasodilation to isoproterenol (97.5 +/- 0.8 vs. 71.5
      +/- 2.3%, P < 0.01). In contrast, forskolin induced the same vasorelaxation in
      hypoxic pulmonary rings as controls (P = 0.09). Incubation of normoxic rings with
      Ado attenuated the vasorelaxation response induced by beta-AR stimulation (71.5
      +/- 5.9%, P < 0.01), similar to the effect observed in hypoxia. Both nonspecific
      Ado receptor blockade (8-sulfophenyl-theophylline) and specific A1-receptor
      blockade (8-cyclopentyl-1,3-dimethylxanthine) restored the vasorelaxation
      response of hypoxic rings induced by beta-AR stimulation (93.3 +/- 2.3 and 92.2
      +/- 2.8%, P < 0.01). The effects of hypoxia and Ado were reproduced by a specific
      A1 agonist (2-chloro-N6-cyclopentyladenosine), demonstrating impaired
      vasorelaxation induced by beta-AR stimulation in normoxia (70.6 +/- 4.5%, P <
      0.01). From these data, we conclude that hypoxia antagonizes beta-AR-mediated
      pulmonary vasodilation via an Ado A1-receptor mechanism.

PMID- 7810718
TI  - Skeletal muscle phosphate metabolism abnormalities in volume-overload
      experimental heart failure.
AB  - We studied skeletal muscle phosphate metabolism abnormalities to examine their
      contribution at an early stage of congestive heart failure (CHF) in rats with
      aortocaval fistula (ACF) 4 wk after the procedure. In a group of 26 rats (13 with
      ACF and 13 sham operated), we assessed the degree of CHF. The ACF produced a
      significant rise in heart weight and plasma atrial natriuretic peptide. In a
      second group of 26 rats (13 ACF and 13 sham operated), we performed 31P-magnetic
      resonance spectroscopy in the gastrocnemius muscle during motor activity produced
      by electrical stimulation. The rate of phosphocreatine depletion, expressed by
      its initial slope, was higher in the ACF rats compared with controls (0.078 +/-
      0.01 vs. 0.041 +/- 0.007; P < 0.03). pH and ATP decreased and phosphodiesters
      increased in all rats during electrical stimulation, with no difference between
      ACF rats and controls. The kinetics of phosphocreatine recovery were not
      different between ACF rats and controls. Together with previous studies, our
      present results suggest that muscle metabolism abnormalities in CHF may vary
      according to the experimental model and may be observed early in the course of
      the disease.

PMID- 7810719
TI  - Regulation of ANP secretion by endothelin-1 in cultured atrial myocytes:
      desensitization and receptor subtype.
AB  - We examined endothelin-1 (ET-1) binding and ET-1-regulated atrial natriuretic
      peptide (ANP) secretion in primary cultures of adult rat atrial myocytes. ET-1
      binding was analyzed as a reversible bimolecular reaction, with bimolecular
      association rate constant = 1.9 x 10(9) M-1.h-1, dissociation rate constant =
      0.028 h-1, and a dissociation constant, calculated from these values = 0.015 nM.
      ET-1 increased ANP secretion with a one-half effective concentration (EC50) of
      0.62 nM, which correlated with EC50 receptor occupancy under equivalent
      experimental conditions (0.75 nM). The secretory response rapidly desensitized
      (half-time = 10 min at 10 nM ET-1). The time courses for ET-1 binding, ET-1
      stimulated secretion, and desensitization were all comparable. Recovery from
      desensitization was slow and paralleled the recovery of 125I-labeled ET-1
      binding. The ETA receptor subtype-selective antagonist, BQ-123, inhibited 125I-ET
      1 binding and ET-1-activated ANP secretion with high affinity, whereas the ETB
      selective agonists, endothelin-3 and sarafotoxin S6c, inhibited binding with low
      affinity and did not effectively stimulate ANP secretion. We conclude that 1) ET
      1 can stimulate ANP secretion by direct action on the atrial myocytes; 2) primary
      cultures of adult rat atrial myocytes express only the ETA receptor subtype; 3)
      the ANP secretory response to ET-1 desensitizes rapidly but recovers slowly; and
      4) occupation of the ETA receptors by ET-1 initiates the unidirectional sequence
      of receptor activation, signal transduction, ANP secretion, and finally,
      desensitization.

PMID- 7810720
TI  - Oxidant stress increases heat shock protein 70 mRNA in isolated perfused rat
      heart.
AB  - Ischemia/reperfusion (I/R) and preconditioning of the heart by coronary artery
      occlusions increase expression of heat shock protein 70 (HSP 70). Because free
      radicals are generated during I/R, we hypothesized that the oxidant stress might
      contribute to an increased expression of HSP 70. Isolated rat hearts were
      perfused with free radical-generating systems such as xanthine/xanthine oxidase
      (X/XO), irradiated rose bengal (RB) generating singlet oxygen, and H2O2 for 15
      min followed by 30 min of recovery period. Significant decrease in developed
      pressure and coronary flow occurred after perfusion with X/XO, H2O2, and RB.
      During I/R, the developed pressure and coronary flow were 60 +/- 8 and 80 +/- 5%,
      respectively, of control, which improved significantly with superoxide dismutase.
      The expression of HSP 70 mRNA increased over 13-fold in hearts perfused with
      X/XO, 6- to 7-fold with RB, and over 5-fold with H2O2. With I/R, an over 10-fold
      increase in HSP 70 mRNA was observed, which decreased significantly in the
      presence of superoxide dismutase. These results demonstrate that oxidant stress
      directly increases HSP 70 mRNA in the rat heart. It is concluded that one of the
      potential mechanisms of expression of HSP 70 by I/R may be oxygen radicals.

PMID- 7810721
TI  - Autoregulation of cerebral blood flow: influence of local brain development and
      postnatal age.
AB  - To investigate whether the efficiency of cerebral blood flow autoregulation
      depends on local brain maturity, we examined the effect of development on the
      local autoregulatory response. We measured local brain blood flow using laser
      Doppler flowmetry and quantitative autoradiography during hemorrhagic hypotension
      and hypertension (intravenous norepinephrine) in newborn 1- to 2-day-old (P1), 7-
      to 8-day-old (P8), 16- to 18-day-old (P17), and adult rabbits. Autoregulation
      within the cortex was less efficient than within the medulla in young (P1 or P8)
      compared with older rabbits (P17 or adult). Blood pressure increased during
      development, and the autoregulatory range extended up to 10, 15, 35, and over 100
      mmHg about the normal pressure in P1, P8, P17, and adult animals, respectively.
      Acute severe hypertension readily produced focal areas of hyperemia within the
      cortex, thalamus, hippocampus, and/or cerebellum in young (P1 and P8) but not P17
      animals. Severe hypotension produced profound reductions in blood flow within the
      cortex and subcortical white matter but not within deep forebrain and brain stem
      structures. Thus the efficiency of the autoregulatory response in general
      improved with increasing age and maturity of the brain region indicating that
      immature brain is susceptible to both ischemia during hypotension and hyperemia
      during hypertension.

PMID- 7810722
TI  - Transient blood-brain barrier passage of polar compounds at low pH.
AB  - The brain uptake index (BUI) of polar 14C-labeled test compounds with molecular
      weights (MWs) of 79-70,000 was examined using the single-pass carotid injection
      technique in pentobarbital-anesthetized rats. Compounds were injected in 40 mM
      malonate, pH 2.5, and 10 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid,
      pH 7.4. BUI is defined as (14C-labeled test compound/[3H]H2O in brain)/(14C
      labeled test compound/[3H]H2O in injectate) x 100 at a 5-s decapitation time.
      Increased BUIs of compounds in pH 2.5 buffer were MW dependent with a threshold <
      5,000. BUI, extraction, and permeability-surface area product (PS) were
      significantly greater at pH 2.5 compared with pH 7.4 (P < 0.05). Washouts of
      [14C]butanol and [3H]H2O at pH 2.5 and pH 7.4 were calculated. Cerebral blood
      flow and PS increased at low pH. Other buffers, oxalate, glycine, and lactate
      were used at low pH and also increased BUIs. The duration of the blood-brain
      barrier (BBB) opening at pH 2.5 was 60 s as estimated by penetrance of the
      normally excluded dye fluorescein. A plot of BUI or PS at pH 2.5 vs. (MW)1/2
      suggests that transient BBB tight junction opening contributed to the passage of
      polar compounds at low pH.

PMID- 7810723
TI  - Nonsynchronous changes in myocardial collagen mRNA and protein during aging:
      effect of DOCA-salt hypertension.
AB  - Myocardial fibrosis has been investigated in 3-, 16-, and 24-mo-old normal rats
      and also in 24-mo-old rats subjected to deoxycorticosterone acetate (DOCA)-salt
      treatment-induced-hypertension. Collagen content was assessed both histologically
      and by hydroxyproline assay. Type I and III procollagen mRNA levels were
      quantitated by Slot Blot analyses. Aging is associated with fibrosis as shown
      both biochemically (hydroxyproline concentration in 3-, 16-, and 24-mo-old rats
      was 0.70 +/- 0.05, 0.92 +/- 0.07, and 1.57 +/- 0.13 mg/g of left ventricle,
      respectively, P < 0.05 and P < 0.0001 vs. 3 mo) and histologically. By contrast,
      type I procollagen mRNA levels decreased during aging (from -63%, P < 0.001 in 16
      mo-old rats and -51%, P < 0.01 in 24-mo-old rats vs. 3-mo-old rats) as well as
      type III procollagen mRNA levels. DOCA-salt treatment in 24-mo-old rats had no
      effect on either the degree of fibrosis or the mRNA levels. We conclude that
      nonsynchronous changes in myocardial collagen mRNA and protein occur during
      aging, indicating translational and/or posttranslational mechanisms in collagen
      regulation. Hypertension during senescence did not modify collagen deposition at
      either the protein or mRNA levels.

PMID- 7810724
TI  - Effects of oral AVP receptor antagonists OPC-21268 and OPC-31260 on congestive
      heart failure in conscious dogs.
AB  - Rapid right ventricular pacing could induce congestive heart failure in conscious
      dogs with significant increase in plasma concentration of arginine vasopressin
      (AVP) (from 1.2 +/- 0.2 to 3.4 +/- 0.6 pg/ml). In this experimental model of
      heart failure, oral administration of the selective AVP V1 receptor antagonist
      OPC-21268 significantly increased cardiac output and improved renal function
      without significant changes in serum electrolytes and hormones. Oral
      administration of the selective AVP V2 receptor antagonist OPC-31260 induced
      marked water diuresis, which resulted in significant increases in serum sodium
      concentration, plasma renin activity, and plasma concentration of AVP, although
      it did not produce hemodynamic improvement. Combined administration of OPC-21268
      and OPC-31260 showed supra-additive hemodynamic responses as well as additive
      renal and metabolic responses, i.e., it showed prolonged decrease in mean
      arterial pressure and profound increase in cardiac output. These results suggest
      that AVP plays a significant role in elevation of vascular tone through V1
      receptors and plays a major role in retaining free water through V2 receptors in
      this model of heart failure. Furthermore, combined administration of V1 and V2
      receptor antagonists could induce not only metabolic and hormonal responses but
      also more beneficial hemodynamic responses than those observed following
      treatment with V1 receptor antagonist alone.

PMID- 7810725
TI  - Systemic filling pressure in intact circulation determined on basis of aortic vs.
      central venous pressure relationships.
AB  - In the intact circulation, mean systemic filling pressure (Psf) is determined by
      applying a series of inspiratory pause procedures (IPPs) and using Guyton's
      equation of venous return (Qv) and central venous pressure (Pcv): Qv = a - b x
      Pcv. During an IPP series, different tidal volumes are applied to set Pcv at
      different values. From the linear regression between Qv and Pcv, Psf can be
      calculated as Psf = a/b. Guyton's equation can also be written as Qv = (Psf -
      Pcv)/Rsd, where Rsd is the flow resistance downstream of the places where blood
      pressure is equal to Psf. During an IPP, a steady state is observed. Therefore,
      we can also formulate the following equation for flow: Qs = (Pao - Psf)/Rsu,
      where Qs is systemic flow, Rsu is the systemic flow resistance upstream to Psf,
      and Pao is aortic pressure. Because both flows (Qs and Qv) are equal, it follows
      that Pao = Psf(1 + Rsu/Rsd) - Rsu/Rsd x Pcv. This equation implies a method to
      determine mean systemic filling pressure on the basis of Pao measurements instead
      of flow determinations. Using 22 IPPs in 10 piglets, we determined the mean
      systemic filling pressure, and we compared the values obtained from the flow
      curves with those obtained from the aortic pressure curves. The mean difference
      between the two methods was 0.03 +/- 1.16 mmHg. With the use of Pao measurements,
      the Psf can be estimated as accurately as in using flow determinations. The
      advantage of the new method is that estimation of cardiac output is not required.

PMID- 7810726
TI  - Role of endothelin-1 in neointima formation after endothelial removal in rabbit
      carotid arteries.
AB  - To investigate the role of local endothelin (ET)-1 in neointima formation, we
      performed a balloon denudation in the rabbit carotid artery. Four weeks after
      denudation, regeneration of endothelial cells was almost complete, and a marked
      intimal hyperplasia was observed. The tissue level of ET-1-like immunoreactivity
      was significantly increased even at 24 and 72 h after denudation and was 9.3
      times higher than the control group in 4 wk. On the same time course, the
      proliferating cell nuclear antigen (PCNA)-positive cells clearly appeared.
      Receptor density values for 125I-ET-1 and 125I-IRL-1620 [ET-receptor subtype B
      (ETB)-selective ligand] bindings were significantly greater in the hyperplastic
      artery without changes in dissociation equilibrium constant values. The 125I-ET-1
      binding sites not inhibited with BQ-123 [ET-receptor subtype A (ETA)-selective
      antagonist] were significantly increased in hyperplastic arteries. ETB receptors
      were more densely localized in the neointima. The chronic intravenous
      administration of BQ-123 at plasma concentrations sufficient to antagonize the
      ETA receptors had no effect on neointima formation and the appearance of PCNA
      positive cells. We concluded from all results that ET-1 would be involved in
      neointima formation after endothelial removal and that the ETA receptors would
      not play a role in this process.

PMID- 7810727
TI  - Perinatal accumulation of arterial wall constituents: relation to hemodynamic
      changes at birth.
AB  - We compared arterial growth to hemodynamic changes in the perinatal period in
      lambs. Blood pressure did not change significantly from 120 days gestation to 3
      days postpartum, when it was 45.4 +/- 1.9 mmHg; however, pressure rose to 64.8 +/
      2.5 mmHg at 21 days postpartum. Thoracic and abdominal aortic and iliac and
      carotid arterial blood flows fell > 50% after birth but returned to fetal levels
      except in the abdominal aorta by 21 days postpartum. Blood flows in mesenteric
      (BFm) and renal (BFr) arteries increased between 120 days gestation (BFr = 13.4
      +/- 1.4; BFm = 41.8 +/- 3.5 ml/min) and 140 days gestation (BFr = 25.9 +/- 1.8;
      BFm = 189 +/- 18 ml/min) and between 3 and 21 days postpartum (to BFr = 71.1 +/-
      14.3; BFm = 334 +/- 59 ml/min). Elastin accumulation accelerated at 140 days
      gestation in all arteries except the thoracic aorta, in which elastin
      accumulation was always rapid. Collagen but not DNA accumulation also accelerated
      in most arteries. Postpartum dexamethasone (0.1 mg/kg twice a day) did not affect
      abdominal aortic elastin by 10 days of age (23.9 +/- 2.7 vs. 26.4 +/- 4.1 mg for
      controls); however, dexamethasone upregulated tropoelastin mRNA in fetuses. We
      hypothesize that cortisol stimulates elastin accumulation in late gestation.
      Postnatal elastin but neither collagen nor DNA correlated with blood flow changes
      at birth (r = 0.855, P < 0.05). We infer that accumulation of elastin is
      sensitive to blood flow rates during perinatal development.

PMID- 7810728
TI  - Calcium current in rat diabetic ventricular myocytes.
AB  - The magnitude and kinetics of the L-type calcium current were compared in single
      left ventricular myocytes isolated from 8-mo-old (8M) and 19-mo-old (19M)
      genetically diabetic rats (WBN/Kob rats) and age-matched control rats. A diabetic
      state occurred at 19M but not at 8M. The left ventricular contractility was
      reduced in 19M WBN/Kob rats compared with age-matched control rats. The duration
      of the action potential was longer in 19M WBN/Kob rats than in the age-matched
      control rats. Peak inward current density was similar between diabetic rats and
      age-matched control rats. In addition, aging did not affect the current density
      at 8M or 19M. The various kinetic parameters of the L-type calcium current were
      not different between 19M diabetic and control cell types. The percent increase
      in the amplitude of the calcium current induced by isoproterenol was less in
      diabetic cells at the age of 19M, but not at the age of 8M, compared with age
      matched control cells. Forskolin (10(-5) M), intracellularly applied adenosine
      3',5'-cyclic monophosphate (5 x 10(-5) M), and guanosine 5'-[gamma
      thio]triphosphate (10(-4) M) were equally effective in increasing the current in
      19M diabetic and age-matched control cell types. The present study demonstrates
      that the basal calcium current density and kinetic parameters of the current were
      not altered. However, a decrease in response to beta-stimulation occurred in
      genetically diabetic rats compared with control rats.

PMID- 7810729
TI  - Eicosanoid production by human aortic endothelial cells in response to
      endothelin.
AB  - Endothelial cells actively regulate their environment by secreting humoral
      substances, including endothelin-1 and a variety of eicosanoids, that have local
      actions. To elucidate interactions among these local mediators, we measured
      release of cyclooxygenase and lipoxygenase pathway products of arachidonate
      metabolism by human aortic endothelial cells after incubation with endothelin-1.
      Supernatants were collected, extracted, and fractionated using high-performance
      liquid chromatography. Radioimmunoassays for eicosanoids were performed on the
      appropriate fractions. After endothelin stimulation, production of the
      prostacyclin metabolite 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha), the
      thromboxane (Tx) metabolite TxB2, and prostaglandin E2 (PGE2) were increased (307
      +/- 48, 320 +/- 91, and 315 +/- 74% of control, P < 0.05). Leukotriene B4 (LTB4)
      release was modestly increased (195 +/- 19% of control, P < 0.05). The release of
      5-hydroxyeicosatetraenoic acid (5-HETE) was increased (300 +/- 57% of control, P
      < 0.05); production of 12-HETE and 15-HETE was unchanged. Production of
      eicosanoids peaked between 30 and 120 min. Preincubation with pertussis toxin
      prevented increased production of PGE2, LTB4, and 5-HETE after endothelin-1
      stimulation; pretreatment with sphingosine had no effect. Interactions between
      endothelin and eicosanoids may be important components of the complex network
      that regulates vascular tone, coagulation, and inflammation at the local level.

PMID- 7810730
TI  - Chronic administration of angiotensin II receptor antagonist, TCV-116, in
      cardiomyopathic hamsters.
AB  - We examined whether specific blockade of the renin-angiotensin system is
      beneficial for the treatment of cardiac dysfunction in heart failure. The
      angiotensin II type-1 (AT1) receptor antagonist TCV-116 (10 mg.kg-1.day-1) or its
      vehicle was given orally to UM-X 7.1 cardiomyopathic (CM) and normal Golden
      Syrian (GS) hamsters for 8 wk. Plasma and cardiac angiotensin II levels were
      significantly higher in CM than in GS hamsters. The CM heart showed a smaller
      response of left ventricular (LV) pressure and first derivative of maximal LV
      pressure (+dP/dtmax) to the elevation of perfusion pressure (from 60 to 120
      cmH2O) in Langendorff-perfused than in GS heart. Treatment with TCV-116 did not
      affect LV function in GS but significantly improved cardiac contractility in CM
      hamsters. These results suggest that the renin-angiotensin system plays an
      important role in the development of cardiac dysfunction due to cardiomyopathy.
      Blockade of this system by the AT1 antagonist TCV-116 appears to be useful in the
      prevention of heart failure.

PMID- 7810731
TI  - Gender difference in bioassayable endothelium-derived nitric oxide from isolated
      rat aortae.
AB  - Gender differences in the production/release of endothelium-derived nitric oxide
      (EDNO) was assessed by determining the ability of intact endothelium to suppress
      serotonin- (10(-7)-10(-5) M) and phenylephrine-induced (10(-9)-(10(-5) M)
      contractions in thoracic aortae isolated from male and female Wistar rats mounted
      in organ chambers for isometric tension recording or tested in bioassay
      experiments. The endothelium suppressed these contractions significantly more in
      aortae from female than from male rats. In the bioassay, the perfusate from
      intact female thoracic aortic segments produced a significantly greater
      relaxation of the detector rings than that from the aortae isolated from male
      rats. Acetylcholine (10(-9)-10(-5) M), used to investigate agonist-induced
      release of EDNO, evoked significantly greater endothelium-dependent relaxation in
      aortae from female rats. The unstimulated release of 6-ketoprostaglandin F1 alpha
      and thromboxane B2 from intact thoracic aortic rings from male and female rats
      was not significantly different. There was no difference in smooth muscle
      reactivity to sodium nitroprusside (10(-10)-10(-6) M) in rings without
      endothelium. These results indicate that EDNO production/release is higher in
      thoracic aortae isolated from female rats.

PMID- 7810732
TI  - Metabolism of exogenously applied fructose 1,6-bisphosphate in hypoxic vascular
      smooth muscle.
AB  - Exogenously administered fructose 1,6-bisphosphate reportedly protects ischemic
      or hypoxic tissue and facilitates metabolic recovery. The mechanism of action of
      exogenous fructose 1,6-bisphosphate has been an issue of considerable debate,
      since there is a lack of direct evidence that fructose 1,6-bisphosphate can cross
      the cell membrane and act as an intermediate in glycolysis. We synthesized [1,6
      13C]fructose 1,6-bisphosphate and directly examined its cellular metabolism in
      hog carotid artery segments using 13C-nuclear magnetic resonance (NMR)
      spectroscopy. [1,6-13C]fructose 1,6-bisphosphate (2.1 mM) was metabolized by hog
      carotid artery during normoxia and hypoxia with a major metabolic product being
      [3-13C]lactate. The production of [3-13C]lactate was greater during hypoxia than
      during normoxia, indicating that fructose 1,6-bisphosphate metabolism responded
      to the energetic state of the tissue. We found that exogenously added fructose
      1,6-bisphosphate at 2.1 mM did not significantly improve the ability of hypoxic
      hog carotid artery to maintain isometric force, whereas 20 mM fructose 1,6
      bisphosphate did significantly, although modestly, improve isometric force
      maintenance. These results indicate that exogenously added fructose 1,6
      bisphosphate is capable of entering cells and serving as a glycolytic
      intermediate.

PMID- 7810733
TI  - Evidence for functionally distinct dual atrial inputs to the human AV node.
AB  - Although conventional models of the human atrioventricular (AV) node assume a
      single upper common pathway, animal studies demonstrate dual atrial inputs: an
      anterior input from the interatrial septum and a posterior input from the crista
      terminalis (running near the os of the coronary sinus in the posteroseptal
      region). We hypothesized that functionally distinct dual atrial inputs to the AV
      node also exist in humans and that the anterior input has a lower safety factor
      for impulse propagation. To evaluate this hypothesis, we examined 20 patients
      undergoing radiofrequency ablation of the slow AV nodal pathway for AV nodal
      reentrant tachycardia who underwent subsequent follow-up testing. After ablation
      near the os of the coronary sinus (and posterior to the compact AV node), 11
      patients had no residual slow pathway conduction [SP(-)], whereas 9 did [SP(+)].
      The effective refractory period of the fast AV nodal pathway (FP-ERP) and
      anterograde AV nodal Wenckebach (AVN-W) cycle length were significantly increased
      at follow-up in the SP(-) patients (FP-ERP = 336 +/- 71 vs. 387 +/- 103 ms, P =
      0.02; AVN-W cycle length = 356 +/- 74 vs. 442 +/- 118 ms, P = 0.03) but not in
      SP(+) patients. Similarly among 10 patients undergoing radiofrequency ablation of
      a right posteroseptal accessory pathway (near the os of the coronary sinus), 5
      developed impaired AV conduction: abnormal anterograde pacing-induced AVN-W cycle
      length in 4 patients and 2:1 AV nodal block in 1 patient.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7810734
TI  - Ebselen protects against ischemia-reperfusion injury in a canine model of
      myocardial infarction.
AB  - We investigated the infarct-limiting effect of a selenoorganic compound, ebselen
      [2-phenyl-1,2-benzisoselenazol-3(2H)-one], in a canine coronary artery occlusion
      reperfusion model of myocardial infarction. Ebselen, administered 1 h before
      coronary artery occlusion (50 mg/kg po), significantly reduced infarct size
      resulting from 90-min coronary artery occlusion followed by 5-h reperfusion (P <
      0.05). When we examined the relation between infarct size and plasma ebselen
      level, infarct size in dogs with plasma ebselen level > 5 microM before
      reperfusion was significantly smaller (P < 0.05) than that in dogs with plasma
      ebselen level < or = 5 microM or in the control dogs. This infarct limitation
      produced by ebselen treatment was associated with an increase in reduced
      glutathione content and a reduction in myeloperoxidase activity in the ischemic
      myocardium. No differences between the control and treated groups were found in
      hemodynamic parameters or regional myocardial blood flow in the course of the
      experiment. The findings of this study demonstrate that ebselen effectively
      reduced the myocardial ischemia-reperfusion injury associated with preservation
      of the glutathione redox state and a reduction in neutrophil infiltration into
      the ischemic myocardium.

PMID- 7810735
TI  - Gradients of epicardial strain across the perfusion boundary during acute
      myocardial ischemia.
AB  - To study the mechanical interaction between acutely ischemic and adjacent
      perfused myocardium, nonhomogeneous distributions of end-systolic epicardial
      strain were measured using an array of radiopaque beads sewn on the left
      ventricular free wall of the pig during complete left circumflex coronary artery
      occlusion. The midwall perfusion boundary, demarcated by postmortem dye
      injection, was reconstructed over the span of the epicardial array. During
      ischemia, circumferential and longitudinal shortening remained significantly
      depressed up to 13 mm outside the ischemic region near the base of the ventricle,
      up to 8-9 mm at the midventricle, but only 0-1 mm near the apex (P < 0.05).
      Gradients of circumferential and longitudinal strain across the boundary were
      significantly different during both baseline conditions and acute ischemia (P =
      0.0001). However, gradients of the change in the strain from baseline to ischemia
      were not different for the two components. These results support the concept that
      direction-dependent differences in the strain gradients across the boundary
      during ischemia were due to the preservation of the baseline regional variations
      of strain combined with a loss of systolic function in the ischemic region.

PMID- 7810736
TI  - Vulnerability of conducted vasomotor response to ischemia.
AB  - Many vasoactive substances induce two responses, a direct effect at the site of
      application and a conducted response that spreads along the vessel length. In the
      microcirculation, we find that these two components of the vasomotor response
      display quite different sensitivities to occlusion and/or ischemia. Conducted
      vasomotor responses were induced in arterioles of the hamster cheek pouch by
      micropipette application of two test agents: phenylephrine (PE), which causes a
      receptor-mediated vasomotor response, and KCl, which causes an alteration in the
      membrane potential by a simple change in the K+ gradient. Ischemia was produced
      either by total occlusion of the vascular supply, which resulted in a complete
      cessation of flow in all vessels, or by venous occlusion, which was achieved by
      gradually inflating a pressurized cuff positioned across the pedicle of the pouch
      until venous return from the pouch was arrested while the feed arterioles
      remained patent. Both types of occlusion produced ischemia, the former with low
      intravascular pressure, the latter with high intravascular pressure. During both
      types of occlusion, arterioles were initially maximally dilated and unresponsive
      to both agonists, but over a subsequent 3- to 5-min period, resting arteriolar
      tone and local responses to both agonists returned. With total occlusion, the
      conducted response to KCl returned in parallel with the local response, whereas
      the conducted response to PE was diminished or absent. With venous occlusion, the
      local responses recovered as with total occlusion, but the conducted responses to
      both PE and KCl recovered as well.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7810738
TI  - Influence of cardiac output distribution on cardiac filling pressure during rest
      and dynamic exercise in dogs.
AB  - The distribution of cardiac output (CO) between compliant and noncompliant organs
      is an important determinant of the slope of the relationship predicted between CO
      and right atrial pressure (RAP). However, curves relating CO to RAP at rest are
      shifted rightward (higher CO) and upward (higher RAP) by exercise with no change
      in slope, despite a large rise in the fraction of CO directed to noncompliant
      muscle vasculature, which is predicted to decrease the slope. We sought to test
      whether reductions in CO imposed during rest and exercise are accompanied by
      changes in its distribution that would favor constant slopes. Six dogs had
      atrioventricular block produced surgically and had blood flow transducers
      implanted on the ascending aorta and the terminal aorta. Total muscle blood flow
      (MBF) was estimated from terminal aortic flow by assuming that all of the
      increase in CO in mild dynamic exercise is directed to muscle. CO was reduced by
      lowering ventricular pacing rate at rest and during graded treadmill exercise (2
      and 4 miles/h at 0% grade). Exercise increased the fraction of CO directed to
      muscle (MBF/CO) (P < 0.001). The effect of changes in CO on MBF/CO depended on
      exercise intensity (P < 0.01). At rest, MBF/CO fell from 0.53 to 0.45 when CO was
      reduced; this is expected to reduce the slope of the measured relationship
      between CO and RAP. During exercise at 2 miles/h, MBF/CO changed little when CO
      was reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7810737
TI  - Prevention of lipid peroxidation does not prevent oxidant-induced myocardial
      contractile dysfunction.
AB  - We tested whether, with exposure to an extraneous iron-catalyzed free radical
      generating system, prevention of lipid peroxidation with U74006F, a 21
      aminosteroid, could also prevent myocardial contractile dysfunction. Rabbits
      received either U74006F (10 mg/kg iv) or vehicle (V). Thirty minutes later the
      hearts were excised and perfused by a non-recirculating Langendorff technique.
      Six U74006F- and six V-treated hearts were exposed for 7.5 min to a .OH
      generating system (H2O2 and Fe(2+)-ADP chelate). Myocardial lipid peroxides were
      measured by glutathione peroxidase-catalyzed oxidation of exogenous glutathione.
      With exposure to .OH, cytosolic lipid peroxide levels were increased threefold in
      V-treated hearts, but there was no increase in U74006F-treated hearts. After 30
      min of recovery, developed pressure and maximum first derivative of left
      ventricular pressure were greater in U74006F-treated hearts than in V-treated
      hearts but were still 50 and 44% of levels in saline hearts, respectively.
      Coronary flow was markedly reduced after exposure to free radicals and was only
      slightly less depressed when U74006F was administered. When coronary flow
      following oxidant exposure was increased by nitroglycerin, U74006F again only
      modestly improved systolic function. Thus, although U74006F blocked lipid
      peroxidation, it only slightly improved the ventricular dysfunction caused by
      .OH. Therefore, factors other than lipid peroxidation play a major role in
      oxidant-induced myocardial stunning.

PMID- 7810739
TI  - Endogenous BK stimulates ischemically sensitive abdominal visceral C fiber
      afferents through kinin B2 receptors.
AB  - Abdominal ischemia and reperfusion reflexly activate the cardiovascular system.
      In the present study, we evaluated the role of endogenously produced bradykinin
      (BK) in the stimulation of ischemically sensitive visceral afferents. Single-unit
      activity of abdominal visceral C fiber afferents was recorded from the right
      thoracic sympathetic chain of anesthetized cats during 5 min of abdominal
      ischemia. Abdominal ischemia increased the portal venous plasma BK level from 49
      +/- 10 to 188 +/- 66 pg/ml (P < 0.05). Injection of BK (1 microgram/kg ia) into
      the descending aorta significantly increased impulse activity (0.88 +/- 0.16
      impulses/s) of 10 C fibers, whereas a kinin B1-receptor agonist, des-Arg9-BK (1
      microgram/kg), did not alter the discharge rate. Inhibition of kininase II
      activity with captopril (4 mg/kg i.v.) potentiated impulse activity of 14
      ischemically sensitive C fibers (0.44 +/- 0.09 vs. precaptopril, 0.33 +/- 0.08
      impulses/s; P < 0.05). In addition, a kinin B2-receptor antagonist (NPC-17731; 40
      micrograms/kg i.v.) attenuated activity of afferents during ischemia (0.39 +/-
      0.08 vs. pre-NPC-17731, 0.72 +/- 0.13 impulses/s; P < 0.05) and eliminated the
      response of 10 C fibers to BK. Another kinin B2-receptor antagonist, Hoe-140 (30
      micrograms/kg iv), had similar inhibitory effects on six other ischemically
      sensitive C fibers. In 15 separate cats treated with aspirin (50 mg/kg i.v.), Hoe
      140 (30 micrograms/kg i.v.) attenuated impulse activity of only 3 of 16
      ischemically sensitive C fibers. These data suggest that BK produced during
      abdominal ischemia contributes to the stimulation of ischemically sensitive
      visceral C fiber afferents through kinin B2 receptors.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7810740
TI  - Early disturbance of baroreflex control of heart rate after tail suspension in
      conscious rats.
AB  - Experiments were performed on conscious chronically instrumented rats maintained
      on tail suspension to determine the time course of changes in baroreceptor
      control of heart rate produced by this procedure. Pressor responses were elicited
      by bolus injections of graded doses of phenylephrine and sodium nitroprusside,
      permitting evaluation of the totality of the sigmoidal curve relating mean
      arterial pressure to heart rate. Compared with control rats maintained at 0
      degrees, rats maintained at 20 degrees using tail suspension for 24 h showed a
      significant reduction in reflex gain (-3.9 +/- 0.1 vs. -5.8 +/- 0.3 beats/min; P
      < 0.001) together with a reduction in the upper (472 +/- 11 vs. 512 +/- 5
      beats/min; P < 0.01) and lower (270 +/- 3 vs. 284 +/- 2 beats/min; P < 0.01)
      plateaus of the sigmoidal curve. In three groups of rats, the sigmoidal curve was
      studied successively after returning for 1, 24, and 48 h at 0 degrees. The
      observed change in the gain of the reflex returned toward control values after 48
      h, whereas the other parameters characterizing the sigmoidal curve did not change
      significantly. Transient but significant modifications of heart rate (tachycardic
      response) after the immediate return to the horizontal position were observed.
      The study provides evidence that 1) a significant change of the totality of the
      sigmoidal curve characterizing baroreceptor control of heart rate occurs very
      early after tail suspension in rats and 2) the gain of the reflex is restored
      during the 48 h after release of tail suspension, whereas the other parameters
      characterizing the curve, particularly the plateaus, remain altered.

PMID- 7810741
TI  - Na+/H+ exchange and reperfusion arrhythmias: protection by intracoronary infusion
      of a novel inhibitor.
AB  - Activation of sarcolemmal Na+/H+ exchange has been proposed as a causal factor in
      reperfusion arrhythmogenesis. To test this hypothesis, we determined the
      antiarrhythmic efficacy of two structurally distinct but equipotent Na+H+
      exchange inhibitors, 5-(N-ethyl-N-isopropyl)amiloride (EIPA) and the novel drug,
      3-methylsulfonyl-4-piperidinobenzoyl guanidine (HOE-694), in isolated rat hearts
      (n = 12/group) subjected to independent dual coronary perfusion. After 15 min of
      aerobic perfusion of both beds, flow to the left coronary bed (LCB) was
      terminated for 10 min; this was followed by 5 min of reperfusion. Various
      concentrations of each drug were selectively infused into the LCB either during
      the 5-min period preceding ischemia plus during reperfusion or during reperfusion
      alone. With the former protocol, 0.01, 0.1, 1, and 10 microM EIPA reduced the
      incidence of reperfusion-induced ventricular fibrillation (VF) from 92% in
      controls to 83, 83, 50, and 0% (P < 0.05); the number of hearts in sinus rhythm
      at the end of reperfusion was increased from 17 to 42, 25, 83 (P < 0.05), and
      100% (P < 0.05). HOE-694, at the same concentrations, reduced VF incidence from
      92% in control to 83, 58, 50, and 8% (P < 0.05); 25, 67, 75 (P < 0.05), and 100%
      (P < 0.05) of hearts were in sinus rhythm, compared with 17% of controls, at the
      end of reperfusion. Even when infused during reperfusion alone, both drugs
      afforded significant protection against reperfusion-induced VF, which did not
      differ significantly from that observed when the drugs were also given before
      ischemia. The similar antiarrhythmic efficacy of EIPA and HOE-694 is consistent
      with an arrhythmogenic role for activation of Na+/H+ exchange during early
      reperfusion.

PMID- 7810742
TI  - LPC in oxidized LDL elicits vasocontraction and inhibits endothelium- dependent
      relaxation.
AB  - Oxidized low-density lipoprotein (ox-LDL) plays an important role in the
      development of atherosclerosis and potentially influences the endothelial
      regulation of vasomotor tone. We have recently shown that lysophosphatidylcholine
      (LPC), a lysophospholipid contained in ox-LDL, has various pathophysiological
      effects. We further examined the role of LPC in the ox-LDL-induced vasoactivity
      in isolated pig coronary arteries. Copper-induced ox-LDL but not native LDL (n
      LDL) elicited endothelium-dependent contraction during plateau contraction evoked
      by prostaglandin F2 alpha. Lipid extracted from ox-LDL (ox-LDL-lipid) also
      induced vasocontraction, but lipid of n-LDL (n-LDL-lipid) did not influence tone.
      When LPC was depleted from ox-LDL (i.e., defatted albumin- or phospholipase B
      treated ox-LDL), vasocontraction was significantly attenuated. Synthetic
      palmitoyl LPC also induced endothelium-dependent vasocontraction, mimicking the
      response elicited by ox-LDL, but phosphatidylcholine, which exists in n-LDL and
      is converted to LPC during oxidative modification of LDL, did not influence the
      tone. Contraction to either ox-LDL or LPC was significantly attenuated by NG
      monomethyl-L-arginine but not by indomethacin or superoxide dismutase. Forty
      minutes of incubation of coronary rings with either ox-LDL or LPC significantly
      attenuated endothelium-dependent vasorelaxation to thrombin without affecting
      vasorelaxation to endothelium-independent vasodilator nitroglycerin. In
      conclusion, LPC contained in lipid fraction of ox-LDL caused endothelium
      dependent contraction and inhibited endothelium-dependent relaxation in isolated
      pig coronary arteries. The vasocontraction might be at least in part caused by
      LPC-mediated inhibition of endothelium-derived nitric oxide release.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7810743
TI  - Positive inotropic effect of Streptococcus faecalis in isolated cardiac muscle.
AB  - Infective endocarditis is caused by bacterial colonization of the endocardium.
      Because endocardium modulates mechanical performance of subjacent myocardium, we
      studied acute effects of bacteria on isolated cardiac muscle and on the
      functional role of the endocardium. Bacteria, grown in broth at 37 degrees C,
      were added at increasing concentrations (10(2) to 10(6) bacteria/ml) to cat
      papillary muscles in Krebs-Ringer solution (1.25 mM Ca2+, 35 degrees C). The
      endocardial surface was damaged by exposing muscles to a stream of dry air for 30
      s. Streptococcus (Enterococcus) faecalis induced significant increases in total
      peak isometric twitch tension (TT) and maximal velocity of unloaded shortening
      (Vmax) and significant decreases in time to TT (TtTT) and time to half isometric
      twitch tension decline (RT 1/2), both before and after removal of endocardial
      endothelium. This response could also be elicited with bacterial filtrate, after
      boiling the filtrate or after extracting the polysaccharides from it with KIO4.
      Increasing Ca2+ concentrations progressively reduced the response to the
      filtrate. Propranolol slightly, although not significantly, diminished the
      effects on TT and Vmax while abolishing the effects on TtTT and on RT 1/2. By
      contrast, Streptococcus bovis and Staphylococcus aureus did not affect TT or Vmax
      but induced a slight but significant decrease in TtTT at the highest
      concentration of bacteria. Accordingly, the filtrate of Strep. faecalis induces a
      positive inotropic effect. The active component is neither a protein nor a
      polysaccharide, and its effect may be partly beta-adrenoceptor mediated. Strep.
      bovis and Staph. aureus have negligible acute effects on contractility.

PMID- 7810744
TI  - Adrenergic regulation of coronary microcirculation after extracorporeal
      circulation and crystalloid cardioplegia.
AB  - The purpose of the present study was to examine whether adrenoceptor-mediated
      responses of porcine coronary resistance arteries are affected by cardioplegic
      arrest under conditions of extracorporeal circulation (cardiopulmonary bypass;
      CPB). Pigs were placed on CPB. The hearts were arrested with a cold hyperkalemic
      crystalloid cardioplegic solution for 1 h, then were reperfused for 1 h. In vivo
      and in vitro beta-adrenoceptor-mediated responses were compared before CPB and 2
      min and 1 h after initiation of reperfusion. In vitro responses were studied in a
      pressurized no-flow state with video microscopy. Isoproterenol (0.02
      micrograms.kg-1.min-1, intracoronary) increased coronary blood flow by 100 +/-
      32% (P < 0.001) before CPB and cardioplegic arrest, 17 +/- 7% 2 min
      postcardioplegia (P < 0.01), and 71 +/- 9 (P < 0.001) after 1 h of reperfusion.
      Relaxation of precontracted microvessels (90-180 micron) to isoproterenol, NaF,
      forskolin, and adenosine was reduced after cardioplegic arrest (all P < 0.001).
      After 1 h of postcardiolegia-reperfusion, relaxation responses to forskolin and
      adenosine were completely restored, whereas the responses to isoproterenol (P <
      0.05) and NaF (P < 0.10) were only partially recovered. Cardioplegic arrest and
      postcardioplegia-reperfusion blunted the alpha 2-adrenoceptor-mediated
      endothelium-dependent relaxation to clonidine (P < 0.001) but did not affect the
      minimal (< 4%) contractile response to the alpha 1-adrenoceptor agonist
      phenylephrine or the relaxation to nitroprusside. These results show that
      hyperkalemic cardioplegia results in the generalized defect in the beta
      adrenoceptor-GS protein-adenylate cyclase pathway, which is significantly
      restored after reperfusion.

PMID- 7810746
TI  - Intraretinal oxygen distribution in rats as a function of systemic blood
      pressure.
AB  - Differential responses to induced changes in systemic blood pressure (BP) at
      different layers of both the retinal and choroidal vasculature were observed, by
      monitoring localized PO2 as a function of depth, in the retina and choroid of the
      rat eye using oxygen-sensitive recessed microelectrodes. Visual and
      electrophysiological localization of the microelectrode tip allowed the oxygen
      distribution to be related to the positions of the vascular beds of the retina
      and choroid. Highly reproducible intraretinal PO2 profiles were achieved. The
      relationship between PO2 and systemic BP was linear in the deep capillary layer
      of the retina (PO2 = 0.17 x BP - 2.63) and in the choriocapillaris (PO2 = 0.21 x
      BP + 2.95), whereas it was nonlinear in the superficial retinal capillary layer
      [PO2 = 40.01/[1 + (BP/66.22)-1.22]] and deep choroid [PO2 = 83.82/[1 +
      (BP/124.61)-0.87]]. The minimum PO2 occurred between the two retinal capillary
      beds, and a PO2 gradient was evident in the choroid. The contrasting responses of
      different layers of the two circulations reflect different blood flow control
      mechanisms not evident when studying the circulations as a whole.

PMID- 7810745
TI  - Transition from compensatory hypertrophy to dilated, failing left ventricles in
      Dahl salt-sensitive rats.
AB  - To establish an experimental model for studying a specific transitional stage for
      compensatory hypertrophy to heart failure, we studied the pathophysiology of the
      left ventricle (LV) in Dahl salt-sensitive (DS) rats fed a high-salt diet. DS
      rats fed an 8% NaCl diet after the age of 6 wk developed concentric LV
      hypertrophy at 11 wk, followed by marked LV dilatation at 15-20 wk. During the
      latter stage, the DS rats showed labored respiration with LV global hypokinesis.
      All the DS rats died within 1 wk by massive pulmonary congestion. The dissected
      left ventricles revealed chamber dilatation and a marked increase in mass without
      myocardial necrosis. In contrast, corresponding Dahl salt-resistant (DR) rats fed
      the same diet showed neither mortality nor any of these pathological changes. The
      in vivo LV end-systolic pressure-volume relationship shifted to the right with a
      less steep slope in the failing DS rats compared with that in age-matched DR
      rats. Isometric contractions of LV papillary muscles isolated from these DS rats
      showed reduced tension development in the failing stage, but normal tension
      development in the hypertrophied stage. In conclusion, the DS rat fed a high-salt
      diet is a useful model showing rapidly developing congestive heart failure, in
      which the transition from compensatory hypertrophy to decompensatory dilatation
      of LV is easily and consistently manifested.

PMID- 7810747
TI  - Force-frequency relations during heart failure in pigs.
AB  - In isolated cardiac muscle from patients with severe heart failure (HF) the force
      frequency relation (FFR) is often negative, but the characteristics of the FFR
      under basal conditions and its responsiveness to adrenergic stimulation have not
      been studied in the intact, failing heart. Severe HF was produced in pigs (n = 6)
      by continuous rapid left ventricular (LV) pacing (225 beats/min). In the
      conscious resting state, high-fidelity LV pressure and its maximum first
      derivative (LV dP/dtmax) were obtained over a range of atrial pacing rates (100
      225 beats/min) before (control) and after HF. Before HF, the relationship between
      increased heart rate and LV dP/dtmax (a measure of the FFR) was flat, but during
      dobutamine infusion the FFR showed a significant positive slope (P < 0.003).
      After HF, the basal FFR was depressed, but the slope of the FFR was not increased
      by dobutamine. After HF, responses of dP/dtmax to slowing of HR by a specific
      sinus node inhibitor confirmed the absence of a negative basal FFR. In
      conclusion, the basal LV FFR in conscious pigs with severe HF was not negative.
      Unlike the normal heart, in HF beta-adrenergic receptor stimulation did not
      amplify the FFR, a phenomenon that could play an important role in the impaired
      response to exercise in patients with HF.

PMID- 7810748
TI  - Role of active changes in venous capacity by the carotid baroreflex: analysis
      with a mathematical model.
AB  - To elucidate the role of venous capacity active changes in short-term
      cardiovascular homeostasis, a mathematical model of the carotid-sinus baroreflex
      system has been developed. In the model the cardiovascular system is represented
      as the series arrangement of six lumped compartments, which synthesize the
      fundamental hemodynamic properties of the systemic arterial, systemic venous,
      pulmonary arterial, and pulmonary venous circulations as well as of the left and
      right cardiac volumes. Cardiac outputs from the left and right ventricles are
      computed as a function of both downstream arterial pressure (afterload) and
      upstream atrial pressure (preload). Four distinct feedback regulatory mechanisms,
      working on systemic arterial resistance, heart rate, systemic venous unstressed
      volume, and systemic venous compliance, are assumed to operate on the
      cardiovascular system in response to carotid sinus pressure changes. All model
      parameters, both in the cardiovascular system and in feedback regulatory
      mechanisms, have been assigned on the basis of physiological data now available.
      The model is used here to simulate the pattern of the main hemodynamic quantities
      in the short time period (1-2 min) after acute carotid sinus activation in
      vagotomized subjects. Simulation results indicate that the model can reproduce
      experimental data quite well, with reference both to open-loop experiments and to
      an acute blood hemorrhage performed in closed-loop conditions. Moreover, computer
      simulations indicate that active changes in venous unstressed volume are of
      primary importance in regulating cardiac output and systemic arterial pressure
      during activation of the carotid sinus baroreflex.

PMID- 7810750
TI  - Localization and analysis of natriuretic peptide receptors in the gills of the
      toadfish, Opsanus beta (teleostei).
AB  - The distribution and nature of natriuretic peptide binding sites was determined
      in the gills of the toadfish, Opsanus beta. Specific 125I-labeled rat atrial
      natriuretic peptide (rANP) and 125I-labeled porcine C-type natriuretic peptide
      (pCNP) binding sites were observed on the afferent and efferent filamental
      arteries and lamellar arterioles, and on the marginal channels of the secondary
      lamellae. In both section autoradiography and competition assays, the binding of
      both ligands was completely displaced by 1 microM rANP and 1 microM pCNP, but
      residual binding was observed with 1 microM of the type C natriuretic peptide
      receptor (NPR-C)-specific ligand C-ANF. Electrophoresis of gill membranes cross
      linked with 125I-rANP showed a major band at 75 kDa and a fainter band at 140
      kDa. Both rANP and pCNP significantly stimulated the production of cGMP above
      basal levels; C-ANF had no stimulatory effect. These data show that the
      intrafilamental gill vasculature of toadfish contains a major population of
      natriuretic peptide receptors very similar to mammalian clearance receptors and a
      smaller population of receptors that are linked to a membrane-bound guanylate
      cyclase.

PMID- 7810749
TI  - Tumor necrosis factor-alpha and fever after peripheral inflammation in the rat.
AB  - The involvement of endogenous tumor necrosis factor-alpha (TNF-alpha) in the
      pyrogenic [i.e., rise in colonic temperature (Tc)] and thermogenic [increase in
      oxygen consumption (VO2)] responses to inflammation was investigated in rats
      subjected to an intramuscular injection of turpentine. Turpentine administration
      caused a rise in Tc and VO2 within 2 h (0.9 +/- 0.1 degrees C, 27 +/- 2%,
      respectively). Eighteen to twenty hours after turpentine, the magnitude of these
      responses had increased (2.3 degrees C fever and a 28% increase in metabolic rate
      compared with control animals) and was associated with marked inflammation in the
      injected limb. A rapid (by 4 h) and sustained rise in the plasma concentration of
      the endogenous pyrogen IL-6, but not TNF-alpha, was also observed. Intravenous
      pretreatment with a TNF-alpha antiserum attenuated the rise in Tc observed 2, 8,
      and 18 h after turpentine injection and almost abolished the hypermetabolic
      response observed at 18 h. In addition, the TNF-alpha antiserum inhibited the
      peak rise (8 h) in plasma IL-6 by 76%. These findings indicate that endogenous
      TNF-alpha is involved in fever and hypermetabolism during inflammation and that
      it may exert these effects by inducing the release of IL-6 into circulation.

PMID- 7810751
TI  - The nocturnal increase in human cerebrospinal fluid production is inhibited by a
      beta 1-receptor antagonist.
AB  - A circadian variation in human cerebrospinal fluid (CSF) production has recently
      been demonstrated using magnetic resonance phase imaging. A nightly peak in CSF
      production was found at approximately 0200, when production is approximately
      twice the daytime values. In the present study, we have investigated the effect
      of a beta 1-receptor antagonist, atenolol, on the production of CSF, specifically
      the nocturnal production peak. CSF production was measured in fourteen healthy
      volunteers of both sexes in the time interval 1500-1800, with or without drug
      administration (100 mg orally) at 1800, and a second measurement was made in the
      time interval 2300-0200. In the absence of drug administration, all nine
      volunteers showed a significant increase in CSF production at night, from 0.34 +/
      0.06 ml/min in the time interval 1500-1800 to 0.61 +/- 0.05 (SE) ml/min (P <
      0.005), confirming the presence of a circadian variation in these individuals.
      One week later, the experiment was repeated in five of these volunteers, plus an
      additional five volunteers, but with the administration of 100 mg atenolol orally
      immediately after the first measurement (at 1800). In five of the volunteers a
      decrease in CSF production was seen at midnight compared with daytime production
      values; in two volunteers CSF production remained unchanged, while three
      volunteers showed increased production. The average CSF production was 32% lower
      at night (0.27 +/- 0.10 ml/min) compared with the afternoon (0.40 +/- 0.07
      ml/min), after administration of atenolol (P = 0.37).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7810752
TI  - Plasma volume conservation in pigeons: effects of air temperature during
      dehydration.
AB  - We assessed the effects of the ambient air temperature prevailing during
      dehydration, which included complete water and food deprivation, on plasma volume
      (PV) conservation in pigeons (Columba livia) exposed to air temperatures of 25
      degrees C (n = 7), 36 degrees C (n = 12), and 40 degrees C (n = 24). The pigeons
      were dehydrated for 65.4, 32.3, and 27.7 h, on average, at 25, 36, and 40 degrees
      C, respectively. Dehydration rates averaged 5, 10, and 15.2% of initial total
      body water (TBW) per day at the three air temperatures, in ascending order. Birds
      exposed to 25 and 36 degrees C maintained PV despite the fact that they lost, on
      average, 14 and 17.3% of their TBW, respectively. In contrast, PV in pigeons
      exposed to 40 degrees C decreased by 8.9%, even though the reduction in TBW
      (17.7%) was similar to that incurred at 36 degrees C. Mean plasma osmolalities
      reached 347.7, 345.6, and 374.8 mosmol/kgH2O at 25, 36, and 40 degrees C,
      respectively. No significant changes occurred in hematocrit (Hct) and hemoglobin
      concentrations (Hb) during dehydration at 25 and 36 degrees C. However, at 40
      degrees C Hb increased by 8.2% with no change in Hct, indicating a decrease in
      red blood cell volume (RBCV). The results of this study suggest that maintenance
      of PV and RBCV is affected not only by the dehydration level attained but also by
      the ambient conditions under which dehydration is induced and the rate at which
      dehydration takes place.

PMID- 7810753
TI  - Circadian and ultradian rhythms of peripheral prolactin concentrations in
      lactating dairy cows.
AB  - To investigate possible circadian and ultradian periodicities for peripheral
      prolactin in lactating dairy cows, integrated 15-min blood samples taken
      sequentially over 48 h from six cows were analyzed by radioimmunoassay. Cows were
      housed in an environmental chamber at 19 degrees C with lights on 0700 to 2300,
      fed daily at 0900, and milked at 0800 and 2000. Peripheral concentrations
      exhibited sinusoidal circadian rhythms. For two cows, a nadir of 15 ng/ml
      occurred around 1900 and a zenith of 29 ng/ml around 0730. For four cows,
      circadian rhythms were 180 degrees out of phase, with a nadir of 28 ng/ml around
      0840 and a zenith of 40 mg/ml around 1920. Ultradian peaks, which varied in
      amplitude within and among animals, showed no consistent relationship with either
      milking or feeding. Spectral analyses indicated rhythms around 100 min for the
      first two animals and 150 min for the four animals. In conclusion, there were no
      simple relations between prolactin rhythms and lights on or lights off. Further,
      results suggest that changes in the phase of circadian rhythms may be associated
      with changes in the periods of ultradian rhythms.

PMID- 7810754
TI  - Chronic and selective vasopressin blockade in spontaneously hypertensive rats.
AB  - Chronic effects of orally available, nonpeptide vasopressin V1 and V2 receptor
      antagonists on conscious spontaneously hypertensive rats (SHR) were investigated.
      SHR and Wistar rats were divided into four groups, groups S-1 to S-4 and W-1 to W
      4, respectively. Groups S-1 and W-1 were untreated as control. Groups S-2 and W-2
      were treated with V1 antagonist, groups S-3 and W-3 received V2 antagonist, and
      groups S-4 and W-4 were treated with both of V1 and V2 antagonists. V1 and/or V2
      antagonists did not affect degree of blood pressure of W-2, W-3, and W-4 rats,
      and V1 antagonist, alone or combined with V2 antagonist, slightly reduced
      increases in blood pressure of S-2 and S-4 rats without significance. However, V2
      antagonist induced significantly massive and hyposmolar urine in W-3 rats
      compared with that in S-3 rats. In conclusion, in SHR, circulating vasopressin
      contributes to increases in blood pressure via either V1 or V2 receptors less
      than expected from previous studies with antibodies or peptide antagonists.

PMID- 7810756
TI  - Fetal hiccups in the baboon.
AB  - Bouts of hiccuping are recognized by pregnant women as distinct episodic
      movements of their fetuses. Ultrasound imaging of these fetuses has documented
      the occurrence of hiccups from early gestation through parturition. This study
      provides a systematic characterization of prenatal hiccuping in the fetal baboon
      (Papio species). Tracheal fluid pressure was recorded from 11 chronically
      instrumented fetal baboons for 21.5 +/- 7.3 consecutive days (mean +/- SD) over a
      range in gestation from 124 to 164 days (term 175 days). In an initial review of
      pressure recordings by visual inspection, hiccups were recognized as distinctive
      high-amplitude fluctuations in tracheal pressure that were readily discriminated
      from fetal breaths. Automated techniques were then developed and validated to
      detect hiccups and summarize their features. The mean hiccup amplitude was 23.0
      +/- 3.1 mmHg, inspiratory time was 0.26 +/- 0.03 s, and expiratory time was 0.27
      +/- 0.02 s. Each of these features discriminated hiccups from breaths (P <
      0.001). Hiccuping incidence (1.8 +/- 0.4% of time), rate (26.2 +/- 6.2 min-1),
      bout duration (4.3 +/- 0.8 min), and the interval between bouts (3.35 +/- 0.60 h)
      were also different (P < 0.01) from breathing. These features of hiccups remained
      relatively constant over the latter third of gestation with the exception of an
      increase in duration of the expiratory time interval (r = 0.54, P < 0.01).
      Despite their vigorous nature, bouts of hiccuping were not associated with
      transitions in behavioral state. Moreover, the features of hiccups were not
      differentiated by state. Bouts of hiccuping recurred in a cyclic fashion, on
      average every 3-4 h.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7810755
TI  - Interaction between angiotensin II and nitric oxide in control of renal
      hemodynamics in conscious dogs.
AB  - Recent in vitro studies have provided evidence that the vasoconstrictor actions
      of angiotensin II on afferent arterioles are enhanced by nitric oxide synthesis
      inhibition. Although these studies suggest that nitric oxide may play a role in
      protecting the afferent arterioles from angiotensin II-induced vasoconstriction,
      the importance of this interaction in the regulation of glomerular filtration
      rate and renal blood flow in the intact, conscious animal is not known. The
      objective of the present study was to determine the role of nitric oxide in
      modulating the renal hemodynamic and excretory effects of angiotensin II.
      Angiotensin II was infused at rates of 0.5, 1.0, and 2.0 micrograms.kg-1.min-1
      intrarenally in conscious, chronically instrumented dogs in both the presence and
      absence of nitric oxide synthesis inhibition by continuous intrarenal infusion of
      NG-nitro-L-arginine methyl ester (3 micrograms.kg-1.min-1). At a dose of 0.5
      micrograms.kg-1.min-1, angiotensin II decreased renal plasma flow by 19%, while
      having no effect on glomerular filtration rate in control dogs. In contrast,
      angiotensin II decreased renal plasma flow by 54%, glomerular filtration rate by
      40%, and increased renal vascular resistance by 125% in the presence of
      intrarenal nitric oxide synthesis blockade. At doses of 1.0 and 2.0 micrograms.kg
      1.min-1, angiotensin II reduced renal plasma flow by 36 and 45%, glomerular
      filtration rate by 17 and 23%, and increased renal vascular resistance by 80 and
      120%, respectively, in control dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7810758
TI  - Cholecystokinin reduces sucrose palatability in rats: evidence in support of a
      satiety effect.
AB  - To investigate the hypothesis that peripherally administered cholecystokinin
      (CCK) reduces food intake by the production of aversive internal cues, we
      examined the effects of the sulfated, octapeptide form of CCK on taste reactivity
      responses to oral sucrose infusions in male rats implanted with intraoral
      cannulas. After injection of CCK (4, 8, or 16 micrograms/kg ip) or 0.15 M saline
      (1 ml/kg ip), a series of brief (30 s) intraoral infusions of a 0.30 M sucrose
      solution was administered at 2-min intervals for 10 min. All doses of CCK were
      found to significantly decrease ingestive responding during the first and
      subsequent sucrose infusions without promoting a significant increase in aversive
      responses relative to controls. The lack of a gradual, conditioned shift in taste
      reactivity responses, from an ingestive to an aversive pattern (which is
      typically observed after LiCl administration), suggests that the production of
      nausea-like aversive internal cues was likely not responsible for the observed
      CCK-induced alterations in taste reactivity responses. It appears that the
      unconditioned, satiogenic effects of CCK contributed to the selective reduction
      in ingestive responses observed in the present study.

PMID- 7810757
TI  - GLUT3 glucose transporter isoform in rat testis: localization, effect of diabetes
      mellitus, and comparison to human testis.
AB  - Facilitative hexose transporter expression was compared in rat and human testes.
      In rat testis, only GLUT1 and GLUT3 proteins were expressed. By contrast, human
      testis expressed GLUT1 and GLUT3 in addition to GLUT5. Immunocytochemical studies
      showed that GLUT3 was expressed in all cells of the seminiferous epithelium of
      rat testis, including sperm. In human testis, GLUT3 was expressed exclusively in
      cells juxtaposed to the lumen of the seminiferous tubule and ejaculate sperm, a
      pattern of expression that was identical to that of GLUT5. Induction of
      insulinopenic diabetes mellitus in the rat did not alter the levels or the
      distribution of GLUT3 protein or mRNA in the testis. Moreover insulin treatment
      of the diabetic rats did not produce changes in GLUT3 mRNA or protein levels. The
      results show that rat and human testis express the high-affinity glucose
      transporter GLUT3, which allows for the efficient uptake of glucose. In addition,
      the testis may be protected from changes in glucose transporter expression in
      experimental diabetes.

PMID- 7810760
TI  - Ventilatory and metabolic responses to hypoxia in the echidna, Tachyglossus
      aculeatus.
AB  - Oxygen consumption (VO2), CO2 production (VCO2), and minute ventilation (VE)
      together with breathing pattern were measured in echidnas during normoxia and
      hypoxia. In normoxia, VO2, VCO2, and VE were all found to be approximately 30% of
      the allometric prediction for a eutherian. As a consequence VE/VO2 and VE/VCO2
      are as predicted for a mammal. This is in contrast to previous reports on the
      echidna in which the VE was shown to be low and the echidna, subsequently, to be
      in a state of hypoventilation. It is possible that the difference between this
      and previous studies is related to the resting state of the echidna; echidnas in
      this study adopted a curled-up "sleeping" posture, and measurements were made
      without tactile disturbance. Breathing pattern was typical of a semifossorial
      species in that inspiration time to total breath time was short when compared
      with the normal eutherian value. In graded hypoxia VE increased [threshold
      fractional concentration of inspired O2 (FIO2) = 0.125], predominantly the result
      of changes in frequency achieved through a shortening in expiration time. In
      acute hypoxia (FIO2 = 0.10) VE/metabolic rate showed a tendency to increase,
      mainly because of the increase in VE. Approximately 50% of the increase in VE
      could be attributed to the 25% increase in VO2 and VCO2 that occurred in acute
      hypoxia. Given that the general mammalian response to hypoxia is a drop in
      metabolic rate, possible reasons as to why the echidna does not decrease
      metabolic rate in hypoxia are discussed.

PMID- 7810759
TI  - Insulin resistance and hypertension: studies in transgenic hypertensive TGR(mREN
      2)27 rats.
AB  - The link between hyperinsulinemia and hypertension is imperfectly understood.
      Recently, a renin gene (the mouse DBA/REN-2d gene) has been transfected into
      rats, leading to high blood pressure in transgene-positive animals, TGR(mREN-2)27
      rats. We tested whether heterozygous hypertensive TGR(mREN-2)27 rats presented
      evidence of insulin resistance in comparison with the parent strain of Sprague
      Dawley rats. Despite their higher blood pressure (203 +/- 8 vs. 112 +/- 6 mmHg, P
      < 0.001), transgenic rats had normal fasting levels of plasma glucose, insulin,
      free fatty acids, and triglycerides and had normal fasting rates of hepatic
      glucose production (by [14C]glucose infusion). During a euglycemic
      hyperinsulinemic clamp (3 mU/min), stimulation of whole body glucose utilization
      was equivalent in transgenic and control animals (12.6 +/- 0.6 vs. 10.9 +/- 1.0
      mg.min-1.kg-1, respectively). Likewise, suppression of hepatic glucose output by
      insulin was complete in both groups. The glucose utilization index (as measured
      by the 2-deoxy-D-[3H]glucose technique) was similar between transgenic and
      control animals in several skeletal muscles (soleus, extensor digitorum longus,
      tibialis, diaphragm, white and red quadriceps, and white and red gastrocnemius),
      in white adipose tissue (periovarian and inguinal), and in brown adipose tissue.
      We conclude that single gene hypertension does not alter whole body and
      individual tissue insulin sensitivity.

PMID- 7810761
TI  - Hydrops fetalis in nephrectomized fetal lambs infused with angiotensin I.
AB  - Nine bilaterally nephrectomized fetal sheep were infused for 6 days with
      angiotensin I in sterile water, and five nephrectomized fetal sheep were infused
      for 6 days with water alone. Total dose of angiotensin was 13.8 +/- 8.6 (SD)
      mg/kg fetal dry wt, and the total volumes of infused water were 303 +/- 201 and
      423 +/- 164 ml, respectively. Of the fetuses infused with angiotensin I, one was
      of normal appearance, two showed moderate hydrops fetalis, and the remaining
      fetuses were grossly hydropic. All water-infused fetuses were normal. Their wet
      to-dry weight ratios were 7.98 and 6.36 (P < 0.015), representing a 25% of normal
      body weight excess of water in the angiotensin I-infused fetuses. Six days of
      angiotensin I infusion caused a gradual rise in fetal arterial blood pressure
      from 37 +/- 15 to 81 +/- 15 mmHg (P < 0.05) and a gradual rise in venous blood
      pressure from 2.7 +/- 1.0 to 10.5 +/- 1.7 mmHg (P < 0.05). It was concluded that
      the fetal edema was due to the elevation in venous pressure. Plasma
      concentrations of Na+, K+, Cl-, HCO3-, total alpha-amino acids, fructose,
      glucose, and lactate in the fetus and the ewe did not identify an osmotically
      active solute responsible for the transplacental attraction of excess water into
      the conceptus, and the mechanism that attracted this excess water across the
      placenta remains unclear.

PMID- 7810762
TI  - Blood and brain temperatures of free-ranging black wildebeest in their natural
      environment.
AB  - Using miniature data loggers, we measured the temperatures of carotid blood and
      brain in four wildebeest (Connochaetes gnou) every 2 min for 3 wk and every 5
      min, in two of the animals, for a further 6 wk. The animals ranged freely in
      their natural habitat, in which there was no shelter. They were subject to
      intense radiant heat (maximum approximately 1,000 W/m2) during the day. Arterial
      blood temperature showed a circadian rhythm with low amplitude (< 1 degree C) and
      peaked in early evening. Brain temperature was usually within 0.2 degrees C of
      arterial blood temperature. Above a threshold between 38.8 and 39.2 degrees C,
      brain temperature tended to plateau so that the animals exhibited selective brain
      cooling. However, selective brain cooling sometimes was absent even when blood
      temperature was high and present when it was low. During helicopter chases,
      selective brain cooling was absent, even though brain temperature was near 42
      degrees C. We believe that selective brain cooling is controlled by brain
      temperature but is modulated by sympathetic nervous system status. In particular,
      selective brain cooling may be abolished by high sympathetic activity even at
      high brain temperatures.

PMID- 7810763
TI  - Effects of glucose and fructose solutions on food intake and gastric emptying in
      nonobese women.
AB  - The differential effects of fructose and glucose on food intake were studied by
      giving two concentrations (1 and 10%) of glucose and fructose solutions (500 ml)
      to one group of women 30 min, and to another 135 min, before a meal of macaroni
      and beef. The 1% solutions of each sugar were sweetened to match 10% fructose by
      selective additions of aspartame. Gastric emptying of the 10% solutions and water
      was measured for 90 min. Under the 30-min delay, subjects ate a mean of 75.8 g
      more (P < 0.05) after the 1% solutions than after water, and 52.2 g (P > 0.05)
      less after the 10% solutions than after water, but there were no differences in
      intake between types of sugar under either delay nor between concentrations at
      the 135-min delay. However, 10% fructose and 1% glucose sweetened to match it
      reduced intake significantly compared with water. Glucose (10%) emptied
      significantly slower (t1/2 = 93.61 min) than water (t1/2 = 29.77 min), while
      fructose (10%) was intermediate (t1/2 = 65.45 min). Therefore, gastric emptying
      differences did not account for these results. We conclude that sweetener
      enhanced dilute sugar solutions may increase subsequent intake at 30 min, but
      dilute glucose solutions may have potential for substantial energy savings if
      consumed 135 min before a meal.

PMID- 7810764
TI  - Nifedipine inhibits adrenal but not circulating catecholamine response to
      nicotinic stimulation in dogs.
AB  - We investigated whether dihydropyridine-sensitive L-type Ca2+ channels are
      implicated in adrenal and sympathetic neural catecholamine release in response to
      nicotinic stimulation by 1,1-dimethyl-4-phenylpiperazinium (DMPP), a selective
      cholinergic nicotinic agonist, in dogs anesthetized with pentobarbital sodium.
      Plasma epinephrine and norepinephrine concentrations were measured in adrenal
      venous and aortic blood by a high-performance liquid chromatography
      electrochemical method. In the vehicle control group, intravenous injection of
      DMPP (15 micrograms/kg iv) produced a significant increase in adrenal venous
      catecholamine output and aortic catecholamine concentration. These increasing
      responses were highly reproducible on the repetition of DMPP injection given 30
      min after the first injection. In dogs receiving nifedipine (100 micrograms/kg
      iv), the net increase in adrenal venous epinephrine and norepinephrine output in
      response to DMPP was attenuated by 42% (P < 0.05), while no significant changes
      were observed in the aortic catecholamine response to DMPP. In dogs treated with
      pentolinium (1 mg/kg iv), both adrenal epinephrine and norepinephrine responses
      to DMPP were inhibited by 67% (P < 0.05) and 84% (P < 0.05), respectively.
      Furthermore, pentolinium inhibited aortic catecholamine response to DMPP by > 95%
      (P < 0.05). The present study suggests that DMPP-induced release of adrenal
      catecholamines was mediated, at least in part, through mechanisms involving
      dihydropyridine-sensitive L-type Ca2+ channels under in vivo conditions. By
      contrast, however, the results also suggest that dihydropyridine-sensitive L-type
      Ca2+ channels were not implicated in the neurotransmission at the level of
      sympathetic ganglions.

PMID- 7810765
TI  - Muscarinic inhibition of cardiac norepinephrine and neuropeptide Y release during
      ischemia and reperfusion.
AB  - It was the aim of the present study to characterize the modulatory effect of
      muscarinic agonists on the overflow of norepinephrine and neuropeptide Y (NPY)
      from the in situ perfused guinea pig heart, induced by electrical stimulation of
      the left stellate ganglion (6 Hz, 5 V, 1 min). The muscarinic agonists
      oxotremorine (0.01-1 microM) and carbachol (0.1-10 microM) reduced norepinephrine
      and NPY overflow in a concentration-dependent manner to approximately 30% of
      control. The inhibitory effect of carbachol was antagonized by the unspecific
      muscarinic antagonist atropine (1 microM) but not by the nicotinic antagonist
      hexamethonium (100 microM). The M2-specific antagonist AF-DX-116BS was 25 times
      more potent than the M1-specific antagonist pirenzepine in antagonizing the
      inhibitory effect of carbachol [50% inhibitory concentration (IC50) = 0.2 microM
      for AF-DX-116BS; IC50 = 5.0 microM for pirenzepine]. These findings indicate that
      presynaptic muscarinic inhibition of stimulated norepinephrine and NPY release
      from the guinea pig heart is mediated mainly by activation of M2 receptors. As
      early as 2 min after stop-flow ischemia, the inhibitory effect of carbachol (10
      microM) on the stimulation-evoked overflow of norepinephrine and NPY was lost. On
      reperfusion with oxygenated buffer after 10 min of stop-flow ischemia the
      inhibitory effect of carbachol (10 microM) on stimulation-induced norepinephrine
      and NPY overflow recovered within 3 min.

PMID- 7810766
TI  - Stress-induced norepinephrine release in the rat prefrontal cortex measured by
      microdialysis.
AB  - Norepinephrine (NE) release in the medial prefrontal cortex (PFC) of rats was
      studied during immobilization using an intracerebral microdialysis technique. A
      series of experiments using pharmacological and physiological manipulations
      indicated that the NE recovered in the medial PFC dialysate was mainly derived
      from nerve terminals and that the dorsal noradrenergic bundle was a major source
      of NE in the medial PFC. Immobilization stress immediately elevated NE levels to
      176.0 +/- 9.0% of basal release, and this increase continued for the entire
      period of stress and 20 min after termination of the stress. Preinjection of a
      benzodiazepine receptor agonist, diazepam (5 mg/kg ip), significantly attenuated
      immobilization-induced NE release, while injection of an anxiogenic compound, FG
      7142 (20 mg/kg ip), facilitated NE release in an obviously nonstressed condition.
      These results therefore suggest that stressful stimuli activate the NE system in
      the medial PFC, which may be modulated by an activation of benzodiazepine
      receptors in the brain.

PMID- 7810767
TI  - Seasonal and temperature-induced changes in myosin heavy chain composition of
      crucian carp hearts.
AB  - Myosin heavy chain isoforms of the ventricular myocardium from crucian carp
      (Carassius carassius L.) hearts were analyzed in different times of the year by
      gradient sodium dodecyl sulfate-polyacrylamide gel electrophoresis [K. A. Esser,
      M. O. Boluyt, and T. P. White, Am. J. Physiol. 255 (Heart Circ. Physiol. 24):
      H659-H663, 1988]. In winter only one myosin heavy chain type was present, but in
      summer about one-half of the winter myosin was replaced by more slowly moving
      summer myosin. The occurrence of summer myosin correlated with seasonal changes
      in water temperature of the pond, where the fish were caught. Furthermore, the
      heavy chain composition of the heart was altered by temperature acclimation in
      the laboratory: cold-acclimated (2 degrees C) fish had only winter myosin, but
      warm-acclimated (22 degrees C) fish had both summer and winter myosin in about
      equal amounts. Myosin adenosinetriphosphatase activity of the hearts containing
      both summer and winter myosin was higher than that of hearts containing only
      winter myosin. Functionally, changes in myosin heavy chain composition were
      associated with inverse thermal acclimation in the heart rate. Warm-acclimated
      fish had higher in vitro heart rate and shorter contraction duration than cold
      acclimated animals. Present findings suggest that changes in myosin heavy chain
      composition together with concomitant changes in Ca2+ activation of contraction
      make possible large seasonal alterations in the activity of crucian carp hearts.
      These adjustments are needed to adapt the cardiovascular system to winter
      hibernation and summer activity, which are dictated by seasonally bound changes
      in environmental conditions.

PMID- 7810768
TI  - Validation of the doubly labeled water method in growing pigs.
AB  - The CO2 production (rCO2) of eight growing pigs was determined by continuous
      collection of CO2 over 21 days and simultaneously estimated using the doubly
      labeled water (DLW) method. The aim was to assess the accuracy of the method
      before and after correction for known sources of error and to test for any
      residual discrepancy arising from as yet unidentified sources of error. Mass
      spectrometer accuracy was verified by analyzing serial dilutions of the dose
      material in the form of an artificial decay curve; no significant bias was
      detected. The physiological errors were linearly dependent on weight gain. DLW
      derived rCO2 (corrected only for fractionated water loss) underestimated the true
      value by 0.270 l CO2/g wt gain or -8% in the restricted (group R) and -16% in the
      ad libitum-fed (group AL) groups. Known sources of error accounted for -0.006
      (methane), -0.032 (fecal 2H losses), -0.108 (fat synthesis), and -0.146 (changing
      pool size) l CO2/g wt gain. After correction for these sources of error the DLW
      derived rCO2 differed from the true value by -2 +/- 3% in group R and 0 +/- 3% in
      group AL. Thus there was no significant bias in the DLW method after correction
      for known sources of error, even during rapid weight gain or at weight stability
      with or without correction. The precision estimates include both dose and
      background errors and uncertainty in the correction factors used. Strategies for
      optimizing precision are presented.

PMID- 7810769
TI  - Does the histaminergic system mediate bombesin/GRP-induced suppression of food
      intake?
AB  - Bombesin (BN) and its mammalian homologue, gastrin-releasing peptide (GRP), are
      potent satiety agents and have been implicated in the physiological regulation of
      food intake. The mechanism(s) of action of this effect remains unclear. There is
      a functional and anatomic overlap between histamine and BN in relationship to
      feeding, which led us to hypothesize that BN may mediate its satiety effects
      through activation of the histaminergic system. To assess this contention, we
      examined the effects of R-alpha-methylhistamine (alpha-MH) and Imetit, selective
      H3-receptor agonists that inhibit the release and synthesis of histamine, on BN-
      or cholecystokinin (CCK)-induced satiety. In this report we present the first
      evidence for the role of histamine H3 receptors in the mediation of BN-elicited
      satiety. During the first hour of the 4-h daily feeding session, BN reduced food
      intake by > 50% relative to the control condition; this suppression was blocked
      by prior treatment with the H3-receptor agonist, alpha-MH. This blockade of BN
      induced satiety was dose related and selective to BN as alpha-MH failed to
      attenuate sulfated CCK-8-induced satiety. When alpha-MH was administered alone,
      it failed to significantly affect food intake. The specificity of this effect was
      further supported by the demonstration that another H3 agonist, Imetit, was also
      able to block the feeding-suppressant effects of BN. Furthermore, thioperamide,
      an H3-receptor antagonist, blocked these effects of Imetit.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7810770
TI  - Comparison of acute phase responses induced in rabbits by lipopolysaccharide and
      double-stranded RNA.
AB  - Infection of injury results in several systemic and central reactions termed the
      acute phase response (APR). Substantial evidence suggests that cytokines induced
      by microbes initiate the APR. We compared the APR induced in rabbits by a model
      bacterial stimulus, lipopolysaccharide (LPS), to that induced by a model viral
      stimulus, polyriboinosinic:polyribocytidylic acid (poly I:C). The cytokine mRNA
      responses in a mouse macrophage cell line (RAW 264.7) to LPS or poly I:C were
      also determined. Rabbits were injected intravenously or intracerebroventricularly
      with different doses of LPS or poly I:C. Colonic temperatures (Tco) and blood
      samples were taken at the time of injection and at 3, 6, and 24 h after
      injection. Leukocyte numbers, serum antiviral activity, serum ceruloplasmin, and
      plasma fibrinogen were analyzed. Both intravenously injected LPS and poly I:C
      increased Tco, decreased leukocytes, and increased ceruloplasmin. Only LPS by the
      intravenous route increased fibrinogen, whereas only intravenously injected poly
      I:C induced antiviral activity. Intracerebroventricular injections of LPS and
      poly I:C also elicited dose-dependent febrile responses but did not change the
      hematologic APR significantly except for fibrinogen. The primary distinctions
      between LPS and poly I:C with respect to cytokine induction in the RAW 264.7
      macrophage cell line were that LPS failed to induce interferon (IFN)-alpha, poly
      I:C induced interleukin (IL)-6 mRNA minimally and for a shorter time period than
      did LPS, and LPS induced IL-1 alpha and IFN-beta more rapidly than did poly
      I:C.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7810771
TI  - Insulin and Na-dependent alanine transport in skeletal muscle of obese Zucker
      (fa/fa) rats.
AB  - Obese Zucker (fa/fa) rat skeletal muscle is characterized by a reduced rate of
      muscle protein deposition possibly due to alterations in amino acid transport.
      The purpose of the present study was to investigate alanine transport in plasma
      membrane vesicles from skeletal muscle of lean and obese Zucker rats,
      facilitating the study of alanine transport independent of cellular metabolism.
      Initial rates of alanine transport were measured in the presence and absence of
      Na using a rapid filtration technique, and the properties of membranes from
      control and maximally insulin-treated lean and obese Zucker rats were studied.
      For lean rats, the maximal stimulation (Vmax) for Na-dependent alanine transport
      was 207 pmol.mg-1.s-1, and the half-maximal affinity constant (K1/2) was 2.3 mM.
      Insulin treatment increased the Vmax to 387 pmol.mg-1.s-1 with no changes in
      K1/2. For the obese rats, the Vmax for Na-dependent alanine transport was 248
      pmol.mg-1.s-1, and the K1/2 was 2.8 mM. These values were not changed by insulin
      treatment. Thus Na-dependent alanine transport in obese rat skeletal muscle is
      resistant to stimulation by insulin; this alteration may contribute to the
      abnormal muscle protein metabolism observed in these animals.

PMID- 7810772
TI  - Pregnant rats are refractory to the natriuretic actions of atrial natriuretic
      peptide.
AB  - Normal pregnant women and rats undergo a volume expansion. Atrial natriuretic
      peptide (ANP) is involved in volume homeostasis and is stimulated in response to
      volume expansion in nonpregnant animals, resulting in natriuresis and diuresis.
      The conscious, chronically catheterized rat was used to measure mean arterial
      blood pressure (MABP) and renal responses to administered ANP (160 ng.kg-1.min-1
      i.v.) to determine if the actions of ANP are altered by pregnancy. These
      experiments examined virgin (n = 7) and pregnant rats, studied on gestational
      days 7-9 (n = 9) and 15-17 (n = 7). Renal clearance studies (with inulin and p
      aminohippurate) were conducted in control conditions and during 60 min of ANP
      infusion. After the ANP infusion, plasma ANP concentrations were measured in
      virgin and pregnant rats. MABP fell with ANP infusion to similar absolute values
      in virgins (112 +/- 2 to 80 +/- 6 mmHg), 7- to 9-day pregnant (114 +/- 2 to 91 +/
      3 mmHg), and 15- to 17-day pregnant (107 +/- 2 to 88 +/- 4 mmHg) rats although
      the percent decline in MABP in 15- to 17-day pregnant rats was less than in
      virgins. Plasma ANP concentrations were similar in all groups. ANP had no effect
      on glomerular filtration rate, renal plasma flow, or renal vascular resistance in
      virgin or pregnant rats. ANP increased sodium excretion in virgins and in 7- to 9
      day pregnant rats (+102 +/- 27 and +135 +/- 47%, respectively) but not in 15- to
      17-day pregnant animals (+23 +/- 22%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7810773
TI  - Pathogenesis of hyponatremia in an experimental model of the syndrome of
      inappropriate antidiuresis.
AB  - Rats were infused with a selective agonist of vasopressin V2 receptors (1
      desamino-D-arginine vasopressin; DDAVP) at two different doses (1 or 5 ng/h) and
      fed a liquid formula to produce both moderate (plasma [Na+] = 119-124 mmol/l) and
      severe (plasma [Na+] = 106-112 mmol/l) hyponatremia. Whole body water and
      electrolyte contents were analyzed after 1, 7, and 14 days of hyponatremia to
      assess the relative contributions from water retention and sodium depletion to
      hyponatremia of varying duration and severity. Body water of the hyponatremic
      rats was significantly increased over normonatremic control rats after 1 and 7
      days; after 14 days, the 1 ng/h DDAVP-infused rats also had elevated body water,
      but the 5 ng/h DDAVP-infused rats returned to levels not significantly different
      from controls. Body Na+ and Cl- both decreased significantly after 1 day of
      hyponatremia, and these decreases were sustained for 14 days; measured decreases
      were significantly greater in the more hyponatremic rats compared with the less
      hyponatremic rats. Body K+ of the 1 ng/h DDAVP-infused rats was not different
      from control rats, but significant K+ decreases occurred in the 5 ng/h DDAVP
      infused rats after 7 and 14 days. Analysis of the measured plasma Na+
      concentrations vs. those predicted by the changes in body water and sodium showed
      that both water retention and sodium losses were necessary to predict the final
      plasma [Na+]. However, the relative contribution from each varied with the
      duration of induced hyponatremia: acutely, water retention was the major cause of
      decreased plasma [Na+], but sodium depletion became predominant with longer
      periods of sustained hyponatremia.

PMID- 7810774
TI  - Stimulation of oxytocin release within the supraoptic nucleus and into blood by
      CCK-8.
AB  - Simultaneous microdialysis in brain and blood was used to monitor the effects of
      systemic and central cholecystokinin octapeptide (CCK-8) on the release of
      oxytocin and vasopressin within the hypothalamic supraoptic nucleus (SON) as well
      as into blood of urethan-anesthetized female rats. Administration of CCK-8 (20
      micrograms/kg iv) increased oxytocin contents in 30-min microdialysates sampled
      simultaneously within the SON (1.8-fold) and blood (2.4-fold, both P < 0.05)
      compared with prestimulation levels. In another experiment, after bilateral
      administration of CCK-8 directly into the SON (10 ng/0.5 microliter) via a
      microdialysis/infusion probe, oxytocin contents in dialysates sampled from the
      left and right SON were increased 2.3- and 1.7-fold (P < 0.05), respectively. In
      simultaneously sampled dialysates from the jugular vein, oxytocin content
      increased 2.3-fold (P < 0.05). In contrast, oxytocin in dialysates sampled
      outside the hypothalamic nuclei was not altered by systemic or central CCK-8. The
      direct infusion of CCK-8 into both SON increased the release of vasopressin
      within the SON 1.7-fold (P < 0.05) but failed to significantly change vasopressin
      release into blood. The present findings show a coordinated regulation of
      intranuclear and systemic release of oxytocin in response to systemic and central
      CCK-8 and provide further evidence for a possible involvement of endogenous
      oxytocin in the complex regulation of ingestive and reproductive behaviors
      induced by CCK-8 at the brain level.

PMID- 7810775
TI  - Dissociation between vasopressin and oxytocin mRNA and peptide secretion after
      AV3V lesions.
AB  - The effect of hypertonic NaCl consumption on vasopressin (VP) and oxytocin (OT)
      mRNA levels and plasma and pituitary peptides was evaluated in rats with sham or
      anterior ventral third ventricular (AV3V) lesions. Rats were given tap water or
      2% NaCl for 4 days. Because the rats with lesions drank significantly less salt
      solution than the controls (78.8 +/- 17.4 vs. 205.5 +/- 37.8 ml/4 days), a second
      control group was included in which saline intake was matched to the lesioned
      group. AV3V rats showed a deficit in the peptide response to the osmotic
      stimulus. There was no increase in plasma VP or OT or decrease in posterior
      pituitary peptide content in the face of an extreme hypernatremia: plasma sodium
      of 180.1 +/- 4.2 meq/l. Evaluation of mRNA changes by means of in situ
      hybridization showed that animals with lesions responded to the salt challenge
      with increases in hypothalamic VP and OT mRNA levels. There were significant
      increases in paraventricular and supraoptic OT mRNA and paraventricular VP mRNA
      in the lesioned group. The salt-matched control group showed no changes in
      peptide mRNA levels. These results demonstrate that AV3V lesions produce an
      impairment of the salt-neuroendocrine reflex but a persistence of the peptide
      mRNA response. Differences in control mechanisms must account for this
      dissociation between peptide mRNA expression and peptide secretion.

PMID- 7810776
TI  - Temperature gradient osmometer and anomalies in freezing temperatures.
AB  - We have developed a new device that measures freezing and melting temperatures in
      nanoliter volume samples and can be used as a "freezing point osmometer" with a
      resolution many orders of magnitude greater than that of existing freezing point
      osmometers. Using this device we found anomalies in the depression of the
      freezing temperature and thermal hysteresis in aqueous solutions of hydrophilic
      amino acids, polyamino acids, and lectins. These anomalies would not have been
      possible to detect with currently used technology. The compounds that produce
      anomalies in freezing temperature were reported in the literature as having the
      ability to bind to cell membranes. This suggests a relation between a molecule's
      ability to bind to cell membranes and its anomalous freezing temperature
      depression. The new freezing point osmometer and our results could be important
      for studying and understanding organic molecules and their interaction with
      membranes and water.

PMID- 7810777
TI  - CNP is present in canine renal tubular cells and secreted by cultured opossum
      kidney cells.
AB  - C-type natriuretic peptide (CNP) is a vasoactive and antimitogenic peptide that
      is structurally similar but genetically distinct from atrial natriuretic peptide.
      While first discovered in the brain, CNP has been shown to be produced by
      endothelial cells and may function in a paracrine and autocrine fashion in the
      control of vascular tone. Recently, CNP immunoreactivity and B-type natriuretic
      peptide receptors (NPR-B), for which CNP is a specific ligand, have been
      identified in the kidney. The present study was designed to determine whether
      renal epithelial cells produce and secrete CNP and whether CNP immunoreactivity
      is present in canine kidney. Opossum kidney (OK) cells that express proximal
      tubular cell characteristics were incubated for 6 h in fetal calf serum-free
      Dulbecco's modified Eagle's medium (DMEM). CNP immunoreactivity was measured in
      the preincubation and 6-h conditioned media by radioimmunoassay (RIA) using a
      specific antibody to CNP-22. Furthermore the molecular form of this CNP-like
      protein was determined by reverse-phase high-performance liquid chromatography
      (HPLC), and intracellular localization of the CNP immunoreactivity was determined
      by immunohistochemical staining. CNP immunoreactivity was also determined in
      renal tissue from dogs subjected to saline or endothelin infusion. Six-hour
      incubation in DMEM resulted in accumulation of CNP immunoreactivity (baseline
      below detection level vs. 6 h = 117.3 +/- 8.3 pg/ml, P < 0.001). Intracellular
      CNP concentration determined after sonication was 1.9 +/- 0.2 micrograms/g
      protein, and immunohistochemical staining for CNP was markedly positive in the
      cytoplasm.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7810779
TI  - An analysis of rotator cuff repair.
AB  - Fifty-four patients who had surgery to repair a chronic rotator cuff tear (54
      shoulders) were followed for an average of 25.9 months (range, 16 to 43). Forty
      nine of 54 patients had at least 20 months of followup. The average age of the
      male patients (N = 37) was 52 (range, 24 to 80) and of the female patients (N =
      17) was 56 (range, 38 to 72). All of these patients received a functional
      evaluation based on the Shoulder and Elbow Surgery Society classification system.
      Forty-eight patients had an individual examination and 33 patients had an
      isokinetic strength evaluation. There were 43 patients (80%) with a satisfactory
      functional result and 11 (20%) with an unsatisfactory result. Unsatisfactory
      results were associated with large and massive tears and decreased postoperative
      range of motion. Good functional results were obtained by open repair and
      subacromial decompression for rotator cuff tear. Arthroscopic evaluation and
      treatment did not affect the functional outcome, but it did increase costs by
      about $2000 per patient. Arthroscopy is useful to define tear size, which may
      affect the surgical approach, but the arthroscopic treatment of glenohumeral
      problems did not alter the functional result. The routine use of arthroscopy
      before rotator cuff repair is costly, not effective, and therefore not
      recommended.

PMID- 7810778
TI  - Inferior capsular shift procedure for anterior-inferior shoulder instability in
      athletes.
AB  - Sixty-eight shoulders in 63 athletic patients with anterior-inferior glenohumeral
      instability underwent an anterior-inferior capsular shift procedure. Shoulders
      with glenoid fractures, predominantly posterior instability, or routine,
      unidirectional anterior instability were not included in this study. There were
      42 men and 21 women, with an average age of 23 years. Forty-two repairs were
      performed on the dominant arm. All 31 overhead throwing athletes had their
      dominant arms repaired. Forty-six shoulders had histories of recurrent anterior
      dislocations, while 22 shoulders had recurrent subluxation. All 68 shoulders had
      an anterior-inferior capsular shift, tailored to the degree of laxity found; in
      addition, 21 had repair of a Bankart lesion. Forty-two patients were rated
      excellent (67%), 17 good (27%), 2 fair (3%), and 1 poor (3%). Fifty-eight of 63
      (92%) patients returned to their major sports, 47 (75%) at the same competitive
      levels. Only 5 of 10 elite throwing athletes returned to their prior competitive
      levels. Loss of external rotation averaged 7 degrees. Two patients (2.9%) re
      dislocated postoperatively, after violent falls.

PMID- 7810780
TI  - Arthroscopic Bankart repair versus nonoperative treatment for acute, initial
      anterior shoulder dislocations.
AB  - A prospective study evaluating nonoperative treatment versus arthroscopic Bankart
      suture repair for acute, initial dislocation of the shoulder was undertaken in
      young athletes. All patients met the following criteria: 1) sustained an acute
      first-time traumatic anterior dislocation, 2) no history of impingement or occult
      subluxation, 3) the dislocation required a manual reduction, and 4) no
      concomitant neurologic injury. Thirty-six athletes (average age, 20 years) met
      the criteria for inclusion. Group I patients were immobilized for 1 month
      followed by rehabilitation; they were allowed full activity at 4 months. Group II
      patients underwent arthroscopic Bankart repair followed by the same protocol as
      Group I. Group I consisted of 15 athletes. Twelve patients (80%) developed
      recurrent instability; 7 of the 12 have required open Bankart repair for
      recurrent instability. Group II consisted of 21 patients; 18 patients (86%) had
      no recurrent instability at last followup (average, 32 months; range, 15 to 45)
      (P = 0.001). One patient in Group II has required a subsequent open Bankart
      repair to treat symptomatic recurrence (P = 0.005). In this study, arthroscopic
      Bankart repair significantly reduced the recurrence rate in young athletes who
      sustained an acute, initial anterior dislocation of the shoulder.

PMID- 7810781
TI  - Incidence and mechanisms of acute ankle inversion injuries in volleyball. A
      retrospective cohort study.
AB  - In a retrospective cohort study of ankle inversion injuries performed after the
      1991-1992 season in the top two divisions of the Norwegian Volleyball Federation,
      63 injuries were found among 318 players during 60,612 hours of training and 928
      matches. The study was limited to acute ankle inversion injuries that caused an
      absence of 1 or more days from training or match play. The total injury rate was
      0.9 +/- 0.12 per 1000 player hours: 0.7 +/- 0.11 during training and 2.6 +/- 0.56
      during match play. The relative risk of injury during match play versus training
      was 3.9 (P < 0.001). Women had an injury rate of 1.1 +/- 0.18, whereas that of
      men was 0.7 +/- 0.15 (relative risk = 1.47; not significant). Most of the players
      (78%) had suffered at least one previous injury of the affected ankle. Most
      injuries were mild to moderate. The majority of the injuries (86%) occurred at
      the net, mainly when landing after blocking (63%) or attacking (29%). We suggest
      that simple measures such as rule changes, technical training, and prophylactic
      taping or bracing may lead to a significant reduction in the incidence and
      severity of such injuries.

PMID- 7810782
TI  - A fivefold reduction in the incidence of recurrent ankle sprains in soccer
      players using the Sport-Stirrup orthosis.
AB  - A study was undertaken to evaluate the effect of a semi-rigid ankle orthosis
      (Sport-Stirrup) on the incidence of ankle sprains in soccer players during 1
      playing season. Senior soccer players were divided into 2 groups: players with
      previous ankle sprains (N = 258) and players without such history (N = 246). The
      players in these groups were each randomly allocated to either a semi-rigid
      orthosis or a control group at the start of the playing season. All subsequent
      injuries during the season and the total number of playing hours were documented.
      There was a significant reduction in the incidence of ankle sprains
      (injuries/1000 playing hours) by ankles in the orthosis group with previous
      sprains (0.14) compared with the nonbraced group with previous sprains (0.86).
      The incidence of ankle sprains was significantly higher in the nonbraced group
      with previous sprains (0.86) compared with the nonbraced group without previous
      sprains (0.46). Thus, in this study, a semirigid orthosis significantly reduced
      the incidence of recurrent ankle sprains in soccer players with previous history
      of ankle sprains.

PMID- 7810783
TI  - Immediate free ankle motion after surgical repair of acute Achilles tendon
      ruptures.
AB  - We prospectively studied 17 consecutively treated patients (15 men and 2 women)
      who had surgically treated subcutaneous, complete and acute Achilles tendon
      ruptures. The patients underwent a new postoperative regimen that allowed free
      ankle motion in a patellar tendon bearing plaster cast with a protecting frame
      under the foot making weightbearing possible immediately after surgery.
      Evaluation was done using a patient questionnaire and a clinical examination
      recorded at 6 weeks (when the mobile ankle cast was removed), 3 months, and 1
      year. Measurements of isokinetic and functional strength compared with the
      uninjured leg were performed at the final followup. No rerupture or other
      complications occurred. At 1 year, our patients were graded according to the
      Arner-Lindholm rating scale and there were 15 (88%) excellent, 2 good, and no
      poor results. Six patients had an excellent result already at 3 months, and there
      were no poor results at any evaluation. The patient evaluations showed range of
      motion, strength, and recovery time comparable with or better than results of
      previous studies. Early free ankle motion after repair of Achilles tendon
      ruptures proved safe with very satisfactory clinical results, which justified a
      randomized, prospective study (now in progress) comparing it with traditional
      ankle immobilization.

PMID- 7810784
TI  - Surgical management of Achilles tendon overuse injuries. A long-term follow-up
      study.
AB  - We studied 79 cases of surgically treated Achilles tendon overuse injuries in 66
      patients. Fifty-three (80%) of these patients were competitive or serious
      recreational runners operated on between 1978 and 1991. There were 49 men and 17
      women with a mean age of 33 years (range, 17 to 59). The cases were divided into
      surgical subgroups based on their site of primary symptoms and abnormalities:
      paratenonitis (23), tendinosis (partial rupture or degeneration) (15),
      retrocalcaneal bursitis (24), insertional tendinitis (7), and combined
      abnormalities (10). Followup included a comprehensive patient questionnaire and
      office examination. There were 79% satisfactory (51% excellent, 28% good) and 21%
      unsatisfactory (17% fair, 4% poor) results. The percentages of satisfactory
      results in the paratenonitis group (87%) were best and those in the tendinosis
      group were the worst (67%). Satisfactory results were obtained in 75% of the
      patients with retrocalcaneal bursitis and 86% with insertional tendinitis. Seven
      of the 45 cases with longer than 5-year followup with initially satisfactory
      results deteriorated with time and required reoperation (16%). Of these, 4 were
      in the tendinosis group, 2 had retrocalcaneal bursitis, and 1 had paratenonitis.
      One of the 34 patients followed less than 5 years required reoperation.

PMID- 7810785
TI  - Anterior cruciate ligament reconstruction using the semitendinosus and gracilis
      tendons augmented by the losee iliotibial band tenodesis. A long-term study.
AB  - Seventy patients were evaluated after combined intra- and extraarticular
      reconstruction of the anterior cruciate ligament. Semitendinosus and gracilis
      tendons were used for the intraarticular reconstruction and Losee iliotibial band
      tenodesis for the extraarticular procedure. Minimum followup was 5 years
      (average, 7). Clinical examination and instrumented ligament examination with the
      KT-1000 arthrometer and the Cybex II dynamometer were used to evaluate results.
      Subjectively, patients had no complaints of instability with daily activities;
      93% had no complaints of instability with athletic participation. Clinical
      examination demonstrated that 81% had less than a 1 + Lachman test; 98% had a
      negative pivot shift. Instrumented examination of the anteroposterior limits of
      motion revealed that only 57% had less than 3-mm side-to-side difference; 30% had
      3- to 5-mm; and 13% had 6- to 9-mm. Mean hamstring muscle strength measured with
      the Cybex II dynamometer was 94% at 60 and 96% at 100 deg/sec. When evaluated
      with the Zarins scale, 90% were rated good or excellent, 6% fair, and 4% poor.
      This reconstructive procedure restores functional, but not necessarily normal,
      stability in most anterior cruciate ligament-deficient knees. It allows patients
      to increase activity levels without significant risk of additional injuries.

PMID- 7810786
TI  - The effect of thigh and goniometer restraints on the reproducibility of the
      genucom knee analysis system.
AB  - We compared the reproducibility of measurements made with the Genucom knee
      analysis system using two methods of restraint. The first method was that
      suggested by the manufacturer and consisted of clamping the thigh to the
      examination chair with 70 N of vertical force and 110 N of mediolateral force and
      used a single elastic strap to secure the electrogoniometer cuff to the leg. In
      the second, or enhanced, method, the vertical and mediolateral clamping forces
      were each increased to 156 N, and an additional strap was used to secure the cuff
      to the leg. Tests performed were the anteroposterior stress tests at 20 degrees
      and 90 degrees of knee flexion, and the varus-valgus stress test, the internal
      external rotation stress test, and the medial and lateral pivot shift tests at 20
      degrees. Five normal subjects were installed and tested on 6 different days with
      the manufacturer's suggested securing method and on 12 different days with the
      enhanced securing method. The enhanced method of restraint resulted in
      significantly reduced day-to-day variance for all tests performed except the
      varus-valgus stress test.

PMID- 7810787
TI  - Fate of the ACL-injured patient. A prospective outcome study.
AB  - We followed 292 patients who had sustained an acute traumatic hemarthrosis for a
      mean of 64 months. The KT-1000 arthrometer measurements within 90 days of injury
      revealed the injured knee was stable in 56 patients and unstable in 236. Forty
      five unstable patients had an ACL reconstruction within 90 days of injury.
      Surgical procedures performed > 90 days after injury included ligament
      reconstruction in 46 patients. Factors that correlated with patients who had late
      surgery for a meniscal tear or an ACL reconstruction (P < 0.05) were preinjury
      hours of sports participation, arthrometer measurements, and patient age. Follow
      up data are presented for the patients divided into four groups: I, early stable,
      no reconstruction; II, early unstable, no reconstruction; III, early
      reconstruction; and IV, late reconstruction. No patient changed occupation
      because of the knee injury. Hours per year of sports participation and levels of
      sports participation decreased in all groups. Joint arthrosis was documented by
      radiograph and bone scan. Joint surface injury abnormalities observed at surgery
      and meniscal surgery showed greater abnormalities by radiograph and bone scan
      scores (P < 0.05). Reconstructed patients had a higher level of arthrosis by
      radiograph and bone scan.

PMID- 7810788
TI  - An electromyographic analysis of the knee during functional activities. I. The
      normal profile.
AB  - This study describes the fine-wire electromyographic profile of the normal knee.
      Twenty-two subjects with no prior history of knee injury volunteered for the
      study. Each subject had fine-wire electromyographic evaluation of 8 muscles
      (vastus medialis oblique, vastus lateralis, rectus femoris, semimembranosus,
      biceps femoris, tibialis anterior, gastrocnemius, and soleus muscles) while
      performing 7 functional activities. The percentage of maximum manual test for
      each muscle during each phase of the activities was used to determine means and
      standard deviations for the group. Walking and ramp and stair ascending and
      descending produced similar electromyographic profiles. Running and cross-cutting
      demonstrated unique electromyographic profiles with an overall higher muscle
      activity than the previous 5 activities. A quadriceps-hamstrings muscles'
      coordinated response was identified consistently in each activity. These findings
      illustrate the integral nature of each of the 8 examined muscles in knee motion.
      Furthermore, this study demonstrates a coordinated response of quadriceps
      hamstrings muscles in the normal knee and may more thoroughly define the
      coordinated activity of these 2 antagonist muscle groups. Finally, this study
      provides a framework within which various knee conditions can be compared and
      from which specific rehabilitation recommendations can be generated.

PMID- 7810789
TI  - An electromyographic analysis of the knee during functional activities. II. The
      anterior cruciate ligament-deficient and -reconstructed profiles.
AB  - This study compared the electromyographic activity of normal (N = 22),
      rehabilitated anterior cruciate ligament-deficient (N = 8), and -reconstructed
      knees (N = 10) while subjects performed activities. Each subject had evaluation
      of 8 muscles during 7 functional activities. Sixty-seven percent of the
      differences in the quadriceps muscle reflected increased activity in the vastus
      lateralis muscle of the rehabilitated group; 75% of the differences in the
      hamstrings muscles noted increased biceps femoris muscle activity in the
      rehabilitated group; 56% of the differences in the lower leg musculature showed
      increased tibialis anterior muscle activity in the rehabilitated group. Eighty
      six percent of the statistically different intervals involved rehabilitated
      subjects demonstrating increased activity over reconstructed or normal subjects
      or both. The presence of a quadriceps-hamstrings muscles coordinated response was
      identified consistently in all 3 groups in each activity. This study supports
      surgical reconstruction for the anterior cruciate ligament-deficient knee. It
      also demonstrates the importance of the vastus lateralis, biceps femoris, and
      tibialis anterior musculature in the rehabilitation of the anterior cruciate
      ligament-deficient patient. The presence of a quadriceps-hamstrings muscles
      coordinated response indicates that mechanoreceptors mediating this reflex arc
      exist in structures other than the cruciate ligament.

PMID- 7810790
TI  - Anterior cruciate ligament reconstruction using gracilis and semitendinosus
      tendons. Comparison of through-the-condyle and over-the-top graft placements.
AB  - Eighty-seven patients had anterior cruciate ligament reconstruction using one
      limbed gracilis and semitendinosus tendon graft. No extraarticular or associated
      ligamentous procedures were performed. A 44-patient subgroup was alternated on an
      every-other-case basis between 2 graft placements, either over the top or through
      the femoral condyle; 64 patients (32 of each type) returned for complete
      evaluations. Average followup was 2.9 years. Groups were similar in age, gender,
      injury chronicity, number of meniscectomies, and preoperative activity levels. No
      statistical differences between groups were seen in overall knee rating, range of
      motion, KT-1000 arthrometer measurements, isokinetic muscle testing, or one
      legged hop test. Injured minus normal anterior laxity at 89 N was 2.1 +/- 2.0 mm.
      Isokinetic testing demonstrated an average 95% normal knee extension strength and
      106% normal flexion strength, measured at 60 deg/sec. Average hop index was 95%.
      Eight of 64 patients evaluated demonstrated injured minus normal differences of
      4.5 mm or greater. Three of 8 had frankly positive 2+ and 5 had 1+ pivot shifts;
      however, 4 of these returned fully to sports, and 4 returned with modifications.
      Overall, 55 of 64 patients returned to preinjury sports.

PMID- 7810791
TI  - Histology and arthroscopic anatomy of the ulnar collateral ligament of the elbow.
AB  - The histology and arthroscopic anatomy of the ulnar collateral ligament of the
      elbow were studied in cadaveric specimens. The capsule consists of two layers of
      collagen fibers, with two distinct ligamentous bundles corresponding to anterior
      and posterior portions of the ulnar collateral ligament. The posterior bundle
      consists of distinct collagen bundles within the layers of the capsule; the
      anterior bundle consists of a similar thickening within the capsular layers, with
      an additional ligament complex superficial to the capsular layers. With
      arthroscopy only the anterior 20% to 30% of the anterior bundle of the ulnar
      collateral ligament could be visualized via the anterior portal. Only the
      posterior 30% to 50% of the posterior bundle could be seen via the posterior
      portals. After sectioning of the anterior bundle, joint instability was noted
      arthroscopically by an increased opening in the ulnohumeral joint with
      application of valgus stress. At arthroscopy ulnar collateral ligament tears may
      be visualized in part or not at all. To diagnose a tear or laxity in the ulnar
      collateral ligament, a demonstration of an increase in the opening of the
      ulnohumeral joint in response to valgus stress is useful.

PMID- 7810792
TI  - Medial epicondylitis. An electromyographic analysis and an investigation of
      intervention strategies.
AB  - Flexor and extensor muscle-tendon unit activity at the elbow during the golf
      swing was recorded from subjects with and without medial epicondylitis. There was
      no significant difference in total swing time between symptomatic (1.23 +/- 0.15
      sec) and asymptomatic (1.15 +/- 0.13 sec) subjects nor between golfers with low
      (1 to 6 handicap, N = 8) and high (11 to 19 handicap, N = 8) scoring abilities.
      Symptomatic and asymptomatic subjects displayed similar electromyographic
      profiles for flexor and extensor muscles of the forearm. Electromyographic
      activity of the common extensor muscles was persistent throughout the four swing
      phases, ranging from 33.59% of maximum voluntary contraction at address to 58.77%
      at contact. Common flexor muscles produced a consistent burst of
      electromyographic activity during contact phase (flexor burst, 90.77% of maximum
      voluntary contraction). Symptomatic subjects' mean flexor muscle
      electromyographic activity was significantly greater than that of asymptomatic
      subjects in both address and swing phases. When forearm brace and oversized grips
      were imposed on symptomatic subjects, there was no significant difference in mean
      electromyographic magnitude or muscle activation pattern during the golf swing.
      Thus, the method of symptomatic relief of the intervention strategies tested is
      still in question.

PMID- 7810793
TI  - The diagnosis and treatment of medial subluxation of the patella after lateral
      retinacular release.
AB  - Five patients with medial subluxation of the patella occurring after isolated
      lateral retinacular release were treated between July 1985 and July 1989. The
      diagnosis was made by clinical examination. The patients complained of pain,
      swelling, and giving way after the lateral release. All five patients had
      increased medial passive patellar mobility, a positive gravity subluxation test,
      and a positive medial apprehension test. All patients failed conservative
      treatment. The patients were treated by reconstruction of the lateral retinaculum
      using sensory epidural anesthesia. At an average followup of 3.3 years, four of
      the five patients had no symptoms of instability and the medial patellar mobility
      and gravity subluxation tests were negative. There were three excellent and two
      good results using the grading system of Merchant and Mercer.

PMID- 7810794
TI  - Rupture of Lisfranc's ligament in athletes.
AB  - Ligamentous injuries to the tarsometatarsal joints are uncommon and usually
      result from violent trauma to the forefoot. A more subtle tarsometatarsal injury
      consisting of an isolated diastasis of the first and second tarsometatarsal rays
      has recently been described. This injury is thought to be caused by a rupture of
      Lisfranc's ligament. Nine injuries that occurred during athletics are described.
      History and physical findings are crucial for arousing the clinician's suspicion
      for this injury, but confirmation can best be obtained by comparison weight
      bearing radiographs; the space between the first and second metatarsal bases may
      be widened 2 to 5 mm. Nonoperative treatment consisting of casting and the use of
      crutches for 4 to 6 weeks was successful in returning patients back to athletics;
      however, the time to return to competition averaged 4 months.

PMID- 7810795
TI  - Isolated rupture of the patellar tendon in athletes.
AB  - The purpose of this study was to review patellar tendon ruptures in athletes
      treated with surgical repair. Six patellar tendon ruptures in five athletic
      patients were identified at our institution between 1980 and 1990. All patients
      had operative debridement and primary repair of the ruptured patellar tendon
      using nonabsorbable sutures passed through patellar drill holes at an average of
      2.5 days after injury. Personal interview, physical examination, roentgenographic
      evaluation, and isokinetic strength testing were performed at an average of 6
      years after surgery. At final followup, no patient had complaints referable to
      the patellar tendon repair; all were able to achieve their premorbid levels of
      sports at an average of 18 months after injury. No patient thought that the
      surgically repaired knee was unstable or activity-limiting. All patients
      demonstrated full range of motion and strength equal to or greater than that of
      the noninjured side. One patient required an arthroscopic lateral release for
      lateral patellar facet pressure syndrome with an excellent result. No
      complications occurred; no other reoperations were required. Complete disruption
      of the patellar tendon is an uncommon injury in athletic individuals without
      predisposing medical conditions. After acute operative repair and aggressive
      rehabilitation, an excellent and enduring functional outcome can be expected.

PMID- 7810796
TI  - Effect of bone block removal and patellar prosthesis on stresses in the human
      patella.
AB  - Thermoelastic stress analysis was used to examine stresses on the anterior
      surface of patellae after patellar bone block excision for autogenous graft
      anterior cruciate ligament reconstruction. Complications of anterior cruciate
      ligament injury often lead to degenerative changes in the knee that can require
      total knee joint replacement. It was hypothesized that stresses in a bone block
      compromised patella may be increased even further by insertion of a patellar
      prosthesis. All patellae were first tested intact and then were retested after a
      sequence of surgical modifications including patellar prosthesis implantation,
      tapered bone block excision, square bone block excision, and both shapes of
      excised bone blocks with a patellar prosthesis in place. Stresses in patellae
      with bone blocks excised were significantly greater than stresses in intact
      patellae. The anterior surface stress pattern in the loaded patella was
      significantly altered by excision of a bone block. There were no significant
      differences between maximum stress in patellae with tapered and square bone
      blocks excised. A finite element analysis showed that excision of a larger
      trapezoid-shaped bone block greatly increased maximum stress levels. Insertion of
      a patellar prosthesis did not significantly alter stress patterns or maximum
      stress levels in the patella.

PMID- 7810797
TI  - A muscle contusion injury model. Biomechanics, physiology, and histology.
AB  - We developed a reproducible muscle contusion injury and studied its effect on
      contractile function, histology, and passive failure. An instrumented drop-mass
      technique (mass, 171 g; height, 102 cm; spherical radius, 6.4 mm) delivered a
      single impact to the posterior surface of the gastrocnemius muscle in one limb of
      40 male Wistar rats. On Day 0, the impact significantly (N = 12, P < 0.01)
      decreased maximum tetanic tension to 63% of the contralateral control value.
      Histologic examination demonstrated extravasation of erythrocytes, edema,
      myofiber disruption, and vacuolation of myofibers. Passive failure initiated at
      the site of injury. At 2 days, tetanic tension was 75% of controls (N = 11, P <
      0.01). Histologically, acute inflammation and phagocytosis were noted. Tetanic
      tension at 7 days was 81% of controls (N = 8, P < 0.01). Vimentin staining
      indicated a dramatic increase in myoblast activity. Contractile strength was near
      normal at 24 days. Histologic examination showed complete regeneration of normal
      striated muscle fibers. No vimentin activity was found. No passive failures
      initiated at the injury site. Contusion injury produced a significant deficit in
      contractile function that continually diminished with gross histologic evidence
      of degeneration, regeneration, and normalization at the injured muscle fibers.

PMID- 7810798
TI  - Alternative management of midthird scaphoid fractures in the athlete.
AB  - The purpose of this retrospective study was to evaluate the effectiveness of two
      scaphoid fracture treatments in an athletic population. All patients were in
      season athletes with a stable, midthird scaphoid fracture incurred in preseason
      training or early in the season, or athletes who had a consecutive season sport.
      Group I athletes (N = 18) were treated with immediate open reduction and internal
      fixation with the Herbert screw. Group II athletes (N = 12) were treated
      nonoperatively with a playing cast. Return to sports averaged 8.0 weeks for Group
      I and 4.3 weeks for Group II athletes. Six athletes in Group II were able to
      return to play immediately with the playing cast. Clinical and radiographic
      healing averaged 10.8 and 11.2 weeks for Group I and 13.7 and 14.2 weeks for
      Group II athletes, respectively. In-season athletes with stable midthird scaphoid
      fractures can safely achieve early return to sport with a playing cast or rigid
      internal fixation with a Herbert screw. These methods of treatment yield
      comparable union rates with other series and it appears the athletes are not at
      increased risk for union failure or nonunion secondary to participation in
      sports.

PMID- 7810799
TI  - Soft tissue reconstruction in the shoulder. Comparison of suture anchors,
      absorbable staples, and absorbable tacks.
AB  - We evaluated three mechanical soft tissue fixation devices (SuperAnchor, Suretac,
      and the Instrument Makar [IM] Bioabsorbable Staple) in a cadaveric model by
      examining ultimate tensile failure and modes of failure in simulated Bankart
      repairs. We attempted to realistically evaluate the strengths of soft tissue
      reattachment procedures at the anterior glenoid under worst-case conditions--load
      to failure. Twenty fresh-frozen cadaveric shoulders were used in this
      investigation. Each of the three techniques was performed in each anterior
      glenoid rim at one of three locations: superior, middle, or inferior. The
      subscapularis muscle-tendon was harvested, used in the repair, and loaded to
      failure. The mean load at failure for the SuperAnchor was 217.32 N; for the IM
      Staple, 132.32 N; and for the Suretac, 122.37 N. A two-sample t-test demonstrated
      that the load at failure for the SuperAnchor was statistically greater (P <
      0.001) when compared with the IM Staple and Suretac. There was no statistical
      difference between load at failure for the Suretac and the IM Staple. The most
      common failure mode for the Mitek was suture breakage (71%). Anchor pullout from
      bone was the most common failure mode for the IM Staple (75%) and Suretac (94%).

PMID- 7810800
TI  - Survey of health care coverage of high school football in southern California.
AB  - We surveyed 240 high schools about various aspects of the health care coverage of
      their football athletes. Approximately 70% of these schools had team physicians,
      and more than one third of these had more than 1 team physician. Seventy-two
      percent of high schools had physician coverage for scheduled games. Practices and
      scrimmages were not covered. Sixty-nine percent of the schools reported having an
      athletic trainer for home games. Basic equipment was often lacking. Recording and
      tracking of athletic injuries were inconsistent. An overall team approach for
      medical coverage was noted. Concern was raised about adequate physician or
      medical coverage with emphasis on greater input from the school administration,
      community hospitals, and physicians.

PMID- 7810801
TI  - Use of the suture anchor in open Bankart reconstruction. A follow-up report.
AB  - We previously reported early results of a new technique using a suture anchor to
      perform a modified Bankart reconstruction. That study included patients from two
      medical centers and had an average followup of only 1 year. This report includes
      patients from a single center with followup extended to a mean of 42 months
      (range, 33 to 61). Between April 1988 and August 1991, 53 patients with recurrent
      anterior glenohumeral instability underwent modified Bankart reconstruction with
      the use of a suture anchor. Thirty-two patients met inclusion criteria
      (identifiable Bankart lesion, open repair with suture anchors, and minimum
      followup of 2 years); 4 patients were lost to followup. There have been no
      complications as a result of this technique. Ninety-three percent of the patients
      in the study had objectively excellent or good results. There were 2 failures
      with recurrent anterior dislocation. The use of a suture anchor can simplify the
      Bankart reconstruction. At average followup of 3 years, 26 patients have returned
      to presurgery activity levels without recurrent dislocation or subluxation.
      However, careful attention to anchor placement at the junction of articular
      cartilage and the glenoid neck is necessary to avoid technical failure.

PMID- 7810802
TI  - Cervical spinal stenosis and stingers in collegiate football players.

PMID- 7810803
TI  - Protective immunity induced in squirrel monkeys with recombinant apical membrane
      antigen-1 of Plasmodium fragile.
AB  - Saimiri sciureus boliviensis monkeys were immunized with the Plasmodium fragile
      form of the merozoite apical membrane antigen-1 produced using the baculovirus
      expression system and combined with Montanide ISA 720 adjuvant. Following three
      immunizations, monkeys were challenged with 10,000 P. fragile trophozoite
      parasites. Antibody titers determined by fluorescence microscopy indicated an
      enhanced response following the second immunization. Four of five control animals
      had parasite counts > 5% 18-26 days following challenge. Four of five immunized
      monkeys had reduced levels of maximum parasitemia or delays in accumulated
      parasite counts, suggestive of protection. Rechallenge of the animals with P.
      falciparum resulted in three of four adjuvant control animals developing patent
      parasitemia whereas none of five immunized animals were infected, suggesting some
      level of heterologous protection.

PMID- 7810804
TI  - Immunologic responses to soluble exoantigens of Plasmodium falciparum in Gabonese
      children exposed to continuous intense infection.
AB  - The development of antidisease immunity in children infected with Plasmodium
      falciparum is thought to be related to their immunologic responses to certain
      soluble parasite-derived exoantigens. We have assessed both cellular and humoral
      responses to these antigens in a cross-sectional study of a cohort of Gabonese
      schoolchildren who live in an area where malaria is holoendemic and perenially
      transmitted, in an attempt to identify immunologic markers of this early
      developing protective immunity. Concurrent parasitemia was found to have a
      significant influence on lymphoproliferative and antibody responses to the
      exoantigens. Individuals with higher levels of parasitemia had significantly
      lower proliferative and IgG isotype responses. Higher concentrations of specific
      IgG1 and IgG3, in particular, were associated with lower or no parasitemia,
      suggesting a possible protective role for these isotypes, whereas the level of
      IgM antibodies showed a trend towards higher concentrations in those with
      parasitemia, perhaps indicative of an exoantigen-induced T cell-independent
      response. Cytokine responses were unaffected by either the presence or the
      intensity of parasitemia and were dissociated from both proliferative and
      antibody response to the exoantigens. However, the mitogen-stimulated production
      of tumor-necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL)-6 was
      positively correlated with the corresponding lymphoproliferative responses. At
      the individual level, mitogen-stimulated TNF-alpha, interferon-gamma, IL-2, and
      IL-6 responses were positively correlated, as were mitogen- and exoantigen
      induced TNF-alpha. The results are discussed in the light of current knowledge of
      immune responses to the exoantigens and the development of protective immunity to
      P. falciparum.

PMID- 7810805
TI  - High prevalence of natural antibodies against Plasmodium falciparum 83-kilodalton
      apical membrane antigen (PF83/AMA-1) as detected by capture-enzyme-linked
      immunosorbent assay using full-length baculovirus recombinant PF83/AMA-1.
AB  - The 83-kilodalton (kD) apical membrane antigen of Plasmodium falciparum (PF83/AMA
      1) is a potential asexual blood stage vaccine component. This antigen has been
      expressed as a full-length, nonfusion, recombinant baculovirus protein (PF83-7G8
      1) using the authentic predicted signal peptide for appropriate postsynthetic
      routing. When purified by a novel high-performance, ion exchange chromatography
      (HPIEC) method, PF83-7G8-1 induced polyclonal antibodies in rats that
      immunoprecipitated both 83- and 66-kD forms of PF83/AMA-1 from 35S-methionine
      metabolically labeled parasite extracts. Using HPIEC-purified PF83-7G8-1 in
      combination with a rat monoclonal antibody against the highly conserved carboxy
      terminal (CT) region of PF83/AMA-1, we developed a CT-capture-enzyme-linked
      immunosorbent assay to measure naturally acquired responses against the entire
      PF83/AMA-1 molecule. Analysis of populations from villages in Guinea-Bissau and
      in an area of high malarial transmission in Senegal demonstrated a very high
      prevalence (94-100%) of naturally acquired serum IgG responses to PF83/AMA-1.
      Analysis of these natural responses showed that PF83/AMA-1 may be a well
      recognized asexual parasite antigen. A statistically significant age-related
      change in antibody levels to PF83/AMA-1 was observed in Guinea-Bissau. No such
      correlation was observed in the Senegalese population, although an age-related
      antibody response was seen for total parasite antigen. No significant correlation
      was observed between PF83/AMA-1 responses and the parameters of parasite load and
      malaria-related fever.

PMID- 7810806
TI  - Immunoglobulin G subclass responses in human cystic and alveolar echinococcosis.
AB  - Immunoglobulin G (IgG) subclass-specific antibody responses were investigated in
      both human cystic echinococcosis (CE) and alveolar echinococcosis (AE) by enzyme
      linked immunosorbent assay (ELISA) and Western blotting. Sera were tested from 81
      CE and 50 AE surgically confirmed cases using partially purified hydatid cyst
      fluid antigen B (EgB), and crude hydatid cyst fluid (EgCF) from Echinococcus
      granulosus and a protoscolex extract (EmP) prepared from E. multilocularis
      metacestodes. Eighty-nine percent of CE patients and 94% of AE patients were
      seropositive for total IgG antibodies. The dominant IgG antibody isotype in both
      CE and AE was IgG4, for which 73% of CE and 84% of AE cases were seropositive in
      the ELISA. Anti-Echinococcus IgG1 antibodies were detected in 58% of CE and 84%
      of AE patients. Sensitivity for IgG2 and IgG3 was significantly lower for both CE
      and AE patients. The IgG4 antibodies in CE patients predominantly recognized the
      E. granulosus antigen B subunits, i.e., at 20, 16 and 12 kD, while IgG1
      antibodies primarily bound to the 38-kD subunit of antigen 5 from E. granulosus
      hydatid fluid. The possible functional significance of an IgG4 response and the
      potential use of combined assessment of total IgG, IgG1, and IgG4 antibodies in
      serologic diagnosis and follow-up for human echinococcosis are discussed.

PMID- 7810807
TI  - Leishmania major-like parasite, a pathogenic agent of cutaneous leishmaniasis in
      Paraguay.
AB  - Leishmania parasites isolated from two patients with cutaneous leishmaniasis from
      geographically different localities in Paraguay have been characterized by enzyme
      electrophoresis (zymodeme) and digestion profiles of kinetoplast DNA with
      restriction enzymes (schizodeme). Both Paraguayan isolates showed identical
      zymodeme profiles to each other using 14 enzymes (glutamic pyruvate transaminase,
      glutamic oxaloacetic transaminase, enolase, fumarate hydratase, glucose phosphate
      isomerase, glucose-6-phosphate dehydrogenase, malate dehydrogenase, malic enzyme,
      mannose phosphate isomerase, nucleoside phosphorylase, peptidase-D, 6
      phosphogluconate dehydrogenase, phosphoglucomutase, and pyruvate kinase).
      Although two Paraguayan isolates showed different zymodeme profiles from those of
      six Leishmania reference strains of Old and New World Leishmania species, they
      showed identical zymodeme profiles to those of an L. major-like parasite from
      Ecuador. These observations were confirmed by schizodeme analysis using three
      restriction endonucleases (Msp I, Hae III, and Taq I). These results indicate
      that Leishmania parasites isolated in Paraguay are identified as an L. major-like
      parasite, and it is necessary to consider the existence of L. major-like
      parasites when classifying Leishmania isolates from the New World.

PMID- 7810808
TI  - Paromomycin resistance in Leishmania tropica: lack of correlation with mutation
      in the small subunit ribosomal RNA gene.
AB  - The aminoglycoside antibiotic paromomycin is a potentially useful anti
      leishmanial chemotherapeutic agent. Resistance to this antibiotic was studied
      using Leishmania tropica. Promastigotes resistant to 210 micrograms/ml of
      paromomycin were selected by exposing them to gradual increments of this drug.
      Previous work in Escherichia coli, Tetrahymena, and yeast mitochondrial mutants
      has demonstrated mutations in the E. coli small subunit ribosomal RNA at the
      1409:1491 basepair position, or equivalent positions in other organisms,
      resulting in basepair disruption. When the nucleotide sequence at both the DNA
      and RNA levels of the resistant L. tropica promastigotes cultured in the presence
      of paromomycin was compared with those of the drug-sensitive parent, there was no
      sequence change at the putative mutation site. Paromomycin resistance in L.
      tropica is apparently due to other mechanisms.

PMID- 7810809
TI  - Reduced longevity and fecundity in Leishmania-infected sand flies.
AB  - Phlebotomus papatasi and P. langeroni were infected with Leishmania major and L.
      infantum by membrane feeding. Each sand fly ingested approximately 200 parasites
      per blood meal. Higher mortality in both sand fly species was seen with mixed
      infections than with a single parasite species. There was no significant
      difference between infections with either L. major or L. infantum in their
      natural vectors or experimental hosts. Infection significantly depressed the mean
      number of eggs laid per female.

PMID- 7810810
TI  - Use of a simplified polymerase chain reaction procedure to detect Trypanosoma
      cruzi in blood samples from chronic chagasic patients in a rural endemic area.
AB  - The feasibility of using DNA amplification by the polymerase chain reaction (PCR)
      for specific detection of Trypanosoma cruzi in human blood specimens was
      investigated. One hundred blood samples were collected in an endemic area of
      Minas Gerais, Brazil. They were submitted to DNA extraction and PCR amplification
      with kinetoplast DNA-specific primers using a simplified boiling procedure that
      linearized most minicircle molecules without the aid of chemical reagents.
      Samples that gave negative results were checked for possible inhibition of
      amplification using primers derived from a human-specific sequence, and those
      showing some level of inhibition were retested after a new DNA extraction. Of 86
      patients previously diagnosed as chagasic by serologic techniques, 83 were
      positive in our PCR test (sensitivity = 96.5%), including all the xenodiagnosis
      positive patients and 21 (87.5%) of 24 xenodiagnosis-negative individuals. In
      addition, four of six patients with doubtful serologic results were confirmed as
      positive by PCR. Our results suggest that the PCR may be a useful complement to
      serology in the diagnosis of Chagas' disease, and that it is the most powerful
      technique available for parasite detection in patients with chronic disease.

PMID- 7810811
TI  - Comparison of capillary whole blood, venous whole blood, and plasma
      concentrations of mefloquine, halofantrine, and desbutyl-halofantrine measured by
      high-performance liquid chromatography.
AB  - Whole blood mefloquine, halofantrine, and desbutyl-halofantrine concentrations
      were measured by high-performance liquid chromatography in capillary blood,
      venous blood, and venous plasma samples from patients along the Thai/Burmese
      border with falciparum malaria who were treated with either mefloquine (25 mg/kg)
      or halofantrine (24 mg/kg or 72 mg/kg). The limits of detection for mefloquine,
      halofantrine, and desbutyl-halofantrine were 50, 15, and 10 ng/ml, respectively,
      with 200 microliters whole blood samples. There was a good linear correlation (r
      > 0.9) between capillary and venous blood and between whole blood and plasma for
      all three compounds. Mefloquine concentrations in venous and capillary blood were
      very similar (mean ratio 1.02, 95% confidence intervals [CI] 0.95-1.09, n = 60),
      but were 1.15 times higher (95% CI 1.03-1.29) in whole blood than in plasma (n =
      22). The halofantrine and desbutyl-halofantrine concentrations were 1.27 (1.12
      1.45, n = 23) and 1.34 (1.16-1.55, n = 24) times higher in venous compared to
      capillary blood, while halofantrine but not desbutyl-halofantrine concentrations
      were lower in whole blood than in plasma (mean ratios: halofantrine: 0.83 [0.72,
      0.94], n = 39 and desbutyl-halofantrine: 1.05 [0.96-1.15], n = 41). Measurement
      of mefloquine, halofantrine, or desbutyl-halofantrine in capillary blood is an
      accurate and practical alternative to venous blood sampling, and is particularly
      useful for sampling with children, and under field conditions when technical
      facilities are limited.

PMID- 7810812
TI  - The pharmacokinetics of a single dose of artemisinin in healthy Vietnamese
      subjects.
AB  - The pharmacokinetics of artemisinin was studied in 12 healthy male Vietnamese
      subjects after a single, 500-mg, oral dose. A total of 14 plasma samples per
      subject was obtained up to 48 hr after drug intake. Measurement of artemisinin
      concentration was performed by high-performance liquid chromatography with
      electrochemical detection. Tolerance was evaluated by recording subjective and
      objective findings including repeated physical examination, routine blood
      investigation, and electrocardiograms. Fitting of the concentration-time curve
      and pharmacokinetic calculations revealed the following results: a mean +/- SD
      volume of distribution/dose ratio of 19.4 +/- 6.9 L/kg, a mean +/- SD absorption
      half-life of 0.58 +/- 0.54 hr with a mean +/- SD calculated maximum concentration
      of 391 +/- 147 micrograms/L occurring at 1.81 +/- 0.73 hr after drug intake.
      Elimination was rapid, with a mean +/- SD elimination half-life of 2.59 +/- 0.55
      hr. Peak concentrations were sufficient with regard to antimalarial activity
      although bioavailability appears to be very low. The relatively small
      interindividual variation in pharmacokinetics does not seem to be of clinical
      significance. Tolerance to the single dose of artemisinin was good: no adverse
      effects were detected. Based on these results, a treatment schedule of 2 x 500 mg
      of artemisinin (oral dose) per day can be advised. This will result in adequate
      antimalarial plasma concentrations, despite poor bioavailability, and rapid
      elimination.

PMID- 7810813
TI  - Filariasis testing in a jird model: new drug leads from some old standbys.
AB  - A total of 65 compounds, most of which were from chemical classes having members
      known to be active against one or more parasitic organisms, were evaluated
      against Brugia pahangi and Acanthocheilonema viteae for macrofilaricidal activity
      in male Mongolian jirds (Meriones unguiculatus). Sixteen of the 65 compounds
      tested suppressed the number of parasites. Of these 16, three were suppressive
      for B. pahangi, 10 for A. viteae, and three for both parasites. The antibiotic
      nigericin and the antihistaminic isothipendyl were found to be most active.

PMID- 7810814
TI  - The effect of antibiotic- and hydrocortisone-containing ointments in preventing
      secondary infections in guinea worm disease.
AB  - A randomized, single-blind, controlled study comparing the efficacy of an
      ointment containing two antibiotics, one containing one antibiotic plus
      hydrocortisone, and no treatment in reducing secondary infections in patients
      with patent Guinea worm was undertaken in the northern region of Ghana. Seventy
      seven patients were included. Time to complete healing was significantly shorter
      in the treatment groups compared with the controls (P = 0.044 and P = 0.003,
      respectively). Secondary infections occurred more often in the controls (P =
      0.00014). Ointments containing antibiotics are recommended for application at the
      early stage of patent Guinea worm infection.

PMID- 7810815
TI  - Evaluation of ultrasonography for the detection of drug-induced changes in
      onchocercal nodules.
AB  - Clinical trials of macrofilaricidal drugs against Onchocerca volvulus are impeded
      due to the lack of means for assessing in vivo drug-induced changes in the
      onchocercomas. The application of ultrasonography in the sequential monitoring of
      morphologic alterations of onchocercal nodules after six weeks of suramin therapy
      was evaluated in 20 male patients from Ghana with a total of 64 nodule sites.
      After each follow-up session, a number of onchocercal nodules were extirpated so
      that by the end of one year, all nodules had been removed for histologic
      examination. The sonomorphologic changes observed and their time of appearance
      correlated well with the histologic findings of the onchocercomas. Eighty-three
      percent of the onchocercal nodules became hyperechogenic and 22% developed echo
      free areas at the end of the follow-up period. Absence of the lateral acoustic
      shadow increased by more than 30% and the lack of differentiation of the worm
      center from the capsule and the nodule from its surrounding tissue increased by
      the end of one-year posttreatment to 100% and 91%, respectively. A mean reduction
      of nodule size of 27% was also documented. The histologic studies revealed that
      the proportion of the dead female worms increased from 17% at the end of the
      suramin therapy to 48% six months later and reached 61% at one year. It is
      concluded that ultrasonographic monitoring of onchocercomas can provide essential
      information on drug effects and facilitate clinical trials of macrofilaricidal
      drugs, limiting histologic evaluation to a few objectively selected
      onchocercomas.

PMID- 7810816
TI  - Clinical and pharmacokinetic study of praziquantel in Egyptian schistosomiasis
      patients with and without liver cell failure.
AB  - The pharmacokinetics and therapeutic efficacy of praziquantel (Distocide; Epico,
      El-Asher-Men-Ramadan City, Egypt) were studied in 40 patients with
      schistosomiasis mansoni and various degrees of hepatic dysfunction. The patients
      were allocated into four groups: the first included 10 patients with simple
      active schistosomiasis while the other three were made up of patients with
      schistosomiasis associated with liver cirrhosis and splenomegaly according to
      Child's classification of hepatocellular function. Every patient was treated with
      40 mg/kg of praziquantel as a single oral dose. The efficacy of the drug was
      evaluated after two months by rectal snip examination. The pharmacokinetic
      parameters did not differ significantly between patients with simple active
      schistosomiasis (group 1) and those with hepatosplenomegaly with liver
      involvement but without ascites and jaundice (group 2). However, as liver cell
      dysfunction became more evident (groups 3 and 4), pharmacokinetic parameters of
      praziquantel such as the half-life of elimination, the half-life of absorption,
      the maximum concentration, the time to maximum concentration, and the area under
      the concentration-time curve increased proportional to the degree of hepatic
      insufficiency. Linear correlations were found between each of the these
      parameters on the one hand and hepatic function test results (total bilirubin,
      direct bilirubin, and serum albumin) on the other. In spite of these
      pharmacokinetic differences, the cure rates were 70%, 80%, 90%, and 90% in the
      four groups, respectively. Although the incidence of side effects was high (53%),
      such effects were transient and mild.

PMID- 7810817
TI  - A case report of serologically diagnosed pulmonary anisakiasis with pleural
      effusion and multiple lesions.
AB  - The second known human case of pulmonary anisakiasis is reported. A 22-years-old
      man living in Hyuga City, Miyazaki Prefecture, Japan, developed high fever,
      respiratory distress, and pleural effusion after consumption of raw fish.
      Although his total white blood cell count increased to approximately 10,000
      20,000/mm3, eosinophilia was not observed. The total IgE level in his serum
      markedly increased up to 3,599 IU/ml. Since the patient was suspected to have a
      parasitic disease, immunoserologic tests were carried out. Screening tests using
      a multiple dot-enzyme-linked immunosorbent assay (ELISA) and an Ouchterlony
      double-diffusion test showed that his serum and pleural effusion had the
      strongest reactivity against crude antigen of Anisakis type I larvae, together
      with weak cross-reactivity against several other nematode antigens. Since
      extragastrointestinal anisakiasis was strongly suspected, this diagnosis was
      confirmed by a microplate-ELISA and Western blot analysis using a monoclonal
      antibody.

PMID- 7810818
TI  - Envenomation by the hump-nosed viper (Hypnale hypnale).
AB  - We carried out a prospective clinical study from June to December 1993 at the
      Base Hospital in Avissawella, Sri Lanka to determine the clinical features of
      envenomation by the hump-nosed viper (Hypnale hypnale). Sixty-two consecutive
      adult patients (63% males and 37% females, with a median age of 30 years [age
      range 13-68 years]) admitted to the medical unit following hump-nosed viper bites
      were surveyed. Most (85.48%) of the patients were bitten on the feet, while
      14.52% of the patients were bitten either on the hands or forearms. Most (61.29%)
      of the patients were bitten during the evening hours (6:00-10:00 PM). The mean
      time for admission to the hospital following the bite was 1.5 hr (range 0.25-13
      hr). All patients had signs of local envenomation manifested by pain, swelling,
      and induration at the site of the bite, which was occasionally associated with
      local hemorrhagic blister formation (11.29%) and regional lymphadenopathy
      (24.19%). None of the patients had signs of systemic envenomation.

PMID- 7810819
TI  - Endemic kala-azar in eastern Sudan: a longitudinal study on the incidence of
      clinical and subclinical infection and post-kala-azar dermal leishmaniasis.
AB  - Between April 1991 and April 1993, a longitudinal study was performed in the
      village of Um-Salala (1,430 inhabitants) in the endemic area of kala-azar
      (visceral leishmaniasis) in eastern Sudan. During the two years, a total of 92
      kala-azar cases were diagnosed (male:female ratio = 1.8:1, mean age 6.6 years).
      The annual incidence rates were 38.4/1,000 and 38.5/1,000 person-years,
      respectively. The ratio of clinical to subclinical cases was 1.6:1 in the first
      year and 2.4:1 in the second year. Post-kala-azar dermal leishmaniasis occurred
      in 48 (56%) of 85 kala-azar cases that were followed-up for at least six months.
      Kala-azar occurred only in previously leishmanin-negative individuals. The
      majority of the population had a positive leishmanin skin test result, probably
      due to previous exposure to Leishmania major causing cutaneous leishmaniasis in
      their homeland in western Sudan from which they had migrated in the 1980s. It was
      thus postulated that previous cutaneous leishmaniasis might protect against kala
      azar but this could not be proved.

PMID- 7810820
TI  - Seroepidemiologic screening of Echinococcus multilocularis infection in a
      European area endemic for alveolar echinococcosis.
AB  - In a serologic survey for Echinococcus multilocularis infection, we screened sera
      from 7,884 subjects from the Doubs Departement in France, an area endemic for
      alveolar echinococcosis (AE) of the liver. An enzyme-linked immunosorbent assay
      (ELISA) with a highly species-specific antigen (Em2) and an E. multilocularis
      crude antigen (Emc) was used for screening. An evaluation of the cost/benefit
      relationship of this screening, followed by therapeutic management of patients,
      was made and compared with the actual cost of the follow-up and treatment of the
      disease in symptomatic cases in this endemic area. Antibody reactions to Em2
      and/or Emc made possible the detection of eight asymptomatic clinical cases
      (seroprevalence averaging 1/1,000), with typical lesions of active AE revealed by
      abdominal ultrasonography and computed tomography. All were seropositive using
      the Emc ELISA but two were seronegative using the Em2 ELISA. In five additional
      seropositive cases, the radiologic investigations revealed small calcified
      lesions similar to the lesions of abortive AE previously found in Alaska. The
      cost of this serologic screening program per screened subject and per diagnosed
      case averaged 50.00 French Francs (FF) (U.S. $8.60) and 60,000.00 FF (U.S.
      $10,909.00), respectively. The cost of diagnosis, follow-up and treatment of the
      patients was 5,086.00 FF (U.S. $929.00) per patient per month in the case of
      diseases diagnosed by the screening program and 7,086.00 FF (U.S. $1,288.00) per
      patient per month for patients with symptomatic AE. This survey indicates a high
      prevalence of AE in the target area; it confirms the long latency period of the
      larval growth in human AE and shows that abortive AE is present in Europe. The
      use of both the Emc and Em2 ELISAs seems to be better than using the Em2 ELISA
      alone. The cost of the hospitalization and treatment of the eight screened
      patients would appear to be relatively high. Even though two of them were
      asymptomatic, they had very severe forms of the disease. In fact, the total cost
      was much lower than the actual cost of the disease when diagnosed from clinical
      symptoms.

PMID- 7810821
TI  - Use of sentinel pigs to monitor environmental Taenia solium contamination. The
      Cysticercosis Working Group in Peru (CWG).
AB  - We tested a novel approach to assay Taenia solium prevalence using the enzyme
      linked immunoelectrotransfer blot assay in sentinel piglets to determine
      environmental contamination with T. solium eggs in a disease-endemic zone in
      Peru. Twelve sentinel piglets from an area where the disease is not present were
      tested at two months of age, moved to an area where the disease is endemic, and
      retested at the of age nine months. Sentinel piglets native from this T. solium
      endemic area were also tested concurrently at two and nine months of age. Of the
      non-native pigs, 33% (4 of 12) acquired new infection. Of the 28 native pigs
      tested, 64% (18 of 28) acquired the infection. In a subset of the native piglets
      from seronegative sows, 44% (4 of 9) were infected at five months of age.
      Serodiagnosis of sentinel piglets is a practical method to detect T. solium eggs
      in the environment. Furthermore, it permits indirect assessment of human risk,
      which may be useful for monitoring the efficacy of intervention programs.

PMID- 7810823
TI  - Plasmodium falciparum circumsporozoite antibody prevalence in Madagascar: a
      longitudinal study in three different epidemiologic areas.
AB  - A longitudinal study on the prevalence of Plasmodium falciparum circumsporozoite
      antibodies (Ab-CS) was carried out in 15 villages of three epidemiologic areas of
      Madagascar: the highlands, east coast, and the southwest region. A total of 3,967
      blood samples were collected from November 1989 to April 1991 from cohorts of
      resident schoolchildren. The prevalence of Ab-CS in the examined population
      varied greatly according to the different ecoepidemiologic areas of the country.
      A correlation analysis was made between Ab-CS and P. falciparum parasite
      prevalence in the same population. High Ab-CS prevalence rates (25-75%) and
      levels (optical density = 0.28-0.76) were observed in the villages of the east
      coast (mesoendemic stable malaria). The Ab-CS prevalence rates varied from 0 to
      37% in the highlands and southwest region villages (unstable malaria). The use of
      Ab-CS prevalence is proposed to be a useful and reliable seroepidemiologic marker
      of malaria endemicity in those areas of Madagascar in which malaria transmission
      is high and continues for more than four months a year.

PMID- 7810822
TI  - Distribution of hydatidosis and cysticercosis in different Peruvian populations
      as demonstrated by an enzyme-linked immunoelectrotransfer blot (EITB) assay. The
      Cysticercosis Working Group in Peru (CWG).
AB  - A serosurvey for human hydatidosis and cysticercosis was performed in different
      regions of Peru. Those regions included a known endemic area for cystic hydatid
      disease, a cooperative in the central Peruvian Andes near the city of Tarma,
      Department of Junin; three areas endemic for cysticercosis in the Departments of
      Ancash, Cuzco, and San Martin, where the status of hydatid disease is not well
      defined; and an urban shantytown near Lima, where neither zoonosis is known to be
      present. A seroprevalence for hydatidosis 1.9% (6 of 309) was found with both the
      enzyme-linked immunoelectrotransfer blot (EITB) and double diffusion assays in
      the area endemic for hydatidosis. Seroprevalence in the other zones tested was
      zero using only the EITB assay. Cysticercosis seroprevalence was high in pig
      raising zones but low in the high-altitude, sheep-raising areas and in the
      seaport of Callao. No cross-reactions between Echinococcus granulosus and
      cysticercosis were noted in any of the regions studied. Hydatid infection remains
      a major health problem in the central Peruvian Andes where sheep raising is
      widely practiced; however, in those regions where mainly swine are raised, human
      hydatid infection is not a problem.

PMID- 7810824
TI  - Infection, dissemination, transmission, and biological attributes of dengue-2
      PDK53 candidate vaccine virus after oral infection in Aedes aegypti.
AB  - The capacity for oral infection, dissemination, and transmission of the dengue-2
      candidate vaccine virus DEN-2 PDK53 and an isolate from a vaccinate individual,
      DEN-2 Ia8, were compared with the parent strain DEN-2 16681. Capacity for oral
      infection and dissemination to the brain and salivary gland tissues were
      significantly lower in the first two than in the parent strain (P < 0.001).
      Replication was more than 100 times higher for the parent strain when compared
      with the dengue-2 candidate vaccine virus. Transmission was not demonstrated in
      the mosquitoes orally infected with DEN-2 PDK53 and DEN-2 Ia8, whereas
      transmission was achieved in 57% (8 of 14) of mosquitoes infected with the parent
      virus strain. Using immunofluorescence, viral antigen was detected in the
      mosquitoes infected with DEN-2 PDK53 and DEN-2 Ia8. It was seen mainly in the
      form of specks scattered in some parts of the tissues, and was strikingly
      different from that seen in the parent strain, in which major parts of the
      tissues contained viral antigen in the form of rings and specks. The biological
      markers of DEN-2 PDK53 and DEN-2 Ia8 retained the biological characteristic of
      the vaccine after a mosquito passage and a human and mosquito passage,
      respectively.

PMID- 7810827
TI  - [Assessment of elderly with vertigo. Difficulties observed during basic
      examination].

PMID- 7810825
TI  - Etiology of acute diarrhea among United States Embassy personnel and dependents
      in Cairo, Egypt.
AB  - The purpose of this study was to identify the enteropathogens causing acute
      diarrheal disease in Americans living in the North Africa/Middle East region
      during a 34-month period from February 12, 1985 to December 30, 1987 to guide
      preventive and therapeutic measures. Stool specimens were examined and an
      epidemiologic questionnaire was administered to patients with acute diarrhea at
      the Outpatient Health Unit of the United States Embassy in Cairo, Egypt. The
      subjects consisted of 126 American employees and dependents of the U. S. Embassy
      in Cairo, Egypt with diarrhea of less than two-weeks duration. Subjects received
      routine medical care administered by the U.S. Embassy Medical staff. A possible
      etiologic agent was detected in 41% of the subjects. Enteroadherent Escherichia
      coli was the most commonly isolated enteropathogen. A high degree of
      antimicrobial resistance was noted among the bacterial isolates, but all were
      susceptible to the quinolone antibiotics. Episodes of acute diarrhea occurring
      among American expatriates in Cairo, Egypt were primarily of bacterial etiology,
      but only a small portion were caused by the bacterial pathogens routinely
      identified in a standard clinical bacteriology laboratory. Most of the diarrheal
      episodes were due to noninvasive enteroadherent E. coli that may cause prolonged
      disease requiring antimicrobial therapy.

PMID- 7810826
TI  - Evaluation of a twice-a-week application of 1% niclosamide lotion in preventing
      Schistosoma haematobium reinfection.
AB  - A randomized double-blind trial was conducted to assess the efficacy of a twice-a
      week application of 1% niclosamide lotion for prevention of Schistosoma
      haematobium reinfection. Six hundred farmers in Fayoum, Egypt, 18-40 years of
      age, were treated to cure their S. haematobium infection, then randomly assigned
      to self-apply niclosamide or placebo lotion to their limbs, neck, and torso.
      Subjects were exposed to schistosomal-infested water during routine irrigation
      activities from April to October 1992. Three hundred fifty subjects met the
      inclusion criteria and completed the trial, 169 (48.3%) in the niclosamide group
      and 181 (51.7%) in the placebo group. The subjects assigned to the niclosamide
      treated group were comparable with those in the placebo group in age (27.2 versus
      27.8 years), total water contact (101.9 versus 109.0 hr), lotion application
      compliance (93.5% versus 90.6%), and avoidance of whole body water contact (94.7%
      versus 96.7%). The reinfection rate with S. haematobium was 30.8% in the
      niclosamide-treated group and 28.2% in the placebo group. Niclosamide lotion
      applied to the limbs and trunk twice a week failed to prevent S. haematobium
      reinfection.

PMID- 7810828
TI  - [Adenoidectomy and nasal mucociliary transport].
AB  - The paper deals with the research done by the AA. on the nasal mucociliary
      transport-time in a group of 30 children between 3 and 13-year-old. They employ
      the charcoal dust test. The powder is laid inside of the nose the day prior to
      the removal of the adenoids and investigated in the nasopharynx two weeks later.
      The conclusion drawn out is that among these children the mucociliary nasal
      transport time is retarded when compared with other children, turning over to the
      normality two weeks later.

PMID- 7810829
TI  - [Dorsal flap in laboratory animals. Prediction of its viability].
AB  - Various types of flaps were fashioned in the dorsal area of laboratory animals
      (rabbits). Subjective and objective methods were evaluated as means of prediction
      of flap viability: superficial cutaneous temperature and cutaneous fluorescence
      test. It was verified that subjective methods served to help prognosticate flap
      viability, while superficial cutaneous temperature annotations were unreliable as
      indicators. Finally, the cutaneous fluorescence test was revealed to be an ideal
      method of predicting the viability of transferred tissue.

PMID- 7810830
TI  - [Nasal angiofibroma in an adult].
AB  - We have studied a nasal Angiofibroma in a 71-years-old male, who had not
      undergone any male-hormonal-therapy. The age of occurrence and the clinical
      course of this case made the tumor very unlikely to be a silent puberal nasal
      angiofibroma. After morphologic exam and exclusion of other bleeding entities of
      the nasal cavity we arrived at the diagnosis of nasal angiofibroma. We believe
      that this tumor might be arisen "ex novo" and that the nasal angiofibroma of
      elderly people might be a new entity.

PMID- 7810831
TI  - [Bilateral bony choanal atresia in an adult].
AB  - A case of 17-year old male, complaining of long term nasal obstruction is
      presented. Endoscopic nasal exploration showed a bilateral bony choanal atresia,
      confirmed by TC scan. Bilateral choanal atresia in newborns is a life-threatening
      malformation. The urgency management includes, first of all, the establishment of
      a sure orotracheal airway and a delayed surgical correction. A few instances do
      not produce an acute respiratory distress in newborns and failed to be diagnosed
      until nasal obstruction develops other symptoms in adult life.

PMID- 7810832
TI  - [Malherbe's calcifying epithelioma (pilomatrixoma) of the cervical middle line. A
      case report].
AB  - Calcifying epithelioma of Malherbe (Pilomatrixoma) is a rare benign tumor,
      starting in the hair matrix and clinically resembling a hard subcutaneous
      swelling. The most common sites of localization are the head and neck regions.
      Women show a sizeable incidence. We report a case located in the prelaryngeal
      area and emphasize cytodiagnostic by fine needle aspiration. The correct
      treatment consists in pure and simply surgical excision under local anesthesia.

PMID- 7810833
TI  - [Nasal mucociliary transport in normal subjects].
AB  - Clinical study referred to the nasal mucociliary transport of 132 healthy people,
      by means of the charcoal powder method. Intranasal clearance direction of the
      marker, the degree of the test's reproductiveness and the influence on the
      clearance of certain variables are considered. With this procedure the study of
      the nasociliary transportation time become simple, cheap, reliable, reproducible
      and objective. There are great individual variations of the nasal transport-time,
      but it is relatively constant in each examinee. The number of slow markers is
      scarce. The age, the sex, tobacco and the feminine cycle have no influential
      effect in the nasal mucociliary transport-time.

PMID- 7810834
TI  - [Zenker's diverticulum. Four cases].
AB  - The pharyngoesophageal diverticulum (Zenker's diverticulum) is a pathology not
      often found, but it is responsive of dysphagia and other unpleasant ailments
      experienced for the patients, who generally must be submitted to surgery. The AA.
      describe the surgical procedure followed at their ENT-Department at Hospital
      General de Alicante and also some clinic-pathological features verified. Review
      about the literature on the subject. The conclusion drawn out remark the
      feasibility and the effectiveness of this method of diverticulectomy associated
      to the cricopharyngeal myotomy. The dissection is easied introducing strips of
      gauze into the diverticular sack and retaining the oesophagoscope inside the
      organ during the procedure.

PMID- 7810836
TI  - [Embryonic death. Maternal recognition of pregnancy].

PMID- 7810835
TI  - [Tuberculosis of the pharynx].
AB  - Report of two cases of pharyngeal tuberculosis, both patients showing clinical
      lesions consistent with tonsillar neoplasia. Comments remarking some features
      regarding its pathogenesis, considerations on the value of diagnostic tests,
      particularly the baciloscopy, Mantoux-test, and histology, as well as
      therapeutics considerations.

PMID- 7810837
TI  - [Markers in the evolution and control of HIV infection].

PMID- 7810838
TI  - [Apoptosis in HIV infection].

PMID- 7810839
TI  - [The conservative surgery of breast cancer after 17 years of experience].

PMID- 7810840
TI  - [The physiology of the hypothalamo-hypophyseal axis].

PMID- 7810841
TI  - [Are left-handed people "sinister"?].

PMID- 7810842
TI  - [Devices and drugs introduced intraocularly for the treatment of eye diseases "in
      the office"].

PMID- 7810843
TI  - [The Big Bang versus the continuous creation of matter].

PMID- 7810844
TI  - [The burning mirror, a symbol of the Academia de Medicina?].

PMID- 7810845
TI  - Prevention across the life span: healthy people for the twenty-first century.

PMID- 7810846
TI  - Prevention across the life span: healthy people for the twenty-first century.

PMID- 7810847
TI  - Prevention across the life span: healthy people for the twenty-first century.

PMID- 7810848
TI  - Prevention across the life span: healthy people for the twenty-first century.

PMID- 7810850
TI  - Prevention made visible for the future.

PMID- 7810849
TI  - The economics of prevention.

PMID- 7810851
TI  - Sociocultural perspective of prevention.

PMID- 7810852
TI  - Establishing community coalitions for prevention: Healthy Cities Indiana.

PMID- 7810853
TI  - Prevention: maternal and infant health.

PMID- 7810854
TI  - Prevention: child health.

PMID- 7810855
TI  - Prevention: adolescent health.

PMID- 7810856
TI  - Prevention: adults with chronic disease.

PMID- 7810857
TI  - Prevention: work site wellness.

PMID- 7810858
TI  - Prevention: older adults.

PMID- 7810859
TI  - Research applications in prevention.

PMID- 7810860
TI  - Health promotion: public policy goal.

PMID- 7810861
TI  - Modification of cysteine residues with N-methyl iodoacetamide.
AB  - Cysteine residues derivatized with N-methyl iodoacetamide (MIAA) can be analyzed
      by the Edman sequencing with a high degree of reliability. By HPLC, the
      phenylthiohydantoin (PTH) derivative of MIAA-modified cysteine eluted between
      dimethylphenylthiourea and PTH-Ala--a wide gap which is not occupied or
      interfered with by any other by-products or PTH amino acids. During extended
      Edman degradation, the recovery of PTH derivative of MIAA-modified Cys was as
      quantitative and reproducible as that of other stable PTH derivatives such as
      Ala, Val, and Leu.

PMID- 7810862
TI  - A method to increase efficiency and minimize anomalous electrophoretic transfer
      in protein blotting.
AB  - We find that in protein blotting, the electrophoretic transfer efficiency of a
      given protein can be markedly affected by other components in the sample. Using a
      variety of electrophoretic elution protocols, we obtained very inefficient
      transfer of purified 125I-labeled 275-kDa cation-independent mannose 6-phosphate
      receptor from a sodium dodecyl sulfate-polyacrylamide gel to a membrane.
      Surprisingly, the transfer efficiency increased significantly if other proteins
      that migrated in the vicinity of the receptor were present. This may be a
      generally unappreciated but potentially widespread phenomenon as other but not
      all radiolabeled proteins examined behaved similarly. This carrier effect occurs
      under conditions typically used in protein blotting experiments and can lead to
      large errors in quantitative analysis. We developed two methods to minimize the
      carrier effect. First, addition of excess carrier protein to samples prior to
      electrophoresis saturated the carrier effect so that different samples had
      similar transfer efficiencies. Second, addition of either bovine serum albumin or
      sodium deoxycholate to the cathodic electro-elution buffer markedly increased
      transfer efficiency of radiolabeled proteins that exhibited poor transfer
      efficiency and minimized transfer differences between samples that contained or
      lacked carrier. These methods should be generally applicable to standard protein
      blotting and analysis protocols.

PMID- 7810863
TI  - Long-term measurement of organ copper turnover in rats by continuous feeding of a
      stable isotope.
AB  - Utilizing the continuous feeding of a single stable isotope and inductively
      coupled plasma mass spectrometry, we have developed a method that allows the
      measurement of organ copper turnover in the rat for at least 8 weeks. Previous
      methods, based on tracer studies using radioisotopes of copper, were severely
      limited by the short half-lives of the radioisotopes (12.8 and 61.8 h). Taking
      advantage of the known ratio of the two naturally occurring stable isotopes of
      copper (63Cu and 65Cu), dietary copper was replaced by a single isotope of copper
      (63Cu) for the entire 8-week period. Disappearance of the other isotope (65Cu)
      from tissues was then monitored as a measure of copper turnover. Because this
      method is not a tracer study, it has the unique advantage of uniformly labeled
      physiological and kinetic compartments. Half-lives of individual first-order
      kinetic compartments within organs and plasma were obtained by analysis of the 8
      week copper turnover curves in copper-adequate and copper-restricted rats. Mean
      decreases in organ copper following 56 days of copper restriction were plasma,
      99%; liver, 62%; heart, 3%; muscle, 26%; kidney, 66%; and brain, < 1%. Comparison
      of normal organ turnover to turnover in copper-restricted rats revealed that this
      method can be used during periods of severe copper restriction and that copper
      conservation during these periods is organ specific.

PMID- 7810864
TI  - An instrument for the measurement of rapid reaction kinetics.
AB  - Two versions of an inexpensive mixing device capable of measuring reaction
      kinetics with millisecond resolution are described. The instruments deliver
      reactants via microsyringes controlled by nitrogen pressure at time intervals
      that are either mechanically or software controlled. In addition, an optical
      system for calibration of the time required to deliver the reactants as well as
      the intervals between syringe firing is given. Data illustrating the effect of
      variations in volume and syringe size on the accuracy and reproducibility of
      these time measurements as well as the volume of fluid delivered are presented.
      Examples of kinetic measurements of several reactions illustrating the
      capabilities of the instrument are also presented.

PMID- 7810865
TI  - The biotin/avidin-mediated microtiter plate lectin assay with the use of
      chemically modified glycoprotein ligand.
AB  - The conditions of a simple and sensitive microtiter plate lectin assay with
      biotinylated TF- and/or Tn-reactive lectins and ExtrAvidin/alkaline phosphatase
      conjugate are described. As ligand for lectin binding, chemically modified
      glycophorin A from human erythrocytes was used. The TF and Tn receptors present
      in glycophorin A in cryptic form were exposed by desialylation under mild acidic
      conditions (TF) and by removing galactose residues from asialoglycophorin by
      Smith degradation (Tn). These modifications can be performed either in solution
      or on the plate coated with untreated glycophorin. It was demonstrated with six
      lectins that their biotinylation via lectin amino groups gave products of higher
      binding activity than biotinylation via periodate-oxidized carbohydrate residues
      of lectins. The first step in the binding assay requires the selection of the
      proper concentration of the glycoprotein used for coating the plate, since the
      lectins tested showed a maximal binding at an optimal glycophorin concentration,
      and in many cases the binding was distinctly lower when a higher ligand
      concentration was used for coating. The inhibition of binding of Tn-reactive
      lectins to plates coated with asialo-agalactoglycophorin (Tn antigen) was
      performed using low- and high-molecular-weight inhibitors (1-2 micrograms lectin
      was used for each inhibition curve) and concentrations of inhibitors required for
      50% inhibition of lectin binding were compared. The results were in agreement
      with the known specificity of the lectins tested. In conclusion, the method
      described is simple, sensitive, and versatile, enabling the characterization of
      lectin specificity with a broad spectrum of inhibitors using microgram quantities
      of lectin only.

PMID- 7810866
TI  - A method of preparation and purification of (4R)-deuterated-reduced nicotinamide
      adenine dinucleotide phosphate.
AB  - (4R)-Deuterated-reduced nicotinamide adenine dinucleotide phosphate, (4R)
      [2H]NADPH, was prepared by reduction of NADP+ using an NADP(+)-dependent alcohol
      dehydrogenase (EC 1.1.1.2) from Thermoanaerobium brockii and isopropanol-d8 as
      substrate at 43 degrees C, pH 9. More than 80% of the product was identified as
      reduced cofactor by reverse-phase (ODS) HPLC, and a 1H NMR study showed that all
      of the reduced cofactor was (4R)-deuterated. Less than 10% of the product was
      oxidized cofactor, the remainder being impurities from the breakdown of the
      dinucleotide compound. Subsequent purification carried out by semipreparative
      reverse-phase HPLC with 0.1 M NaCl at pH 8.5 gave a compound of more than 96%
      purity. Separated (4R)-[2H]NADPH fractions were freeze-dried and the white solid
      was stored at 5 degrees C with desiccant.

PMID- 7810868
TI  - Comparison of the separation of proteins by sodium dodecyl sulfate-slab gel
      electrophoresis and capillary sodium dodecyl sulfate-gel electrophoresis.
AB  - Capillary sodium dodecyl sulfate-gel electrophoresis, a one-dimensional version
      of the well-established planar analytical method of SDS-polyacrylamide gel
      electrophoresis, has proven a powerful new microanalytical method for the
      separation of protein molecules according to their size. In this paper the planar
      SDS-PAGE and the capillary SDS-gel electrophoresis of different proteins are
      compared with respect to performance, precision, and efficiency. Molecular weight
      versus migration distance and migration time curves for 65 proteins, running from
      14,200 to 205,000 Da, are given for both methods.

PMID- 7810867
TI  - Quantitation of tryptophan and tyrosine residues in proteins by fourth-derivative
      spectroscopy.
AB  - A method for quantitation of tryptophan and tyrosine residues in proteins by
      fourth-derivative ultraviolet spectroscopy is described. The direct quantitation
      of tryptophan is based on measurement of a tryptophan-specific trough at 292 nm
      in the fourth derivative of a protein's ultraviolet absorption spectrum. A peak
      overlapping the tryptophan and tyrosine signatures at A282 is used to quantify
      tyrosine content. The procedure is accomplished by adding back known quantities
      of tyrosine to the sample and subtracting the contribution of tryptophan to the
      A282 peak to obtain an internal calibration curve. This curve is linear, with the
      ordinate axis intercept relating the quantity (residues/mole) of tyrosine present
      in the protein. This nondestructive and facile method was used to successfully
      predict the tryptophan and tyrosine content of a variety of well-characterized
      proteins. The utility of this method was further demonstrated by resolving the
      number of tryptophan and tyrosine residues in proteins oxidized by N
      bromosuccinimide.

PMID- 7810869
TI  - Spectrophotometric determination of dehydroascorbic acid in biological samples.
AB  - We describe a method for accurately and precisely measuring dehydroascorbic acid
      in perchloric acid extracts prepared from human plasma, lymphocytes, and
      mammalian cells. Samples were assayed by spectrophotometrically monitoring the
      kinetics of the concentration-dependent absorbance changes of dehydroascorbic
      acid with phosphate-methanol-containing buffers. The lowest detectable
      dehydroascorbate concentration using this assay is estimated to be below 0.1
      mumol/liter. Total analysis time is less than 10 min and allows the simultaneous
      measurement of numerous samples. The calibration curve is linear (r > 0.995) over
      the range 0-200 mumol/liter. The dehydroascorbic acid concentrations measured in
      supplemented samples agree with known concentrations. Interference of ascorbic
      acid and 2,3-diketogulonic acid with this assay was excluded. The correlation
      with a highly specific chromatographic procedure gave comparable results over the
      range of physiologically relevant concentrations. The procedure avoids the most
      commonly applied method of measuring the native ascorbic acid, then reducing the
      dehydroascorbic acid, and finally measuring the total ascorbic acid and
      determining dehydroascorbic acid by the difference. Stabilization of ascorbic
      acid during assay was achieved by addition of desferrioxamine.

PMID- 7810870
TI  - High-field deuterium nuclear magnetic resonance spectroscopic monitoring of the
      pharmacokinetics of selectively deuterated benzoic acid in man.
AB  - The stable isotope tracer technique using 13C labeling of substrates followed by
      NMR spectroscopy of biofluids has been widely used in metabolic investigations,
      whereas the use of 2H labeling and 2H NMR spectroscopy has been extremely
      limited. The applicability of the high-field 2H NMR spectroscopy (14.1 T, 92 MHz
      2H frequency) in a simple pharmacokinetic problem has now been investigated using
      selectively deuterated benzoic acid (BA) as a model. [7-13C,2,6-2H2]BA was
      synthesized for use as a tracer to compare the efficiency and sensitivity of 2H
      and 13C labeling. The urinary excretion of [7-13C,2,6-2H2]hippuric acid (HA)
      formed from orally administered [7-13C,2,6-2H2]BA (250 mg) was followed by 92-MHz
      2H and 150-MHz 13C NMR spectroscopy (only 10 min accumulation time) following
      concentration of urine by a factor of 10, using a standard for quantitation. The
      heights of resonances for 13C7 and 2H2,6 were used to calculate the [7-13C,2,6
      2H2]HA concentration. The lower limit of detection using this 2H NMR approach was
      approximately 60 nmol/ml and was found to be comparable with that of the 13C NMR
      approach where the quaternary carbon (C7) was labeled. The administered [7
      13C,2,6-2H2]BA was found to be quantitatively biotransformed to HA and excreted
      in urine within 4 h by both NMR approaches. The 2H NMR approach using a high
      field NMR spectrometer is potentially useful and practical for pharmacokinetic
      research on small molecules whose 2H resonances are relatively sharp since the
      procedures are very simple and convenient.

PMID- 7810871
TI  - Assay of DNA denaturation by polymerase chain reaction-driven fluorescent label
      incorporation and fluorescence resonance energy transfer.
AB  - We have developed a simple and sensitive assay method to monitor DNA
      denaturation. This method is based on (i) incorporation of fluorescent labels
      onto complementary DNA strands during target-specific amplification by polymerase
      chain reaction and (ii) detection of DNA denaturation by fluorescence resonance
      energy transfer. Fluorescein-11-dUTP and rhodamine-4-dUTP were used to label
      complementary DNA strands as the energy transfer donors and acceptors,
      respectively. The complementary DNA strands thus labeled were then annealed by
      incubation at a constant temperature, and the energy transfer efficiency was
      monitored during DNA denaturation experiments. Both heat denaturation and alkali
      denaturation could be monitored by this assay. Some factors affecting the DNA
      denaturation were also investigated.

PMID- 7810872
TI  - Blotting of glycolipids and phospholipids from a high-performance thin-layer
      chromatogram to a polyvinylidene difluoride membrane.
AB  - A simple method of blotting glycosphingolipids from a high-performance thin-layer
      chromatography (HPTLC) plate to a polyvinylidene difluoride (PVDF) membrane is
      described. The developed HPTLC plate is dipped in a solvent mixture
      (isopropanol/0.2% CaCl2/methanol, 40/20/7 by volume) for blotting, after which
      first a PVDF membrane and then a glass microfiber filter is placed on the plate.
      The assemblage then is pressed for 30 s with heating. Most of the
      glycosphingolipids that are separated on the HPTLC plate can be blotted
      quantitatively and detected with the reagents used on the plate. Detection of the
      glycosphingolipids on the membrane was confirmed to be more sensitive than that
      on the HPTLC plate by both chemical visualization and immunological staining. The
      glycosphingolipids blotted on the membrane could be reextracted. Blotting of
      phospholipids can be done by the same method. The results suggest that this
      method can be used in the purification and characterization of glycosphingolipids
      and in the detection of proteins which recognize glycosphingolipids and
      phospholipids.

PMID- 7810875
TI  - A straightforward method for purification of myo-inositol 1,3,4,5,6
      pentakisphosphate from avian erythrocytes for subsequent application in studies
      on hemoglobin allosteric effect.
AB  - myo-Inositol 1,3,4,5,6-pentakisphosphate (Ins-P5) is the main allosteric effector
      of hemoglobin in avian erythrocytes. Molecular studies on the functioning of
      hemoglobin have frequently been performed with the hexaphosphate form of
      inositol, since it is difficult to obtain Ins-P5 of appropriate purity and in
      sufficient quantity for oxygen-affinity studies. This paper provides a detailed
      description of a method for adequate isolation of Ins-P5 from avian erythrocytes.
      The method is based on fractionation of erythrocyte organic phosphates by
      chromatography. The fractions corresponding to the peak of Ins-P5 were retained
      for further purification and concentration. This process includes gel filtration,
      cation-exchange chromatography, and lyophilization. At the end of the process
      about 15 mg of Ins-P5, free from other organic phosphates or salts, was obtained
      from 45 ml of pigeon blood. Trials performed on avian stripped hemoglobin
      solutions with Ins-P5 obtained in this way confirm that this phosphate is the
      main factor responsible for the decrease in oxygen affinity in intact
      erythrocytes, and that it is preferable to Ins-P6 for hemoglobin oxygen-affinity
      studies.

PMID- 7810874
TI  - Synthesis and characterization of a bioluminogenic substrate for alpha
      chymotrypsin.
AB  - 6-(N-Acetyl-L-phenylalanyl)-aminoluciferin as an example for a new class of
      highly sensitive bioluminogenic substrates that has been synthesized and
      characterized. These peptide derivatives can be used regarding to the peptide
      residue as highly sensitive substrates for different proteinases. Here we
      demonstrate the use of 6-(N-acetyl-L-phenylalanyl)-aminoluciferin as a novel
      bioluminogenic substrate for alpha-chymotrypsin. The kinetic parameters
      determined for 6-(N-acetyl-L-phenylalanyl)-aminoluciferin are Km = 0.38
      mmol/liter, kcat = 6.5 s-1, and kcat/Km = 17,100 (liter/mol.s). The test
      principle of the coupled bioluminogenic assay is the release of aminoluciferin by
      enzymatic cleavage of 6-(N-acetyl-L-phenylalanyl)-aminoluciferin. Aminoluciferin
      is a very sensitive substrate of firefly luciferase and can be easily quantified
      in a luminometric assay. Amounts of chymotrypsin down to 0.3 ng per assay can be
      routinely determined.

PMID- 7810873
TI  - Assay of the enantiomers of 1,2-propanediol, 1,3-butanediol, 1,3-pentanediol, and
      the corresponding hydroxyacids by gas chromatography-mass spectrometry.
AB  - We developed gas chromatographic-mass spectrometric assays for the enantiomers of
      1,2-propanediol, 1,3-butanediol, 1,3-pentanediol, and their corresponding
      hydroxyacids, lactate, beta-hydroxybutyrate, and beta-hydroxypentanoate (3
      hydroxyvalerate) in biological fluids. The corresponding ketoacids, acetoacetate
      and beta-ketopentanoate, can be assayed simultaneously by pretreating the samples
      with NaB2H4. The assays involve spiking the samples with deuterated internal
      standards, deproteinization, ether extraction, and derivatization of the carboxyl
      groups with (R,S)-2-butanol/HCl and of the hydroxyl groups with chiral (S)-(+)-2
      phenylbutyryl chloride. Mass spectrometric analysis is conducted under ammonia
      positive chemical ionization. We used these assays to follow the metabolism of
      diol enantiomers in dogs. For (R,S)-1,3-butanediol and (R,S)-1,3-pentanediol, the
      uptakes from dog plasma of the R and S enantiomer of each diol were identical. In
      contrast, the metabolism of (S)-1,2-propanediol was faster than that of (R)-1,2
      propanediol. (R)-1,2-Propanediol is formed during acetone metabolism, while (R,S)
      1,3-butanediol and (R,S)-1,3-pentanediol are potential nutrients. The assays
      developed will allow further investigations of the metabolisms of acetone, (R)
      lactate, and artificial nutrients derived from the 1,3-butanediol and 1,3
      pentanediol enantiomers.

PMID- 7810877
TI  - A continuous spectrophotometric method for the determination of glycogen
      phosphorylase-catalyzed reaction in the direction of glycogen synthesis.
AB  - We offer a "continuous" spectrophotometric method for the determination of the
      glycogen phosphorylase-catalyzed reaction in the direction of glycogen synthesis.
      This method relies on a coupled enzyme procedure, involving purine nucleoside
      phosphorylase and its chromophoric substrate, 2-amino-6-mercapto-7-methyl
      ribonucleoside (7-methyl-6-thioguanosine (MTGuo)), for the estimation of
      inorganic phosphate (M. R. Webb, Proc. Natl. Acad. Sci. USA 89, 4884-4887, 1992).
      We have examined the effects of the reaction components on the catalytic
      activities of both "primary" and "coupling" enzymes. While MTGuo exhibits no
      effect on the glycogen phosphorylase-catalyzed reaction, glucose 1-phosphate and
      AMP are partially inhibitory to nucleoside phosphorylase. However, the latter
      effects pose no problem as long as the coupling enzyme is maintained at a
      relatively higher concentration in the assay system. The coupled enzyme assay
      system, standardized for the measurement of glycogen phosphorlase activity, has
      enabled us to demonstrate explicitly that the rate of the enzyme-catalyzed
      reaction exhibits sigmoidal dependence on both AMP and glucose 1-phosphate
      concentrations. We argue that these sigmoidal profiles have been observed due to
      the sensitivity and precision of the present assay system.

PMID- 7810876
TI  - Homogeneous fluorescence detection method for human leukocyte antigen-DR typing
      following polymerase chain reaction amplification with sequence-specific primer.
AB  - A fluorescent homogeneous method for the detection of sequence-specific
      amplification of human leukocyte antigen (HLA) alleles has been developed. In
      this approach, polymerase chain reaction sequence-specific primers (PCR-SSP) are
      used to amplify DRB1, DRB3, and DRB4 alleles. Lambda exonuclease and Exonuclease
      I are added to reduce background by digesting template DNA, partial primer dimer,
      and primer. PCR amplicons are then detected following the addition of a
      fluorescent dye (thiazole yellow dimer) which binds to double-stranded DNA. No
      transfer or wash steps are required. Thus, the risk of sample contamination,
      which is a major source of inaccuracy for DNA amplification methods, is greatly
      reduced. This approach is also faster and more easily automated than the standard
      approach using gel electrophoresis and ethidium bromide staining. Speed and
      automation are important considerations for HLA typing since the number of
      possible alleles for each HLA type is substantial. A homogeneous HLA-SSP typing
      method may be especially useful for clinical labs doing large numbers of samples
      and for the eventual automation of HLA DNA typing.

PMID- 7810878
TI  - A sensitive assay of acyl-coenzyme A oxidase by coupling with beta-oxidation
      multienzyme complex.
AB  - A highly sensitive and reliable method for assaying acyl-CoA oxidase (EC
      1.3.99.3) activity was developed. An acyl-CoA oxidase-dependent [1-14C]palmitoyl
      CoA degradation to acetyl-CoA, acid-soluble products, was measured by coupling
      with the multienzyme complex for fatty acid oxidation from Pseudomonas fragi. The
      activity, more than 2 pmol/min, could be assessed using this method. The activity
      was dependent on the coupling enzyme (multienzyme complex), coenzymes such as
      NAD+ and CoA, and oxygen, and the interference of acyl-CoA dehydrogenases was
      excluded. The activity in human samples of cultured skin fibroblasts and
      lymphocytes was compatible with the expected activity calculated from the amount
      of acyl-CoA oxidase protein estimated by immunoblot analysis. The method which
      was verified in several experiments can be used for clinical diagnosis of acyl
      CoA oxidase deficiency and for determination of activity in samples with a low
      level of acyl-CoA oxidase.

PMID- 7810879
TI  - Assay of the concentration and 13C-labeling pattern of phenylacetylglutamine by
      nuclear magnetic resonance.
AB  - Phenylacetate, derived from phenylalanine, is converted in human and primate
      liver to phenylacetylglutamine. The latter, which is excreted in urine, has been
      used to probe noninvasively the labeling pattern of liver citric acid cycle
      intermediates. We present nuclear magnetic resonance assays for the urinary
      concentration of phenylacetylglutamine and for the 13C-labeling pattern of its
      glutamine moiety. The concentration of phenylacetylglutamine is calculated from
      the natural 13C signals of all carbons of its benzene ring and C-2 of its acetyl
      moiety. The limit of detection is 13 mumol of unlabeled phenylacetylglutamine.
      The minimum amount of phenylacetylglutamine needed to determine a 1% enrichment
      of one of its carbons is 26 mumol. The technique was tested by analyzing
      phenylacetylglutamine in the urine from monkeys infused with various 13C tracers.
      The labeling patterns obtained agreed with theoretical calculations and patterns
      reported in phenylacetylglutamine and glutamine labeled from 14C and 13C tracers,
      respectively.

PMID- 7810880
TI  - On-line procedures for alkylation of cysteine residues with 3-bromopropylamine
      prior to protein sequence analysis.
AB  - We have previously shown that 3-bromopropylamine offers several advantages over
      other alkylating reagents in the modification and subsequent identification of
      cysteine residues by protein sequencing. We describe here simple on-sequencer
      procedures for alkylating cysteines in proteins which employ the reduction of
      cystines in proteins with tri-n-butylphosphine and concomitant alkylation of the
      resulting cysteines with 3-bromopropylamine. Addition of an aqueous acetone wash
      to a modified reaction cycle on the Applied Biosystems 477A sequencer removes
      excess 3-bromopropylamine. As a result, very little background in the first step
      of the sequence analysis is seen. Under these conditions, cysteines are readily
      modified and identified during sequencing. Moreover, very little preview of the
      next amino acid is observed, which indicates that the N-terminal amino acid is
      not appreciably alkylated by 3-bromopropylamine. On-sequencer methods have been
      developed for proteins spotted onto glass fiber filters and proteins
      electroblotted onto polyvinylidene difluoride membranes.

PMID- 7810881
TI  - A continuous, spectrophotometric activity assay for nitrogenase using the
      reductant titanium(III) citrate.
AB  - A continuous, spectrophotometric assay for determining electron transfer rates
      through nitrogenase during substrate reduction reactions was developed. The assay
      takes advantage of the facts that Ti(III) citrate can serve as a reductant for
      nitrogenase-catalyzed reduction reactions and that oxidation of Ti(III) citrate
      to Ti(IV) citrate results in a dramatic change in its absorption spectrum.
      Ti(III) citrate supported nitrogenase-catalyzed substrate (e.g., H+ or acetylene)
      reduction reactions at about the same rate as that supported by the reductant
      dithionite (S2O4(2-)). In addition, Ti(III) citrate had an absorption maximum
      centered at 325 nm, while oxidized Ti(IV) citrate had a much lower absorption in
      this wavelength region. An absorption coefficient for Ti(III) citrate of 0.73 mM
      1.cm-1 at 340 nm was determined by titration with redox dyes with known
      absorption coefficients. Using this experimentally determined absorption
      coefficient, we developed an assay that provides a convenient way to determine
      electron transfer rates through nitrogenase in real time by
      spectrophotometrically following the oxidation of Ti(III) citrate to Ti(IV)
      citrate. Average electron transfer rates of 3749 +/- 218 nmol of electrons
      transferred.min-1.mg iron protein-1 for H+ reduction were determined using this
      assay which are directly comparable to the rates calculated from fixed time
      point, gas chromatographic assays of H2 formation. The utility of the Ti(III)
      citrate assay for nitrogenase is discussed and demonstrated using the nitrogenase
      inhibitors MgADP, CN-, and NO.

PMID- 7810882
TI  - Nonradioactive receptor binding assay for ciliary neurotrophic factor.
AB  - A nonradioactive receptor binding assay for ciliary neurotrophic factor (CNTF) is
      described. The assay is based on the interaction between biotinylated human CNTF,
      soluble gp130, and soluble myc-tagged CNTF receptor captured on a microtiter
      plate via an antibody against the myc epitope tag. Bound cytokine is revealed by
      alkaline phosphatase-conjugated avidin. Purified human and rat CNTF competed with
      biotinylated CNTF for receptor binding, with IC50 values of 29 and 2 nM,
      respectively. Since the higher affinity of rat vs human CNTF has been previously
      shown to be conferred by the arginine residue at position 63 of the rat protein,
      we also tested a human CNTF mutant carrying a Q63R substitution. Secreted forms
      of wild-type and mutant CNTF were expressed in Escherichia coli, and the amount
      of cytokines in periplasmic extracts was determined by quantitative Western
      blotting analysis. The human CNTF mutant (Q63R, N137S) was found to compete with
      biotinylated CNTF for binding to soluble CNTF receptor with an eightfold higher
      apparent affinity than wild-type human CNTF. The present method thus faithfully
      reproduces the relative activities of CNTF analogs determined in other assay
      systems. The possibility of assaying cytokines in crude bacterial extracts makes
      the new technique particularly suitable for rapidly determining the receptor
      binding potencies of genetically engineered CNTF variants.

PMID- 7810883
TI  - Tetracyanoquinodimethane-mediated flow injection analysis electrochemical sensor
      for NADH coupled with dehydrogenase enzymes.
AB  - A flow injection analysis (FIA) sensor for the oxidation of NADH is reported. The
      system utilizes a graphite paste electrode modified with the electroactive
      material tetracyanoquinodimethane (TCNQ). TCNQ acts as an efficient mediator for
      the oxidation of NADH to biologically active NAD+. Alcohol dehydrogenase/lactate
      dehydrogenase and NAD+ were coimmobilized in TCNQ-modified graphite paste using
      polyethylenimine to develop a FIA sensor for ethanol/lactate. The system
      responded rapidly with wide linearity. Response curves for ethanol/lactate and
      NADH are reported.

PMID- 7810884
TI  - A syringe-based gradient former for linear and exponential gradients.
AB  - This report describes a reliable and inexpensive gradient former constructed from
      disposable plastic syringes. The dual-chamber device produces both linear and
      exponential gradients which are very reproducible and essentially identical to
      the theoretical curve. Two identical syringes which serve as a mixing chamber and
      reservoir chamber are heat sealed at the bottom and glued to a flat plastic
      support plate. Small holes are drilled into the side walls of the syringes to
      accommodate an outlet tube and mixing tube. To form linear gradients, equal
      volumes of solution are placed in both chambers. The solution in the mixing
      chamber is stirred with a small magnetic stir bar. As starting solution is drawn
      from the mixing chamber, ending solution is gradually drawn into the mixing
      chamber to produce a linear gradient. To form exponential gradients a syringe
      plunger is placed into the mixing chamber to form a fixed volume of starting
      solution. Ending solution is placed into the reservoir chamber and may be
      replenished at any time during gradient formation. This allows small gradient
      formers to produce large volume exponential gradients. These gradient formers,
      which require only about 10 min to construct, are durable enough to be used many
      times and inexpensive enough to discard if desired.

PMID- 7810885
TI  - Radioassay of bifunctional 5-aminoimidazole-4-carboxamide ribotide transformylase
      IMP cyclohydrolase by thin-layer chromatography.
AB  - A radioassay has been developed for the bifunctional enzyme, AICAR transformylase
      IMP cyclohydrolase, which catalyzes reactions 9 and 10 of the de novo pathway for
      biosynthesis of purine nucleotides (AICAR-->FAICAR-->IMP). 3H-labeled AICAR or
      FAICAR is converted enzymically to product(s) which are separated by one
      dimensional thin-layer chromatography prior to quantification by scintillation
      counting. Using this sensitive radioassay, a dissociation constant of IMP
      cyclohydrolase for FAICAR of 0.87 microM has been determined and AICAR, FAICAR,
      and IMP can be quantified in assay mixtures for AICAR transformylase-IMP
      cyclohydrolase. The ratio of specific enzymic activities for AICAR
      transformylase:IMP cyclohydrolase is 1:44.

PMID- 7810886
TI  - Quantification of oxidized metallothionein in biological material by a Cd
      saturation method.
AB  - A rapid and easy to perform method for determining oxidized metallothionein (MT)
      is described. The main features of the procedure are that oxidized MT is
      converted into native MT with 2-mercaptoethanol as reducing agent and Zn2+ as
      metal donor, and MT is subsequently quantified via Cd saturation. The procedure
      was effective in recovering MT oxidized either by Cu2+ or by neutralization of
      apothionein at pH 3, independent of the amount of MT, the origin of sample,
      degree of oxidation, and oxidation method. As demonstrated by HPLC analysis, the
      method is highly specific for MT. The described procedure provides information on
      both the total concentration of MT independent of its thiol redox state and the
      metal binding capacity of the protein; thus, it is of particular interest in
      studying the role of MT in metal metabolism and toxicity.

PMID- 7810888
TI  - A comparison of different promoter, enhancer, and cell type combinations in
      transient transfections.

PMID- 7810887
TI  - An octaethylene glycol monododecyl ether-based mixed micellar assay for
      lipoxygenase acting at neutral pH.
AB  - Using the detergent octaethylene glycol monododecyl ether (C12E8), a
      spectrophotometric mixed micellar assay for lipoxygenas (LOX) activity was
      designed. Potato LOX was able to use the linoleic acid (LA) solubilized in C12E8
      micelles, displaying the characteristic induction period of LOX-catalyzed LA
      peroxidation. In the mixed micellar system, LOX responds to the LA surface
      concentration expressed as mol% (=[lipid]*100/([detergent]-cmc)) and not to the
      molarity of the LA. For both potato and soybean LOX, Vmax was independent of the
      mixed micelle concentration, while Km was independent as well when expressed as
      mol% but was dependent on C12E8 concentration when expressed in molar. In mixed
      micelles, H2O2 shortened the induction period, while 13-hydroperoxylinoleic acid
      and t-butyl hydroperoxide completely removed it. C12E8/LA proved to be a reliable
      system for assaying LOX activity at pH values around neutrality. Like Tween 20,
      this system avoided the turbidity problems arising from the protonated fatty acid
      and did not interfere with the uv-absorption band of the hydroperoxide product.
      However, this system is superior to the commonly used Tween 20 because it permits
      investigation of the lipid requirements of LOX since the concentration
      independent Km can be determined both in mol% and as the absolute number of
      lipids per micelle. In addition, the detergent did not affect the enzyme through
      any side effects.

PMID- 7810889
TI  - One-step protein purification using micropreparative electrophoresis fully
      compatible with protein microsequencing.

PMID- 7810890
TI  - Indirect introduction of long-chain pyrene-phosphatidylcholine into living cells.

PMID- 7810891
TI  - Separation of neuropeptides by inverse gradient reversed-phase liquid
      chromatography on a bonded phenyl support.

PMID- 7810892
TI  - Generation of multiple mutations in the same sequence via the polymerase chain
      reaction using a single selection primer.

PMID- 7810893
TI  - Quantitation of soluble superoxide dismutase in rat striata, based on the
      inhibition of nitrite formation from hydroxylammonium chloride.

PMID- 7810894
TI  - Quantitating apoptosis by a nonradioactive DNA dot blot assay.

PMID- 7810895
TI  - Analysis of double-stranded oligonucleotides by electrospray mass spectrometry.
AB  - Double-stranded oligonucleotides of different lengths and chemical modification
      have been analyzed by ion spray mass spectrometry. The non-covalent-bonded
      duplexes can be detected. Therefore, ion spray mass spectrometry is a useful
      method for investigation of hybridizations of natural and chemically modified
      oligonucleotides. Since the exact mass of the double strand can be detected, this
      method can distinguish between specific and nonspecific interaction.

PMID- 7810896
TI  - In vitro and in vivo performance and lifetime of perfluorinated ionomer-coated
      glucose sensors after high-temperature curing.
AB  - In this paper we report that curing at 120 degrees C can be used to improve the
      in vivo durability of a miniaturized glucose sensor with an outer coating of the
      Dupont perfluorinated ionomer, Nafion. Sensors based on glucose oxidase trapped
      in an albumin/glutaraldehyde matrix were able to withstand curing at 120 degrees
      C without noticeable change in electrode sensitivity (+/- 22% SD). Curing above
      120 degrees C caused a gradual decline in sensitivity, with no sensitivity seen
      at 170 degrees C. Curing Nafion at 120 degrees C eliminated ascorbic acid and
      urea interferences and improved selectivity for glucose against uric acid and
      acetaminophen, compared to room temperature-cured Nafion coatings. The Nafion
      film reduced O2 demand by the sensor, so the signal was O2 independent across a
      partial pressure range of 8-140 mmHg. Several of the fully assembled, heat-cured,
      needle-type glucose sensors remained functional for at least 10 days after
      subcutaneous implantation in dogs, without degradation of their sensitivity
      (average 3 nA/mM in vivo at 37 degrees C and 6 nA/mM in vitro at 37 degrees C).

PMID- 7810897
TI  - Multilabeling of ferrocenes to a glucose oxidase-digoxin conjugate for the
      development of a homogeneous electroenzymatic immunoassay.
AB  - A new homogeneous electroenzymatic immunoassay was developed to determine
      antibody concentration using glucose oxidase and ferrocene as enzymatic and
      electrochemical amplifier, respectively. Digoxin (Dig)-conjugated glucose oxidase
      (GOx) was modified with ferrocene (Fec) to form Fec-GOx-Dig conjugate. After
      immunocomplex formation between the Fec-GOx-Dig conjugate and the anti-digoxin
      antibody, the complex underwent less electrochemical reaction due to the steric
      hindrance of the antibody. The ferrocene multilabeled conjugate was provided for
      the determination of anti-digoxin antibody. Since the strategy taken here is
      based on a combined effect of GOx and ferrocene, i.e., enzymatic amplification by
      GOx and electrochemical amplification by multilabeled ferrocenes, the antibody
      concentration was determined in the range from 1/50 to 1/500 dilution.

PMID- 7810898
TI  - Metal speciation by supercritical fluid extraction with on-line detection by
      atomic absorption spectrometry.
AB  - A silica flame-in-tube interface is described for the sensitive detection, by
      AAS, of As, Cd, Cu, Mn, Pb, Se, or Zn in supercritical (SC) fluid extractor
      eluate. In operation, analyte metal in aqueous medium is derivatized by in situ
      complexation with tetrabutylammonium dibutyldithiocarbamate (TBADB-DTC) and the
      product complex is mobilized into SC-CO2. The extraction process is equally
      efficient whether the mobile phase is presaturated with complexing agent during a
      static preequilibration stage of the process or this reagent is solubilized
      dynamically as the mobile phase traverses a saturation vessel placed in series
      with the extraction vessel. SC-CO2 extractor eluate is nebulized into a diffused
      flame maintained within the upper region of the flame tube and the optical tube
      of the interface. Optimal flame conditions maintained with separate flows of O2
      and H2 to the base of the flame tube are slightly reducing for aqueous and SC-CO2
      mobile phases but slightly oxidizing for a methanolic mobile phase. For each
      analyte element, limits of detection were subnanogram to low picogram if standard
      was flow injected into the mobile phase. These sensitivities permitted
      differences in the rates of mobilization of analyte metal from different matrices
      to be explored as a technique for probing the interactions of the analyte metal
      with the matrix. A portion of the total Zn burden of fresh bovine liver slurry
      was rapidly mobilized in the absence of complexing agent, and the remainder was
      solubilized more rapidly than the Zn in a freeze-dried standard reference
      material of this tissue.

PMID- 7810899
TI  - Conformational changes in the reversed phase liquid chromatography of recombinant
      human growth hormone as a function of organic solvent: the molten globule state.
AB  - As a continuation of a previous paper on the retention behavior of recombinant
      human growth hormone (rhGH) in reversed phase chromatography at pH 6.5 (Oroszlan,
      P., et al. Anal. Chem. 1992, 64, 1623-1631) the effect of 1-propanol (1-PrOH) and
      acetonitrile on the conformation of rhGH at this pH has been investigated by
      circular dichroism (CD), second-derivative UV spectroscopy, fluorescence
      anisotropy, fluorescence quenching, and fluorescence lifetime measurements.
      Addition of 1-PrOH up to a concentration of 10% (v/v) does not cause any
      significant changes in protein structure. However, above this concentration, a
      transition from the native to a new state is observed; the transition is
      completed above 30% (v/v) of 1-PrOH, the composition for completion being
      dependent on temperature. This change in structure correlates with retention
      changes observed in reversed phase chromatography. The new rhGH conformation
      retains much of the alpha-helicity and possesses a slightly expanded hydrodynamic
      radius relative to native rhGH. Second-derivative UV spectroscopy suggests that
      the hydrogen bond between Trp 86 and Asp 169, spanning two alpha-helices, remains
      intact. On the other hand, the near-UV CD intensity changes from positive to
      negative in the Trp region of the spectrum, signaling an alteration in the Trp
      environment. In addition, fluorescence quenching measurements with
      trichloroethanol reveal greater accessibility to solvent of the Trp residue after
      the conformational transition has occurred. From the results, it is concluded
      that a molten globule state (compact state retaining much of the secondary
      structure of the native state but with a disrupted tertiary structure) is
      produced with the addition of > 30% (v/v) 1-PrOH.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7810900
TI  - Liquid chromatography/mass spectrometry of phospholipids using electrospray
      ionization.
AB  - An improved technique for phospholipid molecular species analysis was developed
      using high-performance liquid chromatography/mass spectrometry with the
      electrospray interface. Using the 0.5% ammonium hydroxide in a water-methanol
      hexane mixture and a C-18 column, complex mixtures of phospholipid molecular
      species were separated and detected mainly as protonated or natriated molecular
      species. The response was linear over 2 orders of magnitude, allowing
      quantification of each molecular species. In comparison to the existing LC/MS
      techniques, marked improvement in sensitivity was observed. The present
      quantification limit is approximately 0.5 pmol before split (5 fmol after 1/100
      split). The relative responses were more dependent on the head group identity
      rather than fatty acyl composition within a phospholipid class. In general,
      phosphatidylcholine (PC) species are most sensitively detected followed by
      phosphatidylethanolamine (PE) species. The sensitivity of phosphatidylserine (PS)
      in the positive ion mode is approximately 20 times less in comparison to PC under
      our condition.

PMID- 7810901
TI  - Chiral resolution of cationic drugs of forensic interest by capillary
      electrophoresis with mixtures of neutral and anionic cyclodextrins.
AB  - Chiral resolution of a number of cationic drugs of forensic interest
      (amphetamine, methamphetamine, cathinone, methcathinone, cathine, cocaine,
      propoxyphene, and various alpha-hydroxyphenethylamines) is achieved via capillary
      electrophoresis (CE) with added cyclodextrins (CDs), including novel mixtures of
      neutral and anionic CDs. In the latter studies, resolution and migration speed
      are readily adjusted by varying the ratio of the two added CDs, as the anionic CD
      acts as a counter-migrating complexing reagent. The neutral CD, heptakis(2,6-di-O
      methyl)-beta-CD, was found suitable for the analysis of illicit cocaine and khat
      leaves (Catha edulis Forsk), which contain (-)-alpha-aminopropiophenone ((-)
      cathinone), (+)-norpseudoephedrine (cathine), (-)-norephedrine, and trace levels
      of the phenylpentenylamines (+)-merucathinone, (+)-merucathine, and possibly (-)
      pseudomerucathine. The use of mixtures of the neutral and the anionic CD (beta-CD
      sulfobutyl ether IV) was found suitable for the analysis of illicit amphetamine,
      methamphetamine, methcathinone, and propoxyphene. A model is presented for the
      impact of mixtures of neutral and anionic CDs on migration behavior and chiral
      resolution in CE.

PMID- 7810902
TI  - Fluorescein isothiocyanate-labeled protein G as an affinity ligand in
      affinity/immunocapillary electrophoresis with fluorescence detection.
AB  - Antibodies from human sera (h-IgG) were tagged with a fluorescent dye
      (fluorescein isothiocyanate, FITC) through the affinity reaction of FITC-labeled
      protein G with the Fc fragment of the antibodies. The complexes were quantified
      by capillary zone electrophoresis (CZE) within 1 min, i.e., fast enough to
      prevent their dissociation during the measurement. Conditions for the affinity
      reaction and the CZE analysis could thus be optimized independently. When an FITC
      labeled protein G concentration of 10(-6) mol/L was used, h-IgG concentrations
      between 10(-6) and 10(-9) mol/L were reproducibly quantified (STD < 2%), using an
      LIF detector. A correlation coefficient, r2, of 0.9988 was established between
      the peak height and the IgG concentration. Alternatively, h-IgG containing serum
      samples and the FITC-labeled protein G were simply injected into the CE capillary
      in consecutive zones, followed by the application of the electrical field. Within
      2 min, the affinity complexes were resolved and the IgG content of the serum
      quantified (r2 = 0.9986). The injection sequence was of no consequence. The
      measurements agreed well with those found in a single radial immunodiffusion
      (SRID) assay. In addition FITC-labeled protein G-tagged anti-h-IgG1 antibodies
      were used to detect the specific antigen of the involved antibody, namely, h
      IgG1, in human sera.

PMID- 7810903
TI  - Separation of fragments up to 570 bases in length by use of 6% T non-cross-linked
      polyacrylamide for DNA sequencing in capillary electrophoresis.
AB  - Non-cross-linked polyacrylamide is a very convenient medium for the separation of
      DNA sequencing fragments in capillary electrophoresis. We demonstrate DNA
      sequencing with this matrix at an electric field of 200 V/cm and at room
      temperature. Resolution is observed to decrease exponentially with fragment
      length. Fragments 570 bases in length generate a resolution of 0.5, which is
      adequate for sequence identification.

PMID- 7810904
TI  - Determination of planar PCBs by combining on-line SFE-HPLC and GC-ECD or GC/MS.
AB  - A method for determining non-ortho- and mono-ortho-substituted polychlorinated
      biphenyls (PCBs) in biological samples has been developed. High selectivity was
      obtained by on-line coupling of supercritical fluid extraction (SFE) and high
      performance liquid chromatography (HPLC). Gas chromatography (GC) with electron
      capture detection or high-resolution mass spectrometry was utilized for
      quantitative determinations. Group separation of different PCB congeners was
      achieved on a (2-(1-pyrenyl)ethyl)dimethylsilylated silica column. Compared with
      off-line HPLC, the on-line coupling to SFE resulted only in a minor reduction in
      column efficiency. The average recoveries of the planar non-ortho-substituted PCB
      congeners 77, 126, and 169 from crab hepatopancreas were 71-101%, with the
      highest recovery for PCB-169. For human blood serum and milk, the recoveries of
      the three congeners ranged from 35 to 57% (serum) and from 76 to 87% (milk), with
      the lowest recovery for PCB-169. The relative standard deviations of the complete
      analyses were determined to be 5-16%. The recoveries of the on-line SFE-HPLC
      technique were compared to those of conventional solvent extraction and off-line
      HPLC. For crab hepatopancreas, the two methods gave approximately the same
      result, but for blood serum, slightly higher recovery of the native non-ortho
      substituted PCBs was obtained using SFE-HPLC. The present method demonstrates the
      high speed and selectivity which were obtained by on-line SFE-HPLC as a sample
      preparation technique prior to GC analyses for the determination of a group of
      highly toxic PCBs, usually found in very low concentrations compared to the bulk
      of the PCB congeners.

PMID- 7810905
TI  - Use of cyclodextrins for prepurification of progesterone and testosterone from
      human serum prior to determination with isotope dilution gas chromatography/mass
      spectrometry.
AB  - A new application of cyclodextrins is presented, being their use for sample
      purification. This new application is exemplified with a method for the
      determination of progesterone and testosterone in human serum based on isotope
      dilution gas chromatography/mass spectrometry. The whole procedure consists of a
      traditional solvent extraction with hexane for progesterone, respectively
      dichloromethane for testosterone, followed by a back-extraction of the steroids
      into a cyclodextrin-water solution. After washing of the aqueous phase with
      hexane, the steroids are finally extracted with toluene (progesterone) and
      dichloromethane (testosterone). Different cyclodextrins and cyclodextrin
      derivatives in various concentrations are investigated. A solution of 150 mmol/L
      hydroxypropyl beta-cyclodextrin in water is selected. The recovery of
      progesterone and testosterone is 70 and 80% respectively. The purification
      effectiveness, accuracy, and precision of the new method are equivalent to a
      traditional method using gel chromatography for sample purification.

PMID- 7810906
TI  - Perspectives: a vital biomechanical model of synovial joint design.
AB  - Making a durable joint requires adapting the one present at birth to its
      subsequent mechanical usage and then maintaining it. The total loads on a joint's
      momentarily loaded area plus the size of that area determine the unit loads on
      its articular cartilage and subchondral bone. Given those facts, this model
      suggests the following. For adaptation: As is true for bone, a threshold range of
      unit loads that could turn cartilage modeling ON would lie below this tissue's
      microdamage threshold. When a joint's unit loads rose to that modeling threshold,
      chondral modeling would begin enlarging the momentarily loaded area to reduce and
      keep the unit loads on it below the microdamage thresholds of the bone and
      cartilage supporting that area. For maintenance: Maintenance activities would
      control the stiffness of cartilage and bone, which would also affect a joint's
      momentarily loaded area. These activities would usually repair whatever
      microdamage normally arises in those tissues, and could modify their microdamage
      thresholds too. In children, modeling and maintenance in bone and cartilage would
      function effectively. In adults chondral modeling becomes ineffective, but
      maintenance activities in bone and cartilage would remain effective, and likewise
      for modeling in the subchondral bone. This model assigns special importance in
      joint design to the stiffness of bone, cartilage, and ligament (as distinguished
      from their strength), to the typical largest unit loads applied to them by a
      subject's usual weekly physical activities, and to their microdamage.

PMID- 7810907
TI  - Endothelial injury following experimental subarachnoid hemorrhage in rats:
      effects on brain blood flow.
AB  - BACKGROUND: The leading cause of death and disability in patients suffering from
      aneurysmal subarachnoid hemorrhage (SAH) is cerebral vasospasm, a persistent,
      progressive, and often irreversible constriction of cerebral arteries. A wide
      array of pathological changes occur in cerebral arteries following SAH, with
      endothelial injury being the earliest and most consistent one. Since intact
      endothelium modulates many reflexes that influence vascular tone, damage to them
      may represent a significant contributor to cerebral vasospasm. METHODS: Changes
      in local cerebellar blood flow (LCBF) and pathological alterations in major
      cerebral arteries were studied and compared in rats at various time intervals
      following SAH. SAH induced by the subarachnoid injection of 0.3 ml of whole
      blood. Sham rats received a subarachnoid injection of 0.3 ml of isotonic saline.
      RESULTS: Except for an immediate but transient decrease, LCBF remained unchanged
      over a 3 day period following saline injection. Likewise, there were no
      pathological alterations in cerebral arteries of saline-injected rats. In
      contrast, the subarachnoid injection of whole blood produced significant changes
      in both LCBF and cerebral arteries. Within 30 minutes post-blood injection, LCBF
      became significantly decreased and remained so for 4 hours. However, within 24
      hours, LCBF had returned to control levels where it remained for 3 days.
      Endothelial injury was observed in the basilar and middle cerebral arteries from
      30 minutes through 4 hours, the same periods in which LCBF was significantly
      reduced. Within 24 hours, the time period in which LCBF had rebounded to control
      ranges, cerebral arteries showed no evidence of endothelial damage and resembled
      control cells. CONCLUSION: The results indicate a direct correlation between
      changes in LCBF and the structural integrity of endothelial cells in the early
      stages following SAH. The lack of chronically depressed LCBF (after 1 day) may be
      related to the quick structural repair of endothelium.

PMID- 7810908
TI  - Morphometry of the kidney in rat pups from uninephrectomized mothers.
AB  - BACKGROUND: The present study was designed to explore whether maternal renal
      dysfunction affects fetal kidney development and if the effects are lasting
      during the postnatal development. METHODS: Kidneys of 1-day-old and 6-week-old
      pups from mothers which were uninephrectomized on day 5 of gestation were
      studied. RESULTS: One day after birth, both the number of immature glomeruli and
      average volume of mature glomeruli of the neonates from uninephrectomized mothers
      were significantly larger than those from sham-operated mothers. Six weeks after
      birth, no significant differences in parameters of the kidney were observed
      between the pups from uninephrectomized and those from sham-operated mothers.
      Furthermore, blood urea nitrogen (BUN) concentration in adult female rats was
      determined at various days after uninephrectomy. BUN concentration in
      uninephrectomized rats was significantly higher than that in sham-operated ones.
      CONCLUSIONS: These results suggest that the fetal kidney development is
      accelerated by the elevated BUN level following maternal uninephrectomy and that
      the renotropic activity does not last during the postnatal developmental period.

PMID- 7810909
TI  - Expression of epidermal growth factor receptor (EGFr) immunoreactivity in human
      cutaneous nerves and sensory corpuscles.
AB  - BACKGROUND: The epidermal growth factor receptor (EGFr) binds both epidermal
      growth factor (EGF) and transforming growth factor alpha (TGF alpha), which are
      currently considered among putative growth factors playing a role in the nervous
      system. EGFr and their ligands have been localized in the mammalian peripheral
      nervous system. The present study was undertaken to investigate whether nerves
      and sensory corpuscles supplying human glabrous skin express EGFr. METHODS:
      Formaldehyde fixed, paraffin embedded samples of finger-tip digital skin obtained
      from adult healthy subjects were processed for indirect PAP immunohistochemistry
      using a monoclonal antibody against an epitope of the intracellular domain of
      EGFr. To ascertain the localization of EGFr immunoreactivity, neurofilament
      proteins (NFP), S100 protein (S100P), and epithelial membrane antigen (EMA) were
      studied in parallel to label axons, Schwann cells, and perineurial cells,
      respectively, as well as their corpuscular derivatives. RESULTS: A variable
      intensity of EGFr immunostaining was regularly observed in the perineurium and
      Schwann cells, and occasionally in the axons of nerve bundles. EGFr
      immunoreactivity was also present in the axon and lamellar cells of Meissner
      corpuscles, and within the axon, inner-core, outer-core, and capsule of Pacinian
      corpuscles. CONCLUSIONS: Present results demonstrate that human cutaneous nerves
      and sensory corpuscles express EGFr suggesting a role for peptides able to bind
      EGFr, i.e., EGF and TGF alpha, in the human peripheral nervous sensory system.

PMID- 7810910
TI  - Enrichment of glutamate immunoreactivity in lemniscal terminals in the
      ventropostero lateral thalamic nucleus of the rat: an immunogold and WGA-HRP
      study.
AB  - BACKGROUND: The ventropostero lateral nucleus (VPL) is a thalamic somatosensory
      center receiving inputs from limbs and trunk; some of this input is via terminals
      of the dorsal column medial lemniscal pathway. These fibers convey non-noxious
      somesthesic information. METHODS: In this study the neurochemical content of
      lemniscal afferents in VPL of rats was investigated at the electron microscopic
      level by combining anterograde transport of horseradish peroxidase conjugated to
      wheat germ agglutinin, injected in the dorsal dorsal column nuclei, with
      postembedding immunogold labeling for glutamate (Glu). RESULTS: Anterograde
      labeling in VPL was detected only in myelinated axons and in large terminals
      containing round synaptic vesicles, interpreted as lemniscal afferents.
      Quantitative evaluation of gold particle density showed enrichment of Glu
      immunolabeling in the identified lemniscal terminals with respect to other
      neuronal profiles. Observation of serial sections immunoreacted for Glu
      demonstrated consistency of labeling, whereas in alternate sections immunoreacted
      for Glu and for the inhibitory amino acid GABA these two antigens were always
      present in distinct types of terminals. CONCLUSIONS: These findings are in
      agreement with several lines of evidence, obtained with different experimental
      approaches, supporting the hypothesis that Glu plays a major role in conveying
      sensory stimuli to the thalamus from second order neurons in the dorsal column
      nuclei.

PMID- 7810911
TI  - Fine structure of the anteromedial eye of the liphistiid spider, Heptathela
      kimurai.
AB  - BACKGROUND: The presence of efferent fibers in the anteromedial eye of liphistiid
      spiders kept in natural daily cycles of illuminance has been reported. However,
      this report is limited to innervation by the efferent fiber and daily rhabdomal
      changes, and there have been no detailed ultrastructural accounts of the eye.
      METHODS: The fine structure of this eye was examined by electron microscopy.
      RESULTS AND CONCLUSIONS: The eye consists of a cornea, a lens, a vitreous body,
      and a retina. The retina contains 13 or 14 receptor cells and glial cells. The
      rhabdoms are distal to the nuclei of the receptor cells. In the distal region of
      the receptive segment, the rhabdomeres lie in the center of the cell. In the
      middle region, anisomorphic rhabdoms formed by microvilli from adjacent cells are
      at the cell periphery. In the proximal region, the rhabdomeres are situated in
      the center of the cell. The ocellar nerve of the eye runs toward the
      protocerebrum and enters the posterior part of the first optic ganglion of the
      secondary eyes. Pigmented cells and nonpigmented cells are observed. The
      pigmented cells are located in the most lateral of the eye and cover the whole
      eye. The nonpigmented cells are located in the receptor cell bodies and extend to
      the origin of the ocellar nerve. They wind to form capillaries filled with
      electron-dense material. These structures are discussed in comparison with those
      of other spiders and other chelicerates.

PMID- 7810912
TI  - Perspectives: a biomechanical model of the pathogenesis of arthroses.
AB  - This model views the common, initiating cause of arthroses as excessive articular
      cartilage microdamage. If so, understanding it would become a central problem for
      understanding the pathogenesis of arthroses. The model proposes the microdamage
      can stem from: (1) Excessive total loads on normal joints; (2) underadaptations
      in a joint's size or shape that leave its momentarily loaded area too small for
      normal loads; (3) impaired microdamage repair in subchondral bone or articular
      cartilage; (4) abnormal composition or structure that makes a tissue develop
      excessive microdamage under normal loads. (5) (2)-(4) above could stem from
      changed set points or "lead times" for a joint's adaptations and maintenance,
      which in turn could stem from (6) genetic influences, some drugs, toxins,
      diseases, and "X," and (7) from combinations of the above. In the pathogenesis of
      arthroses this model assigns special importance to the stiffness of joint tissues
      (as distinguished from their strength), to the typical largest unit loads they
      carry as a result of a subject's usual physical activities, and to microdamage in
      those tissues.

PMID- 7810913
TI  - Ultrastructural modifications of vesicular and Golgi elements in the
      Saccharomyces cerevisiae sec21 mutant at permissive and non-permissive
      temperatures.
AB  - BACKGROUND: The secretory protein transit between cisternae of endoplasmic
      reticulum (ER) and Golgi elements is blocked when the yeast Saccharomyces
      cerevisiae sec21 mutant is shifted from the permissive (24 degrees C) to a non
      permissive (37 degrees C) temperature, but 30-50 nm vesicles accumulate in the
      cytoplasm. At the semi-permissive temperature of 33 degrees C there is no
      complete block but rather a slowdown of the protein transport between ER and
      Golgi. The purpose of the present investigation is to analyze the structural
      expression of these events. METHODS: S. cerevisiae sec21 mutants were maintained
      for 90 min at semi-restrictive (33 degrees C) or restrictive (37 degrees C)
      temperatures and then progressively returned to 24 degrees C. Following fixation
      in glutaraldehyde and a postfixation in potassium ferrocyanide reduced osmium,
      0.08 to 0.2 microns thick sections were cut from Epon embedded yeasts. Using the
      thicker sections, stereopairs of electron microscope photographs were prepared
      and used to visualize the three-dimensional configuration of the organelles.
      RESULTS: At permissive temperature, the Golgi elements appeared as isolated
      networks of membranous tubules dispersed throughout the cytoplasm. The diameter
      of these membranous tubules varied considerably from one Golgi element to
      another. Larger tubules showed at their intersections distensions with size and
      staining intensity comparable with that of the secretory granules seen at
      proximity of the Golgi networks or at the cell periphery. Small vesicles in the
      30-50 nm size range were rarely if ever observed in cells grown at permissive
      temperature. Golgi networks and secretion granules were less conspicuous in
      mutant cells maintained at 33 degrees C and completely disappeared at 37 degrees
      C. In both cases, the main structural feature was the presence in the cytoplasm
      of numerous small vesicles and of short membranous tubules with a diameter
      identical to that of the small vesicles. As soon as 5 minutes after shifting
      mutants from 33 degrees C to 24 degrees C, the small vesicles disappeared from
      the cytoplasm, while secretory granules were actively produced in extensively
      developed Golgi network. When mutants were returned from 37 degrees C to 24
      degrees C, the disappearance of small vesicles was more progressive and
      concomitant with the progressive reconstruction of Golgi networks. CONCLUSIONS:
      It is thus postulated that, in the above mentioned conditions, the small vesicles
      of the sec21 mutant did not act as intermediate carriers between the endoplasmic
      reticulum and a pre-existing Golgi apparatus, but rather fused together to
      produce newly formed Golgi networks.

PMID- 7810915
TI  - Androgenic control of porphyrin in the Harderian glands of the male Syrian
      hamster is modulated by the photoperiod, which suggests that the sexual
      differences in porphyrin concentrations in this gland are important functionally.
AB  - BACKGROUND: The porphyrin concentrations of the Harderian glands of Syrian
      hamsters show marked sexual differences, with male levels being much lower than
      those of females. Porphyrinogenesis is inhibited by androgens, so orchidectomy
      leads to elevated male porphyrin concentrations; however, a number of other
      procedures (some of which also lower androgen levels) prevents this. We studied
      the effects of short-day photoperiods and melatonin on Harderian porphyrin
      concentrations. METHODS: Intact, castrated, or pinealectomized hamsters of both
      sexes were exposed to long-day or short-day photoperiods. Intact or castrated
      hamsters were given melatonin injections in the morning or the afternoon, or were
      given beeswax pellets containing melatonin. After a variable period, Harderian
      glands were dissected and porphyrins were measured. RESULTS: Prolonged short-day
      exposure (13 weeks) led to increased Harderian porphyrin concentrations and this
      rise was prevented by pinealectomy. The rise in Harderian porphyrins following
      short-day exposure was small, compared with that following castration. Short-day
      photoperiods also prevented the rise in porphyrin levels associated with
      castration and this effect was prevented by removal of the pineal. Melatonin
      injections, whether given in the morning or in the afternoon, had no effect on
      Harderian porphyrin concentration of castrated male hamsters. Continuous release
      melatonin pellets reduced the postcastrational rise in porphyrin levels in one
      experiment, while having no effect in another. In female hamsters, neither short
      photoperiods nor melatonin pellets influenced Harderian porphyrin concentrations.
      CONCLUSIONS: These results suggested that a factor from the pineal gland helps
      maintain the low levels of porphyrin which are characteristic of male Harderian
      glands, despite the decrease in androgen levels which typically results from
      exposure to short days. Morning and afternoon injections of melatonin and
      continuous release melatonin pellets failed to resolve the question of whether
      this pineal factor is melatonin. Our results demonstrated that low male and high
      female porphyrin levels are maintained in Syrian hamsters, despite seasonal
      variations in the hormonal milieu, suggesting that these sexual differences are
      important for the (still unestablished) function of the Harderian glands in this
      species.

PMID- 7810914
TI  - Electron microscopic and histochemical studies of the mononuclear odontoclast of
      the human.
AB  - BACKGROUND: Osteoclasts and odontoclasts are multinucleated giant cells which
      resorb hard tissue by the ruffled borders. Recently, the authors reported the
      presence of a mononuclear osteoclast with a ruffled border in vitro. However, its
      presence in vivo has not been shown. To demonstrate the presence of a mononuclear
      odontoclast in humans, the present study used human deciduous teeth. METHODS:
      After fixation and decalcification, tartrate-resistant acid phosphatase
      (TRACPase) activity was detected with the azo dye method, and then TRACPase
      positive cells were observed on resorbing areas of teeth. TRACPase-positive cells
      could be distinguished from other cells by light microscopy, and the cells for
      investigation were serially sectioned by alternating semithin and ultrathin
      sections to observe their ultrastructure and three-dimensional organization.
      RESULTS: TRACPase activity was detected in both multinucleated odontoclasts and a
      mononuclear cell from serial sections. By electron microscopy, most of the
      multinucleated odontoclasts had ruffled borders and clear zones. A mononuclear
      TRACPase-positive cell with a ruffled border and clear zone was reconstructed
      three-dimensionally by NIKON COSMO-ZONE 2SA. The reconstruction showed that this
      cell had one irregularly shaped nucleus and a wide ring-shaped clear zone and a
      small ruffled border. Under the ruffled border, this cell formed a small lacuna
      on the dentin surface. The results suggested that this cell was a mononuclear
      odontoclast. CONCLUSIONS: The present study concludes that cells with ruffled
      borders and clear zones observed by transmission electron microscopy can be
      identified as odontoclasts or osteoclasts irrespective of the number of nuclei.

PMID- 7810916
TI  - Embryonic-maternal cell interactions at implantation in the fat-tailed dunnart, a
      dasyurid marsupial.
AB  - BACKGROUND: In marsupials implantation occurs about two-thirds the way through
      the short gestation before which time the embryo is surrounded by the permeable
      shell membrane which prevents physical contact between the trophoblast and
      uterine epithelium. Although the trophoblast has been shown to be invasive to
      varying degrees in several species of marsupials, the ultrastructure of the
      embryonic-uterine cell interactions at the time of implantation has not been
      described in this group. METHODS: Thick plastic sections and transmission
      electron microscopy were employed to investigate the cellular interactions at
      implantation in the fat-tailed dunnart (Sminthopsis crassicaudata), a dasyurid
      Australian marsupial. RESULTS: Our results show that epithelial penetration
      begins when the embryo is at the late presomite/early somite stage. In the
      trilaminar region of the yolk sac (TYS), trophoblast cells adjacent to the embryo
      form desmosomes with uterine epithelial cells and also appear to fuse with them
      to form hybrid cells, the cytoplasm of which resembles that of trophoblast. Later
      in the TYS, as the placenta develops, trophoblast microvilli and larger cell
      processes invaginate, and interdigitate with, the highly folded maternal
      epithelium but do not invade it. At this time in the bilaminar, or avascular,
      yolk sac (BYS), multinucleate trophoblast giant cells (TGCs) from an annular
      region adjacent to the sinus terminalis intrude between, and possibly fuse with,
      the maternal epithelium. The invading TGCs spread laterally above the residual
      basal lamina before migrating into the stroma. CONCLUSIONS: In this species of
      marsupial at least, the cell interactions at the time of implantation are similar
      to those seen in some eutherian species despite the fact that the fetal chorion
      is of yolk sac rather than allantoic origin.

PMID- 7810917
TI  - Regional variations in the ultrastructural features of secretory cells in the rat
      oviductal epithelium.
AB  - BACKGROUND: In mammals, the oviductal secretory cells and their secretions play
      important roles in reproductive and developmental events. Therefore, many
      electron microscopic studies of mammalian oviductal epithelial cells have been
      performed. METHODS: The secretory cells in various regions of the rat oviduct
      during the estrous cycle were examined by transmission electron microscopy.
      RESULTS: In the fimbriae, the secretory cells contained small secretory granules
      with moderately electron-dense matrices and many large bodies that resembled
      lipid droplets. In the ampullar cells, small secretory granules with moderately
      electron-dense matrices were observed in the apical cytoplasm. In the isthmus,
      the secretory cells contained numerous secretory granules with moderately
      electron-dense matrices. Electron-dense areas were frequently observed in many of
      the granules of the isthmic cells. Vesicles, partially filled with a dense
      substance, frequently were observed in the isthmic cells and occasionally in the
      ampullar cells. Very long stereocilia projected from the surfaces of the isthmic
      secretory cells into the lumen. Exocytosis of the secretory granules was
      observed. In addition, there was evidence to suggest the release of the bodies
      that resembled lipid droplet occurred. Cysts and ciliated vacuoles that appeared
      to be intraepithelial were frequently observed in the fimbrial and ampullar
      epithelia. No dramatic changes in the relative numbers of ciliated and secretory
      cells in any oviductal segment were observed during the estrous cycle.
      CONCLUSIONS: Our ultrastructural observations of the rat oviduct revealed marked
      regional variations in the morphological features of secretory cells. These
      results may provide insight into regional and cellular differences in the
      function of the rat oviduct.

PMID- 7810918
TI  - Developmental expression of immobilin in the rat epididymis.
AB  - BACKGROUND: Immobilin is a protein secreted by principal cells of the distal
      initial segment, intermediate zone and caput epididymidis of adult rats, which
      serves to immobilize spermatozoa. In the distal cauda, epithelial clear cells are
      involved in its endocytosis. The objective of this study was to correlate the
      developmental events in the maturation of the epididymis with the timing of
      immobilin secretion and endocytosis in order to evaluate the testicular or
      epididymal factors which may influence or regulate immobilin expression. METHODS:
      Our approach was to follow and compare the developmental expression of immobilin
      by light microscope immunocytochemistry in control and efferent duct ligated rats
      of different postnatal ages. RESULTS: Coincident with the morphological
      maturation of the principal cells by postnatal day 39, immobilin displayed the
      characteristic secretory immunostaining pattern found in adults. This adult-like
      expression occurred despite the absence of spermatozoa in the lumen but was
      coincident with high levels of circulating and luminal androgens. In contrast,
      immobilin secretion in rats whose efferent ducts were ligated at day 15 was weak
      to non-existent in the principal cells of the caput epididymidis at day 28 and
      remained so into adulthood, indicating that principal cells of this region of the
      epididymis are dependent either directly or indirectly upon testicular factors
      present in the lumen for immobilin expression. However, secretion of immobilin in
      the principal cells of the distal initial segment was unaffected by ligation and
      unlike the case in control rats high levels of immobilin also continued to be
      secreted into adulthood by the principal cells of the proximal initial segment.
      Thus in the distal initial segment immobilin secretion is not regulated by
      luminal factors originating from the testis, while in the proximal initial
      segment the normal suppression of immobilin that occurs by postnatal day 39 is.
      Despite ligation, endocytosis of immobilin by clear cells of the distal cauda
      epididymidis occurred by day 49, indicating that luminal testicular factors are
      not essential for stimulating the uptake of immobilin by these cells.
      CONCLUSIONS: The results taken together suggest that there are stimulatory and
      inhibitory luminal testicular factors involved in the regional development of
      immobilin secretion in the epididymis. There are also immobilin secreting regions
      in the epididymis, whose secretory development is independent of luminal
      testicular factors.

PMID- 7810919
TI  - ANA presents oral argument before the NLRB on supervisory status of nurses.

PMID- 7810920
TI  - Children: a community in crisis.

PMID- 7810921
TI  - ANA and SNAs testify on risks of decreasing skill mix.

PMID- 7810922
TI  - The PAC reality: Indiana's experience.

PMID- 7810924
TI  - Nurses gain ground during reform debate.

PMID- 7810923
TI  - EMFP cost-sharing program benefits minority fellows.

PMID- 7810925
TI  - School-based nursing fills gaps in adolescent health care.

PMID- 7810926
TI  - Ethics survey looks at nurses' experiences.

PMID- 7810927
TI  - Continuing education program: integrating an understanding of sleep knowledge
      into your practice. Part 2. Screening for sleep-related disorders: sleep apnea
      and narcolepsy (continuing education credit).

PMID- 7810929
TI  - REform shifts to the states.

PMID- 7810928
TI  - Profession mourns loss of Barbara Fassbinder.

PMID- 7810930
TI  - Now what for health care, ANA and America's nurses?

PMID- 7810931
TI  - RN health affected by 'sick buildings'.

PMID- 7810933
TI  - Extrahepatic immunologic manifestations in chronic hepatitis C and hepatitis C
      virus serotypes.
AB  - OBJECTIVE: To determine, using a serotyping assay, whether the occurrence of
      extrahepatic immunologic disorders in patients with chronic hepatitis C is
      dependent on hepatitis C virus serotype. DESIGN: Prospective study. SETTING:
      Liver unit and virology laboratory of a university hospital. PATIENTS: 59
      consecutive patients with chronic hepatitis C. MEASUREMENTS: Hepatitis C virus
      serotype was determined using a recently developed immunoenzymatic assay that
      detects antibodies directed to serotype-specific immunodominant epitopes.
      Cryoglobulin, rheumatoid factor, and numerous antitissue antibodies were sought.
      Biopsies of labial salivary glands were done in 49 of the 59 patients. RESULTS:
      Prevalence was 59% for serotype 1, 10% for serotype 2, 12% for serotype 3, and 3%
      for mixed infection. Fifteen percent of patients could not be serotyped.
      Cryoglobulinemia was found in 36% of patients and rheumatoid factor was found in
      the serum of 71%. At least one antitissue antibody was found in the serum of 41%
      of patients; salivary gland biopsy showed lymphocytic capillaritis in 49% of
      patients. These immunologic abnormalities were seen in patients infected with any
      of the three serotypes, and prevalences of the abnormalities did not differ
      significantly among patients infected with different serotypes. CONCLUSIONS: We
      confirm that the prevalence of extrahepatic immunologic abnormalities is high in
      patients with chronic hepatitis C. These abnormalities may occur in patients
      infected with any of the three major hepatitis C virus serotypes now present in
      developed countries.

PMID- 7810932
TI  - Hepatitis C virus type 1b (II) infection in France and Italy. Collaborative Study
      Group.
AB  - OBJECTIVE: To analyze the distribution of hepatitis C virus (HCV) genotypes among
      patients positive for antibody to HCV (anti-HCV) according to age, severity of
      liver disease, and duration of infection; to investigate the influence of HCV
      genotypes on response to interferon-alpha therapy; and to study HCV viremia
      levels in relation to genotypes and severity of liver disease. DESIGN: Cross
      sectional study. SETTING: 3 university hospitals and 2 research units. PATIENTS:
      3 groups of French and Italian patients with chronic HCV infection and detectable
      serum HCV RNA: Group 1 included 35 patients with hepatocellular carcinoma; group
      2, 71 patients with cirrhosis who did not have hepatocellular carcinoma; and
      group 3, 114 patients with chronic active hepatitis. 106 of the patients with
      chronic hepatitis or cirrhosis were treated with interferon-alpha (3 MU
      subcutaneously 3 times/wk for > or = 6 months). MEASUREMENTS: Genotyping by
      polymerase chain reaction with capsid-specific primers; serum HCV RNA by branched
      DNA (bDNA) signal amplification. RESULTS: Hepatitis C virus genotype 1b (II) was
      the most prevalent genotype (61.8%). In a univariate analysis, it was associated
      with older age (< 40 years, 47.4%; > or = 60 years, 80.4%; P = 0.001), longer
      duration of disease (< or = 10 years, 40.4%; > or = 20 years, 86.7%; P = 0.005),
      and cirrhosis with or without hepatocellular carcinoma (78.4% compared with 53.8%
      for chronic hepatitis; P < 0.001). Viremia levels did not differ between patients
      infected with HCV type 1b (II) and those infected with other HCV genotypes.
      Patients with HCV type 1b (II) responded to interferon-alpha therapy
      significantly less than did patients with other HCV genotypes (P = 0.01). In a
      multivariate analysis, age and cirrhosis were independently associated with HCV
      genotype 1b (II). Genotype and HCV viremia level were independent predictors of
      response to interferon-alpha therapy. CONCLUSIONS: The prevalence of HCV
      genotypes in French and Italian patients has been changing; the prevalence of HCV
      type 1b (II) infection has progressively decreased, although it still accounts
      for most HCV-related cirrhosis and hepatocellular carcinoma. High HCV viremia
      levels and HCV genotype type 1b (II) are independent predictors for poor response
      to interferon-alpha therapy and should be considered in the management of
      patients with HCV infection.

PMID- 7810934
TI  - Family studies in patients with the sleep apnea-hypopnea syndrome.
AB  - OBJECTIVE: To determine whether familial factors affect development of the sleep
      apnea-hypopnea syndrome and upper airway caliber. DESIGN: A case-control study.
      SETTING: Tertiary, referral clinical sleep laboratory. PARTICIPANTS: 51 first
      degree relatives of patients with the sleep apnea-hypopnea syndrome and 51
      controls matched for age, sex, height, and weight who were drawn at random from a
      family practice register. To avoid studying the familial nature of obesity, only
      relatives of index patients with body mass indices less than 30.0 kg/m2 were
      recruited. MEASUREMENTS: Assessment of sleep-related symptoms; breathing, sleep,
      and oxygenation patterns on overnight polysomnograms; upper airway dimensions by
      acoustic reflection; and facial structure by lateral cephalometry. RESULTS: More
      relatives of patients with the sleep apnea-hypopnea syndrome reported snoring (24
      relatives compared with 7 controls; P < 0.001) and daytime sleepiness (28
      relatives compared with 16 controls; P = 0.01). Relatives had more apneas and
      hypopneas per hour (median of 13/h [95% CI, 3 to 82/h] for relatives compared
      with median of 4/h [CI, 0 to 53/h] for controls; P < 0.001), more arousals from
      sleep (30/h [CI, 11 to 87/h] for relatives compared with 17/h [CI, 4 to 59/h] for
      controls; P < 0.001), poorer sleep quality, and more oxygen desaturations.
      Relatives also had narrower upper airways with retroposed maxillae and mandibles
      and longer soft palates with wider uvulae. CONCLUSION: The sleep apnea-hypopnea
      syndrome has a strong familial component. The familial tendency may be caused by
      differences in facial structure.

PMID- 7810935
TI  - Continuous aspiration of subglottic secretions in preventing ventilator
      associated pneumonia.
AB  - OBJECTIVE: To determine whether continuous subglottic aspiration prevents
      nosocomial pneumonia in mechanically ventilated patients. DESIGN: A randomized,
      controlled, blinded study. SETTING: Medical-surgical intensive care unit.
      PATIENTS: 190 patients who were admitted to the intensive care unit during a 33
      month period and whose condition suggested the need for prolonged intubation (> 3
      days). INTERVENTION: 76 patients were randomly allocated to receive continuous
      aspiration of subglottic secretions, and 77 control patients were allocated to
      receive usual care. MEASUREMENTS: The numbers of cases of ventilator-associated
      pneumonia, ventilated days, days in intensive care unit, and deaths were
      recorded. The amount of subglottic secretions aspirated daily and surveillance
      cultures in the subglottic secretions were also obtained periodically. Etiologic
      diagnosis was based on the quantitative culture of secretions obtained by
      protected specimen brush or bronchoalveolar lavage. RESULTS: The incidence rate
      of ventilator-associated pneumonia was 19.9 episodes/1000 ventilator days in the
      patients receiving continuous aspiration of subglottic secretions and 39.6
      episodes/1000 ventilator days in the control patients (relative risk, 1.98; 95%
      CI, 1.03 to 3.82). This difference was due to a significant (P < 0.03) reduction
      in the number of gram-positive cocci and Haemophilus influenzae organisms in the
      patients receiving continuous aspiration. However, no differences were observed
      in the number of Pseudomonas aeruginosa or Enterobacteriaceae organisms. Episodes
      of ventilator-associated pneumonia occurred later in patients receiving
      continuous aspiration (12.0 +/- 7.1 days) than in the control patients (5.9 +/-
      2.1 days) (P = 0.003). The same microorganisms isolated from protected specimen
      brush or bronchoalveolar lavage cultures in patients with ventilator-associated
      pneumonia were previously isolated from cultures of subglottic secretions in 85%
      of cases. No significant differences in outcome were found. CONCLUSIONS: The
      incidence of nosocomial pneumonia in mechanically ventilated patients can be
      significantly reduced by using a simple method that decreases the chronic
      microaspirations through the cuff of endotracheal tubes.

PMID- 7810936
TI  - Estimating the risk for sepsis after splenectomy in hereditary spherocytosis.

PMID- 7810937
TI  - Pituitary tumor hemorrhage in Cushing disease.

PMID- 7810939
TI  - Cardiac pacing for prevention of recurrent vasovagal syncope.
AB  - PURPOSE: To review the status of cardiac pacing for the treatment of patients
      with recurrent vasovagal syncope. DATA SOURCES: A MEDLINE search for English- and
      French-language articles published between 1980 and 1994 about cardiac pacing for
      prevention or treatment of vasovagal syncope. The term cardiac pacing was used in
      conjunction with the terms vasovagal, neurally mediated, or neurocardiogenic
      syncope, but not with the term carotid sinus hypersensitivity. STUDY SELECTION:
      Case reports and series from peer-reviewed journals were selected if they
      documented the presence of vasovagal syncope and assessed pacing effectiveness
      using tilt-table testing, clinical follow-up, or both. Four case reports and four
      series met these criteria. DATA EXTRACTION: Findings were summarized
      individually. Statistical analysis of combined data was inappropriate given
      differences among studies in patient selection, testing, and follow-up. RESULTS:
      Pacing may be useful in selected patients with predominantly cardioinhibitory
      vasovagal responses. Pacing alone may eliminate symptoms in 25% of these patients
      and may prevent abrupt cardiovascular collapse in others (such as those in whom
      syncope occurs with minimal or no premonitory sensation). However, interpretation
      of most available reports has been limited both by the uncertainty associated
      with using the tilt-table technique to assess pacing effectiveness and by
      relatively short-term follow-up. CONCLUSIONS: The usefulness of cardiac pacing
      for patients with recurrent vasovagal syncope remains only partly understood.
      Randomized controlled trials are needed for this and other aspects of the
      treatment of this condition. Additionally, substantial room remains for
      innovation both in earlier recognition of imminent vasovagal syncope by
      implantable devices and in specifically designing cardiac pacing algorithms for
      treatment of this condition.

PMID- 7810938
TI  - The SUPPORT prognostic model. Objective estimates of survival for seriously ill
      hospitalized adults. Study to understand prognoses and preferences for outcomes
      and risks of treatments.
AB  - OBJECTIVE: To develop and validate a prognostic model that estimates survival
      over a 180-day period for seriously ill hospitalized adults (phase I of SUPPORT
      [Study to Understand Prognoses and Preferences for Outcomes and Risks of
      Treatments]) and to compare this model's predictions with those of an existing
      prognostic system and with physicians' independent estimates (SUPPORT phase II).
      DESIGN: Prospective cohort study. SETTING: 5 tertiary care academic centers in
      the United States. PARTICIPANTS: 4301 hospitalized adults were selected for phase
      I according to diagnosis and severity of illness; 4028 patients were evaluated
      from phase II. MEASUREMENTS: A survival model was developed using the following
      predictor variables: diagnosis, age, number of days in the hospital before study
      entry, presence of cancer, neurologic function, and 11 physiologic measures
      recorded on day 3 after study entry. Physicians were interviewed on day 3.
      Patients were followed for survival for 180 days after study entry. RESULTS: The
      area under the receiver-operating characteristics (ROC) curve for prediction of
      surviving 180 days was 0.79 in phase I, 0.78 in the phase II independent
      validation, and 0.78 when the acute physiology score from the APACHE (Acute
      Physiology, Age, Chronic Health Evaluation) III prognostic scoring system was
      substituted for the SUPPORT physiology score. For phase II patients, the SUPPORT
      model had equal discrimination and slightly improved calibration compared with
      physician's estimates. Combining the SUPPORT model with physician's estimates
      improved both predictive accuracy (ROC curve area = 0.82) and the ability to
      identify patients with high probabilities of survival or death. CONCLUSIONS: A
      limited amount of readily available clinical information can provide a foundation
      for long-term survival estimates that are as accurate as physicians' estimates.
      The best survival estimates combine an objective prognosis with a physician's
      clinical estimate.

PMID- 7810940
TI  - Lymphomatoid papulosis: a T-cell dyscrasia with a propensity to transform into
      malignant lymphoma.
AB  - OBJECTIVE: To describe the diagnostic difficulties, response to therapy, and
      clinical features of lymphomatoid papulosis and the cumulative frequency of
      transformation to lymphoma. DESIGN: Case series. SETTING: University hospitals.
      METHODS: The records of 21 patients with lymphomatoid papulosis who were seen
      from 1986 to 1993 were retrieved from the archives of two institutions. The entry
      criteria for the study were lymphomatoid papulosis misdiagnosed at the time of
      original presentation or lymphomatoid papulosis that later developed into
      lymphoma. RESULTS: When lymphomatoid papulosis tissues are pathologically
      examined, they are frequently confused with lymphoma, melanoma, or carcinoma.
      Eight of the 19 patients whose condition was misdiagnosed as malignant received
      either chemotherapy or radiotherapy. Although lymphomatoid papulosis responded to
      cytotoxic chemotherapy, the remissions were transient and promptly recurred after
      or during treatment. However, all five cases that became malignant responded to
      chemotherapy and have not recurred. Five of 21 patients (24%) developed lymphoma,
      but the cumulative risk for transformation after 15 years was 80%. CONCLUSIONS:
      Lymphomatoid papulosis can only be diagnosed accurately through a careful history
      in which the characteristic waxing and waning of the skin lesions is identified
      and through proper communication between clinicians and pathologists. Patients
      with lymphomatoid papulosis have an increased risk for developing lymphoma that
      is much higher than the 15% to 20% quoted in the literature. Patients who develop
      lymphoma respond well to cytotoxic chemotherapy and can be cured with appropriate
      therapy. Internists and oncologists need to be aware of lymphomatoid papulosis
      and its characteristic clinical features so that this disorder is accurately
      diagnosed and so that unnecessary and potentially hazardous treatment is avoided.

PMID- 7810941
TI  - Host-directed and immune-based therapies for human immunodeficiency virus
      infection.
AB  - This essay reviews the rationale underlying host-directed or immune-based
      therapeutic strategies for human immunodeficiency virus (HIV) infection and its
      complications. These approaches have seen only limited trial in the past 10
      years, but as more is learned about the immunopathogenesis of HIV disease and as
      the limitations of virus-directed therapies become more apparent, the need to
      pursue other therapeutic avenues has become increasingly important. Moreover,
      properly designed trials of host-directed and immune-based therapies can provide
      key insights into the pathogenesis of HIV disease that may be otherwise
      unattainable through in vitro studies.

PMID- 7810942
TI  - The efficacy and safety of diuretics in treating hypertension.
AB  - The efficacy of thiazides and related diuretics in preventing most of the
      complications of hypertension has been conclusively documented in long-term
      controlled trials. Among their adverse effects, thiazides may induce a short-term
      increase in serum cholesterol levels. However, the elevation returns to
      pretreatment levels during long-term therapy. In addition, long-term treatment
      with thiazides is not associated with an elevation of blood glucose levels or an
      increased incidence of diabetes. Because the long-term controlled trials have
      shown that thiazides provide more protection against stroke than against coronary
      heart disease events, it is possible that the difference may be caused by adverse
      effects of the diuretics. In three of four recent trials that used low doses of
      thiazides plus potassium-sparing diuretics, the number of sudden deaths was
      reduced more than in other trials that used high doses of diuretics alone. A
      recent case-control study also found that small doses of diuretics combined with
      potassium-sparing drugs were associated with a reduced number of sudden deaths
      compared with high doses used alone. Although these results suggest that small
      doses reduce the risk for sudden death more than do large doses, they cannot be
      regarded as conclusive. A randomized double-blind trial comparing low and high
      doses of thiazide diuretics and potassium-sparing drugs must be done. For now,
      however, small doses seem prudent for treating hypertension.

PMID- 7810943
TI  - Hepatitis C genotypes: the key to pathogenicity?

PMID- 7810944
TI  - Prevention of hospital-acquired pneumonia: measuring effect in ounces, pounds,
      and tons.

PMID- 7810945
TI  - Clinical research in the acquired immunodeficiency syndrome.

PMID- 7810946
TI  - Stroke prevention guidelines.

PMID- 7810947
TI  - Omeprazole therapy in resistant reflux disease.

PMID- 7810948
TI  - Omeprazole, serum gastrin, and gastric acid suppression.

PMID- 7810949
TI  - Urinary tract infection with Enterococcus faecalis.

PMID- 7810950
TI  - Use of vascularized corticoperiosteal flap from the femur for reconstruction of
      the orbit.
AB  - The reconstruction of small and thin defects in the orbital area using
      vascularized cortex is described herein. This vascularized cortex is taken from
      the medial supracondyle area of the femur because a small, thin, and flexible
      bone can be harvested. We have treated 5 patients with orbital bony defects that
      would have been difficult to reconstruct using conventional free bone grafts. All
      flaps took perfectly, the results were satisfactory, and no functional loss
      occurred in the donor site. The advantages of this bone flap include rich
      vascularity, a long vascular pedicle of about 7 cm, easy flap elevation, and the
      ability to include a saphenous flap. The thinness and flexibility of the bone
      flap make it a suitable vascularized bone donor site for treating small, flat
      craniofacial bony defects such as in the orbital area.

PMID- 7810951
TI  - Oromandibular reconstruction using a keel-shaped modification of the radial
      forearm osteocutaneous flap.
AB  - The keel-shaped modification for harvest of the radial forearm osteocutaneous
      flap has been used to reconstruct 19 oromandibular defects in 18 patients.
      Fourteen men and 4 women ranging in age from 22 to 72 years have undergone
      composite mandibular reconstruction, with follow-up ranging from 3 to 36 months.
      Sixteen patients (17 reconstructions) had resection of advanced malignancies, and
      2 patients sustained shotgun wounds. Twelve symphyseal and 7 lateral or posterior
      defects were reconstructed with donor radius bone ranging in length from 5 to
      13.5 cm. Double osteotomies were performed in 7 patients. Two skin paddles were
      used in 4 patients to provide simultaneous intraoral lining and external skin
      coverage. The radial forearm osteocutaneous flap is still an excellent choice for
      oromandibular reconstruction. Anterior and lateral composite mandibular defects
      were satisfactorily reconstructed both aesthetically and functionally using the
      keel-shaped modification of the radial forearm flap. Donor-site problems were
      uncommon and minor, and long-term forearm function was minimally affected. Radius
      fracture occurred in only 1 patient.

PMID- 7810952
TI  - Histomorphology of neochondrogenesis after antihelical fold creation: a
      comparison of three otoplasty techniques in the rabbit.
AB  - The purpose of this article is twofold: (1) to investigate the histomorphology of
      cartilaginous proliferation using three different otoplasty techniques and (2) to
      determine whether recurrence is related either to the method of otoplasty or the
      duration of suture fixation. Eighteen 6-week-old New Zealand white rabbits were
      divided into three equal groups. In each animal, a skin pocket was developed on
      the posterior surface of both ears; the perichondrium of the left ear was
      stripped off, whereas the perichondrium of the right ear was left undisturbed.
      Otoplasties were performed by inserting permanent mattress sutures with (Converse
      Wood-Smith) or without (Mustarde) cartilaginous incisions or by scoring of the
      anterior cartilaginous surface of the antihelix (Stenstrom). In each group,
      sutures were cut at 1, 2, 4, and 6 weeks and the animals killed 1 week later.
      Histomorphometric analysis was performed. Perichondrial stripping stimulated
      cartilaginous proliferation in all groups. The antihelical fold maintained its
      shape best in group 3, in which the anterior perichondrium was rasped; a
      fibrocartilaginous cap formed over the rasped convex surface of the antihelical
      fold, reinforcing and stabilizing the newly created fold. Groups 1 and 2, in
      contrast, demonstrated significantly less anterior cartilaginous proliferation
      than did group 3, and cap formation was not observed. No significant differences
      were apparent between groups 1 and 2 in either the quantity or quality of
      cartilaginous proliferation in any of the time periods. Cutting the sutures at 1
      week resulted in loss of shape or "flattening" of the fold in all groups;
      however, increased cartilaginous proliferation between 2 and 6 weeks stabilized
      the fold, minimizing deformability.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7810953
TI  - Orbital venous approach to the cavernous sinus: an analysis of the facial and
      orbital venous system.
AB  - Carotid-cavernous fistulas are abnormal communications between the internal
      carotid artery and the cavernous sinus produced by a rupture of the wall of the
      carotid artery or one of its branches into the sinus. Extradural branches of the
      internal or external carotid arteries may communicate with the cavernous sinus,
      producing proptosis, progressive glaucoma, and ocular vascular engorgement.
      Various approaches to obliterate these fistulas have evolved, many of which carry
      high morbidity or are precluded by anatomical considerations. Analysis of the
      venous anatomy of the orbit and face, including human cadaver dissections,
      reveals a new and safe approach to the cavernous sinus, requiring microsurgical
      isolation and cannulation of the superior ophthalmic vein through an anterior
      orbital approach. Selective embolization of a carotid-cavernous fistula can be
      performed successfully through this route. We present pertinent anatomy and
      technical considerations and the successful clinical application of these
      principles. Surgeons familiar with craniofacial anatomy and microvascular
      techniques can apply these principles and play an active role in the treatment of
      these complex problems.

PMID- 7810954
TI  - Grafting of autologous-cultured epithelium after excision of tattoos.
AB  - Nine patients with tattoos were treated with cultured epidermal autografts. The
      tattoos were excised down to the deep dermal layer, and the wounds were covered
      with cultured epidermal autografts. The areas grafted with cultured epidermal
      autografts were an average of 907 cm2 in size. The average percentage "take" of
      the cultured epidermal autografts was 86%. The average time for complete wound
      epithelialization was 20 days. The pain at the grafted sites was minimal. There
      was minimal scarring and no tendency for scar contracture. The appearance and
      elasticity of the grafted sites resembled those of adjacent normal skin 2 1/2
      years after grafting. These findings demonstrate that cultured epithelium
      autografting is a suitable method for coverage of the tangentially excised tattoo
      wound.

PMID- 7810955
TI  - Is bed isolation necessary during flap prefabrication? An experimental study in
      rats.
AB  - This study was designed to investigate whether isolation of the bed is necessary
      during flap prefabrication. A fasciovascular carrier was used to prefabricate a 3
      x 8-cm epigastric flap in rats. The animals were divided into three groups of 42
      each. During flap prefabrication, in group 1 (control), no bed isolation was
      done, whereas in groups 2 and 3, a thin silicone sheet was used to isolate the
      underlying bed from the flap and fasciovascular carrier partially or completely,
      respectively. In each group, 14 prefabricated flaps were raised at 3, 7, and 14
      days after prefabrication. Flap survival was assessed at day 7 after flap
      elevation. In comparing to the survival rates of the prefabricated flaps for each
      time interval, there was no significant statistical difference between the
      control and experimental groups (p > 0.05). With further studies, including india
      ink injection study and microangiographical and histological examinations of the
      prefabricated flaps, it was concluded that, during flap prefabrication, isolation
      of the bed with a silicone sheet does not improve the survival of prefabricated
      skin flaps. Moreover, it may cause some complications, such as extensive seroma,
      infection, and exposure of the sheet, which further interfere with the evaluation
      of experimental results.

PMID- 7810956
TI  - Inhibition of human keloid fibroblast growth by isotretinoin and triamcinolone
      acetonide in vitro.
AB  - In this study, we evaluated the effects of isotretinoin and triamcinolone
      acetonide on the growth of keloid and embryonal human skin fibroblasts in vitro.
      Culture bottles were plated with 2 x 10(5) cells and after 3 days of growth in
      Eagle's minimum essential medium, the medium was changed to one containing the
      drug being evaluated. Five groups were established: (1) regular medium as the
      control; (2) the medium containing 0.1% ethyl alcohol (the vehicle in which
      isotretinoin is dissolved); (3) the medium containing isotretinoin; (4) the
      medium containing triamcinolone acetonide; (5) the medium containing both drugs.
      Our study demonstrated that isotretinoin and triamcinolone acetonide each
      significantly inhibited the growth of the cells, and the effect of the
      combination was greater than that of either drug used alone.

PMID- 7810957
TI  - Experimental study of microarterial autografts for repair of arterial defects
      with significant size discrepancy.
AB  - On the basis of our years of clinical experience using the "unequal bite"
      suturing technique to perform end-to-end anastomosis of vessel with great
      discrepancy in diameter, an animal experimental study was performed in which an
      arterial defect, 1.0 to 1.4 mm in diameter, was reunited through the autogenous
      arterial graft, which was 0.3 to 0.4 mm in diameter. A high patency rate (95% in
      total) was obtained postoperatively. A small autogenous arterial graft may be
      used for repairing a large-caliber arterial defect clinically.

PMID- 7810958
TI  - Mammographic and sonographic findings after silicone injection.
AB  - The illicit use of silicone injection for cosmetic augmentation was performed in
      the 1960s. However, this method of augmentation was subsequently abandoned.
      Recently, a resurgence of this practice has occurred. We present reports of 2
      patients who had non-medical-grade silicone injected into their breasts
      clandestinely. The clinical findings and imaging features are presented.

PMID- 7810959
TI  - Bilateral simultaneous groin flaps in the salvage of a pediatric blast-injured
      hand.
AB  - The groin flap was first described by McGregor and Jackson in 1972. Since then it
      has been applied to a wide variety of reconstructive problems. The flap is
      amenable to both staged and free tissue transfer and can provide cutaneous or
      composite tissues. However, use of this flap in the pediatric population has been
      limited. We herein describe the first known case of simultaneous bilateral staged
      groin flaps for salvage of a blast-injured hand in a child.

PMID- 7810960
TI  - Divided latissimus dorsi musculocutaneous flap for chest wall radionecrosis.
AB  - A 69-year-old woman with a history of mastectomy and radiotherapy for breast
      carcinoma demonstrated extensive anterior thoracic wall radionecrosis 22 years
      later. The latissimus dorsi musculocutaneous flap was chosen to repair two
      distant ulcerative defects. Chest wall coverage was performed by dividing the
      muscle into two separate musculocutaneous flaps. Results were particularly
      promising 6 months after surgery.

PMID- 7810961
TI  - Combined anteroposterior tibial perforator-based flap with a vascularized deep
      peroneal nerve for repair of facial defect.
AB  - To reconstruct deep facial defects involving the facial nerves after resection of
      a malignant parotid tumor, a flap with a vascularized nerve graft is often
      required because the lesion is often accompanied by poor vascularization as a
      result of preoperative or postoperative radiotherapy. These defects can be
      repaired in one stage with a combined anteroposterior tibial perforator-based
      flap including a vascularized deep peroneal nerve graft. This combined flap can
      include the long vascularized deep peroneal nerve, and augumentation of the lower
      leg flaps is possible by additional vascular anastomosis of branches of the
      source vessel of the neighboring flap, the "mosaic" principle.

PMID- 7810962
TI  - Benign "metastatic" cellular blue nevus.
AB  - This report illustrates the case of a patient with a pigmented lesion on the
      dorsal skin of his left foot associated with a bulky homolateral inguinal mass. A
      metastatic melanoma was clinically suspected; therefore, the pigmented foot
      lesion was excised and grafted, and the groin mass was dissected. The
      histological examination of the foot lesion revealed a well-preserved epidermal
      layer, beneath which spindle cells endowed with regular nuclei yet without any
      atypia or mitotic figures, were present. Melanin-rich histiocytes surrounded the
      nerve fibers and the vessels that intermingled with such spindle cells. Under
      light microscopy, the sections of the inguinal lymph nodes revealed clusters of
      pigmented cells that looked very much like those found in the foot skin lesion.
      These spindle-shaped cells infiltrated the nodes' capsule and peripheral sinuses
      and left the inner parenchyma unaltered. The inguinal mass revealed a thick,
      fibrous capsule surrounding a heavily pigmented tissue rich with blue nevus cells
      with islands of melanophages. In the case presented here, the differential
      diagnosis between cellular blue nevus and nodular melanoma was mandatory. In this
      case report, we provide the differential diagnosis and review the criteria used
      for it. Further support for the diagnosis was obtained from immunohistochemical
      findings that were positive for S-100 protein and not for HMB-45. Wide but
      conservative surgery appears to be the treatment of choice for cellular blue
      nevus. In fact, the patient described here is still alive 5 years
      postoperatively. Hence, the clinical evolution of the patient's lesions can be
      considered benign.

PMID- 7810963
TI  - Intramuscular ganglion of the biceps muscle.
AB  - Ganglia are reported to have arisen in association with bursa or connected to
      synovial joints. We report a patient with a ganglion within the biceps muscle
      most likely to have evolved from an embryological arrest.

PMID- 7810964
TI  - Release of acquired syndactylies in Kindler syndrome.
AB  - Kindler syndrome is a rare, blistering skin disease characterized by acral
      bullae, poikiloderma, and diffuse cutaneous atrophy. Kindler syndrome has been
      established as a separate entity from epidermolysis bullosa; however, controversy
      still remains as to whether Kindler syndrome can be differentiated from Weary's
      hereditary acrokeratotic poikiloderma. Fusion of the digits secondary to
      blistering and scarring, "pseudosyndactyly," has been reported in several
      patients with Kindler syndrome; however, surgical correction of the syndactylies
      in these patients has not been described. In this report, a patient with Kindler
      syndrome underwent surgical treatment of acquired syndactylies. Treatment
      included a tailored approach to preparation of the patient for surgery, surgical
      separation of fused tissues, selection of donor site for skin-graft harvest,
      postoperative dressings, splinting, and therapy. Results in our patient 2 years
      after correction demonstrate that syndactyly release in Kindler syndrome can be
      accomplished effectively, with improvement in both function and appearance.

PMID- 7810965
TI  - Adipofascial turnover flap for facial contour deformity during parotidectomy.
AB  - An adipofascial turnover flap is described. This vascularized flap is technically
      simple to perform and provides excellent cosmetic results for patients with a
      very large tumor undergoing superficial parotidectomy. The flap also acts as a
      barrier for regenerating nerves, preventing the development of gustatory
      sweating.

PMID- 7810966
TI  - Management of facial fractures in children and adolescents.
AB  - The surgical management of facial fractures in children has evolved gradually.
      Children sustaining facial fractures have not benefited equally as their adult
      counterparts from the rapid refinements in the management of facial trauma. Only
      recently have the distinct advantages of accurate primary repair of facial
      fractures been applied to the rehabilitation of the injured child. The pattern of
      craniomaxillofacial fractures seen in children and adolescents varies with their
      evolving skeletal anatomy and socioenvironmental factors. A personal philosophy
      for the effective management of the craniomaxillofacial injuries that tend to
      occur in facially traumatized children and adolescents is reviewed.

PMID- 7810967
TI  - Tom's rule.

PMID- 7810968
TI  - Re: The use of expanded polytetrafluoroethylene as a permanent filler and
      enhancer: an early report of experience.

PMID- 7810969
TI  - Re: Extended anterior thigh flaps for repair of massive cervical defects
      involving pharyngoesophagus and skin: an introduction to the "mosaic" flap
      principle.

PMID- 7810970
TI  - Re: Factors affecting the rupture of silicone-gel breast implants.

PMID- 7810971
TI  - [Role of plastic and reconstructive surgery in cancerology].

PMID- 7810972
TI  - [Reconstruction with free jejunal graft after pharyngo-esophageal resection for
      cancer: functional results and survival].
AB  - 57 patients with cancer of the hypopharynx underwent 59 pharyngo-esophageal
      reconstructions with a free jejunal graft after total removal of a tumor combined
      with resection of the circumferential tissues. 18 patients had been previously
      irradiated. Median resumption of oral intake was 16 days; 40 out of 50 patients
      (98%) followed for more than 2 years regained normal eating habits. The
      cumulative 5-year survival rate was 44%. The free jejunal graft should be
      advocated as a safe and reliable procedure for hypopharyngeal cancer.

PMID- 7810973
TI  - [Rectovaginal fistulas in adults].
AB  - Recto-vaginal fistulas have multiple causes and a wide range of clinical and
      anatomical features. Simple fistulas, defined by a low situation, a traumatic
      origin, and a small size are accessible to simple means of cure. They can be
      operated from a vaginal approach, with conversion into a third degree perineal
      tear followed by repair of the perineal body, and the anal canal; they can be
      managed from a transanal approach, using endorectal flap advancement technique.
      Complex fistulas, defined by the etiology (IBD, radiation enteritis, cancer,
      postoperative), a high situation, or a large size, require larger and more
      sophisticated operations such as a combined abdomino-perineal approach or a
      muscle flap technique. Among the numerous techniques described for the cure of
      recto-vaginal fistulas, the authors emphasize those currently used by the most
      experienced teams of colo-rectal or gynecological surgeons.

PMID- 7810974
TI  - [Contribution of the artificial pancreas in the diagnosis and surgical treatment
      of insulinomas].
AB  - Insulinomas are often hard to diagnose and difficult to locate during surgery. We
      tested the contribution of artificial pancreas (AP) for case management of our
      last eight patients including two cases with multiple insulinomas. When diagnosis
      is uncertain, the euglycemic hyperinsulinic clamp technique under AP is a safe
      method to assess inappropriate insulin secretion characterized by a high plasma
      level of C peptide not inhibited by insulin injection. During surgery the AP
      provides a feed back controlled glucose infusion and thus maintains blood glucose
      above a predefined level. It allows a safe operation, preventing sudden
      hypoglycemia. By providing continuous data about intensity of glucose infusion
      and blood glucose, it helps to detect an occult secreting tumor (a preoperative
      therapeutic test with diazoxide requires stopping treatment for at least one
      month before surgery to avoid false negative results) and confirms the total
      ablation of abnormal insulin-producing cells. Peroperative monitoring curves of
      glucose infusion and blood glucose related to exploration and ablation procedures
      illustrate the contribution of this method in helping surgical treatment which
      can be perfectly adapted to the lesions as shown by the total recovery of our
      eight patients (mean follow-up: 43.2 months).

PMID- 7810975
TI  - [Comparative secretory profiles of benign and malignant pheochromocytomas].
AB  - Distant metastases are the only clue for diagnosis of malignancy in
      pheochromocytoma patients. This study was designed to define a secretory profile
      possibly suggestive of malignancy. Among 79 pheochromocytomas (55 benign, 24
      malignant), dopamine-secretion, either exclusive or blended with other
      catecholamines was found in 34.5% of benign and in 75% of malignant tumors.
      Dopamine secretion, although if more frequent and more abundant in cases of
      malignant pheochromocytomas, is therefore not actually diagnostic, but only
      suggestive of malignancy. It demands life-long follow-up as metachronous
      metastases may supervene extremely late in the course of the disease.

PMID- 7810976
TI  - [Role of laparoscopy in the current treatment of lithiasis of the common bile
      duct. Apropos of 63 cases of lithiasis].
AB  - The purpose of this study is to evaluate the operative technique, indications and
      results of laparoscopic management of common bile duct (CBP) stones. While
      laparoscopic cholecystectomy has become the procedure of choice for gallstones,
      the management of CBD stones remains controversial. From October 1989 to may
      1993, we performed 634 cholecystectomies, 615 of them carried out by laparoscopy,
      (97%). We found 63 cases of CBD stones (9.9%). At the beginning, CBD stones were
      managed either by endoscopic sphincterotomy (12 cas) or by laparotomy (6 cas). We
      subsequently performed laparoscopic treatment of CBD stones. Forty-six patients
      have been treated in this way: 17 via a transcystic approach successfully in 14
      cases (82.3%) and 29 by choledochotomy with 27 successful extractions (93.1%).
      There was no mortality and a morbidity of 4.3% (1 retained stone and 1 wound
      infection). Endoscopic sphincterotomy is indicated in high risk elderly patients
      and in complicated stones. (pancreatitis cholangitis), while the whereas
      incidence of open surgery is greatly reduced; the advantages of laparoscopic
      management of CD stones are its noninvasive aspect and the complete clearance of
      the stones in one operation.

PMID- 7810977
TI  - [Treatments of biliary fistulas following the removal of a Kehr tube after
      orthotopic liver transplantation].
AB  - Biliary tract complications are a major source of morbidity after liver
      transplantation. From October 1990 to September 1992, 77 patients, including 13
      children and 64 adults, received 80 liver transplants. Biliary reconstruction was
      performed using a choledochocholedochostomy with a T-tube in 40 recipients. We
      report the management of bile leaks following T tube removal in 6 patients. In
      all cases, bile leak was diagnose by ultrasound examination requested for
      abdominal pain. In the first 2 patients, a surgical treatment was applied: Roux
      en-Y choledochojejunostomy was performed on the first patient and simple suture
      of the fistula in the second patient. Two patients were managed nonoperatively
      using endoscopic and radiological procedures allowing placement of bile duct
      prosthesis and abdominal drainage. In 2 patients with small localized sub-hepatic
      collection, no surgical or radio-endoscopic treatment was attempted; spontaneous
      resolution of the collections was achieved in 2 months on ultrasound examination.
      All patients are alive, although, the patient who was operated on with a roux-en
      Y choledochojejunostomy developed thrombosis of the right hepatic artery and
      biliary anastomotic stenosis which required further operations. We advocate
      endoscopic placement of endobiliary prosthesis and percutaneous biliary drainage
      as first-line therapy for significant fistula after T-tube removal. The use of
      choledochocholedochostomy without a T-tube when possible for biliary
      reconstruction in liver transplantation could be an effective procedure, but
      requires further evaluation.

PMID- 7810978
TI  - [Leiomyomas of the lower third of the esophagus. Value of transhiatal
      enucleation].
AB  - Leiomyomas are the common est benign tumors of the esophagus and most of them are
      located in the lower third. Dysphagia and vague pain are the most frequent
      symptoms. However, 50% of the patients remain asymptomatic and the tumor is often
      discovered incidentally. Operative management by transthoracic enucleation is the
      procedure of choice but for asymptomatic forms, this remains controversial. In
      addition, gastro-esophageal reflux frequently coexists with an esophageal
      leiomyoma and the therapeutic indications are not well defined for such
      situations. We report 3 cases of esophageal leiomyoma situated in the lower
      third, with emphasis on the operative management by transhiatal enucleation,
      particularly in case of coexisting gastro-esophageal reflux. This procedure
      avoids thoracotomy and the surgical treatment of the associated gastro-esophageal
      reflux is much easier by this approach than with thoracotomy.

PMID- 7810979
TI  - [Anatomic pitfalls of vagotomies].
AB  - In order to minimise relapses and functional problems after vagotomies, an
      anatomic study of the vagus nerve at the base of the esophagus and stomach was
      carried out. Fifty stomachs of adult black African corpses were collected, placed
      in a formaldehyde solution and then dissected. At the level of the esophageal
      hiatus, the trunks of the vagus nerve were found in 46% of the cases for the
      anterior vagus and 24% for the posterior. At the level of the abdominal esophagus
      there was a single anterior vagus in 68% of cases and single posterior vagus in
      64% of cases. At the level of the greater curvature, a recurrent anterior branch
      was found. At the level of the lesser curvature, the main nerves had a plexiform
      appearance in 8% of cases for the anterior nerve and 6% of cases for the
      posterior nerve. The classical arrangement was found in 60% of cases for the main
      anterior nerve and 64% of the cases for the posterior nerve. At the level of the
      angulus, the classical crowsfeet was found in 20% of cases for the anterior vagus
      and in 32% of cases for the posterior vagus. The anterior vagus was plexiform in
      54% of cases and 46% of cases for the posterior. This study confirms the extreme
      variability of the vagus in the stomach. A better knowledge of the variations
      should lead to more successful vagotomy regardless of its forms.

PMID- 7810980
TI  - [Surgical training in Switzerland].
AB  - The training protocol for Swiss surgeons has become obsolete and too many new
      surgeons are being granted specialist diplomas. A revision of surgical training
      will have to take into account increasing patient demands, the multidisciplinary
      nature of treatments, and rapid progress in surgical techniques. It should allow
      the possibility of earlier specialization within the field of general surgery,
      but reserved to those surgeons who will remain in major hospital centres in the
      long term. It will have to integrate surgical research activities and recognize
      them as part of training. The introduction of examinations is essential to
      establish equivalencies with European countries and to ensure an identical level
      of training in all countries. This restoration of objective competitiveness will
      help to control the plethora of surgeons and the decreased number of active
      surgeons will help to group patients in a hospital system readjusted to needs and
      to current costs.

PMID- 7810981
TI  - [Value of CT scan in the diagnosis of small pneumoperitoneum].
AB  - This case-report concerns a small pneumoperitoneum not demonstrated on plain
      radiographs and detected on CT scan. The patient had a blunt abdominal trauma
      with jejunal perforation. The performances of CT compared to other investigations
      in traumatic intestinal injuries are analysed.

PMID- 7810982
TI  - [Acute obstruction of the esophagus by mucilage followed by perforation. Apropos
      of a case].
AB  - The authors report an iatrogenic case of lower esophageal perforation which
      occurred after a Heimlich procedure performed for a acute drug-induced
      oesophageal obstruction (mucilage). Esophageal repair, drainage and Nissen
      procedure to prevent gastro-esophageal reflux were successfully performed via an
      abdominal approach.

PMID- 7810983
TI  - [Torsion of a hydatid cyst of the peritoneum].

PMID- 7810984
TI  - Resistance to avermectins: extent, mechanisms, and management implications.
AB  - The avermectins represent a group of natural compounds with potent pesticidal
      activities. Because of their novel mode of action, they represent an important
      resource for pest control and resistance management. In the Colorado potato
      beetle, the house fly, and the two-spotted spider mite, resistance to abamectin
      is usually autosomal, recessive, and polygenic. Although these aspects are
      beneficial in resistance management, the fact that resistance could be readily
      selected for suggests that abamectin needs to be used in moderation. Furthermore,
      several major resistance mechanisms (e.g. excretion, oxidative metabolism,
      penetration) and minor factors (e.g. altered target site, conjugation,
      hydrolysis/sequestration) have been implicated in abamectin resistance. Thus, the
      question is not whether resistance to abamectin will occur but is simply when and
      how it will occur. To address this problem, we have gathered information on the
      genetics, biochemical mechanisms, effectiveness of synergists, and cross
      resistances to other insecticides from three abamectin-resistant insects.
      Judicious implementation of this information may prove useful in the resistance
      management of this natural pesticide.

PMID- 7810985
TI  - Molecular mechanisms of action of juvenile hormone.
AB  - Determination of the molecular modes of action of juvenile hormone to regulate
      gene expression has remained an elusive goal. This review discusses how studies
      on JH action have been influenced by the perspectives based on the mode of action
      of vertebrate retinoid/steroid hormones. Also identified are assumptions implicit
      in the experimental approaches used thus far, as well as alternative perspectives
      from which to frame future hypotheses on JH action.

PMID- 7810986
TI  - Malaria: current and future prospects for control.
AB  - Malaria is the most important insect-transmitted human disease, but progress in
      its control has been slow, especially in Africa where approximately 90% of the
      infections occur. Several factors have contributed to the problem. Parasites and
      vectors have developed resistance to antimalarial drugs and insecticides;
      differences in the biology of major malaria vectors preclude the development of
      simple, universally applicable strategies for malaria control; and the cost of
      available malaria-control tools often exceeds the public health resources in the
      most malarious parts of the world. New tools are desperately needed. Current
      efforts include the testing of tools such as insecticide-impregnated bed nets
      that could become available in the near term, as well as long-term projects such
      as the development of malaria vaccines and mosquito-targeted genetic control
      strategies. The success or failure of any of these approaches will depend
      ultimately on understanding the natural patterns of malaria transmission in the
      field.

PMID- 7810987
TI  - Cellular and molecular interrelationships between ticks and prokaryotic tick
      borne pathogens.
AB  - Tick-borne prokaryotic pathogens share a very intimate relationship with the
      vectors. Ingestion during the bloodmeal places the microbe into the gut lumen
      whence it must travel to the salivary glands at the right time for transmission
      during a subsequent feeding. This crucial event requires coordination between
      pathogen development and arthropod host activities that may be mediated by the
      expression of genes specific for the vector phase of the pathogen. Invertebrate
      hormones or factors associated with tick tissues may provide the cues that signal
      changes in tick physiology that induce necessary steps in the pathogen, such as
      colonization of ovaries during egg development in preparation for transovarial
      transmission or dispersion to the salivary glands at the time of a bloodmeal.
      These hypotheses cannot easily be investigated within the complex environment of
      the tick, but tick cell culture offers a simplified system with which to examine
      many of these important interrelationships.

PMID- 7810988
TI  - Tick salivary gland physiology.
AB  - The multifunctional, morphologically complex salivary glands are essential to the
      biological success of ticks and are intricately involved in the transmission of
      pathogens. They are innervated, and there is convincing evidence that dopamine is
      a neurotransmitter at the neuroeffector junction controlling fluid secretion. As
      feeding progresses, the rate of salivary fluid secretion increases greatly,
      enabling the ixodid tick to concentrate the bloodmeal by returning excess water
      and ions to the host. Saliva in feeding ticks is rich in bioactive components and
      exhibits a range of pharmacological properties. Factors identified in saliva or
      salivary glands include cement to help anchor the mouthparts to the host, various
      enzymes and inhibitors, histamine agonists and antagonists, prostaglandins,
      antihemostatic factors, and immuno-modulating factors. A secretion from the
      salivary glands allows ticks to absorb water from the air during the lengthy
      periods off their hosts. The physiology of this remarkable organ provides a
      striking example of strategies that have evolved to meet the challenge of a
      unique parasitic life style.

PMID- 7810989
TI  - Immunological basis for compatibility in parasitoid-host relationships.
AB  - The insect immune system serves as a key defense against attack by parasitoids.
      Incompatible hosts often eliminate parasitoids by encapsulation, a process in
      which hemocytes form a multilayered envelope around the invading organism.
      Capsule formation involves cooperation between one or more classes of hemocytes
      and is likely mediated by cytokines and adhesion molecules. Reciprocally,
      parasitoids have evolved a variety of strategies for overcoming host immune
      responses. Some parasitoids passively avoid elimination by developing in
      locations inaccessible to host hemocytes or by possessing surface features that
      fail to elicit an immune response. Other species actively disrupt the host immune
      system by injecting specific factors into the host at oviposition. In particular,
      polydnaviruses associated with several taxa of parasitoids disrupt capsule
      formation by killing hemocytes or altering their ability to adhere to foreign
      surfaces. These symbionts have likely played a critical role in evolution of host
      range and in defining parasitoid-host compatibility.

PMID- 7810990
TI  - Molecular genetic manipulation of mosquito vectors.
AB  - Despite their central role in disease transmission, relatively little is known of
      the molecular biology of arthropod vectors. Modern molecular approaches will
      undoubtedly provide considerable information about gene regulation and expression
      in vectors and consequently a much better understanding of the biology and
      molecular biology of vectors. Such knowledge is essential for developing
      effective control strategies for vector-borne diseases. In this review, we focus
      upon techniques and approaches used at the Arthropod-Borne and Infectious
      Diseases Laboratory (AIDL) at Colorado State University to bioengineer mosquitoes
      with reduced vector competence. We have developed technologies and procedures
      that allow genetic manipulation of mosquitoes, including RNA and DNA virus gene
      delivery vehicles and efficacious antiviral constructs, which will facilitate the
      development of pathogen-resistant, transformed mosquitoes. Many of the
      approaches, constructs, and technologies developed at AIDL will be applicable to
      molecular manipulation of other arthropod genomes.

PMID- 7810991
TI  - Mosquito sugar feeding and reproductive energetics.
AB  - Sugar feeding is a fundamental characteristic of mosquito life. Most evidence
      indicates frequent ingestion by both sexes and all ages of mosquitoes of plant
      sugar, usually as floral and extrafloral nectar and honeydew. Energetically,
      sugar and blood are interchangeable; females of some species have evolved
      independence from one or the other, but most need blood to develop eggs and sugar
      to survive, to fly, and to enhance reproduction. Mosquitoes' commitment to sugar
      is further illustrated by a wealth of behavioral, structural, and physiological
      specializations for finding, feeding on, and processing it. Blood and sugar
      feeding activities are antagonistic and mutually exclusive, owing to conflicting
      demands, yet they support the same goals and often share the same activity
      period. The rules by which females make food-choice decisions have been
      inadequately explored, and we still lack convincing evidence that sugar
      availability in nature varies sufficiently to affect mosquito populations.

PMID- 7810992
TI  - Antimicrobial susceptibility and therapy of infections caused by Chlamydia
      pneumoniae.

PMID- 7810993
TI  - Evolution of susceptibilities of Campylobacter spp. to quinolones and macrolides.
AB  - Erythromycin, new macrolides, and quinolones are alternatives for the treatment
      of Campylobacter infections. Concerns related to the emergence of resistance to
      both groups of drugs have been raised. We studied the evolution of antimicrobial
      susceptibilities of 275 clinical isolates of microorganisms of the genus
      Campylobacter isolated in our institution during a 5-year period (1988 to 1992).
      The microorganisms studied were C. jejuni (n = 230), C. coli (n = 42), and C.
      fetus (n = 3). The overall resistance rates (determined by the agar dilution
      method and the recommendations of the National Committee for Clinical Laboratory
      Standards) were as follows: erythromycin, 2.3%; clarithromycin, 2.3%;
      azithromycin, 1.9%; ciprofloxacin, 28.5%; norfloxacin, 31%; ofloxacin, 26.3%; and
      nalidixic acid, 36.8%. The evolution of resistance (percent resistance in 1988
      versus percent resistance in 1992) was as follows: erythromycin, 2.6 versus 3.1;
      clarithromycin, 2.6 versus 3.1; azithromycin, 2.6 versus 3.1; ciprofloxacin, 0
      versus 49.5; norfloxacin, 2.6 versus 55.5; ofloxacin, 0 versus 45.6; nalidixic
      acid, 2.6 versus 56.8. Our data show stable macrolide activity against
      Campylobacter spp. and the rapid development of quinolone resistance over the
      last 5 years.

PMID- 7810994
TI  - Characterization of the chromosomal aac(6')-Ij gene of Acinetobacter sp. 13 and
      the aac(6')-Ih plasmid gene of Acinetobacter baumannii.
AB  - The amikacin resistance genes aac(6')-Ih of Acinetobacter baumannii BM2686 and
      aac(6')-Ij of Acinetobacter sp. 13 BM2689 encoding aminoglycoside 6'-N
      acetyltransferases were characterized. The 441-bp coding sequences predict
      proteins with calculated masses of 16,698 and 16,677 Da, respectively. Analysis
      of the deduced amino acid sequences indicated that the proteins belonged to a
      subfamily of 6'-aminoglycoside acetyltransferase type I enzymes from gram
      negative bacteria. The aac(6')-Ih gene of BM2686 was located on a 13.7-kb
      nonconjugative plasmid. The aac(6')-Ij gene from BM2689 was not transferable
      either by conjugation to Escherichia coli or A. baumannii or by transformation to
      Acinetobacter calcoaceticus. Plasmid DNA from BM2689 did not hybridize with an
      intragenic aac(6')-Ij probe. These results suggest a chromosomal location for
      this gene. The aac(6')-Ij gene was detected by DNA hybridization in all 28
      strains of Acinetobacter sp. 13 tested but not in other Acinetobacter strains,
      including A. baumannii, proteolytic genospecies 4, 6, 14, 15, 16, and 17, and
      ungrouped strains. The aac(6')-Ih and -Ij probes did not hybridize in dot blot
      assays with DNA from members of the families Enterobacteriaceae and
      Pseudomonadaceae that produced 6'-N-acetyltransferases. These data suggest that
      the genes are confined to the Acinetobacter genus and that the aac(6')-Ij gene is
      species specific and may be used to identify Acinetobacter sp. 13.

PMID- 7810995
TI  - Selective inhibition of topoisomerases from Pneumocystis carinii compared with
      that of topoisomerases from mammalian cells.
AB  - Type I and II topoisomerase activities were partially purified from Pneumocystis
      carinii. The catalytic (strand-passing) activities of both enzymes were
      selectively inhibited by members of a series of dicationic-substituted bis
      benzimidazoles compared with those of topoisomerases of mammalian (calf thymus)
      origin. The most active inhibitors of the parasite enzymes were also highly
      effective in an in vivo animal model of P. carinii pneumonia. Selected dicationic
      substituted bis-benzimidazoles also strongly inhibited the induction of the
      topoisomerase I- and II-mediated cleavable complex, suggesting that the
      biologically active DNA minor groove-binding molecules inhibit the enzyme-DNA
      binding step of the topoisomerase reaction sequence. The apparent selectivities
      for the parasite enzymes and the low levels of toxicity to mammalian cells for
      the biologically active bis-benzimidazoles suggest that these compounds hold
      promise as effective therapeutic agents in the treatment of a life-threatening
      AIDS-related disease, P. carinii pneumonia.

PMID- 7810996
TI  - Contribution of VanY D,D-carboxypeptidase to glycopeptide resistance in
      Enterococcus faecalis by hydrolysis of peptidoglycan precursors.
AB  - The vanR, vanS, vanH, vanA, and vanX genes of enterococcal transposon Tn1546 were
      introduced into the chromosome of Enterococcus faecalis JH2-2. Complementation of
      this portion of the van gene cluster by a plasmid encoding VanY D,D
      carboxypeptidase led to a fourfold increase in the vancomycin MIC (from 16 to 64
      micrograms/ml). Multicopy plasmids pAT80 (vanR vanS vanH vanA vanX) and pAT382
      (vanR vanS vanH vanA vanX vanY) conferred similar levels of vancomycin resistance
      to JH2-2. The addition of D-alanine (100 mM) to the culture medium restored the
      vancomycin susceptibility of E. faecalis JH2-2/pAT80. The pentapeptide UDP-MurNAc
      L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala partially replaced pentadepsipeptide UDP
      MurNAc-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Lac when the strain was grown in the
      presence of D-alanine. In contrast, resistance mediated by pAT382 was almost
      unaffected by the addition of the amino acid. Expression of the vanY gene of
      pAT382 resulted in the formation of the tetrapeptide UDP-MurNAc-L-Ala-gamma-D-Glu
      L-Lys-D-Ala, indicating that a portion of the cytoplasmic precursors had been
      hydrolyzed. These results show that VanY contributes to glycopeptide resistance
      in conditions in which pentapeptide is present in the cytoplasm above a threshold
      concentration. However, the contribution of the enzyme to high-level resistance
      mediated by Tn1546 appears to be moderate, probably because hydrolysis of D
      alanyl-D-alanine by VanX efficiently prevents synthesis of the pentapeptide.

PMID- 7810997
TI  - Inhibition of sterol biosynthesis in Saccharomyces cerevisiae and Candida
      albicans by 22,23-epoxy-2-aza-2,3-dihydrosqualene and the corresponding N-oxide.
AB  - The abilities of 22,23-epoxy-2-aza-2,3-dihydrosqualene and the corresponding N
      oxide, 22,23-epoxy-2-aza-2,3-dihydrosqualene-N-oxide, to inhibit sterol
      biosynthesis were studied in microsomes and cells of Saccharomyces cerevisiae and
      Candida albicans. 22,23-Epoxy-2-aza-2,3-dihydrosqualene, which differs from the
      other inhibitor only in lacking oxygen at position 2, exhibited higher inhibitory
      properties in all preparations tested. The different levels of effectiveness of
      the two azasqualene derivatives were evident mostly in microsomes from S.
      cerevisiae (the 50 inhibitory concentrations of the 2-aza derivative and the
      corresponding N-oxide on oxidosqualene cyclase were 30 and 120 microM
      respectively) and in cell cultures of the same strain (1 order of magnitude
      separated the inhibitory activities of the two compounds on sterol biosynthesis).
      A possible explanation for the differences between 22,23-epoxy-2-aza-2,3
      dihydrosqualene and the corresponding N-oxide arose from the study of their
      metabolic fates in vivo and in vitro. While the 2-aza derivative did not undergo
      any transformation, the N-oxide compound was actively reduced to the
      corresponding amine in microsomes and in cells of both yeast strains. 22,23-Epoxy
      2-aza-2,3-dihydrosqualene-N-oxide seems to behave as a proinhibitor of sterol
      biosynthesis, becoming active only after transformation into the active form
      22,23-epoxy-2-aza-2,3-dihydrosqualene.

PMID- 7810999
TI  - Pharmacokinetics of spiramycin in the rhesus monkey: transplacental passage and
      distribution in tissue in the fetus.
AB  - Transplacental transfer of spiramycin was investigated in a rhesus monkey model
      to study whether the antibiotic reaches therapeutic levels in the fetus.
      Spiramycin concentrations were measured by bioassay and high-performance liquid
      chromatography. Pharmacokinetic parameters were determined for bioactive
      spiramycin as measured by the bioassay. Pharmacokinetic pilot studies showed that
      spiramycin distribution follows a two-compartment model in rhesus monkeys.
      Following a single intravenous dose of 50 or 250 mg, dose-dependent kinetics were
      observed. At a dose of 50 mg, 10% of the dose was excreted unchanged in the
      urine. At the higher dose of 250 mg, an oliguric effect was observed. Spiramycin
      concentrations in fetal serum were measured over time while the maternal
      concentration was maintained at a constant level. During a 5-h experiment, a
      maximum fetal-maternal serum ratio of 0.27 was found. In three fetuses,
      concentrations in serum and tissue were measured following intravenous
      administration of 50 mg of spiramycin twice daily to the mother for at least 7
      days. The fetal-maternal serum ratios were found to be 0.4 to 0.58 after
      intravenous administration of the final dose of 50 mg to the mother. It appeared
      that spiramycin accumulated in the soft tissues, especially in the liver and
      spleen, of both the mother and the fetus. The concentration in placental tissue
      appeared to be 10 to 20 times that of the concentration in fetal serum. The
      concentration of spiramycin in amniotic fluid was about five times higher than
      the concentration in fetal serum. Another important observation was that
      absolutely no spiramycin was found in the brain.

PMID- 7810998
TI  - Intracellular activity of azithromycin against bacterial enteric pathogens.
AB  - Azithromycin, a new azalide antibiotic, is active in vitro against a variety of
      enteric bacterial pathogens. Since it is concentrated inside human neutrophils
      and other cells, it might be particularly useful in the treatment of infections
      caused by enteropathogens that invade host tissues. The intracellular activity of
      azithromycin against several enteric pathogens that had been phagocytosed by
      neutrophils was determined. Azithromycin was effective in reducing the
      intracellular viabilities of almost all strains tested, including representative
      strains of Salmonella, Shigella, and enteroinvasive, enteropathogenic,
      enterotoxigenic, and enterohemorrhagic Escherichia coli. Erythromycin was also
      effective in this model system, although azithromycin was generally more
      effective than erythromycin against strains of invasive enteric pathogens.
      Cefotaxime reduced intracellular bacterial viability to a lesser extent than
      either azithromycin or erythromycin. The presence of neutrophils did not
      significantly affect the activity of azithromycin in this system. Azithromycin
      may be a useful agent for the treatment of bacterial diarrhea, and clinical
      trials should be considered.

PMID- 7811000
TI  - Effectiveness of spiramycin for treatment of congenital Toxoplasma gondii
      infection in rhesus monkeys.
AB  - The effectiveness of spiramycin for the treatment of rhesus monkey fetuses
      congenitally infected with Toxoplasma gondii was studied. Eight monkeys were
      infected at day 90 of pregnancy. This is comparable to the second trimester of
      organogenetic development in humans. Transmission of infection was found
      prenatally in five of the eight monkeys by detection of the parasite in the
      amniotic fluid. Treatment with spiramycin (20 mg/kg/day in two intermittent doses
      given intravenously) was started as soon as fetal infection was proven and was
      continued until birth. Nine to 14 days after initiation of treatment, the
      parasite was still detectable in amniotic fluid samples from four of these five
      cases. However, the parasite was detected only by PCR and not by mouse
      inoculation. T. gondii was also detected only by PCR in the placenta of one
      monkey that delivered prematurely. This monkey received spiramycin treatment for
      only 2 weeks. In the four monkeys that received treatment for about 7 weeks, the
      parasite was not present at birth in the placenta nor in amniotic fluid or
      neonatal organs. Spiramycin accumulates mainly in maternal tissues. Although
      concentrations in neonatal tissue were found to be 5 to 28 times higher than the
      corresponding concentrations in neonatal serum, the concentrations in neonatal
      tissue were still 11 to 16 times lower than those found in the mothers. However,
      no spiramycin was found in the fetal brains. Early treatment with spiramycin may
      prevent transmission of infection to the fetus but most probably cannot interrupt
      an existing brain infection, which is the most severe outcome of congenital
      toxoplasmosis in humans.

PMID- 7811001
TI  - Characteristics of murine model of genital infection with Chlamydia trachomatis
      and effects of therapy with tetracyclines, amoxicillin-clavulanic acid, or
      azithromycin.
AB  - Following intravaginal inoculation of progesterone-treated outbred mice with
      Chlamydia trachomatis MoPn, 4 to 6 log10 inclusion-forming units were recovered
      in vaginal swabs for 21 days but all animals were culture negative after 28 days.
      Serum antibody titers were elevated and remained high for at least 70 days.
      Between 28 and 70 days, upper tract infection (inflammation and distension of the
      uterine horns, occlusion of oviducts with inflammatory exudate, pyosalpinx, and
      hydrosalpinx) was seen in > 80% of the animals. Mice were dosed orally,
      commencing at 7 days after infection, with minocycline, doxycycline, or
      amoxicillin-clavulanate. Further groups received azithromycin either as a single
      high dose or as lower once-daily doses. In addition, minocycline and amoxicillin
      clavulanate were administered at 24 h after infection, and this early treatment
      prevented elevation of antibody titers whereas delayed therapy did not. Vaginal
      swabs from mice in all treatment regimens were culture negative except for 25% of
      mice receiving either early amoxicillin-clavulanate or low-dose azithromycin,
      which yielded low numbers (20 to 70 inclusion-forming units) of chlamydiae.
      Numbers of fertile mice in the early treatment regimens and their litter sizes
      were similar to those of noninfected controls, although 25% of amoxicillin
      clavulanate-treated mice had unilateral hydrosalpinges. In comparison, 88% of
      untreated mice developed hydrosalpinges and only 25% conceived. Delayed dosing
      did not affect the outcome of amoxicillin-clavulanate therapy but did diminish
      the protective efficacy of minocycline such that 50% of treated mice had either
      unilateral hydrosalpinges or ovarian abscesses. Doxycycline and azithromycin were
      highly effective in restoring fertility. This model makes possible the study of
      both short- and long-term outcomes of chlamydial infection.

PMID- 7811002
TI  - Cloning and nucleotide sequence of Pseudomonas aeruginosa DNA gyrase gyrA gene
      from strain PAO1 and quinolone-resistant clinical isolates.
AB  - The Pseudomonas aeruginosa DNA gyrase gyrA gene was cloned and sequenced from
      strain PAO1. An open reading frame of 2,769 bp was found; it coded for a protein
      of 923 amino acids with an estimated molecular mass of 103 kDa. The derived amino
      acid sequence shared 67% identity with Escherichia coli GyrA and 54% identity
      with Bacillus subtilis GyrA, although conserved regions were present throughout
      the sequences, particularly toward the N terminus. Complementation of an E. coli
      mutant with a temperature-sensitive gyrA gene with the PAO1 gyrA gene showed that
      the gene is expressed in E. coli and is able to functionally complement the E.
      coli DNA gyrase B subunit. Expression of PAO1 gyrA in E. coli or P. aeruginosa
      with mutationally altered gyrA genes caused a reversion to wild-type quinolone
      susceptibility, indicating that the intrinsic susceptibility of the PAO1 GyrA to
      quinolones is comparable to that of the E. coli enzyme. PCR was used to amplify
      360 bp of P. aeruginosa gyrA encompassing the so-called quinolone resistance
      determining region from ciprofloxacin-resistant clinical isolates from patients
      with cystic fibrosis. Mutations were found in three of nine isolates tested;
      these mutations caused the following alterations in the sequence of GyrA: Asp at
      position 87 (Asp-87) to Asn, Asp-87 to Tyr, and Thr-83 to Ile. The resistance
      mechanisms in the other six isolates are unknown. The results of the study
      suggested that mechanisms other than a mutational alteration in gyrA are the most
      common mechanism of ciprofloxacin resistance in P. aeruginosa from the lungs of
      patients with cystic fibrosis.

PMID- 7811004
TI  - Mechanism of inhibition of DNA gyrase by cyclothialidine, a novel DNA gyrase
      inhibitor.
AB  - We investigated how cyclothialidine (Ro 09-1437), a novel DNA gyrase inhibitor
      belonging to a new chemical class of compounds, acts to inhibit Escherichia coli
      DNA gyrase. Cyclothialidine up to 100 micrograms/ml showed no effect on DNA
      gyrase when linear DNA was used as a substrate. Under the same conditions,
      quinolones, which inhibit the resealing reaction of DNA gyrase, caused a decrease
      in the amount of linear DNA used. No effect of cyclothialidine was observed on
      the accumulation of the covalent complex of DNA and the A subunit of DNA gyrase
      induced by ofloxacin in the absence of ATP. The effect of cyclothialidine on the
      DNA supercoiling reaction was antagonized by ATP, reducing the inhibitory
      activity 11-fold as the ATP concentration was increased from 0.5 to 5 mM.
      Cyclothialidine competitively inhibited the ATPase activity of DNA gyrase (Ki = 6
      nM). The binding of [14C]benzoyl-cyclothialidine to E. coli gyrase was inhibited
      by ATP and novobiocin, but not by ofloxacin. These results suggest that
      cyclothialidine acts by interfering with the ATPase activity of the B subunit of
      DNA gyrase. Cyclothialidine was active against a DNA gyrase resistant to
      novobiocin, suggesting that its precise site of action might be different from
      that of novobiocin.

PMID- 7811003
TI  - In vivo efficacy of a broad-spectrum cephalosporin, ceftriaxone, against
      penicillin-susceptible and -resistant strains of Streptococcus pneumoniae in a
      mouse pneumonia model.
AB  - The increasing emergence of penicillin-resistant (Pr) strains of Streptococcus
      pneumoniae could pose a therapeutic problem in the next few years. Ceftriaxone
      (CRO), a broad-spectrum cephalosporin, exhibits a smaller increase in MICs
      against Pr S. pneumoniae strains than amoxicillin (AMO) (usually referred as to
      the "gold standard" therapy for pneumococcal infections). Therefore, we compared
      their respective efficacies in a leukopenic Swiss mouse model of pneumococcal
      pneumonia. Infection was induced with two serotype 19 strains: a penicillin
      susceptible (Ps) strain (MICs of < 0.01 for penicillin, 0.03 for AMO, and 0.03
      for CRO) and a Pr strain (MICs of 4 for penicillin, 2 for AMO, and 0.5 for CRO).
      Untreated mice died within 2 or 3 days. Against the Ps strain, the minimal
      protective dose (two subcutaneous injections at 12-h intervals for 3 days) for
      both CRO and AMO was 5 mg/kg of body weight (87% survivors). Ten-fold-increased
      doses of CRO (50 mg/kg) gave similar protection (75% survivors) against the Pr
      strain, whereas 20- and 40-fold-increased doses of AMO protected 0 and 34% of the
      animals, respectively, against the Ps strain. CRO had a marked and prolonged
      antibacterial effect in the lungs (2.7-log-unit reduction of CFU in 24 h after a
      single 50-mg/kg injection) against the Pr strain in comparison with AMO. A
      standard dosage of 50 mg of CRO per kg in mice resulted in peak levels in serum
      and protein binding comparable to those observed with 1 g given intravenously in
      humans. This dosage remained effective against a highly Pr S. pneumoniae strain
      in this model. The microbiological activity and pharmacodynamic and
      pharmacokinetic properties of CRO (time during which concentrations exceed the
      MIC for the test pathogen [delta t MIC], > or less than 8 h; and peak/MIC ratio,
      >90 for free active drug) accounted for its efficacy relative to AMO (50 mg/kg:
      delta t MIC, <2; peak/MIC ratio, <25) against the highly Pr S. pneumoniae strain
      used in this study.

PMID- 7811005
TI  - In vitro antibacterial activity and beta-lactamase stability of SY5555, a new
      oral penem antibiotic.
AB  - The antibacterial activity of SY5555, a new oral penem antibiotic, was compared
      with those of cefaclor, cefixime, and cefteram. SY5555 was more active than the
      comparison agents against methicillin-susceptible Staphylococcus aureus,
      Staphylococcus epidermidis, Streptococcus pneumoniae, Enterococcus faecalis,
      Citrobacter freundii, Enterobacter cloacae, Morganella morganii, Acinetobacter
      calcoaceticus, Clostridium spp., and Bacteroides fragilis. Against Providencia
      spp., Proteus spp., and Haemophilus influenzae, SY5555 was less active than
      cefixime or cefteram. SY5555 was inactive against methicillin-resistant S.
      aureus. Enterococcus faecium, Serratia marcescens, Pseudomonas aeruginosa, and
      Xanthomonas maltophilia, as were the comparison agents. The bactericidal
      activities of SY5555, cefixime, and cefteram were at or slightly greater than the
      MICs for clinical isolates of Escherichia coli and Klebsiella pneumoniae. SY5555
      was not hydrolyzed by various types of beta-lactamases. However, SY5555 and the
      comparison agents were hydrolyzed by X. maltophilia (L-1) and P.
      aeruginosa/pMS354 beta-lactamases, two Bush group 3 beta-lactamases, SY5555
      showed a high affinity, as did cefixime and cefteram, for cephalosporinases from
      C. freundii GN7391 and E. cloacae GN7471 strains. These results suggest that
      SY5555 may be more specific than existing beta-lactam antibiotics.

PMID- 7811006
TI  - Overproduction of a low-affinity penicillin-binding protein and high-level
      ampicillin resistance in Enterococcus faecium.
AB  - Five ampicillin-resistant clinical isolates of Enterococcus faecium were analyzed
      for a correlation between overproduction of the low-affinity penicillin-binding
      protein (PBP 5) and the level of ampicillin resistance. Comparison was made with
      one susceptible clinical isolate and its ampicillin-resistant derivative obtained
      in the laboratory by selection with increasing concentrations of penicillin.
      Overproduction of the low-affinity PBP relative to the susceptible isolate was
      noted in moderately resistant strains (MIC, 32 micrograms/ml) but not in highly
      resistant strains (MIC, 128 micrograms/ml). Polyclonal antibodies specifically
      reacting with the low-affinity PBP of Enterococcus hirae, Enterococcus faecalis,
      and Enterococcus faecium (M. Ligozzi, M. Aldegheri, S. C. Predari, and R.
      Fontana, FEMS Microbiol. Lett. 83:335-340, 1991) were used to determine the
      amount of this PBP in the E. faecium isolates. In all strains, the antibody
      preparation reacted with a membrane protein of the same molecular mass as PBP 5.
      The amount of this protein was very small in the susceptible strain but large in
      all of the resistant strains. These results suggest that the highly resistant
      strains also overproduced the low-affinity PBP, which, compared with PBP 5 of
      moderately resistant strains, appeared to be modified in its penicillin-binding
      capability.

PMID- 7811008
TI  - Characterization of mutations in Mycobacterium smegmatis involved in resistance
      to fluoroquinolones.
AB  - Fluoroquinolone-resistant mutants of Mycobacterium smegmatis have been obtained
      in vitro by using ofloxacin as a selecting agent. Two types of mutants were
      identified according to their quinolone resistance patterns. Type 1 showed a low
      level of resistance to ofloxacin (MIC of 8 micrograms/ml), whereas a high level
      of resistance to this drug (MICs of 32 to 64 micrograms/ml) characterized type 2.
      By using two oligonucleotide primers homologous to DNA sequences flanking the
      quinolone resistance-determining region (QRDR) in the gyrA gene of Escherichia
      coli and Staphylococcus aureus, a 150-bp DNA fragment was obtained by PCR
      amplification from total DNA of two wild-type and five mutant strains of M.
      smegmatis. The nucleotide sequences of the amplified fragments were determined.
      The deduced amino acid sequence from the wild-type strains showed ca. 79%
      similarity with the QRDR in the gyrase A subunit from other gram-positive and
      gram-negative bacteria. The DNA sequences obtained from the fluoroquinolone
      resistant mutants of M. smegmatis exhibited nucleotide modifications compared
      with the wild-type QRDR. The QRDR from type 1 mutants had a C-T or an A-G
      transition leading to a change from Ala-83 to Val or Asp-87 to Gly, respectively.
      The QRDR from type 2 mutants had a Val-83 mutation or both Val-83 and Gly-87
      mutations detected in the type 1 mutants. These results suggest that point
      mutations in the QRDR of the mycobacterial gyrA gene are responsible for acquired
      quinolone resistance in M. smegmatis.

PMID- 7811007
TI  - Stimulation of genetic instability and associated large genomic rearrangements in
      Streptomyces ambofaciens by three fluoroquinolones.
AB  - In Streptomyces ambofaciens NSA2002, pigmented wild-type colonies spontaneously
      give rise to pigment-negative (Pig-) mutants at a frequency of about 0.5%. This
      genetic instability is related to large deletions which can be associated with
      amplifications of DNA sequences. The influence of three fluoroquinolones
      (ciprofloxacin, enoxacin, and norfloxacin) on this property was investigated. At
      a survival rate higher than 60%, most colonies showed a patchwork phenotype
      consisting of phenotypically heterogeneous colonies harboring numerous mutant
      sectors. Moreover, the frequency of Pig- mutants rose to more than 90% at
      survival rates equal to or higher than 10%. Induced Pig- mutants showed the same
      phenotypical features as did spontaneous mutants. Most of them also harbored
      deletions, associated in some cases with DNA amplifications, in two loci of the
      large unstable region, AUD6 and AUD90 (derived from amplifiable unit of DNA). The
      size of deletions in induced mutants could rise to 1.5 Mb. These results show
      that ciprofloxacin, enoxacin, and norfloxacin greatly stimulate genetic
      instability and the occurrence of DNA rearrangements in S. ambofaciens. Moreover,
      these three fluoroquinolones had the same rank order for both toxic (i.e.,
      antibacterial) and genotoxic activities. If the antibacterial effect of
      fluoroquinolones in S. ambofaciens is due to their interference with DNA gyrase,
      as shown for some other organisms, the genotoxic effect observed could be due to
      their interaction with this type II topoisomerase. This suggests that DNA gyrase
      is involved in the process of genetic instability in S. ambofaciens.

PMID- 7811009
TI  - Effect of fialuridine on replication of mitochondrial DNA in CEM cells and in
      human hepatoblastoma cells in culture.
AB  - Fialuridine (FIAU) is a nucleoside analog with potent activity against hepatitis
      B virus in vitro and in vivo. In this report, the effect of FIAU on mitochondrial
      DNA (mtDNA) replication in vitro was investigated. CEM cells, a cell line derived
      from human T cells, were incubated for 6 days in up to 20 microM FIAU. Total
      cellular DNA was isolated, normalized for the number of cells, and slot
      hybridized to a probe specific for mtDNA sequences. Treatment of CEM cells with
      FIAU did not result in a dose-dependent decrease in the amount of mtDNA. In
      contrast, dideoxycytidine (ddC) inhibited mtDNA replication by 50% at a
      concentration of approximately 0.1 microM. After 6 days of incubation, both
      compounds displayed a 50% toxic dose at a concentration of approximately 2 microM
      in CEM cells and approximately 34 microM in human hepatoblastoma cells (HepG2).
      In further experiments, CEM cells were incubated for 15 days in up to 2.5 microM
      FIAU, and again, no inhibition of mtDNA was observed. Over a 6-day incubation,
      FIAU, at concentrations of up to 200 microM, also failed to inhibit mtDNA
      replication in either HepG2 or HepG2 cells which constitutively replicate duck
      hepatitis B virus. In contrast, ddC inhibited mtDNA replication in these cells
      with a 50% inhibitory concentration of approximately 0.2 microM over a 6-day
      incubation. Treatment of cells with either FIAU or ddC resulted in a dose
      dependent increase in lactate levels in the cell medium, indicating that any
      effect of FIAU on mitochondrial function may not be related to inhibition of
      mtDNA replication on the basis of the in vitro data. Alternative explanations for
      mitochondrial toxicity are considered.

PMID- 7811010
TI  - Evaluation of antimicrobial activities of clarithromycin and 14
      hydroxyclarithromycin against three strains of Haemophilus influenzae by using an
      in vitro pharmacodynamic model.
AB  - An in vitro pharmacodynamic model was used to simulate the in vivo
      pharmacokinetics of clarithromycin and 14-hydroxyclarithromycin in order to
      generate time-kill curves for three clinical isolates of Haemophilus influenzae
      (isolates 2019, 91-183, and 1746). Representative concentrations in serum or lung
      tissue and the pharmacokinetic parameters of clarithromycin and the 14-hydroxy
      metabolite, separately and in combination, were simulated for the time-kill
      studies. Amoxicillin-clavulanic acid was used as a control drug. The simulation
      of typical concentrations of the macrolides in serum in time-kill studies
      resulted in magnitudes of bacterial killing that were less than (for strains 2019
      and 91-183, MICs = 4 mg/liter for clarithromycin and 14-hydroxy-clarithromycin)
      or equal to (for strain 1746, MIC = 1 mg/liter for clarithromycin and 14
      hydroxyclarithromycin) those observed in amoxicillin-clavulanic acid studies.
      When typical concentrations in lung tissue were simulated, total log decreases in
      bacterial counts were greater than those achieved with typical concentrations in
      serum and, in the case of strain 1746, exceeded the magnitude observed with the
      control drug. In each case, the time to 3-log-unit killing was longer for the
      macrolides than for amoxicillin-clavulanic acid. Time-kill curve analyses
      demonstrated the presence of synergy (defined as a 2-log-unit decrease in the CFU
      per milliliter between the combination and the most active constituent at any
      time point) for the combination of clarithromycin and 14-hydroxyclarithromycin at
      simulated concentrations in serum for one strain of H. influenzae (isolate 91
      183). Synergism is likely bacterial strain specific, and the presence of synergy
      may be dependent on the antibiotic concentrations that are tested. Evaluation of
      the kill curve kinetics in terms of bactericidal rate for the various starting
      concentrations of clarithromycin did not result in a clear demonstration of
      either concentration-dependent or concentration-independent bactericidal
      activity.

PMID- 7811011
TI  - Assays to detect and characterize human immunodeficiency virus type 1 (HIV-1)
      receptor antagonists, compounds that inhibit binding of the HIV-1 surface
      glycoprotein, gp120, to the CD4 receptor on human T lymphocytes.
AB  - Human immunodeficiency virus type 1 infects human helper T lymphocytes by an
      interaction between gp120, the viral coat protein, and the T-cell receptor CD4.
      Two microtiter-based immunoassays, an enzyme-linked immunosorbent assay (ELISA)
      and a particle concentration fluorescence assay, were developed to measure gp120
      CD4 binding and were then used to screen a variety of compounds for the
      inhibition of this interaction. Additional protocols, called "consumption
      assays," were defined to distinguish inhibitors which functioned by sequestering
      either gp120 or CD4 to prevent the final effective bimolecular interaction.
      Monoclonal antibodies of defined specificity and compounds known from other
      published studies to inhibit gp120-CD4 binding were tested in an attempt to
      validate the assays used in the study. Once the capacity of these assays to
      detect known gp120-CD4 inhibitors was confirmed, they were used to screen
      synthetic agents and fermentation broths for novel compounds that might be used
      as human immunodeficiency virus receptor antagonists. A 2,4-diaminoquinazoline,
      CP-101,816-1, was found to inhibit this interaction (50% inhibitory concentration
      in ELISA, 32.5 micrograms/ml) and to interact more strongly with CD4 than with
      gp120 in the consumption assays. The identification of a novel inhibitor, a 2,4
      diaminoquinazoline, confirmed that such assays are useful for the detection of
      human immunodeficiency virus type 1 receptor antagonists.

PMID- 7811012
TI  - Quinolone resistance mutations in the DNA gyrase gyrA and gyrB genes of
      Staphylococcus aureus.
AB  - A 6.4-kb DNA fragment containing the DNA gyrase gyrA and gyrB genes was cloned
      and sequenced from the quinolone-susceptible Staphylococcus aureus type strain
      ATCC 12600. An expression plasmid was constructed by inserting the cloned genes
      into the Escherichia coli-S. aureus shuttle vector pAT19, and deletion plasmids
      carrying only functional gyrA and gyrB genes were derived from this plasmid. An
      efficient transformation system for S. aureus RN4220 was established by using
      these plasmids. Quinolone-resistant mutants of S. aureus RN4220 were isolated by
      three-step selection with quinolones. The first- and second-step mutants were
      considered to be transport mutants, and the third-step mutants were divided into
      five groups with respect to their resistance patterns and transformation results
      with gyrA and gyrB genes. Sequencing analysis of the resulting mutant gyrase
      genes showed that they had the following point mutations: group 1, Ser-84 (TCA)
      to Leu (TTA) in GyrA; group 2, Ser-84 (TCA) to Ala (GCA), Ser-85 (TCT) to Pro
      (CCT), or Glu-88 (GAA) to Lys (AAA) in GyrA; group 3, Asp-437 (GAC) to Asn (AAC)
      in GyrB; group 4, Arg-458 (CGA) to Gln (CAA) in GyrB; and group 5, Ser-85 (TCT)
      to Pro (CCT) in GyrA and Asp-437 (GAC) to Asn (AAC) in GyrB. When the gyrA and/or
      gyrB mutants were transformed with the wild-type gyrA and/or gyrB plasmids, they
      became quinolone susceptible, but transformants with the plasmids having the same
      mutations on the gyrA and/or gyrB genes did not confer susceptibility. These
      results indicate that mutations in both gyrA and gyrB can be responsible for
      quinolone resistance in S. aureus.

PMID- 7811013
TI  - Ticarcillin-clavulanic acid pharmacokinetics in preterm neonates with presumed
      sepsis.
AB  - The objective of the reported study was to characterize the pharmacokinetics of
      ticarcillin and clavulanic acid in premature low-birth-weight (less than 2,200 g)
      neonates with presumed sepsis. Eleven infants received 12 courses of ticarcillin
      clavulanic acid at 75 mg/kg of body weight intravenously every 12 h. Blood
      samples were collected at 0.5, 1.5, 4, and 8 h following the infusion of the
      initial dose. The concentrations of ticarcillin and clavulanic acid were
      determined by a microbiologic assay. Median (interpatient coefficients of
      variation) values for the volume of the central compartment, total steady-state
      volume, distributional clearance, total clearance, and terminal elimination half
      life for ticarcillin were 0.030 liter/kg (21%), 0.26 liter/kg (48%), 0.41
      liter/h/kg (47%), 0.047 liter/h/kg (47%), and 4.2 h (45%), respectively. For
      clavulanic acid the parameters were 0.28 liter/kg (32%), 0.36 liter/kg (34%), 11
      liters/h/kg (36%), 0.12 liters/h/kg (72%), and 1.95 h (40%), respectively. Our
      results suggest that the current dosing recommendations of 75 mg/kg every 12 h
      risk subtherapeutic clavulanic acid concentrations and that 50 mg/kg every 6 h is
      a more rational dosing strategy.

PMID- 7811014
TI  - Sterol composition of Cryptococcus neoformans in the presence and absence of
      fluconazole.
AB  - Analysis of the sterol compositions of 13 clinical isolates of the pathogenic
      yeast Cryptococcus neoformans obtained from five patients with recurring
      cryptococcal meningitis showed that, unlike Candida albicans, the major sterols
      synthesized by this yeast were obtusifoliol (range, 21.1 to 68.2%) and ergosterol
      (range, 0.0 to 46.5%). There was considerable variation in the sterol contents
      among the 13 isolates, with total sterol contents ranging from 0.31 to 5.9% of
      dry weight. The isolates from the five patients who had relapses had different
      total sterol contents and compositions in comparison with those of the
      pretreatment isolates, indicating either that the sterols had been changed by
      therapy or that the patients were infected with new isolates with different
      sterol compositions. Growth of the cryptococcal isolates in the presence of
      subinhibitory concentrations of fluconazole (0.25x the MIC) significantly altered
      the sterol content and pattern. The total sterol content decreased in nine
      isolates and increased in four isolates in response to pretreatment with
      fluconazole. Fluconazole had no consistent effect on ergosterol levels. In
      contrast, fluconazole caused a decrease in obtusifoliol levels and an increase in
      4,14-dimethylzymosterol levels in all isolates. These results indicate extensive
      diversity in sterol content, sterol composition, and sterol synthesis in response
      to subinhibitory concentrations of fluconazole in C. neoformans strains. We
      propose that fluconazole inhibits the sterol synthesis of C. neoformans by
      interfering with both 14 alpha-demethylase-dependent and -independent pathways.
      No correlation between the sterol compositions of C. neoformans isolates and
      their susceptibilities to fluconazole was found.

PMID- 7811015
TI  - Bactericidal activities of teicoplanin, vancomycin, and gentamicin alone and in
      combination against Staphylococcus aureus in an in vitro pharmacodynamic model of
      endocarditis.
AB  - We adapted an in vitro pharmacodynamic model of infection to incorporate
      simulated endocardial vegetations. The bactericidal activities of teicoplanin,
      vancomycin, gentamicin, and various combinations of these drugs were studied
      against a strain of methicillin-susceptible Staphylococcus aureus obtained from a
      patient being treated for endocarditis at Detroit Receiving Hospital. Bacteria
      were grown overnight, concentrated, and added to a mixture of cryoprecipitate
      (80%) and thrombin (10%) to achieve approximately 5 x 10(9) CFU/g. Fibrin clots
      (8 to 10) were suspended into the model, removed at 24, 48, and 72 h in
      duplicate, weighed, and homogenized in 1.25% trypsin. Control experiments were
      conducted to characterize the growth kinetics. The following antibiotics were
      administered to simulate the pharmacokinetics of the drugs in humans: teicoplanin
      at 3 and 15 mg/kg of body weight, vancomycin at 15 mg/kg, and gentamicin at 1
      mg/kg. Fibrin clot samples used to detect resistance were plated on antibiotic
      containing tryptic soy agar plates. For the teicoplanin and vancomycin regimens,
      protein binding to cryoprecipitate, thrombin, and fibrin clot was determined to
      be 32, 43, and 50% and 26, 28, and 29%, respectively. In comparison with no
      treatment, vancomycin or teicoplanin at 15 mg/kg or either of these regimens
      combined with gentamicin significantly reduced bacterial counts (P < 0.0001).
      Monotherapy with teicoplanin at 3 mg/kg or gentamicin resulted in no killing
      activity. Combination treatment with teicoplanin at 3 mg/kg and gentamicin
      resulted in the killing of approximately 2 log10 CFU/g by 72 h and the
      development of resistance to gentamicin. The results obtained with the in vitro
      model of endocarditis are similar to the results reported by several
      investigators with the rabbit model of infective endocarditis. This unique
      infection model is useful for designing initial drug dosage regimens and may be
      predictive of drug efficacy against infective endocarditis.

PMID- 7811016
TI  - Effects of teicoplanin and those of vancomycin in initial empirical antibiotic
      regimen for febrile, neutropenic patients with hematologic malignancies. Gimema
      Infection Program.
AB  - The efficacy and toxicity of teicoplanin and vancomycin in the initial empirical
      antibiotic regimen in febrile, neutropenic patients with hematologic malignancies
      were compared in a prospective, randomized, unblinded, multicenter trial in the
      setting of 29 hematologic units in tertiary-care or university hospitals. A total
      of 635 consecutive febrile patients with hematologic malignancies and
      chemotherapy-induced neutropenia were randomly assigned to receive intravenously
      amikacin plus ceftazidime plus either teicoplanin at 6 mg/kg of body weight once
      daily or vancomycin at 1 g twice daily. An efficacy analysis was done for 527
      evaluable patients: 275 treated with teicoplanin and 252 treated with vancomycin.
      Overall, successful outcomes were recorded for 78% of patients who received
      teicoplanin and 75% of those who were randomized to vancomycin (difference, 3%;
      95% confidence interval [CI], -10 to 4%; P = 0.33). A total of 102 patients
      presented with primary, single-agent, gram-positive bacteremia. Coagulase
      negative staphylococci accounted for 42%, Staphylococcus aureus accounted for
      27%, and streptococci accounted for 21% of all gram-positive blood isolates. The
      overall responses to therapy of gram-positive bacteremias were 92 and 87% for
      teicoplanin and vancomycin, respectively (difference, 5%; CI, -17 to 6%; P =
      0.22). Side effects, mainly represented by skin rash, occurred in 3.2 and 8% of
      teicoplanin- and vancomycin-treated patients, respectively (difference, -4.8%;
      CI, 0.7 to 8%; P = 0.03); the rate of nephrotoxicity was 1.4 and 0.8% for the
      teicoplanin and vancomycin groups, respectively (difference, 0.6%; CI, -2 to 1%;
      P = 0.68). Further infections were caused by gram-positive organisms in two
      patients (0.7%) treated with teicoplanin and one patient (0.4%) who received
      vancomycin (difference, 0.3%; CI, -0.9 to 1.0%; P = 0.53). Overall mortalities
      were 8.5 and 11% for teicoplanin- and vancomycin-treated patients, respectively
      (difference, -2.5%; CI, - 2 to 7%; P = 0.43); death was caused by primary gram
      positive infections in three patients (1%) in each treatment group. When used for
      initial empirical antibiotic therapy in febrile, neutropenic patients,
      teicoplanin was at least as efficacious as vancomycin, but it was associated with
      fewer side effects.

PMID- 7811017
TI  - Effect of treatment with methicillin and gentamicin in a new experimental mouse
      model of foreign body infection.
AB  - A new mouse model of foreign body infection has been developed. Intraperitoneal
      placement of a silicone catheter followed by injection of 10(8) Staphylococcus
      aureus organisms resulted in a reproducible, localized foreign body infection.
      The infection persisted as an intra-abdominal abscess surrounding the catheter
      for at least 30 days. Treatment with up to nine doses of methicillin or
      gentamicin or both was started 3 days after infection. The treatment showed a
      significant effect (P < 0.05), measured as reduction of bacteria on the foreign
      body, for all three regimens with a reduction of up to 2 log units, but no
      synergism was observed. The result of the treatment was poor, despite the facts
      that the local concentrations of methicillin were greater than the MIC for at
      least 72 h and that nine peak concentrations of gentamicin of > 13 micrograms/ml
      were obtained. The poor result of the treatment was not caused by development of
      antibiotic resistance or influenced by protein concentration, pH, or local
      presence in the pus of inhibitors of antibiotics. Both antibiotics showed good
      effects in time-kill studies in vitro on bacteria on catheters taken out of
      infected mice and catheters infected in vitro. During treatment, the proportion
      of intracellular bacteria increased in all treated mice to 60 to 75% compared
      with 20 to 30% in nontreated mice (P < 0.05). This indicates that intracellular
      survival of staphylococci may influence the outcome of the treatment in foreign
      body infections.

PMID- 7811018
TI  - Metronidazole is bactericidal to dormant cells of Mycobacterium tuberculosis.
AB  - Very abrupt exposure to anaerobic conditions has a lethal effect on actively
      growing cultures of Mycobacterium tuberculosis. However, incubation under
      conditions in which oxygen is depleted gradually causes M. tuberculosis to shift
      down from active replication to dormancy. The dormant bacilli are resistant to
      the bactericidal effects of anaerobiosis and also exhibit partial or complete
      resistance to the bactericidal effects of isoniazid and rifampin. On the other
      hand, metronidazole, a drug specific for anaerobes, kills dormant tubercle
      bacilli under anaerobic conditions, but it has no effect on actively growing
      aerobic cultures. The lethal effect of metronidazole under anaerobic conditions
      is enhanced by rifampin. The possible implications of these findings on the
      phenomenon of latency in tuberculosis are discussed.

PMID- 7811019
TI  - Posttherapy suppression of genital herpes simplex virus (HSV) recurrences and
      enhancement of HSV-specific T-cell memory by imiquimod in guinea pigs.
AB  - Imiquimod, an immunomodulator with no direct in vitro antiviral activity, has in
      vivo anti-herpesvirus activity by inducing interferon and enhancing other only
      partially defined immune responses. Imiquimod treatment of primary genital herpes
      simplex virus (HSV) infection in guinea pigs reduces the level of genital disease
      by 90%. We further investigated its utility as suppressive therapy of recurrent
      disease in animals that had recently recovered from primary genital HSV-2
      disease. Imiquimod administered intravaginally once per day for 5 days reduced
      the number of recurrences only during treatment, while a 21-day regimen reduced
      the number of recurrences for 8 weeks. For the entire 10 weeks of observation,
      overall numbers of recurrences were reduced 67% by the 21-day imiquimod treatment
      (P < 0.0001). Latent HSV in ganglia was not affected by either regimen. Increased
      circulating alpha interferon activity was observed during therapy with both
      regimens. Interferon levels rapidly returned to baseline with cessation of
      treatment. Posttreatment, 5-day imiquimod treatment did not provide clinical
      benefit or enhancement of cell-mediated or cytokine responses. Twenty-one-day
      imiquimod treatment reduced both the number of clinical recurrences and levels of
      HSV antibody for 5 to 6 weeks posttreatment compared with the placebo.
      Additionally, 21-day imiquimod treatment enhanced HSV antigen-specific
      interleukin 2 production and proliferative responses by mononuclear cells (P <
      0.001) for 4 weeks after treatment. Twenty-one-day imiquimod therapy suppressed
      recurrent HSV genital disease during and for weeks after therapy, enhanced memory
      dependent cytokine and T-cell responses, and reduced the level of antibody
      responses.

PMID- 7811020
TI  - Study of comparative antipneumococcal activities of penicillin G, RP 59500,
      erythromycin, sparfloxacin, ciprofloxacin, and vancomycin by using time-kill
      methodology.
AB  - Time-kill studies were used to examine the in vitro activities of penicillin G,
      RP 59500, erythromycin, ciprofloxacin, sparfloxacin, and vancomycin against 10
      pneumococci expressing various degrees of susceptibility to penicillin and
      erythromycin. RP 59500 MICs for all strains were 0.5 to 2.0 micrograms/ml, while
      erythromycin MICs were 0.008 to 0.06 microgram/ml for erythromycin-susceptible
      strains and 32.0 to 64.0 micrograms/ml for erythromycin-resistant strains.
      Strains were more susceptible to sparfloxacin (0.125 to 0.5 microgram/ml) than to
      ciprofloxacin (0.5 to 4.0 micrograms/ml), and all were inhibited by vancomycin at
      MICs of 0.25 to 0.5 microgram/ml. Time-kill studies showed that antibiotic
      concentrations greater than the MIC were bactericidal for each strain, with the
      following exceptions. Erythromycin was bactericidal for one penicillin-resistant
      strain at 6 h, with regrowth after 12 and 24 h. Three penicillin-susceptible
      strains were bacteriostatically inhibited by erythromycin at concentrations
      greater than or equal to the MIC by 6 h. One penicillin-susceptible strain
      (penicillin MIC, 0.06 microgram/ml) was bacteriostatically inhibited by
      penicillin G at 24 h at the MIC or at one-half the MIC; a bactericidal effect was
      found only with penicillin G at concentrations of > or = 0.25 microgram/ml. At 10
      min after inoculation a 1- to 3-log10-unit reduction (90 to 99.9%) in the
      original inoculum was seen for 6 of 10 strains with RP 59500 at concentrations
      greater than or equal to the MIC. This effect was not found with any of the other
      compounds tested. A bactericidal effect was found at > or = 6 h with RP 59500 at
      concentrations of one-half to one-quarter the MIC in 7 of 10 strains, and a
      bacteriostatic effect was found in 3 or 10 strains, with regrowth at 24 h. One
      penicillin-resistant strain was examined by the time-kill methodology at 0, 1, 2,
      and 3 h. RP 59500 at a concentration equal to the MIC was bactericidal within 1
      h, and at a concentration of one-half the MIC it was bactericidal within 3 h.
      This phenomenon was not seen with the other antimicrobial agents tested. Regrowth
      of strains at ciprofloxacin concentrations equal to the MIC or at a one-half to
      one-quarter the MIC was found. For sparfloxacin, three of the four penicillin
      susceptible strains and two of four penicillin-resistant strains were
      bacteriostatically inhibited by 6 h. Bactericidal effects were found at 6, 12,
      and 24 h with both intermediate-resistant, one penicillin-susceptible, and two
      penicillin-resistant strains. Complete killing was observed with vancomycin at
      concentrations greater than MIC. Of the new compounds tested, RP 59500 and
      sparfloxacin show promise for the treatment of infections caused by penicillin
      susceptible and -resistant pneumococci. The clinical significance of rapid
      killing by RP 59500 remains to be determined.

PMID- 7811021
TI  - Comparison of aminoglycoside pharmacokinetics in Asian, Hispanic, and Caucasian
      patients by using population pharmacokinetic methods.
AB  - A population pharmacokinetic model for aminoglycosides was developed from 24
      Hispanic, 16 Asian, and 22 Caucasian patients. A nonparametric expectation
      maximization algorithm for population modeling was used. With this one
      compartment model, the parameters were the slope of the apparent volume of
      distribution versus weight (VS) and the slope of the elimination rate constant
      versus the creatinine clearance rate (KS). The mean VS (+/- standard deviation)
      was not different at 0.264 (+/- 0.05), 0.248 (+/- 0.055), and 0.260 (+/- 0.080)
      liter/kg of body weight for Asian, Hispanic, and Caucasian populations,
      respectively (P > 0.10). The KS means +/- standard deviations were 0.00424 +/-
      0.00129, 0.00404 +/- 0.00160 and 0.00394 0.00103 [h(ml/min/1.73 m2)]-1 +/- for
      Hispanic, Asian, and Caucasian populations, respectively. Again, there was no
      statistical difference among the groups (P > 0.10). In conclusion, there are no
      differences in aminoglycoside pharmacokinetics among Asian, Hispanic, and
      Caucasian patients.

PMID- 7811022
TI  - Cloning and expression of a cloxacillin-hydrolyzing enzyme and a cephalosporinase
      from Aeromonas sobria AER 14M in Escherichia coli: requirement for an E. coli
      chromosomal mutation for efficient expression of the class D enzyme.
AB  - Two beta-lactamase genes, asbA1 and asbB1, encoding AsbA1 and AsbB1,
      respectively, have been cloned from Aeromonas sobria AER 14M into Escherichia
      coli. AsbA1 was expressed at low but detectable levels in all E. coli laboratory
      cloning strains tested. AsbB1 was expressed well in the E. coli cloning strain
      DH5 alpha. However, no enzyme activity could be detected from the same clone when
      placed in E. coli MC1061. Ampicillin-resistant mutants of E. coli MC1061 were
      obtained that expressed high levels of enzymatically active AsbB1. Four
      independent mutants were examined. All four mutations mapped to one locus,
      designated blpA (beta-lactamase permissive). The blpA locus was distinct from
      other known loci that play a role in beta-lactamase expression, i.e., the two
      loci that affect expression of the Bacteroides fragilis metallo-beta-lactamase
      and the ampC regulatory genes, ampD, ampE, and ampG. Sequence analysis of asbA1
      and asbB1 revealed that AsbA1 was a class C beta-lactamase most closely related
      to the Pseudomonas aeruginosa chromosomal cephalosporinase and probably
      represents the common A. sobria cephalosporinase. AsbB1 was a class D enzyme most
      closely related to the oxacillin-hydrolyzing enzyme OXA-1, with 34% amino acid
      sequence identity. Purified AsbA1 was a typical cephalosporinase with a substrate
      profile that reflected high rates of hydrolysis of cephaloridine compared with
      benzylpenicillin. Purified AsbB1 showed strong penicillinase activity, with
      hydrolysis rates for carbenicillin and cloxacillin 2 to 2.5 times that for
      benzylpenicillin. Hydrolysis of imipenem was < or = 1% of that for
      benzylpenicillin. Both clavulanic acid and tazobactam strongly inhibited AsbB1,
      while sulbactam inhibited the AsbB1 enzyme less effectively. None of the
      inhibitors worked well against the AsbA1 enzyme. The chelators EDTA and 1,10-o
      phenanthroline did not affect the activity of either enzyme. A. sobria AER 14M
      was found to produce both a group 1 cephalosporinase and a novel group 2d
      cloxacillin-hydrolyzing beta-lactamase that has been designated here OXA-12.

PMID- 7811024
TI  - Analysis by PCR and direct DNA sequencing of gyrA mutations associated with
      fluoroquinolone resistance in Enterococcus faecalis.
AB  - A region of gyrA, the gene encoding subunit A of DNA gyrase, that is known to be
      associated with resistance was amplified and sequenced from 16 Enterococcus
      faecalis and Enterococcus faecium isolates. Six ciprofloxacin-resistant clinical
      isolates (MICs of ciprofloxacin, 32 to 64 micrograms/ml) and one multistep
      resistant laboratory mutant of E. faecalis (MIC of ciprofloxacin, 128
      micrograms/ml) contained a change from serine to arginine or to isoleucine at
      codon 83 or a change from glutamic acid to lysine or to glycine at codon 87
      (Escherichia coli GyrA coordinates); these changes have been associated with
      fluoroquinolone resistance in other species. No difference in the region studied
      was found in two ciprofloxacin-resistant E. faecium isolates (MICs, 32
      micrograms/ml) or in four laboratory derived, spontaneous ciprofloxacin-resistant
      mutants of E. faecalis (MICs, 8 to 16 micrograms/ml), suggesting that other
      mechanisms may be responsible for fluoroquinolone resistance in some enterococci.

PMID- 7811023
TI  - Antiprotozoal activities of benzimidazoles and correlations with beta-tubulin
      sequence.
AB  - Benzimidazoles have been widely used since the 1960s as anthelmintic agents in
      veterinary and human medicine and as antifungal agents in agriculture. More
      recently, selected benzimidazole derivatives were shown to be active in vitro
      against two protozoan parasites, Trichomonas vaginalis and Giardia lamblia, and
      clinical studies with AIDS patients have suggested that microsporidia are
      susceptible as well. Here, we first present in vitro susceptibility data for T.
      vaginalis and G. lamblia using an expanded set of benzimidazole derivatives. Both
      parasites were highly susceptible to four derivatives, including mebendazole,
      flubendazole, and fenbendazole (50% inhibitory concentrations of 0.005 to 0.16
      microgram/ml). These derivatives also had lethal activity that was time
      dependent: 90% of T. vaginalis cells failed to recover following a 20-h exposure
      to mebendazole at 0.17 microgram/ml. G. lamblia, but not T. vaginalis, was highly
      susceptible to five additional derivatives. Next, we examined in vitro activity
      of benzimidazoles against additional protozoan parasites: little or no activity
      was observed against Entamoeba histolytica, Leishmania major, and Acanthamoeba
      polyphaga. Since the microtubule protein beta-tubulin has been identified as the
      benzimidazole target in helminths and fungi, potential correlations between
      benzimidazole activity and beta-tubulin sequence were examined. This analysis
      included partial sequences (residues 108 to 259) from the organisms mentioned
      above, as well as the microsporidia Encephalitozoon hellem and Encephalitozoon
      cuniculi and the sporozoan Cryptosporidium parvum. beta-tubulin residues Glu-198
      and, in particular, Phe-200 are strong predictors of benzimidazole
      susceptibility; both are present in Encephalitozoon spp. but absent in C. parvum.

PMID- 7811025
TI  - Dissociated resistance among fluoroquinolones.
AB  - A panel of 190 clinical isolates of staphylococci, enterococci, Streptococcus
      pneumoniae, members of the family Enterobacteriaceae, and nonfermentative gram
      negative bacilli were examined by agar dilution tests for susceptibility to five
      quinolones and six nonquinolone agents. Members of the family Enterobacteriaceae
      and staphylococci were divided into subgroups according to their ciprofloxacin
      susceptibilities and were analyzed for cross-resistance to OPC-17116, ofloxacin,
      and temafloxacin. Although the MICs of all quinolones increased with increasing
      ciprofloxacin resistance, the MICs of OPC-17116, ofloxacin, and temafloxacin
      tended to increase less than those of ciprofloxacin, indicating that these agents
      were less affected by the mechanisms of quinolone resistance. An exception to
      this was the activity of OPC-17116 against highly ciprofloxacin-resistant
      staphylococci (MIC, > or = 8 micrograms/ml). Some of these staphylococci were
      equally resistant to OPC-17116, while others were fourfold more susceptible to
      ciprofloxacin than to OPC-17116. This indicated that in some strains OPC-17116
      was more affected than ciprofloxacin by certain mechanisms responsible for high
      level resistance. This was paralleled in single-step mutational studies in which
      7 of 19 staphylococcal mutants exhibited large decreases in susceptibility to OPC
      17116 (128- to 256-fold) but only modest decreases in susceptibility (4- to 16
      fold) to the other quinolones. Such mutants were selected only from strains
      moderately resistant to ciprofloxacin (MIC, > or = 1 microgram/ml). This
      heterogeneity in the resistance of staphylococci to fluoroquinolones has not been
      seen previously and suggests that certain mechanisms of resistance in
      staphylococci affect OPC-17116 to a much greater extent than other quinolones.

PMID- 7811026
TI  - Effect of enteral feeding with ensure on oral bioavailabilities of ofloxacin and
      ciprofloxacin.
AB  - The relative oral bioavailabilities of ciprofloxacin and ofloxacin when they were
      coadministered with water or an enteral feeding product (Ensure) were assessed in
      13 healthy volunteers. The area under the concentration time curve from time zero
      to infinity and the maximum concentration of drug in serum for both drugs were
      reduced by Ensure in comparison with those by water (P < 0.01). However, Ensure
      reduced the percent relative bioavailability of ciprofloxacin (72% +/- 14%;
      range, 52 to 96%) significantly more than ofloxacin (90% +/- 8.3%; range, 74 to
      105%) (P < 0.005). Coadministration of Ensure significantly diminished
      ciprofloxacin and ofloxacin absorption, but ciprofloxacin absorption was reduced
      significantly more than ofloxacin absorption.

PMID- 7811027
TI  - In vitro activities of metronidazole and its hydroxy metabolite against
      Bacteroides spp.
AB  - Metronidazole is metabolized to two major oxidative products: an acid metabolite
      and a hydroxy metabolite. While the activity of the acid metabolite is
      negligible, the activity of the hydroxy metabolite is approximately 65% of the
      activity of the parent drug. Pharmacokinetic studies of metronidazole and its
      hydroxy metabolite have shown that the MICs of both compounds remain above the
      MICs for most anaerobic organisms over an 8-h dosing interval. By a checkerboard
      assay, the combined activities of metronidazole and the hydroxy metabolite were
      examined against 4 quality control strains of Bacteroides species. Macrobroth
      tube dilutions were set up with Wilkins-Chalgren broth. Serial twofold dilutions
      of each agent were performed to achieve final concentrations ranging from 0.06 to
      4.0 micrograms/ml. The MICs for Bacteroides fragilis and B. distasonis were 1.0
      microgram/ml for both parent drug and metabolite. For B. thetaiotamicron and B.
      ovatus, the MICs of metronidazole and the hydroxy metabolite were 1.0 and 2.0
      micrograms/ml, respectively. Synergy was determined by calculating the fractional
      inhibitory concentration (FIC) index. The interpretative criteria for the FIC
      index were as follows: synergy, FIC < or = 0.5; partial synergy, 0.51 to 0.75;
      indifference, FIC 0.76 to 4.0; and antagonism, FIC > 4.0. Partial synergy was
      observed for the four anaerobes tested, with FIC indices ranging from 0.63 to
      0.75. On the basis of this data, in vitro susceptibilities to agents such as
      metronidazole may ultimately require reevaluation to account for active
      metabolites.

PMID- 7811028
TI  - Pharmacokinetics of fluconazole in cerebrospinal fluid and serum of rabbits:
      validation of an animal model used to measure drug concentrations in
      cerebrospinal fluid.
AB  - Complete concentration-time data describing the pharmacokinetics of fluconazole
      in the cerebrospinal fluid (CSF) following a single dose are not available for
      humans or animals. We studied the pharmacokinetics of fluconazole with an
      indwelling intracisternal needle as described by R.G. Dacey and M.A. Sande
      (Antimicrob. Agents Chemother. 6:437-441, 1974). To determine whether the
      presence of an intracisternal needle alters pharmacokinetics in the CSF, we
      validated this model with uninfected rabbits by measuring pharmacokinetic
      constants following direct intracisternal and intravenous administration of
      fluconazole. Following direct injection, there was no alteration of elimination
      rates in the CSF with increasing sample number or time. Following intravenous
      administration, the penetration and kinetic constants were the same in individual
      animals from which multiple CSF samples were obtained as in a composite subject
      constructed by pooling virgin samples from different animals. The presence of the
      intracisternal needle did not alter CSF chemistry or leukocyte counts, and
      erythrocyte contamination was < 0.001%. While drug concentrations were measured
      by a microbiological assay, we also compared the sensitivity and reproducibility
      of a high-performance liquid chromatography (HPLC) assay with those of the
      microbiological assay. Following a single intravenous dose, the maximum
      concentration of the drug in serum, the time to maximum concentration of the drug
      in serum, the terminal elimination half-life in the CSF, and the percent
      penetration by fluconazole were 6.12 micrograms/ml, 1 h, 9.0 h, and 84.3%,
      respectively. We conclude that the sampling of CSF via an indwelling needle does
      not alter fluconazole pharmacokinetics, cause inflammation, or alter chemical
      parameters; that the microbiological assay is at least equivalent in sensitivity
      and reproducibility to the HPLC assay; and that robust parameters describing the
      pharmacokinetics of fluconazole are possible with this model.

PMID- 7811029
TI  - Contribution of enzymatic properties, cell permeability, and enzyme expression to
      microbiological activities of beta-lactams in three Bacteroides fragilis isolates
      that harbor a metallo-beta-lactamase gene.
AB  - The metallo-beta-lactamase gene, ccrA, has been cloned from three clinical
      isolates of Bacteroides fragilis, TAL3636, QMCN3, and QMCN4. Although all three
      isolates harbored a gene encoding a potent beta-lactamase, the MICs of
      benzylpenicillin, piperacillin, cefotaxime, ceftazidime, imipenem, and biapenem
      for the three isolates varied from 4- to > 128-fold. QMCN4 was the most
      susceptible of the three isolates, followed by QMCN3. TAL3636 was resistant to
      all of the beta-lactams. Previous DNA sequence analysis of the three ccrA genes
      revealed that the enzymes differed at 5 amino acid residues (B. A. Rasmussen, Y.
      Gluzman, and F. P. Tally, Mol. Microbiol. 5:1211-1219, 1991). Biochemical
      characterization of the three enzymes revealed only small differences in kcat and
      Km values for the majority of beta-lactams tested. Thus, the 5 amino acid
      substitutions affected the hydrolyzing activity of the enzymes only modestly.
      Crypticity differences between the three isolates showed that QMCN4 was the least
      permeable of the isolates to cephaloridine, followed by TAL3636, and that QMCN3
      was highly permeable to cephaloridine. Therefore, neither catalytic activity nor
      permeability was a major contributor to the dramatic differences in the MICs.
      Instead, microbiological susceptibility was closely related to the level of
      metallo-beta-lactamase present in each isolate. Both biochemical and physical
      studies indicated that TAL3636 produced 5- to 10-fold and 50- to 100-fold more
      metallo-beta-lactamase than QMCN3 and QMCN4, respectively. Therefore, the level
      of CcrA enzyme production is the dominant contributing factor to high-level
      resistance among strains harboring a ccrA gene.

PMID- 7811030
TI  - Antimicrobial susceptibility of pathogenic Yersinia enterocolitica isolated in
      Canada from 1972 to 1990.
AB  - Yersinia enterocolitica has emerged as an enteropathogen associated with several
      types of human infections that often require antimicrobial therapy, but little is
      known about the antimicrobial susceptibilities of pathogenic strains isolated
      from humans in Canada. To determine the present patterns of antimicrobial
      susceptibility, to identify changes in these patterns that occurred during the
      past two decades, and to investigate the relationships between O serotypes and
      patterns of susceptibility, we tested a total of 1,105 pathogenic Y.
      enterocolitica strains isolated during 1972 to 1976, 1980, 1985, and 1990 for
      their susceptibilities to 22 antimicrobial agents. Susceptibility testing was
      performed by using a single breakpoint concentration in agar procedure. The
      results showed that all strains were susceptible to ciprofloxacin and
      piperacillin, and 98% or more of the strains from each period were susceptible to
      trimethoprim, sulfamethoxazole, cotrimoxazole, tetracycline, chloramphenicol,
      cefamandole, cefotaxime, aztreonam, and four aminoglycosides. In contrast, all
      strains were nonsusceptible to erythromycin, furazolidone, and clindamycin and
      90% or more of the strains from each period were nonsusceptible to ampicillin,
      carbenicillin, ticarcillin, and cephalothin. Strains belonging to serotypes O:3,
      O:5,27, and O:8 had different patterns of susceptibility to ampicillin,
      carbenicillin, ticarcillin, and amoxicillin-clavulanic acid. No major difference
      in susceptibility was observed between any of the groups of human or animal
      strains included in the study, but nonsusceptibility to tetracycline increased
      from 0.4% in 1985 to 2% in 1990 in human strains isolated in those years. Our
      results indicate that between 1972 and 1990 there was no marked decrease in
      susceptibility to agents commonly used for therapy among pathogenic Y.
      enterocolitica strains isolated in Canada.

PMID- 7811031
TI  - Investigation of ciprofloxacin penetration into Pseudomonas aeruginosa biofilms.
AB  - Bacterial infections associated with indwelling medical devices often demonstrate
      an intrinsic resistance to antimicrobial therapies. In order to explore the
      possibility of transport limitation to biofilm bacteria as a contributing factor,
      the penetration of a fluoroquinolone antibiotic, ciprofloxacin, through
      Pseudomonas aeruginosa biofilms was investigated. Attenuated total reflection
      Fourier transform infrared (ATR/FT-IR) spectrometry was employed to monitor
      bacterial colonization of a germanium substratum, transport of ciprofloxacin to
      the biofilm-substratum interface, and interaction of biofilm components with the
      antibiotic in a flowing system. Transport of the antibiotic to the biofilm
      substratum interface during the 21-min exposure to 100 micrograms/ml was found to
      be significantly impeded by the biofilm. Significant changes in IR bands of the
      biofilm in regions of the spectrum associated with RNA and DNA vibrational modes
      appeared following exposure to the antibiotic, indicating chemical modification
      of biofilm components. These results suggest that transport limitations may be an
      important factor in the antimicrobial resistance of biofilm bacteria and that
      ATR/FT-IR spectrometry may be used to follow the time course of antimicrobial
      action in biofilms in situ.

PMID- 7811032
TI  - Sensitive and specific radioimmunoassay for fialuridine: initial assessment of
      pharmacokinetics after single oral doses to healthy volunteers.
AB  - Fialuridine (FIAU) is a halogen-substituted analog of thymidine that was
      undergoing clinical investigation as a drug for the treatment of chronic
      hepatitis B viral infection. However, clinical trials of FIAU were terminated
      after adverse events occurred following chronic oral administration. Prior to the
      termination of clinical trials, a sensitive assay was needed for the measurement
      of FIAU because of the anticipated low dose administered to patients. We
      therefore undertook the development of a radioimmunoassay (RIA). A specific
      antiserum was raised in rabbits following immunization with a 5'-O-hemisuccinate
      analog of FIAU coupled to keyhole limpet hemocyanin. Radiolabeled FIAU was
      synthesized by a destannylation procedure by using sodium [125I]iodide. We
      developed a competitive-binding procedure and used precipitation with
      polyethylene glycol as the method for separating the bound and free forms of
      FIAU. The RIA is sensitive (0.2 ng/ml), specific (negligible interference from
      known metabolites and endogenous nucleosides), and reproducible (interassay
      coefficients of variation range from 5 to 19.7% for serum controls). We used the
      RIA to assess the pharmacokinetics of FIAU in healthy adult volunteers following
      administration of a single 5-mg oral dose. The sensitivity of the RIA permitted
      the detection of a prolonged elimination phase for FIAU in healthy volunteers and
      dogs, with mean elimination half-lives of 29.3 and 35.3 h, respectively. We
      conclude the RIA is a valid method for the quantification of FIAU in biological
      fluids.

PMID- 7811033
TI  - Biochemical properties of inducible beta-lactamases produced from Xanthomonas
      maltophilia.
AB  - Four different beta-lactamases have been found in several strains of Xanthomonas
      maltophilia isolated from blood cultures during 1984 to 1991 at the Edinburgh
      Royal Infirmary. One was a metallo-beta-lactamase with predominantly
      penicillinase activity and an isoelectric point of 6.8. Its molecular size as
      determined by gel filtration was 96 kDa but was only 26 kDa by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), suggesting a tetramer of
      four equal subunits. The enzyme hydrolyzed all classes of beta-lactams except the
      monobactam aztreonam. This enzyme was not inhibited by potassium clavulanate or
      BRL 42715 but was inhibited by p-chloromercuribenzoate, mercuric chloride, and
      EDTA. The beta-lactamase was unstable in 50 mM sodium phosphate buffer (pH 8.0)
      but stable in 50 mM Tris HCl (pH 8.0). The other beta-lactamases focused as a
      series of different isoelectric points, ranging from pI 5.2 to 6.6. Together,
      these enzymes exhibited a broad spectrum of activity, hydrolyzing most classes of
      beta-lactams but not imipenem or aztreonam. Their molecular size was 48 kDa by
      Sephadex gel filtration and 24 kDa by SDS-PAGE, indicating that they were enzymes
      consisting of two equal subunits. They were inhibited by p-chloromercuribenzoate,
      mercuric chloride, potassium clavulanate, and BRL 42715 but not EDTA. This study
      demonstrated that X. maltophilia produces more than just the L1 and L2 beta
      lactamases.

PMID- 7811034
TI  - Gene sequence and biochemical characterization of FOX-1 from Klebsiella
      pneumoniae, a new AmpC-type plasmid-mediated beta-lactamase with two molecular
      variants.
AB  - Klebsiella pneumoniae BA32, a clinical isolate from Buenos Aires, Argentina, was
      found to produce a plasmid-encoded beta-lactamase (FOX-1) which conferred
      resistance to broad-spectrum cephalosporins and cephamycins. Resistance could be
      transferred by conjugation or transformation into Escherichia coli K-12 via a
      48.5-kb plasmid (pGLK1) that produced two FOX-1 molecular variants with
      isoelectric points of 6.8 and 7.2 and apparent molecular sizes of 37 and 35 kDa,
      respectively. The kinetic study revealed that the two variants had very similar
      substrate and inhibition profiles. These values resemble those of chromosomally
      mediated class C (group 1) cephalosporinases. The structural gene of FOX-1
      (blaFOX-1) was cloned into a 2,270-bp PstI-PstI fragment and was expressed in E.
      coli TG1. The deduced 382-amino-acid sequence of FOX-1 exhibited a high degree of
      similarity with chromosomally encoded AmpC beta-lactamases of Pseudomonas
      aeruginosa, Serratia marcescens, Enterobacter cloacae, E. coli, and Citrobacter
      freundii. These findings suggest that FOX-1 is a plasmid-mediated AmpC-type beta
      lactamase that is encoded by a single gene and that has two molecular variants.

PMID- 7811035
TI  - Effect of macrophage colony-stimulating factor on anticryptococcal activity of
      bronchoalveolar macrophages: synergy with fluconazole for killing.
AB  - The anticryptococcal activity of murine bronchoalveolar macrophages (BAM) and
      their synergy with fluconazole (FCZ) was studied. BAM cultured with tissue
      culture medium for 48 to 72 h were fungicidal (24 to 39%) in a 3-h killing assay.
      However, net killing of Cryptococcus neoformans did not continue when culture
      time was extended to 24 h, although BAM were fungistatic (88 to 98%). Treatment
      with macrophage colony-stimulating factor (M-CSF; 5,000 U/ml, 48 h) did not
      significantly increase BAM killing of a low challenge dose in 3-h assays compared
      with control BAM. However, M-CSF-treated BAM were significantly more fungistatic
      against higher challenge doses in the 3-h assays. FCZ was not fungicidal at 5
      micrograms/ml but was highly fungistatic (98 and 99% at 24 and 48 h,
      respectively). M-CSF-treated BAM acted synergistically with FCZ (2.5
      micrograms/ml) for significantly greater killing than control BAM, 55% versus 20%
      and 96% versus 45% at 24 h and 48 h, respectively. Killing by M-CSF BAM and FCZ
      (5.0 micrograms/ml) was significantly (P < 0.01) greater than that by control BAM
      and FCZ at 48 h. These findings indicate an important collaborative role for BAM
      and FCZ in killing C. neoformans, and this is enhanced by M-CSF.

PMID- 7811036
TI  - Effect of in vivo macrophage colony-stimulating factor on fungistasis of
      bronchoalveolar and peritoneal macrophages against Cryptococcus neoformans.
AB  - Macrophage colony-stimulating factor (M-CSF) given subcutaneously at a dose of
      2.5 mg/kg of body weight (4.75 x 10(6) U/kg) to CD-1 male mice 8 to 12 weeks old
      was found to enhance significantly the fungistasis of bronchoalveolar macrophages
      (BAM) against Cryptococcus neoformans. When M-CSF was given 1, 3, 7, 9, or 13
      days before an ex vivo challenge with C. neoformans, fungistasis was increased (P
      ranged from < 0.05 to < 0.001) compared with that induced by control BAM. A
      maximum effect was seen by days 1 and 3 after administration of M-CSF. Twenty-one
      days after M-CSF, BAM did not produce significantly enhanced fungistasis. M-CSF
      also significantly enhances the fungistatic effect of peritoneal macrophages (PM)
      if given 1, 3, and 7 days prior to testing against C. neoformans in comparison
      with control PM (P ranged from < 0.05 to < 0.001). PM did not produce enhanced
      fungistasis 9 or 13 days after administration of M-CSF. These studies
      demonstrating in vivo enhancement of anticryptococcal activity of macrophages
      with M-CSF provide a rationale for in vivo use of M-CSF to enhance resistance to
      infection with C. neoformans.

PMID- 7811037
TI  - Nucleotide analogs related to acyclovir and ganciclovir are effective against
      murine cytomegalovirus infections in BALB/c and severe combined immunodeficient
      mice.
AB  - Acyclovir phosphonate [9-(3-phosphono-propyloxymethyl)guanine; SR3722] and the S
      enantiomer (SR3772), R enantiomer (SR3773), and R,S enantiomeric mixture
      (SR3745A) of ganciclovir phosphonate (9-[((+/-)-1-hydroxymethyl-3
      phosphono)propyloxymethyl]guanine) were evaluated for their antiviral activities
      against murine cytomegalovirus. In severe combined immunodeficient mice infected
      with murine cytomegalovirus, SR3773 and SR3745A (12.5, 25, and 50 mg/kg of body
      weight per day) were superior to ganciclovir in extending the mean time to death,
      whereas SR3722 and SR3772 was less potent than ganciclovir. In normal BALB/c
      mice, SR3773 and ganciclovir were approximately equally active in preventing
      death. SR3773 caused renal tubular damage when administered at 50 mg/kg/day for
      15 days. These results suggest that SR3773 may have potential for use in the
      treatment of human cytomegalovirus infections, but it may also exhibit renal
      toxicity.

PMID- 7811038
TI  - Pig kidney (LLC-PK1) cell membrane fluidity during exposure to gentamicin or
      tobramycin.
AB  - The surface membrane properties of LLC-PK1 cells grown with and without various
      amounts of gentamicin or tobramycin for various lengths of time were determined
      by measuring the diffusion coefficient of N-(7-nitrobenz-2-oxa-1,3-diazol-4
      yl)dipalmitoyl-L- alpha-phosphatidylethanolamine (NBD-PE) and the percentage of
      NBD-PE free to diffuse after photobleaching. One hour of exposure to tobramycin
      decreased the percentage that was free to diffuse. After 1 day or longer of
      exposure to either aminoglycoside the percentage that was free to diffuse
      returned to preexposure levels and the diffusion coefficient decreased.

PMID- 7811039
TI  - Pure nucleoside enantiomers of beta-2',3'-dideoxycytidine analogs are selective
      inhibitors of hepatitis B virus in vitro.
AB  - (-)-beta-L-2',3'-Dideoxycytidine (beta-L-DDC), (+)-beta-D-2',3'-dideoxycytidine
      (beta-D-DDC), (-)-beta-L-2',3'-dideoxy-5-fluorocytidine (beta-L-FDDC), (-)-beta-L
      2',3'-dideoxy-5-fluoro-3'-thiacytidine (beta-L-FTC), and (+)-beta-D-1,3-dioxolane
      5-fluorocytidine (beta-D-FDOC) were evaluated for their anti-hepatitis B virus
      (anti-HBV) activities in HBV-transfected human liver cells (2.2.15). The order of
      decreasing potency for the compounds at the 90% effect level was beta-D-FDOC >
      beta-L-FTC > beta-L-FDDC approximately beta-L-DDC >> beta-D-DDC. Inhibition of
      HBV in transfected liver cells by the cytosine nucleosides was selective. The
      beta-L-nucleoside-5'-triphosphates were consistently more potent inhibitors of
      woodchuck hepatitis virus DNA polymerase than the corresponding natural beta-D
      enantiomers.

PMID- 7811040
TI  - Substrate specificity of Epstein-Barr virus thymidine kinase.
AB  - Purified recombinant protein encoded by the BXLF-I open reading frame of the
      Epstein-Barr virus genome has thymidine kinase activity. The substrate behaviors
      of various nucleosides toward this enzyme were tested. Halogenated deoxyuridines,
      zidovudine, and bromovinyldeoxyuridine are efficient substrates, while acyclovir
      and dihydroxypropylmethylguanine are relatively poor substrates for the Epstein
      Barr virus thymidine kinase.

PMID- 7811041
TI  - Inhibitory effects of acyclic nucleoside phosphonates on human hepatitis B virus
      and duck hepatitis B virus infections in tissue culture.
AB  - The inhibitory effects of the 9-(2-phosphonylmethoxyethyl)adenine-related
      compounds (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)-adenine, (S)-9-(3-fluoro-2
      phosphonylmethoxypropyl)adenine, (R)-9-(2-phosphonylmethoxypropyl)adenine, (R)-9
      (2-phosphonylmethoxypropyl)-2,6-diaminopurine, and (S)-1-(3-hydroxy-2
      phosphonylmethoxypropyl)cytosine on human hepatitis B virus replication in the
      human hepatoma cell line HepG2 2.2.15 and duck hepatitis B virus infection in
      primary duck hepatocytes were investigated. (R)-9-(2-phosphonylmethoxypropyl-2,6
      diaminopurine had the lowest 50% inhibitory concentrations against hepatitis B
      virus and duck hepatitis B virus, 0.22 and 0.06 microM, respectively, i.e., two-
      to fivefold lower concentrations than required for (R)-9-(2
      phosphonylmethoxypropyl)adenine and 9-(2-phosphonylmethoxyethyl)adenine. All
      compounds were not toxic in vitro at a concentration of 100 microM.

PMID- 7811042
TI  - Antibiotic resistance and penicillin tolerance in clinical isolates of group B
      streptococci.
AB  - The aim of this study was to determine the susceptibility patterns of 100 group B
      streptococcal strains isolated in our hospital and to ascertain tolerance to
      penicillin by determining quantitative killing curves. We found two strains with
      intermediate susceptibility to penicillin and eight strains to ampicillin.
      Seventeen isolates were tolerant to penicillin, with bacterial counts decreasing
      2 to 3 log during the first 8 h but still above 10(2) CFU/ml after 24 h. The
      kinetic study shows that penicillin tolerance is not rare among group B
      streptococci isolated in our hospital.

PMID- 7811043
TI  - Effect of bismuth subsalicylate on ciprofloxacin bioavailability.
AB  - A single oral dose of 528 mg of bismuth subsalicylate (30 ml of Pepto-Bismol) had
      no significant effect on the plasma pharmacokinetics of a single oral dose of 750
      mg of ciprofloxacin administered to 12 healthy volunteers (six men and six
      women). These results suggest that ciprofloxacin bioavailability will not be
      significantly decreased by single doses of bismuth subsalicylate when the two
      medications are administered simultaneously.

PMID- 7811044
TI  - Failure of time-kill synergy studies using subinhibitory antimicrobial
      concentrations to predict in vivo antagonism of cephalosporin-rifampin
      combinations against Staphylococcus aureus.
AB  - Results of in vitro time-kill synergy studies using subinhibitory, inhibitory, or
      suprainhibitory concentrations of bactericidal agents were compared with
      treatment outcomes of experimental infective endocarditis due to a methicillin
      susceptible strain of Staphylococcus aureus. For rifampin-cephalosporin
      combinations, in vitro synergy testing using recommended fractions of the MIC
      failed to predict antagonism in vivo while concentrations above the MIC
      corresponded with antagonism in vivo.

PMID- 7811045
TI  - Persistence of Neisseria gonorrhoeae strains with decreased susceptibilities to
      ciprofloxacin and ofloxacin in Cleveland, Ohio, from 1992 through 1993.
AB  - Twenty-five isolates of beta-lactamase-negative strains of Neisseria gonorrhoeae
      exhibiting decreased susceptibilities to ciprofloxacin (MIC, > or = 0.125
      microgram/ml) were isolated from men with uncomplicated gonococcal urethritis in
      Cleveland, Ohio, from January 1992 through June 1993. The strains belonged to
      three auxotype-serovar classes: Pro-IB-1 (2 isolates), Pro-IB-2 (21 isolates),
      and Pro-IB-3 (2 isolates). MICs for strains were in the intermediate or resistant
      categories for penicillin, the intermediate or susceptible categories for
      tetracycline (with the exception of one strain that had acquired the 25.2-MDa
      TetM-containing plasmid) and cefoxitin, and the susceptible categories for
      ceftriaxone and cefixime (MICs, < or = 0.25 microgram/ml) and spectinomycin (MIC,
      < or = 256 micrograms/ml). MICs for strains were also in the susceptible category
      for ofloxacin (MIC, 0.25 microgram/ml) and in categories higher than susceptible
      for ciprofloxacin (MICs, 0.125 to 0.25 microgram/ml) and ofloxacin (MIC, 0.5
      microgram/ml). The diameters of zones of inhibition for these strains ranged from
      31 to 39 mm for ciprofloxacin to 28 to 35 mm for ofloxacin. The persistence of
      these strains over an 18-month period supports the need for routine sentinel
      surveillance and monitoring of gonococcal isolates, particularly posttreatment
      isolates, for resistance to quinolones when these agents are used for the primary
      therapy of uncomplicated gonorrhea.

PMID- 7811046
TI  - Inactivation of the macrolide antibiotics erythromycin, midecamycin, and
      rokitamycin by pathogenic Nocardia species.
AB  - A survey of five Nocardia spp. with respect to susceptibility towards three
      macrolides (erythromycin, rokitamycin, and midecamycin) showed that the Nocardia
      spp. have different susceptibility profiles. Most of the resistance was due to
      the inactivation of the macrolides by phosphorylation, glycosylation, reduction,
      deacylation, or a combination thereof.

PMID- 7811047
TI  - Emerging in vitro resistance to quinolones in penicillinase-producing Neisseria
      gonorrhoeae strains in Hawaii.
AB  - The susceptibilities of 37 penicillinase-producing strains of Neisseria
      gonorrhoeae (PPNG), isolated in Hawaii from December 1991 through January 1994,
      were determined to ciprofloxacin and ofloxacin, fluoroquinolone agents currently
      recommended by the Centers for Disease Control and Prevention as alternative
      regimens for the treatment of uncomplicated gonorrhea. Nine isolates (24.3%)
      exhibited decreased susceptibilities (MICs, > or = 0.06 microgram/ml) to
      ciprofloxacin and ofloxacin. Ciprofloxacin MICs for three isolates (8.1%) were
      2.0 micrograms/ml; these isolates belonged to the auxotype/serovar class Pro/IB-7
      and possessed the 3.2-MDa beta-lactamase and the 24.5-MDa conjugative plasmids.
      Six strains for which ciprofloxacin MICs were 0.06 to 0.125 microgram/ml belonged
      to a variety of gonococcal phenotypes. Strains for which ciprofloxacin MICs were
      2.0 micrograms/ml were isolated from persons who had traveled to, or were sexual
      contacts of persons who had recently traveled to, Southeast Asia. Persons
      infected with these isolates had been treated with ceftriaxone (250 mg
      intramuscularly, single dose); therefore, none of these cases were associated
      with clinical failure following the use of fluoroquinolone therapy. Further
      studies are needed to confirm the clinical and public health significance of
      increased in vitro resistance to ciprofloxacin and ofloxacin in N. gonorrhoeae.

PMID- 7811048
TI  - Therapeutic efficacy of lanoconazole, a new imidazole antimycotic agent, for
      experimental cutaneous candidiasis in guinea pigs.
AB  - The therapeutic efficacy of 1% cream and 1% solution of lanoconazole, a new
      imidazole antimycotic agent, in the model of cutaneous candidiasis in
      prednisolone-treated guinea pigs was evaluated in comparison with that of
      comparable formulations of bifonazole. Each preparation was topically applied
      once a day for 3 consecutive days, starting on the fifth day postinfection, and
      quantitative culture study wsa conducted on the ninth day postinfection. Both
      formulations of lanoconazole were much more highly effective in terms of
      eradication of fungi than the bifonazole formulations.

PMID- 7811049
TI  - Nucleotide sequence of a plasmid-mediated cephalosporinase gene (blaLAT-1) found
      in Klebsiella pneumoniae.
AB  - The nucleotide sequence of the gene encoding a novel cephalosporinase (LAT-1),
      carried by a non-self-transferable plasmid from Klebsiella pneumoniae, has been
      determined. It was found that the sequence shares a high degree of homology with
      the Citrobacter freundii OS60 ampC structural gene.

PMID- 7811050
TI  - Penetration of cefprozil into middle ear fluid of patients with otitis media.
AB  - Penetration of cefprozil into the middle ear fluid was investigated in patients
      with chronic otitis media. A total of 89 patients ranging from 7 months to 11
      years old participated in the study. The middle ear fluid was removed by
      ventilation tubes inserted through the tympanic membrane at times ranging from
      0.38 to 5.97 h after oral administration of a single dose of 15 or 20 mg/kg of
      body weight. A blood sample was also collected as soon as the middle ear fluid
      was removed. Plasma samples were analyzed for the concentration of cefprozil by a
      high-performance liquid chromatographic assay. Middle ear fluid samples were
      analyzed for the concentration of cefprozil by a microbiological assay. The
      concentrations of cefprozil in plasma ranged from 0.38 to 15.97 micrograms/ml at
      the 15-mg/kg dose level and from 1.28 to 21.47 micrograms/ml at the 20-mg/kg dose
      level. The corresponding middle ear fluid concentrations of cefprozil ranged from
      0.06 to 4.44 micrograms/ml and from 0.17 to 8.67 micrograms/ml, respectively.
      Cefprozil penetrates well into middle ear fluid in patients with chronic otitis
      media.

PMID- 7811051
TI  - In vitro activity of dirithromycin against Chlamydia trachomatis.
AB  - Dirithromycin is a new macrolide antibiotic with an active metabolite,
      erythromycylamine. We evaluated the in vitro activities of both drugs against 16
      isolates of Chlamydia trachomatis and compared them with that of doxycycline. In
      vitro susceptibility testing was performed with McCoy cell monolayers. The MIC
      was defined as the lowest concentration of antibiotic without inclusions. The MBC
      was defined as the lowest concentration of antibiotic yielding no inclusions
      after passage onto 24-h-old antibiotic-free McCoy cell monolayers. Dirithromycin
      and erythromycylamine appeared to be equally effective against these 16 strains
      of C. trachomatis (MIC for 90% of strains tested, 1 mg/ml; MBC for 90% of strains
      tested, 2 micrograms/ml). Both were less active than doxycycline (MIC for 90% of
      strains tested, 0.06 micrograms/ml; MBC for 90% of strains tested, 0.12
      micrograms/ml). The combination of dirithromycin and erythromycylamine appeared
      to be additive.

PMID- 7811052
TI  - Low-dose dexamethasone as adjunctive therapy for disseminated Mycobacterium avium
      complex infections in AIDS patients.
AB  - Five human immunodeficiency virus-infected patients with disseminated
      Mycobacterium avium complex infection had progressive weight loss and persistent
      fever despite multidrug antimycobacterial therapy. These patients were given
      daily low-dose oral dexamethasone (typically 2 mg/day) as adjunctive therapy. All
      had substantial and sustained weight gain (12 to 50% of pre-steroid treatment
      body weight [P < 0.03]), reduction in fever, and an improved sense of well-being.
      The serum albumin level increased during dexamethasone therapy (from 3.06 +/-
      0.59 g/dl [mean +/- standard deviation] to 3.9 +/- 0.22 g/dl [P < 0.01]), while
      the serum alkaline phosphatase level fell (from 368 +/- 247 U/liter to 128 +/-
      43.6 U/liter [P < 0.04]). Further studies of the potential role for
      corticosteroids in the management of disseminated M. avium complex infections in
      human immunodeficiency virus-infected patients are warranted.

PMID- 7811053
TI  - N,N-dimethylglycyl-amido derivative of minocycline and 6-demethyl-6
      desoxytetracycline, two new glycylcyclines highly effective against tetracycline
      resistant gram-positive cocci.
AB  - The in vitro activities of the N,N-dimethylglycyl-amino derivative of minocycline
      (DMG-MINO) and 6-dimethyl-6-dexoxytetracycline (DMG-DMDOT), members of a new
      generation of tetracyclines, were evaluated by an agar dilution method and were
      compared with those of tetracycline and minocycline against 224 tetracycline
      resistant and 73 tetracycline-susceptible recent clinical isolates of gram
      positive cocci, including multiple-antibiotic-resistant methicillin-resistant
      Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae. The MICs
      of DMG-MINO and DMG-DMDOT were up to 500- to 2,000-fold lower than those of
      tetracycline against methicillin-resistant S. aureus and Streptococcus pneumoniae
      (MIC for 50% of strains tested [MIC50], < 0.06 microgram/ml). Against
      Streptococcus groups A, B, C, and G and Enterococcus faecalis, the MIC50 was 0.5
      microgram/ml. MIC50s were greater only for coagulase-negative staphylococci (2
      micrograms/ml). These data indicate that DMG-MINO and DMG-DMDOT are very potent
      drugs, and further in vitro and in vivo studies are warranted.

PMID- 7811054
TI  - Penetration of cefotetan into suction skin blister fluid and tissue homogenates
      in patients undergoing abdominal surgery.
AB  - The penetration of cefotetan (2-g intravenous bolus) into the suction blister
      fluid and tissue homogenates of 11 patients was investigated. Mean concentrations
      in tissue were significantly lower than contemporary suction blister fluid
      levels. These data show that the determination of beta-lactam concentrations by
      the tissue homogenate method may seriously underestimate the actual antibiotic
      levels in extracellular fluid.

PMID- 7811055
TI  - Concentrations in serum and distribution in tissue of free and liposomal
      amphotericin B in rats during continuous intralipid infusion.
AB  - The influences of Intralipid (IL) and 0.45% normal-saline infusions on the
      concentration in serum and distribution in tissue of amphotericin B (AmpB) and
      liposomal amphotericin B (L-AmpB) in rats were compared. In animals receiving a
      continuous IL infusion, concentrations of AmpB in kidneys and lungs were
      significantly higher, but the concentration of AmpB in serum was significantly
      lower in animals administered AmpB versus those given L-AmpB. In animals
      receiving a continuous normal-saline infusion concentrations of AmpB in kidneys
      and the spleen were significantly higher, but the concentration of AmpB in serum
      was significantly lower in animals administered AmpB versus those given L-AmpB.
      These results suggest that the increased total serum cholesterol and high-density
      lipoprotein cholesterol during the IL infusion decreased the clearance of AmpB
      from the bloodstream and decreased the L-AmpB concentration in the kidney and
      lung.

PMID- 7811057
TI  - Multiple drug effect analysis with confidence interval.
AB  - The development of mathematical models for determining antagonism, synergy or
      additivism for drug combinations is becoming increasingly important in medical
      research and medicine. This paper describes improvements in the Chou and Talalay
      method which provides for the first time confidence intervals for the combination
      index. The Monte Carlo technique was used to calculate the confidence intervals
      and to obtain the new parameters which are needed for the modified interaction
      diagnosis. This new method can be adapted to current as well as future formulae
      used to evaluate drug combinations. Programs written in Microsoft and Visual
      Basic were developed for use on commonly available personal computers which we
      call Combostat.

PMID- 7811056
TI  - Evaluation of effects of altered gastric pH on absorption of dapsone in healthy
      volunteers.
AB  - A prospective, randomized, crossover study was performed with seven healthy
      volunteers to address the effect of increased gastric pH on dapsone absorption.
      Subjects were randomized to receive a single 100-mg dose of dapsone or a single
      100-mg dose of dapsone in addition to 30 ml of a high potency antacid 1 h before
      dapsone administration and hourly thereafter for a total of 10 doses. Dapsone
      concentrations in serum were measured periodically for 48 h. No statistical
      differences between the two regimens were noted when mean dapsone maximal initial
      concentrations, times to peak, and areas under the curve were compared. These
      data suggest that an increase in gastric pH has little or no effect on the
      absorption of dapsone in healthy subjects.

PMID- 7811058
TI  - Synthesis and anti-HIV activity of thiocholesteryl-coupled phosphodiester
      antisense oligonucleotides incorporated into immunoliposomes.
AB  - Encapsulation of oligonucleotides in antibody-targeted liposomes
      (immunoliposomes) which bind to target cells permits intracellular delivery of
      the oligonucleotides. This approach circumvents problems of extracellular
      degradation by nucleases and poor membrane permeability which free phosphodiester
      oligonucleotides are subject to, but leaves unresolved the inefficiency of
      encapsulation of oligonucleotides in liposomes. We have coupled oligonucleotides
      to cholesterol via a reversible disulfide bond. This modification of
      oligonucleotides improved their association with immunoliposomes by a factor of
      about 10 in comparison to unmodified oligonucleotides. The presence of
      cholesteryl-modified oligonucleotides incorporated in the bilayer of liposomes
      did not interfere with the coupling of the targeting protein to the liposome
      surface. Free or cholesterol coupled oligonucleotides associated with liposomes
      and directed against the tat gene of HIV-1 were tested for inhibition of HIV-1
      proliferation in acutely infected cells. We demonstrate that the cholesteryl
      modified as well as unmodified oligonucleotides acquire the target specificity of
      the antibody on the liposome. Their antiviral activity when delivered into cells
      is sequence-specific. The activity of these modified or unmodified
      oligonucleotides to inhibit the replication of HIV was the same on an equimolar
      basis (EC50 around 0.1 microM). Cholesterol coupled oligonucleotides thus offer
      increased liposome association without loss of antiviral activity.

PMID- 7811059
TI  - Antiviral capsid-binding compounds can inhibit the adsorption of minor receptor
      rhinoviruses.
AB  - The effect of four structurally diverse capsid-binding compounds on the
      adsorption of seven human rhinoviruses (HRV), representative for both receptor
      and antiviral groupings was studied using infective center assays. Antiviral
      compounds studied included a pyridazinamine (R 61837), an isoxazole (WIN 51711),
      a flavan (4',6-dichloroflavan) and a chalcone (Ro-09410). Minor receptor viruses
      studied were HRV 1A, HRV 2 and HRV 29 (antiviral group B), major receptor viruses
      were HRV 9, HRV 39 and HRV 14, HRV 35 (antiviral group B and A, respectively).
      The adsorption of four out of the seven serotypes was inhibited by some antiviral
      compounds, but not by others, indicating that the conformational alterations
      induced by antiviral compounds can vary considerably within a given serotype,
      depending on the chemical nature of the antiviral compound used. A correlation
      between inhibition of adsorption and receptor grouping or antiviral grouping
      could not be found.

PMID- 7811060
TI  - In vitro inhibition of human cytomegalovirus replication by desferrioxamine.
AB  - Desferrioxamine (DFO) is commonly used in therapy as a chelator of ferric ion in
      disorders of iron overload. We found that DFO inhibits human cytomegalovirus
      (HCMV) replication in infected cultures of human foreskin fibroblasts (HFF) at
      concentrations that have been achieved in humans with no significant adverse
      effects. The concentrations of DFO required for 50 and 90% reduction in the
      production of a HCMV-late antigen ranged for several HCMV strains from 3.1 to 4.9
      microM and from 14.2 to 17.3 microM, respectively. DFO concentration of 60 microM
      had no significant effect on the viability of HFF cells. Inhibitory effects of
      DFO on HCMV replication were completely prevented by co-incubation with
      stoichiometric amounts of Fe3+.

PMID- 7811062
TI  - Cloning of an insecticidal cholesterol oxidase gene and its expression in
      bacteria and in plant protoplasts.
AB  - We cloned and sequenced structural gene choM, which encodes an insecticidally
      active cholesterol oxidase in Streptomyces sp. strain A19249. The primary
      translation product was predicted to be a 547-amino-acid protein whose first 43
      amino acids constitute a secretory signal peptide. Expression of the gene with
      the signal sequence in Escherichia coli resulted in production of a protein that
      had enzymatic and insecticidal properties which were indistinguishable from those
      of the cholesterol oxidase secreted by Streptomyces sp. strain A19249. Expression
      of the gene with or without the signal sequence in tobacco protoplasts resulted
      in production of an enzymatically active cholesterol oxidase.

PMID- 7811061
TI  - Use of the CAMP test for identification of Listeria monocytogenes.

PMID- 7811064
TI  - Detection of Salmonella typhimurium in dairy products with flow cytometry and
      monoclonal antibodies.
AB  - Flow cytometry, combined with fluorescently labelled monoclonal antibodies,
      offers advantages of speed and sensitivity for the detection of specific
      pathogenic bacteria in foods. We investigated the detection of Salmonella
      typhimurium in eggs and milk. Using a sample clearing procedure, we determined
      that the detection limit was on the order of 10(3) cells per ml after a total
      analysis time of 40 min. After 6 h of nonselective enrichment, the detection
      limits were 10 cells per ml for milk and 1 cell per ml for eggs, even in the
      presence of a 10,000-fold excess of Escherichia coli cells.

PMID- 7811063
TI  - High-efficiency transformation of Pichia stipitis based on its URA3 gene and a
      homologous autonomous replication sequence, ARS2.
AB  - This paper describes the first high-efficiency transformation system for the
      xylose-fermenting yeast Pichia stipitis. The system includes integrating and
      autonomously replicating plasmids based on the gene for orotidine-5'-phosphate
      decarboxylase (URA3) and an autonomous replicating sequence (ARS) element (ARS2)
      isolated from P. stipitis CBS 6054. Ura- auxotrophs were obtained by selecting
      for resistance to 5-fluoroorotic acid and were identified as ura3 mutants by
      transformation with P. stipitis URA3. P. stipitis URA3 was cloned by its homology
      to Saccharomyces cerevisiae URA3, with which it is 69% identical in the coding
      region. P. stipitis ARS elements were cloned functionally through plasmid rescue.
      These sequences confer autonomous replication when cloned into vectors bearing
      the P. stipitis URA3 gene. P. stipitis ARS2 has features similar to those of the
      consensus ARS of S. cerevisiae and other ARS elements. Circular plasmids bearing
      the P. stipitis URA3 gene with various amounts of flanking sequences produced 600
      to 8,600 Ura+ transformants per micrograms of DNA by electroporation. Most
      transformants obtained with circular vectors arose without integration of vector
      sequences. One vector yielded 5,200 to 12,500 Ura+ transformants per micrograms
      of DNA after it was linearized at various restriction enzyme sites within the P.
      stipitis URA3 insert. Transformants arising from linearized vectors produced
      stable integrants, and integration events were site specific for the genomic ura3
      in 20% of the transformants examined. Plasmids bearing the P. stipitis URA3 gene
      and ARS2 element produced more than 30,000 transformants per micrograms of
      plasmid DNA. Autonomously replicating plasmids were stable for at least 50
      generations in selection medium and were present at an average of 10 copies per
      nucleus.

PMID- 7811065
TI  - Reduction and mutagenic activation of nitroaromatic compounds by a Mycobacterium
      sp.
AB  - Mycobacterium sp. strain Pyr-1 cells, which were grown to the stationary phase in
      media with and without pyrene, were centrifuged and resuspended in a medium
      containing 1-nitropyrene. Cells that had been grown with pyrene oxidized up to
      20% of the added 1-nitropyrene to 1-nitropyrene-cis-9,10- and 4,5-dihydrodiols.
      However, cells that had been grown without pyrene reduced up to 70% of the 1
      nitropyrene to 1-aminopyrene but did not produce dihydrodiols. The nitroreductase
      activity was oxygen insensitive, intracellular, and inducible by nitro compounds.
      Nitroreductase activity was inhibited by p-chlorobenzoic acid, o-iodosobenzoic
      acid, menadione, dicumarol, and antimycin A. Extracts from cells that had been
      grown without pyrene activated 1-nitropyrene, 1-amino-7-nitrofluorene, 2,7
      dinitro-9-fluorenone, 1,3-dinitropyrene, 1,6-dinitropyrene, and 6-nitrochrysene
      to DNA-damaging products, as shown in Salmonella typhimurium tester strains by
      the reversion assay and by induction of the umuC gene. Activation of nitro
      compounds, as shown by the umu test, was enhanced by NADPH. This study shows that
      Mycobacterium sp. strain Pyr-1 metabolizes nitroaromatic compounds by both
      oxidative and reductive pathways. During reduction, it generates products that
      are mutagenic.

PMID- 7811066
TI  - Effect of growth phase and parental cell survival in river water on plasmid
      transfer between Escherichia coli strains.
AB  - We evaluated the transfer to and from Escherichia coli of endogenously isolated
      plasmid material from the River Butron during the growth of three donor strains
      and two recipient strains as well as after the survival of these parental cells
      in river water. Transfer frequency varied greatly during the growth of donor
      cells, with minimum values in the exponential phase; frequency remained constant,
      however, during the growth of recipient strains. After survival in river water,
      donor cells lost their ability for plasmid transfer before any other
      physiological variations in the cells caused by environmental stress were
      detected. Under the same conditions and during equal periods, however, no
      variation in the ability of recipient cells to receive and express plasmid
      material was observed.

PMID- 7811067
TI  - Cloning of Frankia species putative tRNA(Pro) genes and their efficacy for pSAM2
      site-specific integration in Streptomyces lividans.
AB  - pSAM2 is a conjugative Streptomyces ambofaciens mobile genetic element that can
      transfer and integrate site specifically in the genome. The chromosomal
      attachment site (attB) for pSAM2 site-specific recombination for two Frankia
      species was analyzed. It overlaps putative proline tRNA genes having a 3'
      terminal CCA sequence, an uncommon feature among actinomycetes. pSAM2 is able to
      integrate into a cloned Frankia attB site harbored in Streptomyces lividans. The
      integration event removes the 3'-terminal CCA sequence and introduces a single
      nucleotide difference in the T psi C loop of the putative Frankia tRNA(Pro) gene.
      Major differences between the attP sequence from pSAM2 and the Frankia attB
      sequence restrict the identity segment to a 43-bp-long region. Only one mismatch
      is found between these well-conserved att segments. This nucleotide substitution
      makes a BstBI recognition site in Frankia attB and was used to localize the
      recombination site in a 25-bp region going from the anticodon to the T psi C loop
      of the tRNA(Pro) sequence. Integration of pSAM2 into the Frankia attB site is the
      first step toward introduction of pSAM2 derivatives into Frankia spp.

PMID- 7811068
TI  - Biotransformations of Aroclor 1242 in Hudson River test tube microcosms.
AB  - A microcosm system to physically model the fate of Aroclor 1242 in Hudson River
      sediment was developed. In the dark at 22 to 25 degrees C with no amendments
      (nutrients, organisms, or mixing) and with overlying water being the only source
      of oxygen, the microcosms developed visibly distinct aerobic and anaerobic
      compartments in 2 to 4 weeks. Extensive polychlorinated biphenyl (PCB)
      biodegradation was observed in 140 days. Autoclaved controls were unchanged
      throughout the experiments. In the surface sediments of these microcosms, the
      PCBs were biologically altered by both aerobic biodegrading and reductive
      dechlorinating microorganisms, decreasing the total concentration from 64.8 to
      18.0 micromol/kg of sediment in 1140 days. This is the first laboratory
      demonstration of meta dechlorination plus aerobic biodegradation in stationary
      sediments. In contrast, the primary mechanism of microbiological attack on PCBs
      in aerobic subsurface sediments was reductive dechlorination. The concentration
      of PCBs remained constant at 64.8 micromol/kg of sediment, but the average number
      of chlorines per biphenyl decreased from 3.11 to 1.84 in 140 days. The
      selectivities of microorganisms in these sediments were characterized by meta and
      para dechlorination. Our results provide persuasive evidence that naturally
      occurring microorganisms in the Hudson River have the potential to attack the
      PCBs from Aroclor 1242 releases both aerobically and anaerobically at rapid
      rates. These unamended microcosms represent a unique method for determining the
      fate of released PCBs in river sediments.

PMID- 7811069
TI  - Mineralization of the herbicide atrazine as a carbon source by a Pseudomonas
      strain.
AB  - Strain YAYA6 was isolated from a mixed microbial community that was growing on
      atrazine as a sole carbon source and formed quantitative amounts of chloride and
      nitrate. This strain was identified as a member of the true pseudomonad group
      (RNA group I) and was given the designation DMS 93-99. The growth yield when
      atrazine was the sole carbon and nitrogen source was 80 g (dry weight) of cells
      per mol of atrazine, and the cell doubling time was around 11 h. Approximately
      20% of [U-ring 14C]atrazine was mineralized during primary degradation of
      atrazine. After atrazine disappeared from the culture supernatant, mineralization
      continued until the level of mineralization was more than 50%. Under different
      experimental conditions 10% of the atrazine supplied initially was converted to
      cyanuric acid and < 1% was converted to other s-triazines after prolonged
      incubation. Degradation proceeded via dechlorination and N-dealkylation. Atrazine
      was degraded until the concentration was circa 0.1 milligrams/liter. We obtained
      evidence showing that strain YAYA6 has specific uptake mechanisms for atrazine
      but less specific degradation mechanisms for s-triazines.

PMID- 7811070
TI  - Homologous expression of recombinant manganese peroxidase in Phanerochaete
      chrysosporium.
AB  - The promoter region of the glyceraldehyde-3-phosphate dehydrogenase gene (gpd)
      was used to drive expression of mnp1, the gene encoding Mn peroxidase isozyme 1,
      in primary metabolic cultures of Phanerochaete chrysosporium. A 1,100-bp fragment
      of the P. chrysosporium gpd promoter region was fused upstream of the mnp1 gene
      to construct plasmid pAGM1, which contained the Schizophyllum commune ade5 gene
      as a selectable marker. pAGM1 was used to transform a P. chrysosporium ade1
      auxotroph to prototrophy. Ade+ transformants were screened for peroxidase
      activity on a solid medium containing high carbon and high nitrogen (2% glucose
      and 24 mM NH4 tartrate) and o-anisidine as the peroxidase substrate. Several
      transformants that expressed high peroxidase activities were purified and
      analyzed further in liquid cultures. Recombinant Mn peroxidase (rMnP) was
      expressed and secreted by transformant cultures on day 2 under primary metabolic
      growth conditions (high carbon and high nitrogen), whereas endogenous wild-type
      mnp genes were not expressed under these conditions. Expression of rMnP was not
      influenced by the level of Mn in the culture medium, as previously observed for
      the wild-type Mn peroxidase (wtMnP). The amount of active rMnP expressed and
      secreted in this system was comparable to the amount of enzyme expressed by the
      wild-type strain under ligninolytic conditions. rMnP was purified to homogeneity
      by using DEAE-Sepharose chromatography, Blue Agarose chromatography, and Mono Q
      column chromatography. The M(r) and absorption spectrum of rMnP were essentially
      identical to the M(r) and absorption spectrum of wtMnP, indicating that heme
      insertion, folding, and secretion were normal.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7811071
TI  - Optimization of an Escherichia coli formate dehydrogenase assay for selenium
      compounds.
AB  - A microbiological assay to detect different chemical compounds of selenium for
      potential future use in the study of the distribution of these chemical forms in
      foods is being developed. This assay is based on the detection, by infrared
      analysis, of CO2 in a culture of Escherichia coli when the bacteria are grown in
      the presence of various selenium compounds. The CO2 production is the result of
      selenium-dependent formate dehydrogenase activity, which catalyzes oxidation of
      formic acid produced during glucose metabolism. Smooth response curves were
      generated over several orders of magnitude for selenocystine, selenite, and
      selenomethionine. The assay detects selenium concentrations (above background) as
      low as 1.5 nM for selenocystine and selenite and 4 nM for selenomethionine in
      minimal medium. Detection of selenomethionine was enhanced (to a sensitivity of
      1.5 nM) by the addition of methionine to minimal medium and was enhanced even
      further (to a sensitivity of 0.8 nM) by the addition of a defined mixture of
      amino acids. Selenomethionine could be assayed in the presence of an amino acid
      concentration which is proportional to the amino acid/elemental selenium ratio
      found in a wheat gluten reference material (NIST SRM 8418). This implies that the
      assay can detect selenium compounds in a variety of foods at low concentrations,
      avoiding the background CO2 production caused by high concentrations of non
      selenium-containing amino acids. The observation that methionine enhanced
      selenomethionine availability for formate dehydrogenase synthesis supports
      studies in animals demonstrating that methionine controls selenomethionine
      incorporation into selenoenzymes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7811072
TI  - PCR primers that allow intergeneric differentiation of ascomycetes and their
      application to Verticillium spp.
AB  - A pair of conserved PCR primers, designated NMS1 and NMS2, that amplify a region
      in the mitochondrial small rRNA gene region were designed for fungi belonging to
      the class Ascomycetes. These primers were tested with members of eight fungal
      genera (Aspergillus, Fusarium, Magnaporthe, Mycospharella, Neurospora,
      Saccharomyces, Sclerotinia, Verticillium) and 10 Verticillium species
      (Verticillium albo-atrum, Verticillium chlamydosporium, Verticillium cinnebarium,
      Verticillium dahliae, Verticillium fungicola, Verticillium lecanii, Verticillium
      lateritium, Verticillium nigrescens, Verticillium psaliotae, and Verticillium
      tricorpus). The primers were also tested with 35 isolates of V. dahliae obtained
      from diverse geographic areas and diverse hosts. The results of a restriction
      fragment length polymorphism analysis of the region amplified by the primers
      differentiated the genera examined and the results of a DNA sequence analysis of
      the amplified region differentiated the Verticillium species. Two Fusarium
      species were also differentiated by the results of the restriction fragment
      length polymorphism analysis. On the basis of the nucleotide sequences of the
      amplified regions, we obtained a pair of PCR primers that could be used to
      differentiate V. dahliae from the other fungal isolates tested, including V. albo
      atrum, a closely related plant-pathogenic species. The V. dahliae-specific PCR
      primer may aid in more rapid and specific detection of the pathogen directly in
      plant and/or soil samples. PCR primers NMS1 and NMS2 may be used as potential
      mitochondrial markers for studying fungal cytoplasmic inheritance of ascomycetes
      and for identifying DNA probes that are informative at or below the genus level.

PMID- 7811073
TI  - Construction of an expression system for engineering of the lantibiotic Pep5.
AB  - Pep5 is a lanthionine-containing antimicrobial peptide which is produced by
      Staphylococcus epidermidis 5. Its structural gene, pepA, is located on the 20-kb
      plasmid pED503. A 6.2-kb fragment of pED503 containing pepA, the immunity gene
      pepI, and 5.4 kb of downstream sequence was able to direct biosynthesis of
      biologically active Pep5 in a nonproducing variant of the producer strain which
      is devoid of pED503. In addition to producing wild-type Pep5 with a molecular
      mass of 3,488 Da, the clone produced a peptide with an eightfold-lower
      bactericidal activity and a mass of 3,506 Da, indicative of incomplete
      dehydration of one hydroxyamino acid. For construction of the expression system,
      this 6.2-kb fragment was cut into a 1.39-kb fragment containing pepA and pepI and
      a 4.8-kb fragment covering the remaining downstream region. This 4.8-kb fragment
      was directly cloned into an Escherichia coli-Staphylococcus shuttle vector,
      yielding a new plasmid (pGB9) into which mutated pepA genes generated on the 1.39
      kb fragment can be reinserted to yield a functional Pep5 biosynthesis gene
      cluster. To test the expression system, two mutants were constructed. Lys-18-Pro
      Pep5 was produced in its dehydrated form and a partially hydrated form in amounts
      comparable to those of the wild-type peptide. In contrast, only small amounts of
      Phe-23-Asp Pep5 were excreted, indicating that some residues in the propeptide
      part of the prelantibiotic may be crucial for certain steps in the biosynthetic
      pathway of lantibiotics.

PMID- 7811074
TI  - Direct measurement of chlorine penetration into biofilms during disinfection.
AB  - Transient chlorine concentration profiles were measured in biofilms during
      disinfection by use of a microelectrode developed for this investigation. The
      electrode had a tip diameter of ca. 10 microm and was sensitive to chlorine in
      the micromolar range. The biofilms contained Pseudomonas aeruginosa and
      Klebsiella pneumoniae. Chlorine concentrations measured in biofilms were
      typically only 20% or less of the concentration in the bulk liquid. Complete
      equilibration with the bulk liquid did not occur during the incubation time of 1
      to 2 h. The penetration depth of chlorine into the biofilm and rate of
      penetration varied depending on the measurement location, reflecting
      heterogeneity in the distribution of biomass and in local hydrodynamics. The
      shape of the chlorine profiles, the long equilibration times, and the dependence
      on the bulk chlorine concentration showed that the penetration was a function of
      simultaneous reaction and diffusion of chlorine in the biofilm matrix. Frozen
      cross sections of biofilms, stained with a redox dye and a DNA stain, showed that
      the area of chlorine penetration overlapped with nonrespiring zones near the
      biofilm-bulk fluid interface. These data indicate that the limited penetration of
      chlorine into the biofilm matrix is likely to be an important factor influencing
      the reduced efficacy of this biocide against biofilms as compared with its action
      against planktonic cells.

PMID- 7811075
TI  - Flow cytometric analysis of the cellular DNA content of Salmonella typhimurium
      and Alteromonas haloplanktis during starvation and recovery in seawater.
AB  - Flow cytometry was used to investigate the heterogeneity of the DNA content of
      Salmonella typhimurium and Alteromonas haloplanktis cells that were starved and
      allowed to recover in seawater. Hoechst 33342 (bisbenzimide) was used as a DNA
      specific dye to discriminate between DNA subpopulations. The DNA contents of both
      strains were heterogeneous during starvation. S. typhimurium cells contained one
      or two genomes, and A. haloplanktis cells contained up to six genomes. S.
      typhimurium genomes were fully replicated at the onset of starvation. Each
      replication cycle was completed in the early stage of starvation for A.
      haloplanktis by stopping cells in the partition step of the cell cycle prior to
      division. Multigenomic marine cells can undergo rapid cell division without DNA
      synthesis upon recovery, resulting in large fluctuations in the DNA contents of
      individual cells. In contrast, the heterogeneity of the DNA distribution of S.
      typhimurium cells was preserved during recovery. The fluctuations in the DNA
      fluorescence of this strain seem to be due to topological changes in DNA. Flow
      cytometry may provide a new approach to understanding dynamic and physiological
      changes in bacteria by detecting cellular heterogeneity in response to different
      growth conditions.

PMID- 7811076
TI  - Parallel formation and synergism of hydrolytic enzymes and peptaibol antibiotics,
      molecular mechanisms involved in the antagonistic action of Trichoderma harzianum
      against phytopathogenic fungi.
AB  - Chitinase, beta-1,3-glucanase, and protease activities were formed when
      Trichoderma harzianum mycelia, grown on glucose as the sole carbon source, were
      transferred to fresh medium containing cell walls of Botrytis cinerea.
      Chitobiohydrolase, endochitinase, and beta-1,3-glucanase activities were
      immunologically detected in culture supernatants by Western blotting
      (immunoblotting), and the first two were quantified by enzyme-linked
      immunosorbent assay. Under the same conditions, exogenously added [U-14C]valine
      was incorporated in acetone-soluble compounds with an apparent M(r) of < 2,000.
      These compounds comigrated with the peptaibols trichorzianines A1 and B1 in thin
      layer chromatography and released [U-14C]valine after incubation in 6N HCl.
      Incorporation of radioactive valine into this material was stimulated by the
      exogenous supply of alpha-aminoisobutyric acid, a rare amino acid which is a
      major constituent of peptaibols. The obtained culture supernatants inhibited
      spore germination as well as hyphal elongation of B. cinerea. Culture
      supernatants from mycelia placed in fresh medium without cell walls of B. cinerea
      did not show hydrolase activities, incorporation of [U-14C]valine into peptaibol
      like compounds, and inhibition of fungal growth. Purified trichorzianines A1 and
      B1 as well as purified chitobiohydrolase, endochitinase, or beta-1,3-glucanase
      inhibited spore germination and hyphal elongation, but at concentrations higher
      than those observed in the culture supernatants. However, when the enzymes and
      the peptaibols were tested together, an antifungal synergistic interaction was
      observed and the 50% effective dose values obtained were in the range of those
      determined in the culture supernatants. Therefore, the parallel formation and
      synergism of hydrolytic enzymes and antibiotics may have an important role in the
      antagonistic action of T. harzianum against fungal phytopathogens.

PMID- 7811077
TI  - Molecular characterization of Yersinia enterocolitica by pulsed-field gel
      electrophoresis and hybridization of DNA fragments to ail and pYV probes.
AB  - Sixty strains of Yersinia enterocolitica from five serogroups (O:3; O:9; O:8;
      O:5; and O:5,27) and eight non-Y. enterocolitica strains, recovered from diverse
      sources (humans, animals, food, and the environment) in Europe, Argentina, and
      the United States, were examined by the pulsed-field gel electrophoresis (PFGE)
      technique of contour clamped homogeneous electric field electrophoresis (CHEF) by
      using NotI and XbaI as restriction enzymes. NotI and XbaI generated 36 and 33
      restriction endonuclease digestion profiles (REDP), respectively. By combining
      the results of both enzymes, 42 unique genomic groups were differentiated. DNA
      fragments were transferred to nylon membranes and hybridized with digoxigenin
      labelled oligonucleotide probes to the ail gene and virulence plasmid to
      determine hybridization patterns and the potential virulence of the strains. The
      strains were tested for the presence of the plasmid by PFGE-CHEF and phenotypic
      characteristics encoded for by the virulence plasmid. Thirty of the 60 Y.
      enterocolitica strains tested harbored the virulence plasmid. The specificity of
      the ail and pYV probes was 100% when tested with 68 Yersinia strains and 19
      different non-Yersinia strains. Sixteen selected Y. enterocolitica strains were
      tested for their virulence by lethality in iron- and desferrioxamine-sensitized
      mice. No correlation between REDP and the virulence of the strains was observed.
      The observed REDP and the hybridization patterns were very homogeneous within a
      serogroup and independent of the source of isolation. In addition, PFGE-CHEF was
      shown to be valuable in identifying and confirming serogroups. Principal
      component analysis of Dice similarity indices from REDP was an excellent tool for
      determining genetic relatedness among strains.

PMID- 7811078
TI  - Sambutoxin, a new mycotoxin produced by toxic Fusarium isolates obtained from
      rotted potato tubers.
AB  - Ninety-nine isolates of Fusarium species were obtained from rotted potato tubers
      from various parts of Korea. Of these isolates, 80 were identified as Fusarium
      oxysporum, F. solani, or F. sambucinum. The isolates of these species were grown
      on autoclaved wheat grains and examined for toxicity in a rat-feeding test. A
      total of 8 of 57 F. oxysporum isolates, 3 of 14 F. solani isolates, and 5 of 9 F.
      sambucinum isolates caused the death of the rats. Of the 16 toxic isolates, 1
      isolate of F. oxysporum produced a substantial amount of moniliformin, which
      could account for its toxicity. None of the other 15 isolates produced
      trichothecenes, moniliformin, fusarochromanone, fumonisin B1, or wortmannin. F.
      sambucinum PZF-4 produced an unknown toxin in wheat culture. This new toxin,
      given the trivial name sambutoxin, caused toxic effects in rats, including body
      weight loss, feed refusal, hemorrhage in the stomach and intestines, and,
      finally, death when rats were fed diets supplemented with 0.05 and 0.1%
      sambutoxin. The toxin was also toxic to chicken embryos, and the 50% lethal
      concentration was 29.6 micrograms per egg. Sambutoxin formed as white crystals
      that turned purple when combined with reagents such as sulfuric acid and p
      anisaldehyde. It exhibited a green color immediately after treatment with
      potassium ferricyanide-ferric chloride. Its UV spectrum had absorption maxima at
      213, 233, and 254 nm, and its infrared spectrum showed an amide group at 1,650
      and 1,560 cm-1 and a hydroxy group at 3,185 cm-1. Mass spectrometry showed that
      the molecular weight of the toxin was 453 and the molecular formula was
      C28H39NO4.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7811079
TI  - Isolation, characterization, and analysis of the expression of the cbhII gene of
      Phanerochaete chrysosporium.
AB  - Two cDNA sequences representing putative allelic variants of the Phanerochaete
      chrysosporium cbhII gene were isolated by hybridization to the Trichoderma reesei
      cbhII gene. Both of the equivalent genomic sequences were subsequently isolated
      by the inverse PCR technique. DNA sequencing showed that the cbhII open reading
      frame of 1,380 bp codes for a putative polypeptide of 460 amino acids which is
      interrupted by six introns. The domain structure found in T. reesei cbhII is
      conserved in the equivalent P. chrysosporium protein. The overall similarity
      between the two gene products is 54%, with the region of highest conservation
      being found in the cellulose-binding domain (65%). Unlike the cbhI gene of P.
      chrysosporium, cbhII does not appear to be a member of a class of closely related
      genes. CBHII is a new member of family B of the beta-1, 4-glucanases. Alignment
      of the P. chrysosporium and T. reesei CBHII protein sequences showed that all of
      the residues important for the formation of the extended loops of the catalytic
      domain and those residues that are involved in the catalytic action of the T.
      reesei enzyme are also present in the P. chrysosporium equivalent. The profiles
      of cbh gene expression in P. chrysosporium reveal that while cbhI.1 and cbhI.2
      could be coregulated, cbhII can be independently controlled. The latter is so far
      the only cellulase gene found to be expressed when the fungus is grown on oat
      spelt arabinoxylan, suggesting that it may play an active role in the xylanolytic
      as well as the cellulolytic systems.

PMID- 7811080
TI  - Zwittermicin A-producing strains of Bacillus cereus from diverse soils.
AB  - Bacillus cereus UW85 produces a novel aminopolyol antibiotic, zwittermicin A,
      that contributes to the ability of UW85 to suppress damping-off of alfalfa caused
      by Phytophthora medicaginis. UW85 produces a second antibiotic, provisionally
      designated antibiotic B, which also contributes to suppression of damping-off but
      has not been structurally defined yet and is less potent than zwittermicin A. The
      purpose of this study was to isolate genetically diverse strains of B. cereus
      that produce zwittermicin A and suppress disease. We found that most isolates of
      B. cereus that were sensitive to phage P7 or inhibited the growth of Erwinia
      herbicola produced zwittermicin A; therefore, phage typing and E. herbicola
      inhibition provided indirect, but rapid screening tests for identification of
      zwittermicin A-producing isolates. We used these tests to screen a collection of
      4,307 B. cereus and Bacillus thuringiensis isolates obtained from bacterial stock
      collections and from diverse soils collected in Honduras, Panama, Australia, The
      Netherlands, and the United States. A subset of the isolates screened by the P7
      sensitivity and E. herbicola inhibition tests were assayed directly for
      production of zwittermicin A, leading to the identification of 57 isolates that
      produced zwittermicin A; 41 of these isolates also produced antibiotic B. Eight
      isolates produced antibiotic B but not zwittermicin A. The assay for phage P7
      sensitivity was particularly useful because of its simplicity and rapidity and
      because 22 of the 23 P7-sensitive isolates tested produced zwittermicin A.
      However, not all zwittermicin A-producing isolates were sensitive to P7, and the
      more labor-intensive E. herbicola inhibition assay identified a larger proportion
      of the zwittermicin A producers.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7811081
TI  - Genetic analysis of regions of the Lactococcus lactis subsp. lactis plasmid pRS01
      involved in conjugative transfer.
AB  - The genes responsible for conjugative transfer of the 48.4-kb Lactococcus lactis
      subsp. lactis ML3 plasmid pRS01 were localized by insertional mutagenesis.
      Integration of the IS946-containing plasmid pTRK28 into pRS01 generated a pool of
      stable cointegrates, including a number of plasmids altered in conjugative
      proficiency. Mapping of pTRK28 insertions and phenotypic analysis of cointegrate
      plasmids identified four distinct regions (Tra1, Tra2, Tra3, and Tra4) involved
      in pRS01 conjugative transfer. Tra3 corresponds closely to a region previously
      identified (D. G. Anderson and L. L. McKay, J. Bacteriol. 158:954-962, 1984).
      Another region (Tra4) was localized within an inversion sequence shown to
      correlate with a cell aggregation phenotype. Tra1 and Tra2, two previously
      unidentified regions, were located at a distance of 9 kb from Tra3. When provided
      in trans, a cloned portion of the Tra3 region complemented Tra3 mutants.

PMID- 7811082
TI  - Genetic and plasmid diversity within natural populations of Pseudomonas syringae
      with various exposures to copper and streptomycin bactericides.
AB  - We examined the genetic and plasmid diversity within natural populations of
      Pseudomonas syringae isolated from three ornamental pear nurseries in eastern
      Oklahoma. The bactericide spray regimen differed at each nursery; copper and
      streptomycin, only copper, and no bactericides were applied at nurseries I, II,
      and III respectively. Resistance to copper (Cur) and resistance to streptomycin
      (Smr) were determined for 1,938 isolates of P. syringae; isolates from nurseries
      I and II were generally Cur Sms; whereas most isolates from nursery III were Cus
      Sms. The plasmid profiles of 362 isolates were determined, and six, one, seven,
      and four plasmid profiles were obtained for Cur, Smr, Cur Smr, and Cus Sms
      isolates, respectively. All Smr plasmids contained sequences homologous to the
      strA and strB Smr genes from broad-host-range plasmid RSF1010 and were associated
      with Smr transposon Tn5393. Plasmids were placed into two groups on the basis of
      hybridization to the oriV and par sequences from pOSU900, a cryptic plasmid in P.
      syringae pv. syringae. A total of 100 randomly chosen P. syringae isolates from
      nurseries I and III were analyzed for genetic diversity by using the arbitrarily
      primed PCR (AP-PCR) technique. An analysis of chromosomal genotypes by AP-PCR
      revealed a high degree of genetic diversity among the isolates, and the results
      of this analysis indicated that the isolates could be clustered into two distinct
      groups. The plasmid profiles were specific to isolates belonging to particular AP
      PCR groups. Within each AP-PCR group, identical plasmid profiles were produced by
      isolates that had different chromosomal genotypes, implying that plasmid transfer
      has played an important role in the dissemination of Cur and Smr within the
      populations studied.

PMID- 7811083
TI  - A reporter gene analysis of penicillin biosynthesis gene expression in
      Penicillium chrysogenum and its regulation by nitrogen and glucose catabolite
      repression.
AB  - Vectors which possess a truncated niaD gene encoding nitrate reductase were
      developed to allow targeted gene integration during transformation of an niaD
      mutant Penicillium chrysogenum host. The Penicillium genes pcbC and penAB are
      immediately adjacent to each other and are divergently transcribed, with an
      intergenic control region serving as their promoters. Gene fusions were
      constructed with a reporter gene, uidA, which encodes beta-glucuronidase. The
      pcbC-penAB intergenic region was fused to the uidA gene in both orientations so
      that regulated expression of each structural gene could be investigated. These
      fusion genes were targeted to the chromosomal site of the niaD locus of P.
      chrysogenum, and their expression was examined under different growth conditions.
      The expression of each of these penicillin biosynthesis genes was found to be
      regulated by nitrogen repression, glucose repression, and growth stage control.

PMID- 7811084
TI  - Adaptation of Pseudomonas putida S12 to ethanol and toluene at the level of fatty
      acid composition of membranes.
AB  - Pseudomonas putida S12 was more tolerant to ethanol when preadapted to
      supersaturating concentrations of toluene. Cellular reactions at the membrane
      level to the toxicities of both compounds were different. In growing cells of P.
      putida S12, sublethal concentrations of toluene resulted in an increase in the
      degree of saturation of the membrane fatty acids, whereas toxically equivalent
      concentrations of ethanol led to a decrease in this value. Contrary to this,
      cells also reacted to both substances with a strong increase of the trans
      unsaturated fatty acids and a corresponding decrease of the cis unsaturated fatty
      acids under conditions where growth and other cellular membrane reactions were
      totally inhibited. While the isomerization of cis to trans unsaturated fatty
      acids compensates for the fluidizing effect caused by ethanol, a decrease in the
      degree of saturation is antagonistic with respect to the chemo-physical
      properties of the membrane. Consequently, the results support the hypothesis that
      the decrease in the degree of saturation induced by ethanol is not an adaptation
      mechanism but is caused by an inhibitory effect of the compound on the
      biosynthesis of saturated fatty acids.

PMID- 7811086
TI  - Preferential degradation of phenolic lignin units by two white rot fungi.
AB  - The differential biodegradation of phenolic and nonphenolic (C-4-etherified)
      lignin units in wheat straw treated with the white rot fungi Pleurotus eryngii
      and Phanerochaete chrysosporium was investigated under solid-state fermentation
      conditions. Two analytical techniques applied to permethylated straw were used
      for this purpose, i.e., alkaline CuO degradation and analytical pyrolysis (both
      followed by gas chromatography-mass spectrometry for product identification).
      Despite differences in the enzymatic machinery produced, both ligninolytic fungi
      caused a significant decrease in the relative amount of phenolic lignin units
      during the degradation process. Nevertheless, no differences in the
      biodegradation rates of phenolic and etherified cinnamic acids were observed.
      Changes in lignin composition and cinnamic acid content were also analyzed in the
      phenolic and nonphenolic lignin moieties. The results obtained are discussed in
      the context of the enzymatic mechanisms of lignin biodegradation.

PMID- 7811085
TI  - Factors involved in adherence of lactobacilli to human Caco-2 cells.
AB  - A quantitative assay performed with bacterial cells labelled with [3H]thymidine
      was used to investigate factors involved in the adherence of human isolates
      Lactobacillus acidophilus BG2FO4 and NCFM/N2 and Lactobacillus gasseri ADH to
      human Caco-2 intestinal cells. For all three strains, adherence was concentration
      dependent, greater at acidic pH values, and significantly greater than adherence
      of a control dairy isolate, Lactobacillus delbrueckii subsp. bulgaricus 1489.
      Adherence of L. acidophilus BG2FO4 and NCFM/N2 was decreased by protease
      treatment of the bacterial cells, whereas adherence of L. gasseri ADH either was
      not affected or was enhanced by protease treatment. Putative surface layer
      proteins were identified on L. acidophilus BG2FO4 and NCFM/N2 cells but were not
      involved in adherence. Periodate oxidation of bacterial cell surface
      carbohydrates significantly reduced adherence of L. gasseri ADH, moderately
      reduced adherence of L. acidophilus BG2FO4, and had no effect on adherence of L.
      acidophilus NCFM/N2. These results indicate that Lactobacillus species adhere to
      human intestinal cells via mechanisms which involve different combinations of
      carbohydrate and protein factors on the bacterial cell surface. The involvement
      of a secreted bridging protein, which has been proposed as the primary mediator
      of adherence of L. acidophilus BG2FO4 in spent culture supernatant (M.-H.
      Coconnier, T. R. Klaenhammer, S. Kerneis, M.-F. Bernet, and A. L. Servin, Appl.
      Environ. Microbiol. 58:2034-2039, 1992), was not confirmed in this study. Rather,
      a pH effect on Caco-2 cells contributed significantly to the adherence of this
      strain in spent culture supernatant.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7811087
TI  - Anaerobic oxidation of ferrous iron by purple bacteria, a new type of
      phototrophic metabolism.
AB  - Anoxic iron-rich sediment samples that had been stored in the light showed
      development of brown, rusty patches. Subcultures in defined mineral media with
      ferrous iron (10 mmol/liter, mostly precipitated as FeCO3) yielded enrichments of
      anoxygenic phototrophic bacteria which used ferrous iron as the sole electron
      donor for photosynthesis. Two different types of purple bacteria, represented by
      strains L7 and SW2, were isolated which oxidized colorless ferrous iron under
      anoxic conditions in the light to brown ferric iron. Strain L7 had rod-shaped,
      nonmotile cells (1.3 by 2 to 3 microns) which frequently formed gas vesicles. In
      addition to ferrous iron, strain L7 used H2 + CO2, acetate, pyruvate, and glucose
      as substrate for phototrophic growth. Strain SW2 had small rod-shaped, nonmotile
      cells (0.5 by 1 to 1.5 microns). Besides ferrous iron, strain SW2 utilized H2 +
      CO2, monocarboxylic acids, glucose, and fructose. Neither strain utilized free
      sulfide; however, both strains grew on black ferrous sulfide (FeS) which was
      converted to ferric iron and sulfate. Strains L7 and SW2 grown
      photoheterotrophically without ferrous iron were purple to brownish red and
      yellowish brown, respectively; absorption spectra revealed peaks characteristic
      of bacteriochlorophyll a. The closest phototrophic relatives of strains L7 and
      SW2 so far examined on the basis of 16S rRNA sequences were species of the genera
      Chromatium (gamma subclass of proteobacteria) and Rhodobacter (alpha subclass),
      respectively. In mineral medium, the new isolates formed 7.6 g of cell dry mass
      per mol of Fe(II) oxidized, which is in good agreement with a photoautotrophic
      utilization of ferrous iron as electron donor for CO2 fixation. Dependence of
      ferrous iron oxidation on light and CO2 was also demonstrated in dense cell
      suspensions. In media containing both ferrous iron and an organic substrate
      (e.g., acetate, glucose), strain L7 utilized ferrous iron and the organic
      compound simultaneously; in contrast, strain SW2 started to oxidize ferrous iron
      only after consumption of the organic electron donor. Ferrous iron oxidation by
      anoxygenic phototrophs is understandable in terms of energetics. In contrast to
      the Fe3+/Fe2+ pair (E0 = +0.77 V) existing in acidic solutions, the relevant
      redox pair at pH 7 in bicarbonate-containing environments, Fe(OH)3 + HCO3-/FeCO3,
      has an E0' of +0.2 V. Ferrous iron at pH 7 can therefore donate electrons to the
      photosystem of anoxygenic phototrophs, which in purple bacteria has a midpoint
      potential around +0.45 V. The existence of ferrous iron-oxidizing anoxygenic
      phototrophs may offer an explanation for the deposition of early banded-iron
      formations in an assumed anoxic biosphere in Archean times.

PMID- 7811088
TI  - Degradation of 1,4-dioxane by an actinomycete in pure culture.
AB  - An actinomycete capable of sustained aerobic growth on 1,4-dioxane was isolated
      from a dioxane-contaminated sludge samples. The actinomycete, CB1190, grows on
      1,4-dioxane as the sole carbon and energy source with a generation time of
      approximately 30 h. CB1190 degrades 1,4-dioxane at a rate of 0.33 mg of dioxane
      min-1 mg of protein-1 and mineralizes 59.5% of the dioxane to CO2. CB1190 also
      grows with other cyclic and linear ethers as the sole carbon and energy sources,
      including 1,3-dioxane, 2-methyl-1,3-dioxolane, tetrahydrofuran, tetrahydropyran,
      diethyl ether, and butyl methyl ether. CB1190 is capable of aerobic autotrophic
      growth on H2 and CO2.

PMID- 7811089
TI  - Detection and classification of Streptococcus thermophilus bacteriophages
      isolated from industrial milk fermentation.
AB  - In the last 30 years, 81 Streptococcus thermophilus bacteriophage isolates were
      collected from industrial yogurt (n = 40) and cheese (n = 41) fermentation. Forty
      six distinct restriction patterns of phage DNA (11 in yogurt and 35 in cheese)
      were observed. The phages were investigated for host range, serological
      properties, and DNA homology to study whether these three independent techniques
      can be used to classify the phages into taxonomic groups. Yogurt factory-derived
      phages were classified into the same two subgroups by serology, host range
      analysis, and hybridization with subgroup-specific DNA sequences. Cheese factory
      derived phages, however, could not be classified: the 35 cheese phage isolates
      with distinct restriction patterns showed 34 different host ranges. All but one
      cheese phage isolate showed serological cross-reactivity with yogurt phages. A
      phage DNA fragment that hybridized with all phage DNA samples was cloned,
      establishing the genetic relatedness of all S. thermophilus phages from our
      collection. With the sequence information from an unusually conserved S.
      thermophilus phage DNA element (H. Brussow, A. Probst, M. Fremont, and J. Sidoti,
      Virology 200:854-857, 1994), a PCR-based phage detection method was developed for
      cheese whey from a factory that produced mozzarella cheese with complex undefined
      starter mixes. PCR allowed the detection of phages in cheese whey (detection
      limit, 10(3) PFU/ml) which could not be detected by dot blot hybridization
      techniques (detection limit, 10(7) PFU/ml).

PMID- 7811090
TI  - Characterization of a psychrotrophic Arthrobacter gene and its cold-active beta
      galactosidase.
AB  - Enzymes with high specific activities at low temperatures have potential uses for
      chemical conversions when low temperatures are required, as in the food industry.
      Psychrotrophic microorganisms which grow at low temperatures may be a valuable
      source of cold-active enzymes that have higher activities at low temperatures
      than enzymes found for mesophilic microorganisms. To find cold-active beta
      galactosidases, we isolated and characterized several psychrotrophic
      microorganisms. One isolate, B7, is an Arthrobacter strain which produces beta
      galactosidase when grown in lactose minimal media. Extracts have a specific
      activity at 30 degrees C of 2 U/mg with o-nitrophenyl-beta-D-galactopyranoside as
      a substrate. Two isozymes were detected when extracts were subjected to
      electrophoresis in a nondenaturing polyacrylamide gel and stained for activity
      with 5-bromo-4-chloro-indolyl-beta-D-galactopyranoside (X-Gal). When chromosomal
      DNA was prepared and transformed into Escherichia coli, three different genes
      encoding beta-galactosidase activity were obtained. We have subcloned and
      sequenced one of these beta-galactosidase genes from the Arthrobacter isolate B7.
      On the basis of amino acid sequence alignment, the gene was found to have
      probable catalytic sites homologous to those from the E. coli lacZ gene. The gene
      encoded a protein of 1,016 amino acids with a predicted molecular mass of 111
      kDa. The enzyme was purified and characterized. The beta-galactosidase from
      isolate B7 has kinetic properties similar to those of the E. coli lacZ beta
      galactosidase but has a temperature optimum 20 degrees C lower than that of the
      E. coli enzyme.

PMID- 7811091
TI  - Ability of laboratory methods to predict in-use efficacy of antimicrobial
      preservatives in an experimental cosmetic.
AB  - The abilities of nine antimicrobial systems to preserve an experimental water
      based cosmetic formulation were evaluated by six microbiological challenge tests:
      the U.S. Pharmacopeia test; the British Pharmacopeia test; the Cosmetic,
      Toiletry, and Fragrance Association test; the rapid screen test; the sequential
      challenge test; and the post-use test. The antimicrobial systems contained
      various combinations and amounts of two parabens and a quaternary compound in
      order to provide a broad range of preservation. The results obtained were
      compared with the abilities of the formulations to support maintenance and growth
      of microorganisms in microfloras obtained from human axilla areas and finger skin
      during an 8-week simulated in-use test. Without statistical analysis all of the
      tests predicted the results obtained with well-preserved or poorly preserved
      formulations. The rapid screen test was the best test for predicting differences
      at intermediate levels of preservation. Statistically, all of the tests were
      equivalent predictors of preservation efficacy in the in-use test (P = 0.05). At
      the P = 0.10 level, only the U.S. Pharmacopeia, British Pharmacopeia, rapid
      screen, Cosmetic, Toiletry, and Fragrance Association tests were significantly
      predictive. The results of prediction by a test, based on the preservative levels
      used, agreed well with the in-use test results (P = 0.01). A total of 20% of the
      formulations that contained excessive microbial levels contained human axilla
      microorganisms. The levels of preservation in failed products were similar to the
      levels of preservation in unused controls.

PMID- 7811092
TI  - Purification and characterization of a thermostable thiol protease from a newly
      isolated hyperthermophilic Pyrococcus sp.
AB  - A hyperthermophilic archaeon strain, KOD1, was isolated from a solfatara at a
      wharf on Kodakara Island, Kagoshima, Japan. The growth temperature of the strain
      ranged from 65 to 100 degrees C, and the optimal temperature was 95 degrees C.
      The anaerobic strain was an S0-dependent heterotroph. Cells were irregular cocci
      and were highly motile with several polar flagella. The membrane lipid was of the
      ether type, and the GC content of the DNA was estimated to be 38 mol%. The 16S
      rRNA sequence was 95% homologous to that of Pyrococcus abyssi. The optimum growth
      pH and NaCl concentration of the strain KOD1 were 7.0 and 3%, respectively.
      Therefore, strain KOD1 was identified as a Pyrococcus sp. Strain KOD1 produced at
      least three extracellular proteases. One of the most thermostable proteases was
      purified 21-fold, and the molecular size was determined to be 44 kDa by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis and 45 kDa by gel filtration
      chromatography. The specific activity of the purified protease was 2,160 U/mg of
      protein. The enzyme exhibited its maximum activity at approximately pH 7.0 and at
      a temperature of 110 degrees with azocasein as a substrate. The enzyme activity
      was completely retained after heat treatment at 90 degrees C for 2 h, and the
      half-life of enzymatic activity at 100 degrees C was 60 min. The proteolytic
      activity was significantly inhibited by p-chloromercuribenzoic acid or E-64 but
      not by EDTA or phenylmethylsulfonyl fluoride. Proteolytic activity was enhanced
      threefold in the presence of 8 mM cysteine. These experimental results indicated
      that the enzyme was a thermostable thiol protease.

PMID- 7811093
TI  - Dechlorination of trichlorofluoromethane (CFC-11) by sulfate-reducing bacteria
      from an aquifer contaminated with halogenated aliphatic compounds.
AB  - Groundwater samples were obtained from a deep aquifer contaminated with
      halogenated aliphatic compounds. One-milliliter samples contained 9.2 x 10(5)
      total bacteria (by acridine orange microscopic counts) and 2.5 x 10(3) sulfate
      reducing bacteria (by most probable number analysis). Samples were incubated
      anaerobically in a basal salts medium with acetate as the electron donor and
      nitrate and sulfate as the electron acceptors. Residual levels of
      trichlorofluoromethane (CFC-11) in samples were biotically degraded, while
      trichloroethylene was not. When successively higher levels of CFC-11 were added,
      increasingly rapid degradation rates were observed. Concomitant with CFC-11
      degradation was the near stoichiometric production of fluorodichloromethane (HCFC
      21); the production of HCFC-21 was verified by mass spectrometry. CFC-11
      degradation was dependent on the presence of acetate (or butyrate) and sulfate
      but was independent of nitrate. Other carbon sources such as lactate and
      isopropanol did not support the degradation. The addition of 1 mM sodium sulfide
      completely inhibited CFC-11 degradation; however, degradation occurred in the
      presence of 2 mM 2-bromoethanesulfonic acid. These results indicate that the
      anaerobic dechlorination of CFC-11 is carried out by sulfate-reducing bacteria
      and not by denitrifying or methanogenic bacteria.

PMID- 7811094
TI  - Pseudomonas sp. strain HBP1 Prp degrades 2-isopropylphenol (ortho-cumenol) via
      meta cleavage.
AB  - Pseudomonas sp. strain HBP1 Prp grew on 2-isopropylphenol as the sole carbon and
      energy source with a maximal specific growth rate of 0.14 h-1 and transient
      accumulation of isobutyric acid. Oxygen uptake experiments with resting cells and
      enzyme assays with crude-cell extracts showed that 2-isopropylphenol was
      catabolized via a broad-spectrum meta cleavage pathway. These findings were
      confirmed by experiments with partially purified enzymes. Identification of 3
      isopropylcatechol and 2-hydroxy-6-oxo-7-methylocta-2,4-dienoic acid as the
      products of the initial monooxygenase reaction and the subsequent extradiol ring
      cleavage dioxygenase reaction, respectively, was based on gas chromatography-mass
      spectrometry analysis of the corresponding trimethylsilyl derivatives. The meta
      cleavage product hydrolase hydrolyzed 2-hydroxy-6-oxo-7-methylocta-2,4-dienoic
      acid (meta cleavage product of 2-isopropylphenol) to isobutyric acid and 2
      hydroxypent-2,4-dienoic acid.

PMID- 7811095
TI  - Molecular analysis of mercury-resistant Bacillus isolates from sediment of
      Minamata Bay, Japan.
AB  - Bacillus isolates from Minamata Bay sediment were selected for the ability to
      volatilize mercury from a range of organomercurials (including methylmercury).
      Chromosomal DNA from 74 of 78 such strains hybridized with the mer mercury
      resistance operon DNA from marine Bacillus sp. strain RC607 (Y. Wang, M. Moore,
      H. S. Levinson, S. Silver, C. Walsh, and I. Mahler, J. Bacteriol. 171:83-92,
      1989). The most frequent classes with regard to restriction nuclease site maps of
      the mer operon for the new isolates were identical to or closely related to the
      mer determinant of strain RC607. PCR amplification analysis with primers designed
      from the strain RC607 mer operon gave products of precisely the predicted size
      with the 74 Minamata Bay isolates.

PMID- 7811096
TI  - Incidence of Listeria spp. and Listeria monocytogenes in a poultry processing
      environment and in poultry products and their rapid confirmation by multiplex
      PCR.
AB  - The incidence of Listeria spp. and Listeria monocytogenes in a poultry processing
      plant and in raw and cooked poultry products was determined over a 6-month
      period. Within the raw and cooked poultry processing environments, 46% (36 of 79)
      and 29% (51 of 173) of the samples contained Listeria spp. while 26% (21 of 79)
      and 15% (27 of 173) contained L. monocytogenes, respectively. Various sites
      within the processing environment were found to be consistently positive for L.
      monocytogenes throughout the entire sampling period. Of the raw and cooked
      products tested, 91% (53 of 58) and 8% (8 of 96) were found to contain Listeria
      spp. while 59% (34 of 58) and 0% (0 of 96) contained L. monocytogenes,
      respectively. Although L. monocytogenes was not detected in the cooked products
      examined, the presence of other Listeria spp. highlights the potential which
      exists for postprocessing contamination. Multiplex PCR proved to be a convenient
      and time-saving technique for rapid confirmation of Listeria spp. and L.
      monocytogenes in a single reaction.

PMID- 7811097
TI  - Isolation of three hexahydro-1,3,5-trinitro-1,3,5-triazine-degrading species of
      the family Enterobacteriaceae from nitramine explosive-contaminated soil.
AB  - Three species of the family Enterobacteriaceae that biochemically reduced
      hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and octahydro-1,3,5,7-tetranitro
      1,3,5,7-tetrazocine (HMX) were isolated from nitramine explosive-contaminated
      soil. Two isolates, identified as Morganella morganii and Providencia rettgeri,
      completely transformed both RDX and the nitroso-RDX reduction intermediates. The
      third isolate, identified as Citrobacter freundii, partially transformed RDX and
      generated high concentrations of nitroso-RDX intermediates. All three isolates
      produced 14CO2 from labeled RDX under O2-depleted culture conditions. While all
      three isolates transformed HMX, only M. morganii transformed HMX in the presence
      of RDX.

PMID- 7811098
TI  - Immunological detection of Salmonella paratyphi A in raw prawns.
AB  - A slot blot enzyme-linked immunosorbent assay, using monoclonal antibodies
      specific only for Salmonella paratyphi A, to detect S. paratyphi A contamination
      in raw prawns has been established. When artificially contaminated prawn samples
      were tested. S. paratyphi A contamination could be identified correctly within 20
      h. No false positives from samples artificially contaminated by other
      microorganisms were obtained. The sensitivity was such that as few as 1 S.
      paratyphi A organism per g of raw prawn could be detected. Therefore, the assay
      constituted a promising test for the rapid and specific detection of S. paratyphi
      A in prawns.

PMID- 7811099
TI  - Identification and analysis of the antigens detected by two commercial Bacillus
      cereus diarrheal enterotoxin immunoassay kits.
AB  - The usefulness of two commercial immunoassays for the detection of diarrheal
      enterotoxin of Bacillus cereus is unclear because the identity of the
      enterotoxin(s) has not been proven and the kits detect different proteins. We
      found that the Bacillus cereus Enterotoxin-Reversed Passive Latex Agglutination
      kit (Oxoid) detects the L2 component from hemolysin BL, and the Bacillus
      Diarrhoeal Enterotoxin Visual Immunoassay (Tecra) detects two apparently nontoxic
      proteins.

PMID- 7811100
TI  - Demethylation of dimethylsulfoniopropionate to 3-mercaptopropionate by an aerobic
      marine bacterium.
AB  - A bacterium, strain BIS-6, that grew aerobically on dimethylsulfoniopropionate
      (DMSP) was isolated from an intertidal mud sample. Strain BIS-6 quantitatively
      demethylated DMSP and 3-methiolpropionate to 3-mercaptopropionate. Strain BIS-6
      was a versatile methylotroph growing on the osmolytes DMSP and glycine betaine
      and their methylated degradation products (dimethyl glycine, sarcosine,
      methylamines, and dimethyl sulfide.

PMID- 7811102
TI  - Cloning of organic solvent tolerance gene ostA that determines n-hexane tolerance
      level in Escherichia coli.
AB  - A variety of genes are involved in determining the level of organic solvent
      tolerance of Escherichia coli K-12. Gene ostA is one of the genes contributing to
      the level of organic solvent tolerance. This gene was cloned from an n-hexane
      tolerant strain of E. coli, JA300. A JA300-based n-hexane-sensitive strain,
      OST4251, was converted to the n-hexane-tolerant phenotype by transformation with
      DNA containing the ostA gene derived from JA300. Thus, the cloned ostA gene
      complemented the n-hexane-sensitive phenotype of OST4251.

PMID- 7811101
TI  - Purification and some properties of a xylanase from Aspergillus sydowii MG49.
AB  - Aspergillus sydowii MG49 produces a 30-kDa exosplitting xylobiohydrolase during
      growth on xylan. A specific chemical modification and substrate protection
      analysis of purified xylanase provided evidence that tryptophan and carboxy and
      amino groups are present at the catalytic site of this enzyme. Thermal
      inactivation of the xylanase occurs because of irreversible polymolecular
      aggregation, which is slower in the presence of glycerol.

PMID- 7811103
TI  - Trichloroethylene removal and oxidation toxicity mediated by toluene dioxygenase
      of Pseudomonas putida.
AB  - Whole cells of Pseudomonas putida containing toluene dioxygenase were able to
      remove all detectable trichloroethylene (TCE) from assay mixtures. The capacity
      of cells to remove TCE was 77 microM/mg of protein with an initial rate of
      removal of 5.2 nmol/min/ng of protein. TCE oxidation resulted in a decrease in
      the growth rate of cultures and caused rapid cell death. Addition of
      dithiothreitol to assay mixtures increased the TCE removal capacity of cells by
      up to 67% but did not prevent TCE-mediated cell death. TCE induced toluene
      degradation by whole cells to a rate approximately 40% of that induced by toluene
      itself.

PMID- 7811104
TI  - Use of fluorescein-di-beta-D-galactopyranoside (FDG) and C12-FDG as substrates
      for beta-galactosidase detection by flow cytometry in animal, bacterial, and
      yeast cells.
AB  - Fluorescein-di-beta-D-galactopyranoside (FDG) was found to be a useful substrate
      for beta-galactosidase detection by flow cytometry in gram-negative bacteria,
      since it entered viable cells and gave a fluorescence emission proportional to
      the enzymatic activity. C12-FDG, a more lipophilic derivative, gave a very poor
      signal because of the lack of penetration. On the contrary, C12-FDG was more
      sensitive than FDG for beta-galactosidase activity determinations in animal
      cells. In contrast to previous reports, C12-FDG did not enter viable yeast cells,
      so that the use of the substrate required cell permeabilization. Without this
      treatment, C12-FDG penetrates only nonviable yeast cells that may occur in
      populations expressing beta-galactosidase.

PMID- 7811105
TI  - Cloning, sequencing, and regulation of a xylanase gene from the fungus
      Aureobasidium pullulans Y-2311-1.

PMID- 7811106
TI  - Mercury accumulation in largemouth bass (Micropterus salmoides) in a Florida
      lake.
AB  - Rates of mercury accumulation were examined in male and female largemouth bass
      (Micropterus salmoides) from Lake Tohopekaliga, Florida, to establish methods for
      fish consumption advisories for the protection of human health. In addition,
      concentrations were determined in five lower trophic level fish species. Total
      mercury concentrations in adult largemouth bass muscle tissue ranged from 0.16 to
      1.10 micrograms/g (fresh weight) and increased as fish increased in size and age.
      Whole-body mercury concentrations of 1990 year-class largemouth bass increased
      from 0.05 microgram/g at 20 mm and to 0.32 microgram/g at 320 mm (age 2).
      Significant differences were found in the rates of accumulation between sexes for
      length and weight, but not for age. Therefore, standardized mercury
      concentrations were determined using bass age to make comparisons among sampling
      dates. Although there were significant differences in adjusted mean mercury
      concentrations among two sampling dates, mercury content of standard-age bass
      remained relatively constant over time. Largemouth bass exceed the Florida Health
      Advisory level for limited consumption of fish (0.50 microgram Hg/g) based on a
      mean concentration of 0.59 microgram/g for 64 bass. Advisories based on fish
      morphological characteristics (i.e., length, weight) or age are not possible for
      Lake Tohopekaliga due to differences in mercury accumulation in male and female
      bass. Lower trophic level species of sport fish did not exceed the limited
      consumption level.

PMID- 7811107
TI  - Heavy metals in the hair of opossum from Palo Verde, Costa Rica.
AB  - Levels of lead, cadmium, mercury, chromium, and manganese were measured in the
      hair of opossum (Didelphis virginiana) from Palo Verde, Guanacaste, Costa Rica.
      This area has some agriculture, but is slated for extensive water development
      that will increase ecosystem exposure to a variety of agricultural chemicals.
      Metal levels were generally not intercorrelated except for chromium and lead,
      chromium and cadmium, and cadmium and lead. There were significant gender
      differences only for lead and chromium, with the significantly smaller females
      having higher levels. It is suggested that hair from mammals, particularly
      abundant ominivores may be useful, bioindicators of environmental quality over a
      long time period.

PMID- 7811108
TI  - Bioaccumulation of aromatic hydrocarbons from sediments: a dose-response study
      with flounder (Pseudopleuronectes americanus).
AB  - Pseudopleuronectes americanus were chronically exposed to Hibernia crude oil in
      sediments, for 4 months. Oil was added to sediments at five concentrations
      between 0.09 and 4.5 mg/g (dry weight) and was 0.10-0.90 mg/g, at the termination
      of the exposure. Bioaccumulation measured in terms of fluorescence or in terms of
      the concentration of specific aromatic targets, increased with dosage.
      Accumulation of hydrocarbons was observed in muscle tissue (0.22 microgram/g, dry
      weight), when concentration of the sum of 27 polycyclic aromatic compounds (PAC)
      in sediments was of 0.65 microgram/g (E-50), at the end of the 4-month period. Of
      the 27 parental and alkylated polycyclic aromatic compounds analyzed, alkylated
      naphthalenes predominated in muscle (90-100%) and in sediments (30-60%).
      Bioaccumulation factors were derived for 13 compounds detected in muscle, at the
      three higher exposures. Liver concentrations (fluorescence) were higher than in
      muscle, but did not display a noticeable dose-response. Several alkylbenzenes, a
      C-2 biphenyl and C-4 acenaphthene were also detected in muscle extracts. The
      development of dose-response relationships for polycyclic aromatic hydrocarbons
      (PAH) present in sediment, in relation to bioaccumulation in flatfish, is of
      major interest for evaluating the environmental effects of oil contamination.

PMID- 7811109
TI  - Accumulation and persistence of individual polychlorinated biphenyl congeners in
      liver, blood, and adipose tissue of rats following dietary exposure to Aroclor
      1254.
AB  - Female F344/NCr rats were exposed continuously to Aroclor 1254 (1, 3.3, 10, 33,
      or 100 ppm in the diet) for 7, 28, or 84 days in order to assess the accumulation
      of polychlorinated biphenyls (PCBs) in liver, blood, and adipose tissue. The
      persistence of the individual PCB congeners which are detected in liver was
      examined in the three tissues of additional groups of rats exposed for 7 days
      followed by 21 days on control diet, or for 28 days followed by 56 days on
      control diet. Limited accumulation of PCB congeners with low chlorine
      substitution (tri- and tetrachlorobiphenyls) in the liver and blood, and
      preferential retention of highly substituted PCB congeners (penta- and
      hexachlorobiphenyls) were observed in rats continuously exposed to Aroclor. In
      these rats, time- and dose-dependent increases in the relative levels of two
      congeners which cause profound phenobarbital-type induction [2,2',3,4,4',5'
      hexachlorobiphenyl (BZ# 138) and 2,2',4,4',5,5'-hexachlorobiphenyl (BZ# 153)]
      were detected in the liver and adipose tissue. Rats receiving control diet
      following Aroclor treatment displayed a time- and dose-dependent decrease in the
      relative levels in blood, adipose and hepatic tissue of 2,3,3',4,4'
      pentachlorobiphenyl (BZ# 105) and 2,3',4,4',5-pentachlorobiphenyl (BZ# 118), two
      of the major congeners showing both TCDD- and phenobarbital-type induction. These
      rats also displayed increases in the relative adipose levels of another
      relatively potent mixed-type inducer, 2,3,3',4,4',5-hexachlorobiphenyl (BZ# 156),
      and increases in adipose and hepatic levels of the pure phenobarbital-type
      inducer, 2,2',4,4',5-pentachlorobiphenyl (BZ# 99).

PMID- 7811110
TI  - Characteristics of a white-footed mouse (Peromyscus leucopus) population
      inhabiting a polychlorinated biphenyls contaminated site.
AB  - Demographic characteristics of a white-footed mouse (Peromyscus leucopus)
      population inhabiting a woodland containing a low level of PCBs contamination
      were compared to an uncontaminated reference site. Although population density
      was higher on the PCBs-contaminated grid, the population exhibited greater
      temporal variability among years and had a higher number of transient animals.
      These population trends are consistent with those observed in structurally
      suboptimal habitats, indicating that the PCBs-contaminated grid is functioning as
      a suboptimal habitat. However, the data are not compelling enough to firmly
      conclude that the differences are due to contamination rather than to undetected
      environmental variation between sites. If demographic differences due to
      contamination are slight, they will be difficult to detect against a background
      of demographic variation resulting from subtle environmental differences. We
      conclude that animals at this site experienced a level of contamination that was
      below threshold for unequivocal detection of demographic effects.

PMID- 7811111
TI  - Reproductive transfer and variation of body load of organochlorine pollutants
      with age in fin whales (Balaenoptera physalus).
AB  - The body load of tDDT (p,p'DDT + o,p'DDT + p,p'DDE + p,p'TDE) and polychlorinated
      biphenyls (sum of congeners) was estimated for 169 fin whales to study age and
      sex-related variation and to calculate the quantity of these compounds
      transferred to offspring through reproduction. Blubber was the body compartment
      containing the greatest quantities of organochlorines, but its relative
      contribution to total load was lower than in other cetaceans because in fin
      whales muscle and bone are also significant lipid reserve sites. In male fin
      whales, organochlorine body loads increased with age but tended to reach a
      plateau in fully grown individuals. In adult females, loads decreased with age
      because of transfer to offspring cancelling the rise in loads associated with
      body growth; as a consequence, the amount of organochlorines transferred during a
      reproductive cycle also declined with age. This transfer is lower than that found
      for other cetaceans because fin whales have a shorter lactation period. According
      to the calculations, the first offspring of a female fin whale receives about 1 g
      of PCB and about 1.5 g of tDDT. These amounts will progressively decrease in
      subsequent reproductive cycles to reach a minimum of 0.2 g PCB and 0.3 g tDDT in
      an old female. Therefore, the first calf delivered is the one most likely to be
      affected by pollutants.

PMID- 7811112
TI  - [Varioliform gastritis or lymphocytic gastritis? Anatomoclinical study. Apropos
      of 14 cases].
AB  - The authors report 14 cases of lymphocytic gastritis, 13 of which correspond to
      an endoscopic appearance of varioliform gastritis. Epigastric pain was present in
      91.6% of cases. Varioliform pattern corresponded to an antral site in 69.2% of
      cases and to the body in 30.8% of cases. Lymphocytic gastritis was diagnosed in 7
      cases (46%), 6 of which corresponded to a varioliform gastritis. An associated
      duodenal ulcer was noted in 28.5% of our cases of lymphocytic gastritis.

PMID- 7811113
TI  - [Multifocal germ cell tumors].
AB  - A 16-year old male presented with a mediastinal germ cell tumor (seminoma)
      treated by combined surgery, radiotherapy and chemotherapy. Nine years later, he
      presented with an intracerebral germ cell tumor affecting both the suprasellar
      ventricles and the pineal area. After partial removal of the intraventricular
      tumor, the patient received radiotherapy and chemotherapy. No metastases could be
      found. He died 8 months later, probably from secondary cardiovascular
      disturbances. This case seems to be the first one to illustrate the possibility
      of multifocal extragonadal seminoma.

PMID- 7811114
TI  - [Encapsulated papillary carcinoma of the thyroid gland. Particular histological
      aspect of a case with review of the literature].
AB  - The authors report a case of encapsulated papillary neoplasm in the right lobe of
      the thyroid of a 36-year-old woman. This neoplasm was a papillary encapsulated
      carcinoma with variable histologic patterns not properly described in the
      literature. In the light of a review of the literature, the authors stress the
      macroscopic and histologic aspects of this tumor and they discuss the prognosis
      and therapeutic tools used to cure this neoplasm.

PMID- 7811115
TI  - [Melanosis of the prostate. A new case and review of the literature].
AB  - Melanin may be found within fibromuscular prostatic stroma and/or in prostatic
      epithelium. An example of prostatic melanosis, with histochemical and
      immunohistochemical studies is reported. The pathologic description and the
      histogenesis of this rare entity are discussed.

PMID- 7811116
TI  - [Brain metastasis of a cutaneous neuroendocrine carcinoma. Apropos of a case].
AB  - The authors report the case of a 69-year-old woman with a brain metastasis from a
      cutaneous neuroendocrine carcinoma. The initial lesion was situated on the leg.
      No other secondary lesion was found. The cutaneous neuroendocrine carcinoma was
      initially considered to be a locally malignant tumor. In fact, it is frequently
      complicated by metastases. However, brain secondaries remain rare.

PMID- 7811117
TI  - [Prion diseases in men].
AB  - Since the outbreak of "mad cow disease" and, more recently, the occurrence of
      cases of iatrogenic Creutzfeldt-Jakob disease in children who received pituitary
      extracts, there has been increasing public awareness and concern regarding the
      spongiform encephalopathies. These disorders appear to be caused by an
      extraordinary agent, unlike any previously described, called a "prion". All are
      progressive dementing diseases which are not associated with any specific immune
      or inflammatory response. At present there is no effective treatment.

PMID- 7811118
TI  - [Multiple endocrine neoplasia type I. Review and presentation of the study group
      of multiple endocrine neoplasia type I (GENEM I)].
AB  - Multiple endocrine neoplasia type I, also known as Wermer's syndrome, is
      characterized by the presence of functioning or nonfunctioning tumors or
      hyperplasia of the parathyroid glands, pancreatic islet cells and pituitary
      gland. MEN I syndrome may be either familial or sporadic. MEN I locus has
      recently been mapped to chromosome 11, and further characterization of the
      abnormal gene appears imminent. The GENEM I, a multidisciplinary study group is
      in the process of formation. Pathologists have to specify the morphological
      criteria of hyperplasia vs tumor. Further characterization of the gene and its
      product requires the application of molecular biology methods to the pathologic
      tissues of these patients.

PMID- 7811119
TI  - [Non-seminomatous germ cell tumors of the testis. Role of the pathologist in the
      assessment of prognostic factors based on the specimen of orchiectomy. Proposal
      of an anatomopathological examination report defined by the Study Group of the
      Committee of Cancerology of the French Association of Urology].
AB  - Non-seminomatous germ cell tumors of the testis. Role of the pathologist in the
      definition of the prognostic factors based on examination of the orchidectomy
      specimen. Proposal of a pathological examination report form defined by the study
      Group of the Oncology Committee of the French Urological Association.

PMID- 7811120
TI  - [Congenital cystic adenomatoid malformation of the lung. Apropos of 7 cases].
AB  - Seven new cases of congenital cystic adenomatoid malformation of the lung have
      been observed in our institution during the past twelve years. The diagnosis was
      made in five cases on stillborn fetuses between 16 to 23 weeks of gestation and
      in two cases in a three-day-old infant and in a two-month-old baby. Adopting the
      histological classification proposed by Stocker, the seven cases observed were
      type II. A review of the literature on this malformation reveals the most
      important characteristics of this entity (clinical aspects, macroscopic and
      microscopic features, associated malformations) and provides certain elements of
      the pathogenesis which remains unclear. Finally, only histological examination
      can confirm the diagnosis of this malformation.

PMID- 7811121
TI  - [Periosteal osteosarcoma of the jaw. Apropos of 2 cases].
AB  - The authors report two cases of periosteal osteosarcoma of the jaws, a tumour
      which is one of the two variants of juxtacortical osteosarcoma. Periosteal
      osteosarcoma involving the jaw bones is extremely rare. Because of its
      chondroblastic differentiation, sometimes predominant, this tumour may pose some
      problems of differential diagnosis with chondrosarcoma or pleomorphic adenoma:
      immunochemistry may be necessary. This localization does not change the clinical,
      radiologic, histologic and prognostic features of periosteal osteosarcoma.

PMID- 7811123
TI  - Management of cardiac arrhythmias with radiofrequency catheter ablation.
AB  - Radiofrequency energy has emerged as the current energy source of first choice
      for ablation procedures. We review the development of radiofrequency energy for
      ablation procedures and its advantages and disadvantages. We also review how
      radiofrequency energy can be applied to treat various arrhythmias. We also
      discuss some of the insights that catheter ablation has in turn provided in our
      understanding of arrhythmias.

PMID- 7811122
TI  - Managed care and managed death.

PMID- 7811124
TI  - Antithrombotic therapy. An abbreviated reference for clinicians.
AB  - Antithrombotic therapy is a mainstay in the treatment of patients with
      thromboembolic diseases of the arterial and venous circulatory systems. Continued
      work and investigation has provided much-needed information directly applicable
      to meeting high standards of patient care. The American College of Chest
      Physicians Consensus Conference on Antithrombotic Therapy has been instrumental
      in developing guidelines. This article is a synopsis of the proposed guidelines,
      including recent updates and information that will likely influence future
      recommendations.

PMID- 7811125
TI  - Ambulatory electrocardiography. A cost per management decision analysis.
AB  - BACKGROUND: This study evaluated the current clinical use and costs of ambulatory
      electrocardiographic (AECG) monitoring for arrhythmia detection based on a cost
      per management decision analysis. METHODS: Consecutive inpatient and outpatient
      24-hour AECGs (n = 650) performed during the calendar year 1991 were
      retrospectively reviewed for clinical indication, arrhythmia detection, diary
      information, and whether a management decision that might alter patient outcome
      was derived from the data. The cost per management decision (based on a
      representative reimbursement of $550 per AECG) and the cost index (CI) (all tests
      divided by useful tests) were calculated. RESULTS: Although arrhythmias were
      identified in 91% of the patients, management decisions were indicated in only
      18% (cost per decision, $2974; CI = 5.4). Management decisions were most often
      derived from the data in patients being evaluated for arrhythmia therapy (37 of
      37 patients; cost per decision, $550; CI = 1). Symptoms and arrhythmias were
      correlated in only 11 patients (2%). More often typical clinical symptoms were
      present (26 patients) in the absence of an arrhythmia. Of 101 AECGs following a
      cerebrovascular event, four had unsuspected atrial fibrillation (cost per
      decision, $13,888; CI = 25.0). Dizziness or lightheadedness associated with other
      cardiac symptoms was more likely to lead to a management decision than the same
      symptoms in isolation (29% vs 7%; P < .05). No patient had central nervous system
      symptoms correlated with an arrhythmia during the recording period or unsuspected
      ventricular tachycardia. CONCLUSION: Ambulatory electrocardiography has a highly
      variable and indication-dependent effectiveness and cost. The results suggest a
      strategy for improving the use of AECG based on knowing what testing indications
      are more likely to lead to useful clinical information.

PMID- 7811126
TI  - Living wills and resuscitation preferences in an elderly population.
AB  - BACKGROUND: Living wills are considered clear and convincing evidence of a
      person's preferences for end-of-life treatment. Unfortunately, living wills often
      use vague language that forces physicians and others to infer specific treatment
      choices, like the choice to forgo cardiopulmonary resuscitation (CPR). To test
      the validity of such inferences we examined the relationship between living will
      completion and CPR preference. We also examined whether CPR choices were fixed or
      could be influenced by detailed information on CPR. METHODS: We interviewed 102
      retired elderly persons, many of whom had living wills. We obtained CPR
      preferences in five hypothetical scenarios before and after providing CPR
      information. We then analyzed differences in desire for CPR between the group of
      subjects with living wills and the group without. RESULTS: In each scenario there
      were subjects in both groups who desired CPR. The group with living wills desired
      less CPR in scenarios involving functional impairment and cognitive impairment,
      but not in scenarios involving current health, severe illness, and terminal
      illness. After receiving CPR information, both groups changed their preferences
      such that intergroup differences were no longer seen. CONCLUSIONS: Preferences
      for CPR among subjects with living wills are not homogeneous, but distributed
      across the clinical scenarios. Therefore, one cannot infer CPR preference from
      the mere presence of a living will. Cardiopulmonary resuscitation information can
      influence preferences even among persons with living wills, implying that
      preferences are neither fixed nor always based on adequate information.
      Physicians should view vaguely worded documents as unreliable expressions of
      treatment preference that should not supplant informed discussion.

PMID- 7811127
TI  - The natural history of the pituitary incidentaloma.
AB  - BACKGROUND: The wide availability of computed tomography and magnetic resonance
      imaging has resulted in the discovery of unsuspected endocrinologically silent
      pituitary masses (incidentalomas). Because the natural history of this entity is
      not known, the approach to the pituitary incidentaloma has not been established.
      OBJECTIVE: To determine the natural history of untreated pituitary incidentaloma,
      recognizing that this includes lesions of various causes. METHODS: Thirty-one
      adults with incidentalomas were prospectively followed up conservatively for a
      mean of 6.4 years (range, 3 to 11 years). Clinical and biochemical assessment,
      computed tomography or magnetic resonance imaging of the pituitary, and visual
      field testing by Goldmann perimetry at baseline, 6 months, and yearly thereafter
      were the outcomes assessed. RESULTS: Only patients with pituitary incidentalomas
      greater than 10 mm in greatest diameter developed tumor enlargement or
      complications. Three patients developed asymptomatic tumor enlargement. In four
      patients, masses decreased in size. Only two patients developed complications.
      One required subsequent surgery. The only permanent impairment was
      panhypopituitarism following surgery in this patient. CONCLUSIONS: Patients with
      pituitary incidentalomas of unknown causes usually follow a benign course for at
      least 6 years after discovery. Neurosurgical intervention is not initially
      required in the management of is not initially required in the management of
      pituitary incidentalomas, particularly those less than 10 mm, as long as clinical
      observation can be continued.

PMID- 7811128
TI  - Unrecognized human immunodeficiency virus infection in the elderly.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) infection among the elderly has
      not been appreciated in the United States. This is the result of their exclusion
      from targeted HIV-testing programs and the perception that they were not at
      significant risk. METHODS: To assess the extent of HIV infection among elderly
      patients, we retrieved excess serum samples from patients 60 years or older
      without a history of HIV infection who died during a 1-year period at our
      institution. Serum samples were tested for the presence of HIV antibodies and the
      charts of all those found to be infected with HIV were reviewed. RESULTS:
      Thirteen (5.05%) of 257 serum samples were HIV-antibody positive. Six (6.2%) of
      92 men and seven (8.9%) of 78 women between the ages of 60 and 79 years were
      infected with HIV. In this group there was a trend toward more women having HIV
      infection. The death of none of the 13 patients with HIV infection was
      attributable to HIV infection. CONCLUSIONS: Elderly patients from certain high
      HIV seroprevalence communities may be at significant risk of HIV infection. The
      impact of this unrecognized infection on their health, their clinical outcome,
      and their treatment needs further evaluation. The HIV prevention and education
      programs should include the elderly, and further studies of HIV seroprevalence
      among this population should be supported.

PMID- 7811129
TI  - Association of fasting insulin level with serum lipid and lipoprotein levels in
      children, adolescents, and young adults: the Bogalusa Heart Study.
AB  - OBJECTIVE: To assess whether circulating insulin is a major contributor to
      adverse lipid profiles during the transition from adolescence to young adulthood.
      METHODS: The association between fasting insulin levels and serum lipid and
      lipoprotein levels was examined in a cross-sectional survey of 4136 young
      individuals aged 5 to 30 years from a biracial community. RESULTS: Fasting
      insulin levels were strongly and positively correlated with serum triglyceride
      and very-low-density lipoprotein cholesterol levels and negatively correlated
      with high-density lipoprotein cholesterol levels in all age groups (5 to 11, 12
      to 17, 19 to 24, and 25 to 30 years). An increasing impact of insulin level on
      low-density lipoprotein cholesterol level was observed in young adults aged 25 to
      30 years. In multivariate analysis, fasting insulin level was associated with
      very-low-density lipoprotein cholesterol level for most of the age groups in both
      races independently of age, sex, glucose levels, obesity, cigarette smoking, and
      alcohol intake. The independent relationship to low-density lipoprotein
      cholesterol level persisted in young adults aged 25 to 30 years. The independent
      and negative association with high-density lipoprotein cholesterol level remained
      in whites aged 5 to 24 years and blacks aged 19 to 24 years. When individuals
      were divided into tertiles according to insulin concentration and subscapular
      skinfold thickness, the independent effect of insulin level and obesity on
      lipoprotein fractions was also noted. Furthermore, a stronger association of
      insulin level with lipoprotein fractions was observed in obese than in lean white
      males. CONCLUSIONS: These data indicate that an increasing association of insulin
      levels with adverse lipoprotein levels in young adults, especially obese
      individuals, may have adverse consequence for adult cardiovascular diseases.

PMID- 7811130
TI  - Multimedia computer-assisted instruction in cardiology.
AB  - BACKGROUND: Medical education faces problems caused by increasing restraints on
      resources. A multicenter consortium combined simulation and multimedia computer
      assisted instruction (MCAI) to develop unique interactive teaching programs that
      can address a number of these problems. We describe the consortium, the MCAI
      system, the programs, and a multicenter evaluation of technical and educational
      performance. METHODS: The MCAI system uses computer-controlled access to full
      screen, full-motion, and full-color laser disc video in combination with
      digitized sound, images, and graphics stored on removable media. The Socratic
      teaching method enhances interaction and guides learners through the patient's
      history, cardiovascular physical examination, laboratory evaluation, and therapy.
      Self-instruction and instructor-led modes of function are possible. The first
      five programs, based on simulations of specific cardiology problems, were
      distributed to four medical centers. Questionnaires evaluated technical function
      and medical student opinions, while behaviors and scores were automatically
      tracked and tabulated by program administration software. RESULTS: The MCAI
      system functioned reliably and accurately in all modes and at all sites. The
      programs were highly rated. Student ratings, scores, and behaviors were
      independent of institution and mode of use. CONCLUSION: A multicenter educational
      consortium developed a system to produce unique, sophisticated MCAI programs in
      cardiology. Both system and programs functioned reliably at four institutions and
      were highly rated by fourth-year medical students. With this enthusiastic
      reception, the economies and strengths associated with MCAI make it an attractive
      solution to a number of problem areas, and it will likely play an increasingly
      important role.

PMID- 7811131
TI  - Wegener's granulomatosis masquerading as breast cancer.
AB  - We describe a patient with Wegener's granulomatosis whose disease presented as
      pseudotumor of the orbit and a breast mass. Both findings were misinterpreted and
      errors in diagnosis resulted, despite the availability of rapid and accurate
      diagnostic tests for this disease. We report this case to emphasize the more
      unusual presentations of Wegener's granulomatosis.

PMID- 7811132
TI  - Chinese herbal medicine induced acute renal failure.
AB  - A patient with acute interstitial nephritis secondary to ingestion of a Chinese
      herbal medicine adulterated with mefenamic acid is presented. Following
      hemodialysis and cessation of the medication the patient's renal function
      returned to normal.

PMID- 7811133
TI  - Acromegaly and gastrointestinal cancer.

PMID- 7811134
TI  - Aspirin and the risk of digestive cancers.

PMID- 7811136
TI  - The Stengel rule applied to the artificial refeeding of gastrostomy drainage.

PMID- 7811135
TI  - Advance directives, apples and oranges.

PMID- 7811137
TI  - [Simulated powder tattooing in gunshots through glass plates].
AB  - A case of homicide (two shots through a sheet of glass) is reported with regard
      to "pseudo-powder-tattooing" (irregular stippling of skin due to fragments of
      glass). The findings are compared with real powder-tattooing as seen in cases of
      intermediate-range gunshot wounds.

PMID- 7811138
TI  - [Incidence of scalp involvement by Demodex folliculorum Simon ectoparasites in a
      pathologic-anatomic and forensic medicine autopsy sample].
AB  - 29% of unselected pathological and forensic autopsy cases revealed mites of the
      species Demodex folliculorum longus and brevis in hair follicles and sebaceous
      glands of the scalp. The attack by these parasites was equal in male and female
      subjects and correlated to the number of sebaceous glands but not to the density
      of hair follicles. However there was a tendency to an increased number of
      parasites inhabiting the scalp of people of advanced age, dark hair colour or
      with a bald head. A chronic lymphocytic infiltration of the skin was conspicuous
      in more than 70% of cases with Demodicosis folliculorum.

PMID- 7811139
TI  - [Victims of homicide crimes--social conditions and circumstances of the crime].
AB  - 152 autopsies were performed in cases of homicide at the Institute for Legal
      Medicine of the Hannover Medical School and the documents concerning the social
      situation of the victims, the relationship between offenders and victims and the
      circumstances involved in the crime were analyzed. Among the victims who were
      employed, workers and craftsmen followed by the group working in the service
      industry and trade were most commonly involved. Foreigners were victimized in 8%
      of the cases. In 129 cases (88.4%) there was a single and in 11.6% multiple
      offenders. 78.3% of the victims were murdered by a person they knew. Among
      relatives (38.7%), parents were most frequently implicated (56.5%). Arguments
      were the most common reason followed by quarrels within relationships, robbery
      and sexual offences. In most cases, the location of the crime was the home of the
      victim or of the victim and offender. In 92.8% of the cases, the corpse was found
      at the location of the crime.

PMID- 7811140
TI  - [Unusual suicide by gunshot wound to the head with a signal pistol].
AB  - The professional access to weapons plays a role in the choice of suicide
      instruments. Light and signalling ammunition is used by police forces, in the
      military, in sports, and professional navigation. An unusual suicide of a
      shipowner by means of a signal-pistol is presented. The signal cartridge was shot
      into the head. Penetrating the skull the cartridge entered the brain. The burning
      out of the signal-set--taking about 10 seconds--initiated a flat-burning.--This
      case shows once more the dangerous misuse of light and signal ammunition.

PMID- 7811141
TI  - [At first a clear case: homicide by injury to the neck].
AB  - Reported is of a 33 year old female found dead in the basement of her home,
      manifesting strangulation/throttling marks on the neck. The attack on the throat
      was, however, not cause of death but a CO intoxication. This woman was killed by
      direct inhalation of 99% carbon monoxid administered by her husband (via a mask
      or hose). The carbon monoxid was obtained from a gas cylinder normally used for
      medical purposes.

PMID- 7811142
TI  - [Capacity to act after stab and cutting injury].
AB  - Among 31 cases of death by stab or cut from the years 1989 to 1991 a common
      injury pattern cases was brought out and related to surviving-time and the
      capacity to act. The results revealed a short surviving-time if a great blood
      loss can occur in a short time. There was no correlation between the volume of
      blood loss and the capacity to act or the lungs weight. From these cases, three
      cases are reported. First, a single throatcut with cut of the trachea and a
      surviving-time of 30 minutes. Second, one case of a single heart stab in which
      the victim could run about 100 meters, and third, one case of an isolated cut of
      the A. pericardiaca and an estimated surviving-time of 4-12 hours.

PMID- 7811143
TI  - [Traumatic rupture of the aorta diagnosed by transesophageal echocardiography.
      Apropos of a case and review of the literature].
AB  - The authors report the case of subadventitial rupture of the isthmus of the aorta
      due to trauma, diagnosed by transoesophageal echocardiography. The role of
      transoesophageal echocardiography compared with conventional diagnostic
      techniques is discussed. This method of investigation is a very good diagnostic
      tool in cases of closed trauma of the thorax.

PMID- 7811144
TI  - [Value of magnetic resonance imaging in cardiac sarcoidosis. Apropos of a case].
AB  - The authors report the value of magnetic resonance imaging (MRI) in a case of
      cardiac sarcoidosis presenting with syncopal ventricular tachycardia (VT). The
      images were acquired in a monomorphic multiplane echo spin sequence. A 25
      millisecond interval was chosen for the weighted T1 sequence. A second weighted
      T2 sequence using an interval of 70 milliseconds was then performed. The
      acquisitions were recorded in these planes axial, sagittal and coronal. The
      thickness of the sections was 8 mm. MRI was useful in locating the exact site and
      extent of the lesions; this enabled the operators to perform "guided"
      endomyocardial biopsies. In the weighted T1 sequences, these biopsies showed
      zones of increased intramyocardial signal density, more pronounced on the second
      weighted T2 sequences. Moreover, it was possible to follow up the outcome of
      these lesions with steroid therapy and observe their partial regression. These
      non-specific appearances may be observed in all inflammatory conditions but, in
      the context of systemic sarcoidosis, are very suggestive of cardiac involvement.
      In view of the clinical latency of cardiac sarcoidosis and its poor prognosis,
      the non-invasive character of MRI should make this a routine investigation in all
      patients with systemic sarcoidosis.

PMID- 7811145
TI  - [Flecainide exercise induced left bundle branch with chest pain].
AB  - Ischaemia has been the suggested mechanism of simultaneous left bundle branch
      block and chest pain on effort with normal coronary angiography. This hypothesis
      is very controversial and was not the mechanism in the two new cases of this
      syndrome. The two patients in whom effort pain and left bundle branch block were
      observed had been treated for paroxysmal supraventricular tachycardia with
      flecaine. Withdrawal of the anti-arrhtymic resulted in the disappearance of this
      syndrome. In these cases, the ischaemic mechanism could be excluded without
      ambiguity. The flecaine was the only cause of rate-related LBBB by slowing
      conduction in the left bundle branch with no effects on coronary reserve. It
      would seem that LBBB alone was the cause of chest pain. The absence of coronary
      artery disease was confirmed in the first patient and the diagnosis was highly
      improbable in the second.

PMID- 7811146
TI  - [In vitro evaluation of Dibie-Musset vena caval filter].
AB  - The Dibie-Musset (DM) vena caval filter was evaluated on a hydraulic test bench
      reproducing flow conditions in the inferior vena cava: pressure, flow, viscosity,
      diameter and elasticity of the conduit. The results were compared with those
      obtained with the Greenfield filter (GF). In addition to classical measurements
      (captation and loss of load) we measured the velocity profile with a Doppler
      ultrasonic probe proximal and distal to the filter to study flow conditions
      before and after embolisation of clots. In order to circumvent the difficulties
      encountered with the use of real thrombi, chemical gels with visco-elastic
      properties, evaluated by viscosimetry, similar to those of blood clots, were
      used. Clots 45 mm long and 4 mm diameter were injected in several series of
      measurements. The DM filter was stable and did not migrate. In the horizontal
      position (flexible conduit) the DM filter was significantly more effective than
      the GF for less than 5 clots injected successively. The filtration capacity of
      both filters decreased with the number of clots captured. In the vertical
      position (rigid conduit), when there are less than 5 clots injected the two
      devices were perfectly effective. There was no significant difference between the
      two filters when 10 clots were injected. The loss of load resulting from the
      presence of the filter and clots was greater with the DM filter because of the
      greater captation capacity. However, the velocity profile distal to the filter
      was less disturbed with the DM filter because there was a more uniform
      distribution of the clots captured over the surface of the filter.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7811147
TI  - [Patent foramen ovale: an anatomical study. Apropos of 500 consecutive
      autopsies].
AB  - A patent foramen ovale (PFO) was looked for in 500 consecutive adult autopsy
      studies (265 men, 235 women) in which death was due to acquired cardiovascular
      pathology (mainly coronary artery disease); this condition was demonstrated in 73
      cases (42 men, 31 women); 14.6%. A PFO forms a short inter-atrial communication
      (average length 5 mm) directed anteriorly and slightly superiorly, opening in the
      right atrium anteriorly at the junction of the fosse ovale-limbus and in the left
      atrium under membranous fold concave anteriorly, which represents the anterior
      expansion of the valve of the fosse ovale. The average surface area of the PFO is
      0.5 cm2 (range 0.2 to 1.5 cm2). The underlying cardiac pathologies, age, sex, had
      no relation to the frequency of PFO. Of the different analysable anatomical
      features, weight of the heart, atrial size, tricuspid regurgitation, texture of
      the fosse ovale (thickness over 1mm, or thin, transparent membrane), dimensions
      of the Eustachian valve, had no influence on the frequency of PFO. No thromboses
      were observed incarcerated in, in contact with or adherent to the right atrial
      surface of the PFO. Three of the 73 patients with PFO had, shortly before death,
      experienced an embolic cerebrovascular accident: in all 3 cases there was a
      thrombus in the left heart chambers.

PMID- 7811148
TI  - [Early transesophageal echocardiography after mitral valve replacement.
      Significance of minor abnormal signals].
AB  - The aim of this study was to determine the frequency, significance and prognosis
      of small, abnormal, strand-like echos observed by early transoesophageal
      echocardiography after mitral mechanical valve replacement with hemi-disc
      prostheses. One hundred and twenty nine consecutive patients operated between
      October 1988 and June 1992 underwent transoesophageal echocardiography on average
      15 +/- 7 days after surgery. A second transoesophageal echocardiography was
      performed in 52 patients on average 8 months after the first postoperative
      examination. The frequency of small strand-like echos and of non-obstructive
      thromboses of the valve at the initial transoesophageal examination was 43% and
      8.5% respectively. A multivariate analysis showed that the only independent
      predictive factor for prosthetic valve strands was spontaneous intra-atrial
      contrast (p < 0.01). The presence of strands was significantly related to the
      prevalence of early thrombo-embolic events (confirmed non-obstructive valve
      thrombosis and systemic embolism). Strands were observed in 80% of cases with
      early thromboembolic complications compared with only 38% of cases with no early
      thromboembolic events (p < 0.04). Univariate analysis showed that the
      protamine/heparin ratio at the end of cardiopulmonary bypass and the percentage
      of ineffective postoperative heparinisation were higher in patients with these
      small, abnormal echos (p < 0.05 and p < 0.001, respectively). These appearances
      disappear at long-term transoesophageal echocardiographic control examinations in
      about half the cases. The authors conclude that the majority of these small,
      abnormal echos are thrombotic in nature and are associated with a higher
      thromboembolic risk, justifying effective anticoagulation in the first
      postoperative hours whenever possible, considering the risk of bleeding.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7811149
TI  - [Aortic valve replacement after aortic valvuloplasty for calcified aortic
      stenosis. A propos of 104 patients].
AB  - Between February 1987 and December 1990, 104 patients (48 men, 56 women) with an
      average age of 69 years, underwent aortic valve replacement (AVR) after one or
      several percutaneous aortic valve balloon dilatation. Thirty one patients were in
      Class II and 73 patients in Classes III and IV. Twenty two patients had angina
      (16 Class I-II, 6 Class III-IV) and 12 patients had syncope or near syncope on
      effort. The indications of valvuloplasty were: non-definitive contraindications
      of surgery or a surgical risk which was estimated to be excessive (46 patients),
      a personal choice (41 patients). Five patients underwent preoperative dilatation
      because of the high operative risk; 7 patients refused surgery and 5 patients
      were operated as an emergency (2 mas-sive aortic regurgitations, 1 left
      ventricular perforation, 1 cardiogenic shock, 1 endocarditis with cardiogenic
      shock). The inter-val between dilatation and surgery was on average 472 days. The
      patients were improved over an average period of 261 days. Apart form the
      emergency cases, the patients were operated because of restenosis. Surgery
      consisted of 53 mechanical and 51 bioprosthetic valve replacements. There was an
      associated procedure in 17 cases (17 single bypass grafts, 2 double bypass, 1
      triple bypass graft, 1 left ventricular suture, 1 Bigelow procedure, 2 mitral
      valve replacements, 1 tricuspid annuloplasty, 1 carotid endarteriectomy, 1
      replacement of the ascending aorta, 1 closure of ASD). The operative mortality
      was 7 patients (6.7%). The operative findings were 8 lesions related to
      dilatation, mainly valve tears or disinsertions requiring rapid (6 cases) or
      emergency (2 cases) surgery for massive aortic regurgitation.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7811150
TI  - [Informed consent, what information is left after a therapeutic trial?].
AB  - In order to evaluate the outcome of information given to patients included in a
      therapeutic trial after having signed a consent form, 77 patients (68 men, 9
      women with an average age of 57.9 years) included in the IMPACT study
      (multicenter, randomised, double-blind protocol, the main objective of which was
      to assess the antiarrhythmic effect of oral administration of delayed action
      mexiletine in patients with a recent myocardial infarction), answered a
      questionnaire of 85 items. The quantity and degree of comprehension of the
      recalled information at the end of the trial were appreciated from the replies to
      13 questions based on the definition or understanding of the most important
      details of the consent form and on a comprehension score with a maximum value of
      14 points. The global quantity of information recalled after an interval ranging
      from 5 to 21 months was estimated at 60% of the information provided but the
      recall was not uniform according to the different elements of the consent form:
      the aim of the study, the concept of placebo, the nature of the active treatment,
      the randomisation and possible side effects were only correctly apprehended by 40
      to 50% of patients: the type of patient included, the duration of the trial, the
      content of the gelules, the division between treatment/placebo and the concept of
      double-blind were known to 50 to 75% of participants: the sites of the test
      centres, the possibility of unmasking the "blind" are of withdrawing from the
      trial were correctly understood in 75 to 90% of cases. The global average
      comprehension score was 8.7.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7811151
TI  - [Mid-term results of cardiomyoplasty].
AB  - Cardiomyoplasty (CMP) is a technique of circulatory assistance using a
      pediculated latissimus dorsi muscle wrapped around the heart and electrically
      stimulated during systole. Sixty-four patients, aged 15 to 69 years (average 50.8
      +/- 13 years) with cardiac failure underwent CMP between January 1985 and July
      1993. The causes of cardiac failure were : ischaemic heart disease (39 cases),
      dilated cardiomyopathy (18 cases), cardiomyopathy following valvular heart
      disease (2 cases), cardiac tumours (4 cases) and congenital heart disease (1
      case). Twenty-four patients underwent an associated surgical procedure. Intra and
      postoperative intra-aortic balloon pumping was required in 27 cases. Hospital
      mortality (before latissimus dorsi stimulation) was 20.3% (13/64 cases).
      Evaluation of the survivors 12 months after surgery showed an improvement in
      functional class (1.,5 versus 3.3 before CMP ; p < 0.05), in isotopic ejection
      fraction (27 +/- 3% versus 17 +/- 6%, p < 0.05) and cardiac index (2.87 +/- 0.63
      l/min/m2 versus 2.38 +/- 0.41 l/min/m2, p < 0.05). There was no significant
      change in cardiac filling pressures. The number of hospital admissions for
      congestive cardiac failure in operated patients was 0.4 per patient per year,
      compared with 2.5 per patient per year (p < 0.05) before CMP. The preoperative
      predictive factors for late mortality were: permanent functional Class IV (NYHA),
      severe cardiac dilatation (cardio-thoracic ratio greater than 0.60; left
      ventricular end diastolic dimension > 75 mm), an isotopic left ventricular
      ejection fraction < 15%, severe biventricular cardiac failure and irreversible
      pulmonary hypertension. The actuarial 4 year survival rate was 68.3%.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7811152
TI  - [Value of searching ventricular late potentials in patients recovering from
      ventricular fibrillation].
AB  - The prognostic value of ventricular late potentials (VLP) was studied in 38
      survivors of ventricular fibrillation (VF) resuscitated after cardiac arrest.
      Thirty-seven patients had coronary artery disease, 24 within one month of
      myocardial infarction, and one patient had valvular heart disease. There were 7
      deaths within 2 years, including 5 sudden deaths, the average follow-up in the
      remaining patients being 46 +/- 30 months. Bad prognostic factors included low
      left ventricular ejection fraction, anterior myocardial infarction, VF occurring
      after the first 24 hours of myocardial infarction and the presence of VLP. The 2
      year mortality rate was 35% in patients with VLP compared with only 5% when they
      were absent (p < 0.05). The subgroup with the highest risk of death was that of
      anterior myocardial infarcts with VLP (45% 2 year mortality). The clinical
      circumstances surrounding VF were important; patients with clinical and
      electrical signs of ischaemia at the time of VF tended to have a better prognosis
      than the others, especially in the absence of VLP: in this subgroup of 12
      "ischaemic" VFs without VLP the mortality at 2 years was nil, whereas the other
      26 patients had a 27% death rate (0.05 < p < 0.10). Programmed ventricular
      stimulation was only carried out in 14 cases: it showed that the long-term
      mortality was very high (60%) in patients with VLP and inducible ventricular
      tachycardia (VT). Therefore, the implantation of an automatic defibrillator
      device would seem to be justified in patients resuscitated from VF who have both
      VLP and inducible VT, but of no value in cases of "ischaemic" VF without VLP.

PMID- 7811154
TI  - [Descending thoracic aorta: an excellent inflow source for recurrent
      revascularization of the lower limbs].
AB  - Although severe complications after anatomic reconstruction of the abdominal
      aorta are unusual, when they occur, a different strategy is required to treat the
      patient with success and a distinct operation is generally required for a durable
      favourable long term outcome. Late complications after abdominal aortic grafting
      include prosthetic infection, enteric erosion and graft thrombosis. Treatment by
      resection of the infected graft and extra-anatomic reconstruction with axillary
      femoral or axillary-popliteal bypass leaves the patient with an unreliable
      arterial inflow for his lower extremities; in those patients who survive graft
      removal and extra-anatomic bypass, an alternative source of major arterial inflow
      should at least be discussed to effect a permanent repair. The descending
      thoracic aorta has been described as an ideal inflow source for definitive
      intracavitary conversion of extra-anatomic subcutaneous bypasses and as an
      occasional alternative to avoid a densely scarred abdomen or retroperitoneum. Our
      experience with 8 patients includes 7 in whom the aorta had been overseen below
      the renal arteries in a previous operation [after removal of infected graft (n =
      4) and after repair of aorto-enteric fistula (n = 3)]. Our technique of primary
      extra-anatomic reconstruction consists of a right-sided axillo-femoral (
      popliteal) bypass with femoro-femoral crossing graft. This method avoids
      tunneling an extra-anatomic graft in the left thoraco-abdominal region, thus
      facilitating the definitive repair. Preoperative radiographic evaluation of
      inflow and outflow details is essential in these complex cases.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7811153
TI  - [Continuous monitoring of cardiac output by analysis of the pulse contour].
AB  - One method of continuous cardiac output monitoring by analysis of the radial
      pulse contour (Qcp) relates left ventricular stroke volume and systolic blood
      pressure by calculating the impedence characteristic of the aorta (Zao). It was
      assessed during haemodynamic monitoring by comparing it with the thermodilation
      method in the pulmonary artery (Qtd) in 20 patients with cardiac failure due to
      dilated cardiomyopathy (6 cases) and ischaemic cardiomyopathy (14 cases) treated
      by inotropic agents or vasodilators. Over an average monitoring period of 35
      hours 159 measurements of cardiac output were performed by the two methods. There
      was an excellent correlation between the two methods (r = 0.90; p < 0.001; Qcp =
      0.97 Qtd). The systematic error (bias) between the two methods was about 2.5%.
      The accuracy of Qcp compared with Qtd was 12.5%. During infusion with a
      vasoactive agent (Piroximone), the method based on pulse contour analysis did not
      reflect sudden variations in cardiac output. The systematic error between the two
      methods rose to 19% of the value measured, reflecting the lack of adaptation of
      parameters of correction in this situation and which necessitated recalibration
      of Zao at least once after injection of the drug.

PMID- 7811155
TI  - [Postinfarction hibernating myocardium].
AB  - The detection of hibernating myocardium after infarction is important because it
      justifies the discussion concerning the revascularisation of infarcted zones
      irrigated by occluded or severely stenosed vessels, but with an adequate
      collateral circulation to allow hibernation. The detection of hibernating
      myocardium is particularly important in patients without the classical
      indications for revascularisation, such as residual spontaneous ischaemia or
      ischaemia provoked by exercise or pharmacological stress testing. All techniques
      currently in use tend to overestimate the size of the necrosed, fibrous scar,
      compared with the amount of viable myocardium. Improved regional myocardial
      function after revascularisation is the most convincing proof of hibernating
      myocardium but it can only be obtained retrospectively. The detection of a
      reserve of contractility in the necrosed territory by an inotropic stimulus is
      well adapted to the demonstration of stunned myocardium but this method has not
      been proved in hibernating myocardium. Thallium scintigraphy is certainly useful
      in the prospective diagnosis of hibernating myocardium but the protocol of
      examination should be adapted to this specific problem. There is little available
      data concerning the evaluation of hibernating myocardium by positron emission
      tomography: the technical advantages of this method in assessing myocardial
      viability should enable a more accurate evaluation of post-infarction hibernating
      myocardium. Adequate revascularisation of necrosed territories depends on a
      deeper understanding and more precise prospective assessment of postinfarction
      hibernating myocardium.

PMID- 7811156
TI  - [Von Willebrand factor in coronary disease].
AB  - The value of studying factors of haemostasis and thrombosis in patients with
      coronary artery disease is established. The endothelial lesion and evolution of
      the thrombus play key roles in acute coronary syndromes and coronary angioplasty.
      The von Willebrand factor (VWF) is known for its participation in primary
      haemostasis. Deficits of this factor lead to a haemorrhagic syndrome, von
      Willebrand's disease. This glycoprotein is mainly synthesised by the endothelial
      cells. Its polymeric composition allows identification of two types of
      multimeres. The high molecular weight, active multimeres are liberated from the
      endothelium after stimulation by thrombin. Low molecular weight multimeres are
      less active and are secreted continuously. The VWF promotes platelet adhesion and
      facilitates platelet aggregation. Experimental pig models with VWF deficiency
      show that this factor is essential for the constitution of an occlusive thrombus.
      Several physiopathological mechanisms interact to increase VWF concentrations
      during thrombosis: the endothelial lesion, adrenergic stimulation, acute phase
      reaction. Increased VWF concentrations have been reported in many clinical
      situations. The results are most demonstrative in coronary artery disease. The
      VWF is abnormally high from the time of hospital admission in patients with acute
      myocardial infarction and continues to increase up to the 5th day before falling,
      without returning to normal values, at the 15th day. It is a sensitive though not
      specific late diagnostic marker of myocardial infarction. Increased VWF
      concentrations are not proportional to the severity of coronary atherosclerosis.
      They are, however, related to the infarct size, to the inflammatory reaction and
      to the prothrombotic phase.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7811157
TI  - [Deterged large abscess of the aortic valve ring disclosed after infective
      endocarditis].
AB  - The authors report the case of a very large deterged aortic valve ring abscess
      detected at long-term after infective endocarditis during investigation of
      symptomatic consequent aortic regurgitation. The different imaging methods of
      diagnostic import are reviewed with special emphasis on the role of
      transoesophageal echocardiography during infective endocarditis.

PMID- 7811158
TI  - Functioning and well-being outcomes of patients with depression compared with
      chronic general medical illnesses.
AB  - BACKGROUND: Cross-sectional studies have found that depression is uniquely
      associated with limitations in well-being and functioning that were equal to or
      greater than those of chronic general medical conditions such as diabetes and
      arthritis. However, whether these relative limitations persist over time is not
      known. METHODS: We conducted a 2-year observational study of 1790 adult
      outpatients with depression, diabetes, hypertension, recent myocardial
      infarction, and/or congestive heart failure. Change in functional status and well
      being was compared for depressed patients vs patients with chronic general
      medical illnesses, controlling statistically for medical comorbidity,
      sociodemographics, system, and specialty of care. RESULTS: Over 2 years of follow
      up, limitations in functioning and well-being improved somewhat for depressed
      patients; even so, at the end of 2 years, these limitations were similar to or
      worse than those attributed to chronic medical illnesses. Similar patterns were
      observed for depressed patients in the mental health specialty sector and those
      in the general medical sector, but the patients in the mental health specialty
      sector improved more. More severely depressed patients improved more in
      functioning, but even initially depressed patients without depressive disorder
      had substantial persistent limitations. CONCLUSION: Depressed patients have
      substantial and long-lasting decrements in multiple domains of functioning and
      well-being that equal or exceed those of patients with chronic medical illnesses.

PMID- 7811159
TI  - A positron emission tomographic study of simple phobic symptom provocation.
AB  - BACKGROUND: The goal of this study was to determine the mediating neuroanatomy of
      simple phobic symptoms. METHODS: Positron emission tomography and oxygen 15 were
      used to measure normalized regional cerebral blood flow in seven subjects with
      simple phobia during control and provoked states. Stereotactic transformation and
      statistical parametric mapping techniques were employed to determine the
      locations of significant activation. RESULTS: Statistical parametric maps
      demonstrated significant increases in normalized regional blood flow for the
      symptomatic state compared with the control state in the anterior cingulate
      cortex, the insular cortex, the anterior temporal cortex, the somatosensory
      cortex, the posterior medial orbitofrontal cortex, and the thalamus. CONCLUSIONS:
      The results suggest that anxiety associated with the simple phobic symptomatic
      state is mediated by paralimbic structures. Moreover, activation of somatosensory
      cortex may reflect tactile imagery as one component of the phobic symptomatic
      condition.

PMID- 7811160
TI  - Pharmacotherapy of impaired affect in recovering schizophrenic patients.
AB  - BACKGROUND: Prominent and persistent anxiety, depression, and/or negative
      features characterize a substantial minority of recovered or residually psychotic
      schizophrenic outpatients and contribute to poor outcome. Because extrapyramidal
      side effects of typical neuroleptic medications often resemble such features, we
      first systematically studied the contribution of extrapyramidal side effects to
      these problems and their treatment. For patients who remained distressed,
      controlled trials of supplemental thymoleptics were undertaken. METHODS: In trial
      1, 92 distressed (depressed and/or anxious) patients and 36 patients in a defect
      state (patients with negative symptoms) participated in a double-blind,
      intramuscular challenge that compared centrally acting benztropine mesylate with
      peripherally acting glycopyrrolate. In trial 2, 57 distressed patients and 22
      patients in a defect state were randomly assigned to a double-blind, neuroleptic
      medication dose-reduction group. In trial 3, 57 chronically distressed patients
      who were maintained on a low dose of fluphenazine decanoate were randomly
      assigned to a supplemental desipramine hydrochloride, lithium carbonate, or
      placebo group under double-blind conditions for 12 weeks. RESULTS: For patients
      who were already maintained on antiparkinsonian medication, impaired affect was
      not resolved by additional benztropine. Only distressed patients with a family
      history of severe mental disorder (often affective) showed improvement with
      neuroleptic medication dose reduction. Patients in the defect-state group
      reported less dysphoria on a reduced neuroleptic medication dose, but negative
      symptoms persisted. Desipramine improved diverse aspects of mood and residual
      psychoticism, possibly as a prophylaxis against minor affective exacerbations.
      Depression improved in women only. Lithium positively affected multiple indexes
      of anxiety and anxious depression. CONCLUSION: Most often, persistent affective
      impairments are neither resistant extrapyramidal side effects nor
      characterological traits. Thymoleptics improve the nonphasic, chronic types of
      anxiety and depression in contrast to the acute, episodic forms, for which little
      support can be found in the literature.

PMID- 7811161
TI  - Adoption study demonstrating two genetic pathways to drug abuse.
AB  - BACKGROUND: Studies of adoptees have demonstrated that there are two genetic
      factors leading to alcohol abuse and/or dependence (abuse/dependence). In
      addition, environmental factors found in the adoptive family also predict alcohol
      abuse/dependency independently. One study has found evidence that a similar model
      of two genetic factors and independent adoptive family factors were involved in
      drug abuse. Our study was designed to test the hypothesis that genetic factors
      defined by alcohol abuse/dependency and anti-social personality disorder in
      biologic parents were etiologic in drug abuse/dependency and that psychiatric
      problems in adoptive parents were an additional factor associated with drug
      abuse/dependence. METHODS: A sample of 95 male adoptees, separated at birth from
      their biologic parents, were followed up as adults to determine their psychiatric
      diagnosis and their substance use/abuse in a structured interview administered
      blind to biologic parent diagnoses. A high-risk, case-control design was used
      wherein half of the adoptees came from biologic parents known to be alcohol
      abuser/dependent and/or have antisocial personalities (diagnoses from hospital or
      prison records). These adoptees were matched for age, sex, and adoption agency to
      a control group of adoptees whose biologic parents were not found in the hospital
      and prison record search. Adoptive home environment was assessed by structured
      interviews, including psychiatric assessment of both adoptive parents. RESULTS:
      Data were analyzed by log-linear modeling, which showed evidence of two genetic
      pathways to drug abuse/dependency. One pathway went directly from a biologic
      parent's alcoholism to drug abuse/dependency. The second pathway was more
      circuitous, and started with anti-social personality disorder in the biologic
      parent and proceeded through intervening variables of adoptee aggressivity,
      conduct disorder, antisocial personality disorder, and, eventually, ended in drug
      abuse/dependency. Environmental factors defined by psychiatric conditions in
      adoptive families independently predicted increased antisocial personality
      disorder in the adoptee. Adoptees born of alcohol-abusing mothers showed evidence
      of fetal alcohol syndrome, but controlling for this did not diminish the evidence
      for the direct genetic effect between an alcohol-abusing biologic parent and drug
      abuse/dependency in offspring. CONCLUSIONS: This study confirms the model of two
      independent genetic factors involved in drug abuse/dependence and previous
      findings that disturbed adoptive parents are associated with adoptee drug
      abuse/dependency.

PMID- 7811162
TI  - Efficacy and tolerability of serotonin transport inhibitors in obsessive
      compulsive disorder. A meta-analysis.
AB  - BACKGROUND: Questions have been raised regarding the relative efficacy and
      tolerability of the different serotonin transport inhibitors in the treatment of
      obsessive-compulsive disorder. We compared the results from four large
      multicenter placebo-controlled trials of the serotonin transport inhibitors
      clomipramine hydrochloride (N = 520), fluoxetine hydrochloride (N = 355),
      fluvoxamine maleate (N = 320), and sertraline hydrochloride (N = 325) for the
      treatment of obsessive-compulsive disorder. METHODS: Effect size was calculated
      by subtracting the end-point drug treatment mean change from the end-point
      placebo mean change and dividing by the end-point pooled change standard
      deviation. A test for overall differences between effect sizes was conducted,
      followed by all possible pairwise comparisons. The Yale-Brown Obsessive
      Compulsive Scale was the primary outcome measure for all four studies. RESULTS:
      All four agents were significantly more effective than placebo, with clomipramine
      significantly more effective than the other three treatments, which did not
      differ in effect size. A significantly greater percentage of patients treated
      with clomipramine were rated much or very much improved than were patients
      treated with fluoxetine, fluvoxamine, or sertraline. CONCLUSION: While the
      results of this meta-analysis support the superiority of clomipramine, head-to
      head, double-blind comparisons of these compounds would be the best test of
      comparative efficacy and tolerability.

PMID- 7811163
TI  - Test-retest reliability of the Diagnostic Interview Schedule for Children (DISC
      2.1). Parent, child, and combined algorithms.
AB  - BACKGROUND: Previous research has not compared the psychometric properties of
      diagnostic interviews of community samples and clinically referred subjects
      within a single study. As part of a multisite cooperative agreement study funded
      by the National Institute of Mental Health, 97 families with clinically referred
      children and 278 families identified through community sampling procedures
      participated in a test-retest study of version 2.1 of the Diagnostic Interview
      Schedule for Children (DISC 2.1). METHODS: The DISC was separately administered
      to children and parents, and diagnoses were derived from computer algorithms
      keyed to DSM-III-R criteria. Three sets of diagnoses were obtained, based on
      parent information only (DISC-P), child information only (DISC-C), and
      information from either or both (DISC-PC). RESULTS: Test-retest reliabilities of
      the DISC-PC ranged from moderate to substantial for diagnoses in the clinical
      sample. Test-retest kappa coefficients were higher for the clinical sample than
      for the community sample. The DISC-PC algorithm generally had higher
      reliabilities than the algorithms that relied on single informants. Unreliability
      was primarily due to diagnostic attenuation at time 2. Attenuation was greatest
      among child informants and less severe cases and in the community sample.
      CONCLUSIONS: Test-retest reliability findings were consistent with or superior to
      those reported in previous studies. Results support the usefulness of the DISC in
      further clinical and epidemiologic research; however, closely spaced or repeated
      DISC interviews may result in significant diagnostic attenuation on retest.
      Further studies of the test-retest attenuation phenomena are needed, including
      careful examination of the child, family, and illness characteristics of
      diagnostic stability.

PMID- 7811164
TI  - Treatment of postpartum depression with interpersonal psychotherapy.

PMID- 7811165
TI  - Relationship of panic disorder to posttraumatic stress disorder.

PMID- 7811166
TI  - Physical medicine and rehabilitation across the life span.

PMID- 7811167
TI  - Hyperpyrexia associated with sustained muscle contractions: an alternative
      diagnosis to central fever.
AB  - Muscle activity is the principal source of body heat production, and elevated
      core body temperatures may occur in healthy exercising persons. Hyperpyrexia from
      sustained tonic muscle contractions can also occur in a number of pathological
      conditions. The present case of hyperpyrexia associated with dystonic posturing
      and sustained muscle contraction in a child with encephalopathy illustrates the
      importance of recognizing muscular activity in the generation of fever of unknown
      origin following central nervous system injury. The pathophysiology, clinical
      features, and management of this uncommon cause of fever are discussed.

PMID- 7811168
TI  - Gustatory facial sweating subsequent to upper thoracic sympathectomy.
AB  - Gustatory facial sweating has been described as a consequence of upper thoracic
      sympathectomy. Patients may also develop compensatory hyperhidrosis, sensory
      deficits, nipple hypersensitivity, and Horner's syndrome. In this article, we
      have reviewed three patients with reflex sympathetic dystrophy who developed
      gustatory facial sweating subsequent to endoscopic T2 and T3 ganglionectomy. This
      article also discusses the possible mechanisms of gustatory facial sweating.

PMID- 7811169
TI  - Recovery trends over three years following pediatric traumatic brain injury.
AB  - This cohort study investigated the magnitude of neurobehavioral, academic, and
      "real world" deficits over the course of 3 years in children with mild, moderate,
      and severe traumatic brain injury (TBI), and their individually matched controls.
      This series of analyses addresses the history of recovery, tracing changes in
      performance over time. Data on 72 case-control pairs (mild, n = 40; moderate, n =
      17; severe, n = 15) were available for three testing times: 3 weeks, 1 year, and
      3 years after the resolution of post-traumatic amnesia. The same standardized
      battery of tests was used at all testing times. The dependent variables in these
      analyses included individual test results, a variable summarizing results within
      each of 10 neurobehavioral domains, and an overall score across all domains.
      Three statistics were calculated for each variable: (1) the "grand" mean across
      the three testing times; (2) the slope (expressing the linear trend in
      performance); and (3) the change in slope over time (expressing the change in the
      rate of recovery). Use of the differences between case and control scores
      controlled for premorbid factors, maturation, and test-retest effects. Results
      indicate the chronicity of neurobehavioral deficits across all 3 years for
      moderately and severely injured children. They show a strong improvement rate
      during the first year, but a negligible rate of change during the following 2
      years postinjury in most domains. All three of the time components--grand mean,
      slope, and change in slope--have significant Spearman correlations with severity
      ranging up to rho = -.5. Over time, the recovery rate slows down more for those
      with greater brain injury severity. The greatest slowing of recovery occurs in
      Performance IQ, adaptive problem solving, memory, and motor skills, as well as on
      a summary score of overall performance. Given this "plateauing" of recovery,
      achievement of parity with peers by the moderately and severely injured seems
      unlikely. Mildly injured children, however, exhibit negligible deficits or change
      in performance over time.

PMID- 7811170
TI  - Recovery of walking function in stroke patients: the Copenhagen Stroke Study.
AB  - Time course and degree of the recovery of walking function after stroke and the
      influence of initial lower extremity (LE) paresis were studied prospectively in a
      community-based population of 804 consecutive acute stroke patients. Walking
      function and degree of LE paresis were assessed weekly using the Barthel index
      and the Scandinavian Neurological Stroke scale, respectively. Initially, 51% had
      no walking function, 12% could walk with assistance, and 37% had independent
      walking function. At the end of rehabilitation, 21% had died, 18% had no walking
      function, 11% could walk with assistance, and 50% had independent walking
      function. Recovery of walking function occurs in 95% of the patients within the
      first 11 weeks after stroke. The time and the degree of recovery are related to
      both the degree of initial impairment of walking function and to the severity of
      LE paresis, p < .0001. A valid prognosis of walking function in patients with
      initially no/mild/moderate leg paresis can be made in 3 weeks, and further
      recovery should not be expected after 9 weeks. A valid prognosis of walking
      function in patients with initially severe leg paresis or paralysis can be made
      in 6 weeks, and further improvement of walking function should not be expected
      later than 11 weeks after stroke.

PMID- 7811171
TI  - Characterization of gait parameters in adult-onset myotonic dystrophy: abnormal
      hip motion.
AB  - The gait of five patients with myotonic dystrophy was analyzed using light
      emitting diodes and a force plate. When compared with the gait of control
      subjects, that of myotonics suggested weakness of the tibialis anterior and
      triceps surae muscles. Although the myotonics showed no evidence of lower
      extremity myotonia (delayed muscle relaxation following contraction), or of
      weakness of the hip or knee musculature, all had striking abnormalities in their
      hip motion. In contrast to the smooth and consistent extension of the hip
      throughout stance phase observed during gait in control subjects, the hips of
      myotonics oscillated irregularly as they progressed through stance phase
      extension, with considerable variation between legs and during successive
      strides. Excessive use of hip musculature in an attempt to control the
      oscillatory hip motion may contribute to the chronic fatigue associated with
      myotonic dystrophy.

PMID- 7811172
TI  - Bioenergetic comparison of a new energy-storing foot and SACH foot in traumatic
      below-knee vascular amputations.
AB  - In this study, the metabolic performances of a new energy-storing foot (Proteor)
      and of the solid-ankle cushion heel (SACH) are compared. Twelve patients with
      traumatic below-knee amputations (mean age: 50.0 +/- 19.9 years) and 12 patients
      with vascular below-knee amputations (mean age: 73 +/- 7 years) were studied.
      Oxygen uptake (VO2) was measured in all the subjects on a walkway at a self
      selected velocity; only the subjects with traumatic amputation were tested on a
      level treadmill (progressive speed: 2.4-4 and 6 km/h), and then in two randomized
      trials: incline (+5%) and decline walking treadmill test at 4 km/h. Vascular
      explorations were done in the vascular patients: distal pressure measurements,
      pulse plethysmography, transcutaneous oxygen tension. Free walking was improved
      in subjects with traumatic amputation using the energy-storing foot (+6%), with a
      better bioenergetic efficiency (0.24 +/- 0.4mL/kg.m vs 0.22 +/- 0.04mL/kg.m).
      However, in subjects with vascular amputation, this foot did not produce an
      increased free velocity nor an improved energy cost. During the level treadmill
      test, the traumatic amputee subjects showed a decrease of energy expenditure with
      the new prosthetic foot, more significant at sufficient speed (4 km/h): 17.00 +/-
      3.42 vs 14.67 +/- 2.05 mL/kg/min (p < .05). The same effect is shown during the
      incline (19.31 +/- 2.80 vs 16.79 +/- 2.32 mL/kg/min-p < .02) and decline walking
      tests (14.13 +/- 3.64 vs 11.81 +/- 1.54mL/kg/min-p < .02). There is no
      significant difference in cardiocirculatory effects between the two types of
      prosthetic foot. Despite a lower velocity, the subjects with vascular amputation
      exceed 70% of the maximal heart rate, with the cardiocirculatory factor being the
      main cause of walking restriction. The energy-storing foot should be reserved for
      active and fast walkers, whereas the SACH foot seems more suitable for elderly
      patients with amputation with a slow walk.

PMID- 7811173
TI  - The 29th Walter J. Zeiter Lecture. The Scrooge-Van Winkle time machine: suppose
      we awakened tomorrow and there were no more physiatrists...

PMID- 7811174
TI  - Measurement of the medial longitudinal arch.
AB  - Although clinical evidence suggests a causal relationship between arch structure
      and musculoskeletal injury patterns, biological variations in soft-tissue
      structures effect the accuracy of arch-height measurements. Medial longitudinal
      arch (MLA) structure was assessed clinically and radiographically in 100
      consecutive patients with foot problems. Intraclass correlation coefficients were
      calculated for three radiographic parameters and three anthropometric parameters
      of the MLA. Intrarater and interrater reliability estimates for the radiographic
      measurements were uniformly excellent. Intrarater reliability coefficients were
      higher than interrater coefficients for the three tested anthropometric
      parameters. The strengths of associations between anthropometric and radiographic
      data were assessed with Pearson correlation coefficients. The clinically
      determined ratio of navicular height-to-foot length correlated most closely with
      the radiographic indices of MLA structure.

PMID- 7811175
TI  - Incidence of skin breakdown and higher amputation after transmetatarsal
      amputation: implications for rehabilitation.
AB  - The purpose of this study of patients with transmetatarsal amputation (TMA) is to
      describe multiple patient characteristics, including the incidence of subsequent
      skin breakdown and higher amputation, that may influence rehabilitation treatment
      and outcomes. Data were gathered on all patients having a TMA at this facility
      between April 1989 and September 1993. One hundred twenty TMAs were performed on
      107 patients with a mean age of 62.4 +/- 13.8 years. There were 55 men and 52
      women. Thirteen patients (12%) had a bilateral TMA. Twenty-nine patients (27%)
      developed skin breakdown. Of these, 48% occurred within the first 3 months after
      surgery. Thirty patients (28%) required a higher amputation. Of these, 60%
      occurred in the first month after TMA. In addition, this group of patients had a
      high incidence of diabetes mellitus (77%), hypertension (54%), electrocardiogram
      (EKG) abnormalities (60%), congestive heart failure (22%), and prior ipsilateral
      vascular surgery (51%). These results indicate that patients with TMA often
      present with a complicated medical condition and that they are at high risk of
      skin breakdown or higher amputation, especially in the first 3 months after
      surgery. The investigators conclude that patients with TMA may benefit from a
      rehabilitation program emphasizing protection of the residuum during their return
      to functional activities. Additional research is needed to determine optimal
      acute and long-term rehabilitation of patients with TMA.

PMID- 7811177
TI  - Vibratory stimulation for treatment of anejaculation in quadriplegic men.
AB  - Sexual dysfunction and infertility are common problems following spinal cord
      injury. Most men with complete spinal cord lesions do not ejaculate during
      coitus. Vibratory stimulation applied to the frenulum of the penis in six
      quadriplegic male subjects produced ejaculates for intrauterine inseminations.
      Pregnancies occurred in five of the six partners. Vibratory stimulation is a
      relatively safe and effective means to produce an ejaculation in men with
      quadriplegia.

PMID- 7811176
TI  - Increased muscle strength in paralyzed patients after spinal cord injury: effect
      of beta-2 adrenergic agonist.
AB  - The administration of beta-2 adrenergic agonists in experimental animals result
      in an increased strength of skeletal muscle. In this study, we evaluated whether
      a beta-2 adrenergic agonist, metaproterenol, had an effect on muscle size and
      strength in a group of patients with muscular atrophy following spinal cord
      injury. Ten male subjects were randomly divided into 2 groups and agreed to
      participate in a prospective, double-blind, placebo-controlled, and crossover
      study. Metaproterenol (80 mg/day), or placebo, was administered orally for a
      period of 4 weeks. Muscle strength was measured by a force transducer interfaced
      with a microcomputer. Muscle size was calculated and expressed as a cross
      sectional area of upper arm and forearm using a formula. Metaproterenol induced a
      significant increase of muscle strength in both groups of subjects, compared with
      placebo (p < .001). Similarly, there was an increase in a muscle size in the
      forearm following the administration of metaproterenol. Our data indicate that
      beta-2 adrenergic agonists may improve both muscle strength and size in patients
      with muscular atrophy following spinal cord paralysis.

PMID- 7811178
TI  - Exercise training and severe caloric restriction: effect on lean body mass in the
      obese.
AB  - The purpose of this study was to investigate the effects of exercise intensity on
      the body composition of obese subjects during severe caloric restriction. Forty
      obese subjects (33 women, 7 men; 41 +/- 7.7 years; 106 +/- 26kg; body fat > 25%
      men, > 30% women) on a commercially prepared OPTIFAST 420kcal/day supplemented
      fast were randomized into groups that exercised at target heart rates
      corresponding to 40% and 60% of the heart rate reserve (HRR) at the start of the
      program. Training volume was similar for both groups at approximately 300kcal per
      session three times per week for 12 weeks. Body weight, body fat, and lean weight
      were similar for both exercise intensity groups at week one. Overall, body weight
      decreased by 15.3 +/- 6.7 kg (p < or = .05), and body fat decreased by 14.9 +/-
      5.0 kg (p < or = .05) for the 40 subjects, whereas lean weight remained
      unchanged. No significant differences in body weight, body fat, or lean weight
      were observed between the two groups. The results of the current study indicated
      that while on a supplemented 420-kcal/day fast, exercise at 40% and 60% of the
      HRR affected body composition similarly when total training volume was held
      constant at 900kcal/week. Lean weight remained unchanged and accompanied a 14.9
      +/- 5.0-kg decrease in body fat, which may have resulted when the volume of
      exercise (ie, 900kcals/wk) was factored into the exercise prescriptions. These
      results suggest that exercising at 60% of the HRR offers no advantages for body
      composition changes over those obtained from exercising at 40% of HRR when the
      total volume of exercise training is controlled.

PMID- 7811179
TI  - Sleep apnea in patients with hemispheric stroke.
AB  - Sleep pattern and breathing in humans are altered following cerebrovascular
      accidents involving the brainstem. Sleep apnea is a well-established complication
      of stroke involving the brainstem. On the other hand, the effect of cerebral
      stroke on sleep and breathing has not been well defined. The diffuse cerebral
      symptoms such as cognitive deficits, depression or fatigue, after hemispheric
      stroke mimic those present in patients with sleep apnea. To define the breathing
      pattern in patients with stroke involving cerebral hemispheres without brainstem
      lesion and without the prior history of sleep-disordered breathing, we studied 10
      patients within 1 year of their stroke. The data collected during polysomnography
      from the stroke patients were compared with a group of subjects matched for age,
      body mass index, presence of hypertension, and smoking history without stroke.
      Patients with stroke had an abnormal sleep architecture with significantly lower
      slow wave sleep and rapid eye movement (REM) sleep when compared with controls.
      Sleep was fragmented because of the presence of increased respiratory
      disturbances. Stroke patients had a respiratory disturbance index of 52 +/- 10
      events per hour when compared with 3 +/- 1 in controls (p < .05). Majorities of
      respiratory events were obstructive apneas and were associated with arterial
      oxygen desaturations and arousals. The pathogenic mechanism of sleep-disordered
      breathing in patients with hemispheric stroke seems to be related to the
      physiological effect of sleep on already compromised upper airway muscle control.
      Patients with stroke and diffuse cerebral symptoms should be investigated for the
      possibility of sleep-disordered breathing.

PMID- 7811180
TI  - Test-retest reliability of the sensory organization test in noninstitutionalized
      older adults.
AB  - The purpose of this study was to determine the 1-week test-retest reliability of
      the Sensory Organization Test (SOT), using computer-generated scores and loss of
      balance (LOB) episodes in noninstitutionalized older adults. The SOT was
      administered to each subject on two separate days 1 week apart in an out-patient
      clinic. A volunteer sample of 40 individuals who were at least 65 years of age
      participated in this study. The main outcome measures were computer-generated
      scores for the first trial and the average of the three trials in each of the six
      sensory conditions of the SOT; computer-generated composite score of the six
      conditions; LOB on the first trial and any of three trials in each condition. The
      intraclass correlation coefficients (ICC) for the SOT first trial data ranged
      from .15 in Condition 3 to 0.70 in Condition 5. The ICCs for the SOT average of
      three trials ranged from 0.26 in Condition 3 to 0.68 and 0.64 in Conditions 5 and
      6. Percent agreement was 77% to 100% for LOB on the first trial, as well as LOB
      on any of three trials of Conditions 1 through 6. As the conditions became more
      difficult, an increasing number of subjects experienced LOB. Analysis revealed
      fair to good test-retest reliability for computer-generated scores and good
      reliability for LOB across some conditions of the SOT. A modification to the
      current scoring system is suggested which would improve the reliability of the
      computer-generated scores of the SOT.

PMID- 7811181
TI  - Critical evaluation of clinical research.
AB  - This focused review contains a suggested core of material that will help
      residents or practicing physiatrists critically review research papers published
      in the medical literature. Before accepting the results of a clinical trial,
      physiatrists must critique the experimental methods and study design carefully to
      decide whether to include these new ideas into their clinical practice. Medical
      research relies on statistical methodology, and statistics pervade the medical
      literature. This article begins with an introduction to rudimentary statistics.
      Fortunately, most studies depend on a rather small body of statistical concepts.
      The elements of experimental design--clinical trials, randomization, single
      subject design, meta-analysis, epidemiological studies--are presented in a
      concise review. Finally, the elements of statistics and experimental design are
      integrated into a step-by-step method strategy for reading the medical
      literature.

PMID- 7811182
TI  - Unilateral multilevel cervical radiculopathies as a late effect of poliomyelitis.
      A case report.
AB  - A severe left-sided cervical radiculopathy that developed after a work-related
      injury is reported. Because this involved the upper limb opposite to a long
      standing postpolio sequela, it is suggestive of postpolio syndrome. Work-up
      showed left-sided multilevel acquired foraminal stenosis. These unilateral
      degenerative changes were very likely the result of overuse of the cervical
      apophyseal joints, the consequence of the muscle imbalance created by the
      poliomyelitis. It was successfully treated by appropriate surgical decompression.

PMID- 7811183
TI  - Ipsilateral post-cast hypertrichosis and dyshidrotic dermatitis.
AB  - Post-cast hypertrichosis and dyshidrotic dermatitis are not uncommon separately.
      Yet, the simultaneous occurrence of both conditions in an individual is rare. A
      patient with both localized hypertrichosis and ipsilateral dyshidrotic dermatitis
      following multiple fractures and cast application is reported. The clinical
      presentation, management, spontaneous resolution, and/or response to therapy of
      post-cast hypertrichosis and dyshidrotic dermatitis that occurred concurrently in
      an individual were similar to that described when these conditions occur
      independently. The acquired conditions that may be associated with localized
      hypertrichosis are summarized and the postulated mechanisms of pathogenesis for
      dyshidrotic dermatitis are reviewed. The diagnosis of post-cast hypertrichosis in
      this patient was suspected based upon the distribution and temporal association
      of the hypertrichosis to the location and placement of his cast, and confirmed by
      excluding other causes of acquired localized hypertrichosis. Also, the
      possibility that in this individual either the trauma to his bones, the cast on
      his arm, or both had an etiologic role in promoting the development of
      dyshidrotic dermatitis is suggested.

PMID- 7811184
TI  - Enzyme-cytochemistry of human chorion laeve at term: enzyme localization on the
      chorionic trophoblast.
AB  - Is the chorion laeve merely a remnant of the chorion frondosum in placental
      development? Or is it metabolically active, having something to do with
      maternofetal interactions? In order to answer these questions at least in part,
      we determined the ultracytochemical localizations of some important enzymes such
      as nonspecific phosphatase (alkaline phosphatase), specific phosphatase (Ca(++)
      ATPase and 5'-nucleotidase) and adenylate cyclase in the human chorion laeve at
      term. Strong activities of these enzymes were localized by ultracytochemistry on
      the plasma membrane of the trophoblast in the chorion laeve. These enzyme
      activities were confirmed by a series of cytochemical-control experiments, i.e.,
      substrate-free control, heat-stability control, and inhibition control by
      inhibitors of alkaline phosphatase. These observations indicate that the
      chorionic trophoblast is probably metabolically active and that it might play an
      important role in the physiology of the fetal membrane.

PMID- 7811185
TI  - Clinical usefulness of low-dose oral contraceptives for the treatment of
      adolescent hyperandrogenemia.
AB  - In the early stage of adolescence, irregular menstruation and an anovulation
      often occurs. During this period, some adolescent women suffer from
      hyperandrogenemia, which results in acne, adiposity, and hirsutism. If adequate
      treatment is not given to these hyperandrogenic young women, severe hirsutism and
      polycystic ovary (PCO), which could be a proximate cause of juvenile endometrial
      carcinoma, might occur. Young women with hyperandrogenemia show increased levels
      of luteinizing hormone (LH) levels and free testosterone (T)/total T ratio, and a
      decreased level of steroid hormone binding globulin (SHBG) in serum. Low-dose
      oral contraceptives might reduce the hormone unbalance and hyperandrogenemia
      without leading to negative effects in the ovarian function of adolescent women.

PMID- 7811186
TI  - Neonatal narcotic withdrawal in Hong Kong Chinese.
AB  - A retrospective case controlled study was carried out to study the neonatal
      characteristics, outcome and narcotic withdrawal syndrome in 51 neonates exposed
      to narcotic antenatally. The birth weight, head circumference and body length
      were significantly smaller in the study group while the incidence of prematurity
      (41%) and small-for-gestational age babies was increased (27.5%). Narcotic
      withdrawal occurred in 83% of narcotic exposed neonates. About half of them had
      onset of withdrawal symptoms within the first 24 hours. All of these newborns
      were treated by either phenobarbitone (45%), chlorpromazine (9.5%) or both
      (40.5%). The average duration of treatment was 15.7 days. There was one neonatal
      death due to in utero withdrawal and hypoxia, and another post-neonatal death due
      to sudden infant death. Neonatal jaundice, necrotising enterocolitis, clinical
      sepsis and congenital syphilis were more common in the drug-addicted group.

PMID- 7811187
TI  - Adenosquamous carcinoma arising in a mature cystic teratoma of the ovary: a case
      report and review of the literature.
AB  - A 57-year-old woman with Stage Ia adenosquamous carcinoma arising in a mature
      cystic teratoma was presented. Pathologically, poorly differentiated squamous
      cell carcinoma and mucoepidermoid carcinoma were intermingled in the solitary
      nodule inside of the cyst. She received chemotherapy after operation (total
      abdominal hysterectomy, bilateral salpingo-oophorectomy, and omentectomy). She is
      living without evidence of disease 3 years post-treatment. Adenosquamous
      carcinoma is a rare malignant component in mature cystic teratomas. We reviewed 7
      cases of this cancer arising in mature cystic teratomas, including this case.
      Three cases with Stage Ia were living and well for 9 months to 5 years. Three
      other cases with Stage Ic, II, and IIIc died of their disease at 6, 13 and 2
      postoperative months, respectively. These results might suggest that the
      prognosis of the tumor is worse in advanced stages than that of squamous cell
      carcinoma in mature cystic teratomas.

PMID- 7811188
TI  - A case report on radiotherapy in choriocarcinoma: a life saving procedure.
AB  - Radiation therapy was tried to control hemorrhage from uterine cavity in a case
      of choriocarcinoma in which surgery was not practically possible due to the
      presence of a large nodule extending from suburethral region up to anterior
      fornix involving the entire anterior vaginal wall and patient being in a very
      critical condition. Radiotherapy was found to be successful and life saving.

PMID- 7811189
TI  - Prediction of pregnancy-induced hypertension by isometric exercise.
AB  - The purpose of this study is to evaluate an isometric exercise (Hand-Grip test)
      as a method to predict pregnancy-induced hypertension (PIH). One hundred and
      twenty-five pregnant women were given the Hand-Grip (HG) test before the 15th
      gestational week. The Hand-Grip test was rated positive when the systolic blood
      pressure increased 15 mmHg or more during isometric exercise or decreased 14 mmHg
      or more immediately after isometric exercise. As a result, the Hand-Grip test had
      the highest sensitivity (81.8%) and specificity (68.4%) for predicting PIH,
      compared to other risk factors. The positive predictive value was 20% (second
      highest among risk factors, the actual incidence of hypertension was 8.8%), and
      the negative predictive value was 97.5% (highest). In conclusion, by use of a
      very simple Hand-Grip test early in gestation, we are able to predict PIH with
      the highest sensitivity.

PMID- 7811191
TI  - Spontaneous perforation of pyometra: a case report.
AB  - Spontaneous perforation is a rare complication of pyometra and is usually
      associated with uterine cervical occlusion. We report a very rare case of
      spontaneously perforated pyometra without cervical occlusion. A 56-year-old woman
      with severe abdominal pain was admitted to our hospital. Exploratory laparotomy
      was performed because of suspicion of gastro-intestinal perforation with
      generalized peritonitis. There was no perforation of the stomach, gallbladder, or
      bowels, but examination of the uterus revealed a perforation of the uterine
      fundus. A total abdominal hysterectomy with bilateral salpingo-oophorectomy was
      performed. Pathological investigation of the surgical specimen revealed
      endometritis and myometritis of the uterus; but there was no evidence of
      malignancy, and the cervical canal was patent. Although spontaneously perforated
      pyometra is rare, the condition must be born in mind with regard to elderly women
      with acute abdominal pain.

PMID- 7811190
TI  - Extra gonadal germ cell tumours: report of two cases.
AB  - Extra gonadal germ cell tumours (EGGCT) in women are rare. We report here two
      such patients. The clinical and laboratory features were--young age, 25 and 22
      years, midline location (mediastinum, scalp), elevated tumour marker and normal
      ovaries on CAT scan. The histological subtype was embryonal carcinoma in both
      cases. Complete response (CR) was achieved with cisplatin based chemotherapy
      (CT). Both patients had return of normal ovarian functions and have delivered
      normal babies (1st patient one, 2nd patient 2 babies). Both remain asymptomatic
      and disease-free at 30 + and 55 + months follow-up. We conclude that patients
      with EGGCT after treatment with cisplatin based CT achieve CR with return of
      normal ovarian functions and prolonged survival.

PMID- 7811192
TI  - Trabecular bone in long-term depot-medroxyprogesterone acetate users.
AB  - A cross-sectional study was designed to determine trabecular bone density in 75
      long-term depot-medroxyprogesterone acetate (DMPA) users (> 3 yr) matched with
      non-DMPA users by age, body mass index (18-25), limitation of age (< 45 yr), and
      body weight (< 60 kg). The long-term DMPA cases were divided into 3 groups
      according to duration of injectable contraceptive use. Neither cases nor controls
      had a smoking or chronic alcohol consumption history. Cases and controls were
      matched by age. Trabecular bone of the femoral neck were assessed by X-ray and
      interpreted by a single-blinded radiologist. Trabecular bone patterns were graded
      according to Singh's Index. Blood collection for determination of estradiol,
      prolactin, calcium, phosphorus, and medroxyprogesterone acetate were performed in
      cases and controls. Venous blood was taken at twelfth week of injection of DMPA
      and within 5 days after menstrual bleeding cessation in the controls. Mean
      trabecular bone in the cases was 5.5 +/- 0.6 (range 4-6). It was not
      statistically different from that in the controls (mean 5.5 +/- 0.6, range 2-6).
      No statistically significant difference of serum, calcium, phosphorus, prolactin,
      and estradiol was seen in the cases when compared to controls at mid follicular
      phase of normal menstrual cycle. Serum MPA of individual case at twelfth week of
      injection was 4.1 +/- 1.1 nmol/l. In conclusion, trabecular bone density in long
      term DMPA users were not statistically different from normal menstruating women
      who have not received injectable DMPA.

PMID- 7811193
TI  - Successful pregnancy after heart-lung transplantation: a case report.
AB  - A successful pregnancy outcome in a patient with previous heart-lung
      transplantation is reported. A 22-year-old primigravid woman received heart-lung
      transplantation for Eisenmenger's ASD and conceived 22 months postoperatively.
      She had been continuously treated with cyclosporine, azathioprine and prednisone
      during pregnancy. Her antenatal course was uneventful. At 39 weeks' gestation,
      she developed leakage of amniotic fluid and went into spontaneous labor. She
      vaginally delivered a 2,550 g male infant by elective forceps extraction, with
      Apgar scores of 8 and 9 at 1 and 5 minutes, respectively. Mother and baby had an
      uneventful postpartum course.

PMID- 7811194
TI  - Ultrasound diagnosis of rudimentary uterine horn pregnancy in fourteen weeks of
      gestation: a case report.
AB  - Pregnancy in a rudimentary uterine horn is rare. Rupture tends to occur in the
      second trimester, and results in maternal morbility and mortality. Although the
      diagnosis prior to rupture is difficult, early detection is essential in avoiding
      a fatal outcome. An asymptomatic case of pregnancy in the rudimentary horn of a
      bicornuate uterus prior to rupture is presented. This report is to emphasize the
      important value of sonography for early detection of the prerupture of the
      rudimentary pregnancy.

PMID- 7811195
TI  - Sudden death due to pulmonary tumor embolism in a patient with endodermal sinus
      tumor of the ovary.
AB  - Only 2 cases of fatal pulmonary tumor embolism have been described in patients
      having malignant tumors of the ovary. Both were diffuse microtumor emboli in the
      pulmonary arteries of elderly individuals. We present a teen-aged patient who
      died suddenly due to a massive tumor embolism of the right main pulmonary artery
      after a two-year remission of an endodermal sinus tumor of the ovary. Upon her
      first admission, she was treated with radical operation and insufficient
      chemotherapy. Two years later, she was readmitted to our hospital because of the
      sudden onset of dyspnea and shock; and she died 5 hours after readmission. A case
      of endodermal sinus tumor of the ovary with fatal pulmonary tumor embolism is
      described.

PMID- 7811196
TI  - A prospective study of the treatment of cervical intraepithelial neoplasia by
      loop electrosurgical excision procedure (LEEP) in Hong Kong population.
AB  - From May to December 1990, 72 patients suffering from cervical intraepithelial
      neoplasia confirmed with guided biopsy were treated with loop electrosurgical
      excision procedure (LEEP) as outpatients under local anaesthesia. Overall success
      rate of a single treatment at 6 weeks follow-up was 88.9%. All the specimens
      obtained from the procedure were of good quality for histological examination.
      The overall significant complication rate of the procedure was 4.2% during
      treatment and 8.4% after treatment. The results suggested that LEEP is an
      effective and safe outpatient treatment for CIN lesions. It is easy to use and
      readily acceptable to patients. It also has the advantage of providing
      histological confirmation and more economical than the use of laser.

PMID- 7811197
TI  - The influence of obstetric workload on cesarean section rate.
AB  - The cesarean section rate in a busy obstetric unit was studied in relation to the
      monthly confinement rate. A total of 30,825 births over a period of 5 years were
      analyzed. There was a negative correlation between the emergency cesarean section
      rate and the unit workload (correlation = -.498, 2 tailed p = 0.0001) whilst
      there was no relationship between workload and the elective cesarean section
      rate. This suggested that the unit may reach a certain saturation level as far as
      the emergency cases were concerned during the busy periods. However, there was no
      evidence that the perinatal outcome was affected by this variation in emergency
      cesarean section rate.

PMID- 7811198
TI  - Maternal mortality: evolving trends.
AB  - Despite improvement in socioeconomic standards, good and accessible health care
      facilities the maternal mortality rate in Singapore is not declining. The
      maternal mortality rate in National University Hospital, Singapore, over a 7 year
      period 1986-1992 was 22.9 per 100,000 when direct and indirect causes were
      considered (34.4 per 100,000 when incidental deaths were included). However
      closer scrutiny reveals that most deaths were not due to the traditional direct
      causes of haemorrhage, sepsis, embolism or hypertensive disease. Most were due to
      medical disorders which in their own right carries a high risk to life even
      without a pregnancy.

PMID- 7811199
TI  - A comparison of enzyme-linked immunosorbent assay (ELISA) with sperm
      immobilization test (SIT) in detection of antisperm antibodies in sera of
      infertile women.
AB  - In the present study, an enzyme-linked immunosorbent assay (ELISA) for antisperm
      antibodies was compared with a traditional standard sperm immobilization test
      (SIT) in sera from 158 infertile women in order to evaluate their clinical
      usefulness for various causes of infertility. Ten pregnant and unmarried women
      were used as the control group. There was a higher incidence rate by ELISA
      (13.9%) compared with that by SIT (10.1%) after examination of overall samples,
      although the difference was not statistically significant. The unexplained
      infertility group exhibited the highest incidence among the various causes of
      infertility in both of these two methods. Fifteen (93.8%) of 16 patients with
      positive SIT showed positive reaction in ELISA method, indicating that a close
      correlation exists between the two methods. The positive predictive value (54.5%)
      of ELISA was significantly (p < 0.05) lower than that (87.5%) of SIT, as
      evaluated with the results of postcoital test (PCT) performed at periovulatory
      phase. This suggests that the ELISA method for antisperm antibodies is less
      specific than SIT in view of the PCT results. Nevertheless, no fresh sperms are
      not required for the ELISA examination. Thus, it seems that the ELISA method may
      provide a convenient and practical means for mass screening in detecting
      antisperm antibodies in clinical practice.

PMID- 7811201
TI  - Oral mucosal ulceration due to cytomegalovirus associated with human
      immunodeficiency virus infection. Case report and brief review.
AB  - Reports of oral lesions associated with cytomegalovirus (CMV) infection in human
      immunodeficiency virus (HIV) infected patients are uncommon. In this article a
      case of CMV infection associated with oral mucosal ulceration and a brief review
      of the subject is presented. Establishing the cause of ulceration is important in
      determining a definitive diagnosis and prescribing appropriate therapy. It is
      important to recognize that CMV associated oral mucosal ulceration may be the
      initial manifestation of human immunodeficiency virus (HIV) infection.

PMID- 7811200
TI  - Prolactin response to suckling in a group of fully breast feeding women during
      the early postpartum period.
AB  - Prolactin response to suckling was studied in a group of fully breast feeding
      women (N = 58) between 4-6 weeks postpartum. Basal, suckling stimulated and the
      increment of prolactin showed wide individual variations. Basal prolactin
      concentrations varied from 140 to 4,600 mIU/l, suckling stimulated prolactin from
      400 to 5,600 mIU/l and the increment of prolactin from 40 to 4,160 mIU/l. Basal
      (p = 0.0395) and suckling stimulated (p = 0.0423) prolactin concentrations
      significantly increased as the number of night breast feeds increased and the
      suckling stimulated (p = 0.0218) prolactin concentrations significantly increased
      as the number of breast feeds/24 h increased. However, the magnitude of the rise
      in prolactin in response to suckling was not dependent on basal prolactin
      concentration. Basal, suckling stimulated or the increment of prolactin were not
      significantly different between subjects having different breast feeding
      frequencies, when the subjects were grouped according to the number of breast
      feeds. These differences may be due to the large individual variation in
      prolactin concentrations seen in women having similar breast feeding frequencies
      which may arise from individual variations in hypothalamic--pituitary response to
      suckling.

PMID- 7811202
TI  - An infected mandibular fracture. Case report.
AB  - A case of an infected mandibular fracture is presented. A submandibular abscess
      appeared to arise from chronic pericoronal infection associated with a third
      molar tooth in the line of fracture. Treatment of the case is described followed
      by a short discussion on the aetiology and management of infected mandibular
      fractures. The importance of adequate first aid and prompt referral is stressed.

PMID- 7811203
TI  - Iatrogenic bismuth poisoning. Case report.
AB  - A case of bismuth intoxication following the intraoral use of BIPP-impregnated
      gauze packs is presented. This report illustrates the need for caution when using
      potentially toxic compounds in the oral cavity where significant quantities can
      be absorbed to produce symptoms of poisoning.

PMID- 7811204
TI  - Alterations in blood pressure and pulse rate in exodontia patients.
AB  - The measurement of blood pressure and pulse rate prior to, during and after
      exodontia was conducted on 60 healthy patients. The aims were to first,
      investigate the changes in blood pressure and pulse rate, and second, to observe
      the presence of any clinically significant change over time. Thirty patients
      attending an Oral Medicine Clinic were used as the control group to allow a
      comparison to be made between the effects of exodontia and non-invasive
      treatment. The results suggested that exodontia was the most stressful part of
      the procedure. Bradycardia during local analgesia was also noted. These changes
      in the cardiovascular parameters may represent a risk to patients with heart
      diseases especially those previously undiagnosed. Further, the results indicate
      the effect stress can have on the cardiovascular system and the importance of
      eliminating pain and minimizing patient anxiety.

PMID- 7811205
TI  - Familial hemifacial microsomia due to autosomal dominant inheritance. Case
      reports.
AB  - Hemifacial microsomia is a rare dentofacial anomaly which is regarded as a
      separate entity to Goldenhar syndrome and primarily affects the structures of the
      first branchial arch. It has a heterogeneous aetiology and tends to occur
      sporadically, though positive family histories have been reported. This paper
      reports on individuals in two generations of a family that has overlapping
      features of hemifacial microsomia and Goldenhar syndrome segregating as an
      autosomal dominant condition.

PMID- 7811207
TI  - Mechanical properties of some polymer materials used for tooth positioners.
AB  - The chemical composition, thermal behaviour and mechanical properties of three
      tooth positioner materials, Urethane P1 (P1), White Rubber (WR) and Elastocryl
      (EL) were investigated. Infra-red spectrophotometry indicated the P1 polyurethane
      material to be of the polyether type, and EL to be a blend of poly(ethyl
      methacrylate) and poly(methyl methacrylate) while WR appeared to be filled cis
      poly (isoprene) (natural rubber). The glass transition temperature (Tg) for EL
      was determined as approximately 10 degrees C, and for both P1 and WR the Tg was
      less than -50 degrees C. The stress relaxation behaviour was assessed in
      compression by measuring the stress variation with time. The results for all
      three materials conformed to the superelastic theory of rubber elasticity. EL
      exhibited both a more rapid rate and higher degree of stress relaxation than did
      P1 and WR. Recovery from deformation was assessed by compressing cylinders for
      given periods of time and then measuring the level of reduced residual strain of
      the material with time. All three materials exhibited significant residual strain
      (epsilon(t)) over 'clinically relevant' time periods, and the reduced residual
      strain (epsilon(t)/epsilon(O)) following deformation was greater for EL than P1
      or WR. There was some indication that the three materials have some permanent set
      following deformation. It was concluded that, in considering desirable mechanical
      properties of tooth positioner materials, EL is the least suitable of the three
      examined, with none of the materials being ideal.

PMID- 7811206
TI  - Shear bond strength of a resin composite to enamel etched with maleic or
      phosphoric acid.
AB  - The purpose of this study was to evaluate the effect of 10 per cent maleic and 37
      per cent phosphoric acid on the shear bond strength of Z100 composite resin with
      Scotchbond Multi-Purpose adhesive to primary and permanent tooth enamel. Four
      groups of 20 teeth each were established: 1, permanent teeth, 10 per cent maleic
      acid etched for 15 seconds; 2, permanent teeth, 10 per cent maleic acid etched
      for 30 seconds; 3, permanent teeth, 37 per cent phosphoric acid etched for 15
      seconds; 4, primary teeth, 10 per cent maleic acid etched for 15 seconds. Five
      teeth from each group were randomly assigned for SEM examination of the etched
      enamel surface. Scotchbond Multi-Purpose primer and adhesive were applied to the
      etched enamel surface of the remaining 15 teeth and cured following the
      manufacturer's instructions. Z100 composite resin was placed in a nylon cylinder
      and cured for two 40 second intervals. Following thermocycling, the specimens
      were sheared on an universal testing machine and debonded areas were examined
      visually with a stereo microscope and with SEM. The mean shear bond strengths in
      MPa were: 1, 17.00; 2, 14.58; 3, 14.66; 4, 11.18. ANOVA and Student-Newman-Keuls
      analyses revealed no statistically significant difference among the groups. SEM
      examination showed the majority of specimens fractured at the adhesive-resin
      interface.

PMID- 7811208
TI  - Plane of occlusion--a new concept.
AB  - A new concept of the plane of occlusion based on anatomical landmarks has been
      developed. The posterior end of the plane is set by the centres of the retromolar
      pads, and the anterior end of the plane is at the upper lip line. These three
      points establish the plane of occlusion. An articulator has been developed to use
      this concept, which has been found to be clinically satisfactory for the
      construction of complete dentures.

PMID- 7811209
TI  - Physiopathology of primary periodontitis associated with plaque. Microbial and
      host factors. A review. Part 2.
AB  - To a considerable extent, host factors condition the initiation and progression
      of periodontitis. The integrity of the periodontal structures and the immune
      elements in the gingival fluid may act as a defensive barrier against
      microorganisms. However, immune over-response may lead to tissue damage and bone
      resorption from anaphylactic reactions, immunocomplex reactions, type IV
      hypersensitivity, complement hyperactivation via the alternative pathway, or
      direct action of leukocytes and macrophages. Moreover, insufficient host response
      allows bacteria to escape control, allowing more rapid progression of the
      disease.

PMID- 7811210
TI  - Service-mix provided to patients in Australian private practice.
AB  - Service-mix can reflect changes in demographic factors, oral health, patient
      demand and treatment philosophies. The aim of this study was to compare service
      mix by patient age in 1988 with baseline data from 1983. A weighted, stratified
      random sample of dentists in Australia was surveyed by mailed questionnaire in
      1983 and again in 1988. Service-mix was dominated by restorative, diagnostic and
      preventive areas. Comparing 1988 with 1983, there were significant increases for
      diagnostic, preventive, advanced restorative, orthodontic and general areas.
      Patterns across patient age groups and between years indicated younger patients
      were being provided with increased preventive services (patients aged 5-11, 25-44
      years) and decreased restorative services (patients aged 5-11, 12-17 years),
      while older patients were being provided with reduced prosthodontic services
      (patients aged 25-44, 45-64 years), but increased restorative services (patients
      aged 45-64, 65+ years) and advanced restorative services (patients aged 25-44, 45
      64 years). These patterns of service-mix have implications for dental education,
      research and service delivery.

PMID- 7811211
TI  - Dental informatics for Australia.
AB  - Dentistry is undergoing significant changes with need for the dentist to manage a
      larger body of knowledge and information. There will be increasing reliance on
      electronic information systems in education, research, and dental practice.
      Dental informatics is concerned with computer and information science and
      technology and communications. Goals, that could be adopted for Australia, were
      proposed in the USA in 1989. Specific action steps that could meet those goals
      are proposed for Australia.

PMID- 7811212
TI  - Attitudes and smoking habits of dentists in Victoria: 16 years on.
AB  - In 1977 a survey of Victorian dentists measured their smoking prevalence, and
      their attitudes to dealing with patients who smoked. In 1993 these questions were
      repeated as part of a telephone survey of Victorian dentists. From 1977 to 1993
      their prevalence of daily smoking had dropped from 30 per cent to 6 per cent, and
      this was not attributable simply to an influx of younger dentists who had never
      smoked. Many of those who had graduated in 1977 or more recently had never
      smoked, but many of the earlier graduates had quit, and there was no difference
      in the current smoking prevalence of the two groups. There had also been a change
      in dentists' attitudes towards smoking patients, with more of the 1993 sample (55
      per cent) than the 1977 sample (43 per cent) agreeing with the statement 'I
      encourage all my patients to give up smoking wherever possible'. Again, the more
      experienced dentists were adopting the new behaviours, not just the more recent
      graduates. Even so, in 1993 nearly half the dentists waited until the patient
      either was affected by smoking, or asked for advice before raising the issue.

PMID- 7811213
TI  - Dentistry again in the headlines.

PMID- 7811214
TI  - Prophylaxis for infective endocarditis.

PMID- 7811215
TI  - Attitudes of the elderly towards their own oral health and dentistry.

PMID- 7811216
TI  - HIV infection and the dentist ... costs.

PMID- 7811217
TI  - Cognitive-behavioral management of motion sickness.
AB  - This monograph is intended to provide health professionals with information on a
      cognitive-behavioral technique which was developed to teach individuals who are
      prone to motion sickness to better cope with motion environments. It includes an
      overview of motion sickness, describing the signs and symptoms, etiology and
      incidence of this malady. Prevention and treatment are then reviewed, including
      both pharmacological and non-pharmacological therapies. The historical background
      on the cognitive-behavioral technique is then discussed. This is followed by a
      review of supporting experimental work, and an account of how such counselling
      should be carried out. Finally, a number of current military desensitization
      programs are compared and contrasted with cognitive-behavioral therapy.

PMID- 7811218
TI  - Aetiology and pathogenesis of hormonal and metabolic disorders in HIV infection.
AB  - Many hormonal and metabolic disturbances are documented in HIV infection, the
      most important of which is the wasting syndrome associated with progressive HIV
      infection. We are only now beginning to understand the pathogenesis of these
      disturbances. In rare cases, infiltration of endocrine tissue by secondary
      infectious or malignant processes is the underlying cause of hormonal
      insufficiency. In most instances, however, hypofunction is secondary to the well
      known effects of severe illness. Similarly, hyperfunction of the adrenal axis
      along with many of the derangements in substrate metabolism are also likely to be
      secondary to severe illness, perhaps through activation of cytokines and other
      molecules. Specific disturbances in asymptomatic patients are more difficult to
      document and may represent unique and as yet unexplained manifestations of HIV
      disease. Hypermetabolism and depletion of lean body mass are most profound in the
      acutely ill patient with active secondary infection. At this stage, the HIV
      infected patient is in a catabolic state and adaptive mechanisms which normally
      decrease energy expenditure and preserve lean body mass are either overridden or
      not operative. Strategies to reverse the catabolic state and diminish wasting are
      only now being developed.

PMID- 7811219
TI  - Hypothalamic and pituitary function in AIDS.
AB  - Clinically relevant HP dysfunction occurs infrequently in the course of HIV
      infection and AIDS, and is usually due to destruction or infiltration of the
      region by opportunistic infections. However, more subtle defects occur with much
      greater frequency. Since these impairments, especially in the gonadotrophic and
      corticotrophic axes, are observed in HIV patients before the development of ARC
      or AIDS, direct involvement of the hypothalamus or pituitary by the neurotropic
      HIV virus or by other HIV-mediated factors is possible. Further investigation of
      hypothalamic and pituitary hormones by provocative means, in addition to
      assessment of the pulsatile secretion of these hormones, at all stages of HIV
      infection will be needed to clarify the role of the virus in these individuals.

PMID- 7811220
TI  - Adrenal complications of HIV infection.

PMID- 7811221
TI  - The syndrome of acquired glucocorticoid resistance in HIV infection.
AB  - A certain number of HIV-infected patients (about 17% in our series) manifest
      symptoms of cortisol resistance--weakness, weight loss, hypertension, chronic
      fatigue and intense mucocutaneous melanosis--symptoms which are also typical of
      Addison's disease. The diagnosis of cortisol resistance is determined through the
      increased plasma and urinary cortisol values and limited increases in ACTH
      values. Compared with patients with primary glucocorticoid resistance, AIDS
      patients have no symptoms of mineral-corticoid or androgen excess, only of
      glucocorticoid deficiency at target tissues. Mononuclear leukocytes from these
      patients show receptor changes which consist of an increased receptor number and
      decreased receptor affinity for glucocorticoids. They also show defective
      glucocorticoid-induced inhibition of [3H]thymidine incorporation. Glucocorticoid
      resistant AIDS patients have a characteristic persistent increase in interferon
      alpha production. The inverse correlation between plasma values of interferon
      alpha and the receptor affinity for glucocorticoids clearly suggests that
      interferon production is regulated by the glucocorticoid receptor: the smaller
      the glucocorticoid effect on lymphocyte cells is, the greater interferon
      production is. Owing to the antiviral effect of interferon-alpha, it is possible
      that glucocorticoid-resistant AIDS patients have greater defences against viral
      infection than other AIDS patients. As interferon-alpha is melanogenetic, its
      increased production may also explain the intense skin pigmentation found in
      patients with the glucocorticoid-resistance syndrome.

PMID- 7811222
TI  - Glucocorticoids and the immune system in AIDS.
AB  - Data reported in the literature show in the majority of cases an increased basal
      cortisol level in HIV-positive patients compared with controls, although the
      plasma concentration of cortisol in HIV-positive patients is generally within the
      physiological range. It is well known that pharmacological doses of
      glucocorticoids are immunosuppressive, but little is known about the effects of
      physiological concentrations of cortisol on the immune system. If a dialogue
      really exists between the HPA axis and the immune system, immune responses should
      be modulated by physiological concentrations of cortisol, as well as pathological
      levels of cortisol (high as in Cushing's syndrome or low as in Addison's
      disease), which are known to be associated with impaired immune system responses.
      We suggest that in HIV-positive patients, a chronic increase in the basal
      endogenous cortisol levels may provoke an imbalance in cytokine production, with
      a decrease in the production of type 1 and an increase in that of type 2. The
      type 1 to type 2 shift might be synergic with the increased cortisol levels in
      enhancing viral replication and apoptotic phenomena, and finally in causing the
      progression of HIV infection.

PMID- 7811223
TI  - Steroid hormone, cytokine, lipid and metabolic disturbances in HIV infection.

PMID- 7811224
TI  - Thyroid dysfunction in HIV infection.
AB  - During infection with HIV, overt clinical or biochemical thyroid dysfunctions are
      rare. When present, thyroid failure generally results from the destruction of the
      thyroid gland by opportunistic infections such as Pneumocystis carinii, or
      tumoural processes such as KS. Less frequently, hypothalamic-pituitary failure
      due to central nervous system infections is involved. Some cases of thyroiditis
      with thyrotoxicosis or hypothyroidism due to Pneumocystis carinii have also been
      reported. Subtle alterations of thyroid function tests are more common in HIV
      infection and are sometimes already detectable in the early phase of the disease.
      Contrary to what is observed in severe non-thyroidal illnesses, the low T3
      syndrome and the sick euthyroid syndrome are less marked; these changes are
      mainly present in the final stage of the disease, when anorexia and weight loss
      occur, and indicate a poor outcome. Unique abnormalities of thyroid function
      indices have also been recently documented. A progressive elevation in serum TBG-
      but not in other binding proteins such as CBG and SHBG--accompanying the decline
      of the CD4 lymphocyte count, and associated with a concomitant increase in the
      serum T4 value, has been reported. An unusual prolonged maintenance of normal T3
      levels with a paradoxical decrease in serum rT3 values has also been recognized.
      Finally, a hypothyroid-like regulation of the pituitary-thyroid axis, possibly
      directed to limit hypermetabolism in HIV infection, has been observed. The
      recognition of these particular thyroid profiles is of clinical importance as
      serum TBG appears to be a specific marker of the progression of HIV infection and
      serum T3 a reliable prognostic indicator for AIDS.

PMID- 7811225
TI  - Hyponatraemia in AIDS.
AB  - Hyponatraemia is very common in AIDS patients. It is observed in about 40-50% of
      hospitalized patients. It may contribute to overall mortality in advanced
      disease. Vasopressin measurements in these patients basically present two
      distinct syndromes: hyponatraemia and 'normal' vasopressin levels (i.e.
      measurable vasopressin) and hyponatraemia with suppressed vasopressin.
      Hyponatraemia with suppressed vasopressin is very rare and has only been observed
      in AIDS patients with dementia and primary polydipsia. Hyponatraemia and
      measurable vasopressin can be also divided into two syndromes. In some patients
      vasopressin is 'appropriately' elevated, i.e. in those with body fluid losses
      (diarrhoea) or chronic hypovolaemia (adrenal failure); these patients also
      present with hyperuricaemia and other signs of low blood volume. In other
      patients vasopressin is 'inappropriately' elevated in those with no clinical
      evidence of hypovolaemia (typically characterized by low serum uric acid levels)
      such as in Pneumocystis carinii pneumonia and other opportunistic infections
      leading to SIADH. CSWS is a relatively frequent complication in some patients
      with cerebral infection or tumour. High-dose trimethoprim (for Pneumocystis
      carinii prevention) acts as an amiloride-like drug and induces a clinical state
      characterized by hyponatraemia and hyperkalaemia which is indistinguishable from
      hyporeninaemic hypoaldosteronism. The mechanism of the hyponatraemia caused by
      other drugs (miconazole, pentamidine, amphotericin, vidarabine) is not as yet
      known.

PMID- 7811226
TI  - Gonadal function in AIDS.

PMID- 7811227
TI  - Pancreatic lesions in HIV-infected patients.
AB  - The pancreas is frequently involved during HIV infection, especially by
      disseminated infections or neoplasms. These lesions are generally asymptomatic
      and are discovered at autopsy. However, hypoglycaemia secondary to massive
      pancreatic infiltration by a tumour or tuberculous necrosis may occur. The most
      important cause of pancreatic dysfunction in HIV-infected patients is a drug
      toxic effect (intravenous pentamidine, didanosine, zalcitabine). Hypoglycaemia,
      which may or may not be followed by diabetes, can develop during intravenous
      pentamidine therapy. In cases with increased serum amylase and/or lipase levels,
      potentially toxic drugs must be promptly discontinued to avoid major pancreatic
      involvement.

PMID- 7811228
TI  - The extrinsic proteins of photosystem II in photosynthetic organisms:
      distribution, properties and evolutionary implications.
AB  - Photosystem II from higher plant chloroplasts contains extrinsic proteins of
      molecular weights 33, 23 and 16 kDa. Cyanobacteria, which are thought to be
      closely related to the evolutionary progenitor of chloroplasts, have a protein
      homologous to the largest of these, but lack homologues of the smaller ones. Here
      we report immunological evidence for the occurrence of the 33 kDa extrinsic
      protein in red and chromophyte algae and its absence from anoxygenic
      photosynthetic bacteria. The 23 kDa protein was absent from all three groups. The
      red algal protein was found to be hydrophilic and rather more loosely associated
      with the thylakoid membrane than its higher plant equivalent. These findings
      support an origin for all plastids among the oxygenic prokaryotes, in contrast to
      the phylogeny inferred from ribulose bisphosphate carboxylase-oxygenase sequence
      data.

PMID- 7811229
TI  - Identification and characterization of a sperm peptide antigen recognized by a
      monoclonal antisperm autoantibody derived from a vasectomized mouse.
AB  - A monoclonal autoantibody (MAb) to mouse sperm was established from a
      vasectomized mouse. The MAb, termed 4A11, reacted exclusively to mouse and rat
      live sperm tail, without any cross-reaction with sperm of other mammalian species
      or any somatic organ tissues in the mouse. MAb 4A11 significantly inhibited in
      vitro fertilization of mouse ova. Western blotting showed a single band of 67 kDa
      as the corresponding antigen protein of MAb 4A11. By screening a mouse testis
      cDNA library with MAb 4A11, one positive clone (964bp) was obtained. DNA sequence
      of the clone showed no homology with any previously reported mammalian genes, but
      showed 54% homology with a bacterial gene of sucrose-specific phosphotransferase
      enzyme II. The rabbit antisera raised to the recombinant protein of the 4A11 cDNA
      gene showed reaction to mouse, rat, hamster and guinea-pig sperm.

PMID- 7811230
TI  - Vitamin A regulates the expression of apolipoprotein AI and CIII genes in the
      rat.
AB  - The effect of vitamin A on the expression of apoAI and CIII genes in intact rats
      was studied. In vitamin A-deficient rats, the hepatic level of apoAI mRNA was
      increased and enhanced by an oral administration of excess retinoic acid(RA). A
      similar administration to normal rats caused an increase in the apoAI mRNA level
      in the intestine without affecting that of hepatic mRNA. Though the hepatic level
      of apo CIII mRNA was not affected by the vitamin A status, the intestinal level
      was positively regulated by vitamin A. These findings show that vitamin A
      regulates the expression of apolipoprotein AI and CIII genes in a tissue-specific
      and complex fashion.

PMID- 7811231
TI  - The transcription factor Sp1 is required for induction of the murine GM-CSF
      promoter in T cells.
AB  - The cis-acting region, GM-kappa B/GC-box (positions -95 and -73), within the
      murine GM-CSF gene promoter is required for maximal induction by stimulation with
      phorbol-12-myristate acetate (PMA) and calcium ionophore (A23187) in T cells. GM
      kappa B defines a binding site for NF-kappa B, and GC-box defines a binding site
      for three (A1, A2, B) constitutive proteins. We report here that three copies of
      the GC-box can functionally compensate for the GM-kappa B/GC-box region,
      suggesting that the GC-motif can function independently of the GM-kappa B motif.
      The major GC-box binding activity A1 was purified and identified as the
      transcription factor Sp1. We show that depletion of Sp1 (A1) from nuclear
      extracts specifically decreases in vitro transcription activity on GM-CSF
      templates. Since the human GM-CSF promoter has a base difference within the GC
      box, we speculate that this may explain why the human promoter is weak and that
      an upstream enhancer is required for the induction of the human GM-CSF gene.

PMID- 7811232
TI  - Alternative splicing of the ret proto-oncogene at intron 4.
AB  - Using reverse-transcription polymerase chain reaction (RT-PCR), we identified
      three alternative splicing pathways of the ret proto-oncogene (proto-ret) which
      occur at intron 4. Although the majority of the primary transcripts were spliced
      to make mRNA encoding the protein product previously reported, two alternatively
      spliced transcripts containing either a 62 bp or a 69 bp insertion were also
      present. Intron 4 of proto-ret was cloned from human genomic DNA using a PCR
      method, and both the 62 bp and 69 bp sequences were localized in the intron.
      Furthermore, using a semi-quantitative RT-PCR method, we found that the
      expression of the two alternatively spliced transcripts varies in cell lines
      derived from different tissues. The relative amount of the transcripts containing
      the 62 bp insertion in these cell lines was: THP-1 > NB-39-nu = TT, whereas the
      relative amount of the transcripts containing the 69 bp insertion was: THP-1 > TT
      > NB-39-nu.

PMID- 7811233
TI  - Alterations of binding mode and cutting site by G-->I replacement in preferred
      cleavage sequences 5'-AGG of chromoprotein C-1027.
AB  - Replacement of guanosine by inosine at the center position of a target
      trinucleotide 5'-AGG resulted in greatly diminished DNA cleavage by C-1027
      chromophore, indicating that the guanine 2-amino group significantly participates
      to DNA binding and cleavage by the chromophore of C-1027. This notion was
      supported by fluorescence titrations of the chromophore with [poly(dG-dC)]2 and
      [poly(dI-dC)]2. In preferred cleavage sequence 5'-AGG of the enediyne chromophore
      of C-1027, the G-->I substitution clearly induces change of DNA binding mode and
      cutting site.

PMID- 7811234
TI  - S-adenosyl-L-homocysteine hydrolase from Xenopus laevis--identification,
      developmental expression and evolution.
AB  - S-Adenosyl-L-homocysteine hydrolase (EC 3.3.1.1) is an important enzyme in the
      trans-sulphuration pathway, mediating the conversion of S-adenosyl-L-homocysteine
      to adenosine and L-homocysteine. We have identified a cDNA clone from Xenopus
      laevis, encoding a protein of 433 aa, which is highly conserved with S-Adenosyl-L
      homocysteine hydrolases (Adohcyases) from other species. Expression of Adohcyase
      mRNA in X.laevis tadpoles is detectable from developmental Stage 27 onwards.
      Phylogenetic analysis of available Adohcyase sequences indicates that species
      cluster essentially as predicted from morphological data. Furthermore, we
      estimate that S-adenosyl-L-homocysteine hydrolase is evolving very slowly, almost
      10 times slower than the average rate.

PMID- 7811235
TI  - Persistent expression of proto-oncogene c-fos stimulates osteoclast
      differentiation.
AB  - We analyzed c-fos mRNA expression by northern blotting analysis in chicken
      osteoclast precursors which spontaneously differentiate to multinucleated
      osteoclasts in 5-6 days. Osteoclast precursors as well as mature multinucleated
      osteoclasts showed constitutive expression of c-fos mRNA which is not found in
      osteoblasts. The c-fos expression was enhanced transiently by serum, dibutyryl
      cAMP (10(-4) M) and phorbol 12-myristate 13-acetate (TPA) (5 x 10(-7) M). To
      clarify the role of c-fos in osteoclast differentiation, c-fos DNA was
      transfected into osteoclast precursors. Greater than 2 fold increases in tartrate
      resistant acid phosphatase (TRAP) and bone resorptive activity were observed in
      the transfected cells compared to controls 3 days after transfection, suggesting
      that prolonged expression of c-fos caused enhanced osteoclast differentiation.

PMID- 7811236
TI  - Hamster gastric inhibitory polypeptide receptor expressed in pancreatic islets
      and clonal insulin-secreting cells: its structure and functional properties.
AB  - We have isolated a cDNA encoding a gastric inhibitory polypeptide (GIP) receptor
      from a hamster insulinoma (HIT-T15) cDNA library. The hamster GIP receptor is a
      462 amino acid protein having seven transmembrane segments. Expression of
      recombinant of hamster GIP receptors in Chinese hamster ovary (CHO) cells shows
      that it binds specifically to GIP with high affinity (IC50 = 9.6 nM) and is
      positively coupled to adenylate cyclase, but not to phospholipase C. RNA blot
      analysis reveals that a 3.8-kb GIP receptor mRNA is expressed at high levels in
      rat pancreatic islets as well as in HIT-T15 cells.

PMID- 7811237
TI  - D-myo-inositol 1,4,5-trisphosphate binding domain of phospholipase C-delta 1.
AB  - D-myo-Inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) binding domain of phospholipase
      C-delta 1 (PLC-delta 1) was determined by examining binding activity of the
      synthetic peptide corresponding to residues 30-43 of PLC-delta 1. The peptide
      coupled with carrier proteins such as keyhole limpet hemocyanin or bovine serum
      albumin bound Ins(1,4,5)P3, whereas a scrambled peptide with the same amino acids
      did not do so. Polyclonal antibody against the peptide was examined to determine
      whether it would cause inhibition of the Ins(1,4,5)P3 binding to PLC-delta 1. Fab
      fragment of antibody to the peptide did inhibit binding to PLC-delta 1, in a dose
      dependent manner. Thus it seems likely that the region of residues 30-43 of PLC
      delta 1 is responsible for the binding of Ins(1,4,5)P3.

PMID- 7811239
TI  - Identification of the non-specific lipid-transfer protein (sterol carrier protein
      2) in peroxisomes of lung type II cells.
AB  - In view of the proposed role of the non-specific lipid-transfer protein (nsL-TP;
      sterol carrier protein 2) in the metabolism of pulmonary surfactant lipids
      (Batenburg et al. (1994) Biochem. J. 298, 223-229), its subcellular localization
      was studied in the surfactant producing alveolar type II cells. It was shown by
      immuno-electron microscopy that nsL-TP colocalizes with the peroxisomal marker
      catalase. The peroxisomal localization of nsL-TP was confirmed by gradient
      fractionation of type II cell homogenates. As a peroxisomal marker acyl
      CoA:dihydroxyacetone-phosphate acyltransferase was assayed. Given this
      subcellular localization, it is very unlikely that nsL-TP plays a role in the
      transfer of surfactant lipids from the endoplasmic reticulum to the lamellar
      bodies. These results strengthen the opinion that peroxisomes are involved in
      surfactant synthesis.

PMID- 7811238
TI  - On the induction of 5-lipoxygenase expression and activity in HL-60 cells:
      effects of vitamin D3, retinoic acid, DMSO and TGF beta.
AB  - Induction of 5-LO activity in DMSO differentiated HL-60 cells, by the serum
      protein TGF beta, was partially dependent on the presence of serum lipids
      (Steinhilber, D., Hoshiko, S., Grunewald, J., Radmark, O., and Samuelsson, B.
      (1993) Biochim. Biophys. Acta 1178, 1-8). Here we demonstrate that the serum
      lipid fraction can be substituted by picomolar concentrations of 1,25
      dihydroxyvitamin D3 (VD3). A high concentration of VD3 (24 nM) gave a 4-fold
      induction of 5-LO mRNA, a 14-fold increase in 5-LO protein, and a 38-fold
      upregulation of the 5-LO activity of intact HL-60 cells after differentiation in
      the presence of DMSO and serum proteins for 4 days. Also VD3 alone gave a
      substantial upregulation of 5-LO protein expression and activity. On the other
      hand, TGF beta alone was a poor inducer of the 5-LO pathway, the presence of a
      differentiation inducer (retinoic acid, DMSO or VD3) was required. The most
      prominent induction of 5-LO protein expression and activity in cell homogenates
      and intact cells was observed when VD3 and TGF beta were combined.

PMID- 7811240
TI  - Involvement of the alpha isoenzyme of protein kinase C in the growth inhibition
      induced by phorbol esters in MH1C1 hepatoma cells.
AB  - MH1C1 rat hepatoma cells express the alpha isoenzyme as the only phorbol-ester
      sensitive isoform of protein kinase C (PKC). In this cell line, phorbol 12
      myristate 13-acetate (PMA) induced a marked, dose-dependent growth inhibition.
      The administration of the PKC inhibitor staurosporine was able to mimic the
      effect of the phorbol ester on cell growth in a dose-dependent fashion, whereas
      the PKC activator arachidonic acid stimulated cell proliferation. Exposure of
      cells to an antisense oligonucleotide specific for alpha PKC caused a significant
      impairment of cell growth. These data suggest that the alpha PKC activity is
      required for proliferation of MH1C1 cells.

PMID- 7811241
TI  - Angiotensin converting enzyme inhibitor but not calcium blocker down-regulates
      gene expression of vascular natriuretic peptide receptor in hypertensive rats.
AB  - We have recently found that vascular natriuretic peptide (NP)-A receptor mRNA is
      upregulated in genetically hypertensive (SHR-SP/Izm) and deoxycorticosterone
      acetate (DOCA)-salt hypertensive rats. In the present study, we examined the
      effects of antihypertensive treatments on aortic NP-A receptor mRNA expression in
      these hypertensive rats using ribonuclease protection assay. Oral administration
      of an angiotensin converting enzyme inhibitor, derapril, but not a calcium
      channel blocker, manidipine, produced a significant decrease of the NP-A receptor
      mRNA level after 4 weeks, while both antihypertensive agents showed similar
      hypotensive effects. Plasma renin was high in SHR-SP/Izm and low in DOCA-salt
      rats. These results suggest that the vascular renin-angiotensin system rather
      than the blood pressure has an important role in the regulation of the vascular
      NP-A receptor.

PMID- 7811242
TI  - DNA topoisomerases I & II cleavage sites in the type 1 human immunodeficiency
      virus (HIV-1) DNA promoter region.
AB  - Topoisomerase sites were mapped in the 5'-long terminal repeat of HIV-1 DNA by
      agarose and sequencing gel electrophoresis. Topoisomerase II sites were observed
      in the absence and presence of teniposide and amsacrine in the transcription
      initiation region and the TATA box, consistent with a possible role of
      topoisomerase II in transcription. The NF-kB and Sp1 regions were poorly cleaved.
      Topoisomerase I sites were relatively unfrequent even in the presence of
      camptothecin. They were absent in the core promoter and were concentrated in the
      TAR and the upstream region near the junction with the host DNA.

PMID- 7811243
TI  - Role of the A/B region of the human mineralocorticoid receptor in aldosterone
      response selectivity.
AB  - In transfection experiments performed with wild-type MR, the maximal
      transcriptional activation of a mineralocorticoid response induced by
      glucocorticoid was generally similar to that of aldosterone, the natural
      mineralocorticoid hormone. However, compared to aldosterone, glucocorticoid
      activity decreased when the A/B region of MR was absent. We describe in this
      study the synthesis and biological activities of seven mutated MRs differently
      truncated in the N-terminal region. Using transient expression conditions in MCF
      7 cells, the N-terminal domain of MR has been shown to contain a region (residues
      254-390) whose deletion led to an apparent "aldosterone selectivity". These
      results suggest that this region could help to maintain the most
      transcriptionally active conformation of MR even in the presence of ligands which
      are not by themselves able to fully induce such a conformation.

PMID- 7811244
TI  - Molecular cloning and functional characterization of a human VIP receptor from
      SUP-T1 lymphoblasts.
AB  - We have cloned and sequenced a cDNA isolated from a human SUP-T1 lymphoblast cell
      line library. It encoded a 457 amino acids protein having 87% identity with the
      rat PACAP type II, VIP2 receptor. Chinese hamster ovary (CHO) cells stably
      transfected with cloned cDNA expressed a specific binding of 125I[Acetyl
      His1]PACAP-27. This binding was inhibited by GTP, and by the peptides helodermin,
      VIP, PACAP-27 and PACAP-38 that also stimulated adenylate cyclase activity. The
      order of potency was PACAP-38 > VIP > or = helodermin > or = PACAP-27. Comparison
      of the results in two cell lines expressing different receptor densities
      suggested that helodermin and PACAP-38 had a higher intrinsic activity than VIP
      and PACAP-27.

PMID- 7811245
TI  - Effects of thrombin and thrombin peptide activating receptor (SFLLRN) on
      proteoglycan synthesis and distribution in human endothelial cells.
AB  - In the present study we compared the effect of alpha-thrombin and the active
      receptor peptide (SFLLRN) on proteoglycan (PG) release from human endothelial
      cells (HUVEC) exposed for 24 h in the presence of 35S-sulfate and 3H-glucosamine.
      The effect of thrombin (5U/ml) and receptor peptide (100 microM) was evaluated on
      the distribution of PGs in the conditioned medium, cellular extract and
      extracellular matrix. In the conditioned medium, thrombin increased the amount of
      PGs. In extracellular matrix thrombin decreased radioactive PGs measured by both
      isotopes; no difference was observed in cell extracts. SFLLRN peptide showed a
      consistent increase in PG content in the medium. At variance with thrombin, in
      cell extracts the peptide increased the amount of PGs. No relevant differences
      were observed in PG content of extracellular matrix. These results indicate that
      thrombin and the peptide act differently on PG distribution and underline the
      different role of the serine protease and of the receptor binding activities of
      thrombin.

PMID- 7811246
TI  - Oxalate-induced initiation of DNA synthesis in LLC-PK1 cells, a line of renal
      epithelial cells.
AB  - These studies examined the effects of oxalate, a constituent of renal stones, on
      the growth of LLC-PK1 cells. Exposure to oxalate resulted in an initiation of DNA
      synthesis in serum-starved, growth-arrested cells as measured by 3H-thymidine
      incorporation. The effects of oxalate were comparable to those observed in
      response to 10% serum. Moreover, exposure to oxalate plus 10% serum stimulated
      DNA synthesis to a greater extent than oxalate or serum alone. These studies
      indicate that oxalate promotes the progression of cells from the G0/G1 to the S
      phase of the cell cycle. However, the increase in DNA synthesis was not always
      followed by an increase in cell number since high concentrations of oxalate led
      to a reduction in cell number.

PMID- 7811247
TI  - X-linked adrenoleukodystrophy (ALD): a novel mutation of the ALD gene in 6
      members of a family presenting with 5 different phenotypes.
AB  - Fragments of the adrenoleukodystrophy (ALD) cDNA from a patient with adolescent
      ALD were amplified by polymerase chain reaction and subcloned. Bidirectional
      sequencing of the entire coding ALD gene disclosed a cytosine to guanine
      transversion at nucleotide 1451 in exon five, resulting in substitution of
      proline 484 by arginine. Five of nine siblings of the patient, comprising two
      cerebral ALD, one adrenomyeloneuropathy, one Addison only as well as the
      symptomatic mother (all accumulating very long chain fatty acids) carried this
      mutation, which was not found in the unaffected persons, in five unrelated ALD
      patients, and in twenty controls. We propose that this missense mutation
      generated the disease per se as well as the metabolic defect; the different
      phenotypes, however, must have originated by means of additional pathogenetic
      factors.

PMID- 7811248
TI  - Novel bacterial P-type ATPases with histidine-rich heavy-metal-associated
      sequences.
AB  - Menkes disease and Wilson disease are human disorders of copper metabolism. It
      has recently been shown that both are due to mutations in P-type ATPase copper
      transport molecules. Related heavy metal transporting ATPases have been described
      in several strains of bacteria. In an effort to isolate other mammalian metal
      transporters, we screened a human small intestine library with probes homologous
      to conserved sequences in the known proteins. Two novel cDNAs were isolated,
      which encode new members of this family. Surprisingly, they were both of
      bacterial origin, most likely derived from E. coli sequences transduced during
      library construction.

PMID- 7811249
TI  - Construction of infectious molecular clones of HIV-1 containing defined mutations
      in the protease gene.
AB  - A DNA clone of HIV-1 containing the full-length infectious viral sequence was
      cleaved at a unique Nco I restriction site within the viral genome, and DNA
      fragments containing the 5' and 3' portions of the HIV genome were subcloned into
      separate plasmid vectors. The 5' 'half-virus' construct was further modified by
      incorporating a class IIS restriction site, Esp3I, near the 3' end of the
      protease gene of HIV. This site, in combination with a natural ApaI site near the
      5' end of the protease gene, creates a convenient cassette shuttle vector in
      which the protease coding region can be easily replaced. Recombinant viruses
      containing protease genes either altered by site-directed mutagenesis or
      amplified from clinical or laboratory isolates can be reconstructed. The DNA
      fragment containing the protease gene is first subcloned into the 5' half-virus
      shuttle vector plasmid. Infectious recombinant virus is subsequently recovered by
      cotransfecting 5' and 3' half-virus plasmids linearized at their common Nco I
      sites into mammalian cells. This method was successfully applied to constructing
      viruses containing various substitutions in protease.

PMID- 7811250
TI  - Rapid grouping of HIV-1 infection in subtypes A to E by V3 peptide serotyping and
      its relation to sequence analysis.
AB  - We developed a typing assay for HIV-1 using subtype specific peptides
      corresponding to the five major subtypes of HIV-1 (A to E). In eight patients
      serologically subtyped as A (n = 1), B (n = 3), C (n = 3) and E (n = 1)
      phyllogenetic analysis of sequenced V3 domain DNA completely correlated to the
      peptide serotyping. Out of 106 HIV-1 seropositive samples of a diverse
      geographical origin 88 (83%) could be subtyped by the peptide assay. Five were of
      subtype A, 33 of subtype B, 48 of subtype C, one of subtype D, and one was of
      subtype E. Swedish patients were mainly of HIV-1 subtype B and Ethiopian patients
      were mainly of subtype C, confirming the performance of the assay. Furthermore,
      subtype specific antibodies may persist up to nine years in HIV-1 infected
      patients though sera close to AIDS diagnosis may be difficult to type.

PMID- 7811251
TI  - Triplex formation at physiological pH by oligonucleotides incorporating 5-Me-dC
      (N4-spermine).
AB  - Oligonucleotide (ODN) directed triplex formation has therapeutic importance and
      depends on Hoogsteen hydrogen bonds between a duplex DNA and a third strand.
      While T*A:T triplets are formed at neutral pH, C+*G:C are favoured at acidic pH.
      Herein it is shown that 18-mer ODN containing spermine conjugated to 5-Me-dC at
      N4 (1-5), form triplexes with complementary 24-mer duplex 8:9 at neutral pH (7.3,
      100 mM NaCl). Under such conditions, control ODN's carrying dC (6) or 5-Me-dC (7)
      did not show any triple helix formation. Remarkably, the triplexes from spermine
      conjugates (1-5) have foremost stability at neutral pH (7.1), unlike the behavior
      of normal ODN's where optimal stability is at acidic pH (5.5). These results have
      importance in designing oligonucleotides for antigene applications.

PMID- 7811254
TI  - Evidence for the existence of vasopressin V2 receptor mRNA in rat hippocampus.
AB  - Arginine-vasopressin (AVP) in the septum and hippocampus are thought to be
      involved in memory and learning, and their receptors have been classified into
      three subtypes, V1a, V1b and V2. In this study, we tested for AVP V1a- and V2
      receptor mRNAs in the hippocampus of adult rats by a reverse transcription
      polymerase chain reaction (RT-PCR) method. PCR product of the V2 receptor mRNA
      was detected in the hippocampus, but that of V1a receptor mRNA was not. This is
      the first demonstration of the existence of the V2 receptor mRNA in the
      hippocampus.

PMID- 7811253
TI  - Ginsenoside-Rg1 regulates the induction of tyrosine aminotransferase gene
      transcription in rat hepatocyte cultures.
AB  - Ginsenosides present in the roots of Panax ginseng C.A. Meyer have been shown to
      induce a number of hepatocyte gene expression. We have recently demonstrated that
      ginsenoside-Rg1 (G-Rg1) stimulated the enzyme activity of tyrosine
      aminotransferase (TAT), a hepatocyte specific enzyme, of which enzyme activity
      was dose-dependently inhibited by RU486, a specific glucocorticoid antagonist.
      This study was therefore designed to determine whether G-Rg1 induces the
      transcriptional activity of TAT gene and to investigate whether G-Rg1 induces the
      gene transcription by glucocorticoid receptor- or cAMP-mediated induction
      mechanism. The slot blot hybridization analysis revealed that the TAT-mRNA level
      was increased by 9.3-fold in hepatocyte cultures in response to G-Rg1
      stimulation. In contrast, the inductive effect of G-Rg1 was almost equally
      inhibited, that is, by 49% or 50% respectively in the presence of RU486 or Rp
      cAMPs, a specific competitive inhibitor of protein kinase A. These results in
      hepatocyte cultures suggest that G-Rg1 modulates the TAT gene transcription
      through its influence on a functional or cooperative interaction between
      glucocorticoid receptor- and cAMP-mediated induction mechanism.

PMID- 7811252
TI  - Lovastatin induces growth inhibition and apoptosis in human malignant glioma
      cells.
AB  - The competitive HMG-CoA reductase inhibitor lovastatin has been shown to suppress
      growth and induce morphological changes in a variety of non-glioma tumor cell
      lines. This study assesses the effects of this agent on the growth and survival
      of the human malignant glioma cell lines A172 and U87-MG. The response to the
      drug was investigated using a cell proliferation assay which revealed significant
      dose-dependent growth inhibition. Treatment with as little as 100 nM lovastatin
      over a period of 72 hours led to DNA degradation into nucleosome-sized fragments
      characteristic of apoptosis. Our data suggest that HMG-CoA reductase inhibitors
      such as lovastatin merit further investigation as potential therapeutic agents
      for the treatment of malignant gliomas.

PMID- 7811256
TI  - Generation of free radicals from neocarzinostatin mediated by NADPH/cytochrome P
      450 reductase via activation of enediyne chromophore.
AB  - Neocarzinostatin (NCS) is one of the most potent antitumor agents. It contains a
      chromophore of a unique enediyne structure as its prosthetic group. Here, we
      report the generation of free radicals from NCS by the NADPH/cytochrome (cyt) P
      450 reductase system. Free radical species, which were generated in the reaction
      mixture of NCS/NADPH/cyt P-450 reductase, were identified by using electron spin
      resonance spin trapping with 5,5-dimethyl-1-pyrroline N-oxide (DMPO). The spin
      adducts of superoxide and hydroxyl radical (DMPO-OOH and DMPO-OH, respectively)
      were generated in the reaction of NCS with the NADPH/cyt P-450 reductase system.
      From kinetic analyses of DMPO-OOH generation as a function of the concentration
      of NCS, the Vmax/Km value of the reaction was 0.4 x 10(6) M-1min-1. In addition,
      we identified thiyl radical generation in this system in the presence of
      glutathione. These results indicate that NCS is a potent generator of free
      radicals in cells where cyt P-450 reductase is available. Moreover, it seems that
      free radicals, generated by enzymatic activation of NCS, are involved in
      cytotoxicity of NCS as well as in DNA damage.

PMID- 7811257
TI  - Kinetics of conformation change in cyanometmyoglobin following electron transfer
      monitored by magnetically induced circular dichroism spectrometry.
AB  - The characterization of the dynamics of conformational changes that accompany the
      ligand binding and dissociation reactions of myoglobin may provide insights into
      the events that control the physiological function of this oxygen storage
      protein. The cyanometmyoglobin system was chosen for this study because cyanide
      binds to the metmyoglobin state and dissociates upon reduction. The potential
      step spectroelectrochemical method was used here because the rate of
      cyanometmyoglobin reduction at an electrode can be controlled so that the rate of
      dissociation of the reduced cyanomyoglobin can then be followed.

PMID- 7811255
TI  - Characterization of one novel venom protease with beta-fibrinogenase activity
      from the Taiwan habu (Trimeresurus mucrosquamatus): purification and cDNA
      sequence analysis.
AB  - Several fibrinogenolytic proteases were isolated from the venom of Taiwan habu,
      Trimeresurus mucrosquamatus, a snake species belonging to the Crotalidae family.
      One protease with strong fibrinogenolytic activity was further purified to
      homogeneity through multiple-step chromatographies including ion-exchange
      chromatography, gel permeation and reversed-phase HPLC. In vitro, the purified
      enzyme cleaved beta-chain of fibrinogen molecules efficiently and showed
      relatively lower activity on alpha-chain, with almost no activity on gamma-chain
      even after a long period of incubation. Further characterization indicated that
      it is a single-chain polypeptide with molecular weight of about 28,000. Its
      stability at high temperatures (> 90 degrees C) distinguished it from the
      previously reported venom fibrinogenases. N-Terminal sequence analysis revealed
      that it is similar to batroxobin and ancrod, which were shown to possess either
      fibrinogen-clotting or antithrombotic effect. Polymerase chain reaction (PCR) was
      employed to amplify cDNAs constructed from the poly(A)+RNA of fresh venom glands
      of the same snake species to facilitate the cloning and sequencing of this
      important fibrinogenase. Sequencing several positive clones corresponding to the
      coding sequence of the enzyme revealed the existence of a family of novel
      thrombin-like fibrinogenases in the Taiwan habu, which are heat-stable and may be
      useful as strong antithrombotic agents.

PMID- 7811258
TI  - Structure-activity relationships of an anti-HIV peptide, T22.
AB  - T22 ([Tyr5,12,Lys7]-polyphemusin II) has been shown to have a strong anti-human
      immunodeficiency virus (HIV) activity comparable to that of 3'-azido-2',3'
      dideoxythymidine (AZT). We studied the structure-anti-HIV activity relationships
      of T22 and determined the following information. The number of Arg residues in
      the N-terminal and C-terminal regions of T22 is closely related with anti-HIV
      activity. Disulfide rings, especially the major disulfide ring, are indispensable
      for anti-HIV activity and maintenance of the secondary structure. Between two
      repeats of Tyr-Arg-Lys, which are a characteristic structure contained in T22,
      Tyr-Arg-Lys in the N-terminal portion is more closely related with anti-HIV
      activity. We found some compounds having a higher selectivity index (50%
      cytotoxic concentration/50% effective concentration) than that of T22.

PMID- 7811259
TI  - Enhanced superoxide production by membrane vesicles from Halobacterium halobium
      in a hyposaline environment.
AB  - Membrane vesicles were prepared from the halophilic archaebacterium,
      Halobacterium halobium, which was grown either in medium containing 4 M NaCl or
      in a relatively hyposaline medium containing 1.25 M NaCl. Membrane vesicles
      prepared from bacteria grown in the lower salt environment consumed more oxygen,
      oxidized more NADH and generated more superoxide than vesicles prepared from
      cells grown in the normal 4 M NaCl containing medium. The enhanced respiratory
      activity of the membrane fragments obtained from the halophile which was grown
      and assayed in a hyposaline environment, along with the concomitant increased
      flux in superoxide, demonstrate a relation between an environmental perturbation
      and an altered electron transport activity.

PMID- 7811260
TI  - Sequence of the 5'-flanking region of CYP3A5: comparative analysis with CYP3A4
      and CYP3A7.
AB  - Two genomic clones containing the 3'-end of CYP3A7, the whole 5'-flanking region
      plus the first exon of CYP3A5 were isolated from two different human genomic
      banks and sequenced. The 5'-flanking region of CYP3A5, from nucleotide -1 to 
      1434, was 60% and 59% similar with the corresponding regions of CYP3A4 and
      CYP3A7, respectively. However, the similarity increased to 74% when regions from
      nucleotide -1 to -700 were compared and dropped to less than 42% for regions
      upstream from -700. The CYP3A5 promoter contains a CATA box instead of the
      typical TATA box and a basic transcription element (BTE). Other consensus
      sequences previously found in CYP3A4 and CYP3A7 were also identified in the 5'
      flanking of CYP3A5 from -1 to -700. Both CYP3A5 and CYP3A7 genes appear to be
      tandemly associated and transcribed in the same direction on chromosome 7.

PMID- 7811261
TI  - A simple HPLC method for the determination of S-adenosylmethionine and S
      adenosylhomocysteine in rat tissues: the effect of vitamin B6 deficiency on these
      concentrations in rat liver.
AB  - A simple method using isocratic HPLC with ultraviolet detection was established
      for the simultaneous measurement of S-adenosylmethionine (SAM) and S
      adenosylhomocysteine (SAH) in rat tissues. The method provides rapid resolution
      of both compounds in a single run by direct injection of the perchloric acid
      extract of tissue, so that sampling procedures and analytical errors can be
      reduced in determining the SAM/SAH ratio, a measure of transmethylation
      reactions. The assay has a detection limit of 25 pmol and is linear in the range
      50-200 pmol. This procedure was applied to determine the change of SAM/SAH ratio
      in liver caused by vitamin B6 deficiency. The marked reduction of the SAM/SAH
      ratios in vitamin B6-deficient rats were due to a drastic rise in SAH
      concentration with a concurrent striking decrease in SAM concentration.

PMID- 7811262
TI  - Proteolysis of A beta peptide from Alzheimer disease brain by gelatinase A.
AB  - It has been recently reported that the 72 kDa proteolytic enzyme gelatinase
      A/type IV collagenase/matrix metalloproteinase 2 (MMP2) hydrolyzed the Lys 16-Leu
      17 peptide bond of a synthetic decapeptide (YEVHHQKLVFF) representing the soluble
      A beta sequence of amino acid residues 10-20. Our aim was to test if this enzyme
      could also degrade the insoluble 40-42 residues long A beta peptides purified
      from Alzheimer Disease brain. Our results indicate that MMP2 hydrolyzes A beta 1
      40 and A beta 1-42 peptides at Lys 16-Leu 17, at Leu 34-Met 35, and Met 35-Val 36
      peptide bonds. These results suggest that MMP2 has the ability of degrading A
      beta of AD in vitro. If this hydrolysis also occurs in the brain's extracellular
      matrix, the enzymatic action of gelatinase a could prevent the generation of
      amyloidogenic A beta 1-40(42).

PMID- 7811263
TI  - The pleckstrin homology domain of RAC protein kinase associates with the
      regulatory domain of protein kinase C zeta.
AB  - Binding proteins to the pleckstrin homology domain of RAC protein kinase were
      screened by using glutathione S-transferase fusion protein system. Proteins in
      CHO cell extract of approximate molecular mass of 76 kD and 200 kD bound
      specifically to the pleckstrin homology domain of RAC protein kinase in vitro.
      The 76 kD protein was identified as protein kinase C zeta by immunoblot analysis.
      Studies of the association between the pleckstrin homology domain-truncated
      mutants and protein kinase C zeta indicated that the amino-terminal portion of
      the pleckstrin homology domain is essential for the binding and the whole
      structure of the domain is important for the efficient binding to protein kinase
      C zeta. The pleckstrin homology domain of RAC protein kinase was shown to
      recognize the regulatory domain of protein kinase C zeta. The protein-protein
      interaction between RAC protein kinase and protein kinase C through the
      pleckstrin homology domain might be important for the regulation of these protein
      kinases.

PMID- 7811264
TI  - Phosphorylation of Rabphilin-3A by calmodulin-dependent protein kinase II.
AB  - Rabphilin-3A is a putative target protein for Rab3A small GTP-binding protein
      which is implicated in neurotransmitter release. We have examined here whether
      Rabphilin-3A is phosphorylated by calmodulin-dependent protein kinase II
      (CaMKII). Recombinant Rabphilin-3A was phosphorylated by CaMKII purified from rat
      brain. Two moles of phosphate were maximally incorporated into one mole of
      Rabphilin-3A. The phosphorylation sites were Ser34, Thr205, Thr209, and Thr537.
      These results suggest that the CaMKII-catalyzed phosphorylation of Rabphilin-3A
      may modulate neurotransmitter release.

PMID- 7811265
TI  - Human proteasome subunits from 2-dimensional gels identified by partial
      sequencing.
AB  - Human proteasomes consist of 14 major subunits which can be resolved by two
      dimensional polyacrylamide gel electrophoresis. Tryptic peptides from the
      subunits were sequenced. This allowed identification of all proteins in two
      dimensional electrophoresis gels with proteasome subunits whose sequences are
      known from cDNA. The results also precisely define the specificity of a panel of
      subunit-specific monoclonal antibodies. A new proteasome subunit (Z) was
      discovered. In contrast, the putative subunit MECL-1 could not be detected in
      human placenta proteasomes.

PMID- 7811266
TI  - Guinea pig membrane-bound aminopeptidase P is a member of the proline peptidase
      family.
AB  - Members of the newly recognized proline peptidase family share the ability to
      hydrolyze imide bonds and share six blocks of highly homologous amino acid
      sequences. We have found that guinea pig lung and kidney forms of aminopeptidase
      P, both forms bound to membranes via glycosyl phosphatidylinositol lipid anchors,
      share at least three of the six conserved blocks of amino acid sequences. In
      addition, aminopeptidase P acts as an aminoacylproline hydrolase and thus appears
      to be a member of the proline peptidase family.

PMID- 7811267
TI  - Immunoaffinity purifications of aminopeptidase P from guinea pig lungs, kidney
      and serum.
AB  - Previously, aminopeptidase P (AmP) has been purified from mammalian tissues by
      highly laborious multistep chromatography procedures. To simplify purifications,
      we raised a monoclonal antibody to guinea pig serum AmP and used the antibody to
      prepare an immunoaffinity matrix. The immunoaffinity matrix was used to obtain
      highly purified forms of AmP from guinea pig lungs, kidney and serum. The
      antibody is reactive with rat and human forms of AmP and may simplify procedures
      needed for their purifications.

PMID- 7811268
TI  - Calyculin A, a non-phorbol ester type tumor promotor, induced oxidative DNA
      damage in stimulated human neutrophil-like cells.
AB  - Calyculin A(CA) induced 8-hydroxydeoxyguanosine (8OHdG), typical of mutagenic
      oxidative DNA damage, in N-Formyl-Methionyl-Leucyl-Phenylalanine (FMLP)
      stimulated dimethyl sulfoxide(DMSO)-differentiated HL60(DMSO-HL60), which has
      characteristics similar to those of human neutrophils. CA enhanced O2-generation
      in FMLP-stimulated DMSO-HL60. CA by itself neither induced 8OHdG nor O2
      generation. FMLP by itself induced O2-generation, however, it did not induce
      8OHdG. These findings suggest that CA exerts its tumor promotion activity through
      modulating O2-generation and through inducing oxidative DNA damage and that a
      common bioactive peptide induces oxidative DNA damage under a certain condition.

PMID- 7811269
TI  - Isolation of Dictyostelium discoideum cytokinesis mutants by restriction enzyme
      mediated integration of the blasticidin S resistance marker.
AB  - We have developed an improved REMI (restriction enzyme-mediated integration)
      system for generating mutant Dictyostelium cells quickly and efficiently for
      systematic screening of cytokinesis mutants. By means of this system, three
      cytokinesis mutants that grow as giant and multinucleate cells were isolated from
      2,000 Dictyostelium transformants. Southern blot analysis of these mutants
      revealed that a single copy of the tag DNA was integrated into each genome. The
      tag with flanking genomic DNA at both ends was rescued from one of the mutants
      and reintroduced into the parental Ax2 strain. Homologous recombination of the
      rescued gene and the Dictyostelium genome led to the phenotypical changes
      expected for cytokinesis mutants.

PMID- 7811270
TI  - Heart fatty acid binding protein is a novel regulator of cardiac myocyte
      hypertrophy.
AB  - Heart fatty acid binding protein (H-FABP) is a 15kDa protein that mediates the
      passage of fatty acids from the plasma membrane to sites of lipid synthesis. We
      report here, for the first time, that H-FABP is a potent inducer of cardiac
      myocyte hypertrophy, stimulating an increase in cell surface area, protein
      synthesis and c-jun expression. A high affinity receptor for H-FABP has also been
      identified. Taken together, these data suggest that H-FABP may participate in the
      regulation of cardiac myocyte growth and differentiation.

PMID- 7811271
TI  - beta-Amyloid protein induces platelet aggregation and supports platelet adhesion.
AB  - The amyloid precursor protein (APP) is found in many cells including neurons,
      endothelial cells and blood platelets. Beta-amyloid protein (beta AP) is derived
      from APP and is deposited in brain and in cerebral microvasculature of
      individuals with Alzheimer's disease. In this study we demonstrate that beta AP
      interacts with human blood platelets. We found that human beta AP peptide (1-40)
      fibrils aggregate platelets and support their adhesion, and these interactions
      are mediated through platelet membrane integrin receptors.

PMID- 7811272
TI  - A variant of the human corticotropin-releasing factor (CRF) receptor: cloning,
      expression and pharmacology.
AB  - A variant of the human corticotropin-releasing factor receptor has been
      characterized. The variant has a 40-amino-acid deletion in the amino-terminal
      domain of the receptor and is the only form of this receptor detectable in the
      individual from which it was isolated. In contrast to the high affinity expressed
      by the normal human CRF receptor, the receptor variant fails to bind [125I]oCRF
      with high affinity in transfected COS-1 cells. High concentrations of human CRF
      are required to elevate intracellular cAMP levels in the cells transfected with
      the variant receptor; EC50 values of 301 and 0.55 nM were obtained in cell
      expressing the receptor variant and normal CRF receptors, respectively.

PMID- 7811273
TI  - Temperature-dependent Ca2+ mobilization induced by hypoxia-hypoglycemia in the
      monkey hippocampal slices.
AB  - Mobilization of [Ca2+]i in the monkey hippocampal slices during transient hypoxia
      hypoglycemia and KCl-induced depolarization was analyzed by microfluorometric
      imaging and anti-PIP2 immunohistochemistry. Hypoxia-hypoglycemia provoked the
      largest [Ca2+]i mobilization of CA-1 temperature-dependently whereas [Ca2+]i
      mobilization by KCl-induced depolarization occurred independent of the
      temperature in CA-2. Immunohistochemical analysis of the hippocampus after
      hypoxia-hypoglycemia showed an increased PIP2 staining preferentially in the
      perikarya of CA-1 neurons. These data suggest that release of Ca2+ from
      intracellular stores caused by PIP2 breakdown may induce elevated [Ca2+]i.

PMID- 7811274
TI  - A novel cyclic GMP stimulated phosphodiesterase from rat brain.
AB  - A cDNA clone for cyclic GMP Stimulated Phosphodiesterase (cGSPDE; PDE2) was
      isolated from a rat brain cDNA library. The cDNA has an open reading frame which
      encodes a protein of 928 amino acids of which 829 are identical with the reported
      bovine adrenal gland cGSPDE cDNA (Sonnenburg, W.K., Mullaney, P.J., and Beavo,
      J.A. (1991) J. Biol. Chem. 266, 17655-17661). Although the overall homology of
      these two cDNAs is high, they are distinctly different in their 5' ends, with the
      N-terminal 37 amino acids of the rat brain protein showing no homology with the N
      terminal end of the bovine adrenal protein. Hydrophilicity plots show that in
      contrast to the bovine adrenal cGSPDE, the N-terminal end of the rat brain cGSPDE
      is highly hydrophobic. Isolation and analysis of a genomic clone for cGSPDE from
      a rat genomic library shows the presence of an exon/intron junction at the Gln39
      codon. The cGSPDE cDNA we have isolated and that of Sonnenburg et al. represent
      alternatively spliced mRNA products from the same gene, with the brain isoform
      designed to be targeted to membranes.

PMID- 7811276
TI  - Does the eukaryotic large ribosomal subunit have a channel passing through it?
AB  - The large ribosomal subunit of the thermophilic fungus Thermomyces lanuginosus
      was treated with 2.96 M NH4Cl to remove specific complements of ribosomal
      proteins, and the core particles thereby derived were imaged by bright field
      transmission electron microscopy, and recurring views computed by single particle
      electron image analysis. A new characteristic projection was elucidated which
      showed a large depression or channel passing through the subunit. Such a channel
      has been perceived in the prokaryotic large ribosomal subunit under certain
      conditions and has been postulated to be the exit pathway for the nascent
      polypeptide chain, but its existence has not hitherto been demonstrated in
      eukaryotes.

PMID- 7811277
TI  - Molecular cloning of two small GTP-binding proteins from human skeletal muscle.
AB  - Two distinct cDNAs encoding small GTP-binding proteins were isolated from a human
      fetal skeletal muscle cDNA library. Nucleotide sequence analysis revealed that
      one clone encodes a protein of 218 amino acids, which shares highest amino acid
      identities (over 90%) with the members of YPT3 GTP-binding proteins subfamily and
      was termed H-YPT3; and the second clone encodes a protein of 201 amino acids,
      which exhibits strongest homology to rab1A, rab1B, and YPT1 at its N-terminus but
      diverges notably from these rab family members at the C-terminus. The second cDNA
      may represents a novel member of the small GTP-binding protein family and was
      designated H-ray. Northern blot analysis shows that both genes are ubiquitously
      expressed. Using a bacterial expression vector, each clone was overexpressed in
      Escherichia coli. The two bacterially produced proteins possess GTP-binding
      activity.

PMID- 7811275
TI  - Cyclin D1/cdk2 kinase is present in a G1 phase-specific protein complex Yi1 that
      binds to the mouse thymidine kinase gene promoter.
AB  - Our studies provide evidence for the presence of cyclin D1 in an early G1 cycle
      specific DNA binding complex Yi1. Previously we identified several complexes
      including Yi and E2F that at different times during G0 to S transition bind to
      three distinct DNA sequences (MT1, MT2, MT3) located in the mouse thymidine
      kinase upstream promoter. These various complexes contain DNA binding proteins
      (Sp1, E2F, p110, p60), cyclins A and E, cyclin-dependent kinase 2 (cdk2), and
      retinoblastoma-related proteins (pRB, p107). Here we report that Yi1 is different
      from the E2F complexes. Yi1 contains cyclin D1/cdk2 kinase as shown by using
      specific antibodies to cyclins, cdks and the Yi1 DNA-binding protein in gel
      retardation, western blotting, and immunoprecipitation assays. Yi1 binding is
      specific to a consensus sequence different from that of E2F.

PMID- 7811278
TI  - Sequence analysis of the 5'-flanking promoter region of the human somatostatin
      receptor 5.
AB  - We have determined the sequence of 2.2 kb of 5' flanking promoter region of the
      human somatostatin receptor 5 (hsstr5) gene. A number of widely distributed
      promoter elements were identified including AP1, AP2, AP3, E2A, GCF, and SP1
      consensus sequences. hsstr5/CAT gene fusions showed that the 0.9 kb of DNA
      immediately upstream of the ATG functions as a promoter in rat pituitary GH3 but
      not in CHO ovary cells. Insertion of this hsstr5 fragment in the anti-sense
      orientation led to a four fold reduction in CAT activity. Dibutyryl cAMP produced
      a three fold induction of CAT activity whereas estradiol and retinoic acid had no
      significant effect. These results indicate that we have identified a DNA fragment
      at the 5' end of the hsstr5 gene which contains both tissue-specific and
      regulated elements. The absence of CRE consensus sequence suggests that the cAMP
      effect is mediated by the multiple AP1 and AP2 sites.

PMID- 7811279
TI  - Unusual insulin binding to cells expressing an insulin receptor mutated at
      cysteine 524.
AB  - The involvement of cysteine 524 of the insulin receptor in an intermolecular
      (class I) disulfide bond between the two alpha-subunits was investigated using
      site-directed mutagenesis. The oligomeric structure of the mutated receptor was
      partially disrupted, although a significant portion of the receptor remained in
      its heterotetrameric form. Interestingly, the mutated insulin receptor
      heterotetramer was more susceptible than the wildtype receptor to reduction to
      heterodimers by low concentrations of dithiothreitol. Insulin binding to
      solubilized mutant receptors was normal and the mutant receptors had normal
      affinity for insulin, but insulin binding to cells expressing mutant insulin
      receptors displayed positive cooperativity. Cysteine 524 is most likely involved
      in a class I disulfide bond and receptors mutated at this site displayed unusual
      insulin binding properties only in the cellular environment.

PMID- 7811280
TI  - Cardiac myocyte differentiation induced by 3,5,3'-triiodo-L-thyronine (T3) in P19
      teratocarcinoma cells is accompanied by preferential binding of RGG(T/A)CA direct
      repeats spaced by 4 base pairs in the DNA.
AB  - When treated with T3, P19 cells differentiate into ultrastructurally proven
      cardiac myocytes and express the cardiac ventricular specific marker ventricular
      myosin light chain 2V. This differentiation is irreversibly induced in culture
      during the first 48 hrs of exposure to T3. We studied the binding of P19
      indigenous transcription factors of the Steroid-Thyroid-Retinoic superfamily of
      nuclear receptors to oligonucleotide response elements bearing direct, inverted
      and palindromic repeats of the consensus sequence RGG(T/A)CA. Electrophoretic
      mobility shift assays showed a preference in T3-treated P19 cells for binding
      RGG(T/A)CA "half sites" in direct repeat orientation separated by 4 base pairs.
      The specificity of binding was confirmed in competition experiments. This finding
      suggests that target genes bearing thyroid response elements spaced by 4 base
      pairs in their promoter regions play an important role in the cardiac
      differentiation induced by T3 in P19 teratocarcinoma cells.

PMID- 7811281
TI  - Production of interleukin-10 by mouse glial cells in culture.
AB  - In this study, we examined the production of IL-10 by glial cells in vitro. IL-10
      was detected in the culture supernatants of microglia and in the cell lysate of
      astrocytes by enzyme-linked immunosorbent assay. We also detected IL-10 mRNA and
      IL-10 receptor mRNA in both microglia and astrocytes. The expression of IL-10
      mRNA, as well as the production of IL-10 protein, was enhanced by the stimulation
      of these cells with lipopolysaccharide(LPS). Recombinant IL-10 effectively
      suppressed both LPS-induced cytokine production and IFN-gamma-induced class II
      major histocompatibility complex antigen expression by microglia. These results
      suggest that IL-10 is produced in the CNS and plays a role as an inhibitory
      regulator in the CNS cytokine network.

PMID- 7811282
TI  - Chicken lacks the testis specific isozyme of angiotensin converting enzyme found
      in mammals.
AB  - Chicken angiotensin converting enzyme (ACE) cDNA was cloned based on homology to
      the mouse ACE sequence. The chicken ACE protein is highly homologous to the
      somatic isozyme of ACE found in human, mouse, bovine, and rabbit. Like the
      mammalian somatic forms, the chicken enzyme consists of two putative zinc binding
      sites at the center of two homologous domains. All known functional residues are
      absolutely conserved. Unlike the mammals, no evidence for a single domain, testis
      specific form of ACE was found in the chicken testis by either Northern blot or
      enzyme assay. This result is unexpected since the adult mammalian testis
      expresses one of the highest tissue levels of ACE.

PMID- 7811283
TI  - A genetic linkage map of the mouse using an expanded production system of
      restriction landmark genomic scanning (RLGS Ver.1.8).
AB  - We have developed an expanded system (RLGS Ver.1.8) for producing RLGS patterns
      that result in a 16-fold increase in the number of gels produced and a 10-fold
      reduction in the total cost per gel. The major modifications include: 1)
      performing the blocking and labeling step without phenol extraction or ethanol
      precipitation; 2) minimizing the reaction volume and the enzyme units in each
      step; 3) developing a long vertical agarose disc gel electrophoresis for the 1st
      dimension; and 4) developing a new apparatus for multiplex vertical 2nd
      dimensional electrophoresis. RLGS Ver.1.8 was used with a new combination of
      restriction enzymes to identify variation for 209 loci between C57BL/6J and
      DBA/2J. Twenty-six BXD RI strains were analyzed and 195/209 loci were genetically
      mapped. These loci were mapped in one week of laboratory work by two people. This
      system provides an important tool for the genetic analysis of new loci in similar
      genetic resources.

PMID- 7811284
TI  - Involvement of the estrogen receptor in the growth response of pituitary tumor
      cells to interleukin-2.
AB  - Having recently demonstrated in separate studies that the T-cell cytokine,
      interleukin-2, induces the growth of the pituitary tumor cell line GH3 and that
      in the same cells, the estrogen receptor mediates the mitogenic effect of growth
      factors, we sought here to determine whether the estrogen receptor was involved
      in the response to interleukin-2. We demonstrate that under steroid and serum
      free growth conditions, the pure antiestrogen, ZM 182780, blocks the mitogenic
      response of GH3 cells to interleukin-2. Transfection studies with a reporter
      plasmid responsive to the transcriptionally active estrogen receptor show that
      even in the absence of ligand, the estrogen receptor in these cells is
      transcriptionally active and this can be increased by interleukin-2. Further
      studies on the two estrogen receptor regulated proteins, the progesterone
      receptor and prolactin, showing that the levels of these proteins were increased
      by exposure of cells to interleukin-2, support the idea of a cross-talk between
      the estrogen receptor and interleukin-2 signal transduction.

PMID- 7811287
TI  - Mapping studies of two G protein-coupled receptor genes: an amino acid difference
      may confer a functional variation between a human and rodent receptor.
AB  - We recently isolated two orphan human G protein-coupled receptor genes designated
      GPR1 and GPR6. The gene GPR1 was shown to be transcribed abundantly but only in
      the hippocampus. Here we report the cloning of the rat GPR1 gene and report the
      absence of expression in hippocampus, demonstrating a functional variation for
      this receptor in these two species. The evolutionary history of an important
      sequence difference in the gene GPR1 in primate and rodent species has been
      examined. In contrast extensive mapping of gene GPR6 mRNA in rat brain was in
      keeping with the described distribution in human brain.

PMID- 7811286
TI  - A mammalian serine/threonine kinase receptor specifically binds BMP-2 and BMP-4.
AB  - Bone morphogenetic proteins (BMPs) are a class of related growth and
      differentiation factors within the TGF-beta superfamily of proteins which are
      known to induce cartilage and bone formation in adult animals and to be involved
      in many inductive events throughout embryonic development. Here we describe the
      molecular cloning and characterization of a mammalian receptor, CFK-43a, which
      specifically binds BMP-2 and BMP-4. This molecule is a member of the
      serine/threonine kinase receptor family which includes receptors for other TGF
      beta superfamily members. CFK-43a binds other BMP family members with lower
      affinity, but does not bind TGF-beta. During embryogenesis, in situ hybridization
      analysis indicates that CFK-43a mRNA is localized in developing skeletal tissues
      in a complementary fashion to the transcripts for its ligands.

PMID- 7811285
TI  - Membrane orientation of the SIV fusion peptide determines its effect on bilayer
      stability and ability to promote membrane fusion.
AB  - The amino terminal segment of the gp32 glycoprotein of SIV has been identified as
      an important region for membrane fusion. A synthetic dodecapeptide corresponding
      to this amino terminal segment, SIVwt, can promote the fusion of liposomes. This
      peptide inserts at an oblique angle into the membrane. If the amino acid sequence
      of this peptide is changed, while maintaining the same amino acid composition,
      the resulting peptide, SIVmutV, no longer promotes fusion and it is oriented
      perpendicular to the plane of the bilayer. In the present work we demonstrate
      that SIVwt, but not SIVmutV, can lower the bilayer to hexagonal phase transition
      temperature of model membranes composed of dipalmitoleoyl
      phosphatidylethanolamine. In addition the SIVwt promotes the formation of
      structures which give rise to isotropic 31P NMR signals in mixtures with
      monomethyldioleoyl phosphatidylethanolamine. These structures are not formed with
      SIVmutV and their formation with SIVwt is suppressed with
      lysophosphatidylcholine. Taken together these results suggest that the observed
      correlation between oblique insertion of viral fusion peptides into membranes and
      their fusogenicity may be a consequence on these peptides increasing negative
      monolayer curvature.

PMID- 7811288
TI  - Molecular cloning of a novel thyroid/steroid receptor superfamily gene from
      cultured rat neuronal cells.
AB  - Brain neuronal cells in primary culture provide one system for the analysis of
      neuronal development, including apoptosis. By PCR amplification, with primers
      designed from conserved sequences among nuclear receptors, a novel member of the
      thyroid/steroid receptor superfamily was identified from forebrain neuronal cells
      undergoing apoptosis and designated as NOR-1 (neuron derived orphan receptor). A
      cDNA clone of NOR-1 encodes a 68kDa, 628 amino acid residue-containing protein,
      with an amino acid sequence highly homologous to the Nur77 family in its DNA
      binding domain and moderately so in its putative ligand-binding domain. Using
      mobility shift assay, we showed that the NOR-1 protein binds to the B1a response
      element which has been identified as the target sequence of the Nur77 family,
      suggesting that three members of the Nur77 family may transactivate common target
      gene(s) at different situations.

PMID- 7811289
TI  - Identification of 10-kDa proguanylin as a major guanylin molecule in human
      intestine and plasma and its increase in renal insufficiency.
AB  - Guanylin is a 15-amino acid peptide that acts on intestinal guanylate cyclase,
      thereby regulating intestinal fluid and electrolyte transport through the second
      messenger, cyclic GMP. Using synthetic rat guanylin, we prepared an antiserum
      that recognizes human and rat guanylin equally on a molar basis and developed a
      sensitive radioimmunoassay (RIA). The major endogenous guanylin molecule in human
      intestine and plasma is 10-kDa proguanylin, 15-amino acid guanylin being a minor
      component. Human guanylin is distributed widely from the duodenum to colon, the
      highest contents being in the ileum and proximal colon. The plasma concentration
      of immunoreactive guanylin in the normal individuals tested was 31.2 +/- 3.0
      fmol/ml (mean +/- SE) and that in patients with chronic renal failure who were
      undergoing hemodialysis 7,924 +/- 2,140 fmol/ml. The RIA we established is a
      promising tool for clarifying the physiological functions and pathophysiological
      significance of guanylin in water and electrolyte homeostasis.

PMID- 7811290
TI  - ROR gamma: the third member of ROR/RZR orphan receptor subfamily that is highly
      expressed in skeletal muscle.
AB  - In this study, we describe the identification and cloning of a novel member of
      the nuclear receptor superfamily. This orphan receptor, referred to as ROR gamma,
      belongs to the ROR/RZR subfamily. The open reading frame of ROR gamma encodes a
      protein of 560 amino acid residues with a predicted molecular mass of 63 kD. The
      amino acid sequence of ROR gamma exhibits a 50 and 51% identity with those of ROR
      alpha/RZR alpha and RZR beta, respectively, whereas the DNA-binding domains were
      89% identical. ROR gamma was localized on human chromosome 1. Northern blot
      analysis using RNA from multiple tissues indicated that ROR gamma is expressed in
      several tissues but is most highly expressed in skeletal muscle.

PMID- 7811291
TI  - Activation of the tyrosinase gene promoter by neurofibromin.
AB  - Neurofibromatosis type 1 (NF1) is a hereditary cancer syndrome, characterized by
      cafe-au-lait skin spots and multiple neurofibromas. A gene linked to NF1 encodes
      neurofibromin, an established function of which is to stimulate intrinsic GTPase
      activity of ras protein. By transiently coexpressing a neurofibromin cDNA in a
      melanoma cell line, we show that neurofibromin increases the expression of a
      reporter gene under the control of the tyrosinase gene promoter. Tyrosinase is a
      rate-limiting enzyme in melanin biosynthesis and is expressed only in melanin
      producing cells. Functional analysis of neurofibromin cDNAs suggests that the
      domain related to a GTPase-activating protein is mainly responsible for this
      induction. These results suggest that neurofibromin functions as a regulator of
      melanogenesis, a process specific to the melanocytes derived from the neural
      crest.

PMID- 7811292
TI  - Tumor necrosis factor alpha production enhancers with a phenylphthalimide
      skeleton.
AB  - N-2,6-Dialkylphenylphthalimides were found to be strong enhancers of 12-O
      tetradecanoylphorbol-13-acetate (TPA)-induced tumor necrosis factor (TNF)-alpha
      production by human leukemia cell line HL-60. Among these compounds, 2-(2,6
      diisopropylphenyl)-1H-isoindole-1,3-dione (PP-33) showed the most potent activity
      (optimum concentration of 10 microM), indicating that the bulkiness of the alkyl
      groups at the 2 and 6-positions of the phenyl ring moiety is crucial for the
      activity. Its fluorinated derivative, 2-(2,6-diisopropylphenyl)-4,5,6,7
      tetrafluoro-1H-isoindole-1,3-dio ne (FPP-33) showed the activity at very low
      concentrations (optimum concentration of 0.1 microM).

PMID- 7811293
TI  - The C-terminus of the B cell activator Oct-2 functions as an activation domain in
      yeast.
AB  - Oct-1 and Oct-2 are human transcriptional activators that bind to the same DNA
      element but activate distinct sets of genes. We expressed these factors in S.
      cerevisiae and observed greater than 5-fold stimulation of a lacZ reporter gene
      only with Oct-2. Transfer of the Oct-2 C-terminal domain onto either Oct-1
      (Oct1.2) or a nonactivating DNA-binding domain from GAL4 created activators
      capable of greater than 15 and 10-fold stimulation of activity, respectively.
      Thus, the C-terminus of Oct-2 is sufficient to confer activation potential to
      nonactive DNA-binding fragments in yeast.

PMID- 7811294
TI  - Activation of human T helper 1 and DNAase expression in CD4+ T cells induced by
      short immunomodulating peptides.
AB  - Activation of human T helper 1 cells took place when lymphomononuclear cells from
      healthy donors were incubated in the presence of short synthetic peptides
      encompassing sequences present in extracellular matrix proteins. Active peptides
      conformed to a common structural pattern ("2-6-11 motif") [N.Lopez-Moratalla et
      al., Biochem. Biophys. Acta (1994) 1221, 153-158] conferring immunomodulating
      properties. The release of IL-2 and IFN gamma, as well as LAK and NK-dependent
      cytotoxicity induced by these peptides, could be blocked by anti-HLA-DR antibody.
      Activated CD4+ cells isolated from the mixed incubated population contained
      secretion granules with DNAase activity. These results suggest that these
      immunomodulating peptides presented by HLA-II play a key role in the
      differentiation of CD4+ T cells towards a Th1 functional phenotype.

PMID- 7811295
TI  - Sequence analysis of the third dnaK homolog gene in Synechococcus sp. PCC7942.

PMID- 7811296
TI  - Use of in vitro human metabolism studies in drug development. An industrial
      perspective.

PMID- 7811297
TI  - The relative hypolipidaemic activity and hepatic effects of ciprofibrate
      enantiomers in the rat.
AB  - The aim of this study was to establish whether the individual enantiomers of
      racemic ciprofibrate, a potent hypolipidaemic agent and peroxisome proliferator,
      differ significantly in either pharmacological potency or toxic potential. After
      a single oral dose to male Fischer F344 rats at dosages below 10 mg/kg, S(-)
      ciprofibrate produced slightly, but statistically significantly, greater
      reductions in plasma concentrations of cholesterol than R(+) ciprofibrate.
      Similarly, at low concentrations in F344 rat hepatocyte cultures, S(-)
      ciprofibrate produced slightly, but statistically significantly, greater
      inductions of peroxisomal beta-oxidation activity than R(+) ciprofibrate.
      However, after seven daily doses, the differences in pharmacological effects of
      the two enantiomers were no longer apparent. Furthermore, in contrast to its
      effects in vitro, R(+) ciprofibrate produced slightly, but statistically
      significantly, greater inductions of peroxisomal beta-oxidation activity in vivo
      than S(-) ciprofibrate. These observations may be possibly explained on the basis
      that following multiple dosing, plasma concentrations of R(+) ciprofibrate 24 hr
      post-dose were greater than those of its optical antipode. Thus the slightly
      greater potency of the S(-) enantiomer after a single dose may have been overcome
      by the greater plasma concentrations of the less potent enantiomer. Both
      enantiomers produced similar reductions in plasma concentrations of thyroxine.
      The data indicate that at low dosages S(-) ciprofibrate is a slightly more potent
      hypolipidaemic agent after a single dose in rats and a slightly more potent
      peroxisome proliferator at low concentrations in vitro. However, following
      multiple dosing, both enantiomers produced changes in plasma concentrations of
      lipids, hepatic enzyme activities and plasma concentrations of thyroxine which
      were of comparable magnitude to those produced by the racemate. Since these early
      changes have been linked mechanistically to the chronic toxicity of the racemate
      in the rat, it could be predicted that the individual enantiomers of ciprofibrate
      under conditions employed in chronic safety studies, would produce the same
      spectrum of rodent toxicity as the racemate.

PMID- 7811298
TI  - Promotion of oxidative damage to arachidonic acid and alpha 1-antiproteinase by
      anti-inflammatory drugs in the presence of the haem proteins myoglobin and
      cytochrome C.
AB  - A mixture of myoglobin and hydrogen peroxide (H2O2) causes peroxidation of
      arachidonic acid. This peroxidation is greatly accelerated by adding
      phenylbutazone, which is effective even in the absence of H2O2. A wide range of
      other drugs was examined for their ability to exert similar pro-oxidant effects.
      We found that meclofenamic acid and flufenamic acid stimulated myoglobin
      dependent lipid peroxidation, but only in the presence of H2O2. Ascorbic acid
      inhibited peroxidation both in the presence and in the absence of these drugs.
      Phenylbutazone, meclofenamic acid and flufenamic acid could also cause damage to
      proteins (as measured by inactivation of alpha 1-antiproteinase) in the presence
      of myoglobin and H2O2. The mitochondrial protein cytochrome c can also stimulate
      lipid peroxidation in the presence of H2O2. Phenylbutazone and meclofenamic acid,
      but not flufenamic acid, enhanced the peroxidation, which was again inhibited by
      ascorbic acid. However, only phenylbutazone caused inactivation of alpha 1
      antiproteinase in the presence of cytochrome c and H2O2. Since respiring
      mitochondria generate superoxide radicals and H2O2, catalysis of lipid
      peroxidation and of the formation of drug-derived radicals by cytochrome c could
      be a mechanism contributing to mitochondrial damage by drugs.

PMID- 7811299
TI  - Disruption of canalicular function in isolated rat hepatocyte couplets caused by
      cyclosporin A.
AB  - Isolated rat hepatocyte couplets were used to study the effects of different
      concentrations of cyclosporin A in relation to canalicular function. Canalicular
      function was assessed by counting the percentage of couplets which were able to
      accumulate the fluorescent cholephile cholyl lysyl fluorescein (CLF) into the
      canalicular vacuole between the two cells, i.e. canalicular vacuole accumulation
      (CVA). At lower doses, the immunosuppressor increased the CVA, reaching 121 +/-
      3.86% of control at 25 nM cyclosporin A. However, higher doses of cyclosporin A
      induced a concentration-dependent inhibition of CVA to 64.0 +/- 3.51% of control
      at 100 nM. Modifications in canalicular area (as % couplet area) were also
      observed. Image analysis of the fluorescent image showed that cyclosporin A (25
      nM) increased canalicular area by 25% (of control); however, this parameter
      decreased to 36% of control at 100 nM cyclosporin A. In addition, at 100 nM,
      cyclosporin A reduced the proportion of couplets retaining CLF within the
      canaliculus to 75.0 +/- 6.59% of control. Treatment of couplets with cyclosporin
      A (0-2 microM) for 15 min revealed that reduced glutathione (GSH) intracellular
      content does not change significantly at these doses. However, alteration in
      pericanalicular F-actin at 100 nM cyclosporin A may be an important factor in the
      disruption of the canalicular function induced by higher doses of the
      immunosuppressor.

PMID- 7811300
TI  - Pretranslational induction of cytochrome P4501A enzymes by beta-naphthoflavone
      and 3-methylcholanthrene occurs in different liver zones.
AB  - Most of the cytochrome P450 (CYP) genes are expressed in an uneven, zonated
      pattern in the liver. Factors regulating this regionally restricted expression
      are not well known. In this study we have analysed cell lysates obtained from
      opposite zones of rat liver by infusing digitonin to the perfused liver to study
      the zonation of CYP1A1 and CYP1A2 induction. 3-Methylcholanthrene induced CYP1A1
      protein in perivenous cells, while a low dose of beta-naphthoflavone caused
      periportal induction. Analysis of CYP1A1 mRNA from cell lysates by reverse
      transcriptase-coupled polymerase chain reaction (RT-PCR) and in situ
      hybridization experiments both demonstrated that this inducer-specific
      differently localized effect occurred at the pretranslational level. A
      corresponding difference in the regional pattern of CYP1A2 induction was seen:
      induction by beta-naphthoflavone reversed the constitutive perivenous pattern
      into a periportal CYP1A2 mRNA pattern while induction after 3-methylcholanthrene
      treatment was more panacinar. Attempts to identify the regiospecific factors
      involved were made by comparing the in vitro induction of CYP1A1 by beta
      naphthoflavone and 3-methylcholanthrene in hepatocytes isolated from the
      periportal and perivenous region. However, after isolation, induction seemed to
      be independent of the source of the cells. Our results demonstrate the existence
      in the liver of regionally acting factors that mediate the induction of CYP1A1
      and 1A2 in a local and inducer-specific fashion. These factors could be Ah
      receptor associated binding proteins operating in vivo, but no longer in isolated
      cells.

PMID- 7811301
TI  - Relationship between cytochrome P450 2E1 and acetone catabolism in rats as
      studied with diallyl sulfide as an inhibitor.
AB  - Previous studies have demonstrated that cytochrome P450 2E1 (P450 2E1) catalyzes
      the oxidation of acetone in vitro. The present study was designed to determine
      the importance of P450 2E1 in the catabolism of acetone in rats using diallyl
      sulfide (DAS) as an inhibitor of this enzyme. After a single intragastric dose of
      DAS, blood samples were collected from rats at different time points, and blood
      acetone concentrations were measured by gas chromatography. In a low DAS dose (50
      mg/kg body weight) group, the maximum acetone level of 6-fold higher than the
      normal level was reached at 6 hr; the acetone level returned to normal at 48 hr.
      In a high dose (200 mg/kg) group, the maximum acetone level of 9-fold higher than
      the normal level was reached at 12 hr; the acetone level returned to normal at 60
      hr. The turnover time and fractional turnover rate of elevated acetone were 15.8
      +/- 0.5 hr and 0.054 +/- 0.001 hr-1, respectively, for the low dose, and 19.2 +/-
      0.6 hr and 0.046 +/- 0.005 hr-1, respectively, for the high dose. In a chronic
      experiment, DAS (50 and 200 mg/kg, i.g.) was given to rats daily for 29 days, and
      elevated blood acetone levels were observed during the entire experimental
      period: 2.0 to 2.8 micrograms/mL for the low dose and 3.4 to 3.9 micrograms/mL
      for the high dose at 24 hr after the 1st, 7th, 14th and 28th doses versus 0.8 to
      0.9 micrograms/mL for the control. The increase of blood acetone level was
      closely related to the decreases of N-nitrosodimethylamine (NDMA) demethylase
      activity and P450 2E1 content in liver microsomes. Consistent with the lack of
      cumulative effect from the multiple doses of DAS on acetone level, rather stable
      levels of the DAS metabolites, diallyl sulfoxide (45.0 micrograms/mL, range: 33.8
      to 58.6 micrograms/mL) and diallyl sulfone (11.7 micrograms/mL, range: 6.9 to
      15.6 micrograms/mL), were observed at 24 hr after the 1st, 7th, 21st and 28th
      doses with DAS (200 mg/kg) in the chronic experiment. It is likely that the
      inactivation and inhibition of P450 2E1 by DAS and its metabolites block the
      oxidation of acetone and cause its elevation in blood. The results strongly
      suggest an important role of P450 2E1 in acetone catabolism under physiological
      conditions.

PMID- 7811302
TI  - Effects of a novel N-methyl-D-aspartate (NMDA) receptor antagonist, 3,3'-dimethyl
      3,4,3',4'-tetrahydro-6,8,6',8'-tetramethoxy-[10,10' -bi-2- oxanthracene]-4,9,9'
      (1H,1'H)-triol 4-acetate (ES-242-1), on NMDA-induced increases of intracellular
      Ca2+ concentration in cultured hippocampal neurons.
AB  - The effects of a novel N-methyl-D-aspartate (NMDA) receptor antagonist, ES-242-1
      (3,3'-dimethyl-3,4,3',4'-tetrahydro-6,8,6',8'-tetramethoxy-[10,10' - bi-2
      oxanthracene]-4,9,9'-(1H,1'H)-triol 4-acetate), on NMDA-induced increases of
      intracellular Ca2+ concentration in cultured hippocampal neurons were examined.
      ES-242-1 selectively blocked the NMDA-induced increase in intracellular free Ca2+
      concentration ([Ca2+]i), but not the [Ca2+]i increase stimulated by quisqualate
      or kainate. The effect of ES-242-1 appeared in the slow development of a blockade
      of [Ca2+]i (half blocking time: 90 sec) when 100 microM NMDA was applied with 10
      microM ES-242-1, whereas the initial [Ca2+]i rise was attenuated by 10 microM ES
      242-1 when the latter was applied with a lower concentration of NMDA (10 microM).
      This is consistent with a previous observation that ES-242-1 binds to both the
      transmitter recognition site and the channel domain. The blockade by ES-242-1 was
      reversed by washing. In contrast, the blockade by MK-801 was not relieved easily
      by washing. These results suggest that ES-242-1 blocks the NMDA-induced [Ca2+]i
      increase due to a combination of two well-recognized mechanisms, which are
      different from that of MK-801, at the NMDA receptor.

PMID- 7811303
TI  - Benzimidazoles, potent anti-mitotic drugs: substrates for the P-glycoprotein
      transporter in multidrug-resistant cells.
AB  - P-glycoprotein is though to mediate the energy-dependent efflux of many
      structurally and functionally unrelated lipophilic compounds. Presently, the
      molecular mechanism underlying the binding and efflux of drugs by P-glycoprotein
      is not well understood. However, it has been suggested that two planar benzene
      ring structures and a cationic charge are commonly found in many drugs that
      interact with P-glycoprotein. The benzimidazoles (BZs) are potent anti-tumour,
      anti-fungal and anti-parasitic agents, whose mode of action is thought to result
      from their inhibition of microtubule functions. Although other classes of
      microtubule inhibitors, such as colchicine and vinblastine, have been studied
      extensively with respect to their interaction and efflux by P-glycoprotein, the
      BZ group of drugs has not been characterized. In this study, we have
      characterized the interaction of BZ with multidrug-resistant cells and found that
      resistant cells accumulated substantially less BZ compared with drug-sensitive
      cells. Furthermore, BZ was more toxic to sensitive than to drug-resistant cells,
      suggesting that BZ is likely to be a substrate for the P-glycoprotein drug efflux
      pump. In addition, we used a photoactive analogue of BZ ([125I]ASA-BZ) to
      demonstrate a direct binding between BZ and P-glycoprotein. Results showing that
      a molar excess of vinblastine, unmodified BZ, verapamil and rhodamine 123, but
      not colchicine, inhibited the photoaffinity labelling of P-glycoprotein by
      [125I]ASA-BZ confirmed the binding specificity of BZ to P-glycoprotein. Protease
      digestion of [125I]ASA-BZ photoaffinity labelled P-glycoprotein yielded two
      peptides that were similar to those obtained with other P-glycoprotein-associated
      drugs, e.g. azidopine and iodoaryl azidoprazosin. Taken together, these results
      demonstrate a direct and specific interaction between P-glycoprotein and BZ in a
      manner that is probably similar to other previously characterized P-glycoprotein
      associated drugs.

PMID- 7811304
TI  - Oxidative metabolism of mitoxantrone by the human neutrophil enzyme
      myeloperoxidase.
AB  - The anti-cancer drug mitoxantrone is readily oxidized by the human heme enzyme
      myeloperoxidase (MPO) and H2O2. Direct oxidation yielded up to three products,
      which depended on the ratio of H2O2 to mitoxantrone. At an H2O2: mitoxantrone
      ratio of 1.0, one major product was obtained, with a spectrum and HPLC retention
      time identical to that resulting from oxidation by horseradish peroxidase. This
      metabolite is a substituted hexahydronaphtho[2,3-f]quinoxaline-7,12-dione and has
      been discovered in the urine of patients treated with mitoxantrone, hence
      implicating MPO in the in vivo metabolism of mitoxantrone. At higher
      concentrations of H2O2, the oxidation of mitoxantrone was more complex, with two
      further metabolites being identified. When mitoxantrone was incubated with
      neutrophils that had been stimulated with phorbol myristate acetate, it was
      oxidized by an MPO-dependent mechanism. Therefore, it appears that MPO may play a
      significant role in the clinical activity displayed by mitoxantrone against acute
      myelogenous leukemias, as neutrophils, monocytes and their bone marrow precursors
      contain high levels of the enzyme.

PMID- 7811305
TI  - Correlation of the response to nitroglycerin in rabbit aorta with the activity of
      the mu class glutathione S-transferase.
AB  - The relationship between the activity of glutathione S-transferases (GSTs),
      especially the mu isozyme, and the production of responses to nitroglycerin (GTN)
      was investigated in rabbit aorta. GST mu isozyme activity was measured using
      trans-stilbene oxide (TSO) as a substrate. Each aorta was divided into four
      parts, two of which were frozen for enzymatic analyses while the remaining two
      were used to measure the effects of GTN (0.5 microM), i.e. the increase in cGMP
      levels and the corresponding relaxation. Thus, all three measures were obtained
      in each individual rabbit aorta. Eight different rabbits were studied. An
      excellent correlation was obtained between the rise in cGMP and the mu isozyme
      activity (r2 = 0.948). A good correlation was also obtained between TSO activity
      and the relaxation response to GTN. Total GST activity did not correlate well
      with either cGMP increases or percent relaxation. These observations indicate
      that the activity of the mu isozyme measured using TSO and not the total GST
      correlates with the responses to GTN in the in vitro rabbit aorta model.

PMID- 7811306
TI  - Characterization of putrescine and cadaverine export in mammalian cells. A
      pharmacological approach.
AB  - We characterized the mechanism(s) involved in the efflux of putrescine/cadaverine
      from cultured mammalian cells using various pharmacological agents. Verapamil and
      quinine inhibited putrescine and cadaverine export in monocytic-leukemic RAW 264
      and H35 hepatoma cells in a concentration-dependent manner with an IC50 in the
      micromolar range. Verapamil, which inhibits L-type calcium channels, inhibited
      putrescine export, regardless of whether calcium was present in the extracellular
      medium or not. Furthermore, the export of putrescine in the absence of verapamil
      did not appear to depend upon extracellular calcium. Neither intracellular
      calcium, external sodium, changes in intracellular pH nor phosphorylation
      affected the levels of putrescine export independently from changes in
      intracellular putrescine levels. The data suggest that verapamil and quinine
      inhibit putrescine/cadaverine efflux from the cell by binding directly to an
      integral membrane protein.

PMID- 7811307
TI  - Expression of a human renal sodium nucleoside cotransporter in Xenopus laevis
      oocytes.
AB  - In this study, Xenopus laevis oocytes injected with poly(A)+ RNA (mRNA) isolated
      from human kidney were used to express a Na(+)-nucleoside cotransporter. Na(+)
      stimulated [3H]thymidine uptake was enhanced 2-3-fold in oocytes injected with 50
      ng poly(A)+ RNA and 4-5-fold in oocytes injected with 20 ng of a size
      fractionated human renal cortex mRNA fragment (2-3 kb) in comparison with water
      injected oocytes. Na(+)-dependent thymidine uptake in oocytes injected with the 2
      3 kb mRNA fragment was inhibited significantly by thymidine and guanosine but not
      by formycin B, consistent with the N4 Na(+)-nucleoside cotransporter. The Km (28
      microM) of Na(+)-dependent thymidine uptake in the oocytes injected with the 2-3
      kb mRNA fragment was similar to the Km (27 microM) of Na(+)-dependent thymidine
      uptake obtained in human renal brush border membrane vesicles. These data suggest
      for the first time that a Na(+)-nucleoside cotransporter from human kidney can be
      expressed in X. laevis oocytes.

PMID- 7811308
TI  - CGPCSD survey results. Council of Graduate Programs in Communication Sciences and
      Disorders.

PMID- 7811309
TI  - New temporal bone pathology registry enhances opportunities for hearing and
      balance research.

PMID- 7811310
TI  - Billboards alert parents.

PMID- 7811311
TI  - Destiny is in the data. A wake-up call for outcome measures.

PMID- 7811312
TI  - A few good men.

PMID- 7811313
TI  - Perspectives on the male speech-language pathologist.
AB  - Although many professions are reporting greater gender neutrality, the opposite
      appears to be the case in speech-language pathology and audiology. The number of
      men in speech-language pathology and audiology has always been small. In 1925,
      40% of the original members of the American Academy of Speech Correction were
      male (Bender, 1989). Each subsequent decade has seen the gender gap between male
      and female professionals widen (see chart illustrating the steady decline of male
      ASHA members between the years 1968 and 1992). When one considers only speech
      language pathology, the gap between numbers of males and of females is even
      greater. According to ASHA's membership database, in December 1993 only 6.0% of
      ASHA-certified speech-language pathologists were men (ASHA, 1993).

PMID- 7811314
TI  - Tender gender issues.
AB  - For 40 years, I have been a male on this planet. Nearly half of those years I
      have proudly worked as a speech-language pathologist. Some say that I don't seem
      like other men, whatever that means. I am told that I am sensitive, caring, even
      loving. Why do some believe that women corner those markets? Once I was invited
      to participate in a men's group, a collection of men from throughout the
      community who talk about issues that relate to men. What fun, I thought. It
      wasn't long before I realized that I did not belong in that group. Discussions
      turned to bashing--women, work, life. The other group members wanted me to
      continue to participate because they indicated that I represented another side--a
      happy side. You see, I love my wife. I love my kids, too. What's more, I enjoy my
      work and sincerely believe that it is important. I value the opportunity to work
      with student, faculty, and administrative colleagues I respect. I guess my views
      were not too popular with the men's group.

PMID- 7811315
TI  - Gender bias in language testing.
AB  - Although our profession is concerned with recruiting males, we must continue to
      be concerned about equality for females. The negative influence of gender bias on
      women and their roles has been addressed by the professions in terms of language
      use (Lynch, 1983) and discrimination in academic settings (Davis, 1994). But we
      have not considered standardized test bias related to women. Since language is
      generally recognized as a major conveyor of the societal bias against women, a
      reasonable question to ask is, Do language tests reflect a gender bias?

PMID- 7811316
TI  - Cytomegalovirus.

PMID- 7811317
TI  - Our clients/patients can teach us.

PMID- 7811318
TI  - Graduate programs fall short.

PMID- 7811319
TI  - Acute pancreatitis.

PMID- 7811321
TI  - Role of low-substituted hydroxypropylcellulose in dissolution and bioavailability
      of novel fine granule system for masking bitter taste.
AB  - Coated fine granules with water-insoluble film composed primarily of
      ethylcellulose, containing 20% of sparfloxacin (SPFX) and various amounts of low
      substituted hydroxypropylcellulose (L-HPC) (0-52%) in the cores and which masked
      the bitter taste of SPFX, were orally administered to fasting rats to determine
      the effect of L-HPC on bioavailability. The release of SPFX in water from four
      kinds of these coated fine granules containing 0, 25, 40 and 52% of L-HPC showed
      the pseudo first order kinetics, followed by the second phase, with refractive
      points between 0.25 and 0.5 h. The rate constant (K1) up to 0.25 h increased with
      an increase [corrected] of the amount of L-HPC in the core, and the rate constant
      (K2) in subsequent release (the second phase) was lower than K1 in each fine
      granule. Areas under plasma concentration-time curves (AUC) of SPFX and the peak
      plasma SPFX levels (Cmax) after oral administration of coated fine granules
      lacking L-HPC to fasting rats were suppressed to one-eighth and one-ninth,
      respectively, of those obtained from the core granules that rapidly released
      SPFX. However, AUC and Cmax from the coated fine granules increased linearly with
      an increase in the amount of L-HPC in the cores, and nearly equaled those from
      the core fine granules when the content of L-HPC was 52%. These results confirmed
      that the addition of L-HPC to the cores increases not only the dissolution rate
      but also the bioavailability of SPFX.

PMID- 7811320
TI  - Activation of Raf as a result of recruitment to the plasma membrane.
AB  - The small guanine nucleotide binding protein Ras participates in a growth
      promoting signal transduction pathway. The mechanism by which interaction of Ras
      with the protein kinase Raf leads to activation of Raf was studied. Raf was
      targeted to the plasma membrane by addition of the COOH-terminal localization
      signals of K-ras. This modified form of Raf (RafCAAX) was activated to the same
      extent as Raf coexpressed with oncogenic mutant Ras. Plasma membrane localization
      rather than farnesylation or the presence of the additional COOH-terminal
      sequence accounted for the activation of RafCAAX. The activation of RafCAAX was
      completely independent of Ras; it was neither potentiated by oncogenic mutant Ras
      nor abrogated by dominant negative Ras. Raf, once recruited to the plasma
      membrane, was not anchored there by Ras; most activated Raf in cells was
      associated with plasma membrane cytoskeletal elements, not the lipid bilayer.
      Thus, Ras functions in the activation of Raf by recruiting Raf to the plasma
      membrane where a separate, Ras-independent, activation of Raf occurs.

PMID- 7811322
TI  - ED length-of-stay and illness severity in dizzy and chest-pain patients.
AB  - Emergency department (ED) length of stay, illness severity, and patterns of ED
      based testing can be used to compare different ED patient populations. To assess
      the relative significance of ED patients with dizziness and chest pain in
      emergency medicine practice, the investigators formed a retrospective chart
      review of 3,864 adults (age > or = 16 years) seen at the University of North
      Carolina Hospitals' ED during May and June of 1991. Patients were eligible if
      they had any complaint of dizziness (n = 259), nontraumatic chest pain (n = 168),
      or both (n = 18). ED length of stay and illness severity, as measured by Acute
      Physiology and Chronic Health Evaluation (APACHE) II score, were not
      significantly different between the two groups. Dizzy and chest-pain patients
      were both high users of ED-based testing, but management patterns were different.
      Chest-pain patients were more likely to undergo electrocardiogram and x-ray
      testing, whereas dizzy patients more often received testing such as brain
      computed tomography scanning (10.8% v 3.6%, P = .01). ED patients with dizziness
      and chest pain were similar with regard to ED length of stay. Given their overall
      similarities to the chest-pain group, dizzy patients appear to represent a
      significant population of ED patients and may warrant more clinical study.

PMID- 7811323
TI  - [Utility of the direct culture examination (Ziehl-Neelsen) using the Bactec
      system for the presumptive identification of Mycobacterium tuberculosis complex,
      Mycobacterium avium complex, Mycobacterium xenopi, and Mycobacterium kansasii].
AB  - BACKGROUND: The usefulness of the microscopic examination of Bactec 12B and 13A
      growth medium as a method for the possible identification of M. tuberculosis
      complex, M. avium complex, M. xenopi, and M. kansasii was performed out to guide
      the selection of different genetic identification probes and, in the case of M.
      xenopi, the selection of the temperature of subcultures incubation. METHODS: Upon
      detection of an index of growth greater than 100 in Bactec tubes, staining was
      performed by the Ziehl-Neelsen technique. On the basis of the morphology
      observed, the possible identification was performed by genetic probes.
      Subcultures were used for definitive identification. RESULTS: Three hundred forty
      four positive samples were studied by radiometric technique. A total of 190
      strains were identified as M. tuberculosis, 88 strains as M. avium-intracellulare
      (MAI), 33 strains as M. xenopi, 14 strains as M. kansasii and 19 strains were
      identified as: M. gordonae (10), unpigmented rapid growth microbacteria (7), and
      M. simiae (2). Sensitivity, specificity, positive predictive value, and negative
      predictive value were 97.9%, 95.4%, 96.4%, and 97.3%, respectively for M.
      tuberculosis complex, 84.0%, 99.2%, 97.3% 94.7% for M. avium complex; 63.6%,
      98.3%, 80.7%, 96.2% for M. xenopi; 35.7%, 98.1%, 45.5% 97.2% for M. kansasii.
      CONCLUSIONS: The morphology of M. tuberculosis complex examined in the
      radiometric system in useful to differentiate this species from other
      microbacteria (MOTT), allowing the selection of specific probe used. Within the
      MOTT, M. avium complex also has morphological characteristics which are useful
      for its differentiation, the morphology usually described for the remaining
      species was frequently not observed.

PMID- 7811324
TI  - Effects of music on cardiovascular reactivity among surgeons.
AB  - OBJECTIVE: To determine the effects of surgeon-selected and experimenter-selected
      music on performance and autonomic responses of surgeons during a standard
      laboratory psychological stressor. DESIGN: Within-subjects laboratory experiment.
      SETTING: Hospital psychophysiology laboratory. PARTICIPANTS: A total of 50 male
      surgeons aged 31 to 61 years, who reported that they typically listen to music
      during surgery, volunteered for the study. MAIN OUTCOME MEASUREMENTS: Cardiac
      responses, hemodynamic measures, electrodermal autonomic responses, task speed,
      and accuracy. RESULTS: Autonomic reactivity for all physiological measures was
      significantly less in the surgeon-selected music condition than in the
      experimenter-selected music condition, which in turn was significantly less than
      in the no-music control condition. Likewise, speed and accuracy of task
      performance were significantly better in the surgeon-selected music condition
      than in the experimenter-selected music condition, which was also significantly
      better than the no-music control condition. CONCLUSION: Surgeon-selected music
      was associated with reduced autonomic reactivity and improved performance of a
      stressful nonsurgical laboratory task in study participants.

PMID- 7811325
TI  - An arcane role of DNA in transcription activation.
AB  - The mechanism by which the cAMP receptor protein (CRP) activates transcription
      has been investigated using the lac promoter of Escherichia coli. For
      transcription activation, an interaction between DNA-bound CRP and RNA polymerase
      is not sufficient. CRP must bind to a site in the same DNA and close to the
      promoter. CRP action requires an intact spacer DNA to provide a rigid support in
      building a CRP-RNA polymerase protein bridge or to allow a conformational change
      in the DNA to be transmitted to the lac promoter using the protein bridge as a
      structural support.

PMID- 7811326
TI  - No such thing as nonaccidental injury.

PMID- 7811327
TI  - Benefits of primary care.

PMID- 7811328
TI  - Management of dizziness.

PMID- 7811329
TI  - The kinetics of HIV-1 long terminal repeat transcriptional activation resemble
      those of hsp70 promoter in heat-shock treated HeLa cells.
AB  - The long terminal repeat (LTR) of human immunodeficiency virus type 1 (HIV-1) is
      activated under different conditions including heat shock. By using transient
      transfection assays, we have compared the thermal activation of HIV-1 LTR to that
      of the promoter of the gene encoding the human stress protein hsp70 which is
      under the control of the heat shock transcription factor HSF. In these assays,
      the chloramphenicol acetyl transferase (Cat) gene was used as a reporter gene.
      Several parameters of the heat stress were analyzed such as the temperature, the
      duration of heat stress and that of the recovery period. Under every condition
      tested, we have found that the kinetics of activation of both promoters were very
      similar. In addition, both showed a similar inhibition by actinomycin D. These
      results were compared to those obtained with a DNA construct containing the early
      promoter of SV-40 virus coupled to the Cat gene. In this case, no heat-mediated
      accumulation of CAT protein was observed, indicating that the transcriptional
      activation of HIV-1 LTR by heat shock is specific. HIV-1 LTR contains two NF
      kappa B binding elements, involved in the activation of this promoter during
      oxidative stress, which are sequence related to the heat shock element HSE.
      However, under all the heat shock conditions tested, we have been unable to
      detect the binding of any protein to kappa B elements, suggesting that this site
      is not directly involved in the thermal activation of HIV-1 LTR. These results
      indicate that the thermal transcriptional activation of HIV-1 LTR and hsp70
      promoters occurs through different mechanisms that are triggered by similar heat
      shock conditions.

PMID- 7811330
TI  - Rapid evaluation of ethanol content and metabolism in human plasma using
      quantitative proton magnetic resonance spectroscopy.
AB  - Proton magnetic resonance spectroscopy (MRS) was used to assay ethanol in plasma.
      Ethanol concentrations determined by MRS and conventional enzymatic methods are
      in excellent agreement. In addition to ethanol, acetone, acetate and beta
      hydroxybutyrate can be quantified simultaneously in the same sample. Proton MRS
      of plasma offers a rapid evaluation of human ethanol metabolism and may be useful
      in screening for chronic alcoholism.

PMID- 7811331
TI  - Acute ethanol increases taurine but neither glutamate nor GABA in the nucleus
      accumbens of male rats: a microdialysis study.
AB  - The effects of acute intraperitoneal administration of ethanol (1-3 g/kg body wt)
      on the extracellular concentrations of glutamate (GLU), taurine (TAU) and gamma
      aminobutyric acid (GABA) in rat brain nucleus accumbens were studied by the
      microdialysis technique coupled to HPLC-EC detection. Levels of GLU and GABA were
      not affected by ethanol, whereas those of TAU were increased by doses of the drug
      of 2-3 g/kg.

PMID- 7811332
TI  - 7-OHDPAT and alcohol consumption, withdrawal and discriminative stimulus
      properties in rats.
AB  - A series of experiments was performed, which indicated that 7-OHDPAT is only
      active in rats that are still in the dynamic phase of the development of a high
      and stable level of alcohol preference and in a drug discrimination test
      procedure, but not in rats with a matured preference for 3% alcohol. These data
      may point to a limited use of 7-OHDPAT in conditions of alcohol misuse and
      dependence.

PMID- 7811333
TI  - The validity of the Michigan Alcoholism Screening Test (MAST).
AB  - This review examines the validity of the Michigan Alcoholism Screening Test
      (MAST) as a screening instrument for alcohol problems. Studies that compare the
      MAST-questionnaire with other defined diagnostic criteria of alcohol problems
      were retrieved through MEDLINE and a cross-bibliographic check. A total of 20
      validity studies were included. The studies varied considerably regarding the
      prevalence of alcohol problems, the diagnostic criteria, and the examined patient
      categories. The MAST compared with other diagnostic criteria of alcohol problems
      gave validity measures with the following span: predictive positive value (PVpos)
      0.24-0.96, predictive negative value (PVneg) 0.78- approximately 1, sensitivity
      0.36- approximately 1, and specificity 0.36-0.96. It appears that the PVneg are
      high. Except from one study, the sensitivities (0.57- approximately 1) are also
      high. The PVpos and the specificities show substantial variations. The variables
      that seem to have the largest influence on the PVpos seem to be the prevalence of
      alcohol problems, the diagnostic method against which the MAST-questionnaire is
      validated, and the populations on which the MAST is applied. The MAST should in
      the future be validated against internationally accepted diagnostic methods on
      populations with representative prevalences of alcohol problems.

PMID- 7811334
TI  - Hypothesis: factors involved in the mechanisms regulating food intake affect
      alcohol consumption.
AB  - In addition to being a pharmacological agent, alcohol (ethanol) can also be
      considered a food; the body can utilize effectively its calorific contribution.
      The consumption of alcohol has in many respects the same characteristics as the
      intake of food. In animal experiments, food intake decreases in relation to the
      calorific value of the alcohol consumed; in human studies, various results have
      been obtained from no compensation to full compensation for the contribution from
      alcohol. If a choice is possible, primarily the carbohydrate part of the diet is
      decreased for compensation to ethanol intake. Food, in turn, can influence
      alcohol consumption. There is evidence that it is the carbohydrate content of the
      diet which influences alcohol drinking. The daily intake of alcohol is equally or
      even better regulated than intake of carbohydrate, protein, or fat. There is a
      circadian rhythm of alcohol consumption which resembles the rhythm of food
      intake. However, the mechanism which regulates alcohol intake does not have a
      very strong influence on the behaviour of most animals or humans, and its control
      is often overpowered by outside factors. Nevertheless, it is important to
      identify the precise mechanism because a better understanding should provide
      valuable information for use in the search for risk markers and pharmacological
      treatments for alcoholism.

PMID- 7811335
TI  - Alcohol and antioxidant systems.
AB  - Following the pioneer report of Di Luzio (Physiologist 6, 169-173, 1963)
      concerning the prevention of the acute ethanol-induced fatty liver by
      antioxidants, many observations have shown that ethanol-induced liver injury may
      be linked, at least partly, to an oxidative stress resulting from increased free
      radical production and/or decreased antioxidant defence. The disturbances induced
      in the major hepatic enzymatic and non-enzymatic antioxidant systems following
      experimental acute and chronic ethanol administration are reviewed, emphasizing
      the important role of dietary alpha-tocopherol in modifying the induction of
      oxidative stress and its usual expression as increased lipid peroxidation.
      Adaptative increases in some elements of the hepatic antioxidant defence partly
      counteract the enhanced generation of prooxidant free radicals following chronic
      ethanol intake. By contrast, lipid peroxidation is favoured when ethanol is
      administered together with a fat-rich diet and/or various xenobiotics. Chronic
      ethanol feeding has also been reported to potentiate the oxidative stress
      resulting from an acute ethanol load. By generating potent chemoattractants for
      human neutrophils and/or by stimulating the expression of genes involved in
      collagen biosynthesis, liver lipid peroxidation may play an important role in the
      progression of steatosis to hepatitis and cirrhosis. Oxidative stress has been
      shown not to be restricted to the liver, but also to affect, under some
      experimental conditions of ethanol administration, extrahepatic tissues, such as
      the central nervous system, the heart and the testes. This stress can be partly
      prevented by vitamin E supplementation. Ethanol-induced antioxidant disturbances
      have also been reported in clinical studies in blood and liver biopsies.
      Pharmacological antioxidants could have beneficial effects in reducing the
      incidence of ethanol-induced changes in cellular lipids, proteins and nucleic
      acids. The antioxidants considered could act by reducing free radical production
      (e.g. chelators of redox-active iron derivatives), trapping free radicals
      themselves, interrupting the peroxidation process or reinforcing the natural
      antioxidant defence.

PMID- 7811336
TI  - Contribution of NMR spectroscopy to the biochemical investigation of ethanol
      induced perturbations in hepatic metabolism.
AB  - The potential and versatility of nuclear magnetic resonance (NMR) spectroscopy
      comply ideally with the study of the wide range and complexity of ethanol
      repercussions on hepatic metabolism. The same technique allows investigations on
      various experimental models, ranging from isolated molecules to laboratory
      animals in situ, as well as extending to the clinically relevant examination of
      ethanol-induced pathophysiological disorders in humans. In the present review, we
      document the contribution of NMR spectroscopy to the experimental elucidation of
      the enzymatic pathways of ethanol catabolism in the liver, and the consequences
      of its oxidation on intermediary metabolism using nonradioactive tracer
      molecules, in addition to emphasizing the interactions of ethanol with the energy
      state of the hepatocyte via shifts elicited in the redox state of subcellular
      compartments of the cell. The long-term consumption of excessive quantities of
      alcohol triggers the development of various pathophysiological disorders. We
      therefore discuss the current possibilities for the non-invasive detection and
      characterization of these pathologies on experimental models of intoxicated
      animals, as well as the expectations for a clinical differential diagnosis of
      alcoholic liver diseases in humans by NMR spectroscopy.

PMID- 7811337
TI  - Alcohol consumption by nursing rats and its effect on the cerebellum of the
      offspring.
AB  - To study the effect of alcohol on Purkinje cells and on myelination of the
      cerebellum of neonate rats, female Sprague-Dawley rats were fed alcohol (ethanol)
      during their nursing period. The alcohol was given in amounts of 5% or 10% per
      volume of drinking water. Food and liquids, equal in calories, were distributed
      among dams receiving alcohol. One group of control rats received similar diet but
      no alcohol. The results were then compared with those of a second group of
      controls, receiving no alcohol but having access to unlimited supplies of food
      and water. Histological examination of pups revealed degenerative changes in
      Purkinje cells and delayed myelination of the cerebellum.

PMID- 7811338
TI  - A joint problem drinking clinic: the King's College and Maudsley hospitals
      initiative.
AB  - We describe the establishment of a joint alcohol misuse clinic, staffed by both a
      psychiatrist and a physician, in a London Teaching Hospital providing general as
      well as specialist medical services. The demographic and medicopsychiatric
      problems of the first 100 referrals (60% attendance rate) are described. The
      clinic provides an assessment and re-education role for most patients referred
      with alcohol misuse problems: the need for specialist alcohol treatment
      facilities, especially for in-patients, remains essential. In addition, the
      clinic provides a valuable training and research resource.

PMID- 7811339
TI  - Underage drinking in the United Kingdom since 1970: public policy, the law and
      adolescent drinking behaviour.
AB  - This paper is concerned with underage drinking in the United Kingdom since 1971
      and public policy relating to this issue. Research into youthful drinking and the
      relevant licensing laws are summarised. Data obtained from surveys and from
      statistics relating to offences against the licensing laws are presented, which
      together illustrate the difficulty in enforcing this legislation. It is concluded
      that there is no evidence that 'underage' drinking has either increased or
      decreased over the past 20 years, and that the criminal statistics give little
      indication of the regularity with which the licensing legislation is breached.
      Reasons for this include difficulty in assessing the age of young people and the
      complicated nature of the licensing laws.

PMID- 7811341
TI  - Cholecystokinin receptor binding after long-term ethanol treatment in rats.
AB  - Brain cholecystokinin (CCK) receptors have been implicated in anxiety disorders
      and suicidal behaviour. We have examined the radioligand binding ability of CCK
      and benzodiazepine receptors in rat brain after long-term intermittent voluntary
      vs voluntary and forced low-dose ethanol exposure. During 58 weeks, one group of
      rats had a choice between ethanol and water as the drinking fluid for 24 hr each
      week. Another group of rats had the same weekly choice between ethanol and water,
      but at the end of each 24 hr choice period, ethanol (2.0 g/kg) was injected.
      During the second period of ethanol treatment, lasting for 32 weeks, both ethanol
      treated groups had continuous free access to ethanol and water. These two
      treatments have previously been shown to induce partially different neurochemical
      alterations. In the present investigation, benzodiazepine receptor binding in the
      frontal cortex, hippocampus and striatum was similar in both ethanol treatment
      groups compared to controls. CCK receptor binding in the hippocampus and striatum
      did not differ between the three groups; however, in the frontal cortex, there
      was an increase in the apparent number of CCK binding sites in the group of rats
      submitted to voluntary plus forced ethanol exposure as compared to the control
      group or the voluntary intake group. These results suggest that long-term ethanol
      treatment may lead to alterations in brain CCK-ergic neurotransmission, but that
      the changes are specific to the treatment schedule.

PMID- 7811340
TI  - Lipid peroxidation and ethanol-related tumor promotion in Fischer-344 rats
      treated with tobacco-specific nitrosamines.
AB  - Male Fischer-344 rats were treated, by gavage, with a total dose of 40 mmol/kg of
      N'-nitrosonornicotine (NNN) or 20 mmol/kg of 4-(methylnitrosamino)-1-(3-pyridyl)
      1-butanone (NNK), three times a week for 4 weeks. One week afterwards the rats
      were fed an isocaloric liquid diet containing 7% (v/v) ethanol and continued on
      this diet until killed. Cumulative ethane exhaled by a rat by 180 min was
      measured at 54 weeks of the start of the study and was found to increase
      significantly (P < 0.001) with either NNN or NNK treatment but more so when
      followed by ethanol consumption. Other indices of lipid peroxidation, cholesterol
      and phospholipids were measured in the lipid extracts from the liver, esophagus
      and lungs at 55 weeks. Ethanol consumption increased the amount of cholesterol
      and phospholipids per g of tissue in naive or NNN- and NNK-treated rats. All
      peroxidative indices measured, i.e. malondialdehyde (MDA), diene- and triene
      conjugates and lipid fluorescence, were significantly increased in the liver, the
      main metabolic and peroxidative site, with ethanol consumption in rats whether
      they were treated with NNN or NNK or remained untreated. Overall, the indices of
      lipid peroxidation also showed an increase in other tissues, but the results
      differed with different indices. The differences in indices may be due to
      differences in lipid peroxidation products measured or to differences in their
      rates of production and degradation or conversion to other products. However, the
      largest increases in indices were seen with ethanol consumption by either NNN- or
      NNK-treated rats. Incidence of tumors in the tissues was also assessed and showed
      about a two-fold increase with ethanol consumption in the tumors of esophagus,
      oral cavity, lungs and liver induced by either NNN or NNK. Ethanol also caused an
      increase in the mean frequency and mean size of the tumors induced. The results
      suggest that ethanol-related promotion of NNN- and NNK-induced tumors may result
      from increased lipid peroxidation in the target tissue.

PMID- 7811342
TI  - Prevalence of alcohol problems among adult somatic in-patients of a Copenhagen
      hospital.
AB  - The adult patients of somatic departments of a Copenhagen hospital were screened
      on a randomly selected day during a 14 day period by interviewers who examined
      them using a structured questionnaire regarding life-style. A patient was
      considered having an alcohol problem if one or more of the following criteria was
      fulfilled: (1) a self-reported daily alcohol consumption for at least 2 years of
      at least 60 g of ethanol in men and 36 g in women, (2) a Michigan Alcoholism
      Screening Test (MAST) score of or above 5, (3) an alcohol-related discharge
      diagnosis. In total, 692 patients fulfilled the entry criteria, but 181 patients
      (26.2%) had to be excluded owing to predefined exclusion criteria (terminal
      illness, dementia, etc.), and 74 patients (14.5%) refused to participate. Among
      the 437 interviewed patients, 125 patients (28.6%; 95%-confidence limits 24.4
      33.1%) fulfilled one or more of the diagnostic criteria for an alcohol problem.
      Only 14 patients (3.2%; 95%-confidence limits 1.8-5.3%) had an alcohol-related
      discharge diagnosis. The prevalence of patients with alcohol problems was
      significantly (P < 0.05) higher among male patients (82 of 171 men (48.0%; 95%
      confidence limits 40.3-55.7%)) than among female patients (43 of 266 women
      (16.2%; 95%-confidence limits 12.0-21.2%)). The prevalence of patients with
      alcohol problems was 32.4% (95%-confidence limits 25.5-39.8%) in internal
      medicine departments, 28.5% (95%-confidence limits 21.3-36.6%) in surgical
      departments, and of female patients 22.2% (95%-confidence limits 13.7-32.8%) in
      the department of gynaecology and obstetrics.

PMID- 7811343
TI  - Drinking habits of medical students call for better integration of teaching about
      alcohol into the medical curriculum.
AB  - A study was conducted with medical students to observe their drinking habits and
      alcohol misuse. The students completed questionnaires composed of AUDIT and SMAST
      questions. A significant proportion (33%) of students drank more than the
      recommended safe limit and screened positive at the AUDIT cut-off score of 11.
      The high scores of DSM-III criterion questions indicate that problem drinking on
      college campuses continues to be a significant public health concern. Our opinion
      is that prevention of alcohol misuse should be started at medical universities.
      The medical school curriculum must integrate education about alcohol. First the
      attitude of medical professionals should be changed so that we can achieve
      results in alcohol misuse prevention in society as a whole.

PMID- 7811344
TI  - Effect of S-adenosyl-L-methionine administration on red blood cell cysteine and
      glutathione levels in alcoholic patients with and without liver disease.
AB  - We measured glutathione and cysteine concentrations in erythrocytes of chronic
      alcohol misusers with (20 subjects) and without liver cirrhosis (20 subjects).
      Glutathione levels were decreased, whereas those of cysteine were increased in
      all patients. Parenteral treatment with S-adenosylmethionine (SAME); (2 g daily
      in 250 ml 0.15 M NaCl for 15 days) corrected the erythrocyte thiol alterations.
      We conclude that parenteral treatment with SAME affects the metabolism of SH
      compounds in erythrocytes of alcoholic patients.

PMID- 7811345
TI  - Malondialdehyde stimulates collagen production by hepatic lipocytes only upon
      activation in primary culture.
AB  - Lipid aldehydes have been proposed as mediators of hepatic fibrosis in
      alcoholics. In this study we examined whether hepatic lipocytes, the principal
      matrix-producing cells in liver, exhibit enhanced collagen synthesis in response
      to the lipid aldehyde malondialdehyde. Lipocytes isolated from normal rat liver
      and plated in primary culture for 3 days were not affected by malondialdehyde in
      concentrations ranging from 2 to 200 microM. Cells cultured for 7 days displayed
      a modest increase in collagen synthesis (137% of control levels) in response to
      malondialdehyde, but only at a concentration of 200 microM. The malondialdehyde
      induced increase in collagen synthesis was paralleled by a rise in type I
      procollagen mRNA. Subcultured rat fibroblasts at confluent density responded
      better to malondialdehyde than did 7-day lipocytes. The results indicate that
      lipocytes respond to the fibrogenic effects of malondialdehyde only after
      activation in primary culture. This delayed response suggests that lipid
      aldehydes may enhance, but do not initiate, alcoholic liver fibrosis in vivo.

PMID- 7811346
TI  - Alterations of neocortical neuronal responses to acetylcholine and GABA in rats
      born to alcohol-dependent mothers.
AB  - Alcohol is known to be a CNS teratogenic factor interfering with neuronal and
      synaptic maturation. The purpose of this microiontophoretic study was to explore
      GABAergic and cholinergic central mechanisms in adult rats exposed to alcohol in
      the third phase of prenatal life (ADM), when their mothers were subjected to
      alcohol physical dependence induction (9.6 g/kg/day). Responses to acetylcholine
      and GABA were recorded in frontal and somatosensory cortical neurons. Adult rats,
      whose mothers had been administered placebo with identical procedures, were used
      as a control (C). Cholinergic responses were significantly decreased and
      GABAergic responses increased in ADM animals with respect to controls. After a
      single i.p. alcohol injection (1.6 g/kg) spontaneous firing was depressed in ADM
      animals to a lesser extent than in C rats. Cholinergic excitations were reduced
      in C group and potentiated with reversal of atropine antagonism in ADM animals.
      GABAergic inhibitions were slightly increased and bicuculline antagonism was
      blocked in C rats, while ADM animals showed decreased responses to GABA. The
      present results support the hyperactivity of GABAergic system and the
      hypoactivity of cholinergic system reported in previous studies on prenatally and
      postnatally alcohol-exposed animals. Microiontophoretic results following ethanol
      injection led to the hypothesis that a rapid tolerance/dependence may develop in
      the offspring of alcohol-dependent rats.

PMID- 7811347
TI  - 3,5-Diphenyl-1H-pyrazole derivatives. XII. N-substituted 4-amino-1-(2-hydroxy- or
      2-alkylaminoethyl)-3,5-diphenyl-1H-pyrazoles with local anesthetic, analgesic and
      platelet antiaggregating activities.
AB  - The synthesis of 4-amino-3,5-diphenyl-1H-pyrazole-1-ethanol, as well as of their
      N-methyl, N-ethyl and N,N-dimethyl derivatives is described. A series of 1-(2
      alkylaminoethyl)-3,5-diphenyl-1H-pyrazole-4-amines and of N-substituted 4
      dimethylamino-3,5-diphenyl-1H-pyrazole-1-ethanamines were also prepared. Some of
      the above compounds showed remarkable local anesthetic, analgesic and in vitro
      platelet antiaggregating activities, as well as moderate antiinflammatory and
      antipyretic activities in rats and mice.

PMID- 7811348
TI  - 5-[[omega-(Dialkylamino)alkoxy]methylene]-1,3,3-trimethyl-2- oxabicyclo
      [2.2.2.]octan-6-ones with hypotensive, local anesthetic, antiarrhythmic and other
      activities.
AB  - The synthesis of 5-[[omega-(dialkylamino)alkoxy]methylene]-1,3,3-trimethyl-2-
      oxabicyclo[2.2.2]octan-6-ones by reaction of (+)-5-(hydroxymethylene)-1,3,3
      trimethyl-2-oxabicyclo[2.2.2]octan- 6-one with a series of omega
      (chloroalkyl)dialkylamines in the presence of potassium carbonate is described.
      Some compounds showed strong hypotensive, local anesthetic and antiarrhythmic
      activity in rats and mice, as well as moderate analgesic, antipyretic and in
      vitro platelet antiaggregating activity.

PMID- 7811349
TI  - O-[omega-(Dialkylamino)alkyl]oximes of (+)-1,7,7-trimethylbicyclo [2.2.1]heptan-2
      one with hypotensive, antiinflammatory, analgesic, local anesthetic and other
      activities.
AB  - The synthesis of (+)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-one O-[omega
      (dialkylamino)alkyl]oximes by reaction of (+)-camphoroxime sodium salt with a
      series of omega-(chloroalkyl)dialkylamines in DMF solution is described. Some of
      the above compounds showed strong hypotensive, antiinflammatory, analgesic and
      local anesthetic activity in rats and mice, as well as moderate antiarrhythmic,
      antipyretic and in vitro platelet antiaggregating activity.

PMID- 7811350
TI  - 5-Substituted 2,3-dihydro-6-mercapto-1,3-diphenyl-2-thioxo-4(3H)-pyrimidinones
      and their 6-(acylthio) derivatives with platelet antiaggregating,
      antiinflammatory, antiarrhythmic, antihyperlipidemic and other activities.
AB  - The synthesis in excellent yields of 2,3-dihydro-6-mercapto-1,3,5-triphenyl-2
      thioxo-4(3H)-pyrimidinone 3 and 5-ethoxycarbonyl-2,3-dihydro-6-mercapto-1,3
      diphenyl-2-thioxo-4(3H )- pyrimidinone 4 by reaction of methyl phenylacetate or
      diethyl malonate, respectively, with phenyl isothiocyanate (3 molar equivalents)
      and sodium hydride (2 molar equivalents) in DMF solution is described. Acylation
      of 3 and 4 with acyl chlorides gave, generally in satisfactory yields, 6-acylthio
      derivatives 13 and 14. Some of the above compounds showed a platelet
      antiaggregating activity in vitro superior or comparable to that of
      acetylsalicylic acid, as well as remarkable antiinflammatory, antiarrhythmic,
      local anesthetic and antihyperlipidemic activities in rats and in mice. Weak
      anticonvulsant and hypoglycemic activities were also detected.

PMID- 7811351
TI  - Synthesis and pharmacological activities of ethyl 5-cyano-1,6-dihydro-6-oxo-2
      (2,3,4-pyridyl)-3-pyridinecarboxylates and derivatives.
AB  - The synthesis of ethyl esters of 5-cyano-1,6-dihydro-6-oxo-3-pyridinecarboxylic
      acids carrying as 2-substituent the 2-,3- or 4-pyridyl group is described. By
      alkaline hydrolysis followed by acidification, these esters gave the
      corresponding carboxylic acids, which were decarboxylated to 1,2-dihydro-2-oxo-6
      (2,3,4-pyridyl)-3-pyridinecarbonitriles. As milrinone analogues, the above
      compounds were tested on contractile activity and frequency rate of spontaneously
      beating atria from reserpine-treated guinea-pigs. Ethyl 5-cyano-1,6-dihydro-6-oxo
      2-(2-pyridyl)-3-pyridinecarboxylate showed an appreciable positive inotropic
      activity, although inferior to that of milrinone; moreover, some other compounds
      bearing the above 2-substitution pattern showed interesting antiinflammatory,
      analgesic and hypotensive activity.

PMID- 7811352
TI  - 5-HT and DA receptor affinity of arylpiperazine derivatives with terminal
      benzamide fragment.
AB  - The synthesis of some arylpiperazines with a benzamide moiety on N-4 alkyl chain
      was accomplished and their dopaminergic and serotonergic affinity was assayed by
      in vitro receptor binding. The results of such investigation showed a moderate
      affinity on D-2 receptors and a lack of 5-HT receptor affinity.

PMID- 7811353
TI  - Molecular properties of the WB4101 enantiomers and of its chiral methyl
      derivatives for alpha 1-adrenoceptor recognition.
AB  - The optical isomers of the well known alpha 1-antagonist WB4101 and of its
      derivatives with a methyl group in the oxyethyl moiety were prepared for the
      evaluation of their alpha-adrenoceptors binding affinity. By means of a detailed
      computational analysis, the present work shows that the introduction of a methyl
      group affects the behaviour of WB4101 in different ways. A limitation of the
      conformational freedom in certain regions of the torsional subspace of the
      potential energy function, differences in the reactivity of the protonated
      species towards a model proton acceptor and the quality of the superposition with
      the rigid template for alpha 1 antagonists, corynanthine, are examined and
      discussed in order to select a candidate bioactive form and possible features
      which act as modulators of the recognition process at the alpha 1-adrenoceptors.

PMID- 7811354
TI  - Ab initio studies of hydrogen bonds: the water dimer paradigm.

PMID- 7811355
TI  - Laser desorption and ejection of biomolecules from the condensed phase into the
      gas phase.

PMID- 7811356
TI  - Vibrational relaxation dynamics in solutions.

PMID- 7811357
TI  - Solid-state NMR structural studies of proteins.

PMID- 7811358
TI  - [A review of the polymorphism of biological characteristics in medicinal plant
      seeds].

PMID- 7811359
TI  - [Studies of resources and production of fructur Mume].

PMID- 7811360
TI  - [Application of cluster analysis to chemical identification of the drugs from
      fruits of Zingiberaceae].
AB  - The present paper deals with an application of cluster analysis to the chemical
      identification of the drugs from fruits of Zingiberaceae. Thirty numerical
      characters were obtained from thin layer chromatograms of volatile oils and
      flavonoids. The coefficient of Seuclid was used to show quantitative index of
      similarities among the samples. By methods of systematic cluster, 4 dendrograms
      from each method were created respectively. The results show that the fruit drugs
      from Amomum are similar to each other, but different from those from Alpinia; the
      results from median method are in accordance with the classification of fruit
      drugs from Zingiberaceae by their traditional effects. This paper may be helpful
      in seeking new resources as well as in identifying the fruit drugs from
      Zingiberaceae.

PMID- 7811361
TI  - [Studies on the soils for growth of Coptis chinensis Franch].

PMID- 7811362
TI  - [Studies on immobilization of suspension cells of peltate yam (Dioscorea
      zingiberensis C.H. Wright)].
AB  - The suspension cells of D. zingiberensis were immobilized with 3% sodium
      alginate, and then cultured in MS+2, 4-D1.0 + 6-BA 0.1 at 25 degrees C for a long
      period of time. The culture fluid free from cells was extracted and analyzed by
      TLC. The result showed that the immobilized cells could secrete the main
      component of D. zingiberensis--diosgenin, but not consecutively.

PMID- 7811363
TI  - [Mildewproof of Chinese traditional medicinal materials].
AB  - A study on the anti-mold activity of BCM, cinnamaldehyde and clove oil, was made
      by means of ultramicrostructural observation. The results show that both
      cinnamaldehyde and clove oil have strong anti-mold activity, (the former being
      even stronger), while BCM works well only in cases of Aspergillus, Penicillium
      and Trichoderma. SME and TME have found out that cinnamaldehyde is able to
      destroy the wall of fungal cells, the coagulate plasma and dissolve the cell
      organs.

PMID- 7811366
TI  - [Degradation of the constituents in solubilization process of donkey skin].
AB  - Dry donkey skin, defatted in advance with hair scraped off, was separately
      solubilized by heating in sealed tubes at 130 degrees C for 2, 4, 6, 8h. The
      resultants were clarified and dried as Ejiao, whose yield appeared to reach
      maximum after 4h heating. Absorptivities of all four Ejiao preparations were in
      good approximation to standard gelatin. However, their intrinsic viscosity
      declined in order of prolonged solubilization process, indicating that
      depolymerization of donkey skin gelatin had taken place. In addition, significant
      degradation of dermatan sulfate, another constituent of Ejiao, was detected
      electrophoretically and photometrically.

PMID- 7811365
TI  - [Analytical study on processing of Rheum palmatum L. by HPLC].
AB  - This paper deals with the effect of processing on Rheum palmatum. A HPLC method
      for the determination of rhein in the drug processed five different ways has been
      established. The method is simple, specific and accurate. The recovery is 98.52%
      and relative standard deviation.

PMID- 7811364
TI  - [The effect of Pinellia processed by ginger juice on gastric and intestinal
      function of animals].
AB  - The experimental research has shown that neither pinellia processed by ginger
      juice and alum nor pinellia boiled by ginger juice have any marked influence on
      the secretion of PGE2 in rat gastric juice, or on the activity of gastric
      proteinase in rats. Both the processed products of pinellia can obviously inhibit
      the gastric and intestinal motility in mice. Raw pinellia can strongly inhibit
      the secretion of PGE2, gastric acidity and gastric proteinase in rats, but acts
      not so heavily on their gastric secretion and appears rather harmful to the
      gastric mucosa in rats. Raw pinellia can also obviously accelerate the gastric
      and intestinal motility in rats.

PMID- 7811367
TI  - [Relationship between three extracting factors and extracting rate and stability
      of chlorogenic acid in the refining process of flos Lonicerae].
AB  - Content determination of chlorogenic acid in the extract of Flos Lonicerae by
      reversed-phase HPLC has proved that relatively long time boiling in weak acid
      conditions is beneficial to increasing the extracting rate of the acid. Also,
      verifying experiments have shown that chlorogenic acid remains stable in the
      above-said conditions.

PMID- 7811368
TI  - [Chemical constituents of Aralia decaisneana Hance].
AB  - Six compounds were isolated from the root bark of Aralia decaisneana and
      elucidated by spectral and chemical analyses as 3-O-[beta-D-galactopyranosyl-(1-
      >4)-beta-D-galactopyranosyl- (1-->3)-beta-D-glucuronopyranosyl]-oleanolic acid
      (Ad-V), chikusetsusaponin IVa (Ad-IX), deglucose chikusetsusaponin IVa (Ad-X),
      palmitic acid (Ad-VI), beta-sitosterol (Ad-VII) and oleanolic acid (Ad-VIII). Ad
      V was obtained from nature for the first time, and the rest were all obtained
      from this plant for the first time.

PMID- 7811369
TI  - [Determination of yuanhuacine in Daphne genkwa Sieb. et Zucc. by HPLC].
AB  - Separated on phenox RP18 column with a mobile phase of methyl alcohol-water
      (82:18) and detected at wavelength 232nm, yuanhuacine has shown a good linearity
      in the range from 7.6 x 10(-3) to 0.76 microgram. The recovery is 99.56% with RSD
      3.61% (n = 9). The content of yuanhuacine in Daphne genkwa is 0.00848%.

PMID- 7811370
TI  - [Comparison between pharmacologic actions of rabbit bile and bear bile].
AB  - In our experiment it was observed that many pharmacologic actions of the rabbit
      bile were similar to those of bear bile. It was also demonstrated that the
      effects of the rabbit bile were more obvious than those of bear bile in positive
      inotropic action, sedation, antitussive action, antihistaminic action and so on.

PMID- 7811371
TI  - [Effect of essential oil of the stem cortex of Acanthopanax giradii Harms on the
      biological activity in human leukaemia cells (K562)].

PMID- 7811372
TI  - [Anti-hypoxia and anti-glucose deficiency effects of PQS on guinea pig papillary
      muscle in low frequency electrical stimulation].
AB  - Panax quinquefolium saponin (PQS) increases the contractibility of papillary
      muscle of guinea pigs during electrical stimulation with frequency of 1/8-1/64Hz
      (P < 0.05). In Krebs-Henseleit solution purged with gas containing 95% N2 and 5%
      CO2 regardless of containing glucose or not, PQS (0.3mg/kg) has the effect of
      anti-hypoxia and anti-glucose deficiency (P < 0.05, P < 0.01) in the electrical
      stimulation with frequency of 1/8-1/64Hz.

PMID- 7811373
TI  - [Anti-virus effect of aralosides].
AB  - The result showed that the anti-virus effect of aralosides on infections with
      poliovirus II, ECHO delta virus, adenovirus II, herpes simplex virus I, coxsackie
      B3 virus and coxsackie A16 virus was remarkable. Aralosides could inhibit the
      development of cytopathic effect (CPE) and protect cultural cells from being
      infected with the above viruses.

PMID- 7811374
TI  - [Inorganic element analysis on different compatibility of sini decoction].
AB  - Thirteen kinds of inorganic elements in Sini decoction with different
      compatibility were analysed by atomic absorption spectrophotometry. The change in
      quantity and kind of medicines has no obvious effect on each element. But the
      extraction rate is reduced according to the increase in quantity and herb
      medicines in the prescription.

PMID- 7811375
TI  - Epidemiological evidence for the impact of whole grains on health.
AB  - Current dietary advice suggests consumers increase consumption of whole-grain
      products because of their potential role in prevention of chronic disease. Whole
      grains are important sources of nutrients that are in short supply in our diet,
      including dietary fiber, resistant starch, trace minerals, certain vitamins, and
      other compounds of interest in disease prevention, including phytoestrogens and
      antioxidants. Despite dietary recommendations to increase intake of whole grains,
      little epidemiological evidence is available to support the physiological
      importance of whole-grain intake. Most epidemiological studies focus on
      nutrients, rather than whole foods, so little attempt has been made to evaluate
      the contribution of whole grains in disease. Further, studies on vegetarians that
      show decreased risk of degenerative diseases are unable to separate the
      contribution of fruit and vegetable intake when compared with whole-grain intake
      and protection from disease. The few epidemiological studies that have evaluated
      a role for whole grains suggest that they have an important role in disease
      prevention and deserve more study.

PMID- 7811376
TI  - Dietary patterns vs. dietary recommendations: identifying the gaps for complex
      carbohydrate.
AB  - Dietary guidelines of the U.S. and Canada recommend that 55% of dietary calories
      of individuals should come from carbohydrates, especially complex carbohydrates.
      However, they generally fail to describe how much should come from complex
      carbohydrates. Undoubtedly, this is because of confusion about the composition of
      complex carbohydrate foods and incomplete knowledge of the health benefits of all
      components of grain products. With the intent of shifting dietary food selection
      to increase carbohydrate consumption above the current 46% of calories, food
      guides recommend 5 to 12 servings per day from grain products. Current estimated
      intake for adults is between four to five servings of grain products, of which
      less than one is from whole grain, in an average 2000-kcal adult diet. To follow
      the advice of the U.S. Food Guide Pyramid, which suggests half the bread (grains)
      group should be whole-grain products, adult Americans should increase their
      intake of whole-grain products four- to fivefold and double their intake of total
      grain products.

PMID- 7811377
TI  - Achieving dietary recommendations: whole-grain foods in the Food Guide Pyramid.
AB  - The Food Guide Pyramid illustrates USDA's food guide developed to help people
      follow the Dietary Guidelines for Americans. Unlike earlier food guides, the new
      food guide specifies foods for a total diet; that is, it addresses both concerns
      about adequacy and moderation. The food guide recommends increased intakes of the
      vegetable, fruit, and grain groups with special emphasis on dark-green leafy
      vegetables, legumes, and whole-grain products. These foods are important sources
      of several vitamins and minerals, complex carbohydrates, and dietary fiber, and
      they are generally low in fat. Analyses of expected nutrient levels provided by
      the food guide diet patterns indicate that the nutrient contribution of whole
      grain products is particularly important for diets at lower calorie levels. In
      these diets, it is recommended that at least half the number of servings in the
      grain group be whole-grain products. In all diets, it is recommended that several
      servings of whole-grain products be included each day. Average intakes of
      vegetables, fruits, and grain products are less than recommended. The pyramid
      graphic has been especially helpful in emphasizing to the public the importance
      of increased consumption of vegetables, fruits, and grain products for a
      healthful diet.

PMID- 7811378
TI  - Optimizing the diet with whole grains.
AB  - Dietary recommendations may be perceived by the general population as causing a
      shift to less food and perhaps to less aesthetically pleasing foods often
      resulting in noncompliance. Technology can play a key role in this scenario by
      creating new formulated foods as well as by utilizing technology to modify whole
      foods or foods containing whole foods and enhancing both their health benefits
      and acceptability. At present we have evidence for a positive role in health of
      nutrients and many nonnutrients in foods, such as whole grains. However, all the
      linkages between dietary components and disease are not clear. Therefore, it is
      critical to design not only appealing formulated foods, but to also ensure
      adequate consumption of whole foods in order to obtain those compounds we know to
      be linked to good health, as well as those yet-unknown compounds or interactions
      in food that are also linked to good health. In all cases, the technical and
      functional properties of food, as well as the nutritional, must be considered in
      order to optimize acceptability and assist in achieving compliance in meeting
      dietary recommendations.

PMID- 7811379
TI  - Antioxidants and hormone-mediated health benefits of whole grains.
AB  - Lignans and phytoestrogens have been associated with protective effect against
      hormone-related diseases, for example, cancer of the breast and prostate, and
      potential mechanisms for this effect have been reported. Antioxidants also appear
      to have some protective effect against diseases associated with reactive free
      radicals such as coronary heart disease and cancer. Whole grains contain some of
      these substances particularly the mammalian lignan precursors, vitamin E, other
      phenolic compounds, Se, and phytic acid. These substances may in part be
      responsible for the reduced risk of cancer and coronary heart disease associated
      with intake of high-fiber diets containing whole grains. Because they are more
      associated with the fiber in the outer layers of the grain, the intake of whole
      vs. refined grain is emphasized for optimum health benefits.

PMID- 7811380
TI  - Whole grains--impact of consuming whole grains on physiological effects of
      dietary fiber and starch.
AB  - Much of the present research on the physiological effects of dietary fiber and
      starch has been done on sources isolated from the parent material, and it is not
      clear whether they have the same effects if fed in the intact or whole grain. For
      dietary fiber, physiological effect depends on extent of fermentation in the
      large intestine, and this is influenced by chemical composition, solubility,
      physical form, and presence of lignin or other compounds. All of these factors
      are altered by isolation of a fiber source from the whole grain, and hence
      effects of eating fiber vary. Similarly, physical form and presence in the whole
      grain will affect digestibility of starch in the small intestine, which in turn
      influences the glycemic response and colonic effects determined by the extent of
      malabsorption and entry into the colon. Starch that enters the colon is fermented
      and produces short-chain fatty acids, particularly butyrate, which is necessary
      to maintain a healthy mucosa. Hence, their presence within the whole grain may
      have important implications for health for both dietary fiber and starch.
      Evidence indicates that such effects are beneficial and that whole-grain
      consumption should be encouraged.

PMID- 7811381
TI  - Narrowing the gap: practical strategies for increasing whole-grain consumption.
AB  - Overcoming consumer confusion and doubt regarding nutrition recommendations is
      key to communicating the message to increase whole-grain foods in the diet.
      Nutrition communicators may do that more successfully by using four tactics to
      fashion messages about whole grains: (1) present a positive message; (2) keep it
      short and simple; (3) keep the message practical and flexible; (4) speak with a
      united voice. The quantitative recommendation to eat at least three servings of
      whole-grain foods daily also must be integrated into national nutrition
      documents, such as Healthy People 2000, Dietary Guidelines for Americans, the
      Food Guide Pyramid, Nutrition Recommendations for Canadians, and Canada's Food
      Guide to Healthy Eating, if we are to be truly successful in communicating the
      need to increase whole-grain consumption.

PMID- 7811382
TI  - Extrachromosomal eukaryotic DNA substrates for switch recombination: analysis of
      isotype and cell specificity.
AB  - Switch recombination in B lymphocytes is a complex process directed by signals
      provided by cytokines and/or TH cells. To analyze these signals in an in vitro
      system, we have developed extrachromosomal eukaryotic substrates for switch
      recombination that replicate autonomously in murine cells and present pairs of
      switch (S) regions in an accessible mode. Switch recombination within the S
      regions results in the expression of the selectable neo gene. The results
      presented here indicate that substrates containing either S mu and S gamma 2b, S
      mu and S gamma 2a, or S mu and S alpha undergo switch recombination with similar
      frequencies in the pre-B-cell line 18-81, which has been previously reported to
      specifically switch to IgG2b. This indicates that, rather than expressing a gamma
      2b isotype-specific recombinase, the 18-81 cells express a switch recombinase
      capable of acting on any accessible S region, supporting the accessibility model.
      The extrachromosomal substrates were rearranged in the 18-81 cells, but not in
      murine myeloma, T-cell, or fibroblast cell lines, supporting the idea that switch
      recombination is indeed regulated in a cell- and developmentally specific manner.
      Restriction enzyme analysis of the plasmid DNA recovered from the selected cell
      lines suggested multiple recombinational events, with most patterns in agreement
      with deletions within one or both switch regions.

PMID- 7811383
TI  - The mouse homeoprotein mLIM-3 is expressed early in cells derived from the
      neuroepithelium and persists in adult pituitary.
AB  - LIM-homeodomain proteins are important in cell lineage specification and possibly
      mediate transcriptional processes in eukaryotes. During the screening of a mouse
      pituitary cDNA library, we isolated a partial cDNA coding for a novel gene
      product that exhibited a predicted amino-terminal sequence similar to the
      homeobox of LIM-homeodomain-containing proteins. Reverse transcriptase-polymerase
      chain reactions (RT-PCR) performed on mouse pituitary mRNA using degenerate
      oligonucleotides based on the conserved LIM-domain sequences, allowed the
      extension of the 5' end of the sequence. The composite 2.2-kb cDNA structure
      predicts a 400-amino-acid-long novel mouse (m) protein, called mLIM-3. This name
      was chosen since within the 59-amino-acid homeodomain, it exhibits 97% sequence
      identity to a recently reported Xenopus homologue xLIM-3. The gene coding for
      mLIM-3 maps to the murine chromosome 2, most probably within the 2B band. Based
      on sequence characteristics, we suggest that LIM-3 belongs to a distinct
      subfamily of LIM-containing homeoproteins. Ontogeny studies using in situ
      hybridization demonstrated that mLIM-3 transcripts can be detected on embryonic
      day 11 (e11) in the primordium of the hypophysis. Following a maximum between e12
      and e14, lower levels persisted into adulthood, where mLIM-3 was expressed
      primarily in the anterior and intermediate lobes of the pituitary. These results
      were confirmed by Northern blot analysis in adult mice which revealed a 2.4-kb
      pituitary mRNA transcript. mLIM-3 transcripts were also detected in pituitary
      cell lines such as the somatotrophs GH3 and GH4C1, the gonadotroph alpha T3-1,
      and the corticotroph AtT-20 cells, but not in 20 other cell lines derived from
      peripheral, endocrine, and neural tissues. Starting from e11, we also observed a
      transient expression of mLIM-3 in the ventral part of the spinal cord, pons, and
      medulla oblongata, reaching a maximum at e13 and from p7 onward, the expression
      of this transcript is no longer detectable. mLIM-3 is also expressed in the
      pineal gland with high levels observed at e20. These data suggest a potential
      role for mLIM-3 in the transcriptional regulation of certain genes during
      morphogenesis and/or maintenance of the differentiated state of the pituitary,
      motor neurons, and pineal gland.

PMID- 7811384
TI  - Identification and characterization of a vitamin D3 response element of chicken
      carbonic anhydrase-II.
AB  - 1,25-Dihydroxyvitamin D3 (VD) controls multiple aspects of homeostasis, cell
      growth, and differentiation by the action of its nuclear receptor (VDR), which
      binds to, and activates transcription from, response elements in the promoter
      region of its target genes. Carbonic anhydrase-II (CA-II), an enzyme important to
      osteoclast function, has been shown to be regulated by VD. We screened the
      promoter of chicken CA-II for VDR binding sites and identified a functional VDRE,
      between positions -1,203 and -1,187. Like the majority of the VDREs described to
      date, this response element consists of two directly repeated hexameric core
      binding motifs spaced by three nucleotides and is bound by a heterodimer formed
      by the VDR and the retinoid X receptor (RXR). We show that the polarity of the
      binding of this heterodimer is 5'-VDR-RXR-3' in the CA-II VDRE, whereas on a
      "classical" DR3-type VDRE, such as that of the mouse osteopontin gene, this
      polarity is reversed to 5'-RXR-VDR-3'. We also show that the polarity of the
      heterodimeric complex in relation to the basic transcriptional machinery
      influences the sensitivity of the transcriptional activity to VD. This suggests
      that the orientation of a hormone response element in its natural promoter
      context constitutes an additional level of gene regulation.

PMID- 7811385
TI  - Role of hepatocyte growth factor in breast cancer: a novel mitogenic factor
      secreted by adipocytes.
AB  - Stromal cells can dramatically affect the growth and metastatic capability of
      breast carcinoma cells. Growth factors, considered to be important mediators of
      this process, act as either mitogenic or mito-inhibitory regulators. We have
      developed an in vitro coculture system to examine the influence of adipocytes, a
      dominant mammary stromal cell type, on the growth of a murine mammary carcinoma,
      SP1. Previously, we have reported that conditioned medium (CM) from 3T3-L1
      adipocytes can promote in vitro growth of SP1 cells. We now show that the major
      mitogenic signal derived from 3T3-L1 adipocyte CM is mediated by hepatocyte
      growth factor (HGF). Neutralizing antibody against HGF at 15 micrograms/ml
      completely abrogated mitogenic activity of 3T3-L1 CM. Furthermore, heparin, an
      inhibitor of biological activity of HGF, inhibited the mitogenic activity of 3T3
      L1 CM. Western blot analysis also confirmed the presence of HGF in 3T3-L1 CM.
      Although basic fibroblast growth factor (bFGF) and insulin-like growth factor I
      (IGF-I) were mitogenic for SP1 cells, neutralizing antibodies against IGF-I,
      bFGF, platelet-derived growth factor (PDGF), and epidermal growth factor (EGF)
      did not inhibit the mitogenic activity of 3T3-L1 CM. Immunoprecipitation and
      immunoblotting of HGF receptor/c-met showed that c-met is expressed at high level
      in SP1 cells, and is phosphorylated following HGF ligation. Together, our present
      data demonstrate that 3T3-L1 adipocytes secrete HGF, which stimulates SP1 cell
      growth by a paracrine mechanism. Furthermore, the mitogenic effect of 3T3-L1 CM
      requires HGF receptor ligation and activation of tyrosine kinase signaling
      cascades in SP1 cells. These results highlight the importance of stromal-tumor
      cell interactions and suggest that HGF secreted by adipocytes may be a key
      regulator of mammary tumor growth.

PMID- 7811386
TI  - Molecular cloning and expression of guinea pig cytochrome P450c17 cDNA (steroid
      17 alpha-hydroxylase/17,20 lyase): tissue distribution, regulation, and substrate
      specificity of the expressed enzyme.
AB  - In mammalian and fish species, P450c17 mediates both 17 alpha-hydroxylase and
      17,20-lyase activities in the synthesis of steroid hormones. Previous results
      have shown that among the adrenal steroid hydroxylase enzymes involved in adrenal
      C19 steroid and glucocorticoid synthesis, regulation of cytochrome P450c17 is of
      primary importance because it is localized at the key branch between
      glucocorticoid and C19 steroid synthesis. A cDNA library from guinea pig adrenal
      was constructed, and the complete 17 alpha-hydroxylase cytochrome P450 cDNA was
      isolated. The guinea pig P450c17 cDNA includes the full-length coding region
      (1,524 nucleotide), the complete 3' untranslated region (169 nucleotide), and 39
      bases of the 5' untranslated region. Our clone shares most of the features of the
      other P450c17 cDNAs; however, in addition, we identified a novel conserved region
      of 18 amino acids located in exon I between residues 80 and 97. This region
      presents the highest percentage of identity among the other P450c17 enzymes and
      is positioned one helixturn upstream of the important Ser106 on the corresponding
      human form. On Northern blot, the cDNA hybridizes with a major 1.8-kb mRNA and
      with two other related P450c17 mRNA of about 3 and 4 kb. P450c17 mRNA is equally
      distributed in male and female gonads and adrenals. Characterization of the
      enzymatic activity shows that 17 alpha-hydroxylase and 17,20-lyase are carried by
      a single protein, but in homogenates 17,20-lyase activity is barely detectable.
      Moreover, we demonstrate in vitro and in vivo that the guinea pig enzyme
      preferentially has very high levels of 17 alpha-hydroxylase and 17,20-lyase
      activities only toward delta 4 steroids. Second-messenger cyclic adenosine
      monophosphate and adrenocorticotropin specifically increased the abundance of
      P450c17 mRNA levels in guinea pig adrenal cells.

PMID- 7811387
TI  - cDNA cloning and efficient mitochondrial import of pre-mtHSP70 from rat liver.
AB  - Members of the 70-kD heat shock protein family have been found in all free-living
      organisms investigated and in major compartments of eukaryotic cells where they
      are essential to a wide range of functions, including protein folding and
      targeting. We have isolated a mitochondrial homolog (mtHSP70) from rat liver
      using ATP agarose affinity chromatography. Its identity was confirmed on the
      basis of immunological analysis and Ca(2+)-dependent autophosphorylation. Using
      protein sequence obtained from the amino termius and nine endo Lys-C peptide
      fragments, we have employed oligonucleotides to isolate a full-length cDNA clone.
      The open reading frame encodes a protein of 679 amino acids and calculated M(r)
      73,913 daltons. The sequence has a high degree of identity with other members of
      the HSP70 family, including Escherichia coli DnaK (51%), Saccharomyces cerevisiae
      SSC1p (65%), the constitutive cytosolic HSP70 from rat, HSC70 (46%), and the rat
      endoplasmic reticulum isoform, BiP, (49%). The cDNA encodes a precursor protein
      with a 46-amino-acid signal peptide that is absent from the protein isolated from
      rat liver. The protein also shows a high degree of identity (98%) with a protein
      isolated from mouse and human tissues (PBP74, Domanico et al., 1993; mortalin,
      Wadhwa et al., 1993a; CSA, Michikawa et al., 1993a); however, the intracellular
      localization of these proteins is uncertain. We show that the precursor of
      mtHSP70 is efficiently imported into isolated mitochondria from rat liver and
      processed from 74 kD to the mature 69-kD protein.

PMID- 7811388
TI  - Human neuropeptide Y1 receptor expressed in Escherichia coli retains its
      pharmacological properties.
AB  - The coding region of the gene for the human neuropeptide Y (NPY) Y1 receptor was
      fused to the maltose binding protein gene. Expression of this transcription unit,
      after derepression with isopropyl beta-D-thiogalactopyranoside, was evidenced by
      the appearance of a protein of higher molecular weight, as well as the native
      maltose binding protein, both of which were immunoreactive with anti-maltose
      binding protein antibodies. Specific [125I]NPY binding activity was found
      associated mainly with the inner bacterial membrane fraction, suggesting that the
      receptor is correctly folded in this membrane. Competition binding experiments
      using NPY Y1- and Y2-specific ligands clearly exhibited a NPY Y1 specific
      pharmacological profile with Kd values indistinguishable from those of the native
      receptor. These results suggest that the membrane environment required by the
      human NPY Y1 receptor for specific high-affinity ligand binding is conserved in
      this heterologous bacterial system and can be used for detailed analyses of
      ligand-receptor interaction and drug screening.

PMID- 7811389
TI  - Optimization of experimental variables influencing reporter gene expression in
      hepatoma cells following calcium phosphate transfection.
AB  - We describe a highly efficient calcium phosphate transfection protocol capable of
      achieving 100% transfection efficiency of reporter genes transiently expressed in
      the human hepatoma cell lines HuH7 and HepG2. This procedure, a modification of
      that described by Chen and Okayama, is reliable, reproducible, and eliminates the
      requirement for the inclusion of cotransfected internal control plasmids. While
      Chen and Okayama described the pH of the 2x BBS (N,N-bis[2-hydroxyethyl]-2
      aminoethanesulfonic acid-buffered saline) and DNA concentration as being critical
      factors for optimal transfection efficiency, we show that a reduced and strictly
      monitored standing time of the DNA/CaCl2/2x BBS cocktail prior to addition to
      cultured cells is essential for a particular combination of pH and DNA
      concentration. We also show that the inclusion of internal control plasmids can
      inhibit reporter gene activity in a promoter- and dose-dependent manner. The
      method so described is also applicable for the transfection of other mammalian
      cell lines including COS and HeLa, and conceivably for the generation of stable
      transfectants at high frequency.

PMID- 7811390
TI  - The significance of apolipoprotein E structure to the metabolism of plasma
      triglyceride-rich lipoproteins.
AB  - In this paper we analyse the structural organization of human apolipoprotein E
      (apoE) at the surface of triglyceride (TG)-rich lipoproteins, in relation to the
      metabolic pathway of these particles. ApoE acts as a receptor-binding ligand at
      the surface of chylomicrons and VLDL (very low density lipoproteins). The degree
      of exposure of apoE at the surface of lipoproteins and its affinity for the
      receptor both determine the uptake and catabolism of these lipoproteins. ApoE
      and/or apoB100, the major apolipoprotein constituent of LDL, contribute to the
      interaction of lipoproteins with five different cellular receptors: 1) the low
      density lipoprotein (LDL) receptor; 2) the LDL receptor-related protein (LRP); 3)
      the macrophage receptor for hypertriglyceridemic VLDL; 4) the scavenger receptor;
      5) the VLDL receptor. The degree of exposure of apoE at the surface of normo- and
      hyperlipidemic VLDL can modulate their uptake by the LDL receptor. Normolipidemic
      VLDL are poorly recognized by the LDL receptor whereas hypertriglyceridemic VLDL
      are cleared more efficiently through this pathway. On the other hand, the extent
      of apoE self-association, which is dependent upon the degree of hydrolysis of the
      TG-rich particles, can control their interaction with the LDL-receptor related
      protein. The lateral organization of apoE at the surface of TG-rich particles,
      its interaction with other apoproteins and its extent of self-association might
      therefore be important factors in the clearance of these lipoproteins. Finally,
      structural defects of apoE might result in an impaired interaction of apoE
      containing lipoproteins with these receptors and lead to the development of
      atherogenic dyslipidemias.

PMID- 7811391
TI  - Human protein NEFA, a novel DNA binding/EF-hand/leucine zipper protein. Molecular
      cloning and sequence analysis of the cDNA, isolation and characterization of the
      protein.
AB  - The cDNA libraries constructed from the human acute lymphoblastic leukemia cell
      line KM3 in the expression vector lambda gt11, were screened with the anti-CALLA
      (common acute lymphoblastic leukemia antigen) mAb (monoclonal antibody) J5. The
      selected J5-positive clone I containing a partial cDNA insert was isolated and
      sequenced. For completing the cDNA sequence the cDNA libraries were further
      screened by hybridization with the DIG (digoxigenin)-labelled DNA probe derived
      from clone I, the 5'-end region was analysed by 5'-RACE (rapid amplification of
      cDNA ends) using a sequence specific primer. In total a 1639 bp cDNA sequence was
      determined. The cDNA sequence contains a 1260 bp open reading frame and the
      untranslated 3'- and 5'-end sides. The 420 residue amino acid sequence, deduced
      from the cDNA sequence, unexpectedly differs fundamentally from CALLA (CD10)
      although clones I and II were J5-positive in immuno screening. The mature protein
      corresponding to the cDNA was isolated and characterized from the KM3 cells using
      polyclonal antisera raised against the in vitro expressed polypeptide from clone
      I. The protein is expressed on plasma membrane, in cytosol and is secreted into
      culture medium, its relative molecular mass was determined to be 55 kDa on SDS
      PAGE. The deduced amino acid sequence from cDNA was confirmed by peptide
      sequences. The new protein contains a basic amino acid rich putative DNA binding
      domain (b) with a potential nuclear targeting signal, two helix-loop-helix (HLH)
      motif regions, concurrently EF-hand motifs, an acidic amino acid rich region (a)
      between the EF-hands, and a leucine zipper (Z) motif. This DNA binding protein
      therefore is characterized by a linked motif "b/HLH/a/HLH/Z". The protein was
      designated NEFA: DNA binding/EF-hand/acidic amino acid rich region.

PMID- 7811393
TI  - Immunological identity of the two different molecular mass constitutive subunits
      of liver arginase.
AB  - A detailed understanding of the regulatory mechanisms of arginase in the cell
      will depend on the clarification of the origin of the two different molecular
      mass subunits and on the arrangements of them to constitute the native enzyme.
      Here, we show the immunological recognition of the 39.5 and 37.0 kDa subunits of
      arginase by antibodies against both subunits. We also find that the subunit
      stoichiometry (39.5 kDa: 37.0 kDa) present in purified arginase preparations as
      well as in fresh isolated microsomes and cytoplasm corresponds to 3:1, indicating
      high prevalence of a constant arrangement of the constitutive subunits of
      arginase. These findings represent evidence for a limited posttranscriptional or
      posttranslational modification of only a fraction of the synthesized arginase in
      liver.

PMID- 7811392
TI  - Specific inhibition of cyclic AMP-dependent protein kinase by the antimalarial
      halofantrine and by related phenanthrenes.
AB  - The phenanthrenemethanol antimalarial halofantrine is a potent inhibitor of
      bovine heart and rat liver cyclic AMP-dependent protein kinase catalytic subunit
      (cAK) (IC50 values 2.1 microM and 0.6 microM, respectively). The inhibition of
      rat liver cAK by halofantrine is non-competitive with respect to both ATP and to
      the synthetic peptide substrate employed (LRRASLG). Halofantrine is a poor
      inhibitor of calmodulin-dependent myosin light chain kinase (MLCK) and wheat
      embryo Ca(2+)-dependent protein kinase (CDPK) and does not inhibit rat brain
      Ca(2+)- and phospholipid-dependent protein kinase C (PKC). In contrast, the
      acridine-based antimalarial quinacrine and a variety of quinoline-based
      antimalarials are very poor inhibitors of cAK, the best inhibitor being
      chloroquine (IC50 for bovine heart cAK, 80 microM). Quinacrine and the quinoline
      based antimalarials variously inhibit CDPK, PKC and MLCK albeit at relatively
      high concentrations (about 1 to 4 x 10(-4) M), the best inhibitors found being
      primaquine, pentaquine and mefloquine (IC50 values for MLCK 49, 103 and 33
      microM, respectively). A number of phenanthrene derivatives having a 9-hydroxy or
      9-keto substituent, namely phenanthrenequinone, 6(5H)-phenanthridinone and 9
      phenanthrol are potent inhibitors of bovine heart cAK (IC50 values 8, 10 and 10
      microM, respectively) and of MLCK (IC50 values 6, 53 and 10 microM,
      respectively). The selective, high affinity interaction of halofantrine with cAK
      may contribute to biological effects in vivo of this clinically-employed
      antimalarial compound.

PMID- 7811394
TI  - Non-Michaelis-Menten kinetics of zero-trans glucose uptake by trophoblast cells
      from human term placentae and by choriocarcinoma (JEG-3/JAR) cells.
AB  - Maternal glucose is a major substrate for placental and fetal metabolism. The
      kinetics of its uptake into placental trophoblast cells has not been
      characterised yet and was therefore investigated in the present study. In
      addition to trophoblast cells isolated from human term placentae, JEG-3 and JAR
      choriocarcinoma cells were used. Measurements were carried out in 5 s intervals
      until 30 s with the non-metabolisable glucose analogue 3-O-[14C]methyl-D-glucose
      using confluent cells adhering to glass coverslips. L-[1-14C]glucose was used to
      correct for extracellular trapped tracer and diffusion. The uptake was rapid and
      saturable. It reached equilibrium after 30 s at 20 degrees C and could be
      inhibited by 0.4 mmol/l cytochalasin B up to 98%. The choriocarcinoma cells took
      up twice as much glucose as trophoblast cells. Fitting the experimental data to
      the Michaelis-Menten equation by non-linear regression failed to adequately
      describe the data, even when a contribution of diffusion to total uptake was
      considered. Introducing the Hill coefficient n into the Michaelis-Menten equation
      significantly improved the quality of the fits as was assessed by three
      statistical criteria. Using this equation modified for allosteric kinetics (v =
      k[To] [S]n)/(Km + [S]n)), parameters were calculated as Km = 12 mmol/l, Vmax = 17
      fmol/l s-1 per cell, n = 1.1 for trophoblast cells; Km = 13 mmol/l, Vmax = 27
      fmol/l s-1 per cell, n = 1.2 for JEG-3 cells and Km = 29 mmol/l, Vmax = fmol/l s
      1 per cell, n = 1.4 for JAR cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7811395
TI  - The mannose transporter of Escherichia coli K12: oligomeric structure, and
      function of two conserved cysteines.
AB  - The mannose transporter of E. coli is a member of the phosphotransferase system.
      It consists of two membrane spanning subunits, IICMan (27.64 kDa) and IIDMan
      (31.02 kDa) and a peripheral subunit IIABMan (35.02 kDa). It acts by a mechanism
      that couples vectorial translocation to phosphorylation of the substrate. The
      subunit ratio determined from densitometric scans of polyacrylamide gels is close
      to IIABMan2 IICMan1 IIDMan2. A molecular mass of 100 +/- 20 kDa was calculated
      from electronmicrographs of freeze fractured proteoliposomes containing particles
      of the IICMan/IIDMan subcomplex with a mean diameter of 6.3 +/- 1.1 nm. This is
      most compatible with IICMan:IIDMan subunit compositions of 1:2 (89.7 kDa). Fusion
      proteins between IICMan and IIDMan were generated, with the subunits connected
      either by a two-residue linker or a 20 residue Ala Pro rich hinge. The fusion
      proteins had 5%-15% of control phosphotransferase activity. The one with the Ala
      Pro rich linker could be cleaved with trypsin resulting in a 7 fold increase of
      activity while the fusion with the two residue linker was resistant to limited
      trypsinolysis. Taking into account the inside-out orientation of the membrane
      vesicles the C-terminus of IICMan and the N-terminus of IIDMan are both predicted
      to be on the cytoplasmic side of the membrane. Two cysteines in IICMan and IIDMan
      which are conserved in the homologous subunits of the fructose transporter of
      Bacillus subtilis and of sorbose transporter of Klebsiella pneumoniae are not
      necessary for phosphotransferase function.

PMID- 7811396
TI  - Amino acid sequence of the alpha A- and beta-polypeptide chains of the Ryukyu
      rufous turtle dove (Streptopelia orientalis Stimpsoni) hemoglobin.
AB  - Only one hemoglobin component is recognized in the erythrocytes of the adult
      Ryukyu rufous turtle dove. We have determined the amino acid sequence of the
      alpha A-globin and the beta-globin by conventional protein sequence analysis. The
      sequences of both the alpha A- and the beta-globins were highly similar to
      domestic pigeon hemoglobin. The alpha A-globin has 6 exchanges and beta-globin
      has 4 exchanges compared with the corresponding domestic pigeon chains.

PMID- 7811397
TI  - New concepts in botulinum toxin therapy.

PMID- 7811398
TI  - A review of the use of chemoprotectants in cancer chemotherapy.
AB  - Dose-limiting toxicity secondary to antineoplastic chemotherapy is principally
      due to the inability of the drugs to differentiate between normal and malignant
      cells. This results in normal tissue damage, as well as the desired antitumour
      effect. Toxicity may be acute, as in cisplatin-induced nephrotoxicity or
      alkylating agent myelotoxicity and haemorrhagic cystitis, or cumulative, as in
      anthracycline-related cardiac toxicity or cisplatin neurotoxicity. The
      consequences of this often include serious adverse effects and the inability to
      deliver adequate dose-intensive therapy against the cancer. Chemoprotective
      agents have been developed to provide site-specific protection against normal
      tissue toxicity, without compromising antitumour activity. Several
      chemoprotective compounds have recently been developed, including dexrazoxane
      (ICRF-187), amifostine (ethiofos: WR-2721), mesna and ORG-2766. Initial results
      confirm their promise as selective protective agents, although further randomised
      trials are required to identify their optimal role when used alone or in
      combination with other toxicity modifiers, including haematopoietic growth
      factors, with the ultimate aim being adequate dose escalation of chemotherapy to
      overcome tumour resistance.

PMID- 7811399
TI  - The risks and benefits of corticosteroids in advanced cancer.
AB  - Corticosteroids are extensively prescribed in advanced cancer for various
      specific indications (e.g. spinal cord compression), for pain relief, as hormone
      therapy and to stimulate appetite and wellbeing. Choice of corticosteroid is
      dictated largely by local fashion, and times of administration are more
      traditional than pharmacological. Corticosteroids have many potential
      disadvantages, some life-threatening (e.g. masked septicaemia). Others are
      seriously debilitating (e.g. myopathy, avascular bone necrosis). Oropharyngeal
      candidiasis is a common complication. Corticosteroids are withdrawn in about 5%
      of patients because of unacceptable adverse effects, including moon-face and
      diabetes mellitus. Corticosteroid hypersensitivity occurs, and the succinate
      salts have been associated with bronchospasm. Steroid pseudorheumatism may occur
      with high dose therapy or when tailing off after a prolonged course. Important
      drug interactions with corticosteroids relate to salt and water retention, and
      decreased glucose tolerance. Some anticonvulsants cause an increased clearance of
      corticosteroids and, with dexamethasone, up to a 50% reduction in the anticipated
      effect. The benefit of corticosteroids in terms of increased appetite, mood and
      activity has been demonstrated in several controlled trials. The effect may well
      be time-limited in most patients. In several studies, corticosteroids have
      resulted in an analgesic-sparing effect. Some centres use very high doses of
      dexamethasone in cases of spinal cord compression, although the justification for
      these is not obvious. Corticosteroids are used to help relieve nerve compression
      pain and in symptomatic raised intracranial pressure. Corticosteroids are also
      injected locally into or around bone metastases, particularly ribs and the sacro
      iliac joints. Epidural injections are used for patients with troublesome
      intractable low back pain. Corticosteroids are now used less often in
      hypercalcaemia because of poor response rates. More benefit is obtained, however,
      if high dosages are used, e.g. prednisolone 60 to 80 mg/day. Dexamethasone is
      widely used as an antiemetic in association with chemotherapy. Some centres use
      dexamethasone by continuous subcutaneous infusion in selected patients when the
      oral route is not feasible. The choice of starting dose of a corticosteroid is
      largely arbitrary. It is important, however, not to miss a possible treatment
      benefit by prescribing too low a dose. For most patients, an initial dosage of
      prednisolone of 30 to 60 mg/day (dexamethasone 4 to 8 mg/day) is appropriate. In
      patients with anorexia, there are several alternative options that should be
      considered. There is evidence to suggest that patients with advanced cancer
      receiving a corticosteroid are not as closely monitored as other patients. There
      is a need to state clearly in writing the reason(s) for prescription and to
      review after 1 or 2 weeks.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7811402
TI  - Adverse interaction between warfarin and indomethacin.

PMID- 7811400
TI  - Management of osteoporosis and Paget's disease. An appraisal of the risks and
      benefits of drug treatment.
AB  - Osteoporosis is a major public health problem occurring primarily among the
      postmenopausal population. Osteoporosis is a preventable disease, but despite
      several advances in its prevention, treatment of the established disease to date
      remains a major challenge to be managed by primary care physicians. Stabilisation
      of bone mass and prevention of falls are of paramount importance in any
      therapeutic programme for osteoporotic patients with established vertebral
      fractures. Drug therapy for osteoporosis can be divided operationally into 2 main
      categories: those that inhibit bone resorption, and thus reduce bone turnover,
      and those that stimulate bone formation, exerting an anabolic effect. Therapeutic
      agents that inhibit bone remodeling would appear to be best suited to those
      patients with high turnover osteoporosis (about 30%). Included in this category
      are calcium, vitamin D and its metabolites, gonadal steroids, calcitonin,
      ipriflavone and bisphosphonates. Although estrogen replacement therapy has been
      proven to be effective in older females, calcitonin appears to be the treatment
      of choice for this population since it stabilises or increases bone mass and also
      has reported analgesic properties. Drugs that stimulate bone remodeling or bone
      formation would be best suited to patients with low turnover osteoporosis (about
      70%). The agent in this class that is widely used is sodium fluoride. New
      therapies include intermittent injections of synthetic parathyroid hormone, and
      cyclic bisphosphonates to activate then depress resorption and formation. Any
      attempts to stabilise the skeleton with any drug regimen must be accompanied by
      an adequate calcium supply, i.e. 1200 to 1500 mg/day). The theoretical basis of
      tailoring treatment for osteoporosis to the underlying histology has not yet been
      fully proven, but there is increasing experimental support to this approach.
      Drugs that inhibit bone turnover, such as calcitonin, appear to be effective in
      increasing bone mass for 1.5 to 2 years, about the time it would take to
      replenish the remodeling space in a patient with high turnover osteoporosis. In
      contrast, although bone mass appears to increase for as long as 5 years in
      patients treated with sodium fluoride, there has been no consistent reduction in
      occurrence of vertebral or hip fractures. Paget' disease of bone is a focal
      disorder of the skeleton characterised by excessive resorption and subsequently
      disorganised formation of bone. The aetiology of the disease is unknown. Paget's
      disease may be mono-ostotic or polyostotic; pain and bone deformities due to
      enlargement of skeletal segments represent the main clinical aspects. However, in
      many patients the disease may be asymptomatic.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7811403
TI  - Hormone replacement in the hypopituitary patient.

PMID- 7811401
TI  - Mechanisms of unpredictable adverse drug reactions.
AB  - Adverse drug reactions are common problems associated with therapy, and are major
      sources of morbidity and mortality. There are numerous types of drug reactions,
      including predictable drug reactions such as side effects, toxicity, drug
      interactions and secondary effects that can be anticipated when planning therapy.
      There are also a number of unpredicted adverse effects, which are unexpected
      consequences of therapy. The least severe unpredicted adverse drug reaction is
      intolerance, which appears to be an exaggeration of pharmacological or toxic
      effects of the drug among vulnerable subsets of patients. Some of the most severe
      and life-threatening adverse drug reactions are allergic. These adverse effects
      can be mediated by a number of mechanisms, including the development of drug
      specific IgE, serum-sickness-like reactions in response to drug-antibody
      complexes, direct release of inflammatory mediators, or involvement of the immune
      system by mechanisms that are poorly understood. Idiosyncratic adverse drug
      reactions are a heterogeneous group of adverse effects that are not predictable
      from the pharmacological actions of the drug. Many of these reactions occur as a
      consequence of pharmacogenetic variations in drug bioactivation and drug or
      metabolite detoxification or clearance. The physician must be vigilant for the
      possibility of unpredictable adverse drug reactions during or after therapy.
      Research currently underway may afford the opportunity to predict, and hopefully
      prevent, some of these adverse reactions in the future.

PMID- 7811404
TI  - Imaging after titanium cranioplasty.
AB  - Titanium cranioplasty has been used in our unit for reconstruction of cranial
      defects following trauma, tumour resection and bone loss due to postcraniotomy
      infection. It has previously been assumed that imaging to assess recurrence of
      disease progression after cranioplasty would be severely compromised in the
      presence of metallic material. Titanium is a non-ferrous metal of low atomic
      number, which is relatively radiolucent and allows exceptionally clear images to
      be obtained without significant degradation of image quality, on CT and magnetic
      resonance (MR) imaging. Cases are presented that demonstrate the use of CT
      contrast cisternography and MR imaging after titanium cranioplasty. On the basis
      of its strength, biocompatibility and excellent handling characteristics, allied
      to its suitability for all post-operative imaging techniques, we conclude that
      titanium plate is the material of choice for cranioplasty.

PMID- 7811405
TI  - A modified frontal approach for anterior circle of Willis aneurysms.
AB  - A new approach to anterior circulation aneurysms is described in which the
      position of the surgeon is radically different from usual, allowing an enhanced
      view along the plane of the parent artery with minimal retraction and proximal
      control. The position of the surgeon and assistant are comfortable, and the scrub
      nurse's access to the surgeon's hands is greatly enhanced.

PMID- 7811406
TI  - The presence of tumour necrosis factor in CSF and plasma after severe head
      injury.
AB  - In a cohort of victims of traumatic brain injury, 18 out of 50 patients had a
      plasma tumour necrosis factor (TNF) concentration above 2 pg/ml within 24 h of
      injury (mean 12.19, SD 45.96 pg/ml). Twenty-six had CSF samples available of
      which 17 demonstrated TNF concentrations above 1 pg/ml (mean 3.98, SD 3.61
      pg/ml). We conclude that traumatized brain parenchyma is a significant source of
      TNF activity and implicate the cytokine in cellular metabolic derangements
      following head injury.

PMID- 7811407
TI  - Primary lymphoma of the central nervous system.
AB  - Eleven patients with primary lymphoma of the central nervous system were seen in
      the King Faisal Specialist Hospital and Research Centre, Saudi Arabia, between
      1986 and 1992. None had previously received immunosuppressive therapy. All cases
      were confirmed by biopsy and histopathological studies. Of the eleven patients,
      six had debulking of the tumour, seven received radiation therapy and six
      received chemotherapy. This report confirms the very poor prognosis for patients
      with primary lymphoma of the central nervous system, with only a few long-term
      survivors.

PMID- 7811408
TI  - MRI cisternography, and the localization of CSF fistulae.
AB  - Accurate localization of CSF fistulae not only makes the planning of surgery
      easier, but it also increases the chances of successful dural repair and
      eliminates negative exploration. CSF fistulae localization has been a problem for
      many years, and several methods have been used to pin-point the site of CSF
      leakage with variable degree of success. Recently, contrast CT cisternography
      (CCTC) has replaced radio-isotope cisternography (RIC) in many centres. However,
      both methods are invasive, time consuming, contraindicated in patients with
      intracranial mass lesions and insensitive in detecting inactive CSF leaks.
      Furthermore, in both, ionizing radiation is used and both techniques may lead to
      allergic reactions or seizures. On the other hand, T2-weighted Magnetic Resonance
      Imaging (MRI) shows the CSF as a high signal without the need to inject contrast
      media intrathecally. Furthermore, MRI demonstrates the intracranial anatomy and
      pathology in detail in multiple planes within a relatively short time. MRI does
      not involve ionizing radiation and therefore is safely repeatable. MRI using T2
      weighted sequences should be an ideal tool to locate precisely the site of CSF
      fistulae. This paper describes our experience with MRI cisternography in CSF
      fistulae localization. Eleven patients with inactive CSF fistulae were
      investigated. MRI cisternography localized the site of fistula in each case. All
      patients were explored surgically and the site of CSF fistula was confirmed and
      repaired intradurally with a pericranial graft and fibrin glue without recurrence
      or meningitis.

PMID- 7811409
TI  - Acute subdural haematoma secondary to ruptured intracranial aneurysm: diagnosis
      and management.
AB  - Acute subdural haematoma secondary to a ruptured intracranial aneurysm may lead
      to coma or sudden death. We describe five cases encountered in our department
      over the last 3 years emphasizing the differential diagnosis and approaches to
      management.

PMID- 7811410
TI  - The management of cerebellar abscess since the introduction of CT scanning.
AB  - Sixteen patients with surgical infection of the posterior fossa are presented.
      There were 14 patients with cerebellar abscess, one patient with a solitary
      posterior fossa subdural empyema, and another with a combined cerebellar abscess
      and subdural empyema. Two of the cerebellar abscess patients also had
      supratentorial infections. The presenting features, aetiology, radiology and
      bacteriology are discussed with particular reference to differences in abscess re
      accumulation, and outcome between those managed by aspiration and excision. We
      have been unable to show that either method of treatment is superior to the
      other. An overall mortality rate of 19% was achieved; however, for those with
      parenchymal cerebellar abscesses this was reduced to 13%. We conclude that burr
      hole aspiration with regular CT is a satisfactory method of treatment for
      cerebellar abscess.

PMID- 7811411
TI  - Spontaneous cerebral haemorrhage from cerebral amyloid angiopathy.
AB  - Three cases of spontaneous intracerebral haemorrhage treated by acute evacuation
      of haematoma are described. All cases proved to have cerebral amyloid angiopathy
      as the primary cause of the haemorrhage. Only one patient survived. Previous
      reports are discussed.

PMID- 7811412
TI  - Validation of CT targeting for functional stereotaxis with postoperative magnetic
      resonance imaging.
AB  - Using postoperative magnetic resonance imaging the accuracy of CT-guided three
      dimensional targeting of stereotactic thalamotomy for movement disorders was
      demonstrated in 13 patients. CT guidance should be adopted for functional
      neurosurgery in preference to ventriculographic guidance as it can be shown to be
      sufficiently accurate and it is far less disturbing to the patient.

PMID- 7811413
TI  - A new retractor for the anterior cervical approach.

PMID- 7811414
TI  - Optochiasmal arachnoiditis induced by muslin wrapping of intracranial aneurysms.
      A report of two cases and a review of the literature.
AB  - Muslin wrapping of intracranial aneurysms has been used for many years, but
      muslin-induced optochiasmal arachnoiditis was first reported only in 1978, as a
      complication with catastrophic loss of vision. In this study of 54 cases wrapped
      with muslin over the last six years, two cases of optochiasmal arachnoiditis
      occurred. Three patients had early rebleeding among the 27 who had wrapping as
      the only treatment of the aneurysm.

PMID- 7811415
TI  - Multiple cerebral aneurysms, multiple meningiomas and multiple subcutaneous
      angiolipomas: a case report.
AB  - The simultaneous occurrence of multiple meningiomas, multiple distally located
      cerebral aneurysms and numerous subcutaneous lipomata in a 48-year-old man is
      reported. There was no evidence of neurofibromatosis, connective tissue disease
      or abnormality of collagen synthesis. We propose a possible genetic link between
      these three disparate conditions in our patient.

PMID- 7811416
TI  - Massive benign osteoblastoma of the clivus and atlas.
AB  - A case of massive benign osteoblastoma involving the clivus and atlas is
      reported. Usually, these tumours involve the posterior elements of a vertebra and
      are detected when small as a result of the usual presenting symptom of pain. The
      unusual site, massive size and presentation with neurological deficits are rare
      for benign osteoblastomas. The problems encountered in the surgical management of
      the patient are discussed.

PMID- 7811417
TI  - Twenty-year survival following excision of primary CNS lymphoma without radiation
      therapy: case report.
AB  - The prognosis of primary central nervous system lymphoma (PCL) is very poor with
      a mean survival of 3-6 months without treatment and 15-45 months following
      radiation therapy. PCL is very sensitive to radiation therapy, but recurrence is
      frequent. A response of the tumour to steroids has also been documented. This
      report describes a patient who had surgery for a solitary PCL without subsequent
      radiation therapy or steroid medication and who had no evidence of tumour
      recurrence 16 years later. He remains well 20 years after surgery. No case of
      long-term survival following surgery alone for PCL has been reported previously.
      Surgical excision may have a place in the management of solitary PCL.

PMID- 7811418
TI  - Ossification of the posterior longitudinal ligament mimicking cord compression
      from a dorsal disc protrusion: a cautionary tale.
AB  - A patient with focal anterior compression of the dorsal cord at the level of the
      D6/7 disc was mistakenly diagnosed as a dorsal disc protrusion on the basis of CT
      myelography. The CT scanning had been confined to axial views at the level of the
      cord compression. A transthoracic exploration failed to reveal a disc protrusion
      and the correct diagnosis, ossification of the posterior longitudinal ligament,
      was only revealed by a subsequent sagittal CT scan. This case emphasizes the
      dangers of relying on limited axial imaging in diagnosing a spinal lesion.

PMID- 7811419
TI  - Peripheral neuroepithelioma presenting as a spinal cord tumour.
AB  - A case of spinal cord tumour in a 41-year-old man is presented. The initial
      diagnosis was of metastatic small cell tumour. One year postoperatively he
      presented with a left cerebellopontine angle tumour which resolved with
      radiotherapy. Three years after initial presentation he remains well with no
      evidence of a primary tumour. Histological review shows the tumour to be a
      peripheral neuroepithelioma, which has not previously been reported to affect the
      spinal cord. The differential diagnosis of small cell spine tumours is discussed.

PMID- 7811420
TI  - Multiple nocardial brain abscesses: report of two patients.
AB  - Two patients presented with nocardial brain abscesses, one as secondary to
      overwhelming pulmonary infection following a thoracic empyema, the second as a
      primary abscess. Both patients had immunopression. Such an infection should be
      considered early in any patient who is immunocompromised.

PMID- 7811421
TI  - Consequences of prolonged inhalation of ozone on F344/N rats: collaborative
      studies. Part III: Effects on complex carbohydrates of lung connective tissue.
AB  - Glycosaminoglycans are constituents of proteoglycans, which are integral
      components of lung connective tissue. Glycosaminoglycans not only provide
      structural support to organs, but also influence extracellular matrix assembly,
      cell adhesion, and cell proliferation. Changes in the metabolism of
      glycosaminoglycans have been noted in several pulmonary diseases, for example,
      pulmonary fibrosis and emphysema. We studied quantitative and qualitative changes
      of glycosaminoglycans in the lungs of rats exposed to a range of ozone levels (0,
      0.12, 0.5, 1.0 parts per million) for 20 months. Glycosaminoglycans were isolated
      from dry-defatted lung tissues through successive digestions by pronase, papain,
      and 2 M sodium hydroxide. The glycosaminoglycans then were fractionated into
      individual components using high-performance liquid chromatography. The
      concentration of total glycosaminoglycans in the tissues varied from 1.5 to 4.2
      micrograms of uronate/mg of dry-defatted tissue. Although wide variations in
      total glycosaminoglycan concentrations exist among individual animals within each
      exposure group, regression analyses of data indicate a monotonic and
      statistically significant decrease of total glycosaminoglycans after ozone
      exposure (p = 0.02). Among individual glycosaminoglycans, hyaluronan, chondroitin
      4-sulfate, and chondroitin 6-sulfate levels decreased significantly (p < 0.001, p
      < 0.05, and p < 0.01, respectively) in animals exposed to ozone when compared
      with control animals. Heparan sulfate concentration exhibited a significant (p <
      0.05) trend toward increase with increasing doses of ozone, but the difference in
      heparan sulfate concentration between ozone-exposed animals and control animals
      was not significant. Gel filtration studies of glycosaminoglycans in pooled
      samples indicated that the molecular size of hyaluronan in animals exposed to
      ozone was lower than it was in control animals. We noted differences in heparan
      sulfate's chemical properties and affinity to antithrombin III in ozone-exposed
      animals and control animals. Although these studies do not provide the mechanism
      responsible for the observed changes in the lung glycosaminoglycans in ozone
      exposed animals, the observations indicate that inhalation of ozone for 20 months
      affects normal cellular metabolism of proteoglycans, which may contribute to the
      functional impairment of the lung.

PMID- 7811422
TI  - Neurofibromatosis type 1.
AB  - The authors review the present data on the clinical and molecular aspects of
      neurofibromatosis type 1 (NF1). In the clinical part attention is given to the
      frequent observation of learning disabilities in NF1 children. In these children
      visual-spatial integration deficits and an increased incidence of school
      performance problems are observed. The NF1 gene is located on chromosome 17
      (17q11.2), and is highly conserved across species. Up to now only a limited
      number of mutations in this gene have been characterized, and this shows a
      general lack of genotype-phenotype correlation. Evidence is given that the NF1
      gene acts as a true tumor suppressor gene and that oncogenesis in NF1 is a
      complex multistep phenomenon with the second hit in the NF1 gene as the
      initiating event. The importance of specialized multidisciplinary outpatient
      clinics for neurofibromatosis is emphasized because of the complexity of follow
      up and treatment of these patients.

PMID- 7811423
TI  - Genetic counseling in limb reduction defects.
AB  - During several years experience in a multidisciplinary out-patient clinic for
      children with congenital hand malformations a systematic approach was devised to
      arrive at an accurate diagnosis and recurrence risk in patients with congenital
      limb reduction defects. Classification and diagnostic work-up was done according
      to a protocol, derived from data in the literature and from our own experience.
      This protocol is described for the different types of congenital upper limb
      reduction defects.

PMID- 7811424
TI  - Ileal hypoplasia in the infant of a diabetic mother.

PMID- 7811425
TI  - Congenital marked hypertrichosis and Laband syndrome in a child: overlap between
      the gingival fibromatosis-hypertrichosis and Laband syndromes.
AB  - Gingival fibromatosis may be reported as an isolated finding or associated with a
      number of distinct and frequently inherited group of disorders. The
      characteristics of the Laband syndrome include gingival hyperplasia, dysplasia of
      the terminal phalanges and nails of extremities, hepatosplenomegaly and facial
      dysmorphism. Another well-known syndrome with gingival fibromatosis associates
      generalized hypertrichosis and inconstant mental retardation and epilepsy. We
      report a case with features of Laband syndrome and congenital marked
      hypertrichosis, suggesting overlap between these two genetic disorders.

PMID- 7811426
TI  - Hyperbrachycephaly, short face, midface hypoplasia, fusion of cervical vertebrae,
      radiolucent bone defects, and severe destruction of periodontium--a new syndrome:
      craniofaciocervical osteoglyphic dysplasia.
AB  - A patient with an unusual combination of findings, which do not fit in any of the
      known syndromes, is presented. The patient, a 24.5-year-old male of normal growth
      and intelligence, manifests craniofacial dysmorphism, radiolucencies in the skull
      and in the cervical vertebrae, progressive alveolar bone loss and fusion of
      cervical vertebrae. The young man does not exhibit any other systemic,
      hematological, biochemical, chromosomal or immunological abnormality, except for
      IgA deficiency.

PMID- 7811427
TI  - Genetic nosology and counseling of humeroradial synostosis.
AB  - From published cases of humeroradial synostoses three entities can be delineated:
      AD ankylosis of the elbow as a part of a systemic disorder causing multiple
      synostoses (symphalangism), AR humeroradial synostosis with dysgenesis of the
      ulna (and fibula?) but without oligodactyly as part of a syndromal disorder, non
      germinal uni- or bilateral humeroradial synostosis as part of ulnar malformation
      and oligodactyly. Three new observations are considered examples of the latter
      entity.

PMID- 7811428
TI  - The McKusick-Kaufman syndrome: phenotypic variation observed in familial cases as
      a clue for the evaluation of sporadic cases.
AB  - The characteristic clinical picture of the McKusick-Kaufman syndrome was observed
      in a girl of Belorussian background. A supernumerary nipple was the only finding
      not previously described in reported familial cases of this syndrome. In general,
      the range of phenotypic variability should be the same in both familial and
      sporadic cases. For this reason we feel that some sporadic cases reported as
      patients with unusual variants of the McKusick-Kaufman syndrome have more likely
      "new" genetic syndromes or non-genetic conditions, which only resemble the
      syndrome. The comparison of the phenotypes of alleged sporadic cases with
      familial cases of single gene syndromes should be helpful in syndrome
      delineation, if the number of familial observations is sufficient.

PMID- 7811429
TI  - Hypertelorism-microtia-clefting (HMC) syndrome.
AB  - We present here a new patient with the HMC syndrome, born from consanguineous
      parents. This observation confirms the existence of the HMC syndrome as a rare
      autosomal recessive disease, of which only five previous instances have been
      published previously. The occurrence of facial clefts in relatives may represent
      partial expression in the heterozygotes, and may indicate that HMC syndrome is
      the homozygous state for one of the clefting genes.

PMID- 7811430
TI  - A case of term mors in utero in a chromosome 11p linked long QT syndrome family.
AB  - Isolated congenital long QT syndrome is an autosomal dominant disorder
      characterized by recurrent syncopes, ventricular arrhythmias, or sudden death
      often accompanied by a prolonged QTc interval on ECG. On the occasion of a
      pregnancy complicated by an intra-uterine death of a full term baby with
      prolonged bradycardia a long QT syndrome was diagnosed in the mother. Familial
      examination revealed a prolonged QTc in her mother, brother and sister, all with
      positive history of syncopes. DNA linkage analysis was subsequently performed in
      this family with DNA markers on the short arm of chromosome 11. Four of the
      children in the family, younger than 5 years, were found to be asymptomatic
      carriers. Three of them showed a clear QTc prolongation on a 12 lead ECG. Another
      showed QTc prolongation during Holter monitoring but had a normal basic ECG.
      Measurement of QTc interval in families affected by the long QT syndrome is
      helpful but does not always permit an accurate diagnosis. Familial screening with
      DNA linkage analysis especially in families where a member is affected by the
      syndrome, can reveal "masked" cases which can further be investigated with Holter
      or effort ECG. The identification of locus heterogeneity of the long QT syndrome
      complicates genetic diagnosis. Only prospective studies in more families with
      long QT syndrome can show the additional diagnostic and prognostic value of DNA
      linkage.

PMID- 7811431
TI  - Apert syndrome, an antenatal ultrasound detected case.
AB  - Apert's syndrome or acrocephalosyndactyly type I is an autosomal dominant
      craniosynostosis syndrome with abnormalities of the hands and feet. Most cases
      occur as new mutations. Mental retardation is frequent because of central nervous
      system abnormalities. A case of Apert's syndrome detected by antenatal ultrasound
      examination is reported by the authors.

PMID- 7811432
TI  - Neurocristopathy in mother (ganglioneuroblastoma) and daughter (aganglionosis):
      incidental or causal?
AB  - We report on a mother who had been treated for a ganglioneuroblastoma and her
      daughter who had a long segment aganglionosis. Review of the relevant literature
      and recent molecular findings warrant the conclusion that most likely, there is a
      causal relation between these two neurocristopathies.

PMID- 7811434
TI  - Normal/trisomy 13 mosaicism in a 38-year-old male.
AB  - A 38 year-old male patient with normal/trisomy 13 mosaicism is reported. The
      phenotype-karyotype characteristics are reviewed and discussed.

PMID- 7811433
TI  - A patient with pituitary growth hormone deficiency and May-Hegglin anomaly: a
      distinct entity?
AB  - Pituitary growth hormone deficiency, associated with the May-Hegglin anomaly in
      peripheral blood (hereditary thrombocytopenia in association with giant platelets
      and inclusion bodies in the leukocytes) was found in a female patient. Both
      abnormalities are known to exist separately in human and to be transmitted in an
      autosomal dominant fashion. Whether this patient presented coincidentally with
      the two conditions or the two abnormal features have a single cause, cannot be
      resolved by the observation presented.

PMID- 7811435
TI  - Anti-inflammatory drugs: 1-(2-hydroxyethyl)pyrrolidinium salt of diclofenac.
AB  - In the solid-state structure of N-(2-hydroxyethyl)pyrrolidinium (2-[(2,6
      dichlorophenyl)amino]phenyl)acetate, C6H14NO+. C14H10Cl2NO2-, the asymmetric unit
      contains two independent ion pairs differing mainly in the conformation of the
      cation. A complex network of inter- and intramolecular hydrogen bonds is present.

PMID- 7811436
TI  - Nonmodulating trait may precede the development of hypertension.
AB  - The nonmodulating trait thought to explain development of hypertension in 25 to
      35% of patients, is characterized by abnormal angiotensin II (AII)-mediated
      control of aldosterone release and renal blood flow (RBF). Some data support the
      possibility that nonmodulation is an inherited trait, but others argue that it is
      an acquired epiphenomenon of the hypertensive state. We report the first case of
      a normotensive patient with nonmodulation who subsequently developed frank
      hypertension. Patient RR was studied on six occasions over a 5-year period, two
      while normotensive, four while hypertensive. This patient consistently
      demonstrated an abnormally low plasma aldosterone response to AII (3 ng/kg/min)
      on a low salt (10 mEq sodium) diet while both normotensive and hypertensive. A
      consistently abnormally depressed RBF response to AII on a high salt (150 to 200
      mEq sodium) diet as well as a depressed RBF increment when the diet was changed
      from low salt to high salt were also noted. Thus, RR demonstrated nonmodulation
      by multiple criteria while both normotensive and hypertensive. We conclude that
      the nonmodulating trait may be a heritable defect that leads to the development
      of hypertension and is not an epiphenomenon.

PMID- 7811437
TI  - Microalbuminuria in young adults related to blood pressure in a biracial (black
      white) population. The Bogalusa Heart Study.
AB  - The association between microalbuminuria and blood pressure levels was examined
      in young white and black adults (n = 1131) aged 19 to 32 years. Urinary ratio of
      albumin (mg/L) to creatinine (mmol/L) was used as an estimation of urinary
      albumin excretion. Black men and women compared with their white counterparts had
      higher levels of blood pressure. Significantly positive correlations between
      urinary albumin excretion and systolic and diastolic blood pressures were
      observed in black men (r = 0.20 and r = 0.24, P < .01) and black women (r = 0.15
      and r = 0.14, P < .05). Similar correlations of significance were not seen in the
      white counterparts. Systolic and diastolic blood pressure levels were
      significantly higher in normotensive black subjects (< 140/90 mm Hg) with
      increased urinary albumin excretion (> or = 90th percentile) than in those
      without increased urinary albumin excretion. After accounting for potential
      confounding by age, sex, and body mass index, blacks in the uppermost systolic
      and diastolic blood pressure group were 7.1 times (95% CI, 2.0 to 25.8) and 4.8
      times (1.3 to 18.3), respectively, as likely to have elevated albumin/creatinine
      excretion as those in the lowest group. In contrast, the likelihood for elevated
      albumin/creatinine excretion were 0.9 times (95% CI, 0.5 to 2.2) and 1.1 times
      (0.5 to 2.3), respectively, in whites, which were not significant. These data
      suggest that a stronger association between blood pressure levels and urinary
      albumin excretion exists in young blacks than in whites, which supports the
      notion that blacks may be more susceptible to renal damage from relatively low
      levels of blood pressure increases.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7811438
TI  - Factors related to the presence of microalbuminuria in essential hypertension.
AB  - The objective of the present study was to assess factors related to the presence
      of microalbuminuria in essential hypertension. Ninety-five patients with
      essential hypertension (58 males and 37 females, mean age 38.6 +/- 6.1 years) who
      had never been treated previously for hypertension were included in the study.
      Patients with nephropathy or diabetes mellitus, hyperglycemia > 120 mg/dL,
      glomerular filtration rate < 80 mL/min/1.73 m2, urinary tract infection, or
      positive dipstick for albumin or glucose were excluded. Blood pressure,
      echocardiographically determined left ventricular mass, serum biochemistry, and
      lipid profile were obtained. Twenty-four-hour urinary albumin excretion (UAE) was
      measured on two separate days using an immunonephelometric assay.
      Microalbuminuria (UAE 30 to 300 mg/24 h) occurred in 26% of patients and was
      associated with higher diastolic blood pressure (DBP), left ventricular mass
      index (LVMI), and a higher prevalence of hypertriglyceridemia and
      hyperapolipoproteinemia B (apo-B). Logistic regression analysis showed that the
      risk of microalbuminuria was independently related to diastolic blood pressure
      and hypertriglyceridemia when controlling for age, sex, body mass index, LVMI,
      and apo-B. Multiple regression analysis likewise confirmed that both DBP and LVMI
      were linearly related to UAE independent of age, sex, body mass index, total
      cholesterol, triglycerides, and apo-B. In conclusion, our study indicates that
      among hypertensive patients with elevated excretion rates of urinary albumin,
      even at the subclinical level, an increased cardiovascular risk exists compared
      to normoalbuminuric patients with a similar blood pressure. Assessment of the
      presence of microalbuminuria may be useful in the evaluation and management of
      hypertension.

PMID- 7811439
TI  - Urinary albumin excretion and nocturnal blood pressure in hypertensive patients
      with type II diabetes mellitus.
AB  - The aim of this study was to evaluate the relationship between nocturnal blood
      pressure (BP) (by ambulatory blood pressure monitoring, ABPM) and urinary albumin
      excretion (UAE) in hypertensive patients with type II diabetes mellitus. We
      studied 179 essential hypertensives (WHO I-II), all males, with non-insulin
      dependent diabetes. Non-invasive ABPM was performed by a fully automatic,
      portable device (Spacelabs 90202), set to take readings at 15-min intervals
      during both day-time 7 AM to 1 PM and nighttime (1 PM to 7 AM). According to the
      day/night reduction in mean blood pressure (MBP), three groups were identified:
      group I, nocturnal MBP reduction > 10%; group II, day/night MBP reduction of 5%
      to 10%; and group III, day/night MBP reduction < 5%. The mean values of UAE as
      well as the prevalence of microalbuminuria (UAE > 30 mg/24 h) were found to be
      significantly higher in group III as compared to the other two groups. Besides,
      in group III UAE displayed a significant negative relationship with the SBP and
      MBP (but not DBP) nocturnal drop and a positive relationship with the duration of
      hypertension and duration of diabetes. In group II, UAE was weakly correlated
      only with the duration of hypertension, whereas in group I no significant
      correlation was found between UAE and other parameters of the study. These
      results indicate that in hypertensive type II diabetic patients a blunted
      nocturnal BP fall is associated with higher UAE and increased prevalence of
      microalbuminuria. Whether the reduced day/night BP difference is the cause of
      consequence of target organ damage remains to be established.

PMID- 7811440
TI  - Prevention and Treatment of Hypertension Study (PATHS). Rationale and design.
AB  - Alcohol consumption has been recognized as an important correlate of blood
      pressure in many epidemiologic studies, but few interventional studies have been
      conducted to examine the effect of a reduction in alcohol intake on blood
      pressure. Because these studies have usually included few subjects and been of
      short duration, the National Heart, Lung, and Blood Institute (NHLBI), the
      National Institute on Alcohol Abuse and Alcoholism (NIAAA), and the Veterans
      Affairs (VA) Cooperative Studies Program have initiated a randomized, controlled,
      multicenter trial to determine whether blood pressure and left ventricular mass
      are lowered over 6 months of alcohol moderation in non-dependent moderate to
      heavy drinkers (three or more drinks per day average but not alcohol dependent)
      with above-average normal (80 to 89 mm Hg) and mildly hypertensive (90 to 99 mm
      Hg) levels of diastolic blood pressure, and whether a reduction in alcohol intake
      can be maintained for 2 years. Eligible veterans are randomized to either an
      alcohol reduction intervention or a control observation group at seven clinical
      sites. The projected sample size is 580 participants. Alcohol intake is assessed
      by self-report using a retrospective diary (Chronological Drinking Record) and by
      various biochemical markers, including apolipoproteins, HDL cholesterol (and
      subfractions), and carbohydrate deficient transferrin, analyzed at a central
      laboratory. The alcohol intervention technique is a cognitive-behavioral program,
      the intensive phase of which consists of six counseling sessions over 3 months.
      Echocardiograms are obtained at baseline and 6 months after randomization. This
      trial has important implications for both the prevention and treatment of
      hypertension.

PMID- 7811441
TI  - Effect of regression to the mean in serial echocardiographic measurements of left
      ventricular mass. Quantification and clinical implications.
AB  - When a study sample is selected on the basis of an increased value of a given
      parameter, subsequent serial measurements are likely to show a decrease in this
      measured parameter, that is, the "regression to the mean." This statistical
      phenomenon undoubtedly affects the results of echocardiographic follow-up
      studies. Its magnitude is linked to that of the intraindividual variability of
      the measurements. Therefore, we undertook a prospective study aimed at assessing
      the different components of the variability of repeated measurements of left
      ventricular (LV) mass index. For this purpose, 25 consecutive patients underwent
      two echocardiograms 2 weeks apart. An analysis of variance for the nested design
      (random-effect model) was performed: inter- and intraindividual variabilities
      accounted for 70% and 30% of the total variability, respectively. Moreover, the
      contribution of the readings to the total variability did not exceed 2%, whereas
      the contribution of both recordings and time reached 28%. Further calculations
      allowed the expected magnitude of the regression to the mean to be quantified
      according to the baseline left ventricular mass index. For instance, when
      patients are selected on the basis of an increased LV mass index with a mean
      baseline value of 150 g/m2, a spontaneous decrease of 12% (related solely to the
      regression to the mean) has to be expected for the following measurement.
      Accordingly, the results of open uncontrolled echocardiographic follow-up studies
      should be reevaluated: an adjustment for the potential influence of the
      regression to the mean has to be done.

PMID- 7811442
TI  - Quantification of global and regional renal blood flow with electron beam
      computed tomography.
AB  - Alterations in renal blood flow distribution may occur in a variety of
      pathophysiologic situations; however, quantification of global and regional renal
      blood flows has been limited because of the lack of reliable, noninvasive
      techniques. To determine the feasibility of flow measurements with electron-beam
      computed tomography (EBCT), six anesthetized dogs were scanned by EBCT during
      basal conditions, after renal vasodilation, and at recovery. Flow (mL/min/cm3
      tissue) was calculated from EBCT-derived time-density curves using three
      different algorithms and compared with simultaneously obtained electromagnetic
      flow (EMF) probe measurements after indexing to EBCT-derived renal volume. EBCT
      determined flow correlated well with EMF measurements regardless of the algorithm
      used. An algorithm using the area under the time-density curve was concluded to
      be the most suitable for calculation of renal blood flow; it correlated with EMF
      as EBCT flow = 44.5 + 1.05 EMF (r = 0.885, SEE = 31.2 mL/min, P < .0001).
      Consistent overestimation of flow by EBCT resulted probably from retention of
      contrast media in the renal parenchyma. EMF showed an increase of 20 +/- 10% in
      renal blood flow after vasodilation. EBCT-derived global, cortical, and medullary
      flows increased by 33.8 +/- 10.3%, 24.8 +/- 17.8%, and 99.0 +/- 73.8%,
      respectively. In conclusion, EBCT was found feasible for credible quantitation of
      renal blood flow in the physiologic range studied.

PMID- 7811443
TI  - Ambulatory blood pressure monitoring during pregnancy. Establishment of standards
      of normalcy.
AB  - Ambulatory blood pressure monitoring (ABPM) was used as an effective methodology
      by a primary care physician to assess normalcy of blood pressure (BP) and heart
      rate during pregnancy. One hundred fifty pregnant women in one of three periods
      (18 to 22, 30 to 32, and 36 to 38 weeks) of gestation and 30 age-matched
      nonpregnant women participated in this study. The study was designed to establish
      ABPM standards of normalcy during critical times of gestation. Twenty-four-hour
      BP (systolic and diastolic BP) values monitored during gestational weeks 18 to 22
      and 30 to 32 were similar to each other and lower than the same values recorded
      in nonpregnant women. Blood pressures monitored during gestational weeks 36 to 38
      were significantly higher than similar values observed during the two earlier
      gestational periods but not significantly higher than nonpregnancy BP values.
      Heart rates were significantly elevated during all gestational periods when
      compared with nonpregnancy heart rates. The results of this study established
      normalcy BP curves during three different gestational periods. Mean 24-h,
      daytime, and nighttime BPs were significantly elevated during weeks 36 to 38 when
      compared with BPs recorded during gestational weeks 18 to 22 and 30 to 32.
      Ambulatory blood pressure monitoring is a useful tool for the measurement and
      treatment of BP abnormalities during pregnancy.

PMID- 7811444
TI  - Nighttime dosing of doxazosin has peak effect on morning ambulatory blood
      pressure. Results of the HALT Study. Hypertension and Lipid Trial Study Group.
AB  - In this study the effects of a single daily dose (average 8.9 mg) of doxazosin
      (an alpha-adrenergic blocker) given at night were evaluated in 111 patients with
      mild hypertension. Patients were studied first on no medication, and a second
      time after being treated for up to 16 weeks with doxazosin. Blood pressure was
      measured by noninvasive ambulatory monitoring at the beginning and end of the
      study. There was a sustained reduction of both systolic and diastolic pressure
      throughout the day and night, but the greatest reduction occurred in the morning
      hours. Since the peak treatment effect was later than predicted from previous
      pharmacokinetic studies, it is suggested that the timing of the peak effect may
      depend on the prevailing level of alpha-adrenergic tone, as well as on the
      pharmacokinetics of the drug.

PMID- 7811445
TI  - Differential effects of doxazosin on clinic and ambulatory pressure according to
      age, gender, and presence of white coat hypertension. Results of the HALT Study.
      Hypertension and Lipid Trial Study Group.
AB  - In this study the effects of a single daily dose of doxazosin (an alpha
      adrenergic blocker) given at night were evaluated in 112 patients with mild
      hypertension. Patients were studied first on no medication, and a second time
      after being treated for up to 16 weeks with doxazosin. Blood pressure (BP) was
      measured by noninvasive ambulatory monitoring at the beginning and end of the
      study. Before treatment, the white coat effect (clinic-ambulatory BP) was greater
      in women than in men (significant for systolic pressure but not diastolic), and
      greater in elderly (aged over 65 years) than in younger patients (significant for
      both systolic and diastolic pressure). Clinic and ambulatory BP were reduced to a
      similar extent in men and women by doxazosin, but in the elderly the fall in
      clinic BP was associated with a much smaller fall of ambulatory BP. In patients
      with white coat hypertension (elevated clinic but normal ambulatory BP) doxazosin
      lowered clinic but not ambulatory BP, while in those with sustained hypertension
      it lowered both.

PMID- 7811446
TI  - Doxazosin studies provide clearer picture of blood pressure profiles.

PMID- 7811447
TI  - Olecranon bursitis associated with 24-hour ambulatory blood pressure monitoring.

PMID- 7811448
TI  - [Attempted fraud in legal identity determination--detection by DNA single locus
      analysis].
AB  - In a case where a mix up of blood samples was claimed, an identity check was
      carried out by means of four single-locus-probes. DNA analysis produced identical
      profiles with two of the probes (MS 31 and MS 43). With the two other probes one
      matching and one differing fragment could be detected respectively (MS 1 and g3)
      In addition to the unambiguous statement "no identy", the DNA analysis proved
      that the tested blood samples must have been those of two closely related people,
      most probably of brothers and sisters. Attempted fraud can be assumed from these
      findings. Further investigations and additional DNA analysis which included a
      blood sample of the brother of the accused, revealed that the sample for the
      identity check had been taken from the brother and not from the accused himself.

PMID- 7811449
TI  - [A correlation between level of blood alcohol and repeated offense].
AB  - Statistical analysis of 46,972 recorded blood samples and the relevant BAC
      classification revealed the following points: 1. A correlation between the BAC
      level at the time of the first offence and the probability of a recurrence could
      not be proved. 2. Most recurrences took place within three years. 3. The
      probability of a recurrence rises with the number of offences.

PMID- 7811450
TI  - [Medical psychologic studies of drunken drivers. A critical discussion to the
      contribution by Jansen and Utzelmann in Blutalkohol 31, 249-259, 1994].
AB  - I am replying to the critical analysis by Jansen and Utzelmann of one of my
      essays (Blutalkohol 30, 65-95, 1993). I reject their arguments; this underpins,
      once again, the unsatisfactory prognosis of expert opinion on DWI-offenders.
      Emphasis should be placed on general preventive measures with rules for behaviour
      rather than on efforts of assessing the driver's personality, which seems more
      just only at first sight.

PMID- 7811451
TI  - [Human behavior between instinct, feelings and responsibility].
AB  - The paper deals with the fundamental problem: How does the brain (in the way it
      is and the way it functions) influence human experience, behaviour and social
      interaction? Deriving from this question, there's the matter of how all this
      influences people as road users. After some epistemological considerations the
      following subjects are dealt with the article: the human perception and human
      "reality", the limits of human imagination, the basis of human learning, the
      complexity of processes within the brain, the reaction to changes and the ability
      to concentrate as well as McLean's theory of the triune brain. The subjects are
      complemented by aspects of biological and socio-cultural evolution of man,
      starting from evolutionary ethics going right up to the problem of
      responsibility.

PMID- 7811452
TI  - [Alcohol related accidents and revoking the driving license for alcohol-induced
      traffic violations in Germany 1975-1993].
AB  - The Federal Office for Statistics and the Federal Office for Motor Vehicles made
      some statistics available on the development of accidents due to alcohol on
      German streets and the withdrawal of driving licences due to criminal offences
      involving drinking and driving in Germany from 1975 to 1993. These statistics are
      evaluated so that a connection between the accidents and the withdrawal of
      driving licences can be worked out. This evaluation showed that in the long run
      both the number of accidents caused by the influence of alcohol and the
      withdrawal of driving licences due to drinking and driving are falling in
      Germany.

PMID- 7811453
TI  - Susceptibility of the Sf9 insect cell line to infection with adventitious
      viruses.
AB  - Sf9, the insect cell line commonly used for gene expression by recombinant
      baculovirus (BV), can be infected by St. Louis encephalitis (SLE) virus, a
      flavivirus, resulting in a persistent, productive, and cytopathic infection,
      while retaining the ability to be infected with a recombinant baculovirus (rBV).
      We now demonstrate using double immunofluorescence that single cells are dually
      infected with SLE virus and rBV. Fourteen additional viruses including additional
      flaviviruses, other arbovirus classes, vesicular stomatitis virus (VSV), and
      herpes simplex virus, type 1 (HSV-1) failed to produce a cytopathic effect (CPE)
      in Sf9 cells. Plaque assays indicated infectious virus was present for several
      weeks post-inoculation for Yellow fever (YF), Dengue types 1 and 2 (DEN-1 and DEN
      2), Gumbo limbo (GL), Eastern equine encephalomyelitis virus (EEE), Western
      equine encephalomyelitis virus (WEE), HSV-1, and VSV viruses. For HSV-1, GL, EEE,
      WEE and VSV, but not for YF, DEN-1 or DEN-2 viruses, this could be attributed
      solely to survival in the Sf9 cell culture media. Of the 14 viruses tested, only
      HSV-1 could be detected after 2 weeks in serum-free media. The data indicate that
      several viruses which are pathogenic for humans are stable for long periods of
      time at 27 degrees C in the serum-containing media used for cultivation of Sf9
      cells. YF, DEN-1 and DEN-2 viruses may replicate in Sf9 cells at extremely low
      levels. This suggests that adventitious agents which do not produce obvious CPE
      or interfere with rBV infection or recombinant protein expression could
      contaminate Sf9 cell cultures or media.

PMID- 7811454
TI  - Comparative analysis of tetanus antitoxin titers of sera from immunized mice and
      guinea pigs determined by toxin neutralization test and enzyme-linked
      immunosorbent assay.
AB  - Enzyme-linked immunosorbent assay (ELISA) and toxin neutralization (TN) test were
      comparatively evaluated for determination of antibodies to tetanus toxin in sera
      of immunized guinea pigs and mice at different intervals. Tetanus specific IgG
      antibodies by ELISA were found in sera of guinea pigs at ninth day after
      inoculation and in mice sera at seventh day after inoculation when there were no
      TN antibodies. Two weeks after injection of mice with aluminium phosphate
      adsorbed tetanus toxoid, anti-tetanus toxin IgG levels determined by ELISA were
      35 to 40 times higher than the TN titers. At 4 weeks, ELISA IgG antibody levels
      of mice and guinea pig sera were still statistically significantly higher than TN
      titers but with a good correlation between ELISA and TN titers (correlation
      coefficient of mice sera 0.89). Mice sera at 2 weeks after two doses of tetanus
      toxoid (interval between doses 30 days) and 8 weeks after a single injection
      showed similar ELISA and TN titers (P > 0.1). Guinea pig sera at 6 weeks after a
      single injection showed similar TN and ELISA titers (P > 0.4). During the course
      of immunization in mice and guinea pigs, low avidity and low affinity IgG
      antibodies start appearing early which are detected by ELISA but not by TN test.
      Therefore ELISA results on sera before 6 weeks of immunization determined against
      a hyper-immune reference serum do not give a true picture of TN levels.

PMID- 7811455
TI  - The consistent use of organic solvents for purification of phospholipids from
      brain tissue effectively removes scrapie infectivity.
AB  - A procedure for the purification of phospholipids from brain tissue was evaluated
      for its efficacy in eliminating scrapie agent infectivity. The key feature of the
      process was that phospholipids were extracted and purified by exclusive use of
      organic solvents. Experiments were done by in vivo animal bioassay on a scaled
      down version of the original procedure using 263 K-infected hamster brains as
      source material. The absence of any detectable infectivity in the final
      preparations indicated that organic solvent extraction is acceptable for
      purification and decontamination of biological products from scrapie-like agents
      provided that only the organic phase is used.

PMID- 7811456
TI  - Rapid inactivation of HIV-1 in single donor preparations of human fresh frozen
      plasma by methylene blue/light treatment.
AB  - Human fresh frozen plasma (FFP) was spiked with highly titered HIV-1 and
      illuminated with visible light in the presence of 1 microM of the photoactive dye
      methylene blue (MB). As shown by titration on MT-4 cells, the infectivity of the
      virus containing plasma was rapidly lost during illumination: after 5 min the
      infective titer was reduced by 4.3 and after 10 min by at least 6.32 log10, i.e.
      it was below the detection limit of the assay applied. Methylene blue without
      illumination and illumination alone had only a marginal effect on HIV-1
      infectivity. Thus our data indicate that the MB/light treatment of FFP is an
      effective method to eliminate the risk of HIV-1 infection through use of the
      product. This is especially important for those cases in which the plasma is
      collected during the 'window period' between infection of the donor and the
      subsequent seroconversion.

PMID- 7811457
TI  - Development of pertussis serological potency test. Serological assessment of
      antibody response induced by whole cell vaccine as an alternative to mouse
      protection in an intracerebral challenge model.
AB  - The current potency test for pertussis vaccines, the mouse protection test (MPT),
      has many disadvantages. However, no alternative is yet available. The purpose of
      this study is to develop a serological alternative for the MPT based on in vitro
      assessment of the humoral immune response against pertussis in mice. After
      immunization with pertussis whole cell vaccine, the MPT shows a normal primary
      and secondary antibody response. Moreover, the i.c. challenge has a distinct
      booster effect on the pertussis IgG response. The relationship between the
      concentration of IgG antibodies against the surface-antigens of pertussis
      bacteria and the survival of mice after the i.c. challenge was demonstrated in a
      modified MPT (R = 0.91). To this end a protecting antibody level of > or = 45
      EU/ml was selected as a level at which concentration most of the mice survived.
      Survival of mice in the MPT could be predicted, based on the antibody
      concentration at the day of challenge. Potencies estimated with the predicted and
      actual survival corresponded well (P = 0.990). This confirmed the essential role
      of vaccine induced pertussis antibodies in the protection against a lethal i.c.
      challenge and offered a possibility to develop a pertussis potency test based on
      serology. We developed a model in which mice (20-24 g) are immunized (i.p.) with
      graded doses of vaccine and bled after four weeks. Sera are titrated in
      Bordetella pertussis whole cell ELISA and potency based on vaccine dose dependent
      antibody response is estimated by means of a parallel line analysis. The potency
      of vaccines tested in the Pertussis Serological Potency Test (PSPT) and MPT are
      significantly similar, a P-value of 0.92 was found by means of the chi 2 test.
      Compared to the MPT, the PSPT is more reproducible as is indicated by its smaller
      95% confidence intervals. Moreover, by using the PSPT the animal distress can be
      reduced to an acceptable level and the PSPT also results in a reduction of more
      than 25% in use of mice.

PMID- 7811458
TI  - Increased levels of active pertussis toxin may aid a pertussis vaccine to pass
      the mouse body weight gain test.
AB  - The mouse weight gain test was evaluated for its value in toxicity testing for
      pertussis vaccines. When the reference whole cell pertussis vaccine was tested at
      dilutions of 1 in 1 and 1 in 16, the mice which received the 1 in 1 dilution
      achieved the greatest weight gain by the seventh day of injection, although they
      experienced a more significant weight loss during the first 24 hours than both
      the normal control mice or those that received the 1 in 16 dilution. A commercial
      diphtheria-tetanus-acellular pertussis vaccine with an increased level of
      pertussis toxin activity significantly accelerated the weight gain of mice. The
      effect was lost by heating the vaccine at 80 degrees C for 2 hours. A 1
      micrograms dose of endotoxin induced a significant weight loss in mice during the
      first 24 hours of injection followed by weight gain at the same rate as that of
      the normal control. Pertussis toxin accelerated the weight gain of mice at a dose
      of 2 micrograms to a level exceeding that of the normal control mice throughout
      the observation period of 11 days. Pertussis toxin, when inoculated with
      endotoxin, showed a marked effect of helping mice to recover quickly from the
      endotoxin-induced initial weight loss to the level of those receiving only
      pertussis toxin. The effect of pertussis toxin on the acceleration of the weight
      gain of mice showed the possibility of inappropriate interpretation of the test
      results. It suggests, therefore, the necessity for separate quantitative tests
      for controlling the vaccine's toxicities.

PMID- 7811459
TI  - Calibration of a replacement preparation for the International Standard for
      Rabies Immunoglobulin.
AB  - A proposed replacement preparation for the International Standard for Rabies
      Immunoglobulin was calibrated by means of two assay methods, a neutralization
      test in mice (MNT) and a neutralization test in cell culture (RFFIT). The
      calibration was made as an international collaborative assay comprising nine
      laboratories in eight countries. The results obtained in this study confirm
      earlier observations about occasional unexplainable differences between relative
      potencies obtained by the two methods. They also confirm the apparent reliability
      of the RFFIT. Based on the results obtained the proposed replacement preparation
      has been established as the second International Standard for Rabies
      Immunoglobulin with a defined unitage of 30 International Units of Rabies
      Antibodies in each ampoule.

PMID- 7811461
TI  - Workshop on safety of plasma donation. Blood Products Advisory Committee of the
      Centre for Biologicals Evaluation and Research (CBER) Food and Drug
      Administration. Bethesda, Maryland, June 28-29, 1993.

PMID- 7811460
TI  - Interlaboratory validation of in vitro serological assay systems to assess the
      potency of tetanus toxoid in vaccines for veterinary use.
AB  - An interlaboratory validation study was carried out in seven laboratories to
      evaluate the suitability of in vitro serological assay systems for the assessment
      of the potency of tetanus toxoid in single and multicomponent vaccines for
      veterinary use. Nine commercial vaccines and one experimental tetanus toxoid
      preparation were selected for immunization purposes according to Method A of the
      European Pharmacopoeia. Levels of tetanus antibodies in guinea-pig and rabbit
      serum samples were estimated by indirect ELISA, toxin binding inhibition (ToBI)
      test, passive haemagglutination (HA) test and by the prescribed standard toxin
      neutralization (TN) test in mice. Estimates of potency obtained by in vitro tests
      and by TN test were in good agreement for the various vaccines tested and for
      antibody levels of individual serum samples in the range 2.6 IU/ml to 266 IU/ml.
      Significant (P < 0.05) intralaboratory variation occurred less frequently for
      ELISA and ToBI test than for HA test. The frequency of significant (P < 0.05)
      interlaboratory variation was acceptable for the ELISA and the ToBI test but
      greater variation was observed for the HA test. It is concluded that the ELISA
      and ToBI tests are suitable in vitro assay systems for assessing the potency of
      tetanus toxoid in batches of single and multicomponent vaccines for veterinary
      use. Rigid standardization of the HA test is essential before this test can be
      used for the same quality control purpose.

PMID- 7811462
TI  - Second European Conference on Vaccinology. Combined vaccines for Europe:
      pharmaceutical, regulatory and policy making aspects.

PMID- 7811463
TI  - 5th International Congress on Tumour Necrosis Factor and Related Cytokines:
      Scientific Advances and their Medical Applications.

PMID- 7811464
TI  - Cell adhesion molecules in asthma: homing, activation, and airway remodeling.

PMID- 7811465
TI  - Regulation of monocyte chemoattractant protein-1 gene expression and secretion in
      rat pulmonary alveolar macrophages by lipopolysaccharide, tumor necrosis factor
      alpha, and interleukin-1 beta.
AB  - Chemotactic cytokines coordinate the recruitment of leukocytes into the lung
      during pulmonary inflammation. In a previous study, we determined that rat
      pulmonary alveolar macrophages (PAMs) facilitate monocyte recruitment and
      activation in the lung during acute inflammatory lung injury, in part, through
      the inducible expression of monocyte chemoattractant protein-1 (MCP-1). MCP-1 is
      an 11 to 15 kD basic peptide that specifically mediates monocyte chemotaxis and
      activation. Inflammatory mediators that regulate the expression and secretion of
      MCP-1 by rat PAMs have not been identified. We determined that stimulation of
      resident rat PAMs with bacterial lipopolysaccharide (LPS), murine tumor necrosis
      factor-alpha, or human interleukin-1 beta resulted in the inducible expression of
      MCP-1 mRNA and the secretion of biologically active MCP-1. In contrast, phorbol
      myristate acetate, a nonphysiologic leukocyte activator, was significantly less
      effective in stimulating either enhanced MCP-1 mRNA expression or secretion of
      MCP-1. These results indicate that the expression of MCP-1 mRNA and the secretion
      of MCP-1 by rat PAMs are regulated by bacterial products (LPS) and inflammatory
      cytokines. Further, these results suggest PAMs are regulated by bacterial
      products (LPS) and inflammatory cytokines. Further, these results suggest that
      resident PAMs, through elaboration of MCP-1, may play a pivotal role in
      regulating recruitment and activation of monocytes in the lung during acute
      inflammatory lung injury.

PMID- 7811466
TI  - Expression of pulmonary surfactant protein D in rat gastric mucosa.
AB  - Gastric mucosa is protected from an acidic lumenal environment by an
      extracellular layer composed in part of phospholipids that are similar in
      composition to the phospholipids of lung surfactant. The function and metabolic
      processing of lung surfactant is regulated, in part, by surfactant specific
      proteins. We speculated that the gastric extracellular acid barrier might be
      regulated by such proteins. We demonstrate by RNA blot analysis, RT-PCR, and
      immunostaining and protein blot the synthesis of surfactant protein D (SP-D) in
      mucus-secreting cells of the gastric mucosa. SP-D protein and mRNA were not
      detected in the duodenum and the remainder of the gastrointestinal tract. We
      speculate that SP-D may participate in the regulation of secretion or assembly of
      the gastric acid barrier. Alternatively, SP-D may participate in gastric mucosal
      host defense.

PMID- 7811467
TI  - In vivo hyperoxic exposure increases cultured lung fibroblast proliferation and c
      Ha-ras expression.
AB  - Exposure to hyperoxia has been demonstrated to alter the cell number of lung
      fibroblasts in vivo. The precise mechanism of lung fibroblast proliferation after
      hyperoxic exposure has not been elucidated, however. We examined the growth
      characteristics of lung fibroblasts isolated from 21-day-old rats exposed to air
      or 100% O2 for 8 days. Cell proliferation was assessed by hemocytometry,
      [3H]thymidine incorporation, and fractional labeling with the thymidine analog
      bromodeoxyuridine. Under all conditions tested, fibroblasts isolated from O2
      exposed rats grew more rapidly than those from air-exposed rats. Conditioned
      medium from fibroblasts isolated from hyperoxia-exposed rats failed to increase
      the [3H]thymidine incorporation of control cells to that observed in cells
      isolated from hyperoxia-exposed animals, suggesting that an autocrine growth
      factor was not responsible for the excess proliferation. Sensitivity to exogenous
      growth factors was assessed by measuring the response to increasing
      concentrations of insulin-like growth factor-1 (IGF-1). Relative to 1% fetal
      bovine serum (FBS), concentrations of IGF-1 between 3 and 30 ng/ml significantly
      increased the [3H]thymidine incorporation of fibroblasts derived from hyperoxic
      animals, whereas control cells were unresponsive to IGF-1 stimulation. The
      apparent sensitivity to IGF-1 led us to assess the effect of in vivo hyperoxic
      exposure on the expression of c-Ha-ras, which encodes a membrane-bound, GTP
      binding/hydrolyzing protein essential for progression through G1 in the cell
      cycle. ras mRNA levels in quiescent, control cells were minimal but increased
      following serum stimulation. The c-Ha-ras expression of lung fibroblasts from
      hyperoxia-exposed animals, on the other hand, was substantial in quiescent cells
      and remained high after serum exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7811468
TI  - Cloning and expression of the alveolar type II cell P2u-purinergic receptor.
AB  - Adenosine triphosphate (ATP) regulates surfactant phospholipid secretion from
      alveolar type II cells by interacting with P2-purinoceptors on the alveolar type
      II cell surface. To further characterize regulation of surfactant secretion, we
      have cloned the type II cell P2u-purinoceptor and expressed a functional receptor
      in an unrelated cell line. The coding sequence of the P2u clone isolated from a
      type II cell cDNA library was 1.1 kb, encoding a putative protein of 374 amino
      acids. The putative protein demonstrated > 97% homology with the P2u-purinoceptor
      previously identified in the hybrid neuroblastoma x glioma cell line, NG 108-15,
      87% homology to the recently cloned human P2u-purinoceptor, and 34% homology to
      the P2u-purinoceptor cloned from chicken brain. The putative type II cell P2u
      protein contains seven membrane-spanning domains, characteristic of G-protein
      coupled receptors. The type II cell P2u-purinoceptor nucleotide sequence also
      demonstrated > 95% homology to the nucleotide sequence of the NG 108-15 clone.
      However, the type II cell cDNA also demonstrated presence of an additional 208 bp
      insert in the 5' untranslated region, which was not present in the NG 108-15
      clone. Using reverse transcriptase polymerase chain reaction, we examined
      expression of the two different sizes of mRNA in various rat tissues. Only the
      larger type II cell mRNA was expressed in rat heart, kidney, lung, spleen, and
      testis, with no expression of P2u-purinoceptor mRNA noted in brain or liver. The
      smaller species of mRNA was only detected in mouse N18-TG2 cells, and these cells
      expressed a larger species as well, found in the rat tissues noted.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7811470
TI  - Rat serum inhibits progression of alveolar epithelial cells toward the type I
      cell phenotype in vitro.
AB  - Serum contains a number of polypeptide growth factors, hormones, and soluble
      matrix components and may influence the state of differentiation of epithelial
      cells in general and of alveolar epithelial cells (AEC) in particular. To
      evaluate the influence of sera on the transition from the type II toward the type
      I cell phenotype, we compared the effects of newborn bovine serum (NBS) and rat
      serum (RS) on morphologic changes and expression of a type I cell-specific
      epitope in AEC monolayers with time in primary culture. Rat type II AEC were
      harvested and cultured in defined serum-free medium (MDSF), MDSF + RS (5%), or
      MDSF + NBS (10%). Monolayer integrity was monitored by measuring transepithelial
      resistance (approximately 2,000 omega.cm2) and short-circuit current
      (approximately 4 microA/cm2). Binding of the type I cell-specific monoclonal
      antibody VIIIB2 was assessed between day 1 and day 11 by cell-based enzyme-linked
      immunosorbent assay (ELISA) and by immunoelectron microscopy (IEM). By ELISA, in
      MDSF and MDSF + NBS, VIIIB2 binding increased markedly after day 2, rising
      approximately 4-fold by day 8 (compared with day 1). In dramatic contrast, there
      was essentially no increase in VIIIB2 binding through day 11 in MDSF + RS.
      Results from IEM for apical surface binding of VIIIB2 were similar to those
      obtained by ELISA. Some morphologic differences were also noted, with cells in
      MDSF + RS being somewhat less spread at later times than those in MDSF or MDSF +
      NBS. These data indicate that the rate of rat type II AEC differentiation toward
      the type I cell phenotype is significantly modulated by soluble factor(s) present
      in rat serum.

PMID- 7811469
TI  - Platelet-derived growth factor (PDGF)-AA, -AB, and -BB induce differential
      chemotaxis of early-passage rat lung fibroblasts in vitro.
AB  - Platelet-derived growth factor (PDGF) isoforms are chemoattractants and mitogens
      for cells of mesenchymal origin that could be important mediators of pulmonary
      fibrogenesis. We have previously reported that particle-activated alveolar
      macrophages secrete homologues of PDGF that are composed of all three PDGF
      isoforms (PDGF-AA, -AB, and -BB). This mixture of macrophage-derived PDGF, once
      dissociated from the PDGF-alpha-macroglobulin complex, induces chemotaxis of rat
      lung fibroblasts (RLF) in the nanomolar range. In addition, we have reported that
      PDGF isoforms induce differential proliferation of RLF (PDGF-BB > PDGF-AB > PDGF
      AA). In the present study, we sought to determine the relative chemotactic
      potency of the three PDGF isoforms and correlate these responses to the relative
      abundance of the two types of PDGF cell-surface receptors: PDGF-alpha receptor
      (PDGF-R alpha) and PDGF-beta receptor (PDGF-R beta). We also investigated the
      chemotactic activity of combinations of two PDGF isoforms simultaneously.
      Isolates of early-passage RLF were assayed for chemotaxis in 48-microwell
      chambers. Swiss mouse 3T3 cells were assayed in parallel as a positive control
      cell line for PDGF-R alpha and PDGF-R beta expression. RLF responded
      differentially to the PDGF isoforms: PDGF-AB and PDGF-BB were potent
      chemoattractants and stimulated maximal chemotactic responses between 4 and 8
      ng/ml PDGF, whereas PDGF-AA elicited a weak chemotactic response that was
      maximally 15% of that obtained with either B-chain isoform. PDGF-AB and PDGF-BB
      were also the most potent chemoattractants for Swiss 3T3 cells, and their
      response to these B-chain isoforms was approximately 40% greater than that
      obtained for RLF.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7811471
TI  - Comparative studies indicate that platelet-activating factor is a relatively weak
      eosinophilotactic mediator.
AB  - Eosinophils are important immune effector cells in a variety of allergic
      responses and inflammatory lung diseases. Bacterial products and inflammatory
      mediators have been implicated in inducing an influx of eosinophils into the
      respiratory tract subsequent to an acute inflammatory response. Therefore, to
      better understand the role of eosinophils in lung inflammation, we compared the
      ability of three known chemoattractants, formylmethionylleucylphenylalanine
      (FMLP), leukotriene B4 (LTB4), and platelet-activating factor (PAF), to induce
      human eosinophils to migrate across 3.0-microns-pore naked filters and human
      umbilical vein endothelial cells (HUVEC) and A549 human pulmonary type II-like
      epithelial (A549) cells cultured in monolayers on these filters. Kinetic
      experiments indicated that eosinophil migration through all three barriers
      occurred by 60 min and plateaued by 2 h. Each of these chemoattractants induced
      eosinophil migration in dose-responsive fashion across all three barriers.
      Although similar maximal eosinophil migration was observed, the doses at which
      this occurred varied, indicating that the rank order of potency through naked
      filters is FMLP > PAF > or = LTB4. However, their relative chemotactic potency
      through cellular barriers was different, with FMLP > LTB4 > PAF. In contrast to
      previous studies with neutrophils, the rank order of potency of the three
      chemoattractants was not influenced by the barrier through which the eosinophil
      migrated. Thus, these and previous data show that FMLP, LTB4, and PAF are
      eosinophil and neutrophil chemoattractants. Therefore, it is likely that these
      three agents are important mediators of granulocytic inflammatory responses in
      the lung, albeit with different potency profiles.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7811472
TI  - Contrasting effect of interleukin-13 on interleukin-1 receptor antagonist and
      proinflammatory cytokine production by human alveolar macrophages.
AB  - We investigated the effect of interleukin-13 (IL-13) on production of IL-1
      receptor antagonist (IL-1ra) and proinflammatory cytokines by human alveolar
      macrophages (AM). AM were obtained by bronchoalveolar lavage from healthy donors.
      The production of IL-1ra and proinflammatory cytokines, such as IL-1 beta, IL-6,
      and tumor necrosis factor-alpha (TNF-alpha), were quantitated by enzyme
      immunoassays. AM spontaneously produced IL-1ra, and this production was
      significantly augmented by IL-13. On the other hand, IL-13 alone did not affect
      production of proinflammatory cytokines by freshly isolated AM. Upon stimulation
      with lipopolysaccharide (LPS), AM produced a significantly amount of
      proinflammatory cytokines as well as IL-1ra, but this production was suppressed
      by IL-13 in a dose-dependent manner. In contrast, IL-13 caused a small but
      reproducible increase in LPS-induced IL-1ra production. These regulatory effects
      of IL-13 were also observed in blood monocytes and macrophages generated in vitro
      by maturation of blood monocytes with granulocyte/macrophage colony-stimulating
      factor. These observations suggest that IL-13 may act as an anti-inflammatory
      cytokine through regulation of cytokine production by AM in the lung.

PMID- 7811473
TI  - 5' splicing and allelic variants of the human pulmonary surfactant protein A
      genes.
AB  - Human pulmonary surfactant protein A (SP-A) is encoded by two genes, SP-A1 and SP
      A2. Reports from our laboratory and other investigations have shown heterogeneity
      in both genes within three regions (the 5' untranslated [5' UT], the coding, and
      the 3' untranslated [3' UT] regions). To more fully examine the variability in
      these regions and characterize the transcription start site in each gene, we used
      primer extension and 5' RACE to clone and then sequence cDNA clones from two
      individuals. These cDNAs extended from the transcription start site to
      approximately 40% of the 3' UT segment. The in vitro translatability of selected
      cDNAs was also tested. After analysis of our data, we found that: (1) the 5' UT
      of SP-A genes contains four (A, B, C, D for SP-A1) or three (A, B, D for SP-A2)
      untranslated exons, three of which (A, B, D) vary in length, and one of which (C)
      is new; (2) these exons are alternatively spliced and the major splice patterns
      as well as their relative frequency vary between the two genes (the major pattern
      for SP-A1 is AD'[81%] and the major patterns for SP-A2 are ABD [44%] and
      ABD'[49%]); (3) the SP-A1 gene uses three transcription start sites with equal
      frequency, whereas the SP-A2 gene uses only one; (4) splicing variability occurs
      among alleles and among individuals; (5) three previously undescribed alleles
      exist for the SP-A1 gene (6A2, 6A3, 6A4) and two for the SP-A2 gene (1A1, 1A2);
      and (6) a core group of 10 invariant nucleotides and four invariant amino acids
      can be used to discriminate between SP-A1 and SP-A2 alleles.

PMID- 7811474
TI  - Clearance of surfactant protein A from rabbit lungs.
AB  - Surfactant protein A (SP-A) is a major surfactant protein with multiple
      biophysical, metabolic, and host defense functions. To further characterize its
      metabolism in vivo, we measured clearance of SP-A from adult rabbit lungs. Trace
      amounts of [125I]SP-A radiolabeled by the Bolton-Hunter method and mixed with
      [3H]dipalmitoylphosphatidylcholine (DPPC) were given intratracheally via a
      bronchoscope to rabbits. Groups of five to six animals were studied 10 min to 16
      h after labeled surfactant administration. After collection of alveolar washes,
      lamellar bodies were isolated from lung tissue. Macrophages also were isolated
      from alveolar washes. [125I]SP-A was cleared more rapidly than DPPC from the
      airspaces. Both [125I]SP-A and [3H]DPPC were lost exponentially from the total
      lungs, with half-life values of 6.5 h for SP-A and 12 h for DPPC (P < 0.01). In
      macrophages, the highest radioactivities for SP-A and DPPC were at 10 to 45 min
      and the radiolabels subsequently disappeared similarly. In lamellar bodies, 125I
      and 3H radioactivities per mumol saturated phosphatidylcholine (Sat PC) increased
      in parallel and were highest at 2 h. Whereas radiolabeled lipids were recovered
      in lamellar bodies for up to 16 h, iodinated SP-A was lost, indicating less
      recycling of SP-A than DPPC. We previously showed independent pathways of SP-A
      and Sat PC secretion in rabbits. These results demonstrate the different
      clearance kinetics of these two principle components of surfactant.

PMID- 7811476
TI  - Lung cancer surgery in the octogenarian.
AB  - From 1981 through 1991, 40 patients 80 years of age or older underwent
      thoracotomy for curative resection of bronchogenic carcinoma. There were 22 males
      and 18 females with a mean age of 82.7 years (range 80-88). In three patients,
      the operation was aborted due to unexpected metastatic disease discovered at the
      time of thoracotomy. The remaining 37 patients underwent 5 pneumonectomies, 26
      lobectomies and 6 segmentectomies or wedge resections. Three of these patients (1
      pneumonectomy, 1 lobectomy, and 1 wedge resection) underwent concomitant en bloc
      chest wall resection. The overall operative mortality rate (in hospital or within
      30 days) was 15% (6/40) while there was a 16% mortality rate (6/37) for resected
      patients. Complications occurred in 18 of 40 patients (45%) but were major in
      only 12 (30%). Major complications included respiratory insufficiency (6),
      pneumonia (4), prolonged air leak (2), stroke (1), urinary retention
      prostatectomy (1), and one unexplained sudden death 2 weeks following discharge.
      Postoperative stay in the 34 operative survivors averaged 14 +/- 8.8 days (range
      3-47). Univariate analysis revealed that neither gender, extent of lung
      resection, preoperative NYHA class, history of heart disease nor chronic
      obstructive pulmonary disease (COPD) were predictive of operative mortality in
      the 37 patients undergoing lung resection. Age was the only predictor of
      mortality (survivors 82.2 +/- 2.2, non-survivors 84.3 +/- 2.6; P < 0.05). The
      need for chest wall resection approached but did not quite achieve significance
      (P < 0.08). Actuarial survival for all 40 patients at 1 and 3 years is 55% and
      40%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7811475
TI  - Differential expression of cyclin D2 and cdc2 genes in proliferating and
      nonproliferating alveolar epithelial cells.
AB  - Alveolar epithelial cells (AEC) proliferate during embryonic and fetal life,
      while in the adult lung AEC form a highly differentiated population that does not
      usually divide. Herein, we tested the hypothesis that differential expression of
      specific cell cycle control genes may occur during AEC development and
      transformation. We compared normal rat AEC in primary culture with transformed
      AEC for the expression of D-type G1 cyclins and cyclin-dependent protein kinases
      (cdc2 and cdk2). Cyclin D1 mRNA and protein were expressed at comparable levels
      in both normal rat AEC and in transformed AEC. In contrast, high levels of cyclin
      D2 mRNA and protein expression were only observed in normal 19-day fetal rat AEC
      and in transformed mink Mv1Lu cells derived from fetal mink lung epithelium.
      Moreover, treatment either with antisense oligodeoxynucleotides directed against
      cyclin D2 mRNA or with genistein (a tyrosine kinase inhibitor) caused significant
      inhibition of [3H]thymidine incorporation into DNA as well as inhibition of
      cyclin D2 expression in normal 19-day fetal rat AEC. p34cdc2 (but not p33cdk2 or
      p34cdk4) was expressed at progressively decreasing levels with corresponding
      histone H1 kinase activities during rat AEC development (19-day fetal > 21-day
      fetal > 13-day postnatal > adult rat AEC). The levels of p34cdc2 histone H1
      kinase activity were significantly up-regulated or amplified in adult rat type 2
      AEC following hyperoxic injury and repair and in transformed AEC. Collectively,
      these data support an important functional role for cyclin D2 and cdc2 genes in
      determining the proliferative versus nonproliferative phenotype of AEC during
      lung development, injury and repair, and transformation.

PMID- 7811477
TI  - Surgery following neoadjuvant MPV chemotherapy (mitomycin, cisplatin,
      vinblastine) in locally advanced (IIIa and IIIb) non-small cell lung cancer.
AB  - From November 1990 to August 1993, 32 patients with non-small cell lung cancer
      (NSCLC) entered a multimodality treatment study with neoadjuvant Mitomycin,
      Cisplatin and Vinblastine (MPV), surgery and radiotherapy at the San Raffaele
      Hospital in Milan, Italy. Neoadjuvant chemotherapy was performed on an outpatient
      basis. To date 23 patients (11 stage IIIa and 12 stage IIIb) have completed the
      chemotherapy treatment and are available for evaluation of response, toxicity,
      surgical eligibility and resection rate. The overall major response to MPV
      chemotherapy was 87%. The overall resection rate after major response to
      treatment was 60% (90% in stage IIIa and 17% in stage IIIb). After a median
      follow-up of 21 months (8-31) 17 patients are still alive (74%). Ten patients
      (83%) who had a complete resection are alive after a median follow-up of 23
      months (21-30) and eight of them (66%) are in complete pathological remission. No
      treatment-related mortality was observed. The authors conclude that MPV is a
      highly effective neoadjuvant regimen for NSCLC and is feasible on an outpatient
      basis. Favorable resection rates can be obtained in stage IIIa patients. Stage
      IIIb patients can be downstaged and undergo complete resection. A longer follow
      up is needed to assess the impact of this multimodality approach on long-term
      survival and to evaluate the role of adjuvant radiotherapy.

PMID- 7811478
TI  - Should cardiac transplantation for congenital heart disease be delayed until
      adult age?
AB  - The number of pediatric heart transplantations for complex congenital heart
      disease has increased over the last years, but little experience has been
      reported in adolescent and adult populations. Between 1987 and 1992, 14 patients
      (mean age 33.2 years, range 14 to 51 years) were transplanted in our institution
      because of structural congenital heart disease (n = 9) or other rare disorders of
      the endomyocardial morphogenesis (n = 5). The main diagnosis included
      transposition of the great arteries, congenitally corrected transposition of the
      great vessels, left superior vena cava, tricuspid atresia with right ventricular
      hypoplasia, double outlet right ventricle with transposition, left ventricular
      sinusoidal malformation and right ventricular dysplasia. In several cases there
      were additional intracardiac malformations, including ventricular septum defect,
      atrial septum defect as well as different forms of pulmonary stenosis. Seven
      patients had undergone one or more palliative repairs that consisted of modified
      Blalock-Taussig shunts, Glenn's cavopulmonary anastomosis, Waterstone shunt,
      Blalock-Hanlon atrioseptectomy and Brock pulmonary valvotomy. Two patients had
      undergone Senning procedure for transposition of the great arteries. The donor
      cardiectomy was modified in order to include complete inflow and outflow tissue
      in the explant and transplantation could be performed without prosthetic material
      in all patients; deep hypothermic cardiac arrest was never necessary in this
      series. There was no early or late mortality after a mean follow-up of 37 months
      (range 4 to 74 months); postoperative echocardiography and cardiac
      catheterization demonstrated perfect anatomical and functional results in all
      patients. Adolescent and adult patients with complex congenital cardiac diseases
      can be transplanted with a very low perioperative risk, even after several prior
      operative procedures.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7811479
TI  - Failure mode of a new pericardial valve prosthesis (Sorin Pericarbon). A
      morphological study.
AB  - Between February 1986 and February 1992, 144 patients (mean age 69 years)
      received 149 bovine pericardial valve bioprostheses (Sorin Pericarbon). Out of
      this group 10 patients required reoperation because of valvular dysfunction.
      Defect bioprostheses (7 aortic valves, 3 mitral valves), removed 34 to 81 months
      after implantation, were studied by X-ray analysis as well as light and electron
      microscopy. Seven out of ten valves were explanted because of valvular stenosis,
      two valves had to be replaced because of valvular regurgitation and one because
      of paravalvular leakage. X-ray analysis revealed severe clacification of the
      cusps in all cases. Mineralization occurred predominantly next to commissural
      attachment zones. Cuspal tearing, associated with calcific degeneration of the
      tissue, was observed in two cases. Beside the commissures, accelerated tissue
      degeneration could be detected near the basal suture line: disintegration of
      collagen bundles by invading macrophages and mineral deposits was prominent in
      these regions. Scanning electron microscopy revealed the presence of
      circumscribed areas of endothelial-like cell lining on both surfaces of the cusps
      of five explants. Valvular stenosis, caused by severe calcification of
      commissural as well as basal regions of the leaflets, is the principal failure
      mode of the Sorin Pericarbon heart valve prostheses. As an additional aspect, the
      basal suture line must be assumed to be a critical determinant in accelerating
      tissue degeneration. Long-term clinical studies will be required to evaluate the
      clinical performance of this valve, focusing on thromboembolic complications,
      hemodynamic function and long-term durability.

PMID- 7811480
TI  - Calcification of valve bioprostheses: the cardiac surgeon's nightmare.

PMID- 7811481
TI  - Effect of the preservation of annulo-papillary continuity on left ventricular
      ejection fraction after mitral valve replacement. A clinical randomized study on
      patients affected by rheumatic valve disease.
AB  - This perspective study has been designed to evaluate the modifications induced on
      left ventricular contractility by the interruption of annulo-papillary continuity
      during mitral valve replacement in patients with rheumatic valve disease.
      Patients with associated cardiac diseases were not admitted to the study. Sixty
      nine patients entered the trial, each patient was randomly assigned to mitral
      valve replacement either with preservation of the annulo-papillary continuity
      (PAPC) or with excision of all the chordae (EC). Patients with mitral stenosis
      (MS) and combined mitral disease (MS & R) were considered separately. The four
      groups were similar regarding preoperative characteristics including the
      radioisotopic left ventricular ejection fraction (LVEF). All the patients had the
      mitral valve replaced with a bileaflet prosthesis fixed by interrupted mattress
      sutures in the supra-annular position; the methods of anesthesia, cardiopulmonary
      bypass and myocardial preservation were similar in all patients. In the patients
      of the two EC groups a complete excision of the mitral valve was performed. In
      the patients of the PAPC groups a modified Miki's technique was used to preserve
      annulo-papillary continuity; in eight cases with heavy calcification of the
      subvalvular apparatus, after total excision of the mitral valve, PTFE sutures
      were used to reconnect the annulus to the papillary muscles. After 6 months'
      follow-up, 2D and Doppler echocardiography was completed in each patient to
      confirm the absence of any prosthetic leakage and left ventricular outflow tract
      obstruction. (LVOT).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7811482
TI  - Comparison of epidural analgesia and cryoanalgesia in thoracic surgery.
AB  - A prospective study was carried out in 120 patients undergoing elective
      thoracotomy for parenchymal disease. Patients were randomized into three groups:
      A (control group), B (epidural analgesia), C (freezing of intercostal nerves).
      Subjective pain relief was assessed on a linear visual analog scale. Analgesic
      requirements were evaluated during the 12 days following surgery, or until
      discharge if earlier. The vital capacity (VC) and forced expiratory volume in 1 s
      (FEV1) were measured on the day before operation and on the 1st, 2nd, 3rd and 7th
      postoperative days (POD). Subjective pain relief was significantly better in
      Group B in comparison with Group A (P < 0.05) or C (P < 0.05). Group C had the
      lowest score on the 11th and 12th POD but differences were not statistically
      significant. Requirements for intravenous analgesics were lower in Group B than
      in the control group (P < 0.05) during the first 3 POD, and in group C than in
      the control group the day of operation (P < 0.05). Oral analgesic requirements,
      when compared with controls, were lower in group B during the first 5 POD, and
      lower in group C on the 3rd and the 4th POD (P < 0.05). Cryoanalgesia led to a
      slight but not significant increase in VC and FEV1. Epidural analgesia led to a
      significant increase when compared with controls in FEV1 during the first 3 POD,
      and in FVC on the 7th POD (P < 0.05). It is concluded that epidural analgesia led
      to the best pain relief and restoration of pulmonary function after
      thoracotomy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7811483
TI  - Pericardectomy for chronic constrictive pericarditis: risks and outcome.
AB  - From 1970 to 1990, 71 consecutive patients (51 men and 20 women) had
      pericardectomy for chronic constrictive pericarditis. The mean age was 44.2 +/-
      16.1 years. In the preoperative state 2.8% were in NYHA class I, 18.3% in II,
      43.6% in III and 35.2% in IV. The operative approach was median sternotomy in 93%
      and left anterolateral thoracotomy in 7%. The early mortality rate (within 30
      days after operation) was 5.6%. All four early deaths were female (P < 0.001), in
      the preoperative state the patients were classified as NYHA class IV (P < 0.01).
      These patients had a significantly higher preoperative mean right atrial pressure
      then survivors (21.5 +/- 8.5 mmHg vs 13.6 +/- 5.6 mmHg, P < 0.005). Follow-up was
      obtained for 65 patients (91.5%) and averaged 11 +/- 5.8 years (the longest
      period was 21.5 years). Actuarial survival at 5, 10, 15 and 20 years for all
      patients was 84.6% +/- 4.5%, 80.1% +/- 5.3%, 70.5% +/- 6.9% and 65.8% +/- 7.9%,
      respectively. In the preoperative state 10 of the 12 late deaths (83%) were
      classified NYHA class IV and the remaining ones class III. Of the 49 patients
      alive 23% belong to NYHA class I, 42% to II and 35% to III; none is in class IV.
      Negative predictors of survival were found to be preoperative NYHA class IV (P <
      0.01), low-voltage electrocardiogram (ECG) (P < 0.01), ascites (P < 0.01),
      dyspnea at rest (P < 0.05) and hyperbilirubinemia (P < 0.05).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7811484
TI  - Influence of systemic hypothermia on systolic and diastolic functional recovery
      after continuous warm antegrade blood cardioplegia.
AB  - Experimental observations in our laboratory indicate that myocardial recovery is
      similar following warm or cold antegrade blood cardioplegia when the core
      temperature is maintained at 37 degrees C. To determine the effects of
      hypothermia on myocardial recovery, 15 adult mongrel dogs were randomized to
      normothermic or hypothermic bypass (28 degrees C) during 60 min of continuous
      warm antegrade blood cardioplegia. The hypothermic group was rewarmed after
      releasing the aortic cross-clamp and bypass was discontinued at 30 min in both
      groups. Myocardial recovery was assessed at 60, 90, and 120 min after the arrest.
      Core temperature was maintained in the normothermic group but gradually decreased
      after bypass in the hypothermic group, reaching a low of 33.8 +/- 1 degrees C at
      120 min. Myocardial functional recovery was preserved after normothermic bypass.
      The decrease in core temperature, however, that was observed after systemic
      hypothermia, was paralleled by significant decreases in the maximum rate of left
      ventricular pressure rise (dp/dt), the maximum elastance of the left ventricle,
      and preload recruitable stroke work. Diastolic function decreased slightly, but
      not significantly, during reperfusion following systemic hypothermia but was
      unaltered after normothermic bypass. Myocardial oxygen consumption was unchanged
      in both groups. Myocardial ultrastructure was preserved after normothermic
      bypass. In contrast, cellular oedema and mild ultrastructural changes were
      evident after systemic hypothermia. We therefore conclude that the use of
      systemic hypothermia during bypass is associated with lower core temperatures
      during early recovery which results in impaired functional recovery.

PMID- 7811485
TI  - Third-time coronary bypass operation. Analysis of selection mechanisms, results
      and long-term follow-up.
AB  - Twenty-six patients underwent a third coronary artery revascularization between
      1984 and 1993 at Hopital de la Tour, Geneva, Switzerland. These patients
      represent 5.4% of coronary artery bypass graft (CABG) reoperations and 0.8% of
      the total CABG operations (3129) during the same time period. There were 23 men
      (85%), the mean age was 57.2 years (range 33-71), 18 patients (69%) had 3-vessel
      disease and the mean left ventricular ejection fraction (LVEF) was 59% (range 32
      83%). The reason for the third operation was graft failure in 62% of the cases.
      Twenty-five patients (96%) were in Canadian Cardiovascular Society (CCS) class 3
      or 4 preoperatively. Direct myocardial revascularization was performed in all
      patients with a mean of 3.2 grafts per patient (range 1-6). Thromboendarterectomy
      was performed in six patients (23%) and patch was used in four (15%). The
      internal mammary artery (IMA) was utilized in 85% of the patients. In-hospital
      mortality was 11.5% (3 patients). Non-fatal perioperative myocardial infarction
      and re-exploration for bleeding did not occur in this group of patients.
      Respiratory failure necessitating prolonged ventilatory support occurred in five
      patients (19.2%). Long-term follow-up was carried out for all 23 hospital
      survivors. The mean follow-up time was 52 months. The 5-year actuarial survival
      rate was 84.5% for the entire group and 95.7% for hospital survivors. The
      preoperative CCS functional class had significantly improved at the end of the
      follow-up, P < 0.001. Our data suggests that a third-time coronary
      revascularization can be justified, with gratifying operative success and good
      long-term clinical results.

PMID- 7811486
TI  - Coronary artery bypass grafting in chronic renal dialysis patients: intensive
      perioperative dialysis and extensive usage of arterial grafts.
AB  - Twenty-three chronic renal dialysis patients underwent coronary artery bypass
      grafting (CABG). Eighteen patients were maintained on hemodialysis and 5 patients
      received continuous ambulatory peritoneal dialysis. Eighteen patients (78%) had
      triple vessel disease or left main disease. The mean number of revascularized
      vessels was 2.2 +/- 0.8, and the graft materials used were left internal thoracic
      artery (21), right internal thoracic artery (7), right gastroepiploic artery (7),
      and saphenous vein (15). The utilization index of arterial grafts (percentage of
      patients with at least one arterial graft) was 95.7%. Intraoperative hemodialysis
      (HD) was performed during cardiopulmonary bypass in all patients. In 17 patients
      on HD preoperatively, peritoneal dialysis (PD) was initiated immediately after
      the operation, and maintained until the hemodynamics stabilized sufficiently to
      resume HD (mean: 5.7 +/- 3.4 days after operation). In the patients with a
      gastroepiploic artery pedicle, PD could be established without leakage of
      dialysis fluid into the pericardial cavity by means of making a smaller hole in
      the diaphragm, passing the skeletonized portion of the graft through the hole and
      sealing the hole using fibrin glue. There were no hospital deaths. Angiography
      revealed an overall graft patency rate of 95.8% (46/48), and all arterial grafts
      were patent. There were 4 late deaths (1 cardiac, 3 cerebral hemorrhage). In
      conclusion, CABG can be accomplished in chronic renal dialysis patients with
      excellent early and long-term results through an intensive perioperative dialysis
      program and extensive usage of arterial grafts.

PMID- 7811487
TI  - Successful surgical management for multiple cerebral mycotic aneurysms involving
      both carotid and vertebrobasilar systems in active infective endocarditis.
AB  - Mycotic aneurysm is usually found in the middle cerebral artery associated with
      infective endocarditis. Previous reports we have identified include only 4 cases
      of vertebrobasilar aneurysm. We report on a 29-year-old female who had multiple
      mycotic aneurysms involving both the carotid and vertebrobasilar systems
      complicated by intracranial hemorrhage with infective endocarditis, in whom
      staged operations, mitral valve replacement and craniotomies, were successfully
      performed.

PMID- 7811488
TI  - [Chronic cluster headache: course and outcome of treatment].
AB  - We analyze the results of treatment and the course of disease in 20 patients
      suffering from chronic cluster headache. Patients were followed for an average of
      5 years. Sumatriptan provided the most effective relief of symptoms in those who
      used that medication. The results of surgical and medical prophylaxes were poor.
      The disease either remitted or changed to an episodic variety after several
      months or years in most patients. There is no evidence to suggest that these
      changes were related to any particular treatment.

PMID- 7811489
TI  - [Congenital muscular dystrophy: report on 10 cases].
AB  - Clinical features in 10 cases (3 males, 7 females) with congenital muscular
      dystrophy (CMD) are reported. Six patients suffered from pure forms of CMD. Two
      patients had diffuse cerebral white matter involvement of both hemispheres,
      demonstrated by computerized tomography and magnetic resonance imaging. Two
      patients were diagnosed as having Walker-Warburg syndrome on the basis of
      clinical and neuroradiological findings. The present series of patients further
      illustrates the heterogeneity of the various entities included under the term CMD
      even when central nervous system involvement is not suspected.

PMID- 7811490
TI  - [Neuropsychological signs in frontal and temporal supratentorial neuroepithelial
      tumors].
AB  - We have studied a group of patients with supratentorial neuroepithelial tumors
      before and after surgical treatment. The main neuropsychological impairments were
      in verbal memory. After surgery, neuropsychological performance improved in
      36.1%, worsened in 13.6% and remained the same in 29.7%. In 21.6%, normal
      performance had already been observed. The physiology of brain tumors make it
      difficult to distinguish between frontal and temporal symptoms. However,
      neuropsychological assessment in useful for maximizing the patient's social
      adjustment.

PMID- 7811491
TI  - [Multicenter register of index cases of dementia. A study by the Spanish
      Neurological Society's dementia group].
AB  - We report the objectives and case registration methods used by neurologists
      belonging to the Spanish Neurological Society's dementia group (GERMICIDE).
      Forerunners of the present project are also described. The group's principal aim,
      which is to determine the distribution of dementia in the "neurological"
      environment is pursued by enrolling consecutive index cases (new presentations)
      arriving at 18 Spanish neurological units over a period of 2 years. A standard
      protocol was used to study the patients and final diagnoses were agreed upon in
      keeping with international criteria for dementia and the main neurological
      diseases (DSM-III-R, CDR and others). A second objective is to study risk factors
      for the main etiological groups of dementia (Alzheimer's disease and vascular
      dementia) and to follow each patient in the cohort until death in order to assess
      the course of disease and its biological markers. The series will be large, as
      there are already over 800 cases listed in the coordinating centre even though
      the period of enrollment has not ended.

PMID- 7811492
TI  - [Spontaneous and reflex motor behavior in brain death].

PMID- 7811494
TI  - [Bilateral hemodynamic infarcts after cardiac surgery].

PMID- 7811493
TI  - [New antiepileptic drugs: vagabatrin, lamotrigine and felbamate].

PMID- 7811495
TI  - [Paroxysmal unilateral hyperhidrosis].
AB  - We report the case of a 35-year-old woman with paroxysmal unilateral
      hyperhidrosis which developed after thoractotomy for Barret's esophagus (benign
      esophageal stenosis). Hyperhidrosis was on the right side of the face and in the
      metameric areas corresponding to the right spinal roots C2, C3 and C4. Paroxysms
      of sweating lasting from 15 to 30 min occurred several times daily, either
      spontaneously or related with acid food ingestion. The symptoms have been present
      for the last 10 years. Paroxysmal unilateral hyperhidrosis is a rare disorder of
      the autonomic nervous system. It has been reported in association with peripheral
      nerve, spinal cord and cerebral lesions, and in some cases the etiology is
      unknown.

PMID- 7811496
TI  - [Idiopathic granulomatous angiitis of the central nervous system].
AB  - We diagnosed idiopathic granulomatous angiitis of the central nervous system in a
      51-year-old man by leptomeningeal and cortical biopsy. The patient's disease was
      prolonged, with symptoms recurring over a period of 15 years. Treatment with
      prednisone and cyclophosphamide produced total remission after a follow-up of 22
      months. Computerized tomography was less sensitive and revealed fewer lesions
      than did magnetic resonance imaging. Angiography was not sensitive and
      leptomeningeal and cortical biopsy were essential for diagnosis in this patient.

PMID- 7811497
TI  - [Reversible changes in magnetic resonance images in two cases of complex partial
      status epilepticus].
AB  - Magnetic resonance imaging (MR) is the imaging method of choice for studying
      epilepsy, particularly when the focus is in the temporal lobe. MR is useful for
      diagnosing many pathological anomalies in this site; nevertheless, transient
      alterations that can mimic structural lesions are sometimes observed. We describe
      2 patients in complex partial status epilepticus with MR alterations in the
      temporal lobe signals, on the left in one case and on the right in the other.
      After symptoms subsided and electroencephalographic alterations disappeared, new
      MR showed the disappearance of the changes in both patients. Transient changes of
      MR in epileptic patients may be a product of local blood flow disruption of the
      hematoencephalic barrier or local edema during seizure. Awareness of such
      transient changes can reduce the number of unnecessary diagnostic procedures
      and/or aggressive treatments.

PMID- 7811498
TI  - [Axillary skin biopsy: a reliable diagnostic test for Lafora's disease].

PMID- 7811499
TI  - [Pathological startle reflex secondary to hypoxemia].

PMID- 7811500
TI  - [Insomnia secondary to vascular pontine tegmental lesions: role of the superior
      central raphe nucleus].

PMID- 7811501
TI  - [Laryngeal reinnervation: transposition of neuromuscular pedicles].
AB  - Following Tucker's technique, a muscle-nerve pedicle implantation in the
      denervated posterior cricoarytenoid muscle was performed in five dogs. Results
      were evaluated after six months by videolaryngoscopy, evoked muscle action
      potentials and histomorphometric studies. Partial motion recovery of the
      reinnervated side was observed endoscopically in three dogs. Histomorphometric
      evaluation showed evidence of muscle reinnervation in all of the five dogs.
      However, no muscle action potentials were obtained in the posterior
      cricoarytenoid muscles after stimulation of the ansa hypoglossi branch. These
      data suggest that the ansa hypoglossi neuromuscular pedicle does not result in
      reinnervation, and that reinnervation of the posterior cricoarytenoid muscle may
      occur via other neuromuscular pathways.

PMID- 7811502
TI  - [Revision of stapedectomy (110 ears)].
AB  - We have carried out a retrospective study of 110 ears in patients affected with
      otosclerosis who underwent revision of stapedectomy, from 1979 to 1991, because
      they did not achieve hearing improvement or still presented persistent dizziness
      after primary stapedectomy. In our series, the most common causes of surgical
      failure after the first surgery are: displacement of the prosthesis (36.3%),
      ossicular chain alterations (21.8%) and regrowth of otosclerotic bone in the oval
      window (19.9%). One year after surgery, hearing test was compared with
      preoperatory tonal audiometry, finding and improvement in 48.1% (closure of 20 dB
      HL or more of the air-bone GAP), no changes in 43.6% and deterioration of the
      audition in 8.1%. Finally, we give some advises to prevent hearing loss in the
      revision of stapedectomy.

PMID- 7811503
TI  - [Chondro-perichondrial connections in otic surgery (CPC)].
AB  - Tympanoplasty does not resolve problems such as tympanic reconstruction,
      pneumatic cavity and ossicular transmission mechanism. With the purpose to solve
      these problems, we used autografts of tragal cartilage with its perichondrial
      membrane. In just one surgical procedure, we built a transmission mechanism and a
      consistent new tympanic membrane. Results obtained after 2 years of experience
      are very encouraging, since postoperative auditive function improves up to 75%;
      also, a good pneumatic cavity and a well vascularized new tympanic membrane are
      achieved. Reabsorption of the cartilage was not seen in any case.

PMID- 7811504
TI  - [Our experience with reconstructive surgery++ of the middle ear in
      tympanoplasties with mastoidectomy].
AB  - In our department, we studied 243 patients who underwent open or close
      tympanoplasty, from 1984 to 1989, generally caused by cholesteatoma (229 cases)
      or by non-cholesteatomatous chronic suppurative otitis media (14 cases).
      Extrusion of the prosthesis occurred in 15 (11.11%) of a total of 136 cases after
      an average time of 12.46 months during a 4 to 8 years evolution period. From
      these cases 5 out of 59 were made with plastipore Porp (8.47%) and 10 out of 76
      with plastipore Torp (13.15%). autologous ossicles did not extrude in any case.
      In the cases of cholesteatoma, open (62.7%) and close (37.3%) techniques were
      performed, and after above mentioned period of evolution, recidivism of
      cholesteatoma occurred in 4.11% of patients.

PMID- 7811505
TI  - [Assessment of vertebrobasilar insufficiency using magnetic resonance
      angiography].
AB  - We present the protocol for diagnosis of VBI followed by ENT and Radiology
      Departments of the Valencia University General Hospital, using the 2D-PC magnetic
      resonance angiography technique (MRA) with variable VENC (30 and 40 cm/s) with a
      SIGMA 1.5 T Advantage system version 5 x with the corresponding software review
      5.2 (General Electric Medical Systems, Milwaukee, WI, USA). After a coronal
      angiographic projection is obtained in a neutral position on an axial plane of
      localization, the patient head is set at the maximum left and right rotation and
      hyperextension allowed by patient and system. In this way, a coronal angiographic
      sequence is obtained in order to visualize potential compressions, decreases of
      the flow, arterial loops, etc. MRA is a non-invasive technique that requires no
      contrast, does not expose the patient to ionizing radiation, and allows to change
      the position of the patient's head easily. Since no hospitalization is required
      and contraindications are minimal (e.g., implanted pacemakers...), we believe
      that MRA constitutes and ideal screening technique to assess the vertebro basilar
      system. The results obtained and the advantages provided by MRA over Doppler
      ultrasound and X-ray angiography are showed.

PMID- 7811506
TI  - [Cerebral SPET in vertigo syndrome].
AB  - Diagnosis of vertigo in the absence of permanent tissue damage is still
      difficult. Since a functional deficit should be associated with a reduction in
      the blood perfusion, authors performed a cerebral SPET in 23 patients with
      central vertigo, 10 with peripheral vertigo and 17 normal controls, and compared
      the results with those obtained by CT, NMR and doppler investigation. Cerebral
      SPET showed higher specificity and sensitivity than other techniques employed in
      the investigation of peripheral vertigo. These results demonstrated the
      usefulness of cerebral SPET in the diagnosis of vertigo, particularly in cases of
      vascular origin. Furthermore, this technique may be performed in any pathology
      where tissue damage is associated with a perfusion deficit detectable by SPET
      investigation.

PMID- 7811507
TI  - [Image analysis of naso-sinusal pathology with computerized tomography].
AB  - Imaging analysis has been applied to study typical cases of nasosinusal diseases,
      in an attempt to determine its capabilities for CT scan interpretations. Thus,
      polyps with sinusitis, cerebrospinal fluid occupying sinuses, cysts and bone
      tumors may be compared in order to obtain objective results that may help in the
      differential diagnosis in these conditions.

PMID- 7811508
TI  - [Endoscopic approach of antrochoanal polyps].
AB  - Antrochoanal polyps represent a particular pathology among nasosinusal polyposis.
      Since KILLIAN'S first report in 1906, several pathogenic mechanisms and surgical
      techniques have been described. Surgical removal of an antrochoanal polyp by the
      classic Caldwell-Luc approach has been reviewed since the beginning of the use of
      nasosinusal functional endoscopic surgery. We present 12 cases of antrochoanal
      polyps removed by this technique in our hospital, during the last three years,
      analyzing the results and complications of this endoscopic approach. We conclude
      that functional endoscopic surgery of the sinus for removal of antrochoanal
      polyps, is a recommendable surgical technique due to its efficiency and low
      morbidity.

PMID- 7811509
TI  - [Postoperative pain in tonsillectomy in general anesthesia and local
      infiltration].
AB  - The aim of this study is to demonstrate that blockade by bupivacaine of
      nociceptors located at the same level than the anterior tonsillar pillar, can
      reduce the pain in the postoperative period following tonsillectomy, thus, making
      easier the recovery of these patients at home. For this purpose, fifty children
      aged 2 to 13 years old, are studied. A double blind study is performed
      distributing the children randomly in two groups. One group is infiltrated prior
      to surgery with 1 cm3 of bupivacaine 0.25% + epinephrine 1:200,000 in three
      points of the anterior tonsillar pilla, while the other group is infiltrated with
      normal saline. The pain in the immediate postoperative period (60 minutes) is
      classified in five categories by a visual pain scale (scored 1-10). Short term
      postoperative (7 days) is also classified in five categories by a scale (scored 1
      10) based in the information provided by the mother. Statistical analyses of the
      data is performed considering the statistical significance of the correlations
      obtained from the Chi2 and Student's tests. CONCLUSION: pre-incisional
      infiltration in the anterior tonsillar pillar with bupivacaine in the
      tonsillectomy will cause a remarkable reduction in the intensity of the
      postoperative pain.

PMID- 7811510
TI  - [Laryngeal tuberculosis: report of 10 cases].
AB  - The aim of this paper is to present a retrospective study on laryngeal
      tuberculosis cases presented at our Department from 1982 to 1993. In addition to
      usual techniques for tuberculosis diagnosis (cultures, Mantoux test and chest X
      rays), biopsies for histological sections were carried out. Epidemiological,
      clinical diagnosis and treatment aspects are presented; the higher male incidence
      and the common suspicion of laryngeal carcinoma are emphasized. When we compare
      our results with those of several reports, we confirm the increase in the number
      of cases diagnosed in the last three years of the study. We emphasize the
      importance of histopathological diagnosis to rule out a neoplasm.

PMID- 7811511
TI  - [Dural arteriovenous fistula of the lateral sinus: origin of objective tinnitus].
AB  - Objective tinnitus usually has a vascular origin, but dural arteriovenous
      fistulas are rarely the cause of this sign. We report a case of arteriovenous
      meningeal fistula (AVMF) of the lateral sinus, origin of pulsatile objective
      tinnitus. Etiology, pathophysiology, symptoms, diagnosis, differential diagnosis
      and treatment of these fistulas are reviewed.

PMID- 7811512
TI  - [Amelanotic mucous melanoma of the nasal cavity. Report of a case].
AB  - We report a case of mucosal melanoma of the nasal cavity, of amelanotic nature,
      in a fifty five years old white man. Clinical course started with nasal
      obstruction and bloodstained rhinorrhea. We want to emphasize the extreme
      uncommonness of this type of tumor, its bad prognosis, and its difficult
      diagnosis. The treatment offers long term remission to a limited number of
      patients. For all these reasons, we have carried out a literature search on this
      topic and this paper shows the results.

PMID- 7811513
TI  - [Hemifacial malignant granuloma as clinical manifestation of peripheral T-cell
      lymphoma].
AB  - The present clinical and pathological study describes the cases of two patients
      having infiltrate and ulcerous lesions of the nose, hard palate and rhinopharynx
      clinically consistent with a malignant midline granuloma. Histologically,
      infiltrates presented atypical lymphoid cells around small vessels and damage of
      the vascular wall. Immunohistologic study, using monoclonal antibodies on both
      fresh and paraffin embedded tissues, led to the positive diagnosis of peripheral
      lymphoma of T cells.

PMID- 7811514
TI  - [Hypernephroma metastasis in frontal sinus].
AB  - PURPOSE: We present a case of metastatic neoplasia in the right frontal sinus
      derived from and hypernephroma, with a clinical picture that initially was
      interpreted as a mucocele. PATIENTS AND METHODS: Sixty years old male. Personal
      history: prostatectomy and left nephrectomy because of hypernephroma three years
      before. In december 92 the patient reported a protrusion in the right frontal
      sinus. CT scans and NMR revealed a breakage of the external and internal walls of
      the right frontal sinus and the right orbital roof. In february 93 a surgical
      exploration of the frontal sinus revealed the metastatic nature of the lesion.
      DISCUSSION: Metastatic tumors in paranasal sinuses are infrequent since most of
      the tumors in this localization are primary. Metastatic affectation of the
      frontal sinus is extremely rare. We recommend the systematic exploration of
      paranasal sinuses in patients affected by hypernephroma.

PMID- 7811515
TI  - [Acute respiratory obstruction caused by laryngeal rheumatoid arthritis].
AB  - We present a case of acute upper airway obstruction due to cricoarytenoid
      arthritis in severe rheumatoid arthritis. Although laryngeal involvement is
      common in severe rheumatoid arthritis, the upper airway obstruction is a very
      rare complication. The endotracheal intubation may be very difficult in these
      patients, thus fiberotopic bronchoscopy may be useful. Surgery is the final
      treatment.

PMID- 7811516
TI  - [Laryngeal fibrosarcoma. Report of 2 new cases].
AB  - Sarcomas constitute less than one percent of laryngeal neoplasms. Fibrosarcomas
      are by far the most commonly reported mesenchymal tumors of the larynx. We report
      two cases of fibrosarcoma of the larynx and discuss clinical aspects, diagnosis
      and treatment.

PMID- 7811517
TI  - [Mixed tumor in cervical salivary heterotopy].
AB  - This paper presents a case, infrequent and clinically unsuspected, of pleomorphic
      adenoma in the upper region of the neck in front of the sternocleidomastoid,
      independent of the salivary glands. The tumor developed within an heterotopic
      salivary gland of seromucose type, the histopathologic study of the surgical
      piece being decisive in the diagnosis. The characteristics of salivary
      heterotopias of the neck, and their diagnostic difficulties and histogenetic
      problems are reviewed.

PMID- 7811518
TI  - [Fibrosarcoma of the neck: report of a new case].
AB  - We present a case of a 57 years old male diagnosed of neck fibrosarcoma. The main
      characteristics in this type of tumors, the importance of performing CT scan and
      histopathological studies in the diagnosis and treatment are emphasized. We
      conclude that this disease, though rare, must be taken into consideration in
      order to achieve a better prognosis in these patients.

PMID- 7811519
TI  - Diffuse liver disease.

PMID- 7811520
TI  - Upper gastrointestinal tract.

PMID- 7811521
TI  - Pancreas and ampulla of Vater.

PMID- 7811522
TI  - Rectum.

PMID- 7811523
TI  - Endoluminal ultrasound in gastroenterology: application of new technology.

PMID- 7811524
TI  - Pediatric gastrointestinal tract.

PMID- 7811525
TI  - Gastrointestinal ultrasound.

PMID- 7811526
TI  - Acute appendicitis.

PMID- 7811527
TI  - Liver transplantation.

PMID- 7811528
TI  - Comparison of autopsy, clinical and death certificate diagnosis with particular
      reference to lung cancer. A review of the published data.
AB  - Some clinicians and some epidemiologists appear to be under the illusion that
      techniques available for the diagnosis of internal diseases such as lung cancer
      have improved so much that autopsies are not necessary on the bodies of most
      people who die. Partly for this reason, partly for economic reasons and partly
      because clinicians fear litigation if autopsy shows that they treated patients
      for the wrong disease, autopsy rates have been falling in most developed
      countries. The object of the present review was to ascertain how much reliance
      can reasonably be put on clinical diagnoses made and death certificates completed
      in the absence of autopsy data. In the case of lung cancer, high rates of false
      positive and false negative diagnoses are universally prevalent, with biases
      influencing these rates, so that smokers are more likely to be appropriately
      investigated for lung cancer, and false negatives are commoner in non-smokers.
      All investigators who have compared clinical-based and autopsy-based death
      certificates have concluded that higher autopsy rates are necessary and the
      results of one study suggest that a high autopsy rate in a hospital leads to
      improvements in the accuracy of clinical diagnoses. The extent to which diagnoses
      on death certificates that are dependent solely on clinical data are seriously
      inaccurate for internal diseases such as lung cancer should engender caution in
      all who use mortality data to guide public health policies and to identify and
      quantify environmental risks to healths.

PMID- 7811529
TI  - Polyagglutinable Pseudomonas aeruginosa from cystic fibrosis patients. A survey.
AB  - Chronic Pseudomonas aeruginosa lung infection is responsible for most of the
      mortallity and morbility observed in cystic fibrosis patients. During the course
      of the disease, the bacteria change from being O-serogroup typable
      (monoagglutinable), non-mucoid, resistant to normal human serum and motile, to
      become O-serogroup non-typable (polyagglutinable), serum-sensitive and non
      motile. In spite of high levels of antibodies produced by the patient, and
      intensive antibiotic therapy it is not possible to eradiate the polyagglutinable
      bacteria from the lungs of the patients. The bacteria will reappear and it is not
      fully understood if it is the same strain which reappears, or it is a super
      infection with a new strain which takes place. A reliable and stable typing
      method is needed to clarify this question. In the present study, the conventional
      typing methods, such as serotyping, phage typing and pyocin typing were compared
      with the newer DNA typing methods, such as, restriction fragment length
      polymorphism (RFLP) in combination with pulsed field gel electrophoresis (PFGE)
      and typing with a specific DNA probe. Typability, reproducibility and
      discriminatory power using the different typing methods were investigated. The
      conventional typing methods have proved to be adequate when typing P. aeruginosa
      isolates from non cystic fibrosis sources, but because the majority of cystic
      fibrosis P. aeruginosa isolates are polyagglutinable or non typable, serotyping
      is not useful. Phage typing also lacks discriminatory power as it lumps up to 40%
      of the isolates in the same phage group. Pyocin typing has the disadvantage of
      low reproducibility. Most of the conventional typing methods are based on
      receptors on the bacterial surface, which on exposure to the environmental
      conditions in the lung, are likely to provoke phenotypic changes of the bacteria.
      The obvious advantage of the newer DNA typing methods is that these methods are
      based on internal properties of the bacteria, as part of the bacterial genome is
      investigated. The present study has revealed that for the time being, restriction
      fragment length polymorphism (RFLP) and pulsed field gel electrophoresis (PFGE)
      in combination with phage typing is the best method of typing P. aeruginosa
      isolates from cystic fibrosis patients for epidemiological purposes.

PMID- 7811530
TI  - Acinetobacter: epidemiological and taxonomic aspects.

PMID- 7811531
TI  - Cellular distribution of HIV type 1 Nef protein: identification of domains in Nef
      required for association with membrane and detergent-insoluble cellular matrix.
AB  - Cellular distribution of HIV-1 Nef protein was studied by expressing the protein
      in mammalian cells. Cell extracts were fractionated by low- and high-speed
      centrifugation and by nonionic detergents. Two Nef-related proteins were
      expressed in COS cells, Nef-27kD and Nef-25kD. Nef-27kD, an N-myristoylated form
      of Nef, was found in the cytosol and in association with a particulate fraction
      of the cytoplasm. Treatment of the particulate cytoplasmic fraction with nonionic
      detergents, using three different protocols designed to isolate the cytoskeleton
      matrix, indicated that part of Nef was sensitive and part was resistant to
      detergent solubilization. These two cellular fractions represent membrane- and
      cytoskeleton-associated Nef. Nef-25kD, initiated from an in-frame AUG codon, was
      not modified with myristic acid at the amino terminus. Consequently, this protein
      was present in a soluble form in the cytosol. Furthermore, a mutant of Nef-27kD,
      in which the myristoylation signal is deleted, appears as a cytoplasmic soluble
      protein. To determine domains in Nef that are responsible for its subcellular
      distribution, successive internal deletions of 14-20 amino acids were introduced
      at the N-terminal portion of the protein. Five mutants were evaluated with
      respect to their cellular localization. One mutant (pSVLA-5), from which amino
      acids 73-88 were deleted, did not copurify with the detergent-insoluble fraction.
      The protein was, however, present in the particulate cytoplasmic fraction,
      presumably in association with membranes. Taken together, these results suggest
      that N-myristoylation of Nef affects its association with both membranes and
      cytoskeleton.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7811532
TI  - Immunogenicity of Nef protein of SIVSMM-PBj14 expressed in a live vaccine strain
      of Salmonella species.
AB  - The nef gene of an infectious molecular clone of SIVSMM isolate PBj14 was fused
      to the glutathione S-transferase gene of Schistosoma japonicum to generate
      plasmid pEMC100. The recombinant plasmid was placed in an aroA live vaccine
      Salmonella dublin strain, and the production of GST-Nef protein was induced by
      exposure to IPTG. The fusion protein was purified and administered as vaccine to
      BALB/c mice by i.p. injection. Several doses of the purified fusion protein
      produced an earlier anti-GST-Nef response, without an anti-GST response, than did
      IPTG-induced Salmonella live vaccine containing an equal amount (0.1 microgram)
      of fusion protein, apparently because of the transient immunosuppressive effect
      of live vaccine given by injection. The highest anti-GST-Nef titers were obtained
      by a third immunization schedule in which mice were treated with a priming
      inoculum of induced live vaccine followed, after the predicted immunosuppressed
      interval, by two i.p. doses of 1 microgram of purified GST-Nef protein with Ribi
      adjuvant. The data presented here demonstrate that SL5928 aroA, an attenuated S.
      dublin strain, can be used as a live vaccine carrier to express Nef protein of
      SIVSMM-PBj14, one of the most acutely pathogenic primate lentiviruses so far
      described.

PMID- 7811533
TI  - Persistent infection with SIVmac chimeric virus having tat, rev, vpu, env and nef
      of HIV type 1 in macaque monkeys.
AB  - A chimeric human and simian immunodeficiency virus carrying the tat, rev, vpu,
      env, and nef genes of human immunodeficiency virus type 1 was generated. The
      chimeric virus, NM-3n, grew competently in peripheral blood mononuclear cells
      from cynomolgus monkeys like the parental SIVmac. Two cynomolgus monkeys and one
      rhesus monkey inoculated with NM-3n raised antibodies to SIVmac Gag and HIV-1
      Env. The antibodies raised in the cynomolgus monkeys persisted for at least 1.7
      years. The antibodies contained virus neutralizing activity not only to the
      original chimeric virus but also to the parental HIV-1. Infectious viruses were
      isolated from one of the cynomolgus monkeys 37 and 63 weeks after inoculation and
      from the rhesus monkey continuously from 6 weeks after infection onward. The
      recovered virus maintained its chimeric structure but included several clones
      with mutations in the env V3 region. When the recovered virus was inoculated to
      another rhesus monkey, no difference in the frequency of virus recovery was seen
      from the originally infected monkeys. These carrier monkeys have so far shown no
      sign of the disease.

PMID- 7811534
TI  - HIV type 2 proviral load measured by quantitative polymerase chain reaction
      correlates with CD4+ lymphopenia in HIV type 2-infected individuals.
AB  - The efficiency of detection of 2 sets of primer pairs from putatively conserved
      regions of the human immunodeficiency virus type 2 (HIV-2) genome were assessed
      in 86 seropositive individuals from The Gambia by nested polymerase chain
      reaction (PCR). HIV-2 long terminal repeat (LTR) target sequences were detected
      in DNA extracted from peripheral blood mononuclear cells (PBMCs) in 84 of 86
      (97%) individuals whereas HIV-2 integrase (pol) gene sequences were detected in
      39 of 41 (95%) individuals. The use of LTR target sequences and recombinant Pfu
      DNA polymerase, rather than Taq polymerase, in a modified secondary amplification
      reaction mediated the incorporation of 35S-labeled nucleotides in a quantitative
      radiometric assay. This sensitive assay was used to quantify HIV-2 proviral DNA
      in clinical samples and compared well with estimations by limiting end-point
      dilution of target molecules. A linear response between counts and the number of
      copies amplified from serial dilutions of pROD10 plasmid DNA (3-2000 copies)
      yielded a standard curve to allow extrapolation to clinical data. Increased
      levels of HIV-2 proviral DNA, expressed as copies per 10(5) CD4-positive
      lymphocytes, were associated with declining CD4 count in 63 adult patients
      (Spearman rank correlation, r = -0.71, n = 63, p < 0.001) and with the occurrence
      of HIV-related clinical disease. Kruskall-Wallis analysis of variance analysis
      showed the mean proviral copy number (log10) to be significantly different
      between groups (p < 0.001) where CD4 counts were grouped as < 200/mm3 (3.4 +/-
      1.05 copies), 200-500/mm3 (2.84 +/- 0.93 copies), and > 500/mm3 (1.88 +/- 0.43
      copies).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7811535
TI  - Presence in India of HIV type 1 similar to North American strains.

PMID- 7811536
TI  - p17gag sequence of HIV-1GER, a new, highly replicative and highly cytopathic HIV
      type 1 strain of D genotype.

PMID- 7811537
TI  - Keynote address: variations in the natural history of HIV infection.
AB  - In general, the natural history of HIV infection as revealed by prospective
      cohort studies such as the Multicenter AIDS Cohort Study (MACS) is consistent
      with our current understanding of the immunopathogenesis of HIV disease. Although
      the limitations of CD4+ T cell counts as a predictor of response to therapy are
      now recognized, enumeration of these cells remains an important predictor of
      outcome. Additional information regarding prognosis can be obtained using other
      immunological and virological information. Analysis of data from cohort studies
      has revealed varying patterns of CD4+ lymphocyte count decline associated with
      differing evidence of immune activation, specific antibody responses, CD8+ T cell
      responses, and level of viral burden. Of interest, some asymptomatic HIV-infected
      persons appear to show immune stability in the absence of therapeutic
      interventions. In addition, the combination of antiretroviral therapy and
      prophylaxis for Pneumocystis carinii pneumonia (but apparently not prophylaxis
      for fungal or Mycobacterium avium-intracellulare infections) has prolonged
      survival in patients with AIDS.

PMID- 7811538
TI  - Evolving understanding of the immunopathogenesis of HIV.
AB  - Understanding of the immunopathogenesis of HIV infection is becoming more
      advanced as the activity of HIV infection in lymph nodes is appreciated and as
      improved virological measures permit more accurate quantitation of viral burden
      in patients at all stages of HIV disease. Although CD4+ cell counts remain
      important prognostic indicators, their role as a surrogate for direct antiviral
      activity has been questioned and increasing focus has been placed on more direct
      quantitative viral measures that are now available. After an initial explosive
      burst of viral replication during acute seroconversion that is downregulated by
      the immune system, these newer markers have revealed that viral replication is
      ongoing during the so-called "clinically latent" period of HIV infection. One of
      the most active sites of viral replication during this asymptomatic period is in
      lymphoid tissues. Over time, however, immunological control of HIV wanes, the
      site of replication shifts from the lymph nodes to other lymphoid organs, and
      disease progression ensues. The role of viral diversity in late-stage HIV disease
      is now well established, yet its role in pathogenesis and establishment of
      viruses resistant to antiviral agents is not fully established. Increased
      understanding of how HIV causes immune dysfunction may help us control direct and
      indirect (opportunistic) complications of HIV infection.

PMID- 7811539
TI  - Early intervention in HIV infection: where are we?
AB  - Data about the virology and pathogenesis of HIV disease suggest that early
      therapeutic intervention, perhaps even before the CD4+ cell count has fallen
      substantially, would be a theoretically sound approach. A limited number of large
      clinical studies address early therapy with zidovudine. A European-Australian
      study, which enrolled patients with CD4+ cell counts > 400 cells/microliters,
      found a benefit of zidovudine therapy compared to placebo in delaying minor HIV
      manifestations and CD4+ cell loss after a 2-year follow-up period. The results of
      the Concorde study, which enrolled > 1700 asymptomatic patients and followed them
      for an average of 3 years, have created controversy about the results of ACTG
      protocol 019, which had led to widespread zidovudine use for patients with CD4+
      cells < 500/microliters. Although there was a favorable change in CD4+ cell count
      in the Concorde study patients assigned to immediate zidovudine treatment
      compared with those assigned to deferred treatment, there were no significant
      differences in progression to AIDS or survival. Preliminary results from follow
      up of ACTG 019 patients enrolled with CD4+ cell counts of 300-500/microliters
      suggest that the duration of benefit of zidovudine may be longer than in patients
      with CD4+ cell counts less than 300 cells/microliters. Finally, the impact of
      antiretroviral therapy on quality-of-life measures is now recognized as an
      important issue and should be incorporated into treatment decisions. The
      available data from several large studies of patients with asymptomatic HIV
      infection are concordant, in that they suggest that zidovudine has a limited
      duration of efficacy but does not prolong survival.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7811540
TI  - Resistance, drug failure, and disease progression.
AB  - The clinical significance of the reduced in vitro susceptibility of HIV to
      antiretroviral agents has been difficult to elucidate for nucleoside analogs such
      as zidovudine. However, the virological significance of resistance to nevirapine
      and other HIV-1-specific reverse transcriptase inhibitors has been established.
      With antiretroviral therapy, disease progression is not equivalent to drug
      failure, which is not equivalent to drug resistance. Clinical disease progression
      is only indirectly linked to HIV replication. Drug resistance is complex, and
      combining drugs does not appear to delay emergence of resistant strains of HIV
      although it may affect the specific amino acid substitutions. Drug resistance
      does appear to contribute to drug failure. The clinical trial ACTG 116B/117 found
      that the duration of prior zidovudine therapy was not related to the relative
      benefit of switching to didanosine. Preliminary results of analysis of resistant
      strains of HIV isolated from ACTG 116B/117 patients revealed that the relative
      hazard of progression was about threefold higher for patients with high-level
      resistance to zidovudine, syncytium-inducing biological phenotype, and an AIDS
      diagnosis at baseline. This study showed clearly that acquisition of an HIV
      strain with high-level resistance to zidovudine was a poor prognostic factor.
      Although nevirapine resistance emerges rapidly, preliminary data suggest that
      high dosages may be active against HIV even in the presence of resistant HIV
      strains. At the present time, viral resistance and biological phenotype are not
      useful in the management of individual patients.

PMID- 7811541
TI  - Combination therapy: more effective control of HIV type 1?
AB  - The rationale for combining anti-HIV-1 agents is to provide more complete viral
      suppression, to limit the emergence of drug resistance during chronic viral
      replication, and to provide more effective antiretroviral treatment even when
      mixtures of drug-resistant and drug-sensitive strains are present. In vitro
      experiments reveal increased suppression with multiple-drug therapy, but viral
      breakthrough occurs after prolonged time in culture even during triple-drug
      therapy. Clinical results available to date indicate that drugs should be given
      simultaneously for optimal benefit. There appears to be a rationale for early
      initiation of combination therapy before the onset of increased viral burden and
      the emergence of syncytium-inducing viral variants. The results of ACTG protocol
      155 revealed benefit of zidovudine and zalcitabine over monotherapy with either
      agent in patients with CD4+ cell counts > or = 150 cells/mm3. However, further
      clinical studies will be necessary before firm recommendations can be made about
      the indications for combination antiretroviral therapy in HIV-1-infected
      individuals at different stages of disease. Ultimately, we need better drugs, in
      combination, which significantly impact on HIV-1 burden to achieve more complete
      viral suppression and to reduce selection of drug-resistant viral variants.

PMID- 7811542
TI  - Disseminated Mycobacterium avium complex disease in patients with AIDS.
AB  - Disseminated Mycobacterium avium complex (MAC) infection is a common complication
      of advanced HIV disease that is associated with significant morbidity. After
      diagnosis of MAC by recovery of organisms from blood or other normally sterile
      sites, specific treatment with multiple-drug regimens is appropriate and may
      reduce morbidity. Multiple-drug regimens with agents active against MAC should be
      employed to reduce the development of drug resistance. Unfortunately, as most
      clinical trials of anti-MAC agents have lasted 12 weeks or less and have not
      compared specific agents, the most effective multiple-drug regimen has not been
      established. The U.S. Public Health Service Task Force on Prophylaxis and Therapy
      of MAC recommends treatment of disseminated disease with at least two
      antimycobacterial agents, one of which should be clarithromycin or possibly
      azithromycin. Ethambutol, which may have an additive or synergistic effect in
      combination with other anti-MAC agents, is a reasonable second drug. Other agents
      with activity include rifampin or rifabutin, clofazimine, ciprofloxacin, or
      parenteral amikacin. A microbiological response may require up to 2 to 8 weeks.
      The clinical response generally parallels the microbiological response.
      Rifabutin, which is licensed for prophylaxis of MAC, reduces the incidence of and
      delays the time to MAC bacteremia. Individuals at highest risk of MAC bacteremia
      (i.e., CD4+ cell counts of < 75-100 cells/microliters) had the most benefit from
      rifabutin prophylaxis. Tuberculosis must be ruled out before rifabutin
      prophylaxis is initiated. Careful observation without prophylaxis is an
      acceptable alternative for those who are not able to take rifabutin or
      alternative agents.

PMID- 7811543
TI  - Current management of cytomegalovirus disease in patients with AIDS.
AB  - Cytomegalovirus (CMV) infection is common in both homosexual and heterosexual HIV
      infected patients, and causes disease in a substantial proportion of patients
      with AIDS and very low CD4+ cell counts. Both ganciclovir, an analog of the
      nucleoside guanosine, and foscarnet, an analog of pyrophosphate, are licensed for
      treatment of CMV retinitis. They may also have a role in the treatment of
      gastrointestinal disease caused by CMV. In the Studies of Ocular Complications of
      AIDS comparative trial the two agents were equally effective against CMV
      retinitis, but patients receiving foscarnet had significantly longer survival,
      even after adjusting for covariates including antiretroviral therapy. Ongoing
      studies are evaluating higher dosages of foscarnet for maintenance therapy and
      combined therapy with ganciclovir and foscarnet. Tolerance of ganciclovir therapy
      has been facilitated by adjunctive therapy with colony-stimulating factors.
      Because both ganciclovir and foscarnet must be administered by intravenous
      infusion and are associated with significant toxicities, other anti-CMV agents
      are under active development, including HPMPC and an oral formulation of
      ganciclovir. Management of CMV retinitis involves individualizing therapy,
      balancing side effects and administration requirements, and, in many clinical
      settings, the overall cost of treatment.

PMID- 7811544
TI  - Resistant candidiasis.
AB  - Mucosal (oropharyngeal, esophageal, and, in women, vaginal) candidiasis is a
      common infectious complication in HIV-infected patients. There is a wide range of
      drugs to treat or suppress Candida infections. However, with the increasingly
      common use of fluconazole as treatment or prophylaxis in patients with relatively
      advanced HIV disease, mucosal candidiasis that is clinically resistant to
      fluconazole is increasingly recognized. Susceptibility testing for fluconazole
      has not been well standardized, and laboratory and clinical correlations often
      have been difficult to demonstrate. However, the frequency with which Candida
      strains resistant to fluconazole can be isolated appears to be increasing,
      particularly in patients with advanced HIV disease. Anecdotal results suggest
      that patients who fail fluconazole therapy usually do not respond to higher doses
      of fluconazole, but may occasionally respond to itraconazole or ketoconazole. In
      vitro susceptibility to these agents does not necessarily ensure clinical
      efficacy. Amphotericin B is usually effective initially but requires parenteral
      administration. However, with any therapy, relapses tend to occur and
      progressively recalcitrant disease often occurs, with increasing morbidity for
      patients. There is a clear need for studies addressing the incidence of
      resistance, the risk factors for its development, and more effective therapy.

PMID- 7811545
TI  - Wasting syndrome: nutritional support in HIV infection.
AB  - Malnutrition and wasting are common in patients with HIV infection. Nutritional
      needs vary with the stage of HIV disease. Severe weight loss is associated with
      increased mortality in patients with AIDS and is multifactorial in development.
      Possible causes of weight loss include decreased food intake due to oral or GI
      pathology or anorexia, nutrient malabsorption, and systemic infections. Severe
      malabsorption is limited to patients with advanced HIV disease with CD4+ cell
      counts < 100 and usually < 50 cells/microliters. The spectrum of GI pathogens
      continues to broaden. For hypermetabolic patients, evaluation for systemic
      infection followed by effective antiinfective treatment is critical. For
      nonhypermetabolic patients, a variety of metabolic and endocrinological
      abnormalities may be present. It is important to recognize that micronutrient
      deficiencies often accompany macronutrient deficits. Providing appropriate
      nutritional support to patients with AIDS is fundamental to optimal medical care.
      Overall indications for nutritional support in a patient with AIDS are the same
      as in any other chronic disease. Nutritional repletion is well documented, and
      there are a variety of approaches to achieving appropriate intake, including
      volitional (megestrol or dronabinol therapy) and nonvolitional (feeding tubes and
      total parenteral nutrition). Parenteral nutrition should not be undertaken
      without preset limits. The value of nutritional pharmacology with
      supraphysiological doses of micronutrients has not been established.

PMID- 7811546
TI  - Management of the female HIV-infected patient.
AB  - Management of women with HIV infection or AIDS should follow the established
      guidelines for antiretroviral therapy and prevention and treatment of
      opportunistic complications of HIV infection. Gynecological manifestations of HIV
      are primarily cervical dysplasia and cancer associated with human papillomavirus
      (HPV) infection and vaginal and mucocutaneous candidiasis. Human papillomavirus
      associated cervical dysplasia/neoplasia is more common in women with advanced
      rather than early HIV disease, and monitoring with Pap smears should probably
      increase to every 6 months in patients with CD4+ cell counts < 500
      cells/microliter (and certainly when this value falls below 200), with positive
      Pap smears confirmed by colposcopy and biopsy. For patients with CD4+ cell counts
      > 350 cells/microliter, cryotherapy is probably adequate, but therapy should be
      increasingly aggressive at lower CD4+ cell counts. Results of ongoing studies
      should be available soon to guide therapy. Optimal treatment of candidiasis in
      HIV-infected women includes prevention of recurrence with a combination of
      topical and systemic antifungal agents. Women with child-bearing potential should
      be treated as medically indicated for other HIV-infected patients, including
      during pregnancy. In fact, preliminary results of ACTG 076 indicated that
      zidovudine therapy during pregnancy reduces vertical transmission of HIV about
      threefold.

PMID- 7811547
TI  - Glutathione precursor and antioxidant activities of N-acetylcysteine and
      oxothiazolidine carboxylate compared in in vitro studies of HIV replication.
AB  - N-Acetyl-L-cysteine (NAC) and L-2-oxothiazolidine 4-carboxylate (OTC) are pro-GSH
      drugs that been proposed for AIDS therapy. In this article we compare the
      antiviral activities of these compounds in various in vitro HIV infection models.
      Although both compounds blocked cytokine induction of HIV in acute and chronic
      infection models, and in HIV-LTR reporter cell systems, NAC was far more
      effective than OTC, even at suboptimal doses. To test whether this difference is
      due to GSH conversion efficacies of these compounds, we measured GSH restoration
      by NAC or OTC in GSH-depleted peripheral blood mononuclear cells (PBMCs), using
      flow cytometry. In isolated PBMCs, NAC fully replenishes depleted intracellular
      GSH whereas OTC only minimally replenishes GSH. This ability to replenish GSH in
      vitro and its ability to scavenge free radicals directly explain why NAC has more
      potent antiviral activities in vitro.

PMID- 7811548
TI  - Inhibition of AIDS-associated Kaposi's sarcoma cell growth by DAB389-interleukin
      6.
AB  - Acquired immune deficiency syndrome-associated Kaposi's sarcoma (AIDS-KS)-derived
      spindle cells produce and use interleukin 6 (IL-6) among several other cytokines
      as a growth factor. In this study we show that AIDS-KS cells express
      approximately 1100 high-affinity IL-6 receptors (IL-6R) per cell with a
      dissociation constant (Kd) of 110 pM. Furthermore, AIDS-KS cells express the IL
      6R alpha subunit, detected as a single 5.0-kb messenger ribonucleic acid species,
      and the high-affinity converting, signal-transducing IL-6R beta subunit
      designated as gp130. Similarly, tumor tissue obtained from patients with KS and
      AIDS expresses IL-6R messenger ribonucleic acid. We have exploited the chimeric
      fusion toxin DAB389-IL-6, which exerts cellular toxicity only to the cells
      expressing IL-6R. This chimeric protein was engineered by fusion of a truncated
      diphtheria toxin structural gene, in which the region encoding the native
      receptor-binding domain was removed and replaced with the gene encoding IL-6.
      DAB389-IL-6 inhibited protein synthesis in AIDS-KS-derived spindle cells at very
      low concentrations (IC50 of 3.4 x 10(-11) M). Similarly, inhibition of cell
      viability by DAB389-IL-6 was observed at equivalent dose levels (IC50 of 5 x 10(
      11)). These effects on protein synthesis and cell viability can be abrogated by
      recombinant human IL-6, indicating receptor specificity. Thus, DAB389-IL-6 is a
      potential agent for the treatment of AIDS-associated KS.

PMID- 7811550
TI  - Managing the dysfunctional manager in times of change.

PMID- 7811549
TI  - Prospective utility of cerebral proton magnetic resonance spectroscopy in
      monitoring HIV infection and its associated neurological impairment.
AB  - Neurological manifestations of HIV disease occur in most adults and children with
      AIDS. Many of those affected will inevitably suffer clinical neurological
      deficits involving mental function, movement, and sensation. Surprisingly, there
      are not as yet adequate monitoring systems to predict the onset and/or
      progression of HIV infection of the CNS. Neurological, neuropsychological, CSF,
      and magnetic resonance imaging (MRI) analyses cannot accurately detect mental
      deterioration during advancing HIV disease. Reports suggest that in vivo proton
      MR spectroscopy (1H MRS) of the brain could be a predictor of virus-induced
      neurological deterioration. H MRS can measure N-acetylaspartate (NAA), a
      metabolite present only in neurons. Decreased NAA reflects neuronal loss seen
      during HIV infection of brain. To uncover possible associations between NAA
      levels and HIV-induced neurological disease we performed serial 1H MRS brain
      tests in HIV-infected patients with or at risk for encephalopathy. Serial
      testing, for 1 year, of 10 patients showed that brain NAA levels decreased in all
      HIV-infected subjects. The most severe NAA reductions were associated with
      progressive neurological impairment. These findings suggest that NAA can be used
      as a noninvasive measure of neuronal loss in patients with HIV disease. Most
      important, the results suggest that 1H MRS could be used to monitor therapeutics
      directed against HIV infection within the CNS.

PMID- 7811551
TI  - When reengineering causes problems.

PMID- 7811552
TI  - Outcomes management: the evolution of case management in the acute care hospital.

PMID- 7811553
TI  - Walking the talk: operationalizing professional standards into behavioral
      outcomes.

PMID- 7811554
TI  - Measuring the benefits of bedside documentation systems.

PMID- 7811555
TI  - The manipulative manager: a human resources challenge--Part 1.

PMID- 7811556
TI  - Nursing resources on the Internet.

PMID- 7811557
TI  - Radioimmunodetection of cancer of gastrointestinal tract and liver metastasis
      with I-131 anti-CEA and I-131 anti-CA19-9 monoclonal antibody cocktail (IMACIS
      1).
AB  - We evaluated the intravenous infusion of a cocktail of I-131 anti-CEA and anti
      CA19-9 monoclonal antibody F(ab')2 (IMACIS-1) in patients with gastrointestinal
      neoplasm and liver metastases in order to assess its efficacy in detecting the
      presence of cancer. Seven patients with primary or recurrent gastrointestinal
      cancer in whom liver metastases were also detected were studied. Accumulation of
      radioactivity in the primary tumor was seen in only one patient. Visualization of
      the liver metastases was achieved in all patients. Thus detection of liver
      metastasis was better than in primary or recurrent tumors. While tumor
      visualization was most often seen in the 3 day image, optimal visualization of
      the tumor was seen at 5-7 days. There was no correlation between the serum
      concentration of CEA or CA19-9 and the visualization of tumors. Serum kinetics of
      I-131 IMACIS-1 showed biexponential components with a 1st phase T1/2 of 5.0 hours
      and 2nd phase T1/2 of 34.7 hours. The mean whole body (I-131) half-life
      determined from the whole-body scans was 1.95 days. The mean urinary excretion of
      I-131 in 7 days was 85%. This value agreed closely with total radioactivity
      retention detected by scanning. This series of studies demonstrated the potential
      utility of a cocktail of antibodies consisting of an anti-CEA and an anti-CA19-9
      monoclonal F(ab')2.

PMID- 7811558
TI  - Thallium-201 reinjection images can identify the viable and necrotic myocardium
      similarly to metabolic imaging with glucose loading 18F-fluorodeoxyglucose
      (18FDG)-PET.
AB  - We compared the usefulness of 18F-fluorodeoxyglucose (18FDG)-PET with glucose
      loading and thallium-201 (201Tl) reinjection imaging for determining the
      viability of the myocardium in 21 patients with an old anterior myocardial
      infarction. We obtained transaxial views during 201Tl reinjection imaging
      performed 10 minutes after post-exercise injection of 37 MBq 201Tl. PET imaging
      with 75 g oral glucose loading was performed 60 min after injection of 148 MBq of
      18FDG. Wall motion was evaluated by echocardiography. Excellent 18FDG-PET images
      were obtained in 19 of 21 subjects in whom plasma glucose levels were below 251
      mg/dl. The results of 201Tl reinjection imaging and 18FDG-PET imaging were in
      agreement in 20 of the 21 subjects. Echocardiography demonstrated hypokinesis or
      akinesis in segments identified as abnormal in imaging studies. Our results
      showed that 201Tl reinjection imaging identified the viable and necrotic
      myocardium similarly to metabolic imaging obtained by 18FDG-PET with glucose
      loading.

PMID- 7811559
TI  - Noninvasive identification of anthracycline cardiotoxicity: comparison of 123I
      MIBG and 123I-BMIPP imaging.
AB  - To test the feasibility of myocardial 123I-MIBG and 123I-BMIPP imaging for the
      early detection of anthracycline cardiotoxicity, 13 patients who had received
      anthracycline anticancer chemotherapeutic agents were studied. Two-dimensional
      echocardiography and myocardial imaging with both 123I-MIBG and 123I-BMIPP were
      performed in 13 patients treated with anthracycline (group A) and 10 normal
      control subjects (group C). Anterior myocardial images were obtained 15 minutes
      and 3 hours after the injection of isotopes. The heart-to-mediastinum ratio (H/M
      ratio) was used to quantify cardiac 123I-MIBG and 123I-BMIPP uptake. The left
      ventricular shortening fraction (%SF) and the ratio of peak mitral flow velocity
      in early diastole to that at the time of atrial systole (E/A ratio) were measured
      by echocardiography. The H/M ratio of 123I-MIBG was lower in group A than in
      group C (1.5 +/- 0.2 vs. 1.9 +/- 0.2, p < 0.01). The patients in group A had
      faster clearance of 123I-MIBG from the myocardium than those in group C (27 +/-
      10% vs. 22 +/- 4%, p < 0.05). However, the H/M ratio and clearance of 123I-BMIPP
      were similar between the two groups (H/M ratio: 2.1 +/- 0.2 vs. 2.0 +/- 0.2,
      clearance: 24 +/- 6% vs. 26 +/- 6%). The %SF (37 +/- 8% vs. 36 +/- 7%) and E/A
      ratio (1.4 +/- 0.4 vs. 1.6 +/- 0.3) were comparable in groups A and C. The
      present findings indicated that myocardial imaging with 123I-MIBG could detect
      myocardial damage in patients treated with anthracycline in the early stage when
      cardiac systolic and diastolic function was still preserved. Early detection of
      anthracycline cardiotoxicity by 123I-MIBG would reduce the incidence and severity
      of heart failure.

PMID- 7811560
TI  - Comparative evaluation of scintigraphy and upper gastrointestinal tract endoscopy
      for detection of duodenogastric reflux.
AB  - Duodenogastric reflux, the reflux of duodenal bile into stomach, when suspected
      clinically requires an objective evaluation for proper management. In this study
      hepatobiliary scintigraphy in 91 patients of different clinical conditions was
      evaluated for presence of duodenogastric reflux. Upper gastrointestinal endoscopy
      was also performed in 44 of these patients. On scintigraphy duodenogastric reflux
      was present in 26 (29%) of 91 patients. Upper gastrointestinal endoscopy revealed
      presence of refluxed bile in the stomach in 12 (27%) of 44 patients. In the same
      groups of patients scintigraphy detected reflux in 18 (41%) of 44 patients. This
      shows that hepatobiliary scintigraphy is superior to upper gastrointestinal
      endoscopy in detection of duodenogastric reflux and also has the advantage of
      being non-invasive and physiological.

PMID- 7811561
TI  - FDG-PET for predicting the prognosis of malignant lymphoma.
AB  - To evaluate the usefulness of FDG-PET as a predictor of prognosis, 34 patients
      with untreated malignant lymphoma in the head and neck region were studied. After
      FDG-PET and treatment, they were observed from 15 to 50 months. Tumors which were
      aggressive and resistant to treatment tended to show high uptake of FDG. The
      survival rate of patients with high uptake of FDG, DAR > or = 8, was lower than
      the rate of the other patients. It is considered to be useful to add FDG uptake
      of the tumor to other prognostic factors for predicting the prognosis.

PMID- 7811562
TI  - In vivo kinetics of 99mTc labeled recombinant tissue plasminogen activator in
      rabbits.
AB  - Our previous studies demonstrated that 99mTc labeled recombinant tissue
      plasminogen activator (rt-PA) retained high affinity with fibrin in vitro but
      showed unexpectedly low uptake in fresh thrombi in vivo. The present study was
      performed to determine the in vivo kinetics of radiolabeled t-PA in the rabbit.
      Sequential images and blood samples after the intravenous administration of 99mTc
      labeled rt-PA in thrombus-bearing rabbits were taken. The radioactivity and
      immunological level of t-PA and PAI-1 in the solution eluted to each fraction by
      gel permeation chromatography were measured by means of a well scintillation
      counter and enzyme-linked immunosorbent assay (ELISA). Most of the radioactivity
      was eluted in the fraction (Fr. 7) of larger molecular weight than that (Fr. 9)
      of intact t-PA. The level of intact rt-PA was increased with a regimen involving
      the preadministration of cold rt-PA which was followed by the administration of
      hot rt-PA. The level of PAI-1 in plasma showed an increased rebound 15 minutes
      after the intravenous injection. These results suggest two possible reasons why
      rt-PA retains high affinity with fibrin in vitro, once radiolabeled, but was
      ineffective in delineating fresh thrombi with a gamma camera: 1) some plasma
      components such as PAI-1 combine with circulating radiolabeled rt-PA and form a
      larger molecule immediately and/or 2) radiolabeled rt-PA is modulated as a
      consequence of the radiolabeling and forms a larger molecule than intact rt-PA.

PMID- 7811563
TI  - Comparison of anatomical standardization methods regarding the sensorimotor foci
      localization and between-subject variation in H2(15)O PET activation, a three
      center collaboration study.
AB  - Identical sets of H2(15)O-PET brain activation data regarding vibrotactile
      stimulation and voluntary motion of the fingers in seven young normal subjects,
      together with the MRI, were analyzed in three PET centers by means of each
      center's own method of anatomical standardization to Talairach's frame. Every
      center used a linear or segmentally linear transformation with various number of
      scaling factors. A variation of 6-8 mm in each axis was observed in the foci
      localization due to the difference in the transformation principle and the
      measured brain size. Between-subject variation was similar in all the centers.
      Since different standardization methods define different coordinate systems, a
      cautious attitude should be taken to comparing results analyzed at different
      centers.

PMID- 7811564
TI  - Impaired hepatic function in segmental biliary obstruction demonstrated with a
      receptor-binding radiotracer.
AB  - A patient with cholangiocarcinoma underwent left-sided cholangiojejunostomy, and
      hepatic functional imaging with a receptor-binding radiotracer and SPECT was
      performed to evaluate the distribution of functional reserve. It revealed
      decreased accumulation in the regions with residual dilatation of the
      intrahepatic bile ducts, indicating several kinds of focal damage in hepatic
      function caused by segmental biliary obstruction. The radioligand may be useful
      in assessing regional hepatic function, and the high spatial resolution provided
      by SPECT appears to play an important role for this purpose.

PMID- 7811566
TI  - Thrombolytic therapy in experimental embolic stroke.
AB  - The effect of thrombolytic therapy is well-documented in acute myocardial
      infarction. In acute cerebral infarction, thrombolytic therapy has been evaluated
      in small series of patients. The point of thrombolytic therapy is to avoid or
      reduce ischemic damage of neuronal tissue by rapid arterial recanalization. In
      thrombolytic therapy of cerebral vascular occlusion, the pathophysiology of
      reperfusion needs further investigation and documentation. This review describes
      studies of thrombolysis in embolic stroke using animals embolized by intracarotid
      injections of blood clots. Vascular occlusion was demonstrated by angiography and
      measurement of cerebral blood flow. Thrombolytic therapy with recombinant tissue
      type plasminogen activator was initiated after varying periods of time.
      Reperfusion, cellular function, and brain damage were examined by angiography and
      by clinical and pathoanatomical examination. Based mainly on results from our own
      investigations, the following theses concerning ischemic stroke were made: (a)
      Cerebral infarction caused by arterial occlusion is due to delayed, incomplete,
      or no reperfusion. Spasms, or hemodynamic mechanisms, seem to be of only minor
      importance. (b) Early thrombolytic therapy in animal models increases the degree
      of reperfusion and reduces brain damage, clinical deficits, and mortality. (c)
      Early arterial reperfusion reduces cerebral infarction and related edema. With
      early reperfusion, the extent of brain damage correlates to the length of the
      delay from onset of ischemia. (d) Cerebral stunning is caused by arterial
      occlusion followed by very early spontaneous or induced reperfusion, as neurons
      temporarily lose their functional capabilities without dying. (e) Multiple
      embolic microclots in experimental stroke result in more brain damage than a
      single macroclot, and with clots the extent of brain damage is dependent on the
      structural composition and volume of emboli. (f) The ability to recanalization in
      experimental embolic stroke is related to the amount of red cells in the emboli
      and inversely related to the volume of emboli and to the fibrin content and
      density of the clots. (g) Infarct-limiting effects in experimental stroke can be
      obtained by ischemic neuroprotectants or by hypothermia, either alone or with
      thrombolytic therapy, which then reduces brain damage further.

PMID- 7811565
TI  - Accumulation of L-[2-(F-18)]fluorophenylalanine in peri-infarct area in a patient
      with acute cerebral infarction.
AB  - We studied the brain uptake of amino acid in a patient with acute cerebral
      infarction with L-[2-(F-18)]fluorophenylalanine and positron emission tomography.
      The increased accumulation of the ligand was specifically found in the peri
      infarct area where oxygen metabolism was still maintained but decreased later in
      the 72-day follow-up period. The kinetic analysis revealed that increased
      accumulation was not due to increased transport from the blood to the brain but
      delayed washout from the brain to the blood. Although the mechanism is still
      unknown, abnormally high accumulation of L-[F-18]fluorophenylalanine may predict
      delayed neuronal changes after ischemic insults of the brain.

PMID- 7811567
TI  - Bacillus cereus in infant foods and dried milk products.
AB  - Dried milk products and infant food are known to be frequently contaminated with
      Bacillus cereus. Sources of the organism and its behaviour in the product and in
      the equipment during processing are discussed. With regard to the incidence of B.
      cereus in infant food, 261 samples distributed in 17 countries were collected and
      examined for its B. cereus content. Fifty-four percent of the samples were
      contaminated with B. cereus reaching levels from 0.3 to 600/g. Counts higher than
      10/g were found in only 27 samples (10%). Most of the positive samples (44%)
      contained 0.3 to 10 B. cereus/g. Four samples (1.5%) were contaminated with more
      than 100 organisms/g reaching a maximum level of 600 B. cereus/g. When classified
      into different types of products about 50% of the infant formulae based on milk,
      the follow-on formulae and the weaning foods were contaminated with B. cereus as
      well as 69% of those based on soy protein and 92% of the special dietetic foods.
      Compared to our earlier studies from 1982/83, the percentage of contaminated
      samples from Germany increased from 31% to 70% in the case of infant formulae,
      from 28% to 55% in the case of follow-on formulae, and from 40% to 100% in the
      case of special dietetic food. The percentage of weaning food contaminated with
      B. cereus remained nearly unchanged. It should be stressed, however, that the
      numbers of B. cereus were almost the same in both studies with the highest count
      in 1982/83 being 460 and in 1992 600/g. Samples naturally contaminated with
      counts of about 100 B. cereus/g were reconstituted and incubated at a room
      temperature of 27 degrees C. Levels of 10(5) B. cereus/g were reached after 7-9
      h. Toxigenicity of B. cereus in dried milk products and infant food as well as
      food poisoning outbreaks attributed to B. cereus are discussed.

PMID- 7811568
TI  - Stability of spores of Bacillus cereus stored on silicagel.
AB  - Spores of four different strains of Bacillus cereus were stored on silicagel at
      22 degrees C and in physiological saline solution at -20 degrees C for a period
      of 260 days. At different intervals the spores were tested for survival, heat
      sensitivity and capacity to germinate. There was no clear change in any of the
      parameters tested, so storage on silicagel can be a good alternative for storage
      as a frozen suspension. Spores stored in this way can easily be exchanged for
      reference material and used for microbiological challenge testing.

PMID- 7811569
TI  - Prevalence of Listeria monocytogenes in foods in Malaysia.
AB  - A total of 234 samples of food, consisting of 158 of raw and 76 samples of ready
      to-eat food were examined for the presence of Listeria monocytogenes. The
      frequencies of L. monocytogenes contamination in raw foods were: chicken portions
      (60%), liver (60%) and gizzard (62%), beef (50%), beansprout (85%), prawns (44%),
      kupang (dried oysters) (33%), bean cake (25%), satay (48%) and leafy vegetables
      (22%). Of the ready-to-eat foods: satay (26%), prawns, squids, clams and chicken
      dishes (22%), cucumber (80%) and peanut sauce (20%) were found to yield L.
      monocytogenes.

PMID- 7811570
TI  - Presence, detection and growth of Listeria monocytogenes in seafoods: a review.
AB  - Listeria monocytogenes and other Listeria spp. have been isolated from seafoods
      on a regular basis since 1987. A relatively high incidence of the organism (6
      36%) in ready-to-eat cold smoked salmon and cooked fish products has raised
      concern about the survival and growth potential of this organism in seafoods, as
      these products are not processed further before consumption. L. monocytogenes
      grows well at refrigeration temperature on most seafoods, but the sources of
      contamination in ready-to-eat fish products are still unknown. This paper reviews
      the knowledge available in order to make recommendations on control options and
      avenues for future research.

PMID- 7811572
TI  - Characterization of dairy-related Bifidobacterium spp. based on their beta
      galactosidase electrophoretic patterns.
AB  - Numerical analysis of phenotypic characteristics based on enzymatic activity and
      carbohydrate fermentation allowed the discrimination of most strains of
      bifidobacteria of animal origin from those of human origin. Strains of
      bifidobacteria studied were separated into nine groups based on numerical
      analysis. Three groups contained most strains of animal origin, three groups
      comprised both strains of animal and human origin, and three groups were strictly
      composed of strains of human origin. The results indicate that one group of
      animal origin (group II) contained all reference strains of Bifidobacterium
      animals and 10 strains isolated from fermented milks or commercial preparations.
      Although numerical analysis of enzymatic activities and carbohydrate fermentation
      patterns allowed the differentiation of 'wild' strains of B. animalis and B.
      longum isolated from commercial preparations, this method failed to confirm the
      species. In the present study, the determination of electrophoretic patterns of
      beta-galactosidases resulted in the development of a new technique for the
      differentiation of Bifidobacterium species. Several isoenzymes of beta
      galactosidase were detected among strains of bifidobacteria. Each species had a
      specific electrophoretic pattern. The detection of beta-galactosidase by
      electrophoresis is a new tool for distinguishing between dairy- and non-dairy
      related bifidobacteria. Dairy-related bifidobacteria (B. bifidum, B. breve, B.
      infantis and B. longum) as well as B. animalis could be better differentiated
      from other bifidobacteria by comparison of their beta-galactosidase
      electrophoretic patterns, rather than by numerical analysis of their phenotypic
      characteristics.

PMID- 7811571
TI  - The normal mycoflora of commodities from Thailand. 2. Beans, rice, small grains
      and other commodities.
AB  - Part of a comprehensive study of fungi occurring in commodities in Thailand, this
      paper reports results from 276 samples of mung beans, rice, sorghum and soybeans
      as well as other minor crops. Samples for major commodities were taken from
      farmers' stocks, middlemen and retail outlets, while those for minor crops were
      mostly from retail. Each sample was divided into two portions, one being examined
      in Bangkok and the second at North Ryde. Mycological examinations were carried
      out by direct plating after surface disinfection in chlorine. Media used were
      dichloran rose bengal chloramphenicol agar, dichloran 18% glycerol agar,
      Aspergillus flavus and parasiticus agar and dichloran chloramphenicol peptone
      agar. Fungi were identified to species level and percentage infection of samples
      calculated. The dominant fungus found in mung beans was Fusarium semitectum,
      which was present in 40% of samples and at a high level (18% of all seeds)
      overall. Aspergillus flavus was also found in 40% of samples, but only in 2% of
      seeds overall. Lasiodiplodia theobromae was the only other fungus exceeding 1%
      total infection. The major fungi found in soybeans were A. flavus (67% of
      samples; 6% overall) and Cladosporium cladosporioides (49% of samples; 9%
      overall). Storage fungi were more common in soybeans than the other commodities,
      indicating longer or adverse storage. Paddy rice contained high levels of a wide
      variety of field fungi, notably Fusarium semitectum, Bipolaris oryzae, and
      Curvularia, Phoma and Colletotrichum species. However, probably due to the heat
      generated by milling, milled rice contained very few fungi, which were mostly of
      storage origin. Only 3% of particles examined contained internal fungi. Infection
      in sorghum was typical of oilseeds, dominated by Aspergillus flavus, which was
      present in 86% of samples, with an overall infection rate of 12%. Beans other
      than soybeans were infected by a wide range of field fungi, but at low levels,
      with less than half of seeds examined being infected internally. With the
      exception of sorghum, the levels of mycotoxigenic fungi encountered were much
      lower than observed previously in nuts and oilseeds.

PMID- 7811573
TI  - Growth of Enterococcus, Lactococcus and Streptococcus strains and environmental
      isolates in liquid media and their reactions on BEEA.
AB  - Growth of known species of Enterococcus, Lactococcus and Streptococcus and
      Aerococcus viridans in selective and nonselective liquid media routinely used to
      enumerate faecal streptococci was measured optically at different temperatures.
      Growth of environmental isolates was measured in some of these media. Growth of
      the reference strains on Bile esculin azide agar at elevated incubation
      temperatures was tested. The results revealed only minor differences between
      media but strong influence of incubation temperature. Some media tended to yield
      higher cell densities than others. For many species the inoculum size affected
      maximum turbidity. To combine selective media with selective incubation
      temperatures seems to be necessary to achieve satisfactory reliability in
      traditional liquid enumeration methods for faecal streptococci. Because of the
      diversity of this group, optimal selectivity and recovery can hardly be achieved
      simultaneously.

PMID- 7811574
TI  - Growth and verotoxin 1 production by Escherichia coli O157:H7 in ground roasted
      beef.
AB  - Production of verotoxin 1 (VT1) by hemorrhagic Escherichia coli O157:H7 in food
      has received limited research attention. A study was therefore conducted to
      determine the effect of temperature and pH, as achieved using two different
      acidulants, on VT1 production in ground roasted beef slurry. Slurries (pH 5.9)
      containing 33% beef and 67% water were incubated at 21 degrees C or 37 degrees C.
      Transfers were made at 48-h intervals for up to 18 days to determine if repeated
      subculturing influenced VT1 production. Populations of E. coli O157:H7 ranged
      from 8.9 x 10(8) to 1.9 x 10(9) CFU/ml within 48 h of transfer, regardless of
      incubation temperature. Maximum VT1 concentrations ranged from 61 to 63 ng/ml and
      63 to 85 ng/ml of slurries incubated at 21 degrees C and 37 degrees C,
      respectively. The amount produced within 48 h at 37 degrees C was 15-24% higher
      than the amount produced at 21 degrees C and did not change after ten successive
      48-h transfers. Upon changing the incubation temperature of slurry cultures
      adapted to 21 degrees C to an incubation temperature of 37 degrees C, VT1
      production increased within 48 h to the level of cultures which had been
      previously adapted to 37 degrees C. A shift in temperature from 37 degrees C to
      21 degrees C resulted in an initial reduction of about 55% in the amount of VT1
      produced within 48 h. For studies on the combined effect of incubation
      temperature, pH and acidulant, slurries were adjusted to pH 5.4 with acetic and
      citric acids. Growth and production of VT1 in slurry acidified with acetic acid
      was markedly reduced compared to that in the control slurry (pH 5.9). The amount
      of VT1 detected in slurries receiving the second and third 24-h transfer of
      culture incubated at 21 degrees C was essentially nil. Growth and VT1 production
      was reduced in slurry acidified with citric acid compared to that observed in the
      control slurry but not as drastically as that observed in slurry acidified with
      acetic acid. VT1 concentration in unacidified beef slurry (pH 5.9) and in beef
      slurry acidified at pH 5.4 with citric acid reached 21 and 16 ng/ml,
      respectively, within 24 h at 21 degrees C. Results emphasize the need for proper
      sanitation procedures in beef processing and preparation facilities to reduce the
      risk of cross contamination of roasted beef and subsequent growth of E. coli
      O157:H7 and VT1 production.

PMID- 7811575
TI  - A comparison study of the EF-18 agar/Hydrophobic Grid Membrane Filter (HGMF)
      method and the enzyme linked antibody (ELA)/HGMF method to the HPB standard
      method in the isolation of Salmonella.
AB  - As part of a comparative and collaborative study of rapid methods for the
      detection of Salmonella and the standard Health Protection Branch (HPB) method,
      six Federal and Provincial Laboratories compared the EF-18 agar/Hydrophobic Grid
      Membrane Filters (HGMF) method to the standard HPB method. Two Federal
      Laboratories also compared the enzyme linked antibody (ELA)/HGMF method (which is
      a further development of the EF-18 agar/HGMF method) to the standard method.
      During this study the false-negative rates ranged from 0% to 15% for the standard
      HPB method, from 5.88% to 43.5% for the EF-18 agar/HGMF method, and from 0% to
      10.5% for the ELA/HGMF method. The EF-18 agar/HGMF method did not compare well
      with the standard HPB method due to the number of false-negatives. Problems with
      this method resulted from the inability to isolate colonies of Salmonella on the
      HGMF due to the small colony size, abnormal colony coloration, and overgrowth by
      competitors. The ELA/HGMF method, however, was shown to be comparable to the
      standard HPB method. The main advantages of this method are that the antibody
      staining step is independent of colony coloration and carbohydrate utilization on
      the plating media; the ability to detect some unusual strains of Salmonella
      irrespective of their atypical reactions on the media; and the ELA staining can
      indicate the presence of Salmonella even when the HGMF is overgrown by
      competitors. Also, cultural confirmation can proceed simultaneously yet
      independently of the ELA staining procedure. The data presented here indicate
      that this method is worth further study.

PMID- 7811576
TI  - Characteristics of Bacillus cereus related to safe food production.
AB  - Thirty Bacillus cereus strains, isolated from different sources, were
      characterized in relation to safe food production. The minimal growth
      temperatures of the strains varied from < or = 5 degrees C to 11 degrees C.
      Generation times at 7 degrees C of strains capable of growing at temperatures <
      or = 5 degrees C were approximately 8.2 h. The D90 degrees C-values of spores of
      strains with a minimal growth temperature of 11 degrees C determined in phosphate
      buffer at pH 7.0 ranged from 4.8 to > 200 min. Strains with the capacity to grow
      at temperatures < or = 9 degrees C, had a D90 degrees C value ranging from 4.6 to
      14 min. Addition of either nisin (250 micrograms/ml) or diacetyl (1500
      micrograms/ml) to the heating menstruem at the single concentrations investigated
      seemed not influence the thermal destruction of spores. Germination of spores of
      almost all strains occurred in all three media tested (Brain Heart Infusion, rice
      extract and milk) even at temperatures below the minimal growth temperature. All
      B. cereus strains tested yielded positive results with a commercial test kit for
      diarrhoeal enterotoxin. The results indicate that strains with the capacity to
      grow at temperatures < or = 7 degrees C are not essentially different from those
      with minimal growth temperatures of > 10 degrees C.

PMID- 7811577
TI  - Surgical treatment of extracranial internal carotid artery aneurysm.
AB  - Aneurysms of the extracranial internal carotid artery are rare but can be
      responsible for severe complications such as rupture, thrombosis, or embolism.
      Between 1961 and 1985 we operated on 38 aneurysms of the extracranial internal
      carotid artery in 35 patients, 22 males and 13 females, whose ages ranged from 6
      to 73 years. The underlying causes of aneurysm included atherosclerosis (12
      cases), fibromuscular dysplasia (eight cases), a congenital defect (five cases),
      infection (one case), and trauma (six cases); in six cases aneurysm was secondary
      to spontaneous dissection. Signs of cerebral ischemia were present in 26 (74%)
      patients and a cervical mass was found in six. The aneurysm was proximal (i.e.,
      below the angle of the mandible) in 16 patients and distal (i.e., above the angle
      of the mandible) in 22. After resection of the aneurysm, arterial continuity was
      restored in 37 patients by resection and grafting (12 cases), resection and
      anastomosis (11 cases), or arteriorrhaphy (14 cases). One death occurred 13 days
      after operation due to myocardial infarction. Two patients experienced a
      reversible neurologic event. Transient paresis of cranial nerves was observed in
      eight patients. During a follow-up period that ranged from 6 to 30 years, four
      patients were lost to follow-up and 25 patients remained asymptomatic. Three
      patients had asymptomatic thrombosis of the carotid artery detected at follow-up
      investigations. The potential risks of cerebral ischemia and rupture and the
      satisfactory long-term results achieved with surgery are strong arguments in
      favor of surgical treatment for aneurysms of the extracranial internal carotid
      artery.

PMID- 7811578
TI  - Carotid endarterectomy in the octogenarian.
AB  - During a 10-year period from January 1983 to December 1992, 79 carotid
      endarterectomies were performed in patients aged 80 years or older. This
      represented 7.4% of the total patient population undergoing carotid
      endarterectomy at Emory University Hospital. The indications for surgery in this
      elderly population were transient ischemic attacks in 24 (30.3%), cerebrovascular
      accident in 12 (15.2%), amaurosis fugax in seven (8.9%), vascular tinnitus in one
      (1.3%), and asymptomatic stenosis in 35 (44.3%). The average degree of
      ipsilateral stenosis was 76.8%. Concomitant risk factors included coronary artery
      disease in 43%, systemic arterial hypertension in 51.9%, diabetes mellitus in
      10.1%, and significant smoking history in 53.2%. Seventy-six percent of the
      procedures were performed under local anesthesia, and in all but two intraluminal
      shunts were used. Combined 30-day mortality and postoperative stroke morbidity in
      this population was 1.3% (one patient). Long-term follow-up ranging from 1 to 10
      years (average 35 months) revealed no ipsilateral strokes. This experience
      suggests that carotid endarterectomy can be performed in an elderly population
      with morbidity and mortality rates similar to those in a younger cohort.

PMID- 7811579
TI  - Carotid surgery in the octogenarian.
AB  - The records of 52 patients aged 80 years or older who underwent 56 carotid artery
      reconstructions were analyzed retrospectively. Four patients had amaurosis fugax,
      27 patients had experienced one or more transient ischemic attacks, eight had a
      completely or partially reversible stroke, and 10 had vertebrobasilar
      insufficiency. Three patients were asymptomatic. Arteriograms documented stenosis
      > 80% on the operated side in 48 cases, whereas the contralateral carotid artery
      was occluded or had > 80% stenosis in 10 cases each. Two or more cerebral
      arteries were involved in 37 patients. CT scans were normal in only 21 (40%)
      patients. General anesthesia was used in 54 of 56 operations. Thirty-six
      endarterectomies, 18 bypasses, and two resection-anastomoses (for tortuosity)
      were performed. A shunt was employed in eight (14.3%) cases. One lethal stroke
      (1.9%) occurred during the first postoperative month. Three patients experienced
      nonfatal strokes, two of which gave rise to residual deficits. Two patients were
      lost to follow-up. For the remaining 49 patients the mean follow-up was 24
      months. Two-year actuarial survival was 76.3% for the entire series and 67% for
      those surviving without neurologic events. This study shows that when properly
      selected the elderly population can safely undergo carotid surgery.

PMID- 7811580
TI  - Outcome of carotid endarterectomy performed at a community medical center.
AB  - From 1990 to 1992 there was a 43% increase in the number of carotid
      endarterectomies (CEAs) performed at our institution. Not coincidentally the
      North American Symptomatic Carotid Endarterectomy Trial study was published in
      August 1991. To determine whether CEAs could be performed safely at community
      medical centers, records of 181 consecutive CEAs performed during a 30-month
      period at a suburban community medical center were reviewed. CEAs were performed
      by 14 surgeons: six vascular, three thoracic, and five general surgeons. Among
      all patients 87% had lesions with > or = 70% stenosis. Seventy percent of CEAs
      were performed on symptomatic patients, 84% of whom had stenoses > or = 70%.
      Among asymptomatic patients 96% had stenoses > or = 70%. There were five
      instances of neurologic complications in the perioperative period--two transient
      ischemic attacks, two reversible ischemic neurologic deficits, and one permanent
      neurologic deficit. One patient died. The mortality rate was 0.6%, the combined
      major stroke/mortality rate was 1.2%, and the any stroke/mortality rate was 2.2%.
      There were five patients with nonfatal major complications--one with myocardial
      infarction, one with pulmonary edema, one with congestive heart failure, and two
      with postoperative arrhythmia. Thirteen minor complications included eight cases
      of cranial nerve dysfunction. These data demonstrate that CEAs can be performed
      safely at community medical centers.

PMID- 7811581
TI  - Use of endovascular stents for acute aortic dissection: an experimental study.
AB  - This study was designed to evaluate the potential obliteration of an experimental
      aortic dissection using an intravascular stent introduced via the femoral artery.
      Twenty-two adult dogs were divided into four groups: in group A (n = 6) a
      thoracoabdominal aortic dissection was surgically created to observe the natural
      course of this lesion; in group B (n = 6) a nitinol coil graft was introduced
      into the aorta via the femoral artery; in group C (n = 3) a nitinol coil graft
      was introduced via the femoral artery into a dissected aorta in an attempt to
      obliterate the dissection; and in group D (n = 7) an expandable intraluminal
      vascular graft (Palmaz stent) was introduced via the femoral artery into a
      dissected aorta in an attempt to obliterate the dissection. Arteriographic
      evaluation was performed postoperatively and again 6 weeks later before the
      aortas were explanted. Gross and light microscopic examinations were performed on
      all explanted aortas. In group A dissection was achieved and a postoperative
      aortogram demonstrated evidence of aortic dissection in all animals. Autopsy
      revealed persistence of dissection with a reentry tear near the celiac axis in
      five animals. In group B there was incomplete expansion of the nitinol coil graft
      in five dogs, resulting in aortic thrombosis in one. In group C the nitinol coil
      graft failed to obliterate the aortic dissection in all animals and resulted in
      aortic thrombosis in two. In group D placement of a balloon-expandable
      intraluminal stent solely at entry and reentry sites resulted in only partial
      obliteration of the dissection (n = 3), but when the entire length of the
      dissected aorta was treated, the dissection was completely obliterated (n = 3).

PMID- 7811582
TI  - Thrombogenicity of an elastomer-coated aortofemoral Dacron prosthetic graft in
      humans.
AB  - To determine the potential benefit of Dacron prostheses impregnated with silicon
      polymer, an elastomer-coated prosthetic graft (Intervascular [I]) was implanted
      in 30 patients with aortic occlusive arterial disease or infrarenal abdominal
      aortic aneurysm. These patients were compared with two other groups who underwent
      vascular reconstruction with either a knitted double-velour prosthesis (Meadow
      [M] or a knitted prosthesis (Bard-USCI [U]). The different prostheses were
      randomly allocated just prior to their insertion. Average blood loss was 1063.33
      +/- 1065.69 ml for the I group, 888.33 +/- 575.85 ml for the M group, and 908.33
      +/- 471.80 ml for the U group (NS). The duration of the operation was 160 +/- 56
      minutes for the I group, 142 +/- 37 minutes for the M group, and 153 +/- 65
      minutes for the U group (NS). The average follow-up was 12 months. As calculated
      by the actuarial method, primary patency at 36 months was 71.5% for the I group,
      100% for the M group, and 98.2% for the U group (p < 0.001). Secondary patency
      was 73.7% for the I group and 100% for the M and U groups, respectively (p <
      0.001). This study shows that the thrombogenicity of the elastomer-coated
      aortofemoral vascular prosthetic graft was significantly higher than that of the
      two other prostheses. Increased intraoperative blood loss and longer duration of
      operation were related to the aortic abnormality being treated (aneurysm or
      occlusion) rather than to the type of prosthetic graft being used.

PMID- 7811583
TI  - Preservation of cortical microcirculation after kidney ischemia-reperfusion:
      value of an iron chelator.
AB  - Treatment of suprarenal aneurysms and renal artery reconstructions are both
      responsible for normothermic ischemia of the kidney (during clamping) followed by
      reperfusion (declamping). During reflow through an organ undergoing ischemia the
      production of free radicals can be associated with cell injury and a no-reflow
      phenomenon characterized by perfusion defects after a period of transient
      hyperemia. The objectives of this study were to demonstrate the existence of this
      phenomenon in the kidney undergoing ischemia followed by reperfusion and to test
      the potential protection afforded by an iron chelator (desferrioxamine) since
      free radical reactions are catalyzed by iron. Adult New Zealand white rabbits
      were divided into the following three groups: group A, 15 minutes of ischemia
      plus 10 minutes of reperfusion; group B, 60 minutes of ischemia plus 10 minutes
      of reperfusion; and group C, 60 minutes of ischemia plus 10 minutes of
      reperfusion combined with infusion of desferrioxamine (50 mg/kg). Cortical
      microcirculation in the kidney was measured by laser Doppler flowmeter before
      ischemia and 1, 5, and 10 minutes after reperfusion. Vitamin E content was
      determined in the cortex of the left kidney after 10 minutes of reperfusion and
      compared with that of the right (control) kidney. After 1 minute of reperfusion
      the cortical microcirculatory flow was significantly increased in all three
      groups (reactive hyperemia). In groups A and C blood flow returned to preclamping
      values after 10 minutes of reperfusion; however, blood flow in group B remained
      significantly reduced (29.2% +/- 10.5%) after 5 minutes of reperfusion with a
      further reduction to 48.5% +/- 5.7% after 10 minutes. These findings were
      correlated with the dosage of vitamin E since the vitamin E content was greatly
      reduced by 46.7% +/- 7.8% in group B but did not change significantly in groups A
      and C. This study shows that 60 minutes of normothermic ischemia is followed by a
      significant reduction in cortical microcirculatory flow (no-reflow phenomenon).
      Infusion of an iron chelator (desferrioxamine), however, which decreases the
      intensity of lipid peroxidation induced by the free radicals, preserves the
      microcirculatory flow.

PMID- 7811584
TI  - Epidural spinal cord stimulation in the treatment of severe peripheral arterial
      occlusive disease.
AB  - Epidural spinal cord stimulation (ESCS) has been suggested to improve
      microcirculatory blood flow and reduce amputation rates in patients with severe
      peripheral arterial occlusive disease (PAOD). Pain relief, limb salvage, and skin
      circulation were studied in 177 patients with ischemic pain caused by
      nonreconstructible PAOD who were receiving ESCS. Medical or surgical therapy had
      failed and vascular reconstruction was impossible in all cases. Clinical status
      was classified as Fontaine's stage III (chronic ischemic rest pain) in 114
      patients and Fontaine's stage IV (ischemic pain and ulcers or dry gangrene) in 63
      patients. PAOD was essentially due to arteriosclerosis, but 36 patients also had
      diabetic vascular disease. After a mean follow-up of 35.6 months, significant
      pain relief (> 75%) with limb salvage was achieved in 110 patients. In 11
      patients with limb salvage, pain alleviation was determined to be between 50% and
      70%. ESCS was ineffective in reducing pain, leading to major amputation in 56
      patients. The cumulative limb salvage rate was 66% at 4 years. The systolic
      ankle/brachial blood pressure index did not change under stimulation. TcPO2 was
      assessed on the dorsum of the foot. Clinical improvement was associated with
      increased TcPO2, with limb salvage improving from 24.2 to 48.1 mm Hg in stage III
      (p < 0.02) and from 16.4 to 37.2 mm Hg in stage IV (p < 0.03) disease. A TcPO2
      increase of more than 50% within the first 3 months after implantation was
      predictive of success. TcPO2 changes are correlated with the presence of adequate
      paresthesias in the painful area during the trial period.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7811585
TI  - Femoropopliteal bypass with either adequate ipsilateral reversed saphenous vein
      or obligatory polytetrafluoroethylene.
AB  - The results are presented of a 10-year experience with 312 femoropopliteal
      bypasses performed in 285 patients using ipsilateral autologous reversed greater
      saphenous vein when available and adequate and polytetrafluoroethylene (PTFE)
      when not. The indications for operation were severe claudication in 121 (39%),
      rest pain in 95 (30%), and minor tissue loss in 96 (31%) limbs. There were 235
      (75%) saphenous vein bypasses, of which 157 were above and 78 below the knee, and
      77 (25%) PTFE bypasses, 58 above and 19 below the knee. Of these, 232 (79%)
      saphenous vein and 62 (21%) PTFE bypasses were primary procedures. The 30-day
      mortality rate was 3% (7/285) and the 30-day amputation rate was 2% (6/312).
      Overall, 24 (10%) saphenous vein and 30 (39%) PTFE grafts ultimately failed. The
      cumulative primary patency of all bypasses was 77% +/- 4% (mean +/- 1 SE) (85% to
      69%, 95% confidence interval) at 3 years and 75% +/- 4% (86% to 64%) at 5 years.
      Saphenous vein primary patency was superior to that of PTFE at 3 years, 87% +/-
      4% (97% to 77%) vs. 54% +/- 12% (65% to 41%), (p < 0.01), and at 5 years, 81% +/-
      6% (96% to 67%) vs. 48% +/- 16% (63% to 33%) (p < 0.01). Above-knee saphenous
      vein bypass primary patency was slightly better than below-knee patency at 3
      years, 89% +/- 4% vs. 84% +/- 6%, and at 5 years, 83% +/- 7% vs. 80% +/- 8%. This
      was superior to above-knee PTFE patency at 3 years, 54% +/- 14%, and at 5 years,
      34% +/- 16% (p < 0.01). The overall PTFE failure rate was three to four times
      that of the saphenous vein rate. These results strongly support the use of
      autologous greater saphenous vein for all femoropopliteal bypasses when it is
      available and of good quality. PTFE grafts are valuable secondary conduits when
      the vein is not available or is inadequate. This series was not randomized since
      PTFE was used only in patients with inadequate or unavailable ipsilateral greater
      saphenous veins. When this protocol was followed, the patency rate for greater
      saphenous vein was excellent and its use is recommended for femoropopliteal
      bypass when it is available and of good quality.

PMID- 7811586
TI  - Acute dissection of the aorta in a kidney transplant patient.
AB  - Acute type IIIb dissection of the aorta was observed in a patient who had
      undergone kidney transplantation 5 years previously. Arteriograms showed that the
      true channel was compressed by the false channel, excluding the right common
      iliac artery to which the renal artery of the transplanted kidney had been
      anastomosed. The patient was treated successfully by fenestration of the
      abdominal aorta.

PMID- 7811587
TI  - Acute aortic dissection into a preexisting abdominal aortic aneurysm.
AB  - Acute aortic dissection and abdominal aortic aneurysm presenting as coexistent
      conditions is rare. We report a patient with a history of hypertension and acute
      severe back pain who had an acute aortic dissection extending into a preexisting
      8 cm abdominal aortic aneurysm that was diagnosed by CT scan. There was no
      evidence of aortic rupture or leakage. The patient was treated with
      antihypertensive medication for 2 months to allow maturation of the acute
      dissection prior to elective repair of the abdominal aortic aneurysm. The repair
      was constructed to allow continued perfusion of both the true and false lumina by
      fenestration of the aortic septum at the proximal anastomosis. There were no
      postoperative complications. This case illustrates an unusual combination of
      aortic diseases. A management plan is described that safely treats both
      pathologic conditions.

PMID- 7811588
TI  - Primary aortocaval fistula in association with ruptured aneurysms.
AB  - We report three cases in which ruptured aneurysm and aortocaval fistula went
      undetected until surgery was performed. Preoperative features suggestive of an
      arteriovenous fistula were not apparent in any of these patients; they all
      presented with cardiovascular collapse and all underwent emergency laparotomy
      after a ruptured abdominal aortic aneurysm was diagnosed. The fistula was
      discovered unexpectedly only after the aneurysmal sac was opened and the thrombus
      evacuated. In the first two patients the fistula was successfully sutured from
      within the aneurysmal sac. The first patient died 1 week postoperatively from
      rupture of a previously known associated thoracic aortic aneurysm and the second
      patient died during the operation from excessive blood loss. The third patient
      had a large fistula requiring an interposition synthetic graft to restore the
      continuity of the vena cava; the graft has remained patent 15 months
      postoperatively. Aortocaval fistula is an uncommon complication of aneurysmal
      aortic disease and may coexist with a rupture of the aneurysm into the
      retroperitoneum. In emergency cases such as ours it is usually discovered
      unexpectedly during the operation. The established method of treatment is to
      oversew the fistula from within the aneurysm; however, when the fistula is large
      reconstruction of the infrarenal inferior vena cava with an interposition
      synthetic graft is a good alternative to caval ligation.

PMID- 7811589
TI  - Iliac aneurysm in a child complicating umbilical artery catheterization.
AB  - We report a case of an iliac artery aneurysm in a 9-year-old girl due to
      Staphylococcus aureus infection of an umbilical arterial catheter inserted at
      birth. After resection-anastomosis of the iliac artery the postoperative course
      was uneventful and hemodynamic data remain normal at 2 years. A review of the
      literature indicates that the prognosis of infective aortoiliac aneurysm is poor
      in children, except when the aneurysm is located solely in the iliac artery.
      Arterial continuity should be restored as late as possible after infection using
      a technique consistent with normal growth of the artery in the child.

PMID- 7811590
TI  - Heparin-related thrombocytopenia and adrenal hemorrhagic necrosis following
      aortic surgery.
AB  - Adrenal hemorrhagic necrosis is one of several possible complications of heparin
      related thrombocytopenia. We report a case in which adrenal hemorrhagic necrosis
      developed after aortofemoral bypass. This serious complication remains difficult
      to diagnose in the absence of a high index of suspicion. A routine search for
      this condition in the setting of heparin-related thrombocytopenia is essential
      since a favorable outcome is dependent on early diagnosis.

PMID- 7811591
TI  - Raynaud's Syndrome.

PMID- 7811593
TI  - World malaria situation in 1992. Part III.

PMID- 7811592
TI  - Alternative approaches to the deep femoral, popliteal, and infrapopliteal
      arteries in the leg and foot: Part I.

PMID- 7811594
TI  - Expanded programme on immunization. Rubella outbreak.

PMID- 7811595
TI  - Cholera: unjustified control measures.

PMID- 7811596
TI  - Expanded Programme on Immunization (EPI). Emerging polio-free zone in southern
      Africa.

PMID- 7811597
TI  - In memoriam Professor Ugur Derman, MD, April 24, 1939, to September 4, 1994.

PMID- 7811598
TI  - U.S. Federal Government attempts to promote primary care training.
AB  - The federal government of the United States is concerned that only 30-33% of
      physicians are in primary care practice and not more than approximately 15-20% of
      recent medical graduates choose primary care. Moreover, the distribution of
      interns and residents in primary care in recent years is 40% and after
      "branching" it is realistically only 25%. The federal government's goal through
      legislative intervention is to increase the pool of U.S. medical graduates to
      enter primary care from the current level to at least 50% by the turn of the
      century. To attain this goal, the government is depending on health care reform
      legislation and making changes in federal legislation that reimburses graduate
      medical education through direct and indirect Medicare payments. The federal
      government hopes to produce incentives to increase the pool of primary care
      physicians and to place disincentives on subspecialty training by altering direct
      and indirect Medicare payments in favor of primary care training programs; by
      limiting residency and fellowship slots; and by removing limits on direct
      payments at ambulatory care sites for training, including non-hospital settings.
      There is concern among medical educators that these changes in current
      legislative interventions will not increase to 50% the numbers of medical
      graduates choosing primary care careers. Accredited residency and fellowship
      programs need to assess projected manpower needs immediately to justify their
      positions for achieving a balanced physician workforce for the twenty-first
      century.

PMID- 7811600
TI  - Pediatric oncologists' assessment of oncology education in U.S. medical schools:
      Cancer Education Survey II.
AB  - The status of cancer education in U.S. medical schools was reassessed in the
      Cancer Education Survey II, which was initiated in 1989. One thousand and thirty
      five cancer educators from 126 of the country's 128 medical schools participated,
      including 65 pediatric oncologists and 36 family physicians. All agreed that the
      most important aspects of cancer to teach medical students are early detection
      and cancer prevention; they considered less important electives in basic science,
      radiation therapy, and surgical oncology. The 101 pediatric oncologists and
      family physicians believed that more curriculum time should be devoted to cancer
      epidemiology, psychosocial aspects, and palliative care. Approximately one third
      of these 101 physicians also expressed the desire to have more teaching materials
      available in five general areas: patient education about pediatric cancer,
      nutrition, epidemiology, palliative care, and continuing care. Lay-language
      information about pediatric cancer, participation in clinical trials, and current
      cancer research is still needed.

PMID- 7811599
TI  - Oncology education and cancer prevention in a high-risk region of Russia.
AB  - A part of the Altai Territory of Russia has been subjected to radioactive
      contamination from nuclear testing. Cancer morbidity in neighboring areas has
      increased 15-27%. An anticancer program begun in 1993 is in the developmental
      stage. In conjunction with a number of social measures, a significant education
      program is being developed. It includes, first, education of health care
      professionals in the prevention and early diagnosis of cancer, and second, public
      cancer education. For this purpose it has been necessary to develop teaching
      programs for doctors and other health care professionals (undergraduate and
      postgraduate), schoolteachers and schoolchildren, administrators, members of the
      working classes, and clergy. Because the population has already been subjected to
      a dangerous radiation load, the program for health care professionals is designed
      to eliminate whenever possible the need for radiographic and isotope
      investigations for screening purposes and diagnosis. The public cancer education
      program includes data about the importance of healthy lifestyles and skills for
      self-examination. The authors invite the collaboration of colleagues in other
      countries who have had experience with regional cancer education programs.

PMID- 7811601
TI  - Provision of cancer control services to Native Americans by state health
      departments.
AB  - To examine the extent of cancer prevention and control programs for American
      Indian and Alaska Native (AI/AN) tribal groups directly supported by state public
      health agencies, a cross-sectional survey was completed by chronic disease
      directors in 50 states. Descriptive statistics were used to summarize responses.
      Sixteen states (32%) reported having sponsored/directly supported cancer
      prevention and cancer control services specifically targeted to AI/AN
      populations. Few state public health agencies had developed culturally-relevant
      cancer education materials for AI/ANs. Although the respondents directed chronic
      disease or cancer prevention/control programs in their states, many were
      unfamiliar with cancer patterns or general health problems among AI/ANs. Survey
      results indicate that cancer prevention and control services are available to
      AI/AN populations through most state public health agencies. It is hoped that
      dissemination of survey results will increase awareness of cancer as a health
      problem among AI/ANs and lead to an expansion of the services available to this
      "invisible minority" to levels accessible by the majority population.

PMID- 7811602
TI  - Redesigning the surgical teaching of fourth-year medical students to meet the
      training needs of generalists.
AB  - The fourth year of the medical student curriculum remains of questionable
      educational value at most medical schools. The training needs of generalists
      include the acquisition of knowledge and skills in broad areas of general surgery
      and the surgical subspecialties. By appropriately tailoring the educational
      objectives to the learning needs of individual students and implementing teaching
      models based on principles of adult education, a special surgical experience may
      be provided to each fourth-year medical student, building on the previously
      acquired knowledge and skills. Rotations may be offered in a number of surgical
      disciplines, with heavy emphasis on teaching in the ambulatory setting. One such
      model was recently implemented at The Medical College of Pennsylvania. Advantages
      of this type of program include support of the training of generalists using
      contemporary teaching strategies and provision of a meaningful educational
      experience to medical students during the fourth year.

PMID- 7811603
TI  - Oral cancer education and HIV-associated malignancies.
AB  - Interest and participation in "oral cancer" education courses has been
      disappointingly low, probably because of the sparsity and low impact of cases of
      oral cancer relative to clinical practice. Interest and participation increase as
      subject matter relevant to clinical practice is included to create innovative
      programs. Such subject matter has included more coverage of premalignant lesions
      (leukoplakia and erythroplakia), the role of vital staining (toluidine blue) to
      aid clinical judgment and biopsy, and utilization of lasers for control. A
      significant stimulus to encourage enrollment has been the incorporation of AIDS
      updating and HIV-associated malignancies, which adds identification, curiosity,
      and interest relative to a well-known and very current health care problem. The
      greater course participation presents the opportunity to emphasize the importance
      of oral cancer and clinician roles in prevention, early detection, and
      management.

PMID- 7811605
TI  - Psychosocial adjustment of five-year survivors of childhood cancer.
AB  - This study assessed the psychosocial adjustment of 31 childhood cancer patients
      five years after diagnosis compared with their school peers. The children were
      aged 8 to 18 years at the time of the study. No significant difference was found
      in self-rated measures of anxiety and self-esteem. However, there were
      significant differences in teacher ratings of concentration, academic progress,
      and popularity with peers and in parent and teacher ratings of behavioural
      adjustment (Rutter Scales A and B), indicating that the survivors of childhood
      cancer were at increased risk of problems. Relationships between behavioural
      adjustment scores and child, family, and illness variables were investigated
      within the cancer-survivor group. No significant relationship was found with
      illness variables or social class. Significant associations were found between
      behavioural adjustment and parental psychological distress, parental coping
      strategies, children's perceptions of their own scholastic competence, and their
      relationships with peers. In addition, children who had shown considerable
      problems in school work one year after diagnosis were more at risk for
      behavioural problems at this later state. The findings have implications for the
      provision of support to childhood cancer patients, their families, and their
      teachers that may help to prevent later problems in adjustment.

PMID- 7811604
TI  - "Sunshine and skin health": a curriculum for skin cancer prevention education.
AB  - Skin cancer rates are increasing. Instilling preventive behavior in youngsters is
      essential to prevent overexposure during childhood. The effectiveness of a
      curriculum for increasing knowledge and skills, creating supportive attitudes,
      and engendering a supportive environment to enhance skin cancer prevention was
      tested on 139 fourth-, fifth-, and sixth-graders. One class in each grade was
      assigned to treatment (curriculum) and another to control. The curriculum
      increased knowledge of the effects of exposure to sunlight, skin cancer, and
      prevention immediately and eight weeks later, across all grades. It also
      cultivated less favorable attitudes toward tanning and, among fourth-graders,
      reduced unfavorable attitudes toward sunscreen. Behavioral changes were less
      consistently evident, with students reporting less suntanning, fourth-graders
      more frequently using sunscreen, and fifth- and sixth-graders more frequently
      wearing protective clothing compared with controls. The curriculum was more
      effective at influencing knowledge and attitudes than changing behavior,
      highlighting the need for student- and parent-oriented cues to action.

PMID- 7811606
TI  - The teaching of medical ethics in oncology education.
AB  - The teaching of medical ethics is an important aspect of oncology education. To
      prepare future physicians to cope with the many and complex ethical issues in the
      care of oncology patients, Dartmouth Medical School developed a two-hour medical
      ethics component in the required second-year course on the principles of
      oncology. The paper describes the goals and case method for the teaching of
      ethics.

PMID- 7811607
TI  - Concerned citizens collect cancer-incidence data.
AB  - A method for collecting cancer-incidence data in a rural town is described. A
      mail survey, prompted and conducted by concerned citizens, was utilized. When
      analyzed in light of local mortality data and national cancer incidence and
      mortality rates, the data collected in such a survey seem reasonably accurate and
      complete. The numbers of observed and expected incident cases, as well as the
      numbers of observed and expected deaths, correlated quite closely for most sites.
      Excesses of incident cases were observed for seven of 11 sex-specific sites, but
      only for melanoma and lymphoma among women were the excesses statistically
      significant. Provided that community support is substantial, which is necessary
      to maximize accuracy and completeness, this method of collecting cancer-incidence
      data may be useful in rural areas of states without a statewide registry.

PMID- 7811608
TI  - Quantitative magnetic resonance flow imaging.
AB  - Time-of-flight and phase shift methods have both been used for vascular imaging
      with magnetic resonance. Phase methods, and phase contrast in particular, are
      well suited to quantitative measurements of velocity and volume flow rate. The
      most robust methods for measuring flow encode through-plane velocity into phase
      shift and compute flow by integrating the measured velocity over the vessel
      lumen. The accuracy of the flow data can be degraded by the effects of
      acceleration and eddy currents and by partial volume effects, including the
      effects of finite slice thickness and resolution, pulsatile waveforms, motion,
      and chemical shift. The reproducibility depends on the signal-to-noise of the
      data and the strength of the flow encoding and can be degraded by inconsistent
      definition of the vessel boundary. The adjustable flow sensitivity inherent in
      this method is a particular asset, allowing phase contrast flow measurement to
      operate over a dynamic range exceeding 10(5). Recently developed rapid imaging
      methods are helpful in applications that would be compromised by respiratory
      motion. With care, excellent quantitative data can be quickly obtained in vivo,
      and the resulting flow information is valuable for the diagnosis and management
      of a variety of conditions.

PMID- 7811609
TI  - Magnetic resonance angiography.
AB  - Magnetic resonance (MR) angiography is a broad and expanding field. The
      technology of MR angiograms is evolving to produce higher spatial resolution,
      faster acquisition times, and reduced artifact. Rather than a straight, linear
      evolution, this progress is going forward in a number of areas inherent to the MR
      imaging process. Considerable progress has been demonstrated in such diverse
      areas as flow-sensitized radiofrequency pulses, reduced background signal with
      off-resonance pulses, improved vessel depiction with reduced echo times via
      improved hardware and reconstruction techniques, and improved display with more
      powerful computer algorithms. This review is a brief survey and comparison of
      available techniques for the visualization of blood vessels within the human
      body.

PMID- 7811610
TI  - MRI of degenerative disease of the lumbar spine.
AB  - Low back pain (LBP) is one of the most common reasons that patients seek medical
      attention. Although acute LBP is generally a self-limiting condition, the
      estimated cost for this health care problem exceeds $8 billion annually. MR
      accurately depicts both the morphologic as well as biochemical sequelae of disc
      degeneration. Additionally, MR is superior in its ability to depict disease
      processes that can present in an indistinguishable fashion. Although multiple
      mechanisms have been proposed for the possible etiology of disc degeneration, it
      remains incompletely understood at this time. In addition to the unknown etiology
      of disc degeneration, the relationship between degenerative disc disease and LBP
      has not been firmly established. Substantial percentages of people without a
      history of LBP or sciatica have been shown to have abnormal imaging examinations.
      Mechanical compression of neural elements by disc herniation, as well as direct
      biochemical and inflammatory effects of the contents of the nucleus pulposus upon
      neural structures, have been proposed as possible sources of LBP. Due to the
      above, caution is urged before attributing a particular anatomic finding as the
      patient's source of low back pain.

PMID- 7811611
TI  - Increased fears of HIV and bovine TB link. Interview by Dina Leifer.

PMID- 7811612
TI  - HIV mortality linked to income.

PMID- 7811613
TI  - Right to nurse. In the balance.

PMID- 7811614
TI  - Right to nurse. The human factor.

PMID- 7811615
TI  - A nurse-led service.

PMID- 7811616
TI  - Collaboration among health professionals.
AB  - The benefits to patients of health professionals working harmoniously together
      are almost too obvious to state, so why is there so much contention between
      nurses, doctors and other staff? The author explores some of the reasons behind
      this tension, and suggests some means of overcoming them.

PMID- 7811617
TI  - Drugs used to lower high lipid levels.
AB  - As part of our occasional series highlighting advances in drug therapy, this
      article discusses the mechanisms of hyperlipidaemia and the main groups of drugs
      used to treat the condition including bile acid-binding agents, fibrates,
      nicotinic acid and its derivatives, statins and fish oils.

PMID- 7811619
TI  - Managers: bird brained.

PMID- 7811618
TI  - NHS market reforms: lessons from the US.
AB  - Since their inception, the reforms of the National Health Service have been
      described by some commentators as having great similarities with the kind of
      healthcare services offered in the US. With the assistance of a Fulbright
      Scholarship, the author visited the US in 1993 to study the services offered
      there. This article contains some of her impressions, and spells out the
      potential healthcare similarities between the US and the UK.

PMID- 7811620
TI  - Assisted ventilation. 1: Methods and observation (continuing education credit).

PMID- 7811621
TI  - Tissue Viability Society. Setting up a nurse-led clinic in wound healing.

PMID- 7811622
TI  - Tissue Viability Society. Exploring the role of the tissue viability specialist
      nurse.

PMID- 7811623
TI  - HVA launches new guidance booklet on AIDS and HIV.

PMID- 7811624
TI  - Right to nurse. A job well done.

PMID- 7811625
TI  - The patient's agenda.

PMID- 7811626
TI  - Night nursing. Understanding the nature of sleep.
AB  - This is the first article in a series of three looking at patients' sleep in
      hospitals. This article explores the nature of sleep and reviews the various
      theories that have been put forward to explain why we need to sleep. The other
      two articles will concentrate on sleep disorders and hospitalisation, and the
      role of the night nurse.

PMID- 7811627
TI  - Counselling practice: a questionnaire study.
AB  - A study was carried out to establish an understanding of what the term
      'counselling' meant to a sample of 150 qualified psychiatric nurses working in a
      maximum security special hospital. There appeared to be a lack of understanding
      of the term, with very little supervision of the counselling work nurses
      undertook, and insufficient training to help nurses improve their knowledge of
      the subject. The authors call for proper supervision, further research into staff
      training needs, and more courses and propose that nurses involved in counselling
      should have no ward managerial responsibility for the patients being counselled.

PMID- 7811628
TI  - Pension provision for staff in the NHS.
AB  - Changes in the health service and employment patterns are likely to affect
      pension provision in the future. As the principle of 'a job for life' for
      National Health Service staff becomes less tenable and the large numbers of
      nurses recruited in the Seventies and Eighties reach retirement age, the ease of
      transferring pensions will become increasingly important.

PMID- 7811629
TI  - Learning disabilities: the helping hand of God.

PMID- 7811630
TI  - Women's issues: fashion victim.

PMID- 7811631
TI  - Doctor's HIV comments 'insensitive' say nurses.

PMID- 7811632
TI  - Aromatherapy: the essentials (continuing education credit).

PMID- 7811633
TI  - Perceived locus of causality, goal orientations, and perceived competence in
      school physical education classes.
AB  - Ryan & Connell (1989) have demonstrated that different types of behavioural
      regulation can be located on a continuum of perceived autonomy or perceived locus
      of causality. The present study applied their formulation in the context of
      school physical education (PE) and examined the relationships of perceived
      autonomy, perceived competence and goal orientations with intrinsic interest
      across two PE activities. School students aged 12-14 years (N = 85) completed an
      adapted version of the Self-Regulation Questionnaire (Ryan & Connell, 1989) and
      measures of perceived competence and intrinsic interest separately for two PE
      activities. They also completed the British version of the Task and Ego
      Orientation in Sport Questionnaire (Duda, Fox, Biddle & Armstrong, 1992).
      Students appeared to be differentially motivated for the two activities due to
      different perceptions of autonomy. Structural equation modelling analysis showed
      that perceived autonomy and task orientation had direct effects on intrinsic
      interest for both the activities. Perceived competence, however, was positively
      associated with intrinsic interest only for one of the activities. The
      implications of the results for the practice of physical education are discussed.

PMID- 7811634
TI  - Perceived self-efficacy, social comparison, affective reactions and academic
      performance.
AB  - The present study is based on Bandura's theory of perceived self-efficacy and on
      Wills' theory of downward comparison. We expected that perceived self-efficacy
      and downward comparison, separately and in combination, would contribute to the
      positive feelings of university students regarding their skills and by way of
      these feelings to their study performance. The results largely support this
      expectation. Both perceived self-efficacy and downward comparison contributed to
      the positive feelings of the students. These feelings also influenced their
      course grades. In contrast with the expectation the interaction between self
      efficacy and direction of comparison did not contribute to feelings of students
      regarding their own skills.

PMID- 7811635
TI  - The role of the cAMP pathway in mediating the effect of head activator on nerve
      cell determination and differentiation in hydra.
AB  - In hydra, head activator (HA) acts as positive signal for nerve-cell
      determination and differentiation. For both events, HA uses cAMP as the second
      messenger. Evidence is presented that the cAMP agonist, Sp-cAMPS, is able to
      mimick the effect of HA on nerve-cell determination and differentiation and that
      it is blocked by the antagonist Rp-cAMP. An adenylyl cyclase associated protein,
      CAP, appears to be involved as mediator for transducing the signal from the
      transmembrane HA receptor to the cAMP system. A cDNA coding for hydra CAP was
      isolated from the multiheaded mutant of Chlorohydra viridissima. The hydra CAP
      shows extensive homology with the yeast and, more so, mammalian CAPs. In hydra,
      CAP mRNA is expressed abundantly in interstitial and epithelial cells. The effect
      of HA, but not of cAMP, on nerve-cell differentiation was inhibited by
      pretreatment of hydra with a cap antisense oligonucleotide, suggesting a role for
      CAP as mediator in the signal transduction cascade between HA and cAMP.

PMID- 7811636
TI  - Developmental expression of PC3 gene is correlated with neuronal cell birthday.
AB  - We examined the developmental expression of PC3, a nerve growth factor (NGF)
      early induced gene in PC12 cells, in the rat central nervous system (CNS) and we
      found that it represents a molecular marker of ongoing postmitotic neurons
      production. PC3 is initially expressed in the ventral quarter of the neural tube,
      at the level of the presumptive cervical spinal cord just where and when (10-11
      days post coitum (dpc)) the motor neurons are arising. Subsequently, the
      appearance of PC3 expression follows a ventro-dorsal and a rostro-caudal gradient
      in the spinal cord and a caudo-rostral gradient across the brain vesicles that
      coincide, both spatially and temporally, with the gradients of neurogenesis
      described in the literature. As in PC12 cells, PC3 mRNA expression appears to be
      transient in vivo. In all regions of the CNS, it is restricted to the ventricular
      zone of the neuroepithelium, while neuronal precursors cease to express PC3 as
      they migrate to the mantle zone. Moreover, PC3 mRNA disappears from the various
      regions of the CNS as neurogenesis ceases.

PMID- 7811637
TI  - Dissection of the Drosophila paired protein: functional requirements for
      conserved motifs.
AB  - The Drosophila paired gene encodes three conserved motifs: a homeodomain, paired
      domain and PRD (his/pro) repeat. To investigate the functional importance of the
      PRD repeat and paired domain, we tested deletion mutants using an ectopic
      expression assay in embryos. Our results suggest that the PRD repeat is not
      required for the in vivo regulation of the target genes, engrailed and
      gooseberry. However, the PRD repeat appears to be embedded within a proline-rich
      transcriptional activation domain required for the regulation of these genes. Our
      analysis of the paired domain indicated that its N-terminal half, which is
      required for DNA binding in vitro, is also required for in vivo function, whereas
      surprisingly, the C-terminal half is dispensable for the regulation of engrailed
      and gooseberry.

PMID- 7811638
TI  - Molecular characterization of ovarian tumors in Drosophila.
AB  - Certain female-sterile mutations in Drosophila result in the uncontrolled
      proliferation of X/X germ cells. It has been proposed that this ovarian tumor
      phenotype results from the sexual transformation of X/X germ cells to a male
      identity. We present findings inconsistent with this model. We demonstrate that
      the tumorous cells produced by mutations in the ovarian tumor (otu), Sex-lethal
      (Sxl) and sans fille (snf) genes are capable of female-specific transcription and
      RNA processing. This indicates that these ovarian tumor cells still retain some
      female identity. Therefore, we propose that mutations in these genes do not cause
      a male transformation of the X/X germ line but instead either cause an ambiguous
      sexual identity or block specific stages of oogenesis. Our findings indicate that
      while Sxl is the master sex determination gene in somatic cells, it appears to
      play a more subsidiary role in the germ line. Finally, we demonstrate that the
      germ line function of Sxl depends on the activity of a specific OTU isoform.

PMID- 7811640
TI  - Mouse homeobox gene Dbx: sequence, gene structure and expression pattern during
      mid-gestation.
AB  - Homeobox genes regulate multiple aspects of mouse development including the axial
      patterning in the central nervous system. Some of the more divergent members of
      this gene family are expressed in the anterior region of the central nervous
      system where the Hox genes are not expressed. We previously reported the
      isolation of a mouse homeobox gene, Dbx, from the forebrain. Here we describe its
      genomic structure, complete cDNA sequence, characterization of the basal promoter
      and the expression pattern at different stages of the developing embryo. During
      early and mid-gestation, Dbx expression is restricted to the telencephalon,
      diencephalon, dorsal mesencephalon and spinal cord. At later gestational stages,
      Dbx expression continues in the dorsal mesencephalon and diencephalon, in which
      expression is more restricted than at the earlier stages. Dbx transcripts were
      also detected in the primitive cerebellum. At all stages, the Dbx expressing
      regions contain a high proportion of proliferating cells, suggesting a role for
      Dbx in patterning the central nervous system during embryogenesis.

PMID- 7811639
TI  - Complexity and organization of DNA-protein interactions in the 5'-regulatory
      region of an endoderm-specific marker gene in the sea urchin embryo.
AB  - This study concerns the organization of sites of specific DNA/protein interaction
      within the regulatory domain of the Endo16 gene of Strongylocentrotus purpuratus.
      Earlier work had displayed a complex pattern of expression of this gene during
      embryogenesis. Endo16 transcripts are confined to the definitive vegetal plate in
      blastula stage embryos; at gastrula stage this gene is expressed throughout the
      archenteron, but later only in the midgut. In this work we exploited the
      exceptional experimental accessibility of the sea urchin embryo, with respect to
      both functional assays of gene regulatory systems and to characterization of
      transcription factors, in order to approach a complete description of potential
      Endo16 regulatory interactions. Accurate expression of an Endo16 fusion gene was
      obtained with a 2200-nucleotide (nt) upstream fragment of the gene. We present a
      map locating high specificity target sites for DNA-binding proteins within the
      2200-nt Endo16 regulatory domain, and an assessment of the complexity of the set
      of putative Endo16 transcription factors that we have been able to recover from
      24-h (blastula stage) nuclear extract. Protein binding sites were initially
      mapped by gel shift reactions carried out on nested sets of end-labeled
      restriction fragments, and then to finer resolution by oligonucleotide gel shift
      competitions. Thirty-eight sites of high specificity DNA-protein interaction were
      thus identified. Appropriate oligonucleotides were then used for partial
      purification of the DNA-binding proteins by affinity chromatography. DNA-binding
      proteins specific for each target site were identified by molecular weight, using
      southwestern blotting procedures and two-dimensional gel shift separations, and
      by directly renaturing and reacting with oligonucleotide probes specific proteins
      that had been resolved by SDS-PAGE from selected affinity column fractions. A
      complete series of gel shift cross-competitions amongst the target sites was
      carried out. We conclude that nine different protein factors are bound at unique
      sites within the Endo16 regulatory domain. Multiple target sites for five other
      proteins account for the remaining binding site locations. The target sites
      appear to be organized in a sequence of clusters, focused on the unique factors.
      The high complexity of the Endo16 gene regulatory system may be characteristic
      for genes that are spatially regulated in early embryonic development.

PMID- 7811641
TI  - Localized measures for nonstationary time-series of physiological data.
AB  - We will discuss localized measures related to the concepts of dimension,
      Lyapunove exponents (entropy), and recurrence diagrams. We stress the relevance
      of localized events and coincidences in physiological time series that often are
      lost when statistical averaging methods are applied. We suggest event-based
      statistics as an alternative to spectral or averaged-based statistics. The use of
      wavelets bases for characterizing localized structures is discussed as a
      potential alternative to Fourier-based analysis. Finally we mention how local
      domains in state space could be applied as triggers for external stimuli and
      thereby improve the statistics of ERP recordings.

PMID- 7811642
TI  - Two tools to test time series data for evidence of chaos and/or nonlinearity.
AB  - Two computer programs are described for evaluating the evidence for chaos and
      nonlinearity in time series data. "bx" is an efficient algorithm for computing
      the correlation integral (from which correlation dimension can be estimated); and
      "surrogat" is a Fourier-transform-based algorithm for generating surrogate data
      consistent with a null hypothesis that the data arise as a result of a linear
      stochastic process.

PMID- 7811643
TI  - The point correlation dimension: performance with nonstationary surrogate data
      and noise.
AB  - The dynamics of many biological systems have recently been attributed to low
      dimensional chaos instead of high-dimensional noise, as previously though.
      Because biological data are invariably nonstationary, especially when recorded
      over a long interval, the conventional measures of low-dimensional chaos (e.g.,
      the correlation dimension algorithms) cannot be applied. A new algorithm, the
      point correction dimension (PD2i) was developed to deal with this fundamental
      problem. In this article we describe the details of the algorithm and show that
      the local mean PD2i will accurately track dimension in nonstationary surrogate
      data.

PMID- 7811644
TI  - The fundamentals of controlling chaos.
AB  - The concepts of chaos and its control are reviewed. Both are discussed from an
      experimental as well as a theoretical viewpoint. A detailed exposition of the
      mathematics of chaos control is presented, with an eye toward implementation in
      computer-controlled experiments.

PMID- 7811645
TI  - Discriminating deterministic versus stochastic dynamics in neuronal activity.
AB  - An approach to discriminating deterministic versus stochastic dynamics from
      neuronal data is presented. Direct tests for determinism are emphasized, as well
      as using time series with clear physical correlates measured from small ensembles
      of neurons. Surrogate data are used to provide null hypotheses that the dynamics
      in our data could be accounted for by linear stochastic systems. Algorithms are
      given in full, and the analysis of an experimental example is given.

PMID- 7811646
TI  - Testing the determinism of EEG and MEG.

PMID- 7811647
TI  - Changes of chaoticness in spontaneous EEG/MEG.
AB  - Depending on the task being investigated in EEG/MEG experiments, the
      corresponding signal is more or less ordered. The question still open is how can
      one detect the changes of this order while the tasks performed by the brain vary
      continuously. By applying a static measurement of the fractal dimension or
      Lyapunov exponent, different brain states could be characterized. However,
      transitions between different states may not be detected, especially if the
      moments of transitions are not strictly defined. Here we show how the dynamical
      measure based on the largest local Lyapunov exponent can be applied for the
      detection of the changes of the chaoticity of the brain processes measured in EEG
      and MEG experiments. In this article, we demonstrate an algorithm for computation
      of chaoticity that is especially useful for nonstationary signals. Moreover, we
      introduce the idea that chaoticity is able to detect, locally in time, critical
      jumps (phase-transition-like phenomena) in the human brain, as well as the
      information flow through the cortex.

PMID- 7811648
TI  - Non-equilibrium dynamics as an indispensable characteristic of a healthy
      biological system.
AB  - Healthy systems in physiology and medicine are remarkable for their structural
      variability and dynamical complexity. The concept of fractal growth and form
      offers novel approaches to understanding morphogenesis and function from the
      level of the gene to the organism. For example, scale-invariance and long-range
      power-law correlations are features of non-coding DNA sequences as well as of
      healthy heartbeat dynamics. For cardiac regulation, perturbation of the control
      mechanisms by disease or aging may lead to a breakdown of these long-range
      correlations that normally extend over thousands of heartbeats. Quantification of
      such long-range scaling alterations are providing new approaches to problems
      ranging from molecular evolution to monitoring patients at high risk of sudden
      death. We briefly review recent work from our laboratory concerning the
      application of fractals to two apparently unrelated problems: DNA organization
      and beat-to-beat heart rate variability. We show how the measurement of long
      range power-law correlations may provide new understanding of nucleotide
      organization as well as of the complex fluctuations of the heartbeat under normal
      and pathologic conditions.

PMID- 7811649
TI  - Characterization of state transitions in spatially distributed, chaotic,
      nonlinear, dynamical systems in cerebral cortex.
AB  - The neurons of cerebral cortex are largely autonomous and generate activity that
      is manifested in trains of microscopic axonal action potentials. The neurons
      interact by sparse but numerous synaptic connections to generate macroscopic
      dendritic activity patterns that are observed in electroencephalographic (EEG)
      waves. The macroscopic patterns are constructed by the populations and they shape
      the output of cortical neurons in parallel arrays. Sensory cortexes receive
      sensory information in the form of microscopic action potentials, which induce
      state transitions in population dynamics. Each state transition transforms
      sensory information to perceptual meaning. The EEG reflects both kinds of
      activity. The sensory input is accessed by time ensemble averaging, whereas the
      perceptual output is found by spatial ensemble averaging. Spatial phase gradients
      in the EEG are useful for identifying EEG segments in a sequence of state
      transitions in response to sensory input. The rapidity and flexibility with which
      they take place give strong reason to postulate that the mechanism for the
      construction of these sequences of patterns is a dynamical system operating in a
      chaotic domain.

PMID- 7811650
TI  - The chaos user's tool kit.

PMID- 7811651
TI  - A guide to dynamical analysis.
AB  - The number and variety of methods used in dynamical analysis has increased
      dramatically during the last fifteen years, and the limitations of these methods,
      especially when applied to noisy biological data, are now becoming apparent.
      Their misapplication can easily produce fallacious results. The purpose of this
      introduction is to identify promising new methods and to describe safeguards that
      can be used to protect against false conclusions.

PMID- 7811652
TI  - Chaos in physiology.
AB  - A bird's eye view of the role of nontrivial dynamical phenomena in physiological
      systems is presented. Many levels in the physiological hierarchy are affected. It
      appears that physiology has a particularly high affinity to chaos. The old
      central place of physiology in the circle of sciences can perhaps be regained if
      the two disciplines join resources. Even physics may turn out to be dependent on
      the chaotic micro dynamics of the brain.

PMID- 7811653
TI  - How to institute and develop a strategic marketing plan for your pediatric dental
      office.
AB  - As what may be the most important element in a successful pediatric dental
      practice, marketing is often misunderstood. It requires careful planning and a
      long-term commitment. Before implementing your marketing plan, understand the
      definition of marketing and what it will mean to your practice. To develop your
      plan, ask yourself several important questions that will help you analyze where
      you are now, as well as where you want to be. Then, promote your practice by
      incorporating 12 important qualities into your plan. The plan is the blueprint
      for your efforts to repeatedly, consistently, and positively communicate with
      your market for the long term.

PMID- 7811654
TI  - Periodontal considerations in the treatment of maxillary impacted cuspids.
AB  - Proper diagnosis, surgical management and application of biomechanics have
      paramount clinical significance in order to prevent potential mucogingival
      problems and to ensure the outcome of treatment in cuspid impaction cases.

PMID- 7811655
TI  - Bio-thermal Herbst application during the mixed dentition period.
AB  - As is well known Class II division 1 cases are the most common cases which may be
      treated by functional therapy. The best treatment time is the peak growth period
      for such cases which might coincide with mixed dentition usually. Removable
      functional appliances are used in cooperative patients successfully but they are
      not indicated in noncooperative and mouth-breathing patients. Biothermal Herbst
      appliance is such an appliance which may be used as a fixed appliance in the
      mixed dentition period. The aim of this study was to observe the clinical usage
      and the effectiveness of Biothermal Herbst appliance with four cases in mixed
      dentition. At the end of the treatment period, Class II skeletal and dental
      relationships were transformed to Class I, upper incisors uprighted in all cases
      and lower incisors proclined in whole except one case.

PMID- 7811656
TI  - The sedative effects of intranasal midazolam administration in the dental
      treatment of patients with mental disabilities. Part 2: optimal concentration of
      intranasal midazolam.
AB  - In a previous paper, we reported on the effect of a 0.2 mg/kg dose of midazolam,
      administered intranasally, prior to performing various restorative dental
      procedures on a group of mentally disabled patients under local anesthesia and
      nitrous oxide/oxygen analgesia. The purpose of this study was to compare the
      clinical and possible adverse effect of doses of 0.2 mg/kg and 0.3 mg/kg
      midazolam, administered intranasally, and to determine the most appropriate
      concentration for the drug when administered by this route. Patients were
      assessed by a behavioral test which consisted of a scale from 1-7 with 3 ranges:
      markedly effective (1-3), effective (4-5) or ineffective (6-7). Forty-three
      mentally handicapped patients, aged 5 to 20 years, all of whom had previously
      exhibited highly combative and resistant behavior toward dental treatment under
      local anesthesia, were stratified by age and randomly assigned in a double blind
      manner to two groups, receiving either 0.2 mg/kg or 0.3 mg/kg midazolam
      administered intranasally. Group 1, consisting of 22 patients, average age 11
      years 8 months, received 0.2 mg/kg. Group 2 consisted of 21 patients, average age
      13 years 8 months, each of whom was administered 0.3 mg/kg intranasal midazolam.
      Only patients assessed as ASA anesthesia status I or II were admitted to the
      study. Subsequent to intranasal administration of midazolam, no patient rejected
      the nasal mask nor refused to inhale nitrous oxide/oxygen. The induction of
      nitrous oxide/oxygen sedation and oral examination were effected smoothly in
      every case in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7811657
TI  - Masticatory function in normal and crowded occlusion using Hellman's dental
      stages.
AB  - As a consequence of this study, the following conclusions were obtained by means
      of an estimate of the interocclusal point number of the integrated value of the
      electromyographs, of the masticatory rhythm with 40 subjects in each group (the
      normal groups: IIA 10. IIIA 10, IIIC 10, IVA 10; the crowding groups: IIA 10,
      IIIA 10, III C 10, IVA 10). 1. From the view of the integrated value of the
      electromyographs. In the normal groups with a normal occlusion. TA% to the total
      active potentials turned out to be less in proportion to the advancement of the
      dental stages, while TP% remained as the same. M% should an increase, whose ratio
      turned out to be high enough to take TA's place. 2. In the crowding groups, in
      spite of the indication of TA's decrease, M's increase, a comparison with the
      normal groups' that even after the stage IIIC TA-M-type masticatory pattern had
      to be maintained. 3. Regarding the interocclusal point number, in IIIC, IVA, the
      total amount and number at the molar segments indicated a significantly smaller
      value in the crowding groups. 4. Concerned with the integrated value of the
      masticatory muscle, the most related factor to yield the characteristic
      masticatory pattern observed in the crowding groups could be considered the
      number of the interocclusal points, which proved that great importance should be
      paid to the maintenance of the well harmonized status of the upper and lower
      occlusion.

PMID- 7811658
TI  - Comparison of electrosurgery and formocresol as pulpotomy techniques in dog
      primary teeth.
AB  - The primary teeth of four dogs were treated using either a conventional
      formocresol or electrosurgical technique following pulpotomy. Pulps of the
      treated teeth were evaluated histologically for the presence of inflammation,
      fibrosis, necrosis, resorption, and reparative dentin formation. Results
      indicated that conventional formocresol pulpotomy technique is
      histopathologically superior to electrosurgery pulpotomy technique.

PMID- 7811659
TI  - Dental and craniofacial findings in hypohidrotic ectodermal dysplasia during the
      primary dentition phase.
AB  - A more detailed knowledge of dental and craniofacial features in hypohidrotic
      ectodermal dysplasia (HED) during childhood is needed in order to include these
      characteristics among diagnostic criteria. The present study comprised 5 HED
      children, 4 males and 1 female, during the primary dentition phase. Clinical and
      radiological dental findings consisted of multiple congenitally missing primary
      teeth, conoid primary incisors, moderate to severe taurodontic second primary
      molars. Supernumerary cusps and diastema were found as well. A pattern of
      symmetry was assessed for hypodontia in the primary dentition. The cephalometric
      study compared the HED sample to a matched non-syndrome sample and revealed
      abnormally short maxillary depth (p < 0.05), strongly reduced lower facial height
      (p < 0.01) and a reduction in facial soft tissue thickness (p < 0.05 - p < 0.01)
      in HED children. The importance of an early diagnosis and treatment of HED dento
      facial malformations so as to improve esthetics and function is stressed.

PMID- 7811660
TI  - Cockayne's syndrome: dental findings and management.
AB  - A case report is presented to familiarize the dental practitioners with
      Cockayne's Syndrome (CS), a rare autosomal recessive premature aging syndrome.
      Significant physical and dental findings contributed to a most challenging case
      for the dentist and anesthesiologist.

PMID- 7811661
TI  - Dens invaginatus: complications and treatment of non-vital infected tooth.
AB  - A case of non-vital infected dens invaginatus of the maxillary right lateral
      incisor with open apex, which presented with pain and swelling is presented.
      Although root growth and apical closure was achieved using calcium hydroxide, the
      periapical infection persisted and resolution was only achieved after apical
      curettage and apicectomy.

PMID- 7811662
TI  - Extreme transmigration of mandibular cuspid: report of two cases.
AB  - Transmigration of impacted mandibular cuspid to the opposite side seems
      unhypothetical due to the presence of symphyseal cartilage. Two such rare cases
      of extreme transmigration were radiographically discovered when patient reported
      for orthodontic therapy.

PMID- 7811663
TI  - Major recurrent aphthous stomatitis in an 11-year-old girl: case report.
AB  - A case of major Recurrent Aphthous Stomatitis (RAS) in an 11-year-old girl is
      described to illustrate a disease which is relatively rare in children. The
      patient manifested classic signs of major RAS: painful ulcers, 5-10 millimeters
      in diameter, present on the lower lip, on the free and attached gingiva, and on
      the soft palate, lasting over 6 weeks. Familial tendency was evident. Emotional
      stress is suggested as a possible etiological factor for the occurrence of major
      RAS in this patient. Disappearance of the ulcers occurred after the stress had
      been relieved.

PMID- 7811664
TI  - Patient education and preventive care in Malaysian dental practice.
AB  - A questionnaire survey was conducted to examine the attitudes of Malaysian
      dentists toward patient education and preventive dentistry and the level of
      preventive care adopted in Malaysian dental practice. An adjusted response rate
      of 73.1% was obtained. Generally the Malaysian dentists had positive attitudes
      towards patient education and preventive dentistry including fluoridation.
      However, a sizable proportion of them considered that preventive measures were no
      challenge for the dentist. The common preventive measures given to patients were
      scaling, dental health education, prophylaxis and instruction in correct brushing
      and flossing in as much as 40 to 50 percent of the queried dentist claimed that
      these preventive items were provided to most or all of their new patients. In
      spite of the fact that the majority of the dentists had good knowledge about the
      application and effects of sealants only about 41 percent of the dentists claimed
      to have used sealants. More dentists in the private sector reportedly having done
      so. Also many Malaysian dentists (18.5%) did not use leaded protection for any of
      their new patients when taking radiographs.

PMID- 7811665
TI  - Status report: pediatric oral health.

PMID- 7811666
TI  - Better than no care at all?

PMID- 7811667
TI  - Clinical assessment of glass ionomer/composite resin sealant restorations in
      permanent teeth: results of a field trial after 1 year.
AB  - A large field trial is in progress in the Community Dental Service in the West of
      Scotland to evaluate the effectiveness of glass ionomer/composite resin sealant
      restorations in the treatment of fissure caries. 128 of the restorations were
      placed by 14 community dental officers. After 1 year, 98 restorations were
      reviewed. All of the glass ionomer restorations were retained but only 12 of the
      sealants were completely intact. Sealant was retained over only 32% of the
      restorations and in 13%, 48% and 69% of adjacent buccal, occlusal and palatal
      fissures, respectively.

PMID- 7811668
TI  - Clinical evaluation of a light-cured glass ionomer lining cement.
AB  - This study was a clinical evaluation of a light-cured glass ionomer lining
      material (Fuji Lining LC) applied to prepared cavities in 45 primary teeth of
      children aged 3-5 years. The overall assessment, based on clinical and
      radiographic findings, was 'good' in 42 cases and 'fair' in the other three
      cases. The material had no effect on the shade of the composite resin restorative
      material that was used. The findings indicate that Fuji Lining LC has significant
      value in clinical practice.

PMID- 7811669
TI  - The distribution and severity of tooth wear and the relationship between erosion
      and dietary constituents in a group of children.
AB  - There is very little published information on the severity of tooth wear in
      children. The current investigation involved clinical examination of 101 children
      and an assessment of their dietary habits. Evidence of tooth wear was found in
      over 80% of maxillary incisor teeth, and 30% of primary molar teeth had some
      dentine exposed. There were 21 children who were regarded as having 'mild'
      erosion, 45 'moderate' erosion and 35 'severe' erosion. There were highly
      statistically significant differences between the three groups in relation to
      drinking habits; the mean number of carbonated drinks consumed per week by
      children in the 'mild', 'moderate' and 'severe' erosion groups was 3.9, 5.8 and
      13.9 respectively, of fruit drinks 10.3, 16.4 and 18.3, and of all fruit-based
      drinks 17.9, 27.1 and 39.0. There were also highly significant differences in
      those having a fruit-based drink at bed-time; 14% in the 'mild' erosion group,
      32% in the 'moderate' and 60% in the 'severe' group. Although fresh fruit and
      yoghurt consumption followed the same trend, this did not reveal statistically
      significant differences. It is important to identify children who exhibit
      clinical evidence of erosion so that advice can be given about consumption of
      acidic dietary constituents.

PMID- 7811670
TI  - Periodontal ligament injection in the dog primary dentition: spread of local
      anaesthetic solution.
AB  - The spread of local anaesthetic solution administered with a pressure syringe has
      not been studied as extensively in young animals having primary or mixed
      dentitions as in adult animals. The purpose of this investigation was to study
      the distribution of local anaesthetic solution injected into the periodontal
      ligament of young dogs. India ink was added to carpules containing 2% lidocaine
      and 1:100,000 epinephrine, and the spread of solution was examined
      macroscopically and microscopically. Injections were made with a pressure syringe
      (Ligmaject) at 58 sites mesial and distal to primary teeth in five dogs aged 3-9
      months. Three dogs were killed within 12 hours, the other two after 5 days.
      Spread of the ink was studied in non-decalcified slabs, in three-dimensional
      cleared specimens, and in histological sections. The solution usually reached the
      alveolar bone crest, seeped under the periosteum and alongside vascular channels
      into bone marrow, reaching natural cavities such as the crypts of tooth buds and
      the mandibular canal. The ink did not penetrate into the enamel organ or contact
      the permanent tooth buds. The solution appeared to spread along the path of least
      resistance, governed by the intricacies of anatomical structures and fascial
      planes. Therefore the risk of mechanical damage to permanent tooth germs appears
      to be minimal.

PMID- 7811671
TI  - Factors related to plaque distribution in a group of Canadian preschool children.
AB  - The purpose of this study was to identify factors that were related to plaque
      distribution in a group of preschool children. 153 children aged 3-5 years from
      seven randomly-selected preschool programmes in Saskatoon, Canada, were examined
      for plaque (Silness & Loe, 1964) and for dental caries (WHO, 1987). The subjects
      were divided into three groups according to age: 3, 4 and 5 years old. Plaque was
      assessed on the buccal and lingual surfaces of all teeth. The examinations were
      conducted in the morning or afternoon. No prior oral hygiene instructions were
      given to the children or parents. Teachers, however, were informed when the
      examinations would take place. The mean total plaque score was 0.51. There was no
      significant difference between the plaque scores for the different age groups.
      Total plaque score was significantly related to dft and dfs scores (P < 0.05).
      The mean dft was 0.68 and mean dfs was 1.18, and 80.4% of the subjects were
      caries-free and had no restored teeth or surfaces. There was significantly more
      plaque on posterior teeth than on anterior teeth (P < 0.0001), and on buccal
      surfaces than on lingual surfaces (P < 0.001) in both mandibular and maxillary
      arches. Significant differences in plaque distribution were also found between
      subjects examined in the morning or the afternoon.

PMID- 7811672
TI  - The dental caries experience, oral hygiene and dietary practices of preschool
      children of factory workers in Phnom Penh, Cambodia.
AB  - Two hundred and thirty-seven children attending four Ministry of Industry nursery
      schools in Phnom Penh, Cambodia, were examined. Dental caries experience, oral
      cleanliness and soft tissue abnormalities were determined. 149 mothers of these
      children were interviewed and information was gathered about infant-feeding
      practices, weaning age, diet after weaning, toothbrushing and dental attendance.
      Dental caries experience was high, and only 36% of children aged 1-4 years and 4%
      of those aged 5-6 years were caries free. Only 15% of mothers reported bottle
      feeding, but 70% of these used sweetened canned milk in the bottle. Oral hygiene
      was rated as poor in 80% of children and only 10% were reported to use a
      toothbrush. 43% of children were reported to have experienced toothache, but only
      5% had been to a dentist.

PMID- 7811673
TI  - An unusual radiographic finding.

PMID- 7811674
TI  - Is cleft lip and palate surgery in utero conceivable?

PMID- 7811675
TI  - Oral health care services for Hong Kong children.

PMID- 7811676
TI  - Prenatal care and maternal health during adolescent pregnancy: a review and meta
      analysis.
AB  - PURPOSE: A meta-analysis and review of pregnancy complications and behavioral
      risk factors associated with infant low birth weight and other poor outcomes
      which occur during adolescent pregnancy was undertaken using the published
      literature. METHODS: Studies were eligible for inclusion if they: 1) utilized a
      clearly defined sample of teenagers 2) provided numeric data on complications of
      interest or the proportions needed to compute this information 3) included a
      control or comparison group. RESULTS: Many behavioral risk factors (smoking,
      drinking and drug use) appeared to be less prevalent among teenage gravidas,
      particularly when the young women were ethnic minorities. An increased risk of
      preterm delivery was associated with young maternal age in both developed and
      developing countries. In the developed world, risk of cesarean delivery was
      reduced for teenagers and there was a secular decline in maternal anemia and
      pregnancy induced hypertension in comparison to the risk sustained by more mature
      women. Programs of comprehensive prenatal care appeared to have the potential to
      diminish risk of many complications. In the developing world, teenagers were at
      increased risk of maternal anemia, preterm birth and cesarean delivery.
      CONCLUSIONS: Although future research efforts will need to address the issues of
      bias inherent in much of the published research, the published literature
      suggests that prenatal care regimens which provide social and behavioral services
      along with medical care could improve both the health of the mother and the
      outcome of her pregnancy.

PMID- 7811677
TI  - Outcomes of intensive AIDS education for male adolescent drug users in jail.
AB  - OBJECTIVES: The purpose of the study was to conduct and evaluate an intensive
      AIDS education program for incarcerated male adolescent drug users. METHODS: The
      study was conducted in New York City's main jail facility for detained and
      sentenced male youths aged 16-19 years. A four-session, group-oriented AIDS
      education program based on Problem-Solving Therapy was conducted. The program was
      voluntary and all youths on designated dormitories were invited to participate.
      The evaluation compared youths participating in the AIDS education with waiting
      list controls who were discharged or transferred before they could be offered the
      education. Behavioral outcomes for AIDS education participants and controls were
      determined at a five month follow-up after release from jail. Behaviors were
      measured through personal interviews at baseline and follow-up. RESULTS: High
      rates of HIV risk behaviors were documented, including alcohol, marijuana and
      cocaine/crack use that may predispose youths to sexual risk-taking: practice of
      heterosexual anal sex; multiple and high-risk sexual partnerships; and no, or
      inconsistent, use of condoms. Education participants as compared with controls
      were significantly more likely to increase their condom use, to increase positive
      attitudes towards condoms, and possibly to decrease high-risk sexual
      partnerships. However, other sexual risk variables and substance use were
      unchanged. CONCLUSION: Intensive AIDS education provided in jail can be useful in
      reducing certain HIV risk behaviors of criminally-involved male adolescents.

PMID- 7811678
TI  - Nutrition, dieting, and fitness messages in a magazine for adolescent women, 1970
      1990.
AB  - PURPOSE: This study was designed to characterize nutrition and fitness messages
      presented between 1970-1990 in a magazine for adolescent women; to evaluate
      whether these messages changed over time; and to assess the body shape portrayed
      as desirable, and whether this changed over time. METHODS: A data collection form
      was developed to code nutrition and fitness-related written items, advertisements
      and recipes, and the page coverage allocated to these items. Body shape was
      assessed by measuring bust:waist and hip:waist ratios of photographs of models
      wearing bathing suits or underwear. Magazines from even years between 1970-1990
      (n = 132) were coded. RESULTS: Both nutrition-related and fitness-related
      coverage emphasized weight loss and physical appearance. Half the major nutrition
      related articles presented a weight-loss plan, and weight loss was frequently
      addressed in other nutrition articles. The primary reasons presented for
      following a nutrition of fitness plan were to lose weight and become more
      attractive. Statements that the product or service would promote weight loss were
      found in 47% of nutrition-related advertisements. Nutrition coverage did not
      exhibit a net change over time, whereas fitness coverage increased (F = 6.6, p <
      .005), and the ratio of nutrition: fitness coverage changed from 10:1 in 1970 to
      0.75:1 in 1990. Models' body shapes were less curvaceous than those in magazines
      for adult women, and the hip:waist ratio decreased over time (F = 7.3, p < .01).
      CONCLUSIONS: The nutrition and fitness messages in this magazine for adolescent
      women emphasize body shape and appearance, similar to findings from adult women's
      magazines, and contribute to the cultural milieu in which thinness is an
      expectation for women. Between 1970-1990, the emphasis on fitness increased, and
      the body shape of models tended to become more linear.

PMID- 7811679
TI  - Pediatricians' views of access to health services for adolescents.
AB  - PURPOSE: The American Academy of Pediatrics (AAP) carried out a member survey to
      measure pediatricians' views of parental permission and notification for selected
      health services for two age groups of adolescents, the 13 to 15 year olds and the
      16 to 17 year olds. METHODS: Through an AAP Periodic Survey, a sample of 1000
      members of the AAP were sent questionnaires to fill out and return. The response
      rate was 77%. RESULTS: The majority of pediatricians in all groups examined
      believed parental permission and notification were important for general medical
      and surgical care. But for most other types of care delineated, related to
      substance abuse and sexuality, most pediatricians did not believe parental
      permission should be required, except for requests for abortion for 13-15 year
      olds. For several types of care most pediatricians believed parental notification
      should be required for 13-15 year olds. Older pediatricians, male pediatricians,
      and self-employed pediatricians were more apt to support both parental permission
      and notification for all types of care. When age, gender and self versus not self
      employed were introduced together through a logistic regression procedure
      differences in views were accounted for by self versus not self-employed, and age
      and gender had no additional impact. CONCLUSIONS: Most pediatricians supported
      the right of minors to seek care without parental permission for care related to
      substance abuse and sexuality. The majority were less likely to grant
      confidentiality to adolescents, particularly those 13 to 15 years.

PMID- 7811680
TI  - Characteristics of teens tested for HIV in a metropolitan area.
AB  - PURPOSE: This article describes the status of HIV infection in an adolescent
      population attending publicly supported HIV testing clinics in Houston. METHODS:
      Records were reviewed of 4017 teenagers receiving HIV counseling and testing
      services over a period of three years (January 1990 to December 1992). We
      analyzed demographic characteristics, risk exposure groups, results of HIV
      antibody testing, and post-test counseling return rates. RESULTS: An overall
      seroprevalence rate of 10.2 per 1000 was observed, with the majority of cases
      seen among black females. Forty-nine percent of teens with the virus failed to
      acknowledge a risk factor, but of those who did, male-to-male sexual contact was
      the most frequently reported. None who tested positive reported injected drug
      use. The majority of teens tested never returned to obtain their test results and
      post-test counseling. CONCLUSIONS: In order to reinforce preventive behavior,
      institutional and other barriers should be examined and priority given to
      contacting both seropositive and high-risk clients who have sought testing.
      Interventions that encourage condom use or address sexual behavior may be more
      beneficial to teens than those that simply focus on drug use.

PMID- 7811681
TI  - Emergency department utilization by adolescents.
AB  - PURPOSE: To review adolescents' utilization of a hospital emergency department
      (ED) in a rural area, to identify their characteristics, and to explore their
      motivation to seek health care in this setting. METHODS: A retrospective chart
      survey of all 4932 adolescent visits (ages 12-18 years, 55.5% females) to the ED
      in a small town with a population of 55,000 serving a rural area was conducted
      for the calendar year 1989. Chief complaints and diagnoses were retrospectively
      categorized according to six groups: injury, pulmonary problems, Ob/Gyn,
      infection, nonspecific pain (complaint)/no diagnosis (diagnoses), and "other."
      RESULTS: There was an increasing number of visits with increasing age.
      Adolescents with private insurance, who accounted for 50% of patients, were more
      likely than self-paying adolescents (14%) and adolescents on Medicaid (36%) to
      have a primary care source and to have access to a telephone. Injury was the most
      common diagnosis with motor vehicle accidents (MVA) accounting for 15% of all
      injuries. Self-paying adolescents and those on Medicaid were more likely to be
      diagnosed with an infection or an Ob/Gyn problem than adolescents with health
      insurance. Only 5.9% of adolescents were admitted to the hospital service. 8.5%
      of adolescents were discharged from the ED without a diagnosis. 78% of these had
      complained about nonspecific pain. CONCLUSIONS: Many adolescents in this rural
      area were found not to have an identified primary care source and to seek health
      care in EDs. Illnesses that could have been prevented or treated in a more cost
      effective setting thus become "emergencies." Primary care sources are needed that
      are accessible and acceptable to adolescents.

PMID- 7811683
TI  - Self-reported use of drugs for sleep or distress among French adolescents.
AB  - PURPOSE: In the framework of an epidemiological survey on adolescent health, we
      investigated teenagers' psychotropic drug use to identify risk factors. METHODS:
      A representative sample of school adolescents aged 12-20 years (N = 3287) was
      asked to fill out a self-administered questionnaire on their current health
      status (depressive mood, somatic complaints) and their psychotropic drug use.
      Parents completed a second questionnaire about the subjects' childhood. RESULTS:
      About one in five (21.1%) indicated having used psychotropic medications during
      the previous 12 months, most of which were prescription drugs. Drugs for tension
      or distress were taken more frequently than ones for sleep disorders.
      Psychotropic drug use was more widespread among girls (27.5%) than among boys
      (13.8%), and it increased with age: at 18 years 27.9% of the teenagers (versus
      12.7% at age 12-13 years) had used psychotropic medicine. Adolescent psychotropic
      drug use was related to current depressive mood or somatic complaints, and to
      consumption of psychotropic drugs during childhood. A logistic regression
      analysis showed that current depression and past psychotropic use between the
      ages of 6-12 years were the major associated factors of adolescent consumption.
      CONCLUSIONS: The hypothesis of psychotropic drug use as an early "learned"
      response to psychological problems is discussed.

PMID- 7811682
TI  - Adolescent pregnancy and subsequent obesity in African-American girls.
AB  - PURPOSE: Obesity is a significant contemporary health problem among African
      American women. This study investigates whether excessive gestational weight gain
      during adolescent pregnancy is associated with subsequent obesity. METHODS:
      Thirty previously pregnant African-American adolescents on whom there were
      extensive extant anthropometric and psychosocial data were evaluated
      approximately 3.3 years following delivery. RESULTS: Rapid gestational weight
      gain (> .40 kg/wk) was associated with a 19.9% increase in body mass index (BMI);
      average gestational weight gain (.23 to .40 kg/wk) was associated with a 13.2%
      increase, and slow gestational weight gain (< .23 kg/wk) was associated with a
      3.4% increase (difference between rapid and slow, p < 0.05). Adolescents who had
      high prepregnant BMIs were massively obese subsequently. CONCLUSIONS: 1. Rapid
      gestational weight gain is associated with a significantly greater percent change
      in the BMI compared with the slow gestational weight gain in adolescent
      pregnancy. 2. Adolescents who are obese prior to their first pregnancy often
      become even more obese on average 3.3 years following pregnancy. Such adolescents
      may be at particular risk of retaining gestational weight gain, and the
      consequences of their morbid obesity may be ultimately life-threatening.

PMID- 7811684
TI  - Determinants of condom use by Australian secondary school students.
AB  - PURPOSE: To identify factors that are associated with condom use to aid in the
      understanding of how to change the behavior of those young people who have sex
      without using condoms. METHODS: The article reports data from 932 sexually active
      grade 10-12 students from a sample of 72 public secondary schools in seven
      Australian states and territories. The data were collected using a cross
      sectional, self-report questionnaire. RESULTS: Boys were more likely than girls
      to report that a condom was used the last time they had sex. For boys and girls,
      communication with a partner about avoiding infection with HIV/STDs, the belief
      that more peers use condoms, and a higher perceived risk of becoming infected
      with HIV/STDs were associated with using a condom, as was lower knowledge of
      STDs. The use of oral contraception and the unavailability of condoms were
      reported by the students as prominent reasons for non-use of condoms. Number of
      sexual partners in the past year and type of relationship with partner on the
      most recent occasion were not associated with condom use. CONCLUSIONS:
      Adolescents are more concerned with unwanted pregnancy than with disease
      prevention. School students more at risk are not more likely to take the
      necessary precautions to protect themselves from HIV/STDs.

PMID- 7811685
TI  - Protein fluorescence, dynamics and function: exploration of analogy between
      electronically excited and biocatalytic transition states.
AB  - With the advent and development of time-resolved spectroscopic techniques and
      substantial progress in understanding of photophysical and photochemical
      phenomena, a new goal may be achieved: modeling of biochemical reaction or its
      elementary step by a photochemical event occurring within the probe, bound to a
      protein molecule. The probe may be located in a well-determined site of the
      protein matrix and report on the modulation of the reaction rate by the matrix
      and by the surrounding solvent, or by interactions in multiprotein complexes and
      in biomembranes. The advantages of this approach are obvious: in contrast to
      ordinary biochemical reaction, the excited-state reaction may be started by a
      short light pulse, and its kinetics may be observed directly with high resolution
      in time. In addition, if the reaction rate is influenced by the dynamics of the
      protein matrix, these dynamics may be studied simultaneously with the reaction,
      by using the same or a similar probe and within the same time range. In this
      review, the prospects for application of probes exhibiting electron transfer,
      proton transfer, molecular rotations and isomerizations are presented and
      discussed. The general problem of photochemical modeling of biochemical reactions
      is discussed. This modeling may result in deeper understanding of enzyme
      catalyzed reaction mechanisms.

PMID- 7811686
TI  - Expression, purification, and characterization of the Kunitz-type proteinase
      inhibitor domain of the amyloid beta-protein precursor-like protein-2.
AB  - In this report we describe the use of the methylotrophic industrial yeast Pichia
      pastoris as a host system for the large scale production of the Kunitz-type
      proteinase inhibitor (KPI) domain of the amyloid beta-protein precursor-like
      protein-2 (APLP-2). The expression plasmid for the KPI domain of APLP-2 encoded
      amino acids 305-364 of the APLP-2 cDNA (Slunt et al. (1994) J. Biol. Chem. 269,
      2637-2644). The secreted 60 amino-acid product was purified to homogeneity and
      biochemically characterized. Amino-acid sequencing of the expressed KPI domain of
      APLP-2 verified its integrity. The proteinase inhibitory properties of the KPI
      domain of APLP-2 were compared to those of the KPI domain of proteinase nexin
      2/amyloid beta-protein precursor (PN-2/A beta PP). Both KPI domains potently
      inhibited trypsin and, to a lesser extent, chymotrypsin, plasmin, and coagulation
      factors XIa and IXa. However, the KPI domain of APLP-2 was a approximately 20
      fold less effective inhibitor of coagulation factor XIa compared to the KPI
      domain of PN-2/A beta PP. Similarly, the KPI domain of APLP-2 was a less
      effective anticoagulant in coagulation based assays than the KPI domain of PN-2/A
      beta PP. These studies indicate that the KPI domains of PN-2/A beta PP and APLP-2
      form a family of proteinase inhibitors although the former is a better inhibitor
      of factor XIa and a more potent anticoagulant than the latter.

PMID- 7811687
TI  - Creatine kinase compactness and thiol accessibility during sodium dodecyl sulfate
      denaturation estimated by resonance energy transfer and 2-nitro-5
      thiocyanobenzoic acid cleavage.
AB  - We have investigated the effect of increasing sodium dodecyl sulfate (SDS)
      concentrations on rabbit muscle cytosolic creatine kinase structure by two
      methods. We have first determined the variation of accessibility of the thiol
      groups of the enzyme during SDS denaturation by a technique which involves an
      irreversible chemical modification of CK accessible thiol groups, followed by
      NTCB cleavage before the unmodified cysteines in 8 M urea (pH 9) and analysis of
      the peptides obtained by resolutive gel electrophoresis, without sequencing. We
      have determined that the order of accessibility of CK MM cysteine residues during
      SDS denaturation is Cys-282, Cys-145 and then Cys-253. The fourth cysteine
      residue, Cys-73, is never titrated even at high SDS/CK molar ratio. In contrast,
      the three last residues are simultaneously titrated when CK is denatured in
      guanidinium chloride. Thus, SDS-denatured CK seems to retain some residual
      organized structure. In order to confirm this hypothesis, compactness of the
      molecule was estimated by fluorescence energy transfer between CK tryptophans and
      AEDANS, an extrinsic fluorophore. The location of this fluorophore on the
      accessible thiol of Cys-282 was verified by the previous technique. The results
      of these experiments do indicate that SDS-denatured CK is more compact than CK
      completely unfolded in guanidinium chloride.

PMID- 7811688
TI  - A 1H-NMR determination of the solution structure of the A-chain of insulin:
      comparison with the crystal structure and an examination of the role of solvent.
AB  - The 1H-NMR chemical shift assignments for the oxidized A-chain of bovine insulin
      have been determined in aqueous and 30% trifluoroethanol/water solutions.
      Analysis of the observed medium-range nuclear Overhauser effects indicates that
      in aqueous solution significant populations of the peptide exist, with a 3(10)
      helical conformation over residues 12-17. This region corresponds to helix A (13
      20) in the crystal structure of the 2 Zn insulin hexamer. In 30% TFE solution,
      the NOE data are supportive of a random coil conformation throughout the peptide.

PMID- 7811689
TI  - Purification and sequencing of a family of wheat lipid transfer protein
      homologues phosphorylated by plant calcium-dependent protein kinase.
AB  - Four low molecular weight, basic proteins (WBP1A, WBP1B, WBP2 and WBP3) that are
      substrates for wheat germ Ca(2+)-dependent protein kinase (CDPK) were purified
      from wheat germ by a procedure involving batchwise cation exchange on
      carboxymethylcellulose (CM52), acid precipitation, cation exchange HPLC on an
      SP5PW column and reverse-phase HPLC on a C18 column. While WBP1A, WBP1B and WBP3
      are phosphorylated by wheat germ CDPK exclusively on Ser residues, WBP2 is
      phosphorylated on both Ser and Thr residues. CDPK-catalysed phosphorylation sites
      on WBP1A and WBP1B were determined. With all four proteins the phosphorylated
      form comigrates with non-phosphorylated protein (Mr about 9 kDa) on SDS-PAGE.
      Average molecular masses of reduced WBP1A, WBP1B, WBP2 and WBP3 measured using
      electrospray ionisation mass spectrometry (ESMS) are 9389 Da, 9274 Da, 9479 Da
      and 9467 Da, respectively. The complete amino-acid sequences of WBP1A and WBP1B
      (determined by Edman sequencing and ESMS of proteolytically derived fragments)
      and N-terminal sequences of WBP2 and WBP3 are highly homologous to each other and
      to sequences of low molecular weight, basic plant lipid transfer proteins (LTPs).

PMID- 7811690
TI  - Plasminogen activator inhibitor type-1 interacts exclusively with the proteinase
      domain of tissue plasminogen activator.
AB  - Two different techniques have been used to study the complex formation of
      recombinant human plasminogen activator inhibitor type-1, PAI-1, with either
      recombinant human two-chain tissue plasminogen activator, tc tPA (EC 3.4.21.68),
      or the tPA deletion variants tc K2P, containing the kringle 2 domain and the
      proteinase domain, and P, containing only the proteinase domain. The same value
      for Kon, 2.10(7) M-1s-1 for binding of PAI-1 was found for the three tPA forms by
      direct detection of the complex formation in real time by surface plasmon
      resonance, BIAcore, or indirectly by monitoring the time course of the inhibition
      of tPA using the chromogenic substrate N-methylsulfonyl-D-Phe-Gly-Arg-4-pNA
      acetate. Apparently, no conformational change is involved in the rate-limiting
      step, since the kon value was found to be independent of the temperature from 20
      to 35 degrees C. By the BIAcore technique, it was found that the complex between
      PAI-1 and tPA covalently coupled to the surface, was stable at 25 degrees C,
      since no dissociation was seen in buffer. However, extended treatment with 1 M
      NH4OH destroyed the complex with t 1/2 = 5 h. The same kon values and complex
      composition were found by measuring either the binding of tPA to PAI-1 captured
      on the monoclonal antibody MAI-11 or the binding of PAI-1 to tPA captured on the
      monoclonal antibody 2:2 B10. Quantification of the complex composition between
      PAI-1 captured on the monoclonal antibody MAI-11 with either tPA, K2P or P gave a
      one-to-one ratio with the fraction of active PAI-1, consistent with the results
      from SDS-PAGE and the specific activity of PAI-1. The complexes of the three tPA
      forms with PAI-1 captured on a large surface of MAI-11 dissociated more rapidly
      from MAI-11, with the same apparent koff, kdis, = 2.10(-3) s-1, compared with 0.7
      10(-3) s-1 for the dissociation of PAI-1 alone. In consistance, the Kd,
      calculated from the direct determination of the kon and koff for the association
      of different form of PAI-1 to a small surface of MAI-11, was found to be higher
      for PAI-1 in complex with tPA than for free active PAI-1. Apparently, upon
      complex formation, a change is induced in PAI-1 at the binding epitope for MAI
      11.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7811691
TI  - Effects of chloride on the kinetics and stereochemistry of chloroperoxidase
      catalyzed oxidation of sulfides.
AB  - At pH 3, chloride dramatically influenced both the Km of chloroperoxidase (CPO)
      for methyl p-tolyl sulfide, which decreased, and its activity, which increased.
      The Km value changed from 75 microM in the absence of chloride to < or = 1.2
      microM in > or = 0.9 mM chloride, and the kcat from 53 s-1 in 0 to 1750 s-1 in 50
      mM halide. The kcat/Km value at 0.9 mM chloride was 414 microM -1s-1 compared to
      0.7 microM-1s-1 in the absence of the halide. At pH 5, the activating effect was
      less pronounced. Chloride also acted as inhibitor versus hydrogen peroxide. The
      data are consistent with a reaction mechanism in which, on hand, chloride
      competes with hydrogen peroxide for the native enzyme and, on the other hand,
      activates sulfide oxidation by binding to CPO Compound I to give a CPO
      chlorinating intermediate (EOCl-). However, contrary to what happened in the
      absence of chloride, where the oxidation was enantioselective and an oxygen atom
      of H2O2 was incorporated in the sulfoxide (from experiments with 18O-labeled
      H2O2), in the presence of the halide the oxidation was not enantioselective and
      there was no incorporation of oxygen from H2O2. The data suggest that sulfide
      oxidation takes place through an enzyme-generated freely dissociable oxidized
      halogen intermediate formed by the interaction of EOCl- with Cl-.

PMID- 7811692
TI  - Thermal inactivation of shrimp deoxyribonuclease with and without sodium dodecyl
      sulfate.
AB  - Due to the differences in sample treatment, purified shrimp DNase migrates to
      different positions in sodium dodecyl sulfate (NaDod-SO4) polyacrylamide gel
      electrophoresis. DNase molecules migrating to some of these positions are
      enzymatically active as revealed by the DNase activity stain in situ. When the
      sample is not heated, DNase molecules (Form I) migrate to a position
      corresponding to an apparent Mr of 22 000 and are stain DNase-active. When the
      sample is heated with NaDod-SO4, DNase molecules (Form II) migrate to the
      apparent Mr of 39 000 position and are also DNase-active. In contrast, when the
      sample is heated without NaDod-SO4, DNase molecules (Form II') migrate to the
      same position as Form II but are DNase-inactive. When the sample is heated in the
      presence of beta-mercaptoethanol (with or without NaDod-SO4), the inactive Form
      III is generated. Form III must be the fully extended polypeptide because its
      apparent Mr is very close to the true Mr of DNase. These treated samples were
      also analyzed for DNase activity by diluting DNase-NaDod-SO4 into the DNase
      (hyperchromicity) assay solution. The results are consistent in that only Forms I
      and II are DNase-active. However, Form I differs from Form II in the time
      required for expression of DNase activity. After dilution of NaDod-SO4. Form II
      requires approx. 60 min to attain full activity while Form I is active
      immediately. Form II itself is inactive. The activity found at the Mr 39 000
      position is due to conversion of Form II to the active Form I, as revealed by two
      dimensional NaDod-SO4 gel electrophoresis. The sample heated without NaDod-SO4
      soon contains active Form II, indicating that Form II is an intermediate during
      the production of Form II'. When Form II' is heated with NaDod-SO4, it does not
      refold back to the native state through Form II, suggesting that Form II' is
      irreversibly denatured. Thus, the anomalous behaviors of shrimp DNase in NaDod
      SO4 gel electrophoresis have been utilized to study, in the presence and absence
      of NaDod-SO4, the thermal unfolding, as well as the refolding to the active
      enzyme during cooling and NaDod-SO4 removal.

PMID- 7811693
TI  - Membrane-bound high molecular mass proteinases from human erythrocytes.
AB  - Two high molecular mass proteinases, multicatalytic proteinase (MCP) and a new
      high molecular mass proteinase (HMP) with only chymotrypsin-like activity (Khan
      et al. (1994) J. Biol. Chem. 269, 10016-10021) from human erythrocyte membranes,
      have been compared. For this purpose, MCP was purified from human erythrocyte
      membranes in the active form towards synthetic peptide substrates; it also
      hydrolysed the protein substrates [14]methyl casein and [14C]oxidised insulin
      beta chain at 37 degrees C. MCP from plasma membranes exhibited hollow
      cylindrical structures also typical of cytosolic forms. Radiolabelled diisopropyl
      fluorophosphate, [3H]DFP, a serine proteinase inhibitor, labelled a band of Mr 23
      000 in membrane MCP. By contrast, no labelling was obtained with HMP.
      Chymotrypsin-like activity of HMP was also found to be insensitive to DFP. On the
      other hand, DFP inhibited chymotrypsin-like and peptidylglutamyl peptide
      hydrolysing activities of membrane MCP, with no effect on its trypsin-like
      activity. The inhibition of MCP by DFP was concentration-dependent. These studies
      showed that MCP and HMP represent two distinct kinds of proteinases with
      chymotrypsin-like activities and can be distinguished by the serine proteinase
      inhibitor DFP.

PMID- 7811694
TI  - Initial formation of a non-covalent enzyme-reagent complex during the
      inactivation of clostridial glutamate dehydrogenase by Ellman's reagent:
      determination of the enzyme's dissociation constant for the binary complex with
      NAD+ from protection studies.
AB  - The time-course of reaction between Ellman's reagent (DTNB) and clostridial
      glutamate dehydrogenase has been investigated over a wide range of reagent
      concentrations (50-5000 microM) and showed pseudo-first-order kinetics
      throughout. The reaction was followed both by monitoring loss of enzyme activity
      and by detection of released thionitrobenzoate through its absorbance at 412 nm,
      and, when both methods were used for the same DTNB concentration, the pseudo
      first-order rate constants were identical within experimental error, suggesting
      that the two methods detect the same process. The dependence of the rate
      constants on DTNB concentration clearly shows saturation, with a limiting value
      of 1.62 x 10(-3) s-1 and a dissociation constant of 1.0 mM governing the
      formation of the implied non-covalent enzyme-DTNB complex. This information has
      allowed a detailed analysis of the protection of the enzyme by NAD+, yielding a
      value of 334 microM for the dissociation constant for the enzyme-coenzyme binary
      complex. In view of the convenience of protection studies as a means of
      determining dissociation constants, this study emphasizes the importance of
      establishing whether a chemical modification reaction follows simple first-order
      kinetics with respect to the chemical reagent.

PMID- 7811695
TI  - Conformational change due to reduction of cytochrome-c oxidase in lauryl
      maltoside: picosecond time-resolved tryptophan fluorescence studies on the native
      and heat modified enzyme.
AB  - Detailed fluorescence studies on bovine heart cytochrome-c oxidase (CcO) has been
      carried out in lauryl maltoside solution. Steady-state fluorescence of the
      tryptophan residues of the enzyme showed that the fluorophores are embedded deep
      inside the hydrophobic protein cavity. Time resolved studies of tryptophan
      fluorescence of native and heat treated CcO have been carried out in both reduced
      and oxidised forms using synchronously pumped pulsed picosecond dye laser and
      single photon counting technique. Decay of the tryptophan fluorescence have been
      fitted using discrete four exponential model. Amplitude distribution of lifetimes
      also showed four distinct regions in the analysis of the decay profiles by
      maximum entropy method (MEM). The results indicate that controlled heat treatment
      of CcO affects the conformation of the enzyme near the active centers which makes
      it incapable of active proton pumping while the electron transfer property is
      still conserved. Reduction of the native CcO is associated with a large
      conformation change in lauryl maltoside near the active centers which is not
      observed in case of CcO encapsulated in vesicles. Reduction of the heat treated
      enzyme was found to have a conformation different from the reduced native CcO.

PMID- 7811696
TI  - Product inhibition of reversible enzyme-catalysed reactions.
AB  - Product inhibition studies of reversible reactions can give unusual kinetic
      patterns. A plot of rate versus substrate concentration may appear to be
      sigmoidal and the double reciprocal plot will show upward curvature. This
      apparent positive cooperativity is due to the simultaneous occurrence of both the
      forward and reverse reaction. By fitting the appropriate rate equation to the
      data it is possible to determine the maximum velocity and Michaelis constant for
      both forward and reverse reaction from experiments conducted in one direction
      only.

PMID- 7811697
TI  - Involvement of L-tryptophan aminotransferase in indole-3-acetic acid biosynthesis
      in Enterobacter cloacae.
AB  - L-Tryptophan aminotransferase (L-tryptophan:2-oxoglutarate aminotransferase; EC
      2.6.1.27) from Enterobacter cloacae was purified 62-fold and characterized to
      determine its role in indole-3-acetic acid biosynthesis. The enzyme reversibly
      catalyzed the transamination of L-tryptophan with 2-oxoglutarate as the amino
      acceptor to yield indole-3-pyruvic acid and L-glutamate, and the Km values for L
      tryptophan and indole-3-pyruvic acid were 3.3 mM and 24 microM, respectively. In
      the indole-3-acetaldehyde synthesis experiments in vitro, 94% of L-tryptophan was
      efficiently converted to indole-3-acetaldehyde by the purified L-tryptophan
      aminotransferase plus indolepyruvate decarboxylase. Furthermore, the amounts of L
      tryptophan decreased with increases in the indolepyruvate decarboxylase activity,
      while the amounts of indole-3-acetaldehyde increased with increases in this
      activity. In genetic experiments, the amounts of L-tryptophan produced by
      Enterobacter and Pseudomonas strains harboring the gene for indolepyruvate
      decarboxylase were lower than those produced by these same strains without the
      gene, while the amounts of indole-3-acetic acid produced by Enterobacter and
      Pseudomonas strains harboring the gene for indolepyruvate decarboxylase were
      higher than those produced by these same strains without the gene. These results
      clearly show that L-tryptophan aminotransferase is involved in the indole-3
      acetic acid biosynthesis and that indolepyruvate decarboxylase is the rate
      limiting step in this pathway.

PMID- 7811698
TI  - Calcyclin from mouse Ehrlich ascites tumor cells and rabbit lung form non
      covalent dimers.
AB  - Crosslinking treatments of fresh cytosol from mouse Ehrlich ascites tumor (EAT)
      cells revealed the existence of calcyclin dimers which were sensitive to SDS, but
      not to reducing agents, which suggests the existence of non-covalent dimers. In
      stored EAT cell cytosol and preparations of purified calcyclin dimers were also
      formed by S-S bridging (covalent dimers). The S-S dimers did not bind to
      organomercurial Agarose and could be separated from reduced forms of calcyclin
      that bound to the resin. Calcyclin eluted from the resin with DTT was a mixture
      of monomers and non-covalent dimers as shown by crosslinking and subsequent
      immunoblotting. Calcyclin from rabbit lung, lacking a cysteine residue, could
      also be crosslinked as a dimer. It is suggested that the ability of calcyclin to
      form non-covalent dimers is of physiological significance.

PMID- 7811699
TI  - Skeletal muscle myosin regulatory light chains conformation affects the papain
      cleavage of A1 light chains.
AB  - In the present study, the influence of magnesium-for-calcium exchange and
      phosphorylation of regulatory light chain (RLC) on accessibility of myosin and
      heavy meromyosin alkali light chains (A1) for papain digestion was investigated.
      The properties of native and papain treated myosin and heavy meromyosin were
      compared. Exchange of magnesium ions bound to RLCs for calcium ions accelerates
      the digestion of A1 in the presence of ATP in dephosphorylated myosin, heavy
      meromyosin, acto-myosin and the acto-heavy meromyosin complex. In the absence of
      ATP the exchange of magnesium ions bound to RLCs for calcium ions delays the
      digestion of A1 in the acto-myosin complex. Myosin and heavy meromyosin having
      shortened A1 by papain cleavage shows decreased K(+)-ATPase and increased actin
      binding ability in the presence and absence of ATP. The cooperation of RLC and A1
      with heavy chains in the changes of structural organization of myosin head during
      muscle contraction is discussed.

PMID- 7811700
TI  - Zinc prevents the structural and functional properties of free radical treated
      insulin.
AB  - We have previously reported that zinc deficiency could increase in vivo lipid
      peroxidation and decrease rat insulin sensitivity. In the present paper, we
      address the hypothesis of the role of zinc on insulin molecule in relation to
      free radical damage. From native recombinant human insulin, we prepared a zinc
      depleted insulin. Both preparations were subjected to controlled free radical
      attack by incubation in the presence of 2,2'-azobis(2-amidinopropane)
      hydrochloride (AAPH). To obtain minimally oxidized insulin, the oxidation process
      was monitored by measuring the intrinsic fluorescence of the insulin
      preparations. For 2.5 mM of AAPH, the autofluorescence of zinc-depleted insulin
      markedly decreased as compared to that of native insulin. These data are in favor
      of conformational changes of the insulin molecule which were further studied by
      quenching of fluorescence by means of potassium iodide. Using the euglycaemic
      hyperinsulinic glucose clamp technique in rats, the in vivo activities of the
      different insulin preparations, showed that oxidized zinc-depleted insulin had a
      marked reduced activity as compared to oxidized native insulin. From our results,
      we suggest that structural modification of the insulin molecule took place after
      zinc depletion and free radical treatment. Moreover, zinc depletion appeared to
      increase the susceptibility of insulin to free radicals.

PMID- 7811701
TI  - Residues important for folding and dimerisation of recombinant Torpedo
      californica acetylcholinesterase.
AB  - The three-dimensional crystal structure of the glycosyl phosphatidylinositol
      (GPI)-modified form of Torpedo acetylcholinesterase reveals the participation of
      Arg-44 and Glu-92 in a salt bridge and a hydrogen bond between Asp-93 and Tyr-96.
      To investigate the biological significance of these interactions, we have made
      amino acid replacements in this form of AChE: R44E, R44K, E92Q, E92L, D93N, and
      D93V. None of the introduced mutations affected the production of the
      acetylcholinesterase polypeptide significantly. However, the mutations introduced
      at position 92, as well as the D93V and R44E mutations, resulted in a total loss
      of surface located, active acetylcholinesterase. Replacement of Asp-93 with Asn
      resulted in a reduced amount of active enzyme. This mutant enzyme was
      indistinguishable from the wild-type enzyme regarding catalytic constants, but
      was more sensitive to thermal inactivation. The results show that the salt bridge
      and hydrogen bond involving residues Arg-44, Glu-92, and Asp-93 have important
      structural roles and are needed for correct folding, required for transport to
      the cell surface of TcAChE. The GPI-modified form of acetylcholinesterase is a
      disulfide bonded dimer. Cys-537 is shown to be required for the formation of the
      intersubunit disulfide bond in the dimer. Replacement with Ser resulted in the
      production of an enzyme, that migrates as a monomer upon non-reducing SDS-PAGE
      and has a lower stability compared to the dimeric wild-type enzyme.

PMID- 7811702
TI  - The alkaline phosphatase in human plexus chorioideus.
AB  - The content of alkaline phosphatase isozymes in various brain regions was
      determined by monoclonal immunocatalytic assays. The levels of the isozymes in
      human brain tissues were low compared with those in other human tissues, liver,
      kidney, bone, intestine and placenta. Plexus chorioideus in the brain, however,
      was found to express significant amounts of alkaline phosphatase activity. The
      purified isozyme from human plexus chorioideus demonstrated a single 70 kDa
      protein band on SDS-polyacrylamide gel which coincides with that of tissue
      unspecific alkaline phosphatase from human liver. The isozyme expressed in the
      plexus was confirmed to be the tissue-unspecific alkaline phosphatase isozyme
      with regard to its reactivity with monoclonal antibodies specific for liver
      alkaline phosphatase, heat stability, and the inhibition by amino acids. This
      finding adds new dimensions to the functional role this isozyme may play.

PMID- 7811703
TI  - Divalent metal ions induce conformational change in pure, human wild-type p53
      tumor suppressor protein.
AB  - The ability of wild-type and not mutant p53 to exert antiproliferative effects on
      normal cells may be related to a difference in the conformational state of the
      protein. We have used pure, human wild-type p53 and a panel of monoclonal
      antibodies whose epitopes map throughout the protein to assess whether divalent
      metal ions affect the conformation of p53. Our results show that the presence of
      Zn2+ ions at physiological concentrations, directly reduced or blocked
      accessibility of epitopes on pure wild-type p53, an effect which was reversed by
      chelating agents. Loss of epitope reactivity was maximal between the protein mid
      region and C-terminus. Analytical sucrose density gradient ultracentrifugation
      studies also confirmed that Zn(2+)-induced conformational changes partially
      affected the pattern of p53 oligomerisation. The observed binding of pure p53 to
      a sequence-specific DNA motif was unaffected by the presence of added Zn2+ ions
      or metal chelating agents.

PMID- 7811704
TI  - Molecular cloning and sequencing of a human cDNA encoding ornithine decarboxylase
      antizyme.
AB  - We report the cloning of a cDNA encoding the human homolog of ornithine
      decarboxylase antizyme from a human gingival fibroblast cDNA library. The human
      antizyme is 84% identical to the rat sequence and shows almost no homology to the
      E. coli antizyme. Northern analysis studies show that this gene is expressed in
      both human gingival and synovial fibroblasts.

PMID- 7811705
TI  - Regulation of cholesteryl ester transfer protein (CETP) activity: review of in
      vitro and in vivo studies.

PMID- 7811706
TI  - Structure of polymerizable lipid bilayers VII: lateral organization of
      diacetylenic phosphatidylcholines with short proximal acyl chains.
AB  - As an extension of recent results (Rhodes, Xu and Bittman (1992) Biochim.
      Biophys. Acta 1128, 93; Hui, Xu and Bittman (1992) Langmuir 8, 2724) with a C18
      diacetylenic phosphatidylcholine, bilayers of 1,2-bis(pentacosa-4,6-diynoyl)-sn
      glycero-3-phosphocholine (C25) were investigated using X-ray diffraction on
      multibilayers and electron diffraction on Langmuir-Blodgett deposited bilayers.
      Monolayers of this lipid form solid (gel phase) domains at pi > 14 mN/m. Electron
      diffraction data indicated that the chain spacing in these domains is 4.25 A and
      that the chains are tilted at angle of approximately 35 degrees relative to the
      bilayer plane. Wide angle data from X-ray diffraction experiments indicated a
      similar spacing and chain tilt. Small angle data showed that the lamellar repeat
      was 70 A at high humidity and < or = 60 A at low humidity. The bilayer electron
      density profiles indicated a bilayer structure with no interdigitation. High
      angle reflections indicate that the principal acyl chain repeat is preserved as a
      function of hydration but some rearrangement occurs for other reflections. The
      approximately 10 A reflection corresponding to the headgroup spacing previously
      observed with C18-diacetylenic phosphatidylcholine bilayers was not observed. The
      results are interpreted in terms of a packing model and possible limitations or
      constraints to the polymerization process.

PMID- 7811707
TI  - Effect of squalestatin 1 on the biosynthesis of the mevalonate pathway lipids.
AB  - The effects of squalestatin 1 on rat brain and liver homogenates and on Chinese
      hamster ovary tissue culture cells have been investigated. This compound
      effectively inhibits squalene biosynthesis in a highly selective manner.
      Cytoplasmic farnesyl pyrophosphate and geranylgeranyl pyrophosphate synthases are
      not affected, which is also the case for microsomal cis-prenyltransferase. In
      tissue culture cells, squalestatin 1 inhibits cholesterol biosynthesis
      completely, but does not alter dolichol synthesis or protein isoprenylation to a
      great extent. Incorporation of [3H]mevalonate into ubiquinone-9 and -10 increases
      3-4-fold, probably as a result of increased synthesis of this lipid. Squalestatin
      1 appears not only to be an effective inhibitor of cholesterol biosynthesis, but
      also to be more specific than other inhibitors used earlier in various in vitro
      and in vivo systems.

PMID- 7811708
TI  - The effects of free radical scavengers on the oxidation of low-density
      lipoproteins by macrophages.
AB  - Oxidised LDL has been implicated in the pathogenesis of atherosclerosis.
      Macrophages can oxidatively modify low-density lipoprotein (LDL) in vitro. The
      mechanisms of this oxidation process are presently unclear. In this study, we
      have investigated the effects of compounds and enzymes widely used to quench or
      scavenge active oxygen species to try to identify the oxidative species involved
      in this process. The data obtained suggest that hydrogen peroxide may possibly
      play a role in LDL oxidation by macrophages, whereas singlet oxygen and hydroxyl
      radicals may not. The role of superoxide anions was uncertain because copper-zinc
      superoxide dismutase (Cu/Zn-SOD) and manganese SOD (Mn-SOD), widely used to
      determine superoxide-dependency in other systems may be unsuitable in this
      particular system. Cu/Zn-SOD at high concentrations displayed a variability in
      its effects, sometimes augmenting LDL oxidation and sometimes inhibiting it. In
      the experiments in which Cu/Zn-SOD augmented LDL oxidation, heat inactivation of
      the enzyme decreased the augmentation; in the experiments in which Cu/Zn-SOD
      inhibited LDL oxidation, it retained its inhibitory effect after heat
      inactivation. Mn-SOD always inhibited modification even after heat inactivation.
      We have therefore concluded that superoxide involvement in LDL oxidation by
      macrophages is still uncertain and the uncertainty will remain until a suitable
      probe is found.

PMID- 7811709
TI  - Peroxidation of egg yolk phosphatidylcholine liposomes by hypochlorous acid.
AB  - The powerful neutrophil-derived oxidant hypochlorous acid HOCl/OCl- is assumed to
      contribute to tissue injury in a number of pathological states accompanied by
      massive accumulation of neutrophils. The production of malondialdehyde to
      indicate lipid peroxidation was studied in egg yolk phosphatidylcholine liposomes
      upon treatment with NaOCl as a source for hypochlorous acid. Its accumulation was
      inhibited by alpha-tocopherol and butylated hydroxytoluene. Singlet oxygen,
      hydroxyl radicals or superoxide anion radicals derived from direct reactions of
      hypochlorous acid seem not to be involved in initiation of lipid peroxidation
      because the malondialdehyde accumulation was unaffected by hydrogen peroxide,
      catalase, superoxide dismutase, ferrous sulphate or ferric chloride. Double bonds
      of fatty acid residues seem to be the primary target for NaOCl. Their number is
      continuously diminished in liposomes (2 mg lipids/ml) after incubation with
      increasing amounts of NaOCl at 37 degrees C for 40 min as detected by two
      independent methods (iodine bromide reduction and 1H-NMR spectroscopy). A 1:1
      molar ratio between the loss of double bonds and NaOCl added was found only at
      low NaOCl concentrations. Then double bonds are decreased with a lower
      efficiency. A continuous increase of lipid peroxidation products was only
      observed up to 0.5-0.7 mmol/l NaOCl. The yield of lipid hydroperoxides kept
      constant at higher NaOCl concentrations. However, diene conjugates and
      malondialdehyde exhibit a maximum at 0.7-1 mmol/l or 0.5 mmol/l NaOCl,
      respectively, while the concentration of these products decreases at higher doses
      of NaOCl. The decrease of malondialdehyde was more pronounced than for diene
      conjugates. These results were discussed from the background that at minimum two
      (diene conjugates) or three (malondialdehyde) double bonds in a fatty acid
      residue are necessary for formation of lipid peroxidation products.

PMID- 7811710
TI  - Lipid oxidation, lipoprotein cell-association and ceroid accumulation in P388D1
      macrophage-like cells.
AB  - Flow cytometry can be used to quantify the accumulation of ceroid in macrophages,
      the result of cellular handling of certain lipoproteins. Using P388D1 cells, a
      murine-derived macrophage-like cell line, the effect of the lipophilic
      antioxidant, DL-alpha-tocopherol, upon the uptake and accumulation of ceroid by
      the cells was monitored on culture with artificial lipoproteins containing a
      single lipid species. Ceroid accumulation was greater for artificial lipoprotein
      composed of BSA complexed with cholesteryl arachidonate, than with cholesteryl
      linoleate. alpha-Tocopherol inhibited the ceroid accumulation, which was also
      dependent upon cell density. Thus, since these findings are similar to recent
      observations in primary cultures of murine peritoneal macrophages, it would
      appear that macrophage-like cell lines such as P388D1 cells are appropriate for
      the study of potential agonists and antagonists of lipid oxidation. Culture of
      P388D1 cells with oxidised human low-density lipoprotein (LDL) also resulted in
      ceroid formation, shown to be dependent upon the level of LDL oxidation as
      assessed by thiobarbituric acid-reactivity, the xylenol orange assay of peroxides
      and gas chromatographic analysis of cholesterol and fatty acid content. Ceroid
      accumulation reflected changes in the level of LDL oxidation better than did the
      cell association of oxidised radiolabelled LDL, monitored as that bound and
      retained by the cell.

PMID- 7811711
TI  - Effect of starvation on lipoprotein lipase activity in different tissues during
      gestation in the rat.
AB  - This study was addressed to determine whether the tissue-specific LPL activity
      response to fasting differs between nonpregnant and pregnant rats over the course
      of pregnancy. Fed and 24-h fasted rats were studied at days 12, 15 or 20 of
      gestation and were compared to virgin controls. In fed rats at days 15 and 20 of
      gestation LPL activity decreased in lumbar adipose tissue and the heart and
      liver, and increased in mammary gland tissue. Fasting decreased LPL activity in
      lumbar adipose tissue in 12 day pregnant and virgin rats and in mammary gland
      tissue in pregnant rats at 15 and 20 days of gestation and in virgin rats,
      whereas it increased LPL activity in heart tissue in rats at day 15 and 20 and in
      liver at day 20 of gestation. Plasma triacylglycerols were higher in 20 day
      pregnant rats than in the other groups when fed and this difference was even more
      noticeable in the fasting condition where the plasma beta-hydroxybutyrate level
      also reached the highest value in the 20 day pregnant rats. Since tissue LPL
      activity controls the hydrolysis and uptake of circulating triacylgylcerols, the
      present results indicate that in fed rats after the 15th day of gestation
      circulating triacylglycerols are preferentially taken up by the mammary gland
      instead of being taken up by adipose tissue and heart. However, after fasting,
      circulating triacylglycerols are driven to the heart and liver in the late
      pregnant rat, and become a major source for fatty acid oxidation, an effect that
      seems to be specially evident in the liver of the 20 day pregnant rat where there
      is an intense increase in LPL activity and the triacylglycerols become
      preferential substrates for ketone body production.

PMID- 7811713
TI  - Thromboxane A2 synthase activity in platelet free human monocytes.
AB  - Soon after platelets, the highest amounts of thromboxane A2 (TXA2) can be
      detected in human monocytes activated by serum. Using platelet-free human
      monocytes, we have shown that foetal calf serum (FCS) induces prostaglandin H
      synthase (PGH synthase) after 16 h of incubation, as shown by the use of
      transcriptional inhibitors and Western blotting. The effect of serum can be in
      part mimicked by recombinant colony stimulating factor-1 (hr CSF-1). It is not
      known whether the limiting step leading from arachidonate to TXA2 is represented
      solely by the level of PGH synthase or also by the level of TXA2 synthase. We
      approached this problem by using a Western blot specific for the enzyme, as well
      as by using PGH2 as substrate. The results show that TXA2 synthase is
      constitutively expressed in monocytes, i.e., its levels were high soon after
      their isolation, and similar to those observed after 24 h of incubation with
      serum. However TXA2 failed to be synthesized until at least 3 h of incubation,
      and the pattern of synthesis was dependent on the kinetics of PGH synthase
      induction. In any condition in which TXA2 synthase was immunodetectable, using
      PGH2 as substrate a high rate of conversion to TXB2 could be detected.
      Experiments with actinomycin D and cycloheximide indicate that the half-life of
      TXA2 synthase was longer than 16 h, therefore much longer than that of PGH
      synthase, that the gene coding for it is fully active in resting monocytes, and
      that the conversion of arachidonate to TXA2 induced by serum or CSF-1 is
      dependent solely on the de novo synthesis of PGH synthase.

PMID- 7811712
TI  - Important contribution of the methylene part of LTB4 toward binding affinity to
      the LTB4 receptors and rise in intracellular-free calcium concentration.
AB  - In order to examine a role of the C(16)-C(20) methylene part of leukotriene B4
      (LTB4) toward the activation of leukocytes, we synthesized the LTB4-analogues in
      which the length of the C(16)-C(20) part of LTB4 is varied systematically while
      the two hydroxyl groups at C(5) and C(12) positions and the 6(Z), 8(E), 10(E)
      conjugated triene unit remained untouched. We examined their binding affinity to
      the LTB4 receptors present in the rat polymorphonuclear leukocytes (PMNLs) and
      their ability to raise intracellular-free calcium concentration ([Ca2+]i) in the
      rat PMNLs loaded with fura-2. As the length of the chain of LTB4 was increased or
      decreased one by one, the binding affinity to the LTB4 receptors diminished, and
      the analogues of more than three carbon atoms shorter chain were of about three
      log order less activity than LTB4. The biological potency as assessed in [Ca2+]i
      rises pararelled that of the binding affinity to the PMNL membrane. These results
      indicate that the C(16)-C(20) part of LTB4 plays important role for the activity.
      In a similar way we prepared the LTB4-analogues of a different chain length
      between C(2)-C(4) of LTB4 and tested their biological activity. We found that the
      C(2)-C(4) part of LTB4 also affects the activity.

PMID- 7811714
TI  - Eicosanoid generation and effects on the aggregation of thrombocytes from the
      rainbow trout, Oncorhynchus mykiss.
AB  - Fish blood lacks anucleate platelets but contains a nucleated cell type termed
      the thrombocyte that is thought to be functionally analogous. Thrombocytes were
      purified from the peripheral blood of the rainbow trout, Oncorhynchus mykiss, by
      a two step gradient centrifugation method. Following this procedure, the
      recovered thrombocytes were 78-86% pure as defined by immunoreactivity to a panel
      of monoclonal antibodies and were of variable morphology from round to spindle
      shaped. Incubation of thrombocyte suspensions with either calcium ionophore,
      A23187, platelet-activating factor or a thromboxane (TX) mimetic, U-46619,
      generated a range of eicosanoids derived from arachidonic acid including 12
      hydroxyeicosatetraenoic acid (12-HETE), TXB2, prostaglandin (PG) E2, leukotriene
      (LT) B4 and lipoxin (LX) A4. The equivalent products derived from
      eicosapentaenoic acid were also formed. Co-incubation of thrombocytes with either
      erythrocytes or granulocytes/monocytes in the presence of calcium ionophore did
      not result in the formation of any further new lipoxygenase products. Incubation
      of isolated thrombocytes in plasma-free conditions with U-46619 (0.03-10 microM)
      resulted in a rapid, dose-dependent aggregatory response. This effect was
      markedly augmented in the presence of mammalian fibrinogen (400 micrograms ml-1).
      Thrombin (0.1-1.3 units ml-1), like U-46619, was also a potent proaggregatory
      compound for trout thrombocytes. LXA4 and LTB4 had limited aggregatory potential
      and then only at high concentrations (10 microM), while 12-HETE and PAD had no
      significant effect at all concentrations tested. These results demonstrate that
      some of the eicosanoids released during the activation of trout thrombocytes are
      involved in the aggregatory behaviour of this cell type.

PMID- 7811715
TI  - Human 5-lipoxygenase associates with phosphatidylcholine liposomes and modulates
      LTA4 synthetase activity.
AB  - A Ca2+ and a phosphatidylcholine (PC) as stimulatory factors to human 5
      lipoxygenase (5-LO) were assessed to examine aspects of the regulatory mechanism
      of 5-LO. In the presence of Ca2+ (1 microM or less), PC liposomes distinctly
      stimulated the dual activities of 5-LO for the production of 5-HPETE from
      arachidonate and for its subsequent conversion to LTA4. At the same concentration
      of Ca2+, 5-LO was found to bind to PC liposomes. As with 5-LO activities, the
      binding was dependent on the range of Ca2+ concentration. The conversion ratios
      of 5-HPETE to LTA4 were dependent on PC liposome concentration and reached a
      maximum of 50% conversion. Among the four cell membrane lipids examined, PC
      liposomes demonstrated the highest conversion ratio of 5-HPETE to LTA4 by 5-LO.
      Most of the arachidonate added to the reaction mixture localized in PC liposomes.
      These results confirm that the intracellular increase of Ca2+ concentration
      causes 5-LO to associate with the cell membrane and perform an interfacial
      reaction. They also suggest that this binding of 5-LO to the cell membrane
      enhances the subsequent conversion from 5-HPETE to LTA4.

PMID- 7811716
TI  - Interaction between apo A-I-containing lipoproteins and lecithin:cholesterol
      acyltransferase.
AB  - HDL2 and HDL3 subfractions of two species of apo A-I-containing lipoprotein, one
      containing only apo A-I (LpA-I) and the other containing both apo A-I and apo A
      II (LpA-I/A-II), were tested for reactivity to lecithin:cholesterol
      acyltransferase (LCAT). These subfractions and their mixtures were incubated with
      lipoprotein-deficient plasma (LCAT source), and the rate of cholesterol
      esterification and kinetic parameters were determined. Apparent Vmax (appVmax)
      and apparent Km (appKm) for HDL2 subfractions of LpA-I and LpA-I/A-II were
      significantly lower than those of their HDL3 counterparts. Differences between
      subfractions were much more prominent in LpA-I than in LpA-I/A-II. appVmax of the
      HDL2 subfraction of LpA-I (LpA-IHDL2) was one-fifth, and appKm was one-third of
      those for the HDL3 subfraction (LpA-IHDL3). appVmax and appKm of LpA-IHDL2 were
      both lowest among the apo A-I-containing lipoprotein subfractions. When LpA-IHDL2
      was added to other subfractions, the molar rate of cholesterol esterification was
      suppressed. Since LpA-IHDL2 consists of a particle 11.1 nm in diameter, our
      observations suggest that LpA-IHDL2 suppresses cholesterol esterification in apo
      A-I-containing lipoprotein, possibly by displacing LCAT from other subfractions
      with higher appKm and higher appVmax to 11.1 nm LpA-I particles with lower appKm
      and lower appVmax. All of these data suggest that the relative amount of 11.1 nm
      LpA-I particles in plasma regulates the reactivity of apo A-I-containing
      lipoprotein to LCAT and may play a key role on the production of cholesteryl
      esters in plasma.

PMID- 7811717
TI  - In vivo turnover of phospholipids in rabbit erythrocytes.
AB  - The rate of phospholipid turnover in erythrocyte membranes in vivo has been
      studied using a recently developed procedure (Kuypers, F.A., Easton, E.W., van
      den Hoven, R., Wensing, T., Roelofsen, B., Op den Kamp, J.A.F. and van Deenen,
      L.L.M. (1985) Biochim. Biophys. Acta 819, 170-178). The technique is based on the
      application of phospholipid transfer proteins in order to introduce trace amounts
      of radiolabelled phospholipids in the membrane of isolated erythrocytes, followed
      by re-injection of the erythrocytes into the bloodstream of the animal. The most
      abundant species of the phosphatidylcholine (PC) class, 1-palmitoyl,2-linoleoyl
      PC, has, on the basis of loss of the radioactivity in its fatty acyl part, a
      relatively high turnover with a half-time value of 1.5 days. Other PC species
      studied exhibit more moderate turnover rates of about 5 days for 1-palmitoyl,2
      oleoyl PC and 1-stearoyl,2-arachidonoyl PC. Dipalmitoyl PC, labelled in the polar
      headgroup, turns over at a slow rate with a half-time value of 9 days. From these
      data and the relative abundance of the various species, it can be calculated
      that, on a daily basis in vivo, about one third of the total PC pool in rabbit
      erythrocyte membranes is replaced and/or modified by de-/reacylation. The only
      phosphatidylethanolamine (PE) species studied so far, 1-palmitoyl,2-arachidonoyl
      PE, appeared to be renewed at a relatively low rate with a half-time value of 12
      days. The data demonstrate that the in vivo turnover values of phospholipids in
      the erythrocyte membrane may depend on their polar head group structure, their
      localization in the membrane and, to a large extent, on their fatty acid
      composition.

PMID- 7811718
TI  - Long-chain fatty acid-binding to albumin: re-evaluation with directly measured
      concentrations.
AB  - In studies on uptake of fatty acids (FA) into organs, the unbound (or free) fatty
      acid fraction is commonly calculated from the concentration bound to albumin and
      from published binding constants. However, there is some dispute on the methods
      used for determining those binding constants. We developed a method allowing
      direct measurement of unbound FA by extending the previous studies of Svenson et
      al. [1] and Reed et al. [2]. Albumin was coupled to a solid phase (Sepharose 4B),
      loaded with FA and equilibrated with an aqueous solution. Laurate, palmitate and
      oleate concentrations in the aqueous phase were determined at different molar
      ratios of FA to albumin (r) and at different temperatures. FA albumin-binding
      constants (Ki) increase with chain length and decrease with temperature, in
      accordance with data obtained by others. However, the unbound concentrations
      measured are markedly lower than those obtained from binding constants, and the
      resulting Ki values markedly higher. This difference is presumed to result from
      (1) our direct measurement of unbound FA and (2) utilizing different more
      physiological conditions. Recalculating kinetic parameters from published FA
      uptake data, we found considerably different Km and Vmax values compared to the
      original data. Thus, the FA-binding characteristics measured in this study may
      influence the interpretation of FA uptake substantially.

PMID- 7811719
TI  - Cytosolic lipoprotein particles from milk-secreting cells contain fatty acid
      synthase and interact with endoplasmic reticulum.
AB  - Part of the fatty acid synthase in cytosol from mammary glands of lactating rats
      was in a complex with other proteins and with lipids. This complex eluted in the
      void volume from a gel filtration column with an exclusion limit of 5,000,000,
      and remained in a 3% polyacrylamide stacking gel during electrophoresis under
      nondenaturing conditions. Fatty acid synthase-containing lipoprotein particles
      ranged in density from 1.07 to 1.16 g/ml, and varied in protein to lipid ratios.
      Similar fatty acid synthase particles were present also in cytosol from cow
      mammary gland. Butyrophilin, xanthine oxidase, and a group of small GTP-binding
      proteins that included ADP-ribosylation factor, were identified as constituents
      of the lipoprotein complex. This complex interacted with endoplasmic reticulum
      and with lipid droplets in cell-free incubation mixtures. In ultrastructure fatty
      acid synthase-containing lipoprotein particles were homogeneous in appearance,
      but were heterogeneous in size, with apparent diameters of 40 to 170 nm.
      Immunocytochemically, antigen recognized by antibodies to fatty acid synthase
      were found to be present in these particles and on endoplasmic reticulum.
      Lipoprotein complexes bound to specific polypeptides of endoplasmic reticulum.

PMID- 7811720
TI  - Possible role of calcium in phospholipid synthesis of Microsporum gypseum.
AB  - The effect of calcium on lipid synthesis in Microsporum gypseum was examined by
      growing these cells in calcium supplemented (1 mM to 10 mM) medium. Maximum
      incorporation of [14C]acetate into total lipids and phospholipids was observed in
      cells grown with 6 mM calcium. This was probably due to a 3-fold increase in
      total calcium levels as incorporation of label was inhibited in total lipids
      (33%) and phospholipids (20.5%) in calcium-grown cells which were preincubated
      with the calcium specific chelator ethylene glycolbis (beta-aminoethyl ester)
      N,N,N',N',-tetracetate (EGTA). Increased incorporation of [14C]acetate into
      phospholipids was further supported by increase in the activity of key
      phospholipid biosynthetic enzymes (glycerolkinase and glycerol-3-phosphate
      acyltransferase) as well as the increase in phospholipid content in calcium-grown
      cells, which suggests a correlation between increased calcium levels and
      phospholipid biosynthesis in M. gypseum.

PMID- 7811721
TI  - Structures of glucolipids from the membrane of Acholeplasma laidlawii strain A
      EF22. II. Monoacylmonoglucosyldiacylglycerol.
AB  - The structure of one glucolipid from the membrane of Acholeplasma laidlawii,
      strain A-EF22, was determined. This glucolipid is synthesized only when a large
      fraction of saturated, straight-chain fatty acids are incorporated into the
      membrane lipids of strain A-EF22. The lipid was studied by 1H- and 13C-NMR
      spectroscopy. The structure of the lipid is 1,2-diacyl-3-O-[6-O-acyl-(alpha-D
      glucopyranosyl)]-sn-glycerol. The result for this lipid shows that a previously
      published structure, based on incomplete chemical analyses, was incorrect. The
      phase equilibria for 1,2-diacyl-3-O-[6-O-acyl-(alpha-D-glucopyranosyl)]- sn
      glycerol and the two dominating lipids in A. laidlawii,
      monoglucosyldiacylglycerol and diglucosyldiacylglycerol, are discussed and
      related to the chemical structure of the lipids.

PMID- 7811722
TI  - Molecular basis of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency:
      identification of the major disease-causing mutation in the alpha-subunit of the
      mitochondrial trifunctional protein.
AB  - Mitochondrial trifunctional protein is a newly identified enzyme involved in
      mitochondrial fatty acid beta-oxidation harbouring long-chain enoyl-CoA
      hydratase, long-chain 3-hydroxyacyl-CoA dehydrogenase and long-chain 3
      ketothiolase activity. Over the last few years, we identified more than 26
      patients with a deficiency in long-chain 3-hydroxyacyl-CoA dehydrogenase. In
      order to identify the molecular basis for the deficiency found in these patients,
      we sequenced the cDNAs encoding the alpha- and beta-subunits which revealed one G
      ->C mutation at nucleotide position 1528 in the 3-hydroxyacyl-CoA dehydrogenase
      encoding region of the alpha-subunit. The single base change results in the
      substitution of a glutamate for a glutamine at amino acid position 510. The base
      substitution creates a PstI restriction site. Using RFLP, we found that in 24 out
      of 26 unrelated patients only the C1528 was expressed. The other two patients
      were heterozygous for this mutation. This mutation was not found in 55 different
      control subjects. This indicates a high frequency for this mutation in long-chain
      3-hydroxyacyl-CoA dehydrogenase deficient patients.

PMID- 7811723
TI  - Structural requirements for dimerization, glycosylation, secretion, and
      biological function of VPF/VEGF.
AB  - Vascular permeability factor (VPF) also known as vascular endothelial growth
      factor (VEGF), is a dimeric protein that affects endothelial cell (EC) and
      vascular functions including enhancement of microvascular permeability and
      stimulation of EC growth. To investigate the structural features of VPF/VEGF
      necessary for efficient dimerization, secretion, and biological activities, we
      employed site-directed mutagenesis with a Cos-1 cell expression system. Several
      cysteine residues essential for VPF dimerization were identified by mutation
      analysis of the Cys-25, Cys-56, and Cys-67 residues. Mutant VPF isoforms lacking
      either of these cysteines were secreted as monomers and were completely inactive
      in both vascular permeability and endothelial cell mitotic assays. VPF Cys-145
      mutant protein was efficiently secreted as a glycosylated, dimeric polypeptide,
      but had a reduction in biological activities. The site of N-linked glycosylation
      was directly identified as Asn-74, which, when mutated produced an inefficiently
      secreted dimeric protein without post-translational glycosylation, yet maintained
      full vascular permeability activity. Finally, we found that one VPF mutant
      isoform Cys-101 was not secreted and this mutant functioned as a dominant
      negative suppressor of wild-type VPF secretion as demonstrated by co-expression
      assays in Cos-1 cells.

PMID- 7811724
TI  - Heat denaturation of human orosomucoid in water/methanol mixtures.
AB  - Heat denaturation of orosomucoid in solutions of methanol concentrations ranging
      from 0 to 70% (v/v) has been studied by using circular dichroism, intrinsic
      protein fluorescence and thermal difference absorption spectroscopy. Regardless
      of its high saccharide content (40%), the highly cooperative denaturation
      transition of orosomucoid is fully reversible in neutral water solution. A two
      state model has been successfully applied; the numerical analysis results in
      thermodynamical parameter values that are in close agreement with previously
      reported experimental data from calorimetric measurements. However, in solutions
      containing even minute concentrations of methanol (5%) the heat denaturation is
      irreversible. After cooling of the denatured protein the refolded molecules
      exhibit a higher alpha-helical content than the native one. Possibilities of
      methanol interaction with native and denatured protein molecule are discussed.

PMID- 7811725
TI  - Characterization of the interactions of NADH with the dimeric and tetrameric
      states of methaemoglobin.
AB  - The binding of NADH to the dimeric (alpha beta) and tetrameric (alpha 2 beta 2)
      states of human aquomethaemoglobin has been characterized by sedimentation
      equilibrium studies of the effect of the concentration of free ligand on the
      macromolecular state of the haemoprotein. Both macromolecular states of
      aquomethaemoglobin exhibit a single binding site for NADH, which interacts
      approximately tenfold more strongly (6000 cf. 700 M-1) with the tetramer under
      the conditions studied (pH 6.0, I 0.10). Because the structure of
      aquomethaemoglobin resembles that of the deoxy state of haemoglobin, there is a
      high probability that organic phosphates also bind to dimeric deoxyhaemoglobin, a
      phenomenon which is not considered in thermodynamic treatments of the interplay
      between oxygen binding and its allosteric inhibition by 2,3-bisphosphoglycerate.
      Fortunately, the equilibrium constant for deoxyhaemoglobin self-association is so
      large that neglect of the interaction between allosteric inhibitor and dimeric
      haemoglobin is an oversight that should have no deleterious implications in the
      resultant thermodynamic analysis of the interplay between the preferential
      interactions of oxygen and organic phosphate with the various macromolecular
      states of deoxyhaemoglobin.

PMID- 7811726
TI  - Carbon-13 NMR studies of the influence of axial ligand orientation on haem
      electronic structure.
AB  - Three-quarters of the carbon-13 resonances of nuclei attached to the four haems
      of Desulfovibrio vulgaris ferricytochrome c3 are assigned. Preliminary analysis
      of their Fermi contact interactions shows that the shifts are directly related to
      the orientation of both of the axial histidine ligands in each case and the
      approach can therefore be used to obtain structural information in other
      cytochromes with bis-histidinyl coordination. The implications for the control of
      redox potential in cytochromes are discussed.

PMID- 7811727
TI  - Reactive site mutants of recombinant protein C inhibitor.
AB  - Protein C inhibitor (PCI) is a heparin-binding serine proteinase inhibitor
      (serpin) which is thought to be a physiological regulator of activated protein C
      (APC). The residues F353-R354-S355 (P2-P1-P1') constitute part of the reactive
      site loop of PCI with the R-S peptide bond being cleaved by the proteinase.
      Changing the reactive site P1 and P2 residues to those of either proteinase nexin
      1, alpha 1-proteinase inhibitor or heparin cofactor II resulted in a decrease in
      inhibitory activity towards thrombin and APC. Changing the P2 residue F353-->P
      generated a rPCI which was a better thrombin inhibitor, but was 10-fold less
      active with APC. While these results support the concept that the P1 and P2
      residues are important in the specificity of PCI, they suggest that the reactive
      site residues are not the only determinant of serpin specificity. Kinetic
      analysis of the rPCI variants was consistent with PCI operating by a mechanism
      similar to that proposed for other serpins. In this model an intermediary complex
      forms between inhibitor and proteinase that can proceed to either cleavage of the
      inhibitor as substrate or formation of an inactive complex.

PMID- 7811728
TI  - Hemoglobin Roanne [alpha 94(G1) Asp-->Glu]: a variant of the alpha 1 beta 2
      interface with an unexpected high oxygen affinity.
AB  - In hemoglobin (Hb) Roanne, the aspartate residue alpha 94(G1) is replaced by a
      glutamic acid. This residue plays a key role in the structural changes affecting
      the alpha 1 beta 2 contact area during the deoxy- to oxy-state transition in the
      hemoglobin molecule. Aspartate alpha 94(G1) is involved in several contacts both
      in the deoxy- and oxy-structures. The most important of those is a hydrogen bond
      with asparagine beta 102 (G4), stabilizing the oxygenated structure. Alteration
      of this contact usually leads to a decrease in oxygen affinity. Hb Roanne is the
      first example in which an increased oxygen affinity was found as a result of a
      structural modification at this position. Functional data suggested that the
      mechanisms responsible for this altered property are a destabilisation of the T
      structure and a modification of the allosteric equilibrium.

PMID- 7811729
TI  - Structural and functional characterization of bovine adrenodoxin reductase by
      limited proteolysis.
AB  - Previously, we have proposed that bovine adrenocortical mitochondrial adrenodoxin
      reductase may possess a domain structure, based upon the generation of two major
      peptide fragments from limited tryptic proteolysis. In the present study, kinetic
      characterization of the NADPH-dependent ferricyanide reductase activity of the
      partially proteolyzed enzyme demonstrates that Km(NADPH) increases (from 1.2
      microM to 2.7 microM), whereas Vmax remains unaltered at 2100 min-1. The two
      proteolytic fragments have been purified to homogeneity by reverse-phase HPLC,
      and amino-acid sequence analysis unambiguously demonstrates that the 30.6 kDa
      fragment corresponds to the amino terminal portion of the intact protein, whereas
      the 22.8 kDa fragment is derived from the carboxyl terminus of the reductase.
      Trypsin cleavage occurs at either Arg-264 or Arg-265. Covalent crosslinking
      experiments using a water-soluble carbodiimide show that adrenodoxin crosslinks
      exclusively to the 30.6 kDa fragment, thus implicating the N-terminal region of
      adrenodoxin reductase in binding to the iron-sulfur protein. Our inability to
      detect covalent carbohydrate on either intact or proteolyzed adrenodoxin
      reductase prompted a re-examination of the previously reported requirement of an
      oligosaccharide moiety for efficient electron transfer from the reductase to
      adrenodoxin. Treatment of adrenodoxin reductase with a highly purified
      preparation of neuraminidase demonstrates that neither the adrenodoxin
      independent ferricyanide reductase activity nor the adrenodoxin-dependent
      cytochrome c reductase activity of the enzyme is affected by neuraminidase
      treatment.

PMID- 7811730
TI  - Substrate specificity of tissue kallikreins: importance of an extended
      interaction site.
AB  - The contribution of an extended interaction site in tissue kallikreins to their
      substrate specificity was investigated using peptides of increasing length and
      with different amino acids in positions P5 and P6. These substrates were
      constructed from a consensus dodecapeptide sequence (VASPFRSYDLDA) deduced from
      the hydrolysis of short synthetic peptide substrates, and from the identification
      of the cleavage sites in reduced-pyridylethylated lysozyme by 6 rat tissue
      kallikreins. Though the specificity constant kcat/Km generally increases with
      increasing the peptide substrate length on its N-terminal end, individual
      residues at P4-P6 may specifically alter this value for specific kallikreins. A
      seryl residue at P4 induces a 20-fold decrease in the specificity constant with
      rK2 and rK9, but it slightly improves this value for rK1 and rK10. A tryptophan
      in P6 is unfavourable for both rK1 and rK2 but not for rK9 and rK10, whereas a
      negatively charged residue has a negative effect for all four kallikreins. This
      demonstrates the importance of an extended interaction site in kallikreins, and
      suggests that the differing specificities of individual kallikreins are partly
      due to the presence of proteinase subsites which accommodate residues remote from
      the scissile bond in the substrate. These sites could be located in variable
      loops that surround the kallikrein active sites, and correspond to regions of
      lower structural similarity. Molecular modeling studies indicate that loop 4 may
      contribute to the P4-P7 specificity of kallikreins.

PMID- 7811731
TI  - Purification and immunochemical characteristics of NADPH-cytochrome P-450
      oxidoreductase from tobacco cultured cells.
AB  - NADPH-cytochrome P-450 oxidoreductase (EC 1.6.2.4) was purified from the
      microsomal fraction of tobacco (Nicotiana tabacum) BY2 cells by chromatography on
      two anion-exchange columns and 2',5' ADP-Sepharose 4B column. The purified enzyme
      showed a single protein band with a molecular weight of 79 kDa on SDS-PAGE and
      exhibited a typical flavoprotein redox spectrum, indicating the presence of an
      equimolar quantity of FAD and FMN. This enzyme followed Michaelis-Menten Kinetics
      with Km values of 24 microM for NADPH and 16 microM for cytochrome c. An in vitro
      reconstituted system of the purified reductase with a partially purified tobacco
      cytochrome P-450 preparation showed the cinnamic acid 4-hydroxylase activity at
      the rate of 14 pmol min-1 nmol-1 P-450 protein and with a purified rabbit P
      4502C14 catalyzed N-demethylation of aminopyrine at the rate of 6 pmol min-1 nmol
      1 P-450 protein. Polyclonal antibodies raised against the purified reductase
      reacted with tobacco reductase but not with yeast reductase on Western blot
      analysis. Anti-yeast reductase antibodies did not react with the tobacco
      reductase. This result indicate that the tobacco reductase was immunochemically
      different from the yeast reductase. The anti-tobacco reductase antibodies totally
      inhibited the tobacco reductase activity, but not the yeast reductase. Also,
      Western blot analyses using the anti-tobacco reductase antibodies revealed that
      leaves, roots and shoots of Nicotiana tabacum plants contained an equal amount of
      the reductase protein. From these results, it was suggested that there are
      different antibody binding sites, which certainly participate in enzyme activity,
      between tobacco and yeast reductase.

PMID- 7811732
TI  - Hemorrhagic principles in the venom of Bitis arietans, a viperous snake. I.
      Purification and characterization.
AB  - Two hemorrhagic principles (Bitis arietans hemorrhagin a and b: abbreviated as
      BHRa and BHRb) were purified from the venom of the viperous snake Bitis arietans
      (puff adder) by gel filtration, ion-exchange and absorption chromatography. A 10
      fold purification was achieved for BHRa and 7-fold for BHRb with an overall yield
      of 6.4% of hemorrhagic activity. The hemorrhagins were homogeneous according to
      disc- and SDS-polyacrylamide gel electrophoresis and immunodiffusion. BHRa and
      BHRb consist of 623 and 685 amino-acid residues and their apparent molecular
      weights were 68,000 and 75,000, respectively. They were also immunologically
      distinct. The purified hemorrhagins express proteolytic activity with heat
      denatured casein and hide powder azure. The proteolytic activity with heat
      denatured casein was almost the same as that of the crude venom, but that with
      hide powder azure was less than one-tenth of that of the crude venom. The
      purified hemorrhagins were free of arginine esterase and phospholipase A2
      activities and they are acid labile hemorrhagic toxins. Their hemorrhagic
      activity was inhibited by EDTA, cysteine and by polyvalent anti-snake serum, but
      not by phenylmethanesulfonyl fluoride or soybean trypsin inhibitor.

PMID- 7811733
TI  - Residues affecting the catalysis and inhibition of rat lens aldose reductase.
AB  - Aldose reductase (AR), the first enzyme of the polyol pathway, has been
      implicated in diabetic complications. Results of recent clinical studies have
      shown that compounds that inhibit aldose reductase (ARIs) and block the flux of
      glucose through the polyol pathway have provided benefit to diabetic neuropathic
      patients. Since many ARIs show broad substrate specificity, emphasis on the
      structure-function properties of the AR enzyme will help in the refinement and
      design of future inhibitors. To this end, catalysis and inhibition of rat lens
      aldose reductase was examined following site-directed mutagenesis. Replacement of
      tyrosine 48 with phenylalanine (Y48F) resulted in an enzyme form with less than
      0.25% activity with DL-glyceraldehyde and no detectable activity with p
      nitrobenzaldehyde or xylose, although circular dichroism spectra and NADPH
      binding affinity were similar to wild-type AR. Mutation of histidine 110 to
      glutamine (H110Q) also resulted in a less active protein with an approximate 3
      fold decrease in kcat for the reduction of DL-glyceraldehyde; slight or no
      activity was measured with other substrates and an increase of 195-fold over wild
      type was observed in the Km for glyceraldehyde. H110Q was less sensitive to
      inhibition by aldose reductase inhibitors. The most dramatic change was seen with
      imeristat, which showed an 1800-fold increase in IC50. Mutation of cysteine 298
      to serine (C298S) affected enzyme function by increasing kcat 2- to 4-fold and
      increasing Km 15- to 48-fold, with DL-glyceraldehyde, p-nitrobenzaldehyde or
      xylose as substrates. As a result kcat/Km, catalytic efficiency, dropped to
      approx. 10% of control. Inhibition of C298S was not noticeably different from
      wild type. Substitution of histidine 187 or 200 with glutamine (H187Q, H200Q) had
      little effect on AR catalysis or inhibition. Based on structural and mutagenesis
      studies of human AR and the conservation of amino acids between human and rat,
      these data would indicate that Y48, H110, and C298 are important residues in the
      active site of rat AR and that Y48 is most likely the proton donor during
      substrate reduction by rat lens aldose reductase. In addition, these studies
      indicate that mutagenesis of H110 also affects aldose reductase inhibition.

PMID- 7811734
TI  - The reactivity of thiol compounds with different redox states of leghaemoglobin:
      evidence for competing reduction and addition pathways.
AB  - Reaction of the ferric form of leghaemoglobin with hydrogen peroxide has been
      previously shown to give rise to an iron(IV)-oxo (ferryl) species, and a protein
      radical. Inclusion of a variety of thiol compounds in this system is shown to
      lead to rapid loss of the iron(IV)-oxo species and the regeneration of the ferric
      form and/or the formation of novel sulf species formed by nucleophilic attack of
      the thiol group on the tetrapyrrole ring. The reduction process also results in
      the generation of thiyl radicals which have been detected by EPR spin trapping.
      The relative yields of the products produced by these two competing pathways is
      shown to be highly dependent on the steric and electronic characteristics of the
      thiol compound. Evidence has also been obtained, in the absence of hydrogen
      peroxide, for both the reduction of the ferric form of the protein to the oxy
      ferrous form, via a process believed to involve the deoxy-ferrous species, and
      the formation of sulf-leghaemoglobin species. Both of these pathways are again
      highly dependent on the structure of the thiol, and the former also results in
      the generation of thiyl radicals. Inclusion of the sulfide anion in place of the
      organic thiols results in somewhat different behaviour, in that this species
      appears to both reduce the iron centre and form a complex with the iron atom.
      This ligation process is reversible, and the sulfide complex is shown to react
      readily with both strong oxidizing and reducing agents. The behaviour of this
      protein, which is structurally related to myoglobin, is dramatically different to
      that demonstrated by myoglobin; this is rationalized in terms of the much more
      open heme site of leghaemoglobins, and the presence of an electronic gate which
      hinders access by negatively charged molecules. The contribution of these
      processes to the maintenance of the leghaemoglobin proteins in the oxy-ferrous
      form in vivo and the binding of oxygen is discussed.

PMID- 7811735
TI  - 13C-NMR off-resonance rotating frame spin-lattice relaxation studies of bovine
      lens gamma-crystallin self association: effect of 'macromolecular crowding'.
AB  - The NMR technique of 13C off-resonance rotating frame spin-lattice relaxation,
      which provides an accurate assessment of the effective rotational correlation
      time (tau 0, eff) for macromolecular rotational diffusion, was applied to the
      study of gamma-crystallin association as a function of protein concentration and
      temperature. Values of the effective rotational correlation time for gamma
      crystallin rotational diffusion were obtained at moderate to high protein
      concentrations (80-350 mg/ml) and at temperatures above, and below, the cold
      cataract phase transition temperature. With increasing concentration gamma
      crystallin was observed to increasingly associate as reflected by larger values
      of tau 0, eff Decreasing temperature in the range of 35 to 22 degrees C was found
      to result in no change in the temperature corrected value of tau 0, eff at a
      gamma-crystallin concentration of 80 mg/ml, whereas at temperatures of 18 degrees
      C or below, this parameter was approx. twofold larger, suggesting the occurrence
      of a well defined phase transition, which correlated well with the cold cataract
      phase transition temperature. At higher protein concentrations, by contrast, tau
      0, eff (temperature corrected) was found to increase by approx. 1.6- to 2-times
      in the temperature interval 35 degrees C to 22 degrees C, a result consistent
      with the dependence of the cold cataract phase transition temperature on gamma
      crystallin concentration. Analysis of intensity ratio dispersion curves, using an
      assumed model of isodesmic association, permitted the estimation of the
      association constant characterizing the aggregation under particular conditions
      of concentration and temperature. The significant increase in the value of the
      association constant with moderate increases in protein concentration was
      rationalized by invoking the effect of 'macromolecular crowding'. The results
      obtained in this study suggest that in the intact lens, where high protein
      concentrations prevail, gamma-crystallin is unlikely to be found in the monomeric
      state, but more likely, as a significantly aggregated species, representing a
      broad molecular weight distribution.

PMID- 7811737
TI  - The 'Iceman': molecular structure of 5200-year-old skin characterised by Raman
      spectroscopy and electron microscopy.
AB  - The molecular state of about 5200-year-old skin from the so-called 'Iceman'
      (Similaun man or Otzi) has been characterised using Fourier transform Raman
      spectroscopy, and has been compared with that of contemporary man. Contemporary
      skin was also freeze-dried (to mimic the conditions under which the ancient skin
      was preserved) and its molecular structure was compared with that of Iceman skin.
      The results showed that the proteinaceous moiety of the ancient skin had degraded
      considerably and, although olefinic bonds had probably oxidised, the lipoidal
      component was largely unaltered. Electron microscopical comparisons of Iceman and
      contemporary skin showed that the gross structure of Iceman skin had survived
      essentially intact for five millennia.

PMID- 7811736
TI  - Interaction of ATP and lens alpha crystallin characterized by equilibrium binding
      studies and intrinsic tryptophan fluorescence spectroscopy.
AB  - alpha-Crystallin, the most prevalent protein in vertebrate lenses, is a high
      molecular weight aggregate composed of alpha A and alpha B subunits. Evidence is
      presented that ATP, a major phosphorus metabolite of the lens binds to alpha
      crystallin extracted from calf lenses. The following parameters were obtained
      from equilibrium binding studies conducted at 37 degrees C: binding sites per 400
      kDa aggregate = 10 and Ka = 8.1 x 10(3) M-1; and an essentially identical Ka of
      7.84 x 10(3) M-1 and 22 binding sites were determined for a 850 kDa aggregate.
      The cooperativity parameter, alpha H, approximates unity which denotes that the
      binding of ligand is at independent sites. Binding was not significant at 22
      degrees C and was absent at 4 degrees C. The specificity of the binding site for
      ATP was established by intrinsic tryptophan fluorescence spectroscopy. In the
      presence of increasing concentrations of ATP (0.05-0.3 mM), tryptophan
      fluorescence decreases in a concentration dependent manner to a minimum of 0.2 mM
      above which there is a non-linear response. Quenching of fluorescence was not
      evident with P(i), AMP or ADP. GTP elicited a minimal quenching of fluorescence
      only at the highest concentration (0.30 mM). Modulation of both supramolecular
      organization and lens metabolism is predicted as a consequence of ATP/alpha
      crystallin binding.

PMID- 7811738
TI  - Hydrolysis of DMPC or DPPC by pancreatic phospholipase A2 is slowed down when
      (perfluoroalkyl) alkanes are incorporated into the liposomal membrane.
AB  - The effect of the incorporation of linear (perfluoroalkyl)alkanes (CmF2m + 1CnH2n
      + 1, FmHn) into liposomes made of DMPC or DPPC on the activity of porcine
      pancreatic phospholipase A2 was investigated. A large decrease in enzyme activity
      and modifications of the kinetic profile, especially at and above the
      phospholipid's phase transition temperature, were observed; both depend on the
      relative lengths of the phospholipid's fatty acid chains and of the Hn segment of
      the FmHn molecule. With DMPC Hn must have a minimum of 10 carbon atoms to be
      effective, as in F6H10, F8H10 and F4H12; F8H8 had no significant hydrolysis-rate
      reducing effect. With DPPC Hn must have a minimum of 12 carbon atoms, as in
      F4H12, while F8H8, F6H10 and F8H10 were ineffective. The absence of effect when
      C10H22 or C16H34 was incorporated establishes that the fluorinated segment,
      although its length (from C4 to C8) is not crucial, is required to hinder
      hydrolysis by PLA2, indicating that this segment plays an important role in
      structuring the liposomal membrane.

PMID- 7811739
TI  - Different effects of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors
      on sterol synthesis in various human cell types.
AB  - The three vastatins examined, lovastatin, simvastatin and pravastatin, are
      equally strong inhibitors of the sterol synthesis in human hepatocytes in culture
      with IC50-values of 4.1, 8.0 and 2.0 nM, respectively. However, in the human
      extrahepatic cells: umbilical vascular endothelial cells, retinal pigment
      epithelial cells, cornea fibroblasts and granulosa cells, pravastatin was much
      less inhibiting the sterol synthesis than lovastatin or simvastatin. It was
      observed as well that longer incubation with the vastatins resulted in higher
      IC50-values. In order to show that the feedback regulation mechanism for 3
      hydroxy-3-methylglutaryl-coenzyme A reductase was involved in this phenomena mRNA
      levels were measured in human vascular endothelial cells after incubation with
      the vastatins for 3.5 h and for 20 h. Indeed, lovastatin and simvastatin gave
      rise to higher levels of HMG-CoA reductase mRNA after 20 h than after 3.5 h of
      incubation. The differences observed in different human cell types can be
      explained by supposing that pravastatin is transported into the human hepatocyte
      via a liver-specific transporter. This was supported by the results of uptake
      experiments with 14C-labelled pravastatin and 14C-labelled simvastatin into human
      hepatocytes compared to that into human umbilical endothelial cells (as an
      example of an extrahepatic cell type). [14C]-Simvastatin was associated with both
      cell types, whereas [14C]-pravastatin was hardly associated with human
      endothelial cells, but to a similar extent as [14C]-simvastatin with human
      hepatocytes.

PMID- 7811740
TI  - Cloning and characterization of a murine macrophage lipoxygenase.
AB  - We have isolated a murine macrophage cDNA encoding a 12-lipoxygenase, that
      represents the homolog of the human 15-lipoxygenase. The predicted amino acid
      sequence of this lipoxygenase is highly similar to the rat 12-lipoxygenase
      isolated from brain and human 15-lipoxgenase. The recombinant enzyme expressed in
      Cos-7 cells oxidizes arachidonic acid to 12- and 15-HETE with a profile similar
      to that obtained from peritoneal macrophages. A polyclonal antibody generated
      against a putative peptide recognizes a 75 kDa protein in cell extracts from
      mouse peritoneal macrophages and transfected Cos-7 cells. The lipoxygenase cDNA
      hybridizes to a 2.5 kb mRNA present in peritoneal macrophages, lung, spleen,
      heart and liver. RT-PCR analysis indicates that the same lipoxygenase is
      expressed in mouse reticulocytes. A partial genomic clone for this lipoxygenase
      has also been characterized. Southern blot analysis of mouse genomic DNA
      indicates that this is a single copy gene.

PMID- 7811741
TI  - Plasma factors affecting the in vitro conversion of high-density lipoproteins
      labeled with a non-transferable marker.
AB  - We studied the in vitro conversion of HDL3 labeled with a radioiodinated diacyl
      lipid associating peptide (diLAP). DiLAP was previously shown to be
      nontransferable, which permitted its' use as a reliable marker of HDL particles.
      DiLAP-labeled HDL3 was incubated for 23 h at 37 degrees C in human or rat plasma
      or in reconstituted media containing delipidated plasma and/or lipoproteins
      and/or partially purified CETP. At the end of the incubations, the samples were
      adjusted to a density of 1.125 g/ml and ultracentrifuged. The two resulting
      fractions containing HDL2 and HDL3, respectively, were analyzed by gradient gel
      electrophoresis. Depending upon experimental conditions, diLAP-labeled HDL3 was
      converted into HDL2b- and/or small HDL3c-like particles. LCAT inhibition and to a
      lesser extent CETP promoted the formation of small HDL3c. Reactivation of LCAT
      led to the disappearance of small HDL3c. No HDL3c formed from HDL2 even in the
      absence of LCAT activity. When the incubations were performed in the presence of
      100 mM thimerosal, which inhibited PLTP but not CETP activity, the conversion of
      diLAP-labeled HDL3 into HDL2 was almost completely blocked. Collective
      consideration of these data indicates that the formation of small HDL is
      moderately facilitated by CETP; that small HDL are converted to larger HDL
      species by LCAT and that the transformation of HDL3 into HDL2 is a process which
      largely depends upon PLTP activity.

PMID- 7811742
TI  - Visualization of lateral phases in cholesterol and phosphatidylcholine monolayers
      at the air/water interface--a comparative study with two different reporter
      molecules.
AB  - This study has compared two chemically distinct NBD-lipids with regard to their
      partitioning properties into lateral phases of pure and mixed
      cholesterol/phosphatidylcholine monolayers. Pure NBD-cholesterol (22-(N-(7
      nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-23,24-bisnor++ +-5-cholen-3-ol), which has
      the NBD-function in the sterol side chain (at carbon 22), gave a liquid-expanded
      force-area isotherm on water at 22 degrees C (having a compressibility of 0.005
      to 0.007 m/mN), although epifluorescence microscopy of the compressed NBD
      cholesterol monolayer revealed that it had a solid-like surface texture. When the
      compressed NBD-cholesterol monolayer was allowed to expand, it fragmented into
      large flakes (tens to hundreds of microns in width) which eventually dissolved
      into a liquid state. The force-area isotherm of pure NBD-phosphatidylcholine (1
      hexadecanoyl-2-(12-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)dod ecyl-sn- glycero
      3-phosphocholine) was also liquid-expanded. When a compressed (30 mN/m) monolayer
      of NBD-phosphatidylcholine was examined by microscopy, it displayed many bright
      crystalline spots (about 50 microns across) which appeared to form when the
      monolayer was allowed to stabilize at this lateral surface pressure. These bright
      spots disappeared when the monolayer was expanded. When the surface texture of a
      pure cholesterol monolayer was examined, both probes (at 1 mol%) partitioned very
      similarly in the sterol monolayer. At low lateral surface pressures (1 and 5
      mN/m) the probes appeared to be excluded from the cholesterol phase, forming very
      bright liquid-like areas against a uniformly black cholesterol phase. At 30 mN/m,
      NBD-phosphatidylcholine appeared to distribute increasingly into the cholesterol
      phase, whereas NBD-cholesterol still did not to mix with cholesterol. The
      characteristic surface texture of the liquid-expanded to liquid-condensed lateral
      phase transition of pure dipalmitoyl phosphatidylcholine (DPPC) monolayers could
      be visualized identically with both probes, indicating that these were similarly
      excluded from the liquid-condensed solid phase of DPPC. Finally, in mixed
      monolayers containing cholesterol and DPPC (molar ratio 33:67), both probes (at 1
      mol%) revealed a similar surface texture of the monolayers (examined at a lateral
      surface pressure of 0.5 mN/m), suggesting that these partitioned similarly
      between the different lateral phases present in the mixed monolayer. In
      conclusion, although the two NBD-probes differed from each other in chemical and
      physical properties, both acted like 'impurities' when admixed into pure or mixed
      monolayers, and appeared to be equally excluded from lateral phases in which the
      packing density was high.

PMID- 7811743
TI  - Reduced dimerization of lipoprotein lipase in post-heparin plasma of a patient
      with hyperchylomicronemia.
AB  - As in post-heparin plasma of control subjects, post-heparin plasma of a patient
      with hyperchylomicronemia contained lipoprotein lipase (LPL) subunits with M(r) =
      57,000. But although the amount of LPL was the same as in post-heparin plasma of
      controls, no LPL activity was detectable. Nearly all the LPL in post-heparin
      plasma of controls bound to heparin-Sepharose and this LPL bound was mainly
      eluted with 1.5 M NaCl in parallel with the activity. In post-heparin plasma of
      the patient, 58% of the LPL subunits did not bind to heparin-Sepharose and 23%
      was eluted with 0.6 M NaCl. Studies by sucrose density gradient centrifugation
      showed that almost all the LPL in post-heparin plasma of controls was recovered
      in the peak with a sedimentation coefficient of 6.8 S, corresponding to the
      position of a dimeric form of LPL, in parallel with the activity; little LPL was
      recovered in the peak with a sedimentation coefficient of 4.0 S, corresponding to
      the position of a monomeric form of LPL. In post-heparin plasma of the patient,
      35% of the LPL subunits was recovered in fractions with larger sedimentation
      coefficients at the bottom of the centrifuge tube, indicating the presence of an
      aggregated form(s) of LPL; the amount of the monomeric form of LPL was increased,
      while that of the dimeric form was decreased. Thus, defect of LPL activity in
      post-heparin plasma of the patient with hyperchylomicronemia could result from
      reduced dimerization of LPL subunits.

PMID- 7811744
TI  - Evaluation of cultured hamster hepatocytes as an experimental model for the study
      of very low density lipoprotein secretion.
AB  - The secretion of triacylglycerol, cholesterol and cholesteryl ester in very low
      density lipoprotein (VLDL) by cultured hamster hepatocytes was studied, and the
      results compared with those obtained previously using cultured rat hepatocytes
      and the human hepatoma cell line HepG2. The hamster cells secreted apolipoprotein
      B and VLDL triacylglycerol, cholesterol and cholesteryl ester linearly during 24
      h in culture, and this time period was used in all experiments. Addition of
      oleate (1 mM) to the culture medium resulted in increased secretion of
      triacylglycerol, but cholesterol ester output were unchanged. Triacylglycerol
      secretion was also increased in the presence of lipogenic substrates (10 mM
      lactate + 1 mM pyruvate) plus dexamethasone (1 microM), but not with either of
      these agents alone. Inhibition of cholesterol synthesis in the hamster cells by
      incubation with mevinolin (2 micrograms/ml) did not change VLDL lipid secretion,
      but stimulation using mevalonate lactone resulted in decreased triacylglycerol
      output. Manipulation of the rate of cholesterol esterification in the hepatocytes
      by inhibiting or stimulating the activity of acyl coenzyme A cholesterol:acyl
      transferase using the inhibitor Dup128 (25 microM) and 25-hydroxycholesterol (50
      microM), respectively, had no effect on the secretion of VLDL lipid. In the
      presence of 1 mM oleate plus 25-hydroxycholesterol, however, a rise in the output
      of triacylglycerol and cholesteryl ester was observed. Hepatocytes prepared from
      hamsters fed 2% cholestyramine secreted significantly less triacylglycerol than
      those from animals given the control diet, but cholesterol and cholesteryl ester
      output were unchanged, despite a decrease of about 40% in the total cholesterol
      content of the cells. These results show that the secretion of lipid in VLDL in
      hamster hepatocytes differs from that in rat and human liver in its response to
      dietary cholestyramine, and from rat hepatocytes and HepG2 cells in its response
      to changes in the rate of lipogenesis and cholesterol synthesis and
      esterification. Overall, hamster hepatocytes appear to be less susceptible to
      modification the rate of hepatic VLDL secretion, and should provide a useful
      additional tool for the investigation of this process.

PMID- 7811745
TI  - Glycosylation, dimerization, and heparin affinity of lipoprotein lipase in 3T3-L1
      adipocytes.
AB  - The relationship between glycosylation, dimerization, and heparin affinity of
      lipoprotein lipase (LPL) was studied in 3T3-L1 adipocytes. Three forms of LPL
      subunits were found in normal cells; totally endo H-resistant (57 kDa), partially
      sensitive (54 kDa), and totally sensitive (51 kDa) forms. LPL in normal cells was
      active, dimeric, and showed high affinity for heparin. LPL in cells treated with
      tunicamycin, preventing the transfer of N-linked oligosaccharide chain, was
      unglycosylated (51 kDa) and inactive. LPL proteins were found as an aggregate,
      and had low affinity for heparin. After treatment with castanospermine, an
      inhibitor of ER glucosidase I, 80% of LPL activity was inhibited. Most of LPL
      proteins were totally endo H-sensitive, present as an aggregate, and had low
      affinity for heparin. LPL in cells treated with deoxymannojirimycin, an inhibitor
      of Golgi mannosidase I, was active, dimeric, and had high affinity for heparin as
      in normal cells. But LPL subunits were all endo H-sensitive. These results
      suggest that core glycosylation and subsequent removal of glucose residue is
      required, but processing after Golgi mannosidase I is not necessary for
      dimerization and acquisition of high heparin affinity of LPL.

PMID- 7811746
TI  - Cholesterol metabolism in monocyte-derived macrophages from macrophage colony
      stimulating factor administered rabbits.
AB  - The metabolism of beta-very-low-density lipoproteins (beta-VLDL) in macrophages
      from the blood monocytes of rabbits, which had been administered macrophage
      colony-stimulating factor (M-CSF) in vivo, was investigated in order to clarify
      the mechanism of the suppressive effect of M-CSF on cholesterol accumulation in
      macrophages. Cholesterol ester content after incubation with beta-VLDL, and
      [3H]cholesterol oleate-beta-VLDL incorporation remarkably increased in cultured
      macrophages from blood monocytes in the high cholesterol diet control group
      compared to those in the normal diet control group. Those in macrophages from M
      CSF-treated groups, both normal diet and high cholesterol diet, were the same as
      in the normal diet control group. The ratio of released [3H]cholesterol to
      incorporated [3H]cholesterol oleate-beta-VLDL in macrophages from control was
      smaller than that from the M-CSF group. The acyl-coenzyme A:cholesterol
      acyltransferase (ACAT) activity was enhanced in the high cholesterol diet groups,
      and the activity in M-CSF-treated groups decreased. The neutral cholesterol
      esterase activity was enhanced in the M-CSF-treated groups compared with that in
      the non-treated control groups. These results suggest that high cholesterol diet
      induced further cholesterol esterification and that M-CSF treatment enhanced
      cholesterol clearance in macrophages.

PMID- 7811747
TI  - Sequential changes in glycolipid expression during human B cell differentiation:
      enzymatic bases.
AB  - We have previously reported that human B cell differentiation is accompanied by
      sequential changes in glycosphingolipid expression. Pre-B cells contain lacto
      series type II chain-based glycolipids and GM3 ganglioside; mature/activated B
      cells do not synthesize lacto-series compounds but express GM3 and globo-series
      glycolipids (Gb3 and Gb4); terminally differentiated B cells, in addition to
      these compounds, also contain GM2 ganglioside. At the cell surface, Gb3, Gb4 and
      GM2 constitute stage-specific antigens. To elucidate the biosynthetic mechanism
      leading to these modifications we have compared activities of the
      glycosyltransferases involved in the core structure assembly and the first
      elongation steps of neo-lacto, ganglio- and globo-series glycolipids. These
      glycosyltransferase activities have been measured in B cell lines and normal B
      lymphocytes at various stages of differentiation. We first determined the optimal
      requirements of the four glycosyltransferases which synthesize Lc3, GM3, Gb4 and
      GM2 glycolipids in B lymphocytes and then tested these enzymes and the Gb3
      synthetase in the selected B cells. The following results were obtained: beta 1-
      >3 N-Acetylglucosaminyltransferase (Lc3 synthetase) has a high activity in pro-
      and pre-B cells whereas it is undetectable in more differentiated cells; alpha 2-
      >3 sialytransferase (GM3 synthetase) is activated from the pre-B cell stage to
      the terminally differentiated myeloma cells; alpha 1-->4 galactosyltransferase
      (Gb3 synthetase) is only detected in cells representing the late stages of B cell
      differentiation; beta 1-->3 N-Acetylgalactosaminyltransferase (Gb4 synthetase) is
      only found in some lymphoblastoid cell lines, representative of activated B cells
      whereas the beta 1-->4 N-Acetylgalactosaminyltransferase (GM2 synthetase) has a
      high activity in these lymphoblastoid cell lines and in terminally differentiated
      myeloma cells. These results suggest that the sequential shifts in the three
      major glycosphingolipid series observed during B cell differentiation are mostly
      due to sequential activations of the corresponding glycosyltransferases.

PMID- 7811748
TI  - 3,5-Di-t-butyl-4-hydroxytoluene (BHT) and probucol stimulate selectively the
      reaction of mammalian 15-lipoxygenase with biomembranes.
AB  - The lipophilic antioxidant 3,5-di-t-butyl-4-hydroxytoluene (BHT) and the
      structurally-related antiatherogenic drug probucol stimulate the oxygenation of
      mitochondrial membranes and erythrocyte ghosts by the rabbit 15-lipoxygenase as
      indicated by an increase in oxygen consumption as well as by an enhanced loss of
      polyenoic fatty acids and by the formation of specific lipoxygenase products in
      the membrane phospholipids. The oxygenation of linoleic acid, phospholipids and
      human low-density lipoproteins was not stimulated. With mitochondrial membranes,
      BHT causes a quenching of the 1-anilino-8-naphthalene sulfonate fluorescence.
      Thus, it is suggested that the stimulation of membrane oxygenation may be due to
      structural changes in the membranes leading to a better susceptibility of the
      polyenoic fatty acid residues towards lipoxygenase attack. Owing to this
      unexpected effect of the antioxidants, which is not related to their radical
      scavenger capacity, care should be taken in interpreting experimental data on
      effects of BHT and probucol.

PMID- 7811749
TI  - The mechanism of lack of hypocholesterolemic effects of pravastatin sodium, a 3
      hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, in rats.
AB  - In order to clarify the reason why pravastatin, a 3-hydroxy-3-methylglutaryl
      (HMG)-CoA reductase inhibitor, did not show hypocholesterolemic effects in rats,
      the changes of various parameters affecting the serum cholesterol levels by
      pravastatin were determined in rats and rabbits, as a comparison. In rabbits,
      pravastatin administration at 50 mg/kg for 14 days decreased serum and liver
      cholesterol by 40% and 8%, respectively. The hepatic LDL receptor activity was
      increased 1.7-fold, and VLDL cholesterol secretion was decreased. Cholesterol 7
      alpha-hydroxylase activity was not changed. In contrast, in rats, serum
      cholesterol was increased by 14% at 50 mg/kg and 27% at 250 mg/kg for 7 days,
      respectively. At 250 mg/kg, liver cholesterol was significantly increased by 11%.
      Under these conditions, neither the hepatic LDL receptor activity nor cholesterol
      7 alpha-hydroxylase was changed, and VLDL cholesterol secretion was increased. At
      250 mg/kg, net cholesterol synthesis in rat liver was increased after 7 days of
      consecutive administration. These results imply that in rats, stimulated net
      cholesterol synthesis caused the increase of liver cholesterol followed by the
      increase of VLDL cholesterol secretion, and resulted in the raise of plasma
      cholesterol. Although hepatic HMG-CoA reductase was induced almost the same fold
      in both animals at 50 mg/kg, the induced HMG-CoA reductase activity in rats might
      overcome the inhibitory capability of pravastatin, resulting in an increase of
      net cholesterol synthesis, but not in rabbits. This over response to pravastatin
      in rats might cause the lack of hypocholesterolemic effects of this drug.

PMID- 7811751
TI  - Very fast ultracentrifugation of serum lipoproteins: influence on lipoprotein
      separation and composition.
AB  - A very short run time and small sample volumes in the separation of lipoproteins
      by preparative ultracentrifugation are needed for several investigations.
      Recently, a very fast sequential separation method was described that needs only
      100 min for one run in a centrifugal field of 625,000 x g. We studied the
      influence of centrifugal fields of this dimension on lipoprotein separation and
      lipoprotein particle integrity using a Beckman Optima TLX ultracentrifuge with a
      TLA-120.2 rotor. Rotor speed (120/90/60/30.10(3) rev./min) and run time (100
      min/3 h/6.7 h/27 h) were selected in such a way that the product of centrifugal
      field and run time remained constant. The first conditions correspond to the very
      fast ultracentrifugation (VFU) procedure with a centrifugal field of 625,000 x g.
      Thirty different plasma samples covering a wide range of lipid and protein
      concentrations were separated in the course of two centrifugal runs at densities
      of 1.006 and 1.063 kg/l which yielded very-low-density lipoproteins (VLDL), low
      density lipoproteins (LDL), and the subnatant of low-density lipoproteins,
      including high-density lipoproteins (HDL) and concomitant sedimented plasma
      proteins. The major lipid components of the lipoproteins, triacylglycerols, free
      and esterified cholesterol, phospholipids and the apolipoproteins B and A-I, were
      estimated considering the masses of the tube contents after a slicing procedure.
      Measurements of lipids and proteins showed a very good recovery of better than
      94% and 91%, respectively, and precision-within-series (coefficient of variation)
      of better than 4.2% and 6.5%, respectively. The effects of the rotor speed on the
      lipoprotein structure appeared to be weak. With increasing rotor speed, VLDL and
      LDL lipid constituents principally tended to decrease, whereas they increased in
      the subnatant of the LDL-run. The mean lipoprotein mass composition, considering
      the mass percentage of each measured particle constituent, did not show
      significant alterations. Total protein decreased in VLDL and in LDL and increased
      in the subnatant of the LDL-run. As checked by an enzyme-linked immunosorbent
      assay (ELISA) and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS
      PAGE), the protein effects were due to nearly complete disappearance of
      contaminating plasma proteins, especially albumin as the major contamination of
      VLDL and LDL. The apolipoproteins (apo) B-100, A-I, E and C-I to C-III remained
      nearly unaffected. The main advantages of VFU were the very short run time
      (cumulative flotation time is 3.4 h) and the elemination of albumin without
      repeated runs. The procedure was suitable for the assessment of lipid and protein
      constituents in lipoproteins from very small plasma samples (500 microliters).

PMID- 7811750
TI  - Methylation of the beta-positions of the furan ring in F-acids.
AB  - Major incubation products in feeding experiments with the sodium salt of 7-(5
      butyl-furan-2-yl)heptanoic acid (3) on suspension cultures of Saccharum spec. are
      the unusual F-acids (4a) and (4b). They possess in contrast to natural monomethyl
      substituted F-acids a methyl substituent in the 4-position of the furan ring.
      Unexpectedly, the dimethyl substituted F-acids (4c) and (4d) were found only in
      very small amounts. The detection and structure elucidation of the methylation
      products (4a)-(4d) was achieved predominantly by GC-MS analysis of the
      corresponding tetrahydrofuran derivatives (5a)-(5d).

PMID- 7811752
TI  - Influence of bile salt molecular species on cholesterol crystallization from
      supersaturated model biles.
AB  - Time-sequential enzymatic determination of cholesterol (CH) crystals harvested by
      ultrafiltration, and concomitant polarizing light microscopy observations
      corroborated the striking importance of the bile salts (BS) species in
      determining CH crystals formation rate from supersaturated model biles incubated
      in vitro. The more hydrophilic tauroursodeoxycholate, taurohyocholate,
      glycohyocholate, taurohyodeoxycholate, glycohyodeoxycholate and glyco-3 alpha,
      hydroxy-6 oxo-5 beta-cholanate inhibited CH precipitation through the formation
      of a stabilized liquid-crystalline phase. In contrast, in all hydrophobic systems
      (taurine (T) and glycine (G) conjugates of cholate (C), deoxycholate (DC) and
      chenodeoxycholate (CDC)), CH crystals precipitated with time. When crystallized
      CH concentrations were plotted vs. time, the figures showed a sigmoidal pattern,
      consistent with the transition from metastable systems to stable equilibrium
      states. Over the equilibration period, the nucleation kinetics (as inferred from
      enzymatic measurements) and all crystallization events (as microscopically
      observed) were both shifted in time, depending on the BS species: they were
      earliest in CDC systems, then in DC systems, and finally in C systems. In the
      latter, the delay was clearly due to the formation of a transient labile liquid
      crystalline phase. G-conjugation also induced a significant delay in CH
      precipitation, compared to T-conjugation. At last, maximum crystallized CH
      concentrations at equilibrium were in the decreasing order: C > CDC > DC and T
      conjugates > G-homologues. All data are discussed in connection with BS
      hydrophobicities, with predictions from the phase equilibria of aqueous biliary
      lipid systems and with new insights into CH crystal habits.

PMID- 7811753
TI  - Certain properties of isoniazid inhibition of mycolic acid synthesis in cell-free
      systems of M. aurum and M. avium.
AB  - In Mycobacterium tuberculosis isoniazid (INH)-susceptibility and the presence of
      a thermolabile catalase-peroxidase (T-catalase) are nearly always associated. It
      is shown in this study that an INH-susceptible strain of M. aurum had a T
      catalase activity while its resistant mutants did not, but an in vitro
      susceptible strain of M. avium had a strong catalase activity without any
      detectable peroxidase properties. Synthesis of mycolic acids is a genus-specific
      target for INH and there is an excellent parallelism between INH-susceptibility
      of intact cells and that of a cell-free system synthesizing mycolic acids. We
      investigated whether the INH-inhibition of mycolic acid cell-free synthesis was
      dependent on a T-catalase activity in M. aurum and M. avium: no catalase activity
      was detectable in any of the cell-free systems tested, and addition of T-catalase
      from susceptible M. aurum strain to an INH-resistant system did not render it
      sensitive. So INH can inhibit mycolic acid synthesis independently of the
      presence of a T-catalase. An INH-susceptible cell-free system prepared from INH
      treated (at the MIC) cells was progressively and irreversibly inhibited, while
      incubation of the same susceptible system in the presence of INH did not result
      in a significant irreversible inhibition. The possible participation of T
      catalase in the irreversible effect of INH is discussed.

PMID- 7811754
TI  - Analysis of nucleotides and oligonucleotides immobilized as self-assembled
      monolayers by static secondary ion mass spectrometry.
AB  - Nucleic acid constituents can be bound to a metal surface in the form of self
      assembled monolayers. Binding is achieved either through ionic interactions with
      a self-assembled 2-aminoethanethiol monolayer or by direct covalent binding of a
      dithiophosphate oligonucleotide to a metal surface through a sulfur-metal bond.
      Nucleotides, polynucleotides (both normal and a dithiophosphate analog) and
      double-stranded DNA have all been bound to surfaces. When the surfaces are
      interrogated using static secondary ion mass spectrometry (SIMS), the surface
      bound nucleic acid constituents are observed in the form of the characteristic
      protonated nucleic acid base ions (BH2+). While a silver foil substrate was found
      to provide the highest absolute signal, vapor-deposited gold yields the best
      signal-to-noise ratio for ionically bound deoxyguanosine monophosphate. Under
      comparable conditions, a Cs+ projectile produces a 10-fold increase in the
      secondary ion signal relative to a Ga+ projectile. The experiment has been
      extended to a triple-quadrupole instrument where tandem mass spectrometric
      experiments on ionically immobilized dGMP showed the characteristic loss of
      ammonia from the released BH2+ ion. When a 'biomimetic' surface formed by
      ionically immobilizing double-stranded DNA is exposed to a solution containing
      ethidium bromide, ions corresponding to the non-covalent adduct are readily
      detectable using SIMS. This adduct and the nucleic acid constituents can be
      monitored at levels below 10 fmol.

PMID- 7811755
TI  - Optimization of the analytical performance of the magnetic sector mass
      spectrometer for the identification of residual chloramphenicol in shrimp.
AB  - Chemical noise limits mass spectrometric detection of chloramphenicol (CAP) with
      electron capture ionization at low resolution, and makes CAP identification at
      concentrations of 5 parts per billion (ppb) difficult. Increasing the resolution
      from 1000 to 3500, however, was sufficient to separate the analyte signals from
      the noise signals, and resulted in a 100 times higher analytical sensitivity. The
      introduction of sweep gas in the ion source decreased the scattering of the
      quantitative results on average by a factor of 7, and thereby improved the
      precision of the analyses to an acceptable level (CV < 10%). Under such
      conditions, CAP residues of 1.5 and 2.1 ppb in shrimp as determined by electron
      capture gas chromatography/mass spectrometry can readily be identified by
      monitoring four diagnostic ions.

PMID- 7811756
TI  - Rapid identification of specific mutations in the sequence of an enzyme variant
      produced by protein engineering using high-performance liquid
      chromatographic/fast atom bombardment mass spectrometric techniques.
AB  - Unknown, specific mutations in the sequence of an enzyme variant (a Bacillus
      subtilisin protease) produced by protein engineering were identified using High
      performance Liquid Chromatographic/Fast Atom Bombardment Mass Spectrometric
      (HPLC/FAB MS) techniques. The variant and the highly homologous wild-type enzyme
      were treated with CNBr followed by tryptic digestion. The resulting peptides were
      analysed using HPLC/frit FAB MS. The peptides with molecular masses beyond the
      range of the HPLC/MS system under the chosen scanning conditions were collected
      using HPLC and subsequently analysed 'off-line' using static FAB MS. This
      procedure allowed the complete amino acid sequence determination of the variant
      protease using the known amino acid sequence of the wild-type enzyme as
      reference.

PMID- 7811757
TI  - Determination of amino- and amide-15N glutamine enrichment with tertiary
      butyldimethylsilyl derivatives.
AB  - We have developed a simple and rapid method for the selective synthesis of tetra
      tertiarybutyldimethylsilyl (TBDMS) glutamine, which allows the simultaneous
      quantitation of glutamine (2-15N) and (5-15N) isotopic enrichment by selected ion
      monitoring (SIM) gas chromatographic/mass spectrometric analysis. The tetra-TBDMS
      glutamine (4S-gln) has an electron impact mass fragment at m/z 258 that contains
      only the amino-N and larger fragments (e.g., at m/z 545) that have both
      nitrogens. Derivatization with acetonitrile (ACN) and N-methyl-N-(tert
      butyldimethylsilyl)trifluoroacetamide yields primarily tri-TBDMS glutamine (3S
      gln) and quantities of 4S-gln too small to allow accurate SIM and tracer/tracee
      ratio determinations. However, when N,N-dimethylformamide, a more polar aprotic
      solvent, was substituted for ACN and the sample was heated for 30 min at 125
      degrees C, greater than 80% of derivatized glutamine appeared as 4S-gln.
      Derivatized plasma samples that had been mixed with amide- and/or amino-15N
      glutamine and analyzed by SIM demonstrated strong agreement (r > or = 0.998, p =
      0.0001) between theoretical and observed enrichment values for the 4S-gln
      fragments at m/z 258 and 545. Deamidation of glutamine to glutamate is negligible
      during sample processing and analysis. This procedure will facilitate the
      investigation of the specific sources and fates of glutamine amide and amino
      nitrogen as well as stable isotope studies involving amino acid transamination,
      ammonia clearance, urea production and other areas of nitrogen metabolism.

PMID- 7811758
TI  - Quantitation of the tetrachloroethylene metabolite N-acetyl-S
      (trichlorovinyl)cysteine in rat urine via negative ion chemical ionization gas
      chromatography/tandem mass spectrometry.
AB  - A sensitive and selective negative ion chemical ionization gas
      chromatographic/tandem mass spectrometric (NICI GC/MS/MS) method was developed
      for the determination of the tetrachlorethylene metabolite, N-acetyl-S
      (trichlorovinyl)cysteine (TCVC), in rat urine. Urine samples were fortified with
      a 13C,D2-analog of TCVC, acidified and extracted with ethyl acetate. The extract
      were derivatized with methanolic HCl, and the resulting methyl esters analyzed
      via NICI GC/MS/MS. Detection of the TCVC analogs was performed by monitoring the
      Cl- product ion of M-Cl2C2HS-. The limit of detection for TCVC by this method was
      estimated to be 0.1 ng ml-1 urine (3 x noise). The quantitation limit was
      determined to be 0.3 ng TCVC per milliliter of urine. The method was found to be
      linear for TCVC concentrations from 0.3 to 104 ng ml-1 urine. Relative recovery
      of TCVC from urine ranged from 95.4% to 108.5%. Additional data are given for
      GC/MS and GC/MS/MS analysis of the pentafluoro-benzyl ester derivative of TCVC.
      Data are also presented for the isolation and analysis of this compound obtained
      from dosed rats.

PMID- 7811759
TI  - Fast atom bombardment mass spectrometry of some lantibiotics.
AB  - Four lantibiotics namely epidermin, gallidermin, lanthiopeptin and mersacidin,
      have been studied by fast atom bombardment mass spectrometry. The molecular ion
      clusters of these compounds can be detected with reasonable abundance. The low
      mass regions of the spectra show the presence of ions characteristic of the amino
      acids in the peptides. The mass distribution of the sequence ions provides
      information about the location of sulphur bridges the occurrence of which is a
      common feature of these kinds of molecules. The two isomeric compounds epidermin
      and gallidermin differ only in a leucine/isoleucine exchange at position 6. These
      two compounds can be distinguished on the basis of the tandem mass spectrum of
      m/z 86, the immonium ion of leucine and isoleucine.

PMID- 7811760
TI  - Charge state specific facile gas-phase cleavage of Asp 75-Met 76 peptide bond in
      the alpha-chain of human apohemoglobin probed by electrospray ionization mass
      spectrometry.
AB  - Herein, we present the first example of charge state specific facile gas-phase
      cleavage of an aspartic acid-methionine peptide linkage. This cleavage (Asp 75
      Met 76) was observed in the alpha-chain of human adult hemoglobin (Hb) and was
      probed by electrospray ionization mass spectrometry. This specific conformational
      and/or charge density dependent dissociation was observed primarily in the [M +
      11H]11+ and [M + 12H]12+ species. A mechanism involving an intramolecular proton
      transfer from the protonated carboxyl side chain of Asp 75 to the neighboring Met
      76 residue yielding an anhydride moiety at the C-terminal of the Asp 75 is
      proposed. Dramatic differences in dissociation of [M + 13H]13+ and [M + 14H]14+
      species were observed.

PMID- 7811761
TI  - Multiple p53 protein isoforms and formation of oligomeric complexes with heat
      shock proteins Hsp70 and Hsp90 in the human mammary tumor, T47D, cell line.
AB  - At least eleven isoforms of p53 protein were observed in a human mammary tumor
      cell line. T47D. Comparative 33P and 35S incorporation analysis showed an equal
      distribution of P53 isoforms within cytoplasmic and nuclear compartments,
      although phosphorylation was unequal among isoforms and the most basic p53
      species was unphosphorylated. Using a combination of immunoprecipitation with
      monoclonal antibodies for p53 and heat shock proteins Hsp70 & Hsp90, and two
      dimensional gel electrophoretic analysis, T47D p53 protein oligomers were
      observed with several species of Hsp70 and Hsp90. The p53/Hsp70/Hsp90 aggregate
      dissociates after nuclear translocation. Immunoprecipitation of Hsp70 and Hsp90
      using monoclonal antibodies showed formation of a heteroligomer between Hsp70 and
      Hsp90 in cytoplasm but not nucleus. This suggests these Hsp proteins can form a
      complex in the cytoplasm but undergo a conformational change after nuclear
      translocation such that Hsp/Hsp binding sites are no longer recognized. These
      data indicate T47D cells have multiple p53 precursor molecules probably at
      different stages of phosphorylation, and which may be sequestered from proteases
      by binding to Hsp proteins. Hsp proteins also can heterocomplex in the cytoplasm,
      also possibly as protection against protease degradation until bound to p53.
      After translocation, p53 is freed from Hsp proteins for binding to DNA where
      Hsp70 and Hsp90 are no longer able to form a nuclear complex probably rendering
      Hsp's labile to proteolysis.

PMID- 7811762
TI  - A classification of one-dimensional electrophoresis gels using wave packet
      decomposition.
AB  - A classification of one-dimensional electrophoresis gels was achieved using a
      fast approximation of the Karhunen-Loeve transformation. The algorithm was based
      on wave packet decomposition theory, using in particular quadrature mirror
      filters derived from orthogonal bases of wavelets. Bacterial proteins from two
      different species of staphylococci were separated by SDS-PAGE electrophoresis.
      The gel images were analyzed by computer and the protein bands were clustered,
      after an orthogonal projection onto a space of lower dimension, by standard
      statistical methods.

PMID- 7811763
TI  - Analysis of snake venoms by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis and two-dimensional electrophoresis.
AB  - The protein composition of snake venom has been analyzed by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and high resolution two
      dimensional electrophoresis (2-DE) with comparison of our simplified
      Tris/glycine/SDS (TGS) method with a commercial Tris/Tricine/SDS (TTS) gel
      system. SDS-PAGE suggests differences between species and similarities between
      related species but 2-DE indicates that the protein composition of the venoms is
      highly complex. The TTS system improves resolution upon 2-DE but our simplified
      TGS method is optimal for silver staining which, contrary to previous reports,
      enhances detection 100-fold.

PMID- 7811764
TI  - Poly(ADP-ribose) polymerase in HeLa cells--a high resolution two-dimensional gel
      analysis.
AB  - PADPRP is an eukaryotic enzyme responsible for poly(ADP-ribosyl)ation of several
      chromatin-associated proteins. Consequently, the modified proteins acquire
      various lengths of negatively charged, covalently bound oligo or poly(ADP
      ribosyl) homopolymers. The present study was undertaken to get an insight into
      the charge and size heterogeneity of the various auto-modified species of PADPRP
      and other protein acceptors of (ADP-ribose) polymers. Toward this end, we
      analyzed HeLa cells using high resolution two-dimensional gel electrophoresis (2D
      PAGE). Resolution of HeLa total cellular lysates in the basic pH range combined
      with immunoblots and activity-blots revealed extensive modification and
      processing of the enzyme. In addition to the native enzyme, a protein of
      approximately 116 kDa, we observed several proteins that exhibit immunoreactivity
      to an antibody prepared against a peptide encompassing the N-terminal 20 amino
      acids of the polymerase. Several protein species showed auto-modifying potential
      in an in situ activity blot assay. We have also localized the ADP-ribosylated
      proteins in permeabilized HeLa cells to demonstrate protein acceptors of poly(ADP
      ribose).

PMID- 7811765
TI  - Characterization of gene expression in the cerebral cortices of rat brains
      containing subcortical lesions.
AB  - Neurotoxic lesion of the nucleus basalis of Meynert in the rat brain, which
      results in the loss of subcortical cholinergic innervation to the cerebral
      cortex, is an animal model for the cortical cholinergic deficits that are
      characteristic of Alzheimer's disease. Previously, we have shown that amyloid
      precursor protein is induced in the cortex in response to this disrupted
      innervation. We have investigated the synthesis and accumulation of proteins in
      lesioned versus control cortices. Total proteins from cortices were separated by
      high resolution two-dimensional gel electrophoresis and visualized by silver
      stain. Of the greater than 1,000 polypeptides examined, only one exhibited a
      consistent alteration in the lesioned sample. This unidentified protein (Mr 34
      kD, pI 5.5) was normally present in scant amounts but was virtually absent in the
      lesioned cortex (0.056% total integrated density (TID) and 0.008% TID,
      respectively; p < 0.04). To investigate gene expression more directly, polysomes
      purified from lesioned and control cortices were assayed in vitro. Examination of
      [35S] incorporation into translation products by two-dimensional gels and
      autoradiography revealed three newly synthesized polypeptide differences in the
      lesioned samples. One protein (M(r) 47 kD, pI 6.1) exhibited elevated levels with
      the lesion (0.05% to 0.16%; p = 0.02) while two other proteins (M(r) 34 kD, pI
      5.5, and M(r) 33 kD, pI 5.7) exhibited reduced levels (0.20% to 0.04%, p < 0.02,
      and 0.34% to 0.12%, p = 0.04, respectively).

PMID- 7811766
TI  - Brief report: electrophoretic separation of oligonucleotides in replenishable
      polyacrylamide-filled capillaries.
AB  - Linear polyacrylamide at concentrations of 8 to 10% seems to be an excellent
      matrix for the electrophoretic separation of oligonucleotides and DNA sequencing
      reactions. However, these solutions, as they are normally prepared, have an
      enormous viscosity and the polymerization must be done within the capillary.
      Based on theoretical considerations, we found that linear polyacrylamide of
      moderate molecular weight and therefore low viscosity could be used instead. We
      show that the separation of oligonucleotides obtained with such solutions is
      comparable to those obtained with in situ polymerization of linear or crosslinked
      polyacrylamide. This method allows easy refilling of the capillaries and might be
      a step towards automation of oligonucleotide analysis and DNA sequencing.

PMID- 7811767
TI  - [Macrolides in the treatment of respiratory infection].

PMID- 7811768
TI  - [Clinical significance of bacteremia caused by streptococci of the viridans
      group].
AB  - BACKGROUND: The viridans group Streptococcus (SVG) include species which may have
      different pathogenic capacity. This study was aimed at evaluating the clinical
      significance of bacteremia by different species of SVG. PATIENTS AND METHODS: One
      hundred ninety-four clinical records of patients with blood culture(s) isolation
      (Hemoline/BioMerieux) of SVG (Api 20 STREP/BioMerieux) over 9 years were reviewed
      with criteria of clinical significance being established and the results analyzed
      by the chi square test. RESULTS: The most frequent species of SVG isolated were:
      S. sanguis II (29.4%), S. mitis (27.3%) and S. anginosus (12.9%). With regard to
      the criteria established, 36% of the isolates were clinically significant,
      associating S. anginosus with significant bacteremia (p = 0.001) and S. mitis
      with non significant bacteremia (p = 0.04). More than half of the isolations of
      S. anginosus, S. bovis, S. mutans and S. adjacens were clinically significant
      with this rate being lower in the remaining species (S. sanguis I, S. sanguis II,
      S. mitis, S. salivarius and S. acidominimus). The significant isolations
      correspond with endocarditis (S. sanguis II being responsible for 44%; p = 0.05).
      In 54.3% of the cases followed by abscesses or other localized infections and
      severe sepsis in patients with a solid or hematologic tumor with a mortality of
      20%. The endocarditis/other disease relation was: greater for the existence of
      endocarditis for S. sanguis II, S. sanguis I, S. mutans, S. bovis and S.
      adjacens; similar in both diseases for S. mitis, and greater for the existence of
      a non endocardic disease for S. anginosus. CONCLUSIONS: In this series the
      isolation of SVG group was clinically significant in 36% of cases with a
      probability of clinical significance and disease association related to the
      species isolated of SVG.

PMID- 7811769
TI  - [Experimental study of bronchofibroscope disinfection].
AB  - BACKGROUND: Fibrobronchoscopes (FB) require high level disinfection following
      each procedure to prevent possible infectious complications. The aim of the
      present study was to evaluate three methods of disinfection of the FB: a)
      aspiration with a solution of iodine povidone (IP); b) immersion in fenolate
      glutaraldehyde (FG) diluted at 1:16, and c) aspiration of IP solution followed by
      immersion in FG. Cleaning of the FB with soap and water was also studied.
      METHODS: The FB was contaminated with artificial samples (sterilized respiratory
      secretions mixed with a suspension of a microorganism at a concentration of 10(8)
      10(9) UFC/ml) and was later washed with soap and water and disinfected with one
      of the 3 above mentioned methods. Samples were taken following contamination,
      cleaning, the aspiration with IP and at 5, 10, 15, 20 and 30 minutes in FG. The
      c/u/ml were counted. Disinfection was considered as a failure with > or = 1
      c/u/ml at the end of each experience. This test was performed 97 times: 37 with
      Mycobacterium tuberculosis, 17 with Serratia marcescens, 17 with Pseudomonas
      aeruginosa, 13 with Staphylococcus aureus, and 13 with Candida albicans. RESULTS:
      Cleaning with soap and water eliminated a mean of 99.9% of the microorganisms. IP
      failed to disinfect all the 5 microorganisms while FG and the association of IP
      and FG failed against S. marcescens and P. aeruginosa. The time of immersion in
      FG required for complete disinfection range from 5 to 20 minutes although in most
      cases only 5 to 10 minutes were needed. CONCLUSIONS: The meticulous cleaning of
      the FB is essential for correct disinfection. Iodine povidone does not guarantee
      high level disinfection of the device while fenolate glutaraldehyde and iodine
      povidone plus fenolate glutaraldehyde may fail versus S. marcescens and P.
      aeruginosa.

PMID- 7811770
TI  - [Identification of yeasts of the Candida genus with a growth inhibition system:
      Microring YT].
AB  - BACKGROUND: It has been observed an spectacular increasing of opportunistic
      Candida yeast infections. Many of them are fatal, and rapid and effective
      identification of the infecting species contributes to start the correct
      treatment. Several new methods for yeast identification have become available;
      Microring YT is one of these methods based on the growth inhibition by 6
      different chemical products. The aim of this work is to study the performance of
      the test using representative clinical yeast isolates. METHODS: A total of 146
      strains belonging to the 5 most common Candida species isolated in the clinical
      laboratory were identified using conventional methods (germ tube and
      chlamydospores production, and the standard API 20C AUX and 16 sugars
      auxonography; Institute Pasteur) and the Microring YT System. This test uses the
      differing susceptibilities of yeast to 6 discs mounted on a filter paper ring.
      The chemical products and dyes are: janus green, ethidium bromide, triphenyl
      tetrazolium chloride, brilliant green, cycloheximide and rhodamine 6G. The
      inhibition pattern of a 6 digit code is compared with a list of profiles.
      RESULTS: Using the Microring YT system 112 of the 146 studied strains were
      correctly identified with an overall concordance of 77% between this method and
      the standard one. The morphological study (germ tube production) increased 6% the
      identification of Candida albicans. Better results were obtained with C. krusei
      and C. parapsilosis (85% of concordance). With C. glabrata only 59% of
      concordance was found. CONCLUSIONS: In spite Microring YT is a simple method,
      easy to perform and read, it was considered inadequate for the identification of
      Candida species as a routine microbiological procedure.

PMID- 7811771
TI  - [Clinicoepidemiologic study of tuberculosis in the Ferrol area (1990-1991)].
AB  - BACKGROUND: To know about the main characteristics of tuberculous disease in our
      county. METHOD: A two-year period (1990-91), retrospective survey of the patients
      diagnosed of tuberculosis at a hospital from the north of La Coruna (Spain) was
      performed. A total of 322 cases were found, 165 diagnosed at the hospital and the
      remaining cases at the clinic. In the latter group, microbiological findings were
      the only diagnostic criteria considered. On the hospital-diagnosed cases three
      diagnostic categories were established: 1) definite; 2) probable, and 3) clinical
      diagnosis. RESULTS: The 1991 annual rate was 73.8 cases/100.000 inhabitants and
      the estimate rate was 80 cases/100.000. On analysis of the hospital-based
      diagnosed subgroup (165 patients), there was a male predominance (112/165), mean
      age was 35 years and 75% of patients were 44-year-old or younger. The most common
      clinical presentation was pulmonary (94 cases), pleural (33 cases) and pleuro
      pulmonary disease (18 cases). Nine patients had concurrent infection with the
      human immunodeficiency virus. There was a culture-proven diagnosis of infection
      by Mycobacterium tuberculosis on 117/165 cases. A total of 115 cases (69.7%)
      received a three-drugs, 9 months therapy. The clinical outcome was fully
      satisfactory in 79/101 patients (78.2%) with a follow-up longer than 6 months.
      Only in one case there was a tuberculosis-related death. CONCLUSIONS: The high
      incidence rate, as well as age distribution and the frequency of pleural disease
      suggest a high tuberculous endemy at our region, over the rates from other parts
      of Spain.

PMID- 7811772
TI  - [Evaluation of blood cultures in anaerobiosis].
AB  - BACKGROUND: The rate of processed blood cultures from anaerobic bottles was
      checked and the number of isolates from anaerobic microorganisms and other non
      anaerobic ones from processed bottles was established. Next, we studied the
      relationship between bacteremia caused by anaerobic organisms and the clinical
      history. METHODS: A total of 3.540 blood cultures have been checked for a period
      of 21 months; all of them were processed using Bactec NR 730 system. Those
      patients suffering bacteremia caused by anaerobic microorganisms had their
      medical histories revised. There is neither Gynecology nor Pediatrics Services at
      our Medical Center. RESULTS: Eleven episodes of bacteremias caused by anaerobic
      microorganisms have been detected since we started our research 21 months ago.
      Three aerobic microorganisms grew only in the two processed bottles in
      anaerobiosis, being their respective aerobic cultures negative. In all cases of
      bacteremia caused by anaerobic bacteria, the clinical history was compatible with
      this infection. CONCLUSIONS: We consider it is worth keeping the anaerobic
      bottles, because the number of anaerobic microorganisms isolates is considerable
      and clinically significant. A 2.76% incidence, where there is not gynecologist
      hospitalization, seems to be a high and relevant one. An alternative approach is
      to perform them only under certain clinical circumstances, although the process
      of collecting samples would make it a difficult task.

PMID- 7811773
TI  - [Pneumothorax in patients with AIDS].
AB  - METHODS: From January 1986 to 31 November 1993, 354 cases of AIDS (CDC criteria
      1987) were diagnosed. The possible existence of spontaneous pneumothorax at any
      time during the evolution and its presumed cause were evaluated. RESULTS: During
      the period studied, 7 (1.9%) of AIDS patients presented pneumothorax. The
      existence of a pulmonary infection was proven in 6: 3 pneumonia by Pneumocystis
      carinii, 2 bacterial pneumonia (Streptococcus pneumoniae and Pseudomonas sp.) and
      1 tuberculosis. One patient presented a Pneumocystis carinii pneumonia 3 months
      prior to the pneumothorax. In the study period 88 (22.8%) of the AIDS patients
      presented pneumonia by Pneumocystis carinii and 181 (51.1%) presented
      tuberculosis. The rate of pneumothorax in patients with a history or presence of
      pneumonia by Pneumocystis carinii was of 4.5% and 0.5% in patients with
      tuberculosis. CONCLUSIONS: The development of pneumothorax is relatively frequent
      in patients with AIDS in our area. As found in other series, its most frequent
      cause was Pneumocistis carinii pneumonia, despite the high incidence of
      tuberculosis.

PMID- 7811774
TI  - [The AIDS patient of the 90s (II)].

PMID- 7811775
TI  - [Skin nodules and epigastric pain in a patient with HIV infection].

PMID- 7811776
TI  - [Extravascular infections caused by Streptococcus adjacens. Report of 2 cases].

PMID- 7811777
TI  - [Prolonged fever and Mycoplasma pneumoniae infection].

PMID- 7811778
TI  - [Pericardial tamponade as initial manifestation of pulmonary tuberculosis].

PMID- 7811779
TI  - [Rhodococcus equi pneumonia in a patient with AIDS. Primary resistance to
      imipenem].

PMID- 7811780
TI  - [Eikenella corrodens pneumonia in a non-immunocompromised host].

PMID- 7811781
TI  - [Pneumocystis carinii pneumonia in an immunocompetent infant].

PMID- 7811782
TI  - [HIV-2 AIDS in Guipuzcoa].

PMID- 7811783
TI  - [Penicillin and erythromycin resistance in community-acquired pneumococcal
      pneumonia].

PMID- 7811784
TI  - The relationship between 24-hour ambulatory blood pressures and laboratory
      measures of cardiovascular reactivity.
AB  - The relationship between 24-hour ambulatory blood pressures (ABP) and blood
      pressures (BP) obtained during laboratory stressors was examined. Thirty
      normotensives (equal males and females) underwent ABP monitoring on three
      occasions separated by a week. They also underwent a laboratory assessment which
      included standard stressors (i.e., mental arithmetic, cold pressor, orthostatic
      response, treadmill exercise). Correlational analyses found laboratory pressures
      to be significantly correlated with ambulatory pressures, with laboratory
      baseline BPs showing higher correlations to the ambulatory BPs than the BPs
      obtained during laboratory stressors. In addition, gender effects were examined.
      In the correlational analyses between ABPs and laboratory BPs, males and females
      did not differ significantly in the strength of the correlations. In terms of
      absolute values, males were found to have significantly higher SBP during
      ambulatory monitoring, random-zero recordings, calibration readings, and during
      baselines of the laboratory assessment. There were no gender effects for these
      measures with respect to diastolic blood pressure or heart rate. There were also
      no gender effects on reactivity to laboratory stressors as measured by change
      scores. Exploratory analyses found no significant effect of history of familial
      hypertension on either the ABPs or the laboratory pressures.

PMID- 7811785
TI  - Slowed respiration training.
AB  - A method of slowed respiration rate (RR) training is described that uses visual
      feedback of the respiratory cycle. Subjects assigned to the slowed RR training
      procedure were compared with subjects assigned to either a traditional frontal
      electromyographic (EMG) biofeedback condition or a control condition where no
      feedback was presented. RR, frontal EMG, heart rate, digital temperature, and
      skin conductance level were monitored simultaneously. The results indicated that
      RR training was effective in reducing RR, that RR training had little systematic
      effect on the other physiological variables, and the frontal EMG procedure did
      not in itself reduce RR. The advantages of the current methodological approach
      and the importance of respiration training were discussed along with a literature
      review. The relationship between RR training and the complexities of respiratory
      phenomena was discussed, as well as ways that future research using this method
      may help clarify current issues within respiration training.

PMID- 7811786
TI  - Autogenic training: a narrative and quantitative review of clinical outcome.
AB  - This review of controlled outcome research on Autogenic Training complements the
      literature by pooling narrative and quantitative approaches, by including only
      studies with experimental controls, by integrating the English and German
      literature, and by adding research findings published since the last review.
      Whereas previous reviews have already reported positive effects of Autogenic
      Training for migraine, insomnia, and test anxiety, additional supportive findings
      for angina pectoris, asthma, childbirth, eczema, hypertension, infertility,
      Raynaud's disease, and recovery from myocardial infarction are discussed here.
      The impact of protocol variations on outcome is described, and the specificity of
      Autogenic Training relative to other stress management techniques is highlighted.
      Quantitative findings suggested that Autogenic Training was associated with
      medium-sized pre- to posttreatment effects ranging from d = .43 for biological
      indices of change to d = .58 for psychological and behavioral indices thus
      matching effect sizes for other biobehavioral treatment techniques like
      biofeedback and muscular relaxation. Length of treatment did not affect clinical
      outcome. The discussion emphasizes how narrative and quantitative strategies
      complement one another.

PMID- 7811787
TI  - Gamete spawning and fertilization in the gymnolaemate bryozoan Membranipora
      membranacea.
AB  - The simultaneously hermaphroditic zooids of Membranipora membranacea colonies
      spawn primary oocytes and spermatozeugmata (aggregates of 32 or 64 spermatozoa)
      into ambient seawater. Eggs are released through the intertentacular organ (ITO)
      whereas spermatozeugmata are spawned through the tips of the two distomedial
      tentacles. Fertilized eggs undergo planktotrophic development to form long-lived
      cyphonautes larvae. Examination of ovarian, coelomic, and spawned oocytes for
      sperm nuclei, using either Bisbenzimide H33342 or aceto-orcein staining, revealed
      that a single sperm fuses with primary oocytes during or shortly after ovulation.
      In M. membranacea, egg activation does not immediately follow sperm-egg fusion,
      but occurs after oocytes are spawned through the ITO. The period between sperm
      egg fusion and egg activation may last up to four days. Once zygotes begin to
      develop, they follow an Ascaris-type of fertilization pattern (Wilson, 1925).
      Internal sperm-egg fusion does not preclude cross-fertilization in M.
      membranacea, because spawned spermatozeugmata enter maternal coeloms through ITOs
      after being drawn into lophophores. The ITO actively regulates the entrance of
      spermatozeugmata and the release of oocytes by the closure of the distal pore.
      The ITO does not act as a filter to prevent self-fertilization, so that the
      paternal colony may also function as the maternal colony. Self-fertilization may
      be reduced in M. membranacea via increasing sperm dispersal away from the
      paternal colony, which is accomplished by the bending of the distomedial
      tentacles such that they release spermatozeugmata into the exhalent feeding
      current of the colony.

PMID- 7811789
TI  - Neurofilament-like immunoreactivity in the sea anemone Condylactis gigantea
      (Cnidaria: Anthozoa).
AB  - The neuronal cytoskeleton contains neurofilament proteins that serve as markers
      for nervous tissue in many species across phyla. Antiserum generated to mammalian
      neurofilaments was used for immunocytochemical staining of tissues in the sea
      anemone Condylactis gigantea (Cnidaria: Anthozoa). Specific staining, visible at
      the light and electron microscope levels, was found in the tissues of the
      tentacle. Proteins were extracted from the tissues and solubilized. SDS
      polyacrylamide gel electrophoresis and Western blotting revealed two bands of MWr
      156 kD and 74 kD that reacted with antiserum generated to neurofilaments. The
      protein bands also bound a monoclonal antibody shown to react with a highly
      conserved epitope in many classes of intermediate filaments. These data suggest
      that the neurons of this anthozoan contain neurofilament-like proteins with
      molecular properties similar to those of mammalian neurons.

PMID- 7811788
TI  - Characterization and solubilization of the FMRFamide receptor of squid.
AB  - The optic lobe of squid (Loligo pealei) contains FMRFamide receptors that can
      bind an iodinated FMRFamide analog: [125I]-desaminoTyr-Phe- norLeu-Arg-Phe-amide
      ([125I]-daYFnLRFa). Radioligand binding assays revealed that squid FMRFamide
      receptors are specific, saturable, high affinity sites (Kd = 0.15 nM) densely
      concentrated in optic lobe membranes (Bmax = 237 fmole/mg protein). The receptors
      appeared to be coupled to Gs because guanine nucleotides inhibit receptor binding
      and the stimulation of adenylate cyclase by FMRFamide is GTP-dependent. Both the
      binding and cyclase data showed that FMRFamide, but not FMRF-OH, interacts at
      FMRFamide receptors; thus the C-terminal Arg-Phe-amide is critical for binding.
      The high binding affinity of FMRFamide (0.4 nM IC50) was specific for FMRFamide
      like peptides. The structure-activity relations of many FMRFamide analogs were
      defined in detail and were nearly identical for both the membrane-bound and
      detergent-solubilized receptors. We also found that squid optic lobe contains
      FMRFamide-like reactivity as measured with both a radioimmunoassay and a
      radioreceptor assay. Moreover, we have sequenced a fragment of genomic DNA that
      encodes a FMRFamide precursor. Our findings in sum suggest that FMRFamide is a
      neurotransmitter in squid optic lobe, and that this tissue is a good source from
      which to purify FMRFamide receptors.

PMID- 7811790
TI  - Preliminary investigation of the molecular basis for the functional differences
      between the two pentraxins limulin and C-reactive protein from the plasma of the
      American horseshoe crab, Limulus polyphemus.

PMID- 7811791
TI  - High resolution multimode digital imaging system for mitosis studies in vivo and
      in vitro.

PMID- 7811792
TI  - Through-focal and time-lapse stereoscopic imaging of dividing cells and
      developing embryos in DIC and polarization microscopy.

PMID- 7811793
TI  - Study of calcium signaling in cell cleavage using confocal microscopy.

PMID- 7811794
TI  - Video light microscopic imaging of the calcium signal that initiates nuclear
      envelope breakdown in sand dollar (Echinaracnius parma) cells.

PMID- 7811795
TI  - Analysis of spatial and temporal patterns in the Ca2+ signal that signals nuclear
      envelope breakdown in sand dollar (Echinaracnius parma) cells.

PMID- 7811796
TI  - Inhibitory cell-cell interactions control development in the embryos of
      Cerebratulus lacteus.

PMID- 7811797
TI  - Oscillations in free [Ca2+]i during early cell division cycles in Xenopus laevis
      embryos.

PMID- 7811798
TI  - Mitosis, cleavage, and development of highly compressed sea urchin (Lytechinus
      variegatus) zygotes.

PMID- 7811799
TI  - Leukotriene B4, an arachidonic acid metabolite, regulates intracellular free
      calcium release in eggs and mitotic cells of the sand dollar (Echinaracnius
      parma).

PMID- 7811800
TI  - Muscle fine structure and microtubule birefringence measured with a new pol
      scope.

PMID- 7811801
TI  - Copper induced polymerization of hemoglobin from the ocean pout, Macrozoarces
      americanus.

PMID- 7811802
TI  - Catalase activity in dogfish (Mustelus canis) ocular tissues.

PMID- 7811803
TI  - NG-monomethyl-L-arginine inhibits Arbacia fertilization and differentiation.

PMID- 7811804
TI  - Enzymatic hydrolysis of tetriso as a model for the detoxication of the neurotoxic
      agent VX.

PMID- 7811805
TI  - Lead toxicity in Hermissenda crassicornis embryos and cultured neurons.

PMID- 7811806
TI  - Hermissenda crassicornis larvae metamorphose in laboratory in response to
      artificial and natural inducers.

PMID- 7811807
TI  - Experimental disinfection of lobster eggs infected with Leucothrix mucor.

PMID- 7811808
TI  - Microsporidian spore invasion tubes as revealed by fluorescent probes.

PMID- 7811809
TI  - Neural network with embedded oscillators.

PMID- 7811810
TI  - Operational properties of voltage-clamped electroreceptive ampullary organ
      excised from Raja.

PMID- 7811811
TI  - Directional sensitivity of saccular afferents of the toadfish to linear
      acceleration at audio frequencies.

PMID- 7811812
TI  - Time course of recovery from adaptation by hydroxyproline-sensitive lobster
      olfactory receptor neurons.

PMID- 7811813
TI  - Visual responses in the brain of Limulus.

PMID- 7811814
TI  - Noise components in Limulus vision.

PMID- 7811815
TI  - The effects of quinine and quinidine on isolated retinal horizontal cells.

PMID- 7811816
TI  - The GABAA receptors of Muller (glial) cells in skate retina.

PMID- 7811817
TI  - Effects of GABA on outward currents in Hermissenda photoreceptors.

PMID- 7811818
TI  - Calcium and voltage sensitivity of potassium current activation in toadfish
      semicircular canal hair cells.

PMID- 7811819
TI  - Protein synthesis in nerve endings from squid brain: modulation by calcium ions.

PMID- 7811820
TI  - Second messenger modulation of steady-state calcium efflux in Aplysia bag cells.

PMID- 7811821
TI  - Lobster orientation in turbulent odor plumes: simultaneous measurement of
      tracking behavior and temporal odor patterns.

PMID- 7811822
TI  - Lobster Orientation in turbulent odor plumes: electrical recording of bilateral
      olfactory sampling (antennular "flicking").

PMID- 7811823
TI  - Food detection and preferences of the nudibranch mollusc Hermissenda
      crassicornis: experiments in a Y-maze.

PMID- 7811824
TI  - Aggression-reducing courtship signals in the lobster, Homarus americanus.

PMID- 7811826
TI  - The lactulose hydrogen breath test as a measure of orocaecal transit time.
AB  - OBJECTIVE: To establish normal values and assess the reproducibility of the
      lactulose hydrogen breath test in measuring orocaecal transit time in control
      subjects, and to report results in a group of patients with chronic constipation
      as a result of colonic inertia. DESIGN: Open study. SETTING: Academic clinic.
      SUBJECTS: 42 Control subjects (29 women and 13 men) in 25 of whom the test was
      repeated within 2-4 weeks, and 19 patients. INTERVENTIONS: Lactulose hydrogen
      breath test. MAIN OUTCOME MEASURES: Sustained increase in hydrogen production of
      3 ppm or more. RESULTS: Coefficient of variation within subjects was 8% compared
      with 38% between subjects; 3 of the control subjects (7%) and 3 of the patients
      (16%) did not ferment lactulose, the the incidence was similar in men (1/13, 8%)
      and women (2/29, 7%). Mean (SD) orocaecal transit time was significantly shorter
      among the 29 women (60 (27) minutes) than among the 11 men (89 (24) minutes) (p <
      0.005). There were no significant differences between men in the control group
      and those with constipation. CONCLUSIONS: The lactulose hydrogen breath test is
      valuable to assess orocaecal transit time. It is simple, non-invasive, and
      reproducible, and may be of value in differentiating between generalised
      hypomotility and colonic inertia.

PMID- 7811825
TI  - Haemorrhage-induced increases in glucose, glucagon and insulin levels are blocked
      by naloxone in rats.
AB  - OBJECTIVE: To find out if the opioids that are liberated during bleeding
      influence the concentrations of glucagon, insulin, somatostatin, corticosterone
      and glucose in rats, and if naloxone has any regulatory effect. DESIGN:
      Laboratory study. SETTING: University hospital. MATERIAL: 56 Male Wistar rats.
      INTERVENTIONS: Removal of blood corresponding to 2% of body weight through a
      catheter in the internal jugular vein. Before bleeding (n = 8), and at 5, 15 and
      30 minutes afterwards (n = 16 at each time point, half of which had received
      naloxone 0.04 mg/ml, 0.7 ml/hour, for 10 minutes before bleeding and up to 30
      minutes afterwards) rats were killed and samples of heart blood taken. MAIN
      OUTCOME MEASURES: Concentrations of glucose, glucagon, insulin, somatostatin, and
      corticosterone in heart blood. RESULTS: In the control group (saline)
      concentrations of glucose, glucagon and insulin increased significantly after
      bleeding, and had returned to baseline concentration by 30 minutes. Naloxone
      blocked the increases in the treated group. CONCLUSION: Endogenous opioids,
      possibly endorphin, may be important in the acute regulation of blood glucose,
      glucagon and insulin concentrations after haemorrhage.

PMID- 7811827
TI  - Clinical meaning of DNA content in the long term behaviour of follicular thyroid
      tumours: a 12-year follow up.
AB  - OBJECTIVE: To find out if there was any correlation between the DNA aneuploidy in
      benign tumours and in malignant follicular tumours of the thyroid and the
      progression of either disease. DESIGN: Retrospective study. SETTING: University
      hospital. SUBJECTS: 71 of 75 patients who had had cytofluorimetric nuclear DNA
      analyses done on their follicular thyroid tumours during the period 1977-1980,
      and for whom clinical follow up data were available. MAIN OUTCOME MEASURES:
      Correlation between clinical course and finding of aneuploidy in original
      histological specimens. RESULTS: Aneuploidy was found in 6/40 follicular
      adenomas, 3/17 adenomatous goitres, and in 13/14 follicular carcinomas. The
      patients were examined after 12 years, when there had been no recurrences of the
      benign tumours. 5 of the patients with carcinoma had died of distant metastases,
      all of whom had aneuploid stemlines. There are, however, 8 patients with
      carcinomas and aneuploidy who are still alive with no recurrences or metastases.
      CONCLUSIONS: DNA aneuploidy indicates neither the invasiveness nor the metastatic
      potential of follicular thyroid tumours, and does not distinguish between the
      minimally invasive (encapsulated) and highly invasive carcinomas.

PMID- 7811828
TI  - Ability to work after arterial surgery for chronic incapacitating ischaemia of
      the lower limb in middle-aged patients.
AB  - OBJECTIVE: To assess the efficacy of arterial surgery in restoring ability to
      walk and working capacity. DESIGN: Retrospective follow up study. SETTING: Fourth
      Department of Surgery, Helsinki University Central Hospital. SUBJECTS: 67 middle
      aged patients (mean age 53 years) with chronic incapacitating ischaemia of the
      lower limb. INTERVENTIONS: Arterial reconstruction. MAIN OUTCOME MEASURES:
      Clinical outcome, vascular laboratory assessments, mortality, morbidity, return
      to work, and retirement. RESULTS: According to objective vascular laboratory
      criteria a primary positive effect was achieved in 63/67 (94%). Fourty-eight of
      the 65 surviving patients (74%) were free of symptoms on treadmill testing three
      months after the operation. Working capacity was restored in 41/50 of the
      patients not yet retired (82%). Three years postoperatively 77% of the surviving
      patients still fared objectively better than before operation. The 10-year
      survival rate was 67%. Fourteen of the 22 patients who died did so of
      cardiovascular diseases (64%). Advanced distal ischaemia (indicated by a
      preoperative ankle-brachial index of 0.5 or less) was associated with increased
      risk of death. Altogether 251 working years were achieved of the 435 that could
      have potentially been gained. The most common reason for retirement during follow
      up was progression of peripheral arterial disease in the lower limbs in 13/41
      patients (32%). At the end of the study there were nine patients still working
      with potentially 73 working years left. CONCLUSION: These results indicate that
      arterial surgery can restore working capacity in middle aged patients with
      threatening or temporary invalidity. Long term outcome, especially mortality, is
      mostly affected by other signs of cardiovascular disease, whereas working
      capacity is dependent on a wider variety of factors.

PMID- 7811830
TI  - Macrophage phagocytic dysfunction and reduced metabolic response in experimental
      obstructive jaundice.
AB  - OBJECTIVE: To investigate the metabolic response as measured by microcalorimetry
      and the phagocytic activity or peritoneal macrophages that had been harvested
      from jaundiced and normal rats and incubated with Escherichia coli in vitro.
      DESIGN: Open laboratory study. SETTING: University departments of surgery and
      immunology. MATERIAL: 12 Male Sprague-Dawley rats. INTERVENTIONS: Ligation and
      transsection of the common bile duct (n = 6) or sham operation (n = 6). MAIN
      OUTCOME MEASURES: Metabolic response (pW/cell) measured by microcalorimetry and
      phagocytic function assessed by light microscopy after Giemsa stain two weeks
      after operation. RESULTS: The mean (SEM) maximal metabolic response of
      macrophages and the metabolic rate one hour after inoculation with E coli were
      significantly reduced in jaundiced rats compared with controls (6.95 (1.95)
      compared with 27.39 (7.24), p = 0.005, and 5.50 (1.05) compared with 20.10 (3.35)
      p = 0.016, respectively) as were the number of E coli phagocytosed by macrophages
      harvested from jaundiced animals (p = 0.0002). CONCLUSION: The reduced metabolic
      response and phagocytosis of E coli by peritoneal macrophages in rats by biliary
      obstruction is a sign of depressed reticuloendothelial function. This mechanism
      may explain the high incidence of infective complications inpatients with
      obstructive jaundice.

PMID- 7811829
TI  - Intraoperative flow measurement of distal runoff: a valid predictor of outcome of
      infrainguinal bypass surgery.
AB  - OBJECTIVE: To assess the power of operative flow measurements in the prediction
      of outcome after infrainguinal bypass operations for critical ischaemia DESIGN:
      Open study SETTING: University department of vascular surgery SUBJECTS: 197
      patients operated on for critical ischaemia between 1 January 1982 and 31
      December 1989 under the care of one surgeon. INTERVENTIONS: Standard operative
      angiography and measurement of flow of distal runoff MAIN OUTCOME MEASURES:
      Patency and limb salvage RESULTS: All patients were followed up prospectively
      until 31 March 1991 or death. The estimated 5 year rates of primary patency and
      limb salvage were 0.75 and 0.86, respectively. Multivariate analysis showed that
      flow measurement was the most powerful predictor of graft patency (p = 0.0003)
      and limb salvage (p = 0.004) of all factors studied, including angiography.
      Irrespective of the site of distal anastomosis no polytetrafluoroethylene (PTFE)
      graft remained patent if the flow was less than 50 m/minute, whereas vein grafts
      remained patent if the flow was as little as 10 ml/minute. CONCLUSIONS: Flow is
      easy to measure and is a better predictor of outcome than angiography. Decisions
      about grafting should rely on flow measurements if there is any doubt about
      patency or limb salvage, particularly if a PTFE graft is going to be used.

PMID- 7811831
TI  - Evaluation of 18 cases of conservative proctectomy with low transsection of the
      anorectum for benign diseases.
AB  - OBJECTIVE: To present our experience of conservative proctectomy in the treatment
      of patients with benign diseases of the rectum. DESIGN: Retrospective study.
      SETTING: University hospital. SUBJECTS: 18 patients with benign diseases of the
      rectum for whom a pouch was unsuitable. INTERVENTIONS: Conservative proctectomy
      with transsection of the anorectum. MAIN OUTCOME MEASURES: Mortality and
      morbidity. RESULTS: In 10 patients the wounds healed primarily. The remaining 8
      developed presacral abscesses, which drained either spontaneously or after a
      drainage operation. At the end of the 19 month follow up period four still had
      presacral cavities with fistulas to the anal canal, and one patient had died of a
      cause unrelated to the operation. No patient complained of sexual dysfunction.
      CONCLUSION: If proctectomy is indicated for a benign disease a limited excision
      with transsection of the anorectum at the pectinate line is safe if the closed
      anal canal is examined carefully and residual mucosa removed. It should not be
      used for patients with severe inflammatory or fibrous changes in the perirectal
      tissue.

PMID- 7811832
TI  - An unusual complication of hydatid disease of the liver: spontaneous operative
      rupture of the inferior vena cava into the cyst wall. Case report.

PMID- 7811833
TI  - Tuberculous peripancreatic abscess. Case report.

PMID- 7811834
TI  - Jejunojejunal intussusception after Roux-en-Y gastrojejunostomy: a rare cause of
      postoperative bowel obstruction in an adult. Case report.

PMID- 7811835
TI  - Recurrent fatal spontaneous perforation of the large bowel of unknown origin in a
      young woman. Case report.

PMID- 7811836
TI  - Jejunoportal fistula. Case report.

PMID- 7811837
TI  - Cysts of the tailgut. Two cases.

PMID- 7811838
TI  - Catatonia in DSM-IV.

PMID- 7811839
TI  - A linkage study of affective disorder with DNA markers for the ABO-AK1-ORM
      linkage group near the dopamine beta hydroxylase gene.
AB  - Combining data from a number of studies has provided evidence for a
      susceptibility allele for affective disorder near to the ABO-AK1-ORM region on
      chromosome 9q34. The dopamine beta hydroxylase gene locus is also at 9q34. Five
      multigenerational families with bipolar and unipolar affective disorder were
      analyzed for linkage with highly polymorphic microsatellite markers from the
      candidate region. The segregation of the illness in these families was compatible
      with an autosomal dominant susceptibility allele. Linkage analyses using
      conservative parameters seemed to provide strong evidence against a major
      susceptibility allele in this region including the candidate gene dopamine beta
      hydroxylase in these families.

PMID- 7811840
TI  - Assessment of recovery of electrophysiological and neuropsychological functions
      in chronic alcoholics.
AB  - Potential recovery of electrophysiological and neuropsychological functions was
      investigated in alcoholics completing treatment and controls. Event-related
      potentials (ERPs) and neuropsychological tests were administered initially and
      repeated 14 months later. Alcoholics were classified as resumers or abstainers
      based on consumption patterns before retest. Resumers (n = 28), abstainers (n =
      44), and controls (n = 44) differed significantly on ERP measures. No test-retest
      or group x test-retest interactions were found, indicating little recovery or
      change in ERPs over time. Differences between groups could not be attributed to
      family history factors. For neuropsychological efficiency (Accuracy/Time)
      measures, significant group differences were found. All groups improved from test
      to retest, with resumers showing the greatest improvement. Analysis of the
      separate efficiency components indicated resumers' improvement was due to a
      decrease in performance time, whereas accuracy scores remained significantly
      impaired. Whether the continued deficits in ERPs and neuropsychological
      performance at retest is a permanent effect of alcohol abuse, or would remit over
      longer periods of time, or reflects premorbid deficits, remains to be
      investigated.

PMID- 7811841
TI  - Lateralization of the Bereitschaftspotential to the left hemisphere in patients
      with major depression.
AB  - Fourteen patients with major depression and 18 healthy subjects performed a
      Bereitschaftspotential (BP) paradigm, which required them to clench the right
      fist at self-paced intervals. The BP was calculated as the integrated negative
      amplitude from BP onset to movement onset. The latter was defined by recording
      the electromyogram (EMG) from the right forearm. To evaluate lateralization, the
      integrated BPs at C3, C4, P3, and P4 were analyzed. In depressives, a significant
      asymmetry of the BP to the left was found, whereas in normals the BP was nearly
      symmetrically distributed around the midline. Three patients were retested when
      clinically improved. At that time the asymmetry to the left hemisphere had nearly
      vanished. This asymmetry to the left hemisphere is interpreted as a cortical
      deactivation of the right cerebral hemisphere and seems to be a state marker of
      depression.

PMID- 7811842
TI  - Platelet [3H]paroxetine binding, 5-HT-stimulated Ca2+ response, and 5-HT content
      in winter seasonal affective disorder.
AB  - The present study was designed to evaluate cellular serotonergic functions in
      winter seasonal affective disorder (SAD) using serotonin (5-HT)-stimulated Ca2+
      response as an integrated measure of 5-HT2 receptor function in platelets,
      [3H]paroxetine binding to characterize the platelet 5-HT transporter and 5-HT
      content as an index of the platelet storage capacity for this neurotransmitter
      amine. Purified density-dependent subpopulations of platelets in untreated and
      light-treated SAD patients and matched controls were investigated in order to
      control for possible variations in platelet turnover. We found no differences
      between SAD patients and controls on any of the measures, nor between light
      therapy conditions in SAD patients, although we found a higher Bmax of
      [3H]paroxetine binding and 5-HT content in heavy platelets compared to light
      platelets. Although the validity of platelet serotonergic measures as a model for
      brain serotonergic systems still remains to be elucidated, we found no evidence
      of platelet serotonergic abnormalities in our sample of SAD patients.

PMID- 7811843
TI  - Pharmacogenetic response to antidepressants in a multicase family with affective
      disorder.
AB  - Eight members from two generations of a family met the DSM-III-R criteria for
      major depression. Four individuals had severe prolonged depressive disorders that
      did not respond to standard therapeutic doses of tricyclic and new generation
      antidepressants, but subsequently responded to the monoamine oxidase inhibitor,
      tranylcypromine. The literature on pharmacogenetics of the antidepressants is
      sparse. The pattern of selective response to tranylcypromine in this family
      supports the view that there is a familial tendency to respond to specific
      antidepressants or antidepressant groups. A history of response to a specific
      antidepressant in a relative may be helpful when selecting an antidepressant.
      Families demonstrating preferential response to specific psychotropics may be
      suitable pedigrees in which to perform linkage analysis using candidate genes
      related to the site of action of that psychotropic drug.

PMID- 7811844
TI  - Total cholesterol and suicidality in depression.
AB  - There exists considerable controversy regarding an association between low total
      cholesterol and increased mortality from suicide. As suicide mortality is a crude
      marker for suicidal ideation and behavior, we investigated the association
      between total cholesterol and suicidality in a depressed sample. Ninety men and
      women meeting structured criteria for a major depressive episode of at least
      moderate severity participated in a study of predictors of treatment response. A
      three level variable codified the degree of suicidality in the previous month: no
      suicidal thoughts (39/90), suicidal ideation or plan (38/90), and a suicide
      attempt (13/90). There was a significant univariate association between lower
      cholesterol levels and increasing degrees of suicidality. In a multivariate
      analysis, this association was the only one that neared statistical significance
      (p = 0.068). Although it is premature to conclude that these variables are
      causally associated, data from a number of sources suggest that this association
      is worthy of further study.

PMID- 7811845
TI  - BR-16A protects against ECS-induced anterograde amnesia.
AB  - BR-16A is an herbal (non allopathic) medication used in India to enhance
      cognition. In experiment 1, 28 Wistar rats received either BR-16A (200 mg/kg/day)
      or vehicle alone for 3 weeks. During the third week, the rats were tested for
      learning in the Hebb Williams complex maze. BR-16A-treated rats showed
      significantly better learning than did controls. Experiment 2 was conducted
      identically except that during the second week all of 32 rats additionally
      received six once-daily electroconvulsive shocks (ECS). An advantage for learning
      was again demonstrated for the BR-16A group. It is concluded that BR-16A
      facilitates learning, and that this effect extends to a protection against ECS
      induced anterograde amnesia. Cognitive deficits induced by electroconvulsive
      therapy are a major disadvantage of the treatment and, to-date, no drug has been
      found to offer satisfactory protection against such deficits. It is suggested
      that BR-16A may hold promise in the containment of electroconvulsive therapy
      (ECT)-induced cognitive compromise.

PMID- 7811846
TI  - CSF antibodies for dynorphin bind synthetic Staphylococcus aureus replication
      protein B 275-290.

PMID- 7811847
TI  - Moderate hyponatremia and death in a polydipsic schizophrenic on lithium.

PMID- 7811848
TI  - Potential impact of valproic acid therapy on clozapine disposition.

PMID- 7811850
TI  - Further evidence for a specific role of estradiol in schizophrenia?

PMID- 7811849
TI  - Depletion of glutathione and enhanced lipid peroxidation in the CSF of acute
      psychotics following haloperidol administration.

PMID- 7811851
TI  - Platelet GTP-binding protein in long-term abstinent alcoholics with an alcoholic
      first-degree relative.

PMID- 7811852
TI  - Lithium involvement in physostigmine-induced seizures.

PMID- 7811853
TI  - Cytokines in major depression.

PMID- 7811854
TI  - Hantaviruses and hantavirus pulmonary syndrome.

PMID- 7811855
TI  - Conventional diagnostic methods for tuberculosis.

PMID- 7811857
TI  - Photo quiz. Chronic (adult-type) disseminated histoplasmosis.

PMID- 7811856
TI  - Brain abscess following marrow transplantation: experience at the Fred Hutchinson
      Cancer Research Center, 1984-1992.
AB  - The etiology of brain abscess in patients undergoing marrow transplantation at
      the Fred Hutchinson Cancer Research Center in Seattle was assessed in a
      retrospective review. Fifty-eight patients with histology- or culture-proven
      brain abscess diagnosed between January 1984 and March 1992 were identified. A
      fungus was isolated in 92% of cases. Aspergillus species were the most prevalent
      fungi (58% of cases), and Candida species were second in frequency (33%);
      sporadic cases were caused by Rhizopus, Absidia, Scopulariopsis, and
      Pseudallescheria species. Bacteria were involved in fewer than 10% of cases.
      There was no appreciable variation from year to year in the incidence of brain
      abscess over this period. Aspergillus brain abscess was associated with
      concomitant pulmonary disease (87% of cases), whereas candida brain abscess often
      occurred in association with fungemia (63% of cases) or neutropenia (63%).
      Mortality was high (97%); the risk of death was unrelated to etiology or
      therapeutic regimen. Since the etiology of brain abscess in patients undergoing
      marrow transplantation is primarily fungal, the development of better antifungal
      therapeutic and/or prophylactic modalities is warranted.

PMID- 7811858
TI  - Routine analysis of induced sputum is not an effective strategy for screening
      persons infected with human immunodeficiency virus for Mycobacterium tuberculosis
      or Pneumocystis carinii. Pulmonary Complications of HIV Infection Study Group.
AB  - A prospective multicenter cohort study comprising 1,171 individuals who were
      seropositive for human immunodeficiency virus (HIV) but did not have AIDS at the
      time of enrollment and 182 HIV-seronegative controls, was studied by means of
      routine induced-sputum analysis in an attempt to detect occult tuberculosis or
      Pneumocystis carinii pneumonia. One occult case of tuberculosis was discovered
      upon the patient's enrollment (at baseline); none were discovered during follow
      up. Two additional Mycobacterium tuberculosis isolates were recovered (one at
      baseline, one during follow-up) from subjects with symptoms or abnormalities
      evident on chest roentgenograms. Three specimens were false-positive (one for M.
      tuberculosis, two for P. carinii). Five pathogenic nontuberculous mycobacteria
      isolates were recovered during follow-up. Nonpathogenic, nontuberculous
      mycobacteria were recovered from 51 (4.6%) of 1,113 baseline specimens and 56
      (3.7%) of 1,518 follow-up specimens, primarily at a center where the water supply
      was contaminated. We conclude that routine induced-sputum analysis is not an
      effective strategy for screening HIV-infected asymptomatic subjects for
      tuberculosis or P. carinii pneumonia before the onset of clinically recognizable
      disease activity.

PMID- 7811859
TI  - Serious Pseudomonas aeruginosa infections in patients infected with human
      immunodeficiency virus: a case-control study.
AB  - We conducted a case-control study to determine the incidence and clinical
      features of and risk factors for Pseudomonas aeruginosa infections in patients
      infected with human immunodeficiency virus (HIV). Twenty-five patients who had 37
      episodes of P. aeruginosa infection from 1990 through 1992 were identified. Most
      of the patients (92%) were homosexual men with low CD4+ lymphocyte counts and a
      history of AIDS. The annual incidence rates of P. aeruginosa infection were 3.5%
      (1990), 6.3% (1991), and 8.7% (1992). Most infections were community-acquired
      (68%) and involved the respiratory tract (73%). Patients were more likely than
      HIV-infected controls to have AIDS and had more AIDS-defining opportunistic
      illnesses. The overall mortality was 36%. Recurrent episodes were common (39%).
      We conclude that P. aeruginosa infections may be an increasing problem in
      patients with extremely advanced HIV infection. Clinicians should consider
      including antibiotics with activity against P. aeruginosa in the empirical
      treatment for suspected bacterial infection in patients with advanced HIV
      infection.

PMID- 7811860
TI  - Invasive zygomycosis due to Conidiobolus incongruus.
AB  - During the past decade, an increasing spectrum of pathogenic Zygomycetes fungi
      have caused infections in humans. The preponderance of these deeply invasive
      infections have been caused by members of the order Mucorales. However, deeply
      invasive zygomycoses due to genera of the order Entomophthorales (Conidiobolus
      species and Basidiobolus species) have seldom been reported. We describe a
      granulocytopenic patient with pulmonary and pericardial zygomycosis due to
      Conidiobolus incongruus, describe this organism's susceptibility to antifungal
      agents, characterize its diagnostic microbiological characteristics, and review
      previously reported cases of deeply invasive zygomycosis due to Conidiobolus
      species. In immunocompromised patients, C. incongruus is an uncommon but highly
      invasive fungal pathogen that may be resistant to amphotericin B and can be
      distinguished from other Zygomycetes fungi by characteristic mycological
      features.

PMID- 7811861
TI  - Trimethoprim-induced aseptic meningitis in a patient with AIDS: case report and
      review.
AB  - We report the case of a 41-year-old man infected with human immunodeficiency
      virus who had two episodes of aseptic meningitis that occurred 2 weeks apart; the
      first was associated with ingestion of trimethoprim-sulfamethoxazole (TMP-SMZ)
      and the second was associated with ingestion of TMP alone. Onset of fever,
      headache, and flushing was abrupt, followed by somnolence, hearing loss, and
      aphasia. Analysis of the CSF showed pleocytosis and an elevated protein level.
      The findings resolved within 48 hours after withdrawal of the drug. We also
      review 18 previously reported cases of TMP-SMZ- or TMP-induced meningitis, 17 of
      which occurred in women. In all of these cases, a similar abrupt onset and
      resolution were noted. Six of the 18 patients had collagen-vascular diseases. All
      but two of these patients had multiple recurrent episodes of meningitis before
      the diagnosis was made. We conclude that the diagnosis of TMP-SMZ- or TMP-induced
      meningitis should be considered when a patient receiving these drugs has
      recurrent episodes of aseptic meningitis.

PMID- 7811862
TI  - Anaerobic pericarditis: case report and review.
AB  - Purulent pericarditis is uncommon and is rarely caused by anaerobic bacteria. We
      describe a 58-year-old man with purulent pericarditis secondary to infection with
      Bacteroides fragilis; the most likely source for the B. fragilis infection was
      subsequently found to be a ruptured appendix. His pericarditis eventually
      resolved after drainage of purulent fluid and treatment with antibiotics directed
      against B. fragilis. We also review 29 cases of anaerobic pericarditis previously
      reported in the English-language literature (we excluded those cases due to
      actinomyces). In 17 cases only anaerobic bacteria were isolated, while in 13
      anaerobes were isolated with a mixture of facultative and/or aerobic bacteria.
      The cases were secondary to a contiguous focus of infection or occurred via
      hematogenous seeding. Treatment of both anaerobic pericarditis and purulent
      pericarditis due to aerobic bacteria entails adequate drainage and appropriate
      antibiotic therapy, and in all cases there should be a search for the source of
      the organism infecting the pericardium.

PMID- 7811863
TI  - Sexual behavior and perceived risk of AIDS among men in Kenya attending a clinic
      for sexually transmitted diseases.
AB  - The sexual transmission of human immunodeficiency virus type 1 (HIV-1) continues
      at an alarming rate in sub-Saharan Africa despite the fact that awareness of AIDS
      is high. One explanation for this alarming rate may be that individuals do not
      believe that they are personally at risk for AIDS and are not sufficiently
      motivated to make changes in their behavior. We conducted a cross-sectional study
      of men with genital ulcer disease to assess their sexual behavior and their
      perceived risk of AIDS. We studied 787 men between the ages of 17 and 54 years
      who presented to a referral clinic for sexually transmitted diseases (STDs) in
      Nairobi, Kenya. Of these 787 men, 188 (24%) were infected with HIV-1. Awareness
      of AIDS was essentially universal in this population; however, only 64 men (8%)
      thought that they were personally at risk of developing AIDS. A logistic
      regression analysis found that men who believed they were personally at risk knew
      someone with AIDS (odds ratio [OR], 8.9; 95% confidence interval [CI], 4.0-19.7),
      received information about AIDS from television or video (OR, 3.0; 95% CI, 1.7
      5.5), or had previously had an STD (OR, 2.2; 95% CI, 1.2-4.1). Except for a
      modest increase in condom use, there was no significant difference in sexual
      behavior between the group who considered themselves to be at risk for AIDS and
      the group who did not consider themselves to be at risk. The results of this
      study challenge the current strategies on HIV/AIDS education and prevention for
      urban men in Kenya.

PMID- 7811864
TI  - Simultaneous measurement of antibodies to Epstein-Barr virus, human herpesvirus
      6, herpes simplex virus types 1 and 2, and 14 enteroviruses in chronic fatigue
      syndrome: is there evidence of activation of a nonspecific polyclonal immune
      response?
AB  - As a test of the hypothesis that elevated titers of viral antibodies in patients
      with chronic fatigue syndrome (CFS) are due to a nonspecific polyclonal immune
      response, antibodies to Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6),
      and 14 enteroviruses in 20 patients with CFS and 20 age- and gender-matched
      controls were simultaneously measured. Similarly, titers of IgG to herpes simplex
      virus (HSV) types 1 and 2 were measured in 18 of these cases and in the
      respective controls. IgG to EBV viral capsid antigen (VCA) was present at titers
      > or = 1:320 in 55% of cases vs. 15% of controls (P = .02). The geometric mean
      titers of early antigen antibody to EBV, HHV-6 IgG, and HSV-1 and HSV-2 IgG were
      not significantly different among cases and controls. Of the 14 enteroviral
      antibodies tested for, only those to coxsackieviruses B1 and B4 were present at
      significant titers (> or = 1:8) in cases vs. controls (P = .02 and P = .001,
      respectively). Of the cases, 19 (95%) had either an EBV VCA IgG titer > or =
      1:320 or a coxsackievirus B1 or B4 antibody titer > or = 1:8, a percentage
      significantly higher than that of controls (40%; P = .0004). Titers of EBV VCA
      IgG and coxsackievirus B1 and B4 antibodies were simultaneously elevated in only
      20% of cases. There was no correlation between elevated titers of EBV VCA IgG and
      IgG to HHV-6, HSV-1, and HSV-2 or antibody to coxsackieviruses B1 and B4 in the
      cases. The prevalence of reported allergies to medications or other substances
      was identical in both groups (60%). These findings suggest that in the majority
      of cases of CFS, elevation of viral antibody titers is not due to a nonspecific
      polyclonal immune response.

PMID- 7811865
TI  - Severe measles pneumonitis in adults: evaluation of clinical characteristics and
      therapy with intravenous ribavirin.
AB  - Between February and April 1991, six adults were admitted to the New York
      Hospital because of measles pneumonitis. The diagnosis was confirmed by serology
      and/or viral culture. Uncommon clinical features among patients with this
      diagnosis included thrombocytopenia, hepatitis, myositis, and hypocalcemia. All
      patients were markedly hypoxic (initial alveolar--arterial oxygen gradients while
      the patients were breathing room air, 40-61 mm Hg); four required support with
      mechanical ventilation. All patients received therapy with intravenous ribavirin
      (20-35 mg/[kg.d]) for 1 week. The respiratory status of five patients (one of
      whom was positive for human immunodeficiency virus [HIV]) who were treated early
      (days 2-5 of illness) promptly improved; all abnormal parameters eventually
      returned to baseline. Treatment of the sixth patient, who was presumed to be HIV
      infected, was initiated on hospital day 22; this patient died of progressive
      oxygenation failure on day 38. We conclude that life-threatening measles
      pneumonitis in adults may be more common that previously appreciated, regardless
      of the patient's immune status. Therapy with intravenous ribavirin was well
      tolerated by our patients and was associated with reversal of respiratory
      compromise.

PMID- 7811866
TI  - Mechanisms of brain injury in bacterial meningitis: workshop summary.
AB  - Morbidity and mortality associated with bacterial meningitis remain high,
      although antibiotic therapy has improved during recent decades. The major
      intracranial complications of bacterial meningitis are cerebrovascular arterial
      and venous involvement, brain edema, and hydrocephalus with a subsequent increase
      of intracranial pressure. Experiments in animal models and cell culture systems
      have focused on the pathogenesis and pathophysiology of bacterial meningitis in
      an attempt to identify the bacterial and/or host factors responsible for brain
      injury during the course of infection. An international workshop entitled
      "Bacterial Meningitis: Mechanisms of Brain Injury" was organized by the
      Department of Neurology at the University of Munich and was held in Eibsee,
      Germany, in June 1993. This conference provided a forum for the exchange of
      current information on bacterial meningitis, including data on the clinical
      spectrum of complications, the associated morphological alterations, the role of
      soluble inflammatory mediators (in particular cytokines) and of leukocyte
      endothelial cell interactions in tissue injury, and the molecular mechanisms of
      neuronal injury, with potential mediators such as reactive oxygen species,
      reactive nitrogen species, and excitatory amino acids. It is hoped that a better
      understanding of the pathophysiological events that take place during bacterial
      meningitis will lead to the development of new therapeutic regimens.

PMID- 7811867
TI  - Immunologic and biochemical alterations in severe falciparum malaria: relation to
      neurological symptoms and outcome.
AB  - The relation between the immune response and the clinical features of severe
      falciparum malaria was studied in Burundian adults with (n = 31) and without (n =
      17) cerebral involvement. At the time of admission, mean values for age,
      temperature, and blood levels of hemoglobin, creatinine, bilirubin, and glucose
      were similar in the two groups. Plasma levels of tumor necrosis factor alpha,
      interferon gamma, interleukin 10 (IL-10), and soluble intercellular adhesion
      molecule 1 were similarly elevated in the two groups. Mean parasite counts and
      mean plasma levels of soluble E-selectin were higher in severe noncerebral
      malaria than in cerebral malaria and were correlated with each other. After
      adjustment for parasitemia, levels of soluble E-selectin remained higher in
      noncerebral malaria. All seven patients who died had cerebral disease. These
      patients had higher levels of creatinine, bilirubin, IL-10, and soluble E
      selectin than did patients with nonfatal cerebral malaria. After adjustment for
      creatinine and bilirubin levels, IL-10 and soluble E-selectin concentrations were
      similar in fatal and nonfatal cases of cerebral infection. In these African
      adults, none of the immunologic variables investigated was specific to cerebral
      malaria or to a fatal outcome.

PMID- 7811868
TI  - Pilot study of azithromycin for treatment of primary and secondary syphilis.
AB  - Azithromycin has in vitro activity against Treponema pallidum and is effective
      against experimental syphilis in rabbits. We undertook an open, noncomparative
      pilot study of oral azithromycin (500 mg once daily for 10 days) to treat 16
      patients with primary or secondary syphilis who were seronegative for human
      immunodeficiency virus. Cure was documented for 11 of 13 patients observed > or =
      3 months; three patients were lost to follow-up. The serological response of one
      patient with secondary syphilis was indeterminate, and one patient with primary
      syphilis had either relapse or reinfection. Four patients had mild
      gastrointestinal side effects, and another patient had an episode of nausea and
      vomiting; all side effects occurred in the first 3 days and resolved
      spontaneously as treatment continued. Azithromycin shows promise as an
      alternative agent for treatment of early syphilis; controlled trials and
      assessment of other dosage regimens are indicated.

PMID- 7811869
TI  - Vitamin A, immunity, and infection.
AB  - Although a role for vitamin A in immunity to infectious diseases has long been
      suggested, only in the last decade have epidemiological, immunologic, and
      molecular studies yielded substantial evidence for a central role. The recent
      discovery of retinoic acid and retinoid X receptors has provided a molecular
      basis for the action of vitamin A and its metabolites at the level of gene
      activation. At least a dozen clinical trials have now demonstrated that vitamin A
      supplementation reduces severe morbidity and mortality from infectious diseases
      among children who have acute measles or who are from areas in which vitamin A
      deficiency is endemic. Vitamin A deficiency is an immunodeficiency disorder
      characterized by widespread alterations in immunity, including pathological
      alterations in mucosal surfaces, impaired antibody responses to challenge with
      protein antigens, changes in lymphocyte subpopulations, and altered T- and B-cell
      function. Vitamin A and its metabolites are immune enhancers that have been shown
      to potentiate antibody responses to T cell-dependent antigens, increase
      lymphocyte proliferation responses to antigens and mitogens, inhibit apoptosis,
      and restore the integrity and function of mucosal surfaces. Vitamin A and related
      retinoids may have potential applications in therapy for some infectious
      diseases.

PMID- 7811870
TI  - Antibody-dependent enhancement of infection and the pathogenesis of viral
      disease.
AB  - Antibody-dependent enhancement of infection (ADE) is an in vitro serological
      phenomenon--or a group of phenomena--in which viral infection of susceptible
      cells is modified by the addition of virus-reactive antibody. Evidence suggests
      that ADE reflects immunologic processes that occur in vivo. Various severe and
      even fatal viral conditions of humans and animals, including dengue shock
      syndrome, the "early-death phenomenon" in experimental infections of immune
      animals, and other vaccine- and immunoglobulin-modified conditions, have been
      attributed to ADE by some researchers. ADE has caused great concern in relation
      to the development of vaccines against dengue virus and human immunodeficiency
      virus. More data are urgently needed on the mechanisms and determinants of ADE
      and on its alleged role in disease pathogenesis and in vaccine-associated
      phenomena.

PMID- 7811871
TI  - Enterocytozoon bieneusi infection in an immunocompetent patient who had acute
      diarrhea and who was not infected with the human immunodeficiency virus.
AB  - Enterocytozoon bieneusi is a microsporidian species that has been detected
      exclusively in patients infected with human immunodeficiency virus (HIV) who are
      severely immunocompromised. We report what we believe is the first case of E.
      bieneusi infection in an HIV-negative patient with acute, self-limited diarrhea
      whose CD4+ cell count was not depressed.

PMID- 7811872
TI  - Microsporidial infections in immunodeficient and immunocompetent patients.
AB  - Microsporidia are obligate, intracellular, spore-forming protozoal parasites.
      Their host range is extensive and includes most invertebrates and all classes of
      vertebrates. Five microsporidial genera (Enterocytozoon, Encephalitozoon,
      Septata, Pleistophora, and Nosema) and unclassified microsporidia have been
      associated with human disease, which appears to manifest primarily in
      immunocompromised persons. The clinical manifestations of microsporidiosis are
      diverse and include intestinal, pulmonary, ocular, muscular, and renal disease.
      The majority of microsporidial infections in persons infected with human
      immunodeficiency virus (HIV) are attributed to Enterocytozoon bieneusi, an
      important cause of chronic diarrhea and wasting. Four cases of microsporidial
      infection among persons not infected with HIV who had documented or presumed
      cellular immunodeficiency and four cases of corneal stroma infection due to
      microsporidia in immunocompetent patients have been described. Furthermore, the
      first case of traveler's diarrhea due to E. bieneusi in an immunocompetent and
      otherwise healthy patient is reported in this issue. The sources of human
      microsporidial infections and modes of transmission are unknown.

PMID- 7811873
TI  - Self-administered antibiotic therapy for chemotherapy-induced, low-risk febrile
      neutropenia in patients with nonhematologic neoplasms.
AB  - A multicenter prospective nonrandomized trial was conducted to evaluate the
      efficacy of self-administered oral ofloxacin in the treatment of cancer patients
      with fever and neutropenia. Patients receiving chemotherapy who either resided
      far away and were unable to reach the oncology ward within 12 hours of the onset
      of fever or were unable to afford the expensive inpatient care were eligible for
      inclusion in the study. Requirements for enrollment included an absolute
      neutrophil count of < or = 0.5 x 10(9)/L, temperature of > 38 degrees C, and the
      ability to take oral medications. The patients were instructed to immediately
      self-administer oral ofloxacin on recognition of fever and to maintain daily
      telephonic contact with the oncology staff. One-hundred eleven such episodes were
      evaluable. Neutropenia was mostly of short duration (87% of episodes, < or = 1
      week); 92 (83%) of the febrile episodes responded to ofloxacin with resolution of
      fever and neutropenia (hospitalization was not required). Two episodes resulted
      in death before the patients could be brought to the hospital; 17 (15%) did not
      respond to ofloxacin, and the patients required hospitalization. The conditions
      of all except one improved with parenteral combination antibiotic therapy. No
      toxicity was observed, and the cost of therapy was negligible. Treatment with
      oral ofloxacin may possibly serve as an alternative to hospitalization for those
      who are otherwise at low risk of morbidity and death.

PMID- 7811874
TI  - The International Tuberculosis Campaign: a pioneering venture in mass vaccination
      and research.
AB  - If an American pediatrician's conversation with Dr. Johannes Holm, a Danish
      pathisiologist and future director of the International Tuberculosis Campaign,
      had not been interrupted, the campaign would probably not have become a
      monumental precedent for world health activities. The International Tuberculosis
      Campaign was conducted under the auspices of the United Nations International
      Children's Emergency Fund and three Scandinavian voluntary organizations. In a
      program that started in the war-torn areas of Europe, nearly 30 million persons
      underwent tuberculin testing, and almost 14 million were given BCG (bacille
      Calmette-Guerin) vaccine. In addition, a postgraduate school for physicians was
      initiated, new laboratories were established and old ones were improved, hundreds
      of young doctors and nurses were introduced to international public health, and,
      perhaps most important, research and service were successfully integrated. The
      success of the campaign led to its becoming the first major disease control and
      research activity of the World Health Organization.

PMID- 7811875
TI  - Fatal gastroenteritis due to Vibrio fluvialis and nonfatal bacteremia due to
      Vibrio mimicus: unusual vibrio infections in two patients.

PMID- 7811876
TI  - Fungemia due to fluconazole-resistant Candida albicans in a patient with AIDS.

PMID- 7811877
TI  - Pneumocystis carinii pneumonia in a patient with chronic obstructive pulmonary
      disease but no evident immunoincompetence.

PMID- 7811878
TI  - Salmonella osteomyelitis complicating an acute fracture in a healthy child.

PMID- 7811879
TI  - Transmission of hepatitis C virus but not human immunodeficiency virus type 1 by
      a human bite.

PMID- 7811880
TI  - Recurrent migraine-like symptoms and hemiplegia precipitated by fever and
      associated with an underlying cerebral arteriovenous malformation.

PMID- 7811881
TI  - Prolonged concurrent use of ganciclovir and foscarnet in the treatment of
      polyradiculopathy due to cytomegalovirus in a patient with AIDS.

PMID- 7811882
TI  - Isolated intramedullary tuberculosis presenting as a conus tumor.

PMID- 7811883
TI  - Hypophyseal tuberculosis in a patient with AIDS.

PMID- 7811884
TI  - Spontaneous bacterial peritonitis due to Streptococcus pneumoniae in a male who
      did not have another concurrent infection.

PMID- 7811885
TI  - Polymicrobial pyomyositis and bacteremia in a patient with AIDS.

PMID- 7811886
TI  - Vibrio cholerae O139 synonym Bengal in Hong Kong.

PMID- 7811887
TI  - Does hospitalizing patients with tuberculosis ensure compliance with drug
      regimens?

PMID- 7811888
TI  - Pulmonary abscess due to non-typhi Salmonella in a patient with AIDS.

PMID- 7811889
TI  - Isolation of Campylobacter fetus subspecies fetus from a gluteal abscess.

PMID- 7811890
TI  - Central venous catheter-related infection due to Comamonas acidovorans in a child
      with non-Hodgkin's lymphoma.

PMID- 7811892
TI  - Transient, asymptomatic bacteremia due to Enterococcus avium in a 33-month-old
      child.

PMID- 7811891
TI  - Relapse of visceral leishmaniasis in patients who were coinfected with human
      immunodeficiency virus and who received treatment with liposomal amphotericin B.

PMID- 7811893
TI  - [The normalization of general medicine/family medicine in Spain].

PMID- 7811894
TI  - [Perversions of primary care].

PMID- 7811895
TI  - [Health council: conclusions after 3-year experience].
AB  - OBJECTIVE: To evaluate the Health Council from 1990 to 1993. To find out what is
      the knowledge and opinion of the Community about Health Council. DESIGN:
      Observational, descriptive and crossover study. SITE. Health Council in El
      Higueron Health Center. Rural population. Cordoba. PARTICIPANTS: Social agents
      and professionals who had participated in the Health Council's meetings during
      the three last years. Community of our suburb. MEASUREMENTS AND MAIN RESULTS: The
      records from three years ago have been analysed. A questionnaire was developed
      and answered in the community. Three focal groups, which had been done with
      social agents and health professional, have been analysed as well. Two groups of
      activities have been discussed: in relation to health problem of the community
      and in relation to Health Center's working. The 70% of them were carried out.
      Social agents took the initiative in 36%. Questionnaire: 92% of community think
      they must participate in the health's problems; 40% of community know the Health
      Council. Focal groups: Health Council is useful for improving the relation
      between Health Center and Community or for getting the Community to participate
      in this subject. CONCLUSIONS: It is important to remain and increase its
      utilization. It is necessary to divulge the Health Council and its function.

PMID- 7811896
TI  - [Menopause and hormone replacement therapy: prevalence in the town of Lugo].
AB  - OBJECTIVE: To discover the use of hormone replacement therapy (HRT) and
      associated variables in the town of Lugo. DESIGN: Crossover study. SETTING: The
      town of Lugo. PATIENTS AND OTHER PARTICIPANTS: A representative sample (506) of
      the women in the town of Lugo between 45 and 65 years old on June 1st 1993, taken
      from the municipal census by means of simple random sampling. INTERVENTIONS: A
      questionnaire, which included questions on gynaecological history, risk factors,
      social/educational level and knowledge and prescription of HRT, was filled in.
      MEASUREMENTS AND MAIN RESULTS: A total of 500 women completed the study. 4.07% of
      the menopausal women (C.I. 95%, 2.6-6.4) received some oestrogen preparation.
      38.8% of the women (C.I. 95%, 34.2-43.5) attended the gynaecologist at least once
      after the menopause. The variable of having gynaecological check-ups was
      associated significantly with having paid employment (p = 0.001) and with a
      higher educational level (p < 0.0001). Out of the 48.9% of the women who knew of
      HRT, less than a quarter had received the information from Health Service staff.
      CONCLUSIONS: The level of use of HRT does not seem in line with its proved
      efficacy. The percentage of women who have gynaecological check-ups after the
      menopause continues to be low. Social and cultural factors, in addition to those
      already described in the literature, are suggested as factors possibly
      conditioning both the above points. Programmes to match menopause care to the
      latest scientific advances should be set up jointly between Primary Care and
      specialists.

PMID- 7811897
TI  - [The levels of knowledge about nonclinical areas which are characteristic of the
      new model of primary care].
AB  - OBJECTIVE: To evaluate the level of knowledge about the non-clinical areas which
      characterise the new model of primary care among doctors and nurses who work in
      primary care teams (PCT); and to identify the most deficient areas of knowledge
      and the variables associated with these lower levels of knowledge. DESIGN: An
      observation study of a crossover kind. SETTING: PCTs of Health Area 1 in Madrid.
      PARTICIPANTS: Doctors and nurses who were working in the 23 PCTs functioning when
      the study was carried out (321 people). MEASUREMENTS AND MAIN RESULTS: Knowledge
      was measured by a self-filled, anonymous questionnaire elaborated by a panel of
      experts. It contained 72 items with correct (C) or false (F) double reply,
      grouped in 12 basic areas of knowledge relating to the non-clinical aspects which
      characterise the new model of primary care (PC). A pilot test was done in a PCT
      in another Area. The data bases were performed on DBASEIII+ and the statistical
      analysis on SPSS v. 4.0. The required level of knowledge through the
      questionnaire as a whole was attained by 41.6% of the professionals. An
      association with the following was noted: Age (p < 0.0001), Profession (p <
      0.005), Year that training ended (p < 0.01), Type of contract (p < 0.005), Nature
      of access to a permanent post (p < 0.0005), postgraduate academic training for
      doctors (p < 0.001) and Residency in Family and Community Medicine (p < 0.009).
      The most deficient areas of knowledge were: Evaluation of procedures and
      programmes (46%), Community Participation (51.6%), the filling-out and
      standardisation of records (55.2%), and the Evaluation of objectives and quality
      control mechanisms. CONCLUSIONS: Knowledge of non-clinical areas is low.

PMID- 7811898
TI  - [Moderate rise of transaminases in asymptomatic patients. An etiologic approach
      from the primary care viewpoint].
AB  - OBJECTIVE: To discover the frequency of presentation, the aetiological
      distribution and clinical importance of a moderate rise in transaminases, which
      were found by chance in patients free from hepatic symptomology who were
      attending primary care clinics. DESIGN: Descriptive study of a crossover type.
      SETTING: La Victoria Health Centre in Valladolid. PATIENTS: The patients attended
      at any of the six general medical clinics between january and june 1993, in whom
      a moderate rise in transaminases was detected by chance and confirmed after a one
      month interval. MEASUREMENTS AND MAIN RESULTS: Hepatic function tests were
      performed on 1,285 patients, in 212 of whom biochemical function was found to be
      disturbed. 137 of these 212 were studied in line with a diagnostic procedure
      worked out in collaboration with the Area specialist, after 75 had been
      eliminated for various reasons. The following aetiological distribution was
      observed: Viral 37.2% (Anti VHC + 30.7%, Ag HBs + 6.5%), ethylic 35.03%,
      metabolic 15.32% and medicinal 8.77%. Hemochromatosis was diagnosed in 2
      patients; and a possible aetiology could not be established in 3. It was possible
      to perform a biopsy on 11 patients, with the suspected aetiology being confirmed
      in all of them. CONCLUSIONS: The likelihood of the primary care doctor correctly
      diagnosing hepatic illnesses is high, given that we could establish an aetiology
      in 97% of cases. The most common aetiologies were viral and ethylic.

PMID- 7811899
TI  - [Determining factors of the quality of prescription measured in intrinsic value
      and its potential use].
AB  - OBJECTIVE: To determine whether the following factors-medical training in family
      practice, age of the doctor, health care organization and percentage of patients
      over 65 years--influence the quality of pharmaceutical prescription as measured
      in terms of its intrinsic value and potential use of the prescription. DESIGN:
      Descriptive cross study. SITE. Regional health authorities of Costa de Ponent.
      Barcelona. PARTICIPANTS: 400 general practitioners throughout the whole of 1992.
      MAIN MEASUREMENTS AND RESULTS: Doctors belonging to the new health system and
      specialising in family practise, present higher intrinsic value and potential use
      of the prescription (statistically confirmed), as well as a greater concentration
      of prescription of the top 100 prescribed medicines. Doctors no more than 40
      years old had better prescription but no statistical differences were found. An
      aged population had nearly no influence. CONCLUSIONS: The characteristics of the
      doctor (organization, training) are conditioning factors in the quality of
      pharmaceutical prescription.

PMID- 7811900
TI  - [Attitude to tobacco and prevalence of smokers among primary care physicians in
      Guipuzcoa].
AB  - OBJECTIVE: To discover the evolvement of Primary Care doctors' tobacco
      consumption in Guipuzcoa and their attitudes to tobacco dependency. DESIGN: A
      descriptive study of a crossover type. October 1992. SETTING: Primary Health
      care. PARTICIPANTS: 381 general physicians and paediatricians from Guipuzcoa
      province. MEASUREMENTS AND MAIN RESULTS: A self-filled questionnaire was
      distributed at Health Centres for subsequent return by mail. The reply rate was
      60.89%, 42.3% were smokers; 33.6%, ex-smokers. 43% of smokers smoked in the
      Centre; 2% in front of patients. We found significant differences (p < 0.05) with
      a study carried out in 1988, where doctors who smoked were 52.4%, ex-smokers 19%
      and doctors who smoked in front of patients, 18.2%. 45.7% of women smoked, 39.2%
      of men. 78% of the doctors under study stated that they questioned patients about
      tobacco consumption. 95.2% did so when patients had specific pathologies.
      CONCLUSIONS: There has been a significant decline in tobacco smoking by doctors
      in Guipuzcoa. There are more women than men smokers. There is a higher proportion
      of ex-smokers among doctors than in the population as a whole. There has been a
      positive change of attitude as to smoking in front of patients. Centres should
      become more involved in the struggle against tobacco by offering to set up
      dependency counselling groups.

PMID- 7811901
TI  - [Evaluation of the DTP vaccination technique in infants].
AB  - OBJECTIVE: To evaluate the techniques of DPT vaccination in the nursing child.
      DESIGN: An observation study of a crossover type. Evaluation by means of an
      anonymous survey of those responsible for administering the vaccinations.
      Statistical analysis using the precise Fisher test. PARTICIPANTS: The thirteen
      official vaccination centres in Health Areas 11 and 12 in the Community of
      Valencia. MEASUREMENTS AND MAIN RESULTS: 12 centres (91%) answered the
      questionnaire. Four of them (41%) used different needles to aspirate the contents
      of the vial and give the injection to the nursing child. The DPT was always
      administered in the gluteal region. 33% used needles which were 16 mm long.
      Prophylactic paracetamol was used in two of the Centres as a matter of course.
      The Centre's size or length of time in use did not affect the techniques used.
      CONCLUSIONS: There is no uniformity in the technique of administering the DPT
      vaccine to the nursing child in the different Vaccination Centres of Areas 11 and
      12 in the Community of Valencia. The techniques used for vaccinations often
      differ from those recommended by groups of experts.

PMID- 7811902
TI  - [Program of medical records management].

PMID- 7811903
TI  - [Teaching of communication and interviewing techniques: the need for a unifying
      model].

PMID- 7811904
TI  - [Care of the people not registered at an urban health center].

PMID- 7811905
TI  - [Who should perform the bureaucratic tasks of medical practice?].

PMID- 7811906
TI  - [Diagnostic agreement between primary care physicians and rheumatologists].

PMID- 7811907
TI  - [The further development of a human, alloplastic tracheal prosthesis].
AB  - The present paper discusses the design, construction and characterization of
      human alloplastic tracheal prostheses. Two different types of construction, the
      spiral and the clasp prosthesis, have been developed. The prostheses are
      composite constructions comprising a silicone tube and a polyethylene
      reinforcement connected together by means of a biocompatible adhesive. The
      results of various mechanical examinations (stress-strain behavior, torsional
      strength, compressibility, bending stiffness, fatigue testing) show that some of
      the 14 prostheses investigated approach the human trachea in terms of mechanical
      properties, and may be considered suitable. Suggestions for further improvements
      are made.

PMID- 7811908
TI  - [Telemetric transmission system for in vivo measurement of the stress load of an
      internal spinal fixator].
AB  - For stabilizing fractures of the spine, a number of implantable devices are
      available. However, not much is known about the loads acting on these devices. In
      order to measure the forces and moments within the implant, the Dick internal
      fixation device was modified and fitted out with a hermetically sealed
      inductively powered telemetry unit. An integrated 8-channel telemetry chip was
      specially developed to measure the signals of six strain gauge sensors, the
      temperature of the implant and the supply voltage. Since the internal fixation
      devices are always implanted in pairs, two telemetry units are operated at the
      same time. This article details the function of the implanted electronic circuit
      and the external system components.

PMID- 7811909
TI  - [Mechanical hemolysis caused by artificial organs--comparison of in vitro
      hemolysis studies and their application to in vivo conditions].
AB  - Changes of plasma concentration are often used for in vitro characterisation of
      the hemolytic potency of artificial organs and apparatus. Different indices of
      hemolysis are derived from Hb concentration, which, in general, depend on
      experimental conditions and cannot be compared quantitatively or used to describe
      the in vivo damage. In this paper we propose a similarity number called "lysis
      number" that is independent of experimental conditions. It describes the
      probability for a single blood cell to be completely destroyed in a single pass
      through the corresponding artificial assist system. The concept is based on the
      steps: 1. Definition of "lysis number" as an index of hemolytic performance of
      artificial organs or implants. 2. Description of more complex hemolytic damaging
      processes (different hemolytic steps) that may be in series or parallel and
      definition of an effective lysis number. 3. Experimental in vitro estimation of
      each of the processes in consecutive steps. 4. Calculation of total hemolysis of
      the complex system using the linkage rules. 5. Application to in vivo by an
      appropriate differential equation in RBC mas taking into account mechanically
      induced hemolysis rate, survival time of normal RBC and erythropoetic generation
      rate.

PMID- 7811910
TI  - Selection of electrode positions for an EEG-based brain computer interface (BCI).
AB  - One major question in designing an EEG-based Brain Computer Interface to bypass
      the normal motor pathways is the selection of proper electrode positions. This
      study investigates electrode selection with a Distinction Sensitive Learning
      Vector Quantizer (DSLVQ). DSLVQ is an extended Learning Vector Quantizer (LVQ)
      which employs a weighted distance function for dynamical scaling and feature
      selection. The data analysed and classified were 56-channel EEG recordings over
      sensorimotor areas during preparation for discrete left or right index finger
      flexions. Data from 3 subjects are reported. It was found by DSLVQ that the most
      important electrode positions for differentiation between planning of left and
      right finger movement overlie cortical finger/hand areas over both hemispheres.

PMID- 7811911
TI  - The saxitoxin/tetrodotoxin binding site on cloned rat brain IIa Na channels is in
      the transmembrane electric field.
AB  - The rat brain IIa (BrIIa) Na channel alpha-subunit and the brain beta 1 subunit
      were coexpressed in Xenopus oocytes, and peak whole-oocyte Na current (INa) was
      measured at a test potential of -10 mV. Hyperpolarization of the holding
      potential resulted in an increased affinity of STX and TTX rested-state block of
      BrIIa Na channels. The apparent half-block concentration (ED50) for STX of BrIIa
      current decreased with hyperpolarizing holding potentials (Vhold). At Vhold of 
      100 mV, the ED50 was 2.1 +/- 0.4 nM, and the affinity increased to a ED50 of 1.2
      +/- 0.2 nM with Vhold of -140 mV. In the absence of toxin, the peak current
      amplitude was the same for all potentials negative to -90 mV, demonstrating that
      all of the channels were in a closed conformation and maximally available to open
      in this range of holding potentials. The Woodhull model (1973) was used to
      describe the increase of the STX ED50 as a function of holding potential. The
      equivalent electrical distance of block (delta) by STX was 0.18 from the
      extracellular milieu when the valence of STX was fixed to +2. Analysis of the
      holding potential dependence of TTX block yielded a similar delta when the
      valence of TTX was fixed to +1. We conclude that the guanidinium toxin site is
      located partially within the transmembrane electric field. Previous site-directed
      mutagenesis studies demonstrated that an isoform-specific phenylalanine in the
      BrIIa channel is critical for high affinity toxin block. Therefore, we propose
      that amino acids at positions corresponding to this Phe in the BrIIa channel,
      which lie in the outer vestibule of the channel adjacent to the pore entrance,are
      partially in the transmembrane potential drop.

PMID- 7811912
TI  - Amine blockers of the cytoplasmic mouth of sodium channels: a small structural
      change can abolish voltage dependence.
AB  - Many drugs block sodium channels from the cytoplasmic end (Moczydlowski, E., A.
      Uehara, X, Guo, and J. Heiny. 1986. Isochannels and blocking modes of voltage
      dependent sodium channels. Ann. N.Y. Acad. Sci. 479:269-292.). Lidocaine, applied
      to either side of the membrane, induces two blocking modes, a rapid, voltage
      dependent open-channel block, and a block of the inactivated channel that occurs
      on a 1000-fold slower timescale. Here we describe the actions of several
      lidocaine-related amines on batrachotoxin(BTX)-activated bovine cardiac sodium
      channels incorporated into planar lipid bilayers. We applied blocking amines from
      the intracellular side and examined the structural determinants of fast, open
      channel block. Neither hydroxyl nor carbonyl groups, present in the aryl-amine
      link of lidocaine, were necessary, indicating that hydrogen bonding between
      structures in the aryl-amine link and the channel is not required. Block,
      however, was significantly enhanced by addition of an aromatic ring, or by the
      lengthening of aliphatic side chains, suggesting that a hydrophobic domain
      strengthens binding while the amine group blocks the pore. For most blockers,
      depolarizing potentials enhanced block, with the charged amine group apparently
      traversing 45-60% of the transmembrane voltage. By contrast, block by
      phenylhydrazine was essentially voltage-independent. The relatively rigid planar
      structure of phenylhydrazine may prevent the charged amino end from entering the
      electric field when the aromatic ring is bound. The relation between structural
      features of different blockers and their sensitivity to voltage suggests that the
      transmembrane voltage drops completely over less than 5 A. We raise the
      possibility that the proposed hydrophobic binding domain overlaps the endogenous
      receptor for the inactivation gate. If so, our data place limits on the distance
      between this receptor and the intrapore site at which charged amines bind.

PMID- 7811913
TI  - Transcainide causes two modes of open-channel block with different voltage
      sensitivities in batrachotoxin-activated sodium channels.
AB  - Transcainide, a complex derivative of lidocaine, blocks the open state of BTX
      activated sodium channels from bovine heart and rat skeletal muscle in two
      distinct ways. When applied to either side of the membrane, transcainide caused
      discrete blocking events a few hundred milliseconds in duration (slow block), and
      a concomitant reduction in apparent single-channel amplitude, presumably because
      of rapid block beyond the temporal resolution of our recordings (fast block). We
      quantitatively analyzed block from the cytoplasmic side. Both modes of block
      occurred via binding of the drug to the open channel, approximately followed 1:1
      stoichiometry, and were similar for both channel subtypes. For slow block, the
      blocking rate increased, and the unblocking rate decreased with depolarization,
      yielding an overall enhancement of block at positive potentials, and suggesting a
      blocking site at an apparent electrical distance about 45% of the way from the
      cytoplasmic end of the channel (z delta approximately 0.45). In contrast, the
      fast blocking mode was only slightly enhanced by depolarization (z delta
      approximately 0.15). Phenomenologically, the bulky and complex transcainide
      molecule combines the almost voltage-insensitive blocking action of
      phenylhydrazine (Zamponi and French, 1994a (companion paper)) with a slow open
      channel blocking action that shows a voltage dependence typical of simpler
      amines. Only the slower blocking mode was sensitive to the removal of external
      sodium ions, suggesting that the two types of block occur at distinct sites. Dose
      response relations were also consistent with independent binding of transcainide
      to two separate sites on the channel.

PMID- 7811914
TI  - Open-channel block by internally applied amines inhibits activation gate closure
      in batrachotoxin-activated sodium channels.
AB  - We have studied the action of several pore-blocking amines on voltage-dependent
      activation gating of batrachotoxin(BTX)-activated sodium channels, from bovine
      heart and rat skeletal muscle, incorporated into planar lipid bilayers. Although
      structurally simpler, the compounds studied show general structural features and
      channel-inhibiting actions that resemble those of lidocaine. When applied to the
      cytoplasmic end of the channel, these compounds cause a rapid, voltage-dependent,
      open-channel block seen as a reduction in apparent single-channel amplitude
      (companion paper). Internal application of phenylpropanolamine, phenylethylamine,
      phenylmethylamine, and diethylamine, as well as causing open-channel block,
      reduces the probability of channel closure, producing a shift of the steady-state
      activation curve toward more hyperpolarizing potentials. These gating effects
      were observed for both cardiac and skeletal muscle channels and were not evoked
      by addition of equimolar N-Methyl-D-Glucamine, suggesting a specific interaction
      of the blockers with the channel rather than a surface charge effect. Kinetic
      analysis of phenylpropanolamine action on skeletal muscle channels indicated that
      phenylpropanolamine reduced the closed probability via two separate mechanisms.
      First, mean closed durations were slightly abbreviated in its presence. Second,
      and more important, the frequency of the gating closures was reduced. This action
      was correlated with the degree, and the voltage dependence, of open-channel
      block, suggesting that the activation gate cannot close while the pore is
      occluded by the blocker. Such a mechanism might underlie the previously reported
      immobilization of gating charge associated with local anesthetic block of
      unmodified sodium channels.

PMID- 7811916
TI  - Electroporation of the photosynthetic membrane: structural changes in protein and
      lipid-protein domains.
AB  - A biological membrane undergoes a reversible permeability increase through
      structural changes in the lipid domain when exposed to high external electric
      fields. The present study shows the occurrence of electric field-induced changes
      in the conductance of the proton channel of the H(+)-ATPase as well as electric
      field-induced structural changes in the lipid-protein domain of photosystem (PS)
      II in the photosynthetic membrane. The study was carried out by analyzing the
      electric field-stimulated delayed luminescence (EPL), which originates from
      charge recombination in the protein complexes of PS I and II of photosynthetic
      vesicles. We established that a small fraction of the total electric field
      induced conductance change was abolished by N,N'-dicyclohexylcarbodiimide (DCCD),
      an inhibitor of the H(+)-ATPase. This reversible electric field-induced
      conductance change has characteristics of a small channel and possesses a
      lifetime < or = 1 ms. To detect electric field-induced changes in the lipid
      protein domains of PS II, we examined the effects of phospholipase A2 (PLA2) on
      EPL. Higher values of EPL were observed from vesicles that were exposed in the
      presence of PLA2 to an electroporating electric field than to a
      nonelectroporating electric field. The effect of the electroporating field was a
      long-lived one, lasting for a period > or = 2 min. This effect was attributed to
      long-lived electric field-induced structural changes in the lipid-protein domains
      of PS II.

PMID- 7811915
TI  - Ca-mediated and independent effects of arachidonic acid on gap junctions and Ca
      independent effects of oleic acid and halothane.
AB  - In Novikoff hepatoma cell pairs studied by double perforated patch clamp (DPPC),
      brief (20 s) exposure to 20 microM arachidonic acid (AA) induced a rapid and
      reversible uncoupling. In pairs studied by double whole-cell clamp (DWCC),
      uncoupling was completely prevented by effective buffering of Cai2+ with BAPTA.
      Similarly, AA (20 s) had no effect on coupling in cells perfused with solutions
      containing no added Ca2+ (SES-no-Ca) and studied by DPPC, suggesting that Ca2+
      influx plays an important role. Parallel experiments monitoring [Ca2+]i with fura
      2 showed that [Ca2+]i increases with AA to 0.7-1.5 microM in normal [Ca2+]o, and
      to approximately 400 nM in SES-no-Ca solutions. The rate of [Ca2+]i increase
      matched that of Gj decrease, but [Ca2+]i recovery was faster. In cells studied by
      DWCC with 2 mM BAPTA in the pipette solution and superfused with SES-no-Ca, long
      exposure (1 min) to 20 microM AA caused a slow and virtually irreversible
      uncoupling. This result suggests that AA has a dual mechanism of uncoupling: one
      dominant, fast, reversible, and Ca(2+)-dependent, the other slow, poorly
      reversible, and Ca(2+)-independent. In contrast, uncoupling by oleic acid (OA) or
      halothane was insensitive to internal buffering with BAPTA, suggesting a Ca(2+)
      independent mechanism only.

PMID- 7811917
TI  - Solute effects on the colloidal and phase behavior of lipid bilayer membranes:
      ethanol-dipalmitoylphosphatidylcholine mixtures.
AB  - By means of the scanning differential calorimetry, x-ray diffractometry, and the
      dynamic light scattering, we have systematically studied the phase and packing
      properties of dipalmitoylphosphatidylcholine vesicles or multibilayers in the
      presence of ethanol. We have also determined the partial ternary phase diagram of
      such dipalmitoylphosphatidylcholine/water/ethanol mixtures. The directly measured
      variability of the structural bilayer parameters implies that ethanol binding to
      the phospholipid bilayers increases the lateral as well as the transverse
      repulsion between the lipid molecules. This enlarges the hydrocarbon tilt (by up
      to 23 degrees) and molecular area (by < or = 40%). Ethanol-phospholid association
      also broadens the interface and, thus, promotes lipid headgroup solvation. This
      results in excessive swelling (by 130%) of the phosphatidylcholine bilayers in
      aqueous ethanol solutions. Lateral bilayer expansion, moreover, provokes a
      successive interdigitation of the hydrocarbon chains in the systems with bulk
      ethanol concentrations of 0.4-1.2 M. The hydrocarbon packing density as well as
      the propensity for the formation of lamellar gel phases simultaneously increase.
      The pretransition temperature of phosphatidylcholine bilayers is more sensitive
      to the addition of alcohol (initial shift: delta Tp = 22 degrees C/mol) than the
      subtransition temperature (delta Ts reversible 5 degrees C/mol), whereas the
      chain-melting phase transition temperature is even less affected (delta Tm = 1.8
      degrees C/mol). After an initial decrease of 3 degrees for the bulk ethanol
      concentrations below 1.2 M, the Tm value increases by 2.5 degrees above this
      limiting concentration. The gel-phase phosphatidylcholine membranes below Tm are
      fully interdigitated above this limiting concentration. The chain tilt on the
      fringe of full chain interdigitation is zero and increases with higher ethanol
      concentrations. Above Tm, some of the lipid molecules are solubilized by the
      bound ethanol molecules. More highly concentrated ethanol solutions (> 7 M)
      solubilize the phosphatidylcholine bilayers with fluid chains fully and result in
      the formation of mixed lipid-alcohol micelles.

PMID- 7811918
TI  - Surface biophysics of the surface monolayer theory is incompatible with regional
      lung function.
AB  - The surface monolayer theory of Clements was tested on open surface films of calf
      lung surfactant extract in a leak-free vertical film surface balance in which
      alveolar area (A) changes in each lung zone were simulated in accordance with the
      theory. We found that: 1) physiologically necessary low surface tension (gamma),
      < 4 dyn/cm, was sustained only by continuous film compression ("expiration"); 2)
      compression from A equivalent to total lung capacity to functional residual
      capacity produced fleeting gamma reduction in all zones and quick reversal to
      high gamma with A changes that simulated tidal volume (VT) breathing at both 14
      (adult) and 40 (neonatal) cpm; 3) phase differences between gamma and A axes of
      VT loops that indicate mixed surface film composition may be attributable to film
      inertia and viscoelasticity; 4) estimated alveolar retraction pressure due to
      gamma (P gamma) exceeds "net" transpulmonary pressure, i.e., favors alveolar
      collapse, under virtually all conditions of the theory in all zones; 5) return to
      transient, fleeting low gamma in successive VT cycles was determined by the
      inherent difference in compression and decompression rates, which results in
      exhaustion of available A in very few cycles; 6) the "sigh", which restores
      stable low gamma according to the theory, actually produced unstable high gamma
      during virtually all phases of the maneuver. In contrast, closed bubble films of
      the surfactant were structurally stable and produce stable near 0 gamma and P
      gamma.

PMID- 7811919
TI  - Thermotropic phase properties of 1,2-di-O-tetradecyl-3-O-(3-O-methyl- beta-D
      glucopyranosyl)-sn-glycerol.
AB  - The hydration properties and the phase structure of 1,2-di-O-tetradecyl-3-O(3-O
      methyl-beta-D-glucopyranosyl)-sn-glycerol (3-O-Me-beta-D-GlcDAIG) in water have
      been studied via differential scanning calorimetry, 1H-NMR and 2H-NMR
      spectroscopy, and x-ray diffraction. Results indicate that this lipid forms a
      crystalline (Lc) phase up to temperatures of 60-70 degrees C, where a transition
      through a metastable reversed hexagonal (Hll) phase to a reversed micellar
      solution (L2) phase occurs. Experiments were carried out at water concentrations
      in a range from 0 to 35 wt%, which indicate that all phases are poorly hydrated,
      taking up < 5 mol water/mol lipid. The absence of a lamellar liquid crystalline
      (L alpha) phase and the low levels of hydration measured in the discernible
      phases suggest that the methylation of the saccharide moiety alters the hydrogen
      bonding properties of the headgroup in such a way that the 3-O-Me-beta-D-GlcDAIG
      headgroup cannot achieve the same level of hydration as the unmethylated form.
      Thus, in spite of the small increase in steric bulk resulting from methylation,
      there is an increase in the tendency of 3-O-Me-beta-D-GlcDAIG to form nonlamellar
      structures. A similar phase behavior has previously been observed for the
      Acholeplasma laidlawii A membrane lipid 1,2-diacyl-3-O-(6-O-acyl-alpha-D
      glucopyranosyl)-sn-glycerol in water (Lindblom et al. 1993. J. Biol. Chem.
      268:16198-16207). The phase behavior of the two lipids suggests that hydrophobic
      substitution of a hydroxyl group in the sugar ring of the glucopyranosylglycerols
      has a very strong effect on their physicochemical properties, i.e., headgroup
      hydration and the formation of different lipid aggregate structures.

PMID- 7811920
TI  - Membrane solubilization by a hydrophobic polyelectrolyte: surface activity and
      membrane binding.
AB  - We have previously observed that the hydrophobic polyelectrolyte poly(2
      ethylacrylic acid) solubilizes lipid membranes in a pH-dependent manner, and we
      have exploited this phenomenon to prepare lipid vesicles that release their
      contents in response to pH, light, or glucose (Thomas, J. L., and D. A. Tirrell.
      Acc. Chem. Res. 25:336-342, 1992). The physical basis for the interaction between
      poly(2-ethylacrylic acid) and lipid membranes has been explored using surface
      tensiometry and fluorimetry. Varying the polymer concentration results in changes
      in surface activity and membrane binding that correlate with shifts in the
      critical pH for membrane solubilization. Furthermore, the binding affinity is
      reduced as the amount of bound polymer increases. These results are consistent
      with a hydrophobically driven micellization process, similar to those observed
      with apolipoproteins, melittin, and other amphiphilic alpha-helix-based
      polypeptides. The absence of specific secondary structure in the synthetic
      polymer suggests that amphiphilicity, rather than structure, is the most
      important factor in membrane micellization by macromolecules.

PMID- 7811921
TI  - A conformation transition of lung surfactant lipids probably involved in
      respiration.
AB  - X-ray scattering and freeze-fracture electron microscopy of a lung surfactant
      extract show the existence of a complex lamellar phase, L gamma, over a wide
      range of concentrations and temperatures. This lamellar phase, which consists of
      two bilayer motifs comprised of monolayers with stiff chains alternating with
      monolayers with disordered chains, allows us to propose a structural model of a
      collapse phase at the alveolar pulmonary interface. This model accounts for the
      increase in surface pressure during the compression as well as the easy
      respreading upon expansion of the interface during the respiratory cycle.

PMID- 7811922
TI  - Use of an oriented transmembrane protein to probe the assembly of a supported
      phospholipid bilayer.
AB  - Planar-supported phospholipid bilayers formed by the adsorption of vesicles are
      increasingly used in the investigation of lipid-dependent reactions. We have
      studied the way in which these bilayers are formed with phospholipid vesicles
      containing the transmembrane protein Tissue Factor (TF). TF complexed with the
      serine protease, factor VIIa, is the primary initiator of blood coagulation by
      way of activation of the zymogen factor X. TF has been shown to orient randomly
      on the inner and outer leaflets of vesicles. We used proteolytic digestion to
      produce vesicles in which the extracellular domain of TF is located on the inner
      leaflet. These vesicles show no cofactor activity for factor VIIa as a result of
      the inability of the extracellular domain of TF to bind VIIa. After
      freeze/thawing, 50% of the cofactor activity was regained, indicating
      reorientation of the sequestered, inner leaflet TF. Adsorption of these vesicles
      to the inner surface of glass microcapillaries results in a continuous
      phospholipid bilayer. The microcapillaries were perfused with a solution of
      factors VIIa and X, and the effluent was monitored for factor Xa production, a
      sensitive measure of the activity of the TF-VIIa complex. For coatings produced
      with the digested vesicles, minimal TF-VIIa activity was observed, showing that
      the supported bilayer preserves the orientation of the leaflets in the vesicles,
      i.e., the outer leaflet of the vesicles forms the outer leaflet of the supported
      bilayer.

PMID- 7811923
TI  - Kinetic study of the aggregation and lipid mixing produced by alpha-sarcin on
      phosphatidylglycerol and phosphatidylserine vesicles: stopped-flow light
      scattering and fluorescence energy transfer measurements.
AB  - alpha-Sarcin is a fungal cytotoxic protein that inactivates the eukaryotic
      ribosomes. A kinetic study of the aggregation and lipid mixing promoted by this
      protein on phosphatidylglycerol (PG) and phosphatidylserine (PS) vesicles has
      been performed. Egg yolk PG, bovine brain PS, dimyristoyl-PG (DMPG) and
      dimyristoyl-PS (DMPS) vesicles have been considered. The initial rates of the
      vesicle aggregation induced by the protein have been measured by stopped-flow 90
      degrees light scattering. The formation of a vesicle dimer as the initial step of
      this process was deduced from the second-order dependence of the initial rates on
      phospholipid concentration. The highest alpha-sarcin concentration studied did
      not inhibit the vesicle aggregation, indicating that many protein molecules are
      involved in the vesicle cross-linking. These are common characteristics of the
      initial steps of the aggregation produced by alpha-sarcin in the four types of
      phospholipid vesicles considered. However, the kinetics of the scattering values
      revealed that more complex changes occurred in the later steps of the aggregation
      process of egg PG and brain PS vesicles than in those of their synthetic
      counterparts. alpha-Sarcin produced lipid mixing in vesicles composed of DMPG or
      DMPS, which was measured by fluorescence resonance energy transfer assays. A
      delay in the onset of the process, dependent on the protein concentration, was
      observed. Measurement of the rates of lipid mixing revealed that the process is
      first order on phospholipid concentration. Egg PG and brain PS vesicles did not
      show lipid mixing, although they avidly aggregated. However, alpha-sarcin was
      able to promote lipid mixing in heterogeneous systems composed of egg PG+DMPG or
      brain PS+DMPS vesicles. The dilution of the fluorescence probes was faster when
      these were incorporated into the bilayers made of synthetic phospholipids than
      were present in those made of natural phospholipids. The bilayer destabilization
      produced by the protein in the vesices composed of the dimyristoyl-phospholipids
      should be transmitted to the more stable ones made of natural phospholipids. The
      obtained results are interpreted in terms of lipid mixing occurring within
      vesicle aggregates larger than dimer.

PMID- 7811924
TI  - Supported phospholipid/alkanethiol biomimetic membranes: insulating properties.
AB  - A novel model lipid bilayer membrane is prepared by the addition of phospholipid
      vesicles to alkanethiol monolayers on gold. This supported hybrid bilayer
      membrane is rugged, easily and reproducibly prepared in the absence of organic
      solvent, and is stable for very long periods of time. We have characterized the
      insulating characteristics of this membrane by examining the rate of electron
      transfer and by impedance spectroscopy. Supported hybrid bilayers formed from
      phospholipids and alkanethiols are pinhole-free and demonstrate measured values
      of conductivity and resistivity which are within an order of magnitude of that
      reported for black lipid membranes. Capacitance values suggest a dielectric
      constant of 2.7 for phospholipid membranes in the absence of organic solvent. The
      protein toxin, melittin, destroys the insulating capability of the phospholipid
      layer without significantly altering the bilayer structure. This model membrane
      will allow the assessment of the effect of lipid membrane perturbants on the
      insulating properties of natural lipid membranes.

PMID- 7811925
TI  - Functional multiplicity of motor molecules revealed by a simple kinetic analysis.
AB  - We present a simple analytical solution for a kinetic model of motor molecule
      function with multiple arms. This model has a rate of motion proportional to the
      probability that all arms in a complex are detached from the cytoskeleton and,
      therefore, we refer to it as obligate cooperativity. The model has the form: v =
      Vmax/(1 + q/S)n, where Vmax is the maximum velocity, the product nq is the
      effective Michaelis constant at high [ATP], and n is the number of arms. Values
      of n = 2 and n = 1 give good fits to the heavy meromyosin and myosin S1 sliding
      velocity data, respectively, consistent with the number of active sites. Despite
      the complexity of the eukaryotic axoneme, beat frequency data from Chlamydomonas
      wild-type and oda mutants are also fit by this model.

PMID- 7811926
TI  - A birefringence study of changes in myosin orientation during relaxation of
      skinned muscle fibers induced by photolytic ATP release.
AB  - The birefringence of isolated skinned fibers from rabbit psoas muscle was
      measured continuously during relaxation from rigor produced by photolysis of
      caged ATP at sarcomere length 2.8-2.9 microns, ionic strength 0.1 M, 15 degrees
      C. Birefringence, the difference in refractive index between light components
      polarized parallel and perpendicular to the fiber axis, depends on the average
      degree of alignment of the myosin head domain with the fiber axis. After ATP
      release birefringence increased by 5.8 +/- 0.7% (mean +/- SE, n = 6) with two
      temporal components. A small fast component had an amplitude of 0.9 +/- 0.2% and
      rate constant of 63 s-1. By the completion of this component, the instantaneous
      stiffness had decreased to about half the rigor value, and the force response to
      a step stretch showed a rapid (approximately 1000 s-1) recovery phase.
      Subsequently a large slow birefringence component with rate constant 5.1 s-1
      accompanied isometric force relaxation. Inorganic phosphate (10 mM) did not
      affect the fast birefringence component but accelerated the slow component and
      force relaxation. The fast birefringence component was probably caused by
      formation of myosin.ATP or myosin.ADP.Pi states that are weakly bound to actin.
      The average myosin head orientation at the end of this component is slightly more
      parallel to the fiber axis than in rigor.

PMID- 7811927
TI  - Fourier analysis of wing beat signals: assessing the effects of genetic
      alterations of flight muscle structure in Diptera.
AB  - A method for determining and analyzing the wing beat frequency in Diptera is
      presented. This method uses an optical tachometer to measure Diptera wing
      movement during flight. The resulting signal from the optical measurement is
      analyzed using a Fast Fourier Transform (FFT) technique, and the dominant
      frequency peak in the Fourier spectrum is selected as the wing beat frequency.
      Also described is a method for determining quantitatively the degree of
      variability of the wing beat frequency about the dominant frequency. This method
      is based on determination of a quantity called the Hindex, which is derived using
      data from the FFT analysis. Calculation of the H index allows computer-based
      selection of the most suitable segment of recorded data for determination of the
      representative wing beat frequency. Experimental data suggest that the H index
      can also prove useful in examining wing beat frequency variability in Diptera
      whose flight muscle structure has been genetically altered. Examples from
      Drosophila indirect flight muscle studies as well as examples of artificial data
      are presented to illustrate the method. This method fulfills a need for a
      standardized method for determining wing beat frequencies and examining wing beat
      frequency variability in insects whose flight muscles have been altered by
      protein engineering methods.

PMID- 7811928
TI  - A comparison of the second harmonic generation from light-adapted, dark-adapted,
      blue, and acid purple membrane.
AB  - The second order nonlinear polarizability and dipole moment changes upon light
      excitation of light-adapted bacteriorhodopsin (BR), dark-adapted BR, blue
      membrane, and acid purple membrane have been measured by second harmonic
      generation. Our results indicate that the dipole moment changes of the retinal
      chromophore, delta mu, are very sensitive to both the chromophore structure and
      protein/chromophore interactions. Delta mu of light-adapted BR is larger than
      that of dark-adapted BR. The acid-induced formation of the blue membrane results
      in an increase in the delta mu value, and formation of acid purple membrane,
      resulting from further reduction of pH to 0, returns the delta mu to that of
      light-adapted BR. The implications of these findings are discussed.

PMID- 7811929
TI  - Facilitation of the responses to injections of inositol 1,4,5-trisphosphate
      analogs in Limulus ventral photoreceptors.
AB  - Injection of inositol 1,4,5-trisphosphate and its metabolically resistant analogs
      InsP3S3 and L-chiro-2,3,5-InsP3 into the ventral photoreceptors of Limulus
      results in the release of calcium from internal stores and in a current flow into
      the cells. We show here that the dependence of the current response on the amount
      of analog injected is supralinear. The injections also facilitate the responses
      to subsequent injections. We analyze the kinetics of the responses either by very
      slow application of the analogs directly into the lobe that is sensitive to InsP3
      and light or by delivering a pulse into the nonsensitive lobe of the cell, in
      both cases creating a ramp of rising concentration in the sensitive region.
      Typically, a long latent period was followed by a strong brief inward current.
      The ratio between the latency and the duration of the response, defined as twice
      the time from half-amplitude to the peak of the response, reaches values greater
      than 10. Our analysis shows that this value cannot be attained within realistic
      models whose only nonlinearity is the cooperative binding of the ligand to its
      receptor. The observed ratio, however, can be achieved with a positive feedback
      model. Treatments that lead to partial depletion of calcium stores reversibly
      increase the latency of the response. We conclude that the mechanisms of the
      response of Limulus ventral eye to the metabolically resistant analogs of InsP3
      probably involves a positive feedback mechanism and that the carrier of the
      feedback is likely to be Ca2+.

PMID- 7811931
TI  - The bacteriorhodopsin photocycle: direct structural study of two substrates of
      the M-intermediate.
AB  - Changes in protein structure that occur during the formation of the M
      photointermediate of bacteriorhodopsin can be directly visualized by electron
      diffraction techniques. A modified preparation technique for glucose-embedded
      crystals was employed to ensure sufficient hydration of the crystals, which was
      needed for the formation of the M intermediate at low temperature. Samples
      containing a high percentage of the M intermediate were trapped by rapidly
      cooling the crystals with liquid nitrogen after illumination with filtered green
      light at 240 and 260 K, respectively. Difference Fourier projection maps are
      presented for the M intermediates formed at these two temperatures. The
      diffraction data clearly show that statistically significant structural changes
      occur upon formation of the M intermediate at 240 K and then further upon
      formation of the second specimen that is produced at 260 K.

PMID- 7811932
TI  - Met-145 is a key residue in the dark adaptation of bacteriorhodopsin homologs.
AB  - Composition of retinal isomers in three proton pumps (bacteriorhodopsin,
      archaerhodopsin-1, and archaerhodopsin-2) was determined by high performance
      liquid chromatography in their light-adapted and dark-adapted states. In the
      light-adapted state, more than 95% of the retinal in all three proton pumps were
      in the all-trans configuration. In the dark-adapted state, there were only two
      retinal isomers, all-trans and 13-cis, in the ratio of all-trans: 13-cis = 1:2
      for bacteriorhodopsin, 1:1 for archaerhodopsin-1, and 3:1 for archaerhodopsin-2.
      The difference in the final isomer ratios in the dark-adapted bacteriorhodopsin
      and archaerhodopsin-2 was ascribed to the methionine-145 in bacteriorhodopsin.
      This is the only amino acid in the retinal pocket that is substituted by
      phenylalanine in archaerhodopsin-2. The bacteriorhodopsin point-mutated at this
      position to phenylalanine dramatically altered the final isomer ratio from 1:2 to
      3:1 in the dark-adapted state. This point mutation also caused a 10 nm blue-shift
      of the adsorption spectrum, which is similar to the shift of archaerhodopsin-2
      relative to the spectra of bacteriorhodopsin and archaerhodopsin-1.

PMID- 7811930
TI  - Two progressive substrates of the M-intermediate can be identified in glucose
      embedded, wild-type bacteriorhodopsin.
AB  - Glucose-embedded bacteriorhodopsin shows M-intermediates with different Amide I
      infrared bands when samples are illuminated at 240 or 260 K, in contrast with
      fully hydrated samples where a single M-intermediate is formed at all
      temperatures. In hydrated, but not in glucose-embedded specimens, the N
      intermediate is formed together with M at 260 K. Both Fourier transform infrared
      and electron diffraction data from glucose-embedded bacteriorhodopsin suggest
      that at 260 K a mixture is formed of the M-state that is trapped at 240 K, and a
      different M-intermediate (MN) that is also formed by mutant forms of
      bacteriorhodopsin that lack a carboxyl group at the 96 position, necessary for
      the M to N transition. The fact that an MN species is trapped in glucose
      embedded, wild-type bacteriorhodopsin suggests that the glucose samples lack
      functionally important water molecules that are needed for the proton transfer
      aspartate 96 to the Schiff base (and, thus, to form the N-intermediate); thus,
      aspartate 96 is rendered ineffective as a proton donor.

PMID- 7811933
TI  - Time-resolved room temperature protein phosphorescence: nonexponential decay from
      single emitting tryptophans.
AB  - The single room temperature phosphorescent (RTP) residue of horse liver alcohol
      dehydrogenase (LADH). Trp-314, and of alkaline phosphatase (AP), Trp-109, show
      nonexponential phosphorescence decays when the data are collected to a high
      degree of precision. Using the maximum entropy method (MEM) for the analysis of
      these decays, it is shown that AP phosphorescence decay is dominated by a single
      Gaussian distribution, whereas for LADH the data reveal two amplitude packets.
      The lifetime-normalized width of the MEM distribution for both proteins is larger
      than that obtained for model monoexponential chromophores (e.g., terbium in water
      and pyrene in cyclohexane). Experiments show that the nonexponential decay is
      fundamental; i.e., an intrinsic property of the pure protein. Because
      phosphorescence reports on the state of the emitting chromophore, such
      nonexponential behavior could be caused by the presence of excited state
      reactions. However, it is also well known that the phosphorescence lifetime of a
      tryptophan residue is strongly dependent on the local flexibility around the
      indole moiety. Hence, the nonexponential phosphorescence decay may also be caused
      by the presence of at least two states of different local rigidity (in the
      vicinity of the phosphorescing tryptophan) corresponding to different ground
      state conformers. The observation that in the chemically homogeneous LADH sample
      the phosphorescence decay kinetics depends on the excitation wavelength further
      supports this latter interpretation. This dependence is caused by the wavelength
      selective excitation of Trp-314 in a subensemble of LADH molecules with differing
      hydrophobic and rigid environments. With this interpretation, the data show that
      interconversion of these states occurs on a time scale long compared with the
      phosphorescence decay (0.1-1.0 s). Further experiments reveal that with
      increasing temperature the distributed phosphorescence decay rates for both AP
      and LADH broaden, thus indicating that either 1) the number of conformational
      states populated at higher temperature increases or 2) the temperature
      differentially affects individual conformer states. The nature of the observed
      heterogeneous triplet state kinetics and their relationship to aspects of protein
      dynamics are discussed.

PMID- 7811934
TI  - NuMA/centrophilin: sequence analysis of the coiled-coil rod domain.
AB  - Nuclear mitotic apparatus protein (NuMA), also known as centrophilin, has been
      shown in previous work to contain a centrally located sequence of length 1485
      residues that has both a heptad substructure and a high propensity for alpha
      helix formation. Further analysis of this sequence here has revealed that NuMA
      will form a two-stranded coiled-coil structure with multiple (18) points at which
      the conformation is interrupted either by proline-containing segments or by
      discontinuities in the phasing of the heptad substructure. It has also been shown
      that the two chains will be parallel (rather than antiparallel), that they will
      lie in axial register, and that this arrangement will be stabilized by a large
      number of interchain ionic interactions. Interestingly the coiled-coil rod domain
      is also shown to lack any significant long-range periodicity in the linear
      distribution of either its acidic or its basic residues. Hence there is no direct
      evidence from the sequence data that NuMA molecules will aggregate to form
      closely packed filaments within nuclear space.

PMID- 7811935
TI  - Solution conformation of cytochrome c-551 from Pseudomonas stutzeri ZoBell
      determined by NMR.
AB  - 1H NMR spectroscopy and solution structure computations have been used to examine
      ferrocytochrome c-551 from Pseudomonas stutzeri ZoBell (ATCC 14405). Resonance
      assignments are proposed for all main-chain and most side-chain protons.
      Stereospecific assignments were also made for some of the beta-methylene protons
      and valine methyl protons. Distance constraints were determined based upon
      nuclear Overhauser enhancements between pairs of protons. Dihedral angle
      constraints were determined from estimates of scalar coupling constants and intra
      residue NOEs. Twenty structures were calculated by distance geometry and refined
      by energy minimization and simulated annealing on the basis of 1012 interproton
      distance and 74 torsion angle constraints. Both the main-chain and side-chain
      atoms are well defined except for two terminal residues, and some side-chain
      atoms located on the molecular surface. The average root mean squared deviation
      in the position for equivalent atoms between the 20 individual structures and the
      mean structure obtained by averaging their coordinates is 0.56 +/- 0.10 A for the
      main-chain atoms, and 0.95 +/- 0.09 A for all nonhydrogen atoms of residue 3 to
      80 plus the heme group. The average structure was compared with an analogous
      protein, cytochrome c-551 from pseudomonas stutzeri. The main-chain folding
      patterns are very consistent, but there are some differences, some of which can
      be attributed to the loss of normally conserved aromatic residues in the ZoBell c
      551.

PMID- 7811936
TI  - Amyloid-beta aggregation: selective inhibition of aggregation in mixtures of
      amyloid with different chain lengths.
AB  - One of the clinical manifestations of Alzheimer's disease is the deposition of
      the 39-43 residue amyloid-beta (A beta) peptide in aggregated fibrils in senile
      plaques. Characterization of the aggregation behavior of A beta is one of the
      critical issues in understanding the role of A beta in the disease process. Using
      solution hydrodynamics, A beta was observed to form three types of species in
      phosphate-buffered saline: insoluble aggregates with sedimentation coefficients
      of approximately 50,000 S and molecular masses of approximately 10(9) Da,
      "soluble aggregates" with sedimentation coefficients of approximately 30 S and
      masses of approximately 10(6) Da, and monomer. When starting from monomer, the
      aggregation kinetics of A beta 1-40 (A beta 40) and A beta 1-42 (A beta 42),
      alone and in combination, reveal large differences in the tendency of these
      peptides to aggregate as a function of pH and other solution conditions. At pH
      4.1 and 7.0-7.4, aggregation is significantly slower than at pH 5 and 6. Under
      all conditions, aggregation of the longer A beta 42 was more rapid than A beta
      40. Oxidation of Met-35 to the sulfoxide in A beta 40 enhances the aggregation
      rate over that of the nonoxidized peptide. Aggregation was found to be dependent
      upon temperature and to be strongly dependent on peptide concentration and ionic
      strength, indicating that aggregation is driven by a hydrophobic effect. When A
      beta 40 and A beta 42 are mixed together, A beta 40 retards the aggregation of A
      beta 42 in a concentration-dependent manner. Shorter fragments have a decreasing
      ability to interfere with A beta 42 aggregation. Conversely, the rate of
      aggregation of A beta 40 can be significantly enhanced by seeding slow
      aggregating solutions with preformed aggregates of A beta 42. Taken together, the
      inhibition of A beta 42 aggregation by A beta 40, the seeding of A beta 40
      aggregation by A beta 42 aggregates, and the chemical oxidation of A beta 40
      suggest that the relative abundance and rates of production of different-length A
      beta and its exposure to radical damage may be factors in the accumulation of A
      beta in plaques in vivo.

PMID- 7811937
TI  - Biologically addressable monolayer structures formed by templates of sulfur
      bearing molecules.
AB  - We demonstrate that the combined application of Langmuir-Blodgett and self
      assembly techniques allows the fabrication of patterns with contrasting surface
      properties on gold substrates. The process is monitored using fluorescence
      microscopy and surface plasmon spectroscopy and microscopy. These structures are
      suitable for the investigation of biochemical processes at surfaces and in
      ultrathin films. Two examples of such processes are shown. In the first example,
      the structures are addressed through the binding of a monoclonal antibody to a
      peptide. This demonstrates the formation of self-assembled monolayers by cysteine
      bearing peptides on gold, and the directed binding of proteins to the structured
      layers. A high contrast between specific and unspecific binding of proteins is
      observed by the patterned presentation of antigens. Such films possess
      considerable potential for the design of multichannel sensor devices. In the
      second example, a structured phospholipid layer is produced by controlled self
      assembly from vesicle solution. The structures created--areas of phospholipid
      bilayer, surrounded by a matrix of phospholipid monolayer--allow formation of a
      supported bilayer which is robust and strongly bound to the gold support, with
      small areas of free-standing bilayer which very closely resemble a phospholipid
      cell membrane.

PMID- 7811938
TI  - Effect of acid predissolution on fibril size and fibril flexibility of synthetic
      beta-amyloid peptide.
AB  - beta-amyloid peptide (A beta) is the major protein component of senile plaques
      and cerebrovascular amyloid deposits in Alzheimer's patients. Several researchers
      have demonstrated that A beta is neurotoxic in in vitro and in vivo systems.
      Peptide aggregation state and/or conformation might play a significant role in
      determining the toxicity of the peptide. The size and flexibility of fibrils
      formed from the synthetic peptide beta (1-39), corresponding to the first 39
      residues of A beta, were determined. Samples were prepared either directly from
      lyophilized peptide or diluted from a 10 mg/ml stock solution in 0.1%
      trifluoroacetic acid (TFA). All samples had a final peptide concentration of 0.5
      mg/ml, a final pH of 7.4, and a final NaCl concentration of 0.14 M. The molecular
      weight and linear density of the fibrils increased with increasing pre-incubation
      time in TFA, based on static light scattering measurements. Analysis of the
      angular dependence of the intensity of scattered light indicated that the fibrils
      were semi-flexible chains and that the fibril flexibility decreased with
      increasing pre-incubation time in TFA. There was a concomitant change in phase
      behavior from precipitation to gelation with the decrease in fibril flexibility.

PMID- 7811939
TI  - Recognition and processing of randomly fluctuating electric signals by Na,K
      ATPase.
AB  - Previous work has shown that Na,K-ATPase of human erythrocytes can extract free
      energy from sinusoidal electric fields to pump cations up their respective
      concentration gradients. Because regularly oscillating waveform is not a feature
      of the transmembrane electric potential of cells, questions have been raised
      whether these observed effects are biologically relevant. Here we show that a
      random-telegraph fluctuating electric field (RTF) consisting of alternating
      square electric pulses with random lifetimes can also stimulate the Rb(+)-pumping
      mode of the Na,K-ATPase. The net RTF-stimulated, ouabain-sensitive Rb+ pumping
      was monitored with 86Rb+. The tracer-measured, Rb+ influx exhibited frequency and
      amplitude dependencies that peaked at the mean frequency of 1.0 kHz and amplitude
      of 20 V/cm. At 4 degrees C, the maximal pumping activity under these optimal
      conditions was 28 Rb+/RBC-hr, which is approximately 50% higher than that
      obtained with the sinusoidal electric field. These findings indicate that Na,K
      ATPase can recognize an electric signal, either regularly oscillatory or randomly
      fluctuating, for energy coupling, with high fidelity. The use of RTF for
      activation also allowed a quantitative theoretical analysis of kinetics of a
      membrane transport model of any complexity according to the theory of
      electroconformational coupling (ECC) by the diagram methods. A four-state ECC
      model was shown to produce the amplitude and the frequency windows of the Rb(+)
      pumping if the free energy of interaction of the transporter with the membrane
      potential was to include a nonlinear quadratic term. Kinetic constants for the
      ECC model have been derived. These results indicate that the ECC is a plausible
      mechanism for the recognition and processing of electric signals by proteins of
      the cell membrane.

PMID- 7811940
TI  - An estimated shape function for drift in a platelet-transport model.
AB  - Prior work has shown that concentration profiles of platelets in flowing whole
      blood and of platelet-sized beads in flowing blood suspensions can include near
      wall excesses. A model to describe this phenomenon was built about a single
      component convective diffusion equation. To incorporate redistribution to
      preferred sites by shear flows of red cell suspensions, the model used a drift
      shape function (in addition to the commonly used augmented diffusion
      coefficient). This paper reports experiments that provide an average
      concentration profile from which the shape function for that model is calculated;
      the experiments and shape function are for the particular conditions of 40%
      hematocrit, platelet-sized latex beads (2.5 microns diameter), tube ID of 217
      microns, and a wall shear rate of 555 s-1. Less precise estimates of the shape
      function obtained from data of previous studies indicate that the shape function
      is similar for the hematocrit of 15%.

PMID- 7811941
TI  - Transient state kinetics tutorial using the kinetics simulation program, KINSIM.
AB  - This article provides an introduction to a computer tutorial on transient state
      kinetics. The tutorial uses our Macintosh version of the computer program,
      KINSIM, that calculates the time course of reactions. KINSIM is also available
      for other popular computers. This program allows even those investigators not
      mathematically inclined to evaluate the rate constants for the transitions
      between the intermediates in any reaction mechanism. These rate constants are one
      of the insights that are essential for understanding how biochemical processes
      work at the molecular level. The approach is applicable not only to enzyme
      reactions but also to any other type of process of interest to biophysicists,
      cell biologists, and molecular biologists in which concentrations change with
      time. In principle, the same methods could be used to characterize time
      dependent, large-scale processes in ecology and evolution. Completion of the
      tutorial takes students 6-10 h. This investment is rewarded by a deep
      understanding of the principles of chemical kinetics and familiarity with the
      tools of kinetics simulation as an approach to solve everyday problems in the
      laboratory.

PMID- 7811942
TI  - Simultaneous 280 MHz EPR imaging of rat organs during nitroxide free radical
      clearance.
AB  - A radio frequency (RF) (280 MHz) electron paramagnetic resonance (EPR)
      spectroscopy and imaging apparatus has been used to localize a pyrrolidine
      nitroxide free radical in the rat abdomen and thorax. The nitroxide 2,2.5.5,
      tetramethylpyrrolidine-1-oxyl-3- carboxylic acid (PCA) had a whole body
      monoexponential decay with half-life of 13.3 +/- 0.7 (n = 4), 19.4 +/- 0.2 (n =
      3), and 23 +/- 2 (n = 6) min for 1, 2, and 3 mmol/kg PCA, respectively. Up to
      seven one-dimensional longitudinal projections were collected on six rats in the
      presence of a 8 mT/m field gradient. With an injection dose of 3 mmol/kg, PCA
      half-lives were 19 +/- 1, 17 +/- 2, and 22 +/- 2 min (n = 6) in the lower
      abdomen, in the liver, and in the thorax, respectively. Thorax half-life was
      significantly longer than liver half-life. Sequential two-dimensional images of
      PCA distribution in a plane longitudinal to the rat body were obtained from eight
      spectra in the presence of a gradient of 12 mT/m (acquisition time 5 min; spatial
      resolution 8 mm). After 7 min, the nitroxide was detectable in the left side of
      the thorax area, but it was mostly localized in the liver. PCA was more uniformly
      distributed in the image collected after 17 min.

PMID- 7811943
TI  - Analysis of receptor clustering on cell surfaces by imaging fluorescent
      particles.
AB  - Fluorescently labeled low density lipoproteins (LDL) and influenza virus
      particles were bound to the surface of human fibroblasts and imaged with a cooled
      slow-scan CCD camera attached to a fluorescence microscope. Particles were also
      imaged after attachment to polylysine-coated microscope slides. The digital
      images were analyzed by fitting data points in the region of fluorescent spots by
      a two-dimensional Gaussian function, thus obtaining a measure of spot intensity
      with correction for local background. The intensity distributions for particles
      bound to polylysine slides were mainly accounted for by particle size
      distributions as determined by electron microscopy. In the case of LDL, the
      intensity distributions for particles bound to fibroblasts were considerably
      broadened, indicative of clustering. The on-cell intensity distributions were
      deconvolved into 1-particle, 2-particle, 3-particle, etc. components using the
      data obtained with LDL bound to polylysine-coated slides as an empirical measure
      of the single particle intensity distribution. This procedure yielded a
      reasonably accurate measure of the proportion of single particles, but large
      errors were encountered in the proportions of larger cluster sizes. The
      possibility of studying the dynamics of clustering was investigated by binding
      LDL to cells at 4 degrees C and observing changes in the intensity distribution
      with time after warming to 20 degrees C.

PMID- 7811944
TI  - Tracking of single fluorescent particles in three dimensions: use of cylindrical
      optics to encode particle position.
AB  - We present a novel optical technique for three-dimensional tracking of single
      fluorescent particles using a modified epifluorescence microscope containing a
      weak cylindrical lens in the detection optics and a microstepper-controlled fine
      focus. Images of small, fluorescent particles were circular in focus but
      ellipsoidal above and below focus; the major axis of the ellipsoid shifted by 90
      degrees in going through focus. Particle z position was determined from the image
      shape and orientation by applying a peak detection algorithm to image projections
      along the x and y axes; x, y position was determined from the centroid of the
      particle image. Typical spatial resolution was 12 nm along the optical axis and 5
      nm in the image plane with a maximum sampling rate of 3-4 Hz. The method was
      applied to track fluorescent particles in artificial solutions and living cells.
      In a solution of viscosity 30 cP, the mean squared distance (MSD) traveled by a
      264 nm diameter rhodamine-labeled bead was linear with time to 20 s. The measured
      diffusion coefficient, 0.0558 +/- 0.001 micron2/s (SE, n = 4), agreed with the
      theoretical value of 0.0556 micron2/s. Statistical variability of MSD curves for
      a freely diffusing bead was in quantitative agreement with Monte Carlo
      simulations of three-dimensional random walks. In a porous glass matrix, the MSD
      data was curvilinear and showed reduced bead diffusion. In cytoplasm of Swiss 3T3
      fibroblasts, bead diffusion was restricted. The water permeability in individual
      Chinese Hamster Ovary cells was measured from the z movement of a fluorescent
      bead fixed at the cell surface in response osmotic gradients; water permeability
      was increased by > threefold in cells expressing CHIP28 water channels. The
      simplicity and precision of this tracking method may be useful to quantify the
      complex trajectories of fluorescent particles in living cells.

PMID- 7811945
TI  - Multiple site optical recording of transmembrane voltage (MSORTV) in patterned
      growth heart cell cultures: assessing electrical behavior, with microsecond
      resolution, on a cellular and subcellular scale.
AB  - We have applied multiple site optical recording of transmembrane voltage (MSORTV)
      to patterned growth cultures of heart cells to analyze the effect of geometry per
      se on impulse propagation in excitable tissue, with cellular and subcellular
      resolution. Extensive dye screening led to the choice of di-8-ANEPPS as the most
      suitable voltage-sensitive dye for this application; it is internalized slowly
      and permits optical recording with signal-to-noise ratios as high as 40:1
      (measured peak-to-peak) and average fractional fluorescence changes of 15% per
      100 mV. Using a x 100 objective and a fast data acquisition system, we could
      resolve impulse propagation on a microscopic scale (15 microns) with high
      temporal resolution (uncertainty of +/- 5 microseconds). We could observe the
      decrease in conduction velocity of an impulse propagating along a narrow cell
      strand as it enters a region of abrupt expansion, and we could explain this
      phenomenon in terms of the micro-architecture of the tissue. In contrast with the
      elongated and aligned cells forming the narrow strands, the cells forming the
      expansions were aligned at random and presented 2.5 times as many cell-to-cell
      appositions per unit length. If the decrease in conduction velocity results
      entirely from this increased number of cell-to-cell boundaries per unit length,
      the mean activation delay introduced by each boundary can be estimated to be 70
      microseconds. Using this novel experimental system, we could also demonstrate the
      electrical coupling of fibroblasts and endotheloid cells to myocytes in culture.

PMID- 7811946
TI  - Influence of surface and protein modification on immunoglobulin G adsorption
      observed by scanning force microscopy.
AB  - Scanning force microscopy has been used successfully to produce images of
      individual protein molecules. However, one of the problems with this approach has
      been the high mobility of the proteins caused by the interaction between the
      sample and the scanning tip. To stabilize the proteins we have modified the
      adsorption properties of immunoglobulin G on graphite and mica surfaces. We have
      used two approaches: first, we applied glow discharge treatment to the surface to
      increase the hydrophilicity, favoring adhesion of hydrophilic protein molecules;
      second, we used the arginine modifying reagent phenylglyoxal to increase the
      protein hydrophobicity and thus enhance its adherence to hydrophobic surfaces. We
      used scanning force microscopy to show that the glow discharge treatment favors a
      more homogeneous distribution and stronger adherence of the protein molecules to
      the graphite surface. Chemical modification of the immunoglobulin caused
      increased aggregation of the proteins on the surface but did not improve the
      adherence to graphite. On mica, clusters of modified immunoglobulins were also
      observed and their adsorption was reduced. These results underline the importance
      of the surface hydrophobicity and charge in controlling the distribution of
      proteins on the surface.

PMID- 7811947
TI  - Reversible binding kinetics of a cytoskeletal protein at the erythrocyte
      submembrane.
AB  - Reversible binding among components of the cellular submembrane cytoskeleton and
      reversible binding of some of these components with the plasma membrane likely
      play a role in nonelastic morphological changes and mechanoplastic properties of
      cells. However, relatively few studies have been devoted to investigating
      directly the kinetic aspects of the interactions of individual components of the
      membrane skeleton with the membrane. The experiments described here investigated
      whether one component of the erythrocyte membrane cytoskeleton, protein 4.1,
      binds to its sites on the membrane reversibly and if so, whether the different
      4.1-binding sites display distinct kinetic behavior. Protein 4.1 is known to
      stabilize the membrane and to mediate the attachment of spectrin filaments to the
      membrane. Protein 4.1 previously has been shown to bind to integral membrane
      proteins band 3, glycophorin C, and to negatively charged phospholipids. To
      examine the kinetic rates of dissociation of carboxymethyl fluorescein-labeled
      4.1 (CF-4.1) to the cytofacial surface of erythrocyte membrane, a special
      preparation of hemolyzed erythrocyte ghosts was used, in which the ghosts became
      flattened on a glass surface and exposed their cytofacial surfaces to the
      solution through a membrane rip in a distinctive characteristic pattern. This
      preparation was examined by the microscopy technique of total internal
      reflection/fluorescence recovery after photobleaching (TIR/FRAP). Four different
      treatments were employed to help identify which membrane binding sites gave rise
      to the multiplicity of observed kinetic rates. The first treatment, the control,
      stripped off the native spectrin, actin, 4.1, and ankyrin. About 60% of the CF
      4.1 bound to this control binded irreversibly (dissociation time > 20 min), but
      the remaining approximately 40% binded reversibly with a range of residency times
      averaging approximately 3 s. The second treatment subjected these stripped
      membranes to trypsin, which presumably removed most of the band 3. CF-4.1 binded
      significantly less to these trypsinized membranes and most of the decrease was a
      loss of the irreversibly binding sites. The third treatment simply preserved the
      native 4.1 and ankyrin. CF-4.1 binded less to this sample too, and the loss
      involved both the irreversible and reversible sites. The fourth treatment blocked
      the gycophorin C sites on the native 4.1-stripped membranes with an antibody. CF
      4.1 again binded less to this sample than to a nonimmune serum control, and
      almost all of the decrease is a loss of irreversible sites. These rest suggest
      that 1) protein 4.1 binds to membrane or submembrane sites at least in part
      reversibly ; 2) the most reversible sites are probably not proteinaceous and not
      glycophorin C, but possibly are phospholipids (especially phosphatidylserine);
      and 3) TIWRFRAP can successfully examine the fast reversible dynamics of
      cytoskeletal components binding to biological membranes.

PMID- 7811950
TI  - When flies are flat and dead.

PMID- 7811948
TI  - Dynamic gap junctional communication: a delimiting model for tissue responses.
AB  - Gap junctions are aqueous intercellular channels formed by a diverse class of
      membrane-spanning proteins, known as connexins. These aqueous pores provide
      partial cytoplasmic continuity between cells in most tissues, and are freely
      permeable to a host of physiologically relevant second messenger molecules/ionic
      species (e.g., Ca2+, IP3, cAMP, cGMP). Despite the fact that these second
      messenger molecules/ionic species have been shown to alter junctional patency,
      there is no clear basis for understanding how dynamic and transient changes in
      the intracellular concentration of second messenger molecules might modulate the
      extent of intercellular communication among coupled cells. Thus, we have modified
      the tissue monolayer model of Ramanan and Brink (1990) to account for both the up
      regulatory and down-regulatory effects on junctions by second messenger molecules
      that diffuse through gap junctions. We have chosen the vascular wall as our
      morphological correlate because of its anisotropy and large investment of gap
      junctions. The model allows us to illustrate the putative behavior of gap
      junctions under a variety of physiologically relevant conditions. The modeling
      studies demonstrated that transient alterations in intracellular second messenger
      concentrations are capable of producing 50-125% changes in the number of cells
      recruited into a functional syncytial unit, after activation of a single cell.
      Moreover, the model conditions required to demonstrate such physiologically
      relevant changes in intercellular diffusion among coupled cells are commonly
      observed in intact tissues and cultured cells.

PMID- 7811949
TI  - A Monte Carlo study of the dynamics of G-protein activation.
AB  - To link quantitatively the cell surface binding of ligand to receptor with the
      production of cellular responses, it may be necessary to explore early events in
      signal transduction such as G-protein activation. Two different model frameworks
      relating receptor/ligand binding to G-protein activation are examined. In the
      first framework, a simple ordinary differential equation model is used to
      describe receptor/ligand binding and G-protein activation. In the second
      framework, the events leading to G-protein activation are simulated using a
      dynamic Monte Carlo model. In both models, reactions between ligand-bound
      receptors and G-proteins are assumed to be diffusion-limited. The Monte Carlo
      model predicts two regimes of G-protein activation, depending upon whether the
      lifetime of a receptor/ligand complex is long or short compared with the time
      needed for diffusional encounters of complexes and G-proteins. When the lifetime
      of a complex is relatively short compared with the diffusion time, the movement
      of ligand among free receptors by binding and unbinding ("switching")
      significantly enhances G-protein activation. Receptor antagonists dramatically
      reduce G-protein activation and, thus, signal transduction in this case, and
      significant clustering of active G-proteins near receptor/ligand complexes
      results. The simple ordinary differential equation model poorly predicts G
      protein activation for this situation. In the alternative case, when diffusion is
      relatively fast, ligand movement among receptors is less important and the simple
      ordinary differential equation model and Monte Carlo model results are similar.
      In this case, there is little clustering of active G-proteins near
      receptor/ligand complexes. Results also indicate that as the GTPase activity of
      the alpha-subunit decreases, the steady-state level of alpha-GTP increases,
      although temporal sensitivity is compromised.

PMID- 7811951
TI  - Lateral diffusion measurement at high spatial resolution by scanning
      microphotolysis in a confocal microscope.
AB  - Fluorescence photobleaching methods have been widely used to study diffusion
      processes in the plasma membrane of single living cells and other membrane
      systems. Here we describe the application of a new photobleaching technique,
      scanning microphotolysis. Employing a recently developed extension module to a
      commercial confocal microscope, an intensive laser beam was switched on and off
      during scanning according to a user definable image mask. Thereby the location,
      geometry, and number of photolysed spots could be chosen arbitrarily, their size
      ranging from tens of micrometers down to the diffraction limit. Therewith we
      bleached circular areas on the surface of single living 3T3 cells labeled with
      the fluorescent lipid analog NBD-HPC. Subsequently, the fluorescence recovery
      process was observed using the attenuated laser beam for excitation. This yielded
      image stacks representing snapshots of the spatial distribution of fluorescent
      molecules. From these we computed the radial distribution functions of the
      photobleached dye molecules. The variance of these distributions is linearly
      related to the diffusion constant, time, and the mobile fraction of the diffusing
      species. Furthermore, we compared directly the theoretically expected and
      measured distribution functions, and could thus determine the diffusion
      coefficient from each single image. The results of these two new evaluation
      methods (D = 0.3 +/- 0.1 micron 2/s) agreed well with the outcome of conventional
      fluorescence recovery measurements. We show that by scanning microphotolysis
      information on dynamical processes such as diffusion of lipids or proteins can be
      acquired at the superior spatial resolution of a confocal laser scanning
      microscope.

PMID- 7811952
TI  - Time-resolved delayed luminescence image microscopy using an europium ion chelate
      complex.
AB  - Improvements and extended applications of time-resolved delayed luminescence
      imaging microscopy (TR-DLIM) in cell biology are described. The emission
      properties of europium ion complexed to a fluorescent chelating group capable of
      labeling proteins are exploited to provide high contrast images of biotin labeled
      ligands through detection of the delayed emission. The streptavidin-based
      macromolecular complex (SBMC) employs streptavidin cross-linked to thyroglobulin
      multiply labeled with the europium-fluorescent chelate. The fluorescent chelate
      is efficiently excited with 340-nm light, after which it sensitizes europium ion
      emission at 612 nm hundreds of microseconds later. The SBMC complex has a high
      quantum yield orders of magnitude higher than that of eosin, a commonly used
      delayed luminescent probe, and can be readily seen by the naked eye, even in
      specimens double-labeled with prompt fluorescent probes. Unlike triplet-state
      phosphorescent probes, sensitized europium ion emission is insensitive to
      photobleaching and quenching by molecular oxygen; these properties have been
      exploited to obtain delayed luminescence images of living cells in aerated medium
      thus complementing imaging studies using prompt fluorescent probes. Since TR-DLIM
      has the unique property of rejecting enormous signals that originate from
      scattered light, autofluorescence, and prompt fluorescence it has been possible
      to resolve double emission images of living amoeba cells containing an intensely
      stained lucifer yellow in pinocytosed vesicles and membrane surface-bound SBMC
      labeled biotinylated concanavalin A. Images of fixed cells represented in terms
      of the time decay of the sensitized emission show the lifetime of the europium
      ion emission is sensitive to the environment in which it is found. Through the
      coupling of SBMC to streptavidin,a plethora of biotin-based tracer molecules are
      available for immunocytochemical studies.

PMID- 7811953
TI  - Diffusion cannot govern the discharge of neurotransmitter in fast synapses.
AB  - In the present work we show that diffusion cannot provide the observed fast
      discharge of neurotransmitter from a synaptic vesicle during neurotransmitter
      release, mainly because it is not sufficiently rapid nor is it sufficiently
      temperature-dependent. Modeling the discharge from the vesicle into the cleft as
      a continuous point source, we have determined that discharge should occur in 50
      75 microseconds, to provide the observed high concentrations of transmitter at
      the critical zone.

PMID- 7811954
TI  - Actin-crosslinking protein regulation of filament movement in motility assays: a
      theoretical model.
AB  - The interaction of single actin filaments on a myosin-coated coverslip has been
      modeled by several authors. One model adds a component of "frictional drag" by
      myosin heads that oppose movement of the actin filaments. We have extended this
      concept by including the resistive drag from actin crosslinking proteins to
      understand better the relationship among crosslinking number, actin-myosin force
      generation, and motility. The validity of this model is supported by agreement
      with the experimental results from a previous study in which crosslinking
      proteins were added with myosin molecules under otherwise standard motility assay
      conditions. The theoretical relationship provides a means to determine many
      physical parameters that characterize the interaction between a single actin
      filament and a single actin-crosslinking molecule (various types). In particular,
      the force constant of a single filamin molecule is calculated as 1.105 pN,
      approximately 3 times less than a driving myosin head (3.4 pN). Knowledge of this
      parameter and others derived from this model allows a better understanding of the
      interaction between myosin and the actin/actin-binding protein cytoskeleton and
      the role of actin-binding proteins in the regulation and modulation of motility.

PMID- 7811955
TI  - Mean-field calculations of chain packing and conformational statistics in lipid
      bilayers: comparison with experiments and molecular dynamics studies.
AB  - A molecular, mean-field theory of chain packing statistics in aggregates of
      amphiphilic molecules is applied to calculate the conformational properties of
      the lipid chains comprising the hydrophobic cores of dipalmitoyl
      phosphatidylcholine (DPPC), dioleoyl-phosphatidylcholine (DOPC), and palmitoyl
      oleoyl-phosphatidylcholine (POPC) bilayers in their fluid state. The central
      quantity in this theory, the probability distribution of chain conformations, is
      evaluated by minimizing the free energy of the bilayer assuming only that the
      segment density within the hydrophobic region is uniform (liquidlike). Using this
      distribution we calculate chain conformational properties such as bond
      orientational order parameters and spatial distributions of the various chain
      segments. The lipid chains, both the saturated palmitoyl (-(CH2)14-CH3) and the
      unsaturated oleoyl (-(CH2)7-CH = CH-(CH2)7-CH3) chains are modeled using
      rotational isomeric state schemes. All possible chain conformations are
      enumerated and their statistical weights are determined by the self-consistency
      equations expressing the condition of uniform density. The hydrophobic core of
      the DPPC bilayer is treated as composed of single (palmitoyl) chain amphiphiles,
      i.e., the interactions between chains originating from the same lipid headgroup
      are assumed to be the same as those between chains belonging to different
      molecules. Similarly, the DOPC system is treated as a bilayer of oleoyl chains.
      The POPC bilayer is modeled as an equimolar mixture of palmitoyl and oleoyl
      chains. Bond orientational order parameter profiles, and segment spatial
      distributions are calculated for the three systems above, for several values of
      the bilayer thickness (or, equivalently, average area/headgroup) chosen, where
      possible, so as to allow for comparisons with available experimental data and/or
      molecular dynamics simulations. In most cases the agreement between the mean
      field calculations, which are relatively easy to perform, and the experimental
      and simulation data is very good, supporting their use as an efficient tool for
      analyzing a variety of systems subject to varying conditions (e.g., bilayers of
      different compositions or thicknesses at different temperatures).

PMID- 7811957
TI  - Monte Carlo simulation of ligand-receptor interactions on a cell surface.
AB  - In this paper we develop a compartmentalized, discrete simulation model for
      investigating the spatial distribution and dynamic properties of receptor
      crosslinking on the surface of a cell. Results generated by the model are
      compared with some of the major results of existing analytical models, and
      differences are discussed in relation to differences in the model assumptions.
      Finally, the model is used to evaluate the dynamic effects of a time-varying non
      homogeneous ligand concentration.

PMID- 7811958
TI  - Molecular neural network devices based on non-linear dynamic media.
AB  - The importance of non-linear dynamic mechanisms for implementing neural network
      devices at a molecular level is discussed. Information processing devices based
      on these mechanisms proved to be capable of performing some primitive operations
      important for image processing.

PMID- 7811956
TI  - Transport properties of single-file pores with two conformational states.
AB  - Complex facilitative membrane transporters of specific ligands may operate via
      inner channels subject to conformational transitions. To describe some properties
      of these systems, we introduce here a kinetic model of coupled transport of two
      species, L and w, through a two-conformational pore. The basic assumptions of the
      model are: a) single-file of, at most, n molecules inside the channel; b) each
      pore state is open to one of the compartments only; c) there is at most only one
      vacancy per pore; d) inside the channel, a molecule of L occupies the same
      positions as a molecule of w; and e) there is at most only one molecule of L per
      pore. We develop a general representation of the kinetic diagram of the model
      that is formally similar to the one used to describe one-vacancy transport
      through a one-conformational single-file pore. In many cases of biological
      importance, L could be a hydrophilic (ionic or nonionic) ligand and w could be
      water. The model also finds application to describe solute (w) transport under
      saturation conditions. In this latter case, L would be another solute, or a
      tracer of w. We derive steady-state expressions for the fluxes of L and w, and
      for the permeability coefficients. The main results obtained from the analysis of
      the model are the following. 1) Under the condition of equilibrium of w, the
      expression derived for the flux of L is formally indistinguishable from the one
      obtainable from a standard four-state model of ligand transport mediated by a two
      conformational transporter. 2) When L is a tracer of w, we can derive an
      expression for the ratio between the main isotope and tracer permeability
      coefficients (Pw/Pd). We find that the near-equilibrium permeability ratio
      satisfies (n - 1) < or = (Pw/Pd)eq < or = n, a result previously derived for the
      one-conformational, single-file pore for the case that n > or = 2. 3) The kinetic
      model studied here represents a generalization of the carrier concept. In fact,
      for the case that n = 1 (corresponding to the classical single-occupancy
      carrier), the near-equilibrium permeability ratio satisfies 0 < or = (Pw/Pd)eq <
      or = 1, which is characteristic of a carrier performing exchange-diffusion.

PMID- 7811959
TI  - The informational context of the third base in amino acid codons.
AB  - It is shown that in the pairs of amino acids coded by the codons possesing
      identical bases in the first and second positions, the amino acids with R in the
      third position are of higher structural importance (which is reflected by higher
      values of (P alpha + P beta) sums of Chou-Fasman conformational parameters), and
      of stronger helix forming potentials (reflected by the differences (P alpha - P
      beta)), than the amino acids coded with Y. The same structural factors seem to be
      of importance for the codon choice in the case of amino acids coded by more than
      two codons. The amino acids which prefer alpha-helical over the beta-sheet
      conformation favour the codons with R in their third position, and those which
      favour the beta-sheet conformation favour the codons with Y in this position.

PMID- 7811960
TI  - Cell movement and shape are non-random and determined by intracellular,
      oscillatory rotating waves in Dictyostelium amoebae.
AB  - We present evidence for a mechanism of eukaryotic cell movement. The pseudopodial
      dynamics and shape of Dictyostelium discoideum amoebae were investigated using
      computer-supported video microscopy. An examination of the cell periphery by the
      novel method of serial circular maps revealed explicit, classical wave patterns,
      which indicate the existence of intrinsic intracellular oscillations. The
      patterns are generated by the transit of self-organized, super-positioned,
      harmonic modes of rotating oscillatory waves (ROWS). These waves are probably
      associated with the dynamics of intracellular actin polymerisation and
      depolymerisation. A Karhunen-Loeve expansion was conducted on one cell during 10
      min of locomotion using points each 10 degrees around the cell's boundary. The
      results show that only 2-3 modes are necessary to describe the most essential
      features of cell movement and shape. Based on this analysis, a wave model was
      developed, which accurately simulates the dynamics of cell movement and shape
      during this time. The model was tested by reconstructing the cell's dynamical
      form by means of the Karhunen-Loeve transform. No difference was detected between
      this reconstruction and the actual cell outline. Although cell movement and shape
      have hitherto been viewed as random, our results demonstrate that ROWS determine
      the spatio-temporal expression of pseudopodia, and consequently govern cell shape
      and movement, non-randomly.

PMID- 7811961
TI  - A transfer-function representation for the input-output relation in consecutive
      Michaelis-Menten-type reactions.
AB  - A transfer-function representation is devised to describe analytically and
      approximately the reaction velocity (output) in response to the substrate influx
      rate (input) in single and two consecutive Michaelis-Menten-type reactions in an
      open and homogeneous system. The transfer function for single reactions has an
      expression of first-order system, the time constant of which is dependent on the
      kinetic parameters and flow rate (steady-state value of the input and output),
      but independent of the magnitude of the input change. The transfer function for
      the two-reaction system can be formed with successive multiplication of the
      transfer functions for the first and second reactions. The validity of the
      representation is examined with variation in the kinetic parameters and flow rate
      by comparing the output of the transfer function with the actual response
      obtained from the computer simulation, that is, numerical integration of the rate
      equation. The analysis of the indicial responses indicates that the transfer
      functions for single and two consecutive reactions are valid within a certain
      error for the response around a steady state.

PMID- 7811962
TI  - Expression of engineered antibodies in plant cells.

PMID- 7811963
TI  - Hsp70 heat shock protein cognate is expressed and stored in developing tomato
      pollen.
AB  - Pollen of angiosperms lacks the ability to respond to heat stress by synthesizing
      heat shock proteins (hsps). In tomato developing microspores were found to have
      70 kDa heat shock proteins (hsp70s) present throughout development, even in the
      absence of heat stress. Heat shock protein family members expressed in the
      absence of heat stress are called cognate (hsc70) genes. Antisense RNA and
      antibody probes were used for in situ hybridizations which detected hsc70
      expression in developing pollen of immature buds. Hsc70 mRNA transcripts and
      proteins were detected in nonstressed sporogenous tissues, microspores and in pre
      tapetal layers during early pollen development. While immunoblot analysis
      detected hsc70 proteins stored in mature pollen, heat stress could not induce the
      synthesis of new hsp70 protein as measured by 35S-methionine labeling followed by
      immunoprecipitation.

PMID- 7811964
TI  - Molecular characterization of the DNA-binding and dimerization domains of the
      bZIP transcription factor, EmBP-1.
AB  - The wheat basic-leucine zipper (bZIP) DNA-binding protein EmBP-1 has been
      implicated in the mechanisms of abscisic acid (ABA) mediated gene regulation.
      Sequence and structural homology to the yeast bZIP protein GCN4 has been used to
      predict the location of the functional domains of EmBP-1. In order to test these
      predictions, the presumptive DNA-binding and dimerization domains of EmBP-1 were
      mapped by producing a series of truncated protein fragments and functionally
      testing them in vitro. Deletion of 5 amino acids of the predicted basic domain
      resulted in a loss of all DNA-binding activity. A fragment containing all six
      leucine repeat elements showed strong DNA-binding activity. Sequential deletion
      of the leucine repeat elements resulted in first an increase in DNA-binding
      activity (-L6 and -L5) followed by a reduction in binding activity (-L4) and
      eventually complete elimination of all detectable DNA-binding activity (-L3 and 
      L2). This demonstrates the importance of an intact leucine zipper domain of at
      least 4 repeat elements for efficient DNA-binding. The smallest polypeptide that
      retained DNA-binding activity is a fragment spanning amino acid residues 248-308
      (ca. 8.4 kDa) consisting of minimal basic and leucine zipper domains.
      Dimerization of EmBP-1 was demonstrated by co-translation of fragments of
      differing molecular weights and identification of a DNA-protein complex with
      intermediate mobility to that produced by each fragment alone. A unique leucine
      proline repeat element found N-terminal to the DNA-binding domain of EmBP-1 does
      not appear to play a role in DNA-binding or dimerization. These results confirm
      the locations of the functional domains of EmBP-1 predicted by similarity to
      GCN4. The high degree of functional conservation of the bZIP proteins spanning
      organisms from plants to fungi highlights the ancient origin of this class of
      transcription factors and of the mechanisms of gene regulation in which they
      participate.

PMID- 7811965
TI  - The ocs element in the soybean GH2/4 promoter is activated by both active and
      inactive auxin and salicylic acid analogues.
AB  - The octopine synthase (ocs or ocs-like) element has been previously reported to
      be responsive to the plant hormones, auxin, salicylic acid, and methyl jasmonate.
      Using transient assays with carrot protoplasts, we have demonstrated that an ocs
      element from the soybean auxin-inducible GH2/4 promoter is not only activated by
      strong auxins (i.e., 2,4-dichlorophenoxyacetic acid, 2,4,5-trichlorophenoxyacetic
      acid, alpha-naphthalene acetic acid) and salicylic acid, but also by weak auxin
      analogues (beta-naphthalene acetic acid), inactive auxin analogs (i.e., 2,3
      dichlorophenoxyacetic acid, 2,4,6-trichlorophenoxyacetic acid), and inactive
      salicylic acid analogs (3-hydroxybenzoic acid and 4-hydroxybenzoic acid). Our
      results indicate that the ocs element in the GH2/4 promoter is not selectively
      induced by plant hormones and might function similarly to tandem AP-1 sites in
      some animal glutathione S-transferase (GST) genes. The ocs element, like the AP-1
      sites in animal GST promoters, may be induced not only by certain hormones but
      also by some non-hormonal stress-inducing or electrophilic agents.

PMID- 7811966
TI  - A method for examining expression of homologous genes in plant polyploids.
AB  - One of the essential issues regarding evolution of polyploid species is how
      duplicate genes are expressed. Most studies on gene expression in polyploids have
      been based on isozyme analyses; RNA analysis has not been widely used partially
      due to difficulties in distinguishing homologous transcripts which usually have
      the same length and similar or almost identical sequences. In this study, a
      method combining RT-PCR with RFLP was used to analyze transcripts of homologous
      genes in natural and synthetic Brassica amphidiploids. Sequences coding for
      several known genes were selected and used to synthesize gene-specific primers.
      Total RNAs were used as templates for RT-PCR to amplify homologous transcripts in
      three diploid parental species, three cultivated amphidiploid species and six
      synthetic amphidiploids. For each gene, initial PCR products amplified in all
      species had identical length; however, homologous transcripts in the diploid and
      amphidiploid species could be distinguished after digesting the PCR products with
      restriction enzymes. Preliminary results based on three genes indicated that both
      transcripts from the diploid parents were expressed in the synthetic and natural
      amphidiploids. This study represents the first application of RT-PCR and RFLP
      analysis to investigate expression of homologous genes in higher plants. The
      technique is a sensitive, simple and efficient method for distinguishing
      homologous transcripts in a mixed RNA population and can be applied to many types
      of studies on expression of homologous genes.

PMID- 7811967
TI  - Structure of the tomato Adh2 gene and Adh2 pseudogenes, and a study of Adh2 gene
      expression in fruit.
AB  - A cDNA library was constructed from RNA from the pericarp of ripe tomato fruit
      and four cDNAs encoding ADH2 were isolated and characterized. The cDNAs encode a
      peptide 379 amino acids in length. They hybridized strongly with a 1.8 kb RNA
      species well represented in RNA from ripe, but not from mature, unripe fruit, and
      strongly to a similar RNA species present in hypoxic, but not in aerobic roots.
      Northern analysis showed that the mRNA for ADH2 in fruit increased in abundance
      through ripening, particularly during late ripening. In pericarp tissue of fruit,
      the Adh2 mRNA level increased to a maximum within 8-16 h of exposure to
      atmospheres with 3% (v/v) oxygen, and returned to the basal level within 16 h of
      a return to air. The mRNA level was sensitive to the oxygen level in the
      atmosphere, increasing 20-fold in 12% (v/v) oxygen and 100-fold in 3% oxygen. The
      homologous tomato Adh2 gene was isolated from a genomic library. The gene has an
      overall length of 2334 bp from transcription start site to poly(A) addition site
      and includes eight introns. Southern blot analysis of tomato genomic DNA
      identified multiple Adh2-related sequences. Two of these, PSA1 and PSA2, were
      cloned and found to have 94% similarity with each other and 77% similarity with
      the tomato Adh2 gene over a 1000 bp region. The homologous regions include
      introns and exons but the equivalent exons contain frame shifts, deletions and
      stop codons. The two regions are therefore presumptive pseudogenes.

PMID- 7811968
TI  - Partial sequencing and mapping of clones from two maize cDNA libraries.
AB  - As one component of a maize genome project, we report the analysis of a number of
      randomly selected cDNAs, by a combination of measuring mRNA expression, 'single
      pass' sequencing (SPS), and genome mapping. Etiolated seedling (490) and membrane
      free polysomal endosperm cDNA clones (576) were evaluated for their transcription
      levels by hybridizing with a probe prepared from total mRNA and categorized as
      corresponding to abundantly or rarely expressed mRNAs and as either constitutive
      or tissue-specific. A total 313 clones from the two libraries were submitted to
      'single-pass' sequencing from the presumed 5' end of the mRNA and the nucleotide
      sequence compared with the GenBank database. About 61% of the clones showed no
      significant similarities within GenBank, 14% of the clones exhibited a high
      degree of similarity, while the remaining 25% exhibited a lesser degree of
      similarity. The chromosomal location of more than 300 clones was determined by
      RFLP mapping using standard populations. The results demonstrate that a
      combination of analyses provides synergistic information in eventually deducing
      the actual function of these types of clones.

PMID- 7811969
TI  - Evolutionary relationships among proteins in the phytohemagglutinin-arcelin-alpha
      amylase inhibitor family of the common bean and its relatives.
AB  - The common bean, Phaseolus vulgaris, contains a family of defense proteins that
      comprises phytohemagglutinin (PHA), arcelin, and alpha-amylase inhibitor (alpha
      AI). Here we report eight new derived amino acid sequences of genes in this
      family obtained with either the polymerase chain reaction using genomic DNA, or
      by screening cDNA libraries made with RNA from developing beans. These new
      sequences are: two alpha AI sequences and arcelin-4 obtained from a wild
      accession of P. vulgaris that is resistant to the Mexican bean weevil (Zabrotes
      subfasciatus) and the bean weevil (Acanthoscelides obtectus); an alpha AI
      sequence from the related species P. acutifolius (tepary bean); a PHA and an
      arcelin-like sequence from P. acutifolius; an alpha AI-like sequence from P.
      maculatus; and a PHA sequence from an arcelin-5 type P. vulgaris. A dendrogram of
      16 sequences shows that they fall into the three identified groups:
      phytohemagglutinins, arcelins and alpha AIs. A comparison of these derived amino
      acid sequences indicates that one of the four amino acid residues that is
      conserved in all legume lectins and is required for carbohydrate binding is
      absent from all the arcelins; two of the four conserved residues needed for
      carbohydrate binding are missing from all the alpha AIs. Proteolytic processing
      at an Asn-Ser site is required for the activation of alpha AI, and this site is
      present in all alpha AI-like sequences; this processing site is also found at the
      same position in certain arcelins, which are not proteolytically processed. The
      presence of this site is therefore not sufficient for processing to occur.

PMID- 7811970
TI  - Effects of an antisense napin gene on seed storage compounds in transgenic
      Brassica napus seeds.
AB  - To manipulate the quantity and quality of storage components in Brassica napus
      seeds, we have constructed an antisense gene for the storage protein napin. The
      antisense gene was driven by the 5'-flanking region of the B. napus napin gene to
      express antisense RNA in a seed-specific manner. Seeds of transgenic plants with
      antisense genes often contained reduced amounts of napin. In some transgenic
      plants, no accumulation of napin was observed. However, the total protein content
      of transgenic and wild-type seeds did not differ significantly. Seeds lacking
      napin accumulated 1.4 to 1.5 times more cruciferin than untransformed seeds,
      although the oleosin content was not affected. Fatty acid content and composition
      in the seeds of transgenic plants were also analyzed by gas chromatography.
      Though the total fatty acid content of the transformants was the same as that of
      non-transformants, there was a reduction in 18:1 contents and a concomitant
      increase of 18:2 in seeds with reduced napin levels. This observed change in
      fatty acid composition was inherited in the next generation.

PMID- 7811971
TI  - Characterisation of cDNA and genomic clones encoding homologues of the 65 kDa
      regulatory subunit of protein phosphatase 2A in Arabidopsis thaliana.
AB  - Two cDNA species encoding sequences homologous to the 65 kDa regulatory subunit
      (PR 65) of protein phosphatase 2A (PP2A) have been isolated from an Arabidopsis
      thaliana cDNA library. These were designated pDF1 and pDF2. pDF1 is 1795 bp long
      and by comparison with the human and porcine PP2A regulatory subunit sequences
      represents a full-length clone. It encodes a predicted polypeptide of 587 amino
      acid residues. pDF2 is truncated at the 5' end by 237 bp. The complete nucleotide
      sequences have been determined for both cDNA species. Comparison of the
      nucleotide and the deduced amino acid sequences showed that the two sequences
      were homologous but not identical and therefore must be derived from two
      different genes. Northern blot analysis was performed on total RNA and poly(A)+
      RNA isolated from seed at various stages of development and from young leaf
      material of Brassica napus L. (oilseed rape). Both cDNA probes hybridised to a
      single major mRNA species of ca. 2.2 kb. The highest level of expression was
      observed in the total RNA from developing rape seed at about 33 days after
      flowering, and the transcript level in the poly(A)+ RNA of the seed was higher
      than in young leaf of oilseed rape. Southern blot analysis was performed on two
      varieties of A. thaliana and B. napus genomic DNA; this identified a small family
      of genes in A. thaliana consisting of at least 2 or 3 members and a larger
      multigene family in B. napus of at least 5 or 6 members. Two independent genomic
      clones were isolated from an A. thaliana genomic library. Sequencing of a
      fragment common to both revealed that the sequence was identical in both clones
      and, therefore, they were assumed to contain the same genomic sequence. The
      genomic sequence selected, designated regA, is 3639 bp long and the coding
      sequence contains eleven introns. The gene encodes a predicted polypeptide of 590
      amino acid residues. The sequence comparison with both cDNA sequences showed that
      it is homologous but not identical to the two, confirming that at least three
      different genes exist in A. thaliana which encode PR65 of PP2A.

PMID- 7811972
TI  - Molecular analysis of the myosin gene family in Arabidopsis thaliana.
AB  - Myosin is believed to act as the molecular motor for many actin-based motility
      processes in eukaryotes. It is becoming apparent that a single species may
      possess multiple myosin isoforms, and at least seven distinct classes of myosin
      have been identified from studies of animals, fungi, and protozoans. The
      complexity of the myosin heavy-chain gene family in higher plants was
      investigated by isolating and characterizing myosin genomic and cDNA clones from
      Arabidopsis thaliana. Six myosin-like genes were identified from three polymerase
      chain reaction (PCR) products (PCR1, PCR11, PCR43) and three cDNA clones (ATM2,
      MYA2, MYA3). Sequence comparisons of the deduced head domains suggest that these
      myosins are members of two major classes. Analysis of the overall structure of
      the ATM2 and MYA2 myosins shows that they are similar to the previously
      identified ATM1 and MYA1 myosins, respectively. The MYA3 appears to possess a
      novel tail domain, with five IQ repeats, a six-member imperfect repeat, and a
      segment of unique sequence. Northern blot analyses indicate that some of the
      Arabidopsis myosin genes are preferentially expressed in different plant organs.
      Combined with previous studies, these results show that the Arabidopsis genome
      contains at least eight myosin-like genes representing two distinct classes.

PMID- 7811973
TI  - Molecular characterization of a novel, nuclear-encoded, NAD(+)-dependent
      glyceraldehyde-3-phosphate dehydrogenase in plastids of the gymnosperm Pinus
      sylvestris L.
AB  - Angiosperms and algae possess two distinct glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH) enzymes, an NAD(+)-dependent tetramer involved in cytosolic
      glycolysis and an NADP(+)-dependent enzyme of the Calvin cycle in chloroplasts.
      We have found that the gymnosperm Pinus sylvestris possesses, in addition to
      these, a nuclear-encoded, plastid-specific, NAD(+)-dependent GAPDH, designated
      GapCp, which has not previously been described from any plant. Several
      independent full-size cDNAs for this enzyme were isolated which encode a
      functional transit peptide and mature subunit very similar to that of cytosolic
      GAPDH of angiosperms and algae. A molecular phylogeny reveals that chloroplast
      GapCp and cytosolic GapC arose through gene duplication early in chlorophyte
      evolution. The GapCp gene is expressed as highly as that for GapC in light-grown
      pine seedlings. These findings suggest that aspects of compartmentalized sugar
      phosphate metabolism may differ in angiosperms and gymnosperms and furthermore
      underscore the contributions of endosymbiotic gene transfer and gene duplication
      to the nuclear complement of genes for enzymes of plant primary metabolism.

PMID- 7811974
TI  - Pattern and degree of methylation in ribosomal RNA genes of Cucurbita pepo L.
AB  - Methylation with respect to its degree and distribution throughout the 18S, 5.8S
      and 25S rRNA gene clusters (rDNA) and within single rDNA repeats in seedlings of
      the higher plant Cucurbita pepo L. (zucchini) was investigated. In this plant,
      which is characterized by several thousand repeats, at least 70% are completely
      or nearly completely methylated in CpGs and to a lower degree in CpNpGs. Detailed
      methylation analysis revealed that a fraction of about 3-4% of all repeats is
      hypomethylated near the transcription initiation site (TIS) which may indicate
      the fraction of active repeats in C. pepo. However, a different fraction (3-4% of
      all repeats) which is not methylated in all sites tested (including those at the
      TIS) is present in C. pepo and may thus represent active but differentially
      methylated rDNA. The results are discussed in context of recent models on
      methylation and gene activity.

PMID- 7811975
TI  - Bean cyclophilin gene expression during plant development and stress conditions.
AB  - Cyclophilins (Cyp) are ubiquitous proteins with peptidyl-prolyl cis-trans
      isomerase activity that catalyses rotation of X-Pro peptide bonds and facilitates
      the folding of proteins; these enzymes are believed to play a role in in vivo
      protein folding. During development of normal bean plants, Cyp transcripts are
      first detected three days after beginning of germination and are present in all
      plant tissues examined. In a general way, higher amounts of Cyp mRNAs are found
      in developing tissues. Cyp mRNA accumulates in alfalfa mosaic virus-infected bean
      leaves and after ethephon and salicylic acid treatments. In response to a
      localized chemical treatment Cyp mRNA accumulation is observed in the untreated
      parts of the plants; however these changes in mRNA levels are restricted to the
      aerial part of the plant. A comparative study of Cyp mRNA accumulation in bean
      and maize in response to various external stimuli shows striking differences in
      profiles between the two plants. For instance, in response to heat shock, maize
      Cyp mRNA significantly accumulates, whereas no remaining mRNA is observed a few
      hours after the beginning of the heat stress in bean. Differences in mRNA
      accumulation profiles are also observed upon salt stress which induces the
      response earlier in maize than in bean, whereas the opposite situation is
      observed when plants are cold-stressed. All these findings further suggest that
      cyclophilin might be a stress-related protein.

PMID- 7811976
TI  - Molecular cloning of the Arabidopsis thaliana sedoheptulose-1,7-biphosphatase
      gene and expression studies in wheat and Arabidopsis thaliana.
AB  - We report here the isolation and nucleotide sequence of genomic clones encoding
      the chloroplast enzyme sedoheptulose-1,7-bisphosphatase (SBPase) from Arabidopsis
      thaliana. The coding region of this gene contains eight exons (72-76 bp) and
      seven introns (75-91 bp) and encodes a polypeptide of 393 amino acids. Unusually,
      the 5' non-coding region contains two additional AUG codons upstream of the
      translation initiation codon. A comparison of the deduced Arabidopsis and wheat
      SBPase polypeptide sequences reveals 78.6%, identity. Expression studies showed
      that the level of SBPase mRNA in Arabidopsis and wheat is regulated in a light
      dependent manner and is also influenced by the developmental stage of the leaf.
      Although the Arabidopsis SBPase gene is present in a single copy, two hybridizing
      transcripts were detected in some tissues, suggesting the presence of alternate
      transcription start sites in the upstream region.

PMID- 7811977
TI  - Cloning and expression of a cDNA encoding a cytoplasmic L5 ribosomal protein from
      alfalfa (Medicago sativa L.).
AB  - A cDNA encoding a putative cytoplasmic ribosomal protein L5 from alfalfa (MsRL5),
      the first sequence from higher plants, has been characterized. The derived amino
      acid sequence of 181 residues contains the L5 signature, is 72.2% identical to
      yeast ribosomal L5 and shares high identity with other RL5 peptides from
      eukaryotic origin. The sequence does not contain any signal or transit peptide
      and therefore might be cytoplasmic. In all alfalfa organs examined MsRL5
      transcripts were detected at approximately equal levels.

PMID- 7811979
TI  - Lipid transfer protein genes of loblolly pine are members of a complex gene
      family.
AB  - A loblolly pine (Pinus taeda L.) cDNA with properties of a nonspecific lipid
      transfer protein (nsltp) is reported. In contrast to simple family structures
      reported for a variety of angiosperm nsltp genes, the putative pine nsltp gene is
      a member of a complex family.

PMID- 7811978
TI  - PCR cloning and expression analysis of cDNAs encoding cysteine proteinases from
      germinating seeds of Vicia sativa L.
AB  - cDNA clones encoding cysteine proteinases from cotyledons of germinated seeds of
      Vicia sativa L. have been obtained by means of PCR. Degenerate oligonucleotide
      primers were designed according to conserved amino acid regions of known cysteine
      proteinases. The deduced amino acid sequences of the cDNA clones encoding
      VSCYSPR1 and VSCYSPR2 display strong homology to cysteine proteinases of the so
      called papain superfamily. Northern analyses revealed developmentally regulated
      expression of both the mRNAs in germinating seeds. The transcripts were shown to
      be products of two distinct single genes, each exhibiting structural
      polymorphisms as exposed in few nucleotide substitutions.

PMID- 7811980
TI  - Molecular analysis of two Brassica napus genes expressed in the stigma.
AB  - A partial cDNA clone, Pis 63, corresponding to a mRNA highly expressed in
      Brassica napus pistils, was isolated by differential screening. PCR was used to
      complete the Pis 63 sequence (Pis 63-1) and to obtain the sequence of another
      related cDNA (Pis 63-2). Northern blot and in situ analyses demonstrated that
      these transcripts are expressed in the stigma throughout flower development. Pis
      63-1 and Pis 63-2 display similarity to a cotton fibre cDNA clone.

PMID- 7811981
TI  - Import of the barley PSI-F subunit into the thylakoid lumen of isolated
      chloroplasts.
AB  - A full-length cDNA clone encoding the PSI-F subunit of barley photosystem I has
      been isolated and sequenced. The open reading frame encodes a precursor
      polypeptide with a deduced molecular mass of 24837 Da. The barley PSI-F precursor
      contains a bipartite presequence with characteristics similar to the presequences
      of proteins destined to the thylakoid lumen. In vitro import studies demonstrate
      that an in vitro synthesized precursor is transported across the chloroplast
      envelope and directed to the thylakoid membrane, where it accumulates in a
      protease-resistant form. Incubation of the precursor with a chloroplast stromal
      extract results in processing to a form intermediate in size between the
      precursor and mature forms. Hydrophobicity analysis of the barley PSI-F protein
      reveals a hydrophobic region predicted to be a membrane spanning alpha-helix. The
      hydrophobic nature of PSI-F combined with a bipartite presequence is unusual. We
      postulate that the second domain in the bipartite presequence of the PSI-F
      precursor proteins is required to ensure the proper orientation of PSI-F in the
      thylakoid membrane. The expression of the PsaF gene is light-induced similar to
      other barley photosystem I genes.

PMID- 7811982
TI  - Sharp divergence between wheat and barley at loci encoding novel members of the
      trypsin/alpha-amylase inhibitors family.
AB  - Amino acid sequences for three members (CMx1, CMx2, and CMx3) of a new subfamily
      of trypsin/alpha-amylase inhibitors in wheat have been deduced from the
      nucleotide sequences of the corresponding cDNAs. A cDNA clone encoding CMx1 was
      selected from a wheat developing endosperm library using a probe that encoded
      barley trypsin inhibitor BTI-CMe at low stringency. Sequences corresponding to
      CMx2 and CMx3 were obtained from cDNA amplified by the polymerase chain reaction.
      The three CMx sequences contain a premature stop codon after 363 nt, as well as a
      second stop codon at the same position as in BTI-CMe (nt 439-441). Southern
      analysis of DNAs from diploid, tetraploid, and hexaploid wheats, as well as from
      aneuploid lines, indicate that there is a single CMx locus in each of the three
      genomes of hexaploid wheat, respectively associated with chromosomal arms 4AS,
      4BS, and 4DL. These genes are expressed early during endosperm development and
      not expressed at detectable levels in other tissues. Evolutionary implications
      are discussed.

PMID- 7811983
TI  - Hospital care grievances and psychosocial needs expressed by PWAs: an analysis of
      qualitative data.
AB  - Despite the growing number of HIV-related hospital admissions, reports of
      hospitalization experiences of persons with AIDS has been sparse. As part of a
      larger quantitative study to assess how arrangements of care of patients with
      AIDS are related to quality of care, the authors analyzed qualitative data
      collected during interviews with 50 patients hospitalized for HIV-related
      complications. The responses are suggestive of problematic hospital care issues
      and indicate psychosocial concerns. Overarching themes emerged of communication
      deficits and depersonalizing behavior. This research can help healthcare
      professionals develop increased sensitivity to patients' perspectives of their
      circumstances. More extensive research is needed to evaluate and improve the
      experiences of patients during hospitalization for HIV-related illness.

PMID- 7811984
TI  - The content of ethical problems experienced by persons with AIDS.
AB  - The purpose of this research was to describe and examine the basic nature
      (essences) and content (subject-matter) of ethical problems involving AIDS that
      are experienced by persons with AIDS (PWAs). The participants were 25 PWAs and 5
      significant others, the latter included to provide contextual understanding.
      During audiotaped interviews, the PWAs described 45 different ethical problems
      from which emerged a three-component basic nature and 10 content categories. This
      paper reports the content categories. The findings provide understanding of the
      content of PWAs' ethical problems and suggest the importance of ethical listening
      as an independent nursing intervention.

PMID- 7811986
TI  - Evaluating interventions for fear of contagion.
AB  - Fear of contagion, an anxious response to the perceived threat of catching HIV,
      has been shown to lessen with contact with persons with AIDS. Two different
      continuing educational offerings presented a panel of persons living with HIV as
      an intervention to decrease fear of contagion. Presession and postsession
      questionnaires demonstrated a significant decrease in levels of fear in the one
      day program (n = 39), but not in the six-week course (n = 14). Willingness to
      care for those with HIV was unchanged in either offering. The study provides
      evidence for the effectiveness of exposure to persons living with HIV to decrease
      fear of contagion, even in a sample that had low fear scores initially.

PMID- 7811985
TI  - Infections related to venous access devices in patients with AIDS.
AB  - The use of implanted venous access devices (VADs) for long-term administration of
      medications and fluids in HIV/AIDS patients has become common. This retrospective
      study compared infection rates in implanted external catheters and totally
      implanted ports. The study also investigated possible relationships between
      infection, type of VAD, frequency of use, compliance, home care, frequency of
      clinic visits, and number of inpatient hospital days. The sample consisted fo 48
      AIDS patients with a total of 54 VADs. The external catheters had an infection
      rate of 36.5%, while the ports had an infection rate of 30.8%. A significant
      relationship was found between lack of compliance with care of the VAD and
      infection rates.

PMID- 7811987
TI  - Advances in the biology and treatment of B-cell chronic lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in the
      western hemisphere. Diagnosis and staging of CLL are usually straightforward, but
      predicting an individual patient's prognosis is still a challenge. Cytogenetic
      abnormalities provide important prognostic information in CLL and may show its
      molecular heterogeneity. A search for oncogene abnormalities continues, although
      no consistent defects have been identified. New agents such as fludarabine
      produce high complete remission rates and have generated interest in earlier
      treatment as a first step in a potential cure. Fludarabine also makes autologous
      bone marrow transplant feasible as a consolidation therapy. Immunologic
      abnormalities and minimal residual disease persist in most patients in remission.
      Combining fludarabine with other active agents and devising effective
      postremission strategies may change the natural history of CLL.

PMID- 7811988
TI  - The CD11b promoter directs high-level expression of reporter genes in macrophages
      in transgenic mice.
AB  - CD11b is the alpha chain of the Mac-1 integrin and is preferentially expressed in
      myeloid cells (neutrophils, monocytes, and macrophages). We have previously shown
      that the CD11b promoter directs cell-type-specific expression in myeloid lines
      using transient transfection assays. To confirm that these promoter sequences
      contain the proper regulatory elements for correct myeloid expression of CD11b in
      vivo, we have used the -1.7-kb human CD11b promoter to direct reporter gene
      expression in transgenic mice. Stable founder lines were generated with two
      different reporter genes, a Thy 1.1 surface marker and the Escherichia coli lacZ
      (beta-galactosidase) gene. Analysis of founders generated with each reporter
      demonstrated that the CD11b promoter was capable of driving high levels of
      transgene expression in murine macrophages for the lifetime of the animals.
      Similar to the endogenous gene, transgene expression was preferentially found in
      mature monocytes, macrophages, and neutrophils and not in myeloid precursors.
      These experiments indicate that the -1.7 CD11b promoter contains the regulatory
      elements sufficient for high-level macrophage expression. This promoter should be
      useful for targeting heterologous gene expression to mature myeloid cells.

PMID- 7811989
TI  - The first mutation identified in the thrombomodulin gene in a 45-year-old man
      presenting with thromboembolic disease.
AB  - Thrombomodulin (TM) is the anticoagulant endothelial cell membrane-bound protein
      cofactor in the thrombin-mediated activation of protein C (PC). It has been
      clearly demonstrated that the anticoagulant and profibrinolytic functions of the
      PC system are important for the prevention of a thromboembolic disease. Patients
      with PC, protein S, or PC "'cofactor"' deficiency and/or dysfunction develop
      thromboembolic diseases. However, the molecular abnormality in at least 20% to
      30% of thrombophilic patients cannot be identified by hitherto recognized
      defects. A putative pathologic lesion in the TM gene could be one of several
      candidates for these prothrombotic mutations. A directed search strategy for
      deletions, insertions, or point mutations in the TM gene has not been performed.
      Therefore, in the present study, we have analyzed the entire TM gene, including
      the promoter region, by polymerase chain reaction-single-strand conformation
      polymorphism (PCR-SSCP) in normal healthy volunteers and in patients presenting
      with a thromboembolic disease. We have identified a patient with a thromboembolic
      disease and a TM point mutation. In a 45-year-old Hispanic man with a documented
      pulmonary embolism, PCR-SSCP showed an aberrant band pattern and subsequent DNA
      sequence analysis showed a heterozygous substitution for G1456 to T. This
      substitution predicts an Asp468 to a Tyr change in the amino acid sequence that
      is located between the transmembrane domain and the sixth epidermal growth factor
      like domain. The Asp468 to Tyr change would probably lead to significant
      structural changes not allowing the expression of the TM protein or to a
      conformational change that is not functional.

PMID- 7811990
TI  - Downregulation of neutrophil CD43 by opsonized zymosan.
AB  - CD43, a prevalent white blood cell molecule distinguished by its mucin-like
      surface region, has been proposed as a "functional barrier" that prevents or
      negatively regulates a variety of cell surface interactions. Implicit in this
      hypothesis is the expectation that CD43 will be altered or removed when white
      blood cells are activated. To investigate alterations of CD43 in a dramatic
      example of functional cell activation, suspension neutrophils were challenged
      with opsonized zymosan, a characterized stimulator of phagocytosis and
      respiratory burst oxidase. Flow cytometry showed decreased surface density of
      CD43 in opsonized zymosan-treated neutrophils, and immune precipitation showed
      decreased cellular CD43 content, indicating that opsonized zymosan downregulates
      CD43 by a proteolytic mechanism. Based on densitometry of immune precipitates,
      CD43 levels were decreased 42% +/- 6% in neutrophils treated for 10 minutes with
      opsonized zymosan and decreased 70% +/- 3% in neutrophils treated with phorbol 12
      myristate 13-acetate (PMA). CD43 downregulation in response to opsonized zymosan,
      like PMA-induced CD43 downregulation, was insensitive to the serine protease
      inhibitor diisopropylfluorophosphate (DFP). In contrast, CD43 downregulation in
      response to opsonized zymosan or PMA was prevented by 4-(2-aminoethyl)
      benzenesulfonylfluoride (AEBSF) and 3'4'-dichloroisocoumarin (3,4-DCI), both of
      which are characterized serine protease inhibitors. Activation of the neutrophil
      respiratory burst oxidase by opsonized zymosan or PMA was also insensitive to DFP
      and prevented by AEBSF and 3,4-DCI. These findings indicate a requirement for a
      proteolytic step in activation of the respiratory burst of intact suspension
      neutrophils by opsonized zymosan and PMA and suggest that CD43 cleavage may be a
      required proteolytic event.

PMID- 7811991
TI  - Tec protein-tyrosine kinase is involved in interleukin-3 signaling pathway.
AB  - Among cytoplasmic protein-tyrosine kinases (PTKs) Tec now forms a novel subfamily
      with recently identified Tec-related PTKs (Btk and Itk/Tsk). Tec is known to be
      abundantly expressed in myeloid cells, and multiple forms of Tec protein can be
      generated via the mechanism of alternative splicing. In this report, we have
      investigated 5'-terminal diversity of the tec messages to demonstrate a
      predominant form of the Tec protein in mouse hematopoietic cell lines. Using anti
      Tec serum, we could show that stimulation with interleukin-3 (IL-3) can induce
      tyrosine phosphorylation of Tec both in myeloid and pro-B-cell lines. IL-3
      stimulation was also shown to induce kinase activity of Tec. Furthermore, we
      could demonstrate that Tec is constitutively associated with the Shc protein in
      vivo. Thus, we conclude that Tec is involved in the signaling pathway of IL-3.

PMID- 7811992
TI  - Pulse cyclophosphamide therapy for refractory autoimmune thrombocytopenic
      purpura.
AB  - Autoimmune thrombocytopenic purpura (AITP) is generally a chronic disorder in
      affected adults. Twenty-five percent of these patients will become refractory to
      routine therapy (corticosteroids and splenectomy), as well as most other
      available agents. Intravenous pulse cyclophosphamide therapy was used to treat 20
      patients with severe refractory AITP who had previously failed to achieve a
      sustained remission with a mean of 4.8 agents (range 2 to 8). Patients received 1
      to 4 doses (mean 2.0) of 1.0 to 1.5 g/m2 intravenous cyclophosphamide per course.
      Of the 20 patients treated with pulse cyclophosphamide therapy, 13 patients (65%)
      achieved a complete response (CR), four (20%) a partial response (PR), and three
      patients (15%) failed to respond. Of the 13 complete responders, eight have
      remained in remission with stable platelet counts during followup intervals of 7
      months to 7 years (median 2.5 years). Five patients developed recurrent AITP 4
      months to 3 years following a CR. Of these, two patients responded to subsequent
      courses of pulse cyclophosphamide therapy with current remissions of 1 and 4
      years. Of the four patients who obtained a PR, two remain in partial remission
      after 10 months and 4 years; one relapsed after 18 months and, after retreatment,
      is still in remission at 6 months. Of the patient characteristics examined,
      duration of disease was most strongly associated with response to pulse
      cyclophosphamide. Side-effects of treatment included neutropenia (three patients,
      one of whom developed staphylococcal sepsis), acute deep venous thrombosis (two
      patients), and psoas abscess (one patient). Intravenous pulse cyclophosphamide
      should be strongly considered in the treatment of patients with refractory AITP.
      There is a relatively low incidence of side-effects, and it can be administered
      easily on an out-patient basis.

PMID- 7811994
TI  - Differential regulation of macrophage differentiation in response to leukemia
      inhibitory factor/oncostatin-M/interleukin-6: the effect of enforced expression
      of the SCL transcription factor.
AB  - The physiologic program of macrophage differentiation normally proceeds in a
      coordinated manner in response to several different growth factors. Although the
      utilization of common receptor subunits may explain in part overlapping biologic
      functions, mechanisms by which unique actions are mediated remain obscure. We
      examined growth factor-induced macrophage differentiation in M1 leukemia cells
      that simultaneously display receptors for interleukin-6 (IL-6), leukemia
      inhibitory factor (LIF) and Oncostatin-M (OSM). Differentiation induced by all
      three factors was associated with decreased expression of transcription factors
      myb and SCL, increased expression of macrophage markers, and suppression of
      proliferation. Cell lines were established in which SCL expression was enforced.
      In the absence of growth factors, cells were indistinguishable from parental
      cells. However, LIF (or OSM)-induced macrophage differentiation was perturbed;
      there was failure to undergo morphologic differentiation, disturbed expression of
      lysozyme and Mac1 alpha, and failure to suppress proliferation. Surprisingly the
      perturbation of macrophage differentiation did not apply to induced expression of
      macrophage colony-stimulating factor (M-CSF) or granulocyte colony stimulating
      factor (G-CSF) receptors. This dissociation of elements normally coordinated in a
      macrophage differentiation program applied at a clonal level. There was no
      disturbance of IL-6-induced macrophage differentiation. These data directly
      implicate SCL in components of the macrophage differentiation program (suggesting
      that LIF receptor/gp130 heterodimers utilize an SCL-inhibitable pathway while
      gp130 homodimers do not) and demonstrate differential-regulation of components of
      the mature macrophage phenotype.

PMID- 7811993
TI  - Regulation of apoptosis induced by the retinoid N-(4-hydroxyphenyl) retinamide
      and effect of deregulated bcl-2.
AB  - The cancer chemopreventive retinoid N-(4-hydroxyphenyl)-all-trans retinamide
      (HPR) was recently shown by us to have antiproliferative and apoptotic effects on
      human leukemic cell lines, including those unresponsive to all-trans retinoic
      acid (ATRA). We have now characterized further the process of HPR-induced cell
      death. We report that inhibitors of RNA transcription and of protein synthesis,
      activators of protein kinase C (PKC), inhibitors of tyrosine kinases, Zn++, and
      the antioxidants acetylcysteine, ascorbic acid, alpha-tocopherol, and
      deferoxamine suppressed HPR-induced apoptosis. HL60 cells induced toward
      monocytic differentiation by 1,25 dihydroxyvitamin-D3 [1,25(OH)2D3], but not
      those induced toward the granulocytic differentiation by ATRA, showed reduced
      responses to HPR. The transport of HPR by cells with different sensitivity to the
      retinoid, however, was similar, even after treatment with the phorbol ester 12-O
      tetradecanoylphorbol-13-acetate (TPA), which induces unresponsiveness to HPR. The
      expression of the apoptosis-related genes bcl-2, p53, and c-myc was examined to
      determine their role in HPR-triggered cell death. The levels of bcl-2 mRNA were
      markedly diminished by 24 hours of HPR treatment in all cell lines except in the
      relatively HPR-insensitive line K422. However, probably because of its long half
      life, bcl-2 protein levels were either unchanged or only slightly decreased.
      Downregulation of p53 mRNA was also observed within 24 hours of HPR exposure in
      NB4 but not K422 cells, but no changes in the amount of p53 protein were found.
      Suppression of c-myc transcription was observed in all cells except K422. The
      protective role of bcl-2 on cell death by HPR was investigated in HL60 as well as
      697 pre-B leukemia and Jurkat T-acute lymphocytic leukemia (T-ALL) cells
      constitutively expressing high levels of bcl-2 proteins due to gene transfer
      manipulation. Compared with control cells, the onset of apoptosis in these cells
      with deregulated bcl-2 production was delayed by at least 24 hours. These
      findings establish that cell death by HPR requires RNA transcription and protein
      synthesis and is regulated by the activation of PKC. Although changes in bcl-2,
      p53, and c-myc expression are found in cells treated with HPR, the time-course of
      these events suggests that HPR-triggered apoptosis is not directly controlled by
      these genes. Finally, while ectopic overexpression of bcl-2 does not protect
      cells from death by HPR, it markedly delays its onset.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7811995
TI  - Neutralization of heparin activity by neutrophil lactoferrin.
AB  - Lactoferrin is a prominent component of neutrophil secondary granules, and its
      blood concentration is increased in certain inflammatory diseases. In contrast to
      the well-described biochemical characterization of lactoferrin as an iron-binding
      protein, its physiologic role in the regulation of inflammation and other host
      defense mechanisms is unclear. In this report, we provide evidence that
      lactoferrin has a potent heparin-neutralizing activity during thrombin inhibition
      by the serine proteinase inhibitors (serpins) antithrombin and heparin co-factor
      II. Activated neutrophil supernatant, which contains lactoferrin and other
      heparin-binding proteins, could neutralize the heparin-dependent antithrombin
      thrombin inhibition reaction. The addition of lactoferrin to plasma corrected the
      heparin-induced prolongation of blood plasma coagulation as measured by the
      activated partial thromboplastin time (aPTT). Treatment of whole blood with
      specific inflammatory mediators, fMLP, lipopolysaccharide (LPS), and tumor
      necrosis factor-alpha (TNF-alpha) increased the concentration of both plasma
      lactoferrin and platelet factor 4 while inhibiting the blood anticoagulant
      activity of heparin as measured by the aPTT. These results suggest that the
      prothrombotic sequelae of some inflammatory processes may be partly due to
      various agonists that release neutrophil lactoferrin, which can then neutralize
      glycosaminoglycan-dependent serpin-thrombin inhibition reactions.

PMID- 7811996
TI  - One of the two common mutations causing factor XI deficiency in Ashkenazi Jews
      (type II) is also prevalent in Iraqi Jews, who represent the ancient gene pool of
      Jews.
AB  - In recent years four mutations causing factor XI deficiency have been identified
      in Jews of Ashkenazi (European) origin. Two of them, type II (a nonsense
      mutation) and type III (a missense mutation), were found to prevail among 125
      unrelated Ashkenazi Jews with severe factor XI deficiency. A finding of type II
      mutation in four unrelated Iraqi-Jewish families raised the possibility that this
      mutation is also common in Iraqi Jews, who represent the ancient gene pool of the
      Jews. A molecular-based analysis performed in 1,040 consecutively hospitalized
      patients disclosed the following results: Among 531 Ashkenazi-Jewish patients,
      the type II allele frequency was 0.0217 and among 509 Iraqi-Jewish patients,
      0.0167 (P = .50). The type III allele frequency in the Ashkenazi-Jewish patients
      was 0.0254, whereas none of 502 Iraqi-Jewish patients examined had this mutation.
      These data suggest that the type II mutation was present in Jews already 2.5
      millenia ago. The data also indicate that the estimated risk for severe factor XI
      deficiency in Ashkenazi Jews (due to either genotype) is 0.22% and in Iraqi Jews,
      0.03%, and that the estimated risk of heterozygosity in Ashkenazi Jews is 9.0%
      and in Iraqi Jews, 3.3%. As patients with severe factor XI deficiency are prone
      to bleeding after injury and patients with partial deficiency may have similar
      bleeding complications when an additional hemostatic derangement is present, the
      observed high frequencies should be borne in mind when surgery is planned for
      individuals belonging to these populations.

PMID- 7811997
TI  - Interferon-alpha induces circulating tumor necrosis factor receptor p55 in
      humans.
AB  - In the present studies we investigated the effect of interferon-alpha (IFN alpha)
      on the release of the soluble (extracellular) form of the tumor necrosis factor
      p55 receptor (TNFsRp55), because TNFsRp55 is a natural antagonist of tumor
      necrosis factor (TNF)-induced inflammation and also might be part of the
      antiinflammatory properties of IFN alpha. Plasma levels of TNFsRp55 were measured
      by a specific radioimmunoassay in five healthy volunteers and in five patients
      with chronic hepatitis C treated with IFN alpha. Levels showed a significant
      increase after a single injection of 5.0 million U IFN alpha in both healthy and
      hepatitis patient groups. Peak values (3.5 to 4.5 ng/mL) were observed within 12
      hours of beginning treatment. Thereafter, levels promptly declined, reaching
      baseline values within 24 hours. TNF alpha and C-reactive protein (CRP) levels
      were below the detection limit in the same plasma samples. In addition, IFN alpha
      suppressed significantly interleukin (IL)-1 alpha-induced TNF alpha protein
      synthesis by human peripheral blood mononuclear cells. These results suggest that
      the antiinflammatory properties of IFN alpha may be, in part, also due to the
      induction and/or release of TNF soluble receptors and the suppression of TNF
      alpha synthesis.

PMID- 7811998
TI  - A new staging system for multiple myeloma based on the number of S-phase plasma
      cells.
AB  - In the present study, we analyzed the cell cycle distribution of bone marrow (BM)
      cells in 120 untreated multiple myeloma patients using a DNA/CD38 double-staining
      technique at flow cytometry in which plasma cells (PCs) can be clearly
      discriminated from residual BM cells based on their CD38 expression. This
      approach allows us to determine the proliferative activity of both PCs and
      residual normal BM cells. The percentage of S-phase cells in the myelomatous
      population was found to be significantly lower than that of the residual normal
      BM cells (P < .001). Regarding the proliferative activity of myelomatous cells,
      patients with a high number of S-phase PCs (> 3%) showed a significantly (P <
      .05) increased incidence of anemia and hypercalcemia; higher values of beta 2
      microglobulin (beta 2M), urea, and creatinine; and higher numbers of peripheral
      blood natural killer cells, as well as a poor prognosis as assessed both by
      response duration and overall survival. With respect to the residual BM normal
      fraction, a low proliferative activity was significantly (P < .05) associated
      with the presence of anemia and neutropenia together with increased numbers of BM
      PCs, a higher incidence of Bence Jones myelomas, and DNA diploidy. Multivariate
      analysis showed that the number of S-phase PCs was the most important independent
      prognostic factor, allowing us to discriminate two subgroups of patients with
      different prognoses, even within the same clinical stage. Moreover, the S-phase
      PCs, together with beta 2M, age, and performance status, represent the best
      combination of disease characteristics for stratifying patients according to
      prognosis and allow the establishment of a simple and powerful staging system for
      multiple myeloma patients. In addition, this classification can be used for
      planning treatment in patients who are candidates for transplantation.

PMID- 7811999
TI  - Model of Epstein-Barr virus infection of human thymocytes: expression of viral
      genome and impact on cellular receptor expression in the T-lymphoblastic cell
      line, HPB-ALL.
AB  - Infection of B lymphocytes and epithelial tissue by Epstein-Barr virus (EBV) is
      associated with malignancy and autoimmunity. The cellular receptor for EBV has
      been identified as CD21 (CR2). A molecule, which is biochemically and
      immunologically similar to B-cell CD21, has been identified on a subpopulation of
      immature thymocytes, suggesting a role for this molecule in the regulation of T
      cell development and further suggesting that immature T cells might be
      susceptible to EBV infection. A growing body of literature now documents the
      presence of EBV in tumors of T-cell origin. We have evaluated the susceptibility
      of the human immature T cell line, HPB-ALL, to infection by EBV. Electron
      microscopy studies showed a rapid internalization of virus by HPB cells. Southern
      blotting showed the intracellular presence of linear EBV genomes, and components
      of the virus replicative cycle were identified. Expression of the BamHI Z region
      of the genome, encoding the nuclear protein, ZEBRA, which is strictly associated
      with productive infection in B cells, was detected in HPB-ALL cells. A spliced
      variant of Z, RAZ, was also identified. Cell surface expression of EBV late
      antigens was observed to occur transiently. Infection of HPB cells was also
      accompanied by altered expression of T-cell surface molecules involved in antigen
      recognition, a process critical to normal development of the T-cell repertoire.
      Delineation of the outcome of T-cell infection by EBV may lead to a better
      understanding of the role of this virus in autoimmune processes and malignancy.

PMID- 7812001
TI  - The proto-oncogene c-fgr is expressed in normal mantle zone B lymphocytes and is
      developmentally regulated during myelomonocytic differentiation in vivo.
AB  - The proto-oncogene c-fgr is a member of the c-src gene family of cytoplasmic
      tyrosine kinases. Previous studies have suggested that it is normally expressed
      in neutrophils, monocytes, macrophages, and natural killer cells. c-fgr is also
      expressed in the B cells of certain lymphoproliferative disorders, namely,
      Epstein-Barr virus-associated lymphoproliferative disease, and in chronic
      lymphocytic leukemia, but it has not previously been detected in normal or
      reactive human lymphoid tissue. In this study we have determined the pattern of
      p55c-fgr protein expression in normal human hematopoietic and lymphoid tissues at
      the single-cell level using immunohistochemical and immunofluorescent techniques.
      We show that p55c-fgr expression is developmentally regulated with high-level
      expression first evident at the myelocyte stage of myeloid differentiation. In
      addition, we show that p55c-fgr is expressed in circulating B lymphocytes
      isolated from chronic lymphocytic leukemia patients but is not expressed in
      normal circulating B lymphocytes. Surprisingly, p55c-fgr is also expressed in a
      subpopulation of normal B lymphocytes, the mantle zone B lymphocytes. This
      demonstration that p55c-fgr is expressed in a normal B-lymphocyte subpopulation
      suggests that its expression in certain B-cell lymphoproliferative disorders may
      be an indirect consequence of, rather than a primary cause of, the neoplastic
      transformation process.

PMID- 7812000
TI  - Inhibition of cellular differentiation by the SCL/tal oncoprotein:
      transcriptional repression by an Id-like mechanism.
AB  - In cases of T-cell acute lymphoblastic leukemia (T-ALL), the basic helix-loop
      helix (bHLH) oncogene SCL/tal undergoes frequent rearrangements activating
      ectopic expression. Despite the compelling epidemiological association of SCL/tal
      expression with T-ALL, no specific transforming function has been attributable to
      the protein product. However, investigators have recently demonstrated that
      forced overexpression of SCL/tal can block monocytic differentiation of M1 murine
      myeloid leukemia cells. Thus, inappropriate expression of wild-type SCL/tal
      protein may in part account for the maturation arrest phenotype observed in T-ALL
      cells. In this study, ectopic expression of the SCL/tal gene blocked the
      differentiation of C2C12 muscle precursor cells. Characterization of the
      mechanism of differentiation blockade showed that the SCL/tal protein repressed
      transcriptional activation by the myogenic bHLH factor MyoD. Protein interaction
      analysis showed that SCL/tal and MyoD compete for common partners (E bHLH
      proteins) but do not directly bind one other. A model is thus proposed in which
      ectopic SCL/tal protein, by its ability to titrate out E proteins, prevents the
      formation of bHLH complexes that drive cellular differentiation: the "Id-like"
      mechanism.

PMID- 7812002
TI  - Lack of the expression of EBNA-2 and LMP-1 in T-cell neoplasms possessing Epstein
      Barr virus.
AB  - We investigated 34 cases of T-cell neoplasm [15 cases of T-cell granular
      lymphocytic leukemia (T-GLL), 10 cases of T-cell non-Hodgkin's lymphoma (T-NHL),
      six cases of T-cell chronic lymphocytic leukemia (T-CLL), and three cases of
      cutaneous T-cell lymphoma] to study their association with Epstein-Barr virus
      (EBV). In 4 (three T-NHL and one T-GLL) of 34 cases, EBV genome was detected in a
      single episomal form, while polyclonal EBV-DNA was detected in one (T-NHL) of the
      remaining cases. All three cases of T-NHL having monoclonal EBV episome showed
      histologically diffuse large-cell lymphoma and developed leukemic conversion.
      Phenotypic analysis showed that two of these four cases were CD4+, CD8-, and the
      remaining two cases were CD4-, CD8+. The cells from all four cases were confirmed
      to be in T-cell lineage by detecting the rearrangement of T-cell receptor (TCR)
      beta or gamma chain gene. By reverse transcription-polymerase chain reaction (RT
      PCR), EBNA-1 was detected at low levels, and neither EBNA-2 nor LMP-1 were found
      in any of the three cases examined. Lack of the expression of EBNA-2 and LMP-1
      was also confirmed by immunocytochemical staining. The cells of these four cases
      did not show rearrangement or overexpression of c-myc and bcl-2 genes by Southern
      and Northern blots, and the mutation of p53 gene was detected in only one
      patient. These results suggest that other latent gene products of EBV or other
      cellular oncogenes are involved in the development of Japanese T-cell neoplasm
      after EBV infection.

PMID- 7812003
TI  - Differentiation of early plasma cells on bone marrow stromal cells requires
      interleukin-6 for escaping from apoptosis.
AB  - The bone marrow (BM) is well known to be the major site of Ig production in
      secondary immune responses; thus, the microenvironment of BM is considered to be
      essential for final differentiation of plasma cells. We identified in the
      peripheral blood (PB) early plasma cells (CD38++CD19+VLA-5-) committed to
      entering the BM. The sorted early plasma cells rapidly entered apoptosis in
      vitro, but these cells could survive and further differentiate into mature plasma
      cells (CD38 CD19+) just as BM plasma cells in the presence of a BM-derived
      stromal cell line (KM-102). Culture supernatants of KM-102 cell lines could also
      support survival of these cells, and antibody to interleukin-6 (IL-6) completely
      blocked the effect of these supernatants. Furthermore, recombinant IL-6, but not
      IL-1 or IL-3, could support their survival and their differentiation into mature
      plasma cells (CD38 CD19+VLA-5+) with expression of VLA-5 mRNA. Therefore, here is
      direct evidence that early plasma cells found in the PB differentiated into
      mature plasma cells with stromal cell-derived IL-6 in vitro; thus, BM stromal
      cells control the final checkpoint of plasma cell differentiation with secretion
      of IL-6 in the BM.

PMID- 7812004
TI  - Detection of residual leukemic cells in patients with acute promyelocytic
      leukemia by the fluorescence in situ hybridization method: potential for
      predicting relapse.
AB  - The translocation between chromosomes 15 and 17, t(15;17)(q22-24;q11-21), is
      present in the bone marrow cells of most patients with acute promyelocytic
      leukemia (APL). Although conventional cytogenetic methods are useful for
      diagnosing this disease, difficulties are experienced in detecting residual
      disease among those patients who have achieved remission. In this study, we used
      the fluorescence in situ hybridization (FISH) method to attempt to detect
      residual leukemic cells in 10 APL patients in clinical remission. The duration of
      remission ranged from 2 to 93 months at the time of study. Multiple bone marrow
      samples were analyzed by FISH in most patients. In 6 patients, no cell with
      t(15;17) was found. These patients remain in complete remission at present
      (approximately 25 to 33 months since first studied by FISH). In 4 patients, low
      frequencies of cells with t(15;17) were observed in at least one bone marrow
      sample examined. All of these patients relapsed within 1 to 14 months. No cell
      with t(15;17) was identified by the conventional G-banding method in any sample.
      The FISH results correlated well with that of a two-round nested reverse
      transcription polymerase chain reaction assay that was performed on the same
      samples. Thus, our study suggests that FISH is potentially a useful tool for
      detecting residual APL cells and for identifying patients at high risk of
      relapse.

PMID- 7812005
TI  - Elevated dihydrofolate reductase and impaired methotrexate transport as elements
      in methotrexate resistance in childhood acute lymphoblastic leukemia.
AB  - A retrospective study of clinical resistance to methotrexate (MTX) was performed
      on 29 archival specimens of frozen lymphoblasts obtained from children with acute
      lymphoblastic leukemia (ALL), including 19 at initial presentation and 10 at
      first relapse. Blasts were assayed for dihydrofolate reductase and MTX transport
      by flow cytometry using the fluorescent methotrexate analog, PT430 (Rosowsky et
      al, J Biol Chem 257:14162, 1982). In contrast to tissue culture cells, patient
      blasts were often heterogeneous for dihydrofolate reductase content. Of the 19
      specimens at initial diagnosis, 7 exhibited dual blast populations, characterized
      by threefold to 10-fold differences in relative dihydrofolate reductase; the
      dihydrofolate reductase-overproducing populations comprised 12% to 68% of the
      total blasts for these specimens. Remission duration intervals for patients
      exhibiting dual blast populations were notably shorter than for patients
      expressing a single blast population with lower dihydrofolate reductase ( < or =
      9 months v > or = 15 months, respectively), a difference that was statistically
      significant (P = .045). There was no apparent correlation between expression of
      increased dihydrofolate reductase at diagnosis and known patient and disease
      prognostic features (immunophenotype, age, sex, and white blood count). For the
      relapsed patients, 4 of 10 exhibited dual lymphoblast populations with elevated
      dihydrofolate reductase. The majority of the patient lymphoblast specimens were
      entirely competent for MTX transport and, likewise, expressed immunoreactive
      reduced folate carriers by indirect immunofluorescence staining with specific
      antiserum to the transporter. Three patients (2 at relapse and 1 at diagnosis)
      exhibited heterogeneous expression of imparied MTX transport (14% to 73% of
      blasts). In only 1 of these patients did the majority of the lymphoblasts (73%)
      show impaired MTX transport and for this specimen, immunoreactive carrier
      proteins were virtually undetectable. These results suggest that heterogeneous
      expression of elevated dihydrofolate reductase and impaired MTX transport are
      important modes of resistance in childhood ALL patients undergoing chemotherapy
      with MTX and that these parameters may serve as predictive indices of clinical
      response to MTX.

PMID- 7812006
TI  - Differential expression levels of the heat shock protein 27 isoforms in pediatric
      normal, nonleukemic and common acute lymphoblastic leukemia B-cell precursors.
AB  - Heat shock protein 27 (hsp27) may function as a regulator of microfilament
      dynamics and may participate in signal transduction pathways of different cell
      growth regulators, with the mitogen-activated protein kinase-activated protein
      (MAPKAP) kinase 2 being a major enzyme responsible for its phosphorylation. Using
      two-dimensional gel electrophoresis, we have compared the expression levels of
      two hsp27 isoelectric variants (hsp27 isoforms) M2 (molecular weight, 26 kD;
      isoelectric point, 6.02) and M3 (molecular weight, 26 kD; isoelectric point,
      5.60) in pediatric bone marrow CD19+CD10+B-cell precursors (BCPs) purified from
      either common acute lymphoblastic leukemia (c-ALL) patients, normal donors, or
      non-c-ALL patients. Compared with normal BCPs, we found increased hsp27
      expressions (M2 isoform) (by a factor 5 to 9 of mean level) in c-ALL as well as
      in non-c-ALL (nonleukemic) precursors. Though increased phosphorylation of hsp27
      (M3 isoform) was observed in BCPs from c-ALL patients at relapse (by a factor 3
      of mean level compared with normal BCPs and precursors from c-ALL at diagnosis),
      which might represent a differential enzymatic activity, this was not
      distinguishable from that of non-c-ALL patients. Therefore, our studies suggest
      constitutive differences of hsp27 isoforms between pediatric leukemic BCPs and
      their relatively low-expressing, immunophenotypically normal bone marrow
      counterparts. In light of the occasional and possibly transient increase of hsp27
      expression during nonleukemic BCP differentiation and the possible role of hsp27
      in signal transduction to microfilaments, these differences might be of
      considerable biologic interest and of importance in future studies of regulated
      normal or dysregulated leukemic hematopoietic cellular differentiation.

PMID- 7812008
TI  - Human neutrophils lose their surface Fc gamma RIII and acquire Annexin V binding
      sites during apoptosis in vitro.
AB  - We have previously reported that neutrophilic granulocytes rapidly release part
      of their Fc gamma RIII from the plasma membrane upon in vitro activation,
      probably by proteolytic cleavage. In plasma and other body fluids, released or
      soluble Fc gamma RIII has been found in considerable amounts. In the present
      study, neutrophils were kept in maintenance culture for 18 to 24 hours. Forty
      percent of the neutrophils completely lost Fc gamma RIII, and the remainder of
      the cells showed a 60% decrease in Fc gamma RIII expression on their surface.
      Released Fc gamma RIII was detected in the culture supernatant. Nevertheless,
      more than 90% of the cells was viable as judged by hydrolysis of fluorescein
      diacetate. The presence of interferon gamma, granulocyte colony-stimulating
      factor, or granulocyte-macrophage colony-stimulating factor, but not interleukin
      3 (IL-3), IL-6, or IL-8, in the culture medium increased the number of cells that
      still expressed Fc gamma RIII. We found that this loss of Fc gamma RIII was not
      the result of cell activation but correlated strongly with apoptosis. The Fc
      gamma RIII-negative subpopulation exhibited typical morphologic changes, such as
      nuclear condensation and DNA fragmentation. Furthermore, this subpopulation
      appeared to have acquired the property of binding Annexin V, a calcium-dependent,
      phospholipid-binding protein with high affinity for phosphatidylserine. The
      external exposure of this phospholipid by cells has been reported to occur during
      apoptosis. The property of Annexin V binding was not shared by the nonapoptotic,
      Fc gamma RIII-positive subpopulation. In this respect, we identified binding of
      Annexin V as an convenient marker for apoptotic cells. Our results indicate that
      soluble Fc gamma RIII in body fluids might be derived for a large part from
      neutrophils undergoing apoptosis in the tissues.

PMID- 7812007
TI  - Diverging signal transduction pathways activated by interleukin-8 and related
      chemokines in human neutrophils: interleukin-8, but not NAP-2 or GRO alpha,
      stimulates phospholipase D activity.
AB  - Interleukin-8 (IL-8) and the structurally related cytokines neutrophil-activating
      peptide-2 (NAP-2) and GRO alpha are powerful chemotactic agents for human
      neutrophils. Although these three chemokines act by binding to overlapping but
      not identical receptor subsets, the data available to date have stressed the
      similarities in their mechanisms of action. The present studies were undertaken
      to further our understanding of the signal transduction mechanisms associated
      with these neutrophil agonists. IL-8, NAP-2, and GRO alpha stimulated similar
      increases in the level of cytoplasmic free calcium. They were also shown to
      stimulate qualitatively similar increases in the levels of protein tyrosine
      phosphorylation. In contrast, only IL-8 enhanced the formation of
      phosphatidylethanol (PEt), the product catalyzed by phospholipase D (PLD) in the
      presence of ethanol. The formation of PEt stimulated by IL-8 was inhibited by
      pertussis toxin and the tyrosine kinase inhibitors erbstatin and herbimycin A.
      The ability of IL-8 to stimulate the activity of PLD was additively enhanced, or
      primed, by cytochalasin B and by tumor necrosis factor alpha. Although all three
      chemokines increased the level of free cytoplasmic calcium to the same extent, IL
      8 was significantly more potent than either NAP-2 or GRO alpha with respect to
      its ability to enhance CD11b expression and to stimulate chemotactic and
      oxidative responses. The differences between IL-8, NAP-2, and GRO alpha in their
      ability to stimulate PLD is likely to be related to their respective binding
      affinities for the two IL-8 receptors (IL-8R-A and IL-8R-B). These results
      suggest that the signalling pathways activated by IL-8R-A and IL-8R-B diverge at
      a step preceding the activation of PLD.

PMID- 7812009
TI  - Changes in the blood group Wright antigens are associated with a mutation at
      amino acid 658 in human erythrocyte band 3: a site of interaction between band 3
      and glycophorin A under certain conditions.
AB  - The Wright (Wr) blood group antigens, Wra and Wrb, have been suggested to be
      determined by alleles of the same gene. The Wrb antigen appears to involve both
      red blood cell (RBC) band 3 and glycophorin A (GPA). We have examined the cDNA
      sequences of the band 3 and GPA of one of the two known Wr(a+b-) individuals. We
      show that this individual is homozygous for the mutation Glu658-->Lys in band 3,
      but has normal GPA. Putative heterozygotes with Wr(a+b+) RBCs have both Glu and
      Lys at residue 658 of band 3, whereas the common Wr(a-b+) RBC phenotype only have
      band 3 with Glu658. The Wra and Wrb antigens are determined by the amino acid at
      residue 658 of band 3 and are antithetical. Examination of the amino acid
      sequence and Wrb antigen expression of GPA-related hybrid glycophorins suggests
      that Arg61 of GPA interacts with Glu658 of band 3 to form the Wrb antigen. We
      suggest that the interaction is stabilized by the presence of anti-Wrb antibodies
      and that this site of association between GPA and band 3 may be responsible for
      the previously reported ability of anti-GPA antibodies to decrease the
      deformability of RBCs.

PMID- 7812010
TI  - Striking inverse correlation between IgG anti-F(ab')2 and autoantibody production
      in patients with cold agglutination.
AB  - Previous experiments showed that the physiologic IgG anti-F(ab')2 antibody
      suppresses the response of human autoreactive B cells. In the present study, we
      analyzed the IgG anti-F(ab')2 antibody in 293 patients with cold agglutination
      (CA). Their average IgG anti-F(ab')2 titer was not much different (211 +/- 8.3)
      from that of 279 healthy persons (195 +/- 6.7). However, CA patients with high
      anti-F(ab')2 titers had low CA autoantibody titers and vice versa (P = .0028; rho
      = -0.175). The stratification of patients according to the auto-antibody's
      specificity (anti-I, anti-i, anti-Pr) showed an inverse correlation between anti
      F(ab')2 and CA in the anti-I group (P = .0057; rho = -0.180). Interestingly, the
      association was present only in patients whose disease was caused by
      noninfectious agents (P < .0001; rho = -0.423). The inverse correlation argues
      for an important role of the IgG anti-F(ab')2 in the regulation of autoantibody
      production in CA patients.

PMID- 7812012
TI  - Autologous bone marrow transplantation for first remission acute myeloblastic
      leukemia in patients older than 50 years: a retrospective analysis of the
      European Bone Marrow Transplant Group.
AB  - High-dose chemotherapy, with or without radiotherapy, followed by autologous stem
      cell rescue is used increasingly for the intensification of first remission in
      acute myeloblastic leukemia (AML). However, these treatments have been limited to
      young patients due to the increased risks of regimen-related toxicities and
      mortality with age. Several investigators have recently published the upper age
      limit for autologous bone marrow transplant (ABMT) in AML because of encouraging
      results. The results of ABMT for AML were studied in 111 patients > or = 50 years
      of age intensified in first remission. Median age at transplant was 53 years
      (range, 50 to 63 years). Fifty patients were conditioned with total body
      irradiation and 61 with polychemotherapy: 23 with busulfancyclophosphamide, 11
      with the University College Hospital (UCH; London, UK) regimen, 6 with BAVC, and
      21 with various other treatments. Marrow was purged in only 11 cases. Results
      were compared with 786 ABMTs performed for AML in patients between 16 and 49
      years of age (median, 35 years). For AML in first remission, the probability of
      leukemia-free survival (LFS) at 4 years was 34% +/- 5% for patients aged 50 years
      or more and 43% +/- 2% for patients less than 50 years of age (P = .004), with a
      survival probability of 35% +/- 6% and 48% +/- 2%, respectively (P = .004). The
      probability of relapse was not significantly different between the two groups
      (52% +/- 7% v 50% +/- 2%), but transplant-related mortality was significantly
      higher in the older age group (28% +/- 5% v 14% +/- 2%; P < .0001) and mainly due
      to infectious complications. In a multivariate analysis, age less than 50 years
      was a favorable risk factor for LFS, treatment-related mortality (TRM), and
      survival but not for relapse incidence. These data suggest that ABMT should be
      considered in older AML patients.

PMID- 7812011
TI  - Correlative morphologic and molecular genetic analysis demonstrates three
      distinct categories of posttransplantation lymphoproliferative disorders.
AB  - The posttransplantation lymphoproliferative disorders (PT-LPDs) are a
      morphologically heterogeneous group of Epstein-Barr virus (EBV)-driven lymphoid
      proliferations of varying clonal composition. Some PT-LPDs regress after a
      reduction in immunosuppression, while others progress in spite of aggressive
      therapy. Previously defined morphologic categories do not correlate with
      clonality, and neither morphology nor clonality has reliably predicted the
      clinical behavior of PT-LPDs. We investigated 28 PT-LPD lesions occurring in 22
      patients for activating alterations involving the bcl-1, bcl-2, c-myc, and H-, K-
      and N-ras proto-oncogenes and for mutations involving the p53 tumor suppressor
      gene. We correlated the results of these studies with the morphology of the
      lesions, their clonality based on Ig heavy and light chain gene rearrangement
      analysis, and the presence and clonality of EBV infection. We found that the PT
      LPDs are divisible into three distinct categories as follows: (1) plasmacytic
      hyperplasia: most commonly arise in the oropharynx or lymph nodes, are nearly
      always polyclonal, usually contain multiple EBV infection events or only a minor
      cell population infected by a single form of EBV, and lack oncogene and tumor
      suppressor gene alterations; (2) polymorphic B-cell hyperplasia and polymorphic B
      cell lymphoma: may arise in lymph nodes or various extranodal sites, are nearly
      always monoclonal, usually contain a single form of EBV, and lack oncogene and
      tumor suppressor gene alterations; and (3) immunoblastic lymphoma or multiple
      myeloma: present with widely disseminated disease, are monoclonal, contain a
      single form of EBV, and contain alterations of one or more oncogene or tumor
      suppressor genes (N-ras gene codon 61 point mutation, p53 gene mutation, or c-myc
      gene rearrangement). The PT-LPDs are divisible into three categories exhibiting
      distinct morphologic and molecular genetic characteristics. Alterations involving
      the N-ras and c-myc proto-oncogenes and the p53 tumor suppressor gene may play an
      important role in the development and/or progression of the PT-LPDs.

PMID- 7812013
TI  - Bone marrow transplantation in major histocompatibility complex class II
      deficiency: a single-center study of 19 patients.
AB  - Major histocompatibility complex (MHC) class II deficiency (bare lymphocyte
      syndrome) is a rare inborn error of the immune system characterized by impaired
      antigen presentation and combined immunodeficiency. It causes severe and
      unremitting infections leading to progressive liver and lung dysfunctions and
      death during childhood. As in other combined immunodeficiency disorders, bone
      marrow transplantation (BMT) is considered the treatment of choice for MHC class
      II deficiency. We analyzed the files of 19 patients who have undergone BMT in our
      center. Of the 7 patients who underwent HLA-identical BMT, 3 died in the
      immediate posttransplant period of severe viral infections, whereas the remaining
      4 were cured, with recovery of normal immune functions. Of the 12 patients who
      underwent HLA-haplo-identical BMT, 3 were cured, 1 was improved by partial
      engraftment, 7 died of infectious complications due to graft failure or
      rejection, and 1 is still immunodeficient because of engraftment failure. A
      favorable outcome in the HLA-non-identical BMT group was associated with an age
      of less than 2 years at the time of transplantation. All the patients with stable
      long-term engraftment had persistently low CD4 counts after transplantation (105
      to 650/microL at last follow up), but no clear susceptibility to opportunistic
      infections despite persisting MHC class II deficiency on thymic epithelium and
      other nonhematopoietic cells. We conclude that HLA-identical and -haploidentical
      BMT can cure MHC class II deficiency, although the success rate of haploidentical
      BMT is lower than that in other combined immunodeficiency syndromes. HLA
      haploidentical BMT should preferably be performed in the first 2 years of life,
      before the acquisition of chronic virus carriage and sequelae of infections.

PMID- 7812014
TI  - Specificity of BCR-ABL antisense oligonucleotides.

PMID- 7812015
TI  - Guidelines for management of hemophilia A and B.

PMID- 7812016
TI  - A skewed lyonization phenomenon as cause of hemophilia A in a female patient.

PMID- 7812017
TI  - Interleukin-2 after T-cell-depleted allogeneic bone marrow transplantation.

PMID- 7812018
TI  - Glucose-6-phosphate dehydrogenase deficiency in sickle cell disease by DNA
      analysis.

PMID- 7812019
TI  - Carer burden after proximal femoral fracture.
AB  - This carer study forms part of a wider study which compares accelerated
      rehabilitation after proximal femoral fracture with conventional care. Two
      measures of burden on family caregivers were used; social worker's assessment of
      overall burden and an index of disruption to carers' lives. Participants were
      carers of 200 patients interviewed at five periods up to 12 months after
      fracture. Carer burden prior to the fracture was the strongest predictor of
      subsequent burden, with carers of patients in nursing homes and patients with a
      cognitive or physical disability being more burdened. Carer burden may increase
      or decrease after the patient's injury, irrespective of randomization group.
      There is no simple relationship between burden and randomized group. Accelerated
      rehabilitation does not impact greatly on carer burden, but already severely
      burdened carers may benefit from additional counselling/information. Specific
      ways in which carers; lives were disrupted are reported.

PMID- 7812020
TI  - Subjective weighting of disability: an approach to quality of life assessment in
      rehabilitation.
AB  - The impact of various disabilities may differ greatly from individual to
      individual. Therefore, for a full assessment of a rehabilitee, objective aspects
      of disability should be supplemented with disability perception. The purpose of
      this study was to construct a self-administered questionnaire of 39
      abilities/activities based on the ICIDH D-code, with parallel questions about
      '(dis)ability' and 'impact'. The instrument was used to obtain data from 60
      disabled people. Fifty forms (83%) were returned from 25 patients with spinal
      cord injury and 25 patients with rheumatoid arthritis. Mean time to fill out the
      questionnaire was 24 minutes. A first attempt to validate the 'weighted score'
      with an open question about the most negative aspects of the disease showed a
      (very) good correspondence in 74%. An information gain as a result of the impact
      question was noted in 44%. This instrument has attractive properties for clinical
      use and research purposes in rehabilitation medicine. It was developed for the
      identification of needs of individual patients. The 'weighted scores' allow the
      setting of priorities in an individually tailored rehabilitation programme.
      Future applications might include monitoring the progress of a rehabilitee and
      identification of group needs.

PMID- 7812021
TI  - On non-work activity preferences: relationships with occupational roles.
AB  - Occupational therapy is to a great extent based on the idea of engaging patients
      in meaningful activities. Using mailed checklists this investigation examines the
      preference attached to 50 activities by 201 adult (25-55 years old) northern
      Swedes using a four-grade ordinal scale. The self-reported levels of activity
      preferences were related to age and gender. Factor analysis was used to analyse
      the inter-relationships between activity preferences. The possible effects of
      activity preferences on self-reported occupational role internalization (10
      items) were examined using discriminant analyses. Activity preferences were
      gender-dependent for more than half of the activities while only 14 of them were
      age-dependent. The factor analysis grouped 41 of the activities into 15 factors
      which were labelled 'activity goals'. Fourteen of these were distinct classifiers
      (discriminant analyses) of the self-reported degree of internalization of 8/10
      occupational roles. In this sample occupational role internalization has
      elsewhere been demonstrated to be closely related to several domains of life
      satisfaction, which in turn are closely associated with satisfaction with life as
      a whole. Taken together with those results the present investigation leads the
      authors to suggest this model: activity preferences-->occupational roles-->domain
      specific life satisfaction-->happiness.

PMID- 7812022
TI  - Mobility function of the elderly living with their children and its relation to
      the home health care system in Tokyo.
AB  - Most elderly in Japan prefer living with their children once their spouse passes
      away. In comparison with western countries, home health care systems have
      developed quite differently in Japan. The traditional practice of the elderly
      living with their children is, however, changing. In 1989 we carried out a mail
      questionnaire survey focused on the relationship between mobility functions of
      the elderly living in Tokyo and their rate of living with family members. The
      subjects for the present analysis were 2368 widows and widowers. Under the group
      category 'independent in long walks', 72.8% were living with their families. With
      a decrease in mobility functions, this percentage rose to 81.1 and 84.6, although
      it decreased to 50.9 in the group with severely impaired mobility functions. The
      need to develop effective social services for families housing their parents is
      discussed.

PMID- 7812023
TI  - Goals in rehabilitation teamwork.
AB  - 'Goal setting' is used in rehabilitation team management as a tool to improve the
      quality of the rehabilitation process. In general, goals must be relevant,
      expressing what should be accomplished, positively defined, put in behavioural
      terms, easily and clearly understood by all the team members, attainable, allow
      planning, and they must be measurable. Goals should be set in terms of activities
      of value to the patient, to be realized in a planned timespan.

PMID- 7812024
TI  - Kaposi's sarcoma and AIDS in Uganda: its frequency and gastrointestinal
      distribution.
AB  - The frequency and distribution of gastrointestinal Kaposi's sarcoma were
      investigated in 63 consecutive AIDS patients. The main risk factor for AIDS was
      heterosexual intercourse. Gastrointestinal lesions were found in 24 cases
      (38.1%): 12 patients (11.1%) had both upper and lower GI tract involvement, 7
      patients (11.1%) had only oesophago-gastroduodenal lesions and 5 (7.9%) only
      lower tract disease. Our results show that in heterosexual Africans, the tumours
      closely resemble the tumours of western homosexuals in endoscopic appearance, in
      being multicentric and in the gastro-intestinal tract involved. We conclude that
      even in the heterosexual African AIDS population, the gastrointestinal tract is
      frequently involved and this phenomenon, if more widely studied might give us new
      elements about the aetiophatogenesis of Kaposi's sarcoma which is still unclear.

PMID- 7812025
TI  - Intermittent versus continuous 5-aminosalicylic acid treatment for maintaining
      remission in ulcerative colitis.
AB  - We performed a 12-month clinical trial to compare the relative effectiveness of
      an intermittent 5-ASA regimen and a continuous 5-ASA regimen for the maintenance
      treatment of patients with ulcerative colitis in remission. Fifty patients with
      ulcerative colitis in remission for a minimum period of 1 month participated in
      the study. Twenty five patients received an intermittent treatment with 5-ASA
      tablets (2.4 g for the first week of each month) and 25 received a continuous
      treatment with tablets (1.6 g each day). Patients were assessed clinically every
      two months and endoscopically every 6 months. Our results show that the two
      treatments were equally effective. The relapse-free rates at 12 months were 71%
      in patients receiving the intermittent treatment and 66% in patients given the
      continuous treatment. This difference is not statically significant. Further
      studies are needed to assess whether the intermittent regimen can be an
      alternative to life-long treatment in patients who have maintained remission for
      a long period of time.

PMID- 7812026
TI  - Prospective study of the incidence of ultrasound-detected hepatic hematomas due
      to percutaneous Menghini needle liver biopsy and laparoscopy-guided Silverman
      needle biopsy.
AB  - Recently, a high incidence of sonographically detected hepatic hematomas
      following percutaneous liver biopsy and laparoscopy-guided liver biopsy has been
      reported. For this reason a prospective study in 178 patients was performed. The
      patients were examined by ultrasound before and 24 hours after percutaneous liver
      biopsy using the 1.4 mm-Menghini needle (n = 107) and by laparoscopically-guided
      biopsy with the 2.5 mm-Silverman needle (n = 71). Four of the 107 patients (4%)
      who underwent percutaneous Menghini biopsy displayed hepatic hematoma on
      ultrasonography, and in 2 of these cases the hematoma was > 6 cm in diameter and
      persisted for more than seven months. In the group of patients who underwent
      laparoscopy-guided Silverman biopsy (n = 71) a liver hematoma occurred twice
      (3%). Both hematomas were small and disappeared within several days. There was no
      need for special therapeutic interventions due to complications. In contrast to
      recent data about Tru-cut and JAM-Shidi biopsy, the results of this study
      indicate that percutaneous Menghini biopsy and laparoscopy-guided Silverman
      biopsy are relatively safe diagnostic procedures.

PMID- 7812027
TI  - Intravariceal pressure measurement in cirrhotic patients: is it a reliable
      technique?
AB  - The aim of the present study is to evaluate in both "in vitro" and clinical
      conditions the reliability of the method for measuring the oesophageal varices
      pressure by means of a sclerosing needle. The perfusion system was validated "in
      vitro", comparing the tracings obtained with two different perfusion apparatus,
      with two different perfusional agents and with the needle either completely or
      partially inserted in a venous catheter perfused with saline solution, either in
      the same direction as the flow or the opposite one. The clinical validation was
      conducted on 14 cirrhotic patients with II to IV grade oesophageal varices
      according to Dagradi's classification. During endoscopy, the intravariceal and
      oesophageal pressures were measured using a sclerosing needle, perfused with
      hydrosoluble contrast medium. Once the intravariceal pressure measurement was
      completed, an X-ray film of the chest was performed. The data were evaluated
      considering the absence of visible contrast medium as evidence of correct
      intravariceal needle position, and the presence of a roundish image as evidence
      of paravariceal insertion of the needle. The presence of respiratory oscillations
      and intravariceal pressure values were verified in manometric tracings and were
      compared with radiological findings. The "in vitro" tests showed no differences
      in the pressure recording obtained using different pumps, different perfusion
      agents and with different manners of inserting the needle. Only twenty-eight of
      the manometric recordings were considered adequate for evaluation in clinical
      conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7812028
TI  - IgM anti-HCV core in HCV-RNA positive subjects with and without chronic liver
      disease.

PMID- 7812029
TI  - Nodular regenerative hyperplasia of the liver: ultrasonographic appearance and
      echo-guided bioptic diagnosis.
AB  - Nodular regenerative hyperplasia of the liver is characterized by multiple and
      usually small nodules of hyperplastic hepatocytes surrounded by compressed
      atrophic liver cells. Given the small size of nodules and the preserved
      framework, the imaging techniques often show a normal liver and blind
      percutaneous biopsy is misinterpreted. The Authors report two cases of nodular
      regenerative hyperplasia diagnosed by ultrasound and percutaneous echoguided
      biopsy.

PMID- 7812030
TI  - Eosinophilic gastroenteritis in a patient with large-cell anaplastic lung
      carcinoma: a paraneoplastic syndrome?
AB  - A 39-year-old man was hospitalized with abdominal pain and diarrhoea. The total
      eosinophil count was 11,800/dL; the jejunal biopsy showed diffuse and patchy
      eosinophils and plasma cell infiltration of the lamina propria; symptoms and
      hypereosinophilia disappeared after steroid therapy. Two months later the
      symptoms reappeared together with left supraclavicular lymphnode enlargement. The
      chest X-ray showed a mass within the left lung apex. Lymph node biopsy showed
      metastases from large-cell anaplastic carcinoma. The possibility of eosinophilic
      gastroenteritis as a paraneoplastic manifestation is discussed.

PMID- 7812031
TI  - Intraluminal duodenal diverticulum.
AB  - A 76-year-old man with an iron deficiency anemia during the previous 4 years and
      recent melena was presented. Gastroscopy showed a sessile polypoid lesion in the
      area of the papilla of Vater and histology was normal. Barium swallow follow
      through and CT scan revealed a round intraluminal filling defect. ERCP
      demonstrated extrinsic compression of both ducts. Emergency laparotomy was
      performed because of upper GI bleeding and because attempts at endoscopic
      haemostasis of the oozing polypoid mass were unsuccessful. A soft compressible
      polypoid mass was found, which on palpation excreted a viscous milky liquid
      through a tiny opening. Histology showed normal duodenal mucosa bilaterally, a
      diagnostic finding of intraluminal duodenal diverticulum. The atypical age of
      presentation as well as gastroscopic and roentgenographic findings of this rare
      entity are illustrated.

PMID- 7812032
TI  - Helicobacter pylori and chronic gastritis: anatomico-functional correlations.

PMID- 7812033
TI  - Classification of the enteric nerve cells of the porcine small intestine into two
      subpopulations using enzyme histochemical techniques.
AB  - Using acetylcholinesterase (AChE), nicotinamide adenine dinucleotide diaphorase
      (NADHd), and nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd)
      enzyme histochemical techniques, the ganglionated plexuses of the porcine enteric
      nervous system were investigated in small intestine whole-mount preparations.
      Both AchE and NADHd techniques revealed a majority of the neurons in the ganglia
      of all three major plexuses. The AchE technique also demonstrated clearly the
      axodendritic networks of the plexus myentericus. Intraganglionic blank areas
      revealed the localization of negative cell groups. A very high correlation was
      found between the activity of both enzymes in one neuron, although this
      correlation was certainly not linear. Many neurons exhibited a stronger signal
      for one enzyme. A very small part of the positive nerve cells showed intense
      staining for both AchE and NADHd. The NADPHd technique demonstrated that the
      NADPHd-positive neurons fill the negative intraganglionic spaces in the ganglia.
      Double staining with the two other enzymes showed virtually no colocalization of
      NADPHd with either NADHd or AchE in the porcine jejunal enteric ganglia. Little
      negative intraganglionic spaces were seldom found, leaving room for perhaps still
      more negative enteric neurons. Based upon these results we suggest that the
      enteric neurons of the porcine small intestine can be subdivided into AchE-NADHd
      and NADPHd subpopulations. Since the latter colocalizes with the neuronal NO
      synthase enzyme, we further suggest a subdivision of the enteric nerve cells into
      AchE-NADHd and NOS-NADHd neurons.

PMID- 7812034
TI  - Chemosensitivity, plasticity, and functional heterogeneity of paraganglionic
      cells in the rat coeliac-superior mesenteric complex.
AB  - Chemosensitivity and plasticity of paraganglionic cells in the rat coeliac
      superior mesenteric complex (CSMC) were investigated at a basal state of normoxia
      (21% O2) and after long-term moderate hypoxia (10% O2, 14 days). Chemical
      sympathectomy previous to hypoxia was performed to destroy principal ganglionic
      neurons and thus to allow measurement of the norepinephrine and dopamine content
      of paraganglionic cells. At the basal state, the CSMC contained dopaminergic
      (TH+/DBH-) and noradrenergic (TH+/DBH+) paraganglionic cells, the majority being
      of the noradrenergic type. After 14 days of hypoxia, this ratio was reversed and
      dopaminergic cells predominated, as indicated by a twofold increase of TH+ cells
      and a twofold decrease of DBH+ cells. Biochemically, hypoxia produced an increase
      in the content (1.6-fold) and utilization (1.4-fold) of dopamine as well as a
      smaller increase in the content of norepinephrine, with no change in its
      utilization rate. The dopaminergic activation induced by hypoxia persisted after
      sympathectomy with guanethidine. It is concluded that paraganglionic cells in the
      CSMC display a chemosensitive function. Furthermore, our findings indicate that
      paraganglionic cells are differentially affected by hypoxia, depending on their
      distribution and the nature of their neuromodulators. The alterations induced by
      hypoxia point out the phenotypic plasticity developed by paraganglionic cells in
      adaptation to hypoxia and further demonstrate the functional heterogeneity of
      this autonomic cell population in the rat CSMC.

PMID- 7812035
TI  - Immunohistochemistry of small intensely fluorescent (SIF) cells and of SIF cell
      associated nerve fibers in the rat superior cervical ganglion.
AB  - Double-labelling immunofluorescence was applied on single sections of the rat
      superior cervical ganglion to evaluate neurochemistry and connectivity of
      intraganglionic SIF cells. The synaptic vesicle membrane protein synaptophysin
      and secretoneurin, a newly discovered neuropeptide derived from secretogranin II,
      proved reliable molecular markers of this cell type, whereas serotonin and
      tyrosine hydroxylase immunoreactivities were observed in slightly incongruent SIF
      cell subpopulations. Immunolabelling for vasoactive intestinal polypeptide and
      neuropeptide Y occurred in few SIF cells. None of the above immunoreactivities
      were visibly altered by preganglionic or postganglionic denervation, while some
      SIF cells were immunolabelled for galanin or for the neuronal microtubule
      associated protein MAP2 after postganglionic denervation. SIF cells were
      nonreactive for the pan-neuronal marker protein gene product (PGP) 9.5 or
      neurofilament 160 kD. Intense staining of NADPH-diaphorase in some SIF cells,
      suggesting catalytic activity of nitric oxide synthase, could not be
      substantiated by immunoreactivity for this enzyme. SIF cells were approached by
      nonidentical fiber populations immunoreactive for PGP 9.5, neurofilament, or
      neuropeptide Y, whereas immunoreactivities for galanin and vasoactive intestinal
      polypeptide were colocalized in fiber meshes around SIF cells. The findings
      indicate (1) neurochemical SIF cell heterogeneity, (2) SIF cell plasticity in
      response to ganglionic perturbation, and (3) a differentiated innervation of SIF
      cells in the rat superior cervical ganglion.

PMID- 7812036
TI  - Adrenal medulla and Parkinson's disease.
AB  - Parkinson's disease has been described as a multisystem disorder that includes
      alterations in the function of the autonomic nervous system. The activity of the
      adrenal medulla in this disease has not been thoroughly investigated. Previous
      reports are reviewed that demonstrate that the adrenal medullae of parkinsonian
      patients are compromised, having a decreased content of all catecholamines and
      several neuropeptides. An animal model was used to investigate whether the
      observations made in human patients were related to extended treatment with
      antiparkinsonian medications or were a natural concomitant of the disease.
      Administration of L-dopa and/or carbidopa to C57BL mice for 4-16 weeks had no
      significant effect on the level of any of the adrenal medullary catecholamines.
      Treatment with MPTP 4-16 weeks prior to sacrifice did not deplete adrenal
      medullary catecholamines in these animals, thus not fully mimicking Parkinson's
      disease in this animal model. The only significant effect was an interaction
      between group (MPTP or control) and treatment with antiparkinsonian medications;
      L-dopa, in the absence and presence of carbidopa, had opposite effects in the two
      groups. Based primarily on the lack of effect of antiparkinsonian medications on
      adrenal medullary catecholamines, it was concluded that the adrenal medullary
      depletion observed in human patients was a peripheral concomitant of Parkinson's
      disease.

PMID- 7812037
TI  - Adrenal medulla in neural grafting and neural plasticity.
AB  - The recent history of neural transplantation using the adrenal medulla parallels
      an evolution in our thinking about neural grafting as a therapeutic approach to
      treat neurodegenerative diseases such as Parkinson's disease. Initially, neural
      grafting was an approach to study development and regeneration. With the
      discovery that adrenal chromaffin cell grafts would ameliorate some of the motor
      deficits associated with the loss of striatal dopamine, adrenal grafts were used
      to provide dopamine to the dopamine-depleted striatum. However, subsequent
      studies showed poor chromaffin cell survival unless trophic factors were present
      at the site of transplantation. These experiments lead to the appreciation of the
      complex interactions between neurotrophic factors, inflammatory cytokines, the
      grafted tissue, and the host brain's response. Thus, we find ourselves again
      using neural transplantation as an approach to help us better understand central
      nervous system plasticity and the features this plasticity shares in common with
      development and regeneration.

PMID- 7812038
TI  - Morphological observations of small granule-containing (chromaffin) cells in the
      celiac ganglion of the guinea pig, with emphasis on cell contacts.
AB  - Utilizing electron microscopic observation, several contacts between small,
      granule-containing cells (SGC) and postganglionic neurons (PGN) in the celiac
      ganglion of the guinea pig have been observed. A SGC in very close association
      with a PGN was seen to receive a distinct synaptic contact that contained many
      vesicles with dense cores. This contact was morphologically unlike cholinergic
      synapses previously reported on chromaffin cells. Because the SGC and PGN were
      clearly separated by a thin rim of satellite cell cytoplasm mutual to both cells,
      it is not known how or if the SGC would possibly exert a synaptic or paracrine
      effect on the PGN. Also, intraganglion SGC existed as large well-vascularized
      islands within the celiac ganglion. These intraganglion clusters sometimes
      contained more than 50 cells and perhaps could be considered to function as
      localized neuroendocrine components within the ganglion by secreting granule
      products into the nearby blood vessels for local or distant effects, although
      this certainly is not known. This work reports a unique synaptic ending upon a
      single-occurring SGC, which, in turn, closely approximates a ganglion neuron in a
      soma-somatic relationship. In addition, a very close association (but no actual
      contact) was observed between granule-containing processes, presumably emanating
      from the intraganglion clusters, and PGN. Whatever the function of ganglionic SGC
      may be, the exact relationship between SGC and PGN presumably would be of great
      interest and potential importance.

PMID- 7812039
TI  - Autonomic nervous system structures: structural and functional correlates.
      Introduction.

PMID- 7812040
TI  - Analysis of the mechanism for acetylcholine release at the synapse formed between
      rat sympathetic neurons in culture.
AB  - Superior cervical ganglion neurons (SCGNs) were isolated from 7-day-old rat SCG
      and cultured in MEM containing horse serum, fetal calf serum, and nerve growth
      factor. In this culture condition, it is well known that the SCGNs form
      cholinergic synapse. In 3-4 weeks cultured neurons, immunofluorescent staining
      for synaptophysin, a small synaptic vesicle associated protein, showed the
      presence of synaptophysin as small dots on the surface of the soma. Postsynaptic
      potentials could be recorded in 50-80% of the neurons responding to evoked action
      potentials elicited in neighboring neurons. Because of its relatively large cell
      size and the short distance to the terminal, this synapse is a useful model for
      studying the mechanisms of acetylcholine (ACh) release by introducing substances
      such as antibodies or selective inhibitors into the presynaptic neuron by means
      of the whole-cell clamp technique. In this model synapse we tested the possible
      role of myosin in ACh release. The distribution of myosin was studied by the
      immunofluorescent staining technique. Myosin was recognized by the anti-myosin II
      IgG at the same synaptic terminals that showed the presence of synaptophysin with
      its antibody. The functional blockade of myosin by the antibody itself, and that
      of myosin light chain kinase (MLCK) by a pseudosubstrate inhibitor of MLCK, SM-1,
      or by a selective inhibitor of MLCK, wortmannin, induced depression of synaptic
      transmission in a dose-dependent manner. These indicate that phosphorylation of
      myosin by MLCK may be necessary for ACh release mechanisms.

PMID- 7812041
TI  - Cell cycle-regulated degradation of Xenopus cyclin B2 requires binding to
      p34cdc2.
AB  - The protein kinase activity of the cell cycle regulator p34cdc2 is inactivated
      when the mitotic cyclin to which it is bound is degraded. The amino (N)-terminus
      of mitotic cyclins includes a conserved "destruction box" sequence that is
      essential for degradation. Although the N-terminus of sea urchin cyclin B confer
      cell cycle-regulated degradation to a fusion protein, a truncated protein
      containing only the N-terminus of Xenopus cyclin B2, including the destruction
      box, is stable under conditions where full length molecules are degraded. In an
      attempt to identify regions of cyclin B2, other than the destruction box,
      involved in degradation, the stability of proteins encoded by C-terminal deletion
      mutants of cyclin B2 was examined in Xenopus egg extracts. Truncated cyclin with
      only the first 90 amino acids was stable, but other C-terminal deletions lacking
      between 14 and 187 amino acids were unstable and were degraded by a mechanism
      that was neither cell cycle regulated nor dependent upon the destruction box.
      None of the C-terminal deletion mutants bound p34cdc2. To investigate whether the
      binding of p34cdc2 is required for cell cycle-regulated degradation, the behavior
      of proteins encoded by a series of full length Xenopus cyclin B2 cDNA with point
      mutations in conserved amino acids in the p34cdc2-binding domain was examined.
      All of the point mutants failed to form stable complexes with p34cdc, and their
      degradation was markedly reduced compared to wild-type cyclin. Similar results
      were obtained when the mutant cyclins were synthesized in reticulocyte lysates
      and when cyclin mRNA was translated directly in a Xenopus egg extract. These
      results indicate that mutations that interfere with p34cdc2 binding also
      interfere with cyclin destruction, suggesting that p34cdc2 binding is required
      for the cell cycle-regulated destruction of Xenopus cyclin B2.

PMID- 7812042
TI  - The release of parathyroid hormone and the exocytosis of a proteoglycan are
      modulated by extracellular Ca2+ in a similar manner.
AB  - Secretion of parathyroid hormone (PTH) is regulated in part by a classical
      "stimulus-secretion" pathway responsive to catecholamines. The primary
      physiological modulator of PTH exocytosis in parathyroid cells, however, is
      extracellular free Ca2+. Ca(2+)-modulated PTH release exhibits several
      characteristics suggestive of constitutive secretion. The aim of this work was to
      obtain further information about the possible intracellular origins of Ca(2+)
      modulated exocytosis in parathyroid cells. Freshly dissociated bovine parathyroid
      cells labeled with [35S]sulfate synthesized a soluble chondroitin/dermatan
      sulfate proteoglycan (M(r) approximately 90-150 K) that was secreted into the
      medium. The export of [35S]sulfated proteoglycan satisfied several criteria that
      generally define constitutive release: 1) export is detected in the medium
      shortly (7-15 min) after a 5-min pulse, 2) there is minimal intracellular storage
      after equilibrium labeling (because of combined processes of rapid release and
      intracellular degradation), and 3) there is insensitivity to stimulation with
      isoproterenol, a known secretagogue in parathyroid cells. Nevertheless, the
      increase in extracellular Ca2+ from 0.5 to 2.0 mM reduced the export of the
      [35S]sulfated proteoglycan from 60% of total labeled to 30%. In addition, a
      secreted pool of immunoreactive PTH and [35S]sulfated proteoglycan was modulated
      by external Ca2+ to the same degree and sensitivity, although isoproterenol was
      more effective in stimulating the release of PTH than that of proteoglycan.
      Together, our experimental results show that in the parathyroid cell
      extracellular Ca2+ modulates negatively the export of both PTH and proteoglycan,
      a putative marker for constitutive secretion. We further suggest that a portion
      of newly synthesized PTH also enters this pathway, whereas another portion
      proceeds to an isoproterenol-releasable compartment from which the proteoglycan
      is largely excluded.

PMID- 7812043
TI  - Mutation of proline-1003 to glycine in the epidermal growth factor (EGF) receptor
      enhances responsiveness to EGF.
AB  - We have shown previously that the epidermal growth factor (EGF) receptor is
      phosphorylated at Ser-1002 and that this phosphorylation is associated with
      desensitization of the EGF receptor. Ser-1002 is followed immediately by Pro
      1003, a residue that may promote the adoption of a specific conformation at this
      site or severe as a recognition element for the interaction of the EGF receptor
      with other proteins. To examine these possibilities, we have mutated Pro-1003 of
      the EGF receptor to a Gly residue and have analyzed the effect of this mutation
      on EGF-stimulated signaling. Cells expressing the P1003G EGF receptors exhibited
      higher EGF-stimulated autophosphorylation and synthetic peptide phosphorylation
      compared to cells expressing wild-type EGF receptors. In addition, the ability of
      EGF to stimulate PI 3-kinase activity and mitogen-activated protein kinase
      activity was enhanced in cells expressing the P1003G EGF receptor. Cells
      expressing P1003G receptors also demonstrated an increased ability to form
      colonies in soft agar in response to EGF. These results indicate that mutation of
      Pro-1003 leads to a potentiation of the biological effects of EGF. The findings
      are consistent with the hypothesis that Pro-1003 plays a role in a form of
      regulation that normally suppresses EGF receptor function.

PMID- 7812044
TI  - The centromeric K-type repeat and the central core are together sufficient to
      establish a functional Schizosaccharomyces pombe centromere.
AB  - The DNA requirements for centromere function in fission yeast have been
      investigated using a minichromosome assay system. Critical elements of
      Schizosaccharomyces pombe centromeric DNA are portions of the centromeric central
      core and sequences within a 2.1-kilobase segment found on all three chromosomes
      as part of the K-type (K/K"/dg) centromeric repeat. The S. pombe centromeric
      central core contains DNA sequences that appear functionally redundant, and the
      inverted repeat motif that flanks the central core in all native fission yeast
      centromeres is not essential for centromere function in circular minichromosomes.
      Tandem copies of centromeric repeat K", in conjunction with the central core,
      exert an additive effect on centromere function, increasing minichromosome
      mitotic stability with each additional copy. Centromeric repeats B and L,
      however, and parts of the central core and its core-associated repeat are
      dispensable and cannot substitute for K-type sequences. Several specific protein
      binding sites have been identified within the centromeric K-type repeat,
      consistent with a recently proposed model for centromere/kinetochore function in
      S. pombe.

PMID- 7812045
TI  - Loss of cell cycle controls in apoptotic lymphoblasts of the bursa of Fabricius.
AB  - Lymphoblasts of the normal embryonic follicles of the chicken bursa of Fabricius
      undergo rapid apoptosis when exposed to gamma-radiation or when cell-cell
      contacts are disrupted by mechanical dispersion in short term culture. We have
      observed previously that overexpression of v-myc sensitizes preneoplastic bursal
      lymphoblasts to induction of cell death, whereas resistance to induced cell death
      is acquired during progression to neoplasia. In this study we observed extensive
      DNA degradation in the large majority of the lymphoblast population within the
      first hour after dispersion-induced apoptosis. Paradoxically these cells
      continued to progress into S-phase with the bulk of DNA cleavage and death
      occurring in S-phase cells (i.e., in cells with more than 2C and less than 4C DNA
      content). We confirmed the S phase status of apoptotic cells by determining that
      detection of nuclear cyclin A in individual cells also corresponded with
      detection of DNA breakage. Levels of cyclin E, cyclin E-dependent H1 histone
      kinase, and p53 proteins were maintained during dispersion-induced DNA cleavage.
      gamma-radiation failed either to inhibit cell cycle progression or to raise p53
      levels in dispersed bursal lymphoblasts. In intact bursal follicles low doses of
      gamma-radiation induced p53 whereas higher, apoptosis-inducing doses failed to
      induce p53 or prevent G1 to S-phase progression. These results suggest that
      normal DNA damage-induced cell cycle checkpoint controls are lost or overridden
      when apoptosis is induced in bursal lymphoblasts.

PMID- 7812046
TI  - Multiple N-ethylmaleimide-sensitive components are required for endosomal vesicle
      fusion.
AB  - This report examines the inhibition of endosomal vesicle fusion by the alkylating
      agent N-ethylmaleimide (NEM). The concentration of NEM required to inhibit
      vesicle fusion depended upon whether membrane and cytosolic fractions were
      treated separately or together, enabling the resolution of at least two
      components to the inhibition. The first component is inactivated at low levels of
      NEM when cytosolic and membrane fractions are treated together. On the contrary,
      inhibition of the second component required higher levels of NEM but was achieved
      by treating cytosol and membranes separately. Reconstitution studies indicated
      that both components were cytosolic and that neither corresponded to the
      ubiquitous NEM-sensitive fusion protein (NSF). The role of NSF in this fusion
      reaction was further examined using salt-washed membranes depleted of NSF
      protein. Under these conditions the fusion reaction was fully dependent upon
      added NSF whose activity, in this context, was sensitive to NEM treatment. From
      these data we conclude that NSF activity during endosomal vesicle fusion can be
      dissected into several steps, only a subset of which (perhaps attachment of NSF
      to the membrane) are sensitive to NEM. Fusion between salt-washed endosomal
      membranes was also dependent on soluble NSF attachment proteins.

PMID- 7812047
TI  - Inhibition of G2/M progression in Schizosaccharomyces pombe by a mutant
      calmodulin kinase II with constitutive activity.
AB  - Intracellular signaling by the second messenger Ca2+ through its receptor
      calmodulin (CaM) regulates cell function via the activation of CaM-dependent
      enzymes. Previous studies have shown that cell cycle progression at G1/S and G2/M
      is sensitive to intracellular CaM levels. However, little is known about the CaM
      regulated enzymes involved. Protein phosphorylation has been shown to be
      important for cell-cycle regulation. Because CaM regulates several protein
      kinases, and at least one protein phosphatase, our studies are focusing on the
      roles of these enzymes within the cell cycle. As an initial approach to this
      problem, cDNAs encoding either normal or mutant calcium/calmodulin kinase II
      (CaMKII) have been expressed in Schizosaccharomyces pombe. The results show that
      overexpression of a constitutively active mutant CaMKII caused cell-cycle arrest
      in G2. Arrest was associated with a failure to activate the p34/cdc2 protein
      kinase. Expression of the mutant CaMKII in strains of S. pombe with altered
      timing of mitosis revealed that this effect is not mediated either by cdc25+ or
      wee1+, suggesting that CaMKII may regulate G2/M progression by another mechanism.

PMID- 7812048
TI  - Members of the syndecan family of heparan sulfate proteoglycans are expressed in
      distinct cell-, tissue-, and development-specific patterns.
AB  - The syndecans are a gene family of four transmembrane heparan sulfate
      proteoglycans that bind, via their HS chains, diverse components of the cellular
      microenvironment. To evaluate the expression of the individual syndecans, we
      prepared cDNA probes to compare mRNA levels in various adult mouse tissues and
      cultured mouse cells representing various epithelial, fibroblastic, endothelial,
      and neural cell types and B cells at various stages of differentiation. We also
      prepared antibody probes to assess whether the extracellular domains of the
      individual syndecans are shed into the conditioned media of cultured cells. Our
      results show that all cells and tissues studied, except B-stem cells, express at
      least one syndecan family member; most cells and tissues express multiple
      syndecans. However, each syndecan family member is expressed selectively in cell
      , tissue-, and development-specific patterns. The extracellular domain of all
      syndecan family members is shed as an intact proteoglycan. Thus, most, if not
      all, cells acquire a distinctive repertoire of the four syndecan family members
      as they differentiate, resulting in selective patterns of expression that likely
      reflect distinct functions.

PMID- 7812051
TI  - The elusive quicksilver.

PMID- 7812052
TI  - Prevalence of positive urine drug screens in a prenatal clinic: correlation with
      patients' self-report of drug use.

PMID- 7812050
TI  - Phosphorylation and internalization of gp130 occur after IL-6 activation of Jak2
      kinase in hepatocytes.
AB  - Recent evidence has shown that members of the Jak kinase family are activated
      after IL-6 binds to its receptor complex, leading to a tyrosine phosphorylation
      of gp130, the IL-6 signal-transducing subunit. The different members of the IL-6
      cytokine subfamily induce distinct patterns of Jak-Tyk phosphorylation in
      different cell types. Using monospecific antibodies to gp130, Jak2 kinase, and
      phosphotyrosine, we investigated the kinetics of IL-6 stimulation of members of
      this pathway in primary hepatocytes. Our findings show that Jak 2 is maximally
      activated within 2 min of exposure to IL-6, followed by gp130 phosphorylation
      that reaches its peak in another 2 min then declines to basal level by 60 min. In
      vitro phosphorylation experiments show that activated Jak 2 is able to
      phosphorylate both native gp130 and a fusion peptide containing its cytoplasmic
      domain, demonstrating gp130 is a direct substrate of Jak 2 kinase. Experiments
      designed to explore the cell surface expression of gp130 show that > or = 2 h are
      required to get a second round of phosphorylation after the addition of more
      cytokines. This finding suggests that activated gp130 is internalized from the
      cell surface after IL-6 stimulation. Additional experiments using protein
      synthesis inhibitors reveal that new protein synthesis is required to get a
      second cycle of gp130 phosphorylation indicating gp130 must be synthesized de
      novo and inserted into the membrane. These findings provide strong evidence that
      down regulation of the IL-6 signal in hepatocytes involves the internalization
      and cytosol degradation of gp130.

PMID- 7812049
TI  - Yeast mitochondria contain ATP-sensitive, reversible actin-binding activity.
AB  - Sedimentation assays were used to demonstrate and characterize binding of
      isolated yeast mitochondria to phalloidin-stabilized yeast F-actin. These actin
      mitochondrial interactions are ATP sensitive, saturable, reversible, and do not
      depend upon mitochondrial membrane potential. Protease digestion of mitochondrial
      outer membrane proteins or saturation of myosin-binding sites on F-actin with the
      S1 subfragment of skeletal myosin block binding. These observations indicate that
      a protein (or proteins) on the mitochondrial surface mediates ATP-sensitive,
      reversible binding of mitochondria to the lateral surface of microfilaments.
      Actin copurifies with mitochondria during subcellular fractionation and is
      released from the organelle upon treatment with ATP. Thus, actin-mitochondrial
      interactions resembling those observed in vitro may also exist in intact yeast
      cells. Finally, a yeast mutant bearing a temperature-sensitive mutation in the
      actin-encoding ACT1 gene (act1-3) displays temperature-dependent defects in
      transfer of mitochondria from mother cells to newly developed buds during yeast
      cell mitosis.

PMID- 7812053
TI  - Evolving standards of practice for clinical cytogenetics.

PMID- 7812054
TI  - Recent advances in molecular cytogenetics: fluorescent in situ hybridization.

PMID- 7812055
TI  - Ileal pouch-anal anastomosis: the "ideal" operation for ulcerative colitis and
      adenomatous polyposis coli?

PMID- 7812056
TI  - Skier's thumb: a review.

PMID- 7812057
TI  - Physicians' obligations to withhold or withdraw life-sustaining medical
      treatment.

PMID- 7812058
TI  - Health insurance coverage among RI adults, 1993.

PMID- 7812060
TI  - Avoiding liability in contact lens practice.
AB  - Contact lens practice is the leading source of liability claims involving
      optometrists. Claims most often allege negligence, although informed consent or
      product liability may also be causes of legal claims for damages. For daily wear
      patients, the most likely causes of claims are nonapproved use of lenses or
      solutions, monovision contact lenses, negligence by a contact lens technician,
      failure to verify lenses before dispensing, mismanagement of contact lens-related
      corneal abrasions, and inadequate monitoring of ocular health. For extended-wear
      patients, the most common sources of liability claims are inappropriate patient
      selection, inadequate training of patients, improper wearing schedules, improper
      management of contact lens-related corneal complications, and inadequate
      monitoring of ocular health.

PMID- 7812059
TI  - Influenza: prevention and control.

PMID- 7812061
TI  - Rigid bifocal contact lenses.
AB  - Rigid bifocal contact lens options continue to improve, with several new designs
      available in both the simultaneous and alternating vision categories. This paper
      reviews the selection of bifocal lens patients, describes basic lens designs, and
      provides guidelines for the successful fitting of rigid bifocal lenses.

PMID- 7812062
TI  - Fitting hydrogel bifocal contact lenses.

PMID- 7812063
TI  - Extended-wear RGP contact lenses: a viable alternative to refractive surgery.
AB  - The rigid gas-permeable (RGP) extended-wear lens offers a unique alternative to
      the hydrogel extended-wear lens as well as to refractive surgery. In suitable
      patients it can provide almost maintenance-free visual correction for a wide
      variety of refractive errors. With prudent patient selection, use of high
      permeability RGP materials, sound lens design and fitting principles, and
      conservative follow-up procedures, RGP extended-wear lenses can have success
      rates exceeding those of either hydrogel extended-wear lenses or refractive
      surgery, with fewer complications. The complications that do occur are often
      predictable after a short period of daily wear, and the remainder can often be
      managed with small changes to lens design.

PMID- 7812064
TI  - The role of contact lenses in the management of the radial keratotomy patient.
AB  - Approximately 15% of radial keratotomy procedures result in a residual refractive
      error of at least 1.00 D. Contact lenses may be used in these cases to optimize
      visual acuity. Patients who have undergone radial keratotomy present unique
      physiological challenges because of the corneal incisions; wear of lenses can
      produce epithelial erosion, infiltrative keratitis, neovascularization, and
      chronic edema. The corneal topography is altered by the surgery, with the central
      cornea flattened and the midperiphery steepened; these changes influence contact
      lens design. The lens of choice is a large, thin, rigid gas-permeable lens with a
      fairly small optic zone. Hydrogel lenses can also be used, but complications of
      wear can include neovascularization and corneal edema. Toric hydrogel lenses can
      be used to minimize residual astigmatism.

PMID- 7812065
TI  - Cosmetics and contact lenses.
AB  - Cosmetics, as broadly defined, are used by almost all contact lens wearers of
      both sexes. Because of the composition of various cosmetic products, contact
      lenses can be soiled or damaged. The improper use of cosmetics can even cause
      damage to the eye. More commonly, allergic reactions occur that can jeopardize
      the continued wear of lenses. This paper reviews the complications that can
      occur, the available treatment options, and the recommendations for the safe and
      prudent use of cosmetics.

PMID- 7812066
TI  - Contact lens disinfection.
AB  - Contact lens disinfection plays an important role in both patient education and
      office management. Several methods of disinfection are available for protecting
      the contact lens wearer from contamination by a variety of organisms, but no one
      system is best suited to all lenses, patients, or situations. Furthermore, these
      disinfection agents are only one component in an effective lens care system.
      Essential also is thorough lens cleaning and rinsing as well as preventing lens
      case contamination. The practitioner needs to educate each patient for optimal
      lens care compliance at home, and to instruct staff on maintaining safe trial
      lenses in-office.

PMID- 7812067
TI  - Integrating disposable or planned replacement lenses into contact lens practice.
AB  - Disposable and planned replacement lenses have become increasingly popular
      options for contact lens wearers. Optometrists must devise management strategies
      to avoid the many problems that have emerged from the use of these lens
      modalities: inappropriate patient selection, reduced frequency of eye
      examination, oversupply of lenses, improper policies for the release of contact
      lens prescriptions, and inadequate documentation of service contracts.
      Suggestions are offered to avoid these common management problems.

PMID- 7812068
TI  - Recordkeeping and contact lens practice.
AB  - Recordkeeping in contact lens practice may be based on a problem-oriented system
      that emphasizes the use of forms. Fitting agreements and informed consent
      agreements are the most important components of such a system. Progress notes are
      also used to document the episodic care that is an integral part of contact lens
      practice. Examination findings should be described with descriptive language
      whenever possible; warnings, diagnoses, patient management, and recall and
      referral appointments should be conscientiously documented in the record of care.

PMID- 7812069
TI  - Management of contact lens prescriptions.
AB  - A patient's access to information in an optometrist's record is regulated by an
      amalgam of federal and state laws and judicial decisions. The inspection of
      records by patients is permitted except under extraordinary circumstances, and
      optometrists who refuse access in contravention to legal requirements face
      disciplinary action from regulatory boards. Although contact lens prescriptions
      are part of an optometrist's record, the obligation to release prescriptions is
      restricted to 17 states. Optometrists in these states must comply with the
      requirements of state law; in other states, optometrists should establish an
      office policy for the release of contact lens prescriptions, communicate this
      policy to patients at the start of the doctor-patient relationship, and ensure
      that it is properly administered.

PMID- 7812070
TI  - Osteoporosis-2044.
AB  - It is likely that by 2044 biomedical and public health forces will be able to
      control bony fragility to a substantially greater degree than we have succeeded
      in doing today, but that demographic and lifestyle forces already at work will
      offset those gains, perhaps substantially. On the other hand, economic and social
      forces outside of our control will decrease the prevalence of skeletal fragility-
      harshly, I fear--either by strengthening old bones the hard way, or by decreasing
      the numbers of the elderly, or both. The final outcome will be the algebraic sum
      of the effects of these countervailing forces, which is impossible to estimate
      with any assurance. My guess is that osteoporosis will be less of a problem in
      2044, though, unfortunately, for the wrong reasons.

PMID- 7812071
TI  - Morphometric X-ray absorptiometry of the spine: correlation in vivo with
      morphometric radiography. Study of Osteoporotic Fractures Research Group.
AB  - The diagnosis of vertebral fractures has been based on lateral thoracic and
      lumbar spine films and entails the determination of crush, endplate and wedge
      deformities of the vertebral bodies, generally between T4 and L4. Accuracy and
      precision of X-ray based morphometry are limited by geometric distortion and
      other technique-related factors. This paper proposes the use of morphometric X
      ray absorptiometry (MXA) as a method which overcomes many of the limitations of
      morphometric radiography. MXA generates paired anteroposterior and lateral images
      of the spine using a scanning fan beam geometry that significantly reduces
      distortions inherent in the cone beam geometry used in conventional X-rays. Intra
      observer precision of MXA on 41 subjects aged 65 years and older was 1 mm for
      vertebral height assessments and 4.7% for vertebral wedge parameters. Linear
      correlation with vertebral heights and wedge parameters on 32 subjects evaluated
      by both MXA and morphometric radiography demonstrated a root of the mean squared
      error of 2.1-2.4 mm and 7.0%, respectively. Vertebral deformities could be
      identified by MXA. The study documents the feasibility of MXA for the assessment
      of vertebral deformities. However, further investigation is needed to document
      the ability of MXA to diagnose prevalent and incident fractures.

PMID- 7812072
TI  - Effects of calcium supplements on femoral bone mineral density and vertebral
      fracture rate in vitamin-D-replete elderly patients.
AB  - The efficacy of calcium (Ca) in reducing bone loss is debated. In a randomized
      placebo-controlled double-masked study, we investigated the effects of oral Ca
      supplements on femoral shaft (FS), femoral neck (FN) and lumbar spine (LS) bone
      mineral density (BMD), and on the incidence of vertebral fracture in vitamin-D
      replete elderly. Ninety-three healthy subjects (72.1 +/- 0.6 years) were randomly
      allocated to three groups receiving 800 mg/day Ca in two different forms or a
      placebo for 18 months. Sixty-three patients (78.4 +/- 1.0 years) with a recent
      hip fracture were allocated to two groups receiving the two forms of Ca without
      placebo. FS BMD changes in Ca-supplemented non-fractured women were significantly
      different from those in the placebo group (+0.6 +/- 0.5% v -1.2 +/- 0.7%, p <
      0.05). There was no difference in effect between the two forms of Ca. The changes
      of +0.7 +/- 0.8% v -1.7 +/- 1.6% in FN BMD of Ca-supplemented women and the
      placebo group did not reach statistical significance. In fractured patients, FS,
      FN and LS BMD changes were -1.3 +/- 0.8, +0.3 +/- 1.6 and +3.1 +/- 1.2% (p < 0.05
      for the last). The rate of new vertebral fractures was 74.3 and 106.2 fractures
      per 1000 patient-years in Ca-supplemented non-fractured subjects and in the
      placebo group, respectively, and 144.0 in Ca-supplemented fractured patients.
      Thus, oral Ca supplements prevented a femoral BMD decrease and lowered vertebral
      fracture rate in the elderly.

PMID- 7812074
TI  - Relative contribution of vertebral body and posterior arch in female and male
      lumbar spine peak bone mass.
AB  - Peak bone mass (PBM) is an important reference value in the diagnosis of
      osteoporosis. It is usually established by determining the areal bone mineral
      density (BMD in g/cm2) for a given site of the skeleton in young healthy adults.
      This measurement takes into account both the thickness and the integrated mineral
      density of the bone scanned. It should therefore be a major determinant of the
      resistance to mechanical stress. However, in lumbar spine the mean BMD as
      determined by dual-energy either isotopic or X-ray (DXA) absorptiometry in antero
      posterior (ap) view was repeatedly found not to be different between male and
      female young healthy adults despite the greater volume of lumbar vertebral bodies
      in males. A greater contribution of the posterior vertebral arch to areal BMD-ap
      in females than in males could account for such an apparent discrepancy. In order
      to clarify this issue we have determined in 65 (32 male and 33 female) young
      healthy adults aged 20-35 years the relative contribution of the vertebral body
      (VB) and posterior vertebral arch (VA) to BMD and bone mineral content (BMC) of
      L2-3 measured by both antero-posterior and lateral (lat) scanning using DXA. In
      young healthy adults mean BMC in antero-posterior view was found not to be
      significantly different from the total BMC determined by lateral scanning
      including both VB and VA. This allowed us then to calculate the VA BMC by
      substracting VB BMC-lat from BMC-ap.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7812073
TI  - The variable incidence of hip fracture in southern Europe: the MEDOS Study.
AB  - We assessed the incidence of hip fracture and ecological correlates in residents
      of 14 communities in six countries of Southern Europe. Hip fracture cases were
      recorded prospectively in defined catchment areas over a 1-year interval. A
      retrospective questionnaire was used to assess ecological differences between
      communities. During a 1-year period of observation a total of 3629 men and women
      over the age of 50 years were identified with hip fracture from a catchment of 3
      million. In all communities the fracture rate increased exponentially with age.
      There were large and significant differences between centres in the doubling time
      for hip fracture risk with age and in crude and age-standardized rates. Greater
      than 4-fold and 13-fold differences in age-standardized risk were found amongst
      men and women respectively. The lowest rates were observed from Turkey and the
      highest from Seville, Crete and Porto. Fractures were significantly more frequent
      among women than men with the exception of three rural Turkish centres. Indeed,
      in rural Turkey the normal female/male ratio was reserved. Variations in
      incidence between regions were greater than the differences within centres
      between sexes, and there was a close and significant correlation between
      incidence rates for men and those for women in the regions studied. Excess female
      morbidity increased progressively from the age of 50 years but attained a plateau
      after the age of 80 years, suggesting a finite duration of the effect of the
      menopause. The retrospective questionnaire completed by 80% of cases suggested
      that differences in incidence between the communities studied could not be
      explained by differences in gonadal status in women. In both men and women cross
      cultural associations were found with factors related to age or socioeconomic
      prosperity, the majority of which disappeared after adjustment for age. We
      conclude that there are marked and sizeable differences in the incidence rates of
      hip fracture throughout Southern Europe. The reasons for these differences are
      not known but affect both men and women, and are likely to be related to
      lifestyle or genetic factors rather than to differences in endocrine status.

PMID- 7812075
TI  - Mechanisms of rapid bone loss following cardiac transplantation.
AB  - Rapid bone loss after orthoptic cardiac transplantation (OHTX) is a major
      problem; however, the mechanisms are poorly understood. To investigate these
      mechanisms we measured biochemical and hormonal indices of bone turnover serially
      in 25 patients (21 men, 4 women) after OHTX. Serum osteocalcin was reduced
      immediately post-OHTX (2.2 +/- 0.5 ng/ml) but rose significantly by 6 and 12
      months (14.1 +/- 2.5 and 15.7 +/- 2.2 respectively). Bone resorption indices
      (urinary hydroxyproline/creatinine and calcium/creatinine ratios) were increased
      immediately post-OHTX but fell by 6 months. Serum testosterone was reduced in
      males but recovered towards normal values by 6-12 months. Regression analysis
      showed lumbar bone loss was predicted independently by the change in both serum
      osteocalcin and testosterone. The data suggest that bone loss post-OHTX is due to
      a combination of accelerated turnover and hypogonadism.

PMID- 7812076
TI  - Symptomatic fracture incidence in elderly men and women: the Dubbo Osteoporosis
      Epidemiology Study (DOES).
AB  - This longitudinal population-based study documents the incidence of all
      symptomatic fractures from 1989 to 1992 in an elderly, predominantly Caucasian
      population of males and females (> or = 60 years as at 1 January 1989) living in
      the geographically isolated region of the city of Dubbo, NSW, Australia.
      Fractures were ascertained by reviewing reports from all radiology services in
      the region. There were 306 fractures in 271 patients during the study period
      representing 11,401 person-years of observation. In the 60-80 year age group only
      10% of fractures involved the hip, while in the over-80 age group this proportion
      rose to 41%. Incidence of distal forearm, hip and total fractures increased
      exponentially in both sexes with increasing age. Rib fractures were relatively
      common, with incidence rates for rib fractures similar to those for humeral
      fractures. Overall fracture incidence was 2685 per 100,000 person-years (males
      1940 per 100,000 and females 3250 per 100,000). Residual lifetime fracture risk
      in a person aged 60 years with average life expectancy was 29% for males and 56%
      for females. Symptomatic fracture rates with the improved methodology in this
      study were higher than previously reported in both elderly males and females,
      with a marked preponderance of non-hip fractures in the 60-80 year age group.
      These symptomatic fractures have previously been underestimated, if not largely
      ignored, in public health approaches including cost-benefit analyses of
      osteoporosis prevention and treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7812077
TI  - Quality assurance for bone densitometry research studies.

PMID- 7812078
TI  - Hologic's response to Dr Bassett's letter.

PMID- 7812079
TI  - Lunar's response to Dr Bassett's letter.

PMID- 7812080
TI  - Fractures of the femoral neck and arterial disease of the lower limbs.

PMID- 7812081
TI  - Highlights from DataLink: a symposium on the creation of a national database on
      minorities in the biomedical sciences.

PMID- 7812082
TI  - Dietary management of blood pressure.
AB  - Hypertension is a major cause of morbidity and mortality in the United States,
      particularly in the African-American population. Although there have been
      indications since the beginning of this century that blood pressure might be
      influenced by dietary factors, this has been generally ignored, and the mainstay
      of hypertension treatment has been the use of pharmacologic antihypertensives.
      Attention is now being focused, however, on dietary management of hypertension
      because of the high cost of drug therapy, the adverse reactions associated with
      some antihypertensives, and the fact that hypertensives treated only by
      pharmacologic means remain at risk for target-organ damage. The literature is
      replete with evidence that vegetarian and low-sodium dietary patterns are
      associated with lower blood pressure levels. This implies that if many people
      could adopt vegetarian and low-salt dietary habits, the prevalence of
      hypertension would be significantly reduced. However, most people find "unsalted"
      vegetarian diets tasteless and unacceptable. We therefore need to identify the
      macro- and micronutrients (other than sodium) that directly influence blood
      pressure. Several studies indicate that dietary patterns rich in fiber, calcium,
      potassium, and magnesium are favorable for blood pressure control. This review
      highlights some of these findings and emphasizes the need for large clinical
      trials to test blood-pressure-reducing dietary patterns by incorporating the
      aforementioned macro- and micronutrients into socioculturally acceptable and
      palatable menus, especially in the African-American population.

PMID- 7812083
TI  - Effect of insulin-induced hypoglycemia, 2-deoxyglucose-induced glucose cytopenia,
      and hyperglycemia on cardiovascular tone in normal and diabetic rats.
AB  - We studied the metabolic and cardiovascular responses to insulin-induced
      hypoglycemia, 2-deoxyglucose-induced glucose cytopenia, and hyperglycemia in
      normal rats and in rats with streptozocin-induced diabetes. Insulin (2.0 U/kg)
      was infused intravenously into normal and 4-week diabetic rats, and the
      cardiovascular responses were monitored for 90 minutes. Insulin infusion
      decreased plasma glucose and mean arterial pressure by the same relative degree
      in both groups of animals. Heart rate was significantly decreased only in the
      diabetic rats. The injection of 2-deoxyglucose was followed by an increase in
      plasma glucose in both normal and diabetic rats. Heart rate was increased in
      normal rats, and both mean arterial pressure and heart rate decreased in the
      diabetic animals. Hyperglycemia induced by infusion of glucose increased plasma
      glucose and insulin and decreased mean arterial pressure and heart rate in both
      groups of animals. We concluded that acute insulin or insulin-induced
      hypoglycemia decreases cardiovascular tone in normals and, to a significantly
      greater extent, in diabetic rats and that while 2-deoxyglucose-induced glucose
      cytopenia increases cardiovascular tone in normal rats, it elicits a hypotensive
      response in diabetic ones. Glucose-induced hyperglycemia is associated with a
      decrease in cardiovascular tone in both groups of animals.

PMID- 7812084
TI  - Maternal attitudes as predictors of infant feeding decisions.
AB  - To achieve the goal of Healthy People 2000 of increasing the rate and duration of
      breast-feeding in the United States, it is important to determine how maternal
      attitudes influence choice of infant feeding method. This study of postpartum
      women explores the extent to which maternal attitudes concerning process (how the
      baby is fed) and product (what the baby is fed) can predict the method of infant
      feeding during the hospital stay. A cross-sectional analysis of mothers'
      attitudes and infant feeding behavior was conducted. The participants included
      216 mothers of infants less than 48 hours of age. Sociodemographic
      characteristics and maternal attitudes were analyzed to determine their ability
      to predict choice of feeding method. The results of the study indicate that
      maternal attitudes are better predictors of feeding method than are
      sociodemographic factors. These attitudinal variables, reflecting concerns over
      food intake, infant nutrition, and parental role, were most strongly related to
      choice of infant feeding method. The study indicates that maternal attitudes
      concerning the process and product dimensions of infant feeding provide valuable
      information regarding the women most likely to select either breast-feeding or
      formula-feeding. To increase the rate of breast-feeding, interventions should be
      developed that are consonant with positive maternal attitudes concerning the
      process and product dimensions of breast-feeding.

PMID- 7812085
TI  - [Physiologic aging in aqueous humor minute volume of the human eye].
AB  - In 148 healthy volunteers and 75 older patients the physiological aqueous humor
      secretion was calculated during the afternoon hours (13.00 to 20.00 hours) using
      the anterior chamber protocol of Fluorotron Master II (Coherent, Palo Alto, USA).
      Fluorescein eye drops were applied topically to each eye five times, 5 h before
      measurements. Healthy volunteers as well as patients had no history of ocular
      pathology, surgery or laser treatment. Further exclusion criteria were
      hypertension, diabetes, local and systemic drug therapy, neoplasia, kidney or
      liver diseases, contact lens, ocular trauma. Mean age of volunteers was 26.5 +/-
      3.8 years; mean age of patients was 65.5 +/- 10.5 years. The aqueous humor flow
      in healthy volunteers (mean +/- standard deviation) was 2.26 +/- 1.0
      microliters/min and in the older patients 1.91 +/- 1.1 microliters/min.
      Correlation coefficient between right and left eyes in the younger volunteers: r
      = 0.8; in the older patients: r = 0.54. The Mann-Whitney-U-test revealed a
      significant difference comparing mean aqueous humor flow in healthy volunteers
      with the mean aqueous humor flow in older patients (P < 0.01). The results in our
      study underline that the mean aqueous secretion does decrease with age of about
      2.5% per decade. However, to date we do not know whether eyes with primary open
      angle glaucoma or ocular hypertension show such a decrease in aqueous humor flow
      with age or whether there is an autoregulation mechanism in eyes with primary
      open-angle glaucoma that decreases aqueous humor secretion in relation to an
      increase of outflow facility.

PMID- 7812087
TI  - [Argon laser trabeculoplasty in chronic simple glaucoma with visual field defects
      and papillary damage].
AB  - It has been recently demonstrated that the intraocular pressure (IOP) after argon
      laser trabeculoplasty (ALT) in primary open-angle glaucoma rises in the long
      term. The present study analysed the effect of the postoperative rise in IOP in
      36 patients (group A) with glaucomatous optic nerve damage or visual field
      defects. The results were compared with those in 37 patients without such
      glaucomatous damage (group B). The IOP, the cup-disk ratios and the visual fields
      (Goldmann) were retrospectively studied. All patients were under topical glaucoma
      medication. At the end of the follow-up (group A 20.2 +/- 3.39 months, group B
      17.4 +/- 3.59 months), the IOP was uncontrolled in both study groups, and visual
      fields and disc cupping had worsened in both groups. The results indicate that
      ALT should not be considered in patients with optic disc damage or glaucomatous
      visual field defects.

PMID- 7812086
TI  - [Tyndallometry with the laser flare cell meter and biochemical protein
      determination in the aqueous humor of eyes with pseudoexfoliation syndrome].
AB  - Slit-lamp examination and flare measurement in eyes with pseudoexfoliation (PSX)
      syndrome frequently reveal signs of impairment of the blood-aqueous barrier. We
      studied both aqueous flare and aqueous protein concentration in PSX eyes to
      verify and quantify these alterations. PATIENTS: Aqueous flare was measured using
      the Laser Flare-Cell Meter Kowa FC-1000 in 158 normal control eyes (age 56.0 +/-
      12.0 years), in 60 PSX eyes (age 72.5 +/- 9.4 years), and in 84 eyes with primary
      chronic open-angle glaucoma (PCOAG) (age 56.3 +/- 12.4 years). Total aqueous
      protein concentration was determined biochemically in 12 "normal" control eyes
      with senile cataracts (age 57.6 +/- 20.4 years), in 27 PSX eyes (age 72.6 +/- 9.1
      years), and in 25 PCOAG eyes (age 63.3 +/- 13.5 years). After the primary aqueous
      humor was aspirated during cataract extraction or trabeculectomy, a modified BCA
      Peirce method was employed. RESULTS: In PSX eyes, both aqueous flare (12.3 +/-
      8.2 photon counts/ms) and aqueous protein concentration (0.42 +/- 0.16 mg/ml
      total protein) were significantly increased in comparison with normal control
      eyes (4.3 +/- 1.1 photon counts/ms and 0.22 +/- 0.08 mg/ml) and with PCOAG eyes
      (4.7 +/- 1.6 photon counts/ms and 0.26 +/- 0.09 mg/ml) (P < 0.0001). Differences
      between normal control eyes and PCOAG eyes were not significant (P > 0.05). There
      was a high correlation between aqueous flare measurements and aqueous protein
      concentration in eyes with PSX (y = 0.27x + 0.29, r = 0.65, P = 0.0006, n = 24).
      CONCLUSIONS: Our results indicate that impairment of the blood-aqueous barrier
      with an increase in aqueous protein concentration is a feature of PSX and may be
      quantified both by flare measurement and biochemical protein determination. These
      alterations should be considered in the pharmacological and surgical treatment of
      PSX eyes.

PMID- 7812088
TI  - [Controlled trabeculectomy and incidence of postoperative choroidal detachment].
AB  - In this study the authors report their experience with titrated trabeculectomy.
      It is performed as follows: tight scleral flap trabeculectomy, five or more 10/0
      nylon sutures, argon laser lysis of one or more sutures (depending on the eye's
      postoperative condition) by means of the Hoskins lens. The aim of this technique,
      performed by the authors for 3 years, is to decrease atalamia and choroidal
      detachment. Results obtained in 70 eyes of 62 patients with chronic open-angle
      glaucoma are compared by means of statistical analysis with those in 70 eyes of
      66 patients operated on by means of the traditional technique. The incidence of
      choroidal detachment is significantly reduced (P < 0.001). There is no important
      difference in ocular pressure and visual acuity. In conclusion, this technique is
      very useful in controlling and titrating the filtration rate, avoiding an
      excessive lowering of IOP after trabeculectomy and decreasing the complications.

PMID- 7812089
TI  - [Experiences with sclerostomy with the Holmium laser].
AB  - The THC-YAG laser (holmium laser) war used to perform ab externo sclerostomies in
      patients affected by various types of glaucoma. This approach was employed in 48
      eyes with diagnoses of medically uncontrolled chronic open angle glaucoma,
      plateau iris or neovascular glaucoma. Post-operatively, 5-FU was injected. At the
      tend of the follow-up (mean 10.22 +/- 3.4 months), in 25 eyes (52.1%) the IOP was
      under control without medical therapy. In 12 eyes (25.0%) it was necessary to use
      antiglaucomatous topical therapy, and in 11 eyes (22.9%) the IOP was uncontrolled
      despite therapy. The authors stress the importance of a correct pharmacological
      protocol before and after operation and describe the surgical technique. They
      confirm the validity of this approach, owing to its minical invasiveness, the
      possibility of repeating the procedure, and the low complication rate.

PMID- 7812090
TI  - [Perfusion time of the central retinal artery in normal pressure glaucoma.
      Initial results].
AB  - A possible explanation for the progressive visual field defects in normal tension
      glaucoma is reduced ocular blood flow. We have tried to answer this question
      using fluorescence perfusion scintigraphy that measures the circulation times
      between the subclavian vein, carotid artery, central retinal artery and central
      retinal vein. PATIENTS: Eight normal subjects and eight age- and sex-matched
      normal tension glaucoma patients were compared. Inclusion criteria for NTG
      patients were an IOP below 23 mmHg, glaucomatous visual field defects,
      glaucomatous disk cupping, normal chamber angle and no neurologic deficits. The
      subclavian carotid time, the carotid retina time and the mean retinal perfusion
      time of the intravenously injected radioactive fluorescein bolus were measured
      using digitized scanning laser angiography and technetium scintigraphy. RESULTS:
      Subclavian carotid time and mean retinal perfusion time were not significantly
      different between groups, whereas the carotid retina time was 1.6 s (min = 0.8,
      max = 2.6) in normals and 3.3 (min = 2.6, max = 4.2) in normal tension glaucoma.
      This difference was highly significant (P < 0.001). CONCLUSIONS: The delay of the
      carotid retina circulation time in normal tension glaucoma patients may reflect a
      reduced blood flow velocity in the internal carotid artery, the ophthalmic artery
      and the central retinal artery. The subclavia carotid time and ultrasound
      investigation of the carotid artery were normal. This suggests that the delayed
      carotid retina time is an indicator of reduced blood flow velocity in ophthalmic
      and mainly central retinal artery. The good discrimination between normal
      subjects and NTG patients must be confirmed in a larger group of patients.

PMID- 7812091
TI  - [Single dose administration in therapy of glaucoma. Comparison of costs with
      multiple dose].
AB  - Preservatives in antiglaucomatous agents can irritate the conjunctiva and may
      lead to allergic reactions. Preservative-free single-dose applications of
      glaucoma medications have increasingly become available. We analysed the therapy
      costs for single-dose containers per eye and per year and compared them with
      those for multidose containers. The data were calculated from prices taken from
      the German pharmacy index, applications per day and number of drops in the
      container. The drop volume ranged from 34.3 microliters to 48.0 microliters for
      single-dose containers and from 29.2 microliters to 40.0 microliters for
      multidose containers. The annual cost of therapy with beta-adrenergic antagonist
      preparations was DM 42.59-DM 80.78 for multidose containers and DM 162.73-DM
      242.42 for single-dose containers. The cost of therapy with philocarpine was DM
      21.55 but DM 233.92 for single-dose containers. The cost of combination therapy
      with beta-adrenergic antagonist preparations and pilocarpine ranged from DM 67.92
      to DM 214.33 for multidose containers and from DM 408.15 to DM 428.95 using
      single-dose containers. Therapy with preparations in single-dose containers is
      more expensive than with multidose containers (+161 to +1169%). Preparations in
      single-dose containers without preservatives can have advantages, but the higher
      costs necessitate careful selection of the patients.

PMID- 7812093
TI  - [Transforming growth factors beta 1 and 2 inhibit proliferation of limbus and
      corneal epithelium].
AB  - The role of the various isoforms of transforming growth factor-beta (TGF-beta)
      concerning the regulation of proliferation, differentiation and wound healing of
      the corneal epithelium is controversial. We investigated various concentrations
      of TGF-beta 1 and 2 in a serum-free, defined clonal growth assay concerning the
      proliferation of limbal and peripheral corneal epithelium. Concentrations between
      0.05 and 5.0 ng/ml of either TGF-beta 1 or 2 caused a significant, dose-dependent
      decrease of both colony formation and colony proliferation in limbal and
      peripheral corneal epithelial cultures. These results suggest a physiological
      role for TGF-beta as a negative growth regulator targeting primarily the
      transient amplifying cells of the limbal and corneal epithelium.

PMID- 7812092
TI  - [T-cell-induced prevention of HSV-1 keratitis by immunization with the synthetic
      peptide of glycoprotein D].
AB  - C.AL-20 mice susceptible to herpes simplex virus (HSV) were protected against HSV
      keratitis (HSK) and encephalitis by subcutaneous immunization with synthetic
      peptide corresponding to the N-terminal amino acid residues 5-23 of HSV
      glycoprotein D, which is a dominant immunogen of HSV-1. Protection against HSV
      was related to a potent humoral anti-HSV response. FACScan analysis revealed that
      CD4+V beta 8(1.2)+ cells in the spleen were markedly decreased 2 days after HSV
      challenge, and CD8+ cells were increased. Numerous CD4+ and V beta 8(1.2)+ cells
      were found in the corneal tissue from HSV-infected sham-immunized mice; no such
      cells were seen in gD(5-23) immunized mice. No cytotoxic cells were detected in
      the corneas or spleens of gD(5-23) immunized mice, and these mice had decreased
      DTH responses. Protection against HSV through immunization with gD(5-23) involves
      humoral and cellular immune mechanisms. CD4+V beta 8(1.2)+ maybe critical in
      mediating the pathology of HSK. CD8+ cells may be protective by non-cytotoxic
      mechanisms. Our results suggest that gD peptides may be potent as vaccines
      against HSV.

PMID- 7812094
TI  - [Viability of corneal endothelium after long-term storage at +4 degrees C in
      Optisol].
AB  - For successful corneal transplantation endothelial cell function of at least 50%
      is considered necessary. Corneal grafts are often evaluated by morphological
      criteria, such as endothelial cell size or density. Donor corneas with a storage
      time longer than 10 days are usually excluded from transplantation. The viability
      of the endothelium of 35 human donor corneas was evaluated after storage for up
      to 27 days at +4 degrees C in Optisol storage medium by using the Janus green
      photometry technique. The results were compared with the endothelial cell density
      counted. We demonstrated that the human corneal endothelium remains
      satisfactorily viable (minimum 68% viable cells) for a period of at least 27 days
      and that morphological changes do not sufficiently reflect the functional
      intactness of the cornea. Morphological irregularities should be interpreted as a
      form of compensation by a viable endothelial cell layer.

PMID- 7812095
TI  - [Problems in perforating keratoplasty with large diameter].
AB  - The follow-up of 52 perforating corneal grafts with a diameter of more than 9 mm
      is presented. The indications for surgery in this series were different from
      those in a control group. In the 3-year follow-up time most transplants were
      clear and had a good final visual outcome. Secondary glaucomas were not
      significant, but a high endothelial cell density decrease could be demonstrated.

PMID- 7812096
TI  - [Corneal reinnervation after lamellar keratoplasty in comparison with
      epikeratophakia and photorefractive keratectomy].
AB  - Corneal sensitivity was examined with the Draeger aesthesiometer in 8 patients
      after lamellar keratoplasty, 7 patients after epikeratophakia and 82 patients
      after photorefractive keratectomy. We examined 9 different points in each cornea.
      The corneal sensitivity of patients after lamellar keratoplasty was normal 1 year
      after operation. A correlation with the depth of the lamellar dissection was
      demonstrated. Patients with lamellar keratoplasty with pterygium showed a
      sensitivity decrease in the nasal parts of the lenticule even after one year.
      Three years after epikeratophakia the corneal center was still not sensitive.
      After photorefractive keratectomy of more than 10 D, corneal hyposensitivity was
      shown even 2 years after operation.

PMID- 7812097
TI  - [Experimental studies on the effect of the Er:glass and Cr:Tm:Ho:YAG laser in
      thermokeratoplasty].
AB  - So far the dose-effect ratio of the Holmium laser (wavelength 2.12 microns) and
      the erbium laser (1.54 microns) for laser thermokeratoplasty (LTK) are not
      defined in detail. Our study was designed not only to compare the erbium contact
      and the holmium non-contact applications but also to throw light on the influence
      of different geometrical application patterns, pulse energies, pulses per
      coagulation site and repetition rates under experimental conditions. Enucleated
      sheep and pig eyes were used 2-6 h post mortem, pressurized to 25 mmHg and
      moisturized with saline solution. Before and after LTK, pachymetry and
      keratometry were performed. Some specimens were prepared for light and scanning
      microscopy. The coagulation threshold for the erbium laser in a contact mode with
      a 200-microns fibre was 25 J/cm2 (ca. 8 mJ/pulse) and for the holmium laser 8
      J/cm2 (ca. 2.5 mJ/pulse). The erbium laser was used in a single shot per spot
      mode, the holmium laser in repeated pulse per spot mode. With the single shot per
      spot mode, we were able to induce a promising hyperopic shift of up to -3.47 +/-
      0.61 D, while myopic changes could only be induced up to +1.89 +/- 0.74 D. Higher
      changes of up to +8.27 +/- 1.3 D could be achieved by means of repeated pulses
      per spot (20 pulses, 45 mJ, 10 Hz). Our experiments showed an obvious increase of
      dioptric changes when using a higher repetition rate while pulse energy and
      number were kept constant.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7812098
TI  - [15 months photorefractive keratectomy at the Munster University Eye Clinic].
AB  - We performed a photorefractive keratectomy (PRK) in 51 myopic eyes of 34
      patients. Cortisone-responders were excluded. All patients were unable to
      tolerate contact lenses. The intended correction was between -1.75 and -7.0 D.
      None of the patients demonstrated a decrease in visual acuity at its highest
      level of correction. The maximum haze was +1. No eye had to be reoperated upon.
      Nine months after PRK, the maximum deviation from the intended correction was 2 D
      in a -6.5 D correction. After 12 months, however, we found a regression of 2 D
      without signs of keratoconus or increase of haze in 2 patients.

PMID- 7812099
TI  - [Moist ablation of the corneal surface with the Er:YAG laser. Results of
      optimizing ablation].
AB  - The Er:YAG laser, emitting light at 2.94 microns, may be an alternative to the
      193 nm excimer laser for photorefractive keratectomy. Compared to the excimer
      laser, the ablation rate is very high. Surface roughness is also more pronounced
      than for the excimer laser. Using a precorneal liquid film, these two factors can
      be reduced, as shown in ablation experiments performed on porcine corneas.
      Thermal damage of the remaining corneal tissue is another side effect. There is
      no significant decrease in the amount of thermal damage with this new technique,-
      not even when the pulse length is reduced.

PMID- 7812100
TI  - [Intrastromal refractive corneal surgery with pico-second Nd:YAG laser pulses].
AB  - Intrastromal laser surgery with picosecond pulses aims to achieve refractive
      changes of the cornea without damaging the epithelium, Bowman's membrane, or the
      endothelium. For that, a tissue layer with well-defined thickness has to be
      evaporated by creating laser plasmas within the corneal stroma. We investigated
      the plasma formation and the plasma-induced shock wave emission and bubble
      generation (cavitation) in the cornea, as well as the tissue effects and the
      range for endothelial damage. The laser light source used was an Nd:YAG laser
      emitting pulses with a duration of 30 ps at a repetition rate of 10 Hz.
      Intrastromal plasma formation and cavitation were investigated in sheep eyes in
      vitro by means of time-resolved macro-photography with 20 ns exposure time.
      Photographs were taken at various delay times (3 microseconds-2 min) after the
      release of the Nd:YAG laser pulse. The morphology of the laser effects and the
      incidence of endothelial damage was investigated by light-microscopic inspection
      of histological cross sections of the irradiated corneas. The minimal plasma size
      at energies close to the breakdown threshold was about 40 microns. Using a laser
      effects could be created without causing microscopically detectable damage to the
      epithelium, endothelium, or Bowman's membrane. To avoid damage, the distance
      between endothelium and laser focus had to be larger than 150 microns. Shock wave
      induced tissue damage was not observed, although the maximum shock wave pressure
      was up to 13 kbar. The laser-generated intrastromal cavities are at least 10
      times larger than the plasma volume.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7812101
TI  - [HIV-1 and tears. Results of virus isolation and polymerase chain reaction
      (PCR)].
AB  - Beside the threat of infection via HIV-containing blood, the ophthalmologist is
      especially interested in the possibility of HIV infection via the tears of HIV
      positive persons. In a first step, we tried to isolate HIV-1 from the peripheral
      blood lymphocytes (PBL) of 50 HIV-1-antibody-positive persons in different stages
      of disease and to detect reverse transcriptase (RT) and p24 antigen (p24-Ag) in
      the supernatant. Simultaneously we carried out the same tests on tears of these
      patients. In 10 persons tears were collected using Schirmer strips, in 40 persons
      by means of microcapillaries. In a second step 10 sample pairs (PBL and tears)
      were tested with the polymerase chain reaction to detect proviral sequences of
      HIV-1 (gag, pol, env). In the first step it was not possible to isolate HIV-1
      from tears, nor was it possible to detect RT or p24-Ag from the supernatant. In
      contrast, this was successful in 32 of the 50 examined cases for the PBL. In the
      second step, it was possible to detect gag, pol and env in all 10 PBL samples,
      while gag and pol could be detected only in one tear sample and env not at all.
      Our results show that the tears of HIV-positive persons contain extremely low
      quantities of tissue-infectious units of HIV. In addition, proviral sequences
      seem to occur in much lower frequency in tears than in PBL. Infection with HIV
      via tears therefore appears very unlikely. These findings make it possible to
      assign tears a place in a semiquantitative ranking of different body fluids by
      HIV-1 concentration.

PMID- 7812102
TI  - [Ophthalmologic manifestations in early and late stages of AIDS].
AB  - In a prospective study of 101 patients with HIV infection and a medium CD4
      lymphocyte cell count of 350 x 10(6)/l and a retrospective study of the records
      of 79 AIDS patients, we compared the first ocular symptoms in HIV-infected
      patients to the CD4 count. In Walter-Reed stages 2-4 (n = 101) we found sicca
      syndrome in 9.2%, in 52% lens opacities in the cortex and only in less than 1%
      HIV-related angiopathy of the retina. In Walter Reed stages 5-6 (n = 79), 26% of
      the AIDS patients developed CMV retinitis, 33% HIV angiopathy of the retina and
      only 1% retinal toxoplasmosis. The average CD4 lymphocyte cell count was never
      better than 100 x 10(6). Lens opacities in HIV-infected patients could be an
      early ophthalmological symptom of HIV infection.

PMID- 7812103
TI  - [Ocular chlamydia infections in Munsterland. A clinical study of 409 patients].
AB  - We evaluated demographic data, McCoy cell cultures from conjunctival smears and
      chlamydia-specific IgG and IgA serum antibody titers in 409 patients (194 men and
      212 women) suffering from (kerato)conjunctivitis of presumed bacterial etiology
      in 1988-1992. Overall, 105 patients were positive in culture and/or serology
      tests (78 in McCoy cell cultures, 45 in serology tests). In 33 patients (31%)
      corneal involvement was epithelial (5), subepithelial (13), phlyctenular (7)
      and/or took the form of pannus vasculosus (12). The incidence and severity of
      corneal signs correlated with the duration of the (kerato)conjunctivitis.
      Nasolacrimal duct complications were documented in 16 patients with a duration of
      illness exceeding 6 months. Some 33% of cases were recorded in May and June, a
      further 26% from November to January. The age groups primarily affected were:
      females 20-30 years (25%), males 30-40 years (25%). The highest number of new
      cases was registered in 1990.

PMID- 7812104
TI  - [No detection of mycoplasma in 205 conjunctival swabs].
AB  - Mycoplasma is known to cause pulmonary and urogenital infections in humans. A
      pathogenicity for the human eye never has been assessed, although they have been
      observed in the peripheral eye in a few cases of acute and non-specific
      conjunctivitis, in patients with Reiter's disease and in newborns. Due to the
      absence of cell walls, mycoplasma is only sensitive to a few antibiotics.
      Therefore, we presume that mycoplasma has a role in non-specific and chronic
      conjunctivitis. It is conceivable that in HIV-positive patients the risk of
      opportunistic colonization of the conjunctiva by mycoplasma is increased.
      PATIENTS AND METHODS. Between January and December 1992, 205 conjunctival swabs
      of 151 patients were prospectively analyzed for mycoplasma. The group contained
      51 HIV-infected patients (94 swabs). A total of 85 swabs were from non-irritated
      eyes and the remaining (120) from peripherally inflamed eyes, mainly diagnosed as
      non-specific or chronic conjunctivitis (75 swabs). Specimen were obtained from
      the inferior fornix conjunctivae by use of a moistened cotton swab, which was
      directly immersed in culture broth. For subsequent culture, we used a liquid and
      a solid mycoplasma medium to differentiate Mycoplasma hominis, Mycoplasma
      fermentans and Ureaplasma urealyticum. In 77 swabs, a second sample was taken,
      which was investigated at the Institute for Poultry Diseases of the Ludwig
      Maximilians University, Munich. OUTCOME. None of 205 swabs, including the 77
      samples tested in parallel, gave positive results for mycoplasma. Six cases were
      positive for bacteria and five cases for fungi. CONCLUSION. In adult patients at
      the Munich University Eye Hospital with either non-irritated eyes or non-specific
      and chronic conjunctivitis, no mycoplasma could be detected. With regard to HIV
      infection, there is no indication that mycoplasma plays a role in opportunistic
      infections of the conjunctiva.

PMID- 7812105
TI  - [Area of contact of the artificial lens and posterior capsule. Systematic study
      of various haptic parameters].
AB  - New techniques in cataract surgery, namely the small and tunnel incisions, have
      led to intraocular lens (IOL) designs with haptics angulated anteriorly as low as
      0 degrees. Clinical and animal studies strongly support the inhibitory influence
      of contact between the optic and the posterior capsule on the formation of
      posterior capsular opacification. Human cadaver eyes were used to examine the
      effect of different haptic angulations (1 degree, 5 degrees, 10 degrees, 15
      degrees), different haptic diameters (11.5 mm, 12.0 mm, 12.5 mm), and different
      optic diameters (5.0 mm, 6.0 mm) on the area of contact between optic and
      posterior capsule. Exciting fluorescein with a Wood light visualized the space
      between the IOL and the posterior capsule. Only IOLs with haptics bent forward at
      more than 10 degrees could achieve contact between IOL and posterior capsule. The
      haptic and optic diameters had only a limited effect.

PMID- 7812106
TI  - [Measuring corneal sensitivity with the air aesthesiometer in comparison with the
      Draeger electromagnetic air aesthesiometer].
AB  - A new air aesthesiometer developed by S. Weinstein was tested with an anemometer
      device. It could be shown that the air stream is not linear. The normal
      sensitivity threshold pattern was measured in 271 probands varying in age from 10
      to 98 years. In a comparative study we measured the corneal sensitivity of 20
      patients after penetrating keratoplasty with the air aesthesiometer and the
      Draeger electromechanical aesthesiometer. Because of the aerodynamic broadening
      of the airstream it was not possible to measure corneal sensitivity at the
      transplant periphery or host cornea with the new device, while we could
      demonstrate corneal nerve fibre degeneration at the host cornea or regeneration
      of the transplant with the electromechanical aesthesiometer.

PMID- 7812107
TI  - [Laser therapy of eyelid and conjunctival tumors, especially in AIDS patients].
AB  - We treated patients with Kaposi's sarcoma of the lid or conjunctiva, molluscum
      contagiosum and papilloma of the lid with dye laser photocoagulation. This
      therapeutic device is extremely efficient as the chosen wavelength of 577 nm is
      absorbed selectively by haemoglobin. Since Kaposi's sarcoma is a haemoglobin
      containing tumour composed of endothelial cells and papilloma is a benign tumour
      composed of connective tissue and branching vessels, dye laser photocoagulation
      causes selective damage to abnormal vessels and surrounding connective tissue.
      After local anaesthesia a small incision was made at the margin of the lesion
      five patients each with papilloma and with molluscum contagiosum. In six patients
      with Kaposi's sarcoma no incision had to be done. Starting from the incision or
      the margin of the Kaposi's sarcoma 50-100 shots of 0.3-0.5 mm diameter and 1 s
      duration were applied until the lesion was completely gone. We used a dye laser
      with 577 nm wavelength and 1 W energy. In patients with papilloma, the tumour
      basis was coagulated and the tumour itself underwent histological examination.
      There was a marked decrease of the size of the lesion or even complete
      disappearance. Since Kaposi's sarcoma in AIDS patients can be relatively fast
      growing, resulting in cosmetically irritating manifestations and, rarely,
      haemorrhages, treatment may become necessary. AIDS patients with molluscum
      contagiosum may also benefit from treatment, as spreading of DNA virus particles
      may result in viral follicular conjunctivitis. Dye laser photocoagulation,
      however, cannot protect against relapse.

PMID- 7812108
TI  - [Reversible translimbal suture fixation of the ciliary body in treatment of
      ocular persistent hypotonia after surgical cyclodialysis].
AB  - After surgical or traumatical cyclodialysis dangerous hypotony can occur. In
      cases with peripheral anterior synechia the fixation of the ciliary body by
      reversible suture can bring about the desired pressure rise. PATIENTS: In nine
      eyes with persistent ocular hypotony after cyclodialysis 13 ciliary body
      fixations were performed. RESULTS: In four eyes the operation was successful. In
      two eyes a second operation was necessary. In two cases there was a high
      postoperative pressure rise. Cutting of the sutures led to a sudden decrease in
      pressure. In these eyes a second operation with slightly different fixation
      position was successful. One eye remained hypotonic. CONCLUSIONS: This operative
      technique entail only slight risk while having good results in patients with
      aphakia and extensive peripheral anterior synechia. During the early
      postoperative periods there is the opportunity to reverse the operative effect.

PMID- 7812109
TI  - [Self tonometry during the German 1993 Spacelab D2 mission].
AB  - Microgravity during space missions leads to a fluid shift from the lower to the
      upper parts of the body that also affects the intraocular pressure. In the early
      phase after reaching microgravity there is an intraocular pressure peak. In order
      to analyse the potential health risks for astronauts, a self-tonometer was
      developed to examine the early phase of microgravity. During the German-Russian
      MIR mission the equipment was tested for the first time in space. As one result
      we found an initial pressure increase of 92% compared to the baseline data
      values. In order to obtain more detailed information on the intraocular pressure
      alterations in space, similar equipment was used during the 10-day German
      Spacelab D2 mission. Two German scientists and one American astronaut obtained
      self-tonometric pressure profiles on 6 mission days (44 pressure values
      determined out of 144 measurements). The initial peak values 15 min after
      entering microgravity revealed pressure increase of 114% compared to the baseline
      data (average pressure: right eye 10.0 mmHg, left eye 9.9 mmHg; peak values:
      right eye 22.6 mmHg, left eye 22.2 mmHg). Pressure values exceeding the baseline
      data by more than 50% were registered up to the 3rd mission day. As to circadian
      rhythm, there was no difference between inflight data and baseline data before
      and after the mission.

PMID- 7812110
TI  - [Tumors of the orbits].

PMID- 7812111
TI  - Potentiation of iron accumulation in cardiac myocytes during the treatment of
      iron overload in gerbils with the hydroxypyridinone iron chelator CP94.
AB  - Gerbils administered iron dextran are the only animal species which have been
      shown to develop hemochromatosis of the liver and heart in the same manner as
      transfusion dependent homozygous thalassemics. The iron chelating
      hydroxypyridinone, CP94, has been administered prophylactically to iron
      overloaded gerbils in a dosing regime which favors the formation of bidentate
      chelated iron, to examine the possibility of additional toxicity being caused to
      the liver and heart by the bidentate chelated iron complex. Hepatic iron
      accumulation was inhibited by CP94 administration for up to 6 weeks, but not
      after 20 weeks. Iron accumulation in the heart was increased significantly after
      6 and 20 weeks of chelator treatment. Pathological changes in both organs were
      markedly more severe after 20 weeks in chelator treated animals. There was a
      higher incidence of cardiofibrosis and more extensive liver fibrosis in iron
      overloaded, chelator treated animals after 20 weeks.

PMID- 7812112
TI  - Characteristic features of the heterologous functional synthesis in Escherichia
      coli of a 2[4Fe-4S] ferredoxin.
AB  - Different strategies have been used to express synthetic genes all encoding
      Clostridium pasteurianum 2[4Fe-4S] ferredoxin (Fd) in Escherichia coli. The
      polypeptide can be produced as the C-terminal addition to a hybrid Cro::Protein A
      fusion protein lacking the metallic centers. The incorporation of the [4Fe-4S]
      clusters into the cleaved apoFd cannot be carried out in the same conditions as
      those affording holoFd from purified C. pasteurianum apoFd. In contrast, fully
      functional Fds can be produced from non-fused synthetic genes under the
      dependence of strong promoters. The yields of recombinant Fd, although sufficient
      to purify significant quantities of protein, are limited by the very short half
      life of the 2[4Fe-4S] Fd in E. coli, irrespective of the expression system used.
      These features are characteristic of 2[4Fe-4S] Fds when compared with the far
      more stable recombinant rubredoxin, and probably other small iron-sulfur proteins
      which have already been produced in high yields. The reasons for the high
      turnover of 2[4Fe-4S] Fds are discussed.

PMID- 7812113
TI  - Detection and differentiation of microbial siderophores by isoelectric focusing
      and chrome azurol S overlay.
AB  - Siderophores are microbial, low molecular weight iron-chelating compounds.
      Fluorescent Pseudomonads produce different, strain-specific fluorescent
      siderophores (pyoverdines) as well as non-fluorescent siderophores in response to
      low iron conditions. We present an isoelectric focusing method applicable to
      unpurified as well as to purified pyoverdine samples where the fluorescent
      siderophores are visualized under UV illumination. Siderophores from different
      Pseudomonas sp., amongst which are P. aeruginosa, P. fluorescens and P. putida,
      including egg yolk, rhizospheric and clinical isolates as well as some derived
      Tn5 mutants were separated by this technique. Different patterns could be
      observed for strains known to produce different siderophores. The application of
      the chrome azurol S assay as a gel overlay further allows immediate detection of
      non-fluorescent siderophores or possibly degradation products with residual
      siderophore activity. The method was also applied to other microbial siderophores
      such as deferrioxamine B.

PMID- 7812114
TI  - Site-directed mutagenesis of the ferric uptake regulation gene of Escherichia
      coli.
AB  - The 12 histidine and four cysteine residues of the Fur repressor of Escherichia
      coli were changed, respectively, to leucine and serine by site-directed
      mutagenesis of the fur gene. The affects of these mutations were measured in vivo
      by ligation of the mutated genes to a wild-type fur promoter followed by
      measurement of the ability of these plasmids to regulate expression of a lacZ
      fusion in the aerobactin operon. In vitro affects were assayed by insertion of
      the mutated genes in the expression vector pMON2064 attended by isolation of the
      altered Fur proteins and appraisal of their capacity to bind to operator DNA. The
      results suggest that cysteine residues at positions 92 and 95 are important for
      the activity of the Fur protein.

PMID- 7812116
TI  - Magnesium contents of leukemic lymphocytes.
AB  - In this study, magnesium concentrations were measured in lymphocytes from
      patients with acute myeloblastic leukemia (AML), chronic megalositer leukemia
      (KML) and acute lymphoblastic leukemia (ALL) before and after chemotherapy
      management, and results were compared with those of control subjects. Magnesium
      concentrations were higher in the patient groups compared with control values.
      However, no meaningful differences were found among magnesium concentrations of
      the patient groups themselves. Similarly, no statistically meaningful differences
      were found between lymphocyte magnesium concentrations before and after
      chemotherapy management in the patient groups. In the inter-correlation analysis,
      we observed no correlations between pre- and post-magnesium concentrations in
      patients' lymphocytes. It has been suggested that magnesium concentrations of
      leukemic lymphocytes might increase due to the high ATP requirement of the
      leukemic cells since magnesium is known to play an important part as a cofactor
      in most of the energy-producing reactions.

PMID- 7812117
TI  - Simultaneous determination of a mixture of organophosphorus and carbamate
      pesticides by high performance liquid chromatography.
AB  - A simple HPLC procedure has been developed for the simultaneous determination of
      a mixture of standard carbaryl, carbofuran, carbendazim, dimethoate, malathion
      and methyl parathion from a spiked agricultural soil sample. The pesticide
      mixture has been extracted using methanol-water. A concave gradient elution with
      acetonitrile-phosphate buffer for 15 min followed by linear elution for 5 min,
      using a wavelength of 224 nm for detection, has been found to resolve the mixture
      efficiently.

PMID- 7812118
TI  - Simultaneous determination of antidepressant drugs and metabolites by HPLC.
      Design and validation of a simple and reliable analytical procedure.
AB  - An analytical procedure suitable for routine use has been developed and validated
      for the simultaneous separation and quantification of most of the antidepressant
      drugs (bicyclic, tricyclic and tetracyclic) and their metabolites in human serum
      by reversed-phase high performance liquid chromatography with ultraviolet
      detection. The method has good sensitivity and specificity, without the need for
      long and complex extraction procedures. The results obtained with three different
      analytical columns were compared and an improvement in specificity by selection
      of column and detection wavelength used was achieved.

PMID- 7812115
TI  - Uptake of selenite, selenomethionine and selenate by brush border membrane
      vesicles isolated from rat small intestine.
AB  - The uptake of selenite, selenate and selenomethionine (SeMet) was performed with
      brush border membrane vesicles (BBMV) prepared from rats fed selenium-deficient
      and supplemented diets. At equilibrium (60 min), the uptake of 75Se from
      [75Se]selenite ranged from 16.5 to 18.9 nmol mg-1 protein. There was a
      curvilinear relationship in the uptake of selenite over a concentration range of
      10-1000 microM. About 2 nmol mg-1 protein was obtained with selenomethionine
      (SeMet) which occurred between 90 and 180 s. In contrast to selenite, there was a
      linear relationship in the initial uptake of SeMet over a concentration range of
      10-1000 microM. The uptake of selenate was approximately 50-fold lower than
      selenite, reaching 350 pmol mg-1 protein. Dietary selenium level had no effect on
      the rate of 75Se accumulation by BBMV. Dramatic differences are found in the
      uptake and binding of selenium by BBMV incubated with different selenocompounds.

PMID- 7812119
TI  - Continuous beds. Their applicability for immobilization of proteins.
AB  - An epoxy-activated continuous bed can be prepared for immobilization of proteins
      in a simple, rapid, and cost-effective way. The concentration of epoxy groups on
      the continuous bed was as high as 600 mumol/mL compressed bed (compression of the
      bed decreases the peak broadening). Human transferrin, human serum albumin and
      particularly urease were employed as model proteins. The immobilization of urease
      was virtually completed within 1 h in 1 M potassium phosphate, pH 7.4. The
      binding capacity was 97 mg of urease/mL compressed bed. This bed is of clinical
      interest, since it is inexpensive to prepare and permits reproducible enzymatic
      determination of urea in serum and urine (the chromatographic step is finished
      within 1-2 min).

PMID- 7812121
TI  - Use of capillary electrophoresis for thalassaemia screening.
AB  - This paper describes the use of high-performance capillary electrophoresis (HPCE)
      for screening of thalassaemias. Preparation of globin was performed by adding 1
      mL of haemolysate to 20 volumes of cold acidified acetone. Separation of globins
      was accomplished in a 25 mM disodium phosphate buffer at pH 11.8 using an
      uncoated capillary column of 50 cm x 75 microns (i.d.). Distinct peaks of alpha,
      beta and gamma were resolved within 6 min. The coefficient of variations for
      within-day and between-day runs were 4.7% and 6.37%, respectively. Using this
      simple and rapid procedure up to 30 specimens could be analysed in a single day.
      This method appears to be reliable and can be used for mass screening of various
      haemoglobinopathies.

PMID- 7812120
TI  - Enantiospecific determination of ibuprofen in rat plasma using chiral
      fluorescence derivatization reagent, (-)-2-[4-(1-aminoethyl)phenyl]-6-
      methoxybenzoxazole.
AB  - A highly sensitive and reversed-phase high-performance liquid chromatographic
      method for the determination of the enantiomeric composition of ibuprofen in rat
      plasma is described. The method is based on the resolution of the diastereomeric
      amides formed on reaction of the ibuprofen enantiomers with (-)-2-[4-(1
      aminoethyl)phenyl]-6-methoxybenzoxazole ((-)-APMB) in the presence of 2,2'
      dipyridyl disulphide (DPDS) and triphenylphosphine (TPP) in dichloromethane. The
      reaction mixture was allowed to stand at room temperature for 5 min, and the
      reaction was completed by evaporation with a stream of nitrogen at 40 degrees C.
      The minimum quantifiable concentrations were 0.2 microgram/mL and 0.4
      microgram/mL for S-ibuprofen and R-ibuprofen, respectively, in a 10 microL
      injection volume. The method was applied to the determination of enantiomeric
      ibuprofen in plasma after oral administration to rats.

PMID- 7812122
TI  - Gas chromatography-mass spectrometry determination of etodolac in human plasma
      following single epicutaneous administration.
AB  - A highly sensitive gas chromatographic-mass spectrometric method for the
      determination of etodolac acid, as methyl ester, in plasma was developed. The
      feasibility and specificity of the method was ascertained monitoring the
      concentration levels in plasma samples collected from 12 male healthy volunteers
      given epicutaneously 5 g of 10% etodolac gel formulation.

PMID- 7812123
TI  - Carbonic anhydrase-immobilized precolumn for selective on-line sample
      pretreatment in high-performance liquid chromatographic determination of certain
      sulphonamide drugs.
AB  - Carbonic anhydrase (CA)-immobilized aminopropyl silica precolumn was developed
      for direct injection determination of certain sulphonamide drugs in biological
      fluids by column-switching (CS) high-performance liquid chromatography. Under the
      optimized conditions, only the sulphonamide drugs with an unsubstituted
      sulphonamide group were retained on the CA precolumn and separated on a reversed
      phase analytical column. Of these, the retention of hydrochlorothiazide (HCT),
      chlorothiazide, acetazolamide, furosemide (FS) and chlorthalidone was almost
      quantitative. The peak area of HCT was proportional to the concentration in the
      range of 1-100 nmol/mL with relative standard deviations of 3.7% (5 nmol/mL) and
      0.7% (100 nmol/mL). This CS system was applied to urine and plasma samples spiked
      with HCT and FS. Endogenous components of these were effectively removed, and HCT
      and FS were selectively retained on the CA precolumn. Almost quantitative
      recoveries and reproducibility were obtained.

PMID- 7812124
TI  - Measurement of theophylline metabolites produced by reaction with hepatic
      microsome by high performance liquid chromatography following solid phase
      extraction.
AB  - An analytical method has been developed with which to measure the microsomal
      enzyme activities responsible for oxidative theophylline metabolism. Three
      metabolites: 3-Methylxanthine (3-MX); 1-methylxanthine (1-MX); 1,3-dimethyluric
      acid (1,3-DMU), with acetaminophen as an internal standard (IS), were separated
      by solid phase extraction using a Sep-Pak C18 cartridge, followed by high
      performance liquid chromatography on a reversed-phase column with isocratic
      elution using 25 mM acetate buffer containing 4% acetonitrile and 2.5 mM tetra-n
      butylammonium hydrogen sulphate (pH 5.25) as the mobile phase. The analytes were
      clearly resolved and no interference with foreign peaks was observed. A linear
      relationship was obtained for the metabolites over the concentration range of 0.5
      5.0 micrograms/mL, and their analytical recovery was almost 100%. This method can
      be used to assess drug interactions involving alterations in the
      biotransformation of theophylline.

PMID- 7812125
TI  - TLC--a rapid method for liposome characterization.
AB  - One of the most important problems for the use of liposomes as a drug delivery
      system is the modification of the vesicle induced by the liquid medium in which
      they are introduced (blood plasma for in vivo studies and the saline buffer
      solution for in vitro studies). Using thin-layer chromatography (TLC) we compared
      the behaviour of phosphatidylcholine (used for liposomes preparation) to that of
      the following unfilled liposomes: multilamellar liposomes (MLV); small
      unilamellar vesicles (SUV); and reverse phase evaporation vesicles (REV), before
      and after storage for 15 min in Krebs-Henseleit solution (37 degrees C, pH 7.4,
      aerated continuously with 95% O2 + 5% CO2). All variants contained the same
      amount of phosphatidylcholine. Thin-layer chromatography was performed on silica
      gel 60 as adsorbent. Two types of solvents were tested: one based on
      chloroform/alcohol (n-butanol or n-propanol or methanol)/water mixture (in
      different ratios) and another based on alcohol/alcohol/water mixture (n-butanol/n
      propanol/water in 4/3/3 volume ratio). In all variants of chloroform containing
      solvents no differences were found between phosphatidylcholine and all types of
      liposomes. When using as solvent n-butanol/n-propanol/water significant
      differences were found between all types of liposomes before and after storage in
      Krebs-Henseleit solution. Their presence, after TLC treatment, was shown in
      electron microscopy studies.

PMID- 7812127
TI  - Separation of reducing monosaccharides by capillary zone electrophoresis.
AB  - The separation of reducing monosaccharides derived from glycosidoproteins and
      glycolipids by capillary zone electrophoresis (CZE) is dependent on the pH and
      concentration of the borate buffer. Five saccharides were completely separated in
      a fused silica capillary tube (50 microns i.d., 65 cm) containing 50 mM borate
      buffer (pH 10.5) as carrier, with high resolution, at an applied potential of 20
      kV after the reducing saccharides were derivatized with 1-naphthylamine. On
      column UV (254 nm) monitoring allowed quantitation of these saccharides at least
      in the concentration range of 10-100 mM in reaction solution. This method was
      applied to the determination of the monosaccharides composition of various
      carbohydrate materials to demonstrate its usefulness.

PMID- 7812126
TI  - Separation of vitamin B complex and folic acid using TLC plates impregnated with
      some transition metal ions.
AB  - The separation of Vitamin B complex and folic acid was achieved on silica gel
      layers impregnated with Mn++, Fe++, Co++, Ni++, Cu++, Cd++, Zn++, or Mg++ (0.1%,
      0.2%, 0.3%, 0.4% of each ion). Three new solvent systems n-propanol: n
      butanol:water:ammonia (7:5:1:2, by vol), n-propanol:n-butanol:water:ammonia
      (7:5:1:1.5, by vol), n-propanol:n-butanol:water:ammonia (7:5:0.75:2, by vol) were
      developed. The spots of vitamins were located by exposing the chromatoplate to
      iodine vapours.

PMID- 7812128
TI  - Improved resolution of tryptic digest fragments from haemoglobin variants using
      phytic acid in free zone capillary electrophoresis.
AB  - Capillary electrophoresis can be applied to the rapid characterization of tryptic
      digests of proteins. The addition of phytic acid to the separation buffer was
      found to improve resolution considerably when the technique was applied to
      differentiate between tryptic digests derived from variant haemoglobins.
      Moreover, analysis time was of the order of 15 min, which is considerably shorter
      than that obtained using gradient reversed-phase high-performance liquid
      chromatography or two-dimensional paper chromatography-electrophoresis.

PMID- 7812129
TI  - Family caregiving in the nineteenth century: Emily Hawley Gillespie and Sarah
      Gillespie, 1858-1888.

PMID- 7812130
TI  - Knots in the fabric: Richard Pearson Strong and the Bilibid Prison vaccine
      trials, 1905-1906.

PMID- 7812131
TI  - American medicine and the "organizational synthesis": Chicago physicians and the
      business of medicine, 1900-1920.

PMID- 7812132
TI  - Community and professionalization: general practitioners and ear, nose, and
      throat specialists in Cincinnati, 1945-1947.

PMID- 7812133
TI  - Freud studies, 1993-1994: a field establishes itself.

PMID- 7812134
TI  - Chemosensing and signal transduction in bacteria.
AB  - Major advances have been made over the past year in understanding the molecular
      mechanisms involved in membrane receptor function, and in resolving the global
      organization of intracellular signaling pathways. Crystallographic and
      biochemical studies are revealing details of transmembrane signaling mechanisms
      and the phosphorylation reactions of the two-component regulatory systems. In
      addition, the discovery of new signal transduction pathways and new inputs into
      known pathways are providing a clearer view of the basic architecture of the
      signal transduction networks within the bacterial cell.

PMID- 7812135
TI  - Termination of photoreceptor responses.
AB  - Vertebrate and invertebrate photoreceptors respond with great speed and
      sensitivity to the onset of light; however, they also adapt quickly to constant
      light or a reduction of illumination. During the past year or so, new information
      has become available concerning the molecular mechanisms by which photoreceptors
      recover from and adapt to stimuli. These data have identified mechanisms that
      inactivate nearly every step of the vertebrate and invertebrate phototransduction
      pathways. Light-induced changes in the concentration of intracellular Ca2+ play
      an important role in photoreceptor recovery and adaptation. Recently, several
      proteins that may mediate the effects of Ca2+ on phototransduction have been
      identified.

PMID- 7812136
TI  - Differences in transduction between rod and cone photoreceptors: an exploration
      of the role of calcium homeostasis.
AB  - Rod and cone photoreceptors respond to light with distinct sensitivity and
      kinetics. Recent biochemical and electrophysiological studies demonstrate that
      the enzymes of the phototransduction cascade are similar, but not identical, in
      these two photoreceptor types. In contrast, light or voltage stimulation
      generates changes in the cytoplasmic concentration of Ca2+ in the outer segment
      that are far larger and faster in cones than in rods. This distinction reflects
      rod-cone differences in each of the elements that control Ca2+ homeostasis: cell
      volume, the rate of Ca2+ clearance from the outer segment, the cytoplasmic Ca2+
      buffering, and the Ca2+ influx through cGMP-gated ion channels.

PMID- 7812137
TI  - Calcium signalling in hair cells: multiple roles in a compact cell.
AB  - Ca2+ is critical for mechanosensory adaptation, frequency tuning, afferent
      synaptic transmission, and efferent modulation in hair cells. These four
      processes involve cytoplasmic Ca2+ in three independent signalling pathways.
      Recent work suggests that Ca2+ regulates a myosin adaptation motor, and that a
      mobile Ca2+ buffer is highly concentrated in hair cells. Focal Ca2+ entry and the
      cytoplasmic Ca2+ buffer help to separate these pathways by limiting the spread of
      Ca2+ signals.

PMID- 7812138
TI  - Hair cell based amplification in the cochlea.
AB  - Recently, several reports have provided data about the way in which outer hair
      cells amplify sound within the cochlea. These include new measurements of hair
      cell forces in the cochlea and in isolated hair cells. In addition, theoretical
      advances that synthesize such experiments and show how hair cells might tune up
      the cochlear response sound promising.

PMID- 7812139
TI  - Regeneration of hair cells in the vestibulocochlear system of birds and mammals.
AB  - Regeneration of hair cells leads to a structural and functional recovery in the
      mature avian vestibular and auditory sensory epithelia. This regeneration
      replaces hair cells that have been lost as a result of noise damage, ototoxic
      drug poisoning, or other trauma. Recent findings suggest that it may be possible
      to induce a similar mechanism for repair in the vestibular and auditory epithelia
      of mammals, including humans.

PMID- 7812140
TI  - Survival factors in retinal degenerations.
AB  - Recent experiments on the retina have examined the effectiveness of various
      factors (e.g. growth factors, neurotrophins and cytokines) for enhancing survival
      and reducing injury of retinal neurons, such as photoreceptors and ganglion
      cells, whose death leads to blindness in degenerative retinal diseases. It has
      also been shown that retinal injury stimulates intrinsic survival mechanisms that
      promote survival of these neurons.

PMID- 7812141
TI  - The pathophysiology of chronic pain--increased sensitivity to low threshold A
      beta-fibre inputs.
AB  - Chronic pain is characterized by abnormal sensitivity, which is due to the
      generation of pain in response to the activation of the low-threshold
      mechanoreceptive A beta fibres that normally generate innocuous sensations. Three
      different processes in the spinal cord can account for this dramatic alteration
      in sensory processing in the somatosensory system: increased excitability,
      decreased inhibition and structural reorganization. All have been shown to occur
      and each may contribute separately or together to the wide range of chronic
      inflammatory and neuropathic pain disorders. The unravelling of the cellular
      mechanisms involved both offers the potential for developing novel therapeutic
      strategies, which reduce functional synaptic plasticity and prevent central
      atrophic and regenerative responses in injured neurones, and illustrates the
      capacity of the adult nervous system for maladaptive modification.

PMID- 7812142
TI  - Development, critical period plasticity, and adult reorganizations of mammalian
      somatosensory systems.
AB  - This review covers recent progress in three major areas of investigation in
      somatosensory systems: development, developmental plasticity and functional
      reorganization. Important findings relate to the development of periphery-related
      patterning in thalamic afferents to somatosensory cortex, the controversial role
      of neural activity in the development and plasticity of periphery-related
      afferent patterning in the brainstem and cortex, experience-dependent
      reorganizations in adult somatosensory cortex, and the locus of these changes.

PMID- 7812143
TI  - Cortical circuitry in a dish.
AB  - In the mammalian neocortex, local connections as well as projections to and from
      the cortex are organized in cortical layers. Recent studies have demonstrated
      that the formation of the patterns of afferent and efferent cortical connections
      in organotypic co-cultures are similar to those observed in vivo. These findings
      provide some insights into the cellular strategies that operate during the
      development of layer-specific cortical connections.

PMID- 7812145
TI  - Neural substrates of sound localization.
AB  - Recent behavioral experiments suggest that parallel pathways in the forebrain and
      midbrain are capable of mediating sound localization. Neurophysiological studies
      have advanced our understanding of how binaural and monaural localization cues
      contribute to the representations of auditory space within these pathways.
      Experience-dependent modifications of auditory spatial tuning in both the
      forebrain and midbrain pathways indicate that sensory input during development
      customizes an individual's neural processing of spatial information.

PMID- 7812144
TI  - Sensory gating mechanisms of the thalamus.
AB  - The thalamus is an obligatory station through which nearly all sensory
      information must pass before reaching the cerebral cortex. One of the major
      functions of the thalamus is the selective control of the flow of sensory-motor
      information to the cerebral cortex during different states of the sleep-wake
      cycle and arousal, and is controlled through the actions of various
      neurotransmitter systems in the brainstem, hypothalamus, and cerebral cortex.
      Recent investigations have detailed the cellular mechanisms, including the role
      of GABAA and GABAB receptors, involved in the generation of both normal (e.g.
      spindle waves) and abnormal (e.g. generalized seizures) patterns of activity in
      thalamocortical circuits. In addition, in vivo investigations have also revealed
      that the dense projection from the cerebral cortex to the thalamus may
      synchronize thalamocortical activity in a manner useful for sensory analysis.
      Together, these data suggest that oscillations and synchronization are important
      for both normal and abnormal function in thalamocortical circuits.

PMID- 7812146
TI  - Linearity of synaptic interactions in the assembly of receptive fields in cat
      visual cortex.
AB  - Recent extra- and intracellular recordings from simple cells in the striate
      cortex have led to the development of detailed models of how novel receptive
      field properties are generated by the neuronal circuitry of the cortex. The first
      stage in assembling simple receptive fields appears to be a linear combination of
      visual inputs. The output of the linear stage is then normalized by a contrast
      gain control mechanism. Finally, a threshold and expansive nonlinearity in the
      spike-generating mechanism enhances selectivity for stimulus features such as
      orientation, direction, and spatial frequency.

PMID- 7812147
TI  - Noise, neural codes and cortical organization.
AB  - Cortical circuitry must facilitate information transfer in accordance with a
      neural code. In this article we examine two candidate neural codes: information
      is represented in the spike rate of neurons, or information is represented in the
      precise timing of individual spikes. These codes can be distinguished by
      examining the physiological basis of the highly irregular interspike intervals
      typically observed in cerebral cortex. Recent advances in our understanding of
      cortical microcircuitry suggest that the timing of neuronal spikes conveys
      little, if any, information. The cortex is likely to propagate a noisy rate code
      through redundant, patchy interconnections.

PMID- 7812148
TI  - Plasticity in auditory cortical circuitry.
AB  - Recent studies have focused on the mechanisms and conditions yielding the short-
      and long-term plasticity exhibited by neuronal responses in the primary auditory
      cortex of adults. These investigations have examined factors operating at the
      cellular and intercellular levels, the effects of global behavioral states and
      the role of the cholinergic system, which could mediate between the global and
      local levels. A behaviorally gated unsupervised Hebbian-covariance rule can
      explain most of the bottom-up driven changes that were observed following sensory
      manipulation. However, additional supervised learning mechanisms are probably
      required to generate behavioral improvement. This suggestion has not yet been
      tested directly.

PMID- 7812149
TI  - A molecular dissection of spatial patterning in the olfactory system.
AB  - The identification and cloning of genes encoding odorant receptors has provided
      molecular probes with which to examine the molecular mechanisms and
      organizational strategies underlying olfactory information processing. Recent
      studies using odorant receptor genes have revealed unexpected patterns of
      expression that provide new insights into how information may be organized in the
      nose and in the axonal projection from the nose to the brain.

PMID- 7812150
TI  - Sensory systems.

PMID- 7812152
TI  - 113Cd-1H heteroTOCSY: a method for determining metal-protein connectivities.
AB  - 113Cd-1H NMR correlation experiments have been extremely useful for determining
      the amino acid ligands that form metal-binding sites in proteins. To date, the
      majority of these methods have used heteronuclear multiple-quantum transfer as
      the basis for establishing correlations. In this paper, we demonstrate the
      feasibility of using correlation methods that employ heteronuclear cross
      polarization (heteroTOCSY) as viable alternatives. Additionally, we couple
      heteroTOCSY with selective excitation and transfer procedures to take advantage
      of the small number of heteronuclei usually present in metalloprotein systems.
      One- and two-dimensional experiments are presented as examples of these
      techniques.

PMID- 7812151
TI  - 1H and 15N resonance assignments and secondary structure of cellular retinoic
      acid-binding protein with and without bound ligand.
AB  - Sequence-specific assignments for the 1H and 15N backbone resonances of cellular
      retinoic acid-binding protein (CRABP), with and without the bound ligand, have
      been obtained. Most of the side-chain resonances of both apo- and holo-CRABP have
      also been assigned. The assignments have been obtained using two-dimensional
      homonuclear and heteronuclear NMR data, and three-dimensional 1H-15N TOCSY-HMQC
      and NOESY-HMQC experiments. The secondary structure, deduced from nuclear
      Overhauser effects, amide H/D exchange rates and H alpha chemical shifts, is
      analogous in both forms of the protein and is completely consistent with a model
      of CRABP that had been constructed by homology with the crystal structure of
      myelin P2 protein [Zhang et al. (1992) Protein Struct. Funct. Genet., 13, 87-99].
      This model comprises two five-stranded beta-sheets that form a sandwich or beta
      clam structure, and a short N-terminal helix-turn-helix motif that closes the
      binding cavity between the two sheets. Comparison of the data obtained for apo-
      and holo-CRABP indicates that a region around the C-terminus of the second helix
      is much more flexible in the apo-protein. Our data provide experimental evidence
      for the hypothesis that the ligand-binding mechanism of CRABP, and of other
      homologous proteins that bind hydrophobic ligands in the cytoplasm, involves
      opening of a portal to allow entry of the ligand into the cavity.

PMID- 7812153
TI  - Resonance assignment of methionine methyl groups and chi 3 angular information
      from long-range proton-carbon and carbon-carbon J correlation in a calmodulin
      peptide complex.
AB  - Several simple 3D experiments are used to provide J correlations between
      methionine C epsilon methyl carbons and either the C gamma H2 protons or C beta
      and C gamma. The intensity of the J correlations provides information on the size
      of the three-bond J couplings and thereby on the chi 3 torsion angle. In
      addition, a simple 3D version of the HMBC experiment provides a sensitive link
      between the C epsilon H3 methyl protons and C gamma. The methods are demonstrated
      for a 20 kDa complex between calmodulin and a 26-residue peptide fragment of
      skeletal muscle myosin light chain kinase.

PMID- 7812154
TI  - An evaluation of least-squares fits to COSY spectra as a means of estimating
      proton-proton coupling constants. I. Simulated test problems.
AB  - A computational method is described that takes an initial estimate of the
      chemical shifts, line widths and scalar coupling constants for the protons in a
      molecule, and refines this estimate so as to improve the least-squares fit
      between an experimental COSY spectrum and the spectrum simulated from these
      parameters in the weak-coupling approximation. In order to evaluate the potential
      of such refinements for estimating these parameters from COSY experiments, the
      method has been applied to a large number of sample problems which were
      themselves simulated from standard conformations of the amino acids, along with
      25 near-native conformations of the protein bovine pancreatic trypsin inhibitor.
      The results of this evaluation show that: (i) if the chemical shifts are known to
      within ca. 0.01 ppm and no noise or artifacts are present in the data, the method
      is capable of recovering the correct coupling constants, starting from
      essentially arbitrary values, to within 0.1 Hz in almost all cases. (ii) Although
      the precision of these estimates of the coupling constants is degraded by the
      limited resolution, noise and artifacts present in most experimental spectra, the
      large majority of coupling constants can still be recovered to within 1.0 Hz; the
      local minimum problem is not made significantly worse by such defects in the
      data. (iii) The method assigns an 'effective' line width to all the resonances,
      and in the process can resolve overlapping cross peaks. (iv) The method is not
      capable of determining the chemical shifts a priori, due to the presence of
      numerous local minima in the least-squares residual as a function of these
      parameters.

PMID- 7812155
TI  - An evaluation of least-squares fits to COSY spectra as a means of estimating
      proton-proton coupling constants. II. Applications to polypeptides.
AB  - A new computational method for simultaneously estimating all the proton-proton
      coupling constants in a molecule from COSY spectra [Yang, J.-X. and Havel, T.F.
      (1994) J. Biomol. NMR, 4, 807-826] is applied to experimental data from two
      polypeptides. The first of these is a cyclic hexapeptide denoted as VDA (-D-Ala1
      Phe2-Trp3-Lys(Z)4-Val5-Phe6-), in deuterated DMSO, while the second is a 39
      residue protein, called decorsin, in aqueous solution. The effect of different
      data processing strategies and different initial parameter values on the accuracy
      of the coupling constants was explored. In the case of VDA, most of the coupling
      constants did not depend strongly on the initial values chosen for the
      optimization or on how the data were processed. This, together with our previous
      experience using simulated data, implies strongly that these values are accurate
      estimates of the coupling constants. They also differ by an average of only 0.36
      Hz from the values of the 14 coupling constants that could be measured
      independently by established methods. In the case of decorsin, many of the
      coupling constants exhibited a moderate dependence on their initial values and a
      strong dependence on how the data were processed. With the most successful data
      processing strategy, the amide-alpha coupling constants differed by an average of
      1.11 Hz from the 21 values that could be measured by established methods, while
      two thirds of the three-bond coupling constants fell within 1.0 Hz of the ranges
      obtained by applying the Karplus relation to an independently computed ensemble
      of distance geometry structures. The averages of the coupling constants over
      multiple optimizations using random initial values were computed in order to
      obtain the best possible estimates of the coupling constants. Most clearly
      incorrect averages can be identified by large standard deviations in the coupling
      constants or the associated line widths and chemical shifts, and can be explained
      by strong coupling and/or overlap with the water signal, the diagonal peaks or
      other cross peaks.

PMID- 7812156
TI  - Backbone 1H and 15N resonance assignments of the N-terminal SH3 domain of drk in
      folded and unfolded states using enhanced-sensitivity pulsed field gradient NMR
      techniques.
AB  - The backbone 1H and 15N resonances of the N-terminal SH3 domain of the Drosophila
      signaling adapter protein, drk, have been assigned. This domain is in slow
      exchange on the NMR timescale between folded and predominantly unfolded states.
      Data were collected on both states simultaneously, on samples of the SH3 in near
      physiological buffer exhibiting an approximately 1:1 ratio of the two states. NMR
      methods which exploit the chemical shift dispersion of the 15N resonances of
      unfolded states and pulsed field gradient water suppression approaches for
      avoiding saturation and dephasing of amide protons which rapidly exchange with
      solvent were utilized for the assignment.

PMID- 7812157
TI  - Differential deuterium isotope shifts and one-bond 1H-13C scalar couplings in the
      conformational analysis of protein glycine residues.
AB  - The one-bond deuterium isotope shift effect for glycine C alpha resonances
      exhibits a conformational dependence comparable to that of the corresponding 1JHC
      scalar coupling in both magnitude (approximately 11 Hz at 14.1 T) and dihedral
      angle dependence. The similarity in the conformational dependence of the 1JHC and
      deuterium isotope shift values suggests a common physical basis. Given the known
      distribution of (phi, psi) main-chain dihedral angles for glycine residues, the
      deuterium isotope shifts and the 1JHC scalar couplings can determine
      conformations in the left- and right-handed helical-to-bridge regions of the
      (phi, psi) plane to an accuracy of approximately 13 degrees. In the absence of
      stereochemical assignments, the differential deuterium isotope shifts and the
      1JHC scalar couplings can be combined with limited independent structural
      information (e.g., the sign of phi) to determine the chirality of the deuterium
      substitution.

PMID- 7812158
TI  - Measurement of HN-H alpha J couplings in calcium-free calmodulin using new 2D and
      3D water-flip-back methods.
AB  - Two new methods are described for the measurement of three-bond JHNH alpha
      couplings in proteins isotopically enriched with 15N. Both methods leave the
      water magnetization in an unsaturated state, parallel to the z-axis, and
      therefore offer significant enhancements in sensitivity for rapidly exchanging
      backbone amide protons. The J couplings can be measured either from a set of
      constant-time 2D 1H-15N HMQC spectra, which are modulated in intensity by JHNH
      alpha, or from a water-flip-back version of the 3D HNHA experiment. The method is
      demonstrated for a sample of calcium-free calmodulin. Residues Lys75-Asp80 have
      JHNH alpha values in the 6-7 Hz range, suggesting that a break in the 'central
      helix' occurs at the same position as previously observed in solution NMR studies
      of Ca(2+)-ligated calmodulin.

PMID- 7812159
TI  - 5th meeting of the European Society for Pigment Cell Research. Vienna, Austria,
      19-22 October 1994. Program and abstracts.

PMID- 7812160
TI  - MHC-linked colonization of the thymus and thymocyte development: effects of
      mature T lymphocytes.
AB  - Effects of mature T lymphocytes on thymic colonization by lymphohemopoietic cells
      were investigated in an in vitro experimental model, using a variety of
      experimental strategies. Lymphoid-depleted fetal thymus (FT) explants (C57BL/Ka,
      Thy1.1, H-2b) were incubated with bone marrow (BM) cells from syngeneic
      (C57BL/Ka; SBM) and allogeneic (BALB/c, Thy1.2, H-2d; ABM) donors. Cocultures of
      FT with SBM and ABM, depleted of Thy1+ or of CD3+ cells, resulted in equal
      proportions of lymphocytes from both BM donors. When peripheral blood lymphocytes
      (PBL) from synegenic or semi-allogeneic donors (F1[C57BL/Ka x C57BL/6J],
      Thy1.1/Thy1.2); or F1[C57BL/Ka x BALB/c], Thy1.1/Thy1.2, respectively) were added
      to these cultures, the total lymphocyte count per thymic lobe decreased and a
      developmental preference of the SBM-derived cells, as compared to the ABM-derived
      cells, was noted. Cells of the PBL types were also observed in the cultures.
      Cocultures of FT with ABM and PBL showed reduced proportions of ABM-derived cells
      and occurrence of cells of the PBL type. Finally, FT explants partially depleted
      of lymphocytes by irradiation (6 Gy), were cocultured with PBL from either
      syngeneic or allogeneic donors. In the presence of syngeneic PBL, the total
      number of cells and the proportion of double-positive (CD4+CD8+) T cells were
      similar to those in the FT cultured by itself, whereas in the presence of
      allogeneic PBL these values were reduced. The study suggests that mature T
      lymphocytes may play a role in the developmental processes in the thymus, and
      points to MHC-linked selective effects.

PMID- 7812161
TI  - Endogenous corticosteroids modulate lymphoproliferation and susceptibility to
      experimental allergic encephalomyelitis in the Brown Norway rat.
AB  - Successful induction of the experimental autoimmune disease allergic
      encephalomyelitis (EAE) depends, in part, upon species susceptibility. The Lewis
      rat is highly susceptible to EAE whereas the Brown Norway (BN) strain is
      resistant to induction. Endogenous glucocorticoids influence the manifestation of
      the disease and recovery from neurological deficits. Moreover, abrogation of the
      curative steroid-mediated effects converts the condition to a terminal state. In
      the present study treatment of EAE-inoculated BN rats with the steroid antagonist
      RU486 (Mifepristone) failed to influence the resistance to symptoms. Similarly,
      adrenalectomy (ADX) prior to sensitisation did not allow the development of
      clinical EAE but did facilitate neuroperivascular accumulation of inflammatory
      type cells. However, RU486 treatment after ADX induced neurological and
      histological signs of EAE in the majority of animals. Lymphocyte proliferation
      studies on cells isolated from BN rats treated with RU486 revealed an enhanced
      responsiveness to mitogenic and antigenic stimulation. These results strongly
      implicate endogenous steroids in the expansion of immune cell numbers which would
      be an absolute requirement for the expression of autoimmune-based neurological
      disease in otherwise resistant rats.

PMID- 7812162
TI  - Multiple isoforms of the human pentraxin serum amyloid P component.
AB  - Human serum amyloid P component (SAP) isolated from 20 healthy individuals was
      analyzed by anion exchange chromatography and isoelectric focusing (IEF) in order
      to investigate the existence of multiple forms of SAP and interindividual
      structural differences. Anion exchange chromatography showed one major and
      several minor subpopulations of SAP. IEF of all SAP isolates showed a previously
      unreported degree of heterogeneity with six isoelectric forms (pKi range 5.5-6.1)
      and with minor interindividual differences in respect of isoelectric points.
      Total enzymatic deglycosylation of SAP reduced the number of bands in IEF to two
      indicating the existence of two types of polypeptide chains.

PMID- 7812163
TI  - Superantigens: the paradox of T-cell activation versus inactivation.
AB  - Superantigens are interesting for several reasons. They exhibit unusual T-cell
      activation characteristics, they allow to follow in vivo ligand-reactive T cells,
      they cause T-cell-mediated shock symptoms and they may be causally involved in
      certain human diseases. This review focuses on the paradox of T-cell activation
      versus T-cell inactivation as caused by bacterial superantigens in vivo. T-cell
      activation leads to the acute release of toxic concentrations of lymphokines
      including tumor necrosis factor alpha/beta, gamma-interferon, interleukin (IL)-2,
      IL-4 and IL-10. T-cell inactivation mirrors induction of anergy, T-cell receptor
      downregulation, and that of CD2, CD4 and CD8 cell surface molecules, as well as
      of apoptosis. Two waves of apoptosis cripple the T-cell repertoire of
      superantigen-reactive T cells, an immediate one being induced within 24 h and a
      late one occurring at days 3-4. In between, clonal expansion of anergic ligand
      reactive T cells takes place.

PMID- 7812164
TI  - Human hybridomas secreting monoclonal antitreponemal antibodies raised after in
      vitro stimulation of human lymphocytes.
AB  - Peripheral blood lymphocytes from patients with syphilis were stimulated in vitro
      against Treponema pallidum extract and consequently were fused with mouse myeloma
      cells to raise heterohybridomas secreting specific human antibodies. In these
      experiments, 5 heterohybridomas were selected which were shown to secrete
      monoclonal antibodies which recognized treponemal antigens. Some of the
      monoclonal (Mab 1C12, Mab 1D11) react with antigens specific to T. pallidum while
      others (Mab 2A2, Mab 2C8, Mab 2C11) bind to treponemal components which
      demonstrated group specificity.

PMID- 7812165
TI  - Delayed hypersensitivity and HLA in smear-positive pulmonary tuberculosis.
AB  - Tuberculin responses were quantified by induration of the skin, velocity of blood
      flow in dermal microcirculation and composition of the cellular infiltrate in 125
      patients with tuberculosis and 39 healty controls. The diameters of the
      tuberculin responses were greater in HLA-DR15-positive patients than in DR15
      negative patients. The density of infiltrating CD(4+)-positive cells showed a
      positive correlation with induration in DR15-negative subjects (r = 0.54). A
      fraction of DR15-positive patients gave large tuberculin responses (> or = 15 mm)
      but with few CD4+ cells in the test site (< 500/mm2); these patients had a
      greater percentage of cells in the diffuse dermal infiltrate than in the
      perivascular region, greater blood flow velocities in the tuberculin response but
      more frequently with central relative slowing of blood flow and had higher total
      IgG and specific antimycobacterial antibody levels compared to other DR15
      positive patients. If the inflammatory infiltrate in the lungs parallels that in
      the tuberculin skin test, the lack of immunocompetent cells and tissue hypoxia
      could permit pulmonary cavitation and explain the association of HLA-DR15 with
      smear-positive pulmonary tuberculosis.

PMID- 7812166
TI  - Inhibition of allergen-induced IgE and IgG1 production by soluble IL-4 receptor.
AB  - In this study, the effect of soluble IL-4 receptors (sIL-4R) on murine allergen
      induced IgE and IgG1 production was examined. Lymphocytes from mice sensitized to
      the allergens ragweed (RW) or ovalbumin (OVA) in vivo were restimulated in vitro
      with the sensitizing allergen in the presence of either a soluble murine sIL-4R,
      a dimeric sIL-4R Ig fusion protein (sIL-4R/Fc), or anti-IL-4 antibody in 14-day
      cultures. Both monomeric and dimeric sIL-4R inhibited polyclonal IgE
      (approximately 70%) and IgG1 (approximately 35%) production in a dose-dependent
      fashion, similar to that observed in the presence of the anti-IL-4 antibody.
      Allergen-specific IgE and IgG1 were inhibited to a greater degree. Addition of
      sIL-4R was most effective when present in the culture during the first 3 days and
      added not later than day 6. In kinetic experiments, we distinguished ongoing IgE
      production from precommitted B cells versus newly induced IgE synthesis and found
      that newly induced IgE production was the major target of the sIL-4Rs. These data
      demonstrate the efficacy of sIL-4R in inhibiting the early stages of the IgE B
      cell maturation pathway and indicate the potential of sIL-4R for the inhibition
      of IgE production in vivo.

PMID- 7812167
TI  - Biomolecular regulation of the IgE immune response. II. In vitro IgE synthesis
      and spontaneous production of cytokines.
AB  - Distinct subtypes of T-helper cells have been incriminated as sources of a common
      regulatory mechanism behind IgE synthesis and eosinophil activation in IgE
      mediated diseases. To investigate whether IgE-producing cells are in fact
      stimulated in vivo or have an increased susceptibility to certain stimuli, the in
      vitro IgE synthesis was compared for different patient groups. Peripheral blood
      mononuclear cells (PBMC) were isolated from three groups of donors: (1) patients
      with atopic dermatitis and high levels of serum IgE (> 5000 IU/ml, n = 11); (2)
      patients with diagnosed inhalant allergy and serum IgE in the range of 200-2,000
      IU/ml (n = 10), and (3) nonallergic donors with serum IgE below 100 IU/ml (n =
      10). PBMC were tested for the spontaneous and IL-4-induced IgE synthesis in 11
      day cultures during which adhering cells were removed on day 2 by transferring
      the suspended cells and the medium to new wells. The three groups differed
      markedly in their capacity to synthesize IgE. The atopic dermatitis group
      demonstrated high spontaneous IgE synthesis (median 11.8 ng/ml), which was
      doubled (24.3 ng/ml, p < 0.05) by stimulation by IL-4. The two other groups had
      low spontaneous synthesis (0.7 and 0.3 ng/ml) but this increased (1.7 and 0.7
      ng/ml, p < 0.01) upon IL-4 stimulation. The spontaneous production of IFN-gamma
      in the cultures did not differ between the groups, but upon stimulation with
      phorbol myristate acetate, the atopic dermatitis group demonstrated significantly
      lower IFN-gamma levels compared to the two other groups. The IL-4 production in
      the cultures were generally below the detection limit (100 pg/ml), and whereas
      plasma levels of 1-2 ng/ml of soluble IL-4 receptor could be detected in all
      donors, no differences could be detected between the groups. These data suggest
      that reduced ability in atopic dermatitis of mounting an IFN-gamma response may
      account for the high levels of plasma IgE and IgE synthesis found in these
      patients.

PMID- 7812168
TI  - Genetic analysis of IgE and the IGHE, IGHEP1 and IGHEP2 genes in atopic families.
AB  - The familial occurrence of allergic diseases was studied in 478 individuals and
      their family members. The results showed that there was pronounced familial
      clustering. Total serum IgE concentrations of atopic patients and their parents
      were well correlated. Moreover, the concentration of specific IgE of the patients
      and their parents was also well correlated, suggesting that IgE production was
      genetically determined. To determine if major structural abnormalities of IGHE,
      IGHEP1 and IGHEP2 genes might lead to aberrant control and subsequent increase in
      IgE concentration, genomic DNAs from 55 individuals, i.e., 31 atopic patients and
      their family members, were examined. We detected the IGHE, IGHEP1 and IGHEP2
      genes in all 55 leukocyte DNAs. We could not find any large deletions or
      duplications in the IGHE, IGHEP1 and IGHEP2 genes of atopic patients with high
      serum IgE concentrations.

PMID- 7812169
TI  - Effect of ZCR-2060, an antiallergic agent, on antigen-induced immediate- and late
      phase increases in airway resistance in sensitized guinea pigs.
AB  - The effect of 2-[2-[4-(diphenylmethyl)-1-piperadinyl]ethoxy] benzoic acid maleate
      (ZCR-2060) on passive systemic anaphylaxis (PSA) and antigen-induced immediate-
      and late-phase increase in airway resistance (Rrs) in either passively or
      actively sensitized guinea pigs were investigated. ZCR-2060 inhibited PSA in
      guinea pigs. ID50 values of ZCR-2060, ketotifen, terfenadine and cetirizine on
      PSA were 0.03, 0.02, 0.8 and 0.3 mg/kg, respectively, when administered orally 1
      h before the antigen challenge. The protective effect of ZCR-2060 was observed
      until 12 h before the antigen challenge. Aeroantigen-induce immediate increase in
      Rrs in passively sensitized guinea pigs with and without metyrapone treatment was
      inhibited by ZCR-2060, ketotifen, terfenadine and cetirizine. In contrast,
      prednisolone did not affect the aeroantigen-induced immediate increase in Rrs in
      animals not treated with metyrapone, but significantly inhibited the metyrapone
      induced enhanced immediate response. In actively sensitized animals, the
      immediate- and late-phase increases in Rrs were observed within 30 min and
      between 3 and 8 h after the aeroantigen challenge. Pretreatment with metyrapone
      accelerated both antigen-induced responses. ZCR-2060 (1 mg/kg) significantly
      inhibited both responses. Ketotifen (1 mg/kg), terfenadine (10 mg/kg) and
      prednisolone (10 mg/kg) significantly the inhibited the late-phase response, but
      did not affect the immediate-phase response. In contrast, Cetirizine (10 mg/kg)
      did not affect either response. The effect of ZCR-2060 on late-phase response was
      stronger than that of ketotifen, terfenadine and cetirizine, and was almost the
      same as that of prednisolone. These results suggest that ZCR-2060 has a potent
      protective effect on immediate- and late-phase increases in Rrs.

PMID- 7812170
TI  - Mechanisms of action of antiphospholipid antibodies in the antiphospholipid
      syndrome.
AB  - Antiphospholipid antibody syndrome (APS) is characterized by autoantibodies
      against negatively charged phospholipids in the serum, and clinically by multiple
      thromboses, thrombocytopenia, and recurrent fetal loss. The mechanism(s) by which
      the antibodies cause the clinical picture are not clear. We review the possible
      mechanisms of action of antiphospholipid (aPL) antibodies. Apparently, aPL
      antibodies act by interfering with coagulation, involving both endothelial cells,
      platelets, and humoral components, and affect pregnancy outcome by interfering
      with embryo implantation and fetal development.

PMID- 7812171
TI  - Strain-related differences in the tracheal responsiveness of sensitized guinea
      pig.
AB  - The purpose of this study was to evaluate the strain-related differences in
      tracheal hyperresponsiveness in control and egg albumen-sensitized guinea pigs.
      Concentration-response curves to acetylcholine and barium chloride were
      established from tracheal rings of Dunkin-Hartley and BFA strain guinea pigs. In
      the Dunkin-Hartley strain, sensitization did not significantly increase the
      tracheal responsiveness to acetylcholine and barium chloride. By contrast, in the
      BFA strain, significant sensitization-induced hyperreactivity was achieved as the
      maximal contractions induced by acetylcholine and barium chloride, were enhanced
      from 6.5 +/- 1.2 and 3.2 +/- 0.4 mN in control to 10.0 +/- 1.4 and 5.6 +/- 0.8
      mN, respectively, in sensitized animals. However, antigen challenge, performed in
      vitro, exhibited a similar amplitude of contraction in tracheal rings from both
      strains (Dunkin-Hartley 5.1 +/- 0.8 mN; BFA 5.9 +/- 0.5 mN). Finally, while the
      two guinea-pig strains developed specific sensitization to allergen, only
      tracheal rings from the BFA strain developed hyperresponsiveness to acetylcholine
      and barium chloride. The strain-related difference appears to be partly explained
      by a lower basal reactivity in the BFA strain both acetylcholine (Em 7.3 +/- 1.7
      and 6.5 +/- 1.2 mN for Dunkin-Hartley and BFA, respectively) and barium chloride
      (Em 9.4 +/- 2.6 and 3.2 +/- 0.4 mN for Dunkin-Hartley and BFA, respectively). As
      the same procedure of sensitization provides different results in the genesis of
      hyperreactivity between the two guinea-pig strains used for asthma models, the
      BFA guinea-pig strain seems to be a better model because sensitized non
      challenged animals could easily be dissociated from control ones, similar to that
      which occurs in asthmatic patients during provocation tests with cholinergic
      drugs.

PMID- 7812172
TI  - Autoimmune vasculitis preceding aspirin-induced asthma.
AB  - Two female patients have been described in whom peripheral vasculitis with cold
      sensitivity preceded by about 5 years typical symptoms of aspirin-induced asthma.
      Vasculitis was immunologically mediated and took the form of either limited
      cutaneous scleroderma or perniosis. Antinuclear autoantibodies of SS-B
      specificity were present in the serum. Challenge with aspirin provoked asthma and
      distinct blood circulation disturbance in the hands. It is speculated that in
      these patients vasculitis and asthma were causally linked, and leukotrienes
      mediated bronchial and vascular reactions that occurred simultaneously following
      aspirin administration.

PMID- 7812173
TI  - Face recognition as a function of social attention in non-human primates: an ERP
      study.
AB  - Epidural event related potentials (ERPs) were recorded from four squirrel monkeys
      (Saimiri sciureus) during the presentation of pictoral stimuli that comprised
      real human and monkey faces. Subjects viewed tachistoscopically presented stimuli
      belonging to four different categories: familiar and unfamiliar human faces, and
      familiar and unfamiliar monkey faces. Familiar faces were subcategorized into
      top, middle and bottom according to the perceived individual's dominance ranking
      in a social hierarchy, as rated by human judges observing the group's social
      behavior. Waveform peak components to monkey and human faces showed similarities
      in their spatial distribution. However, larger amplitude N1 and N2 components
      were elicited in response to monkey compared to human faces, particularly over
      lateral temporo-parietal sites. A similar trend was observed for the P3
      component, with maximal differences along midline electrode site. Responses to
      familiar and unfamiliar monkey faces showed larger N1s to familiar monkey faces
      and larger P3s to unfamiliar monkey faces. N1 and P3 components elicited by human
      faces showed no significant differences between conditions. N2 amplitudes were
      larger over posterior sites for top-ranked monkeys and larger over frontal sites
      for middle- and bottom-ranked monkeys. Top-ranked human faces elicited the
      largest N2 components, middle-ranked faces the next largest, and bottom-ranked
      faces the smallest. N1, N2, and P3 latencies were similarly sensitive to the
      ranking of human but not monkey faces. These data suggest that non-human primates
      exhibit evoked potentials to conspecific and non-conspecific faces that are
      similar in morphology but different in function. Larger amplitude responses to
      monkey faces suggests increased processing for that category of stimuli.
      Additionally, monkey ERPs reflect familiarity with conspecifics but not with
      human faces. Finally, the social status of the perceived individual, or at least
      the perceived threat posed by an individual, affects the latencies and magnitudes
      of ERP components produced by the viewer. These data are consistent with social
      attention hypotheses which propose that higher status (i.e. more dominant or
      socially meaningful) members of a group receive more attention than lower status
      individuals.

PMID- 7812174
TI  - Auditory M100 component 1: relationship to Heschl's gyri.
AB  - This study was designed to localize the neuroanatomic generator of the 100 ms
      latency magnetic auditory evoked field (EF) component (M100) activated by an
      unattended tone pip. Magnetic EFs in response to 25 ms duration, 90 dB, 1 kHz
      tone pips were recorded from both hemispheres of nine normal adults, five males
      and four females, using a seven-channel second-order gradiometer. The source of
      the M100 was estimated, with confidence intervals, by a least squares based
      inverse solution algorithm. Magnetic resonance (MR) images of the brain were
      acquired with a 1.5 T system using a standard head coil. The superior temporal
      gyri (STG) were manually segmented from 1.7 mm thick coronal images, and the
      superior surfaces were then rendered from the 3-D volume data. Translation and
      rotation matrices were identified to locate the magnetoencephalography (MEG)
      determined sources within the reconstructed STGs. This population of 18 STGs in 9
      individuals demonstrated two transverse gyri in 4 of 9 left hemispheres, and 5 of
      9 right hemispheres. All 9 left hemisphere M100 sources were in or included
      Heschl's gyrus(i) in the confidence intervals. Seven of the 9 included Heschl's
      gyrus(i) on the right: the remaining two, both males, had sources slightly
      anterior to Heschl's gyrus(i). We conclude that all M100 source location
      estimates were compatible with an auditory koniocortex source in or adjacent to
      Heschl's gyri.

PMID- 7812175
TI  - Brain potentials during mental arithmetic: effects of extensive practice and
      problem difficulty.
AB  - Recent behavioral investigations indicate that the processes underlying mental
      arithmetic change systematically with practice from deliberate, conscious
      calculation to automatic, direct retrieval of answers from memory [Bourne,
      L.E.Jr. and Rickard, T.C., Mental calculation: The development of a cognitive
      skill, Paper presented at the Interamerican Congress of Psychology, San Jose,
      Costa Rica, 1991: Psychol. Rev., 95 (1988) 492-527]. Results reviewed by
      Moscovitch and Winocur [In: The handbook of aging and cognition, Erlbaum,
      Hillsdale, NJ, 1992, pp. 315-372] suggest that consciously controlled processes
      are more dependent on frontal lobe function than are automatic processes. It is
      appropriate, therefore to determine whether transitions in the locus of primary
      brain activity occur with practice on mental calculation. In this experiment, we
      examine the relationship between characteristics of event-related brain
      potentials (ERPs) and mental arithmetic. Single-digit mental multiplication
      problems varying in difficulty (problem size) were used, and subjects were
      trained on these problems for four sessions. Problem-size and practice effects
      were reliably found in behavioral measures (RT). The ERP was characterized by a
      pronounced late positivity after task presentation followed by a slow wave, and a
      negativity during response indication. These components responded differentially
      to the practice and problem-size manipulations. Practice mainly affected
      topography of the amplitude of positivity and offset latency of slow wave, and
      problem-size mainly offset latency of slow wave and pre-response negativity.
      Fronto-central positivity diminished from session to session, and the focus of
      positivity centered finally at centro-parietal regions.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7812176
TI  - Effects of stimulus rate on signal response during functional magnetic resonance
      imaging of auditory cortex.
AB  - Functional magnetic resonance imaging (FMRI) detects focal MRI signal changes in
      brain tissue that are believed to result from changes in neuronal activity. We
      describe the dependence of this response in auditory cortex on the rate of
      presentation of simple speech stimuli. Speech syllables were presented to five
      normal subjects at rates ranging from 0.17 to 2.5 Hz, while the subjects
      performed a phoneme discrimination task. Regions studied with FMRI during this
      task included the lateral aspect of both temporal lobes. All subjects showed
      bilateral superior temporal lobe MRI signal increases that were coincident with
      stimulus presentation and performance of the task. The magnitude of this response
      increased in a monotonic, non-linear manner with increasing stimulus rate. This
      rate-response relationship was nearly identical in right and left hemispheres.
      The relationship may reflect metabolic activity integrated over time and subject
      to non-linear characteristics of neuronal recovery or blood flow regulation. The
      dependence of response magnitude on stimulation rate supports the hypothesis that
      the FMRI phenomenon indirectly reflects neuronal metabolic activity. The measures
      provided here should assist in the design of optimal activation strategies for
      the human auditory cortex.

PMID- 7812177
TI  - Associative ERP effects with memories of artificial faces.
AB  - A previous study (Valdes-Sosa and Bobes, 1990) described a negative ERP component
      evoked by mis-matches in a face-feature matching task, using photographs of real
      faces. This component could be N400 (or an analogue), elicited by associative
      priming within a non-linguistic domain: that of face structure. To confirm this
      it is necessary to demonstrate that semantic/linguistic recoding was not a
      necessary condition in triggering the negativity. This means falsifying what we
      call the 'priming by proxy' hypothesis, and locating the triggering mis-match
      within face structure. In this paper subjects studied artificial schematic faces
      over several sessions, and 1 week later were presented with a face-feature
      matching task with simultaneous ERP recording. Since no semantic information or
      verbal labels were available, eliciting a mis-match negativity with these faces
      contradicts the 'priming by proxy' hypothesis. In a first experiment, in which
      the subjects learning was controlled through a face familiarity decision task, no
      significant mis-match negativity was found. However, in a second experiment in
      which learning was controlled through a forced-choice face-feature match, a
      significant mis-match negativity was found in the subsequent recording session.
      This result supports the idea that a component similar to N400 can be elicited by
      an associative mis-match restricted to the face-structural domain.

PMID- 7812178
TI  - ERP amplitude and scalp distribution to target and novel events: effects of
      temporal order in young, middle-aged and older adults.
AB  - Event-related brain potentials (ERPs) were recorded from young (mean age = 24.1),
      middle-aged (48.7) and older (69.7) adults during a version of the oddball
      paradigm, in which 48 unique, unexpected novel stimuli were interspersed with
      equally rare instructed targets. As older relative to younger adults are thought
      to differ in their ability to inhibit the processing of task irrelevant
      information, we expected, based on previous work, that novel stimuli would retain
      their 'novelty' longer in older than in younger adults. To assess this, P3
      amplitude and scalp topography elicited by novels and targets were analyzed as a
      function of stimulus number (n = 6) within the block and as a function of block
      number (n = 4). The results were in line with the prediction: While the younger
      adults' P3 scalp distribution shifted from a relatively more frontal to a
      relatively more posterior focus as a function of novel number within the block,
      this was not evident in the scalp topographies of the older adults. Coupled with
      the older adults' elevated false alarm rates to novel stimuli, the data are
      consistent with a change in frontal lobe function with increases in age.

PMID- 7812179
TI  - Superior colliculus activity related to attention and to connotative stimulus
      meaning.
AB  - Single-and multi-unit activity was recorded from cells in the superior colliculus
      of two awake monkeys (Macaca fascicularis). 32.5% of 366 investigated units
      responded while the animals attentively gazed at visual stimuli. 50% of these
      neurons responded to all stimuli presented, including stationary and moving light
      bars, whereas the other neurons only responded to specific stimuli like faces or
      food. The responses of a part of these neurons depended on the connotative
      stimulus meaning.

PMID- 7812180
TI  - Cell suicide in the developing nervous system: a functional neural network model.
AB  - A computational model of programmed cell death (PCD) in the nervous system is
      described. A neurobiologically realisable method for identifying and removing the
      least useful cells from a network is developed, and it is shown by simulation
      that an artificial neural network can solve difficult problems efficiently if it
      is given more neurons initially than it needs subsequently. The least useful
      neurons die off gradually after learning is complete, and the learned solution
      can then be maintained with a smaller number of units than were needed for
      initial learning. The research suggests a functional role for PCD, and how self
      limiting PCD could be achieved in real neural systems.

PMID- 7812181
TI  - Neuropeptides, antagonists and cell proliferation: bombesin as an example.
AB  - A variety of studies has recently demonstrated that a group of peptides with
      relatively low molecular weights may play an important role in the rate of
      proliferation of tumor cells in vitro and in vivo. Among these peptides are
      bombesin and gastrin-releasing peptide (GRP) which both can function as autocrine
      growth factors in several neoplastic cells. These two neuropeptides also act as
      gut hormones and neuromediators. In this family of peptides, a shared C-terminal
      sequence is necessary for biological activity. The knowledge of this sequence
      provided a structural basis for the design of synthetic antagonists. Such agents
      are capable of interfering with the processing or the release of the autocrine
      growth factor or with its receptor, and might have a potential therapeutic
      utility. This short paper, focused on one class of neuropeptides, is not intended
      as an extensive review of this rapidly expanding field, but rather a survey of
      several topics presently under investigation.

PMID- 7812182
TI  - The Epstein-Barr virus BRLF1 gene product transactivates the murine and human c
      myc promoters.
AB  - A common feature of the Epstein-Barr virus (EBV)-associated malignancy, Burkitt's
      lymphoma, is chromosomal translocation affecting the c-myc oncogene. We report
      here that an EBV immediate-early (IE) protein, BRLF1 (R), transactivates the
      murine and human c-myc promoters. The R transactivator enhances expression from
      transiently transfected murine and human c-myc promoters as determined both at
      the CAT reporter and at the mRNA level. Transactivation of the human c-myc
      promoter by R occurs in several different cell lines, and this effect is reporter
      gene independent. Both the P1 and P2 c-myc promoters can be activated by the EBV
      R IE protein, although the R-induced transactivation of P1 is greater than P2.
      The portion of the human c-myc promoter from -228 to -63 (relative to the P1 mRNA
      start site) is necessary, but not sufficient, for transactivation by R in the
      Louckes B-cell line. Binding of the R protein directly to the c-myc promoter
      could not be demonstrated, suggesting that the effect of R on c-myc activity
      occurs by an indirect mechanism. The ability of an EBV protein to activate c-myc
      expression is likely to facilitate productive viral infection and is also
      potentially relevant in the genesis of EBV-associated lymphomas.

PMID- 7812183
TI  - Divergent effects of arachidonate and other free fatty acids on glucose
      stimulated insulin release from rat islets.
AB  - Long-term perifusion of isolated rat islets with 1 mM palmitate with 3 gm/dl
      albumin for 2 to 4 hrs. before an increase in glucose from 3 mM to 17 mM has been
      shown to suppress the stimulated release of insulin. In these studies, similar
      concentrations of myristate, stearate, oleate, palmitoleate, linoleate,
      linolenate, and gamma-linolenate had similar effects. Arachidonate, under similar
      conditions, enhanced rather than suppressed the release of insulin. This effect
      occurred at concentrations as low as 10 microM (lower than that needed for the
      suppressive effects of palmitate). This was not prevented by ibuprofen and was
      not associated with alteration of glucose oxidation. In prior work with
      palmitate, the fatty acid effects may have been due to suppressive effects of fat
      oxidation on glucose oxidation and signaling, but the arachidonate effects seen
      here may be due to metabolites or direct ionic effects.

PMID- 7812184
TI  - Protein distribution and gene expression of collagen type IV in the neonatal rat
      ovary during follicle formation.
AB  - Protein distribution and mRNA expression of basement membrane collagen (type IV)
      during follicle formation were studied using serial sections from 24, 48 and 72
      hrs. old rat ovaries. Collagen type IV, a protein found only in the basal lamina
      of the basement membrane, was localized under light microscope using a polyclonal
      antibody. During the first 24 hrs. postpartum, immunostaining was found as thin
      septa separating the clusters from the stroma. By 72 hrs. postpartum,
      immunostaining was found around each newly formed primordial follicle. The cell
      types involved in collagen type IV synthesis were determined by in situ
      hybridization using a biotinylated riboprobe. Before the follicles had been
      formed, the stromal cells showed intense staining while the epithelial
      presumptive granulosa cells showed a pale staining. However, after a follicle had
      been formed, some of the granulosa cells enclosed within the follicular basement
      membrane showed strong staining for the message. The presumptive granulosa cells
      are presumed to be the progenitors of granulosa cells. If so, these observations
      suggest that the expression of the message coding for collagen type IV by the
      granulosa cells may be a marker for commitment of the undifferentiated cell to
      the granulosa cell lineage.

PMID- 7812186
TI  - Quantitative and qualitative fluctuation of water in the mouse submandibular
      gland under secretagogue effect.
AB  - The short-term effects of two different secretagogues on the water contained in
      the mouse submandibular gland were studied using the thermal analysis as
      investigation method. Isoproterenol induced a retention while pilocarpine
      promoted a release of weakly and strongly bound water. In addition, submandibular
      glands of subjects administered with isoproterenol were characterized by a
      thermal behaviour different in males and females above all as concerns the time
      of reaction to the secretagogue; the reaction delay observed in females was
      correlated with the effects of this pharmacological substance on the convoluted
      granular tubules that are responsible for the sexual dimorphism in mice.

PMID- 7812187
TI  - Proteoglycan ultracytochemistry and conventional and high resolution scanning
      electron microscopy of vertebrate cerebellar parallel fiber presynaptic endings.
AB  - The parallel fiber "en passant" synaptic endings of mouse cerebellar molecular
      layer have shown by means of transmission electron microscopy, the presence of an
      electron dense extravesicular material in samples perfused with Alcian blue. This
      alcianophilic material was digested in cerebellar tissue previously treated with
      testicular hyaluronidase, suggesting the presence of hyaluronic acid or
      chondroitin 4- or 6-sulphate. Freeze-fractured Rhesus monkey cerebellar cortex
      prepared for conventional scanning electron microscopy also revealed the presence
      in fractured synaptic varicosities of parallel fibers of a high mass density
      material, in which the synaptic vesicles are embedded. Examination of
      cryofractured primate cerebellar cortex coated with thin chromium films, 1-2 nm
      thick, in the high resolution field emission scanning electron microscope showed
      the SE-I topographic contrast of an extravesicular material deposited in
      axoplasmic matrix of fractured parallel synaptic endings. The precise
      localization of this material corresponds to that observed in transmission
      electron microscopy and conventional freeze-fracture scanning electron
      microscopy. These electron microscopic findings tend to agree with the
      omnipresence in several vertebrates of a presynaptic axoplasmic material, which
      seems to be proteoglycan in nature.

PMID- 7812185
TI  - Chemical reagents of polypeptides side chain: relationships between solubility
      properties and ability to cross the inner mitochondrial membrane.
AB  - The correlation between the solubility properties of DCCD and EDAC (carboxyl
      specific groups reagents) and AI, NBD-Cl and TNM (tyrosyl specific reagents) and
      their efficiency to penetrate through the inner mitochondrial membrane, has been
      done. The penetration of the reagents was evaluated by using their ability to
      inactivate D-3-hydroxybutyrate dehydrogenase (EC 1.1.1.30) in its natural
      location, i.e. in intact mitochondria, or in its inverted location, i.e. in
      inside-out submitochondrial vesicles. For DCCD, AI, NBD-Cl and TNM there is a
      good correlation between the phase partition in octanol/water and the ability to
      cross or not the inner mitochondrial membrane. In contrast, there is a
      discrepancy for EDAC reagent which is hydrophilic, while it significantly
      inhibits BDH in intact mitochondria. The knowledge of the properties of these
      reagents can be very useful to locate strategic aminoacid residues in important
      biological functions.

PMID- 7812188
TI  - Viability of cryopreserved arterial wall: enzyme-histochemical and physiological
      markers.
AB  - Use of cryopreserved small-caliber arterial allografts for arterial bypass
      procedures has been suggested. In addition to immunological tolerance, long term
      in vivo success of these grafts may be dependent on the viability of arterial
      cells after cryopreservation. Metabolic and functional capabilities of arterial
      smooth muscle cells were evaluated by studying the enzyme histochemical
      expressions of sheep carotid arteries after various time of cryopreservation (7
      days, 90 to 150 days) and their contractile responses after freezing. The results
      indicated that cryopreserved arteries exhibited 4 features: (a) the enzyme
      activities were globally maintained, (b) the spontaneous endogenous oxido
      reduction (NitroBT test) was reduced, (c) contractile responses against KCl and
      norepinephrine were abolished, (d) metabolic status of frozen arteries was
      independent of the duration of cryopreservation. These data suggest that
      cryopreserved arterial muscle cells may be depleted in electron donors and/or
      energy-rich nucleotides substrates. This defect is present after short or long
      time of cryopreservation.

PMID- 7812189
TI  - Histoenzymatic study of human renal tissue preservation: II--Catalase activity in
      proximal tubular cells is uncorrelated with transplant evolution.
AB  - Enzyme histochemical activity of catalase, a peroxisomal enzyme involved in
      cellular antioxidant systems, was studied in proximal tubular cells of human
      renal transplants as a marker of ischemia-reperfusion injury in the prediction of
      the evolution of renal transplants. A low enzymatic activity was observed in all
      renal biopsies performed at 30 min. reperfusion with no difference between the
      several evolution types of renal transplants. Reduced catalase activity due to
      ischemia-reperfusion injury could not be correlated with renal function or used
      as an index of renal function recovery.

PMID- 7812190
TI  - Trichomonas vaginalis: repeated DNA target for highly sensitive and specific
      polymerase chain reaction diagnosis.
AB  - Trichomoniasis is recognised as a major sexually transmitted disease (STD) in the
      world and may act as an acquired immunodeficiency syndromes (AIDS) co-factor by
      enhancing the transmission of human immunodeficiency virus (HIV). Diagnosis of
      Trichomonas vaginalis can be achieved by several methods, but sensitive detection
      means are still lacking. In this study a 2000-bp repeated DNA fragment of T.
      vaginalis was cloned. Part of a conserved region of this insert was sequenced,
      two primers (TVK3 and TVK4) were chosen and a highly sensitive detection by
      polymerase chain reaction (PCR) was then developed for T. vaginalis. All strains
      of T. vaginalis analysed with these primers gave the expected 350-bp fragment and
      a 450-bp additional fragment. Sequence analysis of these PCR amplification
      products revealed that the 450-bp fragment contained the 350-bp with a 100-bp
      insertion characterised by a TGG microsatellite. A second primer set, namely TVK3
      and TVK7 (determined at the border of the insertion), yielded PCR products of
      expected sizes. After amplification we were able to detect a single parasite. We
      also detected T. vaginalis in vaginal fluids of patients with STD. There was no
      reaction with human DNA or other infectious agents. It appears that the two set
      primers are highly specific of T. vaginalis and provide a useful tool for PCR
      diagnosis in asymptomatic and symptomatic patients especially among the HIV at
      risk individuals.

PMID- 7812191
TI  - L-leucine transport systems in Saccharomyces cerevisiae participation of GAP1, S1
      and S2 transport systems.
AB  - L-leucine uptake in Saccharomyces cerevisiae is mediated by three different
      transport systems, S1, S2 and GAP1. Their activities are dependent on the
      nitrogen source of the culture media. Wild type cells grown in L-proline exhibit
      a single transport system with high affinity and high Vmax that is partially
      inhibited by L-citrulline. A gap1 mutant shows two transport systems with Km and
      Vmax values similar to those previously described as S1 and S2, this transport
      activity is not inhibited by D-leucine, D-isoleucine or D-valine. Two systems can
      be also determined in wild type cells grown in rich medium containing a mixed
      nitrogen source where decreased GAP1 function is observed. In either wild type or
      gap1 cells grown in medium containing ammonium ions as sole nitrogen source, L
      leucine uptake kinetics shows two systems with lower Vmax and similar Km values
      to those of the S1 and S2 systems. These results show that in S. cerevisiae GAP1,
      S1 and S2 participate in L-leucine entrance in cells grown in a poor nitrogen
      source, and that S1 and S2 are two ammonia-sensitive permeases that mediate the
      uptake in cells grown in a rich nitrogen source.

PMID- 7812192
TI  - Calcium dependent cellular uptake of a c-myc antisense oligonucleotide.
AB  - Because a major limitation of ODN (oligodeoxynucleotide) use is inefficient
      cellular uptake, methods to improve ODN uptake could have important implications
      in the investigational and possibly therapeutic use of ODNs. In this study,
      antisense c-myc ODN cellular uptake in elevated extracellular calcium was
      increased up to 48-fold in the four cell lines examined. The role of calcium in
      ODN cellular uptake was examined using a 21-base ODN complementary to the c-myc
      proto-oncogene and the Rauscher cells. Cells were pretreated with uptake
      inhibitors in either 1.8 (physiologic) or 5.4 mM calcium prior to addition of
      (32P) labelled ODN. In physiologic calcium conditions, ODN cellular uptake was
      partially dependent on cellular energy and a trypsin-sensitive surface protein.
      In contrast, in the presence of elevated (5.4 mM) extracellular calcium,
      trypsinization and metabolic inhibition had a reduced and no effect,
      respectively, on uptake. Endocytosis and lysosomotropic inhibitors did not
      decrease uptake in either calcium concentrations. Therefore, the mechanism of ODN
      uptake may depend on the level of extracellular calcium. Furthermore, surface
      binding accounted for approximately 60% of total uptake in both physiologic and
      elevated calcium concentrations, suggesting that the increased uptake was not due
      exclusively to increased surface binding. Thus, the predominant mechanism of ODN
      uptake may depend on the extracellular calcium concentration.

PMID- 7812193
TI  - Differential localization of type IV collagen in Bruch's membrane of the eye:
      comparison of two polyclonal antibodies.
AB  - The ultrastructural localization of type IV collagen in the basal lamina of the
      retinal pigment epithelium (RPE) and choriocapillary endothelium (CCE) of the rat
      eye was studied using a pre-embedding immunoperoxidase and a post-embedding
      immunogold method. Antibodies to type IV collagen from human placenta and from
      murine Engelbreth-Holm-Swarm (EHS) sarcoma were used with both methods. In the
      preembedding method, both antibodies were localized to the basal lamina of the
      RPE and CCE. In the postembedding method, antibody to EHS tumor collagen was also
      localized to both basal laminae. However, when the latter method was used with
      antibody to placental collagen, much less labeling was seen in the basal lamina
      of the RPE compared with that in the CCE. The findings suggest that in the basal
      lamina of the RPE (but not the CCE), the strongly immunogenic 7S domain of type
      IV collagen is inaccessible to antibodies directed against this protein. This
      effect may be due to masking of the 7S domain by other components or to a
      conformational change in the collagen molecule.

PMID- 7812194
TI  - The AML1 and ETO genes in acute myeloid leukemia with a t(8;21).
AB  - The translocation between chromosomes 8 and 21, t(8;21)(q22;q22), is the most
      frequent abnormality seen in approximately 46% of patients with acute myeloid
      leukemia with French-America-British (FAB)-M2 morphology and an aneuploid
      karyotype. The breakpoints in this translocation have been characterized at the
      molecular level, and the genes involved are AML1 on chromosome 21 and ETO (eight
      twenty one) on chromosome 8. AML1 has homology to the alpha subunit of the murine
      polyoma enhancer binding protein, pebp2, and to the segmentation gene, runt, of
      Drosophila melanogaster. ETO, also called MTG8 (myeloid translocation gene on 8)
      has no overall homology to known proteins, but it contains two DNA-binding zinc
      finger motifs and several regions that are proline- and serine-rich. Both AML1
      and ETO are thought to be transcription factors because the motifs they contain
      are found in other transcription factors. Both genes are transcribed from
      telomere to centromere, and cytogenetic analysis of variant translocations has
      shown that the critical junction always conserved is on the derivative 8
      chromosome. The rearrangement between the two chromosomes results in a fusion
      gene that contains the 5' region of AML1 including that homologous to runt fused
      to almost all of ETO. The fusion transcript from the der(8) chromosome is
      consistently detected in patients with the t(8;21). The translocation can be
      detected at the molecular level with selected genomic DNA probes from chromosome
      21 and from chromosome 8 near the breakpoint in 80-100% of the t(8;21) patients
      at diagnosis and in relapse, and with reverse transcriptase-polymerase chain
      reaction (RT-PCR) in all of the patients at diagnosis and in long-term remission.
      These results indicate that leukemic clones are still circulating in patients who
      have been in remission for as long as 8 years.

PMID- 7812195
TI  - The 5q- syndrome: a scientific and clinical update.
AB  - The 5q- syndrome is a subset of the myelodysplastic syndromes characterized by
      hypolobulated micromegakaryocytic hyperplasia and an interstitial deletion of the
      long arm of chromosome 5. In this concise review, we discuss the current
      understanding in regard to the genetic basis of the disorder and provide an
      updated clinical report on 43 patients with the disease who were seen at our
      institution.

PMID- 7812196
TI  - Allogeneic bone marrow transplantation in patients with myelodysplastic
      syndromes.
AB  - Myelodysplastic syndromes (MDS) represent an acquired group of clonal disorders
      of the pleuripotent stem cells, resulting in progressive life-threatening
      cytopenias or transformation into acute leukemias. A major issue of using alloBMT
      in MDS is the criteria used for patient selection. Therapeutic trials of lesser
      intensity such as differentiating agents, and cytokines could be the preferable
      choice for patients with good prognostic features. On the other hand, patients
      with poor prognostic features may urgently need to establish a normal
      hematopoiesis through allogeneic bone marrow transplantation (alloBMT). Important
      prognostic indicators in MDS include FAB classification, presence of abnormal
      localization of immature precursors, degree of cytopenias and cytogenetic
      abnormalities. We used a novel preparative regimen--"BAC" consisting of the
      consecutive administration of 1 mg/kg of busulfan every 6 hours for 16 doses
      followed by 2 g/M2 of cytosine arabinoside (ara-C) given every 12 hours for four
      doses, and finally 60 mg/kg of cyclophosphamide daily for 2 days. Thirty two
      patients transplanted had a median age of 33 years. Nine of the patients had
      either RA or RARS, 21 had RAEB or RAEB-T and 2 were unclassified MDS. Twenty two
      of our patients had chromosomal abnormalities while 10 had a normal karyotype
      analysis. Nine of the 32 patients had documented leukemic transformation and
      received induction therapy prior to BMT. The median time from diagnosis to BMT
      was 5.6 months, ranging from 1.3 to 30.2 months. Nineteen out of 32 patients are
      alive without disease, with a median follow up of 24 months. The actuarial event
      free survival for the entire group is 52%. Two patients have relapsed with an
      actuarial relapse rate of 12%. Only significant favorable prognostic indicator
      for the event-free survival was in the recipient of a genotypically matched graft
      (76%) compared to recipients of a non-genotypic graft (23%) (p = 0.02). "BAC" is
      a unique preparative regimen for alloBMT in MDS with excellent results.

PMID- 7812197
TI  - The increasing incidence of non-Hodgkin's lymphoma (NHL): the possible role of
      sunlight.
AB  - This review critically examines the rise in incidence in non-Hodgkin's Lymphoma
      (NHL) in selected parts of the world and concludes that much of the increase is
      likely to be due to unknown biological factors. It postulates that one reasonable
      explanation for the rise in incidence of NHL is the ever increasing exposure of
      populations, particularly in the Northern Hemisphere, to sunlight. Support for
      the hypothesis is supplied from both epidemiological evidence and studies of the
      responses of lymphocytes to ultra-violet light in both in vitro and in vivo
      experimental work.

PMID- 7812198
TI  - Hypercalcemia, parathyroid hormone-related protein expression and human T-cell
      leukemia virus infection.
AB  - Adult T-cell leukemia (ATL) associated with HTLV-1 infection is characterized by
      the development of hypercalcemia in over two thirds of patients. Dysregulation of
      cellular gene transcription by viral proteins is an emerging paradigm for
      molecular pathogenesis of disease. A recent example is the parathyroid hormone
      related protein (PTHrP) gene, which has been implicated in the hypercalcemia of
      ATL, and is transactivated by the HTLV-1 tax and HTLV-11 tax proteins. PTHrP is
      expressed at high levels in leukemia cells derived from ATL patients, as well as
      in asymptomatic HTLV-1 positive carriers. This article reviews the interaction of
      the HTLV-1 transcriptional regulator tax with the PTHrP promoter. Tax mediates
      its effects on PTHrP via cellular transcription factors AP-2 and AP-1, and
      transactivation via an AP-2 motif represents a novel interaction of tax with a
      cellular transcription factor.

PMID- 7812199
TI  - Differentiation therapy of myelodysplastic syndromes with retinoic acid.
AB  - Clinical trials of differentiation therapy on MDS with retinoic acid are
      reviewed, and it is discussed whether the differentiation therapy with this drug
      has scientific relevance for MDS. 13-Cis retinoic acid (13-CRA) may have moderate
      effect on 20-30% of patients with MDS. In general, the responses are short and
      toxicity is significant. Since the responses may take at least three weeks and
      sometimes several months to occur, only patients with a relatively indolent
      clinical course of MDS would be suitable candidates for this therapy. However, a
      placebo-controlled prospective randomized study could not confirm the
      effectiveness of this retinoic acid on MDS. There are only a few clinical trials
      of all-trans retinoic acid (ATRA) for treatment of MDS. ATRA may have a moderate
      effect on MDS, but no such a remarkable effect shown on acute promyelocytic
      leukemia. A placebo-controlled randomized study as having been conducted in 13
      CRA is definitely needed to confirm the effectiveness of ATRA on MDS.

PMID- 7812200
TI  - Non-Hodgkin's lymphoma and pregnancy.
AB  - Non-Hodgkin's lymphoma (NHL) is infrequently diagnosed during pregnancy. Most
      NHL's complicating pregnancy are aggressive and disseminated. This presentation
      together with the possible teratogenecity of diagnostic methods dictate a limited
      staging workup during pregnancy. Although prognosis had been reported to be poor,
      there is recent evidence to suggest that when properly treated, pregnancy does
      not affect the course of lymphoma. The risk to the fetus can also be reduced by
      an appropriate therapeutic approach.

PMID- 7812201
TI  - Cytogenetic abnormalities in B-immunoblastic lymphoma.
AB  - We have considered the cytogenetic abnormalities present in 27 unpublished cases
      of B-immunoblastic lymphoma. Among these 27 patients, the chromosome changes were
      heterogeneous and complex. The chromosomes most commonly gained were 3 (44% of
      cases), 18 (44%), 6 (30%) and 11 (30%). The most common structural abnormalities
      involved band 14q32 (26%), band 18q21 (15%) and bands 6q16-21 (19%). Study of
      these 27 immunoblastic lymphomas did not allow us to tentatively identify a
      common primary cytogenetic abnormality unique to B-immunoblastic lymphoma,
      however, a translocation at 14q32 may be the primary cytogenetic lesion in some
      of the cases. Rather, we have added to the number of abnormalities reported in
      immunoblastic lymphoma and in non-Hodgkin's lymphoma in general.

PMID- 7812202
TI  - Persistent clonal expansions of CD3+TCR gamma delta+ and CD3+TCR alpha beta+CD4
      CD8- lymphocytes associated with neutropenia.
AB  - This communication reports the clinical and cellular features of five elderly
      female patients with persistent moderate to severe neutropenia and concomitant
      relative expansions of CD3+TCR gamma delta+ (n = 4) or CD3+TCR alpha beta+CD4-CD8
      (n = 1) lymphocyte populations. In clinical terms, severe neutropenia was the
      main contributing factor to patient symptoms although two additionally had long
      standing histories of rheumatoid arthritis. The absolute lymphocyte counts did
      not exceed the normal upper limit in these patients, and morphologically the
      lymphocytes were not typically of large granular lymphocyte (LGL) type although
      LGL-associated BLT-esterase staining was consistently increased. Expression of NK
      associated (NKa) membrane determinants (CD16, CD56 and CD57) were variable but
      there was an apparent correlation between weak membrane CD8 and CD16 expression.
      DNA genotypic studies confirmed that the four CD3+TCR gamma delta+ cases were
      clonal in nature and add further support to an emerging impression that
      expansions of these lymphocyte subpopulations may frequently be clinically
      associated with autoimmune phenomena in general and neutropenia in particular.

PMID- 7812203
TI  - T lymphocyte subpopulations in patients with B-cell chronic lymphocyte leukaemia:
      relationship to infective episodes.
AB  - Patients with B-cell chronic lymphocytic leukaemia (B-CLL) have an increased
      susceptibility to infection. Quantitative abnormalities of T-cells have been
      previously reported in B-CLL, although the relationship between such
      abnormalities and the incidence of infection still remains to be established. We
      therefore enumerated lymphocyte subpopulations in 22 patients with B-CLL grouped
      according to the number of infective episodes in the previous three years. No
      significant differences were found between the patient groups and the mean number
      of T-cells subsets (helper, suppressor, suppressor-inducer and suppressor
      effector) or NK cells, but patients with frequent infections were found to have
      significantly higher CD5+ B-cell counts. Thus, we confirm that T-cell
      subpopulations are numerically altered in patients with B-CLL, but found that
      such changes are not predictive of susceptibility to infection. Our results
      however suggest that the malignant B-cells may exhibit immunosuppressive
      activity.

PMID- 7812204
TI  - Leukemia cutis in acute promyelocytic leukemia: report of three cases after
      treatment with all-trans retinoic acid.
AB  - Acute promyelocytic leukemia (APL) is a distinct form of acute myelogenous
      leukemia characterized by an abundant number of abnormal progranulocytes, a
      severe coagulopathy and a distinct chromosomal abnormality t(15;17). Recently all
      trans retinoic acid (ATRA) has been shown to induce complete remissions in APL.
      We report three patients with APL treated with ATRA, who at the time of relapse
      had leukemic infiltration of the skin (leukemia cutis), a manifestation which we
      had not seen previously in over 60 patients with APL treated with chemotherapy
      alone and has only rarely been reported in the literature. We hypothesize that
      ATRA treatment for APL may be associated with an increased incidence of
      extramedullary disease at the time of relapse, which may be mediated through an
      increase in expression of adhesion molecules. Careful observation for
      extramedullary relapses in patients treated with ATRA for APL will be needed to
      confirm our observation.

PMID- 7812206
TI  - Adult Burkitt's lymphoma: clinical and prognostic evaluation of 20 patients.
AB  - Burkitt's lymphoma (BL), a rapidly growing lymphoma, is recognized by its
      aggressive course, brief median survival, and low rates of long-term survival for
      patients. Several polychemotherapeutic approaches are utilized. Twenty adult
      patients with BL identified according to the Kiel classification were analysed
      retrospectively. Therapeutic modifications depended upon the different times of
      the diagnosis. Eight patients received the LSA2-L2 regimen, 11 patients were
      treated with third generation polychemotherapeutic regimens for high-grade non
      Hodgkin's lymphomas: F-MACHOP and MACOP-B, and 1 elderly patient was given the
      COP regimen. Of the 11 patients treated with cyclic conventional therapy (7 with
      F-MACHOP and 4 with MACOP-B), 8 achieved a complete response (CR). Of the 8
      patients who were given the LSA2-L2 protocol, 4 obtained a CR. One elderly
      patient treated with the COP regimen obtained a partial response. Early stage of
      disease, low levels of LDH, and the absence of bone marrow involvement were
      characteristics of patients with good prognoses. Effective conventional third
      generation polychemotherapy regimens (F-MACHOP and MACOP-B), normally used for
      high-grade non-Hodgkin's lymphomas, were equally effective for a large fraction
      of adults with BL. Furthermore, our study confirms the important role of LDH
      level, stage, and bone marrow involvement as prognostic factors in BL as well as
      the roles of tumor burden in the CR rate and relapse-free survival.

PMID- 7812205
TI  - Long term results of interferon treatment in hairy cell leukemia. Italian
      Cooperative Group of Hairy Cell Leukemia (ICGHCL).
AB  - Eighty nine of 104 patients with hairy cell leukemia (HCL), enrolled between 1985
      and 1987 in a multicenter prospective study on human lymphoblastoid IFN alpha-n1,
      were evaluable for long-term follow-up. The induction treatment, 3 MU/mq daily
      for a median of 5.7 months, produced a response of 93%, complete+partial response
      (CR+PR) = 80%, minor (MR) = 13%. Neither prior splenectomy nor pre-treatment
      variables were associated with the rate of response to IFN. However maintenance
      treatment of 3 MU/mq weekly given randomly had a slightly significant effect on
      failure free survival (FFS). Of the 43 patients who relapsed, 31/36 (86%)
      obtained a new response with IFN. No differences in FFS were recorded between
      first and second response. At the third induction 7/11 patients were treated
      again with IFN, 4/7 obtaining some response, but the FFS was significantly worse.
      The overall survival is still 85%. We conclude that (1) IFN should be used as
      chronic uninterrupted treatment for HCL, (2) reduced dosage is sufficient to
      prolong the disease free status and (3) continuous lymphoblastoid IFN
      administration seems not to be associated with the development of resistance to
      retreatment.

PMID- 7812207
TI  - IgG subclass levels in patients with B cell chronic lymphocytic leukaemia.
AB  - Patients with B-cell chronic lymphocytic leukaemia (BCLL) have low levels of
      serum IgG. In order to determine if this is a pan IgG deficiency or a selective
      suppression of one or more IgG subclasses, levels of IgG 1, 2, 3 and 4 in nine
      BCLL patients were determined and compared to those of nine age and sex matched
      controls. No significant differences were found in the levels of IgG1 and IgG2,
      but the patients were found to have significantly lower levels of IgG3 (p < 0.05)
      and IgG4 (p < 0.05). Selective deficiencies of these isotypes may explain the
      particular pattern of infection seen in BCLL patients.

PMID- 7812208
TI  - Prognostic factors and survival in non-Hodgkin's lymphomas: the experience of the
      Istituto Oncologico Romagnolo (IOR).
AB  - In an attempt to evaluate natural history, prognostic factors and survival, the
      data of 340 patients with NHL were collected. 267 patients were evaluable for the
      analysis of prognostic factors and survival. The tumor samples were reviewed and
      reclassified according to the Kiel classification. At completion, 180 patients
      were affected by low-grade (LG)-NHL and 87 patients had high-grade (HG)-NHL.
      Numerous potential prognostic factors were analysed in univariate and
      multivariate analyses. Globally 154 patients (57.4%) obtained complete remission
      (CR) and 65 patients (24.3%) partial remission (PR). The response rate was
      similar in LG and HG-NHL groups. 5-years survival was 52% for all patients (53%
      in LG-NHL and 44% in HG-NHL). Median survival was 62 months in LG-NHL and 38
      months in HG-NHL (p = n.s.). At the univariate analysis overall survival (OS) in
      LG-NHL was favourably influenced by age < 65 years (p = 0.004), performance
      status > 80 (p < 0.02), early clinical stage (p < 0.001), absence of systemic
      symptoms (p < 0.001), low serum LDH (p < 0.001) and achievement of CR (p <
      0.001), while in the HG-NHL only by age (p = 0.005) and achievement of CR (p <
      0.001). The multivariate analysis showed early clinical stage, low serum LDH,
      absence of systemic symptoms and achievement of CR as independent prognostic
      factors in LG-NHL and only achievement of CR in HG-NHL.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7812209
TI  - Combined surgery and chemotherapy in primary gastric non-Hodgkin's lymphoma: a
      retrospective study in sixty-six patients.
AB  - Sixty-six consecutive patients with primary gastric non-Hodgkin's lymphoma are
      reported. All patients underwent surgery which consisted of radical resection in
      23 patients (36%) and partial or palliative excision in the remaining 43 cases
      (36 and 7 respectively). Three patients died before starting chemotherapy, two
      refused the treatment and 61 completed the postoperative chemotherapeutic
      programme. We analysed this group of patients in order to assess the efficacy of
      chemotherapy following surgery. Chemotherapy included either CVP or the original
      protocols from our institution. Excluding patients who underwent radical
      resection, postoperative chemotherapy induced complete remission in 87% of the
      remaining 39 patients. After a median follow-up of 84 months (range 6-216), the
      10-year cause-specific survival was 90% with a stable curve plateau after about
      25 months. The survival was only influenced by response to therapy (p < 0.0001).
      The disease-free survival for patients who were not radically resected was 93%.
      We encountered only two relapses after 15 and 32 months. One of these was local
      and the other systemic. Our results indicate that chemotherapy following surgery
      induces long-term remission and survival in primary gastric lymphoma and in
      particular improves remission and survival, in stage II. In our opinion, surgery
      may also be fundamental for the treatment of gastric lymphoma in the majority of
      cases.

PMID- 7812210
TI  - Significance of circulating plasma cells in multiple myeloma.
AB  - The number of circulating plasma cells (CPC) was determined on mononuclear cell
      preparations after Giemsa (morphology) and light chain staining
      (immunocytochemistry). Both methods gave reproducible and identical results when
      CPC were 1% or more. Using this limit, no CPC were observed in MGUS (0/11) and
      primary amyloidosis (0/2), whereas 45/98 (45.9%) multiple myeloma (MM) pts had >
      or = 1% CPC. 3/14 pts (21.4%) in stage I, 5/13 pts (38.5%) in stage II, 20/28 pts
      (71.4%) in stage III, 4/25 pts (16%) at plateau phase, and 13/18 pts (72.2%) at
      relapse had > or = 1% CPC (p < 0.001). Mean beta-2 microglobulin was 3.77 mg/l
      and 6.08 mg/l for pts without or with > or = 1% CPC, respectively p = 0.0001).
      Presence of CPC was also correlated with an higher percentage of bone marrow PC,
      but not with the number of Ki-67 positive BM-PC, and not with CRP or LDH levels.
      K/L and Gamma/Alpha CPC isotype ratio showed these cells as monotypic in nearly
      all pts. The prognostic value could not really be assessed in this study, as only
      the initial response to therapy was investigated, and the latter failed to give
      any difference between pts with and without CPC. So, presence of CPC is not an
      infrequent finding, but is highly related to tumor mass and active disease; in
      most if not all patients they are monotypic and certainly belong to the malignant
      clone. Their prognostic value is unclear but under current investigation; CPC are
      correlated with B-2M level.

PMID- 7812211
TI  - Plasma cell acid phosphatase and prognosis in multiple myeloma.
AB  - The clinical significance of plasma cell acid phosphatase (PCAP) was evaluated in
      143 patients with monoclonal gammapathies, using a semiquantitative cytological
      scoring method. Significantly higher PCAP scores were measured in overt myelomas
      than in MGUS or in smouldering myelomas, during the phases of activity
      (diagnosis, progression, relapse), and in patients with extended disease. Among
      various clinical and laboratory parameters, PCAP was significantly related to the
      percentage of bone marrow plasma cells, the neoplastic growth fraction, as
      determined by Ki67 monoclonal antibody, and to serum levels of C-reactive
      protein. An inverse relationship was also found between PCAP and hemoglobin
      levels. Although the patients with "flaming" plasma cells exhibited low PCAP
      scores and poor prognosis, on the whole, myeloma patients with PCAP scores < 200
      showed a significantly longer median overall survival than those with PCAP > 200
      (46 vs 20 months, p < 0.003). However, in the multivariate analysis, beta 2
      microglobulin, growth fraction, performance status, and serum levels of thymidine
      kinase and C-reactive protein, but not PCAP, maintained a significant prognostic
      relevance. In conclusion, although PCAP may be considered a marker of disease
      activity, other parameters provide better prognostic information in myeloma
      patients.

PMID- 7812212
TI  - All-trans retinoic acid and induction of apoptosis in acute promyelocytic
      leukemia cells.
AB  - All-trans retinoic acid (ATRA) represents a highly effective treatment for acute
      promyelocytic leukemia (M3-ANLL). This compound induces the leukemic
      promyelocytes to differentiate into morphologically and phenotypically mature
      myeloid cells. The mechanism of action of ATRA is far from fully understood. It
      has recently been reported that, along with its differentiation activity, ATRA
      causes apoptosis in the acute promyelocytic leukemia cell line HL-60. In this
      study we attempted to test whether ATRA is also able to induce apoptosis in fresh
      leukemic cells from M3-ANLL patients. Our results indicated that although
      morphological differentiation was detectable in 9/9 M3-ANLL samples after in
      vitro exposure to ATRA 10(-6) M, the percentage of apoptotic cells in the treated
      samples did not significantly differ from that obtained in controls (13.1% vs
      9.4% respectively, after 8 days exposure). These data suggest that apoptosis does
      not seem to be the key mechanism by which ATRA exerts its action in M3-ANLL, at
      least at the blast cell level.

PMID- 7812213
TI  - Autoreactive T cell-dependent polyclonal hypergammaglobulinemia in mantle cell
      lymphoma.
AB  - We investigated the mechanism of polyclonal B cell differentiation in mantle cell
      lymphoma (MCL) using peripheral blood mononuclear cells (PBMC) from a patient
      with MCL in leukemic stage presenting polyclonal hypergammaglobulinemia. Patient
      T cells not only responded to autologous non-T cells but induced polyclonal
      production of IgG in vitro. Flow cytometric analysis of PBMC showed the increased
      conversion of CD4+ T cells from the naive to the memory state. We propose the
      possible mechanism that autoreactive T cells may be involved in polyclonal B cell
      differentiation in this monoclonal B cell disorder.

PMID- 7812214
TI  - Immunoglobulin light chain restriction and clonal rearrangement in nodular
      paragranuloma.
AB  - B-cell clonality was demonstrated in a typical nodular paragranuloma case (NP) by
      both immunoglobulin (Ig) surface analysis and Ig genes rearrangement studies. On
      frozen sections, immunostaining for Ig light chain expression revealed a clear
      cut predominance of Ig lambda-expressing cells, recognizable as both small
      lymphocytes and lympho-histiocytic (L&H) cells. Accordingly, molecular analysis
      of the Ig genes showed a monoclonal rearrangement of the lambda chain gene,
      although no specific pattern of heavy chain gene rearrangement could be detected
      by JH analysis. The C lambda rearranged band was identified with two different
      restriction enzymes, excluding the hypothesis of a genomic polymorphism.
      Furthermore, the C kappa gene was almost completely deleted, indicating that the
      developmental hierarchy of Ig genes rearrangement has been respected. The
      molecular pattern of the C lambda hybridizing band was consistent with
      monoallelic rearrangement of almost the entire DNA sample, indicating that clonal
      proliferation was not limited to L&H cells, but also involved surrounding
      lymphocytes. This finding is in keeping with the immunohistochemical evidence of
      a lambda light chain restriction on both L&H cells and small lymphocytes,
      pointing to a close relationship between these two cell types. Our results as a
      whole suggest that L&H cells and B lymphocytes share a common origin and may both
      be involved in clonal proliferation in NP.

PMID- 7812215
TI  - A patient with primary hypoparathyroidism developing hypercalcemia associated
      with adult T-cell leukemia/lymphoma.
AB  - A 38-year-old woman was admitted to our hospital with symptoms and signs of
      hypocalcemia in 1977 and a diagnosis of primary hypoparathyroidism was made with
      a positive Ellsworth Howard test. She was then lost to follow up until 1992 when
      she returned this time with symptoms and signs of hypercalcemia. An inguinal
      lymph node was biopsied showing non-Hodgkin's lymphoma, diffuse pleomorphic type
      and monoclonal integration of proviral human T-cell lymphotropic virus-1 DNA was
      detected in lymph node cells indicating ATLL. Serum parathyroid hormone-related
      peptide (PTHrP) was slightly elevated and the tumor cells were positively stained
      with anti-PTHrP serum. Combination chemotherapy with vincristine, adriamycin,
      cyclophosphamide and prednisolone was given to the patient with disappearance of
      the lymphadenopathy and subsequent normalization of PTHrP levels. Interestingly,
      the signs and symptoms of hypocalcemia reappeared after the treatment requiring
      replacement therapy with calcium and vitamin D.

PMID- 7812218
TI  - Localization and diffusion of glucagon receptor in rat hepatocytes.
AB  - The lateral diffusion rate of glucagon receptor in rat hepatocyte plasma membrane
      in the absence and presence of glucagon was measured to be approximately 7.0 x
      10(-10) cm2/s. The percentage of glucagon receptor molecules remaining on the
      cell surface after the activation of signal transduction process by 100 nM
      glucagon was approximately 74% of its original number. Although the number of
      glucagon receptors on the plasma membrane capable of interacting with its signal
      transduction partners decreases on addition of glucagon, the lateral diffusion
      rate and the percentage of mobile receptors remain essentially unchanged. A
      hypothesis has been developed that for signal transduction to occur, the random
      diffusion-dependent collision of one, two, or all three components is an
      essential part, and it may be the rate-limiting step. An approximate calculation
      has been made of random diffusion-dependent theoretical and experimental
      collision frequencies using experimentally measured concentrations and reasonable
      value for diffusion rate of G protein to investigate the role of diffusion in
      signal transduction. These calculations indicate that the diffusion of individual
      components is important and may be the rate-limiting step in the signal
      transduction process. The diffusion rate and percent mobile fraction of glucagon
      receptor data presented in this article are the first step toward elucidating the
      validity of the diffusion-dependent signal transduction hypothesis.

PMID- 7812216
TI  - Quantitative determination of recombinant fibroblast growth factor receptor in
      baculovirus-infected insect cell cultures.
AB  - Members of the fibroblast growth factor protein family are involved in several
      biologically important processes, including angiogenesis, wound healing, and
      tumor growth and metastasis. Interactions of basic fibroblast growth factor
      (bFGF) and its receptors are of considerable pharmacological importance. Attempts
      were made to produce gram quantities of a soluble extracellular form of basic
      fibroblast growth factor receptor type 1 (bFGFR1) in order to study the
      energetics of its interaction with bFGF. The aim of the present study was to
      develop a method for monitoring changes in concentration of bFGFR1 during its
      production by large-scale baculovirus-infected insect cell culture. A simple
      reverse-phase high-performance liquid chromatographic assay was developed for
      direct determination of the soluble receptor secreted into insect cell-culture
      media. The method permitted cell-culture samples containing varying amounts of
      fetal calf serum and bFGFR1 (10-30 mg/L) to be analyzed without prior
      purification. The assay was linear for added receptor in the range of 1-7
      micrograms.

PMID- 7812217
TI  - Dioxin-dependent, DNA sequence-specific binding of a multiprotein complex
      containing the Ah receptor.
AB  - Fractionation of rat liver cytosol, using as an affinity reagent the DNA
      recognition sequence for the liganded aromatic hydrocarbon (Ah) receptor,
      enriches for proteins that are about 110, 106, 98/96, 57, and 54 kDa in size. The
      proteins display 2,3,7,8-tetrachlorodibenzo-p-dioxin-dependent, DNA sequence
      specific binding that is characteristic of the liganded Ah receptor.
      Immunological studies imply: 1. That the 98/96-kDa protein is the Ah receptor
      nuclear translocator (Arnt); 2. That the 110- and 106-kDa proteins are not
      immunologically related either to each other or to Arnt; and 3. That the 110-,
      the 106-kDa, and the Arnt proteins are members of a multicomponent protein
      complex. cDNA cloning studies indicate that the 106-kDa protein is the rat Ah
      receptor. The N-terminal 384 amino acids of the rat receptor show substantial
      sequence homology to the mouse and human Ah receptor. The sequence conservation
      across species imputes functional importance to this region of the receptor. In
      contrast, the remainder of the protein is substantially less well conserved among
      rat, mouse, and human. The tissue distribution of Ah receptor mRNA is consistent
      with previous studies of the distribution of the receptor protein. Our findings
      demonstrate the use of DNA recognition site chromatography for purification of
      the Ah receptor and imply that the ligand receptor binds to DNA as part of a
      multiprotein complex.

PMID- 7812219
TI  - Expression of alpha 2-adrenergic receptor genes in rat tissues.
AB  - Alpha-2 adrenergic receptor subtypes are coded for by three genes.
      Pharmacologically alpha 2 adrenergic receptors can be classified into four
      subtypes: alpha 2A, alpha 2B, alpha 2C, and alpha 2D. Although pharmacologically
      distinct, the amino acid sequences of the alpha 2A and alpha 2D subtypes are
      approx 90% identical and have not been detected in a single species. Thus, they
      should be considered species orthologs and may be referred to as alpha 2A/D. The
      tissue distribution of the mRNAs for the rat alpha 2A/D, alpha 2B, and alpha 2C
      was analyzed utilizing RNase protection assays with probes directed to the third
      cytoplasmic loops. Alpha-2 adrenergic receptor mRNA was found in all tissues
      tested. Kidney, brain, and spinal cord had transcripts for all three subtypes.
      Only one mRNA subtype was detected in several tissues. Aorta and spleen had only
      alpha 2A/D mRNA, whereas heart and liver had only alpha 2B mRNA. All other
      tissues had two alpha 2 adrenergic subtype transcripts present. In contrast to
      the rat CNS, which contains predominantly alpha 2A/D and alpha 2C mRNA with
      little alpha 2B mRNA, peripheral tissues contain predominantly alpha 2A/D and
      alpha 2B mRNA with little alpha 2C mRNA.

PMID- 7812220
TI  - Biopsychosocial dentistry: the interface with psychiatric assessment.

PMID- 7812221
TI  - Histologic characteristics of the lateral pterygoid muscle insertion to the
      temporomandibular joint.
AB  - This study used low-power light microscopy to examine the histologic organization
      of the lateral pterygoid muscle interface with the temporomandibular joint. The
      sample included parasagittal sections of 20 intact temporomandibular joints from
      young adults (mean age 26.2 years) at autopsy. The lateral pterygoid muscle
      showed no consistent divisions into separate anatomic muscle heads at the
      insertion. The muscle fibers attached to the pterygoid fovea of the condyle
      immediately inferior to the articular surface in all cases. Some additional
      fibers inserted superiorly into the more anterior part of the articular disc in a
      minority of cases (31%). Fibers inserting into the disc represented only 2.4% to
      6% of the total superior-inferior length of the muscle insertion. It is
      hypothesized that the muscular force exerted by these few fibers inserting into
      the disc would not be sufficient to displace the disc anteriorly to the condyle.
      There were two histologic types of insertion of the lateral pterygoid muscle to
      the condyle. The superior part of the insertion was characterized by an
      identifiable tendon inserting through fibrocartilage. In the inferior part of the
      insertion, the muscle attached to periosteum without an obvious tendon. The
      presence of this tendon must be recognized in interpretation of soft tissue
      temporomandibular joint imaging.

PMID- 7812222
TI  - Effect of tooth clenching and jaw opening on pain-pressure thresholds in the
      human jaw muscles.
AB  - The measurement of the pain-pressure threshold in the human jaw muscles may be
      affected by variables such as the size of the pressure-transducer recording
      surface and the rate of applied pressure. The jaw muscles have a complex
      architecture that results in changes in muscle stiffness and compliance when
      different motor tasks are performed. Such changes in the jaw muscles are likely
      to affect the pain-pressure threshold. The central motor program associated with
      different tasks may also affect the pain-pressure threshold. A pressure algometer
      was used to measure the pain-pressure threshold in various regions of the
      masseter and temporalis muscles at different magnitudes of tooth clenching and
      jaw gape. The pain-pressure threshold increased at all recording sites as muscle
      contraction associated with tooth clenching increased. The pain-pressure
      threshold was not affected when the jaw gape changed. There were no apparent
      regional differences in pain-pressure thresholds in the masseter or temporalis
      muscles at different amounts of tooth clenching or jaw gapes. Pain-pressure
      thresholds were consistently higher in the temporalis muscle. When quantitative
      measures of jaw muscle pain-pressure thresholds are planned, the nature of the
      motor task should be controlled.

PMID- 7812223
TI  - The influence of time, facial side, and location on pain-pressure thresholds in
      chronic myogenous temporomandibular disorder.
AB  - This study examined masseter and temporalis pain-pressure thresholds in 29
      patients with chronic bilateral myogenous temporomandibular disorder and in 11
      controls. Patients with evidence of temporomandibular joint pathosis were
      omitted. The influence of time, facial side, muscle site, and side of greatest
      spontaneous pain on pain-pressure thresholds was measured. No significant pain
      pressure threshold differences were found between the more and less painful
      sides, as indicated by the patients, which lends support to theories of centrally
      mediated pain. Mean pain-pressure thresholds in patients differed over the four
      sessions, which is consistent with recent reports of fluctuating levels of pain
      in patients with temporomandibular disorders. Additional findings included
      significant pain-pressure threshold differences among muscle sites in patients
      and controls, and lower patient pain-pressure thresholds relative to controls.
      Within- and between-session reliability was adequate for patients (r = .85 and r
      = .75, respectively) and controls (r = .90 and r = .75, respectively).

PMID- 7812224
TI  - A system for analysis of sleep and nocturnal activity in craniomandibular
      muscles.
AB  - A system was developed for continuous, full-night, polysomnographic recording of
      sleep using manual sleep scoring and automatic electromyographic analysis of
      craniomandibular muscle activity. In the sleep laboratory, data are stored on
      tape with hard copy on paper followed by off-line, computer-controlled digital
      processing. Muscle activity is described by the Amplitude Probability
      Distribution Function and by parameters of time and intensity. Sleep and
      electromyographic data are available graphically on screen, and the results are
      presented in tables and graphics after statistical treatment. The system was
      developed to provide a differentiated, detailed analysis of sleep and nocturnal
      muscle activity in the craniomandibular system that is suitable for comparing
      groups of individuals, effects of treatments, and physical load of muscles.
      Applications of the system are demonstrated.

PMID- 7812226
TI  - Litigation and chronic facial pain.
AB  - Clinical studies have suggested that the presence of litigation in chronic pain
      syndromes may complicate diagnostic and treatment strategies. In addition,
      psychosocial factors may be prevalent in such cases. The present study explored
      the possible correlation in the facial pain population between patients in
      litigation and psychological disturbance as measured by the Minnesota Multiphasic
      Personality Inventory. Beck Depression Inventory and Wahler Symptom Checklist
      scores also were compared. One hundred eleven patients diagnosed with chronic
      facial pain were asked if they currently were involved in litigation related to
      their medical complaints. The result revealed that 18% of the 111 patients were
      in litigation at the time of their initial visit. The Minnesota Multiphasic
      Personality Inventory profiles showed that 45% of the litigation patients had
      four or more clinical scales above 70 (significantly elevated) on the Minnesota
      Multiphasic Personality Inventory. In contrast, only 18% of the patients who were
      not in litigation had four or more scales above the 70 criteria. Beck and Wahler
      scores also were more elevated for the litigation group. The results of the study
      indicate that chronic facial pain patients in litigation may present with more
      psychological disturbance as compared to those patients not in litigation.

PMID- 7812225
TI  - Thermographic assessment of craniomandibular disorders: diagnostic interpretation
      versus temperature measurement analysis.
AB  - This study assessed electronic thermography as a diagnostic alternative for
      evaluation of temporomandibular disorders. The study populations consisted of 50
      temporomandibular joint patients having internal derangement or osteoarthrosis
      and 30 normal temporomandibular joint subjects. An Agema 870 thermovision unit
      was used for analysis. Diagnostic evaluations by expert interpreters were made
      using standard procedures. Thermography measurements included mean absolute
      temperature measurements and right-left temperature differences for five anatomic
      zones and four spot areas. Statistical analysis of data included both linear
      discriminant analysis and classification-tree analysis. Results indicated that
      when differentiating between "abnormal" and "normal" temporomandibular joints
      using classification-tree analysis, correct classifications were made in 89% of
      the cases and observer diagnostic accuracy was 84%. When evaluating for specific
      diagnoses (eg, osteoarthrosis, internal derangement, or normal temporomandibular
      joint), correct classifications using classification-tree analysis were made in
      73% of the cases and observer evaluation was correct in 59%. The three best
      temperature measures found were: (1) delta T of the zone immediately overlying
      the temporomandibular joint; (2) the zone temperature of the half-face; and (3)
      the spot temperature anterior to the external auditory meatus. Additional studies
      are needed before thermographic diagnosis of craniomandibular disorders is
      accepted clinically.

PMID- 7812227
TI  - Ear, nose, and throat symptoms in patients with TMD: the association of symptoms
      according to severity of arthropathy.
AB  - The association of the severity of temporomandibular arthropathy to ear, nose,
      and throat symptoms in patients with temporomandibular disorders has been poorly
      investigated in spite of its importance in clinical practice. The aim of this
      study was to see whether persons with more severe arthropathy have more ear,
      nose, and throat symptoms. Anamnestic and clinical evaluations were obtained at
      admission for 815 subjects with signs and symptoms of temporomandibular disorders
      of arthrogenic origin in physical tests. The severity of arthropathy was
      evaluated by a clinical index scoring joint sounds, tenderness to
      temporomandibular palpation, and pain severity in the temporomandibular joint
      region. Univariate analysis showed that the severity of arthropathy was
      significantly associated with ear, nose, and throat symptoms as a whole (P <
      .001) and specifically with deafness (P < .001) and dizziness (P < .05); however,
      tinnitus and earache were not statistically significantly associated. Multiple
      analysis showed deafness to be the only ear, nose, and throat variable
      independently associated with severity of arthropathy (P < .01). These findings
      lead to the conclusion that there is a considerable association between
      temporomandibular disorders of arthrogenic origin and ear, nose, and throat
      symptoms, especially deafness. They also suggest that further investigations
      should be done to compare the specific roles of craniocervical arthritis versus
      temporomandibular disorders in the etiology of ear, nose, and throat symptoms
      related to craniomandibular and craniocervical joint involvement.

PMID- 7812228
TI  - Appropriate use of predictive values in clinical decision making and evaluating
      diagnostic tests for TMD.
AB  - Temporomandibular disorder literature contains serious misunderstandings and
      misapplications of statistical concepts, including predictive values, in
      evaluating diagnostic modalities and in clinical decision making. The use of
      general population prevalence data for temporomandibular disorders to evaluate
      positive predictive values of diagnostic modalities is shown to be invalid. The
      positive predictive value of a diagnostic tool should not be used to evaluate the
      efficacy of the tool or to confirm the presence of temporomandibular disorders
      when the pretest likelihood of temporomandibular disorder is low (eg, 10%). In
      such a situation, the TMJ Scale's negative predictive value of 98% supports the
      dentist's clinical impression of the absence of temporomandibular disorders. When
      the pretest likelihood of TMD is high (eg, 90%), the TMJ Scale's positive
      predictive value of 97% supports the dentist's clinical impression of the
      presence of temporomandibular disorders. The predictive values of the subscales
      of the TMJ Scale that measure joint dysfunction and stress may be used to further
      refine the diagnostic impression. When the dentist is unsure of the presence of
      TMD and makes a pretest estimate of 50%, the TMJ Scale's positive predictive
      value of 81% and negative predictive value of 83% substantially improve the
      accuracy of clinical decisions.

PMID- 7812229
TI  - Effectiveness of conservative treatment for craniomandibular disorders: a 2-year
      longitudinal study.
AB  - The severity of symptoms of craniomandibular disorders was studied during a 2
      year period in 195 patients treated with conservative therapeutic schemes.
      Results revealed a continuing improvement and a statistically significant
      tendency for the great majority of patients to become asymptomatic or show a
      decrease in the severity of symptoms. By the end of the 2 years, 66.7% of the
      patients were symptom free, 25.6% presented with slight symptomatology, and 3.1%
      were recorded with a fluctuating recurrence of symptoms. This investigation
      provided the data to develop an exponential model for the hypothesis that
      stabilization of effectiveness of conservative treatment is achieved between 6
      months and 1 year after the initiation of treatment.

PMID- 7812230
TI  - The reproducibility of condylar hinge axis positions in patients, by different
      operators, using the electronic mandibular position indicator.
AB  - Three operators each made five recordings from 15 symptomatic patients using the
      electronic mandibular position indicator. The method consisted of measuring
      bilateral spatial changes of the hinge axis recalculated by the computer to an
      intercondylar distance of 110 mm and a third position, calculated from the
      rotation of the hinge axis, at the incisal guidance table. All individual patient
      recordings were related to the origin of the same coordinate system. This origin
      is designated and defined as the reference position, with purposeful elimination
      of any stated joint position for this definition. The measurements were in all
      planes of space at 10-millimicron increments, including the rotation of the
      transverse hinge axis in hundredths of degrees. These data showed that the
      reproducibility of hinge axis positions, ie, reference positions, to hinge axis
      condylar positions dictated by the maximum intercuspation of teeth was in average
      less than 0.2 mm for each record from all operators and patients.

PMID- 7812231
TI  - Evidence-based medicine.

PMID- 7812232
TI  - Committee to Advise on Tropical Medicine and Travel (CATMAT). Statement on
      travellers and HIV/AIDS.

PMID- 7812233
TI  - Committee to Advise on Tropical Medicine and Travel (CATMAT). Statement on
      travellers' diarrhea.

PMID- 7812235
TI  - Human plague in India, August-October, 1994.
AB  - As of 9 October, the total number of fatalities in India due to plague was 55 (52
      from Surat city and 3 from New Delhi). Reasons for the low case-fatality ratio
      remain to be determined and will require more detailed and reliable clinical and
      laboratory information. Additional studies into the patterns of transmission in
      the infected areas are underway or anticipated. By 14 October reports of both
      suspect and confirmed cases had decreased. The area around the Beed district in
      the state of Maharashtra was also declared as "infected" under the definition of
      the International Health Regulations. A WHO expert committee has been in the
      affected areas and detailed reports are anticipated.

PMID- 7812234
TI  - 1993-1994 influenza season: Canadian laboratory diagnoses, strain
      characterization and post-season serosurvey (Ontario).
AB  - In Canada as a whole, influenza A/Beijing/32/92-like virus was the dominant
      infecting strain in the 1993-1994 season with reported laboratory diagnoses
      peaking in January 1994. Vaccination is again urged for all persons in high-risk
      groups. Antibody induced by vaccination does not persist well from season to
      season and the emerging A/Shangdong/9/93 (H3N2)-like variant is related to
      A/Beijing/32/92(H3N2) but is inhibited less by antibodies to that strain.
      Conditions are also consistent with possible increased influenza B activity this
      season.

PMID- 7812236
TI  - Influenza in Canada, 1993-1994 season.

PMID- 7812237
TI  - Genetic DNA probes for Mycobacterium avium complex identification.
AB  - The acridinium ester labelled DNA probe specific for M. avium complex (MAC) was
      used for testing 30 strains of MAC previously identified by conventional
      procedures. The hybridization was positive in 26 strains, negative in 3 strains
      and one strain seemed to be contaminated when subcultured. The specific DNA
      probes allow to identify even the slow growing mycobacterial strains, in positive
      samples, within two hours while conventional methods usually take several weeks
      to show the result. A rapid confirmation of a mycobacterial species is invaluable
      for selecting an effective treatment as early as possible, which is extremely
      important e.g. in immunosuppressed patients, children with lymphadenitis, etc.
      Nevertheless, this method has the disadvantage of being too expensive for some
      laboratories, though questionable if repeated subcultures, technician's time and
      the delay in obtaining results are taken into account, and enabling to identify
      only a limited number of clinically significant mycobacterial species using
      commercially available probes.

PMID- 7812238
TI  - The influence of experimental liver injury on the activity of antigen-induced
      suppressor cells in murine spleen.
AB  - The authors investigated in CBA mice the suppressor cell formation in spleen,
      induced by injection of a supraoptimal dose of sheep red blood cells and assessed
      their activity in a passive transfer experiment in animals with liver injury,
      caused by carbon tetrachloride treatment. The influence of liver explants from
      mice, treated with carbon tetrachloride, on antigen-induced cells, cultivated
      together in diffusion chambers, was also studied. It was shown that carbon
      tetrachloride administration inhibited the antigen-induced suppressor cells
      formation in murine spleen. Splenocytes, containing antigen-induced suppressor
      cells from mice treated with carbon tetrachloride, transferred to syngeneic mice
      together with an immunogeneic dose of sheep red blood cells, caused a smaller
      decrease of the number of antibody-forming cells in the spleen of recipients than
      cells from normal mice. The liver explant damaged by carbon tetrachloride,
      influenced splenocytes, containing antigen-induced suppressor cells (AISC). This
      influence depended on the degree of liver injury. These data demonstrate the role
      of liver injury modifying the suppressor activity of splenocytes. The decrease of
      suppressor cell activity may be one of the mechanisms of enhanced antibody
      formation in patients with liver diseases.

PMID- 7812239
TI  - Serodiagnosis of cercarial dermatitis with antigens of Trichobilharzia szidati
      and Schistosoma mansoni.
AB  - In patients with parasitologically revealed dermatitis caused by cercariae of
      avian schistosomes (Trichobilhariza szidati) diagnostic indirect
      immunofluorescence technique (IFAT) was employed for the detection of antibodies.
      The efficacy of antigens prepared from cercariae of T. szidati and Schistosoma
      mansoni was tested in serodiagnosis. The results have shown that antigen of T.
      szidati is more reactive with the sera of patients than that of S. mansoni: the
      antibodies were detected already 3 days after penetration of cercariae, contrary
      to 10 days after penetration of avian schistosomes when antigen of S. mansoni was
      used. The results were confirmed with enzyme-linked immunosorbent assay (ELISA)
      and IFAT techniques in SPF mice (Mus musculus) experimentally infected with
      cercariae of T. szidati and S. mansoni or with fractions isolated from cercariae
      of T. szidati.

PMID- 7812240
TI  - Eradication of poliomyelitis in Bulgaria--problem encountered.
AB  - The authors analyze the effectiveness of the National Vaccination Programme with
      regard to poliomyelitis eradication in Bulgaria and the difficulties encountered
      in the 1980s and at the beginning of the 1990s. An account is presented on the
      eradication achieved, interrupted by an outbreak of 46 cases in 1991. The
      critical analysis points out the negative influence of several factors, disrupted
      by the failure in 1991. Based on these fact conclusions are drawn on a
      prolongation of the period needed to achieve the Eradication Programme goal. The
      main reasons for the delay are as follows: the intensive migration process, the
      existence of small non-immunized groups of population (gipsy population) as well
      as some shortcomings in the organization of the health services. According to the
      authors, stricter epidemiologic supervision is imperative for the country as well
      as coordination of similar approach to the problem in countries of the region.

PMID- 7812241
TI  - Human health and the environment in eastern and central Europe. Report of the
      conference Prague, Czech Republic, 12-15 April 1993.
AB  - A group of 46 leading environmental health scientists from 15 nations unanimously
      agreed to join forces in a new scientific effort to protect human health around
      the world from the potentially harmful effects of environmental chemicals and
      radioactive materials. The scientists agreed to establish a non-political
      European-based, not-for-profit organization whose objectives will be to promote,
      coordinate and fund environmental health research in order to provide a
      scientific basis for environmental remediation. The organization will be
      affiliated with the Conte Institute. The research priorities decided upon for
      Eastern and Central Europe were as follows: 1. Research into the effects of toxic
      metals, such as lead, cadmium, arsenic, and beryllium. 2. Research in the
      populations of the region on cancer, birth defects, and other diseases, with
      emphasis on data sharing across national boundaries, on quality control, and on
      use of biomarkers of reproductive and other effects. 3. Studies on the molecular,
      biochemical, and chromosomal bases for varying genetic susceptibilities to
      environmentally-induced diseases. 4. Coordination of research on radiation
      effects, especially on radiation-exposures resulting from nuclear power and
      weapons plants. 5. Research on approaches to bioremediation. 6. Education and
      training of professionals and nonprofessionals in environmental health issues, on
      an international basis. These and other issues will be taken up over time by this
      new, cooperative scientific research organization, as decided at the Prague
      Conference.

PMID- 7812242
TI  - History and development of public health care in Bohemia.
AB  - Following the introductory informative consideration of the conception of public
      health in different countries, the author quotes the first reports on public
      health service in the history of the "Kingdom of Bohemia". In the following text
      he considers the development of this service, emphasizes the role of the National
      Institute of Public Health and gives a survey of its brief history until its
      reestablishment on January 1, 1992.

PMID- 7812243
TI  - New serovars of Plesiomonas shigelloides 1992.
AB  - Fourteen new O (O77-O9O) and 4 new H (H42-H45) antigens were described. Seven O
      and 2 new H antigens were revealed among strains not agglutinating with antisera
      against 76 O and 41 H officially recognized serovars. The most frequent was
      serovar O80:H38 which was isolated in 5 countries (Sweden, Czechoslovakia,
      Bulgaria, Yugoslavia and Canada) from human material and from sewage and surface
      water.

PMID- 7812244
TI  - Epidemiology and spectrum of vibrio diarrheas in the lower cross river basin of
      Nigeria.
AB  - In 1991 a cholera epidemic occurred in Nigeria. The features of this cholera
      outbreak in a single hospital in Cross River, Nigeria, were examined.
      Microbiologic techniques included the use of thiosulphate citrate bile-salts
      sucrose (TCBS) medium for culture of all stool specimens. Vibrio isolates from
      diarrheic patients included V. cholerae-O1 (75), V. cholerae non-O1 (10) and V.
      parahaemolyticus (21). The illnesses were diverse, ranging from mild to severe,
      and in most instances requiring hospitalization, rehydration as well as
      antibiotic treatment. Eighty patients were hospitalized and six died mainly from
      hypovolemic shock and acute renal failure arising from excessive fluid loss. The
      low vibrio-associated mortality observed in this outbreak may have been
      influenced by the proximity and easy transit access to the health care facilities
      offered by the teaching hospital. This contrasts with the high mortality figures
      reported by Health Centers in the rural areas during the same period. Some
      features of vibrio diarrheas were comparable with those of other enteric
      pathogens. Poorly developed water and sewage disposal systems, contact with sea
      water, consumption of fishery products and leftover foods were the main risk
      factors identified.

PMID- 7812245
TI  - Lead in bone from south Moravian autopsies.
AB  - In bone samples of 181 humans decreased at the age of 0-99 years from Brno and
      surroundings, lead content was determined by the method of atomic absorption
      spectrometry. The geometrical mean of the lead content of the whole set is 2.29
      micrograms.g-1 of dry tissue (min 0.26 max. 29.28 micrograms.g-1). With the age
      the lead content in bone gradually increases from the value of the geometric mean
      of 1.35 micrograms.g-1 in the first year of life to almost a double in the age
      decade of 21-30 years. Up to 80 years it roughly remains on a constant level,
      after the age of 80 it rises again up to the mean value of 4.26 micrograms.g-1.
      Differences between the sexes in the whole set as well as in the individual age
      groups are very small and non significant. Statistically significant differences
      in Pb content in bone were found in the relation to the size of the place of
      residence (P < 0.05); however, no association was proved with the character of
      place of residence, occupation, smoking habits or type of the underlying cause of
      death.

PMID- 7812246
TI  - Pneumoconioses in Bulgaria--prevalence, development, prognosis and prevention.
AB  - Prevalence of the basis types of pneumoconioses (silicosis, silicotuberculosis,
      asbestosis) in Bulgaria was studied during a 7-year period (1985-1991).
      Information was taken from reports of the Department for silicosis and other
      pneumoconioses control in the country. As a basis of the investigation serves the
      total number of workers endangered by dust exposure in different risk branches.
      The more rarely encountered pneumoconioses are referred to in absolute numbers.
      Trends in the development and prognosis of the most frequently encountered
      pneumoconiosis in Bulgaria could be followed. Recommendations are given for
      future preventive activity.

PMID- 7812247
TI  - Is the [15N]methacetin liver function test suited to estimate environmental
      effects on the maturity of neonates?
AB  - Clinical and paraclinical data of 91 neonates of the Saxon regions of Leipzig and
      of Torgau/Elbe were reviewed and correlated to the environmental conditions of
      the places of residence of their mothers during pregnancy. One of the parameters
      investigated was the hepatic detoxification capacity of the neonates measured by
      15N elimination rates in the [15N]methacetin urine test. Because of heavy air
      pollution in the places of residence of some of the pregnant women, a distinct
      reflection of environmental influence in the parameters was expected. While some
      of the parameters considered, such as birth weight and bilirubin levels, did not
      correlate with mean exposure data of the residences of the pregnant women, the
      mean rate of the age-dependent maturation of hepatic 15N elimination did. This
      maturation was seen to be significantly decreased in heavily polluted districts
      of the Leipzig region compared to lower polluted places of Leipzig and to the
      lowly polluted region of Torgau/Elbe.

PMID- 7812248
TI  - Prevalence of antibodies to Coxiella burnetii in blood donors in the Czech
      Republic.
AB  - In 1988-1993, a total of 3,732 sera of blood donors from two districts
      (Strakonice and Novy Jicn) of the Czech Republic were tested for antibodies to
      Coxiella burnetii. Using the complement-fixation test at titers of 8 (10) and
      higher, the antibodies were detected in 41 (1.1%). No statistically significant
      difference in seroprevalence between the Strakonice and Novy Jicin districts was
      found (chi 2 = 2.536, P = 0.112, d.f. = 1). Antibodies were ascertained in 36
      donors, 24 of which worked in agriculture. In one donor, antibodies persisted for
      at least 21 months. The highest ascertained titer was 160.

PMID- 7812249
TI  - Albumin in the saliva--a significant indicator of the effect of "outdoor
      schools".
AB  - In 234 children residing permanently in a region with a high level of atmospheric
      pollution indicators of salivary immunity were studied as criteria for assessing
      the efficacy of applied compensatory measures. In the saliva SlgA, IgM, IgG,
      lysozyme, and albumin were determined. A marked reduction of elevated albumin
      levels which are characteristics of irritation or even inflammation in the oral
      cavity or respiratory tract was found in children who in the winter season spent
      some time in an unpolluted rural area. Statistically significant changes in IgM
      levels were demonstrated in these children.

PMID- 7812250
TI  - DNA fingerprint analysis of drug resistant Mycobacterium tuberculosis strains
      isolated in the Czech Republic.
AB  - DNA fingerprints were established in 12 drug resistant and 12 susceptible M.
      tuberculosis strains collected from patients residing in Prague, Czech Republic.
      The Restriction Fragment Length Polymorphism (RFLP) technique was based on the
      detection of the insertion sequence IS6110 in PvuII digested chromosomal DNA. All
      investigated strains possessed at least 5 copies of IS6110 ranging from 5 to 15
      copies in the drug resistant isolates and 5 to 11 copies in susceptible isolates.
      Three multidrug resistant strains displayed identical fingerprints (5 bands), and
      two strains resistant to pyrazinamid had the same banding pattern (12 bands). The
      remaining isolates differed either in number or location of the IS6110 copies.
      Thorough epidemiological analysis did not furnish proof of direct contact among
      these patients.

PMID- 7812251
TI  - Characteristics of virulence signs of enteroinvasive Escherichia coli (EIEC)
      isolated in CSFR and Bulgaria in 1988-1990.
AB  - During 1988-1990 a total of 345 virulent and avirulent strains of enteroinvasive
      E. coli (EIEC) were isolated from human faeces in microbiological laboratories in
      Prague and Sofia. This group of strains belonged to a total of 11 serotypes. The
      most frequently encountered serotypes in both laboratories were: 0124, 0164 and
      028ac. From patients 205 strains were obtained and from healthy subjects 140
      strains of EIEC. In all strains the following signs of virulence were
      investigated: biochemical properties, serotypes, Sereny's test, test on HeLa
      cells, sensitivity to colicine JS and the plasmid profile. The presence of high
      molecular plasmid 140 MDa correlated closely with positive results of the above
      mentioned tests. Plasmid 140 MDa was more frequently present in E. coli strains
      isolated from faeces of patients (in 76.09%) than in strains from healthy
      subjects (in 23%). The strains circulating in the healthy population were in the
      majority avirulent.

PMID- 7812252
TI  - Detection of serum antibodies in tuberculosis patients.
AB  - Sera of 14 bacteriological confirmed pulmonary tuberculosis and 16 non
      tuberculotic or healthy controls were sampled in Ignace Deen University Hospital
      in Conakry, Quinea. Samples were examined for IgG and IgM antibodies by means of
      enzyme-linked immunosorbent assay (ELISA) using sonicated M. bovis BCG and M.
      avium antigens and were tested for antibodies to HIV-1/HIV-2 as well. Median of
      IgG antibody titres to M. bovis BCG antigen was 1:445 and differed significantly
      from that of the control group (1:149). The median of IgM antibody titres was
      1:79.1 and did not differ statistically from that of control group (1:69.3) as
      well as the antibody titres against M. avium antigen in the IgG and IgM classes
      for both analyzed serum groups. Seven of tested TB patients sera were positive
      for antibodies against HIV-1. The median of IgG antibody titres against M. bovis
      BCG antigen was 1:442 not differing significantly from values of remaining TB
      patients as well as the IgM antibody titre (1:109).

PMID- 7812254
TI  - Socio-economic factors and growth of preschool children attending nurseries in
      Prague, Czech Republic.
AB  - Association between socio-economic circumstances and children's growth was
      investigated in a cross-sectional study in preschool children attending nurseries
      in one district in Prague. Data on socio-economic variables and growth were
      available for 352 children. In presented analysis, height-for-age percentiles are
      used as the outcome. Education of mothers was most strongly related to growth in
      unadjusted analysis. Independent contribution of individual factors was then
      assessed by logistic regression. After adjustment for birth length, parental
      height, frequency of illness, housing and car ownership, children of mothers with
      secondary or lower education had about twice the risk of being in lowest tertile
      of height-for-age (odds ratio 1.91, 95% CI 0.98-3.70) compared with children of
      mothers with university education. Paradoxically, children from families without
      a car had lower risk of delayed growth than those from families with a car (odds
      ratio 0.52, 95% CI 0.28-0.95). Our results suggest that social environment and
      behaviour rather than material conditions determine the physical growth of
      preschool children in Prague 10.

PMID- 7812253
TI  - Antitumor activity of bacterial endotoxins and their subunits in in vitro test.
AB  - The tumoricidal effect of endotoxins and their subunits of Shigella dysenteriae
      serovar 1 of both growth forms and certain other representatives of the
      Enterobacteriaceae family was tested against Nemeth-Kellner mouse lymphoma cells
      using an in vitro assay based on the use of sodium chromate solution yielding
      labelled hexavalent 51Cr ions. The most effective in vitro activity was evidenced
      in both growth forms by S. dysenteriae 1 lipopolysaccharide-protein complex
      (LPSP) (76-92%), lipid A and lipoid B isolated from LPS (77-82%) and lipid A and
      lipoid B from LPSP (53-70%). A direct dependence of the level of the Limulus test
      and pyrogenicity on the tumoricidal activity of a preparation was not
      demonstrated. The influence of selected cations (Cu, Fe, Ca, Mg, Zn) bound to
      selected substances on antitumor activity was monitored. The method of probit
      analysis is recommended as it enables estimation, based on a number of
      concentrations, of the regression line of probable effectiveness of a given
      preparation.

PMID- 7812255
TI  - Redefining psychiatry: implications for practice, training, and recruitment.
      Introduction.

PMID- 7812256
TI  - Mind and brain in psychiatric treatment.
AB  - Psychological and biological components of psychiatric illness must be integrated
      to avoid the perils of reductionism in diagnosis and treatment. With the decline
      of dualism, a number of creative thinkers have conceptualized the mind-body
      problem in a manner that values perspectives derived from psychoanalytic thinking
      as well as from the neurosciences. Similarly, modern studies of the etiology and
      pathogenesis of major psychiatric disorders suggest that only through a
      sophisticated synthesis of psychosocial and genetic/biochemical points of view
      can causation be comprehensively understood. In light of this accumulating
      knowledge, the author concludes that treatment must be informed by
      psychotherapeutic approaches as well as by pharmacotherapy.

PMID- 7812257
TI  - Economics redefining the practice of psychiatry.
AB  - Major economic forces are dramatically affecting the practice of psychiatry. In
      the light of these changes, the author suggests how psychiatrists can have an
      expanded role in the emerging outcome-driven world of health care.

PMID- 7812258
TI  - Human resource needs, health care reform, and the practice of
      medicine/psychiatry.
AB  - Health care reform, which is anticipated at the federal level and is ongoing at
      the state level, presents both challenges and opportunities for psychiatrists and
      other mental health practitioners. It is important that all the mental health
      professions examine their training programs in preparation for the changes that
      are likely to occur in the future. The author relates training and practice
      trends to trends in mental health services delivery that are likely to accelerate
      in the context of health care reform.

PMID- 7812259
TI  - Another 'dangerous opportunity': child and adolescent psychiatry faces health
      care reform.
AB  - Child and adolescent psychiatry has evolved into its present form through a
      series of crises over the past 75 years. The current challenge posed by health
      care reform represents the next developmental opportunity for this subspecialty.
      The author presents a brief summary of these crises, an overview of other forces
      affecting practice, and a possible model of adaptive approaches to these
      dilemmas. He concludes that there is every expectation that the field will mature
      further in response to this newest crisis.

PMID- 7812260
TI  - The future of residency training in psychiatry.
AB  - Psychiatric residency training faces an uncertain future related both to ongoing
      changes in the health care delivery system and to the current state of knowledge
      within psychiatry itself. The author discusses issues concerned with financing,
      models of training, clinical settings, generalist versus subspecialist training,
      psychotherapy training, caring for the chronically mentally ill, selection,
      assessment of quality, and enhancement of the quality of training. He concludes
      that, whatever form health care takes, psychiatric educators must maintain a
      commitment to acquiring and communicating new knowledge as the essential basis
      for a high-quality education.

PMID- 7812261
TI  - Redefining psychiatry: implications for educators and medical student education.
AB  - Psychiatric education must be reevaluated and changed in response to increasing
      knowledge in the field, ongoing health care reform, decreased inpatient stays,
      changing reimbursement and other faculty fiscal pressures, the generalist
      physician priority, and fewer students entering the field. The author offers
      recommendations for preclinical patient interviewing, supervision, and follow-up;
      revision of the behavioral sciences course; new lectures in clinical clerkship
      rotations; attention to faculty attitudes toward students; faculty teaching
      competence; the importance of role modeling and mentoring; and the need for
      electives to encourage students to select psychiatry. An improved relationship
      with other physician colleagues is a priority to decrease stigma toward
      psychiatry.

PMID- 7812262
TI  - The impact of the family on careers in psychiatry.
AB  - As more women with young children enter psychiatry, more attention needs to be
      placed on issues that arise because of conflicts between work and family. Some
      issues are unique to women, and some are related to dual-career families as a
      whole. The author outlines these issues and explores how the psychiatric
      profession can alleviate the stress often encountered by the professional family.

PMID- 7812263
TI  - American psychiatry in the 21st century: the discipline, its practice, and its
      work force.
AB  - As the 21st century nears, various forces are affecting American mental health
      care delivery. After reviewing these forces in terms of their impact on
      psychiatry, the author summarizes the nature of psychiatry and psychiatric
      practice as branches of medicine. He then presents a picture of new and
      graduating psychiatric residents, focusing on (1) their changing views of the
      role of biological and psychological work with patients, and (2) their future
      career plans. The author concludes with a challenge to maintain a definition of
      psychiatry that links mind and brain, and from this foundation to demonstrate to
      students, society, and policymakers alike a model of psychiatry that integrates
      biological, psychological, and social perspectives in the treatment of patients.

PMID- 7812264
TI  - The future of psychiatry and implications for recruitment.
AB  - Psychiatry faces challenges involving the recruitment of new psychiatrists. After
      providing a historical perspective on the development of psychiatry as a medical
      specialty, the author highlights current issues affecting recruitment. He
      concludes by emphasizing the unique character of psychiatry as a key factor in
      attracting new psychiatrists.

PMID- 7812265
TI  - Effect of lysophosphatidic acid on motility, polarisation and metabolic burst of
      human neutrophils.

PMID- 7812266
TI  - Effects of recombinant human gamma interferon on intracellular survival of
      Bordetella pertussis in human phagocytic cells.
AB  - Several studies have demonstrated that Bordetella pertussis has the ability to
      enter and survive intracellularly within human polymorphonuclear leukocytes
      (PMNL) and human monocytes/macrophages. The effects of human recombinant gamma
      interferon (IFN-gamma) on the survival of B. pertussis in PMNL and human
      monocytes, and on the oxidative burst activity of PMNL and human monocytes in
      response to B. pertussis were assessed in this study. IFN-gamma partially
      increased intracellular killing of phagocytosed B. pertussis in human monocytes,
      as determined by an orange acridine-crystal violet assay. In contrast, IFN-gamma
      did not enhance intracellular killing of B. pertussis in PMNL. No significant
      increase of superoxide production was noted in human monocytes in response to B.
      pertussis when stimulated with various concentrations of IFN-gamma. The partial
      increase of B. pertussis killing by IFN-gamma within monocytes, together with
      poor production of superoxide may explain how B. pertussis can survive within
      human phagocytic cells, and thus cause a more prolonged course of the disease.

PMID- 7812267
TI  - The sialic acid-containing lipopolysaccharides of Salmonella djakarta and
      Salmonella isaszeg (serogroup O: 48): chemical characterization and reactivity
      with a sialic acid-binding lectin from Cepaea hortensis.
AB  - Lipopolysaccharides (LPS) of Salmonella djakarta and Salmonella isaszeg, as well
      as of a spontaneous R-mutant of S. djakarta were investigated as to their content
      in neuraminic acid (Neu) and its individual linkage. The two Salmonella serovars
      both belong to the O:48 serogroup of Salmonella, but to two different subgroups.
      LPS of both S-forms contained high amounts of Neu, although in different
      quantities, whereas the R-form was completely devoid of it. Methylation analysis
      indicated that Neu is exclusively terminally linked in S. djakarta whereas both
      terminal and 4-linked Neu were recognized in S. isaszeg. Although terminally
      linked, a sialidase from Arthrobacter ureafaciens was unable to split Neu even
      after prolonged incubation from both S-type LPSs. When LPS was first treated by
      mild alkali, however, the total amount of Neu from S. djakarta LPS and about 50%
      from that of LPS of S.isaszeg could be removed. In contrast, alkali-treated LPS,
      but also the non-treated one, proved to be effective inhibitors for a sialic acid
      binding lectin from Cepaea hortensis. The resistance of terminal Neu towards
      sialidase may be due to the presence of an O-acetyl group which would be removed
      during the methylation analysis but would, especially when linked to C-4, not
      interfere with the reactivity of the lectin.

PMID- 7812268
TI  - Interaction of virulent and non-virulent Rhodococcus equi human isolates with
      phagocytes, fibroblast- and epithelial-derived cells.
AB  - Rhodococcus equi is a facultative, intracellular, Gram-positive coccobacillus,
      increasingly reported in pneumonia of AIDS-infected patients. We investigated
      killing resistance properties of human R. equi virulent and avirulent human
      strains. Avirulent beta-lactam-susceptible strains had lower intracellular colony
      forming units after 45 min incubation in murine macrophages J774 and human
      monocyte-macrophage TPH-1 than those of virulent strains. Only virulent beta
      lactam-resistant strains persisted within macrophages for at least 18 min only. A
      beta-lactam-resistant mutant was obtained from a beta-lactam-susceptible strain
      after selection in a penicillin G-containing culture medium. This mutant strain,
      like the natural virulent strains, persisted within macrophages, harboured cell
      associated appendages, produced phage-like particles and induced, after its
      intravenous inoculation, a chronic infection in BALB/c nude mice. Supernatant
      culture of virulent strains transferred partial macrophage-killing resistance
      properties to avirulent strains. The same supernatant was toxic for L-929, HeLa
      and Vero cell cultures. These supernatant effects were heat-inactivated, trypsin
      inactivated and did not seem to be linked to phage-like particle presence. These
      data argue that virulence, beta-lactam-resistance, and macrophage-killing
      resistance are associated in human R. equi isolates. Moreover, only virulent
      strains produced uncharacterized toxic factors.

PMID- 7812269
TI  - Fimbriation, surface hydrophobicity and serum resistance in uropathogenic strains
      of Escherichia coli.
AB  - A total of 80 Escherichia coli strains were examined for expression of P
      fimbriae, mannose-sensitive haemagglutination (MSHA) and mannose-resistant
      haemagglutination (MRHA) of human group A erythrocytes and guinea pig
      erythrocytes, cell surface hydrophobicity and resistance to serum bactericidal
      activity. Isolates were obtained from urine of children and adults, either with
      acute pyelonephritis (n = 15 and n 12) or lower urinary tract infection (UTI) (n
      = 30 and n = 23, respectively). Results obtained showed that, in E. coli strains
      isolated both from children and adults with lower UTI, significant differences
      were not found concerning the incidence of P-fimbriae, cell surface
      hydrophobicity and serum resistance. In pyelonephritogenic E. coli isolated from
      children and adults, the incidence of P-fimbriae and cell surface hydrophobicity
      was associated more frequently with the former (87% vs. 42% and 100% vs. 67%, P <
      0.05), while serum resistance was associated with the latter (47% vs. 67%, P <
      0.05).

PMID- 7812270
TI  - Significance of detection of immune-complexed 8 kDa hydatid-specific antigen for
      immunodiagnosis of hydatidosis.
AB  - Three micro-enzyme-linked immunosorbent assay (micro-ELISA) systems were
      developed and evaluated for detection of specific free circulating antigen and
      circulating immune-complexes (CICs) of 8 kDa antigen in the sera of patients with
      hydatidosis. All (100%) the sera of 30 confirmed positive cases of hydatidosis
      had detectable levels of antigen in the acid-treated sera. However, 23 (77%) and
      26 (87%) sera of 30 confirmed cases had free as well as CICs of 8 kDa antigen in
      the untreated and in the polyethylene glycol (PEG) precipitated sera,
      respectively. None of the sera from other patients with parasitic infections or
      viral hepatitis had any detectable levels of 8 kDa antigen in the untreated, acid
      treated or PEG-precipitated serum samples. The investigations, therefore,
      suggested that the demonstration of circulating antigen employing monospecific
      antibodies to affinity purified 8 kDa antigen in acid-treated sera is more
      efficient as compared to detection of free circulating antigen or CICs in the
      untreated or in the PEG-precipitated sera which could provide a specific
      immunodiagnostic tool for ongoing hydatid infection.

PMID- 7812271
TI  - Diphosphoryl lipid A derived from the lipopolysaccharide (LPS) of Rhodobacter
      sphaeroides ATCC 17023 is a potent competitive LPS inhibitor in murine macrophage
      like J774.1 cells.
AB  - Pentaacyl diphosphoryl lipid A derived from the nontoxic lipopolysaccharide (LPS)
      of Rhodobacter sphaeroides ATCC 17023 (RsDPLA) did not induce tumour necrosis
      factor-alpha nor interleukin-6 release in the murine macrophage-like cell line
      J774.1. However, it effectively inhibited the induction of these two cytokines by
      LPS of Salmonella minnesota Re mutant R595 (ReLPS) in a concentration-dependent
      manner. Maximal inhibition and half-maximal inhibition occurred when the ReLPS to
      RsDPLA mass ratio was 1:30 and 1:1, respectively. A binding study was performed
      in the presence of serum to determine whether RsDPLA is competing with ReLPS for
      LPS binding sites on J774.1 cells. This assay allows the determination of LPS
      binding to J774.1 cells via a mechanism involving CD14, a receptor for complexes
      of LPS with LPS binding protein (LBP), and its possible inhibition. The results
      show that RsDPLA strongly inhibits the binding of 125I-labelled ReLPS to J774.1
      cells. Maximal and one-half maximal inhibition of binding occurred when the ReLPS
      to RsDPLA mass ratios were 1:2.5 and 1:0.5, respectively. It was found that the
      inhibition of binding by RsDPLA was much stronger than that by unlabelled ReLPS.
      These results suggest that RsDPLA is competing with ReLPS for CD14-dependent
      recognition of LPS on J774.1 cells.

PMID- 7812273
TI  - Temperature and frequency effects in tooth enamel electron spin resonance
      dosimetry.
AB  - Electron spin resonance of CO3(3-) molecule ions in human tooth enamel have been
      studied at various temperatures between 4 and 350 K and at various microwave
      powers in the 9 GHz (X) band. Signal saturation during cooling due to slowing
      down of the electron spin relaxation has been established. The 35 GHz (Q) band
      spectra of tooth enamel, irradiated with various gamma-ray doses, are also
      presented. Q band ESR dosimetry offers some advantages over the X-band dosimetry
      due to signal enhancement from the spin level population difference and
      especially due to a better filling factor which is important when only minute
      quantities (a few mg) of enamel are available.

PMID- 7812272
TI  - The effects of growth in human serum on an acapsular group B Streptococcus
      mutant.
AB  - A Group B Streptococcus Type III (GBS) mutant which, when grown in Todd Hewitt
      broth (THB), does not produce any detectable capsule, produced a clearly visible
      polysaccharide capsule when grown in human serum. We isolated cytoplasmic
      membranes from GBS and separated the component membrane proteins by
      polyacrylamide gel electrophoresis. A significant change in membrane composition
      was found during growth in human serum. Several unique proteins were produced on
      serum growth and there was both up- and down-regulation of other proteins. We
      measured the intracellular levels of sialic acid for a variety of GBS serotype
      III isolates. Interestingly, while there was little difference between the
      intracellular sialic levels of most isolates, the sialic acid level of COH31-15
      grown in THB was over 100% higher than that of any other isolate. When grown in
      serum this pool was reduced to a level similar to that in other strains. The
      concentration of bacterial cell sialic acid was directly correlated with the
      sialic acid content of the serum. Exogenous sialic acid content, in concert with
      other serum factors, plays a role in determining the capsular size in GBS.

PMID- 7812274
TI  - Synthesis of the fluorine-18 labeled inhalation anesthetics.
AB  - Fourteen compounds (fluoroalkanes and fluoroethers), including the two most
      utilized inhalation anesthetics Isoflurane (CF3CHClOCF2H) and Halothane
      (CF3CHBrCl), have been labeled with fluorine-18 via a facile 18F-for-19F exchange
      reaction. The compounds include ten inhalation anesthetics which span a ten-fold
      range in potency and four structurally related non-anesthetics. All the compounds
      possess a trifluoromethyl group (CF3) adjoining a carbon atom with an acidic
      alpha-hydrogen and at least one halogen or a strong electron withdrawing group
      (X), [CF3CHXR]. We postulate the isotopic fluoride exchange reaction proceeds
      through a carbanion transition state resulting from alpha-proton transfer to
      base. The carbanion stability is attributed to the inductive effect of the CF3
      group and the electron withdrawing capability of X. Compounds labeled in dimethyl
      sulfoxide (DMSO) at 125 degrees C in 15 min include Isoflurane-CF3CHClOCF2H (1)
      (97% [18F]fluorine incorporation, 99% radiochemical purity, respectively),
      Sevoflurane-CF3CHCF3OCFH2 (2) [98%, 99%], CF3CHBrOCF2H (3) [85%, 80%], Desflurane
      CF3CHFOCF2H (4) [50%, 99%], Fluroxene-CF3CH2OCH = CH2 (5) [25%, 99%], Fluothyl
      CF3CH2OCH2CF3 (6) [60%, 10% at a temperature of 175 degrees C], Halothane
      CF3CHBrCl (7) [98%, 95%], CF3CH2I (8) [99%, 98%], CF3CH2Br (9) [18%, 98%],
      CF3CHCl2 (10) [95%, 98%], CF3CH2Cl (11) [90%, 20%], CF3CHClCF3 (12) [95%, 99%],
      (CF3)3CH (13) [99%, 99%] and HF-134a-CF3CFH2 (14) (15%, 93% at a temperature of
      175 degrees C).

PMID- 7812275
TI  - The benefits and pitfalls of health services research funded by proprietary
      firms.

PMID- 7812276
TI  - Individual quality of life in the healthy elderly.
AB  - Quality of life research with the elderly has usually focused on the impact of
      decline in function, and used a pre-determined model of quality of life in old
      age. The Schedule for the Evaluation of Individual Quality of Life (SEIQoL)
      allows individuals to nominate, weigh and assess those domains of greatest
      relevance to their quality of life. The SEIQoL was administered to 56 healthy
      elderly community residents at baseline and 12 months later. Quality of life
      levels were significantly higher at baseline (t = -2.04; p = 0.04) than that of a
      previously studied sample of healthy adults below 65 years of age, and did not
      change significantly over the study period. The domains nominated by both samples
      as relevant to their quality of life differed notably. Health status was not
      correlated with the perceived importance of health at baseline, and showed only a
      low correlation (r = 0.27) at 12 months. The weight placed on health did not
      increase over the study period despite a significant decline in health status.
      The value of allowing the individual to define personal quality of life values in
      a research context is explored.

PMID- 7812278
TI  - The time trade-off technique: how do the valuations of breast cancer patients
      compare to those of other groups?
AB  - The time trade-off method was incorporated into a study of valuation of health
      states following treatment for breast cancer. A major aim of the work was to
      determine whether different groups give different valuations. The time trade-off
      technique was simple and quick to administer, acceptable to subjects, and
      produced different values in different groups. Age and sex of valuers had some
      influence: the most striking differences were found between women who had
      experienced breast cancer and those who had not. The time trade-off method has
      considerable potential in health state valuation. The choice of valuers needs to
      be further explored.

PMID- 7812277
TI  - Domains, constructs and the development of the breathing problems questionnaire.
AB  - Health-related quality of life (QoL) questionnaires are commonly developed as
      content valid instruments with conventionally defined domain subscales. We
      contrasted content valid domain subscales with construct valid construct
      subscales and developed a 13-domain QoL questionnaire, the Breathing Problems
      Questionnaire (BPQ), for patients with chronic bronchitis. In a series of
      studies, we examined the constructs relevant to COPD patients' experience of
      health. First, we provided psychometric evidence that items in the BPQ form two
      distinct groups: functional problems and negative evaluations. Second, we showed
      that problems were significantly more correlated with morbidity whereas negative
      evaluations were significantly more correlated with neuroticism. Third, we showed
      that negative evaluations correlated with neuroticism whereas positive
      evaluations (measured by the Satisfaction with Illness Scale) correlated with
      extraversion. Patients are more likely to make positive evaluations of their
      illness when they recognize that they are seriously ill. Most of the BPQ domains
      are subcategories of the construct of problems: both domains and construct
      classifications provide useful information.

PMID- 7812279
TI  - A pilot study of patient quality of life during radiation therapy treatment.
AB  - The purpose of this research was to develop a quality of life (QOL) tool that
      would help to reveal any physical, mental or emotional changes patients may
      experience while receiving radiation therapy. Research focusing on quality of
      life during radiation therapy is in its infancy. Although many tools to measure
      QOL have been developed, until very recently few had been geared specifically
      toward those receiving radiation therapy. In addition to a radiation-specific
      instrument, the goal was to develop a multidimensional measure that would be
      short in length and could be completed by the patient in 15 min or less. This new
      Quality of Life Radiation Therapy Instrument (QOL-RTI) is a visual analogue scale
      with 24 questions and is not site specific. Twenty-one patients with various
      diagnoses and treatment sites completed the questionnaire at baseline and then
      weekly during the course of radiation therapy. The internal consistency of the
      instrument (Cronbach's alpha) was 0.87. At baseline each patient also was asked
      to complete the Ferran's and Powers QLI Cancer Version 6 (QLIC); the correlation
      between the QLIC and the QOL-RTI was 0.47. These results are based on a small
      number of patients, but initial efforts in creating an instrument that is quick
      and easy for patients to complete have been encouraging. An additional 70-80
      patients are now being entered into a study using the QOL-RTI to further evaluate
      reliability and validity.

PMID- 7812280
TI  - Intellectual property considerations in the development and use of HRQL measures
      for clinical trial research.
AB  - As a result of the expanded use of health-related quality of life (HRQL) measures
      in clinical trial research, a variety of legal and ethical issues have surfaced.
      These issues can be put in the form of the following questions: (1) Under what
      circumstances should access to HRQL measures be restricted? (2) Under what
      circumstances is it appropriate for the developers of HRQL measures to assert
      their intellectual property rights to the instruments? (3) Under what
      circumstances is personal profit from the sale and use of HRQL measures legally
      and socially appropriate? Access to HRQL research is to be encouraged since this
      is necessary for this field to progress. However, the need for protection against
      misuse of ongoing work is real and may justify the assertion of intellectual
      property rights. HRQL measures developed entirely with public monies should
      remain in the public domain or be managed for the public good. Instruments
      developed with private funds or with a mix of public and private funds should be
      treated in a manner that reflects a fair balance between the rights of the
      private developer and those of the scientific community and the public. HRQL
      questionnaires are regularly being refined; such work is costly. Investigators
      continuing research directly related to instrument refinement might reasonably
      ask for compensation from those who wish to use their work.

PMID- 7812282
TI  - [Has the gene of osteoporosis been disclosed?].

PMID- 7812283
TI  - [Trabecular bone architecture: characterization by a method of fractal analysis].

PMID- 7812281
TI  - Research on health-related quality of life: dissemination into practical
      applications.
AB  - Strategies and processes for the effective dissemination and diffusion of
      research findings on health-related quality of life (HQL) into practical
      applications were explored at a workshop held in Montreal in April, 1994. A
      conceptual model for dissemination and diffusion of evidence about HQL was used
      to identify five different target groups: HQL assessors, policy makers, planners
      of clinical trials, developers of clinical practice guidelines, and those at the
      level of patient-practitioner clinical decision making. A framework designed to
      facilitate the translation of fundamental research knowledge into effective
      action was then used as a starting point for discussions about priorities for
      research on HQL. The most important problem identified at the workshop was how
      best to strike an appropriate balance between priorities deemed to be important
      to those directly involved in HQL research, and priorities deemed to be important
      to potential users of the results of HQL research?

PMID- 7812285
TI  - [Serum phospholipase A2 activity in osteoarthritis].
AB  - Serum phospholipase A2 activity in 67 osteoarthritis patients and 17 controls was
      determined using a radiolabeled specific substrate. Serum phospholipase A2
      activity was significantly higher in osteoarthritis patients (115 +/- 73.6
      dpm/h/ml) than in controls (45 +/- 25 dpm/h/ml) (p = 0.002). In 41 osteoarthritis
      patients, serum phospholipase A2 activity was unrelated to age, time since onset
      of osteoarthritis symptoms, duration of morning stiffness, Lequesne's index,
      roentgenographic stage of osteoarthritis, number of joints with osteoarthritis,
      erythrocyte sedimentation rate, or serum C-reactive protein levels. In 12
      osteoarthritis patients who were evaluated twice at a mean interval of 46 days,
      changes in serum phospholipase A2 activity were unrelated to changes in
      Lequesne's index. Blind evaluation of long-term joint space loss was performed in
      14 patients; serum phospholipase A2 activity increased only in those patients
      with progressive joint space loss, but the difference was not statistically
      significant as compared with the controls. These data suggest that serum
      phospholipase A2 activity is not useful in practice as a marker for
      osteoarthritis.

PMID- 7812284
TI  - [Demonstration of subclinical pulmonary alveolitis in spondylarthropathies].
AB  - Restrictive ventilatory dysfunction, lowered diffusing capacity, and apical
      fibrosis have been reported in ankylosing spondylitis. To investigate the
      pathogenesis of these abnormalities, we studied distal airspace cytology by
      performing bronchoalveolar lavage in 34 spondyloarthropathy patients (ankylosing
      spondylitis, n = 16; reactive arthritis, n = 4; axial psoriatic arthritis, n = 2;
      and undifferentiated spondyloarthropathy with HLA B27-positivity in every case
      but one, n = 12). Mean age was 32.4 +/- 13.7 years. None of the study patients
      had apical fibrosis, lower respiratory tract infection, or exposure to airborne
      pollutants other than tobacco smoke. The control group was composed of nine
      subjects who had no lung or inflammatory diseases and were not using medications.
      Significantly higher proportions of lymphocytes were found in bronchoalveolar
      lavage specimens from patients, as compared with controls. This difference was
      not influenced by smoking or medication use (non steroidal antiinflammatory
      drugs, sulfasalazopyridine). Alveolar lymphocytosis was not correlated with
      laboratory tests for disease activity (erythrocyte sedimentation rate, serum IgA
      levels) or with the presence of restrictive ventilatory dysfunction. Increases in
      the proportion of lymphocytes were of similar magnitude in patients with
      ankylosing spondylitis and in those with other spondyloarthropathies. Absolute
      total cell counts and relative neutrophil counts were similar in patients and
      controls. However, among the patients with spondyloarthropathies, those with a
      disease duration of more than five years had a significantly higher proportion of
      neutrophils than those with a disease duration of less than five years. These
      findings demonstrate that spondyloarthropathy patients have subclinical
      lymphocyte alveolitis. Although of unclear significance, this alveolitis may be
      related to the development of apical fibrosis in some patients with ankylosing
      spondylitis.

PMID- 7812287
TI  - [Respective evaluations of mechanical and vascular factors in the pathogenesis of
      neuroacropathy].
AB  - The purpose of this study was to determine the respective contributions of
      microcirculatory dysfunction and mechanical stresses to the pathogenesis of
      neurogenic trophic lesions. All patients with polyneuropathy complicated by
      cutaneous or osteoarticular trophic lesions (perforating forefoot ulcers,
      neurogenic osteoarthropathy) were eligible for the study. Patients with vascular,
      articular or neurological disorders other than the polyneuropathy were excluded.
      Digital photoplethysmography was used to evaluate microcirculatory reactivity.
      Electronic podometry was performed for static and dynamic foot pressure studies.
      A technetium-99m bone scan was done to look for evidence of neurogenic
      osteoarthropathy. The study included 35 patients (16 with alcohol abuse, 7 with
      diabetes mellitus, 10 with both disorders, one with Charcot-Marie-Tooth disease,
      and one with neuropathy of unknown etiology). Cutaneous or osteoarticular trophic
      lesions were correlated with the presence of static podoscopic abnormalities
      (dynamic abnormalities apparently had no influence per se). Digital vasoplegia
      was found in 8 of 35 patients (23%) and was closely correlated (p < 0.0001) with
      severity of the osteoarthropathy. These data suggest that mechanical factors play
      the central role in the production of neurogenic trophic lesions and that
      microcirculatory dysfunction may be a marker for severe neurogenic
      osteoarthropathy rather than a causative factor.

PMID- 7812286
TI  - [Study of femoro-tibial cartilage diseases with MRI].
AB  - Magnetic resonance imaging provides excellent tissue contrast resolution and can
      therefore be used to visualize joint cartilage. The goal of this study was to
      evaluate the value of magnetic resonance imaging for the diagnosis of
      femorotibial cartilage lesions. Spin-echo magnetic resonance imaging was
      performed in 37 patients. As compared with arthroscopy, the accuracy,
      sensitivity, and specificity of magnetic resonance imaging were 72.5%, 47%, and
      95.5%, respectively. Only advanced cartilage lesions with exposure of subchondral
      bone were clearly seen on magnetic resonance sections. Limiting factors included
      insufficient spatial resolution and the chemical shift phenomenon. Spin-echo
      sequences used in everyday practice are not appropriate for detecting small
      cartilage lesions. Controlled studies are needed to determine whether gradient
      echo sequences are more satisfactory.

PMID- 7812288
TI  - [Side-effects during treatment of rheumatoid arthritis with methotrexate].
AB  - Methotrexate is the drug with the highest long-term continuation rate in
      rheumatoid arthritis patients. However, toxicity is the main reason for
      methotrexate withdrawal. Most adverse effects are mild abnormalities, such as
      digestive symptoms, stomatitis, elevations in transaminase levels, and moderate
      decreases in peripheral blood cell counts. Potentially life-threatening effects
      include hypersensitivity pneumonitis and pancytopenia. Cirrhosis is less common
      than in patients with psoriasis. Opportunistic infections and Epstein-Barr virus
      related lymphomas have been reported. Neurological disorders, cutaneous reactions
      and renal lesions have been ascribed to low-dose methotrexate. Prior renal
      dysfunction and concomitant administration of a number of drugs, including
      cotrimoxazole, have been shown to increase methotrexate toxicity. However,
      susceptibility to the toxic effects of methotrexate varies widely across
      individuals. The effectiveness of folate supplementation in preventing
      methotrexate toxicity remains controversial.

PMID- 7812289
TI  - [Does septic arthritis occur in human immunodeficiency virus infection?].
AB  - No prospective, longitudinal, cohort studies comparing septic arthritis in HIV
      positive and HIV-negative individuals belonging to the various risk factor groups
      for HIV-infection are available. However, a review of the literature provided
      information on the main features of pyarthrosis in HIV-infected patients. The
      clinical and microbiological characteristics, as well as the outcome of this rare
      complication, vary with the risk factor group and with the severity of the immune
      deficiency. Pyogenic bacteria are the most common causative agents and should be
      looked for routinely since they usually respond well to antimicrobial therapy.

PMID- 7812290
TI  - [Inferior glenohumeral subluxation: an indirect sign of sepsis of the shoulder].
AB  - Drooping shoulder is a roentgenographic abnormality consisting in a discontinuity
      in the scapulo-humeral arch due to inferior subdislocation of the humeral head.
      Drooping shoulder is commonly seen in patients with injuries to the shoulder or
      neurological loss. Two cases of drooping shoulder due to staphylococcal arthritis
      (after local corticosteroid injections) are reported herein. The mechanism of the
      downward humeral displacement in septic arthritis is discussed. The other causes
      of drooping shoulder are reviewed. Precautions needed to avoid increasing the
      displacement during rehabilitation therapy are outlined.

PMID- 7812291
TI  - [Paget's disease of bone associated with autoimmune thyroiditis and joint
      chondrocalcinosis].
AB  - A case of scapular Paget's disease of bone with concurrent autoimmune thyroiditis
      and articular chondrocalcinosis is reported. Although infrequent, this
      combination suggests the involvement of common pathogenic mechanisms: thyroiditis
      and Paget's disease may stem from the same viral infection and/or autoimmune
      disorder, whereas chondrocalcinosis may be the consequence of thyroiditis-related
      hypothyroidism. In contrast, the association of Paget's disease and
      chondrocalcinosis may be fortuitous, since both disorders are common.

PMID- 7812292
TI  - [Lymphoma during treatment of rheumatoid arthritis with low-dose methotrexate: a
      new case].

PMID- 7812293
TI  - [Pathogenic role of epidural fat in lumbar stenosis? Apropos of a surgically
      treated case].

PMID- 7812294
TI  - [Benign schwannoma of the calf. Apropos of a case].

PMID- 7812295
TI  - [Neuroleptic malignant syndrome induced by a single injection of tiapride].

PMID- 7812296
TI  - [Synovial effusion of the ankle as first manifestation of fibular stress
      fracture].

PMID- 7812297
TI  - Abstracts from the First Congress of the Hungarian Neuroscience Society. Pecs,
      January 27-29, 1994.

PMID- 7812299
TI  - Pressure ulcer treatment. Agency for Health Care Policy and Research.
AB  - This Quick Reference Guide for Clinicians contains highlights from the Clinical
      Practice Guideline version of Treatment of Pressure Ulcers, which was developed
      by a private-sector panel of health care providers and a consumer. Selected
      aspects of pressure ulcer assessment and treatment are presented. Topics covered
      include assessment of the patient and pressure ulcer(s), tissue load management,
      ulcer care, management of bacterial colonization and infection, operative repair
      of the pressure ulcer, and education and quality improvement. Algorithms are
      included to show the sequence of events related to the overall care of the
      individual with a pressure ulcer, nutritional assessment and support, management
      of tissue loads, ulcer care, and management of bacterial colonization and
      infection. Tables and forms are included as aids for selecting irrigation
      devices, cleansing solutions, support surfaces, and assessing the pressure ulcer
      and the patient's nutritional status.

PMID- 7812298
TI  - Patch-clamp study of membrane properties and GABA-activated currents of rat
      magnocellular supraoptic neurons in thin slice preparation.
AB  - The magnocellular neurons of the rat supraoptic nucleus were investigated by
      using (a) the patch-clamp technique on thin brain slice preparations to
      demonstrate voltage- and GABA-activated ionic currents, and (b)
      immunohistochemistry to demonstrate the expression of the beta 2 and beta 3
      subunits of the GABAA-receptor on their membrane surface and the contents of the
      neuropeptides vasopressin and oxytocin. During electrophysiological recording in
      the whole-cell mode neurons were stained with Lucifer Yellow and camera lucida
      drawings were made. Two types of neurons could be distinguished by their
      different K(+)-currents, an inactivating and a noninactivating type. All neurons
      had a fast Na+ inward current. GABAA-activated currents were characterized by
      investigation of their ionic conductance and by blocking experiments with the
      GABAA-antagonist bicuculline.

PMID- 7812300
TI  - [Imaging diagnosis of non-lymph node metastasis of bladder carcinoma].
AB  - Assessment of presence of metastatic disease (m.d.) in bladder cancer (b.c.) can
      represent a main problem as influencing the appropriate therapeutic policy
      (mostly the indication to radical surgery). Evaluation of the real cost
      effectiveness ratio of radiographic and radionuclide diagnostic work-up induced
      us to retrospectively review historical data about our b.c. patients (pts). From
      March 1988 to June 1991, 76 not consecutive pts with histologically proven
      bladder cancer were included in this study. 5 Pts were staged as T1, 25 as T2, 18
      as T3a, 23 as T3b, 5 as T4. 2 Pts were graded as G1, 27 as G2, 44 as G3, 3 as Gx.
      Age varied from 39 to 89 years (average: 62.3). 79 Pts underwent the "basic work
      up" (including chest plain film, bone and liver scans) and at least one follow-up
      control. 266 chest plain films, 22 chest x-ray tomograms, 2 chest CT scans, 27
      bone x-ray tomograms, 231 bone scans, 240 liver scans, 17 liver ultrasonographies
      were totally realized. All pts underwent at least an abdomen-pelvic CT, but
      related results are not considered in the study. Fine needle aspiration cytologic
      biopsies were realized in selected cases; also these results are not selectively
      reported here. Together with cytologic positive results, only progression of m.d.
      was considered as its definite presence. Conventional x-ray examination (plain
      film integrated by x-ray tomograms of "suspicious" findings) resulted
      sufficiently complete and accurate to reveal chest m.d. Concerning skeletal
      diagnostic survey, only 6 pts (26%) out of 23 pts with "positive" bone scans
      really resulted affected by m.d.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7812301
TI  - [Proposal for using mechanical staplers with Polysorb in creation of orthotopic
      neobladder].
AB  - After radical cysto-prostatectomy the bladder substitute is made from an ileal
      segment, opened along its antimesenteric border and folded; the results are in
      general good. The success of this procedure demands attention to detail,
      hemostasis and gentle handling of tissue so this surgery depends an unusual
      degree of commitment to meticulous technique. The very low rate complications,
      obtained with mechanical sutures in gastrointestinal surgery, incited the Authors
      using the staplers GIA and TA Polysorb for detubularized ileal segment. They are
      very manageable, easy to use and the follow-up shows the absence of urinary
      stone; so the team approach is less tedious and strenuous. The Authors present
      their results of 11 neobladder-staplers made with 35 cm of detubularized ileal
      segment without folding.

PMID- 7812302
TI  - [Neoadjuvant chemotherapy in advanced-stage bladder carcinoma. A randomized
      prospective study comparing MVAC and MVEEC].
AB  - The Authors report the results with combination of cisplatin, methotrexate,
      vinblastine with adriamycin or epidoxorubicin (MVAC v MVEEC), in the neoadjuvant
      treatment of muscle-infiltrating bladder cancer (T2-4NO-1MO), before cystectomy.
      MVAC has been used in 29 patients and MVEEC in 25, who met eligibility criteria.
      Results from this prospective randomised trial show that MVAC and MVEEC can
      produce clinical and pathologic down-staging in 40-50% of cases: cCR+cPR are
      15/28 (54%), pCR+pPR are 11/25 (44%). The survival duration of "pathologic"
      responders has been significantly longer than that of no responders (median no
      achieved at 200 weeks v 124 weeks for "pathologic" no responders). We conclude
      that neoadjuvant chemotherapy with MVAC or MVEEC select the more responsive
      patients, who have a longer survival.

PMID- 7812303
TI  - Unsuspected neoplastic disease of ureteric stump in patients undergoing
      cystectomy for bladder cancer.
AB  - Unsuspected neoplastic disease of the ureteric stump was discovered in 4 of 47
      patients (8.5%) undergoing cystectomy for bladder cancer between 1988 and 1990.
      Carcinoma in situ was found in one case; invasive cancer was present in 3 cases.
      Ureteric malignancy was found only in patients with undifferentiated bladder
      tumor or with a widespread involving of the upper tract of ureter and pelvis. No
      carcinoma in situ or tumor was discovered in the distal ureter in patients with
      localized transitional cell carcinoma of the bladder. This research emphasizes
      the low risk to constructing uretero-intestinal anastomosis with unsuspected
      tumor in the distal margin of ureter in patients with a transitional cell
      carcinoma of the bladder.

PMID- 7812304
TI  - [Instrumental chemolysis of cystine calculi].
AB  - ESWL and PCN have modified the urinary stones therapy. Nevertheless these
      therapeutic procedures are not much effective in cystine stone because of its
      protein structure and frequent recurrences; these procedures need to be combined
      to achieve the best results. In cystine stones the lithochemolysis, performed
      following recent technique has shown excellent results, without complications and
      easy to apply.

PMID- 7812305
TI  - [Prevention of renal calculosis: efficacy of Fiuggi water cure. Research Group on
      Renal Calculosis].
AB  - High fluid intake is the only nutritional modification that is universally agreed
      to be useful in all forms of nephrolithiasis. Particularly the use of
      oligomineral waters seems to be important as they can obtain a high urine volume
      with a low electrolytes concentration. The aim of this study was to evaluate the
      effects of an oligomineral water (Fiuggi) on some urinary parameters on different
      regimens of therapy. Out of 200 patients (118 M., 82 F., mean age 53 +/- 13
      years), arrived to our outpatient Kidney Stone Center in Fiuggi, a random of 100
      was submitted to water cure with more than 1500 ml/die of Fiuggi water for a
      period of 7 and 14 days, the other 100 patients to less than 1500 ml/die for the
      same periods. All the patients had a history of stone disease. Urinary values of
      calcium, phosphate, uric acid, magnesium, potassium, pH and density were measured
      in all groups of patients before and after water cure. Data were analyzed in
      unvaried method and were presented as mean +/- S.D. To evaluate the statistical
      differences between the values before and after therapy, the paired t test was
      used. Moreover, the percent changes of the considered parameters in relation to
      their basal values was considered. The 50-70% of all patients showed a reduction
      of the considered urinary parameters, with a statistical significance in patients
      who drunk more than 1500 ml of water. Urinary pH and Mg+/Ca++ ratio increased
      significantly in both groups of patients. The sex and the length of therapy
      didn't show any significant power on these results.

PMID- 7812306
TI  - [Monitoring of low urinary tract infections in patients hospitalized with
      neurological diseases].
AB  - Bacteriological and systematic investigation has been carried on 135 confined to
      bed patients at the Neurological Department of the Policlinico of the University
      of Catania from January 1993 to June 1993, in order to estimate the frequency of
      the I.V.U. and the probable correlations with the basic nerve disease. Infections
      have been found with greater frequency between women and patients with catheter.
      The microorganisms most frequently isolated were: E. coli (36%) and Streptococcus
      faecalis (36%). Patients with positive urine culture have been treated in
      accordance with the indications of the bacterial identification. Particularly,
      surveys carried out in a group of patients suffering from cerebral stroke (81
      cases), showed a frequent association between the I.V.U. and the beforesaid
      pathology. Similar results have been obtained in the two groups of patients
      submitted to 2 and to 3 drawings of urine respectively, practised at a distance
      of 5 of 5 days the one form the other.

PMID- 7812307
TI  - [Percutaneous treatment of postoperative stenosis of ureteropelvic junction. Use
      of the Korth stent].
AB  - Endopyelotomy is, in our opinion, the most proper therapeutic strategy for the
      treatment of UPF post-surgery stenosis, as a traditional re-operation is often
      difficult to be carried out and not exempt from possible stenotic relapse. We
      report 2 cases of secondary stenosis and inferior caliceal stones associated. As
      a first step we subjected the patients to a percutaneous lithotomy of the calculi
      and we kept a trans-calyceal nephrostomy in situ for about 5 days. Among the
      different EPT techniques, we chose the "transurethral traction" Rippa-Franch set,
      as the dynamic combined transurethral traction of the cold-knife allows a smooth
      dissection of the strongest cicatrix pad, too. The stenting of the dissected UPF
      has been carried out for few days by means of a Korth's temporaneous nephrostomy
      and subsequently, at light-coloured urine, by using the definitive Korth
      endostent by subcutaneous anchorage. This internal stenting system seems to be
      the most suitable one, as the patient can stand it quite well for long periods of
      time (3-6 months) too and it is not burden with V-U refluxes that could
      jeopardize the good result of the operation. The easy performance and good
      results achieved by this way, persuade us to suggest this two combined techniques
      as an effective endourological solution for UPF post-surgery stenosis.

PMID- 7812309
TI  - [Stenosis of ureteroneocystostomy: endoscopic resection. A clinical case].
AB  - The Authors report a case of ureterocystoneostomy sec. Paquin stenosis treated
      with endoscopic resection of ureteral coupling and of vesical wall with
      satisfactory results.

PMID- 7812308
TI  - [Lymphoma and renal failure].
AB  - The Authors examine the main causes of renal failure in lymphoma (infiltration of
      kidneys, glomerulonephritis, paraproteinemic nephropathy), the difficulties for a
      correct diagnosis with ultrasonography, urography and CT scan, the importance of
      renal biopsy. The histologic examination should be promptly performed in patients
      with sudden renal failure of unknown aetiology and clinical suspicion of
      malignancy, because renal function can improve dramatically with aggressive
      chemotherapeutic treatment of lymphoma.

PMID- 7812310
TI  - Investigation of chloroquine intake in Biombo region, Guinea Bissau.
AB  - The use of chloroquine (CQ), during the dry season was determined for 236
      patients from 5 villages in Biombo, Republic of Guinea Bissau, West Africa. The
      antimalarial drug was measured in whole blood (dried samples) using High
      Performance Liquid Chromatography (HPLC) and in urine samples by Enzyme Linked
      Immunosorbent Assay (ELISA). The results showed that CQ consumption is low.

PMID- 7812311
TI  - Studies on filariasis in Bauchi State, Nigeria. II. The prevalence of human
      filariasis in Darazo Local Government area.
AB  - In an eleven months study of eleven communities of Darazo Local Government Area
      of Bauchi state, northern Nigeria, 293 (21.7) of 1,349 persons examined harboured
      various filarial parasites. Of the sampled population, 18%, 1.9%, 1.6%, 0.5% and
      0.2% had microfilariae of Onchocerca volvulus, Wuchereria bancrofti, Mansonella
      perstans, M. streptocerca and Loa loa respectively. Of the 637 females examined,
      90 (14.1%) were infected, while 203 (23.5%) of 712 males sampled had filarial
      infections. The high rate in males was significant (P < 0.001). O. volvulus mf
      rate increased gradually from the first decade to the seventh decade of life but
      declined thereafter. Prevalence of bancroftian filariasis was consistently lower
      in females of reproductive age, while the distribution of various filarial
      parasites varied significantly among age groups and communities (P < 0.05).
      Fishermen (42.9%), farmers (42.4%) and cattle rearers (40.9%) were the most
      affected occupational categories. Control strategies are highlighted.

PMID- 7812312
TI  - The effect of NeemAzal on Aedes aegypti (Diptera: Culicidae).
AB  - The effect of NeemAzal (TRIFOLIO-M GmbH, Lahnau), a neem seed kernel extract, on
      larvae of Aedes aegypti was tested. Second, third and fourth instar larvae were
      reared in water containing different concentrations of NeemAzal. Mortality rates
      and the stage in which mortality occurred were recorded. The surviving larvae
      were left in the treated water until adult emergence and the number of eggs laid
      by the emerged females was recorded in order to evaluate possible fecundity
      reducing effect of sublethal doses of NeemAzal. Continuous exposure to treated
      water induced molting-inhibition and mortality in all larval instars tested.
      Sensitivity towards NeemAzal decreased with increasing age of the larvae. For
      female Ae. aegypti a tendency was observed to lay fewer eggs with increasing
      NeemAzahl concentration to which they had been exposed during larval development.

PMID- 7812313
TI  - Human bilharzial ureters: IV. Ultrastructural interaction between multinucleate
      giant cells and the parasite eggs.
AB  - The ultrastructural interaction between multinucleate giant cells (MGCs) and the
      Schistosoma haematobium eggs is described at the transmission electron microscopy
      (TEM) level, in granulomas of the lower ureteral segments of Saudi patients. The
      MGCs were found only within the parasite empty egg-shells which were embedded in
      the ureter submucosa and muscularis. For the first time, two morphologically
      different types of MGCs were recognized: the moderate to electron-dense type I
      contained two types of 8-12 nuclei and cytoplasm poor in cell organelles which
      appeared non-functional. Type 1 MGCs were considered to be "old" and non-active
      cells. The electron-lucent to moderately dense type II MGCs contained 3-4 nuclei
      of one type, and cytoplasm rich in cell organelles. According to the performance
      of their organelles, type II MGCs were considered to be "young" and highly active
      cells. The human type II MGCs did not form the cytoplasmic membranous labyrinths
      previously described for the free moving MGCs obtained from experimental mice,
      and were suggested to be involved in the cell motility. As in murine MGCs, type
      II cells were incorporated in exocytic and endocytic activities aimed the
      degradation of the inner soft layer of the egg-shell. This study shows that
      individual macrophages were responsible for eliminating the outer and possibly
      the middle hard layers of the egg-shell.

PMID- 7812314
TI  - Application and evaluation of QBC malaria diagnosis in a holoendemic area.
AB  - Quantitative Buffy Coat Analysis was used in practical diagnosis situations. In
      the first place, sensitivity and specificity was measured in an active search
      survey (720 schoolchildren under 10 years of age, in nine field trips) under
      unfavourable laboratory conditions (onsite school diagnosis being conducted with
      electricity supplied by a diesel-powered generator). In this group, the QBC-based
      study revealed sensitivity and specificity ratings of 99.6% and 81.7%
      respectively. QBC proved 5.5% more sensitive than the thick-film method, but
      specificity was greater with the latter. QBC returned good results when used in
      adverse situations, viz., in the absence of air conditioning and with a diesel
      generator as the only power supply. QBC was used in a passive search survey
      (hospital group, 618 children) under good laboratory conditions (air
      conditioning) with patients enrolled in a trial to measure resistance to
      antimalarial drugs. In this survey we targeted at assessing the efficacy of
      chloroquine treatment at dose of 25 mg/kg/3 days. QBC proved more sensitive than
      the thick-film method, detecting - on day 14 of the in vivo test - low
      parasitaemias that had gone undetected by thick film. Lastly, this study reports
      on the conversion of QBC readings (parasitaemia per field) into thick-field terms
      (number of parasites per microliter of blood), with the aim of measuring the
      degree of recurring parasitaemia.

PMID- 7812315
TI  - Partial characterization of larval antigens of Strongyloides papillosus by
      western blot analysis.
AB  - Western blotting was used to analyse the antigens in extracts of adult and
      infective larvae (SIL) of Strongyloides papillosus with serum of infected
      rabbits. Several proteins in both the extracts reacted with immunoglobulin G in
      the serum. A protein of about 16 kDa in the extract of SIL showed an especially
      strong reaction. No cross-reaction was observed among proteins in the extracts of
      adult worms of such cattle helminths as Fasciola gigantica, Homalogaster
      paloniae, Trichuris discolor and Setaria digitata to S. papillosus-infected
      rabbit serum. The cuticle of the worms and substances in the worm tracks showed
      positive reaction with the immunoperoxidase test on SIL with the serum.

PMID- 7812316
TI  - Colonisation and degradation of dung pats after subcutaneous treatment of cattle
      with ivermectin or levamisole.
AB  - The fauna and degradation of dung pats from cattle treated with ivermectin or
      levamisole were examined in a field study conducted in southern Germany. Four
      groups of seven cattle each grazed on four paddocks. The cattle were treated
      subcutaneously with ivermectin (0.2 mg/kg) or levamisole (5 mg/kg) 3, 8 and 13
      weeks after turnout. A total of 300 pats voided naturally before the first and
      third treatment and 3, 7, 14 and 28 days after treatment were evaluated. Half of
      them were used as sampling pats, in which adult and immature Coleoptera, larvae
      of Diptera and soil and dung nematodes were counted. Earthworms were weighed in
      samples taken on 8 occasions within 63 days after pat deposition. Dung
      degradation was investigated using 150 observation pats by measuring surface
      area, weight and organic matter content on six occasions within 63 days from
      deposition. A photographic record was also maintained. There was no difference
      between treatment groups as to the range of Coleoptera, nematodes and earthworms
      collected from the pats. No quantitative differences between groups were seen
      regarding the total number of adult and immature dung beetles, soil nematodes and
      earthworms isolated within 63 days after deposition. Populations of Diptera
      larvae in pats voided up to 28 days after treatment were reduced for the
      ivermectin treated group relative to the levamisole group. There were reductions
      in numbers of dung specific nematodes in pats from both groups and some species
      were reduced in pats deposited 3, 7, and to a lesser extent, 14 days after
      treatment for the ivermectin group compared with pats from the levamisole group.
      These effects on dung fauna had no impact on dung degradation. The results of
      serial measurement of pat area, photographic evaluation, and determination of
      remaining dung weight and organic matter showed no difference between treatment
      group.

PMID- 7812317
TI  - A case of probable transplacental transmission of Wuchereria bancrofti
      microfilariae.
AB  - A case of transplacental transmission of Wuchereria bancrofti microfilariae is
      reported in endemic are of Bauchi State, Nigeria. The diagnosis was based on the
      history of illness, clinical symptoms, age of the child and presence of sheathed
      microfilariae of nocturnal periodic form of W. bancrofti in the peripheral blood
      films. Also the night blood sample collected from the child's mother revealed mf
      of W. bancrofti in addition to the unilateral elephantiasis of the hindlimb. The
      implication of this observation is stressed.

PMID- 7812318
TI  - Detection of Echinococcus coproantigens in stray dogs of northern Spain.
AB  - An enzyme-linked immunosorbent assay (ELISA) was assessed for its suitability to
      diagnostically detect Echinococcus coproantigens in fecal samples of dogs
      infected with E. granulosus. The specificity of the test was determined by
      investigating fecal samples from 177 Echinococcus-free dogs infected with Taenia
      spp., 41 dogs with non-taeniid helminths and 24 dogs free of helminth infections.
      An overall specificity of 97% was determined. The diagnostic sensitivity was in
      close association to the worm burden of infected individuals: when dogs harboured
      less than 100 worms, six from 21 samples (29%) were found to be positive in
      coproantigen ELISA, whereas sensitivity was much higher (23 ELISA-positive from
      25 samples = 92%) when dogs had more than 100 worms. Despite the relatively low
      average sensitivity (63%), the test enabled detection of more than 90% of the
      biomass of adult Echinococcus present in the respective dog populations.
      Conclusively, coproantigen detection allows diagnosis of most individual
      intestinal Echinococcus infections relevant for the egg contamination of the
      environment and is therefore a valuable tool to determine the relative prevalence
      of adult stage E. granulosus prevalence in a given endemic area.

PMID- 7812319
TI  - Learning from a distance: education choices.

PMID- 7812320
TI  - Realistic rostering.

PMID- 7812321
TI  - Violence at work: an ethical dilemma.

PMID- 7812322
TI  - Nurses must speak out.

PMID- 7812323
TI  - Adapting nursing to the cuts.

PMID- 7812324
TI  - Managing meningitis.

PMID- 7812325
TI  - Teaching clients well.

PMID- 7812326
TI  - How to be part of the union.

PMID- 7812327
TI  - Getting research off the ground.

PMID- 7812328
TI  - Preventing 'needlesticks'.

PMID- 7812329
TI  - The constant vision: quality of care.

PMID- 7812330
TI  - Promoting knowledge-based practice.

PMID- 7812332
TI  - Life after downsizing: strategies for organizational healing and revitalization.
AB  - In the midst of mergers, acquisitions, and restructuring, organizations are often
      resorting to painful cutbacks and downsizing. People at all levels are getting
      laid off. In many cases, tightening the belt is squeezing the very life out of
      the organization. Savings are often counterbalanced by the lack of productivity
      of a depressed and demoralized workforce. A structured intervention that
      addresses survivor issues is necessary for healing to occur. The future of the
      organization may depend on it.

PMID- 7812331
TI  - Malignant pleural effusion.
AB  - Pleural effusion is a frequent complication of malignant disease. With a
      realization of pathophysiological mechanisms, symptomatology, and specific care
      needs of patients, the nurse can make appropriate assessments and provide
      thorough and essential care to improve patient outcome.

PMID- 7812333
TI  - Breast self-examination: how nurses can influence performance.
AB  - Breast self-examination (BSE) is a detection technique that is performed on a
      regular monthly basis by only 25% to 35% of American women. The incidence of
      breast cancer is steadily rising. Mammography not only fails to detect some
      cancers but is not available to many women. BSE is an important self-care
      technique that nurses should teach all female patients, regardless of the
      setting.

PMID- 7812334
TI  - The self-defense mechanism of fever.
AB  - Body temperature is the result of a complex interaction of factors and serves as
      an important defense mechanism. A discussion of thermoregulation and fever
      development provides the basis for nursing actions with febrile patients.

PMID- 7812335
TI  - Reflex sympathetic dystrophy syndrome: a longitudinal study.
AB  - Reflex sympathetic dystrophy syndrome is a multi-symptom, multi-system syndrome
      which affects all age groups with the common, overriding complaint of severe,
      unrelenting, burning pain. Affecting millions worldwide, the illness trajectory
      is poorly understood. A large longitudinal patient study has yielded important
      preliminary findings, which have implications for nurses caring for a variety of
      patients in pain.

PMID- 7812336
TI  - Treating and preventing kidney stones.
AB  - Kidney stones usually develop when urine becomes concentrated and crystals form.
      These stones can lodge anywhere in the urinary system and cause severe pain. Most
      stones pass spontaneously, but 20% of all patients receive medical intervention.
      Noninvasive approaches and conventional surgery are used. Nurses assess and
      monitor patients through diagnosis and treatment, and teach patients how to avoid
      a recurrence.

PMID- 7812337
TI  - Outcomes measurement in clinical practice.
AB  - Although nurses contribute significantly to patient outcomes, there are few data
      documenting the nature or magnitude of that impact and how it may vary in
      different practice settings or geographic regions (Lang & Marek, 1992). Only when
      we move beyond the theoretical into the practical application of outcome
      evaluation and management will we be able to have a data-driven system to
      articulate nursing's contribution to patient outcomes. Making this application a
      reality requires the vision and talents of nurses in all roles from staff nurses
      to administrators.

PMID- 7812338
TI  - Assessing and treating depressed, medically ill patients.

PMID- 7812340
TI  - Advance directives: two years later.

PMID- 7812339
TI  - Hospital-based home care: delivering success.

PMID- 7812341
TI  - Amiodarone (Cordarone): what every nurse should know.

PMID- 7812342
TI  - Medical malpractice reform as a part of health care reform.
AB  - It appears that any health care reform will include tort reform. Since health
      care reform is aimed at reducing the cost of providing health care and since
      medical malpractice is believed to be a significant portion of that cost, any
      health care reform bill passed under the current political climate will most
      likely include provisions for limiting the costs associated with medical
      malpractice.

PMID- 7812343
TI  - Cancer biotherapy: 1993 to the millenium and more!

PMID- 7812344
TI  - Hormone receptor assays and their value in breast cancer therapy.

PMID- 7812345
TI  - c-erbB-2 DNA amplification and mRNA expression in human primary breast tumors and
      its relationship to other prognostic factors.
AB  - In order to evaluate the involvement of cerbB-2 oncogene in the etiology and
      progression of breast cancer, DNA samples from 157 primary human mammary
      carcinomas were subjected to Southern and dot blot analyses for the presence of c
      erbB-2 protooncogene alterations. None of 157 carcinomas analyzed showed c-erbB-2
      rearrangement. Amplification of the c-erbB-2 was found in 28.6% (45/157) of the
      samples. Gene expression could be analyzed in only 97 of these tumors. High
      levels of c-erbB-2 transcripts were detected in 25.7% (25/97) of the tumor RNA
      preparations. Although there was a good correlation between c-erbB-2
      overexpression and gene amplification, a significant proportion of the tumors
      showed overexpression in the absence of gene amplification or gene amplification
      without overexpression. A significant correlation between c-erbB-2 proto-oncogene
      alterations with the number of positive lymph nodes and tumor necrosis was found,
      suggesting that c-erbB-2 genetic alterations have a biological importance in the
      etiology of breast cancer.

PMID- 7812346
TI  - A phase I escalating-dose safety, dosimetry and efficacy study of radiolabeled
      monoclonal antibody LYM-1.
AB  - Thirteen patients with relapsed or refractory Non-Hodgkin's Lymphoma were treated
      with 131I-Lym-1 during the course of a dose escalation trial. Principal aims were
      to establish the maximum tolerated single dose (MTD), as well as to assess
      clinical and dosimetric effects of the MTD. Patients were eligible if > 25% of
      tumor cells bound Lym-1 on immunohistochemistry, stain intensity was +2/4 or
      greater and human anti-mouse antibody (HAMA) assay was negative.
      Radioimmunotherapy was performed with escalating doses at levels of 50 mCi, 65
      mCi/m2 and 80 mCi/m2 (50-139 mCi total). Patients were eligible for retreatment
      after 6-10 weeks if there was no severe toxicity, their disease was at least
      stable and HAMA remained negative. Three were retreated. Four have achieved
      partial responses which lasted 11, 11, 18 and 22 weeks. Acute toxicities included
      rigors (69%), fever (62%), nausea (46%), vomiting (46%), pruritus (23%),
      urticaria (23%), chest pain (23%) and bronchospasm (15%). HAMA developed in 3
      patients. Myelosuppression, manifested as thrombocytopenia and neutropenia, was
      dose-limiting and defined the single dose MTD at 65 mCi/m2. Plasma radioactivity
      clearance was biphasic, with a 0.9 hr alpha-T1/2 and a 19.8 hr beta-T1/2. At
      completion of Lym-1 infusion, a mean of 45% of the injected dose was recoverable
      in the circulation. Images obtained within the first 2 hours indicated mean
      hepatic and splenic uptake was 29% and 11%, respectively. Radiation absorbed
      doses to tumor ranged from 18-61 rads; mean doses to whole body ranged from 17 to
      71 rads.

PMID- 7812347
TI  - A pilot clinical and pharmacological study of intra-arterial infusion of
      thiotepa.
AB  - Fourteen patients with progressive localized tumors were treated on a clinical
      and pharmacological study with intra-arterial Thiotepa. A transfemoral
      percutaneous catheter was inserted into the major artery supplying the tumor. A
      venous catheter was inserted into the vein draining the tumor area for blood
      sampling. Doses of Thiotepa ranged from 0.3 mg/kg to 1.0 mg/kg. Courses were
      repeated monthly and doses of drug escalated as tolerated. Toxicity was mild and
      doses of drug at least up to 0.9-1.0 mg/kg were tolerable. Pharmacokinetic
      parameters suggest increasing binding of Thiotepa to tissue when the drug is
      administered by the intra-arterial route. Clinical responses were observed in a
      patient with melanoma and in another patient with unknown primary cancer.

PMID- 7812348
TI  - Clinical and pharmacological study of intrahepatic artery infusion of thiotepa.
AB  - Twenty patients with primary or metastatic liver cancer were treated on a
      clinical and pharmacological study with intrahepatic artery infusion of Thiotepa.
      Toxicity was tolerable and included nausea and fatigue. Uncommon side effects
      were myelosuppression, abdominal pain and anemia. One patient with gallbladder
      cancer had a partial response for 11 (+) months. Recommended dose of Thiotepa for
      future Phase II clinical trials is 1.0 mg/kg. Pharmacokinetics of intrahepatic
      Thiotepa revealed an extraction ratio similar to that reported for cisplatin. The
      data suggest increased hepatic clearance for Thiotepa either by binding or
      metabolism.

PMID- 7812349
TI  - Evaluation of a new test for colorectal neoplasms: a prospective study of
      asymptomatic population.
AB  - In a recent pilot study, we have suggested of potential usefulness of a new test
      (Shams' test) for screening colorectal (CR) cancer in Japan. Although the
      sensitivity of this test was remarkably high, its accurate specificity was
      unclear. The purpose of our present study is to evaluate the incidence of non
      specific reaction of Shams' test in the normal Japanese populations. We analyzed
      330 asymptomatic individuals, who were seen for annual health checkup, for the
      presence of the tumor marker D-Gal-B (1- > 3)-D-GalNAc in their rectal mucin. The
      rectal mucin was smeared on nitrocellulose membrane filter and developed by a
      sequential reaction of B-D-galactose oxidase and Schiff's reagent. Immunological
      fecal occult blood test (FOBT) was done in parallel. Extensive study by barium
      enema/total colonoscopy was indicated only for those who showed positive results
      with Shams' test or FOBT. A total of 271 individuals were negative, while 50 and
      9 had positive and equivocal (+/-) results, respectively. Subsequent barium enema
      and fiberoptic proctocolonoscopic examinations, which were available on 32 of 59
      cases, revealed 6 adenomatous polyps, one villous adenoma with focal severe
      atypia, and 4 cases of diverticular disease. Except for one patient with polyp, 6
      other patients harboring polyps were negative with immunological FOBT. The
      overall specificity of Shams' test was 92.2% (271/294). Based on these results
      and preceding reports, we concluded that Shams' test could be a useful tool in
      our strategy for early detection of CR neoplasms and precancerous lesions.

PMID- 7812350
TI  - Unique pancreatic carcinoma cDNA found via subtracted libraries with limited
      normal tissue and tumor from the same patient.
AB  - We have approached the problem of isolating clones unique to specific
      malignancies such as T-cell acute lymphoblastic leukemia (ALL) and pancreatic
      adenocarcinoma by using subtractive hybridization techniques. Our initial studies
      involved using normal donor tissue (i.e., normal blood donors for ALL and cadaver
      renal transplant donors for normal pancreatic tissue) and cultured malignant cell
      lines. It occurred to us that normal pancreatic tissue from the same patient
      source as that of the malignant tissue might subtract out normal sequences more
      readily and enrich clones unique to pancreatic adenocarcinoma because of
      patient/donor identity. Using such a method meant that the amounts of tissue for
      overcoming this obstacle. We constructed independent UNI-ZAP-XR cDNA libraries
      (normal and malignant) and used them to amplify either the normal or malignant
      cDNA prior to subtractive hybridization. We then obtained rescued single stranded
      cDNA from the malignant ZAP library. The RNA which was not hybridized was
      isolated. The process was repeated and a double subtraction was effected. The
      residual non-hybridized RNA was used as a template for first and second strand
      synthesis. After the EcoRI adaptors were ligated to the double stranded cDNA it
      was cloned into Lambda ZAP II arms to form a double subtracted malignant cDNA
      library. A subtracted probe was prepared from the double subtracted cDNA library.
      Single stranded cDNA was rescued, double stranded plasmid was made, the plasmid
      DNA was digested with EcoRI, the digested DNA was run on a 1% SeaPlaque gel, and
      the insert cDNA was recovered using Ultra-Free MC and Ultra-Free Probind filters.
      The subtracted malignant cDNA library was probed with the subtracted probe and
      with normal cDNA (obtained from the normal ZAP library) and those plaques which
      were positive per the subtracted probe and negative per the normal cDNA were
      isolated; their cDNA inserts are being further characterized.

PMID- 7812351
TI  - Reversal of C1300 murine neuroblastoma multidrug resistance by cremophorEL, a
      solvent for cyclosporin A.
AB  - We previously developed a homoharringtonine resistant C-1300 neuroblastoma cell
      line with cross-resistance to adriamycin and increased levels of p-glycoprotein,
      and showed that drug resistance could be reversed in this cell line by
      cyclosporin A. The present study shows that cremophor EL, a parenteral vehicle
      for cyclosporin A, can also completely reverse this multidrug resistance in a
      clonogenic assay system. Cremophor EL incubated with resistant cells for up to
      six days did not reduce levels of p-glycoprotein. Intracellular homoharringtonine
      analysis using HPLC revealed increased drug accumulation in resistant cells
      treated with cremophor EL. The increased drug level was not due to blocking of
      drug efflux commonly seen in other multidrug resistant models. The data suggest
      that resistance modulation with cyclosporin A should be interpreted with caution
      when cremophor EL is a solvent. Our work suggests cremophor EL, a relatively
      nontoxic lipophylic solvent, may have a direct effect on membrane permeability,
      although other mechanisms cannot be ruled out.

PMID- 7812352
TI  - Sensitization of P388 murine leukemia cells to epirubicin cytotoxicity by
      reserpine.
AB  - Reserpine, the crystalline active substance isolated from the Rauvolfia plant,
      produces a characteristic vasodepressor effect in hypertensive patients. Apart
      from its antihypertensive property, reserpine also possesses transquillising and
      vasodepressor action, hence it is employed as supportive therapy in the treatment
      of cardiac disorders. Doxorubicin is a potent anticancer agent, the use of which
      is limited by its cumulative dose-dependent cardiotoxicity. Epirubicin is a
      derivative of doxorubicin having more favourable therapeutic index than
      doxorubicin and possessing less hematologic and cardiac toxicity at comparable
      doses. The data presented in this paper show the effect of reserpine as a
      chemosensitizer, when used in combination with epirubicin on P388 murine leukemia
      cells sensitive (P388/S) and resistant to doxorubicin (P388/DOX) cells.
      Inhibition of 3H-TdR incorporation into DNA was used as an index of the cytotoxic
      effects of drug when used alone or in combination. The combination of reserpine
      (1 microM) and epirubicin (1.7, 8.6 and 17.2 microM) indicated a significant
      enhancement in the DNA biosynthesis inhibition in P388/S and P388/DOX cell lines.
      The most prominent feature of the multidrug-resistant cell is the reduced
      accumulation of the drug intracellularly. P388/DOX cells showed less accumulation
      of epirubicin in the cell as compared to that of the parental cell line. Further
      studies demonstrated that reserpine significantly enhanced the intracellular
      accumulation of epirubicin in both the cell lines. The nature of DNA damage
      caused by the combination of reserpine and epirubicin was irreversible when
      studied in P388/DOX cell line. The combination of reserpine (5mg/kg) and
      epirubicin (1mg/kg) significantly potentiated the antitumor activity of
      epirubicin in P388/DOX tumor bearing mice. These studies suggest that reserpine
      can be used as an adjuvant in the cancer chemotherapy to potentiate the
      antiproliferative activity of anticancer drugs.

PMID- 7812353
TI  - Cytokines and the rational choice of immunological adjuvants.

PMID- 7812354
TI  - Human anti-mouse antibody response in cancer patients following single low-dose
      injections of radiolabeled murine monoclonal antibodies.
AB  - We examined the human anti-mouse antibody (HAMA) response in 61 cancer patients
      following a single, diagnostic injection of any one of ten 111In conjugated
      murine monoclonal antibodies. Between 1 and 22 mg of antibody containing 1-5 mCi
      111In was administered. The populations studied included 30 patients with
      colorectal carcinoma (four different antibodies), 22 with malignant melanoma
      (four antibodies), and nine with prostate cancer (two antibodies). Forty-one
      percent of the patients developed HAMA within 14 days. Three patients (5%)
      developed an IgM response, five patients (8%) developed an IgG response, and 17
      patients (28%) developed both IgM and IgG. Only 27% of the patients with colon
      cancer developed HAMA, compared to 55% of the melanoma patients and 56% of the
      prostate cancer patients. There were no correlations among injected dose, various
      clinical parameters, and HAMA response. There were variations in the HAMA
      response to different monoclonal antibodies, but population samples were too
      small to infer significance. Most of the HAMA responses had a significant
      proportion of idiotypic or isotypic specificity. Only 1/6 patients who were HAMA
      negative after the first infusion developed HAMA following subsequent infusions
      of the same monoclonal antibody. Our data demonstrate that a significant percent
      of cancer patients develop HAMA following a single, low-dose injection of a
      radiolabeled monoclonal antibody for diagnostic purposes. This may have important
      implications for the future therapeutic use of monoclonal antibodies in such
      patients.

PMID- 7812355
TI  - Identification of melanoma cell surface antigens immunogenic in mice.
AB  - Active immunization to B16 melanoma cells or vaccines induces anti-melanoma
      immune responses in syngeneic mice. The immunogenic antigens stimulating immunity
      to this tumor have not been identified. In this study we detected several B16
      melanoma antigens immunogenic in syngeneic mice using as probes antimelanoma
      antibodies induced by immunization to B16 melanoma vaccines. These antigens were
      identified by SDS-PAGE and autoradiographic analysis of specific
      immunoprecipitates. They were cell-surface components with approximate molecular
      weights of 41, 46, 50, 75, 80, and 104 KD. All these antigens were expressed by
      syngeneic and xenogeneic melanomas and by some unrelated syngeneic tumors but not
      by normal syngeneic cells, xenogeneic melanocytes, or by B16 melanoma cells
      obtained from fresh tumors or grown in defined medium. The antigens were distinct
      from murine viral antigens expressed by B16 melanoma cells and from components of
      the culture medium used to grow cells for vaccine production. These results
      indicate that several B16 melanoma cell-surface antigens are immunogenic in
      syngeneic mice. Expression of these antigens appears to be related to malignant
      transformation as they were found on all melanomas studied, and some other
      cancers, but not on normal cells.

PMID- 7812356
TI  - Increased oxygen tensions influence subset composition of the cellular immune
      system in aged mice.
AB  - In acute and chronic experiments, each of eight groups of aged mice were assigned
      separately to different pressures of oxygen to which it was to be exposed.
      Lymphocytes from spleen, thymus, and peripheral blood were analyzed following
      oxygen exposure. Subset populations changed depending on the oxygen tension.
      Variable changes were observed in total numbers of lymphocytes, lymphocyte
      subsets, B cells, and macrophages depending on the organ studied and the oxygen
      pressure to which the mice were exposed. There were differences between acute and
      chronic exposure suggestive of adaptation to environmental stressors. The
      suggestion is made that the immune system has a reserve capacity that can be
      influenced by oxygen and, thereby, theoretically capable of being
      pharmacologically manipulated to assist patients with altered immune systems to
      promote defense mechanisms or, under certain circumstances, reduce autoimmunity.
      It is hypothesized that an underlying hypoxia may be involved in the age
      associated decline in the immune system.

PMID- 7812357
TI  - Oxidative stress relief for cancer-bearing hosts by the protein-bound
      polysaccharide of Coriolus versicolor QUEL with SOD mimicking activity.
AB  - The protein-bound polysaccharide of Coriolus versicolor QUEL (PS-K) expresses the
      mimetic activity of superoxide dismutase (SOD). Human cancer patients usually
      suffer from oxidative stress (OS). Examination was made to determine the capacity
      of this drug with SOD mimetic activity for relieving OS. Rats transplanted with
      Walker 256 fibrosarcoma showed OS on day 12. After confirming high levels of OS
      on day 13, PS-K50 mg/kg was intraperitoneally administered, and prompt decrease
      in O2-release from RBC was noted. The drug ceased to have any effect 24 hours
      following the first inoculation. Average OS in human cancer patients was found
      twice that in healthy persons. In human cancer patients perorally administered PS
      K3.0 g/day, OS decreased to the normal level one day after the initial
      administration. Plasma lipid peroxide (LPO) in cancer patients treated with PS-K
      for 28 days increased and withdrawal of the drug led to decreased LPO.

PMID- 7812358
TI  - Suppression of cancer cell growth in vitro by the protein-bound polysaccharide of
      Coriolus versicolor QUEL (PS-K) with SOD mimicking activity.
AB  - The protein-bound polysaccharide of Coriolus versicolor QUEL (PS-K) expresses the
      mimicking activity of superoxide dismutase (SOD). Examination was made of the
      suppressive effects of PS-K on cancer cell lines cultured in vitro. The SOD
      activity of LLC-WRC-256 (Walker 256 fibrosarcoma) cell lines was less than that
      of NRK-49F (rat normal kidney fibroblast), H4-II-E (rat hepatoma) and H4-II-E-C3
      (rat hepatoma) cell lines. This activity in Walker 256 fibrosarcoma cells
      increased by 3.6 times and H2O2 concentration, by 2.56 times by PS-K 500
      micrograms/ml. Cell proliferation was consequently suppressed and living cells
      decreased to less than 50% of the cells cultured without PS-K. Catalase and
      glutathione peroxidase activity changed little by PS-K. The sensitivity of cancer
      cells to PS-K can be predetermined based on SOD activity in tumor tissue.

PMID- 7812359
TI  - T/Tn antigen vaccine is effective and safe in preventing recurrence of advanced
      human breast carcinoma.
AB  - For nearly 20 yrs, we used T/Tn antigen vaccine in safe, specific, effective,
      long-term intradermal vaccination against recurrence of advanced breast
      carcinoma. Treatment is ad infinitum. All 18 breast carcinoma patients treated,
      pTNM Stages IV (6), III (6), and II (6), survived > 5 yrs postoperatively; 10
      survived > 10 to > 18 yrs; of the latter, three patients each are Stages III and
      IV. Five additional 5 yr survivors have not yet reached 10 yrs. The probability
      that our survival results are due to chance, with NCI "1991 Standard PDQ Data" as
      control, for all three stages taken together is: 5-yr survival: p < 1 x 10(-8);
      10-yr survival: p < 1 x 10(-5). There were no untoward side effects. The
      vaccination area presented as a delayed-type hypersensitivity reaction, but at
      variance with the PPD reaction, with significant inflammation, increase of helper
      T lymphocytes and decrease of the T suppressor/cytotoxic cell ratio.

PMID- 7812360
TI  - Phase I study of interleukin-2 combined with interferon-alpha and 5-fluorouracil
      in patients with metastatic renal cell cancer.
AB  - Interferon-alpha (IFN-alpha) and interleukin-2 (IL-2) each has produced a 15%-20%
      response in metastatic renal cell cancer. Combining IFN-alpha with either IL-2 or
      5-fluorouracil (5-FU) enhanced IFN-alpha activity. We have therefore conducted a
      Phase I Study combining IL-2, IFN-alpha, and 5-FU. The patients were continuously
      infused with IL-2 (1-3 x 10(6) u/m2) and 5-FU (600-750 mg/m2) for a 5-day period
      every 28 days, and IFN-alpha (4-5 x 10(6) u/m2) was injected subcutaneously
      daily. Lymphokine-activated killer (LAK) and natural killer (NK) cell activity
      was measured on days 0 and 8. Twenty-one patients received 76 courses. All
      primary tumors were controlled by surgery (81%) or angioinfarction. Hematologic
      toxicity was mild; median nadir of platelets was 117 K/microL and of granulocytes
      was 1.2 K/microL. Dose-limiting toxicity included mucositis, liver damage, and
      hypotension. No treatment-related death occurred, and only one patient required
      intensive-care-unit support. Two patients had an objective response, one of which
      was a complete response. Increased LAK cell and NK cell activity occurred at all
      IL-2 dose levels. Simultaneous delivery of IL-2, IFN-alpha, and 5-FU is safe and
      shows antitumor and biologic activity. 5-FU did not appear to suppress IL-2
      induced LAK and NK cell activation. Maximum tolerated dose of the three-drug
      combination is IL-2, 2 x 10(6) u/m2, 5-FU 600 mg/m2, and IFN-alpha, 4 x 10(6)
      u/m2.

PMID- 7812361
TI  - Generation of specific antitumor cytotoxic T-lymphocytes in monoculture can be
      inhibited by T-suppressors from tumor-bearing mice.
AB  - A new model for the generation of specific antitumor cytotoxic T lymphocytes
      (CTL) was proposed. In contrast to other models, it allows to generate secondary
      effector CTL (CTL-2) without tumor stimulator cells in vitro (in monoculture).
      C57BL/10 mice or/and C57BL/6 mice were immunized by injection with gamma
      irradiated syngeneic tumor cells into the footpads. For estimation of cytotoxic
      activity, chromium-51 release assay was used. It has been shown that effector CTL
      were absent in the lymph nodes after 1-fold as well as 2-fold immunization.
      Cytotoxic cells have not been found in 1-fold immunization even after maturation
      of the lymphocytes in monoculture. Specific CTL were detected only after
      secondary immunization and subsequent cultivation in vitro. Effector cells had
      Thy1.2, CD8+, CD4- phenotype. Presence in vitro of exogenous recombinant
      interleukin 2 (rIL-2) was needed for the generation of CTL-2 against Mech-11
      sarcoma but not against EL4 lymphoma. The spleen cells from B10 mice with
      progressively growing Mech-11 tumor specifically suppressed the maturation of CTL
      2 against Mech-11 in monoculture. Since suppression took place in the presence of
      exogenous rIL2 in monoculture, it was suggested that suppression was not resulted
      by negative influence of the suppressor cells upon endogenic IL-2 production. The
      treatment of the suppressor cells with monoclonal antibody (Mab) against Thy1.2
      as well as against CD4 or CD8 markers plus complement (C') considerably decreased
      Ts activity. Obviously, two distinct subsets of T-lymphocytes were required for
      suppression.

PMID- 7812362
TI  - Gene therapy for B-cell lymphoma in a SCID mouse model using an immunoglobulin
      regulated diphtheria toxin gene delivered by a novel adenovirus-polylysine
      conjugate.
AB  - Despite advances in conventional therapy, many lives continue to be lost to
      common forms of B-cell cancers, including leukemias, lymphomas and multiple
      myeloma. We propose a novel approach to therapy of such cancers using controlled
      expression of a diphtheria toxin gene (DT-A) to kill malignant cells. We have
      previously demonstrated selective killing of various cell types, in vitro and in
      vivo, by cell-specific, transcriptionally controlled expression of this gene.
      Organ-specific ablation in otherwise healthy transgenic mice has convincingly
      demonstrated the exquisite specificity achievable by this technique. In the
      studies now described, DT-A was delivered in vitro and in vivo using a novel gene
      delivery system employing DNA physically attached to the exterior of adenovirus.
      After demonstrating the efficacy of gene delivery to Epstein-Barr virus
      transformed human B-cells in vitro, in vivo work was performed using a SCID mouse
      model for B-cell lymphoma, in which protection against tumor was observed. The
      concepts of tissue-regulated toxin gene therapy, and this novel adenovirus gene
      delivery system are discussed.

PMID- 7812363
TI  - In vitro effects of pentoxifylline and doxorubicin on cell survival and DNA
      damage in sensitive and MDR-P388 leukemia cells.
AB  - The utility of chemosensitizers to improve efficacy of chemotherapy is now
      gaining importance. This report investigated whether an active hemorheological
      agent, pentoxifylline (PTX), can circumvent drug resistance in parental (P388/S)
      and multidrug resistant (P388/DOX) P388 leukemia cells. For detection of
      doxorubicin (DOX) resistance and reversal of this resistance by PTX, the
      incorporation of nucleic acid precursor was measured after addition of DOX and
      PTX, respectively. The effect of PTX on the induction of DNA strand breaks by DOX
      was also examined. Increased fragmentation of DNA was illustrated in P388/DOX
      leukemia cells exposed to the combination of DOX and PTX. The most prominent
      feature of the multidrug-resistant cell is the reduced accumulation of the drug
      intracellularly. P388/DOX cells showed less accumulation of DOX in the cell as
      compared to that of the parental cell line. Further studies demonstrated that PTX
      significantly enhanced the intracellular accumulation of DOX in both the cell
      lines. These studies warrant the use of PTX as an adjuvant in cancer
      chemotherapy.

PMID- 7812364
TI  - Chinese medicinal herbs inhibit growth of murine renal cell carcinoma.
AB  - Tumors are known to produce factors suppressing immune functions. We previously
      showed that a murine renal cell carcinoma (Renca) suppressed macrophage function
      in vitro and that this suppression was abolished by co-incubation with extracts
      of two Chinese medicinal herbs. We now report that these phytochemicals are
      capable of inhibiting growth of Renca in vivo. BALB/c mice were transplanted
      intraperitoneally (IP) with 1-2 x 10(5) Renca cells. One day after tumor
      transplant, mice were randomized into two groups. One group was treated IP, daily
      for 10 days, with 100 microliters of phytochemicals containing 500 micrograms
      each of Astragalus membranaceus and Ligustrum lucidum, while the other group
      received saline as controls. A cure rate of 57% was obtained with these
      phytochemicals when the initial tumor load was 2 x 10(5), and 100% when the
      initial tumor load was 1 x 10(5). Additional experiments were performed to
      investigate the mechanisms involved in this protection. Splenic macrophages from
      tumor-bearing mice were shown to have depressed chemiluminescent oxidative burst
      activity, and this depression was restored with phytochemical treatment.
      Splenocytes from mice transplanted with Renca responded less favorably to
      interleukin-2 (IL-2) in generating lymphokine-activated killer (LAK) cells; again
      this depression was restored with phytochemical treatment. Our data suggest that
      these phytochemicals may have exerted their antitumor effects via augmentation of
      phagocyte and LAK cell activities.

PMID- 7812365
TI  - Suppressive effects on cancer cell proliferation of the enhancement of superoxide
      dismutase (SOD) activity associated with the protein-bound polysaccharide of
      Coriolus versicolor QUEL.
AB  - The protein-bound polysaccharide of Coriolus versicolor QUEL (PS-K) expresses
      superoxide dismutase (SOD) mimicking activity. Examination was made of the
      suppressive effects of PS-K on cancer cell lines cultured in vitro. SOD activity
      of incorporated PS-K was 5.88 u/mg in LLC-WRC-256 (Walker 256 fibrosarcoma) cells
      and 4.73 u/mg in NRK-49F (rat normal kidney fibroblast) cells. SOD activity in
      both cell types was enhanced about 7-8 times that of the original PS-K. PS-K was
      not incorporated into H4-11-E or H4-11-E-C3 (rat hepatoma) cells. SOD activity of
      1 mg/ml PS-K incubated with cell homogenates of LLC-WRC-256 cells for 6 hours
      increased from 0.68 u/mg to 1.35 u/mg. SOD activity of PS-K 1 mg/ml in 0.05 M
      phosphate buffer incubated with 50 microM NADPH increased from 0.68 u/mg. The
      consumption of NADPH at the same concentration was confirmed
      spectrophotometically by incubation with PS-K. The mechanism for the enhancement
      of SOD activity associated with PS-K is considered to be collaboration with NADPH
      as an electron donor in the cytoplasm of cancer cells whose SOD and coupling
      enzyme activities are significantly lower than in normal cells.

PMID- 7812366
TI  - Cancer research: does it deliver for the patient?

PMID- 7812367
TI  - A bleak future for gynecological laparoscopic surgery?

PMID- 7812368
TI  - Costs associated with endoscopic surgery.

PMID- 7812369
TI  - Laser versus electrosurgery: what to use in laparoscopy.

PMID- 7812370
TI  - Gasless laparoscopy eliminates complications caused by pneumoperitoneum.

PMID- 7812371
TI  - Laparoscopic treatment of endometriosis using the radially expanding dilator.

PMID- 7812372
TI  - Information overload and medical progress: when is enough too much?

PMID- 7812373
TI  - Can laser safety be taught to student nurses?

PMID- 7812374
TI  - Use of laparoscopic nissen fundoplication increasing steadily.

PMID- 7812375
TI  - Rates of laparoscopic cholecystectomy increase dramatically.

PMID- 7812376
TI  - Laser technology has waned in some specialties during the past 2 years.

PMID- 7812377
TI  - Perspective: an ever-changing world.

PMID- 7812379
TI  - Surgeon and assistant must work closely during laparoscopic pelvic floor support
      repairs.

PMID- 7812380
TI  - Lap chole safe, effective for elderly patients.

PMID- 7812381
TI  - Laser resource directory.

PMID- 7812378
TI  - Intra-abdominal smoke may endanger laparoscopy patients.

PMID- 7812382
TI  - An interview with Kathy Rada, R.N., marketing manager, Surgilase, Warwick, RI.

PMID- 7812384
TI  - Reusable versus single-use laparoscopy instruments: who is responsible for
      patient safety?

PMID- 7812383
TI  - Gasless laparoscopy with mechanical peritoneal distention.

PMID- 7812385
TI  - Endoscopic urinary stone management with the alexandrite laser.

PMID- 7812386
TI  - Designing research: basics of survey construction.
AB  - The survey/questionnaire can be a useful tool for gathering information. A novice
      can construct an effective questionnaire, if basic construction format is
      understood and rules for construction and writing are followed. As experience is
      gained, the instrument design can become more complex. Anyone can collect useful
      information. Collected data may be directly applied to practice, used as a pilot
      project, or be a stand-alone project for publication. The ability to effectively
      design and use this instrument is an important skill for researchers and
      clinicians.

PMID- 7812387
TI  - Stab evulsion phlebectomy: a minimally invasive approach for treating varicose
      veins.

PMID- 7812388
TI  - An innovative approach to endoscopic instrumentation.

PMID- 7812389
TI  - Brachytherapy: a minimally invasive option for treating prostate cancer.

PMID- 7812390
TI  - Marketing your laser program in the '90s on a limited budget.

PMID- 7812391
TI  - Riding the superhighway of education with video teleconferencing.

PMID- 7812392
TI  - Conducting a laser specialist program for multiple hospitals.

PMID- 7812393
TI  - Health care reform.

PMID- 7812394
TI  - Perspective: nursing's role in health care reform.

PMID- 7812395
TI  - Robotic arm returns direct scope control to surgeon.

PMID- 7812397
TI  - Another kind of smoke hazard.

PMID- 7812396
TI  - Laparoscopic cholecystectomy in pregnancy: a brief review of clinical experience.

PMID- 7812398
TI  - The effects of smoke plume generated during laser and electrosurgical procedures.

PMID- 7812400
TI  - Perspective: high-tech can be affordable.

PMID- 7812399
TI  - Health care reform activities.

PMID- 7812402
TI  - Nursing and health care reform: an interview with AORN president Jane Rothrock.

PMID- 7812401
TI  - Microendoscopy: tiny scopes take laparoscopic procedures into the office.

PMID- 7812403
TI  - Pediatric laparoscopy gaining support.

PMID- 7812404
TI  - An interview with Nissa Partain DeLisle, R.N., B.S.N., C.N.O.R., independent
      consultant, Powder Springs, GA.

PMID- 7812405
TI  - Why the use of lasers in gynecologic laparoscopy has declined.

PMID- 7812406
TI  - Laparoscopic hernia repair.

PMID- 7812407
TI  - Developing a mobile laser service.

PMID- 7812408
TI  - Thoracoscopic treatment of emphysema with the Nd:YAG laser.

PMID- 7812409
TI  - The Laser Educational Network: a New England initiative.

PMID- 7812410
TI  - A 40-year history of overweight children in Stockholm: life-time overweight,
      morbidity, and mortality.
AB  - We describe the 40-year weight history and adult morbidity and mortality in a
      cohort of 504 overweight children, aged 2 months to 16 years, who were admitted
      for investigation of their overweight to four children's hospitals in Stockholm
      between 1921 and 1947. Follow-up information was gathered by questionnaire at 10
      year intervals, most recently in 1980-1983 (n = 458), on weight history (based on
      the body mass index (BMI = kg/m2)), as well as prevalence of cardiovascular
      disease (n = 143), diabetes (n = 39), and cancer (all types (n = 20)), reported
      during the 40 years of follow-up, and mortality from all causes (n = 55),
      determined from death certificate. The sample of overweight children remained
      overweight as adults; after age 55 years, the BMI began to decline for both
      genders. Female subjects were heavier than their male counterparts from
      postpuberty onward. Subjects who died by the 40-year follow-up and those
      reporting cardiovascular disease were significantly (P < or = 0.05) heavier at
      puberty and in adulthood than were healthier subjects. There was a marked
      increase in the BMI between postpuberty and age 25 among those who subsequently
      died, those who developed cardiovascular disease, and particularly among those
      who developed diabetes (P < or = 0.001). In contrast, those reporting cancer had
      a lower BMI throughout adulthood than those who did not. We conclude that
      overweight in adolescence may continue into adulthood and may be associated with
      subsequent adverse health outcomes.

PMID- 7812411
TI  - Measurement of 13CO2 in expired air as an index of compliance to a high
      carbohydrate diet naturally enriched in 13C.
AB  - The aim of this study was to determine whether breath 13CO2 measurements could be
      used to assess the compliance to a diet containing carbohydrates naturally
      enriched in 13C. The study was divided into two periods: Period 1 (baseline of 4
      days) with low 13C/12C ratio carbohydrates. Period 2 (5 days) isocaloric diet
      with a high 13C/12C ratio (corn, cane sugar, pineapple, millet) carbohydrates.
      Measurements were made of respiratory gas exchange by indirect calorimetry,
      urinary nitrogen excretion and breath 13CO2 every morning in post-absorptive
      conditions, both in resting state and during a 45-min low intensity exercise
      (walking on a treadmill). The subjects were 10 healthy lean women (BMI 20.4 +/-
      1.7 kg/m2, % body fat 24.4 +/- 1.3%), the 13C enrichment of oxidized carbohydrate
      and breath 13CO2 were compared to the enrichment of exogenous dietary
      carbohydrates. At rest the enrichment of oxidized carbohydrate increased
      significantly after one day of 13C carbohydrate enriched diet and reached a
      steady value (103 +/- 16%) similar to the enrichment of exogenous carbohydrates.
      During exercise, the 13C enrichment of oxidized carbohydrate remained
      significantly lower (68 +/- 17%) than that of dietary carbohydrates. The
      compliance to a diet with a high content of carbohydrates naturally enriched in
      13C may be assessed from the measurement of breath 13CO2 enrichment combined with
      respiratory gas exchange in resting, postabsorptive conditions.

PMID- 7812413
TI  - An insight into the personal and cultural significance of weight and shape in
      large Samoan women.
AB  - The aim of this work was to investigate the personal and cultural significance of
      body weight and shape for women in Western Samoan culture. A cross cultural study
      was carried out of Western Samoan and Australian women comparing responses to the
      Body Attitude Questionnaire (BAQ). The work was carried out in a tertiary
      education institution and an occupational setting in Apia, Western Samoa, and on
      community residents in Adelaide, South Australia. The subjects were 70 volunteer
      female respondents from Western Samoan educational and occupational settings,
      individually matched for weight and height with 70 respondents from a South
      Australian random community setting. The psychometric properties of the BAQ, as
      completed by the Western Samoan respondents, were found to be similar to those
      for Australian women. Samoan women who were biologically overweight, felt as fat
      and had similar feelings about lower body fatness as their identical weight
      Australian counterparts. They, however, showed highly significantly less salience
      of fatness than the Australian sample, indicating that fatness is not a pre
      occupying in Samoans as it is in Australian women. Despite this apparent non
      concern over their fatness, Samoan women were significantly more disparaging
      about their bodies than their Australian counterparts. The other significant
      finding from this cross-comparative study, was that large Samoan women felt more
      attractive and much stronger and fitter than their Australian counterparts. It
      was concluded that Samoan women's body-related attitudes can be studied using
      techniques and concepts originating in the west, but the specific concerns of
      Samoan women need to be explored in further detail.

PMID- 7812412
TI  - Familial and environmental influences on body composition and body fat
      distribution in childhood in southern Italy.
AB  - The aim of this paper was to evaluate the factors affecting body fat excess and
      distribution in prepubertal age. A cross-sectional survey was carried out on
      children attending the 4th grade of a primary school in Naples. Eighty-eight per
      cent of the total sample was examined: 52 girls, 58 boys; mean age = 9.6 yrs
      (s.e. +/- 0.10). Each child underwent a medical examination, anthropometric
      measurements and bio-impedance analysis of body composition. The parents were
      asked to fill in a questionnaire that included demographic data, family history,
      parent's weight and height, child's perinatal history and his or her involvement
      in sports activities. Data were analyzed by multiple linear regression. The
      results showed a direct correlation between parental BMI and children's
      anthropometric measurements: the children's BMI correlated with the fathers' (P =
      0.02) and mothers' BMI (P = 0.027); the children's waist/hip ratio correlated
      with the fathers' BMI (P = 0.07); the children's subscapular skinfolds correlated
      with the father's (P = 0.07) and mothers' BMI (P = 0.02); the children's triceps
      skinfolds correlated with the fathers' BMI (P = 0.004). Among congenital factors,
      sex was shown to be correlated with the children's waist/hip ratio (P = 0.05)
      with a lower ratio in the female, indicating a sex influence on body fat
      distribution even in prepubertal age. The children's BMI correlated with their
      waist/hip ratio (P = 0.001). Children's systolic blood pressure showed a positive
      correlation with triceps (P = 0.04) and subscapular (P = 0.05) skinfolds
      thickness % FAT-PLI (P = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7812414
TI  - Familial aggregation and heritability of waist-to-hip ratio in adult women: the
      Iowa Women's Health Study.
AB  - The aim of this study was to assess evidence that genetic factors influence body
      fat distribution. First-degree relatives of 324 cancer-free females in a
      population-based prospective study of 41,837 women (99% white) between the ages
      of 55 and 69 at baseline in 1986 were studied. A total of 396 living sisters
      (mean age 65.7 years) and 446 living daughters (mean age 41.2 years) were
      identified through a mailed 'family tree' questionnaire sent to each participant.
      Family members were mailed a questionnaire to obtain self-reported measures of
      current height and weight. A paper tape measure and written instructions were
      enclosed to obtain waist and hip circumferences. The age-adjusted mother
      daughters correlations for waist-to-hip ratio and body mass index (kg/m2) were
      0.19 and 0.23, respectively (P < 0.05 using Fisher's z-transformation). The
      corresponding sister-sister correlations were 0.23 and 0.19, respectively (P <
      0.05). The sister-sister correlations were not significantly different from the
      mother-daughter correlations. After adjustment for body mass index the mother
      daughter correlation for waist-to-hip ratio increased to 0.20 and the sister
      sister correlation increased to 0.26. These familial correlations suggest that
      genes and common environment may contribute 40 to 50% of the total variance of
      waist-to-hip ratio in white women in the Midwest.

PMID- 7812415
TI  - Body weight, fat distribution and the menopausal status in women. The VMH
      Collaborative Group.
AB  - Since sex hormones are involved in the regulation of body composition and adipose
      tissue metabolism, in this study we investigated whether menopause may alter body
      weight and fat distribution in women. Data were obtained from the Virgilio
      Menopause-Health Study, which is a longitudinal epidemiological project aimed at
      investigating the relationship between menopause and related plasma hormonal
      concentrations, body weight, fat distribution and health. Only data from the
      first cross-sectional examination are presented. Out of the 952 women living in
      the town of Virgilio, Mantua (Italy) and born between January 1st, 1932 and
      December 31st, 1946, 596 (62.6%) participated in the study. Since incomplete data
      were present in 19 women, 577 was the final sample size available for statistical
      analysis. The protocol included a collection of blood for hormones and
      biochemistry, a full clinical history with socioeconomic and personal
      information, drug use, smoking, dietary and physical activity habits, and several
      anthropometric measurements. According to the clinical and hormonal status, 160
      women were classified as pre-menopausal, 124 as peri-menopausal and 293 as post
      menopausal. After adjusting for age, we found that body mass index (BMI) was
      significantly higher in peri-menopausal than in pre-menopausal women and remained
      slightly, but again significantly, higher in post-menopausal women. Although
      waist-to-hip and waist-to-thigh ratios increased significantly and progressively
      from pre- to post-menopause, any difference was not significant after adjusting
      for age. Diet, physical activity and smoking habits did not explain the
      difference in BMI values. No difference was found in the use of estro-progestagen
      compounds between the groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7812417
TI  - Changes in glycogen metabolism in liver of gold thioglucose injected mice during
      the development of obesity.
AB  - A study of glycogen metabolism in the liver has been carried out in gold
      thioglucose (GTG) injected mice during the development of obesity. In GTG obese
      mice, overt obesity, hyperglycaemia and hyperinsulinaemia had developed by 6
      weeks after the injection of GTG. Beyond 6 weeks after GTG injection, the gain of
      body weight and increment in serum glucose and insulin levels with age in obese
      mice were not obvious when compared with those of age-matched control animals.
      The glycogen concentration, total glycogen storage, activity of glycogen synthase
      R and activity of phosphorylase a in the liver from GTG obese mice were
      significantly greater than those in lean mice from 2-4 weeks after GTG injection
      and remained higher thereafter. These results demonstrate that the increased
      liver glycogen storage and increased activity of glycogen synthase and
      phosphorylase occur early in the development of obesity and at a similar time to
      previously reported increases in pyruvate dehydrogenase activity (Caterson et al.
      (1987) Biochem. J. 243, 549-553) and lipid synthesis in liver (Cooney et al.
      (1989) Biochem. J. 259, 651-657). The emergence of these abnormalities in
      glycogen metabolism early in the development of obesity may contribute to the
      establishment of glucose intolerance and insulin resistance in this model of
      obesity which became apparent at approximately the same time after GTG injection.

PMID- 7812419
TI  - Measured and predicted total and visceral adipose tissue in women. Correlations
      with metabolic parameters.
AB  - The aim of this study was the verification of the clinical utility of predictive
      equations for total and intra-abdominal adipose tissue areas. Formulas were
      calculated using computed tomography (CT) as the gold standard. Ninety-three
      females were randomly divided into two groups. The predictive equation group was
      used to calculate the predictive equations for computed tomography adipose tissue
      areas at the L4-L5 level. These equations were then used to predict total and
      intra-abdominal adipose tissue area in the validation group. Correlations were
      made between metabolic parameters and both measured and calculated areas and
      single predictors. The following measurements were carried out: age,
      weight/height ratio, body mass index, waist, hip, waist/hip ratio, ultrasound
      measurement of intra-abdominal distance between abdominal muscle and aorta,
      sagittal abdominal diameter by CT, adipose tissue intra-abdominal area by CT,
      total abdominal adipose tissue area by CT. Blood glucose and insulin both fasting
      and after glucose load. Fasting cholesterol and triglycerides. The best
      predictors of total and visceral adipose tissue areas were, respectively:
      weight/height ratio and ultrasound intra-abdominal measurement. Correlations
      between metabolic parameters and adipose tissue areas both as measured and as
      calculated by predictive equations were quite similar. Correlations between
      metabolic parameters and single best predictors of measured adipose tissue areas
      also gave the same results. Some simple and safe anthropometric measurements can
      be used, instead of total and visceral adipose tissue area as assessed by CT,
      when studying associations between adipose tissue and metabolic parameters on
      sufficiently large groups of patients.

PMID- 7812418
TI  - Factors influencing energy intake of rats fed either a high-fat or a fat mimetic
      diet.
AB  - The aim of this study was to compare the effects of chronic feeding of a high-fat
      diet and a diet containing a fat mimetic on energy intake, body composition and
      tissue metabolism of mature female Sprague Dawley rats. Rats were fed a control,
      25% kJ fat, diet for 10 days. Preference for this diet compared with a high-fat,
      45% kJ fat, or fat mimetic, 25% kJ fat, diet was determined by offering rats two
      diets, in random order, for a period of 13.5 hours on three different occasions
      at two day intervals. Animals were then divided into three groups, receiving one
      of the three diets for 42 days. Dietary preference was tested again. Hepatic and
      muscle glucose and fatty acid utilization were measured in vitro and body
      composition was determined. Most of the rats preferred the mimetic diet over
      either control or high-fat diet, but there was no correlation between preference
      for a diet and intake of that diet during the experimental period. Animals fed
      either the high-fat or mimetic diet had greater energy intakes and body fat
      contents than control rats. Stepwise multiple regression determined which
      combination of variables correlated with energy intake of animals in each group.
      In rats fed high-fat diet, energy intake = 7.2 hepatic fatty acid oxidation (FAO)
      -0.2 hepatic glycogen - 131 muscle glycogen -0.9 hepatic fatty acid
      esterification (FAE) + 1.3 hepatic fatty acid synthesis (FAS) (R2 = 0.67). In
      rats fed mimetic diet, energy intake = 77.3 initial weight + 4.5 hepatic FAS -2.4
      serum free fatty acids + 68.4 serum insulin (R2 = 0.67). These data suggest that
      obesity can be induced by changing the orosensory properties of a diet without
      changing macronutrient composition.

PMID- 7812416
TI  - Comparison of body fat estimates derived from underwater weight and total body
      water.
AB  - The purpose of this study was to compare the techniques of underwater weighing
      and analysis of total body water for estimating body fat with that derived from a
      3-compartment model combining total body density and total body water. Body fat
      was estimated from: (1) body density using the Siri equation; (2) total body
      water assuming a hydration factor of 0.73 for fat free mass; and (3) the 3
      compartment model combining body density and body water. The criterion method in
      this study was body fat mass determined from Siri's 3-compartment model. The
      subjects in this study included 10 obese men (41 +/- 10 years; 115.5 +/- 16.6
      kg), 7 elderly men (68 +/- 6 years, 77.1 +/- 7.4 kg), and 18 young men (24 +/- 5
      years; 71.0 +/- 9.2 kg). Body density was obtained by underwater weight with
      simultaneous determination of lung volume by helium dilution. Body water was
      obtained from zero-time extrapolation of isotope washout over 10-14 days
      following an oral dose of 2H2O and H2(18)O. Estimates of body fat derived from
      total body water were significantly higher than that derived from underwater
      weight in the elderly (1.4 +/- 1.5 kg; P < 0.05) and younger (3.0 +/- 2.8 kg; P <
      0.001) men. In the obese subjects, there was no significant difference in body
      fat estimates between the two techniques (mean difference = 1.3 +/- 5.1 kg). The
      overestimation of body fat from total body water relative to underwater weight
      was negatively associated with body fat mass estimated from the 3-compartment
      model combining measurement of density and water (r = -0.35; P = 0.04). It is
      concluded that total body water overestimates body fat relative to underwater
      weight, and that this effect is more pronounced in leaner subjects.

PMID- 7812420
TI  - Effects of weight reduction programs on close family members.
AB  - Ninety-two patients in long-term treatment for obesity completed a questionnaire
      on the weight development of their close family members. Of 47 such relatives, 37
      had lost a mean of 6.1 kg and 10 increased a mean of 5.1 kg. Treatment of obesity
      will affect many more than those taking part in the actual program and generally
      result in weight loss. This effect on family members was mostly considered
      beneficial.

PMID- 7812421
TI  - Major depression during dexfenfluramine treatment.

PMID- 7812422
TI  - Virtual reality in medicine.

PMID- 7812423
TI  - Emerging medical applications of virtual reality: a surgeon's perspective.
AB  - Medical applications for virtual reality (VR) technologies are just beginning to
      emerge. These include VR surgical simulators, telepresence surgery, complex
      medical database visualization, and rehabilitation. These applications are
      mediated through the computer interface and embody VR as an integral part of a
      paradigm shift in the field of medicine. The Green Telepresence Surgery System
      consists of two components, the surgical workstation and the remote worksite. At
      the remote site there is a 3-D camera system and responsive manipulators with
      sensory input. At the workstation there is a 3-D monitor and dexterous handles
      with force feedback. The VR surgical simulator is a stylized recreation of the
      human abdomen with several essential organs. Using a head-mounted display and
      DataGlove, a person can learn anatomy from a new perspective by 'flying' inside
      and around the organs, or can practice surgical procedures with a scalpel and
      clamps. Database visualization creates 3-D images of complex medical data for new
      perspectives in analysis. VR applications in rehabilitation medicine permit
      impaired individuals to perform tasks not otherwise available to them, allow
      accurate assessment and therapy for their disabilities, and help architects
      understand their critical needs in public or personal space. And to support these
      advanced technologies, the operating room and hospital of the future will be
      first designed and tested in virtual reality, bringing together the full power of
      the digital physician.

PMID- 7812424
TI  - Augmenting reality in rehabilitation medicine.
AB  - Virtual reality comprises the computer-based generation of realistic three
      dimensional visual, auditory, and tactile environments in which a user can
      explore and interact with virtual objects. Although traditionally used for input
      devices to virtual worlds, the instrumented glove and sensor technologies of
      virtual reality may provide a dramatic new method for the measurement and
      amplification of human motion. This paper discusses some potential uses of
      virtual reality technology to support and augment routine activities for people
      who have physical disabilities. We present two different but related applications
      of this technology.

PMID- 7812425
TI  - Methods in the Virtual Wetlab I: rule-based reasoning driven by nearest-neighbor
      lattice dynamics.
AB  - We describe a discrete dynamical systems approach to exploring the hypothesis
      trees associated with wetlab experiments. On-going applications of the method to
      experimental research using a genetically engineered mouse animal model with
      severe combined immune deficiency (SCID) in the area of HIV infection are
      outlined as an example. In conclusion, we survey how this method can be used to
      engineer an informational murine, called Cybermouse [Mus Cyberspacea], that can
      be experimented upon using current immersion technologies.

PMID- 7812426
TI  - Dynamic force feedback in a virtual knee palpation.
AB  - A virtual model of a knee joint with muscles, ligaments and bones has been
      developed. This model includes realistic 3-D surface deformation and tissue
      stiffnesses. Tissue and bone deformation (palpation) produces real time force
      feedback to the user hand wearing a DataGlove and Rutgers Master. Collision
      detection algorithms determine when and where the virtual hand palpates the
      surface model. This user interaction with the muscles and bones of a human knee
      model may be used as a training and planning tool for knee surgery.

PMID- 7812427
TI  - A resource guide to VR in medicine.
AB  - This guide provides a bibliography of many of the most noteworthy contributions
      to the emerging literature about virtual reality in medicine, along with listings
      of the most relevant conferences and resources for researchers. This is an
      abridged version of a continuously updated comprehensive document which is
      available on-line to the research community.

PMID- 7812428
TI  - Changes, changes, changes: what's a nurse to do?

PMID- 7812429
TI  - 'Point of care' systems: the organization of nursing information.

PMID- 7812430
TI  - Finding the facts on computer software.

PMID- 7812431
TI  - Attitude.

PMID- 7812432
TI  - Dealing with difficult people.

PMID- 7812433
TI  - Genomic mapping of Pseudomonas aeruginosa PAO.

PMID- 7812434
TI  - Conservation of gene arrangement and an unusual organization of rRNA genes in the
      linear chromosomes of the Lyme disease spirochaetes Borrelia burgdorferi, B.
      garinii and B. afzelii.
AB  - Physical maps of the chromosomes of the Lyme disease spirochaetes Borrelia
      garinii and Borrelia afzelii have been elucidated for the enzymes CspI, SgrAI, I
      CeuI, SmaI, EagI, BssHII, MluI and ApaI by two-dimensional pulsed-field gel
      electrophoresis techniques. The maps contain 42 sites for B. garinii and 32 for
      B. afzelii. The mapping studies showed that the two chromosomes are linear DNA
      molecules of 953 and 948 kbp, respectively. A comparison of the physical maps of
      B. garinii and B. afzelii and the published map of the other Lyme disease
      spirochaete, Borrelia burgdorferi [Davidson, B.E., MacDougall, J. & Saint Girons,
      I. (1992) J Bacteriol 174, 3766-3774] revealed that the three chromosomes have
      few endonuclease sites in common, apart from a cluster in rrl (encoding 23S rRNA)
      and rrs (encoding 16S rRNA). Cloned borrelial genes were used as specific
      hybridization probes to construct genetic maps, using the physical maps as a
      basis. The resulting maps contain 41 genetic loci for B. burgdorferi, 39 for B.
      garinii, and 33 for B. afzelii. In contrast to the physical maps, the three
      genetic maps are closely related, with no detectable differences in gene order
      along the entire length of the chromosome. It is concluded that the chromosomes
      of these three borrelial species have undergone no major rearrangements,
      deletions or insertions during their evolution from a common ancestor. Detailed
      mapping of the region of the B. garinii and B. afzelii chromosomes that encodes
      rRNA revealed that each chromosome contains one copy of rrs separated by 5 kbp
      from two copies each of rrl and rrf (encoding 5S rRNA). (ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7812435
TI  - Differential activity of Rickettsia rickettsii opmA and ompB promoter regions in
      a heterologous reporter gene system.
AB  - The outer membrane of the Gram-negative obligate intracellular parasite
      Rickettsia rickettsii contains two large surface protein antigens with
      approximate molecular masses of 200 and 135 kDa termed rOmpA and rOmpB,
      respectively. rOmpB is the most abundant protein in the outer membrane, while
      rOmpA is a relatively minor constituent. Densitometry of intrinsically
      radiolabelled protein profiles from R. rickettsii-infected Vero cells indicated a
      molar ratio of approximately 1:9 between rOmpA and rOmpB. The putative promoter
      5' untranslated regions (5' UTR) from their recently characterized genes (rompA
      and rompB) were placed in the promoter assay vector pKK232-8 to test whether
      these elements conserve aspects of differential expression in a heterologous host
      reporter system. Primer extension analysis of RNA from Escherichia coli clones
      containing the constructs indicated that E. coli RNA polymerase faithfully
      utilizes rompA and rompB transcription start sites identified previously in R.
      rickettsii. The rompB insert directs 28-fold higher levels of chloramphenicol
      acetyl transferase activity than the rompA insert.

PMID- 7812436
TI  - The effect of nutrient limitation on glycerol uptake and metabolism in continuous
      cultures of Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa NM48, a non-mucoid derivative of an alginate-producing
      strain isolated from a cystic fibrosis patient, was grown in batch culture with
      glycerol, glucose or succinate as carbon source, and in continuous culture (D
      0.05 h-1) under glycerol or glucose limitation. Glycerol uptake, glycerol kinase
      and glycerol-3-phosphate dehydrogenase were induced by glycerol, but not by
      glucose or succinate. Linear uptake of [14C]glycerol by washed cells (Km < or = 2
      microM) was inhibited by unlabelled glycerol and glyceraldehyde, but not by
      cyanide or the uncoupling agent carbonyl cyanide p
      trifluoromethoxyphenylhydrazone (FCCP), and was accompanied by substantial
      intracellular accumulation of glycerol-3-phosphate and/or dihydroxyacetone
      phosphate but not glycerol. Prolonged growth under glycerol limitation led to
      substantial increases in the activities and/or concentrations of the enzymes
      catalysing glycerol uptake and metabolism, together with a 48,000 M(r) outer
      membrane protein which was also over-expressed following prolonged growth under
      glucose limitation. The N-terminal amino acid sequence (AEAFSPN-) and
      electrophoretic properties of this protein were the same as those of the
      previously characterized glucose porin (OprB) from P. aeruginosa, indicating that
      this porin is active with both glucose and glycerol. It is concluded that during
      growth under glycerol limitation, glycerol is transported into P. aeruginosa NM48
      via OprB and a high-affinity, binding-protein-independent facilitated-diffusion
      system.

PMID- 7812438
TI  - Biodegradation of sulphosuccinate: direct desulphonation of a secondary
      sulphonate.
AB  - The bacterial biodegradation of a secondary sulphonate, sulphosuccinate, has been
      shown to occur by direct desulphonation. A bacterium, designated Pseudomonas sp.
      BS1, was isolated from activated sewage sludge, for its capacity to grow on
      sulphosuccinate as the sole source of carbon and energy. Cultures grown on
      sulphosuccinate were able to convert this substrate to sulphite which was
      subsequently oxidized rapidly to sulphate. The sequence of desulphonation and
      carbon-chain catabolism of sulphosuccinate was determined from measurements of
      the kinetics of sulphite and 14CO2 release from specifically radiolabelled
      sulpho[1,4-14C]succinate and sulpho[2,3-14C]succinate, which were synthesized
      from the corresponding maleic anhydrides. When each radiolabelled compound was
      incubated separately with washed-cell suspensions of Pseudomonas BS1, sulphite
      was released before 14CO2, as shown by chemical assay and radiorespirometry,
      respectively. Differences in the kinetics and extent of 14CO2 release from the
      1,4- and 2,3-labelled substrates were consistent with entry of the intact C4
      chain into the citric acid cycle. When carrier oxaloacetate was added to
      incubation mixtures containing resting-cell suspensions and radiolabelled
      sulphosuccinate, a radiolabelled metabolite with the same HPLC retention time as
      oxaloacetate accumulated. No radioactive metabolites accumulated when carrier
      oxaloacetate was replaced with succinate, fumarate or malate. Collectively, the
      data indicated co-production of sulphite and oxaloacetate from sulphosuccinate,
      which is interpreted in terms of an oxidative desulphonation mechanism.

PMID- 7812437
TI  - Regulation of transfer genes of promiscuous IncP alpha plasmid RK2: repression of
      Tra1 region transcription both by relaxosome proteins and by the Tra2 regulator
      TrbA.
AB  - The Tra1 region of broad host range IncP alpha plasmid RK2 encodes proteins
      essential for its promiscuous conjugative transfer and includes oriT, the site at
      which nicking occurs to initiate transfer replication. Unregulated expression of
      the Tra1 region genes would be likely to place a major burden on the host. To
      investigate the control of these genes the three transcriptional promoters from
      this region were cloned by PCR and inserted into xylE promoter probe vectors. The
      strength of traJp and traKp was estimated to be six to eightfold less than the
      strong trfA promoter which is required for expression of genes for vegetative
      replication of RK2. The traG promoter was about one-tenth the strength of the
      other two. These promoters are not repressed by products of the central control
      operon of RK2. However, traJp and traKp, which are arranged as back to back
      divergent promoters in the oriT region, are repressed by TraK which constitutes
      part of the relaxosome necessary for nicking at oriT. A second relaxosome
      protein, TraJ, represses traJp. traGp is not repressed by any relaxosome
      proteins. All three promoters are repressed by TrbA, which is encoded at the
      start of the trb operon containing the rest of the transfer genes (the Tra2
      region). These circuits provide: (i) an autoregulatory way of ensuring production
      of enough relaxosome proteins without overburdening the host; and (ii) a means of
      coordinating expression of both blocks of transfer genes.

PMID- 7812439
TI  - SDS-degrading bacteria attach to riverine sediment in response to the surfactant
      or its primary biodegradation product dodecan-1-ol.
AB  - A laboratory-scale river microcosm was used to investigate the effect of the
      anionic surfactant sodium dodecyl sulphate (SDS) on the attachment of five
      Pseudomonas strains to natural river-sediment surfaces. Three of the Pseudomonas
      strains were chosen for their known ability to express alkylsulphatase enzymes
      capable of hydrolysing SDS, and the other two for their lack of such enzymes. One
      strain from each category was isolated from the indigenous bacterial population
      present in the river sediment used; other isolates were from soil or sewage. The
      alkylsulphatase phenotypes were confirmed by gel zymography of cell extracts.
      Addition of SDS to mixed suspensions of river sediment with any one of the
      biodegradation-competent strains stimulated the attachment of bacteria to the
      sediment particles. In contrast, the attachment of biodegradation-incompetent
      strains was weak and, moreover, was unaffected by SDS. The SDS-stimulated
      attachment for competent organisms coincided with rapid biodegradation of the
      surfactant. The primary intermediate of SDS biodegradation, dodecan-1-ol,
      accumulated transiently, and the numbers of attached bacteria correlated closely
      with the amount of dodecan-1-ol present. Direct addition of dodecan-1-ol also
      stimulated attachment but the effect was more immediate compared with SDS, when
      there was a lag period of approximately 2 h. To account for these observations, a
      model is proposed in which SDS stimulates the attachment of biodegradation
      competent bacteria through its conversion to dodecan-1-ol, and it is hypothesized
      that the observed reversibility of the attachment is due to the subsequent
      removal of dodecan-1-ol by further bacterial metabolism.

PMID- 7812440
TI  - Gellan lyases--novel polysaccharide lyases.
AB  - A number of bacterial strains capable of degrading the bacterial
      exopolysaccharide gellan have been isolated by standard enrichment procedures.
      They include several pink-pigmented Gram-negative rod-shaped bacteria. A red
      pigmented Gram-positive bacillus earlier found to degrade the exopolysaccharide
      xanthan from Xanthomonas campestris also showed slight gellanase activity. All
      the Gram-negative bacteria are non-fermentative, motile and amylase-producing.
      The gellan degradation in each case is due to eliminase-type enzymes (lyases)
      which appear to be extracellular enzymes cleaving the sequence... beta-D-glucosyl
      (1-->4)-beta-D-glucuronosyl... in the tetrasaccharide repeat unit of the
      substrate polysaccharides. Although in some isolates these enzymes appear to be
      exo-acting, it appears from the loss in viscosity of the alternative substrate
      deacetylated rhamsan that they are predominantly endoenzymes. The enzyme activity
      is inducible: it is almost absent from glucose-grown cells. Associated with the
      'gellanase' activity, all the Gram-negative bacterial isolates possess
      intracellular alpha-L-rhamnosidase and beta-D-glucosidase activities apparently
      located in the periplasm. The enzymes are highly specific and fail to cause
      significant degradation of most of the other bacterial exopolysaccharides which
      have been shown to be structurally related to gellan. As well as acting on
      gellan, they exert similar degradative activity against the chemically deacylated
      form of polysaccharide S194 (rhamsan gum), which is effectively a
      gentiobiosylated form of gellan. The enzymes only have relatively slight activity
      against the natural, acylated gellan-like polysaccharides from the bacteria now
      designated as strains of Sphingomonas paucimobilis.

PMID- 7812441
TI  - Use of a series of chemostat cultures to isolate 'improved' variants of the Quorn
      mycoprotein fungus, Fusarium graminearum A3/5.
AB  - Variants (designated A23-S and A24-S) of the Quorn myco-protein fungus, Fusarium
      graminearum A3/5 were isolated from a series of glucose-limited cultures grown at
      a dilution rate of 0.18 h-1 for a combined total of 109 d. These variants had
      unchanged mycelial morphologies but, when grown in mixed culture with the
      parental strain (A3/5) in glucose-limited chemostat culture at 0.18 h-1, A23-S
      and A24-S had selection coefficients of 0.013 and 0.017 h-1, respectively, and
      supplanted A3/5. When a monoculture of A23-S was grown in a glucose-limited
      culture at a dilution rate of 0.18 h-1, the appearance of highly branched (so
      called colonial) mutants was delayed compared with their appearance in chemostat
      cultures of the parental strain. Furthermore, when a monoculture of A24-S was
      grown in glucose-limited culture at 0.18 h-1, the appearance of colonial mutants
      was delayed even further. Thus, it is possible to isolate advantageous (relative
      to A3/5) variants of F. graminearum A3/5 which have unchanged mycelial
      morphologies, but in which the appearance of colonial mutants is delayed.

PMID- 7812442
TI  - Evolution of Fusarium graminearum A3/5 grown in a glucose-limited chemostat
      culture at a slow dilution rate.
AB  - The evolution of Fusarium graminearum A3/5 grown in a glucose-limited chemostat
      at a dilution rate of 0.05 h-1 (doubling time of 13.9 h) was followed for 957 h
      or 69 generations. Periodic selection of advantageous mutants was monitored in
      the culture by determining increases and decreases in the concentration of
      cycloheximide-resistant macroconidia in the population. Six peaks in the
      concentration of cycloheximide-resistant macroconidia were observed representing
      five adaptive changes in the population; on average, an adaptive change occurred
      once every 148 +/- 22 h (mean +/- SE). The selection coefficient of strains
      present at the start of each increase in the concentration of cycloheximide
      resistant macroconidia (i.e. after the establishment of a new advantageous
      strain) was determined relative to A3/5 and was found to increase progressively
      with time. When grown at a dilution rate of 0.05 h-1, the strain (A28-S) isolated
      from the last adaptive peak had a selection coefficient of 0.023 h-1 relative to
      A3/5, but A28-S lost its selective advantage when grown at a dilution rate of
      about 0.11 h-1 and was at a selective disadvantage when grown at a dilution rate
      higher than 0.11 h-1. The Km value (12 +/- 5 microM) for uptake of glucose by A28
      S was significantly lower than that for A3/5. The spontaneous mutation rate from
      cycloheximide sensitivity to cycloheximide resistance was estimated to be 1.8 (+/
      0.2) x 10(-6) h-1 or 2.5 x 10(-5) generation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7812443
TI  - Induction of major heat-shock proteins of Saccharomyces cerevisiae, including
      plasma membrane Hsp30, by ethanol levels above a critical threshold.
AB  - Many of the changes induced in yeast by sublethal yet stressful amounts of
      ethanol are the same as those resulting from sublethal heat stress. They include
      an inhibition of fermentation, increased induction of petites and stimulation of
      plasma membrane ATPase activity. Ethanol, at concentrations (4-10%, v/v) that
      affect growth and fermentation rates, is also a potent inducer of heat-shock
      proteins including those members of the Hsp70 protein family induced by heat
      shock. This induction occurs above a threshold level of about 4% ethanol,
      although different heat-shock proteins and heat-shock gene promoters are
      optimally induced at different higher ethanol levels. In addition ethanol (6-8%)
      causes the same two major changes to integral plasma-membrane protein composition
      that result from a sublethal heat stress, reduction in levels of the plasma
      membrane ATPase protein and acquisition of the plasma membrane heat-shock protein
      Hsp30.

PMID- 7812444
TI  - Involvement of mitochondria in the assimilatory metabolism of anaerobic
      Saccharomyces cerevisiae cultures.
AB  - The possible physiological role of mitochondria in anaerobically grown
      Saccharomyces cerevisiae was investigated via enzyme localization and inhibitor
      studies. Almost all of the activity of citrate synthase (EC 4.1.3.7) was
      recovered in the mitochondrial fraction after differential centrifugation of
      spheroplast lysates. The enzyme exhibited a high degree of latency which was
      demonstrated by sonication of the mitochondrial fractions. Since citrate synthase
      is an important enzyme in anabolic reactions, a consequence of this localization
      is the requirement for transport of metabolites across the mitochondrial
      membranes. Such transport is likely to require energy which, as a result of
      anaerobiosis, cannot be supplied by respiration. It was therefore investigated
      whether ATP translocation into the mitochondria by an ADP/ATP translocase might
      be involved in anaerobic mitochondrial energy metabolism. It was shown that
      addition of the ADP/ATP translocase inhibitor bongkrekic acid to anaerobic
      cultures indeed inhibited growth, although only partially. It is concluded that
      mitochondria of S. cerevisiae fulfil a vital role in anaerobic sugar metabolism.

PMID- 7812445
TI  - Ca(2+)-ATPase-driven calcium accumulation in Ustilago maydis plasma membrane
      vesicles.
AB  - Ca2+ transport has been measured across plasma membrane vesicles isolated from
      cells of Ustilago maydis. This transport was found to be ATP- (or to a lesser
      extent GTP) and Mg(2+)-dependent. Inconsistent release of Ca2+ from intact
      vesicles was obtained using the calcium ionophore A23187. However, Ca2+ was
      released by Triton X-100 in a concentration-dependent manner. Transport was
      inhibited by vanadate (> 50%) and erythrosin B (about 50%), I50 being about 10
      microM for both inhibitors. In the presence of the protonophores CCCP or
      gramicidin, partial inhibition of Ca2+ transport (about 20%) was observed, but
      the Ca(2+)-channel blockers, nifedipine, diltiazem and verapamil had no effect,
      although the latter inhibited proton transport. The results indicate that Ca2+
      transport in U. maydis is regulated by a P-type ATPase with similar properties to
      that found in higher plants.

PMID- 7812446
TI  - Mosaic structure of large regions of the Lactococcus lactis subsp. cremoris
      chromosome.
AB  - Lactococcus lactis subsp. lactis and Lactococcus lactis subsp. cremoris are
      closely related phenotypically and genetically. Here we report that certain
      regions of their chromosomes diverge considerably more than others. Conserved
      regions differ by less than 20%, whilst variable regions differ by more than 60%.
      This mosaic structure may have arisen by horizontal gene transfer from distantly
      related bacteria since in a particular region of the L. lactis subsp. cremoris
      chromosome the G+C content and the codon bias are not typical for lactococci.
      Such an exchange, which conserves the function of the gene and cannot be achieved
      under selective pressure, may be of considerable importance in the evolution of
      bacteria.

PMID- 7812447
TI  - Sequence and organization of the lactococcal prolate-headed bIL67 phage genome.
AB  - bIL67 is a broad-host-range prolate-headed phage that is active against
      Lactococcus cells. The complete phage genome sequence of 22195 bp was
      established. Thirty-seven open reading frames (ORFs) organized in two clusters
      were identified. Functions were assigned to the putative products of six of the
      ORFs on the basis of comparison of the deduced amino acid sequences to known
      proteins, analysis of structural features of the proteins and search for
      conserved motifs. These were a DNA polymerase, a protein involved in
      recombination, a lysin, a terminase subunit, a structural protein and a holin.

PMID- 7812448
TI  - Analysis of the expression and regulation of the gerB spore germination operon of
      Bacillus subtilis 168.
AB  - The gerB spore germination operon of Bacillus subtilis 168 is a homologue of the
      gerA spore germination operon. The expression and regulation of the gerB operon
      has been examined using a lacZ transcriptional fusion and the transcriptional
      start defined. The gerB operon is expressed during sporulation under the control
      of RNA polymerase containing the forespore-specific sigma factor, delta G. This
      is a further homology to the gerA operon, which is similarly regulated. It is
      predicted from the localization of expression and the encoded primary sequences
      that the GerB proteins are located at the inner spore membrane.

PMID- 7812449
TI  - Malate synthase from Corynebacterium glutamicum: sequence analysis of the gene
      and biochemical characterization of the enzyme.
AB  - Malate synthase is one of the key enzymes of the glyoxylate cycle and is
      essential for growth on acetate as sole carbon source. The aceB gene from
      Corynebacterium glutamicum, encoding malate synthase, was isolated, subcloned and
      expressed in Escherichia coli and C. glutamicum. Sequencing of a 3024 bp DNA
      fragment containing the aceB gene revealed that it is located close to the
      isocitrate lyase gene aceA. The two genes are separated by 597 bp and are
      transcribed in divergent directions. The predicted aceB gene product consists of
      739 amino acids with an M(r) of 82,362. Interestingly, this polypeptide shows
      only weak identity with malate synthase polypeptides from other organisms and
      possesses an extra N-terminal sequence of about 170 amino acid residues.
      Inactivation of the chromosomal aceB gene led to the absence of malate synthase
      activity and to the inability to grow on acetate, suggesting that only one malate
      synthase is present in C. glutamicum. The malate synthase was purified from an
      aceB-overexpressing C. glutamicum strain and biochemically characterized. The
      native enzyme was shown to be a monomer migrating at an M(r) of about 80,000. By
      sequencing the N-terminus of malate synthase the predicted translational start
      site of the enzyme was confirmed. The enzyme displayed Km values of 30 microM and
      12 microM for the substrates glyoxylate and acetyl CoA, respectively. Oxalate,
      glycolate and ATP were found to be inhibitors of malate synthase activity. The
      present study provides evidence that the malate synthase from C. glutamicum is
      functionally similar to other malate synthase enzymes but is different both in
      size and primary structure.

PMID- 7812450
TI  - Cloning and nucleotide sequence of the carboxynorspermidine decarboxylase gene
      from Vibrio alginolyticus.
AB  - The gene (nspC) encoding carboxynorspermidine decarboxylase (CANS DC), the last
      enzyme in norspermidine biosynthesis, in Vibrio alginolyticus was isolated by
      immuno-screening and its complete nucleotide sequence was determined. Sequence
      analysis of the subcloned fragment (2.0 kb) revealed an ORF of 1131 bp encoding a
      protein of 377 amino acids with a calculated molecular mass of 42,008 Da. The
      sequence of 20 N-terminal amino acids of purified CANS DC was found to be
      identical to that predicted from the nspC gene. A putative ribosome binding
      sequence was observed 8 bp upstream from the translation start site (ATG), and
      promoter- and terminator-like sequences were detected upstream and downstream of
      the ORF, respectively. Database searches identified no similar proteins, but the
      deduced amino acid sequence contained a putative pyridoxal 5'-phosphate binding
      region similar to those of the bacterial meso-2,6-diaminopimelate decarboxylases
      and eukaryotic ornithine decarboxylases. Another full ORF was found on the
      opposite strand downstream from the nspC gene. It encoded a protein of 69 amino
      acids with a calculated molecular mass of 7441 Da, which exhibited some weak
      similarity to ScrR, a repressor protein of V. alginolyticus, in the helix-turn
      helix DNA binding domain, but did not appear to be expressed in the host cells.

PMID- 7812452
TI  - Glycine betaine transport by Staphylococcus aureus: evidence for feedback
      regulation of the activity of the two transport systems.
AB  - The regulation of glycine betaine accumulation by Staphylococcus aureus was
      investigated. The accumulation of glycine betaine was regulated by the osmotic
      pressure of the medium and the low affinity transport system played the major
      role in this regulation. Mutants were isolated that lack the low affinity,
      osmotically activated glycine betaine/proline transport system. Such mutants
      accumulated glycine betaine via the high affinity system but the glycine betaine
      pool was smaller and responded poorly to osmotic pressure changes. The regulation
      of glycine betaine transport has revealed that at the steady state net influx is
      reduced and that this is achieved by inhibition of both the low affinity and the
      high affinity transport systems. Cells pre-loaded with glycine betaine exhibited
      a reduced Vmax for both systems: the low affinity system was reduced in activity
      fivefold and the high affinity system was reduced 10-fold and became virtually
      undetectable. Although glycine betaine transport at the steady state is reduced,
      retention of the compatible solute is an active process since addition of an
      uncoupler provokes rapid release of the accumulated material. These data suggest
      that feedback regulation of the activity of the uptake systems is a major
      mechanism for controlling the level of compatible solute accumulation.

PMID- 7812451
TI  - Growth temperature regulates the induction of beta-lactamase in Pseudomonas
      fluorescens through modulation of the outer membrane permeation of a beta-lactam
      inducing antibiotic.
AB  - The psychrotrophic bacterium, Pseudomonas fluorescens strain MFO, is more
      sensitive to the beta-lactam mezlocillin at a low growth temperature (i.e. 8
      degrees C) than at a higher growth temperature (28 degrees C). An early effect of
      this antibiotic at all temperatures is bacterial filamentation, but this occurs
      later at 8 degrees C than at 28 degrees C, which suggests a lower permeability of
      the cell envelopes to mezlocillin at low growth temperature. beta-Lactamase
      production is later induced by mezlocillin, but the level of this induction also
      depends on the growth temperature, the overall induction being much less
      efficient at 8 degrees C. It is hypothesized that the periplasmic concentration
      of the drug might be too low at 8 degrees C to allow efficient beta-lactamase
      induction; this hypothesis was confirmed by the demonstration that beta-lactamase
      production is drastically enhanced in cells cultivated at 8 degrees C
      permeabilized for 10 min by Na-EDTA. In addition, induction kinetic curves
      display a marked dependence upon growth temperature. A rapid saturation was
      evident when mezlocillin concentrations were increased at 8 degrees C; this was
      not seen at 28 degrees C at up to 1000 micrograms mezlocillin ml-1. The results
      are discussed in terms of two different routes of drug permeation, depending on
      the growth temperature.

PMID- 7812453
TI  - Evidence for feedback (trans) regulation of, and two systems for, glycine betaine
      transport by Staphylococcus aureus.
AB  - Previous reports are in conflict as to the number of transport systems for
      glycine betaine in Staphylococcus aureus. Cells grown in complex medium exhibited
      a single transport system of moderate affinity. Cells grown in defined medium in
      the absence of glycine betaine showed a high affinity and a low affinity
      transport system. Cells grown in the presence of glycine betaine in the presence
      of osmotic stress in either complex or defined media accumulated large pools of
      internal glycine betaine. Smaller, but still significant, amounts of glycine
      betaine were accumulated by cells grown in its presence in either complex or
      defined media in the absence of osmotic stress. Cells grown in defined medium in
      the presence of glycine betaine in the presence or absence of osmotic stress
      showed lower rates of glycine betaine transport than cells grown in its absence.
      This suggests that glycine betaine transport is subject to feedback or trans
      inhibition by internal glycine betaine. This can explain the difference in
      observed kinetics in cells grown in complex or defined media, the high affinity
      system being predominantly inhibited in cells grown in complex medium.

PMID- 7812454
TI  - Is the solubilized product from the degradation of lignocellulose by
      actinomycetes a precursor of humic substances?
AB  - Three actinomycetes (Streptomyces sp. EC22, Streptomyces viridosporus T7A and
      Thermomonospora fusca BD25) were assessed for their ability to degrade ball
      milled wheat straw. All gave maximum levels of solubilized lignocellulose
      products (APPL) at the beginning of the stationary phase of growth (72-96 h). Low
      molecular-mass aromatic compounds extracted from the APPL were analysed by
      reverse-phase and gas chromatography. Although the number of chromatographic
      peaks detected made identification of the products difficult, p-coumaric acid (4
      hydroxycinnamic acid), protocatechuic acid (3,4-dihydroxybenzoic acid), gallic
      acid (3,4,5-trihydroxybenzoic acid), gallic acid methyl ester (methyl-3,4,5
      trihydroxybenzoate) and 4-methoxyphenol were recognized. The infrared spectra of
      the three strains were similar to the spectra of humic acids, with all APPL
      extracts showing carbonyl, amino, carboxyl, aliphatic and aromatic group
      vibrations. Also detected were peptide linkages of proteins. The results suggest
      a role for actinomycetes in the formation of humic substances in soils and
      composts.

PMID- 7812455
TI  - Partial characterization of specific inducers of a cuticle-degrading protease
      from the insect pathogenic fungus Metarhizium anisopliae.
AB  - The insect pathogenic fungus Metarhizium anisopliae produces several
      extracellular cuticle-degrading proteases and evidence is consistent with one of
      these, PR1, which is a chymoelastase, being a determinant of pathogenicity. We
      have shown previously that PR1 production is regulated by both carbon catabolite
      and nitrogen metabolite repression and also by specific induction under
      derepressed conditions by insect cuticle. In the present work we have established
      that an enzymically released proteinaceous component(s) of insect cuticle is
      capable of inducing PR1 (based on appearance of extracellular activity). Cuticle
      of the desert locust Schistocerca gregaria treated with KOH to remove protein
      failed to induce PR1 production, whereas cuticle treated with either chloroform
      or ether to remove lipids still induced PR1. Cuticle digested with either PR1 or
      the trypsin-like PR2 of M. anisopliae released peptides mainly in the range 150
      2000 Da; addition of these peptides generated by PR1 or PR2 at 3 micrograms
      alanine equivalents ml-1 induced PR1 production to a level similar (75%) to that
      obtained with untreated insect cuticle. Several amino acids and peptides which
      are abundant in insect cuticular protein (Ala, Gly, Ala-Ala, Ala-Ala-Ala, Ala-Pro
      and Pro-Ala) were tested at a range of concentrations and in restricted cultures
      for their ability to induce PR1. None induced the protease to the levels seen
      with cuticle or peptides enzymically released from cuticle, although some dimers
      and notably the monomers Ala and Gly gave 2-2.7-fold enhanced PR1 activity above
      depressed basal levels (up to 48-57% of that achieved with induced synthesis on
      cuticle).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7812456
TI  - Endogenous ADP-ribosylation during development of the prokaryote Myxococcus
      xanthus.
AB  - We examined endogenous ADP-ribosylation of proteins during the development of the
      prokaryote Myxococcus xanthus. In vivo and in vitro endogenous ADP-ribosylation
      of M. xanthus proteins was detected and the profile of modified proteins changed
      during development. Adenosine and nicotinamide inhibited ADP-ribosylation.
      Nicotinamide stimulated cells at low density to develop, in a manner similar to
      that previously observed with adenosine. Higher concentrations of nicotinamide
      inhibited aggregation. The in vivo effects of nicotinamide on developing M.
      xanthus cells correlate with its in vitro effects on ADP-ribosylation and the
      developmental profile of putative ADP-ribosylation substrates. These results
      suggest that ADP-ribosylation may regulate developmental proteins in M. xanthus.

PMID- 7812458
TI  - [Natural history of human transmissible subacute spongiform encephalopathies].
AB  - Transmissible spongiform subacute encephalopathies are rare fatal diseases which
      comprise in humans Creutzfeldt-Jakob disease (CJD), Kuru, Gerstmann Straussler
      Scheinker, and Fatal Familial Insomnia (FFI). Their etiologic agents (Prions or
      TSA, for transmissible spongiform encephalopathy agents) are still unknown.
      TSA/prions resist all the physico-chemical procedures which are efficient against
      the other micro-organisms. These diseases are characterised by a long incubation
      period which may be as long as 40 years. Clinically, symptoms are only
      neurological, without any sign of immune response either in blood or
      cerebrospinal fluid. Neuropothalogy includes neuronal vacuolisation, neuronal
      death, spongiosis, gliosis with hyperastrocytosis. The biochemical hallmark is
      the post-translational accumulation of a host-encoded protein, the prion protein
      (PrP). In infected individuals, PrP accumulates under a proteinase K resistant
      isoform (PrP-res) which amino acid sequence does not differ from the normal
      isoform (PrP-c) PrP gene (PRNP) is located on chromosome 20 in humans, and is the
      major determinant of the susceptibility to TSA/prions. Several hypotheses have
      been raised to explain the uncommon biologic properties of these agents. The
      prion hypothesis postulates that the agent is only composed of proteins, mainly
      the PrP-res. Others support the presence of a host independent genetic
      information of which PrP could be the virulence factor.

PMID- 7812457
TI  - Characterization of a 38 kDa penicillin-binding protein and its possible
      involvement in maintaining stationary-phase cells of Shigella dysenteriae.
AB  - This paper reports the first attempt to characterize the penicillin-binding
      proteins (PBPs) of Shigella dysenteriae, an important human pathogen. The PBP
      pattern of the membranes of S. dysenteriae closely resembles that of Escherichia
      coli membranes. A 38 kDa PBP which is an important target for the penem SCH34343,
      the cephamycin cefoxitin and the oxacephem moxalactam, has been purified. This
      PBP is immunologically related to a PBP of similar molecular mass in E. coli and
      is present at high levels in stationary-phase cells of S. dysenteriae.

PMID- 7812460
TI  - [Epidemiology of human diseases caused by unconventional transmissible agents].
AB  - Human unconventional viruses infections are scarcely found with a worldwide
      occurrence below 1/million inhabitants. The disease would be induced by an
      interaction between the patient's genetic characteristics and environmental
      factors. No link has been found between the occurrence of the disease in man and
      the presence of the animal form of the disease, i.e. scrapie. The professional
      risk has been pointed out for people working with animals or in the medical
      sector. Most iatrogenic cases are subsequent to a growth hormone treatment. The
      other cases are associated with different medical and surgical acts. But the
      transmission by blood transfusion remains questionable and must be clearly
      demonstrated.

PMID- 7812459
TI  - [Iatrogenic Creutzfeldt-Jakob disease. Lessons from cases secondary to extracted
      growth hormone in France].
AB  - Thirty cases of Creutzfeldt-Jakob disease (CJD) after cadaveric growth hormone
      treatment have been counted by the National Reference Center for iatrogenic CJD.
      The clinic presentation is homogeneous, beginning by neurological troubles
      (diplopia, unsteady gait) evolving rapidly in few months towards a severe
      neurological deterioration, insanity and death. All patients were treated between
      January 1984 and July 1985. The risk to transmit CJD with treatments of human
      origin (pituitary derived treatment, blood, placentas and corneal and dura mater
      graft) is analyzed. The selection of donors and techniques of purification on the
      one hand, the rigor of the indication and the quality of the followup on the
      other hand, are the only guarantees to reduce the risks secondary to utilization
      of products of human origin.

PMID- 7812461
TI  - [Molecular basis of familial and sporadic forms of human prion diseases].
AB  - Prion diseases, also known as transmissible subacute spongiform encephalopathies
      (TSSE), are rare neurodegenerative disorders of both humans and animals. Their
      biochemical hallmark is an accumulation in the brain of an abnormal form of the
      host-encoded prion protein (PrP). This pathological accumulation could result
      from a protein conformational change under the influence of unknown factors. The
      normal function of PrP is unknown. The abnormal form is thought to induce
      neurodegeneration when experimentally or accidentally introduced in recipient
      hosts. Such a possibility would explain the transmissible character of these
      diseases illustrated in humans by iatrogenic contamination. Considerable
      attention has been focused on the host PrP gene and its relation with the genetic
      susceptibility of humans and animals. Mutations in PRNP, the gene which encodes
      PrP in humans, are present in 17% of the patients and might be causative. In
      patients without any PRNP mutation, a coding polymorphism (129 Met/Val) defines a
      predisposing factor. Since few years, important progress in the molecular
      genetics of TSSE in both humans and animals have been performed and point out
      that the development of different forms of these diseases, experimental,
      iatrogenic or spontaneous, are strongly dependent on the primary structure of the
      host PrP.

PMID- 7812462
TI  - [Animal models of transmissible subacute spongiform encephalopathies].
AB  - The lack of suitable in vitro test explains the major importance of animal models
      in the study of Transmissible Spongiform Encephalopathies (TSE). Models using big
      animals are closer to natural situations, while solely rodent adapted models can
      be used currently in laboratories. Different scientific approaches based on the
      utilization of these models permitted to evidence the multifactorial character of
      TSE, with factors linked to the host and others linked to the TSE agents, also
      called prions. Prion protein (PrP) is the major host factor as it has been
      recently demonstrated by transgenetic studies. Among agent related factors, the
      notion of independant strains of TSE agents is now well established in inbred
      mice even if molecular studies have hitherto not been able to precise their exact
      nature. Although these models constitute powerful tools for the study of TSE, it
      has to be reminded that they can be far from natural situations.

PMID- 7812463
TI  - [Transmissible animal spongiform encephalopathies. Epidemiologic aspects].
AB  - This article presents an update of data about the transmissible spongiform
      encephalopathies which affect some animal species, particularly bovine spongiform
      encephalopathy in Great britain and in other countries where this disease is
      sporadic. The genetic susceptibility of scrapie in sheep and the natural
      transmission of these spongiform encephalopathies are discussed. The control
      measures for public health and animal health are presented.

PMID- 7812464
TI  - [Transfusion risks: importance of blood surveillance].
AB  - Transfusion risks result from the transfusion chain complexity and are due to
      human errors and limits of screening technics. Causes, mechanisms and
      manifestations of the main risks are mostly well known. Transfusion risks can be
      related to the donor, the blood donation or the transfusion act. The mechanisms
      are immediate or delayed. Environment can be a favorable factor. In France, rates
      of transfusion risks and the part of risk attributable to the environment are not
      known with accuracy because of the absence of a mandatory reporting system. The
      assessment of the existing prevention policies, essential for envisaging new
      actions, lacks rigour. The setting of means assessment and follow-up of
      transfusion safety as it was mentioned by the Comity of transfusion safety follow
      up (L. Degos, A. Goudeau, R. Salamon) in november 1991, and in the law no. 93-5
      of january 4, 1993 would allow the improvement of epidemiologic features of blood
      donation, blood use and transfusion risks.

PMID- 7812465
TI  - [Failure mechanisms in the transfusion process. Importance of anticipatory
      operational safety analysis].
AB  - The methods used for the safety previsional analysis of operations represent an
      interesting set of tools to follow the so-called transfusion process, defined as
      all the steps from donors sensitization to recipients follow-up. FMECA (Failure
      Mode Effects and Criticality Analysis) can be used as a prevention tool,
      independently of any dysfunction in the process. Of course, it can also be used
      following a failure, in order to analyse its causes and to apply specific
      corrections. Operation safety, quality insurance, epidemiologic surveillance and
      safety monitoring act in synergy. These three aspects of transfusion safety
      constitute a dynamic system.

PMID- 7812466
TI  - [Anti-HIV antibody screening kits and the difficulties of serology. Retrovirus
      Working Group of the Societe Francaise de la Transfusion Sanguine].
AB  - The combined HIV1 + HIV2 assays allow to screen simultaneously the subjects
      infected by HIV1 or by HIV2 (About 80 HIV1 for 1 HIV2 in blood donations in
      France). An improvement of both sensitivity and specificity was obtained by using
      artificial proteins which have been selected for having the most immuno-dominant
      epitopes. The sensitivity is defined by the study of samples from recent and very
      recent seroconverters and the specificity by testing 2000 unselected blood
      donors. All the early seroconversions must be recognized as positive and less
      than 0.5% false positive results must be found in blood donors. HIV1 variants,
      temporarily named sub-type O have brought a new difficulty to the HIV serology,
      due to a weak homology, especially in "env" domains, between these variants and
      the reference HIV1 strains. Subjects living in France and infected by this HIV1
      variant seem rare and the screening assays which miss some of these infected
      individuals seem capable to modify their reagents in order to recognize all of
      them.

PMID- 7812467
TI  - Health care system reform and public health. Protecting the safety net.
AB  - The most difficult to reach underserved populations are not likely to disappear
      even with universal insurance coverage. Universal coverage does offer all
      educated and motivated individuals, including those lacking financial resources,
      the opportunity to seek improved health through prevention services and treatment
      for illness. But, it would not guarantee that uneducated and unmotivated people,
      substance abusers, the chronically mentally ill, people with geographic or
      cultural barriers to access, or other traditionally underserved populations will
      use or be able to use a new system more wisely. These last groups, who, for
      various reasons, may underuse prevention services or delay contact until disease
      is transmitted or illness is advanced, will continue to add costs to a reformed
      health care system. Care must therefore be exercised in health care system reform
      to provide incentives for private-sector outreach to these problem populations.
      Even with incentives, however, history suggests that the private sector will
      either avoid or have difficulty incorporating the large groups of disadvantaged
      patients who in the past have relied on public health services and public
      hospitals for their health care. The public health sector will need to maintain
      the capacity to provide for the health care of many disadvantaged groups with
      historically poor access. It becomes critical in the budgetary trade-offs
      inherent in health care system reform that the infrastructure of the public
      health system not be damaged.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7812468
TI  - Advanced practice nurses. Should they be independent?

PMID- 7812469
TI  - Misdiagnosis of major depression in primary care.

PMID- 7812470
TI  - Alternative medical therapies.

PMID- 7812471
TI  - In-line skating. An observational study of protective equipment used by skaters.
AB  - OBJECTIVES: To determine the frequency and patterns of use of the various types
      of protective equipment by in-line skaters and to determine if use of protective
      equipment was associated with the age, sex, group composition, or expertise of
      the skater. DESIGN: A total of 1548 in-line skaters were observed during a 3
      month period in Milwaukee, Wis. Identification and protective equipment data were
      recorded and analyzed by chi 2 tests with Pearson's correlation coefficient.
      RESULTS: Overall, 491 skaters (31.7%) wore no protective gear. Wrist guards were
      worn by 999 skaters (64.5%). Helmets were worn by only 40 skaters (2.6%).
      Overall, adolescent males, children, and advanced skaters were the least likely
      to be observed wearing protective equipment. CONCLUSIONS: Protective equipment is
      underused by many in-line skaters. Educating in-line skaters about the value of
      wearing protective equipment, as recommended by equipment manufacturers, may help
      reduce the severity or incidence of skating injuries.

PMID- 7812472
TI  - The infrequency of liver function testing in patients using nonsteroidal anti
      inflammatory drugs.
AB  - OBJECTIVE: To describe the monitoring of liver function for patients using
      nonsteroidal anti-inflammatory drugs (NSAIDs), we reviewed the patterns of liver
      function testing in a medium-sized health maintenance organization. METHODS: We
      examined the interval between start of therapy and first performance of a liver
      function test during courses of therapy of the NSAIDs diclofenac sodium, naproxen
      and naproxen sodium, and piroxicam. For comparison, we also studied courses of
      lovastatin as a "positive control," in which the anticipated frequency of liver
      function testing was high. RESULTS: The frequency of liver function tests in
      patients using NSAIDs was generally low, although testing was more common in
      patients who used diclofenac. The probability of liver function testing was
      higher for patients treated in recent calendar years, for patients treated by
      rheumatologists, for patients who previously used NSAIDs, and for patients who
      had undergone a liver function test sometime in the 6 months preceding the onset
      of therapy. CONCLUSION: Physicians ordered liver function tests less frequently
      than recommended, but the observed testing patterns appear rational in light of
      the very low reported frequency of serious hepatic disease in large, monitored
      populations of patients using NSAIDs.

PMID- 7812473
TI  - Upper gastrointestinal tract bleeding in institutionalized mentally retarded
      adults. Primary role of esophagitis.
AB  - BACKGROUND: Upper gastrointestinal (UGI) tract bleeding is a common reason for
      hospitalization of mentally retarded adults. The purpose of this study was to
      determine the frequency and cause of and risk factors for UGI tract bleeding in
      institutionalized mentally retarded adults admitted to our hospital. METHODS:
      Case-control study, with a retrospective review of medical records. SETTING:
      Inner-city tertiary care hospital. PATIENTS: Mentally retarded adults who reside
      in one of three long-term care facilities. MEASUREMENTS: Data on demographic
      features, clinical features, and concurrent medical conditions were collected on
      mentally retarded adults admitted to our hospital for UGI tract bleeding (n =
      40). Data from these patients were compared with those from a control group of
      mentally retarded adults admitted for nonbleeding conditions (n = 124).
      Endoscopic data were reviewed on the patients who bled to further clarify the
      causes of UGI tract bleeding. The patients who bled were compared with those who
      did not bleed using the chi 2 and Mann-Whitney rank sum tests. RESULTS: Upper
      gastrointestinal tract bleeding was the most common reason for hospitalization in
      this patient population. Such bleeding was most commonly caused by erosive
      esophagitis (70% of patients who bled). Conditions associated with an increased
      risk for UGI tract bleeding were hiatal hernia, reduced activity, incontinence,
      hypoalbuminemia, kyphoscoliosis, and spastic quadriplegia. CONCLUSIONS: Upper
      gastrointestinal tract bleeding is a common cause of hospitalization in mentally
      retarded adults and is usually due to erosive esophagitis. It is hoped that
      vigorous efforts to treat gastroesophageal reflux disease may reduce
      hospitalization in these patients.

PMID- 7812474
TI  - Physician office laboratory education and training in primary care residency
      programs.
AB  - OBJECTIVE: To assess the status of office laboratory residency education and
      training in family practice, internal medicine, obstetrics and gynecology, and
      pediatric residency programs. DESIGN: A single mailed survey to 1299 residency
      programs from December 1992 to February 1993. PARTICIPANTS: Primary care
      residency directors from 507 (39%) of 1299 programs. INTERVENTIONS: A 27-item
      survey of residency-based office laboratory practices, education, training, and
      resources. MAIN OUTCOME MEASURES: Differences between specialties in provision
      and quantity of office laboratory education and training, presence of a residency
      based office laboratory, laboratory classification under the Clinical Laboratory
      Improvement Amendments, and available laboratory tests. RESULTS: Of those
      responding, office laboratories were present in 89% of family practice, 19% of
      internal medicine, 29% of obstetrics and gynecology, and 24% of pediatrics
      residency programs. Laboratory training was available at 60% of family practice,
      16% of internal medicine, 15% of obstetrics and gynecology, and 30% of pediatrics
      programs. The median number of hours of formal skills training was 10 hours for
      family practice residency programs but less than 2 hours for the other
      specialties. Only 25% of the programs reported educational assistance from
      pathologists. Merely 4% of the programs had postassessment examinations and 2%
      awarded certificates of achievement. A majority of family practice programs
      performed waivered tests and physician-performed microscopy tests, but moderately
      complex tests were performed in less than 50% of family practice programs.
      CONCLUSIONS: Family practice residency programs provide more office laboratory
      training for residents than other specialties. There is a need for improved
      residency training in the basics of office laboratory practice.

PMID- 7812475
TI  - Frequency of human immunodeficiency virus testing among rural US residents and
      why it is done.
AB  - OBJECTIVE: To examine the frequency with which rural residents' undergo human
      immunodeficiency virus (HIV) antibody testing and the reasons why. DESIGN: Data
      are from the 1991 National Health Interview Survey's supplemental questions on
      knowledge and attitudes about acquired immunodeficiency syndrome. SUBJECTS: The
      respondents were 42,725 adults (aged > or = 18 years), representing a nationwide
      sample of the civilian, noninstitutionalized population of the United States.
      Rural (n = 9903) and urban (n = 32,822) respondents were compared. RESULTS:
      Although 7.1% of rural and 7.9% of urban respondents are at high risk for
      contracting HIV (P = .06), 25.2% of rural and 33.0% of urban respondents had been
      tested for HIV (P = .001). Excluding blood donations, 10.7% of rural and 17.2% of
      urban respondents had been tested for HIV (P = .001). The primary reason between
      the two groups for not getting tested was a belief of being at low risk for
      contracting HIV. Rural respondents were less likely than urban respondents (6.6%
      vs 10.4%) (P = .001) to be tested for HIV in the next 12 months. Rural
      respondents were less informed about HIV risks than were urban respondents. Urban
      residence is a significant predictor of having had an HIV test even after
      controlling for actual risk status, perceived risk status, age, education,
      income, sex, perceived health status, and a scale of knowledge of acquired
      immunodeficiency syndrome risk factors (odds ratio, 1.54; 95% confidence
      interval, 1.37 to 1.73). CONCLUSIONS: Rural residents are less knowledgeable
      about HIV risk factors and are less likely to have been tested for HIV. With the
      increasing rates of infection in rural areas, specific and focused efforts for
      counseling and testing for HIV antibodies in rural areas might prevent and
      control HIV infection and acquired immunodeficiency syndrome.

PMID- 7812477
TI  - Adolescent health and social problems. A method for detection and early
      management. The Dartmouth Primary Care Cooperative Information Project (COOP).
AB  - OBJECTIVE: To develop and test a method for identification and early management
      of the health and social problems of adolescents, many of which go undetected and
      untreated. METHODS: Picture-and-word charts for the measurement of health and
      social problems formed the core of a brief, self-teaching lesson. Other sections
      of the lesson were designed to help teenagers interpret, invent solutions for,
      and communicate concerns about these problems. We examined the impact of the
      lesson on teenagers' understanding of themselves, their feelings, and their
      actions. Two hundred ninety-one adolescents served as subjects for this research.
      RESULTS: Less than 5% of the respondents found the chart-based lesson difficult
      or bothersome in the way it probed personal topics. Ninety percent reported that
      the lesson would have some positive impact on their actions or feelings. Three to
      six weeks after completing the lesson, their opinion of its impact remained high,
      and 36% of the students reported that they had shown it to others outside the
      school. CONCLUSION: A chart-based lesson is well accepted by adolescents and can
      be used to overcome obstacles for the detection and early management of
      adolescents' health and social problems.

PMID- 7812476
TI  - Assessment of documented foot examinations for patients with diabetes in inner
      city primary care clinics.
AB  - BACKGROUND: The established guidelines for a diabetes foot examination include
      assessing circulatory, skin, and neurological status to detect problems early and
      reduce the likelihood of amputation. OBJECTIVE: To determine documented adherence
      with guidelines for foot examinations. SETTING: Four clinics in underserved
      areas. METHODS: Charts of 350 diabetic patients, identified by billing code, were
      reviewed for foot examination documentation. A documented foot examination was
      defined as assessing at least two of the three components of a foot examination.
      The review determined the periodicity and prevalence of foot examinations,
      referrals to a podiatrist or vascular surgeon during a 2-year period, and risk
      factors for foot complications. Stepwise logistic regression was used to
      determine whether risk factors for foot complications predicted foot examination
      status. RESULTS: The patients had a mean age and duration of diabetes of 57.7 and
      8.8 years, respectively; 86% were black or Hispanic. There was no indication of
      foot examination or referral for 55.7% of the patients during the 2-year period.
      Patients with foot care referrals were more likely to have foot examinations by
      their primary care providers (P = .0001). There was almost a fourfold increase in
      the odds that patients with diagnosed peripheral vascular disease had foot
      examinations, with twofold greater odds for each 25-year increase in age.
      CONCLUSIONS: Populations at risk of diabetic complications are unlikely to have
      foot examinations in their primary medical care, but having peripheral vascular
      disease increases the likelihood. Efforts are needed to improve adherence to foot
      examination guidelines for patients with diabetes from underserved populations.

PMID- 7812478
TI  - Types of pain treatment facilities and referral selection criteria. A review.
AB  - Family physicians often come in contact with patients who suffer from chronic
      pain. These patients present a treatment challenge and may require referral to a
      pain treatment facility. The purpose of this review is to define and clarify the
      current concept of a pain treatment facility and delineate the different types of
      treatment facilities available. Possible selection criteria for referral to such
      facilities are suggested, with the rationale for the selection of these criteria.
      The role of the family physician in the treatment by a by a special facility of a
      patient with chronic pain is discussed. By definition, pain treatment facilities
      differ. The family physician should be aware of these differences and selection
      criteria for referral to such facilities.

PMID- 7812479
TI  - The yin and yang of health care system reform. Professional and political
      strategies for setting limits.
AB  - President Clinton's proposed Health Security Act would establish a National
      Health Board (NHB) with three key functions. The NHB would (1) decide which
      services are "medically necessary or appropriate" (Title I, Subtitle B, Section
      1154), (2) "recommend ... appropriate revisions (to the benefit package) ... to
      reflect changes in technology, health care needs, health care costs, and methods
      of service delivery" (Title I, Subtitle F, Section 1503, [a] [2]), and (3)
      "determine a national per capita baseline premium target" (Title VI, Subtitle A,
      Section 6002, [a]), thereby establishing a national health care budget. To date,
      including the work of Mrs Clinton's Task Force on Health Care System Reform,
      there has been little discussion of how the NHB would carry out these
      responsibilities. Critics claim that a budget cap would require rationing.
      Advocates counter that eliminating waste would make rationing unnecessary. In the
      imagined "testimony" that follows, we recommend two strategies to the NHB for
      carrying out its three key functions and for addressing the controversy about
      whether it should consider rationing.

PMID- 7812481
TI  - A comparison of two measures of quality of life: their sensitivity and validity
      for patients with advanced cancer.
AB  - We compared two measures that have been used by professionals to assess the
      quality of life and care of patients with advanced cancer. The Support Team
      Assessment Schedule (STAS) is an instrument for palliative cancer support teams
      to record and evaluate their care; the Hebrew Rehabilitation Centre for the Aged
      Quality of Life (HRCA-QL) index was used in the National Hospice Study (USA) to
      assess patients with advanced cancer. STAS has 17 items, each scaled 0 (best) to
      4 (worst), and HRCA-QL has five items scaled 0 (worst) to 2 (best). The STAS and
      the HRCA-QL were assessed contemporaneously by the members of one support team on
      128 consecutive patients referred over 17 months. Seventy-four patients spent
      more than four weeks in care. Ratings for four out of five HRCA-QL items
      deteriorated significantly in the four to six weeks before death. HRCA-QL index
      items correlated with similar STAS items. Correlations were highest at referral,
      especially in patients seen more than four weeks before death (e.g. symptom
      control (STAS) with health (HRCA-QL) Spearman's rho = -0.64) and the HRCA-QL
      total was correlated with STAS subtotal of six items (rho = -0.45). There were
      few correlations at death. The findings support the validity of both measures for
      the aspects compared, but indicated that STAS was more sensitive to changes in
      patients in the last six weeks of life.

PMID- 7812480
TI  - Measuring the costs and quality of palliative care: a discussion paper.
AB  - In an era of ever increasing emphasis on cost-effectiveness of health care, and
      with the introduction of the internal market, there is now an urgent need for
      information on the costs and quality of palliative care. This paper highlights
      the complexities involved in acquiring and measuring such information and
      discusses methods which were tried out in an exploratory study. The study took
      the form of in-depth case studies in two hospices, one in the voluntary sector
      and one in the NHS.

PMID- 7812482
TI  - Corticosteroids and peptic ulceration.
AB  - The relationship between corticosteroids and peptic ulceration, together with the
      major complications of gastrointestinal haemorrhage and perforation, remains an
      area of clinical concern. This paper reviews the literature regarding peptic
      ulceration and corticosteroids. Risk factors related to an increased incidence of
      peptic ulceration in patients prescribed corticosteroids are discussed. These
      include: total dose of corticosteroid, previous history of peptic ulceration,
      advanced malignant disease and concurrent prescribing of nonsteroidal anti
      inflammatory drugs (NSAIDs). It is suggested that prophylaxis should be
      considered for those patients with two or more risk factors. Choice and efficacy
      of prophylaxis is also considered.

PMID- 7812484
TI  - Hospice referral forms.

PMID- 7812483
TI  - Comparison of metal versus Vialon subcutaneous catheters in a palliative care
      setting.
AB  - In 63 evaluable palliative care patients requiring intermittent bolus
      subcutaneous administration of medication, who were randomly assigned either a
      standard metal subcutaneous needle or a PTFE (Vialon) catheter, there was a
      significantly greater incidence of local reactions at the insertion site with the
      metal needles (9/30) compared with the PTFE catheters (2/33). Despite this, there
      was no significant difference between the two in functional survival. Volume of
      medication injected per day was the best predictor of total time that the
      subcutaneous lines remained in situ.

PMID- 7812485
TI  - Dexamethasone for intractable hiccoughs in a patient with AIDS and PML.

PMID- 7812486
TI  - Pethidine for the treatment of disease related rigors.

PMID- 7812487
TI  - Success rates and failure rates, and causes of failure for common arterial
      reconstructive procedures.

PMID- 7812488
TI  - Reoperative approach for failed aortofemoral, axillofemoral, and femorofemoral
      bypasses.

PMID- 7812489
TI  - Reoperative approaches to failed procedures confined entirely to the abdominal
      aorta.
AB  - Options do exist when the vascular surgeon is faced with failed procedures
      confined to the abdominal aorta. Knowledge of the various techniques outlined
      previously allows an orderly and minimal-risk approach in these patients. Use of
      the original graft is often the first choice to revascularize ischemic lower
      extremities in low-risk patients. Extra-anatomic bypasses are generally reserved
      for high-risk patients. The exception is hepatorenal and splenorenal bypasses
      that are the revascularization method of choice in most patients with failed
      unilateral aortorenal bypasses.

PMID- 7812490
TI  - Reoperative approaches for failed infrainguinal vein grafts.
AB  - The management of patients with thrombosed vein grafts remains a formidable
      challenge for all vascular surgeons. Management strategies will vary based on a
      variety of criteria including the patients' overall condition and symptoms, the
      interval and etiology of graft failure, and the pathological anatomy and
      availability of autogenous vein. A combination of resourcefulness and adherence
      to established vascular surgical principles and techniques will facilitate
      revascularization in the great majority of patients with failed grafts.

PMID- 7812491
TI  - Reoperative approaches for failed infrainguinal polytetrafluoroethylene (PTFE)
      grafts.

PMID- 7812493
TI  - Role of balloon angioplasty and stents in the management of failed arterial
      reconstructions.

PMID- 7812492
TI  - Finding autogenous veins for reoperative lower extremity bypasses: limitations of
      veins other than the greater saphenous.

PMID- 7812494
TI  - Role of arteriovenous fistulas in reoperative lower extremity bypasses.

PMID- 7812495
TI  - The role of stented grafts in the management of failed arterial reconstructions.

PMID- 7812496
TI  - Reoperative approaches for carotid restenosis.

PMID- 7812497
TI  - Role of thrombolytic, antiplatelet, antithrombotic, and other drugs in the
      management of failed arterial grafts.

PMID- 7812498
TI  - On the classification capability of a dynamic threshold neural network.
AB  - This paper proposes a new type of neural network called the Dynamic Threshold
      Neural Network (DTNN) which is theoretically and experimentally superior to a
      conventional sigmoidal multilayer neural network in classification capability.
      Given a training set containing 4k + 1 patterns in Rn, to successfully learn this
      training set, the upper bound on the number of free parameters for a DTNN is (k +
      1)(n + 2) + 2(k + 1), while the upper bound for a sigmoidal network is 2k(n + 1)
      + (2k + 1). We also derive a learning algorithm for the DTNN in a similar way to
      the derivation of the backprop learning algorithm. In simulations on learning the
      Two-Spirals problems, our DTNN with 30 neurons in one hidden layer takes only
      3200 epochs on average to successfully learn the whole training set, while the
      single-hidden-layer feedforward sigmoidal neural networks have never been
      reported to successfully learn the given training set even though more hidden
      neurons are used.

PMID- 7812499
TI  - Average case analysis of an Hebb-type rule that finds the network connectivity.
AB  - We describe an Hebb-type algorithm for learning unions of nonoverlapping
      perceptrons with binary weights. Two perceptrons are said to be nonoverlapping if
      they do not share any input variables. The learning algorithm is able to find
      both the network architecture and the weight values necessary to represent the
      target function. Moreover, the algorithm is local, homogeneous, and simple enough
      to be biologically plausible. We investigate the average behavior of this
      algorithm as a function of the size of the training set. We find that, as the
      size of the training set increases, the hypothesis network built by the algorithm
      "converges" to the target network, both in terms of the number of perceptrons and
      the connectivity. Moreover, the generalization rate converges exponentially to
      perfect generalization as a function of the number of training examples. The
      analytic expressions are in excellent agreement with the numerical simulations.
      To our knowledge, this is the first average case analysis of an algorithm that
      finds both the weight values and the network connectivity.

PMID- 7812500
TI  - Optimal Hebbian learning rules and the role of asymmetry.
AB  - We study the storage properties associated with generalized Hebbian learning
      rules which present four free parameters that allow for asymmetry. We also
      introduce two extra parameters in the post-synaptic potentials in order to
      further improve the critical capacity. Using signal-to-noise analysis, as well as
      computer simulations on an analog network, we discuss the performance of the
      rules for arbitrarily biased patterns and find that the critical storage capacity
      alpha c becomes maximal for a particular symmetric rule (alpha c diverges in the
      sparse coding limit). Departures from symmetry decrease alpha c but can increase
      the robustness of the model.

PMID- 7812501
TI  - Incorporating production rules with spatial information onto a neocognitron
      neural network.
AB  - Rule-embedded neocognitron (REN) is proposed where the knowledge base of a
      neocognitron is constructed through incorporating production rules into its
      interlayer connections. Prototype patterns training is not required. The semantic
      of interlayer connections is established. The resulting network can now be
      analyzed according to the rule structure and problematic portions can be
      corrected. We demonstrate the ease with which performance can be improved by
      applying REN on handwritten numeral recognition. The same set of handwritten
      numerals initiated by Fukushima is used to test this methodology. It is found
      that the performance is comparable with that of Fukushima's neocognitron with
      supervised training.

PMID- 7812502
TI  - Constrained learning vector quantization.
AB  - Kohonen's learning vector quantization (LVQ) is an efficient neural network based
      technique for pattern recognition. The performance of the method depends on
      proper selection of the learning parameters. Over-training may cause a
      degradation in recognition rate of the final classifier. In this paper we
      introduce constrained learning vector quantization (CLVQ). In this method the
      updated coefficients in each iteration are accepted only if the recognition
      performance of the classifier after updating is not decreased for the training
      samples compared with that before updating, a constraint widely used in many
      prototype editing procedures to simplify and optimize a nearest neighbor
      classifier (NNC). An efficient computer algorithm is developed to implement this
      constraint. The method is verified with experimental results. It is shown that
      CLVQ outperforms and may even require much less training time than LVQ.

PMID- 7812503
TI  - A storage algorithm for two-layered neural networks.
AB  - A learning algorithm for the two-layered committee machine is proposed. The proof
      of its convergence in a finite time is given. Its efficiency is compared to the
      simple exhaustive enumeration of the internal representations of the training
      set.

PMID- 7812504
TI  - Gelfand-Tsetlin principle of minimal afferentation and bistability of dendrites.
AB  - Neurons with bistable dendrites may fire persistently without persistent synaptic
      excitation while transient afferentation shifts the frequency of the persistent
      firing. These neurons change the firing frequency until they minimize their
      afferential input in a properly designed network. The afferentation minimum in
      this network is a stable state. The concept of the stable afferentation minimum
      generalizes Feldman's spring model of muscle control. An oversimplified network
      imitating the gamma-loop demonstrates the above statements.

PMID- 7812505
TI  - Map formation in proprioceptive cortex.
AB  - Current understanding of feature maps in proprioceptive cortex is quite limited.
      To complement experimental studies, we developed a computational model of map
      formation in proprioceptive cortex. Muscle length and tension from six muscle
      groups controlling the position of a model arm in three-dimensional space served
      as input to the simulated cortex. The resultant feature map consisted of
      regularly spaced clusters of cortical columns representing individual muscle
      lengths and tensions. Cortical units became tuned to plausible combinations of
      tension and length, and multiple representations of each muscle group were
      present. The map was organized such that compact regions within which all muscle
      group lengths and tensions are represented could be identified. Most striking was
      the observation that, although not explicitly present in the input, the cortical
      map developed a representation of the three-dimensional space in which the arm
      moved. These findings represent testable predictions about proprioceptive cortex,
      and may also help clarify some organizational issues concerning primary motor
      cortex.

PMID- 7812506
TI  - Chronic viral hepatitis B and C: an argument against the conventional
      classification of chronic hepatitis.
AB  - The classification of chronic hepatitis distinguishing benign chronic persistent
      hepatitis from severe chronic active hepatitis was constructed without knowledge
      of well-defined aetiological factors. Better understanding of the different
      hepatitis-viruses has shed new light on this subject. Chronic viral hepatitis B
      and C each show typical histological patterns. The validity of the conventional
      classification has been evaluated by a comparative study of chronic viral
      hepatitis B and C. 130 biopsies from 110 patients with chronic hepatitis C (CH-C)
      proven serologically by antibodies (second generation testing) were compared with
      105 biopsies from 73 patients with chronic hepatitis B (CH-B). These were scored
      semi-quantatively. In CH-C, lymphoid follicles and/or aggregates were found in
      88.5%, fatty degeneration in 51%, bile duct lesions in 46.2%, and Mallory body
      like material in the hepatocytes in 9.2%. The portal lymphocytic infiltration
      generally predominated over the necro-inflammatory lesions of the parenchyma.
      Chronic persistent hepatitis (defined by the presence of portal hepatitis) was
      present exclusively in CH-C. Chronic lobular hepatitis was found exclusively in
      CH-B. We conclude that the histological criteria described for CH-C are highly
      suggestive of the diagnosis, that the artificial subdivision of chronic hepatitis
      into CPH and CAH is obsolete and that the histological assessment of chronic
      hepatitis should consist of a grading of inflammatory activity (minimal, mild,
      moderate, severe) and staging of fibrosis (extent of distortion of architecture).
      The final diagnosis should be based on the demonstration of the aetiological
      agent.

PMID- 7812507
TI  - Comparative evaluation of integrin alpha- and beta-chain expression in colorectal
      carcinoma cell lines and in their tumours of origin.
AB  - The integrin family consists of broadly expressed cell surface adhesion
      receptors, each member of which is composed of a non-covalently linked alpha/beta
      heterodimer. Integrin receptors are involved in the interaction with matrix
      proteins and may contribute to invasion and metastasis of carcinomas. To examine
      the biological role integrins play in colorectal carcinoma we compared the
      expression of integrin alpha- and beta-subunits in situ and in vitro. Eight newly
      established cell lines derived from immunohistochemically characterized
      colorectal carcinomas together with two sublines obtained after nude mouse
      passage and the commonly used colon carcinoma lines HT-29, SW480, SW620, and COLO
      205 were investigated by immunocytochemistry and flow cytometry. The carcinomas
      in situ expressed alpha 1-, alpha 2-, alpha 3-, alpha 6-, alpha v- and beta 1
      subunits in variable amounts while being devoid of alpha 4, alpha 5, and beta 3.
      The individual integrin profile of the tumour in tissue was essentially
      maintained in vitro. However, a neo expression of the alpha 5 chain was found,
      together with an induction or increase in alpha 1, alpha 2, alpha 3, alpha v and
      beta 1 levels. No decrease in integrin subunit expression was observed. Standard
      serum and serum-free medium revealed no striking differences in alpha- and beta
      chain expression in the cell lines HT-29 and COLO 205. In serum-free medium,
      SW480 showed a slight increase of alpha 1 and alpha 5 and a decrease of alpha 3
      and alpha v while SW620 expressed more alpha 1. We conclude that the great
      variability of adhesion receptor expression of the integrin family in colorectal
      carcinomas in situ is essentially maintained in vitro, although culture
      conditions which are only marginally influenced by serum factors unpredictably
      lead to some increase in expression or even induction of several integrin
      subunits.

PMID- 7812508
TI  - Metastatic potential of small and minimally invasive breast carcinomas.
AB  - Invasive ductal mammary carcinomas (IDC) of 1 cm in tumour size or less account
      for less than 20% of all IDC. We have observed 167 such cases at our Institution
      between 1985 and 1989. These were divided into carcinomas with an extensive or
      predominant intraductal component (EIC or PIC, being least 2x or 4x larger than
      the invasive component; 90) and compared statistically with the control group (no
      EIC or PIC; 77) for known prognostic factors and for their metastatic behaviour.
      Lymph nodes were step sectioned in order to detect occult micrometastases. The
      median follow up time was 62.6 months. Lymph node metastases were seen in 10% of
      pT1a and 19% of pT1b cases. Significant differences were found when comparing the
      EIC/PIC group with the control group (pT1a: 11% vs. 0%, pT1b: 37% vs. 11% lymph
      node metastases). Also, axillary and infraclavicular recurrence rates were higher
      for EIC/PIC carcinomas compared with other IDC of < or = 1 cm (9.3% vs. 4.2%).
      This significantly adverse metastatic behaviour of the EIC/PIC tumours may be in
      part due to the more frequent occurrence of multifocal tumours in this group (in
      43% vs. 6%), resulting in a greater tumour burden. We conclude that the overall
      risk of lymph node metastasis is not negligible in carcinomas of 1 cm or less in
      diameter with the risk being more than doubled for carcinomas with an intraductal
      component exceeding the invasive tumour by a factor of two. These differences
      were relevant only to regional metastases; the risk for distant metastasis and
      survival was identical after 5 years.

PMID- 7812509
TI  - A comparison of large block macrosectioning and conventional techniques in breast
      pathology.
AB  - Two techniques for the histological handling of breast specimens, namely
      conventional sampling using small blocks (SB) and a large block (LB)
      macrosectioning technique have been compared, with special emphasis on tumour
      size and in situ carcinoma, in an attempt to objectively demonstrate the
      advantages of the latter method. This is considered to be of particular
      importance in guiding the clinicians in their use of the many treatment
      modalities available for breast carcinoma. All cases were from the routine
      surgical caseload; 100 examined by the LB technique and 111 using conventional
      SB. The LB technique gave a reliable measurement of invasive carcinoma in 100% of
      cases compared to only 63% of SB cases. Ductal carcinoma in situ (DCIS), was
      found more frequently (80% versus 64%) and its extent was more easily and
      reliably measured in the large blocks. The extent of DCIS was significantly
      greater in all cases using large block techniques. Concurrent carcinomas were
      found more frequently in the LB series and these tumours were smaller than those
      in the SB series. Similar differences were noted with radial scars, and other
      proliferative lesions also had a higher incidence in the LB series. We conclude
      that the LB technique has sufficient advantages to recommend it as a standard
      technique in breast pathology.

PMID- 7812511
TI  - Immunohistochemical localization of endothelin-1 in non-neoplastic and neoplastic
      adrenal gland tissue.
AB  - Endothelin (ET)-1 is a 21-amino acid peptide with potent vasopressor and
      vasocontrictive properties. Biochemical studies suggest that this peptide occurs
      in adrenal glands, where it influences steroid hormone production. However, we
      have found no report of the topographical distribution of this peptide. The
      localization of ET-1 immunoreactivity in non-neoplastic (37 cases) and neoplastic
      adrenal glands (48 cases) was investigated with a sensitive immunohistochemical
      technique applied to routinely processed tissue specimens. ET-1 immunoreactivity
      was regularly seen in the cortex, especially in the zona fasciculata and to a
      varying extent also in the other two zones, but not in the medulla. The
      immunoreactive material appeared in the cytoplasm mostly in the form of vacuolar
      structures but also as grains. Focally, the cell membrane also showed
      immunoreactive staining. In the zona reticularis the immunoreactivity appeared
      mainly as cytoplasmic grains. Most cortical adenomas displayed numerous
      immunoreactive cells. The immunoreactivity in the tumour tissue appeared in the
      same forms as in normal cortex, but the reactive products were generally fewer in
      number. No obvious differences in immunostaining were seen between the
      aldosterone- and cortisol-producing adenomas or the non-functioning ones. Three
      of the ten carcinomas contained immunoreactive cells, but they were few,
      appearing focally and the ET-1 immunoreactive structures were seen as 'dust-like'
      material. The difference in immunoreactivity between the benign and the malignant
      cortical neoplasms may be of diagnostic value. Functionally our results support a
      relationship between ET-1 and steroid regulation in non-neoplastic cortical
      tissue.

PMID- 7812510
TI  - Expression of human T-cell leukaemia virus type I and associated antigens, and
      interleukin-2 and receptor in lymph nodes of adult T-cell leukaemia/lymphoma.
AB  - To examine the relationship between the expression of human T-cell leukaemia
      virus type (HTLV-I) mRNA and associated antigens and clinicopathological
      features, we studied 31 lymph nodes of patients with adult T-cell
      leukaemia/lymphoma (ATLL) and related diseases, using in situ hybridization and
      immunohistochemistry. We classified the patients into four types on the basis of
      their clinicopathological features (HTLV-I associated lymphadenitis, incipient
      ATLL, ATLL with complete HTLV-I provirus, and ATLL with defective HTLV-I
      provirus. The expression of HTLV-I mRNA was detected in all 3 patients with
      incipient ATLL, in 5 of 10 patients with defective-provirus ATLL, in 5 of 11
      patients with complete-provirus ATLL, and 3 of 7 with HTLV-I associated
      lymphadenitis, but the amounts were very small; approximately 1 in 10000-200000
      lymph node cells express the viral genomes. This suggests that expression of
      viral genomes may not be important for immortalization, but it is important that
      to note the capacity for HTLV-I infection is preserved in each group of non
      neoplastic and neoplastic states. HTLV-I mRNA was detected only in lymphocytes
      and/or lymphoma cells, but the HTLV-I associated antigens (env, gag and pX) were
      found in histiocytes and endothelial cells, as well as in lymphocytes and/or
      lymphoma cells. Anti-interleukin 2 receptor (IL-2R) antibody reacted with the
      giant cells of incipient ATLL and with the transformed lymphocytes and
      immunoblast-like cells of the HTLV-I-associated lymphadenitis but not with the
      lymphocytes in the background. Of the typical ATLL, IL-2R was found in both
      lymphoma cells and giant cells. IL-2 was rarely detected.

PMID- 7812512
TI  - Nucleolar and argyrophilic nucleolar organizer region counts in urothelial
      carcinomas with special emphasis on grade II tumors.
AB  - Prognostic assessment of bladder carcinomas of intermediate differentiation is
      difficult. This study therefore investigated the prognostic values of nucleolar
      status and silver staining of argyrophilic nucleolar organizer regions (AgNORs)
      in grade II bladder carcinomas. In biopsies from 34 grade II transitional cell
      carcinomas of the urinary bladder the number of nuclei with nucleoli, the
      location of nucleoli within the nucleus and the number of AgNORs were determined
      in 1000 or 200 nuclei per section respectively. Ten biopsies showing normal
      urothelium, 18 cases with mild to severe atypia, 27 grade I, 34 grade II and 12
      grade III transitional cell carcinomas were also studied. Significantly differing
      nucleolar and AgNOR values were found comparing normal urothelium/grade I
      carcinomas with severe urothelial atypia/grade III carcinomas. Grade II
      carcinomas, however, were inhomogeneous. One subgroup had nucleolar and AgNOR
      values resembling grade I carcinomas while the second group had values similar to
      those of grade III carcinomas. This subdivision of grade II carcinomas correlates
      with results reported for DNA-cytometry. The results suggest a subdivision of
      patients with grade II transitional cell carcinomas into a low risk and high risk
      group.

PMID- 7812513
TI  - Light chain deposition disease of the kidney. Morphological aspects in 24
      patients.
AB  - Renal biopsies and autopsy specimens of 23 patients with light chain deposition
      disease (LCDD) and one with only heavy chain deposits, were studied by light (LM)
      and electron microscopy (EM) as well as immunohistology (IH). Thirteen patients
      had multiple myeloma; 1 had lymphoma, and 1 chronic myeloid leukaemia with
      polycythaemia vera. In nine patients, no lymphoproliferative disease was
      identified. The LM lesions most suggestive of LCDD, nodular glomerulosclerosis
      (NS) and thickening and wrinkling of the tubular basement membranes (TBM), were
      present in only ten and 13 patients, respectively. In five of seven specimens
      without NS or TBM thickening by LM, EM was negative, indicating a limited value
      of EM in confirming the diagnosis. Renal amyloidosis was not identified, but in
      one patient amyloid in the heart and tongue was seen at autopsy. One patient had
      both granular and extensive glomerular non-amyloid fibrillary deposits. In two
      patients myeloma casts were identified. Twenty-one patients showed renal LC
      immune reactivity, 1 had both alpha heavy and lambda LC, 1 had only detectable
      gamma heavy chain. One biopsy was negative by IH, but had characteristic electron
      dense deposits. In six patients with immune reactivity to LC, no electron dense
      deposits could be identified by EM. This study emphasizes the spectrum of renal
      changes by LM and EM in LCDD, the frequent lack of consistency between deposits
      detected by IH and EM and the difficulty in coming to a definite diagnosis
      without LM, EM and IH. The results of this study and examination of the
      literature indicates that extensive morphological changes are more often present
      in kappa than in lambda LCDD.

PMID- 7812514
TI  - Tubular dilatation in the repair process of ischaemic tubular necrosis.
AB  - To elucidate the mechanisms of renal tubular dilatation in acute tubular necrosis
      (ATN), morphological findings after 60 min ischaemia were studied in rats. The
      characteristics of the tubular basement membrane (BM) were also examined. A
      morphometric analysis of cell proliferation, epithelial cellularity and the
      circumference of damaged tubules was performed. The ischaemic injury resulted in
      widespread necrosis of renal tubules at day 1, and the BM of damaged tubules
      appeared thin. The intensity of the immunohistochemical staining for BM
      components decreased. The epithelial cell proliferation was particularly active
      in the early phase. Dilatation of the damaged tubules began at day 2, and the
      degree of dilatation increased up to day 6. Regenerative epithelial hyperplasia
      occurred and abnormalities of tubular BM were seen. Epithelial hyperplasia and
      dilatation of damaged tubules was most prominent at day 6 and the tubular BM was
      thickened by newly produced BM components. Tubular obstruction was not seen and
      tubules returned to normal size by day 28. Epithelial hyperplasia and
      abnormalities of tubular BM disappeared progressively. Regenerative tubular
      epithelial hyperplasia and abnormalities of tubular BM may play an important role
      in pathogenesis of tubular dilatation in ATN, and tubular dilatation is not due
      to tubular obstruction.

PMID- 7812515
TI  - Laryngeal papillomatosis: molecular, histopathological, and clinical evaluation.
AB  - Molecular, histopathological, and clinical studies were carried out on a series
      of 79 laryngeal papillomas (LP) from 36 patients in order to investigate the
      hypothesis that juvenile and adult LP may represent a biological entity causally
      related to Human papilloma virus (HPV) infection. Using in situ hybridization
      with biotin-labelled probes and polymerase chain reaction, we detected human
      papilloma virus (HPV) 6/11 in 28 of 29 juvenile LP, in 26 of 30 adult multiple,
      and in 17 of 20 adult solitary LP. None of LP was found to harbour HPV types 16,
      18, 31, 33, and 51. There were no clear-cut histological differences between
      juvenile and adult LP, the presence of koilocytosis was equally observed in both,
      and there was no prevalent type of epithelial hyperplasia in either form, except
      that all three cases of atypical hyperplasias (precancerous lesions) were found
      among adult patients. During a 14 year follow-up, no carcinomatous transformation
      of LP was observed. All juvenile LP in our study had frequent recurrences of the
      disease, however, numerous surgical procedures were also required in 16 of 27
      adult patients. Our study supports Lindeberg's hypothesis of a similar
      pathogenesis for all forms of LP caused by the HPV types 6/11.

PMID- 7812516
TI  - A surface replica method: a useful tool for studies of the cytoskeletal network
      in red cell membranes of normal subjects and patients with a beta-spectrin mutant
      (spectrin Le Puy: beta 220/214).
AB  - Visualization of the components of the red cell membranes, and especially the
      structure of cytoskeletal proteins in situ, has become a requisite in studies of
      red cell membrane disorders. There has been a search for a consistent and
      dependable method for detecting these structures. In the present study, the
      surface replica method was used with transmission electron microscopy to examine
      the cytoskeletal network of the red cell ghosts of a normal control and patients
      with a beta-spectrin mutant (beta-spectrin Le Puy). The surface replica method is
      well-suited to observation of the cytoskeletal network of the membranes in a
      nearly native in situ condition. Immunogold labelling with anti-membrane protein
      antibodies is easily applicable to the identification of each component of the
      cytoskeletal proteins. The findings obtained under normal and pathological
      conditions using the surface replica method corresponded with those made by the
      quick-freeze, deep-etching method.

PMID- 7812518
TI  - Giant cell reparative granuloma of the distal skeletal bones. A report of five
      cases with immunohistochemical findings.
AB  - Giant cell reparative granuloma (GCRG) is a reactive bone lesion that most often
      involves the jaws. However, occasional cases of GCRG in the distal extremities
      have been reported, to which we add five cases. All the patients were young to
      middle-aged adults and had sharply bordered, lytic lesions. Histologically, all
      the lesions had areas of osteoclast-like giant cells and osteoblast mantled
      osteoid. Two of the cases had foci of osteoclast-like giant cells lining vascular
      spaces. In extragnathic locations, GCRG may simulate other osteolytic giant cells
      lesions such as giant cell tumour of bone and aneurysmal bone cyst (AnBC).
      Immunohistochemically, all cases showed positive staining of the stromal spindle
      cells for vimentin and actin, and of the osteoclast-like giant cells for CD68,
      vimentin and leucocyte common antigen. GCRG is a benign lesion and conservative
      therapy is curative. As GCRG may have histological features which resemble AnBC
      it may be considered to be the solid variant of AnBC.

PMID- 7812517
TI  - Immunocytochemical and ultrastructural heterogeneities of normal and
      glibenclamide stimulated pancreatic beta cells in the rat.
AB  - When studied morphologically in semi-thin sections in the rat in vivo, pancreatic
      beta cells displayed heterogeneous immunoreactivities for insulin and amylin,
      depending on the islet size and the intra islet position of the beta cells. In
      larger islets, cortical beta cells (beta cells with contacts with all islet cell
      types and with the exocrine parenchyma) which are located in the periphery were
      more densely immunostained for insulin and amylin than medullary beta cells (beta
      cells with contacts only with other beta cells) which are located in the centre
      of the islet. Ultrastructurally, these findings were accompanied by differences
      in the number of secretory granules and mitochondria. Beta cells in small islets
      and at extra-islet sites exhibited a dense immunoreactivity. After administration
      of glibenclamide, immunoreactivities for insulin and amylin were diminished in a
      time-dependent manner, decreasing first in medullary and thereafter in cortical
      beta cells of larger islets. Ultrastructurally, the beta cells exhibited the
      typical signs of stimulation. A minority of beta cells in small islets and all
      beta cells in extra-islet locations remained unchanged. Thus pancreatic beta
      cells under basal and stimulatory conditions in vivo exhibit heterogeneity in
      hormone content and in ultrastructural features. These differences may represent
      the basis for a functional heterogeneity of the insulin secretory response of the
      individual beta cell both in vivo and in vitro in states of normal and impaired
      insulin secretion. As heterogeneity was observed only among beta cells in islets,
      while single beta cells surrounded by acinar cells exhibited no changes in
      insulin immunoreactivity, interactions between beta cells as well as between beta
      cells and other endocrine cells may be critical for expression of heterogeneity
      within the beta cell population.

PMID- 7812519
TI  - Detection of Epstein Barr virus in an hepatic leiomyomatous neoplasm in an adult
      human immunodeficiency virus 1-infected patient.
AB  - We report the first case of a human immunodeficiency virus (HIV)-related primary
      hepatic leiomyoma in an adult patient. The diagnosis was made at autopsy and
      confirmed by immunohistochemistry. Epstein Barr virus (EBV) was identified in
      tumour cells by in situ hybridization. Review of the literature revealed 13 cases
      of visceral myogenic tumours occurring in acquired immunodeficiency syndrome
      children, and only 2 cases in adults. One was a spinal epidural leiomyoma, the
      other multiple smooth muscle tumours of the colon and adrenal gland. This is the
      first report of EBV in smooth muscle neoplastic cells in an HIV-infected adult
      patient.

PMID- 7812520
TI  - Centrocytic-like lymphoma associated with localized amyloidosis of the large
      intestine.
AB  - A case of low-grade centrocytic-like (CCL) B-cell lymphoma involving the large
      intestine, the regional lymph nodes and the spleen is reported. In the large
      intestine the lymphomatous infiltrate was restricted to sites of intense
      antigenic stimulation (diverticula, appendix, ileo-caecal valve) and was
      associated with marked plasma cell differentiation and massive amyloid deposits.
      The immunophenotype was CD20, CD21, CD45RA/MB1/MT2, CD68, CD45 related/Ki-B3 and
      HLA-DR positive, and MB2, DBA.44 reactive regarding the CCL cell lymphoma
      subpopulation; and IgG-lambda positive regarding its plasma cell fraction.

PMID- 7812521
TI  - Intrathyroid salivary gland-type tissue in multinodular goiter.
AB  - We report a case of intrathyroid salivary gland tissue in a 66-year-old Caucasian
      female with multinodular goiter. Lobules of well differentiated seromucinous
      salivary glands were found in close relationship with cartilage and fat, and
      intimately associated with normal thyroid follicles and solid cell nests (SCN) of
      the thyroid gland. This is the first report of non-neoplastic intrathyroid
      salivary gland tissue. We conclude that this heterotopic tissue probably arises
      from the SCN as ultimobranchial vestigial structures.

PMID- 7812522
TI  - Analysis of genetic alterations in renal cell carcinoma using the polymerase
      chain reaction.

PMID- 7812523
TI  - [Teaching public health in IFSI].

PMID- 7812524
TI  - [Education-action and anthropological approach].

PMID- 7812525
TI  - [Inquiry: practical course in public health: pedagogical orientation].

PMID- 7812526
TI  - [Experience of educating nursing students in health education].

PMID- 7812527
TI  - [Ethics and public health].

PMID- 7812528
TI  - [Introduction of a student promotion by school health nurses].

PMID- 7812529
TI  - [Franco-Roumanian exchanges: realities and perspectives].

PMID- 7812530
TI  - [Pedagogical course for a public health action project in Guyana].

PMID- 7812532
TI  - [Towards a definition of health sciences and social sciences].

PMID- 7812531
TI  - [The management generation].

PMID- 7812533
TI  - [Hommage to Simone Chaze].

PMID- 7812534
TI  - [Emergency care and nursing diagnosis].

PMID- 7812535
TI  - [Apprenticeship contract: a new partnership for education in nursing care].

PMID- 7812536
TI  - [Software for the instruction of nursing diagnosis].

PMID- 7812537
TI  - Patient-ventilator interaction during synchronized intermittent mandatory
      ventilation. Effects of flow triggering.
AB  - Synchronized intermittent mandatory ventilation (SIMV) intermixes assisted and
      spontaneous breaths. Its ability as a weaning technique has been questioned on
      the basis that patients show little adaptation to ventilator assistance. We
      studied inspiratory effort and patient-ventilator interaction at different levels
      (SIMV, 100, 50, and 0%) of flow-triggered SIMV versus pressure-triggered SIMV in
      patients during the weaning period. The two triggering systems were evaluated
      during constant flow and constant pressure mandatory SIMV breaths. Inspiratory
      effort was estimated as the esophageal pressure time product (PTP) per breath
      (PTP/b) and per minute (PTP/min). The PTP/b and PTP/min of both mandatory and
      spontaneous breaths were significantly lower during flow triggering than during
      pressure triggering SIMV, irrespective of the ventilatory mode. During pressure
      triggered SIMV PTP/b and PTP/min were identical for mandatory and spontaneous
      breaths, whereas during flow-triggered SIMV PTP/b and PTP/min were significantly
      lower for mandatory than for spontaneous breaths. This difference was greatest
      when flow triggering and constant pressure ventilation were associated. These
      data show that flow triggering reduces inspiratory effort during both mandatory
      and spontaneous SIMV breaths and obtains a better patient-ventilator interaction.

PMID- 7812538
TI  - Effect of cooling on oxygen consumption in febrile critically ill patients.
AB  - Hyperthermic critically ill patients are commonly cooled to reduce their oxygen
      consumption (VO2). However, no previous studies in febrile humans have measured
      VO2 during cooling. We cooled 12 febrile, critically ill, mechanically ventilated
      patients while measuring VO2 and CO2 production (VCO2) by analysis of inspired
      and expired gases. All patients were mechanically ventilated for hypoxemic,
      hypercapneic, or shock-related respiratory failure and had a mean APACHE II score
      of 22.4 +/- 7.7. As temperature was reduced from 39.4 +/- 0.8 to 37.0 +/- 0.5
      degrees C, VO2 decreased from 359.0 +/- 65.0 to 295.1 +/- 57.3 ml/min (p < 0.01)
      and VCO2 decreased from 303.6 +/- 43.6 to 243.5 +/- 37.3 ml/min (p < 0.01). The
      respiratory quotient (RQ) did not change significantly, and calculated energy
      expenditure decreased from 2,481 +/- 426 to 1,990 +/- 33 kcal/day (p < 0.01). In
      7 patients with right heart catheters, cardiac output decreased from 8.4 +/- 3.2
      to 6.5 +/- 1.8 L/min (p < 0.01) as the oxygen extraction fraction also tended to
      decrease from a mean of 28.2 +/- 6.8 to 23.4 +/- 4.7% (p = 0.12) during cooling.
      Accordingly, cooling the febrile patient unloads the cardiorespiratory system
      and, in situations of limited oxygen delivery or hypoxemic respiratory failure,
      may thus facilitate resuscitation and minimize the potential for hypoxic tissue
      injury.

PMID- 7812539
TI  - Systemic and gut O2 extraction during endotoxemia. Role of nitric oxide
      synthesis.
AB  - Endotoxin administration decreases intrinsic responsiveness of arteries to
      contractile agonists, both in vivo and in vitro. Endotoxin also impairs systemic
      and intestinal ability to increase microvascular O2 extraction in response to
      decreases in O2 delivery. During endotoxemia, contractile responsiveness can be
      increased by stereospecific inhibitors of nitric oxide (NO) synthase, suggesting
      that the hypotension and loss of microvascular function caused by endotoxin may
      result from increased nitric oxide biosynthesis. This study tested whether
      inhibition of NO synthesis could reverse the systemic and intestinal oxygen
      extraction defects seen after endotoxin challenge in the dog. Oxygen extraction
      and hemodynamic responses to progressive decreases in O2 delivery (stagnant
      hypoxia) were measured systemically and in isolated autoperfused intestine
      segments in anesthetized dogs. Systemic and intestinal O2 extractions at the
      onset of O2 supply dependency were significantly impaired in endotoxin-challenged
      (n = 6) compared with control (n = 7) animals. Inhibition of NO synthase activity
      with N omega-nitro-L-arginine methyl ester (L-NAME), 50 mg/kg + 100 mg/kg/h,
      completely inhibited endothelium-dependent vasodilation responses evaluated in
      vitro, and significantly but incompletely reversed the systemic hypotension in
      animals previously given endotoxin (n = 9). Despite this improvement, critical O2
      extraction ratios remained significantly reduced. Administration of L-NAME in the
      absence of endotoxin (n = 8) significantly increased systemic vascular resistance
      and decreased cardiac output and O2 delivery, but it did not impair critical O2
      extraction ratios in whole body or isolated intestine. We conclude that
      inhibition of NO synthesis in this model of endotoxemia can improve arterial
      pressure without improving those microvascular functions that may influence
      tissue O2 extraction efficacy.

PMID- 7812540
TI  - Improvement in VA/Q distributions during inhalation of nitric oxide in pigs with
      methacholine-induced bronchoconstriction.
AB  - Effects of nitric oxide (NO) and aerosolized terbutaline inhalation on
      ventilation-perfusion (VA/Q) distributions were determined during methacholine
      induced bronchoconstriction in nine mechanically ventilated pigs. Animals
      inhaled, in random order, zero, 20, and 80 parts per million (ppm) of NO or
      aerosolized terbutaline. Inhalation of either 20 ppm NO or terbutaline produced
      similar reduction in pulmonary resistance and increase in lung compliance.
      Bronchodilation was most pronounced during inhalation of 80 ppm NO. NO inhalation
      increased PaO2 from 65 +/- 4 to 90 +/- 5 (20 ppm NO) and 104 +/- 6 mm Hg (80 ppm
      NO) (p < 0.05), and oxygen delivery (DO2) from 484 +/- 49 to 565 +/- 25 (20 ppm
      NO) and 619 +/- 43 ml/kg/min (80 ppm NO) (p < 0.05) compared with control.
      Aerosolized terbutaline did not increase PaO2 and DO2. NO inhalation accounted
      for a decrease in blood flow to shunt units (20 ppm NO: 14 +/- 1%, 80 ppm NO: 19
      +/- 2%; p < 0.05) and an increase in the perfusion of normal VA/Q units (20 ppm
      NO: 12 +/- 1%, 80 ppm NO: 18 +/- 1%; p < 0.05). Perfusion of shunt and normal
      VA/Q units was similar in the absence of NO inhalation with and without
      aerosolized terbutaline. Pulmonary vascular resistance decreased from 510 +/- 55
      to 332 +/- 22 dyn.s/cm5 with 20 ppm NO (p < 0.05) and to 329 +/- 41 dyn.s/cm5
      with 80 ppm NO (p < 0.05) but did not change with terbutaline.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7812541
TI  - Effects of fatigue on force-velocity relation of diaphragm. Energetic
      implications.
AB  - Characteristics of the force (P)-velocity (V) relationship were investigated
      before and after fatigue in isolated diaphragm muscle of two species: mouse (n =
      12), in which diaphragm is composed almost exclusively of fast-twitch fatigue
      resistant fiber type, and rat (n = 12), in which diaphragm contains both fatigue
      sensitive and fatigue-resistant fiber types. Following fatigue protocol, the
      mechanical performance of both the contraction and relaxation phases were
      significantly depressed in the two species. Consequences of the fatigue procedure
      on P-V characteristics differed markedly according to the two species. In mouse
      diaphragm, fatigue trial did not change the G curvature of the P-V hyperbola, the
      maximum mechanical efficiency Effmax, or the normalized peak power output M2.
      Conversely, in rat diaphragm, fatigue resulted in higher G curvature (p < 0.001),
      higher Effmax (p < 0.001) and a lower M2 (p < 0.001) compared with control
      values. This suggests that fatigue improved the economy of force generation in
      mixed rat diaphragm and not in mouse. This is consistent with an increased
      proportion of slow fatigue-resistant fibers caused by fatigue of fast fatigue
      sensitive fibers in rat diaphragm.

PMID- 7812542
TI  - Accelerated course of human immunodeficiency virus infection after tuberculosis.
AB  - To determine the effect of active tuberculosis on survival and the incidence of
      opportunistic infections in HIV-infected patients, we performed a retrospective
      cohort study at four U.S. medical centers to compare the survival and incidence
      rate of opportunistic infections in 106 HIV-infected patients with active
      tuberculosis (cases) with that of 106 HIV-infected patients without tuberculosis
      (control subjects) but with a similar level of immunosuppression (measured by the
      absolute CD4+ lymphocyte count) as the cases. Cases and control subjects were
      similar with regard to age, sex, race, previous opportunistic infection, and use
      of antiretroviral therapy, but they were more likely than control subjects to
      have a history of intravenous drug use (49 versus 19%). The mean CD4+ counts were
      similar for cases and control subjects (154 versus 153 cells/microliters,
      respectively). The incidence rate of new AIDS-defining opportunistic infections
      in cases was 4.0 infections per 100 person-months compared with 2.8 infections
      per 100 person-months in control subjects for an incidence rate ratio (RR) of
      1.42 (95% confidence interval: 0.94-2.11). Cases also had a shorter overall
      survival than did controls subjects (p = 0.001). Active tuberculosis was
      associated with an increased risk for death (odds ratio = 2.17), even when
      controlling for age, intravenous drug use, previous opportunistic infection,
      baseline CD4+ count, and antiretroviral therapy. Although active tuberculosis may
      be an independent marker of advanced immunosuppression in HIV-infected patients,
      it may also act as a cofactor to accelerate the clinical course of HIV infection.

PMID- 7812543
TI  - The histology of allergic rhinitis and its comparison to cellular changes in
      nasal lavage.
AB  - To better understand how changes in cells in nasal secretions reflect changes in
      the nasal mucosa occurring during allergic reactions, we obtained nasal lavage
      and biopsy specimens from normal (n = 11) asymptomatic, seasonally allergic (n =
      18), and perennially allergic (n = 18) subjects. Initial baseline lavages showed
      that perennially, and seasonally allergic subjects, out of their allergy seasons,
      had significantly higher numbers of eosinophils (p < 0.01) and neutrophils (p <
      0.01) and total cell counts (p < 0.05) than normal subjects. Biopsy results
      showed that at baseline, seasonally allergic subjects had thicker mucosa (p <
      0.01), greater numbers of intraepithelial mononuclear cells and total cells (p <
      0.01), and greater numbers of subepithelial neutrophils (p < 0.001) than
      perennially allergic subjects. Twenty-four hours after antigen provocation, nasal
      lavage of allergic subjects showed an increase in the number of eosinophils (p <
      0.05). Seasonally allergic subjects also had significant increases in numbers of
      intraepithelial mononuclear cells (p < 0.05) and total cells (p < 0.01), and in
      subepithelial eosinophils (p < 0.001) and mononuclear cells (p < 0.05), which
      were localized to the side challenged. Despite an influx in eosinophils, the
      epithelial layer was not changed from baseline. The data provide evidence that
      nasal secretions and the nasal mucosa represent two distinct cellular
      compartments.

PMID- 7812544
TI  - Decreased tobacco-glycoprotein-induced lymphocyte proliferation in vitro in
      pulmonary eosinophilic granuloma.
AB  - Pulmonary eosinophilic granuloma is a disorder caused by localized collections of
      proliferating histiocytes in the lung. Little is known about its etiology except
      that the majority (58 to 97%) of patients are current or ex-smokers, making the
      potential etiologic role of tobacco products an important area for research.
      Tobacco glycoprotein (TGP) is a potent immunostimulator that has been isolated
      from cigarette smoke. TGP-specific lymphocyte proliferation, and cytokine
      production in vitro, were measured in three patients with pulmonary eosinophilic
      granuloma in remission and in three closely matched normal subjects with similar
      smoking histories. One patient with eosinophilic granuloma of bone and a matched
      control subject were also studied. Peripheral blood mononuclear cells were
      cultured with TGP, the recall antigen streptokinase (SK), and the mitogen
      concanavalin A (Con A). All three of the patients with pulmonary eosinophilic
      granuloma exhibited significant decreases in lymphocyte stimulation to TGP,
      despite normal responses to SK and Con A. In contrast, the response of the
      patient with eosinophilic granuloma of bone was higher than her matched control.
      The mean responses of the patients with pulmonary eosinophilic granuloma to TGP
      was significantly lower than the mean of nondiseased smokers or of normal
      nonsmokers. Twenty-four-hour culture supernatants were collected and assayed for
      cytokine levels (IL-1, IL-2, and IL-6). TGP-stimulated IL-2 production was
      significantly lower in the patients with pulmonary eosinophilic granuloma than in
      the normal subjects, confirming the reduced T-cell proliferative
      response.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7812545
TI  - von Willebrand factor antigen levels are not predictive for the adult respiratory
      distress syndrome.
AB  - In patients with nonpulmonary sepsis, von Willebrand factor antigen (vWF:Ag or
      Factor VIIR:Ag) levels have been reported to be predictive for the development of
      the adult respiratory distress syndrome (ARDS). We addressed the ability to
      generalize these results by measuring serial Factor vWF:Ag levels in 96 patients
      at risk for the development of ARDS. Patients with sepsis, pancreatitis,
      hypertransfusion, witnessed aspiration of gastric contents, abdominal trauma,
      chest trauma, and multiple fractures were studied. Sequential measurements were
      obtained at enrollment into the study (T = 0), and T = 6, 12, 24, and 48 h.
      Subjects were grouped into sepsis and nonsepsis categories and analyzed according
      to the following outcome definitions: ARDS and non-ARDS. The mean values for the
      sepsis and nonsepsis groups were elevated above normal at all time points. A
      statistically significant difference occurred in the mean vWF:Ag level for the
      ARDS and non-ARDS patients in the nonsepsis group at T = 0 (p = 0.05). To assess
      the clinical utility of these results, ROC (receiver operating characteristics)
      curves were plotted at T = 0, and optimal cutoff values of vWF:Ag were
      determined. In the sepsis group, the best value for vWF:Ag above which patients
      would actually develop ARDS was 399%, resulting in a 70% sensitivity and a 47%
      specificity. For the non-sepsis patients, the optimal value was 273%, yielding a
      sensitivity of 64% and a specificity of 52%. We conclude that measuring vWF:Ag
      levels are not helpful in predicting the progression to ARDS in multiple at-risk
      patients.

PMID- 7812546
TI  - T-cell receptor V gene expression in HLA-typed Japanese patients with pulmonary
      sarcoidosis.
AB  - The clinical features of sarcoidosis vary in different ethnic groups, suggesting
      that different genetic or environmental backgrounds influence the disease. In
      Scandinavian sarcoidosis patients, we have previously described a correlation
      between lung-accumulated CD4+ T cells expressing the T-cell receptor (TCR) V
      alpha 2.3 gene segment and a particular HLA type (DR3[17],DQ2). For purposes of
      comparison, we have in this study investigated TCR V gene usage and gamma delta
      TCR expression in CD4+ and CD8+ T cells in bronchoalveolar lavage (BAL) fluid and
      peripheral blood in an ethnically distinct and homogenous group of individuals
      consisting of Japanese sarcoidosis patients and healthy controls. We used a panel
      of 13 monoclonal antibodies (Mab) specific for different TCR V genes, which
      altogether stained approximately 50% of the T cells, and triple staining
      techniques with flow cytometry. The patients and controls were also HLA-typed.
      Our results show a high degree of expression of gamma delta TCR in peripheral
      blood T cells of close to half of the patients. Expansions of T-cell subsets were
      readily detected in the CD8+ T-cell population, while a more homogenous staining
      pattern was found in the CD4+ T-cell population. These findings show the
      importance of ethnic origin and environment in discussions of TCR V gene usage.

PMID- 7812548
TI  - Proinflammatory cytokines in hypersensitivity pneumonitis.
AB  - We examined the synthesis and release of the proinflammatory cytokines macrophage
      inflammatory protein-1 alpha (MIP-1 alpha) and interleukin-8 (IL-8) in the
      context of subjects with hypersensitivity pneumonitis (HP). Subjects with acute
      HP were found to have alveolar macrophages that released high levels of MIP-1
      alpha and IL-8, whereas control subjects had cells that released low levels of
      these factors. Bronchoalveolar lavage fluid from HP subjects contained low but
      significant levels of MIP-1 alpha and IL-8. Immunohistochemistry revealed that
      macrophages from acute HP subjects expressed MIP-1 alpha and IL-8 at high levels.
      Treatment of acute HP subjects by contact avoidance or by corticosteroids reduced
      the synthesis of both cytokines. Supernatants of alveolar macrophages from
      subjects with HP were shown to attract activated CD8+ T lymphocytes, and this
      activity was significantly inhibited by anti-MIP-1 alpha. MIP-1 alpha and IL-8
      may be important inflammatory cytokines in the development of HP via their
      capacity to attract inflammatory cells (activated CD8+ T lymphocytes and
      neutrophils, respectively) into the airways of subjects with HP.

PMID- 7812547
TI  - Alveolar hemorrhage. Diagnostic criteria and results in 194 immunocompromised
      hosts.
AB  - To establish the diagnosis of alveolar hemorrhage (AH) in cells recovered by
      bronchoalveolar lavage (BAL), Golde and colleagues created a score based on the
      hemosiderin content of alveolar macrophages stained with Prussian blue. We used
      an easier method, calculating the percentage of siderophages among the total
      alveolar macrophages recovered by BAL. We have retrospectively studied this
      method in 240 BALs performed in 194 immunocompromised patients. Prussian blue
      staining was performed on each BAL sample, and the Golde score was calculated for
      47 samples chosen at random. The methods were compared for diagnosing AH. The
      percentage of siderophages correlated well with the Golde score. AH was defined
      by at least 20% siderophages. This definition was validated by comparison with
      the method of Kahn and coworkers. AH was present in 87 (36%) of the samples and
      was significantly associated with four parameters: thrombocytopenia (<
      50,000/mm3), other abnormal coagulation parameters, renal failure (creatinine >
      or = 2.5 mg/dl), and a history of heavy smoking. The diagnosis of AH did not
      correlate with either the cause or the outcome of pneumonia. AH was seen more
      frequently in cardiac transplant patients (75%). In our experience, (1) a
      percentage of siderophages > or = 20% is sufficient and is an easier determinant
      of the diagnosis of AH than the Golde score; and (2) AH is rarely the sole cause
      of lung injury and is usually associated with other causes of pneumonia. AH may
      be considered more as a sign than as a distinct disease in this population.

PMID- 7812549
TI  - Latent adenoviral infection in follicular bronchiectasis.
AB  - The follicular form of bronchiectasis originally described by Whitwell (1) has
      been associated with adenoviral infection. The present study compares resected
      lungs from 16 patients with follicular bronchiectasis (in 10 of whom a nonviral
      etiology was identified) with those from eight patients with a nonfollicular
      histologic pattern. DNA isolated from sections of 45 paraffin-embedded lung
      samples was subjected to the polymerase chain reaction (PCR) using primers for
      the E1A region of the adenovirus genome and the human HLA DQ alpha gene. In situ
      hybridization (ISH) was performed on separate sections cut from the same blocks
      using a probe for the entire adenovirus 5 genome. E1A was demonstrated in six of
      eight patients (75%) with non-follicular bronchiectasis (non-FB) and in four of
      16 (25%) with follicular bronchiectasis (FB) (p < 0.03, Fisher's exact test). The
      optical density ratio for the E1A product of PCR (ratio of E1A product from
      specimen to that from 1 pg adenovirus DNA) was significantly lower in FB than in
      non-FB (0.057 +/- 0.054 versus 0.365 +/- 0.223 [mean +/- SEM], p < 0.05).
      Moreover, the duration of symptoms of bronchiectasis in patients without E1A in
      bronchial specimens was significantly shorter than that of patients with positive
      E1A PCR products (3.09 +/- 1.44 versus 14.41 +/- 3.33 yr; p < 0.05). By ISH,
      adenovirus was demonstrated in three patients with FB and in two with non-FB
      (17.2 and 18.8% of tissue blocks, respectively; NS).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7812550
TI  - Antibody to interleukin-5 inhibits virus-induced airway hyperresponsiveness to
      histamine in guinea pigs.
AB  - In humans, respiratory viral infections lead to increased airway responsiveness
      and exacerbations of asthma. In the present study, the role of interleukin-5 (IL
      5) in virus-induced airway hyperresponsiveness and inflammation was examined in
      guinea pigs. In animals treated with control antibody, parainfluenza-3 virus
      significantly potentiated (219%) the histamine-induced increase in lung
      resistance compared with vehicle treatment. In addition, viral infection
      significantly increased (130 to 450%) the responsiveness of isolated tracheal
      segments to histamine in animals treated with control antibody. In guinea pigs
      treated with control antibody, the numbers of eosinophils (226%), neutrophils
      (1,380%), and monocytes (626%) in bronchoalveolar lavage fluid were significantly
      increased after viral infection. The level of major basic protein in
      bronchoalveolar lavage fluid was not altered after viral infection. In addition,
      electron microscopic examination of eosinophils in airway tissue and alveolar
      lumen did not point to increased degranulation after viral infection. In guinea
      pigs treated with antibody to IL-5 the virus-induced airway hyperresponsiveness
      to histamine both in vivo and in vitro was almost completely inhibited. In guinea
      pigs treated with anti-IL-5, viral infection significantly increased the numbers
      of eosinophils (234%), neutrophils (1,255%), and monocytes (617%) in
      bronchoalveolar lavage fluid. These data suggest that IL-5 plays an important
      role in airway hyperresponsiveness to histamine but not in the infiltration of
      eosinophils after respiratory viral infection.

PMID- 7812551
TI  - Persistent airway hyperresponsiveness and histologic alterations after chronic
      antigen challenge in cats.
AB  - We studied the effect of chronic immune sensitization on the airway reactivity
      and associated cytologic and histologic alterations in initially nonatopic cats,
      a species that spontaneously develops idiopathic asthma. Seven cats were
      sensitized by intramuscular injection of Ascaris suum antigen (AA) for 4 wk, and
      four other cats served as sham controls. Airway sensitization was demonstrated by
      an increased response to nebulized AA in sensitized animals (RL = 45.9 +/- 6.1 cm
      H2O/L/s, versus a baseline response of 24.7 +/- 1.5 cm H2O/L/s, p < 0.01), and
      hyperresponsiveness was demonstrated by an increased response to acetylcholine
      (ACh)-challenge 24 h after AA (approximately 1.0 log decrease in PD200, p <
      0.01). The number of eosinophils in the sensitized animals' bronchoalveolar
      lavage (BAL) fluid increased 12-fold (p < 0.01 versus control) in response to AA
      challenge; 32 +/- 5% of the BAL eosinophils had a specific density < 1.050,
      versus 8 +/- 2% prior to AA challenge (p < 0.05). There was no change in airway
      reactivity, eosinophil recovery, or density in the control group 24 h after sham
      challenge with saline. The same seven sensitized cats further received nebulized
      AA three times weekly for 4 to 6 wk, after which BAL samples were again obtained
      and ACh dose-response curves generated 72 h after the final administration of
      nebulized AA. Airway hyperresponsiveness increased (approximately 1.5 log
      decrease in PD200, p < 0.001) and the number of eosinophils recovered in BAL
      fluid was increased 11-fold (p < 0.05). Necropsy specimens demonstrated
      bronchoconstriction in AA-challenged animals but not controls; luminal narrowing
      was accompanied by: (1) a 29.0 +/- 0.34% increase in smooth-muscle thickness (p <
      0.05); (2) goblet-cell and submucosal-gland hypertrophy and hyperplasia; and (3)
      epithelial erosion and eosinophilic infiltration. We demonstrate in nonhuman
      species persistent airway hyperreactivity associated with a complete
      constellation of histologic changes in epithelium, smooth muscle, and mucus
      glands, and cytologic changes in BAL fluid, all induced by immune sensitization.
      Our data suggest that chronic immune sensitization per se could be a salient
      factor in causing many of the changes associated with chronic bronchial asthma.

PMID- 7812552
TI  - Mandibular advancement splint: an appliance to treat snoring and obstructive
      sleep apnea.
AB  - Snoring and obstructive sleep apnea (OSA) are related to narrowing of the upper
      airway. A mandibular advancement splint (MAS) could improve both conditions by
      increasing oropharyngeal and hypopharyngeal dimensions. The effects of a MAS on
      snoring and OSA was evaluated 3.5 +/- 2.1 (mean +/- SD) mo after issue in 57
      subjects with habitual loud snoring, 39 of whom had an apnea-hypopnea index (AHI)
      > or = 10. Assessment was by questionnaire (all subjects) and polysomnography (51
      subjects, 47 male) including measurement of sound intensity. Use of the MAS was
      randomized to first or second half of study. Snores were scored where inspiratory
      noise was greater than 5 dB above background. Total sleep time, sleep efficiency,
      % REM sleep, and % sleep spent supine were similar (p > 0.05) with and without
      the MAS. Snores per sleep minute, corrected for time in apnea, and sound
      intensity of snores (% snores > or = 50 dB) decreased with the MAS from 11.0 +/-
      5.8 and 42.0 +/- 25.0% to 9.0 +/- 6.0 (p < 0.01) and 26.2 +/- 25.2% (p < 0.01),
      respectively. Using the MAS significantly improved OSA: AHI decreased from 32.2
      +/- 28.5 to 17.5 +/- 22.7 (p < 0.01) and arousal index decreased from 31.4 +/-
      20.6 to 19.0 +/- 14.6 (p < 0.01). AHI decreased to < 20 with the MAS in 12 of 17
      subjects where untreated AHI was between 20 and 60, and in 2 of 9 subjects where
      untreated AHI was > 60. Forty-five patients continued to use the MAS
      regularly.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7812553
TI  - Serologic monitoring of disease and treatment in a patient with pulmonary
      aspergilloma.
AB  - Disease progression and efficacy of fungistatic treatment in pulmonary
      aspergilloma (PA) are difficult to monitor. The usefulness of chest tomography,
      IgG-ELISA serology, double immunodiffusion, and IgG-immunoblotting was assessed
      in monitoring disease progression and efficacy of itraconazole treatment during a
      9-yr follow-up of a patient with two exacerbations of PA. A rise in IgG-ELISA
      titer coincided with a recrudescence of clinical symptoms, whereas a decrease
      after treatment paralleled clinical improvement. IgG-binding to a 32-kD serine
      protease and to 60- and 94-kD proteins produced with collagen-containing culture
      medium closely corresponded with IgG-ELISA titers. IgG-binding to a 40-kD
      metalloprotease remained at very low levels until symptoms and fungal growth
      became well advanced, when a sharp rise was seen. Responses to all antigens
      rapidly diminished after the start of successful treatment with itraconazole.
      Serology may be a useful adjunct in the monitoring of disease progression and the
      efficacy of itraconazole treatment in patients with PA. IgG-binding to individual
      fungal proteins shows subtle differences in kinetics. Immunologic responses to
      fungal proteases raised with collagen-containing culture media may reflect fungal
      proteolytic involvement during disease progression and treatment more closely
      than responses to proteins raised with conventional media.

PMID- 7812554
TI  - Restrictive pulmonary disease due to interlobular septal fibrosis associated with
      disseminated infection by Strongyloides stercoralis.
AB  - Strongyloidiasis is caused by the nematode Strongyloides stercoralis. The
      parasite has a unique life cycle that enables it to cause a hyperinfection
      syndrome in which pulmonary involvement is characteristic. We describe the case
      of a 68-yr-old Hispanic male from Puerto Rico with disseminated strongyloidiasis
      who developed intense granulomatous reaction in the lung associated with
      interlobular septal fibrosis. Granulomatous lung disease leading to fibrosis
      within the lung has been well demonstrated in schistosomiasis, another parasitic
      disease. This case represents the first report, as far as we are aware, of
      fibrosis within the lung and restrictive pulmonary disease in association with
      Strongyloides stercoralis.

PMID- 7812555
TI  - Fetal corticosteroid and T4 treatment effects on lung function of surfactant
      treated preterm lambs.
AB  - Three groups of sheep fetuses at 125 or 126 d gestational age randomly received a
      single ultrasound-guided intramuscular injection of saline, 0.5 mg/kg
      betamethasone, or 0.5 mg/kg betamethasone plus 50 micrograms/kg thyroxine (T4).
      Forty-eight hours later the fetuses were delivered, treated with a pulmonary
      surfactant preparation, and ventilated for 3 h. Corticosteroids alone and in
      combination with T4 increased FRC, compliance, and lung volumes, and decreased
      the protein leak into the airspace. Saturated phosphatidylcholine pool sizes
      recovered by alveolar washing were not changed after hormone treatment. To
      evaluate the function of surfactant recovered from the lambs in vivo, we treated
      preterm rabbits at 27 d gestational age with the large-aggregate surfactant from
      alveolar washes. Large-aggregate surfactants and the pulmonary surfactant
      preparation increased compliances and maximal lung volumes relative to those in
      untreated preterm rabbits. Large-aggregate surfactants improved compliance more
      than did the pulmonary surfactant preparation. We conclude that ultrasound-guided
      single fetal corticosteroid treatment followed by postnatal surfactant improved
      postnatal lung function in preterm lambs. Addition of T4 did not augment
      corticosteroid effects. The function of the exogenous surfactant was improved in
      premature lamb lungs independently of the fetal treatment modality.

PMID- 7812556
TI  - The effect of mechanical ventilation on oxygen consumption in critically ill
      patients.
AB  - We measured oxygen consumption (VO2) during spontaneous breathing with continuous
      positive airway pressure (CPAP), assist control ventilation (AC), and control
      ventilation during muscle relaxation (AC-MR) in eight patients undergoing
      resuscitation from cardiopulmonary failure. VO2 decreased in all eight patients
      between CPAP and AC-MR; mean VO2 (255 +/- 92 ml/min) on CPAP exceeded that on AC
      MR (209 +/- 79 ml/min) (p < 0.005). Compared with CPAP, AC without MR reduced VO2
      in five of eight patients and mean VO2 (227 +/- 59 ml/min) tended to decrease (p
      = 0.14); clinical examination did not distinguish patients requiring MR to reduce
      VO2 further. If VO2 on CPAP approximates VO2 during spontaneous breathing, the
      difference between CPAP and AC-MR (VO2resp) represents the decrement of VO2 that
      can be obtained during muscle rest. Both VO2resp and the mechanical work
      performed by the ventilator on the respiratory system were increased to about
      five times the efficiencies reported for normal patients, but VO2resp did not
      correlate with the mechanical work because of a wide range of respiratory muscle
      efficiencies. These efficiencies are less than those reported in normal patients,
      which may reflect the effect of sepsis, acidemia, hypoxia, or other conditions in
      these patients. We conclude that mechanical ventilation with muscle relaxation
      reduces VO2 by more than 20%; beyond stabilizing pulmonary gas exchange, these
      interventions preserve limited O2 delivery (QO2) for other vital organs.

PMID- 7812557
TI  - Reversal of sinus arrest and atrioventricular conduction block in patients with
      sleep apnea during nasal continuous positive airway pressure.
AB  - Sinus arrest and atrioventricular (AV) block have been demonstrated in as much as
      30% of patients with sleep apnea (SA). The reversal of heart block after
      tracheostomy has been shown. Nasal continuous positive airway pressure (nCPAP)
      now is widely used as the treatment of SA, but little data are available on the
      effect of nCPAP on heart block in patients with SA. During a 17-mo period 239
      patients were found to have SA in an ambulatory study. Heart block was identified
      in 17 (16 male, one female) of these patients. Standard polysomnography and two
      channel long-term ECG before and during nCPAP therapy were performed in order to
      assess the effect of nCPAP on SA and heart block. Mean age of the 17 patients was
      50.7 yr (range, 27 to 78 yr), mean respiratory disturbance index (RDI) was 90/h
      (SD +/- 36.1) before nCPAP and 6/h (SD +/- 6.2) on the second treatment night.
      The number of episodes of heart block during sleep decreased significantly (p <
      0.001) from 1,575 before therapy to 165 during nCPAP. In 12 patients (70.6%)
      heart block was totally prevented by nCPAP. In another three patients, there was
      a 71 to 97% reduction in the number of episodes of heart block on the second
      treatment night, and in two of them a complete reversal occurred thereafter. Two
      patients exhibited an increase in block frequency during nCPAP, which was
      reversed after 4 wk of nCPAP in one but persisted in the other.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7812558
TI  - The association of HLA-DR3 with specific IgE to inhaled acid anhydrides.
AB  - We have undertaken a case referent study of the association between HLA allele
      frequency and specific IgE antibody to acid anhydride-human serum albumin (AA
      HSA) conjugates among acid anhydride workers. Thirty cases with radio
      allergosorbent test score versus AA-HSA conjugates > 2 were compared with 30
      referents without specific IgE selected from the same factory sites as the cases
      and matched for age, sex, duration of exposure, atopic status, and smoking habit.
      We found a significant excess of HLA-DR3 in the cases with specific IgE to acid
      anhydrides when compared with the referents (50% versus 14%, Fisher's statistic =
      8.4; odds ratio = 6, p = 0.05 corrected). The excess of HLA-DR3 was particularly
      associated with IgE versus trimellitic anhydride, with HLA-DR3 present in eight
      of 11 workers with and in two of 14 referents without IgE (Fisher's statistic =
      8.5, odds ratio = 16, p = 0.004). The proportion of HLA-DR3 among the phthalic
      anhydride workers was not different in those with IgE (two of 12) from their
      referents (two of 14). These findings suggest MHC II proteins are an important
      determinant of the specificity of the IgE response to an inhaled hapten.

PMID- 7812559
TI  - Bronchodilator and bronchoprotective effects of cilostazol in humans in vivo.
AB  - Cilostazol is a selective orally active phosphodiesterase (PDE) III inhibitor.
      This study was conducted to evaluate whether inhibition of PDE subtype III can
      reduce bronchial responsiveness. We examined the effects of cilostazol on
      bronchial responsiveness to methacholine in eight normal subjects by a single
      blinded, crossover study. Each subject received 200 mg of cilostazol or placebo
      in random order. The subjects underwent methacholine challenge test 3 h after
      administration of each drug on two occasions separated by 5 d or more. The
      geometric mean value of provocative concentration of methacholine causing a 20%
      fall in FEV1 (PC20-FEV1) and the mean value (+/- SEM) of maximum expiratory flow
      on partial flow-volume curve at isovolume of 40% FVC above residual volume
      (PEF40) after administration of cilostazol were 25.3 (geometric standard error of
      the mean [GSEM], 1.35) mg/ml and 3.78 +/- 0.31 L/s, which were significantly (p <
      0.02 and p < 0.05) greater than those after the placebo administration (6.81
      [GSEM, 1.42] mg/ml and 2.71 +/- 0.39 L/s). All subjects complained of mild to
      severe headache when cilostazol was given. These findings suggest that PDE III
      inhibitors such as cilostazol have bronchodilator and bronchoprotective effects
      in humans. Further studies regarding smaller oral dosing of or aerosol
      administration of cilostazol or the other PDE III inhibitors are needed to
      determine clinical usefulness.

PMID- 7812560
TI  - Role of atrial natriuretic factor in lung physiology and pathology.

PMID- 7812561
TI  - NHLBI Task Force summary. Task Force on Research in Cardiopulmonary Dysfunction
      in Critical Care Medicine.
AB  - Research accomplishments during the past decade have led to a much greater
      understanding of molecular, cellular, and pathophysiological derangements
      occurring in the lung and other organ systems during critical illness. Despite
      this progress, care of critically ill patients with cardiopulmonary dysfunction
      remains a major health challenge. Expansion of research efforts is imperative and
      particularly opportune at this time because of exciting developments in
      understanding various mediators involved in inflammation and repair. Future
      advances in treating critical illness depend on basic understanding of the
      pathogenesis and pathophysiology of acute injury and repair. Key observations
      gained through clinical and epidemiological studies must be tested in the basic
      science laboratory. Increased and coordinated efforts in epidemiology, clinical,
      and basic research are essential for future progress.

PMID- 7812562
TI  - NHLBI Workshop summary. Stress and asthma.

PMID- 7812563
TI  - Changing physician-patient relationship.

PMID- 7812564
TI  - V/Q scan can quantitate right to left shunt.

PMID- 7812565
TI  - Increased Pneumocystis carinii recovery from upper lobes in Pneumocystis
      pneumonia.

PMID- 7812566
TI  - Breathing comfort during weaning with two ventilatory modes.

PMID- 7812567
TI  - Randomized clinical trial of pressure-controlled inverse ration ventilation and
      extra corporeal CO2 removal for ARDS.

PMID- 7812568
TI  - Effect of photochemical air pollution on acute respiratory symptoms in children.
AB  - In the spring and summer of 1989, an epidemiologic study of the acute effects of
      photochemical air pollution on the respiratory health of 300 children 7 to 11 yr
      old was conducted. The children studied were a general population sample of the
      children living in two rural towns in the Netherlands. For these children, small
      pulmonary function decrements associated with ambient ozone concentrations were
      reported previously. In this paper, the association between photochemical ambient
      air pollution and acute respiratory symptoms is evaluated. Occurrence of acute
      respiratory symptoms was registered by the parents of the children in a diary on
      a daily basis. The association of symptom prevalence and incidence with air
      pollution was evaluated using a logistic regression model that took auto
      correlation of the residuals into account. Several photochemical episodes
      occurred in the study period of 102 d. Hourly maximum ozone concentrations ranged
      from 14 to 114 ppb. Daily average PM10 concentrations ranged from 11 to 136
      micrograms/m3. Levels of acid aerosol were low. No associations of daily symptom
      prevalence or incidence with same-day or previous day concentration levels of
      ozone, PM10, fine particle sulfate, or nitrate were observed.

PMID- 7812569
TI  - Response to acute ozone exposure in healthy men. Results of a screening
      procedure.
AB  - We screened 64 healthy, nonsmoking men, 18 to 35 yr old, for their sensitivity to
      0.35 ppm ozone (O3) administered for 130 to 150 min with intermittent exercise.
      The changes in FVC, FEV1, AND FEF25-75 (p < 0.0001) immediately after O3 exposure
      varied widely among subjects. Histograms of the percentage changes in FVC and
      FEV1 did not differ from a unimodal, skewed (gamma) distribution (p = 0.99 and p
      = 0.17, respectively); the changes in FEF25-75 tended to deviate from a gamma
      distribution (p = 0.055). To adjust FEF25-75 for the confounding effects of O3 on
      FVC, we used multiple linear regression analysis with contemporaneous FVC as a
      covariable, analysis of a subgroup of nine subjects whose O3-induced FVC changes
      were < or = 5%, and volume correction of FEF25-75 for any changes in FVC after
      exposure. These analyses showed reductions in FEF25-75 unexplained by and
      following a different time course than the O3-induced changes in FVC. In 26
      subjects also exposed to filtered air, significant effects of O3 on respiratory
      frequency (p < 0.004) and tidal volume (p < 0.0007) correlated weakly with FVC
      changes. The results confirm the wide variability in spirometric responsiveness
      among individuals to O3 and suggest that intrinsic narrowing of the small airways
      may be a significant component of the functional response.

PMID- 7812570
TI  - Exposure-response relationship between passive smoking and adult pulmonary
      function.
AB  - The effects of exposure to environmental tobacco smoke (ETS) on pulmonary
      function were investigated in a random sample of 1,033 adults aged 40 to 69 yr
      from a residential area in Beijing. Compared with those not exposed, those
      exposed to ETS either at home or at work were associated with a 102-ml (SE = 40
      ml) reduction in FEV1 and a 151-ml (SE = 44 ml) reduction in FVC after adjustment
      for confounding factors. Home and work ETS exposure was respectively associated
      with a 102-ml (SE = 33 ml) and 61-ml (SE = 34 ml) reduction in FEV1. When the
      subjects were grouped into three exposure categories (none, home only or work
      only, and both), the deficits in FEV1 and FVC in the third category were the
      greatest and statistically significant. The adverse effects of ETS were
      consistently observed in stratified analyses according to sex, occupational
      exposure, indoor use of coal stoves, and education. When ETS exposure was
      measured by the cigarettes smoked by other household members at home per day, an
      exposure-response association with FEV1 and FVC was again statistically
      significant. In conclusion, this study demonstrated that there is a significant
      association between exposure to ETS and reduced levels of FEV1 and FVC in adults,
      and such an association is dose-dependent.

PMID- 7812571
TI  - Determinants of longitudinal changes in spirometric function among swine
      confinement operators and farmers.
AB  - To assess whether working in a swine confinement facility causes an excess or
      accelerated decline in lung function, we conducted a population-based study to
      evaluate the determinants of longitudinal changes in airflow in a population of
      swine confinement operators. Spirometric measures of lung function were compared
      between swine confinement operators (N = 168) and neighborhood farmer control
      subjects (N = 127). Study subjects were randomly selected from a cohort of swine
      confinement operators in eastern Iowa. The control farming population was matched
      by geographic location, age, and sex to the swine confinement operators. On
      average, the follow-up time was approximately 2 yr, with a range of follow-up
      between 56 and 1,900 d. Although swine confinement operators and neighborhood
      farmers had similar demographic characteristics (age, gender, racial background,
      smoking history, and atopy status), swine confinement operators tended to have
      less farming experience and were more extensively followed (more measures of lung
      function and longer periods of observation) than the neighborhood farmer control
      group. Swine confinement operators were also exposed to higher environmental dust
      concentrations and other irritants than the farmer control subjects.
      Interestingly, the cross-sectional data indicated that swine confinement
      operators tended to have slightly lower measures of airflow and greater workshift
      declines in forced expiratory volume in one second (FEV1), forced vital capacity
      (FVC), and mid-expiratory flow (FEF25-75) than the neighborhood farmer control
      group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7812572
TI  - Prevalence of occupational asthma due to latex among hospital personnel.
AB  - Latex has been documented as causing immediate hypersensitivity reactions ranging
      from contact urticaria to severe anaphylaxis. Latex proteins may also act as
      airborne allergens causing rhinitis and asthma. The prevalence of occupational
      asthma due to latex gloves among health care workers is unknown. We surveyed the
      employees of a primary care hospital including nurses (n = 201), members of the
      cleaning staff (n = 50), and laboratory technologists (n = 38). In the initial
      part of the study, a questionnaire and skin-prick tests with latex and common
      inhalant allergens were administered to 273 of 289 (94%) members of the target
      population. Thirteen of the 273 subjects (4.7%; 95% CI: 2.6 to 8.1%) showed skin
      reactivity to latex. All latex-sensitive subjects reported glove-related
      urticaria, which was associated with rhinoconjunctivitis in 12 subjects and
      asthma in five subjects. No subject had a history suggestive of occupational
      asthma among those who had negative skin tests to latex. In the second part of
      the study, a histamine inhalation challenge was performed on 12 of 13 latex
      sensitive subjects, including the five subjects with a history of occupational
      asthma. These 12 subjects demonstrated significant bronchial hyperresponsiveness.
      All underwent specific inhalation challenges with latex gloves in the laboratory.
      Seven subjects developed a significant bronchial response (four immediate and
      three dual reactions) to latex glove exposure. We conclude that occupational
      asthma due to latex occurred in 2.5% (95% CI: 1.0 to 5.2%) of hospital employees.
      Widespread use of latex gloves should therefore be considered a significant risk
      to the respiratory health of hospital employees.

PMID- 7812573
TI  - Changes in dyspnea, health status, and lung function in chronic airway disease.
AB  - The purpose of this study was to examine longitudinal changes in clinical
      parameters in patients with chronic obstructive pulmonary disease (COPD). We
      postulated that progressive dyspnea and decline in lung function over time would
      influence or impact patient's health status. Clinical ratings of dyspnea, general
      health status, and physiologic lung function were measured every 6 mo over a 2-yr
      period in an original group of 110 male patients with stable but symptomatic COPD
      and no significant comorbidity. At enrollment, age was 67 +/- 8 yr (mean +/- SD),
      forced expiratory volume in one second (FEV1) was 1.28 +/- 0.59 I (44 +/- 17% of
      predicted), and forced vital capacity (FVC) was 2.84 +/- 0.84 I (68 +/- 18% of
      predicted). A total of 34 patients "dropped out" because of death (n = 20),
      relocation (n = 7), and other reasons (n = 7). Dyspnea was measured using the
      transition dyspnea index (TDI), which represented changes from the baseline
      state; general health status was measured using the Medical Outcomes Study (MOS)
      20-item short-form survey; physiologic lung function was assessed by spirometry
      (FVC and FEV1) and inspiratory muscle strength (PImax). Statistical analyses were
      performed using all available data for each patient, including results until the
      time at which patients died or were lost to follow-up.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7812574
TI  - Quality of life in asthma clinical trials: comparison of salmeterol and
      salbutamol.
AB  - Most clinical trials in asthma have focused on outcomes that are primarily of
      importance to the clinician. Very few have assessed whether patients feel better
      and can function better in day-to-day activities. The aim of this study was to
      compare the effects of salmeterol (50 micrograms twice daily), salbutamol (200
      micrograms four times a day), and placebo on asthma-specific quality of life and
      to relate the findings to conventional clinical asthma outcomes. The study was a
      12-wk multicenter, double blind, randomized, placebo-controlled crossover trial
      with each trial medication taken for 4 wk. The subjects were 140 adults with mild
      to moderate asthma enrolled from 14 respiratory clinics across Canada. Outcome
      measures were: (1) the Asthma Quality of Life Questionnaire and spirometry at the
      end of each treatment period; and (2) daily asthma symptoms, morning and evening
      peak expiratory flow rates (PEFRs), and rescue salbutamol use during the last 14
      d of each treatment period. Asthma-specific quality of life, both overall and for
      the individual domains (activity limitation, symptoms, emotional function, and
      exposure to environmental stimuli) was better with salmeterol than with placebo
      (p < 0.0001), and better with salmeterol than with salbutamol (p < 0.001). In
      both comparisons, differences were not only statistically significant, but most
      were also clinically important. There were moderate correlations between change
      in quality of life and change in clinical outcomes.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7812575
TI  - Environmental and bronchoalveolar lavage Dermatophagoides pteronyssinus antigen
      levels in atopic asthmatics.
AB  - Overnight environmental home exposure to Dermatophagoides pteronyssinus in IgE
      sensitized individuals is often clinically associated with increased morning
      symptoms of rhinitis and/or asthma. We have investigated whether household
      exposure to D. pteronyssinus is associated with the presence of immunoreactive D.
      pteronyssinus I antigen (Der p I) in bronchoalveolar lavage (BAL) fluid in nine
      atopic asthmatics sensitized to D. pteronyssinus. Significant environmental
      concentrations of D. pteronyssinus were noted by light microscopy and immunoassay
      in the subjects' bedroom carpets (13.4 +/- 3.8 micrograms immunoreactive Der p
      I/g dust), mattresses (27.3 +/- 7.2 micrograms immunoreactive Der p I/g dust),
      and living room carpets (5.9 +/- 1.5 micrograms immunoreactive Der p I/g dust).
      Immunoreactive Der p I was measurable in 20-fold concentrated BAL fluids (3.4 +/-
      1.0 ng/ml concentrated BAL fluid) after overnight home exposure. A 24-h
      hospitalization in a D. pteronyssinus controlled environment (< 0.02 micrograms
      Der p I/g dust) resulted in a significant decrease in BAL Der p I concentrations
      (0.8 +/- 0.6 ng/ml). In vivo studies in nine asthmatics challenged
      endobronchially with D. pteronyssinus (5-60 ng Der p I) induced significant
      airway eosinophilia. These studies demonstrate that environmental exposure to
      microgram amounts of D. pteronyssinus is associated with airway recovery of small
      nanogram amounts of Der p I.

PMID- 7812576
TI  - Lymphocyte and macrophage activation in bronchoalveolar lavage fluid in nocturnal
      asthma.
AB  - Increased nocturnal airway narrowing is thought to occur as a consequence of an
      intensification of inflammatory processes at night. Lymphocyte and alveolar
      macrophage (AM) activation are thought to be associated with the clinical
      expression of asthma, and may be important in the occurrence of nocturnal asthma
      as well. The expression of CD25 and HLA-DR receptors on lymphocytes from
      bronchoalveolar lavage (BAL) and peripheral blood (PB) CD4+, as well as of CD14,
      IgG Fc, and CD11/CD18 leukocyte adhesion receptors on AM in BAL fluid and
      monocytes in PB, were determined at 16.00 and 04.00 h by flow cytometry. Their
      relationship with the occurrence of nocturnal asthma was investigated in eight
      nonatopic controls (Group 1) and 17 atopic asthmatic subjects, prospectively
      assigned to groups with a mean circadian peak expiratory flow (PEF) variation <
      15% (Group 2) and > or = 15% (Group 3). The occurrence of an increased circadian
      variation in PEF in asthmatic subjects was on the whole not associated with a day
      night fluctuation in lymphocyte numbers and subsets in PB or BAL fluid, nor with
      day-night changes in receptor expression on AM from BAL or monocytes from PB. The
      only exception was the presence of a greater day-night change in the proportion
      of HLA-DR-expressing CD4+ lymphocytes in the BAL fluid along with an increasing
      circadian PEF rhythm in asthmatic subjects (r = 0.68, p = 0.03). A further
      finding was that a lower number of BAL CD4+ lymphocytes at daytime was
      significantly related to a higher circadian PEF variation in asthmatic subjects
      (r = -0.66, p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7812577
TI  - Association of chronic obstructive pulmonary disease and sleep apnea syndrome.
AB  - The association of chronic obstructive pulmonary disease (COPD) and sleep apnea
      syndrome (SAS), which are both frequent diseases, is likely to occur in a number
      of patients. We have prospectively investigated a large series (n = 265) of
      patients who were selected solely on the basis of a confirmed diagnosis of SAS
      (apnea + hypopnea index > 20/hr). An obstructive spirographic pattern, defined by
      an FEV1/VC ratio < or = 60%, was observed in 30 of 265 patients (11%). These
      patients (subgroup "overlap") were older (58 +/- 9) versus 53 +/- 10 yr, p =
      0.01) than the remainder of the study population, and all were male patients.
      Body mass index (BMI) was identical in overlap patients to that in the remainder.
      Vital capacity and FEV1 were lower, by definition, in the overlap group. PaO2 was
      lower (66 +/- 10 versus 74 +/- 10 mm Hg, p < 0.001) and PaCO2 higher (42 +/- 6
      versus 38 +/- 4 mm Hg, p < 0.001) in the overlap group. Hypoxemia (Pao2, < or =
      65 mm Hg) was observed in 17 of 30 overlap patients and in 54 of 235 of the
      remainder. Hypercapnia (Paco2 > or = 45 mm Hg) was observed in 8 of 30 overlap
      patients and in 19 of 235 of the remainder. The pulmonary artery mean pressure
      (PAP) was higher in overlap patients both at rest (20 +/- 6 versus 15 +/- 5 mm
      Hg, p < 0.01) and during steady-state exercise (37 +/- 12 versus 29 +/- 10 mm Hg,
      p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7812578
TI  - Central apnea index decreases after prolonged treatment with acetazolamide.
AB  - Only a limited number of studies dealing with the epidemiology and therapy of
      central sleep apnea syndrome (CA) are available. The treatment strategies are
      poorly defined and not well evaluated. The aim of our present study was to treat
      selected CA patients with low dose acetazolamide (ACET) for a longer time period
      than has been done before. Previous studies were performed with high dose ACET
      provoking severe metabolic acidosis, not for more than 1 wk or only in
      obstructive apnea patients. Referred patients with suspicion of sleep-related
      breathing disorders (SRBD) were included in the study if, after a first selection
      night, their central apnea index (CAI) was > 5 or their apnea-hypopnea index
      (AHI) > 10 and their obstructive apnea index (OAI) < 5. Of 327 screened patients,
      14 (4.3%) fulfilled these criteria. Patients were then treated with ACET (250 mg,
      1 h before sleep): Polysomnography was repeated once after one single dose (N2)
      and twice after 1-mo chronic treatment without (N3) and with (N4) additional ACET
      administration. After each study night, arterial blood gases and chemical drive
      were measured. CAI (25.5 +/- 6.8 at N1) already decreased during N2 (13.8 +/-
      5.2) and further during N3 (6.6 +/- 2.9) and N4 (6.8 +/- 2.8) p < 0.01). OAI
      remained unchanged. Total sleep time (TST) and sleep efficiency index (SEI) did
      not change significantly. The number of arousals decreased from 62 +/- 11 at N1
      to 40 +/- 5 at N3 (p = 0.019).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7812579
TI  - Treatment of congestive heart failure and Cheyne-Stokes respiration during sleep
      by continuous positive airway pressure.
AB  - A previous uncontrolled study suggested that nasal continuous positive airway
      positive airway pressure (NCPAP) may improve left ventricular ejection fraction
      (LVEF) in patients with congestive heart failure (CHF) and Cheyne-Stokes
      respiration with central sleep apnea (CSR-CSA). In order to more critically
      evaluate the effects of NCPAP on cardiac function, we undertook a randomized,
      controlled trial of NCPAP in 29 patients with heart failure and CSR-CSA over a 3
      mo period, with LVEF as the primary outcome measure. Patients with CHF and
      associated CSR-CSA who were receiving optimal medical therapy were randomly
      assigned to a control group (n = 15) or a group receiving nightly NCPAP (n = 14).
      Twelve patients in each group completed the study. There was a greater
      improvement of LVEF in the NCPAP group than in the control group during the study
      (mean +/- SEM = 7.7 +/- 2.5 versus - 0.5 +/- 1.5%, p = 0.019). In addition, there
      was a significantly greater reduction in the number of apneas and hypopneas (
      28.5 +/- 3.9 versus -6.1 +/- 7.0 per hour of sleep, p = 0.012) in the NCPAP group
      than in the control group. Significantly greater improvements in symptoms of
      fatigue (5.6 +/- 1.2 versus 0.8 +/- 0.7, p = 0.005) and disease mastery (3.6 +/-
      1.1 versus -0.7 +/- 0.7, p = 0.031) were also observed in the NCPAP group. We
      conclude that in patients with chronic heart failure and CSR-CSA, nightly
      administration of NCPAP can attenuate CSR-CSA, improve cardiac function, and
      alleviate symptoms of heart failure.

PMID- 7812580
TI  - Determination of gas exchange threshold by nonparametric regression.
AB  - The gas exchange threshold (GET) has been used an an index of anaerobic threshold
      because it can be measured noninvasively. GET is estimated from a breakpoint in
      breath by breath values of carbon dioxide uptake (Vco2) and oxygen uptake (Vo2)
      obtained during a progressive exercise test. Three methods of estimating GET were
      evaluated: (1) the original V slope method (OVS) using two adjoining standard
      linear regressions, (2) the modified V slope method (MVS) where the breakpoint is
      detected by visual inspection, and (3) a new method that we developed with
      nonparametric regression (NPM) using cubic splines. Simulated data were used
      because the existence of a breakpoint is known with certainty. Detection accuracy
      for OVS and MVS never exceeded 63% because of a low specificity. The detection
      accuracy of NPM ranged between 50 and 89% depending on the amount of noise and
      abruptness of the threshold, and exceeded that of OVS and MVS at low levels of
      noise. NPM was significantly more accurate (p < 0.05) than OVS and MVS for
      detecting GET except with high levels of noise. Both NPM and OVS have similar
      degrees of numerical accuracy and are superior to the currently used MVS method
      in this respect. All three methods gave similar results on 20 exercise tests. We
      conclude from the simulated data that NPM is more accurate than OVS and MVS at
      detecting GET. NPM can be applied to human data and it provides results that are
      consistent with OVS and MVS.

PMID- 7812581
TI  - Sacral ulcers following cardiac surgery: incidence and risks.
AB  - This study examined the incidence and risk factors that relate to the development
      of sacral pressure ulcers following elective cardiac surgery. Perioperative
      variables were assessed using 136 adult patients. Ulcers, including 16 Stage I
      and 21 Stage II-III, occurred on 27.2% (n = 37) of the patients. Factors such as
      older age, transfer from another hospital, and a history of diabetes, were
      associated with ulcer development. These findings may be used to identify
      patients at risk for pressure ulcers during cardiac surgery.

PMID- 7812582
TI  - Pressure relief devices, risk factors, and development of pressure ulcers in
      elderly patients with limited mobility.
AB  - This study investigated the relationship among the use of pressure
      relieving/reducing support surfaces, risk factors, and the development of
      pressure ulcers in 108 hospitalized, elderly patients with limited mobility.
      Pressure ulcers developed in 27 of the patients, even though the majority of
      these (96%) had used a pressure-relieving/reducing support surface. On the other
      hand, many patients with mobility problems, fecal incontinence, decreased serum
      albumin levels, and decreased total protein levels did not develop pressure
      ulcers.

PMID- 7812583
TI  - Portrait of practice: healing heel ulcers.
AB  - Two treatments for heel pressure ulcers--a dressing foot wrap and a laminated
      foam boot (Lunax, BIO-SONICS)--were compared for effectiveness in a sample of 25
      Intensive Care Unit patients at a community teaching hospital. At the first sign
      of heel redness, 11 patients were assigned to receive a dressing foot wrap, and
      14 were assigned to wear a laminated foam boot on their heels. Subjects heel
      breakdowns were monitored every three days until one of the following conditions
      occurred: break of a blister, discharge from hospital, or death. None of the
      subjects receiving the dressing foot wrap showed improvement, whereas all but one
      of the subjects using the boot showed improvement.

PMID- 7812584
TI  - Pressure ulcers: quality management, prevalence, and severity in a long-term care
      setting.
AB  - The entire resident population of a long-term care (LTC) facility was followed
      for four years. Protocols for quality management reduced the prevalence rate of
      pressure ulcers from 7% in 1988 to 4% in 1992. The average percentage of
      residents who developed pressure ulcers in the LTC setting was 3.4% while 20% of
      the residents admitted from the acute care setting had pressure ulcers. Chi
      square statistics showed that the pressure ulcers originating in the acute care
      setting tended to be much more severe than pressure ulcers that developed in the
      LTC setting. The majority (59.7%) of pressure ulcers that developed in the acute
      care setting were stage III or stage IV. The majority (87%) of pressure ulcers
      that developed in the LTC setting were Stage I or II.

PMID- 7812585
TI  - Clinical educator and resource.

PMID- 7812586
TI  - [Zona pellucida antibody detection using the passive hemagglutination reaction.
      II. Clinical part].
AB  - The authors examined sera of patients suffering from idiopathic infertility,
      unsuccessful IVF, the diagnosis of habitual abortion and endometriosis, using the
      test of the passive haemagglutination reaction with sheep erythrocytes sensitized
      by 11 antigenic fractions of pig zona pellucida, molecular weights from 13.3-114
      kilodaltons. The authors analyze the assembled results with regard to individual
      antigenic fractions and with regard to the diagnoses. The frequency of positive
      reactions in patients is investigated in particular in the area of higher
      molecular weights, as compared with the control group of healthy fertile women.

PMID- 7812587
TI  - [Antiphospholipid antibodies in women with reproductive disorders].
AB  - The authors examined in serum of 121 women, using the ELISA method,
      anticardiolipine antibodies (ACA) class IgG and IgM. The examined women were
      divided into a group of women with a normal pregnancy (n = 14), a group of women
      with imminent abortion during the first trimester (n = 10) and a group of women
      treated for prolonged periods on account of sterility (n = 97). In women with a
      normal pregnancy only in one a positive titre in the IgG class was recorded. In
      the group with imminent abortion a positive ACA titre was found in three patients
      (30%); in women with negative results of the ACA examination, pregnancy
      continued. In sterile women positive ACA tests were recorded in 14.5%.

PMID- 7812588
TI  - [Hormonal therapy of osteoporosis in women after ovariectomy].
AB  - In 25 women with ovariectomy made before the menopause and in a control group of
      11 women after the menopause the authors examined laboratory values of the
      calcium phosphate metabolism and bone density. They repeated the examinations 6
      and 12 months after treatment with a combined sequence oestrogen and gestagen
      preparation--Presomen 0.6 comb. of KaliChemie (Solvay), FRG. After one year of
      treatment the calcium and phosphate blood levels did not change substantially nor
      the alkaline phosphatase activity or its bone isoenzyme (although an
      insignificant increase occurred after six months). On the other hand, the
      originally elevated calciuria suggesting enhanced resorption of bone mineral,
      declined in the group of ovariectomized women on average by 3.02 mmol/d, i.e. the
      women lost by 120 mg less Ca, and the density increased by 6.80%! In a group of
      postmenopausal women the calciuria declined on average by 2.80 mmol (urinary Ca
      losses were by 113 mg lower) and the density increased by 4.18%. The results of
      this investigation support unequivocally not only the benefit but also the
      necessity of combined hormonal treatment after ovariectomy made before the
      menopause and provide also evidence of its importance in the prevention of
      osteoporosis in postmenopausal women.

PMID- 7812589
TI  - [Hysteroscopic sterilization using Ovabloc].
AB  - The authors give an account on 29 sterilizations made by the hysteroscopic route,
      using the preparation OVABLOC. It is a reversible block of the oviducts by
      occlusive material. Under hysteroscopic control into the inner orifice of the
      oviduct by means of a special injecting device under pressure a two-component
      mixture of silicone and a catalyst is instilled which causes within 5 min.
      hardening of the mass and the formation of an elastic relief filling of the
      entire oviduct. In 25 of the women (86.2%) the procedure was accomplished without
      complication, in the 3 (10.3%) the procedure failed on account of technical
      difficulties and in one case (3.5%) during hysteroscopy the uterine wall was
      perforated. On X-ray check-up after three months of 25 successfully operated
      women in 24 the position of the tubal occlusion was unaltered (the material is
      due to dispersed silver particles contrasting on X-ray); in one case it was
      loosened. The advantages of the method are that it is sparing, well tolerated and
      easily reversible, the disadvantage is that it is relatively laborious and
      expensive.

PMID- 7812590
TI  - [Klimonorm and precanceroses of the endometrium].
AB  - In the prospective study the authors administered for one year the preparation
      Klimonorm (Jenapharm) to 90 women divided into three groups. Of 90 patients at
      the onset 30 women suffered from precancerous endometriosis confirmed by
      histological and cytological examination. The remaining 60--half with and half
      without menstrual bleeding--all had climacteric complaints. The authors evaluated
      by statistical methods various parameters, in particular Kuppermann's index, the
      thickness of the endometrial mucosa in the uterine cavity by ultrasound, the
      oncological endometrial cytology by a cytobrush and subsequent lavage of the
      uterine cavity during 4 check-up examinations after three-month intervals. At the
      onset of the investigation and after one year the hormonal serum levels (FSH, LH,
      17-beta oestradiol) were assessed and in the patients with precancerous
      conditions also the histology of the endometrium. The results are promising, in
      particular the significant drop of Kuppermann's index already after three months
      to one third of the baseline value in all three groups of patients; complete
      reversal to the negative side as regards the cytological finding on the
      endometrium, correlating with the histological finding; unaltered body weight;
      change of the thickness of the endometrium in the group of precanceroses to more
      favourable values. Based on these results the authors hold the view that hormonal
      therapy (oestrogen-gestagen) in the climacteric and in endometrial precanceroses
      is fully justified. Klimonorm (Jenapharm) proved a very useful preparation as the
      patients' subjective complaints improved and also with regard to the favourable
      effect on endometrial precanceroses which can be monitored without active
      abrasion only by a cytobrush.

PMID- 7812591
TI  - [The early androgen syndrome--effect on the hormonal and immune system].
AB  - Administration of 1 mg testosterone propionate to neonate mice of both sexes on
      the 4th day after birth causes marked and prolonged changes in some parameters of
      the immune and hormonal system. At the age of one month the oestradiol level in
      males and females is markedly elevated, but not the testosterone level. There is
      a marked increase in the metabolic activity of peritoneal macrophages stimulated
      by zymosan and at the same time also in the percentage of cells phagocytizing
      inert HEMA particles. There was a marked increase in the amount of haemoglobin in
      females and of the bone marrow cellularity (in particular in males). Obviously
      also changes in cell differentiation occur, the ratio of different cell types in
      the peripheral blood stream changes. There is a decline of neutrophil
      granulocytes with a divided nucleus (in particular in males, where also the
      number of lymphocytes rises). The cell-mediated immune response is also altered
      as the graft response to the host is more intense. The humoral immunity against T
      dependent antigen is also affected. The titre of IgG antibodies is reduced and
      the titre of IgM antibodies elevated. The results are discussed, but so far it is
      difficult to decide whether the observed changes of the immune system are
      primary, i.e. directly induced by testosterone, or whether they are secondary,
      i.e. induced by an elevated testosterone level.

PMID- 7812592
TI  - [Short-term variability of fetal cardiac activity in 1F and 2F behavioral
      states].
AB  - The investigation revealed intraindividual differences in characteristics of the
      short-term variability of cardiac action of normal foetus during the tenth month
      of pregnancy in the phase of behavioural state 1F and 2F. These conditions, in
      particular state 1F, are otherwise frequently the cause of false positivity of
      the non-stress test during antepartum monitoring because the values of the
      parameter of short-term variability of FHR when reading the hard print of the
      cardiotocogram can permit also an interpretation suggesting the diagnosis of
      chronic foetal hypoxia. Simultaneously the authors proposed and tested a simple
      supplementing device which makes it possible to evaluate continuously selected
      parameters of the short-term variability of cardiac action for the needs of
      antepartum monitoring.

PMID- 7812593
TI  - [Complications in insulin-dependent diabetic mothers during pregnancy and the
      long-term prognosis for their children].
AB  - The authors investigated whether vascular complications of insulin-dependent
      diabetic pregnant women can influence on a long-term basis their children in
      adult life. In a group of 169 children of diabetic mothers (CDM) 12 developed
      diabetes during childhood and adolescence; in the remaining 157, age 20.75 +/-
      0.31 (SE) the following tests were made: oral glucose tolerance test (OGTT),
      insulin level, parameters of the lipid metabolism, and blood pressure was
      assessed. CDM were divided into three groups: 1. CDM whose mothers had diabetic
      complications; according to White's classification of diabetes during pregnancy
      they belonged into class D and F (n = 10). 2. CDM whose mothers were classified
      with regard to diabetes during pregnancy as class B and C with subsequent
      toxaemia of pregnancy (n = 27), 3. CDM of mothers class B and C without toxaemia
      of pregnancy (n = 117). All investigated groups of CDM had significantly higher
      sums of blood sugar and insulin levels during the OGTT (P < 0.01), as compared
      with the control group (n = 31). In the first group of CDM the values were
      significantly higher than in the third group of CDM. As to cholesterol and
      triacylglycerol levels, the differences were not significant, the non-esterified
      fatty acid levels were higher in the second group than in controls (P < 0.05). In
      the first two groups also a higher systolic pressure was recorded than in
      controls (P < 0.01). Two children of the first group, two children of the second
      group and eight children of the third group of CDM developed diabetes.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7812594
TI  - [Secular trends in a decreased sperm count in the ejaculate in man].

PMID- 7812595
TI  - [Hyperprolactinemia and idiopathic sterility].

PMID- 7812596
TI  - [On the article by J. Zach, et al: Chorioamnionitis and neonatal infection].

PMID- 7812597
TI  - [The 14th Prague Gynecology Seminar organized by the Gynecology Section of the
      Czech Oncologic Society held December 1993--selected reports].

PMID- 7812598
TI  - Characterization of the 5-HT receptor potentiating neuromuscular cholinergic
      transmission in strips of human isolated detrusor muscle.
AB  - In human isolated detrusor strips, submaximal contractile responses evoked by
      electrical stimulation were resistant to hexamethonium (30 microM) and abolished
      by tetrodotoxin (0.6 microM) and hyoscine (1 microM), indicating the activation
      of postganglionic cholinergic nerves. In methysergide (1 microM) and ondansetron
      (3 microM) pretreated tissues, 5-hydroxytryptamine (5-HT) (0.3 nM-1 microM)
      caused a concentration-dependent increase in the amplitude of contractions (pEC50
      = 8.1), which was antagonized by the selective 5-HT4 receptor antagonist GR
      113808 (3, 10 and 30 nM) in a competitive manner. Schild analysis yielded a pA2
      estimate of 8.9, a value comparable to that reported for GR 113808 in other
      animal and human peripheral tissues (8.8-9.7). Our findings indicate that
      neuromuscular cholinergic transmission in human isolated detrusor muscle is
      facilitated by neural 5-HT receptors belonging to the 5-HT4 subtype. The human
      urinary bladder can thus be regarded as an additional site in which 5-HT4
      receptors are distributed.

PMID- 7812599
TI  - Role of intrathecal tachykinins for micturition in unanaesthetized rats with and
      without bladder outlet obstruction.
AB  - 1. The effects on micturition of RP 67,580, a selective NK1 receptor antagonist,
      and SR 48,968, a highly, potent antagonist at NK2 receptor sites, given
      intrathecally (i.t.) or intra-arterially (i.a.) near the bladder, were
      investigated in unanaesthetized rats with and without bladder outlet obstruction.
      2. In normal rats, RP 67,580, given i.t. in doses of 2 and 20 nmol per rat,
      decreased micturition pressure, but did not change other cystometric parameters.
      After 20 nmol of RP 67,580, dribbling incontinence due to retention was observed
      in 1 out of 7 animals. This effect was reversible. I.t. RP 67,580 in a dose of 2
      nmol, had no effect on hyperactivity induced by intravesically instilled
      capsaicin. 3. In animals with bladder hypertrophy secondary to outflow
      obstruction, RP 67,580, given i.t. in a dose of 2 nmol per rat, decreased the
      micturition pressure, but had no effect on other cystometric parameters. After 20
      nmol, dribbling incontinence due to retention was observed in 5 out of 7 animals.
      4. RP 67,580, given i.a. in a dose of 4 nmol, had little effect on the
      cystometric parameters investigated, both in normal animals and rats with bladder
      hypertrophy. 5. SR 48,968, given i.t. in doses of 2 and 20 nmol per rat, had no
      clear-cut effects on the micturition pattern in normal rats, or rats with bladder
      hypertrophy. However, the drug reduced capsaicin-induced bladder hyperactivity.
      When given i.a. in a dose of 4 nmol, SR 48,968 had no effect on cystometric
      parameters in normal rats or rats with bladder hypertrophy. 6. The effects of
      both RP 67,580 and SR 48,968 were stereoselective, their enantiomers (RP 68,651
      and SR 48,965) being inactive.7. These results thus suggest that at the spinal
      level there is a tachykinin involvement (via NK,receptors) in the micturition
      reflex induced by bladder filling, both in normal rats, and, more clearly, in
      animals with bladder hypertrophy secondary to outflow obstruction. The bladder
      response to filling was not influenced by blockade of vesical NKI and NK2
      receptors. On the other hand, the bladder hyperactivity evoked by intravesical
      capsaicin seems to involve NK2 receptors both at the bladder and spinal levels.

PMID- 7812600
TI  - Effect of in vivo desensitization to leukotriene B4 on eosinophil infiltration in
      response to C5a in guinea-pig skin.
AB  - 1. The effect of in vivo desensitization to leukotriene B4 (LTB4) on eosinophil
      infiltration in response to recombinant C5a was examined in guinea-pig skin. 2.
      LTB4 (10-300 ng) and C5a (1-10 micrograms) caused a dose-dependent increase in
      the levels of eosinophil peroxidase activity (a measure of eosinophil
      infiltration) 4 h after injection into guinea-pig skin. Leukotriene B4 and C5a
      were approximately equipotent on a molar basis. Platelet activating factor (0.01
      10 micrograms) also caused eosinophil accumulation but was much less active than
      LTB4 or C5a. 3. 20-Hydroxy-LTB4 caused a dose-dependent desensitization of
      eosinophil responses to LTB4 (ED50 = 1.6 micrograms kg-1, s.c.) and partially
      reduced responses to C5a. At a dose of 20-hydroxy-LTB4 (10 micrograms) which
      inhibited responses to LTB4 completely, responses to C5a were reduced by 56.5 +/-
      1.8% (n = 5). The structurally related metabolite of 20-hydroxy-LTB4, 20-carboxy
      LTB4, which does not cause desensitization to the effects of LTB4, did not
      inhibit eosinophil infiltration in response to C5a. 4. The LTB4 receptor
      antagonist, SC-41,930 (10 mg kg-1, p.o.), also inhibited eosinophil accumulation
      in response to C5a by 63.0 +/- 3.9% (n = 5) at a dose which inhibited responses
      to LTB4 by 86.5 +/- 1.9% (n = 5). 5. These data indicate that eosinophil
      infiltration in response to C5a may, in part, be mediated by the generation of
      secondary chemotactic factors such as LTB4.

PMID- 7812601
TI  - Hyperpolarization by opioids acting on mu-receptors of a sub-population of rat
      periaqueductal gray neurones in vitro.
AB  - 1. The actions of opioids on membrane properties of rat periaqueductal gray
      neurones were investigated using intracellular recordings from single neurones in
      brain slices. Morphological properties and anatomical location of each impaled
      neurone were characterized by use of intracellular staining with biocytin. The
      present paper primarily considers neurones which were directly hyperpolarized by
      opioids. The accompanying paper considers inhibition of synaptic transmission by
      opioids. 2. Met-enkephalin (10-30 microM) hyperpolarized 29% (38/130) of
      neurones. The hyperpolarization was fully antagonised by naloxone (1 microM, n =
      3). The response to Met-enkephalin was not affected by agents which block
      synaptic neurotransmission (1 microM tetrodotoxin, and 0.1 microM tetrodotoxin +
      4 mM Co2+, n = 3). 3. The specific mu-receptor agonist, D-ala-met-enkephalin
      glyol (3 microM, n = 17) produced hyperpolarizations of similar amplitude to
      those produced by Met-enkephalin (10-30 microM). The EC50 of D-ala-met-enkephalin
      glyol was 80 nM and the maximum response was achieved at 1-3 microM. The delta
      receptor (D-Pen-D-Pen-enkephalin, 3 microM, n = 7) and kappa-receptor (U50488H, 3
      microM, n = 5) agonists had no effect on the membrane properties of these
      neurones. 4. The opioid-induced hyperpolarization was associated with an
      increased potassium conductance. Hyperpolarizations were accompanied by a
      significant decrease in membrane resistance between -70 and -80 mV, and a
      significantly greater decrease between -110 and -140 mV (n = 16).
      Hyperpolarizations reversed polarity at -111 +/- 3 mV (n = 16), close to the
      expected equilibrium potential for potassium ions. The reversal potential of
      outward currents increased by 24 mV when the extracellular potassium
      concentration was raised from 2.5 to 6.5 mM, which is close to the value
      predicted by the Nernst equation (25 mV) for a potassium conductance.5. Resting
      inward rectification (reduced input resistance at potentials more negative than -
      100 mV in the absence of opioids) was significantly greater in neurones which
      were hyperpolarized by opioids than in those which were not hyperpolarized. The
      amplitude of action potential after hyperpolarizations was significantly smaller
      in neurones which were hyperpolarized by opioids. Other membrane properties did
      not differ significantly between opioid-sensitive and -insensitive neurones.6.
      Neurones hyperpolarized by opioids were multipolar (58%), triangular (21%) or
      fusiform (5%) in shape with a soma diameter of 22 +/- 1 microm (n = 19, longest
      axis). Dendritic spread was in a large radiating pattern, usually in all
      directions, with axons usually originating from primary dendrites. The axons were
      usually branched and projected in several directions. Morphological properties
      did not differ significantly between opioid-sensitive and -insensitive
      neurones.7. Neurones hyperpolarized by opioids were located predominantly in the
      lateral periaqueductal gray,as well as in the more dorsal areas of the
      ventrolateral periaqueductal gray, whereas neurones not hyperpolarized by opioids
      were located in the more ventral areas of the ventrolateral periaqueductal
      gray.8. These studies demonstrate that opioids acting on micro-receptors increase
      potassium conductance in a sub-population of large neurones located predominantly
      in the lateral column of the periaqueductal gray. The neurones hyperpolarized by
      opioids could be involved in the antinociceptive actions of opioids, but might
      also be involved in other functions because a large proportion lie outside of the
      main'antinociceptive zone' of the periaqueductal gray. It is also unlikely that
      these neurones are GABAergic,suggesting that they might not participate in the
      postulated antinociceptive action of opioids mediated via disinhibition of
      neurones which project to the ventral medulla.

PMID- 7812602
TI  - Effects of chronic infusions of alpha-trinositol on regional and cardiac
      haemodynamics in conscious rats.
AB  - 1. Male, Long Evans rats (350-450 g) were chronically instrumented for the
      measurement of renal, mesenteric and hindquarters haemodynamics, and were given
      three consecutive, 24 h infusions of vehicle (sterile saline at 0.3 ml h-1, n =
      8) or alpha-trinositol (D-myo-inositol-1,2,6-triphosphate) at 5, 20 and 80 mg kg
      1 h-1 (0.3 ml h-1; n = 9). During infusion of alpha-trinositol at 5 or 20 mg kg-1
      h-1, cardiovascular changes were little different from those seen during saline
      infusion. However, during infusion of alpha-trinositol at 80 mg kg-1 h-1 there
      were increases in hindquarters vascular conductance, renal flow and vascular
      conductance, that were all significantly different from the changes seen in the
      saline group. Infusion of alpha-trinositol at the high dose in naive rats (n = 8)
      had even more marked vasodilator effects. 2. Two groups of rats (n = 8 in each),
      chronically instrumented for the measurement of cardiac haemodynamics, were given
      48 h infusions of saline (0.3 ml h-1) or alpha-trinositol (2 mg kg-1 bolus, 80 mg
      kg-1 h-1 infusion at 0.3 ml h-1). During the infusion of saline, there were
      slight reductions in heart rate, cardiac index, peak aortic flow, dF/dtmax and
      central venous pressure. In the animals receiving alpha-trinositol, with the
      exception of central venous pressure, all the above variables, together with
      total peripheral conductance, increased. 3. These results, collectively, indicate
      that incremental infusions of alpha-trinositol do not reveal its full vasodilator
      potential, possibly due to concurrent activation of counter-regulatory
      vasoconstrictor mechanisms. However, infusion of alpha-trinositol at a high dose
      causes substantial increases in renal,mesenteric and hindquarters flows and
      vascular conductances, supported by significant increases in indices of cardiac
      inotropism. Such effects, in the absence of significant hypotension, tachycardia
      or signs of desensitization, give alpha-trinositol a unique cardiovascular
      profile.

PMID- 7812603
TI  - The 5-HT1-like receptor mediating the increase in canine external carotid blood
      flow: close resemblance to the 5-HT1D subtype.
AB  - 1. It has recently been shown that the increase in external carotid blood flow
      induced by 5-hydroxy-tryptamine (5-HT) in the anaesthetized dog, being mimicked
      by 5-carboxamidotryptamine (5-CT), inhibited by methiothepin, vagosympathectomy
      and sympatho-inhibitory drugs, and resistant to blockade by ritanserin and MDL
      72222, is mediated by stimulation of prejunctional 5-HT1-like receptors leading
      to an inhibitory action on carotid sympathetic nerves; these 5-HT1-like receptors
      are unrelated to either the 5-HT1A, 5-HT1B or 5-HT1C (now 5-HT2C) receptor
      subtypes. Inasmuch as 5-CT, 5-methoxytryptamine, sumatriptan and metergoline
      display high affinity, amongst other 5-HT binding sites, for the 5-HT1D subtype,
      in the present study we have used these drugs in an attempt to determine whether
      the above inhibitory prejunctional 5-HT1-like receptors correlate with the 5-HT1D
      subtype. 2. One-minute intracarotid (i.c.) infusions of 5-HT (0.3, 1, 3 and 10
      micrograms), 5-CT (0.01, 0.03, 0.1 and 0.3 micrograms), 5-methoxytryptamine (1,
      3, 10 and 30 micrograms) and sumatriptan (1, 3, 10, 30 and 100 micrograms)
      resulted in dose-dependent increases in external carotid blood flow (without
      changes in mean arterial blood pressure or heart rate) with the following rank
      order of agonist potency: 5-CT >> 5-HT > 5-methoxytryptamine > or = sumatriptan.
      Interestingly, sumatriptan-induced vasodilatation was followed by a more
      pronounced vasoconstriction. 3. The external carotid vasodilator effects of 5-HT,
      5-CT, 5-methoxytryptamine and sumatriptan were dose-dependently and specifically
      antagonized by metergoline (10, 30 and/or 100 micrograms kg-1, i.v.). In
      addition, 5-methoxytryptamine- and sumatriptan-induced vasodilator effects were,
      respectively, markedly inhibited or abolished after vagosympathectomy, as
      previously shown for 5-CT and 5-HT.4. Sumatriptan showed tachyphylaxis in its
      vasodilator component and antagonized 5-HT-induced external carotid
      vasodilatation in a specific manner, suggesting that a common site of action may
      be involved.5. Taken together, the above results support our contention that 5
      HT, 5-CT, 5-methoxytryptamine and sumatriptan produce external carotid
      vasodilatation in the dog by an action that might primarily involve a
      prejunctional inhibition on carotid sympathetic nerves; a secondary component of
      this vasodilator response may be postsynaptic (endothelium-dependent and/or even
      directly on the vasculature).Based on the rank order of agonist potency,
      inhibition by vagosympathectomy and blockade by metergoline, we suggest that the
      inhibitory prejunctional 5-HT1-like receptors mediating external carotid
      vasodilatation in the dog closely resemble the 5-HTID receptor subtype. The
      pharmacological profile of these receptors is similar (sympathetic nerves of the
      rat kidney and human saphenous vein, as well as porcine coronary endothelium) to
      other putative 5-HTID receptors mediating vascular responses.

PMID- 7812604
TI  - Characterization of the 5-hydroxytryptamine receptor type involved in inhibition
      of spontaneous activity of human isolated colonic circular muscle.
AB  - 1. Experiments were carried out to characterize pharmacologically the 5
      hydroxytryptamine (5-HT) receptor types which mediate inhibition of spontaneous
      contractions of the intertaenial circular muscle in human isolated colon. 2. 5-HT
      caused a reproducible concentration-dependent inhibition of spontaneous
      contractions of the circular muscle of human colon in vitro with a mean EC50
      value of 0.2 microM and 95% confidence limits of 0.1-0.5 microM. No evidence for
      a contractile action of 5-HT was found. Tetrodotoxin (TTX, 1.5 microM) caused a
      rightward shift of the concentration-response curve of 5-HT with a concentration
      ratio of 2.9. 3. The inhibitory response to 5-HT was mimicked by several indoles
      with the rank order of potency 5-HT > 5-methoxytryptamine = alpha-methyl-5-HT > 5
      carboxamidotryptamine >> 2-methyl-5-HT. 5-Hydroxyindalpine was inactive. 4. The
      substituted benzamides were agonists with the following rank order of potency, 5
      HT > renzapride > zacopride > metoclopramide > cisapride. 5. The inhibitory
      responses to 5-HT were not inhibited by methysergide (10 microM) or methiothepin
      (1 microM), which are antagonists selective for 5-HT1-like and 5-HT2 receptors,
      nor by ondansetron (10 microM) which is an antagonist at 5-HT3 receptors. 6. The
      inhibitory responses induced by 5-HT and 5-methoxytryptamine were competitively
      antagonized by a weak 5-HT4 receptor antagonist, tropisetron, with pKB values of
      approximately 6. Tropisetron had no significant effect on the inhibitory response
      curve produced by isoprenaline (0.01-100 microM). 7. The pharmacological profile
      of the 5-HT-evoked relaxations of human colon circular muscle are consistent with
      activation of a 5-HT4-like receptor.

PMID- 7812605
TI  - Infection by HIV-1 blocked by binding of dextrin 2-sulphate to the cell surface
      of activated human peripheral blood mononuclear cells and cultured T-cells.
AB  - 1. Structural analogues of a sulphated polysaccharide, dextrin sulphate, were
      synthesized and tested for their ability to block infection by HIV-1. Using the T
      cell lines, C8166 and HPB-ALL, and the laboratory adapted strains of HIV-1.MN,
      HIV-1.IIIb and HIV-1.RF, dextrin 2-sulphate (D2S) combined the best combination
      of high anti-HIV-1 activity (95% inhibitory concentration (IC95) = 230 nM) and
      low anticoagulant activity. It also blocked infection of activated peripheral
      blood mononuclear (PBMN) cells by five primary viral isolates at an IC95 of 230
      3700 nM depending upon the primary viral isolate tested. 2. In saturation binding
      studies, [3H]-D2S bound to a cell surface protein on HPB-ALL cells in a specific
      and saturable manner with a Kd of 82 +/- 14 nM and a Bmax of 4.8 +/- 0.3
      pmol/10(6) cells. It bound to other human T-cell lines in a similar manner. 3.
      There was very little binding of [3H]-D2S to freshly isolated PBMN cells (Bmax
      0.18 +/- 0.03 pmol/10(6) cells) and these cells could not be infected by HIV-1.
      Culture of PBMN cells in lymphocyte growth medium (LGM) containing IL-2 did not
      significantly change the Bmax of [3H]-D2S. In contrast, PBMN cells which had been
      cultured with phytohaemagglutinin (PHA; 5 micrograms ml-1) for 72 h had a Bmax of
      [3H]-D2S binding of 7.2 +/- 0.1 pmol/10(6) cells and these cells could be
      infected by HIV-1. Removal of the PHA and further culture of the PBMN cells in
      LGM containing IL-2 resulted in a fall in the Bmax to 2.0 +/- 0.1 pmol/10(6)
      cells. The Kd of binding did not change significantly during the course of these
      experiments.4. [3H]-D2S did not bind to freshly isolated erythrocytes or to
      erythrocytes which had been cultured in PHA for 72 h.5. These results suggest
      that there is a relationship between the expression of the [3H]-D2S binding
      protein on the plasma membrane of PBMN cells and the susceptibility of these
      cells to infection by HIV- 1.

PMID- 7812606
TI  - Action of adenosine receptor antagonists on the cardiovascular response to
      defence area stimulation in the rat.
AB  - 1. The action of adenosine in the mediation of the cardiovascular changes
      associated with the defence reaction has been investigated in the rat using two
      A1 receptor antagonists. 2. Cumulative doses of 1,3 dipropyl-cyclopentylxanthine
      (DPCPX) (0.3-3 mg kg-1) and ethanol (0.03-0.25 ml) and bolus doses of DPCPX (3 mg
      kg-1) and 8-sulphophenyltheophylline (8-SPT) (20 mg kg-1) were given into alpha
      chloralose, paralysed and artificially ventilated rats. Recordings were made of
      arterial blood pressure and heart rate. 3. Ethanol, the vehicle for DPCPX, failed
      to modify the magnitude of the defence response; however, cumulative doses of
      DPCPX produced a dose-dependent decrease in the HDA (hypothalamic defence area)
      evoked increase in arterial blood pressure, accompanied by a similar fall in the
      magnitude of the evoked heart rate response. 4. The evoked rise in arterial blood
      pressure was reduced significantly by intravenous injection of DPCPX (3 mg kg-1)
      but not 8-SPT (20 mg kg-1), a purely peripherally acting adenosine antagonist. 5.
      These results suggest that adenosine acting at A1 receptors located in the
      central nervous system, is involved in the HDA-evoked pressor response. Whilst
      the site of action of the A1 receptors is not known, possible locations are
      discussed.

PMID- 7812607
TI  - A novel antagonist, phenylbenzene omega-phosphono-alpha-amino acid, for
      strychnine-sensitive glycine receptors in the rat spinal cord.
AB  - 1. 3-[2'-Phosphonomethyl[1,1'-biphenyl]-3-yl]alanine (PMBA) is a novel glycine
      antagonist at strychnine-sensitive receptors. The chemical structure of PMBA,
      possessing both a glycine moiety and a phosphono group, is quite different from
      that of strychnine. 2. In the spinal motoneurone of newborn rats, glycine (100
      microM-1 mM) induced depolarizing responses in a concentration-dependent manner.
      PMBA effectively inhibited depolarizing responses to glycine and other agonists,
      such as taurine and beta-alanine. The dose-response curves for glycine were
      shifted to the right in an almost parallel manner (pA2 value: 5.30 +/- 0.23, n =
      5) by PMBA which was about 60 times less potent than strychnine (pA2 value: 7.08
      +/- 0.21, n = 5) as a glycine antagonist. 3. PMBA (1-100 microM) did not interact
      with modulatory glycine sites on N-methyl-D-aspartate (NMDA) receptors, which
      suggests a high selectivity of PMBA for strychnine-sensitive glycine receptors.
      At considerably high concentrations (0.1 mM-1 mM), PMBA depressed responses to
      GABA (pA2 value: 3.57 +/- 0.24, n = 3). 4. PMBA inhibited the binding of [3H]
      strychnine to synaptosomes from adult rat spinal cords; the IC50 values of PMBA,
      glycine and strychnine were 8 +/- 2, 9 +/- 3 and 0.08 +/- 0.04 microM,
      respectively (n = 5) for [3H]-strychnine (4.8 nM). 5. PMBA is a central excitant
      drug with relatively high potency and selectivity and should be useful as a
      pharmacological probe for analysing the mechanisms underlying physiological
      functions of glycine receptors.

PMID- 7812608
TI  - Effects of protein kinase C activators upon the late stages of the ACTH secretory
      pathway of AtT-20 cells.
AB  - 1. The mouse AtT-20/D16-16 anterior pituitary tumour cell line was used as a
      model system for the study of phorbol 12-myristate 13-acetate (PMA)-mediated
      enhancement of calcium-evoked adrenocorticotrophin (ACTH) secretion. 2. PMA
      stimulated ACTH secretion from intact cells in a concentration-dependent manner.
      Other phorbol esters; phorbol 12,13-dibutyrate (PDBu) and phorbol 12,13
      didecanoate (PDD) and diacylglycerol analogues; 1-oleoyl-2-acetyl-sn-glycerol
      (OAG) and 1,2-dioctanoyl-sn-glycerol (DOG) also stimulated ACTH release from
      intact AtT-20 cells. This would suggest that activation of protein kinase C (PKC)
      stimulates ACTH secretion from AtT-20 cells. 3. Calcium stimulated ACTH secretion
      from electrically-permeabilized cells over the concentration-range of 10(-7) M to
      10(-5) M. PMA (10(-7) M) enhanced the amount of ACTH secreted at every
      concentration of calcium investigated. The PKC inhibitor, chelerythrine (10(-5)
      M) blocked the PMA (10(-7) M)-evoked enhancement of calcium (10(-5) M)-stimulated
      ACTH secretion but did not alter significantly the calcium (10(-5) M)-evoked
      secretion itself. This suggests that PKC modulates the secretory response to
      increases in intracellular calcium but does not mediate the effects of calcium.
      4. Guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S, 10(-5) M) stimulated ACTH
      secretion from permeabilized cells in the absence of calcium and was additive
      with calcium-evoked ACTH secretion up to a maximum value which could be achieved
      by calcium acting alone. This suggests that a GTP-binding protein mediates the
      secretory response to increases in the intracellular calcium. PMA (10-7 M)
      enhanced ACTH secretion stimulated by the combination of calcium and GTP-gamma-S
      (10-5 M).5. GTP-gamma-S stimulated ACTH secretion from permeabilized cells in a
      concentration-dependent manner with a threshold of 10-6 M. PMA (10-7 M) increased
      the amount of ACTH secretion evoked by every concentration of GTP-gamma-S
      investigated. Chelerythrine (10-s M) blocked the PMA (10-7 M)-evoked enhancement
      of GTP-gamma-S (10-4 M)-stimulated ACTH secretion but did not significantly alter
      GTP-gamma-S(10-4 M)-evoked secretion itself. This suggests that PKC modulates the
      secretory response to GTP-gamma-S but does not mediate the effects of GTP-gamma
      S.6. GTP-gamma-S (10-8-10-4-M) stimulated ACTH secretion from permeabilized cells
      either in the presence or absence of ATP (5 mM) indicating that its effects on
      secretion are ATP-independent.7. The results of the present study support the
      hypothesis that, in AtT-20 cells, PMA is acting at some site distal to calcium
      entry which modulates the ability of an increase in cytosolic calcium
      concentration to stimulate ACTH secretion. This site of action is either at the
      level of or at some stage distal to a GTP-binding protein which mediates the
      effects of calcium upon secretion.8. PMA, unlike adenosine 3':5'-cyclic
      monophosphate (cyclic AMP) (Guild, 1991), can stimulate ACTH secretion from
      permeabilized cells in the absence of added calcium and guanine nucleotides which
      suggests that PMA and cyclic AMP are acting through distinct mechanisms at this
      post calcium site of action.

PMID- 7812609
TI  - BMS-180560, an insurmountable inhibitor of angiotensin II-stimulated responses:
      comparison with losartan and EXP3174.
AB  - 1. This study compares the activity of BMS-180560 (2-butyl-1-chloro-1-[[1-[2-(2H
      tetrazol-5-yl)phenyl]-1H-indol-4- yl]methyl]-1H-imidazole-5-carboxylic acid), an
      insurmountable angiotensin II (AII) receptor antagonist, with that of losartan
      and EXP3174 in functional and biochemical models of AII-receptor activation. 2.
      BMS-180560 selectively inhibited [125I]-Sar1Ile8AII ([125I]SI-AII) binding to rat
      aortic smooth muscle (RASM) cell and rat adrenal cortical AT1 receptors (Ki = 7.6
      +/- 1.2 and 18.4 +/- 3.9 nM respectively) compared to adrenal cortical AT2
      receptors (Ki = 37.6 +/- 1.3 microM). The Ki values of BMS-180560 and EXP3174,
      but not losartan, varied as a function of the BSA concentration used in the
      assays, indicating that the diacid drugs bound to albumin. 3. BMS-180560 (3-300
      nM) increased the KD of SI-AII for RASM cell AT1 receptors. Only at high
      concentrations of BMS-180560 (300 nM) were Bmax values decreased. 4. BMS-180560
      inhibited AII-stimulated contraction of rabbit aorta with a calculated KB = 0.068
      +/- 0.048 nM and decreased maximal AII-stimulated contraction at 1 nM BMS-180560
      by 75%. In the presence of 0.1% BSA, a higher KB value (5.2 +/- 0.92 nM) was
      obtained. Losartan behaved as a competitive antagonist with a KB = 2.6 +/- 0.13
      nM. Contraction stimulated by endothelin-1, noradrenaline, KCl, or the TXA2
      receptor agonist U-46619 were unaffected by BMS-180560 (1 nM). 5. AII stimulated
      the acidification rates of RASM cells as measured by a Cytosensor
      microphysiometer with an EC50 of 18 nM. Losartan (30 nM) shifted the AII
      concentration-effect curves in a competitive manner whereas BMS-180560 (0.01 and
      0.1 nM) decreased the maximum responses by 60 and 75% respectively. Inhibition by
      losartan and BMS-180560 could be reversed following washout although recovery
      took longer for BMS-180560. 6. In [3H]-myoinositol-labelled RASM cells, losartan
      (30 and 200 nM), shifted the EC50 for AII-stimulated [3H]-inositol monophosphaste
      formation to higher values, with no change in the maximal response. By contrast,
      EXP3174 (0.1 to 1 nM) decreased the maximal response in a concentration-dependent
      manner (17-55%). BMS-180560 (3 and 10 nM) increased the EC50 for AII and
      decreased the maximum response by 30 and 80% respectively. The inhibition by
      EXP3174 and BMS-180560 could be reversed by inclusion of losartan (200 nM)
      indicating that the inhibition was not irreversible. 7. In conclusion, BMS-180560
      is a potent, specific, predominantly competitive, reversible All receptor
      antagonist, which displays insurmountable receptor antagonism. At concentrations
      of BMS-180560 which have no effect on receptor number, BMS-180560 produced
      insurmountable antagonism of AII-stimulated second messenger formation,
      extracellular acidification, and smooth muscle contraction.

PMID- 7812610
TI  - Factors underlying the increased sensitivity to field stimulation of urinary
      bladder strips from streptozotocin-induced diabetic rats.
AB  - 1. The responses of bladder strips from control, streptozotocin-diabetic, and
      sucrose-drinking rats to electrical field stimulation were investigated. Sucrose
      drinking rats were included as additional controls because they have enlarged
      bladders as a result of non-diabetic diuresis. 2. Bladder strips from diabetic
      rats developed more spontaneous activity than those from the two control groups.
      Indomethacin reduced the amplitude and frequency of spontaneous contractions
      suggesting that they resulted from endogenous prostaglandin formation.
      Tetrodotoxin (TTX) had little effect, while alpha, beta-methylene ATP caused
      increases in spontaneous activity. 3. Bladder strips from diabetic rats responded
      to field stimulation with greater contractions than controls in the absence of
      antagonists as well as in the presence of atropine and alpha, beta-methylene ATP.
      Increasing TTX concentrations caused a step-wise depression of the contractile
      response to electrical stimulation which was not affected by preincubation with
      either atropine or alpha, beta-methylene ATP. 4. Atropine and indomethacin had no
      effect on strength-duration curves constructed to measure threshold contractile
      responses to five pulses stimulation. The curves were shifted to the right by
      both TTX and alpha, beta-methylene ATP, indicating that the responses were
      neurogenic in nature and at least partially, the result of stimulation of P2
      purinoceptors. In the absence of drugs, bladder strips from diabetics responded
      at lower voltages and pulse widths than those of control and sucrose-drinking
      rats, suggesting that they were more excitable. 5. The response curve of bladder
      strips from diabetics to field stimulation at increasing voltage was shifted
      upwards and to the left compared to strips from control or sucrose-drinking rats.
      6. Bladder strips from diabetics responded to stimulation at increasing pulse
      width with greater responses than those from control or sucrose-drinking rats. At
      1.0 ms pulse width, the TTX-resistant response of strips from diabetic rats was
      still greater than that of the other groups, indicating that a myogenic component
      was also involved.7. The data suggest that bladder strips from diabetic rats are
      more excitable than those of control or sucrose-drinking rats. This may result
      from diabetes-induced decreases in bladder lipid or other membrane changes,
      and/or be a result of partial depolarization, perhaps related to diabetic
      neuropathy.

PMID- 7812611
TI  - Hydrolysis of iodine labelled urodilatin and ANP by recombinant neutral
      endopeptidase EC. 3.4.24.11.
AB  - 1. Urodilatin is a 32 amino-acid peptide of similar sequence to atrial
      natriuretic peptide (ANP), with four additional amino-acids at the N-terminus.
      Although ANP and urodilatin bind to the same receptors with similar affinities,
      urodilatin is more active than ANP as a natriuretic agent. Previous studies,
      using neutral endopeptidase EC 3.4.24.11 (NEP) derived from crude membrane
      preparations, were inconclusive, but suggested that urodilatin was more resistant
      than ANP to degradation by this enzyme. In the present study, we compared the
      degradation rates of [125I]-urodilatin and [125I]-ANP by pure recombinant NEP
      (rNEP). 2. Incubation of radioactively labelled ANP with rNEP resulted in a much
      more rapid degradation of the peptide than that for labelled urodilatin. 3. Both
      phosphoramidon and SQ-28,603, potent inhibitors of NEP, completely protected both
      peptides from metabolism by rNEP. 4. The circular dichroism spectra of the two
      peptides indicate that they are very similar and exist largely in unordered or
      flexible conformations. 5. These results support the relative resistance of
      urodilatin to NEP, and indicate that urodilatin may be of use as a therapeutic
      agent, in conditions in which ANP is ineffective.

PMID- 7812612
TI  - Antifibrillatory effects of clofilium in the rabbit isolated heart.
AB  - 1. This study was designed to determine whether clofilium exhibits
      antifibrillatory activity in a pinacidil + hypoxia-induced model of ventricular
      fibrillation (VF) in Langendorff-perfused hearts. 2. Ten minutes after exposure
      to vehicle or clofilium (0.1, 1.0 and 10.0 microM), hearts were exposed to
      pinacidil (1.25 microM), then subjected to 12 min of hypoxia and reoxygenated.
      Onset to VF was recorded. Additional groups of hearts were pretreated with UK
      68,798 (1.0, 3.0 and 10.0 microM), a delayed rectifier channel blocker, and 5
      hydroxydecanoate (10 microM), a known ATP-dependent K+ channel blocker, and
      subjected to an identical protocol. 3. Clofilium decreased the incidence of VF in
      a concentration-dependent manner; 7/9 control hearts developed VF vs 1/9 hearts
      (P = 0.007, Fisher's Exact) treated with 10.0 microM clofilium. In addition, 5
      hydroxydecanoate protected hearts from VF, while UK-68,798 pretreatment did not.
      4. In a separate group of hearts, electrically-induced VF was converted to sinus
      rhythm in 10/11 hearts after clofilium was introduced as a bolus. 5. Clofilium is
      capable of preventing VF in the rabbit isolated heart in a concentration
      dependent manner. We have data to suggest that the ability of clofilium to
      attenuate the effects of pinacidil+hypoxia in our model may include blockade of
      metabolically active K+ channels, i.e., KATP (glibenclamide-sensitive) channel.

PMID- 7812613
TI  - Loss of contractile activity of endothelin-1 induced by electrical field
      stimulation-generated free radicals.
AB  - 1. Electrical field stimulation (EFS; 10 V, 10 Hz, 2 ms) of porcine coronary
      artery strips precontracted with 10 nM endothelin-1 (ET-1) for 5 min caused a
      biphasic response, consisting of a slight contraction during EFS and a marked and
      irreversible relaxation just after EFS. This irreversible relaxation after EFS
      has never been investigated. In the present study, we have investigated the
      mechanism of the relaxation after EFS. 2. The EFS-induced response was not
      affected by the presence or absence of endothelium and was insensitive to 10
      microM tetrodotoxin (TTX). 3. In the presence of free radical scavengers (40 u ml
      1 superoxide dismutase (SOD), 1200 u ml-1 catalase or 80 mM D-mannitol), the
      relaxation after EFS was significantly inhibited. Moreover, relaxation after EFS
      was not observed in porcine coronary artery strips precontracted with 20 mM KCl.
      4. In a cascade experiment, EFS of Krebs-Ringer solution containing 10 nM ET-1
      induced marked suppression of the contractile activity of ET-1 in porcine
      coronary artery strips, which was in accord with the observed decrease in release
      of immunoreactive ET-1 (ir-ET-1). This effect of EFS was significantly inhibited
      by each of the free radical scavengers, 3 mM vitamin C, 40 u ml-1 SOD, 1200 u ml
      1 catalase and 80 mM D-mannitol. 5. The exchange of 95% O2/5% CO2 gas for 95%
      N2/5% CO2 gas significantly inhibited the EFS-induced decrease in release of ir
      ET-1. 6. Neither superoxide anions generated by xanthine (10 JM) plus xanthine
      oxidase (0.1 micro ml-1) nor hydrogen peroxide (10 microM) exogenously added to
      Krebs-Ringer solution containing 10 nM ET-1 affected the level of ir-ET-1.7.
      Generation of hydroxyl radicals was detected in the EFS-applied Krebs-Ringer
      solution. The EFS-induced generation of hydroxyl radicals was dependent on the
      period of stimulation and 02-bubbling, and significant generation of hydroxyl
      radicals was detectable with stimulation of over 5 min.Moreover, hydroxyl
      radicals generated in 50 mM NaCl solution containing 10 nM ET-1 by H202 plus Fe2
      , i.e. the Fenton reaction, significantly decreased the level of ir-ET-l.8. These
      findings suggest that oxygen-derived hydroxyl radicals generated by EFS of
      porcine coronary artery strips inactivate ET-1, probably by structural
      modification. Thus, porcine coronary artery strips precontracted with ET-1 are
      potently relaxed by EFS.

PMID- 7812615
TI  - The electrophysiological effects of antiarrhythmic potential of a secoaporphine,
      N-allylsecoboldine.
AB  - 1. A satisfactory antiarrhythmic potential of N-allylsecoboldine, a synthetic
      derivative of secoaporphine, has been documented. Its effects on the ionic
      currents of cardiac myocytes and the influence on the electrophysiological
      properties of the conduction system in Langendorff perfused hearts were
      investigated. 2. Ionic currents were studied by voltage clamp in the whole cell
      configuration. N-allylsecoboldine blocked the Na channel with a leftward-shift of
      its half voltage-dependent inactivation and a slower rate of recovery from the
      inactivation state. Similarly, calcium inward currents were inhibited but to a
      much smaller extent. 3. N-allylsecoboldine inhibited the 4-AP-sensitive transient
      outward K current. Currents through the K1 channels were also reduced. 4. As
      compared with quinidine, N-allylsecoboldine caused a comparable degree of block
      on Na and K1 currents but blocked to a lesser extent the Ca and Ito currents. 5.
      In the perfused whole-heart model, N-allylsecoboldine caused a dose-dependent
      prolongation in sinoatrial, atrioventricular and His-Purkinje system conduction
      intervals and prolonged the effective refractory periods of the atrium, AV node,
      His-Purkinje system and ventricle. However, the basic cycle length was not
      significantly affected. As compared to quinidine, N-allylsecoboldine exerted less
      pronounced effects on both the basic cycle length and the atrial and AV nodal
      refractory periods. 6. We conclude that N-allylsecoboldine predominantly blocks
      Na and K1 channels and in similar concentrations partly blocks Ca channels and
      Ito. These effects result in a modification of the electrophysiological
      properties of the conduction system which provides a satisfactory therapeutic
      potential for the treatment of cardiac arrhythmias.

PMID- 7812614
TI  - Natriuretic peptide-induced cyclic GMP accumulation in adult guinea-pig
      cerebellar slices.
AB  - 1. Second messenger responses to natriuretic peptides were studied in guinea-pig
      cerebellar slices by use of radioactive precursors. 2. The rank order of potency
      of the different natriuretic peptides in generating [3H]-guanosine 3':5'-cyclic
      monophosphate (cyclic GMP) was atrial natriuretic peptide (ANP) > brain
      natriuretic peptide (BNP) >> C-type natriuretic peptide (CNP) with EC50 values of
      19.5 +/- 8.8 nM for ANP and 169 +/- 41 nM for BNP. CNP induced [3H]-cyclic GMP
      accumulation only at concentrations greater than 1 microM. 3. An additive
      response to ANP (1 microM) was observed in the presence of the adenosine receptor
      agonist, 5'-N-ethylcarboxamidoadenosine (NECA, 10 microM) or the soluble guanylyl
      cyclase activator, sodium nitroprusside (SNP, 100 microM) for [3H]-cyclic GMP
      accumulation. 4. ANP, BNP and CNP (all at 1 microM) failed to alter significantly
      either basal-, forskolin- (10 microM), isoprenaline- (100 microM), or NECA- (10
      microM) induced [3H]-cyclic AMP generation. Natriuretic peptides also did not
      change the [3H]-cyclic AMP steady-state reached after 10 min of treatment with 10
      microM forskolin. 5. Natriuretic peptides failed to elicit significant
      accumulation of [3H]-inositol phosphates at concentrations up to 10 microM. 6.
      These data are consistent with the presence of ANPA, rather than ANPB or
      clearance receptors (C-receptors), linked to second messenger cascades in guinea
      pig cerebellar slices.

PMID- 7812617
TI  - Sensitization by dexamethasone of lymphocyte cyclic AMP formation: evidence for
      increased function of the adenylyl cyclase catalyst.
AB  - 1. Glucocorticoids and elevations of intracellular adenosine 3':5'-cyclic
      monophosphate (cyclic AMP) may affect lymphocyte activation, proliferation and
      effector functions in similar ways. Therefore, we have investigated the effects
      of the glucocorticoid, dexamethasone, on human lymphocyte cyclic AMP formation.
      2. Treatment of resting human lymphocytes with the glucocorticoid, dexamethasone,
      sensitized prostaglandin E2-stimulated cyclic AMP accumulation in a time- and
      concentration-dependent manner. 3. In membranes of lymphocytes treated for 24 h
      with 100 nM dexamethasone, maximal adenylyl cyclase activity stimulated by
      prostaglandin E2, isoprenaline, guanosine 5'-triphosphate (GTP), forskolin and
      MnCl2 was significantly enhanced; the EC50 for these agents was not significantly
      altered. 4. beta 2-Adrenoceptor density, immunodetectable alpha-subunits of the G
      proteins Gs and Gi, and pertussis toxin-substrates were not significantly altered
      by dexamethasone treatment. 5. In dexamethasone-treated lymphocytes,
      prostaglandin E2-mediated inhibition of concanavalin A-induced Ca2+ elevations
      was doubled compared to control cells. 6. Based on these data and the observation
      that enhancement of forskolin- and MnCl2-stimulated adenylyl cyclase activity
      could quantitatively account for the enhancement of prostaglandin E2-,
      isoprenaline- or GTP-stimulated adenylyl cyclase activity, we conclude that
      dexamethasone treatment sensitizes cyclic AMP formation in resting human
      lymphocytes by altering the adenylyl cyclase catalyst rather than G-proteins or
      hormone receptors. This results in an enhanced capability of cyclic AMP
      generating agonists to inhibit early steps of lymphocyte activation.

PMID- 7812616
TI  - Ca2+ release induced by myotoxin alpha, a radio-labellable probe having novel
      Ca2+ release properties in sarcoplasmic reticulum.
AB  - 1. Myotoxin alpha (MYTX), a polypeptide toxin purified from the venom of prairie
      rattlesnakes (Crotalus viridis viridis) induced Ca2+ release from the heavy
      fraction (HSR) but not the light fraction of skeletal sarcoplasmic reticulum at
      concentrations higher than 1 microM, followed by spontaneous Ca2+ reuptake by
      measuring extravesicular Ca2+ concentrations using the Ca2+ electrode. 2. The
      rate of 45Ca2+ release from HSR vesicles was markedly accelerated by MYTX in a
      concentration-dependent manner in the range of concentrations between 30 nM and
      10 microM, indicating the most potent Ca2+ releaser in HSR. 3. The Ca2+
      dependency of MYTX-induced 45Ca2+ release has a bell-shaped profile but it was
      quite different from that of caffeine, an inducer of Ca(2+)-induced Ca2+ release.
      4. 45Ca2+ release induced by MYTX was remarkable in the range of pCa between 8
      and 3, whereas that by caffeine was prominent in the range of pCa, i.e., between
      7 and 5.5. 5. MYTX-induced 45Ca2+ release consists of both early and late
      components. The early component caused by MYTX at low concentrations (30-300 nM)
      completed within 20 s, while the late component induced by it at higher
      concentrations (> 0.3 microM) was maintained for at least 1 min. 6. Both the
      components were almost completely inhibited by inhibitors of Ca2+ such as Mg2+,
      ruthenium red and spermine. 7. 45Ca2+ release induced by caffeine or beta,gamma
      methyleneadenosine 5'-triphosphate (AMP-PCP) was completely inhibited by high
      concentrations of procaine. Procaine abolished the early component but not the
      late one, suggesting that at least the early component is mediated through Ca(2+)
      induced Ca2+ release channels. 8. On the basis of these results, the character of
      Ca2+ release induced by MYTX was quite different from that caused by caffeine or
      AMP-PCP, suggesting that MYTX induces Ca2+ release having novel properties in
      HSR. MYTX is the first polypeptide Ca2+ inducer and has become a useful
      pharmacological tool for clarifying the mechanism of Ca2+ release from skeletal
      muscle SR.

PMID- 7812618
TI  - Binding and growth-inhibitory effect of heparin and oligo-heparin (2kDa) in
      Balb/c 3T3 cells: lack of effect on PDGF- or serum-induced inositol lipid
      turnover.
AB  - 1. The ability of heparins (bovine heparin sm 1026, Av. mol. wt. 36.9 kDa and
      bovine heparin EP 756, Av. mol. wt. 12.9 kDa) and heparin fractions of different
      molecular weights (low molecular weight heparin, LMW 2123/OP, Av. mol. wt. 4.5
      kDa and oligo-heparin, Av. mol. wt. 2 kDa) to inhibit the proliferation and
      signalling of Balb/c 3T3 fibroblasts was investigated. 2. Heparin and heparin
      fractions of 4.5 and 2 kDa significantly inhibited DNA synthesis as monitored by
      [2H]-thymidine incorporation. 3. 3H-labelled heparin fractions of 4.5 and 2 kDa
      were prepared by gel-chromatography fractionation on Sephadex G-75 of an 3H
      labelled commercial heparin after treatment with heparinase. 4. The binding of
      unfractionated and oligo-heparin of 2 kDa to Balb/c 3T3 fibroblasts was studied;
      we determined the specificity of heparin and oligo-heparin binding to the cells
      by means of displacement of bound 3H-labelled compound in response to increasing
      concentrations of unlabelled compounds. Scatchard analysis of binding data
      obtained using [3H]-heparin as ligand revealed the presence of a single class of
      high affinity binding sites (Kd = 28 nM) for heparin. Scatchard analysis of
      binding data obtained using [3H]-oligo-heparin as ligand revealed the presence of
      a single class of low affinity binding sites (Kd = 3.2 microM) for oligo-heparin.
      5. In addition heparin displaced [3H]-oligo-heparin at a concentration of
      approximately 100 fold of the Kd determined in displacement studies. Furthermore,
      oligo-heparin significantly displaced [3H]-heparin at a concentration of
      approximately 10 fold of the Kd determined by displacement studies. 6. Both
      heparin and oligo-heparin exert their inhibitory effects on Balb/c 3T3 DNA
      synthesis stimulated by PDGF or serum. However these molecules did not affect the
      inositol lipid turnover triggered by PDGF at a concentration which did not
      produce maximal response. The increase of inositol phosphate metabolism produced
      by 20% serum was also unaffected by heparin. This concentration of serum elicited
      a response comparable to that induced by a submaximal concentration of PDGF.

PMID- 7812619
TI  - Antagonism by riluzole of entry of calcium evoked by NMDA and veratridine in rat
      cultured granule cells: evidence for a dual mechanism of action.
AB  - 1. Intracellular calcium levels were measured in cultured cerebellar granule
      cells of the rat by use of the fluorescent dye, indo-1/AM. 2. Intracellular
      calcium levels were increased by depolarizing stimuli such as N-methyl-D
      aspartate (NMDA) (100 microM), glutamic acid (20 microM), and veratridine (10
      microM). This increase was essentially due to entry of external calcium. 3.
      Riluzole (10 microM) blocked responses to all the depolarizing agents. 4.
      Riluzole could still block the increase in intracellular calcium evoked by NMDA
      or glutamic acid when sodium channels were blocked by tetrodotoxin, suggesting
      that this effect is not mediated by a direct action of riluzole on the voltage
      dependent sodium channel. 5. Pretreatment of the cells with pertussis toxin (0.1
      micrograms ml-1) did not modify the increases in intracellular calcium evoked by
      NMDA, glutamic acid or veratridine. 6. In pertussis toxin-treated cells, riluzole
      could no longer block responses to excitatory amino acids, but still blocked
      responses to veratridine. 7. It is concluded that riluzole has a dual action on
      cerebellar granule cells, both blocking voltage-dependent sodium channels and
      interfering with NMDA receptor-mediated responses via a pertussis toxin-sensitive
      mechanism. Furthermore, these two processes have been shown to be independent.

PMID- 7812620
TI  - Benzodiazepine-induced intestinal motor disturbances in rats: mediation by omega
      2 (BZ2) sites on capsaicin-sensitive afferent neurones.
AB  - 1. The central and peripheral effects of the omega (benzodiazepine) site ligands,
      clonazepam, alpidem, zolpidem, triazolam, flumazenil, ethyl beta carboline-3
      carboxylate (beta-CCE) and N-methyl beta carboline-3-carboxylate (beta-CCM) on
      intestinal myoelectrical activity were evaluated in conscious rats, chronically
      fitted with Nichrome electrodes implanted on the duodenum and jejunum. The
      localization of the omega (benzodiazepine) receptors involved in these effects
      was evaluated by use of systemic and perivagal capsaicin treatments. 2. When
      administered intraperitoneally (i.p.) the omega site inverse agonists beta-CCE
      and beta-CCM, and the omega site antagonist flumazenil, did not affect the
      duodeno-jejunal motility. Alpidem and zolpidem, two selective omega 1 site
      agonists induced an inhibition of migrating myoelectric complexes (MMCs) only at
      a high dose (5 mg kg-1). In contrast, clonazepam (a mixed omega 1/omega 2
      agonist) and triazolam (a preferential omega 2 site agonist) disrupted the MMC
      pattern at doses as low as 0.05 mg kg-1, the effect of trizolam being of much
      longer duration than that of clonazepam. None of these drugs altered MMC-pattern
      when administered centrally (i.c.v.). 3. Administered i.p. or i.c.v. prior to
      triazolam, alpidem blocked the effect of triazolam on duodenojejunal spike
      activity. Administered i.p. prior to triazolam, flumazenil suppressed the
      triazolam-induced MMC-disruption. Previous systemic but not perivagal capsaicin
      treatment suppressed the effects of clonazepam on MMCs. 4. It is concluded that
      omega-site agonists but not, antagonist or inverse agonists, administered
      systemically induced intestinal motor disturbances which may be linked to
      activation of omega 2 (BZ2) sites located on nonvagal capsaicin-sensitive
      afferent neurones.

PMID- 7812621
TI  - Pharmacological characteristics of liriodenine, isolated from Fissistigma
      glaucescens, a novel muscarinic receptor antagonist in guinea-pigs.
AB  - 1. The pharmacological activities of liriodenine, isolated from Fissistigma
      glaucescens, were determined in isolated trachea, ileum and cardiac tissues of
      guinea-pigs. 2. Liriodenine was found to be a muscarinic receptor antagonist in
      guinea-pig trachea as revealed by its competitive antagonism of carbachol (pA2 =
      6.22 +/- 0.08)-induced smooth muscle contraction. It was slightly more potent
      than methoctramine (pA2 = 5.92 +/- 0.05), but was less potent than atropine (pA2
      = 8.93 +/- 0.07), pirenzepine (pA2 = 7.02 +/- 0.09) and 4-diphenylacetoxy-N
      methylpiperidine (4-DAMP, pA2 = 8.72 +/- 0.07). 3. Liriodenine was also a
      muscarinic antagonist in guinea-pig ileum (pA2 = 6.36 +/- 0.10) with a pA2 value
      that closely resembled that obtained in the trachea. 4. Liriodenine was 10 fold
      less potent in atrial preparations (left atria, pA2 = 5.24 +/- 0.04; right atria,
      pA2 = 5.35 +/- 0.09 and 5.28 +/- 0.07 for inotropic and chronotropic effects,
      respectively) than in smooth muscle preparations. 5. High concentration of
      liriodenine (300 microM) partially depressed the contractions induced by U-46619,
      histamine, prostaglandin F2 alpha, neurokinin A, leukotriene C4 and high K+ in
      the guinea-pig trachea. The inhibitions were characterized by a rightward shift
      in the concentration-response curves with suppression of their maximal
      contraction. 6. High concentration of liriodenine (300 microM) did not affect U
      46619- or neurokinin A-induced tracheal contraction in the presence of nifedipine
      (1 microM) or in Ca(2+)-free (containing 0.2 mM EGTA) medium. 7. Neither cyclic
      AMP nor cyclic GMP content of guinea-pig trachealis was changed by liriodenine
      (30-300 microM). 8. It is concluded that liriodenine is a selective muscarinic
      receptor antagonist in isolated trachea, ileum and cardiac tissues of guinea
      pigs. It is more potent in smooth muscle than in cardiac preparations. It also
      acts as a blocker of voltage-dependent Ca2+ channels at a high concentration (300
      microM).

PMID- 7812622
TI  - Effects of caffeine on intracellular sodium activity in cardiac Purkinje fibres:
      relation to force.
AB  - 1. An increase in cytoplasmic calcium by caffeine would lead to Ca extrusion via
      the Na/Ca exchange. The hypotheses were investigated that, as a consequence,
      caffeine might increase intracellular sodium activity (aiNa) and that the
      relation between aiNa and force might be conditioned by the Ca load. 2. Action
      potential, aiNa and contractile force were recorded in sheep Purkinje fibres
      during exposure to caffeine under conditions that decrease or increase the Ca
      load by different mechanisms. 3. In Tyrode solution, caffeine (8 mM) increased
      aiNa from 8.05 +/- 0.20 to 10.52 +/- 0.40 mM (+30.5%) and had a triphasic effect
      on force: an initial transient increase (+93.6%), a subsequent decrease (-37.1%)
      (negative inotropy) and slow partial recovery (+8.9%). 4. Decreasing the Ca load
      by means of manganese (1 mM) decreased aiNa and force. Adding caffeine re
      increased aiNa and no longer caused a negative inotropic action. Cadmium (0.2 mM)
      also decreased aiNa, and caffeine reincreased it although far less than in Tyrode
      solution. 5. High [K]o (10 mM) and tetrodotoxin (5 microM) decreased aiNa as well
      as force. In their presence, caffeine re-increased aiNa and no longer had a
      negative inotropic action. 6. Increasing the Ca load by means of high [Ca]o (8.1
      mM) increased force (+195%) and decreased aiNa, (-20.3%). Adding caffeine re
      increased aiNa (+28.1%), but immediately decreased force (-32.3%). 7. Addition of
      pyruvate (10 mM) to caffeine increased force, as it does in the presence of Ca
      overload. 8. Noradrenaline (0.1-1 microM) decreased aiNa and increased
      contractile force. In its presence, caffeine decreased aiNa further and increased
      force. 9. It is concluded that caffeine increases aiNa, even during the negative
      inotropic effect. The decrease in force appears to depend on Ca load. Thus,
      caffeine no longer decreases force under conditions that decrease Ca load (Mn,
      high [K]0, TTX) and immediately decreases force when the Ca load is
      increased(high [Ca]0). However, in the presence of noradrenaline, caffeine
      decreases aiNa and markedly increases force, as the Ca load is increased, but Ca
      can be removed from the cytoplasm into the SR.

PMID- 7812623
TI  - Characterization and transduction mechanisms of purinoceptors in activated rat
      microglia.
AB  - 1. Purinoceptor agonist-induced currents in untreated (proliferating) and
      lipopolysaccharide- (LPS; 100 ng ml-1) treated (non-proliferating) rat microglial
      cells were recorded by the whole-cell patch-clamp technique. 2. In non
      proliferating microglia, adenosine (0.01-100 microM), 2-methylthio ATP (3-3000
      nM), ATP (0.1-1000 microM), and ATP-gamma-S (1-10 microM), but not alpha,beta
      methylene ATP (alpha,beta-MeATP; 100 microM) produced a slow outward current at a
      holding potential of 0 mV. When K+ was replaced in the pipette solution by an
      equimolar concentration of Cs+ (150 mM), the 2-methylthio ATP- (300 nM) induced
      outward current disappeared. The effect of 2-methylthio ATP (300 nM) did not
      depend on the presence of extracellular Mg2+ (1 mM). The outward current response
      to 2-methylthio ATP (300 nM) was larger in proliferating than in non
      proliferating microglia. 3. ATP (1-1000 microM) evoked a fast inward current at a
      holding potential of -70 mV in nonproliferating microglia, while adenosine (100
      1000 microM) was inactive. When the effects of ATP were compared at 0 and -70 mV,
      it became evident that ATP is much more potent in evoking the outward current. 4.
      The 2-methylthio ATP- (300 nM) induced outward current was blocked by suramin
      (300 microM), but not by 8-(p-sulphophenyl)-theophylline (100 microM), while the
      adenosine- (1 microM) induced outward current had the reverse sensitivity to
      these antagonists. 5. The 2-methylthio ATP- (300 nM) induced outward current was
      inhibited by inclusion of GDP-beta-S(200 microM) into the pipette solution or by
      preincubation of microglial cells with pertussis toxin(50 ng ml-1) for 12 h. The
      2-methylthio ATP- (300 microM) induced inward current was not changed by
      intracellular GDP-beta-S (200 microM). The outward current response to adenosine
      (1 microM) was also abolished after pretreatment with pertussis toxin (50 ng ml
      1).6. Rat microglia possess both ATP-sensitive P2y- and adenosine-sensitive P1
      purinoceptors. The ATP evoked inward current is mediated by P2y-purinoceptors,
      while the ATP- and adenosine-evoked outward currents are mediated by P2y- and P1
      purinoceptors, respectively. The transduction mechanisms of the outward, but not
      the inward current activation involve a pertussis toxin-sensitive G protein.

PMID- 7812624
TI  - Inhibitory effects of capsaicin on acetylcholine-evoked responses in rat
      phaeochromocytoma cells.
AB  - 1. The effects of capsaicin on cellular responses evoked by acetylcholine (ACh)
      and those by adenosine 5'-triphosphate (ATP) were investigated in rat
      phaeochromocytoma PC12 cells. 2. Capsaicin (1 to 30 microM) suppressed dopamine
      release and the intracellular Ca2+ increase evoked by 100 microM ACh. The
      concentration-dependence of the ACh-evoked release of dopamine was not shifted
      but the maximal response was reduced by capsaicin. Dopamine release evoked by 80
      mM KCl was also suppressed by capsaicin (3 and 30 microM), but the extent of
      suppression was smaller than that of the ACh-evoked release. 3. Under whole-cell
      voltage-clamp, capsaicin (1 to 30 microM) reversibly inhibited the inward current
      activated by ACh (30 to 300 microM). The inhibition exhibited dependence on the
      concentration of ACh, and the current activated by a higher concentration of ACh
      was less inhibited. Voltage-dependence of block by capsaicin was not observed
      when it was tested either by applying a ramp pulse during the current activation
      by ACh or by eliciting the current in cells held at various potentials. 4. High
      concentrations of capsaicin (30 to 100 microM) enhanced the inward current as
      well as dopamine release evoked by 30 microM ATP. 5. The results suggest that low
      concentrations of capsaicin selectively antagonize responses mediated by
      nicotinic receptor-channels without affecting those mediated by purinoceptor
      coupled channels. As the antagonism by capsaicin of the ACh-evoked responses was
      observed at concentrations as low as 1 microM, the influence on nicotinic
      receptors should be taken into account when this compound is used as a
      pharmacological tool to deplete neuropeptides.

PMID- 7812625
TI  - The identification of apparently novel cyclic AMP and cyclic GMP
      phosphodiesterase activities in guinea-pig tracheal smooth muscle.
AB  - Phosphodiesterase (PDE) activities that were capable of hydrolysing cyclic AMP
      (Km = 6.8 +/- 2 microM) and cyclic GMP (Km = 6.7 +/- 1.6 microM) were isolated
      from tracheal smooth muscle. These enzyme(s) activities were insensitive to
      stimulation by calcium/calmodulin and to inhibition by cyclic GMP, rolipram (type
      IV inhibitor) and siguazodan (type III inhibitor). Zaprinast was a relatively
      poor inhibitor of both cyclic AMP and cyclic GMP hydrolysis (IC50 = 46 +/- 9
      microM and 45 +/- 14 microM respectively). These results suggest that tracheal
      smooth muscle may contain an apparently novel PDE. However, KCl (30 mM) which
      facilitates calcium entry in cells, depressed bradykinin-stimulated intracellular
      cyclic AMP formation, suggesting that the type I PDE may be functionally present.
      We suggest that considerable caution be exercised in identifying apparently novel
      PDE isoforms.

PMID- 7812626
TI  - Inhibition by opioids acting on mu-receptors of GABAergic and glutamatergic
      postsynaptic potentials in single rat periaqueductal gray neurones in vitro.
AB  - 1. Membrane properties of rat periaqueductal gray neurones were investigated by
      use of intracellular recordings from single neurones in brain slices.
      Morphological properties and anatomical location of each impaled neurone were
      characterized by intracellular staining with biocytin. The present paper
      considers the properties of electrically-evoked and spontaneous postsynaptic
      potentials impinging on periaqueductal gray neurones, and the actions of opioids
      on postsynaptic potentials in neurones which were not directly hyperpolarized by
      opioids. The preceding paper considers neurones which were hyperpolarized by
      opioids. 2. Electrical stimulation in the vicinity of impaled neurones evoked
      postsynaptic potentials having fast (duration at half-maximal amplitude 37 +/- 2
      ms, n = 65) and in some cases slow (duration at half-maximal amplitude 817 +/-
      187 ms, n = 3) components. Amplitudes of evoked potentials were dependent on
      stimulus voltage, membrane potential, and were abolished during superfusion with
      solutions containing tetrodoxotoxin (100 nM to 1 microM, n = 5) or Co2+ (4 mM, n
      = 2). 3. Fast postsynaptic potentials were mediated predominantly by activation
      of glutamate and GABAA receptors. The GABAA-receptor antagonist, bicucuilline (30
      microM), inhibited postsynaptic potentials by 44 +/- 8% (n = 14). The non-NMDA
      receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (10 microM), inhibited
      postsynaptic potentials by 48 +/- 6% (n = 16). Combined superfusion of
      bicuculline (30 microM) and 6-cyano-7-nitroquinoxaline-2,3-dione (10 microM)
      inhibited postsynaptic potentials by 93 +/- 1% (n = 8). Additional superfusion of
      the NMDA-receptor antagonist, (+/-)-2-amino-5- phosphonovaleric acid (50 microM)
      inhibited synaptic potentials by 94 +/- 1% (n = 3). 5. Selective micro-receptor
      agonists inhibited fast postsynaptic potentials in all neurones tested which were
      not directly hyperpolarized by opioids. Met-enkephalin (30 micro M) and Tyr-D-Ala
      Gly-MePhe-Glyol (3 microM)inhibited postsynaptic potentials by 53 +/- 3% and 49
      +/- 3%, respectively. This effect was completely antagonised by naloxone (1 micro
      M, n = 3). A small inhibition produced by the selective delta-receptor
      agonist,Tyr-D-Pen-Gly-Phe-D-Pen-enkephalin (3 micro M, 26 +/- 4%, n = 14), was
      antagonized by naloxone (1 micro M), but not by the selective delta-receptor
      antagonist, naltrindole (10 nM), suggesting non-specific micro-receptor
      activation by this agonist. The selective K-receptor agonist, U50488H (3 micro
      M), also consistently inhibited postsynaptic potentials by 45 +/- 15% (n = 4).
      However, this effect was not fully reversed by naloxone(1 micro M) suggesting a
      non-specific action.6. Both glutamatergic and GABAergic components of fast
      postsynaptic potentials were inhibited by Met-enkephalin (10 or 30 micro M). Met
      enkephalin inhibited postsynaptic potentials by 55 +/- 5% (n = 12) in the
      presence of 6-cyano-7-nitroquinoxaline-2,3-dione (10 microM, predominantly
      GABAergic component).Met-enkephalin did not affect the response to GABA applied
      directly by pressure ejection, indicating that opioids exclusively inhibited
      presynaptic release of GABA. Met-enkephalin (10-30 micro M) inhibited
      postsynaptic potentials by 48 +/- 6% (n = 11) in the presence of bicuculline (30
      micro M, predominantly glutamatergic component). In the presence of both
      bicuculline and 6-cyano-7-nitroquinoxaline-2,3-dione,Met-enkephalin inhibited the
      small residual component of the synaptic potential by 42 +/- 15% (n = 2).7.
      Frequent spontaneous synaptic potentials were also observed in 11% (10/94) of the
      neurones which were not directly hyperpolarized by opioids. These were reversibly
      abolished by bicuculline (30 micro M,n = 5) and substantially inhibited by Met
      enkephalin (30 micro M, n = 6), but were unaffected by 6-cyano-7-nitroquinoxaline
      2,3-dione (10 microM, n = 2).8. In conclusion, fast glutamatergic and GABAergic
      synaptic potentials were evoked by electrical stimulation throughout the lateral
      and ventrolateral periaqueductal gray. Slow inhibitory synaptic potentials were
      also evoked in some neurones. Opioids acting on micro-receptors inhibited both
      GABAergic and glutamatergic components of synaptic potentials throughout this
      brain region.

PMID- 7812627
TI  - Effect of dehydration and hyperosmolal hydration on lignocaine and metabolites
      disposition in conscious rabbits.
AB  - 1. The present study aimed to investigate the effect of dehydration and
      hyperosmolal hydration on the disposition of lignocaine and two of its
      metabolites, monoethylglycinexylidide (MEGX) and glycinexylidide (GX). 2.
      Lignocaine was infused to three groups of conscious rabbits: controls, rabbits
      previously deprived of water for 48 h and rabbits receiving an infusion of 2.5%
      NaCl. 3. In dehydrated and hyperosmolal-hydrated rabbits, plasma osmolality was
      321 +/- 1 and 313 +/- 1 mOsm kg-1, respectively (P < 0.01 compared to controls,
      285 +/- 1 mOsm kg-1). In dehydrated animals, baseline values of plasma arginine
      vasopressin (AVP) concentrations and plasma renin activity (PRA) were higher than
      in controls, i.e. 12.4 +/- 1.4 pg ml-1 and 15.4 +/- 1.7 ng AI ml-1 h-1 vs. 3.4 +/
      0.2 pg ml-1 (P < 0.01), and 5.1 +/- 0.6 ng AI ml-1 h-1 (P < 0.01), respectively;
      atrial natriuretic peptide (ANP) decreased from 55 +/- 11 to 32 +/- 4 pg ml-1 (P
      < 0.05). Compared to controls, hyperosmolal hydration only increased AVP to 15.5
      +/- 0.7 pg ml-1 (P < 0.01). 4. Under both experimental conditions, lignocaine
      plasma concentrations were almost double (P < 0.01) those in controls, due to a
      lower systemic clearance, e.g. 54 +/- 3 and 59 +/- 1 vs. 96 +/- 5 ml min-1 kg-1,
      respectively. Plasma levels of MEGX increased (P < 0.01) only in dehydrated
      animals, although GX plasma concentrations were augmented (P < 0.01) about three
      fold in both groups of animals. The changes in lignocaine plasma concentrations
      were correlated with AVP levels (R2 = 0.5168, P<0.001).5. To document the effect
      of AVP on hepatic plasma flow, another group of rabbits received on separate
      occasions two doses of AVP (17 and 84 ng kg-1) while receiving an infusion of in
      docyanine green. AVP reduced hepatic plasma flow from 38.9 +/-2.7 ml min-1 to
      19.6 +/-2.5 ml min-1 (P<0.01).The predicted maximal AVP-induced decrease in
      hepatic plasma flow was 19.6 ml min-1 kg- 1(Emax), and AVP concentration
      eliciting 50% of Em.. (ED50) was 28.7 pg ml-1.6 It is concluded that both
      dehydration and hyperosmolal hydration alter the disposition of lignocaine and
      two of its metabolites.

PMID- 7812628
TI  - Endothelium-derived relaxing factor released by 5-HT: distinct from nitric oxide
      in basilar arteries of normotensive and hypertensive rats.
AB  - 1. The role of the endothelium in cerebrovascular responses to 5
      hydroxytryptamine (5-HT) was investigated in spontaneously hypertensive rats
      (SHR) and normotensive Wistar-Kyoto rats (WKY) in vitro. 2. Cumulative addition
      of 5-HT caused concentration-dependent contractions in ring preparations of SHR
      basilar arteries; the contractile response was smaller in WKY basilar arteries.
      3. Removal of the endothelium enhanced markedly the contractile responses to 5-HT
      in WKY arteries but had only a slight effect in SHR arteries. The responsiveness
      to 5-HT in WKY arteries after removal of endothelium was comparable to that in
      SHR arteries. 4. The endothelium-dependent relaxation induced by acetylcholine in
      WKY basilar arteries was almost abolished by treatment with 10 microM methylene
      blue or 10 microM NG-nitro-L-arginine (L-NOARG). However, the response to 5-HT
      was not affected by treatment with methylene blue, L-NOARG or indomethacin. 5.
      Application of 10-20 mM K+ or 3.2 mM tetraethylammonium (TEA) did not change
      significantly, or only increased slightly, the resting tension, but markedly
      enhanced the contractile response to 5-HT in WKY arteries with endothelium. In
      contrast, the submaximal response to 5-HT in SHR arteries with endothelium was
      significantly enhanced by 0.3 mM TEA. 6. In the presence of 1 mM TEA, the
      application of 10 microM L-NOARG further enhanced the responses of 5-HT in WKY
      arteries with endothelium. In SHR arteries with endothelium, 10 microM L-NOARG
      per se enhanced slightly but significantly the responses to 5-HT. 7. These
      results indicate that 5-HT-induced contraction in basilar arteries is
      substantially attenuated by an endothelium-dependent mechanism in WKY, but to a
      much lesser extent in SHR. The major relaxing factor released by 5-HT from
      endothelium in WKY is distinct from NO and may exert its effect by activating K+
      channels.

PMID- 7812629
TI  - Investigation of the endogenous chemoattractants involved in 111In-eosinophil
      accumulation in passive cutaneous anaphylactic reactions in the guinea-pig.
AB  - 1. Eosinophil accumulation and plasma extravasation are features of type I
      allergic responses. In an attempt to characterize the mediators of these
      responses, we have examined the local accumulation of 111In-eosinophils and
      leakage of 125I-human serum albumin (125I-HSA) during passive cutaneous
      anaphylaxis (PCA) reactions and in response to defined inflammatory mediators in
      the guinea-pig. Animals were passively sensitized by intradermal injection of
      anti-bovine gamma globulin antibody (50 microliters, 1/50 dilution). After 20-24
      h, animals were injected intravenously with 111In-eosinophils and 125I-HSA for
      the measurement of cell accumulation and plasma leakage, respectively. 2. When
      injected into sensitized sites, antigen caused a dose-related increase in the
      accumulation of 111In-eosinophils and plasma leakage in guinea-pig skin. Time
      course experiments over 24 h revealed that the maximal rate of 111In-eosinophil
      accumulation occurred over the first 90 min, with little accumulation at later
      time points. Plasma leakage was completed within the first 30 min after
      challenge. Responses to the mast cell degranulator, compound 48/80, exhibited
      very similar responses to the PCA reaction. 3. Co-injection of antigen with the
      PAF antagonist, WEB 2086 (10(-7) mol/site) or the 5-lipoxygenase inhibitor, PF
      5901 (10(-7) mol/site) did not significantly alter the accumulation of 111In
      eosinophils or plasma leakage, whereas these drug doses abolished responses to
      exogenous PAF (10(-9) mol/site) and arachidonic acid (AA, 3 x 10(-8) mol/site),
      respectively. The H1 receptor antagonist chlorpheniramine (2.5 x 10(-8) mol/site)
      did not reduce antigen-induced 111In-eosinophil accumulation. Drug combinations
      were also injected with antigen into sensitized sites, but were unable to reduce
      "'In-eosinophil accumulation.4. These results indicate that anaphylactic
      eosinophil accumulation in this model involves mediators other than histamine,
      PAF or lipoxygenase products. This is in contrast to plasma leakage in this
      reaction, which can be abolished by a combination of antagonists blocking these
      mediators.

PMID- 7812630
TI  - Inhibition by KF17837 of adenosine A2A receptor-mediated modulation of striatal
      GABA and ACh release.
AB  - 1. The effect of the A2A adenosine receptor agonist, 2-p-(2
      carboxyethyl)phenethyl-amino-5'-N-ethylcarboxamidoadenosine (CGS 21680) on the
      potassium evoked release of [3H]-gamma-aminobutyric acid ([3H]-GABA) from nerve
      terminals derived from the caudate-putamen and the globus pallidus of the rat was
      compared. In both preparations CGS 21680 (1 nM) inhibited the [3H]-GABA release
      evoked by 15 mM KCl but had no effect on that evoked by 30 mM KCl. 2. The ability
      of CGS 21680 (1 nM) to inhibit the release of [3H]-GABA from striatal nerve
      terminals was unaffected by the presence of the GABA receptor antagonists,
      bicuculline (10 microM), phaclofen (100 microM) and 2-hydroxysaclofen (100
      microM). Similarly the opioid receptor antagonist, naloxone (10 microM), the
      adenosine A1 receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 40
      nM), and the cholinoceptor antagonists, mecamylamine (10 microM) and atropine
      (100 nM) had no effect on this inhibition. 3. The ability of CGS 21680 (0.1 nM)
      to stimulate the release of [3H]-acetylcholine ([3H]-ACh) from striatal nerve
      terminals was unaffected by the presence of bicuculline (10 microM), 2
      hydroxysaclofen (100 microM), phaclofen (100 microM), naloxone (10 microM) and
      DPCPX (4 nM). 4. The novel A2A receptor antagonist, (E)-8-(3,4-dimethoxystyryl)
      1,3-dipropyl-7-methylxanthine (KF 17837), blocked the CGS 21680 (1 nM)-induced
      inhibition of [3H]-GABA efflux with an EC50 of approximately 30 nM and also
      antagonized the CGS 21680 (0.1 nM)-induced stimulation of [3H]-ACh release with
      an EC50 of approximately 0.3 nM. 5. It is concluded that the A2A adenosine
      receptor is present on both GABAergic and cholinergic nerve terminals of the rat
      striatum and that in both the caudate-putamen and the globus pallidus this
      receptor inhibits [3H]-GABA release. No evidence was seen for a difference in the
      ligand binding sites of this receptor in the two groups of nerve terminals.

PMID- 7812631
TI  - Vasoconstrictor endothelin receptors characterized in human renal artery and vein
      in vitro.
AB  - 1. We have identified the endothelin receptors present in the media of human main
      stem renal artery and vein and characterized the subtypes mediating
      vasoconstriction in these blood vessels in vitro. 2. Messenger RNA encoding both
      ETA and ETB receptors was identified in the smooth muscle layer of human renal
      artery and vein by reverse transcriptase-polymerase chain reaction assay. In
      cryostat-cut cross-sections of both vessels autoradiographical visualisation
      suggested a majority of ETA receptors. Intense binding was obtained to the non
      selective ligand [125I]-ET-1 and the ETA-selective [125I]-PD151242 but only weak
      labelling of sites by the ETB-selective [125I]-BQ3020. 3. ET-1 potently
      constricted renal artery and vein preparations with EC50 values of 4.06 nM and
      1.00 nM, respectively. Sarafotoxin 6b was approximately ten times less potent
      than ET-1 with EC50 values of 36.3 nM and 13.8 nM respectively. In the renal
      artery, ET-3 and sarafotoxin 6c showed little or no activity up to 300 nM.
      Responses to these peptides were more variable in the renal vein. Preparations
      from three individuals did not respond to ET-3 but in three further cases,
      although ET-3 was much less potent than ET-1, full dose-response curves were
      obtained. S6c elicited dose-related contractions in vein preparations from 5/6
      individuals and although more potent than ET-1, the maximum response was 30-60%
      of that obtained to ET-1. 4. ET-1-induced vasoconstriction of renal artery and
      vein was antagonized by the ETA-selective, BQ123 (3-10 microM). The dose-response
      curves to ET-1 were displaced in a parallel rightward fashion with no attenuation
      of the maximum responses. pA2 values were estimated to be 6.8 +/- 0.1 and 6.8 +/-
      0.4 for artery and vein respectively.5. These data suggest that mRNA encoding
      both ETA and ETB receptors is present in the media of human main stem renal
      artery and vein. However, autoradiographical studies indicate that the majority
      of ET receptors expressed are of the ETA subtype. The relative potencies of ET-1
      and ET-3 as vasoconstrictors of renal blood vessels in vitro is consistent with
      this being an ETA-mediated response,and therefore whilst responses to S6c
      indicate that constrictor ETB receptors may be present in renal veins from some
      individuals these are likely to be of less importance in these blood vessels.

PMID- 7812632
TI  - Close correlation of the cardioprotective effect of FK409, a spontaneous NO
      releaser, with an increase in plasma cyclic GMP level.
AB  - FK409 ((+/-)-(E)-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexeneamide) , which has
      been reported by us to be a new spontaneous nitric oxide (NO) releaser, prevented
      myocardial infarction following occlusion and reperfusion in rat coronary artery
      and increased plasma cyclic GMP level in rats, dose-dependently and significantly
      at 32 mg kg-1. Isosorbide dinitrate (ISDN), which is the most popular orally
      active NO donor used in the treatment of ischaemic cardiovascular diseases, did
      not show significant effects at 32 mg kg-1 in either experiment. Therefore, it is
      suggested that FK409 can attenuate myocardial injury during ischaemia and
      reperfusion in contrast to ISDN and a change in plasma cyclic GMP level may serve
      as an indicator of the cardioprotective effect of NO-releasing drugs.

PMID- 7812633
TI  - Phorbol ester-induced M-current suppression in bull-frog sympathetic ganglion
      cells: insensitivity to kinase inhibitors.
AB  - 1. The effects of 1-oleoyl-2-acetyl-sn-glycerol (OAG), phorbol 12-myristate 13
      acetate (PMA), 4-alpha-phorbol and muscarine on B-neurones from bull-frog
      sympathetic ganglion were studied by means of whole-cell patch-clamp recording.
      With the exception of 4-alpha-phorbol, all of these agonists reduced the steady
      state outward current recorded at -30 mV as a result of suppression of a voltage
      dependent, non-inactivating K(+)-current, the M-current, (IM). 2. Of the cells
      tested, 34% displayed bona fide responses to OAG (20 microM). The chance of
      recording a response was not decreased when the protein kinase inhibitor, 1-(5
      isoquinolinylsulphonyl)-2-methyl-piperazine (H-7; 50 or 75 microM) was included
      simultaneously in the extracellular solution and in the pipette solution. 3. The
      presence of 50 microM H-7 on both sides of the membrane or 500 nM staurosporine
      in the pipette solution did not prevent responses to brief (1-2 min) or prolonged
      (> 20 min) applications of PMA. 4. Brief (1-2 min) extracellular application of H
      7 (300 microM) suppressed IM by about 29%. 5. The most likely explanation of
      these data is that PMA and OAG modulate IM via a mechanism that is independent of
      protein kinase C (PKC). The availability of such a mechanism poses new questions
      as to the mechanism of muscarine-induced IM suppression.

PMID- 7812634
TI  - The involvement of bradykinin B1 and B2 receptor mechanisms in cytokine-induced
      mechanical hyperalgesia in the rat.
AB  - 1. Interleukin-1 beta (IL-1 beta), IL-2 and IL-8 induced a mechanical
      hyperalgesia following intra-articular (i.artic.) injection into rat knee joints,
      whereas IL-6 and tumour necrosis factor alpha (TNF-alpha) were without effect. 2.
      Co-administration of IL-1 receptor antagonist (0.1 micrograms) with IL-1 beta (1
      mu), IL-2 (10 mu) or IL-8 (0.1 mu) prevented the subsequent development of the
      hyperalgesia. 3. Co-administration of desArg9Leu8BK (0.5-5 nmol) with IL-1 beta
      (1 mu), IL-2 (10 mu) or IL-8 (0.1 mu) reduced the level of hyperalgesia at 1, 4
      and 6 h post administration, whereas Hoe 140 (5 pmol) antagonized the
      hyperalgesia only at the 1 h time point. 4. Intravenous administration of
      desArg9Leu8BK (10 nmol kg-1) or Hoe 140 (100 pmol kg-1) following IL-1 beta (1
      mu), IL-2 (10 mu), or IL-8 (0.1 mu) reversed the subsequent hyperalgesia. 5.
      Administration of desArg9BK into joints 24 h after pre-treatment with IL-1 beta
      (1 mu) produced analegsia at low doses (50 pmol) and hyperalgesia at a higher
      dose (0.5 nmol). Both these effects were blocked by desArg9Leu8BK (0.5 nmol). 6.
      Administration of desArg9BK (0.5 nmol i.artic.) to animals 24 h after pre
      treatment with IL-2 (1-100 mu) or IL-8 (0.1-10 mu) had no effect on the load
      tolerated by the treated joint. 7. Administration of indomethacin (1 mg kg-1,
      s.c.) prior to IL-1 beta (1 mu i.artic.) prevented the development of
      hyperalgesia. Administration of desArg9BK (5 pmol-0.5 nmol, i.artic.) to animals
      24 h after indomethacin and IL-1 beta pretreatment had no effect on the load
      tolerated by the treated joint. 7. Administration of indomethacin (1 mg kg-1,
      s.c.) prior to IL-1beta (1 u i.artic.) prevented the development of hyperalgesia.
      Administration of desArg9BK (5 pmol-0.5 nmol, i.artic.) to animals 24 h after
      indomethacin and IL-1 beta pretreatment had no effect on the load tolerated by
      the treated joint.8. These data suggest that both bradykinin B1 and B2 receptors
      are involved in the induction and maintenance of cytokine-induced hyperalgesia.
      They also show that the induction of B1 receptor-mediated hyperalgesia requires
      both cyclo-oxygenase products and IL-1 in vivo.

PMID- 7812635
TI  - The electrophysiological effects of dicentrine on the conduction system of rabbit
      heart.
AB  - 1. The electrophysiological effects of dicentrine, an aporphine alkaloid isolated
      from the root of Lindera megaphylla, were examined in the Langendorff perfused
      rabbit heart and rabbit isolated cardiac cells. 2. Standard electrophysiological
      characters were measured in the Langendorff perfused rabbit heart (control study)
      and after 5 min exposure to 1, 3 and 9 microM of dicentrine and during the
      subsequent recovery phase sequentially (n = 7). The same study protocols were
      performed in 0.5 to 4.5 microM quinidine (n = 7), 18 to 162 microM procainamide
      and N-acetylprocainamide (n = 7) for comparison. 3. The results showed that the
      spontaneously beating heart rate and the sinoatrial (SA) and atrioventricular
      nodal (AH) conduction time were not significantly affected by dicentrine but were
      significantly suppressed by the higher doses of quinidine (4.5 microM) and
      procainamide (162 microM). 4. The His-Purkinje conduction time was significantly
      increased by the higher dose of dicentrine, quinidine and procainamide. 5. The
      ventricular repolarization time and its effective refractory period were
      significantly increased by the higher dose of dicentrine and the other agents. 6.
      The effective refractory period of the atrium, AV node and His-Purkinje system
      were also significantly increased by dicentrine and the other agents. 7. A
      voltage clamp study revealed that the prolongation of atrial action potential
      duration by dicentrine (9 microM) was associated with a significant inhibition of
      the transient potassium outward current. As well as inhibition of the transient
      outward current, a significant inhibition of the sodium inward current by
      dicentrine was found. 8.We conclude that (1) dicentrine is potentially a useful
      antiarrhythmic agent with type Ia and type III antiarrhythmic action; (2) the
      relative potency of dicentrine on the electrophysiological function of cardiac
      tissue is 10-20 times more than that of procainamide.

PMID- 7812636
TI  - Photon pharmacology of an iron-sulphur cluster nitrosyl compound acting on smooth
      muscle.
AB  - 1. The mechanisms of action on smooth muscle of the iron-sulphur cluster nitrosyl
      compound, heptanitrosyl-tri-mu 3-thioxotetraferrate (1-), (RBS), a photosensitive
      nitric oxide donor, have been investigated in the guinea-pig taenia caeci (coli)
      in vitro. 2. After exposure to RBS (50 microM) for 30 min, and subsequent
      washout, a sustained contraction was recorded in the absence of light to either
      the agonist carbachol (50 microM) or a depolarizing concentration of KCl (23.5
      mM). Photon irradiation (> 400 nm) caused a prompt relaxation of precontracted
      RBS-treated muscle, the magnitude of which depended upon the intensity (1.1 x
      10(3) to 1.1 x 10(5) lux), duration (30 s to 20 min) and wavelength (400 to 800
      nm), of the incident illumination. 3. Repeated periods of illumination at 1.1 x
      10(4) lux produced a reversible relaxation of both carbachol and KCl-evoked tone
      in muscle pretreated with RBS (50 microM). These photorelaxations were
      reproducible at 10 min intervals for several hours with a maximal relaxation
      amounting to 80 to 90% that of the tone produced by carbachol (50 microM). 4. The
      nitric oxide synthase inhibitor, NG-nitro-L-arginine (60 microM), caused no
      inhibition of the photon-induced relaxation of RBS-treated muscle. In contrast, N
      methylhydroxylamine (2 mM), L-cysteine (10 mM), DL-dithiothreitol (2 mM),
      methylene blue (30 microM), and haemoglobin (20 microM), all reversibly but
      significantly inhibited (P < 0.001) the photorelaxation response. However,
      neither the aminothiol N-acetyl-L-cysteine (10 mM) nor the tripeptide glutathione
      (10 mM) blocked the RBS-induced photorelaxation. 5 The photolytic cleavage of RBS
      depended on the intensity and duration of illumination; it was accompanied by a
      corresponding decrease in absorbance and by the liberation of NO as measured by
      the Griess diazo reaction with sulphanilic acid. L-Cysteine (10 mM) prevented the
      decrease in absorbance and the photolytic liberation of NO.6 It is concluded that
      (i) sequestered or bound RBS, when photon-activated, liberates NO by a process
      which can be controlled by the wavelength, intensity and duration of the incident
      light, (ii) the photon-released NO rapidly relaxes the smooth muscle cells of the
      taenia coli primarily via cyclic GMP-dependent pathways which can be blocked by
      use of appropriate inhibitors, and (iii) the RBS-induced photorelaxation effect
      does not involve the activation of NO synthase. RBS is therefore a valuable
      photosensitive NO donor for establishing the functional and pharmacological
      significance of NO.

PMID- 7812638
TI  - Application of a bi-directional associative memory (BAM) network in computer
      assisted learning in chemistry.
AB  - A computer assisted learning software based on a bi-directional associative
      memory (BAM) network was developed. The software was implemented to assist
      students in associating the names of the elements in the periodic table with
      their chemical symbols. The use of the BAM facilitates the analysis and
      interpretation of students' responses. The software package can be modified
      easily as an educational tool for other disciplines.

PMID- 7812637
TI  - Neuropeptide Y in rat detrusor and its effect on nerve-mediated and acetylcholine
      evoked contractions.
AB  - 1. Immunohistochemical and isolated organ bath techniques were used to detect the
      presence of neuropeptide Y (NPY) in the rat urinary bladder and to determine its
      effect on tone, spontaneous activity and contractile responses of the detrusor
      muscle to electrical field stimulation, acetylcholine and alpha,beta-methylene
      ATP (alpha,beta-MeATP). 2. A very rich presence of NPY-immunoreactive nerve
      fibres was found mainly within the bundles of detrusor muscle cells. Chronic
      treatment with 6-hydroxydopamine did not affect the density of NPY-positive nerve
      fibres. 3. NPY (> 1 nM) enhanced the force and frequency of spontaneous
      contractions and generated a rise in the resting tone of the detrusor. These
      effects of NPY on the tone and the spontaneous activity remained unaffected by
      atropine (3 microM), indomethacin (10 microM) and aspirin (100 microM) but were
      abolished by Ca(2+)-withdrawal from the bathing medium. 4. The enhancing effects
      of NPY on the spontaneous contractions and the resting tone were not prevented by
      the induction of purinoceptor desensitization. 5. NPY (1-250 nM) potentiated
      electrical field stimulation (EFS, 1-64 Hz, 0.1 ms pulses duration, 10s train
      duration)-evoked, tetrodotoxin (0.5 microM)-sensitive contractions. The atropine
      (3 microM)-resistant component of EFS-evoked contractions was also potentiated by
      NPY. By contrast, the nifedipine (1 microM)-resistant but atropine-sensitive
      component of EFS-evoked contraction was inhibited by NPY. 6. NPY (250 nM) did not
      affect acetylcholine-evoked contractions, but potentiated alpha,beta-MeATP-evoked
      contractions. 7. It is concluded that NPY-innervation of rat urinary bladder is
      largely confined to the detrusor muscle and is abundant and mainly non
      adrenergic. It is further concluded that the enhancing effect of NPY on detrusor
      spontaneous activity and tone is caused by Ca2+ influx through nifedipine
      sensitive Ca2+ channels and is not mediated through acetylcholine or cyclo
      oxygenase-sensitive eicosanoids or ATP.8. The results are consistent with the
      hypothesis that intrinsic NPY in the rat detrusor innervation contributes to the
      motor transmission in two ways: by promoting non-cholinergic motor transmission
      and by inhibiting prejunctionally the cholinergic transmission.

PMID- 7812639
TI  - Artificial neural networks applied to classification of mutagenic activity of
      nitro-substituted polycyclic aromatic hydrocarbons.
AB  - Three-layer artificial neural networks (ANN) with back-propagation of error have
      been applied to classification of nitro-substituted polycyclic aromatic
      hydrocarbons (NPAH) based on the regularity that the structure difference of NPAH
      compounds leads to different mutagenic activity towards Salmonella typhimurium.
      The network's architecture and parameters were optimized to give maximum correct
      classification rate of 93.8% for two different classes of NPAHs: weakly active
      and strongly active ones. The results compared favourably with those obtained by
      nonlinear mapping pattern recognition method. Considering that the most important
      factor for NPAH's mutagenicity might be the electron effect of the substituted
      nitro-groups, an electrotopological state index of nitrogen atom was introduced
      additionally as one of network's inputs, and the correct classification rate was
      consequently raised to 97.5%. The network's prediction ability for untrained
      samples was also satisfactory.

PMID- 7812640
TI  - Chemical- and radiation-induced esophageal injury.
AB  - The esophageal wall can only respond to injury in a limited fashion. This article
      explores some of the protective mechanisms involved as well as current approaches
      to diagnosis and management of chemical- and radiation-induced esophageal injury.

PMID- 7812641
TI  - Severe reflux esophagitis.
AB  - Reflux esophagitis, usually the mild to moderate form, is found endoscopically in
      less than 50% of patients with classic symptoms of gastroesophageal reflux
      disease (GERD). These patients tend to have low lower esophageal sphincter
      pressures, poor esophageal clearance, and hiatal hernias. The endoscopic findings
      of distal esophageal erosions and ulcerations are a specific, but not very
      sensitive, marker of GERD. Treatment of reflux esophagitis usually requires H2
      antagonists, omeprazole, or antireflux surgery.

PMID- 7812642
TI  - Gastroesophageal reflux in pregnancy.
AB  - Gastroesophageal reflux symptoms are common in pregnancy, occurring in
      approximately 45% to 80% of gravid women. Although the symptoms associated with
      reflux in pregnancy are similar to those described in the nongravid state, some
      of the etiologies are distinct due to hormonal fluctuations and other physiologic
      changes often associated with pregnancy. Diagnostic tools and therapeutic
      regimens that might be used without hesitation in the nonpregnant patient must be
      given cautious consideration in the gravid patient due to potential fetal risks.
      This article addresses the epidemiology, pathophysiology, diagnosis, and
      treatment of gastroesophageal reflux in pregnancy.

PMID- 7812643
TI  - Infectious esophagitis.
AB  - This article presents the epidemiology, pathogenesis and pathology, clinical
      manifestations, and diagnosis and treatment of Candida, herpes simplex virus,
      cytomegalovirus, Mycobacterium tuberculosis, Aspergillus, histoplasmosis,
      blastomycosis, and HIV. Uncommon AIDS-related esophageal infections are also
      discussed.

PMID- 7812644
TI  - Chest pain of undetermined origin.
AB  - Chest pain of undetermined origin (CPUO) can be a diagnostic dilemma for both the
      primary care physician and subspecialist. This article focuses on the diagnostic
      tools used in the evaluation of CPUO, which include: prolonged ambulatory
      intraesophageal pH monitoring; esophageal manometry with provocative testing;
      ambulatory intraesophageal pressure monitoring; the role of radiology and
      endoscopy in the evaluation of chest pain; the role of psychological
      abnormalities and abnormal nociception in the pathogenesis of chest pain; and the
      clinical approach and treatment rationale for CPUO.

PMID- 7812645
TI  - Esophageal varices.
AB  - Numerous conditions lead to portal hypertension with the development of
      esophageal varices. Treatment for acute variceal hemorrhage should progress in a
      logical, stepwise fashion. Therapy after fluid resuscitation includes
      vasopressin, somatostatin, or a Sengstaken-Blakemore tube. This is followed by
      treatment with sclerotherapy, variceal ligation, or a combination of both.
      Continued bleeding is managed by more invasive measures that include radiologic
      embolization or shunting, esophageal transection, distal splenorenal shunt, or
      liver transplantation. Beta-blockade may be useful to prevent recurrent bleeding
      in compliant patients without medical conditions that would preclude use of beta
      blockade. Once control of the bleeding has been achieved, sclerotherapy or
      ligation should be used to obliterate the varices, but prophylactic use of
      sclerosant is not particularly beneficial.

PMID- 7812646
TI  - Barrett's esophagus.
AB  - Barrett's esophagus is a complication of gastroesophageal reflux disease that is
      diagnosed with increasing frequency in connection with the increased utilization
      of upper endoscopy. It remains unclear why some patients with gastroesophageal
      reflux disease develop Barrett's esophagus while others do not. The association
      of Barrett's esophagus and adenocarcinoma is well established; if not for this
      fact, Barrett's esophagus would be of little clinical importance. Endoscopic
      surveillance with a rigorous biopsy protocol for the detection of dysplasia or
      early adenocarcinoma is indicated in any patient with Barrett's esophagus who is
      a candidate for surgery. New therapeutic strategies, including profound acid
      suppression with proton pump inhibitors, laser ablation of Barrett's epithelium,
      and photodynamic therapy, are currently under evaluation for the treatment of
      Barrett's esophagus.

PMID- 7812647
TI  - Benign and malignant esophageal tumors other than squamous and adenocarcinoma.
AB  - The spectrum of esophageal tumors is diverse, although most tumors are squamous
      and adenocarcinoma. In this article the benign esophageal tumors are discussed as
      well as the uncommon malignant tumors, including the metastatic ones. Endoscopic
      pictures of most of these tumors are presented.

PMID- 7812648
TI  - Endosonography of the esophagus.
AB  - Endoscopic ultrasonography has emerged as a new method for obtaining highly
      detailed images of the esophagus. This novel imaging modality is useful in
      determining the etiology of submucosal esophageal lesions, has detected anatomic
      abnormalities in certain motility disorders, and has been used to study patients
      with portal hypertension. Endosonography should be considered the imaging method
      of choice for the pretherapeutic evaluation of patients with esophageal cancer.
      Recent data demonstrate its superior ability to determine the depth of tumor
      infiltration (T stage) and assess regional lymph adenopathy. Endoscopic
      ultrasonography provides important information that may help predict outcome in
      some patients and detect posttherapeutic recurrence in others. Certain technical
      limitations, such as patients with high-grade malignant stenosis that preclude
      complete endosonographic assessment of esophageal cancer, may be addressed in the
      future with novel, high-frequency endosonographic probes capable of traversing
      high-grade malignant stenoses.

PMID- 7812649
TI  - Regulation of TNF-mediated cell death and inflammation by human adenoviruses.
AB  - Human adenoviruses are among a growing number of human, animal, and even plant
      viruses that encode gene products that interfere with the defense mechanisms of
      the host. The host mechanisms most often affected by these viral products are the
      innate and inflammatory responses such as interferon and the proinflammatory
      cytokines interleukin-1 (IL-1) and tumor necrosis factor (TNF). This review
      discusses examples of viral anti-immune mechanisms from many different viruses
      and then focuses on the molecular interactions between adenoviruses and TNF and
      the effect of these interactions on the ensuing pathogenesis of virus infection.

PMID- 7812650
TI  - Poxviral modifiers of cytokine responses to infection.
AB  - Poxviruses include some of the most virulent of all human pathogens. In part, the
      virulence of these viruses stems from their abilities to counter host defenses
      against infection. A family of cytokine-response modifiers encoded by the
      poxviruses contribute to these countermeasures. The poxviral cytokine-response
      modifiers appear to affect cytokine responses in at least four different ways:
      (a) by inhibiting the synthesis and release of cytokines from infected cells; (b)
      by interfering with the interaction between a cytokine and its receptor; (c) by
      inhibiting cytokine signal transmission; and (d) by synthesizing virus-encoded
      cytokines that antagonize the effects of host cytokines mediating antiviral
      processes. Known poxviral, cytokine-response modifiers include CrmA, an inhibitor
      of the interleukin-1 beta converting enzyme; several secreted soluble receptors
      for tumor necrosis factor, interleukin-1, and interferon-gamma; and poxvirus
      encoded growth factors resembling epidermal growth factor. Collectively, these
      and other as yet unidentified cytokine-response modifiers contribute to the
      inhibition of a variety of nonspecific and virus-specific immune defenses against
      virus infection. Information gained on the mechanisms used by poxviruses to
      modify cytokine-mediated processes should assist the development of novel
      therapies for a variety of diseases.

PMID- 7812651
TI  - Epstein-Barr virus protein LMP2A regulates reactivation from latency by
      negatively regulating tyrosine kinases involved in sIg-mediated signal
      transduction.
AB  - Like other herpesviruses, Epstein-Barr Virus (EBV) persists in its host through
      an ability to establish latent infection with episodic reactivations. In latent
      infection EBV expresses an integral membrane protein LMP2A that regulates
      reactivation from latency. LMP2A is constitutively tyrosine phosphorylated and is
      associated with lyn and syk tyrosine kinases. The activity of lyn is
      substantially reduced. In EBV-infected cells in which LMP2A is expressed,
      crosslinking of sIg fails to trigger the protein tyrosine kinase signal cascade,
      tyrosine phosphorylation of cell proteins does not change, second messengers are
      not generated, and lytic EBV infection is not induced. In contrast, crosslinking
      of sIg on cells infected with EBV recombinants with null mutations in LMP2A
      results in transient tyrosine phosphorylation of lyn, syk, phospholipase C gamma
      2 and phosphatidylinositol-3' kinase, transiently increased intracellular free
      calcium, and reactivation of lytic EBV infection. These studies describe a novel
      molecular regulator of herpesvirus latency and focus attention on the importance
      of transmembrane signal transduction in herpes virus reactivation from latency.
      They support the working hypothesis that the identification of ligand-receptor
      interactions that can result in the induction of reactivation will provide an
      important inroad toward the delineation of the molecular mechanism, which govern
      herpesvirus reactivation from latency.

PMID- 7812652
TI  - Molecular piracy of chemokine receptors by herpesviruses.
AB  - To succeed as a biological entity, viruses must exploit normal cellular functions
      and elude the host immune system; they often do so by molecular mimicry. One way
      that mimicry may occur is when viruses copy and modify host genes. The best
      studied examples of this are the oncogenes of RNA retroviruses, but a growing
      number of examples are also known for DNA viruses. So far they all come from just
      two groups of DNA viruses, the herpesviruses and poxviruses, and the majority of
      examples are for genes whose products regulate immune responses, such as
      cytokines, cytokine receptors, and complement control proteins. This review will
      focus on human and herpesvirus receptors for chemokines, a family of leukocyte
      chemoattractant and activating factors that are thought to be important mediators
      of inflammation. Although the biological roles of the viral chemokine receptor
      homologues are currently unknown, their connection to specific sets of chemokines
      has suggested a number of possible functions.

PMID- 7812654
TI  - Current frontiers in virology.

PMID- 7812653
TI  - Immune recognition of viral antigens.
AB  - The response exhibited by the immune system to viral and other foreign antigens
      consists of antibody-mediated and T cell-mediated immunity. Structural and
      molecular biological studies have shown that the antibody response is tailored to
      provide exquisite specificity by generating binding pockets that are
      complementary in shape as well as in charge to the antigen. On the other hand,
      the cellular response uses T-cell receptors (TCRs) and the major
      histocompatibility complex (MHC) antigens. Structural information on the TCRs is
      not yet available, but the crystal structures of several MHC class I molecules
      have shown how one MHC molecule can bind many different peptide sequences that
      share only the common anchor residue positions that determine allele specificity.
      MHC class I interactions with the peptide backbone at the N and C termini explain
      the high specificity of the binding groove for peptide ligands and suggest a
      universal mode of recognition for peptides to MHC class I molecules. Peptide-MHC
      class II interactions are less well understood, although recent structural work
      has shown important differences in the binding clefts of MHC class I and II that
      lead to longer peptides being bound to class II molecules. Detailed analysis at
      the molecular level has indicated that conformational changes in both antibodies
      and MHC molecules occur upon antigen binding.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7812655
TI  - Prion protein and the scrapie agent: in vitro studies in infected neuroblastoma
      cells.
AB  - The mouse neuroblastoma cell line N2a was persistently infected with the Chandler
      strain of the mouse scrapie agent. Although the infection did not spread to
      infect > 1% of the cells, clones were established that had from 50 to 100%
      infected cells. These clones expressed the abnormal protease-resistant form of
      prion protein (PrP), which is believed to mediate brain degeneration in animals
      with scrapie and bovine spongiform encephalopathy and in humans with kuru,
      Creutzfeldt-Jakob disease, and Gerstmann-Straussler-Scheinker syndrome. With this
      in vitro system, Congo red and several sulfated polysaccharides, including
      heparin and pentosan polysulfate, were found to inhibit accumulation of protease
      resistant PrP. These results and additional data confirming PrP binding to
      heparin suggested a possible role for sulfated glycosaminoglycans in the
      generation of protease-resistant PrP during scrapie infection. Accumulation of
      protease-resistant PrP was also blocked in vitro by expression of foreign PrP
      molecules, indicating that PrP from different species might compete for common
      substrates in this process. These results using scrapie-infected cell lines
      provide new opportunities for development of drugs capable of blocking the brain
      degeneration caused by scrapie and other transmissible spongiform
      encephalopathies.

PMID- 7812656
TI  - Properties of an HSV-1 regulatory protein that appears to impair host cell
      splicing.
AB  - The herpes simplex virus type 1 (HSV-1) immediate early (alpha) protein ICP27 is
      an essential regulatory protein that appears to be involved in a number of
      different processes during lytic viral infection. Viral mutants defective in
      ICP27 have a variety of phenotypes that include defects in the shutoff of host
      protein synthesis, overexpression of some immediate early and early genes,
      reduced levels of DNA replication, and severely reduced levels of late gene
      products. ICP27 has been shown to act posttranscriptionally in the performance of
      some of its regulatory roles. It affects mRNA processing at the level of both
      polyadenylation and splicing. During polyadenylation, ICP27 appears to stimulate
      3' RNA processing at selected poly(A) sites. The opposite effect, occurs on host
      cell splicing, that is, during HSV-1 infection, an inhibition in host cell
      splicing was found that required ICP27 expression. This impairment of splicing
      contributes to the shutoff of host protein synthesis by decreasing levels of
      spliced cellular mRNAs available for translation. A redistribution of splicing
      factors regulated by ICP27 has also been seen. Mutational analysis has shown that
      the C-terminal repressor region of the protein is required for the effects seen
      on splicing, whereas the activator region, encompassing the C-terminal half of
      the protein is required for the effects on 3' processing and the induction of
      late gene expression during viral infection. A highly basic arginine-rich region
      in the N-terminal half of the protein is required for nuclear localization of
      ICP27. Details on the mechanisms by which ICP27 contributes to these regulatory
      processes have been poorly defined to date.

PMID- 7812657
TI  - RNA-sequence-mediated gene regulation in HIV-1.
AB  - The quantity and quality of human immunodeficiency virus type 1 (HIV-1) gene
      expression is controlled in large part by the action of two small nuclear viral
      regulatory proteins termed Tat and Rev. Tat is unique among transcriptional trans
      activators in that it acts via a structured RNA target sequence, termed TAR, to
      induce high levels of transcription from the HIV-1 long terminal repeat promoter
      element. The activity of the viral Rev protein is also unprecedented in that this
      protein functions to induce the nuclear export of a specific class of viral RNA
      species that are otherwise sequestered in the nucleus by the action of cellular
      factors. Like Tat, Rev also interacts with a highly specific cis-acting target
      sequence termed, in this case, the Rev Response Element. In this review, I
      provide an outline of our current understanding of the roles and mechanisms of
      action of these two novel RNA-sequence-dependent regulatory proteins.

PMID- 7812658
TI  - Cis-acting signals and trans-acting factors involved in influenza virus RNA
      synthesis.
AB  - Influenza A virus RNA replication and expression is directed from cis-acting
      sequences present on the viral RNAs with the help of trans-acting factors encoded
      by the virus. Ribonucleoprotein (RNP) complexes reconstituted from synthetic cDNA
      derived RNA and purified viral proteins have facilitated the dissection of these
      cis-acting signals and trans-acting factors. Prior to these studies influenza
      viruses and other negative-strand RNA viruses were refractory to molecular
      genetic manipulations. These reverse genetic studies have helped in defining the
      promoter and polyadenylation signals required for viral RNA synthesis. Studies
      involving the use of reconstituted RNP complexes have revealed that the viral
      proteins PB1, PB2, PA, and the nucleoprotein (NP) are necessary for replication
      and expression of influenza virus RNA. Inroads have also been made in determining
      the cellular proteins that participate in influenza virus gene expression and
      replication. The yeast interactive trap system has been used to identify and
      clone a gene (NPI-1), which encodes a protein that interacts with the influenza
      virus NP suggesting that this cellular protein is a trans-acting factor
      functioning in viral RNA synthesis.

PMID- 7812659
TI  - Pathogenesis associated with replication of hepatitis delta virus.
AB  - Hepatitis delta virus (HDV) is a subviral satellite of human hepatitis B virus
      (HBV). HDV was discovered in patients chronically infected with HBV who had a
      more severe form of disease. Subsequent studies have attempted to understand the
      cytopathic effects due to HDV, and this article reviews the progress along with
      newer studies that suggest that HDV genome replication per se causes no more than
      a moderate inhibition of cellular growth rate. This inhibition nevertheless
      provides a selective pressure for reduced levels of HDV genome replication. Such
      a reduction is apparently achieved by a host cell activity that edits the HDV RNA
      genome.

PMID- 7812660
TI  - Coronavirus: how a large RNA viral genome is replicated and transcribed.
AB  - Coronaviruses are important human and animal pathogens and contain an
      extraordinarily long (27-31 kb) RNA genome. Its RNA synthesis involves complex
      mechanisms of regulation, similar to those of DNA viruses. In this treatise,
      mouse hepatitis virus (MHV) is used as a model for the discussion of the
      mechanism of viral RNA synthesis. We show that MHV RNA synthesis requires
      interactions of multiple RNA components, which are likely mediated by protein-RNA
      and protein-protein, as well as RNA-RNA, interactions. This virus also provides a
      unique example of a discontinuous transcription mechanism, which involves a trans
      acting RNA component. Finally, study of the cis-acting signals for the various
      steps of RNA synthesis revealed an insight into the regulation of viral RNA
      synthesis. This discussion suggests that the regulation of RNA synthesis in
      coronavirus is more complex than previously thought possible for RNA viruses.
      Coronavirus RNA transcription and replication may serve as a paradigm of RNA
      synthesis for RNA viruses in general.

PMID- 7812661
TI  - Strategies for inhibition of tumor necrosis factor in vivo.

PMID- 7812662
TI  - Plant-virus movement: de novo process or redeployed machinery?

PMID- 7812663
TI  - Role of outer membrane architecture in immune evasion by Treponema pallidum and
      Borrelia burgdorferi.
AB  - Combined ultrastructural and molecular studies have revealed that the syphilis
      and Lyme-disease spirochetes, Treponema pallidum and Borrelia burgdorferi, have
      distinctive molecular architectures. Both organisms persist in their hosts and
      have strategies for immune evasion that include the use of rare, poorly
      immunogenic surface-exposed proteins as potential virulence determinants.

PMID- 7812664
TI  - Signalling strategies for nodulation of legumes by rhizobia.
AB  - During the formation of nitrogen-fixing root nodules, the establishment of the
      symbiotic relationship between rhizobia and leguminous plants depends on a highly
      specific exchange of signals. The products of several of the rhizobial nodulation
      (nod) genes are involved in the biosynthesis of host-specific lipo
      oligosaccharide signalling molecules that can induce nodule morphogenesis on
      legume roots. Such signalling may point to a more widespread cell-to-cell
      signalling system in plants.

PMID- 7812665
TI  - Integration of antimicrobial host defenses: role of the bactericidal/permeability
      increasing protein.
AB  - Our understanding of the complex and integrated host-defense systems against
      microbial infection has progressed rapidly with the characterization of
      individual components. However, the various factors must be studied not only in
      isolation, but also in a closer approximation to the in vivo situation, where
      these factors interact. This is well illustrated in recent studies of the role of
      the bactericidal/permeability-increasing protein.

PMID- 7812666
TI  - Role of bacteria-specific T cells in the immunopathogenesis of reactive
      arthritis.
AB  - Reactive arthritis is a usually self-limited sterile inflammation of joints that
      follows certain bacterial gastrointestinal or urogenital infections. The
      immunopathogenesis involves CD4+ T cells, which mediate an antigen-specific TH1
      response to bacterial constituents within the joint. Properties of the
      arthritogenic bacteria and the physicochemical characteristics of the bacterial
      antigens may contribute to the development of reactive arthritis.

PMID- 7812667
TI  - A retroviral implication in multiple sclerosis?
AB  - The etiology of multiple sclerosis (MS) is still unexplained. Epidemiological
      studies indicate that environmental agents are involved, and MS shares both
      clinical and histopathological features with retrovirus-mediated neurological
      diseases in animals and humans. Thus, combining the fields of microbiology and
      epidemiology may throw new light on the many unanswered questions posed by MS.

PMID- 7812668
TI  - Bovine tuberculosis: does badger culling help?

PMID- 7812669
TI  - Cyclic or linear conformations of sequences binding lipid A: does it really
      matter?

PMID- 7812670
TI  - Individual differences in mental imagery experience: developmental changes and
      specialization.
AB  - This research has two purposes: (1) to study developmental changes and
      differences in visual and movement imagery in male and female children and
      adults; (2) to investigate whether systematic differences in imagery vividness
      can be measured in specialist groups. In Study 1, the Vividness of Visual Imagery
      Questionnaire and the Vividness of Movement Imagery Questionnaire were
      administered to 547 individuals in age groups from 7-8 to 50+ years of age.
      Significant increases in imagery vividness were found in females at 8-9 and in
      males at 10-11 years. In general females report more vivid imagery than males but
      at about 50 females' movement imagery reduced in vividness. In Studies 2-5
      imagery differences in specialist groups were examined using the same two
      questionnaires with a total of 655 participants. In Study 2, children aged 7-15
      years with poor movement control were found to be extremely poor imagers with 42
      per cent reporting no imagery at all. In Study 3, physical education students
      reported more vivid imagery than students specializing in physics, English, and
      surveying. In Study 4, significant differences were found between elite athletes'
      imagery and that of matched controls. In Study 5, air traffic controllers and
      pilots were found to have significantly more vivid imagery than matched control
      groups. Introspective reports of imagery experience show a systematic pattern of
      relationships with age, gender, and specialization requiring high-level
      performance of perceptual motor skills. These findings support the theory that
      mental imagery plays a key role in the planning and implementation of action.

PMID- 7812671
TI  - Self-reported fears to common indigenous animals in an adult UK population: the
      role of disgust sensitivity.
AB  - Two studies are described which report on the prevalence and intensity of self
      reported fears to common indigenous animals in an adult UK population. The
      results of Study 1 suggest that (i) around a third of the variance in fear of
      indigenous animals can be accounted for by two factors which represent the
      theoretically coherent categories of invertebrates (e.g. slug, worm, cockroach)
      and fear-relevant animals (e.g. rat, snake, bat); (ii) females tend to report
      significantly greater levels of fear than males to a large majority of
      prevalently feared animals; and (iii) there were no obviously consistent patterns
      of fear with age. Study 2 identifies individual disgust sensitivity levels as
      being an important and significant predictor of fear of animals in both the
      invertebrate and fear-relevant categories, and finds that females report
      significantly higher disgust sensitivity levels than males. Since most of the
      prevalently feared indigenous animals appear to be disgust-relevant, this latter
      finding helps to explain the generally higher fear ratings given by females.

PMID- 7812672
TI  - Effects of low-density lipoproteins on polymorphonuclear leukocyte functions in
      vitro.
AB  - In the circulation, human polymorphonuclear leukocytes (PMN) are exposed to
      various factors, such as lipoproteins, which could alter their metabolic and
      functional characteristics. In this work, the effects of low-density lipoproteins
      (LDL) on PMN oxidative metabolism and migration were studied in vitro. LDL
      stimulated PMN superoxide generation. This effect lasted for 15-20 min and was
      concentration-dependent. Staurosporine, a potent inhibitor of protein kinase C,
      did not suppress this stimulating effect. The chemotactic response of PMN to
      formyl-methionyl-leucyl-phenylalanine and C5a was inhibited by LDL and this
      effect was conserved after trypsination of LDL. LDL from normolipidemic subjects
      were more potent than LDL from hypertriglyceridemic subjects for both effects.
      LDL had no effect on superoxide generation by opsonized zymosan-stimulated PMN.
      These data showed that PMN responses may be modified by environmental conditions
      such as the presence of lipoproteins.

PMID- 7812673
TI  - Phorbol ester-induced dermal inflammation in mice: evaluation of inhibitors of 5
      lipoxygenase and antagonists of leukotriene B4 receptor.
AB  - In the present investigation, the effects of selective inhibitors of 5
      lipoxygenase (5-LO), zileuton and TZI-41127, E-6080, AA-861 and antagonists of
      leukotriene B4 (LTB4) receptors, SC-41930, and SC-51146 and a selective
      cyclooxygenase inhibitor, indomethacin, were examined in TPA-induced acute mouse
      dermal inflammation. Topical application of all these agents, except
      indomethacin, resulted in marked attenuation of TPA-induced edema and influx of
      neutrophils reflected in myeloperoxidase measurements. Topically applied SC-41930
      attenuated TPA-induced edema and neutrophil influx in a dose-related manner. Oral
      administration of LTB4 receptor antagonists either as a pre-treatment or post
      treatment attenuated TPA-induced edema and influx of neutrophils. The O-demethyl
      analog of SC-41930, SC-37920, which was nearly 1000-fold less active than SC
      41930 in LTB4 receptor binding assays, was inactive in inflammation assays,
      suggesting a role for LTB4 in this response. Zileuton and TZI-41127 were more
      effective as anti-inflammatory agents following oral administration than after
      i.p. administration. Intraperitoneally administered indomethacin attenuated edema
      response but not influx of neutrophils. Taken together, these results suggest a
      role for leukotrienes in acute inflammation induced by TPA and possible utility
      of this model to test in vivo 5-LO inhibitors and LTB4 receptor antagonists.

PMID- 7812674
TI  - The effect of SRI 63-675, a competitive platelet-activating factor receptor
      antagonist, in the generalized Shwartzman reaction.
AB  - Evidence indicates a role for platelet-activating factor (PAF) in endotoxin (LPS)
      induced shock. To determine its involvement in LPS-induced intravascular
      coagulation, we assessed the efficacy of SRI 63-675, a specific PAF receptor
      antagonist, to prevent fibrin deposition in the various organs of New Zealand
      White rabbits 4 h after two intravenous doses of LPS (100 micrograms/kg), spaced
      24 h apart. SRI 63-675 significantly lowered peak tumor necrosis factor levels
      after LPS challenge. Administration of SRI 63-675 around either the first (150
      mg/kg) or second LPS dose (120 mg/kg), however, did not prevent coagulation. The
      unexpected high mortality after combined administration of SRI 63-675 and LPS
      precluded assessment of PAF inhibition around both LPS doses on coagulation. Sole
      administration of SRI 63-675 induced rapid and transient changes in peripheral
      blood cell counts, and blood pressure and heart rate suggestive of intrinsic PAF
      like activity. Although some other intrinsic toxic effect of SRI 63-675 cannot be
      ruled out, it is suggested that endotoxin may have primed the rabbit to the
      lethal, PAF-like, effects of SRI 63-675.

PMID- 7812675
TI  - A 15-nonstereogenic carbocyclic analogue of prostacyclin: effects on human
      platelets and uterine artery.
AB  - Platelet-suppressant and vasodilator effects of the (+) enantiomer of 13,14
      dihydro-15,16,17,18,19,20-hexanor-14-(1-hydroxycyclohexyl)++ +carbocyclin
      (MM706), a carbocyclic analogue of prostacyclin with the 15-hydroxyl group
      located at a symmetrically substituted carbon atom were studied on human
      platelets and isolated uterine artery. In washed platelets it inhibits platelet
      aggregation with an IC50 value of 77 nM as compared to IC50 = 1.3 nM for PGI2. In
      the presence of indomethacin its potency like that of PGI2 decreases about 2
      fold. Also, MM706 like PGI2 fails to inhibit the norepinephrine (NE)-stimulated
      contractions of isolated human uterine artery in the absence of indomethacin.
      Pretreatment of the artery with indomethacin (3 microM) makes it sensitive to
      both MM706 and PGI2, the EC50 values being 99 and 3.1 nM, respectively. The
      results show that MM706 is an effective inhibitor of platelet aggregation and NE
      stimulated contractions of the indomethacin-treated uterine artery.

PMID- 7812676
TI  - Pharmacological profile of UK-74,505, a novel and selective PAF antagonist with
      potent and prolonged oral activity.
AB  - UK-74505, a novel 1,4-dihydropyridine PAF antagonist, exhibited highly selective,
      time-dependent inhibition of PAF-induced aggregation of rabbit washed platelets
      (IC50 = 26.3 +/- 0.88 and 1.12 +/- 0.04 nM after 0.25 and 60 min preincubation,
      respectively), which became irreversible within 15 min, whereas inhibition by WEB
      2086 was both independent of preincubation time (IC50 = 145.7 +/- 24.7 nM) and
      competitive (KI = 27.5 +/- 7.7 nM; Schild slope = 0.98 +/- 0.04). The selective
      inhibition of specific [3H]PAF binding by UK-74,505 exhibited a slower onset, the
      IC50 obtained without preincubation (14.7 +/- 2.6 nM) decreasing 2-fold at 45
      min. UK-74,505 was 450-fold weaker as an antagonist of [3H]nitrendipine binding
      to bovine brain membranes and KCl-induced contraction of rat aorta. UK-74,505 was
      10-30-fold more potent than WEB-2086 in vivo as an inhibitor of PAF-induced
      hypotension in rats (ED50 = 35 +/- 5.8 micrograms/kg, i.v.), cutaneous vascular
      permeability in guinea pigs (ED50 = 0.37 +/- 0.08 mg/kg, p.o.) and lethality in
      mice, with oral ED50 values of 0.26 +/- 0.03 and 1.33 +/- 0.19 mg/kg at 2 and 8
      h, respectively. These data demonstrate that UK-74,505 is a potent, selective,
      long-acting irreversible PAF antagonist.

PMID- 7812677
TI  - Role for Ca2+ in expression of cell cycle regulated genes in PAF-stimulated
      cells.
AB  - Platelet-activating factor (PAF) is a powerful stimulator of a wide variety of
      cells. In transformed human B-lymphoblastoid cell lines, PAF increases
      intracellular Ca2+ concentrations ([Ca2+]i) and induces the expression of the
      proto-oncogenes c-fos and early growth response gene-2 (EGR2). Here, we present
      data that evaluates the role of Ca2+ in the PAF-dependent induction of these cell
      cycle activated genes. PAF (10(-7) M) increased c-fos and EGR2 mRNA levels in
      cells suspended in Ca(2+)-containing medium by 6-10-fold. In PAF-stimulated cells
      suspended in medium depleted of Ca2+, eliminating Ca2+ influx but not
      intracellular store release of Ca2+, the induction of gene expression was reduced
      by approx. 50%. In contrast, buffering of Ca2+ released from intracellular stores
      but maintaining transmembrane Ca2+ uptake had little effect on gene expression.
      When both sources of Ca2+ were eliminated, PAF-stimulated expression of these
      genes was completely prevented. This was not due to any toxicity to the cells
      since the response to phorbol ester under identical conditions was unaffected.
      The regulation of c-fos mRNA expression was paralleled by changes in levels of
      FOS protein. These data indicate that changes in [Ca2+]i, primarily from
      stimulated entry across the plasma membrane and to a lesser extent release of
      Ca2+ from sequestered intracellular stores, play an essential role in PAF
      dependent triggering of c-fos and EGR2 mRNA expression.

PMID- 7812678
TI  - Regulation of lipopolysaccharide-induced tumor necrosis factor alpha production
      by endogenous prostaglandin E2 in rat resident and thioglycollate-elicited
      macrophages.
AB  - Prostaglandin E2 (PGE2) is generally accepted to be a negative feedback effector
      of tumor necrosis factor alpha (TNF alpha) production. However, we have observed
      that a cyclooxygenase inhibitor had different effects on TNF alpha production by
      resident and thioglycollate-elicited rat peritoneal macrophages. Indomethacin
      coordinately reduced PGE2 production and increased TNF alpha production in
      lipopolysaccharide (LPS)-stimulated resident macrophages, whereas indomethacin
      reduced PGE2 production without affecting TNF alpha production in thioglycollate
      elicited macrophages. PGE2 production and arachidonate release were much less in
      thioglycollate-elicited macrophages than in resident macrophages. However,
      exogenously added PGE2 suppressed TNF alpha production to the same extent in the
      two macrophage populations. The addition of free arachidonic acid to cultures of
      LPS-stimulated, thioglycollate-elicited macrophages elevated PGE2 production and
      suppressed TNF alpha production in a manner similar to that observed with LPS
      stimulated resident macrophages. These results indicate that the differential
      effects of indomethacin treatment on TNF alpha production observed between the
      two macrophage populations are not due to the differences in arachidonate
      contents, PGE2 productivities, nor to their capacities to respond to PGE2.
      Instead, the inability of indomethacin to increase TNF alpha production by
      thioglycollate-elicited versus resident macrophages appears to result from an
      inability to release arachidonate efficiently and a lower initial level of
      cyclooxygenase, in thioglycollate-elicited macrophages.

PMID- 7812679
TI  - Characterization of phospholipase A2 release by elicited-peritoneal macrophage
      and its relationship to eicosanoid production.
AB  - Elicited guinea pig peritoneal macrophages released a soluble phospholipase A2
      (PLA2) into conditioned media that was biochemically and pharmacologically
      similar to the recombinant human (rh) type II 14 kDa PLA2. The level of activity
      found in the 24 h media positively correlated with cell number and was reduced by
      actinomycin D and cycloheximide suggesting the enzyme was being constitutively
      synthesized. The enzyme protein accumulated in the media over 10-24 h and
      remained at maximal levels over 40 h as demonstrated by both activity and ELISA
      measurements. This was preceded by an increase in total cell-associated sn-2
      acylhydrolytic activity which reached maximal levels by 12-17 h of culture and
      remained elevated to 40 h. Treatment of cell homogenate with dithiothreitol (DTT)
      revealed a rise in DTT-insensitive sn-2-acylhydrolytic activity which increased
      between 12 and 24 h. Prostaglandin (PG) E2 but not leukotriene (LT)B4 accumulated
      in the media and reached maximal levels by 24 h. This paralleled the release of
      secreted type II 14 kDa-like PLA2 and the rise in DTT-insensitive cell-associated
      activity, but not upregulation and formation of new cyclooxygenase after aspirin
      treatment. Overnight exposure to a non-cell permeable selective 14 kDa PLA2
      inhibitor or neutralizing mAb interfered with expression of PLA2 activity but not
      PGE2 accumulation over 24 h. This indicated that the secreted PLA2 was not
      directly involved in PGE2 biosynthesis. Exposure of the elicited macrophages to
      the cell permeable 14 kDa PLA2 inhibitor, 12-epi-scalaradial also did not effect
      PGE2 accumulation. Taken together, elicited guinea-pig macrophages release 14 kDa
      PLA2 upon culture, but this activity appears not to be related to the concomitant
      accumulation in PGE2. The role of the cell-associated PLA2 activity(s) in PGE2
      formation cannot be ruled out.

PMID- 7812680
TI  - Biochemical and pharmacological comparison of a cytosolic, high molecular weight
      phospholipase A2, human synovial fluid phospholipase A2 and CoA-independent
      transacylase.
AB  - We have compared biochemical and pharmacological characteristics of CoA
      independent transacylase (CoA-IT) activity of microsomes from U937 cells to those
      of two other enzymes involved in arachidonate metabolism, a human type II low
      molecular weight (M(r) 14,000, LMW) PLA2 isolated from synovial fluid of patients
      with inflammatory joint disease and a high molecular weight (M(r) 85,000, HMW)
      PLA2 enzyme isolated from the cytosol of human monocytic U937 cells. Activities
      of HMW PLA2 and CoA-IT were reduced by treatment with acid, heat or acetonitrile
      but were not altered by treatment with the sulfhydryl reducing agent
      dithiothreitol (DTT). In contrast, the activity of LMW PLA2 enzyme was
      inactivated by DTT, but was insensitive to treatment with acid, heat or
      acetonitrile. HMW PLA2 activity decreased as NaCl concentration was increased in
      the assay buffer from 0 to 150 mM, unlike LMW PLA2 and CoA-IT activities, which
      increased as NaCl increased. Compounds that inhibit LMW PLA2 activity were
      examined for their effects on HMW PLA2 and CoA-IT activities. The compounds
      examined (nordihydroguaiaretic acid, manoalide, p-bromophenacyl bromide,
      arachidonic acid, gossypol, aristologic acid and a mimic of a transition state
      phospholipid) had different rank orders for inhibition of the three enzymes.
      Taken together, these data show that these three enzymes, although unpurified,
      can be biochemically and pharmacologically distinguished.

PMID- 7812681
TI  - Homologous desensitization of PAF receptors via a PGE2-dependent pathway on
      intestinal smooth muscle.
AB  - The aim of the present study was to evaluate the effect of in vitro preincubation
      with PAF of isolated smooth muscle cells from guinea pig ileum in order to assess
      possible PAF receptor desensitization. Cells dispersed by enzymatic digestion
      were preincubated with PAF for 30 min and the contractile effect of PAF was then
      assayed. In cells preincubated for 30 min with 10 nM PAF, the concentration
      inducing maximal cell contraction was 1 microM instead of 10 nM in freshly
      dispersed cells and the EC50 was 40 nM instead of 10 pM. This desensitization to
      the contractile effect of PAF was prevented when cells were preincubated for 30
      min with PAF plus PAF antagonist BN52021, PGE2 antagonist SC19220, cyclooxygenase
      inhibitor indomethacin and the phospholipase A2 inhibitor bromophenacyl bromide.
      In similar experiments, no desensitization occurred for CCK8 receptors after
      preincubation with either PAF, PGE2 or CCK8. These results indicate that
      homologous desensitization of PAF receptors could occur via a PGE2-dependent
      pathway in intestinal smooth muscle cells from guinea pig.

PMID- 7812682
TI  - The effect of RP 59227, a platelet-activating factor antagonist, against antigen
      challenge and eosinophil and neutrophil chemotaxis in asthmatics.
AB  - STUDY OBJECTIVES: Platelet-activating factor (PAF), an inflammatory mediator,
      induces microvascular leak, eosinophil chemotaxis, and possibly increases non
      specific bronchial hyperresponsiveness in humans. PAF antagonists may have
      clinical benefits in asthma. DESIGN: We determined the safety and efficacy of a
      240 mg oral dose of RP-59227 in attenuating the early and late phase antigen
      challenge in eight asthmatics, using a double-blind, placebo-controlled,
      crossover design. Also determined was the effect of the ex vivo addition of PAF
      following placebo or drug and the level of neutrophil (NCA) and eosinophil
      chemotactic activity (ECA) in the serum immediately, and 4 h after antigen
      challenge with either drug or placebo. RESULTS: There was not a significant
      difference in the maximum percent fall in FEV1 during the early and late phase on
      screening or placebo days or drug RP-59227 days. There was a significant
      inhibitory effect (p < 0.05) in peak ECA and NCA in blood after RP-59227. The
      addition of PAF to ex vivo serum was less effective in inducing chemotaxis to
      eosinophils following RP-59227 (p < 0.05). CONCLUSIONS: RP-59227 attenuated the
      release of NCA and ECA after antigen challenge, and reduced the effect of
      exogenously added PAF in inducing eosinophil chemotaxis but did not protect
      against the antigen-induced early or late phase response.

PMID- 7812683
TI  - Medical waste disposal. Medical Waste Committee (WT-3). Technical Council Air &
      Waste Management Association.
AB  - Medical (biomedical) wastes pose numerous potential health and safety hazards. In
      addition to their infectious and toxic characteristics, the highly variable and
      inconsistent nature of medical waste streams has increased public concern about
      storage, treatment, transportation, and ultimate disposal. In recent years,
      techniques have been developed to reduce human exposure to the toxic and
      infectious components of medical wastes. The most commonly used techniques
      include internal segregation, containment, and incineration. Other common
      techniques include grinding, shredding, and disinfection, e.g., autoclaving and
      chemical treatment followed by landfilling. Of all the available technologies for
      medical waste treatment and disposal, incineration has been found to be the most
      effective method overall for destroying infectious and toxic material, volume
      reduction, and weight reduction in the medical waste stream. Incineration
      destroys the broadest variety of medical waste constituents and can recover
      energy from the medical waste stream. Incineration also is an appropriate
      alternative to burial of human pathological remains.

PMID- 7812684
TI  - An inversion algorithm for determining area-source emissions from downwind
      concentration measurements.
AB  - Measuring emissions from nonuniform area sources, such as waste repository sites,
      has been a difficult problem. A simple but reliable method is not available. An
      objective method of inverting downwind concentration measurements, utilizing an
      assumed form of atmospheric dispersion to reconstruct total emission rate and
      distribution, is described in this study. The Gaussian dispersion model is
      compared to a more realistic model based on K-theory and similarity expressions.
      A sensitivity analysis is presented indicating the atmospheric conditions under
      which a successful application of the method could be anticipated. Field releases
      of sulfur hexafluoride (SF6) from a simulated area source in flat terrain were
      conducted to check the method, ability to reconstruct source distribution, and
      total emission rate. The sensitivity analysis and the field study confirm that a
      few ground-level concentration measurements and a simple determination of the
      atmospheric dispersion characteristics are sufficient, under neutral to stable
      conditions, to obtain the total emission rate accurately. Reconstruction of the
      spatial pattern of the source is possible by utilizing concentration information
      from samplers located on two separate ground-level receptor lines, if a shift in
      the wind direction occurs and if it can be assumed that the total emission rate
      is time invariant. A method of cross-checking the accuracy of the reconstruction,
      using a simultaneous tracer release, is presented.

PMID- 7812685
TI  - [25 years of the Pharmacy School of Charles University in Hradec Kralove].

PMID- 7812686
TI  - [The basis and goals of the pharmacy profession--pharmacobotany and its
      contribution to the development of drugs].
AB  - Pharmacy is one of very comprehensive and complex fields of human activity; the
      interrelationships of its individual principal disciplines did not always develop
      synergically in the course of time. At present, when the field commemorates
      important anniversaries and develops in the period of new social changes, it is
      necessary to contemplate the development of the individual fields and their
      balances in the principal entity for the pharmacist--the medicament. The
      historiography of the field unambiguously points at the cardinal position of
      classic pharmacognosy in this process, showing its development, separation of
      pharmacology, the relationship of pharmacognosy to pharmaceutical chemistry, the
      differences between the two disciplines and the origin of galenical pharmacy, or
      the not very fortunate concept of biopharmaceutics. This process takes place in
      the picture of the dialectical unity of the principal pharmaceutical categories:
      the drug--the pharmaceutical preparation--the medicament. The development of
      pharmacobotany as a practical complex discipline originated from pharmacognosy
      shows in a graphic way the development of the discipline "an sich" into the
      entity "fur sich" and suggests the approach of the pharmacist to the phenomenon
      of the medicament from the historiographical viewpoint.

PMID- 7812687
TI  - [CADISO (Cardiovascular Diseases and Stability of the Organism): 10 years of
      integrated research on natural substances at the Charles University Pharmacy
      School in Hradec Kralove].
AB  - The research project CADISO (Cardiovascular Diseases and Stability of the
      Organism--Phytotherapeutical Possibilities) is an alliance board associating
      approximately 20 professional institutions, its centre and coordinating
      laboratory being the Department of Pharmaceutical Botany and Ecology, Faculty of
      Pharmacy, Charles University, Hradec Kralove. It aims at the prevention
      (additives in food industry) and therapy of diseases of the circulatory apparatus
      using phytotherapeutic agents and substances isolated from higher plants and
      fungi. The project is divided into three systems of investigation: ADAPRETE, i.e.
      the substances increasing the nonspecific resistance of the organism (adaptogenes
      of plant origin, immunostimulants), DIACORD, dealing with the substances acting
      on the cardiovascular system in a mediated way, i.e. treating the diseases the
      eventual action of which alters the heart and vessels (antihypercholesterolemics,
      antihyperlipidemics, antidiabetics, anti-oxidants and quenchers of free radicals,
      hepatoprotectives, anti-aggregating agents), and CORCORAN studying the taxons and
      substances isolated from them which act directly on the circulatory system
      (cardiotonic, anti-arrhythmic and vasodilating agents). To achieve a real purpose
      of the project, the linking-up of the phytochemical, pharmacological
      toxicological, pharmaceutical-technological fields, production of raw materials
      and legislation is ensured.

PMID- 7812688
TI  - [Phytotherapeutic aspects of diseases of the circulatory system. III. Cardiotonic
      and cardiotoxic effects of hyrcanoside and deglucohyrcanoside isolated from
      Coronilla varia L].
AB  - The Cardiotonic and cardiotoxic effects of two cardiac glycosides-hyrcanoside and
      deglucohyrcanoside-isolated from the seeds of Coronilla varia L. were evaluated
      in the paper--in comparison with the effect and toxicity of digoxin and ouabain.
      Evaluation of the cardiotonic effect using the methods of heart "in situ" and the
      isolated heart (Langendorff) proved that deglucohyrcanoside is more effective
      than hyrcanoside and that its effect is equal to that of digoxin as well as
      ouabain. The efficacy of deglucohyrcanoside et least to that of digoxin, while
      the toxicity of the former is several times lower, makes the glycoside a
      potential candidate for therapeutic use.

PMID- 7812689
TI  - [Cardiotoxicity of a selected group of drugs].
AB  - Drugs and other chemical substances can impair the heart in any of its functions-
      electrical activity, mechanical activity and metabolism, most frequently by a
      graded pharmacological action or a direct toxic effect, or immunological
      mechanisms (hypersensitive reaction). The drugs with the potentially greatest
      cardiotoxic effect on the function of the heart include beta 1-sympathomimetics,
      beta 1-blockers, cardiac glycosides, antidysrhythmics, inhalational general
      anaesthetics, methylxanthine, and anthracycline cytostatics. Other drugs, which
      are mainly of toxicological importance and which can act cardiotoxically, are
      halogenated hydrocarbons, ethanol, nicotine and heavy metals. A knowledge of the
      cardiotoxic action of the above-mentioned groups of drugs is essential for their
      safe use in clinical practice.

PMID- 7812690
TI  - [Social pharmacy in pharmacy education].
AB  - Social pharmacy as the only pharmaceutical interdisciplinary field deals in its
      full scope with the problems of pharmacy und medicines in society. The paper
      presents the definition of the field and the scope of problems concerned both in
      teaching and research. The development in the Czech Republic and further
      prospects of the field in the education of pharmacists in the Czech Republic with
      regard to the current trends in the world are discussed.

PMID- 7812691
TI  - Antibody-targeted drugs for the therapy of cancer.
AB  - The advent of monoclonal antibodies has revitalised the concept of magic bullets
      and various agents (eg. drugs, toxins and isotopes) have been conjugated to
      monoclonal antibodies for selective delivery to tumours. Preclinical studies in
      mouse tumour models have been impressive and have lead to several clinical
      trials. These phase I trials have been less impressive. However, keeping in mind
      the aim of Phase I trials, the safety of using these conjugates in humans have
      been established. Several, major problems still remain to be overcome before
      these agents may be useful for the treatment of cancer. These problems stem from
      the nature of tumour vasculature, cytotoxic activity of the moiety linked to
      antibody and the targeted tumour antigen expressed on the cell surface. This
      review will deal with these various aspects described above and possible
      approaches to overcome these obstacles with a definite bias towards drug
      monoclonal antibody conjugates. However, these concepts are equally applicable
      for improved targeting of other agents.

PMID- 7812692
TI  - A novel chemical approach to drug delivery: lipidic amino acid conjugates.
AB  - A novel infinity-amino acid based oligopeptide system has been designed, which
      combines structural features of lipids with those of amino acids and peptides.
      Because of their bifunctional nature, the fatty amino acids and peptides have the
      capacity to be chemically conjugated to drugs and peptides with a wide variety of
      functional groups. The linkage between drug and lipidic unit may either be
      biologically stable (ie. a new drug is formed) or exhibit biological or chemical
      instability (ie. the conjugate is a pro-drug). In either case, the resulting
      conjugates would be expected to possess a high degree of membrane-like character,
      which may be sufficient to facilitate their passage across membranes. The long
      alkyl side chains may also have the additional effect of protecting a labile
      parent drug from enzymatic attack. The lipidic system has been conjugated to a
      wide variety of different compounds, including (i) alkaloids (ii) beta-lactam
      antibiotics, (iii) anticancer compounds (iv) CNS drugs and (v) peptides. The
      biological examination of the conjugates showed that an increase in lipophilicity
      caused an increase in the in vitro cellular and in vivo oral uptake, as well as
      passage through the blood-brain-barrier, suggesting that conjugation to lipidic
      amino acids and peptides is a useful approach to improve the absorption of poorly
      absorbed drugs. Lipidic conjugates of peptides (TRH, LHRH) resulted in higher
      enzymatic stability of the conjugates, proving that the long alkyl side chains
      also have the additional effect of protecting a labile parent drug or peptide in
      a biological environment. A novel Lipid-Core-Peptide (LCP) system has also been
      synthesised by incorporating lipidic amino acids to a lysine based polyamino acid
      system to enhance lipophilicity and membrane binding effects and the metabolic
      stability of the compound. The LCP system as a combined adjuvant-carrier-vaccine
      greatly increased the immunogenicity of synthetic peptides.

PMID- 7812693
TI  - Targeting drugs to the colon: delivery systems for oral administration.
AB  - The oral delivery of drugs to the colon has applications in a variety of
      therapeutic areas. This review is concerned with the approaches taken to achieve
      a universal system for delivery. The design of such a system requires the
      identification and exploitation of a unique feature of the colonic environment.
      The use of transit times, pH and bacterial enzymes are critically assessed. In
      addition, the system must provide protection for the drug during transit to the
      colon. Upper gastro-intestinal physiology and the transit of pharmaceuticals
      through these regions are reviewed with reference to their relevance in achieving
      site specificity.

PMID- 7812694
TI  - Membrane modification by negatively charged stearyl-polyoxyethylene derivatives
      for thermosensitive liposomes: reduced liposomal aggregation and avoidance of
      reticuloendothelial system uptake.
AB  - In order to avoid reticuloendothelial system (RES) uptake and prolong systemic
      circulation of cisplatin (CDDP)-encapsulating thermosensitive liposomes,
      stearylpolyoxyethylene (POE) derivatives [SnC, stearyl-O-(CH2CH2O)n-CH2COONa]
      were incorporated as membrane modifiers into lipid bilayers composed of
      dipalmitoylphosphatidylcholine (DPPC) and distearoylphosphatidylcholine (DSPC).
      The incorporation of S2C, S5C, S10C or S15C [lipid/SnC = 10/2 (w/w)] greatly
      reduced liposomal aggregation without impairing liposomal stability. After being
      intravenously administered to rats, the liposomes remained longer in the systemic
      circulation and showed lower RES levels than the control liposomes. When
      incorporated into liposomes [DPPC/DSPC = 7/3 (w/w)], S10C provided the greatest
      increase in systemic circulation time and the RES-avoiding activity among the
      modifiers tested. The systemic elimination rate (the ratio of the percent of the
      dose systemically eliminated to the AUC of the liposome level) for this type of
      liposome was 0.24/hr, about one fourth the rate for the control liposomes, and
      the RES uptake rate (the ratio of the percent of the dose taken up by the RES to
      the AUC) was 0.04/hr, one seventh the rate for the control liposomes. The RES
      uptake rate for S10C 7/3-liposomes was similar to the rate reported for GM1
      liposomes, although the systemic elimination rate was double that for the GM1
      liposomes. The obtained RES avoidance activity can be attributed to decreased
      liposomal aggregation and increased surface hydrophilicity. This type of
      thermosensitive liposome should be more useful in hyperthermia-mediated targeted
      tumor drug delivery systems than the thermosensitive liposomes without the
      modifiers to avoid RES uptake.

PMID- 7812695
TI  - Review of the curative role of radiotherapy in the treatment of non-small cell
      lung cancer.
AB  - The present paper is a comprehensive review of available data concerning the role
      of radiotherapy as an intended curative treatment in patients with non-small cell
      lung cancer (NSCL). The following issues are reviewed (1) optimal dose, (2)
      optimal fractionation, (3) optimal treatment planning, (4) clinical results in
      terms of single treatment and combined treatment with either surgery or
      chemotherapy. In resectable NSCLC high dose radiotherapy to small localized
      tumours gives a 5-year survival rate of 7-38%. It is concluded that this
      treatment modality is appropriate for certain selected patients who refuse to
      have surgery, who have medical contradications for surgery, or who are of old
      age. It is discussed whether the treatment should be split course, continuous,
      hypo-og hyperfraction. A total dose of 55 Gy must be given. CT scanning should be
      mandatory for optimal planning and therapy. The literature does not give a
      conclusive answer to whether preoperative or postoperative radiotherapy is
      indicated. The data indicate that patients with Stage III NSCLC will benefit from
      a combined treatment modality in terms of chemotherapy based on high dose
      cisplatinum and radiotherapy. The main conclusion of the review is that many
      areas with randomized controlled trials are needed in order to answer the
      critical issue of the role of radiotherapy in the treatment of NSCLS.

PMID- 7812696
TI  - Risk factors for lung cancer in Rio de Janeiro, Brazil: a case-control study.
AB  - The association between the risk of lung cancer and tobacco smoking, dietary
      factors and occupational exposures was examined in a hospital-based case-control
      study. The study involved 123 consecutive cases and 123 controls, matched by age
      (+/- 3), sex, and race. In this first study of lung cancer risk in Brazil, we
      found that tobacco smoking is the strongest risk factor with an odds ratio (OR)
      for current and former smokers of 22 (CI, 6.5-76) and 7.7 (CI, 2.2-27),
      respectively. An OR of 2.8 (CI, 1.0-7.7) was found for users of black tobacco in
      the form of hand-rolled cigarettes) in combination with conventional cigarettes,
      after adjustment for life-time consumption of any kind of tobacco; users of
      conventional cigarettes only were considered as a reference group. Cessation of
      smoking had an important influence in reducing the lung cancer risk, whereas
      early initiation of smoking increased the risk. Among dietary factors, frequent
      consumption of meat (P < 0.01) and pasta (P = 0.02) were positively associated
      with lung cancer risk after adjusting for smoking and income. No association was
      found with green/yellow vegetables or fruits. We were unable to detect any
      significant association related to occupational exposures. This study confirmed
      the association of lung cancer with smoking as the most important predictor of
      risk. It also indicates the increase in risk associated with the use of black
      tobacco in combination with conventional cigarettes.

PMID- 7812697
TI  - Smoking of hand-rolled cigarettes as a risk factor for small cell lung cancer in
      men: a case-control study from Uruguay.
AB  - During the time period January 1989-December 1992, a case-control study involving
      476 cases of lung cancer and 561 controls was carried out at the Instituto
      Nacional de Oncologia, Montevideo, Uruguay, in order to analyze the patterns of
      risk of the different cell types of lung cancer, associated with smoking
      manufactured and hand-rolled cigarettes. Lifelong smokers of hand-rolled
      cigarettes displayed a non-significant 30% increased risk, compared with smokers
      of commercial cigarettes, for all types of lung cancer combined. The analysis for
      cell-type disclosed a fourfold increase in the risk of small cell lung carcinoma
      associated with lifelong smoking of hand-rolled products. The possibilities of a
      chance finding and of misclassification of the disease appears to be an unlikely
      explanation of this strong and rather specific association.

PMID- 7812698
TI  - DNA stemline heterogeneity of non-small cell lung carcinomas and differences in
      DNA ploidy between carcinomas and metastatic nodes.
AB  - Nuclear DNA contents were measured using a flow cytometry technique in non-small
      cell lung carcinomas and differences in ploidy patterns were compared between
      primary lung carcinomas and metastatic lymph nodes. Negative node lung cancer
      revealed diploidy in 82.6% of the 224 non-small cell lung cancers, in contrast
      with 19.5% in positive node lung cancer. In multi-stemline cells, a high
      incidence of nodal involvement was seen when compared with single stemline cells.
      The more the DNA indices increased, the more the lymph nodes were seen to be
      extensively involved. Furthermore, intratumoral heterogeneity was evaluated in
      terms of n-categories. In conclusion, it is suggested that nodal metastasis may
      be caused by tumor cells with high DNA indices in lung carcinomas, in particular
      for multi-stemline cells.

PMID- 7812699
TI  - Detection of lymph node metastases in lung cancer: comparison of 131I-anti-CEA
      anti-CA 19-9 immunoscintigraphy versus computed tomography.
AB  - Mediastinal lymph node metastasis is one of the most important prognostic
      variables of lung cancer. We designed a study to compare immunoscintigraphy (IS)
      using iodine-131 anti-carcinoembryonic antigen (CEA) and anti-carbohydrate 19-9
      (CA 19-9) monoclonal antibody and computed tomography (CT-scan), in the setting
      of mediastinal staging. Seventeen patients were involved in a prospective, blind
      study, to compare IS with CT-scan imaging of the mediastinum. Sensitivity and
      specificity of both methods were analyzed with reference to pathological staging
      by mediastinal lymph node sampling. IS imaging was not possible in two patients
      owing to a thyroid uptake and one patient refused surgery. Among the 14 evaluable
      patients, sensitivity and specificity were 0.83 and 0.12 for IS, and 0.66 and
      0.50 for CT-scan, respectively. We used different thresholds of positivity for
      both methods in order to evaluate the sensitivity-specificity relationship. When
      compared with that of IS, the area under the receiver operating characteristic
      (R.O.C.) curves of the CT-scan was bigger. Although one patient had
      pathologically confirmed N2 with negative CT-scan and positive IS, the results of
      IS were hampered by a very high level of false positivity. Finally, there was no
      relationship between positivity of IS and a high serum CEA level. Lack of
      specificity and the insufficient sensitivity of the iodine-131 anti-CEA-anti-CA
      19-9, lead to the conclusion that IS adds weak information to a CT-scan, in the
      non-invasive mediastinal staging of lung cancer. More efficient radionuclides and
      markers are needed in the setting of lung cancer staging.

PMID- 7812700
TI  - Survival of noncuratively resected lung cancer.
AB  - Out of 858 patients who underwent thoracotomy for primary lung cancer, 279 cases
      were classified as non-curative on the basis of intraoperative and/or post
      operative examinations. The causes for non-curative resection were defined as
      follows: (I) absolutely non-curative resection, (1) palliative tumor extirpation
      (palliative), (2) remaining tumor in (a) lymph nodes (Ly rem), (b) chest wall or
      diaphragm (Ch/Dia rem), or (c) bronchial stump (Bro rem), (3) intrapulmonary
      metastasis (PM), (4) pleural dissemination or pleuritis carcinomatosa (P1/Diss),
      (5) metastasis in other organs (Meta); (II) relatively non-curative resection,
      (1) incomplete resection of lymph nodes (R0-1), (2) group 2b or 3 lymph node
      metastasis (2b Ly). The 5-year actuarial survival rate of the Bro rem group was
      35.6%, being the best among the absolutely non-curative cases, followed by the PM
      group (33.7%), the Pl/Diss group (31.6%) and the Ch/Dia rem group (29.7%). The
      results of the Ly rem and Meta groups were poor at 5.4% and 0%, respectively.
      Those of the relatively non-curative group were 24.4% (R0-1 group) and 11.6% (2b
      Ly group). Non-curative resection is not the treatment of choice, but by
      analyzing the causes of non-curative resection, we may able to improve the
      prognosis of advanced cases of lung cancer.

PMID- 7812701
TI  - Pulmonary infections in lung cancer patients at diagnosis.
AB  - We carried out a prospective study involving 96 consecutive lung cancer patients
      at diagnosis, in order to determine through quantitative cultures of the
      bronchoalveolar lavage (BAL) fluid, the prevalence of pulmonary infections; we
      also evaluated the relationship between a patient's performance status,
      immunocompetence, lung cancer stage, histotype and the occurrence of respiratory
      infections. The patients (81 males, 15 females) had a mean age of 64 +/- 9 years.
      Of these, 62 were smokers, 30 were ex-smokers and four had never smoked. Sixty
      seven patients had a prior history of chronic bronchitis. A total of 42 micro
      organisms were cultured from the BAL fluids of 33 patients (34.3%). Fifty percent
      of these micro-organisms were gram-negative, 33.3% were gram-positive and the
      remaining 16.7% were other micro-organisms. The bacilli most often isolated were
      the Haemophilus species, accounting for 38.8% of all gram-negative bacilli. The
      most frequently isolated gram-positive pathogen was the Staphylococcus aureus. We
      have not found a significant relationship between the presence of a respiratory
      infection and the different cell types separately analyzed, nor with SCLC and
      NSCLC patient groups, nor with the stage of the disease. The performance status,
      the immunoregulatory ratio and the lymphocyte subsets were not significantly
      different in patients with or without a pulmonary infection. We think that the
      identification of a definite etiologic agent is of great importance for a
      rational anti-microbial treatment of pulmonary infections.

PMID- 7812702
TI  - High dose doxorubicin plus cisplatin in the treatment of unresectable
      mesotheliomas: report of four cases.
AB  - Only a very small proportion of all patients with mesotheliomas can be cured
      surgically. Both radiotherapy and standard chemotherapy are generally considered
      to be of only limited usefulness. In this paper, we report four patients with
      unresectable mesotheliomas treated with the combination of cisplatin 105-120
      mg/m2 plus doxorubicin 90 mg/m2. Toxicity was substantial, in that all four
      patients developed neutropenic sepsis and other grade 3 toxicity, but there were
      no treatment-related deaths. There were two patients with complete remissions
      (one persisting at > 4 years), one partial remission, and one stable disease with
      marked symptomatic improvement. This combination is toxic, but the anecdotal
      evidence of efficacy is suggestive that it may possibly be more active than lower
      doses of chemotherapy. It warrants further study in good performance status
      patients with unresectable mesotheliomas.

PMID- 7812703
TI  - Treatment-related deaths in small cell lung cancer trials: can patients at risk
      be identified? Medical Research Council Lung Cancer Working Party.
AB  - OBJECTIVES: This paper investigates the problem of treatment-related deaths in
      small cell lung cancer (SCLC). DESIGN: To observe and define increased hazard
      levels, and to identify factors relating to these excess deaths. SETTING: The
      United Kingdom. SUBJECTS: A total of 2196 patients entered into the series of six
      randomised clinical trials in SCLC conducted by the Medical Research Council
      (MRC) Lung Cancer Working Party (LCWP). RESULTS: In this large series of patients
      an increased risk of death in the second week after commencing the first cycle of
      chemotherapy was observed, suggesting that of the 10% of patients who died within
      3 weeks of starting chemotherapy, half may have been treatment-related. Much less
      additional risk was associated with subsequent cycles of chemotherapy, and no
      additional risk with either initial surgery or radiotherapy. Radford et al. [Eur
      J Cancer 1993; 29A: 81-86] suggested that the risk factors for death from sepsis
      were a Karnofsky Performance (KP) score of < or = 50 (translated as a WHO
      performance grade (PS) > or = 3), age > 50 years and three or more drugs in the
      chemotherapy regimen utilised. Starting with this model we found that our data
      suggest it can be refined by omitting age and including a white blood cell count
      > or = 10,000/mm3 (this variable was not tested by Radford), and changing the
      other categories to WHO PS > or = 2 (KP < or = 70), and four or more drugs.
      Within our data this revised model identified a high risk group of patients with
      an excess death rate of more than 15% in the second week after starting
      chemotherapy. Radford et als' suggestion that high risk patients be given half
      doses of drugs at the first cycle should be tested in a randomised clinical
      trial.

PMID- 7812704
TI  - Cisplatin-5-fluorouracil in small cell lung cancer. A phase II study in 109
      patients.
AB  - One hundred nine previously untreated patients with small cell lung cancer were
      treated for five consecutive days with 20 mg/m2/day of cisplatin and 600
      mg/m2/day of 5-fluorouracil. One cycle of chemotherapy was administered every
      three weeks. The patients received a median number of three cycles. Then they
      were transferred to CAE chemotherapy. A 77% overall response rate (95% confidence
      interval of 0.70-0.85) was observed after initial cisplatin-5FU treatment. Twenty
      three complete responses (21%) and 62 partial responses (56%) were obtained. In
      cerebral metastases the response rate was high at 91% (21 out of 23), with 43%
      complete responses. In the limited forms, statistical survival at 1 year was 25%.
      A Grade 3-4 thrombocytopaenia was observed in 10 patients (9%) and a Grade 2-3
      leukopaenia in four patients. Three patients suffered from a Grade 2 cardiac
      toxicity. The cisplatin-5-fluorouracil combination demonstrates promising initial
      response rate in small cell lung cancers. Its main interest is in its important
      action on cerebral metastases and its moderate haematological toxicity.

PMID- 7812705
TI  - Combination chemotherapy with cyclophosphamide, epirubicin and etoposide in small
      cell lung cancer.
AB  - From March 1987 to February 1991, 136 patients with untreated small cell lung
      cancer (64 patients with limited disease and 72 with extensive disease), were
      treated as part of a prospective multi-center study, with a combination of
      cyclophosphamide 1000 mg/m2 i.v. on day 1, epirubicin 70 mg/m2 i.v. on day 1 and
      etoposide 100 mg/m2 i.v. on days 1, 3 and 5. Courses were repeated every 3 weeks.
      One-hundred thirty-four patients were evaluable. There were 42 (31%) complete
      responses and 66 (49%) partial responses for an overall response rate of 80% (95%
      confidence interval 71-87%). A complete response was seen in 24 patients (38%)
      with limited disease and in 18 patients (26%) with extensive disease, while a
      partial response was observed for 31 (48%) and in 35 (50%) patients,
      respectively. The median duration of response for all patients was 8.9 months
      (range, 1-60+ months). The median duration of survival for the entire group was
      11.4 months (12.5 months for limited disease and 9.8 months for extensive
      disease). The 2-year survival rate for the whole group was 13%. The main side
      effects were myelosuppression, alopecia, nausea and vomiting. Grade 4 toxicity
      was seen in 8.5% of patients. In conclusion, the studied regimen was found to be
      active and well tolerated and may be considered as an alternative to standard
      chemotherapy combinations in SCLC.

PMID- 7812706
TI  - The results of surgical treatment of non-small cell lung cancer at the
      Pneumological Clinic in Prague, Czech Republic 1985-1990.
AB  - In the Czech Republic, lung cancer is the most frequent malignant tumor in men.
      In 1990 the incidence was 99.6/100,000 for men and 15.8/100,000 for women.
      Neither diagnostic nor therapeutic approaches have changed significantly in the
      last 10 years. Patients undergoing lung resection have a chance of long-term
      survival. In this retrospective study, the authors analysed the data of 252
      patients undergoing the operation for non-small cell lung cancer (NASCL) in the
      period 1985-1990. Of all patients who in that period had lung cancer diagnosed in
      our clinic, only 22% were operated on. Lobectomy was the most frequent type of
      operation (45%), and exploratory thoracotomy was carried out in 13%. The
      epidermoid type of cancer was the most frequent one (62%). Comparing cTNM with
      pTNM, concordant results were found in 55% of the series, 39% were clinically
      underestimated and 6% overestimated. By the time of the evaluation (31 December
      1992), 78% of all patients who had undergone surgery during the study period had
      died. The most frequent cause of death was lung cancer metastasis. In the
      subseries of patients who died within 1 month after surgery (10% of all
      patients), the most frequent cause of death was pneumonia. The survival curve
      shows the best prognosis for patients in the Ist TNM stage, with 40% surviving 5
      years. The authors consider the results of this study to favour aggressive
      surgical treatment of NSCLC patients.

PMID- 7812707
TI  - Combination chemotherapy with cisplatin-vinblastine in malignant mesothelioma.
AB  - From June 1985 to March 1993, 20 consecutive patients with histologically proven
      malignant mesothelioma were treated with cisplatin 100 mg/m2 i.v. infusion on day
      1 and vinblastine 6 mg/m2 i.v. on day 1 and 8. Treatment was repeated every 4
      weeks until progression. All patients were evaluated clinically and by CT-scan
      and were staged (Stage IV), according to Butchard's criteria, on entry to the
      study. None had prior surgical excision. Eighty-one chemotherapy cycles were
      administered to 20 patients. One complete response, four partial responses, nine
      stable diseases and six progressions were noted. One partial responder entered
      complete response following an operation. Toxicity was acceptable and no
      treatment-related deaths occurred. The median survival for responders was 19.3
      months; for patients with stable disease 15.7 months and for non-responders, 5.2
      months. The mean duration of response was 13 months. We conclude that for this
      small group of patients, the combination cisplatin-vinblastine is effective, with
      acceptable toxicity in malignant mesothelioma. Further study with a larger number
      of patients is necessary.

PMID- 7812708
TI  - Phase II trials of malignant mesothelioma: a commentary and update.

PMID- 7812709
TI  - Recent trends in the management of lung cancer. A summary of the 14th Annual
      Cancer Conference of the Kuwait Cancer Control Centre (KCCC).

PMID- 7812710
TI  - IASLC Conference. A summary of the 2nd Central European Conference on Lung
      Cancer. Ljubljana, Slovenia, 13-16 April 1994.

PMID- 7812711
TI  - The ABC of EF-G.
AB  - The recently solved crystal structures of Thermus thermophilus elongation factor
      G, with and without GDP, reveal a protein of five domains with surprising
      features which can be correlated with biochemical data to suggest probable
      functional roles.

PMID- 7812712
TI  - p53: a cellular Achilles' heel revealed.
AB  - Many human cancers result from the inactivation of p53, a protein central to DNA
      repair. Recent papers reporting the structures of two p53 domains help to
      rationalize the wealth of information about this protein.

PMID- 7812713
TI  - The ribonucleotide reductase jigsaw puzzle: a large piece falls into place.
AB  - The three-dimensional structure of ribonucleotide reductase protein R1 from
      Escherichia coli reveals a novel 10-stranded alpha/beta barrel fold. A long loop
      penetrates the center cavity to assemble the active site cysteine triad.

PMID- 7812714
TI  - The 2.8 A crystal structure of peroxisomal 3-ketoacyl-CoA thiolase of
      Saccharomyces cerevisiae: a five-layered alpha beta alpha beta alpha structure
      constructed from two core domains of identical topology.
AB  - BACKGROUND: The peroxisomal enzyme 3-ketoacyl-coenzyme A thiolase of the yeast
      Saccharomyces cerevisiae is a homodimer with 417 residues per subunit. It is
      synthesized in the cytosol and subsequently imported into the peroxisome where it
      catalyzes the last step of the beta-oxidation pathway. We have determined the
      structure of this thiolase in order to study the reaction mechanism, quaternary
      associations and intracellular targeting of thiolases generally, and to
      understand the structural basis of genetic disorders associated with human
      thiolases. RESULTS: Here we report the crystal structure of unliganded yeast
      thiolase refined at 2.8 A resolution. The enzyme comprises three domains; two
      compact core domains having the same fold and a loop domain. Each of the two core
      domains is folded into a mixed five-stranded beta-sheet covered on each side by
      helices and the two are assembled into a five-layered alpha beta alpha beta alpha
      structure. The central layer is formed by two helices, which point with their
      amino termini towards the active site. The loop domain, which is to some extent
      stabilized by interactions with the other subunit, runs over the surface of the
      two core domains, encircling the active site of its own subunit. CONCLUSIONS: The
      crystal structure of thiolase shows that the active site is a shallow pocket,
      shaped by highly conserved residues. Two conserved cysteines and a histidine at
      the floor of this pocket probably play key roles in the reaction mechanism. The
      two active sites are on the same face of the dimer, far from the amino and
      carboxyl termini of both subunits and the disordered amino-terminal import signal
      sequence.

PMID- 7812715
TI  - Crystal structure of the FAD-containing fragment of corn nitrate reductase at 2.5
      A resolution: relationship to other flavoprotein reductases.
AB  - BACKGROUND: In the biological assimilation of nitrate in plants and
      microorganisms, nitrate is reduced to ammonium by transfer of eight electrons in
      a two-step process. The first step of the pathway, the reduction of nitrate to
      nitrite, is catalyzed by nitrate reductase, a multi-redox cofactor enzyme which
      belongs to the class of flavoprotein pyridine nucleotide cytochrome reductases.
      The enzyme can be divided into three functional fragments that bind the cofactors
      molybdopterin, heme-iron and flavin adenine dinucleotide (FAD)/nicotinamide
      adenine dinucleotide (NADH). RESULTS: Here we describe the crystal structure of
      the recombinant cytochrome b reductase fragment of corn nitrate reductase, in
      complex with the cofactor FAD, determined to 2.5 A resolution. This catalytically
      competent fragment of nitrate reductase consists of two domains, the amino
      terminal lobe, which binds FAD, and the carboxy-terminal lobe, which presumably
      binds NADH, connected by a linker region. CONCLUSIONS: Nitrate reductase belongs
      to the class of flavoprotein pyridine nucleotide cytochrome reductases, a
      subgroup in the family of ferredoxin reductase-like flavoproteins. Comparison
      with other members of this family reveals that large structural differences are
      found in the relative orientation of the cofactor binding lobes. This indicates
      that conformational changes might be important for biological function.

PMID- 7812716
TI  - Visualization of fusion activation in the Semliki Forest virus spike.
AB  - BACKGROUND: Viral spike proteins such as those of Semliki Forest virus (SFV)
      undergo a conformational change triggered by low pH which results in the fusion
      of the viral envelope with cellular membranes. The viral spike precursor of SFV
      is insensitive to low pH, and hence is fusion incompetent, until it is
      proteolytically cleaved to give the fusion competent mature form. RESULTS: Three
      dimensional image reconstructions from cryo-electron micrographs were used to
      compare the virion structure of wild-type SFV with that of a mutant SFV in which
      cleavage of the spike precursor had been blocked. Upon maturation to the fusion
      competent form, the spike undergoes a conformational change in which copies of
      the polypeptide containing the fusion sequence (E1) move from peripheral to
      lateral positions bringing them closer together. CONCLUSIONS: This first
      visualization of the maturation of a viral spike protein complex suggests a
      mechanism for the conformational change which controls the fusion process.

PMID- 7812717
TI  - Use of a purified heterodimer to test negative cooperativity as the basis of
      substrate inactivation of Escherichia coli thymidylate synthase (Asn177-->Asp).
AB  - BACKGROUND: Thymidylate synthase (TS) converts deoxyuridylate to thymidylate, an
      essential DNA precursor. Replacement of Asn177 with aspartate (Asn177-->Asp) in
      Escherichia coli TS creates a novel ability to methylate 2'-deoxycytidylate
      (dCMP). The dCMP-methylase activity of TS(Asn177-->Asp) is transiently
      inactivated by reaction with deoxyuridylate and methylene-tetrahydrofolate, the
      methyl donor. We have tested the possibility that the inactivation is due to
      negative cooperativity, created in the TS dimer by the Asn177-->Asp mutation.
      RESULTS: A heterodimeric form of TS, containing one wild type and one Asn177-
      >Asp active site, was created to test for negative cooperativity. Substrate
      inactivation still occurred, even with the mutation present at only one active
      site. CONCLUSIONS: Inactivation of TS(Asn177-->Asp) by deoxyuridylate is not due
      to negative cooperativity created by the mutation. The 'artificial isozyme'
      method we have developed for purifying heterodimers away from the progenitor
      homodimers is generally applicable to other hetero-oligomeric proteins.

PMID- 7812718
TI  - High-resolution solution structures of oxidized and reduced Escherichia coli
      thioredoxin.
AB  - BACKGROUND: Thioredoxin participates in thiol-disulfide exchange reactions and
      both oxidized thioredoxin (disulfide form) and reduced thioredoxin (dithiol form)
      are found under physiological conditions. Previous structural studies suggested
      that the two forms were extremely similar, although significant functional and
      spectroscopic differences exist. We therefore undertook high-resolution solution
      structural studies of the two forms of Escherichia coli thioredoxin in order to
      detect subtle conformational differences. RESULTS: The solution structures of
      reduced and oxidized thioredoxin are extremely similar. Backbone structure is
      largely identical in the two forms, with slight differences in the region of the
      active site, which includes Cys32 and Cys35. The side chain sulfur atom of Cys32
      is tilted away from that of Cys35 in the reduced form of the protein to
      accommodate the increase in S-S distance that occurs upon reduction of the
      disulfide, but the chi 1 angles of the two cysteines remain the same in the two
      forms. CONCLUSIONS: Only subtle conformational changes occur upon changing the
      oxidation state of the active site cysteines, including the positions of some
      side chains and in hydrogen bonding patterns in the active site region.
      Functional differences between the two forms are probably therefore related to
      differences in local conformational flexibility in and near the active site loop.

PMID- 7812719
TI  - Transmembrane signalling and the aspartate receptor.
AB  - BACKGROUND: The aspartate receptor is a transmembrane protein that mediates
      bacterial chemotaxis. The structures of the periplasmic ligand-binding domain
      reveal a dimer, each subunit with four alpha-helix bundles, with aspartate
      binding to one of two sites at the subunit interface. The transmembrane regions
      of the receptor were not included in these structures. RESULTS: To investigate
      the structure of the transmembrane region, we have made a mutant protein with two
      cross-links, restraining the subunit-subunit interface on both sides of the
      membrane, and have made an energy-minimized model of the transmembrane region. We
      demonstrate that the transmembrane helices form a coiled coil which extends from
      the periplasmic subunit through the membrane. We have constructed a model of the
      ligand-binding domains with the amino-terminal transmembrane helices.
      CONCLUSIONS: We draw three conclusions from our model. Firstly, the interface
      between receptor subunits in the intact receptor consists of an uninterrupted
      coiled coil. Secondly, this structure rules out several postulated mechanisms of
      signalling. Thirdly, side chain packing constraints within the helices dictate
      that local structural changes must be small, but are propagated over a long
      distance rather than being dissipated locally. Low energy changes in the
      conformation of side chains are a probable mechanism of signal transduction in
      the aspartate receptor.

PMID- 7812720
TI  - F1-ATPase structure: getting our bearings for ATP synthesis.

PMID- 7812721
TI  - Dorothy Hodgkin 1910-1994.

PMID- 7812722
TI  - Backward bicoid?

PMID- 7812723
TI  - Triadic discrimination testing: refinement of Thurstonian and sequential
      sensitivity analysis approaches.
AB  - The effect of cognitive search strategies and variations in the oral environment
      on discrimination test performance were investigated. Subjects were required to
      discriminate between low concentration NaCl solutions and water using the 3-AFC
      and triangle test protocols. As predicted by Thurstonian modeling, subjects
      obtained a higher proportion of correct tests for the 3-AFC protocol than for the
      triangle protocol. The d' values obtained from both protocols corresponded. As
      predicted by the Sequential Sensitivity Analysis Model, which is largely based on
      changes in the oral environment, subjects obtained a higher proportion of correct
      tests for triads containing one NaCl stimulus than for triads containing one
      water stimulus. Measurement of physical signal strengths of the stimuli, by
      analysing the Na cation concentration change in the oral environment on tasting,
      indicated that the classical Thurstone-Ura two-distribution model was
      insufficient. The strong carry-over effects in the chemical senses require a
      model based on more than two distributions. It was also noted that subjects did
      not always use the search strategy required for a given test protocol. The
      artifactual effects of strategy change during an experiment are discussed.

PMID- 7812724
TI  - The significance of apical K+ channels in mudpuppy feeding behavior.
AB  - Behavioral experiments were conducted to determine the effects of known potassium
      channel blockers, minnow extract (a natural food substance), and other taste
      stimuli on feeding behavior in the mudpuppy (Necturus maculosus). Groups of 10-15
      mudpuppies were presented with one or more of the following chemicals dissolved
      in gelatin cubes: H2O (control), NaCl (1.0 M; 0.2 M), crude minnow extract (0.1
      g/ml), CaCl2 (1.0 M), citric acid (0.1 M; pH 2, 0.01 M; pH 3), quinine HCl (0.1
      M), tetraethylammonium chloride (TEA; 0.1 M), KCl (1.0 M) and an amino acid
      mixture containing L-phenylalanine, L-arginine, L-histidine, L-valine, L-glutamic
      acid and L-lysine at concentrations of 0.02 M and 0.04 M each. Crude minnow
      extract was centrifuged and separated into components consisting of the following
      fractions: > 500 D, > 1000 D and > 14,000 D, each of which was presented to
      mudpuppies in cubes. Results were expressed as the percentage of animals
      rejecting the cube within 5 min of taking the cube into the oral cavity.
      Statistical analysis using the Fisher exact test indicated that cubes containing
      chemicals known to block (CaCl2, TEA, citric acid and quinine) or permeate (KCl)
      apical K+ channels in mudpuppy taste cells were more aversive than control cubes,
      and aversion was concentration-dependent. In contrast, cubes containing minnow
      extract and components of minnow extract < 14,000 D were significantly preferred
      over control cubes. Cubes containing a mixture of minnow extract and an aversive
      chemical were significantly less aversive than cubes containing only an aversive
      chemical. These findings suggest that activation of the apical K+ conductance in
      mudpuppy taste cells triggers an aversive response, but the aversion can be
      ameliorated by low molecular weight compounds present in minnow extract.

PMID- 7812725
TI  - Capability of intensity discrimination in multiple receptor model of insect
      taste.
AB  - A simple model in which one CNS taste neuron integrates inputs from multiple
      peripheral receptors is introduced in order to investigate the mechanism of acute
      intensity taste discrimination in flies. Information theory is applied to
      evaluate the acute ability of discrimination provided by the model. The present
      analysis is carried out under two statistical conditions concerning the
      uncertainty of receptor response. Based on experimental data obtained by Smith et
      al. (1983), we estimate the mutual information entropy of the model. The
      numerical results obtained here indicate that the uncertainty observed in a
      single receptor response is dramatically reduced by the central integration.
      Furthermore, each of the eleven stimulus intensity levels experimentally applied
      by Smith et al., can be discriminated completely by integrating the responses of
      the realistic number of receptors (33-212). Such a great improvement of the
      differential sensitivity in the model resolves the discrepancy between the low
      differential sensitivity of single sugar receptors (Smith et al., 1983) and the
      high sensitivity obtained in the feeding behavior (Dethier and Rhoades, 1954;
      Dethier and Bowdan, 1984) of the blowfly.

PMID- 7812726
TI  - Perception of odor mixtures by the spiny lobster Panulirus argus.
AB  - We used spiny lobsters (Panulirus argus) in a discrimination learning procedure
      with aversive conditioning to examine their behavioral discrimination of
      adenosine-5'-monophosphate (AMP), betaine, L-cysteine and their binary mixtures.
      Our results show that spiny lobsters can clearly discriminate among binary
      mixtures and their components. Lobsters aversively conditioned to avoid
      responding to a binary mixture continued to respond to that mixture's components,
      and lobsters that were aversively conditioned to avoid responding to a compound
      tended to continue to respond to binary mixtures containing that compound. Thus,
      responses of conditioned lobsters to binary mixtures were not usually
      intermediate between the responses to the mixtures' components, which might be
      expected for response-matched compounds. This result might arise from any of
      several factors. First, it might result from mixture interactions in the
      peripheral olfactory system, if the responses of olfactory receptor neurons to
      one component of a binary mixture were suppressed by the other component, making
      the response to the mixture more similar to the suppressing component.
      Electrophysiological data from a population of 50 singly-recorded olfactory
      receptor neurons (Daniel and Derby, 1994) do not consistently support this idea.
      A second possible reason for the behavioral response to a binary mixture not
      being intermediate between the responses to its components involves higher order
      processing, such as mixture interactions generated in olfactory interneurons in
      the CNS (which is known to occur: Derby et al., 1985; Ache, 1989), configural
      learning or associative processing.

PMID- 7812727
TI  - The effect of the sweetness inhibitor 2(-4-methoxyphenoxy)propanoic acid (sodium
      salt) (Na-PMP) on the taste of bitter-sweet stimuli.
AB  - The effect of the sweetness inhibitor 2(-4-methoxyphenoxy)propanoic acid (sodium
      salt) (Na-PMP) on the taste and temporal properties of a range of bitter-sweet
      stimuli was determined using a trained sensory panel. Na-PMP was found to be an
      effective inhibitor of the sweetness response of all stimuli tested, reducing
      both sweetness intensity and persistence. The inhibitor was found to be specific
      to sweet taste, no reduction in bitterness intensity or persistence was observed
      at the concentrations of Na-PMP employed in this study. The results therefore do
      not support the claim of Fuller and Kurtz (1991), that Na-PMP is a potent
      bitterness inhibitor, but rather support the existence of two distinct receptor
      sites/loci in sweet and bitter chemoreception.

PMID- 7812729
TI  - Olfactory detection of a complex versus a simple substance in advanced age.
AB  - Thresholds for lavandin oil (highly complex substance) and n-butanol (single
      compound) averaged higher in subjects over 70 years than in controls under 30, by
      comparable amounts and with about the same variability.

PMID- 7812728
TI  - Functional imaging of effects of fragrances on the human brain after prolonged
      inhalation.
AB  - Beside olfactory or trigeminal stimulation of chemosensory receptor-cells some
      results in published literature suggest that fragrances show a direct affect on
      the brain. The effect of the fragrance 1,8-cineol, which was described in
      literature as 'stimulating', on regional and global cerebral blood flow (rCBF and
      gCBF) in the human brain after prolonged inhalation was investigated. The results
      show an increase of global-CBF without preference to primary or secondary
      olfactory centres after an inhalation-time of 20 min.

PMID- 7812730
TI  - Angiotensin receptors: relevance in development and disease states.

PMID- 7812731
TI  - The apical membrane water channel of collecting ducts.

PMID- 7812732
TI  - Hypertrophy of proximal tubular epithelial cells induced by low pH in vitro is
      independent of ammoniagenesis.
AB  - Metabolic acidosis can lead to tubular hypertrophy in vivo. This is thought to
      arise from stimulation of renal production of ammonia, a known hypertrophic
      agent. To examine this effect in vitro, confluent opossum (OK) proximal tubular
      epithelial cells were cultured at acidic pH (7.21 +/- 0.02) or at control pH
      (7.37 +/- 0.01) for 4 days. Protein content was 9% higher at acidic pH whereas
      DNA content was unaffected. The resulting increase in mean cell size (protein/DNA
      ratio) was 10% but correlated inversely with the mass of cells in control wells,
      varying from +48% at low cell mass to -14% at high cell mass. In contrast, low pH
      decreased 3H-thymidine incorporation by 9%. However, ammonia production was
      unaffected. These changes in protein/DNA ratio and 3H-thymidine incorporation
      cannot therefore be attributed to acid-induced ammoniagenesis and imply that low
      pH exerts a more direct effect on tubular cell growth than previously envisaged.

PMID- 7812733
TI  - Comparison of the renal effects of urodilatin and atrial natriuretic factor:
      effect of changes in sodium status.
AB  - Urodilatin is an amino terminally extended form of atrial natriuretic factor
      (ANF) which is resistant to enzymatic cleavage by renal neutral endopeptidase
      (NEP: EC 3.4.24.11). The renal effects of infusion into the renal artery of
      equimolar doses of urodilatin or ANF have been compared following changes in Na
      status in conscious sheep. In all conditions urodilatin was a more potent
      natriuretic stimulus than was ANF and the natriuretic response to urodilatin was
      modulated by sodium status in the same way as the response to ANF: diminished by
      sodium depletion and enhanced by sodium loading. This study does not support the
      hypothesis that changes in NEP activity contribute to the modulation of the
      natriuretic response to ANF which is observed with modification of sodium status.

PMID- 7812734
TI  - Further studies on the characterization of a renotropic activity detected in
      uninephrectomized rat plasma.
AB  - Using chromatographic techniques, we have purified a peptide responsible, at
      least in part, for the renotropic activity detected in 24-hour uninephrectomized
      adult rat plasma. The most purified material behaved as a single component when
      analyzed by reversed-phase HPLC. The purified factor stimulates DNA synthesis in
      isolated rat proximal tubules and proximal tubular cell (LLC-PK1) cultures. This
      effect was abolished by pretreatment with protease K, with an intracellular
      calcium chelator or with indomethacin. This factor was also mitogenic for rat
      mesangial cells. In contrast, neither Madin-Darby canine kidney cells nor rat
      liver cells responded to the growth factor. Using the same purification
      procedure, a bioactive factor with an amino acid composition almost identical to
      that of this renotropic peptide was isolated from sham-operated or normal rat
      plasma. However, only uninephrectomized plasma after gel filtration showed
      renotropic activity, which was inhibited by the corresponding chromatographic
      fraction from sham-operated plasma. Our findings suggest that a change in the
      concentration of a circulating inhibitor(s) appears to account for the
      differences in the activity of sham-operated or control plasma and
      uninephrectomized plasma on the growth of renal cells.

PMID- 7812735
TI  - Dopamine does not mediate protein-induced hyperfiltration.
AB  - Dopamine and a meat meal have both been used to stimulated hyperfiltration.
      Urinary dopamine has been said to rise after a meal. It has been suggested that
      the responses are the same. In order to clarify this relationship, the DOPA
      decarboxylase inhibitor carbidopa was used to abolish dopamine synthesis during a
      meat meal. Eight normal individuals were studied twice. On each occasion they ate
      a meat meal and resting and post-prandial haemodynamics were measured. On 1 of
      the 2 study days they received carbidopa which abolished renal dopamine
      synthesis. Despite this there was no change in resting haemodynamics and the meat
      meal response was preserved. We conclude that urinary dopamine does not rise
      after a meal and that dopamine does not mediate the meat meal response.

PMID- 7812736
TI  - Expression of the complement regulator factor C8 binding protein on human
      glomerular cells protects them from complement-mediated killing.
AB  - The complement-regulatory factor C8 binding protein (C8bp) was first identified
      on human erythrocyte membranes by its affinity for the complement component C8
      and its ability to inhibit lysis by homologous complement. Cultured human
      glomerular mesangial or epithelial cells (GEC) expressed C8bp on the cell surface
      and in the cytoplasm. Following stimulation of the glomerular cells with
      interleukin 1 beta, C5b-9 or with endotoxin, a transient, protein synthesis
      independent increase in C8bp surface expression was seen. Blocking of C8bp
      function with F(ab)2 fragment of an antibody to C8bp rendered GEC susceptible to
      complement-mediated killing, indicating that C8bp contributes to the cellular
      defense against complement attack.

PMID- 7812737
TI  - Induction of MHC class II molecules HLA-DR, -DP and -DQ and ICAM 1 in human
      podocytes by gamma-interferon.
AB  - MHC class II-encoded molecules HLA-DR, -DP and -DQ play a pivotal role in the
      human immune response. Their constitutive expression is restricted to a number of
      immunocompetent cells referred to as antigen-presenting cells. However, gamma
      interferon (gamma-IFN) has been shown to induce MHC class II molecule expression
      in several epithelia. Using flow cytometric analysis, we show here that normal
      and SV40-transformed human podocytes in culture constitutively expressed gamma
      IFN receptors. We also show that MHC class I molecules are constitutively
      expressed in these cells and that HLA-DR, -DP and -DQ expression, which is not
      found in unstimulated cells, can be induced by gamma-IFN stimulation. This
      induction was a time-dependent event, a lag phase of 24-48 h being necessary for
      MHC class II molecules to become detectable at the cell surface by flow
      cytometric analysis. Induction of MHC class II molecules in human podocytes also
      showed a concentration dependence, a plateau being reached at a concentration of
      500 IU of gamma-IFN/ml of culture medium. This effect was blunted by coincubation
      of the cells with an antihuman gamma-IFN receptor monoclonal antibody. HLA-DR
      expression was associated with specific mRNA accumulation, as detected by
      Northern blot analysis. By indirect immunofluorescence, the intercellular
      adhesion molecule 1 was also induced by gamma-IFN stimulation. Induction of DR,
      DP and DQ in human podocytes may be involved in the pathogenesis of immune
      glomerulonephritis in man.

PMID- 7812738
TI  - The effect of electric field gradient asymmetry on motionally averaged spin-1
      powder patterns.
AB  - The effect of an asymmetric electric field gradient tensor on anisotropic NMR
      spectra of spin-1 nuclei is investigated for fast molecular rotations and 2-site
      jump processes. When molecular rotations are fast, continuous, and complete, the
      peak-to-peak splitting of motionally averaged spin-1 NMR spectra can depend
      significantly on the inherent electric field gradient asymmetry, eta, for eta >
      or = 0.05. Parameters describing low-symmetry molecular motion which are
      extracted from fitting experimental data depend strongly upon eta. One
      implication of these phenomena is that even the modest electric field gradient
      asymmetry around deuterons in covalent bonds can contribute considerably to
      motionally averaged lineshapes, especially when molecular motions are not highly
      symmetric.

PMID- 7812739
TI  - 13C CP/MAS of LDLL mixtures of amino acids.
AB  - A unit cell in which three isomers are in an L configuration and one is in a D
      configuration is inherently asymmetrical. For LDLL mixtures of amino acids with
      identical chemical structures (apart from chirality), the inter- and
      intramolecular interactions observed from the 13C CP/MAS NMR spectra are even
      larger than those which have been observed with mixtures of diastereoisomers in
      the solid state. This occurs even though the chemical composition of these
      molecular clusters consists only of nearest neighbor enantiomers. Because D and L
      isomers have identical chemical shifts, changes in chemical shift and peak
      intensities of these asymmetrical solid mixtures cannot be unambiguously assigned
      to either the D or one of the L isomers. In LLDL mixtures of amino acids in which
      half is L isomers and the other half is DL isomers, the NMR spectra clearly
      depend upon which amino acid contains the D isomer. Any further structural
      interpretation of these molecular clusters is equivocal without assigning
      chemical shifts to the D isomer (or alternatively designated the R, [-] or [+]
      isomer). Both more rigorous mathematical analysis and new NMR experiments are
      required which link interactions at chiral centers with NMR spectra of LLDL
      mixtures in the solid state.

PMID- 7812740
TI  - 2H NMR lineshapes of immobilized uniaxially oriented membrane proteins.
AB  - As a method for the structure determination of integral membrane proteins or
      other large macromolecular complexes, a solid state 2H NMR approach is presented,
      capable of measuring the orientations of individual chemical bond vectors. In an
      immobilized uniaxially oriented sample, the bond angle of a deuterium-labelled
      methyl group relative to the axis of ordering can be calculated from the
      quadrupole splitting in the "zero-tilt" spectrum where the sample normal is
      aligned parallel to the spectrometer field direction. However, since positive and
      negative values of this splitting cannot be distinguished, there may appear to be
      two solutions, of which only one describes the correct molecular geometry. We
      show that it is possible to determine the bond angle uniquely between 0 degree
      and 90 degrees, by analysing the lineshapes of a tilt series of spectra acquired
      over different sample inclinations. The lineshape equation describing such
      oriented 2H NMR spectra will be derived (for asymmetry parameter eta = 0) and
      discussed, with an illustration of the various linebroadening effects from which
      the orientational distribution function in the macroscopically ordered system can
      be determined. This strategy is then applied to specifically deuterium-labelled
      retinal in dark-adapted bacteriorhodopsin, prepared in a uniaxially oriented
      sample from purple membrane fragments. From the quadrupole splitting in the zero
      tilt spectrum and by lineshape simulations, the deuteromethyl group at C20 on
      retinal is found to make an angle of 32 degrees +/- 1 degree with the membrane
      normal, and the sample mosaic spread to be around +/- 8 degrees. The resulting
      orientation of retinal is in excellent agreement with its known structure in
      bacteriorhodopsin, and together with the results on other methyl groups it will
      be possible to construct a detailed picture of the chromophore in the protein
      binding pocket.

PMID- 7812741
TI  - 71Ga and 31P MAS NMR spectroscopic studies of cloverite.
AB  - 71Ga and 31P MAS NMR studies have been undertaken of the gallophosphate molecular
      sieve, cloverite. Two 71Ga resonances were observed of the as-synthesized
      cloverite (ambient humidity) at 92 and -24 ppm. The first of these is assigned to
      five coordinate and the second to six coordinate gallium, where in both cases
      there is one fluoride ion in the first gallium coordination sphere. Dehydration
      of the sample decreased the intensity of the six coordinate signal relative to
      that of the five coordinate one, whereas hydrating had the reverse effect,
      suggesting that the upfield signal is due to six coordinate gallium sites
      generated through the adsorption of water. The 31P MAS NMR spectrum of a
      dehydrated sample revealed one weak resonance at -0.8 ppm as well as strong
      signals at -9.7 and -11.2 ppm. The -0.8 ppm resonance is attributed to the T5
      [P(OGa)3OH] sites whereas the strong signals are assigned to the T1-T4 sites
      [P(OGa)4]. Upon humidifying, several new resonances appear between 0 and -6 ppm
      which have been assigned to phosphorus atoms having nearest neighbour gallium
      atoms in varying degrees of hydration.

PMID- 7812742
TI  - Solid-state distortions of linear mono-, bi-, and trimetallic bis(tri-n
      butylphosphine) nickel and palladium complexes having 1,4-tetrafluorophenylene
      bridges as observed via 31P CP/MAS NMR spectroscopy.
AB  - 31P CP/MAS NMR spectra were recorded for a series of eight linear mono-, bi-, and
      trimetallic bis(tri-n-butylphosphine) nickel and palladium complexes having 1,4
      tetrafluorophenylene bridges. A2 type spectra were obtained with Ni(PBu3)2(1,4
      C6F4H)2 (I), Pd(PBu3)2(1,4-C6F2) (V) and [Pd(PBu3)2(1,4-C6F4H)]2(1,4-C6F4) (VII).
      AB type spectra were obtained with Ni(PBu3)2(1,4-C6F4H)Br (II), [Ni(PBu3)2(1,4
      C6F4)Br2 (III) and [Pd(PBu3)2Cl]2(1,4-C6F4) (VI). The 2JPP scalar coupling
      constants fell in the region of 300 to 450 Hz as expected for P-metal-P pairs in
      a trans configuration. The spectra of [Ni(PBu3)2]3(1,4-C6F4)2Br2 (IV) and
      [Pd(PBu3)2]3(1,4-C6F4)2Cl2 (VIII) consisted of overlapping A2 and AB spins
      systems. Large upfield and downfield shifts were measured in the solid samples
      relative to the corresponding 31P NMR spectra in CDCl3 solution. Correlating the
      31P CP/MAS NMR data with reported X-ray crystallographic measurements revealed
      that both the chemical inequivalence and the solid versus solution resonance
      frequency shifts were the result of ring current effects brought about by
      distortions from square-planar geometry at the metal centre in the solid state.

PMID- 7812743
TI  - Molecular dynamics in polycrystalline testosterone studied by proton NMR.
AB  - Polycrystalline testosterone (17 beta-hydroxy-4-androsten-3-one, C19H28O2) has
      been investigated by proton NMR methods between 70 K and the melting point 428 K.
      Reductions in dipolar second moment and two well-resolved minima in the spin
      lattice relaxation time measured at 25 MHz are ascribed to reorientation of the
      two methyl groups in the molecule. Activation energies Ea characterizing the
      motions were 6.1 +/- 0.5 and 11.9 +/- 0.9 kJ/mol; the pre-exponential time
      factors tau 0 were (2.3 +/- 0.1) x 10(-13) and (2.85 +/- 0.2) x 10(-13) s,
      respectively.

PMID- 7812744
TI  - Bi-exponential nuclear spin-lattice relaxation in solid hexafluoroacetylacetone.
AB  - The reorientation of CF3 rotors in solid hexafluoroacetylacetone has been studied
      using pulsed NMR techniques. The temperature dependence of both fluorine (19F)
      and hydrogen (1H) nuclear spin-lattice relaxation has been measured using
      saturation-recovery pulse sequences. Following saturation of one of the spin
      reservoirs, the evolution with time of the longitudinal magnetisations associated
      with both nuclei are observed to be strongly bi-exponential. A theory is
      presented for the spin-lattice relaxation which is mediated by the heteronuclear
      dipole-dipole interaction between 19F and 1H nuclei. The experimental results are
      in good quantitative agreement with this relaxation theory. The spectral density
      functions have been evaluated using the known molecular structure and they are
      consistent with the experimental data. From this analysis we conclude that the
      relaxation is dominated by an intramolecular 19F-1H dipolar interaction. The
      spectral density function J(0)(omega H-omega F) makes an important contribution
      to the relaxation theory with the result that the motional spectrum is
      conveniently sampled at the difference frequency between 1H and 19F Larmor
      precessions. Two physically distinguishable CF3 rotors have been identified in
      this investigation, their dynamics are characterised by activation energies of
      7.5 +/- 0.4 and 13.3 +/- 0.8 kJ mol-1, respectively.

PMID- 7812745
TI  - Determination of distributions of the quadrupole interaction in amorphous solids
      by 27Al satellite transition spectroscopy.
AB  - 27Al Satellite transition spectroscopy (SATRAS) has been used to extract both the
      quadrupole interaction and its distribution width from MAS spectra of glasses.
      Using this method a measurement at a single magnetic field strength allows one to
      obtain the true chemical shifts and the quadrupole interaction (and its
      distributions) with high accuracy, including quantification of the results. In
      contrast to earlier investigations the central transition MAS lineshapes can be
      described without assumptions and give correct relative proportions of
      differently coordinated Al species in glasses. The distribution model for the
      quadrupole interaction and the resulting MAS lineshapes are discussed in detail
      including a description of the experimental requirements. Experimental results of
      27Al SATRAS spectra of a ternary Al2O3-B2O3-P2O5 glass exhibiting 4-, 5-, and 6
      coordinated aluminum species clearly prove different mean values and distribution
      widths for the quadrupole interaction in the various AlOx polyhedra.

PMID- 7812746
TI  - High-resolution solid-state NMR for spin 3/2 and 9/2: the multi-quantum
      transitions method.
AB  - A new method of high-resolution NMR for spin 3/2 and 9/2 in the solid-state is
      proposed: the multi-quantum transitions technique. This method uses MAS (or VAS)
      in commercially available probeheads. For spin I = 3/2 the observation at 3v0 of
      samples rotating at 70.12 degrees completely eliminates 1st and 2nd order
      quadrupolar interactions and scales the shielding anisotropy by a factor of 0.98.
      For spin I = 9/2, lines observed at 7v0 in the MAS condition are clearly narrower
      and more separated than the corresponding ones observed at v0.

PMID- 7812747
TI  - Two-dimensional J-resolved 13C solid-state NMR analysis of the products of
      ethylene conversion on zeolite H-ZSM-5.
AB  - Two-dimensional (2D) J-resolved 13C NMR spectroscopy has been used to analyze the
      products of ethylene conversion inside the channels of zeolite H-ZSM-5 at 373 K.
      The observed 13C signals of aliphatic hydrocarbon fragments have been attributed
      to various CHn (n = 1-3) groups. Multiplicities and positions of these signals
      suggest that a mixture of branched and linear ethylene oligomers is formed inside
      zeolite H-ZSM-5.

PMID- 7812748
TI  - Spinning sidebands from chemical shift anisotropy in 13C MAS imaging.
AB  - Solid state imaging by 13C MAS imaging is described. The spinning sidebands
      occurring at moderate spinning speeds, which disturb the images, can be
      suppressed by TOSS. For rigid solids the spatial resolution that can be achieved
      in this way is better than that of 1H images at the same spinning speed.
      Spatially resolved spectra with or without spinning sidebands can likewise be
      recorded providing information about the isotropic and the anisotropic chemical
      shifts which can be exploited for the study of structure, order and dynamics. The
      techniques are demonstrated on a phantom made with 13C-labelled glycine.

PMID- 7812749
TI  - Characterization of sodium cations in dehydrated faujasites and zeolite EMT by
      23Na DOR, 2D nutation, and MAS NMR.
AB  - Sodium cations localized at crystallographically distinct cation sites in
      dehydrated zeolites were characterized using 23Na double rotation, two
      dimensional nutation, and magic-angle-spinning nuclear magnetic resonance
      spectroscopy. The new DOR NMR technique has been applied at different magnetic
      field strengths to determine the quadrupole parameters of the overlapping
      quadrupole patterns. In the NMR spectra of dehydrated NaY and NaEMT two signals
      of sodium cations were identified, a low-field gaussian line at -12 +/- 1 ppm and
      a high-field quadrupole pattern, with an isotropic chemical shift of -8 +/- 1 ppm
      and a quadrupole coupling constant of about 4 MHz. By comparison of the 23Na MAS
      NMR intensities of these signals with the population of the cation sites
      determined by XRD and by calculation of the electric field gradients, the former
      signal was attributed to sodium cations at the sites SI and the latter one to
      sodium cations at the sites SI' as well as SII in faujasite and zeolite EMT. This
      assignment has further been confirmed by 23Na MAS NMR studies of dehydrated HNaY
      and BaNaY zeolites.

PMID- 7812750
TI  - Solid-state NMR study of ultrastable zeolite Y modified with orthophosphoric
      acid.
AB  - 29Si, 27Al and 31P solid-state NMR under magic-angle spinning was used for the
      study of ultrastable zeolite Y modified with H3PO4. The material is a potential
      candidate for a new generation of oil-cracking catalysts. Bloch decay and cross
      polarization spectra were compared. It was found that amorphous aluminium
      phosphate is formed during the P-impregnation and the following activation, and
      that it occupies the zeolite surface and internal voids. For a high P-content
      under steaming conditions, aluminium phosphate is converted into a crystalline
      form. No evidence has been found for incorporation of P atoms into the zeolite
      framework.

PMID- 7812751
TI  - Experimental detection of multiple-quantum coherence transfer in coupled spin
      solids by multi-dimensional NMR experiments.
AB  - Three-dimensional multiple-quantum coherence experiments in coupled 1/2 spin
      solids have been designed to directly detect coherence transfers among all the
      accessible coherence orders during irradiation. The experiments have been
      performed on the coupled four-spin polycrystalline sample 1,2,3,4
      tetrachloronaphthalene-bis(hexachlorocyclopentadiene) adduct. The experimental
      results reveal how the coherences transfer in this spin system, which support the
      theoretically deduced selection rules and can be used to assist more precise
      description of multiple-quantum coherence dynamics.

PMID- 7812752
TI  - Sideband suppression in magic-angle-spinning NMR by a sequence of 5 pi pulses.
AB  - We report a symmetrical sequence of 5 pi pulses for total sideband suppression in
      magic-angle-spinning NMR. The sequence is almost evenly spaced and shorter than
      previous 4 and 6 pi pulse methods.

PMID- 7812753
TI  - Solid-state NMR studies of 1H spin diffusion in adsorbed organic molecules.
AB  - 1H spin diffusion times of toluene (MB) and tetrahydrofuran (THF) adsorbed on a
      series of porous solids (charcoal, SiO2 and Al2O3) were measured by a selective
      inversion technique. The experimental results show that they cover a wide range
      (from less than one millisecond to several hundreds of milliseconds). For all
      samples, a tri-exponential behavior was observed in the magnetization recovery
      processes of the negative peaks. This is attributed to the existence of the two
      different kinds of spin diffusion processes in addition to the T1 relaxation. One
      is assigned to the intermolecular spin diffusion between the surface acidic
      protons of the adsorbent and the organic molecules adsorbed on the solid surface,
      the other to the intramolecular spin diffusion of adsorbed molecules. Due to
      hydrogen bonding between the surface hydroxyl groups and the adsorbate, the
      intermolecular spin diffusion of THF adsorbed on various solids is more effective
      compared to that of adsorbed MB. In addition, the intermolecular 1H spin
      diffusion between charcoal and adsorbed THF molecules was confirmed by indirect
      measurement suggested by Tekely et al.

PMID- 7812754
TI  - Concentration and temperature dependence of diluent dynamics studied by line
      shape experiments on a phosphate ester in polycarbonate.
AB  - 31P Hahn spin echo line shape and proton line shape experiments are reported on
      bisphenol A polycarbonate (BPAPC)-tris(2-ethylehexyl)phosphate (TOP) systems to
      study the concentration and temperature dependence of the local dynamics. In an
      earlier 31P line shape study a lattice model was presented as a framework to
      interpret the plasticization and antiplasticization behavior of the diluent based
      on a fractional population given by the type of nearest neighbor contacts in the
      mixed polymer-diluent glass. In this study, 31P spin echo line shapes of BPAPC,
      with 5%, 10% and 15% TOP, which monitor the diluent dynamics, at different
      temperatures and echo delay times are simulated in terms of fast- and slow-moving
      components, and the resulting fractional populations are compared with that
      predicted by the lattice model. Comparisons with the lattice model calculations
      are also made in the simulation of the 1H line shapes on BPAPC with 5% and 10%
      TOP, which probes both the polymer and diluent dynamics, and on BPAPC with 5% and
      10% perdeuterated trioctylphosphate (DTOP), which detects only the polymer
      motion. Fairly good line shape simulations and agreement between the lattice
      model and the fitting results at low diluent concentrations are obtained in all
      cases. Restricted cone motion best describes the slow-moving component in the 31P
      line shape fittings. For the fast component, rotational Brownian diffusion with a
      distribution of correlation times corresponding to a stretched exponential
      function is used. An activation energy Ea of 56 kJ/mol and an exponent alpha of
      0.7 for the fractional exponential correlation function are obtained and used to
      calculate the mechanical loss peak which was compared with the experimental loss
      data. The plateau character of the fractional population as a function of
      temperature can also be interpreted and understood in terms of the lattice model.

PMID- 7812755
TI  - Spin density description of rotational-echo double-resonance, transferred-echo
      double-resonance and two-dimensional transferred-echo double-resonance solid
      state nuclear magnetic resonance.
AB  - The spin density matrix formalism has been applied to rotational-echo double
      resonance (REDOR), transferred-echo double-resonance (TEDOR) and two-dimensional
      (2D) TEDOR experiments in order to obtain an expression for the signal
      intensities. TEDOR spectra of 15N-labeled glycine were measured with different
      dipolar evolution times. 2D-TEDOR spectra were measured of doubly labeled glycine
      2-13C, 15N and of 15N-labeled glycine. Both the TEDOR and the 2D-TEDOR spectra
      were readily obtained although the 2D-TEDOR experiment on 15N-labeled glycine
      used a lot of machine time. Even though the 15N-1-13C dipolar coupling is
      relatively small (200 Hz), the 1-C resonance can still be observed.

PMID- 7812756
TI  - Adsorption of Na+ onto gamma-alumina studied by solid-state 23Na and 27Al nuclear
      magnetic resonance spectroscopy.
AB  - The adsorption of Na+ on gamma-alumina surfaces at four coverages of Na2CO3[5,
      10, 15 and 20% w/w)] was characterized by solid-state 23Na and 27Al nuclear
      magnetic resonance (NMR) spectroscopy. The experimental results suggest that two
      distinct adsorbed species are present on the alumina surface: surface species and
      surface salts. At the lower coverages of Na2CO3 (5 and 10%), the surface species
      is predominant, in which the Na+ cations are associated with the oxygen atoms of
      gamma-alumina. Increasing the loading level to 15% results in the appearance of a
      second adsorbed species that is attributed to the surface salt, Na2CO3, deposited
      on the solid surface. Further adsorption of Na2CO3 leads to an increase in the
      amount of surface salt while the amount of surface species remains unchanged. 1H
      27Al Cross-polarization magic angle spinning (CP-MAS) experiments give the
      evidence that some Na+ cations in the form of surface species are coordinated
      with the Bronsted acid sites of gamma-alumina. This may be the main driving force
      that improves appreciably the catalytic efficiency of an Na2CO3-Al2O3 catalyst.

PMID- 7812757
TI  - Quadrupole effects of spin-3/2 nuclei on the solid-state magic-angle spinning
      nuclear magnetic resonance spectra of spin-1/2 nuclei. Deviations from first
      order theory and implications concerning the sign of the indirect coupling
      constant.
AB  - The effect of the interaction between spin-3/2 and spin-1/2 nuclei on solid-state
      magic-angle spinning nuclear magnetic resonance (MAS NMR) spectra of the latter
      is studied in cases where deviations from first-order theory are expected. A
      comparison is made between the exact and first-order perturbation approaches.
      Both dipolar and indirect (iso- and anisotropic) coupling interactions are
      considered. Implications regarding 13C,35,37Cl, 31P,63,65Cu and 119Sn,35,37Cl
      cases are discussed. It is shown that in the latter two cases the sign of the
      indirect coupling constant J can be derived.

PMID- 7812758
TI  - 35Cl nuclear quadrupole resonance studies of molecular motions of ClO3- and water
      diffusion in Ca(ClO3)2.2H2O.
AB  - A 35Cl nuclear quadrupole resonance (35Cl-NQR) investigation of polycrystalline
      Ca(ClO3)2.2H2O is described. The 35Cl-NQR frequencies (vQ) for two resonance
      lines (vQ1 and vQ2), the spin lattice relaxation time (T1Q) for vQ2 only and the
      line width delta vQ2 were measured in the temperature range 292-345 K, except for
      the frequency measured up to 455 K. The observed decrease in the resonance
      frequencies with increasing temperature permitted the determination of the
      frequencies of librations of the ClO3- ion about two axes perpendicular to the
      three-fold axis of the ion mainly responsible for this effect. The temperature
      dependence of the relaxation time T1Q proved the occurrence of water diffusion
      and hindered rotation of ClO3- ions. The activation energies of these two
      molecular motions were determined, and their effect on the electric field
      gradient at the site of a chlorine nucleus was discussed. Temperature
      measurements of the line width delta vQ2 confirmed the conclusions drawn from the
      analysis of T1Q(T).

PMID- 7812759
TI  - Double-resonance circuit for nuclear magnetic resonance spectroscopy.
AB  - A new double-resonance probe circuit design is described. The circuit contains no
      quarter-wavelength elements or equivalents, yet nonetheless achieves adequate
      isolation between the two input channels. It contains relatively few components,
      and so is both compact and efficient. It has been incorporated in two solid-state
      nuclear magnetic resonance (NMR) probes, with excellent results.

PMID- 7812760
TI  - The cat pudendal nerve: afferent fibers responding to mechanical stimulation of
      the perineal skin, the vagina or the uterine cervix.
AB  - Some afferent fibers from the pudendal nerve of the female cat were stimulated by
      pressing on the perineal skin, the vagina or the uterine cervix. Three different
      types of skin mechanoreceptors were found: (1) with low threshold (< 20 mg) and
      slow-adapting discharges; (2) with high threshold (0.1-0.5 g) and slow-adapting
      discharges; and (3) with low threshold and fast-adapting discharges. Most of
      these receptors increased their firing frequency as the velocity of skin
      indentation was increased (velocity detectors). The average conduction velocity
      of the skin afferents was 29 +/- 9 m/s. The receptors located at the vagina
      showed a fast-adapting response to probing and were sensitive to the velocity of
      the probe movement. Most of these receptors, however, showed a slow adaptation
      when the vaginal wall was distended with a balloon. The conduction velocity in
      vaginal afferents was 37 +/- 16 m/s. Those receptors responding to pressure on
      the uterine cervix adapted slowly to constant pressure but were sensitive to the
      velocity of the pressure pulses. The conduction velocity in the afferents from
      the uterine cervix was 31 +/- 9 m/s.

PMID- 7812761
TI  - Swelling-induced K+ influx in cultured primary astrocytes.
AB  - The effect of swelling of cultured primary astrocytes from rat brain in hypotonic
      medium on K+ influx has been studied. A decrease in osmolality from 310 to 180
      mOsm increased the activity of sodium pump (ouabain-inhibited 86Rb+ influx) and
      Na+,K+,2Cl- cotransport (ouabain-insensitive bumetanide-inhibited 86Rb+ influx)
      by 70 and 35%, respectively. It is suggested that activation of these transport
      systems makes it possible to retain a high potassium concentration in the cells
      under regulatory volume decrease.

PMID- 7812762
TI  - Alterations of local cerebral glucose utilization in lean and obese fa/fa rats
      after acute adrenalectomy.
AB  - An animal model often used to investigate the aetiology of obesity is the
      genetically obese fa/fa rat. It has many abnormalities, including hyperphagia,
      hyper-insulinemia, insulin resistance, low cerebral glucose utilization and an
      overactive hypothalamo-pituitary adrenal (HPA) axis with resulting
      hypercorticism. Due to the latter consideration, the aim of this work was to
      study the impact of acute adrenalectomy (ADX) on the local cerebral glucose
      utilization (LCGU) of lean and obese fa/fa rats. ADX resulted in discrete
      increases in LCGU of regions common to both lean and obese rats. These common
      regions were found to belong to be related to the limbic system. Within this
      system, the LCGU of the brain of obese rats was either normalized to lean sham
      operated values or increased by ADX to a similar degree in both groups on a
      percentage basis. It was concluded that the LCGU of both lean and obese animals
      appears to be negatively regulated, albeit to different extents, by
      glucocorticoids. Such negative regulation is particularly salient within the
      limbic system of the lean rat and even more so in the fa/fa rat. It is suggested
      that the long-term hypercorticism of obese fa/fa rats due to abnormal regulation
      of the HPA axis may result in a decreased LCGU in limbic and related regions of
      the brain of fa/fa rats and contribute to the expression of the obese phenotype.

PMID- 7812763
TI  - NGF suppression of weight gain in adult female rats correlates with decreased
      hypothalamic cholecystokinin levels.
AB  - Effects of chronic intraventricular administration of nerve growth factor (NGF, 1
      microgram qod for 21 days) on weight gain, hypothalamic neuropeptide levels and
      choline acetyltransferase (ChAT) activity were determined in adult female Wistar
      rats. Rats chronically treated with cytochrome c (cc) gained 163 g over the 21
      day treatment schedule, whereas NGF-treated rats only gained 110 g. Thus, NGF
      treated rats gained 53 g less; this change in weight gain is equivalent to
      approximately a 20% decrease of total weight gain compared to the cc-treated
      control rats. Chronic NGF treatment significantly decreased hypothalamic
      cholecystokinin (CCK) levels by 24% (P = 0.0070), but did not alter either
      hypothalamic neuropeptide Y (NPY) or bombesin (BOMB) levels (98% and 105% of cc
      treated control levels, respectively). In addition, chronic NGF treatment did not
      significantly alter hypothalamic ChAT activity (95% of cc-treated control rats).
      The results of the present study suggest that NGF-induced decreases in weight
      gain are not the result of alterations of hypothalamic cholinergic function.
      However, it is possible that NGF-induced alterations of hypothalamic CCK
      synthesis and release may be involved in the NGF-induced decrease in weight gain.

PMID- 7812764
TI  - Structural studies of condensation products of biogenic amines as inhibitors of
      tryptophan hydroxylase.
AB  - The effects of condensation products of dopamine and indoleamines on the activity
      of tryptophan hydroxylase (TPH) were evaluated to determine the structures
      associated with modulation of this enzyme activity. The compounds having a
      catechol structure, such as 1-methyl-6,7-dihydroxy-1,2,3,4
      tetrahydroisoquinoline, markedly inhibited the activity of the enzyme prepared
      from the rat brain. The inhibition was non-competitive in terms of both the
      biopterin cofactor and the substrate L-tryptophan. Substitution on the one or two
      positions of catechol isoquinolines did not affect the inhibitory activity
      towards TPH. Among these compounds, a charged substance, 1,2[N]-dimethyl-6,7
      dihydroxy-isoquinolinium ion, was an extremely potent inhibitor; the Ki values
      were 0.88 +/- 0.17 and 0.64 +/- 0.08 microM (mean +/- S.D.) in terms of the
      substrate and cofactor, respectively. By contrast, the condensation products of
      tryptophan and tryptamine with acetaldehyde scarcely affected TPH activities. 1
      Methyl-1,2,3,4-tetrahydroisoquinoline, 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridinium ion (MPP+) were almost
      inactive. These results indicated that the catechol structure recognized and
      combined with TPH at a binding site different from that of the substrate or
      cofactor and the positive charge on the dopamine-derived substance enhanced the
      affinity to TPH. The selective inhibition of TPH by dopamine-derived catechol
      isoquinolines was discussed in relationship to the interactions between
      catecholamines, indoleamines and their metabolites in the brain under
      physiological and pathological conditions.

PMID- 7812765
TI  - GLUT2 expression in the rat retina: localization at the apical ends of Muller
      cells.
AB  - In order to understand the molecular basis of glucose regulation supporting
      visual function, this study examined the presence of GLUT2, a facilitated
      diffusion glucose transporter isoform, and delineated its localization in the rat
      retina. Reverse transcriptase-polymerase chain reaction (RT-PCR) demonstrated the
      presence of GLUT2 mRNA, and immunoblot analysis using polyclonal antibody
      specific to rat GLUT2 revealed a band at a molecular weight of approximately 60
      kDa, indicating the presence of GLUT2 protein in the rat retina. Fluorescence and
      electron microscopy localized GLUT2 expression to the apical ends of Muller cells
      that face the inter-photoreceptor space. These findings suggest that GLUT2 on
      Muller cells may control intra-retinal glucose homeostasis by performing both
      anterior and posterior glucose transport within the rat retina. This is the first
      study to provide evidence that GLUT2 is present in the mammalian central nervous
      system and indicates that GLUT2 may have local glucose homeostatic functions
      within the retina in addition to its role in the regulation of systemic blood
      glucose level.

PMID- 7812766
TI  - High expression of noradrenaline, choline acetyltransferase and glial fibrillary
      acidic protein in the epileptic focus consecutive to GABA withdrawal. An
      immunocytochemical study.
AB  - Interruption of a chronic GABA infusion into the rat somatosensory cortex induces
      the appearance of focal epileptic manifestations, known as the 'GABA withdrawal
      syndrome' (GWS). The aim of the present study was to determine, by
      immunocytochemistry, if neurotransmitters other than GABA are involved in GWS,
      namely: noradrenaline (NA), serotonin, choline acetyltransferase (CAT),
      cholecystokinin, neuropeptide Y, somatostatin and glial fibrillary acid protein
      (GFAP). Immunocytochemical data were compared in three animal groups: GABA-,
      saline- and L-aspartate (L-Asp)-infused rats. Only GABA-infused rats presented
      epileptic manifestations after interruption of the infusion. Saline- and L-Asp
      infused rats served as controls. Observations were limited to the region
      surrounding the cortical infusion site. GABA-infused rats showed in the zone of
      the epileptic focus a number of cell bodies strongly immunoreactive to NA
      antibodies much larger than control rats. In addition, NA-immunoreactive fibers
      formed a dense plexus and some of them were observed around perikarya. In saline-
      and L-Asp-infused rats, the NA-immunolabelled fibers were sparse and NA
      immunolabelling was rarely observed in cell bodies. These results contrast to
      those obtained for the serotonergic system, where no significant difference was
      observed among the three groups of rats. CAT immunolabelling was observed in cell
      bodies, but not in nerve terminals in rats of the three groups. The number of CAT
      immunoreactive cell bodies was much greater in GABA-infused rats than in the
      control animals. GFAP immunolabelling showed an important number of astrocytes
      throughout the cortex of the GABA-infused hemisphere, whereas, astrocytic
      reaction was limited to the infusion site in controls. Immunocytochemical data
      concerning peptides revealed cortical neuronal elements labelled similarly in the
      three groups of rats. Noradrenergic, cholinergic and glial modifications observed
      mainly in GABA-infused rats can result from lesion and from a specific action of
      GABA in chronic infusion. These modifications may contribute to the
      epileptogenesis of GWS, as recently demonstrated by electrophysiological
      recordings that show a modulating action of NA on firing activity of neurons
      involved in the epileptic focus.

PMID- 7812767
TI  - Inhibitor of antagonist binding to the muscarinic receptor is elevated in
      Alzheimer's brain.
AB  - The 100,000 x g supernatant fraction of human brain contains endogenous
      inhibitors of antagonist binding to the muscarinic receptor. Significantly
      greater inhibition was observed with Alzheimer's than non-demented control
      supernatant fractions. Low molecular weight inhibitor was separated from larger
      inhibitor species by membrane dialysis (3,500 dalton cut-off). The activity of
      low molecular weight inhibitor was greatly increased by sulfhydryl reducing
      agents. While the low molecular weight inhibitor was stable to heat, acid and
      base for short time periods (< 20 min), it was inactivated by acid hydrolysis
      (50% loss after 16 h, 100% loss after 96 h). The low molecular weight inhibitor
      activity is elevated approximately three-fold in Alzheimer's brain. The low
      molecular weight inhibitor from Alzheimer's brain was found to be a non
      competitive inhibitor. This is the first report of endogenous inhibitors in human
      brain of ligand binding to the muscarinic receptor and of increased inhibitor
      activity in Alzheimer's disease.

PMID- 7812768
TI  - alpha-Bungarotoxin blocks the nicotinic receptor mediated increase in cell number
      in a neuroendocrine cell line.
AB  - Exposure of H69 small cell lung carcinoma cells to nicotinic agonists resulted in
      a significant increase (up to 100%) in cell number after 6 to 12 days. The effect
      of nicotine (10(-8) M to 10(-4) M) was both dose and time dependent as was that
      of another nicotinic agonist cytisine (10(-6) M to 10(-4) M). Interestingly, both
      the nicotine and cytisine induced increases in H69 cell number were blocked by
      alpha-bungarotoxin, as well as d-tubocurarine a nicotinic blocker which appears
      to interact with most nicotinic receptors. These results suggest that the
      nicotine induced increase in cell number is mediated through an interaction at
      the nicotinic alpha-bungarotoxin receptor. This idea is further supported by
      experiments which show (1) that H69 cells possess high affinity alpha
      bungarotoxin sites (Kd = 25 nM, Bmax = 10.4 fmol/10(6) cells) with the
      characteristics of a nicotinic alpha-bungarotoxin receptor and (2) that the
      potencies of nicotinic receptor ligands in the alpha-bungarotoxin binding assay
      were similar to those observed in the functional studies. Northern analysis
      showed that mRNA for alpha 7, a putative nicotinic alpha-bungarotoxin binding
      subunit, and for alpha 5 were present in H69 cells. The present data provide
      further evidence that nicotine increases cell number in small cell lung carcinoma
      and are the first to show that this effect is mediated through an interaction at
      the nicotinic alpha-bungarotoxin receptor population. These results suggest that
      the alpha-bungarotoxin site may be involved in modulating proliferative responses
      in neuroendocrine derived SCLC cells.

PMID- 7812769
TI  - Host resets phase of grafted suprachiasmatic nucleus: a 2-DG study of time course
      of entrainment.
AB  - The object of the present experiment was to examine whether in an intact animal
      implanted with a hypothalamic graft, the phase of the host and grafted
      suprachiasmatic nucleus (SCN) would become synchronized. To this end, we first
      established the time at which daily fluctuations in local cerebral glucose
      utilization were maximal in the SCN in our population of adult hamsters. Next, we
      verified that rhythms of (14C)2-deoxyglucose uptake could be measured on the day
      after birth in pups that were to provide donor tissue. Host and donor animals
      were housed in opposite light:dark cycles. We then transplanted fetal SCN tissue
      into the third ventricle of intact hamsters, placed the grafted animals in
      constant darkness with access to running wheels and examined the phase of
      metabolic activity in host and donor SCN. For several days after grafting, there
      was no circadian fluctuation in the metabolic activity of either the host SCN or
      of the grafted SCN. During this time, the circadian locomotor rhythms were not
      disrupted, suggesting that pacemaker activity was not interrupted. By day 14
      after transplantation, metabolic activity in the host SCN was elevated during
      subjective day and host and donor SCN were in synchrony, invariably with the
      phase of the host animal. We conclude that a signal from the host SCN resets the
      grafted SCN and not vice versa and that pacemaker cells communicate with each
      other rather than exerting independent effects on target sites.

PMID- 7812770
TI  - Pituitary adenylate cyclase-activating polypeptide (PACAP) increases prolactin
      release and tuberoinfundibular dopaminergic neuronal activity.
AB  - Pituitary adenylate cyclase activating polypeptide (PACAP) is a hypothalamic
      peptide that affects anterior pituitary cell function. This study examined the
      effects of PACAP on prolactin (PRL) release in vivo and on tyrosine hydroxylase
      (TH) activity in tuberoinfundibular dopaminergic neurons in vivo and in vitro. In
      ovariectomized rats, intravenous injection of PACAP increased circulating PRL
      levels 3-fold and TH activity in the stalk-median eminence (SME) by 30%.
      Incubation of the SME with 1 microM PACAP in vitro increased TH activity 2-fold.
      Intravenous infusion of ovine PRL (oPRL) by an osmotic mini-pump for 2 days in
      ovariectomized rats increased TH activity in the SME 1.7-fold and reduced
      circulating concentrations of endogenous rat PRL to 20% of control levels. PACAP
      induced a 4-fold rise in endogenous rat PRL levels in oPRL-treated rats and a 30%
      increase in TH activity that was additive to the elevation caused by
      hyperprolactinemia. In suckled lactating rats, PACAP did not alter circulating
      PRL levels or TH activity in the SME. When pups were removed from the dams for 4
      5 h, systemic injection of PACAP stimulated PRL release without altering TH
      activity. However, PACAP, when administered in vitro, stimulated TH activity in
      the SME of lactating rats separated from their pups. These data indicate that
      PACAP may play a role in augmenting PRL release in female rats. The PACAP-induced
      rise in PRL release is modest and not due to a decrease in tuberoinfundibular
      dopaminergic neuronal activity. PACAP increases TH activity in the
      tuberoinfundibular dopaminergic neurons, possibly by a direct action on nerve
      terminals within the median eminence.

PMID- 7812771
TI  - SCG10 mRNA localization in the hippocampus: comparison with other mRNAs encoding
      neuronal growth-associated proteins (nGAPs).
AB  - SCG10 is a nerve growth factor (NGF)-inducible, neuron-specific protein whose
      expression is tightly correlated with axonal and/or dendritic growth. We have
      recently shown that the mRNA encoding SCG10 is expressed at significant levels in
      certain subsets of neurons in the adult rat brain, while its expression is
      undetectable or negligible in other non-neuronal tissues. Here we show that
      regional SCG10 mRNA expression in the adult mouse brain is comparable to that in
      the rat, however, in the hippocampus its expression profile is distinct. In the
      mouse, SCG10 mRNA is expressed at high levels in pyramidal cells of CA3-CA4 sub
      fields of Ammon's horn and at low levels in the CA1-CA2 sub-fields, while it is
      found rather uniformly throughout the pyramidal cell layer of the rat
      hippocampus. SCG10 mRNA is not detectable in the dentate gyrus of the mouse
      hippocampus, although it is expressed in the rat dentate gyrus. Comparison with
      other mRNAs encoding neuronal growth-associated proteins (nGAPs) such as GAP-43,
      MAP2, alpha 1-tubulin and stathmin suggests that dentate granule cells express a
      different repertoire of neuronal growth-associated genes in mouse and rat.

PMID- 7812772
TI  - Non-NMDA receptors in motor neuron disease (MND): a quantitative autoradiographic
      study in spinal cord and motor cortex using [3H]CNQX and [3H]kainate.
AB  - The distribution and density of non-NMDA receptors in spinal cord and motor
      cortex was compared in 10 cases of motor neuron disease (MND) and 8
      neurologically normal controls by quantitative autoradiography using [3H]CNQX and
      [3H]kainate. In the motor cortex of MND cases, an increased density of
      [3H]kainate binding sites was observed which was most marked in the deep layers.
      No significant differences were observed in [3H]CNQX binding in the motor cortex
      between MND and control cases. In the spinal cord significantly increased
      densities of both [3H]CNQX and [3]kainate binding sites were found in the
      substantia gelatinosa and the intermediate grey matter in the MND group. The
      changes in [3H]kainate binding were observed only in the amyotrophic lateral
      sclerosis (ALS) subgroup of MND, while the changes in [3H]CNQX binding in the
      spinal cord were more marked in ALS compared to progressive muscular atrophy
      (PMA) cases. These findings provide evidence in support of a disturbance of
      glutamatergic neurotransmission in MND and suggest that there may be an increased
      excitatory drive to motor neurons via non-NMDA receptors. It is unclear at
      present whether the changes observed represent a compensatory response to loss of
      motor neurons in MND or a pathophysiological phenomenon contributing to motor
      neuron degeneration. Modulation of non-NMDA receptor activity may represent a
      possible target for therapeutic intervention in this disease.

PMID- 7812773
TI  - [3H]D-aspartate binding sites in the normal human spinal cord and changes in
      motor neuron disease: a quantitative autoradiographic study.
AB  - The distribution and density of glutamate transporter sites was determined in
      human cervical and lumbar spinal cord, by quantitative autoradiography using
      [3H]D-aspartate. In the normal human spinal cord (n = 8) there was specific
      binding of [3H]D-aspartate throughout the spinal grey matter, with the highest
      levels observed in the substantia gelatinosa and central grey matter. In the
      ventral horns, particularly at the L5 level, focal hot spots of binding were
      observed in a distribution corresponding to that of lower motor neuron somata.
      Comparison of motor neuron disease (MND) cases (n = 12) with normal controls
      showed a reduction in the density of [3H]D-aspartate binding in the intermediate
      grey matter and the substantia gelatinosa of the lumbar cord. These changes were
      more marked in the amyotrophic lateral sclerosis (ALS) compared to the
      progressive muscular atrophy (PMA) subgroup, and may be due to loss of
      glutamatergic terminals of the corticospinal tract. The changes observed in the
      cervical cord were milder and did not reach statistical significance. No
      differences were found between [3H]D-aspartate binding in the spinal cords of the
      normal controls and a neurological disease control group (n = 6), suggesting that
      the changes observed in MND are disease specific. These findings provide further
      evidence in support of a disturbance of glutamatergic neurotransmission in MND.

PMID- 7812774
TI  - Features of targeted arm movement after unilateral excisions that included the
      supplementary motor area in humans.
AB  - The strategies used to make rapid targeted flexion movements at the elbow were
      assessed for the right and left arms of ten neurologically normal subjects and
      seven patients who had unilateral cortical resections that included all or part
      of one supplementary motor area (SMA). Visual targets were displaced either a
      constant distance (fixed step task) or a variable distance (variable step task).
      The reaction time (RT) for SMA patients as a group did not differ significantly
      from normal, although for some patients, RT exceeded the normal range
      bilaterally. Total movement time (TMT) was longer than normal for the SMA group,
      and again, increased TMTs tended to occur bilaterally. Both groups of subjects
      used a combination of duration and velocity scaling to adjust movement amplitude.
      In normal subjects, however, velocity scaling predominated, whereas in SMA
      patients, duration scaling was increased bilaterally. Our data indicate that the
      initiation of rapid elbow movement to a target presented visually is not
      consistently delayed after lesions that include part of the SMA, but the movement
      speed and strategy used to adjust movement amplitude may be changed bilaterally.

PMID- 7812775
TI  - Effect of oxidative stress on the release of [3H]GABA in cultured chick retina
      cells.
AB  - The effect of ascorbate (1.5 mM)/Fe2+ (7.5 microM)-induced oxidative stress on
      the release of pre-accumulated [3H]gamma-aminobutyric acid ([3H]GABA) from
      cultured chick retina cells was studied. Depolarization of control cells with 50
      mM K+ increased the release of [3H]GABA by 1.01 +/- 0.16% and 2.5 +/- 0.3% of the
      total, in the absence and in the presence of Ca2+, respectively. Lipid
      peroxidation increased the release of [3H]GABA to 2.07 +/- 0.31% and 3.6 +/-
      0.39% of the total, in Ca(2+)-free or in Ca(2+)-containing media, respectively.
      The inhibitor of the GABA carrier, 1-(2-(((diphenylmethylene)amino)oxy)ethyl)
      1,2,5,6-tetrahydro-3-py ridine- carboxylic acid hydrochloride (NNC-711) blocked
      almost completely the release of [3H]GABA due to K(+)-depolarization in the
      absence of Ca2+, but only 65% of the release occurring in the presence of Ca2+ in
      control and peroxidized cells. Under oxidative stress retina cells release more
      [3H]GABA than control cells, being the Ca(2+)-independent mechanism, mediated by
      the reversal of the Na+/GABA carrier, the most affected. MK-801 (1 microM), a non
      competitive antagonist of the NMDA receptor-channel complex, blocked by 80% the
      release of [3H]GABA in peroxidized cells, whereas in control cells the inhibitory
      effect was of 48%. The non-selective blocker of the non-NMDA glutamate receptors,
      6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), inhibited the release of [3H]GABA by
      30% and 70% in control and peroxidized cells, respectively. Glycine (5 microM)
      stimulated [3H]GABA release evoked by 50 mM K+-depolarization in control but not
      in peroxidized cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7812776
TI  - Growth conditions differentially modulate the vulnerability of developing
      cerebellar granule cells to excitatory amino acids.
AB  - The survival of immature nerve cells in a cerebellar culture, predominantly
      excitatory granule cells, is known to be promoted by chronic exposure to high K+
      (> 20 mM) or glutamate (Glu) receptor agonists. These treatments are believed to
      mimic the in vivo effect of the incoming glutamatergic afferents, the mossy
      fibres. Here we report that with maturation the cells become vulnerable to
      excitatory amino acids (EAAs) and that the characteristics of EAA sensitivity are
      dependent on the environmental influences being either "trophic" (25 mM K+ or 140
      microM NMDA, K25 or K10 + NMDA) or "non-trophic" (10 mM K+, K10). Toxicity was
      assayed routinely at 9 days in vitro (DIV) after 24 h exposure to EAAs. Under all
      the tested conditions, the effect of Glu was mediated exclusively through NMDA
      receptors. However, the efficacy and potency of Glu were high in K25- and K10 +
      NMDA-grown cells compared with K10-grown cells. Growth conditions had the same
      influence on NMDA as on Glu-induced toxicity, but with the following special
      features: (1) in comparison with K25 cells, the potency of NMDA was significantly
      lower in K10 + NMDA cells. The K10 + NMDA cultures behaved as if they were
      completely insensitive to the NMDA which is present in their growth medium. (2)
      The K10-grown cells were not vulnerable to NMDA, unless the cell membrane was
      depolarised by shifting the cells into K25 medium. The efficacy of NMDA became
      then similar to that in K25 cultures, although the potency was about 7-fold less.
      Thus NMDA receptors can be activated by the depolarisation of K10 cells, implying
      the operation of Mg2+ blockade of the channel at normal resting membrane
      potential. Although non-NMDA receptors did not seem to be involved in Glu
      toxicity, cells were vulnerable to kainate, which killed significantly more cells
      than Glu (about 80% vs 70%). This was partly due to the resistance of GABAergic
      interneurons present in the cultures to Glu- or NMDA-induced toxicity. In
      contrast to the effects of Glu or NMDA, KA vulnerability was lower in cells grown
      in K25 or K40 than K10 medium (rank order K10 > K25 > K40). Under our
      experimental conditions, cultured cells were resistant to AMPA, quisqualate and
      the selective metabotropic Glu receptor agonist 1S,3R-ACPD. Collectively, the
      observations indicated that EAA sensitivity of cultured cerebellar interneurons
      is significantly and differentially influenced by environmental factors, believed
      to mimic in vivo trophic influences on these cells.

PMID- 7812777
TI  - 6-OHDA-induced lesion of the nigrostriatal dopaminergic neurons potentiates the
      inhibitory effect of 7-OHDPAT, a selective D3 agonist, on acetylcholine release
      during striatal microdialysis in conscious rats.
AB  - Using striatal microdialysis, we attempted to clarify whether or not locally
      infused 7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OHDPAT), a selective D3
      agonist, modulates the basal acetylcholine (ACh) release in conscious rats sham
      operated and lesioned with 6-hydroxydopamine (6-OHDA) into the medial forebrain
      bundle. In the sham-operated rats, 7-OHDPAT at 1 microM decreased ACh release by
      19% of control. In the 6-OHDA-lesioned rats, 7-OHDPAT (0.1-10 microM) decreased
      ACh release in a concentration-dependent manner. The decrease of 37% of control
      was seen at 1 microM 2 weeks after the lesion. The 7-OHDPAT (1 microM)-induced
      decrease was completely antagonized by 1 microM (-)-sulpiride, a D2 and D3
      antagonist, while (-)-sulpiride at 1 microM alone failed to alter ACh release.
      There may exist intrastriatal D3 receptors to inhibit ACh release, and
      supersensitization is evident in a 6-OHDA-lesioned rat Parkinson's model.

PMID- 7812779
TI  - Parvalbumin, calretinin and carbonic anhydrase in the trigeminal and spinal
      primary neurons of the rat.
AB  - The cell-body size of parvalbumin-immunoreactive (-ir) primary neurons was
      measured in the trigeminal (TG) and lumber dorsal root ganglia (DRG). In the DRG,
      parvalbumin-ir was mostly detected in large cells (94% in the range of 600-2800
      microns2). Parvalbumin-ir TG cells were smaller than similar DRG cells and yet
      parvalbumin-ir TG cells of < 400 microns2 (2.86%) were rare. Trichrome stains for
      parvalbumin, calretinin (CR) and carbonic anhydrase (CA), and for parvalbumin,
      calcitonin gene-related peptide (CGRP) and CA were performed to estimate possible
      overlap of these substances. Virtually all parvalbumin-ir DRG cells contained CA
      activity while a small subpopulation (28.5%) of CR-ir DRG cells lacked CA
      activity. All the CR-ir DRG cells that exhibited CA were also ir for parvalbumin.
      31.1% of parvalbumin-ir DRG cells exhibited CR-ir while 71.5% of CR-ir DRG cells
      showed parvalbumin-ir. All the CR-ir DRG cells of < 400 microns2 lacked CA
      activity and parvalbumin-ir while all those of > 800 microns2 exhibited both
      activities. Approximately 30% of CR-ir DRG cells in the size range of 400-800
      microns2 co-expressed CA. DRG cells co-expressing parvalbumin and CGRP were rare
      (approximately 1%). As was the case for the DRG, most of parvalbumin-ir TG cells
      exhibited CA activity (89.24%) and lacked CGRP-ir (96.6%). CR-ir TG cells were
      also subdivided into two groups; one with and the other without co-expression of
      CA. Unlike in the DRG, however, co-expression of parvalbumin and CR could never
      be detected in the TG.

PMID- 7812778
TI  - Visualizing vanilloid (capsaicin) receptors in pig spinal cord by
      [3H]resiniferatoxin autoradiography.
AB  - Autoradiographic mapping using [3H]resiniferatoxin (RTX) revealed high densities
      of vanilloid binding sites over areas (Rexed laminae I and II) in pig spinal cord
      known to be rich in central terminals of capsaicin-sensitive neurons. Also, high
      affinity [3H]RTX binding was detected in membranes obtained from the
      corresponding areas: apparent binding affinity and cooperativity but not the
      maximal receptor density was influenced by the assay conditions (temperature,
      buffer composition). No specific binding could be detected in other areas of the
      spinal cord by either methodology suggesting that the vanilloid receptors are
      present exclusively on central terminals of the capsaicin-sensitive neurons. We
      conclude that [3H]RTX autoradiography may afford a novel neurochemical approach
      to detect localized changes in vanilloid receptor expression.

PMID- 7812780
TI  - CNTF potentiates peripheral nerve regeneration.
AB  - The effect of ciliary neurotrophic factor (CNTF) on peripheral nerve regeneration
      was studied in 6-week-old rats following sciatic nerve transection and
      juxtaposition of proximal and distal stumps. Rats received intraperitoneal
      recombinant human CNTF, 1 mg/kg every other day for 12 days. In all CNTF-treated
      animals, the distribution of the anterograde transport of [3H]leucine-labeled
      material within the distal stump showed a distinct peak activity 21-24 mm distal
      to the nerve transection site. In contrast, the radioactivity in control nerves
      declined rapidly, distributed as proximodistal gradient without a distinct peak.
      In addition, the amount of radioactivity returning from the growing axon tips in
      CNTF was significantly greater than controls. The correlative morphologic studies
      showed a well-advanced stage of myelination in regenerating axons in CNTF
      compared to controls. These combined in vivo correlative kinetic and
      morphological studies indicate that CNTF dramatically potentiates axonal
      regeneration by promoting a greater number of elongating axon tips into the
      distal stump.

PMID- 7812781
TI  - Chronic nicotine treatment counteracts dopamine D2 receptor upregulation induced
      by a partial meso-diencephalic hemitransection in the rat.
AB  - To further elucidate the previously demonstrated protective actions of nicotine
      on lesioned nigrostriatal dopamine (DA) systems (Janson and Moller, Neuroscience,
      57 (1993) 931-941), the present receptor binding experiments were carried out.
      Rats were partially hemitransected at the meso-diencephalic junction and the
      effects of chronic continuous (-)nicotine treatment (osmotic pumps s.c., 0.125
      mg/kg/h, 14 days) on [3H]N-propylnorapomorphine ([3H]NPA) and
      [3H]methylcarbamylcholine ([3H]MCC) binding were investigated in striatal coronal
      sections to study the agonist binding sites of DA D2 receptors and nicotinic
      cholinoceptors, respectively. In saline-treated but not in nicotine-treated rats,
      the lesion led to an increased Bmax value of [3H]NPA binding. The Bmax value of
      [3H]MCC binding was increased by nicotine treatment and decreased by the partial
      hemitransection. These results indicate that chronic nicotine treatment
      counteracts the lesion-induced upregulation of the high-affinity agonist binding
      site of the DA D2 receptor, which may be explained by an increased presence of DA
      via a protective effect of nicotine on neostriatal DA terminals. This action of
      nicotine may be of interest in the treatment of neurodegenerative diseases such
      as Parkinson's disease.

PMID- 7812782
TI  - Glucocorticoids mediate the stress-induced extracellular accumulation of
      glutamate.
AB  - The hippocampal damage caused by stress has been attributed to an increased
      glutamatergic tone brought about by secretion of glucocorticoids. Although
      exposure to stress has been shown to increase the outflow of glutamate, direct
      involvement of glucocorticoid in this phenomenon has not been examined. The
      present study demonstrates that adrenalectomy attenuates the stress-induced
      outflow of glutamate in the hippocampus and prefrontal cortex and that
      glucocorticoid replacement abolishes this attenuation.

PMID- 7812783
TI  - Proliferative effects of humoral factors derived from neuroblastoma cells on
      cultured astrocytes.
AB  - The proliferative effects of humoral factors released from N18-RE105
      neuroblastoma (NRE) cells on cultured astrocytes were assessed in separate co
      culture and conditioned medium studies. In both experimental conditions, the
      humoral factors derived from neuroblastoma cells had growth-promoting effects on
      C6 glioma cells of astroglial lineage, but not on primary cultured astrocytes
      from new-born rat cerebral cortex. It is assumed that neuron-derived humoral
      factors include astroglial growth factors and that differences in responsiveness
      between two kinds of cells are probably related to the stages of astroglial
      maturation processes.

PMID- 7812784
TI  - CuZn-superoxide dismutase (CuZnSOD) transgenic mice show resistance to the lethal
      effects of methylenedioxyamphetamine (MDA) and of methylenedioxymethamphetamine
      (MDMA).
AB  - We have used female and male transgenic (Tg) mice that carry the complete
      sequence of the human copper-zinc (CuZn) superoxide dismutase (SOD) gene in order
      to assess the lethal effects of methylenedioxyamphetamine (MDA) and
      methylenedioxymethamphetamine (MDMA). In contrast to non-Tg mice, both
      heterozygous and homozygous SOD-Tg mice showed resistance to the lethal effects
      of both drugs. Females of both SOD-Tg and non-Tg strains were somewhat more
      resistant to the effects of these drugs in comparison to males. In general,
      homozygous animals show greater resistance to the effects of the two drugs. These
      results suggest that the acute lethal effects of amphetamine-substituted analogs
      might involve the intracellular overproduction of the superoxide radicals
      secondary to hypoxic injury. The gender differences suggest that there might be
      hormonal-free radical scavenger interactions that offer better protection to
      female mice. This might be related both to the lifespan of and to the lower
      prevalence of Parkinson's disease in women. Future studies will need to address
      these issues further.

PMID- 7812785
TI  - Thyrotropin-releasing hormone reverses the supersensitively depressed
      monosynaptic transmission by serotonin in 5,7-dihydroxytryptamine-treated
      neonatal rats in vitro.
AB  - The interaction of serotonin and thyrotropin-releasing hormone (TRH) on
      monosynaptic reflex (MSR) in isolated neonatal spinal cords was examined.
      Superfusion of serotonin (1-30 microM) in untreated cords, depressed the MSR in a
      dose-dependent manner. The depression was about 25% at 10 microM of serotonin, in
      either control or vehicle-treated groups. While for the same concentration of
      serotonin, the depression was 97 +/- 2.1% of the control in cords from 5,7
      dihydroxytryptamine (5,7-DHT)-treated animals. The inhibition of the reflex seen
      in cords obtained from 5,7-DHT-treated animals could not be reversed by washing
      with normal physiological solution (> 60 min) or in presence of serotonin
      antagonists. TRH (0.03-1.0 microM) reversed the depression in a concentration
      dependent manner and complete reversal could be seen with 1 microM of TRH. These
      observations indicate that, serotonin and TRH act dissimilarly on the spinal
      synaptic transmission though they are known to coexist in the descending
      bulbospinal tracts.

PMID- 7812786
TI  - Mutation of low affinity nerve growth factor receptor gene in spontaneously
      hypertensive and stroke-prone spontaneously hypertensive rats: one of the
      promising candidate genes for hypertension.
AB  - There is evidence that abnormal formation of the sympathetic nervous system might
      be important for pathogenesis of hypertension. In the present study we analyzed
      nucleotide sequences of low affinity nerve growth factor receptor (LNGFR) genes
      in the spontaneously hypertensive rat and its stroke-prone substrain. There was a
      point mutation generating an amino acid substitution in signal peptide of these
      LNGFRs. This result suggested that the mutated LNGFR gene is one of the promising
      candidate genes for hypertension.

PMID- 7812787
TI  - Dopamine release in the rat cerebellum and hippocampus: a tissue 3
      methoxytyramine study.
AB  - Multiple lines of evidence indicate dopamine is a neurotransmitter or
      neuromodulator in the cerebellum and hippocampus. In this study, we explored the
      utility of 3-methoxytyramine as an index of dopamine release in these regions. We
      found that: (1) cerebellar and hippocampal 3-methoxytyramine levels can be
      measured by combined gas chromatography-mass fragmentography with negative
      chemical ionization; (2) basal 3-methoxytyramine accumulation rates following
      monoamine oxidase inhibition, but not the steady-state tissue levels, are several
      times lower in these regions than in the frontal cortex; (3) accumulation of 3
      methoxytyramine in the hippocampus and cerebellum can be enhanced following
      electroconvulsive shock, but not acute haloperidol (0.4 mg/kg) treatment. We
      conclude that 3-methoxytyramine accumulation may be a useful index of dopamine
      release in the cerebellum and hippocampus, but dopamine release is regulated
      differently in these regions than in the frontal cortex and striatum.

PMID- 7812788
TI  - Chronic epileptogenicity following focal status epilepticus.
AB  - We examined chronic epileptogenicity in the perforant path stimulation model of
      focal status epilepticus. After 24 h of perforant path stimulation, every
      stimulation elicited multiple population spike discharges, and this phenomenon
      persisted more than 2-3 months after stimulation. Short (10-100 ms) interstimulus
      interval-dependent paired-pulse inhibition was almost completely lost right after
      stimulation, but recovered progressively over the following month. Long (200-1000
      ms) interstimulus interval-dependent paired-pulse inhibition decreased, and in
      spite of a partial recovery, remained significantly reduced 4 weeks after
      stimulation. Frequency-dependent paired-pulse inhibition was lost immediately
      after stimulation. One month later, inhibition at 2 Hz remained significantly
      reduced, although in individual rats recovery ranged from poor to complete.
      Input/output response curves showed increased population spike amplitude but no
      change of the slope of excitatory postsynaptic potentials. 3-4 weeks after
      stimulation, spontaneous generalized motor convulsions were observed in half of
      the stimulated rats. In all of the stimulated rats, the kindling phenomenon was
      significantly accelerated compared with non-stimulated controls, and class 5
      convulsions were elicited in 3.3 +/- 1.0 trials in stimulated rats, against 11.0
      +/- 2.5 trials in controls.

PMID- 7812789
TI  - Cardiovascular and single unit responses elicited by stimulation of the islands
      of Calleja and by changes in arterial pressure.
AB  - Recent experiments in this laboratory have investigated the distribution of the
      nuclear protein Fos in the rat brain after unilateral electrical stimulation of
      the aortic depressor nerve and have revealed intense ipsilateral straining in the
      islands of Calleja. To test the hypothesis that the islands of Calleja may have a
      role in cardiovascular control, we tested the effect on arterial pressure and
      heart rate of microinjection of L-glutamate into the islands of Calleja of the
      artificially ventilated, urethane anesthetized rat. Microinjection of glutamate
      into the islands of Calleja resulted in a decrease in arterial pressure (24.5 +/-
      1.5 mmHg) and heart rate (16.6 +/- 1.6 bpm). These responses were eliminated by
      i.v. injection of propranolol or by transection of the spinal cord at the C1
      level. These results are the first demonstration that the islands of Calleja are
      involved in mediating cardiovascular reflexes primarily through an influence on
      sympathetic outflow to the heart and vessels. To determine the effects of
      increases or decreases of arterial pressure on single unit activity in the
      islands of Calleja, responses of single units in the islands to i.v. injection of
      phenylephrine or sodium nitroprusside were recorded. Of 87 units recorded from in
      the islands of Calleja, 40 (46%) responded to phenylephrine and 27 (68%)
      decreased their firing frequency. Of these 27, 16 (59.3%) increased their firing
      frequency to administration of nitroprusside. In addition, in 11 (31%) of 35
      units recorded from in the islands, glutamate microinjection in the nucleus
      tractus solitarius decreased the firing frequency in 9 (82%) units.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7812790
TI  - Dopamine-induced protection of striatal neurons against kainate receptor-mediated
      glutamate cytotoxicity in vitro.
AB  - The effects of dopamine on glutamate-induced cytotoxicity were examined using the
      primary cultures of rat striatal neurons. Cell viability was significantly
      reduced by exposure of cultures to glutamate or kainate for 24 h. In contrast,
      similar application of N-methyl-D-aspartate (NMDA) or alpha-amino-3-hydroxy-5
      methyl-4-isoxazole-propionate (AMPA) did not induce cytotoxicity. Kainate-induced
      cytotoxicity was significantly inhibited by kynurenate but not by MK-801.
      Dopamine at concentrations of 1-100 microM dose-dependently reduced kainate
      induced cytotoxicity. Forskolin also significantly reduced kainate cytotoxicity.
      The neuroprotective effect of dopamine was antagonized by SCH 23390, a D1
      receptor antagonist, but not by domperidone, a D2 receptor antagonist. Moreover,
      kainate-induced cytotoxicity was prevented by SKF 38393, a D1 receptor agonist,
      or forskolin but not by quinpirole, a D2 receptor agonist. The patch clamp study
      revealed that the same striatal neurons responded to both kainate and NMDA.
      During voltage clamp recording, neither kainate-induced currents nor NMDA-induced
      currents were affected by dopamine. Moreover, dopamine did not affect glutamate-
      or kainate-induced Ca2+ influx measured with fura-2. These findings indicate that
      dopamine prevents kainate receptor-mediated cytotoxicity without affecting the
      kainate receptor activities and intracellular Ca2+ movement. Dopamine-induced
      neuroprotection may be mediated by an increased intracellular cAMP formed
      following activation of D1 receptors.

PMID- 7812791
TI  - Investigations of neurotoxicity and neuroprotection within the nucleus basalis of
      the rat.
AB  - The present study investigated the specific ways by which cytotoxicity due to
      glutamate receptor stimulation could be attenuated by the administration of
      agonists and antagonists of the ionotropic and metabotropic glutamate receptors
      within the nucleus basalis magnocellularis (NBM) of rats as measured by cortical
      choline acetyltransferase activity. The results of these studies suggest that (1)
      the cytotoxicity of ibotenate to NBM cholinergic cells is not dependent upon
      stimulation of metabotropic glutamate receptors, but results from activation of N
      methyl-D-aspartate (NMDA) receptors, (2) the cytotoxicity of quisqualate to
      cholinergic cells within the NBM is not dependent upon stimulation of NMDA or
      metabotropic receptors, and (3) the cytotoxicity of NMDA was prevented by
      administration (i.p.) of the un-competitive NMDA antagonist memantine (30 mg/kg),
      resulting in plasma levels of 2.5 micrograms/ml, a concentration known to block
      efficiently NMDA receptors in vitro. Finally, performance of a food-motivated,
      delayed-alternation task on a T-maze was impaired by injections of NMDA into the
      NBM, but was prevented by co-administration of NMDA with memantine.

PMID- 7812792
TI  - Expression of protein phosphatases (PP-1, PP-2A, PP-2B and PTP-1B) and protein
      kinases (MAP kinase and P34cdc2) in the hippocampus of patients with Alzheimer
      disease and normal aged individuals.
AB  - Microtubule-associated protein tau is abnormally hyperphosphorylated in the brain
      of patients with Alzheimer disease (AD). Previous studies have shown (i) that in
      vitro tau can be phosphorylated to an Alzheimer abnormally phosphorylated state
      like protein by proline-directed protein kinases MAP kinase and p34cdc2, and (ii)
      that the AD abnormally phosphorylated tau can be in vitro dephosphorylated by
      protein phosphatases PP-2B, PP-2A and PP-1 and not by PP-2C. However, to have a
      direct effect on the regulation of phosphorylation of tau, these enzymes should
      be present in the affected neurons. In the present study immunocytochemical
      localization of protein phosphatases PP-1, PP-2A, PP-2B and PTP, and protein
      kinases MAP kinase and p34cdc2 were studied in the hippocampal formation of AD
      and as a control in non-demented elderly patients. All the protein phosphatases
      and protein kinases studied were localized to both granular and pyramidal
      neurons. In the pyramidal neurons, the enzymes staining was observed in neuronal
      soma and neurites. PTP-1B, PP-1 and PP-2A were also highly expressed in
      microglia. The topographical distributions of all the enzymes studied were
      similar, i.e. the intensity of immunostaining in hippocampus in end-plate (CA3
      and CA4) > prosubiculum, subiculum > entorhinal cortex > dentate gyrus > CA2 >
      CA1. Furthermore, the expression of all the enzymes was also observed in the
      tangle-bearing neurons. The PP-2B staining of the tangle-bearing neurons was
      weaker than the unaffected neurons in the same tissue section field in AD cases.

PMID- 7812793
TI  - Glucose attenuates a morphine-induced decrease in hippocampal acetylcholine
      output: an in vivo microdialysis study in rats.
AB  - Systemic injections of morphine impair performance in memory tests. Glucose
      administration ameliorates memory deficits produced by morphine treatment. The
      memory impairments induced by morphine may be related to opioid inhibition of
      acetylcholine release with reversal of this effect by glucose. The present
      experiment determined whether: (1) systemic morphine treatment decreases
      acetylcholine output in the hippocampal formation; and (2) systemic glucose
      administration attenuates the effect of morphine treatment. Employing
      microdialysis, samples were collected at 12-min intervals and assayed for
      acetylcholine using HPLC with electrochemical detection. Morphine (10
      mg/kg)/saline injections resulted in an immediate decrease in acetylcholine
      output (20-35%) that was observed up to the third postinjection sample (36 min).
      Glucose (100 mg/kg) administered concurrently with morphine attenuated the
      reduction in acetylcholine output in the second and third samples. These findings
      suggest that glucose may attenuate morphine-induced memory impairments by
      reversing a decrease in acetylcholine output produced by morphine.

PMID- 7812794
TI  - Bilateral changes in striatal dopamine metabolism after unilateral intracarotid
      and intrastriatal administration of apomorphine.
AB  - Following cannulation of the common carotid artery of female Sprague-Dawley rats,
      3 microCi (10 micrograms) of [3H]apomorphine were infused. At various time
      intervals, drug concentrations were determined in the right and left striata,
      anterior forebrains, posterior forebrains and cerebella. One minute following
      intracarotid infusion of apomorphine, approximately a 65-fold right/left
      difference in apomorphine concentrations was attained in all forebrain
      structures, and this difference steadily diminished with time as a result of
      declining drug levels in the infused hemisphere. The concentrations of dopamine
      and its metabolites (DOPAC, HVA and 3-MT) were quantified by gas chromatography
      mass spectrometry in the right and left striata at 5 and 15 min after unilateral
      intracarotid infusion of 1 microgram apomorphine. At both time intervals and
      regardless of the side infused, the metabolites of dopamine increased ipsilateral
      to the side of infusion. Moreover, 3-MT levels were significantly decreased in
      the contralateral striatum. After direct intrastriatal injection of either 0.1 or
      1.0 microgram apomorphine into the right striatum, the levels of dopamine
      metabolites were again increased in the ipsilateral striatum. 3-MT levels were
      also decreased significantly in the left striatum. In contrast to the effects
      observed after systemic administration of apomorphine, these results demonstrate
      that dopamine release in the striatum is increased by selectively delivering
      higher concentrations of apomorphine to the nerve terminals of the nigrostriatal
      neurons. The effects of unilateral apomorphine on dopamine metabolism in the
      contralateral striatum are most likely the effect of interhemispheric
      communication.

PMID- 7812795
TI  - Kynurenate is neuroprotective following experimental brain injury in the rat.
AB  - Pharmacologic inhibition of excitatory amino acid neurotransmission improves
      physiologic, metabolic, and neurobehavioral outcome following experimental brain
      trauma. However, no studies to date have demonstrated pharmacologically-induced
      attenuation of histopathological changes associated with experimental brain
      injury models. The present study examined the effects of kynurenate, an NMDA and
      non-NMDA receptor antagonist, on neuronal survival in the hippocampus after
      lateral fluid-percussion brain injury in the rat. Animals (n = 10/treatment)
      randomly received an intravenous injection of either kynurenate (300 mg/kg) or
      buffer (equal volume) 15 min following fluid-percussion brain injury of moderate
      severity. Two weeks after injury, animals were sacrificed and neuronal cell loss
      in the hippocampus was examined with Nissl staining. Selective loss of neurons in
      the CA3 region of the hippocampus, which has previously been characterized in
      this model of brain injury, was found to be significantly attenuated following
      kynurenate treatment (P < 0.05). These data suggest that pharmacologic compounds
      which are known to have beneficial effects on neurobehavioral and physiological
      outcome following brain injury may also significantly attenuate post-traumatic
      neuronal cell loss. Our results also support other recent data that
      pharmacological intervention with an excitatory amino acid receptor antagonist
      may be of therapeutic value in the treatment of brain injury.

PMID- 7812796
TI  - The monoclonal antibody Alz-50, used to reveal cytoskeletal changes in
      Alzheimer's disease, also reacts with a large subpopulation of somatostatin
      neurons in the normal human hypothalamus and adjoining areas.
AB  - The monoclonal antibody Alz-50 is directed against Alzheimer's disease-related
      modified tau proteins and reveals cytoskeletal changes, i.e. neurofibrillary
      tangles and dystrophic neurites. The present study shows that, in the
      hypothalamus of non-demented control subjects, this same antibody gives a
      distinctive staining pattern of a subpopulation of somatostatin neurons and
      beaded fibres. Furthermore, Alz-50 occasionally recognizes somatostatin
      containing cell bodies and dystrophic neurite-like fibers in the (neuritic)
      senile plaques of AD patients. These observations have direct consequences for
      the interpretation of Alz-50 staining in diagnostic usage and for the assessment
      of Alzheimer's disease-like changes induced by beta-amyloid in experimental
      animal brains. On dot spotting, Alz-50 was found to bind to a number of fragments
      from the somatostatin precursor, of which somatostatin 15-28 stained best.
      Preadsorption of Alz-50 by somatostatin 15-28, as well as other specificity
      tests, failed, however, to provide any clue to the nature of the unknown
      compound(s) stained in the control hypothalamus.

PMID- 7812797
TI  - The effect of sweeteners on bitter taste in young and elderly subjects.
AB  - The purpose of this study was to quantify the degree of reduction in perceived
      bitterness by sweeteners at both threshold and suprathreshold concentrations of
      bitter compounds. Detection and recognition thresholds were determined for six
      bitter compounds (caffeine, denatonium benzoate, magnesium chloride, quinine
      hydrochloride, sucrose octaacetate, and urea) in the absence and presence of
      several suprathreshold concentrations of five sweeteners. The sweeteners were:
      sucrose, aspartame, sodium saccharin, mannitol, and sorbitol. Polycose was also
      tested along with the sweeteners. The degree to which bitter thresholds were
      affected by the addition of sweeteners was dependent on the chemical
      classification of the sweeteners and their concentrations. In general, the
      natural sweeteners, sucrose, mannitol, and sorbitol, were more effective than the
      noncaloric sweeteners, aspartame and sodium saccharin, in elevating the detection
      and recognition thresholds of the bitter compounds. A sweetness intensity
      approximating that of 6% sucrose (0.175 M sucrose) or greater was required to
      elevate thresholds. For elderly subjects, sweeteners did not significantly
      elevate thresholds for denatonium benzoate and sucrose octaacetate. The degree to
      which sorbitol and sucrose can decrease the perceived bitterness intensity of
      suprathreshold concentrations of the six bitter compounds was also determined.
      The concentrations of sweeteners and bitter compounds were selected to be of
      moderate to high subjective intensity. The levels of sweeteners used in the
      mixtures were: sucrose (none, 0.946 M, and 2.13 M) and sorbitol (none, 2.1 M, and
      3.68 M). Both sweeteners significantly reduced the bitterness ratings of almost
      every concentration of the six bitter compounds. The greatest reductions in
      bitterness were 87.0% for 0.192 microM denatonium benzoate mixed with 2.13 M
      sucrose and 84.7% for 1.8 M urea mixed with 3.68 M sorbitol.

PMID- 7812798
TI  - Use of [3H]5,7 dichlorokynurenic acid to identify strychnine-insensitive glycine
      receptors in human postmortem brain.
AB  - [3H]5,7 Dichlorokynurenic acid ([3H]DCKA) was used to define conditions for
      obtaining selective binding to strychnine-insensitive glycine receptors. The
      parameters were established in sections of human brain prior to localizing the
      receptors sites by autoradiography. The binding of [3H]DCKA was of high affinity
      (Kd = 14.5 nM), readily reversible (K-1 = 0.216 min-1), and specific (60%
      specific binding determined by inhibition with 100 microM glycine or D-serine).
      High levels of strychnine-insensitive glycine receptors were identified in
      several brain areas including portions of the cerebral cortex (Bmax in middle
      temporal gyrus: 174.0 fmol/mg tissue), basal ganglia, hippocampal formation, and
      midbrain. These results identify regions where glycine receptors may be involved
      in modulating NMDA-mediated channel activity.

PMID- 7812799
TI  - Chromogranin A applied to the nucleus accumbens decreases locomotor activity
      induced by activation of the mesolimbic dopaminergic system in the rat.
AB  - The aim of the study was to obtain supporting evidence, using a behavioral
      paradigm, of the hypothesis that chromogranin A attenuates transmitter release in
      the CNS. We studied the effects of chromogranin A injected into the nucleus
      accumbens on locomotor activity triggered by application of picrotoxin into the
      ventral tegmental area of rats. Injection of picrotoxin into the ventral
      tegmental area, which is known to disinhibit dopaminergic mesolimbic neurons,
      caused a significant increase in horizontal activity. Distance covered during
      locomotion and movement time increased more than twofold, whereas stereotypy time
      and number, indices of nonlocomotor behavior, were not significantly affected by
      picrotoxin. Pressure injection of chromogranin A into the nucleus accumbens prior
      to injection of picrotoxin into the ventral tegmental area prevented these
      locomotor effects and had little or no effect on nonlocomotor behavior.
      Similarly, the picrotoxin-induced activity was prevented by injecting cobalt
      chloride into the nucleus accumbens. The results show that chromogranin A has an
      attenuating effect, either directly or indirectly, on dopaminergic
      neurotransmission in the nucleus accumbens that can be exemplified by inhibiting
      picrotoxin-induced locomotor activity. Further studies are needed to determine
      the mechanism of chromogranin A action in the nucleus accumbens.

PMID- 7812800
TI  - AF64A affects septal choline acetyltransferase but not parvalbumin immunoreactive
      cells.
AB  - Rats received bilateral intracerebroventricular (ICV) infusions of either AF64A
      (1.5 nmol/ventricle; n = 9) or vehicle (3.0 microliters/ventricle; n = 7). Four
      weeks later, the animals were anesthetized and their brains processed to
      visualize and quantify choline acetyltransferase (ChAT) immunoreactive (IR) and
      parvalbumin-IR GABAergic neurons in the septal complex by immunocytochemistry
      (PAP method). AF64A significantly reduced the number of ChAT-IR perikarya in the
      medial septum (28%), ventral limb of the diagonal band of Broca (30%), and
      horizontal limb of the diagonal band of Broca (20%), but did not affect the
      number of parvalbumin-containing GABAergic neurons in any of the septal
      subdivisions. These results provide further evidence that AF64A is a selective
      cholinotoxin.

PMID- 7812801
TI  - Topographical organization of subicular neurons projecting to subcortical
      regions.
AB  - Direct projections from the subiculum to the septum, thalamus, and hypothalamus
      were studied in the rat by the fluorescent retrograde double-labeling technique
      with Fast blue and Diamidino yellow. The results confirm and extend the
      previously reported findings. The dorsal subiculum projects primarily to the
      lateral septum, anterior and midline thalamus, and mammillary complex. The
      distribution areas of cell bodies of these projection neurons are substantially
      segregated, depending on their target region, and few single neurons project to
      two of the target regions by way of axon collaterals. The ventral subiculum
      projects mainly to the lateral septum, midline thalamus, and ventromedial
      hypothalamic area. The distribution areas of cell bodies of these projection
      neurons are considerably overlapped with one another, and a number of single
      neurons send axon collaterals to two of the lateral septum, midline thalamus, and
      ventromedial hypothalamic area. It is, thus, indicated that the populations of
      subicular neurons projecting to each of the subcortical structures examined are
      more distinctly segregated in the dorsal subiculum than in the ventral subiculum.

PMID- 7812802
TI  - Role of proprioceptors in the mylohyoid muscle.
AB  - Afferent discharges of the mylohyoid muscle branch during respiration were
      studied electrophysiologically in the rat. Afferent discharges from the mylohyoid
      muscle branch of the mylohyoid nerve were found to be synchronized with
      respiration. Stretching of the mylohyoid muscle elicited afferent discharges of
      the mylohyoid muscle branch, suggesting that lengthening of the mylohyoid muscle
      caused electrical activity in the proprioceptors. When the central cut end of the
      mylohyoid muscle branch was stimulated electrically, reflex discharges were
      recorded from the EMG lead at the sternohyoid muscle where it is innervated by
      the cervical nerve. The latency between the electrical stimulation and the action
      potential in the sternohyoid muscle was 3-4 ms. Therefore, the mylohyoid muscle
      branch may transmit information to the sternohyoid muscle regarding the
      stretching actions of the mylohyoid muscle resulting from movements of the hyoid
      bone.

PMID- 7812803
TI  - Neuronal activity in the midline thalamic nuclei during Pavlovian heart rate
      conditioning.
AB  - Multiple unit activity (MUA) was recorded from chronically implanted electrodes
      in the midline nuclei of the thalamus in rabbits receiving either Pavlovian heart
      rate (HR) conditioning, or explicitly unpaired presentations of the conditioned
      stimulus (CS) and unconditioned stimulus. Animals receiving paired training
      demonstrated increases in CS-evoked MUA compared to animals receiving unpaired
      training; however, these increases were small and only weakly correlated with the
      HR conditioned response, suggesting that the midline nuclei are only minimally,
      if at all, involved in associative learning.

PMID- 7812804
TI  - Stimulatory effects of bombesin-like peptides on hypothalamic arcuate neurons in
      rat brain slices.
AB  - The effects of bombesin, gastrin-releasing peptide, neuromedin C, ranatensin, and
      neuromedin B on hypothalamic arcuate neurons were tested in this study using
      extracellular single-unit recording in fresh brain tissue slices. Adult
      ovariectomized Sprague-Dawley rats were used for preparation of brain slices. All
      bombesin-like peptides in pmol ranges exhibited potent stimulatory effects on the
      firing of arcuate neurons, i.e., gastrin-releasing peptide stimulated 90.9% (n =
      22), bombesin 78.0% (n = 41), neuromedin C 63.2% (n = 19), ranatensin 58.0% (n =
      22), and neuromedin B 50.0% (n = 6) of arcuate neurons tested. Pretreatments with
      either [Leu13-psi(CH2NH)-Leu14]-bombesin or [D-Phe6,Des-Met14]-bombesin6-14
      ethylamide, two bombesin antagonists, significantly blocked most of the actions
      of bombesin-like peptides tested. The present results further support the notion
      that bombesin-like peptides may play a significant role in the arcuate nucleus.

PMID- 7812806
TI  - Sodium nitroprusside modulates NMDA response in the rat supraoptic neurons in
      vitro.
AB  - The modulatory effects of NO on N-methyl-D-aspartate (NMDA)-induced response in
      neurons of the supraoptic nucleus (SON) were studied by intracellular recording
      and radioimmunoassay of cyclic nucleotides using the rat brain slice preparation.
      Depolarization induced by 100 microM NMDA was reduced by application of 1 to 3 mM
      of the NO-donors, sodium nitroprusside, and isosorbide dinitrate in all 8 neurons
      and in 6 of 10 neurons, respectively. The scavenger for NO, hemoglobin, and the
      inhibitor of NO synthase, NG-nitro-L-arginine (LNNA) enhanced the NMDA-induced
      depolarization in four neurons and two of three neurons, respectively.
      Intracellular cGMP accumulation induced by NMDA was significantly diminished by
      LNNA. However, NMDA-induced depolarization was not affected by either the protein
      kinase inhibitor, N-[2-(methylamino)ethyl]-5- isoquinolinesulfonamide
      dihydrochloride (H-8), or the phosphodiesterase inhibitor, 3-isobutyl-1
      methylxanthine (IBMX). These results indicate that NO reduces NMDA-induced
      depolarization in a manner that is independent of cGMP and may control the
      activity of the SON neurons through NMDA receptors.

PMID- 7812805
TI  - Ischemic tolerance and extracellular amino acid concentrations in gerbil
      hippocampus measured by intracerebral microdialysis.
AB  - Preconditioning of the brain with sublethal ischemia induces tolerance to
      subsequent longer periods of ischemia. To elucidate the role of excitatory and
      inhibitory amino acids in the induction of ischemic tolerance, we measured the
      extracellular concentrations of the amino acids in the gerbil hippocampus with
      intracerebral microdialysis. Mongolian gerbils were subjected to 3 min of
      forebrain ischemia 4 days after preconditioning with 2 min of ischemia or sham
      operation. Microdialysis probes were implanted into the hippocampus before the
      second ischemia and the amino acid concentrations in the dialysates were measured
      with HPLC. During and immediately after 3 min of ischemia without
      preconditioning, the concentrations of glutamate, glycine, gamma-aminobutyric
      acid, and taurine, but not glutamine, increased significantly. The increased
      amino acid levels rapidly returned to baseline after reperfusion. Preconditioning
      of the brain did not alter the amount of any amino acid released during and after
      the second ischemia. The excitotoxic index also unchanged in the preconditioned
      hippocampus. Thus, the results clearly show that ischemic tolerance is not
      induced through the alteration of the amounts of excitatory and inhibitory amino
      acids released during subsequent ischemia.

PMID- 7812807
TI  - Chronic implantation technique for monopolar EEG monitoring of epileptic seizures
      in mice.
AB  - The implanted system was composed of four silver ball electrodes placed in the
      burr hole of the skull, a reference placed subcutaneously near the nose, two
      electrodes for EMG, and a ground. The dural attachment was 0.1 mm in diameter. A
      cassette connector was placed on the back. Implanted cables between the cassette
      connector and all electrodes consist of twisted fine wires placed in a silicone
      tube 0.5 mm in diameter. The implanted electrode system weighed 0.8 g. The outlet
      cables were of the same materials used for implanted cables and placed in a
      silicone tube 1.5 mm in diameter. The impedance matching between these cables was
      successful and assured the minimum contamination of artifacts in the EEG
      recording of freely moving mice. Long-term (4-5 weeks) recording, thus, became
      possible without damage to the implanted materials. Monopolar recordings
      demonstrated the localized paroxysmal discharges during general tonic clonic
      convulsion in El mice. Several artifacts are presented.

PMID- 7812808
TI  - Cytochrome oxidase activity in the lateral geniculate nucleus of postnatal rats.
AB  - We have studied the cytochrome oxidase activity and its pattern of distribution
      in the dorsal lateral geniculate nucleus of the rat during postnatal development.
      Between the 1st and the 8th postnatal days, the geniculate nucleus is seen to
      have a homogeneous enzymatic pattern with high neuronal density and moderately
      reactive neuropil. On the 15th postnatal day, different levels of neuronal
      enzymatic activity are found, and adult morphology is attained as of the 21st.
      The densitometric study has revealed that moderate and lightly reactive neurons
      are predominant between the 1st and the 8th postnatal days, whereas dark neurons
      are more numerous and optical density maximum on the 15th postnatal day. No
      variation in the enzymatic pattern was observed between the 21st and the 42nd
      days.

PMID- 7812809
TI  - Influence of halothane and methoxyflurane on regional brain and spinal cord
      concentrations of methionine-enkephalin in the rat.
AB  - Rats were exposed to either oxygen (controls), 1.5% halothane in oxygen, or
      methoxyflurane (0.5%) in oxygen over a period of 2 h, then sacrificed at the end
      of exposure (2-h group), 4 h after removal from environmental chamber (4-h
      group), or at 24 h following anesthetic exposure (24-h group). Pituitary
      (excluding the neural lobe, Pit), brain, and spinal cord areas were isolated and
      processed with Met-enkephalin tissue concentrations determined. In halothane
      exposed animals, Met-enkephalin concentrations in pit and across CNS areas
      studied were significantly lower at 2 h following anesthetic exposure than in
      control animals. Concentrations of Met-enkephalin in many areas of CNS and Pit of
      4-h group approached control levels. Concentrations of Met-enkephalin in all
      areas studied except spinal cord returned to basal levels by 24 h following
      halothane exposure. Exposure to methoxyflurane resulted in less dramatic changes
      in Met-enkephalin concentrations across CNS regions examined. Exposure to
      methoxyflurane resulted in significant decreases in Met-enkephalin levels in
      olfactory bulb, thalamus, and hippocampus only. Met-Enkephalin levels did not
      change significantly in other areas of the central nervous system following
      methoxyflurane exposure. These results indicate that halothane and methoxyflurane
      may have differential effects on the endogenous opioid system.

PMID- 7812810
TI  - A quick silver method for senile plaques and neurofibrillary tangles in paraffin
      sections.
AB  - A new silver method for senile plaques and neurofibrillary tangles (NFT) in
      paraffin sections is presented. This new technique is rapid in execution (15 min)
      and reveals senile plaques of all morphological types as well as NFT. The silver
      staining is spatially congruent with immunocytochemical staining for the beta
      amyloid peptide (A beta) in adjacent sections.

PMID- 7812811
TI  - [DNA analysis in classic phenylketonuria--screening for mutations and haplotype
      analysis in Slovak families].
AB  - Authors in this contribution present the results of screening for mutations in
      PAH gene responsible for classical phenylketonuria (PKU), and that of haplotype
      analysis, based on DNA analysis in 49 Caucasian families with at least one
      affected child from Slovak Republic. The clearly predominant PKU mutation in this
      population was the R408W with proportion of 45.9% among all PKU mutations. In
      addition four other mutations have been identified: IVS12nt1-10.2%, R158Q-7.1%,
      R261Q-7.1%, and R252W-2.0%. the overall proportion of identified PKU mutations
      equals 72.4%. Considering the fact, that these mutations are amenable to rapid
      and rather simple detection using PCR, the DNA analysis is recommended as a
      method of direct diagnosis in clinical practice as well as in prevention.

PMID- 7812812
TI  - The antihypertensive treatment and high-resolution electrocardiography.
AB  - After six months of antihypertensive treatment the regression of the initially
      present myocardial hypertrophy was observed: The decrease in blood pressure
      values is in correlation with the regression of the left ventricular hypertrophy.
      No correlation with parameters of high-resolution electrocardiography was noted.
      In one patient, a deterioration of late potentials was observed. It became more
      pronounced following the treatment. The monitoring of antihypertensive treatment
      effects by echocardiography and high-resolution electrocardiography may be
      therefore considered useful, especially in expected regression of the left
      ventricular hypertrophy. In individual cases of very outstanding regression,
      there exists the potential possibility of the process, resulting in the risk of
      arrhythmogenic substrate formation and subsequent generation of dysrhythmias.

PMID- 7812814
TI  - [Relation between the heart and lungs in children and adolescents with
      ventricular septal defects].
AB  - Lung function tests were performed in 39 patients with haemodynamically
      significant ventricular septal defect (age 3-20 years, median 10 years). We found
      pulmonary restriction in 47% of patients, pulmonary hyperinflation in 50% of
      patients, obstruction of smaller airways in 20% of patients preoperatively.
      Observed lung function disorders were not related to the volume of the left to
      right shunt and the mean pulmonary arterial pressure. The surgical correction of
      VSD lead only to significant improvement of hyperinflation. The rest abnormal
      findings persisted for several years postoperatively. We conclude that the
      surgical repair of significant ventricular septal defect beyond 9.5 years of age
      does not prevent chronic lungs changes. The clinical implications of these
      findings yet remain to be established.

PMID- 7812813
TI  - [Metaphylaxis and treatment of cystine lithiasis--personal experience].
AB  - The authors presented their own experience with treatment of cystine lithiasis in
      7 patients, which has been performed during the course the past of ten years.
      Identification of cystine was performed by concrement submitted examination,
      using a polarizating microscope, and x-ray difractometric structural analysis.
      After stone extraction the patients were treated by a high fluid intake (diuresis
      over 2.5 l), alcalizating treatment involving citrates (Alkalit Spofa), and
      Penicilamin (Spofa), or Thiola (Santen) which are currently proved to be the most
      optimal approach. Recurrence of stones requiring percutaneous treatment, was
      observed in one of the patients during five years metaphylaxy. Another patient of
      the same group had three times stated cystine stone recurrence which passed
      spontaneously.

PMID- 7812815
TI  - [Monitoring genotoxicity in the environment using cytogenetic methods such as
      chromosome analysis of peripheral lymphocytes, sister chromatid exchange and the
      micronucleus test].
AB  - The work's aim is to observe environmental genotoxicity in the town of Ruzomberok
      and its surroundings in relation to the control group. The authors used three
      cytogenetic methods and compared their mutual sensitivity: chromosome analysis of
      human peripheral lymphocytes (CAHPL), micronuclear test (MN test) and
      differential staining of sister chromatides (SCE). The authors examined four
      groups of 30 children from the age of 6 to 8 years, originating from the
      localities of Cernova-Hrboltova, Stiavnica-Ludrova and Sliace. Individual
      localities are in various distances from the source of pollution (the industrial
      sewage treatment plant-STP and cellulose and paper factory-CPF). The control
      group contained children from the suburbs of Martin where no impact of industrial
      exhalations was assumed. For the purpose of evaluation of cytogenetic analysis
      results, nonparametric tests (K-S test and Z test) were used. The most sensitive
      method fo those used by the authors for the purpose of genotoxicity evaluation is
      CAHPL. The SCE method is less sensitive than CAHPL, but still more sensitive than
      MN test and suitable as a supplementary method for detection of exposition to
      genotoxic substances.

PMID- 7812816
TI  - [Surgical treatment of insulinoma].
AB  - The paper summarizes experience with diagnosis and surgical treatment of
      insulinomas of the pancreas. Experience with three patients subdued to surgical
      treatment at the Department of Surgery of F.D. Roosevelt Hospital in Banska
      Bystrica confirm the rules of effective treatment of insulinomas: importance of
      neurological symptoms in early diagnosis, importance of angiography as the best
      method for localization of insulinomas in comparison with ultrasonography and CT.
      In addition, algorithm of the surgical treatment of insulinomas together with the
      specificity of the surgical technique were confirmed.

PMID- 7812817
TI  - [31P NMR spectroscopy in acute experimental pancreatitis].
AB  - In order to investigate the changes in phosphoglucose metabolism in acute
      experimental pancreatitis, the authors utilized the measuring cell NMR
      spectroscopy. The experimental pancreatitis had been evoked by both the method of
      ligature of lateral pancreas ducts and that of the duodenal blind loop. These
      methods evoke a morphological response, namely edematous and necrotizing
      pancreatitis. Gradual reduction of macroergic phosphate binds and augmentation of
      anorganic phosphates represent the principal change in NMR spectrum. The clinical
      picture provides evidence of the exhaustion of highly energetic phosphate
      compounds which are necessary for the maintenance of integrity of the pancreas
      tissue in acute experimental pancreatitis. The discussion includes the
      possibilities and limitations of the NMR spectroscopy.

PMID- 7812818
TI  - [Medical and economic advantages of percutaneous transluminal angioplasty].
AB  - Percutaneous transluminal angioplasty (PTA) has been used for nearly 30 years.
      This method was refused in the past because of lack of knowledge of its
      effectiveness, and insufficient technical equipment for its safe realization. The
      further factor negatively affecting usage of this method in common clinical
      practice in occlusive diseases of the lower limbs arteries was an essentially
      shorter long-term patency than that after reconstructive arterial surgery.
      Currently this method is widespread in common clinical practice and with the help
      of angioscopy, argon-laser angioplasty and rotary transluminal catheter system
      (RO-TACS) it can still be improved. In this study the authors deal in detail with
      medical and economical advantages of this widely used method.

PMID- 7812819
TI  - [The role of serotonin in the regulation of the immune response].
AB  - The author presents in her study the currently known serotonin effects on the
      immunity system, and the possibility of medicamentous utilization of agonists and
      antagonists of serotonin receptors in order to elucidate the effect of the 5-HT
      immunomodulating mechanism. 5-HT affects the antibody formation in sense of its
      reduction, the formation being evoked by antigenic stimuli. The mechanism
      involved however, is not entirely clear. The particular receptor being co
      responsible in DNA synthesis inhibition is 5-TH1. The reduction of MHC-antigens
      expressiveness, which takes place due to serotonin, is intermediated by the
      classical 5-HT2 receptor. The procedure takes place in cooperation with 5-HT1A
      receptor. The serotonin induced augmented NK cells cytotoxicity is specifically
      mediated by 5-HT1 receptor. The participation of serotonin is assumed in
      pathogenesis of various diseases, there is however, relatively little knowledge
      about its effect on immunity system.

PMID- 7812820
TI  - [The Slovak Medical Library].

PMID- 7812822
TI  - [NK cells and their characteristics and immunogenetic aspects].
AB  - This review summarizes knowledge of history and development of the "new"
      biological phenomenon. NK cells play a pivotal role in immune surveillance
      against tumors and virus-infected cells. They are also involved in natural
      resistance to bone marrow transplantations and in the regulation of the growth
      and activity of immunocompetent and hematopoietic cells. Unlike cytotoxic T
      lymphocytes NK cell activity is not dependent on thymus maturation and an
      expression of class I MHC antigens. They lack immunological memory and develop
      directly from precursor cells of the bone marrow. The lytic activity of NK cells
      is associated with the population of large granular lymphocytes (LGL). In human
      peripheral blood there is about 5% of LGL. A great deal of the study is given to
      still actual about the possible role of class I MHC antigen expression in
      regulation of NK-cell cytotoxicity. (Fig. 1, Tab. 2, Ref. 118).

PMID- 7812823
TI  - [Effectiveness of laparoscopic cholecystectomy using various surgical
      techniques].
AB  - The study compares two groups, both in number of 100 patients subdued to
      laparoscopic cholecystectomy. In each group a different surgical technique was
      performed. The comparison study regarded duration of surgical performance,
      incidence of postoperative complications, surgical morbidity and mortality, as
      well as duration of hospitalization and return to full activity. The surgical
      interventions were performed at two distinct workplaces. Neither of the mentioned
      parameters yielded significant differences in dependence on the utilized
      operation technique. The entire group of 200 cholecystectomic performances was
      thereafter compared with a comparable group of classical cholecystectomies which
      had been performed at the identical hospitals. The mentioned parameters yield
      statistically significant differences in postoperative morbidity, hospitalization
      duration and return to full professional activity. The results speak in favour of
      laparoscopic cholecystectomy. The duration of surgical performance, number of
      postoperative complications requiring reoperation, and mortality do not yield
      significant differences. The comparison of the observed parameters in relation to
      age categories presents laparoscopic cholecystectomy as the method suitable also
      for older patients above 65 years of age. (Tab. 2, Fig 2, Ref. 6).

PMID- 7812821
TI  - [The role of antioxidants in the prevention of cardiovascular diseases].
AB  - The potential role of natural antioxidants (vitamin C--ascorbic acid, vitamin E-
      tocopherols, carotenoids and selenium) in the prevention of cardiovascular
      diseases is reviewed. It is probable that free oxygen radicals and oxidatively
      modified particles of low-density lipoproteins (LDL) participate in the
      development of atherosclerotic lesions. A great number of experimental, cross
      sectional, retrospective and prospective epidemiological studies found a
      substantial increase of the risk of ischemic heart disease and stroke in
      individuals and populations with low intake of antioxidants from diet. Extremely
      high cardiovascular mortality in Slovakia and other postcommunist countries could
      be only partially explained by "classical" risk factors (hypertension,
      hypercholesterolemia and smoking). In the communist European countries there was
      a high consumption of spirits, cigarettes and salt, polluted environment and low
      consumption of the chief source of antioxidants--fruits. In these countries
      emphasis should be given to the prevention of antioxidant deficiencies by the
      increase of fruit and vegetable consumption, and to the decrease in salt, spirit,
      cigarettes and saturated fat consumption.

PMID- 7812825
TI  - [Psychosomatic aspects in dermatology].
AB  - The study presents a review about the influence of psychical factors in
      dermatology and their participation in origination of psychosomatic skin
      diseases. The skin is the visibly organ which reflects psychosomatic influences,
      and displays acute sensation processes. Psychical factors participate in
      origination of skin disease, their course and eventual recurrence. (Ref. 15.)

PMID- 7812824
TI  - [Corium transplantation in reconstruction of ventral hernias].
AB  - The authors present a group of 28 patients who after utilization of corium grafts
      were analyzed by means of a retrospective fill-in-form method. The most frequent
      plastic surgery is s. Mayo, larger defects required s. Chorvath. Utilization of
      corium grafts from resected skin requires to include the removal of epiderma and
      subcutaneous fat, and suture under traction. On the basis of the presented
      results, the authors recommend this type of repair of abdominal wall defects.

PMID- 7812826
TI  - [Endothelium and reactive forms of oxygen].
AB  - Recent experimental findings suggest that we should now consider some diseases as
      "endotheliopathies" and some others as "ROS-pathies". The presented review
      summarizes our knowledge on the role of endothelium and reactive oxygen species
      (ROS) in physiological processes and diseases. The vascular endothelium provides
      vital and responsive infrastructure of vessels for the circulation of blood and
      homeostasis of all organs. Due to its exposure to mechanical, chemical and
      biological factors, including ROS and the nature of its responses to these
      insults, it is involved in a wide variety of disease processes. Oxidative stress
      occurs also in many human diseases. Our understanding of the role played by the
      endothelium and ROS in disease pathology are still insufficient. To determine if
      endothelial and ROS-induced changes in hypertension, atherosclerosis,
      ischemia/reperfusion etc. are the primary cause of specific diseases or merely
      secondary effects remains to be clarified in several areas from inflammatory
      processes to cardiovascular diseases. Protection of the endothelium and
      antioxidant therapy represents a potential successful therapeutic approach in
      different diseases. In the near future the endothelial and free radical research
      will surely clarify many of our still unanswered questions.

PMID- 7812827
TI  - [Carcinoma of the breast during pregnancy and lactation].
AB  - The authors describe two patients with breast cancer which was manifested during
      pregnancy. The authors deal with diagnostic and therapeutic possibilities,
      depending on the stage of disease and the stage of the pregnancy. A delay of the
      diagnosis and adjuvant therapy deteriorates the prognosis of this disease.

PMID- 7812828
TI  - [Renal oncocytoma and its morphology, diagnosis and therapy].
AB  - Oncocytoma includes 3-5% of all renal tumors. It does not manifest itself by
      typical symptoms and often is diagnostically confirmed in coincidence with
      examinations of other diseases. The preoperative diagnosis of oncocytoma is
      difficult. Oncocytoma must be taken into consideration in cases of bilateral
      multilocular tumors of the kidney. Neither RTG, USG and CT examinations, nor
      angiography give the specific picture of oncocytoma. One of the possibilities of
      diagnosis confirmation is the peroperative biopsy. If the latter confirms the
      diagnosis, then according to possibilities, operation with maintenance of
      unimpaired renal parenchyme should be performed. The prognosis of the disease is
      good and depends on the stage of cellular differentiation of tumor. The study
      presents observations of 4 patients subdued to surgery at the Urologic Clinic
      FHwP in Kosice since 1981 to 1990. The patients survive without metastases for 3
      4 years.

PMID- 7812829
TI  - [NK cell activity and inhibition by anti-HLA monoclonal antibodies].
AB  - The authors followed the effect of anti-HLA class I and II monoclonal antibodies
      on cytotoxic activity of human NK cells. The mAb 18/5, 23/9 and beta 2m (anti-HLA
      class I) as well as mAb 20/DR, 30/DR, 13/DP and FB6/DP (anti-HLA class II) were
      used. Both groups of the antibodies were either tested directly during the
      cytotoxic test, or NK cells were pre-incubated with them. The application of the
      antibodies results in an inhibition of NK cell activity by the average of one
      third. However, the pre-incubation of NK cells with the mAb has not been so
      unambiguous. On the other hand, the application of anti-HLA class I and class II
      mAb had no effect on the interaction of NK cells with their target cells. We can
      conclude that HLA molecules might play a role in the late stages of the cytolytic
      mechanism of NK cells. (Fig. 1, Tab. 2, Ref. 21.)

PMID- 7812830
TI  - [Ethical principles in working with live animals and human fetal tissue in
      biomedical research].
AB  - The regulations for the protection of experimental animals which are suggested
      are based on internationally recognized ethical principles. The research
      institutions should establish and maintain appropriate policies and procedures to
      ensure the human care and use of live vertebrate animals. Recent developments in
      the use of human fetal tissue for therapeutical transplantations represent some
      serious ethical problems. Proposals for the ethical use of human fetal tissues
      are suggested. (Ref. 8).

PMID- 7812831
TI  - [Invasive cardiology in a heart transplantation program].
AB  - The heart transplantation is a clinical therapeutic method which significantly
      improves quality and longevity in some of the patients with severe and otherwise
      uncorrectable heart failure. Success of the procedure depends on highly organized
      and multidisciplinary medical cooperation. The paper presents an overview of the
      main cardiological invasive techniques and their role in heart transplantation
      programme. The presented analysis is based in more than 10 years of the author's
      own experience with heart transplantation in clinical medicine and on critical
      analysis of the current publications on this topic. (Tab. 4, Fig. 7, Ref. 53.)

PMID- 7812832
TI  - The role of pineal gland in circadian rhythms regulation.
AB  - In the presented article we try to find a synthesis of the current knowledge on
      circadian rhythms. We pick up the most prominent oscillations in human physiology
      and review the current knowledge of their regulation. Circadian oscillations in
      the parameters of internal environment are driven by the pineal gland. A
      biochemical pathway in the pineal transforms tryptophan through serotonin to the
      final product--the indolamine melatonin. Its plasma level is high at night and
      low during the day. Melatonin, easily penetrating through biological barriers,
      thus carries phase of day information to all peripheral tissues. Light exposure
      of retina alters (via neural pathways connecting retina to pineal gland) the
      amount of serotonin metabolized to melatonin. This physiological mechanism of
      adjustment of the endogenous clock to the solar day can be altered in some
      circumstances, leading to pathologic symptoms. The best known diseases caused by
      breakdown in circadian regulation are seasonal affective disorders and jet-lag
      syndrome. (Fig. 2, Ref. 71.)

PMID- 7812833
TI  - [Pathogenesis, prevention and detection of cardiotoxicity of anthracycline
      cytostatic agents].
AB  - BACKGROUND: Anthracycline antibiotics represent a part of therapeutic schemes in
      the treatment of a wide spectrum of malignancies. Precisely due to their
      cytostatic effectiveness they are being applied in spite of the risk of cardiac
      damage of patients. Anthracycline cardiotoxicity may culminate in potentially
      irreversible heart failure and fatal arrhythmias. Consequences of cardiotoxicity
      can complicate and shorten the lives of patients with formerly favourable
      prognosis of the malignant disease, and even of those that have been cured.
      OBJECTIVES: The aim of the presented study was to provide a review on current
      opinions concerning the pathophysiological mechanisms of cardiotoxicity due to
      anthracycline antibiotics, as well as the possibilities of cardiotoxicity
      prevention and detection. The procedure of cardiac monitoring of anthracycline
      effects is performed in order to detect the initial stage of myocardial
      impairment which is on the level of microstructural alterations. This requirement
      is mostly fulfilled by the invasive method of endomyocardial biopsy. Also the
      noninvasive method of high-resolution electrocardiography may reflect anatomic
      electrophysiological abnormalities on the level of cardiomyocytes and
      interstitium. We decided to verify the usefulness of this method in the sense of
      the ability to detect the risk of the cardiotoxicity origin following
      anthracycline application. METHODS: We have repeatedly observed 34 hospitalized
      patients with cancer before or during chemotherapy. On the basis of high
      resolution electrocardiography we have analysed the ECG signal in regard to time,
      frequency and time-frequency relation. RESULTS: In this study we present our
      initial experience with this method in combination with electrocardiographic and
      echocardiographic findings. In regard to the fact that the observations were of
      short term character we interpret our results of high-resolution
      electrocardiography as being preliminary. We report 4 illustrative cases of
      patients who independent of the dosage, yielded distinct responses toward the
      applied potentially cardiotoxic therapy. CONCLUSIONS: We consider the high
      resolution electrocardiography in regard to its noninvasive character and low
      demand of time and finance to represent a perspective method of cardiac
      monitoring of the negative anthracycline effect. Not only ours but also the first
      experience in the world confirm this presupposition. By means of this method we
      have been able to detect initial alterations due to already low cumulative doses
      of anthracyclines (120 mg/m2 in a patient with ischemic heart disease and 260
      mg/m2 in a patient with unimpaired myocardium prior to treatment). Our results
      also confirm the fact that the problem of cardiotoxicity must be necessarily
      strictly individualized. (Fig. 19, Ref. 80.)

PMID- 7812834
TI  - [NK cell activity and association with the HLA class I antigen complex].
AB  - To contribute to the genetic regulation of NK cell cytotoxic activity an
      association between HLA antigens and a level of cytolysis of target cells (K-562)
      have been followed. By investigating of NK cell cytotoxic activity in 183 HLA
      typed healthy persons it was found that high levels of cytolytic function of NK
      cells were associated with the antigens of HLA-B8, HLA-B27, HLA-B40, and HLA-B44
      as well as the HLA-A2,-B12 phenotypes (in male only). It was also found that low
      NK cell cytotoxic activity was significantly correlated with homozygosity at HLA
      loci. These results suggest that HLA genes or genes linked with them may control
      NK cell cytotoxic functions in man. The authors have also suggested that above
      mentioned HLA-B antigens might belong to the activating receptor family of NK
      cells. (Tab. 7, Ref. 48.)

PMID- 7812835
TI  - Development of brown adipose tissue in the rat and thyroxine administration
      influence.
AB  - The role of the thyroid hormone in the activity of brown adipose tissue (BAT) is
      in most papers underestimated and it is the noradrenaline which is considered as
      the main regulator. The aim of the presented experiments was the study of the
      effect of 2 or 3 administrations of thyroxine (T4) applied to young rats of
      different age on the weight of BAT. T4 was injected in relatively large doses,
      i.e. 1 microgram/gram BW/day dissolved in 0.005 mmol NaOH intraperitoneally.
      Changes in T4 injected animals were compared with their litter-mate control,
      which were injected with solvents. In control animals the relative weight in
      mg/100 g BW was significantly higher during the entire first postnatal month in
      comparison with adult animals. Three administrations of T4 caused significant
      increase in relative as well as in absolute weight in all age groups. The
      difference was significant in dry tissue also. When the change was expressed in
      percentage the greatest effect of T4 was found in 15- and 19-day-old animals.
      Another experiment followed the effect of only two injections of T4 on BAT to
      animals of 7 different litters but of the same age, i.e. on day 5 and 6 and
      euthanized as 7-day-old. In all litters the increase after T4 treatment was
      significant; the increase in % ranged from 20 to 40% and was influenced by the
      level in controls. The relative weight in control animals ranged from 620 to 920
      mg/100 g BW. This between-litter variance is greater than the effect of
      T4.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7812836
TI  - [Lipid and pro-oxidative and antioxidative parameters in the blood of
      vegetarians].
AB  - The authors subdued 183 vegetarians to examination, the aim of which was to judge
      the state of health and nutrition of the vegetarian population. The examined
      group was composed of people with their age ranging from 19-60 years, out of
      which 102 were of younger (19-39 years) and 81 were of older age. Their average
      period of vegetarian food consumption was 4.2 years. One third of men and a half
      of women were lacto-vegetarians, the rest were lacto-ovo-vegetarians. The results
      were compared with 160 nonvegetarians (64 of younger and 96 of older age). The
      detected values of lipid parameters were evaluated as favourable for vegetarians
      (low values of cholesterol, triacylglycerols, atherogenic index, LDL-cholesterol,
      the share of HDL-cholesterol was 28-33% (vs 24-26% in nonvegetarians) with values
      converging to 1.4 mmol.l-1--i.e. reduced risk). Additional favourable factors in
      prevention of atherosclerosis include the absence of obesity in vegetarians and
      values of antisclerotic active substances in blood (high values of vitamin C, in
      comparison with nonvegetarians a significantly higher molar ratio of vitamin
      E/cholesterol and vitamin E/triacylglycerols--more effective protection against
      peroxidation of lipids). Vegetarian mode of food consumption may be favourably
      evaluated regarding prooxidative-antioxidative parameters which play an important
      role in the process of atherogenesis, and carcinogenesis. Significantly lower
      values of conjugated dienes in plasma of vegetarians and vice versa high values
      of antioxidant substances (vitamin C, vitamin E/lipid components, catalase
      activity) were detected. A more pronounced system of detoxication in vegetarians
      is important due to a possible risk of an increased intake of xenogenous
      substances. (Tab. 3, Ref. 27.)

PMID- 7812837
TI  - [Does selectivity in radical adenomectomy in invasive hypophyseal adenomas
      increase the risk of recurrence?].
AB  - Between 1989 and 1992 we operated 52 patients primarily due to pituitary adenoma.
      The tumor growths were evaluated microsurgically or histologically as invasive in
      29 of them. Radical adenomectomy was achieved in 65.5% of patients with invasive
      and in 91.3% of patients with noninvasive pituitary adenoma--in 40 cases
      altogether. Although it was possible to identify and preserve pituitary tissue
      remnants in 23 cases, the real selectivity, confirmed by biochemical testing, was
      finally achieved only in 16 of them. Only one recurrence, 8 months after the
      radical nonselective removal of nonfunctional extrasellar invasive adenoma
      occurred during the median follow-up time of 2.61 years (minimal follow-up time 1
      year). We have found out no significant differences in the recurrence rates
      between invasive and noninvasive pituitary adenomas after their radical selective
      and nonselective removal. We suppose that nonselective radical adenomectomy is
      not necessary to prevent the recurrence of the invasive pituitary adenoma. (Tab.
      7, Ref. 15.)

PMID- 7812838
TI  - [Prenatal cytogenetic diagnosis of trisomy 21 using amniotic fluid cells].
AB  - BACKGROUND: Trisomy 21 is the most frequent chromosomal disorder which is
      associated with advanced maternal age. OBJECTIVES: The aim of our work was to
      examine the risk of trisomy 21 occurrence in a group of pregnant women subdued to
      prenatal cytogenetic examination. METHODS: The examined group consisted of 1128
      pregnant women. The cells for cytogenetic analysis were obtained by means of
      transabdominal amniocentesis during the second trimester of pregnancy.
      Cultivation of amniocytes lasted 15-20 days. The chromosomes were stained by a
      conventional and G-striping method. RESULTS: Cytogenetic analyses have indicated
      that the aberrant karyotype was present in 32 (2.82%) out of 1128 fetuses. In
      addition the results have confirmed that trisomy represented the most frequent
      chromosomal aberration (60%) detected by means of prenatal cytogenetic diagnostic
      examinations and the risk of its incidence increased exponentially in women who
      were older than 35 years of age. CONCLUSIONS: The prenatal cytogenetic diagnosis
      represents a significant role in the prevention of hereditary conditioned
      chromosomal disorders. (Tab. 1, Fig. 1, Ref, 13.)

PMID- 7812839
TI  - [Non-invasive study of cardiovascular function using models of biological age].
AB  - In a group of 67 healthy persons (18-60 yrs, mean 37 yrs, male 32, female 35) 77
      parameters were investigated (9 physical, 6 biochemical, 3 from ECG, 14
      polygraphic, 45 echocardiographic), in 38, ones a significant correlation
      (Pearson's) with age was found. Biological age or functional cardiovas. age (BA),
      was calculated using the following formulas: 1.BA = .23BMI- +.11mBP-.43PTT
      +29.58CO/LVET-.4vPWT-.16FS +15.27h/r, r = 0.980. 2.BA1 = .22mBP +.8AoR-.4vPWT
      .19FS +.04iMLV, r = 0.968. BMI--body mass index, mBP--mean blood pressure in
      Torr, PTT--pulse transmission time (CARi-AII in FCG) in ms, CO/LVET--duration
      between C-O points in apexcardiogram in ms/left ventricular ejection time (CARu
      CARi in carotidogram) in ms ratio, vPWT--velocity of posterior wall thickness of
      left ventricle in mm.s-1, FS--fractional shortening in %, h/r--2(enddiastolic
      posterior wall thickness of left ventricle in mm)/enddiastolic diameter of left
      ventricle in mm ratio, AoR--diameter of the aortic root (mm), iMVL--index of
      massa of the left ventricle. No significant correlation between heart rate and
      tests using in formula was found. We found "normal biological age" or
      cardiovascular function in all groups. But the significant differences between
      men and women in relative biological age (ca 12% using formula 1, 19% using
      formula 2, both p < 0.001) were found. (Tab. 3, Ref. 23.)

PMID- 7812840
TI  - [The antitussive effect of theophylline].
AB  - Theophylline belongs to a group of medicaments used in asthma therapy. It yields
      an antiinflammatory effect, reduces allergic reactions, and in respiratory
      airways it improves the mucociliary clearance and eminently dilates smooth
      muscles. Therefore, the main aim of our interest is its effect on the cough
      reflex. Cough was evoked by mechanical irritation of the airways in cats with
      chronic tracheal cannula. It has been discovered that theophylline, when dosed 10
      mg per kg of body weight i.p. achieved a more intensive effect than
      dextromethorphane, namely in evaluation of cough parameters, but it had a lower
      suppressive effect than codeine. (Fig. 3, Ref. 13.)

PMID- 7812841
TI  - [Retrorectal and presacral tumors].
AB  - The group of patients with retrorectal and presacral tumours is presented. Their
      clinical picture, CT examination, results of biopsy and surgery treatment are
      analysed. The authors present the recent procedures of diagnosis and therapy of
      tumors in this location.

PMID- 7812842
TI  - [Psychosomatic diseases in dermatology].
AB  - The presented work provides a review of literature dealing with dermatoses
      (dermatitis atopica, eczemas, allergies, urticaria, pruritus, etc.) from the
      psychosomatic point of view. The presented work attracts attention to the
      association of psychical state with the skin; it indicates the necessity to
      comprehend each patient from the bio-psycho-social aspect and to take into
      account the multifactorial etiopathogenesis of each disease. The author
      recommends cooperation between dermatologists, clinical psychologists and
      psychiatrists. The aim of the cooperation is to supplement local therapy by
      psychotherapy in psychosomatic disorders, and the field of psychodermatology by
      psychopharmacology.

PMID- 7812843
TI  - [New findings on cardiomyopathies].
AB  - In this review the authors summarize the newest knowledge on cardiomyopathies,
      which was obtained during the last ten years due to joint experimental and
      clinical in this field. It concerns the pathogenesis of cardiomyopathies from the
      point of view of metabolic damage of the heart on the cellular and subcellular
      level, the diagnosis--mainly by means of echocardiographic investigation, as well
      as the therapy of cardiomyopathies--medicamental and surgical (transplantation of
      the heart). (Ref. 6.)

PMID- 7812844
TI  - [Significance of mitochondrial Ca2+ transport in ischemic injury and myocardial
      protection].
AB  - The role of calcium regarding the origin of irreversible impairment of the
      myocardial tissue is being intensively studied. An important role in this process
      is played by mitochondria which by means of the active Ca2+ uptake stimulate its
      oxidative metabolism and intervene into the Ca2+ homeostasis in mitochondrial
      cells. The study investigates the influence of cardioprotective substances with
      distinct mechanisms of the mitochondrial Ca2+ uptake effect. The experiments were
      performed on chinchilla buck rabbits of 2500-3000 g of body weight. Isolated
      hearts were perfused according to the method of Langendorff, ischemia was evoked
      by a 60-minute stoppage of the coronary blood flow. The cardioprotective
      substances were added into the perfusion solution prior to ischemia inducement.
      We investigated the following cardioprotective substances: Spirapril (ACE
      inhibitor), magnesium (Mg2+), and MDL 73,404 (antioxidant, synthetic analogue of
      alpha-tocopherol). After the 60-minute ischemy the mitochondrial Ca2+ uptake
      decreased by 43% in comparison with the control group (p < 0.01), Spirapril
      caused its accretion by 35% in comparison with the ischemic group (p < 0.05), and
      magnesium increased the uptake even by 52% (p < 0.001). The MDL 73,404 substance
      had no effect on the mitochondrial Ca2+ uptake. On the basis of experimental
      results we assume that the cardioprotective effects of Spirapril and magnesium
      can be besides other factors intermediated also by the increase of
      intramitochondrial enzymatic activity in consequence of augmented transport of
      Ca2+ into mitochondria. The cardioprotective effect of the MDL 73,404 substance
      is assumedly caused by its antioxidant properties. (Fig. 4, Ref. 21.)

PMID- 7812845
TI  - [The galactose eliminating capacity of the liver and its protein synthesis
      function in chronic liver diseases].
AB  - Assessment of the galactose elimination capacity has appeared to represent an
      suitable index of the total metabolic capacity of the liver inflicted with
      chronic hepatopathy. In a more severe disease e.g. cirrhosis hepatis the GEC
      assessment enabled to judge appropriately the among of hepatic tissue reduction
      which does not necessarily have to correspond with the grade according to Child
      Pugh classification. It represents an helpful criterion also for a smaller
      decrease of the functional capacity of the liver, e.g. in moderate forms of
      hepatopathies, as e.g. steatosis and steatofibrosis hepatis, chronic active
      hepatitis. By means of examinations of the hepatic proteosynthetic function
      indices it was discovered that the level of prealbumin and the activity of
      cholinesterase are more sensitive parameters of the functional ability of
      impaired liver in comparison with albumin, prothrombin complex and transferrin.
      Assessment of prealbumin and cholinesterase in the group of patients with
      cirrhosis hepatis enabled the most significant mutual distinction of differently
      severe grades, in three differing subgroups of cirrhotic patients (Ci A, Ci B and
      Ci C). The presented parameters were significantly distinct also in groups of
      patients with chronic active hepatitis, and steatosis and steatofibrosis of the
      liver. (Fig. 6, Tab. 1, Ref. 29.)

PMID- 7812846
TI  - [Oxidative phosphorylation in liver mitochondria after injury with carbon
      tetrachloride and during regeneration].
AB  - The study investigates the effect of a singular dose of CCl4 (2.5 ml/kg) on the
      concentration of triacylglycerols in the liver and oxidative phosphorylation in
      hepatic mitochondria after 24, 72 hours, 2 and 4 weeks since CCl4 application. It
      was discovered that 24 and 72 hours after CCl4 application the concentration of
      triacylglycerols increased significantly and steatosis of the liver supervened.
      After 2 and 4 weeks the triacylglycerol concentration values reached the level of
      those of control. The hepatic steatosis disappeared. The indices of oxidative
      phosphorylation index of respiration control, oxygen consumption during
      stimulated respiration (state 3), oxygen consumption during basal respiration
      (state 4), and phosphorylation velocity decreased significantly after 24 and 72
      hours after CCl4 application in all observed substrates--glutamate, pyruvate and
      jantarane. After 2 to 4 weeks the observed indices reached the level of values
      characteristic for healthy controls. The results have indicated that after the
      CCl4 toxic impairment the energy metabolism in hepatic mitochondria has been
      significantly impaired. This impairment, in spite of its severeness, was
      irreversible and hepatocytes were able to compensate it (Tab. 4, Ref. 33).

PMID- 7812847
TI  - [Prevention of progression in nephropathies].
AB  - Intermittent dialysis is excessively expensive and pretentious psychologically
      and socially. As a result the research is concentrated on the prevention of
      kidney disease progression. Preventive measures: a) Protein restriction forms the
      basis of nonpharmacologic measures. b) Consequent antihypertensive therapy, with
      the aim to decrease blood pressure < 17.5/11.25 kPa (140/90 Torr), is the most
      effective prevention. The basic drugs are ACEI eventually in combination with Ca
      antagonists. They even reverse kidney disease progression in early phases. c)
      Antiaggregation therapy prevents the formation of fibrin deposits in glomeruli
      and the thrombogenesis. d) Insulin resistance correction prevents the development
      of glomerulosclerosis and atherosclerosis. e) Antihyperlipemic therapy is
      required only in a small number of patients. f) Correction of mineral balance
      prevents or corrects osteodystrophy. These measures could decrease kidney disease
      progression and the entrance of patients into intermittent dialysis by 10-20% and
      a further decrease to 50% is expected to be reached until the year 2000. (Fig. 3,
      Tab. 3, Ref. 43.).

PMID- 7812848
TI  - [Insulin resistance: its clinical importance and trends in modern research].
AB  - Insulin resistance is the major pathogenetic link of atherosclerosis development
      and progression. The clinical diagnosis is made on the basis of analysis of
      glycemic and insulinemic response during the oral glucose tolerance test. Insulin
      resistance prevalence is constant in NIDDM and advanced renal failure, and almost
      50% in early stages of essential hypertension and kidney diseases. Its prevention
      and therapy are effective. The increase of free Ca and decrease of free Mg
      concentrations participate both in insulin resistance and hemodynamic changes in
      diseases of the Reaven's syndrome. The intracellular mineral dysbalance is caused
      by the alteration of Na+,H(+)-antiporter. (Fig. 1, Tab. 4, Ref. 51.).

PMID- 7812849
TI  - [Endoscopic therapy of biliary tract diseases].
AB  - Endoscopy plays a dominant role in the diagnosis and treatment of biliary tract
      disease and disease of pancreas as well. The authors of the article present their
      own experience with the endoscopic treatment of these diseases which they have
      obtained since 1982 by performing endoscopic papilosphincterotomy in 2000
      patients (1340 female and 660 male patients). The most common indication for this
      treatment was choledocholithiasis and benign stenosis of Vater's papila (or
      dysfunction of Oddi's sphincter). They succeeded in 97.9%, the worst results were
      in patients after the B II-resection of the stomach. The occurrence of
      complications was 3.4% in the entire group of patients, mortality was 0.5%. In
      the next part of the article the authors present other methods of treatment of
      choledocholithiasis and other diseases of biliary a pancreatic duct system
      (extraction of biliary stones, lithotripsy, biliary and pancreatic drainage).
      According to the literary data and own experience the endoscopic treatment of
      biliary diseases is highly effective and relatively safe when performed by
      experienced specialists. (Tab. 2, Ref. 16.)

PMID- 7812850
TI  - [Colonoscopy monitoring intervals after polypectomy of adenomas of the large
      intestine in patients younger than 40 years of age].
AB  - A group of patients younger than 40 years of age, who had been subdued to
      endoscopic large intestine adenoma polypectomy were compared with the rest of the
      patients regarding the adenoma occurrence according to sex, localisation,
      histologic character, frequency of recurrence, and carcinoma formation in the
      large intestine in the site of previous polypectomy. The compared groups of
      patients differed merely in time of recurrence. In patients over 40 years of age
      the adenomas reoccurred most frequently in the first and fifth years following
      the primary polypectomy. In patients after primary polypectomy regular
      colonoscopic controls were suggested, namely after the first year and
      subsequently after every two years. This scheme is appropriate also for patients
      under the age of 40 years. Therefore the recommended intervals of colonoscopic
      controls at this age category do not require to be subdued to alteration. (Tab.
      14, Ref. 5.)

PMID- 7812851
TI  - [Interaction of cholesterol and sphingomyelins in membranes of the sarcotubular
      system after denervation].
AB  - We investigated the content of cholesterol and phospholipids in the sarcotubular
      membranes from the rabbit fast-twitch muscle in various time intervals after the
      section of sciatic nerve. Along with the unchanged content of total phospholipids
      we found an increase of cholesterol in all investigated intervals. Significant
      elevation of cholesterol by about 33.8% following 14 days of denervation is
      associated with a three-times higher level of sphingomyelins. The elevated level
      of sphingomyelins persists after 28 days and the molar ratio
      cholesterol/phospholipids is 2.6 times higher in comparison with the control
      group. Investigation of cholesterol synthesis on muscle slices from the precursor
      14C-mevalonic acid as well as of the activity of HMG-CoA reductase have shown
      that the cholesterol increase following denervation is not in correlation with
      its synthesis de novo. Similarly it has been shown that an increase of membrane
      cholesterol is not linked with the change of membrane fluidity (Tab. 3, Fig. 3,
      Ref. 30.)

PMID- 7812852
TI  - [High frequency ventilation in the newborn infant].

PMID- 7812853
TI  - [Ventilation by high frequency oscillations in adults. An experimental study of
      conditions and methods].
AB  - A hydraulic pump with an adjustable stroke delivering up to 145 ml at 1 to 45 Hz
      has been used to ventilate adult pigs of a weight between 60 and 140 kg. After
      tracheotomy the curarized animals were connected to the pump by a metallic tube
      through which a bias flow was directed. This flow (FiO2 0.35) was humidified by a
      special ceramic device and aspirated at the distal end of the tube. It was
      demonstrated that under these conditions gaz exchange was well maintained with
      oscillations between 15 and 35 Hz. Higher frequencies were needed for the heavier
      animals. Blood gas measurements of samples from segmental pulmonary veins
      demonstrated regional differences in gas exchange. These could be modified by
      adjusting the oscillation frequency. Reinhalation of gas could be prevented by an
      increase of the bias flow. Alveolar recruitment by initial pulmonary inflation by
      a pressure of 18 +/- 2 cm H2O is required for adequate oxygenation. Maintenance
      of adequate elimination of CO2 required a bias flow of 35 +/- 5 l/min. Mean
      pressure in the airways was maintained at 12 +/- 1 cm H2O. This pressure
      determines the value of PaO2. Ordinary endotracheal tubes tend to collapse during
      the sucking phase of the pressure cycle. Rigid or armed tubes are required. They
      must allow for aspiration of the bias flow from the distal end of the tube.

PMID- 7812854
TI  - [Results of high frequency ventilation in the very low birth weight premature
      infant].
AB  - High frequency ventilation (HFV) has been used by the authors for about 5 years
      in low-weight premature neonates with severe hyaline membrane disease. This
      retrospective study concerns principally three classes of results: 1) early
      results of HFV vs conventional ventilation; 2) middle term results, HFV having
      been used in most severe cases; 3) long term outcome: HFV might prevent
      efficiently delayed complications such as bronchotracheal dysplasia. Recent
      therapy developments (surfactant, new ventilators) require controlled prospective
      studies to assess the real benefits of HFV compared with conventional methods.

PMID- 7812856
TI  - [High frequency oscillation ventilation after surfactant use in hyaline membrane
      disease. Outcome of ventilation parameters].
AB  - Surfactant therapy in hyaline membrane disease (HMD) does not suppress all risks
      of subsequent broncho-pulmonary dysplasia. This study aimed to estimate the
      efficacy of Surfexo followed by high frequency ventilation (HFV) on respiratory
      parameters and long term outcome. 47 neonates (44 premature) with HMD received
      first Surfexo then HFV whenever hypercarbia (pH < 7.25, PaCO2 > 7 kPa) and/or
      hypoxaemia (PaO2 < 7kPa, FiO2 = 0.5) continued. Surfactant was given at 3 hours
      of life (mean), HFV was started at 5 h (mean) and continued for 36 h (mean). FiO2
      was lowered after a HFV of 3 h (p < 0.01) and mean broncho-tracheal pressure
      decreased after 12 h (p < 0.001). Six children deceased (1 from massive pulmonary
      haemorrhage, 5 from neurological complications), 1 developed pneumothorax (this
      was the only barotraumatic complication in our series), 2 children had a mild
      broncho-pulmonary dysplasia. All the 38 remaining patients had a good
      uncomplicated outcome. Thus Surfexo -HFV association appears to be an excellent
      therapy of HMD in newborns.

PMID- 7812855
TI  - [Persistence of fetal circulation and high frequency oscillation].
AB  - High frequency ventilation (HVF) was used in 17 newborns with severe respiratory
      distress due to persistent fetal circulation. All patients except one had been
      treated previously but not satisfactorily by conventional ventilation. Four
      children died from neurological causes despite respiratory improvement. HVF
      failed in one case. Twelve newborns recovered without any sequelae. Thus HVF
      appears to be a most valuable ventilation technique in this situation.

PMID- 7812857
TI  - [High frequency ventilation in neonatal surgery].
AB  - High frequency oscillatory ventilation (HFOV) is one of the artificial
      ventilation techniques used for the treatment of severe respiratory distress in
      the neonatal period. We studied (between 1987 and 1992) 57 newborn infants
      ventilated by HFOV during surgery. The aim was to facilitate the surgical
      procedure without having any deleterious effects on the gas exchange or the
      hemodynamic state of the infant. Three groups were studied. Group I (thoracic
      procedures: oesophageal atresia and pulmonary malformations, n = 25), group II
      (diaphragmatic hernia, n = 22), group III (abdominal procedures, n = 10). In the
      thoracic surgery group, no deleterious effect related to the HFOV was reported.
      The hyperventilation noticed after anaesthetic induction was rapidly corrected by
      placing the patient in a lateral position. In the three groups, no intraoperative
      complications related to the HFOV were observed. The diaphragmatic hernia group
      was divided into two subgroups according to the timing of surgery (emergency
      surgery, surgery after stabilization). In the latter subgroup, surgery was
      performed when the ventilation and gas exchange conditions had significantly
      improved. This subgroup showed the highest survival rate. This technique of
      peroperative ventilation is specifically used in the thoracic and diaphragmatic
      procedures of term and preterm newborn infants. It achieves a more stable
      operative field with less pulmonary expansions and diaphragmatic movements. In
      spite of the fact that HFOV is seldom used during anaesthesia, this study
      confirms its safety as well as the simplicity of its monitoring.

PMID- 7812858
TI  - [Congenital diaphragmatic hernia: results of the association of preoperative
      stabilization and oscillation ventilation. (A prospective study of 17 patients)].
AB  - The authors studied the efficacy of ventilation by high frequency oscillation in
      preoperative stabilization of 17 newborns with diaphragmatic hernia. This
      prospective study covered the pre-, intra- and postoperative periods. The
      preparation to surgery lasted 57 +/- 52 hr. The newborns were operated at 61 +/-
      46 hr of life and the duration of postoperative mechanical ventilation was 184 +/
      200 hours. Two groups were differentiated retrospectively. The first group (n =
      11) comprises neonates in whom a good preoperative stabilization was obtained and
      who underwent surgery before 48 hours. In this group all children survived at one
      month of life (one infant died at six months from cardiac malformation during
      heart surgery). The second group (n = 6) consists of neonates having required a
      longer time for stabilization. The operation was performed on the fifth day only.
      After one month, 5 children survived (one newborn died from intractable
      hypoxaemia at 5 days of life, surgical cure being impossible; 3 infants died
      belatedly from associated severe malformations). Predictive factors can be
      individualized: arteriolar-alveolar ratio, associated abnormalities and
      particularly these concerning heart, oxygenation index at birth, time required to
      stabilize the newborn condition. Nevertheless, the association of preoperative
      stabilization and ventilation by high frequency oscillation appears to improve
      the prognosis of congenital diaphragmatic hernia.

PMID- 7812859
TI  - [Postoperative analgesia for ambulatory surgery in children: a comparison of 2
      techniques].
AB  - In 40 children scheduled for circumcision, we studied the quality and the adverse
      effects of postoperative analgesia induced by caudal block (group 1) or
      acetaminophen by rectal route (group 2). Study lasted the six first postoperative
      hours. In recovery room, analgesia was more effective in group 1. Need of
      analgesic drugs was also lesser in group 1. Incidence of adverse effects was the
      same in the two groups.

PMID- 7812860
TI  - [Outcome of transfusion practices in general hospitals in Lorraine].
AB  - Authors carried out, in 17 public (non university) hospitals, a retrospective
      study on evolution of blood transfusion techniques in a french province
      (Lorraine). In every hospital, they obtained the annual consumption of blood or
      derivatives prescribed by the anaesthetists. Use of different sparing techniques
      was noted. All these parameters were connected to the anaesthetic and surgical
      activities. For statistical study, a Student test was used. Results demonstrate
      increasing anaesthetic and surgical activities. However the reduction of mean
      consumption of plasma and red blood cells is not significant. The sparing
      techniques are not fully used, partly because of too long distances from the
      blood centres. Blood prescriptions should and could be optimized.

PMID- 7812861
TI  - [Is hemodilution sufficient to avoid homologous blood transfusion in reduction
      mammaplasties?].
AB  - The unpredictability of blood loss during reductive mammoplasties induced the
      authors to use a blood-sparing technique so as to avoid homologous transfusions.
      Intentional isovolaemic haemodilution (IIH) was performed in 38 patients.
      Clinical and biological criteria were used for analyzing the results. In this
      prospective study, IIH could not prevent the necessity of homologous transfusion
      for 3 patients, in the early postoperative period. In one of these cases,
      clotting of blood prevented its utilization. Therefore IIH appears to be an
      interesting alternative blood-sparing method in patients who cannot benefit
      easily from preoperative programmed blood auto-donation.

PMID- 7812862
TI  - [Residual infectious risk of blood transfusion].

PMID- 7812863
TI  - [Transfusion security].

PMID- 7812864
TI  - [Hemosurveillance. A device for transfusion medicine].

PMID- 7812865
TI  - [Erythrocyte concentrates].
AB  - Among the blood products distributed by blood banks red cell concentrates are
      mostly prescribed, for treating anaemia. We now have a relatively large choice of
      specially prepared red cell concentrates, which enables us to satisfy more
      accurately each patient's particular requirements. In order to select the best
      suited and safest product, the risk associated with the patient's disease as well
      as the side effects of red cell transfusion should be evaluated.

PMID- 7812867
TI  - [Indications of the different components of blood and outcome of transfusion
      practices in postpartum hemorrhage].
AB  - Despite a high incidence of mortality associated with post-partum haemorrhage,
      indications for transfusion of blood and its components in obstetrics remain ill
      defined. Transfusion is often massive if needed. Transfusion management depends
      upon appreciation of blood loss, with systematic research of associated
      disseminated intravascular coagulopathy (DIC) or other preexisting coagulation
      disorders. If DIC is ruled out, the classic rules of volemic substitution apply,
      besides certain qualitative characteristics intrinsic to the blood components or
      products used. Treatment of DIC calls for fresh frozen safely screened plasma,
      fibrinogen or platelets concentrates. Indications for autologous transfusion are
      very limited in these circumstances.

PMID- 7812866
TI  - [From the transfusion informationcard to the tracing of blood products].
AB  - The transfusion sheet established in 1985 with the aim of improving the
      immunological safety has not fulfilled the goal expected. Furthermore, it is now
      clear that the immunological safety does not necessarily imply transfusional
      safety only, though alertness in this field should be maintained. The residual
      post transfusional risk, though limited, should remain a permanent concern both
      for the transfuser and the prescriptor. "Haemovigilance" has become an integral
      part of the transfusional safety. It cannot exist without a trace-back of the
      blood products. At any time it should be possible to determine: "who received
      what and from whom?" The blood bank has the responsibility for the link between
      the donor and the blood product and the clinician has the responsibility of the
      link between the blood product and the recipient. Both partners must be aware of
      the absolute necessity of sharing and checking all information. Means for this
      trace-back exist, sophisticated or not, and more or less costly. It is up to each
      one to select the most suitable system.

PMID- 7812868
TI  - [Indications of blood components and outcome of transfusion practices in
      hemorrhage of multiple trauma].
AB  - Bleeding occurring in a patient with multiple trauma has an unpredictable
      evolution; blood losses are often very important and their origins mostly
      unclear. These problems should not prevent the use of a strategy for optimal use
      of blood components. Indications for packed red cells, fresh frozen plasma,
      platelets and coagulation factors are discussed. Indications for packed red cells
      are discussed in relation with the patient's conditions (myocardial, cerebral and
      pulmonary functions) and the clinical status. If the patient is shocked,
      transfusion must be ordered to maintain a haemoglobin level greater than 10 g.100
      ml-1. Considering its cost, the use of albumin must and can be reduced when fluid
      replacement is realized with long lasting colloids, like starch. Warming of
      transfused blood is necessary, especially if acceleration disposals are used to
      prevent or minimize hypothermia. Use of portable monitors for haemoglobin and
      coagulation parameters is recommended.

PMID- 7812869
TI  - [Locoregional anesthesia for non cardiac surgery in the cardiac patient].
AB  - Perioperative cardiovascular morbidity is a common challenge for the
      anaesthesiologist, who has daily to manage patients with coronary and/or cardiac
      insufficiency and/or arrhythmias. Regional anaesthesia (RA), especially epidural
      could reduce morbidity and mortality in the cardiac patient, but the topic
      remains controversial. The authors propose a review of the cardiovascular effects
      of RA and of various RA techniques that can be used in the cardiac patient.
      Finally, they discuss the choice of the anaesthetic technique according to the
      cardiac disease.

PMID- 7812870
TI  - [A pitfall for catheterization: the left superior vena cava].

PMID- 7812871
TI  - [Peranesthetic acute respiratory failure disclosed by prone position in a child
      with mediastinal adenopathy].

PMID- 7812872
TI  - [Hemosurveillance: ethical and medicoeconomic constraints].

PMID- 7812873
TI  - [Hemosurveillance: the physician's point of view].
AB  - Physicians are overloaded with the new Health Department rules about follow-up of
      transfused patients. Indications of fresh frozen plasma must be restricted and
      its use must be decreased; patients must be informed before and after transfusion
      and all informations about transfusion must be collected in a special file. This
      file will permit to answer the question: "Who received what?" Incidents occurring
      during transfusion need to be collected and transmitted to the "Centre National
      d'Hemovigilance". Such a policy will be effective only with an actual help (i.e.
      financial help) of the administration.

PMID- 7812874
TI  - [Angioplasties: is anesthesia necessary?].
AB  - Percutaneous transluminal angioplasty of lower limbs, renal, mesenteric, coronary
      or supra-aortic arteries is a technique in progress. Nevertheless patients
      concerned are high-risk patients who are always anxious about the angioplasty
      result. Ambulatory anaesthesia is required. Local anaesthesia of artery puncture
      site is effective. Low-osmolality contrast media should be chosen to reduce
      injection pain. Calcium blockers and molsidomine could prevent "arterial
      vasospasme". Finally, the major aim of anaesthesia is to limit patient's anxiety.
      In most cases orally premedication is enough. The presence of the
      anaesthesiologist during the procedure is not required but resuscitation devices
      must be available.

PMID- 7812875
TI  - [European transfusion practices: the SANGUIS survey].
AB  - The European study group, SANGUIS, tried to understand the transfusion behaviour
      of 158 teaching hospital surgical teams between october 1990 and september 1991.
      A partial series of 649 patients, from 20 teaching hospitals from 7 countries,
      having undergone a first elective total hip replacement is discussed. 15% were
      not transfused any blood at all. The number of patients transfused varied with
      the hospital, from 44% to 100%. Those patients transfused homologous blood only
      were exposed to a mean of 3 donors each. The teams who tended to transfuse more
      patients also tended to transfuse each of them with a greater number of blood
      units. There were great variations in each team in the use of blood products as
      well as blood derivatives and substitutes. Work must be done to obtain convergent
      practice by reviewing the indications for transfusion in elective surgery, and to
      increase the use of autotransfusion techniques.

PMID- 7812876
TI  - [Regional anesthesia in pediatric surgery. An Italian experience in the Gaslini
      Institute].

PMID- 7812877
TI  - [Techniques of security of plasma transfusion].
AB  - Viral inactivation of fresh frozen plasma (FFP) is the main condition of a safe
      administration in its few remaining indications. Different techniques have been
      developed such as "quarantine", solvent-detergent plasma treatment,
      pasteurization or, more recently, photosensitizing agents adjunction. None of
      these techniques is entirely satisfactory and further clinical studies are
      needed. Meanwhile, FFP use must be restricted to some well known congenital ou
      acquired pathologies where it cannot be substituted.

PMID- 7812878
TI  - [Management of high frequency oscillation ventilation in respiratory distress of
      the newborn infant].

PMID- 7812879
TI  - [Weaning of high frequency oscillation ventilation].

PMID- 7812880
TI  - [The first Anesthesia Society].

PMID- 7812881
TI  - The rising trend in allergic illness: which environmental factors are important?

PMID- 7812882
TI  - IL-4: a key cytokine in atopy.

PMID- 7812883
TI  - The role of alternative therapies in the treatment of allergic disease.

PMID- 7812884
TI  - Atopic sensitization and respiratory symptoms among Polish and Swedish school
      children.
AB  - Allergic sensitization and symptoms from the airways in relation to air pollution
      were compared in 10-12-year-old school children (n = 1113) from urban Konin in
      central Poland and both urban and rural parts of Sundsvall in northern Sweden.
      The measurements included parental questionnaires, skin-prick tests and serial
      peak flow measurements during 2 weeks with simultaneous monitoring of outdoor air
      pollutants. The skin-prick test technique was validated by IgE antibody
      determinations. The levels of common industrial pollutants, SO2 and smoke
      particles were much higher in Konin than in urban Sundsvall and the levels of NO2
      were similar. Various respiratory symptoms were more often reported among school
      children in Konin (except for wheezing and diagnosed asthma). Multiple logistic
      regression analyses yielded the following increased odds ratios for children in
      Konin as compared with the reference group (rural Sundsvall): chest tightness and
      breathlessness 3.48 (95% confidence interval 2.08-5.82), exercise-induced
      coughing attacks 3.69 (95% confidence interval 1.68-8.10), recurrent episodes of
      common cold 2.79 (95% confidence interval 1.53-5.09) and prolonged cough 4.89
      (95% confidence interval 2.59-9.23). In contrast, as compared with rural
      Sundsvall, the adjusted odds ratio for a positive skin-prick test was decreased
      in Konin, but increased in urban Sundsvall, 0.58 (95% confidence interval 0.37
      0.91) and 1.67 (95% confidence interval 1.15-2.42) respectively. The study
      confirms that living in urban, as compared with rural areas, is associated with
      an increased prevalence of respiratory symptoms and sensitization to allergens.
      These differences could be explained by air pollution. Respiratory symptoms were
      more common in a similar urban group of Polish children who were exposed to even
      higher levels of air pollution. These children, however, had a much lower
      prevalence of sensitization to allergens, as compared with the Swedish children.
      This indicates that differences in lifestyle and standard of living between
      western Europe and a former socialist country influences the prevalence of atopy.

PMID- 7812885
TI  - Immediate hypersensitivity to bakery, brewery and wine products in yeast
      sensitive atopic dermatitis patients.
AB  - Ultrafiltered (> 1000 Da) samples of beer, aged red wine, young white wine,
      sparkling wine and extracts of fresh wheat bread and dried rye bread were
      analysed by skin-prick test (SPT), radioallergosorbent test (RAST) inhibition,
      sodium dodecylsulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and
      immunoblotting to find out if they contain Saccharomyces cerevisiae (S.
      cerevisiae, baker's yeast) allergens. Serum pool consisting of S. cerevisiae
      positive sera was used in the assays. The results were compared with freeze-dried
      reference S. cerevisiae and cereal antigens. The beer, bread, red wine and
      sparkling wine extracts elicited immediate reactions. However, no evident
      correlation with suspected symptoms was observed. White wine extract caused
      reactions in four out of six atopic dermatitis (AD) patients with symptoms, and
      in five out of seven symptom-free AD patients and in two of the 24 controls. In
      SDS-PAGE, protein bands were found in wheat and rye bread extracts and beer. In
      IgE immunoblotting, however, no staining was seen with the S. cerevisiae positive
      sera suggesting that they were of cereal origin. In white wine and champagne
      extracts a non-specific staining was seen in the region 20 kDa representing, e.g.
      lectin-like activity. No baker's yeast antigen could be detected in brewery and
      bakery products with IgE-immunoblotting even in the excessively concentrated
      extracts. The IgE mediated allergy to baker's yeast alone should thus not lead to
      denial of bakery, brewery and wine products.

PMID- 7812886
TI  - Mite antigen in house dust: relationship with different housing characteristics
      in The Netherlands.
AB  - As part of a case-controlled study on the relationship between home dampness and
      respiratory symptoms of children, the concentration of the major allergen of
      Dermatophagoides pteronyssinus (Der p I) in floor dust and mattress dust in 516
      dwellings in the Netherlands was measured. A checklist, completed by the
      investigators, was used to obtain information on home and occupant
      characteristics, which may have an impact on the Der p I concentration in house
      dust. The geometric mean mite antigen concentrations were 2370 ng Der p I/g floor
      dust for the living room, 2201 ng Der p I/g floor dust for the bedroom and 5075
      ng Der p I/g mattress dust. In 86% of the houses the maximum concentration was
      higher than 2000 ng Der p I/g dust, that is regarded as representing a risk for
      genetically predisposed individuals for the development of specific IgE to house
      dust mite allergen. In 55% of the houses the maximum concentration exceeded
      10,000 ng Der p I/g dust, regarded as a risk factor for acute attacks of asthma
      for mite allergic patients. The Der p I concentrations in dust from carpeted
      floors were six to 14 times higher than in dust from floors with a smooth floor
      covering. Higher Der p I concentrations in floor dust were also significantly
      associated with increasing age of the dwelling and of the floor covering, with an
      increasing number of occupants, and with the absence of floor insulation. For
      mattress dust, the age of the mattress, the presence of an outer cavity wall and
      mechanical ventilation were important factors. Older mattresses had higher
      levels, and mattress dust from bedrooms with solid brick outer walls had higher
      levels than that from bedrooms with outer cavity walls. Mattresses in homes with
      continuous mechanical ventilation had almost twice lower levels than mattresses
      in homes with natural ventilation. There was a tendency towards higher Der p I
      concentrations in dust in homes with reported or observed signs of dampness. The
      Der p I concentrations in dust from carpeted bedroom floors and mattresses were
      positively associated with the average relative humidity in the bedroom over a
      period of 3-6 weeks in a subset of the homes where relative humidity was
      measured. Similar results were obtained using the concentrations of Der p I in
      ng/m2 instead of ng/g dust. The results obtained in this study are of importance
      for planning and evaluating allergen avoidance measures advised to mite allergic
      patients.

PMID- 7812887
TI  - Polymerase chain reaction quantification of cytokine messenger RNA expression in
      peripheral blood mononuclear cells of patients with acute exacerbations of
      asthma: effect of glucocorticoid therapy.
AB  - We have measured the expression of messenger ribonucleic acid (RNA) (mRNA)
      encoding interleukin-5 (IL-5), IL-4, IL-2 and interferon-gamma (IFN gamma) in
      peripheral blood mononuclear cells (PBMC) from 10 patients with acute
      exacerbations of asthma and nine non-asthmatic controls. Measurements were
      repeated in seven of the asthmatics following 7 days of oral glucocorticoid
      therapy. Total RNA was extracted from the PBMC, reverse transcribed using oligo
      (dT) primers and aliquots of the resulting complementary DNA (cDNA) amplified
      using the polymerase chain reaction (PCR) in the presence of cytokine-specific
      primers under non-saturating conditions. PCR products were quantified on a
      relative basis after Southern blotting and probing with radiolabelled internal
      oligonucleotide probes by computer assisted densitometry of blot autoradiographs.
      The relative amounts of IL-5 mRNA in PBMC from the asthmatic patients prior to
      glucocorticoid therapy were greater (P < 0.01) than those in PBMC from non
      asthmatic controls. In contrast, there were no differences in the relative
      amounts of IL-4, IL-2 and IFN gamma mRNA. In the asthmatics, the relative amounts
      of IL-5 mRNA correlated with the peripheral blood eosinophil counts (P = 0.02).
      After oral glucocorticoid therapy of the asthmatics, lung function improved and
      the relative amounts of PBMC IL-5 mRNA were reduced (P = 0.04) and no longer
      differed from those in PBMC from non-asthmatic controls. Glucocorticoid therapy
      was not associated with significant changes in the relative amounts of PBMC IL-4,
      IL-2 and IFN gamma mRNA. PBMC from atopic subjects contained significantly
      greater quantities of IL-4 mRNA (P = 0.04) but not IL-5, IL-2 and IFN gamma mRNA
      compared with non-atopic subjects regardless of their asthmatic status. We
      conclude that PBMC of patients with acute exacerbations of asthma demonstrate
      elevated expression of mRNA encoding IL-5, but not IL-2, IL-4 and IFN gamma and
      that the clinical improvement associated with glucocorticoid therapy is
      associated with a reduction of IL-5 mRNA expression. We further conclude that
      elevated expression in PBMC of mRNA encoding IL-4 is a feature of atopy but not
      of asthma. These observations suggest that IL-5 synthesis by activated T
      lymphocytes may be relevant to the pathogenesis of asthma, and that inhibition of
      this release by glucocorticoids may at least partly explain their therapeutic
      effect in this disease.

PMID- 7812888
TI  - Familial atopy in Australian pedigrees: adventitious linkage to chromosome 8 is
      not confirmed nor is there evidence of linkage to the high affinity IgE receptor.
AB  - Atopy frequently displays autosomal dominant inheritance and recent studies have
      favoured genetic linkage between atopy and the human chromosome 11q13. We have
      studied 12 extended families with aggregation of atopy consistent with autosomal
      dominant inheritance. The families have been studied for linkage of asthma and
      atopy to loci on chromosome 8p following the observation that one family
      suggested preliminary evidence of linkage to an anonymous hypervariable locus
      cloned from a DNA fingerprint and mapped to 8pter-p22. Subsequent analysis shows
      this putative linkage to be adventitious as the remaining 11 families do not
      support linkage between atopy and 8p. We have analysed the same families for
      evidence of linkage of atopy to loci on 11q13. In these families there is no
      evidence of association between atopy and the 11q loci stronger than that
      expected by chance alone; furthermore there is no suggestion that a subpopulation
      of these families display linkage between atopy and the loci. In addition neither
      the 8p loci nor the 11q loci exhibit evidence of linkage to atopy by affected sib
      pair analysis. This also conflicts with previously published data for 11q.

PMID- 7812889
TI  - Dermatophagoides pteronyssinus II-induced interleukin-4 and interferon-gamma
      expression by freshly isolated lymphocytes of atopic individuals.
AB  - Cytokines are known to play a major role in mediating many of the immunological
      and pathological features of allergic disease. Much of our understanding of
      cytokine production in response to allergens has come from studying allergen
      specific T cell clones following long-term in vitro culture. This has largely
      been due to the lack of sufficiently sensitive assays to measure allergen-induced
      cytokine production by freshly isolated peripheral blood mononuclear cells
      (PBMCs). Here we have used the polymerase chain reaction to amplify reverse
      transcribed interleukin-4 (IL-4) and IFN gamma mRNA expressed by allergen
      stimulated PBMCs from a variety atopic individuals. Using Der p II, a major
      allergen of the house dust mite (HDM) Dermatophagoides pteronyssinus, we have
      demonstrated that cells from HDM-sensitive atopic patients (n = 12), can be
      induced to express either IL-4 alone (three patients), IL-4 and IFN gamma (six
      patients), IFN gamma alone (two patients) or neither cytokine (one patient).
      Cells from 13 non-atopic control individuals were also stimulated with Der p II
      and cytokine mRNA production was studied. None expressed IL-4, while seven of 13
      transcribed IFN gamma. Our results suggest that atopic individuals have allergen
      reactive T cells at various stages of differentiation, with respect to the
      cytokines they produce. The use of this technique will aid in the further
      understanding of specific cellular hypersensitivity in allergic disease.

PMID- 7812891
TI  - The place of surgery in the management of rhinosinusitis.
AB  - Medication and surgery are often complementary in the treatment of
      rhinosinusitis. Surgery is often reserved for patients who have not responded to
      medical treatment. Where there is a significant mechanical obstruction of the
      airway or sinus ostea medical management is unlikely to succeed on its own. For
      those with a coexisting allergic rhinitis who need surgery, the maintenance of
      any improvement in the nasal airway or sinus drainage will partially depend on
      good compliance with medical treatment postoperatively. No condition illustrates
      the adage that 'to be a good surgeon you have to be a good physician' better than
      allergic rhinitis. Perhaps it should also be said that 'to be a good physician
      you should recognize when surgery has a role to play'.

PMID- 7812890
TI  - Nedocromil sodium 2% eye drops for twice-daily treatment of seasonal allergic
      conjunctivitis: a Swedish multicentre placebo-controlled study in children
      allergic to birch pollen.
AB  - This was a multicentre, double-blind, randomized group comparative study in which
      77 children, aged 6-16 years, received 2% nedocromil sodium eye drops and 72
      received placebo, one drop into each eye twice daily. The treatment period was 4
      weeks, covering the peak birch pollen season. Prior to the start of the season,
      patients who had attended the clinic the previous 2 years because of seasonal
      allergic conjunctivitis (SAC) to birch pollen, entered a one week baseline period
      during which symptoms were assessed, dairy cards completed, and routine sampling
      of blood and urine carried out. The double-blind treatment period then commenced
      at the onset of the birch pollen season. Patients/parents kept daily diary record
      cards of eye symptom severity and concomitant therapy. Conjunctivitis was mild in
      both treatment groups but nedocromil sodium was more effective than placebo in
      controlling symptoms. During the 2-3 weeks of peak pollen counts, this
      therapeutic effect was statistically significant for itching (P < 0.01), watering
      (P < 0.05) and total symptom score (P < 0.01), but was not significant for
      grittiness (P = 0.08) or redness (P = 0.06). Global opinions of efficacy showed
      no difference between treatments, due to a high placebo effect (however, the
      diary card data indicated a significant improvement with nedocromil sodium). We
      therefore conclude that nedocromil sodium 2% eye drops, administered twice daily,
      is an effective treatment for SAC in children.

PMID- 7812892
TI  - Nursing acceptance of a speech-input interface: a preliminary investigation.
AB  - Many new technologies are being developed to improve the efficiency and
      productivity of nursing staffs. User acceptance is a key to the success of these
      technologies. In this article, the authors present a discussion of nursing
      acceptance of computer systems, review the basic design issues for creating a
      speech-input interface, and report preliminary findings of a study of nursing
      acceptance of a prototype speech-input interface. Results of the study showed
      that the 19 nursing subjects expressed acceptance of the prototype speech-input
      interface.

PMID- 7812893
TI  - A computerized diabetes education module for documenting patient outcomes.
AB  - In this article, the authors describe the development, use, and evaluation of a
      computerized module that provides for uniform documentation of patient education
      and allows for measurement of specific educational outcomes. Within the first
      year of implementation, the diabetes education module was used in an outpatient
      clinic for one third of the patients with diabetes. Major content areas
      documented were blood glucose monitoring, nutrition, hypoglycemia, and foot care.
      Users indicated that the diabetes education module greatly improved their ability
      to review goals previously addressed and to identify unmet goals. The diabetes
      education module offers easy and quick access to critical teaching areas,
      specific objectives for each content area, and a method for documenting
      measurable outcomes for the individual patient.

PMID- 7812894
TI  - Time differences in handwritten and computer documentation of nursing assessment.
AB  - The increasing burden of documentation on nurses and the advent of improved
      computer technology prompted the development of a bedside documentation system.
      The time required for documentation of the nursing assessment and the number of
      observations recorded by the computer were compared with handwritten
      documentation. The time required for computer documentation using default
      charting of nursing assessment was significantly less than the time required for
      handwritten documentation. The number of observations recorded by computer was
      significantly greater than the number of observations recorded by hand.

PMID- 7812895
TI  - Differences between manual and computer-based methods for clinical learning
      assignments.
AB  - Two methods of assigning nursing students to clinical learning settings were
      compared for accuracy and speed. The first, a manually prepared method, was based
      on student preferences and experiential knowledge of nursing faculty. The second,
      a computer program designed for the project, used decision rules derived from
      ratings of student learning capabilities and ratings of the perceived demand for
      such capabilities by clinical settings. Ratings were assigned numerical values
      and were processed by the computer to obtain the best matches between students
      and settings. The same ratings were applied to the hand-prepared method after
      this assignment was completed. Comparison of the results showed that the best fit
      (least total numerical differences) between students and settings for the whole
      class was found by the computer, indicating that the computer method was
      superior. A completely randomized computer assignment that was run as an added
      source for comparison was much less effective than the assignment completed by
      hand, suggesting that human decision-making is an important factor in making
      clinical assignments. In terms of speed, 5.5 hours were used to prepare an
      assignment by hand and to make an adjustment; the computer completed the
      assigning task in less than 3 minutes. An alternate computing algorithm, used
      subsequently, completed the task in 3 seconds. The authors concluded that human
      judgment is necessary in making clinical assignments, but use of a tailored
      computer matching program can improve the quality of the decision making and can
      reduce the time and energy spent on this task.

PMID- 7812896
TI  - Laparoscopic Nissen Fundoplication: a minimal access alternative.
AB  - The preferred treatment of gastroesophageal reflux has traditionally been Nissen
      fundoplication. This involves an extensive abdominal or thoracic incision and
      subsequently results in patient discomfort, an extended recovery period, and
      increased overall costs. In the advent of laparoscopic advances surgical
      correction of symptoms of gastroesophageal reflux are now being offered through
      minimal access surgery. Increased patient satisfaction, decreased costs, and a
      quicker return to activities of daily living, suggest why laparoscopic Nissen
      fundoplication, (LNF) is fast becoming the preferred alternative to correction of
      gastroesophageal reflux disease. This article will review gastroesophageal reflux
      and describe one surgical method of laparoscopic correction. The role of the
      perioperative nurse and implementation of the nursing process regarding this
      surgical procedure will be highlighted.

PMID- 7812897
TI  - Laparoscopic assisted vaginal hysterectomy.
AB  - Laparoscopic Assisted Vaginal Hysterectomy (LAVH) is the latest advancement in
      gynecological surgery. It is proving to be a viable alternative to abdominal
      hysterectomy. Dr. J. Arneja and Dr. C. M. Shah have been doing LAVH since 1992.
      After completing 50 cases, a review of clinical experiences was undertaken.
      Indications for doing the procedures are almost identical, with fibroids being
      the most common indicator. A list of instruments required for doing LAVH, along
      with a diagram of the room set-up are included to help those nurses who are in
      the preliminary stages of doing LAVH. The procedure is described at length,
      beginning with positioning, prepping, and draping of the patient. A telephone
      audit with 25 patients who had a LAVH or Abdominal Hysterectomy is also reported.
      Complications, benefits, restrictions, and a cost comparison are discussed,
      including charts to show our results. The article concludes with an overview of
      the postoperative management of patients having LAVH.

PMID- 7812898
TI  - Endoscopy instruments: their role in delivering optimal patient care.

PMID- 7812899
TI  - Coaching as a framework for developing staff in the operating room.
AB  - This paper looks at coaching as a framework for facilitating the development of
      staff in the Operating Room. It defines coaching as an ongoing, face-to-face
      interaction between the learner and coach that supports and encourages employees
      to aspire to their best efforts. It stresses that coaches are not born but
      trained in life skills that they practice regularly.

PMID- 7812900
TI  - CAS discuss aspects of anaesthesia assistant role.

PMID- 7812901
TI  - The effects of minimally invasive surgery on the future of perioperative nursing.

PMID- 7812902
TI  - Diagnosis of patients with peripheral nerve disease.
AB  - Podiatrists have a unique opportunity to detect neuropathies at stages where
      specific treatment and measures to limit progression may be most beneficial. This
      article reviews neuropathic symptoms and signs that call for timely neurologic
      evaluation and intervention and outlines the essentials of a focused evaluation.
      The detailed clinical history and examination are still the mainstays for
      determining the specific diagnosis of most neuropathies and for distinguishing
      other neurologic disorders that may mimic neuropathies. Whenever the cause,
      severity, or very presence of a neuropathy remains uncertain, electromyography
      and nerve conduction studies performed by a well-trained physician experienced
      with neuromuscular diseases should be the mandatory next steps. Clinicians should
      expect electrophysiologic studies to define the specific pattern of neuropathy
      (fiber-length dependent versus multifocal) and the predominant pathologic process
      (axon loss versus demyelination), enabling them to restrict diagnostic tests to a
      rational, necessary, cost-effective, and productive minimum.

PMID- 7812903
TI  - Electrodiagnosis. An overview.
AB  - Electrodiagnostic consultation is a highly sensitive mechanism for the podiatrist
      to obtain functional information about the peripheral nervous system in the lower
      extremity. This article discusses the basic components of the electrodiagnostic
      consultation and the information that can be obtained through this testing.
      Additionally, it provides the podiatrist with guidelines for requesting
      consultation and interpreting the results.

PMID- 7812904
TI  - Intermetatarsal neuroma.
AB  - Interdigital neuroma, more classically referred to as Morton's neuroma, is
      considered one of the most common nerve problems affecting the foot. In this
      article, information regarding intermetatarsal neuroma is presented according to
      both a historical and clinical perspective. In addition, the author presents his
      own research on neuromas and describes conservative and surgical approaches in a
      logical format.

PMID- 7812905
TI  - Compartment syndromes causing neuropathy.
AB  - Compartment syndromes of the lower extremity can cause significant mobidity when
      appropriate treatment is not rendered. Paramount to the management of a
      compartment syndrome is a timely diagnosis. The physician must be intimately
      familiar with the anatomy as well as the signs and symptoms that a compartment
      syndrome presents. This familiarity can provide the opportunity for early
      diagnosis and treatment to prevent debilitating sequalae.

PMID- 7812906
TI  - Observations on 200 surgical cases of tarsal tunnel syndrome.
AB  - Surgical intervention for tarsal tunnel syndrome has been reported since the mid
      1960s. In 1975, the authors published their experiences using nerve conduction
      studies for the diagnosis and follow-up of tarsal tunnel syndrome. Since that
      time, the authors have operated on approximately 200 cases when conservative care
      failed to alleviate symptoms to a sufficient degree. In this article, a brief
      overview of our findings and follow-up is provided.

PMID- 7812907
TI  - Nerve entrapment causing heel pain.
AB  - Subcalcaneal heel pain is one of the most common foot ailments, yet the exact
      etiology is still controversial. Much attention and evidence have recently been
      presented implicating nerve entrapment as a causative factor for pain. Careful
      evaluation is needed to discern a nerve entrapment from other possible causes of
      heel pain. The majority of heel pain cases respond to thoughtful, conservative
      care; however, this care may take several weeks to months. In the few instances
      that surgery is necessary, the available reports show good to excellent results
      in most cases.

PMID- 7812908
TI  - Neurilemoma. A case report.
AB  - In this article, a case report of a patient presenting with "burning pain in the
      ball of her right foot" is detailed. Topics discussed include the diagnosis,
      surgical excision, and histopathology.

PMID- 7812909
TI  - Stroke and its manifestations in the foot. A case report.
AB  - CVA is a very common problem that can lead to lower extremity complications.
      Impairment in gait pattern occurs often due to spasticity and less frequently due
      to prolonged flaccidity. This problem is manifested by equinus, varus,
      equinovarus, and toe flexion deformities. Therefore, prevention or elimination of
      spasticity must be achieved. Various modalities have been used, both conservative
      and surgical. Nonsurgical interventions include range of motion and strengthening
      exercises, pharmacologic agents, local anesthetic and phenol motor point blocks,
      and the use of orthoses. Surgical intervention should be considered after
      conservative treatment has failed. The goal of treatment is to reduce the
      deforming force as a result of spasticity and to allow for almost normal function
      to be achieved. This includes tendon transfers, tendon lengthenings, tenotomies,
      and arthrodeses of small toe joints. Preoperatively, the extent and progression
      of spasticity must be determined because this may affect the rate of recurrence
      of the deformity following surgical correction. The combination of arthrodeses of
      the interphalangeal joints and flexor tendon release is the best option in the
      presence of a spastic deformity. Arthrodesis provides for stability at the joint,
      whereas a flexor release eliminates the deforming force. Failure to address the
      plantar-flexor force of the long flexors can lead to instability at the fusion
      site. This may in turn lead to nonunion and recurrence of flexion contracture as
      shown in the case report in this article.

PMID- 7812910
TI  - Surgical correction of hallux abducto valgus in a cerebral palsy patient. A 5
      year follow-up.
AB  - This article reviews the causes of foot deformities in patients with cerebral
      palsy. The authors underscore the necessity for a total evaluation of such
      patients. It is believed that the patient described in this article showed a
      recurrence of the hallux deformity due to failure to control the causative
      factors of this condition. Postoperative management with braces or orthoses may
      well have prevented recurrence.

PMID- 7812911
TI  - Expansion of the Ki-67 proliferative compartment correlates with degree of
      dysplasia in Barrett's esophagus.
AB  - BACKGROUND: Barrett's esophagus is a histologically defined premalignant lesion
      of the esophagus in which normal squamous epithelium is replaced by
      intestinalized columnar epithelium. In a multistep progression from Barrett's
      esophagus to fully developed carcinoma, accelerated proliferation may indicate or
      precede genomic instability and, therefore, may be an important factor in the
      pathogenesis and/or prediction of malignant transformation. Ki-67 is a nuclear
      antigen expressed in proliferating cells, (G1, S, G2, and M phases) but not in
      resting cells (G0 phase). This study was undertaken to determine if Ki-67
      expression correlates with the degree of dysplasia and if Ki-67 expression can
      help to differentiate those patients with or without dysplasia. METHODS: The Ki
      67 proliferation fraction in 87 paraffin embedded esophageal biopsies from 43
      patients with the Ki-67 antibody (MIB-1) was analyzed using immunohistochemistry.
      Using a computerized proliferation index program (QNA v2.54, Becton Dickinson
      Cellular Imaging Systems, Inc., Elmhurst, IL), a Ki-67 score was derived for the
      luminal surface, upper esophageal crypt, lower crypt, and underlying glandular
      zone of the columnar-lined esophagus. RESULTS: Significant differences in Ki-67
      scores were noted in each zone among different histologic categories: normal
      gastric ([NG] n = 17); Barrett's without dysplasia ([ND] n = 17); low grade
      dysplasia ([LG] n = 21); high grade dysplasia ([HG] n = 14); and adenocarcinoma
      ([CA] n = 5). The pattern of Ki-67 expression was associated strongly with each
      histologic category. The percentage of Ki-67 positive nuclei in each mucosal zone
      statistically separated high grade from low grade dysplasia (P < 0.001). In high
      grade dysplastic tissues, the Ki-67 positive nuclei were found predominantly on
      the surface epithelium and upper crypt zones, whereas in low grade dysplasia, the
      majority of Ki-67 positive nuclei were found in the lower crypt zone. The number
      of Ki-67 positive nuclei in each mucosal component also was significantly
      different in Barrett's esophagus without dysplasia when compared with Barrett's
      esophagus with low grade dysplastic tissues. (P < 0.001) Staining patterns of
      indefinite for dysplasia by H & E staining separated into several distinct
      patterns (five LG, seven ND, one NG) whereas six biopsies with low grade
      dysplasia had a Ki-67 expression pattern more consistent with that of high grade
      dysplasia. CONCLUSION: The Ki-67 staining pattern correlated with histologic
      findings in Barrett's esophagus and may represent an additional parameter for
      differentiating patients with or without dysplasia.

PMID- 7812912
TI  - Sequential chemotherapy and radiotherapy for patients with squamous cell
      carcinoma of the esophagus.
AB  - BACKGROUND: Despite surgical improvements the prognosis of patients with squamous
      cell carcinoma (SCC) of the esophagus remains poor, with a 5-year survival rate
      of less than 20%. Most patients do not undergo surgery with curative intent. The
      aim of this study was to assess the toxicity and efficacy of sequential
      chemoradiotherapy. METHODS: Between May 1986 and June 1991, 50 patients with
      nonmetastatic SCC of the esophagus were included in this study. Three patients
      had recurrence after surgery, 8 patients were classified Stage I disease, 24
      Stage II, 5 Stage III, and 10 Stage VI. Treatment consisted of cisplatin (100
      mg/m2 on Days 1 and 29), 5-fluorouracil (5-FU) (600 mg/m2 on Days 2-9 and Days 30
      33) and 30 Gy of radiotherapy (2 Gy x 15 on Days 8-26 and 30 Gy on Days 36-54).
      RESULTS: Thirty-seven patients (74%) received the whole treatment course;
      treatment was modified for 8 patients because of Grades III and IV hematologic,
      digestive, or renal toxicity. Five patients did not complete treatment because of
      disease progression or death. Median survival was 13 months; 1- and 2- year
      survival rates were 63% (49-75) and 36% (25-50), respectively. No late treatment
      complications were observed (in the 11 survivors after 2 years. CONCLUSIONS:
      Sequential chemoradiotherapy of SCC of the esophagus was well tolerated with
      acceptable acute morbidity and resulted in local control and survival results at
      least equivalent to those in trials of neoadjuvant chemoradiotherapy plus
      surgery.

PMID- 7812914
TI  - Intratumoral DNA heterogeneity of small hepatocellular carcinoma.
AB  - BACKGROUND: Intratumoral DNA heterogeneity provides important information
      regarding biologic and clinical behavior. The purpose of this study was to
      evaluate the incidence of DNA heterogeneity in small hepatocellular carcinoma
      (HCC) nodules. METHODS: The DNA content of 28 surgically resected small HCC
      nodules (< or = 3.0 cm) was measured using flow cytometry of fresh or frozen
      samples taken from different parts of each nodule with reference to the
      macroscopic features. RESULTS: Of the 28 small HCC nodules, 14 (50.0%) had only
      DNA diploid stemline characteristics. Five nodules (17.9%) manifested DNA diploid
      and DNA aneuploidy within the same tumor. Of the remaining nine nodules (32.1%)
      that showed only DNA aneuploidy, two contained tumor tissues with apparently
      different DNA content. Thus, DNA heterogeneity was found in 7 (25.0%) of 28
      nodules. DNA heterogeneity correlated well with macroscopic histologic features.
      All four early HCC were composed of only DNA diploid cells, whereas three of six
      nodule-in-nodule lesions were composed of DNA heterogeneous cells, in which the
      inner obviously cancerous nodule showed DNA aneuploidy and the outer well
      differentiated HCC portion demonstrated DNA diploid. Four of 18 overt HCC nodules
      showed DNA heterogeneity; 2 of these 4 nodules showed both diploid and aneuploid
      peaks, and the other 2 two showed different aneuploid peaks within the same
      nodule. CONCLUSIONS: DNA heterogeneity correlating with macroscopic features is
      found frequently even in small HCC nodules. Therefore, multiple sampling based on
      macroscopic features is required for the accurate assessment of DNA ploidy,
      particularly when the information about DNA ploidy is used as a prognostic
      indicator.

PMID- 7812913
TI  - Suramin in patients with metastatic colorectal cancer pretreated with
      fluoropyrimidine-based chemotherapy. A phase II study.
AB  - BACKGROUND: The results of conventional chemotherapy in metastatic colorectal
      cancer are discouraging, making it a logical target for new treatment approaches
      a necessary consideration. Suramin is a polysulfonated naphthylurea that binds to
      several cellular growth factors and has in vitro activity against human
      colorectal cancer cells. Therefore, this Phase II study of patients with
      metastatic colorectal cancer was conducted to evaluate its clinical activity.
      METHODS: Suramin was administered as a 6-day continuous infusion every week for 8
      consecutive weeks by using a computer-assisted dosing of Bayesan pharmacokinetics
      to maintain suramin plasma concentrations of 200-250 micrograms/ml. Twenty
      patients with metastatic colorectal cancer who were not responsive or in
      progression within 6 months after completing fluoropyrimidine-based chemotherapy
      entered the study. RESULTS: Toxicities included mostly Grade 1 and 2 fatigue,
      nausea and vomiting, peripheral neurotoxicity, creatinine elevation, and
      proteinuria. No objective responses were observed, but three of three patients
      who received 5-fluorouracil plus folinic acid after suramin achieved a partial
      response. CONCLUSIONS: These results indicate that suramin is inactive in
      patients with metastatic colorectal cancer pretreated with fluoropyrimidines.
      Pretreatment with suramin may have changed the biology of the tumor, sensitizing
      it to fluoropyrimidines. Studies to investigate this possibility are in progress.

PMID- 7812915
TI  - Value of serial carcinoembryonic antigen levels in patients with resectable
      adenocarcinoma of the esophagus and stomach.
AB  - BACKGROUND: Adenocarcinomas of the esophagus and the stomach are highly virulent
      and remain a major health problem worldwide; 5-year survival rates have not
      changed in the past 30 years. Recently, preoperative chemotherapy has been used
      to treat these adenocarcinomas. The authors evaluated the usefulness of serial
      serum carcinoembryonic antigen (CEA) levels in diagnosing these patients and
      compared the prognosis of patients with high or normal CEA levels. METHODS:
      Ninety consecutive patients with potentially resectable adenocarcinoma of the
      esophagus or stomach treated with preoperative chemotherapy were evaluated. Serum
      CEA levels were determined before registration, after each chemotherapy course,
      every 3 months for the first year after completion of all therapy, and every 6
      months thereafter for 5 years. RESULTS: The CEA positivity rate before
      chemotherapy was 22.2% (20/90); after chemotherapy, it dropped to 10.9% (9/82).
      An increasing CEA level predicted relapse and correlated well with liver, lung,
      or pleural involvement in some patients. Most patients with peritoneal
      involvement did not show elevated levels of CEA. Clinical responses correlated
      with declining levels of CEA in the patients who showed a negative conversion in
      CEA level after chemotherapy. CONCLUSIONS: An elevated serum CEA level enabled
      early detection of relapse in the absence of clinical symptoms in patients with
      adenocarcinoma of the esophagus or the stomach. The level of CEA was also useful
      in monitoring the response to chemotherapy in patients who had a high CEA level
      before treatment. Although the pre- and postchemotherapy CEA-positive group had a
      higher relapse rate than that of other group, the CEA level did not predict
      resectability or survival. Future research with labeled monoclonal anti-CEA
      antibodies may prove useful for certain groups of patients.

PMID- 7812916
TI  - Laryngeal dysplasia. A clinicopathologic study.
AB  - BACKGROUND: Histologic changes that may predict irreversible neoplastic
      transformation remain poorly defined for lesions of the larynx. To date, more
      than 20 schemes for the classification of laryngeal dysplasia have been proposed,
      yet no one system has gained wide acceptance. This has led to considerable
      confusion in defining the pathogenesis of this process and controversy in
      selecting the optimal management strategy of patients with premalignant changes
      of the larynx. METHODS: A detailed and systematic review was made of 125
      laryngeal biopsies from 62 patients with laryngeal squamous cell dysplasia who
      received long term follow-up (mean, 74 months). Various histopathologic
      parameters were assessed in an attempt to define the prognostic importance of
      each parameter for progression from atypia to invasive carcinoma. RESULTS: Five
      parameters were found to be significantly different when comparing lesions that
      progressed to carcinoma with those that remained stable or resolved: abnormal
      mitotic figures, mitotic activity, stromal inflammation, maturation level, and
      nuclear pleomorphism. Surface morphology, nucleolar prominence, and koilocytosis
      were not significantly different when comparing the two groups. Surface keratin
      formation did not suggest improved prognosis for patients with lesions with other
      features of dysplasia. CONCLUSIONS: These findings suggest that within the
      laryngeal glottis, severe keratinizing dysplasia occurs more frequently than does
      classic carcinoma in situ, and both entities likely represent intraepithelial
      neoplastic transformation.

PMID- 7812917
TI  - Philadelphia chromosome-negative chronic myelogenous leukemia with rearrangement
      of the breakpoint cluster region. Long-term follow-up results.
AB  - BACKGROUND: Five to 10% of patients with chronic myelogenous leukemia (CML) do
      not have the Philadelphia chromosome (Ph), but one-third of them have
      rearrangements of the breakpoint cluster region (BCR-positive). METHODS: The
      authors analyzed the characteristics, treatment response, and prognosis of 23
      patients with BCR-positive, Ph-negative CML, and compared them with patients with
      Ph-positive CML, Ph-negative BCR-negative CML and chronic myelomonocytic leukemia
      (CMML) treated during the same period. RESULTS: Seventeen patients had early
      chronic phase CML, 3 had late chronic phase, 2 had accelerated phase, and 1 had
      blastic phase. The median age was 44 years (range, 14-71 years), median platelet
      count was 402 x 10(9)/l, and median leukocyte count was 86 x 10(9)/l. Fourteen of
      the 17 patients with early chronic phase CML received alpha-interferon; 12 (86%)
      achieved complete hematologic remission. Median survival in chronic phase CML was
      60 months (range, 3-90+ months). Patients with Ph-negative BCR-positive CML and
      those with Ph-positive CML had similar characteristics and outcome. Compared with
      patients with Ph-negative BCR-negative CML and CMML, patients with Ph-negative
      BCR-positive CML and Ph-positive CML were significantly younger, had a
      significantly higher incidence of leukocytosis, thrombocytosis, and peripheral
      and marrow basophilia, and a significantly lower incidence of anemia,
      thrombocytopenia, marrow blast percent, and peripheral and marrow monocytosis.
      The median survival was 60 months for Ph-negative BCR-positive CML, 73 months for
      Ph-positive CML, 25 months for Ph-negative BCR-negative CML, and 9 months for
      CMML (P < 0.001). When analyzed adjusting for their stage, patients classified
      with Ph-negative BCR-positive CML. Stage I disease had a significantly better
      survival than did patients with Ph-negative BCR-negative CML (P < 0.02).
      CONCLUSIONS: Patients with Ph-negative BCR-positive CML are similar to those with
      Ph-positive CML and should be treated with the same approaches.

PMID- 7812918
TI  - Leukemic transformation of polycythemia vera and essential thrombocythemia
      possibly associated with an alkylating agent.
AB  - BACKGROUND: Leukemic transformation of polycythemia vera (PV) and essential
      thrombocythemia (ET) is influenced by the therapeutic modalities used. A high
      incidence of leukemic transformation was found among patients with PV or ET
      treated with an alkylating agent, carboquone (CQ). The study was conducted to
      assess the causal relationship between CQ and leukemic transformation of PV and
      ET. METHOD: Twenty-seven patients with PV and 29 with ET diagnosed from January
      1975 to August 1993 and whose clinical course could be followed comprised the
      members of this retrospective study. The patients were examined for the treatment
      administered, hematologic data, vascular complications, malignancies including
      leukemia, and eventual outcome. RESULTS: Eighteen patients with PV and 16 with ET
      were treated with CQ. The follow-up was 51-209 months for patients with PV and 28
      176 months for those with ET. Three patients with PV (17% of those treated with
      CQ) and 5 with ET (31% of those treated with CQ) had subsequent transformation to
      acute leukemia. The median period until transformation of patients with PV was 94
      months, whereas the median follow-up of patients without transformation was 146
      months (P < 0.01). The median total days of CQ administration and the median
      total dose of CQ were 2022 days and 1226 mg, respectively, for the patients with
      transformation and 1051 days (P < 0.05) and 435 mg (P < 0.01), respectively, for
      those without transformation. Likewise, the median follow-ups for patients with
      ET with or without transformation were 130 and 90 months, respectively; the
      difference was insignificant. The median total days of CQ administration and the
      median total dose of CQ were 2075 days and 1019 mg, respectively, for patients
      with transformation and 571 days (P < 0.05) and 231 mg (P < 0.01), respectively,
      for those without transformation. These observations suggest that CQ may be
      involved in the leukemic transformation of PV and ET. The subtypes of leukemia
      transformed from PV corresponded to M2 in two patients and to M4 in one. All five
      patients with ET were found to have megakaryoblastic features at transformation,
      and three were diagnosed as having leukemic subtype M7. Chromosomal abnormalities
      were found in all five patients (two PV and three ET) examined after leukemic
      transformation, showing multiple and complex abnormalities in four. CONCLUSION:
      Showing that both the total days of CQ administration and the total dose of CQ
      were larger for patients with PV or ET whose disease subsequently transformed to
      leukemia, with this study, a possible causal role of CQ in leukemic
      transformation of PV and ET is suggested.

PMID- 7812919
TI  - Desmoplastic neurotropic melanoma. A clinicopathologic analysis of 28 cases.
AB  - BACKGROUND: Desmoplastic neurotropic melanoma (DNM) is a rare variant of
      malignant melanoma, the natural history and histogenesis of which still are being
      defined. METHODS: The clinical and histologic features of 28 cases of DNM were
      studied. All published cases of DNM to date were reviewed. Paraffin sections from
      26 cases were investigated with a panel of 10 tissue markers. The ultrastructural
      features of seven cases were evaluated. RESULTS: A comparison of this study's
      findings with that of other published cases revealed many similarities regarding
      clinical and pathologic findings and outcome. The patients were white (15 men:13
      women; mean and median age, 59 years; range, 22-83 years). Most tumors were
      located on the head and neck (75%) and were nonpigmented (57%). An associated
      intraepidermal melanocytic proliferation was identified in 85% of the patients
      (lentigo maligna in 56%). Histologically, the dermal tumors were composed of
      tapered, nonpigmented spindle cells in peripheral nerve sheath patterns
      resembling neuromas, schwannomas, neurofibromas, and perineurial proliferations
      accompanied by variable neurotropism and desmoplasia; desmoplasia was the most
      notable feature in most tumors. The mean depth of tumor invasion was 4.1 mm
      (range, 0.32-9.0 mm). Tumors with continuity between the epidermal and dermal
      components had a significantly thinner depth of invasion and a more extensive
      intraepidermal melanocytic proliferation than those tumors with a grenz zone
      between the two components (2.3 mm vs. 4.6 mm, P = 0.015). Mitotic activity
      ranged from 0/HPF in 10 cases, 1-6/high power field (HPF) in 12 cases, and to
      greater than 6/HPF in 4 cases. An ulcer was present in 5/27 tumors, regression in
      4/27, a microsatellite in 1, and brisk and had nonbrisk tumor infiltrating
      lymphocytic responses in 2 and 14, respectively. Vimentin was uniformly positive
      and keratins AE1.3 and Cam 5.2 and Leu-7 were uniformly negative. S100 protein,
      also uniformly positive, had patchy reactivity in most tumors that expressed EMA
      (43%). Smooth muscle actin (52%), neuron-specific enolase (42%), and FXIIIa (30%)
      had patchy positivity. HMB-45 was reactive only in the epidermal and superficial
      papillary dermal component in 21% of cases. Ultrastructurally, the common
      features were long, often intertwining cellular processes, intercellular
      junctions, and discontinuous basal lamina. Melanosomes were not identified.
      Follow-up data available on 26/28 patients (mean, 36 months; median, 24 months;
      range, 5-132 months) showed 20 (70%) alive without disease, 2 alive with disease
      and 3 dead from disease. Seven patients had recurrent local tumor (multiple in
      four); four had lymph node metastases, and three had visceral metastases.
      Patients with recurrent disease of any type had significantly thicker tumors (5.4
      mm vs. 3.4 mm, P = 0.046) and were more likely to have an ulcerated tumor (P =
      0.03). Actuarial 5-year survival for tumors with greater than a 4-mm thickness
      was 72%, which was greater than that for other types of melanoma with greater
      than a 4-mm thickness. CONCLUSIONS: Desmoplastic neurotropic melanomas are
      neuroectodermal tumors that usually arise from an intraepidermal melanocytic
      proliferation but rarely develop de novo in the dermis. Schwannian and
      perineurial differentiation may account for the desmoplasia and neurotropism
      encountered in these neoplasms. Desmoplastic neurotropic melanomas present at a
      more advanced stage locally and may be associated with a better survival than
      associated with conventional melanomas of similar depth of invasion.

PMID- 7812920
TI  - Improved survival of patients with melanoma with an antibody response to
      immunization to a polyvalent melanoma vaccine.
AB  - BACKGROUND: Melanoma vaccine treatment appears to slow the progression of
      melanoma in some patients, particularly in patients in whom it stimulates
      cellular antimelanoma immune responses. The relationship of vaccine-induced
      antibody responses to clinical outcome is less clear. The purpose of this study
      was to investigate the clinical relevance of antibody responses to melanoma
      vaccine immunization. METHODS: Eighty-two evaluable patients with surgically
      resected American Joint Committee on Cancer Stage III malignant melanoma were
      immunized to a partially purified, polyvalent, melanoma antigen vaccine.
      Antimelanoma antibodies were measured by immunoprecipitation and sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis analysis before vaccine treatment and
      1 week after the fourth immunization. RESULTS: Vaccine treatment induced or
      augmented antibody responses to melanoma in 32 (39%) of the patients. The
      antibodies were directed to one or more antigens of 38-43, 75, 110, 150 and/or
      210 kDs, which previously have been shown to be expressed preferentially in
      cultured human melanoma cells. The median disease free survival of patients with
      a vaccine-induced antibody response to one or more of these antigens was 5.4
      years compared with 1.4 years for nonresponders (P = 0.06), and 5-year overall
      survival was 71% compared with 44%, respectively (P = < 0.01). As determined by
      Cox multivariate analysis, the difference in overall survival was independent of
      disease severity or of immunologic competence as evaluated by ability to be
      sensitized to dinitrochlorobenzene. The difference in survival between antibody
      responders and nonresponders improved with time. CONCLUSIONS: The antibody
      response to vaccine treatment is an immune marker of vaccine activity that
      appears to be predictive of a later reduction in the recurrence of melanoma and
      is unrelated to the vaccine's ability to induce cellular immune responses. This
      finding suggests that vaccine treatment may be effective in slowing the
      progression of melanoma in some patients and that the protective effect is
      mediated partly by vaccine-induced antimelanoma antibodies.

PMID- 7812921
TI  - The etiology and prediction of breast cancer. Fourier transform-infrared
      spectroscopy reveals progressive alterations in breast DNA leading to a cancer
      like phenotype in a high proportion of normal women.
AB  - BACKGROUND: The authors previously have shown by gas chromatography-mass
      spectrometry that the hydroxyl radical (.OH) induces alterations in the DNA base
      structure of the female breast, which are premalignant markers of breast cancer.
      Fourier transform-infrared (FT-IR)-spectroscopy also has a high potential for
      revealing a broad array of structural changes in DNA that may provide important
      new insight into breast cancer etiology and prediction. METHODS: DNA from normal
      reduction mammoplasty tissue, invasive ductal carcinoma, and nearby
      microscopically normal tissue was analyzed by FT-IR spectroscopy. Statistical
      models based on DNA spectral properties were developed and compared with a
      statistical model previously used with base modifications. RESULTS: Substantial
      differences were found in the spectral properties of DNA from women with normal
      and cancerous breast tissue, indicating an ability to discriminate cancerous
      tissue from noncancerous tissue with a sensitivity and specificity of 83%. Most
      importantly, the normal population was divided into subgroups in which a
      nonrandom progression was identified and a cancer-like DNA phenotype that was
      highly correlated (r > or = 0.90) with that of the patients with cancer was
      exhibited in 59% of the women. The spectral data, which also were highly
      correlated with the base-model data, were used to establish a model for
      predicting the probability of breast cancer. Consistent with the high cancer
      reoccurrence rate in the ipsilateral breast, 8 of 10 of the microscopically
      normal tissue specimens remaining after tumor excision were classified as
      cancerous using this model. CONCLUSIONS: Progressive structural changes in the
      DNA of the normal female breast, leading to a premalignant cancer-like phenotype
      in a high proportion of women, are the basis for a new paradigm for understanding
      the etiology of breast cancer and predicting its occurrence at early stages of
      oncogenesis. The results also suggest therapeutic strategies for potentially
      reversing the extent of DNA damage, which may be useful in disease prevention and
      treatment.

PMID- 7812922
TI  - Association of human leukocyte antigen-B1*03 with cervical cancer in Japanese
      women aged 35 years and younger.
AB  - BACKGROUND: An association of human leukocyte antigen (HLA)-DQw3 alleles with
      squamous cell carcinoma (SCC) of the cervix has been reported in some European
      populations, but the significance of HLA-DQw3 has not been examined in other
      populations to the authors' knowledge. The interaction between HLA-DQw3 and human
      papillomavirus (HPV) in SCC remains to be clarified. METHODS: To elucidate the
      association of HLA-DQ alleles with SCC of the cervix, DNA samples extracted from
      blood lymphocytes of 23 patients with SCC were amplified by the polymerase chain
      reaction (PCR) using specific primers for the DQB1 genes, and then, each HLA-DQB1
      genotype was defined by digestion with restriction enzymes. Human papillomavirus
      typing also was performed in all cases by PCR, using specific primers for the E6
      regions of cancer-associated HPV types (HPV 16, 18 and 33). RESULTS: Twenty
      patients (87%) carried a DQB1 gene-encoding HLA-DQw3, compared with 49.4%
      Japanese control subjects in the International Histocompatibility Workshop panel
      (P = 0.0003). Human papillomavirus 16 or HPV 18 DNA was detected in 86% of the
      patients. In 13 of the patients with invasive carcinoma with HPV, a high
      incidence of not only HLA-DQw3 but also of HLA-DQw1 was observed compared with
      that in control subjects (P = 0.0019, P = 0.047, respectively). The correlation
      between DQB1*03 alleles and HPV infection was not statistically significant.
      CONCLUSION: The frequency of HLA-DQw3 alleles was higher in the authors' patient
      group than in the control group, suggesting that the HLA-DQw3 molecules may
      influence the development of SCC of the cervix in young Japanese women. In the
      patients with HPV-positive invasive carcinoma, the association with HLA-DQw1
      molecules suggested that it also may influence the progression of SCC.

PMID- 7812923
TI  - Adult Wilms' tumor. Report of two cases and review of the literature.
AB  - BACKGROUND: Wilms' tumor is rare in adults. The recommended treatments for
      patients with Stage II adult Wilms' tumor with favorable histology (FH)
      nephroblastomas are conflicting. METHODS: Two patients with Stage II, favorable
      histology, adult nephroblastomas are described. Current treatment modalities are
      discussed and the literature is reviewed. RESULTS: The first patient, a 52-year
      old woman, probably had a late local relapse of a Wilms' tumor 21 years after
      nephrectomy because of a renal tumor originally diagnosed as reticular sarcoma.
      In this case, a recurring or an extrarenal Wilms' tumor should have been
      considered. After the tumor was removed, the patient received adjuvant
      chemotherapy with dactinomycin and vincristine and was disease free 44 months
      after diagnosis. The Wilms' tumor in the second patient, a 33-year-old woman, was
      discovered accidentally and classified as Stage II/FH based on preoperative
      biopsy. She was treated with radical nephrectomy and adjuvant chemotherapy with
      dactinomycin and vincristine. This patient was disease free 24 months after
      surgery. CONCLUSIONS: Surgery and two-drug chemotherapy with dactinomycin and
      vincristine is suggested for patients with Stage II adult Wilms' tumor with FH
      nephroblastomas.

PMID- 7812924
TI  - Bacillus Calmette-Guerin treatment of existing papillary bladder cancer and
      carcinoma in situ of the bladder. Four-year results. The Bladder Cancer BCG Study
      Group.
AB  - BACKGROUND: Intravesical instillation therapy of Bacillus Calmette-Guerin (BCG)
      has become a standard treatment for carcinoma in situ (CIS) of the urinary
      bladder. However, there have been few reports concerning the direct effect of BCG
      on existing tumors classified as Ta or T1. In the first stage of this clinical
      study, 157 patients were treated with BCG intravesical instillation (Tokyo 172
      strain [BCG Co. Ltd., Tokyo, Japan]; 80 mg weekly for eight times) by our Study
      Group. The efficacy on existing tumors was a complete response (CR) rate of 84.4%
      and 66.4% and a partial response (PR) of 6.3% and 20.8% for 32 cases of CIS and
      125 cases of Ta or T1 tumors, respectively. METHODS: In the second stage of this
      study, the authors investigated the outcome of the 138 patients who had achieved
      CR or PR in the first stage. One hundred twenty (87.0%) of the patients were
      followed fully. Of those patients, 52 were randomized to receive prophylactic
      (maintenance) therapy consisting of BCG of 40 mg monthly for 12 times (Group A),
      whereas 55 were randomized to an untreated control group (Group B). Thirteen
      other patients refused to be randomized and were followed without prophylactic
      instillation. RESULTS: The median follow-up period was 48 months for Group A and
      42 months for Group B. In Groups A and B, the beneficial effect of the BCG
      therapeutic instillation persisted for a long time, and the 3-year nonrecurrence
      rate was 77.6% in Group A and 74.2% in Group B. Disease progression was observed
      rarely. CONCLUSION: For patients in whom transurethral resection of tumors of the
      bladder (TUR-Bt) alone is unlikely to eliminate the tumor, intravesical BCG is
      potentially the treatment of choice.

PMID- 7812925
TI  - Prevalence and predictors of continued tobacco use after treatment of patients
      with head and neck cancer.
AB  - BACKGROUND: Patients with head and neck cancer who continue to smoke after
      diagnosis and treatment are more likely than patients who quit to experience
      tumor recurrence and second primary malignancies. Therefore, information about
      patients' smoking status and the factors associated with continued tobacco use
      are important considerations in the comprehensive care patients with head and
      neck cancer. METHODS: Study participants were 144 patients with newly diagnosed
      squamous cell carcinomas of the upper aerodigestive tract who underwent surgical
      treatment, with or without postoperative radiotherapy or chemotherapy, 3-15
      months before assessment of their postoperative tobacco use. RESULTS: Among the
      74 patients who had smoked in the year before diagnosis, 35% reported continued
      tobacco use after surgery. Compared with patients who abstained from smoking,
      patients who continued to use tobacco were less likely to have received
      postoperative radiotherapy, to have had less extensive disease, to have had oral
      cavity disease, and to have had higher levels of education. Hierarchical
      regression analysis indicated that most of the explained variance in smoking
      status could be accounted for on the first step of analysis by disease site.
      Interest in smoking cessation was high, and most patients made multiple attempts
      to quit. CONCLUSIONS: Although the diagnosis of a tobacco-related malignancy
      clearly represents a strong catalyst for smoking cessation, a sizable subgroup of
      patients continue to smoke. Patients with less severe disease who undergo less
      extensive treatment are particularly at risk for continued tobacco use. These
      data highlight the importance of developing smoking cessation interventions
      designed to meet the demographic, disease, treatment, and tobacco-use
      characteristics of this patient population.

PMID- 7812926
TI  - Cancer risk after splenectomy.
AB  - BACKGROUND: Splenectomy may have an impact on immunologic function. To the
      authors' knowledge, the only previous epidemiologic study investigating cancer
      risk among patients splenectomized because of trauma reported no increased cancer
      risk. In contrast, several investigations have suggested that splenectomy in
      patients with Hodgkin's disease increases the risk for secondary leukemia
      independent of treatment. METHODS: To evaluate the cancer risk of patients who
      underwent splenectomy after traumatic rupture of the spleen, 1103 patients were
      identified between 1977 and 1989 through Danish hospital discharge records.
      Another 5212 splenectomized patients also were identified to perform additional
      analyses for assessing cancer risk subsequent to splenectomy for nontraumatic
      indications including benign and malignant conditions. Cancer occurrence was
      determined by performing a linkage to the Danish Cancer Registry. For comparison,
      expected numbers of cases of cancer were calculated from national cancer
      incidence rates. RESULTS: The number of cancer cases observed among posttraumatic
      splenectomized patients matched the expected number (relative risk = 1.0; n = 20;
      95% confidence interval = 0.6-1.6) in an average follow-up of 6.8 years.
      Additional analyses identified possible excesses of a number of site-specific
      neoplasms among certain subgroups of patients undergoing splenectomy for
      nontraumatic reasons, but the numbers in the subgroup analyses were small.
      CONCLUSIONS: No increased risk for cancer was observed among patients who
      underwent splenectomy because of trauma. However, an increased risk for some
      specific cancer sites was found in patients who underwent splenectomy for
      nontraumatic reasons, although the effect of treatments for underlying disease
      and lifestyle habits such as cigarette smoking could not be ruled out in
      explaining these excess risks.

PMID- 7812927
TI  - Abnormalities in the PRAD1 (CYCLIN D1/BCL-1) oncogene are frequent in cervical
      and vulvar squamous cell carcinoma cell lines.
AB  - BACKGROUND: CYCLIN D1, a cell-cycle control gene, recently has been shown to be
      identical to an oncogene alternatively known as BCL-1 and PRAD1 and implicated in
      centrocytic lymphomas and parathyroid adenomas, respectively. PRAD1 complexes to
      the product of the retinoblastoma (Rb) tumor suppressor gene, an event followed
      by Rb inactivation. Squamous cell carcinomas of the cervix and vulva are
      gynecologic tumors in which human papillomaviruses have been implicated as an
      initiating event, and proteins derived from these viruses also complex with an
      inactivate Rb. Because of the overlap in some of the molecular processes mediated
      by human papillomaviruses and by the PRAD1 oncogene, the authors analyzed the
      PRAD1 (CYCLIN D1/BCL-1) genomic structure and expression in vulvar and cervical
      squamous cell carcinoma cell lines. METHODS: PRAD1 DNA and PRAD1 mRNA expression
      were assessed by Southern and Northern blotting, respectively, in 13 squamous
      cell carcinoma cell lines of gynecologic origin (10, cervical cancer; 3, vulvar
      cancer). RESULTS: We found low baseline levels of a 4.5-kb PRAD1 transcript in a
      series of control cell lines, which were derived from normal fibroblasts, various
      hematologic malignancies, and a choriocarcinoma. PRAD1 mRNA overexpression (> or
      = 10-fold greater than that in control lines) was seen in all three vulvar
      carcinoma cell lines, two of which also showed amplification (5-fold and > 10
      fold) of PRAD1 genomic sequences. Abnormalities of PRAD1 also were seen in 4 of
      the 10 cervical cancer cell lines and included overexpression of PRAD1
      transcripts (3-9-fold) in 3 lines and rearrangement of PRAD1 DNA in an additional
      line that, however, did not shown any aberration in PRAD1 mRNA as discernible by
      Northern blotting. PRAD1 abnormalities were observed in three of the four
      cervical cell lines derived from metastatic sites and in one of the six cervical
      lines derived from primary tissue. CONCLUSIONS: Seven of 13 squamous cell lines
      of gynecologic origin showed abnormalities of PRAD1. These abnormalities included
      amplification and rearrangement of DNA and overexpression of mRNA. The role of
      PRAD1 as a cell-cycle regulatory gene and its interactions with the Rb tumor
      suppressor gene suggests that PRAD1 deregulation may be a significant molecular
      event in the evolution of these tumors.

PMID- 7812928
TI  - Modulation of natural killer cell-mediated cytotoxicity by tamoxifen and
      estradiol.
AB  - BACKGROUND: The nonsteroidal antiestrogenic drug, tamoxifen, inhibits the growth
      of estrogen receptor-positive tumors by interfering with the growth-stimulatory
      effect of estradiol. However, there is compelling evidence that tamoxifen
      treatment also is beneficial for patients with estrogen receptor-negative tumors.
      The hypothesis that tamoxifen is capable of enhancing the immunologic defense of
      tumor-bearing hosts was been investigated as a possible method for targeting
      receptor-negative neoplasms. METHODS: Natural killer (NK) cells in the spleen of
      female Fisher and Wistar-Furth rats were used against the YAC-1 murine lymphoma
      target in 51Cr-release assays. The effect of various concentrations of estradiol
      and tamoxifen (1 nM-1 microM) and of the metabolic inhibitors actinomycin D and
      cyclohexamide on target-cell killing was investigated. RESULTS: Tamoxifen
      enhanced and estradiol inhibited killing if applied for the entire 5 hours of the
      cytotoxic reaction. When applied jointly in this experimental setup, estradiol
      interfered with the enhancing effect of tamoxifen. Pretreatment of target cells
      with tamoxifen led to highly significant enhancement of cytotoxicity; estradiol
      also enhanced target cell killing, but to a lesser extent. After joint treatment,
      the level of cytotoxicity was comparable with that obtained with tamoxifen alone.
      Both pharmacologic (100 nM and 1 microM) and physiologic (1 or 10 nM)
      concentrations of estradiol and equimolar tamoxifen enhanced target cell lysis.
      However, pharmacological levels of estradiol inhibited effector cells when
      applied alone or in combination with tamoxifen. Highly significant enhancement of
      target-cell destruction occurred if both target and effector cells were
      pretreated with tamoxifen, whereas estradiol treatment of both cell types led to
      slight enhancement or no effect on cytotoxicity. Treatment of the target cells
      with actinomycin D or cycloheximide inhibited the lysis of untreated and
      tamoxifen- or estradiol-exposed cells. Treatment of YAC-1 target cells with
      tamoxifen or estradiol also enhanced the NK cell-mediated release of the nuclear
      label, 3H-thymidine, indicating DNA degradation. Similarly treated P815 cells
      resisted lysis by NK cells, but showed sensitization when the NK cells were
      stimulated by interleukin-2 for 48 hours before the lytic reaction. Estradiol and
      tamoxifen changed the kinetics of 3H-thymidine incorporation by YAC-1 cells, but
      the cells were capable of growing with the highest drug concentrations (1 microM)
      used in the cytotoxicity experiments. YAC-1 cells have no cytosolic estradiol
      receptors and are weakly positive for cytosolic progesterone receptors.
      CONCLUSIONS: These experiments indicate that NK cell-mediated target-cell
      destruction can be enhanced by tamoxifen primarily through sensitizing the target
      for lysis. Estradiol also sensitizes the target but inhibits the effector cells
      simultaneously so that little or no change results in cytolysis. Target-cell
      sensitization is not mediated by classical estrogen receptors and requires the
      active metabolic participation of the cells treated. A likely mechanism of this
      phenomenon is priming the target cell for apoptosis.

PMID- 7812929
TI  - Accuracy of current imaging modalities in the diagnosis of synchronous bilateral
      Wilms' tumor. A report from the National Wilms Tumor Study Group.
AB  - BACKGROUND: Five percent of patients with Wilms' tumor will present with
      bilateral disease. Recent reports suggest that preoperative imaging studies can
      exclude contralateral disease reliably, obviating the need for formal surgical
      exploration of the contralateral kidney. This study was undertaken to determine
      the accuracy of preoperative imaging in diagnosing bilateral Wilms' tumor.
      METHODS: The charts of 122 patients with synchronous bilateral Wilms' tumor
      enrolled in National Wilms Tumor Study-4 were reviewed. With the exception of one
      child, all had an abdominal computed tomography (CT), ultrasound, or magnetic
      resonance imaging performed. RESULTS: There were nine patients (7%) in whom the
      diagnosis of bilaterality was missed by the preoperative imaging studies. All but
      one of the missed lesions were small, five less than 1 cm and three 1-3 cm. The
      accuracy of each imaging modality was correlated with tumor size. Computed
      tomography was more sensitive in detecting bilaterality than ultrasound. However,
      there was not a single study that was able to detect more than 50% of lesions
      less than 1 cm in greatest dimension. CONCLUSIONS: This review indicates that
      even with current advances in imaging technology, synchronous bilateral Wilms'
      tumor will go unrecognized in 7% of patients if formal exploration of the
      contralateral kidney is omitted. Although this represents a small percentage of
      all patients presenting with Wilms' tumor, preoperative diagnosis of bilaterality
      is essential if parenchymal-sparing procedures are to be performed. Until a more
      reliable indicator of bilateral disease is found, exploration of the
      contralateral kidney continues to be recommended.

PMID- 7812930
TI  - Alanine metabolism in rats bearing the Yoshida AH-130 ascites hepatoma.
AB  - Rats bearing the Yoshida AH-130 ascites hepatoma, a cachectic rat tumour, showed
      signs of important muscle wasting with reduced muscle weights. This phenomenon
      was associated with a decreased rate of in vivo alanine oxidation as measured by
      the production of 14CO2 from [U-14C]alanine intragastrically administered. It was
      later found that the decreased amino acid oxidation was associated with a reduced
      uptake in skeletal muscle as measured in incubated soleus muscles, thus
      suggesting that the decreased in vivo oxidation is basically due to a reduced
      oxidation of the amino acid in skeletal muscle. The decrease in alanine oxidation
      in the tumour-bearing animals was also associated with higher circulating alanine
      concentrations in their blood. In addition, tumour-bearing rats presented a lower
      (26%) protein synthetic rate in skeletal muscle, as measured by the incorporation
      of [14C]phenylalanine into muscle protein. The addition of insulin to the
      incubation medium abolished the lower rate of protein synthesis, thus suggesting
      a greater response to this hormone by the muscle of tumour-bearing rats. In
      conjunction with a reduced protein synthesis, tumour-bearing rats showed a
      clearly enhanced rate of protein degradation in isolated skeletal muscles. The
      results presented confirm previous observations suggesting that the skeletal
      muscle of tumour bearing animals is in a profound negative nitrogen balance which
      partially accounts for the wasting observed in the tissue. In addition, the
      present study allows us to conclude that, in spite of the increased alanine
      utilization for both gluconeogenesis and tumour growth, the oxidation of alanine
      by the whole animal is decreased in the tumour-bearing rats. This seems to be
      associated with a decreased ability of skeletal muscle to handle this amino acid.

PMID- 7812931
TI  - Effect of route of administration of environmental methylating agents on 7
      methylguanine formation in white blood cells and internal organs: implications
      for molecular epidemiology.
AB  - The measurement of 7-methylguanine (7-meG) in white blood cells (WBC) is a
      promising biomarker of individual human exposure to environmental methylating
      agents. To test the validity of using WBC as a surrogate dosimeter for internal
      tissues, levels of 7-meG were measured in rat WBC, liver and target organs for
      carcinogenesis 16 h after oral administration of several methylating carcinogens
      (DMN, DMH, NNK, NMBA). 7-MeG was detected in WBC DNA but levels were far lower
      than in internal organs. While the ratio between 7-meG formation in target organs
      and WBC was highly variable depending on the carcinogen administered, the ratio
      between 7-meG in the liver and WBC was in the same order of magnitude for each
      carcinogen, ranging from 81 to 143. In addition, levels of 7-meG in the liver and
      WBC within individual animals were highly correlated (r = 0.94, P < 0.0001).
      These results confirmed our previous observations with the same carcinogens after
      intraperitoneal injection. In order to assess if the lower level of 7-meG in WBC
      was a result of a low metabolism of methylating agents in WBC, microsomes were
      prepared from control rat lymphocytes and DMN demethylase activity was measured.
      The total amount of microsomal proteins was extremely low, especially in
      comparison with hepatic cells, and the enzymatic activity was less than 0.48 nmol
      HCHO/min/mg protein, while an activity of 1.26 nmol HCHO/min/mg protein was
      measured in liver microsomes. Taken together, these results suggest that the
      presence of 7-meG in WBC DNA reflects an exposure to methylating agents; the
      level of 7-meG in WBC seems predictive of the level of adduct in the liver,
      possibly because active methylating species are formed in the liver and then
      transferred into the hepatic circulation, where the WBC are exposed. It is now
      important to examine this relationship in humans where exposures are generally to
      lower levels of carcinogens over long time periods.

PMID- 7812932
TI  - Colocalization of prolactin and proliferating cell nuclear antigen in the
      anterior pituitary during estrogen-induced pituitary tumors.
AB  - Chronic estrogen treatment induces prolactin (PRL)-secreting pituitary tumors in
      laboratory animals. To determine earlier events of tumorigenesis, we studied cell
      proliferation in the pituitary following 7-30 days of estrogen administration in
      Fischer 344 rats. Immunohistochemical localization of proliferative cells by
      proliferating cell nuclear antigen (PCNA) staining and lactotropes by PRL
      staining revealed that estrogen treatment caused a time-dependent increase in the
      number of proliferative cells and lactotropes. Although the increase in
      lactotropic cell number paralleled the increase in PCNA-reactive cell number,
      only approximately 30% of lactotropes reacted simultaneously with the PCNA
      antibody. These results indicate that a subset population of lactotropes
      proliferates under the influence of estrogen during tumorigenesis.

PMID- 7812933
TI  - The effect of inducers and inhibitors of urethane metabolism on its in vitro and
      in vivo metabolism in rats.
AB  - The activation of urethane (ethyl carbamate) is important in its exerting its
      carcinogenic effect. Rats were treated with inducers and inhibitors of urethane
      metabolism, and the conversion of [carbonyl-14C]urethane to 14CO2 in vivo was
      measured. The cytochrome P-450 inducers, phenobarbital and beta-naphthoflavone,
      and esterase inhibitor, paraoxon, were without effect while the CYP2E1 inhibitor,
      diethyldithiocarbamate, decreased metabolism to about 3% of control. Ethanol
      administered acutely inhibited urethane metabolism. Pyridine, shown previously to
      enhance this metabolism in microsomal preparations, greatly inhibited it in vivo.
      The discordant results between the in vitro and in vivo studies may be related to
      the presence of pyridine acting as an inhibitor in whole animals and suggest that
      caution is needed in extrapolating from in vitro results to in vivo implications.

PMID- 7812934
TI  - Initiation-stage enhancement by uracil of N-ethyl-N-hydroxyethylnitrosamine
      induction of kidney carcinogenesis in rats.
AB  - The present study was conducted to clarify the effects of N-ethyl-N
      hydroxyethylnitrosamine (EHEN) and uracil in combination on renal carcinogenesis
      in female F344 rats. Group 1 animals (n = 30) received a 3-week simultaneous
      administration of 0.05% EHEN and 3% uracil, and group 2 (n = 26) 0.05% EHEN with
      a lower 1.5% dose of uracil. Group 3 (n = 30) was treated with 0.05% EHEN alone
      and group 4 (n = 28) received only 3% uracil for 3 weeks. In all the above four
      groups, the rats were given basal diet and water without chemical addition for a
      48-week period after the 3-week treatment period. Group 5 (n = 33) received no
      chemicals for the entire 52 weeks. At the end of week 52, renal adenocarcinomas
      were found in 53%, 31% and 13% of the rats in groups 1, 2, and 3, respectively.
      The present study thus demonstrated that simultaneous administration of uracil
      enhances the occurrence of EHEN-induced renal adenocarcinomas in rats.

PMID- 7812935
TI  - Inhibition of invasion of murine mammary carcinoma cells by the tyrosine kinase
      inhibitor genistein.
AB  - Tyrosine kinases are ubiquitous enzymes that have been shown to be involved in
      many cellular functions, including growth and differentiation. Recent studies
      have shown that they are also involved in integrin signal transduction pathways.
      Since integrins are known to be involved in cellular adhesion and thus in
      invasion and metastasis, the possible involvement of tyrosine kinases in invasion
      was tested. Tumor cell invasion was measured using filter inserts coated with
      Matrigel, a substance that closely resembles the natural basement membrane. A
      highly metastatic subline of BALB/c mammary carcinoma (410.4) cells was shown to
      invade nearly three times as much as a low metastatic subline (168.1). Genistein,
      an inhibitor of tyrosine kinases, was found to inhibit invasion of 410.4 cells
      with an EC50 of approximately 1 microM. At a concentration of 37 microM, there
      was almost complete inhibition of invasion by genistein, whereas the structural
      analog, daidzein, which does not inhibit tyrosine kinases, had only a small
      effect. At higher concentrations (370 microM), daidzein also caused marked
      inhibition. Genistein was able to inhibit invasion at concentrations having
      little effect on cell growth. However, for daidzein, most of the effect on
      invasion was apparently due to its effect on growth inhibition. The relatively
      specific effect of genistein to inhibit tumor invasion suggests a role for
      tyrosine phosphorylation in this process. Genistein or other tyrosine kinase
      inhibitors may be effective inhibitors of tumor invasion and metastasis.

PMID- 7812936
TI  - Increased expression of gamma-glutamyl transpeptidase in transfected tumor cells
      and its relationship to drug sensitivity.
AB  - To test the hypothesis that elevated expression of the glutathione (GSH) salvage
      enzyme, gamma-glutamyl transpeptidase (gamma-GT) can confer resistance to
      chemotherapeutic agents, the cDNA for human gamma-GT was introduced into human
      prostate carcinoma cells by calcium phosphate precipitation. The sensitivity of a
      stable clone expressing an 18-fold increase in gamma-GT activity to melphalan (L
      PAM), cisplatinum and doxorubicin was compared to that of the parent cell line
      and a clone transfected with gamma-GT cDNA in the antisense orientation. Despite
      increased gamma-GT expression and the ability of intact cells to metabolize
      exogenous GSH, transfection did not result in increased intracellular GSH levels
      even when an exogenous source of GSH was provided. Furthermore, no change in
      sensitivity attributable to the transfection and increased expression of gamma-GT
      was detected with any of the three drugs. Our data indicate that an increase in
      gamma-GT expression, exceeding that typically associated with resistance
      phenotypes, is not sufficient to confer resistance to L-PMA, cisplatinum or
      doxorubicin in the absence of other alterations in GSH homeostasis.

PMID- 7812937
TI  - Carcinogens show comedogenic activity: a potential animal screen for tumorigenic
      substances.
AB  - Formation of a comedo, an impaction of horny cells in sebaceous follicles,
      entails a metaplastic change in the differentiation patterns of the follicular
      epithelium. Since metaplasia is a requisite early stage in carcinogenesis, we
      postulated that carcinogens might be comedogenic. The rabbit ear was used to
      assay the comedogenic potentialities of an array of known tumorigens. Complete
      carcinogens and some tumor promotors were invariably strongly comedogenic at
      concentrations of 1.0% and below. Comedogenic chemicals commonly found in skin
      care products usually required concentrations of 40% and greater to induce
      comedones which were small in comparison to carcinogen induced comedones. We
      suggest that the rabbit ear model might be an easy and reliable way to screen for
      carcinogenicity.

PMID- 7812938
TI  - The nature and expression of int-5, a novel MMTV integration locus gene in
      carcinogen-induced mammary tumors.
AB  - Our previous studies have resulted in the identification and cloning of int-5, a
      novel site of mouse mammary tumor virus (MMTV) integration, from BALB/c D2
      precancerous hyperplastic alveolar nodules (HAN). This paper presents a detailed
      characterization of the int-5 locus from both D2 HAN and normal genome and
      expression of the unique gene from the MMTV integration site. Our results show
      that the cellular gene at the MMTV integration site in the int-5 locus is
      identical to the gene encoding aromatase (CYP19), a member of the cytochrome P
      450 gene superfamily. MMTV is integrated within exon 10 in the 3' untranslated
      region of the aromatase gene. This gene (int-5/aromatase) is expressed in normal
      mammary gland and overexpressed in mammary tumors. These results suggest that the
      overexpression of this gene may be responsible for mammary tumorigenesis. This is
      the first demonstration of integration of MMTV in a cellular gene that plays a
      role in hormone-dependent breast cancers.

PMID- 7812939
TI  - Status of antioxidant systems in human carcinoma of uterine cervix.
AB  - Lipid peroxides, glutathione content and the activities of antioxidant enzymes
      were estimated in patients who had carcinoma of the uterine cervix, and the
      values were compared with those of normal. The results showed a remarkable
      reduction in glutathione content and in the activities of catalase and superoxide
      dismutase in neoplastic tissue in stages II, III and IV (P < 0.001) whereas the
      activities of glutathione peroxidase and glutathione reductase were significantly
      lower in stage III and IV patients than that of normal controls. The tissue level
      of lipid peroxides and the activity of glutathione-S-transferase were found to be
      significantly higher than that of normals from stage II onwards. These
      observations suggested the impaired antioxidant status in carcinoma of the
      uterine cervix.

PMID- 7812940
TI  - Detection of a novel lactate dehydrogenase isozyme and an apparent
      differentiation-associated shift in isozyme profile in hepatoma cell lines.
AB  - A hitherto unreported lactate dehydrogenase (LD) isoenzyme, which migrates
      electrophoretically to the relative position between LD2 and LD3 has been
      identified in the electropheratogram in 7 of 7 (100%) cultured hepatoma cell
      lines with various degrees of differentiation and is thus given the name LD2-3.
      LD2-3 seems to be specific for hepatoma cells because this atypical isoenzyme can
      not be detected in other tumor cell lines. In addition, the hepatoma cell lines
      also show a distinct pattern of LD isoenzyme and the isoenzyme pattern varies
      with the degree of differentiation. Hence, the expression pattern of LD isoenzyme
      phenotypes may provide a good marker for the investigation of human hepatoma cell
      differentiation.

PMID- 7812941
TI  - A precise, rapid and sensitive in vitro assay to measure the adhesion of ovarian
      tumour cells to peritoneal mesothelial cells.
AB  - Ovarian cancer is the second most common gynaecological cancer in the UK, causing
      2000 deaths per year. It spreads by shedding cells which attach to the
      mesothelial lining of the peritoneal cavity. In order to quantitatively study
      this interaction, a model system was developed in which mesothelial cells were
      cultured as monolayers in multiwell plates, and ovarian tumour cells were added
      that had been pre-labelled with a fluorescent dye (calcein). Synchronous
      interaction between the two populations was achieved by brief centrifugation at
      low g and the degree of attachment was measured on an automated fluorimeter after
      washing away the unbound cells. Using this procedure it was possible to measure
      tumour cell adhesion in 96 wells in 3-4 h. The reproducibility of the method was
      high even after short incubation times and the background absorbance was so low
      that the adhesion of less than a 1000 cells could be easily detected. The method
      works equally well for all ovarian tumour cell lines so far studied, and in
      preliminary experiments, it was shown that it can be used to screen for the
      effects of various blocking agents.

PMID- 7812942
TI  - Vitamin E acts as a useful chemopreventive agent to reduce spontaneous lung
      tumorigenesis in mice.
AB  - The present study was designed to evaluate whether vitamin E could be a useful
      chemopreventive agent to reduce spontaneous lung tumorigenesis in mice. Starting
      at 6 weeks of age, groups were divided into three groups, i.e. A/J mice fed a
      control diet (A/J control), A/J mice fed a vitamin E-supplemented diet (A/J
      vitamin E) and ddY mice fed a control diet (ddY control). At the 28th
      experimental week, nuclear NADPH-driven active oxygen generation, thiobarbituric
      acid reactive substances (TBARS) and DNA single strand breaks (DNA-SSB) in A/J
      mice fed a control diet were significantly higher than those in the ddY control
      group. A/J mice fed Vitamin E for 28 weeks could decrease the levels of TBARS and
      DNA-SSB with a significant difference, as compared with those in A/J control
      mice. The nuclear alpha-tocopherol levels in A/J controls were significantly
      lower than those in ddY controls, on the contrary, the vitamin feeding to A/J
      mice increased nuclear alpha-tocopherol levels more than that in the ddY
      controls. At the 40th experimental week, lung tumor incidence and tumor
      multiplicity (percentage of mice with tumors) in A/J controls were reduced and
      brought close to those in ddY control mice by vitamin E. Then the alpha
      tocopherol level in plasma of A/J controls was significantly lower than the level
      in plasma of ddY controls, and the level in tumor-bearing mice in A/J controls
      also showed a lower level with significant difference as compared to that in non
      tumor-bearing mice of A/J controls. These results suggest that the difference in
      susceptibility to spontaneous lung tumorigenesis between A/J and ddY mice partly
      depends on the difference of oxidative stress on the pulmonary nuclei, and
      vitamin E can act as a useful chemopreventive agent to reduce spontaneous lung
      tumorigenesis in mice.

PMID- 7812943
TI  - Long-term persistence and cytokinetics of human tumor cells in vitro following
      high-dose alkylating agent exposure.
AB  - Relapse after high-dose alkylating agent therapy continues to be an important
      clinical issue. To begin to understand the characteristics of cells surviving
      alkylating agent exposure human MCF-7 breast carcinoma cells were exposed to a
      range of concentrations of melphalan or cis-diamminedichloroplatinum(II) and cell
      survival determined by colony formation over a time course of 4 weeks. When
      antitumor alkylating agent exposure killed 3-4 logs of cells as determined by
      surviving fraction after 1 week of colony formation a progressive increase in
      surviving fraction was evident over the 4-week course of the experiment. Many
      attached single cells with abnormal morphology were evident in these dishes;
      however, the colonies which arose over the 4-week observation time were made up
      of cells morphologically indistinguishable from the control cells. Cell cycle
      patterns in the cultures exposed to high concentrations of the antitumor
      alkylating agents indicated a block in G2/M but by 4 weeks post-drug exposure
      most had returned to a normal exponential growth pattern. When MCF-7 cells or
      human SW2 small cell lung cancer cells were exposed to a concentration of
      melphalan or cis-diamminedichloroplatinum(II) that killed 1-2 logs of cells
      followed by exposure to a concentration range of the same drug for 24 h or 7 days
      later resistance to the second drug exposure was evident in both cell lines.
      Using [14C]melphalan the uptake of the drug into MCF-7 cells pre-treated was
      compared. Decreased drug uptake did not appear to be a factor in resistance to
      melphalan observed upon re-exposure to the drug. The potential clinical
      implications of these findings is discussed.

PMID- 7812944
TI  - Increased 8-hydroxydeoxyguanosine in hepatic DNA of rats treated with the
      peroxisome proliferators ciprofibrate and perfluorodecanoic acid.
AB  - In this study we examined the ability of peroxisome proliferators to induce
      oxidative DNA damage in the form of 8-hydroxydeoxyguanosine (OHdG). We studied
      the hypolipidemic drug ciprofibrate, which is among the most potent and
      efficacious of the peroxisome proliferators, and perfluorodecanoic acid (PFDA),
      which is an inhibitor of peroxisomal beta-oxidation. Rats were fed 0.01%
      ciprofibrate in the diet, or were injected with PFDA at doses of 3 or 10 mg/kg
      every 14 days (controls and ciprofibrate-fed rats were given equivalent doses of
      corn oil). Rats were maintained for 10 days, 24 days, 6 weeks, 26 weeks, or 54
      weeks. DNA was isolated from the liver at these times and hydrolysed to
      nucleosides, and the levels of OHdG as well as normal nucleosides were analysed
      by high-performance liquid chromatography with electrochemical detection.
      Ciprofibrate increased OHdG concentrations at all times except for the initial 10
      day timepoint. Both doses of PFDA increased OHdG levels at all times except the
      last timepoint, at which only the higher dose produced a significant increase.
      This study shows that both ciprofibrate and PFDA induce oxidative DNA damage in
      the form of OHdG. Furthermore, the inhibition of peroxisomal beta-oxidation by
      PFDA does not affect the development of OHdG.

PMID- 7812945
TI  - Human tumor gangliosides inhibit murine immune responses in vivo.
AB  - Gangliosides which are shed by tumor cells clearly inhibit cellular immune
      responses in vitro. However, the immunosuppressive activity of these molecules
      have been more difficult to ascertain in vivo. Here we have adapted a murine
      model to determine the effects of tumor gangliosides in an in vivo
      microenvironment, the lymph node draining the site of stimulation by allogeneic
      cells. In this model, allogeneic splenocytes (BALB/c) are s.c. injected into C3H
      mice. The cellular immune response in the draining popliteal lymph nodes 4 days
      later is evidenced as an increase in lymph node mass (2-fold), lymphocyte number
      (6-fold), and lymphocyte DNA synthesis (6-fold). Purified human neuroblastoma
      gangliosides (10 nmol) coinjected with the stimulating allogeneic cells
      significantly suppressed this in vivo immune response. The increase in the lymph
      node mass was reduced by 65% (0.66 versus 1.89 mg), the increase in lymphocyte
      number (4.0 x 10(6) cells/node) was almost completely inhibited (1.1 x 10(6)
      cells/node), and in vitro [3H]thymidine uptake by the lymphocytes recovered in
      vivo was reduced by 80%. In contrast to the inhibition by tumor gangliosides,
      liposomes of cholesterol:lecithin were not inhibitory. Thus, tumor gangliosides,
      specifically, modulate cellular immune responses in vivo, which may contribute to
      the observed enhancement of tumor formation by these molecules.

PMID- 7812946
TI  - Clonal expansion and attenuated apoptosis in Wilms' tumors are associated with
      p53 gene mutations.
AB  - The p53 gene product is required for activation of an apoptotic pathway triggered
      by oncogenes and cytotoxic agents. Wilms' tumor, a pediatric renal malignancy,
      provides a paradigm for evaluating genetic events involved in tumor progression.
      This malignancy is generally not associated with p53 mutations, and even in
      advanced disease states is quite responsive to current treatment regimens. The
      anaplastic histological variant of Wilms' tumor, however, is frequently
      associated with p53 gene mutations and shows poor prognosis. We analyzed seven
      Wilms' tumors for which we had paired samples from nonanaplastic and anaplastic
      regions. p53 mutations were detected in six of these tumors, five of which
      demonstrated mutations restricted to anaplastic regions. Nonanaplastic cells of
      the sixth sample were heterozygous for a p53 mutation, whereas the anaplastic
      area of this tumor showed reduction to homozygosity. These results indicate that
      progression to anaplasia is associated with clonal expansion of cells which have
      acquired a p53 mutation. We demonstrated that tumor cells with p53 mutations show
      attenuated apoptosis, suggesting that such lesions may provide a selective
      advantage in vivo by decreasing cell death.

PMID- 7812947
TI  - Tumor progression and loss of heterozygosity at 5q and 18q in non-small cell lung
      cancer.
AB  - We investigated the frequency and clinical significance of loss of heterozygosity
      (LOH) at the APC, MCC, and DCC tumor suppressor gene loci in 108 cases of
      resected non-small cell lung cancer (NSCLC). LOH at the APC/MCC gene cluster at
      chromosome 5q21 occurred frequently; it affected 29% of informative NSCLC cases
      and correlated with a significantly worse survival (P < 0.01). Furthermore, in
      the subtype most frequently affected (SCC), LOH at 5q not only correlated with a
      worse survival but also tumor involvement of the mediastinal and/or hilar nodes.
      In contrast, LOH at the DCC locus at chromosome 18q was far less frequent,
      occurring in 14% of NSCLC cases, and it was not associated with advanced stage or
      prognosis. These data suggest that LOH at 5q has a role in determining tumor
      progression and survival in NSCLC, and may prove to be a clinically useful
      prognostic indicator.

PMID- 7812949
TI  - Unscheduled activation of cyclin B1/Cdc2 kinase in human promyelocytic leukemia
      cell line HL60 cells undergoing apoptosis induced by DNA damage.
AB  - We have studied changes in cyclin A- and B1-dependent kinases during apoptosis
      induced in human promyelocytic leukemia (HL60) cells treated with the
      topoisomerase I inhibitor camptothecin. We found that cyclin B1/Cdc2 kinase
      activity transiently increases within 30 min after camptothecin treatment. This
      increase is followed by a rapid inactivation of the cyclin B1/Cdc2 kinase that is
      associated with Cdc2 tyrosine phosphorylation without any change in Cdc2 or
      cyclin B1 protein levels. The DNA polymerase inhibitor aphidicolin abrogates
      camptothecin-induced changes in cyclin B1/Cdc2 kinase activity, indicating that
      DNA replication-induced DNA damage is essential for both Cdc2 alterations and
      apoptosis activation. Apoptosis and the initial cyclin B1/Cdc2 kinase activation
      were amplified using synchronized S-phase cells, and cyclin A/cdk2 kinase did not
      change under these conditions. The same transient activation and subsequent
      inactivation of cyclin B1/Cdc2 kinase were observed after DNA damage by etoposide
      or bis-(2-chloroethyl)methylamine hydrochloride. These observations suggest that
      DNA damage promotes the transient and unscheduled stimulation of cyclin B1/Cdc2
      kinase activity in HL60 cells prior to apoptosis.

PMID- 7812948
TI  - Localization of tumor suppressor loci on chromosome 9 in primary human renal cell
      carcinomas.
AB  - To investigate the potential loss of tumor suppressor gene loci on chromosome 9
      in human renal cell tumorigenesis we analyzed 42 paired normal and tumor DNAs
      with 18 polymorphic microsatellite markers spanning this chromosome. Fourteen of
      42 (33%) tumors showed partial or complete deletion of chromosome 9. Deletion
      mapping provided evidence for the presence of a suppressor locus on both the
      short and long arm of chromosome 9. Homozygous deletion at 9p21-22 in one renal
      tumor and a selective deletion of distal 9q in another tumor localized the
      critical regions. The CDKN2/p16 gene was further investigated as a candidate
      suppressor locus on 9p21-22 by multiplex PCR, Southern analysis, and exon
      sequencing. We found no additional cases of homozygous deletion nor any
      rearrangements or point mutations of CDKN2/p16. This is the first report of 9p
      loss of heterozygosity, homozygous deletion of 9p21-22 and selective deletion of
      9q in primary renal cell carcinomas. Understanding the molecular genetic basis of
      renal cell progression will require the isolation and characterization of
      additional tumor suppressor genes on chromosome 9.

PMID- 7812950
TI  - Enhanced efficacy of combinations of retinoic acid- and retinoid X receptor
      selective retinoids and alpha-interferon in inhibition of cervical carcinoma cell
      proliferation.
AB  - Retinoic acid receptors and retinoid X receptors form heterodimers, bind to
      retinoic acid response elements, and transactivate the transcription of retinoid
      responsive genes. Two synthetic retinoids [4-(5,6,7,8-tetrahydro-5,5,8,8
      tetramethyl-2-anthracenyl)benzoic acid (TTAB) and 6-(5,6,7,8-tetrahydro-5,5,8,8
      tetramethyl-2-naphthalenyl)-2-naphthale n ecarboxylic acid (TTNN)], which
      preferentially bind retinoic acid receptors, inhibited the proliferation of
      cervical carcinoma ME180 cells by 50% at 0.2 nM and 0.2 microM, respectively. In
      contrast, two other retinoids [2-(4-carboxyphenyl)-2-(5,6,7,8-tetrahydro-5,5,8,8
      tetramethyl-2- naphthalenyl)-1,3-dithiane (SR11203) and 4-(2-methyl-1-(5,6,7,8
      tetrahydro-5,5,8,8-tetramethyl-2- naphthalenyl)propenyl)benzoic acid (SR11217)],
      which preferentially bind retinoic X receptors, inhibited growth by only 12 and
      18% at 1 microM, respectively. The combination of suboptimal concentrations of
      TTAB (0.1 nM) or TTNN (10 nM) with each of the retinoic X receptor-selective
      retinoids at 1 microM showed more than additive effects on cell proliferation,
      especially with SR11217. Further increases in proliferation inhibition were
      observed when IFN-alpha (100 units/ml) was added to these retinoid combinations.
      Activation of transcription of a reporter gene linked 3' to the retinoic acid
      receptor beta retinoic acid response element in transiently transfected cells
      also exhibited additive effects when the cells were treated with combinations of
      TTAB or TTNN with SR11217. This additive activation of transcription may be the
      reason why the combination of retinoids is more effective than each retinoid
      alone. The results also suggest that the use of combinations of retinoids and IFN
      alpha may lead to enhanced antitumor effects.

PMID- 7812951
TI  - bcl-2 and p53 oncoprotein expression during colorectal tumorigenesis.
AB  - Apoptosis or programmed cell death represents a mechanism by which cells
      possessing DNA damage can be deleted. The bcl-2 proto-oncogene is a known
      inhibitor of apoptosis that may allow the accumulation and propagation of cells
      containing genetic alterations. To determine if and when the bcl-2 gene is
      activated during colorectal tumorigenesis and its relationship to p53, we
      analyzed normal mucosa, hyperplastic and dysplastic epithelial polyps, and
      carcinomas for the expression of these markers using immunohistochemistry.
      Whereas bcl-2 staining was restricted to basal epithelial cells in normal and
      hyperplastic mucosa, bcl-2 expression was detected in parabasal and superficial
      regions in dysplastic polyps and carcinomas. An inverse correlation was found
      between bcl-2 and p53 expression in adenomas, suggesting that these markers may
      regulate a common cell death pathway. Furthermore, carcinomas with a high
      percentage of bcl-2-positive cells were significantly more likely to have low
      rates of spontaneous apoptosis, as determined histologically, than those cancers
      with low or absent bcl-2 expression. Abnormal activation of the bcl-2 gene
      appears to be an early event in colorectal tumorigenesis that can inhibit
      apoptosis in vivo and may facilitate tumor progression.

PMID- 7812953
TI  - The insulin-like growth factor I receptor: a key to tumor growth?
AB  - The insulin-like growth factor I receptor (IGF-IR) belongs to the family of
      transmembrane tyrosine kinase receptors, like the receptors for platelet-derived
      growth factor, the epidermal growth factor, insulin, and others. Genetic evidence
      has shown that the IGF-IR is required for optimal growth in vitro and in vivo.
      Even more important, however, have been recent findings from several laboratories
      clearly showing that the IGF-IR is an absolute requirement for the establishment
      and maintenance of the transformed phenotype, both in vivo and in vitro and in
      several cell types. These findings indicate that the IGF-IR plays a central role
      in the mechanism of transformation and, as such, could be a preferred target for
      therapeutic interventions.

PMID- 7812952
TI  - Structure of the human MLH1 locus and analysis of a large hereditary nonpolyposis
      colorectal carcinoma kindred for mlh1 mutations.
AB  - Hereditary nonpolyposis colorectal carcinoma is a major cancer susceptibility
      syndrome known to be caused by inheritance of mutations in at least four genes
      such as hMSH2, hMLH1, hPMS1, and hPMS2 which encode components of a DNA mismatch
      repair system. The hMLH1 genomic locus on chromosome 3p has been cloned and shown
      to cover approximately 58 kilobases of genomic DNA and contain 19 exons. The
      sequence of all of the intron-exon junctions has been determined and used to
      develop methods for analyzing each hMLH1 exon for mutations. Using these methods
      to analyze a 3p-linked hereditary nonpolyposis colorectal carcinoma kindred, we
      have demonstrated that cancer susceptibility in this family is due to the
      inheritance of a frame shift mutation in the hMLH1 gene.

PMID- 7812954
TI  - Fibers released from cigarette filters: an additional health risk to the smoker?
AB  - Tests of 12 popular brands of cigarettes manufactured by 6 companies from the
      United States have shown that fibers were released from the filters and that
      there exists probable cause to suggest that fibers are inhaled and/or ingested.
      Filter fibers, made of cellulose acetate, were implanted in mice for 6 months.
      The fibers withstood degradation and retained the tobacco-brown color and bright
      fluorescence of the tobacco tar that had been adsorbed from cigarette smoke. With
      a confocal laser scanning microscope, we have observed cigarette filter fibers in
      lung tissue from patients with lung cancer and who were known to be habitual
      smokers. These findings raise the question as to whether fibers released from
      cigarettes further jeopardize the health of smokers and document the need to test
      components of cigarette filters for toxicity and tumorigenicity.

PMID- 7812955
TI  - Chemoprevention of colon carcinogenesis by dietary curcumin, a naturally
      occurring plant phenolic compound.
AB  - Human epidemiological and laboratory animal model studies have suggested that
      nonsteroidal antiinflammatory drugs reduce the risk of development of colon
      cancer and that the inhibition of colon carcinogenesis is mediated through the
      alteration in cyclooxygenase metabolism of arachidonic acid. Curcumin, which is a
      naturally occurring compound, is present in turmeric, possesses both
      antiinflammatory and antioxidant properties, and has been tested for its
      chemopreventive properties in skin and forestomach carcinogenesis. The present
      study was designed to investigate the chemopreventive action of dietary curcumin
      on azoxymethane-induced colon carcinogenesis and also the modulating effect of
      this agent on the colonic mucosal and tumor phospholipase A2, phospholipase C
      gamma 1, lipoxygenase, and cyclooxygenase activities in male F344 rats. At 5
      weeks of age, groups of animals were fed the control (modified AIN-76A) diet or a
      diet containing 2000 ppm of curcumin. At 7 weeks of age, all animals, except
      those in the vehicle (normal saline)-treated groups, were given two weekly s.c.
      injections of azoxymethane at a dose rate of 15 mg/kg body weight. All groups
      were continued on their respective dietary regimen until the termination of the
      experiment at 52 weeks after the carcinogen treatment. Colonic tumors were
      evaluated histopathologically. Colonic mucosa and tumors were analyzed for
      phospholipase A2, phospholipase C gamma 1, ex vivo prostaglandin (PG) E2,
      cyclooxygenase, and lipoxygenase activities. The results indicate that dietary
      administration of curcumin significantly inhibited incidence of colon
      adenocarcinomas (P < 0.004) and the multiplicity of invasive (P < 0.015),
      noninvasive (P < 0.01), and total (invasive plus noninvasive) adenocarcinomas (P
      < 0.001). Dietary curcumin also significantly suppressed the colon tumor volume
      by > 57% compared to the control diet. Animals fed the curcumin diet showed
      decreased activities of colonic mucosal and tumor phospholipase A2 (50%) and
      phospholipase C gamma 1 (40%) and levels of PGE2 (> 38%). The formation of
      prostaglandins such as PGE2, PGF2 alpha, PGD2, 6-keto PGF1 alpha, and thromboxane
      B2 through the cyclooxygenase system and production of 5(S)-, 8(S)-, 12(S)-, and
      15(S)-hydroxyeicosatetraenoic acids via the lipoxygenase pathway from arachidonic
      acid were reduced in colonic mucosa and tumors of animals fed the curcumin diet
      as compared to control diet. Although the precise mechanism by which curcumin
      inhibits colon tumorigenesis remains to be elucidated, it is likely that the
      chemopreventive action, at least in part, may be related to the modulation of
      arachidonic acid metabolism.

PMID- 7812956
TI  - Correlation of the in situ detection of polymerase chain reaction-amplified
      metalloproteinase complementary DNAs and their inhibitors with prognosis in
      cervical carcinoma.
AB  - The purpose of this study was to correlate the presence of matrix
      metalloproteinase (MMP)-9 and MMP-2 and tissue inhibitors of metalloproteinase
      (TIMP)-1 and TIMP-2 mRNAs, detected in serial sections using the reverse
      transcriptase in situ PCR technique, with prognosis in 23 cases of cervical
      carcinoma. PCR-amplified MMP and TIMP cDNA were restricted to the invasive
      cancers cells and the surrounding stromal cells. The ratios of cancer and stromal
      cells expressing MMP-9 and MMP-2 to those expressing TIMP-1 and TIMP-2 were
      approximately 1 in those cancers with a good prognosis. This MMP:TIMP ratio in
      the cancer and stromal cells with a poor prognosis was significantly increased to
      5.4 and 3.4 (P < 0.0001), respectively, reflecting a marked reduction in the TIMP
      detection rate in cancers with a poor prognosis. In cervical cancer cell lines
      SiHa and HeLa, the MMP:TIMP ratio was also close to 1 and, interestingly, these
      cell lines are invasive but rarely metastatic in nude mice. These data suggest
      that the balance of MMP-9 and MMP-2 to TIMP-1 and TIMP-2 expression is an
      essential factor in the aggressiveness of cervical cancer.

PMID- 7812957
TI  - Cholecystokinin-B/gastrin receptor: a novel molecular probe for human small cell
      lung cancer.
AB  - The brain-gut hormones, gastrin and cholecystokinin, have a trophic effect on the
      gastrointestinal mucosa in vivo and promote the growth of several neoplastic cell
      lines. In this study, cholecystokinin-B/gastrin receptor has been demonstrated to
      provide a novel molecular marker for the diagnosis of small cell lung cancer by
      using biopsy specimens. Physiological expression of the receptor mRNA is
      detectable in particular areas of the human brain, stomach, and pancreas but not
      in the lung. The receptor mRNA was detected selectively in all small cell lung
      cancer (10 cases) with a RT-PCR assay. By contrast, it was detectable in only 1
      of 13 squamous cell carcinomas or 21 adenocarcinomas of the lung. Thus, the
      cholecystokinin-B/gastrin receptor could be an attractive therapeutic target for
      small cell lung cancer.

PMID- 7812959
TI  - Exon 5 deletion variant estrogen receptor messenger RNA expression in relation to
      tamoxifen resistance and progesterone receptor/pS2 status in human breast cancer.
AB  - The exon 5 deletion splice variant of estrogen receptor (delta 5 ER), which in
      vitro is constitutively active in the absence of estrogens, may have a role in
      conferring both tamoxifen resistance and ER-related phenotype in breast cancer.
      We have investigated the expression of this variant in vivo (at the level of
      mRNA) in relation to known tamoxifen resistance and expression of the estrogen
      regulated genes progesterone receptor (PgR) and pS2. The amount of delta 5 ER
      mRNA relative to wild type (WT) ER mRNA (% delta 5/WT) was assayed in 70
      tamoxifen-resistant and 50 primary breast carcinomas using reverse
      transcription/PCR. Both WT and delta 5 ER mRNA were detected in the majority of
      tumors, although delta 5 ER was detected only in the presence of WT ER. Overall
      no significant difference was seen in % delta 5/WT ER between tamoxifen-resistant
      and primary control tumors (medians, 13 and 15%, respectively). Tumors in both
      control and resistant groups which expressed PgR/pS2 in the absence of measurable
      ER protein (ER- PgR+ and ER- pS2+) had significantly higher delta 5 ER mRNA
      levels compared with other phenotypes (P < 0.002). This association with ER-/pS2+
      tumors has not been demonstrated previously. In ER+ tumors which expressed pS2,
      significantly greater delta 5 ER mRNA expression was observed in tamoxifen
      resistant compared with control tumors (P = 0.05). A similar although
      nonsignificant trend was observed in ER+ PgR+ tumors. While delta 5 ER mRNA is
      unlikely to be responsible for tamoxifen resistance in most breast cancers,
      elevated delta 5 ER mRNA levels may be important in some tumors, especially those
      which continue to express high levels of PgR/pS2.

PMID- 7812958
TI  - Characterization of bombesin/gastrin-releasing peptide receptors in human breast
      cancer and their relationship to steroid receptor expression.
AB  - Bombesin (BN) and its mammalian counterpart, gastrin-releasing peptide (GRP), are
      hormonally active peptides which appear to function as autocrine or paracrine
      growth factors in a variety of cells. As part of a long-term investigation of the
      relationship of peptide and steroid hormone receptors to breast cancer
      progression and treatment, we examined the binding of [125I-Tyr4]BN to membranes
      isolated from 100 human breast carcinomas. Thirty-three of these tumors expressed
      BN/GRP receptor levels of > 10 fmol/mg membrane protein. Two classes of [Tyr4]BN
      binding sites were detected using Scatchard analyses of radioligand association
      data from hormone displacement curves. The high-affinity binding sites exhibited
      a mean dissociation constant (Kd1) of 2.1 nM and a mean specific binding capacity
      (Bmax1) of 237 fmol/mg membrane protein. The low affinity binding sites had a
      mean dissociation constant (Kd2) of 0.3 microM and a mean binding capacity
      (Bmax2) of 5.9 pmol/mg membrane protein. BN/GRP receptor expression in a breast
      carcinoma was unrelated to patient age. When the levels of BN/GRP receptors were
      compared to the content of the sex steroid receptors, a highly significant
      positive correlation (P < 0.005) was observed between the binding capacities of
      high-affinity [Tyr4]BN-binding sites and estrogen receptor levels and between the
      concentrations of low affinity [Tyr4]BN-binding sites and progestin receptor
      levels (P < 0.05). This represents the first report of these labile, regulatory
      proteins in biopsies of human breast carcinomas. Expression of specific receptor
      proteins for BN/GRP, potent mitogens, in a large number of human breast cancers
      suggests that they may be involved in tumor cell progression. The approach based
      on determination of BN/GRP receptors might be useful to guide a hormonal therapy
      with BN/GRP antagonists in some women with breast cancer.

PMID- 7812960
TI  - Antiepileptic treatment and risk for hepatobiliary cancer and malignant lymphoma.
AB  - The possible influence of phenobarbital and phenytoin treatment on cancer risk
      was investigated in a case-control study nested in a cohort of 8004 epileptic
      patients in Denmark. Information on anticonvulsive treatments was abstracted for
      95% of 60 patients with cancers of the liver and biliary tract or malignant
      lymphoma and for 94% of 171 cancer-free control patients. Use of anticonvulsive
      drugs was correlated with angiographic procedures that used Thorotrast, a well
      known human liver carcinogen. After exclusion of study subjects exposed to
      Thorotrast, no association was seen between treatment with phenobarbital and
      cancer of the liver (odds ratio, 1.0; 95% confidence interval, 0.1-8.0) or
      biliary tract (odds ratio, 0.8; 95% confidence interval, 0.1-4.2). Furthermore, a
      histopathological evaluation of slides from 7 of 9 liver cancer patients not
      treated with Thorotrast revealed that 3 of the 4 cases of hepatocellular
      carcinoma involved cirrhosis of the liver, which suggested an etiological role
      for alcohol or viral hepatitis. A possible link was observed between use of
      phenytoin and risk for non-Hodgkin's lymphoma (1.8; 0.5-6.6), with a rising trend
      in risk with increasing dose. Our results suggest that the increased risk for
      cancers of the liver and biliary tract among Danish epileptic patients is likely
      to be due to Thorotrast administration and factors associated with cirrhosis of
      the liver rather than to anticonvulsive treatment.

PMID- 7812961
TI  - Basic fibroblast growth factor does not protect against classical radiation
      pneumonitis in two strains of mice.
AB  - Basic fibroblast growth factor recently has been reported to confer significant
      protection against death from radiation pneumonitis in C3H/HeJ mice. Although the
      mechanism of this protection remains unknown, one hypothesis, based on in vitro
      data, is that basic fibroblast growth factor protects against radiation-induced
      apoptosis in pulmonary endothelial cells. Because of the potential clinical
      importance of these data, we repeated our experiments in two strains of mice with
      differing sensitivities to radiation pneumonitis. One mouse strain, C3Hf/Kam,
      originated from the same C3H/He strain as the C3H/HeJ mouse used by Fuks et al.
      in their 1994 study. The other strain, the NCR/Sed-nu/+ strain, is a white mouse
      heterozygous for the nude trait. In our laboratory, the LD50 for radiation
      pneumonitis between 12 and 28 weeks after irradiation, the standard assay time
      for this phase of radiation-induced lung damage, is 12.5 Gy in the C3Hf/Kam and
      8.5 Gy in the NCR/Sed-nu/+ strain. Contrary to previous results in the
      literature, we found that basic fibroblast growth factor did not protect against
      radiation pneumonitis in either C3Hf/Kam or NCR/Sed-nu/+ mice. Quantitation of
      apoptosis after both doses to the lungs of the two strains showed that the
      incidence of apoptosis was less than 1% in C3Hf/Kam mice and 0.5% in NCR/Sed-nu/+
      mice. These apoptotic bodies were scattered throughout the lung and were not
      located selectively in endothelial cells of any size blood vessels.

PMID- 7812962
TI  - Insulin-like growth factor I (IGF-I) and the IGF-I receptor prevent etoposide
      induced apoptosis.
AB  - The interaction of insulin-like growth factors (IGF) with the IGF-I receptor
      promotes cell proliferation and survival. We examined the role of the IGF-I
      receptor as a possible direct inhibitor of apoptosis induced by the topoisomerase
      I inhibitor etoposide. When exposed to this agent, BALB/c 3T3 cells that
      constitutively overexpress the human IGF-I receptor (p6 cells) arrested in S
      phase and subsequently underwent apoptosis as determined by the appearance of a
      pre-G1 apoptotic peak when studied by flow cytometry and the characteristic
      internucleosomal fragmentation of DNA. The addition of IGF-I markedly inhibited
      etoposide-induced apoptosis in a concentration-dependent manner. IGF-I was not
      mitogenic in the presence of etoposide. IGF-I was less effective in preventing
      apoptosis in parental BALB/c 3T3 cells and had no effect on etoposide-induced
      cell killing of mouse embryo fibroblasts that have a targeted disruption of the
      IGF-I receptor gene. These results demonstrate an important role for the IGF-I
      receptor as an inhibitor of apoptosis, independent of its mitogenic actions.

PMID- 7812963
TI  - Normocalcemic effect of gallium nitrate in a hypercalcemic rat model.
AB  - An established rat hypercalcemia model was used to study the effects of gallium
      nitrate on elevated serum calcium levels. Gallium nitrate was administered by
      i.v. or i.p. injection at daily doses of 0.07-0.45 mmol/kg for 5 days to the
      hypercalcemic rats beginning 1 day following surgery. A dose-correlated
      normocalcemic response was observed. Gallium nitrate administered late after the
      induction of the hypercalcemic state was also effective in reducing serum calcium
      levels. The p.o. administration, however, even at doses as high as 0.45 mmol/kg,
      did not reduce serum calcium to normal levels. The values of area under the
      concentration versus time curve (0-24 h) of gallium in normal rats were
      comparable after i.v. [49.2 (micrograms/ml)h] or i.p. [57.0 (micrograms/ml)h]
      injections. In contrast, the p.o. route achieved only 15% bioavailability, which
      may explain the ineffectiveness of p.o. administered gallium nitrate at that dose
      level. This study suggests that daily i.v. bolus injections of gallium nitrate
      for managing hypercalcemia may be potentially as effective as the current regimen
      of continuous i.v. infusion.

PMID- 7812964
TI  - Change of the sequence specificity of daunorubicin-stimulated topoisomerase II
      DNA cleavage by epimerization of the amino group of the sugar moiety.
AB  - Antitumor drugs stimulate topoisomerase II-mediated DNA cleavage in a DNA
      sequence-specific manner. The drug sequence specificity is often very similar
      among antitumor agents of the same chemical class. In this work, we demonstrate,
      however, that 3'-epidaunorubicin has a markedly different sequence specificity as
      compared with the parent drugs daunorubicin and doxorubicin. The analogue
      stimulates distinct cleavage intensity patterns in agarose and sequencing gels
      with two different DNA substrates, although its cleaving activity was lower than
      that of daunorubicin. A statistical analysis of 44 sites specifically stimulated
      by the analogue showed that a major difference between the analogue and parent
      drugs was at position -2, where a guanine is highly preferred by the analogue,
      whereas parent drugs prefer a thymine and exclude instead a guanine.
      Interestingly, an analogue with no substituents at the 3'-C of the sugar was able
      to stimulate DNA cleavage at sites stimulated by parent drugs as well as at those
      stimulated by 3'-epidaunorubicin. In contrast, the presence of a 2'-OH or a 3'
      epi-OH in the sugar moiety and the removal of the OH at 9-C of the A ring did not
      alter the drug site selectivity, in agreement with several other modifications
      studied previously. DNA binding affinities of studied agents were not related to
      drug sequence specificity. The data demonstrate a critical role of the 3'
      position for optimal anthracycline interactions in the ternary complex. The
      findings, for the first time, establish a clear relationship between a specific
      drug substituent and base sequence selectivity and indicate putative DNA- and
      enzyme-interacting domains of the anthracycline molecule.

PMID- 7812965
TI  - Rapid and specific uptake of anti-Tac disulfide-stabilized Fv by interleukin-2
      receptor-bearing tumors.
AB  - The disulfide-stabilized Fv (dsFv) is a novel form of a variable-region fragment
      (Fv) of an antibody which is stabilized by an interchain disulfide bond. As a
      consequence, it is more stable than its Fv analogue. Anti-Tac(dsFv) is derived
      from anti-Tac(IgG) which specifically binds to the p55 subunit of the interleukin
      2 receptor (IL2R alpha). The receptor is found in large numbers on activated T
      cells and many T-cell leukemias. The biodistribution patterns of 125I-anti
      Tac(dsFv) and 125I-anti-Tac(IgG) were determined in athymic nude mice bearing two
      s.c. tumors, one expressing a stably transfected plasmid encoding IL2R alpha
      (ATAC4) and one composed of parental untransfected A431 epidermoid carcinoma
      cells. Anti-Tac(dsFv), which has a molecular weight of 25,000, was specifically
      captured by the ATAC4 tumors but not by control A431 tumors. The antigen-specific
      tumors accumulated > 2% of the injected dose/g within 15-45 min after i.v.
      injection. The level of radioactivity in the ATAC4 tumors was maintained at > 1%
      of the injected dose/g for nearly 6 h, at which time the ATAC4 tumors contained
      11-fold more 125I-anti-Tac(dsFv) than did the A431 tumors. Unbound 125I-anti
      Tac(dsFv) was rapidly cleared from the blood with apparently biphasic
      pharmacokinetics (alpha t 1/2 = < 10 min; beta t 1/2 = approximately 5.5 h).
      Initially, the bulk of the 125I-anti-Tac(dsFv) appeared in the kidneys. In
      contrast, 125I-anti-Tac(IgG) showed no tumor- or tissue-specific uptake over the
      24-h time course of the experiments and remained primarily in the blood stream
      (blood clearance t 1/2 = approximately 12 h). This is the first report of the
      biodistribution of a dsFv fragment. Because of its rapid uptake by IL2 receptor
      bearing tumors, short serum half-life, and increased stability, radiolabeled anti
      Tac(dsFv) may be useful for the imaging and therapy of neoplasias expressing the
      IL2 receptor.

PMID- 7812966
TI  - NAD(P)H:quinone oxidoreductase expression and mitomycin C resistance developed by
      human colon cancer HCT 116 cells.
AB  - An association between the resistance to mitomycin C (MMC) and a decrease of
      NAD(P)H:quinone oxidoreductase (NQO1) activity was reported for a MMC-resistant
      subline, HCT 116-R30A, derived from MMC-sensitive HCT 116 cells. Eight NQO1 cDNA
      clones were isolated from these two sublines by reverse transcription-PCR. Two
      clones, pDT9 from HCT 116 and pDT20 from HCT 116-R30A, are the full length of 274
      amino acids. These two clones differ by a T to C substitution at nucleotide 464,
      which results in a replacement of arginine 139 by tryptophan in the enzyme. NQO1
      of pDT9 and pDT20 was expressed in Escherichia coli, purified, and shown to have
      a protein subunit of M(r) 30,000. The change of amino acid 139 resulted in a
      shift of isoelectric pH from 9.5 to 8.35 and a 60% decrease of activity in
      reducing MMC. All of the other six clones differ from pDT9 by a deletion of exon
      4. On Northern blot, we detected two mRNA species of NQO1 (1.2 and 2.7 kilobases)
      due to alternative polyadenylation in all sublines. MMC-resistant sublines showed
      75-90% mRNA expression relative to HCT 116 cells. Reverse transcription-PCR
      amplification of cDNA fragment of nucleotide 298-617 revealed two full-length
      mRNAs in HCT 116 cells but only one full-length mRNA in HCT 116-R30A cells. An
      exon 4 deletion mRNA was detected in both sublines. The two full-length mRNAs may
      be from either alleles or chimeras of the same gene and the exon 4 deletion mRNA
      is a result of alternative splicing. On Western blot, we detected only one M(r)
      30,000 protein in all sublines. A substantial decrease of this protein in MMC
      resistant sublines (5% of HCT 116) explained the 95% decrease of their NQO1
      activity. Transcriptional regulation and posttranscriptional modification may be
      responsible for the disparity of gene expression of NQO1 and the low
      concentration of NQO1 protein in MMC-resistant sublines. Reversal of MMC
      resistance and the recovery of NQO1 in two revertants further supports the
      hypothesis that cellular control of NQO1 can modulate the cytotoxicity of MMC.

PMID- 7812967
TI  - Splice site mutation in the glucocorticoid receptor gene causes resistance to
      glucocorticoid-induced apoptosis in a human acute leukemic cell line.
AB  - Induction of apoptosis is the molecular basis for the therapeutic application of
      glucocorticoids (GC) in human leukemia. The beneficial effect of endocrine
      therapy is, however, hampered by the occurrence of resistant clones evolving
      under selective GC pressure. To delineate molecular mechanisms of GC resistance,
      we PCR amplified, cloned, and sequenced GC receptor (GR) transcripts and gene
      segments from a GC-resistant subclone of the human acute leukemic cell line CCRF
      CEM, termed CEM-R6. Our analyses revealed that one GR gene allele harbored a
      point mutation (L753F) previously shown to compromise GR functions in other CCRF
      CEM derivatives. On the second allele, we identified an A to G point mutation in
      the 3'-splice junction of intron G. As a consequence, a cryptic splice site 8
      base pairs downstream within exon 8 is recognized, which leads to an 8-base
      deletion in the GR mRNA, resulting in reading frame shift and 2 consecutive in
      frame preterminal stop codons. Translation of this mutant mRNA would produce a
      truncated GR protein missing 93 amino acids of the ligand-binding domain and
      expressing 9 altered residues at its new COOH terminus. In concert with the L753F
      mutation on the other allele, this molecular defect explains the GC-resistant
      phenotype and provides further evidence for mutational GR gene inactivation as a
      mechanism for human leukemic cells to escape GC-induced apoptosis.

PMID- 7812968
TI  - bcl-2 deficiency in mice leads to pleiotropic abnormalities: accelerated lymphoid
      cell death in thymus and spleen, polycystic kidney, hair hypopigmentation, and
      distorted small intestine.
AB  - Transgenic mice homozygously lacking in the bcl-2 gene were generated using
      homologous recombination in embryonal stem cells. The complete absence of Bcl-2
      alpha and -beta proteins did not interfere with normal embryonic development.
      Abnormalities became evident after birth, although the severity varied among
      homozygous null mice, bcl-2-/- mice displayed pleiotropic abnormalities similar
      to those in the previously described bcl-2-/- mice, including growth retardation,
      smaller ears, short lives, polycystic kidney, atrophic thymus and spleen with
      accelerated apoptotic cell death of lymphocytes, and hair hypopigmentation in the
      second hair follicle cycle. Our bcl-2-/- mice also revealed novel defects in the
      small intestine, characterized by retarded development, accelerated exfoliation
      of epithelial cells, and very few mitotic progenitor cells.

PMID- 7812969
TI  - Pathogenesis of ascites tumor growth: vascular permeability factor, vascular
      hyperpermeability, and ascites fluid accumulation.
AB  - Previous studies have shown that accumulation of tumor ascites fluid results in
      large part from increased permeability of peritoneal lining vessels (Nagy et al.,
      Cancer Res., 49: 5449-5458, 1989; Nagy et al., Cancer Res., 53: 2631-2643, 1993).
      However, the specific microvessels rendered hyperpermeable have not been
      identified nor has the basis of peritoneal vascular hyperpermeability been
      established. To address these questions, TA3/St and MOT carcinomas, well
      characterized transplantable murine tumors that grow in both solid and ascites
      form, were studied as model systems. Ascites tumor cells of either type were
      injected i.p. into syngeneic A/Jax and C3Heb/FeJ mice, and ascites fluid and
      plasma were collected at intervals thereafter up to 8 and 28 days, respectively.
      Beginning several days after tumor cell injection, small blood vessels located in
      tissues lining the peritoneal cavity (mesentery, peritoneal wall, and diaphragm)
      became hyperpermeable to several macromolecular tracers (125I-human serum
      albumin, FITC-dextran, colloidal carbon, and Monastral Blue B). Increased
      microvascular permeability correlated with the appearance in ascites fluid of
      vascular permeability factor (VPF), a tumor cell-secreted mediator that potently
      enhances vascular permeability to circulating macromolecules. VPF was measured in
      peritoneal fluid by both a functional bioassay and a sensitive immunofluorometric
      assay. The VPF concentration, total peritoneal VPF, ascites fluid volume, tumor
      cell number, and hyperpermeability of peritoneal lining microvessels were found
      to increase in parallel over time. The close correlation of peritoneal fluid VPF
      concentration with the development of hyperpermeable peritoneal microvessels in
      these two well-defined ascites tumors suggests that VPF secretion by tumor cells
      is responsible, in whole or in part, for initiating and maintaining the ascites
      pattern of tumor growth.

PMID- 7812970
TI  - Pathogenesis of ascites tumor growth: fibrinogen influx and fibrin accumulation
      in tissues lining the peritoneal cavity.
AB  - In the immediately preceding paper, we demonstrated that the microvasculature
      supplying peritoneal lining tissues of mice bearing either of two transplantable
      ascites carcinomas was hyperpermeable to circulating macromolecules. Solid tumors
      have been shown to exhibit similar levels of microvascular hyperpermeability,
      leading to extravasation of plasma proteins, including fibrinogen which clots on
      extravasation to form an extravascular fibrin gel. To determine whether similar
      extravasation and clotting of plasma fibrinogen occurred in ascites tumors, we
      used 125I-labeled fibrinogen (125I-F) as a tracer to measure inflow of fibrinogen
      into the peritoneal cavities, and influx and accumulation of fibrinogen/fibrin in
      the peritoneal lining tissues (peritoneal wall, mesentery, and diaphragm) of mice
      bearing syngeneic TA3/St or MOT ascites tumors. The percentage of circulating
      125I-F that extravasated into the peritoneal cavity was increased from 10- to 50
      fold in mice bearing either ascites tumor. Influx into the peritoneal walls of
      ascites tumor-bearing mice was 3-7 times that of control mice and became maximal
      on day 8 (TA3/St) and day 15 (MOT). Accumulation of 125I-F in ascites fluid and
      peritoneal lining tissues was also increased substantially in mice bearing these
      ascites tumors, reaching maximal values on days 7-8 (TA3/St) and 19-29 (MOT) at
      levels 2- to 3-fold (peritoneal wall) and 33- to 148-fold (ascites fluid) above
      control levels. Significant amounts of the 125I-F that accumulated in the
      peritoneal lining tissues of ascites tumor-bearing animals were insoluble in 3 M
      urea, consistent with clotting of 125I-F to cross-linked fibrin. Autoradiographs
      of SDS-PAGE gels performed on extracts of peritoneal lining tissues of both
      ascites tumors revealed the characteristic signature of cross-linked fibrin,
      i.e., gamma-gamma dimers and alpha-polymers. Fibrin was also identified in
      peritoneal lining tissues of both ascites tumors by immunohistochemistry. Taken
      together, these data indicate that fibrinogen, like other circulating
      macromolecules, extravasates into the peritoneal cavity and peritoneal lining
      tissues of ascites tumor-bearing mice and does so with kinetics similar to those
      of other macromolecular tracers we have studied. Moreover, a portion of the
      fibrinogen that extravasated into peritoneal lining tissues clotted to form a
      cross-linked fibrin meshwork which trapped tumor cells and favored their
      attachment to the peritoneal surface. By analogy with solid tumors, such fibrin
      deposits may also be expected to have a role in initiating angiogenesis and the
      generation of mature tumor stroma.

PMID- 7812971
TI  - Quantitative distinction of cisplatin-sensitive and -resistant mouse fibrosarcoma
      cells grown in multicell tumor spheroids.
AB  - As a suitable model to study the growth behavior and therapeutic response of drug
      resistant and -sensitive cells in three-dimensional coculture we have established
      multicellular spheroids generated from both cisplatin-sensitive and -resistant
      cells of a murine fibrosarcoma cell line. A drug resistant clone was derived from
      the parent cisplatin-sensitive cells by intermittent drug exposure in vitro. As a
      prerequisite for analysis of differential growth and treatment response of
      spheroid subpopulations, two efficient methods to discriminate between the two
      morphologically indistinguishable subpopulations in mixed spheroids were
      established. In the cisplatin-resistant cell line chosen for the present study,
      resistance is mainly due to an increased cellular metallothionein content and is
      therefore associated with increased resistance to CdCl2. Exposure of colonies to
      high concentrations of CdCl2 thus allowed selective elimination of sensitive
      colonies. Permanent labeling of either resistant or sensitive cells was achieved
      by introduction of the Escherichia coli beta-galactosidase marker gene with a
      retroviral vector system. The transformation of an uncolored galactose derivative
      by this enzyme into an indigo stain allowed detection of cells carrying and
      expressing the marker gene. The marker gene and CdCl2 method led to identical
      results when used simultaneously to distinguish quantitatively between resistant
      and sensitive colonies grown from plated cells of untreated or irradiated mixed
      spheroids. The retroviral labeling method was also used successfully in the study
      of intact spheroids, showing that in 1:1 mixed spheroids, cisplatin-sensitive
      parent cells accumulate in the spheroid periphery, outgrowing resistant cells and
      displacing them into the metabolically restricted spheroid center. Only when
      sensitive and resistant cells are initially mixed at a ratio of 1:9 are the
      resulting spheroids composed of equal proportions of the 2 cell types throughout
      10-20 days after spheroid initiation.

PMID- 7812972
TI  - Cell proliferation kinetics in human tumor xenografts measured with
      iododeoxyuridine labeling and flow cytometry: a study of heterogeneity and a
      comparison between different methods of calculation and other proliferation
      measurements.
AB  - The influence of overall treatment time in the results of fractionated radiation
      treatment was initially established in experimental tumors and, subsequently, in
      the clinic. The availability of techniques (antibodies against halogenated
      thymidine analogues and flow cytometry) which permit determinations of the
      duration of the synthesis phase, the labeling index, and the tumor potential
      doubling time (Tpot) in a short period of time and requiring only a small biopsy
      of tumor tissue, has expanded interest in the relationship between tumor cell
      proliferation and response to irradiation. A valuable tool in the study of this
      relationship are human tumor xenografts. Previous studies have shown a
      substantial intratumoral heterogeneity in the determinations of Tpot. Different
      methods of calculation of the kinetic parameters have been published. We have
      conducted a heterogeneity analysis and an evaluation of the different calculation
      methods in order to define the validity of Tpot as a proliferation rate
      measurement in human tumor xenografts. Results show the intertumoral variability
      in Tpot [between different types of human tumor xenografts systems (coefficient
      of variation = 88.2%)] to be greater than mean intratumoral variation
      (coefficient of variation = 30.8%); this suggests that this variation is
      potentially adequate to serve as a predictor of response. The diverse calculation
      methods provided significantly different absolute values but not different tumor
      ranking, probably because the time interval between labeling and sampling was
      maintained, for all the samples, between 6 and 8 h. Our study has found
      significant differences between the labeling index and the S-phase fraction
      determined with the DNA profile in 9 out of 10 tumor types. No correlation was
      found between the DNA index of the tumors in this series and their proliferation
      rate.

PMID- 7812973
TI  - Sigma-1 and sigma-2 receptors are expressed in a wide variety of human and rodent
      tumor cell lines.
AB  - Thirteen tumor-derived cell lines of human and nonhuman origin and from various
      tissues were examined for the presence and density of sigma-1 and sigma-2
      receptors. Sigma-1 receptors of a crude membrane fraction were labeled using
      [3H](+)-pentazocine, and sigma-2 receptors were labeled with [3H]1,3-di-o
      tolylguanidine ([3H]DTG); in the presence or absence of dextrallorphan. [3H](+)
      Pentazocine-binding sites were heterogeneous. In rodent cell lines (e.g., C6
      glioma, N1E-115 neuroblastoma, and NG108-15 neuroblastoma x glioma hybrid), human
      T47D breast ductal carcinoma, human NCI-H727 lung carcinoid, and human A375
      melanoma, [3H](+)-pentazocine bound to high- and low-affinity sites with Kd1 =
      0.67-7.0 nM, Bmax1 = 25.5-108 fmol/mg protein, Kd2 = 127-600 nM, and Bmax2 = 942
      5431 fmol/mg protein. However, [3H](+)-pentazocine bound to a single site in
      other cell lines. In human U-138MG glioblastoma, SK-N-SH neuroblastoma, and
      LNCaP.FGC prostate, Kd = 28-61 nM and Bmax = 975-1196 fmol/mg protein, whereas in
      ThP-1 leukemia Kd = 146 nM and Bmax = 1411 fmol/mg protein. The sigma-1-like
      nature of [3H](+)-pentazocine-binding sites was confirmed by competition studies
      which revealed high affinity for haloperidol and enantioselectivity for (+)
      pentazocine over (-)-pentazocine. Interestingly, human MCF-7 breast
      adenocarcinoma showed little or no specific binding of [3H](+)-pentazocine,
      suggesting the absence of sigma-1 receptors in this cell line. All cell lines
      examined expressed a high density of sigma-2 receptors with Kd values for [3H]DTG
      ranging from 20 to 101 nM and Bmax values of 491 to 7324 fmol/mg protein.
      Competition studies indicated possible heterogeneity of sigma-2 receptors. While
      sites labeled by [3H]DTG in all cell lines tested exhibited affinity for
      haloperidol and preference for (-)-pentazocine over the (+)-enantiomer, human
      cell lines generally showed 4- to 7-fold lower affinity for haloperidol and
      approximately 10-fold lower affinity for (-)-pentazocine compared with the rodent
      cell lines. The high density of sigma-1 and sigma 2-binding sites in these cell
      lines suggests important cellular functions in cancer, as well as potential
      diagnostic utility for tumor-imaging agents which target sigma sites. These cell
      lines may be useful as model systems in which to study the functions of sigma
      sites in normal tissues, as well as their possible role in tumor biology.

PMID- 7812974
TI  - Cell type-specific fingerprinting of meningioma and meningeal cells by proton
      nuclear magnetic resonance spectroscopy.
AB  - We compared the properties of six human meningiomas with normal rat meningeal
      cells using cell culture techniques, high resolution in vitro 1H-NMR (nuclear
      magnetic resonance) spectroscopy, and chromatographic analysis. Cell cultures
      were immunocytochemically characterized at all stages with specific antibodies.
      Quantitative and qualitative metabolite assessments in cell extracts were
      obtained from 1H-NMR spectra and chromatographic analysis. Human meningioma cells
      expressed a characteristic spectrum of metabolites including free amino acids,
      compounds related to membrane phospholipid metabolism, energy metabolites, and
      other intermediary products. These spectral characteristics, although different
      in some respects, were strikingly similar to the ones of rat meningeal cells.
      Particularly, several metabolites that allow discrimination between meningeal
      cells and other cell types of the central nervous system were preserved in
      meningiomas. These similarities suggest that the regulation of intracellular
      levels of such metabolites is so intrinsic to the identity of cell type as to be
      conserved across species and through transformation. Additionally, human
      meningioma cultures expressed some spectroscopic characteristics that enabled
      them to be clearly distinguished from primary rat meningeal cultures. Thus, human
      meningiomas may be both specifically recognizable by 1H-NMR spectroscopy and also
      distinguishable from normal rat meningeal tissue. Our results raise the eventual
      possibility of using NMR in the noninvasive diagnosis of brain tumors in vivo.

PMID- 7812976
TI  - 2-Deoxy-D-glucose enhances sensitivity of human histiocytic lymphoma U937 cells
      to apoptosis induced by tumor necrosis factor.
AB  - It has been reported that the cytotoxic effect of tumor necrosis factor (TNF) on
      cells of several tumor cell lines was potentiated in culture media lacking
      glucose. Also, the antitumor effect of TNF was shown to be enhanced in vivo in
      mice treated with insulin to reduce their blood glucose level. The present study
      was aimed to reveal whether (a) the administration of the glucose antimetabolite
      2-deoxy-D-glucose (2DG) has an effect similar to that of reduction of the
      extracellular glucose concentration; (b) the combined treatment with TNF and 2DG,
      similar to TNF alone, leads to apoptosis; and (c) there is a preference of cells
      in a particular phase of the cell cycle to undergo apoptosis in the presence of
      these agents. Exponentially growing human histiocytic lymphoma U937 cells were
      exposed to 0.1-0.5 nM of recombinant human TNF-alpha in the absence and presence
      of 1.0-5.0 mM 2DG. Analysis of the cell proliferation rates and their viability
      revealed that cytotoxicity of TNF was markedly potentiated by 2DG. Thus,
      administration of 1.0 mM 2DG to the cultures treated with 0.3 nM recombinant
      human TNF-alpha increased by 2-3-fold the percentage of dead cells after 24-72 h.
      The antimetabolite alone, at that low concentration, showed minimal cytotoxicity.
      More than additive cytotoxic effects also were seen at 2.5 and 5.0 mM
      concentrations of 2DG. Apoptosis was identified by typical changes in cell
      morphology, preferential degradation of internucleosomal DNA, and in situ
      extensive DNA strand breakage. The number of cells with DNA strand breaks after
      24-h incubation was increased from 13% (0.1 nM TNF alone) to 20 or 45% in the
      presence of 2.5 or 5.0 mM 2DG, respectively. There was no evidence of a
      significant cell cycle phase preference in induction of apoptosis by combined
      treatment with recombinant human TNF-alpha and 2DG, although 2DG alone reduced
      the percentage of cells in S and G2 + M, apparently by arresting cells in G1.
      These data, along with observations in other cell systems, suggest that
      simultaneous stimulatory signals for growth induction, presumed to be provided by
      TNF, and growth suppression (inhibition of glycolysis) may preferentially trigger
      apoptosis of transformed cells. The data also suggest that 2DG may be an
      effective adjunct to TNF in the clinic, increasing the antitumor potency of this
      cytokine.

PMID- 7812975
TI  - The human tumor cell-derived collagenase stimulatory factor (renamed EMMPRIN) is
      a member of the immunoglobulin superfamily.
AB  - Tumor cell-derived collagenase stimulatory factor, renamed extracellular matrix
      metalloproteinase inducer (EMMPRIN), is a M(r) approximately 58,000 glycoprotein
      which is located on the outer surface of human tumor cells and which interacts
      with fibroblasts to stimulate expression of several matrix metalloproteinases in
      the fibroblasts. In this study, we have used several approaches to isolate a
      complementary DNA encoding EMMPRIN. Several peptide sequences obtained from the
      isolated M(r) 58,000 glycoprotein are found in the translated complementary DNA
      clone, verifying its identity. Computer database searches indicate that EMMPRIN
      is a member of the immunoglobulin superfamily and that the deduced amino acid
      sequence of EMMPRIN is identical to that recently reported for human basigin and
      M6 antigen, molecules of previously undetermined biological function.

PMID- 7812977
TI  - Keystone symposium on complex carbohydrates in biology and medicine: cancer.

PMID- 7812978
TI  - Human T-lymphotropic virus type-I influence on hepatotropic virus infections and
      the subsequent development of hepatocellular carcinoma.
AB  - We studied the serologic status, with respect to hepatitis B virus (HBV),
      hepatitis C virus (HCV), and human T-lymphotropic virus type-I (HTLV-I) of blood
      donors in an area endemic for adult T-cell leukemia (ATL). Similarly, we studied
      the serologic status of hepatocellular carcinoma (HCC) patients from the same
      district. In the donors, the incidence of serological positivity for these
      viruses was 0.95, 1.23, and 3.75%, respectively. There was a positive correlation
      between the presence of anti-HCV and serological HTLV-I positive status in these
      subjects (1.9 vs. 1.1%) for those with HTLV-I negative status, implying high
      susceptibility for HCV infection among HTLV-I carriers. Fifty-nine percent of HCC
      patients were positive for anti-HCV and twenty-six percent of those were
      simultaneously positive for the antibody to HTLV-I. HCC patients infected with
      HTLV-I were younger than patients not so infected (61.5 +/- 8.8 vs. 64.8 +/- 8.4
      years, p < 0.05). These observations suggest the possibility that HTLV-I could be
      one of the factors that promote the development of HCC caused by hepatotropic
      viruses.

PMID- 7812979
TI  - Multistep alterations of human lymphocytes infected with HTLV-I and then exposed
      to carcinogens.
AB  - Normal human lymphocytes achieved continuous growth in IL-2-containing medium in
      vitro following HTLV-I infection. They showed specific structural abnormalities
      of certain chromosomes. Subsequent to exposure to MNNG and TPA, or to UV, they
      achieved autonomous growth (transformation). Alterations in the signal
      transduction system were observed in transformed cells that showed loss of
      ability to grow in the medium containing TPA. Additional chromosome abnormalities
      appeared in transformed cells. These abnormalities were found to cluster to
      chromosomes that had preexisting structural abnormalities. Changes of the met
      gene on chromosome 7, to which structural abnormalities were observed clustering,
      were detected by Southern blot analysis. Environmental carcinogens may work as
      cofactors to promote transformation of human lymphocytes infected with HTLV-I.
      The initial change of human lymphocytes caused by HTLV-I integration may be
      advanced toward neoplastic transformation by their exposure to other carcinogens.

PMID- 7812980
TI  - Correlation between family history of colorectal cancer and pathological and
      clinical features of the disease.
AB  - Familial aggregation of colorectal cancer occurs even among sporadic cases that
      are not part of defined genetic syndromes. First-degree relatives of patients
      with "sporadic" colorectal cancer have a three- to fourfold increased risk of the
      same cancer. The aim of the present study is to investigate the relationship
      between a first-degree family history of colorectal cancer and the pathological
      and clinical features of the tumor (site, Dukes' stage, age at diagnosis, sex,
      and patient survival). Four hundred and sixty-one patients with colorectal cancer
      were evaluated (250 males and 211 females) and information obtained on their
      family history of cancer. Sex, age, and stage of disease were the only parameters
      that correlated significantly with survival. No relationship between family
      history of colorectal cancer and the prognostic variables was observed.

PMID- 7812981
TI  - Lung cancer in the young.
AB  - Lung cancer is uncommon in individuals age 40 or less. We reviewed the Cancer
      Registry files of the Ben Taub General Hospital (Houston, TX) from 1971 to 1989
      and identified 1678 patients with a documented diagnosis of lung cancer. Among
      these 1678 patients, 50 (2.98%) were age 40 or less. Thirty-five (70%) of the 50
      patients were men and 15 (30%) were women. Their median age was 37 (range of 24
      to 40). A smoking history was available in 37 patients. Thirty-five (94.5%) of
      the 37 patients who were smokers had a > 20-pack per year history of smoking.
      Four patients were intravenous drug abusers, and one of these four tested
      positive for the immunodeficiency virus. Twenty-seven (54%) had adenocarcinoma,
      eight (16%) had squamous cell carcinoma, and six (12%) had other nondescript,
      nonsmall-cell carcinoma types. In contrast, the proportion of adenocarcinoma for
      the (all-age) group of 1678 patients with lung cancer was 28.2%. This difference
      in the proportion of adenocarcinoma between the two age groups was statistically
      significant (Pearson's Chi 2, 13.7039, p < 0.0005). Thirty-one (77.5%) of the 50
      patients had unresectable disease at diagnosis (12 had stage IIIb and 19 had
      stage IV). The median survival from diagnosis was 26 weeks. These findings
      suggest that (1) smoking is an important risk factor for this subset of young
      patients, (2) the proportion of adenocarcinoma is higher in the young compared
      with the entire group of lung cancer patients, which included patients of all
      ages, and (3) young patients tend to present with advanced disease at diagnosis,
      resulting in an extremely poor survival.

PMID- 7812982
TI  - Increased levels of a 21-kDa protein in the circulation of tumor-bearing
      patients.
AB  - A novel non-ras 21-kDa protein (p21) was detected in sera of cancer patients by
      enzyme-linked immunosorbent assay (ELISA), using polyclonal anti-p21 antibodies.
      While only 4.6% of the healthy donors (n = 43) showed p21 serum levels higher
      than the mean +/- 2 SD of the normal group, 33 to 80% of the cancer patients (n =
      94) with various tumors were positive in the ELISA test. In particular, patients
      with malignant lymphoma, urogenital, and gastrointestinal tumors had a 2.8- to
      ninefold increase in p21 serum levels. Elevated serum levels were also found in
      patients with benign prostatic hyperplasia (3.2-fold increase). In 17 out of 22
      patients with urogenital tumors, changes in serum p21 levels correlated with the
      clinical course of the disease. In 15 patients, a favorable response to therapy
      was correlated with a decline in serum p21 level. Two patients with renal cell
      carcinoma showed increased or persistently high levels of p21 after surgery and
      were subsequently found to have distant metastases. Expression of p21 in ten
      renal cell carcinoma tissues was determined by Western blotting. There was a
      trend toward a higher content of p21 in the less-differentiated tumor tissues. In
      conclusion, p21 may be a useful indicator in monitoring the outcome of treatment
      in patients with various malignant tumors. In patients with renal cell carcinoma,
      p21 serum levels may be of particular importance because no other tumor marker is
      available.

PMID- 7812983
TI  - The expression of HLA-DR antigen in cervical neoplasia.
AB  - The purpose of this study was to evaluate the relationship between cervical
      neoplasia and HLA-DR antigen (class II antigen) expression. Seventy-seven
      formaldehyde-fixed uterine specimens comprising morphologically normal cervix
      (12), chronic cervicitis (10), cervical intraepithelial neoplasia (CIN) of
      various grades (42), and invasive squamous cell carcinoma (13) were studied for
      the degree and type of inflammation, and immunohistochemically for the HLA-DR
      antigen expression in the epithelium. The nonneoplastic ectocervical squamous
      epithelium was consistently negative for HLA-DR antigen, even in sections showing
      significant lymphoplasmacytic infiltration. We found HLA-DR antigen positivity in
      endocervical glandular epithelium, immature metaplastic squamous epithelium, CIN,
      and invasive carcinoma. In cases of CIN, the aberrant expression of the antigen
      generally corresponded to the level of dysplasia. Specific cells exhibiting
      koilocytic change were negative. All the cases of squamous cell carcinoma
      expressed the antigen, albeit variable in intensity and distribution. These
      findings suggest that aberrant HLA-DR antigen expression in the uterine
      ectocervix may be a consequence of dysplastic changes of the squamous epithelium
      that is maintained even after malignant transformation. On the other hand, HLA-DR
      positivity in immature metaplastic epithelium is probably a mere reflection of
      the fact that normal endocervical glandular epithelium can express the antigen.

PMID- 7812984
TI  - Breast imaging: a comparison of digital luminescence radiographs displayed on TV
      monitor and film-screen mammography.
AB  - The purpose of this study was to compare the diagnostic accuracy of conventional
      film-screen mammograms with the corresponding digital luminescence mammograms
      saved on optical disk and viewed on a 1240-line monitor. One hundred mammograms
      from 100 patients, including 17 biopsy-proven cancers and one cancer confirmed by
      cytology, were reviewed. Five radiologists with different mammography experience
      served as observers, and receiver operating characteristic (ROC) curves were
      constructed. The result of the monitor interpretation was not inferior to the
      conventional mammogram interpretation. One observer with vast mammography
      experience obtained excellent results with a digital interpretation.

PMID- 7812985
TI  - Cell type identification in leukemia: the level of agreement among four
      independent diagnostic methods.
AB  - The level of agreement among four independent diagnostic methods for cell-type
      identification in leukemia was examined. The four diagnostic methods were routine
      morphology, electron microscopy, cell surface marker analysis by flow cytometry,
      and cancer cytogenetics. Sixty-five blood and bone marrow samples from fifty
      seven patients were independently investigated by the four methods. It was found
      that when all cell-type categories were taken into consideration, overall
      percentages of agreement for pairs of the four diagnostic methods were poor,
      ranging from 43% to 67%. The kappa statistics, which correct for the agreement
      expected by chance, were also calculated. These kappa statistics had a range from
      0.17 to 0.40 when all cell-type categories were taken into consideration, again
      indicating poor agreement between the methods pairwise. When each cell type was
      considered separately, much of the observed agreement was found to be expected on
      the basis of chance, as indicated by many of the kappa statistics being 0.00. For
      all categories, overall agreement for all four methods was poor and statistically
      significant, after correcting for chance (kappa = 0.20, (p = 0.000046). The poor
      agreement found among the four diagnostic methods indicates the need for further
      validation studies.

PMID- 7812986
TI  - Tumor cell kinetics following long-term treatment with antineoplastic ether
      phospholipids.
AB  - Ether phospholipids are analogs of the naturally occurring 2
      lysophosphatidylcholine that have been reported to have selective in vitro/in
      vivo antitumor activity. Their antiproliferative effect has been found against a
      variety of animal and human tumor cell lines. We have characterized the
      cytostatic activity of four ether phospholipids, the methoxy-substituted
      edelfosine (ET-18-OCH 3), the thio-derivative ilmofosine (BM 41.440), and two new
      aza-alkylphospholipids, BN 52205 and BN 52211, on a human tumor cell line derived
      from a colon adenocarcinoma, the HT29. A flow cytometric approach has been used
      and, contrary to previous studies, longer treatment times have been performed to
      allow multiple cell population doublings. The results confirm that the cytostatic
      activity of the four ether phospholipids is characterized by multiple "terminal
      points", as the drugs' action results in a G1 block, a slowdown of the transition
      from late-S to G2, followed by an accumulation of HT29 cells in the G2 phase of
      the cell cycle. Tumor cells in late G1 at the time of treatment progressed
      through S before being blocked in G2. In a similar fashion, tumor cells in late
      G2 at the time of treatment went through M but were then halted in G1. The long
      term treatment studies indicate that the ether phospholipid cytostatic activity
      is partially reversible, depending on the drug concentration and the duration of
      the treatment.

PMID- 7812987
TI  - Dietary cottonseed protein can reduce the severity of retinoid-induced
      hypertriglyceridemia.
AB  - Hypertriglyceridemia is frequently noted as a side effect when retinoids (e.g.,
      13-cis-retinoic acid) are used in human chemoprevention trials. Dietary oilseed
      proteins (e.g., cottonseed and soy protein) are known to reduce the severity of
      diet-induced hypertriglyceridemia, but their influence on drug-induced
      hypertriglyceridemia has not been studied previously. In the present study, the
      ability of dietary cottonseed protein (as cottonseed flour) to prevent drug
      induced hypertriglyceridemia was investigated by feeding male Fischer 344 rats
      diets having casein or cottonseed protein flour with or without 13-cis-retinoic
      acid. Animals were fed diets for 2 weeks. Retinoid administration was associated
      with the induction of hypertriglyceridemia and with changes in serum fatty acid
      profile, the most noticeable being lowered levels of arachidonic acid. Levels of
      this fatty acid were 35 and 54% of control levels for retinoid-treated animals
      fed casein and cottonseed flour, respectively. Animals fed cottonseed flour had
      lower serum triglyceride levels than ones fed casein for both retinoid-containing
      and control diets. Dietary cottonseed flour had no effect on food intake or body
      weight and did not affect serum drug levels. Thus, dietary cottonseed protein can
      reduce the severity of retinoid-induced hypertriglyceridemia without having
      adverse effects on food intake or growth; in addition, because levels of 13-cis
      retinoic are unaffected by cottonseed protein, it is unlikely that the
      chemopreventive effectiveness of the drug will be compromised by the inclusion of
      this protein in the diet.

PMID- 7812988
TI  - Multidrug resistance gene and P-glycoprotein expression in anaplastic carcinoma
      of the thyroid.
AB  - The resistance of malignant tumors to chemotherapy with anticancer drugs has been
      considered to be due partly to overexpression of the multidrug resistance gene
      (mdr1) and its gene product, P-glycoprotein (P-GP), which acts as a drug efflux
      pump for several chemotherapeutic agents. In order to elucidate the mechanism of
      anticancer drug resistance in anaplastic thyroid carcinoma with very poor
      prognosis, we examined the expression of mdr1 mRNA and P-GP, and analyzed their
      relationships to chemotherapy response. Twenty surgical samples from 16 patients
      with anaplastic thyroid carcinoma were used. The mdr1 mRNA expression was
      examined by reverse transcription and polymerase chain reaction, and P-GP
      expression was evaluated by an immunohistochemical method using JSB-1 monoclonal
      antibody. Of the 20 clinical samples, expression of mdr1 mRNA and P-GP was
      observed in three and four samples, respectively. Three of the patients from whom
      the samples were obtained had been given anticancer drugs before biopsy. Of 12
      patients who received chemotherapy for clinically evaluable diseases, 2 responded
      well, but 10 showed no response. All except one patient died of cancer
      progression. There was no relationship between the response to chemotherapy and
      the expression of mdr1 and P-GP. The expression of mdr1 mRNA and/or P-GP was
      observed in 5 of 16 patients with anaplastic thyroid carcinoma. However, the
      appearance of anticancer drug resistance in anaplastic thyroid carcinoma may not
      be explained solely by the expression of mdr1 and P-GP.

PMID- 7812989
TI  - Reduced semen quality and risk behaviour amongst men consulting a referral STD
      clinic.
AB  - Sexually transmitted diseases (STDs) and infertility are public health challenges
      that continue to represent a high demand and costly adult medical care conditions
      in most developing countries. Few studies address strategies for prevention of
      infertility secondary to STDs through behavioural change and early and prompt STD
      treatment. A prospective cohort design was used to study the effects of
      urogenital infection on semen quality in consenting consecutive subjects that
      presented with chronic or recurrent sexually transmitted diseases. Health seeking
      behavioural correlates and socio-economic variables were compared between index
      subjects at a genito-urinary referral clinic and those that presented with non
      STD conditions at a referral polyclinic.

PMID- 7812990
TI  - Lymphoproliferative malignancies in association with endemic African Kaposi's
      sarcoma.
AB  - The association of classical Kaposi's sarcoma with lymphoproliferative disorders
      is well known. However, far less is known about lymphoproliferative malignancies
      in endemic African Kaposi's sarcoma. A review of 47 patients with the endemic
      type of Kapos's sarcoma treated at the Johannesburg Teaching Hospital Complex
      between 1980 and 1992 revealed four patients (8.5 pc) in whom Kaposi's sarcoma
      was associated with a malignant lymphoma. Possible pathogenetic mechanisms are
      suggested and the current literature is reviewed.

PMID- 7812991
TI  - Determination of appropriate clomipramine dosage among depressed African
      outpatients in Dar es Salaam, Tanzania.
AB  - In an open clomipramine dose finding study, 33 depressed indigenous African
      outpatients were randomly assigned to two regimens of treatment with 125 mg and
      75 mg oral medications daily. At the end of eight weeks of treatment, 16 patients
      (48.5 pc) were on the 75 mg regime, and 17 (54.8 pc) were on 125 mg. Analysis of
      depression scores on the Beck-Rafaelsen scale indicated improvements of
      depression in both regimes of equal magnitude. Analysis of variance showed no
      statistically significant difference on dose response between the two regimes.
      The higher doses, however, were associated with more drowsiness and
      tremulousness. It is suggested that Black African patients respond to tricyclic
      antidepressants in much lower doses than those recommended in Western textbooks.
      It is also apparent that side effects of tricyclic antidepressants, which have
      been implicated in non-compliance to medication, could be avoided without
      compromising treatment outcome.

PMID- 7812992
TI  - Bronchoscopic extraction of aspirated foreign bodies in children in Harare
      Central Hospital, Harare, Zimbabwe.
AB  - Fifty eight children underwent rigid bronchoscopy under general anaesthesia for
      suspected aspirated foreign bodies. There were 36 boys and 22 girls with a mean
      age of 18 months. Physical examination showed decreased breath sounds and
      wheezing over the affected site in 47 cases. CXR's were diagnostic in 11 cases
      showing a definite radio opaque shadow suggestive of aspirated foreign body in 35
      (60 pc). Three patients had negative results at bronchoscopy (5.4 pc). Extraction
      of foreign bodies was performed by forceps under direct vision at bronchoscopy in
      55 patients. Two children had an intra-operative hypoxic arrest. Post endoscopic
      complications included mild to moderate croup in 15 patients, fever in four and
      pneumothorax in one. Rigid bronchoscopy of aspirated foreign bodies in children
      is a safe, effective and often life saving procedure. Morbidity is low and
      although mortality was 1.8 pc in this series zero mortality should be achievable.

PMID- 7812993
TI  - Importance of intersectoral co-ordination in the control of communicable
      diseases, with special reference to plague in Tanzania.
AB  - Human health, agriculture, including livestock, energy, education, wildlife,
      construction, forestry and trade sectors are inter-related and their co
      ordination is an important pre-requisite for successful control of most
      communicable diseases including plague. Similar linkage between research, policy,
      training and extension activities in each sector are essential for any successful
      control strategy. Inadequate agricultural produce, inaccessibility of people to
      the available food and ignorance on proper preparation and usage of available
      food materials are responsible for malnutrition, and malnourished people are very
      vulnerable to disease. Irrigation schemes facilitate breeding of various disease
      vectors and transmission of some communicable diseases. Forests are ecologically
      favourable for some disease vectors and reservoirs for tsetse flies and rodents,
      while deforestation leads to soil erosion, lack of rainfall and consequently
      reduced productivity in agriculture which may result in poor nutrition of the
      population. Wildlife and livestock serve as reservoirs and/or carriers of various
      zoonoses including plague, trypanosomiasis and rabies. Lack of proper co
      ordination of these sectors in communicable disease control programmes can result
      in serious and undesirable consequences. Indiscriminate killing of rodents in
      order to minimize food damage by these vermin forces their flea ectoparasites to
      seek alternative hosts, including man, a development which may result in
      transmission of plague from rodents to man. Similarly, avoidance of proper
      quarantine during plague epidemics, an undertaking which is usually aimed at
      maintaining economic and social links with places outside the affected focus, can
      result in the disease becoming widespread and consequently make any control
      strategies more difficult and expensive.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7812994
TI  - Prolapsed pedunculated sub-mucous uterine fibroleiomyomata at the University
      Teaching Hospital, Lusaka.
AB  - During a two year period 901 cases were admitted and diagnosed as benign
      gynaecological neoplasms. Five hundred and thirty three of these (59.1 pc) were
      uterine fibroleiomyomata. Of these, 103 had surgery and 13 (12.6 pc) had
      pedunculated fibroleiomyomata presenting as a vaginal mass. Eight of the 13 cases
      were treated by vaginal myomectomy. Total abdominal hysterectomy was carried out
      in two cases because of failed vaginal myomectomy. Two others had total abdominal
      hysterectomy for dysfunctional uterine bleeding and for satisfied parity. One
      case absconded. Vaginal myomectomy should be the first choice of treatment for
      prolapsed submucous leiomyomata. However, in cases with concurrent gynaecological
      problems or those cases with satisfied parity, total abdominal hysterectomy
      should be considered. Specific antibiotics should be used pre and post
      operatively in cases with necrotic tumours.

PMID- 7812995
TI  - Advances in electrodiagnosis in Zimbabwe. Part I: Peripheral nerve conduction
      studies and electromyography.
AB  - This paper reviews the two electrodiagnostic techniques--nerve conduction
      measurements and electromyography. A brief description of each technique is given
      followed by their clinical applications. Finally the types of abnormalities
      observed are discussed and where possible, illustrated.

PMID- 7812996
TI  - Neoplasms involving the spinal cord in Zimbabweans: an analysis of 262 cases.
AB  - A review of 262 histologically verified spinal cord tumours in Black Zimbabweans
      who were operated on in Harare Central and Parirenyatwa Hospitals, Harare,
      Zimbabwe during the period 1st January 1972 to 31st December 1991 is presented.
      Fifty one pc of the neoplasms were found in the thoracic region, 53.4 pc were
      found extradurally, and of these the majority were metastatic (52 pc) and
      malignant tumours (85 pc). Most (96 pc) intradural-extramedullary tumours were
      benign with Schwannomas as the largest group (54 pc). Malignant astrocytomas
      presented as 71.4 pc of all intramedullary tumours. Metastatic tumours
      represented 28.6 pc of all spinal cord tumours. The most common sites of
      metastasis were from liver, thyroid and prostate.

PMID- 7812997
TI  - Termination of pregnancy using extra-amniotic prostaglandin F2a--experience in a
      peripheral hospital.
AB  - Extra-amniotic injection of prostaglandin F2a has proved to be an effective
      method of termination of pregnancy, although its use has been associated with
      serious complications including rupture of the uterus and maternal death. In this
      retrospective study of 45 patients who required termination of pregnancy in
      Eshowe Hospital for intra-uterine death or missed abortion two patients developed
      minor complications of this method. Forty four patients aborted between four
      hours 30 minutes and 18 hours 15 minutes after the injection. There was one
      patient who had a failed induction and who developed serious sepsis. It is not
      clear whether the sepsis was a result of the method used to induce labour or
      whether it was the primary pathology causing the intra-uterine death and failed
      induction.

PMID- 7812998
TI  - Epidemiological study of drug use in urban and rural secondary schools in
      Zimbabwe.
AB  - In this survey a total of 2,783 secondary school students of both sexes, mean age
      15.5 years, from randomly selected schools in both rural and urban areas of
      Zimbabwe were studied using a self report questionnaire. The results strongly
      indicated that drug use was quite prevalent among the students. The main drugs
      involved, in descending order, were: alcohol, tobacco, inhalants (solvents),
      amphetamines and cannabis. Others included mandrax, tranquilisers, sedatives and
      the hallucinogen mudzepete. No students reported use of heroin, cocaine, LSD or
      opium. Drug use increased with age and involved both sexes, the problem being
      more acute in the urban schools. A differential use pattern is revealed, implying
      valuable information for targeted prevention efforts.

PMID- 7812999
TI  - A comparison of three types of "M" traps for sampling tsetse fly (Diptera:
      Glossinidae) populations at south Luangwa game management area, Zambia.
AB  - A field trial was conducted between 27th July and 1st August, 1992 in Mfuwe,
      south Luangwa, Zambia to assess the effectiveness of locally developed "M" traps
      for suppressing and sampling the tsetse flies Glossina pallidipes Austen and
      Glossina morsitans morsitans Westwood. The tsetse catches in the "M" traps and
      the standard F3 traps were collected at 24 hour intervals. The highest catches of
      both tsetse species in the series of "M" traps were in the M3 trap. The numbers
      of female flies caught for both species in all the trap types were significantly
      higher than those for male flies (p < 0.001). Trap catches for G. pallidipes were
      uniformly distributed among the M2, M3 and F3 traps. In contrast, there was a
      significant drop in the M1 catches. For G. m. morsitans, the results were not
      significantly different between the M1 and the M3 catches. Based on the results
      of this trial, it is been recommended adopting the M1 trap, a more cost effective
      trap for suppression and the M3 trap for sampling of G. m. morsitans which is the
      only species in Kampumbu (our trial suppression area) in the Isoka district of
      Zambia.

PMID- 7813000
TI  - Increased susceptibility of erythrocyte membrane lipids to peroxidation in sickle
      cell disease.
AB  - Erythrocytes from normal subjects and from cases of sickle cell disease were
      exposed to hydrogen peroxide and the extent of membrane lipid peroxidation
      studied. Significantly increased peroxidation was observed in intact
      erythrocytes, isolated lipids from intact erythrocytes or their ghosts compared
      with normal controls. However, the extent of lipid peroxidation was less for
      isolated lipids of intact erythrocytes or their ghosts. This difference may be
      due to loss of factors enhancing peroxidation in intact erythrocytes in the
      extraction procedure. It is likely that damage to erythrocyte membranes caused by
      increased susceptibility to lipid peroxidation may be a factor in some of the
      haematological features of sickle cell disease.

PMID- 7813001
TI  - Intracranial Burkitt's lymphoma with extension into orbital spaces resulting in
      bilateral blindness.

PMID- 7813002
TI  - Munchausen syndrome by proxy--a case report and review of literature.
AB  - A case of a two and half year old "poor male child" who was subjected to
      potentially dangerous investigations and therapy due to factitious illness
      presented by the mother is reported. It took about two years before the problem
      could be diagnosed. Even though the mother denied the factitious nature of the
      illness, confronting her with the problem has led to a considerable reduction in
      medical consultations. The patient was still being followed up at the time of
      writing this report.

PMID- 7813003
TI  - Hypothyroxinemia in acquired immune deficiency syndrome (AIDS).
AB  - Serum thyroxine (T4) and thyroid stimulating hormone (TSH) were studied in 38
      patients confirmed to be infected with HIV-1 virus and the results compared with
      values observed in age matched healthy subjects. The mean serum total T4 in the
      majority of the patients, 103 +/- 32 nmol/L, was similar to values observed in
      the controls, 102 +/- 21 nmol/L, p > 0.05. However, 22.2 pc of the HIV-1 infected
      patients had total serum T4 values that were significantly lower than values in
      the controls, 36 +/- 12 nmol/L, p < 0.001. Since hypothyroxinemia has been
      associated with increased mortality in critical illness, we suggest that
      assessment of thyroid function may be helpful in the management of some patients
      with AIDS.

PMID- 7813004
TI  - Advances in electrodiagnosis in Zimbabwe. Part II: "Evoked potentials".
AB  - This paper is a short review of the electrodiagnostic technique of "evoked
      potentials", a technique recently introduced to Zimbabwe. The types of evoked
      potentials recorded, the method of recording and their clinical applications are
      discussed. Abnormal evoked potentials from a variety of neurological disorders
      are illustrated. "Advances in electrodiagnosis in Zimbabwe" Part I discussed
      peripheral nerve conduction measurements and electromyography. This paper (Part
      II) will review the physiological basis of "Evoked Potentials" and their clinical
      applications.

PMID- 7813005
TI  - Genes for SMA: multum in parvo.

PMID- 7813006
TI  - Can Hsp70 proteins act as force-generating motors?

PMID- 7813007
TI  - Hypermutation generating the sheep immunoglobulin repertoire is an antigen
      independent process.
AB  - Somatic hypermutation of light chain V genes during development of B cells in
      sheep ileal Peyer's patches was studied in three experimental conditions: in
      sterile fragments of the ileum surgically isolated from the gut during fetal
      life, in germ-free sheep, and in animals thymectomized during early fetal life.
      The somatic mutation pattern was found identical to control tissues in all three
      experiments. The same age-dependent amount of mutations, a higher than
      theoretical R/S ratio in complementarity-determining regions (CDRs), and a
      similar clustering of mutations in CDRs were observed. The mechanism, as
      estimated from the silent mutation pattern, appears to target mutations to CDRs;
      moreover, the major V lambda genes have a specific codon usage with a high purine
      content at the first two bases of the codons and a low content at the third
      position, which, together with a specific targeting of mutations to purines,
      favors replacement mutations in CDRs.

PMID- 7813008
TI  - Mitochondrial protein import: reversible binding of the presequence at the trans
      side of the outer membrane drives partial translocation and unfolding.
AB  - The mechanism of translocation of matrix-targeted, cleavable preproteins across
      the mitochondrial outer membrane was studied using purified outer membrane
      vesicles. The N-terminal presequence interacts in a sequential and reversible
      fashion with two specific binding sites. The first one is provided by protease
      sensitive receptors on the surface of the membrane (cis site); the second one is
      located at the inner face of the outer membrane (trans site). Binding to the
      trans site drives translocation of the N-terminal portion of the preprotein and,
      at the same time, unfolding of its mature part. We suggest that the outer
      membrane protein import machinery forms a translocation channel that permits
      reversible sliding of preproteins and prevents their lateral aggregation in the
      membrane. Although translocation can be initiated by the outer membrane, its
      completion requires coupling to the energetic system of the inner membrane. Our
      data assign an essential role to the presequence, not only for efficient
      targeting, but also for the translocation step.

PMID- 7813009
TI  - Glycogen synthase kinase 3 regulates cell fate in Dictyostelium.
AB  - Extracellular cyclic AMP (cAMP) induces the formation of prespore cells in
      Dictyostelium but inhibits stalk cell formation. We have cloned gskA, which
      encodes the Dictyostelium homolog of glycogen synthase kinase 3 (GSK-3), and
      discovered that it is required for both cAMP effects. Disruption of gskA creates
      a mutant that aggregates but forms few spores and an abnormally high number of
      stalk cells. These stalk cells probably arise from an expanded prestalk B (pstB)
      cell population, which normally produces the basal disc of the fruiting body. In
      cultured mutant cells, cAMP neither inhibits pstB cell differentiation nor
      induces efficient prespore cell differentiation. We propose that cAMP acts
      through a common pathway that requires GSK-3 and determines the proportion of
      prespore and pstB cells.

PMID- 7813010
TI  - Strong voltage-dependent inward rectification of inward rectifier K+ channels is
      caused by intracellular spermine.
AB  - Inward rectifier K+ channels mediate the K+ conductance at resting potential in
      many types of cell. Since these K+ channels do not pass outward currents (inward
      rectification) when the cell membrane is depolarized beyond a trigger threshold,
      they play an important role in controlling excitability. Both a highly voltage
      dependent block by intracellular Mg2+ and an endogenous gating process are
      presently assumed to underly inward rectification. It is shown that strong
      voltage dependence of rectification found under physiological conditions is
      predominantly due to the effect of intracellular spermine. Physiological
      concentrations of free spermine mediate strong rectification of IRK1 inward
      rectifier K+ channels even in the absence of free Mg2+ and in IRK1 mutant
      channels that have no endogenous rectification.

PMID- 7813011
TI  - The adipocyte: storage depot or node on the energy information superhighway?

PMID- 7813012
TI  - Identification and characterization of a spinal muscular atrophy-determining
      gene.
AB  - Spinal muscular atrophy (SMA) is a common fatal autosomal recessive disorder
      characterized by degeneration of lower motor neurons, leading to progressive
      paralysis with muscular atrophy. The gene for SMA has been mapped to chromosome
      5q13, where large-scale deletions have been reported. We describe here the
      inverted duplication of a 500 kb element in normal chromosomes and narrow the
      critical region to 140 kb within the telomeric region. This interval contains a
      20 kb gene encoding a novel protein of 294 amino acids. An highly homologous gene
      is present in the centromeric element of 95% of controls. The telomeric gene is
      either lacking or interrupted in 226 of 229 patients, and patients retaining this
      gene (3 of 229) carry either a point mutation (Y272C) or short deletions in the
      consensus splice sites of introns 6 and 7. These data suggest that this gene,
      termed the survival motor neuron (SMN) gene, is an SMA-determining gene.

PMID- 7813014
TI  - Xenopus chordin and Drosophila short gastrulation genes encode homologous
      proteins functioning in dorsal-ventral axis formation.

PMID- 7813013
TI  - The gene for neuronal apoptosis inhibitory protein is partially deleted in
      individuals with spinal muscular atrophy.
AB  - The spinal muscular atrophies (SMAs), characterized by spinal cord motor neuron
      depletion, are among the most common autosomal recessive disorders. One model of
      SMA pathogenesis invokes an inappropriate persistence of normally occurring motor
      neuron apoptosis. Consistent with this hypothesis, the novel gene for neuronal
      apoptosis inhibitory protein (NAIP) has been mapped to the SMA region of
      chromosome 5q13.1 and is homologous with baculoviral apoptosis inhibitor
      proteins. The two first coding exons of this gene are deleted in approximately
      67% of type I SMA chromosomes compared with 2% of non-SMA chromosomes.
      Furthermore, RT-PCR analysis reveals internally deleted and mutated forms of the
      NAIP transcript in type I SMA individuals and not in unaffected individuals.
      These findings suggest that mutations in the NAIP locus may lead to a failure of
      a normally occurring inhibition of motor neuron apoptosis resulting in or
      contributing to the SMA phenotype.

PMID- 7813015
TI  - Different forms of TFIIH for transcription and DNA repair: holo-TFIIH and a
      nucleotide excision repairosome.
AB  - Yeast TFIIH that is active in transcription can be dissociated into three
      components: a 5-subunit core, the SSL2 gene product, and a complex of 47 kDa, 45
      kDa, and 33 kDa polypeptides that possesses protein kinase activity directed
      towards the C-terminal repeat domain of RNA polymerase II. These three components
      can reconstitute fully functional TFIIH, and all three are required for
      transcription in vitro. By contrast, TFIIH that is highly active in nucleotide
      excision repair (NER) lacks the kinase complex and instead contains the products
      of all other genes known to be required for NER in yeast: RAD1, RAD2, RAD4,
      RAD10, and RAD14. This repairosome is not active in reconstituted transcription
      in vitro and is significantly more active than any of the constituent
      polypeptides in correcting defective repair in extracts from strains mutated in
      NER genes.

PMID- 7813016
TI  - DNA polymerase epsilon links the DNA replication machinery to the S phase
      checkpoint.
AB  - Inhibition of DNA synthesis induces transcription of DNA damage-inducible genes
      and prevents mitotic entry through the action of the S phase checkpoint. We have
      isolated a mutant, dun2, defective for both of these responses. DUN2 is identical
      to POL2, encoding DNA polymerase epsilon (pol epsilon). Unlike sad1 mutants
      defective for multiple cell cycle checkpoints, pol2 mutants are defective only
      for the S phase checkpoint and the activation of DUN1 kinase necessary for the
      transcriptional response to damage. Interallelic complementation and mutation
      analysis indicate that pol epsilon contains two separable essential domains, an N
      terminal polymerase domain and a C-terminal checkpoint domain unique to epsilon
      polymerases. We propose that DNA pol epsilon acts as a sensor of DNA replication
      that coordinates the transcriptional and cell cycle responses to replication
      blocks.

PMID- 7813017
TI  - Autoregulatory frameshifting in decoding mammalian ornithine decarboxylase
      antizyme.
AB  - Rat antizyme gene expression requires programmed, ribosomal frameshifting. A
      novel autoregulatory mechanism enables modulation of frameshifting according to
      the cellular concentration of polyamines. Antizyme binds to, and destabilizes,
      ornithine decarboxylase, a key enzyme in polyamine synthesis. Rapid degradation
      ensues, thus completing a regulatory circuit. In vitro experiments with a fusion
      construct using reticulocyte lysates demonstrate polyamine-dependent expression
      with a frameshift efficiency of 19% at the optimal concentration of spermidine.
      The frameshift is +1 and occurs at the codon just preceding the terminator of the
      initiating frame. Both the termination codon of the initiating frame and a
      pseudoknot downstream in the mRNA have a stimulatory effect. The shift site
      sequence, UCC-UGA-U, is not similar to other known frameshift sites. The
      mechanism does not seem to involve re-pairing of peptidyl-tRNA in the new frame
      but rather reading or occlusion of a fourth base.

PMID- 7813018
TI  - The topology of the kinetoplast DNA network.
AB  - Kinetoplast DNA (kDNA) of trypanosomatid parasites is a network of approximately
      5000 catenated DNA minicircles and approximately 25 maxicircles. We developed the
      following strategy to deduce the topological linkage of the minicircles of the
      Crithidia fasciculata network. First, we used graph theory to provide precise
      models of possible network structures. Second, on the basis of these models, we
      predicted the frequencies of minicircle oligomers expected from random network
      breakage. Third, we determined the fragmentation pattern of kDNA networks as a
      function of the extent of digestion. Fourth, by comparison of the results with
      the predictions, we identified the model that best represents the network. We
      conclude that each minicircle is linked on average to three other minicircles. A
      honeycomb arrangement probably results, with each minicircle typically at the
      vertex of a hexagonal cell. This topology has implications for the assembly,
      structure, and function of kDNA networks.

PMID- 7813019
TI  - Escape from "horror autotoxicus": pathogenesis and treatment of autoimmune
      disease.

PMID- 7813020
TI  - xol-1 acts as an early switch in the C. elegans male/hermaphrodite decision.
AB  - xol-1 is the earliest-acting gene in the known hierarchy that controls C. elegans
      sex determination and dosage compensation. We show that the primary sex
      determining signal (the X/A ratio) directs the choice of sexual fate by
      regulating xol-1 transcript levels: high xol-1 expression during gastrulation
      triggers male development, whereas low expression at that time permits
      hermaphrodite development. Inappropriately high xol-1 expression causes
      hermaphrodites to activate the male program of development and die from a
      disruption in dosage compensation. These results demonstrate that xol-1 functions
      as an early developmental switch to set the choice of sexual fate and suggest
      that assessment of the X/A ratio occurs only early in embryogenesis to determine
      sex. Moreover, sdc-2, a gene that must be repressed by xol-1 to ensure male
      development, may be a direct target of negative regulation by xol-1.

PMID- 7813021
TI  - Stem cell patterning and fate in human epidermis.
AB  - Within human epidermis there are two types of proliferating keratinocyte: stem
      cells, which have high proliferative potential, and transit-amplifying cells,
      which are destined to undergo terminal differentiation after a few rounds of
      division. We show that, in vivo, stem cells express higher levels of the alpha 2
      beta 1 and alpha 3 beta 1 integrins than transit-amplifying cells and that this
      can be used both to determine the location of stem cells within the epidermis and
      to isolate them directly from the tissue. The distribution of stem cells and
      transit-amplifying cells is not random: patches of integrin-bright and integrin
      dull cells have a specific location with respect to the epidermal-dermal junction
      that varies between body sites and that correlates with the distribution of S
      phase cells. Stem cell patterning can be recreated in culture, in the absence of
      dermis, and appears to be subject to autoregulation.

PMID- 7813022
TI  - Control of neuronal diversity by the floor plate: contact-mediated induction of
      midbrain dopaminergic neurons.
AB  - The notochord and floor plate contribute to patterning the ventral neural tube in
      part by expressing a diffusible factor that induces motoneurons. To determine the
      mechanisms that direct the development of other classes of ventral neurons, we
      studied the development of dopaminergic neurons that reside near motoneurons in
      the ventral midbrain. We provide evidence that dopaminergic neurons develop in
      the vicinity of the floor plate and that they can be specified by the floor plate
      in vitro and in vivo. Unlike motoneurons, efficient induction of dopaminergic
      neurons requires contact with floor plate cells. These results suggest that
      neuronal diversification along the dorsal-ventral axis may be achieved partly
      through the concerted action of diffusible and contact-dependent signals from a
      single organizing center, the floor plate.

PMID- 7813023
TI  - Ischemia and infarction of the jaws--the "phantom" pain of NICO.

PMID- 7813024
TI  - Health-care reform--a paradigm shift.

PMID- 7813025
TI  - The relationship between temporomandibular joint mobility and peripheral joint
      mobility reconsidered.
AB  - The purpose of this paper was to study the relationship between temporomandibular
      joint (TMJ) mobility and mobility of joints and to study the general character of
      joint mobility in 83 subjects, 55 females and 28 males (mean age 26.7, range 13
      46 years). The subjects were recruited from the Department of Oral and
      Maxillofacial Surgery of the University Hospital of Groningen. All participants
      had a good general health and did not present anamnestically, clinically or
      radiographically TMJ disorders. Of these subjects, angular displacement of the
      mandible relative to the cranium during maximal mouth opening (AMO) was measured.
      Furthermore, the maximal range of motion of passive digit five hyperextension,
      passive thumb apposition to the wrist, active elbow and knee hyperextension,
      active ankle dorsal flexion and trunk flexion were measured. All measurements
      were performed bilaterally, except trunk flexion. Calculation of product moment
      correlations (Pearson) revealed a weak relationship between AMO and mobility of
      right digit five and elbows for the total group and between AMO and mobility of
      both digits five and elbows for women. The correlations were never stronger than
      0.4. Multiple regression revealed that only 25.9% of the total variance of AMO
      could be explained by mobility of peripheral joints, age and sex. Calculation of
      product moment correlations between mobility of peripheral joints, trunk flexion
      and age revealed weak correlations between the different joints, with the
      exception of paired joints. Principal component analysis revealed a weak general
      character of joint mobility.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7813027
TI  - Relationship between sagittal condylar path and the degree of mandibular
      asymmetry in unilateral cross-bite patients.
AB  - This study was conducted to investigate the relationship between sagittal
      condylar path and the degree of mandibular asymmetry during jaw opening movement
      in subjects (25 adults: 7 males, 18 females) with unilateral cross-bite. The
      degree of mandibular shift was measured with the axial projected head plate.
      Sagittal condylar path was obtained by CADIAX. The shifted side of the condyles
      had a steeper condylar path than that observed on the ipsilateral side. There was
      no correlation between the deviation of the forward component in the sagittal
      condylar path and the degree of mandibular asymmetry.

PMID- 7813026
TI  - Recording orthopedic jaw movements. Part IV: The rotational component during
      mastication.
AB  - The recording and analysis of mastication provides information on neuromuscular
      engrams, and hence avoidance mechanisms. Avoidance mechanisms are pathologic
      movement patterns which are developed to avoid occlusal interferences during
      functional movements. Evaluation of hinge-axis rotation permits selective
      quantitative analysis of a complex movement pattern. The objective of this study
      was to determine the amount of hinge axis rotation in mastication using
      computerized axiography. Furthermore, the distance of the condyles from reference
      position (RP) at maximum rotation was evaluated and the chronological sequence of
      translation and rotation was investigated. The mean value for the rotational
      angle of the mandible (gamma) during mastication was 14.1 degrees in the
      volunteers and 13.44 degrees in the patients. The linear spatial distance from RP
      amounted to a mean of 6.57 mm on the right side and 6.21 mm on the left in the
      volunteers. In the patients, the measurements were 6.33 mm on the right side and
      6.7 mm on the left. In most cases, maximum rotation did not correspond with
      maximum translation. The chronological sequence of maximum excursion was not
      constant.

PMID- 7813028
TI  - The use of magnetic resonance imaging to determine splint position in the
      management of internal derangements of the temporomandibular joint.
AB  - Internal derangements of the temporomandibular joint (TMJ) can elicit symptoms of
      pain, clicking and noises described subjectively as popping, grinding or grating.
      These symptoms may be the precursor of a more severe disease process such as
      degenerative joint disease (DJD) or osteoarthritis. The most common factor
      predisposing to degenerative changes within the TMJ is a displaced meniscus.
      Maintenance of a proper anatomic meniscal-condylar relationship is essential in
      preventing DJD. In the past, non-surgical treatment utilizing intraoral orthotic
      devices has been attempted to "recapture" the meniscus. The position of the
      meniscus was then evaluated merely by clinical examination due to the lack of
      modalities available to verify the meniscal position. The advent of magnetic
      resonance imaging (MRI) has changed this scenario. The meniscal position can now
      be visualized, thus enabling the practitioner to treat patients more effectively.
      Three case reports are presented in this study demonstrating the use of splint
      therapy utilizing MRI to determine meniscal position.

PMID- 7813029
TI  - Temporomandibular joint space analysis.
AB  - Radiographic interpretation of the temporomandibular joint (TMJ) frequently
      revolves around a determination of condyle concentricity. The purpose of this
      study was to establish the relationship between actual and radiographic joint
      space, the latter determined from lateral corrected tomograms made by a Soredex
      Scanora. Vacuum-formed shims were placed over the condylar heads of a human skull
      and tomographic images of the TMJs were made. These shims were measured using a
      caliper and the mean thickness was used to represent actual joint space.
      Thickness of the shims fabricated for the right condyle varied from .15 mm (1
      shim) to 1.60 mm (5 shims). The resulting radiographs were measured to determine
      the extent to which actual and radiographic joint space compared.

PMID- 7813030
TI  - A retrospective study on the clinical results of temporomandibular joint surgery.
AB  - A retrospective study on the results of temporomandibular joint (TMJ) surgery was
      performed in 74 patients with total menisectomy, 90 patients with partial
      menisectomy with disk repair, and 66 patients with arthroscopic lysis of adhesion
      and lavage of the joint space. TMJ pain during jaw movement, TMJ noise and
      maximum jaw opening was evaluated one year after surgery. TMJ pain and TMJ noise
      were significantly reduced by all three procedures. However, TMJ clicking was
      more significantly observed in patients with arthroscopy. Maximum jaw opening was
      significantly increased by all three procedures. However, maximum opening of
      patients with total menisectomy was significantly smaller than in the other two
      procedures.

PMID- 7813031
TI  - Evidence for construct validity of the TMJ scale in a sample of chronic post
      traumatic headache patients.
AB  - The construct validity of the TMJ Scale was examined in a sample of chronic post
      traumatic headache patients. Clinical indicators of temporomandibular (TM)
      dysfunction and measures of psychosocial distress were compared with relevant
      scales of the TMJ Scale. The clinical indicators were first subjected to
      principal components analysis. The resulting factor scores correlated
      significantly with selected physical domain scales of the TMJ Scale. The factor
      scores also significantly predicted the TMJ Global Scale in a regression
      analysis. Selected psychosocial domain scales of the TMJ Scale correlated
      strongly with measures of depression and anger and a clinical diagnosis of post
      traumatic stress disorder. The results support the validity of the TMJ Scale and
      demonstrates its utility with post-traumatic headache patients.

PMID- 7813032
TI  - Scientific Methodology in temporomandibular disorders. Part II: ethology.
AB  - The historical background of ethology and the paradigm of clinical treatment as
      scientific experiment, rather than practice of the art of dentistry are
      discussed. Ethology is defined and explained relative to the study of
      temporomandibular disorders (TMDs) using instrumentation, measurement and
      retrospective clinical studies of successfully treated cases as meaningful
      research for improvement of future treatment.

PMID- 7813033
TI  - The misdiagnosis of temporomandibular disorders in lateral pharyngeal space
      infections--two case reports.
AB  - Two cases of lateral pharyngeal space infections which were initially
      misdiagnosed as temporomandibular disorders (TMD) are presented and discussed.
      Such symptomatology as chronic facial pain, trismus and decreased inter-incisal
      opening provide many viable different diagnoses. It is important for the
      clinician to evaluate these different diagnoses in a logical manner. Conservative
      therapy is advised in the initial treatment of many TMDs, therefore other
      diagnoses with a greater potential for morbidity should be ruled in or out before
      the diagnosis of TMD is considered. The symptomatology of lateral space
      infections and the relevance of this entity to clinical dentistry are discussed.

PMID- 7813034
TI  - Tardive dyskinesia affected by occlusal treatment--a case report.
AB  - The following is a case report of occlusal treatment for involuntary mandibular
      movement occurring in a 79-year old woman. This was diagnosed as sulpiride
      induced tardive dyskinesia. The patient had been treated with sulpiride to
      improve gastrointestinal symptoms for five years until the onset of involuntary
      mandibular movement. The involuntary movement worsened even after discontinuation
      of the drug for 10 weeks. The dyskinesia improved in the course of treatment with
      an occlusal splint placed over her upper denture. After wearing the new denture
      with increased occlusal vertical dimension, the dyskinesia disappeared almost
      completely. Sirognathographic observation showed that previous denture wear
      evoked remarkable involuntary movement of the mandible once again. It is
      uncertain whether such improvement may result from discontinuation of the drug or
      from the occlusal treatment. However, it appears that occlusal factors played an
      important role in orofacial manifestation of tardive dyskinesia (TD) in this
      case.

PMID- 7813035
TI  - Mandatory benefits for TMD in twelve states.

PMID- 7813036
TI  - TMD support for doctors and patients.

PMID- 7813037
TI  - The correlation between cortical neuron maturation and neurofilament
      phosphorylation: a developmental study of phosphorylated 200 kDa neurofilament
      protein in cat visual cortex.
AB  - Neurofilament proteins are major constituents of the neuronal cytoskeleton. When
      phosphorylated, neurofilament proteins are thought to be involved in slowing down
      the slower component of axonal transport, thereby increasing neurofilament
      stability and conferring resistance to proteolysis. In order to investigate the
      correlation between phosphorylated neurofilament and plasticity of the cat visual
      cortex, we applied a monoclonal antibody, which recognizes only the
      phosphorylated form of neurofilament protein, to kitten visual cortex. This
      antibody appeared to recognize only axons. There was a progressive increase of
      phosphorylated neurofilament-immunoreactive axons in the cortical layers and
      white matter during development. In the visual cortex of young kittens,
      phosphorylated neurofilament immunoreactive processes were mostly long, fine, and
      continuous axons. However, in kittens older than 2 months of age, phosphorylated
      neurofilament immunoreactivity was characterized by short, punctae-like staining.
      The immunoreactive axons were most dense in deep cortical layers V and VI
      initially, followed at later ages by layers IVa and IVb, and finally in layer IVc
      and in the superficial cortical layers of adult animals. This developmental
      laminar pattern of distribution was not affected by early input restriction and
      coincides with electrophysiological evidence of early neuronal maturation. In
      addition, the phosphorylated neurofilament immunoreactivity can also be found in
      the dendrites and perikaya of degenerating neurons. These results suggest that
      phosphorylated neurofilament can be used as an index of functional maturity in
      the kitten visual cortex and also as a marker for neurodegeneration.

PMID- 7813038
TI  - Blockade of N-methyl-D-aspartate receptors by MK-801 (dizocilpine maleate)
      rescues motoneurones in developing rats.
AB  - In rats following nerve injury at birth a large proportion of motoneurones to the
      soleus muscle dies. Blocking of N-methyl-D-aspartate (NMDA) receptors by MK-801
      (dizocilpine maleate) for 12 days after nerve injury at birth leads to rescue of
      a proportion of motoneurones destined to die. Retrograde labelling of soleus
      motoneurones shows that 6-8 weeks after crushing the sciatic nerve in one
      hindlimb, only 10.9 +/- 2.3% of the motoneurones have survived. In animals
      treated with an NMDA receptor blocker MK-801 (2 mg/kg i.p., from birth to 12 days
      old) 50.6 +/- 3.8% of soleus motoneurones survived. This neuroprotective effect
      of MK-801 was dose dependant, since after treatment with lower doses (0.5 mg/kg;
      1 mg/kg) fewer motoneurones survived (13.7% and 34.5%, respectively). To assess
      the effect of treatment with MK-801 on survival of alpha-motoneurones only, the
      number of soleus motor units was established physiologically. After nerve injury
      alone only 4.2 +/- 1.2 of the 29-30 soleus motor units were present, while in
      animals treated with MK-801 (2 mg/kg) 14 +/- 1.5 motor units were identified. The
      neuroprotective effect of MK-801 was not confined to soleus motoneurones but was
      also apparent on motoneurones to the extensor digitorum longus (EDL). In
      untreated EDL muscles of the 40 motor units only 5.5 +/- 1.7 motor units survived
      neonatal nerve injury and this number increased to 18 +/- 2.6 after treatment
      with MK-801. The neuroprotective effect of MK-801 was apparent regardless of
      whether the nerve lesion was carried out close to or far from the soleus muscle.

PMID- 7813039
TI  - Protein ubiquitination and neuronal differentiation in chick embryos.
AB  - Ubiquitin is a small highly conserved intracellular protein which is involved in
      a number of cellular functions including targeting proteins for degradation. We
      have studied the distribution of ubiquitin-protein conjugates and two enzymes
      involved in protein ubiquitination in chick embryos. Using immunocytochemical
      techniques, we have observed that chick neural crest cells and dorsal root
      ganglia acquire immunoreactivity in their nuclei and cytoplasm as they mature,
      both in vivo and in vitro, though they are not immunoreactive at early stages of
      development. Immunoreactivity for the ubiquitin activating enzyme (E1) and a
      carboxyl terminal hydrolase for ubiquitin (PGP 9.5) also appears in the nuclei of
      differentiating neurons at the same time as ubiquitin-protein conjugates. Our
      results provide evidence that the nuclear accumulation of ubiquitin-protein
      conjugates is closely associated with maturation of neurons towards a
      differentiated phenotype.

PMID- 7813041
TI  - Chronic neonatal phencyclidine treatment produces age-related changes in
      pentylenetetrazol-induced seizures.
AB  - Although excitatory amino acids are known to play a critical role in the
      plasticity of developing brain, the behavioral effects of blocking the N-methyl-D
      aspartate (NMDA) receptor-gated ion channel during development are not clear.
      Here we report the effects of chronic postnatal administration of 1
      phenylcyclohexylpiperidine (phencyclidine or PCP), a NMDA channel blocker, on
      seizure susceptibility. To study the short-term effects of chronic PCP
      administration on pentylenetetrazol (PTZ)-induced seizures, rats were treated
      with PCP (5 mg/kg, i.p.) for 11 days from postnatal days 5-15, 24-34 or 44-54 and
      tested in the PTZ-induced seizure paradigm on postnatal days 21, 40 and 60,
      respectively. Administration of PCP in 5-15-day-old rats resulted in increased
      seizure susceptibility at day 21, while administration of PCP in postweanling
      rats (days 24-34) markedly attenuated their susceptibility to seizures at day 40.
      PCP injection had little effect on the seizure susceptibility of older rats. To
      study the long-term effects of postnatal PCP treatment, rats were injected with
      PCP (5 mg/kg from postnatal day 5-15, i.p.) and were tested for PTZ-induced
      seizures on postnatal days 40 and 60; each rat was tested only once. When tested
      for PTZ-induced seizure on day 40, PCP-treated rats did not differ from saline
      treated controls. When tested on day 60, PCP-treated rats had a lower incidence
      of seizures and in the rats that did have seizures their latencies were
      significantly prolonged compared to controls. Together, our data suggest that
      chronic PCP administration alters PTZ-induced seizure susceptibility in an age
      dependent manner and chronic PCP administration in postnatal rats produces long
      term changes that persist into adulthood.

PMID- 7813040
TI  - The arrest of luteinizing hormone-releasing hormone neuronal migration in the
      genetic arhinencephalic mouse embryo (Pdn/Pdn).
AB  - From previous observations, it was suggested that non-attachment of the olfactory
      nerve to the telencephalon blocked the induction of the olfactory bulbs in
      genetic arhinencephalic mouse embryos (Pdn/Pdn). The olfactory nerve ends in a
      tangle beneath the forebrain in these embryos. From these observations, we
      speculated that the migration of luteinizing hormone-releasing hormone (LHRH)
      neurons might be disturbed in the olfactory nerve. A mass of LHRH neurons was
      observed in the end of the olfactory nerve fibers, but LHRH neurons were found in
      the hypothalamus in Pdn/Pdn embryos on day 16 of gestation. Narrow by-paths were
      found between the olfactory nerve and the forebrain, and the migration of LHRH
      neurons through these by-paths was observed in Pdn/Pdn embryos on day 13 of
      gestation. From the reports that a gene deleted in the arhinencephalic syndrome
      (Kallmann's syndrome) shares homology with neural cell adhesion molecules (N
      CAM), it was speculated that non-attachment of the olfactory nerve in the Pdn/Pdn
      embryo might be associated with abnormalities of N-CAM. The axon fibers of the
      olfactory nerve reacted specifically with anti-N-CAM IgG both in +/- (+/+ and/or
      Pdn/+) and Pdn/Pdn on day 11.5 and 12, but not on day 13 and 16 of gestation. The
      axon fibers of the olfactory nerve were positive to anti-N-CAM IgG specifically
      just during the developmental period that the olfactory nerve fibers attached to
      the telencephalon. It is still not clear whether non-attachment of the olfactory
      nerve may be associated with N-CAM or not from the present observations.

PMID- 7813043
TI  - High potassium and cyclic AMP analog promote neuronal survival of basal forebrain
      cholinergic neurons in culture from postnatal 2-week-old rats.
AB  - We found depolarization-dependent promotion of survival of cultured basal
      forebrain cholinergic neurons from postnatal 2-week-old rats. Over 30 mM KCl
      (high K+) as well as nerve growth factor (NGF) induced considerably high choline
      acetyltransferase (ChAT) activity and the increase was potentiated by the
      addition of BAY K8644, a Ca2+ channel agonist. The increase in ChAT activity by
      high K+ was due to the increased number of viable acetylcholinesterase-positive
      and ChAT-positive neurons. Also, a cyclic AMP analog gave the same effect as high
      K+, but its ability to induce the ChAT activity was higher than that of high K+.
      On the other hand, both high K+ and NGF had very little effects on the survival
      of the cultured cholinergic neurons from 10-week-old rats. Cyclic AMP analog
      induced considerable increase in ChAT activity and promotion of survival of
      cholinergic neurons in the 10-week-old culture. These findings showed that the
      neuronal death occurring just of the end of synapse formation in rat basal
      forebrain cholinergic neurons could be prevented by NGF and high K+, but the
      death of older cholinergic neurons could not. We propose the possibility that the
      death of postnatal 2-week-old basal forebrain cholinergic neurons in culture
      might be programmed cell death.

PMID- 7813042
TI  - The development of neurotrophin receptor Trk immunoreactivity in the retina of
      the zebrafish (Brachydanio rerio).
AB  - The purpose of this study was to examine the cellular distribution of the Trk
      family of neurotrophin receptors in the retina and optic nerve of the zebrafish
      (Brachydanio rerio) during embryonic development. Semithin sections from
      zebrafish retinae were examined immunohistochemically for the presence of Trk
      polypeptides using commercially available antisera that cross-react with the
      fish. Cross-reactivity was confirmed by Western blot. Trk polypeptides were
      detected at about 1 day of age on the surfaces of retinal neuroblasts and faint
      Trk immunoreactivity was observed in the primordial optic nerve at 1.5 days. By 2
      days the optic nerve was clearly positive for Trk and at 2.5 days Trk
      immunoreactivity was found in the outer plexiform, inner nuclear, inner plexiform
      and ganglion cell layers, as well as in the optic nerve. At 3 days and 4 days the
      location of Trk immunoreactivity was unchanged but by 4 days it had diminished in
      intensity. In the adult zebrafish retina Trk immunoreactivity was found in the
      same locations as in the embryonic fish, as well as in a population of cells in
      the middle of the inner nuclear layer and in photoreceptors. We conclude that Trk
      neurotrophin receptors are present in the zebrafish eye during development and
      that their persistence in the adult may support the continuous neural
      reorganization that accompanies the growth of the eye in the fish.

PMID- 7813044
TI  - Postnatal development of the vasopressinergic system in golden hamsters.
AB  - Adult golden hamsters, as compared to rats, lack several parvicellular
      vasopressinergic cell groups. We looked at the development of the
      vasopressinergic system in hamsters to draw comparisons with maturing rats.
      Arginine-vasopressin-immunoreactive (AVP-ir) neurons, their fibers and associated
      AVP binding sites were observed at several intervals after birth. Different rates
      of maturation were observed between different populations of vasopressinergic
      neurons. Within the suprachiasmatic nucleus (SCN), small AVP-ir neurons, their
      fibers and related binding sites maturated gradually during the first month after
      birth. In comparison, large AVP-ir neurons were apparent in newborn animals.
      Similarly, AVP-ir fibers and AVP binding sites were also present in the brain of
      newborns within areas not related to small vasopressinergic neurons from the SCN,
      such as the central amygdala (CeA) or the cerebral cortex. During the following
      weeks, a heterogenous pattern of development was observed within such areas. As
      the neurosecretory vasopressinergic system appeared to develop gradually,
      projections to the brain and their associated binding sites developed rapidly
      during the first week of life. Transient patterns of maturation were observed
      within certain sites. Indeed, some of the labelling observed in newborns
      regressed later. As similar reports were made in rats, our observations draw
      analogies between the vasopressinergic systems of these two species, beside their
      apparent dissimilarities in adult animals. Furthermore, our data also reinforce
      the concept that large vasopressinergic neurons do not constitute a homogenous
      population.

PMID- 7813045
TI  - Developmental change of alpha-spectrin mRNA in the rat brain.
AB  - Spectrin is a cytoskeletal protein considered to be a major component of
      intracellular cohesion. Using an in situ hybridization approach, we have
      investigated the developmental expression of the mRNA encoding the alpha-subunit
      of rat brain spectrins, from birth to adulthood. alpha-Subunit mRNA is detectable
      at birth, in brain areas with perinatal neurogenesis, such as the cerebral
      cortex, hippocampus, thalamus, and olfactory bulb. alpha-Brain-spectrin mRNA
      increases gradually during the first postnatal days to reach a plateau between
      the second and the third week of life. In the young adult brain, the level of
      alpha-brain spectrin mRNA decreased globally. This spacio-temporal distribution
      argues for the involvement of the mRNA in the synthesis of both the erythroid and
      non-erythroid brain spectrin isoforms. We have focused our attention on the
      hippocampal formation and the cerebellum. In both regions, in situ hybridization
      signal variations are superimposable with neuronal maturation gradients. This
      pattern of variation, coupled with the known interaction of brain spectrins with
      other cytoskeletal proteins, agrees with the notion that brain spectrins may be
      involved in neuronal differentiation by way of the cytoskeletal lattice
      organization.

PMID- 7813046
TI  - The development of parvalbumin-immunoreactivity in the neocortex of the mouse.
AB  - In the present study the postnatal development of parvalbumin-immunoreactivity
      was examined in the neocortex of the mouse. Postnatal mice were processed at
      different developmental stages using a well-characterized monoclonal antibody
      against parvalbumin, and immunocytochemistry. The first immunoreactive neurons
      appeared in the first parietal and retrosplenial cortices at postnatal day 10
      (P10). From P11 to P12, immunoreactivity emerged in the second parietal,
      cingular, frontal, hindlimb-forelimb, first temporal, primary and secondary
      occipital and gustatory cortices, and at P14, parvalbumin-positive cells were
      present in the remaining regions. In general, parvalbumin-immunoreactivity
      appeared first in the primary sensory/motor areas, and then in second
      sensory/motor or associative areas. The maturation of parvalbumin
      immunoreactivity, however, was a long-lasting process, which was not completed
      until adult stages. In all cortical regions, parvalbumin-immunoreactive cells
      were present first in layer V, from which immunoreactivity expanded to the upper
      and inner cortical layers at subsequent developmental stages. This pattern of
      maturation differed from the usual 'inside-out' gradient of neocortical
      neurogenesis and maturation. At the cellular level, parvalbumin-immunoreactivity
      appeared first in cell somata, and staining of dendrites and boutons was apparent
      two days later. From the second postnatal week onwards, an immunoreactive axonal
      system was observed in the neocortical white matter and the corpus callosum. We
      conclude that the emergence and maturation of parvalbumin-immunoreactivity in the
      mouse neocortex shows marked area-specific differences, but proceeds following a
      similar center-to-outside radial gradient. These features may reflect the
      acquisition of certain physiological properties by a subset of GABAergic
      inhibitory neurons.

PMID- 7813047
TI  - Developmental expression of a 56 kDa protein isolated from rat neocortex.
AB  - The expression of ALZ-50 immunoreactivity in the immature rat cortex was assessed
      using a variety of immunochemical techniques. The antigen recognized by ALZ-50
      was isolated using immunoaffinity column chromatography. Unlike the ALZ-50
      positive antigen found in the brains of people with Alzheimer's Disease (mol. wt.
      68 kDa), the principal antigen expressed in the immature rat had a molecular
      weight of 56 kDa. The temporal expression of ALZ-50-positive antigens was
      determined with immunoblotting techniques. The expression of the 56 kDa protein
      appeared during the last prenatal week, increased to a peak during the second
      postnatal week and waned in the third postnatal week. Immunohistochemically,
      neonatal cortex contained many ALZ-50-positive neurons in the cortical subplate
      and the intermediate zone and a smattering of neurons in the cortical plate. The
      temporal expression of the ALZ-50-positive 56 kDa antigen was similar to that for
      fetal tau (tau-1); however, the principal protein identified by the anti-tau-1
      antibody was considerably larger (being about 68-70 kDa). In contrast to ALZ-50,
      tau-1-immunoreactive elements were distributed in the subplate, the deep cortical
      plate, the intermediate zone and the subventricular zone. tau-1-positive axons
      passing through the superficial intermediate zone were conspicuous. Thus, the
      biochemical and anatomical evidence show that ALZ-50 and tau-1 recognize distinct
      proteins.

PMID- 7813048
TI  - Effects of insulin-like growth factors on organotypic cocultures of embryonic rat
      brainstem slices and skeletal muscle fibers.
AB  - Embryonic rat brainstem slices including the facial and hypoglossal motor nuclei
      were maintained in organotypic cocultures with explants of embryonic tongue or
      post-natal skeletal muscle for periods up to 3 weeks. Survival and
      differentiation of motoneurones were dependent both on the type of muscle explant
      and its position relative to the brainstem. Tongue explants induced a more
      important glial outgrowth, a motoneurone migration towards the muscle, earlier
      muscular contractions and a more complete neuronal and muscular differentiation.
      Since the foetal tongue contains IGF levels as high as foetal liver, these
      effects might be due in part to diffusion of IGF from the explanted muscle.
      Indeed, foetal liver explants or crude foetal liver extracts induced effects
      similar to those of tongue explants. These effects can be reproduced by addition
      of IGF-1 or IGF-2, or both, into the culture medium. Although IGF-1 and IGF-2 had
      similar effects, IGF-1 induced a more pronounced muscular differentiation and IGF
      2 promoted neuronal differentiation. Our results suggest that IGFs are good
      candidates as muscle-derived neurotrophic factors promoting survival and
      differentiation of rat cranial motoneurones. These results also stress the
      importance of neuroglial trophic interactions and target development.

PMID- 7813049
TI  - The development of the anterior commissure in normal and hypothyroid rats.
AB  - The development of axon number in the anterior commissure (AC) was analyzed in 39
      normal and 37 hypothyroid rats using conventional electron microscopy.
      Hypothyroid rats underwent antithyroid treatment with methimazole from embryonic
      day (E) 14 onwards, followed in a fraction of the animals by thyroidectomy at
      postnatal day (P) 6. In normal rats, the midsagittal cross-sectional anterior
      commissure area (ACA) increased throughout their life; in hypothyroid rats, ACA
      was stationary from P4 onwards and at P174-180 it was reduced by 39% relative to
      normal rats. In normal rats, the number of AC axons increased rapidly from
      168,500 at E18 to, on average, 1,049,000 from P4 onwards. Similarly, in
      hypothyroid rats, the number of axons increased from 135,000 at E18 to, on
      average, 1,052,000 from P4 onwards. At all ages, the number of axons was similar
      in normal and hypothyroid rats. During development of the AC, the evolution of
      axon number observed in normal and hypothyroid rats is different from what was
      reported for other telencephalic commissures, including the AC of the monkey,
      where an important fraction of the axons are eliminated postnatally. Antithyroid
      treatment dissociated ACA from total number of AC axons.

PMID- 7813050
TI  - Voltage-activated potassium currents in acutely dissociated hippocampal dentate
      gyrus neurons from neonatal rats.
AB  - We have studied outward currents of neurons acutely dissociated from the dentate
      gyrus region of hippocampus using whole-cell and perforated patch recordings.
      Depolarizing voltage commands activated sustained outward currents at all age
      tested (P5-P30). Outward currents were blocked by tetraethylammonium (10 mM) but
      not 4-aminopyridine (25 mM). Comparison of sustained potassium current during
      postnatal development showed a significant increase in current amplitude with age
      reaching a peak between P20 and P30. These results suggest an overall increase in
      the number of voltage-dependent ion channels during development, specifically
      those underlying TEA-sensitive potassium currents.

PMID- 7813051
TI  - Developmental changes in rat diaphragm endplate response to repetitive
      stimulation.
AB  - Endplate potentials (epps) were recorded intracellularly from single diaphragm
      fibers, in vitro, of newborn (< or = 10 days, n = 10) and older (18-29 days, n =
      5) rats with glass microelectrodes. The muscle was stimulated via the phrenic
      nerve for 1 s at 10, 20 or 50 Hz. Muscle action potentials were blocked by mu
      conotoxin GIIIA, a specific muscle Na+ channel blocker. In diaphragms from older
      animals, epps followed nerve stimulation at the 3 frequencies, with a gradual
      decrement in amplitude to 70% of the first epp at 50 Hz. The younger age group
      showed an initial enhancement of epp amplitude, followed by large variability in
      amplitude. These data suggest that neuromuscular transmission failure in the
      newborn diaphragm is secondary to variability in neurotransmitter release as
      compared to the more mature diaphragm.

PMID- 7813052
TI  - The stimulatory effect of brain-derived neurotrophic factor on dopaminergic
      phenotype expression of embryonic rat cortical neurons in vitro.
AB  - Cells of embryonic (E12-16) rat cerebral cortex were cultured for 7 days in vitro
      (7DIV) in the presence of either brain-derived neurotrophic factor (BDNF),
      ciliary neurotrophic factor (CNTF), with or without dopamine (DA). Chronic
      treatment of cells with DA or BDNF alone increased (300% and 600%, respectively)
      the number of the cells that expressed tyrosine hydroxylase (TH). However, the
      combination of BDNF and DA treatment greatly increased the expression of TH in
      E14 cortical cells in a dose-dependent manner, to a much greater extent than DA
      or BDNF alone. This marked response due to treatment with both BDNF and DA was
      greater in cortical tissue from E12 embryos than that from E14 embryos. The
      combination of CNTF and DA also increased expression of the dopaminergic
      phenotype whilst CNTF alone was ineffective, but this effect was largely due to
      DA. No effect of DA, or of neurotrophic factors, was observed on cortical cells
      from E16 embryos under any of the treatment conditions. The present study reveals
      how chemical environment plays an important role in determining the final
      phenotype of cortical neurons during early periods in brain development. BDNF,
      but not CNTF, may influence the differentiation of fetal cortical cells towards a
      dopaminergic phenotype via a unique mechanism, different from that due to DA.
      This combination of nerve growth factor and neurotransmitter may be of general
      importance in phenotype determination in the early developmental stages of the
      nervous system.

PMID- 7813053
TI  - Evidence for a tropic role of brain-derived neurotrophic factor in transplanted
      embryonic retinae.
AB  - Developing retinal axons must follow a stereotypic course directing them to the
      subcortical visual centres which on arrival they must recognise. Transplantation
      studies suggest that local substrate cues close to the surface of the brainstem
      and diffusible factors emanating from the target region are important. To test a
      role for diffusible factors, we transplanted retinae to the cerebral cortex and
      have shown that outgrowth can be promoted by BDNF secreting fibroblasts.

PMID- 7813054
TI  - Diagnosing disorders of fatty acid oxidation.

PMID- 7813055
TI  - Total porphyrin and coproporphyrin and uroporphyrin fractions in urine measured
      by second-derivative spectroscopy.
AB  - A second-derivative scan of an acidified urine sample allows the amplitude of
      deflection (delta A) and the minimum wavelength of the trough (lambda min) to
      determine the correct porphyrin concentration and the coproporphyrin:uroporphyrin
      (copro:uro) ratio, respectively, from a nomogram constructed from calibrator
      solutions. We measured 24 urine samples for total porphyrin as coproporphyrin
      equivalents and adjusted the results with factors from the nomogram. The adjusted
      results (x) (mean +/- SE, 501 +/- 57 nmol/L) compared favorably with the expected
      results (y) (514 +/- 57). The regression equation and correlation coefficient
      were: y = 0.993x - 8.9 (r = 0.998, S(y/x) = 16.2). Results of the copro:uro ratio
      derived by second-derivative spectroscopy and HPLC showed no significant
      difference (chi 2-test) from samples with various copro:uro ratios. Recovery
      studies on four urine samples supplemented with known proportions of
      coproporphyrins and uroporphyrins gave good agreement between the measured and
      the expected porphyrin ratios. The overall imprecision (CV) of the assay ranged
      from 3.6% to 6.0% for coproporphyrin and from 3.2% to 9.1% for uroporphyrin.

PMID- 7813056
TI  - D-lactic acidemia and aciduria in pediatric and adult patients with short bowel
      syndrome.
AB  - D-Lactate produced by abundant intestinal lactobacilli during acidotic episodes
      in short bowel (SB) patients is commonly regarded as a main factor in the
      pathogenesis of SB syndrome-associated (D-lactic) acidosis. Since we had observed
      that gram-positive bacteria, mainly lactobacilli, were abundant even in the
      absence of acidosis, we studied serum concentrations and urinary excretions of D-
      and L-lactate in young and adult SB patients, especially during nonacidotic
      periods. Serum L-lactate and urinary L-lactate excretion were similar in adults
      and children. Serum D-lactate and urinary D-lactate excretion were higher in SB
      children than in SB adults. Food consumption affects D-lactate production and
      alters D-lactic acidemia and aciduria. We conclude that D-lactate is frequently
      present in serum of SB patients even in the absence of acidosis. High serum
      concentrations and urinary excretions may reflect dietary factors in these
      patients.

PMID- 7813057
TI  - Increased hepatic secretion of very-low-density lipoprotein apolipoprotein B-100
      in cholesteryl ester storage disease.
AB  - Using a stable isotope method, we measured the hepatic secretion rate of very-low
      density lipoprotein apolipoprotein B-100 (VLDL apoB) in a 26-year-old women who
      had dyslipidemia due to cholesteryl ester storage disease (CESD) and in five
      normolipidemic subjects. [1-13C]Leucine was administered by a primed constant
      intravenous infusion and the enrichment of VLDL apoB was determined by gas
      chromatography-mass spectrometry. The absolute secretion rate (ASR) of VLDL apoB
      in the patient was more than twice the mean ASR of the normolipidemic group (17.1
      vs 8.0 +/- 0.8 mg/kg body wt. per day). The plasma mevalonic acid concentration,
      a measure of intrahepatic cholesterol synthesis, was also greater in the patient
      than in the normolipidemic subjects (8.3 vs 4.4 +/- 1.8 micrograms/L). The
      findings are consistent with the hypothesis that in CESD increased intrahepatic
      synthesis of cholesterol stimulates hepatic secretion of VLDL apoB and this may
      partly account for the dyslipidemia.

PMID- 7813058
TI  - False-positive immunoassay results for urine benzodiazepine in patients receiving
      oxaprozin (Daypro).

PMID- 7813059
TI  - Intrasubject variation of creatinine and specific gravity measurements in
      consecutive urine specimens of heroin users.

PMID- 7813060
TI  - Spuriously high concentration of serum free thyroxine due to anti
      triiodothyronine antibodies.

PMID- 7813061
TI  - Rapid assay of phospholipase A2 activity in plasma and synovial fluid.

PMID- 7813062
TI  - Investigating the cause of hirsutism and acne in women.

PMID- 7813063
TI  - European specifications for imprecision and inaccuracy compared with US CLIA
      proficiency-testing criteria.

PMID- 7813064
TI  - Failure of anti-lambda immunofixation reagent mimics alpha heavy-chain disease.

PMID- 7813065
TI  - Severe isopropanolemia without acetonemia: contamination of specimens during
      venipuncture?

PMID- 7813066
TI  - Was Paganini born with Ehlers-Danlos syndrome phenotype 4 or 3?

PMID- 7813067
TI  - Natural history and risk factors for early human atherogenesis. Pathobiological
      Determinants of Atherosclerosis in Youth (PDAY) Research Group.
AB  - A multi-institutional study, Pathobiological Determinants of Atherosclerosis in
      Youth (PDAY), was initiated to document the natural history of atherosclerosis,
      its relationship to risk factors, and the pathobiology of lesion development in
      young subjects. Pathology laboratories in nine centers collected arteries and
      tissues from > 2000 persons, ages 15-34 years, whose deaths were attributed to
      homicides, accidents, or suicides. Arteries were evaluated for lesions, and risk
      factors were analyzed in a central laboratory. Postmortem risk factors include
      serum lipoproteins, serum thiocyanate (smoking), glycohemoglobin (diabetes),
      thickness of panniculus adiposus (obesity), changes in small renal arteries
      (hypertension), and apoprotein isoforms. This PDAY study documents the
      development of atherosclerosis at an early age and shows that the recognized risk
      factors for coronary heart disease are associated with lesion development in the
      arteries of these young subjects. The findings provide a strong justification for
      reducing risk factors in young persons.

PMID- 7813068
TI  - Role of low-density lipoproteins in atherogenesis and development of coronary
      heart disease.
AB  - There is a strong association between increased blood concentrations of low
      density lipoprotein (LDL) and severity of coronary atherosclerosis. Multiple
      mechanisms affect hypercholesterolemia, e.g., diet, aging, hormones, and
      genetics. LDL receptors apparently are also important--through down-regulation,
      defects in structure, or decreased numbers--as are changes in LDL binding
      characteristics caused by alterations in apolipoprotein B content or structure.
      Current concepts of LDL metabolism are extensively reviewed, including the role
      of modified or oxidized LDL in atherogenesis.

PMID- 7813069
TI  - Does wine work?

PMID- 7813070
TI  - Clinical significance of lipoprotein size and risk for coronary atherosclerosis.
AB  - Correlation between coronary heart disease and lipoprotein size and composition
      is well documented. Within the low-density lipoprotein (LDL) family the small LDL
      particles are associated with increased risk of coronary heart disease. These
      particles also have increased apolipoprotein (apo) B content. The appearance of
      these small LDL particles is the manifestation of complex alteration of plasma
      lipoprotein metabolism. The LDL size is influenced by genetic, endocrine, and
      environmental factors. Within the high-density lipoprotein (HDL) family the
      decrease of larger HDL2 particles is associated with coronary heart disease. HDLs
      can also be separated according to their apoprotein composition into particles
      containing lipoprotein (Lp)A-I only and particles containing LpA-I and LpA-II.
      Most studies have shown that the concentration of LpA-I-only particles decreases
      in coronary heart disease. HDLs are remodeled in the circulation and this
      remodeling continues in vitro after the blood is taken. Therefore adequate
      preservation of blood samples is necessary.

PMID- 7813071
TI  - Atherogenic nature of triglycerides, postprandial lipidemia, and triglyceride
      rich remnant lipoproteins.
AB  - In addition to low-density lipoproteins, plasma chylomicrons and very-low-density
      lipoproteins (VLDL) contribute to atherogenesis. When triglyceride-rich particles
      bind to arterial endothelium and to deendothelialized areas, locally present
      lipoprotein lipase initiates triglyceride hydrolysis and decreases the size of
      the adhering particles. Additional changes in composition are brought about by
      the exchange of lipids between chylomicron/VLDL remnants and the cholesteryl
      ester-rich low- and high-density lipoproteins. These exchanges are mediated by
      lipid transfer proteins in plasma. Animal studies with doubly labeled
      lipoproteins show that the size of lipoprotein particles determines their rate of
      entering the artery and contributes to the formation of lesions. This model
      supports epidemiologic studies that have identified plasma triglycerides as a
      risk factor for atherogenesis. The model for a causal role of pre- and
      postprandial triglyceride-rich lipoproteins in atherogenesis suggests that
      measuring them may improve the assessment of cardiovascular risk factors.

PMID- 7813073
TI  - Relation of high-density lipoprotein subfractions and apolipoprotein E isoforms
      to coronary disease.
AB  - Although a variety of methods have become available for the determination of high
      density lipoprotein (HDL) subfractions in plasma, a review of published data from
      nine studies of coronary disease outcomes and 10 investigations of coronary
      artery disease severity do no suggest that measurement of HDL2-cholesterol (C)
      and HDL3-C offer any advantage in the prediction of coronary disease over the
      determination of total HDL-C alone. Apolipoprotein E is typically present in
      plasma as one of six isoforms, the six being encoded by three common alleles,
      epsilon 2, epsilon 3, and epsilon 4. The epsilon 3 allele is the most common, the
      epsilon 4 allele has been reported to be associated with higher cholesterol
      concentrations, and the epsilon 2 and epsilon 4 alleles are both associated with
      higher triglyceride concentrations. Clinical and arteriographic studies of
      coronary disease suggest that vascular disease risk is increased among persons
      with the epsilon 4 allele.

PMID- 7813072
TI  - Serum apolipoproteins A-I and B as markers of coronary artery disease risk in
      early life: the Bogalusa Heart Study.
AB  - The functional properties of the apolipoproteins (apoB and apoA-I) governing
      lipoprotein metabolism make these variables conceptually important as markers for
      coronary artery disease risk. This aspect was examined in a biracial (black
      white) population of children as part of the Bogalusa Heart Study. White
      children, especially boys, showed lower concentrations of apoA-I and ratios of
      cholesterol to apoB within low-density lipoprotein (LDL) than did black children.
      Persistence of apoB concentrations over time, coupled with its strong linkage
      with apoB gene locus, underscores the value of detecting apoB excess early in
      life. Further, the impact of apoE genotypes on apoB and apoA-I levels is already
      evident in childhood. We found that, as a screening test for detecting increased
      LDL cholesterol, apoB is superior to total cholesterol. Low values for apoA-I
      concentration, the apoA-I to apoB ratio, and LDL cholesterol to apoB ratio in
      children are strongly related to parental incidence of myocardial infarction; no
      such relationship is seen with respect to lipoprotein cholesterols. Thus,
      expanding screening strategies might be useful for identifying individuals with
      adverse apolipoprotein profiles early in life.

PMID- 7813074
TI  - Enhanced chemiluminescence labeled-antibody immunoassay (Amerlite-MAB) for free
      thyroxine: design, development, and technical validation.
AB  - We describe the development and validation of a one-step nonradioactive
      immunoassay for free thyroxine (Amerlite-MAB FT4) in serum or plasma, in the
      dedicated Amerlite enhanced luminescence assay system. A monoclonal antibody to
      thyroxine (T4), conjugated with horseradish peroxidase (HRP; EC 1.11.1.7),
      competes for binding with FT4 or with a conjugate of a protein and L
      triiodothyronine immobilized onto the surface of the assay microwells. The signal
      is generated by antibody-HRP bound to the protein-T3 conjugate, with luminol as
      substrate. The assay design exploits the high sensitivity of luminescence signal
      detection, permitting minimal sample dilution and T4 sampling by the antibody. It
      withstands progressive dilution of serum and is unaffected by T4-binding proteins
      in serum. The disclosure and validation of this FT4 assay follows guidelines
      recommended by the American Thyroid Association.

PMID- 7813075
TI  - Structural and functional polymorphism of lipoprotein(a): biological and clinical
      implications.
AB  - Lipoprotein(a) [Lp(a)], a variant of low-density lipoprotein, is heterogeneous in
      density because of variability in the content and composition of its core lipids
      and size polymorphism of its specific glycoprotein component, apolipoprotein(a)
      [apo(a)]. In some individuals, density polymorphism may also derive from the fact
      that Lp(a) contains 2 mol of apo(a) per mole of apoB100, contrary to the more
      common 1:1 molar stoichiometry. Moreover, the size of apo(a) is polymorphic
      because of variations in the number of kringle 4 type 2 repeats. Another type of
      apo(a) polymorphism is related to sequence mutations at the kringle level. Two
      mutations can occur in kringle 4 type 10: one, Trp72-->Arg, is affiliated with an
      Lp(a) that is lysine-binding defective; the other, Met66-->Thr, with a normal
      lysine-binding function. Thus, Lp(a) is structurally and functionally
      polymorphic, a notion that must be considered in assessing the cardiovascular
      pathogenicity of this lipoprotein variant and in immunoquantification assays.

PMID- 7813076
TI  - Plasma homocyst(e)ine and arterial occlusive diseases: a mini-review.
AB  - Homocysteine (HCY), which is derived from the intracellular metabolism of
      methionine, is exported into plasma, where it circulates mostly in oxidized forms
      (i.e., homocystine and cysteine-HCY disulfide) and mainly bound to proteins.
      Concentrations of total HCY, or homocyst(e)ine [H(e)], are increased in 15-40% of
      patients with coronary, cerebral, or peripheral arterial diseases. Such
      association of H(e) with arterial occlusive diseases has been documented in
      retrospective, cross-sectional, and prospective studies. Concentrations of H(e)
      are also increased in subjects having thickened carotid arteries, as determined
      by ultrasonography, and who are asymptomatic for atherosclerosis. Statistical
      analyses of data from several series of patients demonstrate that H(e)
      concentrations are associated with coronary artery disease, independently from
      most other risk factors for atherosclerosis. The increased concentrations of H(e)
      are readily corrected by folic acid, occasionally supplemented with pyridoxine,
      vitamin B12, choline, or betaine. Whether these supplements affect the evolution
      of atherosclerotic disease needs to be established by prospective, placebo
      controlled clinical trials.

PMID- 7813077
TI  - Multicenter evaluation of enhanced chemiluminescence labeled-antibody immunoassay
      (Amerlite-MAB) for free thyroxine.
AB  - The technical and diagnostic performance of the Amerlite-MAB enhanced
      luminescence assay for free thyroxine (FT4) was assessed in a multicenter
      evaluation trial. The euthyroid central 95% reference range for FT4 (1393
      subjects) was 11.5-27.7 pmol/L (by cumulative frequency plot with two-tailed 2.5%
      cutoffs). Results (y) agreed with those of similar radioactive method (Amerlex
      MAB FT4) (x): y = 1.06 x + 0.54, Sylx = 335.5, n = 235). Mean within-assay
      precision (CV) in six centers was 5.7% at 6 pmol/L and 2.6% at 51 pmol/L FT4;
      between-assay precision (CV) was 7.2% and 3.6%, respectively. Diagnostic
      performance was assessed in all patient groups usually encountered, including
      those with nonthyroidal illness and extreme binding-protein anomalies. In elderly
      euthyroid subjects, the proportion of above-normal FT4 values exceeded that in
      younger age-groups. These increases often accompanied normal estimates of
      thyrotropin and, in some cases, might have arisen by interference from medication
      that is taken more often by the elderly.

PMID- 7813078
TI  - Effect of red wine ingestion on the antioxidant capacity of serum.
AB  - Aerobic metabolism in biological systems produces reactive oxygen species, and
      defense against such prooxidants requires antioxidant activity, e.g.,
      predominantly vitamins C and E in serum. Recently, flavonoids (polyphenols
      occurring widely in plants) have been investigated in vitro for their antioxidant
      activity; whether they are absorbed after ingestion is not clear. Using a
      chemiluminescent assay of serum antioxidant capacity (SAOC), we have studied the
      effects in normal individuals of ingesting red wine, white wine, and high doses
      of vitamin C. In nine subjects who ingested 300 mL of red wine, the mean SAOC was
      increased by 18% after 1 h and by 11% at 2 h. The same amount of white wine
      produced 4% and 7% increases, respectively. The ingestion of 1000 mg (5.7 mmol)
      of ascorbic acid by four subjects increased their mean SAOC by 22% at 1 h and by
      29% at 2 h. An in vitro comparison of red wine, white wine, and various fruit
      juices showed the high antioxidant capacity of red wine in addition to its
      ability to increase the antioxidant capacity of serum in vivo. The antioxidant
      effects of various flavonoids and other polyphenols were also studied.

PMID- 7813079
TI  - Indirect estimation of thyroid hormone-binding proteins to calculate free
      thyroxine index: comparison of nonisotopic methods that use labeled thyroxine ("T
      uptake")
AB  - There are many alternative ways of estimating free thyroxine (T4) when
      thyrotropin screening results are abnormal. In addition to free T4 immunoassays,
      the menu of most automated immunoassay instruments includes a nonisotopic version
      of the original triiodothyronine (T3)-uptake assay called "T-uptake." We
      evaluated the ability of five such assays (Access, ES-300, IMx, Magnum Opus, and
      Stratus) to accurately estimate the free thyroxine index (FTI) in euthyroid,
      hyperthyroid, and hypothyroid patients with abnormal concentrations of thyroid
      hormone-binding proteins, and in patients with nonthyroidal illness. For
      comparison, we calculated a similar FTI, using either T3-uptake or direct
      measurement of thyroxine-binding globulin (TBG). Euthyroid reference ranges were
      comparable. Of euthyroid patients with increased TBG, 12-32% and 5-20% had
      increased or suppressed FTI, respectively, depending on the T-uptake method used.
      Except for IMx, 6-35% of hypothyroid patients with increased TBG had
      inappropriately increased FTI. Patients with nonthyroidal illness had comparable
      results regardless of the method used, and T-uptake methods were variably
      affected by known inhibitors of thyroid hormone binding. The most reliable T
      uptake method appeared to be the IMx, which, despite claims that it measures all
      thyroid hormone-binding proteins, correlated best with TBG concentrations.

PMID- 7813080
TI  - Estrogen and progesterone receptors in breast cancer microsamples simultaneously
      quantified by enzyme-ligand immunoassay.
AB  - A new method (enzyme-ligand immunoassay, ELIA) is described for the estimation of
      estrogen (ER) and progesterone (PR) receptors in microsamples of human breast
      cancer tissue. The technique, based on the nonisotopic measurement of receptor
      bound estradiol and progesterone, involves three steps: (a) simultaneous
      saturation of active receptors with their respective authentic ligands, (b) heat
      treatment of the cytosol to release the steroids from their cognate receptors
      before or after absorption with dextran-coated charcoal, and (c) measurement of
      both steroids present in the cytosol by a modified competitive-inhibition enzyme
      immunoassay. The useful range of the method was 10-4000 pmol/L for ER and 6.5
      1000 pmol/L for PR. The correlation coefficient (r) between the one-point and
      Scatchard plot analysis was 0.95 for ER and 0.99 for PR. Comparison of the one
      point ELIA and expected values with the radioligand binding assay (RLBA) results
      for EORTC samples gave r = 0.88 and 0.99 for ER and PR, respectively. Further
      comparison of the one-point ELIA with RLBA and with a commercial enzyme
      immunoassay, in blind testing of cancer tissue microsamples from 70 patients,
      gave good agreement for ER with r = 0.95-0.97 and concordance of 92.9-94.4%
      (cutoff, 15 pmol/g protein) against the other two methods. The results were more
      disperse in all three methods for PR estimation, the assay correlating perhaps
      better with the enzyme immunoassay (r = 0.90) at a concordance of 89.4% (same
      cutoff value).

PMID- 7813081
TI  - Finnish-type aspartylglucosaminuria detected by oligonucleotide ligation assay.
AB  - Aspartylglycosaminuria (AGU) is a recessively inherited lysosomal storage disease
      that occurs with much higher frequency in Finland than elsewhere. AGU is caused
      by a deficiency in glycosylasparaginase (GA), which results in the accumulation
      of glycoasparagines in lysosomes. In the Finnish population, a single nucleotide
      change in the gene encoding GA is responsible for the disease. We have used the
      oligonucleotide ligation assay (OLA) to detect the mutation in polymerase chain
      reaction (PCR)-amplified DNA samples from normal, carrier, and affected
      individuals. Screening for AGU among 415 random Finnish DNA samples with PCR/OLA
      revealed five carriers of the mutant allele and demonstrated the potential of the
      method for use in carrier screening. PCR/OLA provides a rapid, reliable,
      nonisotopic method to detect the mutation responsible for AGU that can readily be
      applied to large population screening.

PMID- 7813082
TI  - Rapid diagnosis of maple syrup urine disease in blood spots from newborns by
      tandem mass spectrometry.
AB  - We report a new method for the diagnosis of maple syrup urine disease (MSUD) from
      dried blood spots on newborn screening cards based on tandem mass spectrometry
      (MS-MS). The mean +/- SD concentration of Leu plus Ile in normal newborns was 151
      +/- 47 mumol/L (n = 1096); for Val, 131 +/- 58 mumol/L (n = 791). SDs were lower
      when the concentrations of these amino acids were expressed relative to that of
      Phe. The mean ratio for Leu + Ile to Phe was 2.5 +/- 0.49; for Val to Phe, 2.18
      +/- 0.51. These results compare well with values previously reported in the
      literature. With these criteria, samples from a collection categorized by a
      bacterial inhibition assay as normal or falsely positive for MSUD were normal by
      MS-MS [(Leu + Ile): Phe < 5.0]. Samples from confirmed MSUD patients were
      categorized as abnormal [(Leu+Ile): Phe > 9.0] by MS-MS.

PMID- 7813083
TI  - A molecular protocol for diagnosing myotonic dystrophy.
AB  - Myotonic dystrophy (DM) is an autosomal dominant genetic disease caused by an
      unstable CTG repeat sequence in the 3' untranslated region of the myotonin
      protein kinase gene. The CTG repeat is present 5-30 times in the normal
      population, whereas DM patients have CTG expansions of 50 to several thousand
      repeats. The age of onset of the disorder and the severity of the phenotype is
      roughly correlated with the size of the CTG expansion. We developed a molecular
      protocol for the diagnosis of DM based on an initial polymerase chain reaction
      screen to detect normal-sized alleles and small expansions, followed by an
      improved Southern protocol to detect larger expansions.

PMID- 7813084
TI  - Apolipoprotein E2/E3/E4 genotyping with agarose gels.
AB  - Here we report an improved, simple method to assign the human apolipoprotein
      (apo) E genotype and its isoforms, apo E2, apo E3, and apo E4. Genomic DNA was
      amplified with specific primers that included the polymorphic region of amino
      acids 112 and 158. Digestion of the product with Hhal resulted in unique
      fragments that were separated on Meta-Phor agarose instead of polyacrylamide. The
      pattern of unique DNA fragments obtained unequivocally characterizes the
      different apo E alleles.

PMID- 7813086
TI  - Standardization of glycohemoglobin results and reference values in whole blood
      studied in 103 laboratories using 20 methods.
AB  - We investigated the effect of calibration with lyophilized calibrators on whole
      blood glycohemoglobin (glyHb) results. One hundred three laboratories, using 20
      different methods, determined glyHb in two lyophilized calibrators and two whole
      blood samples. For whole-blood samples with low (5%) and high (9%) glyHb
      percentages, respectively, calibration decreased overall interlaboratory
      variation (CV) from 16% to 9% and from 11% to 6% and decreased intermethod
      variation from 14% to 6% and from 12% to 5%. Forty-seven laboratories, using 14
      different methods, determined mean glyHb percentages in self-selected groups of
      10 nondiabetic volunteers each. With calibration their overall mean (2SD) was
      5.0% (0.5%), very close to the 5.0% (0.3%) derived from the reference method used
      in the Diabetes Control and Complications Trial. In both experiments the Abbott
      IMx and Vision showed deviating results. We conclude that, irrespective of the
      analytical method used, calibration enables standardization of glyHb results,
      reference values, and interpretation criteria.

PMID- 7813085
TI  - Apolipoprotein AI, AII, and AIV isoforms in plasma determined by automated
      isoelectric focusing with PhastSystem and immunofixation.
AB  - Distinct genetic variants of apolipoprotein (apo) AI have been shown to influence
      concentrations of high-density lipoprotein (HDL) cholesterol. The genetic
      polymorphism of apo AIV may modulate HDL-cholesterol, plasma triglycerides, and
      lipoprotein(a) concentrations. There is evidence for an antagonizing role of apo
      AII in reverse cholesterol transport. Since genetic polymorphisms and variants of
      these apolipoproteins are detectable by isoelectric focusing (IEF), we developed
      a rapid and easy automated method for IEF analysis of apos AI, AII, and AIV on
      self-made or commercially available gels, using the PhastSystem. Diluted plasma
      or serum samples (1 microL) are applied automatically onto the gel and IEF is
      carried out for 35-45 min. Afterwards, the apo A bands are precipitated by
      specific polyclonal antibodies and visualized by automated silver staining. This
      rapid procedure is suitable as a routine or screening method for IEF analysis of
      these major HDL apolipoproteins.

PMID- 7813087
TI  - Solubility of silver sulfadiazine in physiological media and relevance to
      treatment of thermal burns with silver sulfadiazine cream.
AB  - Silver sulfadiazine cream has been a standard treatment for burns over the past
      two decades. Although many studies have described the phenomenon of silver
      absorption from burn wounds treated with silver sulfadiazine, they failed to
      examine the chemistry underlying the absorption process: Silver chloride was
      assumed to form at the burn wound and absorption of silver was believed to be
      negligible. Here we have developed chemical model systems to investigate the
      interactions of silver sulfadiazine and silver chloride in direct contact with
      synthetic serum electrolyte solution (SSES), with SSES plus endogenous ligands or
      beef blood plasma, and with human serum. The results indicate that silver
      absorption from an acute burn site can be significant, because human serum is
      capable of solubilizing silver. This finding is of concern, given the potential
      for silver toxicity as a direct consequence of applying silver sulfadiazine to
      extensive burn wounds.

PMID- 7813088
TI  - Cloned enzyme donor immunoassay (CEDIA) for drugs-of-abuse screening.
AB  - Large numbers of specimens (5000-18,000) were screened for amphetamines,
      barbiturates, cocaine, marijuana, opiates, and phencyclidine by RIA (Roche), Emit
      II (Syva), and a new immunoassay, CEDIA (cloned enzyme donor immunoassay,
      Microgenics). All immunoassays performed equivalently for cocaine, opiates, and
      phencyclidine. All immunoassays detected the same amphetamine/methamphetamine
      positive specimens, but all also detected numerous specimens containing cross
      reacting sympathomimetic amines. CEDIA detected 100%, Emit II 93%, and RIA 82% of
      the barbiturate-positive specimens. Emit II and CEDIA detected 86-88% of the
      specimens found by RIA to be marijuana positive. A subset of specimens was
      additionally screened by OnLine (Roche) and TDx (Abbott) for amphetamines,
      cocaine, and marijuana. OnLine and TDx also detected all of the amphetamine
      positive specimens and numerous specimens containing cross-reacting
      sympathomimetic amines. All immunoassays performed equivalently for cocaine, and
      the four nonisotopic tests detected 86-89% of the marijuana positives found by
      RIA. Interfering sympathomimetic amine drug compounds can be eliminated by using
      an oxidizing agent, thus decreasing the number of unconfirmable amphetamine
      presumptive positives. The CEDIAs for all of the major drugs of abuse are
      reliable and effective for large-volume urine screening programs.

PMID- 7813089
TI  - Continuous-flow assay with immobilized enzymes for determining of inorganic
      phosphate in serum.
AB  - An automated method for the determination of inorganic phosphate based on flow
      injection analysis and on the use of immobilized enzymes is reported. The method
      features a linear range between 0.1 and 20 mumol/L with a CV < 2.1% and 3.4% for
      the within-run and between-run studies, respectively, and a sampling throughput
      of 40 h-1. The sensitivity of the method makes a 1:250 dilution of the serum
      samples feasible, thus making undetectable the interferences from analytes
      commonly present in serum. The method shows an excellent correlation with
      conventional automated analyzers based on the same enzymatic reaction (Hitachi, r
      = 0.988) but with the catalyst in solution, and with the Kodak Ektachem method (r
      = 0.974) based on the use of dry reagents and formation of the phosphomolybdo
      heteropolyacid.

PMID- 7813090
TI  - Status of quantitative EEG (QEEG) in clinical practice, 1994.
AB  - Clinical quantitative EEG (qEEG) is a complex specialty that may include not only
      standard EEG but also digital ("paperless") EEG, topographic mapping, spectral
      analysis, spectral coherence, long latency and event related potentials (EP),
      significance probability mapping (SPM), dipole source localization methodology
      (DLM), and discriminant function analysis. There are three basic clinical uses:
      non-specific detection of organicity/encephalopathy, specific categorization of
      disease or clinical condition, and epileptic source localization. Extreme
      variations exist in the competency of laboratories practicing clinical qEEG;
      universally agreed upon standards of practice have not been established but there
      are a number of efforts to do so. As expected, the clinical value of qEEG to
      patients varies similarly. Criticisms of qEEG have now been answered: Color
      displays need not be deceptive. Statistical "capitalization upon chance" can be
      easily avoided. By training and with newer analytic procedures, artifacts can be
      recognized and often removed. Data based upon spectral analysis and EP can
      reliably classify clinical conditions thereby demonstrating a greater sensitivity
      to EEG/EP data than possible by conventional visual inspection. QEEG is clearly
      of clinical value when performed in concert with standard EEG and analyzed by
      clinicians with demonstrated competency in standard EEG followed by specialized
      training and demonstrated competency in qEEG. QEEG is not a simple substitute for
      conventional EEG and cannot be seen as a substitute for clinical competence.
      Although continuing to develop, qEEG technology has matured sufficiently and is
      now well established. Concerns regarding its clinical use have primarily resulted
      from its misapplication and misinterpretation stemming, largely, from inadequate
      personnel training and expertise.

PMID- 7813091
TI  - The use of the EEG to predict outcome in premature infants with positive sharp
      waves.
AB  - The goal of this study was to investigate the factors that could predict
      prognosis in 51 premature infants with positive sharp waves on their EEGs
      (gestational age 23-36 wks) with 114 tracings. Follow-up clinical examinations
      were conducted, up to 10 yrs later. Death occurred in 18%, from a non-CNS cause,
      either sepsis or a congenital cardiac or pulmonary defect. A severe outcome was
      seen in 8% and was related to maternal i.v. drug abuse (IVDA) and the presence of
      many positive sharp waves. A moderate outcome, noted in 29%, was associated with
      a Grade III-IV intracerebral hemorrhage (ICH) or periventricular leukomalacia
      (PVL) and maternal IVDA. A mild outcome seen in 20% was related to infrequent
      positive sharp waves, vaginal delivery and an improving EEG over time, while a
      normal outcome (26%) was also related to infrequent discharges, a normalized EEG
      over time, a normal sonogram and the absence of clinical seizures. The addition
      of negative sharp waves to the positive ones and the addition of central to
      temporal positive sharp waves were associated less often with a normal outcome.
      The general conclusion of this study was that various aspects of positive sharp
      waves in premature infants, in addition to other factors, can be used to predict
      outcome in these neonates.

PMID- 7813092
TI  - Event-related potentials to an "oddball" auditory paradigm in children with
      learning disabilities with or without attention deficit hyperactivity disorder.
AB  - Event Related Potentials (ERP) were recorded during a two-tone discrimination
      task in 18 children with Learning Disabilities (LD) and 36 children with Learning
      Disabilities and Attention Deficit Hyperactivity Disorder (LD-ADHD). Twenty-seven
      normal children served as a control group. P3 wave amplitude was significantly
      smaller in the LD and LD-ADHD groups compared with normal children. There was no
      difference between the LD and LD-ADHD groups. It is suggested that the smaller P3
      amplitude in children with LD-ADHD syndromes reflects cognitive and processing
      difficulties, which frequently coexist with ADHD in these children and is not
      specifically related to an attention deficit.

PMID- 7813093
TI  - Lennox-Gastaut syndrome in the elderly?
AB  - The Lennox-Gastaut syndrome (LGS) is an electro-clinical syndrome of early
      childhood that consists of mental retardation, intractable generalized epilepsy
      with multiple seizure types, and typical EEG findings. We report a 64-year-old
      woman who was referred for presurgical evaluation with a diagnosis of intractable
      temporal lobe epilepsy since the age of 14 years, consisting of staring and
      unresponsiveness, sudden falls, and generalized convulsions. The average seizure
      frequency was 1-4 per month. Mental status and neurological examination were
      normal. There was no known etiology and magnetic resonance imaging (MRI) of the
      brain was normal. Interictal EEG showed findings characteristic of LGS:
      generalized slow spike-wave complexes, multifocal sharp waves, generalized
      polyspikes and paroxysmal fast activity during sleep. Despite the absence of
      mental retardation and the presence of normal alpha rhythm, the patient fulfills
      most diagnostic criteria for LGS, with unusually late onset and extremely delayed
      diagnosis. This case illustrates the controversial nosologic boundaries of the
      syndrome. Prolonged EEG video monitoring may be of value even in the elderly. The
      LGS and other varieties of secondary generalized epilepsy should be considered in
      the syndromic diagnosis of epilepsy in the elderly.

PMID- 7813094
TI  - Clinical, electrophysiologic and neuroimaging findings in Wernicke's syndrome.
AB  - Wernicke's encephalopathy is a disease that when not diagnosed in time, can lead
      to severe CNS damage and death. It is characterized by specific clinical and
      radiologic findings; however, there are few reports dealing with the usefulness
      of neurophysiologic studies in this syndrome. We present a patient with
      Wernicke's encephalopathy, diagnosed postmortem on autopsy, in whom the
      neurophysiologic studies showed abnormalities in all the different pathways
      tested. This suggests that EEG and evoked potentials may be useful tools in the
      diagnostic workup of this entity. We propose performing these tests when this
      syndrome is being considered.

PMID- 7813095
TI  - Sleep apnea and periodic leg movements in epilepsy.
AB  - Sleepiness is a common complaint in the epilepsy clinic, and sleep disturbances
      are frequently reported by seizure patients. Polysomnography was performed in 6
      patients with complex partial seizures, with and without secondary
      generalization, who had not yet started anticonvulsant treatment or whose
      medication had been discontinued. Five patients sleep through the night, but 1
      slept only 3 hours. Two patients had reduced sleep efficiency and slow wave sleep
      was reduced or absent in 4 patients. No REM sleep disturbances occurred. Two
      patients had almost no periodic leg movements of sleep (PLMS), 2 had few or no
      arousals and PLMS indices of 5 or less, and 2 had markedly elevated PLMS and
      arousal indices. No apneas or significant hypopneas were recorded, but snoring
      indices were elevated in 2 patients. These findings suggest that sleep apnea is
      infrequent in unmedicated seizure patients. Some patients may have exaggerated
      PLMS with arousals, possibly related to epileptiform discharge and perhaps
      exacerbated by medications, but apparently not due to nocturnal seizures.

PMID- 7813096
TI  - Post-anoxic theta and alpha pattern coma.
AB  - Theta pattern coma is a rare EEG finding, described in the course of post-anoxic
      or post-traumatic coma and interpreted as a "malignant" variant of alpha pattern
      coma. A case of isolated theta pattern coma, followed by alpha pattern coma is
      reported. Short temporal succession of such patterns would seem to confirm the
      hypothesis of a close relationship between them. Possible physiological
      mechanisms involved in the generation of the patterns are discussed.

PMID- 7813097
TI  - Burst-suppression pattern with unusual clinical correlates.
AB  - A 44-year-old man suffered a severe anoxic encephalopathy with rapid fatal
      outcome. His EEG prior to expiration showed a burst-suppression pattern (BSP)
      with occurrence of two previously unreported clinical features: spontaneous
      chewing movements during the burst and tonic posturing during the suppression
      phase. In coma the appearance of BSP in the EEG commonly implies a severe
      anoxic/metabolic insult to the brain with a grave prognosis. The pattern is
      considered to be interictal, except in cases presenting with myoclonic status
      epilepticus. Subtle intermittent movements of the eye, mouth and cardiovascular
      rhythm are uncommon and it is unclear whether these are epileptic events or not.
      This case indicates that the suppression phase can also have associated clinical
      signs.

PMID- 7813098
TI  - Periodic lateralized epileptiform discharges in EEG during recovery from
      hyponatremia: a case report.
AB  - PLEDs were observed in a case of undifferentiated schizophrenia, transiently
      during the course of recovery from hyponatremia, and diffuse EEG slowing remained
      even after the serum sodium had returned to normal range. It was considered that
      PLEDs had occurred transiently in relation to hemispheric ischemic disturbance
      induced by hyponatremia. The characteristics of PLEDs associated with
      hyponatremia will need to be studied further in more patients with hyponatremia.

PMID- 7813099
TI  - In vitro analysis of metabolic predisposition to drug hypersensitivity reactions.
AB  - Idiosyncratic hypersensitivity reactions may account for up to 25% of all adverse
      reactions, and pose a constant problem to physicians because of their
      unpredictable nature, potentially fatal outcome and resemblance to other disease
      processes. Current understanding of how drug allergy arises is based largely on
      the hapten hypothesis: since most drugs are not chemically reactive per se, they
      must be activated metabolically to reactive species which may become immunogenic
      through interactions with cellular macromolecules. The role of drug metabolism is
      thus pivotal to the hapten hypothesis both in activation of the parent compound
      and detoxification of the reactive species. Although conjugation reactions may
      occasionally produce potential immunogens (for example, the generation of
      acylglucuronides from non-steroidal anti-inflammatory drugs such as diclofenac),
      bioactivation is catalysed most frequently by cytochrome P450 (P450) enzymes. The
      multifactorial nature of hypersensitivity reactions, particularly the role of
      often unidentified, reactive drug metabolites in antigen generation, has hampered
      the routine diagnosis of these disorders by classical immunological methods
      designed to detect circulating antibodies or sensitized T cells. Similarly,
      species differences in drug metabolism and immune system regulation have largely
      precluded the establishment of appropriate animal models with which to examine
      the immunopathological mechanisms of these toxicities. However, the combined use
      of in vitro toxicity assays incorporating human tissues and in vivo phenotyping
      (or, ultimately, in vitro genotyping) methods for drug detoxification pathways
      may provide the metabolic basis for hypersensitivity reactions to several drugs.
      This brief review highlights recent efforts to unravel the bases for
      hypersensitivity reactions to these therapeutic agents (which include
      anticonvulsants and sulphonamides) using drug metabolism and immunochemical
      approaches. In particular, examples are provided which illustrate breakthroughs
      in the identification of the chemical nature of the reactive metabolites which
      become bound to cellular macromolecules, the enzyme systems responsible for their
      generation and (possibly) detoxification, and the target proteins implicated in
      the subsequent immune response.

PMID- 7813100
TI  - A prospective controlled crossover trial of a new heat-treated intravenous
      immunoglobulin.
AB  - Twenty-one patients with primary immunoglobulin deficiency were enrolled in a
      crossover study to test the efficacy and safety of Alphaglobin in comparison with
      the licensed preparations Sandoglobulin and Gamimune. There was no statistical
      difference in these parameters between Alphaglobin and Sandoglobulin/Gamimune.
      The level of total serum IgG and specific IgG to pneumococcal polysaccharides was
      similar in individual patients when they were receiving Alphaglobin or one of the
      other products. Transient increases in serum alanine transferase occurred in five
      patients on Sandoglobulin/Gamimune and two patients on Alphaglobin. Some patients
      showed a rise in total serum IgM afterwards, indicating a response to infection.
      However, serum hepatitis C virus (HCV) RNA was not found during the alanine
      transferase (ALT) rises, and IgM antibody to hepatitis A virus (HAV) was negative
      afterwards. We conclude that Alphaglobin is a safe, well tolerated and clinically
      efficacious treatment for patients with primary antibody deficiency.

PMID- 7813101
TI  - IL-8 release from cultured peripheral blood monocytes of patients with
      glomerulonephritis.
AB  - IL-8 is a chemotactic cytokine with proinflammatory and growth-promoting
      activities. The release of IL-8 was measured in supernatants of cultured
      peripheral blood monocytes (PBM) that were obtained from patients with
      glomerulonephritis (GN) and healthy controls. Spontaneous and lipopolysaccharide
      (LPS)-induced IL-8 release was significantly higher in PBM isolated from patients
      with IgA nephropathy (IgAN) and membranous nephropathy (MN) compared with normal
      controls. These results raise the question of whether IL-8 contributes to the
      ongoing pathogenesis of GN. We cannot relate IL-8 release to clinical and
      laboratory parameters in IgAN and MN patients. Thus, disease progression in vivo
      may not be accompanied by increased or sustained IL-8 release.

PMID- 7813102
TI  - Low activity of the classical complement pathway predicts short survival of
      patients with chronic lymphocytic leukaemia.
AB  - The activities of the classical (CP) and alternative (AP) complement pathways as
      well as the levels of some complement components and circulating immune complexes
      were measured in 43 patients with chronic lymphocytic leukaemia (CLL) between
      1980 and 1984. Depressed CP activities were frequently found in these patients.
      Clinical course of the disease in the patients was followed until 1992, and
      compared with the initial complement values. During the follow-up period 36
      patients died, death of 33 patients being related to the underlying disease. A
      strong positive correlation (P < 0.01) was found between the length of survival
      of the patients and the initial CP values. Patients were divided into two groups:
      group A, short-term survivors, i.e patients who died in CLL-related complications
      within 3 years after the complement measurements; and group B, long-term
      survivors who died > or = 4 years after the complement measurements due to any
      cause, or were alive at the end of the follow-up period. Average CP values in
      Group B were almost twice those in group A (P = 0.002), and a similar but less
      pronounced difference was found in C3 levels (P = 0.055). These differences were
      even more marked (P = 0.0006 and P = 0.0015, respectively) when only patients in
      Rai stage 2 and 3 were considered. Low classical pathway activities predicted
      short survival time: according to the logrank test, patients in Rai stage 2-3
      with low (< mean - 2s.d. of the normal values), and normal CP levels survived for
      2.0 +/- 1.1, and 4.6 +/- 3.0 years, respectively. All the nine and 11/13 patients
      with low CP and C4 levels, respectively, died within 3 years after the complement
      measurements were made. These findings indicate that complement measurements
      performed in CLL patients have a clinical value.

PMID- 7813103
TI  - A rare mediastinal tumour presenting with systemic effects due to IL-6 and tumour
      necrosis factor (TNF) production.
AB  - Patients presenting with prolonged systemic illnesses with no specific clinical
      or serological defining features may be diagnosed as having atypical systemic
      vasculitides, but often turn out to have occult malignancies. Cytokines have been
      implicated in causing many of the systemic effects in such cases. In this study
      we describe a patient presenting after 2 years of a severe systemic illness with
      a marked acute phase response, due to an occult mediastinal angiomatoid malignant
      fibrous histiocytoma. Tumour resection was curative. We evaluated in detail the
      local and systemic production of cytokines induced by this tumour. Blood samples
      were taken pre- and post-operatively for cytokine studies. In vitro production of
      IL-2, IL-2R, IL-1 beta, IL-6 and TNF-alpha by cultured monocytes from the
      patient, as well as plasma cytokine levels, were measured by ELISA. Tumour
      cytokine production was also evaluated immunocytochemically, and by in situ
      hybridization with specific cDNA probes. Plasma IL-2R and IL-6, and IL-6 and TNF
      alpha production by peripheral blood monocytes were markedly elevated before
      tumour resection, normalizing post-operatively. Most tumour cells and
      infiltrating lymphocytes stained with antibodies to IL-6, IL-6R and TNF-alpha,
      and expressed HLA class II. IL-6 and TNF-alpha mRNA production in the tumour was
      confirmed by in situ hybridization studies. We have described the first case of
      an occult angiomatoid malignant fibrous histiocytoma in the mediastinum. Studies
      of cytokine expression suggested that chronic TNF, IL-6, and IL-2 production by
      leucocytes and tumour cells in this patient was responsible for the severe
      systemic illness with which she presented.

PMID- 7813104
TI  - Effect of IL-4 and interferon-gamma (IFN-gamma) on IL-3- and IL-5-induced
      eosinophil differentiation from human cord blood mononuclear cells.
AB  - IL-4 and IFN-gamma positively and negatively regulate allergic inflammation. To
      determine the regulatory mechanisms of eosinopoiesis by cytokines, we examined
      the effect of recombinant IL-4 and IFN-gamma and of anti-IL-4 and anti-IFN-gamma
      antibodies on IL-3- and IL-5-induced eosinophil differentiation from human
      umbilical cord blood mononuclear cells. rhIL-4 (10-300 U/ml) inhibited IL-3- and
      IL-5-induced eosinophil differentiation from cord blood mononuclear cells on day
      28 of culture by 62-81% in a concentration-dependent manner. rhIFN-gamma (5-500
      U/ml) also inhibited IL-3- and IL-5-induced eosinophil differentiation by 80-99%
      in a concentration-dependent manner. The inhibitory effect of rhIL-4 and rhIFN
      gamma was observed only when rhIL-4 or rhIFN-gamma were present in the culture
      from day 0 to day 14, but not from day 15 to day 28. Addition of anti-IL-4
      antibody to the culture enhanced IL-3- and IL-5-induced eosinophil
      differentiation on day 28 of culture by 30%, whereas anti-IL-2 MoAb and anti-IFN
      gamma MoAb had no significant effect. These results indicate that IL-4 and IFN
      gamma have inhibitory effects on IL-3- and IL-5-induced eosinophil
      differentiation from its progenitor cells.

PMID- 7813105
TI  - IL-1 is expressed in human adrenal gland in vivo. Possible role in a local immune
      adrenal axis.
AB  - IL-1 is an important mediator in the dialogue between the immune system and the
      hypothalamo-pituitary-adrenal axis. A direct influence of IL-1 upon adrenal
      steroidogenesis has been demonstrated in experimental animals. We therefore
      designed a study to see if IL-1 is expressed within the normal human adrenal
      gland. The combination of in situ hybridization and specific immunostaining to IL
      1 beta was eminently suited to demonstrate both mRNA and protein production. The
      specific immunostaining of the different cells combined with in situ
      hybridization (IL-1) allowed us to identify the exact cellular source of IL-1. IL
      1 mRNA occurred in the zona reticularis in 17 alpha-hydroxylase positive steroid
      cells surrounding the adrenomedullary cells. Some CD68+ macrophages in this zona
      showed a positive signal. A weak signal was seen to IL-1 mRNA in few chromaffin
      cells, while IL-1-like immunoreactivity was more frequent. We conclude that in
      the normal situation in man IL-1 is mainly expressed in specialized cortical
      cells. The occurrence of the major glucocorticoid inducing factor in the normal
      human adrenal gland itself provides evidence for an autocrine or paracrine
      reaction under physiological conditions.

PMID- 7813106
TI  - Soluble CD4 antigen reactivity in intravenous immunoglobulin preparations: is it
      specific?
AB  - Soluble CD4 antigen (sCD4) was measured in seven commercially available
      intravenous immunoglobulin preparations (IVIg) by means of a double determinant
      immunoassay (DDIA), whereby two MoAbs recognizing two distinct and spatially
      distant epitopes on CD4 were used to capture and detect the antigen,
      respectively. Preincubation of six out of seven IVIg, which were found to be
      apparently positive for sCD4, with mouse- and bovine-derived serum or purified
      immunoglobulins completely neutralized DDIA reactivity for sCD4. The inhibition
      was specific since it was not or only partially observed when IVIg were mixed
      with whole serum or purified IgG from rabbit. Extensive absorption of six IVIg on
      insolubilized mouse IgG (mIgG) resulted in a complete loss of reactivity. Eluted
      human anti-mouse antibodies (HAMA) from any of the IVIg displayed a dose
      dependent binding in a DDIA, though its extent varied from one preparation to
      another. Western blot analysis showed that HAMA from all IVIg contained no
      component with a molecular weight identical with or close to that of recombinant
      CD4. Purified mIgG markedly influenced the sCD4 reactivity of two IVIg
      (Sandoglobulin and Globuman I.V.) when sCD4 was measured with a purchased 'CD4
      specific Test Kit', thus suggesting that HAMA can exceed the absorbing capacity
      of the sample diluent. Taken as a whole, these data indicate that sCD4-based DDIA
      signal is mostly, if not completely, generated by the presence of human
      immunoglobulin with anti-mouse immunoglobulin reactivity, thus casting doubts on
      the actual occurrence of sCD4 in IVIg.

PMID- 7813107
TI  - Failure of IgG production due to a defect in the opening of the chromatin
      structure of I gamma 1 region in a patient with IgG and IgA deficiency.
AB  - Patients with common variable immunodeficiency (CVID) display reduced levels of
      two or all three of the major immunoglobulin isotypes, and the deficiency is
      characterized by failure of B cells to differentiate into plasma cells in many
      cases. A patient (14 years old, female) showed normal serum IgM levels and low
      serum IgG and IgA levels, including low levels of all IgG subclasses. Northern
      blot analysis suggested that the patient's B cells may be defective at the
      immunoglobulin heavy chain isotype switch. The germ-line C gamma 1 transcript was
      amplified from cDNA of healthy controls by the addition of recombinant IL-2 (rIL
      2) to pokeweed mitogen-stimulated peripheral mononuclear cells or Staphylococcus
      aureus Cowan I (SAC)-stimulated IgM-producing lymphoblastoid cell lines (LCL)
      transformed by Epstein-Barr virus, while it was not amplified from cDNA of the
      patient. In the I gamma 1 region of LCL cultured with SAC plus rIL-2, the inner
      cytosine in the 5' C-C-G-G 3' sequence nearest the 3' site of the I gamma 1
      region, at least, was not completely unmethylated in the patient. Moreover, the
      DNase I hypersensitive site was not induced in the patient's LCL by SAC plus rIL
      2. These results indicate that the defects of the immunoglobulin heavy chain
      isotype switch in the patient's B cells are due to failure in the synthesis of
      germ-line C gamma transcripts, and this may be caused by defects in opening of
      the chromatin structures of specific switch regions.

PMID- 7813108
TI  - Anti-p57: a novel association with neonatal lupus.
AB  - IgG antibodies to a 57-kD protein (p57) present in various human and bovine
      extracts were detected by immunoblotting in the serum of the mother of a baby
      with congenital heart block, but not in the corresponding cord blood, suggesting
      specific antibody consumption in the baby. Since this indicates a possible
      functional role for these antibodies, the antigen target was characterized and
      the association of the antibodies to heart block was further studied. A human
      K562 lambda gt11 cDNA library was screened and two clones were identified whose
      products reacted with the prototype serum. Antibody affinity-purified by use of
      the cloned gene products reacted on immunoblot with the 57-kD band. Partial
      sequences of both inserts were identical, but differed from DNA encoding the
      Ro(SSA) and La(SSB) antigens. Antibodies to the p57 were detected in 10% of
      systemic lupus erythematosus (SLE) sera, almost exclusively in association with
      anti-Ro(SSA). Furthermore, they were present in 38% (8/21) mothers of babies with
      neonatal lupus expressing either cardiac or cutaneous manifestations. Antibodies
      to this 57-kD protein may be an additional risk factor for neonatal lupus in anti
      Ro-positive women. Moreover, disappearance of antibody from cord blood suggests
      that they may have a role in disease manifestations.

PMID- 7813109
TI  - Bactericidal/permeability-increasing protein (BPI) is an important antigen for
      anti-neutrophil cytoplasmic autoantibodies (ANCA) in vasculitis.
AB  - Indirect immunofluorescence (IIF) techniques have shown that ANCA are useful
      serological markers for some small vessel vasculitides, and ELISA assays, using
      purified molecules as solid-phase ligand, have helped to identify proteinase 3
      (PR3) and myeloperoxidase (MPO) as two of the major ANCA antigens. There remain a
      substantial number of serum samples, which are positive by IIF, yet recognize
      neither PR3 nor MPO (double-negative samples). We found, by Western blot analysis
      of soluble neutrophil granule proteins, that certain of these double-negative
      samples recognized a 55-kD doublet of which the first eight residues shared N
      terminal amino acid sequence homology with BPI, a potent antibiotic towards Gram
      negative bacteria. We developed a simple, quick and robust two-step
      immunobiochemical method to purify BPI. This was then employed to detect anti-BPI
      autoantibodies by ELISA and Western blot analysis. We tested 100 double-negative
      samples and 400 consecutive new samples sent for routine ANCA testing in the anti
      BPI ELISA. We found that 45 of the 100 double-negative and 44 of the 400 new
      routine samples recognized BPI. By Western blot analysis 20/20 positive anti-BPI
      samples blotted the 55-kD protein. Inhibition assays confirmed the specificity of
      binding. Review of the 89 anti-BPI-positive patients showed a male dominance (M:F
      ratio 55:34), a mean age of 60.4 years and clinical diagnoses ranging from organ
      limited vasculitis to widespread systemic vasculitis.

PMID- 7813110
TI  - Analysis of gamma delta V region usage in normal and diseased human intestinal
      biopsies and peripheral blood by polymerase chain reaction (PCR) and flow
      cytometry.
AB  - The intestinal population of gamma delta T cell receptor (TCR)-bearing cells was
      characterized with regard to V delta and V gamma subtype expression. For this
      purpose, we utilized V gene-specific PCR of mRNA prepared from intestinal
      biopsies. Predominant expression of the V delta 1 subtype was demonstrated in the
      small intestine of patients with coeliac disease and in the inflamed colon of
      patients with inflammatory bowel diseases (IBD: ulcerative colitis and Crohn's
      disease) as well as in colon biopsies taken from macroscopically normal areas of
      colon. Although intestinal gamma delta T cells preferentially expressed V delta
      1, other V delta transcripts could be detected, of which V delta 2 and V delta 5
      were commonly expressed. Analysis of biopsies from mesenteric lymph nodes
      demonstrated a V delta repertoire similar to the mucosa. In peripheral blood on
      the other hand, high expression of both V delta 2 and V delta 1 was found. The
      predominant expression of V delta 1 transcripts in the intestinal mucosa of IBD
      patients correlated well with protein cell surface expression as analysed by flow
      cytometry using V delta 1- and V delta 2-specific antibodies. Selective expansion
      of gamma delta T cells could not be demonstrated within the inflamed mucosa as
      shown by mRNA analysis and flow cytometry. Instead, IBD patients demonstrated a
      decreased proportion of TCR gamma delta-carrying T cells in the inflamed mucosa
      compared with macroscopically normal area of colon. On the other hand, a
      significantly increased percentage of T cells bearing the gamma delta TCR was
      found in peripheral blood of patients with Crohn's disease compared with healthy
      individuals, indicating that local mucosal inflammation may influence the
      circulating gamma delta T cell population.

PMID- 7813111
TI  - A role for IL-4 in immunologically mediated enteropathy.
AB  - A number of clinical enteropathies are associated with a local cell-mediated
      immune (CMI) response, and experimental evidence indicates that cytokines are
      responsible for the intestinal pathology. We show here that depletion of IL-4
      using MoAb or a soluble form of the IL-4 receptor (IL-4R) prevents the jejunal
      manifestations of a proliferative form of murine graft-versus-host reaction
      (GVHR) characterized by crypt hyperplasia and recruitment of intraepithelial
      lymphocytes (IEL). Depletion of IL-4 did not prevent the appearance of villus
      atrophy in a destructive model of GVHR, and had no effect on any indices of
      systemic immunity. These results indicate that IL-4 may play a selective role in
      mediating proliferative aspects of intestinal immunopathology, and suggest that
      this cytokine may provide a useful target for immunotherapy.

PMID- 7813112
TI  - Technical report: results of immunological tests on faecal extracts are likely to
      be extremely misleading.
AB  - Clinical investigation of gut immunity is difficult because of the need to study
      intestinal tissues or secretions directly. Others have reported that
      immunoglobulins, antibodies and cytokines can be detected in saline extracts of
      faeces. We have assessed the validity of this approach by measuring
      immunoglobulins, albumin, alpha 1-antitrypsin and isotype-specific antibodies in
      matched samples of faeces and whole gut lavage fluid. Results were compared as
      estimated output per day, and by using haemoglobin as a common reference
      substance. Samples were obtained from 10 patients with active inflammatory bowel
      disease and 10 with other benign GI diseases. For immunoglobulins, albumin and
      antibodies, the amount detected in faeces varied from < 0.01% to 35.5% (based on
      estimated daily output) and < 0.01% to 18.5% (based on haemoglobin) of the amount
      known to be produced in the gut from results of assays on whole gut lavage fluid
      (WGLF); there were significantly higher rates of recovery in faecal specimens
      from patients with active gut inflammation than from other patients. Detection
      rates and titres of specific antibody in faeces were even lower than those for
      immunoreactive IgA. These data indicate that immunological tests on saline
      extracts of faeces do not represent the true status of the gut humoral immune
      system, and such studies should be strongly discouraged.

PMID- 7813114
TI  - Lysis of human macrophages by cytolytic CD4+ T cells fails to affect survival of
      intracellular Mycobacterium bovis-bacille Calmette-Guerin (BCG).
AB  - Human CD4+, mycobacteria-specific, cytolytic T cell clones were used to lyse BCG
      infected macrophages, and the effect on the subsequent growth and viability of
      the organisms was examined. The survival of released bacteria following cell
      lysis was assessed by both 3H-uridine labelling and colony-forming unit (CFU)
      estimation. The results indicate that even when effective antigen-specific or
      lectin-mediated cytolysis of the infected macrophages was achieved, there was no
      evidence for a direct mycobactericidal effect on the intracellular bacteria. This
      remained the case even if the period of co-culture of T cells and macrophages was
      extended up to 48 h. Pretreatment of the macrophages with interferon-gamma (IFN
      gamma) was not able to act together with T cell-mediated lysis to produce
      inhibition of mycobacterial growth.

PMID- 7813113
TI  - Interferon-gamma (IFN-gamma) production by human T lymphocytes upon Legionella
      pneumophila stimulation in vitro.
AB  - In vitro immune responses to Legionella pneumophila were investigated. When human
      peripheral blood lymphocytes (PBL) from healthy volunteers were stimulated with
      formalin-killed L. pneumophila for 7 days in vitro, strong proliferative
      responses were observed. The responding cells were shown to be a CD4 T cell
      subset. It was also found that the CD4 T cells secreted significant amounts of
      IFN-gamma into the PBL culture supernatant. The production of IFN-gamma and IL-4
      by PBL was measured semiquantitatively by reverse transcriptase-assisted
      polymerase chain reaction (RT-PCR) methods. Formalin-killed or live L.
      pneumophila-stimulated PBL expressed the mRNA for IFN-gamma but not the mRNA for
      IL-4. The results suggest that the whole bacterium, as opposed to the
      supernatant, predominantly stimulates Th1 type helper T cells. The cloned T cells
      specific for L. pneumophila expressed the mRNA for IFN-gamma but not for IL-4. In
      contrast to formalin-killed or live L. pneumophila stimulation, when PBL were
      stimulated with the bacterial culture supernatant, the proliferating T cells
      produced the mRNA for IL-4 as well as for IFN-gamma. A significant correlation
      between the proliferative response to formalin-killed L. pneumophila and IFN
      gamma release in culture was observed (r = 0.6932, P < 0.001) in PBL from 30
      healthy volunteers. From these in vitro studies, it is suggested that the whole
      L. pneumophila bacterium and their soluble antigens stimulate T cells in a manner
      which results in a different pattern of cytokine production.

PMID- 7813115
TI  - Lack of cytotoxic activity against Mycobacterium leprae 65-kD heat shock protein
      (hsp) in multibacillary leprosy patients.
AB  - Cytotoxic T cells play an important role in host defence mechanisms, as well as
      in the immunopathology of leprosy. In this study, we evaluated whether
      Mycobacterium leprae hsp18, hsp65 and Myco. tuberculosis hsp71 could induce
      cytotoxic T cell activity against autologous macrophages pulsed with these hsp.
      Paucibacillary (PB) patients and normal controls generated more effector cells
      than multibacillary (MB) patients with all three hsp tested. There was no cross
      reactivity between any of the hsp tested. Mycobacterium leprae hsp65 induced
      cytotoxic responses only in those MB patients undergoing an erythema nodosum
      leprosum (ENL) episode. Although hsp65 and hsp18 induced similar proliferation in
      MB patients, a high proportion of these patients did not generate cytotoxic
      effector cells in response to hsp65. Hence, those T cells reacting to hsp65 may
      play an important role in the control of Myco. leprae infection.

PMID- 7813117
TI  - Primary immunodeficiency diseases. Report of a WHO Scientific Group.

PMID- 7813116
TI  - In vitro and in vivo T cell responses in mice during bronchopulmonary infection
      with mucoid Pseudomonas aeruginosa.
AB  - In vitro and in vivo T cell responses were determined during the course of
      bronchopulmonary infection with mucoid Pseudomonas aeruginosa. T cell responses
      were compared in two inbred mouse strains, namely BALB/c mice, which are
      resistant to the establishment of chronic bronchopulmonary Ps. aeruginosa
      infection, and C57Bl/6 mice, which have high numbers of bacteria in the lungs
      through 14 days post-infection. Unseparated lung cells and lung T cells from
      BALB/c mice exhibited significantly higher in vitro proliferative responses to
      both heat-killed Ps. aeruginosa and concanavalin A (Con A) than cells from
      C57Bl/6 mice through 20 days post-intratracheal infection with 10(4) colony
      forming units (CFU) Ps. aeruginosa. Proliferation of unseparated lung cells but
      not lung T cells from BALB/c mice infected 6 days previously with 10(5) CFU Ps.
      aeruginosa was suppressed in response to Con A; these cells were unresponsive to
      specific antigen. Suppression of lymphocyte proliferation in the lungs of C57Bl/6
      mice infected with 10(4) CFU Ps. aeruginosa and in BALB/c mice infected with
      10(5) CFU was found to be mediated by adherent lung cells via the production of
      nitric oxide and prostaglandins. Determination of in vivo T cell-mediated
      responses in infected mice demonstrated that resistant BALB/c mice had high DTH
      and low Pseudomonas-specific antibody responses, while C57Bl/6 mice had low DTH
      and high antibody levels, in particular, IgG2b and IgM.

PMID- 7813118
TI  - Potassium channel openers and other regulators of KATP channels.
AB  - 1. Interest in ATP-sensitive K (KATP) channels first arose when it was shown that
      hypoglycaemic sulphonylureas, such as glibenclamide, closed these channels in
      pancreatic beta-cells to cause insulin release. The demonstration that certain
      smooth muscle relaxants (K channel openers) may exert their actions through
      opening a similar channel in vascular smooth muscle fueled further investigation
      of these channels and their physiological role in a variety of tissue types,
      including various types of smooth muscle, cardiac and skeletal muscle and neural
      and endocrine organ function. 2. The K channel openers have a variety of
      potential therapeutic applications, including disorders of smooth muscle
      hyperreactivity, such as hypertension, and a great deal of research has focused
      on this field. More recently, attention has turned to the cardiac actions of
      these compounds and this area is discussed in detail. One of the current problems
      is the lack of selectivity of KATP channel regulators. However, there have been a
      number of recent encouraging reports suggesting that, under certain
      pathophysiological conditions, the action of the K channel openers may be
      enhanced, conferring upon them some degree of selectivity. 3. A number of
      endogenous regulators of these channels have been identified, particularly in the
      category of endogenous openers of these channels. At present though, the
      physiological role of these channels and the endogenous regulators identified, is
      unclear. 4. It is evident that, although advances have been made, much work is
      still required to increase our understanding and ultimately to allow selective
      pharmacological manipulation of these channels to become a therapeutic reality.

PMID- 7813119
TI  - Possible mechanisms involved in the natriuretic response to atrial natriuretic
      factor (ANF) and proANF 31-67 in the rat.
AB  - 1. The present study was conducted to compare the mechanisms involved in the
      natriuretic response to atrial natriuretic factor (ANF) and proANF 31-67. The
      peptides were infused intravenously into anaesthetized rats at 10 pmol/min for 40
      min. 2. Only ANF produced a significant decrease in arterial pressure; the
      maximum decrease was 11 mmHg (P < 0.05). 3. Both peptides produced significant
      increases in sodium excretion (P < 0.05) but only ANF increased the cyclic GMP
      (cGMP) excretion rate (P < 0.01) and neither peptide had a significant effect on
      plasma renin activity or glomerular filtration rate (GFR). ProANF 31-67 did not
      increase the plasma levels of ANF. 4. These results demonstrate that both ANF and
      proANF 31-67 have natriuretic effects via a tubular mechanism and suggest that
      the natriuretic effects of ANF are mediated by cGMP while the excretion, changes
      in GFR or a reduction in renin secretion.

PMID- 7813120
TI  - Effect of increased myocardial cyclic GMP induced by cyclic GMP-phosphodiesterase
      inhibition on oxygen consumption and supply of rabbit hearts.
AB  - 1. We tested the hypothesis that increasing myocardial cyclic GMP levels would
      reduce myocardial O2 consumption and areas of low O2 supply/consumption balance,
      using zaprinast, a selective cyclic GMP-phosphodiesterase inhibitor. 2. The study
      was conducted in three groups (vehicle, 10(-3) and 3 x 10(-3) mol/L zaprinast) of
      anaesthetized open-chest New Zealand white rabbits (n = 24). Coronary blood flow
      (radioactive microspheres), arterial and venous O2 saturation
      (microspectrophotometry), O2 consumption, cyclic GMP content (competitive
      binding) and cyclic GMP-phosphodiesterase activity (conversion of 3H-cyclic GMP
      to 3H-GMP) were determined. 3. Agents were applied to a patch on the myocardial
      surface and did not cause significant haemodynamic changes, except for
      bradycardia in the vehicle and low dose group. 4. The total myocardial cyclic GMP
      phosphodiesterase activity was 148 +/- 14 while the zaprinast (10 mumol/L)
      inhibitable activity averaged 63 +/- 8 pmol/mg protein per min. Cyclic GMP
      content was increased with increasing doses of zaprinast (vehicle, 4.308 +/-
      0.349 pmol/g; low dose zaprinast, 4.803 +/- 0.279 and high dose zaprinast, 7.938
      +/- 1.304 pmol/g). 5. Coronary blood flow was not different after treatment (198
      +/- 11, 209 +/- 10 and 153 +/- 9 mL/min per 100 g for the vehicle, low and high
      dose zaprinast, respectively). 6. Under control conditions, 48% of the small
      veins had O2 saturations below 50%. With zaprinast, this value was reduced to 19%
      for the low and 24% for the high dose. 7. Average venous O2 saturation increased
      with zaprinast (49 +/- 2%, 61 +/- 3% and 59 +/- 1%).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7813121
TI  - The effect of cocaine and desipramine on neuronal uptake of [3H]-noradrenaline
      and sensitivity to noradrenaline of rat mesenteric resistance arteries.
AB  - 1. The effects of cocaine and desipramine (DMI) on neuronal uptake (uptake1) of
      [3H]-noradrenaline (NA) and isometric tension development to exogenous NA were
      assessed in mesenteric resistance arteries of Wistar rats. 2. Both drugs
      concentration-dependently inhibited [3H]-NA uptake1, DMI being more potent than
      cocaine. The maximum inhibition produced by each drug was the same as that
      produced by denervation with 6-hydroxydopamine. In denervated vessels there was
      no effect of cocaine on [3H]-NA uptake1. 3. Cocaine, in the same concentration
      range which caused inhibition of uptake1, increased the sensitivity to NA, while
      DMI, in a concentration range which inhibited uptake1, did not increase the
      sensitivity to NA and at high concentrations reduced the sensitivity and maximal
      response to NA. Since DMI affected responses to NA but not responses to
      vasopressin and potassium its effect is probably related to blockade of alpha 1
      adrenoceptors. 4. We conclude that the effect of cocaine on the sensitivity to NA
      reflects inhibition of uptake1 in rat resistance arteries, while DMI cannot be
      used to assess the functional effect of uptake1 in this preparation.

PMID- 7813122
TI  - Dextrose-, adenosine- and magnesium-induced protective actions during anoxia and
      reperfusion in canine Purkinje tissue.
AB  - 1. The effects of dextrose, magnesium (Mg) and adenosine on membrane potential
      and force of contraction were studied in driven and overdriven canine cardiac
      Purkinje tissue. 2. Dextrose (50 mmol/L) and adenosine (4-6 mmol/L) both showed
      protective action (the latter to a lesser extent) against simulated anoxia and
      reperfusion-induced arrhythmias, increased force of contraction transiently on
      reperfusion, and the former sustained the increase in force to a lower level as
      long as it was in the superfusing solution. 3. Dextrose (50 mmol/L) and Mg (5
      mmol/L) restored overdrive-induced hyperpolarization during simulated anoxia.
      Adenosine was largely ineffective. 4. It was concluded that dextrose and
      adenosine (to a lesser extent) protect against arrhythmias by replenishing the
      critical intracellular pool of ATP which controls membrane transport of
      electrolytes such as K and Ca. Restoration of Na-K ATPase activity alone (as in
      the case of high Mg concentrations) is not sufficient to prevent arrhythmias.

PMID- 7813123
TI  - Prorenin and active renin concentrations in ovarian follicular fluid increase
      after the LH peak in superovulated heifers.
AB  - 1. The aim was to analyse the in vivo variations with time of prorenin and active
      renin and their relationship to steroid hormones in ovarian follicular fluid
      during follicular growth in heifers. 2. Thirty one beef heifers were assigned to
      two groups after oestrous synchronization: an unstimulated and a follicle
      stimulating hormone (FSH)-treated (superovulated) group. Within each group,
      animals were slaughtered at different times of the follicular phase of the
      oestrous cycle. Ovarian follicular fluids were aspirated and analysed for the
      concentrations of active renin, prorenin, oestradiol-17 beta (E2) and
      progesterone (P4). 3. Prorenin and active renin concentrations in follicular
      fluid remained constant until the luteinizing hormone (LH) peak, after which time
      they increased four- and two-fold, respectively, in superovulated heifers. 4. In
      follicular fluid, prorenin and active renin correlated negatively with oestradiol
      and E2/P4 ratio but positively with progesterone during follicular growth in
      superovulated heifers. Prorenin also correlated negatively with oestradiol and
      E2/P4 ratio in unstimulated heifers. 5. The increase of renin concentrations in
      ovarian follicles after the LH peak and the correlations to steroid hormones
      suggest an important role of the ovarian renin-angiotensin system in bovine
      follicular growth and maturation.

PMID- 7813124
TI  - Characterization of binding sites for [3H]-idazoxan, [3H]-P-aminoclonidine and
      [3H]-rauwolscine in the kidney of the dog.
AB  - 1. We characterized the binding of [3H]-rauwolscine, [3H]-p-aminoclonidine and
      [3H]-idazoxan in a dog kidney membrane preparation. Our aim was to determine the
      pharmacological nature of the alpha 2-adrenoceptor- and imidazoline-preferring
      binding sites in this organ. 2. [3H]-Rauwolscine bound to an apparent single site
      with an affinity (KD) of 2.2 nmol/L and a maximum density (Bmax) of 58.5 fmol/mg
      protein, when 10 mumol/L idazoxan defined non-specific binding. However
      displacement studies demonstrated that a number of compounds, including prazosin,
      inhibited [3H]-rauwolscine binding in a complex manner consistent with
      displacement from two distinct binding sites. The majority (69%) of the [3H]
      rauwolscine binding sites had a relatively low affinity for prazosin (KI = 398
      nmol/L), while the remainder had a relatively high affinity for prazosin (KI =
      7.9 nmol/L). 3. [3H]-p-Aminoclonidine bound to an apparent single site (KD = 5.2
      nmol/L; Bmax = 72.4 fmol/mg protein), when 10 mumol/L phentolamine defined non
      specific binding. When 1 mumol/L of the potent and selective alpha 2-adrenoceptor
      antagonist 2-methoxyidazoxan was included in the incubate, no specific binding
      was detected. We therefore conclude that under the conditions of this experiment
      [3H]-p-aminoclonidine binds only to alpha 2-adrenoceptors in the dog kidney. 4.
      [3H]-Idazoxan bound to two sites, with a higher (KD = 0.95 nmol/L; Bmax = 43.9
      fmol/mg protein) and lower (KD = 9.1 nmol/L; Bmax = 93.8 fmol/mg protein)
      affinity, respectively, when 1 mmol/L phentolamine defined non-specific binding.
      When 10 mumol/L GTP gamma S was included in the incubate, the low affinity site
      was unaffected but the maximum binding at the higher affinity site was reduced by
      79%. 2-Methoxyidazoxan displaced [3H]-idazoxan in a monophasic manner and with
      low potency (IC50 = 11.5 mumol/L). Yohimbine, efaroxan, clonidine, rilmenidine,
      guanabenz and idazoxan itself displaced [3H]-idazoxan in a complex manner; the
      slope of the displacement curves being less than unity. 5. We conclude that the
      dog kidney contains a heterogeneous population of alpha 2-adrenoceptors that can
      be labelled either with [3H]-rauwolscine or [3H]-p-aminoclonidine. The dog kidney
      also contains a heterogeneous population of non-adrenoceptor imidazoline
      preferring binding sites of the I2-subtype, that can be labelled with [3H]
      idazoxan. The binding site for which [3H]-idazoxan has the highest affinity
      appears to be coupled to a guanine nucleotide binding regulatory protein.

PMID- 7813125
TI  - Low cholesterol and impaired cardiac function following heart transplantation.
AB  - 1. During follow-up of 59 cardiac transplant recipients over 2 or more years, a
      small group of subjects was observed who displayed an unpredictable, relatively
      marked, reduction in plasma cholesterol. 2. A significant proportion of these
      subjects were subsequently observed as having experienced a marked decline in
      left ventricular function at the time of routine radionuclide ventriculography.
      3. While the mechanism for this fall in cholesterol is unclear, the observation
      of such an unexpected reduction in total cholesterol, late after heart
      transplantation should be considered significant and prompt further investigation
      including an assessment of allograft function.

PMID- 7813126
TI  - Policy and politics--a necessity for inclusion in nursing curricula: our nursing
      practice depends on it!

PMID- 7813127
TI  - Use of the neural network for hypothesis generation in fetal surveillance.

PMID- 7813128
TI  - Quantification of fetal heart rate variation using a probability distribution
      matrix.
AB  - Analysis of FHR variability attempts to be able to distinguish which FHR changes
      are physiological and which are pathological. From the results of such studies,
      it is hoped that clinicians will be provided with the means to identify
      accurately which fetuses are healthy, which are at risk and which are actually in
      distress at any gestational age. The probability distribution matrix presented
      has the outstanding advantage of enabling one to condense any amount of FHR data
      into one uniform description for analysis en bloc. Not even one FHR is
      sacrificed; each one contributes to the FHR vs. DFHR distribution pattern. Where
      the probability distribution matrix is made from many FHR samples taken from
      healthy fetuses under natural day-to-day maternal circumferences, as we have
      done, this matrix can be considered as a physiologically unbiased reference. The
      subtraction matrix is characterized by the difference in FHR vs. DFHR
      distribution patterns between two probability distribution matrices compared,
      representing the equal residue of net absolute value. The larger the difference
      in FHR vs. DFHR distribution between two probability distribution matrices, the
      larger these kinds of residue values, and if two probability distribution
      matrices are identical, all the elements in the subtraction matrix indicate the
      residue values of zero. Our probability distribution matrix approach confirms the
      results of previously reported studies which utilized other analytical
      strategies. Therefore, we can evaluate quantitatively age-related FHR changes
      used as variables, such as the subtraction matrix and difference rate. By varying
      intervals between paired FHRs (e.g. selecting the original FHR--skip--select the
      following FHR--skip 2 FHR--select the next FHR, etc.), the probability
      distribution matrix could be adopted as a general tool for analysis of sequential
      changes in large numbers of FHR for further studies.

PMID- 7813129
TI  - Intrapartum prediction of fetal status and assessment of labour progress.

PMID- 7813130
TI  - Development, evaluation and validation of an intelligent system for the
      management of labour.
AB  - Over the past 4 years our group has developed a prototype intelligent system
      which applies captured expert knowledge to support clinical decision-making
      during labour. This chapter presents a review of the system and the progress made
      to date. The system classifies the same features from the CTG as experienced
      clinicians using numerical algorithms and a small neural network. This hybrid
      approach has been shown to obtain a comparable performance with experts. The CTG
      information, together with the patient information and labour events, are
      collectively passed to an expert system for processing. The expert system
      interprets this combined data using a database of over 400 rules which are used
      to recommend action. Importantly, as the knowledge is rule-based, it allows the
      system to explain the reasoning which led it to recommend a certain action. In
      this way, the clinician is not expected to blindly follow the system's
      recommendations but can reach an informed judgement in the same way they might by
      discussing the case with an experienced informed colleague. After two internal
      evaluations had found the system obtained a performance comparable with local
      experts, an extensive external validation was undertaken. This study involved 17
      experts from 16 leading centres within the UK. Each expert and the system
      reviewed 50 cases twice, at least one month apart which contained those CTGs
      considered most difficult to interpret selected from a database of 2400 high-risk
      labours. This study found that the majority of experts agreed well and were
      consistent in their management of the cases. The system obtained a performance
      that was indistinguishable from the experts, except it was more consistent, even
      when used by an engineer with little knowledge of labour management. This study
      demonstrates the potential for intelligent systems to transform the
      cardiotocograph from a difficult-to-use, ineffective recorder of fetal heart
      rate, to an interactive and effective decision support tool capable of raising
      the skills of staff.

PMID- 7813131
TI  - Prediction of future outcome using Bayesian logic.

PMID- 7813132
TI  - Decision analysis in clinical genetics.

PMID- 7813133
TI  - Power spectral analysis of fetal heart rate.
AB  - This chapter examines the role of power spectral analysis (PSA) in elucidation of
      the physiological control mechanisms of fetal heart rate and as a potential
      indicator of fetal well-being. The importance of fetal heart rate variability
      (FHRV) as an indicator of fetal oxygenation is discussed, and the limitations in
      the current methods of measurement of FHRV are highlighted. Evidence is presented
      for the paramount influence of the autonomic nervous system in the control of
      heart rate variability. The basic proposition underlying spectral analysis is
      that the two autonomic branches influence heart rate in a frequency-dependent
      way, and their differential effects can be determined by PSA which breaks down
      the heart rate trace into its component frequencies. The application of PSA to
      heart rate variability data is an established tool in cardiology, and the
      published literature related to its use in the adult, neonate and fetus is
      reviewed. The power spectrum is sensitive to the activity state of the fetus,
      particularly fetal breathing movements, which have a variable effect on short-
      and long-term FHRV. There are a variety of mathematical approaches to the
      construction of power spectra, and a particular method of data acquisition and
      analysis is presented together with some theoretical background. Recent
      experimental evidence indicates a role for PSA as an indicator of fetal activity
      state, and the effect of hypoxia on the spectrum of the fetus in labour is
      discussed. There are some problems with the technique of PSA, particularly in
      regard to accepted definitions and methods of analysis. It is a powerful non
      invasive tool in the elucidation of fetal cardiac control, but its value in the
      detection of the compromised fetus has yet to be tested in a clinical trial.

PMID- 7813134
TI  - Cardiac systolic time intervals and other parameters of myocardial contractility
      as indices of fetal acid-base status.
AB  - Electronic fetal heart rate monitoring has become the standard method for the
      assessment of fetal status during labour. Unfortunately, the hoped-for benefit
      from implementation of this technique has not been realized. The non-specific
      nature of FHR changes has led to undesirable side-effects, especially an increase
      in inappropriate operative interventions. Thus, there is an obvious need for
      methods which will improve upon the accuracy of FHR monitoring. There is
      substantial evidence for a tight coupling of fetal acid-base balance and
      myocardial contractility. This relationship has been established in experimental
      animal studies where fetuses were gradually rendered hypoxic and acidaemic while
      myocardial contractility was assessed by dP/dtmax and end-systolic elastance
      (Ees). Furthermore, the correlation between pH and indices of contractility
      extends over the entire range of clinical importance rather than being a terminal
      event. Systolic time intervals have long been recognized as good indicators of
      myocardial contractility. Recent advances in technology, have made their
      measurement in the human fetus by non-invasive means feasible. Substantial
      evidence has been accumulated, from both animal and human studies, to indicate
      that fetal STIs and especially the PEP and PEP/VET ratio are good predictors of
      fetal acid-base status. Other indices of fetal myocardial function, such as
      Doppler-derived aortic acceleration time and peak acceleration, have also emerged
      as having a potential benefit in monitoring the fetus before and during labour.
      Fetal STIs and other indices of myocardial contractility may be valuable adjuncts
      to FHR monitoring. During labour, STIs may prove to be of value both to elucidate
      equivocal FHR patterns and to detect fetal hypoxaemia and acidaemia. For this to
      occur, the sensitivity and specificity have to be determined by large-scale
      prospective clinical trials comparing STIs to current monitoring methods.

PMID- 7813135
TI  - Effective utilization of home-video recordings for the evaluation of paroxysmal
      events in pediatrics.
AB  - In young children, differentiating seizures from nonepileptic "spells" by history
      alone can be difficult, even for the specialist. Nonepileptic spells may be
      psychogenic (rare in the young child) or physiologic in origin. Physiologic
      spells misidentified as epileptic may be treated with antiepileptic medication
      where none is needed. Recording spells on video provides a potentially valuable
      supplement to the clinical history in arriving at a correct diagnosis. In
      practice, however, most home-video recordings prove difficult to interpret.
      Simple instructions to parents on the manner in which spells should be recorded
      will greatly increase the usefulness of home-video recordings. A systemic
      analysis of precipitating factors and the evolution and resolution of the spell
      will very often exclude seizures. The widespread availability of home-video
      recordings provides the pediatrician with an opportunity to visually examine a
      child's spells, often avoiding unnecessary investigations and referrals and
      allowing the physician to more confidently offer reassurance to the parents.

PMID- 7813136
TI  - Subependymal (grade 1) intracranial hemorrhage in neonates on extracorporeal
      membrane oxygenation. Frequency and patterns of evolution.
AB  - Intracranial hemorrhage (ICH) is a potential contraindication to extracorporeal
      membrane oxygenation (ECMO) therapy in neonates, since systemic anticoagulation
      required during ECMO may increase the incidence and progression of ICH. To
      determine the frequency and the pattern of evolution of subependymal hemorrhage
      (SEH) (grade 1 ICH) in neonates on ECMO, the daily head ultrasound (HUS)
      examinations obtained as part of a prospective neurologic evaluation protocol in
      212 ECMO patients were reviewed. Forty-three patients (20%) had a total of 65
      SEHs. Twenty-two infants had bilateral SEH. Twenty-eight infants developed 38
      SEHs during ECMO bypass after pre-ECMO HUS showed no evidence of ICH. An
      additional 18 neonates had a total of 22 SEHs demonstrated on pre-ECMO HUS. No
      pre-ECMO HUS was performed in four infants having a total of five SEHs first
      identified during ECMO bypass. Of the 65 SEHs, 59 (91%) remained stable or
      resolved during ECMO, while six (9%) evolved during ECMO--three to grade 2, one
      to grade 3, and two to grade 4 ICH. Our data suggest that SEH should not be
      considered a contraindication to ECMO bypass and very infrequently will progress
      significantly during ECMO.

PMID- 7813137
TI  - Growth patterns of hyperlipidemic children enrolled in a preventive
      cardiovascular health clinic.
AB  - The objective of this study was to assess growth patterns of hyperlipidemic
      children enrolled in a preventive cardiovascular health clinic. A retrospective
      chart review of hyperlipidemic children enrolled in the Mayo Clinic
      Cardiovascular Health Clinic for the Young was performed. All participants were
      counseled to eat an American Heart Association Step-One Diet and exercise
      regularly. Weight and height were measured every 3 months. Growth was assessed
      using attained heights and weights and body-mass index Z scores compared to
      standard distributions for North American children. Sixty-three patients (33
      males and 30 females) were enrolled in the study. Mean age at clinic entrance was
      7.8 +/- 3.5 years (range: 2 to 16 years). We conclude that participation in a
      preventive health clinic is generally safe for hyperlipidemic children. However,
      medical management of hyperlipidemic children must include meticulous
      surveillance to detect the infrequent occurrence of excessive weight loss or
      weight stabilization resulting from inappropriate response to dietary counseling.

PMID- 7813138
TI  - Progression of tympanometry and acoustic reflectometry. Findings in children with
      acute otitis media.
AB  - The presence of middle ear effusion (MEE) following acute otitis media (AOM) has
      been assessed by impedance tympanometry and acoustic reflectometry but has not
      been assessed serially from the time of presentation for AOM in the same group of
      patients. This descriptive study examined serial measurements by tympanometry and
      reflectometry in children with clinical AOM at the time of diagnosis, 3 to 5 days
      later, and at final follow-up 12 to 15 days after diagnosis. The study entry
      criteria were conservative in order to represent obvious cases of AOM and
      included 90 patients representing 107 ears. The objective was to describe the
      evolution of instrumental findings and to attempt to identify unique patient
      subpopulations with differing prognoses. We found that combined use of initial
      tympanometry and reflectometry, while yielding intriguing results, does not allow
      for identification of subpopulations with good or poor progression for MEE
      clearance at 2-week follow-up. It is our conclusion that initial tympanometry and
      reflectometry add to the cost of AOM diagnosis without clear benefit for the
      individual patient.

PMID- 7813139
TI  - Knowledge of gonorrhea in adolescent females with a history of STD.
AB  - The purpose of this study is to examine how a previous infection with gonorrhea
      or another sexually transmitted disease (STD) will impact on patients' knowledge
      of gonorrhea. Adolescent girls were recruited from a primary-care adolescent
      clinic. Those with a history of an STD were overrecruited. Participants were
      given a standardized questionnaire regarding several symptoms and sequelae of
      STD. The results of this study revealed that girls (N = 248, mean age = 16.9
      years) with a personal history of gonorrhea had more correct responses than those
      with no history of an STD, but they were not statistically different from those
      with a nongonococcal STD. No group had a mean correct score greater than 6.66 out
      of 13. Nearly two out of three participants reported that an individual had to
      always have one of four symptoms (discharge, pain on urination, rash, or sores)
      when there is a gonococcal infection. Overall, adolescents have an inaccurate
      foundation of knowledge regarding symptoms and sequelae of gonorrhea. Although
      those with a previous history of gonorrhea had higher mean scores than those with
      no history of an STD, they still identified the correct responses only half the
      time. Additionally, adolescents with a history of gonorrhea or another STD were
      no more likely to have identified the possibility of asymptomatic infection,
      despite several having only a history of asymptomatic infection.

PMID- 7813140
TI  - Scleredema revisited. A poststreptococcal complication.
AB  - Scleredema is a rare connective disease which must be differentiated from
      scleroderma in childhood. Scleredema is characterized by thickening of the dermis
      of the neck, head, and upper trunk. We report a case of scleredema in an 8-year
      old boy with coincident streptococcal colonization. The patient report
      demonstrates many of the common features of scleredema, including an associated
      streptococcal infection, a relatively benign presentation of illness, and the
      characteristic mucopolysaccharide intradermal staining on skin biopsy. The
      literature on scleredema is reviewed, focusing on the disease course,
      differential diagnosis, and an overview of the proposed three subgroups of
      scleredema. The association of scleredema to a prior streptococcal infection is
      explored, and a proposed autoimmune pathophysiology of the disease, as it relates
      to streptococcal infection, is presented.

PMID- 7813141
TI  - Multifocal M. intracellulare osteomyelitis in an immunocompetent child.
AB  - We report the successful treatment of disseminated Mycobacterium intracellulare
      osteomyelitis, without evidence of other visceral involvement, in a previously
      healthy, HIV-negative, 2-year-old female using a 23-month regimen of
      antimicrobial agents that included 18 months of oral therapy with azithromycin,
      rifabutin, trimethoprim-sulfamethoxazole (TMP/SMX), and ethambutol.

PMID- 7813142
TI  - Preventing behavior problems in asthma and allergies.

PMID- 7813143
TI  - Intensive care. Impact on resident education.

PMID- 7813144
TI  - Severe failure to thrive and liver dysfunction as the main manifestations of a
      new variant of Niemann-Pick disease.

PMID- 7813145
TI  - Misdiagnosis of perianal manifestations of Crohn's disease. Two cases and a
      review of the literature.

PMID- 7813146
TI  - Phenytoin-induced movement disorder. Unilateral presentation in a child and
      response to diphenhydramine.

PMID- 7813147
TI  - Using dead space flush: a critical step in blood sampling from an umbilical
      artery catheter.

PMID- 7813149
TI  - Etiopathogenesis of craniofacial anomalies.
AB  - This article reviews the current information available on the etiopathogenesis of
      craniofacial anomalies with a particular emphasis on craniosynostosis. The
      incidence of various types of craniosynostosis is presented, along with an
      overview of the causes of malformations and deformations. The basic development
      of cranial sutures and fusion is explored as a background for the exploration of
      advances in genetic and molecular biology. This information lays the foundation
      for our understanding of craniofacial deformities and their response to surgical
      treatment described in the the other articles of this issue.

PMID- 7813150
TI  - Perspectives on craniofacial growth.
AB  - This article underscores the importance of the growth process in the production
      of normal and abnormal craniofacial morphology. Although much has been learned
      over the past century, we still have only a limited appreciation of the 3D
      changes that occur in the skull during postnatal growth. We have also stressed
      that the current cooperation between reconstructive surgeons and radiologists is
      producing a substantive amount of data that could be used to further our
      understanding of the postnatal growth process. At The Johns Hopkins University we
      are putting our efforts toward the collection and organization of a large data
      base of craniofacial images that will allow us to study questions about the role
      growth plays in mediating the results of reconstructive surgery. Our ultimate
      goal is to provide information about the future appearance of craniofacial
      patients based on empirically derived growth patterns. In a recent article
      Dufresne and Richtsmeier proposed that the results of surgical correction may be
      predicted based on the etiology of the craniofacial condition, and not
      necessarily the degree or character of the dysmorphology. The authors hypothesize
      that a categorization or classification of craniofacial dysmorphology can be
      proposed, based on the response of individuals to surgery, and that such a
      classification reflects real differences in etiology. Hence, a poor response to
      surgery reflects a condition that includes a growth disorder, whereas cases that
      respond positively to reconstructive surgery are those in which the growth
      process is not part of the dysmorphology. In the latter cases, a dysmorphic face
      is surgically transformed into an acceptable morphology, and normative growth
      vectors maintain or improve postoperative facial appearance. Thus, Dufresne and
      Richtsmeier13 suggest that this divergence in the response to surgery among
      patients relates directly to the role of the growth process in various types of
      dysmorphologies. Using our tools and the data base we are forming, we envision a
      markedly different preoperative consultation for future craniofacial patients.
      When a patient is evaluated, images from the data base with a similar diagnosis
      will be used to calculate a growth pattern for the proper age interval. The
      patient's scan is then "grown" according to the appropriate growth pattern. The
      parents and patient can evaluate this new image and see what their child's skull
      will look like 2, 3, or 4 years from the present, both with and without
      reconstructive surgery. In addition, our tools will statistically compare the
      simulated (or "grown") skull to samples of craniofacial images of normal and
      affected children of an age/sex/ethnic population that matches the patient. This
      testing will determine whether growth results in the patient becoming more
      normal, or more different from normal, with time.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7813151
TI  - Craniofacial computer-assisted surgical planning and simulation.
AB  - Computer-assisted planning and simulation of craniofacial surgery has progressed
      from development, through validation, and into clinical use. CT scans are
      transferred from the radiology department to a graphics workstation in the
      surgeon's office or laboratory, where data postprocessing and visualization for
      anatomic evaluation and surgical simulation are performed. Quantitative and
      qualitative comparative analyses between the plan/simulation and the actual
      postoperative result provide the feedback that validates or refutes the
      preoperative assessment and simulated intervention. The optimum surgical solution
      can be chosen from many possibilities. Interactive computer-assisted surgical
      simulation is also useful for morbidity-free training of inexperienced surgeons.

PMID- 7813148
TI  - A hypothesis for early intervention in SIDS.

PMID- 7813152
TI  - Experimental studies addressing rigid fixation in craniofacial surgery.
AB  - This article has reviewed several experimental studies that address certain
      aspects of the use of rigid fixation in clinical craniofacial surgery. The effect
      of rigid fixation on growth was studied in an infant Rhesus monkey model. It
      showed that osteotomy and fixation resulted in subtle changes in skull shape and
      that the severity of the deformity was related to the complexity of the fixation
      employed. Deformities were seen with wire fixation alone, however. A study using
      a rabbit model showed that the revascularization and resorption of onlay bone
      grafts immobilized with a microscrew occurred primarily in the cancellous portion
      of the graft. This led Chen et al to speculate that the volume of cranial bone
      grafts persists better than with iliac crest grafts, because they contain
      relatively less cancellous bone and more cortical bone, which is slower to
      revascularize and resorb. Fiala et al studied the artifacts seen in CT and MR
      scans associated with plate and screw fixation devices. They showed that,
      compared with stainless steel and vitallium, titanium resulted in less
      "starburst" and "black hole" artifact in CT and MR images, respectively. Amarante
      et al compared butyl-2-cyanoacrylate adhesive fixation with fixation by plates
      and screws of osteotomized bone segments in a minipig model. They found it to be
      as effective as plates and screws for bone fixation in this model. In the future,
      this material, together with resorbable plates and screws, may provide a means of
      fixation of the craniofacial skeleton and can be anticipated to receive further
      experimental and clinical study.

PMID- 7813153
TI  - Bone grafts and bone induction substitutes.
AB  - The use of bone grafts is the basis of all craniofacial surgery. Bone grafts are
      used to stabilize the open segments, expand the patient's structural boundaries,
      and fill defects created by trauma or congenital malformations. Bone grafts are
      harvested from local or distant sites as indicated. Biomaterial implants are used
      as bone substitutes when it is not possible to use bone grafts.

PMID- 7813154
TI  - Frontal plagiocephaly. Diagnosis and treatment.
AB  - Plagiocephaly is the term loosely applied to frontal or posterior cranial
      asymmetry. Deformational plagiocephaly is the most common form. Synostotic
      frontal plagiocephaly is usually sporadic, but can be syndromic or familial.
      These two major categories of plagiocephaly are distinguishable by physical
      findings. Deformational plagiocephaly tends to self-correct during infancy; this
      process can be ameliorated by conservative measures. Synostotic frontal
      plagiocephaly requires surgical correction during infancy.

PMID- 7813155
TI  - Surgical correction of metopic suture synostosis.
AB  - Premature fusion of the metopic suture is an uncommon form of craniosynostosis,
      historically reported with an incidence of less than 10% among the various forms
      of craniosynostoses. Despite its infrequency, it is the most obvious deformity
      associated with premature fusion of a single suture with its prominent frontal
      keel, narrow forehead, and close-set eyes. This article discusses the timing,
      long-term results, and recent advances of surgical techniques.

PMID- 7813156
TI  - Sagittal synostosis.
AB  - Sagittal synostosis comprises a spectrum of deformities caused by premature
      fusion of the sagittal suture. The treatment of sagittal synostosis is dependent
      on the age of the patient and the characteristics of the presenting deformity.
      Immediate correction of the scaphocephalic deformity is the goal of operative
      treatment. The operative procedures proposed involve whole-vault cranial
      reshaping, active shortening of the anteroposterior axis, and widening of the
      mediolateral dimension of the skull leading to a more normal, "rounded" skull
      shape.

PMID- 7813157
TI  - Lambdoid synostosis.
AB  - Recent increases in presentation of occipital deformities have presented the
      craniofacial team with new challenges in diagnosis and treatment. As presented in
      this article, they appear to have a functional abnormality of the suture that
      results in a localized growth deformity. The growth inhibition in severe cases
      can result in changes in the local bone and brain, along with the entire skull
      and cranial base. Histologic analysis supports the theory that this is true
      lambdoid synostosis. Surgical correction is indicated in moderate to severe
      cases, and the authors have presented their technique and new data on outcomes.

PMID- 7813158
TI  - The craniofacial dysostosis syndromes. Current reconstructive strategies.
AB  - The author's preferred approach to the management of the craniofacial dysostosis
      syndromes is to stage the reconstruction to coincide with the facial growth
      patterns, visceral (brain and eye) function, and psychosocial development.
      Recognition for the need for a staged reconstruction approach serves to clarify
      the objectives of each phase of treatment for the surgeon, the craniofacial team,
      and the family unit. By continuing to define the rationale for the timing and
      extent of surgical intervention, then objectively evaluating both functional and
      morphologic outcomes, surgeons will further improve the long-term function and
      facial aesthetics for patients born with these complex syndromes.

PMID- 7813159
TI  - Orbital hypertelorism.
AB  - Excessive distance between the orbits is only one manifestation of a complex
      deformity that affects several skeletal and soft-tissue structures. This article
      discusses the classification, preoperative planning, and surgical procedures used
      in the reconstruction of orbital hypertelorism.

PMID- 7813160
TI  - Treacher Collins syndrome (mandibulofacial dysostosis).
AB  - Treacher Collins syndrome is a complex congenital malformation. The most
      important manifestations of this syndrome are hypoplastic or absent malar bone,
      centrofacial over-projection, eyelid coloboma, and micrognathia. This article
      presents an approach to re-establish the right centrofacial proportions through
      "flattening osteotomies" of the maxilla, malar bone reconstruction, and other
      maxillo-mandibular osteotomies.

PMID- 7813161
TI  - The role of distraction osteogenesis in the reconstruction of the mandible in
      unilateral craniofacial microsomia.
AB  - Laboratory and clinical studies have shown that mandibular distraction is an
      effective and powerful reconstructive surgical technique. It is safely performed
      without the need for blood transfusion or bone graft. Because of concomitant
      expansion of the functional matrix (the associated skin, subcutaneous fat, and
      muscles of mastication), there is a multidimensional expansion of the lower jaw
      with minimal, if any, evidence of relapse. Moreover, the surgical reconstruction
      can be commenced by 2 years of age, and the vector of distraction can be
      controlled by preoperative design. Finally, the increase in resulting mandibular
      bone stock will provide more reconstructive options in the future for traditional
      orthognathic surgical techniques. The technique has been criticized, either for
      the cutaneous incision for the approach to the mandible or for the scar resulting
      from the path of the distracting screws. However, with careful placement of the
      device, the resulting scar can be placed in the lines of minimal tension with a
      resulting satisfactory scar. It has been assumed that the osteotomy results in
      interruption of the inferior alveolar nerve. However, questioning of the older
      patients has failed to detect any change in sensation of the lower lip. The
      status of the inferior alveolar nerve in the hypoplastic mandible has also never
      been studied. Insertion of the screws required an area of bone stock that is
      edentulous, and this finding can make application of the device difficult in some
      patients. The length of treatment has been criticized--approximately 3 months.
      However, this is offset by the ease of treatment, the degree of safety, and the
      reduction in hospital time without the need for blood transfusion or bone graft.
      The results to date indicate that the technique can be applied to the correction
      of the milder mandibular deficiencies.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7813162
TI  - Craniofacial tumors.
AB  - The management of craniofacial tumors is presented, beginning with a discussion
      of terminology and anatomy. The importance of imaging is stressed. The
      significance of the internal carotid artery and an investigation of cerebral
      artery supply also are given. The most significant advances in the treatment of
      these tumors have been the soft-tissue approaches, but methods of disassembling
      the bony face for the ultimate in exposure are also important. Free tissue
      transfer has been a great advance in reconstruction and prevention of infection
      and in giving some patients a second chance for further radiation. With the
      application of newer techniques of exposure and resection, together with
      vascularized reconstruction, the prognosis from these tumors has improved and the
      complications have been reduced.

PMID- 7813163
TI  - Aesthetic craniofacial surgery.
AB  - The concepts of craniofacial surgery developed by Paul Tessier have evolved
      through four different phases: reconstruction, restoration, remodeling, and
      rejuvenation. Subperiosteal undermining of the upper, mid, and lower face allowed
      surgeons not only to reposition the soft tissues at the level of the bony
      insertion but also to remodel the craniofacial skeleton by either reduction or
      augmentation. Subperiosteal undermining of the face can be applied to treat a
      series of aesthetic defects of congenital, traumatic, or degenerative conditions.

PMID- 7813164
TI  - [Endogenous anti-analgesic systems].
AB  - Nociception is of vital importance for the organism, while its inhibition by
      endogenous opioid systems is usually a sign of surrender. Therefore, it must be
      assumed that endogenous analgesic systems are balanced, and in fact, under normal
      conditions, overwhelmed, by teleologically far more important anti-analgesic
      systems. The two main anti-analgesic systems--i.e., the melanotropinergic and the
      cholecystokininergic--are here reviewed for their role, not only in nociception,
      but in a wide variety of vital functions (endocrine, gastrointestinal, ingestive,
      reproductive, cardiovascular, immune, etc.). Available data strongly suggest that
      these systems (particularly the melanotropinergic one) play a key role in the
      overall homeostasis of the body. Moreover, modulation of endogenous anti
      analgesic systems may disclose a new, unforeseen approach to the treatment of
      pain.

PMID- 7813165
TI  - [The nephrotic syndrome and pheochromocytoma. A report of a rare clinical case].
AB  - In clinical practice, the coincidence of nephrotic syndrome with pheochromocytoma
      is very rare. The case is described of a 23-year-old woman who in June 1988
      presented with recurrent hypertensive crises, severe asthenia, abundant sweats,
      orthostatic hypertension and massive proteinuria. Diagnostic tests performed
      (abdominal ultrasound and CT, urinalysis, renal function tests, plasma levels of
      metanephrine and normetanephrine, as well as urinary VMA determination) revealed
      the presence of a pheochromocytoma of the left adrenal gland combined with
      nephrotic syndrome. Surgical removal of the left adrenal led to immediate
      normalization of blood pressure and absence of urinary abnormalities. The authors
      therefore suggest either an immunological pathogenesis or one due to glomerular
      hyperfiltration.

PMID- 7813166
TI  - [The evaluation of in-hospital precoronary times. The experience of a department
      of emergency medicine].
AB  - The above study was aimed at evaluating the "in-hospital precoronary times" of
      patients with acute myocardial infarction presenting to the Emergency Department
      of Policlinico Umberto I, Rome. From April to August 1993, 58 cases of acute
      myocardial infarction were admitted. In six of these, over 24 hrs had elapsed
      before admission. In 24 of the remaining cases thrombolysis was indicated. Mean
      time before admission to the coronary unit was 5 hrs for 52 patients. Mean in
      hospital delay before starting thrombolysis was 40 +/- 20 minutes; mean delay
      before admission to the coronary unit was 3 h/45 min. In-hospital time before
      thrombolysis was one of the lowest in the literature and shows the efficient
      organization of the department. Delay until transfer to the coronary unit was
      long and is a sign of the paucity of these specialized beds. Therefore, the
      possibility to perform thrombolytic therapy immediately in the emergency
      department becomes even more essential.

PMID- 7813167
TI  - Clinical investigation on the hypolipidemic effect of simvastatin versus probucol
      in hemodialysis patients.
AB  - In chronic renal failure hypertriglyceridemia is a well-known complication that
      persists during hemodialysis treatment: it may be one of the major risk factor
      for cardiovascular death in these patients. We studied the effects of two lipid
      lowering drugs; simvastatin (20 mg/day for six months) and probucol (500 mg/day
      for six months), on lipid profile in 12 hemodialysis patients. Simvastatin
      therapy reduced plasma total cholesterol by 26% (p > 0.002), LDL-cholesterol by
      36% (p > 0.002) and triglycerides by 28% (p > 0.05): plasma HDL-cholesterol and
      apo-A were raised, but not significantly. Probucol therapy decreased plasma
      triglycerides by 38% (p > 0.05), total cholesterol by 15% and LDL-cholesterol by
      19%: plasma HDL-cholesterol and apo-A were decreased but not significantly. No
      side effects occurred with either drug. These data suggest that in hemodialysis
      patients both simvastatin and probucol profoundly affect the lipid profile, as
      well as the triglyceride levels.

PMID- 7813168
TI  - [The efficacy of nedocromil sodium in light or moderate allergic bronchial
      asthma].
AB  - Inhaled nedocromil sodium was administered 4 times a day for 8 weeks to 34
      patients (20 males and 14 females) with mild to moderate allergic asthma to grass
      pollen. The study was conducted during the pollen season and patients were
      allowed extra medication only with beta 2 adrenergic drugs. On a diary card
      patients had to report daily variation of peak expiratory flow rate, severity and
      number of asthma attacks, severity of cough and use of bronchodilators. At the
      end of the study we observed a statistically significant improvement of all the
      parameters considered. No side effects were reported. Nedocromil sodium is
      therefore a useful and safe drug for the treatment of mild and moderate allergic
      asthma.

PMID- 7813169
TI  - [Allergy in pregnancy].
AB  - During pregnancy, the ideal would be to abstain from the use of any drug, at
      least during the first three months. In fact, none of the drugs currently used
      for the therapy of allergies has been classified by the FDA and European
      Commission on the basis of controlled human and animal studies as completely
      negative from the point of view of untoward effects in pregnancy. The following
      are considered comparatively safe: disodium cromoglycate, diphenhydramine,
      chlorpheniramine, hydroxyzine, mebhydroline, brompheniramine, inhaled beta 2
      agonists, xanthine bronchodilators, pseudoephedrine, and topical nasal treatment
      with beclomethasone dipropionate in the last trimenon. On the contrary, specific
      immunotherapy is inadvisable. In the case of anaphylaxis, epinephrine and
      ephedrine are drugs of choice, while in asthma monitoring of PEFR is essential
      for appropriate management. For rhinitis, DSCG and beclomethasone diproprionate
      appear to he comparatively safe. For urticaria, hydroxyzine or possibly ephedrine
      should be preferred. In case of a history of untoward drug effects, oral
      antibiotics should be preferred (erythromycin or micamycin); for atopic
      dermatitis the preference is for topical treatment with hydrocortisone.

PMID- 7813170
TI  - [Magnetic resonance angiography in the study of cervical and endocranial vascular
      pathology].
AB  - The principles of MR angiography techniques for the detection of vascular anatomy
      are discussed in this review. We underlined the possibilities and limits of this
      technique with its advantages and disadvantages. We also discuss the applications
      of MR angiography in diagnosing of cerebrovascular or neoplastic diseases.
      Finally we stress the role of MR angiography in clinical practice, and its
      reliability, in comparison with digital angiography, conventional angiography,
      and spiral CT.

PMID- 7813171
TI  - [Magnetic resonance spectroscopy].
AB  - Although the usefulness and feasibility of MR spectroscopy in clinical practice
      has not been proven, this technique has shown to be useful for the understanding
      of pathogenetic mechanisms of several diseases. In this work we reviewed the most
      important fields of application of MR spectroscopy and discussed its diagnostic
      potential.

PMID- 7813172
TI  - [Diffusion and perfusion studies with magnetic resonance imaging in cerebral
      ischemia].
AB  - The results of diffusion-perfusion RM studies in cerebrovascular diseases are
      reviewed in this paper. We discussed the role of these techniques for the
      understanding of the pathogenesis of cerebral ischemia, in experimental studies
      as well as in humans and their future application in diagnostic clinical trials,
      for early detection and management.

PMID- 7813173
TI  - [An emblematic case: gastroesophageal reflux].

PMID- 7813174
TI  - Early plaque accumulation--a sign for caries risk in young children.
AB  - Four variables which are capable of measurements at the chairside were assessed
      for their ability to identify young children who would experience caries during
      the subsequent 1 1/2 yr period. The total of 92 children and their mothers
      participated the study. The age of the children at baseline was 19 months. The
      variables studied were: visible plaque on the labial surfaces of the maxillary
      incisors, the use of a nursing bottle, mother's caries prevalence and mother's
      salivary level of mutans streptococci. Visible plaque and the use of a nursing
      bottle were strongly associated with the caries development, while the other two
      variables had weak or no statistically significant associations. The best
      indicator of risk was visible plaque. Its sensitivity was 83%, specificity 92%,
      positive prognostic value 63% and negative prognostic value 97%. Overall, 91% of
      the children were correctly classified with this variable, while the
      corresponding percentage of the other variables ranged from 72 to 77. The results
      suggest that visible plaque on the labial surfaces of maxillary incisors of a
      young child is a sign of caries risk.

PMID- 7813175
TI  - Self-reported gingivitis and bleeding gums among adolescents in Helsinki.
AB  - The purpose of this descriptive cross-sectional community based investigation was
      to analyze the relationship between professionally measured and perceived
      gingival health in a sample of 1217 adolescents (age 14.0 +/- 0.7 yr). The
      responses to two questionnaire items relating to self-reporting of "gingivitis"
      ("inflammation of gums" in Finnish) and "bleeding from gums" are reported along
      with Community Periodontal Index of Treatment Needs (CPITN), percentage of
      bleeding sites (BOP%) and modified Papillary Bleeding Index (PBI) scores. It was
      found that current or past "gingivitis" was less often reported than "bleeding
      from gums" by this sample and that responses to both items exhibited low levels
      of agreement with the clinical measures. The results suggest that the self
      reporting of gingival health may be useful in monitoring the gingival health of
      populations but does not have sufficient validity for screening individuals for
      gingivitis as defined by dental professionals. Furthermore, it is suggested that
      the term "bleeding from gums" rather than "gingivitis" should be used during
      clinical or group oral health promotion.

PMID- 7813176
TI  - Dental caries experience and defects of dental enamel among 12-year-old children
      in north London, Edinburgh, Glasgow and Dublin.
AB  - A multi-center study of caries experience and defects of dental enamel was
      conducted among 12-yr-old children in north London, Edinburgh, Glasgow and
      Dublin. None of the cities had water fluoridation except Dublin, which was
      included in the national program introduced in the Republic of Ireland in 1964. A
      random sample of children was drawn from state schools in each location and
      identical methods of clinical examination were used throughout under the same
      standardized conditions. All examiners were trained and calibrated with a
      reference examiner and achieved high levels of inter- and intra-examiner
      consistency. Mean DMFT values for the 4 cities were 1.27 (London), 1.39
      (Edinburgh), 2.70 (Glasgow) and 1.48 (Dublin) (P < 0.001). Proportions of
      subjects free from caries in the same order were, 50, 47, 24 and 43% (P < 0.001),
      and child prevalence of diffuse opacities, 28, 29, 7 and 17% (P < 0.001),
      respectively. The relatively low caries levels recorded in London and Edinburgh
      (lower than Dublin) were considered to be related most probably to fluoride
      effects other than water fluoridation.

PMID- 7813177
TI  - Timing of eruption of permanent teeth: standard Finnish patient documents.
AB  - Current standards for the eruption of teeth are constructed mostly on the basis
      of cross-sectional data. The aim here was to analyze the suitability of the
      standard patient documents created for health center dental care purposes for the
      collection of longitudinal data on tooth emergence. Copies of the oral health
      records of the 911 children born in 1970 and 1971 and in 1980 and 1981 living in
      three rural communities in Finland were re-examined and analyzed using a
      specially compiled computer program. The means and standard deviations are in
      line with previous results. The sex difference in emergence timing ranged from
      0.1 to 1.0 years for the various teeth. The emergence of the teeth of the second
      phase of the mixed dentition was later in the children living in an endemic
      fluoride area, this difference being statistically greater for the boys than for
      the girls (95% Cl for differences between means was used to evaluate statistical
      significance). A secular trend in the eruption of permanent teeth was found
      between 1970 and 1980. Patient documents are shown to be suitable for the
      collection of longitudinal data on dental emergence.

PMID- 7813178
TI  - Nursing caries, linear hypoplasia, and nursing and weaning habits in Tanzanian
      infants.
AB  - A cross-sectional survey on the prevalence of rampant caries in infants and a
      case-control study were executed to determine the prevalence of rampant caries
      and its etiology. A total of 2192 infants aged between 1 and 4.0 yr from nine
      regions of Tanzania comprised the sample of the prevalence survey. The overall
      prevalence of rampant caries resembling nursing caries was 6.8%. The prevalence
      varied considerably between 1.5% and 12.8% in the different regions and was
      closely associated with the varying prevalence of linear hypoplasia but not with
      fluoride content in drinking water. The relative risk of developing rampant
      caries in the presence of linear hypoplasia was 14.5. The case-control study
      comprised 116 cases, infants with rampant caries and 243 controls, without the
      disorder. Risk factors such as breast feeding frequency and duration during day
      and night, bottle feeding and weaning habits were assessed through a structured
      interview with the mother. Bottlefeeding was performed in only a minority of the
      infants for a short period (1.1 months) and in a low exposure frequency (0.4
      daily) and was not associated with rampant caries. The frequency of sugar moments
      in the supplementary diet was on average 1.5 times per day and was not associated
      with rampant caries. The duration and frequency of breast feeding during the day
      was also not associated. The habit of allowing infants to sleep with the breast
      nipple in their mouths and the presence of linear hypoplasia were strongly
      associated with rampant caries. Odds ratios for these variables were 17.8 and
      15.6 respectively. Based on these associations it is concluded that rampant
      caries in this sample was caused by the habit of allowing infants to sleep with
      the breast nipple in their mouths, whereas linear hypoplasia is considered to be
      a predisposing factor.

PMID- 7813179
TI  - Relationship of gingival calculus and bleeding on probing in CPITN code 2
      sextants.
AB  - The aims of this study were twofold: firstly, to evaluate the relationship of
      supra- or subgingival calculus and bleeding on probing (BOP) in sextants coded 2
      in the Community Periodontal Index of Treatment Needs (CPITN); and secondly, to
      compare the differences in four investigations in Taiwan, Hong Kong, Japan and
      Norway. In a national survey, a total of 2658 Chinese dentate adults were
      examined by using modified CPITN in the Taiwan area from 1985 to 1987. Sextants
      given Code 2 were divided into four subclassifications: supragingival calculus
      with bleeding (I+), supragingival calculus without bleeding (I-), subgingival
      calculus with bleeding (II+) and subgingival calculus without bleeding (II-). The
      results showed that of the 9394 sextants given Code 2, the highest percentage
      (70%) were characterized by the presence of subgingival calculus with bleeding
      and the lowest percentage (4%) by supragingival calculus with bleeding. The ratio
      of sextants coded 2 with only supragingival calculus versus subgingival was
      1:6.2. The bleeding to nonbleeding ratio of sextants coded 2 in this study was
      similar to the Hong Kong study. However, differences among Taiwan, Japan and
      Norway were found. The results indicated that sextants with subgingival calculus
      had a higher tendency to BOP, with a ratio of 4:1. Those with supragingival
      calculus had a ratio of 3:7. We conclude therefore, that it is essential to scale
      teeth to remove subgingival calculus for determination of the necessity of
      periodontal treatment.

PMID- 7813181
TI  - Reasons for extraction of permanent teeth in Japan.
AB  - Eight hundred forty-nine Japanese dentists were asked to record the reason for
      every tooth extraction of permanent teeth during 1 week in each of four seasons.
      The reasons were assigned to six groups: dental caries, periodontal disease,
      eruption problems, trauma, orthodontics and other reasons. Thirty-eight to 40% of
      the dentists returned the forms in each season, relating to a total of 11,175
      extracted teeth. Overall, caries was the most frequent reason for tooth
      extraction (55.4%), followed by periodontal disease (38.0%). The females lost
      more teeth due to caries than did the males. In the > or = 16 age groups, caries
      was the main reason for tooth extraction. However, periodontal disease became
      principal only in the males aged 46-65 yr. Anterior teeth, especially in the
      mandible, represented the highest percentage of periodontal extractions. A
      considerable difference in the major reason for maxillary tooth loss was observed
      between both sexes. Maxillary premolars and molars in the males were extracted
      for periodontal disease as much as for caries, whereas caries was the predominant
      reason for loss of all maxillary teeth in the females.

PMID- 7813180
TI  - Lifestyle, dental caries and number of teeth.
AB  - All 55-yr-old citizens (n = 1012) of Oulu (a middle-sized Finnish town) were
      invited to a clinical examination; 780 agreed to participate. The associations of
      lifestyle with decayed tooth surfaces and the number of teeth were studied in the
      533 dentate subjects. Measures of lifestyle included dietary habits, a smoking
      habit, alcohol consumption and physical activity. When the associations of dental
      caries with lifestyle, sex, dental health behavior, social class and number of
      teeth were studied by logistic regression analysis, lifestyle was shown to have
      an independent association with dental caries. Further analysis of the data
      showed that dental caries increased with a more negative lifestyle in every
      social class, but most significantly in the lowest. Number of teeth was not
      associated with lifestyle, but subjects with lower social status had fewer teeth
      than those with higher social status. The association of lifestyle with dental
      caries supports the idea that behavior in a broader sense should be taken into
      consideration in caries prevention.

PMID- 7813182
TI  - Oral health status and treatment needs in different age groups in two regions of
      Tanzania.
AB  - The present study was conducted in two regions of Tanzania, where development of
      oral health services is supported by the Danish International Development Agency
      (Danida). The study comprised 6035 subjects in five age groups (5-6 yr, 12 yr, 18
      yr, 35-44 yr, 55+ yr). Data were collected using WHO's survey methodology. Dental
      caries affected the primary dentition of one third to one fourth of the 5-6-yr
      olds and mean dft was less than 1.0 in both regions. DMFT for 12-yr-olds was also
      low (< 1.5 DMFT), but was higher in older age groups, mainly due to more missing
      teeth. The F-component was negligible in all age groups. Treatment need was
      mainly simple fillings and extractions. Most periodontal sextants in all age
      groups were affected by bleeding or calculus. Periodontal pockets were rare and
      loss of teeth limited. It is concluded that the oral health situation in Tanzania
      is better than that foreseen in the goals for oral health in Tanzania in the year
      2002. On the basis of these findings and the severe economic constraints
      prevailing within the health services in Tanzania, a revision of The National
      Plan for Oral Health seems urgent. A realistic estimate of the cost and the
      possible sources of funding of the plan is mandatory.

PMID- 7813183
TI  - Dental caries status of 12-year-old students in the state of Mexico.
AB  - A total of 2275 schoolchildren 12 yr of age from the four health regions of the
      State of Mexico were examined for the prevalence and severity of dental caries.
      The proportion of caries-free children was only 10%, and the DMFS index was 6.94.
      78% of the index derived from decayed surfaces, and 19% from filled surfaces.
      Pits and fissures of the permanent first molars were the most frequently affected
      surfaces. Higher dental caries scores were found in rural areas compared with the
      urban centers. No significant relationship was found between use of dentifrice
      and dental caries. Several reasons for this lack of relationship are discussed.
      10% of the children account for 23% of the DMFS index. Results indicate the need
      to aim preventive and restorative programs at the whole population as well as at
      specific high risk groups or individuals.

PMID- 7813184
TI  - Relationship between wearing a removable partial denture and satisfaction in the
      elderly.
AB  - Natural dentitions of elderly people are often reduced, remaining teeth heavily
      restored and removable partial dentures (RPD's) frequently used to replace absent
      teeth. Lack of knowledge exists on how the elderly experience the comfort of
      these replacements. To get more insight 320 dentate noninstitutionalized subjects
      between 55 and 75 yr of age were clinically examined and interviewed by means of
      a questionnaire. Data showed that only 13% of the subjects had a complete
      dentition from the right to the left first molar; 50% had less than four occlusal
      units. 39% of the subjects was wearing a RPD. Analysis showed that subjects with
      a RPD were in general less satisfied with their dental state than subjects
      without a partial denture. However, when the RPD added occlusal units to the
      dentition, satisfaction increased significantly. No differences in satisfaction
      were found between subjects with a metal frame prosthesis and an acrylic denture,
      nor between tooth-bounded and distal extension prostheses. The conclusion can be
      drawn that the indication for a RPD should be limited in elderly people, unless
      the RPD increased the number of the occlusal units.

PMID- 7813185
TI  - Relative value of dental procedures.
AB  - This study was conducted to develop a relative value method for dental
      procedures, and to evaluate the differences in values assigned by private and
      public sector dentists. Samples of 90 general practitioners and 120 clinical
      specialists were systematically drawn to represent all actively working Finnish
      dentists. The dentists were asked to assess the required time and know-how for
      performing various procedures compared to performing a two-surface amalgam
      filling (AF2). At the end, the dentists were asked to divide the value of 200
      between time and know-how for the reference procedure (AF2). These figures were
      then utilized to calculate the average relative value for each procedure. Private
      practitioners' weighted relative values were 55.3% higher than the prices, and
      among public sector dentists they were 27.9% higher. Overall, know-how
      constituted more of the total value of the procedures than did time. Private
      practitioners' time assessments correlated well (r = 0.72-0.95) with the
      recommended prices. However, significant differences were often observed both in
      time and know-how assessments of individual procedures. Both time and know-how
      seem to be important factors when determining values for dental services. For
      evaluation of the value of output in the private sector, the use of prices is
      justified. However, when the productivity of non-profit dental offices is
      evaluated, a value system which is not based on market prices is needed.

PMID- 7813186
TI  - Effectiveness of a personalised referral letter following orthodontic screening.
AB  - No data exist on the usefulness of orthodontic screening in guiding those
      children who need orthodontic treatment towards professional advice. This study
      evaluated the effectiveness of a personalised referral letter following an
      orthodontic screening programme employing an objective measure of treatment need,
      the Index of Orthodontic Treatment Need (IOTN). Out of a total sample of 924
      children aged 11-12 yr, 201 were in need of orthodontic treatment and no
      orthodontic treatment was planned. From this subsample test and control groups
      matched for sex, socio-economic background, dental disease and aesthetic
      impairment were created. Following screening, the parents of the test group only
      were sent a specific orthodontic referral letter. The dental practitioners of the
      children in the test and control groups were contacted during a follow-up
      investigation carried out 8 months later, this revealed that significantly more
      children entered orthodontic treatment pathways from the test group. This study
      demonstrated that a screening programme, using IOTN as a screening test, and a
      referral procedure which provided parents with specific information were
      successful in guiding over one third of children with a need for orthodontic
      treatment towards orthodontic advice.

PMID- 7813187
TI  - Role of health beliefs in patient compliance with preventive dental advice.
AB  - Lack of patient compliance with health recommendations is a well known fact. What
      is less well understood are the reasons why. This study used the Health Belief
      Model (HBM) to investigate the role of patients' health beliefs in patient
      compliance with preventive dental advice. A questionnaire was constructed to
      explore the four beliefs of "seriousness", "susceptibility", "benefits" and "self
      efficacy" and this was administered to 43 adult patients attending the
      conservation department of a large teaching hospital for routine examination.
      Patients were seen twice, 1 month apart. At visit one, plaque was disclosed and
      plaque and bleeding scores were recorded. Patients were taught the modified Bass
      technique of plaque removal. Plaque and bleeding scores were repeated on visit
      two, 1 month later. Compliance was defined as any reduction in these scores at
      visit two. The health belief of "benefits" taken as a single variable showed a
      significant correlation with compliance and the combined beliefs of
      "susceptibility" and "benefits" were also found to be significantly related to
      compliance.

PMID- 7813189
TI  - Household utilization of dental services in Ibadan, Nigeria.

PMID- 7813188
TI  - Social network, social support and dental status in elderly Swedish men.
AB  - The objective of this study was to investigate whether there were associations
      between different aspects of social network and social support and dental status.
      The study sample (n = 621) comprised a random half of all male residents in
      Malmo, Sweden, born in 1914. Five hundred (80.5%) participated. Eight
      conceptually different aspects of social networks and social support were
      measured, and all men were clinically examined regarding number of teeth,
      prevalence of removable dentures, fixed bridges and anterior open tooth spaces.
      We found that some aspects of dental status were associated with social class,
      while others were associated with different aspects of social network and social
      support. Prevalence of complete dentures and fixed bridges was strongly
      associated with social class, a low number of functioning teeth was associated
      with both low social class belonging and an insufficient social network and
      social support, while anterior open tooth spaces were associated mostly with an
      insufficient social network and social support. This study shows that there are
      significant associations between some aspects of dental status and the social
      network and social support of the individual, while other aspects of dental
      status are associated with social class, which from a psychosocial perspective
      contribute to a deeper understanding of the backgrounds of dental status.

PMID- 7813190
TI  - Dental caries prevalence of 6-14-year-old children in Guangdong, China.

PMID- 7813191
TI  - Production and comprehension of referential pointing by orangutans (Pongo
      pygmaeus).
AB  - We report 3 studies of the referential pointing of 2 orangutans (Pongo pygmaeus).
      Chantek was raised in an enculturated environment; Puti, raised in a nursery, had
      a more typical captive life. In Experiment 1, flexibility of pointing behavior
      was investigated by requiring subjects to point in novel circumstances (for an
      out-of-sight tool, not food). In Experiment 2, we investigated the orangutans'
      comprehension of the significance of a human point in helping them to locate
      food. In Experiment 3, we investigated whether these pointing subjects
      comprehended that a human recipient must be looking for the point to achieve its
      attention-directing goal. In all experiments the enculturated orangutan showed
      better understanding of pointing than the captive orangutan. This finding is
      consistent with recent studies that have found differences in the cognitive and
      social-cognitive abilities of apes that have had different types of experience
      with humans.

PMID- 7813192
TI  - Marmoset (Callithrix jacchus jacchus) spatial memory in a foraging task: win-stay
      versus win-shift strategies.
AB  - The spatial memory of common marmosets (Callithrix jacchus jacchus) was explored
      in 3 experiments with a simulated foraging task. In Experiment 1, individual
      monkeys foraged among 8 baited food sites. They appeared to use spatial memory to
      accurately avoid revisiting previously depleted sites. There was no difference in
      accuracy between the adult monkeys and a juvenile monkey tested on the same task.
      In Experiment 2, a win-stay paradigm was used. The adult monkey subject very
      accurately remembered locations that had previously contained food. The monkey
      tended to visit adjacent correct sites when retrieving food and thus minimized
      the total distance travelled. In Experiment 3, a win-shift paradigm was used with
      2 adult monkeys. Although both monkeys performed at above-chance levels of
      accuracy on the win-shift task, they made many errors. These results suggest that
      marmosets may prefer tasks that require a win-stay strategy.

PMID- 7813193
TI  - Evidence for spatial working memory in honeybees (Apis mellifera).
AB  - Spatial working memory (the ability to represent multiple locations in a
      flexible, dynamic manner) has been studied in a range of vertebrate species. The
      results of 3 experiments indicate that this ability also exists in at least one
      invertebrate (honeybees; Apis mellifera). Individual honeybees collected sugar
      solution from a matrix of 6 locations. They avoided revisits to locations
      previously depleted of solution more accurately than expected by chance. The
      results rule out several nonmemorial explanations for this ability, and it is
      therefore best explained by a spatial working memory system that allows
      discrimination of previously visited locations from those not yet visited. These
      results substantially expand the range of species in which spatial working memory
      has been demonstrated.

PMID- 7813194
TI  - Automated recording of individual performance and hand preference during joystick
      task acquisition in group-living bonnet macaques (Macaca radiata).
AB  - A microchip that provided a unique identification number was injected into each
      forearm of all 8 members of a bonnet macaque (Macaca radiata) social group. The
      group was then given computer-controlled joystick tasks of increasing difficulty.
      The identification number of the arm used on each trial was input into the
      computer and used to determine individual performance and hand preference in more
      than 23,000 trials. Three subjects reversed hand preference as task difficulty
      was increased over time. All subjects exhibited nearly exclusive use of a single
      hand on the most difficult task; 6 used the right hand, and 2 used the left.
      Daily patterns of joystick activity for the group members differed somewhat from
      that of our individually housed monkeys.

PMID- 7813195
TI  - Performance of four seed-caching corvid species in the radial-arm maze analog.
AB  - Four seed-caching corvid species were tested in an open-room analog of the radial
      arm maze. During Experiment 1, the species more dependent on stored food. Clark's
      nutcrackers (Nucifraga columbiana) and pinyon jays (Gymnorhinus cyanocephalus),
      acquired the task more quickly and to higher accuracy levels than either scrub
      jays (Aphelocoma coerulescens) or Mexican jays (A. ultramarina). During
      Experiment 2, performance after retention intervals was tested. When intervals of
      30-210 min were tested in ascending order, species differences observed during
      acquisition were again obtained. However, when intervals of 5-300 min were tested
      in random order, the species differed only at shorter intervals. During
      Experiment 3, only nutcrackers gave any indication of performing above chance
      after a 24-hr retention intervals. Results support the hypothesis of species
      differences in spatial information processing that correlate with dependence on
      stored food.

PMID- 7813196
TI  - A computerized system for sequential analysis of aggregation of erythrocytes
      under dynamic conditions.
AB  - Aggregation of erythrocytes at hematocrit 5% in plasma, placed in a glass
      chamber, is analyzed under dynamic conditions by transmission of He-Ne laser
      light. The transmitted intensity (TI) signal which contains mean intensity
      superimposed with fluctuations caused by the movement of erythrocytes and formed
      aggregates, is detected by photodiode-amplifier assembly mounted on a stepper
      motor. The alignment of this detector for the maximum TI is achieved by a
      dedicated software. The TI data after A/D conversion is stored in a PC-AT for
      further processing. The parameters, aggregate size index, aggregate sedimentation
      time index, total time taken for completion of the process, process onset time
      index, total number of fluctuations, and asymmetry index are calculated
      sequentially for the entire data. A comparison of these parameters in blood
      samples obtained from healthy and diabetic subjects show the significance of
      these parameters.

PMID- 7813197
TI  - A method for imaging of intracranial EEG electrodes using magnetic resonance
      imaging.
AB  - In this study, we describe a method for imaging intracerebral electrodes within a
      three-dimensional reconstructed image of the brain. A three-dimensional image of
      the brain was reconstructed from serial magnetic resonance images. The locations
      of intracerebral electrodes were determined from anterior-posterior and lateral
      skull X-rays performed after intracerebral electrode implantation. The three
      dimensional reconstruction of the brain including electrode locations was
      displayed using IRIS Explorer Software (Silicon Graphics, Mountainview, CA). This
      method might improve the interpretation of electrical patterns of seizure
      activity recorded from intracerebral electrodes.

PMID- 7813198
TI  - A linear time algorithm for calculation of multiple pairwise kinship coefficients
      and the genetic index of familiality.
AB  - We present an algorithm that calculates the mean kinship coefficient between all
      pairs of individuals in a given set relative to a known pedigree. The time
      required to make the calculations is proportional to the size of the set. The
      constant of proportionality is determined by the number of generations that the
      pedigree spans. A simple alteration to the algorithm allows efficient calculation
      of all pairwise kinship coefficients within a set of individuals.

PMID- 7813199
TI  - An expert system for the analysis and interpretation of evoked potentials based
      on fuzzy classification: application to brainstem auditory evoked potentials.
AB  - EPEXS is an expert system for evoked potential analysis and interpretation (a
      medical examination performed in clinical neurophysiology laboratories), working
      from available clinical records and numerical data extracted from evoked
      potential traces. EPEXS integrates two formalisms of knowledge representation:
      rules and structured objects. The rules represent the elementary concepts
      (shallow knowledge) and include a model of possibility based on the Dubois and
      Prade default reasoning and possibility theory. The structured objects
      (prototypes) are organized as hierarchical taxonomies (underlying knowledge).
      These allow the description of both the objects and their relationships. The
      heuristics used to interpret knowledge are based on two hypotheses: the unicity
      of the pathological process leading to several given symptoms and the progression
      from the general to the specific, leading to the adoption or rejection of a class
      of diagnoses. This avoids the problem of the differential diagnosis. These
      sources of knowledge are used in a dynamical way that could be described as a
      four-step process: acquisition of clinical data in order to define the
      nosological frame of the pathology, production of hypotheses about the nature and
      topography of lesions, interpretation of data in accordance with these
      hypotheses, and finally evaluation of their likelihood. The validation shows that
      EPEXS topographic diagnoses were correct in 100% of cases and 92% of it nosologic
      diagnoses were correct, and no pathological record was interpreted as normal.
      When examined on a given pathology basis EPEXS was not significantly different
      from human experts as regards to performance, specificity, and sensitivity.

PMID- 7813200
TI  - Automatic detection of ventricular tachycardia and fibrillation using ECG
      processing and intramyocardial pressure measurement.
AB  - Ventricular electrograms and intramyocardial pressure signals were recorded in 11
      dogs during sinus rhythm, during paced ventricular tachycardia, and at the onset
      of and during ventricular fibrillation. The autocorrelation function and the
      probability density function of short episodes of the electrograms were analyzed
      off-line on a digital computer. Peak-to-peak values of the intramyocardial
      pressure were calculated during sinus rhythm and during ventricular tachycardia
      and fibrillation. An algorithm was developed to recognize tachycardia and
      fibrillation using the autocorrelation function, the probability density
      function, and the intramyocardial pressure as input signals. Results show that in
      case of sinus rhythm all detection methods are reliable (recognition rate of
      100%). In case of ventricular tachycardia with hemodynamic impairment the
      autocorrelation function is slightly better (66.6%) than the probability density
      function (44.4%). The onset of ventricular fibrillation is sensed in 81.8% of all
      episodes with the autocorrelation function and in 63.6% with the probability
      density function. During ventricular fibrillation this improves, respectively, to
      92.3 and 69.2%. In all previous cases the intramyocardial pressure signal was
      100% reliable. It is concluded that in this arrhythmia model, the sensitivity of
      an automatic ventricular tachycardia/fibrillation detection system was increased
      by combining ECG processing with analysis of an hemodynamic parameter.

PMID- 7813201
TI  - Evaluation of the use of induction in the development of a medical expert system.
AB  - In an earlier study, two medical expert systems for diagnosing thyroid disorders,
      developed by the application of induction on a sample of previously diagnosed
      cases and on expert-generated rules, diagnosed a set of test cases better than an
      expert system developed by the more traditional method of collaboration between a
      knowledge engineer and an expert. In this paper, an alternative measure of the
      accuracy of diagnosis of each system is used to evaluate the systems. Diagnoses
      for every distinct case represented by a combination of indicating factors are
      compared with diagnoses that the expert made. The induced systems provide
      diagnoses for many more distinct cases, but a much higher proportion of these
      diagnoses are incorrect. It is argued that generalizing to unseen cases is an
      inappropriate use of induction algorithms. The systematic development of a
      decision table is a more appropriate method for devising a medical expert system.

PMID- 7813203
TI  - [A discussion on the original theory of "care"--an introduction].

PMID- 7813202
TI  - Decision support in medicine: examples from the HELP system.
AB  - Computerized health information systems can contribute to the care received by
      patients in a number of ways. Not the least of these is through interactions with
      health care providers to modify diagnostic and therapeutic decisions. Since its
      beginning, developers have used the HELP hospital information system to explore
      computerized interventions into the medical decision making process. By their
      nature these interventions imply a computer-directed interaction with the
      physicians, nurses, and therapists involved in delivering care. In this paper we
      describe four different approaches to this intervention. These include: (1)
      processes that respond to the appearance of certain types of clinical data by
      issuing an alert informing caregivers of these data's presence and import, (2)
      programs that critique new orders and propose changes in those orders when
      appropriate, (3) programs that suggest new orders and procedures in response to
      patient data suggesting their need, and (4) applications that function by
      summarizing patient care data and that attempt to retrospectively assess the
      average or typical quality of medical decisions and therapeutic interventions
      made by health care providers. These approaches are illustrated with experience
      from the HELP system.

PMID- 7813204
TI  - [Case study reports, No. 25 (Society for Scientific Nursing)].

PMID- 7813205
TI  - [Searching for logic of children's recognition].

PMID- 7813206
TI  - [My experience working as a 'corporate volunteer'].

PMID- 7813208
TI  - [Beginning course of English medical terminology based on analytical method].

PMID- 7813207
TI  - [What is psychiatry].

PMID- 7813209
TI  - [Asking about 'nursing and medicine'].

PMID- 7813210
TI  - Management of cholelithiasis in heart and kidney transplant patients: with review
      of laparoscopic cholecystectomy.
AB  - The purpose of this study was to determine the incidence of cholelithiasis among
      heart and kidney transplant recipients. Since recommendations for cholecystectomy
      in transplant recipients varies widely, we discuss guidelines for surgery
      including laparoscopic techniques. We reviewed the records of 114 patients who
      underwent heart transplantation from 1984 to 1993 and 539 kidney transplant
      patients from 1972 to 1993. Recipients of heart and kidney transplants were found
      to have an incidence of cholelithiasis of 12% and 3% respectively.
      Pretransplantation ultrasound surveillance was used in heart transplant
      recipients and 64% of these with asymptomatic cholelithiasis have not required
      surgery with close follow-up from six months to six years. Thirty-six percent of
      the heart patients underwent cholecystectomy. All symptomatic renal transplant
      patients undergoing ultrasound with the findings of cholelithiasis underwent
      cholecystectomy. Open cholecystectomies were performed prior to the advent of
      laparoscopic surgery in six of the first seven attempts. Laparoscopic
      cholecystectomy on heart and kidney transplant recipients was well tolerated with
      admission the same day of surgery, a one to two day hospital stay and maintenance
      of oral immunosuppression. There was a single complication of leg
      thrombophlebitis, no mortality, and allograft rejection did not occur.

PMID- 7813211
TI  - How many physicians is enough?: the debate over the supply of United States'
      physicians in context.
AB  - Physician manpower policy is a vital part of current efforts at United States
      health-care reform. The fundamentals of the ongoing debate over the adequacy of
      the national physician supply are: (1) what constitutes an adequate supply of
      physicians? (2) how does one determine if supply will be adequate in the future?
      (3) what are the consequences of having too many or too few physicians? and (4)
      what approaches could be taken to influence the size, specialty composition, or
      geographic distribution of the physician work force? Virtually all forecasts
      agree that the United States faces a future aggregate oversupply of physicians,
      with significant specialty imbalances. With these surpluses come economic costs
      that the nation appears unwilling to assume. Options for bringing physician
      supply into balance with requirements include reducing the numbers of new
      physicians entering active practice, increasing retirements, limiting
      availability of positions in oversubscribed specialties, and encouraging
      physicians to work in underserved areas.

PMID- 7813212
TI  - Human immunodeficiency virus (HIV) infection as a leading cause of death among
      young adults aged 25 to 44 years in Connecticut.

PMID- 7813213
TI  - AIDS in Connecticut, annual surveillance report--executive summary.

PMID- 7813214
TI  - Important principles of effective pain management.

PMID- 7813215
TI  - Don't mourn the death of Health Care Reform.

PMID- 7813216
TI  - Attorney responsibility and tort reform.

PMID- 7813217
TI  - Primary care doctor or generalist?

PMID- 7813218
TI  - Acts of compassion: a response to Dr. Eddy's and Dr. Massey's articles.

PMID- 7813219
TI  - Serum distribution of two contraceptive progestins: 3-ketodesogestrel and
      gestodene.
AB  - A cross-over study of two oral contraceptive formulations, containing 30
      micrograms ethinylestradiol in combination with 150 micrograms desogestrel
      (Marvelon) or 75 micrograms gestodene (Femovan), has been performed to compare
      the serum distribution and pharmacokinetics of gestodene and the active
      metabolite of desogestrel, namely 3-ketodesogestrel. Serum concentrations of both
      sex hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG)
      were also measured and were increased more than 3-fold and 2-fold, respectively,
      on day 21 of the treatment cycle, with no statistically significant difference
      between treatment groups. In addition, 35 days after ingestion of either oral
      contraceptive had ceased, the serum SHBG and CBG concentrations were similar to
      the pretreatment values. During treatment cycles, increased serum SHBG levels
      were associated with a redistribution of 3-ketodesogestrel and gestodene such
      that the non-protein-bound (NPB) and albumin-bound fractions were reduced in
      concert with an increase in the relative proportions bound to SHBG. The
      proportion of gestodene bound to SHBG was consistently higher than that observed
      for 3-ketodesogestrel, and this undoubtedly reflects the higher affinity of SHBG
      for gestodene (Kd = 1.2 nM at 37 degrees C) when compared to 3-ketodesogestrel
      (Kd = 4.7 nM at 37 degrees C). It also probably accounts, in part, for the much
      higher total serum levels of gestodene (8.58 nmol/L) when compared to 3
      ketodesogestrel (2.37 nmol/L) during the treatment cycles. Consequently, the
      absolute amounts of NPB, non-SHBG-bound, and SHBG-bound gestodene are
      significantly higher than those measured for 3-ketodesogestrel. It is concluded
      that ethinylestradiol-induced increases in serum SHBG levels during treatment
      with Marvelon or Femovan, influenced the distribution and total amount of 3
      ketodesogestrel and gestodene in serum, respectively, and that this, combined
      with the higher affinity of SHBG for gestodene, results in a greater amount of
      bioavailable gestodene compared to 3-ketodesogestrel, despite the smaller dose of
      gestodene administered.

PMID- 7813220
TI  - Effect of prophylactic antibiotics on morbidity associated with IUD insertion:
      results of a pilot randomized controlled trial. IUD Study Group.
AB  - The efficacy of administering an antibiotic prior to IUD insertion to reduce the
      risk of introducing an upper genital tract infection during the procedure has not
      yet been established. Two double-blind randomized studies conducted in Africa
      comparing a 200 mg prophylactic dose of doxycycline with a placebo did not
      conclusively identify a reduced risk of post-insertion pelvic inflammatory
      disease (PID). A clinical trial of comparable design is currently under way in
      the US. This multi-site trial will evaluate whether use of an antibiotic prior to
      insertion reduces the risk of IUD removal for all medical reasons, including
      upper genital tract infection, within the first three months after insertion.
      This paper reports on the pilot phase of this study, which was designed to test
      the protocols and data collection instruments in advance of the full-scale
      clinical trial. A total of 447 prospective IUD (TCu-380A) users were randomly
      assigned to receive either a 200 mg dose of doxycycline or a placebo one hour
      before IUD insertion. 3.6% (8/219) of participants who received the antibiotic
      had the device removed for medical reasons (infection, bleeding, cramping, etc.)
      within three months post-insertion compared to 4.5% (10/223) of participants who
      received the placebo. This reduction in the removal rate was not statistically
      significant given the limited size of the pilot study (RR = 0.81; 95% CI 0.28
      2.29). Only two subjects, one from each treatment group, met the diagnostic
      criteria for acute PID. The overall three-month retention rate was 91.8% for the
      antibiotic group and 89.7% for the placebo group.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7813221
TI  - Multicentred, phase III clinical trial of norethisterone enanthate 50 mg plus
      estradiol valerate 5 mg as a monthly injectable contraceptive; final three-year
      report.
AB  - Norethisterone enanthate (NET-EN) 50 mg combined with estradiol valerate (EV) 5
      mg was studied as a once-a-month injectable contraceptive with regard to
      effectiveness, cycle control, adverse events and acceptability. In eight Family
      Planning Centres from five Latin American countries, 931 fertile women were
      followed-up for a period of 36 months, providing a total of 15,787 woman-months
      of experience. Only one pregnancy occurred: in the first treated month a few days
      before the second injection (failure rate 0.08 per 100 woman-years). Under
      treatment, the first cycle was drastically shortened in most cases, but
      thereafter cycles tended to recover to pre-treatment patterns. There was a
      significant decrease of hypermenorrhoea and dysmenorrheic cycles. Intracyclic
      bleeding and spotting appeared in 1.8% and 2.2%, respectively, and amenorrhea in
      2.8% of cycles. The incidence of other adverse events was very low with the
      exception of weight gain of more than 2 kg (36.8%). The continuation rate at 12
      months was 64.7%, at 24 months 31.0% and at 36 months 20.4%. The cumulative
      discontinuation rate due to bleeding problems was 6.1% and 7.2% due to adverse
      events at 36 months. The treatment was shown to be a highly effective
      contraceptive method that offers fairly good cycle control, good tolerance and a
      continuation rate that makes it suitable for use in family planning programmes in
      the Latin American area.

PMID- 7813222
TI  - An analysis of the personal reasons for discontinuing IUD use.
AB  - The objective of this study was to evaluate possible factors associated with
      discontinuing use of TCu 380A IUDs due to personal reasons among 2748 users.
      Overall, a total of 88 subjects discontinued using the TCu 380A IUD within 12
      months postinsertion for personal reasons. The most common reasons were planned
      pregnancy (32%) and husband or family opinion against IUD use (26%). The gross
      cumulative 12-month life table discontinuation rate for all personal reasons was
      4.0 per 100 women. Having no education and/or living in a rural area were the
      sociodemographic characteristics associated with an increased risk of
      discontinuation for personal reasons. Effective and regular counseling about IUD
      use, especially among illiterate women, may help prevent IUD discontinuations
      related to personal reasons.

PMID- 7813223
TI  - Norplant contraceptive acceptability among women in five Asian countries.
AB  - An analysis of 1,882 Asian acceptors of Norplant implants indicates that method
      acceptability remained high among the 882 women who used the method for five
      years. Women who discontinued early from the study were, on average, younger than
      those who completed five years of use. Also, they had fewer live births and were
      more likely to desire additional children. Overall, about 70% of the women in
      these countries found the Norplant implant method to be very favorable. The
      majority (> 40%) of the women found the ease and duration of use of the method to
      be most attractive, while menstrual disturbances were the least-liked aspect of
      the method. Although it was apparent that there are still some potential
      obstacles to Norplant implant acceptance, most noticeably concerns about
      menstrual irregularities, interest in continuing the method after five years of
      use is high. Further research of issues related to Norplant implant acceptability
      may improve continuation rates and overall client satisfaction.

PMID- 7813224
TI  - The use of modern and traditional methods of fertility control in Bangladesh: a
      multivariate analysis.
AB  - An attempt has been made to study the use pattern of traditional and modern
      methods of fertility control among currently married women of reproductive ages
      utilizing the 1989 BFS data. Bivariate analysis has been employed to study the
      differentials in the use pattern by some selected demographic and socio-economic
      characteristics. Also, multivariate logistic regression analysis has been used to
      identify independent contributions of each selected covariate. It has been
      observed, however, that there is universality of knowledge about contraceptive
      methods. Of the total 31 percent, about 23 percent were using modern methods and
      the rest, 8 percent, traditional methods. Analysis using a logistic regression
      model showed that visits of family planning workers have very strong and positive
      influence on the current use of modern contraceptives as compared to traditional
      methods. Duration of effective marriage also emerged as a strong determinant of
      modern versus traditional methods use but it influenced modern methods use
      negatively. Also, administrative division is an important variable. Residents of
      Rajshahi division were significantly more (relative odds of 2.5) likely to be
      using modern methods than residents of Chittagong division. The likelihood of
      women having electricity in their household of being a current user of modern
      contraceptives is almost 2 times higher compared to women without electricity in
      their households. Education and occupation of husbands also exerts effect on
      current use of modern contraceptives. The odds of current use of modern methods
      among women whose husbands have secondary and higher level of education is one
      and-a-half times higher than that of women with husbands having no formal
      education. However, wives of landowners were less (relative odds of 0.72) likely
      to use these methods as compared to traditional methods than wives of labourers
      or farmers. The probability of current use of modern contraceptives was higher
      (relative odds of 1.5) among women who discussed family planning with their
      husbands than those who did not.

PMID- 7813226
TI  - Pressor responsiveness in rats with hypertension induced by mestranol.
AB  - The aim of this study was to determine if pressor hyper-responsiveness is
      associated with the hypertension that results from the ingestion of the synthetic
      estrogen, mestranol. Rats were fed a diet containing mestranol for 6 months,
      while control rats were fed the same diet without mestranol. Catheters were then
      placed in the carotid artery and jugular vein of all rats, under halothane
      anesthesia. When the rats had recovered from the anesthesia, blood pressure was
      measured through the carotid catheter in conscious rats. Each rat received IV
      injections of norepinephrine (NE) at 2, 4, 8, and 16 ng per 100 gm body weight,
      and the pressor responses were recorded. The rats fed mestranol had significantly
      higher arterial pressures than did the control rats. However, the pressor
      responses to NE were significantly less in the mestranol-treated rats than in the
      controls, indicating that pressor hyper-responsiveness does not contribute to
      this form of hypertension.

PMID- 7813225
TI  - The effects of CTR-24, a biphasic oral contraceptive combination, compared to
      Diane-35 in women with acne.
AB  - One-hundred-and-eighty-three women were enrolled in an open, randomized,
      multicentre study in which the effects on acne of a low-dose biphasic oral
      contraceptive containing a daily dosage of 25 micrograms desogestrel and 40
      micrograms ethinylestradiol (7 days) and a daily dosage of 125 micrograms
      desogestrel and 30 micrograms ethinylestradiol (15 days) were compared to Diane
      35 containing a daily dosage of 2.0 mg cyproterone acetate and 30 micrograms
      ethinylestradiol (21 days) during four cycles of treatment. Clinical and
      photographic evaluation of acne plus laboratory assessments were done before
      treatment and at the end of cycle 4. A reduction with regard to the number of
      lesions and the degree of severity was observed in both groups. No differences
      were found between the two treatments in the clinical and photographic
      evaluation. In both treatment groups, a decrease in total testosterone and 3
      alpha-17 beta-androstanediol glucuronide was observed and an increase in SHBG.
      The decrease in 3 alpha-17 beta-androstanediol was statistically significantly
      more pronounced in the Diane-35 group.

PMID- 7813227
TI  - Biochemical studies of the effect of gossypol consumption on cholesterol and
      residual glucose in fed and protein-energy deficient rats.
AB  - Some biochemical parameters were investigated on gossypol consumption, and were
      correlated to the level of cholesterol and residual glucose in rat liver. Two
      groups of animals were used, one group was fed with normal protein diet and the
      other set was fed with low protein diet. The results show that gossypol produced
      no apparent biochemical aberration in the liver of normal protein fed and low
      protein fed rats. It also had no effect on glucose-6-phosphatase and prostate
      phosphatase. Gossypol consumption had a significant effect on alcohol
      dehydrogenase. These results indicate no direct involvement of gossypol in sugar
      uptake but profound influence on the regulation of cholesterol level in the
      liver.

PMID- 7813228
TI  - Radionuclide assessment of ventricular function.

PMID- 7813229
TI  - Clinical and exercise test markers of prognosis in patients with stable coronary
      artery disease.
AB  - Current management of coronary artery disease has taken a very aggressive
      approach in which cardiac catheterization plays a prominent role in patient
      evaluation and in which bypass and angioplasty are commonly used for therapy. The
      number of cardiac catheterizations and procedures, not surprisingly, have grown
      in tandem because angiography provides anatomic information that becomes the
      substrate for justifying interventions. Bypass surgery has been shown to confer a
      survival benefit compared with medical therapy in patients with multiple-vessel
      disease and left ventricular dysfunction, but it also is still used in other
      patient populations with equivocal indications. Comparison studies of
      percutaneous transluminal coronary angioplasty with medical management have
      indicated a slight advantage with percutaneous transluminal coronary angioplasty
      in limiting symptoms, but no evidence yet supports its survival benefit.
      Angioplasty, however, has become much more common in the last decade,
      particularly as the initial revascularization technique. Because cardiac
      catheterization is frequently the nodal branch point between invasive and
      noninvasive (i.e., medical) management, its application should be limited to high
      risk candidates who would receive a survival benefit from these procedures or to
      those with intractable symptoms. Those who propose that catheterization is the
      best method for risk stratification argue that noninvasive testing requires
      physiologically significant disease and that morbid or fatal events can occur
      with rapid progression of minimal disease. From the studies reviewed, however,
      the extent of coronary angiographic disease is not clearly predictive of future
      cardiovascular events. Although some studies found the number of diseased vessels
      to be independent prognostic variables, most found that it did not add any
      additional prognostic information beyond that provided from noninvasive testing.
      Furthermore, there has been an argument that silent ischemia puts patients at
      higher risk of sudden death or infarction, and these patients need to be
      catheterized. However, numerous studies have shown that this concern is
      exaggerated. The studies reviewed found that except for patients with diabetes,
      those with "silent" or painless exercise-induced ST depression do not have a
      worse prognosis than those with symptomatic ST depression when cardiovascular
      death, sudden death, or acute myocardial infarction are considered Clinical and
      exercise test variables have been underused in estimating prognosis.
      Specifically, they are rarely used systematically to stratify patients into low
      risk groups who do not need catheterization and high-risk groups who should
      undergo angiography because of possible lesions amenable to bypass or
      angioplasty.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7813230
TI  - Bacterial meningitis in children: current concepts of neurologic management.

PMID- 7813231
TI  - Contact allergy in children. Part I: Rubber allergy.

PMID- 7813232
TI  - A dermatologic diary. Portrait of a practice.

PMID- 7813233
TI  - Knuckle pads.
AB  - Knuckle pads are well circumscribed thickenings of the skin over the
      metacarpophalangeal and, more commonly, the proximal interphalangeal joints.
      Although the association with several other clinical syndromes including
      Dupuytren's disease is well documented, most cases are idiopathic. We present a
      case of knuckle pads and briefly review the history and course of this disease.

PMID- 7813234
TI  - Incontinentia pigmenti: clinicopathologic characteristics and differential
      diagnosis.
AB  - A newborn girl had erythematous-based vesicles and pustules on her chest and
      extremities and eosinophilia. Within two weeks, she also showed linear verrucous
      plaques on her arms and legs. Pathologic evaluation of the skin lesions confirmed
      the clinically suspected diagnosis of incontinentia pigmenti. Results of
      subsequent neurologic, ophthalmologic, and pediatric evaluations have been normal
      without the detection of potential incontinentia pigmenti-associated systemic
      manifestations. The clinical and pathologic features of incontinentia pigmenti
      skin lesions are reviewed and the systemic manifestations summarized.

PMID- 7813235
TI  - Persistent light reaction with erythroderma caused by musk ambrette: a case
      report.
AB  - Persistent light reaction is an uncommon type of photodermatitis caused mainly by
      musk ambrette, a synthetic fragrance material commonly used in foods and
      cosmetics. Erythrodermic persistent light reaction is rare. We report a case of
      erythroderma with underlying persistent light reaction due to musk ambrette. A 71
      year-old man showed a photodermatitis that waxed and waned for five years before
      it became more persistent and finally evolved into erythroderma. Positive results
      of a photopatch test to musk ambrette and a low minimal erythema dose to
      ultraviolet B were noted. A biopsy specimen of the erythrodermic lesion revealed
      spongiotic dermatitis. The erythroderma and photodermatitis responded to systemic
      steroids and psoralen/ultraviolet A therapy (total dose: 90 J/cm2). We suggest
      that persistent light reaction be included in the differential diagnosis of
      erythroderma.

PMID- 7813236
TI  - Better dermatologic office photography: getting started.
AB  - In an earlier paper, we defined a medical photograph as one that accurately
      maximizes clinical information while minimizing irrelevant data. This paper
      expands on this concept, providing specific hints to assist the practitioner in
      obtaining consistent high-quality clinical photos. We review the important
      question every medical photographer must ask when looking through the viewfinder
      as well as the difference between photography for practitioners of plastic
      surgery and dermatology.

PMID- 7813237
TI  - Autoimmune progesterone dermatitis treated with tamoxifen.

PMID- 7813238
TI  - Eccrine poroma in an unusual location.

PMID- 7813239
TI  - Parmesan cheese and vegetable-induced histaminuria in a thermal flusher.
AB  - Flushing disorders are associated with sweating (wet flushes) or without sweating
      (dry flushes). When associated with systemic symptoms and histaminuria, flushing
      reactions may easily be confused with mastocytosis or pheochromocytoma. We report
      a case of a woman with significant transient histaminuria that could be
      dissociated from episodes of thermal wet flushing. Treatment with clonidine led
      to a decrease in both frequency and intensity of the flushing reactions.

PMID- 7813240
TI  - Costochondritis presenting as a peculiar skin lesion.
AB  - Costochondritis is an important complication of median sternotomy that can
      present months to years after surgery. Delay in diagnosis may result in more
      disability and increased medical costs. The varied clinical manifestations of
      costochondritis are reviewed and a case is presented.

PMID- 7813241
TI  - Focal myositis in a patient with bilateral painful nodules.
AB  - A 30-year-old African-American man presented with painful lower extremities and
      bilaterally symmetrical dermal nodules. Examination of a biopsy specimen of one
      of the nodules showed focal myositis overlying a deeper defect. Subsequent
      excisions produced multifocal eruptive lipomas. The histopathologic findings of
      focal myositis are reviewed along with this previously unreported association.

PMID- 7813242
TI  - Acute generalized exanthemic pustulosis.
AB  - Acute generalized exanthemic pustulosis often presents dramatically with the
      abrupt onset of a widespread pustular eruption on an erythematous base, with a
      frequently positive Nikolsky sign. In most cases, penicillins or macrolides are
      causally related. The main differential diagnosis of a generalized pustular
      eruption in a febrile patient is pustular psoriasis, which can be differentiated
      on both a clinical and histologic basis.

PMID- 7813243
TI  - Basal cell carcinoma simulating eczematous dermatitis.
AB  - Superficial basal cell carcinoma typically presents as an erythematous, scaling,
      mildly infiltrated patch, which may have a "pearly" border. Because these lesions
      share some of the clinical features of dermatitis, they are occasionally
      misdiagnosed for many years. We report a case of basal cell carcinoma of thirteen
      years' duration that presented clinically as eczematous dermatitis. We believe
      that this reaffirms the importance of histologic examination of longstanding skin
      lesions that fail to respond to standard therapy.

PMID- 7813244
TI  - Pustular mycosis fungoides.
AB  - The clinical presentations of cutaneous T-cell lymphoma (mycosis fungoides) are
      quite variable. Atypical manifestations of cutaneous T-cell lymphoma include
      bullous, granulomatous, hypopigmented, verrucous, and pustular variants. We
      report a patient who had a psoriasiform dermatitis of the palm and soles which
      showed pustulation.

PMID- 7813245
TI  - Schamberg's purpura: association with persistent hepatitis B surface antigenemia
      and treatment with pentoxifylline.
AB  - A 54-year-old man experienced an extensive asymptomatic purpuric eruption on both
      his legs consistent with Schamberg's purpura. Three months before, he had had an
      episode of acute viral hepatitis. Nine months later, the purpura was unchanged
      despite administration of a topical corticosteroid. Results of serologic
      evaluation revealed hepatitis B surface antigen. The patient was treated orally
      with pentoxifylline, 400 mg three times daily. After one month of therapy, the
      purpuric elements of his eruption had disappeared, and after two additional
      months most of the pigmentation had also faded.

PMID- 7813246
TI  - Successful treatment with fluconazole of tinea corporis caused by Trichophyton
      verrucosum (barn ich).
AB  - A student in a veterinary program noted an inflammatory tinea corporis on the
      right forearm after working with cows. Culture grew Trichophyton verrucosum. A
      nine-day course of treatment with oral fluconazole, 100 mg daily, resulted in
      prompt resolution. Awareness of the clinical presentations of barn itch, and
      familiarity with wet mount and histopathologic features, and special growth
      requirements of T. verrucosum will facilitate prompt diagnosis and treatment.
      Therapy with newer antifungal agents such as fluconazole may offer advantages
      over grisefulvin.

PMID- 7813247
TI  - Esophageal and small intestinal manifestations of progressive systemic sclerosis.
      A clinical and experimental study.
AB  - Progressive systemic sclerosis (PSS) is a systemic disease with a high frequency
      of gastro-intestinal involvement. The present thesis deals with the occurrence
      of, the complications to, and the treatment of the esophageal manifestations
      combined with more experimental studies on small intestine manifestations. The
      conclusions in this thesis are based on results achieved in 9 original previously
      published papers. The pattern of esophageal dysmotility is thoroughly evaluated
      in 156 consecutive PSS patients and is found to be identical to what is found in
      other large series of PSS patients. In paper no. I dysmotility variables are
      correlated to the occurrence of gastroesophageal reflux (GER) and it is shown
      that also in this group of patients with well defined dysmotility problems the
      only reliable GER test is pH-metry. Esophageal dysmotility furthers esophageal
      candidosis, which is further facilitated by anti-reflux treatment. This problem
      is evaluated in paper no. V. Progression of esophageal dysmotility in spite of D
      penicillamine treatment is shown in paper no. VII and confirms the non-stable
      condition of the PSS patient in regard to esophageal manifestations and
      complications. This point is also outlined in paper no. IX concerning
      surveillance and continuous treatment of esophageal PSS. Esophageal stricturing
      is a well-known entity in PSS. The etiologic question of esophageal stricturing
      being a manifestation of PSS and/or a peptic complication, is approached in paper
      no. VIII. PSS manifestations of the small intestine are not as frequent as in the
      esophagus, in the present material only 19% presented with X-ray changes.
      However, bacterial count of duodenal juice as an indirect measurement of small
      intestinal dysmotility in paper no. VI indicates a much larger percentage of
      small intestinal involvement than revealed by X-ray. In paper no. VI the exocrine
      pancreatic function was assessed in 16 PSS patients. It is shown that the
      endogenous stimulation capacity is preserved even in spite of demonstrable small
      intestinal PSS involvement and that exocrine pancreatic function is frequently
      reduced, but rarely to a degree of clinical significance. Small intestinal
      enterocyte function is evaluated according to the ability to hydrolyse
      folatepolyglutamates and to absorb D-penicillamine, and is in both respects found
      less than normal. In an ultrastructural evaluation (paper II) the enterocytes
      presented signs of defective fat transport. PSS manifestations of the
      gastrointestinal tract are frequent and burdensome to the patient. Omeprazole and
      new prokinetic drugs have rendered new therapeutic potentialities, which,
      however, more than ever demand constant surveillance and individualized
      regulation of treatment.

PMID- 7813248
TI  - Prediction, measurement and clinical significance of yellow skin colour in mature
      healthy neonates.

PMID- 7813249
TI  - Gastrointestinal transit measurements. A scintigraphic method.

PMID- 7813250
TI  - Impact of hormone replacement therapy on serum lipids, lipoproteins, body
      composition, and atherosclerosis: clinical and experimental studies.

PMID- 7813251
TI  - Mechanisms of cell damage and enzyme release.
AB  - Release of intracellular enzymes to the extracellular space is a marker of cell
      damage in various diseases, e.g. liver, heart and muscle diseases. In the normal
      state the plasma membrane is impermeable to enzymes, and enzyme release,
      therefore, indicates a severe change of the membrane integrity. This review deals
      with the present knowledge about cellular changes leading to enzyme release,
      which may be caused either by energy depletion, e.g. in ischemia or shock, or by
      a direct membrane damage as caused by various toxins and inflammatory products.
      Inhibition of the energy metabolism results in ATP depletion leading to fluxes of
      Na+, K+ and Cl- down their gradients across the membrane and swelling of the
      cell. Subsequently Ca2+ leak into the cell activating phospholipases and the
      formation of eicosanoids, affecting the cytoskeleton and, perhaps, activating the
      formation of oxidants. The exact "point of no return" is not known but an
      uncontrolled Ca2+ activity in the cell probably has an important role in
      initiating the irreversible changes. The result of these reactions and probably
      other unknown reactions as well is damage to the membrane. This is evident
      morphologically at first by the formation of blebs that appears in the reversible
      phase, and later on by rupturing of the membrane, a sign of irreversible damage.
      A very small part of the enzyme release may occur in the reversible phase when
      blebs detach with resealing of the membrane, but the substantial part of enzyme
      release occurs as a result of irreversible cell damage when ATP has decreased to
      a low level and a serious disruption of the membrane integrity has taken place.
      All the secondary affections of the membrane during energy depletion may also
      occur as a primary direct membrane damage that more or less may affect the energy
      metabolism secondarily. The cell damage and enzyme release after some types of
      direct membrane damage is almost independent of the cellular energy metabolism
      whereas other types of direct membrane damage are counteracted by the cell by
      energy consuming reactions and, therefore, the final cell damage is a concerted
      action of the direct membrane damage and the energy depletion. This also means
      that a direct membrane damage may be more severe for the cell in energy depleted
      states than in the normal state. As in energy dependent cell damage the
      substantial part of enzyme release after a direct membrane damage is due to
      irreversible cellular changes. It appears that although the knowledge of the
      molecular basis of cell damage and enzyme release has grown there are still many
      questions to be answered about these complex processes.

PMID- 7813252
TI  - Neuronal plasticity and pre-emptive analgesia: implications for the management of
      postoperative pain.
AB  - Prevention of injury-induced functional alterations in the central nervous system
      by pre-emptive analgesia or other techniques is a fascinating working hypothesis
      based on substantial scientific evidence. Although experimental data may provide
      a rationale for this concept, translation into clinical practice has led to some
      debate, especially about interpretation of results from studies in postoperative
      patients (Katz et al. 1992a, 1993; Dahl et al 1992a, 1993b; Dahl & Kehlet 1993a).
      This may partly be due to a difference in experimental versus clinical benefits
      from pre-emptive analgesia and furthermore, clinicians may ask if preoperative
      administration of morphine or other opioids is really a "novel approach" (Katz
      1993) to the management of postoperative pain. Thus, administration of opioids
      for premedication, and during induction and maintenance of general anaesthesia
      has been common clinical practice for decades. In spite of this practice,
      patients have suffered from unacceptable postoperative pain. Several critical
      elements must be addressed before the concept can be applied into clinical
      practice. Thus, the idea originates from experimental studies, often with
      anaesthetized or decerebrated animals, and with nociceptive stimuli which did not
      involve severe ongoing tissue damage. The various types of noxious stimuli (C
      fiber stimulation, heat-, chemical-, inflammatory- and neuronal lesions) may
      differ from the surgical injury, and the time-scale of the experiments, and the
      profiles of analgesic effects and efficacy may differ from the clinical
      situation. In a study of patients undergoing gynaecological laparotomy, increased
      sensitivity to noxious electrical stimulation of the sural nerve was observed
      postoperatively, with a corresponding trend in the nociceptive flexion
      reflex.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7813253
TI  - Abdominal symptoms, visits to the doctor, and medicine consumption among the
      elderly. A population based study.
AB  - Abdominal symptoms are frequent in the normal elderly population, but only a
      minority contact doctors. The present study was performed to assess the impact of
      abdominal symptoms on primary health care and medicine consumption and, in
      addition, to describe factors that relate to resource consumption. A postal
      questionnaire was mailed to a random cohort of 859 Danish people at the age of
      75. Seventy-nine percent returned the questionnaire. A total of 31% of the men
      and 42% of the women had experienced at least one abdominal symptom within the
      past year. Among these 25% had visited a doctor and a little less had taken
      medicine. The total expenses used on primary health care and medicine were 22,000
      U.S. Dollars per 1000 persons. Factors related to visiting a doctor were not only
      the presence of symptoms but also the subject's concept of the symptom as a
      health problem. As a consequence, efforts to control expenses should also focus
      on why some subjects consider their symptoms a health-problem while others do
      not.

PMID- 7813254
TI  - Plasma cholecystokinin in obese patients before and after jejunoileal bypass with
      3:1 or 1:3 jejunoileal ratio--no role in the increased risk of gallstone
      formation.
AB  - BACKGROUND AND AIM: Jejunoileal bypass surgery for obesity increases the risk of
      gallstone formation, and, contrary to expectations, the incidence is greater in
      patients with a long as compared to a short ileum left in continuity. Impaired
      gallbladder motility due to reduced cholecystokinin (CCK) stimulation could be an
      explanation. The aim of this study was to investigate the CCK levels in such
      patients. SETTING: The randomized trial of bypass surgery named The Danish
      Obesity Project. DESIGN AND METHODS: We compared plasma levels of CCK in obese
      patients at three, nine or 15 months after jejunoileal bypass surgery with either
      a 1:3 jejunoileal ratio (n = 14) or a 3:1 ratio (n = 15), and in unoperated obese
      patients (n = 7). Plasma CCK levels were determined during fasting and during 150
      min following ingestion of a liquid test meal. RESULTS: There were no significant
      changes over time following surgery. Basal CCK levels were significantly
      increased after surgery, and significantly higher in those with a 3:1 than in
      those with a 1:3 jejunoileal ratio. The postprandial AUC (mean +/- SEM) was 935
      +/- 71 pM x min in the 3:1 ratio group and 891 +/- 100 pM x min in the 1:3 ratio
      group. This difference was not significant, but both bypass groups were
      significantly higher than the unoperated group (515 +/- 79 pM x min). The
      integrated increase in plasma CCK above basal level showed a similar pattern, but
      the difference between the unoperated and the bypass groups was insignificant.
      CONCLUSION: Postoperative changes in plasma CCK levels neither explain the
      increased risk of gallstone formation after bypass surgery nor the higher
      incidence with a long compared to a short ileum left in continuity in the bypass.

PMID- 7813255
TI  - Postoperative electrolyte and mineral balance after restorative proctocolectomy
      with ileoanal reservoir.
AB  - Postoperative electrolyte and mineral balance was studied in nine patients with
      ulcerative colitis who underwent restorative proctocolectomy with ileoanal
      reservoir (J-pouch). The study was carried out during the first seven days of
      bowel function after construction of the reservoir and temporary ileostomy, and
      again after the ileostomy was closed and bowel continuity re-established. Stool
      volume and intestinal sodium excretion were reduced by respectively 40 and 45%
      after ileostomy was closed (p < 0.05), but potassium excretion was unchanged. The
      concentration of sodium was higher in ileostomy effluents, whereas the
      concentration of potassium was higher in stools after the ileostomy was closed (p
      < 0.05). Significant changes in blood and urinary electrolytes or minerals were
      not recorded. It is concluded that a major reduction in stool volume and
      intestinal excretion of sodium is already present in the early postoperative
      period after bowel continuity has been re-established.

PMID- 7813256
TI  - Who will teach the medical students?

PMID- 7813257
TI  - Laser-assisted uvulopalatoplasty ... the cart before the horse.

PMID- 7813258
TI  - Transbronchial biopsy in the diagnosis of pulmonary infiltrates in
      immunocompromised patients.
AB  - Bronchoalveolar lavage (BAL) and transbronchial biopsy (TBB) frequently are
      performed in the investigation of immunocompromised patients with lung disorders.
      The risk-benefit ratio of TBB currently is debated, since several authors have
      found that the less invasive BAL may provide as much information as TBB, with the
      avoidance of some biopsy-related side effects. We retrospectively evaluated 157
      instances of bronchoscopy carried out on 142 immunocompromised patients, with
      both BAL and TBB performed in every case. Immunosuppressant conditions were HIV
      infection (79), hematologic malignancies (36), and antirejection therapy in renal
      transplant recipients (27). Transbronchial biopsy provided a diagnostic yield
      significantly higher than that obtained by BAL in all categories investigated;
      diagnostic rates were 77.3% for TBB and 47.6% for BAL (p < 0.001) in patients
      with HIV infection, 55 and 20% (p < 0.001) in patients with hematologic
      malignancies, and 57.5 and 27.2% (p < 0.001) in renal transplant recipients.
      Looking at the whole series, the diagnostic rates of TBB and BAL were 67.5 and
      36.3%, respectively (p < 0.001), with a total additional yield of 33% provided by
      TBB, while in only 2% of cases BAL gave rise to diagnostic information not
      achieved by TBB. Considering that side effects followed TBB at a negligible rate
      (2.5%), we believe that TBB should be routinely carried out in these patients
      once the diagnostic strategy has been oriented to bronchoscopy.

PMID- 7813259
TI  - Evaluation of a prognostic score. Pneumocystis carinii pneumonia in HIV-infected
      patients.
AB  - STUDY OBJECTIVE: (1) To evaluate a clinical score predicting the early death from
      Pneumocystis carinii pneumonia (PCP) in HIV-infected patients and to compare it
      with lactate dehydrogenase (LDH) levels and Karnofsky's performance score. (2) To
      compare the association of this score and partial oxygen pressure (PaO2) at
      baseline (at ambiant air) with change in therapy. DESIGN: This clinical score was
      based on respiratory rate, degree of fever, cough, dyspnea, chest tightness, and
      chest radiographic findings. It was prospectively assessed in patients enrolled
      in two clinical trials for primary therapy of PCP. SETTING: A university hospital
      with a large AIDS population. PATIENTS: PCP scores (PCPSc) were assessed on
      treatment days (D) 0, D3, D7, D14, and D21 for 78 patients with mild to
      moderately severe PCP (PaO2 > 50 mm Hg at entry at room air). Regardless of the
      treatment received, these patients were stratified into two groups (survivors and
      nonsurvivors) within 45 days after the beginning of therapy. MEASUREMENTS AND
      RESULTS: The PCPSc was associated with 45 days survival at treatment D3 (p =
      0.03) and D14 (p < 0.001). Its decrease was significant between D0 and D7 and
      between D7 and D14 for survivors only. The LDH levels during the treatment course
      did not correlate with outcome. The fall in LDH values was significant only for
      survivors between D7 and D14 of therapy. The PaO2 at hospital admission was
      associated with death at 45 days and was well correlated with the PCPSc on D0 by
      single and multiple linear regression (R = 0.60, p < 0.0001). The PCPsc on D0 was
      associated with the change of initial therapy due to failure or drug adverse
      effects whereas PaO2 on D0 was associated only with treatment failure.
      CONCLUSIONS: For HIV-infected patients with mild to moderately severe PCP, this
      clinical score is easy to assess and has a prognostic value for survivors. It
      could be helpful to predict both treatment failure and occurrence of severe
      adverse drug reactions. The PCPSc should be validated in a larger number of
      patients, including those with more severe forms of PCP.

PMID- 7813260
TI  - Radiation exposure in standard and high-resolution chest CT scans.
AB  - It has been suggested that radiation doses due to high-resolution computed
      tomography (HRCT) of the chest are considerably higher than those from
      conventional CT. We compared the effective dose (E, mSv) in conventional chest CT
      (10-mm contiguous slices) and HRCT (1.5-mm slices, gap 10 mm). In our study, the
      effective dose from a HRCT (0.98 mSv) is about 6.5 times less than the effective
      dose from a standard CT scan (6.5 mSv), and only a factor 12 higher than from a
      conventional chest examination (0.085 mSv).

PMID- 7813261
TI  - Interobserver variation in the computed tomographic evaluation of mediastinal
      lymph node size in patients with potentially resectable lung cancer. Canadian
      Lung Oncology Group.
AB  - OBJECTIVE: To measure the reliability of the assessment of mediastinal lymph node
      size in computed tomographic (CT) scans of the thorax. DESIGN: Observer agreement
      study in which radiologists, blinded to one anothers' interpretation, were
      randomized to read 30 scans each. POPULATION: Sixty scans from patients with
      apparently operable non-small cell carcinoma of the lung were read by
      radiologists responsible for clinical interpretation (clinical radiologists) and
      four radiologists with a special interest in thoracic CT (study radiologists).
      MEASUREMENTS: Radiologists measured the size of left and right superior
      mediastinal nodes, aortic nodes, and the subcarinal nodes and, on the basis of
      whether any nodes accessible to mediastinoscopy were greater than 1 cm,
      recommended whether mediastinoscopy be undertaken. Agreement was quantified using
      kappa, a measure of chance-corrected agreement. RESULTS: Among all radiologists,
      agreement on whether there were any nodes larger than 1 cm for right superior
      mediastinal nodes was 0.68; for left superior mediastinal nodes it was 0.28; for
      aortic pulmonary nodes it was 0.62; for subcarinal nodes it was 0.58; and for any
      node greater than 1 cm and accessible to mediastinoscopy it was 0.61. The
      agreement was very similar when the analysis was restricted to the study
      radiologists. CONCLUSION: Although the good level of overall agreement suggests
      that CT provides useful information in the evaluation of mediastinal lymph node
      size, the disagreement was sufficient that it likely contributes to suboptimal
      sensitivity and specificity of CT in detecting tumor spread reported in previous
      studies.

PMID- 7813262
TI  - Reversible airway lesions in diffuse panbronchiolitis. Detection by high
      resolution computed tomography.
AB  - The clinical effectiveness of erythromycin for patients with diffuse
      panbronchiolitis (DPB) was previously recognized. However, it remains unknown
      what kind of airway lesions change with the clinical effectiveness induced by
      erythromycin. We performed the present study to clarify this unknown. We devised
      a method for scoring findings on high-resolution computed tomography (HRCT) to
      aid in the objective evaluation of the airway lesions in patients with DPB. The
      18 patients with DPB were treated with oral erythromycin, 600 mg/d. All patients
      were evaluated by pulmonary function tests and HRCT before and after 3 months of
      therapy. Characteristic HRCT findings in patients with DPB pretherapy were small
      nodules, airway ectasia, periairway thickening, and mucus plugging. After
      erythromycin therapy, there was significant reduction in scores for the extent of
      small nodular opacities, the severity of periairway thickening, and the extent of
      mucus plugging with a corresponding significant improvement in results of the
      pulmonary function test parameters. The present study demonstrated reversible
      airway lesions in patients with DPB in response to erythromycin therapy.

PMID- 7813263
TI  - Prevalence of radiographic small lung opacities and pleural abnormalities in a
      representative adult population sample.
AB  - The prevalence of radiographic widespread small lung opacities and pleural
      abnormalities in the general population was assessed as part of the Mini-Finland
      Health Survey, which was based on a representative sample of people aged 30 years
      or over. Full-size chest radiographs of 7,095 persons (89% of the sample) were
      classified. Two radiologists classified all the radiographs according to the ILO
      1980 Classification of Radiographs of Pneumoconioses. Small lung opacities and
      pleural abnormalities were considerably more prevalent in the older age groups
      and in men. Small lung opacities on the radiographs and pleural abnormalities
      were associated with work in industrial occupations, particularly in men. There
      was a clear association between small lung opacities and pleural abnormalities.
      The sex differences may be related to occupational factors, particularly dust
      exposure. The elevated risk of pleural plaques in persons with small lung
      opacities on the radiographs may indicate a fiber effect.

PMID- 7813264
TI  - High-resolution computed tomographic findings associated with histologically
      diagnosed acute lung rejection in heart-lung transplant recipients.
AB  - A group of 32 lung (single lung, [n = 14] and double lung [n = 1]) or heart-lung
      (n = 17) transplant recipients were studied with serial high-resolution computed
      tomography (HRCT) scans and transbronchial biopsies from the time of surgery.
      These investigations were carried out routinely every 2 weeks for the first 2
      months, every 2 months for a year, every 4 months in the second year, and on any
      clinical suspicion of acute lung rejection or infection. A total of 190
      transbronchial biopsy specimens and concurrent HRCT scans were obtained. Forty
      (21%) of the biopsy specimens, showed histologic evidence of lung rejection, 111
      (58%) were normal, and 39 (21%) were not conclusive. The more frequent HRCT
      pattern encountered during an acute rejection episode was the presence of patchy
      "ground-glass" density areas (65%). This finding was sparsely observed during
      minimal and mild acute rejection episodes. Using histologic diagnosis as a
      standard for acute rejection, ground-glass opacities on HRCT had a sensitivity of
      65% in detecting lung rejection. Although ground-glass opacities were also
      intermittently observed during cytomegalovirus pneumonia (14%), this finding had
      a specificity of 85% for detecting occurrence of an acute lung complication. The
      detection of ground-glass opacities on lung HRCT after lung transplantation, more
      particularly after the first month after surgery, can aid the decision of when
      and where to undertake transbronchial lung biopsy.

PMID- 7813265
TI  - Relationship between hemodynamics and right ventricular function in patients with
      cardiomyopathy. Important role of tricuspid regurgitation.
AB  - STUDY OBJECTIVE: Right ventricular (RV) ejection fraction is load sensitive,
      varying inversely with pulmonary artery pressure. We tested whether this
      relationship exists in dilated cardiomyopathy. DESIGN: Retrospective chart
      review. SETTING: Tertiary care referral medical center. PATIENTS: In 25 patients
      with cardiomyopathy referred for heart transplant evaluation (left ventricular
      ejection fraction 27 +/- 12%), hemodynamics, radionuclide angiograms, and Doppler
      echocardiograms were obtained initially (study A) and 8 +/- 8 months later (study
      B). RESULTS: Right ventricular ejection fraction was 40 +/- 17% on study A and 41
      +/- 16% on study B, with a wide range of change between studies (+38 to -28%).
      Pulmonary artery systolic pressure (PASP) and right atrial pressure increased (52
      +/- 9 to 61 +/- 10 mm Hg and 10 +/- 4 to 14 +/- 4 mm Hg, respectively, p < 0.05).
      There was no relation between PASP and RV ejection fraction (n = 50, r = -0.02, p
      = 0.87). Also, there was no relation between changes in PASP and RV ejection
      fraction (n = 25, r = 0.25, p = 0.15) between study A and B. However, there was a
      significant relation between interstudy changes in PASP and RV ejection fraction
      (n = 14, r = -0.71, p = 0.005) and end-systolic volume (n = 14, r = 0.53, p <
      0.05) in patients in whom the degree of tricuspid regurgitation was either none
      or mild on both study A and B. CONCLUSIONS: In patients with cardiomyopathy, RV
      ejection fraction cannot be used as a noninvasive marker of pulmonary
      hypertension. Owing to variation in tricuspid regurgitation, alterations in
      pulmonary artery pressure over time may not lead to the expected change in RV
      ejection fraction or end-systolic volume.

PMID- 7813266
TI  - Cardiopulmonary exercise testing following allogeneic lung transplantation for
      different underlying disease states.
AB  - OBJECTIVES: To assess the exercise response to single lung transplantation in
      chronic airflow obstruction (CAO), idiopathic pulmonary fibrosis (IPF), and
      pulmonary vascular disease (PVD) vs double lung transplantation at well-defined
      time points after transplantation, and to define the change in exercise response
      in SLT and DLT over the first year after transplantation. DESIGN: Prospective
      study. SETTING: Tertiary referral hospital. PATIENTS: Fourteen stable SLT
      recipients (6 with CAO, 4 with IPF, 4 with PVD) and 11 stable DLT recipients.
      MEASUREMENTS: Spirometry, lung volumes, diffusion lung capacity for carbon
      monoxide (DLco) and MVV measured prior to exercise at 3 months (n = 25) then at 3
      month intervals up to a maximum of 12 months post-transplantation (n = 18 [12 SLT
      and 6 DLT]). Symptom-limited cardiopulmonary exercise tests at same time points
      (n = 25 at 3 months, n = 18 [12 SLT and 6 DLT] at 3-month intervals up to 12
      months). Breathlessness was estimated by visual analogue scale prior to exercise
      and at peak exercise. RESULTS: At 3 months, FEV1 percent predicted was lower for
      SLT-CAO and SLT-IPF vs DLT (p < or = 0.05). Mean FEV1/FVC was lower for SLT-CAO
      vs all other groups (p < or = 0.05). The FVC, MVV, and DLco/VA were similar for
      all groups. The TLC and RV were higher for the SLT-CAO group compared with all
      others. The TLC was lower for SLT-PVD compared with DLT. Exercise responses were
      similar in all groups studied without a statistically significant difference in
      achieved VO2, work rate, O2 pulse, anaerobic threshold, heart rate response,
      respiratory rate, VE/MVV, and VT/VC. The change in O2 saturation during exercise
      was the least in recipients of DLT. Maximal achieved VO2 rose from 3 to 6 months
      after SLT but dropped by 9 to 12 months after transplantation. Maximal achieved
      VO2 trended up from 3 to 6 months after DLT but dropped by 9 to 12 months after
      transplantation. Maximal achieved work rate rose in both SLT and DLT from 3 to 9
      to 12 months after transplantation. There was no significant difference in
      breathlessness at rest and peak exercise measured between recipients of SLT or
      DLT. CONCLUSIONS: Minor differences in pulmonary function and change in O2
      saturation occur between recipients of SLT and DLT during the first
      posttransplant year. These differences are most pronounced when comparing SLT-CAO
      with DLT. However, there is no significant difference in exercise capacity
      between SLT for CAO, IPF, PVD, and DLT. The rise in maximum achieved VO2 over the
      first 6 months after transplantation may reflect the effects of exercise training
      and should be taken into account when examining aerobic response after
      transplantation.

PMID- 7813267
TI  - Effect of hypoxic sensitivity on decay of respiratory short-term potentiation.
AB  - In normal conscious humans, when a brief hypoxic ventilatory stimulus is followed
      immediately by breathing 100% O2, ventilation during hyperoxia gradually declines
      to baseline prehypoxic levels without an undershoot. During the decline,
      ventilation is greater than baseline in the absence of hypoxia and hypercapnia.
      This has been interpreted as evidence of decay of short-term potentiation (STP)
      or afterdischarge. It is not known whether the intensity of the stimulus that
      activates STP influences the time course of its decay. Therefore we studied STP
      decay in nine normal adults after administration of placebo (P) and almitrine (A)
      in a single-blind manner on 2 separate days. On each day, three runs consisting
      of 45 s of isocapnic hypoxia (end-tidal PO2 = 55 mm Hg) followed by 2 min of
      hyperoxia were conducted while ventilation (VI) was measured breath by breath.
      Baseline VT did not differ between A and P, but at the end of hypoxia, VI with A
      was 169 +/- 14% (SE) of baseline while VI with P was 132 +/- 7% of baseline (p <
      0.05). Immediately after hyperoxia was instituted, VI fell abruptly, the fall
      being 36% of baseline for A and 15% for P. This probably represented the
      withdrawal of peripheral chemoreceptor input. Thereafter, VI declined slowly
      toward baseline, and the time course of this decline did not differ between P and
      A. Our results indicate that within the limits we studied, the increase of the
      intensity of the discharge of the peripheral chemoreceptors during hypoxia does
      not influence STP decay.

PMID- 7813268
TI  - Intraindividual peak flow variability.
AB  - OBJECTIVES: To quantify intraindividual variability in peak expiratory flow (PEF)
      measured with peak flow-meters and to define factors affecting PEF variability.
      METHODS: Three hundred one healthy subjects (aged 4 to 84 years) were recruited
      from sites at sea level (n = 220) and at 1,400 m altitude (n = 81). All testing
      was done with the same model peak flowmeter. Each subject was actively coached
      through five to eight successive PEF maneuvers. Three meters of the same model
      were tested using a mechanical waveform simulator at three different flows at
      both testing altitudes (sea level and at 1,400 m). RESULTS: Excluding outliers,
      the mean PEF was 523 L/min, mean standard deviation (SD) was 22 L/min, and mean
      coefficient of variation (CV) was 4.6%. The upper 95th percentile for CV was 8%
      for adults and 10% for youths. Analyzing only the three highest peak flows for
      each subject, the mean PEF was 539 L/min, mean SD was 12 L/min, and mean CV was
      2.4%. The upper 95th percentile for CV was 6% for adults and 9% for youths.
      Linear regression analysis revealed a small but statistically significant
      correlation (p < 0.01) between mean peak flow and CV. In adults, SD correlated
      with sex (p < 0.01) but neither CV nor SD was correlated with age, height,
      weight, or altitude. Meter variability defined with the mechanical waveform
      simulator was small. Standard deviation varied from 1.5 to 4.2 L/min and CV from
      0.4 to 1.6%. When the three largest peak flows for each subject were used, 5.5%
      of intraindividual variance was explained by meter variance. CONCLUSIONS: These
      estimates of intraindividual variability in healthy subjects are generally lower
      than those previously reported. Meter variability accounts for only a small part
      of total intraindividual variability. The 95th percentile data suggest that a
      fall in PEF of 6 to 8% in adults and 9 to 10% in youths would be statistically
      significant.

PMID- 7813269
TI  - Left ventricular dysfunction in deteriorating patients with chronic obstructive
      pulmonary disease.
AB  - OBJECTIVE: To evaluate the effectiveness of simple clinical variables and
      radionuclide ventriculogram in separating those patients with isolated chronic
      obstructive pulmonary disease (COPD) from those with COPD and coexisting left
      ventricular dysfunction (LVD). DESIGN: Retrospective record review of 77 patients
      with increasing dyspnea, defined as recent deterioration in exercise tolerance,
      new use of corticosteroids, or recent hospital admission for COPD; referred to
      the outpatient Pulmonary Rehabilitation Program at the Cincinnati Veterans
      Affairs Medical Center from July 1987 to October 1992. SETTING: Outpatient
      medical clinic. PATIENTS: Veterans who were referred to the Pulmonary
      Rehabilitation Program. MEASUREMENTS: History and physical findings, pulmonary
      function tests, arterial blood gases, distance achieved in a 12-min walk, dyspnea
      score, electrocardiogram, chest radiograph, and radionuclide multigated
      ventriculography. RESULTS: Twenty-five of 77 patients evaluated in the Pulmonary
      Rehabilitation Program for increasing dyspnea were functionally more limited (12
      min walk 10.4 vs 13.9 laps; MRC score 2.68 vs 2.06; p < 0.05) and had left
      ventricular dysfunction (LVD) (left ventricular ejection fraction < 40%)
      associated with wall motion abnormalities on radionuclide ventriculogram. Careful
      standard clinical evaluation did not separate those patients with COPD from those
      with both COPD and LVD. CONCLUSIONS: LVD was found in 32% of patients with COPD
      presenting with symptomatic deterioration. Since the therapeutic approach to
      these two disorders differs, the identification of patients with LVD is
      important. Prospective studies are needed to identify the most cost-effective
      approach to this problem of coexisting disease and to evaluate the benefit from
      therapy.

PMID- 7813270
TI  - Effect of inhaled norepinephrine on the nitroglycerin-induced bronchodilatation
      in asthmatics.
AB  - Previous studies on the bronchodilating effect of nitrates yielded conflicting
      results. We hypothesized that the concomitant bronchial vasodilatation induced by
      nitrates may limit the increase of airway patency due to bronchial smooth muscle
      relaxation. To test this hypothesis, we evaluated the bronchodilating effect of
      nebulized nitroglycerine (NTG), 0.2 mg, in 12 patients with reversible airway
      obstruction (FEV1 64.3 +/- 8.2% predicted, > 15% increase after salbutamol 200
      micrograms by metered-dose inhaler), pretreated with aerosolized norepinephrine
      (NE) (0.04 mg) or placebo (PL), in a randomized double-blind crossover design, in
      two separate days. Baseline FEV1 values of the two test days and FEV1 after NE or
      PL inhalations were not significantly different. After NTG inhalation, FEV1 was
      73.8 +/- 7.9% predicted, with NE pretreatment, and 70 +/- 8.2% predicted with PL
      pretreatment (p < 0.01). The maximal percent increases of FEV1 above baseline
      were 14.9 +/- 4.8% and 9.2 +/- 2.4%, respectively, after NE and PL pretreatment
      (p < 0.01). In conclusion, NTG produces a better bronchodilatation when the
      concomitant vasodilatation is attenuated by a vasocostrictive agent.

PMID- 7813271
TI  - Nonbronchodilator effects of pirbuterol and ipratropium in chronic obstructive
      pulmonary disease.
AB  - BACKGROUND: Although both beta-adrenergic agonists and anticholinergic agents are
      widely used in the treatment of patients with COPD, they influence the pulmonary
      circulation and ventilation differently. We compared the effects of these two
      agents on gas exchange and distribution of ventilation in COPD. METHODS:
      Pirbuterol and ipratropium bromide were administered by inhalation via a metered
      dose inhaler to 12 and 14 patients with COPD, respectively, in a randomized,
      double-blind fashion. Pulmonary function tests, arterial blood gas levels, heart
      rate, resting minute ventilation (VE), physiologic dead space volume to total
      ventilation ratio (VD/Vt) and oxygen consumption (VO2) were measured prior to and
      then 5, 15, 30, and 60 min after administration of the respective drugs. The
      changes in these measurements after administration of the two drugs were analyzed
      and compared with each other. RESULTS: The pulmonary function test measurements
      showed similar improvement after administration of both drugs. Heart rate fell in
      both groups. After administration of pirbuterol, the alveolar-arterial oxygen
      pressure difference (P[A-a]O2) and VE rose significantly and the rise in FEV1
      showed a negative correlation with the fall in PaO2. In contrast, the use of
      ipratropium bromide did not produce these effects, but resulted in a fall in VO2
      and a rise in VD/Vt. CONCLUSION: Pirbuterol and ipratropium are equally effective
      bronchodilators in COPD. Pirbuterol results in a significant rise in P(A-a)O2 and
      resting VE. Ipratropium does not affect these measurements and seems to reduce
      the oxygen cost of breathing. The results suggest significant differences between
      the effects of the two agents on gas exchange, ventilation, and VO2 which could
      be of clinical significance.

PMID- 7813272
TI  - Small cell carcinoma of the esophagus. The Massachusetts General Hospital
      experience, 1978 to 1993.
AB  - Thirteen patients with small cell carcinoma of the esophagus were treated at the
      Massachusetts General Hospital between 1978 and 1993. These patients accounted
      for 1.6% of all patients with esophageal neoplasms seen at our institution during
      this period. Five patients presented with extensive disease while eight were
      noted to have limited disease at diagnosis. Seven patients were treated with
      primary chemotherapy while four patients received radiation therapy alone. No
      patient in this series underwent surgical resection. Four complete responses to
      treatment were observed although overall survival was only 7 months. One patient
      receiving chemotherapy, external beam radiation therapy, and endoesophageal
      brachytherapy is alive and well without evidence of disease 24 months from
      diagnosis.

PMID- 7813273
TI  - Antegrade cannulation of radial artery in infants and children.
AB  - We describe the novel approach of antegrade radial artery cannulation in five
      pediatric patients after failure of standard retrograde cannulation by
      percutaneous and cutdown technique. This antegrade cannulation led to successful,
      reliable continuous blood pressure monitoring and arterial blood sampling without
      complications. We believe antegrade cannulation can be successfully used when
      radial arteries are obstructed and retrograde blood flow is observed during
      failed cutdown attempts at standard retrograde arterial cannulation.

PMID- 7813274
TI  - Aspiration complicating bronchopulmonary dysplasia.
AB  - The purpose of this study was to study the relationship of aspiration with
      ongoing respiratory difficulties in infants with bronchopulmonary dysplasia
      (BPD). Twelve infants with BPD were identified out of 314 children who had
      flexible bronchoscopy between 1987 and 1990; 11 of 12 had bronchoalveolar lavage
      (BAL). The lipid index (LI) was used to quantify the degree of lipid-laden
      macrophages in the BAL fluid as a marker of aspiration. The age range at the time
      of bronchoscopy was 3 months to 5 years. The LI was considered positive in 6 of
      11 subjects. A pH probe study was done on seven subjects with concordant findings
      in five. Other findings included dynamic or structural airway abnormalities in 10
      of the 12 subjects. These data suggest that aspiration frequently is associated
      with BPD in addition to the previously recognized dynamic and structural airway
      problems. The predisposition to gastroesophageal reflux and laryngeal injury
      probably accounts for the increased aspiration risk in children with BPD.

PMID- 7813275
TI  - Pulmonary tuberous sclerosis.
AB  - We describe the clinical presentation, pulmonary function tests, chest
      radiograph, and computed tomography findings, response to hormonal treatment, and
      duration of survival of nine patients with pulmonary involvement in tuberous
      sclerosis complex with follow-up over an average of 17 years (range, 1 to 35
      years) since diagnosis. All patients were female, and the average age at onset of
      symptoms was 16 years (range, 3 months to 39 years); pulmonary symptoms did not
      develop until an average age of 33 years (range, 22 to 46 years). There was an
      average delay of 8 years before the correct diagnosis was made. The most common
      presenting clinical features were seizures, pneumothorax, bleeding into a renal
      angiomyolipoma, dyspnea, and typical skin changes. Pulmonary function tests
      commonly demonstrated obstruction to airflow and reduced single-breath diffusing
      capacity. Chest radiograph and computed tomography characteristically
      demonstrated diffuse interstitial infiltrates with cystic changes. Two
      asymptomatic patients with mild pulmonary involvement have remained in stable
      condition without hormonal therapy. The remaining seven patients had moderate to
      severe airflow obstruction; of these, five underwent hormonal therapy. Three
      patients had a clinical response to treatment. Two patients who did not receive
      hormonal treatment died of progressive respiratory failure. Most patients with
      pulmonary involvement in tuberous sclerosis have a slowly declining clinical
      course. Although the available data are limited, they suggest that a trial of
      hormonal therapy is recommended both for symptomatic patients and for those with
      declining pulmonary function. Tuberous sclerosis complex should be suspected in
      all patients with the diagnosis of lymphangioleiomyomatosis.

PMID- 7813276
TI  - Pulmonary fibrosis correlates with outcome in adult respiratory distress
      syndrome. A study in mechanically ventilated patients.
AB  - STUDY OBJECTIVE: The present study was carried out to evaluate the prognostic
      value of pulmonary fibrosis diagnosed on the basis of pulmonary samples obtained
      by fiberscopic transbronchial lung biopsy (TBLB) in patients treated for severe
      established adult respiratory distress syndrome (ARDS). DESIGN: Prospective
      cohort study. SETTING: Intensive Care Unit of a University Hospital. PATIENTS:
      Consecutive patients with a diagnosis of established ARDS. INTERVENTIONS: Samples
      of pulmonary tissue (3 to 6 in each patient) were obtained by fiberoptic TBLB.
      Severity of pulmonary fibrosis was assessed based on pathologic changes.
      Hematoxylin and eosin and Masson's trichrome stains were performed on each tissue
      sample. MAIN RESULTS: Twenty-two lung specimens were obtained from 25 consecutive
      patients with ARDS of various origin (postsurgical complications, 7 patients;
      multiple trauma, 8 patients; medical problems, 7 patients). Transbronchial lung
      biopsy was complicated by small or moderate hemorrhage in three patients. No case
      of pneumothorax was identified. Pathologic findings showed that 14 patients (64%)
      had pulmonary fibrosis, either mild (9 patients) or moderate to severe fibrosis
      (5 patients). In the patients with pulmonary fibrosis, mortality rate was 57% (8
      out of 14 patients), which was significantly different (p < 0.02) from the 0%
      mortality rate observed in patients without pulmonary fibrosis. Severity of
      pulmonary fibrosis (mild vs moderate and severe) did not influence outcome. With
      the exception of pathologic findings, characteristics of patients with and
      without pulmonary fibrosis (PaO2, PaCO2, the ratio of PaO2 to fraction of
      inspired oxygen, and positive end-expiratory pressure) were not different.
      CONCLUSION: In the study patients, pulmonary fibrosis diagnosed on the basis of
      TBLB was closely related to fatality in established ARDS.

PMID- 7813277
TI  - Long-term survival of patients with coronary artery disease during the 1970s. A
      cohort study.
AB  - STUDY OBJECTIVE: This study was undertaken to determine the effects of altered
      risk factors and treatment modalities on the short- and long-term survival of
      patients with documented coronary artery disease whose conditions were diagnosed
      from 1972 through 1982. STUDY DESIGN: The study was a retrospective database
      analysis of clinical, angiographic, and follow-up information. SETTING: Data from
      all patients referred for cardiac catheterization at the Baptist Memorial
      Hospital, Memphis, Tenn, were studied. PATIENTS: Risk factors and survival of
      patients who underwent cardiac catheterization from 1972 through 1982 and who
      were followed up for at least 5 years were evaluated. Cohort A included 1,821
      patients studied from 1972 through 1977; cohort B included 5,369 patients studied
      between 1977 and the end of 1982. Each cohort was subdivided based on type of
      therapy (medical or surgical) that the patients received. MEASUREMENTS AND
      RESULTS: The 30-day (short-term) and 5-year (long-term) survival rates were
      compared by life table methods. Short-term survival improved significantly in
      both medical (from 94.9% to 97.5%, p < 0.001) and surgical (from 95.5% to 97.6%,
      p < 0.001) groups from cohort A to cohort B. Long-term survival, however, did not
      differ significantly between the two cohorts. In the medical group, 5-year
      survival in cohort A was 86.3% and in cohort B it was 86.9% (p = NS); in the
      surgical group, cohort A it was 89.1% while in cohort B it was 89.4% (p = NS).
      Prevalence of both cigarette smoking and hypercholesterolemia declined
      significantly from cohort A to cohort B in both surgical and medical groups.
      However, advanced age, female gender, and previous myocardial infarction were
      significantly more common in cohort B than in cohort A for both treatment groups.
      CONCLUSIONS: These results indicate that during the study period, a significant
      decline in short-term mortality occurred for patients with angiographically
      documented coronary artery disease. Long-term survival did not, however, improve
      possibly due to a complex interplay between factors that promote coronary artery
      disease, eg, cigarette abuse and hypercholesterolemia, and factors that determine
      survival, eg, increase in age and history of prior infarction and advances in
      medical and surgical therapy.

PMID- 7813278
TI  - Reversal of 'refractory septic shock' by infusion of amrinone and angiotensin II
      in an anthracycline-treated patient.
AB  - A 53-year-old granulocytopenic woman with malignant lymphoma treated with
      cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy,
      including doxorubicin (Adriamycin) and autologues bone marrow transplantation,
      presented in the clinical state of "refractory septic shock" caused by
      Escherichia coli. Despite inotropic treatment with dopamine, dobutamine, and
      norepinephrine infusion, the patient's condition did not improve, but during
      treatment with amrinone and angiotensin II infusion, the septic shock was
      reversed. The patient was monitored with a pulmonary artery catheter and
      underwent repeated echocardiographic examinations. Antibiotic treatment with
      thienamycin and floxacillin was given. The initial reduction in cardiac
      performance in this patient may be explained by a state of true down-regulation
      of the myocardial beta-receptors. Apparently these beta-receptors were bypassed
      via the enzymatic action of amrinone upon cyclic monoadenosine phosphate. This
      is, to our knowledge, the first doxorubicin-treated patient with septic shock
      refractory to conventional vasopressor therapy whose condition reversed by
      inotropic treatment with amrinone and angiotensin II. This treatment may prove to
      be an alternative choice for patients developing "refractory septic shock"
      unresponsive to treatment with norepinephrine, dobutamine, and dopamine.

PMID- 7813279
TI  - Work of breathing after extubation.
AB  - Recently we showed that work of breathing was higher in the immediate period
      after extubation as compared with spontaneous breathing through an endotracheal
      tube. In this study, we evaluated the glottis and trachea as potential sites of
      increased airway resistance after extubation. We measured breathing pattern, work
      of breathing, and pressure time product in eight patients during weaning from
      mechanical ventilation. We acquired data during pressure support ventilation and
      spontaneous breathing via the ventilator, with the endotracheal tube in place,
      and after extubation. During bronchoscopy at the time of extubation, we examined
      the trachea and measured the cross-sectional area of the glottis. Work of
      breathing and pressure time product were significantly lower during pressure
      support ventilation as compared with spontaneous breathing after extubation (0.43
      +/- 0.10 vs 1.49 +/- 0.10 J/L and 101 +/- 22 vs 299 +/- 30 cm H2O.s/min,
      respectively; p < 0.05). However, both indexes were significantly higher after
      extubation as compared with breathing through the endotracheal tube (1.49 +/-
      0.10 vs 0.95 +/- 0.12 J/L, 299 +/- 31 vs 196 +/- 26 cm H2O.s/min respectively; p
      < 0.05). During bronchoscopy, no tracheal or glottic narrowing was detected. The
      glottic cross-sectional area was successfully measured in four patients at the
      onset of inspiration and found to be 140 +/- 15 mm2. This value was larger than
      the mean cross-sectional area of the endotracheal tubes used in these patients
      (50 mm2). We conclude that neither tracheal nor laryngeal disease caused the
      increase in work of breathing after extubation. Our data suggest that upper
      airway narrowing at a more proximal site, such as the oropharynx or velopharynx
      may be the cause of the increase in respiratory work.

PMID- 7813280
TI  - Treatment of bronchospasm by metered-dose inhaler albuterol in mechanically
      ventilated patients.
AB  - beta 2-agonist bronchodilators delivered by metered-dose inhalers (MDI) are
      commonly used in the treatment of bronchospasm in both intubated and nonintubated
      patients. Substantial data support the effectiveness of MDI delivery systems in
      nonintubated patients. However, few studies have examined the effectiveness of
      MDIs in intubated, mechanically ventilated patients. MDIs are often used in
      conjunction with a spacing device that may enhance delivery of drug to the
      airways, but few in vivo data have demonstrated efficacy of this delivery method
      in ventilated patients. We studied ten critically ill patients who had a peak
      (Ppeak) to pause (Ppause) gradient of more than 15 cm H2O during sedated, quiet
      breathing on assist control ventilation. We administered 5, 10, and 15 puffs (90
      micrograms per puff) of MDI albuterol through a specific spacer (Aerovent) at 30
      min intervals, while measuring resistive pressure (defined as Ppeak-Ppause)
      before and after treatments. Resistive airway pressure after 5 puffs decreased in
      nine of ten patients, from 25.1 +/- 7.2 to 20.8 +/- 5.6 cm H2O (p < 0.12). The
      addition of 10 more puffs further reduced resistive pressure in nine of nine
      patients from 20.8 +/- 5.6 to 19.0 +/- 4.4 (p < 0.01). Fifteen more puffs (30
      cumulative puffs) did not result in further improvement (p > 0.5). A toxic
      reaction occurred in one patient (systolic blood pressure decreased 20 mm Hg)
      after 5 puffs of albuterol. We conclude that MDI administered through this
      specific spacer is effective in mechanically ventilated patients in doses up to
      15 puffs, and that therapy should be titrated to effectiveness and toxicity.

PMID- 7813281
TI  - Rapidly fatal outcome of bacteremic Klebsiella pneumoniae pneumonia in
      alcoholics.
AB  - Twenty-eight alcoholic patients with community-acquired pneumonia who were
      admitted to a referral medical center during a 3-year period were reviewed. All
      were men and with few exceptions were heavy smokers. The overall mortality was
      64.3%. The most dramatic group was that of 11 patients (39.3%) with bacteremic
      Klebsiella pneumoniae pneumonia (BKPP), which had high mortality rate (100%),
      short onset of illness before hospital admission (42.6 +/- 8.2 h, mean +/- SD),
      and short survival time after the admission (24.6 +/- 7.9 h). All these 11
      patients needed intensive care unit (ICU) management and ventilatory support.
      ARterial blood gas values showed marked hypoxemia and metabolic acidosis in most
      of these 11 patients, and presence of shock at arrival in the hospital was noted
      in 8 patients. Acute renal failure and disseminated intravascular coagulation
      developed in six patients. Chest radiographs showed pleural effusion and
      radiographic spread in nearly 50% of patients. Combination chemotherapy
      consisting of one aminoglycoside and one second- or third-generation
      cephalosporin was initiated in all patients. The rapidly fatal outcome of these
      11 patients with BKPP despite management with adequate antibiotics and intensive
      care indicated the fulminant nature of this disease. High virulence of the
      microorganism, altered immune response, and increased susceptibility to infection
      may all have contributed to the fulminancy in this group of patients. The disease
      continues to present many difficulties in management.

PMID- 7813282
TI  - Hemodynamic correlates of outcome in patients undergoing orthotopic liver
      transplantation. Evidence for early postoperative myocardial depression.
AB  - OBJECTIVE: To describe the hemodynamic and oxygen transport patterns in survivors
      and nonsurvivors following liver transplantation (LT) and to assess their
      relationship to organ failure and mortality. DESIGN: Retrospective cohort.
      SETTING: Surgical ICU in a tertiary care university teaching hospital. PATIENTS:
      Consecutive series of 113 adults undergoing LT between 1984 and 1992. Patients
      were excluded if they died intraoperatively (n = 2), required retransplantation
      (n = 8), or their records were incomplete (n = 7). MEASUREMENTS AND MAIN RESULTS:
      Preoperative severity of illness was assessed by the acute physiology and chronic
      health evaluation (APACHE) II scoring system. Hemodynamic and oxygen transport
      variables were recorded immediately preoperatively and sequentially every 12 h
      during the first 2 postoperative days. Organ failures (pulmonary, renal,
      cardiovascular, hepatic, and central nervous system) were assessed for patients
      in the postoperative period. Patients were grouped as survivors (n = 82) or
      nonsurvivors (n = 14) with a mortality rate of 15%. Preoperative APACHE II scores
      were significantly lower in survivors compared with nonsurvivors (7 +/- 0 vs 11
      +/- 2; p = 0.029). Both preoperatively and postoperatively, survivors sustained a
      relatively higher mean arterial pressure, stroke volume index, left ventricular
      stroke work index, cardiac index, and oxygen delivery as compared with
      nonsurvivors (p < 0.01). The postoperative decline in systemic blood flow that
      was seen in both groups was particularly prominent in nonsurvivors during the
      first 12 h following LT (p < 0.03). Nonsurvivors sustained an approximately
      fivefold increase in the rate of organ failure (p < 0.0001); all patients (n = 6)
      with 4 or more organ failures died. CONCLUSION: Nonsurvivors of LT have less
      cardiac reserve pretransplant; postoperatively, they demonstrate early myocardial
      depression and subsequently lower levels of cardiac index and oxygen delivery.
      Patients who develop these hemodynamic patterns are more prone to organ failure
      and death.

PMID- 7813283
TI  - Current status of thrombolysis in acute myocardial infarction. I. Optimal
      selection and delivery of a thrombolytic drug.

PMID- 7813284
TI  - The pulmonary complications of crack cocaine. A comprehensive review.

PMID- 7813285
TI  - Current concepts in transcription, translation, and the regulation of gene
      expression. A primer for the clinician.

PMID- 7813286
TI  - Continuous negative extrathoracic pressure and positive end-expiratory pressure.
      A comparative study in Escherichia coli endotoxin-treated neonatal piglets.
AB  - Recent clinical studies have suggested that improvement in pulmonary gas exchange
      with the use of continuous negative extrathoracic pressure (CNEP) in conjunction
      with intermittent mandatory ventilation (IMV) may be due to increased pulmonary
      blood flow. Accordingly, we investigated the effects of CNEP vs positive end
      expiratory pressure (PEEP) in ventilated neonatal piglets after Escherichia coli
      endotoxin was administered to induce pulmonary hypertension. Two experimental
      groups of piglets with six in each, were subjected to three 30-min alternating
      periods--6 cm H2O CNEP with 6 cm H2O PEEP, beginning 2 h after endotoxin
      infusion. End-expiratory lung volume (EELV) increased similarly from baseline (13
      +/- 2 mL/kg) with both CNEP (28 +/- 2 mL/kg) and PEEP (29 +/- 2 mL/kg). In
      addition, the increase in PaO2 from baseline with CNEP (106 +/- 9 to 135 +/- 7 mm
      Hg) was similar to that with PEEP (114 +/- 11 to 132 +/- 6 mm Hg). Further, no
      differences were found in dynamic lung compliance, EELV, lung resistance, blood
      gas indexes, or hemodynamics, including transmural pulmonary artery pressure and
      pulmonary vascular resistance between CNEP and PEEP. With transpulmonary pressure
      and transrespiratory pressure equal, CNEP in tandem with IMV is physiologically
      equivalent to PEEP and IMV.

PMID- 7813287
TI  - Independent lung ventilation with a single ventilator using a variable resistance
      valve.
AB  - Independent lung ventilation using two ventilators has been attempted in the
      treatment of acute respiratory failure due to unilateral lung disease. However,
      this method has been found to be cumbersome and difficult to use. We reasoned
      that a bifurcated endotracheal tube with a variable resistance valve may enable
      us to change the inspiratory airway pressures and, hence, the inspired tidal
      volume to one lung using a single ventilator. We tested this hypothesis in eight
      anesthetized sheep and created a bronchopleural fistula in one lung as a model of
      unilateral lung disease. A bifurcated endotracheal tube was placed to separate
      the ventilation to each lung and, through a "Y" connector, both right and left
      lungs were ventilated simultaneously with a single ventilator. A variable
      resistance valve was placed between the "Y" connector and the tube ventilating
      the experimental lung with bronchopleural fistula. With a ventilator-generated
      peak inspiratory pressure of 31 +/- 2 cm H2O, the airway pressure distal to the
      valve was randomly changed from 31 cm H2O to 23 +/- 2, 15 +/- 1, 8 +/- 1, and 0
      cm H2O. This resulted in progressive diversion of tidal volume from the
      experimental lung to the control lung and an increase in exhaled tidal volume due
      to a decrease in air leak from the bronchopleural fistula. These data suggest
      that a variable resistance valve may be used for independent lung ventilation
      using a single ventilator.

PMID- 7813288
TI  - Airway mucus and epithelial function in a canine model of single lung
      autotransplantation.
AB  - Impaired mucociliary function following lung transplantation has been reported in
      several human and animal studies. This could be a result of altered ciliary
      function or mucus properties or both. We assessed airway epithelial function by
      means of transepithelial potential difference (PD) measurements and physical
      analysis of mucus. Six mongrel dogs underwent single lung autologous
      transplantation. Measurements were performed preoperatively and 1, 2, 4, and 10
      months postoperatively. At 1 and 2 months postoperatively, there was a
      significant fall in PD for the transplanted, left mainstem bronchus only (-13.5
      +/- 1.7 mV at 1 month and -14.6 +/- 1.7 mV at 2 months postoperatively vs -18.6
      +/- 2.3 mV preoperatively, baseline; p < 0.001 for both). The PD values in the
      small airways, right mainstem bronchus, and the trachea remained unchanged. At 2
      months postoperation, the mucus collection rate on the left side was increased (p
      = 0.03), while the mucus viscoelasticity was decreased (p = 0.04). By 4 months
      postoperation, all epithelial parameters had returned to baseline, and there was
      no difference in radioaerosol clearance between the two lungs. The PD decrease
      and alterations in secretion rate and viscoelasticity reflect disturbed
      epithelial functional integrity at the site of anastomosis still present at 2
      months postoperation. Recovery of bronchial epithelial function and clearance in
      canine studies of lung autotransplantation after healing of the anastomosis area
      suggest that persistent impairment of lung clearance observed in some long-term
      human lung transplantation survivors may be due to other mechanisms such as
      impaired healing or epithelial function or both, during immunosuppressive
      therapy. Mucociliary function in the anastomosis area is compromised until
      complete healing ensues; we speculate that chest physiotherapy may aid in
      overcoming this obstacle.

PMID- 7813290
TI  - Dyspnea, nonproductive cough, and blasts on the peripheral smear.

PMID- 7813289
TI  - Application of thoracoscopy for lung metastases.
AB  - Lung nodules in patients with a history of malignancy usually require tissue
      diagnosis that will provide prognostic information and dictate further therapy.
      Patients with a favorable tumor histologic condition and limited tumor burden
      were often considered for resection. This is usually accomplished by wedge
      resection through open thoracotomy when the lesions were peripheral. However,
      complications related to open thoracotomy often exclude poor-risk patients,
      especially those with impaired pulmonary function. Currently, technique of
      thoracoscopic resection is opening up new vistas and unimagined options for the
      thoracic surgeon in the management of pulmonary diseases. With the application of
      thoracoscopy and small incisions, it is now possible for the thoracic cavity and
      its contained organs to be thoroughly explored. Our recent experience with the
      thoracoscopic resection as a primary treatment for lung metastases is the focus
      of this report. Forty-seven patients with a history of malignancy and new lung
      metastases underwent this type of resection. Postoperatively, there is less pain,
      quick functional recovery, and excellent cosmetic healing. It is a safe and
      promising approach.

PMID- 7813291
TI  - Solitary pulmonary nodule in a 62-year-old man.

PMID- 7813292
TI  - Localized right upper lobe edema.
AB  - One of the lesser known atypical forms of radiographic presentation of pulmonary
      edema is the isolated or predominant affection of the upper right lobe in
      patients with mitral valve insufficiency. As a possible cause of this
      distribution, it has been established that the regurgitation jet during the
      ventricular systole may be directed selectively toward the orifice of the right
      upper lobe vein, locally accentuating the forces responsible for edema formation.
      There are few cases with these characteristics in the literature reviewed. We
      present an additional three cases, concluding that localized pulmonary edema
      secondary to mitral insufficiency should be suspected in the presence of any type
      of airspace consolidation in the right upper lobe, with or without associated
      affection of the middle lobe, in patients with a history of mitral valve
      insufficiency, especially when there are radiologic signs of left heart failure.

PMID- 7813293
TI  - Single lung transplantation for pulmonary lymphangiomyomatosis. Unexpected need
      for extracorporeal circulation.
AB  - The present case describes an acute respiratory-related hemodynamic failure
      during a single left lung transplantation in a 32-year-old woman suffering from
      end-stage pulmonary lymphangiomyomatosis. During the first 5 min of single right
      lung ventilation, a progressive increase in airway pressure and decrease in tidal
      volume associated with a decrease in arterial pressure and Spo2 occurred that
      were successfully countered by reventilation of the left lung. Proper positioning
      of the double-lumen tube was confirmed with a fiberoptic bronchoscope. Despite
      deliberate hypoventilation, within a few respiratory cycles, each further attempt
      at single lung ventilation was followed by abrupt hypotension, increase in
      pulmonary artery pressure, while airway pressure rose and tidal volume collapsed.
      The surgical team saw no signs of right pneumothorax. In these circumstances,
      cardiopulmonary bypass was required to perform pneumonectomy and grafting.
      Postoperatively a right anterior pneumothorax remained undiscovered on standard
      radiograph but was later revealed on soft radiograph. This acute intraoperative
      respiratory failure could equally well have been related to air trapping, in
      which case, however, deliberate hypoventilation would have been effective. In
      addition, the striking difference between the progressive onset of the first
      episode of hemodynamic failure and the immediate onset of the others argues in
      favor of a pneumothorax being at cause. Patients with pulmonary
      lymphangiomyomatosis are at high risk for intraoperative pneumothorax, but in our
      case, it could not be confirmed and treated during the surgical procedure without
      putting the patient at high risk for lung injury because of pleurodesis due to
      earlier pleural abrasion. This case again clearly shows the need to have
      cardiopulmonary bypass whenever single lung transplantation is performed.

PMID- 7813294
TI  - Reduced vital capacity in elderly persons with hypertension, coronary heart
      disease, or left ventricular hypertrophy. The Cardiovascular Health Study.
AB  - The Cardiovascular Health Study provided the opportunity to determine the
      association of subclinical and clinical cardiovascular disease with pulmonary
      function in a population sample of elderly adults. Included were 2,955 women and
      2,246 men over age 64 years who were recruited for this observational study from
      four communities and completed extensive examinations that included spirometry,
      echocardiograms, and blood pressure. Current smokers, past smokers with >20 pack
      years of smoking, and persons with a history of asthma, chronic bronchitis, or
      emphysema were excluded from this analysis, leaving 2,784 (55%) of the cohort.
      Systolic hypertension or coronary artery disease was associated with 40- to 100
      mL decrements in FEV1, and 50- to 150-mL decrements in FVC, while a history of
      congestive heart failure was associated with 200 to 300 mL lower FEV1 and FVC
      values (p < 0.0001), after correcting for age, height, and waist size. Higher
      left ventricular (LV) mass was also significantly associated with a decrease in
      FEV1 and FVC in multivariate models. This relationship was strongest with the end
      diastolic LV posterior wall thickness component of LV mass. In summary, FEV1 and
      FVC are reduced in elderly persons with hypertension, ischemic heart disease,
      higher disease, higher LV mass, and congestive heart failure, though the
      magnitude of these associations is relatively small unless heart failure
      supervenes. Substantial decrements in percent predicted FEV1 and FVC should not
      be attributed to the presence of uncomplicated ischemic heart disease or
      hypertension alone.

PMID- 7813295
TI  - A deformation sequence of heart, chest wall, and skin.
AB  - A white male infant was born with dextrocardia and a depressed area on the left
      anterior chest wall. The depressed area moved paradoxically with respiration, and
      was covered by abraded skin. The left arm, when flexed, fit into this depression.
      It is hypothesized that this represents a new deformation sequence.

PMID- 7813296
TI  - Reversal of digital clubbing after lung transplantation.
AB  - Digital clubbing is a common sign in a variety of lung diseases. Although its
      pathogenesis remains unclear, it is known that the degree of clubbing might vary
      and even disappear, particularly when the underlying disease is a malignant
      neoplasm that has been removed. By contrast, because of the short expectancy of
      life in patients with pulmonary fibrosis, it is unusual to observe regression of
      clubbing. In this work, we report a case of reversible clubbing after lung
      transplantation.

PMID- 7813297
TI  - Survival in a case of massive paraquat ingestion.
AB  - Serious exposure to the herbicide paraquat usually results in death, either due
      to gastrointestinal caustic lesions, shock, and acute respiratory distress
      syndrome or related to the progressive development of pulmonary fibrosis
      associated with refractory hypoxemia. We report a case of suicidal paraquat
      ingestion in a 59-year-old man. Most of the indicators of poor prognosis were
      encountered in this patient. Treatment consisted of early digestive
      decontamination and hemodialysis, followed by antioxidant therapy, including the
      administration of deferoxamine (100 mg/kg in 24 h) and a continuous infusion of
      acetylcysteine (300 mg/kg/d during 3 weeks). The patient only developed a
      nonoliguric acute renal failure, a mild alteration of liver tests, and an
      impairment of CO transfer factor without any respiratory complaint. Renal and
      hepatic disturbances completely resolved within 1 month, whereas CO transfer
      factor remained altered 14 months later. This observation suggests that early
      administration of an antioxidant therapy, including deferoxamine and
      acetylcysteine could be usefully associated with measures that prevent digestive
      absorption or enhance elimination to limit systemic toxicity in potentially fatal
      paraquat poisoning.

PMID- 7813298
TI  - Aging effects on cough reflex.

PMID- 7813299
TI  - Corynebacterium parvum pleurodesis.

PMID- 7813300
TI  - High-resolution computed tomography scan in Pneumocystis carinii pneumonia.

PMID- 7813301
TI  - Mycobacterium avium complex lung disease in women.

PMID- 7813302
TI  - Hospital-acquired morbidity and circadian rhythms in patients in the ICU.

PMID- 7813304
TI  - Venous thromboembolism prophylaxis, or lack of...

PMID- 7813305
TI  - The diagnosis of pulmonary embolism. When will we ever learn?

PMID- 7813303
TI  - An unusual complication of central venous catheterization.

PMID- 7813306
TI  - Myocardial infarction with angiographically normal coronary arteries.
AB  - To determine the prevalence rate and clinical and hemodynamic profile of patients
      with myocardial infarction (MI) with angiographically normal coronary arteries,
      we analyzed 3,403 consecutive angiograms performed within a 4.5-year period. Of
      these studies, 1,124 were performed following an acute MI. Through a computerized
      search, 12 patients were identified who had documented MI with normal or
      insignificant (< 30% stenosis in one epicardial vessel only) coronary disease. Q
      wave MI developed in five patients (group A) and non-Q-wave MI developed in seven
      patients (group B). Group A patients were all men whereas group B patients were
      all women. Overall, group A patients were younger (p = 0.003), had a longer
      smoking history (p = 0.008), and a higher cardiac index (p = 0.005). In ten
      patients, areas of localized dyskinesia or hypokinesia were shown on left
      ventricular cineangiography. Mitral valve prolapse was present in four of the
      patients and varying degrees of mitral regurgitation were identified in another
      six. The prevalence rate of MI with angiographically normal coronary arteries was
      1% in this study. This entity had a bimodal age and sex distribution: a younger
      age group, all men, with a stronger cigarette smoking history who had Q-wave MI
      vs an older age group, all women, and no significant association with cigarette
      smoking who developed non-Q-wave MI. A mean follow-up of 4 years demonstrated a
      favorable prognosis in both groups.

PMID- 7813307
TI  - Radiofrequency ablation therapy in concealed left free wall accessory pathway
      with decremental conduction.
AB  - An electrophysiologic study followed by transcatheter radiofrequency ablation
      therapy was performed in two adult patients with a permanent form of junctional
      tachycardia. Both patients had no structural heart disease and exhibited a normal
      resting ECG. The P wave during tachycardia was negative in leads 1, 3, and aVF,
      biphasic over V6, and positive in V1 and aVL in both patients, while the P-R/R-P
      interval ratio during tachycardia was 0.82 and 0.36, respectively, in both
      patients. Both patients displayed an eccentric atrial activation sequence with
      the earliest atrial activation occurring at the distal coronary sinus and a
      decremental retrograde conduction property during incremental ventricular pacing,
      suggesting the presence of a concealed slowly conducting left free wall accessory
      pathway. The tachycardia used the normal atrioventricular pathway for anterograde
      conduction and the concealed show left accessory pathway for retrograde
      conduction. It was terminated following adenosine administration in both
      patients; termination of tachycardia was due to a block in the retrograde
      accessory pathway in one patient and due to a block in the atrioventricular node
      in the other patient. Radiofrequency ablation was performed by the retrograde
      transaortic approach. The radiofrequency f4p4ent was delivered to the site of the
      earliest atrial activation during tachycardia at the ventricular aspect of the
      mitral annulus. The successful ablation site had a ventriculoatrial (VA) interval
      of 120 and 130 ms, respectively, and was located at the posterolateral and
      lateral aspects of the mitral annulus. Following ablation, there was no VA
      conduction; however, conduction through the normal atrioventricular pathway was
      noted during isoproterenol infusion in both patients. There was no induction of
      tachycardia. This study demonstrates that the permanent form of junctional
      tachycardia in adults can incorporate a concealed left free wall accessory
      pathway with a decremental property. Radiofrequency ablation therapy is effective
      and safe in this form of arrhythmia.

PMID- 7813308
TI  - Role of pericardial constraint for right ventricular function in humans.
AB  - STUDY OBJECTIVE: To analyze the extent of pericardial constraint on right
      ventricular function in humans. PATIENTS AND METHODS: Twenty patients, 59 +/- 2
      (mean +/- SEM) years old, undergoing coronary bypass surgery. Right ventricular
      volumes and pressures were evaluated using a rapid response Swan-Ganz
      thermodilution catheter. INTERVENTIONS: Parameters were determined before and
      after pericardiotomy, both before and during increased right ventricular systolic
      pressure by partial compression of the pulmonary artery (before pulmonary
      compression: 25 +/- 1 mm Hg; during: 39 +/- 1 mm Hg). RESULTS: Pericardiotomy
      alone did not significantly affect right ventricular end-diastolic volume
      (before: 79 +/- 4 mL m-2; after: 78 +/- 3 mL m-2), right ventricular ejection
      fraction (before: 48 +/- 1%; after: 48 +/- 2%), and right atrial pressure
      (before: 4.3 +/- 0.8 mm Hg; after: 4.3 +/- 0.7 mm Hg). Before pericardiotomy, the
      increase in right ventricular afterload significantly increased right atrial
      pressure (to 5.5 +/- 0.7 mm Hg, p < 0.05) and reduced right ventricular ejection
      fraction (to 43 +/- 2%, p < 0.01). Right ventricular end-diastolic volume
      remained unchanged. After pericardiotomy, the increase in right ventricular
      afterload significantly increased right ventricular end-diastolic volume (to 85
      +/- 3 mL m-2, p < 0.01) and also reduced right ventricular ejection fraction (to
      42 +/- 2%, p < 0.01), while right atrial pressure was not significantly changed.
      During increased right ventricular afterload, the right ventricular diastolic
      pressure-volume relation was shifted rightward. CONCLUSIONS: At normal levels of
      right ventricular diastolic filling, the pericardium does not exert constraining
      effects on right ventricular function. However, with increasing levels of right
      ventricular preload, pericardial constraint significantly influences right
      ventricular function in humans.

PMID- 7813309
TI  - Pulmonary fibroproliferation and death in patients with late ARDS.

PMID- 7813310
TI  - Pulmonary hypertension and right heart failure in patients with beta-thalassemia
      intermedia.
AB  - We analyzed seven patients with beta-thalassemia intermedia presenting with
      congestive heart failure secondary to pulmonary hypertension. This condition has
      been recognized only recently as part of the clinical spectrum of beta
      thalassemia. Our group of patients included two men and five women with the
      clinical picture and laboratory data typical of beta-thalassemia intermedia. The
      mean age was 37.7 +/- 11.4 years, mean hematocrit value was 28.5 +/- 1.8%, mean
      number of transfused blood units was 171 +/- 153, and mean serum ferritin levels
      were 4,428 +/- 2,006 ng/mL. All but one of these patients had undergone
      splenectomy. Common findings of the investigative procedures include the
      following: dilation of the main pulmonary artery and cardiac enlargement in the
      chest radiograph; signs of right ventricular hypertrophy in the ECG; and dilated
      right ventricle with good left ventricular function in the echo study. Right
      heart catheterization showed the pulmonary systolic pressure to range from 55 to
      90 mm Hg (74.1 +/- 10.3), pulmonary diastolic pressure from 25 to 50 mm Hg (37.7
      +/- 8.7), mean pressure from 35 to 60 mm Hg (49.7 +/- 7.9), and pulmonary
      vascular resistance from 267 to 667 dynes.s.cm-5. Pulmonary capillary wedge
      pressure was within the normal range of values. The pathophysiologic condition of
      pulmonary hypertension in these patients is most probably associated with beta
      thalassemia. There are mechanisms that increase cardiac output and at the same
      time restrict the pulmonary vascular bed. The results of this study imply that
      treatment decisions should be reconsidered for such patients.

PMID- 7813311
TI  - Comparative acute effects of adenosine and prostacyclin in primary pulmonary
      hypertension.
AB  - Vasodilators have been a main focus of therapy for primary pulmonary
      hypertension. Adenosine and prostacyclin have been shown to reduce pulmonary
      vascular resistance acutely in these patients. In order to compare the acute
      hemodynamic effects of adenosine and prostacyclin, ten patients with severe
      primary pulmonary hypertension, unresponsive to medical therapy, were studied.
      After baseline hemodynamics were obtained, an adenosine infusion, 50 to 100
      ng/kg/min, was begun and titrated to the maximum tolerated dose. Hemodynamics
      were allowed to return to baseline, and thereafter, a prostacyclin infusion was
      begun at 2 ng/kg/min, and titrated to the maximum tolerated dose. Overall,
      adenosine (200 +/- 53 ng/kg/min) produced a 33 +/- 18% (p < 0.001) fall in
      pulmonary vascular resistance and a 52 +/- 25% (p < 0.001) increase in cardiac
      output with no effect on pulmonary or systemic arterial pressures. Prostacyclin
      (8 +/- 4 ng/kg/min) caused a 22 +/- 18% (p < 0.01) fall in pulmonary vascular
      resistance and a 25 +/- 26% (p < 0.05) increase in cardiac output with a 14 +/-
      6% (p < 0.001) decrease in systemic arterial pressure, but no change in pulmonary
      arterial pressure. The effects of adenosine and prostacyclin on pulmonary
      vascular resistance were similar (r = 0.70, r2 = 0.49, p = 0.02). Adenosine and
      prostacyclin have similar hemodynamic effects acutely in primary pulmonary
      hypertension. Adenosine may be useful as a test of the potential for long-term
      prostacyclin therapy in patients with primary pulmonary hypertension.

PMID- 7813312
TI  - Nasal continuous positive airway pressure for nonapneic snoring?
AB  - The feasibility of nasal continuous positive airway pressure (CPAP) for heavy
      snoring associated with daytime sleepiness was studied in 118 consecutive
      patients with an apnea hypopnea index below 5. Fifty-nine of them reported
      daytime sleepiness in a questionnaire and were offered treatment with nasal CPAP.
      Whereas 48 patients refused it, the remaining 11 (19%) accepted nasal CPAP for
      home therapy. Acceptors and refusers did not differ in sleep structure, but
      acceptors had slightly more sleep-disordered breathing events per hour of sleep
      than refusers. The pressure needed to abolish snoring in these 11 patients was
      7.3 +/- 1.6 cm H2O. Six months after prescription, the built-in time counters of
      the patients' devices were read. By dividing the hours of operation by the days
      since initiation of treatment, we found a mean daily use time of only 2.8 +/- 1.5
      h. Nevertheless, eight patients (73%) reported that their sleepiness had improved
      with therapy. We conclude that only a minority of nonapneic snorers accept
      treatment with nasal CPAP on a long-term basis and that this subgroup is not
      predictable from polysomnography.

PMID- 7813313
TI  - Does cardiac dysfunction cause pulmonary restriction?

PMID- 7813314
TI  - CPAP titration for sleep apnea using a split-night protocol.
AB  - We studied 107 patients with sleep-disordered breathing to confirm the
      effectiveness of continuous positive airway pressure (CPAP) titration using a
      split-night protocol. Patients spent two consecutive nights in our laboratory
      with complete polysomnography. On the first night, we applied a split-night
      protocol; the first half of the night was used as a baseline (B), and after a
      diagnosis was made, CPAP was applied during the second half of the night (SN). On
      the second night (2N), patients spent the entire night on CPAP to confirm the
      effectiveness of CPAP treatment. The SN and 2N both revealed a significant
      reduction in arousal index (37.8 +/- 27.9 on B, 13.2 +/- 12.1 on SN, 11.4 +/- 8.0
      on 2N, values are mean +/- SD, p < 0.001), apnea hypopnea index (AHI) (23.6 +/-
      26.3/h on B, 3.0 +/- 3.7/h on SN, 2.4 +/- 2.6/h on 2N, p < 0.001), percent total
      sleep time below 90% SaO2 (21.0 +/- 27.2% on B, 8.2 +/- 13.8% on SN, 4.9 +/-
      10.2% on 2N, p < 0.001), and percent total sleep time below 80% SaO2 (1.1 +/-
      3.8% on B, 0.0 +/- 0.1% on SN, 0.1 +/- 0.5% on 2N, p < 0.001). There were no
      significant differences between the SN and the 2N for these measurements. Final
      CPAP pressure was significantly lower at the end of the SN when compared with the
      2N (8.8 +/- 2.7 cm H2O on SN, vs 10.3 +/- 2.8 cm H2O on 2N, p < 0.001). When
      patients were divided into three groups (AHI < 20, n = 69; 20 < AHI < 40, n = 18;
      AHI > 40, n = 20), the final CPAP pressure was different only in the group with
      AHI < 20 (8.1 +/- 2.3 cm H2O on SN, 9.6 +/- 2.3 cm H2O on 2N, p < 0.001). We
      conclude that a split-night protocol may be sufficient to determine the effective
      CPAP pressure, especially in patients with an AHI > 20.

PMID- 7813315
TI  - The effect of electrical stimulation on obstructive sleep apnea syndrome.
AB  - Patients with severe obstructive sleep apnea polygraphically documented underwent
      electrical stimulation treatment trials. Submental and intraoral stimulations
      were applied during waking and during nocturnal sleep. The stimulation was
      applied using a custom-designed neuromuscular electrical stimulator (EdenTec
      Corp) providing symmetric biphasic constant voltage pulses. Pulse duration of
      each phase was set to 80 microseconds based on a subjective evaluation of pulse
      durations from 80 to 300 microseconds to minimize sensation while generating
      equivalent motor responses. Pulse repetition rate was set to 50 pulses per
      second. Cephalometric radiographs and endoscopies were obtained with and without
      stimulations during waking. Most commonly, stimulations induced alpha EEG
      arousals. Submental subcutaneous stimulation induced good contractions of
      platysmal muscles but had no impact on the upper airway. Intraoral stimulation
      induced clear tongue muscle movements but with change of shape of the upper
      airway and posterior movements of the tongue. Each time a breakage of apnea was
      noted, it was associated with a time-linked alpha EEG arousal. The results
      obtained by us and others do not, at this time, give convincing support for the
      use of electrical stimulation using submental surface or intraoral electrodes as
      a viable approach for effective control of obstructive sleep apnea syndrome
      symptoms.

PMID- 7813316
TI  - CD4 T lymphocyte count and the radiographic presentation of pulmonary
      tuberculosis. A study of the relationship between these factors in patients with
      human immunodeficiency virus infection.
AB  - BACKGROUND: Pulmonary infection and tumor in the AIDS population has a variable
      clinical and radiographic presentation. The association between the radiographic
      presentation of pulmonary tuberculosis and CD4 T lymphocyte count in the HIV
      infected patient is investigated in order to provide an empirical approach for
      early diagnosis, treatment, and isolation of infected subjects. METHODS: A
      retrospective analysis of chest radiographs, CD4 T lymphocyte counts, and
      clinical history of 35 subjects from 3 urban hospitals was performed. All
      subjects were HIV-seropositive and had culture-proven pulmonary tuberculosis.
      Radiographs were evaluated for the presence of either a pattern characteristic of
      post-primary tuberculosis (typical pattern) or a pattern uncharacteristic of post
      primary infection (atypical pattern). RESULTS: Twenty-one of 26 subjects with a
      CD4 T lymphocyte count less than 0.20 x 10(9) cells/L, whereas only 1 of 9
      subjects with a CD4 T lymphocyte count of 0.20 x 10(9) cells/L or more presented
      with an atypical pattern of pulmonary tuberculosis (p < 0.001). The mean CD4 T
      lymphocyte counts of those subjects presenting with atypical versus typical
      radiographic pattern of post-primary pulmonary tuberculosis were 0.069 x 10(9)
      cells/L (n = 22) and 0.323 x 10(9) cells/L (n = 13), respectively (p < 0.01).
      Twenty-one of the 22 subjects with an atypical radiographic pattern of pulmonary
      tuberculosis were significantly immunosuppressed (CD4 < 0.20 x 10(9) cells/L).
      Atypical radiographic pattern included diffuse and lower lobar opacities, pleural
      effusion, mediastinal adenopathy, interstitial nodules, and a normal chest
      radiograph. CONCLUSION: AIDS patients presenting with CD4 count less than 0.20 x
      10(9) cells/L and an atypical radiographic pattern for pulmonary tuberculosis are
      at risk for tuberculous infection requiring appropriate treatment and isolation
      until the diagnosis of pulmonary tuberculosis has been excluded.

PMID- 7813317
TI  - Detection of cardiovascular shunts by transesophageal echocardiography in
      patients with pulmonary hypertension of unexplained cause.
AB  - The purpose of this study was to validate the usefulness of transesophageal
      echocardiography (TEE) in the assessment of cardiovascular shunts in patients
      with pulmonary hypertension (PH) of unexplained cause. Twenty-four adult
      patients, 16 women, 8 men; 15 to 70 years of age, with PH of unexplained cause
      were studied. All were examined by transthoracic echocardiography (TTE) and TEE.
      TTE showed the ventricular septal defect in two patients, muscular type in one
      and perimembranous type in the other. TEE showed the atrial septal defect in
      eight patients (secundum type in six and primum type in the remaining) and the
      patient ductus arteriosus in six patients, which were not seen by TTE. The
      ventricular septal defect shown by TTE was also found by TEE. Patients with a
      ventricular septal defect were also associated with a patient ductus arteriosus.
      Among 14 patients with cardiovascular lesions, nine patients displayed a pattern
      of bidirectional shunt, four a pure left-to-right shunt, and the remaining one a
      pure right-to-left shunt. All of the cardiovascular defects could be confirmed by
      passage of the catheter across the defect at cardiac catheterization. In light of
      PH, transthoracic identification of cardiovascular shunts is difficult because of
      the low velocity across the defect. In this study, we found that TEE was superior
      to TTE in detecting and localizing cardiovascular malformations in patient with
      PH.

PMID- 7813318
TI  - Lack of association between atelectasis and fever.
AB  - Postoperative fever occurs in many patients. If no infection is found,
      atelectasis, if present, may be blamed. This study of 100 postoperative cardiac
      surgery patients followed up from day of surgery through the second postoperative
      day with daily portable chest radiographs and continuous bladder thermometry was
      designed to look for an association between atelectasis and fever. The daily
      incidence of atelectasis increased from 43 to 69 to 79%. However, the incidence
      of fever, defined as temperature > or = 38.0 degrees C fell from 37 to 21 to 17%.
      When defined as temperature > or = 38.5 degrees C, the daily incidence of fever
      fell daily from 14 to 3 to 1%. Using chi 2 analysis, no association could be
      found between fever and amount of atelectasis. This contradicts common textbook
      dogma but agrees with previous human study and animal experiments.

PMID- 7813319
TI  - Decision making in nosocomial pneumonia. An analytic approach to the
      interpretation of quantitative bronchoscopic cultures.
AB  - Quantitative cultures of specimens obtained at fiberoptic bronchoscopy have been
      used to diagnose nosocomial pneumonia in research settings, but their clinical
      role remains controversial. We reviewed the literature comparing these culture
      techniques with other accepted methods to diagnose pneumonia in mechanically
      ventilated patients and extracted data to describe the receiver operator
      characteristics (ROC) of quantitative cultures of protected specimen brush (PSB)
      and bronchoalveolar lavage (BAL) samples. Analysis of ROCs reveals that these
      tests have a discriminating power comparable or superior to that of many widely
      accepted routinely used tests. Current data do not suggest that either culture
      technique offers an advantage over the other. Since benefits of antibiotic
      therapy of pneumonia and risks of treatment of noninfected critically ill
      patients are not well quantified, universally applicable recommendations for
      appropriate values to define an abnormal test result cannot logically be made.
      Multiple decision analytic tools show that values lower than those previously
      recommended are more appropriate in patients suspected of having pneumonia unless
      the risk of antibiotic therapy is judged to be extreme. On the basis of these
      findings, we suggest guidelines for clinicians' interpretation of PSB and BAL
      quantitative culture results.

PMID- 7813320
TI  - Influence of three factors on the diagnostic effectiveness of transthoracic
      needle aspiration in pneumonia.
AB  - Prior antibiotic therapy, size of the infiltrate, and the person who performed
      the technique were the three factors that we studied to assess their influence on
      the effectiveness of transthoracic needle aspiration (TNA). Ninety-one patients
      with a diagnosis of severe bacterial pneumonia, who underwent TNA, have been
      included in the study. The technique was carried out with an ultrathin needle
      gauge 25 and without fluoroscopic control. A univariate (UA) and a multivariate
      statistical analysis were made. The sensitivity of TNA was 34.1%. Fifty-seven of
      91 (62.6%) had received antibiotic therapy prior to TNA; sensitivity was higher
      in nontreated patients than in treated patients (p = 0.0033; UA). There were 34
      patients with an infiltrate that was smaller than a lobe (MINLOB); 39 cases
      affected a complete lobe (LOB) and 18 more than one lobe (MAJLOB). The TNA
      sensitivity was higher in LOB cases than in MINLOB cases (p = 0.0004; UA) while
      when comparing LOB cases and MAJLOB cases, sensitivity was higher in the former
      (p = NS; UA). In 28 of 91 cases (30.8%), the TNA was performed by A (a trained
      physician who regularly carries out the technique) and in 63 of 91 cases (69.2%)
      by B (other physicians, 10 in our study, who sporadically perform the technique).
      The TNA sensitivity was higher when the technique was performed by A, although
      this difference was not significant; if we add negative TNA with leukocytes
      present in Gram stains (which would indicate that aspiration was done in the
      correct area) to positive TNA, the difference between A and B was higher (p =
      0.0248). The multivariate statistical analysis confirmed that there are two
      variables that are independently connected to a positive TNA (prior antibiotic
      therapy and size of the infiltrate). As regards the variable "person who carries
      out the technique," a significant association with a positive TNA was not
      established, although the estimations we obtained show a possible clinical
      relevance.

PMID- 7813321
TI  - Pulmonary Embolism: Epidemiology, Pathophysiology, Diagnosis, and Management.
      Proceedings of an international symposium. Florence, Italy.

PMID- 7813322
TI  - Pathology of pulmonary thromboembolism.
AB  - The incidence of pulmonary thromboembolism is hard to assess by the pathologist
      as a result of seasonal variation of embolism and disappearance of emboli by
      thrombolysis. However, the great differences in estimates of the incidence in
      routine hospital autopsies is mainly related to variation in scrutiny of the
      investigation and in size of area searched microscopically. Obstruction of major
      pulmonary arteries almost always results from thromboembolism which is most often
      found in its acute stage. In chronic major vessel embolism, arterial obstruction
      by an organized mass may produce pulmonary hypertension. Recanalization of such a
      mass results in so-called bands and webs. There are no reliable criteria to
      differentiate between emboli and primary thrombi or their sequelae. In
      peripheral, particularly muscular pulmonary arteries, thrombi are most likely
      primary, especially when associated with advanced age and with pulmonary
      hypertension. However, small arteries may be subject to extensive microembolism
      following fragmentation of large thromboemboli. Thrombotic arteriopathy is the
      pulmonary arterial disease based upon either primary thrombosis or embolism. It
      is often associated with pulmonary hypertension, and characterized by irregular,
      nonlaminar, often obliterative, intimal fibrosis. Recanalization channels,
      sometimes widening to separate intravascular fibrous septa, are characteristic
      features. Reversibility of post-thrombotic lesions is very limited.

PMID- 7813323
TI  - The spectrum of pulmonary embolism. Clinicopathologic correlations.
AB  - Pulmonary embolism (PE) is still underdiagnosed even in hospitalized patients. In
      our recent experience, out of 92 postmortem cases of massive or submassive PE,
      only 28% were diagnosed before death, whereas the false-positives accounted only
      for 3% of cases. Similar conclusions have been drawn from large-scale autopsy
      studies performed in Norway and in the United States. The most important causes
      of an incorrect diagnosis are failure to suspect PE, and the protean nature of
      the disease. Remarkable differences actually exist concerning the point of origin
      and the final localization, as well as the size and age of thromboemboli, the
      presence or absence of pulmonary infarction, and the underlying pathology. Often
      a fatal embolus is relatively small but hardly tolerated because of the
      underlying cardiopulmonary situation. Attention should be called to the frequent
      autopsy finding of multiple PEs and pulmonary infarctions of apparently different
      age. This finding is important since it indicates that these patients suffered
      successive embolizations and the eventual death might have been prevented if an
      early diagnosis had been made.

PMID- 7813324
TI  - The role of suspicion in the diagnosis of pulmonary embolism.
AB  - Pulmonary embolism (PE) is largely undiagnosed because clinical suspicion is not
      raised in most instances, and thus, patients with PE go undetected. In this
      paper, we try to define the role of clinical assessment (including chest
      radiography, electrocardiogram, arterial blood gas analysis) in making the
      diagnosis early, accurate, and at low cost, and propose a flow chart to be used
      in clinical practice. All patients with otherwise unexplained dyspnea or chest
      pain should be sent for perfusion lung scintigraphy; accordingly, underdetection
      of PE and mortality of PE should be reduced. If, within 1 h after the clinical
      suspicion has been raised, the above-mentioned simple and noninvasive
      examinations are available, they may be employed to reduce the number of
      unnecessary procedures, without losing patients actually affected by PE. Finally,
      when diagnostic tools are not promptly available, noninvasive techniques may be
      employed to identify patients with the highest probability of PE where to start
      with heparin coverage while waiting for definitive diagnosis.

PMID- 7813325
TI  - Clinical features of pulmonary embolism. Doubts and certainties.
AB  - The diagnosis of pulmonary embolism (PE) can be accurately made by perfusion lung
      scan and pulmonary angiography; however, when these diagnostic techniques are not
      promptly available, simple clinical procedures may be useful to identify patients
      with high probability PE. To this end, collection of clinical data through a
      standardized questionnaire and the use of findings from chest radiograph, ECG,
      and blood gas analysis may raise clinical suspicion and decide on therapeutic
      management. By reviewing published literature and our own experience, we found
      that unexplained dyspnea and chest pain are the most frequent symptoms, and
      sudden onset dyspnea and pleuritic chest pain are the most typical. Chest
      radiograph is abnormal in more than 80% of patients with PE, showing typical
      signs such as "sausage-like" descending pulmonary artery, Westermark sign, etc.
      The ECG may show findings characteristic of PE, such as tachycardia, T wave
      inversion in V1-V2, and PR displacement. Arterial blood gas data frequently
      demonstrate hypoxia and hypocapnia, being helpful in suspecting or excluding PE.
      Recent statistical techniques, such as discriminant or logistic analysis, may be
      applied to the above clinical assessment to refine and improve the noninvasive
      diagnosis of PE.

PMID- 7813327
TI  - Invasive and noninvasive diagnosis of pulmonary embolism. Preliminary results of
      the Prospective Investigative Study of Acute Pulmonary Embolism Diagnosis (PISA
      PED).
AB  - It is maintained that pulmonary angiography is required for confirmation or
      exclusion of pulmonary embolism in the majority of patients suspected of having
      pulmonary embolism. The aim of this study was to reappraise the role of perfusion
      scan in conjunction with clinical assessment in the diagnosis of pulmonary
      embolism and to identify subsets of patients in whom angiography is strictly
      required for definitive diagnosis. At the time of referral, each of 252
      consecutive patients was assigned a clinical probability of pulmonary embolism
      (very likely, possible, unlikely). Perfusion scan was subsequently obtained and
      assigned to one of the following categories: (1) normal; (2) near normal; (3)
      single or multiple wedge-shaped perfusion defects compatible with pulmonary
      embolism (PE+); (4) perfusion defects other than wedge-shaped not compatible with
      pulmonary embolism (PE-). By protocol, angiography had to be obtained in all
      patients with abnormal scan (PE + and PE-). The protocol was completed in 176
      patients (107 with normal/near normal and 69 with abnormal scan in whom a
      definitive diagnosis was reached). The overall rate of correct clinical
      classification was 86%. Sensitivity and specificity of PE+ perfusion scan were 89
      and 92%, respectively. Pulmonary embolism was present in all 37 patients with
      very likely or possible clinical presentation and PE+ scan (positive predictive
      value 100%) and in 2 of 17 cases with low likelihood of pulmonary embolism and PE
      scan (negative predictive value of 88%). These preliminary results indicate that
      pulmonary embolism can be diagnosed noninvasively in the majority of cases and
      that angiography is strictly required only for a minority of patients (21% in
      this study) in whom clinical and perfusion scan assessment are discordant.

PMID- 7813328
TI  - Anticoagulation in the prevention and treatment of pulmonary embolism.
AB  - The anticoagulant agents commonly used in prevention and treatment of pulmonary
      embolism are unfractionated heparin, and more recently, low molecular weight
      heparins, and oral anticoagulants. Unfractionated heparin is the drug of choice
      for prophylaxis and short-term treatment of pulmonary embolism. Oral
      anticoagulants are used for prophylaxis in high risk patients and in long-term
      treatment of pulmonary embolism. Independent overview analysis of clinical trials
      in elective surgery showed a 60 to 70% reduction in the incidence of fatal
      pulmonary embolism in heparin-treated patients when they were compared with
      placebo-treated patients. Low dose heparin has also been shown to be effective in
      reducing venous thromboembolism after myocardial infarction and other serious
      medical disorders. In high risk patients prophylaxis with low molecular weight
      heparins or adjusted doses of unfractionated heparin is recommended. The
      objectives of treating patients with pulmonary embolism are to prevent death, to
      reduce morbidity from the acute event, and to prevent thromboembolic pulmonary
      hypertension. These objectives are achieved by the administration of heparin
      followed by oral anticoagulants. Heparin is generally administered for 7 to 10
      days and is followed by oral anticoagulants. Although widely used and effective
      in the prevention and treatment of pulmonary embolism, unfractionated heparin has
      some pharmacological limitations. Heparin presents an aspecific "nonfunctional"
      binding to plasma proteins such as fibrinogen, factor VIII, vitronectin, and
      fibronectin. This aspecific binding limits the anticoagulant effect of
      unfractionated heparin and, is responsible for the heparin resistance observed in
      some patients with pulmonary embolism as well as of the high intersubject
      variability of the heparin-induced anticoagulant effect. Antithrombotic agents,
      such as low molecular weight heparins and pure thrombin inhibitors (hirudin and
      its analogues), do not specifically bind to plasma protein and they will probably
      improve the efficacy and practicality of the treatment of pulmonary embolism.

PMID- 7813326
TI  - Pulmonary embolism: epidemiology.
AB  - Present evidence suggests that venous thromboembolism is the third most common
      acute cardiovascular disease after cardiac ischemic syndromes and stroke. The
      frequency of the diagnosis of pulmonary embolism (PE) at a given hospital greatly
      increases if a referral unit for PE is set up in the hospital. Pulmonary embolism
      is characterized by a continuous spectrum of severity, from 2 to 3 to 15 to 16
      embolized pulmonary segments (over a total of 19). Morbidity from PE increases
      with age and male sex (males/females ratio: 1.24). In only a minority (10%) of
      patients with PE and/or deep-vein thrombosis (DVT), primary deficiencies of
      coagulation-inhibiting proteins have been shown. Primary abnormalities of the
      fibrinolytic system seem even more rare. On the basis of the clinical conditions
      preceding the embolic episode, patients may be divided into different groups:
      apparently primary or idiopathic PE (40%), surgery or trauma (43%), heart disease
      (12%), neoplastic disease (4%), and systemic disease (1%). Patients with
      apparently primary or idiopathic PE often develop subsequent clinically overt
      cancer (9.1%), whereas surgery or trauma patients rarely do (1.4%). Furthermore,
      the former exhibit a significantly shorter survival than the latter mostly for
      causes of death that reflect increased predisposition to thrombogenesis. Thus, as
      for DVT, it is convenient to consider a primary or idiopathic form also for PE.

PMID- 7813329
TI  - Contemporary pulmonary embolism thrombolysis.
AB  - Lack of familiarity with pulmonary embolism (PE) thrombolysis is understandable
      because most hospitals treat just a few patients each year with recognized
      massive PE. Therefore, most physicians are inexperienced in administering PE
      thrombolysis, even though they utilize these agents routinely for acute
      myocardial infarction. Current estimates are that no more than 10% of patients
      with PE receive thrombolysis in the United States. This situation may be changing
      now, because PE thrombolysis appears to have expanded indications. Contemporary
      PE thrombolysis can now be given with simpler, less expensive protocols than were
      previously available. In the past, this treatment strategy had been rightly
      regarded as a heroic measure that consumed hospital resources and physicians'
      time. Today, PE thrombolysis can be applied with a 2 week "time window," no
      mandatory angiography in many cases, a brief infusion through a peripheral vein,
      and no special laboratory tests.

PMID- 7813330
TI  - Surgical management of unresolved pulmonary embolism. A personal series of 72
      patients.
AB  - Chronic thromboembolic pulmonary hypertension (CT-E PH) is a rare and aberrant
      outcome of acute pulmonary embolism. Because it has become a potentially curable
      form of pulmonary hypertension, the frequency of recognized cases has increased.
      We report a case series of 72 patients with CT-E PH evaluated in our institution
      between 1984 and 1993, and discuss diagnostic clues and therapeutic approaches.
      All patients complained of dyspnea on exertion, a history of acute thromboembolic
      event, and lung murmurs were found in 60% and 17% of patients, respectively. The
      presence of a disorder of coagulation was found in 30% of the patients tested,
      the most common abnormality being lupus anticoagulant. The key noninvasive study
      for diagnosis was the lung perfusion scan which showed at least one segmental or
      larger perfusion defect in all patients. Pulmonary angiography confirmed the
      diagnosis in all cases, and sometimes associated to intravascular ultrasound
      imaging, established the feasibility of thromboendarterectomy. Medical therapy
      included the use of long-term oral anticoagulant, and in the case of lower limb
      venous thrombosis, inferior vena cava filtration. Finally two surgical procedures
      were discussed in selected patients: thromboendarterectomy and lung
      transplantation. Since 1988, eight patients have benefited from lung
      transplantation (six patients are still alive), and 11 patients underwent
      thromboendarterectomy which was successful in 9 patients with a dramatic
      functional and hemodynamic improvement.

PMID- 7813331
TI  - Detection of intracellular lymphoid differentiation antigens by flow cytometry in
      acute lymphoblastic leukemia.
AB  - The value of flow cytometric detection of the intracellular lymphoid
      differentiation antigens CD3 and CD22 in the differential diagnosis of acute
      leukemia was assessed in cases of acute myeloid leukemia (AML), acute
      lymphoblastic leukemia (ALL), and leukemic cell lines. Cells were fixed in 0.25%
      paraformaldehyde at 4 degrees C for 60 min, permeabilized with 0.2% Tween 20 at
      37 degrees C for 15 min, then stained with CD3 or CD22 monoclonal antibodies by
      indirect immunofluorescence. Cytoplasmic CD22 was detected on greater than 20%
      (mean 55%; range 20-87%) of blasts from all 20 cases of precursor-B ALL analyzed.
      The percentage of cells with cytoplasmic CD22 was greater than that with membrane
      CD22 in all except 2 cases of precursor-B ALL. Cytoplasmic CD22 was not detected
      in 8 cases of precursor-T ALL, 4 T-leukemia cell lines, or in 7 cases of AML. In
      contrast, cytoplasmic CD3 was detectable by flow cytometry in all 8 cases of
      precursor-T ALL, but not in precursor-B ALL, pre-B leukemia cell lines, or in
      AML. These results confirm that cytoplasmic CD3 and CD22 are excellent markers of
      the early T and B lineages in ALL and can be reliably detected by flow cytometry.
      This technique should be a valuable addition to routine immunophenotyping for
      classification of acute leukemia.

PMID- 7813332
TI  - Retrospective evaluation of flow cytometry as a platelet crossmatching procedure.
AB  - We performed a retrospective analysis of flow cytometry as a platelet
      crossmatching procedure. Sera from 17 alloimmunized refractory patients were
      tested against 32 donor platelets, which had been stored as platelet-rich plasma
      for up to 36 months. Overall, 14/32 (44%) crossmatches were positive. The mean 1
      h posttransfusion corrected count increments (CCIs) were 9,195 and 2,269 for a
      negative and a positive crossmatch, respectively. The predictive value of a
      positive crossmatch was 86%, whereas the predictive value of a negative
      crossmatch was 56%. When samples with low background fluorescence or with high
      panel-reactive antibody (PRA) levels were evaluated separately, the accuracy of
      the crossmatch improved from 69% to 80%. When compared to the platelet adhesion
      immunofluorescence test (PAIFT) and the standard and antiglobulin-enhanced
      lymphocytotoxicity tests for the detection of HLA antibodies, flow cytometry
      appeared to be more sensitive. We conclude that flow cytometry is a useful
      technique for platelet crossmatching, particularly for alloimmunized patients for
      whom HLA compatible platelets may not be readily available.

PMID- 7813333
TI  - Quality control in flow cytometry for diagnostic pathology: II. A conspectus of
      reference ranges for lymphocyte immunophenotyping.
AB  - Immunophenotyping, as many other clinical assays, is interpreted only in the
      context of reference values obtained from healthy control individuals. While the
      use of these reference values, or ranges, has been commonplace in the clinical
      flow cytometry laboratory for well over a decade, there has been little consensus
      in standardizing how these values should be obtained, analyzed, or expressed.
      This report reviews the variables to be considered in establishing reference
      ranges and statistical methods which can be used. Additionally, examples are
      given of previously published reference ranges for a variety of specimens often
      submitted for immunophenotyping.

PMID- 7813334
TI  - Evaluation of flow cytometric methods for diagnosis of chronic granulomatous
      disease variants under routine laboratory conditions.
AB  - Neutrophils from 50 pediatric patients with normal phagocyte functions, from 150
      healthy adults, from 10 chronic granulomatous disease (CGD)-patients (4 CGD+),
      and from 18 X-linked carriers for CGD have been tested for their production of
      H2O2 using staining with dihydrorhodamine 123 and subsequent flow cytometry.
      Additionally, neutrophils from three patients with myeloperoxidase deficiency
      were assessed. Cells were activated to produce H2O2 by the phorbol ester phorbol
      myristate-acetate (PMA) and by phagocytosis of Escherichia coli bacteria. To
      evaluate the sensitivity of the method, H2O2-production by neutrophils which was
      inhibited by different concentrations of diphenyljodonium (DPI) was measured. The
      results were compared to those from other methods (NBT-testing, cytochrome c
      reduction, and especially chemiluminescence). Normal values and ranges of scatter
      profile were evaluated in terms of peak channel fluorescence: 97% > 700, x = 840
      +/- 59 (S.D.), 97% < 890, for pediatric patients. Normal quantitative values also
      resulted from small blood samples of infants (< 1 year, n = 6, x = 830 +/- 52).
      For CGD+ (n = 4) the results were clearly far below the normal range. In
      indicating decreased production of reactive oxygen intermediates the method was
      at least as sensitive as lucigenin enhanced chemiluminescence. Cytochrome b558
      expression of neutrophils from patients and healthy controls was established by
      flow cytometry following staining with the monoclonal antibody 7D5. The normal
      range was 97% > 485, 97% < 680, peak channel fluorescence. We conclude that flow
      cytometric routine diagnostics of CGD can easily enhance the reliability of
      recognition and the yield of information about this disease compared to
      conventional methods.

PMID- 7813335
TI  - Recall of informed consent after endoscopic procedures.
AB  - PURPOSE: The aim of this study was to determine if recall of informed consent is
      affected by the timing of obtaining informed consent before endoscopic
      procedures. METHODS: Sixty patients scheduled for colonoscopy or
      esophagogastroduodenoscopy were enrolled in this prospective, randomized study.
      Each patient received informed consent 24 to 72 hours or immediately before the
      procedure, and follow-up occurred one to three days postprocedure. RESULTS: There
      was no statistically significant difference in recall of informed consent or the
      individual elements of informed consent (indication, risks, benefits,
      alternatives) between the two groups. CONCLUSION: Recall of informed consent is
      similar whether consent is obtained immediately or several days before endoscopic
      procedures.

PMID- 7813336
TI  - Pouchitis--a poorly understood entity.
AB  - Pouchitis is an increasing drawback to patients who undergo ileal pouch-anal
      anastomosis for ulcerative colitis; complication overshadows the overall good
      functional results of this sphincter-saving operation. There is a need for
      cooperative, multicenter, and longitudinal studies of patients undergoing ileal
      pouch-anal anastomosis, to unravel the etiology and pathophysiology of pouchitis.
      Because of the absence of a mucosal inflammation before pouch construction,
      patients operated on for familial adenomatous polyposis are the perfect control
      group. Thus, it may be possible to elucidate and define the sequence that leads
      to pouchitis, including overgrowth of a colonic type flora, transformation of the
      histology to an epithelium with colonic features, an altered biochemical milieu
      in the lumen (volatile fatty acids, secondary bile acids), and changes in mucosal
      defense mechanisms.

PMID- 7813338
TI  - Randomized trial of internal anal sphincter plication with pelvic floor repair
      for neuropathic fecal incontinence.
AB  - PURPOSE: This study was designed to examine the role of adjuvant internal anal
      sphincter plication in women with neuropathic fecal incontinence undergoing
      pelvic floor repair. METHODS: We completed a randomized trial with symptomatic
      and physiologic assessment before and after surgery. RESULTS: There was no
      symptomatic advantage of adding internal sphincter plication; the mean
      improvement of functional score was 3.61 +/- 1.82 (standard deviation; P < 0.01)
      following pelvic floor repair alone compared with 2.80 +/- 1.66 (standard
      deviation; P < 0.01) when adjuvant internal and sphincter plication was added.
      The addition of internal sphincter plication was associated with a significant
      fall in maximum anal resting and squeezing pressures (P < 0.01). CONCLUSIONS:
      Addition of internal sphincter plication is not advised in women with neuropathic
      fecal incontinence treated by pelvic floor repair.

PMID- 7813339
TI  - Long-term results of curative resection of "minimally invasive" colorectal
      cancer.
AB  - PURPOSE: The aim of this study was to determine the long-term outcome after
      curative resection of colorectal cancers that extend only into the submucosa
      ("minimally invasive") and to evaluate potential histologic predictors of lymph
      node metastases. METHODS: Seventy-nine patients who underwent curative resection
      of minimally invasive colorectal cancer and were followed for at least five years
      were studied retrospectively. RESULTS: The series was comprised of 53 men and 26
      women, with a mean age of 61 years. The lesion was in the colon in 47 patients
      and the rectosigmoid or rectum in 32 patients. Open surgery followed attempted
      endoscopic tumor removal in 25 patients. Lymph node metastasis, found in 11/79
      patients (13.9 percent), was associated with worse outcome: 36.4 percent of
      node(+) patients developed recurrence, vs. only 5.9 percent of node(-) patients
      (P < 0.005). The cumulative survival rate was also worse in node(+) vs. node(-)
      patients: 72.7 percent vs. 91.1 percent at five years (P < 0.05) and 45.5 percent
      vs. 65.3 percent at ten years (P < 0.05). Five histopathologic characteristics
      were identified as risk factors for lymph node metastasis: 1) small clusters of
      undifferentiated cancer cells ahead of the invasive front of the lesion ("tumor
      budding"); 2) a poorly demarcated invasive front; 3) moderately or poorly
      differentiated cancer cells in the invasive front; 4) extension of the tumor to
      the middle or deep submucosal layer; 5) cancer cells in lymphatics. Whereas
      patients with three or fewer risk factors had no nodal spread, the rate of lymph
      node involvement with four or more risk factors was 33.3 percent and 66.7
      percent, respectively. CONCLUSIONS: Metastasis is not infrequent in "minimally
      invasive" colorectal cancer. Appropriate bowel resection with lymph node
      dissection is indicated if such a lesion exhibits more than three histologic risk
      factors for metastasis.

PMID- 7813337
TI  - Improving patient safety with transdermal-fentanyl for post-hemorrhoidectomy
      pain.

PMID- 7813340
TI  - Striated anal sphincter electromyography in idiopathic fecal incontinence.
AB  - PURPOSE: This study was designed to determine the importance of innervation of
      striated anal sphincters, one of the most important structures in idiopathic
      fecal incontinence. METHODS: Forty-three idiopathic, fecally incontinent patients
      (40 women and 3 men; mean age, 57.2 +/- 11 (range, 33-77) years) underwent
      anorectal manometry and sphincteric electromyography. On the basis of
      electromyographic findings, patients were subdivided into three groups: Group A
      consisted of 21 patients with normal electromyography; Group B consisted of 14
      patients with moderate denervation; Group C consisted of 8 patients with severe
      denervation. Manometric results from the patients were compared with those from
      15 healthy subjects (8 women and 7 men; mean age, 35 +/- 12 (range, 15-55)
      years). RESULTS: Incontinent patients had a shorter anal canal (P = 0.005), and
      anal canal pressure was lower at rest (P < 0.001), at contraction (P < 0.001),
      and at coughing (P < 0.001); rectal distention and rectal compliance were reduced
      (maximum tolerated volume, P < 0.003; compliance at 200 ml, P = 0.03; at 250, P <
      0.005; at 300 ml, P = 0.03). No statistically significant differences were found
      between the manometric results of the three different groups of patients. A
      statistically significant linear correlation was reached by comparing the
      clinical severity of fecal incontinence with age (P = 0.02) and some other
      manometric parameters: the pressure of the anal canal at rest (P < 0.001) and at
      contraction (P < 0.01); rectal compliance at 50 ml (P = 0.03), 100 ml (P =
      0.004), and 150 ml (P = 0.004). CONCLUSION: Clinical severity of fecal
      incontinence is correlated with some manometric parameters. Severity of
      denervation of the anal striated sphincters does not appear to influence severity
      of fecal incontinence.

PMID- 7813341
TI  - Rectal compliance determined by rectal endosonography. A new application of
      endosonography.
AB  - PURPOSE: The aim of this study was to develop a method for determination of
      rectal compliance that allows direct measurement of corresponding changes in the
      rectal cross-sectional area or perimeter and rectal pressure. METHODS: We
      developed an anal probe for transrectal endosonography. The probe was tested in
      vitro, and rectal compliance of six healthy patients was determined. RESULTS: In
      vitro measurements proved the method to be well reproducible. The method allowed
      calculation of an endosonographic rectal compliance, which correlated well with
      rectal compliance measured by the standard method. CONCLUSION: Endosonographic
      determination of rectal compliance is possible, and the endosonographic method
      may give a more precise and reproducible estimation of rectal compliance.

PMID- 7813342
TI  - Colorectal neoplasia in patients with ulcerative colitis and primary sclerosing
      cholangitis.
AB  - PURPOSE: Most patients with primary sclerosing cholangitis also have ulcerative
      colitis. It has been suggested that in the presence of primary sclerosing
      cholangitis the risk of colorectal dysplasia and carcinoma is greater than in
      patients with ulcerative colitis alone. METHODS: In a retrospective study, we
      evaluated the possibility of colorectal cancer or dysplasia in 35 consecutive
      patients with primary sclerosing cholangitis and ulcerative colitis seen at The
      Johns Hopkins Hospital between 1979 and 1991. RESULTS: Thirteen of the 35
      patients (37 percent) with ulcerative colitis and primary sclerosing cholangitis
      had colorectal neoplasia (5 with adenocarcinoma and 8 with dysplasia). In the 27
      patients undergoing colonoscopic biopsy surveillance, the cumulative incidence at
      28 years of colorectal cancer was 18.5 percent and for colorectal dysplasia it
      was 29.6 percent. The high incidence of colorectal cancer was less than the rate
      of colorectal cancer in patients with extensive colitis of childhood onset
      without primary sclerosing cholangitis (35 percent), but the rate of colorectal
      cancer and dysplasia (48.1 percent) is similar to the highest rates of cancer
      noted in the comparison group. Because patients had subtle, quiescent colitis, a
      short time from diagnosis of ulcerative colitis to diagnosis of colorectal
      neoplasia was noted (mean, 12.2 +/- 9 years; less than 8 years in 5/13 (38.5
      percent) patients). CONCLUSION: Ulcerative colitis patients with primary
      sclerosing cholangitis appear to have a high frequency of colorectal cancer but a
      rate lower than expected in patients with extensive quiescent ulcerative colitis
      of childhood onset alone. However, exact conclusions are complicated by the high
      incidence of colorectal dysplasia found, which portends malignant transformation.
      Because of the subtle nature of colitis, the diagnosis of ulcerative colitis is
      often delayed, and surveillance programs should start as soon as ulcerative
      colitis is diagnosed.

PMID- 7813343
TI  - Operative repair of anovaginal and rectovaginal fistulas.
AB  - PURPOSE: Operative repair of low rectovaginal fistulas should be tailored to the
      specific anatomic defect. Endoanal flap repair frequently provides successful
      fistula closure; however, if substantial injury to the perineal body, anal
      sphincter, or rectovaginal septum exists, a more extensive repair is required. We
      present our experience with 95 consecutive patients, operated for rectovaginal
      fistulas via septal repair after conversion to a fourth degree perineal
      laceration, endoanal flap, or anoperineorrhaphy. METHODS: A retrospective chart
      review was performed. Data collected included etiology, location, size, repair
      type, and degree of anal continence. All patients received standard mechanical
      and antibiotic bowel preparation and parenteral antibiotics. No covering stomas
      were used. RESULTS: Fistula etiology included obstetric injury (N = 77), perianal
      cryptoglandular infection (N = 15), and other (N = 3). Thirty-one patients had
      previous unsuccessful repairs. Types of repairs were fourth degree perineal
      laceration (38), endoanal flap (19), and anoperineorrhaphy (38). Excellent or
      good functional results occurred in 92 patients (97 percent). Similar success
      occurred in patients with previous failed repairs (90 percent excellent or good).
      The recurrence rate was 3 percent. There were no outcome differences between
      techniques. CONCLUSION: We believe that all three types of repair for
      rectovaginal fistulas result in a high cure rate, thereby allowing operative
      technique to be tailored to the anatomic defects present. This approach should
      allow for optimal functional outcome.

PMID- 7813344
TI  - Anatomic site distribution of colon cancer by race and other colon cancer risk
      factors.
AB  - PURPOSE: Black patients with colon cancer are more likely to have poorer survival
      from colon cancer than are white patients. To determine whether anatomic site
      differences might contribute to survival differences, we compared anatomic site
      distributions of black and white patients. METHODS: As part of the Black/White
      Cancer Survival Study, we collected medical record data for 1,045 patients from
      Atlanta, New Orleans, and San Francisco/Oakland, newly diagnosed in 1985 or 1986
      and interviewed 745 of them. RESULTS: In polychotomous logistic regression
      analysis, site was related to stage, grade, and histologic type and among women
      with age, parity, and possibly smoking. However, it was not related to race,
      except perhaps among men age 65 and older, among whom blacks were somewhat likely
      to have more transverse and distal, not proximal, cancer. These relations were
      consistent across subgroups and were independent of other factors examined.
      CONCLUSION: Results suggest that site differences are unlikely to contribute to
      poorer survival commonly observed among black colon cancer patients in the United
      States.

PMID- 7813345
TI  - Indeterminate colitis. Long-term outcome in patients after ileal pouch-anal
      anastomosis.
AB  - Uncertainty persists concerning the long-term results of ileal pouch-anal
      anastomosis performed for indeterminate colitis. PURPOSE: This study was designed
      to compare functional outcomes of ileal pouch-anal anastomosis in patients with
      typical chronic ulcerative colitis and indeterminate colitis. METHOD: Seventy-one
      ileoanal pouch patients were identified with a diagnosis of indeterminate
      colitis. Mean follow-up was 56 months. Outcomes were compared with 1,232 chronic
      ulcerative colitis patients after ileal pouch-anal anastomosis. Mean follow-up
      was 60 months. RESULTS: (mean +/- SD) There was no difference in the frequency of
      daily bowel movements (indeterminate colitis, 7 +/- 3, vs. chronic ulcerative
      colitis, 7 +/- 2). Daytime and nighttime incontinence rates were likewise
      similar. Prevalence of pouchitis was identical (33 percent). However, failure
      rate was higher in the indeterminate colitis group (indeterminate colitis, 19
      percent, vs. chronic ulcerative colitis, 8 percent; (P = 0.03)). CONCLUSIONS: At
      a mean of nearly five years after surgery, failure appears to occur more
      frequently in patients with indeterminate colitis than in patients with chronic
      ulcerative colitis. However, the great majority of indeterminate colitis patients
      (> 80 percent) have long-term functional results identical to those of patients
      with chronic ulcerative colitis.

PMID- 7813346
TI  - Factors related to frequency, type, and outcome of anal fistulas in Crohn's
      disease.
AB  - PURPOSE: Relation of clinical factors to frequency, type, and, in particular,
      outcome of anal fistulas in Crohn's disease was studied. METHODS: One hundred
      twelve patients seen in this hospital between January 1972 and June 1993 who
      suffered from Crohn's disease were included in the study. Those 35 (31 percent)
      with anal fistulas were re-examined or interviewed and asked about their perianal
      symptoms and anal control. RESULTS: Rectal involvement of Crohn's disease was
      associated with an increased incidence of anal fistula (49 vs. 17 percent; P <
      0.01), especially high ones (82 vs. 17 percent; P < 0.01). Ten of 18 patients
      with low fistulas underwent fistulotomy; all 10 fistulas healed, but slowly (mean
      healing time, 7.5 months), and 4 of them recurred. Of eight low fistulas managed
      by drainage alone, four healed. Finally, 11 of 18 patients with low fistulas had
      their fistulas heated. Fourteen of 17 patients with high fistulas were primarily
      treated by drainage and 3 by local surgery. Finally, only three patients had
      healed fistulas--two after simple drainage and one after local surgery, and seven
      patients had to undergo proctectomy. Only two patients with low fistulas required
      proctectomy. Eight patients (33 percent) of those 24 with fistulas in whom anal
      continence could be assessed, 5 with local surgery and 3 with drainage alone,
      reported minor defects in anal control. CONCLUSIONS: Fistulotomy is a justifiable
      option with satisfactory results for low symptomatic anal fistulas associated
      with Crohn's disease, although healing may be delayed and some fistulas will
      recur. Outcome of high fistulas is less satisfactory, and proctectomy is
      ultimately required in a number of patients; therefore, for high fistulas a
      conservative approach is primarily recommended.

PMID- 7813347
TI  - What is the desirable stimulus to induce the rectoanal inhibitory reflex?
AB  - PURPOSE: This study was designed to find other methods to induce rectoanal
      inhibitory reflex. METHODS: Twenty healthy children were studied manometrically
      using three different types of stimuli, air, balloon, and water. RESULTS: Reflex
      occurred with all three kinds of stimuli; however, the free-air method was more
      sensitive and convenient than the common inflating balloon method. The lowest
      feeling amount and lowest amount in the free-air method are significantly lower
      than those in the balloon method (P < 0.05). The highest amount in the free-air
      method is significantly lower than those in the balloon method (P < 0.02). The
      highest drop and sustain time in both the free-air and balloon methods are not
      significant. CONCLUSIONS: The internal and sphincter has the function to respond
      to air (flatus). The semiconductor strain gauge catheter is better than the air
      filled or water-filled balloon and water-infused catheter for the study of rectal
      physiology.

PMID- 7813348
TI  - Folate status and adenomatous colonic polyps. A colonoscopically controlled
      study.
AB  - PURPOSE: The aim of our study was to assess any association of folate with
      development of colonic adenomas. METHODS: Serum and red blood cell folate levels
      were measured in 62 colonoscopically and histologically evaluated patients with
      colon adenomas (Group A) and in 50 selected colonoscopically negative controls
      (Group B). Patients with colon polyps underwent colonoscopy for alterations of
      bowel habits or abdominal pain, and detected polyps were found coincidentally.
      Controls underwent colonoscopy for alterations of bowel habits or abdominal pain.
      There was no difference in hematocrit between the two groups. RESULTS: The mean
      serum folate level in patients with colonic adenomas was 4.57 ng/ml +/- 2.8
      standard deviations (SD), and the mean red blood cells folate levels were 536
      ng/ml +/- 273.3 (SD). In controls the mean folate levels in serum and red blood
      cells were 5.09 ng/ml +/- 2.7 (SD) and 743.8 ng/ml +/- 297.1 (SD), respectively.
      The red blood cell folate level of colon adenoma patients was statistically lower
      than the respective level of controls at a highly significant level (P < 0.01).
      CONCLUSIONS: We suggest that depressed red blood cell folate levels are
      associated with development of colonic adenomas.

PMID- 7813349
TI  - Lateral sphincterotomy compared with anal advancement flap for chronic anal
      fissure.
AB  - PURPOSE: This study was designed to assess differences between lateral internal
      anal sphincterotomy and anal advancement flap for chronic anal fissure. METHODS:
      Forty patients with chronic anal fissure were prospectively studied. Patients
      randomized to the sphincterotomy group (n = 20; median age, 34 (range, 16-61)
      years) underwent lateral internal anal sphincterotomy. Patients randomized to the
      flap group (n = 20; median age, 32 (range, 20-44) years) had an anal advancement
      flap. RESULTS: All fissures in the sphincterotomy group healed following surgery
      compared with three patients that failed to heal in the flap group (P = 0.12). No
      patient in either group was incontinent to any degree following surgery. Patient
      satisfaction with surgery was similar in both groups. CONCLUSION: Anal
      advancement flap is an alternative to lateral sphincterotomy for chronic anal
      fissure.

PMID- 7813351
TI  - Computer-generated profiles of the anal canal in patients with anal fissure.
AB  - PURPOSE: The pathophysiology of anal fissure remains poorly understood. This
      study examines manometric findings in patients with anal fissure with use of a
      computer-assisted system, which helps to standardize manometric performance as
      well as generating longitudinal and cross-sectional profiles of the anal canal.
      METHODS: Water-perfused, eight-channel, computer-assisted manometry was performed
      on 12 patients with chronic anal fissure and compared with 12 age-matched and sex
      matched controls. RESULTS: Mean maximum average resting pressure (MARP) was 120.5
      mmHg in patients and 82.6 mmHg in controls (P = 0.0005). Pain was felt during
      manometry in six patients. In these patients, MARP was 123.2 mmHg, and, in the
      other six patients, MARP was 117.8 mmHg. Sphincter length was 4.72 cm, and the
      high pressure zone or that part of the sphincter with pressure more than 50
      percent of MARP) was 2.78 cm in length. The high pressure zone/sphincter length
      ratio was 58 percent compared with 48 percent in controls. Longitudinal profile
      was bell shaped. Elevated pressures were not confined to the site of the fissure.
      Cross-sectional analysis showed higher anterior pressures in the distal
      sphincter. Ultraslow waves were seen in as many as 91 percent of patients and 73
      percent of controls. However, ultraslow wave amplitude was 31 mmHg in patients
      and 15 mmHg in controls (P = 0.03). The rectoanal reflex was normal; overshoot
      was not seen. CONCLUSIONS: The primary abnormality in fissure is persistent
      hypertonia affecting the entire internal sphincter, unrelated to pain. Cross
      sectional pressure profiles may explain the predilection of fissures to occur in
      the posterior midline; other factors must prevent chronic fissures from healing.

PMID- 7813350
TI  - Results of rectocele repair. A prospective study.
AB  - PURPOSE: This study was designed to evaluate the results of rectocele repair and
      parameters that might be useful in selecting patients for this operation.
      METHODS: Twenty-five patients with symptom-giving rectoceles were prospectively
      evaluated with a standardized questionnaire, physical examination, defecography,
      colon transit studies, anorectal manometry, and electrophysiology. Patients
      underwent posterior colporrhaphy and perineorrhaphy. They were followed
      postoperatively (mean, 1.0 year) with the same questionnaire, physical
      examination, defecography, anorectal manometry, and electrophysiology. RESULTS:
      Constipation had improved postoperatively in 21 of 24 constipated patients (88
      percent). At postoperative follow-up 13 patients (52 percent) had no constipation
      symptoms, 8 (32 percent) had occasional symptoms, and 4 (16 percent) had symptoms
      more than once per week. Four patients with rectocele at preoperative
      defecography, but not at physical examination, had favorable outcomes following
      surgery. The majority of patients not using vaginal digitalization preoperatively
      had improved with respect to constipation. All patients with pathologic transit
      studies had various degrees of constipation postoperatively. Constipation was not
      improved in two of five patients with preoperative paradoxic sphincter reaction.
      CONCLUSIONS: Rectocele is one cause of constipation that can be treated with good
      results. Preoperative use of vaginal digitalization is not mandatory for a good
      postoperative result. Defecography is an important complement to physical
      examination. Patients with pathologic transit study might have a less favorable
      outcome of rectocele repair with respect to constipation. More studies about the
      significance of paradoxic sphincter reaction in these patients are indicated.

PMID- 7813352
TI  - Wide resection and reconstruction preserving fecal continence in recurrent anal
      cancer. Report of three cases.
AB  - PURPOSE: A new operation was developed to treat patients with local recurrence of
      cancer at the anal margin after radiotherapy. This operation aims at resection of
      the tumor with oncologically safe margins, preservation of fecal continence, and
      reliable wound healing. METHODS: After intensive radiotherapy, three patients
      with local recurrences of squamous-cell carcinoma of the anus refused to undergo
      abdominoperineal resection. These patients were treated by wide local excision
      and primary reconstruction. Wide local excision included perianal skin with
      subcutis and the anal canal including the internal sphincter up to the dentate
      line. To reconstruct the anus, the rectum was mobilized and brought down to the
      level of the perineum through the external sphincter and anastomosed to bilateral
      biceps femoris myocutaneous flaps. RESULTS: In the first three patients no tumor
      recurrences have occurred, and fecal continence has been good. CONCLUSION: The
      first results with this continence-preserving operation in patients with
      recurrent anal margin cancers after radiotherapy have been encouraging.

PMID- 7813353
TI  - Life-threatening hemorrhage and exsanguination from Crohn's disease. Report of
      four cases.
AB  - PURPOSE AND METHODS: From 1979 through 1991, four patients of 631 admissions (0.6
      percent) for Crohn's disease in Erie, Pennsylvania, presented with life
      threatening gastrointestinal hemorrhage. These and 34 similar cases from the
      medical literature were reviewed to provide a composite of those at risk and
      elucidate appropriate diagnostic and therapeutic maneuvers. RESULTS: The study
      revealed a preponderance of young men (2:1 ratio) with an average age of 35
      (range, 14-89) years, the majority of whom had known Crohn's disease (60 percent)
      for an average of 4.6 (range, 0-18) years. The site of bleeding resembled the
      general distribution for Crohn's disease, with small bowel disease predominating
      (66 percent involved the ileum). The five cases of exsanguination (13 percent of
      the total) were all men with known Crohn's disease (average, 5.8 years) involving
      the ileum alone or in part. Mesenteric arteriography was positive in 17 patients,
      providing precise preoperative localization resulting in no mortality in this
      group. Excluding those who presented with exsanguination, surgery was necessary
      to cease hemorrhage in 91 percent (30/33) of patients. Ileocolectomy was the most
      frequently performed procedure (53 percent). In follow-up, only one patient
      required further surgical resection for recurrent bleeding (3.5 percent), and two
      other patients (7 percent) required further therapy for nonhemorrhagic
      recurrence. CONCLUSION: Crohn's disease may be responsible for life-threatening
      gastrointestinal hemorrhage and even exsanguination. Many of the characteristics
      of these patients resemble the general Crohn's disease population. Surgical
      resection provides excellent palliation. A long-term benign course can be
      expected in this subgroup of Crohn's disease patients.

PMID- 7813354
TI  - Eversion of the rectum. A simplified technical approach to ileoanal anastomosis.
AB  - Eversion of the rectum allows complete excision of the rectum. Here, we describe
      a modification of the stapling technique of ileoanal anastomosis, which leads to
      a safer anastomosis.

PMID- 7813355
TI  - Simple ileal J-pouch construction using an endoscopic stapler.
AB  - An easier method in constructing a J-pouch is described using an endoscopic
      stapler. Although not designed for open procedures, the length of this instrument
      allows the J-loop to slide up the device following each staple application. Close
      opposition of the antimesenteric borders of the ileum is thus more easily
      achieved, telescoping of the bowel is avoided, and the enterostomy does not
      become unnecessarily enlarged.

PMID- 7813356
TI  - Can regulatory proficiency testing by the cytobureaucracy decrease both false
      negatives and cervical cancer deaths?

PMID- 7813358
TI  - Fine-needle aspiration of plasma cell disorders: special emphasis on plasma cell
      subtype.
AB  - Fine-needle aspiration cytology and clinical presentations of 16 cases of plasma
      cell dyscrasias (PCD) have been studied in a period of 6 yr. There were seven
      cases of solitary plasmacytomas of bones, two cases of extramedullary
      plasmacytomas, and seven cases of multiple myelomas. Differential counts of
      mature and immature plasma cells along with presence of cell clumps, mitosis, and
      bi/multinucleations were studied. The cytological findings revealed no
      correlation with the different subtypes of PCDs; however, it was helpful in the
      differential diagnosis. Bone marrowing findings, immunological parameters,
      available histopathology, and X-ray appearances were analysed. Clinical diagnosis
      of PCDs were made in only three cases. Thus fine-needle aspiration biopsy was
      considered as an important diagnostic modality in tissue diagnosis of plasma cell
      tumors, particularly in solitary plasmacytoma of bone and extramedullary
      plasmacytoma.

PMID- 7813357
TI  - p53 immunolocalization in cytology specimens: a study in human esophageal
      carcinoma.
AB  - Immunohistochemical analysis of p53 has become an established method of detecting
      mutated p53. Immunolocalization of p53 has been extensively studied in tissue
      sections of many human neoplasms, but not in cytology specimens. Therefore, we
      performed immunolocalization of p53 in both cytology and tissue preparations
      obtained from the same specimens in 19 cases of human esophageal squamous-cell
      carcinoma. Three different antibodies, PAb1801, DO-7, and CM-1, were employed.
      Positive p53 nuclear immunoreactivity was observed in carcinoma cells, but not in
      noncarcinomatous cells, in both tissue and cytology preparations. The incidence
      of p53 positivity was 53% (10/19) in cytology and 42% (8/19) in tissue, and the
      coincident rate of both results was 89% (17/19). We conclude that
      immunohistochemistry of p53 in cytology is a useful method for detecting p53
      mutations, and may contribute to the diagnosis of malignancy, because it is a
      simple, easy, and rapid technique.

PMID- 7813359
TI  - Simplified nuclear grading of fine-needle aspirates of breast carcinoma:
      concordance with corresponding histologic nuclear grading and flow cytometric
      data.
AB  - Although histologic grading of breast carcinoma is widely practiced by most
      pathologists, cytologic grading of fine-needle aspirates (FNA) of this neoplasm
      is not commonly done. This study addresses the issue of the accuracy of a new
      classification system, a simplified Nuclear Grading (NG) system based on the
      criteria proposed by Black et al. (Surg Gynecol Obstet 1955;100:543) in FNA of
      breast carcinoma. We reviewed 100 cases of breast carcinoma, initially diagnosed
      by fine-needle aspiration biopsy (FNAB) with subsequent histologic confirmation,
      consisting of 94 ductal, five lobular, and one medullary carcinoma. NG of
      Papanicolaou's stained materials were reviewed twice independently by two
      pathologists and then were compared to the original histologic NG. The
      concordance rate with histology ranged from 80-90%. Intraobserver reproducibility
      was 86 and 88%, while interobserver reproducibility ranged from 84-88%. Of the 88
      cases with corresponding flow cytometic (FCM) data, there were 35 diploid and 53
      aneuploid cases. Fifty-nine (95%) of histologic high NG were aneuploid or diploid
      with high S-phase fraction (SPF), while 20 (77%) of histologic low NG were
      diploid with low SPF. This study confirms that nuclear grading of FNA of breast
      carcinoma using a simplified NG system has a high concordance with histology, has
      high intraobserver and interobserver reproducibility, and that this grading
      system correlates well with FCM analysis when tumors are simply divided based on
      NG as high or low grade.

PMID- 7813360
TI  - Expression of proliferating cell nuclear antigen, Ki-67 antigen, estrogen
      receptor protein, and tumor suppressor p53 gene in cytologic samples of breast
      cancer: an immunochemical study with clinical, pathobiological, and histologic
      correlations.
AB  - Sixty-six unselected breast cancers were analyzed in cytologic smears and
      histologic sections for the expression of Ki-67, proliferating cell nuclear
      antigen (PCNA), estrogen receptor protein (ERP), and p53 protein using a standard
      immunochemical method. The results, expressed as both positive cases and
      labelling index (LI), were compared with clinical and pathobiological variables.
      Ki-67 and PCNA immunostaining was seen in all cases, whereas ERP was detectable
      in 46/63 cases and p53 protein in 20/66 cases. The expression of these markers
      was generally lower in cytology than in histology, though the differences were
      not statistically significant. PCNA-LI and Ki-67-LI were closely correlated (P <
      0.001), the mean PCNA:Ki-67 ratio being 0.92 +/- 0.57. Occasional discrepancies,
      however, were found. PCNA and Ki-67 expression was associated with an increase in
      histologic grade and a decrease in ERP content of tumors, whereas p53 was
      statistically associated with no clinical or pathobiological variables. The data
      suggest that proliferative activity and oncogene overexpression may be reliably
      evaluated in breast cancer by FNA cytology, though PCNA is not a suitable
      indicator for cell proliferation. The results do not resolve the issue as to
      whether immunostaining for p53 protein constitutes a dedifferentiation product of
      the tumor, or is a fundamental aspect of the malignant progression. Survival
      studies in a larger series of tumors are thus needed to elucidate this point.

PMID- 7813361
TI  - Hashimoto's thyroiditis: fine-needle aspirations of 50 asymptomatic cases.
AB  - The cytologic findings from 50 cases of asymptomatic Hashimoto's thyroiditis
      diagnosed by fine-needle aspiration are reviewed. All patients were referred for
      fine-needle aspiration by the same physician: 48 because of thyroid enlargement
      and the clinical suspicion of Hashimoto's thyroiditis, two because of a small
      thyroid nodule. Positive antimicrosomal (antithyroid peroxidase) and/or
      antithyroglobulin antibody titers (performed by the same laboratory using the
      same technique) were present in only 25 of 48 patients evaluated. Cytologic
      findings included a predominantly lymphocytic process in 92% of the cases and a
      predominantly oxyphilic (Askanazy/Hurthle) cell process in 8% of the cases. It is
      likely that all patients were in an early stage of the autoimmune process. Our
      data indicate that the incidence of Hashimoto's thyroiditis is considerably
      higher than when recognized only by serologic tests for antibodies.

PMID- 7813362
TI  - Aspiration biopsy cytology of tubular carcinoma of the breast.
AB  - Tubular carcinoma represents a rare, well-differentiated type of breast
      malignancy, characterized by relatively unaggressive clinical behavior. Cytologic
      diagnosis of this subgroup of tumors is considered difficult as cell population
      usually presents in tightly cohesive clusters and shows minimal atypia.
      Cytomorphologic features of 15 examples of histologically proven pure tubular
      carcinomas of the breast are herein reported. If a constellation of morphologic
      criteria is critically evaluated, tubular carcinoma may be diagnosed on cytologic
      specimens. Aspiration biopsy cytology represents an optimal diagnostic tool in
      the preoperative diagnosis of breast masses. Its application to the detection of
      this special type of breast carcinoma permits better planning of therapeutic
      procedures.

PMID- 7813364
TI  - Small round cell tumor with divergent differentiation: cytologic, histologic, and
      ultrastructural findings.
AB  - A case study of desmoplastic small round cell tumor with divergent
      differentiation in a 13-yr-old boy is presented. Clinical, cytologic, histologic,
      immunohistochemical, and ultrastructural findings are reported. There was a close
      correlation between the various histologic and cytologic patterns.
      Immunohistochemical studies revealed strong positivity of many of the tumor cells
      for cytokeratin, vimentin, and desmin. Ultrastructurally, some of the tumor cells
      contained aggregates of cytoplasmic intermediate filaments. Fine-needle
      aspiration biopsy may suggest the diagnosis of desmoplastic small round cell
      tumor. Confirmation of the diagnosis may be provided by immunohistochemistry and
      electromicroscopy.

PMID- 7813363
TI  - Comparative study of interphase cytogenetics, flow cytometric analysis, and
      nuclear grade of fine-needle aspirates of breast carcinoma.
AB  - The correlation between DNA ploidy and S-phase fraction (SPF) by flow cytometry
      (FCM) and the detection of numerical chromosomal abnormalities (NCA) by
      interphase cytogenetics (IC) involving chromosomes 8 and 12 was studied in 20
      human breast lesions (17 breast carcinomas, 2 fibroadenomas, and 1 sclerosing
      adenosis). Initial diagnosis was performed on fine-needle aspiration biopsy
      (FNAB) material with subsequent histologic confirmation. FCM was performed on
      formalin-fixed paraffin-embedded tissue while IC by fluorescence in situ
      hybridization (FISH) was done on alcohol fixed FNAB materials. Sixteen (80%)
      cases showed concordance between FCM and IC with respect to the presence or
      absence of aneuploidy. The remainder of the cases (20%), which were all malignant
      neoplasms, showed discrepancies between the two methods, all four were DNA
      diploid with low SPF by FCM but showed various NCA by IC. Nuclear grades (NG) of
      all the malignant samples were also evaluated and correlated with both FCM and IC
      studies. Although a good correlation was observed between NG and FCM, a better
      correlation was seen between NG and IC. This study shows that although IC by FISH
      correlated well with FCM analysis, it can detect NCA in DNA-diploid, low SPF
      tumors. It also correlates well with the NG of the tumor. The increased
      sensitivity provided by IC in detecting aneuploidy may be of great prognostic
      significance in low stage, DNA-diploid, low SPF breast carcinomas.

PMID- 7813365
TI  - Expression of the pS2 protein and correlation with estrogen receptor status in
      fine-needle aspirates from breast carcinomas.
AB  - A series of 36 cases of breast carcinomas diagnosed by fine-needle aspiration
      were investigated for the presence of estrogen receptors (ER) and the estrogen
      induced pS2 protein. Immunocytochemically ER could be demonstrated in 28
      aspirates, whereas eight were negative. These eight were also negative for the
      pS2 protein. In addition three aspirates with a low score for ER and five with a
      high score for ER were found negative for pS2. Thus, of the 36 cases, 20 were
      found to express the pS2 protein. The presence of the pS2 protein in the tumor
      cells is believed to be a marker of a functional estrogen regulatory system and
      its demonstration may therefore predict clinical responsiveness to hormonal
      therapy.

PMID- 7813366
TI  - Cytodiagnosis of a primary non-Hodgkin's lymphoma of bone.
AB  - We report fine-needle aspiration cytology and histologic findings of a primary
      non-Hodgkin's lymphoma of bone involving the rib and iliac bones. Smears
      contained abnormal lymphoid cells and abundant lymphoglandular bodies, suggesting
      a malignant lymphoproliferative disease. However, histologic sections showed
      nests of tumor cells with extensive cytoplasmic clearing surrounded by sclerosis,
      thus mimicking a carcinoma. Clinical data, radiographic findings, and
      cytohistological correlation led to a final diagnosis of primary non-Hodgkin's
      lymphoma of the bone, confirmed by immunopositive staining for leukocyte common
      antigen CD45 and B-cell associated antigen CD20. It is concluded that finding
      numerous lymphoglandular bodies in bone tumor specimens allows an accurate
      diagnosis of lymphoid tissue. The rarity of bone lymphoma and the misleading
      histologic features can cause considerable difficulty in diagnosing this entity.
      The importance of identifying lymphoglandular bodies and the appropriate use of
      immunochemistry are emphasized.

PMID- 7813367
TI  - Cutaneous T-cell lymphoma diagnosed by fine-needle aspiration: a case report with
      clinical, cytological, and immunophenotypic features.
AB  - A case study of cutaneous T-cell lymphoma in a 40-yr-old Indian male is
      presented. Prominent clinical features consisted of large skin tumours,
      lymphadenopathy, and a rapidly progressive course of development. Aspiration
      smears from tumours, lymph nodes, and bone marrow showed pleomorphic Sezary cells
      and lymphoid blasts. The neoplastic cells stained positively with anti-HLA DR,
      CD1, and CD2 antibodies and showed lack of T-cell subset antigens CD4 and CD8.
      Numerous proliferating cells were identified with 56% of bone marrow cells and
      57% of cells in the dermis staining positively with Ki-67 and PC10 antibodies,
      respectively. This case is reported in view of its uncommon features.

PMID- 7813368
TI  - Pulmonary carcinoid with papillary structure: report of a case with fine-needle
      aspiration cytology.
AB  - Fine-needle aspiration biopsy of a peripheral lung mass in a 44-yr-old man
      revealed a papillary tumor. Histologic examination of the mass, removed by
      lobectomy, demonstrated a pulmonary carcinoid tumor with papillary structure.
      Most papillary tumors of the lung are malignant. Pulmonary carcinoid and
      pulmonary sclerosing hemangioma--benign tumors--have papillary variants. Both
      have been described in fine-needle aspiration specimens and should be included in
      the differential diagnosis of papillary lung tumors. The cytologic features of
      pulmonary carcinoid are described.

PMID- 7813370
TI  - Infarcted intraduct papilloma diagnosed by fine-needle biopsy: a cytologic,
      clinical, and mammographic pitfall.
AB  - Necrosis is a worrisome cytologic feature in breast aspirates which, when paired
      with suspicious clinical and mammographic findings, could potentially result in a
      false positive diagnosis. A 66-yr-old female presented with clinical evidence of
      stage 1 breast carcinoma supported by the mammographic and ultrasound findings. A
      fine-needle biopsy (FNB) revealed extensive necrosis with scattered degenerate
      columnar cells, occasional clusters of hyperchromatic epithelial cells, and a few
      sheets of ductal cells. A cytologic diagnosis of an infarcted intraduct papilloma
      was made. This uncommon diagnosis was subsequently confirmed by open biopsy.
      Cytologic features to distinguish infarcted, necrotic, and papillary breast
      lesions are discussed.

PMID- 7813369
TI  - Cytologic patterns of metastatic thymoma: diagnosis by fine-needle aspiration
      biopsy.
AB  - Thymomas are the most frequent primary tumors of the anterior mediastinum. These
      lesions are slow growing and can be locally invasive, but extrathoracic
      metastases are rare, occurring in less than 2% of cases. Fine-needle aspiration
      biopsy (FNAB) may be helpful in making the diagnosis of metastatic thymoma, with
      or without a clinical history of primary mediastinal thymoma. We report three
      cases of metastatic thymoma diagnosed by FNAB. Each case illustrates a
      distinctive cytologic pattern. While two of the patients had a history of
      histologically confirmed thymoma 11 and 13 years previously, a third patient
      presented with an enlarged supraclavicular lymph node and pulmonary nodules, and
      no prior diagnosis of thymoma. These cases demonstrate that based on distinctive
      cytologic patterns and features, a diagnosis of metastatic thymoma can be made
      with FNAB. Ancillary studies will often confirm the diagnosis.

PMID- 7813371
TI  - Quality assurance programs to meet CLIA requirements.
AB  - CLIA '88 delineates specific quality assurance (QA) practices for cytology
      laboratories in the United States. In addition, there are general requirements
      that all types of clinical laboratories must meet to satisfy the CLIA law and
      regulations. This paper describes the origins and objectives of CLIA and it
      outlines the major sections of the legislation. To satisfy the regulations, every
      laboratory must develop its own quality assurance plan that addresses each of the
      specific conditions and standards. Furthermore, the laboratory must monitor its
      performance and document that, indeed, the QA systems are operating effectively.
      The article then describes the quality assurance plan of the Cytology Department
      of the Wisconsin State Laboratory of Hygiene. The department uses 28 monitors to
      determine compliance with the criteria and standards and to prevent problems in
      its day-to-day operation. When standards are not met or are exceeded, action
      steps are specified.

PMID- 7813372
TI  - Enterobius vermicularis granuloma of the ovary: report of a case with diagnosis
      by intraoperative cytology.

PMID- 7813373
TI  - Diabetic fibrous mastopathy: additional considerations.

PMID- 7813374
TI  - Contribution of scanning laser ophthalmoscopy to the functional investigation of
      subjects with macular holes.
AB  - A study was designed to validate a functional investigation performed with the
      scanning laser ophthalmoscope before surgery for macular holes in 12 eyes: The
      assessment included fundus examination, a functional examination resulting in
      evaluation of the preferred retinal lows, visual acuity and recording of visual
      evoked potentials. The preferred retinal locus was evaluated by presenting a
      small square area, and visual acuity was determined by means of calibrated
      figures. The visual evoked potentials were evoked by three alternating
      checkerboards (check size, 30', 2 Hz) centered over the hole and seen at an angle
      of 6.5 x 6.5 degrees, 2.5 x 2.5 degrees and 6.5 x 6.5 degrees with central
      exclusion of 2.5 x 2.5 degrees. The appearance of the fundus visualized by
      scanning laser ophthalmoscopy consisted of a clear central disk corresponding to
      the hole, surrounded by a very dark ring, associated with a second, less dark
      ring with unclear margins. Fixation was unstable in one case with a visual acuity
      of 20/70. In 11 cases, fixation was localized to the superior retina with a
      visual acuity superior to 20/70. The visual evoked potentials evoked by 6.5 x 6.5
      degrees were discernible in all 12 eyes; visual evoked potential by annular
      stimuli were discernible in 11 cases. The 2.5 x 2.5 degrees stimulus evoked no
      response in eight cases, proving the area of the hole was nonfunctional. A
      response was recorded in the four other cases, where the dimension of the holes
      was less than 2 degrees. The results of this scanning laser ophthalmoscopic
      assessment demonstrated a precise evaluation of the residual macular function in
      the cases of full-thickness macular holes.

PMID- 7813375
TI  - Electro-oculographic changes after local excision of uveal melanoma.
AB  - Standard electro-oculography was performed in 10 patients with malignant
      unilateral uveal melanoma All eyes were treated by means of surgical local
      excision. After a mean +/- standard deviation follow-up of 10.5 +/- 5.5 months
      (range, 6 to 20 months) in the five patients with choroidal melanoma, the electro
      oculographic recordings, which had appeared reduced or flat before the surgery,
      increased significantly just after the local excision. Thereafter the amplitudes
      of the electro-oculographic light peaks were reduced in all cases up to
      extinction, possibly because of a retinal detachment. On the contrary, the
      electro-oculographic value in the five melanomas localized at the iris and
      ciliary body, normal before the surgery, showed a marked and persistent increase
      after surgery, probably related to an 'electric hole' in the globe.

PMID- 7813377
TI  - Electroretinographic findings in congenital oculomotor apraxia (Cogan's
      syndrome).
AB  - We performed visual evoked potential testing and electroretinography in five
      patients with Cogan's oculomotor apraxia. The visual evoked potentials were
      normal, confirming previously reported data. Electroretinograms were abnormal in
      two of the five patients examined. A previous study showed normal
      electroretinogram responses bilaterally in one patient. Our findings suggest the
      existence of two variants of the syndrome; the one with electroretinogram
      anomalies has a worse visual prognosis.

PMID- 7813376
TI  - Electrophysiologic alterations in patients with optic nerve hypoplasia.
AB  - The clinical and electrophysiologic data (electroretinograms and visual evoked
      potentials) were studied in 45 patients with optic nerve hypoplasia. The patients
      were divided into three fairly distinct groups on the basis of their
      electrophysiologic alterations. Group 1 consisted of 13 patients with almost
      extinguished visual evoked potentials and with mild electroretinographic
      alterations. These were the cases that are traditionally recognized as optic
      nerve hypoplasia. The serious visual impairment in these cases was accompanied by
      various developmental ophthalmologic and nonophthalmologic abnormalities. Group 2
      included 26 patients without any significant visual evoked potential or
      electroretinographic alterations, but with overt funduscopic signs of optic nerve
      hypoplasia. These patients were consistently suffering from strabismus and/or
      amblyopia. The visual functions based on visual evoked potential and
      electroretinographic recordings could be fairly normal apart from a pathologic
      ophthalmoscopic picture characteristic of optic nerve hypoplasia. Group 3
      included six patients with abnormal albeit well-recordable visual evoked
      potentials and subnormal or negative-type electroretinograms that suggested an
      accompanying retinal disease. This finding seems to prove that a subset of
      patients with optic nerve hypoplasia with nystagmus may have a primary retinal
      abnormality. Our study provides further evidence that optic nerve hypoplasia is
      not a uniform disease entity.

PMID- 7813378
TI  - The gold foil electrode in pattern electroretinography.
AB  - A recent study found that the gold foil electrode produces large pattern
      electroretinogram amplitudes, but the test-retest reliability was low. In a three
      center study, we observed that 90% of 29 patients who were tested with gold foil
      electrodes used three times appeared to have markedly lower amplitudes than when
      tested with new electrodes during the same session. Across study centers, the
      mean of the new electrode recordings was 3.78 microV (standard deviation, 1.13
      microV), versus 2.93 microV (1.29 microV) for used electrodes. This 0.85-microV
      reduction (22%) was statistically significant (F = 7.10 p = 0.01). Electrodes
      used three times demonstrated an average change in the coefficient of variation
      of 14% (standard deviation/mean = coefficient of variation; new, 1.13/3.78 = 30%;
      used, 1.29/2.93 = 44%). Two of the study sites (Houston/Indianapolis) conducted
      test-retest pattern electroretinograms on a total of 18 patients and found the
      mean evoked potential to be 3.55 microV with new electrodes and 2.82 microV with
      used electrodes. The coefficient of variation for the test-retest data was 30%
      and 47% for new and used electrodes, respectively. Light microscopy showed small
      cracks on the surface of the electrode, with the number and configuration of the
      cracks varying in each electrode. The presence of cracks is further complicated
      by their proximity to the tear film. These sources of variation can result in
      significantly different impedances. We propose that constant flexion, as a result
      of patient blinking, causes cracks in the thin gold surface of the electrode.
      Used electrodes will produce lower pattern electroretinogram amplitudes and poor
      test-retest reliability.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7813379
TI  - Gold foil electrodes: a two-center study of electrode reliability.
AB  - Using the routine techniques employed at our two centers for recording pattern
      electroretinograms and a variety of methods, we investigated the reliability of
      the gold foil electrode over repeated uses. We found no significant difference
      between the pattern electroretinograms recorded with new electrodes and those
      that had had such extensive use in patients that they were believed unsuitable
      for further clinical use. We therefore continue to recommend the gold foil
      electrode for repeated use.

PMID- 7813380
TI  - Influence of simultaneous pattern-reversal electroretinogram recording on visual
      evoked potentials.
AB  - Little is known about the influence of the presence of a gold-foil electrode on
      pattern-reversal visual evoked potential recording, although simultaneous pattern
      reversal electroretinography has been applied in several clinical investigations.
      We compared the results of pattern-reversal visual evoked potentials
      simultaneously recorded with pattern-reversal electroretinograms with those
      obtained during separate pattern-reversal visual evoked potential recording in 10
      normal subjects. Transient response (reversal rate, 1 Hz; check size, 30') and
      steady-state response (reversal rate, 5 Hz; check size, 120', 60', 30', 15' and
      7.5') were analyzed under the stimulus contrast condition of 90%. Neither P100
      latency in transient responses nor amplitudes in steady-state responses exhibited
      significant change at any check size when they were recorded separately or
      simultaneously with pattern-reversal electroretinograms. The results suggest that
      the gold-foil electrode exerts no significant influence on pattern-reversal
      visual evoked potentials. Simultaneous pattern-reversal electroretinogram and
      visual evoked potential recording is therefore confirmed to be a clinically
      useful method. This procedure makes the synchronous recording of both responses
      possible under the identical stimulus conditions.

PMID- 7813381
TI  - Effect of experimental scotoma size and shape on the binocular and monocular
      pattern visual evoked potential.
AB  - A small experimental, central scotoma significantly attenuates the human pattern
      visual evoked potential. The steady-state pattern visual evoked potential was
      recorded from seven visually normal adults who viewed a reversing checkerboard
      with 24' checks and a central scotoma that varied in size and shape. We found
      that square scotomas had to be at least 3 x 3 degrees to significantly (p < 0.05)
      attenuate the pattern visual evoked potential. Receptor density has been shown to
      be greater along the horizontal meridian than the vertical meridian. We
      hypothesized that this results in greater cortical representation of the
      horizontal meridian than the vertical meridian and, therefore, the pattern visual
      evoked potential might be significantly attenuated by a smaller rectangular
      scotoma oriented along the horizontal meridian than along the vertical meridian.
      One dimension of the rectangular scotoma was fixed at either 1 degree or 3
      degrees, while the other dimension was varied from 1 degree to 8 degrees. The
      threshold scotoma size that significantly (p < 0.05) attenuated the pattern
      visual evoked potential was a horizontal scotoma subtending 1 x 4 degrees and a
      vertical scotoma subtending 5 x 1 degree (vertical x horizontal). Meridional
      differences in cortical representation were not apparent to the larger scotoma
      series in which the fixed dimension subtended 3 degrees (3 x 2 degrees and 2 x 3
      degrees). Further analysis of the data revealed that the apparent meridional
      difference for the 1 degree scotoma series was a function of data variability.
      The determinant of the PVEP amplitude was scotoma area, not orientation.
      Monocular and binocular threshold scotoma sizes were the same, which could be due
      to the level of binocular summation demonstrated by our subjects.

PMID- 7813382
TI  - Visual evoked potentials to flash and pattern reversal stimulation after
      administration of systemic or topical scopolamine.
AB  - It has previously been shown that 0.6 mg of scopolamine produces a delay in the
      flash visual evoked potential of young normal volunteers, while the pattern
      reversal response does not change in latency. Recent work has shown that this
      drug differentially affects parvocellular and magnocellular systems. To
      investigate this effect, two studies were performed. In the first study, 0.4 mg
      of scopolamine was injected intramuscularly into 11 young, healthy male
      volunteers who had fasted overnight. The visual evoked potential was recorded to
      both binocular flash stimulation and monocular pattern-reversal stimulation by
      means of a checker-board consisting of 56' checks in a 28 degrees field.
      Responses were recorded before administration of the drug and then 1, 2, 4 and 6
      hours after administration. The scopolamine produced a slowing of the flash P2
      latency of approximately 6 ms (p < 0.05) two hours after drug administration.
      There was no effect on the latency of the flash N2 or pattern-reversal N75 or
      P100. There was an increase in amplitude of the flash N2-P2 component 6 hours
      after drug administration and an increase in the amplitude of the N75 and P100 2,
      4 and 6 hours after the drug. Further subjects were investigated with the use of
      topical administration of 0.125% scopolamine applied monocularly. In all studies
      the other eye acted as a control. The subjects were again young healthy
      volunteers. The visual evoked potential was recorded to both flash and pattern
      reversal stimulation with a checkerboard consisting of 60' checks counterphasing
      at 2 Hz within a 5 degrees field. Results suggest that systemic scopolamine
      affects the tectal pathway but has no peripheral effect.

PMID- 7813384
TI  - Three cone systems under white background in the electroretinogram of the
      cynomolgus monkey.
AB  - We recorded electroretinograms for 31 monochromatic (400-700 nm) full-field
      stimuli at five different adaptation levels from anesthetized cynomolgus monkeys.
      These waveforms were analyzed by means of a principal component analysis to
      discuss the relationship between three cone systems with a white background.
      Under no background, spectral response curves of middle-, long- and short
      wavelength cone showed peaks at 517, 579 and 435 nm, respectively, which are in
      agreement with those of the three cone types. Spectral responses of the middle-
      and long-wavelength cone systems were increased and decreased, respectively, at
      the region of 530-590 nm as the level of white background light increased. These
      opposite changes resulted in the shift of the middle- and long-wavelength cone
      spectral response peaks to 546 and 609 nm, respectively, which suggests
      interaction between long- and middle-wavelength cone systems. The peak of the
      short-wavelength cone system shifted to 452 nm because of decreased responses at
      the region of 400-450 nm. Therefore, the short-wavelength cone system seems to be
      mediated by a different mechanism from that involving long- and middle-wavelength
      cone interaction.

PMID- 7813383
TI  - Early abnormalities of retinal dopamine pathways in rats with hereditary retinal
      dystrophy.
AB  - The dopaminergic pathway that affects rod-driven horizontal cells has been
      studied in the Royal College of Surgeons (RCS) rat during the period preceding
      photoreceptor degeneration (postnatal day 17-24). The experiments were performed
      by intracellular recording from single horizontal cells in vitro. Horizontal
      cells from the recessive control animals (postnatal day 17-24) were depolarized
      by dopamine (10 microM) and hyperpolarized by the D1 antagonist SCH 23,390 (10
      microM). In contrast, cells from age-matched dystrophic retinas, though
      depolarized by dopamine, were unaffected by SCH 23390 (10-100 microM), suggesting
      a significant reduction in the level of endogenous dopamine release. Histologic
      examination for catecholaminergic neurons revealed no differences in either the
      cell number or anatomy between the retinas of the control and dystrophic animals.
      Furthermore, perfusion of the control retinas with melatonin (500 nM-1 microM)
      yielded response characteristic of the dystrophic type. In the period preceding
      degeneration, the RCS retina thus displays a discrete abnormality in dopaminergic
      pathways, such that there is a gross reduction in endogenous dopamine release
      below that required to activate D1 receptors. Since melatonin levels have been
      shown to be high in these retinas, we propose that abnormalities in the dopamine
      melatonin systems give rise to an electrophysiologic deficit in the
      postphotoreceptoral retina of the RCS rat.

PMID- 7813385
TI  - An in vitro characterization of cefditoren, a new oral cephalosporin.
AB  - Cefditoren (ME 1206) is a new cephalosporin available for oral administration as
      the pivaloyloxymethyl ester (ME 1207). The effect of medium formulation. pH,
      cation concentration and inoculum on the in vitro activity of cefditoren was
      investigated prior to determining its comparative antibacterial potency against a
      wide range of clinical bacterial isolates, its bactericidal activity against
      susceptible strains and the duration of its post-antibiotic effect (PAE).
      Cefditoren was shown to possess a broad-spectrum of cidal antibacterial activity
      against both Gram-positive and Gram-negative species with stability to many beta
      lactamases of clinical importance. Its activity against Gram-positive species was
      similar to augmentin and cefuroxime, but superior to that of cefaclor and
      cefixime, while its beta-lactamase stability was similar to that of cefixime and
      ceftazidine, characterizing it as a third generation cephalosporin. Investigation
      of the effect of laboratory variables on the in vitro activity of cefditoren
      indicates that it will present no special problems when tested in the clinical
      setting against bacterial pathogens. PAE of 0.9 h, or greater, for Staphylococcus
      spp, Streptococcus pneumoniae and Moraxella catarrhalis may support the use of an
      extended dose-interval when cefditoren is used for the treatment of respiratory
      tract infections.

PMID- 7813386
TI  - An experimental model to reproduce some bacterial intestinal cocultures in germ
      free mice.
AB  - The objective of this study was to create a stable experimental model to act as a
      living incubator for the main important intestinal bacteria. We have therefore
      inoculated germ-free mice with the most important bacteria of the human
      intestinal microflora, in order to study the effect of some oral antibiotics on
      the intestinal microflora. Sixty germ-free mice, 7 weeks old and of either sex,
      were inoculated orally with human faecal bacteria by means of their drinking
      water. Administrations were made at regular intervals following a scheme that
      respected some of the metabolic inter-relationships of the microorganisms used.
      The results showed that colonization of the germ-free mouse intestines had been
      achieved by most of the bacteria that had been inoculated. This "coculture" was
      stable in time, contrary to what happens when in-toto lyophilized faeces are
      administered, and the bacterial concentrations for each strains were similar to
      those found in human faeces.

PMID- 7813387
TI  - Comparison of cardiotoxicity of pirarubicin, epirubicin and doxorubicin in the
      rat.
AB  - The authors have examined the cardiotoxic actions of pirarubicin (THP), compared
      with epirubicin (EPI) and doxorubicin (DXR), on the electrocardiogram (ECG) and
      myocardial structure in rats. The rats were treated once a week for four weeks
      with DXR (total dose 10 mg/kg), and then further treated (post-treated) once a
      week for four weeks with THP, EPI or DXR (total dose 5 and 10 mg/kg). In the ECG
      study, a prolongation of QaT interval (interval from the upstroke of R wave to
      the apex of T wave) and a flattening of T wave were observed more severely in the
      rats post-treated with EPI and DXR than in those treated with THP. Also, a
      prolongation of QRS duration was observed more prominently in those treated with
      DXR than with THP and EPI. Histopathologically, a vacuolization and swelling of
      myocardial cells and an infiltration of mononuclear cells were observed more
      severely in the rats post-treated with EPI and DXR than in those treated with
      THP. Furthermore, a meandering of myofibril was observed in those treated with
      EPI and DXR, but not with THP. These results suggest that the cardiotoxic actions
      of THP are weaker than those of EPI and DXR and that the replacement of DXR with
      THP leads to more successful cancer chemotherapy with less cardiotoxicity.

PMID- 7813389
TI  - L-acetylcarnitine treatment of mental decline in the elderly.
AB  - A single-blind clinical trial was carried out on 481 subjects enrolled in 44
      geriatric and neurologic units following a strict selection criteria: age, Mini
      Mental State Examination (MMSE) Global Deterioration Scale and Geriatric
      Depression Scale (GDS). After the initial screening and enrollment, the trial was
      run for 150 days in four phases: phase T0 (placebo treatment for 30 days), phases
      T1 and T2 (L-acetylcarnitine (LAC) 1500 mg/day for 90 days), phase T3 (further 30
      days of placebo treatment). Drug efficacy was evaluated according to changes
      occurring from the beginning to the end of the tests which evaluate either whole
      and specific cognitive performances, or emotional-affective and relational
      behaviour. The outcome of phase T3 enabled the authors to estimate the possible
      favourable effects persisting after termination of L-acetylcarnitine therapy. The
      cognitive sphere evaluated by MMSE showed a significant increase in the total
      score at the end of LAC treatment (p < 0.0001). The Randt Memory Test also
      revealed that LAC treatment improved the items tested: the total score and the
      memory index increased significantly and the favourable effect persisted after
      LAC was discontinued. The emotional-affective area showed a significant
      improvement in the total score of the GDS after LAC therapy, and the positive
      results were confirmed by the Hamilton Rating Scale (p < 0.0001). The behavioural
      relational aspects evaluated by the Family Stress Scale showed a significant
      decrease in the total score after treatment (p < 0.0004); the same trend was
      observed in the scores for instability and negative feeling. No significant
      adverse drug reaction occurred during the trial. In conclusion, the statistical
      analysis of the data from this single-blind, multicentre trial of mild mental
      impairment in the elderly showed a significant improvement of several
      performances during and after LAC treatment. Other reports indicate that this
      drug may be effective in the treatment of dementia.

PMID- 7813388
TI  - The influence of antineoplaston A5 on the central dopaminergic structures.
AB  - Antineoplastons are naturally occurring cytodifferentiating agents. Chemically,
      antineoplastons are medium and small sized peptides, amino acid derivatives and
      organic acids which exist in blood, tissues and urine. In clinical trials in
      advanced cancer, in addition to the anticancer activity it was observed that
      patients suffering from both cancer and Parkinson's disease exhibited marked
      improvement in parkinsonian symtomatology when treated with antineoplaston A5.
      The present study was designed to analyse the influence of A5 on central
      dopaminergic structures. Mice and rats were given A5 intraperitoneally at three
      different dosage levels. Experiments conducted included spontaneous locomotor
      activity, amphetamine-induced yawning and erections, catalepsy, the effect on the
      level and utilization of noradrenaline and dopamine in the brain and the
      influence of prolonged and chronic treatment on the haloperidol-induced
      catalepsy. It has been demonstrated that A5 stimulates the central dopaminergic
      receptors. It diminishes the cataleptic response to haloperidol and enhances the
      incidence of apomorphine-induced yawning. Biochemical studies demonstrated
      increased concentration of dopamine and noradrenaline in the brain and diminished
      utilization of both catecholamines.

PMID- 7813390
TI  - Screening of a mouse/human Y-chromosomal cosmid library for gene candidates and
      markers by using (short) oligonucleotide probes.
AB  - A comprehensive approach is described for the identification of sequences of
      interest from a human Y chromosomal cosmid library via (short) consensus
      oligonucleotide probes. It involves the ordering of cosmid clones grown in
      microtiter plates onto small filter membranes by a robot workstation. A high
      number of the clones are characterized by their repetitive sequence content,
      either by ubiquitously interspersed simple tandem blocks or by Y-specific
      elements. The Y chromosomal repeat (DYZ2) appears underrepresented in the
      library. In contrast many novel microsatellite marker systems can now be
      developed for the Y chromosome on the basis of the simple repeat blocks described
      here. Though novel genes were not yet delineated so far, a number of candidate
      sequences with high coding potential and other interesting characteristics are
      described.

PMID- 7813391
TI  - A polymerase chain reaction-based method for the identification of DNA samples
      from common vertebrate species.
AB  - Polymerase chain reaction (PCR) amplification of vertebrate genomic DNAs using a
      (CAC)n primer was found to generate species-specific patterns which are
      resolvable by agarose gel electrophoresis. Of the thirteen species tested (trout,
      frog, chicken, mouse, rat, cow, dog, African green monkey, chimpanzee, orangutan,
      gorilla, rhesus macaque, and human), all species showed discrete amplification
      products ranging in size from 1.0 to 3.2 kbp although trout and frogs had only
      weak (CAC)n amplification products. Most species had three to six bands except
      rodents, who had eight bands, and cows, who had a single band at 2.2 kbp.
      Importantly, within a single species, different unrelated individuals had highly
      similar amplification band patterns although the relative intensities of the
      bands varied. This held true even when different unrelated humans of different
      racial backgrounds were tested. We conclude that this technique is potentially
      useful for identifying which vertebrate species contributed DNA to a given
      biological sample (e.g., bloodstains, semen, hair) and that only a very small
      amount of sample is necessary for the analysis.

PMID- 7813392
TI  - A computer simulation accounting for dissimilar electrophoretic behavior between
      two similarly curved DNA fragments due to a difference in arc-length.
AB  - Arc-shaped bent DNA fragments of the same predicted planar curvature but
      differing in length by 20% were compared in regard to their mobilities in 3 to
      10% polyacrylamide. The longer (155 bp) fragment is retarded far more severely
      than the shorter (124 bp) fragment. The effect of gel concentration in promoting
      the retardation is far more pronounced for the 155 bp than for the 124 bp
      fragment. Moreover, a temperature change from 25 degrees C to 4 degrees C does
      not substantially affect the gel concentration dependent mobility of the 124 bp
      fragment while it increases the retardation of the 155 bp fragment greatly. The
      strong increase in retardation brought about by a mere 20% increase in the length
      of the arc was accounted for by a simple computer simulation of gel
      electrophoresis which considered the rate of passage of arc-shaped objects
      through a two-dimensional array of disc-shaped obstacles. Since the simulation
      relies exclusively on geometric factors, its success in predicting the behavior
      of the 124 and 155 bp DNA fragments suggests that geometric factors are largely
      responsible for their electrophoretic properties. The simulation can account for
      the strong temperature effect on the retardation of a model of the 155 bp DNA in
      polyacrylamide gels by showing that a decreased degree of random motion has a
      profound effect on the modeled 155 bp particle, but not on the modeled 124 bp
      DNA.

PMID- 7813393
TI  - Fluorescent-based typing of the two short tandem repeat loci HUMTH01 and
      HUMACTBP2: reproducibility of size measurements and genetic variation in the
      Swedish population.
AB  - The aim of this study was to investigate the reproducibility of genetic typing of
      two tetrameric short tandem repeat (STR) loci and the extent of genetic variation
      in the Swedish population. An automated, fluorescent-based Applied Biosystems
      373A sequencer was used for typing of the HUMTH01 and HUMACTBP2 loci (also named
      SE33). The former locus has seven alleles in the size range of 154-174 bp, while
      the latter is a complex locus with more than 32 alleles in the range of 227-316
      bp. Using different fluorescent dyes, polymerase chain reaction (PCR) products
      from the two STR loci were sized in one lane using an internal size standard. In
      order to compare within- and between-gel reproducibility of fragment size
      estimates, a control sample was typed three times on each of 20 gels. Within the
      gel, the standard deviation (SD) of fragment size variability was less than 0.1
      bp for four fragment sizes between 158-291 bp. Standard deviations between gels
      were slightly higher for the two shorter fragment sizes (HUMTH01), while the
      larger fragments varied between 0.3 and 0.4 bp (HUMACTBP2). The amount of genetic
      variation was investigated in samples from three Swedish cities (n = 301). Seven
      alleles were found at HUMTH01 and the observed heterozygosity was 0.77. At the
      HUMACTBP2 locus more than thirty alleles were found and the observed
      heterozygosity was 0.96. The observed genotype frequencies at HUMTH01 and
      HUMACTBP2 did not deviate significantly from Hardy-Weinberg expectations. No
      indication of a significant excess of homozygotes was found at any of the loci.
      We conclude that both HUMTH01 and HUMACTBP2 can be reliably typed using the
      method described. However, the latter locus requires an allelic ladder to be run
      on each gel.

PMID- 7813394
TI  - The use of polyacrylamide gel electrophoresis for the analysis of acidic glycans
      labeled with the fluorophore 2-aminoacridone.
AB  - A method is described for the electrophoretic analysis of fluorophore-labeled
      acidic glycans. Various glycoproteins were treated with the enzyme, peptide N
      glycosidase F, to release mixtures of asparagine-linked glycans that were then
      labeled with the fluorophore 2-aminoacridone, and the resulting derivatives
      electrophoresed in high-density polyacrylamide gels. The acidic glycans were
      separated with high resolution and distinct, well-resolved fluorescent band
      patterns were produced. Neutral saccharides did not electrophorese in the system.
      Information on the structure of the glycans was revealed by the changes in the
      band patterns observed after the mixtures of the glycan fluorophore derivatives
      were treated with either of the enzymes neuraminidase or beta-galactosidase.
      Quantities of glycoprotein as little as 10 micrograms were analysed without
      difficulty. The electrofluorograms were viewed using a digital imaging system
      based on a cooled charge-coupled device. The method was also demonstrated using
      purified acidic glycans of known structure. The method was easy to use, enabled
      the sensitive analysis of multiple samples in parallel and should be a useful
      addition to the range of glycan analytical techniques.

PMID- 7813395
TI  - Detection of lectin activity on western blots using erythrocytes.
AB  - A method is described for the direct detection of lectins, agglutinating
      erythrocytes, on nitrocellulose membranes after Western blotting, thus avoiding
      protein extraction from specific bands in the gel, followed by agglutination
      assays. The methodology essentially involves exposing the lectin band on a
      nitrocellulose strip to trypsinized rabbit erythrocytes (2%, in 0.15 M NaCl) for
      30 min at 37 degrees C and then carefully transferring the membrane to saline (4
      degrees C) for a few gentle washes and then fixing it in a solution (0.2%
      glutaraldehyde in 0.15 M NaCl) for 30 min. Later, the membrane is gently washed
      several times in 0.15 M NaCl containing 10 mM beta-alanine. The lectin band is
      visualized as a red agglutinated patch. The method is specific for lectins that
      can agglutinate red blood cells and virtually has no cross reactivity with the
      various nonlectin proteins tested. Binding of erythrocytes to the lectin band on
      the nitrocellulose strip can be prevented by specific competing sugars. The
      method can be applied to screen for the presence of lectins in natural materials
      and to monitor lectin fractions during purification.

PMID- 7813396
TI  - Pulsed-field gel electrophoresis for the separation of large protein molecules
      exemplified by the isoforms of apolipoprotein (a).
AB  - The performance of pulsed-field gel electrophoresis (PFGE) was assessed for the
      separation of protein molecules. The allelic isoforms of apolipoprotein (a)
      (apo[a]) served as a model for this study because apo(a) is an unusually large
      protein, consisting of a variable number of repeating units. PFGE and, for
      comparison, conventional electrophoresis of human sera were carried out under
      reducing conditions in agarose gel. After blotting proteins onto nitrocellulose
      membrane, a combination of monospecific rabbit anti-apo(a) antibody and alkaline
      phosphatase-conjugated protein A detected apo(a) isoforms in all sera tested. The
      various apo(a) isoforms were effectively resolved within two repeating units
      ("kringles") by both PFGE and conventional electrophoresis, but the type of
      agarose gel used greatly affected the speed of electrophoretic separation. In a
      series of 89 human sera, 59 double-band and 30 single-band patterns were seen
      using either electrophoretic system. However, one specimen produced double bands
      with PFGE, while only a single band could be detected by conventional
      electrophoresis, and with another specimen the opposite occurred. A total of 22
      different apo(a) isoforms were identified among these patterns. It is concluded
      that the increasingly available PFGE technology is a practical alternative to
      conventional agarose electrophoresis for the separation of large protein
      molecules.

PMID- 7813397
TI  - Method for rapid electrophoretic transfer of isoelectric focusing gels to
      polyvinylidene difluoride.
AB  - We present here a protocol for unidirectional wet electrotransfer of isoelectric
      focusing (IEF) gels to polyvinylidene difluoride (PVDF) that can be carried out
      in < 2 h, including preequilibration steps. In developing this protocol, we
      systematically evaluated sodium dodecyl sulfate and methanol concentrations in
      the preequilibration washes and length of electrotransfer. We demonstrated that
      the method is useful for tubulin, a protein that resists usual semi-dry transfer
      procedures due to its limited solubility under IEF conditions. We also
      successfully used our method for transferring the microtubule-associated protein,
      tau, as well as carbamylyte standards, creatine phosphokinase and carbonic
      anhydrase.

PMID- 7813398
TI  - On the use of dimensionless parameters in acid-base theory. VII. The pH of
      solutions of salts of a strong acid and a weak base or vice versa.
AB  - The equation for the hydrogen ion activity in solutions of salts of a strong acid
      and a weak base, or vice versa, is of the third degree. Nevertheless, explicit
      equations for pH of such solutions can be formulated as linear functions of the
      logarithm of the salt concentration. The equations are valid within the major
      parts of pH and concentration intervals of experimental interest. The ranges of
      validity are given in terms of mathematically defined pH intervals. Close
      relations with pH of free base or free acid solutions of the same concentration
      as the salt are demonstrated. For instance, the pH difference between solutions
      of the salt and the free base or acid having unit activities is +/- 7 pH units.

PMID- 7813399
TI  - Quantitative analysis of hyaluronan in vitreous humor using capillary
      electrophoresis.
AB  - Capillary electrophoresis was used for the separation and quantitative analysis
      of the glycosaminoglycan hyaluronan in human and bovine vitreous with detection
      by UV absorbance at 200 nm. Calibration was carried out using standards made up
      from known concentrations of hyaluronan of umbilical cord origin. The purity of
      the standard was examined by 1H NMR (nuclear magnetic resonance). Concentrations
      as low as 25 micrograms/mL could be detected by capillary electrophoresis.
      Confirmation that the signal was due to hyaluronan was obtained by
      depolymerization of the native mucopolysaccharide by hyaluronidase. This resulted
      in loss of the hyaluronan peak and appearance of several new peaks corresponding
      to the oligomeric fragments which had shorter migration times. Capillary
      electrophoresis is a reproducible and sensitive technique for the quantification
      and characterisation of hyaluronan in vitreous samples.

PMID- 7813400
TI  - Capillary zone electrophoresis and micellar electrokinetic chromatography of 4
      aminobenzonitrile carbohydrate derivatives.
AB  - Aldoses, ketoses and uronic acids were derivatized successfully within 15 min at
      a temperature of 90 degrees C by reductive amination with 4-aminobenzonitrile.
      Subsequently, the derivatives were separated as their borate complexes by
      capillary zone electrophoresis, using 175 mM borate buffer, pH 10.5, as carrier.
      The electrophoretic mobilities were determined by the complex stability, which
      was found to depend on the number of hydroxyl groups on any given carbohydrate
      derivative, the presence of substituents, and most strongly on the configuration
      of the vicinal hydroxyl groups at C-3 and C-4 in aldoses and uronic acids, and
      with regard to ketoses on those at C-4 and C-5. Time of analysis could be reduced
      considerably by the use of micellar electrokinetic chromatography, which
      separated 4-aminobenzonitrile sugar derivatives on the basis of their
      differential partitioning into an electroendosmotically driven aqueous phase and
      into sodium dodecyl sulfate micelles. Optimum resolution was achieved with a Tris
      phosphate buffer, pH 7.5, containing 100 mM of sodium dodecyl sulfate. The method
      made it possible to resolve several carbohydrates which had not been resolved
      successfully by means of capillary zone electrophoresis, such as glucose and
      fructose. Moreover, separation selectivity could be adjusted by varying the
      capillary temperature. Finally, on-column UV monitoring at 285 nm allowed the
      detection of glucose with a lower mass detection limit of 1 fmol and a
      concentration sensitivity of 0.3 microM.

PMID- 7813401
TI  - Preparative isoelectric focusing in multicompartment electrolyzers: novel,
      hydrolytically stable and hydrophilic isoelectric membranes.
AB  - Preparative isoelectric focusing in multicompartment electrolyzers is based on
      the production of isoelectric membranes of precise isoelectric point, able to
      buffer at their pI value and to titrate proteins tangent to or crossing the
      membranes. Up to the present, such membranes have been based on polyacrylamide
      chemistry; acrylamide, however, is neither stable in acidic nor basic
      environments. We describe here novel membranes, produced with a unique monomer, N
      acryloylaminoethoxyethanol (AAEE). Poly(AAEE) membranes are extremely stable to
      alkaline hydrolysis (500 times more stable than polyacrylamide) and even more
      hydrophilic than the latter matrix. This allows production of highly reproducible
      membranes (these do not change their pI with time, since no acrylic acid is
      produced by hydrolysis upon storage) which do not adsorb proteins by hydrophobic
      interaction.

PMID- 7813404
TI  - Immobilised pH gradient isoelectric focusing of wool proteins.
AB  - Conventional carrier ampholyte-isoelectric focusing is unsuitable for separating
      wool and hair proteins. The inability to form stable narrow pH gradients at
      acidic pH values does not allow good resolution of the many acidic wool and hair
      proteins. To evaluate the usefulness of immobilised pH gradient-isoelectric
      focusing (IPG-IEF) for wool proteins, S-amidomethyl wool proteins were analysed
      using IPG-IEF. Over twenty bands were visible on a pH 4-7 IPG-IEF gel. IPG-IEF
      was combined with sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS
      PAGE) to give a two dimensional separation, and over 50 protein spots were
      observed. IPG-IEF appears to be ideally suited to the separation of wool
      proteins. The resolution of two-dimensional electrophoresis using IPG-IEF was
      greater than previously obtained using acid or alkaline PAGE in the first
      dimension. Good reproducibility of spot position was observed.

PMID- 7813402
TI  - Differentiation by preparative continuous free flow-isoelectric focusing of
      cyclosporin A inhibitable peptidyl-prolyl cis/trans isomerase of human
      erythrocytes.
AB  - Preparative continuous free flow-isoelectric focusing has been used to separate
      at least three different components of intrinsic peptidyl-prolyl cis/trans
      isomerase (PPIase) activity from erythrocytes lysate. By adding chemical spacer
      molecules like glycine and Bicine to commercial carrier ampholyte mixtures the
      resulting pH profile was predictably influenced. With an applied field strength
      of 125-170 V/cm a residence time of less than 15 min was sufficient for the
      separation of PPIases with isoelectric points of 5.4, 5.7 and 5.9 from the bulky
      hemoglobin. The recovery of the overall PPIase activities was about 100%. The
      purification factor has been determined as 20- to 100-fold. For each isoform of
      the enzyme the peptidyl-prolyl cis/trans isomerase activity of the separated
      proteins was inhibited by cyclosporin A but was resistant toward FK 506.

PMID- 7813403
TI  - Multifunctional apparatus for electrokinetic processing of proteins.
AB  - New equipment (the "Gradiflow") has been designed and constructed to provide
      efficient large-scale preparative fractionation of macromolecules, based on
      charge and/or size differences, as well as the concentration of macromolecules
      and electrodialysis. Examples of its capability are the separation of a mixture
      of haemoglobin (50 mg) from bovine serum albumin (50 mg) within 15 min (based on
      charge differences at pH 6.8), the purification of phycoerythrin from a crude
      extract on the basis of size, and the fractionation of serum proteins into two
      discrete size classes.

PMID- 7813405
TI  - Data management in a two-dimensional gel electrophoresis laboratory: "gelscript
      1" software.
AB  - We have developed a software package "gelscript 1", to perform data operations in
      a laboratory that runs and analyzes a large number of two-dimensional (2-D) gels.
      This system is managed automatically by the "4th Dimension" relational database
      on a Macintosh platform. A guiding principle in the development of "gelscript 1"
      was that any piece of information is entered into the system only once, and is
      retrieved, copied, inserted or checked whenever required. In addition to saving
      labor, this principle ensures consistency and integrity of the database. The
      system always "knows" how many gels were run from any one sample, how long the
      films were exposed or were supposed to be exposed. It keeps track of data
      throughout all operations, warns of improper sample assignments, and prints
      labels for films, samples, protocols, etc. The software can be adapted to other
      applications, in which many samples are processed and where cross-referencing is
      needed.

PMID- 7813406
TI  - Detection of thymopoietin-responsive proteins in nude mouse spleen cells by two
      dimensional polyacrylamide gel electrophoresis and image processing.
AB  - Lymphoid cells isolated from the spleen of BALB/c nu/nu nude mice were treated
      with synthetic human thymopoietin, and newly synthesized proteins were labeled by
      [35S]methionine incorporation. In the control experiment, the same lot of spleen
      cells were incubated in the labeling medium without the addition of thymopoietin.
      Urea/detergent-soluble proteins were extracted from the cells after 3 h
      incubation to be separated by two-dimensional poly-acrylamide gel
      electrophoresis. Spots of [35S]methionine-labeled proteins were visualized by
      autoradiography and analyzed by image processing. The computer-aided spot
      matching screened out three major thymopoietin-responsive proteins, TRP-1, -2 and
      -3. [35S]Methionine incorporation into TRP-3, of which the isoelectric point and
      molecular mass were approximately pI 5 and 10 kDa, respectively, was decreased by
      the thymopoietin treatment. In contrast with the down regulation, TRP-1, which
      was slightly higher in pI and slightly larger in molecular mass, and TRP-2, which
      was slightly higher in pI and almost the same in molecular mass as TRP-3, were
      evidently induced by the treatment. However, TRPs could not be assigned to Thy-1
      antigen on the difference in molecular mass. The specific induction by the
      thymopoietin treatment suggested that TRP-1 and -2 might be novel proteins
      related to the intracellular signal transduction.

PMID- 7813407
TI  - Analysis on heterogeneity of squamous cell carcinoma antigen by two-dimensional
      electrophoresis.
AB  - Squamous cell carcinoma (SCC) antigen was separated by two-dimensional
      electrophoresis combined with immunoblotting into four spots: spot 1 with pI 6.4
      and 44.5 kDa, spot 2 with pI 6.3 and 44.5 kDa, spot 3 with pI 6.0 and 44.5 kDa,
      and spot 4 with pI 5.9 and 45 kDa. In cancer and noncancerous tissues, it was
      common that spot 1 was the largest spot. In noncancerous tissues, spot 3 was the
      smallest spot and spot 2 was stained as densely as spot 4. In cancer tissues,
      however, spot 4 was apparently smaller than spot 2 and 3. Also, spots 2 and 3 in
      cancer tissues were larger than those in noncancerous tissues. When SCC antigen
      was treated with alkaline phosphatase prior to isoelectric focusing (IEF), spot 4
      disappeared from the immunoblotting pattern. When the SCC antigen was treated
      with alkaline phosphatase after IEF, spot 4 changed its molecular weight to the
      same weight as that of the other three spots. These results strongly suggest that
      spot 4 is phosphorylated SCC antigen.

PMID- 7813408
TI  - Comparison of protein analysis between embryonic and extraembryonic tissues
      during the 11th day of gestation of the mouse.
AB  - At day 11 of gestation, embryos and their extraembryonic tissues were isolated
      from the uterus of Him OF1/SPF mice and incubated in Dulbecco's modified Eagle's
      medium (DMEM) containing L-[35S]methionine. After 4 h of incubation, the embryos
      were dissected to obtain the heart, liver, limb buds, and brain. The latter was
      fragmented into the telencephalon, mesencephalon, and myelencephalon. These
      organs and the extraembryonic tissues such as chorion, yolk sac, and placenta
      were processed for two-dimensional (2-D) gel electrophoresis. About 1000 proteins
      with relative molecular weights (M(r) varying from 10,000 to 200,000 and
      isoelectric points ranging from 4 to 10 could be detected on these gels. The
      protein patterns of the various organs and tissues were analyzed for organ- and
      cell lineage-specific protein spots. We detected subtle differences in the
      protein patterns of the three cerebral areas when compared to each other. In
      addition, we found protein spots characteristic for the entire brain. We also
      found several heart-specific protein spots. Distinct protein synthesis was also
      detected in liver and limb buds. Several groups of protein spots seem to be
      differentially regulated in these organs. Substantial differences between the
      patterns of embryonic and extraembryonic tissues were observed. In addition,
      several clusters of protein spots of well-defined molecular weight could be
      detected only in extraembryonic tissues. We propose that organ- and tissue
      specific differences in protein synthesis are linked to some of the morphogenetic
      and functional processes during mammalian embryogenesis. Identification of
      particular proteins will serve as a basis to search for the corresponding genes.

PMID- 7813409
TI  - Transitory and short-duration changes of sleep organization provoked by
      amygdaloid kindling in the cat: a daily 23-hour sleep recording study.
AB  - The effect of amygdaloid kindling on sleep organization was tested in chronically
      implanted cats on a 12:12 light-dark cycle. Electrical kindling stimuli were
      delivered to the amygdala every 2 h during the light period. Total sleep time and
      percentage, mean duration, and mean number, as well as the hourly accumulation of
      waking (W) and sleep (slow wave sleep I and II, and paradoxical sleep) episodes
      were assessed from daily 23-h sleep recordings, consisting of baseline control
      recordings, control recordings where cats were briefly alerted at 2-h intervals
      to mimic the kindling trials manipulation, and recordings on each kindling day.
      The kindling process was completed within six days achieving three to five
      consecutive fully kindled seizures. Analysis of total recording time showed that
      the kindling process enhanced W stage and diminished total sleep time only on the
      second kindling day. Analysis of light and dark periods demonstrated compensatory
      W and sleep changes during the dark periods. Hourly sleep stage time accumulation
      was slowed during kindling trials, but compensated while stimuli were suspended.
      All of these changes returned to baseline values at the end of kindling. No
      significant differences between changes induced by kindling and those produced by
      alerting trials were found. We conclude that sleep alterations can not be
      exclusively attributed to kindling development, and that sleep is able to become
      adapted to the focal and generalized seizures effect.

PMID- 7813410
TI  - A new, non-pharmacologic model of convulsive status epilepticus induced by
      electrical stimulation: behavioral/electroencephalographic observations and
      response to phenytoin and phenobarbital.
AB  - Much remains to be learned about mechanisms underlying entry into, and temporal
      progression of, status epilepticus (SE). This report describes a non
      pharmacologic model of generalized convulsive SE in rat. Pulsed trains of
      suprathreshold electric current, were administered bilaterally to either of four
      rostral forebrain sites: orbital cortex, medial precentral cortex, deep
      prepiriform cortex, or rostral caudate-putamen (n = 8 per site). This induction
      method resulted in 30/32 animals attaining limb-clonic convulsive SE within a
      mean of 30-35 min for each forebrain site, with no differences between sites.
      Subsequent SE proceeded without further interventions, permitting observation of
      the natural course of progression. A stereotyped behavioral/electrographic
      sequence occurred, characterized by devolution. Behaviorally, animals progressed
      from predominantly limb clonus to head clonus, then to subtle twitching, and
      finally to electrical SE before cessation of spikes. The corresponding
      electrographic progression was from fast and slow spiking to periodic
      epileptiform discharges (PEDs). In 20 animals surviving to 48 h, pathologic
      damage affected mainly limbic sites; damage was related to total convulsive time
      rather than to clonic activity. High-dose phenobarbital but not phenytoin
      suppressed SE when given during orbital cortex-induced limb-clonic SE. These
      findings are compatible with human observations and indicate that this model will
      enable investigations of generalized SE mechanisms and evaluation of new
      therapeutic agents for refractory SE.

PMID- 7813411
TI  - Hippocampal epileptogenesis produced by electrolytic iron deposition in the rat
      dentate gyrus.
AB  - Anodal current passed through a stainless-steel electrode, positioned
      unilaterally in the rat dentate gyrus hilus, will produce recurrent motor
      seizures and significant changes in the neuronal expression of several messenger
      RNAs (mRNAs) throughout the full bilateral extent of the hippocampus. The present
      study quantitatively analyzed electroencephalograms (EEGs) from rats receiving
      this electrolytic treatment in order to characterize the resultant hippocampal
      seizure activity. To examine the epileptogenic role of ferric ion deposition to
      that of current-induced tissue destruction, we compared steel to platinum
      electrodes. Adult male rats were surgically implanted with a chronic recording
      electrode in the CA3 region of the hippocampus, and then (contralaterally) with
      either an insulated steel electrode in the hilus, platinum electrode in the
      hilus, or steel electrode in the medial entorhinal cortex. Each rat received an
      anodal current through the nonrecording treatment electrode while connected to a
      polygraph. Currents ranged from 0.8 mA, 7 s for hilus electrodes to 2.0 mA, 20 s
      for entorhinal cortex electrodes. EEGs were collected from alert, unrestrained
      rats for up to 50 consecutive hours, and additional EEGs were recorded
      periodically over a 4-day period. Subjects were sacrificed and brain sections
      were microscopically examined for evidence of neuropathology. The results
      demonstrate that electrolytic deposition of iron ions in the hilus, and not
      merely hilus tissue destruction, produce electrographic seizure activity within 1
      2 h of current passage. Seizures recurred most intensely for 2-3 h, and sporadic
      epileptiform activity was detected for up to 12 h. Motor seizures of class 4 or 5
      were observed in all seizing rats, and were always coincident with hippocampal
      seizure discharges. Histological examination of brain sections from all subjects
      found no evidence of cell death in the contralateral hippocampus. The dentate
      gyrus appeared to be the most epileptogenic site tested because hippocampal iron
      deposition that did not include the dentate gyrus, or iron deposition in the
      entorhinal cortex, was significantly less epileptogenic.

PMID- 7813412
TI  - Cognitive side-effects of phenytoin compared with carbamazepine in patients with
      localization-related epilepsy.
AB  - In continuation of an earlier study of our group (Neurology, 43 (1) (1993) 41
      51), we present the results of an investigation of the adverse effects of
      carbamazepine versus phenytoin on cognitive function. Two groups of twenty-five
      patients are compared in an open, parallel group and non-randomized clinical
      investigation: a group of patients on carbamazepine (CBZ) monotherapy versus a
      group of similar size on phenytoin (PHT) monotherapy. The two groups do not show
      significant differences on variables that could confound the comparison of drug
      specific adverse effects: age, gender, intelligence, type of epilepsy, seizure
      type, seizure frequency, EEG focus and age at onset of the epilepsy. All patients
      were investigated with a comprehensive neuropsychological test battery ('FePsy'),
      assessing the cognitive domains of 'speed factors', memory and attention. The
      results show lower performance in the PHT group compared to the CBZ group on all
      tests measuring motor speed. Additionally, there is evidence that PHT also
      affects the speed of central 'higher cortical' processing systems. Our
      investigation also shows slower performance in tasks that measure speed of
      information processing ('mental speed'). The other investigated areas, i.e. short
      term memory, long-term (verbal and non-verbal) memory and selective attention, do
      not reveal statistically significant differences between the two groups. These
      results reconfirm that patients on PHT may suffer from cognitive side-effects
      even when the medication is sufficiently controlled and the drugs are given
      within the assumed therapeutical interval.

PMID- 7813413
TI  - Effects of GABAA receptors activation on brain glucose metabolism in normal
      subjects and temporal lobe epilepsy (TLE) patients. A positron emission
      tomography (PET) study. Part I: Brain glucose metabolism is increased after GABAA
      receptors activation.
AB  - Though gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in
      the human central nervous system, the metabolic response to GABA system
      activation remains imperfectly known. We studied in vivo with positron emission
      tomography (PET) the variations of glucose metabolism in the human brain after
      stimulation of the GABAA receptors by systemic administration of the specific
      GABAA agonist, 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP). These
      investigations were performed in three normal volunteers and as part of
      presurgical evaluation for temporal lobe epilepsy in six patients. While clinical
      and electroencephalographic (EEG) monitoring showed a sedative effect and
      sleepiness after THIP administration, glucose metabolism was paradoxically
      increased in grey matter structures, which are known to have a high density of
      GABAA receptors. These findings suggest that the pharmacological activation of
      GABA pathways, although inhibitory and producing a decrease of vigilance,
      increases the energetic demand at least during a phase of GABA agonist action,
      probably at the synaptic or at the glial cell level.

PMID- 7813414
TI  - Effects of GABAA receptors activation on brain glucose metabolism in normal
      subjects and temporal lobe epilepsy (TLE) patients. A positron emission
      tomography (PET) study. Part II: The focal hypometabolism is reactive to GABAA
      agonist administration in TLE.
AB  - Positron emission tomography (PET) using [18F]fluorodeoxyglucose (FDG) was used
      to study the metabolic response of focal hypometabolism to the administration of
      a specific GABAA agonist (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol), THIP,
      in six temporal lobe epilepsy (TLE) patients. After THIP injection, the increase
      of glucose metabolism in the hypometabolic focus was larger than the mean
      increase reported in the whole brain (Part I; Epilepsy Res., 19 (1994) 45-54).
      Within the hypometabolic focus, this increase was significantly higher in regions
      with the lowest basal metabolic level. This metabolic response in the
      hypometabolic focus, observed in the absence of any epileptic discharge during
      FDG accumulation and PET data acquisition, suggests that GABAA receptors are up
      regulated or, at least, preserved in TLE.

PMID- 7813415
TI  - The effects of brain lesions on the course of chronic epilepsies.
AB  - The effect of intercurrent brain lesions on the characteristics of chronic
      epilepsies has not yet been the subject of detailed investigation. We therefore
      retrospectively examined this issue for idiopathic, cryptogenic as well as
      symptomatic chronic epilepsies in patients documented in routine investigations
      at our outpatient seizure unit between the occurrence of epilepsy and
      commencement of the study. The clinical criteria for inclusion in this study were
      brain injury by trauma, stroke or intracerebral hemorrhage, documented by CT
      scan, and the occurrence of this so-called index event in patients with
      established chronic epilepsy. These requirements were met by 63 patients (40
      male, mean age 44.8 years, SD 14.7 a; 23 female, mean age 43.1 years, SD 16.4 a).
      Seizure characteristics, EEG recordings as well as seizure frequencies before and
      after the index event were compared. Patients and controls were observed for a
      mean time of 22.12 years (SD 7.33 a) and 22.01 years (SD 11.31 a), respectively.
      Two patients presenting with generalized seizures prior to brain injury underwent
      a change in seizure characteristics. One control (without intercurrent brain
      lesion; matched for age, sex, age at onset of seizure disorder and classification
      of seizure disorder) primarily presenting with partial seizures evolving to
      generalized seizures showed changed seizure characteristics. These changes are
      statistically insignificant (McNemar test for the significance of changes).
      Seizure frequencies decreased significantly after brain injury. EEG recordings
      mirrored clinical findings with additional focal aspects according to brain
      lesion. These findings are discussed mainly with respect to the cofactorial
      etiology of epilepsies.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7813416
TI  - Opiate receptors in idiopathic generalised epilepsy measured with
      [11C]diprenorphine and positron emission tomography.
AB  - The neurochemical basis of absence seizures is uncertain. A previous PET study
      has provided evidence for release of endogenous opioids from cerebral cortex at
      the time of absence seizures, but it is has not yet been established whether
      there is an abnormality of opiate receptor numbers interictally. In the present
      study, the non-specific opiate receptor ligand, [11C]diprenorphine, was used to
      measure cerebral opiate receptors interictally in patients with childhood and
      juvenile absence epilepsy. Eight patients and eight normal controls had a single
      scan after a high specific activity injection of [11C]diprenorphine. The cerebral
      volume of distribution (Vd) of [11C]diprenorphine relative to plasma was
      calculated on a pixel-by-pixel basis. There were no significant differences in
      [11C]diprenorphine Vd between patients and control subjects in either cortex or
      thalamus, structures thought to be involved in the pathogenesis of absence
      seizures. The results suggest that there is no overall abnormality of opioid
      receptors in patients with childhood and juvenile absence epilepsy. Studies with
      specific ligands may provide information about the different receptor subtypes.

PMID- 7813417
TI  - Survey of 260 epileptic patients treated with oxcarbazepine (Trileptal) on a
      named-patient basis.
AB  - We report the clinical findings on all 260 epileptic in- and out-patients of a
      Dutch epilepsy centre ever treated with oxcarbazepine on a named-patient basis.
      All but three patients had been previously treated, in vain, with carbamazepine.
      Of 260 patients, exposed for 935 patient-years, 161 were still treated on
      reference date, the longest duration of oxcarbazepine treatment being 119 months.
      Fourteen patients were lost to follow up. Four successfully stopped treatment
      after full control of their epilepsy for over three years. Seven stopped because
      they got worse instead of better. Seventy-three did not benefit sufficiently to
      continue on OCBZ in view of alternative treatment possibilities. In one patient
      the final diagnosis was pseudo-seizures. The drug is particular useful in
      patients who require polypharmacy and patients with adverse effects to
      carbamazepine.

PMID- 7813419
TI  - Crystal structure of AmiC: the controller of transcription antitermination in the
      amidase operon of Pseudomonas aeruginosa.
AB  - The crystal structure for the negative regulator (AmiC) of the amidase operon
      from Pseudomonas aeruginosa has been solved at a resolution of 2.1 A. AmiC is the
      amide sensor protein in the amidase operon and regulates the activity of the
      transcription antitermination factor AmiR, which in turn regulates amidase
      expression. The AmiC structure consists of two domains with an alternating beta
      alpha-beta topology. The two domains are separated by a central cleft and the
      amide binding site is positioned in this cleft at the interface of the domains.
      The overall fold for AmiC is extremely similar to that for the leucine-isoleucine
      valine binding protein (LivJ) of Escherichia coli despite only 17% sequence
      identity, however, the two domains of AmiC are substantially closed compared with
      LivJ. The closed structure of AmiC is stabilized significantly by the bound
      acetamide, suggesting a molecular mechanism for the process of amide induction.
      The amide binding site is extremely specific for acetamide and would not allow a
      closed conformation in the presence of the anti-inducer molecule butyramide.

PMID- 7813420
TI  - Tyrosinase related protein 1 (TRP1) functions as a DHICA oxidase in melanin
      biosynthesis.
AB  - Several genes critical to the enzymatic regulation of melanin production in
      mammals have recently been cloned and mapped to the albino, brown and slaty loci
      in mice. All three genes encode proteins with similar structures and features,
      but with distinct catalytic capacities; the functions of two of those gene
      products have previously been identified. The albino locus encodes tyrosinase, an
      enzyme with three distinct melanogenic functions, while the slaty locus encodes
      tyrosinase-related protein 2 (TRP2), an enzyme with a single specific, but
      distinct, function as DOPAchrome tautomerase. Although the brown locus, encoding
      TRP1, was actually the first member of the tyrosinase gene family to be cloned,
      its catalytic function (which results in the production of black rather than
      brown melanin) has been in general dispute. In this study we have used two
      different techniques (expression of TRP1 in transfected fibroblasts and
      immunoaffinity purification of TRP1 from melanocytes) to examine the enzymatic
      function(s) of TRP1. The data demonstrate that the specific melanogenic function
      of TRP1 is the oxidation of 5,6-dihydroxyindole-2-carboxylic acid (DHICA) to a
      carboxylated indole-quinone at a down-stream point in the melanin biosynthetic
      pathway. This enzyme activity appears to be essential to the further metabolism
      of DHICA to a high molecular weight pigmented biopolymer.

PMID- 7813418
TI  - Complete DNA sequence of yeast chromosome II.
AB  - In the framework of the EU genome-sequencing programmes, the complete DNA
      sequence of the yeast Saccharomyces cerevisiae chromosome II (807 188 bp) has
      been determined. At present, this is the largest eukaryotic chromosome entirely
      sequenced. A total of 410 open reading frames (ORFs) were identified, covering
      72% of the sequence. Similarity searches revealed that 124 ORFs (30%) correspond
      to genes of known function, 51 ORFs (12.5%) appear to be homologues of genes
      whose functions are known, 52 others (12.5%) have homologues the functions of
      which are not well defined and another 33 of the novel putative genes (8%)
      exhibit a degree of similarity which is insufficient to confidently assign
      function. Of the genes on chromosome II, 37-45% are thus of unpredicted function.
      Among the novel putative genes, we found several that are related to genes that
      perform differentiated functions in multicellular organisms of are involved in
      malignancy. In addition to a compact arrangement of potential protein coding
      sequences, the analysis of this chromosome confirmed general chromosome patterns
      but also revealed particular novel features of chromosomal organization.
      Alternating regional variations in average base composition correlate with
      variations in local gene density along chromosome II, as observed in chromosomes
      XI and III. We propose that functional ARS elements are preferably located in the
      AT-rich regions that have a spacing of approximately 110 kb. Similarly, the 13
      tRNA genes and the three Ty elements of chromosome II are found in AT-rich
      regions. In chromosome II, the distribution of coding sequences between the two
      strands is biased, with a ratio of 1.3:1. An interesting aspect regarding the
      evolution of the eukaryotic genome is the finding that chromosome II has a high
      degree of internal genetic redundancy, amounting to 16% of the coding capacity.

PMID- 7813422
TI  - Possible pheromone-carrier function of two lipocalin proteins in the vomeronasal
      organ.
AB  - We report the molecular cloning and characterization of two secretory proteins
      specifically expressed in vomeronasal and posterior glands of the nasal septum,
      the ducts of which open into the lumen of the vomeronasal organ. These two
      proteins are members of the lipocalin superfamily, consisting of hydrophobic
      ligand carriers. We immunohistochemically localized one of the proteins in the
      mucus covering the vomeronasal sensory epithelium, where the primary reception of
      pheromone takes place. The immunoreactivity on the vomeronasal sensory epithelium
      was evident in the neonatal and post-pubertal periods, when the close contact
      between animals plays critical roles in suckling and sexual behaviors,
      respectively. These results suggest that small lipophilic molecules stimulate the
      accessory olfactory system to regulate the reproductive behavior of mice.

PMID- 7813423
TI  - Recruitment of plasma membrane voltage-dependent calcium-permeable channels in
      carrot cells.
AB  - Numerous biological assays and pharmacological studies have led to the suggestion
      that depolarization-activated plasma membrane Ca2+ channels play prominent roles
      in signal perception and transduction processes during growth and development of
      higher plants. The recent application of patch-clamp techniques to isolated
      carrot protoplasts has led to direct voltage-clamp evidence for the existence of
      Ca2+ channels activated by physiological depolarizations in the plasma membrane
      of higher plant cells. However, these voltage-dependent Ca2+ channels were not
      stable and their activities decreased following the establishment of whole-cell
      recordings. We show here that large pre-depolarizing pulses positive to 0 mV
      induced not only the recovery of Ca2+ channel activities, but also the activation
      of initially quiescent voltage-dependent Ca2+ channels in the plasma membrane
      (recruitment). This recruitment was dependent on the intensity and duration of
      membrane depolarizations, i.e. the higher and longer the pre-depolarization, the
      greater the recruitment. Pre-depolarizing pulses to +118 mV during 30 s increased
      the initial calcium currents 5- to 10-fold. The recruited channels were permeable
      to Ba2+ and Sr2+ ions. The data suggested that voltage-dependent Ca(2+)-permeable
      channels are regulated by biological mechanisms which might be induced by large
      pre-depolarizations of the plasma membrane. In addition, this study provides
      evidence for the existence in the plasma membrane of higher plant cells of a
      large number of voltage-dependent Ca2+ channels of which a major part are
      inactive and quiescent. It is suggested that quiescent Ca2+ channels can be
      rapidly recruited for Ca(2+)-dependent signal transduction.

PMID- 7813421
TI  - Uncoupling gastrulation and mesoderm differentiation in the Drosophila embryo.
AB  - In Drosophila, ventral furrow formation and mesoderm differentiation are
      initiated by two regulatory genes, twist (twi) and snail (sna). Both genes are
      evolutionarily conserved and have also been implicated in vertebrate
      gastrulation. Evidence is presented that sna is sufficient to initiate the
      invagination of the ventral-most embryonic cells in the absence of twi+ gene
      activity. The invaginated cells fail to express mesoderm regulatory genes,
      suggesting that ventral furrow formation can be uncoupled from mesoderm
      differentiation. Despite the previous demonstration that sna functions as a
      sequence-specific transcriptional repressor, low levels of sna that fail to
      repress neuroectoderm determinants in the presumptive mesoderm are nonetheless
      able to promote invagination. Cells that possess an ambiguous developmental
      identity can initiate the invagination process, providing further evidence that
      ventral furrow formation need not be linked to mesoderm differentiation.

PMID- 7813424
TI  - Interfacial self-assembly of a hydrophobin into an amphipathic protein membrane
      mediates fungal attachment to hydrophobic surfaces.
AB  - The SC3p hydrophobin of Schizophyllum commune is a small hydrophobic protein (100
      101 amino acids with eight cysteine residues) that self-assembles at a water/air
      interface and coats aerial hyphae with an SDS-insoluble protein membrane, at the
      outer side highly hydrophobic and with a typical rodlet pattern. SC3p monomers in
      water also self-assemble at the interfaces between water and oils or hydrophobic
      solids. These materials are then coated with a 10 nm thick SDS-insoluble
      assemblage of SC3p making their surfaces hydrophilic. Hyphae of S. commune
      growing on a Teflon surface became firmly attached and SC3p was shown to be
      present between the fungal cell wall and the Teflon. Decreased attachment of
      hyphae to Teflon was observed in strains not expressing SC3, i.e. a strain
      containing a targeted mutation in this gene and a regulatory mutant thn. These
      findings indicate that hydrophobins, in addition to forming hydrophobic wall
      coatings, play a role in adherence of fungal hyphae to hydrophobic surfaces.

PMID- 7813425
TI  - Soluble receptor-resistant poliovirus mutants identify surface and internal
      capsid residues that control interaction with the cell receptor.
AB  - Poliovirus initiates infection by binding to its cell receptor and undergoing a
      receptor-mediated conformational alteration. To identify capsid residues that
      control these interactions, we have isolated and characterized poliovirus mutants
      that are resistant to neutralization by a soluble form of the poliovirus
      receptor. Twenty one soluble receptor-resistant (srr) mutants were identified
      which still use the poliovirus receptor to infect cells. All but one srr mutant
      contain a single amino acid change at one of 13 different positions, either on
      the surface or in the interior of the virion. The results of binding and
      alteration assays demonstrate that both surface and internal capsid residues
      regulate attachment to the receptor and conformational change of the virus.
      Mutations that reduce alteration also affect receptor binding, suggesting a
      common structural basis for early events in poliovirus infection.

PMID- 7813426
TI  - Rational design of a receptor super-antagonist of human interleukin-6.
AB  - Interleukin-6 (IL-6) is a differentiation and growth factor for a variety of cell
      types and its excessive production plays a major role in the pathogenesis of
      multiple myeloma and post-menopausal osteoporosis. IL-6, a four-helix bundle
      cytokine, is believed to interact sequentially with two transmembrane receptors,
      the low-affinity IL-6 receptor (IL-6R alpha) and the signal transducer gp130, via
      distinct binding sites. In this paper we show that combined mutations in the
      predicted A and C helices, previously suggested to establish contacts with gp130,
      give rise to variants with no bioactivity but unimpaired binding to IL-6R alpha.
      These mutants behave as full and selective IL-6 receptor antagonists on a variety
      of human cell lines. Furthermore, a bifacial mutant was generated (called IL-6
      super-antagonist) in which the antagonist mutations were combined with amino acid
      substitutions in the predicted D helix that increase binding for IL-6R alpha. The
      IL-6 super-antagonist has no bioactivity, but improved first receptor occupancy
      and, therefore, fully inhibits the wild-type cytokine at low dosage. The
      demonstration of functionally independent receptor binding sites on IL-6 suggests
      that it could be possible to design super-antagonists of other helical cytokines
      which drive the assembly of structurally related multisubunit receptor complexes.

PMID- 7813427
TI  - Differential tyrosine phosphorylation of the IFNAR chain of the type I interferon
      receptor and of an associated surface protein in response to IFN-alpha and IFN
      beta.
AB  - The human interferon alpha-receptor (IFNAR gene product) is a transmembranal
      protein of 557 amino acids with an intracytoplasmic domain of 100 amino acids
      containing four tyrosines. Antibodies to a C-terminal peptide (residues 521-536)
      were developed which efficiently immunoprecipitate the 105 kDa IFNAR protein from
      detergent extracts of human cells. We show that the IFNAR protein becomes
      tyrosine phosphorylated within 5 min after treatment of human myeloma U266 cells
      with IFN-alpha 2, IFN-alpha 8 or IFN-beta. The IFNAR chain interacts with both
      IFN-alpha 2 and IFN-beta, as demonstrated by cross-linking. Among elements
      involved in signal transduction by type I IFNs, the tyrosine kinase Tyk2 but not
      Jak1, and the ISGF3 transcription factor subunit Stat2 (p113) but not Stat1
      (p91), are found associated with the IFNAR protein. After IFN-beta treatment for
      5 min, a tyrosine-phosphorylated protein of approximately 95 kDa (beta-PTyr) is
      found bound to IFNAR, but can be dissociated by denaturation. The beta-PTyr
      protein is present on the cell surface, like IFNAR, as shown by extracellular
      biotin tagging. The ratio of beta-PTyr to IFNAR tyrosine phosphorylation is much
      higher with IFN-beta than with IFN-alpha 2 or 8. Both are IFN dependent and
      abrogated by a monoclonal antibody which blocks IFNAR action. The beta-PTyr
      component may represent an important difference in the action of IFN-beta as
      compared with IFN-alpha in their shared receptor system.

PMID- 7813428
TI  - A family of proteins containing a conserved domain that mediates interaction with
      the yeast SNF1 protein kinase complex.
AB  - The SNF1 protein kinase is required for the regulatory response to glucose
      starvation in Saccharomyces cerevisiae. SNF1 is a protein serine/threonine kinase
      that has been widely conserved in both plants and mammals. Previously, we
      identified SIP1 and SIP2 as proteins that interact with SNF1 in vivo by the two
      hybrid system. We have cloned the SIP2 gene and the encoded protein is homologous
      to SIP1 and to GAL83, which affects glucose repression of the GAL genes. We show
      that SIP2 and GAL83, like SIP1, co-immunoprecipitate with SNF1 and are
      phosphorylated in vitro. An 80 amino acid sequence, designated the ASC domain, is
      highly conserved at the C-termini of all three proteins. We show that this small
      domain can mediate protein-protein interaction with the SNF1 kinase complex.
      Thus, SIP1, SIP2 and GAL83 define a family of homologous proteins that are
      tightly associated with the SNF1 kinase, probably in alternative forms of the
      complex. Genetic evidence suggests that the three proteins have distinct, but
      related, functions in the SNF1 pathway, and deletion of GAL83 dramatically
      reduces SNF1 activity in immune complex assays. We propose that SIP1, SIP2 and
      GAL83 act as adaptors that promote the activity of SNF1 towards specific targets.

PMID- 7813429
TI  - A temperature sensitive p210 BCR-ABL mutant defines the primary consequences of
      BCR-ABL tyrosine kinase expression in growth factor dependent cells.
AB  - The Philadelphia translocation commonly observed in chronic myeloid leukaemia
      (CML) and a proportion of cases of acute leukaemia results in the creation of a
      chimeric fusion protein, BCR-ABL. The fusion protein exhibits an elevated
      tyrosine kinase activity as compared to normal ABL. Using a temperature sensitive
      mutant of p210 BCR-ABL (ts-p210) we find that the primary effect of BCR-ABL
      expression in an IL-3 dependent cell line is to prolong survival following growth
      factor withdrawal; only a small proportion of cells remain viable and rapidly
      evolve to complete growth factor independence. During passage in the presence of
      IL-3 at the temperature permissive for kinase activity, ts-p210 expressing
      cultures become dominated by completely growth factor independent cells within 10
      30 days. There is also a significant difference between BCR-ABL and IL-3 mediated
      signalling with respect to the MAP kinase pathway; in contrast to IL-3
      stimulation or v-ABL expression, BCR-ABL does not signal ERK 2 (MAP 2 kinase)
      activation, underlining the apparent inability of BCR-ABL to deliver an immediate
      proliferative signal in Ba/F3 cells. Our data suggest that growth factor
      independence does not simply reflect the convergence of BCR-ABL and IL-3 mediated
      signalling pathways and its development, at least in Ba/F3 cells, requires
      prolonged exposure to BCR-ABL kinase activity. We suggest that the myeloid
      expansion characteristic of CML may result from the prolongation of survival of
      myeloid progenitor cells under conditions of limiting growth factor rather than
      their uncontrolled proliferation.

PMID- 7813431
TI  - Proliferative inhibition by dominant-negative Ras rescues naive and neuronally
      differentiated PC12 cells from apoptotic death.
AB  - We have used the nerve growth factor (NGF)-responsive PC12 cell line as a model
      to examine the role of cell cycle progression in apoptotic neuronal cell death
      triggered by withdrawal of trophic support. Because p21 Ras plays a key role in
      mitogenic signaling, we tested whether interference with the activity of this
      protein would affect cell cycle progression and thereby apoptotic death after
      trophic factor deprivation. For this purpose, we exploited PC12 cells transfected
      with an inducible form of dominant-inhibitory Ras. In contrast to non-transfected
      and uninduced cells, which continue to synthesize DNA when deprived of trophic
      support, PC12 cells induced to express dominant-inhibitory Ras showed little
      thymidine incorporation. When non-transfected and uninduced cells were deprived
      of trophic support, these underwent rapid apoptotic death that could be prevented
      by NGF. However, cells in which dominant-inhibitory Ras was induced and which
      were consequently quiescent did not die upon withdrawal of trophic support and
      showed long-term survival in the absence of NGF or other trophic factors.
      Moreover, induction of dominant-inhibitory Ras also rescued non-dividing,
      neuronally differentiated PC12 cells from death caused by NGF withdrawal. These
      findings suggest a relationship between proliferative capacity and neuronal
      apoptosis and raise the hypothesis that following withdrawal of trophic support,
      neurons undergo an unsuccessful and fatal attempt to re-enter the cell cycle.

PMID- 7813432
TI  - A surrogate 15 kDa JC kappa protein is expressed in combination with mu heavy
      chain by human B cell precursors.
AB  - A novel kappa protein, encoded by a germline JC kappa transcript, is expressed by
      normal and leukemic human B cell precursors. The transcript displays an open
      reading frame initiated by a non-AUG codon, and predicts a 15 kDa molecule which
      could be readily confirmed by in vitro translation. Cellular expression was
      demonstrated by immunofluorescence, precipitation and Western blotting.
      Furthermore, 2-D gel electrophoresis revealed that germline JC kappa can
      covalently associate with mu heavy chain at the surface of pre-B cells. We
      therefore propose that during B cell lymphopoiesis, two alternative pathways
      could be operative in which mu heavy chain can either associate with lambda 5 or
      germ-line JC kappa.

PMID- 7813430
TI  - Isolation and characterization of krp, a dibasic endopeptidase required for cell
      viability in the fission yeast Schizosaccharomyces pombe.
AB  - The activation of pro-hormones and many precursor proteins involves cleavage by
      endopeptidases belonging to the subtilisin-like family of enzymes. Here we
      describe the isolation and characterization of the first member of this family
      from the fission yeast Schizosaccharomyces pombe. The enzyme, which has been
      named krp for KEX2-related protease, is a type I membrane-bound endopeptidase
      that cleaves substrates after pairs of dibasic residues. It appears to be
      synthesized as a pre-pro-protein that is likely to undergo processing following
      translocation into the endoplasmic reticulum. Processing has been characterized
      in a cell-free translation/translocation system prepared from Xenopus eggs. Krp
      is N-glycosylated on all five of its potential sites and both the pre-sequence
      and the pro-sequence are quickly removed following translocation, the latter
      probably by autocatalytic cleavage. The inhibitor profile of krp broadly reflects
      the known properties of the eukaryotic subtilisin proteases, while its pH and
      Ca2+ dependence are consistent with it being active within the secretory pathway.
      One of its physiological substrates is likely to be the pheromone precursor pro-P
      factor, which it is shown to process in an in vitro system, but identification of
      other substrates is complicated because, unlike other members of this family, krp
      is essential for cell viability.

PMID- 7813433
TI  - Insect immunity. A transgenic analysis in Drosophila defines several functional
      domains in the diptericin promoter.
AB  - Diptericins are antibacterial polypeptides which are strongly induced in the fat
      body and blood cells of dipteran insects in response to septic injury. The
      promoter of the single-copy, intronless diptericin gene of Drosophila contains
      several nucleotide sequences homologous to mammalian cis-regulatory motifs
      involved in the control of acute phase response genes. Extending our previous
      studies on the expression of the diptericin gene, we now report a quantitative
      analysis of the contribution of various putative regulatory elements to the
      bacterial inducibility of this gene, based on the generation of 60 transgenic fly
      lines carrying different elements fused to a reporter gene. Our data definitively
      identify two Kappa B-related motifs in the proximal promoter as the sites
      conferring inducibility and tissue-specific expression to the diptericin gene.
      These motifs alone, however, mediate only minimal levels of expression.
      Additional proximal regulatory elements are necessary to attain some 20% of the
      full response and we suspect a role for sequences homologous to mammalian IL6
      response elements and interferon-gamma responsive sites in this up-regulation.
      The transgenic experiments also reveal the existence of a distal regulatory
      element located upstream of -0.6 kb which increases the level of expression by a
      factor of five.

PMID- 7813434
TI  - Transformation by homeobox genes can be mediated by selective transcriptional
      repression.
AB  - Altered transcription is a recurrent theme in the field of cancer biology. But
      despite the central role of transcription in transformation, little is known
      about the mechanism by which dominant nuclear oncogenes induce malignancies.
      Homeobox family proteins are prominent examples of transcriptional regulators
      which control development and can function as oncogenes. Here we explore the
      molecular basis for transformation by this class of regulators using Oct-2 and
      Oct-1. We show that the DNA binding POU domains of these proteins are selective
      and sequence-specific transcriptional repressors that produce malignant lymphomas
      when they are expressed in T cells of transgenic mice. Mutagenesis experiments
      identified a specific set of promoters, those containing octamer regulatory
      elements, as the targets for transformation by selective inhibition of gene
      expression.

PMID- 7813435
TI  - The Drosophila GAGA transcription factor is associated with specific regions of
      heterochromatin throughout the cell cycle.
AB  - In virtually all eukaryotes the centromeric regions of chromosomes are composed
      of heterochromatin, a specialized form of chromatin that is rich in repetitive
      DNA sequences and is transcriptionally relatively silent. The Drosophila GAGA
      transcription factor binds to GA/CT-rich sequences in many Drosophila promoters,
      where it activates transcription, apparently by locally altering chromatin
      structure and allowing other transcription factors access to the DNA. Here we
      report the paradoxical finding that GAGA factor is associated with specific
      regions of heterochromatin at all stages of the cell cycle. A subset of the
      highly repetitive DNA sequences that make up the bulk of heterochromatin in D.
      melanogaster are GA/CT-rich and we find a striking correlation between the
      distribution of GAGA factor and this class of repeat. We propose that GAGA factor
      binds directly to these repeats and may thereby play a role in modifying
      heterochromatin structure in these regions. Our observations demonstrate for the
      first time that a transcriptional regulator can associate with specific DNA
      sequences in a fully condensed mitotic chromosome. This may help explain how the
      distinctive character of a committed or differentiated cell can be maintained
      during cell proliferation.

PMID- 7813436
TI  - Sequences required for enhancer blocking activity of scs are located within two
      nuclease-hypersensitive regions.
AB  - The Drosophila 87A7 heat shock locus is bordered, on the proximal and distal
      sides, by two special chromatin structures, scs and scs'. Each structure is
      characterized by two sets of nuclease-hypersensitive sites, located within
      moderately G/C-rich DNA, flanking an A/T-rich nuclease-resistant region. scs and
      scs' have been shown to insulate a white reporter gene from position effects and
      to prevent enhancer-promoter interactions. These and other properties suggest scs
      and scs' might function as chromatin domain boundaries. To identify the DNA
      sequences which are essential for the insulating activity of scs we used an
      enhancer blocking assay based on the white gene. Sequences capable of suppressing
      activation of white by its upstream enhancer elements reside within a 900 bp DNA
      fragment corresponding to the scs chromatin structure. Within this region, DNA
      fragments associated with the two nuclease-hypersensitive regions are essential
      for full enhancer blocking activity, while the central A/T-rich region is
      dispensable. Deletions which remove part of the hypersensitive regions result in
      intermediate levels of white activity. Insulating activity can, however, be
      reconstituted by multimerizing DNA fragments from either hypersensitive region.
      Our results suggest that the scs boundary is assembled from a discrete number of
      functionally redundant DNA sequences located within both hypersensitive regions
      and that boundaries act by decreasing the frequency of enhancer-promoter
      interactions. We also show that certain types of position effects, like those
      involved in dosage compensation, are not efficiently blocked by scs.

PMID- 7813438
TI  - Altering the specificity of signal transduction cascades: positive regulation of
      c-Jun transcriptional activity by protein kinase A.
AB  - Protein phosphorylation is commonly used to modulate transcription factor
      activity. However, all existing genetic evidence for stimulation of transcription
      factor activity by phosphorylation rests on loss-of-function mutations. To
      demonstrate conclusively that phosphorylation of a transcription factor
      potentiates its transactivation potential in vivo, we constructed a c-Jun mutant
      that is phosphorylated by the cAMP-sensitive protein kinase A (PKA) instead of
      the UV- and Ras-responsive protein kinase JNK. The transcriptional activity of
      this mutant is enhanced by PKA, but not by JNK activation. These results provide
      a positive and conclusive proof that phosphorylation of c-Jun on a critical site
      (Ser73) located in its activation domain is directly responsible for enhancing
      its transactivation function.

PMID- 7813437
TI  - Mouse A-myb encodes a trans-activator and is expressed in mitotically active
      cells of the developing central nervous system, adult testis and B lymphocytes.
AB  - C-myb encodes a transcriptional activator that is essential for the development
      of the hematopoietic system but appears to lack major roles in non-hematopoietic
      cells. The identification of two conserved myb-related genes, designated A-myb
      and B-myb, has raised the possibility that these genes are functional equivalents
      of c-myb in non-hematopoietic cells. Here, we report the isolation and
      preliminary characterization of the mouse A-myb gene. Mouse A-myb maps to the
      proximal region of chromosome 1 and encodes a transcriptional activator with
      properties similar to those of the c-myb and v-myb proteins. During embryo
      genesis A-myb is predominantly expressed in several regions of the developing
      central nervous system (CNS) and the urogenital ridge. Expression in the CNS is
      confined to the neural tube, the hindbrain, the neural retina and the olfactory
      epithelium, and coincides with the presence of proliferating immature neuronal
      precursor cells. In the adult mouse, A-myb is expressed during the early stages
      of sperm cell differentiation and in B lymphocytes located in germinal centers of
      the spleen. Taken together, these results suggest a role for A-myb in the
      proliferation and/or differentiation of neurogenic, spermatogenic and B-lymphoid
      cells.

PMID- 7813439
TI  - p53 oligomerization and DNA looping are linked with transcriptional activation.
AB  - We examined the role of p53 oligomerization in DNA binding and in
      transactivation. By conventional electron microscopy (EM) and scanning
      transmission EM, we find that wild-type tetramers contact 18-20 bp at single or
      tandem 19 bp consensus sequences and also stack in apparent register, tetramer on
      top of tetramer. Stacked tetramers link separated DNA binding sites with DNA
      loops. Interestingly, the p53(1-320) segment, which lacks the C-terminal
      tetramerization domain, binds DNA consensus sites as stacked oligomers. Although
      the truncated protein binds DNA with reduced efficiency, it nevertheless induces
      DNA looping by self-association. p53, therefore, has a C-terminal tetramerization
      domain that enhances DNA binding and a non-tetrameric oligomerization domain that
      stacks p53 at consensus sites and loops separated consensus sites via protein
      protein interactions. Using model promoters, we demonstrate that wild-type and
      tetramerization-deficient p53s activate transcription well when tandem consensus
      sites are proximal to TATA sequences and poorly when tandem sites are distal. In
      the presence of proximal sites, however, stimulation by distal sites increases 25
      fold. Tetramerization and stacking of tetramers, therefore, provide dual
      mechanisms to augment the number of p53 molecules available for activation
      through p53 response elements. DNA looping between separated response elements
      further increases the concentration of local p53 by translocating distally bound
      protein to the promoter.

PMID- 7813440
TI  - Regulated degradation of the transcription factor Gcn4.
AB  - We report that Gcn4, a yeast transcriptional activator of the bZIP family
      involved in the regulation of the biosynthesis of amino acids and purines, is
      rapidly turned over. This degradation is inhibited under conditions of starvation
      for amino acids. Degradation is also inhibited by single amino acid alterations
      in a region adjacent to the Gcn4 activation domain. Furthermore, we show that
      degradation of Gcn4 proceeds through the ubiquitin pathway, a major proteolytic
      system for cytoplasmic proteins, and is dependent on two specific ubiquitin
      conjugating enzymes, Cdc34 (Ubc3) and Rad6 (Ubc2). As a first step towards
      reconstituting the Gcn4 degradation pathway in vitro, we show that purified Cdc34
      and Rad6 proteins are able to direct the specific ubiquitination of Gcn4.

PMID- 7813441
TI  - Differential repression of transcription factor binding by histone H1 is
      regulated by the core histone amino termini.
AB  - In order to investigate the interrelated roles of nucleosome cores and histone H1
      in transcription repression, we have employed a purified system to analyze the
      function of H1 in the repression of transcription factor binding to nucleosomes.
      H1 binding to nucleosome cores resulted in the repression of USF binding to
      nucleosomes. By contrast, H1 only slightly inhibited the binding of GAL4-AH,
      indicating that H1 differentially represses the binding of factors with different
      DNA-binding domains. H1-mediated repression of factor binding was dependent on
      the core histone amino-terminal tails. Removal of these domains alleviated H1
      mediated repression and increased acetylation of these domains partly alleviated
      repression by H1. H1 binding assays suggest a less stable interaction of histone
      H1 with the core particle in the absence of the amino termini.

PMID- 7813443
TI  - Assembly and disassembly of spliceosomes along a specific pre-messenger RNP
      fiber.
AB  - Transcriptionally active Balbiani ring (BR) genes in the salivary glands of the
      dipteran Chironomus tentans were studied by immunoelectron microscopy to
      establish the distribution of spliceosome components along a specific pre
      messenger ribonucleoprotein (pre-mRNP) fiber. The BR genes are 35-40 kb in size
      with three introns close to the 5' end and one close to the 3' end; a very large
      middle portion lacks introns. As a rule the 5' introns are spliced concomitant
      with transcription in the promoter proximal third of the gene, while the 3'
      intron is spliced post-transcriptionally. The BR genes with growing pre-mRNPs
      were visualized in situ, while completed and released pre-mRNPs were isolated
      from the nucleoplasm and studied unfolded on a grid surface. An anti-snRNP
      antibody (Y12) bound mainly to the promoter proximal third of the BR gene (86%)
      and only to a minor extent to the middle and distal thirds (7 and 7%
      respectively). An antibody to an hnRNP protein reacted with the proximal, middle
      and distal regions to an increasing extent (17, 38 and 45% respectively),
      reflecting the increase in size of the growing transcription product. In the
      nucleoplasmic pre-mRNP particle only one end of the RNP fiber was labeled by Y
      12, presumably the 3' end; the anti-hnRNP antibody decorated the entire RNP
      fiber. Thus, the snRNPs do not associate along the whole pre-mRNP fiber but
      rather bind to the 5' and 3' ends, i.e. the regions containing the introns. The
      results also imply that the spliceosomes both assemble and disassemble rapidly on
      the pre-mRNP fiber.

PMID- 7813442
TI  - Response to cAMP levels of the Epstein-Barr virus EBNA2-inducible LMP1 oncogene
      and EBNA2 inhibition of a PP1-like activity.
AB  - The expression of the Epstein-Barr virus LMP1 oncogene is regulated by viral and
      non-viral factors in a tissue dependent fashion. The virus encoded transcription
      factor EBNA2 induces its expression in human B-cells. However, this induction
      also requires the contribution of cellular and/or other viral factors. In
      nasopharyngeal carcinoma cells and in cells from Hodgkin's lymphoma, LMP1 gene
      transcription is independent of viral products. Here we show that the effect of a
      factor binding to a cAMP responsive-like element (CRE) in the LMP1 gene
      transcription regulatory sequence (LRS) is essential for efficient promoter
      activity in the DG75 B-cell line and that elevation of cAMP levels in the cells
      induces LRS-derived CAT activity in a CRE dependent fashion. Incubation of two
      EBV-immortalized B-cell lines expressing endogenous EBNA2A with 8-Br cAMP
      increased the levels of the latency associated 66 kDa LMP1 within 2 h.
      Interestingly, LMP1 expression in DG75 cells conferred resistance to the
      inhibitory effect of 8-Br cAMP on cell proliferation. The protein phosphatase 1
      and 2A (PP1 and PP2A, respectively) inhibitor okadaic acid also stimulated LRS
      CAT activity in DG75 cells. EBNA2A from an EBV-immortalized B-cell line co
      immunopurified with a PP1-like protein. An EBNA2A fragment spanning residues 324
      436 fused to the GST protein specifically rescued a PP1/PP2A-like component from
      DG75 cell extracts. This GST-EBNA2A fusion product inhibited a PP1-like activity
      in nuclear extracts from these cells.

PMID- 7813444
TI  - A novel nuclear pore protein Nup133p with distinct roles in poly(A)+ RNA
      transport and nuclear pore distribution.
AB  - Temperature-sensitive nucleoporin nup49-316 mutant cells accumulate poly(A)+ RNA
      inside the nucleus when shifted to restrictive temperature. We performed a
      synthetic lethal screen with this mutant allele to identify further components of
      the mRNA export machinery. A synthetic lethal mutant slv21 was isolated, which
      exhibited a ts phenotype and showed nuclear accumulation of poly(A)+ RNA at 37
      degrees C. The wild-type gene complementing slv21 was cloned and sequenced. It
      encodes a novel protein Nup133p which is located at the nuclear pore complex.
      NUP133 is not an essential gene, but cells in which NUP133 is disrupted grow
      slowly at permissive temperatures and stop growing at 37 degrees C. Concomitant
      with the growth inhibition, nup133- cells accumulate poly(A)+ RNA inside the
      nucleus whereas nuclear import of a karyophilic reporter protein is not altered.
      Strikingly, nup133- cells display extensive clustering of nuclear pore complexes
      at a few sites on the nuclear envelope. However, the nuclear pore clustering
      phenotype and intranuclear accumulation of poly(A)+ RNA are not obligatorily
      linked, since an amino-terminally truncated Nup133p allows normal poly(A)+ RNA
      export, but does not complement the clustering phenotype of nup133- cells.

PMID- 7813446
TI  - A role for Hsp90 in cell cycle control: Wee1 tyrosine kinase activity requires
      interaction with Hsp90.
AB  - Wee1 protein kinase regulates the length of G2 phase by carrying out the
      inhibitory tyrosyl phosphorylation of Cdc2-cyclin B kinase. Mutations were
      isolated that suppressed the G2 cell cycle arrest caused by overproduction of
      Wee1. One class of swo (suppressor of wee1 overproduction) mutation, exemplified
      by swo1-26, also caused a temperature sensitive lethal phenotype in a wee1+
      background. The swo1+ gene encodes a member of the Hsp90 family of stress
      proteins. Swo1 is essential for viability at all temperatures. Swo1
      coimmunoprecipitates with Wee1, showing that the two proteins interact. The swo1
      26 mutant undergoes premature mitosis when grown at a semi-permissive
      temperature. These data strongly indicate that formation of active Wee1 tyrosine
      kinase requires interaction with Swo1, perhaps in a manner analogous to the
      previously demonstrated interaction between Hsp90 and v-src tyrosine kinase.
      These observations demonstrate a unexpected role for Hsp90 in cell cycle control.

PMID- 7813445
TI  - Human cyclin F.
AB  - Cyclins are important regulators of cell cycle transitions through their ability
      to bind and activate cyclin-dependent protein kinases. In mammals several classes
      of cyclins exist which are thought to co-ordinate the timing of different events
      necessary for cell cycle progression. Here we describe the identification of a
      novel human cyclin, cyclin F, isolated as a suppressor of the G1/S deficiency of
      a Saccharomyces cerevisiae cdc4 mutant. Cyclin F is the largest cyclin, with a
      molecular weight of 87 kDa, and migrates as a 100-110 kDa protein. It contains an
      extensive PEST-rich C-terminus and a cyclin box region that is most closely
      related to cyclins A and B. Cyclin F mRNA is ubiquitiously expressed in human
      tissues. It fluctuates dramatically through the cell cycle, peaking in G2 like
      cyclin A and decreasing prior to decline of cyclin B mRNA. Cyclin F protein
      accumulates in interphase and is destroyed at mitosis at a time distinct from
      cyclin B. Cyclin F shows regulated subcellular localization, being localized in
      the nucleus in most cells, with a significant percentage of cells displaying only
      perinuclear staining. Overexpression of cyclin F, or a mutant lacking the PEST
      region, in human cells resulted in a significant increase in the G2 population,
      implicating cyclin F in the regulation of cell cycle transitions. The ubiquitous
      expression and phylogentic conservation of cyclin F suggests that it is likely to
      coordinate essential cell cycle events distinct from those regulated by other
      cyclins.

PMID- 7813447
TI  - The adenovirus E1A protein overrides the requirement for cellular ras in
      initiating DNA synthesis.
AB  - The adenovirus E1A protein can induce cellular DNA synthesis in growth-arrested
      cells by interacting with the cellular protein p300 or pRb. In addition, serum-
      and growth factor-dependent cells require ras activity to initiate DNA synthesis
      and recently we have shown that Balb/c 3T3 cells can be blocked in either early
      or late G1 following microinjection of an anti-ras antibody. In this study, the
      E1A 243 amino acid protein is shown through microinjection not only to shorten
      the G0 to S phase interval but, what is more important, to override the
      inhibitory effects exerted by the anti-ras antibody in either early or late G1.
      Specifically, whether E1A is co-injected with anti-ras into quiescent cells or
      injected 18 h following a separate injection of anti-ras after serum stimulation,
      it efficiently induces cellular DNA synthesis in cells that would otherwise be
      blocked in G0/G1. Moreover, injection of a mutant form of E1A that can no longer
      associate with p300 is just as efficient as wild-type E1A in stimulating DNA
      synthesis in cells whose ras activity has been neutralized by anti-ras. The
      results presented here show that E1A is capable of overriding the requirement of
      cellular ras activity in promoting the entry of cells into S phase. Moreover, the
      results suggest the possibility that pRb and/or pRb-related proteins may function
      in a ras-dependent pathway that enables E1A to achieve this activity.

PMID- 7813448
TI  - Sex-reversing mutations affect the architecture of SRY-DNA complexes.
AB  - The testis determining factor, SRY, is a DNA binding protein that causes a large
      distortion of its DNA target sites. We have analysed the biochemical properties
      of the DNA binding domains (HMG-boxes) of mutant SRY proteins from five patients
      with complete gonadal dysgenesis. The mutant proteins fall into three categories:
      two bind and bend DNA almost normally, two bind inefficiently but bend DNA
      normally and one binds DNA with almost normal affinity but produces a different
      angle. The mutations with moderate effect on complex formation can be transmitted
      to male progeny, the ones with severe effects on either binding or bending are de
      novo. The angle induced by SRY depends on the exact DNA sequence and thus adds
      another level of discrimination in target site recognition. These data suggest
      that the exact spatial arrangement of the nucleoprotein complex organized by SRY
      is essential for sex determination.

PMID- 7813449
TI  - Tc1 transposase of Caenorhabditis elegans is an endonuclease with a bipartite DNA
      binding domain.
AB  - The Tc1 transposon of Caenorhabditis elegans is a member of the Tc1/mariner
      family of mobile elements. These elements have inverted terminal repeats that
      flank a single transposase gene. Here we show that Tc1 transposase, Tc1A, has a
      bipartite DNA binding domain related to the paired domain of mammalian and
      Drosophila genes. Both the DNA binding domain of Tc1A and the DNA binding site in
      the inverted repeat of Tc1 can be divided into two subdomains. Methylation
      interference studies demonstrate adjacent minor and major groove contacts at the
      inner part of the binding site by the N-terminal 68 amino acids of the DNA
      binding domain. In addition, Tc1A amino acids 69-142 are essential for major
      groove contacts at the outer part of the binding site. Recombinant Tc1A is found
      to be able to introduce a single strand nick at the 5' end of the transposon in
      vitro. Furthermore, Tc1A can mediate a phosphoryl transfer reaction. A mutation
      in a DDE motif abolishes both endonucleolytic and phosphoryl transfer activities,
      suggesting that Tc1A carries a catalytic core common to retroviral integrases and
      IS transposases.

PMID- 7813450
TI  - Processing of intermediates in recombination and DNA repair: identification of a
      new endonuclease that specifically cleaves Holliday junctions.
AB  - The formation and subsequent resolution of Holliday junctions are critical stages
      in recombination. We describe a new Escherichia coli endonuclease that resolves
      Holliday intermediates by junction cleavage. The 14 kDa Rus protein binds DNA
      containing a synthetic four-way junction (X-DNA) and introduces symmetrical cuts
      in two strands to give nicked duplex products. Rus also processes Holliday
      intermediates made by RecA into products that are characteristic of junction
      resolution. The cleavage activity on X-DNA is remarkably similar to that of RuvC.
      Both proteins preferentially cut the same two strands at the same location.
      Increased expression of Rus suppresses the DNA repair and recombination defects
      of ruvA, ruvB and ruvC mutants. We conclude that all ruv strains are defective in
      junction cleavage, and discuss pathways for Holliday junction resolution by
      RuvAB, RuvC, RecG and Rus.

PMID- 7813451
TI  - A new class of DNA photolyases present in various organisms including aplacental
      mammals.
AB  - DNA photolyase specifically repairs UV light-induced cyclobutane-type pyrimidine
      dimers in DNA through a light-dependent reaction mechanism. We have obtained
      photolyase genes from Drosophila melanogaster (fruit fly), Oryzias latipes
      (killifish) and the marsupial Potorous tridactylis (rat kangaroo), the first
      photolyase gene cloned from a mammalian species. The deduced amino acid sequences
      of these higher eukaryote genes show only limited homology with microbial
      photolyase genes. Together with the previously cloned Carassius auratus
      (goldfish) gene they form a separate group of photolyase genes. A new
      classification for photolyases comprising two distantly related groups is
      proposed. For functional analysis P.tridactylis photolyase was expressed and
      purified as glutathione S-transferase fusion protein from Escherichia coli cells.
      The biologically active protein contained FAD as light-absorbing cofactor, a
      property in common with the microbial class photolyases. Furthermore, we found in
      the archaebacterium Methanobacterium thermoautotrophicum a gene similar to the
      higher eukaryote photolyase genes, but we could not obtain evidence for the
      presence of a homologous gene in the human genome. Our results suggest a
      divergence of photolyase genes in early evolution.

PMID- 7813452
TI  - Chromosome end formation in phage lambda, catalyzed by terminase, is controlled
      by two DNA elements of cos, cosN and R3, and by ATP.
AB  - The terminase enzyme of phage lambda is a site-specific endonuclease that nicks
      DNA concatemers to regenerate the 12 nucleotide cohesive ends of the mature
      chromosome. The enzyme's DNA target, cos, consists of a nicking domain, cosN, and
      a binding domain, cosB. cosB, situated to the right of cosN, comprises three 16
      bp repeat sequences, R1, R2 and R3. A similar sequence, R4, is present to the
      left of cosN. It is shown here that terminase has an intrinsic specificity for
      cosN which is independent of the R sites. The interaction with cosN is mediated
      by binding to target sites that include 12 bp on the 5', and 2-7 bp on the 3'
      side of the nick. Of the four R sites, only R3 is required for the proper
      formation of ends. When R3 is present, an ATP-charged terminase system correctly
      catalyzes the production of staggered nicks in cosN, at sites N1 and N2 on the
      bottom and top strands, respectively. When ATP is omitted, the bottom strand is
      nicked incorrectly, at the site Nx, 8 bp to the left of N1. If R3 is removed or
      disabled by a point mutation, nicking in cosN becomes dependent upon ATP but,
      even in the presence of ATP, bottom strand nicking is divided between sites N1,
      the correct site, and Nx, the incorrect one. Thus, R3 is an important regulatory
      element and must reside in cis in respect to cosN. Furthermore, cosN substrates
      bearing point mutations at N1 and N2 are nicked at sites Nx and Ny, 8 bp to the
      left of N1 and N2, respectively. When R3 is present and ATP is added, nicking is
      redirected to the N1 and N2 positions despite the mutations present. Thus,
      terminase binding to R3, on one side of cosN, regulates the rotationally
      symmetric nicking reactions on the bottom and top strands within cosN.

PMID- 7813453
TI  - The lambda terminase enzyme measures the point of its endonucleolytic attack 47
      +/- 2 bp away from its site of specific DNA binding, the R site.
AB  - lambda terminase is an ATP-interactive, site-specific endonuclease comprising the
      products of lambda genes Nu1 and A. Terminase binds to cos, at the junction of
      two chromosomes in a concatemer, catalyzes cos cleavage and initiates the
      packaging of lambda DNA into proheads. cos consists of a nicking domain, cosN,
      where terminase cleaves to regenerate the 12 nucleotide cohesive ends of mature
      lambda chromosomes and a binding domain, cosB, where terminase binds to 16 bp
      repeat sequences called R3, R2 and R1. Evidence is presented that terminase is a
      single-strand endonuclease that can nick DNA by one of two mechanisms, both of
      which require ATP. (i) When bound to any R site, terminase nicks the strand
      which, within that R site, is purine-rich; the position of this nick is 47 +/- 2
      nucleotides away from the mid-point of that R site, measured in the 3' direction;
      (ii) enzymes that are not bound to R sites nick DNA within certain specific
      sequences that resemble cosN half sites. These two modes of action are nicely
      combined for the R3-bound protomer that nicks the bottom strand at position N1 in
      cosN since the interval between N1 and the R3 midpoint is 47 nucleotides. Within
      cosN, the bottom and top strand nicks are generated by a rigid protein couple
      with a 2-fold rotational symmetry. The location of both of these nicks, however,
      is gauged asymmetrically from R3, 47 nucleotides away. Again, R1 and R2 are
      separated by 47 bp and orient bound protomers towards each other but, unless the
      DNA between these R sites is lengthened, the enzymes do not nick, indicating an
      inhibitory gpA-gpNu1 apposition.

PMID- 7813454
TI  - An infectious viroid RNA replicon evolved from an in vitro-generated non
      infectious viroid deletion mutant via a complementary deletion in vivo.
AB  - The 359 nucleotides (nt) long potato spindle tuber prototype viroid (PSTVd) is
      sensitive to experimentally introduced mutations as the substitution or deletion
      of a single nucleotide usually abolishes its infectivity, although certain
      sequence alterations are tolerated. This is illustrated by the fact that viroid
      progeny can evolve in planta upon inoculation with substitution mutants generated
      in vitro, and by the existence of genetically stable 356-360 nt long PSTVd field
      isolates. However, to date, no viable in vitro-generated deletion mutant of PSTVd
      has been reported. We have now found a 341 nt long infectious PSTVd RNA replicon
      that evolved in agrotransformed plants transformed with the dimeric form of an in
      vitro-deleted, non-infectious 350 bp long PSTVd cDNA unit by an additional
      complementary deletion of 9 nt in vivo. This is the first report that the
      deletion-abolished infectivity of a viroid is restored by an additional deletion
      that concurrently restabilized its perturbed secondary structure by abandoning an
      internal segment of the rod-like molecule. The fact that approximately 5% of the
      total PSTVd RNA genome was deleted demonstrates that the maintenance of this
      viroid-specific rod-like structure is not only essential for nuclease protection
      but also for the infectivity, i.e. transmissibility, replicability,
      processibility and pathogenicity of these minimal infectious agents.

PMID- 7813455
TI  - Purification and properties of phosphofructokinase from Dictyostelium discoideum.
AB  - Phosphofructokinase (PFruK) from the slime mold Dictyostelium discoideum has been
      purified to homogeneity over 15,000-fold with a 29% yield. Sodium dodecyl
      sulfate/polyacrylamide gel electrophoresis of the final preparation revealed a
      single band of 95 kDa. The native molecular mass was determined by gel filtration
      to be 382 kDa, indicating that the enzyme is a homotetramer. An antibody raised
      in rabbits against the 95-kDa band immunoprecipitated PFruK activity while it did
      not react with the enzyme from yeast and mammalian cells. The apparent pI was 6.8
      and the pH optimum was 7.6. The enzyme had an activation energy (Ea) of 29.1
      kJ/mol. The amino acid composition was distinctive in having high Ser, Gly and
      Glx and low Ala, Val and Tyr compared with other eukaryotic PFruKs. Enzyme
      activity did not have a sigmoidal saturation curve for fructose 6-phosphate, was
      only mildly inhibited by MgATP at acidic pH values, was not affected by enzyme
      concentration and was insensitive to any of the typical allosteric effectors of
      PFruKs from other sources. However, the enzyme binds fructose 2,6-bisphosphate as
      indicated by protection against thermal denaturation. Treatment with cAMP
      dependent protein kinase led to phosphorylation of the enzyme without change in
      activity. The metabolic significance of these properties and their relationship
      to structure/function are discussed.

PMID- 7813456
TI  - Identification and biosynthesis of N1,N9-bis(glutathionyl)aminopropylcadaverine
      (homotrypanothione) in Trypanosoma cruzi.
AB  - Radiolabelling studies using tritiated ornithine, arginine and lysine, together
      with the relevant amino acid decarboxylase enzyme assays, indicate that the
      epimastigote stage of Trypanosoma cruzi is unable to synthesise significant
      amounts of putrescine and cadaverine de novo, compared to the amounts of these
      diamines scavenged from the growth medium. Radiolabelled putrescine is readily
      incorporated into spermidine, spermine and the trypanosomatid-specific polyamine
      glutathione conjugate trypanothione (N1,N8-bis(glutathionyl)spermidine).
      Likewise, radiolabelled cadaverine is incorporated into the analogous polyamines
      aminopropylcadaverine, bis(aminopropyl)cadaverine and another major unidentified
      component. Subsequent studies showed this major component to be a novel polyamine
      thiol conjugate whose structure was confirmed by chemical synthesis to be N1,N9
      bis(glutathionyl)aminopropylcadaverine (homotrypanothione). Kinetic analyses
      using recombinant T. cruzi trypanothione reductase demonstrated that
      homotrypanothione disulphide is readily reduced by this enzyme with kinetic
      parameters similar to trypanothione disulphide, suggesting that it is a
      physiological substrate in vivo. Thus the epimastigote form of T. cruzi differs
      significantly from the African trypanosomes and Leishmania in (a) being unable to
      synthesise significant amounts of diamines de novo, (b) converting significant
      amounts of putrescine and cadaverine to spermine and bis(aminopropyl)cadaverine,
      respectively and (c) the ability to synthesise homotrypanothione as well as
      trypanothione. The implications of these findings with respect to the prospective
      chemotherapy of Chagas' disease are discussed.

PMID- 7813457
TI  - Structural phase transitions involved in the interaction of phospholipid bilayers
      with octyl glucoside.
AB  - The transitional stages induced by the interaction of the nonionic surfactant
      octyl glucoside (OcOse) on phosphatidylcholine liposomes were studied by means of
      transmission electron microscopy (TEM), light scattering and permeability
      changes. A linear correlation was observed between the effective surfactant/lipid
      molar ratio (Re; three-stage model proposed for liposome solubilization) and the
      OcOse concentration in the initial and final interaction stages, despite showing
      almost a constant value during bilayer saturation. The bilayer/aqueous phase
      partition coefficient (K) decreased in the subsolubilizing interaction steps and
      increased during solubilization. Thus, whereas a preferential distribution of
      surfactant monomers in the aqueous phase with respect to the lipid bilayers took
      place in the initial interaction steps, a larger association of OcOse molecules
      with these lipids in bilayers occurred during solubilization. The initial steps
      of bilayer saturation (50-70% permeability) were attained for a lower free
      surfactant (Sw) than that for its critical micellar concentration (cmc). When Sw
      reached the OcOse cmc, solubilization started to occur (Resat). Large unilamellar
      vesicles began to form as the OcOse exceeded 60 mol/100 mol, exhibiting for 65
      mol/100 mol (50% permeability) vesicles of approximately 400 nm. TEM pictures for
      100% permeability (72 mol/100 mol) and Resat still showed unilamellar vesicles,
      albeit that the Resat TEM picture showing traces of smaller structures. Exceeding
      surfactant amounts led to a decrease in static light scattering; the vesicle-size
      curve began to show a bimodal distribution. The TEM picture showed tubular
      structures together with bilayer fragments. Thereafter, the open structures were
      gradually affected by the surfactant and the scattered intensity gradually
      decreased to a constant low value.

PMID- 7813458
TI  - Influence of the four leader sequences of the human insulin-like-growth-factor-2
      mRNAs on the expression of reporter genes.
AB  - The human insulin-like-growth-factor-2 (IGF-2) gene generates mRNAs with four
      different leader sequences, but with identical coding and trailing regions.
      Previous research has revealed that the leader-2-containing and leader-4
      containing mRNAs are completely polysomal, whereas mRNAs possessing leader-3 are
      predominantly present in the untranslated free messenger ribonucleoprotein
      particle (mRNP), both in cell lines and in foetal liver tissue. To investigate
      the influence of the IGF-2 leader sequences on expression of the gene, IGF-2
      leader-luciferase and leader-chloramphenicol acetyltransferase fusion constructs
      were transfected transiently into different cell lines. In these experiments, the
      levels of expression obtained by constructs with leader-1, leader-2 and leader-4
      were very similar, both at the level of mRNA and protein. Leader-3, however,
      strongly repressed the expression of the fusion mRNA via an unknown mechanism.
      This repression appeared to be confined to nucleotides at positions 328-906 of
      the leader sequence. The remaining 5' part of the leader sequence was efficient
      both in RNA expression and in translation, but the 3' part of the leader
      (nucleotides 906-1180) again moderately repressed luciferase expression, possibly
      due to endonucleolytic cleavage in this region of the RNA. To evaluate the effect
      of the IGF-2 leaders on in vitro translation, leader-chloramphenicol
      acetyltransferase fusion mRNAs were synthesized and translated in reticulocyte
      lysates. Compared to a chloramphenicol acetyltransferase control RNA, leader-1
      chloramphenicol acetyltransferase mRNA translated over 20-fold less efficiently,
      whereas leader-2 repressed translation of its chloramphenicol acetyltransferase
      mRNA moderately (3-5 fold). Despite a general improvement of the translation
      efficiency upon translation in HeLa lysate, these discrepancies with the
      transfection data persisted. Translation of leader-3-containing mRNAs in
      reticulocyte lysates was barely detectable. The whole 5' region of leader-3, up
      to nucleotide 614, could be shown to be repressive. Only leader-4 directed
      translation of the chloramphenicol acetyltransferase open reading frame
      efficiently. As with leader-1 and leader-2, this L4-chloramphenicol
      acetyltransferase mRNA translated in a cap-dependent manner under the conditions
      of our experiments; translation of this mRNA was relatively resistant to addition
      of cap analogue. We conclude that all four IGF-2 leader sequences differ in their
      translational properties. This makes it likely that changes in the translational
      machinery will affect the expression of the various IGF-2 mRNAs differentially.

PMID- 7813459
TI  - Preliminary crystallographic studies of four crystal forms of serum albumin.
AB  - Several crystal forms of serum albumin suitable for three-dimensional structure
      determination have been grown. These forms include crystals of recombinant and
      wild-type human serum albumin, baboon serum albumin, and canine serum albumin.
      The intrinsic limits of X-ray diffraction for these crystals are in the range
      0.28-0.22 nm. Two of the crystal forms produced from human and canine albumin
      include incorporated long-chain fatty acids. Molecular replacement experiments
      have been successfully conducted on each crystal form using the previously
      determined atomic coordinates of human serum albumin illustrating the conserved
      tertiary structure.

PMID- 7813460
TI  - Chlorocatechol 1,2-dioxygenase from Rhodococcus erythropolis 1CP. Kinetic and
      immunochemical comparison with analogous enzymes from gram-negative strains.
AB  - Chlorocatechol 1,2-dioxygenase from Rhodococcus erythropolis 1CP was purified to
      homogeneity. In contrast to chlorocatechol 1,2-dioxygenase from Gram-negative
      strains which have a very broad substrate tolerance, the Rhodococcus enzyme was
      relatively more specific and had a distinct preference for 4-substituted
      catechols. Protein and metal analysis indicate an unusual stoichiometry of one
      atom each of iron and manganese/64-kDa homodimer. The N-terminal amino acid
      sequence (27 residues) of the Rhodococcus chlorocatechol 1,2-dioxygenase was
      determined and exhibited 15-22% identity to the published sequences of catechol
      1,2-dioxygenases and other chlorocatechol 1,2-dioxygenases. Antiserum was raised
      in rabbits and antibodies against Rhodococcus chlorocatechol 1,2-dioxygenase were
      affinity purified. Dot-blot analysis revealed a very weak reaction between the
      antibodies and partially purified chlorocatechol 1,2-dioxygenases from
      Alcaligenes eutrophus JMP134 and Pseudomonas putida 87. No reaction between these
      antibodies and above enzymes was observed using Western blotting. Kinetic and
      immunochemical data as well as comparison of subunit molecular mass and suggest
      that the Rhodococcus enzyme differs significantly from the known highly similar
      chlorocatechol 1,2-dioxygenases of Gram-negative strains and seems to be only
      distantly related to them.

PMID- 7813461
TI  - Higher plant light-harvesting complexes LHCIIa and LHCIIc are bound by
      dicyclohexylcarbodiimide during inhibition of energy dissipation.
AB  - We have investigated the binding to proteins of the photosynthetic apparatus of
      the carboxy-modifying agent dicyclohexylcarbodiimide, (cHxN)2C; this inhibits the
      protective dissipation of excess absorbed light energy (qE) by the light
      harvesting apparatus of photosystem II (LHCII), suggesting that carboxyl amino
      acid side chains within hydrophobic protein domains may be involved in qE.
      (cHxN)2(14)C was used to label thylakoids and photosystem II particles, so as to
      identify proteins which may be involved in the detection of lumen pH during qE
      induction. Of six thylakoid proteins labelled with (cHxN)2C under conditions
      where qE is efficiently induced, three are associated with photosystem I, and
      none with the bulk LHCII. PSII-associated label is bound to three minor
      components of LHCII, identified as LHCIIa (two species) and LHCIIc, as shown by
      protein sequencing of tryptic fragments of purified complexes. pH titration of qE
      formation and protein labelling in coupled thylakoids showed that both qE and
      labelling of LHCIIa increased at pH 7-8.

PMID- 7813462
TI  - The relationship between electron flux and the redox poise of the quinone pool in
      plant mitochondria. Interplay between quinol-oxidizing and quinone-reducing
      pathways.
AB  - The dependence of electron flux through quinone-reducing and quinol-oxidizing
      pathways on the redox state of the ubiquinone (Q) pool was investigated in plant
      mitochondria isolated from potato (Solanum tuberosum cv. Bintje, fresh tissue and
      callus), sweet potato (Ipomoea batatas) and Arum italicum. We have determined the
      redox state of the Q pool with two different methods, the Q-electrode and Q
      extraction techniques. Although results from the two techniques agree well, in
      all tissues tested (with the exception of fresh potato) an inactive pool of QH2
      was detected by the extraction technique that was not observed with the
      electrode. In potato callus mitochondria, an inactive Q pool was also found. An
      advantage of the extraction method is that it permits determination of the Q
      redox state in the presence of substances that interfere with the Q-electrode,
      such as benzohydroxamate and NADH. We have studied the relation between rate and
      Q redox state for both quinol-oxidizing and quinone-reducing pathways under a
      variety of metabolic conditions including state 3, state 4, in the presence of
      myxothiazol, and benzohydroxamate. Under state 4 conditions or in the presence of
      myxothiazol, a non-linear dependence of the rate of respiration on the Q-redox
      state was observed in potato callus mitochondria and in sweet potato
      mitochondria. The addition of benzohydroxamate, under state 4 conditions, removed
      this non-linearity confirming that it is due to activity of the cyanide-resistant
      pathway. The relation between rate and Q redox state for the external NADH
      dehydrogenase in potato callus mitochondria was found to differ from that of
      succinate dehydrogenase. It is suggested that the oxidation of cytoplasmic NADH
      in vivo uses the cyanide-resistant pathway more than the pathway involving the
      oxidation of succinate. A model is used to predict the kinetic behaviour of the
      respiratory network. It is shown that titrations with inhibitors of the
      alternative oxidase cannot be used to demonstrate a pure overflow function of the
      alternative oxidase.

PMID- 7813463
TI  - Purification of ATP synthase from Acetobacterium woodii and identification as a
      Na(+)-translocating F1F0-type enzyme.

PMID- 7813464
TI  - Gene-targeting approaches in the study of cellular processes involved in growth
      or differentiation. Advances in the analysis of oncogenes, tumour-suppressor
      genes, cytokine/receptor systems and developmental control genes.

PMID- 7813467
TI  - Detergent-induced folding of the outer-membrane protein PhoE, a pore protein
      induced by phosphate limitation.
AB  - The folding of the in vitro synthesized outer-membrane protein PhoE, a protein
      induced by phosphate limitation, has previously been studied using
      immunoprecipitation experiments with monoclonal antibodies that recognize
      conformational epitopes [De Cock, H., Hendricks, R., de Vrije, T. & Tommassen, J.
      (1990) J. Biol. Chem. 265, 4646-4651]. A folded monomer of the protein was
      detected in this way, while the addition of outer membranes was required to
      induce trimerization. In this study, we demonstrate that the folding of the in
      vitro synthesized PhoE protein did not occur spontaneously, but was dependent on
      the detergent that was present in the immunoprecipitation buffer. A remarkable
      specificity of phenyl-containing detergents on the efficient in vitro folding of
      PhoE molecules was observed. Furthermore, trimerization was detected in the
      absence of outer membranes when such detergents were present. However, the rate
      of trimerization was increased by the addition of crude cell envelopes containing
      outer membranes. The outer membranes probably enhanced trimerization by
      concentrating the folded PhoE molecules.

PMID- 7813466
TI  - Processing of U14 small nucleolar RNA from three different introns of the mouse
      70-kDa-cognate-heat-shock-protein pre-messenger RNA.
AB  - U14 is a small nucleolar RNA required for the processing of eukaryotic rRNA
      precursors. The U14 genes of mouse as well as rat, hamster, human, Xenopus and
      trout are encoded within introns of the constitutively expressed 70-kDa-cognate
      heat-shock protein gene (hsc70). We demonstrate here that U14.6 and U14.8 snRNAs,
      in addition to the previously characterized U14.5, are processed from their
      respective introns when hsc70 pre-mRNA transcripts containing these intronic
      snRNAs are injected into Xenopus oocyte nuclei. Identical intermediates are
      observed in the processing of all three mouse U14 snRNAs indicating similar
      processing pathways. The production of U14 snRNA processing intermediates
      possessing either mature 5' or 3' termini demonstrated that processing can occur
      at either end independent of maturation at the other terminus. Processing of
      U14.6 from hsc70 intron 6 is not dependent upon the base pairing of intron
      sequences flanking the 5' and 3' termini of the encoded U14 snRNA molecule.
      Therefore, excision of an intronic snRNA does not require extending the 5',3'
      terminal helix of U14 snRNA secondary structure into flanking intron regions as
      originally suggested. Microinjection of the plasmid vector containing the mouse
      hsc70/U14.5 snRNA coding region revealed that undetermined plasmid sequences can
      serve as non-specific promoters to generate spurious RNA transcripts. The
      processing of these transcripts and examination of the plasmid-initiated
      transcriptional-start sites indicated that a U14-specific promoter is not present
      in or around the intron-encoded U14.5 gene. These results strongly suggest that
      biosynthesis of mouse U14 snRNA results from an intron-processing pathway.

PMID- 7813465
TI  - Genomic cloning and sequence analyses of the bovine alpha-, beta A- and beta B
      inhibin/activin genes. Identification of transcription factor AP-2-binding sites
      in the 5'-flanking regions by DNase I footprinting.
AB  - Inhibins and activins are dimeric peptide hormones that regulate the circulating
      levels of follicle-stimulating hormone (FSH). In turn, FSH stimulates inhibin
      gene expression in the ovarian follicle; studies to date suggest that this effect
      is mediated by cAMP and that a cAMP-responsive element, identified in the 5'
      flanking region of the alpha-inhibin gene, at least partially effects this
      response. To explore further the transcriptional regulation of the
      inhibin/activin genes, we have isolated and sequenced the 5'-flanking regions of
      the bovine alpha-, beta A- and beta B-inhibin/activin subunit genes and have
      analysed these regions by primer-extension analysis and DNase I footprinting with
      the transcription factor AP-2. Analyses indicated that all three gene promoter
      regions have a number of AP-2-binding sites that are resistant to competition by
      poly(dI-dC), suggesting that cAMP may control the inhibin/activin ratio by
      operating through alternative signal-transduction pathways or that
      inhibin/activin gene expression may be controlled by signals operating through
      the protein kinase C pathway. A comparison of the DNA sequences protected by AP-2
      against DNase I digestion revealed a consensus AP-2-binding site of 5'-GSCCCDSS
      3', where S represents a base pairing involving three (C or G) hydrogen bonds and
      D represents any base other than C. The nucleotide sequences of the bovine beta
      subunit structural genes also are reported.

PMID- 7813468
TI  - Mo(V) electron paramagnetic resonance signals from the periplasmic nitrate
      reductase of Thiosphaera pantotropha.
AB  - A Mo(V) electron paramagnetic resonance (EPR) study of the periplasmic
      respiratory nitrate reductase of the denitrifying bacterium Thiosphaera
      pantotropha has revealed that the molybdenum centre of this enzyme is very
      similar to that in the assimilatory nitrate reductase of Azotobacter vinelandii
      but is somewhat different from that of the membrane-bound bacterial respiratory
      nitrate reductases such as those of Escherichia coli and Paracoccus
      denitrificans. We have identified the Mo(V) species most likely to be the
      catalytically relevant one and characterised two other sets of Mo(V) EPR signals.
      As well as exhibiting EPR signals with g values typical of bacterial molybdenum
      containing reductases, molybdenum-hydroxylase-like EPR signals can be elicited in
      the nitrate reductase of T. pantotropha upon treatment with excess dithionite.
      The only other enzyme known to display this phenomenon is the periplasmic
      dimethylsulphoxide reductase of Rhodobacter capsulatus. A mechanism for the
      generation of these signals is proposed which invokes reduction of the pterin
      ring of the molybdenum cofactor linked to GMP from the dihydro to the tetrahydro
      state. The possibilities and implications of there being cysteine ligands to the
      molybdenum centres of these two enzymes are discussed.

PMID- 7813469
TI  - The energetics and sodium-ion dependence of N5
      methyltetrahydromethanopterin:coenzyme M methyltransferase studied with
      cob(I)alamin as methyl acceptor and methylcob(III)alamin as methyl donor.
AB  - N5-Methyltetrahydromethanopterin:coenzyme M methyltransferase from methanogenic
      Archaea is a membrane-associated enzyme complex that uses a methyl-transfer
      reaction to drive an energy-conserving sodium-ion pump. Methyl transfer occurs in
      two steps, first from N5-methyltetrahydromethanopterin (CH3-H4MPT) to an enzyme
      bound cob(I)amide prosthetic group, and secondly from the methylated cobamide to
      coenzyme M (H-S-CoM). In this study, we report that methyltransferase can also
      use exogenous cob(I)alamin and methylcob(III)alamin as methyl acceptor and methyl
      donor, respectively. The enzyme catalyzes methylcob(III)alamin formation from CH3
      H4MPT and cob(I)alamin (reaction a), and methyl-coenzyme M formation from
      methylcob(III)alamin and H-S-CoM (reaction b). Both reactions were shown to be
      reversible. Reaction a was catalyzed at approximately the same rate (3 U/mg) and
      reaction b at approximately 10% the rate (0.3 U/mg) of the physiological
      reaction, namely methyl transfer from CH3-H4MPT to H-S-CoM. The free energy
      changes (delta G0') associated with reactions a and b were both between -10
      kJ/mol and -20 kJ/mol, consistent with a free energy change of approximately -30
      kJ/mol determined for the physiological reaction. Reaction b but not reaction a
      was sodium-ion dependent. Assuming that methylation of exogenous cob(I)alamin and
      demethylation of exogenous methylcob(III)alamin mimic methylation and
      demethylation of the enzyme-bound corrinoid prosthetic group, it can be inferred
      that methyl transfer from the methylated cobamide prosthetic group to H-S-CoM is
      a site of coupling with sodium-ion translocation.

PMID- 7813470
TI  - Thermodynamics of the formylmethanofuran dehydrogenase reaction in
      Methanobacterium thermoautotrophicum.
AB  - Purified formylmethanofuran dehydrogenase from Methanobacterium
      thermoautotrophicum, which is a thermophilic methanogenic Archaeon growing on H2
      and CO2, was shown to catalyze the reversible reduction of CO2 to N
      formylmethanofuran with 1,1',2,2'-tetramethylviologen (E'0 = -550 mV) as electron
      donor. The rate of CO2 reduction was approximately 25 times higher than the rate
      of N-formylmethanofuran dehydrogenation. From determinations of equilibrium
      concentrations at 60 degrees C and pH 7.0 a midpoint potential (E'0) for the CO2
      + methanofuran/formylmethanofuran couple of approximately -530 mV was estimated.
      The initial step of methanogenesis from CO2 thus has a midpoint potential
      considerably more negative than that of the H+/H2 couple (E'0 = -460 mV at 60
      degrees C). Evidence is described indicating that the as-yet unidentified
      physiological electron donor of the formylmethanofuran dehydrogenase is present
      in the soluble cell fraction.

PMID- 7813471
TI  - The sum of flux control coefficients in the electron-transport chain of
      mitochondria.
AB  - The sum of the flux control coefficients for group-transfer reactions such as
      electron transport has been proposed to be two when the coefficients are
      calculated from experiments in which the concentrations of the electron carriers
      are changed (CE) but one when they are calculated from changes in the rates of
      the electron-transfer processes (Cv). We tested this proposal using electron
      transport in uncoupled beef heart, potato tuber and rat liver mitochondria.
      First, with ascorbate plus N,N,N',N"-tetramethyl-p-phenylenediamine as substrate,
      the CE flux control coefficients of ascorbate, N,N,N',N"-tetramethyl-p
      phenylenediamine, mitochondria and oxygen over electron-transport rate were
      measured by direct titration of the concentrations of these electron carriers. CE
      values were close to zero, one, one and zero, respectively, giving a sum of CE
      flux control coefficients of approximately two. At higher concentrations of
      N,N,N',N'-tetramethyl-p-phenylenediamine, its CE control decreased and the sum
      decreased towards one as predicted. Secondly, the Cv control coefficients of
      groups of electron-transfer processes with succinate or ascorbate plus N,N,N',N'
      tetramethyl-p-phenylenediamine as substrate were measured. This was achieved by
      measuring the effects of KCN (or malonate or N,N,N',N'-tetramethyl-p
      phenylenediamine) on system flux when intermediates were allowed to relax and on
      local flux when intermediates were held constant. The Cv flux control
      coefficients were calculated as the ratio of the effects on system flux and on
      local flux. The sum of the Cv flux control coefficients was approximately one.
      Whether a sum of one or a sum of two was obtained depended entirely on the
      definition of control coefficients that was used, since either sum was obtained
      from the same set of data depending on the method of calculation. Both
      definitions are valid, but they give different information. It is important to be
      aware of which definition is being used when analysing control coefficients in
      electron-transport chains and other group-transfer systems.

PMID- 7813472
TI  - Inhibition of T7 RNA polymerase transcription by phosphate and phosphorothioate
      triplex-forming oligonucleotides targeted to a R.Y site downstream from the
      promoter.
AB  - The effect of triplex-forming oligonucleotides (TFO) on the transcription
      activity of T7 RNA polymerase has been investigated by an in vitro assay. The
      TFOs, either containing only phosphate (PO2) or phosphate and phosphorothioate
      (POS) internucleotide linkages, were targeted to a 30-bp homopurine.
      homopyrimidine (R.Y) site cloned in plasmid Bluescript KS+ about four helical
      turns downstream from the T7 RNA promoter. Band-shift and ultraviolet absorption
      melting experiments showed that the designed pyrimidine PO2 and POS TFOs form
      stable triple-helical complexes with the R.Y target duplex (the delta GTFO values
      of triplex formation vary from -42 to -63 kJ/mol). The triple-helical complexes
      resulting from POS oligonucleotides were less stable (by 4-12 kJ/mol) than those
      obtained with PO2 analogues, the magnitude of destabilization being dependent on
      the number of POS groups present in the third strand. The designed TFOs were
      shown to efficiently repress bacteriophage T7 RNA polymerase transcription under
      different experimental conditions. The repression depended on pH, TFO
      concentration and temperature. When the TFO/template ratio was fixed to 100, a
      strong repressive effect was observed with normal and phosphorothioate pyrimidine
      TFOs, also under physiological conditions. In contrast, a purine-rich
      oligonucleotide containing 44% of guanine residues promoted only a weak
      transcription inhibition, even at a TFO/template ratio as high as 750. Both PO2-
      and POS-containing pyrimidine TFOs produced their strong repressive effect on T7
      RNA polymerase transcription even when they were added to the reaction mixture
      simultaneously with the polymerase. A mechanism of transcription repression is
      discussed. The data reported in this paper are useful for designing
      oligonucleotides acting as artificial repressors in the antigene strategy and
      indicate that the R.Y target need not to be precisely confined to the promoter.

PMID- 7813473
TI  - Unique primary structure of 2-nitropropane dioxygenase from Hansenula mrakii.
AB  - We have isolated the gene encoding 2-nitropropane dioxygenase from Hansenula
      mrakii, an FAD enzyme that catalyzes the oxygenative denitrification of various
      anionic nitroalkanes. The gene contained an open reading frame consisting of 1122
      nucleotides corresponding to 374 amino acid residues. The protein molecular mass
      was estimated to be 41,466 Da, which was similar to the subunit molecular mass of
      the enzyme determined by SDS/PAGE. Several FAD enzymes such as D-amino acid
      oxidase and glucose oxidase also catalyze the oxidation of nitroalkanes as a side
      reaction, although not so efficiently [Kido, T. & Soda, K. (1984) Arch. Biochem.
      Biophys. 234, 468-475]. However, we found no proteins in the databases (GenBank,
      EMBL, PIR and SWISS-PROT) which are homologous to 2-nitropropane dioxygenase of
      H. mrakii in primary structure. No protein motifs, including a nucleotide-binding
      motif, GXGXXG, were found in PROSITE, a database of biologically significant
      protein sites and patterns. Accordingly, 2-nitropropane dioxygenase is a new type
      of flavoprotein with a unique structure.

PMID- 7813474
TI  - Effects of amino acid insertions on the proteolysis of a staphylococcal protein A
      derivative in Escherichia coli.
AB  - In vivo proteolysis of protein ZZT0, derived from the B domain of staphylococcal
      protein A, was investigated in Escherichia coli before and after insertion of 1-3
      multiples of the tetrapeptide Ala-Trp-Trp-Pro close to the C-terminus of ZZT0.
      Before insertion, ZZT0 was proteolytically stable as judged from the purity of
      IgG binding proteins up to 1 h after inhibition of protein synthesis with
      chloramphenicol. Insertion of 1-3 units of Ala-Trp-Trp-Pro into ZZT0 increased
      progressively the sensitivity to proteolysis and induced DnaK and GroEL binding
      to the protein. The time for 50% in vivo hydrolysis of the full length protein
      derivative that was most susceptible to proteolysis, i.e. with three tetrapeptide
      units, was about 40 min when cultivated in a bioreactor and about 4 min in a
      shaken flask culture. Molecular masses and N-terminal sequences of the main
      degradation products indicated that protein ZZT0 is cleaved at identical sites
      irrespective of the number of inserted tetrapeptide units and that the cleavage
      sites are located far from the insertion point. Insertion of another hydrophobic
      amino acid, isoleucine, as the tetrapeptide Ala-Ile-Ile-Pro, only induced a
      slight proteolysis of the ZZT0 molecule under similar conditions. This indicates
      that the insertion of tryptophan residues, rather than of a general hydrophobic
      segment, plays an essential role in the induced proteolysis of the ZZT0 protein.

PMID- 7813475
TI  - Purification and primary structure of metallothioneins induced by cadmium in the
      protists Tetrahymena pigmentosa and Tetrahymena pyriformis.
AB  - Tetrahymena pyriformis and Tetrahymena pigmentosa grown in the presence of a non
      toxic dose of cadmium, accumulate the metal in the cytosol. Purification by gel
      permeation, ion-exchange and reverse-phase high-performance liquid chromatography
      showed that the metal is bound principally to newly formed proteins with
      ultraviolet spectra and cysteine contents similar to those of Cd(2+)
      metallothioneins from multicellular organisms. The isolated proteins revealed
      that the two species of ciliates each express two Cd(2+)-isothioneins. The
      primary structures determined by both Edman degradation and mass spectrometry
      revealed that the equivalent proteins from T. pyriformis and T. pigmentosa have
      identical sequences and that the two isoforms in each species differ only by the
      presence or absence of a lysine residue at the N-terminus. The development of
      automated mass spectrometric sequence analysis algorithms combined with an
      accurate determination of the molecular mass allowed the rapid confirmation of
      the sequences. The Tetrahymena metallothionein sequences are unusually long (105
      and 104 amino acids) and show a unique internal homology which suggests that the
      proteins arose by gene duplication. The chains contain 31 cysteine residues, 15
      of which are arranged in motifs characteristic of the mammalian metallothioneins;
      the remaining residues show several unique repeating motifs, which could have
      interesting consequences for the tertiary structure of the metal-binding sites.
      Amino acid sequences of Tetrahymena metallothioneins have some similarity with
      other eukaryotic metallothioneins. A comparison on the basis of optimised FASTA
      scores, shows a closer relationship with horse metallothionein-1B.

PMID- 7813476
TI  - 1H-NMR assignments and secondary structure of dendroaspin, an RGD-containing
      glycoprotein IIb-IIIa (alpha IIb-beta 3) antagonist with a neurotoxin fold.
AB  - Dendroaspin, also referred to as mambin, was originally isolated from the venom
      of the Elapidae snake Dendroaspis jamesoni kaimose. It shares a high level of
      sequence similarity with the short-chain neurotoxins found in other Elapidae but
      displays approximately 1000-fold lower neurotoxin activity than the closely
      related protein erabutoxin b. However, unlike neurotoxins, it contains an RGD
      (Arg-Gly-Asp) motif and functions as an antagonist of platelet aggregation and
      cell-cell adhesion of comparable potency to the disintegrins from the venoms of
      Viperidae. We have determined the secondary structure of dendroaspin using 1H-NMR
      spectroscopy. Its structure resembles that of the short-chain neurotoxins, with
      three loops extending from a disulphide-bridged core; however, the strands of the
      triple-stranded beta-sheet are shorter and the loop containing the RGD sequence
      is moved away from this sheet. The structure bears little resemblance to that of
      the disintegrins, except in the RGD-containing loop, suggesting that this loop
      may be of prime importance in its inhibitory function. Comparison of this
      preliminary structure with that of the neurotoxins and disintegrins furthers our
      understanding of the mechanism of integrin antagonists and shows how the
      neurotoxin fold can be manipulated to give a variety of inhibitors.

PMID- 7813477
TI  - Analysis of the thermodynamic linkage of DNA binding and ion binding for dimeric
      and tetrameric forms of the lac repressor.
AB  - The salt concentration dependences of the observed association constants (Kobs)
      for the binding of wild-type lac repressor tetramer and the dimeric lacI-18
      mutant repressor to lactose operator DNA were compared. For both proteins, the
      data are consistent with a class of linkage models in which ion binding by the
      protein is driven by differences in the ionic concentrations in bulk solution and
      in the volume near the DNA surface. The models that best agree with the data are
      those in which ion-binding reactions are cooperative. In spite of close agreement
      between these models and the data, the determination of ion stoichiometries and
      apparent ion-binding affinities requires additional mechanistic or structural
      information. The simplest ion-binding mechanism consistent with the data is
      compatible with a current structural model of the repressor-operator complex. At
      salt concentrations in excess of 50 mM, at which cation displacement from the DNA
      and anion displacement from the protein are expected to dominate, similar ion
      stoichiometries are found for the DNA binding of dimeric and tetrameric
      repressors. This supports the notion that the DNA contacts of these proteins are
      homologous. At lower salt concentrations, in which cation binding by the proteins
      is expected to be significant, the net ion stoichiometry of wild-type repressor
      binding is slightly greater than that of the lacI-18 mutant. This difference may
      reflect the availability of ion-binding sites in the distal subunits of tetramer
      that are not present in the dimer, or may be a consequence of the involvement of
      ion binding in the dimer/monomer equilibrium.

PMID- 7813479
TI  - A model for the denaturation and aggregation of beta-lactoglobulin.
AB  - A quantitatively correct kinetic model for the temperature-induced denaturation
      and aggregation of beta-lactoglobulin is presented. The model recognizes an
      initiation, a propagation and a termination step by analogy with polymer radical
      chemistry. The decrease in native beta-lactoglobulin is predicted to follow order
      3/2, in agreement with experimental results. The size of the protein polymer
      particles is predicted to be proportional to the square root of the initial beta
      lactoglobulin concentration. The scattered light intensity is proportional to the
      product of concentration and size of the protein polymer particles. The initial
      increase in scattering intensity of the particles therefore scales with the
      initial squared beta-lactoglobulin concentration. The influence of other reaction
      conditions, e.g. ionic strength and pH, can be incorporated via the reaction
      constants of the reaction kinetic pathway.

PMID- 7813478
TI  - A novel form of mouse cytochrome P450 3A (Cyp3a-16). Its cDNA cloning and
      expression in fetal liver.
AB  - A complementary DNA clone coding for a novel form of cytochrome P450, Cyp3a-16,
      in mouse fetal livers was isolated and completely sequenced. This clone encoded a
      polypeptide of 504 deduced amino acids and showed 87.3% and 66.6% amino acid
      identities with mouse Cyp3a-11 and Cyp3a-13, respectively. Cyp3a-16 transcript
      was detectable before birth and remarkably diminished five weeks after birth in
      mice. We conclude that Cyp3a-16 is a fetal- and puberty-specific cytochrome P450
      in mice.

PMID- 7813480
TI  - Evidence for a loop-like insertion mechanism of pro-Omp A into the inner membrane
      of Escherichia coli.
AB  - We have studied the insertion of pro-OmpA into the Escherichia coli membrane in
      vivo using various mutants that have either alterations in the amino-terminal
      parts of the signal peptide or in the mature region that flanks the signal
      peptide. A pro-OmpA mutant with an amino terminal extension of 142 residues
      derived from ribulokinase (AraB) was analysed for its membrane insertion. The
      AraB portion, which includes a cluster of seven charged residues close to the
      signal sequence, did not interfere with the Sec components and allowed efficient
      export of OmpA. During translocation the AraB portion remained in the cytoplasm.
      Further mutants of OmpA were constructed in the carboxy-terminal region flanking
      the signal sequence. Pro-OmpA does not translocate across the membrane when a
      charge cluster, comprised of Lys-Arg-Arg-Glu-Arg, is introduced after positions
      5, 11 or 15 of the mature region, but is translocated when the cluster is
      introduced after position 22. This defines a region of about 20 residues in the
      mature part of pro-OmpA that is crucial for membrane insertion. These results
      suggest that in the case of the Sec-dependent pro-OmpA, as with the Sec
      independent M13 procoat, the precursor assumes a loop-like structure involving
      the signal peptide and the early part of the mature region, leaving the amino
      terminus of the signal peptide at the cytoplasmic face.

PMID- 7813481
TI  - The phosphotyrosyl phosphatase activator of protein phosphatase 2A. A novel
      purification method, immunological and enzymic characterization.
AB  - A simple, improved procedure for the isolation of the phosphotyrosyl phosphatase
      activator (PTPA) from rabbit skeletal muscle has been developed. The majority of
      the protein phosphatase 2A (PP2A) was separated from PTPA at an early stage in
      the procedure. The procedure yields approximately 1 mg essentially pure PTPA/kg
      rabbit skeletal muscle; it was also applied to porcine brain and the yeast
      Saccharomyces cerevisiae. The physico-chemical properties of PTPA obtained from
      all sources are very similar. The pure rabbit skeletal muscle protein was used to
      raise polyclonal goat antibodies and to affinity purify these antibodies.
      Immunological studies revealed the presence of PTPA in all mammalian tissues and
      cell lines examined with differences in tissue distribution, brain showing the
      highest concentration. PTPA could only be detected in cytosolic fractions. Using
      a semi-quantitative immunological assay (Western blot), the in vivo concentration
      could be estimated to be micromolar, which is in the same range as the PP2A
      target. The purified Xenopus oocyte PTPA showed only a weak cross reactivity,
      whereas yeast PTPA was not recognised by the antibody indicating some
      evolutionary diversity of the protein. In a PTPA-affinity column chromatography,
      the weak interaction with PP2A was independent of the presence of ATP.Mg, a
      necessary cofactor in the activation process. Interaction of PTPA with PP2A in a
      1:1 ratio induces a low (kcat = 3 min-1) ATPase activity that is inhibited by
      okadaic acid, ADP and non-hydrolysable ATP analogues.

PMID- 7813482
TI  - Evidence for domain structures of the trifunctional protein and the
      tetrafunctional protein acting in glyoxysomal fatty acid beta-oxidation.
AB  - In plant glyoxysomes, an enzyme activity responsible for a particular step in the
      fatty acid beta-oxidation is located on more than one protein species. Various
      monofunctional enzymes and two forms of a multifunctional protein are involved in
      the degradation of cis-unsaturated fatty acids. delta 3, delta 2-Enoyl-CoA
      isomerase activity, previously found to be located on a monofunctional dimeric
      protein, is attributable to one form of the monomeric multifunctional protein
      (MFP). The presence or absence of isomerase activity allows us to differentiate
      between the tetrafunctional 76.5-kDa isoform (MFP II) and the trifunctional 74
      kDa isoform (MFP I) in cucumber (Cucumis sativus) cotyledons. Both MFP I and MFP
      II exhibited blocked N-terminal structures. MFP I and MFP II are distinguishable
      from each other by their susceptibility to limited proteolysis. A series of
      examples is presented describing the preparation of enzymically active
      proteolytic fragments. We demonstrate that both forms of the monomeric MFP are
      composed of domains separable from each other without loss of activity. By
      fragmentation of MFP I and subsequent chromatography, a 60-kDa peptide was
      purified retaining hydratase and epimerase activity but lacking dehydrogenase
      activity. In addition, a highly positively charged fragment was observed carrying
      solely dehydrogenase activity. From MFP II, a 36-kDa fragment with hydratase
      activity was characterized. An enzymically inactive 46-kDa fragment was prepared
      from MFP II and sequenced at its unblocked N-terminus.

PMID- 7813484
TI  - Comparison of plasminogen binding and activation on extracellular matrices
      produced by vascular smooth muscle and endothelial cells.
AB  - Plasminogen is the zymogen form of the serine proteinase plasmin. Although
      plasmin functions primarily as a fibrinolytic enzyme, recent evidence from
      numerous laboratories indicates that plasmin is also active in extracellular
      matrix (ECM) proteolysis. The role of plasmin in ECM degradation suggests that
      activation of plasminogen may be regulated by interaction with components of the
      ECM. In the current study, we have investigated binding and kinetic interactions
      between plasminogen, plasminogen activators and ECM synthesized by either
      vascular smooth muscle cells (SMCECM) or endothelial cells (ECECM). We report
      binding of plasminogen, tissue-type plasminogen activator (t-PA) and urinary-type
      plasminogen activator (u-PA) to intact SMCECM with concentrations of ligand
      yielding half-maximal binding (B50) of 34, 5 and 15 nM, respectively. ECECM bound
      only plasminogen and t-PA, with B50 values of 32 nM and 10 nM, respectively. The
      initial rate of t-PA-catalyzed plasminogen activation was enhanced 41-fold in the
      presence of SMCECM and 27-fold on ECECM. In contrast, u-PA-catalyzed activation
      on SMCECM and ECECM was increased only 1.5-fold or 3-fold, respectively. These
      data suggest that the ECM may provide an alternative surface for assembly and
      regulation of plasminogen activation.

PMID- 7813483
TI  - Aspartate-bond isomerization affects the major conformations of synthetic
      peptides.
AB  - The aspartic acid bond changes to an beta-aspartate bond frequently as a side
      reaction during peptide synthesis and often as a post-translational modification
      of proteins. The formation of beta-asparate bonds is reported to play a major
      role not only in protein metabolism, activation and deactivation, but also in
      pathological processes such as deposition of the neuritic plaques of Alzheimer's
      disease. Recently, we reported how conformational changes following the aspartic
      acid-bond isomerization may help the selective aggregation and retention of the
      amyloid beta peptide in affected brains (Fabian et al., 1994). In the current
      study we used circular dichroism, Fourier-transform infrared spectroscopy, and
      molecular modeling to characterize the general effect of the beta-aspartate-bond
      formation on the conformation of five sets of synthetic model peptides. Each of
      the non-modified, parent peptides has one of the major secondary structures as
      the dominant spectroscopically determined conformation: a type I beta turn, a
      type II beta turn, short segments of alpha or 3(10) helices, or extended beta
      strands. We found that both types of turn structures are stabilized by the
      aspartic acid-bond isomerization. The isomerization at a terminal position did
      not affect the helix propensity, but placing it in mid-chain broke both the helix
      and the beta-pleated sheet with the formation of reverse turns. The alteration of
      the geometry of the lowest energy reverse turn was also supported by molecular
      dynamics calculations. The tendency of the aspartic acid-bond isomerization to
      stabilize turns is very similar to the effect of incorporating sugars into
      synthetic peptides and suggests a common feature of these post-translational
      modifications in defining the secondary structure of protein fragments.

PMID- 7813485
TI  - O-demethylation by the homoacetogenic anaerobe Holophaga foetida studied by a new
      photometric methylation assay using electrochemically produced cob(I)alamin.
AB  - The previously studied complete methyl transfer sequence of tetrahydrofolate
      dependent O-demethylation catalyzed by Holophaga foetida strain TMBS4 extracts
      was separated into two steps using cobalamins as non-physiological substrates:
      electrochemically produced cob(I) alamin served as methyl acceptor for phenyl
      methyl ether demethylation, yielding methylcob(III)alamin (reaction I), and
      methylcob(III)alamin served as donor for tetrahydrofolate methylation, yielding 5
      methyl tetrahydrofolate (reaction II). Both reactions were measured with a new
      and direct photometric assay of cob(I)alamin methylation (or the reverse
      reaction) at 540 nm, the isobestic wavelength of the cob(II)alamin/cob(I)alamin
      redox couple (delta epsilon 540 = 4.40 nM-1.cm-1. The rates of reactions I and II
      were proportional to protein concentration, unlike the complete reaction
      sequence. Small components of cell extract did not affect activity of reactions I
      and II. Isovanillate demethylation by extracts of synringate-grown cells
      (reaction I) required reductive activation by cob(I)alamin and was inhibited and
      inactivated by cob(II)alamin, indicating that the reaction mechanism was a
      nucleophilic attack of an enzyme-bound corrinoid in the reduced Co(I) state on
      the methyl carbon of the ether, rather than a radical attack. Only phenyl methyl
      ethers were demethylated; demethylation rates were enhanced by ortho-hydroxyl or
      para-carboxyl groups, but reduced by additional meta substituents. The rate of
      isovanillate demethylation was 81 nmol.min-1.(mg protein)-1 [0.76 mM
      cob(I)alamin] and apparent kinetic constants for cob(I)alamin were: Km = 1.2 mM,
      Vmax = 220 nmol min-1.(mg protein)-1, and Vmax/Km = 180 nmol.min-1.(mg protein)
      1.mM-1 3,5-Dihydroxyanisole demethylation by extracts of 3,5-dihydroxyanisole
      grown cells (also reaction I) was much slower. Reaction II did not require
      activation; specific activity and the specificity constant for
      methylcob(III)alamin were much lower.

PMID- 7813486
TI  - Crystal structure of gamma-oxapentamidine complexed with d(CGCGAATTCGCG)2. The
      effects of drug structural change on DNA minor-groove recognition.
AB  - The crystal structure of the complex of gamma-oxapentamidine and the DNA
      dodecamer d(CGCGAATTCGCG)2 has been determined to a resolution of 0.22 nm and an
      R factor of 18.9%. The gamma-oxapentamidine ligand interacts with the dodecamer
      by classic minor groove binding via interactions within the A+T-rich region of
      the minor groove. A chain of solvent molecules lies along the mouth of the minor
      groove on the outside of the bound ligand. The structural details of the complex
      are discussed and compared with the closely analogous complex with pentamidine
      bound to the same dodecamer [Edwards, K. J., Jenkins, T. C. & Neidle, S. (1992)
      Biochemistry 31, 7104-7109]. The amidinium groups of the ligand do not hydrogen
      bond to bases, but are in close contact with O4' sugar ring atoms. This in part
      explains the reduced DNA binding affinity of this ligand compared to pentamidine.

PMID- 7813487
TI  - Interaction of tryptophan residues of cytochrome P450scc with a highly specific
      fluorescence quencher, a substrate analogue, compared to acrylamide and iodide.
AB  - The cytochrome P450scc tryptophan fluorescence was studied by the use of the
      three quenchers acrylamide, 25-doxyl-27-nor-cholesterol (CNO) and potassium
      iodide (KI). All the nine tryptophan residues were accessible to acrylamide.
      Whereas a strong interaction (static quenching) between acrylamide and tryptophan
      in the active site had been found previously for cytochrome P450c21 [Narasimhulu,
      S. (1988) Biochemistry 27, 1147-1153], in the case of P450scc the temperature
      dependence of the slope of the linear Stern-Volmer plots indicated a dynamic
      quenching mechanism. This mechanism was confirmed by fluorescence lifetime
      measurements. Of the three observed life-times tau 1 = 3.1 +/- 0.5 ns, tau 2 =
      0.7 +/- 0.25 ns and tau 3 = 20 +/- 10 ps, tau 1 decreased noticeably as a
      function of the acrylamide concentration. CNO, a spin-labeled substrate which is
      known to bind tightly to the substrate-binding site of P450scc, quenched 15.5% of
      the total fluorescence. The Lehrer plot of this compound indicated a static
      quenching process with a reciprocal quenching constant of 1/Ks = 4 microM, a
      value which is in accord with the dissociation constant. Our data indicate that
      CNO quenches selectively one or two tryptophan residue(s) in the active site. The
      fluorescence spectrum of the residue(s) accessible to CNO was characterized by a
      red-shifted emission maximum (from 332 nm to 336 nm). The same residue(s)
      appeared to be quenched by potassium iodide, although much less effectively (1/Ks
      = 0.12 M). The most probable candidate for a complex formation with CNO is
      Trp417, which is rather close to Cys422 (the fifth heme ligand). Four arginine
      residues (Arg411, Arg420, Arg425 and Arg426) in the heme peptide may constitute
      the iodide-binding site.

PMID- 7813488
TI  - A new type of Ca(2+)-dependent, Mg(2+)-stimulated ATPase of rat liver plasma
      membrane.
AB  - Incubation of a glycoprotein fraction obtained from rat liver plasma membrane
      which has been previously well characterized using [gamma-32P]ATP results in the
      phosphorylation of a 230-kDa glycoprotein (pgp230). It is composed of a 120-kDa
      subunit (pgp120) and a 110-kDa subunit (pgp110) linked by interchain disulfide
      bonds. Peptide maps of pgp120 and pgp110 suggest extensive similarity in their
      polypeptide chains. Glycan analysis reveals between four and six hybrid-type
      oligosaccharide chains for both phosphoproteins. Immunoblotting using monoclonal
      antibodies and endoglycosidase digestion exclude an identity of pgp120 or pgp110
      with the hepatocyte plasma membrane glycoproteins dipeptidylpeptidase IV or the
      taurocholate transport protein, which co-purify and co-migrate in SDS/PAGE.
      Protein phosphorylation is Ca(2+)-dependent (K0.5(Ca2+) = 0.35 microM, in the
      absence of Mg2+). In the presence of Mg2+, the glycoprotein undergoes rapid
      cycles of phosphorylation and dephosphorylation, resulting in ATPase activity.
      Analysis of phosphorylated amino acids identifies phosphothreonine as the major
      one. Photoaffinity labeling with 8-azido-[alpha-32P]ATP demonstrates the presence
      of one or more ATP binding site(s). Preincubation of pgp230 with various purine
      or pyrimidine nucleotides (ATP, UTP, TTP, ADP, GDP, AMP, CMP) or known P2
      purinoceptor agonists or antagonists (adenosine 5'-[alpha,beta
      methylene]triphosphate, 2-methyl-thio-adenosine 5'-triphosphate, suramin)
      inhibits its phosphorylation by [gamma-32P]ATP. The biological function of pgp230
      is unknown at present. Several findings of the present study are compatible with
      the idea that pgp230 may be involved in a P2-purinoceptor function of the
      hepatocyte. Following this concept, a mechanism is discussed where a
      cytosolically exposed high-affinity Ca(2+)-binding site of pgp230 would allow for
      receptor feedback control, via phosphorylation and dephosphorylation, by sensing
      changes in cytosolic Ca2+ concentration.

PMID- 7813489
TI  - Purification, properties and structural aspects of a thermoacidophilic alpha
      amylase from Alicyclobacillus acidocaldarius atcc 27009. Insight into
      acidostability of proteins.
AB  - The alpha-amylase from the thermoacidophilic eubacterium Alicyclobacillus
      (Bacillus) acidocaldarius strain ATCC 27009 was studied as an example of an
      acidophilic protein. The enzyme was purified from the culture fluid. On an
      SDS/polyacrylamide gel, the protein an apparent molecular mass of 160 kDa, which
      is approximately 15% higher than that predicted from the nucleotide sequence. The
      difference is due to the enzyme being a glycoprotein. Deglycosylation or
      synthesis of the enzyme in Escherichia coli gave a product with the mass expected
      for the mature protein. The amylase hydrolyzed starch at random and from the
      inside, and its main hydrolysis products were maltotriose and maltose. It also
      formed glucose from starch (by hydrolysing the intermediate product maltotetraose
      to glucose and maltotriose) and exhibited some pullulanase activity. the pH and
      temperature optima were pH3 and 75 degrees C, respectively, characterizing the
      enzyme as being thermoacidophilic. Alignment of the sequence of the enzyme with
      that of its closest neutrophilic relatives and with that of alpha-1,4 or alpha
      1,6 glycosidic-bond hydrolyzing enzymes of known three-dimensional structure
      showed that the acidophilic alpha-amylase contains approximately 30% less charged
      residues than do its closest relatives, that these residues are replaced by
      neutral polar residues, and that hot spots for these exchanges are likely to be
      located at the surface of the protein. Literature data show that similar effects
      are observed in three other acidophilic proteins. It is proposed that these
      proteins have adapted to the acidic environment by reducing the density of both
      positive and negative charges at their surface, that this effect circumvents
      electrostatic repulsion of charged groups at low pH, and thereby contributes to
      the acidostability of these proteins.

PMID- 7813490
TI  - The modulation of enzyme reaction rates within multi-enzyme complexes. 1.
      Statistical thermodynamics of information transfer through multi-enzyme
      complexes.
AB  - There is now experimental evidence that association of different enzymes as a
      multi-enzyme complex may result in an alteration of the catalytic properties of
      the enzymes present in this complex. This effect is not related to the
      channelling of reaction intermediates between different active sites. It appears
      as a consequence of an information transfer that occurs within the multi-enzyme
      complex. A theory, based on statistical thermodynamics, has been developed which
      provides an understanding, on a physical basis, for how isologous as well as
      heterologous interactions between identical, or different, enzymes of the complex
      may modulate the catalytic properties of an oligomeric enzyme of that complex.
      The theory predicts three possible types of effects: an alteration, through
      heterologous interactions, of an already existing co-operativity of the
      oligomeric enzyme within the complex; a co-operativity, generated by heterologous
      interactions in the complex that could not occur if the oligomeric enzyme were
      isolated from the rest of the complex; a Michaelis-Menten character of the
      oligomeric enzyme within the complex, but with altered values of Vm and Km
      relative to what would have been observed with the naked enzyme. All these
      effects appear as a consequence of a transfer of information between different
      enzymes of the same multi-protein complex. The following paper in this journal
      shows how one can demonstrate and characterize experimentally these effects in a
      multi-enzyme complex containing ribulose bisphosphate carboxylase-oxygenase.

PMID- 7813491
TI  - The modulation of enzyme reaction rates within multi-enzyme complexes. 2.
      Information transfer within a chloroplast multi-enzyme complex containing
      ribulose bisphosphate carboxylase-oxygenase.
AB  - Octameric ribulose bisphosphate carboxylase-oxygenase binds in an independent
      manner its substrate (ribulose bisphosphate) and a substrate analog (6
      phosphogluconate). The eight active sites of the free enzyme are thus
      independent. The kinetic behaviour of the active site becomes different if
      ribulose bisphosphate carboxylase-oxygenase is inserted in the five-enzyme
      complex previously isolated from chloroplasts. Ribulose bisphosphate carboxylase
      oxygenase then becomes more active than the corresponding free enzyme form. By
      comparing the behaviour of the same enzyme in the free state and in the
      associated state it then becomes possible to study how the thermodynamics of
      protein-protein interactions alters the kinetic behaviour of ribulose
      bisphosphate carboxylase-oxygenase. This alteration may be expressed in terms of
      stabilization-destabilization energies exerted upon the various intermediate
      states of the enzyme reaction, within the multi-protein complex. Heterologous
      interactions within this complex exert a constant stabilization energy on the
      enzyme ground states along the reaction co-ordinate of -1.68 kJ/mol and a
      constant stabilization energy of -3.79 kJ/mol on the enzyme transition states.
      These stabilization energies express how information propagates within the multi
      enzyme complex as to increase the apparent affinity of the substrate for the
      active sites of ribulose bisphosphate carboxylase-oxygenase, as well as to
      increase the catalytic rate constant. The binding of the substrate analog 6
      phosphogluconate to free ribulose bisphosphate carboxylase-oxygenase is non-co
      operative. It becomes positively co-operative if this enzyme is inserted in the
      multi-protein complex. Under these conditions, only one type of enzyme-inhibitor
      complex is detected experimentally. Here again heterologous interactions
      stabilize this enzyme-inhibitor complex relative to that expected if ribulose
      bisphosphate carboxylase oxygenase is free. The extent of stabilization is -1.03
      kJ/mol. Neither free nor associated ribulose bisphosphate carboxylase-oxygenase
      display any co-operativity relative to substrate binding. However, in the
      presence of the substrate analog 6-phosphogluconate, this enzyme displays
      positive co-operativity relative to substrate, although not if it is naked. These
      results can be explained theoretically and show that the maximum value of the
      Hill coefficient is < or = 2. As 6-phosphogluconate and other substrate analogs
      are present in chloroplasts under normal conditions, this co-operativity might be
      of functional importance in vivo.

PMID- 7813492
TI  - Prospective epidemiological study of invasive Haemophilus influenzae disease in
      adults.
AB  - The incidence and characteristics of invasive Haemophilus influenzae disease were
      studied in 43 adult patients admitted to the acute care hospitals in El Valles
      County (Barcelona, Spain) between January 1987 and June 1992. The annual
      incidence of Haemophilus influenzae disease was 1.2 per 100,000 inhabitants.
      Pneumonia occurred in 24 patients, meningitis in five, intraabdominal infections
      in three, obstetric infections in two, epiglottitis in two and cellulitis in one.
      In six patients the source of infection was unknown. Ten (23%) of the infections
      were hospital acquired. Underlying conditions were diagnosed in 30 (70%)
      patients. Nontypeable Haemophilus influenzae strains predominated in all adult
      age groups. Sixty-one percent of type b and 34% of nontypeable strains were
      ampicillin resistant (p = 0.08). Multiple antibiotic resistance was also high
      among type b (53%) and nontypeable (18%) strains. The mortality rate was
      significantly higher in patients with pneumonia, bacteremia from an unidentified
      focus or shock at presentation.

PMID- 7813495
TI  - Limited value of two widely used enzyme immunoassays for detection of Chlamydia
      trachomatis in women.
AB  - Enzyme immunoassays (EIAs) are widely used to diagnose chlamydial infections in
      patients attending genitourinary medicine clinics. They are relatively easy to
      perform and are suitable for testing large numbers of samples. The objective of
      this study was to determine what proportion of women with chlamydial infection,
      defined as the presence of Chlamydia trachomatis in a cervical smear or deposit
      and/or in the urinary tract, detected by means of a sensitive direct fluorescent
      antibody test could also be identified by using two commercially available EIAs
      to test cervical samples. On hundred fifty-one women attending the genitourinary
      medicine clinic at St. Mary's Hospital, London, were enrolled. The use of the
      Chlamydiazyme (Abbott Diagnostics, UK) and MicroTrak (Syva, UK) EIAs resulted in
      the identification of only 56% and 63%, respectively, of women with chlamydial
      infection detected by direct fluorescent antibody staining. Thus, the EIAs
      available for detection of chlamydiae in cervical samples are inadequate for
      identifying all infected women. Improvement might be achieved by testing multiple
      samples or by resorting to tests of greater sensitivity.

PMID- 7813494
TI  - Prevalence of penicillin-resistant viridans streptococci in healthy children and
      in patients with malignant haematological disorders.
AB  - The prevalence of penicillin-resistant viridans streptococci was studied in
      healthy children and in paediatric and adult patients with leukaemia to determine
      whether the frequent presence of penicillin-resistant streptococci in the oral
      cavity of children with leukaemia is the result of antibiotic therapy. Twenty of
      the oral swabs from 50 healthy children who had not received antibiotics in the
      three months prior to sampling yielded viridans streptococci that could be
      cultured on blood agar containing 2 micrograms/ml benzyl-penicillin. In 11 of the
      20 cases the streptococci were resistant to penicillin (MIC > or = 4
      micrograms/ml). This prevalence is significantly higher than that found in adult
      leukaemia patients (40% vs. < or = 5%) but is about the same as that found in
      paediatric patients with leukaemia. The high prevalence of penicillin-resistant
      streptococci in the paediatric age group should be considered when selecting
      therapy and prophylaxis, especially when the risk of infection with one of these
      cocci is enhanced.

PMID- 7813493
TI  - Penicillin G/ofloxacin versus erythromycin/amoxicillin-clavulanate in the
      treatment of severe community-acquired pneumonia.
AB  - In a prospective, randomized, multicenter trial, the efficacy of penicillin plus
      ofloxacin was compared to that of amoxicillin-clavulanate plus erythromycin in
      the treatment of community-acquired pneumonia. One hundred seventeen hospitalized
      patients presenting with severe community-acquired pneumonia received either
      penicillin 3 x 10(6) U/6 h plus ofloxacin 200 mg twice daily (group A) or
      amoxicillin-clavulanate 1 g/6 h plus erythromycin 1 g/8 h (group B). Initial
      assessment included clinical examination, determination of simplified acute
      physiology score (SAPS), chest X-ray and evaluation of microbiological data
      obtained from blood, sputum and/or bronchoscopy. Follow-up was documented at 72 h
      and at 30 days. Both groups were comparable for age, sex, SAPS, chest X-ray,
      hypoxemia and microbiological data. The causative pathogen was identified in 54
      cases (53%), Streptococcus pneumoniae being most frequent isolate (54.7%). All
      organisms cultured were susceptible to at least one of the antibiotics of each
      combination of the protocol, with the exception of two strains of Pseudomonas
      aeruginosa. A favorable outcome was observed in 76% of the patients, equally
      distributed between the two groups. After completion of therapy there were 12
      clinical failures in each group (20.5%). Six patients in each group (10.3%) died
      of infection. Tolerance was similar for both regimens, apart from an increased
      rate of superficial thrombophlebitis in patients receiving intravenous
      erythromycin. The combination of penicillin with ofloxacin is as effective and as
      safe as a previously recommended regimen combining amoxicillin-clavulanate and
      erythromycin in treating patients with community-acquired pneumonia.

PMID- 7813496
TI  - First trimester listeriosis with normal fetal outcome.
AB  - The case of a pregnant woman who in the 13th week of gestation presented with a
      non-specific influenza-like illness ultimately proven to be symptomatic of
      Listeria monocytogenes septicemia, is described. The patient elected to continue
      the pregnancy and following antibiotic therapy recovered and delivered a normal
      infant. At 18 months of age the child was healthy with normal psychomotor
      development. This case underscores the need to consider the possibility of
      Listeria monocytogenes septicemia at any stage of pregnancy, and suggests that
      early institution of antibiotic treatment may result in complete recovery of both
      mother and fetus.

PMID- 7813498
TI  - Severe diarrhea associated with Arcobacter butzleri.
AB  - Two patients with chronic disease (diabetes mellitus type I, hyperuricemia and
      alcohol abuse, respectively) were hospitalized with persistent diarrhea and
      severe abdominal cramps. Using routine methods, the only pathogen isolated in
      stool specimens was Arcobacter butzleri. In both cases acute symptoms subsided
      quickly after antibiotic therapy. After termination of antibiotic treatment,
      Arcobacter butzleri could no longer be detected in stool specimens. Although very
      little is known about the clinical significance of Arcobacter butzleri infections
      in humans, it is highly likely that in both cases Arcobacter butzleri played a
      major causative role in acute disease.

PMID- 7813497
TI  - Guillain-Barre syndrome associated with acute Q fever.
AB  - Several bacterial and viral agents have been implicated in the pathogenesis of
      the Guillain-Barre syndrome, an acquired immune-mediated disorder. A case of
      Guillain-Barre syndrome associated with acute Q fever is described. Coxiella
      burnetii should therefore be added to the list of microorganisms capable of
      inducing the Guillain-Barre syndrome.

PMID- 7813499
TI  - Successful treatment of recurrent cholangitis with antibiotic maintenance
      therapy.
AB  - The impact of antibiotic maintenance therapy on the incidence of biliary tract
      infection was evaluated in patients with recurrent cholangitis after resection of
      a malignancy at the hepatic confluence. Thirty-eight of 54 patients (70%)
      experienced episodes of cholangitis. In 14 of the 38 patients recurrent episodes
      of cholangitis caused a severe interruption of their daily life. These 14 were
      selected for antibiotic maintenance therapy. During maintenance therapy six
      patients experienced no further episodes of cholangitis and five patients a
      marked decrease in the frequency of episodes, while in three patients no
      improvement was seen. Antibiotic maintenance therapy can be highly successful in
      the treatment of recurrent cholangitis after resection of a malignancy at the
      hepatic hilum.

PMID- 7813500
TI  - Prospective study of the impact of broad-spectrum antibiotics on the yeast flora
      of the human gut.
AB  - The effects of four antibiotics on the yeast flora of the human gut were
      evaluated. Forty adult cancer patients who received therapy with amoxicillin
      clavulanate, ciprofloxacin, sulfamethoxazole-trimethoprim or ampicillin were
      studied prospectively. Quantitative stool cultures for yeasts were performed
      immediately before, at the end of and one week after the end of the antibiotic
      treatment. Amoxicillin-clavulanate caused a higher and more persistent increase
      in gastrointestinal colonization by yeasts compared to ciprofloxacin,
      sulfamethoxazole-trimethoprim or ampicillin. The present results are similar to
      those obtained in a mouse model of gastrointestinal colonization by Candida
      albicans when the same antibiotics were used.

PMID- 7813503
TI  - In vitro antimicrobial activity of cefpirome against ceftazidime-resistant
      isolates from two multicenter studies.
AB  - The in vitro activity of cefpirome against ceftazidime-resistant (MIC > 16 mg/l)
      isolates from two multicenter studies was analyzed. The first investigation
      carried out in the USA, was an in vitro comparison of cefpirome and five third
      generation cephalosporins in which more than 6,000 isolates were evaluated,
      including 97 Enterobacteriaceae and 1,509 staphylococci resistant to ceftazidime.
      The second study was a multicenter international study (> 5,000 strains total) in
      which 160 ceftazidime-resistant gram-negative bacilli and 509 staphylococci from
      five countries (Australia, France, Germany, Italy and UK) were tested against
      cefpirome. The results from the US trial indicated that only 0.8% of enteric
      bacilli were resistant to cefpirome compared to 4.9% and 4.7% resistant to
      ceftazidime and cefoperazone, respectively. In the international trial, cefpirome
      was also active against ceftazidime-resistant, class I beta-lactamase producing
      enteric bacilli (75% susceptibility, MIC50 of 4 mg/l) especially against
      Citrobacter spp., Enterobacter spp. and Morganella morganii. Cefpirome was 8- to
      64-fold more active than ceftazidime against seven different staphylococcal
      species. The antimicrobial activity of cefpirome against routine clinical
      isolates and those organisms resistant to third-generation cephalosporins was
      highly consistent within a nation (USA) and among various developed countries.

PMID- 7813501
TI  - Rapid detection of cytomegalovirus infection in immunocompromised patients.
AB  - Several routinely employed diagnostic methods were analysed for their usefulness
      in aiding an early and rapid diagnosis of human cytomegalo-virus infection in
      immunocompromised patients. Clinical samples obtained during an 18-month period
      were examined by conventional culture, the shell vial method, detection of pp65
      antigen and the polymerase chain reaction. Detection of pp65 antigen in
      peripheral leukocytes was the most useful method for rapid detection of infection
      at an early stage. Results of other rapid detection methods, the shell vial
      method and the polymerase chain reaction, gave useful support, while results
      obtained by conventional culture were not available until after the initiation of
      therapy. Only a small proportion of serological tests provided useful information
      for determining whether to treat the patient.

PMID- 7813502
TI  - Retrospective evaluation of a latex agglutination test for diagnosis of invasive
      aspergillosis in immunocompromised patients.
AB  - A commercial latex agglutination (LA) test for the detection of circulating
      Aspergillus galactomannan was evaluated in sera obtained from 121
      immunocompromised patients, including 19 with proven invasive pulmonary
      aspergillosis. Patient urine (the specimen of choice for detection of
      galactomannan) was not tested with the LA test as 34 of 81 specimens from
      controls gave false-positive results. The sensitivity (95%), specificity (90%)
      and negative predictive value (99%) of the LA test were similar to previously
      published results obtained with two EIAs. However, the positive predictive value
      was only 67% compared to > or = 95% obtained with the EIAs. In addition, the LA
      test was also of less value than the EIAs in predicting the onset of invasive
      pulmonary aspergillosis. It was the earliest indicator of infection in only 1 of
      19 proven cases.

PMID- 7813504
TI  - In vitro activity of FK-037, a novel parenteral cephalosporin, against bacterial
      isolates from neutropenic cancer patients.
AB  - The in vitro activity of FK-037, a novel parenteral cephalosporin, was compared
      to that of ceftazidime, aztreonam and piperacillin (agents often used in empiric
      regimens in cancer patients) against recent bacterial isolates from patients with
      cancer. FK-037 was either equal to or 2 to 16-fold more active than the
      comparative agents against members of the Enterobacteriaceae. It was also active
      against Acinetobacter spp., Aeromonas spp., Pseudomonas aeruginosa, and other
      Pseudomonas spp. Xanthomonas maltophilia and Alcaligenes denitrificans were
      relatively resistant to all four agents. FK-037 was also 4 to 16-fold more active
      against most gram-positive organisms (including some methicillin-resistant
      staphylococci) than was ceftazidime. Enterococcus spp., Listeria monocytogenes
      and Staphylococcus haemolyticus were relatively resistant to FK-037 and
      ceftazidime. Overall, FK-037 has a broad antimicrobial spectrum that includes the
      majority of gram-positive and gram-negative isolates.

PMID- 7813505
TI  - Non-puerperal breast infections due to Staphylococcus lugdunensis.

PMID- 7813506
TI  - Infectious arthritis of the knee due to Actinobacillus actinomycetemcomitans.

PMID- 7813507
TI  - Infection by Mycobacterium szulgai in a patient with pulmonary tuberculosis.

PMID- 7813508
TI  - Urinary tract infection caused by quinolone-resistant Campylobacter coli.

PMID- 7813509
TI  - Effect of clavulanic acid on the anti-pseudomonal activity of ticarcillin.

PMID- 7813510
TI  - Murine erythroleukemia (MEL) cells bear ligands for the sialoadhesin and
      erythroblast receptor macrophage hemagglutinins.
AB  - While many studies of erythropoiesis have focused on interactions between
      developing cells and the extracellular matrix, scant attention has been paid to
      the role of erythroid-macrophage interactions in this process. Murine
      erythroleukemia (MEL) cell lines have been used extensively in these studies to
      define erythroid adhesion events. In this study, we compared the adhesion to both
      fibronectin and macrophages of MEL cells and primary fetal liver erythroblasts.
      The avidity of MEL cells for purified mouse fibronectin was greater than that of
      the primary cells. In addition, we have shown that MEL cells carry
      ligands/counter-receptors for sialoadhesin (Sn) and the erythroblast receptor
      (EbR), two hemagglutinins expressed by hematopoietic stromal macrophages. These
      two macrophage-binding activities were independent of erythroid fibronectin
      binding activity. Proteolysis of MEL cell surface receptors was necessary to
      reveal these activities, with this process providing a means for using MEL cells
      as ligand cells in studies of macrophage hemagglutinins. While erythroid adhesion
      to fibronectin and components of the extracellular matrix may be of importance in
      early erythropoiesis, hemagglutinin-expressing stromal macrophages provide the
      appropriate microenvironmental niche for the terminal stages of erythropoiesis
      preceding the release of enucleated cells into the circulation.

PMID- 7813511
TI  - Effects of ouabain and chloride-free medium on isoosmotic volume control and
      ultrastructure of hepatocytes in primary culture.
AB  - Rat hepatocytes in primary monolayer culture have been studied by a combination
      of physiological and morphological approaches under conditions affecting ion
      transport and cell volume. A concentration of ouabain completely inhibiting the
      coupled transport of Na+ and K+ had little effect on cell volume, as indicated by
      cell water content, but induced the formation of many vesicles in the cytoplasm.
      Apparent fusion of vesicles was often observed. By itself, replacement of medium
      Cl by NO3- had little effect on cell volume or morphology. However, when NO3-
      replaced Cl- in the presence of ouabain the cells swelled and the numbers and
      size of vesicles were much reduced. The vesicles accumulating in the presence of
      ouabain showed a yellow fluorescence after the cells were loaded with acridine
      orange, implying that the vesicular contents were acidic. Total fluid-phase
      endocytosis, determined by uptake of Lucifer yellow, was not affected by ouabain
      or the absence of Cl-. However, ouabain considerably retarded the subsequent
      release of Lucifer yellow; this suggests that the dye originally taken into
      endocytotic vesicles became diluted by mixing with contents of ouabain-induced
      vesicles, an explanation consistent with the vesicle fusion seen by electron
      microscopy. The Cl-free medium also retarded Lucifer yellow efflux, to the same
      extent as ouabain, and the effects of the two treatments were not additive. These
      observations are consistent with the activity in hepatocytes of an ouabain
      resistant, Cl(-)-dependent mechanism for cell volume control. It is suggested
      that this depends on the accumulation of water into acidic vesicles, which is
      driven by the Cl(-)-coupled activity of the vacuolar ATPases of the organelles,
      followed by exocytotic expulsion of their contents.

PMID- 7813512
TI  - Identification of R-GRAMP, a membrane glycoprotein of regulated secretory
      granules in primate cells.
AB  - Investigation of membrane assembly and traffic in the regulated secretory pathway
      may be facilitated by identification of membrane components that are unique to
      regulated secretory granules. To identify such markers, we isolated integral
      membrane proteins by Triton X-114 extraction from well-differentiated monolayers
      of an exocrine cell line, the goblet cell subclone (18N2) of the human colon
      carcinoma cell line HT29, and used the extracts as immunogens to produce
      monoclonal antibodies (mAbs). Immunofluorescence microscopy of HT29 goblet cell
      monolayers identified one mAb (MG-1) that labeled a component of mucin granule
      membranes. Immunofluorescence of frozen semithin sections of normal intestine,
      and various other human and monkey tissues, showed that this antigen is present
      in regulated secretory granule membranes of primate exocrine cells, endocrine
      cells, and tissue granulocytes. EM immunogold labeling of goblet cells,
      enteroendocrine cells and eosinophils confirmed that the antigen is associated
      with secretory granule membranes and not with plasma membranes. The antigen was
      identified by SDS-PAGE autoradiography of immunoprecipitates from HT29 goblet
      cells metabolically labeled with [35S]methionine and [35S]cysteine or
      [3H]glucosamine, as a glycoprotein with an apparent molecular mass ranging from
      23 to 37 kDa. Digestion of immunoprecipitates with N-glycosidase F reduced the
      apparent mass to 16 to 19 kDa. This small, highly-glycosylated protein was named
      "R-GRAMP" (for regulated granule-associated membrane protein) to reflect its wide
      distribution in secretory granule membranes of regulated exocrine, endocrine and
      granulocytic cell types. This distribution suggests that it may play a common
      functional role in regulated secretion.

PMID- 7813513
TI  - Surface-associated plasminogen activation in leukemic cells: interaction with
      extracellular matrix.
AB  - In WEHI-3B murine leukemic cells, plasminogen activator and plasminogen binding
      sites are associated with the cell membrane. The putative receptor for the
      zymogen exhibits low affinity for the ligand (dissociation constant of 0.38
      microM and a high binding capacity (40,000 sites per cell). Plasminogen also
      binds in a cooperative fashion to type I collagen with an affinity which is
      higher than that displayed by cells. Collagen-bound plasminogen can be activated
      by cells preincubated with plasminogen in a manner that cells develop the
      capacity to adhere to type I collagen. The activation of collagen-bound
      plasminogen by cellular urokinase-like plasminogen activator (u-PA) was 60% more
      efficient than the activation of the soluble (not bound) form of plasminogen.
      These results suggest that in the invasive phenomena, WEHI cells operate as
      carriers of plasminogen from plasma to tissue. In addition, collagen can serve as
      a reservoir of zymogen in the extracellular matrix milieu through direct binding
      to plasminogen and at the same time allow more efficient plasminogen activation.

PMID- 7813514
TI  - Regional expression of mRNA for proteoglycans and collagen in tendon.
AB  - Regions of tissue that ressemble cartilage develop at the point where tendon
      wraps under a bone and receives compressive forces in addition to tension.
      Northern blot analysis was used to assess expression of mRNA for several
      extracellular matrix constituents in cells immediately after their isolation from
      tensional and compressive regions of fetal, adult and old adult bovine deep
      flexor tendon. Messenger RNA for aggrecan and type II collagen, as well as for
      biglycan and decorin, was highly expressed in cells from the compressed region of
      adult tendon, indicating that this tissue contains cells with a chondrocytic
      phenotype. In contrast, only mRNA for decorin was highly expressed in cells from
      the tensional region of adult tendon. The major developmental changes in mRNA
      expression in the compressed region of tendon included a approximately 25-fold
      increase in aggrecan expression between fetal and adult tissue and an increase in
      type II collagen mRNA from undetectable in fetal tendon to expression in adult
      tendon that was nearly as high as the level expressed in cells from adult
      articular cartilage. Developmental changes in the tensional region consisted of a
      approximately 10-fold decrease in type I collagen expression and a 4-fold
      increase in decorin expression in cells from adult tissue, as compared to fetal
      tissue. These observations indicate that levels of gene expression for
      proteoglycans and collagen in tendon correlate with the mechanical environment in
      the tissue. The regional distinctions in mRNA expression were lost when cells
      were grown in monolayer culture for one week.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7813515
TI  - Identification of decorin proteoglycan in bovine tracheal serous cells in culture
      and localization of decorin mRNA in situ.
AB  - Bovine tracheal submucosal gland serous cells in culture synthesize and secrete
      proteoglycans and not mucin glycoconjugates. We are interested in the
      characterization and role of these proteoglycans in airway secretions. The major
      [35S]methionine-labeled proteoglycan present is identified as the small
      chondroitin/dermatan sulfate proteoglycan decorin (PG II. PG40). Consistent with
      its identity as decorin this proteoglycan showed average apparent molecular
      weights of 75,000 to 130,000 with a core protein of an average, M(r) of about
      40,000 and with glycosaminoglycan chains sensitive to chondroitinase ABC lyase of
      an average M(r) of about 25,000. These data were obtained from gel
      chromatographic and SDS-PAGE analyses. Northern blot analysis and partial amino
      acid sequencing of the purified protein further confirmed its identity as
      decorin. In situ hybridization studies using a decorin riboprobe revealed no
      expression of decorin in the surface epithelium and only low levels of expression
      in submucosal gland epithelial cells of bovine tracheal tissue. However, high
      levels of expression were localized to cells which are peripheral to tracheal
      submucosal gland epithelial cells and which contact with the extracellular
      matrix.

PMID- 7813516
TI  - Heterogeneity of peroxisomes in human hepatoblastoma cell line HepG2. Evidence of
      distinct subpopulations.
AB  - Peroxisomes in human hepatoblastoma cell line HepG2 have been studied using
      immunocytochemical, ultrastructural and biochemical techniques. By
      immunofluorescence, small spherical peroxisomes were seen next to rod-shaped and
      elongated forms. By electron microscopy and catalase cytochemistry, small
      particles with a diameter of 90 to 100 nm were found next to larger ones
      measuring up to 300 nm and some exhibiting tail-like extensions. Both the
      intensity of DAB-staining and the immunolabeling density for catalase were
      heterogenous in different peroxisomes. Contrary to a recent biochemical study,
      the enzyme alanine-glyoxylate-aminotransferase was found by double
      immunofluorescence and immunoelectron microscopy to be localized exclusively in
      peroxisomes of HepG2 cells. By Metrizamide density gradient centrifugation two
      populations of peroxisomes were isolated: a regular fraction banding at 1.20
      g/cm3 with a mean diameter of 222 nm and a lighter peroxisome fraction banding at
      1.14 g/cm3. The ratio of lipid beta-oxidation enzymes to catalase was
      significantly higher in peroxisomes with lower density than in the regular ones.
      These observations show clearly the existence of heterogenous populations of
      peroxisomes in HepG2 cells which may provide a useful model system for the
      investigation of biogenesis and metabolism of peroxisomes of human origin.

PMID- 7813518
TI  - Detection of vitellogenin in a subpopulation of sea urchin coelomocytes.
AB  - Sea urchin vitellogenin is a high molecular weight glycoprotein, which is the
      precursor of the major yolk protein present in the unfertilized egg. Vitellogenin
      processing into the major yolk protein and its further enzymatic cleavage during
      sea urchin embryonic development, has been extensively described, and the
      adhesive properties of the processed molecule have been studied. The function of
      vitellogenin in the adult, where it has been found in the coelomic fluid of both
      male and female individuals, is still unknown, although its role on promoting the
      adhesion of embryonic cells has been shown. In this report we describe the
      detection of vitellogenin in lysates of whole circulating coelomocytes of both
      male and female sea urchins of the species Paracentrotus lividus. By metrizoic
      acid gradients we purified total coelomocytes into six subpopulations that were
      tested for the occurrence of the molecule using vitellogenin-specific polyclonal
      antibodies. We detected vitellogenin only in the coelomocyte subpopulation called
      colorless spherule cells, packed in kidney-shaped granules located around the
      nucleus. We also showed that coelomocytes respond to stress conditions by
      discharging vitellogenin into the medium. This result together with previous
      observations on the adhesive properties of the molecule suggest a role for
      vitellogenin in the clotting phenomenon occurring after host invasion.

PMID- 7813517
TI  - Evolution of alanine:glyoxylate aminotransferase 1 peroxisomal and mitochondrial
      targeting. A survey of its subcellular distribution in the livers of various
      representatives of the classes Mammalia, Aves and Amphibia.
AB  - As part of a wider study on the molecular evolution of alanine:glyoxylate
      aminotransferase 1 (AGT1) intracellular compartmentalization, we have determined
      the subcellular distribution of immunoreactive AGT1, using postembedding protein
      A-gold immunoelectron microscopy, in the livers of various members of the classes
      Mammalia, Aves, and Amphibia. As far as organellar distribution is concerned,
      three categories could be distinguished. In members of the first category (type
      I), all, or nearly all, of the immunoreactive AGT1 was concentrated within the
      peroxisomes. In the second category (type II), AGT1 was found more evenly
      distributed in both peroxisomes and mitochondria. In the third category (type
      III), AGT1 was localized mainly within the mitochondria with much lower, but
      widely variable, amounts in the peroxisomes. Type I animals include the human,
      two great apes (gorilla, orangutan), two Old World monkeys (anubis baboon,
      Japanese macaque), a New World monkey (white-faced Saki monkey), a lago, morph
      (European rabbit), a bat (Seba's short-tailed fruit bat), two caviomorph rodents
      (guinea pig, orange-rumped agouti), and two Australian marsupials (koala,
      Bennett's wallaby). Type II animals include two New World monkeys (common
      marmoset, cotton-top tamarin), three prosimians (brown lemur, fat-tailed dwarf
      lemur, pygmy slow loris), five rodents (a hybrid crested porcupine, Colombian
      ground squirrel, laboratory rat, laboratory mouse, golden hamster), an American
      marsupial (grey short-tailed opossum), and a bird (raven). Type III animals
      include the large tree shrew, three insectivores (common Eurasian mole, European
      hedgehog, house shrew), four carnivores (domestic cat, ocelot, domestic dog,
      polecat ferret), and an amphibian (common frog). In addition to these categories,
      some animals (e.g. guinea pig, common frog) possessed significant amounts of
      cytosolic AGT1. Whereas the subcellular distribution of AGT1 in some orders (e.g.
      Insectivora and Carnivora) did not appear to vary markedly between the different
      members, in other orders (e.g. Primates, Rodentia and Marsupialia) it fluctuated
      widely between the different species. Phylogenetic analysis indicates that the
      subcellular distribution of AGT1 has changed radically on numerous occasions
      during the evolution of mammals. The new observations presented in this paper are
      compatible with our previous demonstration of a relationship between AGT1
      subcellular distribution and either present or putative ancestral dietary habit,
      and our previous suggestion that the molecular evolution of the AGT gene has been
      markedly influenced by dietary selection pressure.

PMID- 7813519
TI  - Rat myoblast fusion requires exteriorized m-calpain activity.
AB  - Our previous studies demonstrated that fibronectin could be proteolyzed by m
      calpain during muscle cell differentiation. Recent results indicated also that m
      calpain could be exteriorized and more particularly associated to extracellular
      matrix components. To clarify one of the possible physiological functions of this
      proteinase during myogenesis, we have analyzed the incidence of added purified m
      calpain and calpain inhibitors on the fusion kinetics of cultured myoblasts. Our
      results provided evidence that at low concentration (0.01 microgram/ml), added m
      calpain induces precocious fusion and increases myoblast fusion by 78%. At high
      concentrations (10 micrograms/ml), the viability of the cells was not affected
      but the myoblasts were unable to fuse. Leupeptin and calpastatin--potent m
      calpain inhibitors--added to the culture medium reduced myoblast fusion by 70%.
      On the other hand, the addition of monospecific m-calpain polyclonal antibodies
      to the culture medium induced a 76% decrease of myoblast fusion. In order to trap
      exteriorized m-calpain, myoblasts were incubated for 24 h with m-calpain
      antibodies. Following this treatment, nonpermeabilized myoblasts exposed to
      labeled secondary antibodies showed fluorescent spots scattered at the cell
      surface. These results strongly support that m-calpain which was involved in
      myoblast fusion was exteriorized and suggest therefore that this enzyme may play
      an important role extracellularly.

PMID- 7813520
TI  - Immortalization of rat hepatocytes by fusion with hepatoma cells. I. Cloning of a
      hepatocytoma cell line with bile canaliculi.
AB  - Hepatocytoma (HPCT) hybrid cells were obtained by fusion of cultured rat
      hepatocytes with Fao Reuber hepatoma cells H35 by polyethylene glycol treatment.
      Surviving cells were cloned in HAT (hypoxanthine-aminopterine-thymidine)/ouabain
      medium and propagated in cell lines over 80 passages. Morphological criteria were
      chosen to allow differentiation of the clones into two types of cells: 1) Type I
      cells which formed irregular cell layers, lacked contact inhibition and resembled
      the parental Fao hepatoma cells and 2) type II cells, which proliferated in
      monolayer cultures, exhibited contact inhibition during growth in culture plates
      and formed bile canaliculi thereby resembling cultured hepatocytes by phenotype.
      Bile canaliculi were absent in type I clones and Fao cells. One particular type
      II clone 1E3 was studied in detail. These cells formed bile canaliculi sealed by
      tight junctions and were comparably polarized as cultured hepatocytes. They
      expressed canalicular antigen B10, canalicular aminopeptidase N, and even
      secreted the fluorescent bile acid derivative NBD-cholate into the canalicular
      lumen. This type of HPCT cells lacked malignancy by tests in vivo and in vitro,
      and contained 110 +/- 5 chromosomes. The cells were considered to represent an
      immortalized hepatocyte-like cell line.

PMID- 7813521
TI  - Immortalization of rat hepatocytes by fusion with hepatoma cells. II. Studies on
      the transport and synthesis of bile acids in hepatocytoma (HPCT) cells.
AB  - Hepatocytoma (HPCT) cells were screened for the uptake of bile acids, the organic
      anion bumetanide and phalloidin. In addition, the rate of bile acid synthesis and
      the ability to conjugate exogenously added free bile acids was investigated. The
      unconjugated bile acid cholate is transported via carrier-mediated uptake into
      HPCT cells of the clone 1E3. This transport is expressed less by HPCT clones 1F9
      and 2E9. Cholate uptake is 40% sodium-dependent, temperature-sensitive, and
      reveals a km-value of 47 +/- 9 pmol/l and a Vmax-value of 94 +/- 29 pmol x min-1
      x mg-1. However, all of the HPCT clones lack carrier-mediated uptake of
      glycocholate and taurocholate. The clones which possess cholate transport are
      sensitive to phalloidin and take up bumetanide. In higher cell passages cholate
      transport and the sensitivity to phalloidin are reduced. This process is not
      prevented by a selection procedure with HAT-medium, nor is it stimulated by
      nicotinamide, dimethyl sulfoxide, or sodium butyrate. The cells of the 1E3, 1F9
      and 2E9 clones, but not Fao hepatoma cells synthesize bile acids endogenously
      even after 60 passages, and conjugate exogenously added cholate with taurine and
      glycine. These results indicate that liver-specific properties of freshly
      isolated hepatocytes which are lacking in the parental hepatoma cells are
      maintained in HPCT cells.

PMID- 7813522
TI  - Nongenotoxic carcinogens shift cultured rat hepatocytes into G1 cell cycle phase:
      influence of tissue oxygen tension on cells with different ploidy.
AB  - The transition of quiescent freshly isolated rat hepatocytes (G0 phase) into a
      prereplicative stage of the cell cycle (G1 phase) has been visualized by a
      decrease in fluorescence of quinacrine dihydrochloride (QDH)-stained nuclei. This
      transition might be used as an early detectable and sensitive marker for the
      identification of chemicals with a mitogenic potential. This was tested with
      three presumedly nongenotoxic carcinogens in the rodent, namely cyproterone
      acetate (CPA), thioacetamide (TA) and phenobarbital (PB). Freshly isolated
      hepatocytes were cultured under 13% or 4% O2, representing the tissue oxygen
      tension in the periportal (13% O2) and the pericentral area (4% O2) in the liver
      lobules. Fluorescence intensities of QDH-stained hepatocyte nuclei of different
      ploidy levels (2N, 4N or 8N) were quantified by image analysis. The epidermal
      growth factor induced G0-G1 shift was affected by the oxygen tension and was
      reversible as shown after exposure to retinoic acid (RA). At subtoxic
      concentrations, all three nongenotoxic carcinogens induced a shift of quiescent
      hepatocytes of all ploidy levels into the G1 cell cycle phase within a 6-h
      period. CPA was the most effective compound, followed by PB and TA. The strongest
      induction of the G0-G1 shift was observed in most cases in 2N nuclei. The oxygen
      tensions applied and the individual compounds tested, differentially affected the
      response of the individual ploidy classes. The results correspond well with the
      site-specific mitogenic response within liver lobules as observed after exposure
      in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7813523
TI  - Hans Berger (1873-1941).

PMID- 7813524
TI  - Adolescence and paediatrics in Europe.
AB  - Adolescence is an important period of growth and development. It is often claimed
      that adolescent care and assistance should be assigned to paediatricians who have
      followed children during their growth, are prepared to deal with growth and
      puberty problems, and are used to discussing with parents problems related to
      school, sports and habits. There is serious doubt as to the extent to which this
      actually occurs. An inquiry in various European countries demonstrates that there
      are wide differences in adolescent care and guidelines. Useful viewpoints for
      planning have emerged from the inquiry.

PMID- 7813526
TI  - Aldosterone-secreting adrenal cortical adenoma in an 11-year-old child and
      collective review of the literature.
AB  - We report a rare case of primary hyperaldosteronism due to a unilateral adrenal
      cortical adenoma in an 11-year-old female patient. The patient presented with
      hypertension, hypokalaemia and metabolic alkalosis, associated with inappropriate
      kaliuresis. The diagnosis was supported by the following laboratory findings:
      elevated plasma aldosterone, suppressed plasma renin activity, nonsuppressible
      aldosterone secretion following saline infusion and absent plasma aldosterone
      response to ambulation. MRI revealed a 1 cm-diameter adrenal tumour on the left
      side. Even though the NP-59 scintigraphy showed the negative result, laparotomy
      with left adrenalectomy was performed. Pathological examination confirmed an
      adenoma in the adrenal cortex. The patient's blood pressure and biochemical
      laboratory data normalized postoperatively within 2 days. We recommend that in
      hypertensive children with hypokalaemia and metabolic alkalosis, primary
      aldosteronism should be considered.

PMID- 7813525
TI  - Asplenia syndrome and isolated total anomalous pulmonary venous connection in
      siblings.
AB  - We report on a family with asplenia syndrome in one and total anomalous pulmonary
      venous connection (TAPVC) in the other sib. Both conditions are rare, may have a
      genetic cause and belong to a spectrum of laterality disorders. This suggests
      that both asplenia syndrome and TAPVC in this family are the clinical expression
      of a single genetic disorder.

PMID- 7813527
TI  - Fatal parathyroid hormone-related protein-induced humoral hypercalcemia of
      malignancy in a 3-month-old infant.
AB  - Parathyroid hormone-related protein (PTHrP) is the factor responsible for the
      syndrome of humoral hypercalcemia of malignancy (HHM). The syndrome is well
      documented in adult cancer patients, but has not previously been described in
      young children. We report the case of a 3-month-old infant who developed
      refractory hypercalcemia (peak total calcium 13.8 mg/dl; normal 8.5-10.5, ionized
      calcium 3.3 meq/l; normal 2.0-2.5) associated with a high-grade, poorly
      differentiated malignant hepatic sarcoma. Parathyroid hormone (intact) levels
      were suppressed (7.5 pg/ml; normal 10-65). Fractional excretion of phosphate was
      markedly elevated (73.5%; normal 8%-20%) as were urinary cAMP levels (12.48
      nmol/dl glomerular filtrate; normal 1.83-4.47) suggesting a PTH-like effect.
      Increased levels of PTHrP were present both in the serum (4.9 pmol/l; normal for
      adults < 1.5) and ascitic fluid (6.1 pmol/l). Since previous studies have
      demonstrated a potential role for PTHrP in the regulation of embryonal tissue
      differentiation and transmembrane calcium flux, our observation of elevated PTHrP
      levels associated with the development of a poorly differentiated hepatic sarcoma
      in a young infant may provide insight into the molecular mechanisms underlying
      HHM. We suggest that serum or plasma PTHrP levels be determined in all children
      with hypercalcemia of malignancy in whom the hypercalcemia cannot otherwise be
      explained.

PMID- 7813528
TI  - Percutaneous transjugular intrahepatic stent shunt for treatment of intractable
      varicose bleeding in paediatric patients.
AB  - Two 10-year and 11-year-old children with oesophageal and gastric varicose
      haemorrhage unresponsive to medical treatment and repeated endoscopic
      sclerotherapy underwent percutaneous transjugular intrahepatic portosystemic
      shunting (TIPSS). A newly developed introducing system was used. The procedure
      was performed to avoid the increased risk of emergency liver transplantation in
      children with hepatic failure. Immediately after the procedure bleeding stopped
      and the patient's condition improved. Ascites disappeared and liver function
      improved. The stent shunt was shown to be patent by angiography and Doppler
      ultrasound for a follow up period of more than 1 year. CONCLUSION: TIPSS may be
      of benefit in children with severe portal hypertension. It allows control of
      intractable bleeding, and stabilizes the patients preparing them for subsequent
      elective orthotopic liver transplantation.

PMID- 7813529
TI  - Longitudinal growth and final height in long-term survivors of childhood
      leukaemia.
AB  - Survival of children with acute lymphoblastic leukaemia (ALL) has increased
      considerably in recent years and data on the spontaneous growth and final height
      of these children are conflicting. Therefore, we analysed the longitudinal growth
      and final height in 52 survivors (33 females, 19 males) of childhood ALL. These
      children were diagnosed and treated in a single institution, all remained in
      first remission and were submitted to cranial irradiation with either 2400 or
      1800 cGy. None of the patients received testicular or spinal irradiation. Median
      age at diagnosis was 4.2 (range 1.3-9.6) years in the first group (2400 cGy) and
      3.9 (0.8-10.5) years in the second (1800 cGy). Standing height was measured at
      diagnosis, at the end of treatment (median 3.1 years after diagnosis), 6, 12, 24
      months after the end of treatment, and finally at the completion of growth. In
      girls a significant decrease of mean height standard deviation score (SDS) during
      treatment and a catch up in growth after the end of therapy was followed by a
      second period of reduced growth. Mean final height SDS was significantly lower
      than the value at diagnosis in both groups of girls, but only in males treated
      with 2400 cGy. Mean overall loss in height SDS from diagnosis to final height was
      higher in females (-1.24) than in males (-0.40) (P = 0.009). Females < or = 4
      years of age at diagnosis showed a higher loss in final height than females > 4
      years.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7813530
TI  - Hemidystonia secondary to acquired toxoplasmosis in a non-immunodeficient
      patient.
AB  - We discuss the unusual presentation of acquired toxoplasmosis in a girl with
      severe and transient hemidystonia as a unique symptom. Serum titres of anti
      toxoplasma antibodies increased whereas no specific antibody response in the CSF
      was observed. While symptomatic drugs were inefficacious, specific anti
      toxoplasmosis therapy led to complete and permanent recovery within 2 months.

PMID- 7813531
TI  - Monoclonal proliferation of Epstein-Barr virus-infected T-cells in a patient with
      virus-associated haemophagocytic syndrome.
AB  - Virus-associated haemophagocytic syndrome (VAHS) is a non-neoplastic, generalized
      histiocytic proliferation disorder showing marked haemophagocytosis associated
      with systemic viral infection. We describe the case of a 1-year-old girl with
      Epstein-Barr virus (EBV)-related VAHS, in whom Southern blot analysis showed
      monoclonal proliferation of bone marrow cells with the EBV genome; detected with
      the Xho-1 fragment of the latent infection membrane protein genome. EBV serology
      showed anti-Epstein-Barr virus nuclear associated antigen (EBNA), anti-viral
      capsid antigen (VCA)-IgG, anti-VCA-IgA elevation and positive EBNA of Sheep red
      blood cells (SRBC)-rosette-forming bone marrow cells in the late period of her
      clinical course, indicative of EBV infection. DNA analysis of her bone marrow
      cells showed monoclonal rearrangement of the T-cell receptor-beta and -gamma
      chain genes but not of the immunoglobulin heavy chain genes. Those results
      suggest that EBV may infect T-cells, after which the cells proliferate
      monoclonally. Repeated administration of epipodophyllotoxin VP-16-213 induced
      remission, but adrenocortical steroid, vincristine, and cyclophosphamide had no
      effect on the patient's condition. Ours is a first case report of VAHS showing
      monoclonal proliferation of EBV-infected T-cells.

PMID- 7813532
TI  - Eosinophils and eosinophil cationic protein in children with and without
      sensitization to inhalant allergens.
AB  - Eosinophil inflammation is a common feature of allergic disorders and
      particularly in allergic asthma interest has been paid to related markers. In a
      community-based survey of 10-year-old children, the association of eosinophil
      count (EC) and serum eosinophil cationic protein (ECP) with allergic
      sensitization, clinical history and exposure to mite allergen was studied.
      Relying on the results of skin prick tests, the children were divided to three
      groups: (1) children showing no sensitization to one of the seven inhalant
      allergens (n = 16); (2) children with sensitization to at least one of five non
      mite allergens (n = 16); and (3) children with sensitization to mite allergens (n
      = 75). Clinical history of asthma and hay fever was ascertained using
      standardized questionnaires. EC in peripheral blood and serum ECP were measured
      on one single occasion. Prior to blood sampling, mite allergen exposure at home
      had been assessed by taking dust samples and measuring the mite antigen
      concentration by means of an enzyme immunoassay. Compared to group 1, higher ECs
      were obvious in group 2 (P = 0.037) and in group 3 (P = 0.0013). Regarding serum
      ECP, higher levels occurred in group 2 (P = 0.0033) as well as in group 3 (P =
      0.0001) when comparing them to the reference group. Sensitized children with
      neither asthma, nor asthma-like symptoms, nor hay fever (n = 28) did not have
      significantly lower ECs and serum ECP levels than those with hay fever (n = 15; P
      = 0.09, P = 0.17) and those with asthma (n = 22; P = 0.69, P = 0.64).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7813533
TI  - Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: a severe fatty acid
      oxidation disorder.
AB  - 3-Hydroxyacyl-CoA dehydrogenase deficiency is a newly recognised fatty acid
      oxidation disorder with a usually fatal outcome. We present a further patient who
      presented with hypoketotic hypoglycaemia, hepatopathy, secondary carnitine
      deficiency and increased plasma long-chain acylcarnitines. 3-Hydroxydicarboxylic
      aciduria was present and the diagnosis confirmed in cultured skin fibroblasts.
      Our patient is compared with those reported in the literature with respect to
      clinical symptoms, differential diagnosis and possible therapeutic regimens.

PMID- 7813535
TI  - Povidone-iodine in umbilical cord care interferes with neonatal screening for
      hypothyroidism.
AB  - Out of 1346 newborns screened for congenital hypothyroidism, 31 non-hypothyroid
      infants were summoned because of a thyroid stimulating hormone (TSH) level above
      10 microU/ml. False-positive TSH levels were significantly more frequent in the
      babies treated with povidone-iodine (4.6%) than in those treated with either
      alcohol or triple dye (0.7%). CONCLUSION. Iodine containing solutions should be
      avoided in umbilical cord care of the newborn.

PMID- 7813534
TI  - Cyclic variation pattern of cerebral blood flow velocity and postconceptional
      age.
AB  - In preterm neonates, the risk for intracerebral haemorrhage is linked to
      immaturity of cerebral autoregulation. The preterm's 2-5/min cyclic variation
      pattern of cerebral blood flow velocity is thought to reflect the degree of
      immaturity of autoregulation--a speculation to be tested. In a cross-sectional
      study 15 infants (gestational age 26-40 weeks, postconceptional age (PCA) 26-42
      weeks, age 1-99 days were investigated. We performed a 10 min pulsed Doppler
      tracing on an internal carotid artery by means of a computer controlled 5 MHz
      Duplex device. Systolic velocity (Vs) was recorded pulse by pulse. After
      appropriate data transformation, in all infants the Fast Fourier Transform of the
      time course of Vs revealed the presence of a 2-5/min cyclic variation pattern
      (one sample z-test, P < 0.0001). There was no significant correlation between
      proportionate spectral power of the 2-5/min frequency band and either PCA (r =
      0.23, P = 0.42) or age (r = 0.41, P = 0.13). Between 26 and 42 weeks PCA, the
      cycling phenomenon is constant thus not reflecting cerebral maturation, and its
      presence does not mean immaturity of cerebral autoregulation.

PMID- 7813536
TI  - Diffuse neonatal haemangiomatosis with intra-uterine haemorrhage and hydrops
      fetalis: a case report.
AB  - A case of diffuse neonatal haemangiomatosis involving the skin, liver, lungs,
      adrenals, gums, diaphragm, skull, and testes is reported. Intra-uterine onset of
      bleeding led to bloody amniotic fluid, severe anaemia, congestive heart failure,
      and hydrops fetalis. Intractable coagulopathy and renal failure resulted in
      persistent bleeding, anuria, metabolic acidosis, and hyperkalaemia, leading to a
      fatal outcome.

PMID- 7813537
TI  - High-dose intravenous immunoglobulin treatment in cryptogenic West and Lennox
      Gastaut syndrome; an add-on study.
AB  - In an add-on pilot study, a group of 15 children with cryptogenic and intractable
      West syndrome (3) and Lennox-Gastaut syndrome (12) received intravenous
      immunoglobulin (IVIg, 0.4 g/kg body weight per day for 5 consecutive days,
      followed by the same dose once every 2 weeks for 3 months). Five patients had
      been treated previously with ACTH without success. The reduction in clinical
      seizures averaged 70%. Electroencephalographic (EEG) recordings revealed a mean
      reduction in epileptic discharges of 40%. In all 15 patients, acceleration of EEG
      background activity occurred, and psychomotor development improved. Prior to IVIg
      administration, CSF examinations were normal. After IVIg administration, the
      serum total IgG concentration increased by an average of 76%, and the CSF IgG
      concentration by 44%. According to our data, IVIg crosses the blood-CSF barrier,
      and might be effective in the treatment of West syndrome and Lennox-Gastaut
      syndrome. We suggest it should be considered when other treatments, such as ACTH,
      have failed.

PMID- 7813539
TI  - Diagnostic value of ethylenediaminetetraacetic acid infusion in partial DiGeorge
      anomaly.

PMID- 7813538
TI  - Zinc and copper in infants fed breast-milk or different formula.
AB  - In 129 term infants at birth and at the age of 4 months, zinc and copper
      concentrations of plasma and urine were determined by graphite furnace atomic
      absorption spectrophotometry and the values correlated to other biochemical
      parameters and somatic data. Of the infants, 49 were exclusively breast-fed, 44
      fed with various commercially available cow's milk formula, 35 fed with a
      hypoallergenic formula (cows's milk whey hydrolysate, commercially available,
      supplemented with zinc and copper). Plasma zinc values declined from birth to the
      age of 4 months in all three groups (P < 0.001). In formula fed children, 4
      months old, the values (11.1 +/- 1.7 mumol Zn/l) were significantly lower than in
      breast-fed (12.2 +/- 1.7 mumol Zn/l; P = 0.004) or babies on hypo-allergenic
      formula (12.4 +/- 1.6 mumol Zn/l; P = 0.0015). In accordance with the literature
      plasma copper and caeruloplasmin values increased significantly within the first
      4 months of life, the plasma levels were similar in either feeding group, only
      urinary copper excretion was higher in male infants on hypo-allergenic formula (P
      < 0.03) at the age of 4 months. There were no correlations between zinc or copper
      values and alkaline phosphatase. In infants on hypo-allergenic formula there was
      a negative correlation between plasma zinc and weight or height increments.
      Despite different zinc and copper supply, presumedly different bioavailability,
      and different plasma zinc values, all infants thrived and weight and length
      increments were similar in each group.

PMID- 7813540
TI  - Megadose methylprednisolone treatment for malignant osteopetrosis.

PMID- 7813541
TI  - Ranitidine-induced bradycardia in a neonate--secondary to congenital long QT
      interval syndrome?

PMID- 7813542
TI  - 7-OH-DPAT produces place conditioning in rats.
AB  - The rewarding properties of the putative dopamine D3 receptor-selective agonist,
      7-OH-DPAT ((+/-)-2-dipropylamino-7-hydroxy-1,2,3,4- tetrahydronaphthalene
      hydrobromide), were investigated using a place conditioning paradigm consisting
      of three phases: preconditioning (three undrugged exposures to an apparatus
      consisting of two visually distinct compartments); conditioning (four pairings of
      one compartment with drug); and test (one undrugged exposure to the same
      apparatus). Rats received either saline, amphetamine (2.0 mg/kg), or 7-OH-DPAT
      (0.5, 2.0 or 5.0 mg/kg) during conditioning. Amphetamine and 7-OH-DPAT produced a
      place preference.

PMID- 7813543
TI  - Localisation of dopamine D2-like receptors in pulmonary artery of the human and
      rabbit but not of the rat.
AB  - The present study was designed to investigate the presence of dopamine D2-like
      receptor sites in the main trunk of the human, rabbit and rat pulmonary artery
      using combined radioligand binding and light microscope autoradiography
      techniques. [3H]Spiroperidol was used as a ligand. The presence and the
      localisation of the sympathetic neuroeffector plexus were also studied using
      catecholamine histofluorescence techniques. Radioligand binding experiments
      demonstrated the labelling of a population of dopamine D2-like receptors in
      sections of human and rabbit pulmonary arteries by [3H]spiroperidol. No specific
      binding occurred in sections of the rat pulmonary artery. Light microscope
      autoradiography showed the development of specific silver grains within the
      tunica adventitia, including the adventitia-media border, of the human and rabbit
      pulmonary arteries. No specific silver grains were found in sections of the rat
      pulmonary artery. Studies on the pharmacological characterisation of
      [3H]spiroperidol binding sites in the human and rabbit pulmonary arteries showed
      that they are sensitive primarily to domperidone, haloperidol, (-)-sulpiride or
      bromocriptine, and to a lesser extent to n-propylnorapomorphine, quinpirole or
      clozapine displacement. This suggests that [3H]spiroperidol binding sites in the
      pulmonary artery probably belong to the dopamine D2 receptor subtype.
      Catecholamine histofluorescence techniques revealed a rich plexus of fluorescent
      adventitial and adventitial-medial nerve fibres in the human and to a lesser
      extent in the rabbit pulmonary artery. Comparison of the localisation of dopamine
      D2-like receptor sites and of the sympathetic neuroeffector plexus in the
      pulmonary artery, suggests a possible prejunctional localisation of these sites.

PMID- 7813545
TI  - Block of Na+ channel by moricizine hydrochloride in isolated feline ventricular
      myocytes.
AB  - The effect of moricizine hydrochloride, a potent class I antiarrhythmic agent, on
      Na+ current (INa) of single feline ventricular myocytes were studied using whole
      cell patch clamp techniques. Moricizine inhibited INa in a concentration
      dependent manner without altering the current-voltage relationship for INa. INa
      inhibition was expressed by the Hill equation with a Hill coefficient of 1.3 and
      dissociation constant of 105 microM in the resting state (holding potential = 
      140 mV). Moricizine 30 microM shifted the steady state inactivation curve for INa
      toward more negative potentials by 7.3 +/- 2.4 mV without causing significant
      changes in the slope factor. Recovery of INa from inactivation was retarded (time
      constant = 8 s) at a holding potential of -140 mV in the presence of 30 microM
      moricizine. When the start of INa block was studied in experiments using a double
      pulse protocol, moricizine reduced INa by only 4% after a 4-ms prepulse, but
      strongly inhibited it after prepulses longer than 200 ms. Intracellular
      application of 100 microM moricizine did not produce significant resting or use
      dependent INa block. These results suggest that (1) moricizine blocks INa by
      binding to the Na+ channel with a 1:1 stoichiometry, (2) the drug has a higher
      affinity to the inactivated state than to the activated and resting states of the
      Na+ channel, (3) recovery kinetics of moricizine from Na+ channel inactivation,
      or drug dissociation observed during the transition from inactivated to resting
      state was relatively slow, (4) the drug binding site appeared to be located on
      the external side of the membrane.

PMID- 7813546
TI  - The CCKB receptor antagonist, L-365,260, elicits antidepressant-type effects in
      the forced-swim test in mice.
AB  - Selective CCKA and CCKB receptor agonists and antagonists were used to study the
      involvement of endogenous cholecystokinin in the behavioural changes that occur
      in mice in the forced-swimming test (Porsolt's test). The CCKB receptor
      antagonist, L-365,260 ((3R)-(+)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-
      benzodiazepin-3-yl)-3-methylphenylurea), but not the CCKA receptor antagonist,
      devazepide ((3S)-(-)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepin 
      3-yl)- 1H-indole-2-carboxamide), elicited an antidepressant-type response (a
      decrease in the duration of immobility) that was suppressed by previous treatment
      with either CCK-8 (H-Asp-Tyr(OSO3H)-Met-Gly- Trp-Met-Asp-Phe-NH2) or the
      selective CCKB receptor agonist BC-264 (Boc-Tyr(SO3H)-gNle-mGly-Trp-N(Me)-Nle-Asp
      Phe- NH2). The L-365,260 effect was also prevented by the dopamine receptor
      antagonist, SCH-23,390 (a dopamine D1-selective receptor antagonist: R(+)-7
      chloro-8-hydroxy-3-methyl-1-phenyl- 2,3,4,5-tetrahydro-1H-3-benzazepine) and
      sulpiride (a dopamine D2-selective receptor antagonist: (-)-5-(aminosulfonyl)-N
      [(1-ethyl-2-pyrrolidinyl) methyl]-2-metoxybenzamide). On the other hand, co
      administration of subthreshold doses of L-365,260 and nomifensine (an atypical
      antidepressant that selectively blocks dopamine re-uptake mechanisms, 1,2,3,4
      tetrahydro-2-methyl-4-phenyl-8-isoquinolinamine) led to a potent antidepressant
      type response. These results indicate that blocking of CCKB receptors could
      result in an increase of extracellular dopamine contents in some brain areas
      involved in depression and suggest a potential use of CCKB receptor antagonists,
      alone or combined with antidepressants, in the treatment of depressive syndromes.

PMID- 7813544
TI  - Pro-inflammatory and anti-inflammatory effects of the stable prostaglandin D2
      analogue, ZK 118.182.
AB  - This study examined the pro- and anti-inflammatory effects of the stable
      prostaglandin (PG) D2 analogue, ZK 118.182 and the mechanism by which
      prostaglandins may exert their anti-inflammatory activity. Co-injected locally,
      ZK 118.182, like PGE2 and PGD2, dose-dependently increased plasma leakage induced
      by intradermal injection of bradykinin in rabbit skin. Infused i.v., ZK 118.182
      (0.45 microgram/kg/min), a dose which did not affect systemic blood pressure,
      inhibited oedema formation in rabbit skin induced by the neutrophil-dependent
      agonists, formyl-methionyl-leucyl-phenylalanine (FMLP) and leukotriene B4 (LTB4).
      However, it did not modify plasma leakage induced by the neutrophil-independent
      mediators, bradykinin and platelet-activating factor (PAF). In contrast,
      neutrophil accumulation in response to LTB4 and FMLP was not affected in animals
      infused with ZK 118.182. In vitro, ZK 118.182, like PGE2 and PGD2 inhibited FMLP
      induced superoxide anion (O2-) production by rabbit neutrophils. The compound,
      however, had minimal effects on O2- production induced by phorbol myristate
      acetate (PMA). ZK 118.182 inhibited to a small extent FMLP but not PMA-induced
      neutrophil adherence. These results show that depending on the route of
      administration, the PGD2 analogue, ZK 118.182, exhibits either pro- or anti
      inflammatory effects. The anti-inflammatory effect may be related to the ability
      of the compound to inhibit increased microvascular permeability induced by
      neutrophil activation without interfering with neutrophil accumulation. This
      latter effect may be due to the analogue's capacity to suppress neutrophil
      secretion to a greater extent than neutrophil adherence.

PMID- 7813547
TI  - Role of platelet activating factor in acute pancreatitis induced by
      lipopolysaccharides in rabbits.
AB  - In the present study we demonstrated that a single injection of endotoxin
      (lipopolysaccharides, E. Coli 0111-B4) into the superior pancreaticoduodenal
      artery of rabbits induced a dose-dependent acute necrotizing pancreatitis. The
      lesions observed by light microscopy were significant for 10 micrograms
      lipopolysaccharides and were maximal for 20 micrograms. After 24 h the main
      findings were edema, acinar cell vacuolisation, polymorphonuclear neutrophil
      infiltration and tissue necrosis. The pancreatic lesions developed strictly in
      the area supplied by the artery injected with lipopolysaccharides, without
      significant intestinal involvement. Since platelet-activating factor (1-O
      hexadecyl-2-acetyl-sn-glycero-3- phosphocholine, PAF; 50-500 ng), a phospholipid
      mediator of endotoxin-induced inflammation and shock, was previously shown to
      cause an acute necrotizing pancreatitis in rabbits, the role of PAF in the
      development of acute pancreatitis induced by lipopolysaccharides was studied by
      evaluating: (1) the synergism between doses of lipopolysaccharides (5-10
      micrograms), which produced a mild tissue injury, and doses of PAF (10 ng) not
      producing, per se, any significant injury, and (2) the effect of three
      structurally unrelated PAF receptor antagonists. The results obtained
      demonstrated that 10 ng of PAF significantly potentiated pancreatic tissue damage
      induced by 10 micrograms of lipopolysaccharides.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7813548
TI  - Evidence for the presence of two types of P2 purinoceptor in the guinea-pig ileal
      longitudinal smooth muscle preparation.
AB  - The effects of some agonists acting at P2 purinoceptors on guinea-pig isolated
      ileum longitudinal smooth muscle have been examined. The preparation contracted
      in response to ATP, alpha,beta-methylene ATP and 2-methylthio ATP, but not UTP.
      In this respect, alpha,beta-methylene ATP and 2-methylthio ATP were approximately
      equipotent and both were 10-50 times more active than ATP. Responses to
      alpha,beta-methylene ATP, but not 2-methylthio ATP or ATP, were antagonised by
      atropine and tetrodotoxin, suggesting that alpha,beta-methylene ATP activates
      cholinergic nerves in the ileum, whilst the other two compounds act on the smooth
      muscle. Two other purine nucleotide analogues, beta,gamma-methylene ATP and
      beta,gamma-imido ATP, did not cause contraction. However, both compounds
      antagonised responses to alpha,beta-methylene ATP, but not those to 2-methylthio
      ATP. Suramin antagonised responses to both alpha,beta-methylene ATP and 2
      methylthio ATP, whilst Cibacron blue was without effect on responses to either
      agonist. We conclude that the purinoceptor on cholinergic nerves has some of the
      characteristics of the P2x purinoceptor, whilst the purinoceptor on ileal smooth
      muscle has some of the characteristics of the P2Y purinoceptor. However, further
      work will be necessary before definitive classification is possible.

PMID- 7813549
TI  - Human endothelin ETA receptor antisense oligodeoxynucleotides inhibit endothelin
      1 evoked vasoconstriction.
AB  - Antisense oligodeoxynucleotides to endothelin ETA receptor mRNA were used to
      characterize vascular smooth muscle receptors. The concentration-response curve
      showed a significant attenuation of endothelin-1-induced contraction in circular
      segments of the human superficial temporal artery. Endothelin ETB receptor
      antisense or mismatch oligodeoxynucleotides showed no alteration of the
      endothelin-1-induced contraction. Complementary experiments with the selective
      endothelin ETA receptor antagonist FR139317 demonstrated a shift of the
      concentration-response curve to the right in a competitive manner (pA2 = 6.93).
      The specific method of using the receptor antisense oligodeoxynucleotides
      approach revealed the presence of endothelin ETA receptors mediating contraction
      in the human superficial temporal artery.

PMID- 7813550
TI  - Preclinical pharmacology of FG5893: a potential anxiolytic drug with high
      affinity for both 5-HT1A and 5-HT2A receptors.
AB  - The effects of FG5893 were evaluated by several different methods; rats were used
      as experimental animals. Receptor binding studies revealed that FG5893 (2-(4-(4,4
      bis(4-fluorophenyl)butyl)-1-piperazinyl)-3-pyridinecarboxy lic acid methyl ester)
      binds with high affinity to both 5-HT1A (Ki = 0.7 nM) and 5-HT2A receptors (Ki =
      4.0 nM) but has only low affinity for the 5-HT2C receptor (Ki = 170 nM). FG5893
      dose dependently reduced body temperature, and this effect was inhibited by
      pretreatment with (+/-)-pindolol. FG5893 (0.1 mg/kg) significantly inhibited head
      twitch behaviour induced by DOI (1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane)
      and FG5893 was also a potent inhibitor of ultrasound vocalization in rat pups
      (0.3 mg/kg) and of a passive avoidance response (0.1 mg/kg) in mature animals.
      FG5893 inhibited the cage-leaving response and induced part of the 5-HT
      behavioural syndrome, but only at very high doses (5 and 10 mg/kg, respectively).
      At increased doses (1 mg/kg), FG5893 also elicited corticosterone release and
      reduced the immobility time in the forced-swim test (1 mg/kg). Together, these
      data indicate that the mixed 5-HT1A receptor agonist/5-HT2A receptor antagonist
      FG5983 is a potent stimulator of presynaptic 5-HT1A receptors but is less active
      at the postsynaptic site. FG5893 had potent anxiolytic-like effects both on
      separation-induced ultrasound vocalization in rat pups and on a passive avoidance
      response. At increased doses, FG5893 possessed an antidepressant-like property.

PMID- 7813551
TI  - 1-Aminocyclopropanecarboxylic acid protects against dynorphin A-induced spinal
      injury.
AB  - Lumbar subarachnoid injection of dynorphin A causes an ischemia-induced neuronal
      degeneration and persistent hindlimb paralysis. The protective effects of a
      variety of competitive and non-competitive N-methyl-D-aspartate (NMDA) receptor
      antagonists indicate that activation of the NMDA receptor complex is essential
      for dynorphin A-induced spinal cord injury. 1-Aminocyclopropanecarboxylic acid
      (ACPC) is a high affinity, partial agonist at strychnine-insensitive glycine
      receptors associated with the NMDA receptor complex. Pretreatment of rats with
      ACPC (100 and 200 mg/kg, i.p., 30 min prior to dynorphin A) significantly
      eliminated the persistent hindlimb motor deficits and neuropathological changes
      produced by 20 nmol of this peptide. The neuroprotective effects of ACPC (100
      mg/kg, i.p.) were abolished by parenteral administration of glycine (800 mg/kg,
      30 min prior to ACPC), consistent with other in vivo and in vitro studies
      indicating that the pharmacological actions of ACPC are effected through
      strychnine-insensitive glycine receptors. When given instead as six daily
      injections (200 mg/kg, i.p.) followed by an injection-free day, ACPC also
      significantly improved neurological recovery following dynorphin-A injection.
      These results support earlier indications that: (1) activation of the NMDA
      receptor complex plays a critical role in mediating dynorphin A-induced rat
      spinal cord injury; (2) ACPC provides an effective means of antagonizing
      excitotoxic phenomena; and (3) chronic administration of ACPC can elicit a
      persistent change in the NMDA receptor complex.

PMID- 7813552
TI  - An electrophysiological basis for the antiarrhythmic actions of the kappa-opioid
      receptor agonist U-50,488H.
AB  - This study examined the actions of the selective kappa-opioid receptor agonist, U
      50,488H, on voltage activated Na+ and K+ currents in isolated rat cardiac
      myocytes. U-50,488H produced a concentration-dependent block of the transient Na+
      current with an ED50 of about 15 microM, and, at higher concentrations (40-50
      microM), a block of the plateau K+ current and an increase in the rate of decay
      of the transient K+ current. In addition U-50,488H produced a hyperpolarising
      shift in the inactivation curve for the transient Na+ current without altering
      the voltage dependence for activation and without an effect on the voltage
      dependence of inactivation or activation of K+ currents. The block of Na+
      currents by U-50,488H showed pronounced use dependence. The kappa-opioid receptor
      antagonist MR2266 did not itself produce any change in the Na+ or K+ currents and
      did not change the channel blocking properties of U-50,488H. Thus, since the
      antiarrhythmic actions of U-50,488H are not blocked by MR2266 or naloxone, the
      effects of U-50,488H to block Na+ and K+ currents are the most likely reasons for
      its antiarrhythmic actions, rather than an action at kappa-opioid receptors.

PMID- 7813553
TI  - Heterogeneity of prejunctional neuropeptide Y receptors inhibiting noradrenaline
      overflow in the portal vein of freely moving rats.
AB  - The effects of intraportal infusions of different doses of neuropeptide Y, its
      selective neuropeptide Y Y1 receptor analogue, [Leu31,Pro34]neuropeptide Y, and
      the Y2-selective C-terminal fragment, neuropeptide Y-(18-36), on basal and
      electrically evoked noradrenaline overflow in the portal vein as well as on mean
      arterial pressure and heart rate were investigated in permanently instrumented
      freely moving rats. Neuropeptide Y dose dependently (2-2000 ng/kg/min) attenuated
      the electrically evoked noradrenaline overflow and almost complete blockade was
      reached at the highest dose used. [Leu31,Pro34]Neuropeptide Y also dose
      dependently (20-20,000 ng/kg/min) attenuated the evoked overflow, reaching a
      maximum of 55% inhibition at the highest dose (20,000 ng/kg/min). Neuropeptide Y
      (18-36) attenuated the evoked release only at 20,000 ng/kg/min (by 46%). Only at
      the highest dose did neuropeptide Y (2000 ng/kg/min) and
      [Leu31,Pro34]neuropeptide Y (20,000 ng/kg/min) significantly enhance mean
      arterial pressure and decrease heart rate and basal plasma noradrenaline levels,
      the latter two effects being due to the baroreceptor reflex. Neuropeptide Y-(18
      36) did not influence these parameters at all doses used. The results indicate
      the presence of prejunctional neuropeptide Y Y1 receptors, and possibly the
      coexistence of Y1 and Y2 receptors, in the portal vein of freely moving rats,
      which in conjunction are able to inhibit markedly electrically evoked
      noradrenaline overflow. Postjunctional neuropeptide Y receptors mediating an
      increase in blood pressure in the freely moving rat are solely of the Y1 subtype.

PMID- 7813554
TI  - Neurosteroids in the brain of handling-habituated and naive rats: effect of CO2
      inhalation.
AB  - In rats habituated to the manipulation that precedes killing (handling
      habituated) the cerebral cortical concentrations of pregnenolone and progesterone
      were significantly lower (-57% and -69%, respectively) than in naive animals. An
      acute stress, induced by CO2 inhalation, elicited a marked increase in the
      concentrations of pregnenolone, progesterone and deoxycorticosterone in the brain
      cortex and hippocampus of handling-habituated rats. An accepted stress, such as
      foot shock, also enhanced the brain cortical levels of pregnenolone, progesterone
      and deoxycorticosterone in handling-habituated rats. These data show that the rat
      brain cortical and hippocampal steroid content is related to the 'emotional
      state' of the animal.

PMID- 7813555
TI  - Anxiolytic-like effect of (S)-WAY 100135, a 5-HT1A receptor antagonist, in the
      murine elevated plus-maze test.
AB  - The effects of (S)-WAY 100135 ((S)-N-tert-butyl-3-(4-(2-methoxyphenyl)- piperazin
      1-yl)-2-phenyl-propanamide dihydrochloride; 2.5-20.0 mg/kg), a 5-HT1A receptor
      antagonist, on the behaviour of male mice were examined in the elevated plus-maze
      test of anxiety. An ethological scoring technique was used to provide a
      comprehensive profile of drug action. Only minor changes in behaviour were
      observed at 2.5 and 5.0 mg/kg, and consisted of reductions in some (though not
      all) risk assessment measures. At 10 mg/kg, the compound increased percent open
      arm entries and percent open arm time, without altering general activity levels.
      This classic anxiolytic-like profile was confirmed by major reductions in risk
      assessment measures including protected head-dips and protected stretched attend
      postures. Although many of the same changes were also observed at 20 mg/kg, the
      absence of an effect on percent open arm time and a tendency towards increased
      non-exploratory behaviour suggested (1) some loss of anxiolytic activity and (2)
      a possible contribution of non-specific factors at higher doses. Present findings
      indicate that (S)-WAY 100135 produces clear anxiolytic-like effects in the murine
      elevated plus-maze, a profile that can be distinguished from that produced by 5
      HT1A receptor partial agonists in the same test.

PMID- 7813556
TI  - Dopamine D2 and D3 receptor preferring antagonists differentially affect striatal
      dopamine release and metabolism in conscious rats.
AB  - Classical neuroleptic drugs with high affinity for dopamine D2 receptors in
      comparison to D3 ones (haloperidol, thioproperazine and spiperone) administered
      i.p. acutely (0.2, 0.2 and 0.07 mg/kg, respectively) induced a pronounced
      increase in the extracellular level of 3,4-dihydroxyphenylacetic acid (DOPAC) and
      only a modest rise in that of dopamine in the dorsal striatum of conscious rats
      studied by transcerebral microdialysis. Atypical neuroleptics, clozapine and
      thioridazine (both 20 mg/kg), demonstrating relatively higher affinity for
      dopamine D3 receptor than typical ones, as well as the dopamine D3 receptor and
      autoreceptor preferring antagonists, cis-(+)-(1S,2R)-5-methoxy-1-methyl-2-(di-n-
      propylamino)tetralin HCl ((+)-UH232) and cis-(+)-(1S,2R)-5-methoxy-1-methyl-2-(n
      propylamino)tetralin HCl ((+)-AJ76) (both 14 mg/kg), were equally effective or
      even more potent in increasing dopamine release than DOPAC. It is concluded that
      the dopamine D2/D3 receptor relative potencies of typical and atypical
      neuroleptics appear to correspond to their ability to affect preferentially
      dopamine metabolism or release in rat dorsal striatum in vivo.

PMID- 7813557
TI  - Somatostatin-induced inhibition of neurotransmission in the mouse isolated vas
      deferens is resistant to pertussis toxin.
AB  - The potential effects of pertussis toxin pretreatment on the inhibitory effect of
      somatostatin (SRIF) and the selective SRIF receptor agonist, seglitide, were
      studied in mouse vas deferens and these were compared with its effect on the
      negative chronotropic action of carbachol in mouse atria. Somatostatin and
      seglitide caused a concentration-dependent inhibition of neurogenically mediated
      contractile responses in the vas deferens (EC50 values of 15 and 0.6 nM
      respectively). There was no difference in their potencies in preparations removed
      from pertussis toxin pretreated mice. In contrast, the negative chronotropic
      action of carbachol in mouse atria was abolished by pretreatment with pertussis
      toxin. We conclude that, in contrast to muscarinic receptor activation in mouse
      atria, the inhibitory effect of somatostatin in the vas deferens is not mediated
      by a pertussis toxin sensitive G-protein. The high potency of seglitide suggests
      that the SRIF receptor involved is of the SRIF1 type.

PMID- 7813558
TI  - Profiles of emetic action of cisplatin in the ferret: a potential model of acute
      and delayed emesis.
AB  - The emetic profile of action of cisplatin 5 and 10 mg/kg i.p. was investigated in
      the ferret over a 72 and 40 h period respectively. Cisplatin 10 mg/kg induced
      retching and vomiting which rapidly declined after the first 8 h. Cisplatin 5
      mg/kg induced a less intense emetic response which declined after 16 h but
      reappeared at approximately 32 h to reveal a 'delayed' retching and vomiting
      response. The use of cisplatin 5 mg/kg may offer a regimen to model cytotoxic
      acute and delayed emesis.

PMID- 7813559
TI  - NMDA redox site modulates long-term potentiation of NMDA but not of AMPA
      receptors.
AB  - We have compared the effects of redox drugs on long-term potentiation mediated by
      AMPA or NMDA receptors. A reducing and an oxidizing agent had no effect on long
      term potentiation mediated by AMPA receptors. In contrast, the induction of long
      term potentiation mediated by NMDA receptors was prevented by a thiol oxidizing
      drug and restored by a disulfide reducing agent.

PMID- 7813560
TI  - Differential dopaminergic regulation of the neurotensin striatonigral and
      striatopallidal pathways in the rat.
AB  - Recently the existence of a neurotensin striatonigral pathway strongly up
      regulated by methamphetamine has been demonstrated. The aim of the present study
      was to investigate, using immunohistochemistry and radioimmunoassay, the
      modulation of this pathway by dopamine antagonists. Rats were injected either
      with methamphetamine alone or together with the dopamine D1 receptor antagonist,
      SCH 23390 (R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-be
      nzapine hydrochloride), or with the dopamine D2 receptor antagonist, sulpiride.
      Both techniques showed that this neurotensin striatonigral pathway is regulated
      by dopamine D1 receptors, since SCH 23390 totally prevented the methamphetamine
      induced increase in neurotensin-like immunoreactivity, both in the striatum and
      in the substantia nigra pars reticulata. Conversely, sulpiride was unable to
      counteract the effect of methamphetamine in these two areas, suggesting that
      dopamine D2 receptors are not involved in the regulation of this neurotensin
      pathway. On the other hand, neurotensin-like immunoreactivity was markedly
      increased in striatal cell bodies and in the globus pallidus after treatment with
      sulpiride, indicating that this pathway is mainly regulated by dopamine D2
      receptors.

PMID- 7813561
TI  - Antidepressant-like effect of selective dopamine D1 receptor agonists in the
      behavioural despair animal model of depression.
AB  - We compared the effect of two selective dopamine D1 receptor agonists, SKF 38393
      ((+/-)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol.HCl) and A68930
      ((1R,3S)-1-aminomethyl-5,6-dihydroxy-3-phenylisochroman.HCl), and that of
      imipramine in the behavioural despair model of depression. The dopamine D1
      receptor agonists and imipramine showed an anti-immobility effect. Moreover we
      found that the 'antidepressant' effect of imipramine in the behavioural despair
      test was antagonized by SCH 23390, a selective dopamine D1 receptor blocker. The
      results further support the hypothesis that dopamine D1 receptor stimulation
      plays an important role in the mechanism of action of antidepressants and suggest
      that dopamine D1 receptor agonists might be considered as potential
      antidepressant drugs.

PMID- 7813562
TI  - DP-1904, a specific inhibitor of thromboxane A2 synthesizing enzyme, suppresses
      ICAM-1 expression by stimulated vascular endothelial cells.
AB  - Intercellular adhesion molecule-1 (ICAM-1) is an antigen that is strongly
      expressed by vascular endothelial cells at sites of local inflammation and
      participates in the development of inflammation. In the present study, vascular
      endothelial cells were stimulated by inflammatory cytokines that promote
      thromboxane A2 synthesis to observe their effects on the expression and shedding
      of ICAM-1 on the cell surface. In addition, the suppressive effects of DP-1904
      ([+/-]-6-[1-imidazolylmethyl]-5,6,7,8-tetrahydronaphthalene-2- carboxylic acid
      hydrochloride hemihydrate), a thromboxane A2 synthesis inhibitor, on ICAM-1
      expression were evaluated. ICAM-1 expression on the surface of human umbilical
      vein endothelial cells was increased significantly by stimulation with
      interleukin-1 beta, tumor necrosis factor alpha (TNF alpha), thrombin and
      platelet-activating factor (PAF). DP-1904, an inhibitor of thromboxane A2
      synthesis, significantly suppressed the expression of ICAM-1 on the surface of
      human vascular endothelial cells that had been stimulated by TNF alpha or PAF.
      These findings suggest that an enhanced expression of thromboxane A2 on human
      vascular endothelial cells is closely related to the expression of ICAM-1 on the
      surface of these cells.

PMID- 7813563
TI  - Chronic mianserin or eltoprazine treatment in rats: effects on the elevated plus
      maze test and on limbic 5-HT2C receptor levels.
AB  - Rats were chronically treated with mianserin (10 mg/kg i.p.) or eltoprazine (1
      mg/kg i.p.) and were tested in the elevated plus-maze test for anxiety. 5-HT2C
      (previously 5-HT1C, see Humphrey et al., 1993, Trends Pharmacol. Sci. 14, 223)
      binding sites and their mRNA were evaluated in limbic structures (i.e., amygdala,
      hippocampus, septum) of a sample of these rats by autoradiographic binding
      studies and in situ hybridization histochemistry. Mianserin and eltoprazine
      displayed opposite effects in the elevated plus-maze: mianserin induced
      anxiolytic-like effects, while eltoprazine showed anxiogenic-like ones. Within
      the amygdala, but not in other structures, the quantitative autoradiographic
      analysis of the 5-HT2C binding sites showed a differential effect: mianserin
      treatment induced a decrease in the number of these sites, while eltoprazine
      treatment resulted in an increase. In spite of this, neither mianserin- nor
      eltoprazine-treated rats displayed an alteration in the 5-HT2C receptor mRNA
      levels in the brain regions examined. Our results are suggestive of a relation
      between anxiolytic/anxiogenic-like effects and the level of 5-HT2C binding sites
      in the amygdala.

PMID- 7813564
TI  - The presence of islet amyloid polypeptide/calcitonin gene-related peptide/salmon
      calcitonin binding sites in the rat nucleus accumbens.
AB  - Receptor autoradiographic analysis of binding in rat brain sections for
      [125I]islet amyloid polypeptide (IAPP), [125I]calcitonin gene-related peptide
      (CGRP) and [125I]salmon calcitonin indicated dense binding for all three ligands
      in the nucleus accumbens. Membrane binding studies revealed the existence of high
      affinity sites for all three peptides. The order of potency of various related
      peptides at each binding site was investigated and found for [125I]IAPP to be
      salmon calcitonin > IAPP = alpha CGRP > salmon calcitonin-(8-32); for [125I]CGRP
      to be alpha CGRP > IAPP > salmon calcitonin; and for [125I]salmon calcitonin to
      be salmon calcitonin > alpha CGRP > rat calcitonin > salmon calcitonin-(8-32) >
      IAPP, suggesting that [125I]IAPP targets the CGRP3 receptor subtype. This study
      confirms the existence of two receptors in the rat nucleus accumbens binding
      salmon calcitonin, one of which binds alpha CGRP and IAPP with a high affinity.

PMID- 7813565
TI  - Antidepressant-induced modulation of GABAA receptors and beta-adrenoceptors but
      not GABAB receptors in the frontal cortex of olfactory bulbectomised rats.
AB  - The effects of prolonged administration of antidepressant drugs, belonging to
      three different classes, on high-affinity GABAA receptor, GABAB receptor and beta
      adrenoceptor binding parameters were determined in the frontal cortex of
      olfactory bulbectomised rats. Clorgyline (1 mg/kg/day), paroxetine (10 mg/kg/day)
      or desipramine (10 mg/kg/day) were administered for 21 days via subcutaneous
      osmotic minipumps implanted in the scapular region 7 days after bulbectomy.
      Cortical GABAA receptor densities, defined with [3H]gamma-aminobutyric acid
      ([3H]GABA), were significantly increased following bulbectomy. This effect on
      Bmax values was reversed by all three antidepressant drugs. GABAB receptor
      densities decreased slightly after bulbectomy. Chronic antidepressant
      administration had no effect on GABAB receptor binding parameters. Olfactory
      bulbectomy did not induce any changes in cortical beta-adrenoceptor binding
      parameters determined with [3H]CGP-12177 ((-)-4-(3-t- butylamino-2-hydroxypropxy)
      [5,7-3H]benzimidazol-2-one). However, prolonged administration of all three
      antidepressant drugs induced a downregulation of beta-adrenoceptors. The results
      of the present study confirm the involvement of cortical GABAA rather than GABAB
      receptors in the olfactory bulbectomy animal model of human depression. Moreover,
      the data further support the hypothesis that a decrease in function of the GABAA
      receptor complex could play a role in the therapeutic effects of antidepressant
      treatments.

PMID- 7813566
TI  - Inhibitory effects of quercetin and staurosporine on phasic contractions in rat
      vascular smooth muscle.
AB  - The aim of this work was to analyze the effects of quercetin and staurosporine on
      the phasic contractile responses in rat aorta induced by noradrenaline, 5
      hydroxytryptamine (5-HT, serotonin) and caffeine in Ca(2+)-free media. Both
      quercetin and staurosporine inhibited the contractions induced by 10(-5) M
      noradrenaline, 10(-5) M 5-HT and 20 mM caffeine in Ca(2+)-free solution. Phorbol
      12-myristate 13-acetate (5 x 10(-8) M) enhanced this transient contraction
      elicited by noradrenaline, an effect that was abolished by quercetin (5 x 10(-5)
      M). The relaxant effects of quercetin on 80 mM KCl induced contractions were
      similar in normal and low Na+ solution, e.g. when Ca2+ efflux through the
      Na+/Ca2+ exchanger was inhibited. Furthermore, quercetin or staurosporine had no
      effect on 45Ca2+ efflux under resting conditions or when stimulated by 10(-5) M
      noradrenaline. These results suggested that the inhibitory effects of quercetin
      and staurosporine on phasic contractile responses induced by receptor agonists in
      Ca(2+)-free media do not seem to be related to changes in cellular Ca2+
      regulation but to an inhibitory effect on the regulation of contractile proteins,
      an effect probably related to the decreased sensitivity of contractile elements
      to Ca2+ that apparently resulted from the inhibitory effects of quercetin and
      staurosporine on protein kinases.

PMID- 7813567
TI  - Nizofenone, a neuroprotective drug, suppresses glutamate release and lactate
      accumulation.
AB  - It was investigated whether nizofenone, 2'-chloro-2-(2-diethylaminomethyl-1-
      imidazolyl)-5-nitrobenzophenone fumarate, shows neuroprotective effect by
      inhibiting glutamate release and lactate accumulation in rats. Nizofenone (10
      mg/kg i.p.) significantly inhibited neuronal cell death in the hippocampus CA1
      pyramidal cells 7 days after 15 min of ischemia caused by 4-vessel occlusion. The
      extracellular level of glutamate and lactate increased in the hippocampus during
      ischemia. Upon reperfusion, the glutamate level decreased rapidly but, in
      contrast, the lactate level increased further and reached a maximum at 15 min
      following reperfusion. Nizofenone (10 mg/kg i.p.) completely inhibited the
      ischemic glutamate increase and post-ischemic lactate increase. These results
      suggest that the inhibition of ischemic release of glutamate and post-ischemic
      accumulation of lactate could contribute greatly to the neuroprotective effect of
      nizofenone.

PMID- 7813568
TI  - Intrathecal neuromedin C enhances mechanical nociception: possible involvement of
      NMDA receptors.
AB  - Intrathecal administration of neuromedin C (3, 10 nmol/rat) significantly
      decreased the nociceptive threshold of rats in the paw-pressure test. This effect
      was abolished by co-administration of [Leu13 psi(CH2NH)-Leu14]bombesin (10
      nmol/rat), a bombesin receptor antagonist. Co-administration of 2-amino-5
      phosphonovaleric acid (APV) at a dose (10 nmol/rat) which did not affect the
      nociceptive threshold by itself significantly inhibited the effect of neuromedin
      C. 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX) (10 nmol/rat) did not
      significantly inhibit the neuromedin C-induced hyperalgesia. These results
      indicate that neuromedin C could modulate mechanical nociception through bombesin
      receptors at the spinal level, where glutamate is involved through NMDA
      receptors.

PMID- 7813569
TI  - Combined antagonism of adrenoceptors and dopamine and 5-HT receptors underlies
      the atypical profile of clozapine.
AB  - Previous studies have shown that alpha 1-adrenoceptors, dopamine D1-like and 5
      HT2A receptors play an important role in the effects of the atypical neuroleptic,
      clozapine, on the parameter modelling antipsychotic efficacy in the paw test.
      Therefore, it became of interest to investigate whether antagonism of all these
      receptors together would give rise to effects characteristic of clozapine. The
      effects of the combined administration of the alpha 1-adrenoceptor antagonist
      phenoxybenzamine, the dopamine D1 receptor antagonist, SCH 39166 (4-(4-chloro-3
      methoxyphenyl)-1,2- dihydronaphthalene), and the 5-HT2A receptor antagonist,
      ketanserin, were therefore measured in the paw test. The present data show that
      all three drugs together, but not simply combinations of two out of three,
      produced a profile similar to that of clozapine: a significant increase in the
      parameter modelling antipsychotic efficacy and no change in the parameter
      modelling extrapyramidal side-effects.

PMID- 7813570
TI  - Effects of adrenoceptor antagonists on the hyperthermia and hyperglycemia induced
      by prostaglandin F2 alpha in rats.
AB  - We investigated the effects of intraperitoneal administration of adrenoceptor
      antagonists to the hyperthermia and hyperglycemia induced by prostaglandin F2
      alpha (50 micrograms) injected into the third cerebral ventricle in anesthetized
      rats. Phentolamine inhibited the hyperthermia and hyperglycemia induced by
      prostaglandin F2 alpha. Prazosin inhibited the hyperthermia induced by
      prostaglandin F2 alpha, while enhancing the hyperglycemia. Yohimbine inhibited
      the prostaglandin F2 alpha-induced hyperglycemia without an effect on the
      hyperthermia. Propranolol had no effect on either prostaglandin F2 alpha-induced
      hyperglycemia or hyperthermia. These observations suggest that the hyperglycemia
      induced by prostaglandin F2 alpha is regulated by alpha 2-adrenoceptor systems
      while the hyperthermia is regulated by alpha 1-adrenoceptor systems in rats.

PMID- 7813571
TI  - Nitric oxide donors preferentially inhibit neuronally mediated rat gastric acid
      secretion.
AB  - Continuous i.v. infusion of the nitric oxide (NO) donors, S-nitroso-glutathione
      (10-50 micrograms kg-1 min-1) and S-nitroso-N-acetyl-penicillamine (10 micrograms
      kg-1 min-1) inhibited neuronally mediated gastric acid secretion, as induced by
      gastric distension (20 cm water) or i.v. bolus administration of 2-deoxy-D
      glucose (150 mg kg-1) in the anaesthetized rat. By contrast, gastric acid
      responses to i.v. infusion of submaximal doses of pentagastrin (8 micrograms kg-1
      h-1) or histamine (1 mg kg-1 h-1) were not influenced by these NO donors. These
      findings suggest that NO does not directly influence acid secretion in vivo but
      could play an inhibitory modulator role in neuronally mediated acid responses.

PMID- 7813572
TI  - Effects of nifedipine on phasic and tonic vasoconstrictor responses to Sgd 101/75
      in the isolated perfused rabbit ear artery.
AB  - The relative importance of extracellular Ca2+ influx and intracellular Ca2+
      release for the vasoconstrictor response to Sgd 101/75 (4(2-imidazoline-amino)-2
      methyl-indazol-chlorhydrate), an alpha 1-adrenoceptor agonist, was examined in
      perfused rabbit ear arteries. Sdg 101/75 induced a phasic and a tonic
      vasoconstrictor response in a concentration-dependent manner. It is a full
      agonist on the tonic response but a partial agonist on the phasic response.
      Nifedipine preferentially inhibited the tonic but not the phasic response to Sgd
      101/75. Therefore, Sgd 101/75 appears to require both the intracellular Ca2+
      release and extracellular Ca2+ influx for its phasic and tonic responses in
      rabbit ear arteries, respectively.

PMID- 7813573
TI  - Gamma-guanidinobaclofen is a peripheral GABAB receptor agonist.
AB  - In the guinea-pig isolated ileum, both baclofen and gamma-guanidinobaclofen
      elicited dose-dependent depression of cholinergic twitch contractions, sensitive
      to the GABAB receptor antagonists phaclofen and 2-hydroxysaclofen. gamma
      Guanidinobaclofen was 5 times less potent than R,S-(+/-)-baclofen in depressing
      the contractions. The corresponding GABA analogs, guanidinoacetic acid, beta
      guanidinopropionic acid and gamma-guanidinobutanoic acid were inactive. In rat
      neocortical slices maintained in Mg(2+)-free medium, baclofen (1-50 microM)
      reduced the amplitude and rate, whilst gamma-guanidinobaclofen (1 mM) has a very
      weak GABAB receptor agonist action, 100 times weaker than baclofen. gamma
      Guanidinobaclofen is therefore a GABAB receptor agonist, more potent at
      peripheral than central GABAB receptors.

PMID- 7813574
TI  - Memantine-induced dopamine release in the prefrontal cortex and striatum of the
      rat--a pharmacokinetic microdialysis study.
AB  - Memantine (1-amino-3,5-dimethyl-adamantane) has therapeutic potential in
      Parkinson's disease and dementia. However, its effect on dopaminergic activity in
      the central nervous system is still unclear. Therefore, we studied the effect of
      memantine on dopamine release in prefrontal cortex and striatum, using in vivo
      microdialysis. Memantine (5, 10 and 20 mg/kg i.p.) caused a dose-dependent
      increase in dopamine release up to nearly 50% over basal levels. The output of
      the metabolites was of later onset and longer duration in prefrontal cortex and
      in striatum. After administration of 10 and 20 mg/kg, in both brain areas
      memantine levels could be detected over the investigated period of 160 min. The
      maximal concentrations (Cmax) differed dose dependently, whereas the time to
      reach this maximum (tmax) was almost identical (68.5 +/- 3.4 min). From the flat
      elimination profile a half-life of 2.8 +/- 0.5 h (range 2-3.4 h) was calculated.
      These data demonstrate enhanced dopamine release and metabolism after memantine
      treatment and support the assumption of an interaction between noncompetitive
      NMDA-receptor antagonists and dopaminergic systems.

PMID- 7813575
TI  - Thrombolytic efficacy of a modified tissue-type plasminogen activator, SUN9216,
      in the rat middle cerebral artery thrombosis model.
AB  - We have developed a model whereby the middle cerebral artery in an experimental
      animal can be occluded by a photochemical reaction between rose bengal and green
      light. This causes endothelial injury followed by platelet adhesion, aggregation
      and formation of a platelet-rich thrombus at the site of the photochemical
      reaction. SUN9216, a modified tissue-type plasminogen activator, is a new
      thrombolytic agent which consists of the fibrin kringle 1 domain of plasminogen
      and the two kringles, the serine protease domains of the native tissue-type
      plasminogen activator. The mannose glycosylation site on the kringle 1 of tissue
      type plasminogen activator is modified to yield a compound with a longer half
      life in the blood than native tissue-type plasminogen activator. We evaluated the
      thrombolytic effects of recombinant tissue-type plasminogen activator and SUN9216
      in the thrombotically occluded rat middle cerebral artery. SUN9216 was
      administered by continuous infusion or as a single bolus injection 30 min after
      the middle cerebral artery had been occluded by a thrombus. Both SUN9216 and
      recombinant tissue-type plasminogen activator caused reopening of the middle
      cerebral artery by thrombolysis. The efficacy of SUN9216 was higher than that of
      recombinant tissue-type plasminogen activator. Further, the area of ischaemic
      cerebral damage caused by the middle cerebral artery occlusion was significantly
      (P < 0.05) reduced by SUN9216, but in this respect, recombinant tissue-type
      plasminogen activator was ineffective.

PMID- 7813576
TI  - Delta-opioid receptor agonists inhibit neuromuscular transmission in human colon.
AB  - The present study was undertaken to investigate the possible role of delta-opioid
      receptors in the neuroregulation of human colonic motility by using a superfusion
      model. Spontaneous mechanical activity and responses to electrical transmural
      nerve stimulation of both longitudinal and circular muscle strips from the human
      sigmoid colon were studied. Exogenously added delta-opioid receptor agonists did
      not modify spontaneous contractile activities of either type of strip. Nerve
      stimulation induced a triphasic response composed of an initial contraction
      followed by a relaxation and an off-contraction. This response was mediated by
      cholinergic excitatory nerves and non-adrenergic, non-cholinergic excitatory and
      inhibitory nerves. [Met5]Enkephalin and the synthetic delta-opioid receptor
      agonist [D-Pen2,D-Pen5]enkephalin (DPDPE) significantly decreased the amplitude
      of the initial contraction and of the off-contraction. The effects of both delta
      opioid receptor agonists were reduced in the presence of either the delta-opioid
      receptor antagonist, ICI 174864, or another delta-opioid receptor antagonist,
      naltrindole. ICI 174864 prevented neither the effects of a natural kappa-opioid
      receptor agonist, dynorphin-(1-13) nor those of the mu-opioid receptor agonist,
      PL017. Therefore, these data suggest that delta-opioid receptors might be
      involved in the neuroregulation of smooth muscle of human colon and may mediate
      inhibition of cholinergic and non-cholinergic excitatory transmission within the
      myenteric plexus.

PMID- 7813577
TI  - Imidazolines stimulate release of insulin from RIN-5AH cells independently from
      imidazoline I1 and I2 receptors.
AB  - The effect on insulin release of efaroxan, an alpha 2-adrenoceptor antagonist and
      a highly potent drug at imidazoline I1 receptors, and the effects of seven other
      imidazoline compounds selective for the imidazoline I1 or I2 receptors, were
      studied in the rat insulinoma cell line RIN-5AH. The cells released insulin in
      response to glucose (0.3-10 mM), and efaroxan (100 microM) potentiated glucose
      induced insulin release. (-)-Adrenaline completely displaced the binding of
      [125I]p-iodoclonidine to membranes of RIN-5AH cells, indicating that these cells
      do not express imidazoline I1 receptors. Cirazoline and idazoxan (100 microM),
      both highly potent drugs at imidazoline I2 receptors, and the guanidines guanoxan
      and amiloride (200 microM), also promoted insulin release from RIN-5AH cells.
      Irreversible blockade of imidazoline I2 receptors with 10 microM clorgyline did
      not prevent the stimulatory effects of cirazoline or idazoxan; however, these
      compounds completely reversed the inhibition by diazoxide (250 microM), an opener
      of ATP-dependent K+ channels (K+ATP channels), of glucose-induced insulin
      release. These data indicate that the imidazoline/guanidine compounds promote
      insulin release from RIN-5AH cells, by interacting with a novel binding site
      related to K+ATP channels that does not represent any of the known imidazoline I1
      or I2 receptors.

PMID- 7813578
TI  - Clozapine injected into the nucleus accumbens potentiates apomorphine-induced jaw
      movements.
AB  - The effects of clozapine injected into the nucleus accumbens on apomorphine
      induced jaw movements were studied. Jaw movements induced by apomorphine (0.5
      mg/kg i.v.) were potentiated by clozapine (10 micrograms/0.2 microliters)
      injected into the nucleus accumbens 10 min before apomorphine. Enhancement of the
      apomorphine-induced jaw movements was also found with the muscarinic
      acetylcholine receptor antagonist, methylscopolamine (2.5 micrograms), whereas
      the acetylcholine receptor agonist, carbachol (2.5 micrograms), inhibited the
      effects of apomorphine. Injection of a smaller dose of carbachol (0.1 microgram)
      alone into the nucleus accumbens 10 min before failed to alter the effects of
      apomorphine but prevented the potentiation induced by clozapine. Both the 5
      hydroxytryptamine(5-HT)2A receptor antagonist, 2-(2-dimethylaminoethylthio)-3
      phenylquinoline hydrochloride (ICI 169,369, 0.1 and 0.2 microgram), and the alpha
      1-adrenoceptor antagonist, prazosin (0.05 and 0.2 microgram), failed to affect
      the effects of apomorphine(0.5 mg/kg i.v.). In contrast, clozapine (1, 5 and 10
      micrograms), ICI 169,369 (0.1 and 0.2 microgram) or prazosin (0.05 and 0.2
      microgram) given into the ventral striatum inhibited the effects of apomorphine
      (0.5 mg/kg i.v.). It is suggested that the clozapine-induced potentiation in the
      nucleus accumbens might be due to its antimuscarinic properties.

PMID- 7813579
TI  - Vasodilator effect of carboxy-2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl in
      the coronary circulation: in vivo and in vitro studies.
AB  - 2-Phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO) derivatives, new
      radical forms of nitric oxide (NO) antagonists, are reported to react with NO and
      generate NO2 and 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl (PTI)
      derivatives. We found that carboxy-PTI, a water-soluble derivative of PTI, showed
      a potent vasodilator effect in the canine coronary artery system. In anesthetized
      dogs, intracoronary infusion of carboxy-PTI significantly increased the coronary
      flow in a dose-dependent manner without altering systemic hemodynamic variables.
      This coronary flow increasing effect of carboxy-PTI was not influenced by
      pretreatment with either NG-nitro-L-arginine methyl ester or 8-phenyltheophylline
      or autonomic blockade. However, the flow increasing effect of carboxy-PTI was
      abolished by reducing carboxy-PTI with ascorbic acid to a non-radical form of
      carboxy-PTI, indicating that carboxy-PTI shows its effect only in a radical form.
      In isolated canine coronary arterial rings, carboxy-PTI caused endothelium
      independent relaxation. This relaxation response was significantly attenuated by
      pretreatment with methylene blue, an inhibitor of soluble guanylate cyclase.
      Thus, carboxy-PTI has an endothelium-independent coronary vasodilator effect in
      both large conduit arteries and small resistance vessels. The results of the in
      vitro experiment suggested that the activation of soluble guanylate cyclase of
      the vascular smooth muscle cell may be involved, at least in part, in the
      vasodilator mechanism of carboxy-PTI in large conduit arteries.

PMID- 7813580
TI  - Caffeine cross-tolerance to selective dopamine D1 and D2 receptor agonists but
      not to their synergistic interaction.
AB  - This study examined the role of dopamine systems in tolerance to caffeine-induced
      stimulation of motor activity in the rat. Selective dopamine D1 and D2 receptor
      agonists were tested alone and combined in rats receiving caffeine chronically by
      a method of scheduled access to a caffeine solution or in control rats receiving
      no caffeine. Rats treated chronically with oral caffeine were tolerant to the
      motor stimulant effects of caffeine (3.0-100 mg/kg, i.p.). The partial dopamine
      D1 receptor agonist SKF-77434 (1.0-30 mg/kg, s.c.) and the dopamine D2 receptor
      agonists quinpirole (0.03-10 mg/kg, s.c.) and R(-)-pro-pylnorapomorphine (NPA,
      0.03-1.0 mg/kg, s.c.) dose-dependently increased activity in control rats.
      Caffeine-treated rats were cross-tolerant to the locomotor stimulant effect of
      these selective dopamine D1 and D2 receptor agonist. The concurrent
      administration of the partial dopamine D1 receptor agonist SKF-38393 (10 mg/kg,
      s.c.) with the dopamine D2 receptor agonists quinpirole and R(-)
      propylnorapomorphine had a synergistic effect on locomotor activity in both
      control and caffeine-treated rats. This synergistic effect was also seen when the
      partial dopamine D1 receptor agonist SKF-77434 (1.0 and 10 mg/kg, s.c.) was given
      in combination with quinpirole. There was little or no cross-tolerance to the
      concurrent administration of selective dopamine D1 and D2 receptor agonists. It
      appears that tolerance to the locomotor stimulant effect of caffeine is mediated
      by both dopamine D1 and D2 receptor sub-types. Cross-tolerance occurs to drugs
      that activate a single type of dopamine receptor but not to drug combinations
      that concurrently activate more than one type of receptor.

PMID- 7813581
TI  - 5-HT1A and muscarinic acetylcholine receptors jointly regulate passive avoidance
      behavior.
AB  - The present study was designed to investigate the effects of combined stimulation
      of 5-HT1A or 5-HT2 receptors and blockade of muscarinic acetylcholine receptors
      on passive avoidance behavior. Administration of 8-hydroxy-2-(di-n
      propylamino)tetralin (8-OH-DPAT), a 5-HT1A receptor agonist, and 1-(2,5-dimethoxy
      4-iodophenyl)-2-aminopropane (DOI), a 5-HT2 receptor agonist, impaired passive
      avoidance acquisition (pre-training injections) and consolidation (post-training
      injections) performance. Ketanserin, a 5-HT2 receptor antagonist, blocked the
      performance-impairing effect of DOI on passive avoidance consolidation.
      Interestingly, 5-HT receptor agonists may affect passive avoidance consolidation
      only during the immediate post-training period, as passive avoidance testing
      performance was not modulated by 8-OH-DPAT or DOI injected 30 min after the
      training trial. Furthermore, passive avoidance retention (pre-testing injections)
      performance was impaired only by the highest dose of 8-OH-DPAT, and DOI had no
      effect on passive avoidance retention. Next, the effects of combined 5-HT and
      acetylcholine receptor manipulations on passive avoidance behavior were studied.
      The effects on passive avoidance behavior of a combination of subthreshold doses
      of scopolamine, a muscarinic acetylcholine receptor antagonist, and 8-OH-DPAT
      were compared to those of a single high dose of scopolamine. A combination of
      small doses of scopolamine and 8-OH-DPAT impaired acquisition and consolidation
      of passive avoidance performance, but a single high dose of scopolamine impaired
      only acquisition performance. The small dose of 8-OH-DPAT also aggravated medial
      septal lesion-induced passive avoidance acquisition and consolidation failure.
      The combination of small doses of scopolamine and DOI had no effect on passive
      avoidance behavior. Peripherally acting scopolamine methylbromide alone or in
      combination with 8-OH-DPAT had no effect on passive avoidance performance. Motor
      activity in a swimming pool was altered by single and combined drug treatments;
      high doses of 8-OH-DPAT and scopolamine, and the combination of small doses of 8
      OH-DPAT + scopolamine increased speed of swimming. Medial septum-lesioning also
      increased speed of swimming but the speed was not increased further by 8-OH-DPAT.
      The present data suggest that behavioral defect caused by hypostimulation of
      muscarinic acetylcholine receptors is aggravated by concurrent 5-HT1A receptor
      stimulation.

PMID- 7813582
TI  - Stimulant effects of 5-hydroxytryptamine on guinea pig stomach preparations in
      vitro.
AB  - 5-Hydroxytryptamine (5-HT) contracts and relaxes isolated stomach preparations.
      This study attempts to characterise receptors involved in the contractile
      response using electrically stimulated circular muscle strips from guinea pig
      stomach. Electrically induced contractions were abolished by atropine and
      tetrodotoxin. 5-HT enhanced contractions in corpus and fundus strips with pEC50%
      values (-log10 of the concentrations causing a 50% increase in twitch height) of
      9.6 and 9.1, respectively. 5-Carboxamidotryptamine and 8-OH-DPAT (8-hydroxy-2-(di
      n-propylamino)tetralin), 5-HT1A receptor agonists, and alpha-methyl-5-HT, an
      agonist at 5-HT2 receptors, reduced contractions. The 5-HT3 receptor agonist, 2
      methyl-5-HT, increased contractions. The effect of 2-methyl-5-HT but not of 5-HT
      was antagonized by the 5-HT3 receptor antagonist, tropisetron (10(-7) M). The 5
      HT3 receptor antagonists, tropisetron, MDL 72222 (1 alpha H,3 alpha,5 alpha H
      tropan-3-yl-3,5-dichlorobenzoate), grainsetron and ondansetron, did not modify
      twitch responses at concentrations below 10(-7) M. Renzapride and metoclopramide,
      agonists at 5-HT4 receptors, increased contractions and this effect was inhibited
      by the 5-HT4 receptor antagonist SDZ 205-557 (2-methoxy-4-amino-5-chloro-benzoic
      acid 2-(diethylamino) ethyl ester) with a pA2 of 7.4. The effect of 5-HT at a
      submaximal concentration of 10(-8) M was blocked by SDZ 205-557 (10(-6) M). It is
      concluded that electrically induced contractions in guinea pig stomach strips are
      enhanced by activation of 5-HT3- and 5-HT4 receptors and are diminished by 5-HT1
      receptor agonists.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7813583
TI  - Direct excitatory opiate effects mediated by non-synaptic actions on rat medial
      vestibular neurons.
AB  - Opiates increase firing of rat medial vestibular nucleus neurons. We have
      attempted to determine the mechanism of these excitatory opiate actions by
      extracellular recording of neuronal activity with ionophoretic application of
      opiate agonists and bath application of antagonists. The spontaneous activity of
      approximately 30% of medial vestibular neurons, scattered throughout the nucleus,
      was increased by ionophoretic application of either morphine or [D-Ala2]leucine
      enkephalin, implicating the presence of both mu and delta opiate receptors. The
      responses to both were blocked by the opiate receptor antagonist, naloxone. In
      only a few neurons opiates decreased firing. Most previous reports of direct
      opiate excitation have proven to be due to disinhibition. This is not the case
      here, as indicated by three observations: 1) the excitatory opiate response was
      sustained when gamma-aminobutyric acid (GABA) receptors were blocked by
      bicuculline; 2) perfusion of a solution containing 0.1 mM Ca2+ and 6.3 mM Mg2+
      blocks synaptic transmission, but does not block the excitatory responses to both
      opiates and 3) the opiate-induced depolarization and action potential generation
      was evident in neurons whose spontaneous firing was almost totally depressed by
      adenosine. These results indicate that the excitation is neither due to
      disinhibition nor to a presynaptic opiate action. We conclude that medial
      vestibular neurons have postsynaptic opiate receptors that mediate direct
      neuronal excitation.

PMID- 7813584
TI  - BW1003C87 and NBQX but not CGS19755 reduce glutamate release and cerebral
      ischemic necrosis.
AB  - This study examines the relationship between the concentration of extracellular
      glutamate released during 30 min of forebrain ischemia, and the subsequent
      development of ischemic neural necrosis, in the presence of three agents which
      act at distinct sites on the glutamatergic synapse: a presynaptic inhibitor of
      glutamate release (5-(2,3,5-trichlorophenyl)-2,4-diamino-pyramidine ethane
      sulphonate (BW1003C87)); a competitive NMDA receptor antagonist (cis-4
      phosphonomethyl-2-piperidine carboxylic acid (CGS19755)); and a competitive AMPA
      receptor antagonist (2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline
      (NBQX)). Pretreatment with either BW1003C87 or NBQX markedly attenuated the peak
      concentration of extracellular glutamate and offered protection from post
      ischemic neuronal necrosis in the CA1 hippocampus. In contrast, pretreatment with
      CGS19755 had no effect on extracellular glutamate release and did not protect CA1
      hippocampal neurons from ischemic injury.

PMID- 7813585
TI  - Are the cardiovascular effects and '5-HT syndrome' induced by MDL 73,975 and
      flesinoxan in the dog mediated by 5-HT1A receptors?
AB  - The cardiovascular effects of the 5-HT1A receptor agonists MDL 73,975 (8-[2-(2,3
      dihydro-8-methoxy-1,4-benzodoxin-2-yl)methylaminol++ +]-ethyl]-8-
      azaspiro[4,5]decane-7,9-dione hydrochloride) and flesinoxan (10-300 micrograms/kg
      subcutaneously, s.c.), the 5-HT1A receptor antagonist NAN 190 (2-[4-[4-(2
      methoxyphenyl)-1-piperazinyl]butyl]-1H-isoindole-1,3(2H)- dione,1,2
      ethanedioate), and the alpha 1-adrenoceptor antagonist prazosin have been
      investigated in conscious normotensive and renal hypertensive dogs. In
      normotensive dogs the increases in heart rate and respiratory rate induced by
      both agonists were dose-related, as were the decreases in systolic and diastolic
      blood pressure induced by MDL 73,975. Both compounds caused a dose-related
      increase in the intensity of the '5-HT syndrome'. After pretreatment with NAN 190
      (100 micrograms/kg s.c.) the increases in heart rate, respiratory rate and
      symptoms of the '5-HT syndrome' were significantly reduced but the decreases in
      systolic and diastolic pressure were additive. Pretreatment with prazosin (100
      micrograms/kg s.c.) antagonized the '5-HT syndrome' and the increase in
      respiratory rate. Similar responses were evident in renal hypertensive dogs.
      Tolerance did not develop to the increases in heart rate, respiratory rate and
      manifestations of the '5-HT syndrome' in normotensive dogs during 5 days of
      treatment with MDL 73,975 or flesinoxan. In conclusion, MDL 73,975 and flesinoxan
      induced a 5-HT1A receptor-mediated fall in blood pressure but the changes in
      heart rate, respiratory rate and the '5-HT syndrome' are probably mediated by
      alpha 1-adrenoceptors.

PMID- 7813586
TI  - Effects of Trolox C and SIN-1 on arachidonic acid metabolism and on cyclic GMP
      formation in leukocytes.
AB  - The effects of Trolox C (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid),
      a vitamin E analogue, (60-900 microM) and SIN-1 (3-morpholino sydnonimine), a
      nitric oxide donor, (30-3000 microM) on arachidonic acid metabolism and on cyclic
      GMP formation in calcium ionophore A23187 (calcimycin)-stimulated human
      polymorphonuclear leukocytes were investigated. Trolox C elicited a dose
      dependent decrease in leukotriene B4 levels and increase in prostaglandin E2
      levels but did not affect cyclic GMP levels. SIN-1 dose dependently inhibited
      leukotriene B4 and stimulated prostaglandin E2 and cyclic GMP formation.
      Dibutyryl cyclic GMP did not affect the formation of leukotriene B4 and
      prostaglandin E2. Trolox C (180 microM), which itself had no effect on cyclic GMP
      levels, enhanced the effect of SIN-1 (100 microM) on cyclic GMP levels more than
      5-fold. The effects of SIN-1 on arachidonic acid metabolism seem to be
      independent of cyclic GMP and are probably due to nitric oxide. In this
      experimental model both Trolox C and SIN-1 have similar actions on the
      prostaglandin/leukotriene ratio, and Trolox C potentiates the SIN-1-induced
      increase in cyclic GMP levels.

PMID- 7813587
TI  - Role of nitric oxide/cyclic GMP in i.c.v. administered beta-endorphin- and (+)
      cis-dioxolane-induced antinociception in the mouse.
AB  - (+)-cis-Dioxolane (0.5-2 micrograms), a muscarinic receptor agonist, given
      intracerebroventricularly (i.c.v.) produced a dose-dependent inhibition of the
      tail-flick response in male ICR mice. (+)-cis-Dioxolane given i.c.v. at a
      subanalgesic dose (0.25 micrograms), selectively potentiated the antinociceptive
      response induced by i.c.v. administered beta-endorphin, an epsilon-opioid
      receptor agonist, but not morphine or [D-Ala2,NMePhe4,Gly5-ol]enkephalin (DAMGO),
      mu-opioid receptor agonists, [D-Pen2,D-Pen5]enkephalin (DPDPE), a delta receptor
      agonist, or trans(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-
      benzeneacetamide methane sulfonate (U50,488H), a kappa-opioid receptor agonist.
      The antinociceptive response induced by (+)-cis-dioxolane given i.c.v. was
      attenuated by i.c.v. treatment with N omega-nitro-L-arginine (1 microgram),
      hemoglobin (120 micrograms) or methylene blue (10 micrograms). The
      antinociception induced by carbachol given i.c.v. was also antagonized by the
      i.c.v. treatment with N omega-nitro-L-arginine (1 microgram). However, the same
      treatment with N omega-nitro-L-arginine, hemoglobin or methylene blue did not
      affect the beta-endorphin-induced antinociception. The potentiation of beta
      endorphin-induced antinociception by (+)-cis-dioxolane was reversed by i.c.v.
      treatment with N omega-nitro-L-arginine (1 microgram), hemoglobin (120
      micrograms) or methylene blue (10 micrograms). On the other hand, the
      antinociceptive response induced by (+)-cis-dioxolane (1 microgram) given i.c.v.
      was potentiated by i.c.v. administered L-arginine (20 micrograms) but not D
      arginine (20 micrograms). Dibutyryl cyclic GMP at 0.5-2.0 micrograms given i.c.v.
      produced an antinociceptive response and at subanalgesic dose (0.1 microgram)
      potentiated i.c.v. beta-endorphin-induced antinociception.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7813588
TI  - Pharmacological properties of ureido-acetamides, new potent and selective non
      peptide CCKB/gastrin receptor antagonists.
AB  - We present here the pharmacological properties of 3 ureido-acetamide members of a
      novel family of non-peptide cholecystokinin-B (CCKB) receptor antagonists. RP
      69758 (3-(3-[N-(N-methyl N-phenyl-carbamoylmethyl) N-phenyl-carbamoylmethyl]
      ureido)phenylacetic acid), RP 71483 ((E)-2-[3-(3-hydroxyiminomethyl phenyl)
      ureido] N-(8-quinolyl) N-[(1,2,3,4-tetrahydro 1
      quinolyl)carbonylmethyl]acetamide) and RP 72540 ((RS)-2-[3-(3-[N-(3-methoxy
      phenyl) N-(N-methyl N-phenyl-carbamoylmethyl) carbamoylmethyl] ureido) phenyl]
      propionic acid) displayed nanomolar affinity for guinea-pig, rat and mouse CCKB
      receptors labelled with [3H]pCCK-8 or with the selective CCKB receptor ligand
      [3H]pBC264. RP 69758 and RP 72540 showed selectivity factors in express of 200
      for CCKB versus CCKA receptors. All three compounds had also high affinity for
      gastrin binding sites in the stomach. The ureido-acetamides behaved as potent
      antagonists of CCK-8-induced neuronal firing in rat hippocampal slices in vitro,
      a functional model of brain CCKB receptor mediated responses. RP 69758 is also a
      potent gastrin receptor antagonist in vivo that dose dependently inhibits gastric
      acid secretion induced by i.v. injection of pentagastrin in the rat. None of the
      three ureido-acetamides, at concentrations up to 1 microM, significantly blocked
      CCK-8-evoked contractions of the guinea-pig ileum in vitro, a CCKA receptor
      bioassay. In ex vivo binding studies, i.p. administration of RP 69758 and RP
      72540 resulted in a dose-dependent inhibition of [3H]pCCK-8 binding in mouse
      brain homogenate. However, the relative penetration of these ureido-acetamides
      into the forebrain after peripheral administration was below 0.01%. RP 71483 did
      not appear to cross the blood-brain barrier in quantities sufficient to prevent
      [3H]pCCK-8 binding at low doses, a property that makes it suitable for the
      exploration of the peripheral versus central origin of the behavioural effects
      observed following systemic administration of CCK. RP 69758, RP 71483 and RP
      72540 are highly potent and selective non-peptide CCKB receptor antagonists which
      are useful tools to explore the physiological functions of CCKB receptors.

PMID- 7813589
TI  - Endothelium-dependent, nitric oxide-mediated inhibition of angiotensin II-induced
      contractions in rabbit aorta.
AB  - The role of endothelium in angiotensin II-induced contractions of the rabbit
      aorta and the mechanism involved were investigated. Destruction of the
      endothelium significantly shifted the concentration-response curve for
      angiotensin II to the left in a non-parallel manner and enhanced the maximal
      response. The EC50 and Emax values obtained from the rings with and without
      functional endothelium were 2.44 +/- 0.13 x 10(-9) M, 4.50 +/- 0.45 g and 1.21 +/
      0.14 x 10(-9) M (n = 8, P < 0.05), 5.73 +/- 0.55 g (n = 8, P < 0.05),
      respectively. Indomethacin (10(-5) M) did not significantly alter the
      concentration-dependent response to angiotensin II in the presence of
      endothelium. Three inhibitors of nitric oxide synthase (NG-monomethyl-L-arginine;
      NG-nitro-L-arginine, and NG-nitro-L-arginine methyl ester) at 10(-4) M caused a
      similar endothelium-dependent potentiation of angiotensin II-induced contractions
      in the aortic rings with, but not in those without endothelium. These effects
      were reversed by L-arginine (3 x 10(-3) M) but not by D-arginine (3 x 10(-3) M).
      Angiotensin II in a concentration range of 10(-16) to 10(-6) M did not relax the
      endothelium-intact rings precontracted with phenylephrine (2 x 10(-7) M). In the
      presence of endothelium, the angiotensin II subtype 2 receptor antagonist, 1-[(4
      amino-3-methylphenyl]-5-(diphenylacetyl)-4,5,6,7-tetrahydro- 1H- imidazol[4,5
      C]pyridine-6-carboxylic acid (PD 123177), caused neither relaxation of the rings
      precontracted with phenylephrine nor alteration of the concentration-response
      curve for angiotensin II.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7813590
TI  - Endothelin ETB receptor antagonist, RES-701-1: effects on isolated blood vessels
      and small intestine.
AB  - RES-701-1 (cyclic (Gly1-Asp9)(Gly-Asn-Trp-His-Gly-Thr-Ala-Pro-Asp-Trp-Phe- Phe
      Asn-Tyr-Tyr-Trp)), a peptide isolated from Streptomyces sp., has been reported to
      inhibit the endothelin ETB receptor. We examined the effects of this peptide on
      the blood vessels and the small intestine. In isolated rat aorta without
      endothelium, 10 microM RES-701-1 did not affect the resting tone, nor did it
      attenuate the contractions induced by endothelin-1, endothelin-3 or
      norepinephrine. In the aorta with endothelium, 3 microM RES-701-1 shifted the
      concentration-response curves for the contractile effects of endothelin-1 and
      endothelin-3 to the left. Removal of endothelium showed a similar effect to 3
      microM RES-701-1. In the norepinephrine-stimulated aorta, endothelium-dependent
      relaxation induced by endothelin-3 was antagonized by 0.3-10 microM RES-701-1 in
      a concentration-dependent manner. In the guinea pig ileum stimulated by
      carbachol, endothelin-3 induced a transient relaxation followed by sustained
      relaxation. RES-101-1 (3 microM) selectively inhibited the transient relaxation.
      Since it has been shown that the contractile effects of endothelins in the aorta
      are mediated by the endothelin ETA receptor whereas the endothelium-dependent
      relaxation and the ileal relaxation are mediated by the endothelin ETB receptor,
      it is suggested that RES-701-1 is a selective antagonist against the endothelin
      ETB receptor.

PMID- 7813591
TI  - Fibroblast growth-promoting activity in proliferative vitreoretinopathy:
      antagonism by acetylsalicylic acid.
AB  - Proliferative vitreoretinopathy is a severe reactive process which leads to the
      formation of cellular membranes on the surface of the retina and in the vitreous.
      We determined the fibroblast growth-promoting activity of intraocular fluid from
      patients suffering from proliferative vitreoretinopathy, retinal detachment or
      cataract and further evaluated the effect of acetylsalicylic acid on growth
      stimulated fibroblasts. The results demonstrated a significant enhancement of
      growth-promoting activity of intraocular fluid in proliferative vitreoretinopathy
      as compared to that of control samples. We showed that the augmented growth
      promoting activity of intraocular fluid in proliferative vitreoretinopathy was
      significantly antagonized by inhibition of cyclooxygenase with acetylsalicylic
      acid (ID50 approximately 5 microM). In contrast, no significant effect was seen
      in corresponding control experiments. The findings suggest that metabolites of
      the cyclooxygenase pathway are involved in the regulation of enhanced intraocular
      fluid-induced fibroblast proliferation in proliferative vitreoretinopathy and
      that acetylsalicylic acid might be useful as an antiproliferative agent in
      intraocular fibrogenesis.

PMID- 7813592
TI  - Evidence for an antagonistic angiotensin II/alpha 2-adrenoceptor interaction in
      the nucleus tractus solitarii.
AB  - Interactions between alpha 2-adrenoceptors and angiotensin II receptors were
      evaluated in the nucleus tractus solitarii of the rat by means of quantitative
      receptor autoradiography and cardiovascular analysis. In binding experiments
      using l-noradrenaline to compete for [3H]p-aminoclonidine binding sites,
      angiotensin II (1 nM) increased the IC50 value of l-noradrenaline by 50%. The
      angiotensin AT1 receptor antagonist, DUP753 (losartan), not only blocked this
      action but also decreased the IC50 value of l-noradrenaline. The modulatory
      effect of angiotensin II was also evaluated after addition of both DUP753 and
      PD123319, an angiotensin AT2 receptor antagonist, and counteraction of the
      reduction in the IC50 value of l-noradrenaline was observed. In saturation
      experiments angiotensin II increased the KD and Bmax values of [3H]p
      aminoclonidine binding sites, compatible with possible uncoupling of the alpha 2
      adrenoceptors. Cardiovascular analysis demonstrated that a threshold dose of
      angiotensin II (0.05 pmol) counteracted the vasodepressor effect produced by an
      ED50 dose of l-adrenaline, l-noradrenaline or clonidine coinjected in the nucleus
      tractus solitarii. DUP753 fully blocked this in vivo modulation of alpha 2
      adrenoceptors by angiotensin II. These findings suggest the existence of an
      antagonistic angiotensin AT1/alpha 2-adrenoceptor interaction in the nucleus
      tractus solitarii. Therefore, it can be surmised that the activation of
      angiotensin II AT1 receptors may reduce the transduction of the alpha 2
      adrenoceptors and thus the alpha 2-mediated vasodepressor responses.

PMID- 7813593
TI  - Identification of beta-adrenoceptors in rat lymph nodes and spleen: an
      autoradiographic study.
AB  - The anatomical localization of beta 1 and beta 2-adrenoceptors was studied in rat
      lymphoid tissues by quantitative autoradiography using [125I]cyanopindolol as a
      ligand. In lymph nodes, a significant density of these receptors was found in the
      medullary cords and the interfollicular cortex, while only low densities were
      observed in the paracortex. No detectable binding appeared in the remaining
      areas. In the spleen, these receptors were mainly localized in the capsule,
      marginal zone of white pulp and red pulp, while the labelling over the white pulp
      was extremely low. The subtype beta 2 was predominant in both lymph nodes and
      spleen. The results suggest that beta-adrenoceptors are present in mature cells
      in lymphoid tissues and are probably not involved in homing mechanisms.

PMID- 7813594
TI  - Metabotropic glutamate receptor agonist DCG-IV as NMDA receptor agonist in
      immature rat hippocampal neurons.
AB  - The electrophysiological action of (2S,1'R;2'R,3'R)-2-(2,3
      dicarboxycyclopropyl)glycine (DCG-IV) on the NMDA receptor was investigated with
      the help of concentration-jump experiments on freshly dissociated hippocampal CA1
      and CA3 neurons of rats. Inward currents elicited by a pulse of DCG-IV were
      insensitive to 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and could be blocked
      by D-(-)-2-amino-5-phosphonopentanoic acid (D-AP5) and magnesium and enhanced by
      glycine. The substance displayed cross-desensitization with NMDA but not with
      kainate or (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA).
      Dose-response curves showed that DCG-IV was weaker than NMDA but more potent than
      glutamate in eliciting agonist-gated currents. From these data we conclude that
      DCG-IV has to be used with caution as a tool for the investigation of
      metabotropic glutamate receptors.

PMID- 7813595
TI  - A polyamine binding site labelled with [3H]spermidine in developing human
      cerebellum.
AB  - Polyamines regulate cell division in developing brain. Neuronal membranes and the
      NMDA receptor have polyamine binding or functional sites. We have visualized
      [3H]spermidine binding in human cerebellum sections. Autoradiographs showed high
      specific [3H]spermidine binding in granule cell layer and low binding in
      molecular layer in neonate, infant and adult cerebellum which qualitatively
      resembled NMDA binding. Cerebellum from neonates and infants below 6 months had a
      further zone of dense [3H]spermidine binding in the external granule layer of
      migratory cells. This second zone may show a polyamine regulatory site for
      cerebellar development from fetal life to early infancy.

PMID- 7813597
TI  - Immune intervention in type I diabetes mellitus--current clinical and
      experimental approaches.
AB  - Experiments with animal models have proven that intervention protocols avoiding
      immunosuppressants can effectively prevent immune-mediated diabetes. These new
      approaches aim at either supporting the defence of islet cells against
      inflammatory attack or at modulating the type of the immune response to beta
      cells towards a more benign quality. Another approach is to reduce the exposure
      to putative diabetogenic dietary factors during infancy. All of the three
      strategies are presently tried in clinical studies.

PMID- 7813596
TI  - Muscarinic receptors in rat uterus.
AB  - The aim of this study was to characterise the muscarinic receptor present in the
      uterus of the virgin rat. Homogenate binding studies were undertaken using
      [3H]quinuclidinyl benzilate as the radioligand and atropine (10 microM) to
      determine non-specific binding. [3H]Quinuclidinyl benzilate binding was saturable
      with a Kd of 63 pM and a Bmax of 3 fmol/mg protein. The pKi values obtained using
      antagonists with high affinity for differing muscarinic receptor subtypes were
      pirenzepine, 6.2; hexahydrosiladifenidol, 6.9; AF-DX 116 (11-[[2
      [(diethylamino)methyl]-1-piperidinyl]acetyl]5,11-dihydro-6H - pyrido[2,3
      b][1,4]benzodiazepine-6-one), 7.0; and himbacine, 7.8. These findings suggest
      that muscarinic M2 receptors are present in rat uterus.

PMID- 7813598
TI  - Growth hormone therapy in adults: rationales, results, and perspectives.
AB  - This review outlines the present knowledge of the rationales, clinical aspects,
      and perspectives of a therapy with recombinant human growth hormone (rhGH) in
      adults. In patients with hypopituitarism the effects of rhGH replacement have
      been extensively studied. Recent clinical trials show that rhGH treatment
      improves most alterations of body composition and psychological performance, but
      many of the metabolic actions of GH remain equivocal. Although side effects after
      short-term administration are usually mild, the risks of severe long-term adverse
      effects are still uncertain. A supplementation with rhGH is also suggestive in
      advanced age and obesity, but the clinical results are controversial so far. The
      anabolic actions of rhGH were exploited in several recent trials including
      patients who were severely ill, malnourished, on chronic haemodialysis, or on
      total parenteral nutrition. Although nitrogen-sparing effects of GH have been
      demonstrated in most cases, the data do not indicate a clinical benefit in terms
      of reduced mortality, improved outcome, or accelerated recovery. Therefore,
      recommendations for the use of rhGH do not have any rationale in these patients
      yet. The efficacy of rhGH in the treatment of reproductive or immunological
      disorders remains elusive and needs further investigation. In conclusion, the
      application of rhGH is still an experimental therapy which should be performed
      under close observation in well-controlled clinical studies.

PMID- 7813599
TI  - Endocrine characterization of the new dopamine autoreceptor agonist roxindole.
AB  - Roxindole (5-Hydroxy-3-(4-phenyl-1,2,3,6-tetrahydropyridil-(1)-butyl)-indol) is a
      newly developed compound with a high dopamine autoreceptor agonistic potency at
      D2 receptors. Evaluation of roxindole for clinical purposes in psychiatric
      patients revealed that the substance has contrary to expectation merely
      negligible antipsychotic but considerable antidepressive effects. Interestingly
      it is nearly devoid of any side effects. To further characterize the endocrine
      effects, 1 mg roxindole was applied at 09:00 to 6 male volunteers and the effects
      compared to placebo. From 08:00 to 13:00 blood samples were drawn every 30 min.
      No effect on adrenocorticotropin and cortisol secretion was observed, neither
      mean plasma concentrations nor area values differed significantly. 90 min after
      roxindole administration an enhanced release of growth hormone could be observed,
      comparison of mean hormonal concentration revealed statistical significance (p <
      0.05). Also the area values differed significantly (roxindole vs. placebo mean +/
      SD 18.1 +/- 17.1 vs. 7.7 +/- 8.0 micrograms x h/l; p < 0.05). After roxindole
      also a pronounced reduction of prolactin plasma levels from 5.3 +/- 1.4
      micrograms/l to 1.1 +/- 0.4 microgram/l within 150 min could be observed. Mean
      plasma concentrations (p < 0.05) and area values differed significantly
      (roxindole vs. placebo mean +/- SD 14.8 +/- 13.5 vs. 34.4 +/- 18.1; p < 0.05).
      Roxindole had no effect on blood pressure parameters and heart rate. The major
      findings of the present exploratory study are, that roxindole has potent effects
      on the facilitation of growth hormone secretion and the inhibition of prolactin
      release. Both findings are complementary and point also to interesting
      postsynaptic dopamine receptor agonistic effects.

PMID- 7813600
TI  - Insulin-like growth factor I correlations to changes of the hormonal status in
      puberty and age.
AB  - IGF-I is considered to be one of the most important growth factors during
      puberty. Information concerning its correlation to thyroid hormones (T3, T4),
      adrenal and sex steroids is limited to puberty and the elderly. The presented
      study included 455 subjects (among them 259 children) ranging in age from newborn
      to 100 years. Serum IGF-I concentrations increase from childhood to the end of
      puberty (2 years earlier in girls). There are close positive correlations between
      IGF-I concentrations and age, height and weight and between IGF-I and estradiol
      or testosterone concentration in girls and boys respectively, and the DHEA-S
      level in boys during puberty. Correlations also exist with T3, aldosterone and 17
      OH-progesterone in boys and girls in the pubertal stages I-V and with T4 in
      stages I-IV. Compared to 20-30 year-old subjects IGF-I concentrations amounted to
      59% after 60 years, 43% in men and 54% in women after 70 years and 29% after 90
      years. It is suggested that increasing adrenal DHEA-S concentrations stimulate
      IGF-I synthesis and by means of gonadal steroidogenesis, increase the pubertal GH
      secretion and the further pubertal IGF-I increase. The low IGF-I concentrations
      in patients > 60 years reflect the more catabolic metabolism of the elderly.

PMID- 7813601
TI  - Regulation of interrenal secretion in the axolotl, Ambystoma mexicanum.
AB  - The regulation of corticosteroid secretion of the adrenal cortex (interrenal
      tissue) of axolotl (Ambystoma mexicanum) was studied using in vitro preparations
      of kidney containing interrenal tissue. Normally, 0.3-0.65 ng/5 min
      corticosterone and 0.15-0.3 ng/5 min aldosterone were released from the tissue.
      Regulatory peptides were effective in the following range: ACTH = arginine
      vasotocin > urotensin II > angiotensin II. They stimulate an elevation of
      corticosterone (plus 0.2-1 ng/5 min) and of aldosterone (plus 0.05-0.15 ng/5
      min). The three primary effector systems leading to second messengers, adenylate
      cyclase (forming cAMP), phospholipase C (forming InsP3 + DAG), and phospholipase
      A2 (liberating arachidonic acid) are involved in stimulation of biosynthesis. It
      can be suggested that the second messengers stimulate the biosynthesis at the
      level of the steps between pregnenolone and corticosterone ('3 beta
      hydroxysteroid-dehydrogenase etc.), because the release of corticosterone is more
      stimulated than aldosterone. This is different than the regulation of anuran
      interrenal tissue. Ca++ ions are involved in corticosterone secretion. Verapamil
      inhibits immediately the secretion of corticosteroids and elevation of external
      Ca++ stimulates the release. It is suggested that Ca++ mediates the secretion
      process itself. Metamorphosis does not change the response of the interrenal
      gland compared with the neotenic animal.

PMID- 7813602
TI  - Effect of morphine on hypothalamic catecholamine and serotonin level in relation
      to the stress-induced pituitary-adrenocortical activation in the rat.
AB  - The relationship between the hypothalamic catecholamine and serotonin level as
      well as the activation of the pituitary-adrenal axis was investigated after
      administration or morphine (MO) in the rat. Five mg/kg b. wt. of MO induced a
      significant increase in norepinephrine and a 78%, but insignificant, increase in
      dopamine level of the hypothalamus within 60 min without changing corticosterone
      secretion. Electric footshock, in addition to elevating hypothalamic
      norepinephrine and dopamine levels, significantly increased the pituitary
      adrenocortical response in the MO pretreated rats. Five mg/kg b. wt. of MO, or
      electric footshock alone did not influence the hypothalamic serotonin level
      within 60 min, but the hypothalamic serotonin level decreased significantly in
      the MO pretreated, electrically shocked animals. We conclude, that 1) low dose of
      MO may induce changes of the hypothalamic catecholamine levels without
      influencing pituitary-adrenocortical activation. 2) enhanced hypothalamic
      catecholamines by MO did not prevent increasing pituitary-adrenocortical response
      elicited by stress. It appears, that the hypothalamic catecholaminergic mechanism
      which may inhibit ACTH release during stimulation does not function in the MO
      treated rats.

PMID- 7813603
TI  - Okadaic acid indicates a major function for protein phosphatases in stimulus
      response coupling of RINm5F rat insulinoma cells.
AB  - Stimulus-induced insulin secretion involves the activation of several protein
      kinases within the beta cell. Most prominent are protein kinase A, protein kinase
      C and calcium/calmodulin-dependent protein kinases. Protein kinase action is
      functionally antagonized by protein phosphatases. The four ubiquious
      serine/threonine protein phosphatases are termed PP-1, PP-2A, -2B and -2C. PP-1
      and PP-2A are in vivo parts of major protein complexes. These complexes
      presumably regulate the phosphatase activity and direct the enzyme to its site of
      action. Therefore, PP-1 and -2A could play an important role in controlling
      intracellular signal transmission. Two different toxins, okadaic acid and
      calyculin A, both from marine invertebrates, were recently discovered and
      identified as potent and highly specific inhibitors of PP-1 and PP-2A. Both
      compounds emerged as very useful tools for studying intracellular phosphorylation
      events. We took advantage of these substances to investigate the significance of
      protein phosphatase action in stimulus-induced insulin secretion. To avoid major
      complexity, we confined our study to the cAMP and the phosphoinositide signal
      pathway. Okadaic acid alone evoked virtually no secretory response. cAMP
      dependent secretion was markedly enhanced by 1 microM okadaic acid. The
      stimulatory effect of okadaic acid was strongly dependent on the concentration of
      cAMP analoga. In contrast, insulin release caused by the cholinergic agonist
      carbachol was not influenced by okadaic acid. Calyculin A (10 nM) slightly
      increased cAMP-induced secretion, but its high toxicity prohibited accurate
      interpretation of the data. Our findings support the idea that serine/threonine
      phosphatases act as important regulators in stimulus response coupling.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7813604
TI  - Ovarian LH/hCG receptors and plasma level of LH,17-beta estradiol and
      progesterone in gonadotropin--induced PCO syndrome in rats.
AB  - The aim of this work was to investigate the morphologic changes, LH/hCG receptor
      content in the ovaries and plasma levels of LH, progesterone and estradiol of
      hypo--and hyperthyroid rats injected with PMSG and hCG. The hypothyroid state was
      induced by thyreoidectomy (Tr-X) and the hyperthyroid condition by injections of
      40 micrograms L-thyroxine daily during 21 days (T4). Gonadotropins were injected
      during 14 days in daily doses: PMSG--5 i.u. and hCG--10 i.u. The following 8
      groups (n = 10-20) were established: control (euthyroid, no treatment), Tr-X,
      PMSG + hCG, Tr-X + hCG, Tr-X + PMSG, Tr-X + PMSG + hCG, T4 and T4 + PMSG. At the
      end of experiments rats were sacrificed, ovaries weighed, macroscopically
      inspected and concentration of LH/hCG receptors was estimated. In blood plasma
      the level of LH, progesterone and 17-beta estradiol was also analysed. The
      experiments showed that injections of PMSG alone, or PMSG + hCG in eu-or
      hypothyroid rats, appear the most effective in induction of PCO syndrome in rats.
      Low levels of thyroid hormones sensitized the ovaries to gonadotropin action, but
      a hyperthyroid status diminished or inhibited this response. Thyroid function is
      also essential in production of LH/hCG receptors in the ovaries. In hypothyroid
      animals the amount of these receptors was greatly increased, while in
      hyperthyroid animals they decreased. The level of plasma LH, progesterone, and
      estradiol showed insignificantly differences and various inconsiderable
      deviations from norm. These differences were not dependent on large doses of
      gonadotropins, altered thyroid function, or on cystic or luteinizing changes in
      the ovary.

PMID- 7813605
TI  - Plasma levels of benperidol, prolactin, and homovanillic acid after intravenous
      versus two different kinds of oral application of the neuroleptic in
      schizophrenic patients.
AB  - Plasma levels of prolactin (PRL) and the butyrophenone neuroleptic benperidol
      (BPD) were closely followed 0 to 48 h after acute application of 6 mg BPD as
      intravenous injection, orally as liquid, and orally as tablets in 12
      schizophrenic patients using a partially randomized cross over design. Drug
      concentrations showed application specific pharmacokinetic behavior with complete
      elimination within 48 h. All three applications led to a biphasic PRL response
      with pronounced initial plasma PRL peaks returning to baseline levels within 48
      h. The results suggest that after acute neuroleptic challenge BPD plasma levels
      as low as 2-3 ng/ml can be sufficient for complete depletion of pituitary PRL
      stores. This initial peak was followed by a PRL plateau about twice above
      pretreatment values indicating doubling of the PRL synthesis and secretion
      independent of supraeffective actual BPD concentrations. The PRL plateau
      persisted as long as BPD concentrations were above those levels which triggered
      the initial PRL response. As compared with the time of maximum concentrations
      (tmax) for BPD, the PRL tmax was later after i.v. injection, equal after liquid
      application, and earlier after tablet administration leading to pronounced
      application specific differences in shape, direction, and position of resulting
      hysteresis curves. Plasma levels of homovanillic acid (HVA) were not affected by
      BPD treatment. The PRL and HVA levels registered after acute doses of BPD
      indicated that the hormone responses were most likely the result of acute
      depletion of PRL stores and subsequent stimulation of hormone synthesis whereas
      it seemed unlikely that dopaminergic activities were relevant.

PMID- 7813606
TI  - Molecular cloning of a cDNA encoding for the GLP-1 receptor expressed in rat
      lung.
AB  - Recent data revealed the existence, localization and possible function of
      specific receptors for glucagon-like peptide 1 (7-36) amide (GLP-1) in rat lung.
      This receptor has different biochemical features than the GLP-1 receptor in
      endocrine pancreas. Therefore, we aimed to clone the lung receptor cDNA in order
      to analyze whether biochemical and functional diversity of the GLP-1 receptors in
      lung and pancreas is based upon genetic differences. A cDNA library from rat lung
      in a lambda gt11 vector was screened with a cDNA probe coding for the rat
      pancreas GLP-1 receptor. Thereby, we found a lung GLP-1 receptor cDNA which shows
      nearly complete homology to the pancreatic beta-cell receptor cDNA. Only one base
      exchange occurred at base 1 of a codon at position 977 resulting in a change of
      valine residue for isoleucine at position 323 of the amino acid sequence within
      the fifth transmembrane region. Northern blot hybridization identified
      transcripts at 2.7, 3.4, and 3.6 Kb. Expression of the recombinant lung GLP-1
      receptor cDNA in CHO cells displayed a pharmacological profile similar to that
      seen with cells expressing the beta-cell derived cDNA. Therefore, we conclude
      that tissue-specificity for GLP-1 receptors is based upon posttranslational
      modifications of the receptor protein (for example glycosilation) or alternative
      splicing of primary transcripts and not on variations within the coding sequence
      of the receptor gene.

PMID- 7813607
TI  - Congenital adrenal hyperplasia with 47, XXY Klinefelter syndrome.
AB  - We describe here a unique case of congenital adrenal hyperplasia (CAH)
      accompanied by Klinefelter syndrome. A Japanese boy was diagnosed as having CAH
      caused by 21-hydroxylase deficiency at birth, but was untreated thereafter until
      age 10. In the meantime he showed marked acceleration in somatic growth with
      sexual precocity by age 9, at which time growth completely stopped. During
      regular follow-ups at our clinic and steroid treatment after age 10, he was
      recognized as having bilateral small and firm testes. A chromosomal examination
      and a testicular biopsy revealed a complication of 47, XXY Klinefelter syndrome
      with CAH. Association of these two diseases has not been reported so far, and the
      present case is the first one to our knowledge.

PMID- 7813608
TI  - Insulin-induced hypoglycemia stimulates gluconeogenesis from 14C-lactate
      independently of glucagon and adrenaline releases in rats.
AB  - Correlation between blood glucose, glucagon and adrenaline levels and
      gluconeogenesis was studied during the recovery from insulin-induced hypoglycemia
      in rats. Rats, overnight fasted, were intravenously injected with 40 microCi/kg
      of [U-14C]-lactate and 1 U/kg of porcine insulin under an anesthesia with
      pentobarbital sodium. Blood samples were drawn via the peripheral vein at 0, 5,
      10 and 20 min. Plasma insulin level was 617 +/- 115 microU/ml at 5 min. Plasma
      glucose level was significantly decreased at 5 min (2.7 +/- 0.3 mM at 5 min v.s.
      4.3 +/- 0.2 mM at 0 min, P < 0.01). Plasma glucagon and adrenaline did not
      significantly respond at 5 min, and then rised. Specific radioactivity of plasma
      [1-14C]-glucose was significantly higher at 5 and 10 min in the insulin-injected
      rat than the saline-injected rat (204 +/- 34 v.s. 130 +/- 14 d.p.m./mumol at 5
      min, P < 0.01; 275 +/- 32 v.s. 186 +/- 16 d.p.m./mumol at 10 minm P < 0.01).
      These results suggest that lowering of blood glucose level stimulates
      gluconeogenesis independently of the release of counter-regulatory hormones in
      insulin-induced hypoglycemia.

PMID- 7813609
TI  - Correlation between complementation group for immortality and the cellular
      distribution of mortalin.
AB  - The dominance of cellular senescence over the immortal phenotype has been
      demonstrated by cell fusion experiments utilizing human and mouse cells.
      Mortalin, a novel 66-kDa member of the murine hsp70 family of proteins, has
      recently been identified as a marker of the mortal phenotype by virtue of its
      characteristic cytosolic distribution in mortal cells. Here we report the
      mortalin immunostaining observations on 21 human cell lines. These cell lines
      have previously been assigned by somatic cell hybridization analysis to one (18
      lines) or more than one (3 lines) of the four complementation groups (A, B, C,
      and D) for immortalization. Four patterns of mortalin immunostaining were
      observed: granular-juxtanuclear cap, granular-gradient from nuclear to cell
      membrane, granular-juxtanuclear arch, and fibrous-perinuclear. In 17 of 18 cell
      lines assigned to a single complementation group, the mortalin staining
      corresponded with the complementation group. In two of the three cell lines
      previously assigned to multiple complementation groups, the mortalin staining
      corresponded to one of the assigned groups. Two cell lines, however, exhibited
      staining patterns which did not match to their assigned complementation groups.
      The basis of correlation between cellular distribution of mortalin and the
      complementation group remains unclear at present. However, the data (i) suggest
      that the intracellular distribution of mortalin can be used to distinguish mortal
      and immortal cells, confirming the association of mortalin with senescence; (ii)
      provide supportive evidence for the existence of at least four different pathways
      of immortalization in human cells; and (iii) indicate that mortalin is involved
      in processes that result in immortalization.

PMID- 7813610
TI  - Transforming growth factor-beta 1 has both promoting and inhibiting effects on
      induction of DNA synthesis in human fibroblasts.
AB  - Growth-arrested human normal fibroblasts, TIG-1, initiated DNA synthesis
      following addition of epidermal growth factor (EGF). Transforming growth factor
      beta 1 (TGF-beta 1) by itself had no effect on induction of DNA synthesis. When
      EGF and TGF-beta 1 were added simultaneously to growth-arrested TIG-1 cells,
      induction of DNA synthesis was enhanced compared with that by EGF alone.
      Contrarily, when TGF-beta 1 was added earlier than 2 h or later than 2 h of EGF
      addition, induction of DNA synthesis was prevented. Induction of DNA synthesis by
      EGF was insensitive to pertussis toxin (PT, an inhibitor of Gi protein) and to
      staurosporine (a protein kinase inhibitor). The promoting effect of TGF-beta 1 on
      DNA synthesis was PT-insensitive and staurosporine-insensitive. Contrarily,
      inhibitory activity of TGF-beta 1 on DNA synthesis was PT-sensitive and
      staurosporine-insensitive. These studies suggest that the effect of TGF-beta 1 is
      to promote or to inhibit induction of DNA synthesis by EGF expressed through
      different signal transduction processes in the same cell.

PMID- 7813611
TI  - Regulation of endothelial cell morphogenesis by integrins, mechanical forces, and
      matrix guidance pathways.
AB  - Basement membrane matrix is known to induce human endothelial cells to form cord
      like structures that mimic those observed during early angiogenesis in vivo.
      Using this model, blocking antibody studies revealed a major role for the alpha 6
      beta 1 integrin in cord formation. During this process, two alterations in the
      Matrigel structure were observed which suggested a mechanism for the precision of
      cord formation. First, Matrigel contracted and lifted off an agarose support and
      second, linear distortions became visible in the Matrigel that correspond to the
      migration pathways of endothelial cell processes. These pathways, which we have
      termed "matrix guidance pathways," appear to result from the generation of
      mechanical tension between endothelial cells. The above data support the concept
      that endothelial cell guidance during morphogenetic events could be controlled by
      the ability of these cells to exert mechanical forces on the surrounding
      extracellular matrix to create pathways for migration.

PMID- 7813612
TI  - Essential role of protein phosphorylation in nuclear transport.
AB  - We have investigated a possible role for protein phosphorylation in nuclear
      transport in semi-intact cells, prepared by digitonin permeabilization of rat F
      111 fibroblasts. Treatment of semi-intact cells with alkaline phosphatase
      abolished the import of nuclear transport substrates, namely, signal peptide
      albumin conjugates, as well as their signal-dependent binding at the nuclear
      pores, but did not affect the morphology of the cells, in particular their
      cytoskeletal network. Authentic transport and functional binding of the
      karyophilic protein at the nuclear envelope could be restored by incubation of
      phosphatase-treated cells with cytosol enriched in protein kinase C or with
      purified protein kinase A (catalytic subunit). Restoration of transport was
      blocked by specific inhibitors of these kinases. Since the protein
      phosphorylation required for nuclear transport appeared to be a reasonably stable
      modification, characterization of the phosphorylated proteins was attempted in
      kinase reactions with radiolabeled ATP. Two proteins of 60-62 kDa were the
      predominant substrates phosphorylated by both protein kinase C and protein kinase
      A under conditions wherein nuclear transport was restored. Our results suggest a
      requirement for phosphorylation of one or more proteins for binding of a
      karyophilic protein at the nuclear envelope.

PMID- 7813613
TI  - Density-dependent induction of apoptosis by transforming growth factor-beta 1 in
      a human ovarian carcinoma cell line.
AB  - Transforming growth factor-beta 1 inhibited proliferation of a human ovarian
      carcinoma cell line (NIH-OVCAR-3). The inhibition of NIH-OVCAR-3 cell
      proliferation was accompanied by a decrease in clonogenic potential, evidenced by
      the reduced ability of TGF-beta 1-treated NIH-OVCAR-3 cells to form colonies on a
      plastic substratum. This rapid decrease of clonogenic potential, which was
      detected 6 h after addition of TGF-beta 1 was dose-dependent (IC50 = 4 pM).
      Fluorescence microscopy of DAPI-stained cells supported by electron-microscopic
      examination showed that TGF-beta 1 induced chromatin condensation and nuclear
      fragmentation. In addition, oligonucleosomal-sized fragments were detected in the
      TGF-beta 1-treated cells. These features indicated that TGF-beta 1 induced NIH
      OVCAR-3 cell death by an apoptosis-like mechanism. This TGF-beta 1 apoptotic
      effect was subject to modulation by cell density. It was observed that an
      increase in cell density (up to 20 x 10(3) cells/cm2) protected NIH-OVCAR-3 cells
      against apoptosis induced by TGF-beta 1. Conditioned medium from high-density
      cultures of NIH-OVCAR-3 cells did not inhibit apoptosis induced by TGF-beta 1 on
      NIH-OVCAR-3 cells cultured at low density, suggesting that the protective effect
      of cell density was not related to the cell secretion of a soluble survival
      factor.

PMID- 7813614
TI  - The effect of sterols and brefeldin A on protein degradation in UT-1 cells.
AB  - UT-1 cells, a mutant Chinese hamster ovary (CHO) cell line induced to produce an
      abundance of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR),
      were used to determine the effects of sterols and brefeldin A on the degradation
      of this enzyme. Brefeldin A has been shown to cause retention of proteins in and
      relocation of proteins to the endoplasmic reticulum (ER). UT-1 cells were
      incubated with (a) sterols only (12 micrograms/ml cholesterol and 0.2
      microgram/ml 25-hydroxycholesterol), (b) sterols and brefeldin A (0.5
      microgram/ml), and (c) brefeldin A only. Western blot analysis showed that
      incubation with sterols and brefeldin A decreased HMGR levels more slowly than
      incubation with sterols alone over the first 24-36 h of incubation; however, the
      rates were not significantly different. By 48 h of incubation, HMGR had decreased
      to a level comparable to that found when cells were incubated in sterols only.
      Incubation with brefeldin A alone did not cause a decrease in HMGR over the same
      48-h time period. HMGR was undetectable in parental CHO cells under all of the
      conditions described. Indirect immunofluorescence microscopy revealed a pattern
      of tight, perinuclear staining with sterol incubation. After 48 h in sterols,
      HMGR staining was uniformly decreased throughout the cytoplasm. This change in
      staining pattern is also observed during incubation of UT-1 cells with sterols
      and brefeldin A. Incubation for 48 h with brefeldin A alone had no effect on the
      tight perinuclear pattern originally observed. Diffuse, faint staining of CHO
      cells under all conditions served as a negative control. The results of these
      experiments indicated that brefeldin A, and therefore retention of proteins in
      the ER, does not interfere with the degradation of HMG CoA reductase. Despite the
      presence of brefeldin A, sterol-mediated dispersal and degradation of the
      crystalloid ER (CER) continued in UT-1 cells. Lack of brefeldin A sensitivity
      implied that the mechanism for CER dissolution was distinct from previously
      described mechanisms for ER to Golgi transport.

PMID- 7813615
TI  - Reevaluation of the role of de novo protein synthesis in rat thymocyte apoptosis.
AB  - In this study, the role of de novo protein synthesis in rat thymocytes undergoing
      apoptosis after treatment with methylprednisolone (MPS), ionomycin, or
      thapsigargin was evaluated using several inhibitors of protein synthesis
      (cycloheximide, emetine, and puromycin). Cycloheximide (1 microgram/ml) inhibited
      DNA cleavage in rat thymocytes treated with thapsigargin, MPS, and ionomycin by
      91, 94, and 96%, respectively, and reduced [3H]leucine incorporation into
      cellular proteins by 87, 85, and 84%, respectively. Emetine (300 nM) inhibited
      protein synthesis in thymocytes to an equivalent level but reduced DNA cleavage
      by only 49, 43, and 57% in cells treated with thapsigargin, MPS, or ionomycin,
      respectively. More than threefold higher concentrations of emetine (1 microM)
      were required to suppress DNA fragmentation to a similar extent as observed with
      cycloheximide. Puromycin at a concentration (5 micrograms/ml) that reduced
      [3H]leucine incorporation by > 80% enhanced DNA cleavage in thymocytes treated
      with thapsigargin, MPS, or ionomycin. By itself, puromycin (0.1-5 micrograms/ml),
      but not cycloheximide or emetine, induced DNA fragmentation in thymocytes with
      the concomitant inhibition of protein synthesis. An analogue of puromycin,
      puromycin aminonucleoside, which has no effect on protein synthesis, did not
      induce DNA fragmentation in thymocytes and did not prevent thymocyte apoptosis
      triggered by other agents. Both cycloheximide and emetine dose-dependently
      reduced thymocyte DNA cleavage induced by puromycin despite marked inhibition of
      protein synthesis by puromycin itself. At high concentration, puromycin (50
      micrograms/ml) was less efficient in causing DNA cleavage when added alone and
      markedly inhibited chromatin degradation induced by thapsigargin, MPS, or
      ionomycin. Prolonged treatment (24 h) of thymocytes with any one of the different
      translational inhibitors resulted in extensive DNA fragmentation. Similarly, the
      protective effect of these inhibitors on DNA degradation in thymocytes induced by
      thapsigargin, MPS, or ionomycin diminished after 24 h. The present study
      demonstrates a lack of correlation between inhibition of protein synthesis and
      prevention of DNA fragmentation in thymocyte apoptosis and suggests that the
      effects of translational inhibitors on thymocyte apoptosis are nonspecific, and
      that they may delay the onset of apoptosis rather than prevent it.

PMID- 7813616
TI  - The effect of space and parabolic flight on macrophage hematopoiesis and
      function.
AB  - We used weak electric fields to monitor macrophage spreading in microgravity.
      Using this technique, we demonstrated that bone marrow-derived macrophages
      responded to microgravity within 8 s. We also showed that microgravity
      differentially altered two processes associated with bone marrow-derived
      macrophage development. Spaceflight enhanced cellular proliferation and inhibited
      differentiation. These data indicate that the space/microgravity environment
      significantly affects macrophages.

PMID- 7813617
TI  - Formation of apoptotic bodies is associated with internucleosomal DNA
      fragmentation during drug-induced apoptosis.
AB  - The onset of apoptosis is often coincident with internucleosomal DNA
      fragmentation or ladders which are considered a hallmark of the process. However,
      several studies have indicated that MOLT-4 human lymphoblastoid cells exposed to
      various agents, including VP16, display some apoptotic characteristics in the
      absence of either internucleosomal ladders or production of apoptotic bodies. The
      present study records that, in the presence of aurintricarboxylic acid (ATA),
      internucleosomal ladders were detected in DNA isolated from VP16-treated MOLT-4
      cells; a paradoxical result in view of inhibition by ATA of nuclease activity in
      cell free preparations. The activity of ATA in mediating genomic fragmentation
      was dose- and time-dependent. Moreover, addition of ATA to VP16-treated MOLT-4
      cells also resulted in production of apoptotic bodies, this effect being
      quantified by morphological examination and flow cytometry. Detection of ladders
      and apoptotic bodies after addition of ATA was not attributable to increased
      toxicity in cells exposed to the combined treatment relative to VP16 alone. A
      similar response, that is the appearance of both internucleosomal fragmentation
      and apoptotic bodies, occurred after exposure of MOLT-4 cells to the mitotic
      inhibitor podophyllotoxin. The consistent association between internucleosomal
      fragmentation of DNA and formation of apoptotic bodies exhibited during death of
      MOLT-4 cells, insofar as both characteristics are either present or absent
      following different agents, suggests interdependence.

PMID- 7813619
TI  - Nonrandom arrangement of bovine satellite I DNA within the interphase nucleus of
      Madin-Darby bovine kidney cells.
AB  - The distribution of bovine satellite DNA was examined in Madin-Darby bovine
      kidney cells for each hour of interphase. Cells were grown on coverslips and
      probed using biotinylated cloned fragments of bovine satellite I DNA.
      Hybridization was detected using a streptavidin-alkaline phosphatase conjugate.
      Cells were projected onto a grid of fixed dimensions and the distribution of
      hybridization signal was recorded. A chi 2 analysis of fit compared this
      distribution of signals to a random distribution generated from the poisson
      distribution. Nuclear localization of bovine satellite I DNA was found to be
      nonrandom throughout interphase except at the G1/S border and S = 6 h. Moreover,
      distinct patterns of hybridization were also observed at specific times during
      interphase.

PMID- 7813618
TI  - Analysis of the proliferative response to lysophosphatidic acid in primary
      cultures of mammary epithelium: differences between normal and tumor cells.
AB  - The effect of lysophosphatidic acid (LPA) on the proliferation of normal and
      tumor mouse mammary epithelial cells in primary, serum-free, collagen gel cell
      culture was evaluated. LPA stimulated the growth of normal mammary epithelial
      cells from mature virgin mice. The growth of pregnancy-dependent tumors (PDT) was
      generally stimulated, although the response was attenuated in some of these
      tumors compared to normal cells. In contrast, the growth of 70% of ovarian
      independent tumors (OIT) was inhibited by LPA; the remainder were unaffected. LPA
      stimulated cAMP accumulation and phosphoinositide (PI) hydrolysis in normal, PDT,
      and OIT. Thus, the regulation of adenylyl cyclase and PI-specific phospholipase C
      by LPA is similar in normal and tumor cells. Pertussis toxin (PT) partially
      inhibited LPA-stimulated growth in normal cells but did not affect LPA-stimulated
      PI hydrolysis or cAMP accumulation. Thus, PT-sensitive and -insensitive
      proliferative pathways are activated. PT also inhibited LPA-stimulated growth of
      PDT but generally had no effect on the growth of OIT. These results show that the
      mitogenic response to LPA is attenuated in the hormone-dependent phenotype and
      switches to growth inhibition in hormone-independent tumors. Furthermore, LPA
      stimulates multiple signal transduction pathways mediated by PT-sensitive and 
      insensitive G proteins. The PT-sensitive pathways are not tightly coupled to the
      proliferative response to LPA in tumor cells. These data suggest that alterations
      in G protein function may occur during tumor progression.

PMID- 7813620
TI  - Terminal differentiation of chondrocytes in culture is a spontaneous process and
      is arrested by transforming growth factor-beta 2 and basic fibroblast growth
      factor in synergy.
AB  - At Day 17 of in ovo development, chondrocyte hypertrophy including synthesis of
      collagen X takes place in a limited region within the cranial part of chick
      embryo sternum. Here we analyze in suspension culture the differences in response
      to single growth factors of chondrocytes derived from the cranial part versus
      cells derived from the caudal part. Cells from either part were cultured
      separately without serum in the presence of insulin-like growth factor-1,
      transforming growth factor beta 2, basic fibroblast growth factor, or thyroid
      hormones. In culture, chondrocytes derived from the cranial part of sterna from
      14- to 18-day-old chicken embryos become hypertrophic and initiated the synthesis
      of collagen X and alkaline phosphatase. These processes were enhanced by anabolic
      diffusible signals, such as those contained in fetal bovine serum, insulin-like
      growth factor-1, or thyroxine. Cells derived from the caudal part lack this
      capacity and, instead, prevented hypertrophy of cranial cells in cocultures,
      presumably by secreting diffusible signals. As candidate molecules, we have
      identified transforming growth factor beta 2 and basic fibroblast growth factor,
      which both were released by chondrocytes. Synergistic action of transforming
      growth factor beta 2 and basic fibroblast growth factor was required to suppress
      insulin-like growth factor-1-stimulated maturation of cranial chondrocytes in
      culture.

PMID- 7813622
TI  - Molecular characterization of a type I serine-threonine kinase receptor for TGF
      beta and activin in the rat pituitary tumor cell line GH3.
AB  - GH3 pituitary tumor cells have surface receptors for transforming growth factors
      beta (TGF-beta s) and activins/inhibins. GH3 cell mRNA was screened by a novel
      reverse transcriptase-polymerase chain reaction technique with primers for
      receptor serine-threonine kinases. We isolated rat homologs of previously
      identified clones for type I (ALK-2 and ALK-5) and type II (ActRII, TGF-beta RII)
      activin and TGF-beta receptors, together with a novel clone, whose full-length
      version was isolated from a GH3 cell cDNA library. Named B1, it encodes a 505
      amino-acid protein belonging to the family of type I receptor serine/threonine
      kinases. The kinase domain of B1 exhibits 90% identity to that of the TGF-beta
      type I receptor. B1 mRNA is expressed not only in pituitary cells but also in all
      other cells and tissues examined. B1 protein can be expressed on the cell
      surface, but cannot bind ligand unless a type II receptor is also present. When
      coexpressed with the type II receptors specific for TGF-beta or activin, B1 can
      be efficiently cross-linked to either ligand, suggesting that it can form
      heteromeric complexes with both type II receptor subunits.

PMID- 7813621
TI  - Maintenance of vascular endothelial cell-specific properties after
      immortalization with an amphotrophic replication-deficient retrovirus containing
      human papilloma virus 16 E6/E7 DNA.
AB  - Primary human vascular endothelial cells were immortalized by the integration of
      a single DNA copy of an amphotrophic, replication-deficient retrovirus containing
      the E6/E7 genes of human papilloma virus. To date, the resulting cell lines,
      designated EC-RF7 and EC-RF24, have been cultured for more than 1 year. The cell
      lines have retained a diploid karyotype, display no abnormalities, and are able
      to grow in a polar mode. Analysis of the EC-RF cell lines by indirect
      immunofluorescence, using an extensive panel of monoclonal antibodies, showed
      expression of endothelial cell-specific soluble (von Willebrand factor) and
      surface-bound antigens (endoglin, PCAM-1) indistinguishable from that of primary
      cells. In addition, the expression of the markers CD9, 13, 14, 29, 36, 40, 51,
      and 55 that are not restricted to endothelial cells was also similar for the
      immortalized and the primary endothelial cells. Immortalization did not alter the
      expression of the surface adhesion molecules E-selectin, VCAM-1, and ICAM-1 nor
      transmigration of neutrophils. The regulation of extracellular proteolytic
      activity by EC-RF24 was established by measuring both the induction of functional
      tissue factor (promotion of Factor Xa generation) and the functional deposition
      of plasminogen activator inhibitor 1 in the subendothelial matrix (SDS-resistant
      complex formation with thrombin). Finally, the biosynthesis of the endothelial
      cell-specific von Willebrand factor was studied in detail in the EC-RF24 cell
      line and the results were compared with those of primary endothelial cells.

PMID- 7813623
TI  - Thiophosphorylated RCM-lysozyme, an active site-directed protein tyrosine
      phosphatase inhibitor, inhibits G2/M transition during mitotic cell cycle and
      uncouples MPF activation from G2/M transition.
AB  - Microinjection of thiophosphotyrosylated RCM-lysozyme (TRCML), a potent and
      specific inhibitor of protein tyrosine phosphatases (PTPs) into sea urchin
      (Lytechinus pictus) eggs prior to fertilization inhibited the first zygotic cell
      division in a concentration-dependent fashion. Microinjection of TRCML at varying
      times after fertilization indicated that at least one site of action is late in
      the first cell cycle near the G2/M boundary. In order to further study the
      mechanism for the TRCML effect, a cell-free cell cycling system prepared from
      electrically activated Xenopus eggs was used. The addition of TRCML to cycling
      extracts delayed the entrance and progression of extracts through mitosis, as
      indicated by the inhibition of chromatin condensation, nuclear envelope
      breakdown, M-phase-promoting factor (MPF) inactivation, and cyclin degradation.
      Surprisingly, TRCML did not inhibit MPF activation. These results suggest that
      (1) the target(s) of TRCML lies in late G2- or early M-phase before the onset of
      metaphase, (2) TRCML uncouples MPF activation from progression through M-phase,
      and (3) there is a potential involvement of a novel PTP(s) in the control of the
      cell cycle which may act either downstream of the MPF activation or alternatively
      in an additional but essential mitotic pathway that is parallel to the MPF
      activation pathway.

PMID- 7813624
TI  - Distinct mechanisms for Ca2+ entry induced by OKT3 and Ca2+ depletion in Jurkat T
      cells.
AB  - Ca2+ influx triggered by antigen binding to T cell receptors (TCR) is an early
      event in T cell activation. An additional Ca2+ influx induced by depletion of
      intracellular Ca2+ (CDCI) has been characterized in human Jurkat T cells that is
      both temporally and mechanistically distinct from TCR-mediated Ca2+ influx
      (TCRCI). Both TCRCI and CDCI were insensitive to voltage-gated Ca2+ channel
      antagonists (e.g., nifedipine, verapamil, and omega-conotoxin G) and pertussis
      toxin, yet were voltage-sensitive and inhibited by SKF 96365 (a receptor-gated
      Ca2+ channel blocker) and cholera toxin. However, TCRCI but not CDCI was
      associated with a significant increase in inositol phosphate (IP chi) levels and
      inhibited by phorbol ester, while CDCI but not TCRCI was inhibited by Sr2+,
      forskolin (FSK), and 1,9-dideoxy FSK in a cAMP-independent fashion. Moreover, TCR
      stimulation did not deplete thapsigargin-sensitive Ca2+ stores, suggesting that
      TCRCI is not merely a consequence of Ca2+ depletion. These results indicate that
      Ca2+ entry following the depletion of intracellular Ca2+ stores or TCR
      stimulation occur through distinct cellular mechanisms coexisting in Jurkat T
      cells.

PMID- 7813625
TI  - The cytoplasmic domain of alpha 6A integrin subunit is an in vitro substrate for
      protein kinase C.
AB  - We have investigated whether the cytoplasmic domain of alpha 6A integrin subunit
      can be phosphorylated by Ser/Thr kinases using synthetic peptides as in vitro
      substrates. This domain was phosphorylated by protein kinase C (PKC) and cyclic
      AMP-dependent kinase (protein kinase A, PKA) but not by mitogen-activated protein
      kinase. While Ser1041 has been shown to be phosphorylated in PMA-stimulated cells
      in vitro, Ser1048 was phosphorylated by PKA. Furthermore pharmacological agents
      which induce a rise in cyclic AMP concentration failed to stimulate the
      phosphorylation of the alpha 6A cytoplasmic domain in intact cells. These results
      suggest that PKC, but not PKA, is involved in the physiological phosphorylation
      of the alpha 6A integrin subunit.

PMID- 7813626
TI  - Nucleoplasmin-targeted aequorin provides evidence for a nuclear calcium barrier.
AB  - The Ca(2+)-activated photoprotein aequorin has been targeted to the nucleus of
      live cells by engineering nucleoplasmin, a nuclear structural protein from
      Xenopus laevis, onto the amino terminus. Successful targeting of the apoprotein
      was demonstrated by immunolocalization and selective permeabilization of the
      plasma membrane. Functional protein was reconstituted in live cells by incubation
      with coelenterazine. The effect of elevating cytosolic Ca2+ on nuclear Ca2+ was
      investigated in populations of live COS7 cells expressing either cytosolic
      aequorin or nuclear aequorin. Incubation of cells with ionomycin, in the absence
      of external Ca2+, released Ca2+ from internal stores causing an increase in
      chemiluminescent light emission from cytosolic aequorin but not nuclear aequorin.
      Nonagonist-dependent movement of Ca2+ across the plasma membrane, induced by the
      membrane attack complex of complement, causes a large increase in cytosolic Ca2+
      which triggered 95% of cytosolic aequorin but only 50-60% of nuclear aequorin.
      These results provide clear evidence for a nucleocytoplasmic barrier to Ca2+.

PMID- 7813627
TI  - Developmental stage-specific cellular responses to vitamin D and glucocorticoids
      during differentiation of the osteoblast phenotype: interrelationship of
      morphology and gene expression by in situ hybridization.
AB  - Fetal rat calvarial-derived osteoblasts, in vitro, undergo a developmental
      sequence of events leading to bone tissue-like organization and osteoblast
      differentiation. Previous studies have documented temporal expression of genes
      reflecting stages of osteoblast phenotype development in relation to tissue
      organization. Two steroid hormones are known to modify the developmental
      sequence; 1,25(OH)2D3 can block differentiation when added to proliferating
      cells, while glucocorticoid addition to proliferating cultures increases the
      population of cells competent to produce a bone-like matrix and accelerates the
      differentiation time course. We have addressed the mechanisms contributing to
      these observations at the single cell level by analysis of a growth-related gene
      (H4 histone which is coupled with DNA synthesis) and matrix-associated genes
      (collagen, osteopontin, and osteocalcin) in hormone-treated cells. Our results
      demonstrate (1) a window of responsiveness for modifications in phenotype
      development; (2) distinct morphological changes and selective modifications in
      gene expression in response to both hormones as a function of whether the cell is
      proliferating or differentiated; and (3) location of the cell with respect to the
      mineralized nodule was a contributing factor to the levels of gene expression and
      hormonal responses. In response to vitamin D, surface osteoblasts associated with
      the nodules became flattened, elongated, and aligned, reminiscent of a bone
      lining cell. In glucocorticoid-treated cultures, proliferating cells became
      cuboidal and nodule-associated differentiated cells were approximately one-third
      the size of control osteoblasts. We also find subsets of hormone-responsive cells
      in the proliferating cultures in response to glucocorticoid but not vitamin D. In
      postproliferative cultures, both hormones increased osteocalcin mRNA in the more
      differentiated osteoblasts associated with the mineralized matrix but no
      induction occurred in monolayer internodular cells. Osteopontin was induced by
      glucocorticoid in a larger population of cells. Thus, our studies at the single
      cell level show selective morphological changes and changes in the level of gene
      expression supporting the hypothesis that hormones have differential effects on
      osteoblasts in relation to their stage of phenotype development.

PMID- 7813628
TI  - Immunoaffinity purification of migratory mouse primordial germ cells.
AB  - Primordial germ cells (PGCs) are the earliest identifiable germ cells in the
      embryo. It has not previously been possible to purify PGCs from mammalian embryos
      at early stages of development (before they arrive in the gonads), when such
      cells are very low in number, are moving along different tissues toward the
      gonadal ridges, and are not identifiable by morphological criteria alone. We
      report here that the use of PGC-specific TG-1 antibody in combination with
      immunoaffinity adhesion to plastic plates coated with anti-mouse IgM secondary
      antibody allows the isolation of reasonably pure yields of migratory PGCs from
      9.5- to 11.5-dpc mouse embryos.

PMID- 7813629
TI  - Appearance of rereplication and activation of DNA replication by calyculin A in a
      cell-free extract of activated Xenopus eggs.
AB  - When sperm nuclei were added to Xenopus S phase (activated) egg extracts
      pretreated with a serine/threonine protein phosphatase inhibitor, calyculin A, a
      density substitution experiment showed that newly synthesized sperm DNA migrated
      in two peaks, heavy-light DNA and heavy-heavy DNA, only in the presence of
      calyculin A and that the total DNA replication activity was activated. In
      contrast, the addition of calyculin A to S phase extracts about 30 min after
      addition of sperm nuclei had no effect on DNA replication activity. Calyculin A
      clearly prevented the decline of Replication Licensing Factor activity during S
      phase. These results imply that the occurrence of some rereplication and the
      activation of DNA replication by calyculin A in activated extracts may be due to
      the inhibition of inactivation of licensed sites of initiation or the increase in
      the number of the initiation sites of DNA replication because of lack of the fall
      in Licensing Factor activity during S phase.

PMID- 7813630
TI  - Cellular fibronectin expression is down-regulated at the mRNA level in
      differentiating human intestinal epithelial cells.
AB  - The expression of human cellular fibronectin (HFN) was analyzed in relation to
      the differentiation process of the human enterocyte-like cell line Caco-2. A
      single approximately 290-kDa form of HFN, corresponding to a 10.0-kb mRNA
      species, was observed in Caco-2 cells. The expression levels of both protein and
      mRNA were found to decrease to undetectable levels concomitantly to the
      differentiation process of these cells. This decline in HFN expression was
      correlated with the expression of sucrase-isomaltase (a specific marker of
      intestinal cell differentiation). These results indicate that intestinal
      epithelial expression of HFN is down-regulated through its mRNA levels and is
      correlated with the acquisition of the differentiated enterocytic phenotype.

PMID- 7813631
TI  - The influence of type I collagen on the development and maintenance of the
      osteoblast phenotype in primary and passaged rat calvarial osteoblasts:
      modification of expression of genes supporting cell growth, adhesion, and
      extracellular matrix mineralization.
AB  - Osteoblasts derived from Day 21 fetal rat calvaria grown on films of collagen
      type I exhibit an earlier and enhanced expression of the differentiated
      phenotype, compared to cells cultured on plastic. The temporal expression of
      genes characterizing three distinct periods of growth and differentiation are
      dramatically modified. During the initial proliferation period, expression of
      genes normally expressed at high levels on plastic (fibronectin, beta 1 integrin,
      and actin) was decreased from 50 to 70% in cells grown on collagen. Genes
      normally expressed at maximal levels in the postproliferative period
      (osteonectin, osteocalcin, and osteopontin) were up-regulated severalfold very
      early. Alkaline phosphatase enzyme activity was elevated 2- to 3-fold during the
      proliferation period, while mRNA levels remained low, suggesting post
      transcriptional modifications. The most dramatic consequence of culture of cells
      on collagen is the accelerated and uniform mineralization of the matrix in
      contrast to the focal mineralization confined to bone nodules in cultures on
      plastic. Type I collagen supports maintenance of osteoblast phenotypic properties
      of passaged cells in the absence of glucocorticoid supplementation required for
      differentiation of osteoblasts subcultivated on plastic. Treatment of
      proliferating rat osteoblasts on plastic with 1,25(OH)2D3 blocks osteoblast
      differentiation and matrix mineralization. Although differentiation-related genes
      (alkaline phosphatase and osteocalcin) were up-regulated by vitamin D, culture on
      the collagen matrix could not overcome the inhibition of mineralization. Taken
      together, these studies define the critical role of type I collagen in mediating
      the signaling cascade for expression of a mature osteoblast phenotype and
      mineralization of the extracellular matrix in a physiological manner.

PMID- 7813632
TI  - The coupling of pertussis toxin-sensitive G proteins to phospholipase A2 and
      adenylyl cyclase in CHO cells expressing bovine rhodopsin.
AB  - The regulation of phospholipase A2 by G protein-coupled receptors is examined in
      CHO cells which normally express the purinergic receptor and have been
      transfected with bovine rhodopsin. The purinergic receptor has been reported to
      activate both phospholipase C and phospholipase A2 in this cell line. In
      contrast, bovine rhodopsin by itself is not able to activate phospholipase A2.
      However, the photoreceptor does potentiate purinergic receptor-mediated
      phospholipase A2 activation in a light-dependent manner. Both the purinergic
      receptor stimulation of phospholipase A2 and the enhanced activity mediated by
      rhodopsin are completely pertussis toxin-sensitive, suggesting the regulation of
      phospholipase A2 by a member of the Gi family of G proteins. Both of these
      receptors also inhibit adenylyl cyclase activity. Rhodopsin-mediated inhibition
      of adenylyl cyclase is pertussis toxin-sensitive, whereas inhibition by the
      purinergic receptor is calcium-sensitive but not pertussis toxin-sensitive. These
      results suggest (1) that rhodopsin is similar to other receptors that normally
      couple to Gi when expressed in cultured cells and (2) that regulation of adenylyl
      cyclase and PLA2 in CHO cells by rhodopsin and the purinergic receptor occur via
      distinct pathways.

PMID- 7813633
TI  - Lysophosphatidic acid induction of transforming growth factors alpha and beta:
      modulation of proliferation and differentiation in cultured human keratinocytes
      and mouse skin.
AB  - Lysophosphatidic acid (LPA) is a biologically active phospholipid known to have
      growth factor-like activity on fibroblasts. Although the intracellular signal
      transduction pathways affected by LPA have been well characterized, the
      possibility that peptide growth factors are involved in the proliferative
      response of cells to LPA has not been thoroughly investigated. The focus of this
      work was to determine the effects of LPA on the proliferation and differentiation
      of early passage cultured human keratinocytes with emphasis on determining if
      transforming growth factors (TGF), types alpha and beta, are induced by LPA. The
      effects of LPA are compared with all-trans-retinoic acid (RA), a structurally
      unrelated lipid that has previously been shown to induce both TGF alpha and TGF
      beta and have pronounced effects on keratinocyte proliferation and
      differentiation. Treatment of cultured human keratinocytes with LPA or RA induced
      the production of TGF alpha by four- to eightfold. A number of structurally
      related phospholipids did not mimic the TGF alpha-inducing activity of LPA. LPA
      is mitogenic for keratinocytes and its stimulatory effect could be blocked with
      an inhibitory antibody to the EGF/TGF alpha receptor, suggesting that the
      induction of TGF alpha mediates LPA stimulation of keratinocyte proliferation.
      LPA and RA also induced both the active and latent forms TGF beta from cultured
      keratinocytes. Induction of TGF beta may mediate the effects LPA had on
      keratinocyte differentiation which were apparent by inhibition of proliferation
      (confluent cultures) and increased involucrin synthesis. Dramatic morphological
      changes were also observed after LPA treatment. Mechanistic studies suggest that
      LPA activates both pertussis toxin-sensitive and -insensitive signaling pathways
      involving protein kinase C activation and protein tyrosine phosphorylation. The
      effects of LPA on TGF alpha and TGF beta production by keratinocytes likely have
      in vivo relevance as concluded from rodent studies involving topical LPA
      treatments.

PMID- 7813634
TI  - Subcellular details of early events of differentiation induced by retinoic acid
      in human neuroblastoma cells detected by atomic force microscope.
AB  - Atomic force microscopy (AFM) is gaining ever-increasing attention in biology as
      it allows us to achieve very high resolution both in air and in liquid. Recently,
      this technique has been employed for the observation of dynamic phenomena of
      cells in their culture medium. We employed this technology for comparing
      different morphologies, neuronal and substrate-adherent type, of cell lines of
      human neuroblastoma, a tumor derived from neuroectodermal tissue. The AFM image
      allows to confirm and enrich the information given by optical microscopes adding
      further details especially on the neural protrusions. Furthermore, we took
      advantage of the possibility to perform the observation of the cells in their
      culture medium for studying the neuroblastoma cell differentiation. For the first
      time, we detected the very early events of the outgrowth of neurite-like
      structures induced by retinoic acid. A time-course experiment has showed that the
      acid induces changes in the cellular membrane and dramatic modifications in the
      cytoskeleton already within 2 h.

PMID- 7813635
TI  - Immunolocalization of thimet oligopeptidase in chicken embryonic fibroblasts.
AB  - An antiserum was raised against chicken thimet oligopeptidase (TOP), and specific
      antibodies were isolated by immunoadsorption. The specificity of the antibodies
      was confirmed by immunoblot analysis with the cell extract of cultured chicken
      fibroblasts. Subcellular localization of TOP in normal and Rous sarcoma virus
      transformed chicken embryonic fibroblasts was investigated by indirect
      immunofluorescence staining with affinity-purified, monospecific anti-TOP
      antibodies. In addition to the diffuse reaction expected for a cytosolic enzyme,
      a punctate, cytoplasmic localization was observed. The appearance of the
      organelles containing TOP did not correspond to that expected for secondary
      lysosomes, mitochondria, endoplasmic reticulum, or Golgi apparatus, but did
      resemble that of endosomes. When cells were allowed to internalize Lucifer yellow
      before fixation, some of the organelles containing TOP were observed to contain
      Lucifer yellow. Moreover, those organelles containing TOP were positively
      immunolabeled with the anti-transferrin receptor antibody. We conclude that part
      of the TOP in chicken embryonic fibroblasts is located in endosomes and discuss
      the implications of this.

PMID- 7813636
TI  - Ornithine decarboxylase and S-adenosylmethionine decarboxylase expression during
      the cell cycle of Chinese hamster ovary cells.
AB  - Cells in mitosis were harvested from exponentially growing Chinese hamster ovary
      cells by the mitotic detachment technique. Immediately after harvesting, the
      mitotic cells were seeded in tissue culture flasks and incubated at 37 degrees C
      in a CO2 incubator. Care was taken not to perturb the progression of cells
      through the cell cycle. At every hour after seeding for 14 h, cells were
      collected for analysis of cell cycle distribution, cellular polyamine content,
      ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AdoMetDC)
      activities, and relative mRNA contents. The progression through the cell cycle
      was monitored by DNA flow cytometry. The putrescine, spermidine, and spermine
      levels were approximately doubled during the cell cycle: putrescine mainly during
      late S and G2, spermidine continuously during the entire cell cycle, and spermine
      mainly during G1 and S. The ODC activity was low in seeded mitotic cells and the
      enzyme was activated in late G1 and reached a plateau in S phase. A second burst
      in activity was observed during late S phase and maximal ODC activity was found
      at the S/G2 transition. The relative ODC mRNA level approximately doubled during
      the cell cycle and the increase in the relative level mainly took part during mid
      and late S phase. AdoMetDC activity increased in late G1 and a first maximum was
      observed during the G1/S transition. A second burst in activity was found in mid
      S phase. Maximal AdoMetDC activity was found in G2. The relative AdoMetDC mRNA
      approximately doubled during the cell cycle and the increase in the relative
      level mainly took place during late G1 and early S phase. Our results indicate
      that polyamine synthesis was regulated at transcriptional and translational/post
      translational levels during the cell cycle of Chinese hamster ovary cells.

PMID- 7813637
TI  - PC12 variants with altered ornithine decarboxylase expression patterns exhibit
      altered signal transduction capabilities.
AB  - Nerve growth factor (NGF) induced differentiation of primary and permanent
      neuronal cell cultures is accompanied by a rapid and transient induction of
      ornithine decarboxylase (ODC) mRNA and enzymatic activity; a similar ODC
      induction accompanies mitogenic effectors in many additional cell types. In an
      effort to assess the role of ODC activity in neuronal cell biology, we have used
      the ODC suicide substrate inhibitor difluoromethylornithine (DFMO) to select PC12
      cell variants with altered ODC expression patterns and characterized the
      resulting phenotypes. The variants fall into three distinct classes based upon
      their patterns of ODC mRNA and ODC activity levels; however, all are severely
      compromised in their ability to respond properly to NGF treatment. Following NGF
      treatment, none of the variants exhibits any morphological differentiation. In
      addition, none of the variants is capable of properly inducing either c-fos mRNA
      (an "immediate early" response) or GAP-43 mRNA (a "late" response) following NGF
      treatment. Our data suggest that altered ODC metabolism can lead to inactivation
      of element(s) active very early in the normal NGF signal transduction cascade.

PMID- 7813638
TI  - New observations on input to spino-cervical tract neurons from muscle afferents.
AB  - Peripheral input to spino-cervical tract (SCT) neurons located in the L4 and L5
      segments of the cat spinal cord was investigated using both extracellular and
      intracellular recording. The main aim was to find out whether midlumbar SCT
      neurons are excited monosynaptically not only by cutaneous afferents but also by
      group II muscle afferents, as in the sacral segments but apparently not in the
      caudal lumbar segments. Input from group II muscle afferents was found in 73% of
      investigated neurons; the latencies of excitation by group II afferents were
      compatible with a monosynaptic coupling between these afferents and 62% of
      neurons. The majority of the midlumbar SCT neurons were excited by group II
      afferents of the quadriceps and deep peroneal nerves. The predominant
      monosynaptic input from cutaneous afferents to the same neurons was from the
      saphenous nerve.

PMID- 7813639
TI  - Perception of vibrotactile stimuli during motor activity in human subjects.
AB  - Previous studies have shown that voluntary motor activity decreases the ability
      to detect near-threshold electrical stimuli applied to the skin, but has no
      effect on the perception of either suprathreshold electrical stimuli or natural
      thermal stimuli (warmth, heat pain). The present study was undertaken to
      determine if the perception of natural tactile stimuli (vibrotactile) is
      diminished by motor activity (rhythmical isometric flexions and extensions about
      the elbow). The stimuli were applied at three different sites on the operant arm-
      ventral forearm, thenar eminence and distal digit--to examine also the influence
      of the proximity of the stimulated site to the active muscles on perception. The
      ability to detect near-threshold stimuli at the two more proximal stimulation
      sites was significantly reduced during the motor task, and these effects were
      more pronounced and widespread with higher levels of target force (20 N vs 50 N).
      Discrimination of small differences in the intensity of suprathreshold stimuli,
      at all three sites, was unchanged during the motor task. Finally, the subjective
      intensity of suprathreshold vibrotactile stimuli was reduced, in a nonlinear
      fashion, during the motor task; proximity again influenced the degree of
      modulation. In contrast a previous study showed no change in magnitude estimates
      of suprathreshold electrical stimuli during isotonic flexion and extension. Some
      possible reasons for the discrepancy are discussed. In addition, our previous
      suggestion that movement produces a simple reduction in the signal-to-noise ratio
      (i.e. the gating signal modelled as a masking stimulus) cannot explain the
      present results, so more complex models are required.

PMID- 7813640
TI  - Cortical motor representation of the ipsilateral hand and arm.
AB  - We sought to determine whether motor evoked potentials (MEPs) as well as silent
      periods could be produced in hand and shoulder muscles by transcranial magnetic
      stimulation (TMS) of the ipsilateral cerebral hemisphere and, if so, whether
      their cortical representations could be mapped with respect to those of
      contralateral muscles. In six normal subjects, we delivered ten stimuli each to a
      grid of sites 1 cm apart on the scalp. The EMG was recorded and averaged from the
      contralateral first dorsal interosseous (FDI) and risorius (facial) muscles at
      rest and the ipsilateral FDI muscle, which was voluntarily contracted. In four of
      these subjects and an additional subject, we used the same mapping technique and
      recorded from the deltoid muscle on the right and left sides and the
      contralateral FDI during activation of the ipsilateral deltoid. In all subjects,
      the cortical representation of the contralateral risorius was anterolateral to
      that of the FDI. The contralateral deltoid could be activated in only three
      subjects. In them, its representation was slightly medial to that of the FDI. All
      subjects had at least one scalp site where TMS produced MEPs in the ipsilateral
      FDI. Two subjects had rich ipsilateral hand representations with multiple
      ipsilateral MEP sites. Both had ipsilateral MEP sites near the representation of
      the contralateral FDI, but the largest ipsilateral MEPs occurred with TMS at more
      lateral sites, which were near the representation of the contralateral risorius.
      In these subjects, the ipsilateral deltoid was preferentially activated at sites
      medial and posterior to those activating the contralateral muscle. Ipsilateral
      TMS also produced silent periods in the FDI in all subjects. These silent periods
      were much more frequent than the ipsilateral MEPs and tended to occur with TMS
      near the representation of the contralateral FDI. The excitatory cortical
      representation of the ipsilateral arm muscles is accessible to TMS in normal
      subjects and is different from that of the homologous contralateral muscles. The
      hand may have two ipsilateral representations, one of which produces silent
      periods and the other MEPs at the same stimulus intensity.

PMID- 7813642
TI  - Fitts' law in two-dimensional task space.
AB  - A traditional continuous Fitts' task may be described as a one-dimensional
      oscillation between two targets. The combination of two such oscillations along
      intersecting axes gives rise to a two-dimensional aiming task, allowing the study
      of the speed-accuracy trade-off in two-dimensional task space. In two experiments
      subjects were asked to draw as many ellipses as possible while passing through
      four targets, arranged around the extreme points of the two major axes of a model
      ellipse. In the first experiment, task difficulty was manipulated simultaneously
      along the two axes of the ellipse. Regardless of ellipse eccentricity and
      orientation, movement time (MT) was found to depend linearly on Fitts' index of
      difficulty (ID), which combines between-target distance and target width. In the
      second experiment, ID was manipulated independently for the short and the long
      axes of the ellipse. There was a strong linear relation between MT and ID
      averaged over the two axes, with the two independent measures of task difficulty
      exerting interactive effects on MT: the higher the ID on one axis, the smaller
      the effect of the ID on the other. The present results demonstrate that Fitts'
      law, only examinated so far in one-dimensional aiming tasks, generalises to two
      dimensional task space.

PMID- 7813641
TI  - The metabolic brain pattern of young subjects given scopolamine.
AB  - The effect of an intravenous dose of 0.5 mg of scopolamine on the functional
      brain activity of normal subjects performing auditory discrimination (CPT) was
      determined in two independent positron emission tomography studies with [18F] 2
      fluoro-deoxyglucose. In the first preliminary study, the most significant effect
      found was a reduction in the functional activity of the thalamus. In the second
      "hypothesis-testing" study, an equally prominent effect on thalamic functional
      activity was seen. Because the second study was performed on a high-resolution
      scanner with improved methodology, we re-examined scopolamine's effects on those
      brain regions established as determinants of CPT. Of the regions affected, the
      reduction in cingulate and the increase in basal ganglia metabolic rates were the
      most notable. We concluded that scopolamine's effects on the functions of
      thalamic, cingulate and basal ganglia are the likely causes of scopolamine's well
      described attention-altering properties. Alterations in these same brain
      structures could be responsible for scopolamine's effects on other cognitive
      functions, e.g., memory. Alternatively, scopolamine's effects on other brain
      structures such as the hippocampus and frontal cortex could underlie
      scopolamine's effects on these other cognitive functions. Studies of
      scopolamine's regional metabolic effects in subjects performing these other
      cognitive tasks at more than a single dose and at more than one post-drug time
      are needed to discriminate between these two possibilities.

PMID- 7813643
TI  - Two mechanisms underlying the induction of long-term potentiation in motor cortex
      of adult cat in vitro.
AB  - Long-term potentiation of synaptic transmission (LTP), as documented by the
      enhancement of evoked field potentials in layer III following stimulation of the
      underlying white matter, has been studied in slices of motor cortex from adult
      cats. With a 1 M NaCl-filled recording electrode, LTP was induced only in one out
      of eight slices. When the recording electrode in addition contained 5 mM
      bicuculline metiodide, LTP was obtained with a much higher rate of success
      (15/19), suggesting that reduction of GABAA receptor-mediated inhibition
      facilitated the induction of LTP in the motor cortex. Bath application of DL-2
      amino-5-phosphonovaleric acid (APV, 100 microM) or Ni2+ (100 microM)
      significantly reduced the success rate for LTP occurrence (6/16 and 5/16,
      respectively); but when LTP was induced, it did not show significant change in
      magnitude and time course. In slices perfused with APV (100 microM) plus Ni2+
      (100 microM), LTP induction was completely blocked (0/12). These results suggest
      that two different mechanisms may subserve LTP induction in the cat motor cortex:
      one is mediated by N-methyl-D-aspartate receptors and can be blocked by APV; the
      other may be mediated by low-threshold calcium channels and can be blocked by
      Ni2+.

PMID- 7813644
TI  - Long-lasting potentiation and depression by novel isoproterenol and
      cholecystokinin 8-S interactions in the dentate gyrus.
AB  - In the in vitro hippocampal slice, novel interactions of a beta-adrenergic
      agonist (l-isoproterenol) and neuropeptide (cholecystokinin 8-S) differentially
      produce long-lasting modifications in the dentate gyrus. When co-applied, a low
      concentration of l-isoproterenol (50-75 nM) and cholecystokinin 8-S (1.0 microM)
      produce long-lasting depression of evoked action potentials (i.e., population
      spikes). In contrast, the same concentration of l-isoproterenol followed by a 30
      min wash with artificial cerebrospinal fluid and application of cholecystokinin 8
      S produces long-lasting potentiation of evoked action potentials. In neither
      condition are there corresponding modifications of excitatory post-synaptic
      potentials. These results indicate that l-isoproterenol and cholecystokinin 8-S
      temporally interact to differentially produce depression or potentiation of
      granule cell-activation In contrast to long-lasting modifications produced by
      continuous application of 1.0 microM l-iso-proterenol, in which both evoked
      action potentials and excitatory post-synaptic potentials are affected, the
      present novel paradigm may modify an extra-synaptic locus.

PMID- 7813645
TI  - Spatial selectivity of go/no-go neurons in monkey prefrontal cortex.
AB  - We examined single-unit activity in the inferior prefrontal cortex during a
      visual go/no-go discrimination task under maintained visual fixation. The monkeys
      had to base their response on either the color, shape, or position of a
      discriminative cue, and the relevant task condition was indicated by the color of
      the fixation spot. We analyzed the spatial selectivity of 128 go/no-go neurons
      showing a marked differential cue-period activity that depended on whether the
      stimulus signaled a go or no-go response. Most of these neurons (n = 106, 83%)
      showed asymmetry between their responses to stimuli in the contralateral and
      ipsilateral visual fields. Seventy-seven of these neurons had a contralateral
      preferential field, and 29 had an ipsilateral preferential field. These results
      show that in many inferior prefrontal neurons a degree of differentiation in
      their responses to go and no-go stimuli depends on the cue positions, and that
      the coding of behavioral meaning is carried out mainly in the contralateral
      hemisphere.

PMID- 7813646
TI  - Sensorimotor transformation in a spinal motor system.
AB  - To use sensory information from the skin to guide motor behaviour the central
      nervous system must transform sensory coordinates into movement coordinates. As
      yet, the basic principles of this crucial neural computation are unclear. One
      motor system suitable as a model for the study of such transformations is the
      spinal withdrawal reflex system. The spatial organization of the cutaneous input
      to these reflexes has been characterized, and we now introduce a novel method of
      motion analysis permitting a quantitative analysis of the spatial input-output
      relationship in this motor system. For each muscle studied, a "mirror-image"
      relationship was found between the spatial distribution of reflex gain for
      cutaneous input and the pattern of cutaneous unloading ensuing on contraction.
      Thus, there is an "imprint" of the movement pattern on this motor system
      permitting effective sensorimotor transformation. This imprint may indicate the
      presence of a learning process which utilizes the sensory feedback ensuing on
      muscle contraction.

PMID- 7813647
TI  - Masked long-term potentiation in kitten visual cortex in vitro.
AB  - In slices from the visual cortex of kittens maintained in vitro, long-term
      potentiation of synaptic transmission following high frequency stimuli (10 Hz, 2
      min) delivered at low to medium stimulus intensities (80 to 200 microA), is
      accompanied by changes of certain electrophysiological measures recorded
      intracellularly, such as long-lasting depolarization of membrane potential and
      decreased threshold to elicitation of an action potential. These parameters have
      never before been shown to be altered following high frequency stimulation in
      other systems widely used in studying synaptic plasticity, such as in hippocampal
      neurons. Another important difference between results from these two systems is
      that the amplitude of the excitatory post-synaptic potential is enhanced after
      high frequency stimulation in hippocampal neurons, whereas in striate cortex from
      young kittens, we observed a decrease. We demonstrate here that this decrease can
      be reversed to show enhancement from the original amplitude, upon clamp of
      membrane potential back to the voltage observed prior to stimulation. Thus, what
      appears to be "long-term depression" of synaptic transmission, as recorded
      extracellularly and represented by diminished flow of synaptic current, can be
      reversed by stepping membrane voltage back to the pre-high frequency stimulation
      level, to produce responses that then become consistent with long-term
      potentiation.

PMID- 7813648
TI  - Activation of mechanonociceptors by pro-inflammatory peptides melittin and PLAP
      peptide.
AB  - Studies were conducted to characterize the chemical reactivity of A and C fiber
      mechanical and mechanoheat nociceptors that innervate the goat palatal mucosa. In
      mechanical nociceptors, no significant chemical reactivity to either serotonin,
      bradykinin, prostaglandin E1, or prostaglandin E2 was observed, regardless of
      whether substances were injected singly or in spaced sequential combinations.
      Weak reactivity was observed in mechanoheat nociceptors. In contrast, both
      mechanical and mechanoheat nociceptors were activated by novel proinflammatory
      peptides. Nineteen of 30 mechanonociceptors and 12 of 13 mechanoheat nociceptors
      were activated by the insect venom peptide, melittin or its endogenous mammalian
      homologue PLAP (phospholipase A2 activating protein) peptide. Low threshold
      mechanoreceptors were never activated by melittin or PLAP peptide.

PMID- 7813649
TI  - Input to the primate frontal eye field from the substantia nigra, superior
      colliculus, and dentate nucleus demonstrated by transneuronal transport.
AB  - The purpose of these experiments was to study the subcortical input to the
      frontal eye field (FEF) and to determine which subcortical structures might
      project to the FEF via pathways that contain only a single intervening synapse.
      We used retrograde transneuronal transport of herpes simplex virus type 1 (HSV-1)
      to label second-order neurons that send information to the FEF of cebus monkeys.
      The saccade region of the FEF was identified physiologically using intracortical
      stimulation and then injected with a strain of HSV-1 known to be transported
      transneuronally in the retrograde direction. Retrograde transport of virus
      labeled neurons was observed in all the thalamic sites known to innervate the
      FEF. In addition, we found neurons labeled by transneuronal transport in three
      subcortical sites: the pars reticulata of the substantia nigra, the optic and
      intermediate gray layers of the superior colliculus, and a posterior portion of
      the dentate nucleus of the cerebellum. Each of these sites has been shown in
      prior studies to project to thalamic regions that innervate the FEF. Moreover,
      the neurons labeled through transneuronal transport were located in a subregion
      of each subcortical site that is known to be involved in oculomotor control.
      These observations demonstrate that signals from the substantia nigra, superior
      colliculus and dentate nucleus can have a significant influence on the output of
      the FEF.

PMID- 7813650
TI  - Neuronal activity in nucleus ambiguous during deglutition and vocalization in
      conscious monkeys.
AB  - Extracellular recordings were made from the nucleus ambiguous in three conscious
      Macaca nemestrina monkeys during spontaneous vocalizations and swallows. The
      temporal relationship of neuronal activity to swallowing was inferred through
      correlation with the thyroarytenoid electromyographic (EMG) activity.
      Videofluoroscopic analysis of a fourth monkey during swallows of barium
      impregnated fruit juice established the temporal relationship between swallowing
      and thyroarytenoid EMG activity. Of 691 cells recorded from the nucleus ambiguous
      and its adjacent area, the neuronal activity of 80 cells showed modulation during
      swallowing. Sixty-two cells were classified as "active" cells, with increased
      activity in relation to swallowing, while 18 cells were classified as
      "suppressed" cells, with tonic activity that reduced with swallowing. A continuum
      of latency was seen between the onset of modulation of these cells and the onset
      of swallowing, from "early" before the swallow to "late" after the swallow onset
      with most of the cells (44 cells) showing modulation near the onset of the
      swallow. A majority (37) of the 62 active swallowing-related cells also
      discharged with vocalization, but they demonstrated a lower discharge frequency
      and a longer burst duration during swallowing. Of the 18 suppressed swallowing
      related cells, 11 cells discharged phasically with the respiratory cycle and may
      be a part of the ventral medullary respiratory center. This chronic awake primate
      model would preserve the many sensory inputs that may modify the oropharyngeal
      swallow and may better approximate human physiology.

PMID- 7813652
TI  - Is abnormal retinal development in albinism only a mammalian problem? Normality
      of a hypopigmented avian retina.
AB  - The central retina in hypopigmented mammals is underdeveloped. In the outer
      retina this deficit is confined to rods. Also, many ganglion cells in temporal
      regions project inappropriately to the contralateral hemisphere. This study
      addresses the question of whether pigment-related abnormalities occur in the
      central retina of a non-mammal, the bird. Birds have a highly developed central
      retina, but unlike most mammals they do not have a significant uncrossed retinal
      projection. Consequently, examination of the retinae of hypopigmented birds will
      reveal whether there is a relationship between the two abnormalities. Also if one
      of the primary effects of albinism is centred on rods, then albino birds may not
      show a deficit, because their retinae are cone dominated. Retinae from normally
      pigmented and two forms of hypopigmented budgerigars (Melopsittacus undulatus)
      were studied. Measurements of layer thickness, cell density and cell size were
      made at a range of locations in the ganglion cell layer and in the inner and the
      outer nuclear layers. Estimates of cone numbers were also made. Each strain of
      bird had an area of increased retinal layer thickness in dorso-temporal regions,
      but not a fovea. Although there were variations in the measurements undertaken
      between the strains, none were pigment related or consistent with the abnormality
      found in the central retina in albino mammals. Consequently, the underdevelopment
      of the central retina seen in hypopigmented mammals does not occur in this bird.
      There are two possible explanations for this result. First, normal mammalian
      retinal development may depend partly on time-dependent interactions in the
      maturation of the retinal pigment epithelium and the neural retina. Although
      there is a common time table for the development of the mammalian visual system
      when expressed in terms of the caecal period, which is between conception and eye
      opening, the pace of retinal development in birds is accelerated, which may alter
      interactions between these regions. Second, as the bird retina is cone dominated,
      any deficits in albino strains may be relatively minor.

PMID- 7813651
TI  - Reduction of GABAA receptor binding of [3H]muscimol in the barrel field of mice
      after peripheral denervation: transient and long-lasting effects.
AB  - The effect of peripheral sensory deprivation upon GABAA receptor binding of
      [3H]muscimol was investigated in the barrel cortex--cortical representation of
      mystacial vibrissae of mice--by means of in vitro quantitative autoradiography.
      Unilateral lesions of all vibrissae or selected rows of whiskers were performed
      neonatally or in adulthood. [3H]muscimol binding was examined after various
      survival times up to 60 days. Both types of lesions performed in adult mice
      resulted in a transient decrease (10-25%) of binding values in the deafferented
      areas of the barrel field as compared with the unoperated control side. Sixty
      days after denervation [3H]muscimol binding returned to control values. Similar
      results were found after neonatal removal of all vibrissae. Neonatal lesion of
      selected rows of vibrissae, however, resulted in a decrease of [3H]muscimol
      binding (by about 26%) lasting up to 60 days in corresponding rows of barrels.
      This last result was accompanied by severe cytoarchitectonic malformation of the
      barrel field. The results support the hypothesis that a decrease of inhibition
      plays a facilitatory role in the plastic reorganization of cortical circuitry.

PMID- 7813653
TI  - The responses of secondary endings of cat soleus muscle spindles to succinyl
      choline.
AB  - This report describes the effects of succinylcholine (SCh) on the secondary
      endings of cat soleus muscle spindles and attempts to explain them in terms of
      the action of the drug on intrafusal fibres. All but 2 of 41 secondary endings
      studied in detail showed a significant response to a single intravenous injection
      of 200 micrograms kg-1 SCh. This consisted of a rise in the resting rate or
      development of a resting discharge if the spindle had previously been silent and
      an increase in the response to stretch. The increases in the responses to stretch
      were weaker than those observed for primary endings of spindles, but were much
      larger than those of tendon organs, which showed very little effect with this
      concentration of drug. The response to SCh showed two features consistent with
      its action being mediated via an intrafusal muscle fibre contraction rather than
      a direct depolarising action on the afferent nerve ending. In the presence of
      SCh, secondary endings were able to maintain a discharge during muscle shortening
      at rates, on average, more than 5 times greater than under control conditions.
      Secondly, the increase in spindle discharge produced by SCh showed a length
      dependence similar to that for fusimotor stimulation. Further support for the
      action of SCh being principally via an intrafusal fibre contraction was provided
      by the observation that its effects were abolished by the neuromuscular blocker
      gallamine triethiodide.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7813654
TI  - Rat posterior parietal cortex: topography of corticocortical and thalamic
      connections.
AB  - Anatomical and functional findings support the contention that there is a
      distinct posterior parietal cortical area (PPC) in the rat, situated between the
      rostrally adjacent hindlimb sensorimotor area and the caudally adjacent secondary
      visual areas. The PPC is distinguished from these areas by receiving thalamic
      afferents from the lateral dorsal (LD), lateral posterior (LP), and posterior
      (Po) nuclei, in the absence of input from the ventrobasal complex (VB) or dorsal
      lateral geniculate (DLG) nuclei. Behavioral studies have demonstrated that PPC is
      involved in spatial orientation and directed attention. In the present study we
      used fluorescent retrograde axonal tracers primarily to investigate the cortical
      connections of PPC, in order to determine the organization of the circuitry by
      which PPC is likely to participate in these functions, and also to determine how
      the topography of its thalamic connections differs from that of neighboring
      cortical areas. The cortical connections of PPC involve the ventrolateral (VLO)
      and medial (MO) orbital areas, medial agranular cortex (area Fr2), portions of
      somatic sensory areas Par1 and Par2, secondary visual areas Oc2M and Oc2L,
      auditory area Te1, and retrosplenial cortex. The secondary visual areas Oc2L and
      Oc2M have cortical connections which are similar to those of PPC, but are
      restricted within orbital cortex to area VLO, and within area Fr2 to its caudal
      portion, and do not involve auditory area Te1. The cortical connections of
      hindlimb cortex are largely restricted to somatic sensory and motor areas.
      Retrosplenial cortex, which is medially adjacent to PPC, has cortical connections
      that are prominent with visual cortex, do not involve somatic sensory or auditory
      cortex, and include the presubiculum. We conclude that PPC is distinguished by
      its pattern of cortical connections with the somatic sensory, auditory and visual
      areas, and with areas Fr2, and VLO/MO, in addition to its exclusive thalamic
      connectivity with LD, LP and Po. Because recent behavioral studies indicate that
      PPC, Fr2 and VLO are involved in directed attention and spatial learning, we
      suggest that the interconnections among these three cortical areas represent a
      major component of the circuitry for these functions in rats.

PMID- 7813655
TI  - Ascending projections of posterior canal-activated excitatory and inhibitory
      secondary vestibular neurons to the mesodiencephalon in cats.
AB  - The axonal projections of 62 posterior canal (PC)-activated excitatory and
      inhibitory secondary vestibular neurons were studied electrophysiologically in
      cats. PC-related neurons were identified by monosynaptic activation elicited by
      electrical stimulation of the vestibular nerve and activation following nose-up
      rotation of the animal's head. Single excitatory and inhibitory neurons were
      identified by antidromic activation following electrical stimulation of the
      contralateral and ipsilateral medial longitudinal fasciculus, respectively. The
      oculomotor projections of identified neurons were confirmed with a spike
      triggered averaging technique. The axonal projections of the identified neurons
      were then studied by systematic, antidromic stimulation of the mesodiencephalon.
      Excitatory neurons showed two main types of axonal projections. In one type,
      axonal branches were issued to the interstitial nucleus of Cajal, central gray,
      and thalamus including the ventral posterolateral, ventral posteromedial, ventral
      lateral, ventral medial, centromedian, central lateral, lateral posterior, and
      ventral lateral geniculate nuclei. The other type was more frequently observed,
      giving off axon collaterals to the above-mentioned regions and to Forel's field H
      as well. Inhibitory neurons issued axonal branches to limited areas which
      included the central gray, interstitial nucleus of Cajal, its adjacent reticular
      formation and caudalmost part of Forel's field H, but not the rostral part of the
      Forel's field H and the thalamus. These results suggest that PC-related
      excitatory neurons participate in the genesis of vertical eye movements and in
      the perception of the vestibular sensation, and that PC-related inhibitory
      neurons seem to take part only in the genesis of vertical eye movements.

PMID- 7813656
TI  - Spontaneous recognition of object configurations in rats: effects of fornix
      lesions.
AB  - The effects of fornix lesions were examined in an object recognition memory test
      based on spontaneous exploration. In the standard condition an object (A) was
      presented in the sample phase and then presented again in the test phase
      alongside a new object (B). Both fornix-transected (Fx) and control (Co) rats
      spent more time exploring the new object than the familiar object after retention
      delays of 1 min and 15 min. In two configural conditions designed to test
      sensitivity to reconfigured stimuli, the original sample (A) was now either re
      presented alongside its rearranged version ([symbol: see text]) or, the re
      arranged version itself ([symbol: see text]) was presented with a new object (B).
      In the first configural condition, both the Co and Fx rats spent more time
      exploring the reconfigured sample ([symbol: see text]) than the original version
      of the sample (A) following a delay of 1 min, but not 15 min. In the second
      configural condition, both Co and Fx rats spent more time exploring the new
      object (B) than the reconfigured version of the sample ([symbol: see text])
      following a delay of 15 min but not 1 min. These present results do not support
      Sutherland and Rudy's hypothesis on hippocampal function; however, they
      demonstrate that memory of objects as well as memory of reconfigured objects
      could easily be examined in a test based on spontaneous exploratory behaviour.

PMID- 7813657
TI  - Vestibular and somatosensory contributions to responses to head and body
      displacements in stance.
AB  - The relative contribution of vestibular and somatosensory information to
      triggering postural responses to external body displacements may depend on the
      task and on the availability of sensory information in each system. To separate
      the contribution of vestibular and neck mechanisms to the stabilization of
      upright stance from that of lower body somatosensory mechanisms, responses to
      displacements of the head alone were compared with responses to displacements of
      the head and body, in both healthy subjects and in patients with profound
      bilateral vestibular loss. Head displacements were induced by translating two 1
      kg weights suspended on either side of the head at the level of the mastoid bone,
      and body displacements were induced translating the support surface. Head
      displacements resulted in maximum forward and backward head accelerations similar
      to those resulting from body displacements, but were not accompanied by
      significant center of body mass, ankle, knee, or hip motions. We tested the
      effect of disrupting somatosensory information from the legs on postural
      responses to head or body displacements by sway-referencing the support surface.
      The subjects' eyes were closed during all testing to eliminate the effects of
      vision. Results showed that head displacements alone can trigger medium latency
      (48-84 ms) responses in the same leg and trunk muscles as body displacements.
      Nevertheless, it is unlikely that vestibular signals alone normally trigger
      directionally specific postural responses to support surface translations in
      standing humans because: (1) initial head accelerations resulting from body and
      head displacements were in opposite directions, but were associated with
      activation of the same leg and trunk postural muscles; (2) muscle responses to
      displacements of the head alone were only one third of the amplitude of responses
      to body displacements with equivalent maximum head accelerations; and (3)
      patients with profound bilateral vestibular loss showed patterns and latencies of
      leg and trunk muscle responses to body displacements similar to those of healthy
      subjects. Altering somatosensory information, by sway-referencing the support
      surface, increased the amplitude of ankle muscle activation to head displacements
      and reduced the amplitude of ankle muscle activation to body displacements,
      suggesting context-specific reweighting of vestibular and somatosensory inputs
      for posture. In contrast to responses to body displacements, responses to direct
      head displacements appear to depend upon a vestibulospinal trigger, since trunk
      and leg muscle responses to head displacements were absent in patients who had
      lost vestibular function as adults.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7813658
TI  - Activity of neurons in Forel's field H during orienting head movements in alert
      head-free cats.
AB  - Single unit activities were recorded in Forel's field H (FFH) at the
      mesodiencephalic junction during orienting head movements in two alert cats under
      head-free conditions. Recordings were made of 63 neurons of which 20 showed
      phasic firing that preceded the onset of head movements by 20-100 ms and was
      temporally related to the dynamic phase of the orienting head movement. Nineteen
      of these neurons showed a preference for upward movements, while the remaining
      neuron preferred downward movements. Activities during orienting movements in
      eight different directions (each separated by 45 degrees) were systematically
      analyzed for 12 of the 19 upward-preferring neurons. The activities were broadly
      tuned; in most of the neurons, maximum activity was observed for direct upward
      movements (+90 degrees), but significant activity was also observed for
      ipsilateral and contralateral oblique upward movements (+45 degrees and +135
      degrees). In these cases, the increase in activity preceded the onset of the
      movement. Some increase in activity was also observed for ipsilateral and
      contralateral horizontal, oblique downward and downward movements. However, the
      increase in activity in the latter cases occurred simultaneously with or lagged
      behind the onset of the movement and was often preceded by a decrease in
      activity. The same pattern of directional tuning was observed in the EMG of the
      biventer cervicis muscle, a target of FFH neurons. The preferred directions of
      the 12 upward-preferring neurons were estimated by calculating the vector sum of
      the activity and were distributed between +68 degrees and +108 degrees. The same
      amount of activity was observed for ipsilateral and contralateral oblique upward
      movements, suggesting that FFH neurons on both sides of the brainstem are equally
      activated even during oblique orienting. Input from the ipsilateral superior
      colliculus was investigated in 18 neurons, all of which were orthodromically
      activated with a latency of 0.8-1.8 ms, suggestive of a mono- or disynaptic
      excitatory connection. Seven neurons were identified as descending projection
      neurons by antidromic activation from the ipsilateral medullary reticular
      formation. Repetitive microstimulation of unilateral FFH induced oblique upward
      head movements and an accompanying torsional component, while simultaneous
      bilateral stimulation at comparable stimulus strength induced purely upward head
      movements. These results strongly suggest that the vertical component of
      orienting head movements is encoded by equal bilateral activation of the FFH.

PMID- 7813659
TI  - Prolonged responses in rat cerebellar Purkinje cells following activation of the
      granule cell layer: an intracellular in vitro and in vivo investigation.
AB  - We obtained intracellular recordings of 84 Purkinje cells in vitro from guinea
      pig slices and of 35 cells in vivo from ketamine-anesthetized rats in order to
      assess detailed properties of synaptic responses in Purkinje cells following
      granule cell activation. In vitro, electrical stimulation of the granule cell
      layer underlying recorded Purkinje cells was used in sagittal slices to
      predominantly activate synapses on ascending granule cell axons. In vivo,
      stimulation of the upper lip was used to activate Purkinje cells overlying the
      upper lip patch in the granule cell layer of crus IIa. In the presence of a GABAA
      antagonist, Purkinje cells at resting membrane potential responded to both
      electrical stimulation in vitro and peripheral stimulation in vivo, with a
      depolarization of 1-10 mV amplitude that lasted for 100-300 ms in the absence of
      climbing fiber input. Similar prolonged depolarizations could also be induced by
      brief depolarizing current pulses delivered through the recording electrode,
      demonstrating that either synaptic or direct depolarization may activate inward
      currents leading to a sustained response. In support of this hypothesis we found
      that prolonged depolarizations were shortened significantly when stimulation in
      the granule cell layer or intracellular current pulses were delivered during
      hyperpolarizing current steps. Stimulation in the granule cell layer or
      intracellular current pulses delivered during periods of spontaneous somatic
      spiking resulted in prolonged depolarizations in dendritic recordings, which were
      accompanied by an increase in somatic spiking frequency. Following upper lip
      stimulation in vivo, this increase in somatic spiking was interrupted by an
      inhibition of 10-50 ms duration. In a majority of recordings, this inhibition did
      not completely abolish prolonged depolarizations, however, and a delayed increase
      in somatic spike frequency was still observed. These results suggest that
      prolonged increases in Purkinje cell spike frequency following peripheral
      stimulation are due to an underlying prolonged dendritic depolarization induced
      by granule cell input. Further, a single, short burst of input via ascending
      granule cell axons appears to be sufficient to induce these responses.

PMID- 7813660
TI  - Glutamate activation of cat thalamic reticular nucleus: effects on response
      properties of ventroposterior neurons.
AB  - The thalamic reticular nucleus (RTN) exerts an inhibitory influence upon the
      dorsal thalamus. During wakefulness and arousal, RTN neurons fire tonically,
      whereas during slow-wave sleep they fire rhythmic high frequency bursts. The
      effects produced by RTN inhibition upon the activity of dorsal thalamic neurons
      will therefore vary in relation to the firing mode of the RTN neurons. In the
      present study, we compared the effects of oscillating RTN neurons and of RTN
      neurons tonically activated with glutamate on the response profiles of single
      units reacting to controlled cutaneous stimulation in cat ventroposterior lateral
      thalamic nucleus (VPL). Experiments were performed under light barbiturate
      anesthesia and prior to the glutamate activation of the RTN, both RTN and VPL
      neurons showed spontaneous bursting patterns of activity consistent with the
      oscillatory mode. Typically, a cutaneous stimulus evoked a short latency
      excitatory response in VPL followed by a period of complete inhibition termed
      post-stimulus inhibition (PSI). In many neurons, the PSI was followed by a period
      of increased activity termed post-inhibitory excitation (PIE). Ejection of
      glutamate in the identified somatosensory division of the RTN shifted the
      oscillatory firing of its neurons to a high tonic mode and usually resulted in a
      decrease in VPL neuronal activity. Significant variations were observed in the
      occurrence and the magnitude of the effects among the different components of
      neuronal activity examined. Tonic activation of the RTN resulted in a significant
      reduction of ON- and OFF-PIEs in 81% of cases (30/37) and of spontaneous activity
      in 67% (22/33). In contrast, the response to a cutaneous stimulus was decreased
      in only 29% of cases (17/59) and was significantly increased in 24% (14/59).
      Tonic activation of the RTN by glutamate resulted in little change in the firing
      pattern of VPL neurons, and both short and long spike intervals were affected in
      a similar proportion. We conclude that the components of VPL neuronal activity
      most affected by switching RTN neurons from the oscillatory to the tonic mode are
      those normally dependent upon RTN neuronal oscillation. The present results also
      suggest that lowering background activity, such as occurs during the transition
      from sleep to wakefulness, is a factor leading to increase in the responsiveness
      of dorsal thalamic neurons.

PMID- 7813661
TI  - Distribution of GABA immunoreactivity in kainic acid-treated rabbit retina.
AB  - Ischaemic retinal cell degeneration seems to involve both NMDA and non-NMDA
      receptor over-stimulation. However, different retinal cell types differ largely
      in their susceptibility to excitatory amino acid-induced neurotoxicity. We have
      investigated the vulnerability of GABAergic cells in the rabbit retina to the non
      NMDA receptor agonist kainic acid (KA). The distribution of GABA immunoreactivity
      (GABA-IR) was examined in the central inferior retina at different survival times
      (5 h-6 days) following an intra-ocular injection of 140 nmol KA and compared to
      that of control and untreated retinas. In the normal retina, the majority of GABA
      positive cells (79%) were located in the inner nuclear layer (INL), in one to
      four cell rows next to the inner plexiform layer (IPL), and in one cell row next
      to the outer plexiform layer (OPL). The remainder (21%) were found in the
      ganglion cell layer (GCL). Dense immunoreactivity was seen throughout the IPL. In
      the OPL, stained dots and occasional immunoreactive large processes could be
      seen. KA-exposed retinas processed for GABA immunocytochemistry 5 and 24 h after
      the injection showed an 85% reduction in the number of GABA immunoreactive cells.
      About the same degree of depletion was seen among GABA-IR cells located at
      different retinal levels. However, at these survival times, immunostaining was
      observed in three distinct bands in the IPL, indicating that the vulnerability to
      KA is not uniformly distributed among all GABAergic cells. At 48 h, an additional
      decrease in the number of labelled cells was noted, but immunoreactive cells were
      still found both in the INL and GCL. Even 6 days after KA treatment, a few
      stained cell bodies were seen in the INL next to the IPL, as well as a few
      processes in the IPL. The study shows that KA receptor overstimulation induces a
      marked depletion of the endogenous cellular GABA pools of the central rabbit
      retina, most likely as a result of GABAergic cell loss. However, a small
      population of GABAergic cells located in the INL appears to be less vulnerable to
      the toxic effects of 140 nmol KA.

PMID- 7813662
TI  - The role of putamen and pallidum in motor initiation in the cat. I. Timing of
      movement-related single-unit activity.
AB  - The participation of basal ganglia in motor initiation was studied in six cats
      operantly trained to perform a ballistic flexion movement, triggered after a
      brief sound in a simple reaction time condition or delayed after the same sound
      in the presence of a tone cue. The activity of 356 neurons was recorded in the
      putamen and in the pallidum (globus pallidus and entopeduncular nucleus). A total
      of 19.4% of the neurons were not related to the conditioned flexion movement:
      they were either unrelated to the task (10.1%) or related to other periods of the
      motor performance such as trial beginning or reward delivery (9.3%). About 60% of
      the remaining neurons--defined as task-related--exhibited changes in firing rate
      that occurred, in the reaction time condition, less than 100 ms after the go
      signal and therefore began prior to movement onset. For most neurons, in the
      delayed condition, these early changes were absent, suggesting that their
      occurrence in the reaction time condition was not a sensory response but rather
      was related to the movement initiation. In addition, for many neurons these
      changes shifted in time, remaining time-locked to the movement. Correlations
      between these early changes in activity and motor parameters were demonstrated,
      suggesting that these changes were movement-related. For most neurons the firing
      levels observed during intertrial intervals and during foreperiod were similar.
      The mean discharge rate during the foreperiod was 19.2 impulses/s. Three patterns
      of activity were observed before movement: increases in discharge rate (61% of
      task-related neurons), transient decreases followed by increases (11%), or
      prolonged decreases (28%). Only minor differences were found between the
      characteristics of the populations of neurons recorded in the three sites under
      study: on average the neurons recorded in the globus pallidus were more active
      than the neurons recorded in the putamen or in the entopeduncular nucleus. The
      fact that, for certain neurons, the changes of activity prior to movement were
      different in reaction time condition and in delayed condition showed that the
      pattern of activity preceding movement might depend on the temporal requirements
      for motor initiation. Taken together with the motor effects obtained in the same
      task following GABA-receptor activation with muscimol microinjections in these
      structures, the present results suggest that putamen and pallidal neurons
      participate in the initiation of the conditioned movement under study.

PMID- 7813663
TI  - High molecular weight tau distribution and microtubule stability in neuroblastoma
      N115 cells.
AB  - The localization of high molecular weight (HMW) tau proteins in neuroblastoma
      N115 cells and of their transcripts was compared to that of non-tyrosinated and
      tyrosinated tubulin before and after treatment with depolymerizing drugs.
      Microtubules stained by tau antibodies were present both in a limited region of
      the cell center and in the cell processes, whereas tau transcripts were detected
      only in the cell body. The microtubules localized in the cell center and labeled
      by tau antibodies resisted colcemid treatment, whereas those in the neurites were
      completely depolymerized by the drug. Microtubules containing stable and unstable
      microtubule tracts were identified in the neurites after colcemid treatment.
      These composite microtubules were not labeled by tau antibodies. It is concluded
      that stable and unstable polymers--localized in the cell center and in the
      neurites, respectively--contain HMW tau proteins, whereas composite microtubules
      displayed in the cell processes do not. Microtubule stability in this cell line
      does not therefore seem to be related to the association of tau proteins to the
      polymers but, rather, to posttranslational modifications of the tubulin subunits.

PMID- 7813664
TI  - Corticothalamic influences on transmission of tactile information in the
      ventroposterolateral thalamus of the cat: effect of reversible inactivation of
      somatosensory cortical areas I and II.
AB  - The influence of the corticothalamic projections from somatosensory areas I and
      II (SI and SII) on the transmission of tactile information through the
      ventroposterolateral (VPL) thalamus was investigated by examining the effects of
      cooling-induced, reversible inactivation of SI and/or SII on the responsiveness
      of 32 VPL neurons to controlled tactile stimulation of the distal forelimb in
      anaesthetized cats. Both the response levels and spontaneous activity were
      unaffected in 21 (66%) of the VPL neurons as a result of inactivation of SI or
      SII singly, or both SI and SII simultaneously. In the remaining 11 neurons, 10
      displayed a reduction in response level, an effect observed over the whole of the
      stimulus-response relations for the neurons studied at different stimulus
      amplitudes, and one neuron displayed an increase in response level in association
      with cortical inactivation. When responses in VPL neurons were affected by
      inactivation of one cortical somatosensory area, they were not necessarily
      affected by inactivation of the other. Of 14 neurons studied for the effects of
      the separate inactivation of SI alone and of SII alone, 7 were affected, one from
      both areas, but the remaining 6 were affected by inactivation of only one of
      these areas. Phaselocking, and therefore the precision of impulse patterning in
      the responses of VPL neurons to skin vibration, was unchanged by the cortical
      inactivation irrespective of whether the response level was affected. The results
      suggest that SI and SII may exert a facilitatory influence on at least a third of
      VPL neurons and in this way may modulate the gain of transmission of tactile
      signalling through the thalamus.

PMID- 7813665
TI  - Expression of major histocompatibility complex class II antigen on amoeboid
      microglial cells in early postnatal rat brain following intraperitoneal
      injections of lipopolysaccharide.
AB  - In rats given two single intraperitoneal injections of lipopolysaccharide (LPS)
      at 1 and 4 days of age and killed at 7 days of age, 11.5--12% of amoeboid
      microglial cells (AMC) in the supraventricular corpus callosum were induced to
      express major histocompatibility complex (MHC) class II antigen, as detected with
      monoclonal antibody OX-6. The MHC class II antigen induced was colocalized with
      MHC class I antigen and type 3 complement receptors on the same cells. The
      expression of MHC class II antigen on the plasma membrane of AMC was confirmed in
      immunoelectron microscopy. Although OX-6-positive AMC often assumed a
      perivascular position, the majority of them, however, were far removed from the
      blood vessels. The cytoplasmic processes of the perivascular OX-6-positive AMC
      appeared to rest directly on the vascular lamina, and in some section profiles
      they were in contact with a large surface area of the outer wall of small blood
      vessels. It is concluded from this study that although MHC class II antigen is
      not constitutively present on AMC, it is, however, inducible under stimulation
      with LPS. It is, therefore, suggested that the OX-6-positive AMC, especially the
      perivascular AMC, may have the potentiality to function as antigen-presenting
      cells in the developing brain when challenged by LPS.

PMID- 7813666
TI  - Transfer of short-term adaptation in human saccadic eye movements.
AB  - Controversy exists as to the extent to which the saccadic system, adapted in the
      so-called 'gain-shortening paradigm' for a particular target configuration,
      transfers the resulting change in saccade metrics to saccades elicited under
      different circumstances. In order to further assess this problem, we investigated
      the properties of human saccadic eye movements after visually induced short-term
      adaptation under a variety of conditions. We observed that saccades both during
      and after the adaptation did not significantly change their main sequence
      properties with respect to the pre-adaptation baseline. Saccade velocity profiles
      remained normal throughout the experiment, and we obtained no evidence that
      correction saccades were gradually absorbed in the primary saccade. We found that
      the effect of the short-term adaptation on saccade metrics is not confined to the
      particular combination of initial eye position and spatial position of the visual
      target used to induce the adaptation response. Saccades elicited from different
      initial positions towards targets with the same retinotopic coordinates as in the
      adaptation phase yield the same level of adaptation. However, our findings
      indicate that adaptation is confined to a limited range of saccade vectors around
      the oculocentric coordinates of the adaptation target ('restricted adaptation
      field'). Smaller and larger saccades are endowed with significantly lower
      adaptation values. Moreover, two further experiments showed that a retinal
      stimulus is not a prerequisite for adaptation to express itself: First, in a
      double-step experiment, we dissociated the retinal stimulus vector from the
      required oculomotor response. Second, we also investigated the effect of visually
      induced adaptation on auditory evoked saccades. In both tasks the adaptation was
      transferred to the required motor response. Based on our findings, we conclude
      that short-term adaptation is expressed at a multisensory stage, where saccadic
      eye movements are represented as desired eye displacement vectors (motor error).
      Possible neurophysiological implications are discussed.

PMID- 7813668
TI  - Short-term vestibulo-ocular reflex adaptation in humans. I. Effect on the ocular
      motor velocity-to-position neural integrator.
AB  - We investigated the effect of short-term vestibulo-ocular reflex (VOR) adaptation
      in normal human subjects on the dynamic properties of the velocity-to-position
      ocular motor integrator that holds positions of gaze. Subjects sat in a
      sinusoidally rotating chair surrounded by an optokinetic nystagmus drum. The
      movement of the visual surround (drum) was manipulated relative to the chair to
      produce an increase (x 1.7 viewing), decrease (x 0.5, x 0 viewing), or reversal
      (x (-2.5) viewing) of VOR gain. Before and after 1 h of training, VOR gain and
      gaze-holding after eccentric saccades in darkness were measured. Depending on the
      training paradigm, eccentric saccades could be followed by centrifugal drift
      (after x 0.5 viewing), implying an unstable integrator, or by centripetal drift
      [after x 1.7 or x (-2.5) viewing], implying a leaky integrator. The changes in
      the neural integrator appear to be context specific, so that when the VOR was
      tested in non-training head orientations, both the adaptive change in VOR gain
      and the changes in the neural integrator were much smaller. The changes in VOR
      gain were on the order of 10% and the induced drift velocities were several
      degrees per second at 20 deg eccentric positions in the orbit. We propose that
      (1) the changes in the dynamic properties of the neural integrator reflect an
      attempt to modify the phase (timing) relationships of the VOR and (2) the
      relative directions of retinal slip and eye velocity during head rotation
      determine whether the integrator becomes unstable (and introduces more phase lag)
      or leaky (and introduces less phase lag).

PMID- 7813667
TI  - Reflex responses of motor units in human masseter muscle to mechanical
      stimulation of a tooth.
AB  - The reflex responses evoked by controlled mechanical stimulation of an upper
      central incisor tooth in single motor units in the human masseter muscle were
      examined. The stimuli were (brisk) taps and (slow) pushes of about 2 N peak
      force, applied orthogonally to the labial surface of the ipsilateral upper
      central incisor tooth. The reflex responses of the motor units were characterised
      by analysis of the changes in the durations of the first and second interspike
      intervals (ISIs) immediately following the stimulus. A significant increase in
      the duration of these ISIs in comparison with pre-stimulus ISIs indicated
      inhibition, and significant shortening indicated excitation. Twenty masseter
      motor units were tested with both the pushes and the taps. The brisk taps
      elicited a significant reflex inhibition in 16 of the 20 motor units at a latency
      of 13 ms and duration of 37 ms. This inhibition was followed by significant
      excitation in 11 of the 20 units at latencies of 71 ms, lasting for 29 ms. The
      short-latency response to slow pushes was significant inhibition in four units:
      significant excitation in one unit and no response in 15 units. The slow pushes
      evoked a significant long-latency excitatory reflex response in 12 of the 20
      units at latencies of 77 ms and lasting for 40 ms. The shapes and amplitudes of
      the compound post-synaptic potentials underlying the reflex responses in the
      motoneurones were estimated. It is concluded that stimulation of periodontal
      mechanoreceptors usually activates an excitatory reflex pathway to the jaw
      closing motoneurones. This probably helps to grip the food bolus between the
      teeth during chewing. However, when the rate of application of the stimulus is
      large enough, a short-latency inhibitory response is evoked which, if of
      sufficient duration, may over-ride the subsequent excitatory response. Inhibition
      of the jaw-closing muscles will tend to protect the teeth and soft tissues when
      one bites unexpectedly on a hard object while chewing.

PMID- 7813669
TI  - Short-term vestibulo-ocular reflex adaptation in humans. II. Error signals.
AB  - We oscillated humans sinusoidally at 0.2 Hz for 1 h, using various combinations
      of rotations of the head and visual surround to elicit short-term adaptation of
      the gain of the vestibulo-ocular reflex (VOR). Before and after each period of
      training, the gain of the VOR was measured in darkness, in response to a position
      step of head rotation. A small foveal target served as well as a full-field
      stimulus at driving VOR adaptation. Oscillation of the visual surround alone
      produced a substantial increase in the VOR gain. When the visual scene was
      rotated in phase with the head but with a larger amplitude to produce a reversal
      of the VOR, the VOR gain increased if the movement of the visual scene was much
      greater than that of the head, otherwise the gain decreased. We interpreted these
      results with a model of VOR adaptation that uses as its "error signal" the
      combination of motion of images on the retina (retinal slip) and any additional
      slow-phase eye velocity, beyond that generated by the VOR through the vestibular
      nuclei, necessary to prevent such retinal slip during head rotation. The slow
      phase velocity generated by the VOR is derived from "inferred head rotation", a
      signal based on the discharge of neurons in the vestibular nuclei that receive
      both labyrinthine and visual (optokinetic) inputs. The amplitude and sign of the
      ratio of the "error signal" to "inferred head velocity" determined the amplitude
      and the direction (increase or decrease) of VOR gain adaptation.

PMID- 7813670
TI  - Not looking while leaping: the linkage of blinking and saccadic gaze shifts.
AB  - Many vertebrates generate blinks as a component of saccadic gaze shifts. We
      investigated the nature of this linkage between saccades and blinking in normal
      humans. Activation of the orbicularis oculi, the lid closing muscle, EMG occurred
      with 97% of saccadic gaze shifts larger than 33 degrees. The blinks typically
      began simultaneously with the initiation of head and/or eye movement. To minimize
      the possibility that the blinks accompanying saccadic gaze shifts were reflex
      blinks evoked by the wind rushing across the cornea and eye-lashes as the head
      and eyes turned, the subjects made saccadic head turns with their eyes closed. In
      this condition, orbicularis oculi EMG activity occurred with all head turns
      greater than 17 degrees in amplitude and the EMG activity began an average of
      39.3 ms before the start of the head movement. Thus, one component of the command
      for large saccadic gaze shifts appears to be a blink. We call these blinks gaze
      evoked blinks. The linkage between saccadic gaze shifts and blinking is
      reciprocal. Evoking a reflex blink prior to initiating a voluntary saccadic gaze
      shift dramatically reduces the latency of the initiation of the head movement.

PMID- 7813671
TI  - Task-dependent differences between mono- and bi-articular heads of the triceps
      brachii muscle.
AB  - We studied motor-unit recruitment and decruitment thresholds in the three heads
      of the human elbow extensor, the triceps brachii muscle (caput mediale and
      laterale, both mono-articular heads, and caput longum, the bi-articular head) by
      means of intramuscular electromyographic-recordings. Two experiments were
      performed: an 'isometric' and a 'movement' experiment. In the isometric
      experiment, subjects were asked to increase the elbow extension torque
      isometrically to a specific level, keep the torque at the level for 10 s, and
      then decrease the torque again to zero. In the movement experimental subjects
      moved their forearm from 90 degrees to 110 degrees extension against an
      increasing flexion torque, kept the latter position for 10 s and then moved their
      forearm back while the torque decreased. Results for caput longum showed that
      recruitment thresholds were higher than decruitment thresholds, whereas in caput
      mediale and laterale no difference in thresholds was found. In caput longum
      recruitment thresholds were found to be lower in movement conditions than in
      isometric conditions. The reverse effect was observed in caput mediale, whereas
      no difference in recruitment thresholds was found in caput laterale. Our results
      point to a transfer of force from mono-articular muscles in isometric conditions
      to bi-articular muscles in movement conditions. A similar transfer is found when
      recruitment and decruitment are compared. This means that the transfer is not
      only a property of the elbow-flexor muscles, but is a more common trait. A
      qualitative analysis of firing frequencies at recruitment and at decruitment in
      both conditions supports our findings.

PMID- 7813672
TI  - The effects of practice on movement distance and final position reproduction:
      implications for the equilibrium-point control of movements.
AB  - Predictions of two views on single-joint motor control, namely programming of
      muscle force patterns and equilibrium-point control, were compared with the
      results of experiments with reproduction of movement distance and final location
      during fast unidirectional elbow flexions. Two groups of subjects were tested.
      The first group practiced movements over a fixed distance (36 degrees), starting
      from seven different initial positions (distance group, DG). The second group
      practiced movements from the same seven initial positions to a fixed final
      location (location group, LG). Later, all the subjects were tested at the
      practiced task with their eyes closed, and then, unexpectedly for the subjects,
      they were tested at the other, unpracticed task. In both groups, the task to
      reproduce final position had lower indices of final position variability than the
      task to reproduce movement distance. Analysis of the linear regression lines
      between initial position and final position (or movement distance) also
      demonstrated a better (more accurate) performance during final position
      reproduction than during distance reproduction. The data are in a good
      correspondence with the predictions of the equilibrium-point hypothesis, but not
      with the predictions of the force-pattern control approach.

PMID- 7813673
TI  - Illusory contours and linear filters.
AB  - The border between two abutting gratings is sometimes referred to as an illusory
      contour. In the Fourier spectrum of such a pattern there is no energy
      corresponding to the precise orientation of this contour. Neuronal responses
      elicited by such stimuli are therefore thought to be incompatible with linear
      filtering. The present investigation tested this notion. Abutting gratings were
      Fourier analyzed and passed through spatial and temporal filters with properties
      comparable with those of cortical neurons. It was found that the distribution of
      amplitudes in the Fourier spectrum is such that these stimuli may indeed
      stimulate neurons based on linear filtering. In the case of drifting stimuli the
      amount of stimulation may be maximal when the illusory contour is at the optimal
      orientation for bars with less stimulation on either side of this orientation.

PMID- 7813674
TI  - Feedback inhibition in the cat's lateral geniculate nucleus.
AB  - Feedback inhibition is generally believed to be a ubiquitous feature of brain
      circuitry, but few specific instances have been documented. An example in cats is
      the supposed feedback circuit involving relay cells of the lateral geniculate
      nucleus and cells of the perigeniculate nucleus (a part of the thalamic reticular
      nucleus): geniculate relay cells innervate the perigeniculate nucleus, which, in
      turn, provides an inhibitory, GABAergic projection back to the lateral geniculate
      nucleus. However, feedback inhibition at the single-cell level requires that a
      given perigeniculate cell project back onto the same geniculate relay cell that
      innervates it. We probed for this in an in vitro slice preparation of the cat's
      lateral geniculate nucleus. We evoked a single action potential in a geniculate
      cell via a brief, depolarizing pulse delivered through an intracellular recording
      electrode and looked for any evoked hyperpolarizations. For 6 of the 36
      geniculate cells tested, we observed a long-lasting hyperpolarization after the
      action potential, and much of this was eliminated by application of bicuculline,
      suggesting synaptically activated inhibitory postsynaptic potentials. We
      interpreted this to be clear evidence that a given neuron may inhibit itself via
      circuitry mediating feedback inhibition in the cat's lateral geniculate nucleus.

PMID- 7813675
TI  - Interstitial and tissue cations and electrical potential after experimental
      spinal cord injury.
AB  - Interstitial and tissue cations and electrical potential were studied in an
      experimental model of spinal cord contusion injury in anaesthetised cats.
      Measurements of interstitial ion activity in the grey matter at the injury site
      (with ion-selective electrodes), showed a decrease of sodium and calcium, an
      increase of potassium, a small acidification and a negative shift in the
      electrical potential 5 min after injury. The interstitial ionic changes were
      completely reversible within 90 min following injury. Measurements of the ion
      content in a tissue sample from the injury site (flame photometry) showed an
      increase of sodium and calcium and a decrease of potassium 5 min after injury.
      The magnitude of the post-injury sodium change was much larger than the potassium
      change, both for interstitial and tissue measurements. Treatment of the animals
      with the calcium entry blocker flunarizine before the injury did not influence
      the magnitude of post-injury interstitial calcium decrease but significantly
      increased the rate of subsequent recovery. Pre-injury flunarizine treatment also
      significantly increased the recovery rate of the electrical potential. The
      experiments suggest the occurrence of a net ionic shift towards the intracellular
      space, which may contribute to oedema formation in the very early post-injury
      period. The post-injury decrease of interstitial calcium activity is probably not
      mediated by flunarizine-sensitive calcium entry mechanisms; such mechanisms may,
      however, be involved in the subsequent recovery period for interstitial calcium
      activity. Calcium ions may be involved in the recovery process of the negative
      electrical potential after injury.

PMID- 7813676
TI  - Spontaneous and stimulus-triggered epileptic discharges: delayed antiepileptic
      effect with triggering.
AB  - The aim of the present study was to test whether the organic calcium channel
      blocker verapamil acts not only on spontaneously occurring epileptiform field
      potentials (EFP) but also on EFP triggered by single electrical stimuli in the
      low-Mg2+ epilepsy model. The experiments were carried out on hippocampal slices
      of guinea pigs. EFP were elicited by omission of Mg2+ from the perfusate and
      recorded from stratum pyramidale and stratum radiatum in the CA1 subfield. Single
      electrical stimuli were applied to the Schaffer collateral pathway. Verapamil was
      added to the bath solution in concentrations of 40 and 60 mumol verapamil/l at
      normal (4 mmol/l) and elevated (8 mmol/l) K+ levels. After omission of Mg2+ from
      the perfusate, spontaneously occurring EFP appeared in all trials. These
      spontaneously occurring EFP were suppressed dose-dependently upon addition of
      verapamil to the perfusate. At elevated K+ levels, the latencies to suppression
      were significantly reduced and the dose dependency was abolished for the two
      doses of verapamil used. Triggered EFP reappeared upon stimulation after
      spontaneously occurring EFP had been suppressed, except for trials with 60 mumol
      verapamil/l bath solution with elevated K+ levels. The stimulus-evoked EFP were
      abolished with continuing perfusion of verapamil except for trials with 40
      mumol/l at normal extracellular K+ concentrations. This effect was again dose
      dependent and enhanced by elevating the K+ level. In all experiments, stimulus
      evoked EFP reappeared upon wash-out of verapamil. A primary action of verapamil
      on pacemaker functions in epileptogenic tissue is assumed.

PMID- 7813677
TI  - Seizure suppression in kindling epilepsy by intracerebral implants of GABA- but
      not by noradrenaline-releasing polymer matrices.
AB  - Gamma-aminobutyric acid (GABA)-releasing polymer matrices were implanted
      bilaterally, immediately dorsal to the substantia nigra, in rats previously
      kindled in the amygdala. Two days after implantation, rats with GABA-releasing
      matrices exhibited only focal limbic seizures in response to electrical
      stimulation, whereas animals with control matrices devoid of GABA had generalized
      convulsions. GABA release from the polymer matrices was high during the first
      days after implantation, as demonstrated both in vitro and, using microdialysis,
      in vivo. The anticonvulsant effect was no longer observed at 7 and 14 days at
      which time GABA release was found to be low. In a parallel experiment, polymer
      matrices containing noradrenaline (NA) were implanted bilaterally into the
      hippocampus of rats with extensive forebrain NA depletion induced by an
      intraventricular 6-hydroxydopamine injection. No effect on the development of
      hippocampal kindling was observed, despite extracellular NA levels exceeding
      those of rats with intrahippocampal locus coeruleus grafts that have previously
      been shown to retard kindling rate. The results indicate that GABA-releasing
      implants located in the substantia nigra region can suppress seizure
      generalization in epilepsy, even in the absence of synapse formation and
      integration with the host brain. In contrast, the failure of NA-releasing polymer
      matrices to retard the development of seizures in NA-depleted rats suggests that
      such an effect can only be exerted by grafts acting through a well-regulated,
      synaptic release of NA.

PMID- 7813678
TI  - Direct monitoring of dopamine and 5-HT release in substantia nigra and ventral
      tegmental area in vitro.
AB  - Fast-scan cyclic voltammetry with carbon fibre microelectrodes was used to detect
      endogenous dopamine (DA) and 5-hydroxytryptamine (5-HT) release from three
      distinct regions of guinea-pig mid-brain in vitro: rostral and caudal substantia
      nigra (SN) and the ventral tegmental area (VTA). Previous electrophysiological
      studies have demonstrated that cells of the caudal SN and the VTA have similar
      characteristics, whereas cells in the rostral SN have distinctly different
      properties. In the present study, we confirmed that each region has tyrosine
      hydroxylase-positive neurons and determined, using high-performance liquid
      chromatography, that DA levels were similar in rostral and caudal SN, but lower
      in SN than in VTA. In each region, application of veratrine, which was shown by
      intracellular recordings to have a reversible depolarising action, evoked a
      signal attributable to DA and distinguishable from that of 5-HT. Release signals
      were monitored every 250 ms with a spatial resolution of less than 50 microns.l
      DA release was calcium-dependent and was not detectable in a catecholamine-poor
      area such as the cerebellum, or in mid-brain tissue pre-treated with reserpine.
      Within the normal mid-brain, the amount of DA released was correlated with tissue
      content in that it was higher in the VTA than in either region of SN. It is
      concluded that DA released from somato-dendritic parts of mid-brain neurons
      exhibits site-specific variation. This is the first report of direct monitoring
      of DA and 5-HT release from these regions with in situ electrodes and
      demonstrates the utility of fast-scan cyclic voltammetry to investigate the
      mechanisms and possible non-classical functions of somato-dendritic DA release.

PMID- 7813679
TI  - Membrane ionic currents and properties of freshly dissociated rat brainstem
      neurons.
AB  - It is well known that neuronal firing properties are determined by synaptic
      inputs and inherent membrane functions such as specific ionic currents. To
      characterize the ionic currents of brainstem cardio-respiratory neurons, cells
      from the hypoglossal (XII) nucleus and the dorsal motor nucleus of the vagus
      (DMX) were freshly dissociated and membrane ionic currents were studied under
      whole-cell voltage and current clamp. Both of these neurons showed a TTX
      sensitive Na+ current with a much larger current density in XII than DMX neurons.
      This Na+ current had two (fast and slow) distinct inactivation decay components.
      The ratio of the magnitudes of the fast to slow component was roughly two-fold
      greater in DMX than in XII cells. Both DMX and XII neurons also showed a high
      voltage-activated Ca2+ current, but this current density was significantly
      greater (three-fold) in DMX than XII neurons. A relatively small amount of low
      voltage activated Ca2+ current was also observed in DMX neurons, but not in the
      majority of XII cells. A transient and a sustained outward current components
      were observed in DMX cells, but only sustained currents were present in XII
      neurons. These outward currents had a reversal potential of about -70 mV with 3
      mM external K+ and -30 mV with 25 mM K+, and substitution of K+ with cesium and
      tetraethylammonium suppressed more than 90% the outward currents, indicating that
      most outward currents were carried by K+. The transient outward current consisted
      of two components with one sensitive to 4-aminopyridine and the other to
      intracellular Ca2+. In XII neurons, BRL 38227 (lemakalim), an ATP-sensitive K+
      (KATP) channel activator, increased the sustained K+ currents by 10% of control,
      and glibenclamide, a KATP channel blocker, decreased the sustained K+ currents by
      20%. Evidence for the presence of an inward rectifier K+ current was also
      obtained from both XII and DMX neurons. These results on XII and DMX neurons
      indicate that (1) the methods used to dissociate neurons provide a useful means
      to overcome voltage clamp technical difficulties; (2) ion channel characteristics
      such as density and biophysical properties of DMX neurons are very different from
      those of XII neurons; and (3) several newly discovered membrane ionic currents
      are present in these cells.

PMID- 7813680
TI  - Morphological characteristics of cultured olfactory bulb cells.
AB  - Cultured olfactory bulb cells from embryonic mice had ultrastructural
      characteristics similar to those of many cell types in the intact adult mouse
      olfactory bulb. Identified cultured cells included mitral/tufted cells, granule
      cells, short-axon cells, and fibrous and protoplasmic astrocytes. Cultured
      neurons were found as individual cells, clusters or aggregates. Clusters
      consisted of a loose array of neurons that appeared to be densely interconnected
      by neurites. However, few neurites or fascicles emanated from clusters to
      adjoining areas. Aggregates consisted of many small, usually rounded, neurons
      piled on top of one larger neuron, or on more than one, with typically many
      neurites and fascicles projecting to adjacent aggregates, clusters or individual
      neurons. Neurites of cultured olfactory bulb cells were well developed, and some
      were several millimeters long. Synapses were very prominent in these cultures,
      especially in aggregates, clusters, and fascicles. Electron-lucent, dense-core,
      and coated vesicles were present. Polarity, shape, and length of the long axis
      (size) of 815 cultured neurons, identified by positive anti-microtubule
      associated protein 2 staining, were documented. Cultured neurons varied in size
      from 9 to 27 microns, with an average size of 16 microns. Elliptical bipolar
      (35%), triangular multipolar (21%), and round unipolar (15%) were the most common
      polarity/shape combinations found in culture. Multipolar, triangular, triangular
      multipolar, and elliptical bipolar cells increased in size with increasing age of
      culture. The relative proportions of triangular, multipolar, elliptical
      multipolar, and triangular multipolar cells decreased, whereas the relative
      proportions of round, unipolar, and round unipolar cells increased with
      increasing age of culture. These changes in population subtypes and cell size may
      indicate continued differentiation and maturation of cultured neurons.

PMID- 7813681
TI  - An investigation of depotentiation of long-term potentiation in the CA1 region of
      the hippocampus.
AB  - We have investigated long-term synaptic depression in the CA1 region of rat
      hippocampal slices. Prolonged low-frequency stimulation (LFS; 900 stimuli
      delivered at 2 Hz) of the Schaffer collateral-commissural pathway in naive slices
      did not induce long-term depression (LTD) of synaptic transmission. However, if
      long-term potentiation (LTP) was firstly induced in the pathway then LFS
      generated an LTD-like effect (i.e. depotentiation of LTP). Depotentiation could
      be induced 2 h (the longest time studied) after the induction of LTP and was
      stable for the duration of the experiment (followed for up to 40 min). The
      induction of depotentiation was not blocked by the N-methyl-D-aspartate receptor
      antagonist D-2-amino-5-phosphonopentanoate, the L-type voltage-gated Ca2+ channel
      blocker nimodipine or the nitric oxide synthase inhibitor N omega-nitro-L
      arginine. However, the magnitude of depotentiation was reversibly reduced, in a
      stereoselective manner, by the specific metabotropic glutamate receptor (mGluR)
      antagonist (+)-alpha-methyl-4-carboxyphenylglycine. These results show that
      prolonged low frequency stimulation can result in an mGluR-dependent
      depotentiation of LTP.

PMID- 7813682
TI  - Phasic stimulation of the locus coeruleus: effects on activity in the lateral
      geniculate nucleus.
AB  - Neurons in the locus coeruleus (LC) encode information related to behavioral
      state in a tonic pattern of firing and information related to the occurrence of a
      sensory stimulus in a phasic pattern of firing. The effects of phasic stimulation
      of the LC (6 pulses at 30 Hz), designed to approximate its physiological
      activation by sensory stimuli, were studied in the lateral geniculate nucleus
      (LGN) of anesthetized rats. Phasic stimulation of the LC significantly increased
      neuronal firing in the LGN with a mean latency 320 ms from onset of stimulation.
      Receiver operating characteristic analyses on a trial-by-trial basis showed that
      phasic LC stimulation can result in a highly discriminable signal in the LGN.
      This increased neuronal firing rate in the LGN was specific for the site of
      stimulation and was reduced by the norepinephrine synthesis inhibitor alpha
      methyl-p-tyrosine and by intravenous WB-4101 (alpha 1-receptor antagonist).
      Neurons in the LGN have a single-spike firing mode when sensory information is
      faithfully relayed from retina to cortex and a burst-firing mode when the
      transfer of this information is degraded. Phasic LC stimulation reduced burst
      firing (2-5 ms interspike intervals, ISIs) at low frequencies (< or = 4 Hz) in
      the LGN, and for some neurons there was an absolute decrease in burst-like ISIs
      after LC stimulation, despite an increase in mean firing rate.

PMID- 7813683
TI  - Effects of muscimol inactivation of the cerebellar interposed-dentate nuclear
      complex on the performance of the nictitating membrane response in the rabbit.
AB  - Intracranial microinjections of the GABAA agonist muscimol were used to assess
      the involvement of the dentato-interposed cerebellar nuclear complex in the
      performance of the conditioned (CR) and unconditioned (UR) nictitating membrane
      responses in the rabbit. Specifically, the experiments test the hypothesis that
      the cerebellar nuclei are involved in the performance of both the CRs and URs.
      The experiments employed temporary nuclear lesions to disrupt the CRs in order to
      examine parallel effects on URs. Animals were conditioned in a standard delay
      conditioning paradigm. Injection sites at which the muscimol application
      disrupted execution of the CRs were identified in each rabbit. Once these sites
      were found, the effects of muscimol and saline injections were evaluated while
      alternating paired trials with unpaired trials in which only the unconditioned
      stimuli were applied. There are two main findings in the present study. First,
      the activation of the GABAA receptors in the dentato-interposed cerebellar
      nuclear region reduced the amplitude and increased the latency of the UR. This
      change in the UR closely paralleled the disruption of the CR. This observation is
      consistent with the notion that the cerebellum is involved in the regulation of
      defensive flexion reflexes. Second, cerebellar nuclear inactivation did not
      eliminate the tone-induced enhancement of the UR. This finding suggests the
      presence of cerebellum-independent circuits subserving the intermodal interaction
      between the conditioned and unconditioned stimuli.

PMID- 7813684
TI  - Human ocular responses to translation of the observer and of the scene:
      dependence on viewing distance.
AB  - Recent experiments on monkeys have indicated that the eye movements induced by
      brief translation of either the observer or the visual scene are a linear
      function of the inverse of the viewing distance. For the movements of the
      observer, the room was dark and responses were attributed to a translational
      vestibulo-ocular reflex (TVOR) that senses the motion through the otolith organs;
      for the movements of the scene, which elicit ocular following, the scene was
      projected and adjusted in size and speed so that the retinal stimulation was the
      same at all distances. The shared dependence on viewing distance was consistent
      with the hypothesis that the TVOR and ocular following are synergistic and share
      central pathways. The present experiments looked for such dependencies on viewing
      distance in human subjects. When briefly accelerated along the interaural axis in
      the dark, human subjects generated compensatory eye movements that were also a
      linear function of the inverse of the viewing distance to a previously fixated
      target. These responses, which were attributed to the TVOR, were somewhat weaker
      than those previously recorded from monkeys using similar methods. When human
      subjects faced a tangent screen onto which patterned images were projected, brief
      motion of those images evoked ocular following responses that showed
      statistically significant dependence on viewing distance only with low-speed
      stimuli (10 degrees/s). This dependence was at best weak and in the reverse
      direction of that seen with the TVOR, i.e., responses increased as viewing
      distance increased. We suggest that in generating an internal estimate of viewing
      distance subjects may have used a confounding cue in the ocular-following
      paradigm--the size of the projected scene--which was varied directly with the
      viewing distance in these experiments (in order to preserve the size of the
      retinal image). When movements of the subject were randomly interleaved with the
      movements of the scene--to encourage the expectation of ego-motion--the
      dependence of ocular following on viewing distance altered significantly: with
      higher speed stimuli (40 degrees/s) many responses (63%) now increased
      significantly as viewing distance decreased, though less vigorously than the
      TVOR. We suggest that the expectation of motion results in the subject placing
      greater weight on cues such as vergence and accommodation that provide veridical
      distance information in our experimental situation: cue selection is context
      specific.

PMID- 7813685
TI  - Fingertip contact influences human postural control.
AB  - Touch and pressure stimulation of the body surface can strongly influence
      apparent body orientation, as well as the maintenance of upright posture during
      quiet stance. In the present study, we investigated the relationship between
      postural sway and contact forces at the fingertip while subjects touched a rigid
      metal bar. Subjects were tested in the tandem Romberg stance with eyes open or
      closed under three conditions of fingertip contact: no contact, touch contact (<
      0.98 N of force), and force contact (as much force as desired). Touch contact was
      as effective as force contact or sight of the surroundings in reducing postural
      sway when compared to the no contact, eyes closed condition. Body sway and
      fingertip forces were essentially in phase with force contact, suggesting that
      fingertip contact forces are physically counteracting body sway. Time delays
      between body sway and fingertip forces were much larger with light touch contact,
      suggesting that the fingertip is providing information that allows anticipatory
      innervation of musculature to reduce body sway. The results are related to
      observations on precision grip as well as the somatosensory, proprioceptive, and
      motor mechanisms involved in the reduction of body sway.

PMID- 7813687
TI  - Cycloversion and cyclovergence: the effects of the area and position of the
      visual display.
AB  - Rotation of a display in the frontal plane evokes a conjugate nystagmic rotation
      of the eyes (cycloversion) about the visual axes, with slow phases in the
      direction of stimulus motion--a response known as torsional optokinetic nystagmus
      (TOKN). Antiphase rotation of large dichoptic displays evokes a disconjugate
      rotation of the eyes about the visual axes, a response known as cyclovergence.
      Using the scleral-coil technique for monitoring eye movements we recorded TOKN
      evoked by black-and-white sectored displays rotating about the visual axis at an
      angular velocity of 30 degrees/s. The display was confined to central areas with
      diameters ranging from 5 degrees to full field or with the central 5 degrees to
      75 degrees occluded. A 5 degrees central display evoked TOKN with 40% of the gain
      for the full-field display and gain increased as a function of the size of the
      display. The gain of TOKN decreased with increasing size of a central occluder.
      These characteristics of TOKN are similar to those of horizontal OKN.
      Cyclovergence was virtually absent with a 5 degrees display but was immune to
      occlusion of the central 40 degrees. Cyclovergence therefore differs from
      cycloversion in showing no preference for centrally placed stimuli. These effects
      are free from the influence of stationary edges, since these were concentric with
      the stimulus motion. The effects are also free from the influence of voluntary
      pursuit, since humans do not normally have voluntary control over torsional eye
      movements.

PMID- 7813686
TI  - Recruitment order of motoneurons during functional tasks.
AB  - The recruitment order of motoneurons of first dorsal interosseous (1DI) muscle
      has been shown to be the same during either isometric abduction or flexion of the
      index finger. However, it is not known whether this stereotyped recruitment is
      the same for all functional tasks. This question was addressed by using the 1DI
      muscle, which contributes to many functional tasks involving the hand and
      fingers. Single motor units and surface electromyographic activity were recorded
      from 1DI in three human subjects. Each subject performed tasks of abduction of
      the index finger, rotation to unscrew a threaded knob and pincer to close a
      spring-loaded clip. The same motor units were activated for each of the three
      tasks, providing no evidence for the existence of task groups. The order of
      recruitment of pairs of selected motor units was the same for each of the three
      tasks.

PMID- 7813688
TI  - A re-examination of the effects of instruction on the long-latency stretch reflex
      response of the flexor pollicis longus muscle.
AB  - We re-examined the issue of how a subject's intention to react to a joint
      perturbation may modulate the long-latency M2 stretch reflex response. The
      experiments were done on the flexor pollicis longus muscle (FPL) of the human
      thumb, for which there is evidence that its M2 reflex response is mediated, at
      least in part, by a pathway that traverses the motor cortex. The participation of
      the cerebral cortex in the genesis of the M2 reflex response may allow for a
      modulation of its amplitude, based on the intention of the subject. To test
      whether the M2 response is genuinely modulated by the subject's intention, we
      examined the magnitude of this response as a function of the FPL background level
      of activation, measured by the surface rectified and filtered EMG. The subject
      was instructed either to oppose the perturbation as quickly as possible, not to
      react, or to relax as quickly as possible after the onset of the perturbation.
      The time integral of the long latency FPL EMG response, computed between 40 and
      70 ms following the onset of stretch, was plotted against the mean torque
      produced by the distal inter-phalangeal joint of the thumb, or against the mean
      background FPL EMG. There were no significant differences in the FPL M2 EMG
      responses for different instructions. The amplitude of the reflex response was
      dependent only--in an approximately linear manner--on the background level of
      muscle activation. The total joint stiffness (intrinsic plus reflex) was also
      calculated for each combination of instruction and background torque.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7813689
TI  - A temporal-spatial cluster of sudden infant death syndrome in Navarre, Spain.
AB  - An apparent temporal-spatial cluster of Sudden Infant Death Syndrome (SIDS) was
      noted in the Autonomous Community of Navarre, Spain, when four unrelated children
      aged between 1 and 6 months died unexpectedly within a 7-day interval in January,
      1990. The population under one year of age in Navarre was approximately 4,800.
      The scan test of temporal clustering showed that the sudden infant deaths
      occurred closer to one another in time significantly more often than would be
      expected by chance. All four infants lived in a neighbourhood of the capital of
      Navarre, which accounts for approximately half the region's population. The
      clustered cases coincided with an outbreak of influenza type A detected by the
      epidemiological surveillance system and seen by the increase in 1990 over the
      same period in the previous year in the number of paediatric emergency-ward
      admissions during the 'epidemic' days. The results confirm the presence of a
      temporal-spatial cluster of SIDS and favour an environmental etiology where
      exposure to influenza A viruses is implicated.

PMID- 7813690
TI  - Knowledge, attitudes and beliefs of European injecting drug users concerning
      preventive measures for HIV.
AB  - Strategies for controlling the HIV epidemic include education and information
      campaigns for intravenous drug users (IDUs), as for all high-risk groups, and the
      provision of various public health measures and treatment. These can only be
      effective if the IDU is aware of them and has a favourable image of them. A study
      of 2330 IDUs in 12 European countries recorded awareness and opinions of various
      categories of measures and institutions. Of all measures, those mentioned most
      often related to availability of new injecting equipment; specifically
      unrestricted sales in pharmacies and needle exchanges, which were also thought to
      be more useful than anything else. Prompted awareness of rehabilitative
      institutions was well over 90% in most countries, but up to a quarter of IDUs did
      not trust them and up to one fifth did not think that they were useful. There
      appears to be a general need for more effective communication with IDUs to
      improve the image of the services available.

PMID- 7813692
TI  - Trends in blood pressure and the prevalence and treatment of hypertension in
      young adults in The Netherlands, 1974-1986.
AB  - To investigate trends in blood pressure and the prevalence and treatment of
      hypertension in the Netherlands between 1974 and 1986, data from two screening
      projects on cardiovascular risk factors were used. Between 1974 and 1980 about
      30,000 men and women aged 37-43 were screened. Between 1981-1986 about 80,000 men
      aged 33-37 were examined. An increase in average systolic blood pressure by 2
      mmHg in men in the period 1974-1980 was followed by an insignificant change
      during the period 1981-1986. Average diastolic blood pressure increased by 4 mmHg
      between 1974 and 1980 but decreased by the same amount between 1981 and 1986. The
      prevalence of hypertension in 40-year-old men increased from 12.7% in 1974 to
      17.8% in 1980. The prevalence of hypertension in 35-year-old men did not change
      between 1981 and 1986 and amounted to 9.6%. Treatment of 40-year-old hypertensive
      men increased from 8% in 1974 to 21% in 1980 and from 9% in 1981 to 13% in 1986
      among 35-year-old men. Average systolic blood pressure did not change in 40-year
      old women between 1974-1980 but average diastolic blood pressure increased by 2
      mmHg during that period. The percentage of hypertensive women was 8.5% and did
      not change between 1974 and 1980. Also, the percentage of treated hypertensive
      women did not change and amounted to 28%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7813691
TI  - Prevalence rates of gallstone disease in Italy. The Chianciano population study.
AB  - The prevalence of gallstone disease and associated factors in the entire
      population of subjects aged 15-65 years born and resident in Chianciano Terme
      (Siena - Tuscany) was examined in the years 1985 and 1986. The investigation
      included gallbladder ultrasonography, administration of a questionnaire on
      personal and family history, physical examination and blood chemistry. A total of
      1809 subjects (attendance rate 87.7%) participated in the study. Personal history
      and physical examination showed that Chianciano inhabitants have a low prevalence
      of obesity (4.3%) and only 4.4% of the female population had more than two
      pregnancies. Overall prevalence of gallstone disease
      (cholecystectomy+cholelithiasis) was 5.9% (3.7% for males and 8.4% for females).
      Age standardized relative risk of gallstone disease for females was 2.25 (95%
      confidence limits = 1.68-2.68). Prevalence of cholelithiasis was 3.5% (2.7% for
      males and 4.2% for females). Prevalence of gallstone disease increased with
      increasing age in both sexes, being extremely low in the age interval of 15-29
      years (0.25%). The overall gallstones/cholecystectomy ratio was found to be lower
      (1:1) in females than in males (2.7:1). Although subjects with gallstones
      reported more frequently biliary colics and non-specific dyspeptic symptoms, the
      diagnostic power of all symptoms in identifying cholelithiasis was very poor due
      to low sensitivity. Only one third of subjects with gallstones was aware of
      having the disease. Age, obesity and number of pregnancies were positively
      associated with gallstone disease in univariate analyses. The association with
      obesity and parity disappeared in multivariate analysis. Blood lipids and glucose
      were not associated with the disease both in univariate and multivariate
      analyses.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7813693
TI  - Hypertension prevalence and age-related changes of blood-pressure in semi-nomadic
      and urban Oromos of Ethiopia.
AB  - We evaluated the prevalence of hypertension and the age-related behaviour of
      systolic blood pressure (SBP) and diastolic blood pressure (DBP) in a wide sample
      of male and female Ethiopian Oromos living in rural or pre-industrial urbanized
      settings. Blood pressure (BP) was measured in the sitting position after 5 min
      rest in 5277 Oromos. In the group, 4928 were semi-nomadic shepherds, while 349
      came from a town of 60,000 inhabitants where they were involved in low-technology
      jobs. The first subgroup was composed of 2482 men and 2446 women. All subjects
      were divided into 3 age groups: 15-44, 45-64, and > or = 65 years. Body weight
      (BW) and the Quetelet index (QI) were matched to BP levels using Pearson's
      method. In semi-nomadic men, SBP was 121.4 +/- 8.4 mmHg versus 132.4 +/- 10.4
      mmHg in urban men (p < 0.001). In women, SBP was 120.5 +/- 7.9 mmHg versus 128.1
      +/- 10.1 mmHg (p < 0.001). The prevalence of hypertension was 0.40% in the semi
      nomadic and 3.15% in the urban population. In the latter, significant increases
      in BW and QI were found, which were significantly correlated to both SBP and DBP.
      In semi-nomadic men, a 5.33% increase in SBP and a 5.22% in DBP was found between
      age groups 1 and 2 (p < 0.001 in both). In urban men the increase was 4.77% and
      3.41% respectively (p < 0.001). In both male populations no difference in SBP and
      DBP was observed between age groups 2 and 3.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7813694
TI  - HTLV-I and HTLV-II infections among HIV-1 seropositive patients in Sao Paulo,
      Brazil.
AB  - To estimate the presence of, and the risk factors for HTLV-I and HTLV-II
      infections among HIV-1 infected subjects in Sao Paulo, Brazil, a serosurvey was
      performed in 471 HIV-1 infected patients, including 216 intravenous drug addicts
      (IVDA), 229 homosexual/bisexual men, and 26 with other risk factors. Serum
      samples were screened for HTLV seroreactivity by ELISA; reactive samples were
      analyzed by Western Blot (WB), using whole HTLV-I lysate as antigen. To confirm
      and discriminate HTLV-I and HTLV-II infections, sera presenting any bands on WB
      were further analyzed by a WB containing recombinant HTLV-I and HTLV-II proteins
      (WB 2.3), and by enzyme immunoassays using synthetic peptides specific for
      envelope proteins (Synth-EIA). In 22 cases, cell samples were available for
      polymerase chain reaction (PCR) studies. On WB, 114 sera were reactive and, of
      these, 37 and 25 were concordantly positive on both WB 2.3 and Synth-EIA
      procedures for HTLV-I and HTLV-II specific antibodies, respectively; 37 specimens
      were negative on both assays, and 15 gave discordant or indeterminate results.
      PCR findings confirmed concordant results obtained in the discriminatory
      serological assays. The prevalence rates of HTLV-I and HTLV-II infections were
      15.3% and 11.1% in IVDA, and 0.9% and 0.4% in homosexual/bisexual men,
      respectively. No case of HTLV-I/HTLV-II co-infection was found.

PMID- 7813695
TI  - Survey on the prevalence of leptospira infections in the Italian population.
AB  - This investigation is the first nationwide survey on the circulation of
      leptospira infections in human beings in Italy. In nine out of twenty Italian
      regions, representative samples of the population were investigated for the
      presence of leptospira infections. Unexpectedly, leptospira infections were found
      to be widespread, the number of cases being much higher than the diagnosed
      clinical cases. There were found to be high, medium, and low risk areas. On the
      whole, the risk for the rural population was no higher than the risk for urban
      dwellers; leisure activities, contact with animals and residence on the plain
      versus residence in the hills were important risk factors. There was an
      unidentified risk factor in urbanites which was absent in the rural population. A
      changing pattern in infecting serovars was observed, with infections from
      serogroups Sejroe, Javanica and Australis prevailing over infections from the
      Icterohaemorrhagiae and Bataviae serogroups, which were the main agents of human
      leptospirosis during the 1950s. The mechanisms of these changes, the need for
      epidemiological surveys and improved diagnostic methods of screening are
      discussed.

PMID- 7813696
TI  - The role of life events in different categories of preterm birth in a group of
      women with previous poor pregnancy outcome.
AB  - The aim of the present study was to determine whether mothers reporting more life
      events experience more preterm births following both complicated and
      uncomplicated pregnancies. A Life Events Inventory was administered prospectively
      to women at high risk for poor obstetric and neonatal outcomes who took part in
      the Pregnancy Home Visiting Program (PHVP), a randomized controlled trial of the
      effect of a programme of antenatal home visits by midwives on the incidence of
      preterm birth. This study took place in Western Australia in the years 1984-1987.
      All women in the study had had a previous poor pregnancy outcome. The women were
      classified into two groups--those with complicated and those with uncomplicated
      pregnancies. Pregnancies classified as 'complicated' were defined as a pregnancy
      in which there was antenatal hospital admission(s) for hypertension, antepartum
      haemorrhage or other medical reason except for preterm birth. Pregnancies
      classified as 'uncomplicated' refer to all pregnancies without these
      complications. No significant association was found between life events and
      preterm birth although the total stress score for women with uncomplicated
      pregnancies almost reached significance, as did the number of life events for
      both women with complicated and women with uncomplicated pregnancies considered
      together. Life events were not shown to have a predictive relationship to preterm
      birth even when stratified by etiologically different groups. However, although
      stress was not an important predictor of preterm birth in this group of women at
      biological risk it may yet be so in a group at social risk.

PMID- 7813697
TI  - Demonstration of HCV-RNA and HBV-DNA in the serum of HBsAg negative patients with
      hepatocellular carcinoma.
AB  - Forty patients with chronic liver disease and HCC were analyzed for infection
      with hepatitis C (HCV) and hepatitis B (HBV) viruses. All patients were negative
      for HBsAg, 16 were alcoholics, 6 had previous blood transfusions and 18 had
      sporadic chronic hepatitis. Antibodies to HCV were determined by EIA 2nd
      generation. HBV-DNA was detected by PCR using primers of the precore region.
      Analysis of HCV-RNA was done with nested PCR amplifying the 5' non-coding region
      of the HCV genome, using primers complementary to nucleotides 1-20 and 305-320
      and nested primers complementary to nucleotides 21-31 and 271-286 of the HCV-J1.
      Anti-HCV were positive in 35/40 patients (87.5%). HCV-RNA was detected by PCR in
      34 patients (85%) all of them positive for the anti-HCV. HCV-RNA was detected in
      70.5% of the alcohol abusers, in 100% of patients with history of transfusion(s)
      and 94.1% of patients with cryptogenic chronic liver disease. HBV-DNA was
      detected in only 2 patients. In conclusion, there is a high rate of HCV and a low
      rate of HBV viremia detected by PCR in Spanish patients with HCC HBsAg negative.
      No patient without anti-HCV presents HCV-RNA. Our results suggest that persistent
      HCV replication may play a role in hepatic carcinogenesis, as HBV-DNA could be
      found in only 5% of our HCC patients.

PMID- 7813698
TI  - What the experts think: a European survey of expert opinion about the influence
      of lifestyle on health.
AB  - This paper describes an assessment of expert medical and epidemiological opinion
      about the role of lifestyle in health, carried out by means of a questionnaire
      survey of senior members of academic departments of public health, epidemiology
      and social medicine in Western European universities. Estimates were made of the
      influence of eight lifestyle factors--smoking, alcohol consumption, exercise,
      stress, body weight, dietary fat, fibre and salt--on the aetiology or course of
      five disorders: heart disease, high blood pressure, lung cancer, breast cancer
      and diabetes. One hundred and fifty responses were received from scientists and
      clinicians from 16 countries. Respondents had an average of 17.8 years experience
      in their discipline (range 5-40 years). The only links to be endorsed as definite
      by over 90% of respondents were those between smoking and both heart disease and
      lung cancer. However, more than 70% considered alcohol consumption, exercise,
      stress body weight and dietary fat to be definite or probable influences on heart
      disease. Smoking, alcohol, exercise, stress, body weight and salt intake were
      endorsed as relevant to high blood pressure by more than 70%. Opinions differed
      widely about the influence of lifestyle on breast cancer and diabetes. Experts
      from the United Kingdom and Republic of Ireland were less positive than
      respondents from other countries about the influence of stress, dietary fat,
      fibre and salt on disease. The results indicate that comparatively few lifestyle
      factors were believed to be unequivocally related to any of the five disorders.
      Experts from the UK and Ireland were generally les likely to endorse lifestyle
      disease links than those from other European countries.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7813699
TI  - Association of alcohol consumption and Helicobacter pylori infection in young
      adulthood and early middle age among patients with gastric complaints. A case
      control study on Finnish conscripts, officers and other military personnel.
AB  - There is growing evidence that Helicobacter pylori is responsible for a variety
      of gastric and duodenal changes which can eventually lead to stomach cancer.
      Little is known about risk factors for H. pylori infection. We re-analyzed the
      association of alcohol with H. pylori positivity in 451 conscripts, officers and
      other military personnel endoscoped due to gastric complaints in the Central
      Military Hospital of Finland in 1987 and 1988. Serology and culture were done in
      all patients. Alcohol consumption histories were obtained by use of a self
      administered questionnaire. We observed a high odds ratio (OR) of H. pylori
      infection among young adults who were heavy alcohol consumers compared to non
      drinkers (OR 5.32, 95% confidence interval: 1.09-25.95). There was evidence of a
      dose response when heavy and moderate drinkers were compared to non-drinkers
      (Mantel-Haenszel chi 2 for trend, p = 0.02) in young adulthood. A subgroup of
      young respondents who reported drinking all classes of alcohol (including hard
      liquor) showed an even stronger association and more significant dose-response.
      Multivariate techniques revealed a qualitative interaction of alcohol with H.
      pylori positivity in different age groups and among old people an inverse
      association of H. pylori and alcohol consumption was observed. These findings, if
      confirmed independently, might have implications for preventing a variety of
      gastric and duodenal lesions, since they allow identification of high risk
      groups.

PMID- 7813700
TI  - Cancer mortality of family members of patients with chronic lymphocytic leukemia.
AB  - A case-control study comprised 130 cases affected by chronic lymphocytic leukemia
      and the same number of individually matched controls, with accidental injuries as
      a cause of hospitalization. Matching criteria were: sex, age, type of settlement,
      and area of residence. Both leukemias and all cancers were more frequent among
      family members of cases, as compared to controls.

PMID- 7813701
TI  - Cryptosporidium oocysts in water for human consumption. Comparison of staining
      methods.
AB  - A study was carried out on the presence of oocysts of Cryptosporidium spp. in
      water for human consumption in the Province of Salamanca, Spain, using four
      different staining techniques: Ziehl-Neelsen, auramine, indirect
      immunofluorescence with monoclonal antibodies (Meridian, USA) and direct
      immunofluorescence with monoclonal antibodies (Pasteur, France). The presence of
      oocysts was detected in the water used for the washing of sand filters in the
      four water purifying plants and in the drinking water of two of the six
      geographical areas studied. The Ziehl-Neelsen and auramine staining techniques
      were found to have excellent diagnostic correlation. Immunofluorescence stainings
      with monoclonal antibodies proved to be less sensitive.

PMID- 7813702
TI  - Hepatitis B in children in Italy: incidence and risk factors: SEIEVA
      Collaborating Group. Sistema Epidemiologico Integrato dell'Epatite virale Acuta.
AB  - The objectives of the present report were to give a baseline picture of hepatitis
      B notification incidence rates in children before the campaign of mass
      vaccination for newborns and adolescents (12-13 years old), and to study the role
      of different risk factors. Data from a specific national surveillance system of
      acute viral hepatitis (SEIEVA, Sistema Epidemiologico Integrato dell'Epatite
      Virale Acuta) were used and acute hepatitis B cases were compared to acute
      hepatitis A patients with the case-control study method to estimate the
      associations with the considered risk factors. Since the system began, one
      hundred and sixty-three local health departments have joined SEIEVA covering 30%
      of the Italian population. The incidence of acute hepatitis B notifications among
      0-14 aged children was 9 per 100,000 in 1985 and 1 per 100,000 in 1990. Such
      decline in incidence was observed in both the North and the South of Italy.
      Surgical interventions, dental therapy and household contacts with a HBsAg
      chronic carrier were found to be associated with acute hepatitis B. The point
      estimate of the odds ratio was 10 for the latter risk factor. Other preventive
      measures in addition to vaccination are needed to control the risk of hepatitis B
      infection and other parenteral diseases due to surgical intervention and dental
      therapy.

PMID- 7813703
TI  - Helicobacter pylori infection and gastritis in healthy Nigerians.
AB  - In a study of forty asymptomatic volunteers from northern Nigeria; 35 (87.5%) had
      histological gastritis and 32 (80%) were infected by Helicobacter pylori. All but
      one of the patients infected by Helicobacter Pylori had histological gastritis.
      This high prevalence of H. Pylori infection in young, asymptomatic subjects,
      occurs in an area with a low prevalence of duodenal ulcer. The possible reasons
      for this are discussed.

PMID- 7813704
TI  - Characterization and protective effect of a 29 kDa protein isolated from Coxiella
      burnetii by detergent Empigen BB.
AB  - A 29 kDa protein, isolated from the outer membrane of Coxiella burnetii, strain
      Nine Mile phase I by detergent Empigen BB, was characterized. The failure in
      removing lipopolysaccharides (LPS) from preparations of the protein by the
      purification method used indicates a strong binding between proteins and LPS in
      the outer membrane of C. burnetii. The protein was immunogenic in mice and
      protected them against virulent C. burnetii challenge.

PMID- 7813706
TI  - Effect of recombinant human erythropoietin on platelets in patients with anemia
      of renal failure: correlation of platelet count with erythropoietic activity and
      iron parameters.
AB  - We examined the effect of treatment with rHuEpo on platelet counts in 61
      hemodialysis patients and correlated them with changes in erythropoietic
      activity, iron status and inflammation. Platelets (10(9)/1) increased from 220 +/
      80 to 245 +/- 102 after 14 days and stabilized at that level up to day 90 (p <
      0.0001). The increment was similar in complete or partial responders but was not
      observed in failures. Serum transferrin receptor (sTfR, a measure of total
      erythropoiesis) and Het rose much more progressively, but relative platelet
      increments correlated with relative increases in sTfR and Hct. Relative platelet
      increments correlated inversely with relative changes of SeFe or transferrin
      saturation, but not with their absolute values, nor with baseline ferritin or its
      progressive decrease. Although baseline platelet count was 12% higher in patients
      with inflammation and correlated with serum haptoglobin, relative increases were
      similar in patients with or without inflammation. In conclusion, rHuEpo produced
      a clinically minor but consistent elevation of platelet counts. These
      modifications were not related primarily to modifications in iron stores,
      functional iron deficiency, or inflammation, but paralleled the expansion of
      erythropoietic activity. The results suggest that rHuEpo has a small positive
      effect on platelet production, but it cannot be ruled out that this could be
      partially mediated through functional iron deficiency.

PMID- 7813705
TI  - Crohn's disease in the Kinneret sub-district, Israel, 1960-1990. Incidence and
      prevalence in different ethnic subgroups.
AB  - Crohn's disease has been predominant in Jewish patients in some countries (USA,
      UK, Sweden). The purposes of this study were: to continue to map the morbidity in
      Israel and the trends of the rate over time. The mean annual incidence rate in
      the Kinneret sub-district among Jews was 1.96/100,000 during 1960-1990 and
      2.98/100,000 in the last decade. The prevalence rate in 1990 among Jews was
      45.9/100,000 and was twofold among European-American-born compared to other
      ethnic groups. No cases were found among Arabs, although they make up about 25%
      of the area's population. The conclusions are: (1) morbidity rate of Crohn's
      disease increased over time, and (2) in the last decade incidence rates among
      Jews of Asian-African origin are similar to, or even higher than those of
      European-American origin.

PMID- 7813707
TI  - Clonal T-lymphocytes from untreated hairy-cell leukaemia patients enhance the
      growth of BFU-E.
AB  - The anaemia in hairy cell leukaemia (HCL) has been suggested to be mediated in
      part by T lymphocytes. Consequently, we have investigated the role of T
      lymphocytes in this disease by cloning pre-treatment HCL T lymphocytes and
      testing their influence on the in vitro growth of BFU-E from autologous post
      treatment and normal donors T-lymphocyte depleted peripheral blood mononuclear
      cells (PBMNC-T). Altogether, 24 CD4+/CD8- and 17 CD4-/CD8+ T-lymphocyte clones
      from 3 different HCL patients were tested. All were found to enhance the growth
      of BFU-E, the degree of enhancement being independent of the length of IFN
      treatment at the time of the post-treatment sampling. Likewise, no difference in
      the extent of enhancement was seen between CD4+/CD8- and CD4-/CD8+ clones, or
      whether the clones were tested for modulation of BFU-E from PBMNC-T of autologous
      or allogeneic origin. Finally, no differences could be observed between different
      patients in the extent of clonal enhancement. These findings, which are in line
      with our previous ones in normal donors, indicate that the T-lymphocyte function
      with regard to regulation of the erythropoiesis is normal in HCL, arguing against
      a T-lymphocyte mediated suppression of the erythropoiesis in HCL.

PMID- 7813708
TI  - Life expectancy in primary myelodysplastic syndromes: a prognostic score based
      upon histopathology from bone marrow biopsies of 569 patients.
AB  - The retrospective evaluation of bone marrow biopsies of 569 patients with primary
      myelodysplastic syndrome--pMDS--revealed 256 refractory anemias--RA--, 52
      refractory anemias with ringed sideroblasts--RARS--, 133 refractory anemias with
      excess of blasts--RAEB--, 52 refractory anemias with excess of blasts in
      transformation--RAEB-t--, and 53 chronic myelo-monocytic leukemias--CMMOL-
      according to FAB-criteria, 23 patients were not otherwise specified
      (myelodysplastic syndrome: not otherwise specified--MDS.NOS--). RARS-patients had
      the best prognosis (median survival 41.9 months, incidence of leukemia 3.8%),
      followed by RA-patients (26.5 months, 16.4%), MDS.NOS-patients (22.4 months,
      21.7%), CMMOL-patients (12.5 months, 49.1%). RAEB- and RAEB-t-patients had the
      worst prognosis (median survival time 8.5 and 4.6 months, incidence of leukemia
      42.1% and 57.7%, respectively). But the survival times showed a considerable
      range in each FAB-subgroup with 0-154 months in RA or 0-52 months in CMMOL. To
      forecast life expectancy more precisely, a scoring system was developed using
      nine histopathological parameters, among which the three most important ones were
      determined: quantity of myeloblasts, myelofibrosis and ALIP's. The scoring system
      allows a determination of three risk groups with significantly different survival
      times. It is valid also for patients without increase of myeloblasts (< 5%
      myeloblasts in the bone marrow) and identifies high-risk MDS patients in this
      group. By this proposed scoring system, a prognostic approval in primary MDS can
      be achieved applying histopathology without regarding further methods herewith
      presenting a system which could be considered independently from hematologic,
      cytological or laboratory data.

PMID- 7813709
TI  - Lineage involvement and karyotype in a patient with myelodysplasia and blood
      basophilia.
AB  - We report a 63-year-old woman with myelodysplastic syndrome (MDS), refractory
      anaemia with ring sideroblasts (RARS), and blood basophilia with pathological
      forms. Karyotype analysis revealed a complex rearrangement:
      46,XX,del(3)(p13p25),del(5)(q13q33),der(16)t(1;16)
      (p13;q12)/47,idem,add(20)(?p11)/49,idem, + add(1)(q32),add(20)(?p11), +
      mar/46,XX. Karyotype, immunophenotype and in situ hybridization studies by the
      MAC (morphology antibody chromosomes) combination technique revealed the
      chromosomal abnormality in granulocytic/monocytic and erythrocytic metaphase
      cells. Also mature basophils and other granulocytes were involved with the
      abnormality. We suggest that our patient with the MDS has a stem cell disorder
      affecting all myeloid cell lineages and that basophilia constitutes a part of the
      malignant process.

PMID- 7813711
TI  - Polymyositis in a myeloproliferative disorder.

PMID- 7813710
TI  - Deferiprone-associated myelotoxicity.
AB  - Agranulocytosis developed in a 63-year-old patient with myelodysplasia 6 weeks
      after commencing treatment with the oral iron chelator deferiprone (L1, 1,2
      dimethyl-3-hydroxypyrid-4-one, CP20) at a daily dose of 79 mg/kg. This was the
      3rd case of agranulocytosis (neutrophils 0 x 10(9)/l) in clinical trials of L1 at
      the Royal Free Hospital. The neutrophil count recovered 7 days after stopping L1
      and commencing G-CSF at a dose of 300 micrograms daily. Three other patients with
      milder degrees of neutropenia (neutrophils < 1.5 x 10(9)/l) have also been
      observed in our trials. The case histories of these 4 patients are described
      here; other reported cases of neutropenia or agranulocytosis are reviewed. Based
      on worldwide long-term clinical trials the incidence of agranulocytosis is about
      1.6% and of neutropenia 2%.

PMID- 7813712
TI  - Cutaneous infiltration by histiocytic lymphoma in a patient with acute monocytic
      leukemia (M5a)

PMID- 7813713
TI  - Emergence of mouse erythrocyte receptor, CD21, CD23, and PCA-1 in hairy cells
      during deoxycorformycin therapy.

PMID- 7813714
TI  - Dual energy X-ray absorptiometry measurements of bone mineral density in myeloma.

PMID- 7813715
TI  - The early years of vascular surgery in The Netherlands (1950-1965).

PMID- 7813716
TI  - Coatings for vascular prostheses: mesothelial cells express specific markers for
      muscle cells and have biological activity similar to that of endothelial cells.
AB  - The use of human omentum as an alternative to veins as a source of cells for
      seeding onto small-caliber vascular prostheses has awakened controversy as to the
      identification of the predominant cell type derived from this source. Mesothelial
      cells from omentum were extracted by collagenase digestion, and cultured until a
      monolayer was formed. These cells showed positivity for monoclonal antibodies
      specific for endothelial cells (anti-CD34 QBEND10), antibodies to intermediate
      filaments (anti-vimentin and anti-desmin) and anti-smooth muscle cell antibodies
      (anti-actin and anti-total actin). The mesothelial cells behaved like endothelial
      cells derived from vein when seeded onto polytetrafluoroethylene prostheses,
      showing high levels of prostacyclin production. This report provides additional
      evidence of the non-endothelial origin of the cells derived from human omentum.

PMID- 7813717
TI  - Direct evidence of free radical production after ischaemia and reperfusion and
      protective effect of desferrioxamine: ESR and vitamin E studies.
AB  - After surgical renal revascularisation, warm renal ischaemia due to renal artery
      cross-clamping contributes to postoperative renal dysfunction. After reperfusion,
      free radicals are thought to be a significant cause of injury. Nevertheless,
      indisputable proof of free radical production is scarce, partly because of their
      transient nature. In this study, electron paramagnetic resonance and vitamin E
      levels were used to demonstrate the free radical production after renal ischaemia
      and reperfusion. Rabbit kidneys were submitted either to 15 or 60 minutes of
      ischaemia followed by reperfusion. A spin trap agent (alpha-phenyl-N-tert-butyl
      nitrone (PBN), 20mg/ml, 1 ml/min) was infused during reperfusion directly into
      the left renal artery via an aortic catheter before declamping. Blood samples
      were selectively drawn from the left renal vein for ESR analysis (Varian
      spectrometer E109) of lipidic residues extracted from blood samples. The vitamin
      E content of the left renal cortex was determined by HPLC procedure. The right
      renal cortex was used as a control for the vitamin E values. In the venous
      effluent, ESR analysis revealed the formation of a spectrum consisting of a
      triplet of asymmetric doublets. This signal resulted from the spin trapping by
      PBN of a mixture of both oxygen- and carbon- centred lipidic radicals. The
      amplitude of the signal which is proportional to the amount of free radicals was
      significantly higher after 60 minutes ischaemia than after 15 minutes.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7813718
TI  - Spiral CT-angiography of the aorta.
AB  - AIMS: To determine whether the new technique of CT-angiography was accurate in
      displaying the complex anatomy of the aorta and its major branches. METHODS:
      Seventeen patients with a variety of aortic pathology were examined. Using a
      spiral CT-scanner a volumetric scan was made during injection of 150 cc of i.v.
      contrast. Depending on the chosen CT technique, a body volume with a length
      ranging between 25-100 cm could be examined in one 50 second spiral scan. On the
      resulting transverse slices vascular lumina and extent of thrombus were studied.
      Subsequently, the transverse slices were reconstructed in the coronal or sagittal
      plane in order to appreciate the craniocaudal relations of the vascular anatomy.
      Finally, three-dimensional reconstructions were made of vascular lumina and
      thrombus. RESULTS: In aortic aneurysms the extent of the aneurysmal dilatation
      and of the adherent thrombus could be accurately located relative to the origins
      of renal and visceral branches proximally, and iliac bifurcation distally. In
      cases of severe elongation, dissection or complex anatomy, a detailed
      preoperative insight into the individual anatomy could be obtained. The two
      dimensional axial and multiplanar reconstructions offered excellent anatomic
      detail. The three-dimensional reconstructions, being based on a considerable data
      reduction, offered an efficient means of providing an overall view of complex
      anatomic relations. CONCLUSION: The advantage of CT-angiography is that, based on
      a single spiral scan, the vascular structures in the examined body volume can be
      displayed in any desired plane using multiplanar reconstructions. Alternatively,
      three-dimensional renderings can be created. The combination of multiplanar
      reconstructions and three-dimensional reconstructions makes CT-angiography an
      accurate technique for displaying even the most complex aortic anatomy.

PMID- 7813720
TI  - Intraoperative imaging techniques in infrainguinal arterial bypass grafting:
      completion angiography versus vascular endoscopy.
AB  - This prospective study was designed to establish whether vascular endoscopy would
      provide more information on the graft lumen than standard completion angiography
      during infrainguinal bypass surgery. Ninety-nine patients with 102 infragenicular
      bypass grafts who underwent both angiography and angioscopy intraoperatively were
      evaluated. In 99 of the 102 patients the indication was critical limb ischaemia.
      Of the 102 bypass grafts, 81 were autogenous vein. Distally, 24 grafts were
      anastomosed to the below-knee popliteal segment, 64 extended to the crural and 14
      to the pedal arteries. On completion of the distal anastomosis, grafts were first
      evaluated by angiography and then by angioscopy. The images obtained with the two
      monitoring modalities were compared by the operating surgeon and re-explorations
      were performed immediately if necessary. Completion angiography and angioscopy
      produced images of good quality in 96 and 97 cases, respectively. In 12 cases
      completion angiography showed abnormalities. Of these, five were located below
      the distal anastomosis and were not accessible to angioscopic examination.
      Conduit defects were found in seven instances. In one of them angioscopy showed
      the angiogram to be false-positive. Of the 90 grafts with normal completion
      angiograms, seven were found to show significant pathology on angioscopy.
      Compared to angioscopy, the sensitivity and specificity of angiography to detect
      abnormalities within the graft was 46% and 98%, respectively. Our results suggest
      that vascular endoscopy is superior to angiography for disclosing conduit
      defects, but that it does not provide adequate information about the distal
      arterial anatomy.

PMID- 7813719
TI  - Tomographic cerebral blood flow measurement during carotid surgery.
AB  - OBJECTIVES: The aim of the study was to depict regional cerebral blood flow
      (rCBF) during carotid cross clamping using 99mTechnetium-hexamethylpropylene
      amine oxime (TcHMPAO). This tracer rapidly passes the blood-brain barrier and is
      retained for hours in the brain tissue. Injecting TcHMPAO during surgery and
      performing single photon emission computer tomography (SPECT) scanning shortly
      after the operation thereby pictures rCBF at the time of injection. DESIGN:
      Ongoing prospective study. SETTINGS: Departments of Vascular Surgery, Neurology
      and Anaesthesiology, University Hospital, Rigshospitalet, Copenhagen, Denmark.
      MATERIAL: 15 patients who during a period of 4 months underwent carotid
      endarterectomy. CHIEF OUTCOME MEASURES: Prior to surgery rCBF was determined
      using 133Xe and SPECT. Intraoperatively stump pressure was measured and a bolus
      of TcHMPAO was injected for later SPECT measurement. MAIN RESULTS: We found a
      significant correlation between stump pressure and enhancement of side-to-side
      asymmetry in rCBF due to carotid cross clamping. Pronounced variations were seen
      in which regions were deprived of perfusion during clamping. CONCLUSION: TcHMPAO
      allows tomographic assessment of CBF during carotid surgery. This method may
      serve as a reference tool in future research on intraoperative cerebral
      haemodynamics.

PMID- 7813721
TI  - Magnetic resonance angiography or IADSA for diagnosis of carotid pseudo
      occlusion?
AB  - Accurate diagnosis of internal carotid artery (ICA) occlusion is essential in the
      investigation of carotid disease yet may be difficult using Duplex. Traditionally
      contrast arteriography has been used to confirm the diagnosis despite its cost
      and potential dangers. Twenty-one patients with 23 ICA occlusions were evaluated
      by a 3-dimensional time of flight magnetic resonance angiography (MRA) technique.
      The cervical carotids and circle of Willis were imaged during the MRA examination
      which lasted 30 minutes. Confirmatory conventional angiography was performed in
      all patients. Using angiography as the gold standard, all occlusions were
      correctly diagnosed by MRA and 22 of 23 occlusions correctly diagnosed by Duplex.
      There was good agreement between MRA and angiography for all 42 ICAs imaged
      (Kappa statistic 0.83). Diagnosis of internal carotid artery occlusion is
      critical as it determines the need for operation. In this situation MRA provides
      a useful non-invasive complement to Duplex. A combination of non-invasive studies
      may enable arteriography to be rejected with greater confidence in this high risk
      group.

PMID- 7813722
TI  - Raynaud's phenomenon and cold stress testing: a new approach.
AB  - There are a number of methods of evaluating digital blood flow in the vascular
      laboratory but none fulfills the criteria of providing a quick and reproducible
      diagnostic test for Raynaud's phenomenon. We present our experience with the use
      of high frequency ultrasound to provide direct real time imaging of the digital
      arteries. Using this method and a standardised cold challenge test, consisting of
      exposure of the hand to a temperature of 10 degrees C for 5 minutes, it is
      possible to distinguish patients with Raynaud's phenomenon from normal controls
      on the basis of extent of digital artery closure. The mean fall in digital artery
      diameter on cold challenge, expressed as a percentage of the original diameter,
      was 92.4% (S.D. = 16.4, S.E.M. = 2.1) in patients with Raynaud's phenomenon as
      against 8.7% (S.D. = 11.5, S.E.M. = 2.5) in a group of normal volunteers. Using a
      45% fall in digital artery diameter as the diagnostic cut-off point, the test has
      a specificity of 100% and a sensitivity of 96.6% in differentiating patients with
      Raynaud's phenomenon from controls. It is suggested that the test could be used
      as objective confirmation of a clinical diagnosis and to assess the efficacy of
      therapeutic interventions.

PMID- 7813723
TI  - Time-related anticoagulation after regional and systemic administration of
      heparin in patients undergoing aortoiliac surgery.
AB  - Heparin anticoagulation during cardiovascular surgical procedures remains poorly
      investigated and understood. The objective of this investigation was to assess
      the effectiveness of three methods of heparin administration. Heparin sulfate (75
      IU/kg) administered to patients undergoing aortoiliac surgery was randomised to
      one of three methods: Group I (n = 9) heparin was injected into a central venous
      line 5 minutes before infrarenal aortic clamping; Group II (n = 9) heparin was
      injected into the distal aneurysm immediately after infrarenal aortic clamping;
      and Group III (n = 8) heparin was injected into a central venous line immediately
      after infrarenal aortic clamping. Blood samples were analysed for anticoagulant
      activity from both the upper and lower extremities at 5, 15, 30, 60, and 120
      minutes after heparin administration. Anticoagulation, as measured by aPTT,
      antifactor Xa levels, and ACT, was achieved in all three groups by 5 minutes, but
      initially with lower heparin activity (measured as antifactor Xa) in the upper
      extremity (Group II) and lower extremity (Group III), respectively. These
      differences were also evident in ACT and aPTT determinations. Intravenous heparin
      administration prior to aortic cross-clamping achieves excellent anticoagulation
      (anti-factor Xa approximately 1 U/ml) in both upper and lower extremities after 5
      minutes. With regional administration, rapid heparin redistribution occurs, but
      it takes longer to achieve the same level of anticoagulation distant from the
      site of administration. Nevertheless, from a practical perspective the method of
      administration does not appear to have a great influence on the eventual
      achievement of adequate anticoagulation.

PMID- 7813724
TI  - Perioperative outcome of acute lower limb ischaemia on the basis of the national
      vascular registry. The Finnvasc Study Group.
AB  - OBJECTIVES: To determine the mortality and limb salvage rate in acute lower limb
      ischaemia and compare the risk factors and outcome after acute embolic and
      thrombotic peripheral arterial occlusion. DESIGN: Retrospective, multicentre
      clinical study. SETTING: 24 Departments of Surgery in Finland. MATERIALS: 509
      patients treated for acute lower limb ischaemia 1991-1992 as recorded in the
      Finnish national vascular registry (FINNVASC). CHIEF OUTCOME MEASURES: Major
      amputation and death. MAIN RESULTS: Previous major amputation or vascular surgery
      and smoking were found to be risk factors in patients with acute thrombosis (p <
      0.001). The overall amputation rate was 16% during the postoperative period. The
      amputation rate in patients with acute thrombosis was 26% and in those with
      embolism 10% (p < 0.001). Overall mortality was 13%, in patients with thrombosis
      16% and 11% in patients with embolism (p = 0.07). In a separate analysis of
      patients with acute thrombosis, major amputation was more common after
      thromboembolectomy than after reconstruction (p = 0.007). CONCLUSION: The rate of
      major amputations and mortality were higher in acute thrombosis. The high
      amputation rate in this group was particularly associated with the need for
      reoperations and thromboembolectomy rather than reconstruction.

PMID- 7813726
TI  - The assessment of cerebral oxygenation during carotid endarterectomy utilising
      near infrared spectroscopy.
AB  - Near infrared spectroscopy is a non-invasive method for continuous monitoring of
      tissue oxygenation. In 11 patients undergoing unilateral carotid endarterectomy,
      changes in cerebral oxygenation following carotid cross-clamping and declamping
      detected by a near infrared spectrometer were compared with corresponding changes
      in ipsilateral middle cerebral artery flow velocity measured by transcranial
      Doppler ultrasonography. Spectroscopic traces were obtained in all patients but
      adequate Doppler signals in only eight. Changes in cerebral haemoglobin
      oxygenation correlated closely (r = 0.908, p < 0.001) with changes in middle
      cerebral artery velocity. The near infrared spectrometer was also sensitive to
      the changes in cerebral haemodynamics due to intraoperative hypo- and
      hypertensive episodes. No evidence of cerebral intracellular hypoxia was seen and
      all patients made an uneventful recovery. Near infrared spectroscopy compares
      well with transcranial Doppler ultrasound as a monitor of cerebral function
      during carotid endarterectomy and may have a future role in the elucidation of
      cerebral perfusion and oxygenation changes following surgery.

PMID- 7813725
TI  - Recurrent pulmonary embolism in patients treated because of acute venous
      thromboembolism: a prospective study.
AB  - OBJECTIVE: To evaluate the risk of pulmonary embolism (PE) despite adequate
      heparin therapy in a large series of patients with acute deep venous thrombosis
      and/or pulmonary embolism. DESIGN: Prospective study. SETTING: University
      Hospital Germans Trias i Pujol, Badalona, Spain. MATERIALS: 348 patients admitted
      because of deep venous thrombosis in the lower limbs and/or pulmonary embolism. A
      baseline lung scan was obtained initially in every patient, whether the original
      diagnosis was PE or deep vein thrombosis (DVT). Repeat chest X-ray and lung scans
      were obtained routinely at 8 days of heparin onset. OUTCOME MEASURES: The primary
      trial endpoint was a finding of confirmed, clinically apparent recurrent PE; in
      addition, laboratory evidence of subclinical PE at the repeat scan was also
      considered. RESULTS: PE recurrences were found in 23/348 patients (7%). No
      significant differences were found in age and sex distribution, or in the degree
      of DVT proximity between patients who developed and those who did not develop
      recurrences. Recurrent PE was more commonly found in patients with scintigraphic
      evidence of PE on admission, irrespectively of the original diagnosis being DVT
      or PE (18/151 vs. 3/155; p = 0.0005, Fisher's exact test). Recurrences were also
      more common in patients in whom thrombosis developed in the absence of any known
      risk factor (10/70 vs. 13/278; p = 0.007). The logistic regression analysis
      confirmed the statistical significance of these two clinical variables.
      CONCLUSIONS: Pulmonary embolism despite adequate heparin therapy is not an
      uncommon event. It appears possible to identify a subgroup of patients at a
      higher risk, and, modify treatment accordingly.

PMID- 7813727
TI  - Abnormal mechanical properties of the aorta in Marfan's syndrome.
AB  - OBJECTIVES: Aortic dilatation, dissection and rupture are among the major causes
      of death in subjects with Marfan's syndrome. The aim of the study was to
      investigate the mechanical properties or compliance of the aorta in these
      subjects and compare them with a healthy age- and sex-matched reference
      population. MATERIALS AND METHODS: An ultrasound phase-locked echo-tracking
      system was used to determine diameter and pulsatile diameter change of the
      infrarenal aorta in nine subjects with Marfan's syndrome which were then compared
      with the values for 165 healthy individuals. Compliance, defined as the inverse
      of Ep (pressure strain elastic modulus) or stiffness (beta), was calculated from
      pulsatile diameter change and blood pressure obtained by the auscultatory method
      with a sphygmomanometer. For statistical analysis confidence intervals (95%)
      obtained from the healthy controls were used for comparison. Analysis of
      covariance (ANCOVA) was performed for the female patients. The sample size for
      males (n = 2) was too small for the latter analysis. RESULTS: Compared with
      normal subjects and their confidence intervals, subjects with Marfan's syndrome
      had an increased Ep and stiffness (beta) and decreased strain (fractional
      diameter change) in the infrarenal aorta. Furthermore, ANCOVA in the female
      patients showed increased beta (p < 0.01) and Ep (p < 0.01) and a decreased
      strain (p < 0.001). Aortic diameters, MAP, as well as the pulse pressure, were
      similar in the two groups. CONCLUSION: This investigation demonstrates
      alterations in the mechanical properties of the aorta in Marfan's syndrome in the
      form of increased stiffness of the aortic wall. This may be of importance in the
      pathogenesis of aortic dissection and rupture.

PMID- 7813728
TI  - Declining incidence of amputation for arterial disease in Scotland.
AB  - OBJECTIVES: To determine time trends and geographical variations in the incidence
      of major amputation for peripheral arterial disease and whether lower rates of
      amputation were related to higher rates of arterial reconstruction. DESIGN:
      Analysis of Scottish hospital discharge data. SETTING: Scotland 1981-1990.
      MATERIALS: Patients undergoing major amputation or arterial reconstruction for
      peripheral arterial disease. CHIEF OUTCOME MEASURES: Time trends in age-sex
      standardised rates of major amputation and arterial reconstruction, and
      correlation between the rates of these operations by health board. MAIN RESULTS:
      In Scotland, between 1981 and 1990, the incidence of major amputation fell by 22%
      (p < 0.001). Inconsistencies were observed within different age-sex groups. In
      the population under 65 years of age the incidence of amputation fell by 45% (p <
      0.001), whereas in those over 65 years the incidence increased by 54% (p <
      0.001). Amputation rates fell in men but a paradoxical increase was observed in
      women. Between 1981 and 1990, rates of arterial reconstruction doubled (p <
      0.001), with an increase in all age-sex groups. Rates of amputation and
      reconstruction varied between health boards of residence, with a positive
      correlation (r = 0.5) between rates of operations within health board. Therefore
      areas with higher reconstruction rates tended to have higher amputation rates.
      CONCLUSIONS: In Scotland, the incidence of amputation has fallen during a period
      when reconstruction rates have risen greatly. However inconsistencies in time
      trends by age-sex groups, and the lack of an inverse correlation by health board
      of residence, suggest that fewer amputations are unlikely to be due solely to an
      increase in reconstructive surgery.

PMID- 7813729
TI  - The fate of infrainguinal PTFE grafts and an analysis of factors affecting
      outcome.
AB  - Ninety-five infrainguinal polytetrafluoroethylene (PTFE) bypass grafts were
      performed in 90 patients. Indications for surgery were severe claudication in 23
      limbs (24%) and rest pain or tissue necrosis in 72 limbs (76%). Sixty-seven
      grafts (71%) were to the above knee popliteal artery and 28 (29%) to the
      infragenicular vessels. The primary, primary assisted and secondary graft
      patencies at 2 years in limbs with rest pain or tissue necrosis were 37, 42 and
      46% respectively with a limb salvage rate of 65%. A univariate analysis was
      performed to identify preoperative risk factors which affected graft patency.
      Smoking, an ankle systolic pressure of less than 50 mmHg, presentation with rest
      pain or tissue necrosis and single vessel run-off all had a significant adverse
      effect on graft patency. However, multivariate analysis revealed that smoking was
      the only significant adverse variable. These findings support the view that PTFE
      grafts for limb salvage are worthwhile even if the distal anastomosis is below
      the knee and run-off is via a single vessel provided that the patient stops
      smoking.

PMID- 7813730
TI  - An eight year experience of conservative management for aortic graft sepsis.
AB  - This paper describes the results of conservative management of 15 patients with
      aortic graft infection. The median time to presentation was 4 months. Six of
      eight grafts that were sent for culture grew organisms, of which the commonest
      were streptococci and coagulase negative staphylococci. Four patients did not
      receive intensive antibiotic treatment and all died of sepsis. Eleven patients
      received intensive intravenous and oral antibiotic therapy and appropriate
      surgical management; two of these died, one of a stroke and the other of an
      unknown cause. Two of the nine surviving patients had no surgery and the
      remainder had procedures to drain pus and unblock occluded grafts, including
      minimal graft excision in four patients, although two of these subsequently
      required total graft excision. The follow-up period for six of these nine
      patients is more than 4 years. For most patients with aortic graft infection
      aggressive antibiotic treatment supplemented by minimalist surgery is preferable
      to primary radical surgery.

PMID- 7813731
TI  - Complications following caval interruption.
AB  - Caval interruption is widely regarded as the treatment of choice for the
      prevention of recurrent pulmonary embolism (PE). The safety, ease of insertion
      and "convenience" of the devices are the main arguments for filter placement.
      Today many filters are placed for prophylactic reasons, sometimes without an
      established diagnosis of pulmonary embolism or underlying deep venous thrombosis.
      Early and late complications have been published but the rate is reported to be
      low, although only limited numbers of patients have been followed. In an 18-year
      period 11 patients with problems following caval interruption were treated, 10
      with acute complications, one with chronic caval occlusion. Six were treated
      conservatively, five underwent venous thrombectomy and a.v.-fistula. The device
      was removed in four. During the same period only three permanent filters were
      placed in our hospital (two with complications). Caval interruption is useful in
      selected high-risk patients and is the least invasive but not necessarily the
      best treatment. Provided stringent criteria are applied, the early and late
      complications can be accepted in order to prevent sudden death in patients with
      threatening massive PE. Extended or more liberal indications for caval
      interruption are neither necessary nor justified.

PMID- 7813732
TI  - Postoperative haemorrhage following aortic aneurysm repair.
AB  - Between 1988 and 1993, 17 (3%) out of a total 654 patients underwent reoperation
      for control of haemorrhage following repair of abdominal aortic aneurysm in a
      vascular surgery unit. The first operation was performed for rupture in 12 cases
      and electively in five. The incidence of reoperation for postoperative bleeding
      was 1.7% following elective operation and 3.3% following emergency operation.
      Case-controls, matched for sex and primary operation, were identified. The
      mortality rate in those requiring reoperation was 58% compared with 23% in the
      control group (p = 0.037). Seven patients suffered progressive deterioration and
      died in the early postoperative period. Of the remaining ten patients, four
      suffered unexpected serious complications; two a fatal cerebro-vascular accident
      (CVA), one a fatal myocardial infarction (MI) and the fourth a non-fatal CVA. The
      patients requiring reoperation had greater blood loss (p < 0.05), greater
      transfusion requirements and lower core temperatures (p < 0.05) at the end of
      their first operation than the control group. All except one of the patients who
      bled had evidence of coagulopathy and had lower platelet counts than the control
      group both before and after the first operation. At reoperation there were
      multiple minor bleeding points in 11 patients, no active bleeding points in two
      patients and a discrete bleeding point in four patients. In conclusion, re
      operation for control of postoperative haemorrhage is an uncommon complication
      which is strongly associated with coagulopathy, may predispose to "rebound"
      postoperative thrombotic episodes, and carries a poor prognosis.

PMID- 7813733
TI  - Transthoracic endoscopic sympathectomy for hyperhidrosis and Raynaud's
      phenomenon.
AB  - Over an 80 month period, 53 transthoracic endoscopic sympathectomies were
      performed in 34 patients. The indications for surgery were palmar hyperhidrosis
      in 20 procedures (38%), palmar and axillary hyperhidrosis in eight procedures
      (15%), Raynaud's phenomenon in 23 procedures (43%), and combined palmar
      hyperhidrosis and Raynaud's phenomenon in two procedures (4%). Follow-up data,
      obtained by a self-assessment postal questionnaire, was available for 47
      procedures in 30 patients (91%). Fourteen out of 15 procedures (93%) performed
      for palmar hyperhidrosis, all eight procedures (100%) for palmar and axillary
      hyperhidrosis and 14 out of 22 procedures (64%) performed for Raynaud's
      phenomenon produced an immediate improvement in symptoms. These improvements were
      sustained in 13 procedures (87%) performed for palmar hyperhidrosis, all
      procedures performed for palmar and axillary hyperhidrosis (100%) but only 10
      procedures (45%) performed for Raynaud's phenomenon at a median follow-up of 16,
      34 and 44.5 months respectively. There were no deaths nor postoperative Horner's
      syndrome in these patients. The only minor complications were two small
      pneumothoraces. Compensatory sweating was observed after 24 procedures (51%).
      These results confirm that transthoracic endoscopic sympathectomy is a simple,
      safe and effective procedure. In patients with hyperhidrosis, the results are
      excellent and prolonged; in patients with Raynaud's phenomenon, immediate
      improvement can be achieved but the symptoms may return with time.

PMID- 7813734
TI  - A surgical technique for post catheterisation femoral artery pseudoaneurysms.

PMID- 7813735
TI  - Spontaneous right haemothorax secondary to aortic rupture.

PMID- 7813736
TI  - Lower extremity acute ischaemia due to a metastatic breast fibrosarcoma embolism.

PMID- 7813737
TI  - Successful resection of two simultaneous aneurysms of the superior mesenteric and
      right renal artery.

PMID- 7813738
TI  - Post-traumatic intima dissection and thrombosis of the external iliac artery in
      sportsman.

PMID- 7813739
TI  - Failing aortic graft in adolescence--an effect of patient growth.

PMID- 7813740
TI  - [WHO epidemiologic studies in Hungary in 1985 and 1991].
AB  - In accordance with the Cooperative-Medium Term Program between Hungary and the
      WHO Regional Office for Europe, the basic oral health survey took place in 1985
      at 17 examination sites (8 urban and 9 rural areas). A total of 2684 persons in
      the groups 7 (894), 12 (893) and 35-44 (897) years of age were examined. At 12
      years of age, 92.5% of the children had dental caries with an average DMFT of
      5.00, of which 2.5 had untreated caries (DT), and 2.0 were filled (FT). At 35-44
      years of age the average DMFT per person was 15.8 of which 10.2 were missing. The
      number of extracted teeth in this age group must be characterized as very high,
      even though the percentage of edentulous persons was very low (0.3%). In this age
      group deep pockets (CPITN 4) were found in 8% of the persons. Due to the national
      oral health preventive program, which had been launched in 1986, at the second
      pathfinder survey (1991) we found favourable changes concerning the oral health
      condition. The geographical location of the examination sites was the same. A
      total of 2651 persons in the age groups 6 (898), 12 (898) and 35-44 (855) years
      were examined. Among 12 years old children the caries prevalence was 89.64%, the
      mean number of DMFT has decreased from 5.0 to 4.29, of which 2.03 had untreated
      caries (DT) and 1.93 were filled. Thus according to WHO criteria dental caries at
      12 years of age has become moderate in Hungary.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7813741
TI  - [Effect of various mouthwashes on wound healing after tooth extraction].
AB  - The results of the clinical tests involving 200 patients show that after
      extraction the use of Meridol, NaF and Chlorhexidine mouthrinses along with
      careful mouth hygiene helps healing to a great extent. The antiseptic affect of
      solutions in case of solutions of fluoride content are manifested in an
      antibacterial way, while solutions of chlorhexidine content act in an antiseptic
      way. Furthermore the solutions foster good oral hygiene and in this way lessen
      the number of complications. This is shown by the decreased frequency rate of
      gingivitis and also the opinions of the patients. Their reports confirm that
      there is less foetor ox ore, pain and functional insufficiency in mastication.
      Based on these facts we can state that any of the three mouthrinses considerably
      helps complication-free healing.

PMID- 7813742
TI  - Baroreceptor regulation of vasopressin and renin secretion: low-pressure versus
      high-pressure receptors.
AB  - The high-pressure or arterial baroreceptors and low-pressure or atrial receptors
      are believed to participate in the reflex control of arginine vasopressin (AVP)
      and renin secretion. The current concept of the control system is that at normal
      blood volume and pressure, afferent impulses from the receptors tonically inhibit
      central mechanisms controlling secretion of AVP and renin. Thus, a reduction in
      blood volume or pressure causes a decrease in receptor activity and a reflex
      increase in hormone secretion; conversely an increase in blood volume causes the
      opposite sequence of events. Furthermore, it is widely believed that cardiac
      atrial receptors are more important than arterial baroreceptors in the reflex
      control of AVP and renin secretion. Evidence presented in this review challenges
      the traditional view that cardiac receptors are importantly involved in the
      reflex control of AVP secretion. Recent evidence indicates that plasma AVP does
      not increase during progressive hypovolemia until volume loss causes a frank fall
      in arterial pressure. Furthermore, the evidence suggests that it is the sudden
      unloading of arterial baroreceptors that triggers the surge in AVP secretion and
      not signals from cardiac receptors. There is also very little evidence that
      increasing the load on cardiac receptors inhibits AVP secretion. In contrast,
      there is considerable evidence that renal sympathetic nerve activity, and hence
      reflex control of renin secretion, is tightly and inversely coupled to changes in
      blood volume. Furthermore, the evidence supports the concept that atrial
      receptors are the mediators of the fine reflex control of renin secretion in
      response to changes in blood volume.

PMID- 7813743
TI  - Anencephaly and other neural tube defects.

PMID- 7813744
TI  - Monoaminergic regulation of neuroendocrine function and its modification by
      cocaine.
AB  - Neuroendocrine pharmacology represents a potentially valuable approach to the
      assessment of alterations in neuronal function in the brain of human cocaine
      abusers. Neuroendocrine effects of the monoamine uptake inhibitor cocaine have
      predominantly been examined in laboratory animals. These preclinical studies may
      help to identify the optimal challenge tests to be performed in clinical studies.
      In laboratory animals, acute administration of cocaine activates the hypothalamic
      pituitary-adrenal axis, via actions on serotonergic and dopaminergic neurons in
      the brain. Cocaine also reduces prolactin secretion, probably by dopaminergic
      mechanisms, although the necessary studies to confirm this hypothesis have not
      been performed. Cocaine also reduces renin secretion, and increases vasopressin
      and luteinizing hormone secretion, by mechanisms which have not been clearly
      established. The adrenocorticotropin, corticosterone, prolactin, and renin
      responses to cocaine are generally unaltered by prior cocaine exposure,
      suggesting that tolerance or sensitization to the endocrine effects of cocaine
      does not occur. However, several studies have determined that prior cocaine
      exposure alters the serotonergic regulation of hormone secretion. Chronic cocaine
      exposure reduces some of the hormone responses to the serotonin (5-HT) releasers
      p-chloroamphetamine and d-fenfluramine, suggesting deficits in the functional
      status of serotonergic nerve terminals. Additionally, repeated cocaine exposure
      produces subsensitive 5-HT1A-mediated hormone responses, and supersensitive 5-HT2
      mediated responses. Alterations in dopaminergic- or noradrenergic-mediated
      hormone responses have not been examined in animals chronically exposed to
      cocaine. Endocrine studies in human cocaine abusers have largely examined basal
      hormone levels or the hormone responses to cocaine. Strong conclusions from these
      studies are limited because (1) many neuronal and nonneuronal systems regulate
      secretion of each hormone, so that alterations in basal hormone levels cannot be
      attributed to only one neurotransmitter; and (2) hormone responses to cocaine
      cannot be examined in cocaine-naive subjects due to ethical considerations,
      making it impossible to determine whether the response in cocaine abusers is
      abnormal. It may be more beneficial for studies in cocaine abusers to examine the
      hormone responses to drugs that specifically affect monoaminergic neurons and
      compare the data with cocaine-naive individuals.

PMID- 7813745
TI  - The outcome of pregnancy following untreated impaired glucose tolerance.
AB  - OBJECTIVE: To study the outcome of untreated impaired glucose tolerance (IGT)
      during pregnancy. METHODS: Two hundred twelve pregnant women with IGT and 212
      pregnant women with normal glucose tolerance. The main outcomes at delivery were
      mean gestation at delivery, incidence of preterm labor and induction of labor,
      modes of delivery, mean birthweight, mean Apgar score at 5 min, proportion of
      babies admitted to NICU, mean values of neonatal capillary blood glucose and
      hematocrit at 2 h of age. RESULTS: The mean age and parity of women with IGT
      during pregnancy were higher than those in control women. Their babies were
      heavier and had lower neonatal capillary blood glucose and higher hematocrit
      concentration than controls. However, the proportion of babies with birthweight >
      or = 2 S.D. above the mean, neonatal capillary blood glucose < 1.5 mmol/l (28
      mg/dl) or hematocrit > or = 65% were equal in both groups. CONCLUSION: IGT, as
      defined by the World Health Organization, did not result in any adverse outcomes.

PMID- 7813746
TI  - Cervical ripening in women with previous cesarean deliveries.
AB  - OBJECTIVE: To evaluate the safety and efficacy of preinduction cervical ripening
      in women with previous cesarean deliveries undergoing induction of labor.
      METHODS: Retrospective study of women with previous low transverse cesarean
      deliveries who underwent ripening of an unfavorable cervix prior to induction of
      labor (n = 89). Multiparas without previous cesarean deliveries undergoing
      ripening and induction of labor during the same time period were used for
      comparison (n = 61). Ripening was performed with prostaglandin E2 (PGE2) gel, or
      an osmotic dilator, or both. Induction of labor with oxytocin followed the
      American College of Obstetricians and Gynecologists' guidelines. Outcome data
      were analyzed using the unpaired Student's t-test or chi 2-test as appropriate.
      Significance was established at P < 0.05. RESULTS: The mean gestational age was
      39.6 +/- 2.6 and 38.2 +/- 2.9 weeks for the study and comparison groups,
      respectively. There were no differences between the groups in Bishop score,
      duration of the first stage of labor, maximum dose of oxytocin, indications for
      cesarean delivery, puerperal morbidity, birthweight, Apgar scores or NICU
      admissions. Sixty-four percent (57 of 89) of study women delivered vaginally
      compared with 82% (50 of 61) of women in the comparison group (P < 0.03). The
      data were analyzed separately for those women undergoing cervical ripening with
      PGE2 gel only. No differences were observed between the groups in any of the
      categories mentioned above. CONCLUSION: Cervical ripening appears to be safe and
      effective in women with previous low transverse cesarean deliveries undergoing
      induction of labor with an unfavorable cervix.

PMID- 7813747
TI  - Quantification of immunoglobulin A in chorioamniotic membrane of patients with
      premature rupture of membranes.
AB  - OBJECTIVE: The proposal was to study the presence of immunoglobulin A (IgA) in
      the chorioamniotic membrane of healthy postpartum women with premature rupture of
      the chorioamniotic membrane (PROM). METHOD: A single radial immunodiffusion
      technique was used to quantify the IgA in the chorioamniotic membrane tissues.
      RESULTS: The level of IgA was approximately 10 times higher in patients whose
      membranes had been ruptured for > 10 h (24.58 mg/dl). These results were compared
      with those of a previously published study where the mean of amount of IgA was
      2.52 mg/dl in membranes of patients with rupture < 10 h. Our results show that
      IgA began to rise after 10-15 h following rupture. CONCLUSION: Although more
      studies need to be performed our data indicate that the increasing IgA in our
      patients after 10 h of latency probably represents the beginning of an ascending
      colonization of bacteria which could be the source of future infection.

PMID- 7813748
TI  - Umbilical cord venous progesterone at term delivery in relation to mode of
      delivery.
AB  - OBJECTIVE: To determine whether the umbilical cord venous progesterone at term
      delivery is related to the mode of delivery. METHODS: Thirty-nine pregnant
      patients at term were divided into three groups: elective cesarean section
      (control), spontaneous vaginal delivery, and emergency cesarean section.
      Umbilical cord venous and maternal serum progesterone were measured by
      radioimmunoassay. Statistical analysis was carried out using Student's t-test,
      with the level of significance set at P < 0.05. RESULTS: Umbilical cord venous
      progesterone was significantly higher in babies delivered by emergency cesarean
      section (P < 0.001) and in those who had spontaneous vaginal delivery (P < 0.02),
      compared with the control group. Maternal serum progesterone concentrations
      showed no significant differences between the three groups. The Apgar scores of
      the stressed group of babies were significantly lower (P < 0.001). CONCLUSION:
      The findings demonstrate that the fetuses exposed to stress during labor produce
      higher progesterone secretion. This could be one possible way the fetus protects
      itself against the sequelae of hypoxia.

PMID- 7813749
TI  - Malignant mixed Mullerian tumors of the uterus.
AB  - OBJECTIVE: To review the prognostic factors of Chinese women with mixed Mullerian
      tumors of the uterus. METHOD: A retrospective review of 21 cases of malignant
      mixed Mullerian tumors of the uterus treated during the 10-year period from 1980
      to 1990. RESULTS: All patients except one were postmenopausal. The incidence of
      previous pelvic irradiation was 9.5%. The most common presenting symptom was
      abnormal vaginal bleeding. One-third of patients yielded an abnormal cervical
      smear. Treatment included surgery, chemotherapy and radiotherapy in the majority
      of patients. Prognosis was poor with only three long-term survivors, all with
      stage-I homologous tumors with superficial myometrial invasion. The survival rate
      for stage-I and -II disease at 2 years was 50% and for more advanced disease
      extending beyond the uterus was 0%. The survival rate for all stages at 5 years
      was 14.3%, and the cumulative probability of survival at 5 years was 0.165.
      CONCLUSION: The most important prognostic factors appear to be the extent of
      tumor involvement at the time of diagnosis and the depth of myometrial invasion.

PMID- 7813750
TI  - Neonatal survival after preterm premature rupture of membranes secondary to first
      trimester chorionic villus sampling.
AB  - A case of preterm premature rupture of membranes (PROM) secondary to first
      trimester chorial biopsy is described. The newborn survived and physical and
      psychological development was normal at 1 year of age. On review of the
      literature, different attitudes may be found with regard to the treatment of
      PROM: some authors prefer expectant management while others defend extraction of
      the fetus when reasonable maturity is reached. In both cases the outcome is
      usually poor for the fetus.

PMID- 7813751
TI  - Two patients with postpartum HELLP syndrome after a normotensive twin pregnancy.
AB  - Two patients with postpartum HELLP syndrome after a normotensive twin pregnancy
      are presented. As seen in one of the patients, morbidity can be significant.
      These cases illustrate that even after uneventful pregnancies one should be on
      the alert for symptoms of HELLP syndrome. If symptoms exist laboratory
      investigations should be carried out.

PMID- 7813752
TI  - Fetal gender effect on preterm and term preeclamptic pregnancies.

PMID- 7813753
TI  - Candidal cystitis in pregnancy treated with amphotericin B.

PMID- 7813754
TI  - Estrogen receptors in a urethral leiomyoma presenting in pregnancy.

PMID- 7813755
TI  - A unique case of Meigs' syndrome.

PMID- 7813756
TI  - Extra marker chromosome, dic(22)(q11), associated with gonadal dysgenesis and
      multiple malformations.

PMID- 7813757
TI  - Substance abuse. ACOG Technical Bulletin Number 194--July 1994.
AB  - Obstetrician-gynecologists have a clear role in substance abuse prevention and
      treatment. Knowledge of key risk factors, familiarity with substance abuse
      screening techniques, and identification of the symptoms and signs of abuse are
      all components in this process.

PMID- 7813758
TI  - Epidemiological correlates of preterm premature rupture of membranes.
AB  - OBJECTIVE: To study the clinical risk factors for preterm premature rupture of
      membranes (PROM). METHOD: We conducted a case-control study of 138 patients with
      PROM between 24 and 35 weeks' gestation and 267 control subjects. RESULTS: In
      stepwise multiple logistic regression models, the population of cases was more
      likely to be of low social class. Other risk factors for PROM were smoking in
      pregnancy, 1st or 2nd-3rd trimester hemorrhages, cervical incompetence and a
      documented cervico-vaginal infection during index pregnancy. First trimester
      hemorrhage and a documented cervico-vaginal infection during index pregnancy were
      associated with preterm PROM both in nulliparous and in multiparous women.
      CONCLUSION: Few potentially remediable risk factors are associated with the
      occurrence of preterm PROM.

PMID- 7813759
TI  - Substance abuse in pregnancy. ACOG Technical Bulletin Number 195--July 1994
      (replaces No. 96, September 1986).
AB  - Substance abuse by pregnant women continues to be one of the leading problems in
      modern obstetrics. The frequency of abuse of more than one substance, especially
      with alcohol and tobacco, makes interpretation of the literature difficult;
      however, there is little doubt that substance abuse is associated with poor
      pregnancy outcome. Furthermore, abstinence and prenatal care are associated with
      improved perinatal outcomes. Despite the positive impact of perinatal care,
      however, continued abuse of substances during pregnancy can result in infant
      impairment. Clinicians who provide care to pregnant women should be alert to the
      possibility of substance abuse in all women so that treatment can be offered and
      complications can be anticipated, or better, avoided. At the time of the first
      prenatal visit, all pregnant women should be questioned thoroughly about past and
      present drug use. While toxicology screening may be helpful in some
      circumstances, universal screening is not recommended. Practitioners should be
      familiar with testing and reporting requirements in their state. Substance
      abusers should be counseled about the risks posed by continued substance use. At
      each prenatal and postpartum visit, substance abuse treatment should be offered
      to those who have not quit. When possible, it is helpful to work with a
      multidisciplinary team to address the various problems associated with substance
      abuse.

PMID- 7813760
TI  - Ethical framework for gynecologic and obstetric care.

PMID- 7813761
TI  - Ethical considerations concerning the use of anti-progestins.

PMID- 7813762
TI  - In memoriam Sir Vincent Brian Wigglesworth (1899-1994).

PMID- 7813763
TI  - Signal propagation and regulation in the mating pheromone response pathway of the
      yeast Saccharomyces cerevisiae.
AB  - Extracellular signals can affect the rate of proliferation and the state of
      differentiation of eukaryotic cells. Signal transduction pathways have evolved to
      detect these signals at the plasma membrane, transmit them through the cytoplasm
      and into the nucleus, and thereby generate the appropriate changes in metabolism
      and transcription. Much attention has been focused recently on regulatory
      pathways of this sort that lead to activation of a family of protein kinases
      known as the mitogen- or messenger-activated, or extracellular signal-regulated
      protein kinases (MAPKs or ERKs) because this particular class of enzyme is highly
      conserved among eukaryotes, as is documented here and in the accompanying reviews
      in this issue. The mating pheromone response pathway in a unicellular microbe,
      the budding yeast Saccharomyces cerevisiae, is perhaps the best understood
      multicomponent signaling pathway known in any eukaryotic organism, especially at
      the genetic level. Furthermore, structural homologs and functional analogs of the
      components of the yeast pheromone response pathway are recapitulated in the
      signaling systems present in multicellular eukaryotes. This article emphasizes
      recent findings and common molecular themes for understanding the organization
      and regulation of MAPK-dependent signaling cascades that have emerged from
      biochemical and genetic analysis of the mating pheromone response pathway in
      yeast.

PMID- 7813764
TI  - The torso pathway in Drosophila: lessons on receptor tyrosine kinase signaling
      and pattern formation.
AB  - Pattern formation at the anterior and posterior termini of the Drosophila embryo
      involves intercellular communication via the Torso receptor tyrosine kinase
      (RTK). Recent advances in the understanding of Torso signaling has provided
      further support for the conservation of a signal transduction cassette downstream
      of RTKs. In addition, the analysis of the Torso pathway has begun to reveal
      general molecular mechanisms by which cells may impart patterning information to
      their neighbors through the use of RTKs.

PMID- 7813765
TI  - Signaling by wingless in Drosophila.
AB  - Wingless, a member of the Wnt gene family, is an essential gene for segmentation
      in Drosophila, and is also involved in many other patterning events. The gene
      encodes a secreted protein that can regulate gene expression in adjacent cells.
      Recently, significant progress has been made in elucidating the signal
      transduction pathway of wingless, mainly by genetic experiments but increasingly
      also at the biochemical level. While many components of wingless signaling, in
      particular a receptor, remain to be identified, our current understanding of
      wingless pathway is more advanced than that of other Wnt genes. We will give an
      overview of the various roles of wingless in development, and we will then
      summarize the wingless signaling pathway as it has emerged from genetic and
      biochemical studies. Where appropriate, wingless signaling will be compared to
      the activity of vertebrate Wnt proteins.

PMID- 7813766
TI  - Delta-notch signaling and Drosophila cell fate choice.
AB  - Delta and Notch encode cell surface proteins that function in a wide variety of
      cell fate specification events during oogenesis, embryogenesis, and metamorphosis
      in Drosophila melanogaster. Various lines of evidence imply that Delta and Notch
      proteins function as signal and receptor in cellular interactions required for
      the partitioning of fates among cells within equivalence groups in many
      developmental contexts. Molecular and genetic observations provide a framework
      for the formulation of hypotheses concerning the mechanisms by which the Delta
      ligand and Notch receptor interact and the Delta-Notch signal is transduced in a
      manner that can affect the adoption of distinct fates by different cells. In
      particular, emerging evidence regarding the expression and function of Delta and
      Notch during development also raise possible alternatives to the currently
      favored hypothesis that Delta-Notch interactions generate instructive signals
      that mediate a process termed lateral inhibition.

PMID- 7813767
TI  - Signal transduction during the development of the Drosophila R7 photoreceptor.

PMID- 7813768
TI  - Extending and connecting signaling pathways in C. elegans.
AB  - The development of the nematode Caenorhabditis elegans is known to depend
      extensively on reproducible cell-cell interactions. The analysis of many of these
      signaling events has revealed that, in most cases, the mechanisms that mediate
      them have been conserved throughout metazoan evolution. Thus, the analysis of
      signaling pathways in C. elegans can aid in the understanding of signal
      transduction mechanisms in general. In this review we focus on signaling events
      that occur during the development of the hermaphrodite egg-laying system. Many of
      these signaling events occur at approximately the same time and in very close
      proximity to one another. Following a brief review of the individual signaling
      systems employed, we analyze the data that have started to address how the
      specificity among these pathways is maintained and how multiple pathways that
      affect individual developmental decisions are integrated. These issues are common
      to all signaling systems and should be instructive in presenting the complexities
      that are involved in obtaining a global understanding of development.

PMID- 7813769
TI  - Correction of abnormal retinal pathways found with albinism by introduction of a
      functional tyrosinase gene in transgenic mice.
AB  - In albino mammals the pattern of connections between the eye and the brain is
      systematically disrupted at the optic chiasm, with a proportion of axons that
      should project ipsilaterally being rerouted to the contralateral hemisphere of
      the brain. Albino mice carry a mutation at the c-locus, which encodes the
      tyrosinase gene. Tyrosinase is the key enzyme in melanin synthesis. In this study
      we have used transgenic mice generated from an albino strain in which a
      functional tyrosinase transgene within a yeast artificial chromosome has been
      inserted. We have examined the chiasmatic pathways in these and control animals
      and have demonstrated that the abnormality is corrected in the tyrosinase
      transgenic mice. The results of this study identify the key element in this
      abnormality. The establishment of the transgenic model provides a unique tool
      with which to investigate the way in which melanin shapes this region of the
      developing mammalian visual system.

PMID- 7813770
TI  - Expression patterns of Hoxb genes in the Xenopus embryo suggest roles in
      anteroposterior specification of the hindbrain and in dorsoventral patterning of
      the mesoderm.
AB  - Hox genes are thought to participate in patterning the anteroposterior (a-p) axis
      during vertebrate embryogenesis. In this investigation, the spatial expression of
      six Hoxb genes was analyzed in early embryos of Xenopus laevis by in situ
      hybridization. Hoxb gene expression was first detected in late gastrulae/early
      neurulae, by which stage, the characteristic spatially colinear Hoxb gene
      expression sequence was already apparent. Dissection experiments indicated that
      the establishment of these localized expression patterns coincides with the
      acquisition of anteroposterior positional information along the main body axis.
      The Hoxb genes continued to be expressed in similar domains along the
      anteroposterior axis at all developmental stages examined, although there were
      some changes in expression at the cellular level. Interestingly, the 3' genes,
      Hoxb-1, Hoxb-3, and Hoxb-4 were expressed in very restricted domains in the
      future hindbrain, while Hoxb-5, Hoxb-7, and Hoxb-9 transcripts were present along
      the entire presumptive spinal cord. It was thus notable that the 5' Hoxb genes
      exhibited different types of expression domain than the 3' Hoxb genes. These
      observations suggest that there may be different mechanisms regulating the
      expression of the 3' and 5' Hoxb genes. Expression of all of the Hoxb genes
      analyzed, except Hoxb-4, was predominantly detectable in the central nervous
      system or in neural crest-derived structures. Hoxb-4 mRNA was detected in the
      central nervous system, but interestingly, the major expression site for this
      gene was the somites. The other Hoxb genes tested failed to show significant
      expression in the somitic mesoderm, although transcripts from genes 5' from Hoxb
      4 were detected in other mesodermal tissues. In the vertebrate trunk,
      anteroposterior patterning of the CNS is thought to be regulated by the somites.
      The results obtained here for Xenopus embryos did not explicitly support the idea
      of a Hoxb code for the somites, although we cannot rule this out. Instead,
      interestingly, the data were consistent with a role for Hoxb genes in
      dorsoventral patterning of the mesoderm.

PMID- 7813771
TI  - A three-step mechanism of action of thyroid hormone and mesenchyme in metamorphic
      changes in anuran larval skin.
AB  - The mesenchyme of the anuran tadpole has been known to induce the regional
      specificity of epidermis which is expressed during metamorphosis as a body (head
      and trunk)-or a tail-specific change: the former epidermis transforms into the
      adult-type, while the latter commits programmed cell death. The inductive
      activity of the mesenchyme was characterized in relation to both its
      premetamorphic structural change and the action of thyroid hormone (TH). The
      epidermis and the mesenchyme were obtained from the body and the tail of tadpoles
      of the bullfrog Rana catesbeiana at stages IV or X defined by Taylor and Kollros
      (1946), recombined heterotypically, and were autografted to see the mesenchymal
      effect on the characteristics of the epidermis. The mesenchyme at stage IV showed
      inductive activity toward the epidermis and changed its inherent characteristics,
      while the mesencheme at stage X lost it. The skin at stage IV showed uniformity
      in its structure over the entire surface of the animal. The histology of stage X
      skin was region-dependent. The connective tissue was newly developed between the
      skin basement membrane and thick collagen lamella in the body but not in the
      tail. A trace of TH was suggested to be involved in inducing these mesenchymal
      changes, because the treatment of tadpoles at stage IV with thiourea inhibited
      the appearance of new connective tissue. A three-step mechanism in the
      metamorphic changes of the tadpole skin is proposed: (1) TH-independent early
      premetamorphic induction; (2) premetamorphic remodeling induced by a trace of TH;
      and (3) metamorphic remodeling triggered by a high dose of TH.

PMID- 7813772
TI  - Evidence by a voltage clamp study of an electrically mediated block to polyspermy
      in the egg of the ascidian Phallusia mammillata.
AB  - Eggs of the ascidian Phallusia mammillata were voltage clamped (from -100 to +60
      mV) and inseminated with a low or heavy sperm concentration. From inseminations
      with low sperm concentration (1 x 10(6) sp/ml), we found that fertilization
      currents occurred between -100 and +40 mV: they were always inward and displayed
      an analogous pattern whatever the clamped voltage. We established that the
      percentages of inseminated eggs that produced a fertilization current varied as a
      function of the clamped voltage. These percentages were not statistically
      different from 100% at clamped voltages between -100 and -30 mV, they decreased
      to 68 and 56% at clamped Vm of -10 and 0 mV, respectively, but were not
      statistically different from 0% at clamped Vm between +10 and +40 mV. We never
      obtained any egg electrical response at a clamped voltage of +50 mV. Almost all
      eggs (96%) which responded electrically were penetrated by one or several
      spermatozoa. These eggs were resuming meiosis (81 to 50%) at values of clamped Vm
      between -100 and 0 mV, respectively. At clamped Vm between +10 and +50 mV, the
      percentages of eggs resuming meiosis were not statistically different from 0.
      These results indicate that in P. mammillata eggs, the occurrence of an
      electrical response is voltage dependent and consequently that the initial
      depolarizing shift of the fertilization potential constitutes a fast block to
      polyspermy. However, in this species, the sperm penetration is not voltage
      dependent, since it occurred at clamped Vm from -100 to +40 mV. On the other
      hand, when eggs were clamped from -100 to +60 mV and inseminated with a heavy
      sperm concentration (2 x 10(7) sp/ml), the curves expressing, respectively, the
      percentages of eggs which responded electrically, the percentages of eggs which
      were penetrated by one or several spermatozoa, and the percentages of eggs
      resuming meiosis, as functions of the clamped Vm, were shifted by approximately
      35 mV toward more positive voltages, compared to the corresponding curves
      obtained from eggs inseminated with a low sperm concentration. This last result
      means that the critical value of the membrane potential which characterizes the
      electrical block to polyspermy is dependent on the sperm concentrations used for
      inseminations.

PMID- 7813773
TI  - Embryonic expression of motoneuron topography in the rat diaphragm muscle.
AB  - The phrenic motoneuron pool of the rat projects onto the diaphragm muscle with a
      distinct rostrocaudal bias. This bias is detectable at birth and is reestablished
      following denervation. In an effort to define the mechanisms underlying this
      topographic bias, we asked whether growing phrenic motoneurons select their
      muscle contacts initially upon first contact or whether the initial neuromuscular
      distribution is random, to be specified later through synaptic rearrangement. The
      onset of neurotransmission in embryonic diaphragm muscles aged E-14 to E-18 was
      studied using focal extracellular microelectrodes. Two important phenomena were
      observed. First, motoneurons from all three cervical ventral roots (C4, C5, and
      C6) establish functional innervation at the same time. Second, already at E-15,
      when the earliest synaptic potentials could be recorded, a distinct rostrocaudal
      bias was detected. This bias was amplified as innervation progressed to rostral
      and caudal sectors during E-16 to E-18. These results suggest that growing
      phrenic motoneurons make topographic choices as they navigate toward their muscle
      targets. Moreover, the results indicate that further research into the mechanisms
      for topographic selectivity should focus on initial nerve-muscle contacts in the
      embryo, rather than secondary processes of error correction.

PMID- 7813774
TI  - The expression pattern of two zebrafish achaete-scute homolog (ash) genes is
      altered in the embryonic brain of the cyclops mutant.
AB  - Two achaete-scute homolog sequences, Zash-1a and Zash-1b, were isolated from a
      zebrafish embryonic cDNA library. The Zash-1a cDNA encodes a protein very similar
      to rat Mash-1 and Xenopus Xash-1, with over 94% identity in the C-terminal three
      fourths of all three polypeptides. The Zash-1b cDNA encodes a more distantly
      related protein, with 80% identity of amino acids to Mash-1 in this part of the
      sequence. At 24 hr, the Zash-1a transcripts are found in the hindbrain in two
      bilaterally symmetrical lines of cells which mark the boundary between the alar
      and basal plates and in rhombomere 1 in ventral cells near the floorplate. The
      gene is also expressed in particular regions of the telencephalon and
      diencephalon, in the epiphysis, the ventral tegmentum, the neural retina, and in
      specific cells in the spinal cord. Zash-1b transcripts are found in the hindbrain
      in segmentally arranged fan-like groups of cells which are located close to the
      anterior and posterior boundaries of each of rhombomeres 2-6 and in ventral cells
      close to the floor plate of most rhombomeres. The gene is also expressed at sites
      distinct from cells expressing Zash-1a in the tegmentum, diencephalon,
      telencephalon, and spinal cord. In the mutant cyclops, Zash-1a transcripts are
      absent from the ventral region of the tegmentum and in the ventral cells of
      rhombomere 1, while more dorsal expression regions are unaffected. The effects of
      the mutation on Zash-1b expression, however, are more complex. In the hindbrain,
      the ventral expression zone of this gene is absent, the more dorsal segmented
      expression is disorganized, and ectopic expression in the alar plate is observed.
      A dramatic ectopic expression is also observed in the anterior tegmentum. The
      cyclops gene, therefore, has both positive and negative effects on the CNS of the
      wild-type embryo: it is required for activation of both Zash-1a and -1b in
      particular ventral cells, but it also restricts the expression of Zash-1b in
      other ventral cells and in some dorsal regions. Zash-1a and -1b gene probes will
      be extremely useful in the analysis of additional mutations affecting development
      of the central nervous system in zebrafish embryos.

PMID- 7813775
TI  - Etl2, a novel putative type-I cytokine receptor expressed during mouse
      embryogenesis at high levels in skin and cells with skeletogenic potential.
AB  - The regulatory effects of signaling proteins like hormones, growth factors, and
      cytokines are mediated by specific cell surface receptors which are grouped into
      distinct families on the basis of structural criteria. Here we report on the
      isolation and embryonic expression of a novel mouse gene, Etl2 (enhancer trap
      locus 2) which, based on its deduced amino acid sequence, constitutes a new
      member of the cytokine type-I receptor family. Among type-I receptors Etl2 is
      most similar to the alpha subunits of the human ciliary neurotrophic factor
      (CNTF) receptor and the mouse interleukin-6 (IL6) receptor with 32 and 30%
      identical amino acids, respectively. From Day 9 p.c. (postcoitum) onward low
      levels of Etl2 mRNA were detected in mesenchymal cells throughout the embryo and
      in parts of the nervous system, in particular in the ependymal linings of the
      spinal cord and the developing brain vesicles and in the neuronal layer of the
      retina. Highest levels of Etl2 expression were found on Day 12.5 p.c. in the
      craniofacial mesenchyme and during subsequent development in mesenchymal cells
      around all developing cartilages. At later stages, Etl2 transcripts were abundant
      in the dental papilla, the dermis, and hair follicles, as well as in the
      perichondrium and periost, i.e., in regions containing chondro and osteo
      progenitor cells. Etl2 mRNA was not detected, however, in mature odontoblasts,
      chondroblasts, osteoblasts, chondrocytes, and osteocytes. Our results suggest
      that Etl2 is a new orphan receptor belonging to the type-I cytokine receptor
      family and that Etl2 might have regulatory functions, particularly in the control
      of proliferation and/or differentiation of skeletogenic progenitor and other
      mesenchymal cells.

PMID- 7813776
TI  - gamma Interferon expression disrupts lens and retinal differentiation in
      transgenic mice.
AB  - We previously generated an animal model for the study of autoimmune diseases of
      the eye by targeting gamma interferon (gamma IFN) expression to the lens of
      transgenic mice. Here, we have studied the effect of constitutive lens expression
      of gamma IFN on eye development of these transgenic mice. By Day 18 of embryonic
      development, lens and retinal differentiation programs are completely disrupted;
      normal lens epithelia and fibers are replaced by balloon-like cells and retinal
      differentiation into inner and outer neuroblastic layers is already affected. The
      mRNA levels of gamma E- and/or gamma F-crystallin and MIP, markers of lens cell
      differentiation, are drastically reduced, while expression of ICSBP, a gamma IFN
      inducible transcriptional factor, is induced in the alpha ACry-gamma IFN
      transgenic mouse eyes. Taken together, our results suggest that constitutive
      expression of gamma IFN and its induction and activation of gamma IFN-inducible
      transcriptional factors in the eye altered the developmental fate of cells
      destined to become lens fiber cells by altering the pattern of lens gene
      expression.

PMID- 7813778
TI  - Meiosis reinitiation from the first prophase is dependent on the levels of
      intracellular Ca2+ and pH in oocytes of the bivalves Mactra chinensis and Limaria
      hakodatensis.
AB  - Naturally spawned oocytes of the marine bivalves Mactra chinensis and Limaria
      hakodatensis are arrested at the first prophase (prophase-I) and the first
      metaphase, respectively, until fertilization. Using the Ca2+ indicator fura-2 and
      the pH indicator 1-hydroxypyrene-3,6,8-trisulfonic acid, we have examined the
      respective effects of intracellular Ca2+ ([Ca2+]i) and pH (pHi) on meiosis
      reinitiation from prophase-I in oocytes of the two species. Shortly after
      insemination, Mactra oocytes displayed a transient [Ca2+]i increase followed by a
      period of sustained [Ca2+]i elevation. Removal of external Ca2+ shortly after
      fertilization immediately decreased the elevated [Ca2+]i to the resting level and
      inhibited germinal vesicle breakdown (GVBD); 100% GVBD was obtained when elevated
      [Ca2+]i above the threshold level (F340/F380: approximately 0.55) was kept for at
      least 5 min. Fertilized Mactra oocytes also showed a gradual pHi rise; sperm
      induced GVBD was blocked when pHi was maintained below the threshold level
      (F450/F380: approximately 0.95) by adding ammonia and acetate to the bath after
      insemination. In contrast, 2 mM ammonia caused a pHi rise and GVBD in Limaria
      oocytes without much affecting the [Ca2+]i level. For obtaining 100% GVBD, pHi
      had to be maintained for at least 5 min above the threshold level (F450/F380:
      approximately 0.9), which is similar to that in Mactra. Resting [Ca2+]i levels
      (F340/F380: approximately 0.65) in Limaria prophase-I oocytes were higher than
      the threshold level for GVBD in fertilized Mactra oocytes. It is possible that
      maintenance of both [Ca2+]i and pHi above threshold levels are required for GVBD
      and the levels are about the same in Mactra and Limaria, assuming that spectral
      characteristics of the indicators are the same in oocytes of the two species.

PMID- 7813777
TI  - Characterization of tolloid-related-1: a BMP-1-like product that is required
      during larval and pupal stages of Drosophila development.
AB  - The Drosophila tolloid (tld) gene product belongs to a family of developmentally
      important proteins that includes bone morphogenetic protein-1 (BMP-1). In
      Drosophila, tld is required at the blastoderm stage to establish pattern within
      the dorsal half of the embryo. Genetic analysis suggests that the major function
      of tld is to augment the activity of the decapentaplegic gene product, a close
      relative of the TGF-beta superfamily members, BMP-2 and BMP-4. In this report, we
      describe a new gene called tolloid-related-1 (tlr-1) that maps immediately
      proximal to tld. Sequence analysis indicates that tlr-1 has a large N-terminal
      extension relative to tld, but otherwise shows the same general organization of
      sequence motifs found in tld and other BMP-1 family members. These include a
      region of similarity to astacin, a crayfish metalloprotease, five copies of a
      repeat first found in complement proteins C1r and C1s, and two copies of an
      epidermal growth factor-like sequence. In situ hybridization experiments show
      that tlr-1 expression partially overlaps tld expression in early embryos, but
      shows unique transcriptional patterns in late stage embryos that are not seen
      with tld. In larval stages, both genes are expressed in identical patterns in
      imaginal discs and in the optic lobes of the brain, but tlr-1 is more abundant
      than tld. Deletions that eliminate tlr-1 expression cause lethality during larval
      and pupal stages of development. A small proportion of homozygous mutant flies
      eclose and show wing veination defects. Transgenic animals in which a tlr-1 cDNA
      is driven by the tld promoter fail to rescue tld mutations, and extra copies of
      tld fail to rescue tlr-1 mutations, implying that these genes have evolved
      functionally distinct features. We propose that tld and tlr-1 arose by gene
      duplication and that each has evolved independently to acquire distinct tissue
      specific roles in Drosophila development.

PMID- 7813779
TI  - Induction of alveolar type II cell differentiation in fetal tracheal epithelium
      by grafted distal lung mesenchyme.
AB  - Normal branching morphogenesis and cytodifferention of the lung require a
      specific interaction between the epithelial rudiment and pulmonary mesenchyme.
      Previous studies in the mouse have shown glandular stage pulmonary mesenchyme can
      elicit a lung-like pattern of branching morphogenesis when grafted onto tracheal
      epithelium of the same age that has been denuded of its own mesenchyme. We have
      examined whether are not this pattern of branching is accompanied by changes in
      epithelial cytodifferentiation. Purified pulmonary mesenchyme was isolated from
      the distal tips of day 13-14 fetal rat lungs and grafted onto a stretch of
      tracheal epithelium from which the mesenchyme had been removed. The grafts were
      cultured on semisolid 0.5% agarose in Waymouth's medium containing 10% serum for
      5 days and then for an additional 2 days in the same medium containing 10(-6) M
      cortisol. Unoperated or operated-ungrafted tracheae and intact lung explants
      served as controls. Grafting distal tip pulmonary mesenchyme onto the tracheal
      epithelium induced a pattern of branching identical to that seen in control lung
      explant cultures, while ungrafted control tracheal cultures formed cystic
      structures. Light microscopy of the induced tracheal epithelium showed that the
      constituent cells exhibited a morphology virtually identical to cells in control
      lung explants. Ultrastructural analysis demonstrated that the induced tracheal
      epithelial cells contained lamellar inclusion bodies, and the lumina of the
      induced acinar structures contained tubular myelin figures. Reverse transcription
      polymerase chain reaction analysis of the induced tracheae revealed the presence
      of mRNAs for surfactant protein A (SP-A) and SP-B, as well as SP-C, which is a
      specific marker for type II cell differentiation in the adult rat. Control
      tracheal cultures contained mRNAs only for SP-A and SP-B. Immunocytochemistry
      demonstrated that many cells within the induced tracheal epithelium were positive
      for SP-A and SP-C proteins. Further studies demonstrated that the ability of
      mesenchyme to induce tracheal epithelium varied within the pulmonary tree, and
      that the competence of the tracheal epithelium to respond to the influence of
      distal tip mesenchyme was temporally restricted. Our results demonstrate that
      pulmonary mesenchyme can act instructively on the tracheal epithelium to induce a
      program of type II cell differentiation.

PMID- 7813780
TI  - Involvement of an inhibitory G-protein in the signal transduction pathway of
      maturation-inducing hormone (17 alpha,20 beta-dihydroxy-4-pregnen-3-one) action
      in rainbow trout (Oncorhynchus mykiss) oocytes.
AB  - To investigate the mechanism by which the hormone 17 alpha,20 beta-dihydroxy-4
      pregnen-3-one(17 alpha,20 beta-DP) acts on a receptor on the external surface of
      rainbow trout oocytes to induce maturation, the interaction between 17 alpha,20
      beta-DP receptors and G-proteins was examined. Pertussis toxin (PT) catalyzed the
      ADP ribosylation of a 40-kDa protein in crude membranes from rainbow trout
      postvitellogenic oocytes, and cholera toxin (CT) labeled several proteins,
      including a major protein with an apparent molecular weight of 43 kDa. The 40-kDa
      protein was recognized by an antibody against the alpha subunit of inhibitory G
      proteins (Gi), whereas the 43-kDa protein was recognized by an antibody against
      the alpha subunit of stimulatory G-proteins (Gs). Treating the membrane fraction
      with 17 alpha,20 beta-DP decreased the PT-catalyzed ADP ribosylation of the 40
      kDa protein. In contrast, there was no significant change in the CT-catalyzed
      ribosylation of the 43-kDa protein after exposure to 17 alpha,20 beta-DP. The
      specific binding of 17 alpha,20 beta-DP to membrane fractions was decreased by
      PT. 17 alpha,20 beta-DP binding was also inhibited by nonhydrolyzable GTP analogs
      such as guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) and
      guanylylimidodiphosphate (GppNHp), but not by either ATP or guanosine 5'-O-(2
      thiodiphosphate) (GDP beta S). Scatchard analysis revealed that GppNHp induced a
      3.8-fold increase in the dissociation constant without a significant change in
      the number of binding sites, suggesting that the GppNHp-induced decrease in 17
      alpha,20 beta-DP binding is due to the decrease in binding affinity between 17
      alpha,20 beta-DP and its receptors. We conclude that the PT-sensitive Gi is
      involved in the signal transduction pathway of 17 alpha,20 beta-DP in rainbow
      trout oocytes.

PMID- 7813781
TI  - Intracellular calcium mobilization regulates the activity of 26 S proteasome
      during the metaphase-anaphase transition in the ascidian meiotic cell cycle.
AB  - Intracellular proteins ligated to ubiquitin are degraded by the 26 S proteasome
      which is composed of the 20 S proteasome and a regulatory subunit complex. We
      have reported that ATP-dependent activity of the proteasome is activated
      periodically during the ascidian mitotic division cycle. In the present study, we
      examined changes in the activities and in the amounts of proteasomes during
      progression of the ascidian meiotic division cycle. During the metaphase-anaphase
      transition triggered by treatment with calcium ionophore, the activity of 26 S
      proteasome was found to be enhanced transiently and then decreased. The change in
      proteasome activity was completely abolished by pretreatment with a cell
      permeable calcium chelating agent, BAPTA-AM, which indicates that proteasome
      activity is regulated by intracellular calcium mobilization. By immunoblot
      analyses, it was demonstrated that the 26 S proteasome underwent a change in
      amount in a manner similar to the change in its activities. The immunoblot
      analyses also indicated an inverse relation between the level of the 26 S
      proteasome and that of the 20 S proteasome throughout the cycle. These results,
      together with the fact that total amounts of the 26 S and 20 S proteasomes remain
      constant throughout the cycle, suggest that 26 S proteasome activity is regulated
      through interconversion between the 26 S and 20 S proteasomes induced by
      intracellular calcium mobilization during the meiotic metaphase-anaphase
      transition.

PMID- 7813782
TI  - Mechanism of calcium oscillations in fertilized rabbit eggs.
AB  - Changes in intracellular calcium concentrations ([Ca2+]i) occur at regular
      intervals following fertilization in eggs of all mammalian species studied to
      date. To investigate the mechanisms of their generation, rabbit eggs were
      injected with the fluorescent Ca2+ indicator fura-2 dextran. [Ca2+]i oscillations
      were associated with fertilization (n = 10) and inositol 1,4,5-trisphosphate
      (InsP3;IICR) appears to participate in their generation because injection of
      heparin (100 mg/ml in the pipette), a competitive InsP3 receptor antagonist,
      blocked or considerably delayed the fertilization [Ca2+]i rises in all eggs
      (8/8). Injection of guanosine 5'-0-(2-thiodiphosphate) (GDP beta[S]), a G-protein
      antagonist, which possibly reduced the production of InsP3, also resulted in
      inhibition of [Ca2+]i oscillations (n = 7). Ca2+ injection-induced Ca2+ release
      in fertilized eggs was observed by injection of CaCl2, which evoked intracellular
      Ca2+ release in all oscillating eggs (n = 14), but only in a few late
      fertilization stage nonoscillating eggs (7/19 eggs) and in none of the
      unfertilized eggs (n = 11). Injection of InsP3 (5 microM) between fertilization
      [Ca2+]i rises also elicited Ca2+ responses that were similar in peak [Ca2+]i to
      the fertilization [Ca2+]i rises (n = 5). In unfertilized eggs, injection of
      guanosine 5'-0-(3-thiotriphosphate) (GTP[S]; 5-20 mM), a stimulator of G
      proteins, induced [Ca2+]i oscillations. CaCl2 injections, delivered between
      GTP[S]-induced [Ca2+]i rises, resulted in increased Ca2+ responses in 5/7 eggs.
      The results of this study indicate that IICR participates in the generation of
      fertilization-associated [Ca2+]i rises and that Ca2+ injection-induced Ca2+
      release appears to be stimulated by a product of the phosphoinositide pathway.
      Furthermore, the time to reach threshold levels of InsP3 may dictate the
      periodicity of fertilization [Ca2+]i rises in rabbit eggs.

PMID- 7813783
TI  - Germ cell-specific proteins interact with the 3' untranslated regions of Prm-1
      and Prm-2 mRNA.
AB  - The testis-specific mouse protamine genes (Prm-1 and Prm-2) are transcribed in
      haploid round spermatids, their mRNAs stored as cytoplasmic ribonucleoprotein
      particles and translated about 1 week later in elongating spermatids. We have
      compared the in vitro translational efficiencies of deproteinized Prm-1 mRNA
      isolated from purified populations of germ cells and found that Prm-1 mRNA from
      round spermatids translates as efficiently as Prm-1 mRNA from elongating
      spermatids, suggesting that translation of Prm-1 mRNA is normally repressed in
      round spermatids. Previous studies in transgenic mice have shown that the 3' UTR
      of Prm-1 mRNA is necessary and sufficient for its translational control (Braun et
      al., 1989). In this manuscript, we have used an RNA band shift assay to identify
      an activity, present in cytoplasmic fractions of meiotic spermatocytes and
      postmeiotic round spermatids, that binds the 3'UTRs of both Prm-1 and Prm-2 mRNA.
      We have used 3' UTR deletion variants to map the binding site to a 22-nt region
      within the Prm-1 3' UTR and to a 20-nt region within the Prm-2 3' UTR. uv cross
      linking of the RNA band shift activities detected with the Prm-1 and Prm-2 3'
      UTRs generated the same two RNA/protein complexes of 53 and 55 kDa. The presence
      of the binding activity in the cell type and subcellular compartment associated
      with Prm-1 and Prm-2 mRNA storage suggest that the activity may be actively
      engaged in translational repression of these mRNAs.

PMID- 7813785
TI  - Clonal analysis in the chicken retina reveals tangential dispersion of clonally
      related cells.
AB  - Development of the chicken retina was investigated through clonal analysis using
      retroviral vectors. Replication-incompetent retroviral vectors encoding either
      human placental alkaline phosphatase, beta-galactosidase, or a viral core protein
      were used in paired combinations to infect retinal progenitor cells from
      Embryonic Days 2.5-7.0. Labeled clones were analyzed late in embryonic
      development after retinal histogenesis was complete. The early accessibility of
      the chicken retina, combined with its large final size, resulted in the labeling
      of much larger clones than had been reported previously in other species. The
      clones were composed of many cell types, supporting previous conclusions from
      other vertebrates that the progenitor cells of developing retina are multipotent.
      The majority of clones derived from early infections consisted of multiple
      tightly clustered arrays of cells accompanied by dispersed individual cells.
      Clonal complexity and tangential dispersion were greater in peripheral than
      central retina and decreased considerably with increasing age of infection. These
      observations suggest that early during retinal development, shortly after optic
      cup formation, there is considerable mixing of progenitor cells.

PMID- 7813784
TI  - Expression of a homologue of the deleted in colorectal cancer (DCC) gene in the
      nervous system of developing Xenopus embryos.
AB  - The deleted in colorectal cancer (DCC) gene has been identified as a candidate
      tumor suppressor gene on the basis of frequent allelic loss and decreased or
      absent gene expression in several human cancer types, as well as somatic
      mutations in the gene in colorectal tumors. We have identified a Xenopus DCC
      homologue (XDCC alpha) predicted to encode a protein of 1427 amino acids and have
      characterized XDCC expression in developing embryos and adult tissues. The
      predicted amino acid sequences of XDCC alpha and human DCC are greater than 80%
      identical; each has four immunoglobulin-like domains, six fibronectin type III
      domains, and a cytoplasmic domain of about 325 amino acids. While RNase
      protection assays and immunoblotting studies failed to detect XDCC alpha
      expression in embryos prior to developmental stage 15, XDCC alpha expression was
      present in embryos from stages 19 to 46. Whole mount in situ hybridization
      studies localized XDCC alpha expression to developing forebrain, midbrain, and
      hindbrain regions. DCC expression was inhibited by treatments that altered the
      development of mature neural structures; specifically, uv-ventralized embryos and
      exogastrulae had reduced DCC expression. These results indicate that XDCC alpha
      is developmentally regulated and expressed as a consequence of neural induction.
      Moreover, unlike some well-characterized tumor suppressor genes, such as the p53
      and retinoblastoma genes, that are not differentially expressed in developing
      Xenopus embryos, the DCC gene may have a specific role in the morphogenesis of
      the brain and perhaps other tissues and organs.

PMID- 7813787
TI  - Developmental regulation of a matrix metalloproteinase during regeneration of
      axolotl appendages.
AB  - Removal of specific extracellular matrix (ECM) components has been implicated in
      the initiation of salamander limb regeneration. Remodeling of the ECM at the
      distal stump is necessary for the release of cells that eventually contribute to
      the blastema. Several matrix metalloproteinases (MMPs) have been well
      characterized as important to various physiological and pathological processes,
      such as bone remodeling and tumor invasion. The goal of this study is to identify
      and characterize MMPs that modulate the ECM during appendage regeneration in the
      axolotl Ambystoma mexicanum. By analyzing axolotl tissue extracts using gelatin
      substrate gels, we have identified a 90-kDa gelatinase/collagenase that is
      upregulated within hours after limb amputation. This gelatinase shows a dramatic
      elevation in activity during the dedifferentiation and blastema stages. Its
      activity declines by the palette stage and returns to its basal level by the
      digit stages. The increase in activity of the 90-kDa gelatinase in response to
      amputation is independent of the nerve supply and the wound epithelium but these
      factors affect its subsequent downregulation. In addition to the blastema, the 90
      kDa gelatinase can be detected in the stump at least 4 mm proximal to the
      regenerate. Similar regulation of the 90-kDa gelatinolytic activity is observed
      during tail regeneration and flank would healing. We suggest that this 90-kDa
      gelatinase/collagenase may play a role in the initiation and rapid growth phase
      of axolotl regeneration and wound healing.

PMID- 7813786
TI  - Activation of Xenopus MyoD transcription by members of the MEF2 protein family.
AB  - Members of the MEF2 family of DNA binding proteins interact with a set of AT-rich
      sequences commonly found in the promoters and enhancers of muscle-specific genes.
      We have shown that a MEF2 binding site precisely overlaps the TFIID binding site
      (TATA box) in the Xenopus MyoDa (XMyoDa) promoter and appears to play an
      important role in muscle-specific activity of this promoter. To further
      investigate the potential role of MEF2 in the regulation of XMyoDa transcription,
      we have analyzed the appearance of factors that interact with the XMyoDa
      TATA/MEF2 site during early amphibian development. Proteins that bind
      specifically to this site were present at low levels during early development and
      increased in abundance during gastrulation and neurulation. Two related cDNAs
      were isolated that encode proteins that recognize the XMyoDa TATA motif. Both
      proteins are highly homologous to each other, belong to the MADS (MCM1 agamous
      deficiens SRF) protein family, and are most highly related to the mammalian MEF2A
      gene products. Xenopus MEF2A (XMEF2A) transcripts accumulated preferentially in
      forming somites after the appearance of XMyoD transcripts. Ectopic expression of
      XMEF2A and other members of the MEF2 gene family activated transcription of a
      reporter gene controlled by the XMyoDa promoter. Transcriptional activation of
      the XMyoDa promoter required only the conserved DNA binding domain of XMEF2A and
      was independent of a domain necessary for activity when this factor was bound to
      multiple upstream sites. These results suggest that the XMyoDa promoter can be
      activated by binding of MEF2 to the XMyoDa TATA motif and indicate that MEF2
      dependent transcriptional activation occurs by different mechanisms depending on
      the location of the MEF2 binding site. We suggest that XMEF2 expression in
      myogenic cells contributes to the activation and stabilization of XMyoDa
      transcription during muscle cell differentiation.

PMID- 7813788
TI  - The modifier of variegation modulo gene acts downstream of dorsoventral and HOM-C
      genes and is required for morphogenesis in Drosophila.
AB  - Growing evidence involves chromatin structural flexibility in gene regulation
      during development. modulo is a dominant suppressor of position effect
      variegation, suggesting the participation of its product in the assembly of
      higher order chromatin structures. Here we report the patterns of modulo
      expression and regulation during embryogenesis, analyzed in correlation with
      phenotypical defects resulting from the amorphic mutation of the gene. Zygotic
      expression of modulo depends on the activity of genes which pattern the embryo
      along dorsoventral and anteroposterior axes and specify diversified
      morphogenesis, dorsal and the mesoderm-specific genes twist and snail direct
      modulo expression in the presumptive mesoderm. The homeotic genes Sex combs
      reduced and Ultrabithorax positively regulate the gene in the ectoderm of
      parasegment 2 and abdominal mesoderm, respectively, modulo mutants exhibit
      aberrant morphogenesis of tissues originating from those embryonic primordia
      which normally express the gene, but do not show defect in cell fate
      specification. We propose that down-stream of pattern-forming genes modulo
      controls, via chromatin structural changes, genes critical for the process of
      morphogenesis of several tissue types.

PMID- 7813789
TI  - Expression of TGF-beta s and their receptors during implantation and
      organogenesis of the mouse embryo.
AB  - The spatial and temporal expression of the transforming growth factor beta (TGF
      beta) receptors type III, type II, and two types I (ALK-5 and Tsk 7L) and their
      ligands TGF-beta 1 and TGF-beta 2 in postimplantation mouse development were
      examined using the reverse transcription polymerase chain reaction (RT-PCR), in
      situ hybridization, and immunohistochemistry. With RT-PCR, expression of the
      signaling TGF-beta receptors (types II and ALK-5) was shown to be absent in
      isolated germ layers of 6.0-7.5 days postcoitum (dpc) embryos, whereas the type
      III receptor and Tsk 7L were differentially expressed at these stages. In
      contrast, all TGF-beta receptor types were expressed at these stages in the
      pregnant uterus and decidua. TGF-beta 1 and TGF-beta 2 transcripts were detected
      before gastrulation at 6.5 dpc only in the visceral embryonic endoderm, whereas
      during gastrulation, at 7.5 dpc TGF-beta 1 and TGF-beta 2 mRNA was detected in
      all three germ layers. In situ hybridization and immunohistochemistry of the
      expression of the TGF-beta type II receptor confirmed the data obtained by RT
      PCR. Furthermore, the type II receptor was detected in the extraembryonic
      ectoderm of 7.5 dpc embryos. In the embryo proper, TGF-beta type II receptor
      expression was detected only later in differentiating tissues and developing
      organs, but not in the brain and neural tube. Since the expression of the type II
      receptor may essentially determine whether a cell is able to respond to TGF-beta,
      the results are consistent with the view that TGF-beta s might be implicated in
      embryo implantation and organogenesis, but are not involved in gastrulation of
      the embryo.

PMID- 7813790
TI  - Inhibition of protein kinases after an induced calcium transient causes
      transition of bovine oocytes to embryonic cycles without meiotic completion.
AB  - We have examined the response of bovine oocytes matured in vitro for 24 hr to
      parthenogenic activation using compounds that increase intracellular calcium
      (ionomycin) or inhibit protein phosphorylation (6-dimethylaminopurine, DMAP).
      Treatment with ionomycin alone caused resumption of meiosis (57.8 +/- 7.8%) but
      not pronuclear formation (8.9 +/- 7.3%). DMAP alone did not cause resumption of
      meiosis or pronuclear formation. Sequential treatment with ionomycin (5 microM
      for 4 min) immediately followed by DMAP (1.9 mM for 5 hr) resulted in activation
      that led to pronuclear formation (80.5 +/- 13.1%). Completion of meiosis,
      however, was bypassed as evidenced by only one polar body and one pronucleus
      present in activated parthenogenones. It was necessary to incubate the oocytes
      for at least 3 hr in DMAP to obtain high rates of activation (76.6 +/- 9.8%) and
      development to blastocysts (21.1 +/- 1.5%). Temporal separation of the two
      treatments resulted in a decrease in oocytes with one pronucleus and one polar
      body (uniformly diploid parthenogenones) and an increase in a mixture of diploid
      and haploid parthenogenones since DMAP was capable of causing transition to
      interphase of all chromatin configurations after anaphase commenced and prior to
      metaphase arrest. Parthenotes produced with ionomycin and DMAP that developed to
      the blastocyst stage had high cell numbers (70 to 88 cells) and were able to
      cause extended cycles in 33.3% of recipient cattle after nonsurgical transfer to
      the uterus. Response of the bovine oocyte arrested in metaphase II to different
      activation stimuli was also found to show age-dependent changes in pattern of
      activation response and developmental competence.

PMID- 7813791
TI  - The TTG gene is required to specify epidermal cell fate and cell patterning in
      the Arabidopsis root.
AB  - The control of cell fate was investigated in the root epidermis of Arabidopsis
      thaliana. Two distinct types of differentiated epidermal cells are normally
      present: root-hair-bearing cells and hairless cells. In wild-type Arabidopsis
      roots, epidermal cell fate was found to be correlated with cell position, with
      root-hair cells located over radial walls between cortical cells, and with
      hairless cells located directly over cortical cells. This normal positional
      relationship was absent in ttg (transparent testa glabrous) mutants (lacking
      trichomes, anthocyanins, and seed coat mucilage); epidermal cells in all
      positions differentiate into root-hair cells. The opposite condition was
      generated in roots of transgenic Arabidopsis expressing the maize R (R-Lc) gene
      product (a putative TTG homologue) under the control of a strong promoter
      (CaMV35S), which produced hairless epidermal cells in all positions. In both the
      ttg and R-expressing roots, epidermal cell differentiation was affected at an
      early stage, prior to the onset of cell elongation or root-hair formation. The
      ttg mutations were also associated with abnormalities in the morphology and
      organization of cells within and surrounding the root apical meristem. The
      results indicate that alterations in TTG activity cause developing epidermal
      cells to misinterpret their position and differentiate into inappropriate cell
      types. This suggests that, in wild-type roots, TTG provides, or responds to,
      positional signals to cause differentiating epidermal cells that lie over
      cortical cells to adopt a hairless cell fate.

PMID- 7813792
TI  - A fate map for the 32-cell stage of Rana pipiens.
AB  - A fate map of the progeny derived from all blastomeres of the 32-cell stage
      embryo of the leopard frog Rana pipiens has been generated. Embryos presenting
      regular cleavages were injected into two pairs of blastomeres with fluorescein-
      and Texas red-lysine dextran. By stage 21, embryos were sectioned and the tissue
      distribution of labeled clones was determined. The results of 93 clones were
      pooled to give a fate map which represents the derivation of each tissue from the
      different blastomeres of the 32-cell embryo. The results show that all
      blastomeres give rise to multiple tissues and all tissues are derived from at
      least two, and usually more, pairs of blastomeres. Although there is a general
      tendency for ectoderm to derive from the animal hemisphere, endoderm from the
      vegetal hemisphere, and mesoderm from the equatorial region, the boundaries
      between germ layers are not sharply defined at the 32-cell stage but rather
      appear as a series of overlapping zones. The fate map of R. pipiens is quite
      similar to that of Xenopus laevis but differs in some details that are discussed.
      As in all vertebrates, the R. pipiens fate map is not fully deterministic but
      nevertheless has predictive value in that tissues are populated by the progeny of
      the same blastomeres in different embryos.

PMID- 7813793
TI  - Short upstream sequences associated with the muscle-specific expression of an
      actin gene in ascidian embryos.
AB  - The HrMA4 alpha gene for an embryonic muscle actin of the ascidian Halocynthia
      roretzi is activated at the gastrula stage in differentiating muscle cells
      exclusively. The 5' upstream region close to the transcription start site of
      HrMA4 alpha contains several consensus sequences, which include a TATA box at 
      30, and E-box at -71, a CArG box at -116, and a cluster of three E-boxes between 
      150 and -190. When deletion constructs of this region, fused with the bacterial
      gene for beta-galactosidase (lac-Z), were microinjected into fertilized eggs, the
      reporter gene was expressed in muscle cells of tailbud embryos. Analyses of the
      deletion constructs suggested that the 103-bp upstream region is sufficient for
      the appropriate expression of the gene. However, beta-gal activity was very
      rarely detectable in the case of 82-bp upstream region and no activity was
      detected in the case of 72-bp upstream region. Mutations in the proximal E-box
      sequence did not disturb the muscle-specific expression of the reporter gene.
      These results suggest that rather short sequences between nucleotides -103 and 
      72 from the transcription start site are associated with the specific expression
      of HrMA4 alpha.

PMID- 7813794
TI  - The potential to differentiate epidermis is unequally distributed in the AB
      lineage during early embryonic development in C. elegans.
AB  - In the early Caenorhabditis elegans embryo most of the ectoderm arises from the
      AB blastomere, one of the six founder cells. We report that nonequivalent
      blastomeres are generated at the third division round in the AB lineage. Each AB
      granddaughter divides to produce one cell that has the potential to make abundant
      epidermis and one that instead produces primarily nervous system. This unequal
      distribution of the potential to make epidermis occurs in an AB granddaughter
      that is isolated by laser-ablation of all other cells or during the development
      of an isolated AB blastomere in culture. The fidelity of this event is normally
      masked by a signal from the MS founder cell, which induces mesoderm in particular
      AB descendants. When MS induction is prevented by laser cell-ablation or by a
      mutation in the glp-1 gene, the epidermal fate map of the AB great granddaughters
      becomes left-right symmetrical. Cell lineage analyses demonstrate that, in fact,
      the AB lineage becomes entirely left-right symmetrical in the absence of MS
      induction. This accounts for the extra epidermal cells previously observed in a
      glp-1 mutant. Our results suggest that epidermal differentiation in the nematode
      may be controlled by a cell-autonomous mechanism that differentially allocates
      epidermal potential during AB development and that MS induction generates the
      left-right asymmetry in the fates of AB descendants in part by overriding this
      potential.

PMID- 7813795
TI  - The pregastrula establishment of gene expression pattern in Xenopus embryos:
      requirements for local cell interactions and for protein synthesis.
AB  - Although it has been proposed that mesoderm forms in the marginal zone of the
      amphibian embryo through inductive signaling from vegetal pole cells, the details
      of this process remain to be clarified. To determine when marginal zone cells
      become committed to mesodermal fates, cell contact and protein synthesis
      requirements for early transcriptional responses were analyzed in Xenopus
      blastulae. Marginal zone explants were isolated from embryos at different stages
      and either were cultured untreated, or were dissociated in a medium lacking
      calcium and magnesium ions, or cultured in the presence of cycloheximide. Whereas
      many mesoderm-specific transcripts are efficiently induced by activin in
      dissociated animal pole cells, the same markers were not activated in dissociated
      marginal zone cells, which were isolated from mid or even late blastulae and
      cultured in the absence of exogenous inducers. These observations suggest that
      early specification of mesodermal fates requires cell-cell interactions within
      the marginal zone and that the marginal zone cells are not committed to express
      early mesodermal markers until the late blastula stage. Specification of
      mesodermal fates was also assessed by the ability of marginal zone cells to
      express early mesodermal markers in the absence of protein synthesis. Induction
      of Xlim1, 1A11, and, partially, Xbrachyury transcripts in the marginal zone was
      blocked by cycloheximide treatment through late blastula stages, whereas
      Goosecoid and Xwnt8 mRNAs were expressed in the absence of protein synthesis,
      indicating that these sets of markers are activated in vivo through different
      pathways. These observations demonstrate that determination of mesoderm in the
      marginal zone is a multistep process which occurs during late blastula stages and
      depends on cell-cell contact and protein synthesis.

PMID- 7813796
TI  - Endogenous electrical currents and voltage gradients in Xenopus embryos and the
      consequences of their disruption.
AB  - Starting early in development, the Xenopus embryo maintains an inwardly positive
      transepithelial potential (TEP) across its ectoderm. This "ectodermal battery"
      drives ionic current out of the embryo through low-resistance regions. The
      blastopore represents one such region, as we detected currents leaving this
      region starting at stage 14 (2 microA/cm2) and peaking at stage 22 (100
      microA/cm2). The addition of the epithelial Na(+)-channel blocker, benzamil, to
      the bathing solution reduced these currents to 18% of their previous levels. The
      blastopore current generates an intraembryonic voltage gradient that is most
      negative at the blastopore. Along the rostral-caudal axis on the ventral side of
      the embryo, the gradient averaged 27 +/- 4 mV/mm between the blastopore and a
      point 400-600 microns rostral to the blastopore. Up the flank along the dorsal
      ventral axis, the gradient averaged 40 +/- 11 mV/mm between the blastopore and a
      point 250 microns dorsal. We also found that the anterior neural folds at stage
      17 are sites of small (2 microA/cm2 average) outward current. This current also
      generates a significant internal electrical field. We hypothesized that the steep
      gradients we detected in the Xenopus embryo play a causal role in development. To
      test this, we impaled stage 14-16 embryos with glass microelectrodes filled with
      agarose-gelled saline and passed currents through these electrodes that nulled or
      reversed the endogenous currents through the blastopore. Twenty of 23 embryos
      treated with currents of 100 nA or greater for 9 to 11 hr showed developmental
      abnormalities that were apparent externally. These abnormalities included the
      formation of ventral pigmented bulges, failure of the anterior neural tube to
      close, reduced head development and retarded eye formation, the extrusion of
      cells from the blastopore into the bath, and a failure to form functional cilia.
      Only one of 14 control embryos (those treated with 10 nA or no current) developed
      abnormally. Five embryos were treated with 100 nA of current that augmented the
      endogenous current. One of those exhibited abnormal head development while the
      other 4 appeared normal.

PMID- 7813797
TI  - BDNF supports mammalian chemoafferent neurons in vitro and following peripheral
      target removal in vivo.
AB  - Chemoreceptor neurons innervating the rat carotid body were used as a model
      system to define target regulation of visceral sensory development in fetal and
      newborn animals. In vitro, chemoafferents were selectively supported by coculture
      with the carotid body or by treatment with trkB ligands [brain-derived
      neurotrophic factor (BDNF) and neurotrophin-4], whereas nerve growth factor and
      neurotrophin 3 had no effect. In vivo, chemoafferent neurons died following
      carotid body removal at birth, indicating a predominant role of peripheral,
      rather than central, targets in mediating survival at this stage. However, in the
      absence of target tissues, a large proportion of carotid body afferents could be
      rescued by implants containing BDNF. Moreover, BDNF mRNA was detected in the
      newborn carotid body by reverse transcriptase polymerase chain reaction. These
      data provide the first demonstration that BDNF can substitute for peripheral
      target support of sensory neuron survival in vivo and indicate that trkB ligands
      may be particularly important for development of visceral afferents involved in
      cardiorespiratory control.

PMID- 7813798
TI  - The sequence similarity of the Drosophila suppressor of hairless protein to the
      integrase domain has no functional significance in vivo.
AB  - Suppressor of Hairless [Su(H)] plays an essential role in neurogenesis in
      Drosophila by controlling successive alternative cell fate decisions in the
      developing adult epidermis. Analysis of the predicted amino acid sequence of the
      Su(H) protein revealed a weak similarity to the catalytic domain of a family of
      phage integrases and yeast recombinases. We present here the results of a site
      directed mutagenesis of the integrase-related region of Su(H), which indicate
      that this sequence similarity has no functional significance in vivo. We suggest
      that the JK-RBP protein, encoded by the mouse homologue of Su(H), does not act as
      a recombinase, as originally proposed.

PMID- 7813799
TI  - Induction of kidney epithelial morphogenesis by cells expressing Wnt-1.
AB  - During kidney development, unknown signals derived from the ureteric bud induce
      metanephric mesenchymal cells to differentiate into nephron epithelia. In
      addition to the ureteric bud, a number of other tissues can act as heterologous
      inducers of this process in vitro, including embryonic spinal cord. In this
      report we demonstrate that Wnt-1, a gene that encodes a secreted glycoprotein
      expressed in embryonic spinal cord, is capable of conferring nephron-inducing
      activity to fibroblast cell lines. When cocultured with cells expressing
      exogenous Wnt-1, metanephric mesenchyme differentiated into glomerular and renal
      tubular epithelia. No such effect was observed using control cells. These data
      imply that the ability of embryonic spinal cord to act as an inducer of
      nephrogenesis may result from its production of Wnt-1 protein and suggest that a
      member of the Wnt gene family may be a mediator of renal epithelial morphogenesis
      in vivo.

PMID- 7813801
TI  - Structural roles of the spore coat proteins in Dictyostelium discoideum.
AB  - The integrity of spores formed by mutant strains of Dictyostelium discoideum
      lacking the major spore coat proteins, SP96, SP70, or SP60, was compared to that
      of wild-type strains. Single, double, and triple knock-out strains developed
      normally and produced spores which were indistinguishable from wild-type spores
      by light or electron microscopy. However, the mutant strains were susceptable to
      staining with the lectin, ricin A, which recognizes a galactose-rich
      polysaccharide that is normally hidden by overlying spore coat proteins. The
      intensity of staining with fluorescently labeled ricinA increased as the spore
      coat proteins were incrementally lost. While these results indicate that the
      major outer spore coat proteins are not essential for the construction of a multi
      layered spore coat in Dictyostelium, they show that the spores are more porous
      which might make them at risk to predators before germination.

PMID- 7813800
TI  - Heat shock factor 2-like activity in mouse blastocysts.
AB  - The expression of heat shock genes is induced in all living cells by a series of
      proteotoxic treatments. Heat shock genes are also activated spontaneously during
      different phases of embryonic development. HSP89 alpha and HSC70 are expressed at
      a high level in the mouse blastocyst. A family of factors, called HSFs, are able
      to bind to the promoters of heat shock genes on upstream conserved elements
      (HSEs). HSF1 is unable to bind to HSE sequences in absence of stress. It is
      activated after a stress by post-translational modifications and conformational
      change. HSF2 shows common structural domains with HSF1; however, it is active at
      normal temperatures. Recently we showed the presence of an abundant HSE-binding
      activity in nonshocked blastocysts. We demonstrate here by using polyclonal
      antibodies that HSF2 is the major constituent of this constitutive HSE-binding
      activity. HSF2 might be involved in the control of heat shock gene expression
      during early mammalian embryogenesis.

PMID- 7813802
TI  - Type II diabetes: clinical aspects of molecular biological studies.
AB  - Type II diabetes remains a genetic nightmare. The major problem is identifying
      suitable pedigrees, sib-pairs, and populations for study. Segregation analysis
      data suggest that type II diabetes is likely to be polygenic, although one or
      more major genes could also be involved. This and the high prevalence of diabetes
      affect the strategies for searching for genetic mutations. Linkage analysis in
      classical type II diabetes pedigrees is unlikely to be successful. In addition,
      affected sib-pair analysis is limited because both parents are often affected,
      leading to bilineal inheritance. Sib-pairs with both parents alive are unusual,
      so identity by descent analysis is rarely feasible. Strategies to reduce bilineal
      inheritance by identifying sib-pairs with one known nondiabetic parent or with
      the second sibling having mild subclinical diabetes may be worthwhile.
      Identification of individuals or pedigrees with an unusual phenotype that
      suggests a single gene disorder, such as maturity-onset diabetes of the young,
      will continue to be important, for this allows linkage analysis with markers near
      candidate genes and exclusion mapping of chromosomal regions using highly
      polymorphic markers. Population association studies with candidate genes can
      detect mutations that have a minor role in the majority proportion of diabetic
      subjects, but large numbers are required and great care must be taken to exclude
      ethnic group differences between the diabetic and normoglycemic populations. The
      study of small inbred communities might be helpful because they may have fewer
      diabetogenic genes than outbred populations, and this would increase the power of
      sib-pair and population association studies. Direct screening for mutations in
      candidate genes (with single-strand conformation polymorphism or heteroduplex
      screening or with direct sequencing) in patients with the appropriate
      pathophysiological abnormality can be a successful strategy. The identification
      of well-defined diabetic pedigrees, sib-pairs, and suitable matched diabetic and
      nondiabetic populations will be key to the discovery of the genes for diabetes.

PMID- 7813803
TI  - Function, mass, and replication of porcine and rat islets transplanted into
      diabetic nude mice.
AB  - Well-characterized aliquots of adult porcine and rat islets of comparable beta
      cell mass were transplanted under the kidney capsule of streptozotocin-induced
      diabetic nude mice. In both porcine and rat islet grafts, beta-cell mass
      decreased significantly in the first 2 months and stabilized thereafter. As with
      beta-cell mass, insulin content decreased significantly in the first 2 months to
      almost 40% of that originally implanted. In porcine grafts, however, insulin
      content at 4 months was significantly higher than at 2 months. The endocrine non
      beta-cell mass of grafts also decreased significantly after transplantation: in
      porcine grafts, the decrease was less than in rat and was limited to the first 2
      months. beta-cell replication of engrafted islets was significantly lower in
      porcine than in rat grafts. Although beta-cell mass of porcine and rat grafts was
      similar at all time periods, recipients of porcine islets required a
      significantly longer time to reach normal glucose levels; nonetheless, their
      blood glucose levels continued to decrease and stabilized at levels significantly
      lower than those of normal mice. During oral and intraperitoneal glucose
      tolerance tests, blood glucose increased only slightly in both the recipients of
      porcine and rat grafts. When graft-bearing kidneys were perfused in situ, porcine
      islet grafts showed a 20-fold increase in insulin release in response to both
      glucose and arginine. In conclusion, this evidence that adult porcine islet
      grafts can bring glucose levels to those that are normal for humans provides
      further support of their potential for human islet replacement therapy.

PMID- 7813804
TI  - Retinopathy, glucose, and insulin in an elderly population. The Rotterdam Study.
AB  - We studied the association between retinopathy and glucose metabolism in a
      population-based study of elderly men and women. Glucose metabolism was assessed
      by serum fructosamine and a nonfasting oral glucose tolerance test, and
      retinopathy was evaluated by fundus photography. Retinopathy was present in 296
      of 6,191 subjects examined (4.8%; 120 men and 176 women). Serum glucose and
      fructosamine levels were higher in subjects with retinopathy compared with those
      without (8.4 vs. 6.8 mmol/l and 329.8 vs. 308.5 mumol/l, respectively, P <
      0.001). Two-hour postload insulin levels and insulin resistance, assessed by the
      ratio of postload insulin over postload glucose level, did not differ between the
      two groups. These associations were similar in men and women and in subjects with
      and without diabetes and did not change after adjustment for body mass index or
      systolic blood pressure. Within the group of subjects who had retinopathy, serum
      glucose was significantly associated with the number of hemorrhages. These
      findings suggest that the presence and severity of retinopathy are associated
      with higher serum glucose levels, both in subjects with and without diabetes.

PMID- 7813805
TI  - Accelerated beta-cell destruction in adoptively transferred autoimmune diabetes
      correlates with an increased expression of the genes coding for TNF-alpha and
      granzyme A in the intra-islet infiltrates.
AB  - Autoimmune destruction of beta-cells in nonobese diabetic (NOD) mice is greatly
      accelerated by adoptive cotransfer of syngeneic CD4+ and CD8+ T-cells from
      diabetic animals into newborn NOD mice. We followed, by in situ hybridization,
      the appearance of mRNA of the tumor necrosis factor (TNF)-alpha gene and, as a
      marker for activated cytotoxic T-cells, of the serine protease granzyme A gene in
      the cellular infiltrates generated by cell transfer at birth. Cells expressing
      the genes for granzyme A or TNF-alpha were seen in considerable numbers already
      on day 14, after adoptive transfer. These numbers gradually increased in the
      intra-islet infiltrates from day 14 through day 30 after adoptive transfer.
      Compared with our previous findings in NOD mice developing spontaneous insulin
      dependent diabetes mellitus (IDDM) (Held W, MacDonald HR, Weissman IL, Hess MW,
      Mueller C: Genes encoding tumor necrosis factor alpha and granzyme A are
      expressed during development of autoimmune diabetes. Proc Natl Acad Sci USA
      87:2239-2243, 1990), frequencies of cells with TNF-alpha and granzyme A mRNA were
      2- and 12-fold higher, respectively, in transferred IDDM (trIDDM). TNF-alpha mRNA
      positive cells were predominantly found in the CD4+ T-cell subset of the pancreas
      infiltrating cells, whereas granzyme A mRNA positive cells were mainly observed
      in the CD4- T-cell subset. The effects of the observed enhanced TNF expression
      upon the pathogenesis of trIDDM are as yet unknown.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7813806
TI  - Polymorphic amino acid variations in HLA-DQ are associated with systematic
      physical property changes and occurrence of IDDM. Members of the Swedish
      Childhood Diabetes Study.
AB  - The association between human leukocyte antigen (HLA) and insulin-dependent
      diabetes was studied in a large population-based investigation using genotyping
      of 425 new-onset patients, 0-14 years of age, and 367 matched control subjects.
      As many as 97% of patients compared with 75% of control subjects were positive
      for one or several of DQA1*0301, DQA1*0501, DQB1*0302, or DQB1*0201. Asp-57 DQB
      was present among 28% of patients, indicating that this residue alone does not
      confer protection. Combining Asp-57 DQB1 with either Arg-52 DQA1 or Leu-69 DQA1
      did not explain susceptibility or protection either. DQA1*0301-DQB1*0302 (DQ8)
      and DQA1*0301-DQB1*0301 (DQ7) are identical except for four amino acid
      substitutions in the beta-chain, but DQ8 was positively (odds ratio 8.07; P <
      0.001) and DQ7 negatively (odds ratio 0.38; P < 0.001) associated with the
      disease. Molecular modeling was used to determine whether physiochemical
      properties such as steric factors and surface electrostatic potentials also
      differ in a systematic way for various DQ molecules. Amino acids were substituted
      systematically at the four polymorphic sites, and the solvent-accessible surfaces
      and electrostatic potentials were computed for each molecule. Dramatic
      alterations in electrostatic potential were seen for double substitutions at
      position 45 (G45E) and 57 (A57D) of DQB1. The variation of physicochemical
      properties due to polymorphic substitutions may be significant to the mechanism
      of HLA-DQ association with insulin-dependent diabetes, via the effect these
      property variations have on peptide antigen binding selectivity and subsequent
      interactions with specific T-cell receptors.

PMID- 7813807
TI  - The HOXD8 locus (2q31) is linked to type I diabetes. Interaction with chromosome
      6 and 11 disease susceptibility genes.
AB  - Type I diabetes susceptibility genes have been identified within the major
      histocompatibility complex (MHC) on chromosome 6p21.3 and near the VNTR/insulin
      region on chromosome 11p15.5. We have used polymorphic dinucleotide repeat
      markers to search the human genome for additional susceptibility genes in 162
      type I diabetic families with an affected sibling pair. We report that an
      additional susceptibility gene is located on chromosome 2q31 near HOXD8 (P < 10(
      5), maximum logarithm of odds score = 4.8) in an analysis of affected sibling
      pairs having specific human leukocyte antigen (HLA) and hypervariable nucleotide
      tandem repeat (VNTR)/insulin gene haplotypes (absence of high-risk HLA-DR3/4
      haplotypes and presence of homozygous high-risk class I VNTR alleles). These
      results suggest the interaction of a minimum of three genes in the pathogenesis
      of type I diabetes in humans.

PMID- 7813808
TI  - Reduction of the incretin effect in rats by the glucagon-like peptide 1 receptor
      antagonist exendin (9-39) amide.
AB  - Glucagon-like peptide 1 (7-37)/(7-36) amide (GLP-1) is derived from the
      intestinal proglucagon processing. It is considered an important insulin
      releasing gut hormone. This study uses exendin (9-39) amide as a GLP-1 receptor
      antagonist to evaluate the contribution of GLP-1 to the incretin effect.
      Anesthetized rats were challenged by an intraduodenal glucose infusion to
      evaluate maximally occurring GLP-1 and gastric inhibitory polypeptide (GIP)
      plasma levels. Maximal immunoreactive (IR) GLP-1 plasma levels amounted to 10
      pmol/l (IR-GIP 11 pmol/l). Exendin (9-39) amide abolished the insulin-stimulatory
      effect of 60 pmol of GLP-1 or of the GLP-1 agonist exendin-4 (0.5 nmol) injected
      as bolus, respectively. An intravenous bolus injection of 5.94 nmol of exendin (9
      39) amide 3 min before enteral glucose infusion grossly reduced the total insulin
      secretory response (by 60%) and significantly increased circulating blood glucose
      levels (P < 0.05). In contrast, the GLP-1 antagonist left the insulin response
      after an intravenous glucose or glucose plus GIP (60 pmol) load unaltered. Our
      data support the concept that GLP-1 is an important incretin factor. Exendin (9
      39) amide is a useful GLP-1 antagonist for in vivo studies.

PMID- 7813809
TI  - A role for DNA mutations in diabetes-associated teratogenesis in transgenic
      embryos.
AB  - Congenital malformations are the leading cause of death in infants of insulin
      dependent diabetic mothers. Although there are data to suggest that hyperglycemia
      itself is teratogenic, few mechanisms have been proposed to explain diabetic
      embryopathy. To address the possibility that DNA mutations play a role in the
      fetal malformations associated with diabetes, we developed a transgenic mouse
      model system to measure the mutation frequency of a neutral target gene, lacI,
      during embryonic development in a maternal hyperglycemic environment. Despite the
      short 21-day gestational period of the mouse, we observed a twofold increase in
      the mutant frequency of the lacI transgene in fetuses that developed in a mild
      diabetic environment (blood glucose > 8.3 mmol/l) compared with those that
      developed under normoglycemic conditions (blood glucose < 8.3 mmol/l). These data
      provide the first direct evidence of the genotoxic effect of diabetes in vivo and
      suggest a mechanism for the teratogenicity of the maternal diabetic environment.

PMID- 7813810
TI  - Reduced levels of mRNA encoding endoskeletal and growth-associated proteins in
      sensory ganglia in experimental diabetes.
AB  - This study investigated changes in levels of mRNAs encoding the three
      neurofilament (NF) proteins NF-L (low), NF-M (medium), and NF-H (high) and two
      growth-associated proteins, GAP-43 and T alpha 1 alpha-tubulin, in lumbar dorsal
      root ganglia of control and streptozocin-induced diabetic rats. After 8 weeks of
      diabetes the animals were killed, and total RNA was isolated from the L4 and L5
      dorsal root ganglia and subjected to Northern blotting, with constant amounts of
      total RNA loaded onto each lane. A truncated sense RNA for GAP-43 was included as
      an internal standard during RNA isolation to enable accurate quantification of
      mRNA levels. The filters were probed sequentially with 32P-labeled cDNAs encoding
      NF-L, NF-M, NF-H, GAP-43, T alpha 1 alpha-tubulin, and citrate synthase.
      Hybridizing RNAs were detected by autoradiography and quantified by image
      analysis. Hybridization signals were normalized to those of the internal
      standard. In diabetes, NF-L mRNA levels (2.5- and 4-kilobase [kb] transcripts)
      were decreased by 35 (P = 0.002) and 34% (P < 0.001), respectively, the NF-H mRNA
      level was decreased by 65% (P < 0.001), but the NF-M mRNA remained unchanged. T
      alpha 1 alpha-tubulin and GAP-43 mRNA levels were reduced by 56 (P < 0.001) and
      30% (P < 0.05), respectively. Levels of citrate synthase mRNA were unchanged.
      These data indicate a selective defect of expression of growth-associated and
      endoskeletal proteins in experimentally induced diabetes.

PMID- 7813811
TI  - Gender and insulin sensitivity in the heart and in skeletal muscles. Studies
      using positron emission tomography.
AB  - Good insulin sensitivity is independently associated with a low risk for coronary
      heart disease, but it is unclear whether this risk factor differs between men and
      women. We compared insulin sensitivity of glucose uptake directly in muscle and
      heart tissues between healthy women (age 29 +/- 2 years, body mass index [BMI] 22
      +/- 1 kg/m2, VO2max 39 +/- 4 ml.kg-1.min-1) and men matched for age (31 +/- 2
      years), BMI (23 +/- 1 kg/m2), and VO2max (44 +/- 3 ml.kg-1.min-1) using
      [18F]fluoro-2-deoxy-D-glucose and positron emission tomography under
      hyperinsulinemic (insulin infusion rate 1 mU.kg-1.min-1) normoglycemic
      conditions. Whole body insulin sensitivity was 41% greater in women (52 +/- 6
      mumol.kg body wt-1.min-1) than in men (37 +/- 3 mumol.kg body wt-1.min-1, P <
      0.05). This difference was explained by a 47% greater rate of glucose uptake by
      femoral muscles (113 +/- 10 vs. 77 +/- 7 mumol.kg muscle-1.min-1, women vs. men,
      P < 0.01). Insulin-stimulated glucose uptake rates in the heart were similar in
      women (738 +/- 58) and men (749 +/- 62 mumol.kg muscle-1.min-1). Femoral muscle
      insulin sensitivity was closely correlated with whole body insulin sensitivity (r
      = 0.84, P < 0.001). Gender and VO2max together explained 68% of the variation in
      femoral muscle glucose uptake. We conclude that women are more sensitive to
      insulin than equally fit men because of enhanced muscle but not heart insulin
      sensitivity.

PMID- 7813812
TI  - Determinants of plasminogen activator inhibitor 1 activity in treated NIDDM and
      its relation to a polymorphism in the plasminogen activator inhibitor 1 gene.
AB  - Plasminogen activator inhibitor 1 (PAI-1) activity is increased in patients with
      non-insulin-dependent diabetes mellitus (NIDDM) and may contribute to their
      excess risk of cardiovascular disease. We examined the determinants of PAI-1
      activity in 146 NIDDM subjects by using specific assays of insulin and intact and
      des-31,32-proinsulin and measures of insulin resistance, relating these
      measurements to serum lipids, hypoglycemic therapy, and a common 4G/5G
      polymorphism in the promoter region of the PAI-1 gene. Subjects were treated with
      insulin, sulfonylurea, sulfonylurea plus metformin, metformin, and diet alone. In
      the whole group, PAI-1 activity correlated significantly with serum triglycerides
      (r = 0.39, P < 0.001), specific insulin (r = 0.29, P < 0.001), intact proinsulin
      (r = 0.24, P = 0.004), and des-31,32-proinsulin (r = 0.30, P < 0.001) and in
      subjects not on insulin (n = 110), with insulin sensitivity (r = -0.42, P <
      0.001). There was a significant difference in PAI-1 activity among the three
      genotypic groups (P = 0.016); subjects with the genotype 4G/4G had PAI-1 levels
      one-third higher than those with the 5G/5G genotype. In the 4G/4G group, PAI-1
      activity correlated significantly with triglyceride levels (r = 0.65, P <
      0.0001). There was no significant difference in PAI-1 activity in the different
      treatment groups despite a significant difference in concentrations of intact and
      des-31,32-proinsulin. In a multiple regression model, insulin sensitivity and the
      interaction between PAI-1 4G/5G genotype and triglyceride were the strongest
      determinants of PAI-1 activity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7813813
TI  - Reduced expression of hexokinase II in insulin-resistant diabetes.
AB  - The regulation of hexokinase II (HKII) was examined in fat and skeletal muscle of
      an animal model of non-insulin-dependent diabetes mellitus, the KKAY mouse. These
      tissues require insulin for facilitated transport of glucose and express the
      insulin-responsive transporter GLUT4. The combined data from two experiments (n =
      12 for each experimental condition) demonstrated mean concentrations of plasma
      insulin in pmol/l and glucose in mmol/l of 122 and 7.2 (control nondiabetic C57
      mouse) vs. 1,118 and 29.6 (diabetic mouse), respectively. The tissues of diabetic
      mice compared with control mice demonstrated a reduction of HKII mRNA abundance
      of 68% in epididymal fat (P = 0.0001) and 34% in the quadriceps muscles (P <
      0.001), with concordant reduction in the abundance of GLUT4 mRNA of 60% in
      epididymal fat (P < 0.001). In comparison with the results in untreated diabetic
      mice, diabetic animals treated with the insulin-sensitizing drug pioglitazone
      demonstrated an increase in the abundance of HKII mRNA with a concordant increase
      of GLUT4 mRNA in epididymal fat (P = 0.03 and < 0.01, respectively), and an
      increase of HKII mRNA in the quadriceps muscles (P < 0.05). Separate experiments
      demonstrated a reduction of HKII protein abundance by 61% in epididymal fat (P <
      0.001, n = 12 for each experimental condition) and by 71% in the quadriceps
      muscles (P < 0.001, n = 6 for each experimental condition). In comparison with
      untreated diabetic mice, there was an increase in the abundance of HKII protein
      in epididymal fat of animals treated with pioglitazone (P < 0.05).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7813814
TI  - Induction of insulitis in athymic (nude) mice. The effect of NOD thymus and
      pancreas transplantation.
AB  - The NOD mouse is a model for human insulin-dependent diabetes mellitus. The
      disease is thought to have an autoimmune etiology because it is T-cell dependent
      and is characterized by mononuclear cell infiltration in and around the
      pancreatic islets of Langerhans. The mechanism by which autoreactive T-cells are
      generated is not fully understood, but it has been postulated that there is a
      breakdown in self-tolerance induction during intrathymic T-cell maturation. The
      aim of these studies was to determine whether transplantation of NOD thymus into
      diabetes-resistant mouse strains would generate islet-reactive T-cells. Neonatal
      thymus was pretreated either by irradiation or culture in 2-deoxyguanosine (dGua)
      and then transplanted into athymic BALB/c, CBA, and C57BL/6 nude mice. Generally,
      insulitis was not seen in the CBA or C57BL/6 recipients, but was found in 56% of
      BALB/c mice transplanted with an irradiated NOD thymus and in 46% BALB/c mice
      with a dGua-treated thymus. Similar experiments in which a NOD fetal pancreas was
      transplanted into nude BALB/c mice before NOD thymus transplantation showed a
      similar frequency and severity of insulitis in both the host pancreas and grafted
      NOD pancreas. This suggests that NOD islets are no more prone than the host
      islets to autoimmune attack and do not exacerbate insulitis. Overall, the data
      suggest that a defect of thymic origin (and correlating with the thymic
      epithelium) in the NOD mouse can lead to the development of autoreactive T-cells
      and specific islet cell damage. Autoreactivity appears to be restricted to the H
      2Kd allele that is shared by NOD and BALB/c mice.

PMID- 7813815
TI  - Autoantibodies against oxidatively modified low-density lipoproteins in NIDDM.
AB  - Diabetes is an independent risk factor in the development of atherosclerosis,
      although the pathophysiological processes underlying this association are poorly
      understood. The oxidation of low-density lipoprotein (LDL) is considered a key
      event in the development and progression of atherosclerosis because it generates
      molecular epitopes that are more atherogenic than parent LDL. A total of 138
      patients suffering from non-insulin-dependent diabetes mellitus (NIDDM) and 80
      matched control subjects were investigated. LDL oxidation was evaluated as the
      presence of autoantibodies against oxidatively modified LDL, since they mirror
      the in vivo occurrence of oxidative processes. NIDDM patients had an antibody
      ratio (calculated as the ratio of antibodies against modified versus native LDL)
      significantly higher than control subjects for Cu(2+)-oxidized LDL (1.88 +/- 0.6
      vs. 1.05 +/- 0.3, P < 0.01, for IgG), malondialdehyde-modified LDL (2.54 +/- 0.73
      vs. 2.04 +/- 0.11, P < 0.01, for IgG and 3.96 +/- 1.51 vs. 2.90 +/- 0.15, P <
      0.01, for IgM), and malondialdehyde-modified human serum albumin (1.79 +/- 0.54
      vs. 1.46 +/- 0.1, P < 0.05 for IgG). The possible role played by glycation in
      sensitizing LDL to oxidation was investigated by measuring autoantibodies against
      both glycated LDL (glycLDL) and glycoxydated LDL (glycoxLDL). NIDDM patients had
      an antibody ratio significantly higher than control subjects for anti-glycLDL and
      anti-glycoxLDL IgG (1.79 +/- 0.38 vs. 1.12 +/- 0.23, P < 0.01 and 2.55 +/- 1.03
      vs. 1.39 +/- 0.44, P < 0.01, respectively) but not anti-glycLDL and anti-glycox
      LDL IgM.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7813816
TI  - A novel insulin secretagogue is a phosphodiesterase inhibitor.
AB  - The arylpiperazine L-686,398 was described as an oral hypoglycemic agent and is
      shown to be an insulin secretagogue in vitro. The characteristics of its activity
      were similar to those of the incretin glucagon-like peptide I (GLP-I). We
      demonstrate that both the peptide and L-686,398 increase the accumulation of cAMP
      in isolated ob/ob mouse pancreatic islet cells, but by different mechanisms.
      Although GLP-I activates adenylate cyclase, the arylpiperazine has no effect on
      this enzyme or on the binding of 125I-labeled GLP-I to its receptor on RINm5F rat
      insulinoma cell membranes. However, L-686,398 inhibits the total cAMP
      phosphodiesterase (PDE) activity in homogenates of ob/ob mouse pancreatic islets
      with an EC50 of approximately 50 mumol/l. To determine the mechanism of PDE
      inhibition by the arylpiperazine and to examine its specificity, we studied the
      kinetics of arylpiperazine inhibition of two recombinant PDEs. The arylpiperazine
      is a competitive inhibitor of both a human heart type III PDE and a rat type IV-D
      PDE. Inhibition of the type III and IV isozymes are characterized by Ki values of
      27 and 5 mumol/l, respectively. Although not extremely potent, the arylpiperazine
      does exhibit modest selectivity between these PDEs. The observation that L
      686,398 acts as a PDE inhibitor suggests that exploration for beta-cell-specific
      PDE isoforms may reveal novel PDEs as targets for the development of
      therapeutically useful glucose-dependent insulin secretagogues.

PMID- 7813818
TI  - Tissue factor pathway inhibitor activity in patients with IDDM.
AB  - Until now, several endothelium-dependent hemostatic parameters have been proposed
      as markers of vascular endothelial dysfunction in diabetes. We studied tissue
      factor pathway inhibitor (TFPI) activity in insulin-dependent diabetes mellitus
      (IDDM) patients without macro-or microvascular complications, before and after
      intravenous administration of heparin, in comparison with age-matched control
      subjects. We also examined the effect of acute hyperglycemia on TFPI activity in
      healthy men. A clotting and a chromogenic assay were used for determining TFPI
      activity. In the clotting assay, the COOH-terminus of TFPI is essential, but in
      the chromogenic assay, it is of minor importance. When the chromogenic assay was
      used, TFPI activity before heparin injection was significantly higher in the IDDM
      patients (92 +/- 24 vs. 112 +/- 23%, P < 0.01). The postheparin increase in TFPI
      activity, measured with both assays, was significantly higher in the diabetic
      subjects (area under the curve: clotting assay 64 +/- 14 vs. 81 +/- 24, P < 0.05;
      chromogenic assay 82 +/- 26 vs. 121 +/- 35, P < 0.0001). A positive correlation
      between TFPI activity and glycated hemoglobin was demonstrated. Acute
      hyperglycemia did not alter TFPI activity. It can be concluded that TFPI
      activity, especially after stimulation with heparin, is affected by chronic
      hyperglycemia in diabetic subjects without vascular complications. Alterations in
      TFPI activity may therefore reflect early endothelial dysfunction.

PMID- 7813817
TI  - Loss of glucose-induced insulin secretion and GLUT2 expression in transplanted
      beta-cells.
AB  - Either 200 or 400 syngeneic islets were transplanted under the kidney capsule of
      normal or streptozocin-induced diabetic B6/AF1 mice. The diabetic mice with 400
      islets became normoglycemic, but those with 200 islets, an insufficient number,
      were still diabetic after the transplantation (Tx). Two weeks after Tx, GLUT2
      expression in the islet grafts was evaluated by immunofluorescence and Western
      blots, and graft function was examined by perfusion of the graft-bearing kidney.
      Immunofluorescence for GLUT2 was dramatically reduced in the beta-cells of grafts
      with 200 islets exposed to hyperglycemia. However, it was plentiful in grafts
      with 400 islets in a normoglycemic environment. Densitometric analysis of Western
      blots on graft homogenates demonstrated that GLUT2 protein levels in the islets,
      when exposed to chronic hyperglycemia for 2 weeks, were decreased to 16% of those
      of normal recipients. Moreover, these grafts had defective glucose-induced
      insulin secretion, while the effects of arginine were preserved. We conclude that
      GLUT2 expression in normal beta-cells is promptly down-regulated during exposure
      to hyperglycemia and may contribute to the loss of glucose-induced secretion of
      diabetes.

PMID- 7813819
TI  - Somatostatin selectively couples to G(o) alpha in HIT-T15 cells.
AB  - Previously, we have demonstrated that somatostatin mediates all of its inhibitory
      effects on glucose-induced insulin secretion from the HIT-T15 cell through
      pertussis toxin-sensitive G-proteins and that the membrane fraction of this
      clonal line of pancreatic beta-cells contains six such proteins: G(i) alpha 1,
      G(i) alpha 2, G(i) alpha 3, and three forms of G(o) alpha. To determine the
      specificity of somatostatin receptor-G-protein coupling in HIT-T15 cells, we
      examined the ability of antisera specific for the COOH-terminus of G alpha
      subtypes to inhibit somatostatin-induced augmentation of membrane GTPase
      activity. GTPase activity increased in membranes as a function of GTP. At all
      concentrations of GTP studied, 1 mumol/l somatostatin stimulated GTPase activity.
      Pertussis-toxin pretreatment prevented the effects of somatostatin. Antisera
      selective for G(o) alpha subtypes reduced the effects of somatostatin on GTPase
      activity (GTPase activity in absence of antisera, 125 +/- 3% of control; in the
      presence of antisera 976, 110 +/- 2% of control; n = 13, P < 0.001), whereas
      antisera directed against G(i) alpha 1, G(i) alpha 2, G(i) alpha 3, and Gs alpha
      were without effect. Somatostatin also significantly prevented cyclic AMP
      accumulation during perifusion with 11.1 mmol/l glucose through a pertussis toxin
      sensitive mechanism. These data indicate that the somatostatin receptor couples
      to G(o) alpha in the HIT-T15 cell and suggest that G(o) alpha may link
      somatostatin to cyclic AMP metabolism in pancreatic beta-cells.

PMID- 7813821
TI  - Comparison of early communicative behavior in young children with cochlear
      implants and with hearing aids.
AB  - Analysis of preverbal behaviors, which are the natural precursors of language
      development, was performed in three groups of young children with severe/profound
      hearing impairments, based on video recordings of interactions with a known
      adult. All groups were matched for age at assessment. One group of nine children
      had Nucleus multichannel cochlear implants with the MSP sound processor, whereas
      the other two groups of nine children each used conventional hearing aids. The
      first hearing aid group had unaided hearing threshold levels averaging 101 dB and
      were proficient users; the second aided group had hearing threshold levels
      averaging 114 dB and were poor users. Over the assessment period lasting 12 mo,
      starting at implantation or entry to nursery school according to group,
      implantees and proficient hearing aid users developed a strongly vocal/auditory
      style of communicative behavior, especially the implantees. This contrasted with
      a strongly visual/gestural style developed by the poor hearing aid users. It is
      concluded that implantees develop their early communicative behavior along lines
      that are similar to proficient hearing aid users, but more rapidly and more
      strongly in the vocal/auditory direction.

PMID- 7813820
TI  - Cloning of a human insulin-stimulated protein kinase (ISPK-1) gene and analysis
      of coding regions and mRNA levels of the ISPK-1 and the protein phosphatase-1
      genes in muscle from NIDDM patients.
AB  - Complementary DNA encoding three catalytic subunits of protein phosphatase 1 (PP1
      alpha, PP1 beta, and PP1 gamma) and the insulin-stimulated protein kinase 1 (ISPK
      1) was analyzed for variations in the coding regions related to insulin-resistant
      glycogen synthesis in skeletal muscle of 30 patients with non-insulin-dependent
      diabetes mellitus (NIDDM). The human ISPK-1 cDNA was cloned from T-cell leukemia
      and placental cDNA libraries and mapped to the short arm of the human X
      chromosome. Single-strand conformation polymorphism (SSCP) analysis identified a
      total of six variations in the coding regions of the PP1 genes: two in PP1 alpha
      at codons 90 and 255; one in PP1 beta at codon 67; and three in PP1 gamma at
      codons 11,269, and 273, respectively. All were, however, silent single nucleotide
      substitutions. SSCP analysis of the ISPK-1 gene identified one silent
      polymorphism at codon 266 and one amino acid variant at codon 38 (Ile-->Ser).
      This variant was primarily found in one male NIDDM patient. This subject,
      however, did not exhibit an impairment of muscle insulin-stimulated glycogen
      synthase activation. No significant differences were found in mRNA levels in
      muscle of the four genes between 15 NIDDM patients and 14 healthy subjects. Our
      findings suggest that 1) genetic abnormalities in the coding regions of PP1
      alpha, PP1 beta, PP1 gamma, and ISPK-1 are unlikely to be frequently occurring
      causes of the reduced insulin-stimulated activation of the glycogen synthesis in
      muscle from the analyzed group of NIDDM patients; 2) the mRNA levels of PP1
      alpha, PP1 beta, PP1 gamma, and ISPK-1 are normal in muscle from the NIDDM
      patients; and 3) putative inherited defects in insulin-stimulated activation of
      muscle glycogen synthesis in patients with insulin-resistant NIDDM may be located
      further upstream of ISPK-1 in the insulin action cascade.

PMID- 7813822
TI  - Comparative effectiveness of correction strategies in connected discourse
      tracking.
AB  - The effectiveness of four correction strategies commonly used in connected
      discourse tracking was investigated in the present study. The strategies were 1)
      verbatim repetition of a word or phrase; 2) use of antonyms or synonyms as cues;
      3) use of phonemic cues, with no whole word repetition; and 4) going back or
      ahead in the text, with no repetition of the missed segment. Four normal-hearing
      adults served as listeners. Live-voice presentation of text by two female talkers
      was employed for all conditions. Listeners were tested in two stimulus
      presentation modes, speechreading alone and speechreading plus a multichannel
      tactile aid. Results indicated that strategy 1, repetition of the missed segment,
      produced the highest tracking rates, significantly higher than any of the other
      strategies. Strategy 2 produced the lowest tracking rates. Strategies 1 and 3
      yielded the lowest percentage of initially missed words, or blockages, and
      strategy 4 the highest percentage. Significantly higher tracking rates were found
      under the speechreading plus tactile aid presentation mode, compared with
      speechreading alone. Further, tracking rates increased significantly from the
      beginning to the end of training. Data were compared with a more typical CDT
      task, in which all correction strategies were operative, and results showed
      little difference in tracking rates between this task and the constrained CDT
      employing only strategy 1. Overall, results suggest that simple repetition of
      missed segments is an effective correction strategy for CDT and argue for its
      inclusion in computer-assisted tracking implementations.

PMID- 7813823
TI  - The objective assessment of transient evoked otoacoustic emissions in neonates.
AB  - OBJECTIVE: To develop a simple objective method for assessing the presence or
      absence of a TEOAE in recordings from neonatal ears. DESIGN: Several simple,
      objective methods of transient evoked otoacoustic emissions (TEOAE) assessment
      were tested against a verified subjective assessment method, using 200 neonatal
      TEOAEs recorded under clinical conditions. RESULTS: Total TEOAE level did not
      correlate well with the subjective assessment. Total estimated signal to noise
      ratio correlated better with the subjective assessment. Filtering the response
      between 1.5 and 2.8 kHz and windowing it between 4 and 10 msec did not degrade
      the correlation. In a normal population of neonates the filterd, windowed
      estimated signal to noise ratio method miscategorized only 4.0% of the responses
      as having no TEOAEs. None of the population without TEOAEs were categorized as
      having TEOAEs by the objective test. CONCLUSIONS: An objective TEOAE assessment
      (based on the signal to noise ratio of a time limited midband section of the
      TEOAE) performed well at detecting the presence or absence of a TEOAE.

PMID- 7813824
TI  - Quantitative assessment of methods for the detection of otoacoustic emissions.
AB  - OBJECTIVE: To compare the performance of various types of signal detector
      commonly used to detect otoacoustic emissions (OAEs). METHOD: The signal
      detectors were tested with signals in various types of noise, including noise
      with various amplitude distributions. Commonly utilized transient evoked OAE and
      distortion product OAE detectors were analyzed. RESULTS: In both cases it was
      found that detector performance increased as the measurement bandwidth was
      increased. Noises of different amplitude distributions were found to affect the
      performance of both types of detectors. The effect of different amplitude
      distributions decreased as the measurement bandwidth was increased. For a given
      power per spectral line, the transient evoked OAE detector could detect signals 6
      dB farther into gaussian noise than the distortion product OAE detector.
      CONCLUSIONS: An analysis of the results of practical methods of OAE measurement
      show that distortion product OAEs can be measured with higher power per spectral
      line than transient evoked OAEs. This means that in adult humans distortion
      product OAEs can be reliably detected in about 1/14th of the time of transient
      evoked OAEs. In neonatal humans distortion product OAEs can be reliably detected
      in about two-thirds of the time of transient evoked OAEs.

PMID- 7813825
TI  - Three-channel Lissajous' trajectory of human middle latency auditory evoked
      potentials.
AB  - OBJECTIVE: We provide the normative values for middle latency auditory evoked
      potentials (MLAEPs) measures (three-channel Lissajous' trajectories or 3-CLT) in
      response to clicks and tone pips, which are the stimuli most widely used in MLAEP
      clinical testing. The relationship of 3-CLT measures to the more widely used
      latency and amplitude characteristics of the single-channel MLAEP of the same
      subjects was also evaluated. We further relate the 3-CLT findings to the question
      of MLAEP generators. DESIGN: 3-CLT of MLAEPs were derived from 12 humans (24
      ears) in response to 65 dB nHL, rarefaction clicks as well as tone pips (1000
      Hz), presented at a rate of 3.3/sec. A normative set of 3-CLT measures was
      calculated and compared with the corresponding measures of simultaneously
      recorded, single-channel vertex-left mastoid and vertex-neck derivation of MLAEP.
      RESULTS: Apex latencies of 3-CLT were comparable to peak latencies of the vertex
      neck record, both in absolute values and in intersubject variability. Durations
      of planar segments were approximately 5.0 msec. Size and shape measures of planar
      segments were variable across subjects, making their clinical use, in their
      present form, questionable. CONCLUSIONS: The results showed two apices and
      associated planar segments (i1 and i2) in the 3-CLT of MLAEP which corresponded
      to the vertex-neck component Pa. These results and earlier studies that indicated
      a dual set of generators for Pa are compatible with a primary auditory cortex
      generator for i1 and ascending subcortical generators for i2.

PMID- 7813826
TI  - Cochlear implants for congenitally deaf adolescents: is open-set speech
      perception a realistic expectation?
AB  - The prognosis for benefit from use of cochlear implants in congenitally deaf
      adolescents, who have a long duration of profound deafness prior to implantation,
      has typically been low. Speech perception results for two congenitally deaf
      patients implanted as adolescents at the University of Melbourne/Royal Victorian
      Eye and Ear Hospital Clinic show that, after 12 months of experience, both
      patients had significant open-set speech discrimination scores without
      lipreading. These results suggest that although benefits may in general be low
      for congenitally deaf adolescents, individuals may attain significant benefits to
      speech perception after a short period of experience. Prospective patients from
      this group should therefore be considered on an individual basis with regard to
      prognosis for benefit from cochlear implantation.

PMID- 7813827
TI  - Occlusive silence duration of voiceless intervocalic plosives and voicing
      perception by normal and hearing-impaired subjects.
AB  - OBJECTIVE: The duration of occlusive silence of intervocalic unvoiced plosives is
      one of several acoustic cues contributing to the correct identification of
      voicelessness for normally hearing subjects. In a previous investigation on one
      velar plosive, some hearing-impaired subjects required an abnormally long
      duration of its occlusive silence in order to avoid voicing confusions. The
      present study investigated whether this would occur for the different plosives in
      various intervocalic contexts and for male and female voices. DESIGN: Speech
      signals from a male and a female voice pronouncing the three voiceless plosives
      (p,t,k) in three different vocalic contexts (a,i,u) were recorded. Each of these
      18 vowel-consonant-vowel (VCV) utterances was edited to obtain a series of tokens
      with occlusive silence durations varying from 0 to 180 msec. Phonetic
      identification of these tokens was assessed for seven normally hearing persons
      and for seven subjects with a sensorineural hearing loss. RESULTS: For the
      various VCVs, about half of the hearing impaired subjects required abnormally
      long occlusive silence durations to avoid voicing confusions. For normal as well
      as hearing-impaired subjects duration thresholds varied considerably and not
      systematically for the different VCVs. The amount of voicing confusions tended to
      be related to audiogram loss. CONCLUSIONS: For hearing-impaired subjects, a
      normal occlusive silence duration can lead to voicing misperceptions for the
      various plosives in different vowel contexts and for male and female voices. The
      large variability in the results of each subject for the different VCVs indicates
      that even a strong anomaly in temporal perception, which certainly underlies a
      need for abnormally long occlusive silence duration, did not systematically
      overrule voicing perception.

PMID- 7813829
TI  - [The adrenal cortical function of 6-year-old children living in a region polluted
      by the wastes from chemical manufacture].

PMID- 7813828
TI  - [The function of the cardiovascular and endocrine systems of children living in
      areas of radioactive contamination].

PMID- 7813830
TI  - [Vitamin E and the aerobic work capacity of athletes under normo- and
      hyperthermia].

PMID- 7813831
TI  - [Cellular reaction in ethnically and ecologically different human populations].

PMID- 7813832
TI  - [The characteristics of the distribution of blood calcium in a population of St.
      Petersburg inhabitants].

PMID- 7813833
TI  - [The effect of ecological and physiological factors on the composition and
      properties of transport forms of lipids].

PMID- 7813834
TI  - [The rheological properties of gastric mucus during its interdigestive
      secretion].

PMID- 7813836
TI  - [The electroencephalographic and neuropsychological analyses of cerebral
      hemispheric interaction during recovery following craniocerebral trauma].

PMID- 7813837
TI  - [The H-reflex in physiological and medical research].

PMID- 7813835
TI  - [Altered mental states during physiological labor (the formulation of the
      problem)].

PMID- 7813838
TI  - [A method for recording the dynamic indices of the heart rhythm and the
      potentials for its use in sleep research].

PMID- 7813839
TI  - [Hearing deprivation in otosclerosis].

PMID- 7813840
TI  - [The effect of breath-hold deep diving on the biochemical systems of body energy
      support in athletes].

PMID- 7813841
TI  - [Changes in the erythrocytes during physical loading].

PMID- 7813842
TI  - [Changes in the indices of the thrombelastogram at different phases of monthly
      rhythms].

PMID- 7813843
TI  - [The use of the asymmetry of superslow physiological processes for research on
      the level of mental disorders].

PMID- 7813845
TI  - [The effect of lateralized photostimulation on the dynamics of interhemispheric
      asymmetry].

PMID- 7813844
TI  - [Methodological approaches to a psychophysiological basis for the possibilities
      of correcting emotional disorders by a dynamic acoustic-wave field in the mode of
      super-slow physiological processes].

PMID- 7813846
TI  - [The dynamic correlations between the current frequencies of the impulse activity
      of neuronal populations in the human brain in the odd-ball test].

PMID- 7813847
TI  - [The assessment of the status of drug abusers by the indices of oculomotor
      activity and visual motor coordination].

PMID- 7813848
TI  - [The asymmetry of the electrodermal activity of the palms during relaxation
      induced by lateralized electrostimulation of the head].

PMID- 7813849
TI  - [The individual characteristics of operator activity during work under
      psychoemotional tension].

PMID- 7813850
TI  - [The dynamics of operator functional status while working with a varying quality
      of video display frames].

PMID- 7813851
TI  - [A view of adaptation from the position of Markov processes].

PMID- 7813852
TI  - [The mechanisms of circulatory hypoxia in myocardial infarct].

PMID- 7813853
TI  - [The functional activity of the heart and the red blood picture in alcoholic
      intoxication in an ecologically detrimental background].

PMID- 7813854
TI  - [Which classification for chronic hepatitis? Lessons from the hepatitis C virus.
      Groupe Metavir].

PMID- 7813855
TI  - [Relationships between plasma concentrations of endothelin and the severity of
      liver cirrhosis].
AB  - OBJECTIVES: Results of studies on plasma endothelin concentrations in patients
      with cirrhosis are conflicting. Moreover, the relationships between plasma
      endothelin concentrations and the severity of cirrhosis have not yet been
      studied. The aim of this study was to measure plasma endothelin concentrations in
      controls and in patients with cirrhosis. In addition, this study examined the
      relationships between plasma endothelin concentrations, and the severity of liver
      disease, splanchnic and systemic hemodynamics. METHODS: Plasma endothelin
      concentrations (in the hepatic vein and the right atria), hepatic venous
      pressures, arterial pressure, cardiac output, pulmonary pressures and plasma
      concentrations of sodium and creatinine were measured in 7 controls and 28
      patients with cirrhosis. RESULTS: Plasma endothelin concentrations in the hepatic
      vein and the right atria were significantly higher in patients with cirrhosis
      (18.9 +/- 2.9 and 20.2 +/- 3.1 pg/mL, respectively) than in controls (6.1 +/- 1.1
      and 7.2 +/- 1.1 pg/mL, respectively). In these patients, hepatic venous plasma
      endothelin concentrations were significantly correlated with Pugh's score (r =
      0.49), hepatic venous pressure gradient (r = -0.44), and plasma sodium
      concentrations (r = -0.46). No significant correlation was found between plasma
      endothelin concentrations and systemic hemodynamics. CONCLUSION: Plasma
      endothelin concentrations are increased in patients with cirrhosis. Moreover,
      this increase is more marked in patients with severe liver disease than in
      patients with no or moderate impairment of liver function.

PMID- 7813856
TI  - [Hepatic and biliary involvements in systemic diseases].

PMID- 7813857
TI  - [Digestive tract and scleroderma. An update of information].

PMID- 7813858
TI  - [Autoimmune hepatitis. New pathophysiological and clinical aspects].

PMID- 7813859
TI  - [Autoantibodies in digestive and hepatic pathology].

PMID- 7813860
TI  - [Surgical treatment of hemorrhagic rectocolitis. Evolution of indications.
      Evaluation of practices and results].

PMID- 7813861
TI  - [Secretion of peptide YY and truncated glucagon-like peptide 1 by isolated
      intestinal cells in rats].
AB  - In order to study the cellular mechanisms involved in peptide YY (PYY) and
      truncated glucagon-like peptide 1 (TGLP1) release, a model of rat intestinal
      cells dispersed with collagenase/EDTA and enriched for L-cells by counterflow
      elutriation was developed. Elutriation significantly increased in the harvested
      cells the concentration of PYY (828 +/- 97 vs 151 +/- 16 fmol/10(6) cells) and
      TGLP1 (1,094 +/- 109 vs 167 +/- 20 fmol/10(6) cells), and brought the
      contribution of L-cells to 4-5% of the total cell population. Forskolin (1-10
      microM) and dibutyryl cyclic AMP (dbcAMP, 1-5 mM) increased over an 1-h period
      PYY and TGLP1 secretion, with a maximal rate at 5 microM forskolin (232% and 250%
      of basal, respectively) and at 5 mM dbcAMP (347% and 234% of basal,
      respectively). Furthermore, 3-isobutylmethyl xanthine (IBMX, 1 mM) increased PYY
      (226% of basal) and TGLP1 (198% of basal) secretion. A combination of both 10
      microM forskolin and 1 mM IBMX stimulated in an additive manner PYY (389% of
      basal) and TGLP1 (393% of basal) secretion. TPA (12-0-tetradecanoylphorbol-13
      acetate, 0.1-1 microM) dose-dependently increased the secretion of PYY and TGLP1
      (maximal release at 328% and 326%, respectively), whereas 4 alpha-phorbol was
      ineffective. Ionomycin (1-5 microM) and thapsigargin (0.1-5 microM) produced a
      dose-dependent increase in PYY and TGLP1 release (272% and 337% of basal for 5
      microM ionomycin; 342% and 339% of basal for 5 microM thapsigargin,
      respectively). At gel chromatography, the immunoreactive PYY and TGLP1 material
      in cell extracts and in release medium co-eluted with the respective synthetic
      peptides.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7813862
TI  - [Prognostic factors in colorectal adenocarcinoma of Dukes stage B. Study of a
      series of population].
AB  - A study of prognostic factors in Dukes B colorectal adenocarcinoma was performed
      on a population basis in order to determine subgroups with poor prognosis which
      could benefit from adjuvant therapy after surgery. The study considered the 746
      cases of Dukes B colorectal carcinoma diagnosed during the 1976-1988 period among
      Cote-d'Or residents (Burgundy, France). The overall 5-year crude survival rate
      was 55.7%, the corresponding relative survival rate being 73%. In the final Cox
      model, age, tumour extension to adjacent organs, number of examined lymph nodes
      and tumour size were significant prognostic factors. The corresponding
      multivariate relative survival model considered only tumour extension and number
      of examined lymph nodes as having a prognostic value. The relative risk of death
      was 2.3 (range: 1.5-3.3) in case of a tumor extension and 2.5 (range: 1.5-4.4)
      when no lymph node was found compared to surgical samples with at least 6 lymph
      nodes. These data should be taken into account when conceiving or analyzing
      future therapeutic trials.

PMID- 7813863
TI  - [Results of ileoanal anastomosis with mucosectomy and "J" pouch in hemorrhagic
      rectocolitis].
AB  - The aim of this study was to assess the results of ileal "J" pouch-anal
      anastomosis in ulcerative colitis. One hundred and fifty six patients operated on
      between 1983 and 1991 for ulcerative colitis were followed-up prospectively since
      the surgical procedure with a mean of 29 +/- 16 months (range: 6 to 92 months).
      There was no postoperative death. Forty-four patients (28%) presented 48 post
      operative complications and 14 (9%) were reoperated. Twenty-five patients (16%)
      were reoperated because of a late complication. Three pouches had to be removed
      for untreatable fistulas which appeared to be related to a Crohn's disease in 2
      cases; the reestablishment of a diverting loop ileostomy was mandatory in 2
      further patients for anoperineal sepsis. The mean stool frequency at 1 year was
      4.5 +/- 1.9; 40% of patients did not have nocturnal stooling. Daytime and
      nighttime continence were normal in 90.7% and 77.5% of cases respectively, 87% of
      patients considered their social life improved by the surgical cure of the
      disease. The results observed 5 years after the surgical procedure in 37 patients
      were similar to those observed at 1 year. Twenty-five patients (16%) presented
      one or several episodes of pouchitis, including 5 cases of chronic pouchitis. It
      is concluded that the treatment of ulcrerative colitis, ileal "J" pouch-anal
      anastomosis, is a safe and effective procedure which provides good functional
      results.

PMID- 7813864
TI  - [Ileo-anal anastomosis in hemorrhagic-ulcerative rectocolitis and familial
      adenomatous polyposis: is it mandatory to perform resection of the endo-anal
      mucosa?].
AB  - The aim of this study was to assess the clinical outcome after ileal pouch-anal
      anastomosis with mucosectomy for ulcerative colitis and for familial adenomatous
      polyposis, and to characterize the histology of the stripped endoanal mucosa with
      particular reference to the ulcerative colitis activity, adenomatous polyps and
      dysplasia. Twenty-eight patients were operated, 16 for ulcerative colitis (group
      I) and 12 for familial adenomatous polyposis (group II). In group I, there were
      no intraoperative complications, but mucosectomy was tedious in 10 patients (62%)
      and the anastomosis was performed under some degree of tension in 10 patients
      (62%). In group II, there was a direct injury of the internal sphincter by a
      posterior tear during the mucosal stripping in one case. Mucosectomy was easy to
      perform in 8 patients (67%) and 10 anastomoses (84%) were performed under
      tension. In both groups, there were no postoperative complications related to the
      mucosectomy or to the anastomosis itself. Functional results were good, with a
      normal continence in 80% of ulcerative colitis patients and 92% of familial
      adenomatous polyposis patients. Review of histological sections of the stripped
      anal mucosa in group I showed chronic active ulcerative colitis in 8 patients
      (50%), chronic non-active ulcerative colitis in 4 (25%) and quiescent ulcerative
      colitis in 4 (25%). There was only one case of moderate dysplasia in a patient
      with a Dukes A carcinoma. In group II, anal mucosa showed micropolyps in all
      cases with mild dysplasia in 3 cases (25%) and moderate dysplasia in 9
      (75%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7813865
TI  - [Study of receptors of the digestive smooth muscle: value of isolated smooth
      muscle cells].

PMID- 7813866
TI  - [Occurrence of hepatic hemangiomas in pregnancy].
AB  - We report on the case of a 29-year-old woman, who had been on oral contraceptive
      steroids for 10 years, in whom four liver haemangiomas were found. At least two
      of them, and probably a third, have occurred during her second pregnancy. To our
      knowledge, this is the first report suggesting the occurrence of liver
      haemangioma during pregnancy. This case suggests that sexual hormones, especially
      estrogens, could play a role in the development or the occurrence of hepatic
      haemangioma.

PMID- 7813867
TI  - [Acute hepatitis caused by Listeria monocytogenes infection].
AB  - We report the case of a 40 year-old woman, pregnant for 4 months, with acute
      hepatitis revealed by jaundice, fever and high serum aminotransferase levels.
      Infection by Listeria monocytogenes was demonstrated by blood cultures. The
      course of the disease was characterized by abortion and complete recovery of
      hepatitis within 4 weeks after antibiotic administration. This report shows that
      listeriosis can cause acute severe hepatitis.

PMID- 7813868
TI  - [Aneurysm of the portal vein associated with aneurysm of the splenic artery].
AB  - Portal vein aneurysm is very rare. A case of portal vein aneurysm without
      symptoms of portal hypertension is described. Ultrasonography demonstrated a
      hypoechoic mass at the isthmic region of the pancreas. Computed tomography
      demonstrated the vascular origin of the mass. Angiography showed a portal vein
      aneurysm, measuring 3 cm in diameter, at the junction of portal vein trunk and
      splenic vein. The association with a splenic artery aneurysm and absence of
      portal hypertension lead us to suggest that our case is congenital. Non-invasive
      diagnostic methods are useful to recognize the pathology of portal vein aneurysm
      and prevent complications especially those related to a possible portal
      hypertension.

PMID- 7813869
TI  - [Singular diaphragm-like colonic stricture and short-term administration of a non
      steroidal anti-inflammatory drug].
AB  - A case of diaphragm-like stricture of the colon induced by non steroidal anti
      inflammatory drug (diclofenac LP) is reported in a 65-year-old man who presented
      abdominal pain. Colonoscopy revealed ulcer in the transverse right colon. The
      patient gradually developed diaphragm-like stricture in the transverse right
      colon. A right hemicolectomy was performed.

PMID- 7813870
TI  - [Cholangitis induced by an obstructive blood clot after endoscopic
      sphincterotomy].

PMID- 7813871
TI  - [Portal cavernoma compressing the common bile duct, diagnosed by color Doppler
      and porto CT scan].

PMID- 7813872
TI  - [Calculi of the common bile duct around a surgical metallic clip: "cat's eye
      calculi"].

PMID- 7813873
TI  - [Intrathoracic volvulus of the stomach after celioscopic surgery for
      gastroesophageal reflux, using Rampal's technique].

PMID- 7813874
TI  - [Urticaria caused by omeprazole].

PMID- 7813875
TI  - [Symptomatic annular pancreas in an adult].

PMID- 7813876
TI  - [Ulcerative hemorrhagic proctitis caused by Klebsiella oxytoca after treatment
      with an amoxicillin-clavulanic acid combination].

PMID- 7813877
TI  - [Allergic reaction during preparation for colonoscopy].

PMID- 7813878
TI  - [Urticaria after ingestion of polyethylene glycol].

PMID- 7813879
TI  - [Endoscopic sclerotherapy: does propranolol reduce the risk of hemorrhagic
      recurrence?].

PMID- 7813880
TI  - [Hepatorenal syndrome: incidence, predictive factors and prognosis].

PMID- 7813881
TI  - The Dictyostelium cell cycle and its relationship to differentiation.
AB  - The dictyostelium vegetative cell cycle is characterized by a short mitotic
      period followed immediately by a short S-phase (less than 30 min) and a long and
      variable G2 phase. The cell cycle continues during differentiation despite a
      decrease in cell mass: DNA replication and mitosis occur early in development and
      also at the tipped aggregate stage. Cells that are in mitosis, S-phase or early
      G2, when starved differentiate into prestalk cells and cells that are in the
      middle of G2 differentiate into prespore cells. We postulate that there is a
      restriction point late in the G2 phase, about 1-2 h before mitosis, where the
      cells can be arrested either by starvation and the initiation of development, by
      growing into stationary phase, or by prolonged incubation at low temperature.
      During development, this block persists to the tipped aggregate stage, where it
      is specifically released in prespore cells, and these cells then go through one
      more round of cell division. Genes encoding components of the cell cycle
      machinery have recently been isolated and attempts to specifically block the cell
      cycle by reverse genetics to study the effects on differentiation have been
      initiated.

PMID- 7813882
TI  - Pulsed-field gel electrophoresis of the genomic restriction fragments of
      coagulase-negative staphylococci.
AB  - The genomes of 47 coagulase-negative staphylococcal strains assigned to different
      species were analysed by pulsed-field electrophoresis. The strains were clustered
      on the basis of their similarity in the SmaI restriction patterns into various
      groups, each group consisting of the type strain and the strains whose SmaI
      restriction patterns were similar to that of the type of strain. The SmaI
      restriction groups seem to correspond to the following species: Staphylococcus
      warneri, S. hominis, S. xylosus, S. lugdunensis, S. kloosii, S. haemolyticus, S.
      lentus, S. cohnii, S. equorum, S. chromogenes, S. saprophyticus, S. simulans, S.
      carnosus, S. capitis and S. auricularis. The species S. sciuri, S. caseolyticus,
      S. gallinarum, S. epidermidis and S. schleiferi were represented only by their
      type strains and showed no similarity in their SmaI restriction patterns neither
      to each other nor to all the other species investigated here. Thus, the
      classification of coagulase-negative staphylococcal strains into the above
      species seems to be confirmed also by genome restriction analysis carried out by
      pulsed-field gel electrophoresis.

PMID- 7813883
TI  - Molecular characterization of the Pseudomonas putida 2,3-butanediol catabolic
      pathway.
AB  - The 2,3-butanediol dehydrogenase and the acetoin-cleaving system were
      simultaneously induced in Pseudomonas putida PpG2 during growth on 2,3-butanediol
      and on acetoin. Hybridization with a DNA probe covering the genes for the E1
      subunits of the Alcaligenes eutrophus acetoin cleaving system and nucleotide
      sequence analysis identified acoA (975 bp), acoB (1020 bp), apoC (1110 bp), acoX
      (1053 bp) and adh (1086 bp) in a 6.3-kb genomic region. The amino acid sequences
      deduced from acoA, acoB, and acoC for E1 alpha (M(r) 34639), E1 beta (M(r)
      37268), and E2 (M(r) 39613) of the P. putida acetoin cleaving system exhibited
      striking similarities to those of the corresponding components of the A.
      eutrophus acetoin cleaving system and of the acetoin dehydrogenase enzyme system
      of Pelobacter carbinolicus and other bacteria. Strong sequence similarities of
      the adh translational product (2,3-butanediol dehydrogenase, M(r) 38361) were
      obtained to various alcohol dehydrogenases belonging to the zinc- and NAD(P)
      dependent long-chain (group I) alcohol dehydrogenases. Expression of the P.
      putida ADH in Escherichia coli was demonstrated. The aco genes and adh constitute
      presumably one single operon which encodes all enzymes required for the
      conversion of 2,3-butanediol to central metabolites.

PMID- 7813884
TI  - Acetivibrio cellulolyticus and Bacteroides cellulosolvens are members of the
      greater clostridial assemblage.
AB  - The nucleotide sequences of the 16S rRNA genes of Acetivibrio cellulolyticus, A.
      cellulosolvens, and Bacteroides cellulosolvens were determined and shown to be
      affiliated with the low G + C members of Gram-positive bacteria. The sequences
      for A. celluolyticus and A. cellulosolvens were revealed to be identical,
      supporting the proposal by W.D. Murray [Int. J. Syst. Bacteriol. (1986) 36, 314
      316] that A. cellulosolvens be correctly classified as A. cellulolyticus. The
      closest relative to A. cellulolyticus is Clostridium aldrichii, related at 98.5%
      sequence similarity. B. cellulosolvens and A. cellulolyticus are related at 94.4%
      sequence similarity.

PMID- 7813885
TI  - Isolation of a Francisella tularensis mutant that is sensitive to serum and
      oxidative killing and is avirulent in mice: correlation with the loss of MinD
      homologue expression.
AB  - We constructed mutant strains of Francisella tularensis biotype novicida by
      insertional mutagenesis with a kanamycin resistance (KmR) cassette. One mutant,
      KEM7, was defective for survival in macrophages in comparison with the wild-type
      (WT) strain and a random insertion strain, KEM21. While all three strains
      exhibited intracellular growth, the number of viable KEM7 present after 24-48 h
      of infection was approximately 10 times less than that of WT or KEM21. This
      observation was apparently due to a reduced number of viable KEM7 associated with
      the macrophages one hour after phagocytosis. KEM7 was approximately 3 times more
      susceptible than WT or KEM21 to killing by the products of the xanthine-xanthine
      oxidase reaction or by hydrogen peroxide. KEM7 was also found to be susceptible
      to killing by serum, whereas WT and KEM21 were resistant. Upon intravenous
      inoculation of C57BL/6 mice, the number of KEM7 in the livers and spleens 48 h
      post-infection was found to be 1,000- to 10,000-times less than that of either
      KEM21 or WT. DNA sequence analysis at the KmR insertion site suggested that the
      F. tularensis homologue of minD had been interrupted. Western immunoblot analysis
      confirmed the presence of a MinD homologue in F. tularensis WT and KEM21, and
      demonstrated its absence in KEM7.

PMID- 7813886
TI  - The protein encoded by the Shewanella colwelliana melA gene is a p
      hydroxyphenylpyruvate dioxygenase.
AB  - The identity of the product of the melA gene from Shewanella colwelliana with the
      enzyme p-hydroxyphenylpyruvic dioxygenase is shown. Cloning of the melA gene
      endowed Escherichia coli with the capacity to synthesize melanin-like pigments
      from L-tyrosine. E. coli contained transaminases that transforms L-tyrosine into
      p-hydroxyphenylpyruvate. This keto acid was detected in the cultures. On the
      other hand, E. coli containing melA was able to go further in the catabolic
      pathway, releasing a great amount of homogentisic acid. This acid can
      spontaneously polymerize giving the pigment. Furthermore, p-hydroxyphenyl
      pyruvate dioxygenase activity was detected in this system. Analysis of the
      deduced amino acid sequence revealed a high homology with the p
      hydroxyphenylpyruvate dioxygenase enzyme from different organisms.

PMID- 7813887
TI  - The urease structural gene ureA in Rhizobium meliloti is preceded by an open
      reading frame necessary for urease activity.
AB  - An open reading frame (ORF1) located upstream of the urease structural gene ureA
      in Rhizobium meliloti strain AK631 was cloned and characterized by DNA
      sequencing. Comparison of the amino acid sequence revealed partial homology with
      the urease accessory gene ureD of Klebsiella aerogenes and Proteus mirabilis.
      Mutational analysis of ORF1 showed that the gene is necessary for urease
      activity. Its function is still unknown.

PMID- 7813888
TI  - Analysis of the cysteine proteinases of Leishmania mexicana and Trypanosoma cruzi
      using specific antisera.
AB  - Antisera raised against papain and cysteine proteinases (CPs) purified from
      Leishmania mexicana and Trypanosoma cruzi have been used to study the proteins in
      the two parasites. The antisera against the major CP of T. cruzi (cruzipain) not
      only cross-reacted with known CPs of L. mexicana but also detected stage-specific
      molecules that may represent previously unrecognised CPs. The binding of the same
      antisera to extracts of different life cycle stages of T. cruzi suggested that
      the stages possess different isoforms of cruzipain. The lack of cross-reactivity
      of anti-papain antiserum against cruzipain suggests that the major immunogenic
      epitopes of these CPs are different, whereas the detection of the major CPs of L.
      mexicana with both heterologous antisera shows that the parasite's enzymes share
      epitopes with the other CPs.

PMID- 7813889
TI  - Physical characterisation of the Escherichia coli B gene encoding nitroreductase
      and its over-expression in Escherichia coli K12.
AB  - The Escherichia coli B gene (nfnB) encoding nitroreductase has been cloned in
      Escherichia coli K-12 and its nucleotide sequence determined. The translated
      amino acid sequence was found to share substantial identity (88.5%) with the
      equivalent proteins of Enterobacter cloacae and Salmonella typhimurium. When the
      structural gene was placed under the transcriptional control of either the trp or
      lac promoter, recombinant nitroreductase was accumulated to 33% and 25% of the
      cell's soluble protein, respectively. Substitution of the nfrB ribosome binding
      site with that of the E. coli lacZ gene reduced production levels of
      nitroreductase. The sequenced region also contained two incomplete open reading
      frames of unknown function.

PMID- 7813890
TI  - Mutation in dipZ leads to reduced production of active human placental alkaline
      phosphatase in Escherichia coli.
AB  - We have tested the expression of alkaline phosphatases in a mutant strain of
      Escherichia coli deficient in dipZ, a gene coding for a protein involved in
      cytochrome c biogenesis, and the isogenic wild-type strain. The yield of soluble
      and active human placental alkaline phosphatase was significantly reduced in the
      mutant but could be fully recovered by expression of dipZ subcloned in a vector
      with low copy number. Overexpression of E. coli alkaline phosphatase was
      unaffected in the mutant with or without dipZ co-expression.

PMID- 7813891
TI  - Heat shock inhibits and activates different protein degradation pathways and
      proteinase activities in Neurospora crassa.
AB  - In Neurospora crassa, heat shock treatment inhibits proteolytic activity. ATP
      independent proteinases were analysed after polyacrylamide gel electrophoresis
      using renaturing gelatine gels. Proteinases of 24, 29, and 130 kDa were shown to
      be inhibited by heat shock and were further characterized as to their properties.
      A major part of the heat shock-induced inhibition is probably due to suppression
      of de novo synthesis of proteinases as deduced from experiments with
      cycloheximide. During several hours of recovery from heat shock, the inhibition
      of overall protein degradation and ATP-independent proteinases is reversed.
      Azocasein assays as well as pulse-chase experiments further showed that ATP
      dependent protein degradation is only slightly affected by heat shock. Two ATP
      binding proteinases of about 60 and 160 kDa even show an increased activity after
      heat shock. The degradation rate of heat shock proteins is inhibited by heat
      shock treatment, indicating that they are degraded by ATP-independent
      proteinases. Western blot analysis of a approximately 40-kDa degradation product
      of HSP70 containing its amino terminal portion revealed a reduction in the amount
      of this peptide after heat shock.

PMID- 7813892
TI  - Cloning and expression in Escherichia coli of the gene encoding a novel L-2,4
      diaminobutyrate decarboxylase of Acinetobacter baumannii.
AB  - The gene encoding L-2,4-diaminobutyrate decarboxylase (DABA DC) was cloned from
      Acinetobacter baumannii ATCC 19606. The gene was evidently under the control of
      its own promoter. Interestingly, the host carrying this clone also produced an
      appreciable amount of 1,3-diaminopropane. Restriction mapping and subsequent
      subcloning of the cloned insert localized the DABA DC gene within a 2.45-kb
      SphI/EcoRI fragment. For endogenous production of DAP, a 1.75-kb EcoRI/PstI
      region downstream from the DABA DC gene was further required. Southern blot
      hybridization revealed some heterogeneity in the DABA DC genes among other
      Acinetobacter species.

PMID- 7813893
TI  - Association of the CAMP phenomenon in Actinobacillus pleuropneumoniae with the
      RTX toxins ApxI, ApxII and ApxIII.
AB  - A non-hemolytic mutant of Actinobacillus pleuropneumoniae serotype 5 has a
      deletion spanning the entire apxI operon. Therefore it does not produce ApxI and
      is unable to secrete ApxII. This mutant also has lost the co-hemolytic CAMP
      effect which is characteristic of the species A. pleuropneumoniae. The CAMP
      effect is restored when the mutant is complemented in trans by the apxIBD genes
      cloned in a broad host range vector, thus permitting secretion of ApxII, or when
      the entire apxI operon is cloned in the mutant, thus restoring the original toxin
      phenotype ApxI+ ApxII+. When the toxins ApxI, ApxII or ApxIII individually are
      expressed and secreted from E. coli harboring recombinant plasmids containing the
      genes apxICA and apxIBD or apxIICA and apxIBD or apxIIICABD, respectively, the
      distinct CAMP phenomenon is produced by the recombinant strains. The CAMP
      phenomenon is strongest by the recombinant E. coli strain expressing the non
      hemolytic ApxIII, somewhat less when ApxI is expressed, and weak when ApxII is
      expressed. In A. pleuropneumoniae the CAMP phenomenon is also strongest in those
      serotypes which express ApxIII. The CAMP phenomenon of A. pleuropneumoniae is
      assumed to be directly caused by any of the RTX-toxins ApxI, ApxII or ApxIII. A
      previously reported gene from A. pleuropneumoniae, named cfp or hlyX, which
      provides E. coli strains with a hemolytic character and a CAMP phenomenon, shows
      high similarity to the E. coli global regulation gene fnr, and which is able to
      complement a delta fnr mutant.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7813894
TI  - Extended latent class approach to the study of familial/sporadic forms of a
      disease: its application to the study of the heterogeneity of schizophrenia.
AB  - When no method exists for detecting genetic forms of a disorder, epidemiologists
      classify probands according to the presence or absence of an affected relative
      (familial or sporadic). Not only is this a surrogate measure but if the risk for
      the disorder is associated with characteristics such as age and gender, then
      probands with varied distributions of these characteristics among their relatives
      are subject to misclassification. A latent class approach is presented which
      explicitly models the relationship between the affected status of the relatives
      and the unobservable familial/sporadic status of the proband in order to adjust
      for these characteristics. Lastly, an approach is introduced to correct for
      attenuation in measures of association between familial/sporadic status and other
      variables that could result if probands are misclassified. This approach
      incorporates the latent class probabilities directly into the regression model
      without classifying probands. These methods are applied to a study of the
      heterogeneity of schizophrenia.

PMID- 7813895
TI  - Lods, wrods, and mods: the interpretation of lod scores calculated under
      different models.
AB  - In this paper we examine the relationships among classical lod scores, "wrod"
      scores (lod scores calculated under the wrong genetic model), and "mod" scores
      (lod scores maximized over genetic model parameters). We compare the behavior of
      these scores when the state of nature is linkage to their behavior when the state
      of nature is no linkage. We describe sufficient conditions for mod scores to be
      valid and discuss their use to determine the correct genetic model. We show that
      lod scores represent a likelihood-ratio test for independence. We explain the
      "ascertainment-assumption-free" aspect of using mod scores to determine mode of
      inheritance and we set this aspect into a well-established statistical framework.
      Finally, we summarize practical guidelines for the use of mod scores.

PMID- 7813896
TI  - The contribution of maternal epilepsy and its treatment to the etiology of oral
      clefts: a population based case-control study.
AB  - The associations between maternal epilepsy and anticonvulsant drug therapy with
      the risk of oral clefts in the offspring were investigated using data from a
      population-based case-control study. Cases included 238 infants with cleft lip +/
      cleft palate (CLP) and 107 infants with cleft palate (CP) ascertained through
      the Metropolitan Atlanta Congenital Defects Program (MACDP) between 1968 and
      1980. Controls included 3029 population-based normal infants. Histories of
      maternal epilepsy and drug therapy during pregnancy were compared between cases
      and controls using maternal interviews and reviews of hospital medical records.
      Maternal epilepsy was associated with increased risk of nonsyndromic CLP (OR =
      3.78, 95% C.I. 1.65-7.88), and less with CP (OR = 1.75, 95% C.I. 0.20-6.99).
      Therapy during pregnancy was associated with the greatest excess risk (CLP OR =
      7.77, C.I. 2.02-26.0; CP OR = 3.61, C.I. 0.08-26.5). The use of polytherapy was
      associated with the highest risk (CLP OR = 10.5, C.I. 1.52-59.9). Adjustment for
      potential confounding variables in the study did not change these findings. In
      this well-defined population, maternal epilepsy and its treatment account for a
      small proportion of nonsyndromic oral clefts (attributable fraction CLP = 3.3%,
      CP = 0.9%).

PMID- 7813897
TI  - Affected sib pair identity by state analyses.
AB  - Four methods using identity by state (IBS) data from affected sib pairs are
      compared for their ability to detect linkage between a diallelic marker and
      disease. A joint null hypothesis of no linkage and no linkage disequilibrium
      between the marker and disease must be considered. Two tests have undesirable
      properties in the case of linkage disequilibrium. Which of the other two tests
      has more power is dependent on the presence or not of linkage disequilibrium. The
      procedure of choice when possible is to type parents of affected sib pairs: the
      null hypothesis of no linkage can then be tested using identity by descent (IBD)
      values from informative parents, and the null hypothesis of no marker association
      with disease (linkage equilibrium) can be tested independently using the marker
      allele frequencies in the affected sib pairs.

PMID- 7813898
TI  - Familial risks for Alzheimer disease from a population-based series.
AB  - Kaplan-Meier risks estimates are calculated and compared for two consecutive
      series (N1 = 840, N2 = 819) of first-degree relatives of Alzheimer disease (AD)
      patients diagnosed as either "probable" or "autopsy-confirmed" AD. The
      consistency of results increases confidence in estimates and suggests consistent
      case ascertainment over 8 years. Lifetime risk estimates to age 88 for the
      combined sample (23.4% +/- 3.0%) do not approach the 50% risk compatible with an
      autosomal dominant model of transmission. These results support our previous
      finding and suggest that an autosomal dominant gene(s) is not responsible for all
      cases of AD.

PMID- 7813899
TI  - Genetic influences on age-related change in total cholesterol, low density
      lipoprotein-cholesterol, and triglyceride levels: longitudinal apolipoprotein E
      genotype effects.
AB  - This study addressed the possible influence of apolipoprotein E (apo E) genotype
      on age-related changes in total cholesterol (TC), low density lipoprotein
      cholesterol (LDL-C), and triglyceride (TG) levels in older males. Apo E is a
      component of LDL, is a ligand for the LDL receptor, and apo E genotype has been
      consistently associated with variation in mean levels of TC and LDL-C, and also
      appears to influence TG levels. Using male twins followed longitudinally between
      mean ages of 48 and 63 years, the change in TC, LDL-C, and TG over time for
      individuals with the epsilon 3 epsilon 3 and the epsilon 3 epsilon 4 genotypes
      was contrasted. At exam 1 mean TC and LDL-C levels were lower in the epsilon 3
      epsilon 3 group than in the epsilon 3 epsilon 4 group, but at exam 3 mean TC and
      LDL-C levels were significantly higher in the epsilon 3 epsilon 3 group than in
      the epsilon 3 epsilon 4 group. The rate of change in TC and LDL-C with age
      differed significantly between epsilon 3 epsilon 3 and epsilon 3 epsilon 4
      groups. Results for TG were not statistically significantly. These findings
      suggest that the apo E genotype effects on risk of coronary artery disease may be
      age-dependent. This study demonstrates the value of longitudinal studies in
      refining models for genetic risk factors for disease.

PMID- 7813900
TI  - Coding of pointers in the segregation analysis program POINTER.

PMID- 7813901
TI  - The HSR on chromosome 1 of the house mouse, Mus domesticus: distribution and
      frequency in Switzerland.
AB  - A total of 357 house mice (Mus domesticus) from 83 localities uniformly
      distributed throughout Switzerland were screened for the presence of a
      homogenously staining region (HSR) on chromosome 1. Altogether 47 mice from 11
      localities were HSR/+ or HSR/HSR. One sample of 11 individuals all had an HSR/HSR
      karyotype. Almost all mice with the variant were collected from the Rhone valley
      (HSR frequency: 61%) and Val Bregaglia (HSR frequency: 81%). For samples from
      most of the area of Switzerland, the HSR was absent. There was no strong
      association between the geographic distribution of the HSR and the areas of
      occurrence of metacentrics. However, at Chiggiogna the HSR was found on Rb (1.3).
      Possible explanations for the HSR polymorphism are discussed.

PMID- 7813902
TI  - Selection on reaction norms, genetic correlations and constraints.
AB  - Two approaches to the evolution of phenotypic plasticity in heterogeneous
      environments have recently been put forward. The first focuses on selection on
      the character expression within each environment; plasticity is seen as a by
      product of local selection in various habitats. The second approach focuses on
      selection on the parameters of the response function of genotypes, and selection
      is thought to change the frequencies of 'plasticity' genes that affect the
      function. This paper discusses the relationship between the two approaches, with
      emphasis on applications. A method is described that allows switching from one
      approach to the other. It is argued that character state and reaction norm
      approaches, while to a large extent interchangeable, usually differ in the
      response function chosen. This choice, however, may strongly affect the
      biological interpretation. The methods outlined in this paper permit one to look
      at the data from different perspectives in order to avoid this danger.

PMID- 7813903
TI  - Simulation of marker assisted selection for non-additive traits.
AB  - Marker Assisted Selection (MAS) based on additive effects associated with alleles
      at marker loci, estimated by linear regression of individual phenotype on the
      markers, was applied to characters with non-additive gene action and non-additive
      environment. The base population was the F2 generation of a cross between two
      inbred lines. Computer simulations of MAS were conducted for characters with
      dominance, epistasis and genotype-environment interaction approximated by the
      'additive-multiplicative' model. MAS was more effective than purely phenotypic
      selection in all cases. The efficiency of MAS for characters with non-additive
      gene action is comparable to (and for negative dominance even higher than) the
      efficiency of MAS for strictly additive characters. Environmental non-additivity,
      however, lowers the efficiency of MAS. Almost all results concerning the
      efficiency of MAS in our previous simulations of purely additive traits are
      applicable to non-additive traits.

PMID- 7813904
TI  - Decay of linkage disequilibrium in a finite island model.
AB  - Time-dependent behaviour of linkage disequilibrium when there was initial linkage
      disequilibrium is studied in a finite island model assuming neutrality. Explicit
      expressions for linkage disequilibrium parameters are obtained. From these
      expressions, the initial and the ultimate decay rates of linkage disequilibrium
      parameters are found to be increased and decreased, respectively, by finiteness
      of the population when recombination rate, migration rate and inverse of
      subpopulation size are of comparable order. Thus, linkage disequilibrium created
      in the past may persist longer in smaller subdivided populations. Also,
      differentiation of the gametic parameter of linkage disequilibrium among
      subpopulations is found to diminish quickly compared to the linkage
      disequilibrium in the whole population. Implications of these results for the
      interpretation of linkage disequilibria in natural populations are discussed.

PMID- 7813905
TI  - The Hermes transposable element from the house fly, Musca domestica, is a short
      inverted repeat-type element of the hobo, Ac, and Tam3 (hAT) element family.
AB  - The genome of the house fly, Musca domestica, contains an active transposable
      element system, called Hermes. Using PCR and inverse PCR we amplified and
      sequenced overlapping segments of several Hermes elements and from these data we
      have constructed a 2749 bp consensus Hermes DNA sequence. Hermes termini are
      composed of 17 bp imperfect inverted repeats that are almost identical to the
      inverted terminal repeats of the hobo element of Drosophila melanogaster. Full
      length Hermes elements contain a single long ORF capable of encoding a protein of
      612 amino acids which is 55% identical to the amino acid sequence of the hobo
      transposase. Comparison of the ends of the Hermes and hobo elements to those of
      the Ac element of Zea mays, and the Tam3 element of Antirrhinum majus, as well as
      several other plant and insect elements, revealed a conserved terminal sequence
      motif. Thus Hermes is clearly a member of the hobo, Ac and Tam3 (hAT)
      transposable element family, other members of which include the Tag1 element from
      Arabidopsis thaliana and the Bg element from Zea mays. The evolution of this
      class of transposable elements and the potential utility of Hermes as a genetic
      tool in M. domestica and related species are discussed.

PMID- 7813906
TI  - At least four genes and sex are associated with susceptibility to urethane
      induced pulmonary adenomas in mice.
AB  - Susceptibility to urethane-induced lung adenomas in mice has a polygenic mode of
      inheritance, with no obvious discontinuity in lung tumour counts among 37 AXB
      recombinant inbred strains. However, mean tumour counts were markedly higher in
      strains carrying the A/J allele at the Kras2 and H2 complex than in those
      carrying the C57BL/ allele. In 162 F2 hybrids and small numbers of both
      backcrosses between strain A/J (susceptible) and C57/BL/6 (resistant) mice, five
      factors influencing susceptibility were identified. Variation due to the 'major'
      Kras2 locus (chromosome 6) accounted for 60% of the total variation. 'Minor' loci
      linked to microsatellite markers Tnfb (in the H2 complex), D9Mit11 and D19Mit16
      (on chromosomes 17, 9 and 19, respectively) accounted for a further 13% of the
      variation, and males had more tumours than females with sex differences
      accounting for 2% of the variation. No significant association with 32 other loci
      was detected. On a square-root transformed scale, heterozygotes at all marker
      loci were of intermediate susceptibility compared with homozygotes. The three
      minor loci and sex only affected lung tumour counts when at least one susceptible
      Kras2 allele was present.

PMID- 7813907
TI  - I factors in Drosophila melanogaster: transposition under control.
AB  - I factors are responsible for the I-R system of hybrid dysgenesis in Drosophila
      melanogaster. They belong to the LINE class of mobile elements, which transpose
      via reverse transcription of a full-length RNA intermediate. I factors are active
      members of the I element family, which also contains defective I elements that
      are immobilized within peri-centromeric heterochromatin and represent very old
      components of the genome. Active I factors have recently invaded natural
      populations of Drosophila melanogaster, giving rise to inducer strains. Reactive
      strains, devoid of active I factors, derive from old laboratory stocks
      established before the invasion. Transposition of I factors is activated at very
      high frequencies in the germline of hybrid females issued from crosses between
      females from reactive strains and males from inducer strains. It results in the
      production of high rates of mutations and chromosomal rearrangements as well as
      in a particular syndrome of sterility. The frequency of transposition of I
      factors is dependent on the amount of full-length RNA that is synthesized from an
      internal promoter. This full-length RNA serves both as an intermediate of
      transposition and presumably as a messenger for protein synthesis. Regulators of
      transposition apparently affect transcription initiation from the internal
      promoter. The data presented here lead to the proposal of a tentative model for
      transposition.

PMID- 7813908
TI  - The Doc transposable element in Drosophila melanogaster and Drosophila simulans:
      genomic distribution and transcription.
AB  - The mobile element Doc is similar in structure and coding potential to the LINE
      families found in various organisms. In this paper, we analyze the insertional
      and structural polymorphism of this element and show that it appears to have a
      long evolutionary history in the genome of D. melanogaster. Like the family of I
      elements, the Doc family seems to display three types of elements: full length
      elements, defective members that have recently transposed and long since
      immobilized members common to each D. melanogaster strain. These three classes of
      Doc elements seem to be present in D. simulans, a closely related species to D.
      melanogaster. Furthermore, we show that Doc is transcribed as a polyadenylated
      RNA of about 5 kb in length, presumed to be a full length RNA. This transcript is
      present in different tissues and at different stages of Drosophila development.
      These results are compared with previous records on the chromosomal distribution
      of LINEs or other transposable element families. Doc transcription is analyzed in
      an attempt to understand the link between Doc transcription and transposition.

PMID- 7813910
TI  - IS231 and other Bacillus thuringiensis transposable elements: a review.
AB  - Bacillus thuringiensis is an entomopathogenic bacterium whose toxicity is due to
      the presence in the sporangia of delta-endotoxin crystals active against
      agricultural pests and vectors of human and animal diseases. Most of the genes
      coding for these toxin proteins are plasmid-borne and are generally structurally
      associated with insertion sequences (IS231, IS232, IS240, ISBT1 and ISBT2) and
      transposons (Tn4430 and Tn5401). Several of these mobile elements have been shown
      to be active and are believed to participate in the crystal gene mobility,
      thereby contributing to the variation of bacterial toxicity. Structural analysis
      of the iso-IS231 elements indicates that they are related to IS1151 from
      Clostridium perfringens and distantly related to IS4 and IS186 from Escherichia
      coli. Like the other IS4 family members, they contain a conserved transposase
      integrase motif found in other IS families and retroviruses. Moreover, functional
      data gathered from IS231A in Escherichia coli indicate a non-replicative mode of
      transposition, with a marked preference for specific targets. Similar results
      were also obtained in Bacillus subtilis and B. thuringiensis, and a working model
      for DNA-protein interactions at the target site is proposed.

PMID- 7813909
TI  - Structural features of mag, a gypsy-like retrotransposon of Bombyx mori, with
      unusual short terminal repeats.
AB  - Mag is a retrotransposon found as an insert in the Sericin 2 gene. It is present
      in a few copies--4 to 15--dispersed in the genome of different strains of Bombyx
      mori as well as in Bombyx mandarina. Flanked by a 5 bp target sequence with no
      sequence specificity, it is bordered by direct repeats of 77 nucleotides. Despite
      their unusual short size, these terminal repeats and their immediately adjacent
      sequences present all the signals necessary for transcription into genomic RNA
      and for reverse transcription. Mag contains two overlapping open reading frames
      which are organized as the gag and pol genes of retroviruses and encode putative
      nucleic acid binding peptide, protease, reverse transcriptase, RNase H and
      endonuclease in this order. Sequence comparison of these proteins places mag
      within the gypsy group of LTR retrotransposons next to the echinoderm element
      SURL.

PMID- 7813911
TI  - Mosquito transposable elements.
AB  - Most of the transposons so far characterized from mosquito genomes are
      retroelements which seem to be distributed worldwide. The Juan transposons
      constitute a family of non-LTR retroelements, or LINE-retroposons, which are
      dispersed in the genomes of several mosquito species. Three different Juan
      subfamilies have been characterized, each being amplified in the genomes of many
      strains, if not all, of a given mosquito species. These subfamilies have been
      designated respectively Juan-C in Culex pipiens, Juan-Ct in Culex tarsalis and
      Juan-A in Aedes aegypti. A large number of the Juan retroposons which are
      amplified in the mosquito genomes are apparently full-length copies and
      potentially encode the enzymes necessary for their transposition, a nucleic acid
      binding protein and a reverse transcriptase. However, these complete Juan copies
      seem to be most frequently transcriptionally silent in insects reared under
      laboratory conditions. A few of them are transcribed in C. pipiens cells grown in
      vitro, but from an external promoter, the Juan-C specific RNA being fused to an
      upstream RNA sequence. Therefore, the transcription of Juan retroposons seems to
      depend on external promoters which are most frequently inactive. The occurrence
      and distribution of Juan retroposon subfamilies among mosquito species do not
      reflect the phylogeny of these species. Furthermore, complete Juan-C and Juan-A
      copies which are reiterated in strains collected from regions covering different
      continents are nearly identical. Juan-C copies belonging to geographically
      different C. pipiens strains display low levels of divergence between their
      nucleotide sequences and many of the mutations which have occurred among these
      copies do not alter their coding potential. These results indicate that the Juan
      retroposons occur as homogeneous subfamilies distributed worldwide and that
      selective constraints against amino acid change have been acting recently on
      these elements, despite the fact that they are now highly repeated through
      mosquito genomes. Therefore, Juan transposons have most probably been recently
      amplified in mosquito genomes. Each subfamily may have been amplified from one
      master element present in a unique population which has since spread worldwide.
      Alternatively, this amplification may have arisen in many mosquito populations,
      but from highly conserved master elements submitted to selection pressures.
      Horizontal transfers between species may also have contributed to the spread of
      these transposons.

PMID- 7813913
TI  - Horizontal transmission versus ancient origin: mariner in the witness box.
AB  - The transposable element mariner has been found in many species of Drosophilidae,
      several groups of Arthropods, and more recently in Platyhelminthes as well as in
      a phytopathogenic fungus. In the family Drosophilidae, the distribution of
      mariner among species shows many gaps, and its geographical distribution among
      endemic species is restricted to Asia and Africa. Among mariner elements in
      species within and outside the Drosophilidae, the similarities in nucleotide
      sequence and the amino acid sequence of the putative transposase reveal many
      phylogenetic inconsistencies compared with the conventional phylogeny of the host
      species. This paper discusses the contrasting hypotheses of horizontal transfer
      versus ancestral origin proposed to explain these results.

PMID- 7813914
TI  - Functional analysis of the tobacco Tnt1 retrotransposon.
AB  - Retroelements represent by far the largest and most widespread class of mobile
      genetic elements. Representative of several classes of retrotransposons have been
      characterized in a broad range of plant species, but only a few of them have been
      shown to be active. Among these, the tobacco Tnt1 retrotransposon has been
      isolated after insertion mutagenesis and is one of the very few to be
      transcriptionally active. Tnt1 expression is strongly regulated in a tissue
      specific and developmental manner. Moreover, Tnt1 expression is induced by a
      range of biotic or abiotic elicitors, which all have in common the ability to
      induce the plant defense response. Regulatory sequences involved in this elicitor
      mediated induction have been located in the LTR U3 region. The link between Tnt1
      activation and the plant defense response might represent an example of the
      involvement of transposable elements in genome restructurations needed in
      response to environmental fluctuations such as pathogen attacks.

PMID- 7813912
TI  - Genome and stresses: reactions against aggressions, behavior of transposable
      elements.
AB  - The action of stresses on the genome can be considered as responses of cells or
      organisms to external aggressions. Stress factors are of environmental origin
      (climatic or trophic) or of genomic nature (introduction of foreign genetic
      material, for example). In both cases, important perturbations can occur and
      modify hereditary potentialities, creating new combinations compatible with
      survival; such a situation may increase the variability of the genome, and allow
      evolutive processes to take place. The behavior of transposable elements under
      stress conditions is thus of particular interest, since these sequences are
      sources of mutations and therefore of genetic variability; they may play an
      important role in population adaptation. The survey of the available experimental
      results suggest that, although some examples of mutations and transposable
      elements movements induced by external factors are clearly described,
      environmental injuries or introduction of foreign material into a genome are not
      systematically followed by drastic genomic changes.

PMID- 7813915
TI  - The human episome HALF1: structure of its genomic counterpart.
AB  - A human episomal sequence (HALF1) has been identified by its ability to restore
      expression of hepatic functions when used to transfect a rat dedifferentiated
      cell line. The genomic equivalent of this human episome (gHALF1) and its flanking
      sequences were analyzed. HALF1 itself does not present the characteristics of a
      transposable element but half of its sequence corresponds to retroposons,
      including Alu and L1 repeats and a processed pseudogene, known to transpose via
      RNA intermediates. The structural characteristics of these different kinds of
      retroposons and their origin and evolution were analyzed.

PMID- 7813916
TI  - Regulation of bacteriophage Mu transposition.
AB  - Bacteriophage Mu is a transposon and a temperate phage which has become a
      paradigm for the study of the molecular mechanism of transposition. As a
      prophage, Mu has also been used to study some aspects of the influence of the
      host cell growth phase on the regulation of transposition. Through the years
      several host proteins have been identified which play a key role in the
      replication of the Mu genome by successive rounds of replicative transposition as
      well as in the maintenance of the repressed prophage state. In this review we
      have attempted to summarize all these findings with the purpose of emphasizing
      the benefit the virus and the host cell can gain from those phage-host
      interactions.

PMID- 7813917
TI  - Transposable elements and adaptation of host bacteria.
AB  - A transposable element (TE) is a mobile sequence present in the genome of an
      organism. TEs can cause lethal mutations by inserting into essential genes,
      promoting deletions or leaving short sequences upon excision. They therefore may
      be gradually eliminated from mixed populations of haploid micro-organisms such as
      Escherichia coli if they cannot balance this mutation load. Horizontal
      transmission between cells is known to occur and promote the transfer of TEs, but
      at rates often too low to compensate for the burden to their hosts. Therefore,
      alternative mechanisms should be found by these elements to earn their keep in
      the cells. Several theories have been suggested to explain their long-term
      maintenance in prokaryotic genomes, but little molecular evidence has been
      experimentally obtained. In this paper, the permanence of transposable elements
      in bacterial populations is discussed in terms of costs or benefits for the
      element and for the host. It is observed that, in all studies yet reported, the
      elements do not behave in their host as selfish DNA but as a co-operative
      component for the evolution of the couple.

PMID- 7813920
TI  - Invasion of the hobo transposable element studied by in situ hybridization on
      polytene chromosomes of Drosophila melanogaster.
AB  - The invasion kinetics of hobo transposable element in the Drosophila melanogaster
      genome was studied by in situ hybridization on the polytene chromosomes. Six
      independent lines of Drosophila melanogaster flies that had been previously
      transformed by microinjection of the pHFL1 plasmid containing a complete hobo
      element were followed over 50 generations. We observed that hobo elements were
      scattered on each of the chromosome arms, with more insertion sites on the 3R
      arm. The total number of insertion sites remains quite small, between four and
      six, at generation 52. On the 2R arm, a short inversion appeared once at
      generation 52. Most of the integration sites reported here were already described
      for several transposons but some of them appear to be hotspots for hobo elements.

PMID- 7813919
TI  - The evolutionary genetics of the hobo transposable element in the Drosophila
      melanogaster complex.
AB  - Hobo elements are a family of transposable elements found in Drosophila
      melanogaster and its three sibling species: D. simulans, D. mauritiana and D.
      sechellia. Studies in D. melanogaster have shown that hobo may be mobilized, and
      that the genetic effects of such mobilizations included the general features of
      hybrid dysgenesis: mutations, chromosomal rearrangements and gonadal dysgenis in
      F1 individuals. At the evolutionary level some hobo-hybridizing sequences have
      also been found in the other members of the melanogaster subgroup and in many
      members of the related montium subgroup. Surveys of older collected strains of D.
      melanogaster suggest that complete hobo elements were absent prior to 50 years
      ago and that they have recently been introduced into this species by horizontal
      transfer. In this paper we review our findings and those of others, in order to
      precisely describe the geographical distribution and the evolutionary history of
      hobo in the D. melanogaster complex. Studies of the DNA sequences reveal a
      different level of divergence between the group D. melanogaster, D. simulans and
      D. mauritiana and the fourth species D. sechellia. The hypothesis of multiple
      transfers in the recent past into the D. melanogaster complex from a common
      outside source is discussed.

PMID- 7813918
TI  - Drosophila P element: transposition, regulation and evolution.

PMID- 7813922
TI  - [Hypothermia in the elderly in the Negev].
AB  - Hypothermia in the elderly is a medical emergency with mortality varying from 32
      80%. Its most frequent predisposing factors, as reported in the current
      literature, are extremes of age, cold environment and alcoholism. In the Negev
      (southern region of Israel, mostly desert area) the mean temperature range during
      November-March is 9.6 to 15.2 degrees C and during April-October, 16-25.9 degrees
      C. The records of all patients with hypothermia, aged 65 and above admitted over
      a 5-year period (1984-1988) were reviewed (44 admissions of 39 patients of whom
      23 were females). 34 were admitted during the winter months and 10 during the
      rest of the year. Important associated or predisposing conditions included
      infections in 54.5%, renal failure in 29.5% and diabetes mellitus in 29.5%.
      Alcoholism (13.6%) was relatively infrequent. Those of Asian or African origin
      appeared to be at greater risk, constituting 73% of admissions, but only 47% of
      the elderly population of the Negev. The annual incidence of up to 4/1000 of
      elderly patients admitted to our medical wards, which serve a population of
      350000, indicates that hypothermia is not rare in this desert region.

PMID- 7813924
TI  - [Plasma lipid peroxidation: inhibited by drinking red wine but stimulated by
      white wine].
AB  - The effects of drinking red or white wine (11% alcohol) on the propensity of
      plasma and low density lipoprotein (LDL) to undergo lipid peroxidation (LP) was
      studied. 8 healthy men drank 400 ml of red wine a day for 2 weeks and 9 drank
      white wine similarly. The red wine supplementation resulted in a 20% similarly.
      The red wine supplementation resulted in a 20% reduction in the propensity of
      their plasma to undergo LP (in the presence of a free radical-generating system)
      and a 46% reduction in that of their LDL to undergo LP (in response to copper
      ions). Contrarily, drinking white wine for 2 weeks resulted in a 33% increase in
      propensity of plasma to undergo LP and in a 57% increase in that of LDL to
      undergo LP. The antioxidant effect of drinking red wine on plasma LP can be
      related to increase in plasma high density lipoprotein concentration, as well as
      to increase in plasma and LDL polyphenols. We conclude that some phenolic
      substance present in red, but not in white wine, may be responsible for the
      antioxidative properties of red wine supplementation for LDL LP, and thus may
      possess antiatherogenic properties.

PMID- 7813923
TI  - [Effect of polypectomy on voice quality].
AB  - Voice quality and improvement after vocal cord polypectomy was assessed in 15
      patients. The polyps were found by indirect observation; assessment of vocal
      quality was by recording isolated vowels, words and sentences said in Hebrew
      before operation and 1 and 3 months later. The recordings were analyzed using a
      computer program written at the Medical Electronics Laboratory of The Technion.
      Analysis of the 5 Hebrew vowels (a,e,i,o,u) yielded numerical and graphical data
      of formats specific for each utterance and speaker. These data were compared with
      control data taken from the literature for healthy Hebrew speakers. Statistical
      analysis (by paired t-test for matched samples) revealed a tendency to a decrease
      in difference between postoperative results and control data. Comparison of
      preoperative recordings with control data suggest that this method of voice
      condition assessment is worth considering for systematic application in clinics
      and hospitals. Among its advantages is that it permits long-term objective
      assessment of changes in voice quality. It thus supplies data for follow-up
      studies of patients and others who suffer from voice problems, especially those
      whose voice is their professional tool.

PMID- 7813921
TI  - [Neonatal alloimmune thrombocytopenia].
AB  - Neonatal alloimmune thrombocytopenia (NAIT) was first described in the 1950s. The
      disease results from maternal antiplatelet antibodies against surface antigens on
      fetal platelets due to feto-maternal platelet incompatibility. Although NAIT is
      transient, during its active phase thrombocytopenia can cause intracranial
      hemorrhage with grave neurological sequelae or death. We characterized the
      alloimmune antibodies in 29 mothers and found anti-HPA-1a (in 11 cases), anti
      HPA1b (1), anti-HPA-5a (1) and anti-HPA-5b (5). In 11 women no specific
      antibodies were identified despite characteristic disease in the newborns. 3
      neonates in the anti-HPA-1a, and 1 in the anti-HPA-1b groups were born with
      intracranial hemorrhage and are severely disabled. We described a case of
      successful prenatal treatment by a combination of steroids, high-dose
      immunoglobulins and intraumbilical platelet transfusion in a mother known to have
      anti-HPA-1, whose previous child was severely affected. It is important to
      examine antibodies in any woman whose neonate has thrombocytopenia of unknown
      etiology.

PMID- 7813925
TI  - [Medical kits in Army physicians' vehicles].
AB  - Physicians' medical kits (PMK) were distributed to 50 physicians, graduates of an
      advanced trauma life support course. The kits were always to be present in the
      physicians' designated vehicles, enabling them to provide advanced life support
      at the earliest possible stage (the "golden hour"). The kits have equipment for
      advanced airway intervention and management, chest trauma management (chest tube
      insertion, etc.) and fluid administration. To help assess the impact of the PMK
      and its cost effectiveness, questionnaires were sent to the physicians involved,
      of whom 35/50 responded. The questions included 2 subjects: the presence of the
      kit in the car and details of its use for injuries. The kit was present at all
      times in the cars of all except 1 of 31 physicians. 7 (22.5%) of them used the
      kit in 50 incidents which involved 74 injured persons. The injuries were caused
      by road accidents in 54 cases, in 17 by terrorist activity, and 3 cases involved
      heart attacks and cardiac resuscitation. Distribution of the PMK among army
      physicians appears to be valuable in the field, and before hospitalization.

PMID- 7813926
TI  - [Bacterial arthritis with E. coli in an elderly patient].
AB  - Infectious arthritis is mostly caused by hematogenous spread of Gram-positive
      bacteria, which often infects a previously damaged joint. During the past 20
      years there has been a notable increase in joint infections caused Gram-negative
      bacteria. They develop mostly in patients with systemic diseases, such as
      malignancy, cirrhosis or HIV infection, which cause an immune deficient state. We
      present an 84-year old man admitted because of fever and a diagnosis of
      pneumonia. During hospitalization he complained of pain in his right knee. On
      physical examination there was evidence of local inflammation. Infection with E.
      coli originating in the urinary tract was diagnosed, based on synovial fluid,
      blood and urine cultures. He was treated with antibiotics intravenously, the knee
      was surgically drained, and he was discharged 4 weeks after admission. There was
      no underlying systemic disease in this case that could have caused an immune
      deficient state, which could promote the Gram-negative joint infection. The case
      is presented to draw attention to the possibility of infectious arthritis in an
      elderly patient presenting with fever. In such cases the location of the
      infection may not be obvious if the infected joint is deeply located parts of
      bones such as those of the hip, shoulder, or vertebrae. In these cases the
      diagnosis may be overlooked or delayed and irreversible damage to the infected
      joint may result.

PMID- 7813927
TI  - [Sclerotherapy of postoperative lymphocele].
AB  - Postoperative lymphocele is a well-documented complication of gynecological
      operations involving pelvic and retroperitoneal lymph node dissection. It is not
      uncommon following renal transplantation. We report a 77-year-old woman with a
      lymphocele which developed 4 months after panhysterectomy. Diagnosis was by CT
      scan, confirmed by aspiration and cytology. Percutaneous drainage and
      sclerotherapy with tetracycline was curative. This appears to be the treatment of
      choice for lymphocele and is superior to repeated aspirations and surgical
      intervention, the current usual treatment.

PMID- 7813928
TI  - [Post-transfusion purpura].
AB  - Post-transfusion purpura (PTP) is a rare syndrome that may develop a week after
      blood transfusion. In this syndrome, which occurs mainly in women, blood
      transfusion is followed by severe thrombocytopenia a week later. A 72-year-old
      woman with this syndrome is presented. High-dose intravenous gamma-globulin
      resulted in prompt resolution of her thrombocytopenia. The basic pathophysiologic
      mechanism of PTP is the development of an alloantibody to a human platelet
      antigen. The mystery of PTP is why the patients' own, as well as transfused PLA1
      negative platelets, are destroyed.

PMID- 7813929
TI  - [Who takes care of the clinic health team?].
AB  - To characterize the primary health care provided community clinic personnel, we
      investigated the primary health care obtained by staff at Kupat Holim clinics.
      21% of physicians working in these clinics were not registered with any primary
      health care physician, compared with 4.4% of other clinic workers (nurses,
      clerks, pharmacists, cleaning workers, etc.). 40% of the staff preferred to be
      treated by the clinic in which they worked, while 26% preferred treatment at a
      clinic near their homes. Excluding physicians, 73% of the staff would take
      medical problems to the primary care physician with whom they were registered.
      23% of physicians would consult a specialist directly with such problems, and 16%
      said they would confer with a medical acquaintance. 52% of physicians had not
      consulted any doctor in the previous year, compared with 17% of nurses and 11% of
      the office staff. 94% of all the staff studied were satisfied with the medical
      treatment they were receiving. When presented with various alternatives for
      health care provision, most preferred to do the choosing themselves.

PMID- 7813931
TI  - [The risk of hepatitis C virus infection in health care workers].

PMID- 7813932
TI  - [Confocal laser scanning of optic nerve and retina--a promising innovation in
      ophthalmology].

PMID- 7813930
TI  - [Nobel Prize winners in Medicine 1994].

PMID- 7813933
TI  - [Estrogen replacement therapy and breast cancer].

PMID- 7813934
TI  - [Gastric lymphoma--an infectious disease?].

PMID- 7813935
TI  - [Human T cell lymphoma/leukemia virus type I].

PMID- 7813936
TI  - [Vitamin status in the elderly].

PMID- 7813938
TI  - [Smoking and halacha].

PMID- 7813939
TI  - [Artificial sweeteners and their safety].

PMID- 7813940
TI  - [Carcino embryonic antigen].

PMID- 7813937
TI  - [Melatonin: a coordinating signal for human gonadotropins?].

PMID- 7813941
TI  - [When assumptions are insufficient].

PMID- 7813943
TI  - [Assessment of vital activity in geriatric patients].
AB  - 17 parameters of vital activity (VA) were scanned in 35 female and 12 male
      dependent geriatric patients (mean age 81). These included mental testing,
      Barthel score, lung function, urinanalysis, creatinine clearance, Hb, albumin,
      globulin and electrolytes, skin-folds, locomotion, presence of IHD, hemodynamic
      state, continence, infections, WBC and lymphocyte count, pressure sores and
      dysphagia, 4 main templates of VA deterioration identified were: IHD,
      hemisyndrome (due to CVA), vegetative state (post-CVA) and senile dementia
      (SDAT). The IHD template was characterized by marked variations in VA, ending in
      death due to cardiac complications (pulmonary edema, ischemia, etc.). In the 3
      other templates VA gradually deteriorated. Gradual declining VA allowed
      assessment of individual mortality prognosis. Assessment was by approximation of
      the computed exponent of the extrapolated VA curves; the longer the observation,
      the fewer the mistakes in assessment. Epidemiologic prognosis data of 48
      dependent patients is described; mean age was about 81 years. Hospitalization
      mean was 853.5 +/- 601 days and for patients with dementia, 1158.6 +/- 622.7
      days.

PMID- 7813942
TI  - [Cisplatin-based chemotherapy for advanced basal and squamous cell carcinomas].
AB  - The majority of basal cell (BCC) and squamous cell (SCC) carcinomas of the skin
      are curable by surgery and/or radiation. However, additional therapy is required
      when the tumor is locally advanced, or has metastasized. 4 men and 4 women (mean
      age 70, range 49-86) with advanced BCC and/or SCC were treated with cisplatin
      based chemotherapy. The disease was local in 4, local with regional lymph node
      involvement in 2, involved regional lymph nodes in 1 and was local with distant
      metastases in 1 patient. All were treated with a combination of cisplatin and 5'
      fluorouracil. 2 were treated in addition with a combination of cyclophosphamide,
      doxorubicin, and cisplatin (CAP). Complete pathological response was seen in 2/8
      and partial response in 4/8 with an overall response rate of 75%. There was tumor
      progression in 2. Survival of patients who responded was from 3-47 months (mean
      12). The 2 who did not respond to chemotherapy died within 1 and 3 months of
      treatment. Significant side-effects in 6 included myelotoxicity and transient
      renal toxicity. We conclude that chemotherapy is effective in advanced BCC and
      SCC of the skin and may have curative potential when combined with local therapy.

PMID- 7813944
TI  - [Intestinal obstruction due to phytobezoar in a Meckel's diverticulum].
AB  - Meckel's diverticulum is the most prevalent anomaly of the gastrointestinal
      tract, found in about 2% of the general population. Most are asymptomatic; but
      most frequent complications are intestinal obstruction, diverticulitis and lower
      gastrointestinal bleeding. A 33-year-old man was operated on for mechanical small
      bowel obstruction caused by a large Meckel's diverticulum filled with a
      phytobezoar. This mechanism of obstruction is rare. When the history of a patient
      without previous intestinal operations, as in this case, raises the possibility
      of phytobezoar, the probability of congenital anomaly is high.

PMID- 7813945
TI  - [Intestinal obstruction due to lupin phytobezoar in a child].
AB  - Phytobezoar is a rare cause of intestinal obstruction in children. A 7-year-old
      boy was operated on for intestinal obstruction due to a phytobezoar. An
      exceptionally large amount of Lupin seeds had been eaten a few hours before the
      onset of pain. lupin seeds have not been documented as a cause of phytobezoar.

PMID- 7813946
TI  - [Lithium-associated psoriasis].
AB  - A number of medications including clonidine, digoxin and beta-blockers have been
      reported to cause psoriasis. Lithium has also been implicated especially among
      women. We describe a 45-year-old man who developed diffuse psoriatic lesions 1
      year after treatment with lithium was started. Various topical dermatological
      preparations failed to alleviate the lesions. Several weeks after discontinuation
      of lithium the psoriasis resolved. We discuss the possible mechanisms for lithium
      associated psoriasis and alert clinicians to the possibility of this troublesome
      side-effect in lithium-treated patients, with or without a family history of
      psoriasis.

PMID- 7813947
TI  - [A case of self-circumcision].
AB  - A 29-year-old bachelor had immigrated from Uzbekistan to Israel 2 years before to
      improve his economic situation. He began drinking at the age of 20, and increased
      to 1-1.5 bottles of vodka a day. He was unable to keep a job more than a few
      months. When called up for limited military service, he thought that the army
      might be a solution for his employment problem. However, he felt that he would
      not be able to integrate into the army, and later into Israeli society, unless he
      was circumcised. The Ministry of Religion deferred his request for a religious
      circumcision because they did not consider him Jewish. Since he could not afford
      to pay for the operation, he read up on the procedure, drank a bottle of vodka as
      premedication, and tried to circumcise himself with a razor blade. Since he was
      unable to control bleeding, he applied to the hospital emergency room half an
      hour later, where the circumcision was completed and sutured. The psychiatric
      diagnosis was an unspecified personality disorder with psychopathic but not
      psychotic features.

PMID- 7813948
TI  - [Hemophilus influenzae meningitis despite vaccination].
AB  - An 18-month-old male previously vaccinated with 4 doses of HbOC developed
      meningitis caused by Hemophilus influenzae type B. Immunological status was
      normal and antibody titer to Hemophilus influenzae type b was in the normal range
      for immunized children. Meningitis due to this organism should be considered even
      in children who are fully vaccinated.

PMID- 7813949
TI  - [Improvement in scleroderma kidney with captopril].
AB  - In the past bilateral nephrectomy was often necessary in treating hypertensive
      scleroderma renal crisis. Since the availability of convertin enzyme inhibitors,
      many patients who were dialysis-dependent have recovered sufficiently to
      discontinue dialysis. We describe a 32-year-old woman with scleroderma who
      developed malignant hypertension and acute renal failure and required dialysis.
      She was treated aggressively with captopril and other agents. After 15 months,
      renal function improved and hemodialysis could be discontinued.

PMID- 7813950
TI  - [Our experience with diagnosis, evaluation and treatment of poststernotomy
      sternal wound infections].
AB  - During 1984-1992 162 patients with post-sternotomy sternal wound infections were
      treated. Between 0.4-5% of these undergoing sternotomy suffer from this
      complication which carries a mortality of about 50% when treated by conventional,
      nonsurgical methods. 80% of our patients had undergone aortocoronary bypass
      surgery and 11% valve replacement. Major risk factors identified for
      postoperative infection were prolonged mechanical ventilation, prolonged
      extracorporeal bypass, smoking, diabetes, obesity and chronic lung disease. Of
      152 patients who underwent surgery, 35 had recurrent infections, especially
      during the first years of the study. 10 were managed by conservative methods.
      Reconstruction of the chest wall was performed in 125, using pectoralis major
      flaps (74 cases), rectus abdominis muscle flaps (53), myocutaneous flaps (5) and
      omental flap (1). Our series demonstrates the importance of a comprehensive,
      multi-disciplinary approach in evaluating and stabilizing these often critically
      ill patients. Computed tomography together with sinography have proven to be of
      major importance in diagnosing the location and extent of sternal wound
      infections. Strict adherence to antibiotic protocols, radical debridement of
      infected bone and soft tissues and subsequent reconstruction with muscle flaps
      has enabled us to reduce recurrent infection and improve morbidity and mortality
      rates.

PMID- 7813951
TI  - [Death rate as a quality assurance tool].

PMID- 7813952
TI  - [Body temperature regulation in thermodynamic terms].

PMID- 7813953
TI  - [Hepatitis E virus infection].

PMID- 7813954
TI  - [Poststernotomy sternal wound infection].

PMID- 7813955
TI  - [Surgery for peptic ulcer disease: what is the procedure of choice? I: Elective
      surgery].

PMID- 7813957
TI  - [Coccidynia].

PMID- 7813958
TI  - [Amplification of trinucleotide repeats--a new mutation mechanism causing common
      genetic diseases].

PMID- 7813956
TI  - [Hallucinations--literature review].

PMID- 7813959
TI  - [Pulse oximetry: principles, applications and pitfalls].

PMID- 7813960
TI  - [Routine preoperative and preanesthetic evaluation--methods, cost and benefit].

PMID- 7813961
TI  - The ethics of assisted suicide.
AB  - The ethics of assisted suicide and the wisdom of changing public policy to
      support assisted suicide are considered from the perspective of the social work
      profession. The traditional social work value of client self-determination is
      reviewed and discussed, and tensions in this ideal and conflicts with another
      primary social work value--client well-being--are identified. The primacy of the
      client's well-being sometimes, in the professional judgment of the social worker,
      overrides a client's stated wish. This article finds assisted suicide unethical:
      Studies indicate that the judgment of most suicidal people is impaired as a
      result of depression or other mental illness. Truly "rational suicide" may exist
      but is probably quite rare compared to the overwhelming majority of suicides. In
      addition, assisted suicide may lead to increased rates of suicide in the general
      population, especially among young people, because of the contagion phenomenon
      and the destigmatization of suicide.

PMID- 7813963
TI  - Amyotrophic lateral sclerosis patients' perspectives on use of mechanical
      ventilation.
AB  - Thirteen persons diagnosed with amyotrophic lateral sclerosis were interviewed to
      determine the factors involved in making a decision whether to use mechanical
      ventilatory support. All study participants believed that they alone should make
      the decision regarding use of mechanical ventilation. The factors they considered
      to be of most importance were quality of life, severity of disability,
      availability of ventilation by means of a nasal mask, possible admission to a
      long-term care facility, ability to discontinue use of mechanical ventilation,
      desire to live, concern for their families' emotional health, and concern for
      care demands placed on their families. Suggestions are offered to facilitate the
      patient's decision-making process through provision of more information and
      improved dialogue between patient and professional.

PMID- 7813962
TI  - Patient self-determination and the artificial prolongation of life.
AB  - Ethical dilemmas are inherent in health care decision making. The Patient Self
      Determination Act of 1990 provides health care facilities with guidelines to
      address patients' advance directives. Family members who are charged with the
      responsibility to implement their loved ones' wishes often feel emotional
      conflicts because of the many difficulties that arise from making life and death
      decisions for another person. The PRACTICE model discussed in this article allows
      health care practitioners to think about ethical issues in a structured and
      systematic way. Social workers have a vital role to play in facilitating the
      implementation of patients' advance directives by working with the patient in
      creating clear and accurate directives, by supporting the family in allowing
      these directives to be carried out, and by working with the treatment team to
      resolve ethical dilemmas.

PMID- 7813964
TI  - A high-risk screen for psychiatric discharge planning.
AB  - This article tests the hypothesis that psychiatric inpatients at high risk for
      presenting difficulties in aftercare planning can be accurately identified on
      admission to an inpatient unit. A 16-item high-risk screening list is presented
      that was developed through an earlier analysis of discharge-delayed cases in a
      psychiatric hospital. The capacity of the list to accurately predict high-risk
      status was tested by comparing admission and discharge high-risk scores for 448
      patients with a range of psychiatric disorders. Sixty-six percent of the patients
      rated high risk at admission were identically rated at discharge. Differences
      among risk groups were also found with respect to key demographic variables. The
      high-risk screen permits early identification of patients who will require
      immediate and intensive environmental interventions. Such data are critical to
      psychiatric social work in preventing overstays and in deploying department
      resources with maximum effectiveness.

PMID- 7813965
TI  - Families of chronically mentally ill patients: their structure, coping resources,
      and tolerance for deviant behavior.
AB  - The attitudes of families toward caring for a mentally ill member in the home are
      explored through in-depth interviews with 105 families of chronically ill
      psychiatric patients from a public and a private hospital. Family readiness,
      defined as having the ability and the willingness to supervise the patient, was
      measured by the St. Paul Scale of Family Functioning and the Tolerance of Deviant
      Behavior Scale. Findings revealed a significant relationship between the
      respondent's belief in his or her ability to manage the behavior of the patient
      and willingness to accept the patient into the home as measured by tolerance for
      deviant behavior. No significant relationships were found between family
      resources, level of functioning, income, or community connectedness. Implications
      for practice and study limitations are discussed.

PMID- 7813967
TI  - Supports for community-based mental health care: an optimistic review of federal
      legislation.
AB  - For the past 50 years, federal legislation has been a key force in shaping the
      delivery of public mental health services. This article describes and summarizes
      recent relevant federal legislative initiatives and analyzes their potential in
      providing support, either explicit or implicit, for community-based mental health
      care for adults in the United States. These legislative mandates and options can
      be a source of optimism and ammunition for advocates and change agents as they
      continue to work vigorously to improve the mental health services system.

PMID- 7813966
TI  - Mental health under national health care reform: the empirical foundations.
AB  - This article reviews research pertinent to mental health services under several
      U.S. health care reform proposals. Issues examined include the redistributional
      impact of the inclusion of outpatient mental health benefits, optimal benefit
      packages, and findings that mental health services lower medical utilization
      costs. It is argued that extending a minimalist model of time-limited benefits,
      similar to that implemented in most managed care programs, to a national health
      care insurance plan would perpetuate the current two-class mental health care
      system.

PMID- 7813968
TI  - Social work delivery of hospital-based financial assistance services.

PMID- 7813969
TI  - Patient rights and dying: policy restraint and the states.

PMID- 7813970
TI  - Phylogeny of the lemuridae revisited: evidence from communication signals.
AB  - Phylogenetic relationships among the extant lemurid prosimians were assessed
      cladistically using stereotyped vocal, olfactory, and visual communication
      characters. Among our results are 3 findings of particular importance. First, our
      data are consistent with those from several recent studies of highly repeated DNA
      fragments in supporting a close phyletic affinity between Lemur catta and the
      genus Hapalemur. Moreover, our results indicate that L. catta is nested within
      the Hapalemur clade as the sister taxon to Hapalemur griseus/Hapalemur aureus. We
      interpret character states shared between Hapalemur simus and L. catta as
      primitive retentions by L. catta. Second, our findings agree with the DNA data in
      proposing a sister group relationship for Eulemur coronatus and Eulemur
      rubriventer. Third, our results question the validity of assigning Varecia
      variegata to the Lemuridae. For the characters we examined, Varecia more
      resembled indrids than lemurids, and the position of Varecia could be swapped
      with any of our outgroups (Indri, Propithecus, Daubentonia) without affecting
      tree topology. Previous workers sometimes have linked Varecia with various
      lemurids on grounds of ambiguously defined characters or on incorrect data
      gleaned from the literature. In those studies, the placement of Varecia in the
      Lemuridae usually has depended more on the minimization of character state
      conflicts (i.e. parsimony), than on demonstrable synapomorphies. In addition,
      data from DNA research have failed to demonstrate any pattern that links Varecia
      with Lemur, Hapalemur, or Eulemur. Results of the present study suggest that
      shared Varecia-indrid character states may be symplesiomorphic retentions in the
      Indridae, and that Varecia could be phyletically more primitive than either the
      indrids or lemurids.

PMID- 7813971
TI  - Feeding behaviour and activity patterns of two Malagasy bamboo lemurs, Hapalemur
      simus and Hapalemur griseus, in captivity.

PMID- 7813972
TI  - A new form of tool use by orang-utans in Sabah, East Malaysia.

PMID- 7813973
TI  - [Morphogenesis of the femoral diaphysis in humans: significance of function and
      evolution].
AB  - The obliquity of the femoral diaphysis, measured by the bicondylar angle, permits
      the adducted position of the knee in humans. The presence of a high femoral
      bicondylar angle has been a hallmark of hominid bipedality, but its pattern of
      development has not been documented. We have observed radiographic and skeletal
      data on the development of this angle. The two samples exhibit a pattern of a
      bicondylar angle of 0 degrees at birth and then a steady average increase in the
      angle through infancy and into the juvenile years. These data establish a high
      degree of potential for plasticity in the development of this angle and the
      direct association of a bipedal locomotion with the developmental emergence of a
      human femoral bicondylar angle. We show that the obliquity angle, which
      occasionally appears in some non-human primates, is not homologous to the human
      condition. As this angle is an epigenetic functional feature in modern humans, we
      suggest that it developed following a change in infantile locomotor behaviour of
      the early australopithecines and was not the result of a genomic change.

PMID- 7813974
TI  - Sexual dimorphism in Notharctid primates.

PMID- 7813975
TI  - Functional significance of the fibula: contrasts between humans and chimpanzees.

PMID- 7813976
TI  - Lack of correlation between body size and frequency of vocalizations in young
      female Japanese macaques (Macaca fuscata).

PMID- 7813978
TI  - An ambitious baboon: independent rise in rank by a single female.

PMID- 7813977
TI  - Intergroup grooming relations between alpha females in a population of free
      ranging rhesus macaques.
AB  - Intergroup affiliation among female rhesus macaques, Macaca mulatta, was examined
      in the captive free-ranging colony of Morgan Island, S.C., USA. The provisioned
      colony has many social groups (35) and is maintained at a relatively high
      population density (21 animals/ha) with a relatively low adult male to female
      ratio (1:8.8). Focal and ad libitum samples were collected on 32 adults (3 males
      and 29 females) from two groups. Although infrequent, grooming was observed
      between adult females from different groups, and alpha females were the main
      participants in these interactions. Colony records indicated that none of the
      intergroup grooms was between females formerly from a common group. Relations
      between familiar neighboring groups may be maintained by a combination of both
      affiliative and aggressive behavior.

PMID- 7813979
TI  - Vocalizations of captive Francois' langurs linked to stereotypy and possible
      stress.

PMID- 7813980
TI  - Asymmetrical manipulation in the use of tools by tufted capuchin monkeys (Cebus
      apella).

PMID- 7813981
TI  - Study on the carcinogenicity of tannic acid in F344 rats.
AB  - The carcinogenicity of tannic acid, a compound that is used as a food additive, a
      clarifying agent and a refining agent, was examined in F344 rats of both sexes.
      Tannic acid was dissolved in distilled water at concentrations of 0.25 and 0.5%.
      The doses were selected on the basis of results from a 13-wk subchronic study.
      Groups of 50 male and 50 female rats were given one of these solutions ad lib. as
      their drinking water for up to 2 yr. The mean body weights of the treated males
      were essentially comparable with those of the controls, whereas treated females
      had lower mean body weights than the control group. A variety of tumours
      developed in all groups, including the control group, but all the neoplasms were
      histologically similar to those known to occur spontaneously in this strain of
      rats, and no statistically significant increase in the incidence of any tumour
      was found in the treated groups of either sex. Thus, it is concluded that, under
      the conditions of the experiment, tannic acid has neither carcinogenic potential
      in F344 rats nor modifying effects on spontaneous tumour development.

PMID- 7813982
TI  - Comparison of the toxicity of cinnamaldehyde when administered by
      microencapsulation in feed or by corn oil gavage.
AB  - The toxicity of cinnamaldehyde (CNMA) was compared after administration by gavage
      and in dosed feed. Rats and mice of both sexes received CNMA by daily corn oil
      gavage (for 2 wk), or in microencapsulated form in feed (2 wk for rats, 3 wk for
      mice). Feed formulations contained 0-10% CNMA microcapsules, equivalent to
      approximate daily doses of 0-3000 mg CNMA/kg body weight for rats and 0-10,000 mg
      CNMA/kg body weight for mice. Concentrations were chosen to deliver CNMA doses
      approximately equal to doses in the gavage study. Gavage doses of 2620 mg/kg/day
      and above in mice and 940 mg/kg/day and above in rats produced nearly 100%
      mortality; there were no deaths in animals receiving microencapsulated CNMA. Rats
      and mice receiving CNMA in feed showed a dose-related decrease in body weight
      gain, which was accompanied in rats by hypoplastic changes in reproductive organs
      and accessory sex glands. CNMA administration by either route caused hyperplasia
      of the forestomach mucosa. These results demonstrate that microencapsulation in
      feed can present a useful alternative to gavage dosing for repeated-dose or
      prolonged-exposure studies, in that (1) the toxic effects of CNMA were similar
      after gavage dosing and after administration in microencapsulated form in feed,
      (2) ingestion of chemical in the feed more closely approximates human exposures,
      and (3) microencapsulation allows the delivery of higher net doses of chemical,
      while avoiding the acutely toxic effects of a bolus dose.

PMID- 7813983
TI  - N-nitroso compounds in two nitrosated food products in southwest Korea.
AB  - Gastric cancer is the commonest malignant neoplasm in Southwest Korea. The
      possibility of carcinogenic dietary factors led to the investigation of exposure
      to N-nitroso compound precursors among residents of the City of Chonju and of two
      outlying rural townships in North Cholla Province. Two traditional and widely
      consumed home-prepared food products, salted pickled cabbage (kimchi) and salted
      seafood sauce (chut-kal) were analysed (a) for nitrite, nitrate, total secondary
      amines and pH in these food products prior to nitrite incubation and (b) for
      volatile nitrosamines and total N-nitroso compounds before and after incubation
      with nitrite in simulated human stomach conditions. Nitrate levels were
      significantly higher in kimchi (median 1550 mg/kg) than in chut-kal (median 140
      mg/kg) (P < 0.001). Secondary amine levels in non-nitrosated samples of kimchi
      (median 5.5 mg/kg) were significantly lower than secondary amine levels in non
      nitrosated chut-kal (median 56 mg/kg) (P = < 0.001). Analyses of nitrite
      incubated kimchi revealed high levels of total N-nitroso compounds (median 1173
      micrograms/kg); the increase with nitrosation was significant (P = 0.001). The
      concentration of N-nitroso compounds in nitrite-incubated kimchi was
      significantly greater than that found in nitrite-incubated chut-kal (P = 0.015).
      The combination of high levels of nitrate in the kimchi, the demonstration of
      high levels of total N-nitroso compounds in this food after nitrosation, and the
      volume of kimchi consumed in the traditional diet suggest that salted pickled
      cabbage may play a role in gastric carcinogenesis in Southwest Korea.

PMID- 7813984
TI  - Flow cytometric analysis of the effects of in vitro exposure to vomitoxin
      (deoxynivalenol) on apoptosis in murine T, B and IgA+ cells.
AB  - The immunotoxic effects of the trichothecene vomitoxin (VT or deoxynivalenol) and
      other trichothecenes may be mediated by direct interaction with lymphocytes. In
      this study, flow cytometric cell cycle analysis was used in conjunction with
      phenotypic staining by specific fluorescein isothiocyanate antibody conjugates to
      assess the in vitro effects of VT and another protein synthesis inhibitor,
      cycloheximide (CHX), on apoptosis in specific T- and B-cell subsets within
      thymus, spleen and Peyer's patch (PP) cultures. Both VT and CHX markedly
      inhibited T-cell apoptosis in dexamethasone (9 alpha-fluoro-16 alpha
      methylprednisolone)-induced (DEX+) cells isolated from thymus, spleen and PP.
      Apoptosis-associated internucleosomal DNA fragmentation in whole thymus cell
      lysates as measured by gel electrophoresis was qualitatively consistent with flow
      cytometry among the various treatment groups. VT and CHX induced apoptosis in
      untreated (DEX-) T, B. and IgA+ cells from spleen and PP, whereas the effects of
      VT and CHX on DEX-induced apoptosis in B and IgA+ cells from these sources were
      negligible. These findings indicate that VT could either inhibit or enhance
      programmed cell death in a concentration-dependent manner and that this was
      dependent on lymphocyte subset, tissue source and glucocorticoid induction.

PMID- 7813986
TI  - A competitive enzyme-linked immunoassay for domoic acid determination in human
      body fluids.
AB  - A polyclonal antiserum was raised in mice against domoic acid. Two of three
      immunogens consisted of domoic acid coupled to ovalbumin (OVA) and keyhole limpet
      haemocyanin at molar ratios of 47:1 and 44:1, respectively using a carbodiimide
      reaction. Titres of both antisera exceeded 1/35,000 against domoic acid coupled
      to the non-relevant carrier. Domoic acid was also conjugated to bovine serum
      albumin at a molar ratio of 30:1 using N-hydroxysuccinimidyl-4-azidobenzoate, a
      photoreactive compound. This immunogen, however, produced no measurable serum
      titres against domoic acid. The antiserum produced against the OVA conjugate
      displayed the highest affinity for free domoic acid in competitive enzyme-linked
      immunosorbent assay (ELISA). Furthermore, this antiserum preparation did not
      significantly cross-react with glutamic acid, aspartic acid, the structural
      analogue kainic acid, or the paralytic shellfish toxin, saxitoxin. The
      competitive ELISA was used to quantify domoic acid concentrations in human body
      fluids spiked with pure domoate. The lower limits of accurate domoic acid
      determinations in competitive ELISA were 0.2 micrograms/ml in urine, 0.25
      micrograms/ml in plasma and 10 micrograms/ml in milk. It was concluded that the
      competitive ELISA described herein could be used to quantitate directly the
      concentration of domoic acid in the body fluids of individuals with amnesic
      shellfish poisoning.

PMID- 7813985
TI  - Disposition and metabolism of radiolabelled pentachloroanisole in rats and
      rabbits.
AB  - Male Sprague-Dawley rats and New Zealand White rabbits were administered 14C
      labelled pentachloroanisole (PCA) in corn oil by gavage as single doses of 25
      mg/kg and were then placed in individual metabolism cages for as long as 4 days.
      Peak blood level of radioactivity occurred 6 hr after administration of the dose
      to rats and between 3 and 4 hr in rabbits; the blood elimination half-life ranged
      from 8 to 15 hr in rats and averaged 6 hr in rabbits. Rats excreted an average of
      54.2% of the administered radiolabel in the urine and 32.4% in the faeces during
      the 96 hr following the dose; rabbits excreted an average of 84.2 and 13.1% of
      the radiolabel in the urine and faeces, respectively, during this time.
      Examination of the metabolites in the rat showed that 60% of the urinary
      radioactivity was attributable to tetrachlorohydroquinone (TCH), 3% to free
      pentachlorophenol (PCP) and 29% to conjugated PCP; faecal metabolites were PCP
      (85.7%), TCH (4.3%) and polar metabolite(s) (10%). In the rabbit, 58% of the
      urinary radioactivity was attributable to TCH, 8% to free PCP and 34% to
      conjugated PCP. Faecal metabolites consisted of PCP and conjugated material.

PMID- 7813987
TI  - Development of a 10-day chorioallantoic membrane vascular assay as an alternative
      to the Draize rabbit eye irritation test.
AB  - The chorioallantoic membrane (CAM) of a fertilized hen's egg has been studied
      extensively as a promising alternative model for predicting eye irritation
      potential. The specific methodology used with this model has varied among
      investigators but the basic premise of applying test material to the membrane
      surface and evaluating changes in the vasculature is relatively consistent. The
      CAM vascular assay (CAMVA) has shown high correlation with in vivo rabbit eye
      irritation data. This method uses the CAM of a 14-day-old egg and the response at
      30 min after treatment as the endpoint. The primary CAM methods being evaluated
      in Europe use 9-10-day-old eggs because older eggs are considered 'live animals';
      the possibility of using 10-day-old eggs to make the method more globally
      acceptable as a non-animal test was therefore investigated. By keeping the
      original CAMVA dosing and evaluation procedures the same, and only altering the
      age of the eggs from 14-day to 10-day, the results were found to be nearly
      identical for the two methods and both produce equivalent correlations to the in
      vivo eye irritation test results. Maintaining the original CAMVA methodology but
      using a younger egg, therefore, provides a good alternative method for predicting
      eye irritation potential that is more globally acceptable as a non-animal test.

PMID- 7813988
TI  - Modified suspension Ames test for testing proteinaceous substances: an initial
      step.
AB  - The basic Salmonella/microsome assay (Ames test) is a valuable primary tool by
      which to discriminate mutagens from non-mutagens. For a variety of chemical test
      substances this test is easily conducted according to international guidelines
      for genotoxicity testing. However, the testing of proteinaceous substances in the
      basic Ames test may generate false positives owing to the presence of growth
      promoting constituents in the test sample, such as histidine or its precursors.
      It was hypothesized that the growth-promoting capacities of biological test
      samples might be overcome by testing according to the 'suspension variant' of the
      Ames test, which uses very rich growth conditions thereby overwhelming any growth
      enhancing constituents present in a biological test sample. This hypothesis
      appeared to be correct, although several important modifications had to be made
      to the suspension assay. The most important aspect of this 'new suspension Ames
      test' appeared to be the plating of overnight regrown bacteria in the poorest way
      possible (by omitting histidine and nutrient broth from the overlay agar). This
      study may comprise an initial step in the development of a modified suspension
      Ames test for testing proteinaceous substances.

PMID- 7813989
TI  - Inhibition of malondialdehyde formation from liver microsomes by a lichen
      constituent.

PMID- 7813991
TI  - Biological effects of cosmetic talc.
AB  - A review of the literature reveals two primary issues: (1) a weak, but not
      causal, association of hygienic use of cosmetic talc and ovarian cancer; (2) lung
      changes in animals exposed to talc aerosol concentrations that resulted in lung
      overload. The evidentiary weight of the most significant of the epidemiological
      and laboratory studies and their biological significance for human risk
      assessment are briefly discussed. Publications describing granulomatous lesions
      attributed to talc on surgical gloves, and consequences of accidental inhalation
      of baby powder by infants are also reviewed. The literature reviewed does not
      provide any convincing evidence that pure cosmetic talc, when used as intended,
      presents a health risk to the human consumer.

PMID- 7813992
TI  - Impurity profiling analysis of illicit drug. Mini-reviews presented at the
      International Symposium of Forensic Science. Tokyo, Japan, 21-22 October 1993.

PMID- 7813990
TI  - Effect of grapefruit juice on drug metabolism in rats.
AB  - The effect of grapefruit juice on in vivo drug metabolism was investigated in
      rats. The juice (4 ml or 8 ml/kg) was given orally once daily for 2 consecutive
      days and its effect on theophylline metabolism, pentobarbitone sleeping time and
      the tremorgenic action of tremorine was studied. The effect of grapefruit juice
      on some of these parameters was compared with that of the known drug metabolism
      inhibitor cimetidine given ip. Grapefruit juice at 4 ml and 8 ml/kg produced
      significant increases in pentobarbitone sleeping time that reached 46 and 79%,
      respectively, compared with 107% produced by cimetidine (50 mg/kg, ip). The juice
      at 4 ml/kg also significantly increased plasma theophylline concentration when
      measured 15, 30, 60 and 90 min after ip theophylline administration (10 mg/kg).
      Thereafter, no significant differences were detected in plasma drug
      concentrations between juice- and saline-treated animals. Administration of
      tremorine (25 mg/kg, ip) to saline-treated controls produced, within 2 or 3 min,
      tremors, piloerection, profuse salivation, defaecation, urination and
      chromodacryorrhesis (red tears). The onset of appearance of these signs was
      delayed to about 7 min in rats pretreated 1 hr earlier with either grapefruit
      juice (4 ml/kg, orally) or cimetidine (50 mg/kg, ip). The severity of the above
      signs was markedly reduced to a similar extent in both the juice- and cimetidine
      treated rats. These results suggest that grapefruit juice may act as an inhibitor
      of drug metabolism in rats, and that its consumption may alter the disposition of
      certain concomitantly administered drugs.

PMID- 7813993
TI  - Fatalities due to intestinal obstruction following the ingestion of foreign
      bodies.
AB  - Two fatalities due to an occlusive ileus following the ingestion of foreign
      bodies in patients with psychiatric disorders are described. A severely mentally
      handicapped young man developed a temperature and died 1 h after admission to a
      surgical ward. At autopsy, approximately 2000 cm3 of foreign material, including
      broken glass and porcelain, branches, buttons, parts of clothing and other
      material were found in the gastrointestinal tract, leading to a complete
      obstruction of the distal intestine and colon with resulting faecal vomiting. The
      other case was even more unusual as hair fetishist had swallowed a thick strand
      of his own hair, 50 cm long, also resulting in mechanical obstruction of the
      distal intestine.

PMID- 7813994
TI  - The ability of dogs to recognize and cross-match human odours.
AB  - The Dutch police use specially trained dogs, Canis familiaris, to identify
      criminals from scented objects left at the scene of the crime. As part of a study
      of the reliability of these identifications, experiments were performed to
      evaluate whether these dogs could match scents collected from different parts of
      the body. Dutch police dogs are capable of matching hand scent to scent collected
      in the crook of the elbow and vice versa, and of matching trouser pocket scent to
      hand scent. It appears that training and familiarity with the person whose scents
      have to be matched enhance the performance of the dogs. The reliability for
      judicial purposes entails further research since our knowledge of the sense of
      smell is limited.

PMID- 7813995
TI  - Guidelines for estimating the amount of alcohol consumed from a single
      measurement of blood alcohol concentration: re-evaluation of Widmark's equation.
AB  - This article deals with the pharmacokinetics of ethanol and the reliability of
      estimating the amount of alcohol ingested from a single measurement of a person's
      blood alcohol concentration (BAC). Blood alcohol curves were plotted for 108 male
      subjects after they drank various doses of ethanol (0.51-0.85 g/kg body weight).
      The rate of disappearance of ethanol from the blood (beta-slope) and the apparent
      volume of distribution of ethanol (Widmark's rho factor, rho) were calculated for
      each subject; the mean beta-slope was 13.3 mg/dl/h (SD = 2.0), and the mean rho
      factor was 0.689 l/kg (SD = 0.061). The value of beta increased slightly with
      increasing dose of alcohol (P < 0.05). The blood alcohol parameters beta and rho
      were negatively correlated (r = -0.135). The BACs measured at 2 h and 5 h post
      drinking were used to estimate the amount of alcohol each subject had consumed
      according to the method proposed by Widmark [1]. The mean differences (estimated
      actual) and the +/- 95% limits of agreement were -0.72 g (+/- 12), and 2.2 (+/-
      15), for the 2 h and 5 h BAC values, respectively. A method based on error
      propagation was used to derive the 95% limits of uncertainty in the amount of
      alcohol ingested. On the basis of a single measurement of BAC, we could estimate
      the amount of alcohol ingested within +/- 20%.

PMID- 7813996
TI  - Production of monoclonal antibody reactive with leukotoxin and its
      immunohistochemical application.
AB  - A sensitive enzyme-linked immunosorbent assay (ELISA) using a monoclonal antibody
      (ALM-1) was developed for the determination of leukotoxin (9,10-epoxy-12-
      octadecenoic acid), which was reported to exist in human burned skin and
      neutrophils, and was regarded as a toxic and/or defensive substance in living
      beings. The leukotoxin was conjugated with bovine serum albumin (BSA) by means of
      the mixed anhydride technique as immunogen, and BALB/c mice were immunized over 6
      months. The detection limit of leukotoxin was at least as low as 5 ng in this
      ELISA. This antibody had a strong specificity to leukotoxin and no cross
      reactivity with the other analogs tested, and was usable for an
      immunohistochemical application. By using the antibody, leukotoxin was
      immunohistochemically observed not only in neutrophils, but also in alveolar
      macrophages in an oxygen-exposured rat lung.

PMID- 7813997
TI  - Biventricular measurement of blood strontium in real cases of drowning.
AB  - A simple method for blood strontium determination by spetrophotometry atomic
      absorption with Zeeman correction is proposed. This method is applied to real
      cases of death by drowning, where the difference in blood strontium concentration
      between the left and the right side of the heart could contribute, together with
      other data, to the investigation of causes of death in cases of drowning in salt
      water. The differences obtained in blood strontium concentrations between the
      left and the right side of the heart in cases of supposed 'typical drowning' in
      sea water were always > 75 micrograms Sr/l, compared to < 20 micrograms Sr/l
      found in two supposed cases of 'atypical drowning'.

PMID- 7813999
TI  - An investigation of the HUMVWA31A locus in British Caucasians.
AB  - A number of short tandem repeat (STR) loci are currently being examined for their
      usefulness as markers of identity; HUMVWA31A is one such locus. We used a high
      sieving agarose technique to type 200 British Caucasians for this locus.
      Comparison of the resultant allele frequencies with other published databases
      showed that their distributions were similar. Observed heterozygosity was similar
      to that reported in other population studies but significantly lower than
      expected. A goodness of fit analysis of observed and expected genotypes was
      highly significant, suggesting a deviation from Hardy-Weinberg equilibrium,
      although reports from other populations appeared not to show such differences.
      The possibility that mistyping had led to an erroneous statistic was investigated
      by detailed examination of samples within our own laboratory and in two other
      laboratories, involving verification of the agarose typing by both automated
      fluorescent detection techniques, and sequencing. Other reported deviations from
      Hardy-Weinberg equilibrium in STR systems are discussed.

PMID- 7813998
TI  - Estimation of age at death based on aspartic acid racemization in noncollagenous
      bone proteins.
AB  - Age at death determination based on the extent of aspartic acid racemization in
      dentin has been reported to be highly accurate and reproducible. To test the
      applicability of this method to human bone, aspartic acid racemization in
      noncollagenous proteins of bone was investigated. A close relationship was found
      between age at death and the extent of aspartic acid racemization in osteocalcin,
      the most abundant noncollagenous protein of the organic bone matrix. Our findings
      indicate that osteocalcin is a permanent, 'aging' constituent of the organic bone
      matrix whose D-aspartic acid content increases with age because of in vivo
      racemization. Thus, the extent of aspartic acid racemization in bone osteocalcin
      is a measure of the age of the peptide and hence of the entire organism. The
      relationship between age at death and the extent of aspartic acid racemization in
      purified bone osteocalcin appears to be close enough to serve as a basis for
      determination of age at death in forensic medicine.

PMID- 7814000
TI  - Frank A. Beach Award. Estrogens to song: picograms to sonograms.

PMID- 7814001
TI  - Low temperatures affect the photoperiodically induced LH and testicular cycles
      differently in closely related species of tits (Parus spp.).
AB  - Photosensitive great tits (Parus major) and willow tits (P. montanus) were
      exposed to long days (20L:4D) under three different temperature conditions (4+,
      +10, and +20 degrees C) in early winter. The two species showed significant
      differences in their LH and testicular reaction patterns to low temperatures.
      Testes showed pronounced growth cycles under all temperature regimes. For the
      willow tit, testes in birds kept at +20 degrees C reached maximum size about 2
      weeks earlier than testes in birds living under the two lower temperature
      regimes, whereas in the great tit testes reached maximum size at about the same
      time in all three groups. Low temperatures delayed the onset of testicular
      regression in both species. Plasma levels of LH did change with time in both
      species. However, the patterns of the induced LH-cycles in the three great tit
      groups differed significantly from each other, whereas this was not the case for
      the willow tits. The LH cycle was especially pronounced in great tits kept at +20
      degrees C. The initial LH peak in great tits kept at +4 and +10 degrees C was
      about 50% lower than in great tits kept at +20 degrees C. These results are
      discussed in relation to species differences in winter ecology and establishment
      of breeding territories.

PMID- 7814002
TI  - Gender and intrauterine position influence saccharin preference in mice.
AB  - Gender differences in saccharin preference in adult Rockland-Swiss mice were
      examined in Experiment 1. Separate groups of male and female mice received tap
      water and one of five concentrations of saccharin solution (either 0.10, 0.25,
      0.50, 0.75, or 1.00%). A significantly higher preference score was obtained for
      females vs. males that received the 0.25% solution. Other concentrations did not
      yield a significant sex difference. The purpose of Experiment 2 was to examine
      prenatal influences on preference patterns of adult males. Mice were delivered by
      cesarean section and classified as having resided between two male (2M), two
      female (0M), or one male and one female (1M) fetuses. Saccharin preference was
      then examined in separate groups of adult males that received either a 0.25 or a
      0.75% solution. A significantly higher preference score was obtained for 0M vs.
      2M males that received the 0.25% concentration; no difference was obtained with
      the 0.75% solution. Differences between 2M and 0M males may be due to the actions
      of prenatal steroids.

PMID- 7814003
TI  - Effects of testosterone exposure and fighting experience on the aggressive
      behavior of female and male mice selectively bred for intermale aggression.
AB  - Exposure of female mice to testosterone resulted in aggressive behavior as a
      function of breeding line in two lines of mice selectively bred for high (Turku
      Aggressive, TA) and low (Turku Nonaggressive, TNA) levels of aggressiveness.
      Female TA mice that received a single injection of testosterone propionate (TP)
      (1 mg in 0.05 ml peanut oil) on the second day of life, and starting at 120 days
      of age received daily injections for seven consecutive days, displayed aggressive
      behavior on a level comparable to that of socially isolated males of the same
      line, whereas control TA females (injected with 0.05 ml peanut oil) and TP
      exposed TNA females were totally nonaggressive. The level of aggressiveness was
      assessed by means of dyadic tests against intact male opponents. Early and adult
      exposure to TP did not lead to increased aggressiveness in male TNA mice.
      Fighting experience in combination with prolonged TP treatment changed the
      aggressiveness of the TP-exposed TA females, leading to decreased aggressiveness
      in defeated animals. The genetically correlated low level of aggressiveness of
      TNA male and female mice was unaffected by any combination of TP exposure,
      learning and social isolation. It is concluded that differences in testosterone
      reactivity of target organs, other than those which are Y chromosome determined,
      i.e., the testes, are responsible for the aggressiveness in the strains studied.

PMID- 7814004
TI  - Arginine vasotocin facilitation of advertisement calling and call phonotaxis in
      bullfrogs.
AB  - Although the neuropeptide arginine vasotocin (AVT) is found in several auditory
      and vocalization regions of the bullfrog (Rana catesbeiana) brain, its functions
      in these areas are unknown. We examined the effects of AVT injection on two
      auditory-evoked reproductive behaviors: advertisement calling in male bullfrogs
      and call phonotaxis in female bullfrogs. AVT (500 micrograms; intraperitoneal)
      significantly increased advertisement call frequency and decreased calling
      latency in male bullfrogs, compared to saline injection. This dose of AVT also
      significantly decreased the time required for female bullfrogs to reach a call
      source as well as the latency of females to leave the starting position during
      call playback. In both males and females, these effects were significant at 0.5
      hr and persisted until at least 2 hr after injection. AVT thus facilitated
      display of two sexually-dimorphic reproductive behaviors in bullfrogs. These
      effects may be due to direct effects of AVT on auditory processing regions in the
      bullfrog brain.

PMID- 7814005
TI  - Effect of prepubertal ovariectomy on amphetamine-induced locomotor activity in
      adult female rats.
AB  - Adult female rats show greater behavioral activation in response to both acute
      and repeated injections of amphetamine (AMPH) than adult male rats. The present
      experiments investigated whether life-long exposure to ovarian hormones in
      females contributes to their enhanced responsiveness to AMPH as adults and
      whether this effect depends on exposure to testosterone (T) in the neonatal
      period. In Experiment 1, female rats were ovariectomized either prior to puberty
      (EARLY) or in adulthood (ADULT). Locomotor activity in response to either 1.5
      mg/kg AMPH or the saline vehicle was measured for 2 hr every third day on five
      occasions. On the sixth occasion all animals received 0.75 mg/kg AMPH in a test
      for sensitization. Each animal received either 5.0 micrograms estradiol benzoate
      (EB) or the oil vehicle (OIL), 30-35 min prior to each session. Experiment 2 was
      similar except that all animals were treated with T at birth. In Experiment 1,
      during the repeated treatment period, group EARLY had lower AMPH-induced activity
      scores than group ADULT, in both OIL and EB conditions. EB-treated rats had
      higher levels of AMPH-induced activity and showed greater changes in activity
      over days of testing than OIL-treated rats, regardless of time of ovariectomy.
      Animals previously exposed to AMPH showed higher levels of activity on the test
      for sensitization than animals receiving the drug for the first time, but this
      effect did not vary as a function of hormone condition or time of ovariectomy.
      Exposure of females to T at birth reduced responsiveness to AMPH and EB in
      adulthood, and ovariectomy prior to puberty had little effect in these animals.

PMID- 7814006
TI  - Methyl farnesoate levels in male spider crabs exhibiting active reproductive
      behavior.
AB  - The concentration of methyl farnesoate (MF) in the hemolymph and its synthesis by
      the mandibular organs (MOs) were investigated to determine whether this compound
      is related to the differences in the size of the reproductive system and the
      mating behavior among male morphotypes of the spider crab, Libinia emarginata.
      Large-claw abraded males displayed mating behavior under competitive conditions.
      They have the largest reproductive systems, their MOs synthesize large amounts of
      MF in vitro, and the concentration of MF in their hemolymph is high. Small-claw
      abraded males displayed mating behavior with receptive females only when
      isolated. These smaller crabs have intermediate-sized reproductive systems, their
      MOs synthesize the most MF, and they have the highest circulating level of MF
      relative to their body size. The unabraded males did not display mating behavior;
      their reproductive systems are smaller; their MO activity is low, as is their
      circulating level of MF. The strong relationship between MF levels and the
      intensity of reproductive behavior suggests that MF may be one of the driving
      forces behind mating behavior in Crustacea.

PMID- 7814007
TI  - Effects of steroid hormone interaction on activity and home-range size of male
      lizards.
AB  - Steroid hormones play a major role in influencing the physiology and behavior of
      all animals, including reptiles. Oftentimes, it is an interaction between two or
      more hormones that is ultimately responsible for the observed response or
      behavior. We designed a pair of field studies on adjacent communities of side
      blotched lizards (Uta stansburiana) to provide insight into the interrelationship
      of testosterone (T) and corticosterone (B) in regulating aggressive behavior. On
      one site, males were implanted with either T or saline (S), while on the other
      site males received either two S implants or both a T and a B implant (T + B). T
      increased both activity (by 31%) and home-range size (by 150%), whereas S
      implanted cohorts exhibited a reduction in both of these parameters (by 24 and
      50%, respectively). However, when B was given in combination with T, not only
      were the positive effects of T eliminated, but there was a reduction in activity
      (31%) and home-range size (72%) similar to that reported in lizards that received
      B implants alone. S-implanted cohorts in the T + B experiment increased their
      activity and home-range size by 15 and 43%, respectively. Although these latter
      changes in the S-implanted males are not statistically significant, they are
      indicative of a compensatory increase similar to that seen in the T and
      previously reported B outcrop experiments. Taken together, these results
      illustrate that regulation of aggressive behavior is complicated, with both
      hormonal and social interactions playing critical roles in determining an
      individual's home-range size and, hence, reproductive success.

PMID- 7814008
TI  - Infusion of an oxytocin antagonist into the medial preoptic area prior to
      progesterone inhibits sexual receptivity and increases rejection in female rats.
AB  - Central administration of an antagonist to the neuropeptide oxytocin (OT) has
      been shown to block the progesterone-induced facilitation of female sexual
      receptivity. In this study we examined the effects of infusing an OT antagonist
      (OTA) into various brain sites before rats were injected with 250 micrograms
      progesterone (P). Ovariectomized animals were injected daily for three
      consecutive days with 1 microgram estradiol benzoate and then on the fourth day
      were infused into the medial preoptic area (MPOA), medial basal hypothalamus
      (MBH) or ventral tegmental area with either 250 ng/microliter/side OTA or
      artificial cerebrospinal fluid vehicle. Animals were tested in an arena made of
      two white polyethylene cages connected by a tunnel that allowed passage of the
      female but not of the larger male. Several receptive and non-receptive behaviors
      were recorded for a 15-min period beginning 4 hr after P injection. Animals
      infused with OTA into the MPOA before P showed an increase in the frequency and
      total duration of fighting with males and the frequency of audible vocalizations
      made by females. OTA infusions also increased the frequency of mounts that did
      not result in a lordosis posture. OTA infusions into the MPOA also reduced the
      frequency and total duration of lordosis postures in response to mounts. OTA
      infusions into the MBH and VTA had no effect on measures of sexual behaviors.
      Blocking OT transmission in the MPOA resulted in increased rejection behaviors
      and decreased receptivity in females when infused before systemic P injection.

PMID- 7814009
TI  - Anorexia nervosa viewed as an extreme weight condition: genetic implications.
AB  - In anorexia nervosa, psychopathological features and reduced body weight are
      inseparable, suggesting a prominent role of behavioral factors in achievement and
      maintenance of extreme underweight. Due to the considerably higher prevalence of
      this eating disorder in females, anorexia nervosa contributes to the left end of
      the distribution of the body mass index, especially in the female sex. By
      reviewing the relevant literature we examined whether genetic research in
      anorexia nervosa can profit from considering this disorder as an extreme weight
      condition. For this purpose we compared genetic studies pertaining to both
      anorexia nervosa and the heritability of the body mass index. Whereas previous
      genetic studies in anorexia nervosa have mostly concentrated on the assessment of
      the familial psychopathology, further studies are warranted that additionally
      attempt to analyze the complex phenotype body weight in relatives of affected
      probands. Further insight into pathogenetic mechanisms underlying anorexia
      nervosa might be gained by contrasting the epidemiological, psychopathological
      and prognostic factors with those in severe obesity. Thus, epidemiological
      studies suggest that females are more likely to develop both extreme underweight
      and extreme obesity. A possible explanation for this phenomenon is that the, on
      average, higher percentage of total body weight composed of fat mass might
      predispose females towards the development of both extreme weight conditions.

PMID- 7814010
TI  - Association between coronary heart disease and the apolipoprotein A-I/C-III/A-IV
      complex in a Japanese population.
AB  - Several studies have reported that a variant allele (S2) of the apolipoprotein
      (apo) A-I/C-III/A-IV complex is associated with hyperlipoproteinemia in some
      populations and that the frequency of this allele is two- to fivefold higher in
      patients with premature coronary heart disease (CHD) than in healthy controls. In
      the present study in a Japanese population, we were unable to confirm the
      association of the S2 allele with either coronary heart disease or elevated serum
      apo C-III levels, as has been previously reported in Caucasians. No genotype
      difference was observed among the severity of coronary heart disease, as
      determined by the number of involved vessels (one, two and three vessel disease),
      compared to controls. In addition, the frequency of the S2 allele among Japanese,
      in both CHD (0.328) and controls  (0.369), was quite different from that in many
      other populations.

PMID- 7814011
TI  - Novel mutation at the initiation codon in the Norrie disease gene in two Japanese
      families.
AB  - We have identified a new mutation of Norrie disease (ND) gene in two Japanese
      males from unrelated families; they showed typical ocular features of ND but no
      mental retardation or hearing impairment. A mutation was found in both patients
      at the initiation codon of exon 2 of the ND gene (ATG to GTG), with otherwise
      normal nucleotide sequences. Their mothers had the normal and mutant types of the
      gene, which was expected for heterozygotes of the disease. The mutation of the
      initiation codon would cause the failure of ND gene expression or a defect in
      translation thereby truncating the amino terminus of ND protein. In view of the
      rarity and marked heterogeneity of mutations in the ND gene, the present
      apparently unrelated Japanese families who have lived in the same area for over
      two centuries presumably share the origin of the mutation.

PMID- 7814012
TI  - Characterization of a splicing mutation in the factor VIII gene at the RNA level.
AB  - Haemophilia A is an X-linked bleeding disorder caused by mutations in the
      coagulation factor VIII (FVIII) gene. The identification and characterization of
      naturally occurring disease-producing mutations allows the recognition of new
      mechanisms of pathogenesis in haemophilia A. Analysis of the illegitimately
      transcribed FVIII mRNA in a severely affected patient has revealed that the A-->G
      transition at position -2 of the acceptor splice site of intron 4 results in the
      skipping of exon 5 in 90% of the processed pre-mRNA. Another minor mRNA species
      arising from the skipping of exons 4 and 5 has also been observed. The skipping
      of exon 5 predicts the removal of the corresponding 13 amino acids from the A1
      domain of FVIII. A novel missense mutation, C329S, in exon 8 of FVIII gene has
      been identified in another patient.

PMID- 7814013
TI  - PKU in Slovakia: mutation screening and haplotype analysis.
AB  - The restriction fragment length polymorphism haplotypes and seven common
      mutations in the phenylalanine hydroxylase gene were analysed in 49 unrelated
      Slovak phenylketonuria (PKU) families of Caucasian origin. The predominant
      mutation in this population sample is R408W, with a frequency of 45.9%. In
      addition, four other mutations have been identified at relatively high
      frequencies: IVS12nt1, 10.2%; R158Q, 7.1%; R261Q, 7.1%; R252W, 2.0%. The mutation
      haplotype associations correspond to those described in other European
      populations. The high proportion of mutations (72.4%) amenable to simple rapid
      detection based on the polymerase chain reaction provides a good basis for direct
      DNA-diagnosis of PKU in the Slovak population.

PMID- 7814014
TI  - Failure to detect Glut4-Ile383 and IR-Gln1152 variants in NIDDM (non-insulin
      dependent diabetes mellitus) and control subjects in an Italian population.
AB  - Insulin receptor (IR) and insulin-responsive glucose transporter (Glut4)
      represent two candidate genes involved in the development of non-insulin
      dependent diabetes mellitus (NIDDM); detection of molecular alterations in these
      genes might explain their possible contribution to NIDDM. Recently, mutations
      within the coding region of IR and Glut4 have identified: they include the
      Glut4Ile383 and IRGln1152 variants which were found at low frequencies in
      diabetic Caucasian populations. In this study Italian NIDDM patients and control
      subjects were analysed and mutated alleles were not found. Therefore in our
      population these variants appear to have little relevance to the genetic
      susceptibility to NIDDM.

PMID- 7814015
TI  - Trisomy 21 and maternal age of menopause: does reproductive age rather than
      chronological age influence risk of nondisjunction?
AB  - The biological basis underlying the increased risk of nondisjunction in offspring
      of women of advanced maternal age is not understood. We sought to test the
      hypothesis that maternal reproductive age (distance in time from approaching
      menopause) rather than chronological age is pivotal in the etiology of
      nondisjunction. Our results found no difference in age of menopause between women
      > or = 30 years old at delivery of a child with trisomy 21 (i.e., age-related
      nondisjunction) compared to controls. Among women < 30 years of age at delivery
      of a child with trisomy 21, none underwent premature menopause. Therefore, our
      findings fail to support the theory that reproductive age plays a major role in
      the etiology of nondisjunction.

PMID- 7814016
TI  - Five new microsatellite polymorphisms at the q21 region of human chromosome 21.
AB  - Five clones, containing polymorphic CA-repeat sequences, have been isolated from
      a specific human chromosome 21 phage library and have been localised to band q21
      of chromosome 21 using a somatic cell hybrid panel. These highly repetitive
      sequences (D21S1263, D21S1264, D21S1415, D21S1417 and D21S1420) have been
      characterised in the CEPH reference parents and have heterozygosities ranging
      from 0.30 to 0.81 and an average polymorphism information content (PIC) of 0.62.
      The relative order of these markers, based on the somatic cell hybrid panel, is
      cen-D21S1417, D21S1420-D21S1263, D21S1415-D21S1264-tel. The most polymorphic
      marker (D21S1264) has been included in the chromosome 21 genetic map. They have
      also been localised in the CEPH/Genethon YAC panel, providing a refined
      localisation of these polymorphic sequences. These five CA-repeat markers should
      provide a better characterisation of the q21 region of chromosome 21.

PMID- 7814017
TI  - Use of the primed in situ labelling (PRINS) technique for a rapid detection of
      chromosomes 13, 16, 18, 21, X and Y.
AB  - The primed in situ labelling (PRINS) technique is an alternative to in situ
      hybridization for chromosomal screening. We have developed a semi-automatic PRINS
      protocol, using a programmable thermocycler. The method has been successfully
      tested with specific primers for chromosomes, 13, 16, 18, 21, X and Y. Specific
      chromosome detection has been obtained on both metaphases and interphase nuclei.
      This suggests that PRINS may be a reliable technique for detecting aneuploidies
      and some chromosomal aberrations.

PMID- 7814018
TI  - A point mutation in the tyrosine hydroxylase gene associated with Segawa's
      syndrome.
AB  - We have examined the molecular basis of Segawa's syndrome in six families with
      seven affected children. In one family two siblings with this disease carried a
      point mutation in exon 11 of the tyrosine hydroxylase gene, resulting in an amino
      acid exchange of Gln381 to Lys381. These results suggest that a change in
      tyrosine hydroxylase causes this form of Segawa's syndrome.

PMID- 7814020
TI  - ANT3 and STS are autosomal in prosimian lemurs: implications for the evolution of
      the pseudoautosomal region.
AB  - Comparative in situ hybridization in various primate species has revealed a
      pseudoautosomal location for the human ANT3 gene and an X-specific location for
      the steroid sulfatase (STS) gene throughout the higher primate species up to the
      New World monkeys. However, ANT3 and STS map together on an autosome of two
      prosimian species of the genus Lemur and Eulemur. These results suggest an
      autosome-to-X/Y translocation after the simians radiated from the prosimians,
      resulting in a pseudoautosomal location of genes such as ANT3 and STS. In simian
      primates, STS then became X-specific by a pericentric inversion in the Y
      chromosome followed by mutational inactivation of the Y allele.

PMID- 7814019
TI  - Positional cloning of cDNAs from the human chromosome 3p21-22 region identifies a
      clustered organization of zinc-finger genes.
AB  - The human 3p21-22 region is frequently involved in karyotype rearrangements
      associated with malignancies. The high frequency of allelic loss in this region
      has been associated with virtually all small cell lung carcinomas and many renal
      carcinomas. These findings suggest that at least one tumor-suppressor gene might
      be located in 3p21-22. We have recently reported the isolation of a 750-kb yeast
      artificial chromosome (YAC) contig from 3p21-22. Here, we describe three new
      genes isolated from the 3p YAC contig by using a cDNA hybridization selection.
      Remarkably, the three new genes encode zinc-finger proteins, indicating the
      presence of a cluster of zinc-finger genes in human chromosome 3p21.

PMID- 7814021
TI  - Multi-PRINS: multiple sequential oligonucleotide primed in situ DNA synthesis
      reactions label specific chromosomes and produce bands.
AB  - A fast method for identifying several chromosomes with chromosome-specific
      oligonucleotide primers directing an in situ labeling reaction is described. Up
      to three reactions distinguished by different fluorochromes (fluorescein
      isothiocyanate, rhodamine/Texas red, p-amino-methyl-cyclohexane carboxylic acid)
      can currently be performed. Prospects for increasing this up to seven colors, and
      for the future of the process in prenatal diagnosis are discussed.

PMID- 7814022
TI  - Evidence for an iduronate-sulfatase pseudogene near the functional Hunter
      syndrome gene in Xq27.3-q28.
AB  - We are currently characterizing mutations of the iduronate-2-sulfatase (IDS) gene
      in patients with Hunter syndrome (mucopolysaccharidosis type II). Surprisingly,
      all 17 patients with a mutation in exon III of the IDS gene identified by us were
      found to carry both the mutant and wild-type sequences in polymerase chain
      reaction (PCR) products amplified from genomic DNA. Similarly, two unaffected
      male controls showed a heterozygous pattern for two different point mutations in
      exon III. Collectively, the data suggest that at least intron 2, exon III, and
      the 3'-half of exon II of the functional IDS gene are present in the human genome
      as (part of) a non-expressed IDS gene. Deletion mapping further suggests that the
      pseudogene is in distal Xq in physical proximity to the functional IDS gene. The
      high degree of sequence homology observed between the functional IDS gene and
      pseudogene results in permanent co-amplification in PCR-based screening methods
      and makes mutation analysis at the genomic DNA level difficult.

PMID- 7814023
TI  - Apolipoprotein E (apoE) polymorphism and its influence on ApoE concentrations in
      the cerebrospinal fluid in Finnish patients with Alzheimer's disease.
AB  - The apoE phenotype of 83 patients with probable Alzheimer's disease (AD) and of
      164 non-demented controls was determined by isoelectric focusing and Western
      blotting. The proportion of the epsilon 4 allele was 0.548 in AD and 0.202 in
      controls (P < 0.0001). The effect was seen in both early-onset and late-onset AD
      patients. The risk of AD in epsilon 4 homozygotes was 18-fold greater than in
      individuals without the epsilon 4 allele. ApoE concentrations were measured in
      serum and cerebrospinal fluid (CSF) from a subgroup of patients with AD (n = 72)
      and controls (n = 84) by a sandwich enzyme-linked immunosorbent assay. Although
      serum apoE concentrations were lower in individuals with the epsilon 4 allele
      than in those without the epsilon 4 allele, CSF apoE concentrations did not vary
      in different phenotype groups. However, CSF apoE levels were lower in AD patients
      than in controls. We conclude that the inheritance of the epsilon 4 allele of
      apoE is a risk factor for AD in the Finnish population.

PMID- 7814024
TI  - Fluorescence in situ hybridisation studies provide evidence for somatic mosaicism
      in de novo dystrophin gene deletions.
AB  - The fluorescence in situ hybridisation (FISH) technique was tested for its
      ability to detect somatic mosaicism in mothers of isolated deletion cases of
      Duchenne/Becker muscular dystrophy. A control female with known germline and
      somatic mosaicism was examined, and both the normal cell line and the carrier
      cell line were detected. Subsequent FISH analysis of three other mothers of boys
      with apparent de novo dystrophin gene deletions revealed a second patient with a
      high level of somatic mosaicism, suggesting that a proportion of de novo
      dystrophin gene deletions occur as mitotic errors early in development rather
      than as meiotic errors during gametogenesis.

PMID- 7814025
TI  - High frequency of the apo epsilon 4 allele in Khoi San from South Africa.
AB  - Variation at the apolipoprotein E (apo E) gene locus affects cholesterol
      concentrations, the risk for atherosclerosis and Alzheimer disease (AD), and is
      associated with longevity in Caucasians. We have determined apo E gene
      frequencies and effects on cholesterol levels in Khoi San (Bushmen) from South
      Africa. The frequency of the apo epsilon 4 allele (0.37), which confers dose
      dependent susceptibility to atherosclerosis and AD in Caucasians, was twice as
      high, and apo E4 homozygotes were 3-5 fold more frequent in the Khoi San
      (approximately 10%) compared with Caucasians (2%-3%). No significant effect of
      apo E variation on cholesterol concentration was noted in this non-Westernized
      population with low plasma cholesterol (mean cholesterol 149 mg/dl). This
      suggests that Bushmen carry a heavy genetic burden for these late-onset disorders
      if exposed to a Western lifestyle.

PMID- 7814026
TI  - High resolution mid-prophase human chromosomes induced by echinomycin and
      ethidium bromide.
AB  - The antitumor antibiotic echinomycin (EM) was used in combination with ethidium
      bromide (EB) to induce high resolution mid-prophase chromosomes from amethopterin
      synchronized blood lymphocytes. With this combination of drugs, trypsin G-banded
      chromosomes showed over 1200 bands per haploid set in cells having a mid-prophase
      length of decondensation.

PMID- 7814027
TI  - Fine mapping of a putatively imprinted gene for familial non-chromaffin
      paragangliomas to chromosome 11q13.1: evidence for genetic heterogeneity.
AB  - Autosomal, dominantly inherited, non-chromaffin paragangliomas are tumors of the
      head and neck region occurring with a frequency of 1:30,000. Genomic imprinting
      probably influences the expression of the disorder, because tumor development is
      limited to individuals who have inherited the trait from their father. By linkage
      analysis and haplotyping of a single large family in which the pattern of
      inheritance is consistent with genomic imprinting, we have mapped the gene to a 5
      cM region of chromosome 11q13.1 between D11S956 and PYGM. A maximum lod score of
      7.62 at theta = 0.0 was obtained for D11S480. This interval does not overlap with
      a recently assigned locus for glomus tumors in other families: 11q22.3-q23.3.
      Furthermore, analysis of a second family showing the imprinting phenomenon
      resulted in the exclusion of the 5 cM area as the location of the disease gene,
      whereas an indication for linkage was obtained (Z = +2.65) with markers from the
      distal locus. These observations argue for the presence of two distinct imprinted
      genes for glomus tumors on 11q. A model for tumor initiation and progression is
      presented based on all available information.

PMID- 7814029
TI  - Linkage analysis in a Dutch family with X-linked recessive congenital stationary
      night blindness (XL-CSNB).
AB  - Linkage analysis has been performed in a large Dutch pedigree with X-linked
      recessive congenital stationary night blindness (CSNB) by utilizing 16 DNA
      markers from the proximal short arm of the human X chromosome (Xp21.1-11.2).
      Thirteen polymorphic markers are at least partially informative and have enabled
      pairwise and multipoint linkage analysis. For three loci, i.e. DXS228, the
      monoamine oxidase B gene and the Norrie disease gene (NDG), multipoint linkage
      studies have yielded maximum lod scores of > 3.0 at a recombination fraction of
      zero. Analysis of recombination events has enabled us to rule out the possibility
      that the underlying defect in this family is allelic to RP3; the gene defect
      could also be excluded from the proximal part of the region known to carry RP2.
      Linkage data are consistent with a possible involvement of the NDG but mutations
      in the open reading frame of this gene have not been found.

PMID- 7814028
TI  - XY gonadal dysgenesis and gonadoblastoma: a study in two sisters with a cryptic
      deletion of the Y chromosome involving the SRY gene.
AB  - This paper reports a case of XY gonadal dysgenesis in two sisters. Both patients
      presented an eunochoid female phenotype with normal external genitalia. At
      laparotomy, the elder sister was found to have bilateral gonadoblastoma.
      Cytogenetic studies, which included G and C banding and in situ hybridization,
      showed that the patients had an apparently normal 46, XY karyotype. PCR analyses
      revealed absence of the conserved portion (HMG box) of the SRY gene and of the Y
      chromosome pseudoautosomal boundary region sequence in both patients. The
      presence of the ZFY sequence was detected by Southern hybridization in the two
      affected sisters. The patients' father (46, XY, no mosaicism detected in
      peripheral blood lymphocytes) was positive for SRY and ZFY sequences. The
      occurrence of gonadoblastoma is discussed in terms of the genetic factors that
      may lead to tumor development.

PMID- 7814030
TI  - Evidence for a major gene (RP10) for autosomal dominant retinitis pigmentosa on
      chromosome 7q: linkage mapping in a second, unrelated family.
AB  - Retinitis pigmentosa is a genetically heterogeneous form of retinal degeneration,
      which has X-linked, autosomal recessive and autosomal dominant forms. The disease
      genes in families with autosomal dominant retinitis pigmentosa (adRP) have been
      linked to six loci, on 3q, 6p, 7p, 7q, 8q and 19q. In a large American family
      with late-onset adRP, microsatellite markers were used to test for linkage to the
      loci on 3q, 6p, 7p, and 8q. Linkage was found to 7q using the marker D7S480.
      Additional microsatellite markers from 7q were then tested. In total, five
      markers, D7S480, D7S514, D7S633, D7S650 and D7S677, show statistically
      significant evidence for linkage in this family, with a maximum two-point lod
      score of 5.3 at 0% recombination from D7S514. These results confirm an earlier
      report of linkage to an adRP locus (RP10) in an unrelated family of Spanish
      origin and indicate that RP10 may be a significant gene for inherited retinal
      degeneration. In addition, we used recently reported microsatellite markers from
      7q to refine the linkage map of the RP10 locus.

PMID- 7814031
TI  - A topoisomerase II cleavage site is associated with a novel mitochondrial DNA
      deletion.
AB  - Mitochondrial myopathies and encephalopathies can be caused by nucleotide
      substitutions, deletions or duplications of the mitochondrial DNA (mtDNA). In one
      such disorder, Kearns-Sayre Syndrome (KSS), large-scale heteroplasmic mtDNA
      deletions are often found. We describe a 14-year-old boy with clinical features
      of KSS, plus some additional features. Analysis of the entire mitochondrial
      genome by the polymerase chain reaction and Southern blotting revealed a 7864-bp
      mtDNA deletion, heteroplasmic in its tissue distribution. DNA sequencing
      established that the deletion was between nucleotides 6238 and 14,103, and
      flanked by a 4-bp (TCCT) direct repeat sequence. Deletions between direct repeats
      have been hypothesised to occur by a slipped-mismatching or illegitimate
      recombination event, or following the DNA cleavage action of topoisomerase II.
      Analysis of the gene sequence in the region surrounding the mtDNA deletion
      breakpoint in this patient revealed the presence of putative vertebrate
      topoisomerase II sites. We suggest that direct repeat sequences, together with
      putative topoisomerase II sites, may predispose certain regions of the
      mitochondrial genome to deletions.

PMID- 7814032
TI  - Isolation and characterization of a cosmid contig for the GCPS gene region.
AB  - The zinc finger gene GLI3 has been shown to be involved in the embryonal
      development of the limbs and skull. Mutations in GLI3 lead to the development of
      the human Greig cephalopolysyndactyly syndrome (GCPS) and the mouse mutations
      extra toes (Xt) and anterior digit deformity (add). The GCPS locus on human
      chromosome 7p13 has recently been isolated in a yeast artificial chromosome (YAC)
      contig. Here, we describe the establishment of a cosmid contig that was derived
      from two of the YAC clones, that spans 550 kb of human DNA, and that includes the
      GLI3 gene. In this contig, three GCPS translocation breakpoints have been mapped
      to distinct EcoRI fragments in the 3' half of the gene. In addition, exon
      carrying fragments have been identified and the size of the GLI3 gene could be
      determined as at least 280 kb. The gene is flanked by a CpG island that lies on
      the 5' side and that is in close proximity to the first exon detected by the
      cloned GLI3 cDNA. Further upstream, five segments were found that have been
      conserved between man and mouse. In the mouse, this region has been characterized
      as the transgene integration site resulting in the add phenotype. Both the CpG
      island and the conserved regions are probable candidates for a search for GLI3
      promoter and control elements.

PMID- 7814033
TI  - Molecular analysis of the expression of transthyretin in intestine and liver from
      trisomy 18 fetuses.
AB  - Human trisomy 18 (Edwards syndrome) provides a model for the role that genes on
      chromosome 18 play in fetal development. Trisomy 18 occurs in approximately 1 in
      3000 live births. Despite its compatibility with life in 5% of cases, prolonged
      survival is rare. Anomalies involve the urogenital, cardiac, craniofacial and
      central nervous systems. The abnormalities could be caused by the abnormal
      expression of developmentally important genes on chromosome 18. We have
      investigated the quantity and localisation of the expression of a candidate gene,
      transthyretin (TTR), on chromosome 18 at the RNA level in intestine and liver
      tissues from trisomic fetuses and have compared the expression with normal age
      matched fetal tissues. The mRNA level of TTR in 10 to 14-week intestine was the
      same in trisomy 18 and control tissues. However, overexpression was seen for both
      trisomy 18 liver and intestine at 20-23 weeks. TTR transports both thyroxine and
      retinol and is therefore important for normal fetal development.

PMID- 7814034
TI  - Assignment of the developmentally regulated gene NEDD1 to human chromosome 12q22
      by fluorescence in situ hybridization.
AB  - The developmentally regulated mouse gene Nedd 1 encodes a protein showing
      similarities with the beta-subunit of heterotrimeric GTP-binding proteins and has
      growth suppressing activity when overexpressed in various cultured cell types. We
      have mapped the human homolog (NEDD1) of the mouse gene to chromosome 12q22 by
      fluorescence in situ hybridization using R-banded human (pro)metaphase
      chromosomes.

PMID- 7814035
TI  - The human interleukin-10 receptor gene maps to chromosome 11q23.3.
AB  - The human interleukin-10 receptor (IL-10R) gene has previously been mapped to
      chromosome 11. Here, we have determined the precise location of the human IL-10R
      gene by the fluorescence in situ hybridization method, and have found that the IL
      10R gene maps to chromosome 11q23.3.

PMID- 7814036
TI  - Angiotensin II binding to human embryonic lung fibroblasts causes transient
      changes in cytosolic calcium and promotes fibrin gel contraction.
AB  - Contraction of granulation tissue is promoted by the peptide vasoconstrictor
      angiotensin II (AII), which presumably acts on the fibroblasts present in
      granulation tissue. Direct effects of AII on fibroblast contraction were examined
      using an in vitro fibrin gel contraction model. Fibrin gels were formed by mixing
      cultured human embryonic lung fibroblasts with fibrinogen, in the presence of
      thrombin and measurement of gel volume was used to determine the extent of fibrin
      gel contraction by fibroblasts. AII stimulated an additional 28.5 +/- 3% decrease
      in gel size after 24 hr, AII is also shown to specifically bind to human
      embryonic lung fibroblasts and stimulate rapid transient increases in cytosolic
      calcium. AII stimulates contraction of human embryonic lung fibroblasts as
      reflected by acceleration of fibrin gel contraction. Fibrin clot contraction
      contributes to extra cellular matrix reorganization during initial stages of
      wound repair and AII-stimulated fibroblast contraction may accelerate this
      process.

PMID- 7814037
TI  - Ultrastructural cell surface alterations in developing embryos of frog (Microhyla
      ornata) treated with cytochalasins.
AB  - Scanning electron microscopic examination of M. ornata embryos treated with
      cytochalasins A, B and H (CA, CB and CH) showed extensive cell disaggregation
      resulting in large intercellular spaces and apparent loss of intercellular
      communication. All the three cytochalasins significantly reduced surface
      features, such as, filopodia and membrane ruffling which are considered essential
      for normal morphogenetic movements. Appreciable qualitative differences could not
      be detected in effects exerted by CA, CB and CH although potency of the three
      drugs clearly differed. The results demonstrate that in spite of the differences
      in their primary mechanisms of action, treatment with all the three cytochalasins
      culminates in comparable effects on the cell surface architecture resulting into
      abnormal morphogenesis.

PMID- 7814038
TI  - Inhibition of brush border sucrase by indoline 2,3-dione (isatin) in rat small
      intestine.
AB  - Isatin (15-25 mM) inhibited rat brush border sucrase by 40% in presence of Na+
      and the inhibition was enhanced to over 60% in sodium free medium. Sucrase
      inhibition by isatin was dependent on pH. Kinetic analysis revealed a pure
      capacity type (Vmax-effect) inhibition of sucrase activity by isatin in presence
      of sodium. But it changed to affinity type (K-effect) in sodium free medium. The
      value of Ki was around 20-25 mM under these conditions. Enzyme inhibition by
      isatin was alleviated by increasing Na+ or sucrose concentrations. Other
      monovalent cations like K+, Li+ and Cs+ were also effective in restoring the
      enzyme activity to control levels. The effectiveness of the metal ions in
      alleviating the enzyme inhibition was in the order of Na+ > Cs+ > K+ > Li+.

PMID- 7814039
TI  - Dorsolateral prostatic phosphomonoesterases and adenosine triphosphatases in hypo
      and hyperthyroid rats.
AB  - Specific activities of phosphomonoesterases (acid and alkaline phosphatases) and
      adenosine triphosphatases (Mg2+, Ca2+ and Na+/K+ dependent ATPases) of
      dorsolateral prostate were studied in albino rats, under altered thyroid hormone
      status. Thyroidectomy induced hypothyroidism and thyroxine administered
      hyperthyroidism (25 micrograms/100 g body wt/day for 60 days, im) showed no
      impact on the activity of acid phosphatase. Three fold decrease in the activity
      of alkaline phosphatase was observed in hyperthyroid group. Ca2+ and Mg2+
      dependent ATPases were significantly decreased in hypo- and hyperthyroid status
      whereas Na+/K+ ATPase was decreased in hyperthyroidism and showed an opposite
      trend in hypothyroid group.

PMID- 7814040
TI  - Plasmid-determined degradative metabolism and halophilism of Vibrio
      parahaemolyticus.
AB  - A set of 25 Kanagawa(+) and Kanagawa(-) strains of V. parahaemolyticus was
      studied for their ability to degrade hydrocarbons in minimal media. All strains
      gave positive results with respect to crystal violet (CV), methyl violet, liquid
      paraffin, benzene, naphthalene and phenol. The CV double ring (CVDR) response had
      earlier appeared to be a significant pathogenic marker [Chakrabarti et al, Indian
      J Med Res, 85 (1987) 508]. The CVDR response was found also to be a
      biodegradative marker, and correlates perfectly well with polymyxin resistance
      and low level of halophilism (4% NaCl). All these markers (characters) were found
      to be controlled by a single plasmid in the wild type. Elimination of the
      plasmid, as confirmed by gel electrophoresis studies, resulted in loss of CVDR
      response, polymyxin resistance, and acquisition of halophilism at a higher level
      (> 7%). The massive drainage of industrial effluents, rich in hydrocarbons, in
      the estuarine areas in many countries might have altered the ecosystem in favour
      of V. parahaemolyticus and its emergence as a new biodegradative and
      enterotoxigenic pathogen, contaminating fauna and flora in the littoral sea
      regions, with increased changes of communicability to humans.

PMID- 7814041
TI  - Effect of felodipine on myocardial function and cholinergic responses in short
      term streptozotocin diabetes in rats.
AB  - Cardiovascular complications of diabetes mellitus account for 80% of deaths among
      diabetics. Autonomic neuropathy increases the susceptibility of the diabetic
      myocardium to arrhythmias. Decreased contractility of diabetic myocardium is
      associated with intracellular calcium overload. However, the relationship between
      calcium levels and myocardial cholinergic responses is not known. This study was
      undertaken to observe the effect of felodipine 5 mg/kg on myocardial function and
      cholinergic responses of the spontaneously working isolated heart of rats with
      short term streptozotocin-diabetes. Felodipine was administered (po) for 4 week
      to rats with streptozotocin-diabetes of 4 week duration. Felodipine did not alter
      the blood glucose levels. The increased cardio-somatic ratio in diabetic rats was
      attenuated by felodipine. Diabetic status was associated with decreased coronary
      flow and felodipine increased coronary flow in diabetic rat hearts both before
      and after ACh. It may be concluded that felodipine favourably altered the adverse
      myocardial pathology in experimental diabetes, and this strengthens its use as an
      antihypertensive in diabetics.

PMID- 7814042
TI  - Antiinflammatory effects of an Ayurvedic preparation, Brahmi Rasayan, in rodents.
AB  - Brahmi Rasayan, an Ayurvedic preparation, was studied in rodents for its
      antiinflammatory effects at po doses ranging between 1 and 10 g/kg. The drug
      suppressed various experimentally induced inflammatory reactions and did not show
      any gastric irritation in antiinflammatory doses. It is suggested that it may
      partially mediate its antiinflammatory activity by interfering with the action
      and/or synthesis of prostaglandins and also perhaps by stabilization of the
      lysosomal membranes. Its antiinflammatory activity is comparable to that of
      indomethacin.

PMID- 7814043
TI  - Differential modification of radiation damage in 5-bromo-2-deoxy-uridine
      sensitized human glioma cells and PHA-stimulated peripheral leukocytes by 2-deoxy
      D-glucose.
AB  - Effects of 5-bromo-2-deoxy-uridine (BrdU) and 2-deoxy-D-glucose (2-DG) on 60-Co
      gamma-ray induced damage were studied in monolayer cultures of glioma (BMG-1)
      cells, and PHA-stimulated peripheral leukocytes from normal donors. Micronuclei
      formation was used as an index of cytogenetic damage. BrdU and 2-DG treatments
      did not induce micronuclei formation in unirradiated cultures. Presence of BrdU
      (0.8 microM) for more than one cell cycle (24 hr) significantly increased gamma
      ray (1-4 Gy) induced micronuclei formation in exponentially growing BMG-1 cells.
      Incubation of irradiated cells under sub-optimal growth conditions (DMEM with 1%
      serum) for 3 hr, instead of growth medium, significantly decreased micronuclei
      formation. Post-irradiation presence of 2-DG (5 mM; 3 hr, in DMEM + 1% serum)
      significantly increased radiation damage. In BrdU sensitized cells also, 2-DG
      significantly increased radiation damage further. In PHA-stimulated leukocytes
      from normal donors, 2-DG (5mM, equimolar with glucose; for 2 hr) did not increase
      gamma-ray (2-Gy, 42 hr after PHA-stimulation) induced micronuclei formation. Pre
      irradiation presence of BrdU (1.6 microM) significantly increased micronuclei. On
      the contrary, 2-DG treatment reduced radiation induced micronuclei formation in
      BrdU sensitized leukocyte cultures. These results suggest that (i) radiation
      induced lesions leading to micronuclei formation in proliferating tumour cells,
      are, at least, partly repairable; (ii) combination of 2-DG could reduce BrdU
      doses required for radiosensitization of proliferating tumour cells; and (iii) 2
      DG could differentially increase radiation damage in BrdU sensitized
      proliferating tumour cells, while reducing manifestation of damage in normal
      proliferating cells.

PMID- 7814044
TI  - Chemopreventive action of Liv. 52 on DMBA-induced papillomagenesis in skin of
      mice.
AB  - DMBA (195 nmol/50 microliters of acetone/animal) was applied topically over the
      dorsal skin of the mice and tumors were promoted by repeated applications of
      croton oil (1% in acetone, three times per week) after two weeks of DMBA
      application. Skin papillomas appeared in 100% animals in control as well as in
      groups treated orally with Liv. 52 at post-initiational stages and continuously
      at peri-initiational and post-initiational stages of papillomagenesis. When Liv.
      52 was given orally at the peri-initiational stage of papillomagenesis, the
      percentage of mice bearing tumors was 75% and the tumor mean per mouse was
      reduced to 4.0 +/- 1.63 as compared to 7.5 +/- 3.54 in the control group after 15
      weeks of observation. The tumor mean per mouse was observed to be 4.75 +/- 0.55
      and 2.5 +/- 0.57 in the groups treated orally with Liv. 52 at the post
      initiational stages and continuously at peri-initiational and post-initiational
      stages of papillomagenesis respectively. Similarly, the cumulative number of
      papillomas after 15 weeks was 30 in the control group, which was reduced to 10 in
      the animals treated with Liv. 52 continuously at peri-initiational and post
      initiational stages. The cumulative number of papillomas was also reduced to 16
      and 19 in animals treated with Liv. 52 at peri-initiational and post-initiational
      stages, respectively.

PMID- 7814045
TI  - Fat and oil inhibit phosphine release from aluminium phosphide--its clinical
      implication.
AB  - Poisoning by suicidal or accidental ingestion of aluminium phosphide (AlP) is a
      frequent medical emergency seen all over the world. AlP, a grain fumigant and
      rodenticide, on exposure to moisture, liberates highly toxic gas, phosphine. The
      rapidly inhibits mitochondrial respiration and has cytotoxic action. No specific
      antidote is known against it till date and prognosis depends much on dose and
      time lag between AlP ingestion and the stomach wash in the hospital (critical
      period). Physicochemical properties of AlP and nonmiscibility of fat and water
      promoted us to study the effect of different fats and oils as possible antidotes
      to inhibit phosphine liberation. In vitro experiments revealed that vegetable
      oils and liquid paraffin were much more effective than butter and ghee in
      inhibiting release of phosphine from AlP. These findings may have significant
      clinical implication.

PMID- 7814046
TI  - Anoxic changes in cerebral cortex of albino rats following experimental carotid
      occlusion.
AB  - Neuronal and glial changes following experimental cerebral ischaemia showed
      neuronal shrinkage and astrocytic proliferation after temporary bilateral
      clamping of carotid arteries, and extensive neuronal damage with areas of
      haemorrhage following bilateral carotid ligations in rats.

PMID- 7814047
TI  - Relative efficacy of egg albumin as blocking agent in dot immunobinding assay for
      detection of group B coxsackieviruses.
AB  - Non specific binding (NSB) is an important factor affecting sensitivity and
      specificity in dot immunobinding assay (DIA). Several blocking agents e.g. egg
      albumin, casein, gelatin, milk powder and goat serum were evaluated for their
      relative efficacy vis-a-vis bovine serum albumin (BSA) for DIA system purported
      for detection of group B coxsackieviruses (CVB). The results suggest that egg
      albumin (5%) which is economical and readily available may act as an effective
      blocking agent in DIA system.

PMID- 7814048
TI  - A device for monitoring and control of mosquitoes by behaviour manipulation.
AB  - A trap was designed and fabricated for capturing mosquito larvae based on their
      behavioural responses to food and light. The larvae upon entering the trap died
      ultimately due to asphyxiation. Maximum success was achieved with Aedes aegypti
      larvae in lesser water volumes. The usefulness of the device for studying the
      response of mosquito larvae and aquatic organisms to chemicals, baits, light,
      various stimuli and possible pest/vector monitoring and management in aquatic eco
      system is discussed.

PMID- 7814049
TI  - Production of ampicillin through Escherichia coli NCIM 2563 immobilized and cross
      linked in alginate beads.
AB  - 6-Amino penicillanic acid (6-APA) was condensed with D-alpha-phenyl glycine
      chloride in presence of E. coli NCIM 2563 to form ampicillin. At pH 5, 30% of 6
      APA was converted to ampicillin during 1 hr incubation. When E. coli cells were
      immobilized in calcium alginate beads, the activity remained unaffected even
      after six batches of bioconversion. Inclusion of glutaraldehyde as
      multifunctional cross-linking agent, improved the stability of the biocatalyst
      beads.

PMID- 7814050
TI  - Hepato protective effect of Liv-52 against CCl4 induced lipid peroxidation in
      liver of rats.
AB  - Effect of oral feeding of Liv-52, on lipid peroxidation in normal liver and
      damaged liver induced by CCl4 of albino rats was studied. While Liv-52 did not
      show any effect on normal healthy liver cells, it had a significant protective
      effect against damage by CCl4 as shown by significant decrease in
      malonaldialdehyde content.

PMID- 7814051
TI  - Bypassing successive cloning of two fragments by one step cloning using
      polymerase chain reaction.
AB  - The polymerase chain reaction (PCR) was used for bringing together two DNA
      fragments present in two different plasmids. This helped avoiding the
      difficulties of two successive subcloning in the same plasmid and uncertainities
      of obtaining rightly oriented constructs. Two different fragments of DNA present
      in different plasmid were digested with the same enzyme and then ligated. The
      ligation mixture was used for the PCR using two oligo primers; one was specific
      for the 5' end of the other fragment and the other one was for the 3' end of the
      other fragment. The desired amplified fragment was separated by gel
      electrophoresis, eluted and was cloned in plasmid pBluescript KS(+). The same
      procedure is also applicable for one step cloning of more than two fragments in
      desired orientation.

PMID- 7814053
TI  - Confidence in fine needle aspiration cytology.

PMID- 7814052
TI  - Correlation of metal distribution, reduced glutathione and metallothionein levels
      in liver and kidney of rat.
AB  - Effect of group IIB metals on the endogenous status of metallothionein (MT) and
      reduced glutathione (GSH) was studied in two vital detoxifying organs namely,
      liver and kidney of rat. The metals were administered at non lethal levels (1/10
      LD50) which were found to cause no death. Zinc showed accumulation in both liver
      and kidney, cadmium preferentially in the liver while mercury in the kidney.
      Hepatic MT content was increased by 18-fold, 15-fold and 2-fold by cadmium, zinc
      and mercury respectively while renal MT was increased maximally by zinc. Among
      the metals, mercury caused highest depletion of hepatic GSH level (51%). The
      renal GSH showed differential response to the metal treatment, the level
      increasing slightly by cadmium and depleting significantly by zinc and mercury. A
      positive correlation was found between group IIB metal accumulation and the
      manifestation of toxic response.

PMID- 7814054
TI  - Fine needle aspiration cytology (FNAC) in malignant bone tumours.
AB  - Patients with malignant bone tumours often come at a very late stage of disease
      to Medical Colleges. Because of their high mortality rate, accurate & quick
      diagnosis of these lesions become essential, inspite of clinical, radiological
      and histopathological assessments. A simple, inexpensive, safe & least traumatic
      technique-fine needle aspiration cytology (FNAC) in diagnosis of 55 malignant
      bone tumours was carried out. Specific tumour types metastatic tumour (12), Giant
      cell tumour (12), Ewing's sarcoma (10), Osteosarcoma (7), Multiple myeloma (7),
      Chordoma (3), Chondrosarcoma (3) and Fibrosarcoma (1) could be ascertained in
      87.2% whereas malignant tumour was suggested in 94.5% (52 cases).

PMID- 7814055
TI  - CT-guided needle aspiration cytology (FNAC) of 112 vertebral lesions.
AB  - Aspiration cytology under CT-guidance was utilised as a diagnostic device in 112
      lesions of vertebrae from January, 1985 till August, 1992. The age of the
      patients ranged from 6 years to 82 years. The materials were spread on glass
      slides, air-dried and stained by May-Grunwald and Giemsa method. In few cases
      part of the aspirated material was utilised for special stain and cell block
      preparation. Analysis of results showed metastatic tumours in 61 cases,
      Tuberculous lesions in 24 cases, Plasmacytoma in 6 cases, Giant cell lesion in 6
      cases, Eosinophilic Granuloma in 3 cases, Chordoma in 3 cases, Ewing's sarcoma in
      2 cases, Hodgkin's disease in 2 cases, Chondrosarcoma in 1 case and no definite
      diagnosis was given in 4 cases. These 4 cases on exploration and biopsy proved to
      be osteoblastoma (2), haemangioma (1) and undifferentiated sarcoma in the other.
      The giant cell lesions on histopathology proved to be aneuryamal bone cysts in 4
      cases while osteoclastoma in 2 cases. The diagnostic accuracy was 96.4%. No
      complication was encountered in the present study. Early diagnosis by needle
      aspiration cytology (NAC) prevented unnecessary surgical exploration in majority
      of the cases and treatment could be started at the earliest.

PMID- 7814056
TI  - Diagnosis of malignant neoplasms of male breast by fine needle aspiration
      cytology.
AB  - Fine needle aspiration cytology (FNAC) is now an established procedure for the
      evaluation of breast masses in women. But there are only occasional reports of
      aspiration cytology of rare malignant neoplasms of male breast. During the past 8
      years the authors detected 12 malignant neoplasms of male breast by FNAC out of
      total 167 cases of aspirates of male breast lesions. There were eight
      infiltrating ductal carcinomas, two leiomyosarcomas and two metestatic
      carcinomas. The cytologic features with short review of literature of male breast
      carcinomas are presented. Due to high diagnostic accuracy, FNAC should be
      routinely practiced as a quick and safe diagnostic procedure in all outpatients
      department.

PMID- 7814057
TI  - Fine needle aspiration biopsy of pancreas.
AB  - Percutaneous fine needle aspiration biopsy (FNAB) were performed in 22 cases of
      pancreatic lesions. FNAB was done with the help of ultrasonographic guidance in
      14 cases and intraoperatively in 2 cases. In rest of the cases it was done
      without any radiological guidance. Diagnosis was confirmed either by
      histopathology or exploratory laparotomy by follow-up data in rest of the cases.
      There was no false positive or negative diagnosis. Nuclear crowding, nuclear
      enlargement and prominent nucleoli were the important cytological criteria for
      pancreatic adenocarcinoma. Cytology smears of the islet cell tumour show round to
      oval monomorphic cells with central to eccentric nuclei and fine reddish
      granulations in cytoplasm. There was no complication following aspiration. Thus
      FNAB of pancreas is a relatively safe, reliable and quick technique which can be
      performed under ultrasound guidance.

PMID- 7814058
TI  - Transrectal fine needle aspiration cytology of granulomatous prostatitis.
AB  - Transrectal fine needle aspiration cytology by Franzen technique was carried out
      from January, 1985 till January, 1992 on 567 patients having prostatomegaly which
      were suspicious of malignancy by clinical per rectal examination. Granulomatous
      prostatitis was diagnosed in 56 cases. Analysis showed 34 cases were tuberculous
      prostatitis and 22 cases were nonspecific granulomatous prostatitis. Comparison
      of aspiration cytology with bacteriological study of the aspirated material and
      histopathology showed correct diagnosis of granulomatous prostatitis by fine
      needle aspiration. The findings indicate that transrectal fine needle aspiration
      cytology is a reliable procedure for diagnosis of granulomatous prostatitis which
      can clinically mimic prostatic malignancy when it presents as a diffuse or
      nodular enlargement with firm to hard consistency.

PMID- 7814059
TI  - Aspiration cytology of salivary gland lesions advantages and pitfalls.
AB  - FNAC of the major salivary glands was performed on 72 patients during a period of
      two and a half years. In 64 patients samples were satisfactory. The cytologic
      diagnosis was correlated with histology available in 36 cases. 21 out of 22
      benign lesions and 12 out 4 malignant lesions were correctly identified rendering
      a diagnostic accuracy of 91 percent. The pitfalls of FNAC of salivary gland
      lesions are reflected by the overall false positive rate of 5.5 percent of false
      negative rate of 2.7 percent. Diagnostic pitfalls are due to variability of tumor
      morphology which makes sampling & interpretation difficult. Multiple sampling and
      increasing experience help to minimize errors.

PMID- 7814060
TI  - Cholera epidemic in Goa.
AB  - Two hundred and fifty stool samples were studied during an outbreak of cholera in
      Goa during the months of July to September, 1988. 80 strains of Vibrio were
      isolated with an isolation rate of 32%. 72.5% of those affected were adults. All
      strains of Vibrio cholerae isolated belonged to Eltor biotype, Fifty three
      (66.25%) of them being Ogawa serotype while 21 (26.25%) were Inaba. NAG Vibrios
      accounted for 6 (7.5%) strains. Antimicrobial sensitivity pattern showed high
      degree of sensitivity to chloramphenicol, gentamicin and naladixic acid.

PMID- 7814061
TI  - Mycoplasma hominis in pelvic inflammatory disease.
AB  - Fifty one cases of Pelvic Inflammatory disease (PID) and sixty one control
      subjects were screened for the genital mycoplasmas. Cervical swabs, urine & blood
      were collected from the patients and the control subjects and were processed by
      standard techniques for isolation and identification of bacteria, fungi and
      mycoplasmas. The rate of isolation of M. hominis from the PID and controls were
      54.90% and 16.39% respectively, and this difference was statistically significant
      (p. < 0.001). Metabolic inhibition test revealed a titer of > 1:2 in 92% of the
      acute sera of PID against the homologous strain and there was a rise or fall in
      four fold titer in 45% of the convalescent sera tested for.

PMID- 7814062
TI  - Bacteriology of acute appendicitis with special reference to anaerobes.
AB  - Bacterial flora of 105 patients of acute appendicitis of which 101 showed acute
      inflammation and 4 a normal appendix, was studied. A total of 121 anaerobes and
      149 aerobes were isolated with an average of 1.15 anaerobes and 1.41 aerobes per
      specimen. Mixed flora was found in 100 (95.2%) specimens. Bacteroides fragilis
      and Escherichia coli were the most predominant anaerobes and aerobes respectively
      and their combination was most frequently seen. There were no significant
      differences in the rate of isolation of B. fragilis between the perforated/non
      perforated and inflamed/normal appendices. Hundred percent anaerobes were
      sensitive to clindamycin and 93.38% to metronidazole.

PMID- 7814063
TI  - Gaucher's disease among Mappila Muslims of Malabar.
AB  - Seven cases of Gaucher's disease admitted in Medical College, Calicut, Kerala
      State, were studied. All cases were classified as Type I (adult) Gaucher's
      disease. Splenomegaly was the consistent feature. Routine hemogram and liver
      function tests were within normal range. Bone marrow smears and liver biopsies
      were studied. Bone marrow smears showed typical Gaucher cells. In liver biopsy
      storage cells were seen as scattered foci in sinusoids. One case showed diffuse
      distribution affecting all zones. All cases belonged to distinct community called
      Mappila Muslims of Malabar which account for only 35 percent of the population in
      Malabar region, situated in the northern part of Kerala. Type I Gaucher's disease
      has a well known racial predilection reported in Askenazi Jews. Mappila Muslims
      of Malabar may be another such group. This is the largest series of cases to be
      published in India seen in one particular community.

PMID- 7814064
TI  - Sensitivity to the bactericidal effect of normal human serum on Klebsiella
      strains from different sources.
AB  - A total 270 Klebsiella strains isolated from clinical infections, faeces of
      healthy food handlers and environmental sources were studied. Of the strains
      tested 177 (65.6%) were serum sensitivity, 71 (26.3%) were serum resistant and
      the remaining 22 (8.1%) showed intermediate sensitivity to pooled normal human
      serum (PNHS). Faecal coliform (FC) reaction was positive in 59 per cent and 6 per
      cent for K. pneumoniae and K. oxytoca respectively.

PMID- 7814065
TI  - A sequential study of humoral factors in ovarian neoplasms.
AB  - A sequential study of serum immunoglobulins, circulating immune-complexes (CIC)
      and blocking effect of patients' sera on normal T lymphocytes was conducted in 15
      patients with benign ovarian tumour, 32 with carcinoma ovary and 20 agematched
      healthy women. In patients with benign ovarian tumour there was a significant
      increase in IgG and IgM, while IgA was not altered. In carcinoma, there was no
      significant change in IgG and IgM but IgA was found to be increased significantly
      as compared to benign ovarian tumour. Post-operatively, IgM showed a significant
      increase on the 10th day, probably due to the effect of surgery. There was no
      significant difference in CIC levels and percentage T cell depression between
      patients with benign ovarian tumours and healthy controls. In carcinoma ovary
      both these parameters were increased significantly as compared to benign ovarian
      tumours. After tumour ablation, they were decreased significantly, until there
      was recurrence. The alterations in these parameters was not related to any
      specific histologic type of neoplasm. The study of serum immunoglobulins
      indicates tumour load, while the estimation of CIC and blocking effect of cancer
      sera on normal lymphocytes is of a definite diagnostic and prognostic
      significance.

PMID- 7814066
TI  - Unilocular cystic sebaceous lymphadenoma of the parotid gland.
AB  - Unilocular Cystic Sebaceous Lymphadenoma of the parotid gland also described as
      benign lymphoepithelial parotid cyst with sebaceous differentiation is an unusual
      tumour which histogenetically resembles Warthin's tumour. We present two such
      cases reported in the department of Pathology, Kasturba Medical College with
      review of the literature on histogenesis.

PMID- 7814067
TI  - Sex cord tumour with annular tubules--a case report.

PMID- 7814068
TI  - Jejunal diverticulosis--a report of five cases and review of literature.

PMID- 7814069
TI  - Rhinosporidiosis presenting as urethral polyp.
AB  - Rhinosporidiosis is a very common disease endemic in India, Ceylon, East Africa
      and part of America. Extremely rare in Europe. Nose, naso-pharynx, nasal sinuses,
      larynx are the common sites of affection, but urethral lesion is very rare.
      Reports from India so far as our knowledge goes are not available. Symmers may be
      the only case report available so far. For the rarity of site of affection, the
      case is reported.

PMID- 7814070
TI  - Ocular tuberculosis masquerading as retinoblastoma.

PMID- 7814071
TI  - Hydatid cyst of ovary--a case report.
AB  - A rare case of ovarian hydatid cyst has been reported here in a 30 years old
      lady. This lady had a pet dog for last 6 years.

PMID- 7814072
TI  - Pattern of viphage types and emergence of resistance to fluoroquinolones in multi
      drug resistant S. typhi at high altitudes.

PMID- 7814073
TI  - James Lind (1716-1794)

PMID- 7814074
TI  - A role for cytokines in early pregnancy.
AB  - Cytokines are expressed in a variety of cell types of the reproductive system,
      although in most instances their functions are not understood. There are,
      however, a few instances where a role in early pregnancy has been established.
      First, preimplantation conceptuses of ruminant ungulate species, such as cattle,
      sheep and goat, secrete a unique Type I interferon (IFN-tau). By mechanisms that
      are still unclear, IFN-tau prevents the destruction of the corpus luteum and
      hence ensures the continued production of progesterone which is essential for
      continuation of pregnancy. Most like the IFN-tau prevent lutcolysis by modulating
      the output of a luteolytic hormone, prostaglandin F2 alpha, from the uterus.
      Depsite this involvement in pregnancy, the IFN-tau possess similar
      antiproliferative and antiviral activities to other Type I IFN, 1 lambda e.g. IFN
      alpha. There are 4-5 genes for IFN-tau in sheep and cattle whose promotor regions
      are highly conserved and distinct from those of other Type I IFN. These genens
      are not virally inducible and are expressed only in the trophectoderm (outer
      epithelium of the developing placenta) from the time of blastocyst hatching to
      implantation. Leukemia inhibitory factor (LIF) is a multi-functional cytokine
      which is expressed by uterine endometrium of pregnant mice around day 4 of
      pregnancy. Female mice lacking a functional LIF gene are fertile but their
      blastocysts fail to implant, strongly implicating the cytokine in maternal
      control of implantation. Colony stimulating factors (CSF) are a family of
      proteins (GM-CSF, CSF-1, G-CSF, and IL-3) that stimulate the cellular
      proliferation and induction of terminal differentiation of hemopoietic progenitor
      cells. CSF-1 is expressed in the uterine endometrium of the mouse and human
      during early pregnancy and its receptor, fms, is present on trophoblast. The
      osteopetrotic mouse, which represents a natural "knockout" of the CSF-1 gene,
      exhibits a low rate of fetal implantation and poor fetal viability. It seems
      likely that CSF-1 expression by the uterus influences growth and differentiation
      of the placenta. Although different species may utilize different strategies for
      ensuring developmental and endocrinological coordination between the embryo and
      the mother, these three examples illustrate that cytokines are likely to be major
      participants as autocrine factors that direct the events of early pregnancy and
      not simply as modulators of the maternal immune system.

PMID- 7814075
TI  - Effect of carbachol injection in the medial preoptic area on sleep-wakefulness
      and body temperature in free moving rats.
AB  - The aim of the present study was to find out the changes in sleep-wakefulness and
      body temperature brought about by application of cholinergic agonist, carbachol,
      in the medial preoptic area (mPOA). Carbachol, when injected bilaterally into the
      mPOA of male rats, through chronically implanted cannulae, produced a fall in
      rectal temperature and long lasting arousal. There was temporal dissociation in
      the duration of changes produced in the two parameters. It is suggested that the
      cholinergic system at the medial preoptic area brings about arousal response and
      fall in body temperature through different circuits.

PMID- 7814076
TI  - Evidence for catecholamine-depleting action of fluoxetine.
AB  - The present investigation was undertaken to study the interaction of fluoxetine
      with 5-hydroxytryptamine (5-HT) and noradrenaline (NA) in rat anococcygeus muscle
      and vas-deferens. In rat anococcygeus muscle responses to NA were significantly
      potentiated after 30 min and 60 min incubation with fluoxetine (2.9 x 10(-9) M).
      The responses to 5-HT were however, inhibited after 30 min incubation with
      fluoxetine in this preparation. On rat vas-deferens also, the responses to NA
      were potentiated after 30 min incubation with fluoxetine. The response to 5-HT
      were not altered significantly. In rats pretreated with fluoxetine (5 mg/kg, ip)
      for seven days, the responses to NA were significantly potentiated in rat
      anococcygeus muscle. Whereas the responses to 5-HT and tyramine were
      significantly inhibited. The inhibited responses to 5-HT restored back to normal
      when the anococcygeus muscle was pre-incubated with NA for 30 min.

PMID- 7814077
TI  - Some hitherto unreported findings on the extragenital effects of progesterone in
      human females--a clinical study.
AB  - 40 women suffering from 'dysfunctional uterine bleeding' (DUB) were treated by
      progesterone (P) and signs and symptoms of 'extragenital effects' of P were
      noted. In addition to the previous ones reported from this laboratory, a new crop
      of effects, which, as far as we are aware of, have never been reported in the
      literature, were found and included: (i) Changes in the frequency of EEG waves,
      (ii) changes in the ECG (iii) changes in psychoanalytical scoring. Further (iv)
      with most of the parametres, the intensity of the changes showed considerable
      waning with passage time, despite the fact that the subjects were still receiving
      P. Blood P levels similarly fell considerably in the initial phase of the
      therapy, but recovered to some extent afterwards, despite the continuance of P
      therapy.

PMID- 7814078
TI  - Poly ADP ribosylation as a possible mechanism of microwave--biointeraction.
AB  - Electromagnetic fields (EMFs) affect the metabolism of the body including the
      nervous, endocrine, cardiovascular, hematological as well as the reproductive
      system. EMFs are environmental pollutants, thus posing a health hazard which can
      cause steric changes in the molecule located at the cell surface. Microwaves are
      known to cause chromosomal abberations and act as tumor promoters. The process
      involves a stream of signals from cell membrane to nucleus and other organelles.
      The present investigations aim to understand the mechanism of biological effects
      of microwaves (2.45 GHz). The effect was studied on poly ADP-ribosylation, which
      is a post translational modification of chromatin protein catalysed by the enzyme
      poly ADPR polymerase using NAD+ as the substrate. Poly ADP-ribosylation has been
      shown to be involved in several aspects of chromatin structure and function.
      Twenty-three days old rats weighing 42-48 gms were exposed at a microwave dose
      level of 1.0 mW/cm2. After exposure for sixty days the animals were sacrificed
      and an estimation of poly ADPR polymerase activity was undertaken in different
      organs of these animals. There was an increase of 20% in its activity in liver,
      35% in testis, whereas brain showed a 53% decrease in diencephalon and 20%
      decrease in the cortex in the exposed animals as compared to their respective
      controls. There was no change in enzyme activity in spleen and kidney. This was
      accompanied by concomitant changes in NAD+ levels. The above results may be cited
      as important events in carcinogenesis and tumor promotion related to microwave
      exposure and the signal transduction mechanism involved. The goal is to shed
      light on complex ecogenetic interactions leading to cancer modulation of gene
      expression by epigenetic mechanism.

PMID- 7814080
TI  - Histological changes in reptilean spinal cord transection: correlation with
      functional recovery.
AB  - The study of spinal cord regeneration in the phylogenetic scale is likely to help
      us in the understanding of the problem in the human situation. After spinal
      transection in lizards, histological changes in the spinal cord were studied and
      correlated with functional recovery. Some changes in spinal cord, suggestive of
      regeneration between the two stumps were observed. The recovery of function did
      not appear to be dependent on synaptic continuity.

PMID- 7814079
TI  - Control of melanosome movements in isolated skin melanophores of a catfish
      Clarias batrachus (Linn.).
AB  - Adrenergic and cholinergic receptors have been studied in isolated skin
      melanophores of a catfish Clarias batrachus. Catecholamines induced a strong
      aggregatory effect on the melanophores. Melanosome aggregation induced by
      adrenaline and noradrenaline was partially blocked by alpha adrenergic receptor
      blockers and a beta receptor blocker. Cholinomimetic drugs aroused a significant
      dispersion of melanophroes. Atropine effectively blocked the dispersal, responses
      of melanophores to acetylcholine and carbachol, while, hexamethonium blocked the
      nocotine induced dispersal responses of the melanophores.

PMID- 7814081
TI  - Evaluation of PGE2 gel for cervical ripening and induction of labour.
AB  - In a prospective study a single dose PGE2 gel 0.5 mg was given in 97 Low Bishop
      Score subjects, 12 hrs prior to indicated oxytocin or PGE2 tab induction for
      cervical ripening. Analysis of 97 subjects shows that it is very highly
      effective. 56 primi and 21 multi delivered spontaneously with gel administration
      only while 4 primi and 2 multi delivered vaginally following oxytocin and 3 more
      cases delivered vaginally following PGE2 tab administration and fewer caesarian
      section (11) were performed. The endo cervical administration of PGE2 was well
      tolerated and systemic PGE2 effects were minimal.

PMID- 7814082
TI  - Use of antimony (V) arsenosilicate beads for estimation of iron content of
      ayurvedic and allopathic preparations.
AB  - A method has been developed for the standardization of Indian ayurvedic drugs
      containing iron, using inorganic ion exchange material antimony (V)
      arsenosilicate cation exchanger. The iron present in the drug was absorbed
      quantitatively on the columns of the exchanger, eluted with a suitable solvent
      and then titrated against a standardized EDTA solution.

PMID- 7814083
TI  - Histobiochemical changes in lung of protein deficient rats following repeated
      exposures of MIC vapour.
AB  - Adult male albino rats, maintained on normal or protein deficient diets from
      weanling, were exposed to repeated doses of MIC vapour (0.32 mg/L for 8 min for 5
      consecutive days) under static conditions. Histopathology and the activities of
      alkaline and acid phosphatases and GSH content of lung were studied upto day 14
      after exposure. Mild but repeated exposures of MIC vapour caused severe pulmonary
      lesions like denudation of bronchiolar epithelial lining tissue, cellular
      infiltration, edema, emphysema followed by hyperplasia, hypertrophy, fibrosis and
      intraluminal fibroplasia. The activities of alkaline and acid phosphatases were
      increased at earlier intervals while GSH content decreased significantly and
      remained low throughout the experimental duration. Protein deficiency was found
      to aggravate the toxic potentials of MIC in present condition.

PMID- 7814084
TI  - A preliminary audit of practice--antibacterial prophylaxis in general surgery in
      an Indian hospital setting.
AB  - As a major proportion of antibacterials used in hospital practice are for
      surgical prophylaxis, an audit of practice in relation to antibacterial
      prophylaxis in general surgery was undertaken over a four week period in a
      teaching hospital to assess the extent to which principles governing surgical
      antibacterial prophylaxis were practised and to provide a feedback to the
      clinicians. The extent of use of anti-bacterial agents in surgical prophylaxis
      was 90%. The timing of administration was more than 2 h before surgery in 21% of
      the cases. Intravenous route was used in 97% of the cases. The duration of
      prophylaxis was more than 72 h in 48% of cases. Cefazolin was the most frequently
      prescribed either alone or in combination with metronidazole. The study indicated
      inappropriateness in the timing and duration of administration of surgical
      antibacterial prophylaxis.

PMID- 7814085
TI  - Species variation in the specificity of cholinesterases in human and rat blood
      samples.
AB  - Acetylthiocholine iodide (ATC) as a common substrate in the combined assay of red
      blood cell cholinesterase (RBC ChE) and butyrylcholinesterase (BuChE) do not
      provide the accurate individual enzyme activities. Hence, in the present study
      the two enzyme activities in the same sample were assayed with the help of two
      different substrate, ATC and butyrylthiocholine iodide (BTC). Specificity of BTC
      towards BuCHE was found in blood, plasma and serum, while ATC is nonspecifically
      hydrolysed by both RBC ChE and BuChE. ATC gives significantly higher enzyme
      activity (P < 0.001) in rat plasma/serum and significantly lower enzyme activity
      (P < 0.0001; P < 0.001) in human plasma/serum. The possible reasons are discussed
      for substrate specity in various species in the assay of ChEs.

PMID- 7814087
TI  - Effect of thyroxine on taste hedonics in rat.
AB  - 1. The hedonic response to sweetness was tested in 12 thyroxine treated rats
      using the method of single-bottle brief-exposure to sweet (saccharin) solution.
      2. Consumption of the sweet solution was significantly more following
      administration of thyroxine than during the control period. 3. The 1-hr
      consumption of saccharin solution appeared to be more sensitive to thyroxine than
      the 5-minute consumption.

PMID- 7814086
TI  - Correlation of time course of blood cholinesterase activity and toxic
      manifestations of acute methylparathion in antidote treated rats.
AB  - Study was conducted to find out the correlation between red blood cholinesterase
      (RBC ChE) and plasma butyryl cholinesterase (BuChE) activities and toxic signs of
      oral methylparathion (MPT) and their recovery pattern with or without atropine
      treatment in female rats. Enzyme activity was estimated before and after an oral
      dose of MPT (7.5 mg/kg-1) at various time intervals upto 120 hr. Antidote groups
      received atropine (10 mg/kg-1, i.p.), either alone or with diazepam (2.5 mg/kg-1,
      i.p.), at the onset of toxic signs. Inhibition of enzyme activity served as
      definite index of acute toxicity of MPT. RBC ChE activity correlated with the
      intensity of toxic signs in no-antidote rats, while in atropine treated groups,
      there was no correlation. BuChE levels did not correlate with toxic signs in any
      of the groups except in the fatal group. The resynthesis of both the enzymes was
      complete in 120 hr study and did not synchronize with the recovery pattern of
      animals from toxic signs. Compared to BuChE, RBC ChE activity was found to be a
      more sensitive indicator for the diagnosis of severity of MPT toxicity.

PMID- 7814088
TI  - Hypoglycemic effects of leucodelphinidin derivative isolated from Ficus
      bengalensis (Linn).
AB  - A Leucodelphinidin derivative isolated from the bark of Ficus bengalensis Linn
      demonstrated hypoglycemic action at a dosage of 250 mg/kg given both in normal
      and alloxan diabetic rats. It's action is closely similar to that of an effective
      dose of glibenclamide (2 mg/kg) tested under the same conditions. However, after
      a glucose load the plant product is only just significantly active but not as
      effective as the sulphonylurea. The efficacy of the plant product as a
      hydroglycemic agent adds to its other therapeutic effects, as it belongs to the
      class of flavonoids.

PMID- 7814090
TI  - An inexpensive method for fabrication of intracerebroventricular cannulae for
      rats.
AB  - An inexpensive and simple method to fabricate intracerebroventricular (i.c.v.)
      cannulae for rats with readily available material is described here. The
      procedure is cost effective and quick. The cannulae thus designed are suitable
      for injecting minute quantities (microliters) of drugs/chemicals
      interacerebroventricularly for acute or chronic experiments in rats.

PMID- 7814089
TI  - Pharmacological effects of Azadirachta indica (neem) leaf extract on the ECG and
      blood pressure of rat.
AB  - Neem leaf alcoholic extract (NLE) was investigated for its effects on the ECG and
      blood pressure of rat. Intravenous administration of NLE (100, 300 and 1000
      mg/kg) resulted in initial bradycardia followed by cardiac arrhythmia in rats.
      NLE produced a significant and dose-related fall in blood pressure which was
      immediate, sharp and persistent. Pre-treatment with either atropine or mepyramine
      failed to prevent the hypotensive effect of NLE.

PMID- 7814091
TI  - A comparative study of visual and auditory reaction times in males and females.
AB  - Visual and auditory reaction times (VRT and ART) were studied in 38 male and 41
      female healthy medical students in the age group of 17-18 years. Subjects were
      presented with two visual stimuli viz red and green light stimuli and two
      auditory stimuli viz high pitch and low pitch sound stimuli. The R.T. to red
      light was significantly lower than to green light stimulus in both sexes. No
      statistically significant difference was observed in the response to high and low
      pitch sound stimuli in both sexes.

PMID- 7814092
TI  - Respiratory and other hazards of isocyanates.
AB  - Isocyanates are increasingly being used for manufacturing polyurethane foam,
      elastomers, adhesives, paints, coatings, insecticides, and many other products.
      At present, they are regarded as one of the main causes of occupational asthma.
      The large number of workers who are exposed to these chemicals have a
      concentration-dependent risk of developing chronic airway disorders, especially
      bronchial asthma. Different pathophysiologic mechanisms are involved.
      Immunoglobulin E (IgE)-mediated sensitization and irritative effects have been
      clearly demonstrated in both exposed subjects and animals. Presumably, neural
      inflammation due to neuropeptide release of capsaicin-sensitive afferent nerves
      is crucial. We collected data on 1780 isocyanate workers who had been examined by
      our groups. Of them 1095 (including subjects from outpatient departments) had
      work-related symptoms, predominantly of the respiratory tract. Specific IgE
      antibodies were found in 14% of the 1095 subjects. The methacholine challenge
      test was shown to be an inadequate predictor of the results of inhalative
      isocyanate provocation tests in workers and in asthmatic controls. Isocyanate
      (toluene diisocyanate TDI) air concentrations of 10 ppb (0.07 mg/m3) and 20 ppb
      (0.14 mg/m3), respectively, did not cause significant bronchial obstruction in
      the majority of previously unexposed asthmatics with bronchial hyperreactivity.
      IgG-mediated allergic alveolitis, a rare disease among isocyanate workers, was
      found in approximately 1% of the symptomatic subjects. Experimental studies
      exhibit dose-dependent toxic effects and give evidence for tachykinin-mediated
      bronchial hyperreactivity after exposure to isocyanates. The clinical role of
      genotoxic effects of isocyanates and their by-products demonstrated here in vitro
      and in vivo has yet to be clarified.

PMID- 7814094
TI  - Hepatotoxic effects of solvent exposure around permissible limits and alcohol
      consumption in printers over a 4-year period.
AB  - Two field studies were carried out in 1987 and 1991 in order to evaluate the
      effect of chronic exposure to solvent mixture on liver enzyme patterns. The
      results in 33 workers who participated in both studies and had complete sets of
      data are presented. The magnitude of chemical workload was assessed by means of
      ambient air monitoring and biomonitoring of solvent concentrations. Alanine
      aminotransferase, aspartate aminotransferase and gamma-glutamyl transpeptidase
      were used as markers for possible biological effects. No dose-response
      relationship was found between exposure to complex solvent mixtures in ambient
      air, reaching and sometimes even exceeding the threshold limit values for
      mixtures, and liver enzyme activities. Self-reported alcohol intake was the only
      factor identified as statistically related to increased liver enzyme activity.

PMID- 7814093
TI  - Occupational exposure to hydrogen sulfide in the sour gas industry: some
      unresolved issues.
AB  - Occupational exposure to hydrogen sulfide (H2S) and the medical management of H2S
      associated toxicity remains a problem in the sour gas industry and some other
      industrial settings. The acute effects of exposure to H2S are well recognized,
      but accurate exposure-response data are limited to acutely lethal effects, even
      in animal studies. Odor followed by olfactory paralysis and keratoconjunctivitis
      are the characteristics effects of H2S at lower concentrations. H2S-induced acute
      central toxicity leading to reversible unconsciousness is a "knockdown"; it is
      controversial whether repeated or prolonged knockdowns are associated with
      chronic neurologic sequelae but the evidence is suggestive. Knockdowns can be
      acutely fatal as a consequence of respiratory paralysis and cellular anoxia.
      Pulmonary edema is also a well-recognized acute effect of H2S toxicity. Human
      studies of sublethal exposure with satisfactory exposure assessment are almost
      nonexistent. There are indications, poorly documented at present, of other
      chronic health problems associated with H2S exposure, including neurotoxicity,
      cardiac arrhythmia, and chronic eye irritation but apparently not cancer.
      Rigorous and comprehensive studies in the sour gas industry are difficult, in
      part because of confounding exposures and uncertain end points.

PMID- 7814095
TI  - Intervention study on the influence of reduction of occupational exposure to
      styrene on sister chromatid exchanges in lymphocytes.
AB  - An intervention study was performed on 28 workers exposed by inhalation to
      styrene in the reinforced plastics industry and 20 controls not occupationally
      exposed to the compound. The workers involved were 14 laminators exposed to a
      time-weighted average of approximately 40 ppm styrene and 14 formers exposed to
      an average of about 10 ppm styrene. Ambient air monitoring data and the
      concentration of mandelic acid in the urine were used for the assessment of
      exposure. From each subject, peripheral blood lymphocytes were analysed for
      sister chromatid exchanges (SCEs). In the laminators, the mean SCE frequency was
      significantly higher than in the controls in both the group of smokers (9.59 +/-
      0.77 SCEs/cell vs 7.23 +/- 1.00 SCEs/cell) and the group of non-smokers (10.25 +/
      1.08 SCEs/cell vs 5.98 +/- 0.60 SCEs/cell). The mean SCE frequency of the
      formers (7.42 +/- 128 SCEs/cell in smokers) did not differ statistically from the
      controls (7.23 +/- 1.00 SCEs/cell in smokers). No evaluation was made for non
      smoking formers since all but one worker in this group were smokers. In order to
      comply with a lowering of the occupational exposure limit (MAK value) for
      occupational exposure to styrene in the Federal Republic of Germany from 100 ppm
      to 20 ppm, considerable technical and hygienic improvements were made at the work
      site of the laminators. This intervention led to a reduction of average exposure
      of these workers by inhalation from 40 ppm to approximately 20 ppm. One year
      after these improvements were made, a second investigation was performed. In all
      but one of the laminators, the concentration of mandelic acid in urine had
      dropped considerably. The SCE frequency in blood lymphocytes of the laminators
      had likewise dropped significantly to 7.74 +/- 0.59 SCEs/cell in the non-smokers.
      In the smokers, it was also lower than on the first occasion (9.02 +/- 1.19), yet
      statistical evaluation was not possible due to insufficient numbers. Overall, the
      results of the intervention study show that the lowering of the occupational
      exposure limit for styrene to 20 ppm in Germany was justified and that a
      reduction of occupational exposure to the chemical has led to a prevention of
      adverse cytogenetic effects.

PMID- 7814097
TI  - The relations between work demands and health complaints in lorry drivers. A
      model tested by means of LISREL.
AB  - In this study, data of a questionnaire study among 439 lorry drivers were fitted
      to a model in which work demands and the worker's decision latitude are related
      to musculoskeletal complaints and general psychosomatic complaints. Structural
      analysis with LISREL was used to investigate the hypothesized relations. Two
      modifications resulted in a chi 2 of overall fit equal to 77.35 with 47 degrees
      of freedom. The quality of model fit was considered to be satisfactory when the
      sample size was taken into account. The values of the Adjusted Goodness of Fit
      Index (0.948) and the Root Mean Square Residuals (0.029) indicated the same. The
      standardized solution of LISREL showed that work demands with respect to task
      contents were significantly related to musculoskeletal complaints as well as to
      general psychosomatic complaints (0.75 and 0.34 respectively, both P < 0.001).
      This conceptual variable was indicated by physical activities that the drivers
      had to perform. The relations between work-related psychosocial factors and
      musculoskeletal complaints were weak. Another significant effect on general
      psychosomatic complaints was found for work demands with respect to terms of
      employment (0.30, P < 0.001). This conceptual variable was indicated by variables
      concerning working hours and pressure of the work. It is recommended that in
      future occupational epidemiology, both physical and psychosocial aspects of the
      working situation be related to health effects, rather than solely a single
      exposure variable.

PMID- 7814096
TI  - Validity of a diary estimating exposure to tasks, activities, and postures of the
      trunk.
AB  - The validity of a diary that estimates exposure to tasks, activities, and
      postures of the trunk was determined by comparing these self-reported exposure
      data with observational data of a whole working day. Two populations were
      studied: 32 professional drivers and five nurses. The nurses and 16 drivers also
      filled out a shortened version of the diary during another working day. Both
      versions of the diary showed poor agreement with observations over the same
      period. However, for variables concerning activities and postures of the trunk
      agreement was improved by the shortening of the diary. It is concluded that in
      epidemiologic studies observational measurements of exposure cannot validly be
      replaced by diaries or similar self-reported exposure data, because the self
      reports easily lead to misclassification.

PMID- 7814098
TI  - Increased frequency of micronuclei in lymphocytes of Swedish chimney sweeps.
AB  - Forty-five Swedish chimney sweeps and 49 controls were investigated with
      micronuclei stimulated by phytohemagglutinin and pokeweed mitogen and by analysis
      of lymphocyte subgroups and neutrophilic leukocytes. There was a statistically
      significant effect among sweeps with respect to both micronuclei variables and
      neutrophilic leukocytes. The effect on lymphocyte micronuclei was most prominent
      in pokeweed mitogen-stimulated cells, which may imply that the T4 lymphocytes
      were preferentially damaged by the occupational exposure.

PMID- 7814100
TI  - Blood and urinary benzene determined by headspace gas chromatography with
      photoionization detection: application in biological monitoring of low-level
      nonoccupational exposure.
AB  - A simple and sensitive gas chromatography (GC) headspace method was developed for
      the determination of benzene in blood and urine. 1.0 ml of venous blood or urine
      sample in a headspace vial containing chlorobenzene as an internal standard was
      incubated at 60 degrees C for 30 min and 0.5 ml headspace gas was used for GC
      analysis. Unmetabolized benzene in blood or urine was detected at 2.5 min using a
      silicone gum capillary column and a photoionization detector. The proposed method
      appears to be more sensitive and reliable than other existing methods, with
      recovery and reproducibility generally over 90% and a detection limit of 0.64 and
      0.51 nmol/l for blood and urinary benzene, respectively. The proposed method was
      validated with blood and urine samples collected from 25 nonsmokers and 50
      smokers. The blood and urine concentrations of benzene in nonsmokers were
      significantly lower (P < 0.001) than those in smokers: the mean concentrations
      for blood and urinary benzene, respectively, were 1.42 and 4.21 nmol/l for
      nonsmokers and 1.49 and 5.19 nmol/l for smokers. A significant correlation (r =
      0.61, P < 0.001) was also found between benzene in blood and benzene in urine.
      These findings suggest that benzene in urine as well as benzene in blood can be
      used for the biological monitoring of low levels of benzene exposure. Although
      there was a close correlation between benzene in blood and benzene in urine, no
      correlation was found between benzene in blood or benzene in urine and the number
      of cigarettes smoked.

PMID- 7814099
TI  - Incidence of cancer among nitrate fertilizer workers.
AB  - The results are presented from a historical prospective cohort study on the
      incidence of cancer among 1756 male workers at a nitrate fertilizer plant.
      Workers employed for 1 year or more between 1947 and 1980 were included in the
      cohort. Surrogates for individual exposure to nitrogen derivatives and asbestos
      dust were recorded to identify subgroups. There were 195 cases of cancer observed
      versus 208.8 expected, as based on the rates among age-adjusted rural Norwegian
      males. A slight increase in stomach cancer was found: 28 observed versus 19.9
      expected.

PMID- 7814101
TI  - Uptake, metabolism and elimination of cyclohexanone in humans.
AB  - The metabolism and toxicokinetics of cyclohexanone (CH-one), an important solvent
      and chemical intermediate, have been studied in volunteers during and after 8-h
      exposures to CH-one vapour at a concentration of 101, 207 and 406 mg.m-3. The
      pulmonary ventilation in these experiments was typically 11 l.min-1 and retention
      in the respiratory tract was 58%. After exposure to CH-one, 207 mg.m-3, the
      metabolic yields of cyclohexanol (CH-ol), 1,2- and 1,4-cyclohexanediol (CH-diol)
      as determined in urine by a gas chromatographic method involving hydrolysis of
      glucuronide conjugate were 1.0% +/- 0.3%, 39% +/- 5% and 18% +/- 2% (n = 8),
      respectively. Peak excretion of CH-ol was achieved at the end of the exposure
      period, after which it decayed rapidly. Elimination of 1,2- and 1,4-CH-diol
      reached maximum values a few hours following exposure, with subsequent
      elimination half-times of 16 +/- 2 and 18 +/- 4 h, respectively. Repeated
      exposure to CH-one vapour (around 200 mg.m-3) for five consecutive days (8 h/day)
      resulted in cumulative excretion of CH-diols. The permeation rate of CH-one
      liquid through the skin was 0.037-0.069 mg.cm-2.h-1 (n = 3), indicating that the
      contribution of percutaneous absorption to total CH-one occupational intake is of
      minor importance. CH-diols are recommended as biomarkers of exposure to CH-one.

PMID- 7814102
TI  - Long-term mercury excretion in urine after removal of amalgam fillings.
AB  - The long-term urinary mercury excretion was determined in 17 28- to 55-year-old
      persons before and at varying times (up to 14 months) after removal of all (4-24)
      dental amalgam fillings. Before removal the urinary mercury excretion correlated
      with the number of amalgam fillings. In the immediate post-removal phase (up to 6
      days after removal) a mean increase of 30% was observed. Within 12 months the
      geometric mean of the mercury excretion was reduced by a factor of 5 from 1.44
      micrograms/g (range: 0.57-4.38 micrograms/g) to 0.36 microgram/g (range: 0.13
      0.88 microgram/g). After cessation of exposure to dental amalgam the mean half
      life was 95 days. These results show that the release of mercury from dental
      amalgam contributes predominantly to the mercury exposure of non-occupationally
      exposed persons. The exposure from amalgam fillings thus exceeds the exposure
      from food, air and beverages. Within 12 months after removal of all amalgam
      fillings the participants showed substantially lower urinary mercury levels which
      were comparable to those found in subjects who have never had dental amalgam
      fillings. A relationship between the urinary mercury excretion and adverse
      effects was not found. Differences in the frequency of effects between the pre-
      and the post-removal phase were not observed.

PMID- 7814103
TI  - Caries prevalence in the United Kingdom.
AB  - Since 1973, national surveys of dental caries in children, one series directed
      decennially by the Office of Population Censuses and Surveys and another, using
      analogous methods, coordinated regionally on a regular basis by the British
      Association for the Study of Community Dentistry, have produced a comprehensive
      record of trends in caries experience of children in England and Wales. Between
      1973 and 1993 a decline in caries experience of 55 per cent in deciduous teeth of
      5-year-old children, 75 per cent in permanent teeth of 12-year-old, and 74 per
      cent in 14-year-old children, was documented. However, the most recent surveys,
      carried out since the end of the 1980s, suggest that caries levels have now
      levelled out and may even have started to rise in younger children while in
      adolescents the rate of decline has slowed substantially. Possible explanations
      for these trends are discussed. The national data conceal wide disparities
      between different regions of the country and a notable worsening in the caries
      experience of children in lower socio-economic groups. In order to consolidate
      the gains of the last 20 years and safeguard the future dental health of both
      children and adults, implementing population preventive methods such as water
      fluoridation should be vigorously pursued.

PMID- 7814104
TI  - Caries prevalence in the Nordic countries.
AB  - Despite differences in the dental health care services and the recording and
      reporting systems, a consistent and similar decline in dental caries is evident
      for Denmark, Finland, Norway and Sweden during the last two decades. Iceland has
      experienced a later onset but a steeper decline in dental caries than the other
      Nordic countries. Public reports demonstrate that in 1991/92 23-49 per cent of
      the 12-year-old children were caries-free and the mean tooth prevalence was 1.2
      2.5 DMFT. Fluoride in various forms has been instrumental in these changes, and
      public dental health programmes appear to have played an important role, at least
      in the initiation of the decline. Caries has been slowed down and delayed, but
      has not been eradicated.

PMID- 7814105
TI  - Caries prevalence in Belgium and The Netherlands.
AB  - A list of epidemiological caries studies performed since 1980 in Belgium and The
      Netherlands was compiled by a literature search and analysed with respect to
      study design, methods of clinical investigation and the availability of dmft
      (DMFT) data. The percentages of caries-free 6-year-old children in The
      Netherlands and Belgium are currently similar. In The Netherlands the data
      suggest a halt in the decline of caries prevalence since the mid 1990s among 6
      year-olds. According to WHO criteria, 12-year-old children in The Netherlands now
      have a very low caries experience. Children in Belgium belong to the moderate
      caries experience category. Recent data from the two countries indicate a further
      decrease in caries prevalence of 12-year-olds during the last decade. Caries
      prevalence data of adults in Belgium are not available. In The Netherlands the
      average DMFT-score in the older age groups has hardly changed since 1970. Changes
      in percentages of edentates in the period 1980-1990 probably reflect part of the
      changes in oral health status of Dutch adults. The intervention of many
      methodological problems and confounding factors, such as cultural differences,
      limit national and international comparisons of caries prevalence data sets.

PMID- 7814106
TI  - Caries prevalence in the Republic of Ireland.
AB  - The implementation of the Health (Fluoridation of Water Supplies) Act 1960 was
      preceded by a survey of child dental health in the Republic of Ireland. A follow
      up national survey in 1982 showed that caries had declined in both fluoridated
      and non-fluoridated communities, although more so in the former. An adult dental
      health survey reported in 1992 showed that tooth loss had declined in the period
      1979 to 1989.

PMID- 7814107
TI  - Caries prevalence in Switzerland.
AB  - The first Swiss studies of DMFT counts were undertaken in the late 1950s and
      showed values of 7.7-11.3 for children of 12 years of age and 12.6-18.6 for
      children of 15 years of age. Although these studies did not use current
      statistical sampling methods, and so are not directly comparable, the results of
      the most recent surveys do present a startling contrast. In 1992, DMFT figures
      had fallen to an average of 1.12 and 2.22 DMFT in 12- and 15-year-olds
      respectively. Reasons for these sharp declines are discussed, as are the
      available figures for adults over the same period of time. Predictions are made
      for DMFT levels for the year 2008 and their likely impact on dental services.

PMID- 7814108
TI  - Trends in caries prevalence in North American children.
AB  - Data for caries in the permanent and primary dentitions of children in Mexico,
      the United States, and Canada are reviewed from the years around 1982 to the
      present time. Sources are national, state, and provincial surveys, together with
      a number of smaller, local surveys. Data from minority populations are also
      reviewed. Conclusions are that caries prevalence and severity in the permanent
      dentition are continuing to decline in the general populations of Canada and the
      United States, but that caries experience in the primary dentition may have
      stabilised since around 1986-87. There is nothing in the limited data available
      from Mexico to suggest a decline in that country, caries levels remaining high.
      There are considerable geographic variations in caries experience in the general
      populations of the United States and Canada; the highest prevalence and severity
      is found in Quebec. Caries is more prevalent and severe in the indigenous
      populations of Canada and the United States than in the general population, but
      there are indications of a decline in the permanent dentitions of those
      indigenous groups. Caries will probably decline further in the general
      populations of Canada and the United States before it reaches an irreducible
      minimum, but that point may not be far away because caries experience is already
      very low in many localities. It is anticipated that the recent introduction of
      salt fluoridation in Mexico will help to bring down the high caries levels in
      that country.

PMID- 7814109
TI  - Caries prevalence in Australasia.
AB  - The prevalence of caries in Australian children has decreased markedly since its
      peak in the 1950s. More than half the child population has no experience of
      caries. However, a small minority, approximately one in sixteen, may be
      considered still at high risk with an unacceptably large number of teeth with
      caries experience. This is leading to the addition of high risk strategies to
      programmes for caries prevention and management. While the prevalence of caries
      in children has decreased, caries experience in adults has remained widespread
      and extensive. The majority of teeth in dentate adults have experienced caries.
      Comparisons over time indicate little change in caries experience in middle-aged
      adults, but an increase in filled teeth and decrease in missing teeth. The
      prevalence of caries has not changed substantially, but the management of the
      disease has moved towards maintenance and repair of teeth. Tooth retention has
      increased over recent decades. Edentulism has decreased markedly and dentate
      adults are retaining more teeth. Sizeable increases in the pool of teeth at risk
      of caries give emphasis to the continued need for preventive measures to reduce
      caries activity in adults.

PMID- 7814110
TI  - Caries prevalence in Africa and the People's Republic of China.
AB  - Problems arise when attempting to compare caries data collected in both Africa
      and the People's Republic of China. These difficulties are not only the result of
      differences in the criteria used for the diagnosis of caries but are also due to
      the diversity of cultural and social conditions existing within each of the
      geographical areas. However, interpreted with caution, the data seem to suggest
      that caries experience among children is still fairly stable and at a low level,
      in contrast to the predictions of a decade ago. When comparing data from adult
      and elderly cohorts, however, caries is seen to be a widespread disease with
      continuing slow progression throughout life.

PMID- 7814111
TI  - The effect of changes in caries prevalence on general dental practice.
AB  - There have been many changes in the organisation and structure of general dental
      practice in the UK in recent years. Some of these have been due to the changes in
      caries prevalence. Other changes have been caused by shifts in the system of
      remuneration under the National Health Service (NHS), which may themselves have
      been influenced by falling caries levels. It is also pertinent to consider the
      ways in which dental practice has affected caries rates, since, arguably some of
      the changes in caries prevalence have been due to developments in dental
      practice.

PMID- 7814113
TI  - The effect of changes in caries prevalence on dental education.
AB  - While rising levels of dental caries were primarily responsible for the growth in
      dental schools in developed countries, the recent decline in caries prevalence
      has not resulted in a major decline in dental education. Indeed, the reduction in
      caries prevalence has had very little influence upon a group of major changes
      that arguably should have had a marked effect upon dental education in recent
      years, but which have failed so to do. These include a quantum leap in applying
      the scientific basis of caries management, focused down to the teaching of
      minimally invasive restorative care within a context of risk assessment and
      maximum non-invasive care where appropriate. A possible way forward in
      accelerating the necessary changes in dental practice would be for only a
      proportion of dental undergraduates in the future to be taught practical
      restorative procedures, leaving the remainder to concentrate on diagnostic and
      non-invasive care without the distraction of possible restorative treatment.

PMID- 7814112
TI  - The effect of changes in caries prevalence on oral health promotion--the United
      Kingdom experience.
AB  - Caries reductions have occurred in the majority of industrialised nations but the
      impact of these changes in dental disease on oral health promotion activity is
      not clear. A pilot study recorded the views of members of the Oral Health
      Promotion Research Group on how they had modified their approach to the task of
      providing appropriate oral health promotion. Two thirds stated that the caries
      reductions were not evident in the populations they served and the remainder were
      able to target interventions more accurately following the decline in caries.
      This pilot study has highlighted the fact that caries reductions are not
      universal and the reasons why some groups in society have not achieved a 'dental
      health gain' requires further investigation.

PMID- 7814114
TI  - Implications of changes in caries prevalence on research.
AB  - The marked decline of caries prevalence in some populations should be an
      incentive for research to reduce caries prevalence as well in (sub)populations
      which have not benefited equally. Epidemiological studies, including data on the
      increasing numbers of elderly subjects, will remain important in the future;
      epidemiologists require better methods of diagnosing small lesions and of
      identifying risk groups. Sophisticated computer simulation models for the
      processing of epidemiological data might result in more accurate predictions and
      may enable health policy planners to invest scarce funds in the most efficient
      manner. These efforts should be focused on improving school health education and
      prevention strategies in general. The main difference between (sub)populations
      with low caries prevalence and high caries prevalence seems to be the lack of
      regular toothbrushing with a fluoride toothpaste by members of the high
      prevalence subpopulation. Since, in many countries, toothbrushing has been
      accepted by 80 per cent of the population, it should be possible to get this
      habit adopted by the minorities still at high risk. Future research with the
      highest priority should be behavioural studies into (dental) health education
      with personal hygiene as the main goal. Socio-psychologists should conduct
      research into the possibilities of motivating people to practice oral hygiene and
      hygiene-minded behaviour in general. This would not only improve oral health, but
      at the same time would tackle what still is the greatest threat to mankind:
      infectious diseases.

PMID- 7814115
TI  - Comments on results reported at the Second International Conference 'Changes in
      caries prevalence'.

PMID- 7814116
TI  - An atraumatic restorative treatment (ART) technique: evaluation after one year.
AB  - Extraction is the most common dental treatment provided for people in rural and
      suburban areas in many less-industrialised countries. By comparison, restorative
      care is rarely provided. In order to improve such situations, a treatment
      technique has been developed based only on hand excavation of carious lesions and
      using glass-ionomer cement as a filling material and a sealant. This Atraumatic
      Restorative Treatment (ART) technique follows the concept of minimal intervention
      and does not require electrically driven equipment. This paper reports on the
      longevity of fillings and sealants placed using the technique under field
      conditions in rural Thailand. Dental caries was treated using the ART technique
      in one village, whilst the population in a second village received restorative
      care (amalgam fillings) through mobile dental units. A third village was the
      control. After one year, 79 per cent of single surface ART fillings and 55 per
      cent of ART fillings of greater than one surface placed in deciduous teeth were
      judged successful. The success rate of ART fillings in the permanent dentition
      (mainly single surface fillings) was 93 per cent and the retention rate for
      sealants was 78 per cent. Children were pleased at having received treatment by
      this technique and showed little fear. The ART technique is a promising caries
      treatment procedure for use in rural and sub-urban areas in less-industrialised
      countries.

PMID- 7814117
TI  - A clinical comparison of non-traumatic methods of treating dental caries.
AB  - Over a period of 18 months the following non-traumatic methods of treating dental
      caries in deciduous teeth were compared: application of stannous fluoride (SnF2);
      application of SnF2 and silver diamine fluoride (SDF); application of SnF2, SDF,
      minimal cavity preparation and use of composite resin; minimal cavity preparation
      and composite resin only; no treatment. Caries progressed in only 5 per cent of
      the SDF/SnF2 group and 11 per cent of the composite resin group. The results
      indicate that it may be possible to treat carious lesions in a non-traumatic way
      using minimally prepared cavities and composite resin. This could significantly
      alter the restorative care of deciduous molars and it may be reasonable to
      speculate that the technique could also have important implications for use in
      the permanent dentition.

PMID- 7814118
TI  - A risk-related patient-administered medical questionnaire for dental practice.
AB  - This study deals with an improved medical questionnaire designed on the basis of
      the results of previous studies. The form consists of 27 items, each subdivided
      into a main question and one or more subquestions. The medical problems involved
      are categorised according to the risk-classification system of the American
      Society of Anaesthesiologists (ASA). An affirmative answer to the main question
      always results in ASA class II; the subquestions are designed to discriminate
      between ASA classes II, III and IV. For each of the 27 medical problems in the
      questionnaire, the implications for dental treatment are explained and an ASA
      risk classification proposed. The questionnaire can also be a useful tool in
      medical pre-assessment control.

PMID- 7814119
TI  - Prevalence of dental caries among Ethiopian emmigrants.
AB  - Studies have documented the prevalence of caries in developing countries. The
      current study adds to this body of knowledge. Of the total Ethiopian Jewish
      population who emmigrated to Israel in 1991, a sample of over 800 individuals was
      randomly selected representing all age groups. DMF-T and DMF-S scores were
      recorded, as well as percentages of caries free individuals. Results indicated
      that almost no fillings or crowns had been provided to the study population. The
      Missing 'M' component was low as was the Decay 'D' component, although this
      increased with increasing age, ranging from 0.33 D-T at the 0-12 age group to
      2.46 at the 51+ age group. In the permanent dentition 88.4 per cent of those 0-12
      years of age were caries free and 74.5 per cent were caries free in both the
      primary and permanent dentition. Almost 59 per cent of the 13-20 years olds were
      caries free and 32.8 per cent of those 21-50 years old. Only 16.7 per cent were
      caries free at age 51+ years old. The data indicate a relatively low prevalence
      of both coronal and root caries, and an effort has to be made to keep these
      figures low for years to come mainly by diet and dental health education.

PMID- 7814120
TI  - A review of the current approaches to the management of the severely reduced
      dentition.
AB  - The severely reduced dentition is a continual challenge to the treatment planning
      skills of the restorative dentist. This paper examines the need for treatment in
      the context of oral function, social requirements and related disease processes.
      The philosophy for management should be based on sound knowledge of the outcomes
      of treatment options. This paper highlights the relevant factors to be assessed
      in treatment planning for the severely reduced dentition.

PMID- 7814121
TI  - Comparing perceptions of dental aesthetics in the USA with those in eleven ethnic
      groups.
AB  - The Standard DAI is an orthodontic index based on perceptions of dental
      aesthetics in the USA. The Standard DAI is a regression equation linking
      perceptions of the social acceptability of dental aesthetics with the objective
      intraoral measurements of ten occlusal traits. Since the Standard DAI is based on
      perceptions of dental aesthetics in the USA it can be used without modification
      only where perceptions of dental aesthetics are similar to those in the USA. This
      study was designed to determine whether perceptions of dental aesthetics of
      students in eleven diverse ethnic groups are similar to those of students in the
      USA. The same 25 stimuli (photographs of dental configurations, a subset of the
      200 stimuli used in deriving the Standard DAI equation) were rated for dental
      aesthetics by Australian, Chinese, German, Japanese, Korean, Latvian, Native
      American, Singaporean Chinese, Singaporean Indian, Singaporean Malay, and Thai
      students. Their ratings were compared with the ratings of the same 25 stimuli by
      students in the USA. Spearman rank-order correlations ranged from 0.84 to 0.94.
      These correlations are sufficiently high to show that perceptions of dental
      aesthetics in all eleven ethnic groups are very similar to the perceptions of USA
      students. Therefore the Standard DAI can be used without modification in all
      eleven ethnic groups.

PMID- 7814123
TI  - Worldwide survey on distance learning in dental education.
AB  - This paper reports the results of a worldwide survey on distance learning
      initiated by the FDI. The results indicate that dental associations in many
      countries are in the process of investigating the various options available, and
      in development, for bringing continuing education to their members with the
      maximum convenience and effectiveness. Details are given of advantages,
      disadvantages and relative costs of the different methods undertaken.
      Recommendations are made for future development and progress.

PMID- 7814122
TI  - Who needs clinical audit?
AB  - Clinical audit focuses on self--and, more importantly, peer assessments of the
      performance of practitioners and the service they provide to patients. Some
      practitioners may feel threatened by audit; however, when conducted as intended
      and viewed as a form of education, it may become recognised as an integral, cost
      effective element of everyday clinical practice. This article highlights ways in
      which practitioners may increasingly appreciate the need to understand and apply
      clinical audit processes in their practice environments.

PMID- 7814124
TI  - Participatory continuing dental education.
AB  - The significance of continuing education for the development of a professional
      person is indisputable. There is evidence that participatory continuing education
      is the most effective form for this activity to take in relation to dentists and
      clinical practice. Working Group 15, appointed by the FDI Commission,
      specifically studied this form of continuing education by use of a questionnaire
      to 26 representative national dental associations. The majority of countries
      surveyed have at least some education of this sort although it forms only a small
      proportion overall. Little evaluation seems to take place to measure the
      subsequent value to the practitioners attending. The results of the information
      gathered are discussed and recommendations are made.

PMID- 7814125
TI  - Cytotoxicity studies of dental restorative materials using human periodontal
      ligament cells in vitro.
AB  - A model that simulates conditions of clinical practice in vivo and allows
      extended exposure of test cells to test substances, was evaluated in vitro by
      screening the toxicity of seven dental restorative cements. Millipore filter
      discs, 0.45 micron pore size, or preserved dentine slices were used as diffusion
      barriers between test cells and test substances. Cytotoxicity was assessed by
      estimating cell loss from monolayers and by evaluating cytopathic changes in
      cultured cells. After 24 h exposure to the test materials results were in general
      agreement with reported observations from similar studies. However, extended
      exposure to composite resins gave rise to severe cytotoxicity, which has not been
      reported previously. In addition, monitoring of cultures by inverted microscopy
      demonstrated attempts at recovery in damaged monolayers with viable cells
      migrating and proliferating into areas of earlier cell loss. This supports
      observations in vivo of transient pulpal injury associated with the corresponding
      materials.

PMID- 7814127
TI  - A morphometric analysis of the cross-sectional area of dentine occupied by
      dentinal tubules in human third molar teeth.
AB  - The number and the mean percentage tubular cross-sectional area of dentinal
      tubules per square millimetre were calculated in specimens of coronal dentine of
      13 intact human third molar teeth from patients 18 to 28 years of age. The
      dentine was fractured at various known distances from the dentino-enamel
      junction. Near the dentino-enamel junction the number of tubules per square
      millimetre was 22,000 and the mean tubular cross-sectional area was 3.6%. Midway
      between the pulpal wall and the dentino-enamel junction the number of tubules was
      37,000 mm-2 and the mean tubular cross-sectional area was 6.2%. Close to the pulp
      the number of dentinal tubules was 48,000 mm-2 and the mean cross sectional area
      of tubules was 10.2 percent. The number of tubules per square millimetre more
      than doubled and the area occupied by tubules increased threefold from the
      dentine close to the dentine-enamel junction, to that close to the pulp. These
      differences in tubular patterns at different depths in dentine are clinically
      significant in dentine permeability, the treatment of traumatized teeth, and pain
      transmission in dentine.

PMID- 7814126
TI  - Comparison of the quality of obturation following endosonic versus hand
      instrumentation.
AB  - This study was undertaken to compare the quality of root canal obturation
      following preparation by endosonic or hand instrumentation. Forty single-canal,
      extracted lower premolar teeth were selected. One group of 20 teeth was prepared
      using a standard step-back technique, the other 20 teeth were prepared with an
      ultrasonic machine. The groups were subdivided, with two operators preparing 10
      teeth of each group. The teeth were obturated by a third operator using cold
      laterally condensed gutta percha. The root apices were then immersed in methylene
      blue dye for 48 h and the teeth sectioned longitudinally. Image analysis recorded
      the amount of sealer and void within the obturated canal. The linear distance of
      dye penetration was measured to provide an indication of apical seal. Examination
      of the root canal shape resulting from the different preparation techniques used
      was also undertaken. No significant difference was noted in the percentage of
      sealer and void present in the root canals obturated after endosonic or hand
      instrumentation. There was a slightly greater although not significant increase
      in the degree of linear penetration of dye in canals prepared endosonically. The
      endosonic technique used in this study appeared to produce a canal preparation of
      slightly less continuous taper than that obtained with hand preparation.

PMID- 7814128
TI  - An in-vitro evaluation of the influence of canal curvature on the sealing ability
      of Thermafil.
AB  - The sealing ability of lateral condensation and Thermafil were compared in root
      canals with curvatures either greater or less than 25 degrees. Forty-eight canals
      in roots of extracted human mandibular molar teeth were divided into four groups
      of 12. The root canals in two groups had curvatures of less than 25 degrees and
      the remaining two groups had canals with curvatures greater than 25 degrees. Four
      canals acted as positive and negative controls. All canals were enlarged to
      accept a size 30 file to the working length and flared using the step-back
      technique. Roth's sealer was used in all canals. Lateral condensation and
      Thermafil obturators thermoplasticized in an open flame were used to obturate two
      groups each of canals, one group with curvatures greater than 25 degrees and the
      other less than 25 degrees. After immersion in India ink, the teeth were rendered
      transparent and the linear penetration of dye measured. It was found that
      Thermafil sealed significantly better than lateral condensation in canals with
      curvatures greater than 25 degrees (P < 0.05). However, there were no significant
      differences between the techniques in the groups with canal curvature less than
      25 degrees. There was no significant difference in the performance of each of the
      techniques when analysed with respect to canal curvature.

PMID- 7814129
TI  - Physical mechanisms governing the hydrodynamic response of an oscillating
      ultrasonic file.
AB  - Ultrasonically driven vibrating files are known to enhance the efficiency of root
      canal debridement. This paper presents a phenomenological view of the
      hydrodynamic response of an oscillating ultrasonic file and the relationship
      between the file response and various physical factors such as file size and
      curvature, file surface properties, file velocity amplitude, root canal geometry,
      and the type of irrigant. Relevant hydrodynamic properties include the propensity
      of a file to produce stable and transient cavitation, steady streaming, and
      cavitation microstreaming. These relationships were explored by experiment.
      Sonoluminescence was employed as an indicator of transient cavitation activity
      and photographic analysis was utilized as a means for detecting steady streaming,
      microstreaming, and stable cavitation. Measurements failed to indicate any strong
      correlation between registered driving power and the propensity to produce
      transient cavitation. Files that were pitted or possessed salient edges were very
      effective at generating transient cavitation. When observed, transient cavitation
      activity generally occurred near the tip of the straight file, provided the wall
      loading did not inhibit file motion. In all cases studied, steady streaming and
      stable cavitation were observed to varying degrees, depending on the amount of
      file to wall contact. Stable cavitation was probably enhanced by the addition of
      moderate amounts of dissolved gas into the irrigant. Although the imposition of
      file-wall contact served to inhibit the production of transient cavitation, this
      action had relatively little effect on the ability of a file to produce a nominal
      level of streaming, microstreaming, and stable cavitation. The relationship
      between these hydrodynamic properties and the process of root canal debridement
      is addressed. Observations suggest that it is not prudent to ascribe enhanced
      cleaning effects to any one phenomenon, for it is likely that several factors are
      involved to varying degrees depending on the local conditions of application.

PMID- 7814130
TI  - Assessment of coronal leakage in teeth root filled with gutta-percha and a glass
      of ionomer root canal sealer.
AB  - The effect on coronal leakage of the use of either a single gutta-percha cone or
      cold lateral condensation of gutta-percha, with a glass ionomer sealer cement was
      studied. In addition, the effect of the removal of the smear layer was also
      determined. Eighty-eight single-rooted teeth were prepared chemomechanically
      using hand files, with the balanced force technique. Lubrication was provided by
      either Hibiscrub (maintaining the smear layer) or an EDTA-containing paste (to
      remove the smear layer). Copious irrigation was carried out with 2.2% sodium
      hypochlorite. The teeth were allocated randomly to four groups of 20 teeth each,
      the remaining eight teeth served as controls. Two groups of teeth, one with and
      one without smear layer, were obturated with either a single gutta-percha cone or
      cold laterally condensed gutta-percha, with Ketac Endo as the sealer. The teeth
      were stored for 6 weeks, thermocycled, and the extent of coronal leakage
      determined for each group after immersion in India ink for 90 h. The teeth were
      demineralized, dehydrated and immersed in methyl salicylate, which rendered them
      transparent. Linear measurement of maximum dye penetration was recorded. The mean
      depth (+SD) of leakage for the groups in which the smear layer was left intact
      was 1.68 mm (+0.38) for the single cone (A1) and 2.29 mm (+1.58) for lateral
      condensation (B1). When the smear layer was removed the mean depth of leakage for
      the single cone group (A2) was 2.04 mm (+0.73) and 2.37 mm (+1.70) for the
      laterally condensed group (B2). There was no significant difference in coronal
      leakage between the groups (P > 0.05).

PMID- 7814131
TI  - In vitro evaluation of apical leakage of root canal fillings after in situ
      obturation with thermoplasticized and laterally condensed gutta percha.
AB  - The purpose of this investigation was to compare in vitro the sealing ability of
      root canal treatments performed in situ with injected thermoplasticized gutta
      percha compared with the lateral condensation technique. Thirty single-rooted
      teeth with straight canals, due for extraction for orthodontic or periodontal
      reasons were prepared using a step-back technique. Teeth were then divided
      randomly into groups A and B and obturated, respectively, with the sectional
      injection thermoplasticized gutta-percha and the lateral condensation techniques.
      Teeth were extracted after 15 days, immersed in India ink for 3 days and the
      leakage was determined using area-metric analysis. The roots were ground
      transversally and the root portion was incrementaly removed with successive steps
      of 250 microns each, up to the coronal level of the dye penetration. Every
      section was photographed with a stereoscopic microscope under the same
      magnification (x20); 310 photographs were taken. Measurements of the area covered
      by ink as well as the whole cross-sectional area of the canal were made from each
      photograph with the aid of a digitizing computer. The measurements were subjected
      to non-parametric statistical analysis. No significant difference was found (P >
      0.05). The technique of lateral condensation proved to be better in the first
      five sections (1.2 mm from the foramen) while thermoplasticized gutta-percha
      technique was superior in the rest of the root canal.

PMID- 7814132
TI  - Dentine tubule infection and endodontic therapy implications.
AB  - A critical review of the literature suggests that the microenvironment of
      dentinal tubules appears to favour the selection of relatively few bacterial
      types irrespective of the aetiology of the infection process; coronal dental
      caries or pulpar necrosis. These bacteria may constitute an important reservoir
      from which root canal infection and reinfection may occur following pulp necrosis
      or during and after endodontic treatment. Previous studies of this microflora
      have utilized microbiological culture techniques which need to be supplemented by
      those that allow in situ demonstration as well as identification of the bacteria.
      Newer treatment strategies that are designed to eliminate this microflora must
      include agents that can penetrate the dentinal tubules and destroy these
      microorganisms, since they are located in an area beyond the host defence
      mechanisms where they cannot be reached by systemically administered
      antimicrobial agents.

PMID- 7814133
TI  - Effect of addition of hydroxyapatite on the physical properties of IRM.
AB  - The aim of this study was to evaluate the effect of adding 10% and 20%
      hydroxyapatite (HAP) to Intermediate Restorative Material (IRM) on physical
      properties such as working time, setting time, compressive strength and
      disintegration rate. The working and setting times were determined by an
      indentation method. The ISO recommended method was used to determine compressive
      strength. The rate of disintegration in vitro was evaluated in buffered sodium
      citrate at pH 4.5, 5.8, buffered phosphate at pH 7.0 and in bovine serum (pH
      6.8), and examined using a replica method and scanning electron microscopy.
      Kalzinol and EBA were used as control materials for the disintegration
      experiment. IRM had longer mean working (4 min 43.5 s) and mean setting (6 min
      28.5 s) times than IRM + 10 or 20% HAP (P < 0.001), the mean reductions being 16%
      and 9% for IRM + 10% HAP, and 29% and 19% for IRM + 20% HAP, respectively. IRM
      had a greater compressive strength (68.5 MPa, P < 0.01) than IRM + 10% HAP (65.0
      MPa) or IRM + 20% HAP (60.0 MPa, P < 0.001). Kalzinol, IRM + 10% HAP and IRM +
      20% HAP were found to disintegrate after 8 weeks in buffered phosphate and in
      bovine serum. In contrast, IRM and EBA showed no noticeable signs of
      disintegration after 6 months in the same media. The physical properties of IRM +
      10% HAP and IRM + 20% HAP were reduced compared with IRM but the reductions were
      not considered to be of clinical significance.

PMID- 7814134
TI  - Fluid transport and dye penetration along root canal fillings.
AB  - Dye penetration along root canal fillings may be hindered by the presence of
      entrapped air. In this study, the sensitivity of a dye penetration method was
      compared with that of a fluid transport model. Sixty root sections from human
      maxillary central incisors were prepared and obturated by a modified technique to
      ensure a slight amount of leakage, and divided into three equal groups. Twenty
      root sections were first mounted in a fluid transport device and assessed for
      fluid transport under 10 kPa (0.1 atm.) pressure. Another 20 root sections were
      mounted in the same device before being subjected to air transport under the same
      pressure. The remaining 20 root sections were not exposed to fluid or air
      transport. Then, all the 60 root sections were assessed for penetration of a 2%
      methylene blue solution. The results showed that fluid transport was a much more
      sensitive method of detecting voids along root canal fillings than dye
      penetration. After fluid transport for 3 h under low pressure, to eliminate
      entrapped air, dye penetrated significantly deeper than without previous fluid
      transport, which suggested that entrapped air in voids along the root canal
      filling prevented dye penetration.

PMID- 7814135
TI  - Sealing properties of Ketac-Endo glass ionomer cement and AH26 root canal
      sealers.
AB  - Sealing capacity, setting shrinkage and setting time of a recently introduced
      glass ionomer cement Ketac-Endo were compared with that of a conventional sealer
      AH26. Sixty half-cylinders, 8 mm long, 4 mm in diameter, made from fresh bovine
      root dentine, had their smear layer removed before being cemented together while
      separated by 1-mm spacers. This resulted in a group of 15 cylinders cemented with
      Ketac-Endo and a similar group with AH26. After coating the lateral surface with
      nail varnish, one end of each cylinder was connected with a tube filled with
      water under 120 kPa (1.2 atm) pressure. At the other end the fluid leaking
      through the cemented interface of the cylinders was measured by displacement of
      an air bubble in an attached standard glass capillary. In this particular set-up
      where the sealers were used in bulk between two opposing dentine surfaces, Ketac
      Endo leaked significantly more than AH26. After shear loading the cemented
      specimens, it was found that the area of adhesive failure was 88% for Ketac-Endo,
      and 15% for AH26. The leakage pathways were most probably at the dentine-sealer
      interface for Ketac-Endo and through cohesive fractures in the sealer for AH26.

PMID- 7814136
TI  - Irritating effect of formocresol after pulpectomy in vivo.
AB  - A study was carried out to investigate the effect of formocresol (formalin
      creosote) on the periapical tissue after pulpectomy in rats. A pulpectomy was
      performed on the mesial root of the right mandibular first molar, and, in group
      A, a paper point containing saline was inserted into the root canal. In group B,
      a paper point containing formocresol was inserted, and in group C, a drop of
      formocresol was applied and a paper point containing formocresol was inserted
      into the root canal. The periapical tissue was examined histologically and
      histometrically at 3, 7, 14, and 28 days after insertion, and the inflammatory
      cells and fibroblasts in the apical granulation tissue were also counted.
      Histologically, in group A, the inflammation observed was slight at 14 and 28
      days, while in groups B and C, a moderate inflammation remained. Histometrically,
      the area of the apical periodontal ligament in groups B and C was increased
      significantly compared with that in group A at 14 and 28 days. The inflammatory
      cell count in groups B and C increased significantly compared with that in group
      A at 7, 14, and 28 days, whereas the fibroblast count in Groups B and C decreased
      compared with that in Group A at 7, 14, and 28 days. These results demonstrate
      that formocresol delayed the healing of periapical tissue after pulpectomy.

PMID- 7814137
TI  - The effect of storage time on the degree of dye leakage of root-end filling
      materials.
AB  - The quality of the apical seal obtained by root-end filling materials generally
      has been assessed by the extent of dye penetration. Most investigators have
      allowed the root-end filling materials to set before they are tested. The purpose
      of this study was to evaluate if storage time had any influence on the amount of
      dye leakage. Seventy extracted single rooted human anterior teeth were used.
      After removal of their anatomical crowns, the roots were instrumented, filled
      with gutta-percha and Roth's sealer, and subjected to test conditions. The roots
      were coated with two coats of nail polish. Root ends were resected and class I
      cavities prepared. Sixty class I root-end cavities were filled with with either
      amalgam, super EBA, or IRM (20 each). Ten roots in each group were placed
      immediately into India ink for 48 h, the other 10 were stored for 24 h before
      placement into the ink. Ten roots (five per group) were used as positive (gutta
      percha, no sealer) and negative (bone wax) controls. The roots were then
      demineralized, linear dye leakage was measured, and the data were evaluated
      statistically using ANOVA. Super EBA, and IRM showed significantly less dye
      leakage than amalgam (P < 0.0001). No significant difference existed between
      Super EBA and IRM. Storage time had no significant influence on the amount of dye
      leakage observed in this study.

PMID- 7814138
TI  - A study in vitro of threaded titanium pins used for retrograde obturation of root
      canals.
AB  - The microleakage of four retrograde filling materials was compared in vitro.
      Fifty-three single rooted teeth were instrumentated and root filled with resin
      chloroform and gutta-percha. The gutta-percha cones were left extruding from the
      access opening. All teeth were apicected and retrograde fillings placed. The
      materials used were a non gamma 2 amalgam (Amalcap), a glass ionomer cement
      (ChemFil II), threaded titanium pins cemented with a glass ionomer cement
      (ChemFil II) and identical titanium pins cemented with a silicone material
      (Adheseal). After removal of the gutta-percha with tweezers, a radioactive
      isotope solution was placed in the teeth. Extraradicular samples were taken at 3,
      7, 28, 77 and 104 days. All retrograde fillings showed some microleakage. The
      group with titanium pins cemented with silicone showed the least leakage:
      significantly less than the teeth with glass ionomer cement (P < 0.01) and with
      amalgam (P < 0.01). No significant differences were found between other groups.

PMID- 7814139
TI  - Endodontic references and abstracts.

PMID- 7814140
TI  - Strategies for global control of cervical cancer.

PMID- 7814141
TI  - Characterisation of four Merkel cell carcinoma adherent cell lines.
AB  - We have previously described the establishment of a number of cell lines from
      Merkel cell carcinoma (MCC), also known as small cell cancer of the skin or
      neuroendocrine carcinoma of the skin. These cells, all of which grew as
      suspension cultures, were found to resemble small cell lung cancer (SCLC) lines
      types 1, 2 and 3 by their morphology and growth characteristics. We now report 4
      more MCC cell lines which resemble the SCLC type 4 cell lines in that they grow
      as adherent monolayers. These MCC lines would belong to the variant subgroup as
      they no longer express most neuroendocrine markers, grow at low cell density and
      have population doubling times of 1-5 days in contrast to the MCC suspension
      lines which have doubling times of 6-12 days. MCC14/1 and MCC14/2 were
      established from the same metastatic node and would appear to represent 2 clones
      of the tumour which differ in morphology, histochemical markers and DNA content.
      We present details of the morphology, DNA content and immunohistochemistry of
      these 4 lines and compare their growth patterns with those of SCLC and MCC lines
      which grow in suspension.

PMID- 7814142
TI  - Nuclear DNA content and chromatin texture in multidrug-resistant human leukemic
      cell lines.
AB  - Nuclear morphological alterations associated with multidrug resistance (MDR) were
      evaluated by image cytometry in various human leukemic cell sub-lines: 3 cell
      lines with P-gp-mediated resistance (CEM-VLB, HL60/Vinc, K562-Dox), the non-Pgp
      mediated MDR HL60/AR leukemic cell line with over-expression of MRP, and the at
      MDR CEM-VMI leukemic cell line with alteration of topoisomerase II. All these MDR
      cell sub-lines were obtained by drug selection and were compared with their
      sensitive counterparts and with the hamster LR73-R cell line obtained by
      transfection of mouse mdrl cDNA. All MDR cell sub-lines obtained by drug
      selection displayed decreased DNA Feulgen stainability as compared with their
      respective sensitive parental cell line, a phenomenon not observed in the
      transfected LR73-R cells. Nuclear texture analysis on G0/G1-selected cell nuclei
      revealed 2 types of textural phenotype. The first phenotype was characterized by
      chromatin decondensation with small but compact chromatin clumps, and was
      observed in drug-selected P-gp-mediated MDR cells (CEM-VLB, HL60-Vinc, K562-Dox)
      and in the non-P-gp-mediated MDR HL60/AR cell line. The second phenotype was
      characterized by a condensed and homogeneous chromatin pattern, and was observed
      in the at-MDR CEM-VMI cell line. LR73-R cells transfected with mdrl cDNA did not
      display any significant changes in textural phenotype as compared with sensitive
      LR73 cells, suggesting that P-gp over-expression alone cannot account for the
      cytological modifications observed in MDR cells. These data suggest that
      multidrug resistance could be associated with specific nuclear morphological
      changes which appeared to be a consequence of alterations occurring during
      selection by cytotoxic drugs rather than of P-gp over-expression.

PMID- 7814144
TI  - Reverse-zymographic analysis of protease nexin-II/amyloid beta protein precursor
      of human carcinoma cell lines, with special reference to the grade of
      differentiation and metastatic phenotype.
AB  - Trypsin inhibitors in serum-free conditioned media (SFCM) of various human
      carcinoma cell lines were analyzed by reverse zymography. Most of the cells
      secreted high-molecular-weight trypsin inhibitors (HMTI) larger than 100 kDa. The
      cell lines of colorectal carcinoma origin had a tendency to secrete HMTI whose
      molecular weight was a little higher than that of the other cell lines. Analysis
      of SFCM of subclones with different histological differentiation and
      metastatic/invasive potentials derived from a single pancreatic carcinoma cell
      line SUIT-2 showed that the HMTI activity in SFCM was correlated to the degree of
      histological differentiation in vivo and tended to be inversely correlated to
      their metastatic/invasive capabilities. Immunoblotting analysis revealed that
      these HMTI were protease nexin-II/amyloid beta protein precursors (PN-II/APP).
      Semi-quantificative reverse-transcriptase/polymerase-chain reaction study for PN
      II/APP mRNAs suggested that the differences in PN-II/APP activities in SFCM
      between the subclones might be post-transcriptional or post-secretional events.
      In addition, SFCM of a highly metastatic subclone contained 43-kDa protein which
      reacted to anti-APP monoclonal antibody (MAb) suggesting that the subclone may
      have APP-degrading activity.

PMID- 7814145
TI  - Abnormal protein tyrosine kinase gene expression during melanoma progression and
      metastasis.
AB  - Protein tyrosine kinases have been implicated in tumor initiation and
      progression. Here we used Northern blotting to study expression of their genes in
      cultured normal melanocytes and 19 melanoma cell lines from different stages of
      tumor progression. We detected transcripts for 2 cytoplasmic (ABL and FES) and 6
      receptor (ECK, ERB-B2, FGF-R4, IGFI-R, KDR and TIE) kinases but not for receptors
      RET or TRK-A. Genes for ECK, FGF-R4 and TIE were expressed ectopically in
      melanomas (not in normal melanocytes). Similarly, ECK protein was detected by
      immunoblotting in metastatic melanomas but not in normal melanocytes. ECK mRNA
      levels tended to increase again during late melanoma progression. ECK and TIE
      mRNAs were also detected in highly metastatic variant cells but not in the
      corresponding poorly metastatic parental lines. Conversely, FES and KDR gene
      expression was lost in most advanced primary and metastatic melanomas. These
      findings suggest positive and negative roles for specific tyrosine kinases during
      progression.

PMID- 7814143
TI  - The role of indoleamine 2,3-dioxygenase in the anti-tumour activity of human
      interferon-gamma in vivo.
AB  - We have studied the relationship between L-tryptophan metabolism and the response
      to human IFN-gamma in 3 human ovarian cancer xenografts growing in nude mice.
      During IFN-gamma therapy all 3 tumours showed a profound depletion in L
      tryptophan and a corresponding rise in L-kynurenine. The microenvironment
      surrounding the tumours was also depleted of L-tryptophan. The IFN-gamma
      inducible enzyme indoleamine dioxygenase, IDO, was induced in treated tumours.
      While there was a variability in IDO mRNA expression in the different xenografts
      tested, in situ hybridization showed that the gene was induced at all levels of
      the tumour, and not just the periphery. These results show that induction of IDO
      by IFN-gamma in vivo can metabolize L-tryptophan rapidly enough for it to become
      depleted, despite a continued supply of L-tryptophan from the host. The IDO mRNA
      and protein remained induced after the L-tryptophan levels had returned to
      normal, suggesting that the gene may be post-transcriptionally regulated and/or
      the IDO co-factor supply may be limited. Another IFN-gamma-inducible gene,
      tryptophanyl tRNA synthetase, was also induced in the tumour. It is possible that
      this enzyme, which is responsible for synthesizing tryptophanyl tRNA, acts in a
      compensatory manner by allowing protein synthesis to continue despite low free L
      tryptophan concentrations. There was no correlation of the above parameters with
      the anti-tumour response to IFN-gamma, suggesting that other mechanisms must play
      a role. L-tryptophan depletion may be a contributor to a multifactorial growth
      inhibition of tumour cells following IFN-gamma treatment, but cannot on its own
      explain their growth inhibition.

PMID- 7814146
TI  - EGF receptor and p185erbB-2-specific single-chain antibody toxins differ in their
      cell-killing activity on tumor cells expressing both receptor proteins.
AB  - Many human tumors over-express erbB-2 and EGF receptors. The membrane
      localization of these receptor tyrosine kinases make them appropriate targets for
      directed tumor therapy. We have used recombinant DNA technology to produce single
      chain antibody exotoxin A (scFv-ETA) fusion proteins which specifically bind the
      erbB-2 and EGF receptors. The scFv portion is composed of the heavy- and light
      chain variable domains of monoclonal antibodies which recognize the extracellular
      portion of each receptor. We have previously described the anti-tumor activity of
      the bacterially produced scFv(FRP5)-ETA directed to the erbB-2 receptor. In this
      paper we describe the characteristics of scFv(225)-ETA, a protein which binds the
      EGF receptor. The bacterially produced recombinant protein binds to the receptor
      with high affinity and inhibits the in vitro growth of the EGF receptor over
      expressing tumor cell lines A431 and MDA-MB468. Combination treatment with scFv
      (FRP5)-ETA and scFv(225)-ETA led to an additive inhibitory effect on the in vitro
      growth of A431 cells. SKBR3 cells expressing low levels of EGF receptor but high
      levels of p185erbB-2 were not affected by scFv(225)-ETA treatment but were
      sensitive to scFv(FRP5)-ETA. Stimulation of SKBR3 cells and HCII RI#11 mouse
      mammary epithelial cells expressing the human erbB-2 with EGF led to an increase
      in scFv(FRP5)-ETA activity, showing that the EGF-induced activation of erbB-2 can
      potentiate the action of the erbB-2-directed toxin. Treatment of athymic nude
      mice with scFv(FRP5)-ETA and the combination of both scFv-ETA proteins led to the
      transient arrest of growth of established A431 tumors. scFv(225)-ETA treatment
      alone was the most effective, leading to tumor shrinkage during the course of
      treatment, whereas treatment with the parental monoclonal antibody 225 led to
      retarded tumor growth.

PMID- 7814147
TI  - Epitope mapping of a mouse monoclonal anti-MUC2 antibody suggests the existence
      of an immunodominant region in the COOH terminus of the MUC2 tandem-repeat
      sequence.

PMID- 7814148
TI  - Association of transforming growth factor alpha (TGFA) and its precursors with
      malignant change in Barrett's epithelium: biological and clinical variables.
AB  - Adenocarcinomas of the gastro-esophageal junction (GEJ) and those arising in
      Barrett's esophagus (BE) are increasing in the West and have a poorer prognosis
      than distal stomach cancers. This has been attributed mainly to anatomical
      location, but biological factors such as growth-regulatory molecules have been
      implicated. We have investigated the expression of one of these factors, TGF
      alpha, and its precursor prepro TGF alpha in 82 adenocarcinomas of GEJ (32
      resected specimens and 50 biopsies) as well as in 48 BE biopsies without tumor,
      by immunohistochemistry and by Western-blot analysis. TGF alpha staining was
      shown in the cytoplasm and membrane of cells. Western blot confirmed that most
      immunoreactivity was against mature TGF alpha (5.6 kDa), but higher-molecular
      weight bands were also identifiable, suggesting some reactivity with prepro
      protein. TGF alpha expression was more extense and intense in intestinal
      metaplasia and cancer. The tubular histological type of adenocarcinoma was more
      often positive than the signet-ring type. Primary tumors with lymph-node
      metastases also had increased TGF alpha expression. We conclude, therefore, that
      there is differential regulation of the expression of TGF alpha and its
      precursors during esophageal tumorigenesis.

PMID- 7814149
TI  - Prognosis following locally recurrent soft-tissue sarcoma. A staging system based
      on primary and recurrent tumour characteristics.
AB  - We have shown that the clinical growth rate of local recurrence from soft-tissue
      sarcoma could be expressed as a growth-rate index (GRI) which was predictive for
      metastasis, and which was able to identify 2 equal populations of good (80% 2
      year MFS) and poor survivors (33%). We now report the associations between
      characteristics of the primary and GRI, and combine primary and locally recurrent
      tumour characteristics in a staging system. We studied 460 adult patients with
      soft-tissue sarcomas of the extremities and trunk wall who were diagnosed and
      treated between 1964 and 1990, of whom 134 developed local recurrences and 151
      metastases. The association of primary tumour size, histologic malignancy grade,
      depth, spontaneous necrosis, intratumoral vascular invasion and S-phase fraction
      with local recurrence, GRI and metastasis were examined. High GRI was associated
      with primary tumours that were larger, deeper, more malignant, underwent
      spontaneous tumour necrosis, demonstrated intravascular invasion and had a higher
      S-phase fraction. The same factors were also strongly associated with the
      incidence of metastasis. A multivariate analysis found GRI and primary tumour
      necrosis to be the strongest and most significant prognostic factors. GRI and
      tumour necrosis were combined in a staging system that identified groups with
      good survival (79 to 94% 2-year MFS), intermediate survival (61% 2-year MFS) and
      exceptionally poor survival (6% 2-year MFS). These findings validate our earlier
      assertion that high GRI reflects highly malignant tumours. A staging system
      composed of primary tumour necrosis and GRI can identify patients who may be
      suitable candidates for trials of adjuvant chemotherapy.

PMID- 7814150
TI  - The evaluation of screening for gastric cancer in Miyagi Prefecture, Japan: a
      population-based case-control study.
AB  - Although a screening program for gastric cancer, using barium X-ray examination,
      has been carried out widely in Japan for the past 3 decades, there is
      insufficient evidence to confirm its effectiveness in terms of reducing
      mortality. To evaluate the effectiveness of the screening, a population-based
      case-control study was carried out in Miyagi Prefecture, Japan. Case subjects,
      who had died from gastric cancer (198) and control subjects matched in age, sex
      and residence (577) were selected from among members of the National Health
      Insurance. Their screening histories during 5 years before the cases were
      diagnosed were surveyed on the basis of records of the regional cancer registry
      and the cancer-detection center. The odds ratio (OR) of death from gastric cancer
      for the persons who participated in the screening at least once during 5 years
      was 0.41. For those who participated only once during 5 years the OR was 0.43,
      and for those whose last participation was 5 years earlier it was 0.30. Our data
      suggest that screening for gastric cancer at 5-year intervals might reduce
      mortality by 60%, and that the effect might remain for at least 5 years.

PMID- 7814151
TI  - Chromosome abnormalities in benign hyperproliferative disorders of epithelial and
      stromal breast tissue.
AB  - Cytogenetic analysis of short-term cultures from 15 cases of benign proliferative
      breast disease (PBD), 10 diffuse PBD and 5 papillomas, and 15 fibroadenomas of
      the breast revealed clonal chromosome abnormalities in 7 diffuse PBD lesions, 4
      papillomas and 5 fibroadenomas. The remaining 14 cases had a normal female
      chromosome complement. Cytogenetically unrelated abnormal clones were seen in 4
      fibroadenomas and 2 PBDs. A single abnormal clone was found in 9 PBDs and 1
      fibroadenoma. Three clonal abnormalities were seen as recurrent changes in 6
      cases, namely interstitial deletions of 3p with 3p 12-14 as the minimally common
      deleted segment (in 1 papilloma, 1 diffuse PBD with atypia and 1 mixed-pattern
      lesion with both papilloma and atypical diffuse PBD features), r(9)(p24q34) (in 1
      diffuse PBD and 1 fibroadenoma), and del(1)(q12)(again in 1 diffuse PBD and 1
      fibroadenoma). Intriguingly, 6 of the 16 abnormal cases had chromosome changes
      that have been seen repeatedly as primary abnormalities in breast carcinomas:
      der(16)t(1;16)(q10;p10), del(3)(p12p14), and del(1)(q12). We conclude that some
      of the chromosome anomalies frequently found in breast carcinomas are also
      present in PBD and fibroadenomas. These aberrations may be accepted as early,
      neoplasia-relevant mutations. However, they do not seem to be sufficient by
      themselves to unleash a malignant process.

PMID- 7814152
TI  - Bcl-2 expression is associated with lymph node metastasis in human ductal breast
      carcinoma.
AB  - The Bcl-2 proto-oncogene product blocks apoptosis. We retrospectively studied Bcl
      2 expression in 124 primary tumors from patients diagnosed with T1 (2 cm or less)
      breast carcinoma with (T1N1) or without (T1N0) lymph-node metastasis. Bcl-2
      protein was detected by immunohistochemistry on paraffin-embedded tissue
      sections. Multivariate logistic regression modeling was used to estimate
      prevalence odds ratios for lymph-node metastasis. Bcl-2 was widely expressed
      among T1 tumors showing a strong positive relationship with estrogen (ER)- and
      progesterone (PR)-receptor-positive tumors. However, a significant inverse
      correlation was seen between Bcl-2 expression and histological grade, Bcl-2 being
      absent in the majority of T1 undifferentiated tumors (grade-III carcinomas).
      Furthermore, Bcl-2 was more frequently expressed in T1N1 cases (72.2%) than in
      T1N0 specimens (45.7%). The odds for lymph-node metastasis in the Bcl-2-positive
      group was 3.6 times larger than that in the Bcl-2-negative group. The co
      expression of PR significantly modified the effect of Bcl-2 on the odds for lymph
      node metastasis, suggesting the existence of a synergistic interaction between
      the 2 parameters. We studied the percentage of dead cells in primary tumors by in
      situ DNA fragmentation (FDNA), and found an inverse correlation between Bcl-2
      expression and FDNA. This supported the hypothesis that Bcl-2 extends cell
      survival. In conclusion, our study provides evidence that Bcl-2 expression is
      involved in breast-cancer progression, at least in a subset of well
      differentiated and PR-positive tumors.

PMID- 7814153
TI  - Altered intracellular processing and enhanced secretion of procathepsin D in a
      highly deviated rat hepatoma.
AB  - Both freshly-isolated rat hepatocytes and Morris hepatoma 7777 cells synthesized
      cathepsin D as a precursor that was either processed intracellular to smaller
      mature forms or secreted into the medium. The pattern of mature enzyme forms was
      different in the 2 cell types. In addition, the relative amount of precursor
      secreted was much higher for hepatoma cells. Monensin strongly enhanced the
      secretion and also impaired the intracellular transport-linked maturation of
      procathepsin D in hepatocytes, while it markedly inhibited intracellular
      maturation and only slightly increased secretion of the pro-enzyme in hepatoma
      cells. Ammonium chloride influenced the intralysosomal segregation and maturation
      of procathepsin D in hepatocytes but not in hepatoma cells. Our observations
      indicate that (i) the lysosomal segregation of cathepsin D was less efficient and
      its fractional secretion higher in hepatoma cells than in hepatocytes; (ii) in
      the 2 cell types, delivery to lysosomes and processing of procathepsin D were
      differently sensitive to increases in the vacuolar pH.

PMID- 7814154
TI  - Burkitt's lymphoma cells are resistant to programmed cell death in the presence
      of the Epstein-Barr virus latent antigen EBNA-4.
AB  - Group I Epstein-Barr virus (EBV)-positive Burkitt's lymphoma (BL) cells display a
      surface phenotype characteristic of germinal centre B cells and readily undergo
      apoptosis in response to a variety of stimuli, including serum deprivation.
      Activation of EBV latent gene expression has been shown to increase the survival
      of these tumour cells by blocking programmed cell death. To investigate the
      nature of this protection, we assessed the function of the EBV latent EBNA-4 gene
      in a group I lymphoma line, dG75. Group I BL cells induced to undergo apoptosis
      in response to serum starvation were protected in the presence of EBNA-4 protein.
      A possible factor underlying this EBNA-4-associated survival was increased
      expression of the oncoprotein bcl-2, a known repressor of cell death. Together
      these data suggest that EBNA-4 plays an important role in the regulation of
      programmed cell death in BL tumour cells.

PMID- 7814156
TI  - Transformation of human keratinocytes is characterized by quantitative and
      qualitative alterations of the T-16 antigen (Trop-2, MOv-16).
AB  - The regulation of synthesis and post-translational processing of the T-16
      antigen, a human cell-surface glycoprotein of 50 to 60 kDa, was investigated in
      normal and transformed human keratinocytes in vitro. Normal keratinocytes of
      interfollicular and follicular origin were compared with squamous-cell-carcinoma
      lines, spontaneously immortalized keratinocytes, and SV-40 transformed
      keratinocytes. FACS analysis and radio-immunoprecipitation showed that the
      synthesis and expression of T-16 was 3- to 4-fold higher in transformed
      keratinocytes than in their normal counterparts. In normal keratinocytes, no
      quantitative differences were observed among freshly prepared cells, primary
      cultures and sub-cultures. In SDS-PAGE, a single broad band at 50 to 60 kDa was
      observed in normal keratinocytes, whereas 2 bands at 42 and 45 to 55 kDa were
      detected after transformation. Tunicamycin treatment of living cells and
      glycosidase digestion of immunopurified T-16 antigen revealed this molecular
      heterogeneity to be due to different N-glycosylation in normal and transformed
      keratinocytes. In pulse-chase experiments, 2 distinct precursor proteins at 38
      and 42 kDa were detected in transformed keratinocytes, whereas in normal cells
      the 38-kDa signal was dramatically decreased. These findings indicate that
      quantitative and qualitative changes of T-16 mark the transformation process of
      human keratinocytes, showing similar post-translational alterations in all
      transformed populations investigated.

PMID- 7814155
TI  - nmb, a novel gene, is expressed in low-metastatic human melanoma cell lines and
      xenografts.
AB  - From a subtractive cDNA library, we isolated several cDNA clones which showed
      differential expression between highly and lowly metastatic human melanoma cell
      lines. One clone, designated nmb, showed preferential expression in the low
      metastatic cell lines and was chosen for further characterization. Sequence
      analysis revealed that this clone represents a novel gene, encoding a putative
      transmembrane glycoprotein which showed the highest homology to the precursor of
      pMEL17, a melanocyte-specific protein. nmb RNA expression was absent in most
      tumor-cell lines tested and not restricted to the melanocytic lineage.
      Transfection of a partial nmb cDNA into a highly metastatic melanoma cell line
      (BLM) resulted, in 2 of 3 transfectants, in slower subcutaneous tumor growth and,
      in 1 of 3 transfectants, in reduction of the potential for spontaneous metastasis
      in nude mice.

PMID- 7814157
TI  - Hemodynamic profile of a post-infarct ventricular septal defect: left atrial a
      waves rather than v-waves may be a prominent feature.
AB  - The presence of prominent left atrial v-waves following interventricular septal
      rupture in acute myocardial infarction have been reported in the past.
      Hemodynamic profile obtained in one particular case highlighted some of the
      varying aspects of pressure wave, oxygen saturation, and compliance abnormalities
      that may also be present in such cases. The presence of large left atrial a-waves
      rather than v-waves was one of the findings.

PMID- 7814158
TI  - Effects of the administration of captopril, metoprolol and of the captopril
      metoprolol combination as adjuvant therapy during thrombolysis in acute
      myocardial infarction.
AB  - The aim of the study was to verify, during thrombolysis in patients with anterior
      acute myocardial infarction, the safety and effects of beta-blockers or ACE
      inhibitors and their combination in the short and long term. One-hundred sixty
      six patients hospitalized within 4 h from the onset of the symptoms (first
      episode), eligible for thrombolysis, Killip class I-II, were randomized (single
      blind) into four groups. Group A (42 patients) received 6.25 mg captopril
      (orally) 15 min before thrombolysis and metoprolol (i.v.) not later than 1 h, and
      orally afterwards. Group B (42 patients) received 6.25 mg captopril 15 min before
      thrombolysis. Group C (37 patients) received metoprolol not later than 1 h. Group
      D (45 patients) received thrombolysis only. Later (day 3), groups C and D also
      received captopril. We checked ventricular arrhythmias (first 2h) from
      thrombolysis, creatine kinase peak, creatine kinase peak normalization time, late
      ventricular arrhythmias at Holter test pre-discharge (Lown's class > 2). At
      follow-up (mean 30.5 +/- 2 months), mortality was evaluated for reinfarction and
      ventricular failure. Age and sex were similar. RESULTS: Early ventricular
      arrhythmias: Group A, five cases; Group B, five cases; Group C, 15 cases; Group
      D, 16 cases. Creatine kinase peak: Group A, 1875 +/- 220 U/l; Group B, 1566 +/-
      168 U/l; Group C, 2274 +/- 212 U/l; Group D 2103 +/- 232 U/l. Creatine kinase
      peak normalization time: Group A, 57.7 +/- 3 h; Group B, 58.1 +/- 3 h; Group C,
      72.7 +/- 3 h; Group D, 69.5 +/- 2 h (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7814159
TI  - Clinical profile and natural history of Ebstein's anomaly of tricuspid valve.
AB  - There were 63 patients of Ebstein's anomaly of tricuspid valve encountered from
      1976 to 1991; 28 (44.4%) were male and 35 (55.6%) female. Their age at
      presentation ranged from 3 months to 51 years. Five (7.9%) patients were
      asymptomatic, 48 (76.2%) had class II-III exertional dyspnoea, palpitation or
      both. Thirty patients (47.6%) had cyanosis. Electrocardiogram showed paroxysmal
      atrial fibrillation in two, chronic atrial fibrillation in four (6.3%),
      paroxysmal supraventricular tachycardia in seven, atrial or ventricular ectopic
      beats in five (7.9%), 2:1 atrioventricular block in one (1.6%), complete
      atrioventricular block in two (3.2%) and type B WPW syndrome in nine patients
      (14.3%). Chest X-ray showed diminished vascularity in 22 (34.9%). Diagnosis was
      established by cardiac catheterization and or echocardiography. Atrialized right
      ventricular chamber was demonstrated in 51 (80.9%) by angiography and in 40
      (63.5%) by electrophysiology. Patients were followed up for 1-172 months.
      Seventeen patients (26.9%) required surgery. Three patients (4.8%) died during
      medical follow-up, and five (7.9%) died following surgery. Survival probability
      for 46 medical patients was 88.9% at 172 months. Factors affecting survival were
      pulmonary blood flow, cyanosis, clubbing and systemic arterial oxygen saturation.

PMID- 7814160
TI  - Late potentials, QTc prolongation, and prediction of arrhythmic events after
      myocardial infarction.
AB  - In a series of 171 consecutive survivors of acute myocardial infarction, the
      predictive value of late potentials and QTc prolongation was prospectively
      assessed. QT intervals were measured in lead V2, corrected QT (QTc) was
      calculated using Bazett's equation (cut-off value 440 ms). Late potentials were
      considered to be present when all of the three signal-averaged
      electrocardiographic variables were abnormal (i.e. QRS > 114 ms, D40 > 38 ms, and
      V40 < 20 microV). Complete follow-up was obtained (mean 13 +/- 6 months, range 6
      24 months). Six percent of the patients had an arrhythmic event (i.e. sustained
      ventricular tachycardia or sudden death). The relative risk of late potentials
      for arrhythmic events was 7.7 (P < 0.02). The relative risk of QTc > 440 ms was
      1.1 (NS). In a multivariate analysis, the addition of QTc prolongation did not
      significantly improve the prognostic value of late potentials alone. It is
      concluded that late potentials are predictive of arrhythmic events after
      myocardial infarction, but the presence of concomitant QTc prolongation does not
      worsen the prognosis.

PMID- 7814162
TI  - Prevalence of coronary heart disease and cardiovascular risk factors in middle
      aged males in a defined population in central Sri Lanka.
AB  - In a cross-sectional survey, we estimated the prevalence of coronary heart
      disease in a sample of 975 middle-aged males (35-59 years), from a defined
      population in the Central province of Sri Lanka using the London School of
      Hygiene cardiovascular questionnaire and a 12-lead electrocardiogram. The
      estimated prevalence rates were: (a) Definitive evidence of ischemic heart
      disease (positive symptoms and ECG changes of ischemia), 16/1000 (95% C.L., 9
      27). (b) Evidence of coronary heart disease based on history alone 54/1000 (95%
      C.L., 40-71). (c) Estimate based on ECG changes of ischemia without symptoms
      32/1000 (95% C.L., 21-46). Median values for major risk factors were: systolic
      blood pressure 120 mmHg, diastolic blood pressure 88 mmHg, serum cholesterol 4.99
      mmol/l, high density lipoproteins 0.99 mmol/l and body-mass index 20.4 kg/m2.
      About half (57.9%) the subjects were current smokers, 17% had actual hypertension
      (systolic blood pressure > 159 mmHg and/or diastolic blood pressure > 94 mmHg
      and/or been treated for hypertension), 12.6% had hypercholesterolemia (serum
      cholesterol levels > 6.5 mmol/l), 18.4% had a body-mass index > 24 kg/m2 and 5.8%
      were diabetic. Hypercholesterolemia (> 6.5 mmol/l), a higher body-mass index (>
      24 kg/m2) and diabetes were more prevalent among subjects living in an urban
      rather than a rural environment.

PMID- 7814161
TI  - Physiological pacing improves symptoms and increases exercise capacity in the
      elderly patient.
AB  - We evaluated the benefits of physiological pacing in the elderly by recruiting 13
      subjects > 75 years of age, already fitted with a physiological pacing system.
      All had been paced for complete or Mobitz II heart block. Double blind cross over
      study was performed comparing exercise capacity, measuring distance walked on a 6
      min walking test and time taken to climb two flights of stairs; and symptoms,
      evaluated by an activity of daily living questionnaire, in atrioventricular
      synchronous and ventricular pacing. Mean distance walked was significantly higher
      in atrioventricular synchronous than in ventricular pacing (360 +/- 65 m vs. 327
      +/- 69 m; P < 0.01). No significant difference was found in the ability to climb
      stairs but there was a marked improvement in the symptomatic questionnaire score,
      19 +/- 5 in physiological pacing increasing to 28 +/- 10 with ventricular.
      Physiological pacing in the elderly produces an increase in exercise tolerance
      and improves symptoms; therefore, age alone should not be a contraindication to a
      physiological system.

PMID- 7814163
TI  - Plasma levels of apolipoproteins A-1 and B in Indian patients with
      angiographically defined coronary artery disease.
AB  - Apolipoproteins A-1 and B concentration were measured in 201 Indian patients (32
      females; 169 males) undergoing elective diagnostic coronary arteriography in
      order to assess the predictive power of apolipoproteins as a 'marker' of coronary
      artery disease (CAD). This association was also compared to that of other
      traditional risk factors: age, hypertension, diabetes, family history, smoking
      and plasma levels of total cholesterol, triglycerides, low and high density
      lipoproteins. The apolipoprotein (Apo) A-1 levels averaged 82.9 +/- 18.9 mg/dl in
      the normal coronary group (n = 43) and 76.0 +/- 18.1 mg/dl in the group with
      coronary artery disease (n = 158). The average Apo B levels in the normal
      coronary group and coronary artery disease group were 67.8 +/- 17.7 mg/dl and
      78.9 +/- 19.5 mg/dl, respectively. Overall Apo B and triglyceride levels (of all
      lipid measures) showed larger univariate difference between the normal group (no
      coronary artery disease) and the group with coronary artery disease. The variable
      with strongest predictive power for coronary artery disease was the ratio of Apo
      A-1 to Apo B. These findings were confirmed using multiple logistic regression
      analysis adjusting for age and other traditional risk factors. Our results
      indicate that the measurement of apolipoproteins A-1 and B provide a better
      marker for predicting the presence of coronary artery disease as compared to
      traditional lipid measures. Overall the levels of these apolipoproteins seem to
      be lower in Indian population as compared to those reported from the West.

PMID- 7814164
TI  - Comparison of ambulatory blood pressure monitoring and conventional office
      measurement in the workers of a chemical company.
AB  - The aim of the present study was to define the different prevalence of
      hypertension when conventional office measurement and ambulatory monitoring are
      performed in a population of unselected workers. All the workers of a Florentine
      chemical company were invited to participate in the study. Enrolled subjects
      underwent blood pressure measurement using a conventional sphygmomanometer and
      ambulatory blood pressure monitoring. Of 191 workers, 145 agreed to participate
      in the study (76%). Six of the 145 were excluded from further analysis because
      they were undergoing antihypertensive therapy. Confidence limits for ambulatory
      monitoring were defined at 95% on normotensive workers. Thirty-five (25%) workers
      were found to be hypertensive according to World Health Organization parameters
      (diastolic pressure > 90 mmHg) but only 14 of the 35 had higher 24-h diastolic
      ambulatory blood pressure than the 95% confidence limits of controls.

PMID- 7814166
TI  - Intracardiac thrombi in both the right atrium and right ventricle after acute
      inferior-wall myocardial infarction.
AB  - We present a case of inferior-wall myocardial infarction associated with thrombi
      in both the right ventricle and right atrium. Routine transthoracic
      echocardiography could not detect these thrombi while transesophageal
      echocardiography provided an excellent image of the thrombi. The right atrium or
      right ventricle may be the site for thrombi, presumably due to both right
      ventricular and right atrial infarction in acute inferior-wall infarction.

PMID- 7814165
TI  - Serial evaluation of dilated cardiomyopathy with exercise thallium-201
      tomography: correlation with the evolution of left ventricular parameters.
AB  - The purpose of this prospective study was to correlate (1) the initial findings
      of exercise thallium-201 tomography with the evolution of left ventricular
      parameters at long term follow-up in patients with dilated cardiomyopathy and (2)
      the changes of exercise thallium-201 tomography repeated 1 year later. We studied
      19 men with dilated cardiomyopathy and normal coronary angiogram. Two patients
      died and three patients had heart transplantation during follow-up. The other 14
      patients were assessed at baseline and 1-year follow-up. Thallium-201 tomograms
      were divided into 20 segments for each patient. Two groups were defined according
      to the evolution of left ventricular ejection fraction: group 1 (n = 7) had
      unchanged or decreased ejection fraction at follow-up (24 +/- 11% at baseline
      versus 22 +/- 11% at follow-up, ns) and group 2 (n = 7) had improved ejection
      fraction at follow-up (25 +/- 9% at baseline versus 49 +/- 8% at follow-up, P <
      0.03). The number of total abnormal segments at stress were not statistically
      different at baseline between groups 1 and 2, and in group 1 between baseline and
      follow-up. Group 2 at follow-up had a reduced number of total abnormal segments
      (P < 0.03). The percentage of reversibility was similar in both groups at
      baseline and follow-up. On exercise thallium-201 tomography, neither the presence
      nor the reversibility of stress myocardial perfusion abnormalities can predict
      improvement of left ventricular ejection fraction in dilated cardiomyopathy.
      However, regression of dilated cardiomyopathy is accompanied by a reduction of
      stress myocardial perfusion abnormalities.

PMID- 7814167
TI  - Multiple anomalies of caval veins in a patient with pulmonic stenosis.
AB  - Anomalies of the supra-diaphragmatic portion of the inferior caval vein are rare
      in patients with normal sinus. We recently encountered a patient with situs
      solitus and infundibular pulmonic stenosis who had bifurcation of the supra
      diaphramatic portion of the inferior caval vein with anomalous high insertion of
      one portion into the mid-right atrium. The other division joined the coronary
      sinus which also received a persistent left superior caval vein and left hepatic
      veins. Biplane angiography was used to delineate the anatomy. Pre-operative
      delineation is required as this anomaly complicates cardio-pulmonary bypass.

PMID- 7814168
TI  - Outcome of patients with diabetes and unstable angina. A subgroup analysis in the
      Spanish Multicentre Trial of trifusal in unstable angina. Grupo de Estudio del
      Trifusal en la Angina Inestable.
AB  - We analyzed the clinical characteristics of the 58 diabetic and 218 nondiabetic
      patients enrolled in the Spanish multicentre trial of trifusal in unstable
      angina. After 6 months of follow-up, 25 suffered from myocardial infarction or
      death, 10 of which were diabetics (17.2%) and 15 nondiabetics (6.9%) (P =
      0.0146). This difference remained significant after multivariate analysis. We
      conclude that diabetes is an independent predictor of adverse outcome in patients
      with medically treated unstable angina.

PMID- 7814169
TI  - Balloon dilatation of supravalvular aortic stenosis: a report of two cases.
AB  - Balloon dilatation was performed in two cases of supravalvular aortic stenosis
      with variable results. There was remarkable reduction in gradient in the patient
      with membranous obstruction and the benefits are sustained at 18 months follow
      up. The patient with hour-glass obstruction had only a partial success with
      reappearance of obstruction within 1 week. Balloon dilatation may emerge as a
      viable treatment modality for membranous obstructions. However, a large study is
      needed to establish the place of this procedure.

PMID- 7814170
TI  - Spontaneous hepatic hemorrhage following treatment with tissue plasminogen
      activator.

PMID- 7814171
TI  - Echocardiographic detection of right ventricular segmental wall motion
      abnormalities in rheumatic mitral valve disease.

PMID- 7814172
TI  - Use of unexplained acronyms in specialty journals.

PMID- 7814173
TI  - Autogenous arterial grafts for coronary bypass surgery: current status and future
      perspectives.

PMID- 7814174
TI  - Dietary lactose as a possible risk factor for ischaemic heart disease: review of
      epidemiology.
AB  - International data show stronger correlations of mortality from ischaemic heart
      disease with per capita supply of dairy products excluding fat than with dairy
      fat, and of estimated lactose than with dairy fat or margarine and other
      processed fats (positively) and vegetable oils and fats, fat of fish or wine
      (negatively). Butter and cheese, which have a low content of lactose, show
      moderate and zero correlations, respectively. Populations with low or
      intermediate prevalence of adult lactose absorbers have a lower supply of dairy
      products excluding butter (and therefore of lactose), and a lower mortality from
      ischaemic heart disease, than populations with a high prevalence of absorbers.
      Specific national and ethnic data suggest that a diet low or relatively low in
      lactose, in populations with low or relatively low prevalence of lactose
      absorbers, is more consistently associated with protection against ischaemic
      heart disease than are high intakes of unsaturated fatty acids, wine, alcohol or
      dietary fibre. In seven countries with a high consumption of dairy products (six
      at least with a high prevalence of lactose absorbers), trends in ischaemic heart
      disease mortality appear to have reflected changes in the supply of milk (and
      therefore of lactose), but not consistently of butter or inversely of unsaturated
      fatty acids. The findings reviewed in this paper call for further investigation
      of the subject, epidemiologically and biochemically.

PMID- 7814175
TI  - Response of patients with coronary artery disease stratified by ejection fraction
      following short-term training.
AB  - The purpose of this study was to investigate the response of patients with
      ischemic heart disease and varied left ventricular function following 6 weeks of
      exercise training. We studied the oxygen consumption (VO2), and central
      hemodynamic and metabolic responses of 14 patients with coronary artery disease
      (CAD) stratified by left ventricular ejection fraction (EF). There were two
      groups of patients: normal EF (NEF), EF = 64 +/- 9.9 (mean +/- S.E.M.); n = 7,
      and diminished EF (DEF), EF = 36 +/- 11.6; n = 7. The patients ranged in age from
      42 to 72 years (54.9 +/- 2.2), and were evaluated prior to and then following
      training. Measures of VO2, cardiac output (Qt) stroke volume (SV), heart rate
      (HR), exercise duration (XTIME) and intensity (XI), as well as plasma lactate
      (LA), and the catecholamines epinephrine (E) and norepinephrine (NE) were
      obtained in response to maximal cycle ergometry. Subjects trained three times per
      week, 30 min per session, at an intensity equal to 70% of their peak oxygen
      consumption. Repeated measures analysis of variance (ANOVA) revealed no
      interaction between groups suggesting a similar training response. Significant
      post-training changes (P < 0.05) were observed in peak VO2 (VO2peak) NEF, 11.8%
      increase, (16.0 +/- 1.3 to 17.9 +/- 1.1 ml/kg/min) and DEF, 9.3% increase (15.1
      +/- 1.6 to 16.5 +/- 1.2 ml/kg/min); submaximal HR, 4% decrease in the NEF (95.57
      +/- 4.58 to 92 +/- 4.43 beats/min) and a 6% decrease in the DEF (107.29 +/- 7.44
      to 101.43 +/- 6.77 beats/min); XTIME NEF, 11.2% increase (7.8 +/- 0.57 to 8.67 +/
      0.61 min) and DEF, 16.6% increase (7.3 +/- 0.91 to 8.51 +/- 0.69 min); and XI
      NEF, 19.2% increase (104.3 +/- 11.3 to 124.3 +/- 12.9 W) DEF, 21.2% increase
      (94.3 +/- 18.5 to 114.3 +/- 16.9 W), and a 15% decrease in resting NE (350 +/- 26
      to 296.9 +/- 19 pg/ml). There were no changes in Qt, SV, LA, E, peak NE or peak
      HR for either group. These findings suggest short-term endurance training at 70%
      VO2peak provide the necessary stimulus for individuals with CAD and NEF or DEF to
      display an improvement in XI, XTIME, and VO2peak. The lack of a significant
      enhancement in Qt with short-term training may indicate that the mechanism by
      which both study groups were able to attain significantly higher levels of
      VO2peak may have been attributable to peripheral mechanisms rather than any
      alterations in Qt, a central mechanism.

PMID- 7814176
TI  - Percutaneous transvenous mitral commissurotomy in 390 cases using the Inoue
      balloon catheter.
AB  - Percutaneous transvenous mitral commissurotomy using the Inoue technique was
      performed in 390 cases of rheumatic mitral stenosis. There were 220 (56%) females
      and 170 (44%) males. The age range was 9-47 years [mean +/- S.D., 26 +/- 14) and
      all were symptomatic (New York Heart Association (NYHA) class II in 23 (6%);
      class III in 280 (72%); and class IV in 87 (22%) patients]. Mitral valve area
      increased from 0.6 +/- 0.4 to 2 +/- 0.7 cm2, mean transmitral gradients decreased
      from 26 +/- 8 to 5 +/- 3 mmHg and cardiac index improved from 2.2 +/- 0.8 to 3.0
      +/- 0.7 l/min/m2 (P < 0.001). There were no procedure related deaths. An increase
      in mitral regurgitation by one grade was observed in 40 (10%) cases, with 8 (2%)
      cases developing severe mitral regurgitation. Oximetry evidence of left to right
      atrial shunt (Qp/Qs > or = 1.5:1) was observed in 11 (3%) patients. Four (1.0%)
      patients developed cardiac tamponade, none had thromboembolism. Follow-up of 290
      cases at 26 +/- 5 weeks showed persistent improvement in clinical (NYHA class I
      in 98%) and echocardiographic mitral valve area. Percutaneous transvenous mitral
      commissurotomy is safe, easy to perform and provides excellent clinical and
      hemodynamic benefit in the majority of cases.

PMID- 7814177
TI  - Circadian variations of atrial natriuretic peptide in normal people and its
      relationship to arterial blood pressure, plasma renin activity and aldosterone
      level.
AB  - To investigate the circadian variations of plasma atrial natriuretic peptide
      (ANP) and its relationship to arterial blood pressure, plasma renin activity and
      aldosterone level, we determined 24-h blood pressure in 14 healthy volunteers.
      Plasma ANP concentration, renin activity and aldosterone levels were measured
      every 3 h by radioimmunoassay. We found no significant circadian variation of
      plasma ANP level (pg/ml) (daytime level, 62 +/- 24 vs. nighttime level, 57 +/-
      19, P = 0.146) and plasma renin level (ng/ml/h) (1.32 +/- 0.78 vs. 1.15 +/- 0.57,
      P = 0.148), but there was diurnal change of blood pressure (mmHg) (systolic, 122
      +/- 7 vs. 116 +/- 11, P < 0.001; diastolic, 80 +/- 11 vs. 72 +/- 11, P = 0.025)
      and plasma aldosterone level (pg/ml) (86 +/- 42 vs. 62 +/- 37, P < 0.001). The
      blood pressure and aldosterone levels reached maxima (11:00 h and 08:00 h,
      respectively) before that of ANP (17:00 h) and then decreased together until the
      nadir at 02:00 h. This might indicate that elevation of arterial blood pressure
      and plasma aldosterone level stimulate release of ANP under normal physiological
      conditions.

PMID- 7814178
TI  - Electrophysiologic in-vitro effects of cocaine and its metabolites.
AB  - We studied the in-vitro electrophysiologic effects of equimolar concentrations of
      cocaine and its metabolites on rat cardiac tissues. The effects on the sinus node
      rate were studied in spontaneously active sinoatrial preparations. The order of
      magnitude of the effects was: ethylcocaine > cocaine > benzoylecgonine and
      ecgonine methyl ester > ecgonine. The effects of cocaine and ethylcocaine were
      not additive. The actions of cocaine and ethylcocaine on membrane potentials were
      studied in papillary muscles driven at 5 Hz. Both compounds depressed to similar
      degrees the resting potential and the amplitude of the action potential, and
      increased the duration of the action potential. Simultaneous exposure to the two
      drugs did not result in effects greater than those of ethylcocaine or cocaine
      alone. It is concluded that (a) cocaine and its metabolites depressed the sinus
      node rate. Only cocaine and ethylcocaine exerted actions that may be of clinical
      significance. (b) Ethylcocaine had an effect greater than that of cocaine on the
      sinus node rate, and similar to that of the parent compound on ventricular
      membrane potentials. Thus, ethylcocaine may play a significant role in the
      cardiac electrophysiologic actions of cocaine, when the latter is used in
      combination with ethanol. (c) The effects of cocaine and ethylcocaine were not
      additive.

PMID- 7814179
TI  - Radiofrequency ablation of fascicular tachycardia: efficacy of pace-mapping and
      implications on tachycardia origin.
AB  - Verapamil-sensitive but adenosine resistant left ventricular tachycardia
      (fascicular tachycardia) is a recognised cause of ventricular tachycardia
      occurring in patients without overt cardiac disease. This study addresses (1) the
      efficacy of radiofrequency ablation guided by pace-mapping technique in the
      treatment of this tachycardia, and (2) the location of this tachycardia in the
      left ventricle as assessed by simultaneous ventriculography. Five patients (two
      women and three men, mean age 25 +/- 8 years) with ventricular tachycardia
      exhibiting a right bundle branch block and left axis deviation morphology, with
      documented response to verapamil but resistance to intravenous adenosine
      triphosphate were studied. Biplane left ventricular cineangiography was first
      performed to visualise the topography of the left ventricle. Pace-mapping at a
      rate within 10 beats/min of the tachycardia rate was performed, and the
      concordance of paced QRS configuration with that of the induced tachycardia was
      compared for each of the 12 leads for major or minor differences. A perfect pace
      map could be achieved in all five patients (two in posteroseptal left ventricle
      and three in the posterior left ventricular wall). Five of eight applications at
      an identical pace-map resulted in suppression of tachycardia induction, whereas
      none of the 39 applications at sites with a less identical map was successful (P
      < 0.001). After a successful procedure, there was no recurrence as assessed
      clinically, by non-invasive monitoring (event recording, Holter monitoring and
      exercise testing for all patients) and repeat electrophysiology testing (three
      patients) during a follow-up of 12 +/- 3 months. Thus radiofrequency ablation
      guided by pace-mapping technique is a highly efficacious treatment for fascicular
      tachycardia. The response to radiofrequency ablation suggests the origin of
      tachycardia as reentry circuits involving the lower septum or posterior part of
      the left ventricle close to or within the endocardial surface.

PMID- 7814180
TI  - Evaluation of the reliability of ST segment monitoring by transtelephonic
      electrocardiogram transmission.
AB  - INTRODUCTION: Transtelephonic electrocardiographic transmission is a diagnostic
      technique which has been systematically applied in recent years, mainly for the
      detection of arrhythmias or pacemaker malfunction. The purpose of this study was
      to assess the efficacy of this method in the recording and transmission of ST
      segment and T wave changes. METHOD: A Bruce protocol exercise stress test was
      carried out in 47 consecutive patients (39 males, eight females, age 53.1 +/-
      11.5 years) with suspected coronary artery disease (CAD). At the same time, a
      transtelephonic ECG system, with a 2-min memory and the capability for 16.5 days
      continuous recording, was used to transmit the ECG (modified leads II and V5).
      RESULTS: A positive ST segment shift was observed in 19 patients (40.4%) during
      the exercise test. The transtelephonic system recorded this change in 18 of these
      patients but missed the anteroseptal ST segment depression (V2-V4) in one patient
      (sensitivity 94.7%). All of the 23 patients with no ST segment changes during the
      exercise test had a negative transtelephonic ECG transmission (specificity 100%).
      The width of the ST depression recorded from modified lead II on the
      transtelephonic recording was not significantly different from that of the 12
      lead ECG. The same was true for modified lead V5. CONCLUSION: Transtelephonic ECG
      transmission in patients with suspected CAD can significantly contribute to the
      investigation of this problem, since the method has high sensitivity and
      specificity. The capacity for continuous recording and the memory of the device
      make possible the monitoring of high risk patients for a good length of time.

PMID- 7814181
TI  - Use of the gastro-oesophageal route for the rapid establishment of ventricular
      pacing.
AB  - A novel approach to emergency ventricular pacing has been developed using a
      gastro-esophageal electrode. The polythene electrode was passed into the stomach,
      after which the electrode tip was positioned in the gastric fundus. Ventricular
      pacing was performed using a cathode mounted on the electrode tip; the
      indifferent electrode (anode) was either a chest pad or a proximal ring
      electrode. Ventricular capture was easily achieved in three emergency cases of
      severe bradyarrhythmia.

PMID- 7814182
TI  - High-grade atrioventricular block during dipyridamole stress testing.
AB  - Dipyridamole stress testing may be used in the diagnosis of coronary artery
      disease and risk assessment of patients who are unable to exercise. Although
      dipyridamole perfusion imaging has a good safety record, serious side-effects may
      rarely occur. We present a case in which dipyridamole induced high-grade
      atrioventricular (AV) block that responded promptly to intravenous aminophylline
      but not to atropine.

PMID- 7814183
TI  - Transient myocardial injury after elective electrical cardioversion.
AB  - A patient with recent myocardial infarction underwent elective direct current
      countershock because of atrial fibrillation. After several shocks, the ST
      segments were strikingly raised throughout the precordial leads, which
      disappeared with the administration of a perfusion of nitroglycerin. This case is
      evidence that electrical cardioversion can cause myocardial damage.

PMID- 7814184
TI  - Cardiac arrest in a 31-year-old man because of the Arnold-Chiari malformation.
AB  - We describe a 31-year-old man who suffered from loss of consciousness and cardiac
      arrest with ventricular fibrillation after a brisk head movement. Clinical
      investigation was inconclusive apart from the magnetic, resonance imaging that
      showed the Arnold-Chiari malformation. It must be taken into account in the
      diagnosis, as a specific treatment is possible.

PMID- 7814185
TI  - Transient myocardial dysfunction in a patient with subarachnoid haemorrhage.
AB  - We report a patient of subarachnoid haemorrhage who presented with severe left
      ventricular dysfunction and marked electrocardiographic changes indistinguishable
      from acute myocardial infarction. Coronary arteriography showed normal anatomy
      and the ventricular regional wall motion abnormalities recovered spontaneously
      after 3 weeks. The implications of this association are discussed.

PMID- 7814186
TI  - Torsades de pointes ventricular tachycardia following right pneumonectomy:
      insights into the relation between right cardiac sympathetic nerve damage, QT
      intervals, and arrhythmias.
AB  - Polymorphic ventricular tachycardia in association with prolongation of the QT
      interval on the surface electrocardiogram (ECG) has long been recognized as an
      important cause of life threatening arrhythmias that can occur with congenital or
      acquired abnormalities of cardiac repolarization. One hypothesis of the origin of
      these arrhythmias states that overactivity of the left-sided sympathetic or under
      activity of the right-sided sympathetic neural input to the heart leads to
      prolonged repolarization and ventricular arrhythmias. This hypothesis has led to
      the application of left cervicothoracic sympathetectomy for control of
      arrhythmias in congenital long QT syndromes. Although animal models have shown QT
      prolongation following right stellate ganglionic section or left stellate
      stimulation, spontaneous ventricular arrhythmias following stellate stimulation
      or block in man have not been demonstrated. We report the case of a patient with
      life threatening ventricular arrhythmias following surgical damage to the right
      cardiothoracic sympathetic nerves.

PMID- 7814187
TI  - Unruptured aneurysm of the left sinus of Valsalva presenting with atrial
      fibrillation.
AB  - Congenital aneurysms arising from the left sinus of Valsalva are extremely
      uncommon, and when unruptured often asymptomatic. Abnormalities of rhythm are
      more commonly associated with dilatation of the right coronary sinus although the
      reason for this is unclear. We report the first case of an unruptured aneurysm
      involving the left sinus of Valsalva presenting with paroxysmal atrial
      fibrillation. Two-dimensional echocardiography confirmed the diagnosis.

PMID- 7814188
TI  - Transient hepatic dysfunction in two brothers receiving heparin and
      streptokinase: a genetic predisposition?
AB  - Two brothers with acute myocardial infarction are presented. Subsequent to a
      standard thrombolysis treatment with streptokinase and heparin, both developed
      abnormal liver tests, with elevated transaminases only. This liver dysfunction
      resolved promptly. The occurrence of such side-effects in two siblings raises the
      question of genetic predisposition to the otherwise uncommon hepatic
      complications of thrombolysis treatment.

PMID- 7814189
TI  - The influence of grade on the outcome of stage I ovarian immature (malignant)
      teratomas and the reproducibility of grading.
AB  - An analysis of 244 immature teratomas (IT) was undertaken to evaluate the
      clinical usefulness and reproducibility of the grading system. Clinical follow-up
      was available for 143 stage I tumors and ranged from 7 to 204 months (mean 85
      months, median 84). Sixteen of 91 (18%) patients with high-grade teratomas were
      dead with metastases. These results are much improved over the years before the
      use of modern (1970 or later) combination chemotherapy. In contrast, only 3 of 52
      (6%) patients with grade 1 tumors died, 1 of whom was living with tumor 6 years
      after surgery. None of the three neoplasms was adequately sampled. Of the three
      grade 1 tumors that progressed, the smallest one weighed > 1,500 g and the other
      two were huge; yet, only one to five slides per tumor were available for review.
      The study confirmed that small foci (2 mm or less) of other germ cell elements do
      not adversely affect the prognosis of IT. The reproducibility between
      pathologists of the traditional grading system for IT, based on the amount of
      immature neuroepithelium, is only moderate if a three-tiered scale is used and
      limited by the results of the least skilled observer (kappa = 0.54). Although
      never approaching complete agreement, interobserver variability is reduced if a
      two-tiered system is used (kappa = 0.66). Microscopic patterns that were the
      source of disagreement were identified. Agreement could be improved with training
      sessions.

PMID- 7814190
TI  - Endometrioid carcinoma of the ovary and endometrium, oxyphilic cell type: a
      report of nine cases.
AB  - Six endometrioid carcinomas of the ovary and three of the endometrium composed
      predominantly or entirely of large eosinophilic (oxyphilic) cells are reported.
      The ovarian tumors occurred in women 31-75 years of age, with a mean of 58 years,
      and the endometrial tumors occurred in women 37-50 years, with a mean of 44
      years. All the ovarian tumors and one endometrial tumor contained focal areas
      typical of endometrioid carcinoma, with round to oval tubular glands lined by
      simple or stratified columnar cells and focal squamous differentiation. Two
      endometrial tumors were composed almost exclusively of oxyphilic cells lining
      glands. One endometrial tumor contained prominent luminal and intracytoplasmic
      mucin. Five of the ovarian tumors were grade 2/3 and one was grade 3/3, whereas
      two of the endometrial tumors were grade 1/3 and one was grade 2/3. The
      prominence of the oxyphilic cells posed diagnostic difficulty in most of the
      cases. Electron microscopic examination performed on all tumors showed abundant
      mitochondria in only one, an ovarian tumor. Other organelles, especially
      microfilaments and tonofibrils, are cited as other possible reasons for the
      eosinophilia. Four of the nine cases were recent; follow-up of the remaining five
      showed a biological behavior similar to the typical endometrioid carcinoma of the
      ovary and endometrium. We suggest that the diagnosis of "endometrioid carcinoma,
      oxyphilic cell type" is appropriate for this variant of carcinoma largely
      composed of eosinophilic cells that may or may not be "oncocytic" in nature. The
      importance of recognizing this entity lies in distinguishing it from diverse
      other primary and metastatic oxyphilic cell tumors of the ovary and eosinophilic
      cell metaplasia and rare other types of primary carcinoma with eosinophilic cells
      of the endometrium, which may be especially challenging in a curettage or biopsy
      specimen.

PMID- 7814191
TI  - Luteinized adult granulosa cell tumors of the ovary: a report of four cases.
AB  - Four luteinized adult granulosa cell tumors of the ovary in women 22-76 (average
      53) years of age are described. Two patients presented with postmenopausal
      bleeding, one with dysfunctional uterine bleeding and one with amenorrhea. The
      tumors were all stage Ia, ranged from 2 to 11 (average 5.1) cm in greatest
      dimension, and were typically solid, lobulated, and yellow. On microscopic
      examination the most striking feature was the abundant eosinophilic cytoplasm of
      most of the tumor cells, which resembled the granulosa cells of the corpus
      luteum. The tumor cells typically grew diffusely, but large nodules intersected
      by scanty fibrous septa were present in all the cases. Additional patterns
      present focally included cords or ribbons, nests, and thick trabeculae. The
      tumors had inconspicuous amounts of fibrothecomatous stroma; foci of stromal
      edema or myxoid change were present in three cases. The tumor cell nuclei were
      round, of moderate size, and pale, and many of them had nuclear grooves. There
      was no significant nuclear pleomorphism and the mitotic rate did not exceed 1 per
      10 high power fields. Reticulum stains, available in three cases, confirmed the
      granulosa cell nature of the neoplasms by disclosing scanty intercellular fibrils
      in most areas. Immunostains, performed in two cases, showed positivity for
      vimentin in both of them and for cytokeratin, smooth-muscle actin, and S-100 in
      one. One tumor from a 75-year-old woman was associated with an ectopic decidual
      reaction in a periovarian adhesion. This patient had focal, severe atypical
      complex hyperplasia of the endometrium and focal secretory change in the
      endometrium uninvolved by the hyperplasia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7814192
TI  - Alteration of p53 in ovarian cancer: its occurrence and maintenance in tumor
      progression.
AB  - Fifty cancers, seven borderline tumors, and two adenomas of the ovary were
      immunohistochemically examined for alteration of p53 to clarify its clinical
      significance. Nuclear accumulation of p53 protein was detected in 60% of the
      cancers, but in none of the borderline tumors or adenomas. No significant
      correlation was found between aberrant expression of p53 and clinical stage or
      histological type. DNA aneuploidy was significantly more common and the Ki-67
      index was significantly higher in the cancers with altered p53 protein than in
      those without it. There was a concordant expression level of p53 in primary and
      matched metastatic lesions in all twelve pairs of cancers examined. These
      findings suggest that alteration of p53 protein is an event that occurs in the
      development of cancer, but not of borderline tumors of the ovary, and that it
      occurs before metastasis and remains unchanged thereafter.

PMID- 7814193
TI  - Characterisation of complex carbohydrates in cervical glandular intraepithelial
      neoplasia and invasive adenocarcinoma.
AB  - Using a panel of 11 biotinylated lectins and an avidin-peroxidase detection
      system on paraffin sections of formalin-fixed material, the range of expression
      of N-linked glycoprotein backbone structures and glycoprotein terminal structures
      was established in normal cervical glands. A characteristic pattern of luminal
      lectin reactivity was noted in areas of glandular tubal metaplasia. A consistent
      change in the topographic distribution of carbohydrate structures in cervical
      glandular neoplasia was found. In contrast to cytoplasmic expression in normal
      glands, 90% of adenocarcinomas, 92% of cases of high-grade cervical glandular
      intraepithelial neoplasia, and 63% of cases of low-grade cervical glandular
      intraepithelial neoplasia showed novel linear expression along the lumina of
      glands. The results indicate molecular as well as morphological similarities
      between invasive adenocarcinomas and putative preinvasive glandular lesions.

PMID- 7814195
TI  - Expression of the proliferating cell nuclear antigen in cervical neoplasia.
AB  - The expression of the proliferating cell nuclear antigen (PCNA) was examined to
      determine the proliferative activity of the cells in nonneoplastic and neoplastic
      lesions of the uterine ectocervix. Formalin-fixed, paraffin-embedded tissue
      sections of uterine cervix including normal, metaplasia, condyloma,
      intraepithelial neoplasia and invasive squamous cell carcinoma were stained
      immunohistochemically using monoclonal antibody to PCNA. The percentage of PCNA
      positive cells was significantly higher in premalignant and malignant lesions of
      the uterine cervix than in nonneoplastic lesions. Furthermore, the growth
      fraction of tumor cells as detected by PCNA was increased in accordance with the
      progression of neoplasia. The results of this study suggest that the cell
      proliferation index as detected immunohistochemically using PCNA may be a useful
      adjunct to histological diagnosis of various grades of dysplasia.

PMID- 7814194
TI  - DNA content in cervical carcinoma: a flow cytometric assessment of DNA
      heterogeneity.
AB  - The degree of DNA heterogeneity varies between tumors arising in different body
      sites. Any substantial degree of variability within a given tumor can give rise
      to significant problems in the interpretation of DNA flow cytometric (FCM)
      studies. This study was undertaken to evaluate the degree of DNA heterogeneity in
      cervical carcinomas. A total of 100 3-mm punch biopsies were evaluated from
      single large cases in 10 sections of cervical carcinoma. Of the 10 tumors, 6 were
      squamous carcinoma, 1 was an adenocarcinoma, 1 was a mixed small cell and
      squamous carcinoma, 1 was an adenosquamous cancer, and 1 was a small cell
      carcinoma with a small area of adenocarcinoma. Adequate histograms were available
      for 95 (95%) of the samples. Of the 10 cases studied, 9 (90%) revealed
      homogeneity in the DNA pattern. A solitary case demonstrated heterogeneity in one
      histogram (nine samples DNA diploid and one sample DNA aneuploid). This case was
      predominantly small cell undifferentiated carcinoma with focal adenocarcinoma.
      The area of adenocarcinoma was probably the area that contributed to the
      heterogeneous FCM pattern. From this study we conclude that for most cervical
      carcinomas of a specific histologic type there is DNA homogeneity. However, for
      carcinomas with a mixed morphology, DNA heterogeneity is possible and this must
      be taken into account in any DNA ploidy studies that include mixed or combined
      tumors.

PMID- 7814196
TI  - Frequent immunohistochemical detection of EGF supergene family members in ovarian
      carcinogenesis.
AB  - Primary and metastatic ovarian cystadenocarcinomas, carcinomas of low malignant
      potential (borderline tumors), benign ovarian cystadenomas, and normal ovaries
      were compared for immunoperoxidase detection of the ligands epidermal growth
      factor (EGF), transforming growth factor-alpha (TGF-alpha), amphiregulin (AR),
      cripto, and the receptors, epidermal growth factor receptor (EGF-R), and c-erbB
      2. This matrix analysis of these EGF family members indicated no specific pattern
      of ligand or receptor expression with a specific ovarian histologic category
      except in the case of AR and TGF-alpha. AR was detected almost exclusively in
      borderline tumors, suggesting that these tumors may not arise as a pathological
      continuum between benign cystadenomas and invasive cystadenocarcinomas. Second,
      the presence of TGF-alpha immunoreactivity in the absence of coexpression of
      cripto or EGF appeared to be associated only with adenocarcinomas of high grade
      and stage.

PMID- 7814197
TI  - Immunohistochemical analysis of the peritoneum adjacent to endometriotic lesions
      using antibodies for Ber-EP4 antigen, estrogen receptors, and progesterone
      receptors: implication of peritoneal metaplasia in the pathogenesis of
      endometriosis.
AB  - This study was designed to investigate whether or not the pelvic peritoneum
      exhibits a metaplastic process into mullerian-type epithelium using a marker for
      epithelial differentiation (Ber-EP4 antigen) and markers that indicate mullerian
      differentiation (estrogen receptors and progesterone receptors). The peritoneum
      and/or ovarian surface epithelium adjacent to endometriotic lesions were obtained
      from 24 patients with endometriosis at operation, and peritoneum and ovarian
      surface epithelium without any lesions were also obtained from control patients
      without endometriosis. The specimens were immunohistochemically analyzed using
      antibodies for epithelial antigen Ber-EP4, estrogen receptor (ER), and
      progesterone receptor (PR) on frozen sections. Normal peritoneal mesothelium
      showed negative staining for Ber-EP4, ER, and PR. The mesothelium of the
      peritoneum adjacent to the endometriotic lesions showed focal positivity for Ber
      EP4, ER, and PR. Several cases of ovarian surface epithelium from normal control
      ovaries and ovaries adjacent to endometriotic lesions also showed focal
      positivity for Ber-EP4, ER, and PR. Stromal cells accompanying these foci were
      sporadically positive for ER and/or PR but negative for Ber-EP4. Focal expression
      of Ber-EP4, ER, and PR in the mesothelium of the peritoneum and the ovarian
      surface epithelium adjacent to endometriotic lesions suggests that mesothelium
      possibly acquires characteristics of epithelial as well as mullerian-type nature.
      These results support an existence of a metaplastic process of the peritoneal
      mesothelium in the pathogenesis of endometriosis. The more frequent Ber-EP4
      positivity in normal ovarian surface epithelium compared to normal peritoneal
      mesothelium also suggests a fundamental difference in these tissues that may be
      related to the greater prevalence of epithelial neoplasms arising in ovarian
      tissue.

PMID- 7814198
TI  - Glomus tumor of the female external genitalia: a report of two cases.
AB  - Glomus tumors occurring in the external genitalia of two women aged 53 and 46
      years, respectively, are reported. One of the tumors was clitoral and the other
      arose in the periurethral area of the vulva. The diagnosis in one case was
      supported by immunocytochemical analysis. Electron microscopy was performed on
      both tumors. Only two glomus tumors involving the female external genitalia have
      been reported in the literature. The tumors we describe appeared to be
      morphologically similar to the glomus tumors that typically arise in the distal
      extremities.

PMID- 7814199
TI  - Encircling panretinal laser photocoagulation may prevent macular detachment after
      vitrectomy for proliferative diabetic retinopathy.
AB  - Macular detachment due to peripheral retinal tears that occur after pars plana
      vitrectomy for proliferative diabetic retinopathy can result in severe visual
      loss despite successful retinal reattachment. The authors reviewed the records of
      three patients who developed peripheral sclerotomy-related rhegmatogenous retinal
      detachments one to six months after vitrectomy for proliferative diabetic
      retinopathy, despite the absence of detectable sclerotomy-related retinal tears
      by indirect ophthalmoscopy and scleral depression at the conclusion of surgery.
      All three patients had received standard panretinal laser photocoagulation in a
      complete encircling pattern either prior to or during the initial vitrectomy.
      Clinically or echographically, each patient was seen to have a partial or
      complete annual peripheral sclerotomy-related rhegmatogenous retinal detachment
      delimited to the equator. In each of these three cases, posterior extension of
      the peripheral retinal detachment into the macular area was prevented by the most
      anterior row of the photocoagulation scars. Standard panretinal laser
      photocoagulation applied in a complete encircling pattern may be useful in the
      prophylaxis of macular detachment from sclerotomy-related retinal tears that
      occur after vitrectomy for proliferative diabetic retinopathy.

PMID- 7814200
TI  - Predicting surgical compliance in a cohort of women with trichiasis.
AB  - Trichiasis/Entropion are the severe consequences of chronic trachoma during early
      life. Blindness and vision loss is preventable with timely lid surgery to correct
      trichiasis. In a trachoma hyperendemic region of Central Tanzania, a two year
      follow-up survey was conducted among 205 women with trichiasis to determine the
      proportion who had had surgery and the barriers to having surgery. Only 18% of
      the women had undergone surgery by the 2 year follow-up. Those who had surgery
      tended to report more eye problems at baseline and have more corneal opacities at
      baseline. Barriers preventing women from going to surgery were costs, problem of
      children left at home alone, and difficulties in identifying someone to accompany
      them to the health center. Over 2/3 of those who had surgery reported a
      significant decrease in pain, improvement of vision, and improved ability to
      carry out activities of daily life. Ways to improve compliance with
      recommendations for trichiasis surgery need to be developed.

PMID- 7814201
TI  - Pars planitis in a family.
AB  - The familial occurrence of pars planitis is rare. We have found ten cases
      reported previously. We describe a new case of pars planitis in a family. The
      affected members included a mother and two of her four children. The family was
      tested for HLA antigens in order to establish a comparison with others HLA types
      by different authors. We have not identified any cause for the familial
      occurrence of this disease. We discuss the role of genetic and ambiental factors.

PMID- 7814202
TI  - Choroidal tubercles with tuberculous meningitis.
AB  - We found choroidal tubercles in two children with meningitis. This finding
      supposed an important clue in establishing a tuberculous etiology. Following, we
      discuss the evolution and fluorescein angiographic findings of choroidal
      tubercles. As many authors have remarked, a thorough fundus examination is of
      great value in cases of fever of undetermined origin and meningitis. Choroidal
      tubercles can also be the first sign of a common pulmonary or extrapulmonary
      tuberculosis.

PMID- 7814203
TI  - Laser sclerostomy ab interno using continuous wave and pulsed lasers in a rabbit
      model.
AB  - PURPOSE: This experimental study was designed to find an optimal combination of
      parameters for a gonioscopic ab interno approach to laser sclerostomy. METHODS:
      Laser sclerostomy ab interno was performed delivering the laser energy via a slit
      lamp and a gonioscopic contact lens to the iridocorneal angle. The laser energy
      is required to be well transmitted by the cornea and at the same time to be
      maximally absorbed by the sclera at the iridocorneal angle. For local enhancement
      of absorption the sclera was stained with the biocompatible dyes Fluorescein
      (absorption maximum at 480 nm) and Methylene blue (absorption maximum at 668 nm)
      applied by iontophoresis. A continuous-wave (cw)-Argon laser and a cw-dye laser
      produced relatively long pulses (200 ms) at wavelengths matching with these
      respective maxima. Additionally a pulsed dye laser emitting shorter pulses (2
      microseconds) was successively adapted to the wavelengths of the two maxima. In
      some cases a Q-switched Nd: YAG laser had to be used for perforation of
      Descemet's membrane. A total of 44 rabbit eyes was treated to compare the results
      for these four different laser/dye combinations. RESULTS: While no successfull
      perforation of the sclera could be achieved using the cw-dye laser with scleral
      staining by Methylene blue, the intraoperative success rate ranged between 59%
      and 75% for the other three laser/dye combinations. Histological examinations of
      the eyes on the first postoperative day showed smaller thermal necrosis zones,
      but more often fibrin reactions when using the shorter pulse length. Although we
      often found iris adherences to the internal fistula ostium, no major
      complications were observed. CONCLUSION: Further improvement of intraoperative
      success rates is needed, before clinical application of the approach can be
      considered.

PMID- 7814204
TI  - The influence of the incision length on the early postoperative intraocular
      pressure following cataract surgery.
AB  - In a prospective study we recorded the early postoperative intraocular pressure
      of 60 eyes following phacoemulsification and posterior chamber lens implantation.
      In 30 patients each the implantation either of a folded polyHema intraocular lens
      through a 3.5 mm incision or of a polymethylmetacrylate intraocular lens through
      a 7 mm incision was performed. Healon was used in all eyes and thoroughly
      evacuated from the capsular bag behind the implanted lens and the anterior
      chamber. For intraoperative miosis 0.5 ml acetylcholine chloride was injected
      into the anterior chamber after wound closure. Intraocular pressure was measured
      preoperatively as well as six hours, 18 hours, one week and two months
      postoperatively without the influence of antiglaucomatous medication. We found no
      statistically significant change of intraocular pressure at any measurement time
      in the 3.5 mm group (Student's t-test, p > 0.1). In the 7 mm group only the rise
      of intraocular pressure at 18 hours was statistically significant (p < 0.05,
      student's t-test). The comparison of the changes of intraocular pressure from
      preoperative values between both groups revealed a statistically significant
      difference at 18 hours (p < 0.05, student's t-test) but not at any other time
      recorded. Intraocular pressure exceeding 22 mmHg was found at 6 hours in 4
      (13.3%) patients of both groups and at 18 hours in 3 (10%) eyes of the 3.5 mm
      group and 5 (16%) eyes of the 7 mm group (p > 0.1, Fisher's Exact Test). From
      these results we conclude that 1) regardless of the wound size the pressure
      rising effect of Healon is successfully counteracted by the aspiration technique
      described, and 2) with small-incision cataract surgery statistically significant
      less changes of intraocular pressure are observed in the early postoperative
      period.

PMID- 7814205
TI  - The source of embolism in amaurosis fugax and retinal artery occlusion.
AB  - To assess the diagnostic value of an extensive cardiac screening and of carotid
      artery duplex scanning in patients suspected of suffering from retinal embolism,
      we examined 41 consecutive patients (mean age 59.6 years, range 36-74) who
      presented either with amaurosis fugax or with a retinal artery occlusion. In
      spite of extensive investigations, we found no cause in 27 patients (66%). In 11
      patients (27%), symptoms were likely to be due to a stenosis or an occlusion of
      the ipsilateral carotid artery. In only 1 patient (2%), the heart was likely to
      be a source of embolism. We conclude that in patients in this age group suffering
      from either amaurosis fugax or a retinal artery occlusion, a carotid artery
      duplex scanning should be performed first as this investigation is more likely to
      provide useful information than an extensive cardiac screening (ECG, Holter 24
      hour monitoring and precordial echocardiography).

PMID- 7814206
TI  - Antichlamydial activity of lacrimal fluid in patients with trachoma.
AB  - The effect of lacrimal fluid on the growth of Chlamydia trachomatis in
      cycloheximide-treated McCoy cells was studied in 172 persons with active trachoma
      (Group A), in 54 with scarring trachoma (Group B) and in 40 healthy subjects
      (Group C). The patients in groups A and B were treated with tetracycline eye
      ointment for 4-6 weeks after which tears were collected for retesting. Pooled
      lacrimal fluid from patients with active trachoma, collected before treatment,
      had a higher antichlamydial activity compared with healthy individuals. No
      reduction of the chlamydial inclusion count was seen with such fluid from
      patients with scarring trachoma. After tetracycline treatment, patients with
      active trachoma had a slight decrease in their inhibitory activity. In patients
      with scarring trachoma, the treatment did not significantly reduce the inclusion
      count. Antichlamydial antibodies were detected more often in patients with active
      trachoma than in patients with scarring trachoma, while the healthy individuals
      had no such antibodies. Ultrafiltered and nonfiltered lacrimal fluids were
      equally effective in inhibiting C. trachomatis inclusion-formation. The
      inhibitory principle had a molecular weight of less than 10,000 Da.

PMID- 7814207
TI  - Contact diode laser: high power application through fiberoptic cutting tips.
AB  - Diode laser energy has been applied through a fiberoptic probe using a power
      setting of 2.5 watts (W) in the continuous mode. In this study we employed high
      power diode laser energy (4 to 12 W, continuous wave) to incise ocular tissue
      through a fiberoptic probe using 100 microns and 300 microns tips. The retina was
      photocoagulated with a 300 microns orb tip. No bleeding occurred at the incision
      sites. Histologic evaluation revealed coagulation into the healthy tissue ranging
      from 10 to 50 microns.

PMID- 7814208
TI  - The surgical management of retinopathy of prematurity using a perfluorocarbon
      liquid.
AB  - Retinopathy of prematurity with retinal detachment continues to present a
      challenge to the vitreoretinal surgeon despite many advances in technique. We
      report on two eyes with stage 4 and 5 ROP operated on using vitrectomy techniques
      and a perfluorocarbon liquid (Vitreon). The surgical technique is described in
      detail.

PMID- 7814209
TI  - The role of the striatum in motor learning: dissociations between isometric motor
      control processes in Parkinson's disease.
AB  - Studies of Parkinson's disease (PD) have been used to support the hypothesis that
      the striatum serves procedural learning but interpretation of the results is
      confounded by extra-striate pathology and coincidental non-procedural cognitive
      deficits. The motor deficit of PD involves particularly internally cued movement,
      without visual feedback, because of disruption to frontostriatal circuits. Thus,
      we used a non-visual isometric task as a sensitive measure of motor learning in
      early non-demented patients with PD and examined the effects of dopamine
      replacement. The PD group showed disproportionate under-shooting of the target
      but normal motor learning. Learning correlated with some cognitive measures but
      not clinical motor disability or depression. Treatment had no effect on
      performance, despite clinical improvement. The results indicate dissociations
      between motor control processes resulting from striatal pathology. Putaminal
      circuits are involved in force generation and prediction but not critically in
      motor learning.

PMID- 7814210
TI  - Laterality, sexual orientation, and immune system functioning: is there a
      relationship?
AB  - There have been numerous recent investigations of the possibility that laterality
      (the extent to which an individual is right or left-sided or, more usually, right
      or left-handed), sexual orientation (homosexual, bisexual, or heterosexual), and
      immune system functioning are related. The reasons for inconsistencies in the
      literature and failures to reject the null hypothesis are discussed. Additional
      data are presented that show a positive relationship between left-sided
      laterality and homosexuality for a sample of HIV positive males. Immune system
      disorders were not associated with any of the other variables. It is concluded
      that increased left-sidedness is more likely in homosexual men as a group, but
      laterality cannot be used to differentiate homosexual men further into categories
      that vary in their susceptibility to immune disorders.

PMID- 7814211
TI  - Early and midlife exposure to anesthesia and age of onset of Alzheimer's disease.
AB  - Patients with Alzheimer's disease (AD) who have a late onset of dementia may
      represent a subgroup of AD that has a unique multifactorial/genetic profile. It
      was hypothesized in the present study that if external factors interact with a
      biological or genetic susceptibility in at least some subsets of patients with
      AD, these factors may accelerate the manifestation of the disease. The cumulative
      exposure to different types of general and major regional anesthetics prior to
      the onset of dementia was calculated in a population-based study of incident
      cases of AD residing in Rochester, MN, for more than 40 years preceding the onset
      of dementia (N = 252). Correlational analysis revealed that age of onset was
      inversely related to cumulative exposure to general and spinal anesthesia before
      the age of 50, whereas there was no, or an expected positive, correlation for
      anesthetic exposure after 50 years. These findings may suggest that the
      manifestation of dementia in AD patients may be related to exposure to external
      factors at an earlier age.

PMID- 7814212
TI  - Frontal-type memory impairment associated with thalamic damage.
AB  - The present case report adds further evidence to the hypothesis that material
      specific memory problems arise from unilateral thalamic damage and that frontal
      cortical dysfunction may affect the nature of the memory disorder. A 64-year old
      patient who had suffered an ischemic lesion limited to the right anterior
      thalamus showed marked deficits in immediate and delayed recall of visuospatial
      material and face recognition. In addition, there was evidence of frontal-type
      memory problems including impaired spatial working memory, increased forgetting
      rates, poor prospective memory and inadequate elaborative encoding. Concomitant
      behavioral changes characterized by increased irritability and disinhibition also
      supported the hypothesis of frontal lobe dysfunction after thalamic damage.

PMID- 7814213
TI  - Lack of experimental support for Kuznetsov's criticism of biological evolution.

PMID- 7814214
TI  - Further observations on the effects of external picoTesla range magnetic fields
      on visual memory and visuospatial functions in multiple sclerosis.
AB  - The occurrence of cognitive deficits in patients with multiple sclerosis (MS) has
      been recognized since 1877 when Charcot first observed "enfeeblement of memory"
      in his patients and subsequently Gowers (1893) described "failure of memory." The
      presence of cognitive deficits in MS may be a major cause of disability which is
      often severe enough to preclude employment. Impairment of memory including visual
      memory is one of the most common features of the dementia of MS and may be
      evident in early stages of the disease. Disturbances of visuospatial and
      visuomotor functions are also commonly encountered in MS patients reflecting the
      multiplicity of lesion sites in the disease. Recently, I have reported that
      treatment with magnetic fields (MF) in the picoTesla range is an efficacious
      modality in the management of MS and have demonstrated improvement in
      visuospatial functions with this treatment modality. In the present communication
      I present four additional patients with MS in whom application of these extremely
      weak MF produced an improvement in visual memory as well as visuospatial and
      visuomotor functions. The data presented demonstrate the unique efficacy of this
      treatment modality in reversing some of the cognitive deficits associated with
      MS.

PMID- 7814215
TI  - Depressed immune response in malnourished rats correlates with increased thymic
      noradrenaline level.
AB  - Depressed immune response is well documented in protein-calorie malnutrition
      (PCM). Also, central and peripheral noradrenaline (NA) activities have been
      reported to be increased in malnourished animals. Since increases in central and
      peripheral NA may inhibit immune function, it is possible that malnutrition
      induced immunodepression could be mediated by noradrenergic hyperactivity. To
      address this hypothesis the effect of malnutrition on cell-mediated immune
      response, as well as on NA levels of the median eminence, spleen and thymus was
      studied in PCM rats. Decreased lymphoproliferative response and IL-1 production
      by mononuclear macrophages was observed in PCM. Besides, increased NA
      concentration was detected in thymuses of PCM rats, while unchanged levels of
      this neurotransmitter were observed in median eminence and spleen. These data
      suggest a positive correlation between malnutrition-induced immunodepression and
      sympathetic noradrenergic activity in thymus, an organ implicated in immune cell
      differentiation during early development.

PMID- 7814216
TI  - Stimulation of rat pineal melatonin biosynthesis by N-acetylserotonin.
AB  - Rat pineal content of melatonin and related indoles (HPLC-fluorimetric procedure)
      was evaluated after injections of N-acetylserotonin, the immediate precursor of
      melatonin. The increase of melatonin and NAS but of no other indoles was observed
      after daytime (but not after nighttime) NAS administration. NAS-induced
      stimulation of melatonin biosynthesis was dose- and time-dependent. Maximum
      pineal melatonin levels after NAS injections were similar to physiological night
      time peak of melatonin levels. It is suggested that NAS-induced stimulation of
      pineal melatonin biosynthesis might be used as the physiological way of pineal
      gland stimulation for diagnostic and therapeutic purposes.

PMID- 7814217
TI  - Rapid normalization of visual evoked potentials by picoTesla range magnetic
      fields in chronic progressive multiple sclerosis.
AB  - This communication concerns a 55 year old woman with a 5 year history of chronic
      progressive multiple sclerosis (MS) in whom a single external application of
      extremely low magnetic fields (MF) (7.5 picoTesla; 5 Hz frequency) of 20 minutes
      duration resulted in a rapid improvement in symptoms including vision, cerebellar
      symptomatology (ataxia and dysarthria), bladder functions, mood, sleep, cognitive
      functions and fatigue. Improvement in the patient's symptoms was associated with
      normalization of the pretreatment abnormal visual evoked potential (VEP)
      latencies within 24 hours after magnetic treatment. The rapid normalization of
      the VEP latencies suggests that recovery did not occur as a result of
      remyelination but probably was related to enhancement of neurotransmitter
      functions. MF have been shown to alter cellular calcium metabolism which may
      facilitate axonal conduction in demyelinating plaques. Furthermore, as MF affects
      the release of the pineal gland's principal hormone, melatonin, which influences
      the release of monoamines, it is also hypothesized that the effects of picoTesla
      MF in MS are partly mediated by the pineal gland which has recently been
      implicated in the pathogenesis of MS (Sandyk, 1992 a).

PMID- 7814218
TI  - Remarkable recovery of visual function in a patient with Leber's optic neuropathy
      and multiple mutations of mitochondrial DNA.
AB  - Almost complete spontaneous recovery in visual function was observed in a male
      patient with Leber's hereditary optic neuropathy (LHON), in spite of the presence
      of several LHON-associated "major" and "minor" mutations of mitochondrial DNA.
      Our findings confirm that visual loss in LHON may be reversible, and challenge
      the hypothesis of a "synergistic" effect of multiple mtDNA mutations in the
      phenotypic expression of the disease.

PMID- 7814219
TI  - Pyrogenic activity of human native and human recombinant interleukins-1 beta:
      stabilization with albumin enhances the pyrogenic action of recombinant IL-1 beta
      delivered into the rabbit brain.
AB  - The pyrogenic potential of natural and recombinant human IL-1 beta in rabbits was
      found to be very similar when the substances were given intravenously. Under
      these conditions, stabilization of rIL-1 beta with human serum albumin (HSA)
      failed to affect the pyrogenic activity of recombinant IL-1 beta. When the two
      preparations were administered directly into the PO/AH area of the brain,
      recombinant IL-1 beta was less pyrogenic than its natural counterpart. This lower
      pyrogenicity of recombinant IL-1 beta was corrected if the injected material
      contained HSA, which is known to stabilize in vitro the biological activities of
      IL-1 beta against slow degradation. The possibility is now considered that the
      central and peripheral systems for IL-1 inactivation are different. The existence
      of an intrabrain IL-1 pool is suggested and its significance for
      neuroimmunomodulation is stressed.

PMID- 7814220
TI  - Sodium carbonate prevents NK cell conditioning by interfering with the US signal.
AB  - The conditioned enhancement of natural killer (NK) cell activity can be blocked
      by the injection of sodium carbonate solution prior to the association of the
      camphor odor conditioned stimulus (CS) with the polyinosinic:polycytidylic acid
      (poly I:C) unconditioned stimulus (US). We have experimentally dissociated the
      memory which is formed for camphor odor from that developed for the association
      of camphor with the US. The memory for the odor of camphor can be allowed to
      develop one day before the administration of the unconditioned stimulus. Sodium
      carbonate appears to act within the central nervous system to block the
      association of the unconditioned stimulus with the conditioned stimulus. The data
      also suggest that in conditioning of NK cell activity, there are two specific
      sites for memory of the response, one for the conditioned stimulus and the other
      for the association of the unconditioned stimulus with the conditioned stimulus.

PMID- 7814221
TI  - Behavioral and immunological events induced by electrical stimulation of the rat
      midbrain periaqueductal gray region.
AB  - We report here on the immunological and behavioral alterations induced by
      stimulation of the mesencephalic periaqueductal gray matter (PAG), a component of
      the brain aversive system. Male Wistar rats were implanted with stimulating
      electrodes in the caudal dorsolateral part of the PAG. After recovery, animals
      were screened for aversive behavior, characterized by running, jumping,
      vocalization or freezing reaction. Then, rats were subdivided to those which
      could control aversive stimulation (AS) by switch-off response (cAS group) and
      those which could not interrupt AS (uAS group). After sensitization with bovine
      serum albumin (BSA) in complete Freund's adjuvant, rats were stimulated 3
      times/week for 40 days, each session lasting 30 min/rat. Immunological assessment
      included antibody production and hypersensitivity skin reactions to BSA 14 and 21
      days after immunization. A behavioral profile of aversively stimulated animals
      was determined by a poststartle response, open field (OF) activity and two-way
      shuttle-box avoidance task. The results revealed elevated antibody production to
      BSA in cAS and lowered in uAS rats, compared to sham-stimulated and intact
      controls. Arthus and delayed hypersensitivity skin reactions increased in PAG
      stimulated animals on day 14 but not on day 21 after immunization. Poststartle
      response was enhanced both in cAS and uAS rats. Along with immunopotentiation,
      administration of cAS produced hyperactivity in OF test and facilitation of the
      active avoidance learning, whereas uAS caused only moderate suppression of
      rearing in a novel OF environment. Physiological implications and possible
      mechanisms that may account for PAG-mediated immunobehavioral changes are
      outlined.

PMID- 7814222
TI  - A retrospective study of 237 sites treated consecutively with guided tissue
      regeneration.
AB  - A number of controversies have arisen concerning the use of guided tissue
      regeneration in conjunction with implant fixtures. Three of these are the effect
      on the regenerative result of material exposure, the type of grafting material
      used, and whether the fixture is placed in an extraction socket or edentulous
      ridge. This study examines these issues in 237 consecutive sites treated with
      guided tissue regeneration.

PMID- 7814224
TI  - Candidates and requirements for single tooth implant prostheses.
AB  - Successful prosthodontic treatment begins with an accurate diagnosis and thorough
      and comprehensive treatment planning. Osseointegration is an integral part of
      prosthodontic treatment planning. When use of the single tooth implant is
      anticipated, there are several procedure objectives that should be considered:
      elimination of pathosis; attainment of ideal fixture alignment and stability;
      protection of teh adjacent teeth; preservation or augmentation of the alveolar
      ridge; attainment of primary closure; and avoidance of mucosal pressure. Esthetic
      and biologic complications are discussed.

PMID- 7814223
TI  - Use of the supraperiosteal envelope in soft tissue grafting for root coverage.
      II. Clinical results.

PMID- 7814225
TI  - Combined dental implant and guided tissue regeneration therapy in humans.
AB  - This study evaluated wound healing and osseointegration of dental implants placed
      in immediate postextraction sockets in humans. Ten healthy adults had one or more
      teeth extracted and replaced with ITI dental implants, which were centered in the
      residual socket and covered with a polytetrafluoroethylene membrane and a flap to
      attain primary closure. Measurements were made to document the relationship of
      bone to implant at the time of implant placement and at the 6-month reentry. All
      implants were clinically osseointegrated at the 6-month reentry procedure; narrow
      bony defects showed complete bone fill, while wide defects showed partial bone
      fill. There was less bone regeneration in areas of thin cortical bone or
      preexisting dehiscences and in implant sites with early membrane exposure.
      Implants placed in immediate postextraction sockets demonstrated successful
      osseointegration with irregular bone-healing patterns, which were related to
      variations in existing bony anatomy and socket location.

PMID- 7814226
TI  - Treatment with dental implants in patients with severe osteoporosis: a case
      report.
AB  - The case report of a woman with severe osteoporosis who was treated with dental
      implants is presented. Polyarthritis was diagnosed in 1955, and a corticosteroid
      medication treatment was started in 1960. During the years, the patient has
      undergone multiple joint surgeries. Dental implants were inserted in the maxilla
      in 1987 and in the mandible in 1988. Due to a compression of the spine, the
      patient lost 12 cm in body height between 1991 and 1993; a spontaneous femur
      fracture was diagnosed in December 1992. However, the arch bone has been stable;
      the 6- and 5-year follow-up results of the maxillary and mandibular implants,
      respectively, are presented.

PMID- 7814227
TI  - Combination treatment using decalcified freeze-dried bone allograft with guided
      tissue regeneration in human periodontal defects: two case reports.
AB  - The ultimate goal of periodontal therapy should not be limited to the
      establishment and maintenance of periodontal health. The potential regeneration
      of the hard and soft periodontal tissues lost to disease also should be
      considered. Two case reports are presented to demonstrate the potential of guided
      tissue regeneration for this purpose.

PMID- 7814228
TI  - Medium- and long-term effectiveness of a counterrotational electric toothbrush on
      plaque removal, gingival bleeding, and probing pocket depth.
AB  - This study analyzed the difference in effectiveness of a well-known manual
      toothbrush and a counterrotational electric toothbrush over medium- and long-term
      periods. Six dental students and six patients with moderate periodontitis
      participated in a split-mouth, single-blind experiment with repeated recordings
      of pocket depths and plaque and gingivitis indices. During the experiment, the
      use of interdental aids or mouth rinses was forbidden. At all intervals up to
      week 34, manual brushing resulted in significantly less plaque removal,
      especially at approximal sites. Use of the counterrotational electric toothbrush
      resulted in a significantly greater reduction in gingival inflammation and
      significantly increased pocket reduction, especially in the periodontitis group.
      A crossover experiment confirmed the inferiority of the manual cleaning. The long
      term observations showed a slight decrease in efficiency of both brushes, thereby
      justifying the need for regular motivation reinforcement. The results of the
      current study demonstrate the long-term superiority of a counterrotational
      electric toothbrush over the manual toothbrush.

PMID- 7814229
TI  - 9-Cis beta-carotene as a precursor of retinol isomers in chicks.
AB  - The possibility that 9-cis beta-carotene serves as a precursor for retinol in
      general, and particularly for 9-cis retinol, was studied in chicks, in which the
      9-cis beta-carotene is preferentially accumulated. One week old chicks were fed a
      synthetic diet supplemented with 9-cis and all-trans beta-carotene mixtures, in
      which the 9-cis isomer content was 9, 19.1, 31.2, 40.8, 57.7 or 77.0%. It was
      found that an elevation in the dietary 9-cis beta-carotene level led to a
      decrease in the hepatic retinol stores, despite the increased level of total and
      9-cis beta-carotene in the liver. HPLC chromatography revealed the presence of
      all-trans, 13-cis and 9-cis retinol in the livers. A high 9-cis beta-carotene
      diet brought about a significant, but very small, elevation in the part of the
      cis retinol isomers relative to the all-trans isomer. It was concluded that 9-cis
      beta-carotene has a low activity as a precursor of retinol in general. This
      decreased activity is not due to a low availability of the isomer to the
      enzymatic cleavage. It seems also that 9-cis beta-carotene is not an efficient
      precursor of 9-cis retinol.

PMID- 7814231
TI  - Effect of vitamin E injection on cortisol and white blood cell response to
      surgical stress in dairy cows.
AB  - In 20 dairy cows the effect of a single vitamin E injection on cortisol and white
      blood cell response to surgical stress was investigated. Abdominal surgery
      (omentopexy) was carried out in order to correct a left abomasal displacement.
      Ten hours prior to surgery 10 cows were injected intramuscularly with 10 mg DL
      alpha-tocopheryl acetate per kg body weight. Ten cows (controls) received an
      equivalent volume of injectable water. Over a 72 hour period plasma samples were
      collected. In 8 cows (4 cows from each group) alpha-tocopherol in liver tissue
      was determined. Plasma vitamin E concentrations were significantly higher in
      vitamin E injected cows than in controls in all of the samples after the vitamin
      E injections. Similarly, liver alpha-tocopherol concentrations were significantly
      higher in vitamin E injected cows than in controls. The surgical stress led to
      profoundly increased plasma cortisol levels and leucocytosis due to neutrophilia
      within 5 hours after the surgery. Plasma cortisol levels as well as leucocyte
      counts were not affected by route of vitamin E administration used.

PMID- 7814230
TI  - The relation of alcohol consumption to serum carotenoid and retinol levels.
      Effects of withdrawal.
AB  - The effects of alcohol consumption on plasma concentrations of retinol and
      various carotenoids (beta-carotene, alpha-carotene, zeaxanthin-lutein, lycopene
      and beta-cryptoxanthin) were studied in a control population of 118 supposedly
      healthy men consuming low or moderate amounts of alcohol, and 95 alcoholic
      patients without severe liver disease before and after a withdrawal treatment of
      21 days. There was no significant difference between alcoholics and controls
      regarding plasma retinol level. Conversely, plasma concentrations of all the
      carotenoid fractions were significantly lower in the alcoholic group than in the
      low drinker group. After withdrawal, plasma levels of all the carotenoids
      increased whereas retinol concentration diminished. Adjustment of data for
      various potential confounding factors especially including nutritional intake
      suggests an effect of alcohol on plasma carotenoids and a specific effect of
      withdrawal on plasma retinol, both of them being not only related to nutritional
      status.

PMID- 7814232
TI  - Effect of vitamin E on 4-nitroquinoline 1-oxide-induced lung tumorigenesis in
      mice.
AB  - Oxidative stress may play a partial role in chemically induced tumorigenesis in
      mice. Herein, we investigated the preventive effect of vitamin E on 4
      nitroquinoline 1-oxide (4NQO)-induced oxidative damage on pulmonary nuclei and
      lung tumorigenesis in mice. At 4 weeks after 4NQO injection, the levels of
      nuclear thiobarbituric acid substances (TBARS) and DNA single strand breaks (DNA
      SSB) in the lungs of mice treated with 4NQO were significantly higher than those
      in the control mice. The 4NQO-induced oxidative stress on the nuclei and DNA-SSB
      were significantly inhibited by vitamin E treatment. The nuclear alpha-tocopherol
      level in the 4NQO-treated group was significantly lower than that in the control,
      but the plasma alpha-tocopherol level in the former was slightly lower than that
      in the latter. Vitamin E feeding compensated the decrease of the level in the
      nuclei and plasma. The feeding on excessive vitamin E for 23 weeks after 4NQO
      injection could partly reduce the lung tumor incidence as well as lung tumor
      multiplicity in mice. These findings suggest that vitamin E could partly suppress
      4NQO-induced lung tumorigenesis in mice, probably through the inhibition of 4NQO
      induced oxidative damage on the nuclei.

PMID- 7814233
TI  - Assessment of vitamin E nutritional status in neonates, infants and children--on
      the basis of alpha-tocopherol levels in blood components and buccal mucosal
      cells.
AB  - We examined the age-related changes of alpha-tocopherol levels in various
      clinically available biosamples in order to assess the vitamin E nutritional
      status. During the first week of life, more than half of every sample except red
      blood cells showed alpha-tocopherol levels below the lower limit of normal in a
      control group of children aged 3-16 years. alpha-Tocopherol levels in mononuclear
      leucocytes and buccal mucosal cells, which possess LDL receptors, increased in
      response to the plasma alpha-tocopherol elevation within a week after birth.
      However, RBC and platelet levels did not respond so quickly. Considering the
      transfer of tocopherol into body tissues during LDL catabolism, the determination
      of tocopherol levels in cells with LDL receptors may be useful for assessing the
      vitamin E status and our present study suggests that the tissue vitamin E status
      may be marginal in neonates.

PMID- 7814234
TI  - Potential role of ascorbic acid and beta-carotene in the prevention of preterm
      rupture of fetal membranes.
AB  - The association of antioxidant vitamins in serum and amniotic fluid with preterm
      rupture of fetal membrane (PROM) was examined. Amniotic fluid and venous blood
      specimens from 80 pregnant women with or without PROM were analyzed for ascorbic
      acid (ASA), alpha-tocopherol, retinol and beta-carotene concentrations. No
      differences in retinol and alpha-tocopherol in amniotic fluid or serum
      concentrations were found between the PROM and control groups. PROM and control
      subjects had similar serum ASA concentrations. However, PROM subjects had lower
      amniotic fluid ASA concentrations (p < 0.0001) and lower ratios of amniotic fluid
      ASA to serum ASA concentration than those of controls. Serum beta-carotene levels
      were lower in PROM group than control group (p = 0.025). The findings suggest
      that a low level of ASA in amniotic fluid but not serum appears to be an
      important determinant of PROM. beta-Carotene and ASA may act synergistically to
      prevent PROM in smokers.

PMID- 7814235
TI  - Interrelationships between riboflavin and vitamin B6 among elderly people (Dutch
      Nutrition Surveillance System).
AB  - Vitamin B6 is considered to be a risk nutrient for elderly people. Conversion of
      most naturally available vitamin B6 to its functional coenzyme pyridoxal 5'
      phosphate (PLP) depends on riboflavin. Therefore, interrelations were studied
      between riboflavin and vitamin B6 among 473 elderly people not using supplements
      containing B-vitamins. Habitual food consumption (assessed through dietary
      history with cross-check), plasma PLP levels and enzyme activities of erythrocyte
      glutathione reductase (EGR) and erythrocyte aspartate aminotransferase (EAST),
      with and without added flavin adenine dinucleotide and PLP, respectively, were
      determined. The results showed that unstimulated and stimulated EAST activity was
      higher when EGR activity (both simulated and unstimulated) was higher. Plasma PLP
      was positively associated with (un)stimulated EGR activities, but these
      correlations were not significant, probably due to the lower number of
      observations. Adjusted for the intake of vitamin B6 similar observations were
      made for the forementioned interactions between the biochemical indicators. To
      identify the strongest correlates of the vitamin B6 status indicators, stepwise
      regression analysis was carried out. The results showed that in each model an
      indicator of the riboflavin status was included. Our findings suggest an
      interaction between the status of riboflavin and vitamin B6 at intake levels
      normally found among Dutch elderly people.

PMID- 7814236
TI  - Zinc, copper and iron balance in the vitamin B-6-deficient rat.
AB  - Zinc (Zn), copper (Cu) and iron (Fe) balance was assessed over 8 weeks in 3
      groups of young male Wistar rats receiving a daily pyridoxine hydrochloride (PN
      HCl) intake of 45, 23 and 0 micrograms respectively. Although all 3 groups
      remained in a positive balance throughout the study the Zn and Cu balance, growth
      and food intake was significantly lower in the group receiving no PN-HCl (p <
      0.05). The lowered Zn and Cu balance in this group resulted from a decreased food
      intake coupled with an increased excretion of Zn and Cu. The group receiving 23
      micrograms/d of PN-HCl showed no significant difference in growth, food intake
      and Zn and Cu balance when compared to the group receiving 45 micrograms/d,
      indicating that subminimal levels of vitamin may still be exerting beneficial
      effects on the balance of these trace elements.

PMID- 7814237
TI  - The clinical effects of vitamin C supplementation in elderly hospitalised
      patients with acute respiratory infections.
AB  - A randomised double-blind trial involving vitamin C/placebo supplementation was
      conducted on 57 elderly patients admitted to hospital with acute respiratory
      infections (bronchitis and bronchopneumonia). Patients were assessed clinically
      and biochemically on admission and again at 2 and 4 weeks after admission having
      received either 200 mg vitamin C per day, or placebo. This relatively modest oral
      dose led to a significant increase in plasma and white cell vitamin C
      concentration even in the presence of acute respiratory infection. Using a
      clinical scoring system based on major symptoms of the respiratory condition,
      patients supplemented with the vitamin fared significantly better than those on
      placebo. This was particularly the case for those commencing the trial most
      severely ill, many of whom had very low plasma and white cell vitamin C
      concentrations on admission. Various mechanisms by which vitamin C could assist
      this type of patient are discussed.

PMID- 7814238
TI  - Vitamin status of a healthy French population: dietary intakes and biochemical
      markers.
AB  - The vitamin status of a representative population sample in a French district in
      the Paris area was assessed using a biochemical and dietary approach. Complete
      data were obtained for 1039 subjects 6 to 97 years old. Dietary intakes of most
      vitamins increased up to adolescence and then remained stable or decreased
      slightly in adult life. Total vitamin intakes were higher in men than in women
      (except for ascorbic acid), but the vitamin density of the diet was higher in
      females. Most subjects presented dietary intakes below the French recommended
      allowances for vitamin B1, B6, C, A and E. A variation in biochemical parameters
      according to age and sex was observed only for serum concentration of retinol,
      beta-carotene, vitamin E and C. Multiple regression analysis showed that dietary
      vitamin intakes were related to the biological status for vitamin B2, B6, C,
      folates, beta-carotene and vitamin E. Tobacco smoking, alcohol consumption and
      oral contraceptive were significantly correlated with biological status for
      several vitamins. While biochemical evidence of severe vitamin deficiency was not
      observed, a sizeable minority of the French population is not lavishly supplied
      with some vitamins, and this situation deserves investigation to see if any
      deleterious effects are associated with it.

PMID- 7814239
TI  - Manganese content of European wines.
AB  - The manganese content of 35 different red, white and rose wines, produced in
      several European countries, is determined by electrothermal atomic absorption
      spectrometry. A mean concentration of 2.7 +/- 1.7 mg l-1 (range: 0.5-7.3 mg l-1)
      is obtained. No statistically significant difference is observed between red and
      white wines. On the other side, the red Beaujolais wines reveal significantly (p
      < 0.01) higher manganese content. Since literature data on manganese content of
      wine could hardly be traced, factors, probably affecting the manganese content of
      this alcoholic beverage, are discussed.

PMID- 7814240
TI  - The effect of consumption of fish oil-enriched spreadable fats on platelet
      phospholipid fatty acid composition in human volunteers.
AB  - Thirty-three male subjects were randomly allocated to one of three treatments
      which involved the consumption of 50 g/d of either one of three spreadable fats
      for twelve weeks. Group A consumed their normal spreadable fat; group B consumed
      a low-fat spread (40% fat wt/wt) which contained 8 g of fish oil per 100 g of
      product; group C consumed a high-fat spread (80% fat wt/wt) which contained 8 g
      of fish oil per 100 of product. Baseline levels of platelet phospholipid
      eicosapentaenoic acid (C20:5 n-3) were < 1.0% wt/wt at baseline in all groups and
      increased significantly (p < 0.05) in both groups receiving fish-oil containing
      spreads (12 week values of 1.5 +/- 0.5 for group B and 2.4 +/- 1.3 for group C).
      There was no change in the control group receiving their normal spreads. The
      ratio of all n-6; n-3 polyunsaturated fatty acids fell significantly in group B
      (12.5 +/- 3.1 v 1.7 +/- 1.9) and in group C (8.2 +/- 3.9 v 6.7 +/- 2.6), both of
      whom received fish oil. These two groups also achieved a significant (p < 0.05)
      increase in platelet phospholipid docosahexaenoic acid (C22: 6 n-3): 2.3 +/- 0.5
      v 2.9 +/- 0.9 in group B and 2.3 +/- 0.6 v 3.1 +/- 0.9 in group C. The subjects
      encountered no important palatability or acceptability difficulties. These data
      show that, in individuals with low intakes of fatty fish, spreadable fats
      enriched with fish oil are a useful vehicle for ensuring adequate intakes of n-3
      polyunsaturated fatty acids.

PMID- 7814241
TI  - Immunological aspects of HCV infection.
AB  - The hepatitis C virus (HCV) commonly causes persistent infection and chronic
      liver disease, and it is an important risk factor for the development of
      hepatocellular carcinoma (HCC). The mechanisms responsible for HCV persistence
      and disease pathogenesis are not well understood, although it is likely that both
      direct (virus-induced) and indirect (immunologically mediated) mechanisms play an
      important role. This review focuses on current knowledge of the interactions
      between HCV and the host immune system, emphasizing aspects of the cellular
      immune response. Observations in humans infected with HCV as well as experimental
      HCV infection of chimpanzees suggest that natural HCV infection does not induce
      protective immunity at the humoral or cellular levels. Indeed, anti-HCV
      seroconversion does not prevent reinfection by homologous or independent viral
      inocula. A CD4+ T lymphocyte response directed against all of the putative viral
      proteins occurs in chronically infected patients despite their failure to clear
      the virus. While the HCV core and NS4 proteins seem to be most immunogenic at the
      CD4+ peripheral blood T cell level during chronic HCV infection, there is some
      evidence that the NS4-specific response is preferentially compartmentalized in
      the liver. Similarly, the CD8+ cytotoxic T lymphocyte (CTL) response is
      remarkably polyclonal and multispecific during chronic HCV infection, since
      epitopes located in all of the putative proteins are recognized by the CTL
      present in the peripheral blood and/or the intrahepatic lymphocyte populations
      during this disease.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7814242
TI  - Hepatitis virus-related hepatocarcinogenesis.
AB  - We propose that hepatitis virus can cause an increase in the incidence of liver
      cancer by a combination of two mechanisms: (1) cell killing and stimulation of
      mitosis leading to an accumulation of events necessary for transformation, and
      (2) an increase in chromosomal instability mediated by induced recombinogenic
      protein(s) during chronic hepatitis.

PMID- 7814243
TI  - Epidemiological studies on hepatitis C virus infection: detection, prevalence,
      exposure and prevention.
AB  - Highly sensitive and specific tests for HCV infection are now available for
      epidemiological studies. These include: (1) the second-generation ELISA or
      agglutination technique with supplemental testing; (2) serotyping of antibody;
      (3) detection of HCV-RNA by RT-nested double PCR with the 5' noncoding region for
      the highest sensitivity; (4) quantitation of HCV-RNA; (5) genotyping using
      specific primers in the core region, and (6) sequence analysis of E2/NS1
      hypervariable region 1 to identify homology among HCV isolates. Transmission of
      HCV is commonly done by percutaneous routes, although the route in a significant
      proportion of sporadic infections is unknown. Sexual transmission and perinatal
      transmission appear to be relatively infrequent.

PMID- 7814244
TI  - Genetic heterogeneity of hepatitis C virus.
AB  - There are four hierarchical strata in the genetic heterogeneity of hepatitis C
      virus (HCV): group above subgroup above isolates above quasispecies. The entire
      genome sequence has so far been reported for 16 isolates which are classifiable
      into 3 groups and 6 subgroups. Provisional classification of HCV is also possible
      using a partial sequence of the HCV genome. With the E1 region sequence for
      example, the present collection of HCV isolates can be classified into 9 groups
      and 23 subgroups. The rationale for these classifications and the epidemiological
      and clinical implications of genotyping HCV are reviewed.

PMID- 7814245
TI  - Non-anticoagulation in atrial fibrillation.
AB  - Atrial fibrillation (AF) is an important risk factor for stroke and
      anticoagulation is now indicated in many patients at increased risk. Studies
      however have shown that many patients at risk are not anticoagulated for reasons
      that are not well explored. We identified prospectively the reasons for non
      anticoagulation in patients with AF in 94 consecutive hospital patients with
      cardiac or cerebrovascular disease who had AF. Patients with intermittent or lone
      AF and < 60 years were excluded n = 16. The remaining group had a mean age of 76
      +/- 7 years with a mental test score of 7.4 +/- 2 (normal 10), 31 lived alone and
      they lived an average of 14 +/- 11 miles from the hospital laboratory. The
      reasons for non-anticoagulation overlapped and were: medical in 29: cognitive
      impairment/compliance in 32: and monitoring problems in 50. Anticoagulation for
      AF in the elderly is a complex enterprise which must take into account social and
      cognitive as well as medical issues.

PMID- 7814247
TI  - Limb salvage in vascular trauma of the extremities--a regional experience.

PMID- 7814246
TI  - Limitations of thyroid scanning in solitary thyroid nodules.
AB  - During an 8-year period, 104 patients (19 males, 85 females) underwent surgery
      for a solitary thyroid nodule. There were 19 (18.3%) malignant nodules and 85
      (81.7%) benign nodules. Malignancy occurred in 3 (15.8%) males and 16 (18.8%)
      females. Pre-operative scanning was performed prior to referral in 59 patients
      (52 had ultrasound, 41 had isotope scanning; the majority had both). Of the
      scanned patients, 12 (20%) had a malignant nodule while 7 (15.5%) of the 45
      patients who did not have scanning had a malignant nodule. In patients who had an
      ultrasound scan, malignancy was found in 5 (23.8%) of the 21 solid nodules and 7
      (22.7%) of the 31 cystic (or solid/cystic) nodules. In patients who had thyroid
      isotope scanning, malignancy was found in 6 (17.5%) of the 34 cold (non
      functioning) nodules and 3 (43%) of the 7 warm or hot (functioning) nodules.
      Ultrasound and isotope scanning may be misleading and neither help to
      differentiate benign from malignant thyroid nodules which require surgical
      excision.

PMID- 7814248
TI  - An irreducible posterolateral knee subluxation.

PMID- 7814249
TI  - Present knowledge about specific absorption rates inside a human body exposed to
      radiofrequency electromagnetic fields.
AB  - We have compiled results of scientific investigations about the relationship
      between external field-strengths and specific absorption rates inside the human
      body. The data were normalized to SAR-values that form the basis for current
      safety standards. Results were compared to exposure limits given in these
      standards. This comparison should serve as a reference for the selection of
      reliable reference levels for personal protection against thermal effects in
      radiofrequency electromagnetic fields. The need to measure and monitor
      ankle/wrist currents to protect some exposed workers is explained. The study has
      also highlighted a scarcity of dosimetric data at frequencies below 3 MHz.

PMID- 7814250
TI  - Test of the linear-no threshold theory of radiation carcinogenesis for inhaled
      radon decay products.
AB  - Data on lung cancer mortality rates vs. average radon concentration in homes for
      1,601 U.S. counties are used to test the linear-no threshold theory. The widely
      recognized problems with ecological studies, as applied to this work, are
      addressed extensively. With or without corrections for variations in smoking
      prevalence, there is a strong tendency for lung cancer rates to decrease with
      increasing radon exposure, in sharp contrast to the increase expected from the
      theory. The discrepancy in slope is about 20 standard deviations. It is shown
      that uncertainties in lung cancer rates, radon exposures, and smoking prevalence
      are not important and that confounding by 54 socioeconomic factors, by geography,
      and by altitude and climate can explain only a small fraction of the discrepancy.
      Effects of known radon-smoking prevalence correlations--rural people have higher
      radon levels and smoke less than urban people, and smokers are exposed to less
      radon than non-smokers--are calculated and found to be trivial. In spite of
      extensive efforts, no potential explanation for the discrepancy other than
      failure of the linear-no threshold theory for carcinogenesis from inhaled radon
      decay products could be found.

PMID- 7814251
TI  - UV-B radiometry and dosimetry for solar measurements.
AB  - Biologically effective irradiance or dose of solar UV radiation was determined
      using a spectroradiometer, two broadband radiometers and two types of passive UV
      dosimeters. The absolute erythema irradiance and the actinic irradiance were
      calculated from the solar spectrum measured with the spectroradiometer. It was
      demonstrated that the erythema irradiance is proportional to the actinic
      irradiance of solar radiation. The erythema irradiance was also determined using
      the two broadband radiometers which utilize a filter transmitting erythema
      spectra. Personal UV-dosimeters such as polysulphone and CR-39 were used to
      determine the erythema dose for a selected period of time. These results were
      used to estimate the accuracy of the broadband radiometers and UV-dosimeters. It
      was found that the results obtained from the broadband radiometers deviate from
      the absolute erythema irradiance by less than 20% during clear days between the
      hours of 11:00 and 13:00 Eastern Standard Time (EST) in Australia. The assessment
      of the erythema dose using passive dosimeters such as polysulphone and CR-39
      could introduce an error as high as 40% if the calibration was not performed
      before undertaking experimental measurements.

PMID- 7814252
TI  - Measurement of radioactivity in Arizona groundwater using improved analytical
      techniques for samples with high dissolved solids.
AB  - Radiochemical analyses of 667 samples collected over the 5-y period 1989 to 1993
      indicate that approximately 2% of Arizona drinking water supplies from
      groundwater sources violate current regulatory standards. About 1% of the
      population is affected. The 1996 change in regulatory requirements will bring
      some Arizona water systems into compliance through 226Ra limit relaxation, while
      others will become noncompliant due to new limits on uranium levels. Maximum
      concentrations in Arizona of adjusted gross alpha, gross beta, and 226Ra
      activities are higher than levels found in the U.S. Environmental Protection
      Agency's national survey. Sampling results show a correlation between
      radionuclide concentration and localized geology. Improved radiochemical methods
      are described that result in greater accuracy and sensitivity for samples high in
      dissolved solids, as are typical in Arizona.

PMID- 7814253
TI  - A comparison of sensitivity analysis techniques.
AB  - Modeling the movement and consequence of radioactive pollutants is critical for
      environmental protection and control of nuclear facilities. Sensitivity analysis
      is an integral part of model development and involves analytical examination of
      input parameters to aid in model validation and provide guidance for future
      research. Sensitivities of 21 input parameters have been analyzed for a specific
      activity tritium dose model using fourteen methods of parameter sensitivity
      analysis. This report demonstrates, for each sensitivity method, the required
      calculational effort, the sensitivity ranking of parameters, and the relative
      method performance. The sensitivity measures include the following: partial
      derivatives, variation of inputs by 1 standard deviation (SD) and by 20%, a
      sensitivity index, an importance index, a relative deviation of the output
      distribution, a relative deviation ratio, partial rank correlation coefficients,
      standardized regression coefficients, rank regression coefficients, the Smirnov
      test, the Cramer-von Mises test, the Mann-Whitney test, and the squared-ranks
      test.

PMID- 7814254
TI  - Gas bremsstrahlung and associated photon-neutron shielding calculations for
      electron storage rings.
AB  - The EGS4 electron-photon Monte Carlo code has been used to study the
      characteristics of the bremsstrahlung x rays generated from the interaction of
      circulating electrons with the residual gas in accelerator storage rings. Gas
      bremsstrahlung dose rates are given for various opening angles as a function of
      the electron beam energy ranging from 0.5-10 GeV. Photon and neutron dose rates,
      generated from various devices struck by gas bremsstrahlung in a synchrotron
      radiation beamline, are also presented along with the photon spectral and
      transmission results. The EGS4-predicted results are found to be in basic
      agreement with the measurements made at the Stanford Synchrotron Radiation
      Laboratory. Figures, equations, and a simple method useful for the photon-neutron
      shielding design for beamlines are provided.

PMID- 7814255
TI  - A study of the angular dependence problem in effective dose equivalent
      assessment.
AB  - The newly revised American National Standard N13.11 (1993) includes measurements
      of angular response as part of personnel dosimeter performance testing. However,
      data on effective dose equivalent (HE), the principle limiting quantity defined
      in International Commission on Radiological Protection (ICRP) Publication 26 and
      later adopted by U.S. Nuclear Regulatory Commission (NRC), for radiation incident
      on the body from off-normal angles are little seen in the literature. The absence
      of scientific data has led to unnecessarily conservative approaches in radiation
      protection practices. This paper presents a new set of fluence-to-HE conversion
      factors as a function of radiation angles and sex for monoenergetic photon beams
      of 0.08, 0.3, and 1.0 MeV. A Monte Carlo transport code (MCNP) and sex-specific
      anthropomorphic phantoms were used in this study. Results indicate that Anterior
      posterior (AP) exposure produces the highest HE per unit photon fluence in all
      cases. Posterior-anterior (PA) exposure produces the highest HE among beams
      incident from the rear half-plane of the body. HE decreases dramatically as one
      departs from the AP and PA orientations. The results also indicate that
      overestimations caused by using isotropic dosimeters in assessing effective dose
      equivalent from near-overhead and near-underfoot exposures are 550%, 390%, and
      254% for 0.08, 0.3, and 1.0 MeV, respectively. Comparisons of the angular
      dependence of HE with those based on the secondary quantities defined in
      International Commission on Radiation Units and Measurements (ICRU) Reports 39,
      43, and 47 show significant differences. This paper discusses why more accurate
      assessments of HE are necessary and possible. An empirical equation is proposed
      which can be used as the optimum dosimeter angular response function for
      radiation angles ranging from 0 degrees to 90 degrees for dosimeter calibration,
      performance testing, and design.

PMID- 7814256
TI  - Soft tissue tumors in beagles injected with 241Am citrate.
AB  - The occurrence of soft tissue tumors has been studied in 117 beagles assigned to
      8 dosage groups of between 2 and 26 animals each and injected with 0.07 to 104
      kBq 241Am kg-1 as the citrate. In addition, 133 control beagles given no
      radioactivity were used as a comparison group. All 250 dogs were maintained under
      identical conditions and were observed for their entire lifespans. An important
      competing risk for the appearance of soft tissue tumors appeared to be the
      occurrence of skeletal malignancy, and at the highest injected activity (104 kBq
      kg-1), kidney and liver failure brought about the death of both of the two dogs
      in this group. Thyroid and liver were the only soft tissues that exhibited
      greater concentrations of 241Am than the skeleton. Liver tumors were associated
      with 241Am exposure (p < 0.001), but the thyroid tumor rate was not increased
      significantly in the irradiated animals (p > 0.10) as compared with the
      occurrence in controls. There was a greater relative occurrence of all vaginal
      tumors in control animals than in dogs given 241Am, a situation also found for
      all tumors of the pancreas, skin, testis, and mammary glands and for malignant
      ovarian tumors. All of these differences were statistically significant. The
      survival of animals given 0.07 to 0.59 kBq 241Am kg-1 could not be established (p
      > 0.10) as significantly different from controls, but the survival of all groups
      given 1.8 to 104 kBq kg-1 was decreased (p < 0.05). There was no indication in
      our studies of a positive association between relative exposure to 241Am and the
      occurrence of mammary tumors, mast cell sarcomas originating outside the liver,
      lymphosarcoma or tumors of marrow, including leukemia.

PMID- 7814257
TI  - Regression models for the determination of the absorbed dose rate with an
      extrapolation chamber for flat ophthalmic applicators.
AB  - The average surface absorbed dose rate, given by flat ophthalmic applicators
      (90Sr/90Y, 925 MBq) is determined in equivalent soft tissue using an
      extrapolation chamber with two flat parallel electrodes of variable separation;
      the input electrode is fixed in relation to the collector electrode of constant
      area. When estimating the extrapolation curve slope using a linear regression
      model, it has been observed that average surface dose rate values were
      underestimated by up to 19%, as compared to estimations of these values by means
      of a second degree polynomial regression model, while an improvement of up to 37%
      is observed in the standard error of the slope in the quadratic model, as
      compared to that of the linear model. With the aim of validating the results of
      these models, goodness of fit tests to a Normal (the Shapiro-Wilk test) as well
      as homogeneity tests on treatment variance (the Bartlett test) were applied. The
      analysis of variance (ANOVA) tables of fit and residual error breakdown are
      given: table 3a and 3b for linear fit; 7a and 7b for quadratic fit, and table 10
      to error breakdown. Also presented is the global uncertainty of the average dose
      rate, taking into account the reproducibility of the experimental set-up. It may
      be inferred that by using this type of measurement for the extrapolation curve
      slope, quadratic regression models allow for a greater degree of accuracy and
      precision in determining surface dose rate values. The effective area of the
      collector electrode and the effective electrode separation in the chamber are
      also determined by measuring the chamber's electric capacity. Finally, there is
      an attempt to relate the use of the regression models to the experimental
      conditions during the measurement of ionization currents (diameter of collector
      electrode, electrical field gradient, radiation field uniformity, radiation field
      intensity, etc.). In this particular case, deviations in the distance inverse
      square law and the "screening" effects during the collection of negative charges
      (both for primary radiation and the ionization generated by it), are presented as
      necessary, but insufficient, conditions to explain thoroughly the quadratic
      behavior of ionizing currents.

PMID- 7814258
TI  - Absorbed dose measurements and calculations in phantoms for 1.5 to 50 keV
      photons.
AB  - A Monte Carlo code EGS4 expanded for low energy photon transport was validated by
      measuring absorbed doses in a phantom for 30 and 10 keV monoenergetic photons
      from synchrotron radiation. Using the EGS4 code, depth doses at 0.07 mm, 0.02 to
      0.1 mm, and 10 mm in the ICRU slab phantoms were calculated for 1.5 to 50 keV
      photons using the updated photon cross section data PHOTX. The results show that
      the doses at 0.02 to 0.1 mm below 10 keV are practical indices of effective dose
      as calculated by others, based on the 1990 ICRP recommendations (1991).

PMID- 7814259
TI  - Integrated measurements of 212Pb and 212Bi in the air by rotating filters.
AB  - A method for determining time integrated concentrations of 212Pb and 212Bi in the
      air is proposed. It employs solid state nuclear track detectors covered with an
      absorber and placed around a rotating filter. Results from experiments carried
      out in an artificial 220Rn atmosphere have been presented. They reveal that the
      method works within the range of integrated concentrations for indoor
      measurements. The experimental error was about 7% for 212Pb and 23% for 212Bi.
      Possibilities for improving the accuracy have been discussed.

PMID- 7814260
TI  - Biological dosimetry after extensive diagnostic x-ray exposure.
AB  - The yield of chromosome aberrations (dicentric and ring chromosomes) was
      determined for five patients who had been extensively exposed to diagnostic x
      rays. Remarkably high aberration yields were obtained for each of them leading to
      correspondingly high equivalent whole body doses ("biological dosimetry"). The
      contribution of iodized contrast media and computing tomography to the
      biologically estimated doses is discussed.

PMID- 7814261
TI  - Y-linked suppressors of the sex-ratio trait in Drosophila mediopunctata.
AB  - X-linked meiotic drive causing female-biased progenies is known to occur in nine
      Drosophila species and is called 'sex-ratio'. In D. mediopunctata this trait is
      associated with the X:21 chromosome inversion and has variable expression. We
      describe here a powerful Y-linked suppressor system of sex-ratio expression in
      this species. There are two types of Y chromosomes (suppressor and nonsuppressor)
      and two types of X:21 chromosomes (suppressible and unsuppressible). Sex-ratio
      expression is suppressed in males with the 21suppressible/Ysuppressor genotype,
      whereas the remaining three genotypes produce female-biased progenies.

PMID- 7814262
TI  - The relationship between DNA structural variation and activities of P elements in
      P and Q strains of Drosophila melanogaster.
AB  - To characterize the relationship between P element activities and their
      structures, we cloned P elements from genomic libraries of three isogenic P and Q
      strains derived from natural populations in Japan. These P elements were mapped
      with BamHI, AvaII and PstI and were classified by their size. The majority of P
      elements cloned were classified as either complete or relatively small P elements
      rather than medium size. The numbers of full length (2.9 kb) P elements per
      haploid genome of NP280 (P), AK194 (weak P) and WY113 (Q) were at least four,
      five and one, respectively. However, the 2.9 kb P element of WY113 was thought to
      be defective since this strain has no transposase activity. In our previous work,
      we demonstrated that the ORF 3-deleted P element is essential for P cytotype
      determination in WY113. A similar P element also exists in NP280, and this may
      have an important role for P cytotype determination in this strain. Two and one
      copies of the KP element, a deletion derivative of the P element, were found in
      NP280 and AK194, respectively. One of four complete P elements in NP280 was fully
      sequenced, and the base sequence was completely identical to that of p pi 25.1
      originally derived from the U.S.A. This result is consistent with the notion that
      these P elements have a relatively recent origin in Drosophila melanogaster.

PMID- 7814263
TI  - DNA fingerprinting used to test for family effects on precocious sexual
      maturation in two populations of Oncorhynchus tshawytscha (Chinook salmon).
AB  - Two single locus Variable Number Tandem Repeat (VNTR) DNA probes were used to
      test for differences in allele distribution between precociously mature male and
      immature chinook salmon, Oncorhynchus tshawytscha. Two populations were examined:
      Robertson Creek (RC) adult salmon, and Nicola River (NR) freshwater juveniles, or
      parr. Genomic DNA was extracted from 74 RC precociously mature adult males
      ('jacks') and 94 RC immature adults of the same age and from 45 NR precociously
      mature parr and 51 NR nonmaturing parr. The genomic DNA was hybridized with a
      single locus VNTR probe developed for chinook salmon (OtSL1), as well as one
      developed for Atlantic salmon, Salmo salar (Ssa1). The allele frequency
      distributions at both loci were significantly different for the RC jacks and
      immature fish, indicating a family effect on the incidence of precocious
      maturation in that population. No difference was found between the allele
      frequency distribution of the NR precocious and immature parr. A bin width
      sensitivity analysis showed that the comparisons of the allele frequency
      distributions were insensitive to the choice of bin size. No differences in
      heterozygosity were found between mature and immature fish at either locus for
      both stocks. Preliminary testing for family effects on phenotypes of interest,
      such as alternative life history strategies, can be performed using hypervariable
      VNTR DNA probes, prior to implementing costly and involved breeding programmes.

PMID- 7814264
TI  - Developments in the prediction of effective population size.
AB  - Effective population size is a key parameter in evolutionary and quantitative
      genetics because it measures the rate of genetic drift and inbreeding. Predictive
      equations of effective size under a range of circumstances and some of their
      implications are reviewed in this paper. Derivations are made for the simplest
      cases, and inter-relations between different formulae and methods are discussed.

PMID- 7814265
TI  - Evidence for a genetically encoded map of functional development in the
      cerebellum.

PMID- 7814267
TI  - Extracellular matrix proteins, integrin receptors (VLA-beta 1, VLA-alpha 2 and
      VLA-alpha 5) and growth fraction in atypical macroregenerative nodules of the
      liver: an immunocytochemical case study.
AB  - A case of cirrhotic liver harbouring three atypical macroregenerative nodules and
      an hepatocellular carcinoma was immunocytochemically investigated for the
      expression of VLA-beta 1, VLA-alpha 2 and VLA-alpha 5 integrins and for different
      extracellular matrix (ECM) components (collagen I, collagen IV, laminin,
      fibronectin and tenascin). In addition, the proliferative activity within the
      nodules was evaluated, using the MIB 1 monoclonal antibody (MAb). The cirrhotic
      liver disclosed a continuous staining pattern of the ECM proteins investigated,
      as well as a "sinusoidal" immunostaining of VLA-beta 1, VLA-alpha 2 and VLA-alpha
      5. The macroregenerative nodules showed a discontinued immunoreactivity for ECM
      proteins while maintaining a VLA-beta 1 sinusoidal immunostaining, coupled with
      intercellular immunostaining. VLA-alpha 2 and VLA-alpha 5 expression was lacking.
      The growth fraction was low in both the above pathological conditions. The
      hepatocellular carcinoma was devoid of any ECM immunostaining. VLA-beta 1
      immunoreactivity exhibited a honeycomb pattern of staining, whereas VLA alpha
      subunits were absent. MIB1 expression was high, being present in 30% of
      neoplastic nuclei. A possible relationship between atypical macroregenerative
      nodules and hepatocellular carcinoma is discussed.

PMID- 7814266
TI  - Robert Feulgen Lecture 1994. Cytochemistry and reactive oxygen species: a
      retrospective.
AB  - This retrospective reviews the methodology we have developed over several decades
      for detecting reactive oxygen species (ROS), using the activated
      polymorphonuclear leukocyte (PMN) as the paradigm of a cell which vigorously
      generates ROS through activation of NADPH oxidase. In the seventies, the sites of
      ROS generation by PMN were not clear from biochemical data, and we sought to
      develop new methods for the cytochemical localization of O2.-, H2O2, and the H2O2
      myeloperoxidase (MPO)-halide system. The H2O2-MPO-halide system in phagocytosing
      cells was localized at the fine structural level by our development of 3,3'
      diaminobenzidine (DAB) as a cytochemical probe for detecting peroxidase
      activities. Using DAB and exogenous H2O2, we confirmed that azurophil granules
      discharged MPO into the phagosome, and using particles coated with DAB and
      relying on endogenous H2O2 to yield oxidized DAB, H2O2 was localized to
      phagolysosomes. The subcellular sites of H2O2 generation were shown using cerium
      ions which react with H2O2 and precipitate electron opaque cerium perhydroxides
      (Ce(OH)2OOH and Ce(OH)3OOH). The results suggested that NADPH oxidase is
      associated with the plasma lemma, and that the enzyme enters the phagosome along
      with the invaginating plasmalemma, accounting for the presence of H2O2 in the
      phagosome. As O2.- is the major product of NADPH oxidase, its detection was of
      some importance. Based on the concept that O2.- oxidizes Mn2+ to Mn3+, and Mn3+
      oxidizes DAB, a medium containing DAB-Mn2+ was used to localize sites of O2.-
      production in stimulated PMN. The localizations were, as expected, similar to
      those for H2O2. These techniques have been of considerable usefulness and in
      general provide the foundation for cytochemistry of ROS in other systems.

PMID- 7814268
TI  - Cytochemical characterization of leucocytes from the seawater teleost, gilthead
      seabream (Sparus aurata L.).
AB  - The cytochemical characterization of head-kidney and peripheral blood leucocytes
      of gilthead seabream (Sparus aurata L.) was studied by light and electron
      microscopy. Neutrophilic granulocytes show some cytoplasmic granules, which are
      positive for alkaline phosphatase and peroxidase but acid phosphatase negative.
      The scarce granules found in the cytoplasm of the circulating neutrophils and
      their cytochemical features seem to be indicative of an immature stage.
      Acidophils are also alkaline phosphatase and peroxidase positive at pH 11.0. They
      are strongly positive for acid phosphatase and acid phosphatase activity may thus
      be considered a cytochemical marker to characterize and differentiate
      neutrophilic from acidophilic granulocytes in this fish species. Three granule
      populations are characterized in the cytoplasm of the gilthead seabream
      acidophils: the first is positive only for peroxidase and the second contains a
      dense core with acid and alkaline phosphatase activities, surrounded by a thin
      peroxidase positive electron-dense halo. The third granule type contains an
      eccentric core, which is strongly positive for acid and alkaline phosphatase and
      peroxidase. As regards their cytochemical features, the first and second granule
      types seem to correspond respectively to the azurophilic and specific granules
      found in acidophils of mammals and could be involved in phagocytic processes,
      thus playing an important microbicidal role in this species. The monocytes,
      monocyte-macrophages and macrophages show different cytochemical features. The
      first have scarce acid phosphatase-positive lysosomes, while blood monocyte
      macrophages and macrophages are positive for acid and alkaline phosphatases and
      for peroxidase; the monocyte-macrophages show scarce lysosomes.

PMID- 7814269
TI  - Enhancement of the immunocytochemical detection of antigens by microwave
      irradiation. Benefits and limitations analysed in isolated plant nuclei and
      Drosophila embryos in toto.
AB  - Performing the antibody reaction under controlled heating through microwave
      irradiation results in significant improvements in the immunovisualization of
      antigens, such as shortening the times of incubation, lowering the antibody
      titres used and allowing the detection of difficult, inaccessible antigens. In
      addition to investigate the basis of the enhancement, we have extended to more
      intact samples such as isolated plant nuclei and in toto Drosophila embryos the
      results previously reported only with tissue sections. A drop of heterologous
      anti-nucleolin antibody covering isolated nuclei from onion root meristems spread
      on a glass slide was microwave irradiated, resulting in clear immunofluorescent
      labelling of the nucleoli. This result was never previously obtained in the
      absence of microwave treatment, even using the complicated procedure previously
      reported for the homologous identification of this nuclear protein. Using the
      much larger and to some extent impermeable Drosophila embryos, we were able to
      show that the incubation time and concentration of the anti-myosin antibody can
      be strongly reduced by performing the reaction at 45 degrees C under microwave
      irradiation. The controlled increase in temperature is the main factor
      responsible for these improvements; the importance of maintaining an adequate
      mixing of the samples is also emphasized. The proper implementation of these two
      experimental conditions will require the introduction of appropriate mixing
      accessories and temperature measuring probes for samples of small volume in
      current microwave laboratory ovens.

PMID- 7814270
TI  - Surface distribution and partition during freeze-fracture of CD8 antigens on
      human lymphocytes and on epithelial transfected cells.
AB  - Freeze-fracture immunocytochemistry was used to analyse the surface distribution,
      redistribution induced by antibodies, and partition during freeze-fracture, of
      CD8 molecules on human T lymphocytes and rat epithelial transfected (FRT-U10)
      cells. Immunogold labelling of CD8 antigens was uniform over the unfractured cell
      surfaces of both lymphocytes and epithelial transfected cells. After freeze
      fracture, the gold particles were associated with the exoplasmic outer leaflets
      of the plasma membranes in both cell types. In lymphocytes, incubation with
      antibodies at 37 degrees C up to 20 min induced patching and capping of the
      antigens on the unfractured cell surface. After fracture, the patched molecules
      appeared associated with the protoplasmic inner leaflet of the plasma membranes.
      Parallel antibody-treatment at 37 degrees C of FRT-U10 cells induced clustering
      of CD8 molecules but failed to cause further aggregation in larger patches or in
      caps. After freeze-fracture, the immunolabelling was clustered, but associated
      with the exoplasmic outer leaflet of the plasma membranes as in untreated cells.
      The different redistribution induced by antibodies and the different behaviour on
      fracture of the redistributed molecules in the two cell types may be regulated by
      CD8 interaction with the cytoskeleton.

PMID- 7814272
TI  - Morphological alterations and cytoskeletal reorganization in opossum kidney (OK)
      cells during osmotic swelling and volume regulation.
AB  - Cells from a variety of tissues regulate their volume when exposed to anisotonic
      conditions. After exposure of cells to hypotonic conditions, the rapid phase of
      cell swelling is followed by a slower phase of cell shrinkage towards the initial
      volume. The present study investigates morphological alterations of adherent and
      fully spread cells after exposure to hypotonic conditions and the reorganization
      of cytoskeletal components such as F-actin, actin-binding proteins, microtubules
      and intermediate-sized filaments. We used cells of a continuous epithelial cell
      line from the opossum kidney (OK cells), which were exposed to hypotonic
      conditions for a period of 60 min at 25 degrees C. The osmolarity was reduced by
      40% from 320 mosmol/l (isotonic conditions) to 192 mosmol/l (hypotonic
      conditions). The initial swelling after exposure of OK cells to hypotonic
      conditions caused enhanced ruffling membrane activity, formation of lamellipodia
      and an extended space between adjacent cells which was caused by a more rounded
      cell shape. Moreover, the height of cells located in the centre of cell clusters
      increased by 32 +/- 8% (mean value +/- SEM) as checked by morphometric analysis
      of the vertical distance between the apical and basolateral F-actin domain.
      Although the fluorescence intensity and organization of F-actin in a horizontal
      direction remained unaltered during cell swelling, we observed a loss of
      periodicity and irregular distribution of myosin aggregates and a partial
      rearrangement of vimentin filaments in the form of short fragments. In all
      experiments the organization of microtubles was observed to be
      unaltered.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7814273
TI  - Quantification of biotinylated RNA probes for in situ hybridization using
      chemiluminescence.
AB  - For reliable detection of mRNA by non-radioactive in situ hybridization,
      calibration and standardization of the individual steps involved are essential.
      We describe a method that allows determination of the size and integrity as well
      as quantification of biotinylated RNA probes in a single experiment. Serial
      dilutions of biotinylated RNA probes generated by promoter-mediated in vitro
      transcription were size-separated by gel electrophoresis in the presence of known
      amounts of 5'-biotinylated oligomers which served as internal standard. Following
      immobilization onto nylon membranes and visualization by chemiluminescence,
      optical densities of probes and internal standards were measured by densitometry
      and analysed by linear regression. RNA probes complementary to the human homeobox
      genes HOX-C6, -C8 and -C9 were quantified. Four different 5'-biotinylated
      oligomers (20, 35, 50 and 75 bases) were tested as internal standards. Concerning
      the separation of probe and oligomer in the gel, transfer properties and
      efficiency of binding to the membrane, the oligomer of 35 bases was found to be
      the best internal standard with highest reproducibility. Comparison of probe
      concentration by spectrophotometry and the described method showed a good
      correlation, indicating that our method is a reliable assay for quantitative and
      qualitative control of biotin-labelled probes.

PMID- 7814274
TI  - Reimbursement inequities leave rural practices 'in the dust'.

PMID- 7814275
TI  - ER protocols needed for treating cardiac patients--STAT.

PMID- 7814271
TI  - Steroidogenic activity of atretic follicles in the cycling hamster ovary and
      relation to ultrastructural observations.
AB  - To evaluate the relation between the steroidogenic activity and cell
      proliferation of individual follicles in mature hamster ovaries during the
      estrous cycle, the localization of enzymes involved in estrogen biosynthesis and
      bromodeoxyuridine (BrdU) incorporation were examined immunohistochemically.
      Moreover, granulosa cells from the early atretic follicle were examined by
      scanning and transmission electron microscopy. Immunoreactivity for aromatase was
      localized in the granulosa cells of healthy developing follicles and Graafian
      follicles, as well as in newly formed granulosa lutein cells. In the healthy
      follicles of an ovulation cycle, intensity of aromatase immunoreactivity was
      suddenly decreased on day 3. The theca interna cells of healthy developing
      follicles were immunopositive for 17 alpha-hydroxylase/C17-C20 lyase (17 alpha
      lyase) from day 2 to the morning of day 4, but on the evening of day 4 most theca
      interna cells were immunonegative except for only a few cells of the large
      Graafian follicles. BrdU incorporation was observed in the granulosa cells of
      healthy developing follicles, in the endothelial cells of capillaries around the
      developing follicles, and of newly formed corpora lutea. Very early morphological
      signs of atresia was the pyknotic change of a few granulosa cells lining the
      antral cavity. In that follicle, the number of BrdU-incorporating granulosa cells
      was suddenly decreased whilst immunoreactivity of aromatase and 17 alpha-lyase
      were gradually decreased. These data suggest that the mechanism of the loss of
      aromatase activity from the granulosa cells of atretic follicles appears to
      differ from that in cycling follicles.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7814276
TI  - HIV prevention: factors that predict compliance with testing and counseling
      procedures.
AB  - Human immunodeficiency virus (HIV) testing and pretest/posttest counseling are
      central components in prevention efforts in the United States. Yet, not all
      persons return for their test results and posttest counseling. Based on an
      exploratory study at four community health centers in South Florida, the authors
      determined the percentage of patients who returned to these clinics. They also
      examined those sociodemographic and HIV antibody test-related factors that
      predicted patient return. Less than 50% of those patients tested returned.
      Younger, urban, minority group patients whose HIV serostatus was likely to be
      negative were the least likely to return for test results. The authors describe a
      direction of future research to address these disturbing findings.

PMID- 7814277
TI  - An osteopathic cardiologist's review of hypertension: beyond the Fifth Report of
      the Joint National Committee on Detection, Evaluation, and Treatment of High
      Blood Pressure.
AB  - Although hypertension was defined more than 100 years ago, it remains the leading
      cause of office visits and use of prescription drugs. Because hypertension is one
      of the major risk factors for premature death and disability, the medical
      community continues to strive toward more aggressive detection, follow-up, and
      treatment. The Fifth Report of the Joint National Committee on Detection,
      Evaluation, and Treatment of High Blood Pressure provides an excellent guide for
      all health practitioners. This publication, along with several recent articles,
      have provided a comprehensive approach to the hypertensive patient. Although
      cerebrovascular events have been dramatically reduced by the treatment of
      hypertension, results regarding cardiac morbidity and mortality have been
      disappointing. Therefore, from a cardiologists' standpoint, the concept of
      cardioprotection has evolved into an important component in the treatment of the
      hypertensive patient.

PMID- 7814278
TI  - Skewed incentives in our healthcare delivery system.
AB  - Policymakers agree that cost-containment in healthcare delivery cannot be
      attained unless the incentives for providers, patients, and payers can be
      changed. The authors review the existing incentives that have led to escalating
      costs and conflicting interests for providers, patients, employers, third-party
      payers and taxpayers. They examine the current incentives for each group and
      explore the changing incentives that the new integrated healthcare systems and
      managed care present. They conclude that the new systems are not a simplistic
      solution to the "healthcare crisis" in cost, access, and quality, but they
      emphasize that these new systems have already introduced new incentives for
      provider collaboration and cooperation. The traditional ties of the osteopathic
      medical profession allow a quick response to creating new integrated systems, but
      require collaboration to add tertiary care to the profession's strong primary
      care and community hospital base.

PMID- 7814279
TI  - Management of antibiotic-resistant pneumococcal infections.

PMID- 7814280
TI  - Ivermectin in human medicine.
AB  - Ivermectin is a potent macro-cyclic lactone causing paralysis in many nematodes
      and arthropods through an influx of chloride ions across cell membranes. It is
      currently the drug of choice for human onchocerciasis and shows potent
      microfilaricidal activity against the other major filarial parasites of human
      (Wuchereria bancrofti, Brugia malayi, Loa loa and Mansonella ozzardi) but not
      against M. perstans. Whether or not it also kills the adult-stage of these
      parasites is currently under study. Ivermectin also has excellent efficacy in
      both human strongyloidiasis and cutaneous larva migrans for which good
      alternative treatments have not been available; and it is as effective as
      currently available drugs against the intestinal nematodes Ascaris lumbricoides,
      Trichuris trichiura and Enterobius vermicularis; against the human hookworms it
      shows only partial efficacy. Preliminary studies indicate that ivermectin has the
      potential to become the drug of choice for ectoparasitic infestations (mites,
      lice) of humans as well.

PMID- 7814281
TI  - Modulation of Escherichia coli type 1 fimbrial expression and adherence to
      uroepithelial cells following exposure of logarithmic phase cells to quinolones
      at subinhibitory concentrations.
AB  - Quinolone antibiotics at sub-inhibitory concentrations have been shown to
      antagonize the adherence of Escherichia coli to urinary tract epithelium. This
      may be due either to reduced expression or to alterations to the structure of the
      fimbriae which mediate adherence. While E. coli cells in the stationary growth
      phase have previously been used to investigate quinolone-induced inhibition of
      adherence, the present study has demonstrated that bacteria in the logarithmic
      phase also produce type 1 fimbriae and that the adherence of these organisms is
      reduced following exposure to various quinolones. In all experiments, cells in
      the logarithmic phase were incubated for 3 h in the presence of ciprofloxacin,
      enoxacin, CI-960 or PD131628 at a concentration equivalent to 0.5 x MIC. An in
      vitro adherence assay which used acid-washed uroepithelial cells and a type 1
      fimbriated strain of E. coli showed reductions in adherence of 47%, 72% and 95%
      after exposure to enoxacin, ciprofloxacin and PD131628, respectively. The effects
      of ciprofloxacin, enoxacin, CI-960 and PD131628 on two phase variation
      controlling genes, fimB and fimE, and the main structural gene, fimA, were
      evaluated by quantifying beta-galactosidase production encoded by chromosomally
      located fim::lacZ fusions. All four quinolones tested caused reductions in beta
      galactosidase production by a fimA::lacZ fusion strain, but did not significantly
      affect production of this enzyme by fimB::lacZ and fimE::lacZ fusion strains;
      these agents also led to decreases in wild-type beta-galactosidase production.
      Amplification of the invertible element after exposure to enoxacin at 0.25, 0.5
      or 1 x MIC revealed no changes in orientation distribution compared with the
      antibiotic-free control. In addition, a fluorescence assay specific for type 1
      fimbriae showed only 23%, 21%, 25% and 11% reductions in the surface expression
      of the structural subunit after incubation in the presence of ciprofloxacin,
      enoxacin, CI-960 and PD131628, respectively, at 0.5 x MIC.

PMID- 7814282
TI  - Comparison of methodologies used in assessing the postantibiotic effect.
AB  - The postantibiotic effect (PAE) of the carbapenem antibiotic meropenem was
      determined for the reference strains of Escherichia coli NCTC 4174 and E. coli
      NCTC 12210. Regrowth of bacteria after antibiotic exposure was determined by
      viable counting and bioluminescence alone and in combination with an impedance
      technique and a morphological technique was also employed. Different methods of
      calculating the PAE were also used. After exposure of E. coli to 0.1-100 x MIC of
      meropenem for 2 h, concentration dependent differences in counts by
      bioluminescence, and viable counting were observed, the latter always being
      lower. The unexposed control of E. coli NCTC 4174 yielded counts of 1.1 x 10(6)
      +/- 1.1 x 10(5) and 1.3 x 10(6) +/- 4.7 x 10(5) by viable counting and
      bioluminescence respectively and E. coli NCTC 12210 gave counts of 4.2 x 10(6) +/
      1.8 x 10(6) and 1.1 x 10(7) +/- 4.3 x 10(6) by the same methods. After exposure
      to 100 x MIC of meropenem, NCTC 4174 yielded counts of 1.28 x 10(3) +/- 5.35 x
      10(2) and 2.59 x 10(5) +/- 8.61 x 10(4) and NCTC 12210 gave counts of 5.22 x
      10(3) +/- 9.74 x 10(2) and 5.21 x 10(6) +/- 1.45 x 10(6) by viable counting and
      bioluminescence, respectively. The discrepancies were due to the inability of the
      viable counting procedure to detect spheroplasts. Falsely low post exposure
      counts led to falsely low determinations of PAE by viable counting alone and in
      combination with the impedance technique.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7814283
TI  - Time-kill studies of antibiotic combinations against penicillin-resistant and 
      susceptible Streptococcus pneumoniae.
AB  - Time-kill studies were conducted to evaluate antibiotic combinations against four
      strains of Streptococcus pneumoniae for which the MICs of penicillin were 0.03,
      0.25, 1 and 4 mg/L, respectively. After 8 h of antibiotic exposure the
      combination of ceftriaxone and vancomycin showed enhanced activity against all
      four strains. Penicillin plus vancomycin and ceftriaxone plus gentamicin showed
      enhanced activity against the three penicillin-resistant strains. Combinations of
      vancomycin and rifampicin were indifferent. These results are similar to those
      found previously in the rabbit meningitis model suggesting that time-kill studies
      over 8 h may be useful in predicting in-vivo antibiotic interactions in resistant
      pneumococcal infections.

PMID- 7814284
TI  - Effect of antibiotic therapy on the antibiotic resistance of faecal Escherichia
      coli in patients attending general practitioners.
AB  - To analyse the influence of antibiotic therapy on the faecal flora of patients
      from general practice with complaints of a respiratory tract infection (RTI), 189
      paired faecal specimens were collected, before and after completing antibiotic
      treatment (n = 129) and symptomatic treatment (n = 60). Faecal specimens were
      examined for the prevalence and degree of resistance to amoxycillin, apramycin,
      ciprofloxacin, nalidixic acid, neomycin, nitrofurantoin, oxytetracycline,
      sulphamethoxazole and trimethoprim. In the antibiotic-treated group a significant
      increase in the prevalence of resistance to amoxycillin post-treatment from 50%
      to 64% (P < 0.05, Wilcoxon) was observed. In the symptomatic treated group no
      significant differences in the prevalence of resistance were found. Using
      discriminant analysis, amoxycillin and doxycycline therapy contributed to an
      increased prevalence of resistance to amoxycillin and oxytetracycline,
      respectively. In the antibiotic-treated group Escherichia coli isolates post
      treatment had a significantly increased resistance rate to amoxycillin (15%-23%)
      and to neomycin (2%-6%) (P < 0.05, Wilcoxon). Logistic regression analysis showed
      a cross resistance to neomycin and kanamycin, and for kanamycin cross-resistance
      to apramycin, neomycin and streptomycin occurred.

PMID- 7814285
TI  - Multiple dose pharmacokinetics of an oral solution of itraconazole in autologous
      bone marrow transplant recipients.
AB  - The pharmacokinetics of itraconazole oral solution were measured in seven
      patients receiving chemotherapy followed by autologous bone marrow
      transplantation for leukaemia or lymphoma. Patients received 5 mg/kg/day
      itraconazole either as a once or twice daily dose. Drug concentrations reached
      steady state by day 15, in both groups. The mean pre-dose itraconazole serum
      concentration at hour 0, day 8 was 385 ng/mL in the od group and 394 ng/mL in the
      bd group, rising to 762 and 845 ng/mL by day 15, respectively. The mean AUCs for
      0-24 h on day 8, 15 and 22 were 17,310 and 13,302 ng/mL/h, 24,476 and 25,154 and
      22,621 and 21,423, for the od and bd groups, respectively. Thus serum
      concentrations of itraconazole suitable for antifungal prophylaxis can be
      attained in neutropenic patients, with the administration of an oral solution in
      a dosage of 5 mg/kg as either an od or bd schedule, following pre-autograft high
      dose cytotoxic chemotherapy.

PMID- 7814286
TI  - Antibiotic resistance patterns and plasmid profiles for Shigella spp. isolated in
      Cordoba, Argentina.
AB  - The antimicrobial resistance patterns and plasmid profile analyses for 30
      Shigella spp. isolated in Cordoba, Argentina, were determined. Most strains were
      resistant to multiple antibiotics, particularly traditional agents such as
      ampicillin, chloramphenicol and trimethoprim. All isolates harboured at least one
      plasmid (range 1-12), the plasmid profiles differing in every case. Nineteen
      strains transferred all or some of their resistance determinants by conjugation.

PMID- 7814287
TI  - In-vitro activity of new sulphanilil fluoroquinolones against Staphylococcus
      aureus.
AB  - Two new quinolones, NSFQ-104 and NSFQ-105, derivatives of ciprofloxacin and
      norfloxacin with a 4-(4-aminophenylsulphonyl)-1-piperazinyl at position 7 showed
      better in-vitro activity against strains of methicillin-susceptible and
      methicillin-resistant Staphylococcus aureus than ciprofloxacin or norfloxacin.
      Their in-vitro activity was enhanced at pH 5.5.

PMID- 7814288
TI  - Absence of toxicity in patients with malignant otitis externa following long-term
      treatment with high dosage tobramycin.
AB  - An in-vitro model of aminoglycoside dosing was used to demonstrate that the
      bactericidal activity of tobramycin against Pseudomonas aeruginosa is directly
      related to the peak concentration of the drug. In addition, six patients who were
      being treated for malignant otitis externa with long-term, high dosage tobramycin
      were monitored for oto- and nephro-toxicity; the only adverse effects were
      transient increases in the serum creatinine concentration in two patients.

PMID- 7814289
TI  - Antibiotic susceptibility of invasive and non-invasive isolates of Haemophilus
      influenzae from the Gambia, west Africa.

PMID- 7814290
TI  - Suppressive effect of clindamycin on development of beta-lactam resistance in
      Enterobacter cloacae ATCC 23355.

PMID- 7814291
TI  - Antiviral activity of famciclovir and acyclovir in mice infected
      intraperitoneally with herpes simplex virus type 1 SC16.

PMID- 7814293
TI  - Prophylaxis after splenectomy.

PMID- 7814294
TI  - Effects of zinc concentration on the imipenemase activity of a metallo-beta
      lactamase from a Bacteroides fragilis clinical isolate.

PMID- 7814292
TI  - Salmonella gastroenteritis: longterm follow-up of an outbreak after treatment
      with norfloxacin or co-trimoxazole.

PMID- 7814295
TI  - Susceptibility of enterococci to ciprofloxacin.

PMID- 7814296
TI  - In-vitro activity of ampicillin/sulbactam against multiresistant Acinetobacter
      calcoaceticus var. anitratus clinical isolates.

PMID- 7814297
TI  - The serum concentrations of desmethyl ofloxacin and ofloxacin N-oxide in
      seriously ill patients and their possible contributions to the antibacterial
      activity of ofloxacin.

PMID- 7814298
TI  - Clinical response to the addition of clarithromycin in Pneumocystis carinii
      pneumonia refractory to high dose co-trimoxazole.

PMID- 7814299
TI  - Effects of membrane lipid peroxidation by tert butyl hydroperoxide on the sodium
      current in isolated feline ventricular myocytes.
AB  - Membrane lipid peroxidation is known to play a pivotal role in the genesis of
      coronary reperfusion arrhythmias in both experimental and clinical settings. To
      elucidate the electrophysiological mechanisms underlying these arrhythmias, the
      effects of tert butyl hydroperoxide (TBH) on the Na+ current (INa) in isolated
      feline ventricular myocytes were studied using whole-cell patch clamp techniques
      under 100% O2 bubbling. This agent at 20 mM inhibited INa from 2.2 +/- 1.3 to 1.7
      +/- 1.0 nA (P < 0.01, n = 7) without changing time courses of INa inactivation.
      Twenty millimoles TBH shifted the steady-state inactivation curve for INa from 
      77.4 +/- 1.7 to -81.3 +/- 1.8 mV when measured at INa half inhibition voltage (P
      < 0.01, n = 7), but did not affect the slope factor. The kinetics of INa recovery
      from inactivation remained unchanged. These findings suggest that lipid
      peroxidation in the membrane by TBH reduces INa conductance and voltage-dependent
      INa availability, most likely as a result of structural damage to the Na+
      channels.

PMID- 7814301
TI  - Long-term clinical effect of nilvadipine in patients with chronic heart failure:
      a double-blind placebo-controlled study.
AB  - The long-term effect of calcium channel blockers on chronic heart failure is
      disappointing, probably because of reflex sympathetic activation through arterial
      vasodilation. However, nilvadipine may be beneficial for treatment of chronic
      heart failure since this drug has minimal effects on sympathetic activation. In
      this study, the effects of 12-week administration of nilvadipine or placebo on
      symptoms of heart failure and cardiac function were investigated in 23 patients
      with mild-to-moderate chronic heart failure in a double-blind trial. The patients
      were randomly assigned to either a nilvadipine group (16 mg daily) or a placebo
      group. Intergroup comparisons did not show significant differences in any
      parameters. Serious adverse effects were not observed during the study. Thus,
      this study failed to show any beneficial effect of nilvadipine in the long-term
      treatment of patients with chronic heart failure. We conclude that the long-term
      administration of nilvadipine (16 mg daily) is neither effective nor harmful in
      the treatment of patients with chronic heart failure.

PMID- 7814302
TI  - Myocardial contrast echocardiography of coronary artery lesions due to Kawasaki
      disease.
AB  - In addition to coronary arteriography, myocardial contrast echocardiography (MCE)
      was performed in 25 patients with coronary artery lesions due to Kawasaki
      disease, in order to investigate its validity in the evaluation of these lesions
      and its safety in children. The patients' ages ranged from 1.0 to 15.9 years
      (mean, 8.6 years). Their coronary artery lesions included occlusion in 9 branches
      (9 patients), segmental stenosis in 9 (8 patients), localized stenosis in 16 (12
      patients), and dilated lesions without coexistent stenotic lesions in 5 patients.
      Seven patients had coronary artery bypass grafts. Myocardial perfusion patterns
      of the stenotic lesions and coronary artery bypass grafts could be clearly
      demonstrated by MCE. For the assessment of safety, electrocardiograms obtained at
      the time of MCE and coronary arteriography in 14 patients showed no significant
      difference in the findings between MCE and coronary arteriography. Serum glutamic
      oxaloacetic transaminase, glutamic pyruvic transaminase, lactic dehydrogenase,
      and creatine phosphokinase levels were measured before and 1 day after the
      procedure in 14 patients who underwent MCE and coronary arteriography, and in a
      group of 14 patients who underwent coronary arteriography alone. No significant
      difference was noted between the values of the two groups. These results
      suggested that MCE can be utilized in the assessment of coronary artery lesions
      due to Kawasaki disease, and confirmed the safety of the procedure even in young
      children.

PMID- 7814303
TI  - Pulmonary arterial changes in patients dying after a modified Fontan procedure
      following pulmonary artery banding.
AB  - Pulmonary arterial changes were histometrically analyzed in four cases of
      postoperative death following a modified Fontan procedure in which pulmonary
      artery banding had previously been performed because of pulmonary hypertension.
      Case 1 was a 3-year-old girl with corrected transposition of the great arteries
      (TGA), ventricular septal defect, and double-inlet left ventricle; case 2 was a 6
      year-old girl with single ventricle (SV) and complete TGA; case 3 was a 25-month
      old boy with SV and double-outlet right ventricle; and case 4 was a 21-year-old
      man with tricuspid atresia. The cause of death in cases 1, 2, and 3 was pulmonary
      hypertensive crisis due to postoperative vasoconstriction of the small pulmonary
      arteries. Medical hypertrophy remained in half of the preacinar small pulmonary
      arteries although it was not observed in all the intraacinar arteries in cases 1
      and 2, even after banding. The postoperative course of case 4 was uneventful
      despite multiple thromboembolism in the small pulmonary arteries. However, the
      patient died due to a thrombosed artificial valve. The results suggest that
      residual medial hypertrophy of the small pulmonary arteries was a major risk
      factor in these cases. Lung biopsy is recommended to determine the indications
      for the Fontan procedure in these hemodynamically critical cases.

PMID- 7814300
TI  - Functional 5-HT receptor subtypes in the isolated canine common carotid artery.
AB  - The vascular responses to 5-hydroxytrypamine (5-HT), 5-carboxamidotryptamine (5
      CT, a selective 5-HT1-like receptor agonist), alpha-methyl-5-HT (alpha-M-5-HT, a
      relatively selective 5-HT2 receptor agonist), noradrenaline (NA), and KCl were
      examined in isolated, cannulated, and perfused canine common carotid arterial
      preparations. They caused strong vasoconstrictions. The rank order of
      vasoconstrictive potency was 5-HT > alpha-M-5-HT > or = NA > 5-CT >> KCl. The 5
      HT-induced vasoconstriction was significantly depressed by methysergide (a 5-HT1
      and 5-HT2 receptor antagonist), ketanserin (a selective 5-HT2 receptor
      antagonist), and spiperone (a selective 5-HT2 receptor antagonist). The 5-CT- and
      alpha-M-5-HT-induced vasoconstrictions were also significantly inhibited by
      methysergide, spiperone, and ketanserin. The NA-induced vasoconstriction was
      readily inhibited by bunazosin (an alpha-adrenoceptor antagonist) and ketanserin
      but not significantly inhibited by spiperone and methysergide. KCl has a weak
      potency for producing a vasoconstriction of the canine common carotid artery. A
      relatively large dose of diltiazem (a calcium channel-blocker) did not modify 5
      HT-induced vasoconstrictions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7814304
TI  - Left ventricular diastolic pulsus alternans in hypertrophic cardiomyopathy.
AB  - We examined left ventricular (LV) diastolic pulsus alternans associated with
      systolic pulsus alternans in a patient with hypertrophic cardiomyopathy.
      Alternation in abnormal LV diastolic pressure waveforms persistently declining
      into mid-diastole (incomplete relaxation) and normal diastolic pressure were
      noted. Diastolic pulsus alternans was not corrected by isoproterenol and may
      possibly be independent of systolic pulsus alternans.

PMID- 7814305
TI  - The path to care in autism: is it better now?
AB  - Parents of children with autism often report problems associated with obtaining a
      diagnosis of their child's condition, family support, information, and
      appropriate services. To evaluate any changes in the situation over the last two
      decades, the families of all members of the West Midlands Autistic Society, age
      19 years and below, were asked to fill in a questionnaire that covered aspects of
      detection, diagnosis, help and information received, and educational provision.
      Responses were obtained from 127 families, the children of whom formed an older
      group ages 10 years and above (n = 67) and a younger group ages 9 years and below
      (n = 61). Findings show that there have been improvements for the younger group
      in some areas, such as earlier referral, diagnosis, and statementing. However,
      the situation with respect to advice given by professionals and the support and
      provision available after referral is still much the same as that experienced by
      families of the older group of children. Many difficulties and hurdles remain
      which hinder parents and children on the path to care in autism.

PMID- 7814306
TI  - Vigorous, aerobic exercise versus general motor training activities: effects on
      maladaptive and stereotypic behaviors of adults with both autism and mental
      retardation.
AB  - Examined the effects of antecedent exercise conditions on maladaptive and
      stereotypic behaviors in 6 adults with both autism and moderate to profound
      mental retardation. The behaviors were observed in a controlled environment
      before and after 2 exercise and 1 non-exercise conditions. From the original
      group of 6 participants, 2 were selected subsequently to participate in aerobic
      exercise immediately before performing a community-integrated vocational task.
      Only antecedent aerobic exercise significantly reduced maladaptive and
      stereotypic behaviors in the controlled setting. Neither of the less vigorous
      antecedent conditions did. When aerobic exercise preceded the vocational task,
      similar reductions were observed. There were individual differences in response
      to antecedent exercise. Use of antecedent aerobic exercise to reduce maladaptive
      and stereotypic behaviors of adults with both autism and mental retardation is
      supported.

PMID- 7814307
TI  - A second look at second-order belief attribution in autism.
AB  - Compared the performance of autistic and mentally retarded subjects, all of whom
      had passed a standard first-order test of false belief, on a new second-order
      belief task. 12 autistic and 12 mentally retarded subjects, matched on verbal
      mental age (assessed by PPVT and a sentence comprehension subtest of the CELF)
      and full-scale IQ were given two trials of a second-order reasoning task which
      was significantly shorter and less complex than the standard task used in all
      previous research. The majority of subjects in both groups passed the new task,
      and were able to give appropriate justifications to their responses. No group
      differences were found in performance on the control or test questions. Findings
      are interpreted as evidence for the role of information processing factors rather
      than conceptual factors in performance on higher order theory of mind tasks.

PMID- 7814308
TI  - Affective disorders in people with autism: a review of published cases.
AB  - The presentation of affective disorders in people with autism and autistic-like
      disorders is discussed based upon a review of 17 published cases. Half of the
      patients were female and almost all of the patients had IQs in the mentally
      retarded range. 35% of the patients had the onset of affective disorder in
      childhood. Of the cases mentioning family history, 50% had a family history of
      affective disorder or suicide. Changes in mood, self-attitude, and vital sense
      were rarely reported by the patients. A change in mood, attitude toward self and
      others, and vegetative changes were inferred based on the observations of others.
      Difficulties in diagnosing affective disorders in autistic people are presented
      and suggestions are made for diagnosis, treatment, and research.

PMID- 7814309
TI  - An observational study of humor in autism and Down syndrome.
AB  - Investigated examples of naturalistic humor in a group of 6 young children with
      autism and 6 age- and language-matched children with Down syndrome, who were
      videotaped while interacting with their mothers in bimonthly 1-hour sessions over
      the course of 1 year. Humor episodes were analyzed on three dimensions: cognitive
      developmental, social, and intentionality. The autistic children produced
      significantly less humor overall and less humor involving nonverbal incongruity.
      The only jokes in the study were told by 2 of the children with Down syndrome.
      Results indicate that while children with autism can produce and appreciate humor
      to a limited extent in a naturalistic setting, they do so at a significantly
      reduced level compared to matched controls. Findings are discussed in relation to
      the social-cognitive deficits in autistic children, which are among the primary
      characteristics of the syndrome.

PMID- 7814310
TI  - Behavioral medicine treatment of ruminative vomiting and associated weight loss
      in an adolescent with autism.
AB  - Treated persistent ruminative vomiting of a 15-year-old boy with autism using a
      multicomponent behavioral medicine program within a residential facility.
      Preceding intervention the boy had lost 15 pounds associated with high-rate
      ruminating. The treatment program included a combination of dietary, nutritional,
      and behavioral procedures that emphasized food restrictions, satiation, and
      setting condition manipulations. Ruminative vomiting was reduced to near-zero
      levels and weight gain was achieved following treatment implementation. These
      therapeutic gains were sustained during a maintenance programming phase and at 1-
      through 4-month follow-up assessments. Issues related to functional assessment
      and treatment formulation in behavioral medicine intervention for ruminative
      vomiting are discussed.

PMID- 7814311
TI  - Increasing opportunities for requesting in classrooms serving children with
      developmental disabilities.
AB  - Evaluated an intervention package for increasing requesting opportunities in
      special education classrooms. Five teachers, serving 26 children with moderate to
      severe disabilities, received in-service training, consultation, and feedback on
      the use of three strategies designed to create opportunities for requesting
      (i.e., missing item, interrupted chain, delayed assistance). Observations were
      conducted in a multiple-baseline across classrooms design to record the number
      and types of opportunities provided by each teacher. During baseline, few
      opportunities for requesting were observed. The number of opportunities for
      requesting and the number of correct student responses increased during
      intervention. Opportunities continued to be provided during generalization and
      follow-up sessions. The study demonstrated an effective strategy for helping
      teachers incorporate opportunities for functional communication into the natural
      environment.

PMID- 7814312
TI  - A naturalistic approach to the validation of facilitated communication.
AB  - By manipulating the facilitator's knowledge of a student's just-completed
      activity, facilitated communication ability and the extent of guiding were
      assessed. Seven students diagnosed with mental retardation and their facilitators
      participated in the study. All 7 students were purported at the start of the
      study to be communicating via facilitation at levels far above what was
      previously thought possible given their level of intellectual ability. A large
      degree of facilitator guiding was revealed for each of the 4 facilitators.
      Minimal evidence of facilitation was found for 4 of the 7 students. One of the 7
      students demonstrated validated facilitated communication on two trials.

PMID- 7814313
TI  - Autism Diagnostic Interview-Revised: a revised version of a diagnostic interview
      for caregivers of individuals with possible pervasive developmental disorders.
AB  - Describes the Autism Diagnostic Interview-Revised (ADI-R), a revision of the
      Autism Diagnostic Interview, a semistructured, investigator-based interview for
      caregivers of children and adults for whom autism or pervasive developmental
      disorders is a possible diagnosis. The revised interview has been reorganized,
      shortened, modified to be appropriate for children with mental ages from about 18
      months into adulthood and linked to ICD-10 and DSM-IV criteria. Psychometric data
      are presented for a sample of preschool children.

PMID- 7814314
TI  - Brief report: an autistic male presenting seasonal affective disorder (SAD) and
      trichotillomania.

PMID- 7814315
TI  - Catabolic and anabolic enzyme activities and energetics of acetone metabolism of
      the sulfate-reducing bacterium Desulfococcus biacutus.
AB  - Acetone degradation by cell suspensions of Desulfococcus biacutus was CO2
      dependent, indicating initiation by a carboxylation reaction, while degradation
      of 3-hydroxybutyrate was not CO2 dependent. Growth on 3-hydroxybutyrate resulted
      in acetate accumulation in the medium at a ratio of 1 mol of acetate per mol of
      substrate degraded. In acetone-grown cultures no coenzyme A (CoA) transferase or
      CoA ligase appeared to be involved in acetone metabolism, and no acetate
      accumulated in the medium, suggesting that the carboxylation of acetone and
      activation to acetoacetyl-CoA may occur without the formation of a free
      intermediate. Catabolism of 3-hydroxybutyrate occurred after activation by CoA
      transfer from acetyl-CoA, followed by oxidation to acetoacetyl-CoA. In both
      acetone-grown cells and 3-hydroxybutyrate-grown cells, acetoacetyl-CoA was
      thioyltically cleaved to two acetyl-CoA residues and further metabolized through
      the carbon monoxide dehydrogenase pathway. Comparison of the growth yields on
      acetone and 3-hydroxybutyrate suggested an additional energy requirement in the
      catabolism of acetone. This is postulated to be the carboxylation reaction (delta
      G(o)' for the carboxylation of acetone to acetoacetate, +17.1 kJ.mol-1). At the
      intracellular acyl-CoA concentrations measured, the net free energy change of
      acetone carboxylation and catabolism to two acetyl-CoA residues would be close to
      0 kJ.mol of acetone-1, if one mol of ATP was invested. In the absence of an
      energy-utilizing step in this catabolic pathway, the predicted intracellular
      acetoacetyl-CoA concentration would be 10(13) times lower than that measured.
      Thus, acetone catabolism to two acetyl-CoA residues must be accompanied by the
      utilization of teh energetic equivalent of (at lease) one ATP molecule.
      Measurement of enzyme activities suggested that assimilation of acetyl-CoA
      occurred through a modified citric acid cycle in which isocitrate was cleaved to
      succinate and glyoxylate. Malate synthase, condensing glyoxylate and acetyl-CoA,
      acted as an anaplerotic enzyme. Carboxylation of pyruvate of phosphoenolpyruvate
      could not be detected.

PMID- 7814316
TI  - Two Lactococcus lactis genes, including lacX, cooperate to trigger an SOS
      response in a recA-negative background.
AB  - A 4.3-kb EcoRI fragment from a Lactococcus lactis genomic library alleviates the
      methyl methanesulfonate, mitomycin C, and UV sensitivities of an Escherichia coli
      recA mutant (M. Novel, X. F. Huang, and G. Novel, FEMS Microbiol. Lett. 72:309
      314, 1990). It complements recA1 and delta recA mutations but not recA13. Three
      proteins (with molecular masses of 20, 35, and 23 kDa) were produced from this
      fragment in a T7-directed system, and three corresponding genes were detected by
      DNA sequencing, namely, ISS1CH;lacX, which is the distal gene of the lac operon;
      and a third open reading frame, named lacN, which encodes 211 amino acids.
      Mutations produced in either lacX or in lacN resulted in the loss of the
      resistance to DNA-damaging agents. Thus, these two genes appeared to be involved
      in this activity. Introduction of pUCB214 carrying the 4.3-kb fragment into a
      lexA+ delta recA306 sfiA::lacZ strain resulted in UV-inducible synthesis of beta
      galactosidase. A uvrA strain or a lexA (Ind-) strain containing pUCB214 did not
      support any DNA repair. However, a lexA (Def-) strain carrying pUCB214 could
      partly repair UV damage. We discuss possible targets for LacX and LacN products,
      and we speculate that LacX and LacN may constitute a two-component regulatory
      system that is able to respond to SOS signals, and then to act in the SOS
      response, bypassing the RecA-activated function.

PMID- 7814317
TI  - Identification and characterization of two nitrogen-regulated genes of the
      cyanobacterium Synechococcus sp. strain PCC7942 required for maximum efficiency
      of nitrogen assimilation.
AB  - Two nitrogen-regulated genes were found in the genomic DNA region upstream of the
      nirA operon involved in uptake and utilization of nitrate in Synechococcus sp.
      strain PCC7942. The two genes (nirB and ntcB) are transcribed divergently from
      nirA and encode proteins of 349 and 309 amino acid residues, respectively. The
      levels of nirB and ntcB transcripts were low in cells growing on ammonium and
      increased upon transfer of ammonium-grown cells to nitrate-containing medium. The
      deduced NirB protein sequence has no similarities to other known proteins,
      whereas the deduced NtcB protein sequence is homologous to bacterial
      transcriptional activators of the LysR family. Defined mutants constructed by
      interrupting nirB or ntcB with a drug resistance marker grew as fast as the wild
      type strain on ammonium but grew slower than the wild-type strain on nitrate or
      nitrite. The nirB mutant had higher activities of nitrate reductase, glutamine
      synthetase, and glutamate synthase than the wild-type strain, but its nitrite
      reductase activity was 40% of the wild-type levels. The mutant excreted nitrite
      into the medium during growth on nitrate, showing that nitrite reductase limits
      nitrate assimilation. These findings suggested that nirB is required for
      expression of maximum nitrite reductase activity. When grown on ammonium, the
      nirB mutant grew normally but cultures of the ntcB mutant still showed a
      yellowish-green color typical of nitrogen-limited cells. NtcB seems to regulate
      utilization of fixed nitrogen by controlling the expression of a certain gene(s)
      involved in nitrogen metabolism.

PMID- 7814318
TI  - Membrane topology analysis of Escherichia coli K-12 Mtr permease by alkaline
      phosphatase and beta-galactosidase fusions.
AB  - The mtr gene of Escherichia coli K-12 encodes an inner membrane protein which is
      responsible for the active transport of trypotophan into the cell. It has been
      proposed that the Mtr permease has a novel structure consisting of 11 hydrophobic
      transmembrane spans, with a cytoplasmically disposed amino terminus and a
      carboxyl terminus located in the periplasmic space (J.P. Sarsero, P. J. Wookey,
      P. Gollnick, C. Yanofsky, and A.J. Pittard, J. Bacteriol. 173:3231-3234, 1991).
      The validity of this model was examined by the construction of fusion proteins
      between the Mtr permease and alkaline phosphatase or beta-galactosidase. In
      addition to the conventional methods, in which the reporter enzyme replaces a
      carboxyl-terminal portion of the membrane protein, the recently developed
      alkaline phosphatase sandwich fusion technique was utilized, in which alkaline
      phosphatase is inserted into an otherwise intact membrane protein. A cluster of
      alkaline phosphatase fusions to the carboxyl-terminal end of the Mtr permease
      exhibited high levels of alkaline phosphatase activity, giving support to the
      proposition of a periplasmically located carboxyl terminus. The majority of
      fusion proteins produced enzymatic activities which were in agreement with the
      positions of the fusion sites on the proposed topological model of the permease.
      The synthesis of a small cluster of hybrid proteins, whose enzymatic activity did
      not agree with the location of their fusion sites within putative transmembrane
      span VIII or the preceding periplasmic loop, was not detected by immunological
      techniques and did not necessitate modification of the proposed model in this
      region. Slight alterations may need to be made in the positioning of the carboxyl
      terminal end of transmembrane span X.

PMID- 7814320
TI  - Maleylacetate reductase of Pseudomonas sp. strain B13: specificity of substrate
      conversion and halide elimination.
AB  - Maleylacetate reductase (EC 1.3.1.32) plays a major role in the degradation of
      chloroaromatic compounds by channelling maleylacetate and some chlorinated
      derivatives into the 3-oxoadipate pathway. Several substituted maleylacetates
      were prepared in situ by alkaline or enzymatic hydrolysis of dienelactones as the
      precursor. The conversion of these methyl-, chloro-, fluoro-, and bromo
      substituted maleylacetates by malelacetate reductase from 3-chlorobenzoate-grown
      cells of Pseudomonas sp. strain B13 was studied. Two moles of NADH per mole of
      substrate was consumed for the conversion of maleylacetates which contain a
      halogen substituent in the 2 position. In contrast, only 1 mol of NADH was
      necessary to convert 1 mol of substrates without a halogen substituent in the 2
      position. The conversion of 2-fluoro-, 2-chloro-, 2,3-dichloro-, 2,5-dichloro-,
      2,3,5-trichloro-, 2-bromo-, 2,3-dibromo-, 2,5-dibromo-, 2-bromo-5-chloro-, 2
      chloro-3-methyl-, and 2-chloro-5-methylmaleylacetate was accompanied by the
      elimination of halide from the 2 position and the temporary occurrence of the
      corresponding dehalogenated maleylacetate as an intermediate consuming the second
      mole equivalent of NADH. The properties of the halogen substituents influenced
      the affinity to the enzyme in the following manner. Km values increased with
      increasing van der Waals radii and with decreasing electronegativity of the
      halogen substituents (i.e., low steric hindrance and high electronegativity
      positively influenced the binding). The Km values obtained with 2-methyl-,3
      methyl-, and 5-methylmaleylacetate showed that a methyl substituent negatively
      affected the affinity in the following order: 2 position >/ = 3 position >> 5
      position. A reaction mechanism explaining the exclusive elimination of halogen
      substituents from the 2 position is proposed.

PMID- 7814319
TI  - Nucleotide sequence and genetic analysis of the neuD and neuB genes in region 2
      of the polysialic acid gene cluster of Escherichia coli K1.
AB  - The K1 capsular polysaccharide, a polymer of sialic acid, is an important
      virulence determinant of extraintestinal pathogenic Escherichia coli. The genes
      responsible for the synthesis and expression of the polysialic acid capsule of E.
      coli K1 are located on the 17-kb kps gene cluster, which is functionally divided
      into three regions. Central region 2 encodes proteins necessary for the
      synthesis, activation, and polymerization of sialic acid, while flanking regions
      1 and 3 are involved in polymer transport to the cell surface. In this study, we
      identified two genes at the proximal end of region 2, neuD and neuB, which encode
      proteins with predicted sizes of 22.7 and 38.7 kDa, respectively. Several
      observations suggest that the neuB gene encodes sialic acid synthase. EV24, a
      neuB chromosomal mutant that expresses a capsule when provided exogenous sialic
      acid, could be complemented in trans by the cloned neuB gene. In addition, NeuB
      has significant sequence similarity to the product of the cpsB gene of Neisseria
      meningitidis group B, which is postulated to encode sialic acid synthase. We also
      present data indicating that neuD has an essential role in K1 polymer production.
      Cells harboring pSR426, which contains all of region 2 but lacks region 1 and 3
      genes, produce an intracellular polymer. In contrast, no polymer accumulated in
      cells carrying a derivative of pSR426 lacking a functional neuD gene. Unlike
      strains with mutations in neuB, however, neuD mutants are not complemented by
      exogenous sialic acid, suggesting that NeuD is not involved in sialic acid
      synthesis. Additionally, cells harboring a mutation in neuD accumulated sialic
      acid and CMP-sialic acid. We also found no significant differences between the
      endogenous and exogenous sialyltransferase activities of a neuD mutant and the
      wild-type organism. NeuD shows significant similarity to a family of bacterial
      acetyltransferases, leading to the theory that NeuD is an acetyltransferase which
      may exert its influences through modification of other region 2 proteins.

PMID- 7814321
TI  - Cloning, nucleotide sequence, and mutagenesis of the Bacillus subtilis ponA
      operon, which codes for penicillin-binding protein (PBP) 1 and a PBP-related
      factor.
AB  - An oligonucleotide probe designed to hybridize to genes encoding class A high
      molecular-weight penicillin-binding proteins (PBPs) was used to identify the ponA
      gene encoding PBP1a and -1b (PBP1) of Bacillus subtilis. The identity of the ponA
      product was established by (i) the presence of a sequence coding for a peptide
      generated from PBP1 and (ii) the disappearance of PBP1 in a ponA mutant. DNA
      sequence analysis revealed that the amino acid sequence of PBP1 was similar to
      those of other class A high-molecular-weight PBPs and that ponA appeared to be
      cotranscribed with an upstream gene (termed prfA) of unknown function. Null
      mutations in ponA resulted in a slight decrease in growth rate and a change in
      colony morphology but had no significant effect on cell morphology, cell
      division, sporulation, spore heat resistance, or spore germination. Mutations in
      prfA which did not effect ponA expression produced a more significant decrease in
      growth rate but had no other significant phenotypic effects. Deletion of both
      prfA and ponA resulted in extremely slow growth and a reduction in sporulation
      efficiency. Studies of expression of transcriptional fusions of ponA and prfA to
      lacZ demonstrated that these two genes constitute an operon. Expression of these
      genes was relatively constant during growth, decreased during sporulation, and
      was induced approximately 15 min into spore germination. The ponA locus was
      mapped to the 200 degrees region of the chromosomal physical map.

PMID- 7814322
TI  - Staphylococcus haemolyticus contains two D-glutamic acid biosynthetic activities,
      a glutamate racemase and a D-amino acid transaminase.
AB  - Two D-glutamic acid biosynthetic activities, glutamate racemase and D-amino acid
      transaminase, have been described previously for bacteria. To date, no bacterial
      species has been reported to possess both activities. Genetic complementation
      studies using Escherichia coli WM335, a D-glutamic acid auxotroph, and cloned
      chromosomal DNA fragments from Staphylococcus haemolyticus revealed two distinct
      DNA fragments containing open reading frames which, when present, allowed growth
      on medium without exogenous D-glutamic acid. Amino acid sequences of the two open
      reading frames derived from the DNA nucleotide sequences indicated extensive
      identity with the amino acid sequence of Pediococcus pentosaceous glutamate
      racemase in one case and with that of the D-amino acid transaminase of Bacillus
      spp. in the second case. Enzymatic assays of lysates of E. coli WM335 strains
      containing either the cloned staphylococcal racemase or transminase verified the
      identities of these activities. Subsequent DNA hybridization experiments
      indicated that Staphylococcus aureus, in addition to S. haemolyticus, contained
      homologous chromosomal DNA for each of these genes. These data suggest that S.
      haemolyticus, and probably S. aureus, contains genes for two D-glutamic acid
      biosynthetic activities, a glutamate racemase (dga gene) and a D-amino acid
      transaminase (dat gene).

PMID- 7814324
TI  - Isolation and characterization of mutants impaired in the selective degradation
      of peroxisomes in the yeast Hansenula polymorpha.
AB  - We have isolated a collection of peroxisome degradation-deficient (Pdd-) mutants
      of the yeast Hansenula polymorpha which are impaired in the selective autophagy
      of alcohol oxidase-containing peroxisomes. Two genes, designated PDD1 and PDD2,
      have been identified by complementation and linkage analyses. In both mutant
      strains, the glucose-induced proteolytic turnover of peroxisomes is fully
      prevented. The pdd1 and pdd2 mutant phenotypes were caused by recessive monogenic
      mutations. Mutations mapped in the PDD1 gene appeared to affect the initial step
      of peroxisome degradation, namely, sequestration of the organelle to be degraded
      by membrane multilayers. Thus, Pdd1p may be involved in the initial signalling
      events which determine which peroxisome will be degraded. The product of the PDD2
      gene appeared to be essential for mediating the second step in selective
      peroxisome degradation, namely, fusion and subsequent uptake of the sequestered
      organelles into the vacuole. pdd1 and pdd2 mutations showed genetic interactions
      which suggested that the corresponding gene products may physically or
      functionally interact with each other.

PMID- 7814323
TI  - Caulobacter FliQ and FliR membrane proteins, required for flagellar biogenesis
      and cell division, belong to a family of virulence factor export proteins.
AB  - The Caulobacter crescentus fliQ and fliR genes encode membrane proteins that have
      a role in an early step of flagellar biogenesis and belong to a family of
      proteins implicated in the export of virulence factors. These include the MopD
      and MopE proteins from Erwinia carotovora, the Spa9 and Spa29 proteins from
      Shigella flexneri, and the YscS protein from Yersinia pestis. Inclusion in this
      family of proteins suggests that FliQ and FliR may participate in an export
      pathway required for flagellum assembly. In addition, mutations in either fliQ or
      fliR exhibit defects in cell division and thus may participate directly or
      indirectly in the division process. fliQ and fliR are class II flagellar genes
      residing near the top of the regulatory hierarchy that determines the order of
      flagellar gene transcription. The promoter sequence of the fliQR operon differs
      from most known bacterial promoter sequences but is similar to other Caulobacter
      class II flagellar gene promoter sequences. The conserved nucleotides in the
      promoter region are clustered in the -10, -20 to -30, and -35 regions. The
      importance of the conserved bases for promoter activity was demonstrated by
      mutational analysis. Transcription of the fliQR operon is initiated at a specific
      time in the cell cycle, and deletion analysis revealed that the minimal sequence
      required for transcriptional activation resides within 59 bp of the start site.

PMID- 7814325
TI  - Characterization of a mutant strain of Saccharomyces cerevisiae with a deletion
      of the RAD27 gene, a structural homolog of the RAD2 nucleotide excision repair
      gene.
AB  - We have constructed a strain of Saccharomyces cerevisiae with a deletion of the
      YKL510 open reading frame, which was initially identified in chromosome XI as a
      homolog of the RAD2 nucleotide excision repair gene (A. Jacquier, P. Legrain, and
      B. Dujon, Yeast 8:121-132, 1992). The mutant strain exhibits increased
      sensitivity to UV light and to the alkylating agent methylmethane sulfonate but
      not to ionizing radiation. We have renamed the YKL510 open reading frame the
      RAD27 gene, in keeping with the accepted nomenclature for radiation-sensitive
      yeast mutants. Epistasis analysis indicates that the gene is in the RAD6 group of
      genes, which are involved in DNA damage tolerance. The mutant strain also
      exhibits increased plasmid loss, increased spontaneous mutagenesis, and a
      temperature-sensitive lethality whose phenotype suggests a defect in DNA
      replication. Levels of the RAD27 gene transcript are cell cycle regulated in a
      manner similar to those for several other genes whose products are known to be
      involved in DNA replication. We discuss the possible role of Rad27 protein in DNA
      repair and replication.

PMID- 7814327
TI  - Purification and characterization of a mesohalic catalase from the halophilic
      bacterium Halobacterium halobium.
AB  - When subjected to the stress of growth in a relatively low-salt environment (1.25
      M NaCl), the halophilic bacterium Halobacterium halobium induces a catalase. The
      protein has been purified to electrophoretic homogeneity and has an M(r) of
      240,000 and a subunit size of approximately 62,000. The enzyme is active over a
      broad pH range of 6.5 to 10.0, with a peak in activity at pH 7.0. It has an
      isoelectric point of 4.0. This catalse, which is not readily reduced by
      dithionite, shows a Soret peak at 406 nm. Cyanide and azide inhibit the enzyme at
      micromolar concentrations, whereas maleimide is without effect. The addition of
      20 mM 3-amino-1,2,4-triazole results in a 33% inhibition in enzymatic activity.
      The tetrameric protein binds NADP in a 1:1 ratio but does not peroxidize NADPH,
      NADH, or ascorbate. Although the enzymatic activity is maximal when assayed in a
      50 mM potassium phosphate buffer with no NaCl, prolonged incubation in a buffer
      lacking NaCl results in inactive enzyme. Moreover, purification must be performed
      in the presence of 2 M NaCl. Equally as effective in retaining enzymatic function
      are NaCl, LiCl, KCl, CsCl, and NH4Cl, whereas divalent salts such as MgCl2 and
      CaCl2 result in the immediate loss of activity. The catalase is stained by
      pararosaniline, which is indicative of a glycosidic linkage. The Km for H2O2 is
      60 mM, with inhibition observed at concentrations in excess of 90 mM. Thus, the
      mesohalic catalase purified from H. halobium seems to be similar to other
      catalases, except for the salt requirements, but differs markedly from the
      constitutive halobacterial hydroperoxidase.

PMID- 7814326
TI  - An additional GerE-controlled gene encoding an abundant spore coat protein from
      Bacillus subtilis.
AB  - We describe the identification and characterization of a gene, herein designated
      cotG, encoding an abundant coat protein from the spores of Bacillus subtilis. The
      cotG open reading frame is 195 codons in length and is capable of encoding a
      polypeptide of 24 kDa that contains nine tandem copies of the 13-amino-acid long,
      approximately repeated sequence H/Y-K-K-S-Y-R/C-S/T-H/Y-K-K-S-R-S. cotG is
      located at 300 degrees on the genetic map close to another coat protein gene,
      cotB. The cotG and cotB genes are in divergent orientation and are separated by
      1.3 kb. Like the promoter for cotB, the cotG promoter is induced at a late stage
      of sporulation under the control of the RNA polymerase sigma factor sigma K and
      the DNA-binding protein GerE. The -10 and -35 nucleotide sequences of the cotG
      promoter resemble those of other promoters recognized by sigma K-containing RNA
      polymerase, and centered 70 bp upstream of the apparent start site is a sequence
      that matches the consensus binding site for GerE. Spore coat proteins from a
      newly constructed cotG null mutant lack not only CotG but also CotB, a finding
      that suggests that CotG may be a morphogenetic protein that is required for the
      incorporation of CotB into the coat.

PMID- 7814328
TI  - Dual mode of energy coupling by the oxyanion-translocating ArsB protein.
AB  - The arsA and arsB genes of the ars operon of R-factor R773 confer arsenite
      resistance in Escherichia coli by coding for an anion-translocating ATPase.
      Arsenite resistance and the in vivo energetics of arsenite transport were
      compared in cells expressing the arsA and arsB genes and those expressing just
      the arsB gene. Cells expressing the arsB gene exhibited intermediate arsenite
      resistance compared with cells expressing both the arsA and arsB genes. Both
      types of cells exhibited energy-dependent arsenite exclusion. Exclusion of 73AsO2
      from cells expressing only the arsB gene was coupled to electrochemical energy,
      while in cells expressing both genes, transport was coupled to chemical energy,
      most likely ATP. These results suggest that the Ars anion transport system can be
      either an obligatory ATP-coupled primary pump or a secondary carrier coupled to
      the proton motive force, depending on the subunit composition of the transport
      complex.

PMID- 7814329
TI  - Isolation and characterization of adenylate kinase (adk) mutations in Salmonella
      typhimurium which block the ability of glycine betaine to function as an
      osmoprotectant.
AB  - Mutants of Salmonella typhimurium that were not protected by glycine betaine (GB)
      but could still use proline as an osmoprotectant in media of high osmolality were
      isolated. The mutations responsible for this phenotype proved to be alleles of
      the adenylate kinase (adk) gene, as shown by genetic mapping, sequencing of the
      cloned mutant alleles, complementation with the Escherichia coli adk gene, and
      assay of Adk enzyme activity in crude extracts. One of the mutations was in the
      untranslated leader of the adk mRNA, a second was in the putative Shine-Dalgarno
      sequence, and a third was in the coding region of the gene. The loss of
      osmoprotection by GB was shown to be due to the fact that the accumulation of
      this solute actually resulted in a severe inhibition of growth in the adk
      mutants. The addition of GB in the presence of 0.5 M NaCl resulted in a rapid
      decline in the ATP pool and a dramatic increase in the AMP pool in the mutants.
      Proline, which is not toxic to the adk mutants, did not have any significant
      effects on the cellular levels of ATP and AMP. The mutants exhibited two
      different phenotypes with respect to the utilization of other osmoprotectants:
      they were also inhibited by propiothiobetaine, L-carnitine, and gamma
      butyrobetaine, but they were stimulated normally in media of high osmolality by
      proline, choline-O-sulfate, and stachydrine.

PMID- 7814330
TI  - Discontinuities in the evolution of Pseudomonas putida cat genes.
AB  - The organization and transcriptional control of chromosomal cat genes (required
      for dissimilation of catechol by the beta-ketoadipate pathway) in the Pseudomonas
      putida biotype strain (ATCC 12633) are reported. Nucleotide sequence reveals that
      catR is separated by 135 bp from the divergently transcribed catBC,A; catC begins
      21 nucleotides downstream from catB, and catA begins 41 nucleotides downstream
      from catC. This contrasts with the gene arrangement in other bacteria, in which
      catA lies several kilobases upstream from catB. Properties of Tn5 mutants
      confirmed earlier suggestions that catR is a transcriptional activator and
      indicated that catA is activated by CatR independently of its activation of
      catBC. CatR binds to both a DNA fragment containing the catR-catB intergenic
      region and another DNA fragment containing catC. Pseudomonas strain RB1 resembles
      P. putida in some respects. Divergence of the two Pseudomonas chromosomes was
      revealed as nucleotide substitution of about 10% after alignment of known
      portions of catR,BC,A. Divergent transcriptional controls are suggested by a
      cluster of nucleotide sequence modifications in Pseudomonas strain RB1 which
      disrupt a stem-loop structure directly upstream of catB in the P. putida
      chromosome. Abrupt divergence of the catR,BC,A nucleotide sequences was achieved
      during evolution by insertion of an 85-bp palindromic genetic element uniquely
      positioned downstream from P. putida catR and counterpoised by insertion of a
      similar palindromic sequence in the Pseudomonas strain RB1 catB-catC intergenic
      region. Properties of the palindromic genetic element suggest that it may serve
      functions analogous to those of repetitive extragenic palindromic sequences and
      enteric repetitive intergenic consensus sequences in enteric bacteria.

PMID- 7814331
TI  - UDP-glucose is a potential intracellular signal molecule in the control of
      expression of sigma S and sigma S-dependent genes in Escherichia coli.
AB  - The sigma S subunit of RNA polymerase is the master regulator of a regulatory
      network that controls stationary-phase induction as well as osmotic regulation of
      many genes in Escherichia coli. In an attempt to identify additional regulatory
      components in this network, we have isolated Tn10 insertion mutations that in
      trans alter the expression of osmY and other sigma S-dependent genes. One of
      these mutations conferred glucose sensitivity and was localized in pgi (encoding
      phosphoglucose isomerase). pgi::Tn10 strains exhibit increased basal levels of
      expression of osmY and otsBA in exponentially growing cells and reduced osmotic
      inducibility of these genes. A similar phenotype was also observed for pgm and
      galU mutants, which are deficient in phosphoglucomutase and UDP-glucose
      pyrophosphorylase, respectively. This indicates that the observed effects on gene
      expression are related to the lack of UDP-glucose (or a derivative thereof),
      which is common to all three mutants. Mutants deficient in UDP-galactose
      epimerase (galE mutants) and trehalose-6-phosphate synthase (otsA mutants) do not
      exhibit such an effect on gene expression, and an mdoA mutant that is deficient
      in the first step of the synthesis of membrane-derived oligosaccharides, shows
      only a partial increase in the expression of osmY. We therefore propose that the
      cellular content of UDP-glucose serves as an internal signal that controls
      expression of osmY and other sigma S-dependent genes. In addition, we demonstrate
      that pgi, pgm, and galU mutants contain increased levels of sigma S during steady
      state growth, indicating that UDP-glucose interferes with the expression of sigma
      S itself.

PMID- 7814332
TI  - Genetic and physical mapping of genes involved in pyoverdin production in
      Pseudomonas aeruginosa PAO.
AB  - Pseudomonas aeruginosa PAO was mutagenized with Tn1737KH, a type I transcription
      probe transposon containing a promoterless lacZ (beta-galactosidase) gene, and 24
      insertion mutants that did not grow under iron-deficient conditions were
      isolated. None of the culture supernatants from any mutants contained pyoverdin,
      a low-molecular-weight siderophore able to sequester ferric iron at very high
      affinity, and the growth defects of the mutants were all phenotypically recovered
      by the addition of the culture supernatant from the wild-type strain. These
      phenotypes led to the inference that all the mutants had defects in the genes
      (pvd genes) for production of pyoverdin. In some pvd::Tn1737KH mutants, high
      levels of beta-galactosidase activities were observed, and such activities were
      drastically reduced by the addition of ferric ion in the culture media,
      indicating that the expression of at least some pvd genes is regulated at the
      transcriptional level. Molecular cloning and physical analysis of the chromosomal
      fragments with Tn1737KH insertions allowed us to allocate all the mutations
      within a 103-kb region, referred to as the pvd region, that was found to locate
      at 47 min on the genetic map of PAO. Further physical mapping and Southern
      analysis showed that there is a 10-kb overlap between the pvd region and the 125
      kb catA region described by Zhang and Holloway (C. Zhang and B. W. Holloway, J.
      Gen. Microbiol. 138:1097-1107, 1992). We could hence illustrate the physical map
      of the P. aeruginosa chromosome with a size of 218 kb.

PMID- 7814333
TI  - Isolation and characterization of mutants defective in the cyanide-insensitive
      respiratory pathway of Pseudomonas aeruginosa.
AB  - The branched respiratory chain of Pseudomonas aeruginosa contains at least two
      terminal oxidases which are active under normal physiological conditions. One of
      these, cytochrome co, is a cytochrome c oxidase which is completely inhibited by
      concentrations of the respiratory inhibitor potassium cyanide as low as 100
      microM. The second oxidase, the cyanide-insensitive oxidase, is resistant to
      cyanide concentrations in excess of 1 mM as well as to sodium azide. In this
      work, we describe the isolation and characterization of a mutant of P. aeruginosa
      defective in cyanide-insensitive respiration. This insertion mutant was isolated
      with mini-D171 (a replication-defective derivative of the P. aeruginosa phage
      D3112) as a mutagen and by screening the resulting tetracycline-resistant
      transductants for the loss of ability to grow in the presence of 1 mM sodium
      azide. Polarographic studies on the NADH-mediated respiration rate of the mutant
      indicated an approximate 50% loss of activity, and titration of this activity
      against increasing cyanide concentrations gave a monophasic curve clearly showing
      the complete loss of cyanide-insensitive respiration. The mutated gene for a
      mutant affected in the cyanide-insensitive, oxidase-terminated respiratory
      pathway has been designated cio. We have complemented the azide-sensitive
      phenotype of this mutant with a wild-type copy of the gene by in vivo cloning
      with another mini-D element, mini-D386, carried on plasmid pADD386. The
      complemented cio mutant regained the ability to grow on medium containing 1 mM
      azide, titration of its NADH oxidase activity with cyanide gave a biphasic curve
      similar to that of the wild-type organism, and the respiration rate returned to
      normal levels. Spectral analysis of the cytochrome contents of the membranes of
      the wild type, the cio mutant, and the complemented mutant suggests that the cio
      mutant is not defective in any membrane-bound cytochromes and that the
      complementing gene does not encode a heme protein.

PMID- 7814334
TI  - Physical map of the Clostridium beijerinckii (formerly Clostridium
      acetobutylicum) NCIMB 8052 chromosome.
AB  - A combined physical and genetic map of the single, circular, 6.7-Mbp chromosome
      of the NCIMB 8052 strain of Clostridium beijerinckii (formerly Clostridium
      acetobutylicum) has been constructed by using a combination of cloned DNA
      fragments as hybridization probes and a bank of strains harboring insertions of
      the conjugative transposon Tn1545. The positions of 81 restriction endonuclease
      cleavage sites and 32 genes have been determined. Eight genes concerned with
      solventogenic fermentation are found at three different locations. The chromosome
      contains at least 13 rrn operons, 11 of which have been located on the map. Their
      transcriptional orientation diverges from the presumed location of the
      replication origin.

PMID- 7814335
TI  - A new regulatory element modulates homoserine lactone-mediated autoinduction of
      Ti plasmid conjugal transfer.
AB  - Conjugal transfer of the Agrobacterium tumefaciens nopaline-type Ti plasmid
      pTiC58 is induced by agrocinopines A and B, opines secreted by crown gall tumors
      induced by the bacterium. This regulation functions through the transcriptional
      repressor, AccR. However, actual transcription of the tra genes is regulated by
      autoinduction through the activator TraR and the substituted homoserine lactone
      second messenger, Agrobacterium autoinducer (AAI). We have identified a new
      regulatory element that modulates the response of TraR to AAI. The gene, called
      traM, suppresses TraR-AAI activation of transcription of tra genes carried on
      recombinant clones. The suppression could be relieved by increasing the
      expression of TraR but not by increasing AAI levels. traM is located between traR
      and traAF on pTiC58 and is transcribed in the clockwise direction. The 306-bp
      gene encodes an 11.2-kDa protein showing no significant relatedness to other
      proteins in the databases. Mutations in traM in pTiC58 conferred a transfer
      constitutive phenotype, and strains harboring the Ti plasmid produced easily
      detectable amounts of AAI. These same mutations engineered into the transfer
      constitutive Ti plasmid pTiC58 delta accR conferred a hyperconjugal phenotype and
      very high levels of AAI production. Expression of traM required TraR, indicating
      that transcription of the gene is regulated by the autoinduction system. TraM had
      no effect on the expression of traR, demonstrating that the suppressive effect is
      not due to repression of the gene encoding the activator. These results suggest
      that TraM is not a direct transcriptional regulator. Since the suppressive effect
      is demonstrable only when traM is overexpressed with respect to traR, we suggest
      that TraM functions to sequester TraR from the very small amounts of AAI produced
      under conditions when the agrocinopines are not present.

PMID- 7814336
TI  - D-serine deaminase is a stringent selective marker in genetic crosses.
AB  - The presence of the locus for D-serine deaminase (dsd) renders bacteria resistant
      to growth inhibition by D-serine and enables them to grow with D-serine as the
      sole nitrogen source. The two properties permit stringent selection in genetic
      crosses and make the D-serine deaminase gene an excellent marker, especially in
      the construction of strains for which the use of antibiotic resistance genes as
      selective markers is not allowed.

PMID- 7814337
TI  - A mutation in either dsbA or dsbB, a gene encoding a component of a periplasmic
      disulfide bond-catalyzing system, is required for high-level expression of the
      Bacteroides fragilis metallo-beta-lactamase, CcrA, in Escherichia coli.
AB  - The metallo-beta-lactamase gene, ccrA, from Bacteroides fragilis is functionally
      expressed in Escherichia coli only in the presence of a genomic mutation in iarA
      or iarB (increased ampicillin resistance), identified in this study as dsbA or
      dsbB, respectively. DsbA and DsbB are components of a periplasmic protein
      disulfide bond-catalyzing system. Data indicated that DsbA interacted with CcrA,
      creating aberrant disulfide bond linkages that render CcrA proteolytically
      unstable. Mutations in dsbA or dsbB permissive for CcrA expression eliminated or
      greatly reduced DsbA activity, allowing CcrA to assume a disulfide bond-free and
      proteolytically stable conformation.

PMID- 7814338
TI  - Molecular cloning, DNA sequence analysis, and characterization of the
      Corynebacterium diphtheriae dtxR homolog from Brevibacterium lactofermentum.
AB  - A homolog of the Corynebacterium diphtheriae dtxR gene was isolated from
      Brevibacterium lactofermentum. The product of the B. lactofermentum dtxR gene was
      immunoreactive with polyclonal anti-DtxR antibodies and functioned as an iron
      activated repressor capable of regulating the expression of beta-galactosidase
      from a diphtheria tox promoter/operator transcriptional fusion in recombinant
      Escherichia coli. The extents of induction by increasing concentrations of the
      chelator 2,2'-dipyridyl were identical in cells expressing DtxR from either C.
      diphtheriae or B. lactofermentum.

PMID- 7814339
TI  - Phylogeny of Sym plasmids of rhizobia by PCR-based sequencing of a nodC segment.
AB  - To understand the host specificity of rhizobia and the relationship between the
      evolution of Sym plasmids and that of host plants, we determined partial nodC
      sequences of 10 representative rhizobium strains and then constructed an
      evolutionary tree for the deduced amino acid sequences with four published
      sequences. These coding sequences yield a phylogenetic tree similar to that for
      leghemoglobin of host plants, suggesting that the evolution of common nodulation
      genes may be linked to host legume evolution and speciation.

PMID- 7814340
TI  - Mapping of genes involved in macromolecular synthesis on the chromosome of
      Streptomyces coelicolor A3(2).
AB  - The genes for the beta, beta', and seven sigma factor subunits of RNA polymerase,
      for elongation factors EF-Tu1 and EF-Tu3, and for six rRNA operons were mapped on
      the combined genetic and physical map of the Streptomyces coelicolor chromosome.
      Like the previously mapped tRNA genes, the RNA polymerase and rRNA genes map to
      scattered positions. The lack of rRNA operons in the immediate vicinity of the
      origin of replication (oriC) and the absence of tRNA genes in any of the rRNA
      operons are novel features of the Streptomyces chromosome.

PMID- 7814341
TI  - Functional analysis of putative beta-ketoacyl:acyl carrier protein synthase and
      acyltransferase active site motifs in a type II polyketide synthase of
      Streptomyces glaucescens.
AB  - The significance of potential active site motifs for acyltransferase and beta
      ketoacyl:acyl carrier protein synthase regions within the TcmK protein was
      investigated by determining the effects of mutations in the proposed active sites
      on the production of tetracenomycins F2 and C. In a Streptomyces glaucescens
      tcmGHI JKLMNO null mutant, plasmids carrying the S351A mutation produced high
      amounts of tetracenomycin F2 but plasmids carrying the C173A or C173S mutation or
      the H350L-S351A double mutation produced no detectable amount of any known
      intermediate. In a tcmK mutant, plasmids with the S351A mutation restored high
      production of tetracenomycin C and plasmids carrying the other mutations were
      able to complement the chromosomal defect to some extent. None of the mutations
      affected the amount of TcmK produced.

PMID- 7814342
TI  - Purification and characterization of a maltase from the extremely thermophilic
      crenarchaeote Sulfolobus solfataricus.
AB  - A soluble maltase (alpha-glucosidase) with an apparent subunit mass of 80 kDa was
      purified to homogeneity from Sulfolobus solfataricus. The enzyme liberates
      glucose from maltose and malto-oligomers. Maximal activity was observed at 105
      degrees C, with half-lives of 11 h (85 degrees C), 3.0 h (95 degrees C), and 2.75
      h (100 degrees C). The enzyme was generally resistant to proteolysis and
      denaturants including aliphatic alcohols. n-Propanol treatment at 85 degrees C
      increased both Km and Vmax for maltose hydrolysis.

PMID- 7814343
TI  - Genetic competence in Escherichia coli requires poly-beta-hydroxybutyrate/calcium
      polyphosphate membrane complexes and certain divalent cations.
AB  - In earlier studies of genetic competence in Escherichia coli induced with calcium
      containing buffers, a strong correlation was found between transformation
      efficiency and the formation of poly-beta-hydroxybutyrate/calcium polyphosphate
      (PHB/Ca2+/PPi) complexes in the plasma membranes. In this study, we replaced Ca2+
      with one of a number of other cations--monovalent, divalent, and trivalent--and
      found significant numbers of transformants (transformation efficiency, >
      10(5)/micrograms of pBR322 DNA) only when the cells had high levels of
      PHB/Ca2+/PPi and the medium contained at least one of the divalent cations Ca2+,
      Mn2+, Sr2+, or Mg2+. Cells with high levels of the complexes were not competent
      when the medium did not contain these cations, but the cations were also
      ineffectual when the cells had few complexes. Surprisingly, Mn, Sr, and Mg were
      not incorporated into the complexes in place of Ca. These results indicate that
      PHB/Ca2+/PPi complexes and the above-mentioned divalent cations each have
      essential but disparate roles in genetic competence. Moreover, the strong
      selectivity of PHB/PPi for Ca2+ suggests the binding sites in the complexes are
      ionophoretic.

PMID- 7814344
TI  - Fluoxetine in posttraumatic stress disorder.
AB  - BACKGROUND: This study was designed to establish the efficacy of the serotonin
      reuptake blocker fluoxetine in the treatment of posttraumatic stress disorder
      (PTSD). METHOD: 64 subjects (22 women and 42 men; 31 veterans and 33 nonveterans)
      with PTSD entered a 5-week randomized double-blind trial comparing fluoxetine (N
      = 33) and placebo (N = 31). RESULTS: By Week 5 fluoxetine, but not placebo,
      significantly reduced overall PTSD symptomatology, as assessed by the Clinician
      Administered PTSD Scale (CAPS) score. Changes were most marked in the arousal and
      numbing symptom subcategories. Non-VA patients responded much better than VA
      patients. Fluoxetine was an effective antidepressant independent of its effects
      on PTSD. CONCLUSION: Fluoxetine is an effective pharmacotherapeutic agent for
      treating PTSD and its associated features, particularly in patients without
      chronic treatment histories.

PMID- 7814345
TI  - Suicide in major depression in different treatment settings.
AB  - BACKGROUND: Whether suicide victims having suffered from major depression differ
      in their characteristics and treatment of depression received in various settings
      prior to death has been unknown. METHOD: From a random sample representing all
      completed suicides in Finland within a 12-month period, cases with a best
      estimate diagnosis of current unipolar DSM-III-R major depression (N = 71) were
      comprehensively analyzed using the method of psychological autopsy. Suicide
      victims with major depression were classified according to treatment setting, and
      the victims in different settings--psychiatric care (N = 32), medical care (N =
      27), and no contact with health care (N = 12)--were compared. RESULTS: The sex
      distribution of suicides who had major depression was equal within psychiatric
      care; but in medical care or without contact with health care, 77% (30 of 39)
      were men (p = .018). Significantly more victims in psychiatric than in medical
      care had communicated to attending personnel their intent to commit suicide (59%
      [19 of 32] vs. 19% [5 of 27], p = .004). Antidepressants were received by 60% of
      victims in psychiatric care but only 16% in medical care (p = .002). CONCLUSION:
      Suicide victims with major depression differ in sex distribution and
      communication of suicide intent among treatment settings, which may complicate
      the ability to generalize research findings, particularly from psychiatric to
      medical care. Promoting suicide prevention in major depressive disorders would
      seem to require improving not only the quality of treatment within psychiatric
      care, but also basic skills in recognizing and treating depression in medical
      care, especially for male patients.

PMID- 7814346
TI  - Diagnostic reassessment and treatment response in schizophrenia.
AB  - BACKGROUND: The reasons for poor treatment response in some patients with
      schizophrenia remain unclear. It is possible that misdiagnosis of
      nonschizophrenic disorders as schizophrenia could result in suboptimal
      pharmacotherapy in some patients. METHOD: To assess this possibility, 110
      severely ill, chronic patients with a referral diagnosis of schizophrenia were
      comprehensively assessed and rediagnosed according to DSM-III-R criteria. Global
      Assessment of Function (GAF) and Clinical Global Impressions (CGI) ratings were
      made at admission and at discharge from the ward, after the implementation of
      individualized treatment plans. RESULTS: The diagnosis of schizophrenia was
      confirmed in 80 patients (73%) and revised to another type of psychotic illness
      in 30 patients (27%). The GAF and CGI ratings were similar at admission in
      patients with confirmed and revised diagnoses. All patients improved by the time
      of discharge (p = .0001); however, patients with a revised diagnosis improved
      more than those with confirmed schizophrenia (p = .02). Patients with a revised
      diagnosis were less likely to require continued hospitalization on chronic care
      wards (p = .004). At admission, medication regimens were similar in the two
      groups of patients. At discharge, patients with a revised diagnosis were less
      likely to have received neuroleptics (p = .007) and more likely to have received
      antimanic drugs (p = .0002) or electroconvulsive therapy (p = .0004). CONCLUSION:
      These findings from a clinical sample suggest that diagnostic reassessment is an
      important first step in the management of apparently refractory schizophrenia.

PMID- 7814347
TI  - Is there a role for neuroleptics in bipolar depression?
AB  - BACKGROUND: Lithium, carbamazepine, and valproic acid reduce relapse rates in
      most bipolar patients. However, some patients with bipolar illness fail to obtain
      antidepressant benefits from these medications, despite appropriate dosages of
      and duration on therapy with these drugs. METHOD: Three bipolar patients were
      followed in an open fashion on thymoleptic and neuroleptic medications. With
      discontinuation of neuroleptics, each patient relapsed into depression and was
      then restarted on neuroleptic treatment. RESULTS: These three patients responded
      rapidly to readministration of neuroleptics to their pharmacologic regimen.
      CONCLUSION: Some bipolar patients experience depressive relapse following
      neuroleptic discontinuation. With reinstitution of the neuroleptic, they show
      rapid improvement in mood.

PMID- 7814348
TI  - Behavioral effects of trazodone in Alzheimer's disease.
AB  - BACKGROUND: Central serotonin depletion may contribute to the anxiety,
      restlessness, irritability, and affective disturbance seen in a variety of
      psychiatric conditions, particularly dementia of the Alzheimer's type (DAT) in
      which brain concentrations of both 5-hydroxytryptamine (5-HT) and its 5
      hydroxyindoleacetic acid (5-HIAA) metabolite are reduced. METHOD: Trazodone, a
      serotonergic antidepressant with alpha 2-adrenergic blocking activity, was
      administered to 13 patients with DAT in an open 10-week pilot study at a dose of
      25 mg t.i.d. Behavioral and affective disturbance was assessed pretreatment and
      posttreatment using semistructured interview and Jouvent's Depressed Mood and
      Gottfries-Brane-Steen scales. RESULTS: Irritability, anxiety, restlessness, and
      affective disturbance were all decreased (p < .05). No side effects were
      observed. Mean Mini Mental State scores were unaffected by treatment. CONCLUSION:
      The hypothesis that trazodone corrects behavioral and affective disturbance
      induced by serotonin depletion in DAT requires confirmation in a double-blind
      placebo-controlled trial.

PMID- 7814349
TI  - Panic disorder in pregnancy.
AB  - BACKGROUND: Some reports have suggested that panic disorder may go into remission
      during pregnancy. The universality of this finding, however, is questionable. In
      this retrospective survey, we examined the influence of pregnancy on the course
      of panic disorder in 46 women who developed panic disorder either before, during,
      or between pregnancies. METHOD: A questionnaire inquired about the clinical
      course of panic disorder before, during, and after each pregnancy. Additional
      questions were asked about symptom change following breastfeeding and about
      caffeine use during pregnancy. The questionnaire was mailed to 138 women with a
      DSM-III-R diagnosis of panic disorder who had been assessed in our Anxiety
      Disorders Clinic. RESULTS: Response rate to the questionnaire was 70%. Forty-six
      women reported a total of 67 pregnancies occurring after the development of panic
      disorder. Of these pregnancies, 43% were associated with improvement in panic
      symptoms, 33% with worsening, and 23% with no change. Furthermore, women were
      unlikely to experience the same outcome (i.e., worsening, improvement, or no
      change) in subsequent pregnancies. In contrast, the majority (63%) of pregnancies
      were associated with exacerbation of symptoms in the postpartum period. No
      association with weaning or caffeine use was detected. CONCLUSION: Our findings
      suggest that pregnancy may have a highly variable influence on the course of
      panic disorder. In contrast, postpartum worsening of panic may be a more
      consistent phenomenon. Implications for pregnancy counseling and management are
      discussed.

PMID- 7814350
TI  - Enhancing compliance in schizophrenic patients by weekly dosing with
      levothyroxine sodium.

PMID- 7814351
TI  - Sertraline as the cause of inappropriate antidiuretic hormone secretion.

PMID- 7814352
TI  - Guy de Maupassant's "The Horla" and sleep paralysis.

PMID- 7814353
TI  - SSRI withdrawal buzz.

PMID- 7814354
TI  - Do compulsive buyers and kleptomaniacs share identical characteristics?

PMID- 7814355
TI  - Recognition and treatment of depression in a primary care setting.
AB  - Depression is a highly treatable disease that is more prevalent among primary
      care patients than hypertension. Primary care physicians must become accustomed
      to screening for and treating depression just as they screen for and treat
      hypertension. A psychiatrist should be consulted for severe cases of depression.
      The introduction of the serotonin selective reuptake inhibitors (SSRIs),
      antidepressants that are far less toxic and have a milder side effect profile
      than the tricyclic antidepressants (TCAs), has made it possible for depression to
      be treated more successfully in the primary care setting. Unlike the TCAs, the
      SSRIs have not been lethal in overdose. Early diagnosis and early treatment can
      reduce the morbidity and mortality associated with depression and can also reduce
      the costs associated with misdiagnosis. This article reviews the difficulties
      inherent in diagnosing depression in this health care setting, including
      somatization and the coexistence of other medical disorders. Suggestions are
      offered for effective screening and diagnosis, and a practical approach is given
      for explaining the diagnosis, which may help moderate patient denial or fear of
      stigma. Current pharmacotherapeutic options for treating mild-to-moderate
      depression are also summarized.

PMID- 7814357
TI  - Pharmacogenetics and drug metabolism of newer antidepressant agents.
AB  - A wide variety of drugs are metabolized by the human cytochrome P450 system,
      including antidepressants such as tricyclic antidepressants and serotonin
      selective reuptake inhibitors (SSRIs). Each P450 isoenzyme is the product of a
      separate gene; a number of genes have multiple alleles that result in genetic
      polymorphism in the population. Both CYP2D6 and CYP2C gene families are
      polymorphic; both families are important in antidepressant metabolism. A number
      of polymorphisms result in dysfunctional or inactive enzymes. The clinical
      importance is highly dependent upon the patient's clinical state, coadministered
      drugs, therapeutic index, and the relative importance of the defective pathway in
      the total process of drug elimination. In addition, a number of drugs can also
      act as P450 enzyme inhibitors, which have the potential of causing drug
      interactions. In patient management, it is important to consider the fact that
      most antidepressants can also act as enzyme inhibitors. A number of adverse
      reactions resulting from coadministration of tricyclic antidepressants and SSRIs
      have been described. Such drug interactions can be minimized or avoided by
      following simple clinical logic.

PMID- 7814356
TI  - Evolutionary trends in the pharmacotherapeutic management of depression.
AB  - The past decade has brought an exponential increase in our knowledge of the
      pharmacotherapeutic management of depression. Much has been learned about the
      prevalence, risks, and course of depression in the general population, the
      elderly, and patients with comorbid medical illnesses and about the biological
      basis of depression. This article reviews evolving trends in the diagnosis and
      management of depression and evaluates the main classes of antidepressants.
      Although depression carries a high risk of morbidity and mortality, it is very
      treatable, and early diagnosis and early treatment are now emphasized.
      Antidepressant medication is continued after the patients' acute depressive
      symptoms resolve, sometimes for as long as 1 to 5 years to prevent relapse and
      recurrence of depression; in addition, full doses, rather than lower doses of
      antidepressant are prescribed for maintenance therapy. The armamentarium of
      antidepressants too has changed. In addition to monoamine oxidase inhibitors and
      tricyclic and tetracyclic antidepressants, the serotonin reuptake inhibitors
      fluoxetine, sertraline, and paroxetine are now available, as well as a group of
      antidepressants with atypical mechanisms of action that includes bupropion,
      trazodone, venlafaxin, and nefazodone. Although comparable in efficacy to the
      tricyclic antidepressants, these new drugs are safer and better tolerated because
      they are believed to act selectively on specific neurotransmitter systems.

PMID- 7814358
TI  - Therapeutic considerations in treating depression in the elderly.
AB  - The elderly depressed patient has a clinical picture unlike that of the younger
      individual. The pharmacokinetic profile, for example, changes in the normal aging
      process, which must be considered in choosing the proper antidepressant--and
      dosage--for an older person. Depressive illnesses are described in this review,
      with the focus on symptoms, prevalence, diagnosis, and treatment modalities.
      Cited are results of studies comparing tricyclic antidepressants and selective
      serotonin reuptake inhibitors (SSRIs). Equivalent efficacy of the two classes of
      drugs was not unexpected. The higher degree of tolerability with SSRIs, however,
      should be of special interest to the clinician treating the elderly.

PMID- 7814360
TI  - Mammalian membrane-bound adenylyl cyclases.

PMID- 7814359
TI  - Guidelines for the long-term treatment of depression.
AB  - Depression is frequently a recurrent and sometimes a chronic illness.
      Unfortunately, most research on treatment has focused almost exclusively on the
      short-term. For example, the majority of clinical trials of medications and
      psychotherapeutic approaches last only 6 to 16 weeks. Relatively little research
      has been conducted on continuation treatment (usually 3-6 months) to prevent
      relapses and on maintenance treatment (6-24 months) to prevent recurrences. This
      paper will review continuation and maintenance phase pharmacotherapeutic trials
      and will make recommendations for clinical treatment of patients during these
      periods.

PMID- 7814361
TI  - Isoforms of yeast cytochrome c oxidase subunit V affect the binuclear reaction
      center and alter the kinetics of interaction with the isoforms of yeast
      cytochrome c.
AB  - Subunit V, one of the nuclear-coded subunits of yeast cytochrome c oxidase, has
      two isoforms, Va and Vb. These alter the in vivo intramolecular rates of electron
      transfer within the holoenzyme (Waterland, R. A., Basu, A., Chance, B., and
      Poyton, R. O. (1991) J. Biol. Chem. 266, 4180-4186). The isozyme with Vb has a
      higher turnover rate and a higher intramolecular transfer rate than the isozyme
      with Va. To determine how these isoforms affect catalysis, we have examined their
      effects on the binuclear reaction center and on the interaction between
      cytochrome c oxidase and the two isoforms, iso-1 and iso-2, of yeast cytochrome
      c. Infrared spectroscopy of carbon monoxide liganded to heme a3 has revealed a
      single conformer for the binuclear reaction center in the isozyme with Vb but two
      discrete conformers in the isozyme with Va. The kinetics of interaction for all
      four pairwise combinations of isozymes with each subunit V isoform and the two
      cytochrome c isoforms are biphasic, with high and low affinity electron transfer
      reactions. In general, the isoforms of cytochrome c and subunit V do not alter
      the Km but do affect the TNmax. The TNmax for isozymes carrying Vb are higher at
      both high and low affinity sites for each cytochrome c isoform. Iso-1-cytochrome
      c supports a higher TNmax than Iso-2-cytochrome c. Surprisingly, the
      combinatorial effect of both sets of isoforms on TNmax is minimized with the
      pairs of isoforms (iso-1-cytochrome c and subunit Va or iso-2 and subunit Vb)
      that are co-expressed in cells. Together, these findings support the conclusion
      that the subunit V isoforms modulate catalysis and suggest that they do so by
      affecting the environment or structure of the binuclear reaction center. They
      also suggest that the coexpression of the two cytochrome c isoforms with two
      subunit V isoforms serves to minimize differences in electron transfer rates
      brought about by the subunit V isoforms.

PMID- 7814362
TI  - Requirement for the expression of poly(ADP-ribose) polymerase during the early
      stages of differentiation of 3T3-L1 preadipocytes, as studied by antisense RNA
      induction.
AB  - Poly(ADP-ribose) polymerase (PADPRP) is biologically significant in the rejoining
      of DNA strand breaks. Post confluent cultures of 3T3-L1 preadipocytes showed
      marked increases in PADPRP protein and activity when the cells were induced to
      differentiate into adipocytes. When this increase in PADPRP expression was
      prevented in stably transfected 3T3-L1 cells by induction of PADPRP antisense RNA
      synthesis, the cells did not differentiate nor undergo the two or three rounds of
      DNA replication that are required for initiation of the differentiation process.
      3T3-L1 cells expressing PADPRP antisense RNA under differentiation conditions
      were easily detached from plates and in some cases eventually died. When newly
      expressed PADPRP protein and DNA synthesis was assessed in cells at zero time or
      at 24 h after induction of differentiation by incorporation of bromodeoxyuridine
      or [3H]thymidine into DNA, significant incorporation was shown to occur in
      control cells after 24 h, but not in antisense cells. Furthermore, during the
      first 24 h, the co-immunoprecipitation of PADPRP and DNA polymerase alpha was
      observed in control cells, whereas no such complex formation was noted in the
      induced antisense cells, nor in uninduced control cells.

PMID- 7814363
TI  - Evidence for Cu(II) reduction as a component of copper uptake by Saccharomyces
      cerevisiae.
AB  - The yeast Saccharomyces cerevisiae contains a plasma membrane reductase activity
      associated with the gene product of the FRE1 locus. This reductase is required
      for Fe(III) uptake by this yeast; transcription from FRE1 is repressed by iron
      (Dancis, A., Klausner, R. D., Hinnebusch, A. G., and Barriocanal, J. G. (1990)
      Mol. Cell. Biol. 10, 2294-2301). We show here that Cu(II) is equally efficient at
      repressing FRE1 transcription and is an excellent substrate for the Fre1p
      reductase. This reductase activity is required for 50-70% of the uptake of 64Cu
      by wild type cells. Under conditions of low Fre1-dependent activity, cells retain
      30-70% of Cu(II) reductase activity but only 8-25% of Fe(III) reductase activity.
      While Fre1p-dependent activity is 100% inhibitable by Pt(II), this residual
      Cu(II) reduction is insensitive to this inhibitor. The data suggest the presence
      of a Fre1p-independent reductase activity in the yeast plasma membrane which is
      relatively specific for Cu(II) and which supports copper uptake in the absence of
      FRE1 expression. The gene product of MAC1, which is required for regulation of
      FRE1 transcription, is also required for expression of Cu(II) reduction activity.
      This is due in part to its role in the regulation of FRE1; however, it is
      required for expression of the putative Cu(II) reductase, as well. Similarly, a
      gain-of-function mutation, MAC1up1, which causes elevated and unregulated
      transcription from FRE1 and elevated Fe(III) reduction and 59Fe uptake exhibits a
      similar phenotype with respect to Cu(II) reduction and 64Cu uptake. Ascorbate,
      which reduces periplasmic Cu(II) to Cu(I), suppresses the dependence of 64Cu
      uptake on plasma membrane reductase activity as is the case for ascorbate
      supported 59Fe uptake. The close parallels between Cu(II) and Fe(III) reduction,
      and 64Cu and 59Fe uptake, strongly suggest that Cu(II) uptake by yeast involves a
      Cu(I) intermediate. This results in the reductive mobilization of the copper from
      periplasmic chelating agents, making the free ion available for translocation
      across the plasma membrane.

PMID- 7814364
TI  - A heterotrimeric Gi3-protein controls autophagic sequestration in the human colon
      cancer cell line HT-29.
AB  - Human colon cancer HT-29 cells exhibit a differentiation-dependent autophagic
      lysosomal pathway that is responsible for the degradation of a pool of newly
      synthesized N-linked glycoproteins in undifferentiated cells. In the present
      study, we have investigated the molecular control of this degradative pathway in
      undifferentiated HT-29 cells. For this purpose, we have modulated the function
      and expression of the heterotrimeric G-proteins (Gs and Gi) in these cells. After
      pertussis toxin treatment which ADP-ribosylates heterotrimeric Gi-proteins, we
      observed an inhibition of autophagic sequestration and the complete restoration
      of the passage of N-linked glycoproteins through the Golgi complex. In contrast,
      autophagic sequestration was not reduced by cholera toxin, which acts on
      heterotrimeric Gs-proteins. Further insights on the nature of the pertussis toxin
      sensitive alpha subunit controlling autophagic sequestration were obtained by
      cDNA transfections of alpha i subunits. Overexpression of the alpha i3 subunit
      increased autophagic sequestration and degradation in undifferentiated cells,
      whereas overexpression of the alpha i2 subunit, the only other pertussis toxin
      sensitive alpha subunit expressed in HT-29 cells, did not alter the rate of
      autophagy.

PMID- 7814365
TI  - Mutational analysis of Saccharomyces cerevisiae ARF1.
AB  - Wild type and eight point mutants of Saccharomyces cerevisiae ARF1 were expressed
      in yeast and bacteria to determine the roles of specific residues in in vivo and
      in vitro activities. Mutations at either Gly2 or Asp26 resulted in recessive loss
      of function. It was concluded that N-myristoylation is required for Arf action in
      cells but not for either nucleotide exchange or cofactor activities in vitro.
      Asp26 (homologous to Gly12 of p21ras) was essential for the binding of the
      activating nucleotide, guanosine 5'-3-O-(thio)triphosphate. This is in marked
      contrast to results obtained after mutagenesis of the homologous residue in
      p21ras or Gs alpha, and suggests a fundamental difference in the guanine
      nucleotide binding site of Arf with respect to these other GTP-binding proteins.
      Two dominant alleles were also identified, one activating dominant ([Q71L]Arf1)
      and the other ([N126I]) a negative dominant. A conditional allele, [W66R]Arf1,
      was characterized and shown to have approximately 300-fold lower specific
      activity in an in vitro Arf assay. Two high-copy suppressors of this conditional
      phenotype were cloned and sequenced. One of these suppressors, SFS4, was found to
      be identical to PBS2/HOG4, recently shown to encode a microtubule-associated
      protein kinase kinase in yeast.

PMID- 7814366
TI  - The cytoplasmic tail of the G-protein-coupled receptor for parathyroid hormone
      and parathyroid hormone-related protein contains positive and negative signals
      for endocytosis.
AB  - The present studies were done to evaluate the role of the cytoplasmic tail of the
      G-protein-coupled receptor for parathyroid hormone (PTH) and PTH-related protein
      (PTHrP) in the endocytosis of agonist-occupied receptors. PTH/PTHrP receptor
      mutants progressively truncated from the C terminus were expressed in COS-7
      cells, and their ability to internalize 125I-PTHrP(1-34)amide was determined.
      Most of the C-terminal tail (91 of 127 residues) could be deleted without
      affecting internalization. However, further truncation removing residues 475-494
      resulted in a 50-60% decrease in ligand internalization. A mutant with an
      internal deletion of these 20 amino acids showed a similar reduction in
      internalization, confirming the presence of a positive endocytic signal. No
      additional positive signals were found in the membrane-proximal region of the
      tail. However, alanine mutagenesis of the membrane-proximal residues 459-461 (EVQ
      ->AAA) resulted in a mutant PTH/PTHrP receptor displaying a 40% increase in
      ligand endocytosis, indicating that EVQ functions as a negative signal. Treatment
      of COS-7 cells with hypertonic sucrose (to disrupt clathrin lattices) markedly
      suppressed (by > 80%) PTH/PTHrP receptor internalization. These results
      demonstrate the presence of both positive and negative endocytic signals in the
      membrane-proximal cytoplasmic tail of the PTH/PTHrP receptor and suggest that
      these signals regulate the ability of the receptor to accumulate in clathrin
      coated pits.

PMID- 7814367
TI  - Transcription of the rat beta 1-adrenergic receptor gene. Characterization of the
      transcript and identification of important sequences.
AB  - We have characterized the 5' and 3' ends of the rat beta 1-adrenergic receptor
      transcript using RNase protection assays and have used transient transfection
      analysis to identify regions of the beta 1-adrenergic gene 5'-flanking sequences
      which are important for expression. The transcript has multiple start sites,
      occurring primarily in two clusters at bases -250 and -280, relative to the first
      base of the initiation codon. Two potential polyadenylation signals at +2450 and
      +2732 are both functional, although the site at +2732 is preferred both in C6
      glioma cells and in heart tissue. Characterization of the gene by transient
      transfection analysis has identified a region between bases -389 and -325 which
      is necessary for expression. The specific deletion of a potentially functional
      inverted CCAAT sequence within this region does not significantly alter activity.
      In addition to the region from -389 and -325, deletion of the bases between -1
      and -159 and between -186 and -211 significantly alters expression. Both of these
      regions are down-stream from the beta 1-adrenergic receptor gene start sites and
      may function either through regulation of transcription or through alteration of
      the transcript structure.

PMID- 7814368
TI  - Expression and folding of recombinant bovine prethrombin-2 and its activation to
      thrombin.
AB  - Bovine prethrombin-2 has been produced in Escherichia coli using a T7 expression
      system. The expressed prethrombin-2 formed intracellular inclusion bodies which
      were solubilized by reversible sulfonation of the cysteines in the presence of 7
      M guanidine hydrochloride. Sulfonated prethrombin-2 was refolded in the presence
      of 4 M guanidine hydrochloride, using oxidized and reduced glutathione as the
      redox couple. The folded protein was purified by heparin affinity chromatography
      and activated to thrombin with Echis carinatus snake venom. The resulting
      thrombin was also purified by heparin affinity chromatography. Kinetic constants
      were determined for the hydrolysis of H-D-phenylalanyl-L-pipecolyl-L-arginine-p
      nitroaniline by recombinant thrombin (kcat = 123 +/- 10 s-1 and Km = 2.91 +/- 0.3
      microM). These values are in good agreement with those determined for wild-type
      thrombin (kcat = 97 +/- 8 s-1 and Km = 2.71 +- 0.25 microM). From the thrombin
      mediated release of fibrinopeptide A from fibrinogen, kcat/Km was found to be the
      same for recombinant (17.3 +/- 1.2 microM-1 s-1) and wild-type (16.7 +/- 2.0
      microM-1 s-1) thrombin. These results, taken together with circular dichroism
      spectra and the elution position of prethrombin-2 from a heparin affinity resin,
      indicate that prethrombin-2 was folded into a conformation similar to that of the
      wild-type protein. In addition, since E. coli produces deglycosylated enzymes,
      these findings suggest that the carbohydrate on the B chain of wild-type thrombin
      does not affect the amidolytic and fibrinolytic activities of thrombin. Finally,
      this expression system can be used to prepare mutants of prethrombin-2 for future
      structure-function studies involving thrombin and its substrates; some
      preliminary results of this type are presented here.

PMID- 7814369
TI  - Molecular cloning and expression of rat squalene epoxidase.
AB  - Squalene epoxidase (SE) (EC 1.14.99.7) catalyzes the first oxygenation step in
      sterol biosynthesis and is suggested to be one of the rate-limiting enzymes in
      this pathway. Rat SE cDNA was isolated by selecting yeast transformants
      expressing rat cDNA in the presence of transformants expressing rat cDNA in the
      presence of terbinafine, an inhibitor specific for fungal SE. The expression of
      rat SE in the isolated terbinafine-resistant clone was confirmed by its survival
      in the presence of either terbinafine or an inhibitor specific for mammalian SE,
      NB-598, but not in the presence of both terbinafine and NB-598. Rat SE
      polypeptide deduced from the nucleotide sequence contains 573 amino acids, and
      its molecular weight is 63,950 Da. The amino acid sequence reveals one potential
      transmembrane domain, a hydrophobic segment (Leu27 to Tyr43) in the NH2-terminal
      region. This region also contains a beta 1-alpha A-beta 2 motif, which is the
      consensus sequence for an FAD binding domain, suggesting that SE is a
      flavoenzyme. This deduced rat SE sequence is 30.2% identical to the ERG 1 gene,
      which encodes SE from an allylamine-resistant Saccharomyces cerevisiae mutant.
      Expression of a full-length rat SE protein in Escherichia coli confirms this
      polypeptide as a functional SE. This is the first report of the molecular cloning
      of mammalian SE.

PMID- 7814370
TI  - A novel mutagenesis strategy identifies distantly spaced amino acid sequences
      that are required for the phosphorylation of both the oligosaccharides of
      procathepsin D by N-acetylglucosamine 1-phosphotransferase.
AB  - A novel combinatorial mutagenesis strategy (shuffle mutagenesis) was developed to
      identify sequences in the propiece and amino lobe of cathepsin D which direct
      oligosaccharide phosphorylation by UDP-GlcNAc:lysosomal enzyme N
      acetylglucosamine 1-phosphotransferase. Propiece restriction fragments and
      oligonucleotide cassettes corresponding to 13 regions of the cathepsin D and
      glycopepsinogen amino lobes were randomly shuffled together to generate a large
      library of chimeric molecules. The library was inserted into an expression vector
      encoding the carboxyl lobe of cathepsin D with a carboxyl-terminal myc epitope
      and a CD8 transmembrane extension. Transfected COS1 cells expressing the membrane
      anchored forms of the cathepsin D/glycopepsinogen chimeras at the cell surface
      were selected with solid phase mannose 6-phosphate receptor or an antibody to the
      myc epitope. Plasmids were rescued in Escherichia coli and sequenced by
      hybridization to the original oligonucleotide cassettes. Two regions of the
      cathepsin D amino lobe (segments 7 and 12) were found to contribute to proper
      folding, surface expression, and selective phosphorylation of the carboxyl lobe
      oligosaccharide. Two different cathepsin D regions (the propiece and segment 5)
      cooperated with a previously identified recognition element in the carboxyl lobe
      to allow efficient phosphorylation of both the amino and carboxyl lobe
      oligosaccharides. Three general models for extending the catalytic reach of N
      acetylglucosamine 1-phosphotransferase to widely spaced oligosaccharides are
      presented.

PMID- 7814371
TI  - Isolation from rat kidney of a cytosolic high molecular weight cysteine-S
      conjugate beta-lyase with activity toward leukotriene E4.
AB  - A cytosolic high M(r) cysteine-S-conjugate beta-lyase (apparent M(r) of
      approximately 330,000) has been partially purified from rat kidneys. The high
      M(r) lyase is also present in the mitochondria. The purified enzyme contains at
      least two proteins with apparent M(r) values of approximately 50,000 and
      approximately 70,000. Activity is stimulated by dithiothreitol, alpha-keto acids,
      and pyridoxal 5'-phosphate; aminooxyacetate is an inhibitor. The enzyme catalyzes
      a competing (half) transamination reaction between pyridoxal 5'-phosphate
      cofactor and cysteine-S-conjugate substrate; added alpha-keto acids promote
      conversion of active site pyridoxamine 5'-phosphate to pyridoxal 5'-phosphate.
      The enzyme also catalyzes a full (but weak) transamination between L
      phenylalanine and alpha-keto-gamma-methiolbutyrate. The purified enzyme is not
      recognized by polyclonal rabbit antibodies to cytosolic rat kidney glutamine
      transaminase K (another cysteine-S-conjugate beta-lyase of rat kidney) and has no
      obvious similarities to other pyridoxal 5'-phosphate-containing enzymes. In
      addition to catalyzing elimination reactions with S-(1,2-dichlorovinyl)-L
      cysteine and S-(1,1,2,2-tetrafluoroethyl)-L-cysteine, the enzyme reacts with
      leukotriene E4 and 5'-S-cysteinyldopamine. Finally, the cytosolic and
      mitochondrial enzymes are activated by alpha-ketoglutarate. Thus, the possibility
      must be considered that, in kidneys of animals exposed to various cysteine
      conjugates, the high M(r) lyase contributes to the generation of pyruvate,
      ammonia, and reactive fragments in vivo. Many cysteine conjugates are
      nephrotoxic, and the high M(r) lyase(s) may be involved.

PMID- 7814372
TI  - The influence of cholesteryl ester transfer protein on the composition, size, and
      structure of spherical, reconstituted high density lipoproteins.
AB  - The effect of cholesteryl ester transfer protein (CETP) on the size, composition,
      and structure of spherical, reconstituted HDL (rHDL) which contain apolipoprotein
      (apo) A-I as their sole apolipoprotein has been studied. Spherical rHDL were
      incubated with CETP and Intralipid for up to 24 h. During this time CETP promoted
      transfers of cholesteryl esters (CE) and triglyceride (TG) between rHDL and
      Intralipid. As a result, the rHDL became depleted of CE and enriched in TG.
      However, as the loss of CE from the rHDL was greater than the gain of TG, the
      concentration of core lipids in the rHDL decreased. The decrease in the
      concentration of rHDL core lipids, which was evident throughout the incubation,
      was accompanied by a reduction in rHDL diameter from 9.2 to 8.0 nm, the
      dissociation of apoA-I from rHDL and a decrease in the number of apoA-I
      molecules, from three/particle in the 9.2-nm rHDL, to two/particle in the 8.0-nm
      rHDL. Spectroscopic studies showed that the lipid-water interface and
      phospholipid packing of the 8.0-nm rHDL were, respectively, more polar and less
      ordered than those of the 9.2-nm rHDL. Quenching studies with KI revealed that
      the number of exposed apoA-I Trp residues in the 9.2- and 8.0-nm rHDL was two and
      three, respectively. Circular dichroism established that the 9.2- and 8.0-nm rHDL
      had identical apoA-I alpha-helical contents. The 9.2- and 8.0-nm rHDL also had
      identical surface charges as determined by agarose gel electrophoresis.
      Denaturation studies with guanidine hydrochloride demonstrated that apoA-I is
      more stable in 8.0-nm rHDL than in 9.2-nm rHDL. It is concluded that CETP
      converts rHDL to small, TG-enriched, apoA-I-depleted particles with increased
      lipid-water interfacial hydration and less ordered phospholipid packing. These
      changes are associated with enhanced stability and minor changes to the
      conformation of the apoA-I which remains associated with the rHDL.

PMID- 7814373
TI  - Investigation of the influence of cytosine methylation on DNA flexibility.
AB  - To test the influence of pyrimidine methyl groups on DNA flexibility and helix
      repeat, two sets of 14 mixed sequence DNA molecules, spanning a range of lengths
      from 158 to 180 base pairs, were cyclized with T4 DNA ligase. The two sets
      differed only in that the Cyt-5 positions of all cytosines (80-90 cytosine
      residues per molecule) were fully methylated in the members of one set.
      Determination of the molar cyclization factors, persistence lengths, helix
      repeats, and torsional elastic constants revealed no significant differences
      between the two sets. These results imply that, at least for mixed sequence DNA,
      the biological consequences of cytosine methylation are likely to derive from
      either local structural distortions in the helix, which do not propagate as
      altered twist, or from direct protein-methyl cytosine interactions.

PMID- 7814374
TI  - Characterization of an autoinhibitory domain in human mitogen-activated protein
      kinase-activated protein kinase 2.
AB  - Mitogen-activated protein (MAP) kinase-activated protein kinase 2, a Ser/Thr
      kinase, is phosphorylated and activated by MAP kinase. Sequence analysis of a
      clone isolated from the human HL-60 cell line revealed a 370-amino acid protein
      with a proline-rich N terminus, a highly conserved catalytic domain, and a C
      terminal region containing a MAP kinase phosphorylation site. To better
      understand how the kinase is regulated, mutation analysis was used to map the
      functional domain(s). The wild type recombinant kinase had a low basal activity
      as detected by phosphorylation of a substrate peptide derived from the N terminus
      of glycogen synthase. Deletion of the proline-rich N terminus showed little
      effect on the basal activity. Deletion of the C terminus resulted in a marked
      increase in catalytic activity either with or without the pretreatment of the
      kinase by MAP kinase. Further analysis indicated that amino acid residues 339-353
      in the C-terminal region were acting as an autoinhibitory domain. A synthetic
      peptide (RVLKEDKERWEDVK-amide) derived from this autoinhibitory domain inhibited
      the kinase activity in a concentration-dependent manner. These results suggest a
      regulatory model for the kinase.

PMID- 7814375
TI  - Stable expression of a truncated AT1A receptor in CHO-K1 cells. The carboxyl
      terminal region directs agonist-induced internalization but not receptor
      signaling or desensitization.
AB  - Phosphorylation of serine and threonine residues in the carboxyl-terminal region
      of many G-protein-coupled receptors directs the rapid uncoupling from signal
      transduction pathways. In Chinese hamster ovary cells, we have stably expressed a
      truncated mutant of the angiotensin II (AT1A) receptor devoid of the carboxyl
      terminal 45 amino acids, encompassing 13 serine/threonine residues. One clone,
      designated TL314 to indicate truncation after leucine 314, expressed a single
      class of angiotensin II receptors with a dissociation constant of 1.08 nM and a
      receptor density of 560 fmol/mg of protein (approximately 75,000 receptors/cell).
      A nonhydrolyzable analog of GTP accelerated the angiotensin II-induced
      dissociation of [125I]angiotensin II from TL314 plasma membranes 3.6-fold,
      indicating G-protein coupling. In TL314 cells, angiotensin II stimulated the
      release of intracellular calcium and the induction of mitogen-activated protein
      kinase activity, the level of which were comparable with the full-length AT1A
      receptor. The AII-stimulated calcium response was rapidly desensitized in both
      full-length and truncated AT1A receptors. Interestingly, angiotensin II-induced
      endocytosis of the truncated receptor was almost completely inhibited, suggesting
      that a recognition motif within the carboxyl-terminal 45 amino acids of the AT1A
      receptor promotes sequestration. Thus, truncation of the AT1A receptor after
      leucine 314 inhibits agonist-induced internalization without affecting the
      capacity of the expressed protein to adopt the correct conformation necessary for
      high affinity binding of angiotensin II, coupling to G-proteins, and activation
      of signal transduction pathways. The rapid desensitization and refractoriness of
      the angiotensin II-induced calcium transient in the TL314 cell line, in which
      putative carboxyl-terminal phosphorylation sites are absent, suggests that the
      mechanism of AT1A receptor desensitization differs from that of other
      prototypical G-protein-coupled receptors.

PMID- 7814376
TI  - Different ARF domains are required for the activation of cholera toxin and
      phospholipase D.
AB  - ADP-ribosylation factors (ARFs), initially described as activators of cholera
      toxin ADP-ribosyltransferase activity, regulate intracellular vesicular membrane
      trafficking and stimulate a phospholipase D (PLD) isoform. ARF-like (ARL)
      proteins are structurally related to ARFs but do not activate cholera toxin and
      have relatively little effect on PLD. A new human ARL gene termed hARL1, which
      shares 57% amino acid identity with hARF1, was identified using a polymerase
      chain reaction-based cloning method. To determine whether different structural
      elements are responsible for the activation structural elements are responsible
      for the activation of the A subunit of cholera toxin and PLD, chimeric proteins
      were constructed by switching the amino-terminal 73 amino acids of ARF1 and ARL1.
      The recombinant rL73/F protein, in which the amino-terminal 73 amino acids of
      ARL1 replaced those of ARF1, activated the A subunit of cholera toxin, whereas
      the rF73/L protein, in which the NH2-terminal 73 amino acids of ARF1 replaced
      those of ARL1, was inactive. The two chimeric proteins had quite opposite effects
      on PLD activity. rF73/L activated PLD as effectively as rARF1, whereas rL73/F
      protein activated PLD only slightly. It appears that the amino-terminal region of
      ARF1 is not critical for its action as a GTP-dependent activator of cholera
      toxin, whereas it is necessary for activation of the putative effector enzyme,
      PLD.

PMID- 7814377
TI  - Inositol hexakisphosphate binds to clathrin assembly protein 3 (AP-3/AP180) and
      inhibits clathrin cage assembly in vitro.
AB  - We have isolated an inositol hexakisphosphate binding protein from rat brain by
      affinity elution chromatography from Mono S cation exchange resin using 0.1 mM
      inositol hexakisphosphate (InsP6). The amino acid sequences of six tryptic
      peptides from the protein were identical to the sequences predicted from the cDNA
      encoding a previously isolated protein designated as AP-3 or AP180. This protein
      is localized in nerve endings and promotes assembly of clathrin into coated
      vesicles. The isolated protein-bound InsP6 with a dissociation constant of 1.2
      microM and a stoichiometry of 0.9 mol of InsP6 bound/mol of AP-3. Recombinant AP
      3 expressed in Escherichia coli also bound InsP6 with a similar affinity. InsP6
      inhibited clathrin cage assembly mediated by AP-3, in an in vitro assay, but had
      little effect AP-3 binding to preformed cages. We speculate that InsP6 and
      perhaps highly phosphorylated inositol lipids may play a role in coated vesicle
      formation.

PMID- 7814378
TI  - Novel degradation pathway of glycated amino acids into free fructosamine by a
      Pseudomonas sp. soil strain extract.
AB  - A Pseudomonas sp. soil strain, selected for its ability to grow on epsilon-(1
      deoxyfructosyl) aminocaproic acid, was induced to express a membrane-bound
      enzymatic activity which oxidatively degrades Amadori products into free
      fructosamine. Apparent Km values for fructosyl aminocaproate, epsilon-fructosyl
      lysine, fructosyl glycine, and ribated lysine were 0.21 mM, 2.73 mM, 3.52 mM, and
      1.57 mM, respectively. The enzyme was also active against alpha-fructosyl lysine
      and borohydride-reduced Amadori product, weakly active with ribated and glycated
      polylysine, and inactive with reducing sugars, amino acids, and glycated
      proteins. The enzymatic activity was highest at pH 6.5 and 25 degrees C in 0.1 M
      sodium phosphate, while over 80% of the activity was lost above 65 degrees C.
      Complete inhibition was observed by HgCl2, NaN3, and NaCN suggesting a role for
      SH groups and copper in the enzymatic activity. The reaction products were
      characterized by 1H NMR, 13C NMR, and GC/MS and found to correspond to 1-deoxy-1
      aminofructose, i.e. free "fructosamine," and adipic acid. Confirmation of the
      free fructosamine structure was based on the complete spectroscopic identity of
      the borohydride reduction product with commercially available glucamine (1-amino
      1-deoxyglucitol). The new enzyme is provisorily classified as fructosyl N-alkyl
      amino acid oxidase (EC 1.5.3) (fructosyl-amino acid:oxygen oxidoreductase) and
      may thus belong to a novel class of "Amadoriases" which deglycate Amadori
      products oxidatively. In contrast, however, the new enzyme acts on the alkylamine
      bond rather than the ketoamine bond of the Amadori product.

PMID- 7814379
TI  - Assembly of the Photosystem II oxygen-evolving complex is inhibited in psbA site
      directed mutants of Chlamydomonas reinhardtii. Aspartate 170 of the D1
      polypeptide.
AB  - Photosystem II catalyzes the photooxidation of water to molecular oxygen,
      providing electrons to the photosynthetic electron transfer chain. The D1 and D2
      chloroplast-encoded reaction center polypeptides bind cofactors essential for
      Photosystem II function. Transformation of the chloroplast genome of the
      eukaryotic green alga Chlamydomonas reinhardtii has allowed us to engineer site
      directed mutants in which aspartate residue 170 of D1 is replaced by histidine
      (D170H), asparagine (D170N), threonine (D170T), or proline (D170P). Mutants D170T
      and D170P are completely deficient in oxygen evolution, but retain normal (D170T)
      or 50% (D170P) levels of Photosystem II reaction centers. D170H and D170N
      accumulate wild-type levels of PSII centers, yet evolve oxygen at rates
      approximately 45% and 15% those of control cells, respectively. Kinetic analysis
      of chlorophyll fluorescence in the mutants reveals a specific defect in electron
      donation to the reaction center. Measurements of oxygen flash yields in D170H
      show, however, that those reaction centers capable of evolving oxygen function
      normally. We conclude that aspartate residue 170 of the D1 polypeptide plays a
      critical role in the initial binding of manganese as the functional chloroplast
      oxygen-evolving complex is assembled.

PMID- 7814380
TI  - In male mouse germ cells, copper-zinc superoxide dismutase utilizes alternative
      promoters that produce multiple transcripts with different translation potential.
AB  - Copper-zinc superoxide dismutase (SOD-1) is an enzyme that is widely expressed in
      eukaryotic cells and performs a vital role in protecting cells against free
      radical damage. In mouse testis, three different sizes of SOD-1 mRNAs of about
      0.73, 0.80, and 0.93 kilobases (kb) are detected. The 0.73-kb mRNA is found in
      early stages of male germ cells and in all somatic tissues. The mRNAs of 0.80 and
      0.93 kb are exclusively detected in post-meiotic germ cells. RNase H digestions
      and Northern blot analyses reveal that the three SOD-1 mRNAs are derived from two
      transcripts, a ubiquitously expressed transcript and a post-meiotic transcript,
      which differ by 114-120 nucleotides. RNase protection assays demonstrate that the
      additional nucleotides present in the post-meiotic mRNA are solely in the 5'
      untranslated region. Using a probe derived from the 5'-untranslated region of the
      0.93-kb SOD-1 mRNA, we have established that it originates from an alternative
      upstream promoter contiguous with the somatic SOD-1 promoter. Polysomal gradient
      analysis of the three mouse testis SOD-1 mRNAs reveals that the 0.93-kb SOD-1
      mRNA is primarily non-polysomal, while the 0.80- and 0.73-kb SOD-1 mRNAs are
      mostly polysome associated. A faster migrating form of the 0.93-kb SOD-1 mRNA is
      present on polysomes as a result of partial deadenylation. In a cell-free
      translation system, the 0.73-kb SOD-1 mRNA translates about 2-fold more
      efficiently than the 0.93-kb SOD-1 mRNA. These data demonstrate that male germ
      cells transcribe two size classes of SOD-1 mRNAs with different translation
      potential by utilizing two different promoters, post-meiotic SOD-1 mRNAs undergo
      adenylation changes, and one of the post-meiotic SOD-1 mRNAs is transcribed
      during mid-spermiogenesis and translated days later in a partially deadenylated
      form.

PMID- 7814381
TI  - Saccharomyces cerevisiae CNE1 encodes an endoplasmic reticulum (ER) membrane
      protein with sequence similarity to calnexin and calreticulin and functions as a
      constituent of the ER quality control apparatus.
AB  - We have used a polymerase chain reaction strategy to identify in the yeast
      Saccharomyces cerevisiae genes of the mammalian calnexin/calreticulin family, and
      we have identified and isolated a single gene, CNE1. The protein predicted from
      the CNE1 DNA sequence shares some of the motifs with calnexin and calreticulin,
      and it is 24% identical and 31% similar at the amino acid level with mammalian
      calnexin. On the basis of its solubility in detergents and its lack of extraction
      from membranes by 2.5 M urea, high salt, and sodium carbonate at pH 11.5, we have
      established that Cne1p is an integral membrane protein. However, unlike
      calnexins, the predicted carboxyl-terminal membrane-spanning domain of Cne1p
      terminates directly. Furthermore, based on its changed mobility from 76 to 60 kDa
      after endoglycosidase H digestion Cne1p was shown to be N-glycosylated.
      Localization of the Cne1p protein by differential and analytical subcellular
      fractionation as well as by confocal immunofluorescence microscopy showed that it
      was exclusively located in the endoplasmic reticulum (ER), despite the lack of
      known ER retention motifs. Although six Ca(2+)-binding proteins were detected in
      the ER fractions, they were all soluble proteins, and Ca2+ binding activity has
      not been detected for Cne1p. Disruption of the CNE1 gene did not lead to inviable
      cells or to gross effects on the levels of secreted proteins such as alpha
      pheromone or acid phosphatase. However, in CNE1 disrupted cells, there was an
      increase of cell-surface expression of an ER retained temperature-sensitive
      mutant of the alpha-pheromone receptor, ste2-3p, and also an increase in the
      secretion of heterologously expressed mammalian alpha 1-antitrypsin. Hence, Cne1p
      appears to function as a constituent of the S. cerevisiae ER protein quality
      control apparatus.

PMID- 7814382
TI  - The sequence of porcine protein NH2-terminal asparagine amidohydrolase. A new
      component of the N-end Rule pathway.
AB  - Co- and post-translational amino-terminal processing of proteins is one mechanism
      by which intracellular proteins can be either protected from or targeted to
      degradation by the N-end Rule pathway (Bachmair, A., Finley, D., and Varshavsky,
      A. (1986) Science 234, 179-186). A novel enzyme, protein NH2-terminal asparagine
      amidohydrolase, which can function in this pathway by potentially directing
      critical regulatory proteins possessing an amino-terminal asparagine residue
      formed from the removal of N-acetylmethionine, has recently been purified and
      characterized (Stewart, A.E., Arfin, S. M., and Bradshaw, R. A. (1994) J. Biol.
      Chem. 269, 23509-23517). Here, we report the isolation and characterization of a
      cDNA for porcine protein NH2-terminal asparagine amidohydrolase, which indicates
      that it is a new type of enzyme, not homologous to any previously identified
      protein. This provides strong evidence for the importance of regulated protein
      degradation in cellular functioning.

PMID- 7814383
TI  - Differential mitotic phosphorylation of proteins of the nuclear pore complex.
AB  - During each cell cycle, the nucleus of higher eukaryotes undergoes a dramatic
      assembly and disassembly. These events can be faithfully reproduced in vitro
      using cell-free extracts derived from Xenopus eggs. Such extracts contain three
      major N-acetylglucosaminylated proteins, p200, p97, and p60. All three become
      assembled into reconstituted nuclear pores. Here we show that p200, p97, and p60
      exist in eggs in soluble high molecular mass complexes of 1000, 450, and 600 kDA,
      respectively. The bulk of p60 is stably associated with proteins of 58 and 54
      kDa, while p200 is associated with a fraction of p60 in a separate complex
      lacking p58 and p54. Upon examining the behavior of these proteins in the cell
      cycle, we find that p200 and p97 are highly phosphorylated at mitosis, both in
      vivo and in vitro. Moreover, in extracts that cycle between interphase and
      mitosis, p200 and p97 are specifically phosphorylated at mitosis. Corresponding
      with their mitotic phosphorylation, both p200 and p97 are specific substrates for
      purified mitotic Cdc2 kinase, whereas nucleoporin p60 is not. Analysis indicates
      that the size of the complexes containing the pore N-acetylglucosamine
      glycoproteins does not change during mitosis, suggesting that such complexes
      represent stable multicomponent modules into which the nucleus disassembles at
      mitosis.

PMID- 7814384
TI  - A structure-function study of bovine pancreatic phospholipase A2 using
      polymerized mixed liposomes.
AB  - A new combinatorial approach that includes the genetic variation of protein
      structure and the chemical modification of phospholipid structure in polymerized
      mixed liposomes was used to delineate the structure-function relationships in the
      interfacial catalysis of bovine pancreatic phospholipase A2 (PLA2). Based on
      previous structural and mutational studies, several bovine PLA2 mutants were
      generated in which a positive charge of putatively important lysyl side chains
      was reversed (K10E, K53E, K56E, and K116E) or neutralized (K56Q and K116Q).
      Kinetic parameters of bovine wild type and mutant PLA2s determined using
      polymerized mixed liposomes consisting of 1-hexadecanoyl-2-(1-pyrenedecanoyl)-sn
      glycero-3-phosphoethanolamine (or -phosphoglycerol) and 1,2-bis[12
      (lipoyloxy)dodecanoyl]-sn-glycero-3-phosphoglycerol showed that Lys-53 is
      involved specifically in the interaction with a substrate bound in the active
      site. Also, these results showed that Lys-10 and Lys-116 are involved in the
      interaction of bovine PLA2 with anionic interfaces but not in the interaction
      with the active site-bound substrate. In particular, Lys-116 makes more
      significant contribution than Lys-10 by approximately 1.0 kcal/mol to the binding
      to anionic interfaces. Most importantly, Lys-56 was shown to participate in the
      interaction with both the active site-bound substrate and anionic interfaces.
      These findings establish Lys-56 and Lys-116 as essential residues for the binding
      of bovine pancreatic PLA2 to anionic interfaces. Lastly, our structure-function
      analysis based on the use of polymerized mixed liposomes was further supported by
      equilibrium binding measurements of these proteins using 1,2-bis[12
      (lipoyloxy)dodecanoyl]-sn-glycero-3-phosphoglycerol polymerized liposomes and by
      kinetic analyses using monomeric substrates, 1,2-dihexanoyl-sn-glycero-3
      phosphoethanolamine and -phosphoglycerol.

PMID- 7814385
TI  - Matrix/integrin interaction activates the mitogen-activated protein kinase,
      p44erk-1 and p42erk-2.
AB  - Cell adhesion to extracellular matrix proteins is a dynamic process leading to
      dramatic changes in the cell phenotype. Integrins are one of the major receptor
      families that mediate cell-matrix contact. Evidence that integrins can act as
      signal transducing molecules has accumulated over the past few years. We report
      here that p44erk-1 and p42erk-2 mitogen-activated protein (MAP) kinases are
      rapidly phosphorylated on tyrosine residues upon adhesion of human skin
      fibroblasts to fibronectin or upon cross-linking of beta 1 integrins with
      antibody. The tyrosine phosphorylation of both kinases is associated with
      increased enzymatic activity. Pretreatment of the cells with cytochalasin D,
      which selectively disrupts the network of the actin filaments, completely
      inhibits this adhesion-mediated MAP kinase activation. Thus, our findings
      indicate that ligation of beta 1 integrins induces an increase in both tyrosine
      phosphorylation and enzymatic activity of p44erk-1 and p42erk-2 MAP kinases, and
      that the integrity of the actin cytoskeleton is essential in this process. Since
      MAP kinase behaves as a convergence point for diverse receptor-initiated
      signaling events at the plasma membrane, this serine/threonine kinase plays a key
      role and helps to account for the diversity of integrin-dependent cell functions.

PMID- 7814386
TI  - Mechanism of inhibition of human nonpancreatic secreted phospholipase A2 by the
      anti-inflammatory agent BMS-181162.
AB  - Many important mediators of inflammation result from the liberation of free
      arachidonic acid from phospholipid pools which is thought to result from the
      action of phospholipase A2 (PLA2). It is believed, therefore, that the inhibition
      of PLA2 would be an important treatment in many inflammatory disease states. The
      anti-inflammatory agent BMS-181162 (4-(3'-carboxyphenyl)-3,7-dimethyl-9-(2",6",6"
      trimethyl-1"-cyclohexenyl )-2Z,4E , 6E,8E-nonatetraenoic acid) selectively
      inhibits PLA2 and has been shown to block arachidonic acid release in whole
      cells. The mechanism of inhibition of human non-pancreatic-secreted PLA2 by BMS
      181162 is investigated in this paper. A scooting mode assay in which the enzyme
      is irreversibly bound to vesicles of 1,2-dimyristoyl-sn-glycero-3-phosphomethanol
      containing 5 mol % of 1-palmitoyl-2-[1-14C]arachidonoyl-sn-glycero-3
      phosphocholine, was used to characterize the inhibition. With this assay system,
      BMS-181162 inhibited the enzyme in a dose-dependent manner. Compounds which
      inhibit in the scooting mode have been shown to be competitive inhibitors in the
      interface (Gelb, M. H., Berg, O., and Jain, M. K. (1991) Curr. Op. Struct. Biol.
      1, 836-843). This was verified by demonstrating that the inhibition was not due
      to the desorption of the enzyme from the lipid-water interface. Additionally, the
      compound did not measurably affect the rate of association onto the vesicles.
      Therefore, the inhibition was not the result of a modulation of the bilayer
      morphology nor an interaction with the interfacial binding site on the enzyme.
      The degree of inhibition was dependent on the reaction volume which indicates
      that the inhibitor is only partially partitioned into the bilayer. After
      compensating for this partitioning, the dose-dependent inhibition could be
      defined by kinetic equations describing competitive inhibition at the interface.
      The equilibrium dissociation constant for the inhibitor bound to the enzyme at
      the interface (KI*) was determined to be 0.013 mol fraction, thus demonstrating
      that BMS-181162 represents a novel structural class of tight-binding competitive
      inhibitors of human nonpancreatic secreted PLA2. Using Escherichia coli membranes
      as substrate, to which the enzyme binds to the interface reversibly, the
      inhibition showed a nonclassical kinetic pattern which is also consistent with a
      partial partitioning of the inhibitor into the bilayer. This was verified by a
      direct measurement of the amount of inhibitor remaining in solution. The
      implications for in vivo efficacy which result from this mechanism are discussed.

PMID- 7814387
TI  - Lophotoxin is a slow binding irreversible inhibitor of nicotinic acetylcholine
      receptors.
AB  - Lophotoxin and the bipinnatins are members of the lophotoxin family of marine
      neurotoxins, which covalently react with Tyr190 in the alpha-subunits of the
      nicotinic acetylcholine receptor. Bipinnatin-A, -B, and -C are protoxins that
      have been shown to spontaneously convert from inactive to active toxins during
      preincubation in buffer. However, in this report, we show that preincubation of
      lophotoxin did not result in an increase in the subsequent rate of irreversible
      inhibition of nicotinic receptors. Thus, unlike the bipinnatins, lophotoxin does
      not appear to be an inactive protoxin. Lophotoxin preferentially inhibited one of
      the two acetylcholine-binding sites on the receptor, and this preference resulted
      from both a higher reversible affinity and a faster rate of irreversible
      inhibition at this site. Association of 125I-alpha-bungarotoxin in the presence
      of lophotoxin was analyzed to obtain the apparent reversible association and
      dissociation rate constants for lophotoxin. The apparent association rate
      constant of lophotoxin was approximately 10(6)-fold slower than expected for a
      diffusion-limited interaction, indicating that lophotoxin is a slow binding
      irreversible inhibitor. The kinetic constants that describe the interaction of
      lophotoxin with the receptor did not change in the presence of dibucaine,
      suggesting that, unlike agonists, the slow apparent association of lophotoxin
      does not result from a slow transition of the receptor to a desensitized
      conformation.

PMID- 7814388
TI  - Mannose 6-phosphate/insulin-like growth factor II receptor fails to interact with
      G-proteins. Analysis of mutant cytoplasmic receptor domains.
AB  - The binding of insulin-like growth factor II (IGF II) to the mannose 6-phosphate
      (M6P)/IGF II receptor has previously been reported to induce the activation of
      trimeric G(i)2 proteins by functional coupling to a 14-amino acid region within
      the cytoplasmic receptor domain (Nishimoto, I., Murayama, Y., Katada, T., Ui, M.,
      and Ogata, E. (1989) J. Biol. Chem. 264, 14029-14038). In the present study, we
      examined further the potential functional coupling of G-proteins with the human
      M6P/IGF II receptor and mutant receptors lacking the proposed G-protein activator
      sequence. IGF II treatment of mouse L-cells expressing either wild type or mutant
      M6P/IGF II receptors failed to attenuate the pertussis toxin-catalyzed
      modification of a 40-kDa protein or enhance GTPase activity. In broken L-cell
      membranes expressing wild type or mutant M6P/IGF II receptors, 30 nM IGF II also
      failed to affect the pertussis toxin substrate activity. By using phospholipid
      vesicles reconstituted with human wild type or mutant M6P/IGF II receptors and
      pertussis toxin-sensitive G-proteins, no stimulation of GTP gamma S binding to or
      GTPase activity of G(i)2, G(o)1, or G(i)/G(o) mixtures were observed in response
      to 1 microM IGF II. Furthermore, in vesicles containing purified wild type
      M6P/IGF II receptors and monomeric G alpha o1 or G alpha i2 and beta gamma dimers
      no effects of IGF II on GTP gamma S binding could be detected. However, when
      vesicles reconstituted with M6P/IGF II receptors and G(i)2 proteins were
      incubated with 100 microM mastoparan GTP gamma S binding was stimulated and
      GTPase activity was increased significantly. These results indicate that the
      human M6P/IGF II receptor neither interacts with G-proteins in mouse L-cell
      membranes nor is coupled to G(i)2 proteins in phospholipid vesicles. This study
      suggests strongly that the M6P/IGF II receptor does not function in transmembrane
      signaling in response to IGF II.

PMID- 7814389
TI  - Degradation of a calcium influx factor (CIF) can be blocked by phosphatase
      inhibitors or chelation of Ca2+.
AB  - In many cell types, depletion of Ca2+ stores causes activation of Ca2+ influx by
      a mechanism whose molecular basis remains unclear. We recently described a new
      messenger that is released by empty Ca2+ stores and that activates Ca2+ influx in
      heterologous cells (Randriamampita, C. & Tsien, R. Y. (1993) Nature 364, 809
      814). This factor, provisionally named CIF (for Ca2+ influx factor), seems to be
      a small nonprotein factor possessing a phosphate group. Meanwhile Parekh et al.
      reported that okadaic acid, an inhibitor of protein phosphatases 1 and 2A,
      potentiates Ca2+ influx in Xenopus oocytes (Parekh, A. B., Terlau, H. & Stuhmer,
      W. (1993) Nature 364, 814-818). A link between these two observations is
      presented in this paper. We show that in astrocytoma cells, okadaic acid and
      cyclosporin A (an inhibitor of calcineurin) both potentiate the Ca2+ elevations
      due to low doses of CIF, thapsigargin, or carbachol. In lymphocytes, okadaic acid
      potentiates the Ca2+ elevations due to low doses of phytohemagglutinin and
      increases the amount of extractable CIF. CIF degradation can be observed in cell
      free homogenates of lymphocytes and is prevented by the above phosphatase
      inhibitors, an effect that can at least partly explain their potentiation of Ca2+
      influx. CIF degradation is also prevented by lowering free Ca2+ concentrations,
      which could be a feedback mechanism to enhance Ca2+ influx when cells are
      depleted of Ca2+.

PMID- 7814390
TI  - Secondary structure of uracil-DNA glycosylase inhibitor protein.
AB  - The Bacillus subtilis bacteriophage PBS2 uracil-DNA glycosylase inhibitor (Ugi)
      is an acidic protein of 84 amino acids that inactivates uracil-DNA glycosylase
      from diverse organisms (Wang, Z., and Mosbaugh, D. W. (1989) J. Biol. Chem. 264,
      1163-1171). The secondary structure of Ugi has been determined by solution state
      multidimensional nuclear magnetic resonance. The protein adopts a single well
      defined structure consisting of five anti-parallel beta-strands and two alpha
      helices. Six loop or turn regions were identified that contain approximately one
      half of the acidic amino acid residues and connect the beta-strands sequentially
      to one another. The secondary structure suggests which regions of Ugi may be
      involved in interactions with uracil-DNA glycosylase.

PMID- 7814391
TI  - Direct measurement of nitric oxide generation in the ischemic heart using
      electron paramagnetic resonance spectroscopy.
AB  - Nitric oxide, NO., exerts numerous important regulatory functions in biological
      tissues and has been hypothesized to have a role in the pathogenesis of cellular
      injury in a number of diseases. It has been suggested that alterations in NO.
      generation are a critical cause of injury in the ischemic heart. However, the
      precise alterations in NO. generation which occur are not known, and there is
      considerable controversy regarding whether myocardial ischemia results in
      increased or decreased NO. formation. Therefore, electron paramagnetic resonance
      studies were performed to directly measure NO. in isolated rat hearts subjected
      to global ischemia, using the direct NO. trap Fe(2+)-N-methyl-D-glucamine
      dithiocarbamate, which specifically binds NO. giving rise to a characteristic
      triplet EPR spectrum with g = 2.04 and aN = 13.2 G. While only a small triplet
      signal was observed in normally perfused hearts, a 10-fold increase in this
      triplet EPR spectrum was observed after 30 min of ischemia indicating a marked
      increase in NO. formation and trapping. Measurements were performed as a function
      of the duration of ischemia, and it was determined that with increased duration
      of ischemia NO. formation and trapping was also increased. NO. generation was
      inhibited by the nitric oxide synthase blocker, N-nitro-L-arginine methyl ester
      (L-NAME), suggesting that NO. was generated via nitric oxide synthase. Blockade
      of NO. generation with L-NAME resulted in more than a 2-fold increase in the
      recovery of contractile function in hearts reperfused after 30 min of global
      ischemia. Thus, ischemia causes a marked duration-dependent increase of NO. in
      the heart which may in turn mediate postischemic injury.

PMID- 7814393
TI  - Binding characteristics of ciliary neurotrophic factor to sympathetic neurons and
      neuronal cell lines.
AB  - Ciliary neurotrophic factor (CNTF) is a cytokine whose actions are largely
      restricted to the nervous system because of the predominant neuronal distribution
      of its receptor, CNTFR alpha. In this study, we sought to define the binding
      characteristics of CNTF to cultured sympathetic neurons and cell lines of
      neuronal origin. We report that 125I-CNTF binds to cultured sympathetic neurons,
      MAH, PC12, and EW-1 cells via high and low affinity receptors that can be
      distinguished on the basis of their dissociation constants (KD1 approximately 10(
      12) M and KD2 approximately 10(-9) M). Competition experiments showed that the
      IC50 for rat and human CNTF were, respectively, 65 pM and 5 nM for sympathetic
      neurons and 75 pM and 1.2 nM for EW-1 cells. Interestingly, leukemia inhibitory
      factor (LIF) did not compete for CNTF binding even at 100 nM concentration. The
      binding of 125I-CNTF to sympathetic neurons involved all three components of the
      CNTF receptor complex, namely CNTFR alpha, LIFR, and gp130, as shown by cross
      linking experiments. CNTF and LIF treatments down-regulated CNTF binding to
      sympathetic neurons and EW-1 cells, suggesting that heterologous ligands can
      regulate CNTF receptor levels, which may in turn modulate the efficacy of CNTF in
      vitro and in vivo.

PMID- 7814392
TI  - Induction of vascular endothelial growth factor gene expression by interleukin-1
      beta in rat aortic smooth muscle cells.
AB  - Vascular endothelial growth factor (VEGF) is a potent and specific mitogen for
      vascular endothelial cells and promotes neovascularization in vivo. To determine
      whether interleukin-1 beta (IL-1 beta), which is present in atherosclerotic
      lesions, induces VEGF gene expression in vascular smooth muscle cells, we
      performed RNA blot analysis on rat aortic smooth muscle cells (RASMC) with a rat
      VEGF cDNA probe. IL-1 beta increased VEGF mRNA levels in RASMC in a time- and
      dose-dependent manner. As little as 0.1 ng/ml IL-1 beta increased VEGF mRNA
      levels by 2-fold and 10 ng/ml IL-1 beta increased VEGF mRNA by 4-fold. We also
      measured the half-life of VEGF mRNA and performed nuclear run-on experiments
      before and after addition of IL-1 beta to see if IL-1 beta increased VEGF mRNA
      levels by stabilizing the mRNA or by increasing its rate of transcription. The
      normal, 2-h half-life of VEGF mRNA in RASMC was lengthened to 3.2 h (60%) by IL-1
      beta, and IL-1 beta increased the rate of VEGF gene transcription by 2.1-fold. In
      immunoblot experiments with an antibody specific for VEGF, we found that IL-1
      beta increased VEGF protein levels in RASMC by 3.3-fold. Together these data
      indicate that IL-1 beta induces VEGF gene expression in smooth muscle cells. This
      IL-1 beta-induced expression of VEGF may accelerate the progression of
      atherosclerotic lesions by promoting the development of new blood vessels.

PMID- 7814394
TI  - Calcium regulation of calcineurin phosphatase activity by its B subunit and
      calmodulin. Role of the autoinhibitory domain.
AB  - Calcineurin (CaN) contains an autoinhibitory element (residues 457-482) 43
      residues COOH-terminal of the calmodulin-binding domain (Hashimoto, Y., Perrino,
      B. A., and Soderling, T. R. (1990) J. Biol. Chem. 265, 1924-1927) that regulates
      the Ca(2+)-dependent activation of its phosphatase activity. Substitution of
      Arg476 and Arg477 or Asp467 to Ala in the autoinhibitory peptide 457-482
      significantly decreased its inhibitory potency. CaN A subunits with these
      residues mutated to Ala were coexpressed with the Ca(2+)-binding B subunit using
      the baculovirus/Sf9 cell system. Kinetic analysis showed that although the
      purified mutants had no activity in the absence of calcium, they were less
      dependent than the wild-type enzyme on calcium and calmodulin for activity. To
      determine if additional autoinhibitory motifs were present in the COOH terminus
      of calcineurin, the A subunit was truncated at residues 457 or 420 and co
      expressed with B subunit. The Vmax values of both truncation mutants with or
      without Ca2+ were increased relative to wild-type calcineurin. The increased
      Ca(2+)-independent activity of CaN420 relative to CaN457 indicates the presence
      of additional autoinhibitory element(s) within residues 420-457. CaN420 had
      similar high Vmax values with or without Ca2+, but the Km value for peptide
      substrate was increased 5-fold to 125 microM in the absence of Ca2+. The Km
      values of all the expressed calcineurin species were increased in the absence of
      Ca2+. The CaN A or CaN A420 subunits alone have low Vmax and high Km (115 microM)
      values even in the presence of Ca2+. These results indicate that 1) there are
      several autoinhibitory motifs between the CaM-binding domain and the COOH
      terminus that are relieved by Ca2+ binding to CaM and the B subunit, 2) Ca2+
      binding to the B subunit also regulates enzyme activity by lowering the Km of the
      catalytic subunit for substrate, 3) binding of the B subunit is required for high
      Vmax values even after removal of the autoinhibitory domain. These results are
      consistent with synergistic activation of calcineurin by Ca2+ acting through both
      CaM and the B subunit.

PMID- 7814395
TI  - Isolation and characterization of a novel collagen-binding protein from
      Streptococcus pyogenes strain 6414.
AB  - In this report we have analyzed the binding of collagen to Streptococcus pyogenes
      strain 6414. This binding was rapid, specific, and involved a limited number of
      receptor molecules (11,600 copies per cell). When the proteins in a streptococcal
      lysate were blotted onto a nitrocellulose filter and probed with 125I-labeled
      collagen, a prominent collagen-binding protein of 57 kDa was identified as well
      as minor 130-150-kDa components. The major 57-kDa protein was isolated by
      affinity chromatography on collagen-Sepharose followed by gel filtration
      chromatography. The 57-kDa protein purified from S. pyogenes was used to raise a
      monospecific antibody which also reacted with a collagen-binding protein of
      similar molecular size isolated from Streptococcus zooepidemicus. The two
      collagen-binding proteins from streptococci have a similar amino acid composition
      and isoelectric points. Isolated collagen-binding protein was specifically
      recognized by 125I-collagen in a solid-phase binding assay and displayed an
      affinity for the ligand quite similar to that exhibited by intact bacteria (Kd =
      3.1 versus 3.5 x 10(-9) M, respectively). Surface-labeled bacteria attached to
      microtiter wells coated with different collagen types and the 57-kDa protein
      blocked the adhesion to collagen substrate. We propose that the 57-kDa protein is
      an adhesin involved in the attachment of streptococci to host tissues.

PMID- 7814396
TI  - Identification of the nuclear localization signal of rat liver CTP:phosphocholine
      cytidylyltransferase.
AB  - CTP:phosphocholine cytidylyltransferase (CT) is a major regulatory enzyme in
      phosphatidylcholine synthesis in mammalian cells. CT is found in both soluble and
      particulate forms, both of which are nuclear. We report here the identification
      of a 21-residue sequence at the amino terminus of CT, 8KVNSRKRRKEVPGPNGATEED28,
      which was sufficient to direct beta-galactosidase into the cell nucleus. Further
      deletions from either end of this sequence greatly reduced the nuclear
      localization of beta-galactosidase. Deletions of amino acids within the nuclear
      localization signal or of the entire signal disrupted CT nuclear localization,
      but CT was not completely excluded from the nucleus. Clones of stable
      transfectants of the nuclear localization signal-deficient CT expressed in
      Chinese hamster ovary (CHO) 58 cells, which is temperature-sensitive for growth
      and CT activity, were isolated and characterized. The deletion mutants were
      active under the same conditions as the wild-type enzyme. Despite the difference
      in subcellular location from wild-type CT, the nuclear localization mutants were
      fully able to complement the CT-deficient cell line CHO 58 for both growth and
      choline incorporation into phosphatidylcholine at the nonpermissive temperature.
      The mobility of the mutant enzymes on SDS gels was altered relative to the
      mobility of wild-type CT; however, the extent of phosphorylation of the mutant
      enzymes was decreased only slightly. Thus, the distribution of CT in both
      cytoplasm and nucleus, rather than exclusively nucleus, has little effect on the
      ability of CT to function in growing CHO cells.

PMID- 7814397
TI  - Alcohol:NAD+ oxidoreductase is present in rat liver peroxisomes.
AB  - Alcohol:NAD+ oxidoreductase was found in the peroxisomes of animal liver for the
      first time as follows. The distribution of alcohol:NAD+ oxidoreductase activity
      with nonanol as substrate in the light mitochondrial fraction (peroxisome
      enriched fraction) of rat liver was examined by centrifugation in a sucrose
      density gradient. Most of the enzyme activity was localized in the mitochondria,
      with some activity in the peroxisomes. The administration of clofibrate, a
      peroxisome proliferator, to rats resulted in a marked increase of the enzyme
      activity in the peroxisomes, but not in the mitochondria. The enzyme was found to
      be located in the matrix of the peroxisomes. The evidence was obtained that the
      enzyme differed from alcohol dehydrogenases and alcohol oxidizing systems found
      previously. The enzyme activity was not affected by pyrazole, an inhibitor of
      alcohol dehydrogenase and sodium azide, an inhibitor of catalase. The enzyme was
      NAD(+)-dependent and oxidized straight chain aliphatic alcohols with a variety of
      carbon chains (C2-C18), showing the maximum on nonanol. Km values toward these
      aliphatic alcohols decreased with increasing chain length. The major reaction
      product was identified as the carboxylic acid by using high performance liquid
      chromatography.

PMID- 7814398
TI  - Purification of deoxyhypusine synthase from Neurospora crassa to homogeneity by
      substrate elution affinity chromatography.
AB  - Deoxyhypusine synthase is an NAD(+)-dependent enzyme that catalyzes the formation
      of deoxyhypusine residue on the eIF-5A precursor by using spermidine as the
      substrate. Deoxyhypusine synthase bound tightly to 1,12-diaminododecane-agarose
      and could be eluted selectively by spermidine. This finding enabled us to develop
      a simple two-column procedure to purify deoxyhypusine synthase from Neurospora
      crassa to apparent homogeneity. The purified enzyme had a specific activity of
      130,000 units/mg of protein, representing a 64,000-fold purification from cell
      extracts. Size exclusion chromatography indicated that the native enzyme had a
      molecular mass of 180 kDa. Sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis of the pure enzyme showed a single band at the 40-kDa position,
      suggesting that Neurospora deoxyhypusine synthase is a homotetramer.
      Deoxyhypusine synthase appeared to be hydrophobic and required non-ionic
      detergent such as Tween 20 to stabilize the activity. Treatment of the enzyme
      with sulfhydryl reagents resulted in a complete loss of activity. Inclusion of
      NAD+ reduced the inactivation rate by manyfold, indicating the presence of -SH
      groups at or near the active site. Partial amino acid sequences of four peptide
      fragments that cover about one quarter of the enzyme were obtained for cDNA and
      genomic cloning work.

PMID- 7814399
TI  - Interferon-gamma-mediated inactivation of transcription of the 230-kDa bullous
      pemphigoid antigen gene (BPAG1) provides novel insight into keratinocyte
      differentiation.
AB  - Interferon-gamma (IFN-gamma) has been shown to regulate epidermal keratinocyte
      growth and differentiation. In this study, we examined the effects of recombinant
      human IFN-gamma on the expression of the gene encoding the 230-kDa bullous
      pemphigoid antigen (BPAG1), a marker of the mitotic basal cell phenotype in the
      epidermis. Northern analysis revealed a dose- and time-dependent suppression of
      BPAG1 expression by IFN-gamma in cultured human keratinocytes from several
      different donors, and incubation of the cells with IFN-gamma in the presence of
      cycloheximide demonstrated that this effect required ongoing protein synthesis.
      The inhibition of BPAG1 gene expression was also demonstrated at the protein
      level by indirect immunofluorescence using a monoclonal antibody recognizing the
      human 230-kDa bullous pemphigoid antigen. Transient transfections of cultured
      keratinocytes with BPAG1 promoter-chloramphenicol acetyltransferase reporter gene
      plasmids indicated marked suppression of the promoter activity by IFN-gamma, and
      deletion constructs were able to identify a defined region containing the
      responsive element (IFN-gamma inhibitory element). Reduced transcription of the
      BPAG1 gene by IFN-gamma was also demonstrated by in vitro nuclear run-on assays.
      These data, which indicate inactivation of transcription of a basal keratinocyte
      specific gene of transcription of a basal keratinocyte-specific gene (BPAG1) by
      IFN-gamma, provide novel insight into the mechanisms of IFN-gamma-mediated
      keratinocyte gene regulation and epidermal differentiation in inflammatory
      diseases.

PMID- 7814400
TI  - Transcriptional regulation of the interferon-gamma-inducible tryptophanyl-tRNA
      synthetase includes alternative splicing.
AB  - We have investigated the transcriptional control elements of the human interferon
      (IFN)-gamma-induced tryptophanyl-tRNA synthetase (hWRS) gene and characterized
      the transcripts. Transcription leads to a series of mRNAs with different
      combinations of the first exons. The full-length mRNA codes for a 55-kDa protein
      (hWRS), but a mRNA lacking exon II is present in almost as high amounts as the
      full-length transcript. This alternatively spliced mRNA is probably translated
      into a 48-kDa protein starting from Met48 in exon III. The predicted 48-kDa
      protein corresponds exactly to an IFN-gamma-inducible protein previously detected
      by two-dimensional gel electrophoresis. By isolation of genomic clones and
      construction of plasmids containing hWRS promoter fragments fused to the secreted
      alkaline phosphatase reporter gene we have mapped a promoter region essential for
      IFN-mediated gene activation. This region contains IFN-stimulated response
      elements (ISRE) as well as a Y-box and a gamma-activated sequence (GAS) element.
      IFN-gamma inducibility of hWRS depends on ongoing protein synthesis, suggesting
      that so far undescribed transcription factors apart from the latent GAS-binding
      protein p91 contribute to gene activation. This could be interferon-regulatory
      factor-1, which binds ISRE elements.

PMID- 7814401
TI  - Recombinant domain III of perlecan promotes cell attachment through its RGDS
      sequence.
AB  - Perlecan has been previously been shown to support attachment of a wide variety
      of cells through interactions of its core protein with the cell surface. The core
      protein domains involved in cell adhesion are, however, unknown. The laminin-like
      domain III of murine perlecan contains an RGDS sequence and is a likely candidate
      for supporting integrin-mediated cell attachment. We made a cDNA construct
      corresponding to domain III and containing an in frame signal peptide at the 5'
      end as well as in frame a stop codon at the 3' end by using cDNA clones to
      perlecan. The construct was inserted into the pRC/CMV vector and transfected into
      HT1080 cells, and the secreted recombinant domain III, a 130-kDa protein, was
      purified from the medium. The size of proteolytic fragments produced by digestion
      with V8 protease as well as analysis of the rotary shadowed image of the
      recombinant protein indicated it was produced in a native conformation.
      Recombinant domain III coated on tissue culture dishes, supports adhesion of an
      epithelial-like mouse mammary tumor cell line MMT 060562 in a dose-dependent
      manner. This interaction was inhibited specifically by the RGDS synthetic peptide
      and intact perlecan, but not laminin. This domain III RGD-dependent cell
      attachment activity indicates a role for perlecan in integrin-mediated signaling.

PMID- 7814402
TI  - Gene structure of the murine N-methyl D-aspartate receptor subunit NR2C.
AB  - The murine N-methyl D-aspartate receptor subunit NR2C (epsilon-3) is encoded by a
      unique gene composed of 12 translated and three 5'-untranslated exons that spread
      over approximately 20 kilobases of genomic sequence. The GC-rich promoter that
      lacks TATA- and CAAT-positioning elements has two transcriptional start sites
      separated by 18 base pairs. One of these sites is located in a conserved
      initiator motif and, together with the first four exons, specifies the 5'
      untranslated sequence of 772 nucleotides. In this sequence, two alternative
      splice variants were detected that show identical expression patterns in adult
      mouse brain. Comparison of intron positions in genes encoding different members
      of the glutamate receptor family confirms a close evolutionary relationship of
      the NR2C and NMDAR1 subunit genes.

PMID- 7814403
TI  - M-CAT, CArG, and Sp1 elements are required for alpha 1-adrenergic induction of
      the skeletal alpha-actin promoter during cardiac myocyte hypertrophy.
      Transcriptional enhancer factor-1 and protein kinase C as conserved transducers
      of the fetal program in cardiac growth.
AB  - Induction of the fetal isogenes skeletal alpha-actin (skACT) and beta-myosin
      heavy chain (beta-MHC) is characteristic of cardiac growth in many models,
      suggesting a conserved signaling pathway. However, divergent regulation has also
      been observed. beta-Protein kinase C (PKC) and transcriptional enhancer factor-1
      (TEF-1) are involved in induction of beta-MHC in alpha 1-adrenergic-stimulated
      hypertrophy of cultured cardiac myocytes (Kariya, K., Farrance, I.K. G., and
      Simpson, P.C. (1993) J. Biol. Chem. 268, 26658-26662; Kariya, K., Karns, L. R.,
      and Simpson, P.C. (1994) J. Biol. Chem. 269, 3775-3782). In the present study, we
      asked whether the skACT promoter used the same mechanism. A mouse skACT promoter
      fragment (-113/-46) was induced by both alpha 1-adrenergic stimulation and co
      transfection of activated beta-PKC, and contained three required DNA sequence
      elements: M-CAT, CArG, and Sp1. The skACT M-CAT element bound TEF-1 in cardiac
      myocytes. Thus the skACT and beta-MHC promoters both require a TEF-1 binding site
      for activation by alpha 1-adrenergic stimulation, but differ in that skACT also
      requires a CArG box. These results provide a potential molecular basis for
      divergent regulation of the fetal program, and also imply that PKC and TEF-1 are
      conserved transducers for this program during cardiac growth.

PMID- 7814404
TI  - Structural and functional analysis of the promoter of the human alpha 1(XI)
      collagen gene.
AB  - In order to eventually elucidate the mechanisms regulating alpha 1(XI) collagen
      expression in cartilaginous and non-cartilaginous tissues, we performed an
      initial analysis of the structural-functional features of the promoter of the
      human gene (COL11A1). After cloning and sequencing the 5' portion of COL11A1,
      primer extension and nuclease protection assays identified several minor
      transcriptional start sites clustered around a major one located 318 base pairs
      from the ATG codon. Consistent with this finding, analysis of the upstream
      sequence revealed the absence of a TATA motif and the presence of several GC
      boxes. Transient transfection experiments delineated the smallest promoter
      sequence directing relatively high expression of a reporter gene in a cell type
      specific manner. Nine nuclear protein-bound areas were located within this
      promoter sequence of the COL11A1 gene. Sequence homologies suggested that the
      majority of the footprints correspond to potential binding sites for ubiquitous
      nuclear proteins, such as AP2 and Sp1. Additional experimental evidence indicated
      that one of the protected areas may bind a transcriptional complex that is
      identical or closely related to the one that regulates tissue specificity in the
      coordinately expressed alpha 2(V) collagen gene.

PMID- 7814405
TI  - Dominant negative mutations of the guanylyl cyclase-A receptor. Extracellular
      domain deletion and catalytic domain point mutations.
AB  - Guanylyl cyclase-A (GC-A), a receptor for A-type natriuretic peptide (ANP),
      contains an extracellular ligand-binding domain, a single transmembrane domain,
      and intracellular protein kinase-like and cyclase catalytic domains. Expression
      of the putative cyclase catalytic region (HCAT) resulted in the formation of an
      active enzyme that migrated as a homodimer on gel filtration columns; treatment
      with sodium trichloroacetate caused dissociation of the dimer and a loss of
      cyclase activity. Co-transfection of HCAT and full-length GC-A led to elevated
      basal intact cell cGMP concentrations and increased cell homogenate guanylyl
      cyclase activity. However, atrial natriuretic peptide-induced elevations of cGMP
      and cyclase activity were inhibited by the introduction of HCAT. Alanine scanning
      mutagenesis of highly conserved residues within HCAT identified one mutation
      (D893A) that destroyed enzyme activity but not the ability of the mutant subunit
      to form homodimers. The mutant subunit inhibited the cyclase activity of wild
      type HCAT (approximately 70%) as well as that of full-length GC-A (approximately
      85%) in co-expression studies where the amount of wild-type HCAT or full-length
      GC-A was not altered. Unlike co-transfection with wild-type HCAT, co-transfection
      of HCA-TD893A and GC-A did not result in elevated basal intact cell cGMP
      concentrations. For the first time we describe deletion and point mutations
      within the plasma membrane family of guanylyl cyclase receptors that result in
      the formation of effective dominant negative proteins.

PMID- 7814406
TI  - Isolation and molecular cloning of a novel bone phosphoprotein related in
      sequence to the cystatin family of thiol protease inhibitors.
AB  - We describe here the isolation of a novel non-collagenous protein from the acid
      demineralization extract of bovine cortical bone. This 24-kDa protein is multiply
      phosphorylated at serine residues in Ser-X-Glu/Ser(P) sequences, a recognition
      motif for phosphorylation by the secretory pathway protein kinase, and we have
      termed this protein secreted phosphoprotein 24 (spp24). The cDNA structure of
      spp24 was determined by sequencing cDNA fragments obtained by reverse
      transcription-polymerase chain reaction, 3'-rapid amplification of cDNA ends, and
      screening a lambda gt11 cDNA library. This cDNA sequence predicts a 200-residue
      initial translation product which consists of a 20-residue signal sequence and
      the 180-residue mature spp24. Northern blot analysis using the spp24 cDNA showed
      that spp24 mRNA is in liver and bone but not in heart, lung, kidney, or spleen. A
      search of existing protein sequences revealed that the N-terminal 107 residues of
      mature spp24 are related in sequence to the cystatin family of thiol protease
      inhibitors, which suggests that spp24 could function to modulate the thiol
      protease activities that are known to be involved in bone turnover. Several of
      the proteins in the cystatin family that are most closely related to spp24 are
      not only thiol protease inhibitors but are also precursors to peptides with
      potent biological activity, peptides such as bradykinin and the neutrophil
      antibiotic peptides. It is therefore possible that the intact form of spp24 found
      in bone could also be a precursor to a biologically active peptide, a peptide
      which could coordinate an aspect of bone turnover.

PMID- 7814407
TI  - Riboflavin biosynthesis in Saccharomyces cerevisiae. Cloning, characterization,
      and expression of the RIB5 gene encoding riboflavin synthase.
AB  - Saccharomyces cerevisiae has a monofunctional riboflavin synthase that catalyzes
      the formation of riboflavin from 6,7-dimethyl-8-ribityllumazine. We have isolated
      the gene encoding this enzyme from a yeast genomic library by functional
      complementation of a mutant, rib5-10, lacking riboflavin synthase activity.
      Deletion of the chromosomal copy of RIB5 led to riboflavin auxotrophy and loss of
      enzyme activity. Intragenic complementation between point and deletion mutant
      alleles suggested that the encoded protein (Rib5p) assembles into a multimeric
      complex and predicted the existence of a discrete functional domain located at
      the N terminus. Nucleotide sequencing revealed a 714-base pair open reading frame
      encoding a 25-kDa protein. Rib5p was purified to apparent homogeneity by a simple
      procedure. The specific activity of the enzyme was enriched 8500-fold. The N
      terminal sequence of the purified enzyme was identical to the sequence predicted
      from the nucleotide sequence of the RIB5 gene. Initial structural
      characterization of riboflavin synthase by gel filtration chromatography and both
      nondenaturing pore limit and SDS-polyacrylamide gel electrophoresis showed that
      the enzyme forms a trimer of identical 25-kDa subunits. The derived amino acid
      sequence of RIB5 shows extensive homology to the sequences of the alpha subunits
      of riboflavin synthase from Bacillus subtilis and other prokaryotes. In addition,
      the sequence also shows internal homology between the N-terminal and the C
      terminal halves of the protein. Taken together, these results suggest that the
      Rib5p subunit contains two structurally related (substrate-binding) but
      catalytically different (acceptor and donator) domains.

PMID- 7814409
TI  - Gain-of-function mutations conferring actin-severing activity to human macrophage
      cap G.
AB  - Nonmuscle cell motility requires marked changes in the consistency and shape of
      the peripheral cytoplasm. These changes are regulated by a gel-sol transformation
      of the actin filament network, and actin filament-severing proteins are
      responsible for network solation. Macrophage Cap G, unlike all other proteins in
      the gelsolin family, caps but does not sever actin filaments. Two amino acid
      stretches in Cap G diverge markedly from the severing proteins: 84LNTLLGE and
      124AFHKTS. Discrete mutations in Cap G have been generated to determine if these
      amino acid sequences are critical for actin filament severing. Conversion of
      84LNTLLGE to the gelsolin actin-binding helix sequence (84LDDYLGG) renders Cap G
      capable of severing actin filaments (half-maximal severing, 1-2 microM). Adding a
      second set of mutations, converting 124AFHKTS to 124GFKHV, enhances severing by
      10-fold (half-maximal severing, 0.1-0.2 microM). These experiments support a
      critical role for these two regions in actin filament severing and showcase the
      power of gain-of-function mutations in clarifying structure-function
      relationships.

PMID- 7814408
TI  - Inhibition of macrophage Ca(2+)-independent phospholipase A2 by bromoenol lactone
      and trifluoromethyl ketones.
AB  - A novel Ca(2+)-independent phospholipase A2 (PLA2) has recently been purified
      from the murine macrophage-like cell line P388D1 (Ackermann, E. J., Kempner, E.
      S., and Dennis, E. A. (1994) J. Biol. Chem. 269, 9227-9233). This enzyme is now
      shown to be inhibited by palmitoyl trifluoromethyl ketone (PACOCF3), arachidonyl
      trifluoromethyl ketone (AACOCF3), and a bromoenol lactone (BEL). Both PACOCF3 and
      AACOCF3 were found to inhibit the macrophage PLA2 in a concentration-dependent
      manner. PACOCF3 was found to be approximately 4-fold more potent than AACOCF3,
      with IC50 values of 3.8 microM (0.0075 mol fraction) and 15 microM (0.028 mol
      fraction), respectively. Reaction progress curves in the presence of either
      inhibitor were found to be linear, and the PACOCF3.PLA2 complex rapidly
      dissociated upon dilution. BEL was also found to inhibit the macrophage PLA2 in a
      concentration-dependent manner, with half-maximal inhibition observed at 60 nM
      after a 5-min preincubation at 40 degrees C. Inhibition was not reversed after
      extensive dilution of the enzyme into assay buffer. Treatment of the PLA2 with
      BEL resulted in a linear, time-dependent inactivation of activity, and the rate
      of this inactivation was diminished in the presence of PACOCF3. In addition, PLA2
      treated with [3H]BEL resulted in the covalent labeling of a major band at M(r)
      80,000. Inactivation of the PLA2 by 5,5'-dithiobis(2-nitrobenzoic acid) prior to
      treatment with [3H]BEL resulted in the near complete lack of labeling consistent
      with covalent irreversible suicide inhibition of the enzyme. The labeling of a
      M(r) 80,000 band rather than a M(r) 40,000 band upon treatment with [3H]BEL
      distinguishes the macrophage Ca(2+)-independent PLA2 from a previously identified
      myocardial Ca(2+)-independent PLA2 and provides strong evidence that the M(r)
      80,000 protein is the catalytic subunit.

PMID- 7814410
TI  - Intramuscular delivery of rat kallikrein-binding protein gene reverses
      hypotension in transgenic mice expressing human tissue kallikrein.
AB  - The tissue kallikrein-kinin system has been postulated to play a role in blood
      pressure regulation. The activity of tissue kallikrein is controlled by a number
      of factors in vivo. Rat kallikrein-binding protein (RKBP) is a serine proteinase
      inhibitor which binds to and inhibits tissue kallikrein's activity in vitro. We
      have recently developed several hypotensive transgenic mouse lines which express
      human tissue kallikrein. In order to investigate the role of RKBP in blood
      pressure regulation, we delivered the RKBP to these transgenic mice by
      intramuscular injection. Expression of the RKBP was detected in skeletal muscle
      by reverse transcription-polymerase chain reaction and Southern blot analysis at
      10, 20, 30, and 40 days post-injection. Immunoreactive RKBP levels in the muscle
      and serum of these mice were quantified by a RKBP-specific enzyme-linked
      immunosorbent assay and Western blot analysis. The levels of RKBP mRNA and
      immunoreactive protein were detectable at 10 days post-injection and increased
      significantly at 20 and 30 days. During this period, RKBP delivery significantly
      increased systemic blood pressure in the kallikrein transgenic mice to a level
      comparable to that of normotensive control mice. The RKBP and vector DNA delivery
      had no effect on the blood pressure of normotensive control mice. No serum
      antibodies to RKBP or its DNA were detected in the mice 40 days post injection.
      These results suggest that the increase of systemic blood pressure by RKBP
      delivery in these hypotensive transgenic mice may be mediated by inhibiting
      tissue kallikrein activity.

PMID- 7814411
TI  - Identification in the calcineurin A subunit of the domain that binds the
      regulatory B subunit.
AB  - Calcineurin (CaN) is the serine/threonine protein phosphatase (phosphatase 2B)
      that is activated by binding of Ca2+ to its B subunit and to calmodulin (CaM).
      This paper identifies residues between the catalytic region and the CaM-binding
      domain of the A subunit as the domain that binds the regulatory B subunit. A
      purified fusion protein containing residues 328-390 of the A subunit 1) binds CaN
      B subunit, and 2) inhibits (IC50 = 0.1 microM) the in vitro stimulation of CaN A
      phosphatase activity by purified CaN B subunit. A synthetic peptide corresponding
      to residues 341-360 blocked the binding of CaN B to residues 328-390 in the
      fusion protein, so 4 hydrophobic residues within this region (Val349-Phe350 and
      Phe356-Val357) were mutated to either Glu (E mutant) or Gln (Q mutant). The wild
      type and mutant A subunits were expressed individually or coexpressed with B
      subunit in Sf9 cells, purified and characterized. The mutant A subunits were
      similar to wild-type A subunit in terms of basal phosphatase activity (1-3
      nmol/min/mg) and activation by Mn2+/CaM. Addition of purified B subunit to
      purified wild-type A subunit at a 1:1 molar ratio gave a 40-fold increase in
      phosphatase activity whereas addition of B subunit to either of the mutant A
      subunits had no effect on phosphatase activity, even at a 3:1 molar excess of B
      subunit. Furthermore, when wild-type or mutant A subunits were coexpressed with B
      subunit and purified on CaM-Sepharose, the B subunit co-eluted with the wild-type
      A subunit but not with either mutant A subunit. These results demonstrate that
      residues 328-390 in the A subunit bind B subunit and that the mutated hydrophobic
      residues are essential.

PMID- 7814412
TI  - Molecular cloning of the mature NAD(+)-dependent succinic semialdehyde
      dehydrogenase from rat and human. cDNA isolation, evolutionary homology, and
      tissue expression.
AB  - Three rat brain cDNA clones approximately 3500, 1465, and 1135 base pairs in
      length encoding succinic semialdehyde dehydrogenase (SSADH; EC 1.2.1.24) were
      isolated from two cDNA libraries using a polymerase chain reaction derived probe.
      Restriction mapping and DNA sequencing revealed that the 3.5-kilobase clone
      contained an 84-base pair (28 amino acid) insert in the coding region. Composite
      clones encoding mature SSADH predicted proteins with 488 amino acids (M(r) =
      52,188) when including the insert and 460 amino acids (M(r) = 48,854) without the
      insert. The cDNA clones were confirmed by expression of enzyme activity in
      bacteria and protein sequence data obtained from sequencing purified rat brain
      SSADH. Two human liver SSADH cDNA clones of 1091 and 899 base pairs were also
      isolated. Human and rat SSADH share 83 and 91% identity in nucleotide and protein
      sequence, respectively. Northern blot analysis revealed two differentially
      expressed SSADH transcripts of approximately 2.0 and 6.0 kilobases in both rat
      and human tissues. Human genomic Southern blots indicate that the two SSADH
      transcripts are encoded by a greater than 20-kilobase single copy gene. Mammalian
      SSADH contains significant homology to bacterial NADP(+)-succinic semialdehyde
      dehydrogenase (EC 1.2.1.16) and conserved regions of general aldehyde
      dehydrogenases (EC 1.2.1.3), suggesting it is a member of the aldehyde
      dehydrogenase superfamily of proteins.

PMID- 7814413
TI  - Studies on transcription activation by the multimeric CCAAT-binding factor CBF.
AB  - The CCAAT-binding factor CBF is a heteromeric transcription factor that
      specifically binds to CCAAT sequences in many eukaryotic genes. CBF consists of
      three subunits, CBF-A, CBF-B, and CBF-C, all three of which are necessary for DNA
      binding. In this study we examined the transcription activation function of CBF
      by two different approaches. We first used a heterologous system in which a
      series of deletion mutations of CBF-B, fused to the bacterial LexA DNA binding
      domain, were transfected into HeLa cells together with a reporter gene driven by
      a minimal promoter containing LexA binding sites. These experiments showed that
      CBF-B needed both a glutamine-rich domain and an adjacent serine/threonine-rich
      domain to activate the reporter gene optimally. The glutamine-rich domain by
      itself activated transcription only modestly. We also set up an in vitro
      transcription reconstituted system in which trans-activation by CBF occurred
      through a physiological CCAAT motif. Nuclear extracts from NIH 3T3 cells were
      first depleted of CBF and then complemented with recombinant CBF-B and a highly
      purified fraction containing native CBF-A and CBF-C. Recombinant full-length CBF
      B together with CBF-A and CBF-C activated transcription of several alpha 2(I)
      collagen gene promoter constructs. We then tested whether in this system the
      glutamine- and serine/threonine-rich domains of CBF-B were needed for trans
      activation by CBF. We generated a truncated form of CBF-B that was still able to
      bind DNA in the presence of CBF-A and CBF-C. Even in the absence of the glutamine
      and serine/threonine-rich domains of CBF-B, reconstituted CBF did activate
      transcription, suggesting that CBF transcriptional activation can also be
      mediated by the other subunits of CBF or by another transcription factor present
      in the nuclear extracts that interacts with CBF. Taken together our results
      suggest a model in which CBF has the potential to activate transcription either
      through the glutamine- and serine/threonine-rich domains of CBF-B or through the
      other subunits of CBF or through another component recruited by CBF.

PMID- 7814414
TI  - Deletion of lysine 121 creates a temperature-sensitive alteration in insulin
      binding by the insulin receptor.
AB  - Recently we reported the deletion of Lys-121 in one allele of the insulin
      receptor gene from a child with severe insulin resistance. In the present work,
      this mutant receptor (M121) was shown to have an abnormal sensitivity to
      temperature and an alteration in "negative cooperativity." In contrast to the
      wild-type receptor (HIRC), insulin binding by the M121 receptor was rapidly and
      irreversibly lost at temperatures above 30 degrees C with the phosphorylated form
      of the receptor being more temperature-sensitive than the nonphosphorylated form.
      Although insulin binding activity was lost, Western analysis and other studies
      showed that the mutant receptor remained intact. Measurements of 125I-insulin
      dissociation at 21 degrees C in the presence of native insulin (an estimate of
      negative cooperativity) demonstrated a difference between the mutant and wild
      type receptor. Insulin dissociation from the mutant receptor was not as
      pronounced as that found with the wild-type receptor. Thus, an abnormality in
      insulin binding by the mutation was evident at lower "permissive" temperatures.
      The results of these and other studies argue that Lys-121 occupies an important
      position for the regulation of insulin receptor conformation. This regulation
      apparently influences negative cooperative interactions with insulin and
      modulates signal transduction.

PMID- 7814415
TI  - Cloning and expression of a novel truncated calcium channel from non-excitable
      cells.
AB  - Calcium entry, via a dihydropyridine-sensitive pathway, is required for
      differentiation in murine erythroleukemia cells (MELC). Calcium channel currents
      have been identified physiologically in some non-excitable cells, but little is
      known regarding the structure of these channels. We show that a truncated form of
      the alpha 1 subunit of the cardiac voltage-gated calcium channel (dihydropyridine
      receptor, DHPR) is expressed in MELC. This MELC calcium channel lacks the first
      four transmembrane segments of the DHPR (IS1 to IS4). A MELC calcium
      channel/cardiac DHPR chimera, co-expressed with the alpha 2 and beta subunits of
      the DHPR, forms a functional calcium channel in Xenopus oocytes.

PMID- 7814416
TI  - A neuronal protein tyrosine phosphatase induced by nerve growth factor.
AB  - A new protein tyrosine phosphatase (PC12-PTP1) was identified in nerve growth
      factor (NGF)-treated PC12 cells. The mRNA level of PC12-PTP1 is increased 9-fold
      over the initial 8 h of NGF treatment and then decreases dramatically after 24 h
      of treatment. In rat brain, three transcripts corresponding to 1.5, 2.6, and 3.0
      kilobases (kb) in size are detected by Northern blot analysis. Although the 1.5-
      and 2.6-kb transcripts are present in brain and other tissues, the 3-kb
      transcript is exclusively expressed in brain and the expression of this
      transcript alone increases following NGF treatment. PC12-PTP1 is a non-receptor
      protein tyrosine phosphatase (PTP) with a 50% sequence homology in the
      phosphatase domain with several other non-receptor PTPs. PC12-PTP1 fusion protein
      exhibits tyrosine phosphatase activity, and in vitro translation of the PC12-PTP1
      transcript produces a major protein of 39 kDa. The data presented suggest that
      NGF regulates the expression of PC12-PTP1 during periods of neuronal growth and
      differentiation.

PMID- 7814418
TI  - Production and oxidation of indole by Haemophilus influenzae.
AB  - During growth in high concentrations of iron nitrate, H. influenzae produces
      compounds reactive in biochemical assays for hydroxamates. Mixing experiments
      established that nitrate was responsible for inducing these compounds. Analysis
      by 1H and 13C NMR and high resolution mass spectrometry identified the active
      species as 2,2-bis(3'-indolyl)indoxyl. Bacterial production of the latter
      compound has been previously observed only in Pseudomonas aureofaciens. A mutant
      defective in the production of 2,2-bis(3'-indolyl)indoxyl was constructed by
      marker insertion. The formation of indole and 2,2-bis (3'-indolyl)indoxyl was
      quantitated by reverse-phase high pressure liquid chromatography during growth in
      high concentrations of nitrate. The mutant produced high concentrations of
      indole, but only minimal amounts of 2,2-bis(3'-indolyl)indoxyl, and also proved
      to be defective in nitrate reduction. These data suggest that indole may function
      as an electron donor for nitrate reductase in H. influenzae.

PMID- 7814417
TI  - Requirement of tyrosine- and serine/threonine kinases in the transcriptional
      activation of the mammalian grp78/BiP promoter by thapsigargin.
AB  - Depletion of endoplasmic reticulum (ER) Ca2+ store by thapsigargin (Tg) in
      mammalian cells induces a set of ER protein genes known as the glucose-regulated
      proteins. Recently, IRE1p, a transmembrane protein postulated to have a
      serine/threonine kinase activity, has been identified as required for the
      induction of ER resident proteins genes in Saccharomyces cerevisiae. To
      investigate whether IRE1p can stimulate mammalian grp transcription, a stable
      Chinese hamster ovary cell line containing amplified copies of IRE1p has been
      created. The IRE1p expressing transfectants exhibited a modest (2-fold)
      enhancement of both the basal and Tg induced level of grp78 and grp94, two
      coordinately regulated grp genes. Using okadaic acid as a specific inhibitor for
      the endogenous serine/threonine protein phosphatase activities, a mild (2-fold)
      stimulative effect was observed for Tg induction of grp78 transcription. The
      okadaic acid potentiating effect requires a 50-base pair region in the vicinity
      of the grp78 TATA element. In contrast, the transcriptional activation of grp78
      by Tg is almost totally eliminated by genistein, a tyrosine kinase inhibitor. The
      grp core, the C3 and C1 elements which are major Tg response elements of the rat
      grp78 promoter, are also major targets of the inhibitive effects of genistein.

PMID- 7814419
TI  - Glycine 122 is essential for cooperativity and binding of Mg2+ to porcine
      fructose-1,6-bisphosphatase.
AB  - Site-directed mutagenesis of an amino acid residue in the substrate binding site
      of porcine fructose-1,6-bisphosphatase was carried out based on the crystal
      structure of the enzyme (Zhang, Y., Liang, J.-Y., Huang, S., Ke, H., and
      Lipscomb, W. N. (1993) Biochemistry 32, 1844-1857). A mutant enzyme form of
      fructose-1,6-bisphosphatase, G122A, was purified and characterized by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis, circular dichroism
      spectrometry (CD), and initial rate kinetics. There were no discernible
      differences between the secondary structures of the wild-type and the mutant
      enzyme on the basis of CD data. Altering Gly-122 to alanine caused a significant
      decrease in the enzyme's activity and affinity for Mg2+. The kcat for this mutant
      enzyme was only about 5% of that of wild-type fructose-1,6-bisphosphatase, and
      the Ka for Mg2+ was about 20-fold higher than that of the wild-type enzyme. The
      Ki for AMP was increased 77-fold in the case of the mutant enzyme; however, the
      Hill coefficient was unaltered. Most importantly, it was observed that
      replacement of Gly-122 with alanine caused the total loss of cooperativity for
      Mg2+. It is concluded that Gly-122 is essential for Mg2+ cooperativity and
      important for binding of Mg2+ and AMP as well as for enzyme activity.

PMID- 7814420
TI  - Dynamics of signaling during insulin-stimulated endocytosis of its receptor in
      adipocytes.
AB  - Insulin causes rapid insulin receptor autophosphorylation, receptor endocytosis,
      and phosphorylation of its principle substrate (IRS-1). Using rat adipocytes, we
      studied the dynamics of receptor autophosphorylation, the kinase activity, and
      the IRS-1 phosphorylation state relative to the subcellular localization of these
      proteins. After 2 min of insulin exposure, the specific phosphotyrosine content
      of the insulin receptor in the internal membranes (IM) peaks at a level 5-6-fold
      higher than the plasma membrane (PM) receptor and then declines after 5-8 min to
      a level similar to the PM receptor. The exogenous kinase activity of these
      receptors exactly mirrored their phosphotyrosine content. The distribution of IRS
      1 is 80% cytosolic, 20% IM-associated, and essentially undetectable in the PM.
      The phosphorylation state of IRS-1 in the IM parallels that of the insulin
      receptor, but cytosolic IRS-1 phosphorylation remains constant. Insulin-dependent
      GLUT4 translocation to the PM occurs after the peak of IRS-1 phosphorylation. The
      data are consistent with the hypothesis that insulin action may be mediated by
      receptor internalization and interaction with its substrate(s) associated with
      internal membranes. A small fraction of phosphorylated insulin receptors is
      sufficient for signal transduction. The dephosphorylation of the insulin receptor
      and IRS-1 in the IM appears to be a concerted process, possibly mediated by the
      same enzyme.

PMID- 7814421
TI  - Hepsin, a putative membrane-associated serine protease, activates human factor
      VII and initiates a pathway of blood coagulation on the cell surface leading to
      thrombin formation.
AB  - Previous studies have shown that hepsin is a putative membrane-associated serine
      protease that is required for cell growth (Torres-Rosado, A., O'Shea, K. S.,
      Tsuji, A., Chou, S.-H., and Kurachi, K. (1993) Proc. Natl. Acad. Sci. U.S. A. 90,
      7181 7185). In the present study, we have transfected baby hamster kidney (BHK)
      cells with a plasmid containing the cDNA for human hepsin and examined these
      cells for their ability to activate several blood coagulation factors including
      factors X, IX, VII, prothrombin, and protein C. Little, if any, proteolytic
      activation of factors X, IX, prothrombin, or protein C was observed when these
      clotting factors were incubated with hepsin-transfected cells. On the other hand,
      hepsin-transfected cells proteolytically activated significant concentrations of
      human factor VII in a time- and calcium-dependent manner, whereas essentially no
      activation of factor VII was observed in BHK cells transfected with plasmid
      lacking the cDNA for hepsin. The factor VII activating activity in the hepsin
      transfected BHK cell line was confined exclusively to the total membrane fraction
      and was inhibited > 95% by antibody raised against a fusion protein consisting of
      maltose-binding protein and the extracellular domain of human hepsin. An active
      site factor VII mutant, S344A factor VII, was cleaved as readily as plasma
      derived factor VII by hepsin-transfected cells, indicating that factor VII was
      not converted to factor VIIa autocatalytically on the cell surface. In contrast,
      an activation cleavage site factor VII mutant, R152E factor VII, was not cleaved
      by hepsin-transfected cells, suggesting that factor VII and S344A factor VII were
      activated on these cells by cleavage of the Arg152-Ile153 peptide bond. In the
      copresence of factor VII and factor X, hepsin-transfected BHK cells supported the
      formation of factor Xa. In addition, in the copresence of factor VII, factor X,
      and prothrombin, hepsin-transfected BHK cells supported the formation of
      thrombin. These results strongly suggest that membrane-associated hepsin converts
      zymogen factor VII to factor VIIa, which in turn, is capable of initiating a
      coagulation pathway on the cell surface that ultimately leads to thrombin
      formation.

PMID- 7814422
TI  - On the structure of bilirubin in solution. 13C[1H] heteronuclear Overhauser
      effect NMR analyses in aqueous buffer and organic solvents.
AB  - Select hydrogen-carbon distances have been determined from 13C[1H] heteronuclear
      Overhauser effects observed in a 99% carbon-13 enriched 13CO2H bilirubin analog,
      [8(3), 12(3)-13C2]-mesobilirubin XIII alpha. Analysis of the data confirms that
      the propionic acid carbonyl lies within hydrogen bonding distance to the
      dipyrrinone lactam and pyrrole N-H groups in chloroform and indicates,
      surprisingly, that those distances are only slightly longer in dimethyl sulfoxide
      solvent or when the carboxyl group is ionized in pH 7.4 aqueous buffered
      solutions of the pigment. The data supports the presence and persistence of
      folded, intramolecularly hydrogen-bonded bilirubin conformations in solution.

PMID- 7814423
TI  - Two closely related isoforms of protein kinase C produce reciprocal effects on
      the growth of rat fibroblasts. Possible molecular mechanisms.
AB  - We have previously reported that two closely related protein kinase C (PKC)
      isoforms, PKC alpha and PKC beta I, had divergent effects on the growth and
      transformation of the same parental R6 rat embryo fibroblast cell line (Housey,
      G. M., Johnson, M. D., Hsiao, W.-L. W. O'Brian, C. A., Murphey, J. P.,
      Kirschmeier, P., and Weinstein, I. B. (1988) Cell 52, 343-354; Borner, C.,
      Filipuzzi, I., Weinstein, I. B., and Imber, R. (1991) Nature 353, 78-80). Whereas
      cells that overexpress PKC beta I lost anchorage dependence, grew to higher
      saturation densities, and generated small tumors when injected into nude mice,
      none of these properties were seen with cells that overexpress PKC alpha. In
      fact, the latter cells grew even slower and to lower saturation densities as
      compared to control cells. Here we investigate possible molecular mechanisms
      underlying the reciprocal effects of PKC alpha and PKC beta I. Overexpression of
      both isoforms enhanced 12-O-tetradecanoyl phorbol-13 acetate-induced expression
      of the growth regulatory genes c-jun, c-myc, and collagenase and enhanced
      feedback inhibition of epidermal growth factor receptor binding and cellular
      levels of diacylglycerol. However, the cells overexpressing PKC beta I differed
      from those overexpressing PKC alpha by displaying a decreased requirement for
      growth factors and by the production of a mitogenic factor. Thus, the basis for
      enhanced growth and transformation of cells overexpressing PKC beta I may be the
      establishment of an autocrine growth factor loop. These findings may be relevant
      to the roles of specific isoforms of PKC in carcinogenesis and tumor growth.

PMID- 7814424
TI  - Changing the ion binding specificity of the Escherichia coli H(+)-transporting
      ATP synthase by directed mutagenesis of subunit c.
AB  - Most F1F0 type ATP synthases, including that in Escherichia coli, use H+ as the
      coupling ion for ATP synthesis. However, the structurally related F1F0 ATP
      synthase in Propionigenium modestum uses Na+ instead. The binding site for Na+
      residues in the F0 sector of the P. modestum enzyme. We postulated that Na+ might
      interact with subunit c of F0. Subunit c of P. modestum and E. coli are
      reasonably homologous (19% identity) but show striking variations around the H(+)
      translocating, dicyclohexylcarbodiimide-reactive carboxyl (Asp61 in E. coli).
      Several hydrophobic residues around Asp61 were replaced with polar residues
      according to the P. modestum sequence in the hope that the polar replacements
      might provide liganding groups for Na+. One mutant from 31 different mutation
      combinations did generate an active enzyme that binds Li+, the combination being
      V60A, D61E, A62S, and I63T. Li+ binding was detected by Li+ inhibition of ATP
      driven H+ transport, Li+ inhibition of F1F0-ATPase activity, and Li+ inhibition
      of F0-mediated H+ transport. The Li+ effects were observed with membrane vesicles
      prepared from a delta nhaA, delta nhaB mutant background which lacks Na+/H+
      antiporters, and with purified, reconstituted preparations of F0 prepared from
      this background strain. Li+ inhibition was observed at pH 8.5 but not at pH 7.0.
      H+ thus appears to compete with Li+ for the binding site. Li+ binding was
      abolished by replacement of Glu61 by Asp or Ser62 by Ala. The side chains at
      Ala60 and Thr63 may act in a supporting structural role by providing a more
      flexible conformation for the Li+ binding cavity. Thr63 does not appear to
      provide a liganding group since H+ transport in two other mutants, with Gly or
      Ala in place of Thr63, was also inhibited by Li+. We suggest that a X-Glu-Ser-Y
      or X-Glu-Thr-Y sequence may provide a general structural motif for monovalent
      cation binding, and that the flexibility provided by residues X and Y will prove
      crucial to this structure.

PMID- 7814426
TI  - Beta 2 (CD18) mutations abolish ligand recognition by I domain integrins LFA-1
      (alpha L beta 2, CD11a/CD18) and MAC-1 (alpha M beta 2, CD11b/CD18).
AB  - The "I" domains of the beta 2 (CD18) leukocyte integrins are implicated in ligand
      binding function. Moreover, rather than recognizing linear peptide sequences,
      this class of integrins generally recognizes multiple discontinuous sites on
      immunoglobulin superfamily adhesion receptors. A conserved cluster of oxygenated
      residues is involved in ligand recognition by beta 1 and beta 3 integrins. In the
      present study, we evaluated the role of this region in the I domain-containing
      beta 2 integrins. Recombinant alpha L beta 2 (LFA-1, CD11a/CD18) and alpha M beta
      2 (MAC-1, CD11b/CD18) were expressed on COS cells, and function was assessed by
      adhesion to ICAM-1 or iC3b, respectively. Alanine substitution at position Asp134
      or Ser136 in beta 2 produced a complete loss in the capacity of both alpha L beta
      2 and alpha M beta 2 to support cell adhesion. In contrast, substitution at
      Asp128 or Ser138 resulted in loss of beta 2 surface expression when co
      transfected with alpha L (CD11a) or alpha M (CD11b). These data provide the first
      evidence for involvement of the beta 2 subunit in ligand binding to I domain
      integrins.

PMID- 7814425
TI  - Proteolytic processing of NF-kappa B/I kappa B in human monocytes. ATP-dependent
      induction by pro-inflammatory mediators.
AB  - Proteolytic processing of select constituents of the nuclear factor kappa B (NF
      kappa B)/inhibitor kappa B alpha (I kappa B) transcription factor system plays an
      important role in regulating the biological responses of monocytes to pro
      inflammatory mediators. Nuclear translocation of NF-kappa B is preceded by the
      proteolytic degradation of I kappa B alpha, an ankyrin motif-rich inhibitor that
      traps NF-kappa B in the cytoplasm. In addition, formation of cytoplasmic NF-kappa
      B/I kappa B alpha complexes in quiescent cells requires constitutive proteolytic
      processing of p105, another ankyrin motif-rich inhibitory protein from which the
      p50 subunit of NF-kappa B is generated. We have demonstrated that, following
      stimulation of human monocytic cells with lipopolysaccharide or tumor necrosis
      factor-alpha, this critical p105 processing event is up-regulated in concert with
      the inactivation of I kappa B alpha. Moreover, the degradative loss of both p105
      and I kappa B alpha is prevented in cells depleted of intracellular ATP. In
      activated monocytes, however, I kappa B alpha degradation occurs more rapidly
      than p105 processing to p50. Together these findings provide direct biochemical
      evidence that p105 and I kappa B alpha are differentially sensitive targets for
      inducible proteolysis via ATP-dependent degradative pathways.

PMID- 7814427
TI  - A molecular genetic approach for the identification of essential residues in
      human glutathione S-transferase function in Escherichia coli.
AB  - The common substrate for glutathione S-transferases (GSTs), 1-chloro-2,4
      dinitrobenzene (CDNB), is an inhibitor of Escherichia coli growth. This growth
      inhibition by CDNB is enhanced when E. coli expresses a functional GST. Cells
      under growth inhibition have reduced intracellular GSH levels and form filaments
      when they resume growth. Based on this differential growth inhibition by CDNB we
      have developed a simple procedure to select for null-mutants of a human GST in E.
      coli. Null mutations in the human GST gene from hydroxylamine mutagenesis or
      oligonucleotide-directed mutagenesis can be selected for on agar plates
      containing CDNB after transformation. The molecular nature of each mutation can
      be identified by DNA sequence analysis of the mutant GST gene. We have identified
      three essential amino acid residues in an alpha class human GST at Glu31, Glu96,
      and Gly97. Single substitution at each of these residues, E31K, E96K, G97D,
      resulted in mutant GST proteins with loss of CDNB conjugation activity and
      failure in binding to the S-hexyl GSH affinity matrix. In contrast, a mutant GST
      (Y8F) resulting from substitution of the conserved tyrosine near the N terminus
      has much reduced CDNB conjugation activity but was still capable of binding to
      the S-hexyl GSH-agarose. Additional mutant GSTs with substitutions at position 96
      (E96F, E96Y) and 97 (G97P, G97T, G97S) resulted in changes in both Km and kcat to
      different extents. The in vitro CDNB conjugation activity of the purified mutant
      enzymes correlate negatively with the plating efficiencies of strains encoding
      them in the presence of CDNB. Based on the x-ray structure model of human GST 1
      1, two of these residues are involved in salt bridges (Arg19-Glu31, Arg68-Glu96)
      and the third Gly97 is in the middle of the helix alpha 4. Our results provide
      evidence in vivo that Tyr8, Gly97, and the two salt bridges are important for GST
      structure-function. This molecular genetic approach for the identification of
      essential amino acids in GSTs should be applicable to any GSTs with CDNB
      conjugation activity. It should also complement the x-ray crystallographic
      approach in understanding the structure and function of GSTs.

PMID- 7814429
TI  - Chemical and physical properties of collagen implants influence their fate in
      vivo as evaluated by light and confocal microscopy.
AB  - Porcine collagen membranes having a rough and a smooth side were used for
      subcutaneous implantation studies in rats. Two tanning protocols were used for
      the membranes, a new one involving microwaving and glutaraldehyde treatment
      (NEWGA), and the other, a conventional method using glutaraldehyde treatment at
      room temperature (OLDGA). Untreated membranes (NONGA) were also implanted.
      Sections of the implants were examined by light microscopy and with the confocal
      laser scanning microscope focusing on neovascularization and incorporation of the
      implant. At 64 days, the smooth sides of NEWGA and OLDGA implants were not well
      incorporated, with scarring subjacent to the surface and dystrophic calcification
      of that side of the membrane. At the same time, the rough sides of the NEWGA and
      OLDGA were not calcified with a giant cell reaction around the porcine collagen.
      The best incorporation was found in the NONGA membranes with no dystrophic
      calcification, excellent neovascularization of all layers, and complete
      remodeling at day 64. After 5 months, the completely remodeled NONGA membrane
      still could be identified, and the NEWGA and OLDGA membranes were calcified with
      a giant cell reaction having a dense fibrous capsule. It is concluded that if
      cross-linking is deemed necessary, the microwave cross-linking method is
      advisable because in the early stages there is less reactive inflammation around
      it, and the implant surfaces should be rough with an open structure, making
      calcification of cross-linked collagen unlikely.

PMID- 7814428
TI  - Feasibility of agarose microbeads with xenogeneic islets as a bioartificial
      pancreas.
AB  - A bioartificial pancreas, that is, transplantation of islets of Langerhans
      (islets) which are enclosed in a semipermeable membrane, has been proposed as a
      treatment for type I diabetes. The islets are immuno-isolated from the host by
      the semipermeable membrane preventing rejection while maintaining control of
      glucose metabolism for an extended period. The purpose of the current research is
      to evaluate the feasibility of preparing agarose microbeads with xenogeneic
      hamster islets as a bioartificial pancreas in streptozotocin induced diabetic
      mice. In the recipients with a low level of anti-hamster antibodies, the
      combination of encapsulation of hamster islets in 5% agarose microbeads and in
      vitro culture of them prolonged xenograft survivals. Four of 6 recipients were
      still normoglycemic at 100 days after implantation. However, the same procedure
      was not effective in the recipients which were sensitized in advance by
      transplantation of free hamster islets and thus had high levels of anti-hamster
      antibodies. The average normoglycemic period was 32 days. Antibodies permeated
      through the microbeads and activated complement on the cell surfaces. The network
      of agarose microbeads was rendered dense by increasing the concentration of
      agarose to restrict the diffusion of antibodies. Graft survivals were prolonged
      with increasing concentrations of agarose. As an analysis using diffusion
      equations predicted, the survivals were inversely proportional to the diffusion
      coefficient of IgG in each agarose gel. Islet xenotransplantation was enabled by
      the combination of the microbeads with a concentration of agarose higher than
      7.5% and in vitro culture even in recipients having a high level of preformed
      antibodies.

PMID- 7814430
TI  - Bonding of low-fusing dental porcelain to commercially pure titanium.
AB  - The objective of the investigation was to study the basic problems related to the
      firing of dental porcelain to commercially pure titanium. The firing of a low
      fusing porcelain to sandblasted or electrolytically polished titanium was carried
      out in an ordinary dental furnace. The interfacial regions between the ceramic
      coatings and titanium were analyzed using scanning acoustic microscopy (C-SAM)
      and scanning electron microscopy (SEM) techniques. Thermal stresses in the joints
      were evaluated by means of a finite element model based on multilayer elastic
      strain analysis. The chemical reactions and their formation sequence at 750
      degrees C was predicted thermodynamically and observed experimentally both at 750
      and 800 degrees C. The C-SAM results gave evidence that the integrity of the
      porcelain-titanium joints are better in the sandblasted samples than in the
      electropolished ones, where defects were larger. SEM analyses of the same samples
      confirmed the C-SAM findings. Because the reaction layers are more continuous in
      the electropolished samples, cracks propagated more readily in these samples
      during the cooling procedure. Both thermodynamic calculations and experimental
      chemical analyses strongly indicate that the cause for the cracking of the
      reaction zone is thin layer of Ti (oxo)silicide and/or a relatively thick solid
      solution layer of Ti and oxygen.

PMID- 7814431
TI  - Biocompatibility of a new semisolid bioerodible poly(ortho ester) intended for
      the ocular delivery of 5-fluorouracil.
AB  - The biocompatibility of a new semisolid, hydrophobic poly(ortho ester) (POE)
      intended for controlled drug delivery to the eye was evaluated. The polymer was
      injected subconjunctivally in rabbits, and clinical and histologic examinations
      were performed 3, 10, 15, and 21 days after injection. Polymers injected as
      controls were an aqueous gel of sodium hyaluronate (SH), 1% in phosphate buffer,
      and medical grade silicone oil. After injection, the POE emulsified into small
      droplets and a focal eosinophilic reaction was noted at 3 days' implantation. At
      10 days' implantation, the POE was not identified in the implantation site and
      the inflammatory reaction had resolved, with fibroblasts being the predominant
      cell type. At 15 and 21 days, no POE was identified and normal appearing tissue
      was present in the injection site. Sodium hyaluronate was not inflammatory over
      the period of the implantations. Silicone oil induced a slight inflammation at 3
      days, with the presence of eosinophils and limited necrosis with cellular debris.
      Silicone oil was present in the implantation site at 3, 10, 15, and 21 days. The
      inflammatory response to the respective polymers was evaluated in the
      subconjunctival tissue. The inflammatory reaction was quantified at the implant
      site, adjacent subconjunctival tissues, and scleral and corneal stroma. The
      inflammatory cell densities in these respective tissue zones were determined, and
      the ratio of eosinophils over total inflammatory cells was calculated. POE did
      not become encapsulated with fibrous tissue, but biodegraded in a short time,
      indicating its potential for use after glaucoma filtration surgery.

PMID- 7814432
TI  - Tissue reaction to soft-tissue anchored percutaneous implants in rabbits.
AB  - This study reports on the soft-tissue response to titanium fiber mesh
      percutaneous implants. The implants were inserted in the backs of 15 rabbits. The
      surgical procedure was performed in two steps: implantation of the subcutaneous
      part of the implants and, after 3 months, fixation of the percutaneous part into
      the subcutaneous part. Two and 6 months after insertion the animals were
      sacrificed and the implants, with their surrounding tissues, were processed
      histologically. Light microscopic analysis demonstrated that only one implant
      showed considerable skin retraction in the percutaneous area. Around the rest of
      the implants no downgrowth or only a very limited epidermal downgrowth was
      observed. Furthermore, the fiber mesh material showed good biocompatible
      behavior. These results confirm the previous finding that sintered titanium
      fiberweb structures are effective for the stabilization of percutaneous devices
      located in soft tissues and can improve their performance.

PMID- 7814433
TI  - Effects of variation of prosthesis size on cement stress at the tip of a femoral
      implant.
AB  - With the resurgence of the use of bone cement in total hip arthroplasty, a
      renewed interest in techniques or designs that may reduce cement fixation failure
      has arisen. Analysis of the stresses at the tip of the prosthesis may suggest
      strategies to reduce loosening. This study analyzed stresses in the cement near
      the tip of a femoral component as a function of cement thickness, using a three
      dimensional finite element model. A section of an idealized circular femoral
      shaft with implanted prosthesis and cement was modeled with loading conditions
      representing the stance phase of gait. Increasing cement thickness from 2 to 5 mm
      by reducing the prosthesis diameter from 15 to 9 mm is predicted to reduce stress
      significantly in the cement mantle of a femoral implant. Peak tensile stresses
      are reduced 45%, whereas peak von Mises and shear stresses are reduced 40%. Such
      a reduction in stress can increase fatigue life by an order of magnitude. Peak
      interface tensile stresses occur on the medial side at the tip of the prosthesis
      in a transverse direction, indicating likelihood of failure due to debonding. The
      shear and tensile stresses predicted by our model greatly exceed the fatigue
      endurance limit values for both bulk cement and the cement-prosthesis interface,
      indicating the likelihood of premature fatigue failure, even allowing for
      considerable uncertainty. These analytical results suggest that the surgeon
      should adopt a strategy of selecting a prosthesis that permits a 5-mm cement
      mantle near the tip of the prosthesis.

PMID- 7814434
TI  - Antithrombogenicity of lumbrokinase-immobilized polyurethane.
AB  - Lumbrokinase is a potent fibrinolytic enzyme purified from the earthworm,
      Lumbricus rubellus. We immobilized 18 IU/cm2 of lumbrokinase to polyurethane
      using maleic anhydride methylvinyl ether copolymer (MAMEC) as an enzyme carrier,
      and the proteolytic and fibrinolytic activities of immobilized lumbrokinase were
      assayed. Immobilized lumbrokinase retained about 34% of its activity, compared
      with soluble lumbrokinase activity. Immobilized lumbrokinase showed stability
      against thermal inactivation and degradation and within a various pH range. The
      optimal pH of immobilized lumbrokinase shifted 1.0 pH unit upward compared with
      soluble enzyme. Upon exposure to the human whole blood, less amount of 125I
      fibrinogen was adsorbed to lumbrokinase-immobilized surface than to the
      polyurethane control surface. The lumbrokinase-immobilized surface showed less
      platelet adhesion than did the MAMEC-grafted surface. At the early stage of
      platelet adhesion, the number of adhered platelets increased on the lumbrokinase
      immobilized surface with increasing time; yet, the platelet number drastically
      decreased on the lumbrokinase-immobilized surface after 80 min incubation. This
      suggests that lumbrokinase-immobilized polyurethane digested the adsorbed
      fibrinogen and inhibited platelet adhesion on the surface, probably by inhibiting
      fibrinogen adsorption to be highly antithrombogenic. Clinical applications of
      this material to artificial organs should be developed in the near future.

PMID- 7814435
TI  - Fate and biocompatibility of three types of microspheres implanted into the
      brain.
AB  - The implantation of polymer devices in the brain that release neuroactive drugs
      locally and in a controlled manner is gaining increasing interest. The fates and
      tissue reactions of poly(epsilon-caprolactone), ethylcellulose, and polystyrene
      microspheres, prepared by the solvent evaporation method, radiosterilized by
      gamma-irradiation, and stereotactically implanted in rat brain have been studied
      by routine staining and immunohistochemistry. During the first few days after
      implantation, a nonspecific astrocytic brain tissue reaction was observed along
      with a macrophagous-microglial cell reaction typically found following any damage
      in the central nervous system, except in the presence of certain foreign body
      giant cells. Nine months into the experiment, microspheres appeared to be
      engulfed by histiocytic cells. The microsphere cluster was surrounded by a sheath
      composed of collagen and astrocytic cells. No necrosis was observed, suggesting
      the absence of toxicity. In some animals, however, an hydrocephalus developed as
      a result of obstruction of the medial ventricle by some microspheres.

PMID- 7814436
TI  - Production of spherical ZrO2-Y2O3 and ZnO particles.
AB  - In recent years substantial effort has been focused on the use of engineered
      ceramics for biomedical applications. To produce ceramic components with reliable
      and reproducible properties for such speciality applications, it is necessary to
      use high-purity raw material powders with specific properties. Fine ceramic
      particles having specific shapes and sizes are also required for conducting
      biocompatibility experiments. This article reports on the laboratory scale
      production, in an aerosol reactor, of spherical, submicron zirconia (partially
      stabilized by yttria; ZrO2-Y2O3) and zinc oxide (ZnO) particles by the thermal
      decomposition of mists generated from aqueous solutions of inorganic metal salt
      precursors. The particles produced were characterized by scanning electron
      microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy.

PMID- 7814437
TI  - Transmission electron and high-voltage electron microscopy of osteocyte cellular
      processes extending to the dental implant surface.
AB  - Examination of the morphology of osteocytes within the bone supporting endosteal
      dental implants was performed using conventional transmission and high-voltage
      transmission electron microscopy (HVEM). The in vivo dog model used 72 implants
      inserted into the premolar region of 18 experimental animals. Forty-eight
      implants in 12 dogs were used as anterior abutments for fixed bridges for periods
      up to 12 months. The mineralized matrix of the supporting bone was either
      directly apposed to the implant surface or was separated from the implant by a
      narrow region of unmineralized matrix. Osteocytes were routinely observed to be
      closely associated with the bone-implant interface, as well as at a distance from
      the implant. Osteocytes were found to extend cellular processes directly to the
      implant surface through canaliculi. The osteocyte processes contained
      microfilaments. The three-dimensional capabilities of HVEM elucidated the nature
      of these cell processes at the point of exit from the osteocyte, as the processes
      extended through the mineralized matrix, and as the processes terminated at the
      implant interface. This report suggests that avenues of communication may exist
      between the implant and the osseous cells, providing intriguing hypotheses
      regarding biomechanical forces and osteogenesis at the implant interface.
      Furthermore, an electron-dense deposit was observed upon the inner confines of
      the canalicular wall, upon the outer aspects of the osteocyte lacuna, and upon
      the outer aspect of the bone interfacing the implant.

PMID- 7814438
TI  - Interactions of human von Willebrand factor with a hydrophobic self-assembled
      monolayer studied by atomic force microscopy.
AB  - Human von Willebrand Factor (vWF) was studied by atomic force microscopy under
      physiologic buffer on a hydrophobic octadecyltrichlorosilane self-assembled
      monolayer. The self-assembled monolayer deposited on glass was sufficiently
      smooth (root mean square roughness = 0.25 +/- 0.12 nm) to permit identification
      of adsorbed vWF. Adhesion of the protein to the hydrophobic substrate was
      sufficient to allow repeated scanning by the atomic force microscope probe, and
      images of vWF on a submolecular scale were obtained. The frictional force between
      the surface and the protein was sufficient to withstand an applied lateral force
      of 19 nN. This result shows that vWF experiences strong interaction with a
      hydrophobic surface in aqueous media. Statistical analysis of adsorbed vWF shows
      that the protein is composed of large globular domains with elliptical cross
      sections of average dimensions 56 +/- 24 nm (major axis) 26 +/- 19 nm (minor
      axis), and 2.8 +/- 1.0 nm (height). Further analysis of the major axis dimension
      shows that the molecular chain of vWF contains two statistically different
      populations of domain size. However, no sequence order of the different domains
      within the individual molecule was found. On the basis of our analysis of the
      globular domains, we present a model describing the three-dimensional structure
      of vWF protomer adsorbed on a hydrophobic surface in a physiologic solution.

PMID- 7814439
TI  - Effect of molecular structure of poly(glycidyl ether) reagents on crosslinking
      and mechanical properties of bovine pericardial xenograft materials.
AB  - With the identification of the exacerbating effect of glutaraldehyde on
      calcification of heart valve materials, there exists a renewed interest in both
      alternative reagents and the effects of crosslinking on connective tissues. One
      potentially useful class of reagents are poly(glycidyl ether) compounds. We have
      examined 5 of these reagents with different molecular sizes and functionalities
      for their effects on mechanical properties and collagen denaturation (shrinkage)
      temperature. Samples of bovine pericardium were tested fresh or after 48 h
      fixation in one of the five compounds for denaturation temperature, stress-strain
      response, stress relaxation, plastic deformation, and fracture properties. Of the
      compounds tested, those with intermediate length backbones and 4 or 5 epoxide
      groups were most effective in producing intrahelical crosslinking and increased
      denaturation temperature over 48 h. However, in samples examined after 17 months
      of fixation, all reagents had equivalently increased the denaturation
      temperature. Examination of mechanical results revealed two distinct mechanisms
      for mechanical change. Observed shifting of the stress-strain curve to the right
      (due to shrinkage), increased plastic deformation, and some reduction of stress
      relaxation are all unrelated to denaturation temperature (and hence to changes in
      intrahelical crosslinking). An alternate mechanism, perhaps formation of
      intermolecular crosslinks may be responsible. Intrahelical crosslinking produces
      only lesser reductions in stress relaxation. Cross-comparison of reagents of
      differing molecular structure provides a useful tool toward increased
      understanding of the mechanical consequences of tissue crosslinking.

PMID- 7814440
TI  - In vivo reactions of Ca,P particle containing surface reactive glasses.
AB  - Four Ca,P particle containing surface reactive glass composites and two glasses
      (in the SiO2-CaO-P2O5-Na2O-Al2O3-B2O3 system) were implanted in the diaphyseal
      area of goat femora up to 24 weeks. Scanning electron microscopic, energy
      dispersive x-ray, and histological analysis were performed to evaluate the
      material-tissue interactions. A new type of integration mechanism was observed.
      Instead of the bone growing to the material surface, a gel-like silica formation
      appeared between the cortex bone and the material surface. In time the gel-like
      formation was replaced by a Ca,P layer. The results provided indirect evidence
      that pure silica gel formed in the tissues could also achieve an apatite layer
      formation and bone bonding on its surface.

PMID- 7814441
TI  - Effect of membrane potential on surface Ca2+ receptor activation in rat
      osteoclasts.
AB  - Osteoclasts are known to possess a divalent cation-sensitive receptor, the Ca2+
      receptor (CaR). The latter monitors changes in the local Ca2+ concentration
      generated as a result of hydroxyapatite dissolution. CaR activation elevates
      cytosolic [Ca2+] and thereby inhibits osteoclastic bone resorption. Recent
      studies have used Ni2+ as a surrogate CaR agonist to elicit changes in cytosolic
      [Ca2+]. This article examines the effects of membrane potential changes on the
      kinetics of the cytosolic [Ca2+] signal resulting from such Ni(2+)-induced CaR
      activation. Membrane potential was altered through variations in the
      extracellular [K] in combination with applications of the K+ ionophore,
      valinomycin. Membrane potential changes were confirmed by independent
      electrophysiological patch clamp studies of whole osteoclasts. The application of
      valinomycin produced a distinct, sustained elevation of cytosolic [Ca2+] in
      single fura 2-loaded cells, a "primary" response. This response was independent
      of valinomycin concentration (between 5 nM to 5 microM) and persisted in Ca(2+)
      free, EGTA-containing solutions. It also persisted both in high (105 mM) and low
      (5 mM) extracellular [K+]. A gradual "secondary" elevation of cytosolic [Ca2+]
      then followed with the continued application of valinomycin, but this was
      eliminated by sequestering the extracellular [Ca2+] or by increasing
      extracellular [K+] from 5 to 105 mM. In a separate set of experiments, the
      presence of 5 microM [valinomycin]-([K+] = 5 mM) prolonged the cytosolic [Ca2+]
      signal elicited by 50 microM-[Ni2+] application. These prolonged kinetics
      persisted in low extracellular [Ca2+] (zero-added Ca2+), but reverted to a rapid
      time-course in the presence of 105 mM-[K+] or at higher [Ni2+] (500 microM and 5
      mM). The experiments thus indicate that membrane voltage modifies the kinetics of
      CaR activation by Ni2+ and therefore suggests that the CaR is an integral protein
      in the osteoclast surface membrane.

PMID- 7814442
TI  - Immunolocalization of mitochondrial 3-hydroxy-3-methylglutaryl CoA synthase in
      rat liver.
AB  - We report the preparation of specific polyclonal antibodies raised against two
      synthetic peptides deduced from the cDNA sequence for the rat liver mitochondrial
      3-hydroxy-3-methylglutaryl Coenzyme A (HMG-CoA) synthase gene. Immunoelectron
      microscopy using these antibodies on hepatic cryoultrathin sections confirms the
      mitochondrial localization of this protein in hepatocytes. Immunofluorescence
      microscopy on frozen sections of adult rat liver revealed fluorescence inside all
      hepatocytes, with no evidence of zonation, indicating that ketogenesis may not be
      limited to specific regions of rat liver but is extended to all hepatocytes.

PMID- 7814443
TI  - Analysis of EPC-1 growth state-dependent expression, specificity, and
      conservation of related sequences.
AB  - The transcript for EPC-1 (early population doubling level (PDL) cDNA-1) is
      induced under conditions of growth arrest due to density-dependent contact
      inhibition and/or serum deprivation in early-passage but not in senescent WI-38
      fibroblasts. We have characterized the EPC-1 transcript with respect to its cell
      cycle regulation, tissue specificity, and interspecies conservation of related
      genomic sequences. In low density, quiescent (serum-deprived), early-passage
      fibroblasts that are stimulated to proliferate with fresh serum, steady-state EPC
      1 transcript levels are steadily reduced until they reach a basal level
      approximately 24 h after stimulation. However, when early-passage fibroblasts are
      made quiescent by both serum deprivation and density-dependent contact inhibition
      and then stimulated with serum, steady-state EPC-1 transcript levels remain
      relatively constant throughout a 36 h period following serum stimulation.
      Senescent WI-38 cells (> 95% life span completed) do not express EPC-1 under
      these conditions. We show that differences in the regulation of EPC-1 transcript
      levels in early-passage cells are due to differences in growth state rather than
      changes in cell density or contact. We also show that expression of the EPC-1
      transcript is limited to specific cell types and that related genomic sequences
      are found in all mammalian species examined as well as in the chicken.

PMID- 7814444
TI  - Tumor necrosis factor reduces proteoglycan synthesis in cultured endothelial
      cells.
AB  - Tumor necrosis factor (TNF)-induced disruption of vascular endothelial barrier
      function may be due in part to alterations in proteoglycan metabolism. To test
      this hypothesis, confluent endothelial cell monolayers were exposed for 24 h to
      500 or 1,000 U of TNF per milliliter of culture medium together with 20 microCi
      Na2 35SO4. HPLC anion-exchange separation of proteoglycans secreted into media of
      control as well as TNF-treated cultures revealed one major peak (representing 95%
      of total radioactivity) and one minor peak (representing 5% of total
      radioactivity), which eluted at 0.6 and 0.9 M NaCl, respectively. One single peak
      was obtained from control as well as TNF-treated endothelial cell monolayers and
      eluted at 1.2 M NaCl. TNF treatment did not change the total quantity of
      radioactive proteoglycans secreted into the media but significantly decreased the
      amount of proteoglycans in endothelial cell monolayers. However, TNF treatment
      did not alter the size or glycosaminoglycan (GAG) composition of the
      proteoglycans either in the media or in the cell monolayers. In addition, mRNA
      levels of specific proteoglycans, perlecan and biglycan, were measured upon TNF
      treatment, using Northern analysis. TNF treatment caused a dose-dependent
      decrease in mRNA levels for the core proteins of perlecan, a major heparan
      sulfate proteoglycan (HSPG), and biglycan in endothelial cultures. These results
      suggest that TNF decreases production of proteoglycans and alters normal
      endothelial cell proteoglycan metabolism which may be sufficient to impair
      endothelial barrier function.

PMID- 7814445
TI  - Interferon-gamma exerts its negative regulatory effect primarily on the earliest
      stages of murine erythroid progenitor cell development.
AB  - Interferon-gamma (INF-gamma) has been shown to suppress erythropoiesis and
      perhaps to contribute to the anemia of chronic disease. In this study we
      demonstrated that the concentration of INF gamma required to suppress murine
      burst forming unit-erythroid (BFU-E) growth was significantly less than that
      required to suppress colony forming unit-erythroid (CFU-E) growth. INF gamma
      acted at the most primitive step in erythroid progenitor cell differentiation and
      proliferation, as inhibition was maximal when added at the time of BFU-E culture
      initiation. Inhibition was progressively less if INF gamma addition was delayed
      after culture initiation. The effects of INF gamma on BFU-E did not require the
      presence of interleukin-1 alpha (IL-1 alpha), tumor necrosis factor-alpha (TNF
      alpha), or granulocyte macrophage colony stimulating factor (GM-CSF), as its
      effects were not neutralized by monoclonal antibodies against IL-1 alpha, TNF
      alpha, or GM-CSF. This applied whether INF gamma was added to culture with
      individual antibodies or with a combination of all three antibodies. INF gamma
      was not required for IL-1 alpha- or TNF alpha-induced suppression of BFU-E, as
      their effects were not neutralized by a monoclonal anti-INF gamma antibody. In
      contrast, GM-CSF-induced suppression of BFU-E was negated by the simultaneous
      addition of anti-INF gamma. We have previously shown that the addition of TNF
      alpha does not suppress BFU-E growth in cultures from marrow depleted of
      macrophages. Suppression did occur, however, if a small concentration of INF
      gamma that does not inhibit and increasing concentration of TNF alpha were added
      to culture, suggesting a synergistic effect between INF-gamma and TNF alpha.
      These observations suggest that INF gamma is a potent direct inhibitor of
      erythroid colony growth in vitro. It exerts its negative regulatory effect
      primarily on the earliest stages of erythroid progenitor cell differentiation and
      proliferation, as much higher doses are required to suppress late erythroid cell
      development. INF gamma is also involved in GM-CSF-induced inhibition of BFU-E
      colony growth.

PMID- 7814446
TI  - Mevalonate dependency of the early cell cycle mitogenic response to epidermal
      growth factor and prostaglandin F2 alpha in Swiss mouse 3T3 cells.
AB  - Lovastatin (LOV), a hydroxy-methylglutaryl-coenzyme A (HMGCoA) reductase
      competitive inhibitor, blocks epidermal growth factor (EGF)- or prostaglandin F2
      alpha (PGF2 alpha)-induced mitogenesis in confluent resting Swiss 3T3 cells. This
      inhibition occurs even in the presence of insulin, which potentiates the action
      of these mitogens in such cells. LOV exerts its effect in a 2-80 microM
      concentration range, with both mitogens attaining 50% inhibition at 7.5 microM.
      LOV exerted its effect within 0-8 h following mitogenic induction. Mevanolactone
      (10-80 microM) in the presence of LOV could reverse LOV inhibition within a
      similar time period. LOV-induced blockage of PGF2 alpha response is reflected in
      a decrease in the rate of cell entry into S phase. Neither cholesterol,
      ubiquinone, nor dolichols of various lengths could revert LOV blockage. In EGF-
      or PGF2 alpha-stimulated cells, LOV did not inhibit [3H]leucine or [3H]mannose
      incorporation into proteins, while tunicamycin, an inhibitor of N' glycosylation,
      prevented this last phenomenon. Thus, it appears that LOV exerts its action
      neither by inhibiting unspecific protein synthesis nor by impairing the N'
      glycosylation process. These findings strongly suggest that either EGF or PGF2
      alpha stimulations generate early cell cycle signals which induce mevalonate
      formation, N' glycoprotein synthesis, and proliferation. The causal relationship
      of these events to various mechanisms controlling the onset of DNA synthesis is
      also discussed.

PMID- 7814447
TI  - Differential effects of superoxide, hydrogen peroxide, and hydroxyl radical on
      intracellular calcium in human endothelial cells.
AB  - Changes in intracellular Ca2+ homeostasis are thought to contribute to cell
      dysfunction in oxidative stress. The hypoxanthine-xanthine oxidase system (X-XO)
      mobilizes Ca2+ from intracellular stores and induces a marked rise in cytosolic
      calcium in different cell types. To identify the reactive O2 species involved in
      the disruption of calcium homeostasis by X-XO, we studied the effect of X-XO on
      [Ca2+]i by spectrofluorimetry with fura-2 in human umbilical vein endothelial
      cells (HUVEC). The [Ca2+]i response to X-XO was essentially diminished by
      superoxide dismutase (SOD) (200 U/ml) and catalase (CAT) (200 U/ml), which
      scavenge the superoxide anion, O2-, or H2O2, respectively. The [Ca2+]i increase
      stimulated by 10 nmol H2O2/ml/min, generated from the glucose-glucose oxidase
      system, or 10 microM H2O2, given as bolus, was about a third of that induced by X
      XO (10 nmol O2-/ml/min) but was comparable to that induced by X-XO in the
      presence of SOD. The X-XO-stimulated [Ca2+]i increase was significantly reduced
      by 100 microM o-phenanthroline, which inhibits the iron-catalysed formation of
      the hydroxyl radical. On the other hand, the [Ca2+]i response to low dose X-XO (1
      nmol O2-/ml/min) was markedly enhanced in the presence of 1 microM H2O2, which
      itself had no effect on [Ca2+]i. More than 50% of this synergistic effect was
      prevented by o-phenanthroline. These results indicate that the effect of X-XO on
      calcium homeostasis appears to result from an interaction of O2- and H2O2, which
      could be explained by the formation of the hydroxyl radical.

PMID- 7814448
TI  - Multiple sites of vanadate and peroxovanadate action in Xenopus oocytes.
AB  - In Xenopus laevis oocytes, the insulin mimics, vanadate and peroxovanadates (PV),
      stimulated the uptake of 3H-2-deoxyglucose and incorporation of 35S-methionine
      into protein. For both hexose transport and protein synthesis, peroxovanadates
      (produced by reacting vanadate and H2O2) were at least as potent as vanadate.
      Microinjection of peroxovanadates into the oocytes stimulated 2-deoxyglucose
      uptake. However, methionine incorporation was not stimulated by microinjection of
      peroxovanadate or vanadate solutions. Consistent with these results and with the
      possibility that vanadate and peroxovanadates enter the cell on a phosphate
      transporter, raising the medium phosphate concentration from 1 mM to 10 mM
      blocked vanadate-stimulated hexose transport and partially reduced
      peroxovanadates stimulation of hexose transport. Increased medium phosphate did
      not reduce stimulation of protein synthesis by either effector. Taken together,
      these data indicate that vanadate/peroxovanadates act at both intracellular and
      extracellular sites. Action at the former stimulates hexose uptake and action at
      the latter, protein synthesis.

PMID- 7814449
TI  - Mitotic cycle reactivation in terminally differentiated cells by adenovirus
      infection.
AB  - Different cell types (e.g., neurons, skeletal and heart myocytes, adipocytes,
      keratinocytes) undergo terminal differentiation, in which acquisition of
      specialized functions entails definitive withdrawal from the cell cycle. Such
      cells are distinct from quiescent (reversibly growth-arrested) cells, such as
      contact-inhibited fibroblasts. Terminally differentiated cells can not be induced
      to proliferate by means of growth factor stimulation or transduction of cellular
      oncogenes. An important first step toward defining the molecular basis for such
      unresponsiveness is to find a practical means to overcome the proliferative
      block. Furthermore, determining whether terminally differentiated, postmitotic
      cells still retain a potential competence for proliferation that can be
      reactivated would have important theoretical and practical implications. To
      address these questions, we exploited the properties of adenoviruses. These
      viruses can infect postmitotic cells and express E1A, a powerful activator of
      proliferation in reversibly growth-arrested cells. We infected terminally
      differentiated skeletal muscle cells and adipocytes with human adenovirus type 5
      or 12, obtaining full reentry into the cell cycle, including DNA synthesis,
      mitosis, cytokinesis, and extended proliferation. Similar results were obtained
      with established cell lines and primary cells belonging to several species, from
      quail to humans. Genetic analysis indicated that the smaller splice product of
      E1A, E1A 12S, is sufficient to induce cell cycle reactivation in otherwise
      permanently nonmitotic cells. These results demonstrate that terminally
      differentiated cells retain proliferative potential and establish adenovirus as a
      convenient and powerful means to force such cells to reenter the cell cycle.

PMID- 7814450
TI  - Epidermal growth factor rapidly impairs activation of p34cdc2 protein kinase in
      HeLa cells at the G2-M boundary.
AB  - Epidermal growth factor (EGF) has been shown rapidly to inhibit the transition
      from G2 phase to mitosis: beyond this transition point the cells are refractory
      to EGF (Kinzel et al., 1990, Cancer Res., 50:7932-7936). Using synchronized HeLa
      cells, EGF has now been shown to induce an overall decrease of the histone H1
      kinase activity of p34cdc2 after 20 min of treatment, a time course which
      correlates with the number of cells in metaphase. The kinase level of actively
      mitotic cells is not altered by EGF. Neither the amount of p34cdc2 protein
      present nor that of Cyclin B in influenced by EGF, and the formation of the
      p34cdc2/Cyclin B complex is also unaffected. The use of antiphosphotyrosine
      antibodies, however, showed that p34cdc2 from cultures treated with EGF was more
      intensely stained than that of control cells, indicating that EGF treatment
      prevents the tyrosine dephosphorylation which is required for expression of the
      protein kinase activity of the complex. Taken together, the results show that EGF
      in HeLa cells very rapidly prevents the p34cdc2/Cyclin B complex from expressing
      kinase activity at the G2-M boundary, which appears to be the cause for the
      inhibition in G2 phase.

PMID- 7814451
TI  - Expression of a voltage-dependent potassium current precedes fusion of human
      muscle satellite cells (myoblasts).
AB  - Using the whole-cell recording patch clamp technique in clonal cultures of human
      muscle satellite cells (SC), we studied a voltage-gated potassium current
      analogous to the delayed rectifier current (IKdr) described in adult human
      skeletal muscle. This current was absent in proliferating SC cultured in a growth
      medium containing 15% serum, except when the SC approached the end of their
      replicative life (between 77 and 124 days in culture); at that time,
      approximately 50% of the SC possessed IKdr. In contrast, IKdr was expressed
      within less than 4 days in approximately 70% of the SC cultured in a serum-free
      medium (SFM) and within 24 h in differentiating medium. We believe that IKdr may
      be a characteristic feature of fusion-component SC and that it may be involved in
      the fusion process for the following reasons: 1) after the transfer in
      differentiating medium, cultures of SC in which the expression of IKdr was
      previously promoted by exposure to SFM were found to fuse immediately, without
      the initial 24 h lag time observed in control sister cultures; 2) in the latter
      "naive" SC, IKdr was expressed during the first day in differentiating medium,
      before SC began to fuse; 3) most of the SC that did not fuse even after weeks of
      exposure to differentiating medium did not express IKdr; 4) TEA, at a
      concentration of 3 mM, reduces the amplitude of IKdr by 55% and the fusion index
      by 55-67%.

PMID- 7814452
TI  - EGF receptor-mediated signals are differentially modulated by concanavalin A.
AB  - NIH 3T3 cells expressing high levels of the human epidermal growth factor (EGF)
      receptor were used to examine the effects of the lectin concanavalin A (Con A) on
      EGF-mediated signaling events. Proliferation of NIH 3T3 cells expressing high
      levels of the human EGF receptor was inhibited in a dose-dependent manner by Con
      A. At the same time, Con A also inhibited both dimerization and tyrosine
      phosphorylation of the EGF receptor. Tyrosine phosphorylation of the enzyme
      phospholipase C-gamma, a substrate of the phosphorylated EGF receptor kinase, was
      also inhibited. In contrast, EGF-stimulated changes in pH, calcium, and levels of
      inositol phosphates were unaffected by the presence of Con A. These results
      indicate that certain signals (changes in the levels of intracellular calcium,
      pH, and inositol phosphates) mediated by EGF binding to its receptor still occur
      when receptor dimerization and phosphorylation are dramatically decreased,
      suggesting that multiple independent signals are transmitted by the binding of
      EGF to its receptor.

PMID- 7814453
TI  - Disruption of microtubules in vivo by vincristine induces large membrane
      complexes and other cytoplasmic abnormalities in megakaryocytes and platelets of
      normal rats like those in human and Wistar Furth rat hereditary
      macrothrombocytopenias.
AB  - Abnormal organization of platelet microtubules is associated with abnormal
      platelet formation in hereditary macrothrombocytopenias such as the gray platelet
      syndrome, May-Hegglin anomaly, and Epstein's syndrome, and that of the Wistar
      Furth rat, suggesting that aberrant microtubule organization may contribute to
      defective platelet formation in these clinical entities. Here, we examined the
      consequence of microtubule disruption on the organization of megakaryocyte
      cytoplasmic organelles using the microtubule depolymerizing agent, vincristine
      (VCR). Wistar rat bone marrow was fixed and processed for transmission electron
      microscopy after VCR administration alone, after 5-fluorouracil (5-FU)
      administration alone, or after 5-FU followed by intravenous injection of 0.1-1.0
      mg/kg VCR for intervals of 30 min to 8 hr. 5-FU was given to increase
      megakaryocyte frequency to facilitate ultrastructural evaluations. VCR alone or
      in combination with 5-FU caused formation of large membrane complexes in the
      cytoplasm of Wistar rat megakaryocytes at all dosages studied, identical to those
      found in megakaryocytes of human hereditary macrothrombocytopenias and the Wistar
      Furth rat. The proportion of megakaryocytes with these large membrane complexes
      increased with time after 5-FU and VCR, and was maximal (approximately two-thirds
      of megakaryocytes) at VCR dosages of 0.75-1.0 mg/kg. The majority of
      megakaryocytes displayed other abnormalities, including blebbing of plasma
      membranes, an increased number of dense compartments, dilated demarcation
      membrane (DMS) channels, which contained dense material immunocytochemically
      identified as secreted alpha-granule proteins, and an increased incidence of
      emperipolesis. Rats administered 5-FU alone did not demonstrate these
      abnormalities, with the exception of an increase in dense compartments. Platelets
      from rats treated with VCR alone or 5-FU and VCR also showed abnormalities
      including membrane complexes, rounded shape, formation of tubulin paracrystals,
      development of membrane blebs, and the presence of proteinaceous material within
      the cisternae of the surface-connected canalicular system (SCCS). The membrane
      complexes in platelets of 5-FU-, VCR-treated Wistar rats as well as untreated
      Wistar Furth rats were composed of elements of both the SCCS and dense tubular
      system; membrane complexes in megakaryocytes of 5-FU-, VCR-treated rats were
      composed of both DMS and smooth endoplasmic reticulum. We conclude that intact
      microtubules play a major role in the organization of the megakaryocyte DMS and
      may contribute to the stability of megakaryocyte alpha-granules.

PMID- 7814454
TI  - Decreased levels of alpha 1(I) procollagen mRNA in dermal fibroblasts grown on
      fibrin gels and in response to fibrinopeptide B.
AB  - We have investigated human neonatal fibroblast synthetic activity in response to
      fibrin substrates and components of fibrin formation and degradation. Greater
      than threefold downregulation of procollagen mRNA levels was seen 24 hours after
      fibroblasts were grown on fibrin gels as compared to tissue culture plastic. This
      downregulation occurred in both reptilase-generated fibrin (retention of
      fibrinopeptide B) and thrombin-generated fibrin (loss of both fibrinopeptide A
      and B). However, fibroblasts grown on fibrin retained their capacity to respond
      to the stimulatory action of transforming growth factor (TGF)-beta 1. Fibroblasts
      seeded on reptilase-generated fibrin displayed an abnormal morphology manifested
      by dendritic appearance and cell rounding, while fibroblast attachment was
      enhanced by 30% on thrombin-generated fibrin substrate (P < 0.02).
      Fibrinopeptides A and B, which are generated during fibrin formation, increased
      and decreased procollagen mRNA levels, respectively. Tissue plasminogen activator
      (t-PA) increased procollagen mRNA and TGF-beta 1 levels as early as 6 hours after
      cells were grown on tissue culture plastic, but this stimulation did not occur in
      cells cultured on a fibrin substrate. We conclude that alpha 1(I) procollagen
      mRNA levels in cultures of human dermal fibroblasts are consistently down
      regulated by a fibrin substrate and are directly and profoundly influenced by
      complex interactions between components involved in the formation and removal of
      fibrin.

PMID- 7814456
TI  - Complete inherited deficiency of the fourth complement component in a child with
      systemic lupus erythematosus and his disease-free brother in a north African
      family.
AB  - Although null alleles of complement C4 genes (C4A*Q0 and C4B*Q0) are frequent in
      the normal population, the occurrence of two null alleles on the same chromosome
      is very rare and therefore complete C4 deficiency is exceptional. We describe a
      16-year-old North African boy who presented with systemic lupus erythematosus
      with renal involvement and persistent undetectable classical pathway activity and
      C4 protein and hemolytic activity in plasma, with normal C3 levels. Similar
      complement abnormalities were observed in his healthy 12-year-old brother.
      Complete C4 deficiency was documented in the two brothers by investigation of the
      family and the lack of C4A and C4B bands upon phenotyping of C4. Southern blot
      analysis of the C4/CYP21 gene organization in the family indicated that the
      deficiency resulted from a deletion of the C4B/CYP21A genes associated with
      nonexpression of a C4A gene. The double-null haplotype was found to be associated
      with homozygous A2 B17 C2C BFF C4 AQ0 BQ0 DR7 HLA haplotype. Thus, similar C4
      deficiencies with HLA identity may lead to different clinical presentations.

PMID- 7814455
TI  - Reassessment of the impact of mucosal immunity in infection with the human
      immunodeficiency virus (HIV) and design of relevant vaccines.

PMID- 7814457
TI  - Inhibition of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL
      1 beta) secretion but not IL-6 from activated human peripheral blood monocytes by
      a new synthetic demethylpodophyllotoxin derivative.
AB  - A newly synthesized demethylpodophyllotoxin derivative, 4-O-butanoyl-4'
      demethylpodophyllotoxin (BDPT) or BN58705, has recently been shown to exert a
      potent cytotoxic activity in vitro against a variety of drug-resistant human
      tumor cell lines. The effect of this agent on effector cells of the immune
      system, however, has not been examined. The present study investigated the effect
      of BDPT on the response of activated human peripheral blood derived monocytes
      (PBM) to secrete cytokines. Activation of PBM overnight with LPS, IFN-gamma, or
      PMA resulted in secretion into the supernatant of TNF-alpha, IL-1 beta, IL-6, and
      IL-8 as assessed by ELISA. The addition of BDPT to the stimulated cultures
      resulted in significant inhibition of TNF-alpha and IL-1 beta secretion, whereas
      the secretion of IL-6 and IL-8 was not affected. The selective inhibition of TNF
      alpha and IL-1 beta secretion by BDPT-treated PBM was observed with all three
      stimuli tested. The inhibitory effect mediated by BDPT was concentration
      dependent and was optimal at 6-20 microM. Time kinetic analysis indicated that
      the inhibition of secretion was rapid and detected as soon as 2 hr following
      stimulation of the PBM and lasted for as long as 24 hr. A comparison was made
      between BDPT and pentoxyfilline, a xanthine-derived phosphodisterase inhibitor
      that was reported to inhibit TNF-alpha and IL-1 beta secretion by PBM. Both BDPT
      and PTX showed similar time kinetics and patterns of inhibition.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7814458
TI  - Age-related ranges of memory, activation, and cytotoxic markers on CD4 and CD8
      cells in children.
AB  - The expression of markers defining functional subpopulations on the surface of
      CD4 and CD8 cells changes with disease. To monitor these changes in children, it
      is important to establish the age-related normal changes in marker expression due
      to maturation of the immune system. We have studied the expression of several
      functionally important molecules on both CD4 and CD8 cells in 168 children (aged
      0-122 months) using monoclonal antibodies and flow cytometry. Our results show
      that the percentage of CD4 cells decreases with age, while the CD8 percentage
      increases, resulting in a decrease in the CD4/CD8 ratio. The expression of CD45RO
      and CD29 increases with age, while CD45RA expression decreases, both on CD4 and
      CD8 cells. The expression of HLA-DR on both CD4 and CD8 cells, and of CD11a and
      CD57 on CD8 cells, is less clearly age dependent. The relationships between the
      marker percentages and age were not straightforward; the standard deviations and
      the skewness, as well as their mean values, varied as a function of age. The
      changes were modeled for each marker and age-specific centiles are presented.

PMID- 7814459
TI  - Evidence for an abnormal profile of interleukin-4 (IL-4), IL-5, and gamma
      interferon (gamma-IFN) in peripheral blood T cells from patients with allergic
      eosinophilic gastroenteritis.
AB  - Allergic eosinophilic gastroenteritis is characterized by elevated total IgE,
      specific IgE to food antigens, and eosinophilia of tissue and blood. Because the
      lymphokines IL-4, IL-5, and gamma-interferon, regulate IgE synthesis, and
      eosinophilopoiesis in vitro, we examined whether there is an imbalance in their
      production in allergic eosinophilic gastroenteritis. To explore this hypothesis,
      three adult patients with allergic eosinophilic gastroenteritis were studied.
      Flow cytometric studies of peripheral blood mononuclear cells from these patients
      did not reveal evidence of T cell activation or disturbance of T cell numbers or
      subsets. T cells were capable of normal mitogenic activation in vitro. IL-4 and
      IL-5 production were markedly elevated with mitogenic stimulation. Most IL-4 and
      IL-5 production was by CD4+ T cells. Synthesis of IL-5 by CD4+ T lymphocytes in
      three patients and CD8+ T lymphocytes in two patients occurred in the absence of
      mitogen. Mitogen-stimulated GM-CSF and gamma-interferon synthesis by CD4+ T cells
      was normal. Lymphokine mRNA in total cellular RNA derived from endoscopic
      biopsies was examined by reverse transcription/polymerase chain reaction. Mucosal
      biopsies from control subjects and most biopsies from allergic eosinophilic
      gastroenteritis patients contained less than 10(-8) micrograms IL-5 mRNA/1
      microgram total cellular mRNA. gamma-Interferon mRNA was not detected by reverse
      transcription/polymerase chain reaction in biopsies from patients with allergic
      eosinophilic gastroenteritis but was present in controls. These lymphokine
      abnormalities are consistent with the elevated IgE and eosinophilia seen in
      allergic eosinophilic gastroenteritis and suggest that strategies targeting T
      lymphocytes may be efficacious in treatment of this disease.

PMID- 7814460
TI  - The presence of anti-carcinoembryonic antigen (CEA) antibodies in the sera of
      patients with gastrointestinal malignancies.
AB  - Using an enzyme-linked immunoassay we tested the sera of 71 patients with
      digestive system cancer, 35 patients with various nonmalignant disorders, and 28
      normal individuals for anti-CEA activity. Antibodies were found in the sera of
      51% of the patients. Most of the patients positive for the antibodies (70%) had
      no evidence of metastatic disease. Fewer than 10% of the sera from control groups
      had anti-CEA activity. The authors concluded that the patients suffering from
      cancer of the GI system are capable of producing tumor-specific antibodies. These
      antibodies could be used as a tumor marker and/or as a possible index for the
      function of the immune system. The presence of a large tumor mass could lead to
      the removal of these antibodies from the circulation.

PMID- 7814461
TI  - Neonatal lupus erythematosus with cardiac involvement in offspring of mothers
      with experimental systemic lupus erythematosus.
AB  - Neonatal lupus erythematosus (NLE) syndrome is characterized by a transient
      dermatitis, a variety of systemic and hematological abnormalities, and isolated
      cases of congenital complete heart block. The latter has been reported to be due
      to the presence of autoantibodies specific to La (SS-B) and/or Ro (SS-A). As
      female mice with experimental systemic lupus erythematosus (SLE) induced by
      immunization with the human monoclonal anti-DNA antibody bearing the 16/6 Id
      produce variety of autoantibodies including anti-Ro and anti-La antibodies, we
      looked for NLE related symptoms in the murine model. Offspring of BALB/c mice
      with SLE possessed high levels of autoantibodies that declined gradually till
      reduced to normal levels at day 60 after delivery. Electrocardiograms recorded in
      groups of offspring from mothers with experimental SLE indicated that a high
      percentage of the offspring had defects in their conductive system including
      first-, second-, and third-degree heart block, significant bradycardia, and a
      wide QRS complex. In contrast, a normal pattern was observed in offspring of
      healthy mothers.

PMID- 7814462
TI  - Isotypic distribution of anti-pyruvate dehydrogenase antibodies in patients with
      primary biliary cirrhosis and their family members.
AB  - IgG subclasses of anti-pyruvate dehydrogenase (PDH) antibodies were determined in
      72 patients with primary biliary cirrhosis. All isotypes were detected, but IgG3,
      IgG1, and IgG2 predominated independently or in association. An average of 33.3
      +/- 19.1% of the anti-PDH IgG was IgG1 (mean optical density, 0.863 +/- 0.783, vs
      0.053 +/- 0.038 in the normal controls), 25.0 +/- 17.8 IgG2 (0.652 +/- 0.656 vs
      0.062 +/- 0.030), 39.5 +/- 23.4% IgG3 (1.140 +/- 0.917 vs 0.010 +/- 0.023), and
      2.4 +/- 7.4% IgG4 (0.060 +/- 0.182 vs 0.012 +/- 0.007). Anti-PDH IgG were
      restricted to IgG1 in the family members of patients (0.180 +/- 0.403).

PMID- 7814463
TI  - Vibrio cholerae O139 Bengal.

PMID- 7814464
TI  - Diagnosis of genital Chlamydia trachomatis infections in asymptomatic males by
      testing urine by PCR.
AB  - An enzyme-linked immunosorbent assay (EIA) (MikroTrak; Syva) was compared with
      PCR (Amplicor; Roche) for detection of Chlamydia trachomatis in first-void urine
      (FVU) from 184 men attending a skin and venereal disease clinic. The prevalence
      of C. trachomatis in the population studied was 18.5%. Discrepant results between
      Syva EIA and Roche PCR were retested by using major outer membrane protein primer
      based PCR. After retesting, the sensitivity, the specificity, and the positive
      and negative predictive values for the Syva EIA were 85.3, 100, 100, and 77.5%,
      respectively, and those for the Roche PCR 100, 100, 100, and 100%, respectively.
      It was concluded that PCR provides a highly sensitive and specific noninvasive
      screening method for genital chlamydial infection in asymptomatic men.

PMID- 7814465
TI  - Description of Leeds Acinetobacter Medium, a new selective and differential
      medium for isolation of clinically important Acinetobacter spp., and comparison
      with Herellea agar and Holton's agar.
AB  - Acinetobacter spp. are responsible for an increasing number of opportunistic,
      nosocomial infections. They have been isolated from diverse inanimate objects in
      the hospital environment and are resistant to most of the commonly used
      antibiotics. Existing media for the isolation of Acinetobacter spp. are either
      nonselective, allowing the growth of unwanted bacteria, or too inhibitory,
      inhibiting the growth of many Acinetobacter strains. For the rapid isolation and
      effective control of Acinetobacter infection, a new selective and differential
      medium, Leeds Acinetobacter Medium (LAM), has been developed to isolate
      Acinetobacter spp. from clinical and environmental sources. The concentration of
      antibiotics and other ingredients in this medium have been determined according
      to the results of MIC and viable counts performed for these ingredients. LAM was
      compared with other selective and differential media for the isolation of
      Acinetobacter spp. from a local hospital environment and proved to be better in
      terms of recovery and selectivity.

PMID- 7814466
TI  - Transmission of the human polyomavirus JC virus occurs both within the family and
      outside the family.
AB  - JC polyomavirus (JCV) is a ubiquitous symbiote in the human population, infecting
      children asymptomatically and then persisting in renal tissue. We reevaluated the
      urinary excretion of JCV in subjects in various age groups using PCR. The
      detection rate for urinary JCV DNA was 9 to 17% until the age of 20 years; this
      rate increased dramatically to about 46% at the ages of 20 to 29 years and then
      increased gradually with age. Therefore, it appears that in most people excretion
      of JCV begins at the age of 20 to 29 years, which is earlier than suggested
      previously. Next, we studied the way in which JCV is spread in the human
      population. We selected eight Japanese families in which both parents and
      children excreted JCV in their urine. Their JCV subtypes were determined by PCR
      amplification of a JCV DNA fragment; this was followed by restriction enzyme
      analysis. JCV species in all JCV-positive family members were classified into
      either of the two subtypes, subtypes CY and MY, which are prevalent in the
      Japanese population. The following features of JCV subtype distribution were seen
      in the families: (i) both subtypes were detected in children of five of the eight
      families, and (ii) of 21 children who excreted JCV, 14 children excreted the same
      subtypes excreted by their mothers or fathers, while the remainder (7 children)
      excreted subtypes different from those excreted by their parents. These features
      suggest that JCV is transmitted both within the family and outside the family.
      The data also indicate that vertical transmission is not common in the spread of
      JCV.

PMID- 7814467
TI  - Molecular typing of Cryptococcus neoformans serotype D clinical isolates.
AB  - Cryptococcus neoformans serotype A is responsible for the majority of
      cryptococcal infections in AIDS patients. In France, approximately 17% of the
      patients are infected with serotype D, regardless of their human immunodeficiency
      virus status. In a retrospective study of 273 patients, we found that serotype D
      was unevenly distributed in France. We wondered if this was related to the
      yeast's genetic background. We used karyotyping and DNA fingerprints generated by
      UT-4p to analyze 40 serotype D clinical isolates. We found an extensive
      polymorphism, with only two conserved karyotypes from drug-addicted patients
      living in the same area. Although highly variable, the DNA fingerprints were
      classified into 10 groups. Four pairs of isolates were identical; three of these
      pairs were from patients living in the same area, but there was no other
      correlation with the geographical area. The two isolates with identical
      karyotypes belonged to the same fingerprint group. Five of the six isolates that
      made up fingerprint group I were recovered from drug-addicted patients (P <
      0.002; chi-square), and all five isolates found in fingerprint group III were
      from male homosexual patients (P < 0.02). Finally, five of the seven isolates
      from patients with cryptococcal pneumonia were classified as fingerprint group V
      (P < 0.04). These results suggest that there are possible relationships between
      characteristics of the isolates and body localization or even risk factors.
      Results of the present study warrant other studies on isolates of all serotypes
      and on isolates from clinical and environmental sources.

PMID- 7814468
TI  - Development and application of an enzyme immunoassay for coronavirus OC43
      antibody in acute respiratory illness.
AB  - Study of coronavirus OC43 infections has been limited because of the lack of
      sensitive cell culture systems and serologic assays. To improve this
      circumstance, we developed an indirect enzyme immunoassay (EIA) to detect serum
      antibody to OC43. Antigen (100 ng) prepared by polyethylene glycol precipitation
      provided optimal results without a postcoat procedure. Evaluation of intraplate
      variation indicated that a > or = 2.5-fold increase in serum titer was
      significant. Sixteen of 18 (89%) paired serum samples with previously identified,
      reproducible increases in the level of hemagglutination inhibition (HAI) antibody
      to OC43 also showed significant increases as detected by EIA. Specificity for the
      EIA was established with paired sera obtained from persons given influenza
      immunizations or experiencing a respiratory infection. No rise in antibody titers
      occurred among 33 persons with documented coronavirus 229E infection. EIA was
      then performed on each of 419 paired serum samples from ambulatory chronic
      obstructive pulmonary disease patients and healthy older adults, from asthmatic
      adults presenting for emergency room treatment, and from persons hospitalized
      with acute respiratory symptoms. Twenty-three antibody rises to OC43 were
      detected; only nine of these were detected by the HAI test, and the HAI test did
      not detect any increases in antibody titers that were not detected by EIA.
      Nineteen of 25 coronavirus OC43 infections for which a month of infection could
      be assigned occurred between November and February. Overall, 4.4% of acute
      respiratory illnesses in the studied populations were associated with a
      coronavirus OC43 infection.

PMID- 7814469
TI  - Monoclonal antibody capture enzyme immunoassay for detection of Paracoccidioides
      brasiliensis antibodies in paracoccidioidomycosis.
AB  - Four murine monoclonal antibodies (MAbs 17C, 21A, 21F, and 32B) raised against
      the 43-kDa glycoprotein of Paracoccidioides brasiliensis were tested in a capture
      enzyme immunoassay (EIA) for the detection of specific human anti-gp43
      immunoglobulin G in patients with paracoccidioidomycosis (PCM). All MAbs reacted
      similarly in the assay. These MAbs, which detected anti-gp43 at levels of as low
      as 500 pg/ml, were demonstrated to specifically recognize at least two different
      epitopes in gp43 binding assays. Specific antibodies in the sera of patients with
      active PCM were detected at dilutions of as high as 1:819,200, and the
      reactivities of patient sera, as measured by optical densities, were found to be
      significantly higher than those of control sera. The comparison between classical
      ELISA and our capture enzyme immunoassay showed that both sensitivity and
      specificity were greatly improved by the latter. These MAbs represent the first
      specific reagents to P. brasiliensis described for use in serological tests for
      PCM.

PMID- 7814470
TI  - PCR for capsular typing of Haemophilus influenzae.
AB  - A PCR method for the unequivocal assignment of Haemophilus influenzae capsular
      type (types a to f) was developed. PCR primers were designed from capsule type
      specific DNA sequences cloned from the capsular gene cluster of each of the six
      capsular types. PCR product was amplified only from the capsular type for which
      the primers were designed. Product was confirmed by using either an internal
      oligonucleotide or restriction endonuclease digestion. A total of 172 H.
      influenzae strains of known capsular type (determined genetically) comprising all
      capsular types and noncapsulate strains were tested by PCR capsular typing. In
      all cases the PCR capsular type corresponded to the capsular genotype determined
      by restriction fragment length polymorphism analysis of the cap region. When used
      in conjunction with PCR primers derived from the capsular gene bexA, capsulate,
      noncapsulate, and capsule-deficient type b mutant strains could be
      differentiated. PCR capsular typing overcomes the problems of cross-reaction and
      autoagglutination associated with the serotyping of H. influenzae strains. The
      rapid and unequivocal capsular typing method that is described will be
      particularly important for typing invasive H. influenzae strains isolated from
      recipients of H. influenzae type b vaccine.

PMID- 7814471
TI  - Genomic fingerprinting of Mycobacterium bovis from cattle by restriction fragment
      length polymorphism analysis.
AB  - Two insertion sequences, IS6110 and IS1081, specific to the tuberculosis complex
      mycobacteria and a highly reiterated DNA element (pTBN12) cloned from
      Mycobacterium tuberculosis were systematically used to identify restriction
      fragment length polymorphism (RFLP) types among bovine isolates of Mycobacterium
      bovis in Northern Ireland. In a sample of 109 isolates, probes IS6110, IS1081,
      and pTBN12 identified 10, 2, and 12 distinct patterns, respectively. By combining
      the patterns generated by the three probes it was possible to identify 28
      distinct RFLP types. The standard protocol advocated for RFLP analysis of M.
      tuberculosis was used and would facilitate computer-based gel documentation and
      image analysis to establish a database of M. bovis types for large-scale
      epidemiological studies. These procedures will facilitate interlaboratory
      comparisons of M. bovis isolates and will help to elucidate the precise
      epidemiology of bovine tuberculosis in different countries.

PMID- 7814472
TI  - Detection of enterotoxigenic Escherichia coli in stool samples by using
      nonradioactively labeled oligonucleotide DNA probes and PCR.
AB  - The detection of heat-labile enterotoxin LT-A and heat-stable enterotoxin ST Ia
      and ST Ib genes from enterotoxigenic Escherichia coli (ETEC) by using
      oligonucleotide DNA probes and the PCR was evaluated in reconstruction
      experiments and by testing stool specimens from 29 healthy subjects and from 50
      patients with diarrhea who had returned from the (sub)tropics. ETEC strains were
      detected in concentrations ranging from 10(6) to 10(8) CFU/g of feces when
      oligonucleotide probes were applied to colony blots from five randomly picked E.
      coli-like colonies from CLED (cystine lactose electrolyte deficient) agar plates
      inoculated with the feces. When these probes were applied to blots from whole
      stool cultures collected from the agar plates (sweep blot), the detection limit
      was 10(6) CFU/g of feces. PCR of the sweep material could detect toxin genes when
      the concentration of ETEC strains was 10(2) CFU/g of feces. Results obtained with
      stool specimens from 29 healthy control subjects were negative. Testing stool
      specimens from 50 patients confirmed the observation that the number of samples
      containing ETEC enterotoxin genes was higher when PCR of sweeps was used than
      when oligonucleotide DNA probe hybridization of either sweep blots or colony
      blots was used. Furthermore, PCR of sweeps is an easy and rapid method which does
      not require DNA extraction and purification from fecal specimens.

PMID- 7814473
TI  - Flavobacterium meningosepticum, a pathogen in birds.
AB  - Five bacterial isolates were recovered from various diseased birds (chickens, a
      pigeon, and a zebra finch) and were identified as Flavobacterium meningosepticum.
      Four of them were isolated in pure or nearly pure culture of samples from
      internal organs, and one strain was isolated in mixed culture of a tarsal joint
      fluid sample. Except for the last case, there was no evidence of other disease
      agents. By using phenotypic, chemotaxonomic, and genomic methods, the strains
      were taxonomically characterized and could not be differentiated from the human
      clinical reference strains of the species. Two avian strains were different in
      their phenotypic behaviors and constituted another genotypic subgroup. In
      general, all F. meningosepticum strains constituted a single species which was
      easily differentiated from biochemically similar species and phylogenetically
      closely related taxa.

PMID- 7814474
TI  - Rapid diagnosis of schistosomiasis by antigen detection in urine with a reagent
      strip.
AB  - For the rapid and simple diagnosis of schistosomiasis, a reagent strip assay for
      detection of circulating cathodic antigen (CCA) in urine was developed. The test
      was based on a previously developed sandwich enzyme-linked immunosorbent assay
      (ELISA) using a combination of two anti-CCA monoclonal antibodies. For the
      reagent strip assay, as the capture matrix, monoclonal antibody was coated onto a
      nitrocellulose membrane and mounted on polyvinyl chloride strips. Urine samples
      were then tested in an assay consisting of a combined incubation step of the
      urine sample and biotinylated detecting antibody followed by incubation in
      streptavidin peroxidase and a subsequent staining. The specificity and the
      sensitivity of the assay, as determined with urine samples of 61 uninfected
      controls and 67 Schistosoma mansoni-infected individuals, were 96.7 and 95.5%,
      respectively. The results of the reagent strip assay compared very well with
      microscopical parasitological diagnosis by the standard Kato-Katz method for the
      same individuals. The reagent strip test has a lower detection limit of 1 ng of
      CCA per ml and can be completed in 75 min. By the inclusion of two reference
      bands on the strips, standardized reading could be achieved. This reagent strip
      assay is a promising tool for qualitative diagnosis of S. mansoni infections in
      control programs.

PMID- 7814475
TI  - Genetic variation in Staphylococcus aureus coagulase genes: potential and limits
      for use as epidemiological marker.
AB  - To perform coagulase gene typing, the repeated units encoding hypervariable
      regions of the Staphylococcus aureus coagulase gene were amplified by the PCR
      technique; this was followed by AluI restriction enzyme digestion and analysis of
      restriction fragment length polymorphism (RFLP) patterns. In order to assess the
      discriminatory power of this typing method, 30 epidemiologically unrelated S.
      aureus strains which differed by their pulsed-field gel electrophoresis patterns
      were examined. Although 18 of the 30 strains had unique and unshared AluI RFLP
      patterns, there were only four observed patterns in the remaining 12 strains.
      This finding indicated that unrelated strains may share identical AluI RFLP
      patterns. To elucidate the degree of genetic variation in the C-terminus-encoding
      loci within the coagulase genes, the PCR products of these 12 strains were
      subjected to Taq polymerase-mediated sequencing. Sequence analysis confirmed the
      AluI recognition sites in each of the four RFLP groups and demonstrated that AluI
      appears to yield the highest RFLP in restriction enzyme analysis. By their DNA
      sequences the majority of strains sharing common AluI groups could be clearly
      differentiated from each other and revealed between 93.2 and 98.5% homology. When
      we determined the nucleotide sequences of two strains after six subcultivations
      no significant alterations were observed. Because the discriminatory power of the
      current coagulase gene typing method is not great enough to be used as the sole
      method to type S. aureus, additional techniques are necessary. Sequence analysis
      of the repeated unit-encoding region for the typing of S. aureus may be
      potentially useful as an alternative to other current molecular typing
      techniques.

PMID- 7814476
TI  - Ribosomal DNA internal transcribed spacer analysis supports synonomy of
      Scedosporium inflatum and Lomentospora prolificans.
AB  - Scedosporium inflatum is a dematiaceous opportunistic pathogen originally
      described by D. Malloch and I.F. Salkin (Mycotaxon 21:247-255, 1984). However, E.
      Gueho and G. S. De Hoog (J. Mycol. Med. 118:3-9, 1991) recently suggested
      reducing this mold to synonomy with Lomentospora prolificans on the basis of
      their similar morphological and molecular characteristics. We have investigated
      the ribosomal DNA internal transcribed spacers (ITS), i.e., ITS I and ITS II, of
      18 isolates, including these two fungi and a closely related pathogen,
      Scedosporium apiospermum, and its telemorph, Pseudallescheria boydii. Identical
      ITS restriction fragment length polymorphisms were found in eight isolates of S.
      inflatum and L. prolificans. These results support Gueho and De Hoog's proposal
      to combine S. inflatum and L. prolificans into the binomial Scedosporium
      prolificans. However, the ITS I sequence of S. apiospermum and the ITS
      restriction fragment length polymorphisms of S. apiospermum and P. boydii were
      found to be significantly different from those of S. inflatum and L. prolificans.
      The ITS restriction pattern differences may be valuable in clinical settings for
      distinguishing these fungi.

PMID- 7814477
TI  - Utility of complement fixation and microimmunofluorescence assays for detecting
      serologic responses in patients with clinically diagnosed psittacosis.
AB  - The serodiagnosis of human psittacosis was considerably improved by a
      microimmunofluorescence (MIF) assay that uses selected strains of Chlamydia
      psittaci, C. pneumoniae, and C. trachomatis as antigens. The 78 patients examined
      in the study were clinically diagnosed as having psittacosis on the basis of
      compatible clinical symptoms following exposure to sick birds. The conventional
      complement fixation (CF) test identified 36 patients, or 46% (36 of 78) of the
      total, as positive. Antibody responses to C. psittaci were demonstrated by the
      MIF test in all 36 CF-positive patients. The MIF test also detected antibody
      responses to C. psittaci in 12 patients (15% of the total) whose sera were
      negative or anticomplementary in the CF test. Seven patients, or 9% (7 of 78) of
      the total, were identified by the MIF test as having C. pneumoniae infections.
      About 30% of the study patients (23 of 78) showed no serologic evidence of either
      C. psittaci or C. pneumoniae infection by both the CF and the MIF tests. Four
      distinctive serologic reaction patterns were observed in the study patients.
      Recognition of these reaction patterns and judicious corroboration of serologic
      responses to the chlamydial species by the MIF test with epidemiologic and
      clinical information will increase the efficiency and accuracy of serodiagnosis
      for human psittacosis.

PMID- 7814478
TI  - Use of various genetic markers in differentiation of Mycobacterium bovis strains
      from animals and humans and for studying epidemiology of bovine tuberculosis.
AB  - One hundred fifty-three Mycobacterium bovis strains from cattle, various animal
      species from zoos and wild parks, and humans were analyzed for three different
      genetic markers for use in the epidemiology of bovine tuberculosis. M. bovis
      strains isolated from cattle were found to carry a single IS6110 element, whereas
      the majority of strains from other animals such as antelopes, monkeys, and seals
      harbored multiple IS6110 elements, suggesting that the reservoirs in cattle and
      wild animals are separated. Because the single IS6110 element in cattle strains
      is located at the same chromosomal position, strain differentiation by insertion
      sequence fingerprinting was hampered. Therefore, we investigated the usefulness
      of the direct repeat and polymorphic GC-rich repeat elements for strain
      differentiation. Both markers allowed sufficient strain discrimination for
      epidemiological purposes. Evidence is presented that in Argentina, most human M.
      bovis infections are due to transmission from cattle, whereas M. bovis infections
      among humans in the Netherlands are mainly contracted from animals other than
      cattle. Various outbreaks of M. bovis among animals and humans are described,
      including a small one which likely involved transmission from human to human.

PMID- 7814479
TI  - Identification of human herpesvirus 6 variants A and B by amplimer hybridization
      with variant-specific oligonucleotides and amplification with variant-specific
      primers.
AB  - Two distinct PCR-based procedures were evaluated for the detection and
      identification of human herpesvirus 6 (HHV-6) variants A and B in uncultured
      human samples. Variant-specific oligonucleotide hybridization (VSOH) is based on
      the amplification of two distinct regions of the HHV-6 genome, followed by
      hybridization of amplimers with variant-specific oligonucleotide probes. Variant
      specific primer PCR (VSPP) is based on the amplification of each variant by using
      variant-specific primers. The study of 10 well-characterized HHV-6 strains
      allowed us to demonstrate the high sensitivity and specificity of both methods.
      With variant mixtures, however, some limitations of VSOH were evidenced and VSPP
      was required to obtain unambiguous results. The combination of VSOH and VSPP was
      applied to the direct study of 300 peripheral blood mononuclear cell samples from
      French subjects. HHV-6 was detected in 15 samples: 11 corresponded to variant B,
      3 corresponded to variant A, and 1 corresponded to a mixture of both variants.

PMID- 7814480
TI  - Determination of parallelism and nonparallelism in bioassay dilution curves.
AB  - There is a lack of consensus among investigators who use a variety of immunoassay
      techniques (e.g., enzyme-linked immunosorbent assay [ELISA] and radioimmunoassay)
      regarding the protocols for describing and forming standard reference or
      calibration curves and interpolating serum antibody concentrations. This
      confounds the issue of detecting the presence or absence of parallelism between
      standard reference serum and serially diluted serum sample curves. These curves
      must be parallel to support the assumption that the antibody-binding
      characteristics are similar enough to allow the determination of antibody levels
      in the diluted serum sample. There is no universal and widely adopted strategy
      for assessing parallelism in bioassays, and without an assurance of parallelism,
      investigators are not able to calculate reliable estimates for antibody
      concentrations in serum samples. Furthermore, single-point (dilution) serum
      assays do not provide information related to parallelism and nonparallelism, and
      this, too, may lead to considerable error when calculating antibody
      concentrations. When assay methodology, technique, and precision improve to the
      extent that standard reference serum and serially diluted serum sample curves are
      fit with little error, standard analysis of variance techniques are overly
      sensitive to negligible departures from parallelism. We present a series of
      guidelines that compose a protocol for assessing parallelism between bioassay
      dilution curves that are applicable to data derived from ELISAs. These criteria
      should be applicable, with minor modifications, to most immunoassay experimental
      situations and, most importantly, are not dependent on the mathematical model
      used to form the standard reference curve. These guidelines have evolved in our
      laboratories over the past 4 years during the performance of thousands of ELISAs
      for antibodies to the capsular polysaccharides of Neisseria meningitidis groups A
      and C and Haemophilus influenzae type b.

PMID- 7814481
TI  - Development of interpretive criteria and quality control limits for broth
      microdilution and disk diffusion antimicrobial susceptibility testing of
      Streptococcus pneumoniae.
AB  - A five-center collaborative study was undertaken to develop quality control and
      specific interpretive criteria for susceptibility testing of Streptococcus
      pneumoniae against 12 antimicrobial agents. MICs were determined for 248
      pneumococcal clinical isolates (with an emphasis on resistant strains) by use of
      the National Committee for Clinical Laboratory Standards (NCCLS)-recommended
      broth microdilution procedure incorporating lysed horse blood-supplemented
      Mueller-Hinton broth. NCCLS disk diffusion testing was also performed for each
      isolate by using Mueller-Hinton sheep blood agar incubated in 5% CO2. Repetitive
      testing of S. pneumoniae ATCC 49619 with different sources and lots of media and
      disks allowed development of quality control ranges which encompassed
      approximately 95% of MIC and zone size values observed in the study. Good intra-
      and interlaboratory reproducibilities were seen with these testing methods and
      all of the drugs examined. On the basis of the results of this study, MIC
      interpretive criteria are proposed for 11 agents. Comparisons of MICs and disk
      diffusion zone sizes allowed disk diffusion zone size interpretive criteria to be
      proposed for five drugs and confirmed the use of the oxacillin disk test for
      prediction of penicillin susceptibility among pneumococci. Excessive numbers of
      minor-category interpretive errors precludes recommendation at this time of the
      disk diffusion method for testing of pneumococci against five of the drugs. Use
      of these proposed quality control and interpretive criteria should provide for
      reproducible test results and allow recognition of recently emerging resistance
      among pneumococcal clinical isolates.

PMID- 7814482
TI  - Nucleotide sequence analysis of enteropathogenic Escherichia coli (EPEC)
      adherence factor probe and development of PCR for rapid detection of EPEC
      harboring virulence plasmids.
AB  - The 1-kb BamHI-SalI fragment from plasmid pMAR2 termed the enteropathogenic
      Escherichia coli (EPEC) adherence factor (EAF) probe was cloned in pUC19 and
      pK18. The nucleotide sequence of this fragment was determined, and a set of
      primers was designed to amplify a 397-bp region associated with pMAR2 by PCR. An
      analysis of the whole EAF sequence with database libraries indicated no
      significant homology to any known genes. However, between bases 701 and 787 of
      the fragment, an 82.8% homology between the EAF and the insertion sequence IS630
      of Shigella sonnei exists. The results of PCR with primers of the EAF sequence
      demonstrated that all of the 151 EAF probe-positive EPEC strains with localized
      adherence to HEp-2 cells yielded positive EAF PCR results. In contrast, none of
      the 277 EAF probe-negative strains reacted to the EAF PCR. In addition, the PCR
      assay was successfully used to generate vector-free digoxigenin-labeled EAF
      fragments that gave valid results in colony blot hybridization assays. The EAF
      PCR appears to be a specific and efficient method for the detection of EPEC
      strains carrying the EAF plasmids.

PMID- 7814483
TI  - Sensitivities of radioimmunoprecipitation assay and PCR for detection of human T
      lymphotropic type II infection.
AB  - Five hundred forty-eight uncoagulated blood specimens from intravenous drug users
      infected with human T-lymphotropic virus type II (HTLV-II) were used to evaluate
      the sensitivities of the radioimmunoprecipitation assay (RIPA) and PCR for
      detecting HTLV-II-infected people. The sensitivities of both RIPA and PCR were
      found to be dependent on the HTLV-II antibody titer, as determined by the
      immunofluorescence assay. Neither of these recommended confirmatory methods was
      as sensitive for detecting weakly reactive HTLV-II specimens as the
      immunofluorescence assay, Western blotting (immunoblotting), or a modified
      licensed enzyme immunoassay. Use of RIPA and PCR to determine the reliabilities
      of other tests may sometimes give erroneous results.

PMID- 7814484
TI  - High doses of purified influenza A virus hemagglutinin significantly augment
      serum and nasal secretion antibody responses in healthy young adults.
AB  - The reactogenicity and immunogenicity of purified influenza virus hemagglutinin
      (HA) vaccines administered intramuscularly were evaluated in two placebo
      controlled clinical trials. A total of 139 healthy young adults were randomized
      to receive increasing doses of monovalent influenza A/Taiwan/1/86 (H1N1) virus HA
      (range, 0 to 405 micrograms per dose [study 1]). An additional 139 subjects were
      given increasing doses of a trivalent HA vaccine containing equal amounts of
      A/H1N1 virus, A/Shanghai/16/89 (H3N2) virus, and influenza B/Yamagata/16/88 virus
      HA (range, 0 to 135 micrograms of HA per strain, 0 to 405 micrograms per dose) or
      a standard dose of commercial influenza vaccine (study 2). Increasing doses of HA
      were associated with increasing frequencies of symptoms at the vaccination site
      early after vaccination, but all doses were well tolerated. Occurrence of
      systemic symptoms was unrelated to dose. Increasing the dose of HA resulted in
      increasingly higher postimmunization levels of serum hemagglutination inhibiting
      and neutralizing antibody levels versus influenza A/H1N1 virus in study 1 (P <
      0.05); these enhanced responses persisted for up to 6 months. Nasal secretory
      immunoglobulin A and G antibody responses were assessed 2 weeks after
      immunization with monovalent H1N1 virus HA; the frequencies of significant
      responses also increased in a dose-related fashion. Similar increases in serum
      antibody levels were noted for both A/H1N1 and A/H3N2 viruses in study 2. These
      data provide a basis for proceeding with the evaluation of high doses of purified
      HA in the elderly.

PMID- 7814485
TI  - Identification of an immunodominant 32-kilodalton membrane protein of Leishmania
      donovani infantum promastigotes suitable for specific diagnosis of Mediterranean
      visceral leishmaniasis.
AB  - Sera from 35 patients suffering from Mediterranean visceral leishmaniasis (caused
      by Leishmania donovani infantum) and 59 patients with various forms of cutaneous
      leishmaniasis prevalent in the sub-Mediterranean countries (caused by Leishmania
      major, L. donovani infantum, or Leishmania tropica) were tested by immunoblotting
      and enzyme-linked immunosorbent assay (ELISA) with both membrane and soluble
      antigens prepared from L. donovani infantum parasites. Control sera were from
      healthy children (n = 41), adults with nonleishmanial diseases (n = 40), and
      patients with Chagas' disease (n = 12). A P32 antigen present in the membrane
      preparation from L. donovani infantum parasites was recognized by 95% of serum
      specimens from patients with Mediterranean visceral leishmaniasis but not by
      serum specimens from patients with cutaneous leishmaniasis or sera from control
      individuals. An ELISA with electroeluted P32 antigen was found to have a
      specificity and sensitivity of 94% in the serodiagnosis of Mediterranean visceral
      leishmaniasis. Healthy children with asymptomatic Leishmania infection were
      seronegative for the P32 antigen by ELISA. These results suggest that antibodies
      to P32 antigen develop only in patients with visceral leishmaniasis and that the
      P32 ELISA may be useful in areas where the disease is endemic for discriminating
      between patients with this disease and those with other clinical conditions.

PMID- 7814486
TI  - Detection of resistance due to inducible beta-lactamase in Enterobacter aerogenes
      and Enterobacter cloacae.
AB  - Thirty-six of 36 strains of Enterobacter cloacae and E. aerogenes with inducible
      beta-lactamase developed resistance when cefoxitin (inducer) was added to
      cefuroxime disks. Constitutive beta-lactamase producers (n = 23) were all
      resistant to cefuroxime. Cefuroxime resistance correlated with the amount of
      induced or constitutive beta-lactamase. Cefuroxime was a better indicator of
      induced resistance than cefamandole, cefazolin, cephalothin, ceftriaxone,
      cefotaxime, ticarcillin with or without clavulanic acid, or cefotetan. Induction
      by addition of cefoxitin to disks occasionally reduced zone sizes but not enough
      to change interpretations for ceftazidime, ceftizoxime, aztreonam, cefoperazone
      with or without sulbactam, and piperacillin with or without tazobactam. Most
      enterobacters were resistant to cefmetazole. The cefoxitin inducer-cefuroxime
      indicator method can be used in routine clinical laboratories to detect latent
      resistance due to chromosomally mediated inducible beta-lactamase in
      enterobacters.

PMID- 7814487
TI  - Role of confirmatory PCRs in determining performance of Chlamydia Amplicor PCR
      with endocervical specimens from women with a low prevalence of infection.
AB  - The role of confirmatory PCR assays for determining the performance of Chlamydia
      Amplicor PCR for endocervical specimens from women with a low prevalence of
      infection was evaluated. An endocervical swab was collected from 770 women and
      tested by culture or direct fluorescent antibody (DFA) staining. A second swab
      was tested by Chlamydia Amplicor PCR (Roche Molecular Systems, Branchburg, N.J.).
      Discordant results were resolved by three confirmatory PCRs: one targeting the
      plasmid by using different primers and two directed to the major outer membrane
      protein (MOMP) gene. Of the 30 swabs that were positive by culture or DFA (3.9%),
      27 were positive by Amplicor PCR. An additional five swabs were positive by
      Amplicor PCR but negative by culture or DFA. Both plasmid and MOMP confirmatory
      PCRs identified the five culture-DFA negatives and the three Amplicor negatives
      as true positives. The three specimens originally classified as negative by
      Amplicor PCR were positive on repeat Amplicor testing. After resolution of the
      discordant results by confirmatory PCR testing, the sensitivity of the initial
      Amplicor PCR was 91.4% (32 of 35 specimens), changing to 100% after storage and
      repeat testing. The specificity of Amplicor PCR was 100% (735 of 735 specimens).
      Our results demonstrated that plasmid and MOMP confirmatory PCRs worked equally
      well in resolving false-positive and false-negative Amplicor PCR results. Some
      specimens may contain inhibitors of Amplicor PCR which may disappear with time.

PMID- 7814489
TI  - Distribution of Borrelia burgdorferi in host mice in Pennsylvania.
AB  - Host mice (Peromyscus leucopus and Peromyscus maniculatus) were sampled
      throughout the state of Pennsylvania to determine the geographical and ecological
      distribution of the Lyme disease spirochete Borrelia burgdorferi. All 67 counties
      of the state were sampled. A total of 1,619 mice were captured from a total of
      157 sites during the period 1990 to 1993 for an overall capture rate of 29.69%. A
      total of 112 (6.92%) isolations of B. burgdorferi were made. The distribution of
      isolations revealed the reason for the correlated distribution of human cases of
      Lyme disease in the state. Significantly more mice were captured and
      significantly more isolations were made from hemlock (Tsuga canadensis) habitat
      than from deciduous species forest. Nevertheless, high isolation rates from
      counties of the southeastern corner of the state illustrate well that hemlock
      habitat is not essential. Evidence suggests that in some areas, transmission
      between mice is occurring in some way other than through ticks as vectors. Host
      mice proved useful for determining the geographical and ecological distribution
      of B. burgdorferi.

PMID- 7814488
TI  - Comparative study of broth macrodilution and microdilution techniques for in
      vitro antifungal susceptibility testing of yeasts by using the National Committee
      for Clinical Laboratory Standards' proposed standard.
AB  - A comparative study of broth macro- and microdilution methods for susceptibility
      testing of fluconazole, itraconazole, flucytosine, and amphotericin B was
      conducted with 273 yeasts. The clinical isolates included 100 Candida albicans,
      28 Candida tropicalis, 25 Candida parapsilosis, 15 Candida lusitaniae, 15 Candida
      krusei, 50 Cryptococcus neoformans var. neoformans, 25 Torulopsis (Candida)
      glabrata, and 15 Trichosporon beigelii strains. Both methods were performed
      according to the National Committee for Clinical Laboratory Standards' (NCCLS)
      recommendations (document M27-P). For fluconazole, itraconazole, and flucytosine,
      the endpoint was the tube that showed 80% growth inhibition compared with the
      growth control for the macrodilution method and the well with slightly hazy
      turbidity (score 1) compared with the growth control for the microdilution
      method. For amphotericin B, the endpoint was the tube and/or well in which there
      was absence of growth. For the reference macrodilution method, the MICs were
      determined after 48 h of incubation for Candida spp., T. glabrata, and T.
      beigelii and after 72 h for C. neoformans var. neoformans. For the microdilution
      method, either the first-day MICs (24 h for all isolates other than C. neoformans
      and 48 h for C. neoformans var. neoformans) or the second-day MICs (48 and 72 h,
      respectively) were evaluated. The agreement within one doubling dilution of the
      macrodilution reference for all drugs was higher with the second-day MICs than
      with the first-day MICs for the microdilution test for most of the tested
      strains. General agreement was 92% for fluconazole, 85.7% for itraconazole, 98.3%
      for flucytosine, and 96.4% for amphotericin B. For C. neoformans var. neoformans
      and T. beigelii, the agreement of the first-day reading was higher than that of
      the second-day reading for fluconazole (94 versus 92%, respectively, for C.
      neoformans var. neoformans, and 86.7 versus 80%, respectively, for T. beigelii).
      Our studies indicate that the microdilution technique performed following the
      NCCLS guidelines with a second-day reading is a valid alternative method for
      testing fluconazole, itraconazole, flucytosine, and amphotericin B against these
      eight species of yeasts.

PMID- 7814490
TI  - Quantitative antibiogram typing using inhibition zone diameters compared with
      ribotyping for epidemiological typing of methicillin-resistant Staphylococcus
      aureus.
AB  - Antibiogram typing of methicillin-resistant Staphylococcus aureus with selected
      antibiotics was evaluated as a primary epidemiological typing tool and compared
      with ribotyping. Antibiograms were derived with the Kirby-Bauer disk diffusion
      method by using erythromycin, clindamycin, cotrimoxazole, gentamicin, and
      ciprofloxacin. For typing, antibiogram data were analyzed by similarity analysis
      of disk zone diameters (quantitative antibiogram typing). One hundred seventy-two
      isolates were typed. Reproducibility reached 98% for the quantitative antibiogram
      and 100% for ribotyping. With three selected restriction enzymes (EcoRV, HindIII,
      and KpnI), 40 epidemiologically unrelated isolates could be classified into 21
      ribotypes, whereas quantitative antibiogram typing classified these isolates into
      19 groups. To evaluate the discriminatory power of the methods, we calculated an
      index of discrimination from data obtained with these 40 isolates. This index
      takes into consideration both the number of types defined by the typing method
      and their relative frequencies. With both ribotyping and quantitative antibiogram
      typing, high discrimination indices (0.972 and 0.954, respectively) were
      obtained. When epidemiological links between patients (ward, period of
      hospitalization, and contacts between staff and patients) were compared with the
      results of ribotyping or the quantitative antibiogram typing method, it appeared
      that both methods were able to discriminate epidemiological clusters, with only a
      few discrepancies. In conclusion, quantitative antibiogram typing, although not
      necessarily based on genomic markers, is a simple method which enables a reliable
      workup of methicillin-resistant S. aureus epidemic when sophisticated molecular
      typing methods are not available.

PMID- 7814491
TI  - Hepatitis C virus (HCV) core serotypes in chronic HCV infection.
AB  - Recently, two distinct hepatitis C virus (HCV) serologic types have been
      identified on the basis of amino acid variations in the core region. The two
      serologic types can readily discriminate between genotypes I-II-V (serotype 1)
      and III-IV (serotype 2), according to the Okamoto classification. We compared HCV
      core serotyping with genotyping with sera from 363 anti-HCV-positive patients
      (309 HCV RNA positive by PCR) using a synthetic core peptide-based enzyme
      immunoassay and PCR amplification of core region sequences with type-specific
      primers, respectively. Serologic responses to HCV serotypes were successfully
      identified in 164 (45%) patients, of whom 153 were viremic. Eighty-nine patients
      had evidence of exposure to serotype 1: 8 of these were infected with genotype I,
      50 were infected with genotype II, 2 were infected with genotype III, 7 were
      infected with genotype V, 13 had infections with mixed genotypes, 3 were infected
      with an indeterminate genotype, and 6 were nonviremic. Seventy-four patients had
      been exposed to serotype 2: 64 were infected with genotype III, 3 were infected
      with mixed genotypes, 2 were infected with an indeterminate genotype, and 5 were
      nonviremic. The serum of one patient, infected with genotype III, showed
      reactivity to both serotypes. Comparative evaluation of HCV core region
      serotyping and genotyping with sera from 294 viremic patients infected with a
      known HCV genotype showed a remarkable concordance between HCV core region
      genotyping and serotyping, with only 2 apparently discordant serum samples (both
      from patients with genotype III infection) of 148 (1.4%) successfully serotyped
      samples. Serotype 1 infection was more frequently observed in patients with overt
      chronic liver disease and accounted for all successfully serotyped samples from
      intravenous drug abusers. In contrast, serotype 2 was more prevalent in subjects
      with biochemically silent HCV infection (alanine aminotransferase, < 45 U/liter),
      in agreement with previous findings at the molecular level. HCV core serologic
      typing is a simple, inexpensive, and highly reproducible assay that can be
      applied to more than 50% of viremic HCV antibody carriers prior to the use of
      more sophisticated molecular typing techniques. Moreover, it may be helpful in
      tracking transmissions routes, particularly for incorrectly stored samples in
      which the RNA has degraded or for subjects who have cleared the virus and
      therefore have only antibodies remaining to testify to a remote infection. The
      lack of recognition of the core sequence from residues 67 to 81, which contains a
      minor B-cell epitope used to detect type-specific immunoreactivity, may explain
      the negative serologic findings for half of the patients.

PMID- 7814492
TI  - Monitoring spread of Malassezia infections in a neonatal intensive care unit by
      PCR-mediated genetic typing.
AB  - Malassezia furfur and Malassezia pachydermatis were isolated from newborn
      children and incubators in a neonatal intensive care unit. To assess whether
      persistence or frequent import of the organisms was the cause of the elevated
      incidence, genetic typing of the strains was performed by PCR-mediated DNA
      fingerprinting. By using PCR primers aimed at repeat consensus motifs, six
      different genotypes could be detected in a collection of six M. furfur reference
      strains. In the case of 10 M. pachydermatis reference strains, nine different
      genotypes were detected by three different PCR assays. None of these assays could
      document genetic differences among the clinical isolates of either M. furfur or
      M. pachydermatis. On the basis of these results it is concluded that within the
      neonatal intensive care unit the longitudinal persistence of both an M. furfur
      and an M. pachydermatis strain has occurred and that Malassezia species can
      persist on incubator surfaces for prolonged periods of time. It can be concluded
      that PCR fingerprinting is a Malassezia typing procedure that is to be preferred
      over the analysis of chromosomal polymorphisms by pulsed-field gel
      electrophoresis in this genus.

PMID- 7814494
TI  - Ligase chain reaction to detect Chlamydia trachomatis infection of the cervix.
AB  - We performed a multicenter evaluation of ligase chain reaction (LCR) in the
      diagnosis of Chlamydia trachomatis infection of the cervix. This LCR provides an
      amplification of target sequences within the chlamydial cryptic plasmid. The LCR
      results were compared with those of isolation in cell culture. Discrepant (tissue
      culture-negative and LCR-positive) test results were resolved by the application
      of a direct immunofluorescent-antibody test to detect chlamydial elementary
      bodies and by the use of alternate DNA primers that targeted the chlamydial major
      outer membrane protein gene. A total of 234 of 2,132 specimens (10.9%) could be
      confirmed as containing C. trachomatis. Of these, 152 were detected by isolation
      in cell culture and 221 were detected by LCR. The corresponding sensitivities
      were 94% for LCR and 65% for cell culture. There was greater variability among
      study site results for cell culture sensitivity (52 to 92%) than for LCR
      sensitivity (87 to 98%). The specificity of each test was greater than 99.9%.
      Thus, LCR offers a highly sensitive nonculture method for detecting chlamydial
      infection of the cervix.

PMID- 7814493
TI  - Comparison of Western immunoblots and gene detection assays for identification of
      potentially enterotoxigenic isolates of Clostridium perfringens.
AB  - Clostridium perfringens enterotoxin (CPE) is an important sporulation-associated
      virulence factor in several illnesses of humans and domestic animals, including
      C. perfringens type A food poisoning. Therefore, the ability to determine the
      enterotoxigenicity of food or fecal C. perfringens isolates with simple, rapid
      assays should be helpful for epidemiologic investigations. In this study, Western
      immunoblotting (to detect CPE production in vitro) was compared with PCR assays
      and digoxigenin-labeled probe assays (to detect all or part of the cpe gene) as a
      method for determining the enterotoxigenicity of C. perfringens isolates. The cpe
      detection assays yielded reliable results with DNA purified from vegetative C.
      perfringens cultures, while Western immunoblots required in vitro sporulation of
      C. perfringens isolates to detect CPE production. Several cpe-positive C.
      perfringens isolates from diarrheic animals did not sporulate in vitro under
      commonly used sporulation-inducing conditions and consequently tested CPE
      negative. This result indicates that cpe gene detection and serologic CPE assays
      do not necessarily yield similar conclusions about the enterotoxigenicity of a C.
      perfringens isolate. Until further studies resolve whether these cpe-positive
      isolates which do not sporulate in vitro can or cannot sporulate and produce CPE
      in vivo, it may be preferable to use cpe detection assays for evaluating C.
      perfringens isolate enterotoxigenicity and thereby avoid potential false-negative
      conclusions which may occur with serologic assays.

PMID- 7814495
TI  - Nested PCR optimized for detection of Bordetella pertussis in clinical
      nasopharyngeal samples.
AB  - Several genes and sequences in Bordetella pertussis have been used as targets in
      diagnostic PCR assays. A previously developed single-step PCR assay for the
      detection of B. pertussis was based on an insertion sequence, IS480, that is
      present in about 70 to 80 copies in each genome. The diagnostic sensitivity,
      specificity, and reliability of this assay with aspirated and heat-treated
      samples from the nasopharynx of patients and their contacts was improved by the
      use of a nested PCR configuration. The nested PCR assay produced a 205-bp
      fragment with all of the 115 B. pertussis strains tested and was negative with
      all strains belonging to other Bordetella species (n = 44) as well as other
      bacteria commonly found in the upper respiratory tract (n = 115). The diagnostic
      value of the assay was verified by giving positive results for B. pertussis in
      all the 51 nasopharyngeal aspirates from culture-positive patients. The assay
      also detected 18 positive aspirates from a total of 196 culture-negative
      patients. A confirmatory cleavage of the 205-bp nested PCR product by MvaI gave
      in all cases two bands of 88 and 117 bp. In conclusion, this newly developed
      nested PCR assay was shown to be reasonably fast and uncomplicated, with an
      optimal sensitivity and a high degree of specificity for the diagnosis of B.
      pertussis in aspirated nasopharyngeal samples processed simply by heat treatment.
      The detection level in the nested PCR was about 10 bacteria per ml, or seven to
      eight insertion sequence copies per 10 microliters of boiled sample.

PMID- 7814496
TI  - Shigella sonnei strains isolated from U.S. summer students in Guadalajara,
      Mexico, from 1986 to 1992.
AB  - Plasmid DNA analysis and antibiotic susceptibilities were used to study strains
      of Shigella sonnei isolated from U.S. travelers to Guadalajara, Mexico, over a
      period of seven years (1986 to 1992). One hundred sixty-one isolates were
      analyzed. By the use of cluster analysis, eight different plasmid profiles were
      identified during this interval. At any point in time, three to seven different
      plasmid profiles were present in this population. The introduction of strains
      that carried a new plasmid with a molecular mass of 5.1 MDa was coincidental with
      an increase in isolation of S. sonnei in 1988. This new plasmid was present in
      87.5% of the isolates that were resistant to chloramphenicol. Shigellosis in
      Guadalajara follows a pattern of hyperendemic transmission with transient peaks
      of high-frequency isolation of S. sonnei. This pattern results from the
      concurrent presence of a heterogeneous group of strains as opposed to the
      widespread transmission of one or a few clones.

PMID- 7814497
TI  - Molecular epidemiology of Klebsiella pneumoniae strains that produce SHV-4 beta
      lactamase and which were isolated in 14 French hospitals.
AB  - Preliminary results suggested that the diffusion in France of the SHV-4 extended
      spectrum beta-lactamase was probably due to the spread of one single epidemic
      strain of Klebsiella pneumoniae. In this study, we tested various phenotypic and
      genotypic markers to compare K. pneumoniae strains producing this enzyme isolated
      in 14 French hospitals between 1987 and 1989. All of the strains were of the same
      capsule serotype, K25. Twelve of them were of the same biotype: weak urease
      activity and no sucrose fermentation. Among the six plasmid profiles observed,
      one accounted for eight strains. Large plasmids of 170 kb encoding SHV-4 beta
      lactamase were present in all strains of K. pneumoniae and could be transferred
      by conjugation with high frequency to Escherichia coli J53-2 or HB101 from all
      except one strain. Plasmid EcoRI restriction patterns suggested that these
      plasmids were closely related and similar to pUD18 encoding SHV-3 beta-lactamase,
      originally described in France and differing from SHV-4 by one amino acid
      substitution. Ribotyping with EcoRI and HindIII and genomic fingerprinting with
      XbaI by pulsed-field gel electrophoresis were concordant and suggested that 12 of
      the isolates recovered from the 14 hospitals were probably the same strain.
      Dissemination in France of the SHV-4 extended-spectrum beta-lactamase was thus
      essentially due to the diffusion of a single K. pneumoniae clone.

PMID- 7814498
TI  - Multicenter evaluation of a fully automated screening test, VIDAS HIV 1 + 2, for
      antibodies to human immunodeficiency virus types 1 and 2.
AB  - A multicenter study was done to evaluate the sensitivity, specificity, and
      efficiency of a new screening test for the simultaneous detection of human
      immunodeficiency virus type 1 and 2 (HIV-1 and HIV-2) antibodies. The VIDAS HIV 1
      + 2 (bioMerieux, Marcy l'Etoile, France) is a fully automated enzyme-linked
      fluorescent immunoassay that uses synthetic peptides from immunodominant regions
      of gp41 of HIV-1 and gp36 of HIV-2 as antigens. A total of 2,984 samples were
      evaluated with this system in six different laboratories, and the results were
      compared to those obtained with other enzyme-linked immunosorbent assays. The
      VIDAS HIV 1 + 2 assay showed a very good performance in terms of sensitivity
      (100%) and specificity (99.6%), requiring minimal manipulation and short
      incubation time (32 min) to give results similar to or better than those of the
      other enzyme-linked immunosorbent assays used for screening.

PMID- 7814499
TI  - Testing antimicrobial susceptibilities of adherent bacteria by a method that
      incorporates guidelines of the National Committee for Clinical Laboratory
      Standards.
AB  - Membrane filters (0.22-microns pore size) were colonized with 10(4) CFU of
      logarithmic-phase bacteria per filter under laminar flow conditions in a Modified
      Robbins Device. Colonized filters were then placed upon agar dilution plates for
      MIC determinations. Subsequently, filters were transferred to control plates and
      incubated to obtain MBCs.

PMID- 7814500
TI  - Bacteremia caused by a novel Bordetella species, "B. hinzii".
AB  - Bordetella spp. cause respiratory tract diseases in warm-blooded animals. Only
      Bordetella bronchiseptica has been reported to cause bacteremia in humans, and
      this rare infection usually occurs with pneumonia in immunocompromised patients.
      We describe "Bordetella hinzii" bacteremia in an AIDS patient without a
      respiratory illness. Combining biochemical phenotyping with fatty acid analysis
      permitted preliminary identification of this previously undescribed pathogen;
      identity was confirmed by DNA-DNA hybridization. This report extends the spectrum
      of human infections caused by the bordetellae.

PMID- 7814501
TI  - Pneumococcal resistance to antimicrobial agents in the province of Quebec,
      Canada.
AB  - The serogroup/serotypes (SGTs) and antimicrobial susceptibilities to 10
      antimicrobial agents of 110 clinical strains of Streptococcus pneumoniae were
      determined. Strains intermediately resistant or highly resistant to penicillin G
      (80 of 110) belonged predominantly to SGTs 23 (45.0%), 19 (13.7%), 6 (10.0%), 9
      (6.2%), and 14 (3.7%). The MICs of all cephalosporins, tetracycline, trimethoprim
      sulfamethoxazole, and chloramphenicol increased along with the MICs of penicillin
      G. However, erythromycin resistance and clindamycin resistance were observed more
      frequently among the intermediately penicillin-resistant strains. Multiple
      resistance was observed for 32 strains, of which 25 were highly resistant to
      penicillin G and belong to SGT 23F. All strains were susceptible to vancomycin.

PMID- 7814502
TI  - Optimum recovery of Mycobacterium avium complex from blood specimens of human
      immunodeficiency virus-positive patients by using small volumes of isolator
      concentrate inoculated into BACTEC 12B bottles.
AB  - Recovery of Mycobacterium avium complex organisms from 412 lysis-centrifugation
      (Isolator) concentrates of blood specimens obtained from human immunodeficiency
      virus-positive individuals was attempted with the following media (and Isolator
      concentrate inoculum volumes): BACTEC 12B broth (0.2 and 1.0 ml), Lowenstein
      Jensen slants (0.1 ml), and Middlebrook 7H10/11 agar (0.1 ml). A total of 42 M.
      avium complex isolates were recovered. The highest rates of recovery and shortest
      detection times were noted with BACTEC 12B bottles inoculated with 0.2 ml of
      Isolator concentrate. Middlebrook agar was superior to Lowenstein-Jensen slants.
      Fluorochrome acid-fast smears performed directly upon Isolator concentrates were
      of no utility.

PMID- 7814503
TI  - Plasmodium vivax ookinetes in human peripheral blood.
AB  - Microscopic examination of a peripheral blood smear revealed ookinetes of
      Plasmodium vivax. This unusual finding was probably due to an excessive delay
      between blood collection and smear preparation. Ookinete formation normally
      occurs in the mosquito gut. When seen in blood smears, it can cause confusion and
      misidentification of the parasite.

PMID- 7814504
TI  - Comparison of heparin and EDTA transport tubes for detection of cytomegalovirus
      in leukocytes by shell vial assay, pp65 antigenemia assay, and PCR.
AB  - The anticoagulants heparin and EDTA were compared for inhibitory effects on the
      detection of cytomegalovirus from washed leukocytes in specimen transport tubes.
      Evaluation was made by the centrifugation/shell vial culture technique, the pp65
      antigenemia assay, and PCR. For each assay, the results with heparin and EDTA
      were equivalent.

PMID- 7814505
TI  - Imipenem stability in a predried susceptibility panel.
AB  - We performed a 15-month study using 11 clinical strains and 1 control strain
      (ATCC 27853) of Pseudomonas aeruginosa to determine whether changes in the
      manufacturing process of Sensititre predried panels result in a reliable test of
      susceptibility to imipenem. MIC and breakpoint susceptibility results remained
      stable during the manufacturer's recommended shelf life of 18 months and compared
      well with standard agar disk diffusion and broth macrodilution results. Imipenem
      concentrations measured by high-pressure liquid chromatography were acceptable
      through 15 months but declined in the breakpoint panels by approximately 50% at
      18 months. Between 9 months and panel expiration, 13 of 141 (9%) of the MIC panel
      packages had moisture entry, as indicated by pink desiccants, with a resultant
      loss of imipenem activity of 32 to 100%. It appears that the new manufacturing
      process produces MIC panels that are reliable for imipenem susceptibility testing
      until the labeled expiration date, provided that packages containing pink
      desiccants are not used.

PMID- 7814506
TI  - Evaluation of BBL crystal MRSA ID system.
AB  - The BBL Crystal system (Becton Dickinson Microbiology Systems, Cockeysville, Md.)
      was evaluated for its accuracy in identifying oxacillin resistance in
      Staphylococcus aureus by testing of mec-specific-gene-positive and -negative
      isolates. Although the manufacturer makes no claim for use of the product for
      testing of staphylococci other than S. aureus, the product's potential utility in
      detecting oxacillin resistance in isolates of mec gene-positive and -negative
      Staphylococcus epidermidis was also explored. All mec gene-negative staphylococci
      yielded a negative MRSA ID test reaction. There was a close correlation between
      mec gene positivity and a positive reaction in the methicillin-resistant S.
      aureus identification system with 63 of 69 (91%) stock isolates of S. aureus
      yielding a positive result in 4 h, 66 of 69 (95%) yielding a positive result in 5
      h, and 68 of 69 (99%) yielding a positive result in 6 h. The corresponding
      percentage agreements at 4, 5, and 6 h for mec gene-positive stock isolates of S.
      epidermidis were 87, 91, and 96%, respectively.

PMID- 7814507
TI  - Diagnosis of enteroviral meningitis by using PCR with a colorimetric microwell
      detection assay.
AB  - A 5-h, user-friendly PCR assay for the diagnosis of enteroviral meningitis was
      developed. Reverse transcription and amplification were performed in a one-step
      reaction using rTth polymerase. Carryover contamination was prevented with dUTP
      and uracil N-glycosylate. Detection was performed colorimetrically on a microwell
      titer plate. Sensitivity, specificity, positive predictive value, and negative
      predictive value were 94.7, 97.4, 94.7, and 97.4%, respectively.

PMID- 7814508
TI  - Detection of Campylobacter upsaliensis from a blood culture by using the
      BacT/Alert system.
AB  - Campylobacter upsaliensis was isolated from the blood of a 60-year-old female
      with hairy cell leukemia. This spiral-shaped organism was detected in the aerobic
      BacT/Alert bottle (Organon Teknika, Durham, N.C.) by acridine orange staining and
      was recovered only on chocolate agar in a microaerophilic atmosphere at 35
      degrees C.

PMID- 7814509
TI  - Reverse transcriptase-PCR assay for detection of hog cholera virus.
AB  - A reverse transcriptase-PCR strategy was developed for the detection of hog
      cholera virus. Hog cholera virus template was amplified from tissue culture
      fluids and from tissues and blood of infected pigs, but not from samples
      containing other pestiviruses. Restriction endonuclease analysis identified
      samples as historic or recent isolates.

PMID- 7814510
TI  - Evaluation of a new reagent for anti-cytomegalovirus and anti-Epstein-Barr virus
      immunoglobulin G.
AB  - The Enzygnost alpha method was tested against the complement fixation test and
      anti-VCA immunofluorescence to determine the respective titers of anti
      cytomegalovirus and anti-Epstein-Barr virus immunoglobulin G antibodies. For
      cytomegalovirus, the Enzygnost results showed 97.99% agreement with the readings
      obtained by the alternative method, with 100% sensitivity and 93.7% specificity.
      For Epstein-Barr virus, Enzygnost showed 97.71% agreement, 100% sensitivity, and
      91.11% specificity.

PMID- 7814511
TI  - Equine rotaviruses with G14 serotype specificity circulate among venezuelan
      horses.
AB  - Two group A rotavirus strains isolated from diarrheic foals in Venezuela were
      classified as belonging to G14 serotype by cross-neutralization tests and on the
      basis of the homology of the sequenced VP7 gene. This report confirms that
      rotavirus strains of G14 serotype specificity circulate among equine populations.

PMID- 7814512
TI  - Comparison of sample preparation methods for detection of Chlamydia pneumoniae in
      bronchoalveolar lavage fluid by PCR.
AB  - Amplification inhibitors can lead to false-negative results for PCR. In order to
      evaluate the reliability of PCR for the detection of Chlamydia pneumoniae, the
      presence of PCR inhibitors in 75 bronchoalveolar lavage specimens was assessed
      after treatment by various sample preparation methods. Specimens were collected
      from patients with acute respiratory infections, including four cases of proven
      C. pneumoniae infection. Substances inhibitory to the amplification of chlamydial
      DNA continued to be present in 12% of the samples treated according to the
      commonly used single-step proteinase K digestion and in 31% of the samples
      processed by heat treatment. However, the complexing of DNA-contaminating
      proteins and polysaccharides from digested specimens to cetyltrimethylammonium
      bromide (CTAB) followed by DNA extraction efficiently removed inhibitors from all
      experimental samples and provided subsequent identification of all positive
      clinical samples by PCR. The CTAB method and proteinase K treatment had
      comparable detection limits of approximately 0.01 inclusion-forming units. CTAB
      based DNA purification of respiratory specimens is recommended to increase the
      diagnostic sensitivity of PCR and confidence in negative results.

PMID- 7814513
TI  - Discriminatory genomic fingerprinting of Legionella pneumophila by pulsed-field
      electrophoresis.
AB  - Eight strains of Legionella pneumophila were used to optimize cleavage of DNA
      with BssHII, SalI, or SpeI and separation by pulsed-field electrophoresis.
      Isolates from a community outbreak involving a contaminated hot tub were
      genomically identical. Cleavage patterns were distinctly different for unrelated
      environmental and nosocomial strains from a single hospital.

PMID- 7814514
TI  - Survey of rotavirus G and P types associated with human gastroenteritis in Sao
      Paulo, Brazil, from 1986 to 1992.
AB  - Rotavirus strains causing gastroenteritis in Brazilian children were
      characterized by PCR-based typing assays. In addition to strains bearing the
      major human G and P types, large numbers of strains bearing P3 (M37-like), P6
      (HCR3-like), untypeable P and G types, and complex mixtures of P and G types not
      previously recognized were present in the community.

PMID- 7814515
TI  - Clonal outbreaks of extended-spectrum beta-lactamase-producing strains of
      Klebsiella pneumoniae demonstrated by antibiotic susceptibility testing, beta
      lactamase typing, and multilocus enzyme electrophoresis.
AB  - Nineteen extended-spectrum beta-lactamase (ESBla)-producing Klebsiella pneumoniae
      isolates from Rouen Hospital were investigated for their implication in
      nosocomial outbreaks: in addition to antibiotic susceptibility testing, the
      ESBlas were characterized by isoelectric focusing, and the genetic relationships
      between the strains were analyzed by multilocus enzyme electrophoresis using a
      combined polyacrylamide electrophoresis-electrophoretic transfer technique. Four
      isoelectric focusing beta-lactamase patterns and 11 enzyme electrophoretic types
      (ETs) among the strains tested were described. Three strains isolated in the same
      neurological unit over a 7-day period exhibited an SHV 3 beta-lactamase (pI 7.0)
      and were assigned to a common ET. Three of five strains isolated from patients in
      a rehabilitation center over a 6-week period harbored an SHV 4 beta-lactamase (pI
      7.8) and exhibited the same ET. These results differentiate nosocomial
      transmission from sporadic cases and provide evidence that multilocus enzyme
      electrophoresis is a potential tool for studying genetic relationships between
      strains harboring a common ESBla.

PMID- 7814516
TI  - Use of API NH system for identification of Moraxella catarrhalis.

PMID- 7814517
TI  - Fecal lactoferrin as a marker of fecal leukocytes.

PMID- 7814518
TI  - Use of selective media for isolating Corynebacterium urealyticum from urine
      specimens.

PMID- 7814519
TI  - Proper combination for Alcaligenes xylosoxidans subsp. xylosoxidans.

PMID- 7814520
TI  - Coamplified positive control detects inhibition of polymerase chain reactions.

PMID- 7814522
TI  - Demonstration of circulating group B streptococcal immune complexes in neonates
      with meningitis.
AB  - Group B streptococci are the major cause of sepsis and fatal shock in neonates in
      the United States. Although a number of clinical features have been associated
      with enhanced severity of disease, the role of soluble immune complex formation
      in group B streptococcal infection has not been evaluated. We determined the
      frequency with which circulating immune complexes occurred in 16 infants with
      nonfatal type III, group B streptococcal meningitis, using an immunoglobulin
      specific C1q enzyme immunoassay. Ten healthy, age-matched infants served as a
      control group. Elevated levels of immunoglobulin M (IgM)-containing immune
      complexes were present in the sera of four (25%) patients with group B
      streptococcal meningitis. Group B antigen was detected in precipitated IgM immune
      complexes from each of these four infants by competitive enzyme-linked
      immunosorbent assay. In addition, IgG-containing immune complexes were present in
      56% of sick and 60% of control infants. Group B antigen was demonstrated in the
      serum of a sick neonate containing only IgG immune complexes but not in controls.
      Our findings indicate that a subset of infants with type III, group B
      streptococcal meningitis develop IgM immune complexes containing group B-specific
      antigen, and these may persist for up to 3 months in some patients.

PMID- 7814523
TI  - Evaluation of two commercial human T-cell lymphotropic virus western blot
      (immunoblot) kits with problem specimens.
AB  - We evaluated two commercial human T-cell lymphotropic virus (HTLV) Western blot
      (WB; immunoblot) kits, Cambridge Biotech Corp. (CBC) and Diagnostic Biotechnology
      Ltd. (DBL). Both methods employ HTLV type I (HTLV-I) viral lysate and rgp21. The
      DBL WB kit also distinguishes between HTLV-I and HTLV-II antibodies, using an
      HTLV-I-specific and an HTLV-II-specific recombinant. Fifty weakly reactive HTLV
      II-positive plasma specimens which were falsely negative with the Abbott enzyme
      immunoassay (EIA) and 50 Ortho EIA false-positive samples were selected to
      determine sensitivity and specificity. The sensitivities of the CBC and the DBL
      WB kits were 90 and 68%, respectively. All positive samples reacted with rgp21 in
      both kits, but some did not display core bands. Five samples were typed as HTLV-I
      and four were typed as dual infection by the DBL WB kit. The specificities of the
      CBC and DBL kits were 48 and 70%, respectively. The most prevalent WB reaction
      with the negative samples was with the core protein, p19, followed by p24 and p28
      for CBC and rgp21 and p28 for DBL. DBL had two false-positive interpretations,
      and CBC had none, rgp21 was the most sensitive antigen in both kits for the
      weakly reactive HTLV-II samples. If all samples not reacting with this protein
      were interpreted as WB negative, regardless of other bands, the specificity would
      improve to 90% for CBC and 86% for DBL.

PMID- 7814524
TI  - Clinical comparison of isolator and thiol broth with ESP aerobic and anaerobic
      bottles for recovery of pathogens from blood.
AB  - The recovery of pathogens and the speed of their detection were determined for
      our conventional blood culture system (an Isolator [Wampole] and a 100-ml Thiol
      bottle [Difco]) compared with automated ESP aerobic and anaerobic bottles (80 ml
      each; Difco). Each of the four culture devices was inoculated with approximately
      10 ml of blood from symptomatic patients weighing more than 80 lb (ca. 36 kg).
      From 7,070 sets of cultures for 2,841 patients, 607 clinically significant
      isolates were recovered: 456 (75.1%) from the Isolator, 353 (58.2%) from Thiol,
      377 (62.1%) from ESP aerobic bottles, and 346 (57.0%) from ESP anaerobic bottles.
      Of the 607 isolates, 149 (24.5%) were detected only with the conventional system
      (Isolator and/or Thiol), and 65 (10.7%) were detected only with the ESP two
      bottle system (P < 0.001). Our conventional system allowed for detection of
      significantly more isolates of members of the family Enterobacteriaceae (P <
      0.001), Staphylococcus aureus (P < 0.01), Staphylococcus spp. (coagulase
      negative) (P < 0.01), and Enterococcus spp. (P < 0.05), and ESP facilitated
      detection of significantly more isolates of S. pneumoniae (P < 0.01). When all
      four devices in a culture set were positive for the same isolate, no microbial
      species or group was detected significantly earlier ( > or = 24 h) by either
      blood culture system. The Isolator contamination rate (4.8%) was > or = 6 times
      the rate for any of the bottles. Of pathogens detected by the Isolator, 50% were
      recovered in counts of < or = 1.0 CFU/ml and 18% were recovered only as a single
      colony. The ESP system offered an automated, less labor-intensive blood culture
      system for which routine subcultures were not required, but the important
      considerations of culturing large volumes of blood and of obtaining at least two
      sets from each patient in our population were reemphasized.

PMID- 7814525
TI  - Evaluation of RapiDEC Staph for identification of Staphylococcus aureus,
      Staphylococcus epidermidis, and Staphylococcus saprophyticus.
AB  - RapiDEC Staph is a test for presumptive identification of the principal human
      staphylococcal species, Staphylococcus aureus, S. epidermidis, and S.
      saprophyticus. The test includes control and test cupules for fluorogenic
      detection of coagulase and chromogenic substrates for alkaline phosphatase and
      beta-galactosidase. These tests identify S. aureus, S. epidermidis, and S.
      saprophyticus, respectively. Positive results with both chromogenic substrates
      provide a presumptive identification of S. xylosus or S. intermedius (S. xylosus
      S. intermedius). Test cupules are inoculated with an organism suspension, and
      reactions are read after a 2-h incubation. RapiDEC-Staph was evaluated with 303
      clinical and stock staphylococcal strains. Identifications were compared with
      those obtained by the tube coagulase test, a latex slide coagulase test
      (StaphAUREX), another commercial identification system (Staph-TRAC), and
      additional conventional tests. RapiDEC-Staph correctly identified 100% of 130 S.
      aureus strains, 70.3% of 74 S. epidermidis strains, and 81.3% of 32 S.
      saprophyticus strains. Four of five S. xylosus isolates were called S. xylosus-S.
      intermedius. Unidentified S. epidermidis and S. saprophyticus strains were called
      "Staphylococcus spp." Among the 62 other coagulase-negative staphylococci, 4 were
      misidentified as S. epidermidis and 7 were misidentified as S. saprophyticus.
      While the sensitivity and specificity of the fluorogenic coagulase test for S.
      aureus were 100%, failure to detect alkaline phosphatase activity in several S.
      epidermidis isolates resulted in fewer correct identifications by the RapiDEC
      Staph test for this species.

PMID- 7814526
TI  - Application of typing by pulsed-field gel electrophoresis to the study of
      Clostridium difficile in a neonatal intensive care unit.
AB  - Pulsed-field gel electrophoresis (PFGE) analysis of restriction pattern
      polymorphism was applied to type Clostridium difficile isolated from neonates
      hospitalized in a neonatal intensive care unit, and the results were compared
      with those of immunoblot analysis. C. difficile was isolated from fecal specimens
      of 41 (61%) of 67 neonates during a 5-month investigation. All of these neonates
      were asymptomatic. Fifty-five C. difficile isolates from 32 patients were
      analyzed by PFGE after digestion with SmaI and SacII endonucleases and by
      immunoblotting with 10 different antisera. Fifty-three of 55 isolates from 30
      patients were identical by PFGE analysis after SmaI and SacII digestion and
      immunoblot analysis. Two isolates were different from each other and from the
      epidemic group by both PFGE and immunoblot analysis. All 53 epidemic isolates
      were nontoxigenic, while the two remaining isolates were toxigenic. These results
      suggest that nosocomial spread of nontoxigenic C. difficile infection in the
      neonatal intensive care unit and suggest that both PFGE and immunoblot are
      powerful typing tools for the epidemiological study of C. difficile.

PMID- 7814527
TI  - Reverse transcription-PCR detection of LaCrosse virus in mosquitoes and
      comparison with enzyme immunoassay and virus isolation.
AB  - A reverse transcription-PCR (RT-PCR) assay was developed and compared with enzyme
      immunoassay (EIA) and virus isolation for detecting LaCrosse virus (LAC) in
      mosquito pools. All three techniques were able to detect a single LAC-infected
      mosquito in a pool of 99 negative mosquitoes. Virus isolation was the most
      sensitive of the three techniques; it was possible to isolate virus immediately
      following intrathoracic inoculation of mosquitoes. RT-PCR was second in
      sensitivity; LAC RNA was detected 1 day postinfection. EIA detected LAC antigen 2
      days postinfection. Additionally, RT-PCR and EIA were able to detect LAC RNA and
      protein, respectively, from mosquito samples which were subjected to seven freeze
      thaw cycles, and RT-PCR was able to detect LAC RNA from mosquito samples which
      remained at room temperature for up to 7 days.

PMID- 7814528
TI  - Spread and maintenance of a dominant methicillin-resistant Staphylococcus aureus
      (MRSA) clone during an outbreak of MRSA disease in a Spanish hospital.
AB  - It was not until November 1989 that the 1,000-bed University-affiliated Hospital
      de Bellvitge "Princeps d'Espanya" in Barcelona first acquired methicillin
      resistant Staphylococcus aureus (MRSA). Since that time, the outbreak of MRSA
      disease has continued. We have analyzed by genomic DNA fingerprinting 189 MRSA
      isolates collected between late 1989 and the end of 1993. The isolates include
      both invasive and colonizing strains as well as isolates from health-care workers
      and environmental sources. In addition, 52 clinical isolates of methicillin
      susceptible S. aureus (MSSA) collected in the same hospital were also analyzed.
      Isolates were classified into clonal types on the basis of molecular typing
      techniques. A single MRSA clone (I::B::a) belonging to ClaI type I, pulsed-field
      gel electrophoretic pattern B, and Tn554 pattern a was responsible for the great
      majority of infections (73% of blood cultures and 79% of specimens from other
      clinical sources). This clone appeared at the very beginning of the outbreak,
      spread throughout the hospital wards, and was also carried by inpatients and
      health-care workers and on environmental surfaces. In contrast, no dominant
      lineage was apparent among MSSA isolates (33 distinct pulsed-field gel
      electrophoretic patterns among 52 isolates). Two MSSA isolates seem to have
      originated from the dominant clone by deletion of the mecA gene and some
      additional DNA. In several isolates, different mecA polymorphs were present in
      identical chromosomal backgrounds or cells with distinct chromosomal backgrounds
      carried the same mecA polymorph, suggesting horizontal transfer of the mecA gene.

PMID- 7814529
TI  - Comparison of methods for detection of hepatitis B virus DNA.
AB  - We compared the performance of four assays for detection of hepatitis B virus
      (HBV) DNA: the PCR; the branched DNA hybridization assay (Chiron); and two
      hybridization assays that use liquid hybridization (Abbott) or direct membrane
      hybridization (MH). Testing 109 random hepatitis B surface antigen-positive
      patient samples, the percentages found to be HBV DNA positive among 30 hepatitis
      B e antigen (HBeAg)-positive samples and 79 HBeAg-negative samples were as
      follows: PCR, 100 and 90%; Chiron, 73 and 25%; Abbott, 67 and 13%; and MH, 40 and
      8%. In six hepatitis B surface antigen-positive, HBeAg-negative samples, all
      three hybridization assays detected HBV DNA. Testing dilutions prepared from the
      Eurohep HBV DNA standards, the detection limits of the assays appeared to be the
      following: PCR, 2.5 x 10(2) HBV genomes per ml; Chiron, 2.5 x 10(6) genomes per
      ml; and Abbott and MH, 2.5 x 10(7) genomes per ml. HBV DNA levels in the dilution
      series, as reported by the Chiron and MH assays, were, on average, 2 times higher
      than calculated; the Abbott results were, on average, 19 times lower than
      calculated. We concluded that high levels of HBV DNA and the presence of HBeAg do
      not necessarily coincide, that the application of hybridization assays is limited
      to the monitoring of relatively high levels of HBV DNA, and that further
      standardization of quantitative HBV DNA assays is necessary to facilitate
      comparison of HBV DNA levels.

PMID- 7814531
TI  - Comparison of broth macrodilution, broth microdilution, and E test antifungal
      susceptibility tests for fluconazole.
AB  - A comparison of the E test, the broth microdilution test, and the reference broth
      macrodilution susceptibility test of the National Committee for Clinical
      Laboratory Standards for fluconazole susceptibility testing was performed with
      238 clinical isolates of Candida species and Torulopsis (Candida) glabrata. An
      80% inhibition endpoint MIC was determined by the reference broth macrodilution
      method after 48 h of incubation. The MICs obtained by the two study methods were
      read after 24 and 48 h of incubation. Overall, excellent agreement within 2
      doubling dilutions was obtained between the broth microdilution and the broth
      macrodilution methods for the combined results for all species at both 24 h (93%)
      and 48 h (94%). The correlation of 24-h MIC endpoints between the E test and the
      broth macrodilution methods was 37% for T. glabrata, 56% for Candida tropicalis,
      93% for Candida albicans, and 90% for other Candida species. The percent
      agreement at 48 h ranged from 34% for T. glabrata to 97% for Candida species
      other than C. albicans and C. tropicalis. These initial results support the
      further evaluation of the E test as an alternative method for fluconazole
      susceptibility testing of Candida species.

PMID- 7814532
TI  - Controlled evaluation of 5 versus 10 milliliters of blood cultured in aerobic
      BacT/Alert blood culture bottles.
AB  - Bottles developed for use in the BacT/Alert automated blood culture system
      (Organon Teknika Corp., Durham, N.C.) can accept up to 10 ml of blood without
      falling below a 1:5 ratio of blood to broth. We compared the yield and speed of
      detection of microorganisms in 13,128 adequately filled, paired, aerobic bottles
      inoculated with 5 versus 10 ml of blood at three university hospitals. A total of
      798 microorganisms causing sepsis grew in one or both bottles. The overall
      recovery of microorganisms from 10-ml samples exceeded that from 5-ml samples (P
      < 0.001); the increased yield attributed to the additional 5 ml in the samples
      was 7.2%. The increased yield from 10-ml inocula was most marked for Escherichia
      coli (P < 0.01) and other members of the family Enterobacteriaceae (P < 0.001).
      Ten-milliliter samples did not yield more gram-positive bacteria, nonfermentative
      gram-negative rods, or yeasts. When both bottles were positive, the bottles
      inoculated with 10 ml of blood showed growth sooner (P < 0.001). Earlier
      detection with 10-ml inocula was especially notable for coagulase-negative
      staphylococci (P < 0.001), streptococci (P < 0.001), E. coli (P < 0.025), and
      other members of the family Enterobacteriaceae (P < 0.025). We conclude that an
      increase in the volume of blood inoculated into BacT/Alert aerobic blood culture
      bottles from 5 to 10 ml will increase the overall yield and the speed of
      detection of clinically important blood pathogens.

PMID- 7814530
TI  - Emergence of fluconazole-resistant strains of Candida albicans in patients with
      recurrent oropharyngeal candidosis and human immunodeficiency virus infection.
AB  - After repeated use of fluconazole for therapy of oropharyngeal candidosis, the
      emergence of in vitro fluconazole-resistant Candida albicans isolates (MIC, > or
      = 25 micrograms/ml) together with oral candidosis unresponsive to oral dosages of
      up to 400 mg of fluconazole were observed in patients with human immunodeficiency
      virus (HIV) infection. Antifungal susceptibility testing was done by broth
      microdilution and agar dilution techniques on C. albicans isolates recovered from
      a cohort of patients with symptomatic HIV infection who were treated repeatedly
      with fluconazole for oropharyngeal candidosis. In vitro findings did show a
      gradual increase in the MICs for C. albicans isolates recovered from selected
      patients with repeated episodes of oropharyngeal candidosis. Primary resistance
      of C. albicans to fluconazole was not seen. Cross-resistance in vitro occurred
      between fluconazole and other azoles (ketoconazole, itraconazole), but to a
      lesser extent. The results of the study suggest that the development of clinical
      resistance to fluconazole could be clearly correlated to in vitro resistance to
      fluconazole. Itraconazole may still serve as an effective antifungal agent in
      patients with HIV infection and oropharyngeal candidosis nonresponsive to
      fluconazole.

PMID- 7814533
TI  - Western immunoblot analysis of Ehrlichia chaffeensis, E. canis, or E. ewingii
      infections in dogs and humans.
AB  - Ehrlichia chaffeensis, E. canis, and E. ewingii are genetically closely related,
      as determined by 16S rRNA gene base sequence comparison, but they exhibit
      biologic differences. E. chaffeensis is the etiologic agent of human
      ehrlichiosis. E. canis and E. ewingii cause two distinctly different forms of
      canine ehrlichiosis and infect different types of leukocytes, monocytes and
      granulocytes, respectively. E. chaffeensis can also infect dogs. In the study,
      Western immunoblot analysis of sera from dogs inoculated with E. chaffeensis, E.
      canis, or E. ewingii was performed to determine antigenic specificity and the
      intensities of the reactions to purified E. chaffeensis and E. canis antigens. At
      2 to 3 weeks postexposure, antisera from four dogs inoculated with E. chaffeensis
      reacted with 64-, 47-, 31-, and 29-kDa proteins of E. chaffeensis but reacted
      poorly with E. canis antigen. In contrast, at 2 to 3 weeks postexposure, antisera
      from four E. canis-inoculated dogs reacted strongly with the 30-kDa major antigen
      of E. canis but reacted poorly with proteins from E. chaffeensis. At 4 weeks
      postexposure, the sera from three E. ewingii-inoculated dogs showed weak binding
      to 64- and 47-kDa proteins of both E. chaffeensis and E. canis. Convalescent
      phase sera from human ehrlichiosis patients and sera from dogs chronically
      infected with E. ewingii strongly reacted with similar sets of proteins of E.
      chaffeensis and E. canis with similar intensities. However, sera from dogs
      chronically infected with E. canis reacted more strongly with a greater number of
      E. canis proteins than with E. chaffeensis proteins. The protein specificity
      described in the report suggests that dogs with E. canis infections can be
      distinguished from E. chaffeensis-infected animals by Western immunoblot analysis
      with both E. canis and E. chaffeensis antigens.

PMID- 7814534
TI  - Efficacy of microbial identification system for epidemiologic typing of coagulase
      negative staphylococci.
AB  - The lack of an adequate typing system hampers our understanding of the
      epidemiology of infections caused by coagulase-negative staphylococci (CoNS).
      CoNS have become recognized as important nosocomial pathogens and the principal
      cause of infections associated with invasive devices. Sensitive, specific, and
      convenient methods are needed to evaluate whether implementing infection control
      guidelines reduces the risk of nosocomial infections from CoNS and other
      pathogens. The Microbial Identification System (MIDI) (Microbial ID Inc., Newark,
      Del.), a semiautomated system for fatty acid methyl ester analysis, shows
      considerable promise for clinical and epidemiologic applications. Its predictive
      accuracy and reliability were tested by using epidemiologically related and
      replicated CoNS isolates as well as CoNS from epidemiologically unrelated
      clinical infections, which were obtained from five established hospital culture
      collections in diverse geographic locations. Two hundred isolates were fully
      characterized in 5 days by one person using MIDI, and the results were similar to
      those produced by more expensive and time-consuming conventional typing methods.
      MIDI appears to be a useful screening tool that could be used before more
      expensive and labor-intensive molecular methods. It offers important advantages
      to hospital epidemiologists and clinical microbiologists who must identify and
      type CoNS isolates.

PMID- 7814535
TI  - Concordance of endotoxemia with gram-negative bacteremia in patients with gram
      negative sepsis: a meta-analysis.
AB  - The Limulus amebocyte lysate (LAL) assay is a sensitive method for detecting
      endotoxin. Using gram-negative (GN) bacteremia as the basis for comparison,
      concordance with endotoxemia in 45 studies could be expressed as an odds ratio.
      Calculation of summary odds ratios by the Mantel-Haenszel-Peto method indicated
      that the concordance of the results was no higher by the chromogenic LAL assay
      than by the gelation version, and the sensitivity was improved by only 11% (62
      versus 51%). Endotoxemia was detected in 77 (68%) of 114 patients with bacteremia
      caused by an organism that was not a member of the family Enterobacteriaceae,
      whereas endotoxemia was detected in only 120 (45%) of 269 patients with
      bacteremia caused by a member of the family Enterobacteriaceae or an anaerobe (P
      < 0.001). This difference was also apparent for patients with GN bacteremia for
      whom a fatal outcome had been recorded. The prevalence of GN bacteremia in the
      tested population and the type of etiological agent are critical and previously
      unrecognized variables which affect the interpretation of the LAL test in
      patients with suspected sepsis.

PMID- 7814536
TI  - Comparison of four enzyme immunoassays for detection of immunoglobulin M
      antibodies against rubella virus.
AB  - We evaluated four tests for the detection of rubella virus-specific
      immunoglobulin M antibodies. Primarily, consecutive serum samples were tested by
      two different assays. Selected panels of sera from patients with proven or likely
      recent rubella and false-positive and true-negative results in the two primary
      assays were further tested with two recently developed, fully automated
      techniques. The four tests were comparable in overall accuracy, but their dynamic
      ranges may differ considerably. Ways to optimize the predictive values are
      discussed. We conclude that automated assays may be used without causing
      significant changes in diagnostic accuracy or distortions in notifications of the
      incidence of rubella compared with the use of established tools.

PMID- 7814537
TI  - Rendering of mycobacteria safe for molecular diagnostic studies and development
      of a lysis method for strand displacement amplification and PCR.
AB  - Two criteria must be met before mycobacterial specimens can be tested by DNA
      amplification methods: (i) the sample must be rendered noninfectious, and (ii)
      the organisms must be lysed to free the DNA. Previous publications reporting DNA
      amplification of mycobacteria have concentrated on lysis and amplification
      procedures and have not addressed the issue of sample safety. We have shown that
      heating of samples below 100 degrees C may not consistently kill mycobacteria;
      however, heating at 100 degrees C in a boiling-water bath or a forced-air oven
      for a minimum of 5 min kills mycobacteria, including Mycobacterium
      thermoresistibile. Furthermore, heating at 100 degrees C for 30 min consistently
      lyses mycobacteria to produce short fragments of DNA that are suitable for
      amplification by PCR and strand displacement amplification. This procedure works
      with clinical samples digested by the n-acetyl cysteine-NaOH method as well as
      with suspensions of organisms in phosphate buffer. This paper also demonstrates
      the feasibility of using strand displacement amplification with clinical
      specimens.

PMID- 7814538
TI  - Detection of Ehrlichia risticii from feces of infected horses by immunomagnetic
      separation and PCR.
AB  - Potomac horse fever, caused by Ehrlichia risticii, is an important disease of
      equines. The major features of the disease are fever, leukopenia, and diarrhea.
      The organism has been detected from the blood mononuclear cells of infected
      horses, but its presence in the feces has not been known. A method for
      immunomagnetic separation of E. risticii from the feces of infected horses was
      developed, and the separated organisms were detected by PCR. Coating
      immunomagnetic beads (Dynabeads) with a 1:5 dilution of rabbit anti-E. risticii
      serum and incubating the Dynabeads with fecal samples for 25 min at room
      temperature gave optimum results. E. risticii was detected from the feces during
      the course of diarrhea from two experimentally infected horses. In horse 1,
      watery diarrhea occurred from days 11 to 16 postinfection (p.i.), after which the
      feces became soft on day 17 p.i. and then returned to normal. The organisms were
      first detected from the feces on day 11 p.i., peaked on day 13 p.i., and then
      gradually decreased until day 16 p.i., after which they became undetectable. In
      horse 2, first, on day 12 p.i., there was soft feces which continued and
      progressed to diarrhea on day 17 p.i. The feces became normal after day 18 p.i.
      The organisms in the feces of this horse were first detected on day 12 p.i. and
      peaked on day 14 p.i., after which they declined until day 16 p.i. and then
      became undetectable. In both horses, the number of organisms in the mononuclear
      cells peaked on days 10 and 11 p.i., respectively, 3 days prior to the respective
      peaks in the feces. E. risticii was not detected from the plasma samples obtained
      from these horses. There was a drastic reduction in PCR amplification of E.
      risticii DNA for fecal samples stored frozen at -20 degrees C in comparison with
      those stored at 4 degrees C. The presence of the organism in the feces only
      during the soft- or diarrheal-feces phase supports the previous hypothesis that
      the diarrhea is caused by the organisms replicating in cells lining the
      intestines. This rapid simple method of detection of the organisms from the feces
      will be helpful in diagnostic and epidemiologic studies of Potomac horse fever.

PMID- 7814539
TI  - Quantification of human immunodeficiency virus type 1-infected mononuclear cells
      in peripheral blood of seropositive subjects by newly developed flow cytometry
      analysis of the product of an in situ PCR assay.
AB  - The presence of human immunodeficiency virus type 1 (HIV-1) proviral DNA in
      peripheral blood mononuclear cells (PBMC) of three groups (group 1, more than 500
      CD4+ T cells per microliter; group 2, between 200 and 499 CD4+ T cells per
      microliter; group 3, fewer than 200 CD4+ T cells per microliter) of HIV-1
      infected patients, in different stages of the disease, was determined by using a
      newly developed flow cytometry analysis of the product of in situ PCR assay and
      compared with other markers of viral replication (HIV-1 p24 antigenemia and viral
      isolation). Results showed varied percentages of HIV-1-infected PBMC, ranging
      from 0.6 to 20%. Patients with more than 500 CD4+ T cells per microliter showed
      the lowest percentage of HIV-1-infected PBMC (2.1 +/- 1.7), compared with
      patients with CD4+ T-cell counts of between 200 and 499 per microliter (6.5% +/-
      4.1%; P < 0.001) and patients with fewer than 200 CD4+ T cells per microliter
      (4.9% +/- 4.7%; P < 0.05). The difference in the percentage of HIV-1-infected
      PBMC between group 2 and group 3 patients may in part reflect the loss of CD4+ T
      lymphocytes in more advanced stages of the disease. However, the results clearly
      indicate a striking coincidence between the fall of the CD4+ T-cell count below
      400/microliter and the sharp increase in PBMC virus loading and p24 antigenemia.
      Since the procedure is relatively easy to perform, it could be used to monitor
      the evolution of HIV-1 infection and may prove a useful adjunct in tailoring
      therapeutic strategies.

PMID- 7814540
TI  - Elimination of false-positive serum reactivity in latex agglutination test for
      cryptococcal antigen in human immunodeficiency virus-infected population.
AB  - We recently tested serum from a human immunodeficiency virus-infected patient for
      the presence of cryptococcal antigen using the Meridian latex agglutination (LA)
      test (Cryptococcal Antigen Latex Agglutination System). Two pronase-treated serum
      specimens from the patient had LA titers of 80 and 160, but the patient had no
      evidence of cryptococcal disease. The serum was negative for rheumatoid factor, a
      well-documented cause of false-positive LA reactions. Seven blood culture
      supernatants from the patient were also LA positive, but were culture negative
      for cryptococcus. When the sera and blood culture supernatants were treated with
      0.01 M 2-beta-mercaptoethanol (2-ME), the agglutinating activity was ablated.
      Similar results were seen when the sera were tested by two other commercial LA
      assays. Serum and cerebrospinal fluid specimens from patients with confirmed
      cryptococcal disease were treated with 2-ME, and the results were compared with
      those obtained after pronase (sera) or heat (cerebrospinal fluid) inactivation.
      The titers were identical (n = 56) or within 1 dilution (n = 3). One hundred
      serum specimens from human immunodeficiency virus-seropositive patients with no
      known history of cryptococcal disease were examined to determine the frequency of
      false-positive reactivity in this patient population. Of this group, three were
      positive following pronase treatment. One remained positive after 2-ME treatment;
      the remaining two were negative. These data indicate that 2-ME can be used to
      eliminate nonspecific reactivity in the LA test without affecting true-positive
      results.

PMID- 7814541
TI  - Genital flora in pregnancy and its association with intrauterine growth
      retardation.
AB  - A study of risk factors for intrauterine growth retardation (IUGR) was conducted
      among a cohort of 13,914 pregnant women enrolled in the multicenter Vaginal
      Infections and Prematurity Study. From 23 through 26 weeks of gestational age,
      cultures of specimens from the vagina and cervix were done for group B
      streptococci, Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas
      vaginalis, Candida albicans, Gardnerella vaginalis, Mycoplasma hominis,
      Ureaplasma urealyticum, and anaerobic gram-negative rods belonging to the genera
      Bacteroides, Porphyromonas, and Prevotella. Newborns who were small for their
      gestational age were delivered by 1,251 women, and infants of the appropriate
      weight for their gestational age were delivered by 10,332 women. When controlling
      for ethnicity and smoking and excluding women treated with antibiotics, the
      Mantel-Haenszel adjusted relative risk of IUGR was 1.16 for Bacteroides,
      Prevotella, and Porphyromonas spp. (95% confidence interval [95% CI], 1.01 to
      1.33), 1.16 for M. hominis (95% CI, 1.04 to 1.29), 1.20 for U. urealyticum (95%
      CI, 1.05 to 1.38), and 1.22 for T. vaginalis (95% CI, 1.05 to 1.42). There was
      also a strong and significant trend for an increasing risk of IUGR with the
      number of these four microbes recovered. Among women colonized with all four
      isolates, the adjusted odds ratio of IUGR was 1.79 (95% CI, 1.27 to 2.52) in
      comparison with women not colonized with any of these microorganisms. Group B
      streptococci, N. gonorrhoeae, C. trachomatis, and C. albicans were not
      significantly associated with IUGR. These results suggest that infection is
      associated with some cases of IUGR and that specific microorganisms, alone or in
      combination, are involved. Since genital isolates are highly correlated with each
      other, the relative contribution of each microbe is difficult to determine.

PMID- 7814542
TI  - Rapid discrimination of Mycobacterium tuberculosis strains by random amplified
      polymorphic DNA analysis.
AB  - Investigations of the epidemiology of tuberculosis have been hampered by the lack
      of strain-specific markers that can be used to differentiate isolates of
      Mycobacterium tuberculosis. We report the development of a rapid protocol for
      random amplified polymorphic DNA analysis which included the use of a
      commercially available DNA extraction kit (GeneReleaser). This was applied to 14
      strains of M. tuberculosis, including strains associated with temporal and
      geographical clusters of tuberculosis in the United Kingdom and those from India,
      Africa, and Saudi Arabia. Strains of M. tuberculosis could be discriminated in
      about 8 h by this method, which is therefore a rapid and simple alternative to
      restriction fragment length polymorphism analysis.

PMID- 7814543
TI  - Rapid detection of vancomycin-resistant enterococci.
AB  - Campylobacter blood agar with clindamycin incubated in 6% CO2 served as a medium
      to both screen for vancomycin resistance and select for presumptive enterococci.
      Colonies that grew on the medium were specifically identified as enterococci
      within 30 min by the pyroglutamyl-beta-naphthylamide and rapid bile esculin
      tests. The combination of a selective medium plus rapid enzyme substrate tests
      offered an inexpensive means to enumerate vancomycin-resistant enterococci from
      specimens by using readily available reagents.

PMID- 7814544
TI  - Characterization of strains of Neisseria meningitidis recovered from complement
      sufficient and complement-deficient patients in the Western Cape Province, South
      Africa.
AB  - Complement deficiency has been associated with increased susceptibility to
      meningococcal disease. In order to determine whether special meningococcal
      strains caused disease in complement-deficient (CD) patients, 17 Neisseria
      meningitidis strains recovered from patients in the Western Cape Province, South
      Africa, known to be CD were compared with 124 routine isolates obtained from
      patients living in the same area. Serogrouping of the strains from the CD
      subjects revealed that the common serogroups, particularly serogroup B,
      predominated. However, the prevalence of rare serogroups among isolates from CD
      subjects was significantly higher than that found among isolates from the control
      group. Sero- and subtyping of the class 1 and class 2 or 3 outer membrane
      proteins showed no significant difference between isolates from CD subjects and
      the routine clinical isolates. Multilocus enzyme electrophoresis of the 141
      isolates revealed six clusters of electrophoretic types (ETs) and two unrelated
      ETs. The same degree of genetic diversity existed in ETs of isolates from CD
      subjects and the control group. However, the ET-5 complex, which is known to be
      associated with epidemic disease, was found in 22 (18%) of the routine clinical
      isolates but in none of the isolates from the CD subjects. This difference was
      marginally significant. What was highly significant was the finding that 8 of the
      17 isolates from CD subjects were in one ET cluster, cluster F, which comprised a
      total of 20 isolates. Thus, our results show a difference in the clonal
      compositions of the strains that infect CD subjects in comparison with the clonal
      compositions of those that cause clinical infections in the population at large.

PMID- 7814545
TI  - Immunoaffinity purification of baculovirus-expressed rubella virus E1 for
      diagnostic purposes.
AB  - Three monoclonal antibodies, termed 4E10, 1E11:10, and 2D9:1, were generated
      against rubella virus. Immunoblot analysis with purified authentic rubella virus
      or recombinant baculovirus-expressed rubella virus structural proteins E1, E2,
      and C demonstrated that they were directed against the E1 envelope glycoprotein
      of the rubella virus particle. By using the yeast Ty virus-like particle system,
      it was possible to map the binding site of 1E11:10 within amino acids 236 to 286
      of the E1 protein and the binding sites of 2D9:1 and 4E10 outside this region.
      Immunoaffinity purification with these monoclonal antibodies made it evident that
      they are useful for obtaining large quantities of pure baculovirus-expressed
      rubella virus envelope protein E1. The diagnostic potential of this
      immunoaffinity-purified recombinant rubella virus E1 protein compared with that
      of authentic rubella virus is demonstrated.

PMID- 7814547
TI  - Comparison of sensititre broth microdilution and agar dilution susceptibility
      testing techniques for meropenem to determine accuracy, reproducibility, and
      predictive values.
AB  - The stability, accuracy, reproducibility, and predictive value of Sensititre MIC
      panels containing meropenem (Merrem) were evaluated by using National Committee
      for Clinical Laboratory Standards (NCCLS)-recommended American Type Culture
      Collection (ATCC) strains and 110 selected strains of rapidly growing and
      fastidious aerobes and anaerobes with various degrees of susceptibility to
      meropenem. The NCCLS-recommended agar dilution method was used as a standard
      reference method. Meropenem-containing Sensititre MIC panels were monitored for
      their stabilities at room temperature and reproducibilities over 24 months by
      using six ATCC strains. Ninety-nine percent of the MICs of both meropenem and
      imipenem obtained for NCCLS-recommended ATCC strains were within the established
      ranges after 2 years. The overall agreement (+/- 1 twofold dilution) between the
      Sensititre and the agar dilution meropenem MICs was greater than 93%. The
      predictive value of meropenem MICs for indicating suspeptibility or resistance
      obtained by the Sensititre method was greater than 90%. No major or very major
      interpretive errors were observed, and only 5% of meropenem MICs were associated
      with minor interpretive errors. Problematic organisms were not observed. The
      Sensititre MIC panels containing meropenem offer a convenient and valid
      alternative to the NCCLS reference method for the susceptibility testing of
      potential pathogens likely to be recovered from mixed infections.

PMID- 7814546
TI  - Detection of porcine reproductive and respiratory syndrome virus and efficient
      differentiation between Canadian and European strains by reverse transcription
      and PCR amplification.
AB  - Two sets of oligonucleotide primers (1008PS-1009PR and 1010PLS-1011PLR) were
      designed according to the sequence of the nucleocapsid protein (N) gene of Quebec
      reference strain IAF-exp91 of porcine reproductive and respiratory syndrome virus
      (PRRSV). The primers were used in reverse transcription and PCR (RT-PCR)
      experiments for detection of viral genomic RNA either from infected porcine
      alveolar macrophages (PAM) or tissues from experimentally infected specific
      pathogen-free pigs. Considering the high degree of variation detected between the
      nucleotide sequences of the N genes of IAF-exp91 and Lelystad virus (LV) strains
      of PRRSV, the primers 1008PS-1009PR were referred to as the specific primers,
      since they were chosen in such a manner that they could amplify only sequences
      from IAF-exp91 RNA and not from LV. On the other hand, the primer pair 1010PLS
      1011PLR was common to both strains of PRRSV. When analyzed by agarose gel
      electrophoresis, the products of RT-PCR from each set of primers were resolved as
      single band of the predicted size, the specificity of amplified products being
      confirmed by Southern blotting with a specific IAF-exp91 N gene probe. No
      amplification was observed when RNA was extracted from uninfected PAM or from
      other porcine viruses. As expected, only the common primer pair was able to
      amplify RNA from the Quebec reference strain and two European strains (LV and
      Weybridge). The resulting bands displayed differences in electrophoretic
      mobilities due to the absence of 37 nucleotides in both European strains, thus
      allowing their differentiation from the IAF-exp91 strain. Most of the tissue
      culture-adapted Quebec isolates were detected with both primer pairs. The
      sensitivity of the enzymatic amplification method for detection of PRRSV from
      lung tissues was a 50% tissue culture infective dose of 5. RT-PCR was found to be
      more sensitive than indirect immunofluorescence assay for detection of PRRSV in
      tissues from experimentally infected pigs and as sensitive as virus isolation in
      PAM, especially when combined with Southern blotting with the digoxigenin-labeled
      N probe and chemiluminescence detection.

PMID- 7814548
TI  - A 1-year evaluation of Syva MicroTrak Chlamydia enzyme immunoassay with selective
      confirmation by direct fluorescent-antibody assay in a high-volume laboratory.
AB  - TThe Syva MicroTrak Chlamydia enzyme immunoassay (EIA; Syva Company, San Jose,
      Calif.) with cytospin and direct fluorescent-antibody assay (DFA) confirmation
      was evaluated on 43,630 urogenital specimens over a 1-year period in the
      Provincial Laboratory in Regina, Saskatchewan, Canada. This was a two-phase study
      intended to define a testing algorithm for Chlamydia trachomatis that would be
      both highly accurate and cost-effective in our high-volume (> 3,000 tests per
      month) laboratory. The prevalence of C. trachomatis infection in our population
      is moderate (8 to 9%). In phase 1, we tested 6,022 male and female urogenital
      specimens by EIA. All specimens with optical densities above the cutoff value and
      those within 30% below the cutoff value were retested by DFA. This was 648
      specimens (10.8% of the total). A total of 100% (211 of 211) of the specimens
      with optical densities equal to or greater than 1.00 absorbance unit (AU) above
      the cutoff value, 98.2% (175 of 178) of the specimens with optical densities of
      between 0.500 and 0.999 AU above the cutoff value, and 83% (167 of 201) of the
      specimens with optical densities within 0.499 AU above the cutoff value were
      confirmed to be positive. A total of 12% (7 of 58) of the specimens with optical
      densities within 30% below the cutoff value were positive by DFA. In phase 2, we
      tested 37,608 specimens (32,495 from females; 5,113 from males) by EIA. Only
      those specimens with optical densities of between 0.499 AU above and 30% below
      the cutoff value required confirmation on the basis of data from phase 1 of the
      study. This was 4.5% of all specimens tested. This decrease in the proportion of
      specimens requiring confirmation provides a significant cost savings to the
      laboratory. The testing algorithm gives us a 1-day turnaround time to the final
      confirmed test results. The MicroTrak EIA performed very well in both phases of
      the study, with a sensitivity, specificity, positive predictive value, and
      negative predictive value of 96.1, 99.1, 90.3, and 99.7%, respectively, in phase
      2. We suggest that for laboratories that use EIA for Chlamydia testing, a study
      such as this one will identify an appropriate optical density range for
      confirmatory testing for samples from that particular population.

PMID- 7814549
TI  - Stabilities of quantitative plasma culture for human immunodeficiency virus, RNA,
      and p24 antigen from samples collected in VACUTAINER CPT and standard VACUTAINER
      tubes.
AB  - We evaluated the stability of human immunodeficiency virus (HIV) load markers
      from blood samples collected in VACUTAINER CPT or standard VACUTAINER brand tubes
      using sodium heparin or sodium citrate as anticoagulants. Quantitative plasma
      culture and p24 antigen concentrations were determined, and HIV RNA levels in
      plasma were measured by both reverse transcription-PCR-enzyme-linked
      immunosorbent assay (RT-PCR-ELISA) and branched DNA methods. All tubes were
      stored at room temperature for analysis at 2, 24, 48, and 72 h after the blood
      samples were drawn. No difference was seen between tube types with respect to the
      HIV titer in plasma or the positivity rate for all samples that demonstrated a
      fall in titer over time. Unbound p24 antigen levels in plasma decreased during
      the initial 48-h period in both tube types. Immune complex-dissociated p24
      antigen levels decreased in CPT tubes but not in standard VACUTAINER tubes. The
      HIV RNA copy number in plasma measured by RT-PCR-ELISA was stable in most
      subjects and was significantly higher in CPT tubes than in standard VACUTAINER
      tubes at 24 and 72 h after the blood samples were drawn. The branched DNA probe
      assay detected a significant decline in HIV RNA equivalent in plasma over 72 h in
      both collection tubes, the decline being more dramatic in the standard VACUTAINER
      tube than the CPT tube. Overall, interday variability suggests that samples
      collected for a particular assay should be processed at the same time after blood
      is drawn and that a particular tube type be used throughout a given study.

PMID- 7814550
TI  - Evaluation of two BBL Crystal systems for identification of some clinically
      important gram-negative bacteria.
AB  - The BBL Crystal system (Becton Dickinson Microbiology Systems, Cockeysville, Md.)
      is a miniaturized bacterial identification method employing modified conventional
      and chromogenic substrates. Two products are currently available, the Rapid
      Stool/Enteric ID Kit and the Enteric/Nonfermenter ID Kit, each comprising thirty
      tests. We report an evaluation of both systems (using database version 1.1 for
      both) in the identification of 51 gram-negative taxa likely to be encountered
      commonly in the clinical laboratory. In all, 266 strains were tested in the
      Enteric/Nonfermenter ID Kit, and these represented 36 taxa of the family
      Enterobacteriaceae (188 strains), 5 oxidase-positive fermentative taxa (26
      strains), and 10 nonfermentative taxa (52 strains). The majority of these same
      strains (203 of 266) were also tested in the Rapid Stool/Enteric ID Kit. The
      Enteric/Nonfermenter ID Kit performed as follows: Enterobacteriaceae, 93%
      correct, 6% not identified, and 1% incorrect; oxidase-positive fermenters, 88,
      12, and 0%, respectively; and nonfermenters, 100% correct, although several only
      to the genus or group level. The Rapid Stool/Enteric ID Kit gave the following
      results: Enterobacteriaceae, 91% correct, 7% not identified, and 2% incorrect;
      oxidase-positive fermenters, 80, 13, and 7%, respectively (but results were based
      on only 15 strains); and nonfermenters, 100% correct (but results were based on
      only 11 strains). We found the systems extremely easy and rapid to use, and for
      the Enteric/Nonfermenter ID Kit an identification rate of 100% in 40 of 51 taxa
      was achieved, with corresponding figures of 29 of 39 taxa for the Rapid
      Stool/Enteric ID Kit.

PMID- 7814552
TI  - Comparison of PCR with culture for detection of Ureaplasma urealyticum in
      clinical samples from patients with urogenital infections.
AB  - PCR was compared with culture for the detection of Ureaplasma urealyticum in 50
      specimens, including sperm, urine, and prostate secretions, from hospital
      patients with urogenital infections. Five positive and a further four doubtful
      diagnoses were made by culture, whereas PCR detected U. urealyticum in 12
      samples. PCR also was faster than culturing. The increased sensitivity and
      shorter time requirement of PCR support its further development for the diagnosis
      of U. urealyticum infection.

PMID- 7814551
TI  - Development of nested PCR assays for detection of bovine respiratory syncytial
      virus in clinical samples.
AB  - Two nested PCR assays were developed for the detection of bovine respiratory
      syncytial virus (BRSV). Primers were selected from the gene encoding the F fusion
      protein (PCR-F) and the gene encoding the G attachment protein (PCR-G).
      Biotinylated oligonucleotide probes, termed F and G, were selected for the
      hybridization of the respective PCR products. The sensitivities of the PCR-F and
      PCR-G assays were similar, both detecting 0.1 tissue culture infective dose of
      the virus. The PCR-F assay amplified all bovine strains and one human strain
      (RS32) tested. No cross-reactions were observed with nine heterologous
      respiratory viruses. PCR-F products of bovine and human RSV strains were
      discriminated by using endonuclease restriction enzyme ScaI, which specifically
      cleaved, products of BRSV. Oligonucleotide probe F was also specific for products
      of BRSV. The PCR-G assay detected all bovine strains and none of the human
      strains tested. A faint electrophoretic band was also observed with products of
      Sendai virus. However, probe G did not hybridize with this product, only with
      products of BRSV. Nasal swabs collected from cattle with no symptoms and cattle
      in the acute stage of respiratory disease were analyzed for BRSV by the
      immunofluorescence (IF) method and by the PCR-F and PCR-G assays. The virus was
      detected by the PCR assays in 31 of 35 (89%) samples tested. Only 23 samples
      (66%) were positive by the IF method, and these samples were also positive by
      both the PCR-F and PCR-G assays. The 31 samples detected as positive by PCR
      originated from cattle presenting clinical signs of acute respiratory disease;
      the four PCR-negative samples originated from clinically asymptomatic neighboring
      cattle. All sampled animals subsequently seroconverted and became reactive to
      BRSV. Thus, the detection of BRSV by PCR correlated with clinical observations
      and was considerably more sensitive (66 versus 89%) than IF. These results
      indicate that both nested PCR assays provide rapid and sensitive means for the
      detection of BRSV infection in cattle. Considering its higher specificity, the
      PCR-F assay can be recommended as the method of choice in the analysis of
      clinical specimens of BRSV.

PMID- 7814553
TI  - Comparison of three commercial MIC systems, E test, fastidious antimicrobial
      susceptibility panel, and FOX fastidious panel, for confirmation of penicillin
      and cephalosporin resistance in Streptococcus pneumoniae.
AB  - The performances of three commercial broth microdilution MIC assays adapted for
      use with fastidious organisms--the E test (ET), Fastidious Antimicrobial
      Susceptibility panel (FAS), and FOX Fastidious panel (FOX)--were compared with a
      MIC using Mueller-Hinton broth with 5% lysed horse blood (MHLHB) to confirm
      penicillin and cephalosporin resistance in clinical isolates of Streptococcus
      pneumoniae. Of the isolates screened for penicillin resistance, 5 (12.8%) were
      categorized as susceptible, 16 (41.0%) were categorized as intermediate, and 18
      (46.2%) were categorized as resistant by MHLHB. Only the isolates exhibiting
      intermediate-to-resistant MICs were included in the comparison. Agreement within
      +/- 1 log2 dilution was found in 91, 21, and 76% of the ET, FAS, and FOX MICs,
      respectively, compared with the MHLHB MIC. No very major or major discrepancies
      occurred with the ET or FOX; however, two very major interpretive errors occurred
      with the FAS. Agreement between the ET and MHLHB for cefotaxime, ceftriaxone, and
      cefuroxime was 88, 85, and 100%, respectively. Less than 50% of cephalosporin
      MICs categorized as > 0.5 microgram/ml by MHLHB were detected by FAS or FOX. Of
      the methods compared, the ET was the most reliable alternative for susceptibility
      testing of pneumococci.

PMID- 7814554
TI  - Diagnosis of cutaneous leishmaniasis and species discrimination of parasites by
      PCR and hybridization.
AB  - The aim of this study was to assess the efficacy of PCR methodology in
      establishing the diagnosis of cutaneous leishmaniasis in patients from areas of
      endemicity in Venezuela. Biopsies from 233 patients with cutaneous ulcers
      suggestive of leishmaniasis were analyzed by PCR, employing oligonucleotides
      directed against conserved regions of kinetoplast DNA (kDNA), and the PCR
      products were then hybridized to nonradioactively labeled, species-specific,
      cloned kDNA fragments. The ability of PCR to detect Leishmania cells was compared
      with those of the conventional methodologies: skin testing with killed
      promastigotes (Montenegro test), examination of Giemsa-stained biopsy smears, and
      in vitro culture of biopsy tissue. The PCR-hybridization technique detected the
      presence of Leishmania cells in 98% of patients clinically diagnosed as having
      leishmaniasis and also positive by the Montenegro skin test. In comparison,
      leishmania positivity was found in only 42% of cultures and 64% of biopsy smears.
      By hybridizing the PCR product to new kDNA probes specific for either Leishmania
      mexicana or Leishmania braziliensis, we found that both species are major causes
      of cutaneous leishmaniasis in Venezuela, and the species identification was
      confirmed by restriction enzyme analysis of kDNA from biopsy cultures. This work
      demonstrates that PCR coupled with hybridization is useful not only for the
      diagnosis of cutaneous leishmaniasis but also for the taxonomic discrimination
      essential for both epidemiology and therapy. This technique can be used to
      diagnose leishmaniasis in a country in which the disease is endemic and can
      perhaps be adapted for use in a rural clinic.

PMID- 7814555
TI  - Strain relatedness of Candida albicans strains isolated from children with
      leukemia and their bedside parents.
AB  - Candida yeasts are occasionally recovered from patients with leukemia in spite of
      antifungal therapy used during chemotherapy. It is not yet known whether yeasts
      in these patients are of endogenous or exogenous origin. We examined the strain
      relatedness of Candida albicans isolated from three patients with leukemia (A, B,
      and C) and their bedside parents using pulsed-field gel electrophoresis (PFGE),
      restriction fragment length polymorphism (RFLP) by SmaI digestion, and the
      Southern hybridization patterns of the RFLPs by the C. albicans-specific probe
      RPS1. SmaI digestion and Southern hybridization by RPS1 showed identical or
      similar patterns among Candida isolates in patients A and his mother, although
      their karyotypes were different. Isolates from patients B and both parents showed
      identical electrophoretic karyotypes, SmaI digestion patterns, and hybridization
      patterns. Since electrophoretic karyotypes are more variable than RFLPs and their
      hybridization patterns, the identity of the last two suggests a close relatedness
      between strains. Our results also suggest that transmission of yeast strains may
      have occurred between patient A and his mother and between patient B and her
      parents. Isolates from patient C and her mother are thought to have originated
      from different strains, since different patterns were obtained in electrophoretic
      karyotypes, SmaI digestion patterns, and Southern hybridization patterns.

PMID- 7814556
TI  - Comparison of plasma PCR and bronchoalveolar lavage fluid culture for detection
      of cytomegalovirus infection in adult bone marrow transplant recipients.
AB  - Plasma PCR for human cytomegalovirus (CMV) DNA was compared with bronchoalveolar
      lavage (BAL) fluid culture as an indicator for disseminated CMV infection.
      Thirteen (32.5%) of 40 consecutive bone marrow transplant (BMT) recipients were
      BAL fluid culture positive for CMV on day 35 post-BMT, and 9 (69%) of the 13 had
      positive plasma PCRs between days 28 and 49. Of the 27 with negative BAL fluid
      cultures, 2 (7%) had positive plasma PCRs (P < 0.001). Plasma CMV DNA in BMT
      recipients is a useful clinical marker for serious infection.

PMID- 7814557
TI  - Opacification of Middlebrook agar as an aid in distinguishing Nocardia farcinica
      within the Nocardia asteroides complex.
AB  - Among 58 aerobic actinomycetes isolated from different sources and geographical
      locations, none of 23 Nocardia asteroides isolates, at 18 N. farcinica isolates,
      1 of 5 N. otitidiscaviarum isolates, and 1 of 4 Rhodococcus species isolates
      opacified Middlebrook 7H10 medium. Within the N. asteroides complex, this
      characteristic, together with growth at 45 degrees C and resistance to each of
      erythromycin, cefotaxime, and tobramycin, provides a simple means of
      distinguishing N. farcinica from N. asteroides.

PMID- 7814558
TI  - Analysis of hepatitis C virus isolates among healthy blood donors and drug
      addicts in Chiang Mai, Thailand.
AB  - Hepatitis C virus (HCV) isolates obtained from 25 anti-HCV antibody-positive
      healthy blood donors and 29 drug addicts in Chiang Mai, Thailand, were analyzed.
      HCV RNA was detected in 23 blood donor samples (92%) and 24 drug addict blood
      samples (83%) by PCR for a portion of the NS5 region. Subtype analysis revealed
      that HCV type 3a (HCV-3a) was the prevailing subtype (30%), which was followed in
      prevalence by HCV-1a (21%), -1b (13%), -3b (13%), and -6a (2%). Six (13%) of the
      47 isolates showed low sequence similarities with known types and subtypes. The
      sequence variants could be grouped into four branches in a molecular evolutionary
      phylogenetic tree.

PMID- 7814559
TI  - Distribution of viral genotypes in Italy determined by hepatitis C virus typing
      by DNA immunoassay.
AB  - The distribution of hepatitis C virus (HCV) genotypes in Italy was investigated
      by PCR amplification of the E1 region and hybridization with type I- and type II
      specific nonisotopic probes. Positive PCR results were obtained for 65 of 72
      patients (90.3%). Type I was detected in 13 of 72 patients (18%), type II was
      detected in 39 patients (54.2%), and a mixed type I-type II infection was
      detected in 7 patients (9.7%). Six amplification products not classified by this
      method shared a low level of homology with HCV types I and II. HCV type I was
      significantly associated with human immunodeficiency virus, whereas HCV type II
      was detected in older subjects who were negative for human immunodeficiency virus
      markers. These results indicate different epidemiological distributions of HCV
      types I and II in Italy.

PMID- 7814560
TI  - Case report and review of septicemia due to Serratia ficaria.
AB  - Serratia ficaria was first described in 1979 as part of the fig tree ecosystem
      (P.A.D. Grimont, F. Grimont, and M. P. Starr, Curr. Microbiol. 2:277-282, 1979).
      Since then, it has been isolated from clinical specimens from a few human
      patients (C. Bollet, J. Freney, P. de Micco, F. Grimont, and P.A.D. Grimont, Med.
      Mal. Infect. 20:97-100, 1990; J.A. Brouillard, W. Hansen, and A. Compere, J.
      Clin. Microbiol. 19:902-904, 1984; H. Darbas, H. Jean-Pierre, G. Boyer, and M.
      Riviere, Med. Mal. Infect. 23:269-270, 1993; V.J. Gill, J.J. Farmer, III, P.A.D.
      Grimont, M.A. Asbury, and C.L. McIntosh, J. Clin. Microbiol. 14:234-236, 1981;
      F.D. Pien and J.J. Farmer III, South. Med. J. 76:1591-1592, 1983; C. Richard, J.
      de Coquet, and C. Suc, Med. Mal. Infect. 19:45-47, 1989), but the pathogenicity
      of S. ficaria was always questionable. We are reporting the case of an aged
      cancer patient who developed S. ficaria septicemia. The habitat of this organism
      and its potential role as a pathogen are discussed.

PMID- 7814561
TI  - Standardized microtiter assay for determination of syncytium-inducing phenotypes
      of clinical human immunodeficiency virus type 1 isolates.
AB  - A standardized assay in 96-well microtiter plates for syncytium-inducing (SI)
      human immunodeficiency virus type 1 phenotype detection using MT-2 cells has been
      developed. SI variants were found in 67% of the patients with advanced human
      immunodeficiency virus disease. The occurrence of the SI phenotype increased with
      lower CD4+ counts. There was no association between p24 antigenemia and the SI
      phenotype.

PMID- 7814562
TI  - Detection of human parvovirus B19 DNA PCR products by RNA probe hybridization
      enzyme immunoassay.
AB  - We have developed an RNA probe hybridization enzyme immunoassay for detection of
      human parvovirus B19 PCR-amplified DNA. The assay is easy to perform and
      increases assay sensitivity without the added inconvenience and risk of false
      positive results associated with nested PCR.

PMID- 7814563
TI  - High frequency of yeast carriage on hands of hospital personnel.
AB  - The hands of 36 nurses and 21 nonnursing hospital employees were tested by
      culture with a modification of the broth wash technique. Seventy-five percent of
      the nurses and 81% of the nonnurses were found to harbor yeasts on their hands;
      58% of nurses and 38% of nonnurses were carrying Candida spp.

PMID- 7814564
TI  - First report of involvement of Nodulisporium species in human disease.
AB  - Allergic fungal sinusitis is a common disease that results from a
      hypersensitivity reaction mounted by the host against fungi living in the
      paranasal sinuses. We have recently treated a patient with allergic fungal
      sinusitis due to a Nodulisporium species. This is the first description of a
      Nodulisporium species involved in human disease. The genus Nodulisporium contains
      both dematiaceous and nondematiaceous members. These fungi occur worldwide in
      nature, often as accompanying conidial anamorphs of certain wood decay
      ascomycetes. Clinical mycology laboratories may encounter this new agent of
      phaeohyphomycosis.

PMID- 7814565
TI  - Effect of potential interference factors on performance of enzyme immunoassay and
      latex agglutination assay for cryptococcal antigen.
AB  - The PREMIER Cryptococcal Antigen Enzyme Immunoassay (Meridian Diagnostics) did
      not give discrepant results with rheumatoid factor, syneresis fluid, or serum
      macroglobulins from systemic lupus erythematosis patients. The Cryptococcal
      Antigen Latex Agglutination System (Meridian Diagnostics) did cross-react with
      syneresis fluid but not with the other serum factors tested.

PMID- 7814566
TI  - Evaluation of new monoclonal antibody-based latex agglutination test for
      detection of cryptococcal polysaccharide antigen in serum and cerebrospinal
      fluid.
AB  - We evaluated the performance of CRYPTO-LEX (Trinity Laboratories, Inc., Raleigh,
      N. C.), a new mouse immunoglobulin M monoclonal antibody latex agglutination
      reagent which reacts with the capsular polysaccharide of the four serogroups of
      Cryptococcus neoformans. This test was compared with CALAS (Meridian Diagnostics,
      Cincinnati, Ohio) for the ability to detect cryptococcal antigen in serum and
      cerebrospinal fluid (CSF). A total of 580 clinical specimens (327 serum and 253
      CSF samples), primarily from human immunodeficiency virus-infected patients, were
      tested in this study. Sixty-seven specimens (44 serum and 23 CSF samples) were
      positive for cryptococcal antigen with both tests, and 511 (282 serum and 229 CSF
      samples) were negative. The two latex reagents agreed for 326 of 327 serum
      specimens (44 positives and 282 negatives). One serum specimen with a titer of
      1:2 was CALAS positive but CRYPTO-LEX negative. The titer correlation coefficient
      for the two tests was 0.884 when two highly discordant serum specimens were
      eliminated from analysis of the data. The two latex tests agreed for 252 of 253
      CSF specimens (23 positives and 229 negatives). One specimen with a titer of 1:2
      was positive with CALAS and negative by CRYPTO-LEX. The correlation coefficient
      of the two tests for CSF titers was 0.886. The sensitivity and specificity of
      CRYPTO-LEX were 97 and 100%, respectively, with a 99.6% correlation with CALAS.
      These data show that the performance of CRYPTO-LEX is comparable to that of CALAS
      for detection of cryptococcal antigen in serum and CSF.

PMID- 7814567
TI  - Demonstration of Borrelia burgdorferi DNA in urine samples from healthy humans
      whose sera contain B. burgdorferi-specific antibodies.
AB  - Since the possibility of asymptomatic infection with Borrelia burgdorferi has
      been suggested by a positive serology found in healthy subjects, we hypothesized
      that these subjects might excrete borrelial DNA sequences in urine as happens in
      patients with Lyme borreliosis. We found borrelial sequences by nested PCR in the
      urine samples from 3 of 13 healthy B. burgdorferi antibody-positive adults but
      not in urine samples from 79 antibody-negative healthy controls. After therapy
      with doxycycline, the urine samples were repeatedly negative for B. burgdorferi
      DNA. We conclude that urinary excretion of borrelial DNA sequences may occur in
      seropositive healthy subjects during asymptomatic infection. Demonstration of
      such sequences in urine must be interpreted cautiously and may not necessarily
      prove a borrelial cause of disease.

PMID- 7814568
TI  - Rotavirus serotypes causing severe acute diarrhea in young children in six
      Australian cities, 1989 to 1992.
AB  - Rotavirus VP7 serotypes were identified in stools from 72.9% (1,302/1,784) of
      hospitalized Australian children in six cities (1989 to 1992) and comprised 1,088
      (83.6%) serotype G1 isolates, 84 (6.4%) serotype G2 isolates, 64 (4.9%) serotype
      G3 isolates, 49 (3.8%) serotype G4 isolates, and 17 (1.3%) isolates of mixed
      serotypes. The most densely populated cities yielded the greatest diversity of
      serotypes.

PMID- 7814569
TI  - Evaluation of E test as a rapid method for determining MICs for nutritionally
      variant streptococci.
AB  - E test was evaluated as an alternative rapid and simple method of MIC estimation
      for nutritionally variant streptococci. E test with various media was compared
      with conventional broth and plate dilution techniques supplemented with 0.001%
      (wt/vol) pyridoxal hydrochloride (vitamin B6). Of the 14 strains tested with E
      test, isosensitest agar supplemented with 5% defibrinated horse blood and 0.001%
      pyridoxal HCl, with and without 0.01% cysteine, gave complete agreement within
      one twofold-dilution titer of the agar reference method and between 93 and 86%
      agreement within one twofold-dilution titer of the broth reference method. E test
      MICs with other media were comparable; however, these were considerably more
      difficult to interpret. Use of Mueller-Hinton and Columbia-based supplemented
      agar showed hazy growth and double zoning around the endpoint, respectively. The
      addition of 0.01% (wt/vol) cysteine to media exhibited no significant effect, and
      incubation in 5% carbon dioxide (CO2) did not affect MICs.

PMID- 7814570
TI  - Genome analysis of South American adenovirus strains of serotype 7 collected over
      a 7-year period.
AB  - DNA restriction analysis was carried out on a sample of 212 epidemiologically
      unrelated adenovirus (Ad) strains of serotype 7 isolated in Chile, Uruguay, and
      Argentina from nasopharyngeal aspirates of children with acute lower respiratory
      disease between 1984 and 1990. The identified genome types were Ad7b (n = 12),
      Ad7c (n = 21), and Ad7h (n = 179). The analysis of the occurrence of the three
      genome types throughout the study period revealed that Ad7c was the predominant
      virulent variant in 1984 and indicated that a shift to genome type 7h took place
      in 1986. Ad7b cocirculated with the other genomic variants at a relatively low
      frequence.

PMID- 7814571
TI  - Usefulness of PCR for detection of Pneumocystis carinii DNA.
AB  - Diagnosis of Pneumocystis carinii pneumonia is based on the identification of the
      various stages of the parasite in lung samples by standard staining techniques.
      We therefore assessed the value of the PCR for detection of P. carinii in
      bronchoalveolar lavage, induced sputum, and blood samples relative to that of
      standard staining techniques.

PMID- 7814572
TI  - Demonstration of persistence of Salmonella typhimurium in an AIDS patient by
      molecular methods.
AB  - We document microbiological persistence of the same Salmonella typhimurium strain
      in an AIDS patient during 7 months of clinical observation despite prolonged
      quinolone therapy. Persistence was demonstrated by phage types that closely
      resembled one another, similar antibiotic resistance patterns, conserved
      restriction fragment length polymorphism of chromosomal DNA digested with
      different DNA restriction enzymes, identical ribotypes, and IS200 types in four
      characterized sequential isolates of S. typhimurium.

PMID- 7814573
TI  - Hafnia alvei in stool specimens from patients with diarrhea and healthy controls.
AB  - We found an epidemiological association of Hafnia alvei with diarrhea, because
      the organism was isolated from 12 of 77 (16%) adult Finnish tourists to Morocco
      who developed diarrhea and from 0 of 321 tourists without diarrhea (P < 0.001).
      From another group of 112 adult Finnish diarrheal patients, only 2 (2%) yielded
      H. alvei. In contrast to some Bangladeshi strains of H. alvei, the Finnish
      strains were negative for the attachment-effacement lesion by an in vitro
      fluorescent acting staining test and also did not show homology to the
      Escherichia coli attachment-effacement gene (eaeA) by PCR. These results suggest
      that a mechanism or mechanisms other than the attachment-effacement lesion may
      also be involved in the association of H. alvei with diarrhea.

PMID- 7814574
TI  - Additional data on clinical isolates of Campylobacter mucosalis.

PMID- 7814575
TI  - Pitfalls in immunoblot detection of Aspergillus antigens associated with invasive
      infection.

PMID- 7814576
TI  - Utility of quantitative enzyme immunoassay reactivity for predicting human
      immunodeficiency virus seropositivity in low- and high-prevalence populations.

PMID- 7814577
TI  - E test as susceptibility test for evaluation of Neisseria meningitidis isolates.

PMID- 7814578
TI  - The role of gait analysis in the treatment of cerebral palsy.

PMID- 7814579
TI  - Gait laboratory analysis for preoperative decision making in spastic cerebral
      palsy: is it all it's cracked up to be?

PMID- 7814580
TI  - Is the objective assessment of cerebral palsy gait reproducible?
AB  - It is important to determine the reproducibility of objective measures of gait in
      children with motor disorders in order that the effect of interventions to
      improve gait can be monitored. Data for walking velocity and vertical ground
      reaction force expressed as a percentage of body weight were collected from 15
      normal children and 11 with spastic cerebral palsy. Five recordings were obtained
      for each foot of each child on 3 consecutive days, and calculations of
      variability made for each set of five recordings. Children with cerebral palsy
      had slower walking velocities and greater ground reaction force values, and both
      these parameters had low intraindividual variation for both normal children and
      those with cerebral palsy (coefficients of variation < 12.5%). This good
      reproducibility applied to intrasubject and intraday variability; no learning
      effect was seen over 3 days' recordings. There was no significant difference in
      variability whether the first three recordings or all five were used. These
      techniques of gait measurement in children have good reproducibility and a
      potential role in the objective assessment of medical and surgical interventions.

PMID- 7814581
TI  - Hip function and gait in patients treated for bladder exstrophy.
AB  - Patients with bladder exstrophy demonstrate pubic diastasis with external
      rotation of the ilia and posterolateral orientation of the acetabula. Iliac
      osteotomy is performed to approximate the pubis and thus facilitate the
      genitourinary repair. The role of iliac osteotomy in the correction of gait
      abnormalities is controversial. Our goals in this study were to define the
      presence of hip pathology and gait abnormalities in patients treated for bladder
      exstrophy and to evaluate the effect of iliac osteotomy. We reviewed pelvic
      radiographs and gait studies in 15 children. The treatment included bilateral
      iliac osteotomy in nine of 15 of these patients. We found minor hip dysplasia in
      two patients, but we saw no evidence of subluxation or dislocation. Pubic
      diastasis increased with age and was not related to osteotomy. Patients had
      slightly less passive hip internal rotation than age-matched controls. There was
      no correlation between the restriction of hip internal rotation and the amount of
      pubic diastasis. Two thirds (10 of 15) of the patients exhibited increased lower
      extremity external rotation during gait. None of the subjects demonstrated a
      waddling gait (gluteus medius lurch) described in the literature. Based on our
      results, iliac osteotomy does not affect gait patterns in children with bladder
      exstrophy. However, we believe that it is indicated to improve the results of
      genitourinary repair.

PMID- 7814582
TI  - Walking ability in spina bifida patients: a model for predicting future
      ambulatory status based on sitting balance and motor level.
AB  - Two-hundred six patients with spina bifida were followed from birth to an average
      age of 115 months. We characterized the population in terms of factors which we
      expected to affect walking ability. Two independent predictors of community
      ambulation were identified through regression analysis: sitting balance and motor
      level. We used these variables to develop a mathematical method to predict which
      groups were likely to be independent walkers into adolescence. When we tested
      this equation against our actual population, we correctly characterized walkers
      as such in 92% of the cases. Furthermore, when we applied this equation to
      another random population taken from our clinic, we successfully characterized
      walkers in 92% of the cases. The strength of these observations allows us to
      provide guidelines to parents about the likelihood of their children being able
      to walk independently as adolescents on the basis of motor level and sitting
      balance, which can be assessed at an early age.

PMID- 7814583
TI  - Femoral anteversion and neck-shaft angles in hip instability in cerebral palsy.
AB  - A consecutive sample of 411 hip roentgenograms in 215 patients with cerebral
      palsy was evaluated. Femoral anteversion and neck-shaft angles were measured and
      compared with hip stability indexes to determine which of the two angles is more
      important in hip instability. The correlation coefficients were higher and
      statistically significant for femoral anteversion and lower and statistically
      nonsignificant for neck-shaft angles. These findings suggest that increased
      femoral anteversion has greater correlation than increased coxa valga with hip
      instability in cerebral palsy patients and therefore should be addressed
      primarily when surgically treating these hips.

PMID- 7814584
TI  - Pelvic osteotomies for subluxation of the hip in cerebral palsy.
AB  - Twenty-three pelvic osteotomies (10 Salter, seven Chiari, six Steel) were
      performed on 21 patients with cerebral palsy for hip subluxation or dislocation
      from 1977 to 1986. The principal indication for osteotomy was inadequate coverage
      of the femoral head. Stability was maintained in 19 of 23 hips with an average
      follow-up of 6.14 years (2.0-13.3). The hips showed a significantly improved
      center-edge angle, acetabular angle, Reimers index, and neck-shaft angle. There
      were six failures; painful degenerative joint disease developed in two patients
      and resubluxation or dislocation in four. Pelvic osteotomies can provide hip
      stability in selected cerebral palsy patients.

PMID- 7814585
TI  - A reassessment of spinal stabilization in severe cerebral palsy.
AB  - A homogenous population of 37 institutionalized patients with scoliosis and
      severe cerebral palsy was evaluated to assess the impact of spinal stabilization
      on comfort, function, health, and ease of nursing care. Through a prospective
      care-burden study, a 34-month retrospective analysis, and a healthcare worker
      questionnaire, 17 fused patients with a mean current scoliosis of 35 degrees were
      compared with 20 nonfused patients with a mean scoliosis of 76 degrees. No
      clinically significant differences were noted in pain or pulmonary medication
      utilization or therapy, decubiti, function, or time for daily care. Nevertheless,
      the majority of healthcare workers believed that the fused patients were more
      comfortable.

PMID- 7814588
TI  - Isolated tubercular tenosynovitis in children: report of seven cases.
AB  - Isolated tubercular tenosynovitis is a rare entity, and is extremely rare in
      children. Seven cases of isolated tubercular tenosynovitis are presented, all in
      children in their second decade of life. There were no primary detectable lesions
      elsewhere in the body. Diagnosis in all the cases was obtained by fine-needle
      aspiration cytology. All patients were treated by antitubercular drugs for 18
      months and achieved complete healing and full function. Use of fine-needle
      aspiration cytology in tubercular tenosynovitis is discussed.

PMID- 7814586
TI  - Single-incision combination biopsy (muscle and nerve) in the diagnosis of
      neuromuscular disease in children.
AB  - The diagnosis of specific neuromuscular diseases in infants and children is often
      suspected clinically and confirmed histologically by muscle biopsy. In relatively
      few cases, the differential diagnosis includes hereditary or acquired peripheral
      neuropathies, and nerve biopsy is required for diagnosis. Historically, children
      who needed both muscle and nerve biopsies have had two separate incisions at the
      thigh (muscle) and ankle (nerve) to obtain the specimens. A procedure has been
      developed that employs a single incision on the posterior aspect of the calf,
      which allows for simultaneous muscle (soleus or peroneals) and nerve (sural)
      biopsies. A retrospective study of 22 patients who underwent single-incision
      combination biopsy was performed. Age at time of biopsy ranged from 2 months to
      14 years. Adequate specimens for histologic analysis were obtained in all but one
      case. Histologic diagnoses were made in 32% of the muscle biopsies and 29% of the
      nerve biopsies. Mean follow-up after biopsy was 3 years 6 months. Potentially
      significant complications of nerve biopsy were not seen in this cohort. Single
      incision combination biopsy is the preferred technique when simultaneous muscle
      and nerve biopsies are required. Knowledge of the location of the sural nerve in
      the calf is essential. This technique is relatively less invasive than separate
      muscle and nerve biopsies, allows for the harvest of adequate muscle and nerve
      specimens, is minimally morbid, and can be performed on very young infants.

PMID- 7814587
TI  - Sequelae from septic arthritis of the knee during the first two years of life.
AB  - Fifty septic knees in patients younger than 2 years old at diagnosis were
      examined. Follow-up ranged from 1.1 to 21.3 years (average, 6.2). Twenty-four
      knees were deformed in varus or valgus of 5-40 degrees. Deformity was present
      within 10 months of infection and thereafter was stable. It was due to
      displacement of the epiphysis into a metaphyseal defect, loss of epiphyseal
      cartilage, or both. Growth did not compensate for deformity. Ossific nuclei
      partly or completely disappeared after infection. They were slow to reappear, and
      until maturity, their size and shape did not represent the cartilaginous
      epiphysis. Arthrograms were necessary to evaluate accurately the epiphyseal shape
      and volume.

PMID- 7814589
TI  - Pseudomonas osteochondritis complicating puncture wounds in children.
AB  - Pseudomonas osteochondritis is an uncommon complication of puncture wounds. It
      can have a particularly devastating affect in the growing child, often resulting
      in significant permanent sequelae. To assess the current approach to diagnosis
      and treatment of this condition in children, 15 such cases seen at the Children's
      Hospital of Eastern Ontario between 1975 and 1991 were studied retrospectively.
      Case presentations were similar, with delayed onset of localized pain, swelling,
      and elevated erythrocyte sedimentation rate following a puncture wound. All
      patients had previously received oral antibiotics. Initial radiographic changes
      were rare. All patients were treated with i.v. antibiotics: although most
      required surgical debridement. Complications including recurrence, chronic pain,
      and deformities required sequestrectomies, angular osteotomies, and leg
      lengthening procedures. A high index of suspicion, coupled with aggressive
      medical and surgical treatment, is required for a satisfactory outcome.

PMID- 7814590
TI  - Heel seats and shoe wear.
AB  - Seventy-two children with excessive heel valgus and markedly uneven shoe wear
      were treated by Helfet heel seats for 18-36 months. Of the 52 children reviewed
      in this study, 44 had improved shoe wear. Simple heel seats offer economical
      treatment for children whose foot deformities destroy their shoes.

PMID- 7814591
TI  - Tibial osteotomy as a salvage procedure in the treatment of congenital talipes
      equinovarus.
AB  - Fourteen children (19 feet) ranging in age from 2.1 to 17.0 years (mean, 7.6
      years) underwent tibial osteotomy for treatment of congenital talipes equinovarus
      (CTEV). The indications for tibial osteotomy were persistent or recurrent
      equinovarus deformity and internal rotation of the foot (medial malalignment
      syndrome), in most cases with severe distortion of the hindfoot joints resulting
      from previous operations. In 12 feet (9 children), bi- or triplanar
      supramalleolar osteotomy for the correction of all the elements of the deformity
      was performed. In the remaining cases, external rotation tibial osteotomy below
      the tuberosity in five feet (three children) and supramalleolar in two feet (two
      children) was performed. The follow-up ranged from 1 to 16 years (mean, 4.3
      years). Partial or full improvement, concerning one or more elements of the
      equinovarus deformity, has been achieved in 11 feet (nine children). In eight
      feet (five children), tibial osteotomy did not improve the deformity. There are
      exceptionally rare indications for use of tibial osteotomy in the treatment of
      CTEV or medial malalignment syndrome after failed clubfoot surgery. They concern
      older children and adolescents with secondary osteoarthritis of the feet
      resulting from previous multiple operations.

PMID- 7814592
TI  - Foot deformities in arthrogryposis multiplex congenita.
AB  - Foot deformities are common in arthrogryposis multiplex congenita. In this group
      of 52 patients with this diagnosis, 43 had foot deformities. The involvement was
      bilateral in all cases, and the most common type of deformity was talipes
      equinovarus (72 feet). The primary treatment in 52 of these patients was
      operative. Brockmann's procedure was the preferred method during the earlier
      years and posteromedial or posteromedioplantar release since 1974. Recurrences of
      the deformity are common; 36 operative procedures were done in 15 feet for
      recurrence of talipes equinovarus. The primary operative treatment should be
      extensive enough to correct all components of the deformity. Knee and hip
      deformity will often influence the outcome. Knee deformities especially cause
      problems in retaining the desired position of the feet. Talectomy and bone
      decancellations both seem to be effective in treating recurrences.

PMID- 7814593
TI  - Latent onset unilateral toe-walking secondary to hemangioma of the gastrocnemius.
AB  - Acquired unilateral pes planus due to hemangioma of the gastrocnemius is an
      unusual and rarely reported event. In recent years, three children with latent
      onset unilateral toe-walking due to hemangioma of the proximal gastrocnemius have
      received treatment at our facility. This report details the usual clinical
      syndrome and presents postsurgical results. Our experience suggests that in
      children, a presumptive diagnosis of benign hemangioma of gastrocnemius can be
      predicated on the basis of history, clinical examination, imaging studies, and
      laboratory assessment. In contrast to previous reports recommending primary tumor
      resection, isolated open tendoachilles lengthening can provide acceptable results
      with minimum morbidity.

PMID- 7814594
TI  - Giant-cell tumor of bone: a rare entity in the hands of children.
AB  - Giant-cell tumor of bone is a relatively uncommon tumor in skeletally immature
      patients. It also occurs only infrequently in the hand. We present two cases of
      this tumor occurring in the hands of pediatric patients and discuss the
      literature regarding this disease process, including clinical presentation,
      pathology, and options for treatment.

PMID- 7814595
TI  - Primary bone tumor resectability: the value of serial MRI studies in the
      determination of the feasibility, timing, and extent of tumor resection.
AB  - We report the prospective analysis of 119 magnetic resonance imaging (MRI)
      studies in 41 patients with primary bone tumors performed from January 1984 to
      December 1990 to evaluate the contribution of serial MRI studies in the
      determination of feasibility, timing, and extent of tumor resection. Long
      repetition time (TR)-long echo time (TE) T2-weighted (T2, second echo) imaging
      was the most useful in assessing soft-tissue involvement, and short TR-short TE
      T1-weighted (T1) imaging for documenting the bone marrow changes. The
      feasibility, timing, and extent of resection was determined with the help of MRI
      in 20 cases with only two local recurrences. One study falsely suggested active
      tumor. In four other cases, a treatment decision was made based on the MRI. The
      MRI added significantly to the evaluation by computed tomography, radiographs,
      and bone scans.

PMID- 7814596
TI  - Osteoid osteoma or osteoblastoma of the cervical spine in relation to the
      vertebral artery.
AB  - Osteoid osteoma or osteoblastoma of the cervical spine require complex
      therapeutic solutions in cases in which there is proximity to the vertebral
      artery. We describe four such cases. Generally, resection was efficacious and
      without recurrence, but twice the vertebral artery had to be sacrificed. Although
      we did not find any serious neurological complication, we concluded that a simple
      sacrifice of one of the vertebral arteries is not acceptable, principally because
      of the importance and variability of the unknown radiculomedullary branches of
      the vertebral artery. We discuss the therapeutic strategies for treating these
      lesions, namely preoperative investigations, surgical approaches, and vascular
      control.

PMID- 7814597
TI  - Acquired vitamin D-resistant rickets caused by aggressive osteoblastoma in the
      pelvis: a case report with ten years' follow-up and review of the literature.
AB  - Rickets or osteomalacia secondary to tumor in either bone or soft tissue is rare
      and interesting in that it can be cured after removal of the tumor. The majority
      of the reported cases occurred in adults older than 30 years, and the most
      commonly associated types were vascular and fibrous tumors. We present a new case
      of aggressive osteoblastoma in the ilium, which induced vitamin D-resistant
      rickets in an 8-year, 9-month-old boy. Radiographs and blood chemistry findings
      on admission showed typical features of active hypophosphatemic ricketts. He
      underwent three local excisions of the tumor. At 10-year follow-up, the patient
      was symptom free but short. When a child has symptoms of rickets that develop
      relatively later than ordinary vitamin D-resistant rickets, every effort should
      be made to search out a tumorous lesion before attributing it to a renal origin.

PMID- 7814598
TI  - Postoperative fever in pediatric orthopaedic patients.
AB  - Fever in hospitalized patients causes a great deal of concern. Its value in
      predicting complications, however, is questionable. For this reason, a
      retrospective analysis was performed on 200 records of children's orthopaedic
      admissions. Demographic data, would status, fever work-up, and daily peak
      temperatures were recorded. There were 174 patients who underwent surgical
      procedures and 26 patients who did not have surgery. Seventy-three percent
      (127/174) of the surgical patients had postoperative fever [temperature > 38
      degrees C (100.4 degrees F)] Twenty-seven percent of the nonsurgical patients had
      fever. There were only three acute complications--one pneumonia and two wound
      infections. Complications were easily diagnosed by clinical means. In
      postoperative patients, the accuracy in predicting complications was 28%.
      Postoperative fever is a poor predictor of complications, and, therefore, should
      not delay discharge or indicate investigation for sepsis.

PMID- 7814599
TI  - Infantile torticollis: a review of 624 cases.
AB  - We reviewed 624 cases of infantile torticollis in one centre over a period of 7
      years. The incidence of torticollis was found to be 1.3% in Chinese children. Boy
      to-girl ratio was 3:2. Obstetric histories of the mothers showed a total of 62.2%
      with difficult labour, breech deliveries, or caesarean section, and 6.04% had
      associated congenital anomalies. Of all the cases, 27.88% were found to be
      postural, 35.4% had torticollis that presented with sternomastoid tumor, and
      36.7% presented with muscular torticollis alone. When limitation of neck range
      was considered, 36.7% had a passive rotation deficit > 15 degrees. In patients
      presenting in the early stages, 97% of all infantile torticollis cases resolved
      with conservative treatment, active stimulation, and a passive stretching
      program. For those responding to treatment, the mean treatment period was < 6
      months for varying degrees of neck rotational deficit. Patients with cord-like
      muscular torticollis and a rotational > 30 degrees were more likely to need
      surgery. Presence of sternomastoid tumor alone was not found to increase the
      likelihood of surgery. Musculoskeletal sequelae after torticollis had resolved
      included intermittent head tilt and persistence of mild craniofacial asymmetry.
      We recommend continuous follow-up in cases of infantile torticollis, particularly
      in patients with progression of sternomastoid tumor to muscular torticollis.

PMID- 7814600
TI  - Prostaglandin-induced neonatal periostitis.
AB  - Prostaglandins are being commonly used to maintain the patency of the ductus
      arteriosus in infants with congenital ductal-dependent heart disease. A
      significant and unusual side effect of this drug treatment is the symmetrical
      development of periostitis of the long bones. A review of neonates with
      congenital heart disease requiring prostaglandin treatment at the Children's
      Hospital of Eastern Ontario revealed five infants who developed periostitis, the
      earliest onset being after 14 days of prostaglandin infusion. The drug dosage
      varied in these infants from 0.02 to 0.10 micrograms/kg/min. The periostitis was
      associated with limb pain and considerable swelling of the extremities in all
      children. The periostitis improved on cessation of the prostaglandin infusion,
      and by 6 weeks after the cessation of the drug, the periostitis had decreased
      significantly. Periostitis seemed more dependent on the duration of
      administration of the prostaglandin than on the dosage of prostaglandin
      administered. Awareness of this entity is essential not only for the treatment
      team caring for these infants but also for consultant pediatric orthopaedists to
      avoid excessive investigation for infection, metabolic disease, or vitamin
      deficiencies that resemble prostaglandin-induced periostitis.

PMID- 7814601
TI  - Camptodactyly: classification and results of nonoperative treatment.
AB  - To assess the relationship between clinical presentation and response to
      treatment, we reviewed the management of 59 involved proximal interphalangeal
      (PIP) joints in 22 patients with camptodactyly at a mean follow-up of 33 months.
      This population represented 24 cases of isolated infantile camptodactyly (type
      I), five cases of adolescent camptodactyly (type II), and 30 cases of syndromic
      camptodactyly (type III). Treatment response was assessed through passive range
      of motion measurements. Splinting and close adherence to an occupational therapy
      program were particularly effective for type I digits. We also recommend this
      approach for type II and type III camptodactyly, although severe deformities and
      well-established contractures are more common in these patients. We reserve
      operative intervention for only those patients who fail nonoperative management.

PMID- 7814602
TI  - Leg length discrepancy associated with vivid cutis marmorata.

PMID- 7814603
TI  - Glucagon-like peptide-1 (GLP-1): a piece of the incretin puzzle.

PMID- 7814604
TI  - Localization and functional characterization of rat kidney-specific chloride
      channel, ClC-K1.
AB  - To investigate the physiological role of a kidney-specific chloride channel (ClC
      K1), we sought to determine its exact localization by immunohistochemistry and
      its functional regulation using Xenopus oocyte expression system. The antiserum
      specifically recognized a 70-kD protein in SDS-PAGE of membrane protein from rat
      inner medulla and an in vitro translated ClC-K1 protein. Immunohistochemistry
      revealed that ClC-K1 was exclusively localized to the thin limb of Henle's loop
      in rat inner medulla. In comparison with the immunostaining with anti-aquaporin
      CHIP antibody that only stains the descending thin limb of Henle's loop (tDL),
      ClC-K1 was found to be localized only in the ascending limb (tAL) which has the
      highest chloride permeability among nephron segments. Immunoelectron microscopy
      confirmed that the staining of ClC-K1 in tAL was observed in the region of both
      apical and basolateral plasma membranes. Expressed chloride current in Xenopus
      oocytes by ClC-K1 cRNA was regulated by extracellular pH and extracellular
      calcium. Furosemide inhibited the expressed current (Ki = 100 microM), whereas N
      ethyl-maleimide stimulated the current. These functional characteristics were
      consistent with the in vitro perfusion studies of chloride transport in tAL. The
      localization and the functional characteristics described here indicate that ClC
      K1 is responsible for the transepithelial chloride transport in tAL.

PMID- 7814605
TI  - Regulation of smooth muscle cell scavenger receptor expression in vivo by
      atherogenic diets and in vitro by cytokines.
AB  - Scavenger receptor (ScR)-mediated uptake of modified lipoproteins may contribute
      to the transformation of smooth muscle cells into lipid-laden foam cells during
      atherogenesis. This study examined the in vivo expression of ScRs in aortas, with
      or without balloon injury, taken from hypercholesterolemic or
      normocholesterolemic rabbits. Numerous intimal cells in the rabbit aortic lesions
      expressed ScRs as detected by immunocytochemical staining with a goat anti-rabbit
      ScR antibody. Single immunostaining for cell identification markers in serial
      sections, as well as double staining, confirmed the expression of ScRs by both
      intimal smooth muscle cells and macrophages. To explore potential inducers of ScR
      expression by smooth muscle cells in vivo, we studied the regulation of ScR
      expression in vitro by cytokines known to be present in atherosclerotic lesions.
      Tumor necrosis factor-alpha (TNF-alpha) or interferon-gamma (IFN-gamma) increased
      ScR mRNA levels, protein expression, and AcLDL degradative activity in cultured
      rabbit aortic smooth muscle cells. The induction of ScR expression in intimal
      smooth muscle cells in vivo could be a useful marker of smooth muscle cell
      activation during atherogenesis and may contribute to foam cell formation by this
      cell type following balloon injury and/or hypercholesterolemia. Cytokines, such
      as TNF-alpha or IFN-gamma, may stimulate some of the phenotypic changes that
      characterize the alteration in gene expression of intimal smooth muscle cells in
      rabbit atherosclerotic lesions.

PMID- 7814606
TI  - The effect of oxytocin receptor blockade on parturition in guinea pigs.
AB  - The mechanism of the onset of labor is unknown in humans and guinea pigs.
      Contrary to most other species, progesterone withdrawal appears not to precede
      the onset of labor. To elucidate the role of oxytocin in the onset and
      maintenance of labor, guinea pigs were fitted with vascular catheters, an
      intraabdominal pressure catheter and an array of uterine electromyogram
      electrodes. An oxytocin antagonist (des-Gly9-[D-Trp2,Thr4,Orn8]dC6-oxytocin, 20
      micrograms/kg per h, n = 11) or saline solution (n = 12) was infused starting on
      day 66 of gestation (term is 69 d). Oxytocin receptor blockade resulted in
      decreased uterine activity and a prolonged expulsive phase (second stage) of
      labor. Fetal delivery was delayed and fetal mortality was increased. The onset of
      the expulsive phase of labor was delayed but maximum uterine activity occurred in
      time together with a timely change in uterine electromyogram activity from a
      prepartum to a postpartum pattern following an unaltered progressive increase in
      baseline uterine activity. This indicates that oxytocin is requisite for the
      normal progress of the first and second stage of labor, but has no involvement in
      the mechanism of the onset and the timing of labor.

PMID- 7814607
TI  - Chemokine expression during hepatic ischemia/reperfusion-induced lung injury in
      the rat. The role of epithelial neutrophil activating protein.
AB  - The liver is highly susceptible to a number of pathological insults, including
      ischemia/reperfusion injury. One of the striking consequences of liver injury is
      the associated pulmonary dysfunction that may be related to the release of
      hepatic-derived cytokines. We have previously employed an animal model of hepatic
      ischemia/reperfusion injury, and demonstrated that this injury causes the
      production and release of hepatic-derived TNF, which mediates a neutrophil
      dependent pulmonary microvascular injury. In this study, we have extended these
      previous observations to assess whether an interrelationship between TNF and the
      neutrophil chemoattractant/activating factor, epithelial neutrophil activating
      protein-78 (ENA-78), exists that may be accountable for the pathology of lung
      injury found in this model. In the context of hepatic ischemia/reperfusion
      injury, we demonstrated the following alterations in lung pathophysiology: (a) an
      increase in pulmonary microvascular permeability, lung neutrophil sequestration,
      and production of pulmonary-derived ENA-78; (b) passive immunization with
      neutralizing TNF antiserum resulted in a significant suppression of pulmonary
      derived ENA-78; and (c) passive immunization with neutralizing ENA-78 antiserum
      resulted in a significant attenuation of pulmonary neutrophil sequestration and
      microvascular permeability similar to our previous studies with anti-TNF. These
      findings support the notion that pulmonary ENA-78 produced in response to hepatic
      derived TNF is an important mediator of lung injury.

PMID- 7814608
TI  - Dual function of pneumolysin in the early pathogenesis of murine pneumococcal
      pneumonia.
AB  - Streptococcus pneumoniae is one of the most common etiologic agents of community
      acquired pneumonia, particularly bacteremic pneumonia. Pneumolysin, a
      multifunctional cytotoxin, is a putative virulence factor for S. pneumoniae;
      however, a direct role for pneumolysin in the early pathogenesis of pneumococcal
      pneumonia has not been confirmed in vivo. We compared the growth of a pneumolysin
      deficient (PLY[-]) type 2 S. pneumoniae strain with its isogenic wild-type strain
      (PLY[+]) after direct endotracheal instillation of bacteria into murine lungs.
      Compared with PLY(-) bacteria, infection with PLY(+) bacteria produced greater
      injury to the alveolar-capillary barrier, as assayed by albumin concentrations in
      alveolar lavage, and substantially greater numbers of PLY(+) bacteria were
      recovered in alveolar lavages and lung homogenates at 3 and 6 h after infection.
      The presence of pneumolysin also contributed to the development of bacteremia,
      which was detected at 3 h after intratracheal instillation of PLY(+) bacteria.
      The direct effects of pneumolysin on lung injury and on the ability of
      pneumococci to evade local lung defenses was confirmed by addition of purified
      recombinant pneumolysin to inocula of PLY(-) pneumococci, which promoted growth
      of PLY(-) bacteria in the lung to levels comparable to those seen with the PLY(+)
      strain. We further demonstrated the contributions of both the cytolytic and the
      complement-activating properties of pneumolysin on enhanced bacterial growth in
      murine lungs using genetically modified pneumolysin congeners and genetically
      complement-deficient mice. Thus, pneumolysin facilitates intraalveolar
      replication of pneumococci, penetration of bacteria from alveoli into the
      interstitium of the lung, and dissemination of pneumococci into the bloodstream
      during experimental pneumonia. Moreover, both the cytotoxic and the complement
      activating activities of pneumolysin may contribute independently to the acute
      pulmonary injury and the high rates of bacteremia which characterize pneumococcal
      pneumonia.

PMID- 7814609
TI  - 31P-nuclear magnetic resonance studies of chronic myocardial ischemia in the
      Yucatan micropig.
AB  - In this work, an x-irradiation/high fat/high cholesterol diet-induced atherogenic
      model was invoked to examine the effects of severe diffuse atherosclerosis on
      myocardial metabolism in the in vivo porcine heart. This model was studied using
      spatially localized 31P-nuclear magnetic resonance (NMR) to monitor pH and the
      levels of inorganic phosphate, phosphomonoesters, creatine phosphate, and
      adenosine triphosphate as a function of workload transmurally in control swine
      and in animals suffering from chronic ischemic heart disease. These preliminary
      studies revealed that the development of severe atherosclerosis and the
      accompanying chronically diseased state produce changes in high energy phosphates
      and that increases in rate pressure products result in demonstrable signs of
      ischemia in the myocardium which span the entire left ventricular wall. Ischemic
      changes include a global increase in inorganic phosphate and corresponding
      decreases in creatine phosphate, ATP, and pH. Importantly, changes in
      intracellular pH are noted with even the slightest increase in workload
      suggesting that these diseased hearts display elevated glycolytic activity. By
      challenging these animals with increased cardiac workload, we directly visualize
      how the chronically compromised heart responds to severe oxygen challenges in a
      clinically relevant model of this situation.

PMID- 7814610
TI  - Interaction between free fatty acids and insulin in the acute control of very low
      density lipoprotein production in humans.
AB  - Changes in VLDL triglyceride and VLDL apo B production were determined
      semiquantitatively in healthy young men by examining the effect of altering
      plasma insulin and/or FFA levels on the change in the slopes of the specific
      activity of VLDL [3H]triglyceride glycerol or the 131I-VLDL apo B versus time
      curves. In one study (n = 8) insulin was infused for 5 h using the euglycemic
      hyperinsulinemic clamp technique. Plasma FFA levels declined by approximately 80%
      (0.52 +/- 0.01 to 0.11 +/- 0.02 mmol/liter), VLDL triglyceride production
      decreased by 66.7 +/- 4.2% (P = 0.0001) and VLDL apo B production decreased by
      51.7 +/- 10.6% (P = 0.003). In a second study (n = 8) heparin and Intralipid
      (Baxter Corp., Toronto, Canada) were infused with insulin to prevent the insulin
      mediated fall in plasma FFA levels. Plasma FFA increased approximately twofold
      (0.43 +/- 0.05 to 0.82 + 0.13 mmol/liter), VLDL triglyceride production decreased
      to a lesser extent than with insulin alone (P = 0.006) (-31.8 +/- 9.5%, decrease
      from baseline P = 0.03) and VLDL apo B production did not decrease significantly
      (-6.3 +/- 13.6%, P = NS). In a third study (n = 8) when heparin and Intralipid
      were infused without insulin, FFA levels rose approximately twofold (0.53 +/-
      0.04 to 0.85 +/- 0.1 mmol/liter), VLDL triglyceride production increased by 180.1
      +/- 45.7% (P = 0.008) and VLDL apo B production increased by 94.2 +/- 28.7% (P =
      0.05). We confirm our previous observation that acute hyperinsulinemia suppresses
      VLDL triglyceride and VLDL apo B production in healthy humans. In addition, we
      have demonstrated that elevation of plasma FFA levels acutely stimulates VLDL
      production in vivo in healthy young males. Elevating plasma FFA during
      hyperinsulinemia attenuates but does not completely abolish the suppressive
      effect of insulin on VLDL production, at least with respect to VLDL
      triglycerides. Therefore, in normal individuals the acute inhibition of VLDL
      production by insulin in vivo is only partly due to the suppression of plasma
      FFA, and may also be due to an FFA-independent process.

PMID- 7814612
TI  - Use of 2H2O for estimating rates of gluconeogenesis. Application to the fasted
      state.
AB  - A method is introduced for estimating the contribution of gluconeogenesis to
      glucose production. 2H2O is administered orally to achieve 0.5% deuterium
      enrichment in body water. Enrichments are determined in the hydrogens bound to
      carbons 2 and 6 of blood glucose and in urinary water. Enrichment at carbon 6 of
      glucose is assayed in hexamethylenetetramine, formed from formaldehyde produced
      by periodate oxidation of the glucose. Enrichment at carbon 2 is assayed in
      lactate formed by enzymatic transfer of the hydrogen from glucose via sorbitol to
      pyruvate. The fraction gluconeogenesis contributes to glucose production equals
      the ratio of the enrichment at carbon 6 to that at carbon 2 or in urinary water.
      Applying the method, the contribution of gluconeogenesis in healthy subjects was
      23-42% after fasting 14 h, increasing to 59-84% after fasting 42 h. Enrichment at
      carbon 2 to that in urinary water was 1.12 +/- 0.13. Therefore, the assumption
      that hydrogen equilibrated during hexose-6-P isomerization was fulfilled. The
      3H/14C ratio in glucose formed from [3-3H,3-14C]lactate given to healthy subjects
      was 0.1 to 0.2 of that in the lactate. Therefore equilibration during
      gluconeogenesis of the hydrogen bound to carbon 6 with that in body water was 80
      90% complete, so that gluconeogenesis is underestimated by 10-20%. Glycerol's
      contribution to gluconeogenesis is not included in these estimates. The method is
      applicable to studies in humans of gluconeogenesis at safe doses of 2H2O.

PMID- 7814611
TI  - Downregulation of calcitonin receptor mRNA expression by calcitonin during human
      osteoclast-like cell differentiation.
AB  - Calcitonin inhibits both osteoclast formation and bone resorption, and is a
      primary treatment for patients with hypercalcemia and increased bone turnover.
      However, the clinical utility of calcitonin is limited because patients become
      refractory to calcitonin after several days (the calcitonin "escape phenomenon").
      The molecular basis for calcitonin "escape" is unclear. To determine the
      regulatory mechanisms controlling calcitonin receptor (CTR) expression in
      osteoclasts and their precursors, we treated immature mononuclear precursors for
      human osteoclast-like multinucleated cells (MNC) formed in vitro with 1,25
      (OH)2D3, to induce their differentiation to committed mononuclear precursors, and
      mature multinucleated osteoclasts, and used reverse transcriptase (RT)-PCR to
      assess expression of CTR mRNA in both committed mononuclear precursors and MNC.
      The PCR fragment produced was cloned and sequenced to confirm that it was derived
      from CTR mRNA. CTR mRNA expression was detected in mononuclear MNC precursors
      after 7 d of 1,25-(OH)2D3 treatment. It was also present in osteoclast-like MNC
      and highly purified giant cells from osteoclastomas, but not in monocytes or
      macrophage polykaryons formed in vitro. Calcitonin markedly decreased CTR but not
      actin mRNA expression in giant cells and MNC after 12 h, and removal of
      calcitonin restored CTR mRNA expression. Similarly, calcitonin decreased
      calcitonin-induced adenylate cyclase activity. These data suggest: (a)
      downregulation of CTR gene expression by calcitonin may in part explain the
      calcitonin "escape phenomenon"; and (b) expression of CTR mRNA occurs in
      mononuclear osteoclast precursors within 7 d after exposure to 1,25-(OH)2D3.

PMID- 7814613
TI  - Evidence for enhanced vascular superoxide anion production in nitrate tolerance.
      A novel mechanism underlying tolerance and cross-tolerance.
AB  - We sought to examine mechanisms underlying nitroglycerin (NTG) tolerance and
      "cross-tolerance" to other nitrovasodilators. Rabbits were treated for 3 d with
      NTG patches (0.4 mg/h) and their aortic segments studied in organ chambers.
      Relaxations were examined after preconstriction with phenylephrine. In NTG
      tolerant rabbit aorta, relaxations to cGMP-dependent vasodilators such as NTG (45
      +/- 6%), SIN-1 (69 +/- 7%), and acetylcholine (ACh, 64 +/- 5%) were attenuated
      vs. controls, (90 +/- 2, 94 +/- 3, and 89 +/- 2% respectively, P < 0.05 for all),
      while responses to the cAMP-dependent vasodilator forskolin remained unchanged.
      In tolerant aorta, endothelial removal markedly enhanced relaxations to NTG and
      SIN-1 (82 +/- 4 and 95 +/- 3%, respectively). Other studies were performed to
      determine how the endothelium enhances tolerance. Vascular steady state .-O2
      levels (assessed by lucigenin chemiluminescence) was increased twofold in
      tolerant vs. control vessels with endothelium (0.31 +/- 0.01 vs. 0.61 +/- 0.01
      nmol/mg per minute). This difference was less in vessels after denudation of the
      endothelium. Diphenylene iodonium, an inhibitor of flavoprotein containing
      oxidases, and Tiron a direct .-O2 scavenger normalized .-O2 levels. In contrast,
      oxypurinol (1 mM) an inhibitor of xanthine oxidase, rotenone (50 microM) an
      inhibitor of mitochondrial electron transport and NG-nitro-L-arginine (100
      microM) an inhibitor of nitric oxide synthase did not affect the
      chemiluminescence signals from NTG-tolerant aortas. Pretreatment of tolerant
      aorta with liposome-entrapped, pH sensitive superoxide dismutase (600 U/ml)
      significantly enhanced maximal relaxation in response to NTG, SIN-1, and ACh, and
      effectively reduced chemiluminescence signals. These studies show that continuous
      NTG treatment is associated with increased vascular .-O2-production and
      consequent inhibition of NO. mediated vasorelaxation produced by both exogenous
      and endogenous nitrovasodilators.

PMID- 7814614
TI  - In vitro fluid secretion by epithelium from polycystic kidneys.
AB  - The size of the kidneys in patients with autosomal dominant polycystic kidney
      disease (ADPKD) is due in large measure to the accumulation of secreted fluid
      within thin-walled epithelial sacs. We measured the net transepithelial movement
      of liquid in response to forskolin in isolated, intact cysts excised from the
      surface of human ADPKD kidneys and in cultured, polarized monolayers of
      epithelial cells derived from ADPKD cysts. 10 excised cysts bathed symmetrically
      in control culture medium secreted fluid at a rate of 0.19 +/- 0.03
      microliter/cm2 per hour after stimulation with forskolin (10 microM). Ouabain
      (100 microM) addition to the cavity fluid did not change the rate of fluid
      secretion of 10 forskolin-treated cysts, but addition of the glycoside to the
      external bathing medium fluid of nine cysts decreased secretion to -0.004 +/-
      0.05 microliter/cm2 per hour. 24 monolayers absorbed fluid (range -0.029 to 
      0.412 microliter/cm2 per hour); by contrast, fluid was secreted (range 0.074 to
      1.242 microliters/cm2 per hour) after stimulation with forskolin (10 microM).
      Ouabain (0.1 microM) in the basolateral but not in the apical medium inhibited
      fluid secretion. Forskolin increased the intracellular cyclic AMP content of
      ADPKD and MDCK monolayers by 236 and 196%, respectively. Six ADPKD monolayers had
      stable lumen negative transepithelial electrical potential differences (PDte) of 
      1.4 +/- 0.3 mV, positive short circuit currents (SCC) of 11.9 +/- 2.1
      microAmp/cm2 and a tissue resistance (Rte) of 116 +/- 14 ohm.cm2. Forskolin
      increased SCC to 15.5 +/- 1.9 microAmp/cm2 (P < 0.005) and decreased Rte to 95 +/
      13 ohm.cm2 (P < 0.05); PDte remained stable at -1.4 +/- 0.3 mV. Ouabain (10
      microM) had no effect when added to the apical medium, but in the basolateral
      medium decreased SCC to 1.7 +/- 0.3 microAmp/cm2 and PDte to -0.2 +/- 0.1 mV. We
      conclude that ADPKD cells in surface cysts have the potential to absorb or to
      secrete solutes and fluid. cAMP-mediated fluid secretion from the basolateral
      medium into the lumen of surface ADPKD cysts may be driven by anion transport.

PMID- 7814615
TI  - A cholesterol deficiency syndrome in humans.

PMID- 7814617
TI  - Regulation of G protein-coupled receptor kinase subtypes in activated T
      lymphocytes. Selective increase of beta-adrenergic receptor kinase 1 and 2.
AB  - Beta-adrenergic receptor kinase (beta ARK) is a serine-threonine kinase involved
      in the process of homologous desensitization of G-coupled receptors. beta ARK is
      a member of a multigene family, consisting of six known subtypes, also named G
      protein-coupled receptor kinases (GRK 1-6). In this study we investigated the
      expression of GRKs during the process of T cell activation, which is of
      fundamental importance in regulating immune responses. T cell activation was
      induced by exposing mononuclear leukocytes (MNL) to PHA and confirmed by
      tritiated thymidine incorporation measurement. A substantial increase of GRK
      activity (as measured by in vitro phosphorylation of rhodopsin) was found after
      48 h (331 +/- 80% of controls) and 72 h (347 +/- 86% of controls) of exposure to
      PHA. A threefold increase of beta ARK1 immunoreactivity was found in MNL exposed
      to PHA for 72 h. Persistent activation of protein kinase C (PKC) by 10 nM 12-O
      tetradecanoylphorbol-13-acetate (TPA) was able to increase beta ARK activity to
      the same extent as PHA, suggesting a PKC-mediated mechanism. The kinetic of beta
      adrenergic-stimulated cAMP production was substantially modified in TPA and PHA
      activated cells, indicating that the increased GRK activity resulted in an
      increased beta-adrenergic homologous desensitization. A three- to fourfold
      increase in GRK activity was also observed in a population of T cell blasts (>
      97% CD3+) exposed to PHA for 48-72 h. A significant increase in beta ARK1 and
      beta ARK2 mRNA expression was observed 48 h after mitogen stimulation, while mRNA
      expression of GRK5 and GRK6 was not changed. In conclusion our data show that the
      expression of GRK subtypes is actively and selectively modulated according to the
      functional state of T lymphocytes.

PMID- 7814616
TI  - Physiologic, metabolic, and muscle fiber type characteristics of musculus uvulae
      in sleep apnea hypopnea syndrome and in snorers.
AB  - Upper airway dilator muscles play an important role in the pathophysiology of
      sleep apnea hypopnea syndrome (SAHS). The mechanical and structural
      characteristics of these muscles remain unknown. The aim of this study was to
      compare the physiologic, metabolic, and fiber type characteristics of one upper
      airway dilator muscle (musculus uvulae, MU) in 11 SAHS and in seven nonapneic
      snorers. The different analyses were done on MU obtained during uvulo-palato
      pharyngoplasty. Snorers and SAHS differed only in their apnea + hypopnea indices
      (11.5 +/- 5.9 and 34.2 +/- 14.6/h, respectively, mean +/- SD). Absolute twitch
      and tetanic tension production of MU was significantly greater in SAHS than in
      snorers while the fatigability index was similar in the two groups. Protein
      content and anaerobic enzyme activities of MU were significantly greater in SAHS
      than in snorers; no difference was observed for aerobic enzyme activities. The
      total muscle fiber cross-sectional area of MU was significantly higher in SAHS
      (2.2 +/- 0.9 mm2) than in snorers (1.1 +/- 0.7 mm2). The surface occupied by type
      IIA muscle fibers of MU was larger in SAHS (2.00 +/- 0.96) than in snorers (0.84
      +/- 0.63 mm2). We conclude that the capacity for tension production and the
      anaerobic metabolic activity of MU are greater in SAHS than in snorers.

PMID- 7814618
TI  - Granulocyte macrophage colony-stimulating factor contributes to enhanced monocyte
      survival in chronic atopic dermatitis.
AB  - Evidence suggesting that prolonged effector cell survival may contribute to
      perpetuation of inflammation prompted us to ask whether monocyte macrophages, the
      predominate inflammatory cell in the lesion of chronic atopic dermatitis (AD),
      exhibit enhanced survival in AD. Cultures of peripheral blood monocytes from
      patients with chronic AD, psoriasis, and from normal (NL) donors were examined
      for morphologic features and DNA fragmentation characteristic of cells undergoing
      the process of apoptosis (programmed cell death). Cultures of AD monocytes
      exhibited a significantly lower incidence of apoptosis than did cultures of NL
      monocytes (45 vs 68%, P < 0.01), or psoriatic monocytes (45 vs 80%, P < 0.01).
      Furthermore, AD monocytes were unresponsive to both IL-1, an inhibitor of
      apoptosis, and IL-4, an enhancer of apoptosis, in comparison to cultured NL
      monocytes. Of note, GM-CSF in a concentration-dependent fashion, decreased the
      incidence of apoptosis in NL monocyte cultures and rendered them unresponsive to
      these cytokines. These findings suggested that GM-CSF may enhance monocyte
      survival in AD. In support of this hypothesis, AD monocyte cultures produced
      fivefold more GM-CSF than did cultures of NL monocytes or psoriatic monocytes (P
      < 0.05). Additionally, there was a significantly greater number of GM-CSF mRNA
      expressing cells detected by in situ hybridization in biopsies of lesions of
      chronic AD than in acute AD or NL skin (P < 0.05). Finally, NL monocytes
      incubated with supernatants obtained from monocytes of AD patients exhibited
      significant inhibition of apoptosis, an effect that could be ablated by a
      neutralizing antibody to GM-CSF. Taken together, these data strongly suggest that
      increased production of GM-CSF by cells from patients with AD inhibits monocyte
      apoptosis and may contribute to the chronicity of this inflammatory disease.

PMID- 7814619
TI  - De novo synthesis and secretion of a 36-kD protein by cells that form lupus
      inclusions in response to alpha-interferon.
AB  - In response to the pure recombinant human alpha-IFN, IFLrA, Raji and Daudi were
      the only two cell lines among 19 human lymphoblastoid cell lines tested that
      formed the human lupus inclusions (LI) to a high frequency. Raji, Daudi, and five
      other cell lines were examined for protein changes that might accompany LI
      formation. Their selection was based upon T or B origin, association with Epstein
      Barr virus, and ability to form LI. A trace protein of an estimated molecular
      mass of 36 kD (p36) and an isoelectric point of 5.6 was detected on two
      dimensional gels only of alpha-IFN-treated Raji and Daudi cells. Gamma-IFN did
      not induce p36 or LI in any of these seven cell lines. In Daudi cells p36 and LI
      formed simultaneously in response to IFLrA, and persisted until the alpha-IFN
      induced death of the culture. In Raji cells, p36 and LI appearance and
      disappearance coincided with the addition and removal of alpha-IFN. Fractionation
      of Raji cells with nonionic-detergent buffer placed p36 with the inclusions in
      the cytoplasmic supernatant. With detergent-free buffer p36 and LI were
      distributed evenly between the nuclear and cytoplasmic fractions. Pulse-chase
      experiments revealed that p36 was secreted. The de novo synthesis of p36 with
      alpha-IFN treatment was shown by labeling the cell proteins with [35S] methionine
      before and after the addition of alpha-IFN. These results along with previous
      results on the de novo synthesis of LI in the endoplasmic reticulum (which is
      involved in the processing and secretion of proteins) suggest a role for LI in
      the synthesis and secretion of p36.

PMID- 7814620
TI  - Shifts in the concentrations of magnesium and calcium in early porcine and rat
      wound fluids activate the cell migratory response.
AB  - Accruing evidence indicates that the levels of extracellular Mg2+ and Ca2+ can
      have a distinct impact on the adhesive and migratory activities of many cell
      types. The physiological relevance of these observations, however, has remained
      largely unexplored. In the present study, wound fluids collected throughout the
      early stages of cutaneous wound repair were examined for possible Mg2+ and Ca2+
      fluctuations. Early in the process, when cell migration into the wound site is
      initiated, Mg2+ is elevated and Ca2+ is reduced (Mg2+:Ca2+ = 1). As wound healing
      progresses, wound fluid concentrations of Mg2+ and Ca2+ begin to return to normal
      plasma levels (Mg2+:Ca2+ = 0.4). When macrophages, keratinocytes, fibroblasts,
      and endothelial cells were exposed to dialyzed wound fluid, the migration
      stimulated by undialyzed wound fluid was lost. Addition back to dialyzed wound
      fluid of 24 h, postinjury concentrations of Mg2+ and Ca2+ restored all migratory
      stimulus. This observed migration is approximately twofold greater than when
      normal plasma Mg2+ and Ca2+ concentrations are present. Changes in the levels of
      Mg2+ and Ca2+ in wound fluid occur during the same period that inflammatory
      cells, keratinocytes, fibroblasts, and neovasculature have been shown to migrate
      during wound healing in vivo. Together, these data suggest that the impact of
      these changes on integrins and E-cadherin may play a direct role in the
      activation and maintenance of the migratory phenotypes of the cells involved in
      the wound healing process.

PMID- 7814621
TI  - Mutations in the glucose-6-phosphatase gene are associated with glycogen storage
      disease types 1a and 1aSP but not 1b and 1c.
AB  - Glycogen storage disease (GSD) type 1, which is caused by the deficiency of
      glucose-6-phosphatase (G6Pase), is an autosomal recessive disease with
      heterogenous symptoms. Two models of G6Pase catalysis have been proposed to
      explain the observed heterogeneities. The translocase-catalytic unit model
      proposes that five GSD type 1 subgroups exist which correspond to defects in the
      G6Pase catalytic unit (1a), a stabilizing protein (1aSP), the glucose-6-P (1b),
      phosphate/pyrophosphate (1c), and glucose (1d) translocases. Conversely, the
      conformation-substrate-transport model suggests that G6Pase is a single
      multifunctional membrane channel protein possessing both catalytic and substrate
      (or product) transport activities. We have recently demonstrated that mutations
      in the G6Pase catalytic unit cause GSD type 1a. To elucidate whether mutations in
      the G6Pase gene are responsible for other GSD type 1 subgroups, we characterized
      the G6Pase gene of GSD type 1b, 1c, and 1aSP patients. Our results show that the
      G6Pase gene of GSD type 1b and 1c patients is normal, consistent with the
      translocase-catalytic unit model of G6Pase catalysis. However, a mutation in exon
      2 that converts an Arg at codon 83 to a Cys (R83C) was identified in both G6Pase
      alleles of the type 1aSP patient. The R83C mutation was also demonstrated in one
      homozygous and five heterogenous GSD type 1a patients, indicating that type 1aSP
      is a misclassification of GSD type 1a. We have also analyzed the G6Pase gene of
      seven additional type 1a patients and uncovered two new mutations that cause GSD
      type 1a.

PMID- 7814622
TI  - Cytotoxic and proliferative T cell responses in HIV-1-infected Macaca nemestrina.
AB  - Macaca nemestrina has been described as an animal model for acute HIV-1
      infection. This animal, unlike most infected humans, appears to contain HIV-1
      replication. Therefore analysis of HIV-1-specific proliferative and cytotoxic T
      lymphocyte (CTL) responses following HIV-1 challenge of M. nemestrina may provide
      information into the role of such responses in both the control of acute HIV
      infection and protective immunity. Although CD4+ T cell responses to HIV-1 are
      generally difficult to detect in HIV-1-infected humans, early and persistent CD4+
      T cell proliferative responses to HIV-1 antigens were detected in all HIV-1
      inoculated M. nemestrina. HIV-1-specific CD8+ CTL responses were evaluated in
      PBMC by stimulation with autologous cells expressing HIV-1 genes, limiting
      dilution precursor frequency analysis, and T cell cloning. CTL reactive with gag,
      env, and nef were present 4-8 wk after infection, and persisted to 140 wk after
      infection. The presence of both CD4+ and CD8+ T cell responses before and after
      clearance of HIV-1 viremia is consistent with a role for these responses in the
      successful control of HIV-1 viral replication observed in M. nemestrina. Further
      studies of T cell immunity in these animals that resist disease should provide
      insights into the immunobiology of HIV-1 infection.

PMID- 7814623
TI  - Mutations in human cytomegalovirus UL97 gene confer clinical resistance to
      ganciclovir and can be detected directly in patient plasma.
AB  - Specific mutations in the UL97 region of human cytomegalovirus (HCMV) have been
      found to confer resistance to laboratory-adapted strains subjected to ganciclovir
      selection. In this study, mutations in the UL97 region of HCMV isolates obtained
      from patients receiving ganciclovir therapy were examined to determine whether
      they would confer ganciclovir resistance, and if these mutations could be
      detected directly in the plasma of AIDS patients with progressive HCMV disease
      despite ganciclovir treatment. A single nucleotide change within a conserved
      region of UL97 was found in five resistant isolates, resulting in an amino acid
      substitution in residue 595: from leucine to phenylalanine in one, and from
      leucine to serine in four resistant isolates. A sixth resistant isolate
      demonstrated a single nucleotide change, leading to a threonine to isoleucine
      substitution in residue 659. The role of the 595 amino acid substitution in
      conferring ganciclovir resistance was confirmed by marker transfer experiments.
      In further studies, direct sequencing of HCMV DNA present in plasma obtained from
      persons with resistant viruses revealed the identical amino acid substitutions in
      plasma as those present in the cultured viruses. These findings indicate that
      clinical resistance to ganciclovir can result from specific point mutations in
      the UL97 gene, and that the emergence of the resistant genotype can be detected
      directly in patient plasma.

PMID- 7814624
TI  - Virus-induced airway hyperresponsiveness in guinea pigs is related to a
      deficiency in nitric oxide.
AB  - Intratracheal inoculation of parainfluenza type 3 virus to guinea pigs induces a
      marked increase in airway responsiveness in vivo and in vitro. In spontaneously
      breathing anesthetized guinea pigs inhalation of an aerosol containing the nitric
      oxide (NO) precursor L-arginine (2.0 mM) completely prevented the virus-induced
      airway hyperresponsiveness to histamine. In addition, perfusion of L-arginine
      (200 microM) or the direct NO-donor S-nitroso-N-acetyl-penicillamine (SNAP, 1
      microM) through the lumen of tracheal tubes from infected animals prevented the
      increase in airway responsiveness to histamine or the cholinoceptor agonist
      methacholine. The NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L
      NAME, 120 microM) did not further increase the virus-induced airway
      hyperresponsiveness. In additional experiments, NO was measured with an Iso-NO
      nitric oxide meter and sensor. Stimulation of control tissues in vitro with
      histamine (10(-3) M) resulted in a contraction with a simultaneous release of NO
      (44.5 +/- 5.4 nM). The release of NO was markedly reduced by 75% (P < 0.01, 11.4
      +/- 3.1 nM) in tracheas from virus-infected animals that demonstrated enhanced
      contractile responses. Preincubation of tissues from virus-treated guinea pigs
      with L-arginine (200 microM) completely prevented the enhanced contraction and
      simultaneously returned the NO production to control values (51.2 +/- 3.4 nM). An
      NO deficiency might be causally related to the development of airway
      hyperresponsiveness after a viral respiratory infection.

PMID- 7814625
TI  - Glutamine: a major gluconeogenic precursor and vehicle for interorgan carbon
      transport in man.
AB  - To compare glutamine and alanine as gluconeogenic precursors, we simultaneously
      measured their systemic turnovers, clearances, and incorporation into plasma
      glucose, their skeletal muscle uptake and release, and the proportion of their
      appearance in plasma directly due to their release from protein in postabsorptive
      normal volunteers. We infused the volunteers with [U-14C] glutamine, [3-13C]
      alanine, [2H5] phenylalanine, and [6-3H] glucose to isotopic steady state and
      used the forearm balance technique. We found that glutamine appearance in plasma
      exceeded that of alanine (5.76 +/- 0.26 vs. 4.40 +/- 0.33 mumol.kg-1.min-1, P <
      0.001), while alanine clearance exceeded glutamine clearance (14.7 +/- 1.3 vs.
      9.3 +/- 0.8 ml.kg-1.min-1, P < 0.001). Glutamine appearance in plasma directly
      due to its release from protein was more than double that of alanine (2.45 +/-
      0.25 vs. 1.16 +/- 0.12 mumol.kg-1.min-1, P < 0.001). Although overall carbon
      transfer to glucose from glutamine and alanine was comparable (3.53 +/- 0.24 vs
      3.47 +/- 0.32 atoms.kg-1.min-1), nearly twice as much glucose carbon came from
      protein derived glutamine than alanine (1.48 +/- 0.15 vs 0.88 +/- 0.09 atoms.kg
      1.min-1, P < 0.01). Finally, forearm muscle released more glutamine than alanine
      (0.88 +/- 0.05 vs 0.48 +/- 0.05 mumol.100 ml-1.min-1, P < 0.01). We conclude that
      in postabsorptive humans glutamine is quantitatively more important than alanine
      for transporting protein-derived carbon through plasma and adding these carbons
      to the glucose pool.

PMID- 7814627
TI  - Endogenous adenosine mediates coronary vasodilation during exercise after K(ATP)+
      channel blockade.
AB  - The mechanism of coronary vasodilation produced by exercise is not understood
      completely. Recently, we reported that blockade of vascular smooth muscle K(ATP)+
      channels decreased coronary blood flow at rest, but did not attenuate the
      increments in coronary flow produced by exercise. Adenosine is not mandatory for
      maintaining basal coronary flow, or the increase in flow produced by exercise
      during normal arterial inflow, but does contribute to coronary vasodilation in
      hypoperfused myocardium. Therefore, we investigated whether adenosine opposed the
      hypoperfusion produced by K(ATP)+ channel blockade, thereby contributing to
      coronary vasodilation during exercise. 11 dogs were studied at rest and during
      exercise under control conditions, during intracoronary infusion of the K(ATP)+
      channel blocker glibenclamide (50 micrograms/kg per min), and during
      intracoronary glibenclamide in the presence of adenosine receptor blockade.
      Glibenclamide decreased resting coronary blood flow from 45 +/- 5 to 35 +/- 4
      ml/min (P < 0.05), but did not prevent exercise-induced increases of coronary
      flow. Glibenclamide caused an increase in myocardial oxygen extraction at the
      highest level of exercise with a decrease in coronary venous oxygen tension from
      15.5 +/- 0.7 to 13.6 +/- 0.8 mmHg (P < 0.05). The addition of the adenosine
      receptor antagonist 8-phenyltheophylline (5 mg/kg intravenous) to K(ATP)+ channel
      blockade did not further decrease resting coronary blood flow but did attenuate
      the increase in coronary flow produced by exercise. This was accompanied by a
      further decrease of coronary venous oxygen tension to 10.1 +/- 0.7 mmHg (P <
      0.05), indicating aggravation of the mismatch between oxygen demand and supply.
      These findings are compatible with the hypothesis that K+ATP channels modulate
      coronary vasomotor tone both under resting conditions and during exercise.
      However, when K(ATP)+ channels are blocked, adenosine released from the
      hypoperfused myocardium provides an alternate mechanism to mediate coronary
      vasodilation in response to increases in oxygen demand produced by exercise.

PMID- 7814626
TI  - Pathway of free fatty acid oxidation in human subjects. Implications for tracer
      studies.
AB  - To determine the pathway of plasma FFA oxidation and the site(s) of label
      fixation observed during infusion of FFA tracers, [1-13C]palmitate and [1
      14C]acetate were infused intravenously for 3 h in five volunteers. Breath 13CO2
      enrichment and 14CO2 specific activity were followed for 6 h to determine the
      labeled CO2 decay rates. Acetate enters directly into the TCA cycle; hence, if
      palmitate transits a large lipid pool before oxidation, 13CO2 enrichment (from
      palmitate) should decay slower than 14CO2 specific activity (from acetate).
      Breath 13CO2 enrichment and 14CO2 specific activity decayed at a similar rate
      after stopping the tracer infusions (half-lives of 13CO2 and 14CO2 decay: mean
      [+/- SE] 106.6 +/- 8.9 min, and 96.9 +/- 6.0 min, respectively, P = NS), which
      suggests that palmitate enters the TCA cycle directly and that label fixation
      occurs after citrate synthesis. Significant label fixation was shown in plasma
      glutamate/glutamine and lactate/pyruvate during infusion of either [1,2
      13C]acetate or [U-13C]palmitate, suggesting that TCA cycle exchange reactions are
      at least partly responsible for label fixation. This was consistent with our
      finding that the half-lives of 13CO2 enrichment and 14CO2 specific activity
      decreased significantly during exercise to 14.4 +/- 3 min and 16.8 +/- 1 min,
      respectively, since exercise significantly increases the rate of the TCA cycle in
      relation to that of the TCA cycle exchange reactions. We conclude that plasma FFA
      entering cells destined to be oxidized are directly oxidized and that tracer
      estimates of plasma FFA oxidation will underestimate the true value unless
      account is taken of the extent of label fixation.

PMID- 7814628
TI  - Cellular and molecular basis of human gamma delta T cell activation. Role of
      accessory molecules in alloactivation.
AB  - Although gamma delta T cell receptor-bearing lymphocytes (gamma delta T cells)
      constitute a significant minority of circulating and tissue-associated T
      lymphocytes, the mechanism responsible for the activation of these cells is
      unknown. To address this question, resting gamma delta TCR+, CD3+, CD4-, CD8-
      cells isolated from the blood of healthy volunteers were cultured with allogeneic
      dendritic cells (DC) or monocytes, and their proliferative response measured. DC
      alone induced gamma delta T cells to proliferate, with a peak response on the
      sixth day of culture. Pretreatment of DC with an anti-HLA-DR mAb, but not anti
      HLA class I or anti-CD1 mAbs, inhibited the response of gamma delta T cells.
      Antibodies to gamma delta T cell receptor, CD2, CD3, or CD11a were also
      inhibitory, whereas antibodies to alpha beta T cell receptor, CD4, CD5, and CD8
      had no effect. Although only 40-60% of freshly isolated gamma delta T cells
      expressed CD28, mAbs directed against CD28 or its ligand, CD80, were markedly
      inhibitory. Moreover, removal of CD28+ cells from the gamma delta T cell
      population nearly abrogated the response to DC. These results demonstrate that
      resting gamma delta T cells recognize and respond to MHC class II determinants on
      allogeneic DC in a manner that is highly dependent on the CD28 activation pathway
      as well as molecules such as CD2 and CD11a that mediate cell-to-cell adhesion.

PMID- 7814629
TI  - Clinical implications of the stress response.
AB  - A field of research that began with a curious observation in Drosophila has
      resulted in a new understanding of how cells respond to sudden and adverse
      changes in their environment. In addition through the study of the
      structure/function of the stress proteins, especially those which function as
      molecular chaperones, new insights into the details by which proteins are
      synthesized and acquire their final biologically active conformation have been
      realized. Equally exciting is the progress being made as it relates the potential
      diagnostic and therapeutic applications of the stress-response proteins. The use
      of stress proteins as the next generation of vaccines and/or their use as
      potentially powerful adjuvants, capable of stimulating both T and B cell
      responses to a particular antigen of interest appear close to becoming a reality.
      One wonders how many more surprises are in store for us as we continue to explore
      this evolutionally conserved cellular stress response.

PMID- 7814630
TI  - Differential regulation of renal phospholipase C isoforms by catecholamines.
AB  - Dopamine and D1 agonists and NE all increase phosphatidyl inositol-specific
      phospholipase C (PLC) activity, but whereas dopamine produces a natriuresis, NE
      has an antinatriuretic effect. To determine if catecholamines differentially
      regulate the expression of PLC isoforms, we infused fenoldopam, a D1 agonist, or
      pramipexole, a D1/D2 agonist, intravenously or infused fenoldopam or NE into the
      renal artery of anesthetized rats. After 3-4 h of infusion, when the expected
      natriuresis (fenoldopam or pramipexole) or antinatriuresis (NE) occurred, the
      kidneys were removed for analysis of PLC isoform protein expression activity.
      Western blot analysis revealed that in renal cortical membranes, fenoldopam and
      pramipexole increased expression of PLC beta 1 and decreased expression of PLC
      gamma 1; PLC delta was unchanged. In the cytosol, pramipexole and fenoldopam
      increased expression of both PLC beta 1 and PLC gamma 1. No effects were noted in
      the medulla. A preferential D1 antagonist, SKF 83742, which by itself had no
      effect, blocked the effects of pramipexole, thus confirming the involvement of
      the D1 receptor. In contrast, NE also increased PLC beta 1 but did not affect PLC
      gamma 1 protein expression in membranes. The changes in PLC isoform expression
      were accompanied by similar changes in PLC isoform activity. These studies
      demonstrate for the first time differential regulation of PLC isoforms by
      catecholamines.

PMID- 7814631
TI  - On the role of phosphatidylethanolamine in the inhibition of activated protein C
      activity by antiphospholipid antibodies.
AB  - Phosphatidylethanolamine (PE) is an important membrane component for supporting
      activated protein C anticoagulant activity but has little influence on
      prothrombin activation. This difference constitutes a potential mechanism for
      selective inhibition of the protein C anticoagulant pathway by lupus
      anticoagulants and/or antiphospholipid antibodies. In this study, we demonstrate
      that the presence of PE augments lupus anticoagulant activity. In the plasma of
      some patients with lupus anticoagulants, activated protein C anticoagulant
      activity is more potently inhibited than prothrombin activation. As a result, in
      the presence of activated protein C and PE, these patient plasmas clot faster
      than normal plasma. Patients with minimal lupus anticoagulant activity are
      identified whose plasma potently inhibits activated protein C anticoagulant
      activity. This process is also PE dependent. In three patient plasmas, these
      phenomena are shown to be due to immunoglobulins. The PE requirement in the
      expression of activated protein C anticoagulant activity and the PE dependence of
      some antiphospholipid antibodies provide a mechanistic basis for the selective
      inhibition of the protein C pathway. Inhibition of activated protein C function
      may be a common mechanism contributing to increased thrombotic risk in certain
      patients with antiphospholipid antibodies.

PMID- 7814632
TI  - Regulation of biliary lipid secretion by mdr2 P-glycoprotein in the mouse.
AB  - Disruption of the mdr2 gene in mice leads to a complete absence of phospholipid
      from bile (Smit, J. J. M., et al. 1993. Cell. 75:451-462). We have investigated
      the control of both mdr2 P-glycoprotein (Pgp) expression and bile salt secretion
      on biliary lipid secretion in the mouse. Lipid secretion was monitored at various
      bile salt output rates in wild-type mice (+/+), heterozygotes (+/-), and
      homozygotes (-/-) for mdr2 gene disruption. In (-/-) mice, phospholipid secretion
      was negligible at all bile salt output rates. In (+/-) mice, a curvilinear
      relation between bile salt and phospholipid secretion was observed similar to
      that in (+/+) mice; however, at all bile salt secretion rates phospholipid
      secretion was reduced compared to (+/+) mice, indicating that mdr2 Pgp exerts a
      strong control over secretion. Infusion of increasing amounts of taurocholate up
      to maximal secretory rate led to a decline in the phospholipid and cholesterol
      secretion in both (+/+) and (+/-) mice in accordance to what has been observed in
      other species. In contrast, in (-/-) mice cholesterol secretion increased under
      these conditions while phospholipid output remained extremely low. The increased
      cholesterol secretion may represent extraction of cholesterol from the
      canalicular plasma membrane by taurocholate micelles as opposed to the
      concomitant secretion of both phospholipid and cholesterol in the presence of a
      functional mdr2 Pgp. Increased bile flow in (-/-) mice could be attributed
      completely to an increase in the bile salt-independent fraction and may therefore
      be caused by the bile duct proliferation in these mice.

PMID- 7814633
TI  - Tat-independent replication of human immunodeficiency viruses.
AB  - The replication of human immunodeficiency retroviruses involves a complex series
      of events that is regulated at both transcriptional and posttranscriptional
      levels. The tat gene product is a potent trans-activator of viral transcription
      and therefore an attractive target for the development of antiviral drugs. Tat
      defective HIV-1 proviral DNA clones have been shown previously to be replication
      defective. In this study, we report that tat-defective HIV-1 and HIV-2 viral DNA
      transfected into U937 cells can direct efficient viral replication in the
      presence of transcriptional stimulators such as TNF-alpha and PMA. In MT-4 cells,
      tat-defective HIV-1 can replicate without any stimulation. The viruses recovered
      from MT-4 cells remained tat defective defined by their inability to infect T
      cell lines (e.g., Molt 4/8) although replication could be rescued with cytokines.
      Limited replication was observed in primary mononuclear cells. Furthermore, we
      showed that Ro 24-7429, a potent tat antagonist and antiviral compound, failed to
      suppress HIV-1 replication in TNF-alpha-stimulated T cells. These results have
      important implications for targeting tat as a therapeutic strategy for AIDS.

PMID- 7814634
TI  - Patients with congenital myasthenia associated with end-plate
      acetylcholinesterase deficiency show normal sequence, mRNA splicing, and assembly
      of catalytic subunits.
AB  - A congenital myasthenic condition has been described in several patients
      characterized by a deficiency in end-plate acetylcholinesterase (AChE). The
      characteristic form of AChE in the end-plate basal lamina has the catalytic
      subunits disulfide linked to a collagen-like tail unit. Southern analysis of the
      gene encoding the catalytic subunits revealed no differences between patient and
      control DNA. Genomic DNA clones covering exon 4 and the alternatively spliced
      exons 5 and 6 were analyzed by nuclease protection and sequencing. Although
      allelic differences were detected between controls, we found no differences in
      exonic and intronic areas that might yield distinctive splicing patterns in
      patients and controls. The ACHE gene was cloned from genomic libraries from a
      patient and a control. Transfection of the cloned genes revealed identical
      species of mRNA and expressed AChE. Cotransfection of the genes expressing the
      catalytic subunits with a cDNA from Torpedo encoding the tail unit yielded
      asymmetric species that require assembly of catalytic subunits and tail unit.
      thus the catalytic subunits of AChE expressed in the congenital myasthenic
      syndrome appear identical in sequence, arise from similar splicing patterns, and
      assemble normally with a tail unit to form a heteromeric species.

PMID- 7814635
TI  - Development of a lipopeptide-based therapeutic vaccine to treat chronic HBV
      infection. I. Induction of a primary cytotoxic T lymphocyte response in humans.
AB  - Our goal is to use peptide epitopes that are recognized by cytotoxic T
      lymphocytes (CTL) as immunogens for the development of prophylactic and
      therapeutic vaccines with chronic hepatitis B virus (HBV) infection being our
      first therapeutic target. Because most CTL peptide epitopes are poor immunogens,
      we specifically modified them by covalently attaching two additional components:
      a T helper peptide epitope and two lipid molecules. Using the murine influenza
      virus CTL epitope NP 147-155 as a model system, we found this construct to be
      highly immunogenic, and a single injection resulted in memory CTL induction that
      persisted for > 1 yr. Based on the animal studies, a vaccine was designed and
      tested for both safety and its ability to induce a primary CTL response in normal
      subjects. The three vaccine components included HBV core antigen peptide 18-27 as
      the CTL epitope, tetanus toxoid peptide 830-843 as the T helper peptide, and two
      palmitic acid molecules as the lipids. A dose escalation trial (5, 50, and 500
      micrograms) carried out in 26 normal subjects showed that the vaccine was safe
      and able to induce a primary HBV-specific CTL response. A dose-response curve was
      observed and five out of five subjects responded to the 500-micrograms dose.

PMID- 7814636
TI  - Crucial residues in the carboxy-terminal end of C1 inhibitor revealed by
      pathogenic mutants impaired in secretion or function.
AB  - The last exon of the C1-1NH gene was screened for point mutations in 36 unrelated
      hereditary angioedema patients. Mutations were found in eight patients,
      predicting changes in the short COOH-terminal region which anchors the reactive
      site loop on its COOH-terminal side. The effects of each of these mutations were
      examined in transiently transfected Cos-7 cells. Complete intracellular retention
      or degradation was observed with substitutions in the COOH-terminal strands 4B or
      5B: Leu459-->Pro, Leu459-->Arg, and Pro467-->Arg were all blocked at early stages
      of intracellular transport, but differences in the immunofluorescence patterns
      indicated that a significant fraction of the Leu459-->Pro and of the Pro467-->Arg
      proteins reached a compartment distinct from the endoplasmic reticulum. In line
      with previous findings with alpha 1-antitrypsin, chain termination within strand
      5B resulted in rapid degradation. Mutant Val451-->Met, in strand 1C, and mutant
      Pro476-->Ser, replacing the invariant proline near the COOH terminus, yielded
      reduced secretion, but these extracellular proteins were unable to bind the
      target protease C1s. Presence of low levels of both dysfunctional proteins in
      patient plasmas defies the conventional classification of C1 inhibitor
      deficiencies as type I or type II. These data point to a key role of certain
      residues in the conserved COOH-terminal region of serpins in determining the
      protein foldings compatible with transport and proper exposure of the reactive
      site loop.

PMID- 7814637
TI  - Inhibition of cytoplasmic and organellar protein synthesis in Toxoplasma gondii.
      Implications for the target of macrolide antibiotics.
AB  - We investigated potential targets for the activity of protein synthesis
      inhibitors against the protozoan parasite Toxoplasma gondii. Although nanomolar
      concentrations of azithromycin and clindamycin prevent replication of T. gondii
      in both cell culture and in vivo assays, no inhibition of protein labeling was
      observed in either extracellular or intracellular parasites treated with up to
      100 microM drug for up to 24 h. Quantitative analysis of > 300 individual spots
      on two-dimensional gels revealed no proteins selectively depleted by 100 microM
      azithromycin. In contrast, cycloheximide inhibited protein synthesis in a dose
      dependent manner. Nucleotide sequence analysis of the peptidyl transferase region
      from genes encoding the large subunit of the parasite's ribosomal RNA predict
      that the cytoplasmic ribosomes of T. gondii, like other eukaryotic ribosomes,
      should be resistant to macrolide antibiotics. Combining cycloheximide treatment
      with two-dimensional gel analysis revealed a small subset of parasite proteins
      likely to be synthesized on mitochondrial ribosomes. Synthesis of these proteins
      was inhibited by 100 microM tetracycline, but not by 100 microM azithromycin or
      clindamycin. Ribosomal DNA sequences believed to be derived from the T. gondii
      mitochondrial genome predict macrolide/lincosamide resistance. PCR amplification
      of total T. gondii DNA identified an additional class of prokaryotic-type
      ribosomal genes, similar to the plastid-like ribosomal genes of the Plasmodium
      falciparum. Ribosomes encoded by these genes are predicted to be sensitive to the
      lincosamide/macrolide class of antibiotics, and may serve as the functional
      target for azithromycin, clindamycin, and other protein synthesis inhibitors in
      Toxoplasma and related parasites.

PMID- 7814638
TI  - Fibroblast growth factor stimulates angiotensin converting enzyme expression in
      vascular smooth muscle cells. Possible mediator of the response to vascular
      injury.
AB  - Angiotensin converting enzyme (ACE) activity contributes to the vascular response
      to injury because ACE inhibition limits neointima formation in rat carotid
      arteries after balloon injury. To investigate the mechanisms by which ACE may
      contribute to vascular smooth muscle cell (VSMC) proliferation, we studied
      expression of ACE in vivo after injury and in vitro after growth factor
      stimulation. ACE activity 14 d after injury was increased 3.6-fold in the injured
      vessel. ACE expression, measured by immunohistochemistry, became apparent at 7 d
      in the neointima and at 14 d was primarily in the most luminal neointimal cells.
      To characterize hormones that induce ACE in vivo, cultured VSMC were exposed to
      steroids and growth factors. Among steroids, only glucocorticoids stimulated ACE
      expression with an 8.0 +/- 2.1-fold increase in activity and a 6.5-fold increase
      in mRNA (30 nM dexamethasone for 72 h). Among growth factors tested, only
      fibroblast growth factor (FGF) stimulated ACE expression (4.2 +/- 0.7-fold
      increase in activity and 1.6-fold increase in mRNA in response to 10 ng/ml FGF
      for 24 h). Dexamethasone and FGF were synergistic at the indicated concentrations
      inducing 50.6 +/- 12.4-fold and 32.5-fold increases in activity and mRNA
      expression, respectively. In addition, when porcine iliac arteries were
      transfected with recombinant FGF-1 (in the absence of injury), ACE expression
      increased in neointimal VSMC, to the same extent as injured, nontransfected
      arteries. The data suggest a temporal sequence for the response to injury in
      which FGF induces ACE, ACE generates angiotensin II, and angiotensin II
      stimulates VSMC growth in concert with FGF.

PMID- 7814639
TI  - Late preconditioning against myocardial stunning. An endogenous protective
      mechanism that confers resistance to postischemic dysfunction 24 h after brief
      ischemia in conscious pigs.
AB  - Conscious pigs underwent a sequence of 10 2-min coronary occlusions, each
      separated by 2 min of reperfusion, for three consecutive days (days 1, 2, and 3
      of stage I). The recovery of systolic wall thickening (WTh) after the 10th
      reperfusion was markedly improved on days 2 and 3 compared with day 1, indicating
      that the myocardium had become preconditioned against "stunning." 10 d after
      stage I, pigs underwent again a sequence of 10 2-min coronary occlusions for two
      consecutive days (days 1 and 2 of stage II). On day 1 of stage II, the recovery
      of WTh after the 10th reperfusion was similar to that noted on day 1 of stage I;
      on day 2 of stage II, however, the recovery of WTh was again markedly improved
      compared with day 1. Blockade of adenosine receptors with 8-p-sulfophenyl
      theophylline failed to prevent the development of preconditioning against
      stunning. Northern blot analysis demonstrated an increase in heat stress protein
      (HSP) 70 mRNA 2 h after the preconditioning ischemia; at this same time point,
      immunohistochemical analysis revealed a concentration of HSP70 in the nucleus and
      an overall increase in staining for HSP70. 24 h after the preconditioning
      ischemia, Western dot blot analysis demonstrated an increase in HSP70. This study
      indicates the existence of a new, previously unrecognized cardioprotective
      phenomenon. The results demonstrate that a brief ischemic stress induces a
      powerful, long-lasting (at least 48 h) adaptive response that renders the
      myocardium relatively resistant to stunning 24 h later (late preconditioning
      against stunning). This adaptive response disappears within 10 d after the last
      ischemic stress but can be reinduced by another ischemic stress. Unlike early and
      late preconditioning against infarction, late preconditioning against stunning is
      not blocked by adenosine receptor antagonists, and therefore appears to involve a
      mechanism different from that of other forms of preconditioning currently known.
      The increase in myocardial HSP70 is compatible with, but does not prove, a role
      of HSPs in the pathogenesis of this phenomenon.

PMID- 7814640
TI  - Chronic metabolic acidosis decreases albumin synthesis and induces negative
      nitrogen balance in humans.
AB  - Chronic metabolic acidosis has been previously shown to stimulate protein
      degradation. To evaluate the effects of chronic metabolic acidosis on nitrogen
      balance and protein synthesis we measured albumin synthesis rates and urinary
      nitrogen excretion in eight male subjects on a constant metabolic diet before and
      during two different degrees of chronic metabolic acidosis (NH4Cl 2.1 mmol/kg
      body weight, low dose group, and 4.2 mmol/kg body weight, high dose group, orally
      for 7 d). Albumin synthesis rates were measured by intravenous injection of
      [2H5ring]phenylalanine (43 mg/kg body weight, 7.5 atom percent and 15 atom
      percent, respectively) after an overnight fast. In the low dose group, fractional
      synthesis rates of albumin decreased from 9.9 +/- 1.0% per day in the control
      period to 8.4 +/- 0.7 (n.s.) in the acidosis period, and from 8.3 +/- 1.3% per
      day to 6.3 +/- 1.1 (P < 0.001) in the high dose group. Urinary nitrogen excretion
      increased significantly in the acidosis period (sigma delta 634 mmol in the low
      dose group, 2,554 mmol in the high dose group). Plasma concentrations of insulin
      like growth factor-I, free thyroxine and tri-iodothyronine were significantly
      lower during acidosis. In conclusion, chronic metabolic acidosis causes negative
      nitrogen balance and decreases albumin synthesis in humans. The effect on albumin
      synthesis may be mediated, at least in part, by a suppression of insulin-like
      growth factor-I, free thyroxine and tri-iodothyronine.

PMID- 7814641
TI  - Localization of heparin-binding EGF-like growth factor in the smooth muscle cells
      and macrophages of human atherosclerotic plaques.
AB  - Heparin-binding EGF-like growth factor (HB-EGF) is a potent chemoattractant and
      mitogen for smooth muscle cells (SMC) in culture. To elucidate whether HB-EGF is
      implicated in the pathogenesis of human atherosclerosis, we examined
      immunohistochemical localization of HB-EGF in human aortic walls and
      atherosclerotic plaques. The medial SMC of the aorta in babies and children
      synthesized HB-EGF protein, while the number of SMC producing HB-EGF was
      dramatically decreased in young and middle-aged adults. In atherosclerotic
      plaques, however, marked production of HB-EGF protein was detected in SMC and
      macrophages of the plaques. Furthermore, EGF receptors, to which HB-EGF is known
      to bind, were detected in plaque SMC. These data suggest that HB-EGF may be
      implicated in the migration and proliferation of SMC that occurs in the normal
      development of arterial walls, and in the formation of atherosclerotic plaques.

PMID- 7814642
TI  - Adenosine triphosphate-dependent copper transport in isolated rat liver plasma
      membranes.
AB  - The process of hepatobiliary copper (Cu) secretion is still poorly understood: Cu
      secretion as a complex with glutathione and transport via a lysosomal pathway
      have been proposed. The recent cloning and sequencing of the gene for Wilson
      disease indicates that Cu transport in liver cells may be mediated by a Cu
      transporting P-type ATPase. Biochemical evidence for ATP-dependent Cu transport
      in mammalian systems, however, has not been reported so far. We have investigated
      Cu transport in rat liver plasma membrane vesicles enriched in canalicular or
      basolateral membranes in the presence and absence of ATP (4 mM) and an ATP
      regenerating system. The presence of ATP clearly stimulated uptake of
      radiolabeled Cu (64Cu, 10 microM) into canalicular plasma membrane vesicles and,
      to a lesser extent, also into basolateral plasma membrane vesicles. ATP-dependent
      Cu transport was dose-dependently inhibited by the P-type ATPase inhibitor
      vanadate, and showed saturation kinetics with an estimated Km of 8.6 microM and a
      Vmax of 6.9 nmol/min/mg protein. ATP-stimulated Cu uptake was similar in
      canalicular membrane vesicles of normal Wistar rats and those of mutant GY rats,
      expressing a congenital defect in the activity of the ATP-dependent canalicular
      glutathione-conjugate transporter (cMOAT). These studies demonstrate the presence
      of an ATP-dependent Cu transporting system in isolated plasma membrane fractions
      of rat liver distinct from cMOAT.

PMID- 7814643
TI  - Glucagon-like peptide-1 is a physiological incretin in rat.
AB  - Glucagon-like peptide-1 7-36 amide (GLP-1) has been postulated to be the primary
      hormonal mediator of the entero-insular axis but evidence has been indirect. The
      discovery of exendin (9-39), a GLP-1 receptor antagonist, allowed this to be
      further investigated. The IC50 for GLP-1 receptor binding, using RIN 5AH beta
      cell membranes, was found to be 0.36 nmol/l for GLP-1 and 3.44 nmol/l for exendin
      (9-39). There was no competition by exendin (9-39) at binding sites for glucagon
      or related peptides. In the anaesthetized fasted rat, insulin release after four
      doses of GLP-1 (0.1, 0.2, 0.3, and 0.4 nmol/kg) was tested by a 2-min intravenous
      infusion. Exendin (9-39) (1.5, 3.0, and 4.5 nmol/kg) was administered with GLP-1
      0.3 nmol/kg, or saline, and only the highest dose fully inhibited insulin
      release. Exendin (9-39) at 4.5 nmol/kg had no effect on glucose, arginine,
      vasoactive intestinal peptide or glucose-dependent insulinotropic peptide
      stimulated insulin secretion. Postprandial insulin release was studied in
      conditioned conscious rats after a standard meal. Exendin (9-39) (0.5 nmol/kg)
      considerably reduced postprandial insulin concentrations, for example by 48% at
      15 min (431 +/- 21 pmol/l saline, 224 +/- 32 pmol/l exendin, P < 0.001). Thus,
      GLP-1 appears to play a major role in the entero-insular axis.

PMID- 7814644
TI  - Overexpression of Glut4 protein in muscle increases basal and insulin-stimulated
      whole body glucose disposal in conscious mice.
AB  - The effect of increased Glut4 protein expression in muscle and fat on the whole
      body glucose metabolism has been evaluated by the euglycemic hyperinsulinemic
      clamp technique in conscious mice. Fed and fasting plasma glucose concentrations
      were 172 +/- 7 and 78 +/- 7 mg/dl, respectively, in transgenic mice, and were
      significantly lower than that of nontransgenic littermates (208 +/- 5 mg/dl in
      fed; 102 +/- 5 mg/dl in fasting state). Plasma lactate concentrations were higher
      in transgenic mice, (6.5 +/- 0.7 mM in the fed and 5.8 +/- 1.0 mM in fasting
      state) compared with that of non-transgenic littermates (4.7 +/- 0.3 mM in the
      fed and 4.2 +/- 0.5 mM in fasting state). In the fed state, the rate of whole
      body glucose disposal was 70% higher in transgenic mice in the basal state, 81
      and 54% higher during submaximal and maximal insulin stimulation. In the fasting
      state, insulin-stimulated whole body glucose disposal was also higher in the
      transgenic mice. Hepatic glucose production after an overnight fast was 24.8 +/-
      0.7 mg/kg per min in transgenic mice, and 25.4 +/- 2.7 mg/kg per min in
      nontransgenic mice. Our data demonstrate that overexpression of Glut4 protein in
      muscle increases basal as well as insulin-stimulated whole body glucose disposal.
      These results suggest that skeletal muscle glucose transport is rate-limiting for
      whole body glucose disposal and that the Glut4 protein is a potential target for
      pharmacological or genetic manipulation for treatment of patients with non
      insulin-dependent diabetes mellitus.

PMID- 7814645
TI  - Regulation of gene transcription of angiotensin II receptor subtypes in
      myocardial infarction.
AB  - Increasing evidence suggests that angiotensin II (AngII) acts as a modulator for
      ventricular remodeling after myocardial infarction. Using competitive reverse
      transcriptase polymerase chain reaction, nuclear runoff, and binding assays, we
      examined the regulation of AngII type 1a and 1b (AT1a-R and AT1b-R) and type 2
      receptor (AT2-R) expression in the infarcted rat heart as well as the effects of
      AngII receptor antagonists. AT1a-R mRNA levels were increased in the infarcted
      (4.2-fold) and noninfarcted portions (2.2-fold) of the myocardium 7 d after
      myocardial infarction as compared with those in sham-operated controls, whereas
      AT1b-R mRNA levels were unchanged. The amount of detectable AT2-R mRNA increased
      in infarcted (3.1-fold) and noninfarcted (1.9-fold) portions relative to that in
      the control. The transcription rates for AT1a-R and AT2-R genes, determined by
      means of a nuclear runoff assay, were significantly increased in the infarcted
      heart. The AngII receptor numbers were elevated (from 12 to 35 fmol/mg protein)
      in the infarcted myocardium in which the increases in AT1-R and AT2-R were 3.2-
      and 2.3-fold, respectively, while the receptor affinity was unchanged. Therapy
      with AT1-R antagonist for 7 d reduced the increase in AT1-R and AT2-R expressions
      in the infarcted heart together with a decrease in blood pressure, whereas
      therapy with an AT2-R antagonist did not affect mRNA levels and blood pressure.
      Neither AT1-R nor AT2-R antagonists affected the infarct sizes. These results
      demonstrated that myocardial infarction causes an increase in the gene
      transcription and protein expression of cardiac AT1a-R and AT2-R, whereas the
      AT1b-R gene is unaffected, and that therapy with an AT1-R antagonist, but not
      with an AT2-R antagonist, is effective in reducing the increased expression of
      AngII receptor subtypes induced by myocardial infarction.

PMID- 7814646
TI  - A distinct array of proinflammatory cytokines is expressed in human colon
      epithelial cells in response to bacterial invasion.
AB  - Pathogenic bacteria that penetrate the intestinal epithelial barrier stimulate an
      inflammatory response in the adjacent intestinal mucosa. The present studies
      asked whether colon epithelial cells can provide signals that are important for
      the initiation and amplification of an acute mucosal inflammatory response.
      Infection of monolayers of human colon epithelial cell lines (T84, HT29, Caco-2)
      with invasive strains of bacteria (Salmonella dublin, Shigella dysenteriae,
      Yersinia enterocolitica, Listeria monocytogenes, enteroinvasive Escherichia coli)
      resulted in the coordinate expression and upregulation of a specific array of
      four proinflammatory cytokines, IL-8, monocyte chemotactic protein-1, GM-CSF, and
      TNF alpha, as assessed by mRNA levels and cytokine secretion. Expression of the
      same cytokines was upregulated after TNF alpha or IL-1 stimulation of these
      cells. In contrast, cytokine gene expression was not altered after infection of
      colon epithelial cells with noninvasive bacteria or the noninvasive protozoan
      parasite, G. lamblia. Notably, none of the cell lines expressed mRNA for IL-2, IL
      4, IL-5, IL-6, IL-12p40, IFN-gamma, or significant levels of IL-1 or IL-10 in
      response to the identical stimuli. The coordinate expression of IL-8, MCP-1, GM
      CSF and TNF alpha appears to be a general property of human colon epithelial
      cells since an identical array of cytokines, as well as IL-6, also was expressed
      by freshly isolated human colon epithelial cells. Since the cytokines expressed
      in response to bacterial invasion or other proinflammatory agonists have a well
      documented role in chemotaxis and activation of inflammatory cells, colon
      epithelial cells appear to be programmed to provide a set of signals for the
      activation of the mucosal inflammatory response in the earliest phases after
      microbial invasion.

PMID- 7814647
TI  - Diminished expression of CD40 ligand by activated neonatal T cells.
AB  - CD40 and CD40 ligand (gp39) mediate contact-dependent T-B cell interaction. We
      determined the expression of CD40 ligand by activated neonatal T cells and the
      response of neonatal B cells when activated through CD40. Although expression of
      CD40 ligand peaked simultaneously in both activated adult and neonatal cells,
      neonatal T cells expressed significantly less CD40 ligand surface protein and
      mRNA than adult T cells. Activated thymocytes also expressed far less CD40 ligand
      than adult T cells. Consistent with these results, activated neonatal T cells
      exhibited less helper function than activated adult T cells. Neonatal T cells
      primed and restimulated in vitro expressed CD40 ligand in amounts comparable with
      adult T cells and provided B cell help more effectively. This suggests that the
      poor expression of CD40 ligand reflects antigenic naivete rather than an
      intrinsic defect of neonatal T cells. Neonatal B cells cultured with soluble CD40
      ligand (sgp39) and IL-10 produced IgM in amounts comparable with adult cells, but
      much less IgG and IgA. Nevertheless, neonatal B cells were capable of
      proliferation and class switching, since sgp39 and IL-4 induced proliferation and
      IgE production comparable to adult B cells and production of modest amounts of
      IgG. Together, these results indicate that diminished CD40 ligand expression,
      along with decreased production of lymphokines, may be responsible, at least in
      part, for the transient immunodeficiency observed in human neonates.

PMID- 7814648
TI  - Reproducing abnormal cholesterol biosynthesis as seen in the Smith-Lemli-Opitz
      syndrome by inhibiting the conversion of 7-dehydrocholesterol to cholesterol in
      rats.
AB  - The Smith-Lemli-Opitz syndrome is a recessive inherited disorder characterized by
      neurologic developmental defects and dysmorphic features in many organs.
      Recently, abnormal cholesterol biosynthesis with impaired conversion of 7
      dehydrocholesterol to cholesterol has been discovered in homozygotes. To
      reproduce the biochemical abnormality, BM 15.766, a competitive inhibitor of 7
      dehydrocholesterol-delta 7-reductase, the enzyme that catalyzes the conversion of
      7-dehydrocholesterol into cholesterol was fed by gavage to rats. After 14 d,
      plasma cholesterol concentrations declined from 48 mg/dl to 16 mg/dl and 7
      dehydro-cholesterol levels rose from trace to 17 mg/dl. Hepatocytes surrounding
      the central vein developed balloon necrosis. Stimulating cholesterol synthesis
      with cholestyramine followed by BM 15.766 produced an additional 40% decline (P <
      0.05) in plasma cholesterol and 34% increase in 7-dehydrocholesterol levels
      compared to the inhibitor alone. Adding 2% cholesterol to the diet during the
      second week of BM 15.766 treatment increased plasma cholesterol threefold and
      decreased 7-dehydrocholesterol concentrations 55%. Hepatic 3-hydroxy-3
      methylglutaryl co-enzyme A (HMG-CoA) reductase activity increased 73% with a 3.9
      fold rise in mRNA levels but cholesterol 7 alpha-hydroxylase activity decreased
      slightly though mRNA levels increased 1.4 times with BM 15.766 treatment. These
      results demonstrate that BM 15.766 is a potent inhibitor of 7-dehydrocholesterol
      delta 7-reductase. The model reproduces abnormal cholesterol biosynthesis as seen
      in the Smith-Lemli-Opitz syndrome and is useful to test different treatment
      strategies. Stimulating early steps of cholesterol synthesis worsens the
      biochemical abnormalities while feeding cholesterol inhibits abnormal synthesis,
      improves the biochemical abnormalities and prevents liver damage.

PMID- 7814649
TI  - Novel production of interleukin-1 receptor antagonist peptides in normal human
      cornea.
AB  - Interleukin-1 receptor antagonist (IL-1ra) is an important modulator of IL-1
      activity in a variety of tissues. IL-1ra is differentially produced by different
      cell types as a 22-26-kD secreted peptide (sIL-1ra) and/or a smaller 16- or 18-kD
      intracellular peptide (icIL-1ra). This study was undertaken to evaluate the
      production of IL-1ra in the human cornea. IL-1ra mRNA can be detected in early
      passage human corneal epithelial cells and corneal stromal fibroblasts and is
      significantly enhanced by IL-1. Corneal endothelial cells do not express IL-1ra
      mRNA. Immunohistochemical studies of cultured corneal cells and whole human
      cornea demonstrate IL-1ra protein production by both the epithelial and stromal
      cells but not the endothelial cells. Reverse transcriptase polymerase chain
      reaction, ELISA, and immunoprecipitation studies indicate that corneal epithelial
      cells are capable of producing both icIL-1ra and sIL-1ra forms of IL-1ra whereas
      the corneal stromal cells produce only icIL-1ra. In addition to the larger 18-kD
      icIL-1ra, both corneal epithelial and stromal cells are also capable of producing
      a smaller recently described 16-kD icIL-1ra. Thus, the differential production of
      IL-1ra in the human cornea is unique; whereas both epithelial and stromal cells
      produce icIL-1ra (type 1 and type 2), the epithelial cells appear to also produce
      sIL-1ra. It is proposed that these IL-1ra proteins may play an important role in
      regulating IL-1-induced corneal inflammation.

PMID- 7814651
TI  - Contribution of transcranial color-coded real-time sonography to the
      etiopathogenetic classification of middle cerebral artery stenosis.
AB  - Transcranial color-coded real-time sonography (TCCS) and cranial computed
      tomography were applied to patients with middle cerebral artery (MCA) stenosis to
      evaluate whether these techniques may disclose additional aspects of the
      pathophysiology of the stenotic lesion. In 15 patients with MCA stenosis
      identified by transcranial Doppler sonography, the echogenicity of the stenotic
      segment was estimated subjectively by TCCS. The density of the stenotic segment,
      prior to being detected by TCCS, was quantified by computed tomography. In 5 of
      the 15 patients, transcranial image-directed Doppler sonography identified a
      hyperechogenic lesion in association with the stenotic vascular segment; computed
      tomography demonstrated a "dense" artery (Hounsfield units [HU] > 120) in the
      corresponding vascular segment. In 10 patients the echogenicity of the stenotic
      segment was found to be normal, with a computed tomography density of < 100 HU in
      the corresponding segment. Hyperechogenic and hyperdense stenotic vascular
      segments in TCCS and computed tomography, respectively, may indicate an
      arteriosclerotic vascular lesion with calcium deposits. Normal echogenicity and
      normal to slightly elevated computed tomography-density of a stenotic vascular
      segment may suggest the presence of a thrombotic/embolic lesion.

PMID- 7814652
TI  - Use of vaginosonographic measurements of endometrial thickness in the
      identification of abnormal endometrium in peri- and postmenopausal bleeding.
AB  - One hundred and seventy seven women with peri- and postmenopausal bleeding were
      subjected to vaginosonographic examination followed by thorough pathological
      examination of the uterine curetting samples. A mean endometrial thickness
      (double layer) of 13.2 +/- 3.6 mm and 8.2 +/- 4.8 mm were found in those with and
      without histological abnormalities, respectively. Endometrial thickness of less
      than 7 mm, however, was found to be predictive of normal endometrium (100%
      sensitivity, 46% specificity) and can, therefore, be used to separate those who
      require diagnostic curettage from those who do not. These findings suggest that
      this relatively simple, noninvasive procedure can be used as a screening test for
      patients with peri- or postmenopausal bleeding.

PMID- 7814650
TI  - Interleukin-8 gene induction in the myocardium after ischemia and reperfusion in
      vivo.
AB  - Neutrophil adhesion and direct cytotoxicity for cardiac myocytes require
      chemotactic stimulation and are dependent upon CD18-ICAM-1 binding. To
      characterize the potential role of IL-8 in this interaction, canine IL-8 cDNA was
      cloned and the mature recombinant protein expressed in Escherichia coli BL21
      cells. Recombinant canine IL-8 markedly increased adhesion of neutrophils to
      isolated canine cardiac myocytes. This adhesion resulted in direct cytotoxicity
      for cardiac myocytes. Both processes were specifically blocked by antibodies
      directed against CD18 and IL-8. In vivo, after 1 h of coronary occlusion, IL-8
      mRNA was markedly and consistently induced in reperfused segments of myocardium.
      IL-8 mRNA was not induced in control (normally perfused) myocardial segments.
      Minimal amounts of IL-8 mRNA were detected after 3 or 4 h of ischemia without
      reperfusion. Highest levels of induction were evident in the most ischemic
      myocardial segments. IL-8 mRNA peaked in the first 3 h of reperfusion and
      persisted at high levels beyond 24 h. IL-8 staining was present in the
      inflammatory infiltrate near the border between necrotic and viable myocardium,
      as well as in small veins in the same area. These findings provide the first
      direct evidence for regulation of IL-8 in ischemic and reperfused canine
      myocardium and support the hypothesis that IL-8 participates in neutrophil
      mediated myocardial injury.

PMID- 7814653
TI  - Sonographic detection of clinically unsuspected swallowed toothpicks and their
      gastrointestinal complications.
AB  - We retrospectively analyzed the clinical presentation and imaging investigation
      in 4 cases of surgically (2 cases) or endoscopically (2 cases) proven toothpick
      related gastrointestinal perforation. The toothpick perforated the stomach (2
      cases), the sigmoid (1 case), and the ileum (1 case). Sonographic appearance of
      the toothpick was a linear, hyperechoic (3 cases) or hypoechoic (1 case) image of
      variable length (mean: 2.5 cm) with inconsistent posterior shadowing in the
      longitudinal axis. In transverse section a hyperechoic dot (4 cases) with clear,
      thin, sharp, posterior shadowing (3 cases) was seen. Following sonography (4
      cases), CT scan (2 cases), and upper GI study (2 cases), the preoperative
      diagnosis of GI perforation by foreign body compatible with toothpick was made in
      all cases, although none of the patients was aware of having swallowed a
      toothpick. This information will be of help in making early sonographic diagnosis
      of toothpick-related GI perforation in patients with or without symptoms.

PMID- 7814654
TI  - Color Doppler ultrasonography and serum CA 125 in the differentiation of benign
      and malignant ovarian tumors.
AB  - Color Doppler ultrasonography and serum CA 125 were used to evaluate 114 adnexal
      tumors prior to surgery. Six patients were excluded from this study because of
      ovarian cancer, borderline ovarian malignancy, and tubal gestation. A total of
      108 patients were eligible: 83 patients with benign and 25 patients with
      malignant ovarian tumors. Resistance index (RI) was used to determine the
      peripheral resistance of intratumoral vessels. The cutoff point for the RI was
      defined as 0.5. The blood flow was considered to be normal when the RI was
      greater than 0.5 and abnormal when it was less than 0.5. The blood flow was
      detected in 100% of malignant tumors and 59% of benign tumors. The initial cutoff
      value for CA 125 was 35 U/mL. Sensitivity, specificity, positive predictive
      value, and negative predictive value were compared in terms of RI, serum CA 125,
      and a combination of the two. Our conclusion is that the combination of RI and CA
      125 gives a sensitivity of 100% and negative predictive value of 100%. If the
      cutoff point of CA 125 was raised from 35 to 65 U/mL, then a specificity of 100%
      and positive predictive value of 100% were also attained with the use of RI and
      CA 125 without changes in sensitivity or negative predictive value. We conclude
      that the combination of color Doppler ultrasonography and serum CA 125 is an
      effective method to differentiate benign from malignant ovarian tumors.

PMID- 7814655
TI  - Use of the transverse cerebellar diameter/abdominal circumference ratio in
      pregnancies at risk for intrauterine growth retardation.
AB  - A prospective study was conducted to evaluate the ability of the transverse
      cerebellar diameter/abdominal circumference ratio to identify growth-retarded
      fetuses. Of the cases analyzed, 48 of 87 (55%) were growth retarded by birth
      weight. The transverse cerebellar diameter/abdominal circumference ratio
      identified growth retardation with a sensitivity of 71%, specificity of 77%,
      positive predictive value of 79%, and negative predictive value of 68%. Fourteen
      growth-retarded fetuses were missed by the ratio; however, 57% of the missed
      cases were severely growth retarded. The transverse cerebellar diameter/abdominal
      circumference ratio can be useful for the assessment of fetal growth retardation;
      however, the ratio may be normal in cases of severe fetal growth retardation.

PMID- 7814656
TI  - Richter's hernia strangulated in a spigelian hernia: ultrasonic diagnosis.

PMID- 7814657
TI  - Gas in the gallbladder due to duodeno-cholecystic fistula: a rare complication of
      a penetrating duodenal ulcer. Sonographic findings with CT correlation.

PMID- 7814658
TI  - Prenatal sonographic findings of Apert syndrome.

PMID- 7814659
TI  - Congenital cystic adenomatoid malformation of the lung with prolonged marked lung
      compression and neonatal survival.

PMID- 7814660
TI  - A large yolk sac: a possible clue to early diagnosis of partial hydatidiform
      mole.

PMID- 7814661
TI  - Differential development of alpha-bungarotoxin-sensitive and alpha-bungarotoxin
      insensitive nicotinic acetylcholine receptors in the chick retina.
AB  - The development of cells containing neuronal nicotinic receptors (nAChRs) in the
      chick retina was investigated by means of immunohistochemical techniques with
      antibodies directed against the alpha 3 and alpha 8 nAChR subunits. The alpha 3
      subunit is one of the major alpha-bungarotoxin-insensitive nicotinic receptor
      subunits in the chick retina, whereas alpha 8 appears to be the most common alpha
      bungarotoxin-sensitive subunit in the same structure, alpha 3-like
      immunoreactivity (alpha 3-LI) was first detected in cells of the vitreal margin,
      on the embryonic day 4.5 (E4.5). alpha 8-LI was first detected in the same type
      of cell almost a day later. However, the processes of alpha 8-LI cells developed
      much faster than those of alpha 3-LI cells, generating visible stained laminae in
      the prospective inner plexiform layer as early as E7. alpha 3-LI was only clearly
      seen in laminae of the inner plexiform layer by E12. By this date, both alpha 3
      and alpha 8-LI were seen in the same types of cells as in the adult retina, i.e.,
      amacrines, displaced ganglion cells, and cells of the ganglion cell layer for
      alpha 3-LI; and amacrines, bipolar cells, and cells of the ganglion cell layer
      for alpha 8-LI. These results reveal different patterns of development of cells
      containing the alpha 3 and alpha 8 nAChR subunits in the chick retina and
      indicate that those nAChR subunits are expressed in the chick retina before
      choline acetyltransferase-positive cells can be detected and well before
      synaptogenesis. These data also suggest that nAChRs may have a developmental
      function in the retina.

PMID- 7814662
TI  - Morphological relationships of choleragenoid horseradish peroxidase-labeled
      spinal primary afferents with myenteric ganglia and mucosal associated lymphoid
      tissue in the cat esophagogastric junction.
AB  - The goal of the present study was to gain insight into the environmental factors
      influencing the activity of primary spinal afferent fibers in the different
      layers of the esophagogastric junction of the cat and, thus, to analyze the
      relationships of these afferents with various cellular components. Spinal primary
      afferent fibers were selectively labeled by anterogradely transported
      choleragenoid horseradish peroxidase conjugate (B-HRP). B-HRP was injected into
      the thoracic dorsal root ganglion at the T8-T13 levels. 6-Hydroxydopamine-induced
      sympathectomy was performed prior to B-HRP injection in order to prevent
      otherwise unavoidable labeling of sympathetic fibers in the gut wall. Numerous
      labeled fibers ran between, around, and within the myenteric ganglia. Others
      crossed the muscle layers directly and entered the mucosa, where some ran near
      granulocytes and around or through solitary lymphoid follicles. Labeled fibers
      were observed in the squamous esophageal epithelium but not in the fundic
      glandular epithelium. The fibers in the myenteric area are probably connected to
      the muscular tension receptors that have been detected by electrophysiologic
      techniques. This assumption is based on the observation that only a few fibers
      appear to terminate in muscle layers and on the fact that the myenteric area is
      very narrow and subject to powerful forces. Fibers in the myenteric ganglia could
      be involved in local efferent functions. Fibers in the mucosa could act as
      nociceptors and might be involved in local immunological responses.

PMID- 7814663
TI  - Expression of the neural cell adhesion molecule (NCAM) and polysialic acid during
      taste bud degeneration and regeneration.
AB  - Taste receptor cells are replaced throughout life, accompanied by continuing
      synaptogenesis between newly formed taste cells and first-order gustatory fibers.
      The neural cell adhesion molecule (NCAM) is expressed by a subset of taste cells
      in adult rodents and appears on gustatory nerve fibers during development prior
      to differentiation of the taste buds. We employed antibodies against the
      extracellular domain of the NCAM polypeptide (mAb 3F4) and against polysialic
      acid (PSA) residues found on embryonic forms of NCAM (mAb 5A5) to investigate the
      relationship between the expression of these molecules and the innervation of
      taste buds in adult rats. In unoperated rats, anti-NCAM recognized a subset of
      cells within the vallate taste buds and also the fibers of the glossopharyngeal
      (IXth) nerve, including those innervating the gustatory epithelium. Taste bud
      cells did not express PSA but mAb 5A5 immunoreactivity was observed on some
      fibers of the IXth nerve, including a few that entered the taste buds. Bilateral
      crush of the IXth nerve resulted in the loss of NCAM expression from the
      gustatory epithelium within 8 days. As IXth nerve fibers reinnervated the
      epithelium, NCAM expression was seen first in the nerve, followed by increased
      expression in the epithelium as the taste cells differentiated from their
      precursors. PSA expression by fibers of the IXth nerve did not return to normal
      until well after the regeneration of the vallate taste buds. The present results
      demonstrate that taste cell expression of NCAM is dependent upon innervation by
      the IXth nerve and that NCAM expression appears in the nerve prior to its
      expression in the differentiating epithelium during regeneration.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7814664
TI  - Tangential organization of callosal connectivity in the cat's visual cortex.
AB  - Cells and/or terminals of corticocortical pathways in mammalian visual cortex
      often have a discontinuous distribution across the surface of the cortex. A
      modular organization of cortical function has been shown to underlie the
      tangential segregation of many inputs and outputs. Here, we present evidence that
      the callosal pathway in the visual cortex of the cat follows these general
      principles. Large injections of wheat germ agglutinin-horseradish peroxidase or
      biotinylated dextran amine were made in areas 17 and 18, and callosal labeling
      was analyzed in tangential sections. The band of callosal cells and terminals
      straddling the border of areas 17 and 18 was not uniform but varied in density in
      a complicated fashion. Fluctuations in density of callosal connections became
      more clear 2-3 mm lateral or medial to the 17/18 border, as the callosal labeling
      became less dense. Here, regular fluctuations with a periodicity of about 1 mm in
      area 17, and slightly greater than 1 mm in area 18 were apparent. Cytochrome
      oxidase staining in areas 17 and 18 showed a pattern of dense blobs with the same
      spacing as the callosal labeling in these areas, and the blobs were found to
      align with the patches of callosal labeling. Larger, more irregularly spaced
      stripes of callosal labeling extended from the lateral part of area 18 across
      area 19 and into more lateral visual areas. These results suggest that the
      callosal pathway in the cat's visual cortex has a patchy distribution similar to
      many ipsilateral corticocortical projections, and that the columnar system marked
      by cytochrome oxidase is important for the organization of (interhemispheric)
      corticocortical connectivity in cats.

PMID- 7814665
TI  - Lack of Purkinje cell loss in adult rat cerebellum following protracted axotomy:
      degenerative changes and regenerative attempts of the severed axons.
AB  - The cerebellar Purkinje cells, due to their geometrical disposition and their
      high calbindin content, offer an optimal system in which to test the adequacy of
      current opinions on axotomy effects. We have, therefore, analyzed with calbindin
      immunostaining the morphological changes of Purkinje cells from 1 day to 6 months
      after axonal section in the cerebellar white matter. This method allows us to
      study the morphological changes in their dendrites, cell bodies, and axons. We
      have also searched for simultaneous changes in glial cells and vascularization by
      using cell type-specific markers. In addition, an ultrastructural study of
      Purkinje cells, 7 days after large electrolytic lesions affecting the white
      matter and the overlying granular layer, was carried out to determine whether
      amputation of the recurrent collateral system provokes a fast neuronal death.
      Neither the Purkinje cells axotomized close to their cell bodies (electrolytic
      lesions) nor those axotomized in the white matter (cerebellar transection)
      degenerated. Thus, this study demonstrates that Purkinje cells are extremely
      resistant to axotomy; those severed in the white matter at distances varying from
      100 microns to 3 mm remain alive for as long as 6 months. At all survival times
      studied, axotomized Purkinje cells exhibited few changes in their somata and
      dendrites, as well as in their glial microenvironment. The major changes occurred
      in the axonal compartment. Axonal alterations, namely the presence of torpedoes
      and hypertrophy of the recurrent collateral system, were early events already
      noticeable 24 hours after the lesion, although they later differed in their time
      course and spatial distribution. It is remarkable that the distal segments of the
      central stumps of the cut axons survived in large numbers without any apparent
      retraction, with their terminal varicosities apposed to the wall of the wound
      cavity even 6 months after the lesion. Nevertheless, these segments were thinner
      than normal Purkinje cell axons (axonal atrophy). Despite this apparent
      immutability, some regenerative attempts did occur in the severed axons, such as
      axonal sprouts penetrating the deeper region of the granular layer in zones close
      to the lesion, presence of arciform axons, and hypertrophy of the recurrent
      collateral system. However, the Purkinje cell axons did not regenerate, and these
      neurons remained separated from their targets by a cavity in virtually all cases.

PMID- 7814666
TI  - Contribution of neurons born during embryonic, juvenile, and adult life to the
      brain of adult canaries: regional specificity and delayed birth of neurons in the
      song-control nuclei.
AB  - Neurogenesis occurs in adult song birds, which suggests that neurons born after
      hatching may contribute to histogenesis and plasticity of the avian brain.
      However, little is known about the overall contribution to the mature brain of
      neurons born in juveniles and adults, and how this process affects different
      regions of the avian brain. In fact, studies of the histogenesis of the avian
      forebrain have made the classical assumption that neuronal birth ends before
      hatching. Here we determined the contribution of neurons born before and after
      hatching to different regions throughout the adult canary brain. Male canaries
      were injected with [3H]-thymidine at different times during embryonic, juvenile,
      and adult life. The position of labeled neurons was mapped in parasagittal brain
      sections. Because all birds were killed as adults, results indicate the time of
      birth of neurons that survived to adulthood in different structures of the avian
      brain. Injection at embryonic day (E) 5 or E9 resulted in labeled neurons in all
      regions of the neuroaxis. The vast majority of neurons outside of the
      telencephalon were born before E9. One exception was a discrete region in the
      dorsal thalamus, a part of the song-control circuit, where neurons continued to
      be born after E9. Most regions of the telencephalon had a high proportion of its
      neurons labeled by the embryonic injections. In particular, archistriatum,
      anterior neostriatum, and the hippocampus had most of their neurons labeled
      before hatching. This indicates that many of the telencephalic neurons born in
      the embryo are long lived and are not replaced by other neurons that continue to
      be added to the telencephalon after hatching. Neurons labeled by [3H]-thymidine
      injections after hatching were restricted to the telencephalon and contributed
      importantly to many regions. In particular, the avian striatum (lobus
      parolfactorius, LPO) received a large number of its neurons during the first 20
      days of life, but continued to incorporate new neurons throughout juvenile and
      adult life. Neurons continued to be added to the telencephalon of adults (even in
      4-year-old birds). The distribution of labeled neurons after [3H]-thymidine
      injections in adults was similar to that observed in latter stages of juvenile
      development. The contribution of neurons born at different ages from embryonic
      development to adulthood varied among different anatomical subdivisions of the
      canary brain. this could, in part, explain differences in the cytoarchitecture
      and plasticity between brain regions. Neurogenesis after hatching may allow the
      modification of selected brain circuits as the bird matures and ages.

PMID- 7814667
TI  - Immunohistochemical localization of substance P receptor in the central nervous
      system of the adult rat.
AB  - In an attempt to reveal the function sites of substance P (SP) in the central
      nervous system (CNS), the distribution of SP receptor (SPR) was
      immunocytochemically investigated in adult rat and compared with that of SP
      positive fibers. SPR-like immunoreactivity (LI) was mostly localized to neuronal
      cell bodies and dendrites. Neurons with intense SPR-LI were distributed densely
      in the cortical amygdaloid nucleus, hilus of the dentate gyrus, locus ceruleus,
      rostral half of the ambiguus nucleus, and intermediolateral nucleus of the
      thoracic cord; moderately in the caudatoputamen, nucleus accumbens, olfactory
      tubercle, median, pontine, and magnus raphe nuclei, laminae I and III of the
      caudal subnucleus of the spinal trigeminal nucleus, and lamina I of the spinal
      cord; and sparsely in the cerebral cortex, basal nucleus of Meynert, claustrum,
      gigantocellular reticular nucleus, and lobules IX and X of the cerebellar vermis.
      Neurons with weak to moderate SPR-LI were distributed more widely throughout the
      CNS. The regional patterns of distribution of SPR-LI were not necessarily the
      same as those of SP-positive fibers. The entopedunucular nucleus, substantia
      nigra, and lateral part of the interpeduncular nucleus showed intense SP-LI but
      displayed almost no SPR-LI. Conversely, the hilus of the dentate gyrus,
      anterodorsal thalamic nucleus, central nucleus of the inferior colliculus, and
      dorsal tegmental nucleus showed intense to moderate SPR-LI but contained few
      axons with SP-LI. These findings confirmed the presence of the "mismatch" problem
      between SP and SPR localizations. However, the distribution of SPR-LI was quite
      consistent with that of the SP-binding activity, which has been studied via
      autoradiography. This indicates that the sites of SPR-LI revealed in the present
      study represent most, if not all, sites of SP-binding activity.

PMID- 7814668
TI  - Ultrastructural and immunocytochemical characterization of primary afferent
      terminals in the rat cuneate nucleus.
AB  - The cuneate nucleus is a relay center for somatosensory information by receiving
      tactile and proprioceptive inputs from primary afferent fibers that ascend in the
      dorsal funiculus. The morphology, synaptic contacts, and neurochemical content of
      primary afferent terminals in the cuneate nucleus of rats were investigated by
      combining anterograde transport of horseradish peroxidase conjugated to wheat
      germ agglutinin or to cholera toxin (injected in cervical dorsal root ganglia)
      with postembedding immunogold labeling for glutamate and GABA. Both tracers gave
      similar results. Two types of terminals were labeled: type I terminals were
      irregularly shaped, had a mean area of 4.0 microns 2, synapsed on several
      dendrites, and were contacted by other terminals, some of which were GABA
      positive. Type II terminals were dome-shaped, had a mean area of 2.18 microns 2,
      and made synaptic contact on a single dendrite. All the anterogradely labeled
      terminals (interpreted as endings of primary afferents) were enriched in
      glutamate but not in GABA. The finding that identified primary afferent terminals
      are enriched in glutamate with respect to other tissue profiles strongly suggests
      a neurotransmitter role for glutamate in this afferent pathway to the rat cuneate
      nucleus.

PMID- 7814669
TI  - Cloning and in situ hybridization analysis of estrogen receptor, progesterone
      receptor, and androgen receptor expression in the brain of whiptail lizards
      (Cnemidophorus uniparens and C. inornatus).
AB  - Gonadal steroid hormones act upon specific areas of the vertebrate brain to
      affect the reproductive physiology and behavior of the animal. Steroid receptors
      are members of a superfamily of ligand-dependent transcription factors that
      mediate the effects of steroid hormones by modulating gene expression in the
      cells containing the receptors. The neuroanatomical distributions of steroid
      receptor-containing cells have been described for several species by using
      steroid autoradiography, immunocytochemistry, and more recently in situ
      hybridization. We have used the polymerase chain reaction to amplify and clone
      fragments of the estrogen receptor, progesterone receptor, and androgen receptor
      of whiptail lizards (genus Cnemidophorus). These clones were used to produce
      probes for use in in situ hybridization assays and to map the neuroanatomical
      distribution of all three sex steroid hormone receptors in the forebrains of
      unisexual (C. uniparens) and sexual (C. inornatus) species of whiptail lizards.
      The distribution of receptor-expressing cells reported here is in general
      agreement with previous reports in other species with receptor-containing cells
      concentrated in septal, amygdaloid, cortical, preoptic, and hypothalamic nuclei.

PMID- 7814670
TI  - Extrasynaptic localization of taurine-like immunoreactivity in the lamprey spinal
      cord.
AB  - Taurine is an endogenous amino acid that can occur in nerve terminals in the
      central nervous system and that can produce inhibitory neuronal responses. It is
      unclear, however, whether this amino acid can function as a synaptic transmitter.
      To examine the distribution of taurine at high anatomical resolution in a
      vertebrate, light and electron microscopic immunocytochemical postembedding
      techniques were applied to the lamprey spinal cord (Ichtyomyzon unicuspis and
      Lampetra fluviatilis), which contains many large, unmyelinated axons. The most
      intense immunolabeling occurred in a population of liquor-contacting cells
      (tanycytes), located around the central canal, which extended processes to the
      dorsal, lateral, and ventral margins of the spinal cord. In addition, a
      proportion of the taurine-immunoreactive cells contained gamma-aminobutyric acid
      (GABA)-like immunoreactivity. A moderate level of taurine immunoreactivity was
      also present in ependymal cells, located around the central canal, as well as in
      astrocytes throughout all regions of the spinal cord. At the ultrastructural
      level, the taurine immunoreactivity showed an even distribution in the cytoplasm
      of the labeled cells. In contrast to the glial labeling, neuronal cell bodies and
      axons exhibited very low levels of taurine labeling, which were similar to the
      level of background labeling. The synaptic vesicle clusters within the axons did
      not show any clear accumulation of taurine immunoreactivity. These results
      suggest that taurine may have metabolic roles in the lamprey spinal cord, and, as
      in other systems, it may take part in osmoregulation. However, the lack of
      immunolabeling in presynaptic elements is not consistent with a role of taurine
      as a synaptic transmitter.

PMID- 7814671
TI  - Serotonin-immunoreactive neurons and endogenous serotonin in the opisthosomal
      ventral nerve cord of the horseshoe crab, Limulus polyphemus.
AB  - It has been suggested that serotonin serves as a neurotransmitter in the
      horseshoe crab, Limulus polyphemus. While some studies of identified groups of
      central neurons have been conducted, little is known concerning the neuronal
      organization in Limulus central ganglia. This study was undertaken to determine
      the localization of serotoninergic neurons in the opisthosomal ventral nerve cord
      of Limulus and to construct a basis for further comparative biochemical and
      pharmacological studies of the specific function of these neurons. Endogenous
      serotonin was detected in the ventral nerve cord (chain of abdominal ganglia) by
      high-performance liquid chromatography and electrochemical detection (HPLC-EC).
      Endogenous serotonin was quantified in the 9th through 13th ganglia, anterior
      (hemal) nerves, posterior (branchial) nerves, and connectives. The serotonin
      content in the abdominal ganglia was significantly reduced when the ganglia were
      incubated for 24 hours in Leibovitz's (L-15) medium containing reserpine or 5,7
      dihydroxytryptamine (5,7-DHT), neurotoxins that block the uptake of serotonin
      into storage vesicles. The distribution of serotonin-immunoreactive neurons in
      the ventral nerve cord was determined by indirect immunocytochemistry. Treatment
      of the chain of ganglia with an anti-serotonin antiserum followed by treatment
      with a fluorescent-labeled antiserum raised against the primary antibody
      demonstrated specific staining in each ganglion, the ganglionic roots, and
      connectives. Clusters of serotonin-immunoreactive neurons were observed
      anteriolaterally and posteriorly in each ganglion. Processes from dense fiber
      bundles extended from these clusters of neurons to the central region of each
      ganglion. These results demonstrate that serotonin-immunoreactive neurons are
      present in the opisthosomal ventral nerve cord of the horseshoe crab and that
      serotonin may function as a neurotransmitter.

PMID- 7814672
TI  - Spinal cord lamina V and lamina VII interneuronal projections to sympathetic
      preganglionic neurons.
AB  - This light and electron microscopic study sought to localize spinal cord
      interneurons that contribute to the normal and abnormal physiological regulation
      of spinal sympathetic preganglionic function. Sympathetic preganglionic neurons
      in caudal C8 through T4 of rat spinal cord were retrogradely labeled with wheat
      germ agglutinin (WGA) and/or cholera beta subunit (CT beta) following injections
      into the superior cervical ganglion (SCG). With two exceptions, the observed
      locations of retrogradely WGA- and CT beta-labeled sympathetic preganglionic
      neurons were as expected from previous studies. The exceptions were restricted
      populations of cells in caudal C8 and rostral T1 spinal segments. These neurons
      were classified as ventrolateral (vlSPN) and ventromedial (vmSPN) sympathetic
      preganglionic neurons; their somata and dendrites encircled dorsolateral lamina
      IX motoneurons. Only WGA was transported transneuronally following the retrograde
      labeling of sympathetic preganglionic neurons. Transneuronally WGA-labeled spinal
      interneurons were located principally in the reticulated division of lamina V and
      dorsolateral lamina VII. A strict segmental organization was observed. All
      transneuronally labeled interneurons were ipsilateral to, and coextensive with,
      retrogradely WGA-labeled sympathetic preganglionic neurons. Electron microscopic
      observations suggested that retrograde transsynaptic passage of WGA occurred
      within the sympathetic preganglionic neuropil and showed further that similar
      classes of organelles were WGA immunoreactive in retrogradely labeled sympathetic
      preganglionic neurons and in transneuronally labeled lamina V and lamina VII
      neurons: 1) cisternae and vesicles at the trans face of the Golgi apparatus, 2)
      large endosomes/dense bodies, and 3) multivesicular bodies. The data are
      consistent with two hypotheses: 1) Somatic and visceral primary afferent inputs
      to thoracic spinal cord modify segmental sympathetic preganglionic function
      through activation of a disynaptic pathway involving lamina V and/or lamina VII
      interneurons, and 2) long-loop propriospinal pathways access sympathetic
      preganglionic neurons through symmetrical, segmental interneuronal circuitry.

PMID- 7814673
TI  - Structure and function of gustatory neurons in the nucleus of the solitary tract.
      I. A classification of neurons based on morphological features.
AB  - Prior investigations in other laboratories have provided convincing evidence that
      the neurons of the rostral nucleus of the solitary tract (rNST) can be grouped
      according to their physiological response properties or morphologic features. The
      present study is based on the premise that the response properties of gustatory
      neurons are related to, and perhaps governed by, their morphology and
      connectivity. In this first phase of our ongoing investigation of structure
      function relationships in the rNST of the rat, we have used intracellular
      injection of neurobiotin to label individual physiologically characterized
      gustatory neurons. A total of 63 taste-sensitive neurons were successfully
      labeled and subjected to three-dimensional quantitative and qualitative analysis.
      A cluster analysis using six morphologic features (total cell volume, soma area,
      mean segment length, swelling density, spine density, and number of primary
      dendrites) was used to identify six cell groups. Subsequent analyses of variance
      and posthoc comparisons verified that each of these six groups differed from all
      others with respect to at least one variable, so each group was "typified" by at
      least one of the six morphologic features. Neurons in group A were found to be
      the smallest neurons in the sample. The cells in group B had small somata and
      exhibited the highest swelling density of any group. Group C neurons were
      distinguished by dendrites with long, spine-free branches. These dendrites were
      significantly longer than those of any other group except Group F. The neurons in
      group D had more primary dendrites than any other group. Group E neurons
      possessed dendrities with the lowest swelling density but the most spines of any
      group. The cells in group F were the largest neurons in our sample and possessed
      the largest somata of any group. Thus overall cell size and density of dendritic
      spines and swellings were found to be particularly important variables in this
      classification scheme. Our preliminary results suggest that the number and
      density of dendritic spines (as well as other morphologic features) may be
      related to a given neuron's most effective stimulus, indicating that it will
      indeed be possible to use the criteria established in the present investigation
      to derive structure-function relationships for gustatory neurons in the rNST.

PMID- 7814674
TI  - Effects of denervation upon receptor cell survival and basal cell proliferation
      in tuberous electroreceptor organs of a weakly electric fish.
AB  - Weakly electric fish generate electric fields for the purposes of electrolocation
      and communication. These fields are detected by specialized receptor organs: the
      tuberous organs. In the present study we investigated the effects of denervation
      upon receptor cell survival and progenitor (basal) cell proliferation rate. The
      left, infraorbital, anterior lateral line nerve of brown ghosts (Apteronotus
      leptorhynchus) was sectioned, and the proximal stump was dipped in ricin to
      prevent regrowth. In groups of four, the animals were given two daily injections
      of the cell proliferation marker bromodeoxyuridine (BrdU) for 2 days at 1, 2, 3,
      or 4 weeks following denervation. At the completion of the BrdU injection
      schedule, a piece of cheek skin, rostroventral to the eye, was removed from the
      left (denervated) and the right (intact) sides and processed for light microscopy
      or immunocytochemistry. Our results show: (1) there is progressive receptor cell
      death and tuberous organ degeneration following denervation; (2) basal cell
      proliferation increases steadily with time after denervation and tuberous organ
      degeneration; and (3) despite denervation, some proliferating basal cells
      differentiate into receptor cells, but these new receptor cells eventually die.
      These results suggest that innervation is essential for tuberous electroreceptor
      cell survival and that the rate at which basal cells proliferate is regulated by
      receptor cell health, locally released factors, or both.

PMID- 7814675
TI  - Comparative anatomy of serotonin-like immunoreactive neurons in isopods: putative
      homologues in several species.
AB  - It is now commonly accepted that the arthropod nervous system has evolved only
      once, and so homologies between crustacean and insect nervous systems can be
      meaningfully sought. To do this, we have examined the distribution of serotonin
      (5-hydroxytryptamine)-like immunoreactive neurons in the central nervous system
      (CNS) of four common British isopods. Two species of terrestrial woodlouse,
      Oniscus asellus and Armadillidium vulgare, the littoral sea slater, Ligia
      oceanica, and the aquatic water hoglouse, Asellus meridianus, all possess
      approximately 40 pairs of serotonin-like immunoreactive neurons, distributed
      throughout the CNS in a very similar pattern. Interspecific homology is clearly
      suggested. Serotonin-like immunoreactive neurons in the first (T1) and fourth
      (T4) thoracic ganglia are particularly prominent in each of the four species
      studied. Whole-mount immunohistochemistry shows that the pair of T1 neurons have
      large dorsolateral cell bodies and prominent neurites that project medially and
      then anteriorly, whereas the pair of T4 neurons have ventrolateral cell bodies
      and neurites that bifurcate to form a thin axon projecting anteriorly to
      terminate in T3 and a thick medial axon that projects posteriorly into the
      abdominal neuromeres of the terminal ganglion. Intracellular cobalt staining of
      these neurons reveals more of their arborizations: the T1 neurons send three
      processes anteriorly, which arborize in the brain and exist from the CNS via
      peripheral nerves, whereas the T4 neurons contribute considerably to the
      extensive pattern of serotonin-like immunoreactive fibres in T3-T6 ganglia. The
      overall pattern of serotonin-like immunoreactive neurons in the isopods is
      similar to that in decapod crustacea, and a number of putative homologies can be
      assigned. It is more difficult to homologize the isopod serotonin-like
      immunoreactive neurons with those in the insect CNS, but some stained brain and
      thoracic neurons share common cell body positions and axon trajectories in
      isopods, decapods, and insects and may therefore be homologous.

PMID- 7814676
TI  - Immunocytochemical evidence for the presence of Met-enkephalin and Leu-enkephalin
      in distinct neurons in the brain of the elasmobranch fish Scyliorhinus canicula.
AB  - Immunohistochemical methods have been used to investigate the distribution of
      various opioid peptides derived from mammalian proenkephalin in the central
      nervous system of Scyliorhinus canicula. The results indicate that both Leu- and
      Met-enkephalin-immunoreactive peptides are present in the dogfish brain. In
      contrast, enkephalin forms similar to Met-enkephalin-Arg-Phe or Met-enkephalin
      Arg-Gly-Leu, and mammalian alpha-neo-endorphin, dynorphin A (1-8), dynorphin A (1
      13), and dynorphin A (1-17) were not detected. Met- and Leu-enkephalin
      immunoreactivities were found in distinct neurons of the telencephalon and
      hypothalamus. In particular, cell bodies reacting only with the Met-enkephalin
      antiserum were localized in the preoptic nucleus and in the suprachiasmatic
      region of the hypothalamus. Conversely, cell bodies reacting only with the Leu
      enkephalin antiserum were localized in the pallium and the nucleus lobi lateralis
      hypothalami. Several areas of the telencephalon and diencephalon exhibited both
      Met- and Leu-enkephalin-like immunoreactivity, but the two immunoreactive
      peptides were clearly contained in distinct perikarya. The overall distribution
      of Met-enkephalin-immunoreactive elements in the dogfish exhibited similarities
      to the distribution of proenkephalin-derived peptides previously reported for the
      brain of tetrapods. The fact that Met- and Leu-enkephalin-like peptides were
      detected in distinct neurons, together with the absence of dynorphin-related
      peptides, suggests the existence of a novel Leu-enkephalin-containing precursor
      in the dogfish brain.

PMID- 7814677
TI  - Comparative distribution of N-acetylaspartylglutamate and GAD67 in the cerebellum
      and precerebellar nuclei of the rat utilizing enhanced carbodiimide fixation and
      immunohistochemistry.
AB  - The most prevalent peptide in the nervous system, N-acetylaspartylglutamate
      (NAAG), specifically activates N-methyl D-aspartate (NMDA) receptors and a
      subclass of metabotropic glutamate receptors. One action of this peptide may be
      to modulate the release of other neurotransmitters, including gamma-aminobutyric
      acid (GABA). The present study describes the cellular distribution of NAAG,
      relative to GABA, in the cerebellum and precerebellar nuclei as a foundation for
      further physiological investigations. Numerous cells of origin for mossy fibers,
      including many of the larger neurons of the pontine nuclei, lateral reticular
      nuclei, vestibular nuclei, reticulotegmental nuclei, and spinal grey, were
      moderately to strongly stained for NAAG. Many NAAG-labeled fibers were clearly
      visible in the cerebellar peduncles and central white matter. Mossy fibers and
      mossy endings were among the most prominent NAAG-immunoreactive elements in the
      cerebellar cortex. Most neurons in the inferior olive were not stained for NAAG,
      and only sparse, lightly immunoreactive, climbing fiber-like endings could be
      identified in restricted regions of the cortical molecular layer. Purkinje
      neurons ranged from nonreactive to moderately positive, with the great majority
      being unstained. Cerebellar granule cells did not exhibit any NAAG
      immunoreactivity. A population of neurons in the deep cerebellar nuclei was
      highly immunoreactive for NAAG. Additionally, many neurons of the red nucleus
      were intensely stained for NAAG. Comparisons with staining for the 67 kD form of
      glutamic acid decarboxylase in serial sections revealed complementary
      distributions, with NAAG in excitatory pathways and cell groups, and glutamic
      acid decarboxylase in inhibitory systems. These findings suggest a significant
      functional involvement of NAAG in the excitatory afferent and efferent projection
      systems and provide an anatomical basis for investigations into the interactions
      of NAAG and GABA in the cerebellum.

PMID- 7814678
TI  - Distribution and morphology of sacral spinal cord neurons innervating pelvic
      structures in Xenopus laevis.
AB  - Relatively little is known about the organization of neural input to pelvic
      viscera in amphibia. In this study, sacral spinal efferent neurons were labeled
      in Xenopus laevis frogs by application of horseradish peroxidase (HRP) to the
      tenth spinal nerve, to pelvic musculature, or to the pelvic nerve. DiI was
      applied to the pelvic nerve with similar results. Labeled spinal neurons were
      located in the intermediate gray or in the ventral horn. Neurons in the tenth
      dorsal root ganglion, but not in the spinal cord, were labeled after application
      of HRP or DiI to the pudendal nerve. The labeled neurons in the spinal cord
      intermediate gray were in a position comparable to that of the mammalian sacral
      parasympathetic nucleus (SPN). Two apparent subdivisions included 1) a medial
      cluster of cells with mediolaterally oriented dendrites and 2) a lateral group
      with dorsoventrally oriented dendrites. An intermediate group, not clearly
      classed with the other two, was also identifiable. In some cases, labeled tenth
      nerve primary afferents were seen in contact with efferent neurons of the
      intermediate gray. Labeled neurons in the ventral horn medial to the lateral
      motor column were small, with dendrites oriented mediolaterally, in a position
      comparable to that of the mammalian Onuf's nucleus. The peripheral targets of DiI
      labeled pelvic nerve axons were the compressor cloaca muscle, cloaca, and
      bladder. DiI-labeled pudendal nerve axons distributed peripherally to cloacal lip
      and medial thigh integument. These data suggest that the pudendal nerve in
      amphibians is purely sensory and that both somatic and autonomic motor axons
      traverse the pelvic nerve.

PMID- 7814679
TI  - Organization of projections from the anterior hypothalamic nucleus: a Phaseolus
      vulgaris-leucoagglutinin study in the rat.
AB  - Anterior hypothalamic nucleus (AHN) projections were examined with the Phaseolus
      vulgaris-leucoagglutinin (PHA-L) method in adult male rats. Labeled axons from
      the AHN follow three major routes. 1) A large ascending pathway ends densely in
      the telencephalon, particularly in the lateral septal nucleus. Axons along this
      route provide moderate to dense input to the medial and lateral preoptic areas,
      and a few are also observed in the septofimbrial nucleus and fimbria; the latter
      end in the temporal hippocampus. A few axons reach the amygdala through the bed
      nuclei of the stria terminalis, which receive a moderate input, and then the
      stria terminalis, and others reach it by way of the ansa peduncularis. 2) The
      second pathway travels dorsal to the AHN, ending densely in rostral perifornical
      regions of the lateral hypothalamic area, and the rostral ventrolateral tip of
      the nucleus reuniens. The parataenial and rostral paraventricular thalamic nuclei
      also receive a significant input. Some fibers and boutons were also observed in
      the rhomboid, interanterodorsal, and mediodorsal nuclei, and others course
      through the stria medullaris to the lateral habenula. 3) the largest pathway
      descends through dorsal and ventral routes in the medial hypothalamic zone before
      ending massively in the periaqueductal gray. Dorsal route fibers provide inputs
      to the zona incerta and posterior hypothalamic nucleus, whereas more ventral
      axons generate dense terminal fields in the ventromedial nucleus capsule and
      core, and dorsal premammillary nucleus. The retrochiasmatic area, dorsomedial
      nucleus, and medial supramammillary nucleus also receive significant inputs, and
      a few axons end in the subparafascicular nucleus, superior colliculus, and
      mammillary body. The caudalmost axons were seen in the pontine central gray and
      reticular formation. These pathways are bilateral, usually with a distinct
      ipsilateral predominance. The overall pattern of efferents from anterior,
      central, and posterior parts of the AHN is similar, whereas the relative
      densities of particular terminal fields may vary considerably. Projections from
      adjacent parts of the retrochiasmatic and perifornical areas are also described.
      The results are discussed in terms of neural circuitry that may be involved in
      mediating interactions between animals.

PMID- 7814680
TI  - Effect of altered neuronal activity on cell size in the medial nucleus of the
      trapezoid body and ventral cochlear nucleus of the gerbil.
AB  - Activity-dependent transneuronal regulation of neuronal soma size has been
      studied in the medial nucleus of the trapezoid body and ventral cochlear nucleus
      of adolescent gerbils. Cochlear ablation or tetrodotoxin has been used to
      eliminate afferent electrical activity in auditory nerve fibers permanently or
      for 24 or 48 hours. Previous studies have shown that the cross-sectional area of
      spherical cell somata in the ipsilateral anteroventral cochlear nucleus decreases
      within 24 hours of electrical activity blockade with tetrodotoxin, which is fully
      reversible when activity is restored. The present findings extend this work by
      directly comparing the results of unilateral blockade of auditory nerve action
      potentials or unilateral cochlear ablation on the size of spherical and globular
      cell bodies in the ventral cochlear nucleus with changes produced by the same
      manipulations in third-order cells, principal neurons in the medial nucleus of
      the trapezoid body. Soma size in both ventral cochlear nucleus cell types
      decreases reliably by 24 hours after cochlear removal or eighth nerve activity
      blockade by tetrodotoxin. Soma size of neurons in the contralateral medial
      nucleus of the trapezoid body decreases 48 hours, but not 24 hours, after either
      manipulation. When activity in auditory nerve fibers is allowed to resume for 7
      days following a 48-hour activity blockade, soma size fully recovers in the
      medial nucleus of the trapezoid body as well as in ventral cochlear nucleus
      neurons. We also report that the cross-sectional area of neuronal soma in the
      medial nucleus of the trapezoid body is larger in lateral regions of medial
      nucleus of the trapezoid body (low-frequency representation) than in the medial
      regions of the nucleus (high-frequency representation). We conclude that cell
      body size changes in brainstem auditory neurons are reversible and that the
      signals associated with the loss and subsequent recovery of soma size are
      activity related. However, the delayed effect of activity deprivation in the
      medial nucleus of the trapezoid body suggests that trophic substances released by
      afferent axons may contribute to the maintenance of anatomical characteristics.

PMID- 7814681
TI  - Morphology and synaptic connections of slowly adapting periodontal afferent
      terminals in the trigeminal subnuclei principalis and oralis of the cat.
AB  - Previous studies suggest that sensory information from primary afferent fibers is
      processed in a distinct manner in the individual subnuclei of trigeminal sensory
      nuclear complex. The present study has addressed this issue by using intra-axonal
      labeling with horseradish peroxidase to examine the ultrastructure and synaptic
      organization of axon terminals from slowly adapting (SA) periodontal afferents in
      the ventral subdivision (Vpv) of principalis and the rostro-dorsomedial part
      (Vo.r) of oralis. Our observations are based on complete or near-complete
      reconstructions of 139 synaptic boutons in Vpv and 105 in Vo.r. All the labeled
      boutons contained clear, spherical, synaptic vesicles and were presynaptic to
      unlabeled dendrites, and they were frequently postsynaptic to unlabeled axon
      terminals containing pleomorphic synaptic vesicles (P-endings). The P-endings
      frequently formed axodendritic synapses on dendrites which received axodendritic
      synapses from labeled boutons (synaptic triads). On the basis of the number of
      contacts, synaptic arrangements associated with the labeled boutons could be
      subgrouped into simple (one or two contacts), intermediate (three or four
      contacts), and complex (five or more contacts) types. The labeled boutons varied
      from round to elongated forms with smooth to more irregular or scalloped
      contours. The boutons with scalloped contour were much more frequent in the
      complex type. The boutons of the intermediate type were significantly smaller
      than the complex type and larger than the simple type. The SA periodontal
      afferent terminals participated in each type of synaptic arrangements in Vpv, but
      were mostly of the simple type in Vo.r. The size of labeled boutons was
      significantly larger in Vpv than in Vo.r. The total number of axodendritic and
      axoaxonic contacts per labeled bouton was significantly higher in Vpv than in
      Vo.r. Another difference was the more frequent occurrence of synaptic triads in
      Vpv than in Vo.r. These observations provide evidence that sensory information
      from primary afferent fibers is processed in a different manner in the two
      subnuclei.

PMID- 7814682
TI  - Postnatal development of parvalbumin immunoreactivity in the cerebral cortex of
      the cat.
AB  - Parvalbumin immunoreactivity in the developing neocortex of the cat progresses
      following specific laminar, areal, and, in a particular area, roughly
      anteroposterior gradients. Parvalbumin immunoreactivity first occurs in basket
      cells and later in chandelier neurons. Pyramid-like immunoreactive neurons are
      also transitorily observed from the second to the third week in layer V of the
      auditory association-related areas. Parvalbumin-immunoreactive neurons first
      appear in the primary somatosensory cortex and primary auditory and visual areas,
      followed by the primary motor and polysensory association areas and, finally, the
      auditory association areas and cortical areas related to the limbic system. In
      addition to cortical neurons, three fiber systems are immunolabeled with
      antiparvalbumin antibodies: thalamocortical, callosal, and ipsilateral
      corticocortical. Parvalbumin-immunoreactive thalamocortical fibers appear during
      the first month of postnatal life. Parvalbumin-immunoreactive callosal and
      ipsilateral corticocortical fibers are seen from the fourth postnatal week
      onward. Because all parvalbumin-immunoreactive cortical neurons in adulthood are
      nonpyramidal inhibitory cells, the present findings suggest that a number of
      ipsilateral corticocortical and callosal connections may be inhibitory.

PMID- 7814683
TI  - Small subclass of rat olfactory neurons with specific bulbar projections is
      reactive with monoclonal antibodies to the HSP70 heat shock protein.
AB  - As part of a study of turnover of rat olfactory receptor neurons we have been
      examining immunohistochemical expression of members of the 70 kD heat shock
      protein (HSP70) family in the olfactory epithelium. Expression of HSP70 family
      members is up-regulated in many cells following exposure to physiologically
      stressing conditions. Because dying neurons are likely to undergo some sort of
      physiological stress before the onset of frank degeneration, we hoped that anti
      HSP70 monoclonal antibodies would prove to be useful markers for early stages of
      olfactory neuron cell death. Two anti-human HSP70 monoclonal antibodies were
      used, Mabs 2A4 and 3a3. Two-dimensional gel electrophoresis/western blot analysis
      indicates that these Mabs are reactive with the HSC70 and HSP70 members of the
      rat HSP70 family. Immunohistological observations show that both Mabs are
      strongly reactive with a widely dispersed subpopulation of olfactory receptor
      neurons. Morphological, immunohistological, and autoradiographic birthdating
      analyses demonstrate that reactive cells are fully mature receptor neurons. Their
      reactivity, however, does not appear to be stress-related. More significantly,
      axons of reactive neurons show intense anti-2A4 reactivity. This has allowed us
      to trace these axons to their target glomeruli in the olfactory bulb,
      demonstrating that the reactive neurons project to just one to two glomeruli on
      either side of each bulb via consistent and predictable pathways. This is the
      first subpopulation of olfactory receptor neurons to be traced to such a small
      number of glomeruli. Given this extremely small number, it seems likely that the
      reactive receptor cell subpopulation serves some specific olfactory function. In
      addition, axonal 2A4 reactivity should also prove useful in defining the relative
      roles of receptor neurons and glomeruli in the establishment of epithelial
      glomerular connections.

PMID- 7814684
TI  - Organization of projections from the ventromedial nucleus of the hypothalamus: a
      Phaseolus vulgaris-leucoagglutinin study in the rat.
AB  - The organization of projections from the four parts of the ventromedial nucleus
      (VMH) and a ventrolaterally adjacent region tentatively identified as the tuberal
      nucleus (TU) have been analyzed with small injections of the anterograde axonal
      tracer Phaseolus vulgaris-leucoagglutinin (PHA-L). Extrinsic and intranuclear
      projections of each part of the VMH display clear quantitative differences,
      whereas the overall patterns of outputs are qualitatively similar. Overall, the
      VMH establishes massive intrahypothalamic terminal fields in other parts of the
      medial zone, tending to avoid the periventricular and lateral zones. The
      ventrolateral VMH is more closely related to other parts of the hypothalamus that
      also express gonadal steroid hormone receptors, including the medial preoptic,
      tuberal, and ventral premammillary nuclei, whereas other parts of the VMH are
      more closely related to the anterior hypothalamic and dorsal premammillary
      nuclei. All parts of the VMH project to the zona incerta (including the A13
      region) and parts of the midline thalamus, including the paraventricular and
      parataenial nuclei and nucleus reuniens. The densest inputs to the septum are to
      the bed nuclei of the stria terminalis, where the ventrolateral and central VMH
      innervate the anteroventral and anterodorsal areas and transverse and
      interfascicular nuclei, whereas the anterior and dorsomedial VMH innervate the
      latter two. The central, lateral, and medial amygdalar nuclei receive substantial
      inputs from various parts of the VMH. Other regions of the telencephalon,
      including the nucleus accumbens and the piriform-amygdaloid, infralimbic,
      prelimbic, anterior cingulate, agranular insular, piriform, perirhinal,
      entorhinal, and postpiriform transition areas, also receive sparse inputs. All
      parts of the VMH send a massive, topographically organized projection to the
      periaqueductal gray. Other brainstem terminal fields include the superior
      colliculus, peripeduncular area, locus coeruleus, Barrington's nucleus,
      parabrachial nucleus, nucleus of the solitary tract, and the mesencephalic,
      pontine, gigantocellular, paragigantocellular, and parvicellular reticular
      nuclei. The projections of the TU are similar to, and a subset of, those from the
      VMH and are thus not nearly as widespread as those from adjacent parts of the
      lateral hypothalamic area. Because of these similarities, the TU may eventually
      come to be viewed most appropriately as the lateral component of the VMH itself.
      The functional implications of the present findings are discussed in view of
      evidence that the VMH plays a role in the expression of ingestive, affective, and
      copulatory behaviors.

PMID- 7814685
TI  - Crustacean cardioactive peptide-immunoreactive neurons in the ventral nervous
      system of crayfish.
AB  - Crustacean cardioactive peptide-immunoreactive neurons have been mapped in whole
      mount preparations and sections of the ventral nervous system of the crayfish
      Astacus astacus and Orconectes limosus. Based on their morphology, projection
      patterns, and staining characteristics, two types of contralaterally projecting
      neurons are individually identifiable. In both species, these neurons occur in
      all neuromers as apparent serial homologs. In adult specimens, one type of cell
      has a small, densely stained dorsal lateral perikaryon, and a descending axon,
      and appears to be an interneuron. Each neuromer contains a single pair of these
      cells. Only in maxillary ganglia, these cells may have an additional ascending
      projection. The other type, a neurosecretory cell, has a larger, weakly stained
      perikaryon and a projection to the segmental third root of the next anterior
      neuromer. All neuromers contain a single pair of these neurons adjacent to the
      interneurons except for the abdominal neuromers, which contain two pairs of the
      neurosecretory cells. Central arborizations and varicose processes toward the
      surface of the third roots and within the perineural sheath of the ventral nerve
      cord arise from these neurons. Electron microscopy of granule-containing
      terminals substantiated that these newly discovered extensive neurohemal areas
      are release sites for the peptide. In young immature specimens, the perikarya of
      both neuron types do not differ in size. Additional weakly stained small
      perikarya occur in all neuromers of Astacus astacus. These two types of crayfish
      neurons and other comparable aminergic and peptidergic neurons of crayfish and
      lobster are differentially distributed in the ventral cord. Furthermore,
      comparison of similar neuron types in crab, locust, meal worm, and moth species
      indicates intra- and interphyletic structural homologies.

PMID- 7814686
TI  - Loss of dopamine D2 receptors varies along the rostrocaudal axis of the
      hippocampal complex in Alzheimer's disease.
AB  - The anatomy of the hippocampus, including the organization of its intrinsic
      neural circuits and afferents, is organized along a rostrocaudal axis. Dopamine
      D2 receptors are expressed in specific regions of the hippocampal complex
      (hippocampal subfields, entorhinal cortex, perirhinal cortex) and show
      differential expression along this axis. The dentate gyrus and CA3/CA4 subfields
      show higher numbers of D2 receptors in the rostral than in the caudal levels. In
      contrast, the subiculum shows the reverse gradient. We report here that
      Alzheimer's disease (AD) is associated with reduced expression of the dopamine D2
      receptor, but the effects differ with respect to the rostrocaudal axis and area
      within the hippocampal complex. The number of D2 receptors is significantly
      reduced in the molecular layer of the dentate gyrus, CA3 subfield, and subiculum.
      For the dentate gyrus and subiculum, there were greater losses at more rostral
      levels. The CA3/CA4 subfields showed the greatest losses caudally. The entorhinal
      cortex, which shows only modest expression of D2 receptors in controls, does not
      exhibit reduced numbers in AD. The external laminae of the rostral perirhinal
      cortex showed more significant losses than more caudally in this cortical field.
      The regions showing loss of D2 receptors do not typically contain neuritic
      plaques, neurofibrillary tangles, or significant neuron loss. Thus other
      mechanisms must account for the unique gradient of D2 receptor loss in the
      hippocampus. The regions of reduced expression of dopamine D2 receptors do
      correlate well with the terminal zone of the dentate association pathway, the
      afferents from the amygdala and perirhinal cortex, and the sources of those
      afferents within the amygdala and perirhinal cortex. The specific patterns of
      reduced D2 receptor expression in AD are likely to contribute significantly to
      the disrupted information flow into and out of the hippocampus and, thus, of
      functions subserved by this system.

PMID- 7814687
TI  - Hypoxia and electrical stimulation of the carotid sinus nerve induce Fos-like
      immunoreactivity within catecholaminergic and serotoninergic neurons of the rat
      brainstem.
AB  - A complete understanding of the neural mechanisms responsible for the
      chemoreceptor and baroreceptor reflexes requires precise knowledge of the
      locations and chemical phenotypes of higher-order neurons within these reflex
      pathways. In the present study, the protein product (Fos) of the c-fos
      protooncogene was used as a metabolic marker to trace central neural pathways
      following activation of carotid sinus nerve afferent fibers. In addition,
      immunohistochemical double-labeling techniques were used to define the chemical
      phenotypes of activated neurons. Both electrical stimulation of the carotid sinus
      nerve and physiological stimulation of the carotid bodies by hypoxia induced Fos
      like immunoreactivity in catecholaminergic neurons containing tyrosine
      hydroxylase or phenylethanolamine-N-methyltransferase in the ventrolateral
      medulla oblongata and, to a lesser degree, in the dorsal vagal complex. Tyrosine
      hydroxylase/Fos colocalization was also observed in the locus coeruleus and the
      A5 noradrenergic cell group in pons. Many serotoninergic neurons in nucleus raphe
      pallidus, nucleus raphe magnus, and along the ventral medullary surface contained
      Fos-like immunoreactivity. In pons and midbrain, Fos-like immunoreactivity was
      observed in the lateral parabrachial and Kolliker-Fuse nuclei, the inferior
      colliculus, the cuneiform nucleus, and in the vicinity of the Edinger-Westphal
      nucleus, but no catecholaminergic or serotoninergic colocalization was observed
      in these regions. Although Fos-labeled cells were observed within and lateral to
      the dorsal raphe nucleus, few were catecholaminergic or serotoninergic. This
      study further defines a potential central neuroanatomical substrate for the
      chemoreceptor and/or baroreceptor reflexes.

PMID- 7814688
TI  - Development of microglia in the quail optic tectum.
AB  - The development of microglia in the quail optic tectum from embryonic day 6 to
      adulthood was studied by using the QH1 monoclonal antibody. In youngest tecta,
      microglial cells were scarcely present, but their number rose in subsequent
      stages. A clear pattern of microglial cell distribution was observable in embryos
      of 9-16 days. (1) Round cells appeared close to the ventricular layer. (2) Large
      numbers of ameboid and round labeled cells were seen in the stratum album
      centrale during development. A gradient of cell density was observable in this
      layer, as fewer labeled cells appeared in medial regions of the tectum than in
      lateral regions. (3) Maturing ramified cells were found in layers external to the
      stratum album centrale, where they increased in number and in branching
      complexity during development. In adult tecta, almost all microglial cells were
      of the mature ramified type and were distributed homogeneously in the different
      tectal layers, although in some layers they had particular morphological
      features. The distribution of microglia in the developing tectum and in adjacent
      regions provided insight into the routes of microglial cell invasion of the
      tectum during development. Apparently, a proportion of microglial cells reached
      the tectal parenchyma from the meninges and from the ventricular lumen, but the
      majority of them migrated along nerve fiber tracts from their entry point at the
      pial surface of the ventromedial caudal tectum. After they reached the stratum
      album centrale, microglial cells continued their migration toward more external
      layers, where they differentiated into ramified microglia.

PMID- 7814689
TI  - Developmental changes in the laminar termination of A fibre cutaneous sensory
      afferents in the rat spinal cord dorsal horn.
AB  - In order to establish the specificity of growth and termination of dorsal root
      afferents within the developing spinal cord, the central dorsal horn terminals of
      myelinated sensory afferents were labelled at various stages in the rat from
      embryonic day (E)18 through to postnatal day (P) 35 using horseradish peroxidase
      conjugated to choleragenoid (B-HRP). The preferential labelling of A fibre
      afferents with this tracer was found to be as clear in the neonate as has been
      reported for the adult. The results show that while the somatotopic arrangement
      of A fibre afferent terminals in the dorsal horn is established early in
      development, the laminar projections are not. Following peripheral nerve or local
      skin injections of B-HRP, A fibre terminals were found to project throughout
      laminae I to V, including lamina II (substantia gelatinosa). This widespread
      termination was observed consistently until the end of the third postnatal week.
      After P22 the terminal field becomes restricted to the normal laminae III to V.

PMID- 7814690
TI  - Immunocytochemical localization of amyloid precursor protein in rat brain.
AB  - The localization of amyloid precursor protein (APP) in rat brain was studied with
      a cytoplasmic domain-specific antibody. Light microscopic immunocytochemistry
      demonstrated that APP is present in most neurons, in some oligodendrocytes, and
      in a population of cells with diameters less than 10 microns that may be glial.
      Marked differences in immunoreactivity among neurons were observed, and the
      strongest immunoreactivity was contained in larger neurons. Neurons with scant
      cytoplasm, such as granule cells in the olfactory bulb, dentate gyrus, and
      cerebellum, were weakly immunoreactive. Differences in neuropil immunoreactivity
      were also observed; this type of staining was strongest in the caudatoputamen,
      lateral septum, medial habenula, nucleus reticularis of the dorsal thalamus, and
      the lateral portion of the ventroposterior nucleus. Neuropil immunostaining was
      weakest in layer IV of cortex and in areas containing granule cells. The fact
      that APP seems to be present in the vast majority of neurons suggests that this
      protein plays a role common to all neurons. The fact that there is a great
      difference in the steady-state amount of APP among different types of neurons
      suggests that APP may play a specific role in the function of certain classes of
      neurons.

PMID- 7814691
TI  - Physiology and morphology of complex spiking neurons in the guinea pig dorsal
      cochlear nucleus.
AB  - Intracellular recordings from the dorsal cochlear nucleus have identified cells
      with both simple and complex action potential waveforms. We investigated the
      hypothesis that cartwheel cells are a specific cell type that generates complex
      action potentials, based on their analogous anatomical, developmental, and
      biochemical similarities to cerebellar Purkinje cells, which are known to
      discharge complex action potentials. Intracellular recordings were made from a
      brain slice preparation of the guinea pig dorsal cochlear nucleus. A
      subpopulation of cells discharged a series of two or three action potentials
      riding on a slow depolarization as an all-or-none event; this discharge pattern
      is called a complex spike or burst. These cells also exhibited anodal break
      bursts, anomalous rectification, subthreshold inward rectification, and frequent
      inhibitory postsynaptic potentials (IPSPs). Seven complex-spiking cells were
      stained with intracellular dyes and subsequently identified as cartwheel neurons.
      In contrast, six identified simple-spiking cells recorded in concurrent
      experiments were pyramidal cells. The cartwheel cell bodies reside in the lower
      part of layer 1 and the upper part of layer 2 of the nucleus. The cells are
      characterized by spiny dendrites penetrating the molecular layer, a lack of basal
      dendritic processes, and an axonal plexus invading layers 2 and 3, and the inner
      regions of layer 1. The cartwheel cell axons made putative synaptic contacts at
      the light microscopic level with pyramidal cells and small cells, including
      stellate cells, granule cells, and other cartwheel cells in layers 1 and 2. The
      axonal plexus of individual cartwheel cells suggests that they can inhibit cells
      receiving input from either the same or adjacent parallel fibers and that this
      inhibition is distributed along the isofrequency contours of the nucleus.

PMID- 7814692
TI  - Patterning of the neocortical projections from the raphe nuclei in perinatal
      rats: investigation of potential organizational mechanisms.
AB  - Serotoninergic (5-HT) fibers in the cerebral cortex of perinatal rats have a
      pattern that coincides with the boundaries of primary sensory areas and within
      the primary somatosensory cortex form the rattunculus. This patterned
      immunoreactivity (IR) appears about 60 hours after birth and disappears between
      postnatal days (P-) 12 and 15. Three experiments were carried out to evaluate
      mechanisms that might underlie the precise patterning of the 5-HT-IR. Retrograde
      labelling with fluorescent tracers in perinatal rats revealed only a coarse
      rostrocaudal topography in the raphe-cortical projection and the existence of
      raphe cells projecting to multiple cortical locations. Thus, a precise point-to
      point, raphe-cortical projection does not underlie the patterned cortical 5-HT
      IR. Ablation of the thalamus prior to the age at which patterned 5-HT-IR could be
      seen in the developing cortex caused a complete loss of patterned
      immunoreactivity. This suggests that 5-HT fibers may require the presence of
      thalamocortical axons to achieve the pattern observed in normal animals.
      Serotoninergic raphe neurons transplanted to the cortices of newborn rats
      exhibited extensive axonal outgrowth, but did not form a somatotopic pattern.
      This result also suggests that specific spatiotemporal interactions between
      growing 5-HT and thalamocortical axons may be necessary for the somatotopic
      patterning of the former fibers.

PMID- 7814693
TI  - Distribution of Purkinje cell-specific Zebrin-II/aldolase C immunoreactivity in
      the mouse, rat, rabbit, and human retina.
AB  - The developmental, genetic, and biochemical similarities that have been observed
      between the cerebellum and retina form the basis for ongoing investigations into
      retinal expression of cerebellar-specific proteins. We have examined the mouse,
      rat, rabbit, and human retina for expression of a protein that is present in
      parasagittal Purkinje cell strips and that is recognized by the antibody Zebrin
      II. This protein has recently been identified as a member of the aldolase C
      isoenzymes. Western blotting and immunocytochemistry have been used. The
      monoclonal antibody Zebrin-II recognized a prominent 36 kDa protein band on
      immunoblots of both the cerebellum and the retina of the examined species.
      Immunocytochemistry showed that, in the three nonhuman species, cells were
      stained in the ganglion cell layer (GCL). In addition, in the mouse and rabbit,
      cells in the inner nuclear layer (INL) were also labeled. Except for the visual
      streak, there were more immunopositive cells in the rabbit GCL and INL than in
      corresponding areas of the mouse retina. In the human, in contrast to the other
      species, the photoreceptor cell layer was strongly aldolase C immunoreactive. In
      all species except for the rat, the photoreceptor inner segments also displayed a
      weak labeling. The results show that this aldolase C isoenzyme is another protein
      that is selectively expressed by the cerebellum and retina. Furthermore, the
      retinal expression is species specific, and this pattern seems to show a good
      correlation with the oxygenation level of the individual compartments. The
      indication that this aldolase C isoenzyme has specific developmental functions in
      the retina provides additional clues for our understanding of cerebellar
      organization.

PMID- 7814695
TI  - Good Sams.

PMID- 7814696
TI  - Thinking about tomorrow for nursing: changes and challenges.
AB  - Many changes will be forthcoming in planning and implementing nursing practice in
      community-based settings in the future. Nursing education will experience major
      challenges in planning and developing curricula as a response to more mature
      people becoming nurses for the first time. Clinical practice "without walls," a
      change from what we have traditionally known, will require creative approaches
      toward bringing nurse colleagues along who have only practiced in institutions.
      This article is intended to stimulate new ideas and solutions for nursing to meet
      new challenges brought on by health care reform.

PMID- 7814697
TI  - Nursing documentation: a program to promote and sustain improvement.
AB  - Pertinent, timely, and accurate nursing documentation promotes consistency in
      client care and effective communication among nurses and other health team
      members. Alternative documentation systems, continuing education efforts, and
      ongoing quality management activities are necessary to ensure that standards of
      record keeping are maintained. A pilot project using such methods was conducted
      on two hospital units to promote adherence to a specific documentation system.
      Education was integrated with peer auditing and follow-up over a 6-month period.
      The nursing staff significantly improved the quality of their documentation and
      sustained this improvement over time. Staff's knowledge about documentation
      improved significantly. Furthermore, there was a statistically significant
      decrease in documentation errors. The integration of peer auditing and continuing
      education enabled nurses to attain and maintain specific documentation standards.

PMID- 7814694
TI  - Topography of developing thalamic and cortical pathways in the visual system of
      the cat.
AB  - Adult patterns of connectivity could emerge during development by a process of
      selective elimination from an earlier, more widespread, connectivity. We have
      addressed this issue by examining the topography of developing projections to
      area 17 in the cat. At different postnatal ages, paired injections of the
      retrograde tracers diamidino yellow and fast blue were made in area 17.
      Interinjection separations were carefully controlled and the spatial distribution
      of the two populations of labelled neurones investigated. Projections to the
      striate cortex from the lateral geniculate nucleus, area 18, as well as
      connections intrinsic to area 17 were analysed quantitatively with a graphic
      method that uses a two-dimensional model of the projection. This allows two
      parameters of the projection to be calculated: the divergence (the spatial extent
      of area 17 contacted by an infinitely small region of an afferent structure) and
      the convergence (the extent of an afferent structure that projects to an
      infinitely small region of area 17). During postnatal development, the bulk of
      the connections making up the geniculostriate and corticocortical pathways showed
      no variation either in their convergence and divergence. However, the projection
      of area 18 to area 17 and the intrinsic area 17 connections (but not the
      geniculostriate projection) in the 3-15-day-old kittens were each found to
      contain a small subpopulation of widely scattered neurones with widespread axonal
      trajectories. These results, showing that many initially formed connections
      display a high degree of topographical order, are discussed in terms of the
      control mechanisms specifying axonal trajectories during development.

PMID- 7814698
TI  - Teaching in the affective domain.
AB  - Elements of the affective domain encompass receiving, responding, valuing,
      organization, and characterization by a value or value complex. Nurse educators
      are taking a renewed look at affective education in light of a desire to prepare
      humanistic nurses who practice the art of caring. The teaching-learning climate
      necessary for effective implementation of affective instruction is addressed.
      Instructional methods including role play, case study, questioning, simulation
      gaming, values inquiry and values clarification are discussed as they relate to
      affective education.

PMID- 7814699
TI  - The communication training needs of registered nurses.
AB  - The purpose of this study was to determine registered nurses' (RN) perceived
      levels of communication effectiveness and need for communication training.
      Results of the survey indicate that RNs view themselves as fairly effective in
      using most job-related communication skills except for performance appraisal
      interviewing, public speaking, and persuasion. The majority of RNs had received
      training in most communication skills, the exceptions being persuasion and
      employment interviewing. The two most prominent sources for this training were
      college and on-the-job training. The results also indicate that RNs believe a
      variety of communication skills, including presentational speaking, listening,
      persuasive speaking, group problem solving, leadership, and technical report
      writing, are important to their job performance. The majority of RNs thought they
      needed additional training in these skills and were willing to receive such
      training. Their preferences for receiving the instruction were in-house or
      industry-based training seminars and profession-sponsored continuing education
      programs.

PMID- 7814700
TI  - RN to BS in nursing: historical review leads to articulation agreement.
AB  - Historically, registered nurses who have graduated from associate degree or
      diploma programs and who wish to obtain a baccalaureate degree in nursing have
      been required to pass challenge examinations to obtain credit for their previous
      nursing knowledge. A review of this university's policy regarding challenge
      examinations convinced faculty to establish a transition course and to actively
      pursue articulation agreements with local community colleges. Through these
      agreements, RN students would be granted 29 credits and bypass the junior year.
      This article is written to encourage others to review their policies to
      facilitate educational mobility for the RN/BS student.

PMID- 7814701
TI  - Preparing nurses for the inevitable: the New Madrid earthquake.
AB  - Although this article discusses earthquake preparedness for the New Madrid
      seismic zone, registered nurses in any location will be on the front line as
      patient caregivers and managers in the event of a damaging earthquake. Two self
      instructional modules were developed to educate registered nurses about
      earthquake preparedness. Statistical analyses of pretest and posttest scores from
      nurses who completed the modules and from nurses who participated in a control
      group reveal that the modules are effective educational tools. This information
      will make them more effective as nurses during and after an earthquake and
      emphasizes the need for their involvement in disaster mitigation and planning.

PMID- 7814702
TI  - How do older nurses perceive their clinical competence and the effects of age?
AB  - In 1996, the first of the baby boomer population bulge that includes registered
      nurses (RNs) will reach age 50. Considering the prevailing negative stereotypes
      about women, nurses, and older adults in general, it is necessary to understand
      the abilities and needs of older nurses. This qualitative study was the first
      stage of a needs assessment of professionally mature RNs. Eight female RNs,
      employed full-time in an acute care setting and over age 50, were interviewed to
      determine their perceptions, attitudes, and beliefs about their own professional
      competence and how they believed they were perceived by others. Results indicated
      that older RNs felt good about themselves and the profession, and valued
      traditional bedside nursing and professional behaviors. Of the eight recurring
      themes found, the need for continuing education generated the most discussion.
      Will the methods and resources of the past meet the educational needs of the
      older nurses? Further study is recommended to discover their needs and the needs
      of their employers.

PMID- 7814703
TI  - Absence of cholic acid 7 alpha-dehydroxylase activity in the strains of
      Lactobacillus and Bifidobacterium.
AB  - To investigate the presence of 7 alpha-dehydroxylase activity on bile acids in
      the bacterial strains of fermented milk products, 46 strains of Lactobacillus
      casei, Lactobacillus paracasei, Lactobacillus rhamnosus, Lactobacillus
      acidophilus, Lactobacillus gasseri, Bifidobacterium adolescentis, Bifidobacterium
      bifidum, Bifidobacterium breve, Bifidobacterium infantis, Bifidobacterium longum,
      Lactococcus lactis spp. lactis, and Streptococcus salivarius spp. thermophilus
      were tested for their ability to produce deoxycholic acid from cholic acid. The
      production of deoxycholic acid was quantitatively measured by
      radiochromatographic analysis in anaerobically prepared washed whole resting
      cells and by HPLC analysis in growing cultures. Resting whole cells from a
      positive control strain, Eubacterium lentum-like strain c-25, converted 81.7% of
      .2 mM cholic acid to deoxycholic acid and 3.7% to 7-keto-deoxycholic acid, when
      the cell suspension was incubated anaerobically at a concentration of 2 mg of
      protein/ml for 4 h at pH 7.3. However, none of the test strains investigated in
      this study was able to transform cholic acid under the same conditions. In
      growing cultures, 91.5% of 150 micrograms/ml of cholic acid was transformed to
      deoxycholic acid and 1.1% to 7-keto-deoxycholic acid by E. lentum-like c-25 after
      a 7-d anaerobic incubation. None of the test strains showed production of either
      deoxycholic acid or 7-keto-deoxycholic acid as growing cultures.

PMID- 7814704
TI  - Antimutagenicity of fermented milk.
AB  - Reconstituted nonfat dry milk was fermented by Lactobacillus helveticus CH65,
      Lactobacillus acidophilus BG2FO4, Streptococcus salivarius ssp. thermophilus CH3,
      Lactobacillus delbrueckii ssp. bulgaricus 191R, and by a mixture of the latter
      two organisms. The fermented milks were then freeze-dried, extracted in acetone,
      dissolved in dimethylsulfoxide, and assayed for antimutagenicity in the Ames test
      (Salmonella typhimurium TA 100) against N-methyl, N'-nitro, N-nitroso-guanidine,
      and 3,2'-dimethyl-4-amino-biphenyl. Dose-dependent activity was significant
      against both mutagens in all extracts. Maximal inhibitory activity against 3,2'
      dimethyl-4-aminobiphenyl and N-methyl, N'-nitro, N-nitroso-guanidine was 2- and
      2.7-fold greater, respectively, than that exhibited by extracts of unfermented
      milk. Extracts of milk fermented by L. delbrueckii ssp. bulgaricus 191R were
      examined further. Compounds that were responsible for activity against both
      mutagens were less soluble in aqueous solutions than in dimethylsulfoxide.
      Adjustment of milk fermented by L. delbrueckii ssp. bulgaricus 191R to pH 3, 7.6,
      or 13 prior to freeze-drying and acetone extraction did not significantly alter
      the activity specific for 3,2'-dimethyl-4-aminobiphenyl. In contrast, compounds
      with activity specific for N-methyl, N'-nitro, N-nitrosoguanidine were less
      extractable at pH 7.6. The weak antimutagenicity of unfermented milk was not
      increased by addition of 2% L-lactic acid.

PMID- 7814705
TI  - Effect of mesenteric vein infusion of propionate on splanchnic metabolism in
      primiparous Holstein cows.
AB  - Our objective was to assess the effects of increased propionate supply on gut and
      liver function in lactating cows. Four multicatheterized, primiparous cows (30.4
      +/- .5 kg/d of milk) were fed for ad libitum intake a diet of 50% alfalfa hay and
      50% concentrate (20.6 +/- 1.9 kg/d of DM, 226 +/- 21 MJ/d of metabolizable
      energy, and 611 +/- 56 g/d of N). Each cow received intramesenteric infusions of
      NaCl (control) or Na-propionate (150 mmol/h of a 2.5 M solution) in a reversal
      design. After 72 h of infusion, blood flow (by indicator dilution) and net flux
      (venoarterial differences multiplied by blood flow) were measured across portal
      drained viscera and the liver. Energy supply from feed consumed and from infusion
      was similar between treatments. Energy that was excreted as milk decreased with
      propionate infusion. Propionate infusion increased arterial concentration of
      propionate; decreased absorption of acetate, butyrate, and valerate; and
      decreased hepatic removal of L-lactate, butyrate, valerate, NEFA, and oxygen.
      Propionate infusion decreased splanchnic release of glucose and increased
      splanchnic release of acetate and alanine. Net flux of urea, BHBA, insulin, or
      glucagon was unaffected by treatments. Our data show a link between a greater
      proportion of energy supplied as propionate and decreased energy excreted as
      milk. This response was associated with decreased net removal of glucogenic and
      ketogenic substrates by the liver and increased supply of acetate for use by
      peripheral tissues.

PMID- 7814707
TI  - Effects of clinical ketosis on test day milk yields in Finnish Ayrshire cattle.
AB  - A linear model for repeated measurements was used to estimate the effects of
      clinical ketosis on 722,198 test day milk yields collected from September 1, 1985
      to January 31, 1988 on 60,851 Finnish Ayrshire cows of parity < 7. An index was
      created to differentiate among milk collected within 17 d following diagnosis of
      ketosis, milk collected before or > 17 d after diagnosis, and milk collected on
      nonketotic cows. For each parity separately, the statistical model included fixed
      effects (ketosis, calving season, year and season of milk sampling, and stage of
      lactation) and random effects (herd and permanent and temporary environments) on
      test day milk yields. The pattern underlying correlations between temporary
      environmental effects was accommodated in the statistical model. Compared with
      those for nonketotic cows, lactation curves of cows with ketosis showed a
      depression in early lactation; estimated milk loss was 44.3 kg for 17 d after
      diagnosis. The 305-d milk yield of cows diagnosed with ketosis was estimated to
      be 141.1 kg higher than that of cows free of ketosis. Although milk losses
      occurred after ketosis, ketotic cows yielded more milk over the entire lactation
      than did nonketotic cows; and yields would have been even higher if cows had not
      had ketosis.

PMID- 7814706
TI  - Effect of graded levels of duodenal infusions of casein on mammary uptake in
      lactating cows. 2. Individual amino acids.
AB  - The experiment examined patterns of mammary uptake of individual AA when graded
      amounts of calcium caseinate (0, 177, 362, and 762 g/d) were infused duodenally
      into four lactating cows. Six blood samples were collected over 12 h from the
      subcutaneous abdominal vein and the carotid. Mammary blood flow was measured by
      an ultrasonic flow probe implanted around the external pudic artery. Infusions of
      casein linearly increased the arterial concentrations of all essential AA and
      several nonessential AA (Pro, Tyr, Orn, and Cit) and increased, or tended to
      increase, linearly the mammary arteriovenous differences of all AA except Glu and
      Ala. Absorption ability of the mammary gland was not reduced in vivo.
      Relationships between mammary arteriovenous differences and arterial
      concentrations were positive and linear in every cow for all AA except Asn, Ser,
      Gly, and Ala. Some essential AA (Lys, Arg, and branched-chain AA) were therefore
      taken up in excess of their output into milk proteins, but others (His, Thr, Met,
      and Phe) were almost exclusively extracted by the udder in a direct ratio to
      their output. As infusions of casein increase, Phe becomes probably the most
      critical AA for milk synthesis.

PMID- 7814708
TI  - Effects of in vivo administration of 1,25-dihydroxyvitamin D3 on in vitro
      proliferation of bovine lymphocytes.
AB  - Continuous infusion of 1,25-dihydroxyvitamin D3 in the bovine elevated 1,25
      dihydroxyvitamin D3 in plasma. Plasma 1,25-dihydroxyvitamin D3 remained elevated
      until infusions were discontinued. Increased 1,25-dihydroxyvitamin D3 was
      associated with hypercalcemia (11 to 12 mg/dl) that continued for several days
      postinfusion. Elevated 1,25-dihydroxyvitamin D3 also was associated with a
      significant 70% enhancement of lymphocyte proliferation in cells treated with
      concanavalin A. Cessation of infusion of 1,25-dihydroxyvitamin D3 resulted in the
      return of 1,25-dihydroxyvitamin D3 in plasma and lymphocyte proliferative
      response to preinfusion amounts. Proliferation in response to pokeweed mitogen
      was significantly inhibited on d 3 of infusions of 1,25-dihydroxyvitamin D3.
      Administration of parathyroid hormone for 4 d resulted in a sustained
      hypercalcemia (approximately 13 mg/dl) and a transient 1-d increase in 1,25
      dihydroxyvitamin D3 in plasma. Parathyroid hormone treatment generally did not
      affect the response of bovine lymphocytes to mitogen. In vivo elevation of 1,25
      dihydroxyvitamin D3 is either moderately immunostimulating or exerts no effect on
      mitogen-stimulated proliferation of lymphocytes. These results contrast with the
      in vitro results suggesting that 1,25-dihydroxyvitamin D3 is only
      immunosuppressive.

PMID- 7814709
TI  - Efficacy of dry cow therapy and a Propionibacterium acnes product in herds with
      low somatic cell count.
AB  - Dry cow therapy and a Propionibaterium acnes product were evaluated in four
      commercial herds with low SCC. Cows were randomly assigned within herds to
      treatment groups of approximately 90 cows receiving dry cow therapy, P. acnes,
      dry cow therapy plus P. acnes, or no treatment in a factorial arrangement. Each
      lactating quarter of cows that received dry cow therapy was infused via the teat
      duct with 300 mg of cephaprin at drying off. Cows that received P. acnes were
      infused intravenously with .4 mg of killed P. acnes at drying off, 7 to 10 d
      prepartum, and within 7 d after calving. A second prepartum injection of P. acnes
      immunostimulator was administered to cows that did not calve within 10 d after
      the first prepartum injection. Dry cow therapy enhanced bacteriological cures of
      IMI by Staphylococcus aureus and Corynebacterium bovis at drying off. Dry cow
      therapy reduced incidence of new IMI by environmental streptococci and C. bovis
      that originated during the dry period. Cows treated with P. acnes alone had a
      greater incidence of new IMI by Gram-negative bacilli originating during the dry
      period than did cows in the other treatment groups. Incidence of clinical
      mastitis at calving was greater for cows receiving no treatment than for cows
      receiving dry cow therapy, P. acnes, or dry cow therapy plus P. acnes.

PMID- 7814710
TI  - Effects of temperature and oxygen tension on growth of Escherichia coli in milk.
AB  - An in vitro system was developed to mimic conditions within normal and mastitic
      mammary glands. The system consisted of a modified batch fermenter that allowed
      for manipulation of temperature, oxygen tension, and pH. Experiments in tryptose
      soy broth and UHT-treated milk were conducted to evaluate growth characteristics
      of Escherichia coli P4 as physical conditions were manipulated. The effect of
      bacterial growth on oxygen tension and pH were also evaluated. Growth of E. coli
      was inhibited as temperature was increased from 37 to 41 degrees C and as oxygen
      tension was decreased from microaerophilic to anaerobic levels. At bacterial
      populations > 6 log10 cfu/ml, microaerophilic cultures became anaerobic. The pH
      followed a similar trend; however, after a significant decrease in pH, mean
      bacterial populations were 7.1 log10 cfu/ml in tryptosesoy broth and 8.2 log10
      cfu/ml in UHT-treated milk. This dynamic model demonstrated potential use in
      evaluation of growth characteristics of mammary gland pathogens in the lactating
      mammary gland.

PMID- 7814711
TI  - Efficacy of intramuscular oxytetracycline as a dry cow treatment for
      Staphylococcus aureus mastitis.
AB  - To determine the efficacy of intramuscular oxytetracycline as a supplemental dry
      cow treatment for Staphylococcus aureus mastitis, 37 Holstein cows were randomly
      assigned to two treatment groups: intracisternal infusion with a commercial
      preparation of cephapirin benzathine at drying off (20 cows) and infusion with
      cephapirin benzathine at drying off and intramuscular oxytetracycline at 11 mg/kg
      once daily on d 7, 8, 9, and 10 after drying off (17 cows). Milk samples
      collected 7, 14, 30, and 60 d after calving were plated for bacterial isolation
      within 24 h after collection and after 24 to 72 h of storage at -20 degrees C.
      Quarters were defined as infected if S. aureus was isolated from the fresh and
      frozen cultures from any one sample collected before drying off. An infected
      quarter was defined as cured if S. aureus was not isolated from the fresh or
      frozen culture from milk samples obtained following calving. The rate of cure by
      30 d after calving for systemic oxytetracycline (in combination with cephapirin
      treatment) was 29.4% for infected quarters and 29.4% for infected cows, compared
      with 27.5 and 25.0%, respectively, for the cephapirin treatment only. Results
      including the culture at 60 d after calving were 21.2 and 22.5%, respectively,
      for combination therapy and cephapirin therapy only. Systemic oxytetracycline, in
      combination with intramammary dry cow treatment, did not improve the rate of cure
      for S. aureus mastitis.

PMID- 7814712
TI  - Ecology of Staphylococcus aureus isolated from various sites on dairy farms.
AB  - The purposes of this study were to identify sources of Staphylococcus aureus on
      dairies and to determine whether S. aureus colonization of heifer body sites
      increases the risk of S. aureus IMI at parturition. In herds with high (> 10%) or
      low (< 3%) prevalence of S. aureus IMI, S. aureus was isolated from heifer teat
      skin, heifer external orifices, housing, feedstuffs, humans, nonbovine animals,
      air, and equipment. Additionally, in herds with high prevalence, S. aureus was
      isolated from bedding, insects, and water. The predominant sources of S. aureus
      for both groups were other IMI and heifer body sites. Heifers with prepartum
      lacteal secretions with S. aureus were at greater risk of S. aureus IMI at
      parturition than were prepartum heifers with lacteal secretions that were
      negative for S. aureus. Heifers with teat skin colonized by S. aureus were 3.34
      times more likely to have S. aureus IMI at parturition than were noncolonized
      heifers. Overall, 35% of 700 heifers were colonized with S. aureus on a body site
      at least once. Although colonizations of most body sites appeared to be
      transient, a few heifers were colonized on the same site for 1 yr. Persistently
      colonized heifers may represent the primary reservoirs of S. aureus for other
      heifers.

PMID- 7814713
TI  - The influence of sometribove dose and days in lactation on behavior of cows
      implanted with pelleted sometribove.
AB  - Data were from observations of behavior of 99 lactating Holstein cows during
      implantations with bST. Implantations were at 14-d intervals during 1 yr. Cows on
      one study received 0, 120, 240, or 360 mg; cows on a second study received 0,
      160, or 320 mg of bST per implantation. A checklist of behaviors was completed by
      the recorder and observer for each cow during implantation. Cows were also given
      an overall temperament score during each session. Lunging occurred in 49% of the
      sessions, but bellowing, kicking, and kneeling occurred least. More cows scored
      in the docile range than in the excited range. Cows habituated to head bobbing,
      back sagging, lunging, moving back in chute, flinching, head up, and bellowing,
      but not to shifting feet, kicking, shaking the head, head back, or ears back.

PMID- 7814714
TI  - Reproductive performance in high producing dairy cows treated with recombinant
      bovine somatotropin.
AB  - The reproductive performance of 156 cows treated with recombinant bST for two
      consecutive lactations was assessed as part of a target animal safety study
      conducted in the San Joaquin Valley of central California. Daily intramuscular
      administration of 17.2, 51.6, and 86 mg of bST per cow started at d 70 postpartum
      and ended at dry-off or 305 d postpartum. The AI did not begin until d 70
      postpartum. During the first lactation study, multiparous cows treated with bST
      had significantly decreased pregnancy rates, increased behavioral anestrus, and
      increased anestrus confirmed by palpation. Treated primiparous cows in first
      lactation had shorter mean days to first standing estrus. In the second lactation
      study, cows treated with bST had an increased rate of delayed uterine involution,
      cystic ovarian condition, behavioral anestrus, and anestrus confirmed by
      palpation. Progeny from the first lactation cows were evaluated for rates of
      growth, morbidity, mortality, and for reproductive performance; no difference was
      detected between the progeny from different groups.

PMID- 7814715
TI  - Pregnancy attrition associated with pregnancy testing by rectal palpation.
AB  - The objective of this study was to estimate the effect on calving risk of
      interval from AI date until scheduled date of pregnancy examination. First AI (n
      = 7105) from 65 dairy herds in the United States and Canada were followed for 294
      d to determine whether cows calved. Calving was modeled as a function of the
      number of days in the interval, herd, season, and breeding at PGF2 alpha-induced
      estrus by multivariate logistic regression. The main effects of herd and AI
      following PGF2 alpha-induced estrus were significantly associated with calving
      rate from first AI. The main effects of interval and season were not
      significantly associated with calving.

PMID- 7814716
TI  - Release of free fatty acids from raw or processed soybeans and subsequent effects
      on fiber digestibilities.
AB  - Two in vitro experiments were conducted to determine the rates of lipolysis and
      the extent of biohydrogenation of fat from raw or processed soybeans and to
      examine the subsequent effects on fiber digestibilities. In Experiment 1,
      substrates containing soy oil, raw soybeans, extruded soybeans, and soybeans
      roasted at 132, 146, or 163 degrees C were incubated with ruminal contents for 2,
      4, 6, 12, or 24 h; and release of FFA was measured. The FFA released from
      substrates containing soy oil, extruded soybeans, and raw or roasted soybeans
      reached maxima at incubations of 4, 6, and 12 h, respectively. As the roasting
      temperature increased from 132 to 163 degrees C, release of FFA decreased at
      incubations of 2, 12, and 24 h. Fatty acids in roasted soybeans were subjected to
      less biohydrogenation than those in raw or extruded soybeans, suggesting that FFA
      of roasted soybeans are partially protected from ruminal bacteria. In Experiment
      2, ground alfalfa hay was added to substrates used previously to determine the
      effect of release rate of FFA on ADF and NDF digestibilities. At all incubation
      times, the substrates containing soy oil and extruded soybeans had lower
      digestibilities, and those containing raw or roasted soybeans had higher
      digestibilities of NDF and ADF.

PMID- 7814718
TI  - Effects of cobalt on in vitro fiber digestion of forages and by-products
      containing fiber.
AB  - Cobalt glucoheptonate as a source of Co to enhance ruminal fiber digestion was
      evaluated in two in vitro digestibility experiments. In Experiment 1, Co
      supplementation (0, 5, and 10 ppm) of five substrates (leaf and stem fractions of
      alfalfa and orchardgrass hays and ground corn) was evaluated under two dietary
      conditions (ruminal fluid taken from steers fed alfalfa hay or a high concentrate
      diet) for 24 or 48 h of fermentation in a 3 x 5 x 2 x 2 factorial arrangement. In
      Experiment 2, four concentrations of Co (0, 10, 20, and 30 ppm) were added to
      five substrates (alfalfa hay, orchardgrass hay, corn cobs, recycled newsprint
      treated with HCl, and cellulose casings) and were incubated with ruminal fluid
      from steers fed alfalfa hay for 24 or 48 h of fermentation in a 4 x 5 x 2
      factorial arrangement. No interactions among treatments were observed for
      digestibilities of DM, OM, or NDF in both experiments or for VFA concentrations
      in Experiment 1. Supplementation with Co did not increase digestibilities of DM,
      OM, or NDF in either experiment or concentrations of VFA in Experiment 1. In
      Experiment 1, in vitro digestibilities of DM, OM, and NDF were higher for
      inoculum from steers fed alfalfa versus concentrate. In Experiment 2,
      digestibilities of DM, OM, and NDF were highest for alfalfa hay and lowest for
      recycled newsprint treated with HCl. Cobalt concentrations that were above
      minimum requirements did not improve digestion of DM, OM, or fiber.

PMID- 7814717
TI  - Supplemental dietary fat and ruminally protected amino acids for lactating Jersey
      cows.
AB  - Eight Jersey cows receiving a 50:50 ratio of forage to concentrate on a DM basis
      were used in a replicated 4 x 4 Latin square design to determine the effects of
      added fat (3.4% of dietary DM) and ruminally protected AA (8 g of Met and 24 g of
      Lys daily) on yield and composition of milk. Treatments were 1) basal control, 2)
      added fat, 3) added AA, and 4) fat plus AA. Compared with no added fat, fat
      supplementation increased 4% FCM yield (24.7 vs. 23.0 kg/d) and milk fat yield
      (1.05 vs. .97 kg), depressed milk protein content (3.58 vs. 3.74%), and altered
      fatty acid composition of milk. Blood triglyceride and NEFA were elevated (34.4
      vs. 29.5 mg/dl and 175.1 vs. 143.7 microeq/L, respectively) by added fat.
      Supplementation with AA elevated blood Lys, Met, and urea N without increasing
      milk protein yield. Increase in blood NEFA was further augmented by fat plus AA
      supplementation, but no changes in concentrations of Lys or Met in blood were
      found. Addition of AA did not alleviate the depression of milk protein content
      when supplemental fat was added to the diet for Jersey cows.

PMID- 7814719
TI  - Optimal breeding strategies for calving ease.
AB  - Calving ease is of economic importance in dairy cattle and should be considered
      in breeding programs. Economic values of direct and maternal calving ease were
      derived based on cost-benefit analysis and gene flow methodology. Marginal
      returns from dystocia reduction in primiparous dams were -$43 per phenotypic
      standard deviation compared with $300 for production. For an average mate,
      numbers of discounted expressions for sires to breed replacements were .58, .44,
      and .63 for direct and maternal calving ease and production. Discounted
      expressions for direct calving ease were higher when sires were mated to
      primiparous versus multiparous dams. Three alternative breeding strategies were
      compared: 1) separate selection of sires as mates of primiparous and multiparous
      cows, based on their respective optimal indexes for direct and maternal calving
      ease, 2) selection based on the optimal index for an average mate, and 3)
      selection on direct calving ease only. Strategies 2 and 3 allowed for assortative
      mating of sires with favorable direct calving ease to primiparous females
      subsequent to selection. Strategy 2 resulted in maximal economic response.
      Optimal standardized index weights under Canadian circumstances were
      approximately 100:9:7 for production:direct calving ease:maternal calving ease.
      Inclusion of calving ease traits had a minor effect (< .5%) on selection
      responses and efficiency but would provide proper guidelines to producers.
      Greatest benefits of genetic evaluations for calving ease were obtained through
      assortative mating.

PMID- 7814720
TI  - Alberta dairy farm survey response.
AB  - All dairy producers in the Canadian province of Alberta were mailed a
      questionnaire to determine current management practices and production. This
      survey was undertaken to develop and to plan extension programs based on current
      dairy producer needs. Of the producers contacted, 802 (57%) responded to the
      survey questionnaire. The results indicated that the mean herd size was 67 cows,
      and mean daily milk production was 21.9 kg/d per cow. More than 60% of the
      producers reported that the majority of their calf losses occurred at birth, and
      another 15.6% stated that losses occurred within the 1st wk. Less than one-third
      of the cooperators individually penned calves to prevent contact among calves
      prior to weaning. Approximately 31% of the cows in the herds surveyed required
      two or more breedings, partially because of inadequate estrus detection; only
      50.3% of the respondents had daily scheduled detection times. The most frequent
      health concerns perceived by the producers were mastitis, foot problems, and
      silent estrus. Educational and extension programs should focus on specific areas,
      such as newborn calf management and reproductive management, to improve the
      efficiency and profitability of dairy production in Alberta.

PMID- 7814721
TI  - Production responses of cows to recombinantly derived bovine somatotropin and to
      frequency of milking.
AB  - To determine whether bST additively increases milk production in cows milked at
      different frequencies per day, 118 Holstein primiparous and multiparous cows were
      milked two or three times daily beginning at parturition and received either 14
      mg of bST or no injection beginning at d 75 of lactation. Increased milking
      frequency from two to three times daily increased 3.5% FCM in multiparous (4.7
      kg/d) and primiparous (4.1 kg/d) cows over 305 d. Injection of bST increased FCM
      4.3 kg/d in multiparous cows and 5.0 kg/d in primiparous cows over 230 d.
      Increased milking frequency from two to three times daily reduced milk fat and
      protein percentages in milk, but bST generally did not affect these percentages.
      Injection of bST prevented increases in body condition score as lactation
      advanced, but increasing milking frequency from two to three times daily did not.
      In general, bST and increased milking frequency additively increased FCM in
      multiparous and primiparous cows.

PMID- 7814722
TI  - Galctopoietic effects of a (1-30)NH2 analog of growth hormone-releasing factor in
      dairy cows.
AB  - Two experiments were conducted to determine the galactopoietic effects of an
      analog of growth hormone-releasing factor. Specific replacements were made in the
      AA sequence of growth hormone-releasing factor to produce a growth hormone
      releasing factor analog with enhanced stability in vivo. In Experiment 1, 24
      Holstein cows were infused i.v. with 0, .33, 1, or 3 mg/d of growth hormone
      releasing factor analog for 20 d. Infusion of the analog increased mean serum
      concentrations of somatotropin, IGF-I, and NEFA. The analog also increased milk
      yield as much as 44% relative to that of controls. In Experiment 2, 24 Holstein
      cows were infused i.v. with 0, .11, .33, or 1 mg/d of analog for 60 d. Infusion
      of analog increased serum concentrations of somatotropin, IGF-I, and NEFA in a
      dose-dependent manner. At 1 mg/d, the analog increased SCM yield 28% throughout
      the infusion period relative to the 0 mg/d controls. In summary, a growth hormone
      releasing factor analog increased milk yield and serum concentrations of
      somatotropin and IGF-I. Furthermore, this galactopoietic activity was mediated
      through the somatotropic axis.

PMID- 7814723
TI  - Effect of naturally occurring coagulase-negative staphylococcal infections on
      experimental challenge with major mastitis pathogens.
AB  - The influence of pre-existing Staphylococcus sp. IMI on development of new IMI
      after experimental challenge with Staphylococcus aureus and Streptococcus
      agalactiae was studied. The IMI data were analyzed from five trials in which
      quarters were challenged with major pathogens incident to studies of teat dip
      efficacy. Prior to each trial, quarter IMI status was determined, and new IMI
      were enumerated during challenge. Percentage of new Staph. aureus IMI in
      uninfected quarters was 3-fold that of quarters already infected with
      Staphylococcus sp. Of quarters that were initially uninfected, 13.23% acquired
      new Staph. aureus IMI, and 4.49% of quarters infected with Staphylococcus sp.
      became infected. Conversely, the percentage of new Strep. agalactiae IMI in
      quarters infected with Staphylococcus sp. was 1.5-fold that of uninfected
      quarters (8.38 vs. 5.52%). The percentage of clinical Staph. aureus IMI in
      uninfected quarters was higher than for quarters infected with Staphylococcus
      sp., but percentages of clinical Strep. agalactiae IMI were similar among IMI
      statuses. Geometric mean SCC prior to challenge were 87 x 10(3) for uninfected
      quarters and 260 x 10(3)/ml for quarters infected with Staphylococcus sp.
      Quarters infected with Staphylococcus sp. were less susceptible to Staph. aureus
      IMI, but more susceptible to Strep. agalactiae IMI.

PMID- 7814724
TI  - Protein intake and development of ovarian follicles and embryos of superovulated
      nonlactating dairy cows.
AB  - Nonlactating Holstein cows (n = 12) were assigned randomly to one of two diets
      (approximately 30% concentrate) in a crossover design. Urea and soybean meal were
      used to increase CP content of diet from 12.3 to 27.4%. Mean concentrations of
      plasma urea were 9.8 and 21.3 mg/dl for respective diets. After 35 d on diets,
      cows were brought to a synchronized estrus (progestin implant plus PGF2 alpha
      injection). From d 10.5 to 14.5 following estrus, cows received i.m. injections
      of decreasing doses of FSH to initiate superovulation. On d 3 of FSH treatment,
      PGF2 alpha was injected with FSH. Cows were bred twice by AI when detected in
      estrus. Embryos were collected nonsurgically 6.5 d after breeding, and quality
      was assessed using visual, microscopic, and staining techniques. Development of
      follicles throughout this period was monitored using ultrasonography. Using
      ultrasonography, no differences were detected in the number or percentages of
      preovulatory, anovulatory, and ovulatory follicles induced during superovulation.
      Number of recovered embryos averaged eight per cow. Numbers and percentages of
      normal embryos, abnormal or retarded embryos, and unfertilized ova were similar
      between diets, as were the numbers and percentages of transferable and
      nontransferable embryos. Excess intake of CP failed to affect the growth or
      number of ovarian follicles and health and number of embryos of energy adequate,
      nonlactating dairy cows.

PMID- 7814726
TI  - Effect of hormonal treatment on fertility in dairy cows with dystocia or retained
      fetal membranes at parturition.
AB  - Holstein cows (n = 445) that had experienced dystocia, retained fetal membrane,
      or both at parturition were used to determine the effects of GnRH, PGF2 alpha, or
      both on various reproductive measurements. Cows affected with these conditions
      were assigned randomly to each of four treatment groups. One group of cows was
      untreated, and three groups received GnRH once at 12 d postpartum, or GnRH at 12
      plus PGF2 alpha at 26 d postpartum, or PGF2 alpha given at 12 and 26 d
      postpartum. Another group of 191 cows that calved normally were untreated.
      Conception rate after first AI was higher for cows treated with PGF2 alpha at 12
      and 26 d postpartum. Cows affected with dystocia, retained fetal membranes, or
      both and treated early postparum with GnRH alone or followed 14 d later with PGF2
      alpha did not have improved reproductive performance. Cows calving during the
      summer months of June through September experienced a reduction in the
      reproductive traits examined.

PMID- 7814727
TI  - Validation of indirect measures of body fat in lactating cows.
AB  - The objective of the study was to establish and compare equations that would
      estimate the body fat content of lactating dairy cows from different indirect
      techniques. The techniques used were body condition scoring, dilution of D2O in
      body water, and determination of mean fat cell size diameter of the subcutaneous,
      abdominal, and perirenal depots. Each technique was validated against direct
      determination of body fat content of the same lactating cows. To apply equations
      to high producing, lactating dairy cows, cows were from a herd producing more
      than 9500 kg of FCM/305 d, were lactating, and were in less than average body
      condition. Eight days prior to slaughter, a single injection of D2O was injected
      into the jugular vein, and body dilution was followed for 4 d. Cows were scored
      for body condition on the day of injection and weighed daily for the 4 d prior to
      slaughter. Samples of subcutaneous, perirenal, and omental adipose depots were
      taken, and adipocyte size and number were determined. Body fat was not predicted
      well by D2O space alone, but inclusion of BW did improve the prediction of body
      fat from this variable. The best equations were derived from use of BW with body
      condition score or subcutaneous fat cell diameter: observed body fat = -122.1 +
      .21 x BW + 36.0 x body condition score, and -195.6 + .290 x BW + .927 x
      subcutaneous fat cell diameter; standard errors of the estimate were 4.6 and 5.5
      kg, respectively. Equations using diameters of abdominal and perirenal fat cells
      gave similar relationships. Equations using all four predictors (live BW, fat
      cell diameter, condition score, and D2O space) were only slightly improved over
      these equations. Thus, use of body condition score, adipocyte diameter, and BW in
      laboratory and field conditions may help in the study and management of the use
      of body fat in lactating dairy cows.

PMID- 7814725
TI  - Interval from calving to conception in high producing dairy cows treated with
      recombinant bovine somatotropin.
AB  - Intervals from calving to conception in cows treated for two lactations with
      recombinant bST were ascertained using survival analysis methods. Daily
      intramuscular administration of placebo, 17.2, 51.6, or 86 mg of bST per cow
      started at d 70 postpartum and ended at culling or drying off. Breeding began at
      d 70 postpartum. Multiparous cows treated during the first lactation had
      significantly longer intervals from calving to conception. Cows treated during
      the previous lactation, but not during the second lactation, had significantly
      shorter intervals from calving to conception. Cox proportional hazards regression
      analysis was used with adjustment for the confounding effect of serum
      metabolites, milk production, energy balance, and body condition.

PMID- 7814728
TI  - Effects of alfalfa and orchardgrass on digestion by dairy cows.
AB  - The effects of alfalfa and orchardgrass diets of similar NDF content on ruminal
      digestion and digesta kinetics as measured using radiolabeled herbage were
      evaluated in Holstein cows. Two dry and two lactating cows, fitted with ruminal
      and duodenal cannulas, were fed 12 times daily at restricted and ad libitum
      intakes, respectively, in a crossover design. Diets were 65:35 and 55:45 hay:
      concentrate in DM for alfalfa and orchardgrass, respectively, with approximately
      19% CP and 42% NDF. The DMI by lactating cows was greater for the alfalfa diet
      than for the orchardgrass diet. Ruminal and apparent total tract digestibilities
      of NDF and ADF were less for cows consuming the alfalfa diet than for those on
      the orchardgrass diet. Particle size of ruminal digesta, based on specific
      activity from a ruminal pulse-dose of 14C-labeled alfalfa or orchardgrass, did
      not decrease consistently with time and was greater than fecal particle size,
      suggesting selective retention of large digesta particles before passage. Ruminal
      and total tract fractional passage rates of indigestible NDF, based on 14C
      labeled forage, did not differ as a result of forage or lactation stage, but NDF
      gut fill was greater in lactating than in dry cows, indicating that changes in
      gut fill were related more to differences in intake than to passage rate.

PMID- 7814729
TI  - Nonstructural carbohydrate and undegradable protein sources in the diet: growth
      responses of dairy heifers.
AB  - Thirty-five 3-mo-old 150-kg Holstein heifers were fed diets containing two
      nonstructural carbohydrate sources (corn or barley) with two quantities of
      undegradable protein (soybean meal or extruded soybean meal) for 9 wk in a 2 x 2
      factorial arrangement to evaluate NRC guidelines that the diet contain increased
      quantities of undegraded intake protein. Total mixed diets fed for ad libitum
      intake contained approximately 17.4% CP, consisting of 16.7% corn silage (DM
      basis), 33.3% chopped alfalfa hay, and 50% concentrate mix. Average daily gains
      were greater for heifers fed extruded soybean meal, but response was greater when
      heifers were fed barley-extruded soybean meal (1.12, 1.13, 1.05, and 1.23 kg/d
      for corn-soybean meal, corn-extruded soybean meal, barley-soybean meal, and
      barley-extruded soybean meal, respectively) than diets of barley-soybean meal.
      Extruded soybean meal increased DMI (5.9, 6.1, 5.2, and 6.7 kg/d), but DMI were
      similar when diets based on corn or barley were fed. Diets with greater
      concentrations of undegraded intake protein fed to dairy heifers resulted in
      greater DMI and average daily gains, but responses were greater when heifers were
      fed diets based on barley rather than corn. These results suggest that current
      NRC recommendations for undegraded intake protein fed to 3- to 6-mo-old dairy
      heifers are too high; diets containing 35 to 40% undegraded intake protein should
      be sufficient.

PMID- 7814730
TI  - Evaluation of a new high protein variety of soybeans as a source of protein and
      energy for dairy cows.
AB  - Twenty Holstein cows in midlactation were used in a Latin square design to
      evaluate the nutritional quality of a high protein soybean (CP 45%) fed raw or
      roasted. Treatments were 1) control (soybean meal); 2) conventional soybean
      (Maple Isle), raw; 3) conventional soybean, roasted; 4) high protein soybean (AC
      Proteus), raw; and 5) high protein soybean, roasted. Diets were formulated to be
      isonitrogenous and consisted of approximately 10% whole crop barley silage, 15%
      corn silage, 19% alfalfa silage, 31% rolled barley, 17% cracked corn, and from
      6.5 to 8.6% of the appropriate protein source on a DM basis. Replacement of
      conventional soybean with the high protein soybean increased milk and milk
      component yields. All soybean treatments lowered milk protein percentages versus
      soybean meal although milk protein yield was only reduced for the raw Maple Isle
      soybean treatment. Milk fat percentage was reduced for the roasted AC Proteus
      soybean treatment versus soybean meal and both Maple Isle soybean treatments,
      although total milk fat yield did not differ among treatments. Heat treatment by
      roasting tended to affect total milk yield positively for both types of soybeans,
      but only the increase for Maple Isle was significant. Milk from cows fed full fat
      soybeans had more long-chain fatty acids than milk from cows fed soybean meal.
      Roasting the soybeans further increased the amounts of long-chain fatty acids.
      The new high protein soybean, AC Proteus, appears to be an excellent source of
      supplemental protein and energy for lactating dairy cows.

PMID- 7814731
TI  - Effects of feeding practices on milk fat concentration for dairy cows.
AB  - Thirty-seven dairy farms, using high producing (7500 kg/yr per cow on average)
      Montbeliarde cows that were fed hay-based rations, were included in a detailed
      survey involving the structure of the farm and the herd, the quality of forage,
      the feeding practices in winter and summer, and genetic characteristics of the
      cows (breeding values and herd effects). These data were used to analyze
      variation in milk fat concentration among farms, particularly variation linked to
      environmental factors, as assessed by the herd effect. When farms were ranked
      according to herd effect of fat concentration, farms with the highest herd
      effects fed concentrate to cows in rolled form, distributed forage before or with
      the concentrate, and provided hay in the trough in summer. The effects of such
      practices on digestive phenomena in the rumen are discussed. This study supported
      the use of herd effects to identify factors related to variation in dairy cow
      performance.

PMID- 7814732
TI  - The effect of dietary energy concentration on calf performance.
AB  - At three locations, 120 calves were fed a high fat milk replacer at 10% of birth
      weight from d 5 through 13. On d 14, calves were assigned randomly within sex and
      date of birth to a 2 x 2 factorial arrangement of treatments. Treatments were (on
      a DM basis) high fat milk replacer (21.6%) and high fat starter (7.3%), high fat
      milk replacer (21.6%) and low fat starter (3.7%), low fat milk replacer (15.6%)
      and high fat starter (7.3%), and low fat milk replacer (15.6%) and low fat
      starter (3.7%). Milk replacer was fed at 8% of birth weight/d from d 14 to 35 and
      at 4% of birth weight/d from d 36 to 42. High fat replacer depressed DMI before
      and after weaning. High fat starter depressed DMI after weaning. Before weaning,
      calves gained more BW when fed low fat replacer. Calves fed low fat starter
      gained more BW after weaning. On d 56, BW were highest for calves fed low fat
      replacer and starter and lowest for those fed high fat replacer and starter.
      Growth or health of calves was not improved by fat addition to the diet.

PMID- 7814733
TI  - Diurnal fluctuations in plasma ions and water intake of dairy cows as affected by
      lactation in warm weather.
AB  - The presumption that water, Na, K, and Cl homeostasis is affected by the
      initiation of lactation, especially in hot weather, was examined. The study was
      conducted using five Israel Holstein cows at 1 to 2 wk before parturition (period
      1) and at 2 wk (initiation of lactation) and 7 wk (established lactation)
      postpartum (periods 2 and 3, respectively). In period 1, most water intake was
      related to feed (in the absence of overt Na or osmotic stimuli). In contrast,
      during lactation, drinking was probably a combined response to feed-related and
      hypertonicity stimuli. Diurnal fluctuations in plasma ions, frequency of
      drinking, and volume ingested at each drinking increased postpartum. In period 2,
      plasma ion concentrations still were regulated around mean values, which was not
      the case in period 3, during which large diurnal variation in mean values
      occurred. The lowest values and highest variabilities were recorded in period 3
      at midday. With the transition from the dry period to lactation, plasma
      concentrations of Na and Cl were reduced and became more labile, but the
      relationships between them remained stable. Plasma K seemed to vary independently
      of the two other ions. The reduced homeostatic efficiency of plasma ions during
      early and established lactation in hot weather may have consisted of an
      accumulation of their deficiencies, enhanced excretion of K in sweat, and
      sequestration of Na and Cl in the rumen.

PMID- 7814734
TI  - Immunological parameters of periparturient Holstein cattle: genetic variation.
AB  - The genetic variability of blood neutrophil functions, lymphocyte blastogenic
      responses to mitogens, serum Ig concentrations, and serum complement and
      conglutinin activities was investigated from 35 d prepartum to 35 d postpartum
      for 137 Holstein cows. Periparturient cows experience an immunosuppression of
      various immunologic parameters at calving. Heritability estimates were obtained
      before, during, and after the episodes of immunosuppression. Significant genetic
      variability occurred in the periparturient changes for total number of
      neutrophils, neutrophil chemokinesis, assays of the neutrophil respiratory burst
      associated with phagocytosis (cytochrome c reduction, chemiluminescence, and
      iodination), serum concentrations of IgG1, IgG2, and IgM, and serum homolytic
      complement activity. This variability implies that immune profiles could be used
      for the selection of cattle with improved innate immune response without adverse
      effects on milk productivity. These results should be considered tentative,
      however, because the number of observations included in the data were limited.

PMID- 7814735
TI  - Transformation of measurements percentage of white coat color for Holsteins and
      estimation of heritability.
AB  - Percentage of white coat color was measured on registration certificates of 4293
      Holstein heifers on eight dairy farms in Florida. Measurements of white
      percentage were by visual evaluation on one side of the upper body (head, neck,
      and trunk) only and obtained in increments of 5%. Mean, median, mode, standard
      deviation, and skewness of white percentage were 25.6, 15, 0, 26.9, and 1.03.
      Distribution of white percentages showed lack of normality. Original data were
      transformed using an extension of the Box-Cox transformation to approach
      normality and to provide maximum likelihood estimators of the transformed
      parameters. Heritability estimates for percentages of white coat color were
      computed using derivative-free REML with an animal model. Estimates of
      heritability were .715 from untransformed data and .779 for transformed. Standard
      errors of estimates were slightly lower (.032 vs. .035) following transformation.
      Additional study to find an improved transformation procedure still seems
      warranted.

PMID- 7814736
TI  - Genetic parameters of test day measures for somatic cell count, milk yield, and
      protein percentage of milking ewes.
AB  - Records from monthly test days for milk yield, natural log-transformed SCC, and
      protein percentage of 10,171 records of 3832 Spanish Churra ewes in 24 herds were
      analyzed to estimate genetic parameters. Heritabilities and genetic and
      phenotypic correlations for test day records were estimated using multivariate
      REML with an animal model, accounting for the effects of litter size, test day
      within herd group, age at lambing, and month in milk. Heritabilities for test day
      records of milk, log SCC, and protein percentage were .34, .04, and .13,
      respectively. Genetic correlations of test day measures of SCC with milk yield
      and protein percentage were -.37 and .37, respectively; phenotypic correlations
      were -.05 and .19. Considered as a random effect, test day within herd accounted
      for 28 and 17% of the total variance of test day milk yield and test day SCC,
      respectively. The correlation between milk yield and SCC because of the test day
      within herd, the covariation factor, was estimated to be -.16. Results indicate a
      moderately high heritability for milk yield, a low heritability for SCC, and
      moderate, negative genetic relationships between measures of SCC in milk and milk
      yield.

PMID- 7814737
TI  - Removal of within-cow differences between morning and evening milk yields.
AB  - Methods were explored for removing within-cow differences between a.m. and p.m.
      milk yields to allow direct comparison of consecutive milk yields. Daily a.m. to
      p.m. ratios of milk yield were studied for 504 lactations of 310 Holstein cows.
      Ratios varied within lactations and among cows. When the incomplete gamma
      function was used to characterize lactation curves, 89% of the variation in
      individual milk yields was explained when an a.m.-p.m. term was included. The
      a.m. to p.m. ratios increased over the course of lactations. Within-cow
      adjustment factors for a.m.-p.m. milking, based on weighted and unweighted
      averages of previous a.m. to p.m. ratios, changed as lactation length increased.
      A weighted moving average technique, which weighted the last a.m. to p.m. ratio
      by .15, compared with .85 for previous ratios, was considered to be the optimal
      method of calculating a factor for removing a.m.-p.m. effects.

PMID- 7814738
TI  - Multiple-country comparison of dairy sires.
AB  - A multiple-trait sire model was described in which yields of daughters in
      different countries were considered to be different traits. Such a model required
      estimates of genetic correlations among sire genetic effects in different
      countries. Observations were average daughter yield deviations, which were yields
      adjusted for all fixed effects within a country and for mate and animal permanent
      environmental effects. The methodology was described through a small example.
      Methods for estimating genetic covariances between countries as well as the
      advantages and disadvantages of the multiple-country approach to international
      comparisons were discussed. The proposed method appears to be better
      theoretically than methods in which the genetic correlations among countries are
      assumed to be 1. The relationships of estimated transmitting abilities of sires
      from the multiple-country analysis with international conversion formulas were
      discussed.

PMID- 7814740
TI  - Principal descriptors of body condition score in Holstein cows.
AB  - The objective of this study was to assess objectively the ability of observers to
      assess body condition of dairy cows. Four observers independently assigned a body
      condition score (five-point scale, .25 increments) and described the appearance
      of seven body regions of 225 Holstein cows. Areas described were the thurl
      region, ischial and ileal tuberosities, ilio-sacral and ischio-coccygeal
      ligaments, transverse processes of the lumbar vertebrae, and spinous processes of
      the lumbar vertebrae. An absolute body condition score was designated for each
      cow based on the modal body condition score for all observers. If there was no
      modal body condition score, the mean score was used for the absolute body
      condition score. Statistical analysis of principal components was used to examine
      the relationship between body region description and absolute body condition
      score. Descriptions of body regions were highly correlated across all absolute
      body condition scores. Four principal component vectors explained 83.6% of the
      variation of the body region correlation matrix. The first principal latent
      vector accounted for 55% of the variation and was uniformly correlated with all
      body regions. Analysis of variance of first principal latent vector as the
      dependent variable and absolute body condition score as the class variable
      indicated that body condition could be separated into .25 units between 2.5 and
      4.0, inclusively. Below 2.5 and > 4.0, body condition could only be separated by
      .5 units. Distinct changes in specific body regions were associated with change
      in absolute body condition score. Observers agreed with the absolute score 58.1%
      of the time, deviating by .25 units 32.6% of the time. A body condition score can
      be given to a cow based on principal descriptors of specific body regions between
      2.5 and 4.0 by .25 units.

PMID- 7814739
TI  - Factors affecting calculation and use of conversion equations for genetic merit
      of dairy bulls.
AB  - Factors affecting calculation and use of conversion equations were reviewed.
      Methods of expressing reliability of converted evaluations were surveyed. Of 16
      countries responding, 6 did not calculate reliability for converted evaluations,
      5 accepted reliability from the exporting country, and 5 assumed genetic
      correlations of .6 to 1.0 with the US. Genetic correlations between the US and 8
      other countries were estimated and generally were > or = .9; estimated
      correlations between the US and Canada were 1.0. Estimated correlations averaged
      .93 for milk, .89 for fat, and .92 for protein yields. Correlation estimates were
      lowest for countries differing most from the US in management conditions
      (Australia, New Zealand) or trait definition (Germany), which suggests that
      correlation estimates < 1.0 indicate differences in trait measurement as well as
      differences in biological expression. Conversion equations were computed from
      data of US and Canadian Holstein bulls with and against the gene flow. Equations
      against the gene flow generally had regression coefficients and intercepts lower
      than those calculated with the gene flow. Lower regression coefficients were
      explained by selection on the dependent variable. Lower intercepts were
      attributed to preferential treatment of daughters from imported semen, which
      would lower intercepts for equations against the gene flow and inflate intercepts
      with the gene flow.

PMID- 7814741
TI  - Bacteriocins produced by Leuconostoc species.
AB  - Leuconostoc spp. are lactic acid bacteria that are commonly associated with foods
      and that are used as starter bacteria in some dairy fermentations. Lactic acid
      bacteria are inhibitory to other bacteria because of pH, organic acids, hydrogen
      peroxide, and other chemicals produced during their growth, including
      bacteriocins. Bacteriocin production by Leuconostoc spp. was first observed in
      the 1950s, but only since 1984, when antagonistic activity of Leuconostoc spp.
      was reported, have more extensive studies of bacteriocins produced by Leuconostoc
      spp. been conducted, including mesentericin Y105, produced by Leuconostoc
      mesenteroides spp. mesenteroides; leucocin A-UAL 187, produced by Leuconostoc
      gelidum; carnosin 44A, produced by Leuconostoc carnosum; and leuconocin S,
      produced by Leuconostoc paramesenteroides. Bacteriocins produced by leuconostocs
      may or may not be active against other lactic acid bacteria, but all include
      Listeria in their activity spectra. Mesentericin Y105 is reported to be
      exclusively active against Listeria spp. The amino acid sequences for leucocin A
      and mesentericin Y105 have been determined. Despite considerable differences in
      antibacterial spectra, only two amino acids differ between these bacteriocins.
      The prevalence of leuconostocs in many adventitious fermentations of food and the
      use of leuconostocs as starter bacteria in controlled fermentations make the
      bacteriocins produced by these bacteria of interest as possible food
      preservatives by addition of the bacteriocin or its producer organism to foods.

PMID- 7814742
TI  - Endocrine and neural control of estrus in dairy cows.
AB  - During proestrus, gonadotropins induce final follicular maturation, resulting in
      increased secretion of estradiol. Estradiol, in the relative absence of
      progesterone, acts on the hypothalamus to induce estrous behavior. The mean
      duration of estrus is 12 to 16 h and ranges from 3 to 28 h. The effects of
      estradiol appear to be "all or none". That is, once a threshold of estradiol is
      achieved, estrus is induced, and additional amounts of estradiol above threshold
      do not further enhance the estrous response (duration and intensity of estrus).
      Also, progesterone can block the estrus-inducing actions of estradiol. In
      addition, prior exposure to progesterone does not potentiate the estrus-inducing
      actions of estradiol except in the early postpartum period. In dairy cows, the
      first postpartum ovulation is often "silent". In other words, ovulation is not
      preceded by estrous behavior. High levels of estradiol during late gestation
      apparently induce a refractory state such that the brain cannot respond to the
      estrus-inducing actions of estradiol at the first postpartum ovulation.
      Progesterone can "reset" the brain, allowing it to respond to subsequent
      estradiol exposure. In the case of the postpartum cow, the corpus luteum formed
      after the first ovulation provides the progesterone that resets the brain. As a
      consequence, the second postpartum ovulation is preceded by estrous behavior.
      Finally, stress (or injection of ACTH) has been shown to delay, shorten, or
      inhibit completely the expression of estrus in the presence of estrus-inducing
      concentrations of estradiol.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7814743
TI  - The estrus detection problem: new concepts, technologies, and possibilities.
AB  - The single most important problem limiting high reproductive efficiency in the
      national dairy herd is poor detection of estrus. Failure to detect estrus or
      erroneous diagnosis of estrus results in an estimated annual loss of over $300
      million to the dairy industry in the US. New technologies for the solution of
      this problem must be more effective than visual observation and aids currently
      used to detect estrus. Ideally, technologies that provide the solution for
      detection problems should provide the following: continuous (24 h/d) surveillance
      of the cow, accurate and automatic identification of cows in estrus, operation
      for the productive lifetime of the cow, minimized labor requirements, and high
      accuracy in identifying the appropriate physiologic or behavioral events that
      correlate highly with ovulation. New approaches are aimed at providing automation
      of detection of estrus using electronic technology. Pedometry, implantable
      impedance sensors, and surface-applied and implantable pressure sensors are in
      various stages of development and use.

PMID- 7814744
TI  - Measuring efficiency and accuracy of detection of estrus.
AB  - The ability of management to detect estrus efficiently and accurately in cows and
      heifers profoundly influences reproductive performance and profitability of dairy
      herds. Routine estimates of efficiency and accuracy are important to monitor
      reproduction in a herd and to evaluate management in problem breeding herds.
      Detection efficiency is usually expressed as the percentage of possible estruses
      that were observed over a given time period. Eight methods are presented that
      approximate efficiency using estrus and insemination dates. Efficiency can be
      estimated from herd summary information using the equation recommended by the
      Dairy Reproduction Core Parameter Committee or using equations that calculate the
      breeding interval. Milk progesterone concentrations measured by on-farm tests can
      be used to approximate efficiency. Seven of the nine Dairy Record Processing
      Centers calculate an efficiency estimate. Accuracy of detection of estrus is the
      percentage of estruses observed that are true estruses. Inaccurate detection of
      estrus results in breeding of cows not in estrus, thus lowering conception rates.
      Detection accuracy should be evaluated for herds experiencing low conception
      rates. Comparison of interestrual intervals, results of uterine and ovarian
      palpation, and progesterone concentrations of cows perceived to be in estrus can
      be used to estimate the accuracy of detection of estrus.

PMID- 7814745
TI  - Evaluation of chemical and physical properties of feeds that affect protein
      metabolism in the rumen.
AB  - The goal of the NC-185 Cooperative Regional Research Project is to provide the
      information needed to improve the nutrition and feeding of dairy cattle, a major
      factor determining composition of milk and cost of milk yield. Emphasis is placed
      on understanding how energy and protein nutrition of lactating cows can be
      manipulated to increase the quantity and improve the profile of AA passing to the
      small intestine and to improve yield of milk and milk protein. To achieve this
      goal, one of the major objectives of this project has been to evaluate
      quantitatively the chemical and physical properties of protein and energy sources
      that determine AA availability to lactating cows. Reliable measurements of
      microbial protein synthesis and protein degradation in the rumen are critical in
      the evaluation process. Therefore, one of the ongoing areas of investigation of
      this research project has been to determine the most appropriate methods for
      estimating microbial protein synthesis and dietary protein degradation in the
      rumen. Other areas have been investigated, using continuous culture fermenters
      and ruminally and duodenally cannulated cows, including factors that alter
      microbial metabolism of N in the rumen and subsequently protein supply to the
      small intestine, such as sources of carbohydrate, protein, and fat and
      interrelationships of protein and carbohydrate. Findings of the NC-185
      Cooperative Regional Research Project Committee and other investigators are
      summarized in this review.

PMID- 7814747
TI  - Impact of metabolism by extragastrointestinal tissues on secretory rate of milk
      proteins.
AB  - This paper reviews the current state of knowledge about the postabsorptive
      utilization of AA. Data on the duodenal entry of AA and the projected output of
      these same AA as milk protein demonstrate significant losses. Within the
      essential AA, these losses range from 70% for Thr to 40% for Met and Lys. For
      Val, almost half of the loss is due to its use for nonsecretory purposes by the
      mammary gland; values decrease to 0% for other AA. The liver is the other major
      organ, apart from the portal-drained viscera, that is responsible for significant
      AA disposal. Interactions of Met metabolism with other methyl sources and
      gluconeogenic precursors that can alter the Met requirement also are discussed.
      Data on the transhepatic and transsplanchnic AA balance in lactating cows, and
      the coordinated use of these balances with duodenal flow and mammary balance, are
      needed. Further research also is needed into the functionality of use of AA for
      purposes other than milk protein synthesis to determine whether excess catabolism
      of AA occurs; assuming it does, more efforts are needed to identify regulation of
      AA disposal in the crucial tissues.

PMID- 7814746
TI  - Absorption and delivery of nutrients for milk protein synthesis by portal-drained
      viscera.
AB  - The predictability of diet effects on milk composition is limited by the lack of
      understanding of the metabolic transformations that absorbed nutrients undergo
      within the portal-drained viscera and liver of high yielding dairy cows. The mass
      of splanchnic tissues increases dramatically in early lactation, but little is
      known about the regulation of gut growth and adaptation in early lactation, and
      further research may provide strategies for optimizing gut adaptation. Glucose is
      critical for milk synthesis, but portal-drained visceral tissues normally use
      rather than absorb glucose on a net basis. Dietary starch of low ruminal
      digestibility increases postruminal starch digestion and decreases net use of
      glucose by portal-drained viscera slightly, but increases in glucose absorption
      by portal-drained viscera never account fully for increases in starch
      disappearance from the small intestine and occur at the expense of VFA
      absorption. For cows in positive energy balance, greater glucose availability
      increases tissue energy balance and glucose oxidation, but has little effect on
      milk or milk protein yield. Similarly, chronic increases in propionate absorption
      have little effect on milk or milk protein yield. In contrast, casein infusion
      into the small intestine consistently increases milk and milk protein yield, but
      the mechanisms responsible remain unclear. There are few data describing the
      absorption and metabolism of AA by splanchnic tissues of lactating dairy cows,
      but, as for glucose and VFA, utilization of many AA by portal-drained viscera is
      substantial. In addition, the contribution of peptides to AA absorption and
      transport is uncertain and must be clarified. Therefore, measurements of nutrient
      disappearance from the lumen of the gut cannot be equated with nutrient
      appearance in the portal vein. Data describing metabolism of nutrients by portal
      drained viscera and liver of high yielding dairy cows are needed to improve
      feeding standards.

PMID- 7814748
TI  - Metabolic relationships in the supply of nutrients for milk protein synthesis:
      integrative modeling.
AB  - The objective of research under the NC-185 regional project is to identify the
      critical chemical transformations in the rumen, digestive tract, gastrointestinal
      and splanchnic tissues, and adipose and mammary tissues that define patterns of
      nutrient utilization in lactating dairy cows. This objective includes research on
      differences in fermentation, digestion, absorption, and tissue utilization of
      nutrients in sufficiently different situations to permit estimation of parameters
      defining various nutrient interconversions. The regional project is utilizing
      dynamic, mechanistic models of metabolism as tools for integrative analyses of
      experimental data generated by the group. During the early phases of the project
      emphasized herein, primary emphasis was on development of models of adipose
      tissue, mammary gland, liver, rumen, and whole animal metabolism. Serious
      inadequacies exist in the detail and scope of knowledge of rates of chemical
      transformations across the wide range of milk yields and nutrient intakes found
      in production situations. Current knowledge, as described in the various
      equations and parameters in the models, is presented and discussed. Some
      characteristics of the current models are illustrated, and methods to utilize the
      models to identify important experiments are discussed. More cooperative efforts
      are necessary, including experimental designs that focus on quantification of
      relationships between input and output, physiological mechanisms that alter
      patterns of nutrient utilization in lactating dairy cows, and yield estimates of
      the parameters describing the pre- and postabsorptive uses of feed nutrients.

PMID- 7814749
TI  - The G.V. Black IADR Year of Oral Health Lecture.

PMID- 7814750
TI  - Axon reflex vasodilatation in cat dental pulp elicited by noxious stimulation of
      the gingiva.
AB  - Antidromic stimulation of sensory nerves has been shown to increase blood flow in
      the tissue they innervate. This study was designed to determine if antidromic
      vasomotor responses occur in feline dental pulp and if they are mediated by
      branched axons supplying both tooth pulp and gingiva. Dynamic changes in pulpal
      blood flow (PBF) elicited by electrical stimulation, pinching, heating, and
      capsaicin application to the gingivae were investigated in cat mandibular canine
      teeth by means of Laser Doppler Velocimetry. All inferior alveolar nerve bundles
      and the cervical sympathetic trunk had been previously sectioned to avoid the
      occurrence of brainstem reflexes, e.g., somato-autonomic vasomotor reflexes.
      Increases in PBF were observed in seven out of 12 cats when a restricted gingival
      area adjacent to the canine teeth was stimulated as described, but the increases
      were abolished after the sensitive gingival area was painted with lidocaine
      jelly, a surface anesthetic. These vasodilator responses, remarkably reduced
      following repeated application of 30 mM of capsaicin, are considered to be
      induced via antidromic activation of capsaicin-sensitive nociceptive nerve
      fibers, presumably by axon reflex mechanisms, suggesting that nerve terminals
      supplying the gingiva originate from parent axons which have collaterals that
      innervate the canine tooth pulp.

PMID- 7814751
TI  - The effect of nerve injury on the incidence and distribution of branched pulpal
      axons in the ferret.
AB  - In a previous electrophysiological study in ferrets, we demonstrated that some
      axons in the inferior alveolar nerve branch to supply the pulps of two teeth. We
      have now investigated the incidence and distribution of branched pulpal axons at
      various intervals after nerve injury and subsequent regeneration, to study the
      extent to which the innervation of the teeth returns to normal. In adult male
      ferrets under anesthesia, the left inferior alveolar nerve was either sectioned
      (31 animals) or crushed (10 animals). Following recovery periods of six weeks,
      three months, or one year after nerve section and three months after nerve crush,
      electrophysiological recordings were made by insertion of pairs of Ag/AgCl
      electrodes into cavities cut into left mandibular teeth. Electrical stimuli were
      applied to each tooth in turn, and averaged responses were recorded individually
      from the other teeth. Latency and amplitude of the action potentials were used to
      characterize responses from branched pulpal axons. For some branched units, the
      point of branching was established by determination of the site of the inferior
      alveolar nerve section which abolished the response. When compared with controls,
      the results indicated that, following short recovery periods after nerve section,
      there was an increase in the number of branched pulpal axons supplying non
      adjacent teeth, and this branching had occurred at the initial site of nerve
      injury. Following long recovery periods, there were fewer branched axons than at
      earlier stages of recovery, but this apparent remodeling had not selectively
      eliminated axons which branched at the injury site to supply widely separated
      targets. Nerve crush injury resulted in no increase in the incidence of branched
      pulpal axons, and branching at the injury site was rare.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7814753
TI  - Characterization of the human junctional epithelial cells directly attached to
      the tooth (DAT cells) in periodontal disease.
AB  - This study examined the directly attached cells (DAT cells) of the human
      junctional epithelium from teeth extracted for advanced periodontal disease. The
      monolayer nature of the DAT cells remaining on the tooth surface after extraction
      offers a unique opportunity to study their morphology and activity in situ. We
      collected DAT cells and examined them by transmission electron microscopy and by
      autoradiography of cells labeled with 3H-thymidine. Our morphological results
      suggest that degenerative changes associated with pocket formation affect
      individual cells rather than regions of the DAT cell population at one time. The
      epithelial attachment apparatus (EAA) appeared to be the most resistant structure
      persisting on the tooth surface during the degeneration of the individual DAT
      cells. The new technique developed for two-dimensional observation of the sheet
      of DAT cells labeled in situ on the tooth surface in culture showed that the
      attached cells, even in periodontal disease, exhibit proliferative ability,
      suggesting a regenerative role for the DAT cells.

PMID- 7814752
TI  - Physiological regulation of the secretion of histatins and statherins in human
      parotid saliva.
AB  - The small salivary phosphoproteins, histatins and statherins, have important
      functions in the oral cavity in terms of antimicrobial actions and regulation of
      calcium phosphate homeostasis. Neither the effects of various physiological
      stimuli on their secretion nor the nature of the efferent receptor involved in
      the stimulus-secretion coupling has been determined previously. These aspects are
      important for improved understanding of the secretory control of salivary
      proteins and may have implications regarding the effects of specific medications
      on salivary constituents and oral health. The effects of graded mechanical
      (chewing on short and long silicone tubings) and gustatory stimulation (0.5, 1.5,
      and 5.0% citric acid) on the secretion of histatins and statherins were studied
      in the presence and absence of adrenolytic agents (n = 10). In this model,
      secretory rates of both proteins increased with increases in flow rate, with 5.0%
      citric acid representing a particularly potent stimulus. Histatin and statherin
      secretory rates were significantly reduced by the beta 1-adrenolytic agent
      (histatins to 58 to 72% and statherins to 11 to 29% of that in corresponding
      control experiments), but not by the alpha 1-adrenolytic agent. Since the beta 1
      adrenergic receptors played an important role in the stimulus-secretion coupling
      of these proteins, protective salivary functions in the oral cavity may be
      compromised during beta 1-adrenolytic treatment.

PMID- 7814754
TI  - Fracture surface characterization of clinically failed all-ceramic crowns.
AB  - The goal of this study was to establish a protocol for the retrieval and
      fractographic analysis of failed restorations, and to compare the fracture
      surface features of clinically failed ceramic restorations and with those of
      controlled laboratory test specimens fabricated from the same materials. Ten
      fractured Dicor crowns and 12 fractured Cerestore crows were retrieved and
      analyzed. Optical microscopy of the failed crowns revealed that the critical
      segments of nine of the 10 (90%) Dicor crowns and nine of the 12 (75%) Cerestore
      crowns were acceptable for fractographic analysis. Twelve disks of each material
      were fabricated as controls and fractured by bi-axial flexure for analysis of the
      similarities and/or differences between the fractographic features of fractured
      clinical crowns and the disks. Each of the 10 Dicor crowns was observed to fail
      along the internal surface. For 78% of the Cerestore crowns, failure initiation
      occurred at the porcelain/core interface or inside the core material. Critical
      flaw sizes of the failed Dicor crowns ranged from 127 to 272 microns. Failure
      stresses of the Dicor crowns, estimated by fractographic techniques and fracture
      mechanics relationships, ranged from 65 to 94 MPa. Estimated failure stresses for
      two of the Cerestore crowns which had failure initiation sites in the porcelain
      layer were 15 and 68 MPa. It is concluded that the fracture initiation sites of
      dental ceramics are controlled primarily by the location and size of the critical
      flaw, and not by specimen thickness.

PMID- 7814755
TI  - System for the pH-dependent release of a dye in model dental restorations.
AB  - We are developing a system for detecting recurrent caries under dental
      restorations. The controlled release of dyes under conditions of likely
      demineralization will alert the dentist to potential secondary caries. Production
      of acidic species is a characteristic of caries activity; hence, the system uses
      pH-sensitive polymers to release markers when the pH at the cavity wall of the
      restored tooth is below 6.5. The objectives of this investigation were to test
      the hypotheses that (1) the proposed system can be designed to release detectable
      marker continuously for at least six months in a simulated carious environment,
      and (2) the transient pH changes in the oral cavity caused by simulated dietary
      intake will not induce premature marker release from the pH-sensitive polymer
      placed beneath restorations. Two types of dye-loaded microspheres based on
      styrene, vinylpyridine, and divinylbenzene were prepared and placed on the floor
      of model cavity preparations made from an acrylic rod. Each model cavity was
      restored with a hybrid dental composite, placed in a vial with 5 mL of sodium
      lactate/lactic-acid base buffer solution, and stored at 37 degrees C. Solutions
      of three different pH values were used: 2.86, 4.73, and 6.39. The dye release
      into storage media was monitored periodically with a UV/VIS spectrophotometer.
      Results showed that the duration could extend beyond six months for pH > 4.73,
      and that transient oral pH changes are not likely to result in premature dye
      release. The data indicate that it would take approximately 21 days for the
      acidic agent external to the restoration to initiate dye release from restored
      sites.

PMID- 7814756
TI  - Dye-enhanced ablation of enamel by pulsed lasers.
AB  - Laser removal of dental hard tissue has been proposed as a replacement for or
      augmented approach to the dental handpiece. The main limitation for widespread
      usage of lasers in dentistry has been inefficient ablation of dental hard tissue,
      accompanied by potential laser-induced damage to the surrounding tissue. The
      research focuses on a novel approach for enhancement of tissue ablation and
      confinement of laser interaction to a small tissue volume by controlled placement
      of an exogenous dye on the enamel surface. Studies were done with both pulsed
      alexandrite and pulsed Nd:YAG lasers, with indocyanine green and India ink,
      respectively, used as photo-absorbers. These dye-enhanced laser processes
      demonstrated the feasibility of this technique for cavity preparation. While
      control studies produced little or no appreciable crater, average preparation
      depth for the dye-enhanced ablation was from 1 to 1.5 mm, with a diameter of
      approximately 0.6 mm. Knoop hardness measurements show that, surrounding the
      crater, there is small annular region slightly softened by the laser action. SEM
      studies of the interior structure of the tooth did not show significant damage to
      the surrounding tissue. Temperature measurement studies indicated that the pulsed
      nature of the laser, combined with the photo-absorbing dye, effectively prevented
      significant temperature rise at the pulp. The remarkable effectiveness of this
      technique in creating cavity preparations and the absence of any notable
      collateral damage to the surrounding tissue suggest that dye-enhanced pulsed
      laser ablation could be used as an alternative to the dental handpiece in
      selected procedures.

PMID- 7814757
TI  - Heat-treatment-induced reduction in the apparent solubility of human dental
      enamel.
AB  - Holcomb and Young (1980) have shown a significant increase in human dental enamel
      (HE) structural order resulting from heat treatment in the temperature range of
      from 275 to 400 degrees C. Also, previous work in our laboratory had shown
      dramatic decreases in the initial dissolution rates (IDRs) of both carbonated
      apatite (CAP) heated at similar temperatures (from 300 to 500 degrees C) and HE
      exposed to CO2 laser irradiation for which calculated surface temperatures were
      in this same range. We hypothesize that thermal treatment shifts the apparent
      solubility distribution profile of HE toward lower apparent solubilities,
      paralleling the observed increased in crystal structural order and the decrease
      in IDRs. Powdered HE was heated in a furnace at temperatures ranging from 150 to
      500 degrees C for 24 hours. The apparent solubility distributions of both heated
      and unheated HE powders were measured by equilibration for 24 hours in a series
      of partially saturated solutions simulating various amounts of HE dissolved in a
      pH 4.5 dissolution medium. The apparent solubility distribution for the unheated
      HE showed a peak at KHAP [the ion activity product based on the Ca10(PO4)6(OH)2
      stoichiometry] of 10(121.0). Heat treatment shifted the apparent solubility
      distribution to lower solubilities. The peak KHAP values were approximately
      10(124.8) at 200 degrees C; approximately 10(127.8) at 300 degrees C; and
      approximately 10(-129.1) from 400 to 500 degrees C. This approximately 8 orders
      of magnitude decrease in KHAP for HE heated at from 400 to 500 degrees C
      correlates with the previously observed reduction in the IDR driving force for
      laser-treated HE experiencing a similar surface temperature.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7814758
TI  - Acid profiles and pH of carious dentin in active and arrested lesions.
AB  - Organic acids in caries lesions play important roles in initiation and progress
      of dental caries. We investigated relationships between clinical types of dentin
      caries and acid profile or pH in the lesions. Caries lesions in dentin from 76
      permanent teeth were classified into active, arrested, situated beneath a
      restoration, and unclassified types. The pH of carious dentin was distinctly
      lower than that of sound dentin (p < 0.001). Carious dentin with a high
      percentage of lactate had a lower pH than that with a high percentage of acetate
      and propionate (p < 0.001). Dentin from active lesions showed a mean pH of 4.9,
      and the dominant acid was lactate (mean percentage, 88.2). In contrast, carious
      dentin from arrested lesions showed a higher pH, 5.7, with acetate and propionate
      as the dominant acids (mean percentages of acetate and propionate, 64.0 and 18.2,
      respectively). The acid profile (mean percentages of acetate and propionate, 54.0
      and 27.7, respectively) and pH (mean 5.8) of carious dentin sampled from lesions
      beneath a restoration were similar to those of dentin from arrested lesions. This
      study showed a clear relationship between clinical classification of dentin
      caries and acid profile and pH, suggesting that both factors are important in
      dentin caries etiology.

PMID- 7814760
TI  - Comodulation masking release for single and multiple rates of envelope
      fluctuation.
AB  - Two experiments are presented that investigate the influence of envelope
      fluctuation rate upon the magnitude of comodulation masking release (CMR). In
      Experiment 1, thresholds were measured for a tonal signal centered in either one
      or five masker bands. The maskers were either narrow-band noises or 100%
      sinusoidally amplitude-modulated (SAM) tones. The five masker bands had either
      the same (coherent) or different (incoherent) envelopes. Envelope rate was varied
      by manipulating either the noise bandwidth (10-200 Hz) or the SAM rate (10-128
      Hz). The CMR values were largest for slow envelope rates. In Experiment 2,
      envelope coherence was simultaneously manipulated at two rates by amplitude
      modulating (10 Hz) narrow-band noises (100 Hz). The modulation depth was 100%,
      83%, or 50%. The CMR based on the coherence of the noise carriers was about 5 dB,
      regardless of the SAM coherence or the modulation depth. The CMR based on the SAM
      coherence decreased from about 19 to 2 dB as modulation depth decreased,
      regardless of the noise-carrier coherence. Thresholds were highest when the
      envelope fluctuations were incoherent at both rates and were lowest when the
      envelope fluctuations were coherent at both rates. These data suggest that the
      auditory system is able to make across-frequency envelope comparisons at both
      envelope rates simultaneously.

PMID- 7814759
TI  - Comminution of food with mandibular implant-retained overdentures.
AB  - When complete-denture wearers are treated with from four to six implants and
      mandibular implant-borne prostheses, masticatory performance improves. No
      significant improvement has been observed with two implants and implant-mucosa
      borne overdentures, suggesting that the masticatory performance of edentulous
      subjects depends on the degree of support for their mandibular prostheses by
      implants or alveolar mucosa. To verify this hypothesis, we studied, in a
      randomized clinical trial, the comminution of an artificial test food during
      mastication. The trial involved the provision of a new maxillary denture and
      either a new conventional mandibular denture, a mandibular overdenture retained
      by two permucosal cylindric implants through a single bar-clip attachment, or a
      mandibular overdenture retained by a transmandibular implant through five clips
      on a triple-bar construction with cantilever extensions. In comparison with the
      subjects wearing mandibular implant-retained overdentures, the subjects with
      conventional complete dentures needed between 1.5 and 3.6 times more chewing
      strokes to achieve an equivalent reduction in particle size. No differences in
      masticatory performance and efficiency were found between the subjects who had
      received two permucosal cylindric implants and those who had received a
      transmandibular implant. The results suggest that the increased retention and
      stability of the mandibular denture, rather than the degree of support by
      implants or alveolar mucosa, determine the wearer's ability to comminute food
      during mastication.

PMID- 7814761
TI  - Effect of component-relative-entropy on the discrimination of simultaneous tone
      complexes.
AB  - Results are reported from a number of experiments investigating the effects of
      stimulus uncertainty on the discrimination of simultaneous multitone complexes.
      With few exceptions the data were well described by a model in which average
      threshold for the detection of a change in one or more components varies with the
      components' relative entropy (CoRE) in the complex [R.A. Lutfi, J. Acoust. Soc.
      Am. 94, 748-758 (1993)]. In different experiments, thresholds for the detection
      of a change in target level were found to be linearly related to CoRE for
      manipulations in the number of targets, the number of context tones, and the
      relative degree of level perturbation on tones from trial to trial. The slopes of
      the functions did not change with measures taken at different points on the
      psychometric function, and in most cases were close to the theoretical value of b
      = -1.0, as predicted by strict application of the model. Also as predicted (but
      for the exception of one listener) increasing the level of the target beyond that
      of the context had little or no effect on threshold. A correlational analysis of
      the trial-by-trial data revealed a tendency of listeners to give negative weight
      to frequencies immediately above the target, and to adjust weights in response to
      changes in the relative degree of level perturbation. Though inconsistent with
      the basic premise of the model, the variation in weights was not so great as to
      materially affect the predictions for mean thresholds.

PMID- 7814762
TI  - A comparison of the effectiveness of across-channel cues available in
      comodulation masking release and profile analysis tasks.
AB  - These experiments were designed to explore the benefit to signal detection of
      different types of across-channel cues, both alone and in combination. Some
      conditions were similar to those used in profile analysis (PA), and some to those
      used in comodulation masking release (CMR). Others were designed specifically to
      eliminate, or render unreliable, a particular across-channel cue so that the
      benefit to performance from another cue could be assessed. Thresholds for
      detecting an increment in level of a sinusoid, or of the carrier of a
      sinusoidally amplitude modulated (SAM) sinusoid, were measured in the presence or
      absence of four sinusoids or SAM sinusoids (flankers), two centered above and two
      centered below the signal frequency. The flankers were always modulated with the
      same depth as the target component during nonsignal intervals. The flankers, when
      present, were either equal in level to the nonsignal target sinusoid, or were
      scrambled in level (different in level both from each other and from the target
      by an amount that varied randomly from one stimulus to the next). In some
      conditions the overall level of the stimuli was also varied randomly from one
      stimulus to the next. The results indicate that about 5-6 dB of benefit arises
      from the cue of a disparity in level across frequency (a PA-type cue), and about
      1-3 dB from the cue of a disparity in envelope modulation depth across frequency
      (a CMR-type cue). For some subjects, slightly less benefit occurred when the
      flankers were presented to the opposite ear as the signal, requiring across-ear
      comparisons. Scrambling the level of the flankers often impaired performance,
      especially when the overall level of the stimuli was fixed. This appears to
      reflect an across-channel interference effect.

PMID- 7814763
TI  - The effect of burst duration, interstimulus onset interval, and loudspeaker
      arrangement on auditory apparent motion in the free field.
AB  - The illusion of auditory apparent motion (AAM) was examined in order to determine
      the burst durations and interstimulus onset intervals (ISOIs) at which AAM is
      heard when spatial information regarding source location was varied. In the first
      experiment AAM was examined in the free field under monaural and binaural
      listening conditions. AAM was heard at the same burst duration-ISOI combinations
      for both listening conditions, but the location of the lead source could be
      determined only under binaural listening. In the second experiment AAM was
      measured with two and three sound sources. The number of sources did not affect
      the burst duration-ISOI combinations that produced AAM, but did affect the
      determination of the location of the lead source. In the third experiment AAM was
      tested when the sources were located in the median plane. The sources were
      located either at 0 degrees and 180 degrees azimuth, or both at 0 degrees
      azimuth, one in the horizontal plane and one 20 degrees above. The location of
      the speakers did not affect the timing requirements for the perception of AAM,
      only the timing requirements for the detection of the lead source. In the fourth
      experiment, AAM was measured when the vertical separation between the sources was
      either 2.5 degrees or 20 degrees. AAM was heard at both separations, even though
      2.5 degrees is less than the vertical MAA. In each of these experiments only
      burst duration and ISOI determined whether motion was heard. Localization cues
      were important only for the determination of the direction of motion.

PMID- 7814764
TI  - Auditory brainstem response (ABR) peak amplitude variability reflects individual
      differences in cochlear response times.
AB  - Previously, it was shown [Don et al., J. Acoust. Soc. Am. 94, 2135-2148 (1993)]
      that cochlear response times are gender specific and about 13% shorter in females
      than in males. It is also suggested that one of the possible reasons click-evoked
      auditory brainstem response (ABR) waveforms recorded from females are better
      defined and have larger amplitudes than those of males is due to a sex difference
      in cochlear response times leading to better synchronization of the cochlear
      output across the frequency regions. Variability in cochlear response times would
      also lead to variability in click evoked ABR amplitudes. The high-pass noise
      masking derived ABR technique was used to investigate the effect of normalizing
      the individual temporal variability at the neural and cochlear levels. This
      involved adjusting for differences in neural conduction time (I-V delay) by a
      compression or expansion of the derived ABR waveforms and by adjusting for
      differences in cochlear response times by a shift of the derived ABR waveforms. A
      summation of the compressed and shifted ABRs results in a normalized unmasked ABR
      waveform that can then be compared for amplitude variability with the unprocessed
      unmasked ABRs. Compensation for the neutral I-V variability had little effect
      while compensation for cochlear response times, particularly the delay between
      the 5.7- and 2.8-kHz regions, greatly affected the amplitude of wave V of the
      compounded ABR. This work provides a better understanding of the significant
      relationship between cochlear response times and variability of the ABR peak
      amplitudes.

PMID- 7814765
TI  - Mean-scatterer spacing estimates with spectral correlation.
AB  - An ultrasonic backscattered signal from material comprised of quasiperiodic
      scatterers exhibit redundancy over both its phase and magnitude spectra. This
      paper addresses the problem of estimating mean-scatterer spacing from the
      backscattered ultrasound signal using spectral redundancy characterized by the
      spectral autocorrelation (SAC) function. Mean-scatterer spacing estimates are
      compared for techniques that use the cepstrum and the SAC function. A -scan
      models consist of a collection of regular scatterers with Gamma distributed
      spacings embedded in diffuse scatterers with uniform distributed spacings. The
      model accounts for attenuation by convolving the frequency dependent scattering
      centers with a time-varying system response. Simulation results indicate that SAC
      based estimates converge more reliably over smaller amounts of data than cepstrum
      based estimates. A major reason for the performance advantage is the use of phase
      information by the SAC function, while the cepstrum uses a phaseless power
      spectral density that is directly affected by the system response and the
      presence of diffuse scattering (speckle). An example of estimating the mean
      scatterer spacing in liver tissue also is presented.

PMID- 7814766
TI  - Response of constrained and unconstrained bubbles to lithotripter shock wave
      pulses.
AB  - The Gilmore formulation for spherical bubble dynamics [F. R. Gilmore, The Growth
      or Collapse of a Spherical Bubble in a Viscous Compressible Liquid (California
      Institute of Technology, Pasadena, CA, 1952), Rep. No. 26-4] is used to
      investigate the response of air bubbles to a variety of lithotripter shock
      waveforms. A modification of the Gilmore model is proposed to account for partial
      constraint of the bubble expansion that can be caused by bubble coatings (such as
      in echo contrast agents) and by tissues or vessels surrounding bubbles in vivo.
      In the modified formulation, a viscoelastic membrane is assumed to exist at the
      bubble interface to include the possible effects of the nonlinear elasticity and
      strain rate dependent viscosity on the bubble response. The stress induced in the
      membrane is assumed to be an exponential function of the bubble radius, which
      tends to restrict the bubble expansion. The viscosity is assumed to increase with
      the strain rate. In the absence of the membrane, the maximum bubble wall pressure
      induced by a negative (tensile) pulse is much larger than that induced by a
      positive (compressive) pulse of the same pressure waveform and amplitude. This
      difference increases with decreasing initial bubble radius. The addition of the
      viscoelastic membrane significantly decreases the predicted maximum bubble
      pressure and the difference in response between the positive and negative pulses.
      The effect of the time delay between double pulses (positive followed by negative
      or negative followed by positive) is also investigated for unconstrained bubbles.

PMID- 7814767
TI  - Across-frequency interaction in lateralization of complex binaural stimuli.

PMID- 7814768
TI  - From personal health into community action: another step forward in peer health
      education.
AB  - Health education as a field is turning from its individualist roots in which
      behavior change is viewed as an isolated phenomenon that occurs within an
      individual to a new contextual framework in which behavior change occurs within a
      complex ecology of individuals interacting with and influenced by other people,
      cultural norms, access to healthcare, affiliation with community--the entire
      environment of a person's life. This article focuses on the "how to's" of
      translating this shift in the field of health education into a practical and
      replicable action step forward in peer health education. The author first
      examines four assumptions implicit in many current peer health education training
      and program delivery models. She then describes a training curriculum that helps
      reshape the philosophy and activity of peer health education programs from an
      individualist paradigm grounded in information to a community-oriented model
      grounded in service. This training model, entitled From Personal Health Into
      Community Action, is intentionally designed to facilitate students' understanding
      of the connections between their personal health and the health of the community.

PMID- 7814769
TI  - Understanding volunteer peer health educators' motivations: applying social
      learning theory.
AB  - We conducted focus group interviews with students who were current peer health
      educators at a mid-sized university to determine what factors motivate
      individuals to volunteer for a peer health education program. Specifically, we
      asked the participants questions designed to explore their life experiences,
      their expectations of the peer education program, and their motivations.
      Constructs from social learning theory were used to categorize and contribute to
      our understanding of the responses. Many participants specified experiences with
      family members or friends, such as alcoholism or other illnesses, that had
      influenced their decisions. Participants' expectation of the program varied
      greatly and did not indicate a strong link to the decision to volunteer. The peer
      health educators' motivations for volunteering were altruistic, such as wanting
      to help others; egotistic, such as wanting job training; or related to self
      efficacy beliefs, such as satisfying a personal need for health education. This
      study indicated that life experiences, a belief in the effectiveness of peer
      health education programs, and positive reinforcement to join influence the
      decision to volunteer. Implications for coordinating peer education programs are
      discussed.

PMID- 7814770
TI  - Protocols constructed around the nursing process. 1: Asthma.
AB  - The author provides a nursing process style protocol for dealing with acute
      attacks of bronchial asthma in adult patients. Diagnoses, laboratory work, tests,
      treatment plans, including interventions for nurses, nurse practitioners, and
      physicians, are outlined. In addition, possible complications of bronchial asthma
      are listed and suggestions for patient education are offered.

PMID- 7814771
TI  - Sex-Tac-Toe.
AB  - With sexually transmitted diseases (STDs) increasingly present in the nation's
      adolescent population, health educators need innovative strategies for addressing
      cognitive, affective, and behavioral issues related to sexuality. Learning in a
      game format offers students a safe and entertaining opportunity to explore
      sexuality issues and discuss their concerns in a non-threatening environment. Sex
      Tac-Toe, which is based on the traditional game of tick-tack-toe, is played by
      two teams that compete to earn three squares in a row by answering multiple
      choice, true-false, and short-answer questions dealing with such topics as STDs,
      AIDS, contraception, and how to talk about sexuality issues. The game has been
      used in a college setting by both health educators and trained peer educators in
      residence hall and campus programs. It can be easily adapted for younger groups
      by changing squares or questions to meet the developmental level of the audience.

PMID- 7814772
TI  - Substance use and abuse among college students: a review of recent literature.
AB  - This article reviews the research literature since 1980 on alcohol and other
      (illicit) drug use among college and university students. The discussion begins
      with a summary of survey findings on the nature and extent of alcohol and drug
      use, including prevalence and patterns of use and associated problems. This
      summary is followed by a discussion of the correlates of substance use and
      problems, including demographic characteristics, personality factors, year in
      college and grade point average, college residence, motivation, and attitudes.
      The most popular substance used by college students is alcohol, used by about 90%
      of students at least once a year. Heavy alcohol use is also prevalent, and is
      associated with serious, acute problems. Although alcohol use has decreased
      somewhat in recent years, much larger declines in use have been recorded for
      illicit drugs. The major proportion of research on substance use in this
      population has been devoted to alcohol; more information is needed on the
      prevalence, patterns, and correlates of illicit drug use. Suggestions for coping
      with problems of campus alcohol use/abuse are offered.

PMID- 7814773
TI  - Cell cycle progression, aging, and cell death.

PMID- 7814774
TI  - Expression of G protein alpha subunits in the aging cardiovascular system.
AB  - Alterations in responsiveness to stimulation of G protein-coupled receptors in
      the cardiovascular system have been noted during aging and may be due to changes
      in the G proteins. The levels of G protein alpha subunits and their mRNAs were
      examined in the aorta and heart of adult (6-month-old) and senescent (24-month
      old) Fischer 344 rats. Western blot analysis using anti-Gs alpha antiserum
      revealed 4 bands in the aorta (38, 42, 45, and 52 kD). The 42 kD band decreased
      significantly in 24-month-old rats, whereas the other bands did not change.
      Western blots using anti-Go alpha and anti-Gi alpha revealed single bands of 39
      kD and 41 kD respectively, which decreased significantly in the aortas from 24
      month-old rats. There were no significant changes in the levels of G alpha mRNAs
      in the aorta during aging. In the heart, anti-Gs alpha antiserum detected 3 bands
      (42, 45, and 52 kD) which did not change with age. Levels of Gi alpha (41 kD) and
      Go alpha (39 kD) also did not change with age in the heart. The mRNAs for Gi2
      alpha and Gi3 alpha were significantly increased in the heart, but there was no
      change in Go alpha or Gs alpha mRNAs. Reduced expression of Gi alpha may provide
      the molecular basis for alterations in receptor responsiveness in the aging
      vasculature. Altered expression of G protein alpha subunits does not appear to
      account for age-related alterations in cardiac function.

PMID- 7814775
TI  - No evidence for a general change in contractile responsiveness of the mesenteric
      artery with aging.
AB  - Rings of human mesenteric artery (1-3 mm diameter) suspended in Krebs solution
      were contracted (maximal contraction relative to KCl 80 mM = 100%) by the
      thromboxane mimetic U46619 (190 +/- 10%), noradrenaline (162 +/- 9%), angiotensin
      II (107 +/- 11%), and 5-hydroxytryptamine (5-HT) (96 +/- 10%). Reducing
      extracellular Ca2+ strongly inhibited the maximal contraction to angiotensin II
      and 5-HT and moderately inhibited the maximal contraction to noradrenaline, but
      had less effect on the maximal contraction to U46619 (contraction in Ca2+ 1.3
      microM was reduced to 24 +/- 5, 20 +/- 3, 38 +/- 4 and 52 +/- 4% respectively of
      the contraction in 2.5 mM Ca2+). Reducing extracellular Ca2+ lowered sensitivity
      to 5HT, angiotensin II, and U46619, but did not alter sensitivity to
      noradrenaline. The EC50 and maximal contraction for each of the 4 agonists did
      not change with patient age at 2.5 mM Ca2+ or in reduced extracellular Ca2+. It
      is concluded that aging does not affect the responsiveness of mesenteric arterial
      smooth muscle to physiological vasoconstrictors.

PMID- 7814776
TI  - Slowing of contractile properties in quail skeletal muscle with aging.
AB  - The effect of aging on muscle contractile function was examined in the anterior
      latissimus dorsi (ALD) muscle of Japanese quails aged 8 weeks (young adults), 26
      weeks, 60 weeks, or 90 weeks (old birds). In vitro contractile measures of the
      ALD were made at 25 degrees C (stimulus pulse = 0.1 ms). Twitch contraction time
      in 90-week-old muscles was significantly greater than 8 to 26-week-old muscles
      (150 +/- 8 ms vs 168 +/- 18 ms). Similarly, one-half relaxation time of the
      twitch was increased in the ALD from old birds (221 +/- 17 ms) relative to adult
      birds 8-26 weeks (173 +/- 11). Aging produced a greater fusing of twitches at
      stimulation frequencies of 5 and 10 Hz, and this resulted in a leftward shift of
      the force-frequency curve at these frequencies. Shortening velocity measured by
      the force-velocity method (Vmax) decreased from 2.6 +/- 0.2 muscle length/s
      (mL/s) to 1.19 +/- 0.02 mL/s in 8 and 90-week-old muscles, respectively. Maximal
      velocity of unloaded shortening as measured by the slack test decreased from 3.6
      +/- 0.7 mL/s to 2.4 mL/s in 8-week-old and 90-week-old muscles, respectively.
      Maximal tetanic force (60.6 +/- 3.1 mN) and specific force (11.3 +/- 0.3 N/cm2)
      were similar in young adult and old muscles. These data indicate that aging
      induces a slowing of both twitch contractile characteristics and shortening
      velocity in the ALD, without affecting maximal force capabilities.

PMID- 7814777
TI  - A comparison of ventilation components in young and elderly men during exercise.
AB  - To elucidate the influence of age on ventilation components during exercise, we
      investigated the change in fractional contribution of abdomen or thorax during
      exercise in 12 elderly (71.9 +/- 5.3, mean +/- SD years) and 12 young (25.0 +/-
      4.9 years) normal male subjects using respiratory-inductive plethysmography. At
      rest, abdominal/thoracic contribution was not different between elderly and
      young. During exercise, abdominal contribution to total ventilation was decreased
      in the young compared to that at rest (rest: 53.6 +/- 2.9% vs exercise: 50.4 +/-
      1.9-48.9 +/- 1.8%; p < .01), but significantly increased in the elderly (rest:
      53.9 +/- 1.8% vs exercise: 57.3 +/- 1.7-59.8 +/- 2.0%; p < .01). Only in the
      elderly, respiratory frequency was increased during exercise compared to that at
      rest (rest: 20.1 +/- 0.8 [/min] vs exercise; 25.6 +/- 1.5-27.8 +/- 1.6 [/min]; p
      < .05). The breathing pattern in the elderly during exercise was partly simulated
      in the young by reducing thoracic compliance using chest strapping. This study
      demonstrates the greater participation of diaphragmatic motion together with
      rapid shallow breathing during lower graded exercise in the elderly as compared
      with the young. This ventilatory pattern during exercise may result from a
      stiffening of the thorax with advancing age.

PMID- 7814778
TI  - Effects of aging and caloric restriction on extracellular matrix biosynthesis in
      a model of injury repair in rats.
AB  - This study was designed to investigate the effects of aging and caloric
      restriction on collagen deposition in a model of wound healing. Polyvinyl alcohol
      sponges were implanted in Fischer 344 rats aged 6, 10, or 24 months. Sponges were
      removed after 7, 10, or 14 days and analyzed for hydroxyproline content and for
      enzymatic crosslinks. Aging was associated with a decrease in collagen
      accumulation as well as a delay in reaching peak rates of collagen accumulation.
      Levels of enzymatic crosslinks were increased in granulation tissue from old
      animals relative to young animals. Caloric restriction (60% of ad libitum intake)
      maintained only during the 2-week experimental period did not affect collagen
      accumulation, but did result in decreased levels of the difunctional crosslink
      dihydroxylysinonor-leucine (DHLNL) in sponges implanted for 10 days, but not 14
      days. Caloric restriction initiated 4 months before sponges were implanted
      resulted in decreased collagen accumulation and decreases in DHLNL at all
      implantation times. These studies suggest that: (1) aging affects total collagen
      production as well as rate of collagen production in response to injury; (2)
      aging is not associated with impaired crosslinking in granulation tissue; (3)
      chronic caloric restriction is associated with decreased collagen production and
      decreased levels of DHLNL; (4) the adverse effects of chronic caloric restriction
      on wound healing may have a greater impact on wound healing in old animals.

PMID- 7814780
TI  - Maintenance requirements for dietary protein in 11- and 18-month-old male rats.
AB  - Body weight, lean body mass (total weight less body fat), carcass protein, and
      serum protein were examined as potential parameters by which to assess the effect
      of age on protein requirements for maintenance in male rats, aged 11 months and
      18 months, fed diets containing 1.53, 3.41, 4.98, 6.52, or 8.05% dietary protein,
      casein plus methionine, for a 5-week period. Body weight change was maintained in
      older animals at 6.52% dietary protein and in younger animals at 4.98% dietary
      protein. Older animals consuming the two diets highest in protein had a greater
      percent body fat and less percent body protein than younger animals. Significant
      effects of diet and the interaction of diet and age on serum protein were also
      observed. As dietary protein level increased, serum protein increased gradually
      in younger rats, but only between 3.41 and 4.98% dietary protein in older rats.
      Lean body mass and total carcass protein increased as dietary protein level
      increased, but there were no significant differences due to age or the
      interaction of diet and age. Changes in body weight indicate a greater protein
      requirement for 18-month-old rats compared with 11-month-old rats, although
      complicated by greater food intake and fat deposits in older animals. Measures of
      body protein indicate that age has some influence on protein needs for
      maintenance purposes.

PMID- 7814779
TI  - Temporal pattern of food intake not a factor in the retardation of aging
      processes by dietary restriction.
AB  - Long-term dietary restriction programs which retard aging processes in rodents
      usually involve meal eating rather than the nibbling pattern of food intake of ad
      libitum fed rodents. Thus, the possibility arises that the antiaging action may
      at least in part result from an altered temporal pattern of food intake. This
      possibility was investigated using male F344 rats maintained on the following
      dietary regimens: Group A rats fed ad libitum; Group B rats fed 60% the ad
      libitum intake in a single meal at 1500 h; Group B-2 rats fed 60% of the ad
      libitum intake in two meals (0700 h and 1500 h). The diurnal pattern of plasma
      corticosterone concentration differed among the groups as did that of the plasma
      glucose concentration. The median length of life and age of tenth percentile
      survivors were similar for Group B and B-2 rats and much greater than those for
      Group A rats. Both modes of dietary restriction influenced age-associated disease
      processes in a similar fashion. Thus, although the temporal pattern of food
      intake influenced circadian rhythms of food-restricted rats, it did not
      significantly affect the antiaging action.

PMID- 7814781
TI  - A malathion resistance gene associated with increased life span of the rusty
      grain beetle, Cryptolestes ferrugineus (Coleoptera: Cucujidae).
AB  - The life span of the rusty grain beetle, Cryptolestes ferrugineus, was determined
      at 30 degrees C, 75% relative humidity (RH) for virgin and mated adults of a
      malathion-resistant strain (BC6RR), a malathion-susceptible strain (SS), the F1
      progeny of a cross between resistant females and susceptible males (RS), and an
      outbred strain (GV). The BC6RR strain was derived from the SS strain by
      incorporating the malathion resistance gene into the susceptible genome with six
      backcrosses and recovery of heterozygous resistant F1 adults between crosses. The
      mean life span of virgin, malathion-resistant adults (BC6RR and RS) was 37 weeks;
      the mean life span of virgin, susceptible adults (SS and GV) was 32 weeks.
      Resistant virgin adults lived significantly longer (15-16%) than susceptible
      virgin adults, and mated resistant adults lived significantly longer (3-20%) than
      mated susceptible adults (p < .05). Since C. ferrugineus has a relatively long
      reproductive period and females with the longest life spans produce the most
      offspring, life span can be considered an important component of fitness in this
      insect. The malathion resistance gene did not reduce fitness, and this gene or
      genes closely linked to it may be responsible for increasing life span in C.
      ferrugineus.

PMID- 7814782
TI  - Predictors of the age-related increase in blood pressure in men and women.
AB  - BACKGROUND: The age-related increase in blood pressure frequently observed in men
      and women may be more related to deleterious alterations in physical fitness,
      body composition, and diet than to a true aging phenomenon. Our purposes were to:
      (a) characterize the relationship between age and blood pressure in normotensive
      men and women; (b) identify physiological predictors of the age-related increase
      in blood pressure; and (c) examine whether the relationship between age and blood
      pressure persists after controlling for differences in these predictor variables.
      METHODS: Three hundred and sixty four Caucasian men (17-80 yr) and 215 Caucasian
      women (18-81 yr) were characterized for supine resting blood pressure, peak
      oxygen consumption, body composition, body fat distribution, plasma insulin and
      glucose concentrations, and nutritional intake. RESULTS: In men, the relationship
      between age and mean arterial pressure (MAP) (r = .25, p < .01) was no longer
      significant (partial r = .07, p = .20; 0.03 mmHg increase per year) after four
      predictor variables of MAP (fat mass, sum of 9 skinfolds, alcohol intake, and
      supine heart rate) were statistically controlled. In women, the relationship
      between age and MAP (r = .44, p < .01) no longer existed in women younger than 62
      years of age (partial r = .06, p = .46; .04 mmHg increase per year) after three
      predictor variables of MAP (waist-to-thigh ratio, supine heart rate, and alcohol
      intake) were held constant, whereas in women older than 62 the relationship
      persisted (partial r = .37, p < .01; 0.9 mmHg increase per year). CONCLUSION: In
      healthy Caucasian men and women between 17-81 years of age: (a) The relationship
      between MAP and age was stronger in women than in men, primarily due to an
      accelerated increase in MAP in women older than 62 years of age; (b) the age
      related increase in MAP in men was primarily related to an increase in body
      fatness, whereas in women the distribution of fat was the primary factor; and (c)
      after the influence of the predictor variables of MAP were controlled, the
      relationship between MAP and age persisted in women beyond 62 years of age, but
      not in women younger than age 62 or in men of any age.

PMID- 7814783
TI  - Exercise reduces age-dependent decrease in platelet protein kinase C activity and
      translocation.
AB  - BACKGROUND: This study examined the effect of age and aerobic exercise performed
      on a regular basis on human platelet protein kinase C (PKC) activity and
      translocation. METHODS: Blood platelets were obtained from young (20-36 years)
      and older (61-78 years) healthy male human subjects. Platelets were incubated
      with PMA, 5-HT, or thrombin; PKC activities were measured in partially purified
      extracts of cytosolic and membranous fractions. RESULTS: Platelet PKC activities
      associated with both the membranes and the cytosol cellular fractions were
      significantly reduced in older nonexercisers. Redistribution of platelet PKC
      activity elicited by stimulating the cell surface receptors for 5-HT or thrombin
      or by direct PKC stimulation (PMA) was found to be reduced in the elderly
      subjects. Maintenance of aerobic fitness in the older group of exercisers
      partially prevented the age-associated decline in platelet PKC activity and in
      stimuli-induced enzyme redistribution. CONCLUSIONS: These results indicate that
      platelet PKC activity and its translocation may be biological markers of aging
      and that aerobic exercise may serve to slow the rate at which enzyme activation
      declines during senescence.

PMID- 7814784
TI  - Intermittent claudication and subsequent cardiovascular disease in the elderly.
AB  - BACKGROUND: This study reports the prevalence of intermittent claudication (IC)
      in ambulatory community-resident adults age 65 years or older, compares
      cardiovascular risk factors and comorbidity of persons with and without IC, and
      examines the independent association of IC in predicting all cause and
      cardiovascular mortality, myocardial infarction, stroke, and disability. METHODS:
      Data are from a pooled sample of 8996 older adults from the East Boston, New
      Haven, and Iowa sites of the Established Populations for Epidemiologic Studies of
      the Elderly, conducted between 1982 and 1988. RESULTS: 2.4% and 1.5% of men and
      women, respectively, reported IC. Persons with IC had significantly higher rates
      of diabetes and cardiovascular comorbidity than persons without IC, and they were
      more likely to smoke. Claudication predicted higher rates of mortality,
      myocardial infarction, stroke, and disability independent of associated
      cardiovascular conditions and risk factors. Among persons with a history of
      angina, myocardial infarction, and/or stroke, those who reported IC had a twofold
      greater risk of cardiovascular mortality. CONCLUSION: The study demonstrated that
      IC is an important predictor of mortality and cardiovascular morbidity in
      ambulatory older adults independent of associated coronary ischemia and
      cardiovascular disease risk factors. Results suggest that inclusion of a measure
      of IC improves the prediction of cardiovascular morbidity and mortality in older
      adults.

PMID- 7814785
TI  - Effects of age and hypertension on adrenoceptor-sensitivity evaluated with CD25
      and QT/QS2.
AB  - BACKGROUND: We studied the effects of age and hypertension on responses to
      chronotropic dose (CD25) and standing-induced changes in the ratio of electrical
      systole (QT) to electromechanical systole (QS2) in order to identify their role
      on beta adrenoceptor sensitivity and to verify the value of QT/QS2 ratio as a
      noninvasive parameter of beta-adrenoceptor sensitivity. METHODS: We enrolled 33
      normal subjects and 37 hypertensive patients (WHO stage I and II) (age range 21
      82 years). RESULTS: CD25 was significantly age-related in normotensive and
      hypertensive subjects, whereas standing-induced QT/QS2 changes were age-related
      in normotensive subjects only When we divided subjects into three age groups,
      beta-adrenoceptor sensitivity was found to be lower in hypertensives than
      normotensives in the two groups under age 60, but was not affected in those over
      age 60. This suggests that hypertension influences beta-adrenoceptor sensitivity
      in younger subjects, but not in elderly patients, whose beta-adrenoceptor
      sensitivity is already reduced. CONCLUSIONS: CD25 does not predict standing
      induced QT/QS2 ratio changes; therefore, during autonomic stimulation, QT/QS2
      ratio seems not to be significantly related to beta adrenergic sensitivity.

PMID- 7814786
TI  - The Activities-specific Balance Confidence (ABC) Scale.
AB  - BACKGROUND: This study provides a replication of the Falls Efficacy Scale (FES)
      and a head-to-head comparison with the Activities-specific Balance Confidence
      (ABC) Scale designed to include a wider continuum of activity difficulty and more
      detailed item descriptors. METHODS: Items for the newly developed 16-item ABC
      Scale were generated by 15 clinicians and 12 elderly outpatients. Psychometric
      testing involved 60 community seniors (aged 65-95) self-classified as either high
      or low in mobility confidence according to their perceived need for a walking aid
      and personal assistance to ambulate outdoors. RESULTS: Both the FES and ABC
      scales were found to be internally consistent and demonstrated good test-retest
      reliability, convergent and criterion validity. Scalogram analyses indicated a
      stronger cumulative scale in the case of the ABC and skewness in the distribution
      of FES scores. While both scales were able to discriminate between the two
      mobility groups, the ABC scale was a more efficient discriminator and yielded a
      wider range of responses. CONCLUSIONS: The present study provided additional
      psychometric support for the FES. However, the greater item responsiveness of the
      ABC scale makes it more suitable to detect loss of balancing confidence in more
      highly functioning seniors. Greater situation-specificity of items may also
      assist clinicians in targeting appropriate interventions.

PMID- 7814787
TI  - Case mix controlled service use and expenditures in the social/health maintenance
      organization demonstration.
AB  - BACKGROUND: The social health maintenance organization (S/HMO) demonstration was
      implemented, in part, to determine if the presumed integration of acute and
      chronic care in these plans could produce sufficient savings to allow plans to
      offer expanded and chronic care benefits without increased cost to the Medicare
      program. METHODS: S/HMO members and a sample of fee-for-service (FFS) recipients
      were tracked over three years to assess their utilization experience. Analyses
      controlled for case mix, using Grade of Membership procedures. RESULTS: In 1987,
      the last year of risk sharing, S/HMOs reported higher total expenditures than FFS
      in each health status class. For the "healthy," differences were largest for
      physician care. In other classes, differences in nonskilled nursing or home care
      use were noted. In 1988, the first year of full risk, Seniors Plus had equivalent
      or lower expenditures relative to FFS for all classes. Elderplan had lower
      expenditures in four of six classes and provided more service to the "frail" and
      the "acutely ill." SHP had higher expenditures in all classes because of higher
      hospital and nursing home expenditures. Medicare Plus II had higher expenditures
      in all classes, for physician, nonskilled nursing home, and home care
      expenditures. CONCLUSIONS: Overall plan losses and higher expenditures among a
      number of case mix groups suggest a need for refinement of S/HMO operations-
      especially in case management relationships to medical care and in the selection
      of "high risk" cases.

PMID- 7814788
TI  - Extended stimulated parotid and submandibular secretion in a healthy young and
      old population.
AB  - BACKGROUND: Previous morphological studies have shown that both the human parotid
      and submandibular glands display age-related reductions in the proportion of
      fluid secreting acinar cells. In contrast, short-term functional studies of fluid
      secretion do not show such a consistent disparity among different-aged persons.
      This study compared the ability of a population of healthy young and old
      individuals to secret saliva from the parotid and submandibular glands for an
      extended period of time under conditions of intense gustatory stimulation.
      METHODS: Saliva was collected over 30 minutes from 30 healthy, unmedicated
      individuals using 10% citric acid as a gustatory stimulus. Of the 30 subjects, 15
      were young (age range 27-40 years) and 15 were old (age range 60-97 years).
      Parotid salivary flow rates were determined every minute, and submandibular flow
      rates were determined at 2, 10, 20, and 30 minutes. A comparison was made between
      the slopes of the two groups. The slopes were derived from the average salivary
      flow rate at each time point. RESULTS: There was no difference in the ability of
      the parotid glands of young and old individuals to secrete saliva. In contrast,
      the submandibular glands of the elderly individuals did not show the same pattern
      of secretion when compared to their younger counterparts, who demonstrated
      increasing flow rates over the test period. CONCLUSIONS: The parotid glands of
      young and old persons are able to maintain high secretory ability under the
      stress of intense stimulation for an extended period of time. Conversely, the
      submandibular gland demonstrates an age-related, statistically significant
      difference in the pattern of fluid secretion with an intense gustatory stimulus.

PMID- 7814789
TI  - Cognitive decline in Alzheimer's disease: a longitudinal investigation of risk
      factors for accelerated decline.
AB  - BACKGROUND: --Although Alzheimer's disease (AD) is a progressive degenerative
      condition, there is great intra- and inter-individual variability in rates of
      cognitive decline. Thus far, little data exist to explain such variability.
      Studies that have attempted to explain it have often been based on cross
      sectional designs, small sample sizes, and clinical population data. They have
      also failed to correct for level of cognitive function, despite clinical evidence
      that rate of decline varies among patients with varying levels of cognitive
      ability. METHODS: This study presents longitudinal data on a community-based
      sample of 156 patients diagnosed with probable AD, followed annually for one to
      five years (average age at entry = 79, range 54-91 years). The effect of level of
      cognitive impairment (as measured by the MMSE and Mattis DRS), demographic
      characteristics (e.g., education and age), behavioral problems (e.g., agitation),
      and co-existent health problems (e.g., vascular disease) on rate of decline was
      investigated via multivariate regression analysis. RESULTS: Study results
      indicate that the average rate of decline in cognitive function, as measured by
      the MMSE and mDRS, becomes more rapid as the disease progresses. Higher
      education, younger age, and agitation at intake were also significantly related
      to increased rates of cognitive decline.

PMID- 7814790
TI  - Arterial closing pressure correlates with diastolic pseudohypertension in the
      elderly.
AB  - BACKGROUND: Pseudohypertension has frequently been reported in the elderly
      population, with the diastolic measurement being the most frequent source of
      error. There is no satisfactory noninvasive method of calculating the error in
      the blood pressure reading. We investigated the role of arterial closing pressure
      in the diagnosis of diastolic pseudohypertension. METHODS: Indirect and direct
      blood pressure were measured in 24 elderly patients. Brachial artery closure was
      visualized by ultrasound in all subjects. Arterial closing pressure (ACP) was
      recorded as zero if the vessel was seen to close spontaneously when it was
      isolated from central arterial pressure. If the vessel did not close
      spontaneously, a water cuff was applied externally over the artery and the
      additional pressure required to close it was recorded. RESULTS: Diastolic
      pseudohypertension was noted in 8 subjects. Spontaneous closure of the brachial
      artery occurred in the 16 without pseudohypertension; i.e., ACP = 0. Additional
      pressure of the water cuff (range: 30-158 mm Hg) was required to collapse the
      artery (ACP) in those with diastolic pseudohypertension. ACP correlated with the
      extent of diastolic pseudohypertension (range: 5-17 mm Hg); r = .85, p < .001).
      CONCLUSION: We propose that ACP may be used to diagnose the presence and extent
      of pseudohypertension.

PMID- 7814791
TI  - A controlled trial of exercise training in older coronary patients.
AB  - BACKGROUND: This study compared the effects of a formal exercise conditioning
      program of 3 and 12 months duration to spontaneous recovery in a population of
      older, post-coronary event patients. METHODS: Indices of peak exercise and
      submaximal exercise performance such as oxygen consumption, treadmill work
      capacity, minute ventilation, heart rate, and systolic blood pressure were
      assessed before and after conditioning in 60 post-myocardial infarction and post
      coronary bypass surgery patients (mean age 68 +/- 5 years) and compared to
      measures of fitness in a usual care control group (n = 23, mean age 68 +/- 5
      years). RESULTS: Maximal treadmill work capacity increased by 47% in the
      intervention group at 3 months compared to no improvement in the usual care
      control group. However, both groups increased peak oxygen consumption similarly
      at 3 and 12 months, increasing by 16% and 20% in the intervention group at 3 and
      12 months and by 7% and 14% in the control group (p = n.s.). Only the exercise
      training group manifested submaximal indices of conditioning such as a lower
      heart rate and minute ventilation at a standard workload. CONCLUSION: While
      spontaneous improvements in peak oxygen consumption are seen in older coronary
      patients in the months following a coronary event, a formal exercise training
      program results in significantly greater increases in peak exercise capacity and
      in peak and submaximal exercise efficiency.

PMID- 7814792
TI  - Brain dysfunction in fulminant hepatic failure.

PMID- 7814793
TI  - Cerebral blood flow autoregulation is absent in rats with thioacetamide-induced
      hepatic failure.
AB  - Cerebral blood flow normally remains constant within a wide range of mean
      arterial blood pressure values. In fulminant hepatic failure, however, it is not
      known whether autoregulation of cerebral blood flow is maintained. In the present
      study, cerebral blood flow autoregulation was investigated in rats 3 days after
      induction of fulminant hepatic failure. Wistar rats were given intraperitoneal
      thioacetamide or saline injections. The mean arterial blood pressure was varied
      by means of norepinephrine infusion or venesection, respectively. As mean
      arterial blood pressure declined, repeated cerebral blood flow measurements were
      performed by the intracarotid 113Xenon injection method. The relation between
      mean arterial blood pressure and cerebral blood flow was examined by statistical
      regression analysis, and the lower limit of autoregulation was determined in each
      rat. Cerebral blood flow baseline values were unaltered in liver failure compared
      to the control group (73 (36-92) vs. 79 (57-87) ml.100 g-1.min-1, median and
      range). Baseline mean arterial blood pressure was also similar in the two groups
      (90 (75-113) vs. 95 (70-112)). Mean arterial blood pressure varied between 40 (35
      50) and 110 (90-135) mmHg in the control rats and between 50 (45-68) and 110 (95
      126) mmHg in the rats with liver failure. A lower limit of autoregulation was
      identified in all control rats at a mean arterial blood pressure of 67 (55-78)
      mmHg. Below this limit, cerebral blood flow declined in parallel with mean
      arterial blood pressure. None of the rats with liver failure exhibited
      autoregulation, and cerebral blood flow changed in parallel with mean arterial
      blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7814794
TI  - Thalidomide as therapy for primary biliary cirrhosis: a double-blind placebo
      controlled pilot study.
AB  - Thalidomide has been reported to be effective in treating graft-versus-host
      disease, a condition with many clinical and pathological similarities to primary
      biliary cirrhosis. We performed a double-blind, placebo-controlled pilot study to
      assess the efficacy of thalidomide in 18 patients with biopsy-proven primary
      biliary cirrhosis (10 thalidomide, 8 placebo). Each patient was treated for 6
      months and had a liver biopsy before and after treatment. Side effects,
      particularly sedation and fatigue, were more common on thalidomide and two
      patients were withdrawn from this group. There were no improvements in liver
      function tests or in liver histology, assessed morphometrically. A number of
      patients treated with thalidomide reported an improvement in pruritus. This study
      suggests that thalidomide is unlikely to be effective in altering the natural
      history of primary biliary cirrhosis.

PMID- 7814796
TI  - Portal pressure after prophylactic sclerotherapy in patients with high-risk
      varices.
AB  - Portal hemodynamics and transhepatic portal venographic findings were studied
      before and after prophylactic sclerotherapy (mean duration = 40 +/- 14 days) in
      16 patients with high-risk esophageal varices. Portal pressure, evaluated by the
      portal venous pressure gradient, increased by a mean of 21% in eight patients
      (50%) and decreased by a mean of 20% in eight patients (50%) with no
      statistically significant change overall. The two groups were further analyzed
      separately to identify the mechanism of the change in portal pressure.
      Intrahepatic vascular resistance did not change significantly in either group.
      However, the prevalence of extravariceal portosystemic shunts was greater in
      patients with decreased portal pressure than in those with increased portal
      pressure (88% vs. 25%, p < 0.05). Further, the enlargement of extravariceal
      portosystemic shunts was more marked in patients with decreased portal pressure
      than in those with increased portal pressure (88% vs. 0%, p < 0.01). In addition,
      liver function, assessed by intrinsic clearance, was not modified in the two
      groups. We conclude that prophylactic sclerotherapy increases or decreases portal
      pressure without modifying liver function. Although the mechanism of these portal
      pressure changes is not clear, intrahepatic vascular resistance does not play an
      important role and the presence of extravariceal portosystemic shunts may prevent
      further increases in portal pressure.

PMID- 7814795
TI  - Immunolocalization of a fibronectin-binding proteoglycan (PG-P1) immunologically
      related to HSPG2/perlecan in normal and fibrotic human liver.
AB  - Immunolocalization of a fibronectin-binding proteoglycan (PG-P1) in relation to
      fibronectin, type IV collagen and laminin, in normal and fibrotic human liver was
      investigated by light and electron microscopy. HS-42, which is a monoclonal
      antibody to PG-P1 and is reported to recognize a heparan sulfate proteoglycan
      named HSPG2/perlecan, was used for this purpose. Light microscopy in the human
      liver with minimal changes revealed that PG-P1 was present along the hepatic
      sinusoids as well as fibronectin and type IV collagen, whereas laminin was only
      weakly detected. In portal areas, PG-P1 was only localized on basement membranes
      around bile duct systems and blood vessels, as well as laminin and type IV
      collagen, while fibronectin was scarcely detected in basement membranes. In the
      fibrotic liver, fibronectin was abundant in necrotic and/or newly fibrosing
      areas, while PG-P1 was absent in these regions. Using immunoelectron microscopy,
      PG-P1 was localized in the space of Disse in nearly normal livers and was only
      detected on basement membranes in portal tracts. In fibrotic livers, PG-P1 in the
      space of Disse occasionally showed a basement-membrane-like deposition in
      parallel with the increased light microscopical deposition of laminin in this
      area, suggesting the positive participation of PG-P1 in the sinusoidal
      capillarization. Most capillary and sinusoidal endothelial cells, and rarely bile
      epithelial cells revealed the reaction products of PG-P1 in their rough
      endoplasmic reticulum and small vesicles. Thus, it was suggested that these cell
      types are mainly, if not wholly, responsible for PG-P1 production.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7814797
TI  - Intracellular calcium concentration in vascular smooth muscle cells of rats with
      cirrhosis.
AB  - A decreased pressor response to endogenous vasoconstrictors, such as angiotensin
      II and vasopressin, is a characteristic finding in cirrhosis with ascites; this
      has been considered as partially responsible for the arteriolar vasodilation
      present in this disease. Previous investigations suggested that this abnormality
      is due to a post-receptor defect leading to altered intracellular Ca2+
      mobilization. To assess this hypothesis, vascular responsiveness to angiotensin
      II (3.10(-8) M) and intracellular Ca2+ concentration in basal conditions and
      following angiotensin II (1-100 nM) and vasopressin stimulation (100 nM) were
      measured in aortic rings and in primary cultured aortic vascular smooth muscle
      cells, respectively. The study was carried out in 43 control rats and 40 rats
      with CCl4-induced cirrhosis and ascites. Cells were grown to confluence on glass
      cover slips and then loaded with Fura-2, a fluorescent intracellular Ca2+
      indicator, for continuous monitoring of intracellular Ca2+ concentration. A
      decreased constrictor response to angiotensin II was detected in cirrhotic aortic
      rings in comparison to control rings (increase in tension: 31 +/- 5 vs 79 +/- 14
      mg, p < 0.005). No differences in intracellular Ca2+ concentration between
      cirrhotic and control cells were observed in basal conditions (104 +/- 6 and 100
      +/- 3 nM, respectively). Angiotensin II administration to cirrhotic vascular
      smooth muscle cells had a dose-dependent biphasic effect consisting of a rapid
      increase, followed by return to a sustained level significantly higher than the
      basal value. This response was identical to that observed in control vascular
      smooth muscle cells. Similar findings were obtained following vasopressin
      stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7814798
TI  - Serum levels of macrophage colony stimulating factor (M-CSF) in liver disease.
AB  - We investigated the serum level of macrophage colony stimulating factor in acute
      and chronic liver disease. Levels of macrophage colony stimulating factor (mean
      +/- SD, ng/ml) were significantly higher in acute hepatitis (5.67 +/- 1.01, p <
      0.01) and chronic active hepatitis (3.34 +/- 1.19, p < 0.01) than in healthy
      volunteers (1.90 +/- 0.25), asymptomatic hepatitis B virus carriers (1.98 +/-
      0.40), and chronic persistent hepatitis (2.34 +/- 0.43). Levels of macrophage
      colony stimulating factor showed a highly significant correlation with the serum
      alanine aminotransferase levels in acute hepatitis (p < 0.01, rs = 0.903) and in
      chronic active hepatis (p < 0.01, rs = 0.672). Levels of macrophage colony
      stimulating factor in patients with cirrhosis (cirrhosis; 3.11 +/- 0.93 and
      hepatocellular carcinoma; 3.30 +/- 0.74) were significantly higher than in
      patients with chronic persistent hepatitis although the alanine aminotransferase
      levels were not significantly different. In cirrhosis, levels of macrophage
      colony stimulating factor correlated positively with the serum alanine
      aminotransferase levels (p < 0.05), total bilirubin levels (p < 0.05), and
      indocyanine green clearance (p < 0.05). An immunohistochemical study showed an
      increased number of macrophage colony stimulating factor positive mononuclear
      cells in portal areas in acute hepatitis. Our findings suggest that; (a) the
      serum levels of macrophage colony stimulating factor represent ongoing
      hepatocellular necrosis in acute and chronic liver disease, (b) the source of the
      increase in the serum macrophage colony stimulating factor levels in hepatic
      inflammation may be, in part, its production by infiltrating mononuclear cells in
      the liver, and (c) cirrhosis also causes elevated serum levels of macrophage
      colony stimulating factor.

PMID- 7814799
TI  - Recurrence of hepatitis C following orthotopic liver transplantation: a
      polymerase chain reaction and histological study.
AB  - Hepatitis C virus was sought by nested polymerase chain reaction in the
      preoperative biopsy or the explanted liver of 100 consecutive adult patients
      undergoing orthotopic liver transplantation. In those found to be positive
      preoperatively, polymerase chain reaction was performed on subsequent biopsies.
      Of the 12 patients in whom HCV-RNA was identified in the liver by polymerase
      chain reaction preoperatively, viral recurrence was documented in ten of the 11
      with posttransplant liver tissues available for study. In the one exception,
      hepatitis C virus was undetectable in the liver graft despite repeated co
      amplification of albumin mRNA as an internal control, which may indicate viral
      clearance. In eight of the ten positive cases, HCV-RNA was also detectable in
      serum postoperatively, while HCV-RNA was undetectable in serum in both the cases
      in whom HCV-RNA was undetectable in tissue and in the patient who declined post
      transplant biopsy. Two of the 12 patients infected with hepatitis C virus
      preoperatively have died during the follow-up period from causes unrelated to
      hepatitis C virus infection. While biochemical liver function in seven of those
      remaining has been excellent, histological evidence of at least mild chronic
      active hepatitis has been present in all ten cases for whom long-term biopsies
      are available. Three cases have progressed to severe, symptomatic chronic active
      hepatitis within 2 years of transplantation. Recurrent hepatitis C is associated
      with progressive liver disease and appreciable morbidity in a significant
      proportion of patients.

PMID- 7814800
TI  - Regulation of interleukin-6 receptor expression in rat Kupffer cells: modulation
      by cytokines, dexamethasone and prostaglandin E2.
AB  - Interleukin-6 has a variety of biological effects, mainly on the immune system.
      The regulation of this signal at both the site of production and the site of
      action is necessary to maintain the organism's homeostasis. In the
      microenvironment of the hepatic sinusoids, Kupffer cells as resident macrophages
      are the most potent source of interleukin-6 during inflammation. This cytokine is
      an important signal to hepatocytes during the early stages of the acute-phase
      response, leading to the expression of several major plasma proteins. Kupffer
      cells were found to express interleukin-6 receptor constitutively. Interleukin-6
      decreased the level of interleukin-6 receptor mRNA, indicating an autocrine
      pathway by which Kupffer cells regulate their responsiveness to interleukin-6.
      Furthermore, lipopolysaccharide, tumor necrosis factor-alpha, interferon-gamma,
      interleukin-1 beta and phorbol ester induced interleukin-6 production and, at the
      same time, suppressed the level of interleukin-6 receptor mRNA. The existence of
      an autocrine loop in rat Kupffer cells may be physiologically relevant, as it
      would contribute to a regulated interleukin-6 signal chain in the liver. The anti
      inflammatory mediators dexamethasone or PGE2 and its second messenger, cyclic
      AMP, increased interleukin-6 receptor mRNA, whereas prostaglandin D2 or the Ca2+
      ionophore, A 23187, were without effect. The changes in interleukin-6 mRNA were
      paralleled by the number of interleukin-6 receptors present on Kupffer cells as
      detected by binding of 125I-interleukin-6. These results suggest the existence of
      control mechanisms involving several soluble mediators that help balance the
      level of interleukin-6-R mRNA in rat liver macrophages.

PMID- 7814801
TI  - Oleate uptake kinetics in the perfused rat liver are consistent with
      pseudofacilitation by albumin.
AB  - We measured uptake of a representative free fatty acid, oleate, by the single
      pass perfused rat liver at oleate:albumin molar ratios of 0.01 to 2:1. For each
      ratio, uptake was studied at albumin concentrations from 50 to 600 microM. When
      uptake velocity was plotted as a function of the albumin concentration, the data
      at each ratio exhibited a pseudosaturation pattern as previously observed in
      isolated cells (J Clin Invest 84: 1325). At a physiologic albumin concentration
      of 600 microM, a plot of uptake vs. unbound oleate concentrations was best fitted
      by the Michaelis-Menten equation (Vmax = 235 +/- 8.8 nmol.min-1.g.liver-1; Km =
      130 +/- 12 nM). As the albumin concentration was increased from 50 to 250 microM,
      the unbound oleate clearance, calculated by either the undistributed sinusoidal
      or venous equilibrium models, increased progressively, in violation of
      conventional pharmacokinetic theory, indicating an enhancing effect of albumin on
      ligand uptake at low albumin concentrations. In contrast, there was no
      significant difference between measures of unbound clearance at albumin
      concentrations of 350 and 600 microM. To explain this phenomenon, the clearance
      data were examined for evidence of facilitation (accelerated dissociation of
      ligand:albumin complexes) by the clearance ratio test ("square root rule"). All
      deviations from the predictions of conventional theory were entirely attributable
      to pseudofacilitation. No data required explanation by a true facilitation model.

PMID- 7814802
TI  - Ultrastructure of the intracellular membranous system of rat hepatocytes in
      intrahepatic cholestasis induced by phalloidin.
AB  - To investigate the effect of a thickened pericanalicular ectoplasm in
      tubulovesicular transport and biliary excretion, we examined the ultrastructure
      of the intracellular membranous system in rat hepatocytes with and without
      phalloidin treatment, by transmission electron microscopy and scanning electron
      microscopy combined with the Aldehyde prefix Osmium-Dimethyl Sulfoxide-Osmium
      method. Hepatocytes possessed elaborate networks of tubules around bile
      canaliculi, and some of them extended to the bile canaliculi in control rats.
      Vesicles were also present around the bile canaliculus. Treatment of rats with
      phalloidin produced a thick pericanalicular ectoplasm around the bile canaliculus
      visualized by transmission electron microscopy, and the density of vesicles (p <
      0.001) and tubules (p < 0.001) within 0.5 microns around the bile canaliculus
      significantly decreased in phalloidin-treated rats. The number of lysosomes in
      hepatocytes apparently increased in phalloidin-treated rats; however, they were
      rarely observed around the bile canaliculus. The Aldehyde prefix Osmium-Dimethyl
      Sulfoxide-Osmium method produced an organelle-free space around the bile
      canaliculus by removing the thick pericanalicular ectoplasm in scanning electron
      microscopic examination, and the thickened pericanalicular ectoplasm inhibited
      the approach of intracellular membranes to the canalicular membrane in the
      transmission electron microscopic examination. In some pathological cholestatic
      conditions, the thickened pericanalicular ectoplasm may inhibit not only bile
      canalicular contraction but also biliary excretion of substances, which is
      mediated by the tubulovesicular transport system.

PMID- 7814803
TI  - Inhibition of the increase of intrahepatic Ca2+ by diltiazem in rats with liver
      ischemia.
AB  - The effects of a continuous infusion of a calcium entry blocker, 1, 5
      benzothiazepine derivative (diltiazem), on ischemic liver cell damage were
      studied using quantitative 45Ca-autoradiographic and liquid scintillation
      techniques. The drug was administered to male Wistar rats as a continuous
      infusion for 3 h, beginning 30 min before ischemia. Autoradiographic studies
      showed that 45Ca accumulated in the liver lobuli after 1 h of liver ischemia and
      3 h of reperfusion, but the level of 45Ca accumulation was significantly lower in
      drug-treated rats than in untreated animals. In addition, liquid scintillation
      studies showed significant differences in the intrahepatic 45Ca contents. These
      results suggest that diltiazem may inhibit the rise of intracellular Ca2+ due to
      the flow of extracellular Ca2+ into the cytosol, and may protect the ischemic
      liver from damage.

PMID- 7814804
TI  - Ultrasound, hepatic lymph nodes and chronic active hepatitis.
AB  - Thirty-two consecutive patients with a histological diagnosis of chronic active
      hepatitis were examined with liver biopsy, laboratory tests and ultrasonography
      of the hepato-duodenal ligament to investigate the possible correlation between
      enlarged lymph nodes in the hepato-duodenal ligament and biochemical activity,
      histological activity and/or humoral immunoreactivity. We found a significant
      correlation between lymph-node size and serum alkaline phosphatase in the total
      material. In the hepatitis C-virus-associated group of patients a significant
      correlation between the size of the lymph nodes and gamma-glutamyl transpeptidase
      was found. In the autoimmune group there was a trend towards a negative
      correlation between lymph-node size and albumin.

PMID- 7814805
TI  - The use of granulocyte-macrophage colony-stimulating factor to enhance
      hematologic parameters of patients with cirrhosis and hypersplenism.
AB  - In patients with end-stage liver disease complicated with hypersplenism,
      neutropenia and thrombocytopenia are risk factors for systemic sepsis and
      spontaneous bleeding. Granulocyte-macrophage colony-stimulating factor is a
      naturally occurring cytokine that promotes proliferation and differentiation of
      granulocyte and monocyte progeny cells. In addition, it is reported to promote
      the proliferation of megakaryocytes. Its use as an intravenous infusion is
      Federal Drug Authority (USA) approved for the enhancement of myeloid recovery
      following autologous bone-marrow transplantation. The present study was initiated
      to determine whether granulocyte-macrophage colony-stimulating factor could be
      used to increase the white blood cell and platelet count in patients with
      cirrhosis and hypersplenism and to determine whether the more convenient
      subcutaneous route can be used with the same efficacy as the recommended
      intravenous route. Nine patients with cirrhosis and hypersplenism manifested by a
      reduced absolute neutrophil count (mean value of 1300 +/- 200/mm3) were studied.
      In eight patients, Indium white blood cell splenic sequestration scans were
      obtained before and after the administration of granulocyte-macrophage colony
      stimulating factor intravenous infusion or subcutaneously for 7 days. One patient
      had to discontinue the therapy due to a reaction to granulocyte-macrophage colony
      stimulating factor. Following intravenous infusion of granulocyte-macrophage
      colony-stimulating factor, the mean absolute neutrophil count increased to 2600
      +/- 1100/mm3. Following subcutaneous administration, the mean absolute neutrophil
      count increased to 4100 +/- 200/mm3. No significant change in platelet count
      occurred with either route of administration. Indium scans obtained before and
      after the treatment period revealed no significant difference in the splenic
      uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7814806
TI  - Exclusion in liver by polymerase chain reaction of hepatitis B and C viruses in
      acute liver failure attributed to sporadic non-A, non-B hepatitis.
AB  - Hepatitis B and C viruses have been implicated in a few cases of acute liver
      failure attributed to sporadic (community acquired) non-A, non-B hepatitis, but
      reports are conflicting. We determined whether hepatitis B virus and hepatitis C
      virus were detectable in prospectively stored hepatectomies from seven British
      patients grafted for acute liver failure attributed to sporadic non-A, non-B
      hepatitis. For hepatitis B virus, we used nested polymerase chain reaction with
      primers to the core and surface regions. For hepatitis C virus, we used one round
      of reverse transcription polymerase chain reaction with primers to the 5'
      untranslated region and Southern hybridization using an internal oligonucleotide
      probe as well as nested PCR for the E1 region. Positive controls were native
      livers from two patients with unequivocal fulminant hepatitis B and from four
      patients with cirrhosis attributed to hepatitis C virus. Our negative findings
      suggest that, in the UK, acute liver failure attributed to sporadic non-A, non-B
      hepatitis most likely is caused by agent/s other than hepatitis B and C viruses.

PMID- 7814807
TI  - Role of the donor liver in the origin of platelet disorders and hyperfibrinolysis
      in liver transplantation.
AB  - We investigated the role of the donor liver in the origin of platelet disorders
      and hemostatic defects in liver transplantation. Eighteen pigs received an
      orthotopic or a heterotopic, auxiliary liver graft. Liver biopsies were taken for
      electron microscopic studies 5-10 min after reperfusion in nine animals. Blood
      samples were taken from the first hepatic outflow and from the systemic
      circulation before and 5 min after graft recirculation. Electron microscopy did
      not show any evidence of microthrombi or platelet aggregation in the graft,
      either after orthotopic liver transplantation or after heterotopic liver
      transplantation. Most blood platelets, which were lying free in the sinusoids,
      showed cell processes and many seemed to have lost their granulae, suggesting a
      degree of platelet activation. There were also signs of phagocytosis of platelets
      by the Kupffer cells. In the hepatic outflow, platelet count was significantly
      lower (p < 0.05) and fibrinolytic activity significantly higher (p < 0.01), than
      systemic post-reperfusion values. There were no important changes in the
      coagulation parameters. No significant changes were found between the effects on
      hemostasis of orthotopic and auxiliary graft reperfusion. In the second part of
      the study evidence for platelet activation was found after graft reperfusion in
      human liver transplantation. Plasma levels of platelet factor-4 and beta
      thromboglobulin increased significantly after graft reperfusion. These studies
      suggest that platelet disorders and increased fibrinolytic activity are the major
      components of the hemostatic defect after graft recirculation in liver
      transplantation. Sequestration of platelets in the graft is probably due to the
      accumulation of (activated and degranulated) platelets in the sinusoids and
      phagocytosis by Kupffer cells.

PMID- 7814808
TI  - Effects of glycyrrhizin on hepatitis B surface antigen: a biochemical and
      morphological study.
AB  - Glycyrrhizin, a major component of a herb (licorice), has been widely used to
      treat chronic hepatitis B in Japan. This substance improves liver function with
      occasional complete recovery from hepatitis; its effects on the secretion of
      hepatitis B surface antigen (HBsAg) were examined in vitro. Glycyrrhizin
      suppressed the secretion of HBsAg and accumulated it dose-dependently in
      PLC/PRF/5 cells. Its action was further analyzed and determined in the HBsAg
      expression system using the varicella-zoster virus. Glycyrrhizin suppressed the
      secretion of HBsAg, resulting in its accumulation in the cytoplasmic vacuoles in
      the Golgi apparatus area. HBsAg labeled with 35S-methionine and cysteine
      accumulated in the cells and its secretion was suppressed dose-dependently in
      glycyrrhizin-treated culture. The secreted HBsAg was modified by N-linked and O
      linked glycans but its sialylation was inhibited dose-dependently by
      glycyrrhizin. Thus glycyrrhizin suppressed the intracellular transport of HBsAg
      at the trans-Golgi area after O-linked glycosylation and before its sialylation.
      HBsAg particles were mainly observed on the cell surface in the glycyrrhizin
      treated culture but not in the untreated culture. This suggests that asialylation
      of HBsAg particles resulted in the novel surface nature of glycyrrhizin-treated
      HBsAg particles. We elucidated the unique mechanism of action of glycyrrhizin on
      HBsAg processing, intracellular transport, and secretion.

PMID- 7814809
TI  - Glucocerebrosidase for treatment of Gaucher's disease: first German long-term
      results.
AB  - Until recently, there was no specific therapy available for patients with
      Gaucher's disease. Since April 1991 a highly purified human placental preparation
      of glucocerebrosidase (Ceredase, Genzyme) has been available for clinical studies
      in Germany. Sequential deglycosylation of the native enzyme yields a mannose
      terminated preparation that may preferentially bind to the plasma membrane of
      macrophages. The present report analyzes the first German (and European) long
      term results with glucocerebrosidase therapy in five patients with type I
      Gaucher's disease (four women and one man, aged 29-40 years). All patients
      suffered from excessive enlargement of the liver and spleen with subsequent
      pancytopenia and from skeletal complications. Multiple pathological fractures had
      already occurred in three of the five patients, requiring several surgical
      procedures. Fatigue and asthenia were present in all patients. The initial dose
      of glucocerebrosidase was chosen according to the severity of complications in
      the individual patient (20-50 U/kg given i.v. every 2nd week) and was performed
      in the five patients for 12-18 months. After a few weeks all patients reported
      that fatigue and asthenia were markedly reduced. After 12 months, blood counts of
      erythrocytes, leukocytes and platelets had completely normalized in all but one
      of the patients. After 4-6 months a significant reduction in the sizes of liver
      and spleen could be observed in all patients. No further fractures occurred
      during treatment. Significant side-effects of glucocerebrosidase treatment did
      not occur. The new glucocerebrosidase preparation offers the first effective drug
      therapy for patients with Gaucher's disease. Although the treatment proved
      effective and harmless, it is, at least initially, very expensive.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7814810
TI  - Effects of ursodeoxycholic acid after 4 to 12 years of therapy in early and late
      stages of primary biliary cirrhosis.
AB  - Twenty-two patients with primary biliary cirrhosis were treated with
      ursodeoxycholic acid, 10 mg/kg per day. Fourteen patients with stages I/II were
      treated for 4-12 years (mean 7.5), and eight patients with stages III/IV for 5-12
      years (mean 6.5). Twelve of 13 patients with early stages became asymptomatic.
      Aminotransferases, cholestasis-indicating enzymes and IgM improved (p < 0.01) and
      remained low during the whole treatment period. Ursodeoxycholic acid was the
      predominant serum bile acid, and lithocholic acid did not increase in the serum
      but did increase in the stool. Of eight patients with stages III/IV, seven were
      symptomatic, and four became asymptomatic. In all eight patients, laboratory data
      improved. Of these eight patients three experienced haemorrhage from oesophageal
      varices, two had to be transplanted, and one of them died. In one patient splenic
      rupture occurred, and in three liver function tests deteriorated. Although the
      number of patients was small, this is the longest treatment period so far
      reported. Ursodeoxycholic acid had no side effects for up to 12 years, and in
      patients with early stages it seemed to have a beneficial effect on symptoms and
      the progression of the disease. However, even with up to 12 years of therapy,
      ursodeoxycholic acid did not cause antimitochondrial antibodies to disappear
      either in the early or in the late stages, it was unable to prevent rebound
      effects during therapy intermission even after more than 5 years of continuous
      therapy, there was no decisive influence on liver histology and it did not cure
      the disease. Finally, although ursodeoxycholic acid improved life quality and
      laboratory data in all patients with late stages of the disease, it did not
      prevent complications due to cirrhosis.

PMID- 7814811
TI  - Current seroepidemiological status of hepatitis A with a comparison of antibody
      titers after infection and vaccination.
AB  - The overall prevalence of anti-hepatitis A virus antibodies was 49.6% in 385
      inhabitants in Honda City, Japan in 1991. An approximately 50% prevalence rate
      occurred between 40 and 49 years of age. The prevalence of anti-HAV antibodies
      was significantly lower in 1991 than in 1982 in the age groups 20 to 29 years and
      30 to 39 years (p < 0.01), suggesting there has been no significant HAV infection
      since 1982. In addition, anti-HAV antibody titers of sera from convalescent
      hepatitis. A patients were compared with those from seropositive healthy subjects
      and from healthy subjects following administration of a lyophilized inactivated
      hepatitis A vaccine or immune serum globulin. Titers after vaccine administration
      were considerably higher than after immune serum globulin and, although lower
      than those obtained after natural infection, should be sufficient for protection
      against hepatitis A virus.

PMID- 7814812
TI  - The treatment effect of alpha interferon in chronic hepatitis B is independent of
      pre-treatment variables. Results based on individual patient data from 10
      clinical controlled trials. European Concerted Action on Viral Hepatitis
      (Eurohep).
AB  - Alpha interferon induces HBeAg seroconversion in about one third of treated
      patients and has become an established treatment of chronic hepatitis B. A number
      of smaller studies have suggested that response to treatment is more likely to
      occur in patients with higher levels of transaminases, with recent (adult) onset,
      a history of acute hepatitis, low levels of HBV DNA and in heterosexual males.
      The aim of this European co-operative study was to estimate the effect of alpha
      interferon more accurately and to evaluate the influence of host pre-treatment
      variables on the effect of interferon. Individual data were collected from 751
      patients from 10 controlled clinical trials on alpha interferon (lymphoblastoid
      or recombinant) treatment for chronic hepatitis B. Alpha interferon was
      administered to 496 patients, while 255 were untreated controls. Individual
      patient data were analysed by survival analysis (log rank test and Cox regression
      analysis), stratified by trial, with the disappearance of HBeAg as the major
      endpoint. The results showed that the HBeAg disappearance rate with or without
      interferon treatment was higher in patients with high aminotransferase levels,
      with a history of acute hepatitis and in male heterosexual patients disregarding
      HIV status. If HIV-positive patients were excluded, the effect of sexual
      orientation was not significant. Therapy with alpha interferon increased the a
      priori HBeAg disappearance rate by a factor of 1.76; the relative treatment
      effect of alpha interferon was independent of the tested pretreatment host
      variables, but dependent on the total (intended) interferon dose (low dose < or =
      200 MU/m2 increased HBeAg disappearance by a factor 1.37; medium/high dose > or =
      200 MU/m2 increased HBeAg disappearance by a factor 2.05). In conclusion, this
      meta-analysis suggests that the effect of alpha interferon is less than
      previously assumed and independent of pretreatment host variables tested. It
      confirms the higher therapeutic benefit of a total dose exceeding 200 MU/m2 and
      of selection of patients based on disease activity and immune reactivity.
      Although all patient seem to have the same relative benefit, the absolute benefit
      of alpha interferon treatment seems to be greatest in patients with high
      transaminase levels and with a history of acute hepatitis.

PMID- 7814813
TI  - Survival and prognostic factors in 366 patients with compensated cirrhosis type
      B: a multicenter study. The Investigators of the European Concerted Action on
      Viral Hepatitis (EUROHEP).
AB  - A multicenter longitudinal study was performed to assess the survival of
      hepatitis B surface antigen positive compensated cirrhosis, primarily in relation
      to hepatitis B virus replication and hepatitis delta virus infection, and to
      construct a prognostic index based on entry characteristics. This cohort study
      involved nine university medical centers in Europe. Three hundred and sixty-six
      Caucasian HBsAg positive patients with cirrhosis who had never had clinical
      manifestations of hepatic decompensation were enrolled and followed for a mean
      period of 72 months (6 to 202 months). Inclusion criteria were biopsy-proven
      cirrhosis, information on serum hepatitis B e antigen and antibody to hepatitis D
      virus at the time of diagnosis and absence of complications of cirrhosis. At
      entry 35% of the patients were HBeAg positive, 48% of the patients tested were
      HBV-DNA positive and 20% anti-HDV positive. Death occurred in 84 (23%) patients,
      mainly due to liver failure (45 cases) or hepatocellular carcinoma (23 cases).
      The cumulative probability of survival was 84% and 68% at 5 and 10 years,
      respectively. Cox's regression analysis identified six variables that
      independently correlated with survival: age, albumin, platelets, splenomegaly,
      bilirubin and HBeAg positivity at time of diagnosis. According to the
      contribution of each of these factors to the final model, a prognostic index was
      constructed that allows calculation of the estimated survival probability. No
      difference in survival of hepatitis D virus infected and uninfected patients was
      observed. Termination of hepatitis B virus replication and/or biochemical
      remission during follow up correlated with a highly significant better survival.
      These data show that in compensated cirrhosis B, hepatitis B virus replication,
      age and indirect indicators of poor hepatic reserve and established portal
      hypertension significantly worsen the clinical course of the disease, whereas
      hepatitis D virus infection does not influence the prognosis. The highly
      significant improvement in life expectancy following cessation of hepatitis B
      virus replication and biochemical remission favors antiviral therapy in those
      patients with a guarded prognosis, as estimated by a prognostic index.

PMID- 7814814
TI  - A European survey on the treatment of ascites in cirrhosis.
AB  - A questionnaire to assess the clinical choice of ascites treatment in cirrhosis
      was distributed to 1473 participants in an EASL meeting. The response rate (295,
      20%) was considered satisfactory in view of the heterogeneity of the persons
      attending this event. Most participants (86.4%) in the survey were hepatologists
      and gastroenterologists. The following conclusions of the survey are noteworthy:
      (1) The objective of ascites therapy was to eliminate completely or almost
      completely the ascitic fluid for 49% of responders and to decrease ascites volume
      to an acceptable level of patient comfort for 48%; (2) The classical progressive
      therapeutic schedule of ascites is rarely used; (3) Following mobilisation of
      ascites, most (82%) maintain patients on diuretic therapy to avoid reaccumulation
      of ascites; (4) Only 5% of participants did not use paracentesis to manage
      ascites in cirrhosis. This was the therapeutic procedure most frequently used for
      patients with refractory ascites; (5) Although the most acceptable definition of
      refractory ascites was ascites which cannot be mobilized by maximal medical
      treatment, a significant proportion of participants also considered that
      intractable ascites due to diuretic-induced complications and recidivant ascites
      should be included in the definition; (6) The proportions of participants
      prescribing prophylactic therapy, mainly low sodium diet, to compensated patients
      with and without a past history of ascites were 68% and 16%, respectively.

PMID- 7814815
TI  - Quantitation of HCV-replication using one-step competitive reverse transcription
      polymerase chain reaction and a solid phase, colorimetric detection method.
AB  - A solid phase assay for the colorimetric detection of competitively amplified HCV
      cDNA has been established and used to investigate clinical samples from patients
      with chronic hepatitis. The assay is based on the reduction in the amplification
      of an hepatitis C virus-related competitor molecule by wild-type hepatitis C
      virus during polymerase chain reaction. The internal standard contains a lac
      operator sequence, allowing the amount of amplified competitor to be determined
      using a lac I-repressor/beta-galactosidase fusion protein. The reduction in the
      amplification of competitor is dependent upon the concentration of HCV-RNA in the
      original sample. External hepatitis C virus wild-type standards are used to
      calibrate each concurrently tested set of patients. We present and discuss the
      potential benefit, but also the limitations of this new approach for quantifying
      hepatitis C virus viremia. In 47 serum samples from 28 patients with chronic
      hepatitis C virus infection, including five repeatedly tested alpha HCV positive
      patients under interferon therapy, viral titer was determined. Sera from nine
      healthy blood donors served as controls. The sensitivity and specificity of this
      procedure are identical to those of conventional nested polymerase chain
      reaction. As both internal and external standards are used in every assay and
      final detection of amplicons can be carried out in microtiter plates, this
      reliable and time-saving test system may be routinely applied for monitoring
      antiviral treatment or for studying the relation of plus- and minus-stranded HCV
      RNA in infected tissues.

PMID- 7814816
TI  - Reciprocal gamma-glutamyl transferase and cystathionase activity in guinea pig,
      rat and human liver.

PMID- 7814817
TI  - Normal technetium 99m diphosphonate bone scintigraphy in skeletal metastases from
      hepatocellular carcinoma.

PMID- 7814818
TI  - Transjugular intrahepatic portosystemic shunt improves liver function in veno
      occlusive disease.

PMID- 7814819
TI  - Iatrogenic gallstone with dipyridamole.

PMID- 7814820
TI  - Incidence of hepatitis C virus in Egyptians.

PMID- 7814821
TI  - The therapeutic benefit of vitamin E in patients with liver disease.

PMID- 7814822
TI  - A double-blind comparison of venlafaxine and fluoxetine in patients hospitalized
      for major depression and melancholia. The Venlafaxine French Inpatient Study
      Group.
AB  - The antidepressant efficacy and short-term safety of venlafaxine and fluoxetine
      were compared in 68 patients hospitalized with major depression and melancholia.
      Venlafaxine was superior in efficacy to fluoxetine; total scores for both the
      MADRS and the HAM-D were significantly (p < or = 0.05) lower in the venlafaxine
      group than in the fluoxetine group at Weeks 4 and 6. Overall tolerance was
      similar for the two treatments.

PMID- 7814823
TI  - Differential acute psychomotor and cognitive effects of diazepam on long-term
      benzodiazepine users.
AB  - The aim of this study is to determine whether long-term use (5-20 years) of
      therapeutic doses of diazepam (5-20 mg/day) in anxious patients (n = 28) is
      associated with tolerance to its psychomotor and cognitive effects. Patients were
      tested at baseline, before and after a 10 mg oral dose of diazepam during chronic
      use, and at 3 weeks and 10 months after benzodiazepine (BZ) discontinuation. The
      effects of a single i.v. dose of flumazenil (1 mg administered 5 days before
      baseline) on reversing tolerance were also assessed. No acute effect of diazepam
      was observed on the psychomotor performance of patients both under BZ treatment
      and after short- and long-term discontinuation, suggesting persistence of
      tolerance. In contrast, acute effects of diazepam were observed in memory
      measures at all times. Given subjects' very prolonged BZ use, it is possible to
      predict that tolerance to the memory effects never fully develops. Flumazenil
      administration did not reverse tolerance. This suggests that neuroadaptative
      mechanisms, other than benzodiazepine receptor set-point shift, occur after long
      term use.

PMID- 7814825
TI  - Fluoxetine attenuates alcohol intake and desire to drink.
AB  - Several serotonin uptake inhibitors, including the long-acting fluoxetine, have
      been found to decrease alcohol intake in moderately dependent alcoholics. While
      the mechanism of their effect is not fully elucidated, a previous study with
      citalopram indicated that decreased desire to drink may be an important factor.
      Therefore, we tested fluoxetine effects on alcohol intake and desire to drink in
      a placebo-controlled study. Subjects, recruited by advertisement, were
      mildly/moderately dependent alcoholics (12 male, four female, aged 19-59 years,
      healthy, non-depressed) who did not believe they had a drinking problem and were
      not requesting treatment. After a 1 week baseline they received, single-blind, 2
      weeks placebo followed by 2 weeks fluoxetine 60 mg/day. As out-patients, subjects
      recorded daily standard drinks (13.6 g ethanol) and rated interest, desire,
      craving and liking for alcohol biweekly. Each out-patient period was immediately
      followed by a double-blind experimental drinking session. Out-patient daily
      drinks slightly decreased during fluoxetine to 6.6 +/- 0.9 (mean +/- S.E.M.)
      compared with during placebo (7.16 +/- 0.95, p = 0.07, N.S.) and baseline (7.18
      +/- 1.0, p > 0.1, N.S.). Desire, interest and craving for alcohol decreased
      during fluoxetine vs placebo baseline (p < 0.05), but not vs placebo. Appetite
      loss and decrease in food intake (p < 0.01, fluoxetine vs placebo) correlated
      with each other (r = 0.91, p < 0.01) but neither correlated with decrease in
      alcohol intake (appetite: r = 0.26, N.S.; food intake: r = 0.22, N.S.). Weight
      loss occurred during fluoxetine (p < 0.05 vs placebo) but did not correlate with
      decrease in alcohol intake (r = 0.1, N.S.). In the experimental drinking sessions
      after placebo and fluoxetine treatments subjects rated their desire for each of
      18 mini-drinks (each one-third of a standard drink) offered at 5 min intervals.
      Fluoxetine decreased desire to drink throughout the sessions; both mean and
      maximum desire ratings were lower after fluoxetine than after placebo (ANOVA, p <
      0.05). Therefore, fluoxetine seems to have a robust effect on decreasing desire
      for alcohol. We propose that in the absence of intention by subjects to reduce
      drinking, their habitual drinking patterns mitigated against reduced consumption
      in the out-patient phase. However, fluoxetine could be a useful adjunct for
      patients in a treatment context who are motivated to reduce their drinking.

PMID- 7814824
TI  - Lack of amnestic, psychotomimetic or impairing effect on psychomotor performance
      of eliprodil, a new NMDA antagonist.
AB  - The possible effects on memory, psychomotor performance and mood of eliprodil, a
      new non-competitive NMDA receptor antagonist acting through the polyamine
      modulatory site, was assessed in a randomized, double-blind, cross-over, placebo
      controlled study involving 11 healthy young male volunteers. Eliprodil 30 mg, a
      placebo and midazolam 15 mg, a positive control, were administered as a single
      oral dose at 1 week wash-out intervals. Objective tests evaluated both memory
      (Sternberg memory scanning and paired words for short-term memory, delayed free
      recall of pictures for long-term memory) and psychomotor functions and arousal
      (critical flicker fusion threshold, choice reaction time, body sway). Mood was
      assessed using self-ratings (LARS, POMS, ARCI). Statistical analysis was
      performed using an ANOVA with pairwise comparisons using Tukey's method. A single
      dose of eliprodil 30 mg was free of any detrimental effect on memory and skilled
      performance and did not produce either subjective sedation or excitation or
      psychotomimetic effects in comparison with placebo. In contrast, a single dose of
      midazolam 15 mg induced a marked impairment in psychomotor performance and
      cognitive functions (significant reduction in CFF, increase in CRT and body sway,
      disruption of short- and long-term memory). The potent sedative activity of
      midazolam, peaking 1 to 3 h post-dose, was confirmed by subjective evaluation and
      had disappeared 8 h post-dose.

PMID- 7814826
TI  - The effects of administration of mCPP on psychological, cognitive,
      cardiovascular, hormonal and MHPG measurements in human volunteers.
AB  - m-Chlorophenylpiperazine (mCPP) is a metabolite of the antidepressant trazodone
      which has been widely used in psychopharmacology research as a probe of serotonin
      (5-hydroxytryptamine; 5-HT) function. However, in addition to binding at 5-HT
      receptors it also binds strongly to alpha 2-adrenoceptors, and it is conceivable
      that some of the physical and psychological symptoms previously reported
      following mCPP infusion are due to effects upon central noradrenergic
      neurotransmitter function. In this double-blind placebo-controlled balanced
      crossover study in 12 healthy male volunteers we have examined the effects of
      infusion of mCPP (0.08 mg/kg over 2 min) on symptoms of anxiety, cognitive
      performance, pulse and blood pressure, and plasma concentrations of
      adrenocorticotrophic hormone (ACTH), cortisol, prolactin, growth hormone, and the
      noradrenaline metabolite 3-methoxy-4-hydroxyphenyl glycerol (MHPG). The results
      confirm previous findings that in humans mCPP causes significant increases in the
      symptoms of anxiety, and in the plasma concentrations of cortisol, prolactin and
      growth hormone. In addition, our results demonstrate that mCPP causes no
      significant changes in cognitive performance, in pulse or systolic blood
      pressure, or in the plasma concentration of MHPG. Since pulse, systolic blood
      pressure and MHPG plasma concentrations all to some degree reflect central
      noradrenergic activity, we believe it unlikely that the psychological and
      hormonal effects of mCPP are due primarily to effects on noradrenergic
      neurotransmission. Further studies to address this specific issue are needed,
      however, before firm conclusions can be reached.

PMID- 7814827
TI  - Effect of zimeldine and its metabolites on [3H]thymidine incorporation in
      lymphocyte cultures from psychiatric patients with or without a hypersensitivity
      reaction during zimeldine therapy.
AB  - Lymphocyte transformation test (LTT) was applied to 28 patients who had developed
      a hypersensitivity syndrome (HSS) during treatment with the antidepressant drug
      zimeldine. Twenty-seven patients treated with zimeldine without any symptom of an
      HSS were matched controls. Zimeldine and its metabolites norzimeldine and CPP 200
      all induced statistically significant increased [3H]thymidine incorporation in
      cultured lymphocytes from the HSS patients compared with the controls,
      norzimeldine being the most potent inducer. The results indicate an
      immunoreactive process in the development of the HSS induced by zimeldine.

PMID- 7814828
TI  - Eltoprazine in aggressive mentally handicapped patients: a double-blind, placebo-
      and baseline-controlled multi-centre study. The Eltoprazine Aggression Research
      Group.
AB  - The efficacy of eltoprazine, a mixed 5-HT1 agonist, in treating aggressive
      behaviour in mentally handicapped patients was evaluated in a double-blind,
      placebo- and baseline-controlled study. In the total sample of 160 patients who
      entered the 8 week double-blind treatment phase, efficacy was not demonstrated.
      Also in a 28 week double-blind follow-up study, efficacy could not be
      demonstrated. Post-hoc exploratory analyses suggested eltoprazine was
      significantly better than placebo in reducing aggression scores of a subgroup of
      severely aggressive patients. There was no evident relationship between the
      plasma level of eltoprazine and therapeutic effect or safety and tolerance. The
      overall safety and tolerance of chronic eltoprazine treatment was good. In the
      discussion, several issues and pitfalls of aggression research are dealt with.

PMID- 7814829
TI  - The importance of accidents in evaluating the cost of SSRIs: a review.
AB  - Economic studies attempting to justify the increased cost of new antidepressants
      such as the SSRIs are often difficult to interpret, marginal benefits hinging on
      minute differences in assumptions and interpretation. Studies to date have
      focused largely upon the costs of treatment failure, which in turn relates to
      compliance rates. A missing factor is the cost of accidents, especially serious
      road traffic accidents. Most tricyclic antidepressants seriously impair driving
      performance, even more so than alcohol or benzodiazepines, whilst SSRIs do not.
      With moves towards maintenance and continuation therapy for depression, patients
      on tricyclics remain at long-term risk for such accidents. Cost savings from
      reducing the rate of accidents could more than pay for the increased costs of
      SSRIs.

PMID- 7814830
TI  - The effect of fluoxetine on sleep: a longitudinal, double-blind polysomnographic
      study of healthy volunteers.
AB  - Fluoxetine, a selective inhibitor of serotonin (5-HT) uptake, was compared with
      placebo in a randomized double-blind longitudinal trial in 12 healthy volunteers.
      Sleep polygraphic recordings were performed at home twice before and once after 6
      days of medication. After 6 days fluoxetine significantly decreased the amount of
      rapid eye movement (REM) sleep. The sleep-onset latency and REM latency were
      increased, but there was no significant increase in the amount of awakenings
      during night. The relative proportion of stages 2 and 3 increased after
      fluoxetine administration, although there was no significant change with regard
      to total amount of slow-wave sleep. Fluoxetine did not induce prominent eye
      movements during non-rapid eye movement (NREM) sleep in this study. Results of
      the subjective assessment revealed tendencies of improved sleep and well-being in
      the fluoxetine group. It is concluded that a comparatively small dose of
      fluoxetine (20 mg/day) causes the same type of changes in REM sleep which are
      characteristic of most antidepressive drugs.

PMID- 7814831
TI  - Clozapine and urinary incontinence.
AB  - Urinary incontinence may occur in patients with severe mental illness. Psychosis
      and neuroleptic medication have both been implicated, but there has been a lack
      of systematic evaluation of the precise relationship between these phenomena.
      Incontinence has been recognized as a complication of clozapine treatment and we
      examined this in 16 consecutively treated patients. Thirteen were established on
      therapeutic doses, one of whom was excluded from further study due to pre
      existing incontinence. Retrospective assessment revealed that nocturnal
      incontinence was experienced by five of the remaining 12 patients, occurring in
      the first 3 months of treatment and resolving spontaneously in all cases.
      Incontinence was documented in the case notes in only one of the five cases and
      there was a tendency for affected patients to be embarrassed and reluctant to
      report it to staff. Specific enquiry may be necessary to elicit this phenomenon
      and incontinence should be considered as a possible factor in poor compliance
      with clozapine.

PMID- 7814832
TI  - Flumazenil effects on growth hormone response to gamma-hydroxybutyric acid.
AB  - Gamma-hydroxybutyric acid (GHBA) has been recently introduced for alcohol
      detoxication but few data are available concerning the central mechanism of
      action of this gamma-aminobutyric acid (GABA) catabolite. GHBA ability to
      stimulate growth hormone (GH) and prolactin (PRL) secretion has been reported:
      the involvement of GABA, dopamine or serotonin systems acting on pituitary
      hormones has been hypothesized. In the present study we investigated GH and PRL
      responses to GHBA with or without flumazenil (a benzodiazepine receptor
      antagonist) i.v. pretreatment. Our study included nine male healthy volunteers
      (aged 23.2 +/- 2.5 years) who were submitted to three tests in random order: (1)
      oral GHB administration; (2) oral GHBA and i.v. flumazenil administration; (3)
      oral placebo and i.v. saline administration. Blood samples for GH and PRL assays
      were collected during the three tests at -15, 0, 15, 30, 45, 60 and 90 min. GHBA
      induced a significant increase in GH plasma levels; flumazenil pretreatment
      antagonized GHBA action on GH secretion. No changes were obtained with placebo
      and saline administration. A subpopulation of GABA receptors or GHBA-specific
      receptors seems to be involved in GHBA action. The benzodiazepine receptor
      antagonist flumazenil was able to influence the sensitivity and the
      neuroendocrine consequences of GHBA binding site stimulation.

PMID- 7814833
TI  - Dermatologic manifestations of infections in diabetics.
AB  - In patients with diabetes, the cutaneous signs of the infections that occur are
      multiple. A high index of suspicion for infection must be maintained while caring
      for the diabetic patient. Early recognition and prompt treatment will hopefully
      prevent some of the devastating outcomes that are seen in this group of patients.

PMID- 7814834
TI  - Dermatologic manifestations of sexually transmitted diseases other than HIV.
AB  - This article focuses on the common skin manifestations of sexually transmitted
      diseases. A number of unusual skin lesions associated with these diseases are
      shown, and pathogenesis and treatment are briefly presented. This article will be
      most useful as a reference for the formulation of the differential diagnosis of
      genital area skin lesions.

PMID- 7814835
TI  - Dermatologic manifestations of HIV infection and AIDS.
AB  - Infection with HIV can result in many cutaneous disorders, some of which may be
      the presenting sign of the disease. The cutaneous manifestations may be
      infectious or noninfectious. This article reviews the numerous cutaneous
      infectious findings, neoplasms, and dermatoses seen in HIV-infected individuals.

PMID- 7814837
TI  - Dermatologic manifestations of nosocomial infections.
AB  - There is no substitute for preventing dermatologic infection in a hospitalized
      patient by maintaining intact, well nourished skin. The integrity of the
      integument becomes assaulted on a daily basis from a variety of methods. Measures
      to lessen this risk can be undertaken, but it may not be totally preventable. The
      phenomenon of infected desquamated squamous cells being dispersed into the
      environment by patients and health care workers is one that deserves further
      study. If this proves to be an important factor, hospital spread of bacteria may
      indeed be unavoidable. It is hoped that this review will serve as a starting
      point in an area short on clinical data. Further study into this arena is clearly
      needed.

PMID- 7814836
TI  - Dermatologic manifestations of antimicrobial adverse reactions with special
      emphasis on topical exposure.
AB  - Topical application of antimicrobial agents can lead to an increased risk of
      systemic reactions. Adverse reactions can occur with topical antifungals and
      antiviral agents in addition to antibiotics.

PMID- 7814838
TI  - Dermatologic manifestations of infectious diseases in cardiac transplant
      patients.
AB  - Infection remains a significant cause of morbidity and mortality in cardiac
      transplant patients. Skin infections are not uncommon in these patients. Although
      usually caused by secondary dissemination after initial infection of another
      organ system, some skin infections may be primary infections, such as bacterial
      infections caused by the use of intravenous catheters or fungal infections in
      severely immunosuppressed patients. Nevertheless, the presence of skin lesions in
      a transplant patient may indicate infection in a primary site or another deep
      seated focus of infection.

PMID- 7814840
TI  - Dermatologic manifestations of nontuberculous mycobacterial diseases.
AB  - Various nontuberculous mycobacteria can cause infection of skin and soft tissues.
      These organisms are also known as atypical mycobacteria, anonymous mycobacteria,
      and mycobacteria other than tuberculosis. These organisms are much more common
      causes of cutaneous infection than Mycobacterium tuberculosis. Infections caused
      by nontuberculous mycobacteria are frequently misdiagnosed because clinicians
      fail to include them in the differential diagnosis of chronic skin infection.

PMID- 7814839
TI  - Dermatologic manifestations of infections in neutropenic patients.
AB  - Skin lesions may serve as the site of origin for disseminated infection in
      neutropenic patients or result as a secondary consequence of disseminated
      infection from another source. It is important to recognize the characteristic
      skin lesions associated with infections, such as those caused by Clostridium spp,
      Candida spp, and Pseudomonas aeruginosa, so that appropriate therapy is initiated
      promptly. Unfortunately, therapy for some of these infections, especially those
      caused by fungi, is unsatisfactory in persistly neutropenic patients.
      Antibacterial, antifungal, and antiviral prophylaxes have caused a significant
      reduction in some of these infections.

PMID- 7814841
TI  - Dermatologic manifestations of arthropod-borne diseases.
AB  - The arthropod-borne rickettsial, borrelial, and bacterial diseases of North
      America are a diverse group of disorders that produce a wide variety of cutaneous
      abnormalities. These dermatologic abnormalities are often valuable clinical clues
      that may reveal or suggest the correct diagnosis to the astute clinician. We
      review the usual and unusual dermatologic manifestations of Rocky Mountain
      spotted fever, murine and sylvatic typhus, rickettsialpox, ehrlichiosis, Lyme
      disease, tick-borne relapsing fever, Colorado tick fever, and tularemia. In some
      of these diseases, skin manifestations may be diagnostic; in others, dermatologic
      findings may be the initial and only clues that leads to the initiation of life
      saving therapy. In other arthropod-borne infections, the appearance or evolution
      of the skin rash may be characteristic enough to suggest the proper diagnosis.

PMID- 7814843
TI  - Bibliography of the current world literature in hypertension.

PMID- 7814842
TI  - Dermatologic manifestations of parasitic diseases.
AB  - The skin being exposed to the environment is commonly the portal of entry for
      parasites. Infections with parasites characteristically produce cutaneous lesions
      as well as systemic disease in humans. In the past, parasitic diseases were
      limited to their endemic areas. With the relative ease of worldwide travel,
      however, they are appearing with increasing frequency in the United States and
      other developed countries. This article describes the characteristic cutaneous
      findings of parasitic diseases that physicians in the United States may encounter
      in their medical practice.

PMID- 7814844
TI  - Beyond genetic markers: hypertension genes.

PMID- 7814845
TI  - Prognostic value of ambulatory blood pressure monitoring.

PMID- 7814846
TI  - Hypertension and stroke.

PMID- 7814847
TI  - Identification of vascular renin-binding proteins by chemical cross-linking:
      inhibition of binding of renin by renin inhibitors.
AB  - OBJECTIVE: To investigate the mechanism of tissue uptake of renin. DESIGN:
      Angiotensin peptide formation in tissues is dependent on kidney-derived renin,
      leading us to hypothesize that tissues possess a mechanism for uptake of renin
      from plasma. METHODS: The binding of [125I]-labelled renin to membranes prepared
      from various rat tissues was examined. [125I]-labelled renins were cross-linked
      to membranes with disuccinimidyl suberate and analysed by sodium dodecyl sulphate
      polyacrylamide gel electrophoresis followed by autoradiography. RESULTS:
      Mesenteric artery membranes bound both [125I]-labelled rat renin and [125I]
      labelled mouse submandibular gland renin. Cross-linking experiments showed two
      bands, one of relative molecular mass approximately 105,000 and the other of
      approximately 75,000. After taking into account the molecular weight of renin,
      these bands represent renin-binding proteins of relative molecular mass
      approximately 70,000 and approximately 40,000, respectively. The highest level of
      these binding proteins was in the mesenteric artery; lower levels were found in
      the aorta, lung and renal medulla. Renin-binding proteins were also identified in
      membranes prepared from cultured rat aortic smooth muscle cells. No binding
      proteins were identified in the kidney cortex, heart, adrenal capsule, adrenal
      medulla, peri-aortic brown adipose tissue, uterus or pituitary. Binding of renin
      to mesenteric artery membranes was prevented by inhibitors of renin enzymatic
      activity (H-77 and SQ 30697); this effect of H-77 showed a dose-dependence
      parallel to the inhibition of renin activity by this compound, suggesting that
      the binding of H-77 to the active site of renin prevents its binding to the
      membranes. CONCLUSIONS: These studies provide evidence for a vascular renin
      binding mechanism, which may play a role in the generation of angiotensin
      peptides in vasculature, and may thus be a determinant of blood pressure.
      Moreover, one of the actions of inhibitors of renin enzymatic activity in vivo
      may be to prevent the binding of renin to the vasculature.

PMID- 7814848
TI  - The response to arachidonic acid before and after non-steroidal anti-inflammatory
      drugs in normotensive and hypertensive rats.
AB  - OBJECTIVE: To establish equivalent doses of four non-steroidal anti-inflammatory
      drugs (NSAID) in normotensive and hypertensive rats using inhibition of the fall
      in blood pressure produced by the injection of arachidonic acid as the measure of
      equivalence. DESIGN: An experimental study using two rat models of hypertension
      and their normotensive controls. METHODS: Two rat models of hypertension
      (spontaneously hypertensive rats and two-kidney, one clip rats) and their
      normotensive controls were studied. The change in blood pressure after
      intravenous injection of arachidonic acid was measured in anaesthetized rats.
      Blood pressure was measured from a carotid artery cannula, attached to a pen
      recorder. Dose-response curves for the effect of arachidonic acid were
      established in each type of rat, then the effects of different doses of four
      NSAID (indomethacin, piroxicam, naproxen and sulindac) on these responses were
      measured. RESULTS: Arachidonic acid produced a dose-dependent fall in blood
      pressure in all rats. However, both types of hypertensive rats sustained a larger
      fall in blood pressure for a given dose of arachidonic acid than did the
      normotensive controls. Doses of NSAID were found that inhibited this response in
      Wistar rats. However, the doses of NSAID that were equivalent in normotensive
      rats were not equivalent in either type of hypertensive rat; indomethacin had a
      greater inhibitory effect. As far as could be established, this was not due to
      differences in the metabolism of the NSAID between normotensive and hypertensive
      rats. CONCLUSIONS: The arachidonic acid response can be used as a method of
      establishing equivalent doses of NSAID in normotensive and hypertensive rats.
      Hypertensive rats appear to be more sensitive to the effects of arachidonic acid
      than normotensive rats, independent of the model of hypertension. Doses of NSAID
      that are equivalent in normotensive rats are not equivalent in hypertensive rats.
      Indomethacin is more effective in attenuating the effect of arachidonic acid,
      possibly due to actions other than inhibition of cyclo-oxygenase.

PMID- 7814849
TI  - Calcium metabolic changes and calbindin-D in experimental hypertension.
AB  - OBJECTIVE: To examine renal and intestinal calbindin-D in relation to calcium
      metabolic changes in three different models of experimental hypertension. DESIGN:
      Spontaneously hypertensive rats (SHR), hypertension-prone Dahl salt-sensitive
      (Dahl-S) rats and the Goldblatt two-kidney, one clip rat model of renovascular
      hypertension were examined. RESULTS: Both prehypertensive and hypertensive SHR
      had significantly lower concentrations of both renal calbindin-D28k and
      intestinal calbindin-D9k than Wistar control rats. This was accompanied by
      hypocalcaemia, hypomagnesaemia and increased plasma 1,25(OH)2 vitamin D levels.
      Induction of hypertension in Dahl-S rats reduced intestinal calbindin-D9k and
      increased plasma levels of 1,25(OH)2 vitamin D, while renal calbindin-D28k
      levels, plasma calcium levels and plasma magnesium levels were unchanged.
      Renovascular hypertension was associated with a significant increase in the
      intestinal calbindin-D9k, plasma 1,25(OH)2 vitamin D, parathyroid hormone and
      magnesium levels, while renal calbindin-D2k, plasma calcium and phosphorus levels
      were unaffected. CONCLUSIONS: These three models of experimental hypertension
      have clearly demonstrated three separate patterns in the regulation of renal and
      intestinal calbindin-D, which relate to different alterations of factors involved
      in calcium and magnesium metabolism. In all three models hypertension was
      accompanied by a significant increase in plasma concentrations of 1,25(OH)2
      vitamin D. Only rats with renovascular hypertension showed increased intestinal
      calbindin-D9k levels, whereas reduced concentrations were found in the SHR and in
      the hypertensive Dahl-S rats. This indicates the existence of a resistance at the
      cellular level to 1,25(OH)2 vitamin D affecting the expression of calbindin-D in
      both SHR and Dahl-S rats.

PMID- 7814850
TI  - Mechanistic analysis of renal protection by angiotensin converting enzyme
      inhibitor in Dahl salt-sensitive rats.
AB  - OBJECTIVE: To investigate whether and how renin-angiotensin inhibition attenuates
      renal injury seen in salt-induced hypertension in Dahl salt-sensitive (Dahl-S)
      rats. METHODS: Dahl-S rats fed a high-salt (4% sodium chloride) diet for 6 weeks
      were treated with the angiotensin converting enzyme (ACE) inhibitor alacepril or
      the angiotensin receptor antagonist losartan for 4 weeks. Functional and
      morphological alterations in the kidney were investigated. RESULTS: Alacepril
      decreased systolic blood pressure (SBP). This SBP reduction was associated with
      the attenuation of cardiac and aortic wall hypertrophy and that of proteinuria
      and urinary N-acetyl-beta-D-glucosaminidase excretion. Kidney injuries, e.g.
      glomerular, arterial and tubular damage, were improved with alacepril treatment.
      Losartan decreased SBP to the same extent as alacepril, but neither renal
      function nor morphological structure was improved as was the case with alacepril.
      The response of the renal eicosanoid system to alacepril was inadequate, but
      cyclic GMP excretion, an indicator of nitric oxide formation, was significantly
      enhanced and lipid peroxidation in the kidney was decreased. CONCLUSIONS: The
      beneficial effects of ACE inhibition on the renal injury in Dahl-S rats outrange
      those induced by the receptor antagonism. This might be due to multiple factors
      including an increased vasodepressor eicosanoid system, enhanced nitric oxide
      formation and possible inhibition of oxygen radical generation in the injured
      renal tissues.

PMID- 7814851
TI  - Indomethacin and cyclosporin together produce marked renal vasoconstriction in
      humans.
AB  - OBJECTIVE: To test the hypothesis that an imbalance in intrarenal prostaglandins
      plays a role in cyclosporin-induced nephrotoxicity. METHODS AND RESULTS:
      Indomethacin was given in combination with cyclosporin to healthy volunteers.
      Cyclosporin alone (10 mg/kg twice a day) for 4 days had no effect on effective
      renal plasma flow (ERPF) and glomerular filtration rate but 4 days of therapy
      with cyclosporin (10 mg/kg twice a day) and indomethacin (50 mg twice a day) in
      combination resulted in a 37% fall in glomerular filtration rate and a 32% fall
      in ERPF. This suggests that autoregulatory mechanisms, possibly involving renal
      prostaglandins, may participate in counteracting the tendency for cyclosporin
      induced renal vasoconstriction in humans. Cyclosporin increased systemic blood
      pressure acutely, and this was not influenced by indomethacin even though
      indomethacin on its own caused sodium retention. This suggests that, in contrast
      to the renal vasculature, the systemic vascular response to cyclosporin is
      neither augmented nor buffered by prostaglandins. CONCLUSION: The reduction in
      intrarenal prostaglandins clearly played a key role in the development of
      cyclosporin-induced renal vasoconstriction, but we could not demonstrate a role
      for prostaglandins or for sodium retention in the initiation of cyclosporin
      induced hypertension.

PMID- 7814852
TI  - Comparison of calcium, magnesium-ATPase activity and membrane fluidity in
      patients with essential hypertension and in normotensive controls.
AB  - OBJECTIVES: To measure calcium,magnesium-ATPase (Ca-ATPase) activity and membrane
      fluidity in patients with essential hypertension compared with normotensive
      subjects; to investigate the interrelationship between membrane fluidity and the
      activity of the Ca-ATPase; and to assess the importance of circulating lipids on
      the Ca-ATPase and membrane fluidity. METHODS: Ca-ATPase and membrane fluidity
      were measured in erythrocyte membranes. Kinetic parameters [maximal activity
      (Vmax), apparent dissociation constant and allosteric number] of the Ca-ATPase
      activity were measured, in the presence of saturating calmodulin, in 38
      normotensives and 57 essential hypertensives. Fluorescent polarization
      anisotropy, as an index of membrane fluidity, was measured, using the fluorescent
      probes 1,6-diphenyl-1,3,5-hexatriene (DPH) and trimethylammonium DPH (TMA-DPH) in
      37 normotensives and 44 hypertensives. Of these 22 were paired for age, sex and
      race. RESULTS: There was no significant difference in the Vmax and allosteric
      number of the Ca-ATPase between the normotensives and hypertensives, but there
      was a trend for the hypertensives to have a reduced calcium affinity. In
      contrast, hypertensive subjects had significantly lower membrane fluidity. Sex
      and serum triglycerides level were important determinants of membrane fluidity in
      both groups. Comparisons between normotensives and hypertensives demonstrated
      decreased fluidity in the hypertensives independent of sex and serum
      triglycerides level, although the differences, especially with TMA-DPH, were more
      pronounced in the females. In both groups there were negative correlations
      between Vmax and both DPH and TMA-DPH anisotropy. CONCLUSION: The present study
      demonstrates that essential hypertension is associated with a generalized
      alteration in the erythrocyte membrane physical and chemical properties. However,
      despite the positive correlation between Vmax and membrane fluidity, the present
      study also demonstrates that essential hypertension is not associated with a
      major abnormality in the activity of the erythrocyte Ca-ATPase in isolated
      membranes.

PMID- 7814854
TI  - Ambulatory blood pressure and microalbuminuria in essential hypertension: role of
      circadian variability.
AB  - OBJECTIVE: To assess the relationship of subclinical urinary albumin excretion
      with ambulatory and circadian variability of blood pressure. DESIGN AND METHODS:
      Patients with essential hypertension (82 males and 59 females, mean +/- SD age
      38.9 +/- 7.3 years) who had never been previously treated for hypertension were
      included in the study. Patients with nephropathy or diabetes mellitus,
      hyperglycemia > 120 mg/dl, glomerular filtration rate < 80 ml/min per 1.73 m2,
      urinary tract infection and positive dipstick for albumin or glucose were
      excluded. Twenty-four-hour ambulatory blood pressure monitoring on a regular
      working day using an oscillometric device was performed. Twenty-four-hour urinary
      albumin excretion was measured on two separate days using an immunonephelometric
      assay. RESULTS: Microalbuminuric patients (urinary albumin excretion 30-300 mg/24
      h, n = 31) had significantly higher mean ambulatory systolic blood pressure (SBP)
      and diastolic blood pressure (DBP) than those with normoalbuminuria (urinary
      albumin excretion < 30 mg/24 h, n = 96) during the 24-h, daytime (0800-2200 h)
      and night (2400-0600 h) periods, whereas for office blood pressure only DBP was
      significantly higher. Urinary albumin excretion was positively correlated with
      the means of SBP and DBP. Multiple regression analysis similarly confirmed that
      DBP during daytime was positively and day:night ratio of DBP inversely associated
      with urinary albumin excretion independent of age, sex and other parameters of
      ambulatory blood pressure. CONCLUSIONS: In conclusion, the present study
      indicates that, in middle-aged essential hypertensive patients, the presence of
      microalbuminuria is a marker for the presence of higher values of blood pressure
      throughout a 24-h period.

PMID- 7814853
TI  - Platelet alpha 2-adrenoceptors and diurnal changes of platelet aggregability in
      hypertensive patients.
AB  - OBJECTIVE: To analyse whether platelets from hypertensive patients have an
      increased responsiveness to aggregating agents during morning hours and whether
      these changes might be related to concurrent changes in platelet membrane alpha 2
      adrenoceptor characteristics, plasma catecholamine and cortisol levels, and blood
      pressure values. DESIGN AND METHODS: Blood samples from 14 mild-to-moderate
      essential hypertensive males were collected in the morning (0700-0900 h) and the
      evening (1900-2100 h) to determine platelet aggregability responses to adrenaline
      and ADP, platelet alpha 2-adrenoceptor number and binding affinity to [3H]
      yohimbine, plasma catecholamines and cortisol. During the same day patients
      underwent 24-h ambulatory blood pressure monitoring. RESULTS: The lowest
      concentration of adrenaline required to induce biphasic aggregation was
      significantly lower in the morning than in the evening, indicating an increased
      morning platelet aggregability to adrenaline; the minimum ADP concentration
      inducing aggregation was similar in morning and evening samples. There were no
      significant differences between morning and evening samples in platelet alpha 2
      adrenoceptor number and binding affinity. Plasma adrenaline, noradrenaline and
      cortisol levels were higher in the morning than in the evening, but no
      correlation was observed between hormonal changes and the morning increase in
      platelet sensitivity to adrenaline. Ambulatory blood pressure recording showed
      abrupt morning elevations in systolic and diastolic blood pressures over sleeping
      values. However, morning blood pressure readings were not significantly different
      from those recorded during the rest of the day and in the evening. The morning
      rise in mean arterial pressure displayed a significant inverse correlation with
      the increased platelet sensitivity to adrenaline that was observed during the
      same hours. CONCLUSIONS: The results indicate that the increased morning
      responsiveness to adrenaline that was observed in platelets obtained from
      hypertensive patients does not appear to be mediated by changes in the
      characteristics of platelet membrane alpha 2-adrenoceptors, but morning blood
      pressure elevations might play some role in inducing this platelet hyper
      reactivity.

PMID- 7814855
TI  - Angiotensin converting enzyme insertion/deletion polymorphism: association with
      ethnic origin.
AB  - OBJECTIVE: To determine the distribution of the insertion/deletion (I/D)
      polymorphism of the angiotensin converting enzyme (ACE) gene in several ethnic
      groups: Caucasian Europeans, Black Nigerians, Samoan Polynesians and Yanomami
      Indians. RESULTS: The ratio of the frequencies of the II, ID and DD genotypes
      were 1:2:1 in the Europeans, but there was a tendency towards a higher frequency
      of the D allele in the Nigerians. In contrast, the Samoans and the Yanomami
      Indians displayed a much higher frequency of the I allele than of the D allele.
      CONCLUSION: The relationship between ACE genotype and disease in these latter
      groups is still not known, but the present results clearly suggest that ethnic
      origin should be carefully considered in the increasing number of studies on the
      association between I/D ACE genotype and disease aetiology.

PMID- 7814856
TI  - Renovascular resistance in primary hypertension: experimental variations detected
      by means of Doppler ultrasound.
AB  - OBJECTIVE: To gauge the influence of renovascular resistance changes on blood
      flow velocity pulsatility in kidneys of hypertensive patients by means of the
      ultrasonic colour and pulsed-wave Doppler method, since we have previously shown
      in normotensive subjects that the blood flow velocity pulsatility in renal
      interlobar arteries varies with changes in renovascular resistance. METHODS: In
      six male patients with primary hypertension, renal blood flow velocity profiles
      were investigated by means of duplex ultrasound. Single-kidney renovascular
      resistance was assessed by measurements of split renal function (gamma-camera
      renography), renal plasma flow (steady-state para-aminohippurate clearance) and
      cuff blood pressure. The pulsatility index of the blood flow velocity spectrum in
      the renal interlobar artery and renovascular resistance were measured either at
      rest, during infusion of angiotensin II, or after angiotensin converting enzyme
      inhibition. RESULTS: A significant correlation existed between pulsatility index
      and renovascular resistance (r = 0.50, P < 0.002), which did not improve after
      correction for the blood pressure pulsatility. Changes of pulsatility index were
      more closely related (r = 0.64, P < 0.001) to the corresponding changes in
      renovascular resistance. CONCLUSIONS: With the two-dimensional image-guided
      colour and pulsed-wave Doppler method it is possible to assess semiquantitatively
      small intra-individual changes in renovascular resistance in hypertensive
      patients by means of pulsatility index measurements. Pharmacologically induced
      alterations in renovascular haemodynamics may therefore be evaluated with this
      technique.

PMID- 7814857
TI  - On the use of ambulatory blood pressure recordings and insulin sensitivity
      measurements in support of the insulin-hypertension hypothesis.
AB  - OBJECTIVE: To determine the possible correlations between ambulatory blood
      pressure and insulin sensitivity, compared with correlations between office blood
      pressure and insulin. DESIGN: Observational study. SETTING: Policlinic at the
      Department of Geriatrics, Uppsala, Sweden. PATIENTS: Caucasian patients (n = 149)
      of both sexes with untreated essential hypertension. MAIN OUTCOME MEASURES: The
      hyperinsulinaemic euglycaemic clamp and office blood pressure in all subjects. In
      subgroups, also the oral glucose-tolerance test (n = 96) and 24-h ambulatory
      blood pressure (n = 84). RESULTS: Significant correlations were seen between the
      insulin sensitivity index and ambulatory blood pressure recordings, whereas
      fasting plasma insulin levels were uncorrelated with office blood pressure. The
      insulin sum and the 2-h insulin level of the oral glucose-tolerance test were
      more closely correlated with ambulatory blood pressure recordings than was the
      fasting insulin level. In multiple regression analyses the night-time diastolic
      blood pressure showed a significant correlation with the insulin sensitivity
      index even after controlling for the effects of sex, age and body mass index.
      CONCLUSION: The apparent association between blood pressure and insulin
      resistance not only is obscured by measurement error, but is also affected by the
      particular measures of insulin resistance and blood pressure used. The present
      study provides further evidence that a relationship exists between blood pressure
      and hyperinsulinaemia or insulin resistance.

PMID- 7814858
TI  - Serum sodium concentration and risk of stroke in middle-aged males.
AB  - BACKGROUND AND METHODS: Clinical disturbances of the circulating sodium
      concentration are both a cause and a consequence of cerebrovascular disease. We
      examined the relationship between serum sodium level and risk of stroke and major
      ischaemic heart disease in a prospective study of 7690 middle-aged males drawn
      from general practices in 24 British towns followed over a 9.5-year period.
      RESULTS: The mean serum sodium level was 141.5 mmol/l and 375 males on
      antihypertensive treatment were excluded from the analyses. A significant inverse
      trend was seen between serum sodium and risk of stroke up to 144 mmol/l; above
      this the risk of stroke was increased. Those with levels of 143-144 mmol/l showed
      over a 70% reduction in risk of stroke compared with those with levels of < or =
      140 mmol/l. The inverse relationship between sodium and stroke up to 144 mmol/l
      was seen in males with and without pre-existing ischaemic heart disease or
      stroke, in normotensives and untreated hypertensives, and in non-smokers and
      current smokers. A weak but significant inverse association was seen between
      serum sodium and diastolic but not systolic blood pressure. The association
      between serum sodium level and stroke remained significant after adjustment for
      diastolic blood pressure and other factors associated with stroke: age, smoking,
      social class, body mass index, physical activity, heavy drinking, presence of
      diabetes, blood glucose and pre-existing ischaemic heart disease. No association
      was seen between serum sodium level and risk of ischaemic heart disease after
      adjustment for other risk factors. All-cause and non-cardiovascular mortality
      were significantly increased at serum sodium levels of < or = 138 mmol/l,
      probably due to an association between lung cancer and hyponatraemia. CONCLUSION:
      These findings suggest that sodium concentration may be related to risk of stroke
      even at levels of sodium usually regarded as normal.

PMID- 7814859
TI  - Short report: HYPERGENE: a clinical and genetic database for genetic analysis of
      human hypertension.
AB  - OBJECTIVE: Genetic studies of essential human hypertension require the recording
      and management of numerous data concerning multiple hypertensive families. The
      present report describes a new family database, HYPERGENE, and demonstrates its
      potential usefulness in such a complex disease. METHODS: The database was
      implemented on an Apple Macintosh computer using the 4TH DIMENSION software
      program. Through a user-friendly interface, it offers a high-quality data record,
      easy data retrieval and compatibility with other software. PATIENTS: HYPERGENE
      contains a prospective collection of 187 families with at least two hypertensive
      sibs (826 subjects). Each subject was analysed according to the same protocol. To
      allow definition of clinical and biological phenotypes and genetic analysis,
      clinical and biological data were recorded and, at the same time, plasma, urine
      and DNA libraries were stored. RESULTS: Probands were 50.6 years old with an
      early onset (39.1 years of age) of hypertension (157.7/97.8 mmHg); 125 had
      moderate-to-severe hypertension. According to our selection criteria, only one
      out of 187 sibships had familial dislipidaemic hypertension. Of the living
      fathers, 45% were examined, and 54% of the living mothers: 48.6% had an onset of
      hypertension before age 50 years. Children (mean age 28.7 years) of hypertensive
      sibs presented a high percentage of hypertension (8.3%). CONCLUSION: The
      HYPERGENE database facilitates data storage and analysis on familial
      hypertension, and should prove a useful tool for assessing molecular biology
      results in the field of hypertension and for allowing collaborative research.

PMID- 7814860
TI  - Is blood pressure treatment as effective in a population setting as in controlled
      risk? Results from a prospective study.

PMID- 7814861
TI  - IL-15 has stimulatory activity for the induction of B cell proliferation and
      differentiation.
AB  - The identification and cloning of the novel cytokine IL-15 were recently
      described. IL-15 is produced by a wide range of cell types, with the highest
      levels of IL-15 mRNA being detected in epithelial lines, monocytes, muscle, and
      placenta. Although it has no sequence identity with IL-2, IL-15 shares many of
      the T cell-stimulatory activities described for IL-2. We have examined IL-15 for
      its ability to stimulate B cells and have compared its activity with that of IL
      2. IL-15 costimulates proliferation of B cells activated with immobilized anti
      human IgM or phorbol ester, but has no stimulatory effect on resting B cells. In
      combination with recombinant CD40L, IL-15 is a potent inducer of polyclonal IgM,
      IgG1, and IgA secretion, but does not cause production of IgG4 or IgE. The
      activity of IL-15 in B cell proliferation and differentiation assays is
      comparable with that of IL-2. Studies that used neutralizing Abs have
      demonstrated that, for signal transduction in B cells, IL-15 uses the beta-chain
      of the IL-2R complex but, unlike IL-2, does not require the alpha-chain. IL-2 is
      required for the generation of a human primary Ag-specific in vitro response
      using sheep erythrocytes as Ag. Of all cytokines examined, only IL-15 has the
      capacity to replace IL-2 in this system, although only partially. In summary, IL
      15 has comparable activity with IL-2 for the induction of B cell proliferation
      and differentiation and uses at least some of the components of the IL-2R complex
      to mediate its effects.

PMID- 7814862
TI  - Ligand binding to Fc gamma R induces c-myc-dependent apoptosis in IL-2-stimulated
      NK cells.
AB  - The role of signals transduced via Fc gamma RIIIA in the modulation of the
      proliferative potential of NK cells has been investigated. Fc gamma R stimulation
      does not induce NK cell proliferation, and inhibits that induced by IL-2, but not
      by IL-12, as measured by [3H]TdR incorporation, without affecting entrance or
      progression through cell cycle. The inhibitory effect depends, at least in part,
      on induced apoptosis of the cells, detected by both light and electron microscopy
      examination. Fc gamma R stimulation induces apoptosis only in NK cells that have
      been previously activated by IL-2: this occurs within 3 h from receptor
      stimulation and is independent from de novo receptor-induced RNA or protein
      synthesis, but requires receptor-induced activation of protein tyrosine kinases
      and extracellular Ca2+ influx. IL-2 induces accumulation of c-myc mRNA in NK
      cells, and treatment of the cells with c-myc antisense oligodeoxyribonucleotides
      during the IL-2 stimulation phase inhibits the susceptibility to Fc gamma RIIIA
      induced cell death, indicating that the induction of sustained levels of this
      proto-oncogene is necessary for the phenomenon. Thus, a two-step model is
      suggested for the Fc gamma R-induced apoptosis in IL-2 activated NK cells: the
      first step involves induced expression of c-myc, and possibly other permissive
      factors, upon IL-2 prestimulation; the second depends directly on the stimulation
      of the receptor, independently of additional gene induction. The evidence
      presented here suggests a mechanism of control of NK cell expansion at the latest
      stages of Ab-dependent immune responses.

PMID- 7814863
TI  - Alpha 3 beta 1 and alpha 6 beta 1 integrins mediate laminin/merosin binding and
      function as costimulatory molecules for human thymocyte proliferation.
AB  - Integrins comprise a superfamily of alpha beta heterodimers that serve as cell
      signaling as well as adhesion molecules. We demonstrate that the alpha 3 beta 1
      and alpha 6 beta 1 integrins are laminin/merosin receptors expressed in human
      thymocytes. By reverse transcriptase-PCR analysis, we determined that the alpha
      3A beta 1, but not the alpha 3B beta 1, cytoplasmic structural variant of alpha 3
      beta 1 is expressed in thymocytes. In contrast, both alpha 6A beta 1 and alpha 6B
      beta 1 cytoplasmic structural variants of alpha 6 beta 1 are expressed. A small
      percentage (10 to 15%) of human thymocytes bind to immobilized laminin, and even
      fewer (3 to 5%) bind to merosin, the laminin isoform normally present in the
      thymus. This binding, however, can be increased to 39 to 41% after activation of
      thymocytes with Mn2+ (or PMA). Binding to either laminin or merosin is completely
      inhibited by anti-beta 1 mAb or by a mixture of anti-alpha 3 and anti-alpha 6
      mAbs, indicating that both alpha 3 beta 1 and alpha 6 beta 1 participate in
      thymocyte adhesion to the laminin family of extracellular matrix proteins. The
      protein kinase C inhibitors, calphostin C and staurosporine, inhibit Mn(2+)
      enhanced thymocyte binding, suggesting that protein kinase C activity is crucial
      for the binding. Furthermore, the data indicate that at least two divalent cation
      binding sites serve to regulate integrin binding activity. Finally, we show that
      both immobilized laminin and merosin have costimulatory function for anti-CD3
      induced thymocyte proliferation, and both anti-alpha 3 and anti-alpha 6 mAbs can
      block this proliferative response. The cooperative function of alpha 3 beta 1 and
      alpha 6 beta 1 evidenced in the laminin/merosin binding and proliferation assays
      suggests that thymocyte-merosin interactions may play an important role in thymic
      T cell development.

PMID- 7814864
TI  - Presentation of endogenous and exogenous antigens is not affected by inactivation
      of E1 ubiquitin-activating enzyme in temperature-sensitive cell lines.
AB  - Little is known regarding the mechanism by which MHC class I-associated peptides
      are generated. Proteins can be targeted for degradation by the covalent
      attachment of ubiquitin. The first step in ubiquitin conjugation to proteins is
      its binding to E1 ubiquitin-activating enzyme. To study the role of ubiquitin
      targeted protein degradation in Ag processing, we used two mutant cell lines with
      temperature-sensitive E1 proteins, and a recombinant vaccinia virus expressing
      wild-type human E1. One of the cell lines examined (hamster ts20 cells) was
      previously reported to have a minimal capacity after a 1-h incubation at 41
      degrees C to present osmotically loaded OVA to a T cell hybridoma, as assessed by
      IL-2 release. Even after incubating the same cells for 1 h at 43 degrees C, we
      failed to detect an E1-related decrease in the presentation of biosynthesized or
      osmotically loaded OVA to splenic T cells, as measured by target cell lysis. We
      introduce the use of mouse tsA1S9 cells to Ag-processing studies and provide the
      initial biochemical characterization of their defect in protein ubiquitination.
      Relative to parental L929 cells, after thermal inactivation of E1, these cells
      actually demonstrate enhanced presentation of endogenous or exogenous viral Ags
      to T cells. Our findings do not support a role for protein ubiquitination in Ag
      processing, and indicate that either the temperature-sensitive cell lines
      examined do not exhibit a sufficient reduction in ubiquitin-conjugating activity
      to affect the generation of antigenic peptides, or that ubiquitin-targeted
      proteolysis is not essential for processing the two exogenous and six endogenous
      Ags examined.

PMID- 7814865
TI  - Nonresponders to hepatitis B vaccine can present envelope particles to T
      lymphocytes.
AB  - The mechanisms causing nonresponsiveness to hepatitis B surface Ag (HBsAg)
      vaccines in humans remain largely unknown. The increased incidence of
      nonresponsiveness in subjects with HLA-DR3 or -DR7 haplotype suggests that immune
      response mechanisms governed by genes of the MHC are involved. It is conceivable
      that APC of nonresponders are defective in the presentation of HBsAg because they
      are unable to adequately take up, process, or present this Ag. To examine this
      hypothesis we have used PBMC from nonresponders to present recombinant particles
      containing S or PreS2-S sequences to HBsAg-specific T cell lines from haplo
      identical responder vaccinees. The proliferative response of these lines was used
      to evaluate the efficacy of Ag presentation. Unfractionated PBMC from five DR2+
      and six DR7+ nonresponders did not proliferate to HBsAg in vitro, whereas they
      vigorously proliferated upon stimulation with tetanus toxoid, thus ruling out the
      presence of a generalized immunodeficiency. All DR2(15)+ nonresponders were able
      to present hepatitis B envelope Ag to HBsAg-specific, DR1501-restricted T cells.
      PBMC from six DR7+ nonresponders were all able to present HBsAg to DR07
      restricted T cell lines and PBMC from three DPw4+ nonresponders were able to
      present HBsAg to DP0402-restricted T cell lines. Additional experiments showed
      that PBMC from two nonresponders presented HBsAg equally well and sometimes
      better than PBMC from two partially HLA-matched high responders. We conclude that
      HLA-DR2+, -DR7+, and -DPw4+ nonresponder vaccinees are able to take up, process
      and present HBsAg to allogeneic, haplo-identical T cell lines in vitro.

PMID- 7814866
TI  - Selective processing of exogenous antigens by antigen-presenting cells with
      deleted MHC genes.
AB  - Recently, APCs expressing genes for the alpha- and beta-chains of MHC class II,
      but not other proteins encoded in the MHC class II locus, have been found to be
      defective in processing proteins by the MHC class II Ag presentation pathway. Ag
      presentation of hen egg OVA has been examined in one of these cell lines, T2.Ak.
      OVA was processed normally by T2.Ak when compared with OVA processed by T1.Ak, a
      cell line that expresses the MHC genes missing in T2.Ak. By contrast, native hen
      egg lysozyme (HEL) was not presented as Ag by T2.Ak, which is in agreement with
      earlier results. Digestion with thiol proteases is important for Ag processing of
      HEL. We therefore analyzed the expression of these enzymes in T1.Ak and T2.Ak by
      using a reagent that specifically radiolabels thiol proteases. In these
      experiments, the repertoire of proteases expressed in the microsomes of T1.Ak was
      found to be distinct from the repertoire expressed by T2.Ak. Finally, in in vitro
      digestion experiments, the group of thiol proteases active in T1.Ak microsomes
      digested HEL differently from the group identified in T2.Ak. These results
      provide evidence that the defect in Ag presentation that is encoded by MHC genes
      and manifests itself in defective processing of HEL is not absolute. Further, the
      mutation in T2.Ak coincides with altered activities of thiol proteases, a class
      of enzymes involved in processing exogenous Ags.

PMID- 7814867
TI  - Constitutive presentation of dominant epitopes from endogenous naturally
      processed self-beta 2-microglobulin to class II-restricted T cells leads to self
      tolerance.
AB  - The mouse beta 2-microglobulin (m beta 2-m) peptide corresponding to residues 25
      40 binds to the MHC class II molecules I-Ad and I-Ed and is immunogenic in BALB/c
      beta 2-m-deficient but not in normal BALB/c mice. The self-m beta 2-m peptide 25
      40 is presented by both I-Ad and I-Ed class II molecules as demonstrated by the
      activation of T cell hybridomas specific for this sequence obtained from beta 2-m
      knock-out mice. By analyzing the effect of N- and C-terminal truncations of m
      beta 2-m25-40 on binding to class II molecules and on activation of T cell
      hybridomas, the minimum epitopes recognized by I-Ad and I-Ed-restricted T cells
      are included within amino acid residues 26-39 and 24-36, respectively. Both sets
      of T hybridomas are also activated by the corresponding naturally processed self
      epitope presented by APC from BALB/c mice and from other H-2d strains,
      irrespective of their Mls phenotype. Therefore, the sequence 25-40 contains
      dominant naturally processed self-epitopes of the mouse beta 2-m. Processing of
      endogenous m beta 2-m is sensitive to protease inhibitors and lysosomotropic
      amines, and is not caused by reuptake of shed or released protein. These results
      indicate that self-beta 2-m-peptide-MHC class II complexes derive from
      constitutive processing of the endogenous intracellular pool of m beta 2-m in an
      acidic endosomal compartment. Antigenic complexes between m beta 2-m peptides and
      I-Ad or I-Ed class II molecules are constitutively expressed by APC of different
      tissues, including the thymus, and they are able to induce T cell tolerance, as
      shown by the lack of T cell response to m beta 2-m25-40 in BALB/c mice.

PMID- 7814868
TI  - Variations in the number of peptide-MHC class I complexes required to activate
      cytotoxic T cell responses.
AB  - We determined equilibrium constants for the binding of 16 peptides (based on four
      T cell epitopes) to three MHC class I proteins (A2, Kb, and Ld) on intact cells
      and estimated the number of accessible peptide-binding sites on these cells. From
      these results, and the concentrations of peptides required to sensitize target
      cells for lysis by CD8+ CTL, we conclude that the critical number of peptide-MHC
      complexes required per target cell for the activation of CTL responses varies
      with different combinations of peptide-MHC complexes and CTL clones from several
      thousand complexes to fewer than ten per target cell.

PMID- 7814869
TI  - Murine T and B cell responses to natural and recombinant hornet venom allergen
      Dol m 5.02 and its recombinant fragments.
AB  - White-face hornet venom allergen, Dol m 5.02, is a protein of 204 amino acid
      residues. This protein and its overlapping fragments, of 53-114 residues in size,
      containing the N-terminal, middle, and C-terminal regions of the molecule, can be
      expressed in high yield in bacteria by using the plasmid vector pQE12. Natural
      (n) and recombinant (r) Dol m 5.02s and the r-fragments are about equally
      immunogenic for IgG Ab response in BALB/c mice. n-Dol m 5.02 induces mainly
      murine IgG Abs specific for its discontinuous B cell epitopes and, to a lesser
      extent, Abs specific for its continuous epitopes. r-Dol m 5.02 and the r
      fragments induce only Abs specific for continuous B cell epitopes that are common
      with those of the n-protein. Abs specific for the discontinuous epitopes show
      higher affinity than those specific for the continuous epitopes. r-Dol m 5.02 and
      the r-fragments are as efficient as n-Dol m 5.02 in inducing murine T cell
      responses specific for the n-protein. The differences in the immunogenicity of n-
      and r-proteins or r-peptide fragments for B and T cell responses are related to
      their conformations, inasmuch as only the n-protein is cross-linked by four
      disulfide bonds. These findings are relevant to the potential use of r-fragments
      as immunotherapeutic reagents in humans.

PMID- 7814870
TI  - The role of MHC class I molecules in the generation of endogenous peptide/MHC
      complexes.
AB  - Cellular proteins undergo proteolysis to yield peptide/MHC class I complexes for
      display on the APC surface. During this process it is not clear whether MHC
      molecules bind to and stabilize independently generated peptides, or whether they
      are involved in the peptide cleavage events. In this study, we analyzed the role
      of MHC molecules in Ag processing by characterizing the naturally processed
      peptide analogues of OVA (OVA257-264, SL8) in APC. DNA constructs encoding SL8
      precursors were transfected into cells that varied in their MHC expression. By
      HPLC fractionation of cell extracts and with sensitive T cell assays for both the
      processed SL8 and its minimal Met-SL8 (MSL8) precursor, we determined that
      expression of Kb MHC molecule was essential for detecting processed peptides in
      living cells. Curiously, although the translated MSL8 nonapeptide precursor
      itself could bind Kb as well as the SL8 octapeptide, and MSL8 was available to
      MHC, only the SL8 peptide was found in Kb cell extracts. The presence of
      naturally processed SL8, but not MSL8 peptide in Kb-expressing cells suggests
      that the precise identity of endogenously processed peptides is also strongly
      influenced by the MHC molecules.

PMID- 7814871
TI  - TGF-beta suppression of IFN-gamma-induced class II MHC gene expression does not
      involve inhibition of phosphorylation of JAK1, JAK2, or signal transducers and
      activators of transcription, or modification of IFN-gamma enhanced factor X
      expression.
AB  - TGF-beta is a widely expressed immunoregulatory protein that exerts a diverse
      range of effects on many types of cells. One of the effects of TGF-beta is the
      inhibition of both constitutive and cytokine-inducible class II MHC gene
      expression. In this study, we demonstrate that TGF-beta inhibits expression of
      class II MHC surface protein, mRNA, and promoter activity in primary astrocytes,
      and that this inhibition is both dose and time dependent. TGF-beta does not act
      to inhibit IFN-gamma-induced gene expression in a global fashion, as induction of
      ICAM-1 and IRF-1 gene expression by IFN-gamma is unaffected by treatment with TGF
      beta. Furthermore, TGF-beta does not affect events that are involved in IFN-gamma
      induced intracellular signaling such as tyrosine phosphorylation of JAK1, JAK2,
      and STAT1 alpha, nor does it affect IFN-gamma induction of the class II X2 box
      binding protein IFN-gamma enhanced factor X. We speculate that TGF-beta may be
      exerting its effects by modulating the expression or function of constitutively
      expressed factors responsible for regulation of class II MHC gene expression in
      astrocytes.

PMID- 7814872
TI  - Characterization of donor chimerism, alloreactive host T cells and memory cell
      development in thymi from mice resistant to neonatal transplantation tolerance.
AB  - Certain B10 background mouse strains are resistant to tolerance induction after
      neonatal inoculation of class I/II MHC-disparate F1 hybrid cells. Despite initial
      thymic deletion of alloreactive cells, the majority (95%) of these mice reacquire
      the capacity to reject donor allografts. These current studies examined thymi of
      adult B10.S (H-2S/H-2E-) mice that neonatally received (B10.S x B10.A)F1 cells,
      before and after rejection or acceptance of B10.A (H-2k/d/H-2E+) skin grafts.
      Alloreactive thymic V beta 11+ and V beta 5+ T cells were often reduced in the
      injected recipients preceding allograft challenge. In some mice a single B10.A
      skin graft generated an increase in these T cell populations concurrent with
      allograft rejection. Injected mice that accepted B10.A skin grafts (i.e.,
      tolerant) or that rejected two sequential B10.A grafts often had a reduction of
      these T cells. Thymic memory cells (CD44high+) were present before transplant in
      injected mice and reduced in the tolerant mice. Donor chimeric cells were
      identified in the majority of injected mice before transplant and diminished
      after B10.A graft application. A greater proportion of chimeric cells coexpressed
      CD11b or B220 in the tolerant mice. Thus, neonatally injected B10.S mice
      resistant to tolerance induction reacquire immunocompetent thymic T cells bearing
      characteristics of memory T cells that could mediate graft rejection. Finally,
      the initial presentation of chimeric cells (e.g., macrophages) that may
      efficiently present class I Ags through H-2E likely increases the possibility of
      adult tolerance.

PMID- 7814873
TI  - CD45-cross-linking stimulates IFN-gamma production in NK cells.
AB  - The in vitro demonstration of the ability of NK cells to secrete cytokines
      prompted in vivo studies that illustrated the importance of NK cell-derived
      cytokines in regulating immune responses. Cross-linking of CD16 on NK cells can
      stimulate cytokine production. CD16-independent interactions capable of
      stimulating cytokine production have also been described, but molecules mediating
      such stimulations remain to be biochemically defined. We report here that cross
      linking of CD45 specifically stimulates IFN-gamma production in human NK cells.
      The NK cells used were IL-2-activated adherent NK cells and from the NK3.3 cell
      line. The ability of CD45 mAbs to stimulate NK cells appears not to be dependent
      on CD16, as CD45 mAbs of both IgG1 and IgG2a isotypes were equally stimulatory,
      as were F(ab')2 compared with whole anti-CD45 mAbs. Resting NK cells, like T
      cells, express predominantly CD45RA, whereas IL-2 activated adherent NK cells
      acquire expression of CD45RO. Abs specific for CD45RO, but not CD45RA, were able
      to stimulate IFN-gamma production in NK cells. It has been reported that one
      ligand for CD45RO is CD22 beta. We tested the ability of CD22-expressing
      transfectants to bind to and stimulate NK cells. Whereas NK cells bound to CD22
      alpha and CD22 beta transfectants, this interaction was not inhibited by CD45RO
      Abs. In addition, neither of the CD22-transfectants were able to stimulate NK3.3
      cells to secrete IFN-gamma. These observations collectively suggest that binding
      of NK3.3 cells to CD22 may be independent of CD45RO on NK3.3 cells.

PMID- 7814874
TI  - Oligomeric IgD augments and monomeric IgD inhibits the generation of IgG memory
      antibody responses in normal, but not in IgD-deficient, mice.
AB  - Dimeric or aggregated IgD causes augmentation of primary and secondary Ab
      responses in mice when injected a few days before or together with the primary
      dose of Ag. This effect is mediated by Th cells and seems to be linked to the up
      regulation of receptors for IgD on CD4+ T cells. IgD-R cross-linking is needed
      for receptor up-regulation. Here we show that addition of monomeric IgD to
      dimeric or aggregated IgD blocks IgD-R up-regulation on T cells in vitro and in
      vivo, as well as their immunoaugmenting effect in vivo. More importantly,
      monomeric IgD injected 6 to 24 h before a primary Ag injection also inhibits 1)
      the up-regulation of IgD-R on T cells induced by Ag injection alone, and 2) the
      generation of IgG memory, as shown in the response to a second dose of Ag
      injected on day 10. These results suggest that IgD-R on T cells contribute to the
      T-B cell interaction involved in the priming for a secondary response. The
      augmenting effect of oligomeric IgD and the inhibiting effect of monomeric IgD on
      secondary Ab responses are not observed in IgD-/- (IgD-deficient) mice, although
      injection of oligomeric IgD leads to IgD-R up-regulation on T cells in these
      mice. These results indicate that IgD presented in the form of immune complexes,
      most likely on the surface of B cells, is a prerequisite for the immunoaugmenting
      effects exerted by IgD-R+ T cells. Thus, IgD is the only physiologic ligand for
      IgD-R on T cells.

PMID- 7814875
TI  - Diversity of V gamma gene segments rearranged to the J gamma 4 gene in mice.
AB  - Because there are limited numbers of V gamma gene segments and most V gamma
      rearrangements occur within clusters of the J gamma-C gamma genes in mice, gamma
      chains display limited diversity compared with other TCR chains. In this study,
      we examined the nucleotide sequences of the V gamma-J gamma genes expressed in
      the gamma delta T cells appearing at the inflamed sites after Salmonella
      infection in DBA/2 mice. Most of the productive gamma gene rearrangements were V
      gamma 1-J gamma 4, whereas V gamma 2 and a unique V gamma, the 5' region of which
      was identical with sequences of the V gamma 2 gene, and the 3' region of which
      was identical with that of the V gamma 1 gene, were found to be rearranged to J
      gamma 4 gene, albeit at low frequency. Analysis of the ontogenic appearance of
      the rearrangements in the J gamma 4-C gamma 4 locus revealed that V gamma 2-J
      gamma 4 gene rearrangement was frequent in fetal thymocytes at the early stage of
      gestation. Most of the early fetal V gamma 2-J gamma 4 rearrangements exhibited
      the identical junction, a nonfunctional canonical sequence. The sequence analysis
      of the coding joint and the reciprocal recombination signal joint suggests that
      short homology-mediated direct recombination and chromosomal inversion mechanism
      are involved in fetal V gamma 2-J gamma 4 gene rearrangement. Taken together, our
      data suggest that the recombination of multiple V gamma segments with J gamma 4
      can diversify the V gamma repertoire.

PMID- 7814876
TI  - Cis-acting DNA elements of mouse granulocyte-macrophage colony-stimulating factor
      gene responsive to Fc epsilon receptor cross-linking stimulation in the mouse
      mast cell line MC/9.
AB  - Mouse mast cells produce many kinds of cytokines in response to cross-linking of
      high affinity Fc epsilon receptor (Fc epsilon RI). Among these cytokines,
      granulocyte-macrophage CSF (GM-CSF) gene induction in mouse mast cells has been
      reported to be regulated at both the transcriptional level and the post
      transcriptional level. We analyzed the mechanism of the transcriptional
      regulation of GM-CSF gene induction through Fc epsilon RI cross-linking
      stimulation in the mouse mast cell line MC/9. In MC/9, the GM-CSF gene was
      activated transcriptionally by Fc epsilon RI cross-linking stimulation. The 5'
      deletion analysis of GM-CSF gene promoter indicated that the 5' boundary of the
      responsive promoter region lay between positions -113 and -95. When the deletion
      was extended to positions -72 or -60, the stimulatory effect was significantly
      diminished. We then examined 3' deletion of pmGMCAT -113 from position -60. This
      analysis indicated that the 3' boundary lay between positions -84 and -72. No
      subfragments of the region spanning positions -113 to -72 could cover the full
      induction level. A site-directed mutagenesis experiment revealed that the
      sequence spanning positions -108 to -72 was needed for full activation. These
      data indicate that GM-CSF gene in mast cells is activated mainly through the
      sequence spanning positions -108 to -72.

PMID- 7814877
TI  - A cDNA clone coding for a novel allergen, Cla h III, of Cladosporium herbarum
      identified as a ribosomal P2 protein.
AB  - Mold allergens represent a major cause of atopic disorders. Progress in the
      molecular characterization of allergens has been hampered by batch-to-batch
      variation and poor yields in mold extracts. In the present study, we established
      a cDNA library in lambda ZAP II by using mRNA isolated from a major allergen
      producing mold, Cladosporium herbarum. From this library, a novel allergen has
      been cloned and sequenced. The clone encodes a full length protein of 111 amino
      acids with a molecular mass of 11.1 kDa and pI of 3.94. By using sequence
      homology analysis, the allergen was found to belong to the ribosomal P2 protein
      family. Approximately 60% peptide sequence homology was found between the cloned
      protein and other known fungal ribosomal P2 proteins. In addition to conserved C
      terminal sequences and serine blocks for phosphorylation in all eukaryotic
      ribosomal P2 proteins, this protein also contains a potential N-glycosylation
      site at position 15-17. Northern blots demonstrated that mRNA molecules of this
      gene are present even at late stages of culture. The gene was expressed in
      Escherichia coli by using the pMAL-2c system, and murine antisera against the
      recombinant allergen (rCh2.1) were generated. The antisera revealed that the
      native allergen corresponding to rCh2.1 was present in extracts prepared by
      grinding mycelia under liquid nitrogen in the presence of protease inhibitors,
      but absent in extracts prepared by conventional methods. This result indicates
      the usefulness of recombinant allergens in characterization and standardization
      of mold allergenic extracts.

PMID- 7814878
TI  - Lymphokine mRNA expression by transplantable murine B lymphocytic malignancies.
      Tumor-derived IL-10 as a possible mechanism for modulating the anti-tumor
      response.
AB  - In vitro and in vivo expressions of cytokine mRNAs by four transplantable murine
      B lymphocytic malignancies designated A20, MOPC 315, 2PK-3, and RAW 8.1 were
      determined using sensitive reverse-transcribed (RT)-PCR. Despite significant
      differences in both the stage of B cell differentiation represented by each cell
      line and the method used to induce the original B lymphocytic tumors, IL-6 and IL
      10 mRNAs were detected in each of the cultured cell lines. Whereas IL-2, IL-4, IL
      5, and IL-12 mRNAs were not detected in cultured cells, expression of cytokine
      mRNAs in solid tumor tissue was quite different. RT-PCR of poly(A)+ RNA isolated
      from each of the four solid tumors demonstrated the presence of IL-4, IL-5, IL-6,
      IL-10, TGF-beta 1, and TNF-alpha mRNAs. There was a noticeable lack of
      significant IL-2 mRNA expression in any of the solid tumors. Using RT-PCR, it was
      clear that each of the malignant B lymphocytes expressed IL-6, IL-10, TGF-beta 1,
      and TNF-alpha, with limited expression of IL-4 and IL-5. To explore the
      mechanisms that might contribute to the lack of IL-2 mRNA in these solid tumors,
      quantitative competitive (QC)-RT-PCR was used to quantify expression of IL-10
      mRNA. MOPC 315 tumor expressed the most IL-10 mRNA (23.2 pg/micrograms of
      poly(A)+ RNA), whereas 2PK-3, A20, and RAW 8.1 tumors expressed 7.4, 2.6, and 0.6
      pg/micrograms of poly(A)+ RNA, respectively. Secretion of IL-10 into culture
      supernatants or into sera and ascitic fluid of tumor-bearing animals correlated
      with mRNA expression. This dysregulated IL-10 production in animals with B
      lymphocytic tumors suggested a mechanism that may account for the lack of IL-2
      mRNA expression in solid tumors, and suggested a possible mechanism by which
      malignant B lymphocytes may limit cell-mediated antitumor responses.

PMID- 7814879
TI  - Melanoma patients immunized with melanoma cell vaccine induce antibody responses
      to recombinant MAGE-1 antigen.
AB  - The MAGE-1 gene was recently characterized to encode an immunogenic tumor Ag on
      several types of human tumors, including melanoma. This Ag is expressed in a wide
      variety of human tumors and not in normal cells, except testicular tissue, as
      assessed through specific mRNA analysis. In this study we cloned the MAGE-1 gene
      exon 3 region from a colon carcinoma cell line and expressed it in Escherichia
      coli. The recombinant MAGE-1 protein was affinity purified. By using Western blot
      analysis, IgG and IgM anti-MAGE-1 Abs were detected in the sera of melanoma
      patients. Fifty-three patients immunized with a melanoma cell vaccine (MCV) were
      assessed for anti-MAGE-1 IgG responses by using a MAGE-1 Ag-specific ELISA. The
      MCV consisted of three melanoma cell lines that expressed MAGE-1. Comparisons of
      anti-MAGE-1 IgG response pre-MCV treatment with 12- to 16-wk post-MCV treatment
      were made. Fifty-seven percent of the patients immunized with the MCV showed
      significant enhancement of IgG response to recombinant MAGE-1 protein. Patients
      who responded had no particular HLA-A or -B allele expression pattern. Melanoma
      patients immunized with whole cell MCV containing MAGE-1 can enhance anti-MAGE-1
      IgG Abs. Recombinant MAGE-1 protein can be used to assess patient response to
      MAGE-1 and will be investigated as a potential cancer vaccine against a wide
      variety of human tumors that express MAGE-1.

PMID- 7814880
TI  - Fibrosarcoma cells expressing allogeneic MHC Class II antigens induce protective
      antitumor immunity.
AB  - The initiation of effective immune responses usually requires presentation of Ags
      by MHC class I and class II molecules. Although most tumors express MHC class I
      molecules, MHC class II molecule expression is generally limited to specialized
      APCs. One reason spontaneous tumors may fail to elicit effective immune responses
      is that tumor Ags are inefficiently presented by APCs, and adequate T cell
      mediated help is not generated. To test this hypothesis, we investigated the
      possibility of enhancing Th cell stimulation by inducing expression of MHC class
      II molecules on tumor cells. We transfected a murine fibrosarcoma, Sa1N, with the
      genes encoding allogeneic (I-Ad) or syngeneic (I-Ak) MHC class II molecules. We
      then compared the tumorigenic and immunogeneic potential of these transfectants
      to parental Sa1N tumor cells. Subcutaneous injection of allogeneic or syngeneic
      transfectants resulted in dramatically fewer tumors than injection of unmodified
      fibrosarcoma cells, and mice inoculated with MHC class II gene-transfected cells
      were resistant to subsequent challenge with parental Sa1N cells. Rejection of
      allogeneic MHC class II Ag+ tumor cells could be mediated by either CD4+ or CD8+
      T cells, whereas rejection of secondary challenge with wild-type Sa1N tumor cells
      required both T cell subsets. These results demonstrate that allogeneic, as well
      as syngeneic, MHC class II Ag+ tumor cells can stimulate protective antitumor
      immunity.

PMID- 7814881
TI  - Activation-induced CD4+ T cell death by apoptosis in experimental Chagas'
      disease.
AB  - Infection of mice with Trypanosoma cruzi, the causative protozoan agent of human
      Chagas' disease, leads to immunosuppression of the T cell compartment and to
      chronic cardiac inflammation which resembles the human infection. Recently,
      reinduction of programmed cell death by apoptosis in mature T cells has been
      demonstrated. It has been suggested that mature T cell apoptosis could play a
      role in immunosuppression caused by virus infection. In this report, we have
      investigated the occurrence of mature T cell apoptosis in murine experimental
      Chagas' disease. Infection with T. cruzi metacyclic forms led to a relative
      accumulation of CD8 T cells over CD4 T cells in the spleens of infected mice.
      Splenic T cells from T. cruzi-infected donors, but not from control littermates,
      died in vitro upon stimulation with T cell mitogens Con A and anti-TCR-alpha beta
      mAb in a dose-dependent fashion. DNA fragmentation into nucleosome-sized bands
      was detected in the supernatants of CD4+ T cells from infected origin, after
      stimulation with the T cell mitogen Con A. Upon in vitro stimulation with either
      anti-TCR-alpha beta or Con A, CD4+ T cells were susceptible to elimination,
      whereas CD8+ T cells were not. Splenic T cells from infected donors were markedly
      unresponsive to anti-TCR mAb in proliferative assays and underwent apoptosis in
      vitro, as assessed by electron microscopy. Apoptosis also occurred in vivo in the
      course of acute infection, as seen by DNA fragmentation in freshly explanted
      splenic cells and purified T cell subsets. The data indicate that activation
      induced CD4+ T cell death by apoptosis is a prominent feature of experimental
      infection with T. cruzi, and could play a role in immunosuppression and parasite
      persistence in infected hosts.

PMID- 7814882
TI  - Generation of tumor-specific CTLs from melanoma patients by using peripheral
      blood stimulated with allogeneic melanoma tumor cell lines. Fine specificity and
      MART-1 melanoma antigen recognition.
AB  - PBLs were isolated from 13 patients with metastatic melanoma. Mixed lymphocyte
      tumor cell cultures (ML TCs) were established (15 times) by using irradiated HLA
      matched (one class I locus) allogeneic melanoma tumor cell lines (13 times) or
      autologous melanoma tumor cell lines (two times) in medium containing 120 IU/ml
      IL-2 and 100 IU/ml IL-4. PBLs grew to levels that could be assessed for
      functional reactivity 9 of 15 times. In seven of nine cases, CD3+CD8+ CTLs grew
      from MLTCs that were tumor specific; five were restricted by HLA-A2 and two were
      restricted by HLA-A24. Four of the tumor-specific CTL lines lysed autologous
      fresh tumor cells. Tumor-specific CTLs from two of three patients had cytolytic
      activity identical with tumor-infiltrating lymphocytes (TIL) derived from tumor
      biopsies removed earlier and grown in high concentrations (6000 IU/ml) of IL-2.
      Three of the HLA-A2-restricted tumor-specific CTLs were shown to recognize 293
      cells transfected with HLA-A2.1 cDNA and the gene encoding the melanoma Ag, MART
      1. In addition, these CTLs recognized the T2 cell line pulsed exogenously with
      the peptide MART-1(27-35), which is the nine-amino acid immunodominant epitope of
      the MART-1 Ag recognized on melanoma tumor cells by nearly all HLA-A2-restricted
      TIL. Thus, we have demonstrated the ability to generate tumor-specific CTLs from
      PBLs that are similar in their reactivity to TIL. This technique obviates the
      need for autologous tumor tissue and suggests that PBLs contain sufficient CTL
      precursors for use in generating antitumor CTLs for cellular immunotherapy
      trials.

PMID- 7814883
TI  - Reactivity of autologous CD4+ T lymphocytes against human melanoma. Evidence for
      a shared melanoma antigen presented by HLA-DR15.
AB  - Reactivity of CD8+ T lymphocytes against human melanoma has been extensively
      characterized, but little is known about melanoma Ags recognized by CD4+
      lymphocytes. We have identified CD4+ CTL that recognize shared melanoma Ag(s)
      expressed by autologous melanoma cells and a subset of allogeneic melanomas. The
      same Ag(s) was shared by autologous and positive allogeneic melanomas by cross
      blocking experiments. Cytotoxicity was directed against epitopes presented by HLA
      DR on target melanoma cells, and allelic typing revealed that cytotoxicity was
      restricted through HLA-DR15. These CD4+ T cells released IFN-gamma, IL-4, and TNF
      alpha, but not IL-2, in response to HLA-DR15+ target cells. CD4+ T cells did not
      lyse DR15+ nonmelanoma cell types, including melanocytes or fibroblasts (induced
      to express HLA-DR by IFN-gamma). Thus, by cytotoxicity assays, shared Ags were
      only recognized on melanoma cells but not on normal melanocytes. In summary, this
      analysis shows that melanoma cells share an Ag that is presented by HLA-DR15.

PMID- 7814885
TI  - Synthetic hexa- and heptapeptides that inhibit IL-8 from binding to and
      activating human blood neutrophils.
AB  - IL-8 is a member of the chemokine alpha subfamily that activates and is
      chemotactic for neutrophils. In these studies, we have synthesized and
      characterized a hexapeptide inhibitor of IL-8. This peptide, with an acetylated
      amino terminus and an amidated carboxyl terminus (Ac-RRWWCR-NH2), inhibited the
      specific binding of 125I-IL-8 to neutrophils. The inhibition was biphasic and
      apparent Ki was estimated to be approximately 2.7 microM and 13 microM for two
      different IL-8 binding sites. The peptide inhibited neutrophil chemotaxis, beta
      glucuronidase release from neutrophils, and rabbit skin edema induced by IL-8
      with an EC50 of 90 microM, 0.8 microM, respectively. Ac-RRWWCR-NH2 also
      suppressed the binding of macrophage inflammatory protein (MIP) 2 beta to
      neutrophils. However, it did not inhibit the binding of MIP-1 alpha, C5a, or
      leukotriene B4 to neutrophils, chemotaxis induced by FMLP, or beta-glucuronidase
      release induced by FMLP, C5a, or leukotriene B4. Additional peptides were
      analyzed to identify a better inhibitor. Inhibition of binding by Ac-rrwwcrc-NH2
      synthesized with all D-amino acids was almost four times more potent than Ac
      RRWWCR-NH2. Small peptide homologues of the amino-terminal end of IL-8 failed to
      inhibit IL-8 binding to neutrophils. These studies have identified several
      peptides that significantly inhibit IL-8 function. Because IL-8 seems to be an
      important inflammatory mediator of several human illnesses, these peptides may
      have pharmacologic potential.

PMID- 7814884
TI  - Mechanisms underlying acute mast cell-induced leukocyte rolling and adhesion in
      vivo.
AB  - It has been proposed that a primary detector mechanism for tissue infection or
      injury may be the mast cell that releases agents that recruit leukocytes to the
      appropriate site at risk. The objective of this study was to evaluate the early
      mechanisms involved in mast cell-induced leukocyte recruitment. We used
      intravital microscopy to visualize leukocyte-rolling flux and adhesion in single
      25 to 40 microns venules in mesenteric preparations that were treated with the
      mast cell-degranulating agent, compound 48/80 (CMP 48/80). Superfusion of the rat
      mesentery with CMP 48/80 caused a dose-dependent rise in the number of rolling
      and adherent cells, events significantly reduced by: 1) mast cell stabilizers,
      ketotifen, or cromolyn, and 2) chronic treatment with CMP 48/80 to deplete mast
      cell constituents. The increase in leukocyte flux associated with CMP 48/80 was
      blocked by diphenhydramine (H1-receptor antagonist) and an anti-P-selectin Ab
      (PB1.3), but not by the 5-lipoxygenase inhibitor, MK 886. The reduction in the
      flux of rolling leukocytes translated into fewer adherent leukocytes with
      diphenhydramine or PB1.3. The CMP 48/80-induced rise in leukocyte adhesion, but
      not leukocyte flux, was reduced by the platelet-activating factor (PAF)-receptor
      antagonist (WEB 2086) and an anti-CD18 Ab (CL26). MK 886 did not prevent the
      increased leukocyte adhesion. In vitro data revealed that mast cell-derived PAF
      induced essentially all of the leukocyte adhesion to endothelium or protein
      coated plastic. These data suggest that mast cell degranulation induces P
      selectin-dependent leukocyte rolling and CD18-dependent leukocyte adhesion via
      histamine and PAF, respectively.

PMID- 7814886
TI  - Induction of human serum amyloid A in Hep 3B cells by IL-6 and IL-1 beta involves
      both transcriptional and post-transcriptional mechanisms.
AB  - Previous studies of murine serum amyloid A (SAA) regulation during inflammatory
      states or following exposure to macrophage-conditioned medium have raised the
      possibility that both post-transcriptional and transcriptional mechanisms
      participate in induction of this family of proteins. Since IL-6 and IL-1 have
      been shown to induce SAA in human hepatoma cell lines, we explored the
      possibility that these cytokines might induce human SAA through post
      transcriptional as well as transcriptional mechanisms. In kinetic studies, we
      found that continuous exposure of Hep 3B cells to either IL-6 or IL-1 beta alone
      caused only minimal increases in SAA mRNA and marginal increases in transcription
      (as measured by nuclear runon). In contrast, the combination of these cytokines
      led to a 23-fold increase in transcription, maximal at 12 h, with continuing
      increase in mRNA, achieving levels more than 1,000-fold greater than baseline by
      72 h. This massive disparity between increases in mRNA and in transcription rate
      strongly supports the participation of post-transcriptional mechanisms in SAA
      induction by (IL-6 + IL-1 beta), whereas the lag between peaks of transcription
      and mRNA abundance reflects a relatively slow degradation rate of SAA mRNA. As
      observed by other workers, mean size of SAA mRNA decreased progressively over the
      course of incubation. Simultaneous kinetic studies of complement factors B and
      C3, haptoglobin, and alpha-1 protease inhibitor revealed several different
      patterns of response to IL-6 and IL-1 beta.

PMID- 7814887
TI  - Antitumoral properties of aged human monocytes.
AB  - It is known that older people are more sensitive to cancer and infectious agents
      and need more time to recover from such disorders. Can this difference in
      sensitivity to cancer and infections between elderly and younger people be a
      result of a difference in their immune systems and, more specifically, in the way
      monocytes react to infectious agents and cancer cells? To determine what happens
      after cells have aged, human monocytes were purified from young donors
      (approximately 25 years of age) and from older donors (65 years of age or older)
      and tested for their ability to respond to the polyclonal activator LPS. Our
      results showed that monocytes from aged donors (aged monocytes), when compared
      with monocytes from younger donors (young monocytes) did lose part of their
      cytotoxicity against tumor cells (A375 human melanoma cells and L929 murine
      fibroblast cells). In addition, aged monocytes displayed a sharp decrease in IL-1
      secretion, but did display the intracellular 31 kDa IL-1 precursor. Moreover,
      aged monocytes displayed a decrease in the production of reactive oxygen
      intermediates such as NO2 and H2O2. Finally, aged monocytes stimulated by LPS
      displayed an increase in intracellular cyclic AMP and have lost their protein
      kinase C translocation from the cytosol to the plasma membranes. These results
      suggest that age affects the immunologic and antitumoral properties of human
      monocytes.

PMID- 7814888
TI  - Complement component C7 is a plasminogen-binding protein.
AB  - Ab deposition, whether by reaction with the specific Ag or by preformed immune
      complexes, is followed by activation and deposition of complement components.
      Tissue destruction is observed in the Ab- and complement-induced lesions. The
      proteolytic enzyme plasmin is thought to participate in the Ab- and complement
      mediated organ pathology. Plasmin is generated from plasma-derived plasminogen by
      cell-derived plasminogen activators (PAs). Two types of PAs are known, urokinase
      type PA (uPA) and tissue-type PA (tPA). We investigated whether the PA system and
      the complement system can interact to promote local plasmin generation. Among the
      terminal complement components C5b6, C7, C8, and C9, the nonenzymatic component
      C7 is a plasminogen-binding protein. Radioligand binding studies revealed that
      the isolated component, as well as C7 after its incorporation into the terminal
      complement complex C5b-9, can bind plasminogen. Binding was inhibited by the
      lysine analogues 6-aminohexanoic acid and tranexamic acid, implicating the lysine
      binding sites of plasminogen into the binding interaction. tPA-mediated
      plasminogen activation was enhanced in the presence of C7. Based on these
      findings, an interaction is proposed between the complement system and the
      plasminogen activator system; a mechanism that may focus plasmin activity to
      structures that have been tagged by Ab and complement deposition.

PMID- 7814889
TI  - Chlorpromazine amplifies macrophage-dependent IL-10 production in vivo.
AB  - Chlorpromazine (CPZ) has potent immunomodulatory effects in vivo; it induces
      humoral autoimmunity in up to 50% of patients, inhibits delayed-type
      hypersensitivity reactions, and suppresses lethal immune hyperactivation in
      animal models of septic shock. Here, we show that in an in vivo model of acute
      superantigen-driven immune activation, CPZ independently down-regulates the
      production of various T cell-derived lymphokines (IL-2, IFN-gamma, IL-4, TNF, and
      GM-CSF) and up-regulates the secretion of IL-10. Whereas only low, if any, serum
      IL-10 levels are detectable by ELISA after injection of CPZ, bacterial LPS, or
      staphylococcal enterotoxin B (SEB) alone, simultaneous administration of CPZ +
      LPS or CPZ + SEB causes a significant increase in IL-10 production in vivo. CPZ
      mediated amplification of the SEB-driven CPZ secretion is accompanied by an
      enhanced IL-10 mRNA accumulation, as shown by PCR analysis and in situ
      hybridization. Determination of IL-10 production in mice lacking T cells, B
      cells, or phagocytes revealed that SEB + CPZ-induced IL-10 was produced by
      phagocytic cells, but not by lymphocytes, a finding that is in accord with the
      distribution of splenic cells transcribing the IL-10 gene in response to SEB +
      CPZ. Moreover, these data indicate that bacterial superantigen can directly
      stimulate tissue phagocytes, even in the virtual absence of T lymphocytes. The
      blockade of dopamine type 1 (D1) but not type 2 (D2) receptors abolishes the CPZ
      effect on IL-10 production. Inhibition of Th1 and Th2 lymphokine production by
      CPZ is not mediated by dopamine receptors and is independent of IL-10 up
      regulation. These findings may explain the mechanism by which CPZ and related
      drugs enhance humoral autoimmune reactions, block cellular immune responses, and
      prevent lethal septic shock in vivo.

PMID- 7814890
TI  - Heparan sulfate initiates signals in murine macrophages leading to divergent
      biologic outcomes.
AB  - We have previously shown that the interaction of heparan sulfate (HS), a
      constituent of cell surfaces and extracellular matrices, with murine macrophages
      causes activation of the macrophages leading to the production of cytokines and
      PGE2 and profound changes in the cellular immune responses triggered by the
      macrophages. Here we describe the molecular mechanisms that underlie these
      immunoregulatory changes. We demonstrate that HS delivers signals to macrophages
      through at least two pathways, one involving the activation of a tyrosine kinase
      and of nuclear factor-KB, and the other involving the activation of protein
      kinase C and the elevation of intracellular calcium. The former pathway is
      associated with the production of IL-6, and the latter pathway is associated with
      the production of PGE2. Our findings suggest a model in which components of the
      microenvironment, such as HS, may determine the functional state of an APC,
      thereby modifying immune responses.

PMID- 7814892
TI  - Divergent effects of chronic HIV-1 infection on human thymocyte maturation in
      SCID-hu mice.
AB  - We have recently developed a modified SCID-hu mouse model in which the implanted
      human thymus and liver (hu-thy/liv) and human peripheral T cells become infected
      with HIV-1 after i.p. inoculation. By using this model, we evaluated the effect
      of HIV-1 infection on thymic maturation and observed that different HIV-1 strains
      had divergent effects of thymic maturation. Although minimal effects on continued
      thymopoiesis in the hu-thy/liv implant were observed after chronic infection with
      two primary patient isolates, HIV-1(28) and HIV-1(59), and with HIV-1ADA, HIV-1Ba
      L, HIV-1JR-CSF, HIV-1JR-FL, and HIV-1SF162, significant thymocyte depletion was
      detected after infection with HIV-1IIIB and HIV-1RF. Thus, the effect of HIV-1
      infection on thymocyte maturation may depend upon the strain of HIV-1 infecting
      the thymus. Despite the minimal effects on thymopoiesis observed in the hu
      thy/liv implanted in SCID-hu mice 6 mo after infection with HIV-1(28),
      significant changes were seen in the human T cell population circulating in the
      peripheral blood of these mice. These changes ranged from an inversion of the
      CD4/CD8 ratio of peripheral human T cells in some SCID-hu mice to the almost
      complete depletion of peripheral human T cells observed in other SCID-hu mice.
      Because these effects were associated with the detection of HIV-1 infection of
      the peripheral human T cells, these modified SCID-hu mice should prove to be a
      valuable model for investigating the effects of chronic HIV-1 infection on the
      peripheral human T cell population.

PMID- 7814891
TI  - Balance between IL-1 beta, TNF-alpha, and their specific inhibitors in chronic
      renal failure and maintenance dialysis. Relationships with activation markers of
      T cells, B cells, and monocytes.
AB  - Patients with end-stage renal disease present an immunodeficiency that
      paradoxically coexists with activation of most immunocompetent cells, and the
      roles of chronic uremia and maintenance dialysis are poorly understood. We
      determined circulating levels of IL-1 beta and IL-1Ra, TNF-alpha and its soluble
      receptors (TNF-sR55 and TNF-sR75), and activation markers of T cells (soluble
      CD25), B cells (soluble CD23), and monocytes (neopterin) in a large cohort of
      undialyzed patients at various stages of chronic renal failure and in dialyzed
      patients on maintenance hemodialysis or chronic peritoneal dialysis. The
      progression of uremia was associated with a gradual increase in soluble CD25,
      CD23, and especially neopterin levels. Although IL-1 beta could not be detected,
      IL-1Ra levels were significantly increased from the earliest stage of renal
      failure. Plasma levels of TNF-alpha, TNF-sR55, and TNF-sR75 progressed with the
      severity of renal failure and correlated with soluble CD25, CD23, and neopterin
      levels, whereas IL-1Ra levels correlated exclusively with TNF-sR55 levels.
      Compared with undialyzed patients, levels of IL-1 beta were higher in patients on
      maintenance hemodialysis, whereas those of IL-1Ra were lower and decreased
      further at the end of dialysis sessions. In contrast, both TNF-sR55 and TNF-sR75
      levels were significantly higher than in undialyzed patients and increased
      further at the end of dialysis sessions in the absence of an increase of TNF
      alpha. Such an imbalance between cytokines and their inhibitors may play a
      pivotal role in the multifaceted process of immune dysfunction.

PMID- 7814893
TI  - Synergistic effect of rapamycin and cyclosporin A in the treatment of
      experimental autoimmune uveoretinitis.
AB  - Immunosuppressive drugs currently available for the treatment of autoimmune
      diseases display a narrow therapeutic window between efficacy and toxic side
      effects. The use of combinations of drugs that have a synergistic effect may
      expand this window and reduce the risk of toxicity. We evaluated the combination
      effect of rapamycin (Rapa) and cyclosporin A (CsA) in an autoimmune disease model
      of the eye. The dose-effect relationship of Rapa with CsA was measured in vitro
      on the inhibition of proliferation of retinal S-Ag-primed lymphocytes. A median
      effect analysis was performed and a combination index (CI) calculated for 50%
      inhibition of proliferation. Rapa and CsA were markedly synergistic over a wide
      dose range (lowest CI = 0.31). Calculated dose reduction factors indicated that
      Rapa could be reduced nine-fold and CsA reduced five-fold when these drugs were
      used in combination. These reduced doses were tested in vivo for the treatment of
      experimental autoimmune uveoretinitis (EAU). Twelve of 15 rats treated with CsA,
      2 mg/kg/day, developed EAU with a median severity of 2.5. Fourteen of 15 rats
      treated with Rapa, 0.01 mg/kg/day, developed EAU with a median severity of 3.25.
      Complete inhibition of EAU was achieved in all 15 animals treated with the
      combination of Rapa and CsA (combined vs CsA alone, p < 0.0002; combined vs Rapa
      alone, p < 0.00001). The demonstrated synergistic relationship between Rapa and
      CsA will allow the use of reduced doses of each drug to achieve a therapeutic
      effect. The use of lower doses may reduce the toxicity of these drugs for the
      treatment of autoimmune uveitis.

PMID- 7814894
TI  - TNF-alpha expression by resident microglia and infiltrating leukocytes in the
      central nervous system of mice with experimental allergic encephalomyelitis.
      Regulation by Th1 cytokines.
AB  - The inflammatory cytokines IFN-gamma and TNF-alpha have been demonstrated in
      various autoimmune diseases, and are thought to participate in the induction and
      pathogenesis of disease. TFN-alpha is a cytopathic cytokine that is cytotoxic for
      oligodendrocytes in vitro and has been implicated in the pathology of multiple
      sclerosis and its animal model experimental allergic encephalomyelitis (EAE). We
      used reverse transcriptase (RT)-PCR to study the kinetics, cellular source, and
      regulation of cytokine gene expression in the central nervous system (CNS) of
      SJL/J mice with myelin basic protein-induced EAE at different stages of the
      disease. The expression of CD3, IL-2, IFN-gamma, and TNF-alpha mRNA was barely
      detectable in the CNS of unmanipulated mice or mice that were immunized with
      adjuvant but showed no symptoms. These mRNAs were readily detectable in the CNS
      of mice during peak disease, then coordinately dropped to background levels
      during remission. Analysis of cells isolated from the CNS of mice with acute EAE
      showed that the Th1 cytokines, IL-2 and IFN-gamma, were produced by infiltrating
      CD4+ T cells. In contrast, TNF-alpha was predominantly transcribed by non-T
      mononuclear CNS cells, the majority of which were identified as microglia and
      macrophages by their Mac-1 phenotype. Microglia could be discriminated by their
      low expression of CD45. Incubation of freshly derived, adult microglia from
      normal, uninfiltrated, CNS with activated Th1 supernatant induced the production
      of TNF-alpha mRNA. Therefore, TNF-alpha is made by both CNS-resident microglia
      and infiltrating macrophages during EAE, and this production is tightly
      controlled by cytokines secreted by infiltrating CD4+ T cells.

PMID- 7814895
TI  - "Anticardiolipin" autoantibodies recognize beta 2-glycoprotein I in the absence
      of phospholipid. Importance of Ag density and bivalent binding.
AB  - "Anticardiolipin" autoantibodies (aCL) bind to anionic phospholipids only in the
      presence of beta 2-glycoprotein I (beta 2GPI), a phospholipid-binding plasma
      protein. The exact role of beta 2GPI in the antigenic specificity of these
      autoantibodies is unclear, however. Experiments were performed to determine
      whether aCL recognize beta 2GPI in the absence of phospholipid or neo-Ags formed
      as a consequence of the beta 2GPI-phospholipid interaction. Although aCL+ IgG
      fractions did not bind to beta 2GPI alone in ELISAs that used standard
      polystyrene immunoassay plates, significant specific binding was detected when
      beta 2GPI was coated on gamma-irradiated ("high binding") polystyrene plates.
      This difference was associated with the greater density of beta 2GPI immobilized
      on the gamma-irradiated plates. Fab' fragments of patient IgG demonstrated little
      or no binding to immobilized beta 2GPI in ELISA, indicating a critical role for
      Ab bivalency. Inhibition studies of three aCL+ IgG fractions confirmed their
      specificity for beta 2GPI and demonstrated low affinity binding to fluid-phase
      beta 2GPI (Kd values of approximately 10(-5) M). aCL binding to beta 2GPI was not
      a result of phospholipid contamination of the assays, as determined by
      microphosphate assay and by lipid extraction of IgG and beta 2GPI preparations.
      In summary, these experiments indicate that IgG aCL are intrinsically low
      affinity Abs to beta 2GPI. Ab binding to beta 2GPI on a microtiter plate or
      anionic phospholipid membrane is dependent upon the marked increase in avidity
      provided by engagement of both Ag binding sites of a given IgG molecule. The data
      support the hypothesis that phospholipid-bound beta 2GPI is the physiologic
      target of aCL.

PMID- 7814896
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 biological effects.

PMID- 7814897
TI  - New approaches in the serodiagnosis of hydatid disease.

PMID- 7814898
TI  - Clinical profile of acute myocardial infarction in women.
AB  - Three hundred fifty women with acute myocardial infarction who formed 17% of
      total myocardial infarction cases admitted were studied. Only 7.7% were below 40
      years. Infarction occurred mostly (80%) in postmenopausal period. History of
      previous illness was present in 73% cases. Risk factors were present in majority
      (75%) of the cases. Common risk factors in Indian women were hypertension in 49%
      cases and diabetes mellitus in 34% cases. None were using oral contraceptives and
      it occurred mostly (77%) in multiparous women. Majority (94%) presented with
      typical chest pain. Premonitory symptoms occurred in only a few patients (14%).
      Complications occurred more frequently in 40% cases. Mortality rate appears to be
      high (18%); the commonest cause being cardiogenic shock.

PMID- 7814899
TI  - Fallacies of the fine needle aspiration cytology of surgical lesions of liver.
AB  - Seventy-six cases of surgical hepatomegaly were subjected to fine needle
      aspiration cytology (FNAC) for initial diagnosis. Primary malignancies, as
      suspected clinically with adjunction of other investigative procedures, were 29
      cases of whom 25 were confirmed by biopsy or therapy. Secondary deposits in liver
      were 27 of whom 15 were confirmed by therapy. Inflammatory lesions were 9 of whom
      6 were confirmed by therapeutic response with specific therapy. Benign lesions
      were 10 of whom 5 were confirmed by surgery. Diagnosis of malignancies of liver
      is rather easier than that of benign lesions like hydatid cysts of liver which
      were Casoni's test negative; and hepatocellular adenoma, as the aspirate in the
      former is clear fluid and that of the latter is only normal looking liver cells.
      Thus, in respect of benign lesions of liver, FNAC diagnosis may be clinched after
      due consideration to the clinical findings, radiological and ultrasonographic
      findings and ultimately confirmed by exploration. Thus the fallacy lies in
      aspiration of normal looking liver cells whereby the histology may prove it to be
      hepatocellular adenoma, well differentiated hepatocellular carcinoma and
      secondary deposits where the exact site has not been hit. Ultrasonogram (USG)
      guidance helps in these cases where the same facility is available. This fallacy
      can again be avoided, where USG guidance is not available, by imparting due
      importance to clinical findings, USG findings and also by repeat smear.

PMID- 7814900
TI  - Diagnostic and prognostic significance of lactate dehydrogenase in cerebrospinal
      fluid in patients of meningitis.
AB  - Activity of lactate dehydrogenase was measured in cerebrospinal fluid in 60 cases
      of meningitis (35 pyogenic, 18 tuberculous and 7 viral). Thirty age and sex
      matched healthy controls were taken to find out its diagnostic and prognostic
      significance in meningitis. The cerebrospinal fluid lactate dehydrogenase
      activity was significantly higher (p < 0.001) in cases of pyogenic meningitis and
      tuberculous meningitis as compared to the control group. The maximum elevation
      was seen on the 1st day in all types of meningitis but the activity declined
      significantly thereafter in patients of pyogenic meningitis who recovered without
      complications. However, in 2 cases of pyogenic meningitis and 5 cases of
      tuberculous meningitis who survived with complications, the lactate dehydrogenase
      activity on subsequent estimations increased serially. Further, the basal lactate
      dehydrogenase activity in 9 cases of pyogenic meningitis (who expired) was higher
      than those who survived without complications. The basal lactate dehydrogenase
      activity in pyogenic meningitis was significantly higher (p < 0.05) as compared
      to tuberculous meningitis and viral meningitis patients (p < 0.02) in this study.

PMID- 7814901
TI  - Epidemiological studies of blood groups in the district of Bankura with special
      reference to tribals.
AB  - Distribution of ABO blood groups was studied in 4301 subjects, both tribals and
      non-tribals of the district of Bankura in West Bengal. It was observed that group
      'O' blood was found in most cases and group 'AB' was seen in least number of
      cases. It was also found that there was no significant difference in distribution
      of blood groups between the tribals and non-tribals.

PMID- 7814902
TI  - A preliminary study of glycosylation of hair in diabetes mellitus.
AB  - Glycosylation of hair was studied in 30 diabetic (15 IDDM and 15 NIDDM) patients
      and in 30 age and sex matched healthy non-diabetic subjects. A positive
      correlation occurs between glycosylation of proximal portion of hair and the
      simultaneously measured glycosylated haemoglobin. The hair glycosylation remains
      stable along the length of hair from scalp to tip in normal subjects and suggests
      that a sufficiently long hair sample may offer a long term record of degree of
      hyperglycaemia. This may be useful in the investigation of hyperglycaemia and
      microvascular complications of diabetes mellitus. The level of glycosylation of
      hair is independent of duration of the disease, age, sex and race of the patient
      and colour of the hair, thus providing a universal index of hyperglycaemia in the
      control of diabetic state. Glycosylation of hair is perhaps the most non-invasive
      technique readily acceptable to the patients and yet provides a fairly accurate
      and reliable information regarding hyperglycaemia in the preceding duration in
      which the hair has been grown.

PMID- 7814903
TI  - Incidence of cancer breast at Aligarh.
AB  - Breast cancer is a worldwide problem but its frequency varied from place to
      place. One hundred twenty-four breast cancer cases were reported during the ten
      years of survey at Aligarh constituting 12.4% of all malignant lesions. Peak
      incidence was found between the age of 41 and 50 years. More patients were from
      lower socio-economic group belonging to both Hindu as well as Muslim communities.
      Nearly 90% of cases had their menarche by the age of 14 years. Male breast cancer
      was 4%. Right breast was more commonly affected than that of the left. The upper
      and outer quadrant was involved in more than one-third cases and more than half
      the lesions occurred in upper half. There were 97.6% of epithelial and 2.4% of
      stromal tumours. Among epithelial tumours, highest incidence (72.38%) was that of
      invasive duct carcinoma followed by medullary, colloid and Paget's disease.

PMID- 7814904
TI  - Current trends in blood banking.

PMID- 7814905
TI  - Floating intraperitoneal hydatidosis.

PMID- 7814906
TI  - Commercialisation of medical education--a review of capitation fee colleges.

PMID- 7814907
TI  - Kinesiophysiological consideration in improving sports performance and in
      rehabilitative measures.

PMID- 7814908
TI  - Visceral leishmaniasis treated with rifampicin and co-trimoxazole.

PMID- 7814909
TI  - Professional stress in paediatric practice.

PMID- 7814910
TI  - Effective coping with stroke disability in a community setting: the development
      of a causal model.
AB  - A proposed causal model based upon Lazarus' theory of psychological stress and
      coping was tested in a sample of 75 persons disabled by stroke. Coping
      constraints such as demographic and stroke factors were hypothesized to affect
      resources (perceived availability of social support, perceived effectiveness of
      social support, social contact), stress appraisal, coping behavior and coping
      effectiveness. Although the model did not fit the data, several path coefficients
      within the model were statistically significant. Functional status was positively
      related to resources and negatively related to the stressor. Resources were
      negatively related to the stressor and positively related to coping
      effectiveness. It was noted that the buffering effect of social support was
      related to the level of disability of the stroke person. Persons with functional
      disability following stroke also had decreased social contact, perceived less
      availability of social resources and increased threat to physical well-being, and
      had reduced coping effectiveness.

PMID- 7814911
TI  - Venous stroke in the pregnant and postpartum patient.
AB  - Cerebral infarction is often considered a disease of middle-aged or elderly
      patients; it is uncommon in young adults. Venous stroke, however, has been
      recognized for many years as a hazard in young females during pregnancy and the
      postpartum period. Occlusion by thrombus is the most common abnormality and can
      be caused by alteration in blood viscosity, changes in blood volume and a
      hypercoagulable state. Because the neuroscience nurse may be faced with the
      challenge of caring for this different type of patient, an understanding of
      venous stroke, its manifestations and treatment is necessary in order to
      establish a plan of care.

PMID- 7814912
TI  - When the nurse says "he's just not right": patient cues used by expert nurses to
      identify mild head injury.
AB  - Many patients with mild head injury are discharged from the hospital without
      recognition of their true rehabilitative needs. This qualitative study was
      designed to describe what patient cues the expert nurse uses when making an
      assessment of mild head injury. Although the majority of cues the participants
      identified are supported in the head injury literature, several other cues, not
      previously linked with the assessment of mild head injury, were found. The
      identification of these aspects of the nursing assessment provides new insight
      into the art of neuroscience nursing.

PMID- 7814913
TI  - Creutzfeldt-Jakob disease: a review.
AB  - Creutzfeldt-Jakob disease (CJD) is a rapidly progressive and ultimately fatal
      disorder of the central nervous system. CJD occurs worldwide with an incidence of
      approximately .5-1 new cases per million population per year. Despite numerous
      epidemiological and laboratory studies, the etiologic agent and mode of
      transmission remain unclear. Clinical diagnosis is challenging and is based on
      clinical symptoms. No specific treatment is available and medical management
      remains limited to supportive care. Health care workers must be well informed
      about necessary precautions and decontamination procedures. Nurses play a major
      role in providing supportive care, educating community organizations and agencies
      about CJD and assisting the family through the grieving process.

PMID- 7814915
TI  - Understanding chronic pain after spinal cord injury.
AB  - Survivors of spinal cord injury (SCI) have a range of sensory experiences
      following the trauma. Acute pain commonly accompanies the injury and recedes as
      healing occurs. Following the initial event, most spinal cord-injured individuals
      experience phantom sensations and many suffer chronic pain. In extreme cases,
      chronic pain can become the most disabling sequela, leading to chemical
      dependency, severe depression and even suicide. Pain arising from injury to
      peripheral and central neural structures possesses unique characteristics that
      distinguish it from persisting acute pain and phantom sensations. Ironically, it
      is experienced in regions of the body that are anesthetic or possess diminished
      or altered sensation as a consequence of the injury. The qualitative features of
      the pain have been linked to structural and functional alterations that have been
      documented in peripheral and central neural structures following SCI. An
      understanding of these unique relationships provides direction for future
      research.

PMID- 7814914
TI  - Interruption of enteral feedings in head injured patients.
AB  - This study was undertaken to determine differences between caloric intake and
      requirements of critically ill, enterally fed, neurosurgical and neurotrauma
      patients and to determine the nature and frequency of interruptions in enteral
      feedings in this same population. This descriptive, prospective study was
      conducted in a surgical intensive care unit (ICU) in a university teaching
      hospital. The sample consisted of 52 mechanically ventilated, critically ill
      patients with a mean age of 48.96 years who were receiving enteral nutrition for
      at least two days. Basal energy requirements, daily nutritional intake and
      enteral feeding interruption characteristics were recorded for a total of 586
      study days. Underfeeding due to interruptions occurred in the majority of
      patients for the first eight days following initiation of enteral feeding.
      Reasons for underfeeding were interruptions of continuous tube feedings due to
      medication administration via the feeding tube (31%), feeding tube displacement
      (27%), surgery (12%), ileus (9%), radiologic studies (9%), airway management
      (8%), bedside procedures (3%) and agitation (1%). The frequency of these enteral
      feeding interruptions may indicate inadequate nutritional support, highlighting
      the importance of performing daily nutritional monitoring to prevent
      malnutrition.

PMID- 7814916
TI  - Living with multiple sclerosis: the experience of chronic sorrow.
AB  - This qualitative nursing research study investigated the occurrence of chronic
      sorrow in individuals with multiple sclerosis. Using the Burke/NCRCS Chronic
      Sorrow Questionnaire (Individual Version), 10 participants were interviewed. Data
      were analyzed in collaboration with one other researcher. Of the participants,
      80% evidenced the presence of chronic sorrow in their lives. Data clearly
      indicated that feelings of chronic sorrow occurred periodically over a protracted
      span of time when some event reminded participants of their chronic situation.
      The nursing roles of empathetic presence and caring professional helped
      participants the most in dealing with their feelings of chronic sorrow.

PMID- 7814917
TI  - Memory aging research and memory support in the elderly.
AB  - In research on cognitive processes, two important areas are emerging: the
      individual's awareness of his or her own ability to remember and the ways in
      which individuals monitor their memory performance. While forgetfulness and
      memory complaints in those with advancing age may indicate cognitive decline, it
      need not always be a deficit. Practice in a supportive environment can facilitate
      memory of the older person. Teaching family members about the effective
      techniques of cued recall and practice are beneficial and important to include in
      nursing care.

PMID- 7814918
TI  - Coordinated care for the neuroscience patient: future directions.
AB  - A coordinated care model was developed on a neuroscience unit to achieve positive
      outcomes in a cost-effective environment. This included the development of a
      patient care coordinator (PCC) role, critical paths and a system for variance
      tracking. The PCC was responsible for coordinating care of patients and ensuring
      that patients progressed toward expected outcomes. Multidisciplinary critical
      paths were developed for four medical diagnoses. To evaluate the effectiveness of
      the program, an analysis of length of stay data, cost comparison, patient and
      staff satisfaction, and variance reports of one critical path, the microvascular
      decompression for trigeminal neuralgia were completed. Results from the pilot
      project were positive and provided valuable information for the use of
      coordinated care as a hospital-wide patient care delivery model.

PMID- 7814919
TI  - Secondary brain injury and the role of neuroprotective agents.
AB  - Secondary brain injury is associated with high mortality and morbidity rates.
      Reversible causes of secondary injury, including hypoxemia, hypotension and
      increased intracranial pressure need to be anticipated and prevented, when at all
      possible. In addition, further understanding of the cellular and metabolic
      alterations associated with delayed brain injury and the role of neuroprotective
      agents in the prevention of said injury will hopefully result in improved
      neurologic care. One challenge for health care providers in the years ahead will
      be to limit the extent of injury after the initial event, thereby improving
      outcomes.

PMID- 7814920
TI  - Three-dimensional analysis for skeletal problems.

PMID- 7814922
TI  - Stability and effect on the soft tissue profile of mandibular advancement with
      sagittal split osteotomy and rigid internal fixation.
AB  - The stability and the effect on the soft tissue profile of mandibular advancement
      with sagittal split osteotomy and rigid internal fixation was studied
      prospectively in 30 consecutive patients, 17 to 32 years old, who had a distal
      occlusion. Profile roentgen cephalometric recordings were made immediately before
      and shortly after surgery as well as 13 months postsurgically. The mean
      advancement of the mandible 3 to 8 days after surgery was 5 mm. On average, there
      was only a small increase in the anterior facial height. At the follow-up after
      13 months, the advancement of the mandible had, in most cases, partially relapsed
      so that the median net effect was 70%. In six subjects, however, the mandible had
      advanced slightly further. The skeletal relapse was partially masked by
      compensatory movements of the maxillary incisors so that the mean net effect on
      the overjet was 83%. The amount of relapse was positively correlated to the
      magnitude of advancement during surgery. Likewise, a postsurgical relapse of the
      anterior facial height was positively correlated to the magnitude of advancement
      during surgery. Likewise, a postsurgical relapse of the anterior facial height
      was positively correlated to the magnitude of the vertical surgical displacement
      anteriorly and posteriorly. The soft tissue chin closely followed the underlying
      hard tissue. The mean net effect on the labial fold, however, was smaller, 88% of
      the mandibular advancement. The net effect on the lower lip was 66% of the
      advancement of the mandibular incisor.

PMID- 7814921
TI  - Stability following superior repositioning of the maxilla by Le Fort I osteotomy:
      five-year follow-up.
AB  - Changes in dental and skeletal relationships were evaluated 5 years
      postsurgically in 49 patients whose maxilla had been superiorly repositioned by a
      Le Fort I osteotomy. All of the patients had at least 2 mm of intrusion at the
      maxillary incisor and molar; none had a mandibular ramus osteotomy or other
      osteotomy except genioplasty. Only 6.5% had 2 mm or greater of net vertical
      change in skeletal or dental landmarks at 1 year postsurgery. From 1 to 5 years
      postsurgery, minimal changes in skeletal and dental landmarks occurred in the
      majority of the patients, but approximately 25% of the patients showed 2 mm or
      more of downward movement of the maxilla and/or eruption of maxillary teeth,
      leading to downward-backward rotation of the mandible. Only one patient had more
      than 1 mm of open bite on long-term follow-up. An increase in overbite, resulting
      from incisor eruption, was noted in 14%, and an increase in overjet occurred in
      12% as the mandible rotated. It appears that modest long-term skeletal and dental
      changes occur in some surgically treated long-face patients. The likelihood of
      long-term change was not related to the age of the patient, stability during the
      first postsurgical year, or segmentation of the maxilla at surgery.

PMID- 7814924
TI  - Coordination of the orthosurgical treatment program.
AB  - Health care reform, current changes in the third-party payer system, and the
      evolution of orthognathic surgery mandate superior communication between the oral
      and maxillofacial surgeon and orthodontist. This article describes a successful
      approach to coordinating the entire orthosurgical treatment program to improve
      treatment outcome and patient satisfaction.

PMID- 7814925
TI  - Correction of mandibular dentoalveolar retrusion by segmental mandibular surgery.
AB  - Mandibular dentoalveolar retrusion is a common problem that often can be related
      to missing or extracted teeth in the mandibular arch. The correction of this type
      of malformation through surgical mandibular advancement to eliminate the large
      overjet significantly increases the chin prominence, resulting in a poor facial
      appearance. With the use of a combined orthodontic and surgical treatment that
      includes segmental osteotomies of the anterior part of the mandible, this
      negative effect can be avoided and arch length can be restored. This procedure
      was carried out in three patients aged 26 to 33 years. The bony spaces created
      distal to the anterior segment were filled with iliac bone grafts. At the end of
      the orthodontic treatment, the missing premolars were replaced with conventional
      fixed dentures, bonded prostheses, or implants.

PMID- 7814923
TI  - Comparison of soft tissue facial morphometry in children with Class I and Class
      II occlusions.
AB  - Three-dimensional soft tissue facial morphometry was investigated in a sample of
      167 children aged 6 to 9 years by using a new noninvasive computerized method.
      For each child, 16 cutaneous facial landmarks were automatically collected by a
      system consisting of two infrared CCD cameras, real-time hardware for the
      recognition of markers, and software for the three-dimensional reconstruction of
      the x, y, and z coordinates of landmarks. From these landmarks, 15 linear and 10
      angular measurements and five linear distance ratios were computed. For each age
      class, mean values were computed for all children with a bilateral Angle Class I
      occlusion (modified according to Katz) and compared with values obtained in
      children with a bilateral Class II occlusion. Most of the differences involved
      three-dimensional angular measurements: Class II children had more convex faces
      in the sagittal plane and a less prominent mandible than did Class I children. No
      differences were found in the linear measurements. Only the lower facial height
      ratio was different between the two occlusion groups, but the difference was not
      consistent among all the age groups.

PMID- 7814926
TI  - Treatment of Class II division 2 malocclusion with combined bilateral sagittal
      split osteotomy and total subapical osteotomy.
AB  - This paper describes a modification of the combined bilateral sagittal split
      osteotomy and total subapical osteotomy procedure; a representative case treated
      with this approach is presented. In addition, diagnostic and treatment planning
      considerations for the comprehensive surgical-orthodontic therapy of individuals
      presenting with differential sagittal discrepancy between the mandibular corpus
      and symphysis are discussed, along with limitations of diagnostic criteria
      commonly used in cephalometric appraisal of the facial soft tissue outline.

PMID- 7814927
TI  - Cephalometric characteristics of open bite in adults: a three-dimensional
      cephalometric evaluation.
AB  - The purpose of this study was to evaluate the morphogenetic characteristics that
      contribute to the development of open bite in adults. The linear dimensions of
      various maxillofacial structures of adults with anterior open bite were compared
      to those of a normal adult population. Lateral and posteroanterior cephalometric
      radiographs were taken of 22 men and 34 women who exhibited an anterior open bite
      of at least 2 mm. A control group consisted of 27 men and 33 women who had an
      orthognathic profile, a normal skeletal pattern, and a Class I occlusion. In both
      men and women with open bite, total facial height (nasio menton) and three
      dentoalveolar heights--anterior maxillary (maxillary central incisor-palatal
      plane), posterior maxillary (maxillary first molar-palatal plane), and anterior
      mandibular (mandibular central incisor-mandibular plane)--were significantly
      greater than the same dimensions in the control groups. Ramus height (condylion
      gonion) and depth, gonial depth, maxillary length (anterior nasal spine-posterior
      nasal spine), and facial length (basion-point A) were significantly smaller in
      those with open bite. Mandibular length (gonion-pogion) and facial width were
      significantly smaller only in the female open bite group. Both male groups had
      significantly larger measurements than did the female groups. The only exceptions
      were the nasal width in the control groups and the ramus depth in the open bite
      groups, for which there were no statistically significant differences between men
      and women.

PMID- 7814928
TI  - Condylar resorption in orthognathic surgery: a retrospective study.
AB  - A retrospective study was performed to examine the occurrence of condylar atrophy
      in connection with orthognathic surgery. Patients with high-angle mandibular
      deficiency (n = 29) were selected from among those who underwent bimaxillary
      osteotomy (n = 93) during the period from January 1987 through December 1990.
      This group of 29 was examined for shortening of the ascending ramus of the
      mandible because of condylar resorption. In 9 of these 29 (31%), the ramus had
      resorbed more than 2 mm, or more than 6% of the total length of the ramus. All 9
      of these patients were female. There was no correlation between resorption and
      age, the amount of retrognathism, or the presence of preoperative
      temporomandibular joint dysfunction. Female patients with high-angle
      retrognathism should be informed of the possibility of postoperative condylar
      resorption and should be followed with radiographic controls for at least 2 years
      after surgery.

PMID- 7814929
TI  - [The effect of assisted hatching on patients repeatedly failed to conceive by in
      vitro fertilization].
AB  - Assisted hatching (AHA) techniques were used in 67 patients who had repeatedly
      failed to achieve conception by conventional IVF-ET in spite of replacement by
      good quality embryos. The age of the female patients ranged from 28 to 44 years
      and the causes of their infertility included tubal factors (n = 33), male
      infertility (16), endometriosis (8) and unexplained causes (21). Zona drilling
      with acid Tyrode's solution was performed on 248 embryos in 88 cycles
      approximately 72 hours after oocyte collection. One to 4 embryos were transferred
      to the uterus 1 to 4 hours later. Twenty-four clinical pregnancies were
      established (27.3%) and the implantation rate was 15.3% (38/248). These results
      were both significantly higher than those for our conventional IVF-ET (22.0%
      pregnancy rate and 10.7% implantation rate) (p < 0.05). Eleven babies have been
      born normally and there are 16 current pregnancies. These preliminary findings
      suggest that AHA might be beneficial for patients in whom conventional IVF-ET had
      repeatedly failed.

PMID- 7814930
TI  - [Efficacy and endocrinological analysis of combined buserelin-pure FSH-hCG
      therapy in patients with polycystic ovary syndrome].
AB  - The study was designed to investigate the efficacy of combined buserelin-pure FSH
      hCG therapy in patients with polycystic ovary syndrome (PCO) and to analyse its
      underlying hormonal changes. Buserelin was intranasally administered daily to 13
      patients (35 cycles) for 4-10 weeks with a mean week of 5.4 +/- 1.6 (SD),
      followed by concomitant pure FSH administration. Out of the 13 patients, 8 were
      the ones who had experienced ovarian hyperstimulation syndrome (OHSS) using pure
      FSH alone. Hormonal analyses were performed on these 8 patients. This combined
      regimen resulted in a 97.1% ovulation rate (34/35) and a 37.1% incidence rate of
      OHSS (13/35). In 4 out of the 8 patients who had experienced OHSS, no OHSS was
      observed in the first cycle of the therapy. Eight patients became pregnant with
      the therapy. Excluding one patient whose husband had oligozoospermia, 7 patients
      conceived at the first cycle of the therapy and the pregnancy rate per cycle was
      25.0% (7/28). No abortion or multiple pregnancy was observed in any of the 8
      cases. Pretreatment with buserelin resulted in significantly decreased serum LH,
      FSH, LH/FSH ratio, estradiol (E2), testosterone (T), and androstenedione (ASD).
      Serum E2, T and ASD levels at both preovulatory and midluteal phases were
      significantly lower with the combined regimen than with pure FSH alone. These
      results indicate that this combined regimen improves the characteristic endocrine
      profile of PCO and enables pure FSH to achieve ovulation regularly with a high
      pregnancy rate, although it does not always inhibit OHSS.

PMID- 7814931
TI  - [Maternal serum type III procollagen peptide (P-III-P) and 7S domain of type IV
      collagen (7S) as indicators of placental damage caused by toxemia of pregnancy].
AB  - By means of immunohistochemical techniques, we studied the localization of type
      III and IV collagen in normal and toxemic placentas. We also studied the maternal
      serum levels of type III procollagen peptide (P-III-P) and type IV collagen 7S
      domain (7S) in non-pregnant women, normal term women and cases toxemia of
      pregnancy. Immunohistochemical studies revealed that type III collagen exists in
      the connective tissues composing the villous core and type IV in the basement
      membranes of trophoblast cells and fetal vascular elements. Even in normal
      appearing toxemic placenta, the amount of type III and IV collagen appeared to be
      increased compared with that in normal term placenta, but the amount of type III
      and IV collagen appeared to be decreased in the necrotized chorionic villi of
      severe toxemia. Measurement of the collagen-related substances revealed that
      those levels in toxemic pregnancy were much higher than those in normal term
      pregnancy. In toxemic pregnancy, the incidence of IUGR in the high P-III-P level
      group was increased significantly, and increased more apparently in both the high
      P-III-P and 7S groups. We believe that our data support our that P-III-P and 7S
      in maternal serum flow from the necrotized chorionic villi into the intervillous
      space, and that these measurements are significant indicators of placental damage
      caused by toxemia of pregnancy.

PMID- 7814932
TI  - [Treatment of stage Ia ovarian cancer].
AB  - Ninety-six patients with primary ovarian cancer were treated at Tsukuba
      University Hospital between 1984 and 1992. For all of these patients except stage
      IV, surgical treatment including pelvic and paraaortic lymphadenectomy was
      employed to confirm the clinical stage exactly. Re-staging laparotomy was
      performed in cases with an incomplete initial operation. In thirty cases the
      primary tumors were truly confined to the unilateral ovary (stage Ia). In six
      patients, though the tumor appeared to be confined to the unilateral ovary
      macroscopically at the time of the operation, the stage changed to Ic in one
      case, IIa in one case and IIIc in 4 cases as found by postoperative confirmation.
      The most common tumor in stage Ia was mucinous cystadenocarcinoma. In 23 patients
      with stage Ia, histological grading could be obtained. Twenty-one cases were low
      potential malignancy or grade 1, whereas grade 3 was found in only one case.
      None, except one case diagnosed as stage Ia, has had a recurrence in spite of the
      absence of adjunct therapy, but one patient with grade 3 endometrioid carcinoma
      died of the disease 10 months after staging laparotomy. In conclusion, even
      though the tumor appears to be confined to one ovary, a staging laparotomy should
      be conducted in all patients. When the tumor is proved to be limited to only one
      ovary and is also histologically confirmed to be less than grade 3, it is
      considered that no further treatment is necessary.

PMID- 7814933
TI  - [The effects of sex steroid hormones, gonadotropins, and gonadotropin releasing
      hormone agonist on the proliferation of ovarian cancer cell line (KOC-2S)].
AB  - The present study was designed to determine the effects of sex steroid hormones
      (estradiol, progesterone), gonadotropins (FSH, hCG), and gonadotropin releasing
      hormone agonist (GnRHa: Buserelin) on the proliferation of the ovarian serous
      adenocarcinoma cell line KOC-2S in vitro. The results showed: 1. The colony
      formation rate and fraction growth in the colony stem cell assay were suppressed
      by estradiol (5,000 pg/ml) and progesterone (50 ng/ml). The colony formation
      rates were 2.96% (control); 2.49%, 0.99% (estradiol: 500 pg/ml, 5,000 pg/ml);
      2.58%, 0.53% (progesterone: 5.0 ng/ml, 50.0 ng/ml); 4.80%, 3.34% (hCG: 10 mIU/ml,
      100 mIU/ml); and 1.79%, 2.96% (GnRHa: 1.0 ng/ml, 10 ng/ml). 2. The doubling time
      (DT) in the growth inhibition test was shortened by FSH and the saturation
      density (SD) became greater. The SD was suppressed by hCG. 3. The cytogenic
      features of the cells treated with FSH, estradiol and GnRHa did not show obvious
      morphologic change. The spontaneous floating cells were observed following
      treatment with progesterone. Cytoplasmic enlargement was observed following
      treatment with hCG. 4. Neither erb B nor erb B-2 was expressed in KOC-2S cells,
      and neither was induced by sex steroid hormones, gonadotropins or GnRHa.

PMID- 7814934
TI  - [Retrospective analysis of relationship between progression and regression of
      dysplasia and existence of HPV DNA by in situ hybridization].
AB  - We investigated the relationship between the progression and regression of
      cervical dysplasia and the existence of HPV DNA. The materials we analyzed were
      80 biopsied specimens obtained from 22 cases of dysplasia which were followed-up
      for a long time at our out-patient clinic, and 47 specimens of squamous cell
      carcinoma. Detection of HPV DNA was done by in situ hybridization with
      biotinylated HPV DNA probes types 6/11, 16/18 and 31/33/35. The analysis of
      several specimens obtained at long term follow-up showed that the dysplasia
      progression group had a higher incidence and more frequent detection of HPV DNA
      than the regression group. In the progression group, HPV 16/18 were detected more
      frequently than HPV 31/33/35 at the dysplasia lesion, but HPV 6/11 was detected
      in neither the dysplasia nor the squamous cell carcinoma. Fourteen of the 47
      cases of squamous cell carcinoma (29.8%) were positive for HPV DNA, and 13 of
      them (92.9%) were detected in the lesions of dysplasia adjacent to carcinoma in
      situ or invasive cancer. Comparison of the detection rate for HPV DNA was done in
      the 3 dysplastic areas, i.e. the dysplastic areas in the dysplasia progression
      group (A), dysplasia regression group (B) and in the area adjacent to squamous
      cell carcinoma (C). The detection rates for HPV DNA were 43.5% in A, 27.7% in C
      and 15.0% in B. From these results we drew the following conclusions: 1) The
      continuous existence of HPV DNA, especially type 16/18 in the dysplasia lesions,
      may progress from lesions to carcinoma in situ or invasive cancer.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7814935
TI  - [Scanning electron microscopic study on pathogenesis of peritoneal
      endometriosis].
AB  - To investigate the pathogenesis of peritoneal endometriosis, the morphology of
      peritoneal endometriosis was studied by scanning electron microscopy (SEM) and
      light microscopy (LM). After taking biopsies from peritoneal lesions which were
      suspected of being endometriosis during laparoscopy, the peritoneal surfaces of
      specimens were studied by SEM. Subsequently, for histologic examination of SEM
      findings, some SEM blocks were embedded in Epon, and LM observation of sections
      of Epon-embedded SEM blocks was done. In SEM observations, no ciliated cells were
      observed on the surface of peritoneal endometriotic lesions, but domed cells were
      observed in 17 of 44 specimens and surface configurations were cobblestonelike in
      appearance. In combined observation with SEM and LM, they were suspected of being
      epithelioid-changed mesothelial cells. On the cellular surface, folds, hollows
      and apocrine secretion (one SEM block) were observed. Furthermore, the peritoneal
      surface structure which covered these epithelioid-changed mesothelial cells was
      not always flat, but sometimes invaginations and glandular opening-like
      structures were observed on them. These changes in mesothelial cells and the
      peritoneal architecture may reflect the process of transdifferentiation to
      mullerian epithelium and support the metaplastic theory of the pathogenesis of
      endometriosis.

PMID- 7814937
TI  - [Expressions of Le(y) antigen and PCNA antigen in the normal trophoblast-
      immunohistochemical study with the monoclonal anti-PCNA and Le(y) antibodies].

PMID- 7814936
TI  - [Calcitonin physiologically regulates the postmenopausal bone loss and possibly
      inhibits the bone loss in fast losers].
AB  - To study the correlation between the basal serum calcitonin level and L2-4 bone
      mineral density (BMD), a cross sectional study of 384 healthy subjects (106
      premenopausal, 88 perimenopausal and 109 postmenopausal subjects) and a
      longitudinal study of 42 oophorectomized subjects were conducted. A positive
      correlation was found in perimenopause (r = 0.219, p = 0.040) but not in
      premenopause (r = 0.069, p = 0.4898) and postmenopause (r = 0.141, p = 0.0554) in
      a cross sectional study. The percent reduction in L2-4BMD compared to the
      baseline also correlated with preoperative calcitonin levels at 6 months after
      oophorectomy (r = 0.333, p = 0.0442), but not significantly at 12 months (r =
      0.224, p = 0.27). These data suggest that the basal calcitonin level correlates
      to L2-4BMD only at perimenopause or in the early postoophorectomized period when
      bone turnover is accelerated and bone resorption seems to be faster than bone
      formation. In addition the premenopausal basal calcitonin level may be an
      indicator of the fast loser after menopause.

PMID- 7814939
TI  - [Interstitial irradiation for recurrent leiomyosarcoma in the vagina using the
      template technique].

PMID- 7814938
TI  - [Treatment of genital condyloma acuminatum and vaginal intraepithelial neoplasia
      (VAIN) with topical idoxuridine and acrarubicin].

PMID- 7814940
TI  - [A case of paraneoplastic neurological syndrome associated with carcinoma of the
      uterine cervix].

PMID- 7814941
TI  - [Mechanism of kidney disorders due to nephrotoxic substances].

PMID- 7814943
TI  - [Prevention and therapy of kidney diseases caused by nephrotoxic substances].

PMID- 7814944
TI  - [Kidney diseases caused by antibiotics].

PMID- 7814945
TI  - [Kidney disorders caused by antineoplastic agents].

PMID- 7814942
TI  - [Early diagnosis of kidney disorders induced by nephrotoxic substances].

PMID- 7814946
TI  - [Kidney disorders induced by non-steroidal anti-inflammatory agents and
      immunomodulators].

PMID- 7814947
TI  - [Kidney diseases caused by contrast media and narcotics].

PMID- 7814948
TI  - [Kidney diseases caused by heavy metals].

PMID- 7814949
TI  - [Kidney disorders caused by organic toxic substances].

PMID- 7814950
TI  - [Kidney disorders caused by biological poisons].

PMID- 7814952
TI  - [Kidney disorders caused by endogenous hemoglobins and myoglobins].

PMID- 7814951
TI  - [Kidney disorders caused by bacterial toxins].

PMID- 7814953
TI  - [Kidney disorders caused by endogenous paraproteins and cryoglobulins].

PMID- 7814954
TI  - [Kidney diseases caused by hypercalcemia, hyperuricemia, hyperoxaluria and
      hypokalemia].

PMID- 7814956
TI  - [Early diagnosis and prevention of toxic nephropathies. Discussion].

PMID- 7814955
TI  - [Kidney diseases caused by metabolic disorders of carbohydrate and lipids].

PMID- 7814957
TI  - [Case of hypertrophic meningitis with vasculitis syndrome].

PMID- 7814958
TI  - [Subacute cutaneous lupus erythematosus with positive anti SS-B antibody in the
      aged].

PMID- 7814959
TI  - [Case of peripheral nerve disease due to vitamin E deficiency].

PMID- 7814960
TI  - [Case of protein-losing enteropathy treated with resection of the legion].

PMID- 7814961
TI  - [Case of Ehlers-Danlos syndrome with giant cavernous hemangioma and Klippel-Weber
      syndrome].

PMID- 7814962
TI  - [Fatal case of pheochromocytoma crisis evoked by mycoplasma pneumonia].

PMID- 7814963
TI  - [Case of subclinical sicca with acute pancreatitis and insulin dependent diabetes
      mellitus].

PMID- 7814964
TI  - [AIDS and lung diseases--special reference to Pneumocystis carinii pneumonia].

PMID- 7814965
TI  - [Molecular biology and diagnosis of hepatocellular carcinoma].

PMID- 7814966
TI  - Radiation-induced apoptosis in sensitive and resistant cells isolated from a
      mouse lymphoma.
AB  - Cells were isolated from a mouse lymphoma (LY-TH) and grown in vitro. They were
      susceptible to radiation-induced apoptosis after low doses with the appearance of
      endonucleolytically fragmented DNA 1 h after irradiation. Four hours after
      receiving 5 Gy, 80% of the DNA was endonucleolytically cleaved. Apoptosis
      induction by DNA double-strand break (dsb) formation was more effective compared
      with induction by single-strand break (ssb) formation. After long-term culturing,
      LY-TH cultures became refractory to apoptosis. Apoptosis-permissive cells (LY-as,
      cloned from LY-TH cells) were three times more radiosensitive than clonally
      expanded apoptosis-refractory cells (LY-ar). Low dose-rate irradiation and
      maintenance at 25 degrees C for 5 h postirradiation was sparing in LY-ar but not
      LY-as cells, suggesting a repair deficiency in LY-as cells. Analysis of dsb
      rejoining kinetics revealed no difference in the initial phase of dsb rejoining.
      After 1 h, however, relative dsbs in the LY-as variant increased as
      endonucleolytic cleavage was initiated. Signalling for radiation-induced
      apoptosis in LY-as cells was independent of the DNA dsb repair pathway and
      appeared determined by initial events, whereas in LY-ar cells, because of an
      inhibition in the apoptotic pathway, survival was enhanced and modifiable by
      repair processes.

PMID- 7814967
TI  - Monte Carlo simulation of DNA strand breaks induced by monoenergetic electrons
      using higher-order structure models of DNA.
AB  - A new theoretical model for estimating yield of initial DNA strand break induced
      by several monoenergetic electrons is presented. It is based on the Monte Carlo
      track structure simulation and on new DNA structure models (one turn of double
      strand DNA, nucleosome, solenoid), and links physical and chemical stages of
      radiation action. Direct and indirect effects are strictly distinguished. Some
      results of calculations indicated: (1) the number of single strand breaks per
      nucleus (6 microns in diameter) per Gy in pure water was about 10 times that in a
      cell environment (OH radical life time is assumed to be 8.7 ns). This is due to
      the difference in the time-dependent variation in the total number of the OH
      radical; and (2) the contribution of indirect effects to total damage decreased
      as the order of the DNA target model structure used in the stimulation increased
      (e.g. a one-turn model of double-strand DNA, approximately 98.4%; but the 30-nm
      solenoid model, approximately 86.1%). This was due to the protective effect of
      histone protein against OH radical attack. Double-strand breaks were scored if
      two single-strand breaks were located on the same base pair. The present study
      indicated that the information from morphological and biochemical examinations of
      the cell environment must be considered more carefully with computer simulation.

PMID- 7814968
TI  - Reaction of cysteamine with individual DNA base radicals in gamma-irradiated
      nucleotides at low temperature.
AB  - An ESR investigation of the individual DNA base radicals produced by gamma
      irradiation of frozen solutions of the nucleotides TMP, dCMP, dGMP and dAMP and
      their reactions with cysteamine upon annealing is reported. The results show that
      water radicals in bulk ice do not lead to the formation of DNA or cysteamine
      radicals. Radicals from the oxidation pathway which include the DNA base one
      electron oxidized radicals and their successors, G(C8)OH., A(C8)OH. and thymine
      dimers (.Tdi) and/or T(C6)OH; readily react with cysteamine to form RS. and
      ultimately RSSR-. Reactions of dGMP and dCMP radicals from the oxidation pathway
      with cysteamine occur at lower temperatures than those of dAMP and TMP,
      suggesting hole migration. Both T(C6)H. and C(N3)H. react with cysteamine to form
      RS. and diamagnetic products, but G(C8)H. and A(C8)H. do not. Subtraction of the
      anion radical T-. and its proton adduct T(C6)H. from the total radical yield of
      TMP (with or without cysteamine) suggests that somewhat less than half of the
      total TMP radicals found are a result of the oxidative pathway. Similar results
      are found in the other nucleotides. The total spectral intensity derived from the
      radicals from the oxidative pathway such as G(C8)OH., A(C8)OH. and .Tdi/T(C6)OH.
      are somewhat less than that for the protonated anion radicals. Only one non-base
      radical is identified, a sugar radical at the C(1)' site on the deoxyribose
      portion of dAMP. This species, S(A)., is also found to react with cysteamine or
      its disulfide radical anion. Analyses performed in the presence and absence of a
      thiol are found to allow for a clear separation of oxidative and reductive
      pathways.

PMID- 7814969
TI  - Induction and repair of DNA base damage studied in X-irradiated CHO cells using
      the M. luteus extract.
AB  - DNA base damage was measured in Chinese hamster ovary cells X-irradiated under
      aerobic conditions using an extract of the bacterium Micrococcus luteus. The
      glycosylases and endonucleases present in this extract recognize damaged bases
      and convert them into strand breaks (termed endonuclease-sensitive sites, enss).
      Strand breaks were detected by the alkaline unwinding technique. The induction of
      enss was measured for X-ray doses ranging up to 45 Gy. The relative frequency of
      all enss related to all radiation induced strand breaks was 1.7 +/- 0.4. Repair
      of enss was studied for a radiation dose of 45 Gy. The number of enss was found
      to decrease exponentially with time after irradiation with a half-time of tau
      enss = 37 +/- 8 min. The repair kinetics that were also measured for all X-ray
      induced DNA strand breaks were found to consist of three phases: fast,
      intermediate and slow. The intermediate phase was fitted under the assumption
      that this phase results from the formation and repair of secondary single-strand
      breaks generated by enzymatic incision at the sites of base damage repair. The
      relative frequency of base damage derived from this fit was 1.8 +/- 0.5 and the
      half-time of base damage repair was tau in = 32 +/- 6 min. The agreement of this
      half-time with the half-time obtained when base damage was measured directly
      using the M. luteus assay gives support to the interpretation that the
      intermediate phase of the total repair curve represents the kinetics of secondary
      strand breaks resulting from base damage by enzymatic incision.

PMID- 7814970
TI  - DNA strand scission and base release photosensitized by metallo-phthalocyanines.
AB  - Photoirradiation of aqueous solutions of DNA in the presence of Al- or Zn
      tetrasulphonated phthalocyanines (AIPcS4 and ZnPcS4) causes formation of strand
      breaks and liberation of nucleobases. The effect of added D2O, which enhances
      singlet oxygen (1O2) lifetime, radical scavengers including alcohols and the spin
      trap DMPO, as well as superoxide dismutase, indicates that both singlet oxygen
      (1O2) and free radicals contribute to the production of strand breaks. However,
      in the case of base release, only free radicals, such as the hydroxyl radical
      (.OH), appear to be involved in the degradation process. Detection of the
      characteristic free-radical oxidation products of deoxyribose provides evidence
      that .OH are involved in the photosensitized DNA damage. EPR and spin trapping
      data suggest that superoxide (O2.-) is the most likely precursor of .OH and a
      Fenton-type mechanism is proposed for their formation.

PMID- 7814971
TI  - Radiosensitizing and cytotoxic properties of DNA targeted phenanthridine-linked
      nitroheterocycles of varying electron affinities.
AB  - 2-Nitroimidazoles targeted to DNA via intercalation have previously been shown to
      be as much as 10-100 times more efficient on a molar basis than the untargeted
      nitroimidazole, misonidazole, in vitro as hypoxic cell selective radiosensitizers
      and cytotoxins based on extracellular concentrations. In this work the effect of
      varying the nitroaromatic group has been examined through the preparation of a
      DNA-targeted 4-nitroimidazole (4-MeNLP-3), a 5-nitroimidazole (5-NLP-3) and a 5
      nitrofuran (FEP-2) linked to phenanthridinium ions. With the previously
      synthesized 2-nitroimidazoles, this provides a series of DNA targeted compounds
      of varying electron affinity as well as structure at the nitroaromatic position.
      The present series of compounds was tested for partition coefficient, DNA binding
      ability, reduction potentials and in vitro radiosensitizing and cytotoxic
      abilities. The 4-nitro compound displays good radiosensitizing ability, with an
      SER of approximately 2, despite its low reduction potential, -551 mV. However,
      hypoxia selective toxicity is lost at the lower reduction potentials presumably
      due to redox-independent mechanisms. The results obtained indicate that targeting
      such compounds to DNA diminishes the dependency of radiosensitizing and cytotoxic
      properties on reduction potential and may allow significant uncoupling of
      toxicity from radiosensitizing ability.

PMID- 7814972
TI  - Influence of X-rays on early response gene expression in rat astrocytes and brain
      tumour cell lines.
AB  - The effects of ionizing radiation on c-fos, c-jun and jun-B mRNA levels were
      determined in cultures of rat perinatal type 1 astrocytes and two rat brain
      tumour cell lines, 175A and 9L. In astrocyte cultures X-ray doses as low as 1 Gy
      induced the expression of c-fos and jun-B but had essentially no effect on c-jun.
      The maximum increase in expression was found 1 h after irradiation, which then
      rapidly returned to control levels. These findings suggest that astrocytes may
      play a role in mediating the radiation response of the central nervous system via
      X-ray-induced changes in gene expression. In contrast, doses of up to 20 Gy had
      no effect on c-fos, c-jun and jun-B mRNA levels in the two brain tumour cell
      lines. In addition, whereas 12-O-tetradecanoylphorbol-13-acetate induced the
      expression of these genes in astrocytes, it had little or no effect on fos or jun
      expression in 9L or 175A cells. These results suggest that the signal
      transduction pathways mediating radiation-induced gene expression may be
      different in normal astrocytes and brain tumour cells.

PMID- 7814973
TI  - Distribution of radiation-induced G1 exchange and terminal deletion breakpoints
      in Chinese hamster chromosomes as detected by G banding.
AB  - A total of 255 chromosomal aberrations induced by X-rays in G1 phase of the cell
      cycle were scored in 600 G-banded metaphases prepared from Chinese hamster female
      cells. On the basis of a detailed analysis of these aberrations a total of 441
      chromosomal breakpoints were mapped to the individual Chinese hamster chromosomes
      and their bands. More breakpoints were mapped to G-light (80.5%) than to G-dark
      (19.5%) bands. Chromosomal distribution of breakpoints revealed that chromosomes
      5 and 8 had significantly more exchange breakpoints than expected on the basis of
      chromosomal length, whereas the X chromosome had significantly more terminal
      deletion breakpoints than expected. At the same time chromosomes 5 and 8 had a
      deficiency of terminal deletions, whereas the X chromosome had significant
      deficiency of exchange breakpoints. These results indicate that radiation-induced
      exchange and terminal deletion breakpoints, as observed in the first
      postirradiation metaphase, have different patterns of distribution in Chinese
      hamster chromosomes. Clustering of terminal deletions in the long arms of X
      chromosomes, which are entirely occupied by heterochromatin, suggests that
      chromosomal repair mechanisms responsible for rejoining of chromosomal breaks are
      less effective in heterochromatic than in other genomic regions.

PMID- 7814974
TI  - Radiation-induced transformation of SV40-immortalized human thyroid epithelial
      cells by single and fractionated exposure to gamma-irradiation in vitro.
AB  - Radiation-induced transformation of a human thyroid epithelial cell line (HTori
      3) has been investigated following exposure to single and fractionated doses of
      gamma-irradiation. The human epithelial cells were irradiated in vitro and
      following passaging, transplanted to the athymic nude mouse. Following a single
      exposure to gamma-irradiation in the range 0.5-4 Gy, 22 tumours were observed in
      45 recipients and following three equal fractions in the range 0.5-4 Gy per
      fraction, 18 tumours were observed in 31 recipients. Tumours were
      undifferentiated carcinomas and were observed from 7 to 20 weeks after
      transplantation. They occurred after similar radiation doses to those received by
      the children in the Belarus region of Ukraine, who developed thyroid tumours. The
      number of tumours observed, in each group receiving cells irradiated with a
      single dose of gamma-irradiation in the range 0.5-4 Gy, was similar. Cell lines
      were established from some tumours and the tumorigenicity confirmed by
      retransplantation. These tumour cell lines were more radiosensitive than the
      human thyroid epithelial cell line they were derived from. This indicates that
      transformed cells were not being selected from a subpopulation within the parent
      cell line but that radiation-induced transformants were being induced de novo.
      The human origin of the tumours was established by karyotyping,
      immunocytochemical demonstration of human epithelial cytokeratins and p53
      analysis. DNA fingerprinting confirmed that the tumours were derived from the
      original cell line. Human epithelial cells have proved difficult to transform by
      exposure to radiation. This human thyroid epithelial cell line can be transformed
      by single and fractionated doses of gamma-irradiation and promises to be a useful
      model for studying the mechanisms of radiation-induced transformation of human
      epithelial cells.

PMID- 7814975
TI  - Differences in radiosensitivity of the respiratory burst generated in HL-60 cells
      via different signal transduction pathways.
AB  - Induced differentiation of the promyelocytic leukaemia cell line, HL-60, is
      associated with the acquisition of functional properties, like the expression of
      specific receptors and the competence to exert the respiratory burst (RB). In
      this system we evaluated the effects of ionizing radiation on the signal
      transduction processes involved in the activation of the respiratory burst/NADPH
      oxidase. HL-60 cells were X-irradiated with up to 1 Gy and induced towards
      granulocytic differentiation by treatment with 1.25% DMSO on day 0. The
      expression of the formyl peptide receptor (FPR), the development of
      responsiveness of the cells to its ligand (f-MLP) and to 4 beta-phorbol 12
      myristate 13-acetate (PMA) were measured up to day 7 postinduction/irradiation.
      Using flow cytometry, fluorescinated formyl-hexapeptide or unlabelled f-MLP as
      ligands and dihydrorhodamine 123 (DHR 123) as an indicator of RB activity,
      respectively, the acquisition of functional responsiveness to both stimuli was
      determined. Immature FPR were identified at day 2 after induction which responded
      to the agonist from day 3 on. F-MLP receptor-mediated RB oxidase activation was
      completely radioresistant to 1 Gy, while protein kinase C (PKC)-stimulated
      triggering of the enzyme via PMA was inhibited by about 50% by 0.5 and 1.0 Gy. We
      conclude that different signal transduction pathways as triggered by f-MLP and
      PMA respectively exhibit differences in radiosensitivity, with PKC subspecies and
      downstream responses being possible sites of radiation damage.

PMID- 7814976
TI  - Effects of the protein kinase C stimulant bryostatin 1 on the proliferation and
      colony formation of irradiated human T-lymphocytes.
AB  - The protein kinase C stimulant bryostatin 1 (Bryo) was used in examining human
      peripheral blood T-lymphocyte radiosensitivities in proliferation assays. Bryo
      was similar to PMA in inducing T-cell proliferation by the CD3, CD28 and CD69
      pathways. No difference in radiosensitivities was observed in T-cells stimulated
      by the three independent surface antigen-mediated activation pathways. CD3 was
      chosen as the second signal for comparing the potencies of the three different
      first signals Bryo, phorbol 12-myristate, 13-acetate (PMA), and interleukin 2 (IL
      2) in stimulating T-cell proliferation and in maintaining this response after
      radiation. Though there were radioresponse differences among various individuals,
      the irradiated lymphocytes consistently showed significantly greater
      proliferation when treated with Bryo or PMA than with IL-2 (p < 0.05- < 0.005).
      No difference in proliferative responses was observed in T-cells irradiated
      between 4 h before and 15 h after the addition of stimulants. Colony forming
      assays showed higher colony survival for irradiated T-cells stimulated with Bryo
      than with PMA. These results support the important role of protein kinase C in T
      cell radiation responses, and suggest a potential role for Bryo in enhancing T
      lymphocyte survival during radiation therapy.

PMID- 7814977
TI  - Variable expression of IL-1 beta has minimal effect on the radiation sensitivity
      of three human glioma cell lines.
AB  - Interleukin 1 (IL-1) has been reported to act as a radioprotector in vivo. Data
      from our laboratory and from other investigators suggest that glioma cell lines
      can produce bioactive cytokines including IL-1 and also express IL-1 receptors.
      In view of the putative radioprotective effect of this cytokine, we have examined
      the in vitro radiosensitivity of three human glioma cell lines with widely
      varying levels of endogenous IL-1 beta. The data reveal that when irradiated (2
      Gy/min) as confluent cultures (conditions optimal for differential IL-1 beta
      expression), and plated for colony formation after postirradiation holding, cell
      survival was not correlated with level of IL-1 beta mRNA expression in the two IL
      1-expressing cell lines. However, this was not correlated with a further
      reduction in radiosensitivity. These data indicate that IL-1 beta does not act as
      an endogenous radioprotector in these cells under these experimental conditions.

PMID- 7814978
TI  - Effects of irradiation on cholinergic neurons and nerve growth factor mRNA in
      mouse foetal brain aggregation cultures.
AB  - Neurochemical and morphological markers were used to study the dose-response
      relationship and effects of different doses (0.5, 1.0 and 2.0 Gy) of X
      irradiation on foetal brain cells in reaggregating cell cultures. Cells, prepared
      from mouse forebrain were irradiated on culture day 2, corresponding to embryonic
      day 16 in vivo. The cell reaggregates were monitored continually up to day 40 in
      vitro. The level of a neuronal marker for cholinergic neurons, namely
      acetylcholine esterase (AChE), increased linearly with the dose of irradiation
      after 10 days in vitro. Furthermore, by day 30 the activity of AChE had decreased
      to a level below that found in the control aggregates. In the 2-Gy treatment the
      level of choline acetyltransferase (ChAT), another cholinergic-neuron marker,
      increased during the first 20-30 days in culture but had declined to control
      levels by day 40. Using Northern blot analysis of total RNA prepared from these
      cell reaggregates, we determined relative changes in the level of expression of
      mouse nerve growth factor (NGF) mRNA subsequent to irradiation after 10 and 30
      days in culture. The ratio between the level of expression of NGF and that of
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was calculated and it was found
      that by day 10 in vitro the level of NGF had increased compared with control
      levels, in a dose-related manner. After 30 days in culture, the level of NGF mRNA
      was still high after the low-dose (0.5 Gy) treatment, whereas it had decreased
      below control levels after the higher-dose (1.0 and 2.0 Gy) treatment. The
      aggregates showed a tendency to deform and fuse together after irradiation:
      furthermore, the number of aggregates occurring as two or more grown together,
      increased with the X-ray dose. Aggregate size decreased with time in vitro and
      with irradiation dose. Thus, we showed that cholinergic and morphological markers
      are affected by irradiation and the alteration in AChE activity induced by
      irradiation correlated well with the changes in NGF mRNA.

PMID- 7814979
TI  - Effectiveness of radon relative to acute 60Co gamma-rays for induction of
      micronuclei in vitro and in vivo.
AB  - Because radon and its progeny (referred to collectively here as radon) emit alpha
      particles with a wide range of energies, as well as beta particles and gamma
      rays, it is important to quantitate the relationship between initial damage
      induced by radon and that by acute low-LET radiation. We have evaluated dose
      response relationships for induction of micronuclei both in vivo and in vitro
      following exposure to radon or 60Co. To determine if isolation procedures altered
      the cells' responsiveness to 60Co gamma-ray exposures, animals were exposed
      before cell isolation, or cells were isolated and then exposed. The data were
      described by linear dose-response functions and were not significantly different
      when the radiation exposure was in vivo or in vitro (respectively
      micronuclei/1000 binucleated cells = 1.6 +/- 6.5 + 62 +/- 2.7 D; micronuclei/1000
      binucleated cells = 15.4 +/- 26.0 + 54.6 +/- 11.4 D, where D is in Gy). Primary
      rat lung fibroblasts (RLF) or Chinese hamster ovary (CHO-K1) cells were exposed
      in vitro to either radon or 60Co gamma-rays. Radon was 10.9 +/- 2.6 and 12.5 +/-
      2.4 times as effective per Gy of radiation dose in producing micronuclei as was
      60Co in RLF and CHO-K1 cells respectively. To determine the relative biological
      effectiveness of in vivo radon exposure, animals were exposed to either radon or
      60Co, and lung fibroblasts were isolated and evaluated for radiation-induced
      micronuclei. In vivo radon exposure was 10.6 +/- 1.0 times as effective as acute
      whole-body 60Co exposure in producing micronuclei in lung fibroblasts. Different
      cell lines and exposure conditions resulted in similar effectiveness factors.
      Such ratios help evaluate the biological damage, hazard and risk associated with
      radon inhalation.

PMID- 7814980
TI  - Placental transfer of ruthenium in rat and guinea-pig.
AB  - Ruthenium-106 in citrate solution was administered intravenously to rat at
      different stages of pregnancy and to guinea-pig either before conception or in
      late pregnancy. The results for rat showed that retention in the embryo/foetus
      measured at 3-5 days after administration increased from about 0.0002% of
      injected activity per embryo/foetus on day 12 of gestation to about 0.05% at
      birth. The relative concentrations of 106Ru in embryo/foetus and mother (Cf/Cm
      ratio) were about 0.1 in each case. Concentrations in the yolk sac on day 12 were
      about 1% g-1 compared with 0.01% g-1 in the foetus. Retention in the guinea-pig
      foetus in late gestation at 7 days after administration (days 50-57) was about
      0.2% injected activity per foetus, corresponding to a Cf/Cm = 0.2. Retention in
      each foetoplacental unit was 2% of injected 106Ru with 50% in the yolk sac, 35%
      in the placenta and 10% in the foetus. For administration 4 weeks prior to
      conception, the level of 106Ru retained in the foetus on day 57 of gestation was
      two orders of magnitude lower than after short-term administration, with a Cf/Cm
      about 0.004.

PMID- 7814981
TI  - Spatial distribution of naturally occurring 210Po and 226Ra in children's teeth.
AB  - Deciduous and permanent teeth extracted from juveniles for orthodontic purposes
      have been analysed using alpha-sensitive plastic track detectors for the spatial
      distribution of total alpha-activity and naturally occurring 210Pb-supported
      210Po and 226Ra. The distribution of these radionuclides is non-uniform, with
      210Po being primarily associated with outer enamel and 226Ra with the pulp. The
      observations suggest that 210Pb/210Po concentrates at the interface of enamel
      with saliva or blood, by means of unidirectional ionic exchange with calcium. In
      contrast, 226Ra concentrates in the predentine band at the interface with pulp
      and with systemic blood circulation, where its uptake is permitted by the
      incomplete calcification in this band. Activity concentration was measured in 900
      teeth. Total concentration on the outer enamel surface of deciduous teeth,
      permanent teeth from children < or = 10 years and permanent teeth from children >
      10 years give respective mean values of 8.63 +/- 0.26, 5.76 +/- 0.48 and 7.00 +/-
      0.15 Bq kg-1. 226Ra concentration on the corresponding longitudinal sections
      comprising pulp, dentine and annular enamel give respective mean values of 0.715
      +/- 0.055, 0.418 +/- 0.083 and 0.514 +/- 0.029 Bq kg-1. Mean activity
      concentration in 32 foetal teeth was 2.05 +/- 0.31 Bq kg-1. The results form the
      basis of more detailed studies of (1) age-dependent uptake of alpha-radionuclides
      in teeth and their microdistribution, and (2) the geographical variation in
      activity concentration with respect to environmental factors such as domestic
      radon exposure.

PMID- 7814982
TI  - Obstructive defaecation and slow transit constipation: the proctographic
      parameters.
AB  - Twenty-two patients with functional obstructive defaecation were compared with
      seven patients with slow transit constipation using isotope proctography. The
      obstructive defaecation patients were unable to perform a complete rectal
      evacuation (% of the activity evacuated: 54%). The defaecation time in this group
      was prolonged (120 s) with a lower defaecation rate (0.5%/s) compared with the
      slow transit constipation subjects (32 s and 1.8%/s). The anorectal angle (ARA)
      on straining did not change in the obstructive defaecation patients but became
      more obtuse in the slow transit constipation subjects (P < 0.02). The pelvic
      floor (PF) descent on straining and evacuation was greater in obstructive
      defaecation patients compared with the slow transit constipation ones (P < 0.01).
      Obstructive defaecation is characterised by prolonged defaecation and reduced
      defaecation rate compared with slow transit constipation. Obstructive defaecation
      patients present with more acute ARAs on straining, and abnormal perineal descent
      in contrast to the slow transit constipation ones.

PMID- 7814983
TI  - Enterocele demonstrated by defaecography is associated with other pelvic floor
      disorders.
AB  - Sixty-nine patients with enterocele on defaecography, and 128 patients without
      enterocele but with other abnormal findings were investigated to identify
      concomitant colorectal disorders and their relationship with enterocele. Of the
      69 patients with enterocele, 38 (55%) had concomitant rectal intususception and
      26 (38%) rectal prolapse. Abnormal physiological findings on anorectal manometry
      and electrophysiology were more common in patients with enterocele. Previous
      hysterectomy increased the risk of enterocele formation. The study has
      demonstrated that patients with enterocele should be investigated thoroughly for
      other lesions before treatment is planned. Further investigation of the role of
      enterocele in patients with defaecation disorders is required.

PMID- 7814984
TI  - Ear tumours induced by experimental carcinogenesis in the rat: excision prevents
      early death.
AB  - 1,2-dimethylhydrazine (DMH) is widely used to induce colorectal tumours in
      rodents. Some of the animals develop ear as well as colorectal tumours. Rats with
      large, ulcerated ear tumours are usually sacrificed before the completion of the
      experiment. In this experiment, fourty-six male Spraque-Dawley rats were injected
      with 1,2-dimethylhydrazine (21 mg/kg body weight) once a week for 27 weeks to
      study the histogenesis of colorectal carcinoma. Thirty-six developed ear tumours.
      Fourteen of the 36 tumours were larger than 2 cm in diameter. These developed
      between 20-26 weeks and were surgically excised 1-5 weeks later. Four rats died
      postoperatively. The surgical removal of large ear tumours permitted the
      completion of the large bowel experiment on schedule (i.e. 27 weeks) in 10 (28%)
      of the 36 rats with ear tumours.

PMID- 7814986
TI  - Does laparoscopic-assisted ileal pouch anal anastomosis reduce the length of
      hospitalization?
AB  - Previous data have suggested that laparoscopic colon and rectal surgery may
      shorten the length of hospitalization. These claims have been attributed to a
      reduction of the length of ileus. The definition of "ileus" is variable and in
      all cases is subjective. In this study it was defined as the length of time until
      the patient passed flatus or stool without nausea, vomiting or abdominal
      distention. This prospective study was undertaken to compare the duration of
      ileus and of hospitalization after laparoscopic-assisted (LAC) and standard
      laparotomy (SC). After restorative proctocolectomy with an ileal-pouch anal
      anastomosis (IPAA) in both sets of patients. Twenty-two patients underwent LAC
      and 20 age, sex, and diagnosis-matched controls underwent SC. Mucosal ulcerative
      colitis (MUC) was the diagnosis in 16 LAC and in 15 SC patients while polyposis
      was the diagnosis in 6 LAC and in 5 SC patients. The mean time to resolution of
      postoperative ileus was 4.2 (4-11) days in the LAC group and 3.3 (2-5) days in
      the SC group. Hospital discharge was similar in each group occurring at a mean of
      8.7 (7-13) days after LAC and 8.9 (6-18) days after SC. Neither the length of
      time for ileus resolution nor the length of hospitalization were reduced in the
      LAC group. Laparoscopic-assisted IPAA conferred none of the theoretical
      advantages associated with other laparoscopic procedures.

PMID- 7814985
TI  - Biofeedback re-education of faecal continence in children.
AB  - The purpose of this prospective study was to see if pretreatment anorectal
      motility can predict successful correction of faecal incontinence with
      biofeedback. Forty-seven consecutive children, aged 5 to 18 years, were treated.
      They had been treated for idiopathic constipation with faecal impaction, but had
      remained incontinent (n = 15), had been operated for congenital anorectal
      malformations of high (n = 19) or low (n = 2) type, or had a number of organic
      congenital pelvic abnormalities (n = 11). This consecutive series represents our
      entire experience with biofeedback for faecal incontinence, in the period from
      January 1 1983 to December 31 1989. In each patient, at the first session,
      anorectal manometry was performed. Resting pressures in the rectum, upper anal
      canal and lower anal canal were measured. The threshold of rectal sensation
      during distension, the maximal pressure during voluntary sphincteric contraction
      and the time to half decrease of sphincteric pressure because of muscular fatigue
      were also noted. The patient was then asked to make a voluntary sphincteric
      contraction, while the rectum was being distended with the volume at threshold
      for rectal sensation. In subsequent sessions, the rectum was also distended but
      without warning the patient, who was congratulated when he or she contracted the
      sphincter immediately after onset of rectal distension. Full continence was the
      criterion used to classify re-education as a success. Improvement or no change in
      continence was considered as failure of the treatment.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7814987
TI  - Loop ileostomy fixation: a simple technique to minimise the risk of stomal
      volvulus.
AB  - Turnbull's "loop" ileostomies is a routinely performed procedure in the
      management of a variety of colorectal problems. Mechanical and functional
      complications occur with both permanent and temporary ileostomies, however they
      are more common with the loop than with the end (Brooke) variety. With the advent
      of restorative proctocolectomy with pouch formation, and the documented benefit
      of simultaneous temporary faecal diversion, the incidence of such complications
      will rise. Bowel obstruction, requiring laparotomy in the interval before stoma
      closure, is more commonly associated with the loop ileostomy. A loop stoma is
      routinely brought out directly through the abdominal wall, with little or no
      fixation or closure of the lateral space. However, anti-mesenteric fixation, as
      described here, minimises the risk of volvulus by widening the attachment of the
      adjacent ileum to the parities, creating a broader fulcrum. Since adopting this
      simple technique, we report no complications in over 30 loop ileostomies, "fixed"
      by this technique and followed up for a minimum of 4 years. Where applicable, no
      difficulty was encountered with stoma closure, either by a transverse single
      layer serosubmucosal technique, or as a minimal resection with end to end
      anastomosis (sewn or stapled), following bowel mobilisation. This technique
      should minimise the frequency of obstructive events, and we recommend it's
      routine use.

PMID- 7814988
TI  - Distribution of gelatinase B (MMP-9) and type IV collagen in colorectal
      carcinoma.
AB  - Gelatinase B (92 kD, matrix metalloproteinase-9, MMP-9), an enzyme capable of
      degrading several connective tissue components, was demonstrated by
      immunolocalization in all specimens of colorectal carcinoma (n = 40), but its
      distribution between specimens was variable. MMP-9 expression was more frequently
      observed in advanced tumour stages and was especially prevalent at the side and
      deep margins of the tumours, and ulceration sites. MMP-9 staining was observed
      for transformed epithelial cells, macrophages and neutrophils, but seldom for
      vascular or stromal cells. By contrast, the enzyme was absent from epithelial
      cells of normal mucosal tissue. Immunostaining of type IV collagen, the major
      structural component of basement membranes, revealed a general depletion or loss
      of these structures both within the tumours and at the tumour margins. Dual
      immunolocalization of MMP-9 and type IV collagen demonstrated that MMP-9
      expression at specific sites in the tumour was often inversely related to the
      distribution of type IV collagen. MMP-9 expression was most pronounced at the
      invasive tumour margins and in microfoci where tumour cells were in close
      proximity to inflammatory cells. Such observations support the concept that
      localized proteolytic and collagenolytic activities contribute to the invasive
      properties of colorectal tumours.

PMID- 7814989
TI  - Efficacy of dilatations for anastomotic colorectal stenoses: prognostic factors.
AB  - The authors report their experience of 30 patients with colorectal anastomotic
      stenosis treated by 62 dilatation sessions in order to evaluate which anastomotic
      characteristics could influence the success of dilatation therapy. Patients were
      subdivided into group A (dilatation successful) and group B (dilatation
      unsuccessful). Overall, dilatation was successful in 73.3% of cases, with only
      one important complication. The prognostic factors considered were anastomotic
      dehiscence, adjuvant radiotherapy, presence of colostomy at dilatation, site,
      morphology and length of the stenosis, presence of neoplastic recurrence, type of
      anastomosis and type of dilatation. Radiotherapy, local neoplastic recurrence and
      large anastomotic dehiscence were the more important independent prognostic
      factors. If present together, they were associated with an almost 100%
      probability of failure and, vice versa, if they were absent this probability was
      5%.

PMID- 7814990
TI  - Treatment of high anal fistulae by primary occlusion of the internal ostium,
      drainage of the intersphincteric space, and mucosal advancement flap.
AB  - In a prospective study on 224 patients with so-called high-fistula in ano (189
      transsphincteric, 35 suprasphincteric) the long-term results of a sphincter
      saving operation technique were assessed. The follow-up period was 1 to 7.5
      years. This technique consists of one-stage fistulectomy as well as of drainage
      of the intersphincteric space by internal sphincterotomy. The site of the former
      primary orifice of the fistula is adapted by multiple peranally performed single
      stitches, including mucosal advancement flap distal to the original fistulous
      opening. Postoperatively, 24 cases of suture leakage occurred (9% with the
      transsphincteric and 20% with the suprasphincteric fistula). 27 patients
      developed late complications like fistula recurrences or combinations of fistula
      and anal abscess (10.7% with the transsphincteric and 19.9% with the
      suprasphincteric fistula). Anal manometry was carried out preoperatively as well
      as postoperatively. A significant decrease in the postoperative resting pressure
      compared to the preoperative value was determined. The two fistula groups
      differed statistically both with regard to the resting pressure and the
      contraction pressure. Significant impairment of continence developed in 21% of
      patients with transsphincteric fistula but in 43% of patients with
      suprasphincteric fistula (intermittent fecal spoiling/use of perineal pads). The
      total percentage of complications rose with the number of previous fistula
      operations.

PMID- 7814991
TI  - Prognostic factors for survival in colonic perforation.
AB  - Colonic perforation is an abdominal emergency with high morbidity and mortality.
      This retrospective study was performed to evaluate the prognostic relevance of
      several factors and to characterize patients at high risk. One hundred and twelve
      patients (61 women, 51 men) were treated for colonic perforation from 1979 to
      1992. Diverticulitis [65 patients (58%)] and carcinoma [24 patients (21%)] were
      the commonest pathology. In 62 cases (55%) perforation was found to be covered;
      50 (45%) times it was free. 34 (30%) patients had diffuse peritonitis. Resection
      with primary anastomosis was performed 43 times (7 times with a protective
      colostomy). Resection without restoration of the intestinal continuity was
      carried out 53 times (including 49 Hartmann operations). Suture with drainage was
      performed 16 times mainly after iatrogenic perforation (8 times with a
      colostomy). The overall mortality was 19.6% (22 patients). The prognostic
      importance of various factors was investigated by univariate analysis (Wilcoxon
      and Chi-square test) and stepwise logistic regression including sex, age,
      underlying disease, localization and type of perforation, degree of peritonitis,
      pre- or postoperative organ failure, surgical procedure, reoperation, sepsis and
      the Mannheimer Peritonitis Index (MPI) score. Age over 65 years (relative risk
      4.6, P = 0.0089), organ failure (relative risk 40, P = 0.001) and MPI (relative
      risk for an increase of 10 points 2.72, P = 0.001) proved to be the only risk
      factors of significance. The patient's course is determined by the septic state,
      while the underlying pathology and degree of peritonitis did not significantly
      influence survival.

PMID- 7814992
TI  - Skin cover of perineal defects using V-Y flaps.

PMID- 7814993
TI  - Successful local repair of paracolostomy hernia with a newly developed prosthetic
      device.

PMID- 7814994
TI  - Fluctuations in circulating cell numbers following chemotherapy or bone marrow
      transplant.
AB  - We study the effect of noise on the behaviour of a dynamic cell population model
      in which cell replication and maturation take place simultaneously. We assume
      that the maximum proliferative potential v fluctuates uniformly about a mean
      value of v, and show that a decrease in v and/or the input flux uin into the
      population can lead to an increase in the variance in the cellular efflux uf. We
      draw a qualitative correspondence between this behaviour and the commonly
      observed increase in the variance of circulating blood cell numbers following
      chemotherapy and radiotherapy, both of which lead to a decrease in v and uin, and
      bone marrow transplant which probably corresponds to a decrease in uin.

PMID- 7814995
TI  - Population size dependent incidence in models for diseases without immunity.
AB  - Epidemiological models of SIS type are analyzed to determine the thresholds,
      equilibria, and stability. The incidence term in these models has a contact rate
      which depends on the total population size. The demographic structures considered
      are recruitment-death, generalized logistic, decay and growth. The persistence of
      the disease combined with disease-related deaths and reduced reproduction of
      infectives can greatly affect the population dynamics. For example, it can cause
      the population size to decrease to zero or to a new size below its carrying
      capacity or it can decrease the exponential growth rate constant of the
      population.

PMID- 7814996
TI  - Ethics, politics, and health care reform.

PMID- 7814997
TI  - Strategic compromise: real world ethics.
AB  - In this essay the Co-chair of Ethics Working Group 17 of the Health Care Task
      Force discusses the formation, organization processes and activities of the
      group, and provides an analysis and critique of the experience. It is suggested
      that the creation of the group and its inclusion in the process made a social
      statement which legitimized ethics as a significant part of public policy
      deliberations. At the same time, major questions are raised about the role of
      ethics in public policy arenas in which strategic compromise becomes the order of
      the day. Balanced and objective involvement may be illusory. Ethics, like
      informed consent, is a process, not an event and is ever evolving. Those who
      attempt to bring ethical considerations to the world of public policy have an
      obligation to think carefully about what should constitute an appropriate
      theoretical framework, make efforts to determine what is unique about ethics, and
      consider mechanisms for the various ethics disciplines to work effectively
      together. From this experience, the author developed a personal commitment to
      focus upon the critical importance of universal coverage for all Americans.

PMID- 7814998
TI  - The articulation of values and principles involved in health care reform.
AB  - The Ethics Working Group of Clinton's Health Care Task Force developed a list of
      principles and values that should govern health care reform. These principles and
      values are compatible with central moral and political traditions, as well as
      with more rigorous theoretical accounts of justice and health care, but they are
      "freestanding" points of agreement, not presupposing any particular theoretical
      background. Though imprecise and not ranked by priorities, the principles guide
      thinking about the fairness of alternative reform proposals. Their use is
      illustrated by comparing alternatives on universality of access, phase-in period,
      the creation of unequal tiers, and the provision for wise allocation and
      rationing.

PMID- 7814999
TI  - Just caring: health reform and health care rationing.
AB  - Health reform must include health care rationing, both for reasons of fairness
      and efficiency. Few politicians are willing to accept this claim, including the
      Clinton Administration. Brown and others have argued that enormous waste and
      inefficiency must be wrung out of our health care system before morally
      problematic cost constraining options, such as rationing, can be justifiably
      adopted. However, I argue that most of the policies and practices that would
      diminish waste and inefficiency include implicit (and therefore morally
      problematic) rationing. Critics of rationing see as its most morally and
      psychologically troubling feature that an identified individual is denied
      potentially beneficial care. That psychic anguish may not be eliminable, and
      perhaps ought not be eliminated. But if rationing protocols are fairly adopted
      through a process of free and informed rational democratic deliberation to which
      all have access, the moral objections are largely overcome. Such a process is
      possible only if implicit rationing is recognized and rejected.

PMID- 7815000
TI  - Rationing and the Clinton health plan.
AB  - President Clinton, already facing formidable obstacles in reforming the health
      care system, denies that it will involve any rationing. This is politically
      understandable, but wrong. Infinite needs are rapidly overtaking finite
      resources. Most health providers recognize that the genius of modern medicine has
      outpaced our ability to pay. But the public still has unlimited expectations and
      a blind faith that everything can be provided to everyone by simply eliminating
      "waste, fraud, and abuse." Rationing is inherent in any health care system. As
      government undertakes to define what is "medically necessary or appropriate," it
      will unavoidably undertake a series of rationing decisions. Health care is being
      transformed from a private good to a public good. Government, when it reforms the
      health care system, must inevitably ask: How do we buy the most health for the
      public?

PMID- 7815001
TI  - Of rescue and responsibility: learning to live with limits.
AB  - Universal access to health care is still a dream rather than a reality in the
      United States. This is partly because a rule of rescue, by impelling us to help
      people in need, urges us to ignore the limits of our health care policies
      wherever those limits would adversely affect a given individual. As the rule of
      rescue undermines whatever limits we set on health care entitlements, it can
      thwart the cost containment so essential to expanding access. Rather than accept
      unlimited expense, we have thus far declined to universalize health care. The
      situation is exacerbated by an economic insulation shielding patients and
      physicians from the costs of care, prompting both to regard health care as free,
      an unlimited right. To reverse this costly entitlement mentality and place
      reasonable limits on rescue, patients must exercise greater personal
      responsibility for the costs of their care by directly experiencing some of the
      economic consequences of their health care decisions. Several mechanisms are
      available to accomplish this goal without posing economic barriers to needed care
      or penalizing people for becoming ill.

PMID- 7815002
TI  - Personal freedom and responsibility: the ethical foundations of a market-based
      health care reform.
AB  - The current health care system is not operating with a properly functioning
      market. Health care costs are hidden and often shifted, consumers and providers
      are insulated from the economic consequences of their decisions, and costs
      therefore go up dramatically. Instead of attacking both the structural
      deficiencies and the consequent inequities of the current employer based
      insurance system, the Clinton Plan simply expands them, and adds a heavier level
      of government regulation. The ultimate choice for the public is between a health
      care system based on consumer choice or a government controlled system. In
      pursuing a market based health care reform that enhances personal freedom and
      responsibility, two ethical principles are served. First, American consumers will
      be made aware of the true costs of health care services, and market forces will
      thus introduce incentives on the part of providers to control costs. Second,
      justice will be served; for not only will providers of medial services receive
      their due, but public policy makers can target relief more effectively to those
      who need it most.

PMID- 7815003
TI  - Should we create a health care system in the United States?
AB  - An orthodoxy has arisen which claims that there is a crisis in the United States
      health care system such that the system needs to be reformed. This essay
      challenges that orthodoxy by showing that we do not have a health care system in
      the United States. We have a non-system of health care, just as we do for
      virtually all basic social institutions. Challenging the current orthodoxy
      surfaces two ethical issues that have been ignored: creating a health care system
      will (a) cause resurgent paternalism and (b) pose a threat to moral pluralism.

PMID- 7815004
TI  - Health care reform and abortion: a Catholic moral perspective.
AB  - The Catholic Church in the United States provides extensive health care service
      through its more than 600 health facilities. The Church, on the basis of its
      moral teaching, sees health care as a basic human right and supports universal
      coverage. At the same time, the Church considers abortion morally wrong and
      opposes coverage of abortion as a health service in a national health plan.
      Mandated coverage of abortion would violate the moral commitments of Catholic
      hospitals and the consciences of Catholics who would be required to financially
      support provision of abortion services.

PMID- 7815005
TI  - Health care reform: a study in moral malfeasance.
AB  - Instead of benefitting from open meetings and public discussions, the Clintons
      drafted their health care plan in private and asked that it be accepted in haste.
      They advance an ideology that claims we can receive the best care for all without
      any increase in cost or rationing, and then they use "ethicists" to justify this
      ideology through a supposedly common morality. However, there is no such common
      morality. In the context of American pluralism, one must look to the actual
      consent of the governed and recognize the limits on state authority. The result
      will be a two tiered system of health care, with a basic tier focusing on cost
      effective care for the poor that eliminates suffering rather than equalizing
      inputs, and a space for collateral private insurance.

PMID- 7815006
TI  - Entrainment of reentrant tachycardia in a computer model.
AB  - Capture of the cardiac rate by pacing followed by an immediate return to the
      original rate after pacing has been proposed as characteristic of reentrant
      rhythms. In this study, such entrainment has been demonstrated using computer
      model simulations of propagated excitation and of reentry associated with
      structural and functional obstacles. With structural obstacles, the mechanism of
      entrainment was bidirectional propagation of paced excitation in reentry
      circuits, with collision of the reentrant and paced excitation in one direction
      and continued propagation of paced excitation in the other direction. The time of
      pacing onset, rate, and location all affected the QRS waveform during
      entrainment. With a particular time of onset and rate of pacing, the duration of
      time during which the QRS waveform underwent dynamic change was directly related
      to the distance between the pacing site and reentrant circuit. The location of
      reentry associated with functional obstacles moved so that the relationship
      between pacing-induced and reentrant excitation varied. In some cycles, pacing
      did not alter reentrant circuits, that is, entrainment did not occur, while other
      cycles were entrained, but by a different mechanism than that with structural
      obstacles. Leading circle reentry circuits, consisting of propagation away from
      and returning to reentry sites, did not have an excitable gap and paced
      excitation did not enter those circuits. Paced excitation did, however, enter the
      propagation paths between leading circle reentry circuits and modified the
      circuits by affecting the recovery of excitability.

PMID- 7815007
TI  - Complex dynamic order in ventricular fibrillation.
AB  - Self-sustained circus movement of excitation has long been discussed as the
      underlying mechanism of ventricular fibrillation. This concept now appears to
      have found general acceptance. Mapping studies are very expensive and do not
      permit observations to be isolated from varying external influences. The authors
      have therefore used a simple cellular automation for studying the basic
      principles of excitation spreading during ventricular fibrillation under various
      conditions. Highly ordered spiral waves, described in other computer models,
      previously interpreted as fibrillation were encountered. Comparisons of pseudo
      electrocardiograms created by the cellular automaton with original
      electrocardiographic recordings showed similarity in the time series and in fast
      Fourier transformation. Modulation of refractory times often led to the
      termination of model fibrillation. Clinical evidence suggests that maintenance of
      the 1/f (RR-variability) variations produced by the autonomic nervous system
      exerts a protective effect on the evolution of ventricular fibrillation.

PMID- 7815008
TI  - Role of left ventricular geometry in the alteration of initial QRS vectors due to
      concentric ventricular hypertrophy.
AB  - The relation between serial magnitudes of instantaneous spatial vectors, obtained
      throughout ventricular depolarization, and echocardiographically estimated left
      ventricular (LV) mass was investigated in 64 patients with congenital aortic
      stenosis and in 16 patients with coarctation of the aorta. While the correlation
      was positive between LV mass and vector magnitudes at 50 and 60 ms after QRS
      onset (r = .530 and .557, P < .01), it was found to be negative with regard to
      the magnitude of the initial 10 and 20 ms vectors (r = -.285 and -.355, P < .01).
      Computer simulation of activation propagation in different models of LV
      enlargement has shown that the decrease of the spatial magnitude of initial
      vectors, as well as a marked decrease of the area of the anterior portion of the
      horizontal plane QRS loop and of the Q amplitude of the orthogonal z lead, are
      characteristic of concentric LV hypertrophy with decreased diastolic volume and
      were not observed with unchanged or dilated chamber size. Repeated assessment of
      the magnitude of initial QRS vectors may indicate changes of LV remodeling in
      patients with LV pressure overload.

PMID- 7815009
TI  - QRS alterations in body surface potential distributions during percutaneous
      transluminal coronary angioplasty in single-vessel disease.
AB  - Body surface QRS potentials were recorded with 63 chest leads in 20 patients with
      proximal single-vessel disease located on either the left anterior descending
      coronary artery (n = 10), the right coronary artery (n = 6), or the left
      circumflex coronary artery (n = 4) before, during, and after percutaneous
      transluminal coronary angioplasty. In each case, three consecutive inflations of
      relatively short duration (37 +/- 14 seconds) were carried out. Electrical
      activity was displayed as unipolar electrograms and body surface potential maps.
      The total QRS complex duration decreased in 14 of the 20 patients. Focal
      conduction disturbances were observed in six cases; all six had left anterior
      descending coronary artery occlusion and two were also accompanied by a clear
      shortening of the right epicardial breakthrough time. In these two cases, an
      initial activation loss seemed to be characteristic, whereas in the other four
      cases, a rather diffuse slowing of intraventricular conduction, especially during
      the terminal portion of the QRS, could be observed. Individual and group mean
      isointegral difference body surface potential maps (during-minus-before dilation)
      were considered valuable for the interpretation of localized changes in
      intraventricular conduction during percutaneous transluminal coronary
      angioplasty, and their individual variations could, at least partly, be explained
      by the presence or absence of collateral circulation. Two different hypotheses
      are suggested to account for the QRS complex shortening observed during short
      term myocardial ischemic injury: (1) coronary artery occlusion delayed activation
      of the portion of the septal region that is normally activated early during the
      QRS, and/or (2) coronary artery occlusion increased the speed of propagation
      within the ventricles. Both of these hypotheses are discussed in light of earlier
      clinical and experimental results.

PMID- 7815010
TI  - ECG characteristics of dilated cardiomyopathy.
AB  - To elucidate the electrocardiographic (ECG) characteristics of dilated
      cardiomyopathy (DCM), the authors analyzed the 12-lead ECGs and echocardiograms
      in 45 patients with DCM, 54 patients with left ventricular (LV) dilatation
      secondary to valvular heart disease (VHD), 101 hypertensive patients with LV
      hypertrophy, and 63 normal control subjects. In addition, serial ECG and
      echocardiographic changes in DCM during a mean follow-up period of 1.6 years were
      evaluated. Sokolow's criterion (S wave in lead V1 [SV1] + R wave in lead V5 or V6
      [RV5 or RV6] > 35 mm) was met comparably in patients with DCM (69%), VHD (61%),
      and hypertension (74%) (P = NS). Notably, RV6 in DCM was the highest among the
      four groups and correlated with the degree of LV dilatation. In contrast, the R
      waves in leads I, II, and III (RI, RII, RIII) in DCM were the lowest and were not
      affected by the degree of LV dilatation, although RII and RIII in VHD and RI in
      hypertension correlated with the degree of LV dilatation and hypertrophy,
      respectively. As a result, all voltage ratios of RV6/RI, RII, RIII in DCM were
      not only the highest, but also increased linearly as the LV dilated progressively
      during the follow-up period. In particular, RV6 over the maximum R wave in leads
      I, II, and III (RV6/Rmax) in DCM correlated with the degree of LV dilatation and
      inversely correlated with ejection fraction. Subjects with DCM had a
      significantly higher RV6/Rmax than did patients with VHD, hypertension, and
      normal subjects (3.4 vs 1.7, 1.4, 1.2, respectively; P < .001), and this ratio of
      > or = 3 was seen in 67% of the DCM patients versus 4% of the VHD patients, 1% of
      the hypertensive patients, and 0% of the normal subjects. Thus, DCM commonly
      shows the ECG signs of LV hypertrophy, but characteristically has the high
      voltage ratios of RV6/RI, RII, RIII.

PMID- 7815011
TI  - Analysis of body surface area as a determinant of impedance during radiofrequency
      catheter ablation in adults and children.
AB  - Since most radiofrequency (RF) generators used for catheter ablation approximate
      a constant voltage output, applied power is inversely proportional to the
      impedance load of the system. Knowledge of the expected impedance load for a
      patient may facilitate selection of safer and more effective voltage output.
      Preliminary observations suggest that in adults, impedance is directly
      proportional to body surface area (BSA), thus prompting this study to determine
      whether this relation was maintained in smaller patients undergoing RF catheter
      ablation. Prospective analysis of impedance from 949 RF deliveries in 76 patients
      (BSA, 0.69-2.3 m2) revealed the mean impedance for all deliveries to be 103 +/- 8
      ohms. Two-phase linear regression analysis revealed a significant, direct
      correlation between impedance and BSA in patients with a BSA > or = 1.5 m2 (P =
      .001); however, for patients with a BSA < 1.5 m2 there was no correlation. These
      results indicate that as patient size decreases below 1.5 m2, impedance is
      constant. Radiofrequency catheter ablation procedures in children may require
      selection of a voltage output similar to that used in adults in order to produce
      effective RF lesions.

PMID- 7815012
TI  - Power spectral analysis of heart rate variability as a new method for assessing
      autonomic activity in the rat.
AB  - The authors studied power spectral analysis of heart rate variability in the rat,
      hypothesizing that the quantitative information provided by this analysis
      reflects the interaction between sympathetic and parasympathetic regulatory
      activities. For this purpose, an electrocardiogram was recorded from conscious
      and unrestrained Wistar rats (Nippon, Shizuoka) (12-16 weeks old) by a telemetry
      system and analyzed by a power spectrum. Because it was thought that the
      electrocardiogram recorded by the telemetry system could provide more reliable
      data to assess autonomic nervous activity than the tethering system, the
      telemetry recording system was used. There were two major spectral components in
      the power spectrum at low frequency (LF) (0.6 Hz) and high frequency (HF)
      (approximately 1.4 Hz). On the basis of these data, the authors defined two
      frequency bands of interest: LF (0.04-1.0 Hz) and HF (1.0-3.0 Hz). The power of
      LF was higher than that of HF in the normal rat. Atropine (2 mg/kg
      intraperitoneally) significantly reduced both HF and LF power. Propranolol (4
      mg/kg intraperitoneally) also significantly reduced LF power; however, it had no
      significant effect on HF power. Thus, this study in the rat confirmed earlier
      observations in the conscious dog and human. Furthermore, the decrease in the
      parasympathetic mechanism produced by atropine was reflected by a slight increase
      in the LF/HF ratio. The LF/HF ratio appeared to follow the reductions of
      sympathetic activity produced by propranolol. From these results, the LF/HF ratio
      seemed to be a convenient index of parasympathetic and sympathetic interactions
      in the rat.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7815013
TI  - Exercise-induced complete heart block in a patient with chronic bifascicular
      block.
AB  - Heart block induced by exercise or associated with symptomatic, chronic
      bifascicular block can progress to high-grade atrioventricular (AV) block and
      sudden death. The authors describe a case of exercise-induced AV block in a
      patient with chronic bifascicular block. Thirty seconds of ventricular asystole
      were observed during exercise treadmill testing. Myocardial ischemia was ruled
      out, and the cause was determined to be distal AV nodal block. The
      pathophysiology, diagnosis, and treatment of distal AV nodal block are reviewed.
      The role of exercise treadmill testing and electrophysiologic studies in distal
      AV block are outlined in a diagnostic and therapeutic strategy.

PMID- 7815014
TI  - Torsade de pointes induced by terfenadine in a patient with long QT syndrome.
AB  - Torsade de pointes is a form of polymorphic ventricular tachycardia that is
      associated with prolongation of the QT interval. Although torsade de pointes is
      found in many clinical settings, it is mostly drug induced. Similar problems have
      been described with nonsedating H1-receptor antagonists, such as astemizole and
      terfenadine. Terfenadine is a widely used antihistamine. The authors report a
      case of torsade de pointes in a patient with a possible congenital sporadic form
      of QT interval prolongation who was receiving a therapeutic dose of terfenadine.

PMID- 7815015
TI  - Panoramic display of the orderly sequenced 12-lead ECG.
AB  - The standard 12-lead electrocardiogram (ECG) has been developed over many years.
      The ECG has had a long and successful history of providing diagnostic information
      in clinical medicine. Cardiac arrhythmias have been elucidated by deductive
      reasoning from continuous ECG recordings with confirmation from
      electrophysiologic studies. Recently, there has been renewed interest in the
      morphology of the QRS complex, ST-segment, and T wave, which raises the important
      question of considering whether the usual method of display provides maximal
      diagnostic capabilities. The conventional display provides a logical
      visualization of precordial lead recordings representing the horizontal plane,
      but does not provide a logical visualization of the limb lead recordings
      representing the frontal plane. Many clinical problems require the consideration
      of serial ECGs necessitating the comparison of separate pages. An alternate
      format presenting serial recordings on a single page would be advantageous. Some
      automated ECG analysis systems already include the capability for multiple
      display formats, but these have not yet been widely used in clinical practice.
      This point of view paper introduces a new display format for the standard 12-lead
      ECG that includes: (1) a presentation of an orderly sequence of leads to
      facilitate scanning through different points in space and (2) a presentation of
      recordings of 12-lead sequences to facilitate scanning through different points
      in time. This display format could either replace or supplement the conventional
      ECG format.

PMID- 7815016
TI  - Limitation of signal-averaged ECGs and measurement of late potentials in the
      presence of noise.

PMID- 7815017
TI  - Identification of sperm and non-sperm male cells in cervicovaginal smears using
      fluorescence in situ hybridization: applications in alleged sexual assault cases.
AB  - The identification of spermatozoa or constituents of seminal fluid is critical in
      the evaluation of alleged sexual assault victims. However, failure to identify
      sperm and/or elevated levels of acid phosphatase can occur for a variety of
      reasons. Molecular techniques, such as molecular cytogenetic analysis offers new
      approaches to improve on the identification of male cells in alleged sexual
      assault cases. Fluorescence in situ hybridization (FISH) with a Y chromosome
      specific DNA probe was applied to archival cervicovaginal smears from 41 alleged
      sexual assault cases to identify Y-bearing (male) cells. FISH identified Y
      bearing sperm and non-sperm cells in 78% of the cases previously confirmed to
      have sperm. FISH also identified Y-bearing non-sperm male cells in 39% of the
      cases in which cytology did not detect spermatozoa; in one of these instances, it
      also detected sperm. Cervicovaginal acid phosphatase levels, determined at the
      time of the cervicovaginal smears, were also compared with the presence or
      absence of Y-positive cells. Application of this technique can detect non
      spermatozoic male cells in routine cervicovaginal smears of sexual assault
      victims.

PMID- 7815018
TI  - Anomalous migration of PCR products using nondenaturing polyacrylamide gel
      electrophoresis: the amelogenin sex-typing system.
AB  - Sex-typing of biological samples can be accomplished using the polymerase chain
      reaction (PCR) to amplify DNA sequences that are specific for the Y-chromosome.
      One such system is based on PCR amplification of the X-chromosome amelogenin gene
      and the amelogenin-like sequences located near the centromere of the Y
      chromosome. The X and Y PCR products can be distinguished from each other on the
      basis of a 177 basepair (bp) insertion in the X relative to the Y. In this
      report, we demonstrate that the amelogenin PCR products migrate anomalously using
      non-denaturing polyacrylamide gel electrophoresis (ND-PAGE) as opposed to agarose
      gel electrophoresis or denaturing PAGE. These results may be relevant to the
      choice of electrophoretic system used to analyze highly polymorphic loci for
      individual identification.

PMID- 7815019
TI  - Assessing ethnicity from human mitochondrial DNA types determined by
      hybridization with sequence-specific oligonucleotides.
AB  - A logistic regression model was developed to predict ethnic group from
      mitochondrial DNA (mtDNA) types determined by hybridization with sequence
      specific oligonucleotide (SSO) probes of the two hypervariable segments of the
      mtDNA control region. The model was developed with, and tested against, a
      previously reported data set of 525 individuals from five ethnic groups (African
      American, Southeast Asian, Caucasian, Japanese, and Mexican) involving 23 probes
      at nine regions within the two hypervariable segments [1]. The model correctly
      predicted the ethnic group of 65.3% of the overall sample; however, the success
      rate varied substantially among ethnic groups, with the most success obtained
      with Caucasians (81% correctly classified). A discriminant analysis yielded
      similar results. An example is given of using the model to predict the ethnic
      group of an SSO-type from a forensic case. Such models provide alternatives to
      traditional skeletal-based methods of predicting ethnicity, especially in cases
      where skeletal material is absent or incomplete.

PMID- 7815020
TI  - Restriction fragment length polymorphism and polymerase chain reaction-HLA DQ
      alpha analysis of casework urine specimens.
AB  - DNA was isolated from casework urine samples previously submitted for
      toxicological analysis. The quality and quantity of DNA isolated was determined
      by spectrofluorometry and agarose yield gel electrophoresis. Hae III restricted
      samples were then resolved by analytical agarose gel electrophoresis, transferred
      to a membrane by Southern blotting and hybridized with a chemiluminescently
      labelled (D2S44) probe. The DNA fragment banding patterns were indistinguishable
      from the DNA banding patterns of blood specimens collected from the same donor.
      Only 5 of 20 samples yielded banding patterns and the banding intensity relative
      to background was low. Genomic DNA was also obtained from casework samples by
      Chelex extraction, amplified by polymerase chain reaction (PCR) and then
      genotyped for human leucocyte antigen (HLA) DQ alpha. Of 20 specimens, 13 (65%)
      were typed correctly producing identical results for urine and blood specimens
      obtained from the same donor. Aging studies of casework samples and normal
      samples (from a non-drug using population) were also conducted with PCR-HLA DQ
      alpha analysis. Results of these studies indicate that amplification by PCR was
      more likely to produce positive results. Based on these findings, we conclude
      that PCR-initiated analysis is more suitable than RFLP analysis for
      individualization of urine samples.

PMID- 7815021
TI  - Evaluating low-speed rear-end impact severity and resultant occupant stress
      parameters.
AB  - Automotive Systems Analysis, Inc. (ASA) and Lowell Hicks, Inc. (LHI) have
      developed a ground-up set of sensor instrumentation and recording method to
      document vehicle-artifact/occupant-stress parameters occurring from a continuing
      series of low-speed rear-end multi-vehicle impact tests (approximately 2 to 8
      MPH). This work has four goal areas: 1) calculate impacted vehicle (TARGET)
      barrier equivalent velocity (BEV) from isolator Artifacts; 2) correlate
      calculated BEV' to occupant stress; 3) calibrate injury potential of occupant
      stress impulse; 4) compare occupant stress with everyday volunteer activities.
      The test collision series now includes several different vehicle pairs with
      varying impact/escape speeds, weight ratios, and parallel parameters from a
      driver side manikin and passenger side volunteer. Observable physical vehicle
      isolator artifacts (piston stroke scrapes) were compared with computer-recorded
      linear sensor time traces, and these data were fitted to a 'calculated BEV'
      worksheet/algorithm. The worksheet/algorithm method shown here was found to be
      reasonably repeatable, per vehicle model and series tested. Next, manikin and
      volunteer occupant stress data, measured along with TARGET vehicle BEVs, were
      charted and compared with injury-threshold-impulse criteria referenced in the
      literature. Lastly, the occupant-stress impulses were compared with sample stress
      impulses for various volunteer physical activities, as a practical calibration of
      vehicle occupant stress.

PMID- 7815022
TI  - Estimation of dental age using HPLC-technique to determine the degree of aspartic
      acid racemization.
AB  - Age determinations of adult individuals are of great importance within the
      forensic sciences. Presently, age changes in the teeth provide good means for
      this. The best method up to now has been "Gustafson's method" with modifications.
      Over the last 10 years a new chemical method, based on the racemization of
      aspartic acid in enamel and dentine, has been developed. Enamel and dentine
      belong to the very few tissues that do not have metabolic turn-over after
      formation. Both reliability and validity have been shown to be high, and this
      method therefore seems to be the best choice for the future. However, most
      studies to date have been using expensive and special instruments (gas
      chromatographs or amino acid analyzers) for these determinations. This study was
      performed to explore if the same determinations can be carried out with ordinary
      HPLC technique. It was shown that there is a good correlation between the ratio
      of D- and L-forms of the aspartic acid and age of the tooth. The correlation
      coefficient was 0.97, which is close to those presented with the other
      techniques, where r has been 0.95 - 0.99. The prediction of an individual age can
      be made with a 95% confidence interval of about +/- 12 years.

PMID- 7815023
TI  - The descriptive epidemiology of unnatural deaths in Oregon's state institutions:
      a 25-year (1963-1987) study. IV. The reduction of unnatural death rates during
      1988-1992 in three facilities as a result of planned changes.
AB  - This paper documents the most recent five-year (1988-1992) analysis of unnatural
      deaths in Oregon's state mental and correctional institutions. The current
      findings are compared with those of the preceding five years (1983-1987) within
      the context of the long term trend in unnatural death rates for the previous 25
      years. The unnatural death rates for the institutional clients are also compared
      with those for the noninstitutionalized citizens of Marion County, Oregon. There
      are two major findings in these 1988-1992 data: (a) There have been highly
      significant reductions in unnatural death rates in Oregon State Hospital and in
      the Forensic Psychiatric Program, which the authors believe are largely due to
      the implementation of planned changes to reduce the previously very high suicide
      rates in these two facilities; and (b) There was a dramatic reduction (to zero)
      of unnatural deaths at the Fairview Training Center. The authors also believe
      that this was attainable mostly because of large-scale improvements made at that
      facility, by the Department of Human Resources and the Oregon Legislature, just
      before and during the present study time frame. Changes in these three facilities
      which led to the improvement in unnatural death rates of clients are discussed.

PMID- 7815024
TI  - The dangerousness of persons with the Othello syndrome.
AB  - The Othello syndrome, or delusional jealousy, often raises significant forensic
      issues, particularly dangerousness. Dangerous patients suffering from the Othello
      delusion may present with hostility ranging from verbal threats to homicidal
      acts. We present three cases of individuals suffering from Othello syndrome
      associated with significant hostility and organic mental factors. We analyze
      these cases along with Othello syndrome cases culled from the recent anglophonic
      literature, especially in terms of implications for domestic and public safety.

PMID- 7815025
TI  - A cognitive model of dangerous delusional misidentification syndromes.
AB  - The hallmark of the delusional misidentification syndromes is the presence of a
      misidentification delusion of the self or others. Delusional misidentification
      may present with an increased risk for dangerous behaviors. Individuals suffering
      from delusional misidentification syndromes may express hostility in ways ranging
      from serious verbal threats to homicidal acts. The causes of dangerous
      misidentification delusions remain for the most part undetermined. In this
      article, we report a series of six cases of individuals who harbored dangerous
      misidentification delusions. These individuals were studied phenomenologically
      and forensically. They were also studied biologically, including
      neuropsychological testing. A cognitive hypothesis aimed at explaining
      dangerousness and delusional misidentification is proposed. Implications of the
      hypothesis for further research are briefly outlined.

PMID- 7815026
TI  - Fatal carbon dioxide embolism complicating attempted laparoscopic cholecystectomy
      -case report and literature review.
AB  - Laparoscopic cholecystectomy has become the surgical procedure of choice for
      individuals with symptomatic gallbladder disease. The procedure has gained
      popularity among surgeons and patients because of inconspicuous abdominal
      incisions/scars, less postoperative pain, shorter hospitalization, and reduced
      medical costs. Bile duct, vascular, and gastrointestinal iatrogenic injuries are
      major complications. We describe the case of a 50-year-old woman who died of CO2
      embolism during elective laparoscopic cholecystectomy for symptomatic
      cholelithiasis. With the patient under general anesthesia, a 1.5 cm incision was
      made just below the umbilicus, and a pneumoperitoneum was created by CO2
      insufflation with a pneumoperitoneum (modified Veress) needle. Immediately, she
      experienced a cardiopulmonary arrest and could not be resuscitated. At autopsy,
      air bubbles were admixed with blood in the epicardial veins and leptomeningeal
      blood vessels. A triangular 0.1 cm perforation in the left common iliac vein had
      been created by the pneumoperitoneum needle. A pneumoperitoneum is required for
      laparoscopy and CO2 is the most commonly used gas. Carbon dioxide is highly
      soluble in blood and fairly innocuous to the peritoneum. Small amounts absorbed
      into the circulation cause slight increases in arterial and alveolar CO2 and in
      central venous pressure. When CO2 enters the venous circulation through
      iatrogenically opened vascular channels, catastrophic and potentially fatal
      hemodynamic and respiratory compromise may result.

PMID- 7815027
TI  - Acute aortic dissections and ruptured berry aneurysms associated with
      methamphetamine abuse.
AB  - Sudden, unexpected death can occur following rupture of an artery weakened by
      aneurysmal dilatation or by medial dissection. In both of these diseases the
      arterial abnormality is exacerbated by hypertension. This arterial weakness could
      also be aggravated by the use of drugs with a hypertensive effect. We report
      seven cases of sudden death in patients abusing methamphetamine--four cases of
      ruptured berry aneurysms and three cases of aortic dissection with cardiac
      tamponade. The autopsy findings are reviewed, and various mechanisms are
      considered by which methamphetamine may contribute to death in such cases.

PMID- 7815028
TI  - 125I radioimmunoassay for the dual detection of amphetamine and methamphetamine.
AB  - A radioimmunoassay that exhibits a nearly equivalent response to D-amphetamine
      and D-methamphetamine in urine over the assay range of 0 to 1000 ng/mL while
      displaying low cross-reactivity to L-amphetamine and L-methamphetamine (4.6% and
      2.4%, respectively) has been developed. In addition, methylenedioxy-amphetamine
      (MDA) and methylenedioxymethamphetamine (MDMA) were detectable in the assay with
      cross-reactivity levels of > 100% and 77% respectively. Little cross-reactivity
      was observed with the commonly encountered over-the-counter (OTC) drugs and this
      cross-reactivity was further reduced by the addition of sodium periodate into the
      reaction mixture to oxidize the beta-hydroxylamines. The double (second) antibody
      assay uses 125I-radiolabeled derivatives of both D-amphetamine and D
      methamphetamine as tracers in combination with two highly specific sheep antisera
      directed against D-amphetamine and D-methamphetamine. The assay exhibits a dose
      response of approximately 90,000 dpm from 0 to 1000 ng/mL of D-amphetamine or D
      methamphetamine with a minimum detectable dose for either drug of approximately
      25 ng/mL. With a cut-off level of 500 ng/mL, the assay gave a positive result for
      100% of the 111 clinical samples containing GC/MS confirmed (at or above the NIDA
      GC/MS cut-off values) levels of amphetamine and/or methamphetamine. Eighty-eight
      samples that screened negative in a clinical laboratory were all negative in the
      assay. Nineteen samples which were incorrectly identified as positive by other
      commercially available amphetamine assays were negative in this RIA.

PMID- 7815029
TI  - Hair analysis for buprenorphine and its dealkylated metabolite by RIA and
      confirmation by LC/ECD.
AB  - Hair samples were obtained from 14 subjects admitted 2 or 3 months previously to
      a detoxification center. All reported an history of intravenous heroin abuse.
      After decontamination by two dichloromethane washes, about 50 mg hair were
      pulverized in a ball mill and incubated at 56 degrees C overnight in 1 mL 0.1
      HCl. After neutralization, buprenorphine analyzed by RIA was in the range of 0.01
      to 0.47 ng/mg. To confirm buprenorphine, liquid chromatography was used. After
      neutralization, drugs were extracted with toluene at pH 8.5 during a 3-step
      extraction procedure. A portion of the reconstituted residue was injected into a
      Lichrosorb CN column, with a mobile phase of phosphate buffer (pH 4.0)
      acetonitrile-1-heptane sulfonic acid-butylamine (85:17:2:0.01, v/v). Detection
      was achieved by coulometry, and the potential of the electrodes was 0.15 and 0.50
      V, respectively. Linear calibration curves were obtained from 0.02 to 2.0 ng/mg
      with a correlation coefficient r > 0.99 for both drugs. The detection limit for
      the major metabolite was about 0.01 ng/mg and 0.02 ng/mg for buprenorphine, using
      a 50 mg hair sample. Recovery (at 0.2 ng/mg) was 54 and 62% for norbuprenorphine
      and buprenorphine, respectively. Drugs concentrations in hair were in the range
      0.02-0.59 and not detected--0.15 ng/mg for buprenorphine and norbuprenorphine,
      respectively. Results suggest that a dose-response relationship exists between
      the concentration of buprenorphine in hair and the administered dose.

PMID- 7815030
TI  - Improved gas chromatography/mass spectrometry analysis of barbiturates in urine
      using centrifuge-based solid-phase extraction, methylation, with d5-pentobarbital
      as internal standard.
AB  - Effective solid-phase extraction, derivatization, and GC/MS procedures are
      developed for the simultaneous determinations of butalbital, amobarbital,
      pentobarbital, and secobarbital, using a deuterated pentobarbital (d5
      pentobarbital) as the internal standard. Buffered (pH 7) urine samples were
      extracted with Bond Elute Certify II cartridge. Iodomethane/tetramethylammonium
      hydroxide in dimethylsulfoxide was used for methylation, while a HP 5970 MSD
      equipped with a 13 m J & W DB-5 column (5% phenyl polysiloxane phase) and the
      Thru-Put Target software package were used for GC/MS analysis and data
      processing. This protocol was found to be superior, in both chromatographic
      performance characteristics and quantitation results, over a liquid-liquid
      extraction procedure without derivatization using hexobarbital as the internal
      standard. Extraction recoveries observed from control samples containing four
      barbiturates range from 80% to 90%. Good one-point calibration data are obtained
      for all four barbiturates in the 50 to 3200 ng/mL range. Interestingly, the one
      point calibration data for pentobarbital are inferior to the other three
      barbiturates--due to interference from the internal standard (d5-pentobarbital).
      The calibration data of pentobarbital are best described by a hyperbolic curve
      regression model. Precision data (% CV) for GC/MS analysis, over-all procedure,
      and day-to-day performance are approximately 2.0%, 6.0%, and 8.0%, respectively.
      With the use of a 2 mL sample size, the attainable detection limit is
      approximately 20 ng/mL.

PMID- 7815031
TI  - Detection of cocaine, norcocaine, and cocaethylene in the meconium of premature
      neonates.
AB  - Our objective was to investigate the methodologic detection of cocaine abuse
      during pregnancy by determining the viability of meconium analysis for cocaine
      and its metabolites using chromatographic procedures as an alternative to urine
      testing using enzyme multiplied immunoassay technique. Our design was as follows:
      meconium and urine were taken from 106 very low birthweight premature babies.
      Meconium analysis for cocaine and its metabolites using extraction and
      chromatographic analysis was compared with the criterion standard immunoassay
      testing for urine. The work was carried out at The University of Chicago
      Hospital, Department of Pediatrics and the University of Illinois at Chicago,
      Department of Pharmacodynamics. Our patients were very low birthweight, premature
      babies (mean birthweight 1109 g; mean gestational age 29.1 weeks). Gender was
      evenly divided between male and female. The outcome measures were as follows: two
      active metabolites, norcocaine and cocaethylene, were detected in the meconium,
      but not in the urine, of some of the neonates. Determination of cocaine exposure
      in the newborn influenced assignment of babies in research studies as well as
      psychosocial evaluation and subsequent treatment of the neonate. Our results
      were: of the 106 meconium samples analyzed, 21 (19.8%) were positive for cocaine
      (n = 19, 0.24-0.78 mg/kg), norcocaine (n = 7, 0.10-0.56 mg/kg), cocaethylene (n =
      1, 0.12 mg/kg) or combinations thereof. Benzoylecgonine was not detected in any
      of the samples. Of the urine samples analyzed by immunoassay, only 8 (7.5%) were
      positive for cocaine metabolites. We conclude that meconium is a better sample
      than urine for determining cocaine exposure in utero.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7815032
TI  - Evaluation of canines for accelerant detection at fire scenes.
AB  - In recent years, canines have been successfully used in fire investigations to
      detect accelerant residues. We set out to determine the lower limits at which
      canines could reliably detect potential accelerants. Measured amounts ranging
      from 10 to as little as 0.01 microL of gasoline, kerosene, and isopars were
      applied to preselected spots along a continuous sample path (25 to 40 feet long)
      made out of burned and unburned wood or nylon carpeting strips at the testing
      site. Two canines were led past this sample path at least three times and
      positive alerts and negative responses were recorded. Both dogs were generally
      able to alert on spots containing 0.01 microL or more of all three accelerants,
      at or beyond the purge and trap recovery and gas chromatographic detection method
      employed. The canines did alert occasionally on background, especially that
      containing traces of styrene residues, either purposely added in specific amounts
      or formed upon partial pyrolysis of carpeting material. The dogs alerted on sites
      containing 0.1 to 1.0 microL of freshly applied gasoline or kerosene placed at
      actual heavily damaged fire scenes, but were less successful on samples
      containing smaller amounts.

PMID- 7815033
TI  - Detection and determination of pseudococaine in coca leaves and illicit cocaine
      samples.
AB  - Methodology is presented for the isolation, identification and determination of
      pseudococaine in coca leaves and illicit cocaine. Coca leaves, crude cocaine base
      (coca paste), refined cocaine base and refined cocaine hydrochloride, all derived
      from the same geographic location in Bolivia, were examined. Pseudococaine and
      other coca alkaloids were isolated from leaf samples using toluene extraction
      followed by acid/Celite trap and ion-pair column chromatography, and from crude
      and refined cocaine samples by acid/Celite column ion-pairing chromatography.
      Mass spectral analysis of coca leaf isolates confirmed the presence of
      pseudococaine. Pseudococaine was quantified by capillary gas chromatography with
      flame ionization detection at levels of 0.0001-0.035% (relative to cocaine) in
      refined illicit cocaine and coca leaves.

PMID- 7815034
TI  - Recapturing a five-month-old bite mark by means of reflective ultraviolet
      photography.
AB  - After a brutal rape, which the victim survived, a bite mark was photographed and
      other evidence was collected. It was not until several months later when the bite
      mark became a critical piece of evidence, that the problem with its collection
      became apparent to the prosecutor. The photograph of the bite mark taken by law
      enforcement officials at the time of the crime did not include a reference scale.
      Therefore the bite mark was of little evidentiary value. The authors subsequently
      examined the victim (five months later) and "recaptured" the bite mark pattern
      with a proper reference scale by means of reflective ultraviolet photography.

PMID- 7815035
TI  - Suicidal cyanide ingestion as detailed in Final Exit.
AB  - Final Exit is an "informational aid" advocating the practice of active euthanasia
      and describing the proper method for the foolproof commission of suicide.
      Although it has been directed toward assisting the terminally ill patient who
      desires to terminate suffering, it has been suggested that the widespread
      availability of this book may result in its abuse. Specifically, there is growing
      concern that "do-it-yourself suicide manuals" could bring about the fruition of
      suicidal ideations that are relatively common among mentally ill patients and
      impressionable adolescents. Described is the suicidal ingestion of cyanide by a
      physically healthy 30-year-old man. His diary, found next to the body, contains a
      recipe for suicide copied verbatim from Derek Humphry's Final Exit. Although the
      decedent's history, the scene investigation, and the external examination
      strongly suggest an underlying psychiatric disorder, postmortem examination
      disclosed minimal underlying physical disease. This case graphically illustrates
      the abuse potential of this literary genre. To our knowledge, this is the first
      case of its kind to appear in the literature. We recommend that forensic
      pathologists and medical investigators familiarize themselves with the methods of
      suicide described in Final Exit.

PMID- 7815036
TI  - A fatality due to flurazepam.
AB  - A fatality attributed to suicidal ingestion of up to 2.2 grams of flurazepam is
      described. The deceased was a 52-year old female with a history of depression and
      suicidal attempts. No significant pathology was found at autopsy. Full
      toxicological analyses detected only flurazepam and metabolites in her tissues.
      The concentrations of flurazepam in femoral blood, liver, bile, vitreous humor
      and urine were 5.5 mg/L, 130 mg/kg, 33 mg/L, 1.3 mg/L and 3.3 mg/L, respectively.
      Analysis of gastric contents showed 600 mg of flurazepam. Desalkylflurazepam was
      also detected in blood, liver, bile and vitreous, but at much lower
      concentrations than the parent compound.

PMID- 7815037
TI  - Medical toxicology.

PMID- 7815038
TI  - Florida Poison Information Network. Saving lives and money.
AB  - A highly sophisticated network of poison information centers exists in Florida,
      one each in the northern, central and southern regions of the state. These 24
      hour-a-day centers are staffed by nurses and pharmacists who provide assessment,
      triage and management advice about a wide range of exposures. Toxicologists are
      available when in-depth consultation is needed. As most cases can be safely
      managed at home, costly visits to the emergency room are averted, resulting in
      significant overall health-care savings. These centers also provide educational
      programs for the public and health professionals and compile epidemiologic
      statistics.

PMID- 7815039
TI  - Common plant ingestions.
AB  - Of the enormous number of calls regarding toxic and nontoxic plant ingestions
      received by the Florida Poison Information and Toxicology Resource Center each
      year, the majority are about accidental ingestions in the pediatric population.
      These tend to involve household plants ranging from nontoxic to those with life
      threatening cardiotoxicity. Several recent cases of ingestions with the intent of
      producing hallucinogenic effects have been presented to the Poison Center. Other
      misadventures have resulted from the similar appearance of toxic and nontoxic
      plants. The three poison centers in Florida have access to toxicologic
      consultation to help the clinician assess the severity of a plant poisoning and
      to guide in treatment decisions.

PMID- 7815040
TI  - Gastrointestinal decontamination for acute poisoning by ingestion. Prevention of
      absorption of toxic compounds.
AB  - Gastrointestinal decontamination therapy in the patient with accidental or
      intentional ingestion of toxic substances has been standard therapy for several
      decades, although based on theory of presumed action and benefit. As scientific
      knowledge accumulates in this area of clinical toxicology, old assumptions are
      being challenged by scientific evidence relating to gastric emptying, efficacy of
      activated charcoal, and usefulness of whole-bowel irrigation with polyethylene
      glycol electrolyte lavage solutions. An overview is presented of the scientific
      data now available. Although realizing the still unresolved controversies, a
      logical plan is described for gastrointestinal decontamination following acute
      overdose.

PMID- 7815041
TI  - Emergency care of insecticide poisonings.
AB  - Insecticide poisoning is an increasing event which requires a thorough knowledge
      base for diagnosis and management. Awareness of the importance of decontamination
      is fundamental not only in the prehospital care phase but also in the emergency
      department. A thorough knowledge of the essentials of emergency and critical care
      is indispensable for the management and support of ventilatory and circulatory
      functions. Specific antidotal therapy utilizing atropine and pralidoxime is
      usually necessary in the immediate care of acute cases. In addition, use of
      pralidoxime after acute exposure may contribute to a beneficial outcome.
      Appropriate laboratory determinations in the acute phase are necessary parameters
      for successful outcomes. The use of cholinesterase determinations for diagnostic
      and prognostic purposes is discussed.

PMID- 7815042
TI  - Prescription for disaster.

PMID- 7815043
TI  - Alzheimer's disease. Molecular genetics.

PMID- 7815044
TI  - Preventing falls and fractures.
AB  - One of four persons over age 65 in the community falls; those over age 75 in
      institutions fall more frequently. Falls, a complex phenomena suggesting present
      disease and predicting future disability, are caused by interactions between the
      environment and dynamic balance which is determined by the quality of sensory
      input, central processing, and motor responses. Clinical factors which predispose
      to falling often produce observable disturbances in gait and balance, making
      observation critical in assessment. Acute illness and drug therapy produce
      particularly preventable falls. Therapeutic exercise and environmental
      modification for safety are the clinical interventions most likely to
      successfully prevent fall-related injury.

PMID- 7815045
TI  - The lull before the storm. The GLN can help.

PMID- 7815046
TI  - Prochoice is good for medicine.

PMID- 7815047
TI  - Extraversion, neuroticism, and face-name learning.
AB  - Previous research has attempted to relate personality traits to paired-associate
      learning. We tested name recall as a function of extraversion and neuroticism (as
      assessed by the Eysenck Personality Inventory) and task difficulty. Face
      photographs were paired with one of three levels of information: names only (an
      easy task); names and occupations; or names, occupations, and interests (a
      difficult task). On the easy and difficult tasks, extraverted subjects recalled
      more names than did subjects scoring at the median or below on that trait.
      Contrary to expectations, subjects scoring high on neuroticism recalled more
      names than did subjects scoring low on that trait. Neither trait was
      significantly related to recall on the moderately difficult task. There was no
      interaction between traits for name recall, but there was for interests: Neurotic
      introverts were significantly impaired at recalling interests, whereas the other
      subjects recalled interests better than names. These findings thus differ from
      those of paired-associate learning tasks using words and nonsense syllables.

PMID- 7815048
TI  - Positive and negative mood effects in children: the mediating influence of task
      characteristics.
AB  - This study was designed to investigate positive and negative mood effects in
      children of different ages (younger children: n = 90, mean age 7 years 3 months;
      older children: n = 92, mean age 11 years 3 months). Children were asked to
      evaluate schematic drawings and photographs of ambiguous facial expressions after
      a happy, a sad, or a neutral mood induction had taken place by means of a mental
      imagery procedure. In both age groups, mood effects proved to be dependent on the
      nature of the judgment task. Positive and negative mood effects were found on
      children's judgments of schematic drawings, whereas the evaluation of photographs
      resulted in a positive bias only. The results are discussed within the scope of a
      multiprocess view of the relation between affect and cognition (Forgas, 1991,
      1992) and a recent model on mood-sensitive task characteristics (Fiedler, 1991).

PMID- 7815049
TI  - Rule-governed performance and sensitivity to contingencies: what's new?
AB  - Human operant performance was treated as an instance of instrumental problem
      solving behavior. All subjects completed the same series of six water jug
      problems, the first three requiring an elaborate formula, and the last three
      allowing simpler solutions. Experimental subjects were informed that all problems
      could be solved using the same (elaborate) formula. Experimental subjects solved
      quickly but failed to use more efficient solutions. Instructions led to more
      reported compliance with perceived "demand characteristics," continued use of the
      more elaborate solution for the sake of speed and convenience, and the
      expectation that fewer problems allowed alternative solutions. It was suggested
      that sensitivity to contingencies and the Einstellung Effect (as explicated by
      Luchins 50 years ago) appear to be homologous phenomena and may be expected to
      share common behavioral processes.

PMID- 7815050
TI  - Cohort effects in the lateral preference of Japanese people.
AB  - Handedness data of the Japanese were collected twice with an interval of 20
      years, using an identical handedness inventory. In the second cohort, non-right
      handers among male and female students numbered 11.5% and 5.9%, respectively. The
      results showed that the incidence of non-right-handedness among Japanese females
      has increased from 20 years ago.

PMID- 7815051
TI  - Technology and older adults: factors affecting the adoption of automatic teller
      machines.
AB  - Although technology can benefit service providers, caregivers, and the elderly,
      its application in an aging society can bring special challenges. This study
      looked at older adults' adoption of one technology that is highly prevalent in
      modern society--the automatic teller machine (ATM). The findings indicated that
      users and nonusers differed in mechanical reasoning skills and in attitudes
      toward ATM technology. Older adults with higher mechanical reasoning skills were
      more likely to be ATM users. Nonusers had more negative attitudes toward ATMs,
      and, among nonusers, those who had tried an ATM had more positive attitudes than
      those who had never tried one. The findings of this study are discussed in terms
      of factors that may affect the adoption of other technologies by older adults.
      Suggestions for increasing the acceptance of technologies by the elderly are also
      addressed.

PMID- 7815052
TI  - Radial aftereffect of induced motion (IMAE): perception during monocular viewing
      with minimal background pattern.

PMID- 7815053
TI  - Specific pathway selection by the early projections of individual peripheral
      sensory neurons in the embryonic medicinal leech.
AB  - In leech, the central annulus of each midbody segment possesses seven pairs of
      sensilla, which are mixed clusters of primary peripheral sensory neurons that
      extend their axons into the CNS where they segregate into distinct fascicles.
      Pathway selection by individual afferent growth cones of sensillar neurons was
      examined by double labeling using intracellular dye-filling with antibody
      labeling in early Hirudo medicinalis embryos. The monoclonal antibody Lan3-2 was
      used because sensillar neuronal tracts are specifically labeled by this antibody.
      Examining 68 individually filled neurons we found that sensillar neuron growth
      cones bifurcate within the CNS, that they project long filopodia capable of
      sampling the local environment, and that all of them appeared to choose a single
      particular CNS fascicle without apparent retraction or realignment of growth
      cones. Furthermore, each side of the bifurcating afferent growth cones always
      chose the same fascicle, implying a specific choice of a distinct labeled
      pathway. By dye-filling individual central neurons (P-cells), we show that there
      are centrally projecting axons present at the time sensillar afferents enter the
      ganglionic primordia and select a particular fascicle, and we confirm that at
      least the dorsal peripheral nerve is likely to be pioneered by central neurons,
      not by the peripheral afferents. In the sensillum studied here, we found examples
      of sensory neurons extending axons into one of all the available fascicles. Thus,
      an individual embryonic sensillum possesses a heterogeneous population of
      afferents with respect to the central fascicle chosen. This is consistent with
      the idea that segregation into distinct axon fascicles may be based upon
      functional differences between individual afferent neurons. Our findings argue
      strongly in favor of specific pathway selection by afferents in this system and
      are consistent with previous suggestions that there exists a hierarchy of cues,
      including surface glycoconjugates that mediate navigation of the sensillar growth
      cones and the fasciculation of their axons.

PMID- 7815054
TI  - Identification of CDK- and cyclin-like proteins in the eye of Bulla gouldiana.
AB  - The ocular circadian rhythm in the eye of Bulla gouldiana is generated by a
      rhythm in membrane potential of retinal neurons that is driven by alterations in
      potassium conductance. Since potassium conductance may be modulated by the
      phosphorylation of potassium channels, the circadian rhythm may reflect rhythmic
      changes in protein kinase activity. Furthermore, the circadian rhythm recorded
      from the Bulla eye can be phase shifted by agents that affect protein synthesis
      and protein phosphorylation on tyrosine residues. Interestingly, the eukaryotic
      cell division cycle is generated by similar processes. Rhythmic cell division is
      regulated by periodic synthesis and degradation of a protein, cyclin, and
      periodic tyrosine phosphorylation of a cyclin-dependent kinase (cdk), p34cdc2.
      The interaction between these two proteins results in rhythmic kinase activity of
      p34cdc2. Both cyclin and p34cdc2 are part of two diverse gene families, some of
      whose members have been localized to post-mitotic cell types with no function yet
      determined. In the current work, we identify proteins similar to the cdks and
      cyclin in the eye of Bulla. Neither of these ocular proteins are found in mitotic
      cells in Bulla, and the cdk-like protein (p40) is specific to the eye.
      Furthermore, the concentration of the cyclin-like protein (p66) is affected by
      treatments that phase shift the circadian rhythm. The identification of cdk and
      cyclin-like proteins in the Bulla eye is consistent with the hypothesis that the
      biochemical mechanism responsible for generating the ocular circadian rhythm in
      Bulla is related to the biochemical mechanism that regulates the eukaryotic cell
      division cycle.

PMID- 7815055
TI  - Neuronal differentiation of PC12 cells as a result of prevention of cell death by
      bcl-2.
AB  - Rat pheochromocytoma PC12 cells die when cultured in serum-free medium.
      Neurotrophic factors can rescue PC12 cells from cell death, and induce neuronal
      differentiation. To further investigate the relationship among cell death,
      survival, and differentiation, the bcl-2 cDNA, which is known to prevent
      apoptosis in various types of cells, was transfected into PC12 cells. Six
      monoclonal bcl-2-transfected cell lines were isolated and confirmed to express
      mRNA and protein product of bcl-2. The wild-type and bcl-2-transfected PC12 cells
      were kept to adhere to collagen-coated dishes at the initiation of serum-free
      experiments to avoid cellular damage due to detachment of the cells by
      trituration. Even under the conditions, the control PC12 cells mostly died within
      24 h, when cultured in serum-free medium, whereas those expressing Bcl-2 survived
      even for 7 days in serum-free medium. Moreover, outgrowth of long processes in
      the bcl-2-transfected cells was only observed under the condition to keep the
      cells attached to the dishes in serum-free medium without any additive
      neurotrophic or growth factors. Neurofilament medium protein, which is a neuron
      specific cytoskeletal component, was also expressed in the differentiated cells,
      suggesting that the long processes in bcl-2-transfected PC12 cells are neurites.
      However, neuronal differentiation of PC12 cells expressing Bcl-2 was not observed
      when cultured in serum-containing medium. Accordingly, survival of PC12 cells
      expressing Bcl-2 under the condition which cells usually die may be accompanied
      with neuronal differentiation.

PMID- 7815056
TI  - Maturation of neurites in mixed cultures of spinal cord neurons and muscle cells
      from Xenopus laevis embryos followed with antibodies to neurofilament proteins.
AB  - Dissociated cell cultures of Xenopus laevis embryonic spinal cord have proved
      useful for studying the differentiation of neuronal ionic channels and membrane
      properties and for examining the dynamics of microtubules in developing neurons.
      To examine their usefulness for studying neurofilaments in developing neurites,
      we prepared similar cultures from stage 22 embryos. Between 3 and 55 h after
      plating, these cultures were fixed and immunostained with antibodies directed
      against various epitopes of neurofilament proteins from X. laevis. These
      antibodies were specific for nonphosphorylated epitopes of the two low molecular
      weight Xenopus neurofilament proteins (Xenopus NF-L and the Xenopus neuronal
      intermediate filament protein, XNIF), both phosphorylated and nonphosphorylated
      epitopes of the Xenopus middle molecular weight neurofilament protein (NF-M), and
      a nonphosphorylated epitope of the Xenopus high molecular weight neurofilament
      protein (NF-H). The emergence of these neurofilament proteins in culture was
      compared to the time course previously reported for them in Xenopus spinal cord
      neurons in situ. To facilitate the comparison of times in culture to
      developmental stages, the age of cultured neurons was converted to an equivalent
      Nieuwkoop and Faber normal stage using data presented here on the effect of
      changing temperature on developmental rates of X. laevis. With the exception of
      the nonphosphorylated epitope of NF-H, which is indicative of the most mature
      axons found in situ, the emergence of the other neurofilament protein antibody
      epitopes closely paralleled that previously reported for these antibodies in
      situ. Thus, with respect to XNIF, NF-M, and NF-L, the neurites of cultured
      neurons were typical of young, embryonic Xenopus laevis spinal cord axons. This
      system should prove useful for studying both the function of these neurofilament
      proteins during the early stages of axonal development and the dynamics of their
      transport.

PMID- 7815057
TI  - Influence of factors released from sciatic nerve on adult dorsal root ganglion
      neurons.
AB  - Previous experiments have shown that medium conditioned (CM) by denervated
      peripheral nerve contains a process outgrowth promoting factor(s) for cultured
      adult frog dorsal root ganglion (DRG) neurons. The present experiments further
      characterize the influences of these factors on DRG neurons. The growth factors
      increases average process length by threefold, restricts the number of processes
      extended from four to two while simultaneously altering the morphology of those
      processes. Neurons with preexisting processes respond to the factors by
      significantly increasing the length of 35% of these processes. Only the newly
      elongated portions of preexisting processes have a morphology typical of factor
      induced processes, while the previously extended portions retain their original
      morphology. The number of processes of these neurons remains unchanged. Although
      composed of two populations according to size, neurons in both populations are
      similarly influenced, suggesting that the factors influence neurons of all
      sensory modalities. To look at other possible influences of the nerve-released
      factors, a novel simple culture system has been developed in which concentration
      gradients of these factors can be established and maintained. The front of the
      outgrowth-promoting influence in these cultures could be followed over time (up
      to 9 days) as it affected the process length and morphology of neurons at
      increasing distances (up to 8 mm) from the source of the factors. The trophic
      factors may play important roles during regeneration in vivo by influencing the
      cytoskeletal organization in the cell body and growth cones to bring about a
      stabilization and consolidation of growth cone membrane of only a limited number
      of processes resulting in increasing the rate of process elongation. The factors
      may also serve to direct process outgrowth, which can be examined using the new
      culture system.

PMID- 7815058
TI  - Neurotrophic influence of denervated sciatic nerve on adult dorsal root ganglion
      neurons.
AB  - Isolated adult frog dorsal root ganglion neurons survive in vitro in a defined
      medium for more than 4 weeks and extend processes. When co-cultured with a 1-mm
      piece of peripheral nerve the average total process length per neuron was 10
      times longer than that of control neurons by 8 days, and the processes had a
      significantly different morphology from that of control neurons. This influence
      on process length increased with increasing time of nerve denervation prior to co
      culturing. These results suggest the release of a neurotrophic factor/s from the
      cells of the peripheral nerve. The neurotrophic influence was completely blocked
      by antibodies against mouse nerve growth factor (NGF). Although NGF increased the
      average process length by twofold over control neurons, its influence nerve
      reached that of the nerve-released factor, and the NGF-induced processes had a
      distinctly different morphology. The frog nerve-released factor promoted process
      outgrowth from E11 chick sympathetic ganglia, although the process number,
      length, and their fasciculation differed greatly from those induced by NGF. These
      results suggest that the nerve-released factor/s are immunologically and
      functionally related to NGF but have not established whether a single factor or
      an aggregate of several secreted molecules are responsible. This article presents
      a new preparation in which the varied influences of different neurotrophic
      factors can be studied in great detail on large populations of isolated adult
      vertebrate neurons and sets the stage for the characterization and isolation of
      the frog peripheral nerve neurotrophic factor, as well as examining the influence
      of this factor on neuronal morphology and its ability to direct process
      outgrowth.

PMID- 7815059
TI  - Neuronal responses to purinoceptor agonists in the leech central nervous system.
AB  - Extracellular nucleotides like ATP and its derivatives are possible chemical
      messengers in vertebrate nervous systems. In invertebrate nervous system,
      however, little is known about their role in neurotransmission. We have studied
      the response of identified neurones of the leech Hirudo medicinalis to the
      purinoceptor agonist ATP, ADP, AMP, and adenosine using conventional
      intracellular microelectrodes and whole-cell patch-clamp recording. Bath
      application of the agonists depolarized the different neurons, but not the
      neuropil glial cells. The most effective responses (up to 10 mV) were observed
      with ATP (100 microM) or ADP (100 microM) in the noxious and touch cells. In most
      neurons the nonhydrolyzable ATP derivative ATP-gamma-S (5 microM) induced larger
      depolarizations than 100 microM ATP, indicating that most of the potency of ATP
      is lost presumably due to its degradation by ectonucleotidases. In medial noxious
      cells, ATP (100 microM) induced an inward current of 1.7 +/- 1.1 nA at a holding
      potential of -60 mV. The ATP-induced current-voltage relationship showed an
      inward rectification and a reversal potential close to 0 mV. In a Na+-free
      extracellular solution, the ATP-induced inward current decreased and in a Na+-
      and Ca(2+)-free saline only a small residual current persisted. The possible P2
      purinoceptor antagonist suramin did not antagonize the ATP-induced current, but
      itself evoked an inward current and a conductance increase. We conclude that ATP
      activates nonselective cation channels in medial noxious cells of the leech with
      the order of potency of purinoceptor agonists ATP > or = ADP > AMP. The results
      suggest that these cells express purinoceptors of the P2 type.

PMID- 7815061
TI  - Kinase requirement for retinal growth cone motility.
AB  - Since cytoplasmic Ca2+ levels are reported to regulate neurite elongation, we
      tested whether calcium-activated kinases might be necessary for growth cone
      motility and neurite elongation in explant cultures of goldfish retina. Kinase
      inhibitors and activators were locally applied by micropipette to retinal growth
      cones and the responses were observed via phase-contrast videomicroscopy. In some
      cases, growth rates were also quantified over several hours after general
      application in the medium. The selective inhibitors of protein kinase C,
      calphostin C (0.1-1 microM) and chelerythrin (up to 50 microM), caused no obvious
      changes in growth cones or neurite elongation, and activators of PKC (phorbols,
      arachidonic acid, and diacylglycerol) also were generally without effects,
      although phorbols slowed the growth rate. Inhibitors of protein kinase A and
      tyrosine kinases also produced no obvious effects. The calmodulin antagonists,
      calmidazolium (0.1 microM), trifluoperazine (100 microM), and CGS9343B (50
      microM), however, caused a reversible growth cone arrest with loss of filopodia
      and lamellipodia. The growth cone became a club-shaped swelling which sometimes
      moved a short distance back the shaft, leaving evacuated filaments at points of
      strong filopodial attachments. A similar reversible growth cone arrest occurred
      with the general kinase inhibitors: H7 at 200 but not at 100 microM, and
      staurosporine at 100 but not 10 nM, suggesting possible involvement of a
      calmodulin-dependent kinase (camK) rather than PKC. The selective inhibitor of
      camKII, KN-62 (tested up to 50 microM), produced no effects, but the specific
      myosin light-chain kinase (MLCK) inhibitors ML-7 (3-5 microM) and ML-9 (5-10
      microM) reversibly reproduced the effect, suggesting that MLCK rather than camKII
      is necessary for growth cone motility. The MLCK inhibitors' effects both on
      growth cone morphology and on F-actin filaments (rhodamine-phalloidin staining)
      were similar to those caused by cytochalasin D (5 microM), and are discussed in
      light of findings that inhibiting MLCK disrupts actin filaments in astrocytes and
      fibroblasts.

PMID- 7815060
TI  - Expression of winged helix genes, BF-1 and BF-2, define adjacent domains within
      the developing forebrain and retina.
AB  - One of the earliest events in the development of the central nervous system is
      the establishment of positional identity along the anteroposterior (A-P) axis of
      the neuroepithelium. In recent years, regulatory genes with regionally restricted
      expression in the neuroepithelium have been identified which are believed to
      specify its developmental fate. We have previously described Brain Factor-1 (BF
      1), a winged helix (WH) transcription factor expressed in the telencephalic
      neuroepithelium (Tao and Lai, 1992) Neuron 8:957-966. Here we report the cloning
      of the mouse cDNA for a novel WH protein, BF-2. We show that BF-2 is a sequence
      specific DNA binding protein with a binding specificity distinct from BF-1. Its
      expression in the CNS during embryogenesis is restricted to the rostral
      diencephalic neuroepithelium. The caudal boundary of BF-2 expression is at the
      zona limitans intrathalamica. Rostrally, the BF-2 expression domain is adjacent
      to that of BF-1. The expression domains of these two factors define a boundary
      within the developing forebrain neuroepithelium. The BF-1/BF-2 boundary also
      extends laterally to divide the optic stalk and the retina into nasal (anterior)
      and temporal (posterior) domains. These observations suggest that in addition to
      playing a role in the subdivision of the forebrain, these two WH factors may also
      function to establish positional information in the retinal neuroepithelium.

PMID- 7815062
TI  - Sexual differentiation in the CNS of the moth, Manduca sexta. I. Sex and segment
      specificity in production, differentiation, and survival of the imaginal midline
      neurons.
AB  - We analyzed the development of several sets of postembryonic sex-specific
      motoneurons in Manduca sexta which belong to a group of homologous lineages of
      neurons called the imaginal midline neurons (IMNs). Adult female oviduct
      motoneurons and male sperm duct motoneurons are IMNs that show similar anatomical
      features and differentiate during metamorphosis, despite appearing in different
      segments: A7 for oviduct neurons, A9 for sperm duct neurons. These cells are born
      at the same time and, initially, similar sets are found in A7 and A9 ganglia of
      larvae of both sexes. The dimorphic adult pattern is generated by sex-specific
      production and cell death. A7 IMNs differentiate in both sexes through early
      pupal stages, whereupon they disappear in the male and become the oviduct
      motoneurons in the female. A9 IMNs are overproduced in the male, and subsequent
      cell death reduces male cell number and eliminates the small complement of female
      cells; the surviving male cells develop into the sperm duct motoneurons. Similar
      IMN arrays are generated in nongenital ganglia, but show non-sex-specific fates.
      This suggests that both the sex of these cells and their segment of residence
      play major roles in their subsequent differentiation.

PMID- 7815063
TI  - Sexual differentiation in the CNS of the moth, Manduca sexta. II. Target
      dependence for the survival of the imaginal midline neurons.
AB  - While the majority of neurons in the adult nervous system of the moth Manduca
      sexta are produced postembryonically, little is known about how these cells
      interact with their targets during development. Few of these cells are motor
      neurons; most of Manduca's adult motor neurons are respecified larval motor
      neurons that developed embryonically. A few motor neurons do develop
      postembryonically, including a large class of mixed neurosecretory and motor
      neurons called the imaginal midline neurons (IMNs). A subset of these cells show
      an unusual pattern of sex-specific development and survival (Thorn and Truman,
      1994, J. Neurobiol. in press), which led us to suspect that factors extrinsic to
      the cells were controlling their fates. We analyzed one such potential factor by
      altering the contacts between a subset of these developing IMNs and their adult
      specific target, the male sperm duct. When we transected the nerve that
      innervated the sperm duct in the pupa, we observed a loss of many sperm duct
      IMNs. In contrast, a transection of the same nerve in larvae showed no neuron
      loss. Immunocytochemistry showed that the pupal nerve transections were
      accompanied by a loss of axon endings on the sperm duct, while the larval nerve
      transections showed no such loss. Using local hormone application to slow the
      development of the sperm duct while leaving the nerve intact still resulted in a
      loss of IMNs. These results suggest that these IMNs need contact with a robust
      developing target in the pupa to survive metamorphosis.

PMID- 7815064
TI  - Neural organization of the ventilatory activity in the frog, Rana catesbeiana. I.
AB  - In order to elucidate the neural basis for lung ventilation in the frog, we have
      investigated the efferent neural activity to oropharyngeal muscles in the
      decerebrate, paralyzed, unanesthetized bullfrog, Rana catesbeiana. Efferent motor
      output was recorded from the mandibular branch of the trigeminal (Vmd), the
      laryngeal branch of the vagus (Xl), and the main and sternohyoid branches of the
      hypoglossal nerve (Hm and Hsh, respectively). Two types of rhythmic bursting
      outputs were observed: (1) a high-frequency, low-amplitude, reciprocal
      oscillation between Vmd, a buccal levator nerve, and Hsh, a buccal depressor
      nerve; and (2) a low-frequency, high-amplitude, synchronous bursting of Vmd, Hm,
      Hsh, and Xl. The first type is inferred to represent fictive oropharyngeal
      ventilation. The second type of burst was divided into four intervals: (a)
      augmenting activity of Hsh; (b) activation of Xl with continued activation of
      Hsh; (c) activation of Vmd and Hm (a buccal levator nerve), continued activation
      of Xl, and termination of Hsh activity; and (d) warning activity in Vmd and Hm
      associated with a prominent second wave in Xl. This coordinated activity is
      inferred to represent fictive pulmonary ventilation because the neurograms in
      these four intervals correspond closely to EMGs and neurograms recorded in the
      intact frog during the four phases of pulmonary ventilation, namely, buccal
      depression, pulmonary expiration, pulmonary inspiration, and glottal closure.
      Hypercapnia, vagotomy, and cutaneous pinching enhanced the high-amplitude, low
      frequency rhythm, but not the low-amplitude, high-frequency oscillation. Lung
      inflation generally inhibited the former and not the latter, but in some cases
      lung inflation stimulated pulmonary ventilation. We conclude that oropharyngeal
      and pulmonary ventilation of the frog are produced by one or, possibly, two
      intrinsically active generators.

PMID- 7815065
TI  - Neural organization of the ventilatory activity in the frog, Rana catesbeiana.
      II.
AB  - The paralyzed, decerebrate frog, Rana catesbeiana, displays "fictive"
      oropharyngeal and pulmonary ventilations. In order to evaluate the neuronal
      correlates of these two centrally programmed ventilatory bursting patterns, we
      have performed intra- and extracellular recordings of bulbar respiratory neurons
      in this fictively breathing preparation. A total of 123 respiratory neurons were
      recorded from the caudal medulla. Of 51 antidromically activated neurons, 20 were
      vagal motoneurons and 31 were hypoglossal motoneurons. Respiratory neurons that
      depolarized during the lung (L) or non-lung (N) ventilatory phases were
      classified as L or N neurons, respectively. Phase spanning neurons (S) were
      active during both L and N phases. Some neurons showed oscillations of membrane
      potential synchronous with oropharyngeal ventilation. Those active during the
      buccal elevation phase were exclusively L neurons, whereas those having buccal
      depressor activity were exclusively N neurons. Synaptic drive potentials were
      observed in all neurons recorded intracellularly. In some neurons,
      hyperpolarization was caused by inhibitory postsynaptic potentials, as
      demonstrated by reversal of membrane potential trajectory after intracellular
      chloride iontophoresis. Some individual motoneurons and interneurons exhibited
      both pulmonary and buccal ventilatory activity, indicating that both pattern
      generators project to a common motor control system.

PMID- 7815066
TI  - The TRH neuronal phenotype forms embryonic cell clusters that go on to establish
      a regionalized cell fate in forebrain.
AB  - How neurons diversify in developing brain to produce discrete cell fates in their
      appropriate regions remains a fundamental question. Embryonic Xenopus was
      previously used to identify juxtaposed embryonic cells that first express
      proopiomelanocortin mRNA in forebrain and pituitary, supporting the idea that
      this neuropeptide phenotype is induced locally (Hayes and Loh, 1990, Development
      110: 747-757). To begin to examine how a more widespread population of forebrain
      cells is set up, the present focus is on the thyrotropin-releasing hormone (TRH)
      phenotype. Serial section in situ hybridization histochemistry produced the
      unexpected finding that the adult-like TRH system spanning forebrain and
      comprising over six different telencephalic and diencephalic nuclei, is preceded
      by an embryonic TRH cell population that is initially localized and then highly
      regionalized in the area from which the adult pattern develops. Thus, the first
      TRH cells, detected in vivo after 35h (stage 29/30), were confined to discrete
      anterior or posterior bilateral clusters in embryonic forebrain or hindbrain.
      Thereafter, the TRH cell clusters in diencephalon, but not hindbrain, expanded to
      form rows, extending anteriorly into telencephalon and bifurcating posteriorly
      around the infundibulum. By 80 h (stage 42), after extensive brain morphogenesis,
      these forebrain rows showed regional differences in levels of TRH mRNA
      corresponding to the specific brain nuclei that have been shown to contain TRH
      cells in adult. These findings show that subsets of phenotype-specific forebrain
      cells first form a regionalized neuronal cell fate before distinct brain nuclei
      form. This in turn points to the testable hypothesis in Xenopus that certain
      neuronal cell fates in forebrain may be dictated by cell lineage or local
      induction.

PMID- 7815067
TI  - Responses of thoracic interneurons to tactile stimulation in cockroach,
      Periplaneta americana.
AB  - Recent findings indicate that cockroaches escape in response to tactile
      stimulation as well as they do in response to the classic wind puff stimulus. The
      thoracic interneurons that receive inputs from ventral giant interneurons also
      respond to tactile stimulation and, therefore, represent a potential site of
      convergence between wind and tactile stimulation, as well as other sensory
      modalities. In this article, we characterize the tactile response of these
      interneurons, which are referred to as type-A thoracic interneurons (TIAs). In
      response to tactile stimulation of the body cuticle, TIAs typically respond with
      a short latency biphasic depolarization which often passes threshold for action
      potentials. The biphasic response is not typical of responses to wind stimulation
      nor of tactile stimulation of the antennae. It is also not seen in tactile
      responses of thoracic interneurons that are not part of the TIA group. The
      responses of individual TIAs to stimulation of various body locations were
      mapped. The left-right directional properties of TIAs are consistent with their
      responses to wind puffs from various different directions. Cells that respond
      equally well to wind from the left and right side also respond equally well to
      tactile stimuli on the left and right side of the animal's body. In contrast,
      cells that are biased to wind on one side are also biased to tactile stimulation
      on the same side. In general, tactile responses directed at body cuticle are
      phasic rather than tonic, occurring both when the tactile stimulator is depressed
      and released. The response reflects stimulus strength and follows repeated
      stimulation quite well. However, the first phase of the biphasic response is more
      robust during high-frequency stimulation than the second phase. TIAs also respond
      to antennal stimulation. However, here the response characteristics are
      complicated by the fact that movement of either antenna evokes descending
      activity in both left and right thoracic connectives. The data suggest that the
      TIAs make up a multimodal site of sensory convergence that is capable of
      generating an oriented escape turn in response to any one of several sensory
      cues.

PMID- 7815068
TI  - Regulation of SC1/DM-GRASP during the migration of motor neurons in the chick
      embryo brain stem.
AB  - The hindbrain of the chick embryo contains three classes of motor neurons:
      somatic, visceral, and branchial motor. During development, somata of neurons in
      the last two classes undergo a laterally directed migration within the
      neuroepithelium; somata translocate towards the nerve exit points, through which
      motor axons are beginning to extend into the periphery. All classes of motor
      neuron are immunopositive for the SC1/DM-GRASP cell surface glycoprotein. We have
      examined the relationship between patterns of motor neuron migration, axon
      outgrowth, and expression of the SC1/DM-GRASP mRNA and protein, using anterograde
      or retrograde axonal tracing, immunohistochemistry, and in situ hybridization. We
      find that as motor neurons migrate laterally, SC1/DM-GRASP is down-regulated,
      both on neuronal somata and axonal surfaces. Within individual motor nuclei,
      these lateral, more mature neurons are found to possess longer axons than the
      young, medial cells of the population. Labelling of sensory or motor axons
      growing into the second branchial arch also shows that motor axons reach the
      muscle plate first, and that SC1/DM-GRASP is expressed on the muscle at the time
      growth cones arrive.

PMID- 7815069
TI  - Muscarinic acetylcholine responses in the early embryonic chick retina.
AB  - The action of acetylcholine on cytoplasmic Ca2+ concentration ([Ca2+]i) was
      studied in early embryonic chick retinae. Whole neural retinae were isolated from
      embryonic day 3 (E3) chicks and loaded with a Ca(2+)-sensitive fluorescent dye
      (Fura-2). Increases in [Ca2+]i were evoked by the puff application of
      acetylcholine at concentrations higher than 0.1 microM. The Ca2+ response became
      larger in a dose-dependent manner up to 10 microM of acetylcholine applied. The
      rise in [Ca2+]i was not due to the influx of Ca2+ through calcium channels, but
      to the release of Ca2+ from internal stores. A calcium channel antagonist,
      nifedipine, which completely blocks the Ca2+ rise caused by depolarization with
      100 mM K+, had no effects on the acetylcholine response and the Ca2+ response to
      acetylcholine occurred even in a Ca(2+)-free medium. The Ca2+ response to
      acetylcholine was mediated by muscarinic receptors. Atropine of 1 microM
      abolished the response to 10 microM acetylcholine, whereas d-tubocurarine of 100
      microM had no effects. Two muscarinic agonists, muscarine and carbamylcholine
      (100 microM each), evoked comparable responses with that to 10 microM
      acetylcholine. The developmental change of the muscarinic response was examined
      from E3 to E13. The Ca2+ response to 100 microM carbamylcholine was intense at E3
      E5, then rapidly declined until E8. The muscarinic Ca2+ mobilization we found in
      the early embryonic chick retina may be regarded as a part of the "embryonic
      muscarinic system" proposed by Drew's group, which appears transiently and
      ubiquitously at early embryonic stages in relation to organogenesis.

PMID- 7815070
TI  - Lateralization and motor stereotypy of song production in the brown-headed
      cowbird.
AB  - Song production in adult brown-headed cowbirds (Molothrus ater ater) is
      lateralized, with a slight right syringeal dominance. The left side of the syrinx
      produces low-frequency (200-2000 Hz) notes within the introductory note clusters,
      while the right side produces the higher-frequency (1500-6000 Hz) introductory
      notes, the interphrase unit (10-12 kHz), and the final high-frequency whistle (5
      13 kHz). Cross-correlation analyses reveal that individual cowbirds produce each
      of their four to seven song types with a distinct stereotyped motor pattern--as
      judged by the patterns of syringeal airflow and subsyringeal pressure. The
      acoustic differences across song types are reflected in the differences in the
      bronchial airflow and air sac pressure patterns associated with song production.
      These motor differences are particularly striking within the second and third
      introductory note clusters where there is a rapid switching back and forth
      between the two sides of the syrinx in the production of notes. These motor
      skills may be especially important in producing behaviorally effective song.

PMID- 7815071
TI  - Re-evaluation of the absolute threshold and response mode of the most sensitive
      known "vibration" detector, the cockroach's subgenual organ: a cochlea-like
      displacement threshold and a direct response to sound.
AB  - Earlier accounts claim from indirect measurements that the subgenual organ (SGO)
      in the proximal tibia of the cockroach leg can detect vibrational displacements
      down to 0.002 nm, two orders of magnitude below the threshold for vertebrate hair
      cells in the cochlea. The SGO vibration threshold is redetermined here more
      directly by a new method on a cantilever beam, while controlling for particular
      acoustic and vibrational artifacts that might have compromised earlier efforts.
      The threshold is revised upwards to about 0.2 nm in the most sensitive
      preparation, about the same as the cochlea. Recently, it has been determined that
      the cockroach SGO also has an auditory response, and the data here on
      subthreshold summation and response-intensity relationships provide further
      evidence that sound and contact vibration are both sensed by the same receptor
      neurons. Direct measurements rule out the prevailing hypothesis that sound is
      detected indirectly as induced vibration of the ground, and also weigh strongly
      against any significant involvement of generalized leg resonance in acoustic pick
      up. The results fit with a recent proposal that the auditory response is direct,
      and that acoustic fluctuations inside the tracheae may be the primary response
      mode in the transduction of both vibration and sound.

PMID- 7815072
TI  - Ependymal reactions to injury. A review.
AB  - The ependyma reacts to injury with a few stereotypical responses and does not
      regenerate at any age. Non-neoplastic ependymal cells do not undergo mitotic
      proliferation and do not re-express fetal cytoskeletal or secretory proteins.
      Atrophy of ependymal cells accompanies generalized cerebral atrophy. The ependyma
      may be damaged by stretching during ventricular dilatation, by infarcts of the
      ventricular wall or by infection and inflammation. Tearing of the epithelium
      leaves discontinuities that become filled with processes of subventricular
      astrocytes. In some cases reactive gliosis is minimal, but in most it is
      extensive and gliotic nodules form beneath intact ependyma and within gaps
      between ependymal islands. Ependymal rosettes may form in several ways:
      sequestration of diverticuli from the surface; curling of a torn edge or
      penetration of an edge into the parenchyma; reactive gliosis overgrowing an
      ependymal edge; in situ differentiation of ependymal cells from deep
      neuroepithelial cells. Migration and metaplasia are unlikely mechanisms.
      Bacterial and fungal ependymitis are highly destructive. Several viruses,
      especially mumps, selectively infect ependymal cells and are an important cause
      of acquired aqueductal stenosis without inflammation. Damaged ependyma may not be
      able to perform its function in the regulation of transport of fluid, ions and
      small molecules between cerebral parenchyma and ventricular fluid and thus may
      contribute to hydrocephalus. Damage to the fetal ependyma may result in secondary
      focal dysplasias of the developing brain.

PMID- 7815073
TI  - Early loss of neostriatal striosome neurons in Huntington's disease.
AB  - During the first years of symptomatic Huntington's disease (HD), no readily
      apparent pathology is seen in the neostriatum at autopsy. To investigate the
      pathological correlates of chorea and other early clinical signs, we examined the
      evolution of neuronal loss and accompanying astrocytosis in neostriatal tissue
      from autopsy cases of early HD. We found scattered islands of astrocytosis and
      neuronal loss that were present before the previously described ventrally
      progressive wave of generalized neuronal loss. Histological demonstration of
      these islands, which are apparently specific to HD, is very helpful in the
      pathological differential diagnosis of this disease. Immunocytochemical stains
      for glial fibrillary acidic protein and for markers of the neostriatal striosome
      matrix system showed that these islands correspond to the striosome compartment.
      Striosomal neuronal loss was present throughout the dorsoventral extent of the
      caudate nucleus and putamen during the early phase of symptomatic disease, and
      this loss extended to the most ventral region of the nucleus accumbens in later
      stages. Analysis of the functional circuitry of the basal ganglia suggests that
      early degeneration of striosomal neurons may produce hyperactivity of the
      nigrostriatal dopaminergic pathway, causing chorea and other early clinical
      manifestations of HD.

PMID- 7815074
TI  - Macrophage-released factor stimulates selectively myogenic cells in primary
      muscle culture.
AB  - Myofibers are reconstituted by the proliferation and fusion of muscle precursor
      cells when skeletal muscle is injured. One of the critical events is the peak
      accumulation of macrophages after 48 hours at the damage site before the
      satellite cell proliferation. In addition to their well-known role as a scavenger
      cell, there is now direct evidence of a mitogenic role of macrophages in
      regenerating muscle. We have utilized an in vitro model to directly investigate
      and prove that macrophages increase myoblast growth not only of satellite cells,
      but also of primary myoblasts. Rat muscle cells were cultured in the presence or
      absence of exudate macrophages obtained by peritoneal washing after
      thioglycollate broth injection. Macrophage coculture increases several times the
      myoblasts/myotubes yield. This effect is particularly evident in muscle culture
      conditions in which fibroblast growth is predominant over myoblast proliferation,
      suggesting a myoblast selective mitogenic effect of macrophages. The results are
      confirmed by quantitative analyses of both DNA and skeletal muscle-specific
      contractile proteins by gel electrophoresis and immunocytochemistry. Experiments
      with macrophage-conditioned media show this effect is mediated by soluble
      factors. This growth factor-like activity, which has been shown to be acid-stable
      and heat-labile, labile, exerts its effects not only on specialized satellite
      cells during muscle regeneration, but also has a broader mitotic activity on all
      myogenic cells. In view of the role of muscle regeneration in muscle diseases and
      of the perspectives offered by gene therapy via myoblasts, we strongly believe
      that our results open new opportunities in removing many of the clinical
      constraints associated with repair and cell transplantation.

PMID- 7815075
TI  - Interlaboratory comparison of neuropathology assessment in Alzheimer's disease.

PMID- 7815076
TI  - Localization of tissue inhibitor of matrix metalloproteinases in Alzheimer's
      disease and normal brain.
AB  - Based upon the hypothesis that metalloproteinases and their inhibitors might be
      involved in the pathogenesis of Alzheimer's disease, we studied brain samples of
      eight cases of Alzheimer's disease, six other pathological entities and three
      elderly controls for tissue inhibitor of metalloproteinase (TIMP)
      immunoreactivity. Specificity was supported by a loss of immunoreactivity
      following antigen preabsorption of antisera. Areas studied included ependyma,
      choroid plexus, frontoparietal, hippocampal and cerebellar cortex, n. basalis of
      Meynert, basal ganglia, midbrain, pons, and medulla. TIMP positivity was
      localized to neuritic senile plaques, neurofibrillary tangles and Purkinje cells.
      The pattern of TIMP plaque staining was similar to that observed with anti tau
      and SP18 antibodies. It differed from that observed with anti SP40, HAM 56 and
      GFAP antibodies. The selective localization of TIMP to the neuritic lesions of
      Alzheimer's disease in a codistribution with the amyloid precursor protein and
      abnormally phosphorylated and truncated tau supports a possible role for
      metalloproteinases and their inhibitors in the evolution of these lesions.

PMID- 7815077
TI  - Differences in diaphragm fiber types in SIDS infants.
AB  - The diaphragm is a vital respiratory muscle in the sleeping infant. Any changes
      in diaphragm fiber type number or size could represent either a primary
      developmental delay or a secondary reaction to increased workload, and could give
      a clue as to the pathogenesis of sudden infant death syndrome (SIDS). We
      therefore quantitated by point counting on ATPase histochemistry the numbers and
      areas of type 1 and 2 fibers in the diaphragm, external intercostal and psoas
      muscles of 37 SIDS and 20 control infants. The amount of slow, fast and fetal
      myosin in the diaphragm and psoas muscles was measured by electrophoresis to
      check the ATPase quantitation. There were fewer type 1 fibers in SIDS (median
      30.0%) compared with control (median 40.0%) infants (p < 0.02), whereas the
      diameter of type 1 fibers in SIDS (median 33.9 microns) was larger than in
      control (median 30.3 microns) infants (p < 0.007). The total cross-sectional area
      occupied by type 1 and 2 fibers was similar in both groups. No changes were found
      in the external intercostal or psoas. The amount of slow and fast myosins
      correlated well with type 1 and type 2 fibers, respectively. The finding of fewer
      type 1 (fatigue-resistant) fibers of large diameter in SIDS diaphragms suggests
      that differences in muscle fiber types may predispose these infants to diaphragm
      fatigue and respiratory failure.

PMID- 7815078
TI  - Functional alterations in Alzheimer's disease: decreased glucose transporter 3
      immunoreactivity in the perforant pathway terminal zone.
AB  - Positron emission tomography (PET) studies measuring glucose utilization have
      demonstrated cerebral hypometabolism in Alzheimer's disease (AD). The anatomic
      and biochemical basis for this observation remains unknown. We have examined the
      distribution in the hippocampal formation of the neuron-specific glucose
      transporter 3 (Glut3) protein. Using quantitative immunohistochemistry, we find a
      large reduction (49.5%) in Glut3 immunoreactivity in the outer portion of the
      molecular layer of the dentate gyrus in AD brains. This region corresponds to the
      terminal zone of the perforant pathway, whose cells of origin in layer II of the
      entorhinal cortex are selectively destroyed in AD. Because glucose uptake
      reflects metabolic demand, these results suggest a decrement of functional
      activity in the deafferented dentate gyrus granule cells. Generalizing from this
      observation, decreased glucose uptake seen on PET studies may reflect, in part,
      decreased glucose transport and utilization in functionally deafferented cortical
      fields.

PMID- 7815079
TI  - An improved approach to prepare human brains for research.
AB  - We describe two protocols for preparing human brains collected for research and
      diagnosis. In both protocols, one half brain is processed for research and the
      other for neuropathological evaluation. Clinical, neuropathological and tissue
      mRNA retention data are used for sample categorization. In protocol 1, coronal,
      whole hemisphere slices cut at standardized landmarks are frozen with a cooling
      device at -90 degrees C, which yields discrete anatomical structures. In selected
      instances, small blocks of brain are frozen at -160 degrees C in liquid nitrogen
      vapor. Cooling device or liquid nitrogen vapor frozen samples are suitable for in
      situ hybridization, protein blotting or immunohistochemistry. Morphological
      freezing artifacts are minimal. In protocol 2, one half brain is frozen en bloc
      on dry ice; this tissue is suitable for regional evaluation of gene expression or
      neurochemistry. Morphological freezing artifacts are severe. In both protocols,
      the other half brain is fixed in formalin prior to sectioning and diagnostic
      evaluation. The standardized selection of paraffin blocks from each brain allows
      precise diagnoses to be established, including identification of dangerous
      infectious processes; moreover, it makes it possible to produce a set of
      uniformly selected blocks and slides for comparative studies. These protocols
      lead to standardized tissue preparation for research and reduce variables
      impairing interpretation and comparison of data.

PMID- 7815080
TI  - Reliability of differential PCR for the detection of EGFR and MDM2 gene
      amplification in DNA extracted from FFPE glioma tissue.
AB  - A series of 43 human gliomas, consisting of 30 glioblastomas, 7 anaplastic
      astrocytomas, 3 low grade astrocytomas, 2 ependymomas, and 1 oligodendroglioma,
      was studied for amplification of the epidermal growth factor receptor (EGFR) and
      mouse double minute 2 (MDM2) genes. DNA extracted from formalin-fixed, paraffin
      embedded tissue sections was analyzed by differential PCR and the results were
      compared with slot blot examination of DNA extracted from frozen tissue from the
      same neoplasms. Twelve glioblastomas (40%) showed amplification of the EGFR gene,
      and overexpression of EGFR was evident in each of these tumors as indicated by
      the immunoperoxidase technique. Two of the tumors with EGFR gene amplification
      also revealed amplification of the MDM2 gene, while one additional glioblastoma
      revealed MDM2 amplification only. A 100% concordance in the detection of
      amplification was observed between differential PCR and slot blot analysis;
      consequently, these results indicate that differential PCR using DNA extracted
      from archival tissue sections is a reliable method of demonstrating gene
      amplifications in glial tumors.

PMID- 7815081
TI  - Alterations at chromosome 17 loci in peripheral nerve sheath tumors.
AB  - Little is known about the molecular genetic changes in malignant peripheral nerve
      sheath tumors (MPNST). Inactivation of the TP53 gene in 17p has been reported in
      a few tumors. The MPNST is one of the manifestations of neurofibromatosis 1
      (NF1), suggesting that the NF1 gene in 17q might be important. We present a study
      of 15 neurofibromas and MPNST from nine individuals. Seven patients had NF1, and
      six of these developed MPNST. Genetic alterations at nine polymorphic loci on
      chromosome 17 were examined. Allelic imbalance was detected only in the malignant
      tumors from NF1 patients (4/6). Complete loss of heterozygosity of 17q loci was
      found in three of these tumors, all including loci within the NF1 gene. Two of
      the malignant tumors also showed deletions on 17p. No mutations were detected
      within exon 5-8 of the TP53 in any of the MPNST, and none of them were TP53
      protein-positive using immunostaining with mono- and polyclonal antibodies
      against TP53. The numbers of chromosome 17 present in each tumor were evaluated
      by use of fluorescence in situ hybridization (FISH) on interphase nuclei with a
      centromere-specific probe. A deviation from the disomic status of chromosome 17
      was observed in two of the MPNST from NF1 patients. These results support the
      hypothesis of inactivation of both NF1 gene alleles during development of MPNST
      in patients with NF1. In contrast to other reports, we did not find evidence for
      a homozygous mutated condition of the TP53 gene in the same tumors. Finally, FISH
      analysis was in accordance with the DNA analysis in the deduction of the numbers
      of chromosome 17 in these tumors.

PMID- 7815082
TI  - Neuronal changes in the substantia nigra with aging: a Golgi study.
AB  - In order to recognize substantia nigra neuronal changes occurring in aging, 20
      human control brains from 13 males and 7 females with a mean age of 61 years
      (range 20 to 93 years) without neurological disease were examined using the Golgi
      method. A quantitative study of dendrites and dendritic spines was performed as
      well as a statistical analysis of obtained data. Parallel sections to the
      impregnated material were histologically and immunohistologically studied with
      the aim to identify possible neuronal cytoskeletal abnormalities. Results were
      compared to changes of substantia nigra reported in other conditions such as
      Parkinson's disease (PD) and methyl-4-phenylpyridine (MPTP) experimental
      toxicity. Three different substantia nigra neuronal types were observed.
      Morphological changes during aging consisted of distorted profile of the cell
      body and swelling and beading of dendritic branches. The quantitative assessment
      of changes observed in neuronal types showed a significant loss of dendrites and
      dendritic spines, especially in the oldest cases. These findings were similar to
      those previously described in other cerebral areas during aging, but a specific
      vulnerability of the largest substantia nigra neuronal type could be observed.
      Nodulations and beaded aspects of dendrites are reminiscent of those changes
      previously described in MPTP toxicity. Dendritic varicosities found in the oldest
      cases have also been found in dendrites of large substantia nigra neurons in PD.
      Cytoskeletal abnormalities have been described in PD but were not found in the
      present study. Therefore, other pathophysiological mechanisms different from the
      cytoskeletal compromise occurring in some neurodegenerative diseases should be
      involved in aging.

PMID- 7815083
TI  - Sensitivity to 2,5-hexanedione of neurofilaments in neuroblastoma cell line SK-N
      SH increases during differentiation.
AB  - The effect of 2,5-hexanedione (2,5-HD) on the distribution of the neurofilamental
      (NF) proteins and vimentin was examined in human neuroblastoma cell line SK-N-SH
      with immunocytochemical methods. Retinoic acid (10 microM) induced
      differentiation into neuronal cells resulting in the outgrowth of processes and
      synthesis of NF proteins in the majority of the cells. A minority (4%)
      differentiated as large fibroblasts. Cells were exposed to 0-10 mM 2,5-HD for 3
      days. In neuronal cells a concentration-dependent accumulation of NF proteins was
      detected as a spherical structure in the perikaryon. Neurofilaments in
      differentiated SK-N-SH cells were more susceptible to 2,5-HD than NF in
      undifferentiated cells, as the effects were observed at much lower 2,5-HD
      concentrations. In contrast, no accumulation of vimentin was detected in the
      fibroblastic cells.

PMID- 7815084
TI  - Shared allelic losses on chromosomes 1p and 19q suggest a common origin of
      oligodendroglioma and oligoastrocytoma.
AB  - Loss of heterozygosity (LOH) in specific chromosomal regions, which are likely to
      harbor tumor suppressor genes, has been associated with human gliomas. In this
      study we have analyzed astrocytic and oligodendroglial tumors for LOH on
      chromosomes 1 and 19. By microsatellite analysis LOH was found on chromosome arm
      1p in 6/15 oligodendrogliomas WHO grade II and III, 12/25 oligoastrocytomas WHO
      grade II and III, 6/79 glioblastomas WHO grade IV, 5/44 astrocytomas WHO grade II
      and III and 0/23 pilocytic astrocytomas WHO grade I. The high incidence of LOH on
      chromosome arm 1p in oligodendrogliomas and oligoastrocytomas indicates that a
      putative tumor suppressor gene in this region is involved in the formation of
      gliomas with oligodendroglial features. Furthermore, the frequent involvement of
      chromosome arm 1p in oligodendrogliomas and oligoastrocytomas, but not in
      astrocytomas, suggests that genetically oligoastrocytoma is more similar to
      oligodendroglioma than to astrocytoma. In order to support this hypothesis,
      oligodendroglial and astrocytic areas in three mixed oligoastrocytomas were
      examined differentially for LOH 1p and for LOH 19q, the second genetic region
      believed to be affected in these tumors. All three tumors had LOH of 1p and LOH
      of 19q in both areas of oligodendroglial and of astrocytic differentiation. These
      findings show that the astrocytic and oligodendroglial portions of
      oligoastrocytoma share molecular genetic features and probably are of monoclonal
      origin.

PMID- 7815085
TI  - Structural basis of neuron-to-neuron cross-excitation in dorsal root ganglia.
AB  - Lanthanum was used as a tracer substance to determine whether small molecules in
      the bulk extracellular space in dorsal root ganglia have access to the narrow
      cleft that separates sensory neurons from their surrounding satellite cell
      sheath. Results showed that lanthanum is able to diffuse into this cleft,
      especially when the tissue is incubated with the tracer before fixation.
      Lanthanum gained access to the cleft at the seam where adjacent satellite cell
      processes meet. There appears to be preferential access in the axon hillock
      initial segment region. Large diameter light neurons, which generally support
      fast conducting myelinated axons and carry information about non-nociceptive
      sensory events, proved more likely to admit lanthanum than small diameter dark
      neurons, which tend to have thin myelinated and unmyelinated axons and typically
      carry nociceptive information. Peripheral axotomy triggered a reduction in the
      access of lanthanum to the neuron-satellite cell cleft. These data bear on the
      mechanism of non-synaptic cell-to-cell cross-excitation within dorsal root
      ganglia, and in particular, lend support to the hypothesis that this interaction
      is mediated chemically rather than electrically.

PMID- 7815086
TI  - Effect of retinal impulse blockage on cytochrome oxidase-poor interpuffs in the
      macaque striate cortex: quantitative EM analysis of neurons.
AB  - One of the hallmarks of the primate striate cortex is the presence of cytochrome
      oxidase-rich puffs in its supragranular layers. Neurons in puffs have been
      classified as type A, B, and C in ascending order of cytochrome oxidase content,
      with type C cells being the most vulnerable to retinal impulse blockade. The
      present study aimed at analysing cytochrome oxidase-poor interpuffs with
      reference to their metabolic cell types and the effect of intraretinal
      tetrodotoxin treatment. The same three metabolic types were found in interpuffs,
      except that type B and C neurons were smaller and less cytochrome oxidase
      reactive in interpuffs than in puffs. Type A neurons had small perikarya, low
      levels of cytochrome oxidase, and received exclusively symmetric axosomatic
      synapses. The largest neurons were pyramidal, type B cells with moderate
      cytochrome oxidase activity and were also contacted exclusively by symmetric
      axosomatic synapses. Type C cells medium-sized with a rich supply of large,
      darkly reactive mitochondria and possessed all the characteristics of GABAergic
      neurons. They were the only cell type that received both symmetric and asymmetric
      axosomatic synapses. Two weeks of monocular tetrodotoxin blockade in adult
      monkeys caused all three major cell types in deprived interpuffs to suffer a
      significant downward shift in the size and cytochrome oxidase reactivity of their
      mitochondria, but the effects were more severe in type B and C neurons. In
      nondeprived interpuffs, all three cell types gained both in size and absolute
      number of mitochondria, and type A cells also had an elevated level of cytochrome
      oxidase, indicating that they might be functioning at a competitive advantage
      over cells in deprived columns. However, type B and C neurons showed a net loss
      of darkly reactive mitochondria, indicating that these cells became less active.
      Thus, mature interpuff neurons remained vulnerable to retinal impulse blockade
      and the metabolic capacity of these cells remains tightly regulated by neuronal
      activity.

PMID- 7815087
TI  - Imaging myelinated nerve fibres by confocal fluorescence microscopy: individual
      fibres in whole nerve trunks traced through multiple consecutive internodes.
AB  - Current methods of morphological analysis do not permit detailed imaging of
      individual myelinated fibres over substantial lengths without disruption of
      neighbouring, potentially significant, cellular and extracellular relationships.
      We report a new method which overcomes this limitation by combining aldehyde
      induced fluorescence with confocal microscopy. Myelin fluorescence was intense
      relative to that from other tissue components, enabling individual myelinated
      nerve fibres to be traced for distances of many millimeters in whole PNS nerve
      trunks. Image obtained with a Bio-Rad MRC-600 confocal laser scanning microscope
      clearly displayed features of PNS and CNS myelinated fibres including nodes of
      Ranvier; fibre diameter; sheath thickness and contour; branch points at nodes; as
      well as (in the PNS) Schmidt-Lanterman incisures and the position of Schwann cell
      nuclei. Direct comparisons using the same specimens (whole nerve trunks; also
      teased fibres) showed confocal imaging to be markedly superior to conventional
      fluorescence microscopy in terms of contrast, apparent resolution and resistance
      to photobleaching. Development of the fluorophore was examined systemically in
      sciatic nerves of young adult rats. In separate experiments, animals were
      perfused systemically using (1) 5% glutaraldehyde; (2) Karnovsky's solution; (3)
      4% paraformaldehyde; buffered with either 0.1 M sodium phosphate or sodium
      cacodylate (pH 7.4). The concentration of glutaraldehyde in the fixative solution
      was the principal determinant of fluorescence intensity. Confocal imaging was
      achieved immediately following perfusion with 5% glutaraldehyde or Karnovsky's.
      Fluorescence intensity increased markedly during overnight storage in these
      fixatives and continued to increase during subsequent storage in buffer alone.
      The fluorophore was stable and resistant to fading during storage (15 months at
      least), enabling data collection over extended periods. To demonstrate
      application of the method in neuropathology, individual fibres in transected
      sciatic nerve trunks were traced through multiple successive internodes:
      Classical features of Wallerian degeneration (axonal swelling and debris; ovoid
      formation and incisure changes; variation among fibres in the extent of
      degeneration) were displayed. The method is compatible with subsequent
      ultrastructural examination and will complement existing methods of investigation
      of myelinated fibre anatomy and pathology, particularly where preservation of 3
      dimensional relationships or elucidation of spatial gradients are required.

PMID- 7815088
TI  - An immunocytochemical investigation of glial morphology in the Pacific hagfish:
      radial and astrocyte-like glia have the same phylogenetic age.
AB  - This study attempts to reconstruct the early phylogenetic history of macroglial
      cells among craniates. Since glia does not fossilize, such a reconstruction must
      be based on a cladistic comparison of glial characters in the Recent craniate
      taxa (hagfishes, lampreys, and gnathostomes); however, there are only few data on
      glial morphology and none on glial immunocytochemistry in hagfishes. Therefore,
      we investigated the presence and localization of various macroglia-specific
      epitopes in the brain and spinal cord of the Pacific hagfish, Eptatretus stouti
      (Myxinoidea) by means of immunocytochemistry. Antibodies directed against S100
      protein and vimentin showed no cross reactivity. Antibodies directed against
      glial fibrillary acidic protein and glutamine synthetase labelled various glial
      structures. Glial fibrillary acidic protein-like immunoreactivity was observed in
      ependymal cells with radially oriented processes in some regions. However,
      throughout the entire CNS, labelling of non-ependymal cells and their processes
      prevailed. The processes of these cells made occasional vascular contacts and
      they also made contacts with neuronal perikarya. Glutamine synthetase-like
      immunoreactivity was also found in some processes with radial orientation and in
      ependymal cells; but the antibody stained mainly non-ependymal cells which gave
      rise to a felt-like meshwork of interdigitating fine and very fine processes
      penetrating the neuropil of the entire brain. Additionally, there was labelling
      in the walls of blood vessels and in processes enwrapping individual neurons. The
      occurrence of glial fibrillary acidic protein- and glutamine synthetase-like
      immunoreactivity in non-ependymal glial elements in the brain of hagfishes and
      the relative scarcity of labelling in radial glial elements necessitates a re
      interpretation of the evolutionary history of glial cells. Non-ependymal
      macroglia with immunocytochemical and morphological characters resembling typical
      (mammalian) astrocytes appears to be as primitive as the various forms of radial
      ependymal glia.

PMID- 7815089
TI  - GREEN: a program package for docking studies in rational drug design.
AB  - A program package, GREEN, has been developed that enables docking studies between
      ligand molecules and a protein molecule. Based on the structure of the protein
      molecule, the physical and chemical environment of the ligand-binding site is
      expressed as three-dimensional grid-point data. The grid-point data are used for
      the real-time evaluation of the protein-ligand interaction energy, as well as for
      the graphical representation of the binding-site environment. The interactive
      docking operation is facilitated by various built-in functions, such as energy
      minimization, energy contribution analysis and logging of the manipulation
      trajectory. Interactive modeling functions are incorporated for designing new
      ligand molecules while considering the binding-site environment and the protein
      ligand interaction. As an example of the application of GREEN, a docking study is
      presented on the complex between trypsin and a synthetic trypsin inhibitor. The
      program package will be useful for rational drug design, based on the 3D
      structure of the target protein.

PMID- 7815090
TI  - Nucleotide-binding properties of adenylate kinase from Escherichia coli: a
      molecular dynamics study in aqueous and vacuum environments.
AB  - The complex of adenylate kinase with its transition-state inhibitor has been
      studied by molecular dynamics simulations in water and in vacuum environments
      with the GROMOS force field over a period of 300 ps. The adenylate kinase, a
      member of the nucleotide-binding protein family, was exemplarily chosen for the
      inspection of the nucleotide-binding properties in the active site. The ligand
      binding and the domain movements have been studied in detail over the simulation
      period and compared with the crystal structure. Secondary structure transitions
      and domain closures defined those parts of the structure which are involved in an
      induced-fit movement of the enzyme. The presence of more stable hydrogen bonds on
      the substrate side leads to the assumption that substrate binding is more
      specific than cosubstrate binding. Reliable results were achieved only if water
      was explicitly included in the stimulation.

PMID- 7815091
TI  - Active-site mobility inhibits reductive dehalogenation of 1,1,1-trichloroethane
      by cytochrome P450cam.
AB  - Recent studies by Wackett and co-workers have shown that cytochrome P450cam is
      capable of reductively dehalogenating hexachloroethane at a significant rate, but
      that no appreciable dehalogenation of 1,1,1-trichloroethane is observed. A
      growing body of evidence indicates that differences in intrinsic reactivity can
      not completely explain this observation. We therefore explored the possible role
      of differences in preferred binding orientation and in active-site mobility. A
      detailed analysis of molecular dynamics trajectories with each of these
      substrates bound at the active site of P450cam is presented. While the dynamics
      and overall time-average structure calculated for the protein are similar in the
      two trajectories, the two substrates behave quite differently. The smaller
      substrate, 1,1,1-trichloroethane, is significantly more mobile than
      hexachloroethane and has a preferred orientation in which the substituted carbon
      is generally far from the heme iron. In contrast, for hexachloroethane, one of
      the chlorine atoms is nearly always in van der Waals contact with the heme iron,
      which should favor the initial electron transfer step.

PMID- 7815092
TI  - Quantitative structure-activity relationships by neural networks and inductive
      logic programming. I. The inhibition of dihydrofolate reductase by pyrimidines.
AB  - Neural networks and inductive logic programming (ILP) have been compared to
      linear regression for modelling the QSAR of the inhibition of E. coli
      dihydrofolate reductase (DHFR) by 2,4-diamino-5-(substituted benzyl)pyrimidines,
      and, in the subsequent paper [Hirst, J.D., King, R.D. and Sternberg, M.J.E. J.
      Comput.-Aided Mol. Design, 8 (1994) 421], the inhibition of rodent DHFR by 2,4
      diamino-6,6-dimethyl-5-phenyl-dihydrotriazines. Cross-validation trials provide a
      statistically rigorous assessment of the predictive capabilities of the methods,
      with training and testing data selected randomly and all the methods developed
      using identical training data. For the ILP analysis, molecules are represented by
      attributes other than Hansch parameters. Neural networks and ILP perform better
      than linear regression using the attribute representation, but the difference is
      not statistically significant. The major benefit from the ILP analysis is the
      formulation of understandable rules relating the activity of the inhibitors to
      their chemical structure.

PMID- 7815093
TI  - Quantitative structure-activity relationships by neural networks and inductive
      logic programming. II. The inhibition of dihydrofolate reductase by triazines.
AB  - One of the largest available data sets for developing a quantitative structure
      activity relationship (QSAR)--the inhibition of dihydrofolate reductase (DHFR) by
      2,4-diamino-6,6-dimethyl-5-phenyl-dihydrotriazine derivatives--has been used for
      a sixfold cross-validation trial of neural networks, inductive logic programming
      (ILP) and linear regression. No statistically significant difference was found
      between the predictive capabilities of the methods. However, the representation
      of molecules by attributes, which is integral to the ILP approach, provides
      understandable rules about drug-receptor interactions.

PMID- 7815094
TI  - Rational design of novel neurotensin mimetics: discovery of a pharmacologically
      unprecedented agent exhibiting concentration-dependent dual effects as antagonist
      and full agonist.
AB  - We report the rational design of novel neurotensin mimetics through use of the
      Multiple Template Approach. This approach is based on our notion that a flexible
      peptide can be replaced by a partially flexible molecule, identified through
      testing a comparatively small number of molecules possessing a different
      intrinsic availability of conformations of the native peptide. The Multiple
      Template Approach has culminated in the discovery of a pharmacologically
      unprecedented agent, which behaves as a neurotensin antagonist at low
      concentration and as a full neurotensin agonist at high concentration.

PMID- 7815096
TI  - Chemometric QSAR studies of antifungal azoxy compounds.
AB  - Quantitative structure-activity relationships (QSARs) for 16 azoxy compounds with
      antifungal activity have been studied by the combined approach of a partial least
      squares method and factorial design. The PLS model equation suggested the
      structural requirements of two substituents. R1 and R2, for the antifungal
      activity. The sterically bulky and hydrophobic R1 substituents and electron
      withdrawing R2 substituents are favorable for the activity. We propose candidate
      compounds which are more potent than the compounds based on QSAR data. In this
      study, we show that the chemometric approach is a powerful tool for QSAR studies
      and drug design.

PMID- 7815095
TI  - A quantum-mechanical study of the chain-length dependent stability of the
      extended and 3(10)-helix conformations in dehydroalanine oligopeptides.
AB  - A quantum-chemical study of the chain-length dependent stability of the extended,
      2-ribbon and 3(10)-helix conformations in dehydroalanine (delta Ala)
      oligopeptides has been performed by using both semiempirical AM1 and ab initio 4
      31G methodologies. The validity of both methods in the study of the
      conformational properties of delta Ala oligopeptides was tested first on the
      dipeptide. The results of this test showed that 4-31G and AM1 calculations are in
      good agreement with 6-31G* calculations and experimental data. In order to
      monitor the conformational conversions, delta Ala oligopeptides comprising two to
      six residues were constructed. Molecular geometries were fully optimized using
      AM1, and the final conformations were verified to be minima by analysis of the
      corresponding second-derivative matrices. Conformational studies revealed that
      the 3(10)-helix is stabilized with respect to the 2(7)-ribbon when the number of
      residues is three or four, at the AM1 and ab initio 4-31G level respectively,
      while the extended form is the most stable in all the calculations performed. On
      the other hand, if a linear behaviour is assumed for longer chains, our
      calculations show a trend that would predict a conversion from extended form to
      3(10)-helix in oligopeptides with around six (ab initio 4-31G) or eight (AM1)
      delta Ala residues. In order to explain these conformational changes, the
      cooperative effects for the different conformers were investigated. Large
      cooperative energy effects were found for the 3(10)-helix conformation.

PMID- 7815097
TI  - A fast empirical method for the calculation of molecular polarizability.
AB  - A simple empirical method for the calculation of static molecular polarizability
      is described. The method is based on Slater's rules for the calculation of
      effective atomic nuclear shielding constants. The calculated molecular
      polarizabilities of a series of organic molecules correlated well (r = 0.98) with
      experimental measurements. Accurate calculated polarizabilities can be obtained
      rapidly by this method and may prove useful in deriving relationships between
      chemical structure and properties.

PMID- 7815098
TI  - Current methods for site-directed structure generation.
AB  - There has been a rapid growth of interest in techniques for site-directed drug
      design, fueled by the increasing availability of structural models of proteins of
      therapeutic importance, and by studies reported in the literature showing that
      potent chemical leads can be obtained by these techniques. Structure generation
      programs offer the prospect of discovering highly original lead structures from
      novel chemical families. Due to the fact that this technique is more-or-less
      still in its infancy, there are no case studies available that demonstrate the
      use of structure generation programs for site-directed drug design. Such programs
      were first proposed in 1986, and became commercially available in early 1992.
      They have shown their ability to reproduce, or suggest reasonable alternatives
      for, ligands in well-defined binding sites. This brief review will discuss the
      recent advances that have been made in the field of site-directed structure
      generation.

PMID- 7815099
TI  - Proliferative potential and prognostic evaluation of low-grade astrocytomas.
AB  - Despite their histological similarity, low-grade astrocytomas vary widely in
      their clinical behavior. To elucidate this variable behavior, we measured the
      proliferative potential of 69 primary and 18 recurrent low-grade astrocytomas and
      correlated the results with the clinical characteristics and outcome. Each
      patient received an intravenous infusion of bromodeoxyuridine (BUdR); BUdR
      labeled nuclei in excised tumor specimens were identified by immunoperoxidase
      staining. The BUdR labeling index (LI), or S-phase fraction, ranged from < 1 to
      9.3%; the LI was < 1% in 64 (74%) patients and > or = 1% in 23 patients (26%).
      The LI did not appear to be associated with age, sex, tumor location, or whether
      the tumor was primary or recurrent. A Cox proportional-hazards analysis of the
      influence of the LI and other variables (age, sex, tumor location, extent of
      surgery, primary versus recurrent tumor) on survival showed that the LI and
      extent of surgery (total resection, subtotal resection, biopsy) were significant
      in predicting both survival and progression-free survival for all patients and
      for patients with primary tumors. The LI was also significant in predicting
      progression-free survival for patients with recurrent tumors. The correlation
      between the BUdR LI and both survival and time to recurrence suggests that the
      outcome of low-grade astrocytomas varies according to the proliferative
      potential. The growth rate of these histologically similar tumors should be
      assessed individually in order to select specific treatment.

PMID- 7815100
TI  - Differential effects of methionine enkephalin on the growth of brain tumor cells.
AB  - The effect of methionine enkephalin on the growth of human brain tumor cells was
      investigated. The results show that this endogenous opioid has dual effects on
      tumor cell growth. This peptide exerted an inhibitory effect in SK-N-MC human
      neuroblastoma cell line; in contrast, in U-373 MG human astrocytoma cell line,
      the peptide showed a stimulatory effect. Treatment with naltrexone, an opioid
      receptor antagonist, also resulted in a similar alteration of tumor cell growth
      implicating that its action may be unrelated to opioid receptor blockade. These
      results suggest that in these tumor cell lines endogenous opioid systems may be
      involved in cell proliferation. Furthermore, these tumor cell lines may be useful
      model systems for the study of the signal transduction mechanisms of endogenous
      opioids.

PMID- 7815101
TI  - Detection of biological activity in the cerebrospinal fluid of patients with
      central nervous system tumors.
AB  - Tumor markers for brain tumors are important for initial diagnosis and monitoring
      of treatment. We used a modification of the phagokinetic track assay, which
      measures the migration of cells across a coverslip that is coated with colloidal
      gold, to assess whether the CSF from patients with brain tumors and other non
      neoplastic neurological disorders altered the migration of Balb/c 3T3
      fibroblasts. We found that CSF from patients with brain tumors stimulated the
      migration activity at a significantly higher level than did CSF from patients
      without tumors (mean migration activity: 65 +/- 9% for CSF from 113 patients with
      brain tumors; 14 +/- 4% for 44 patients with non-neoplastic CNS disease; and 9 +/
      1.2% for 54 patients with metabolic or other disorders). Thus the ability of CSF
      to stimulate migration of 3T3 cells appears to be a promising approach to
      detecting, understanding and following the activity of brain tumors.

PMID- 7815102
TI  - In vitro and in vivo cytotoxicity of gossypol against central nervous system
      tumor cell lines.
AB  - Gossypol is a lipid soluble polyphenolic compound isolated from cotton seed oil
      which has been previously shown to have antiproliferative activity in vitro
      against a variety of human solid tumor cell lines. It has been extensively tested
      in clinical trials as a male contraceptive agent and found to be well tolerated.
      Its mechanism of action is thought to be inhibition of cellular energy
      metabolism. It inhibits glycolysis through inhibition of LDH isoenzyme type 5,
      and it inhibits mitochondrial oxidative phosphorylation and electron transport.
      We tested the in vitro antiproliferative effect of gossypol against four well
      characterized human glioma cell lines, HS 683, U373, U87 and U138, and one rat
      glioma cell line, C6, using the colorimetric Microculture Tetrazolium Assay
      (MTT). Cytotoxicity was found to be concentration and time dependent and
      increased with incubation times up to 8 days. The relative sensitivity of the
      glioma cell lines to gossypol at 48 hour incubation correlated with their
      respective LDH isoenzyme profiles, with the more sensitive cell lines expressing
      increased cathodal LDH isoenzymes (LDH5). The in vitro cytotoxicity of gossypol
      to these CNS tumor lines was compared to the other non central nervous system
      solid tumor cell lines which had been previously reported as being sensitive to
      gossypol, including SW-13 (adrenal), MCF-7 (breast), T47-D (breast), and HeLa
      (cervical). Additional lines tested included SK-MEL-3 (melanoma), Colo 201
      (colon) and BRW, a line established in our laboratory from a patient with a
      Primitive Neuroectodermal tumor. C6, HS 683, and BRW had similar IC50s as the
      sensitive solid tumor cell lines. U373, U87 and U138 had significantly less
      sensitivity at 48 hours. There was greater cytotoxicity and no significant
      differences in the IC50s between any of cell lines at 8 day incubations.
      Additionally, we tested the cytotoxicity of gossypol against BRW in vivo, using
      the nude mouse xenograft model. Gossypol, given at a dose of 30 mg/kg per day
      five days a week for four weeks orally via gavage, was found to decrease the mean
      tumor weight of treated xenografts by more than 50% as compared to untreated
      xenografts. These findings suggest that gossypol has potential for further study
      as an agent for the treatment of primary CNS malignancies.

PMID- 7815103
TI  - Recording neurological impairment in clinical trials of glioma.
AB  - The criteria for clinical response to treatment in cerebral glioma remain poorly
      defined, but could be made more objective if simple measures of neurological
      impairments were included in the definitions. We assessed the utility of simple
      fast previously validated tests of limb impairment (Timed nine hole peg test and
      10 meter walk), memory (Williams delayed recall test) and language (Boston
      Aphasia Severity Rating Scale) in fifty patients with primary brain tumours to
      see if they could act as a surrogate for neurological impairment. The tests were
      compared with established measures of physical disability (Barthel Disability
      Index [BDI]) and handicap. Timed tests of hand function and gait were sensitive
      to minor impairments and were abnormal in patients with physical disability on
      BDI. Timed tests correlated well with handicap (rank correlation 0.734). Short
      term memory was impaired more commonly with tumours involving the left hemisphere
      (p < 0.01). Dysphasia limited testing of memory in 8%. Depression was associated
      with problems in limb function (p < 0.01), memory (p < 0.001), language (p <
      0.001), BDI (p < 0.001) and handicap (p < 0.001). The number of abnormal fast
      tests also correlated with the severity of handicap (rank correlation 0.786)
      indicating that memory impairment and aphasia contribute to handicap and should
      be assessed. Median time to complete all assessments was 7 minutes 20 seconds.
      Utilization of these simple tests will add sensitivity and objectivity to
      evaluation of neurological response in clinical trials and can be performed
      quickly by non medical staff.

PMID- 7815104
TI  - Enhancement of ACNU cytotoxicity by pretreatment with O6-methylguanine in ACNU
      resistant brain tumors.
AB  - O6-Methylguanine is a substrate of the DNA repair enzyme O6-methylguanine-DNA
      methyltransferase, which is involved in the repair mechanism of DNA damage
      induced by chloroethylnitrosoureas such as 1-(4-amino-2-methyl-5
      pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU). We
      tested the enhancement effect of O6-methylguanine pretreatment on ACNU
      cytotoxicity in ACNU-resistant brain tumors. Exposure to O6-methylguanine at
      various times ranging from 2 to 48 hours increased the cytotoxic effects of ACNU
      on C6-1 cells, and this effect was highest at higher concentrations 500 and 1,000
      microM. Colorimetric cytotoxicity assay revealed at least a two-fold increase in
      ACNU cytotoxicity relative to controls without O6-methylguanine. Intraarterial
      ACNU after treatment with O6-methylguanine (two intravenous bolus injections of
      80 and 40 mg/kg) significantly (P < 0.05 or P < 0.01) reduced the proliferation
      activity of transplanted C6-1 tumors for 96 hours after injection, whereas
      intravenous ACNU together with O6-methylguanine significantly (P < 0.05) reduced
      C6-1 activity for only 48 hours. Thus, pretreatment with O6-methylguanine
      prolonged the suppression effect of ACNU. The C6-1 tumors treated only with
      intravenous or intraarterial ACNU showed transient inhibition and rapid regrowth
      for 24 hours after treatment. These results indicate that O6-methylguanine
      increases ACNU cytotoxicity in an in vitro and in vivo brain tumor model.

PMID- 7815105
TI  - Risk factors for cerebral glioma in adults: a case-control study in an Italian
      population.
AB  - A case-control study on risk factors for cerebral tumors was conducted on an
      adult Italian population by the four Neurosurgical Departments of the Veneto
      Region, i.e. Padua, Treviso, Verona and Vicenza. The study recruited 195 cases of
      histologically-confirmed cerebral glioma. One hospital control was selected for
      each case. Cases and controls were matched for age, sex, data of hospitalization
      and residence. Information on both cases and controls was obtained from a
      relative. Uninvolved interviewers administered a structured questionnaire
      including items on the subject's education, occupation, lifestyle, medical
      history, exposure to radiation for diagnosis or therapy, head trauma and blood
      group and the medical history of family members. The series of cerebral tumors
      was first considered as an indistinct set: none of the risk factors examined
      showed a statistically significant association. A positive association was found
      with blood group A (OR = 6) when low-grade astrocytomas (n = 41) were considered
      separately. As for the malignant astrocytomas (n = 132), there was a suggestive
      but not statistically significant association with the presence of CNS tumors
      among first- and second-degree relatives (OR = 7.0). On the whole, this study
      yielded no clear and meaningful association for the various risk factors
      analyzed.

PMID- 7815106
TI  - A phase II study of intravenous carboplatin for the treatment of recurrent
      gliomas.
AB  - Thirty-two patients with recurrent glioma who had previously received radiation
      therapy and chemotherapy with nitrosoureas were treated with intravenous
      carboplatin every 3 weeks, starting at a dose of 350 mg/m2, with a dose
      escalation of 25 mg/m2 every 6 weeks until a level 4 hematologic toxicity was
      reached. Of the 28 patients who could be evaluated for a response, 50%
      demonstrated a response or had stabilization of their disease after two infusions
      of carboplatin. Their median time to tumor progression and median duration of
      survival were 19 weeks and 38 weeks. Thrombocytopenia was the major toxicity and
      was severe in one-third of the patients. No neurologic or renal toxicities were
      noted. Carboplatin has demonstrated activity against recurrent gliomas in
      patients who have already had extensive chemotherapy. Increasing the dose of
      carboplatin may improve the rate of response and the duration of progression-free
      survival in patients with recurrent glioma.

PMID- 7815107
TI  - Solitary cerebral metastasis from ovarian carcinoma: report of 4 cases.
AB  - Four cases of solitary cerebral metastasis from ovarian carcinoma are reported.
      Although systemic metastases from this type of tumor are frequent, they rarely
      affect the nervous system. From the 4 cases presented and a review of the
      literature, it appears that a better outcome may be obtained by a combined
      treatment of the cerebral metastasis, comprising surgery, radiotherapy and
      chemotherapy.

PMID- 7815109
TI  - 1st Congress of the European Association for Neuro-Oncology. October 15-18, 1994,
      Maastricht, The Netherlands. Abstracts.

PMID- 7815108
TI  - Metastatic epidural spinal cord compression: current concepts and treatment.
AB  - Metastatic epidural spinal cord compression (MESCC) is a medical emergency
      complicating the course of 5-10% of patients with cancer [1]. When diagnosis and
      treatment is early with the patient ambulatory prognosis for continued ambulation
      is good [2]. If the patient is nonambulatory or paraplegic, prognosis for
      meaningful recovery of motor and bladder function is markedly decreased. In the
      last decade, significant advances in the understanding, management and treatment
      of metastatic epidural spinal cord compression have occurred. Recent
      pathophysiological and pharmacological animals studies have afforded insights
      into disease mechanisms [3-9]. The audit of standard methods of investigation and
      magnetic resonance imaging have resulted in revision of guidelines for patient
      evaluation [10-17]. Finally, new surgical philosophies and technical advances
      have generated interest and controversy [18-25]. With improved clinical
      awareness, new imaging modalities will help us diagnose epidural spinal cord
      compression earlier and institute appropriate treatment.

PMID- 7815110
TI  - A critical appraisal of drainage in syringomyelia.
AB  - The use of drains in the treatment of syringomyelia has a simple and immediate
      appeal and has been practiced widely since the report of Abbe and Coley over 100
      years ago. Good short-term results have been claimed in the past, but long-term
      outcome is largely unknown. An experience in Birmingham, England is reviewed in
      which 73 patients who had had some form of syrinx drainage procedure performed
      were subsequently followed up. In these cases, a total of 56 syringopleural and
      14 syringosubarachnoid shunts had been inserted. Ten years after the operations,
      only 53.5% and 50% of the patients, respectively, continued to remain clinically
      stable. A 15.7% complication rate was recorded, including fatal hemorrhage,
      infection, and displacement of the drain from the pleural and syrinx cavities. At
      second operation or necropsy, at least 5% of shunts were discovered to be
      blocked. The effect of other drainage procedures that do not use artificial
      tubing, such as syringotomy and terminal ventriculostomy, was analyzed but found
      not to offer any substantial benefit. These results indicate that drainage
      procedures are not an effective solution to remedying the progressive,
      destructive nature of syringomyelia. It is suggested that, rather than attempting
      to drain the syrinx cavity, disabling the filling mechanism of the syrinx is more
      appropriate. Most forms of syringomyelia have a blockage at the level of the
      foramen magnum or in the subarachnoid space of the spine. Surgical measures that
      aim to reconstruct the continuity of the subarachnoid space at the site of the
      block are strongly recommended. Lowering the overall pressure of the
      cerebrospinal fluid is advocated when reestablishment of the pathways proves
      impossible. Syrinx drainage as an adjuvant to more physiological surgery may have
      a place in the treatment of syringomyelia. If two procedures are done at the same
      time, however, it is difficult to ascribe with certainty a success or failure,
      and it is suggested that the drainage procedure be reserved for a later attempt
      if the elective first operation fails.

PMID- 7815111
TI  - Crossed-screw fixation of the unstable thoracic and lumbar spine.
AB  - An ideal spinal construct should immobilize only the unstable spinal segments,
      and thus only the segments fused. Pedicle fixation techniques have provided
      operative stabilization with the instrumentation of a minimal number of spinal
      segments; however, some failures have been observed with pedicle instrumentation.
      These failures are primarily related to excessive preload forces and limitations
      caused by the size and orientation of the pedicles. To circumvent these problems,
      a new technique, the crossed-screw fixation method, was developed and is
      described in this report. This technique facilitates short-segment spinal
      fixation and uses a lateral extracavitary approach, which provides generous
      exposure for spinal decompression and interbody fusion. The technique employs two
      large transverse vertebral body screws (6.5 to 8.5 mm in diameter) to bear axial
      loads, and two unilateral pedicle screws (placed on the side of the exposure) to
      restrict flexion and extension deformation around the transverse screws and to
      provide three-dimensional deformity correction. The horizontal vertebral body and
      the pedicle screws are connected to rods and then to each other via rigid
      crosslinking. The transverse vertebral body screws are unloaded during insertion
      by placing the construct in a compression mode after the interbody bone graft is
      placed, thus optimizing the advantage gained by the significant "toe-in"
      configuration provided and further decreasing the chance for instrumentation
      failure. The initial results of this technique are reported in a series of 10
      consecutively treated patients, in whom correction of the deformity was
      facilitated. Follow-up examination (average 10.1 months after surgery)
      demonstrated negligible angulation. Chronic pain was minimal. The crossed-screw
      fixation technique is biomechanically sound and offers a rapid and safe form of
      short-segment three-dimensional deformity correction and solid fixation when
      utilized in conjunction with the lateral extracavitary approach to the unstable
      thoracic and lumbar spine. This approach also facilitates the secure placement of
      an interbody bone graft.

PMID- 7815112
TI  - Congenital cystic supratentorial hemangioblastoma. Case report.
AB  - The first documented case of congenital supratentorial hemangioblastoma is
      presented, occurring in a 3-week-old infant. Extensive review of the literature
      revealed approximately 83 cases of supratentorial hemangioblastoma; however, only
      one of these occurred in the first year of life, and that case was not presented
      in detail.

PMID- 7815113
TI  - Delayed occurrence of cerebellar pleomorphic xanthoastrocytoma after
      supratentorial pleomorphic xanthoastrocytoma removal. Case report.
AB  - The authors report the case of a 36-year-old woman who underwent gross total
      resection of a right cerebellar pleomorphic xanthoastrocytoma with atypical
      features. She had undergone surgery 16 years previously for what was thought to
      be a right frontal glioblastoma multiforme. In retrospect, based on the
      histopathology and the clinical course, both lesions were considered to represent
      atypical variants of pleomorphic xanthoastrocytoma. This report examines the
      histological and clinical characteristics of this posterior fossa lesion, which
      exhibited histologically malignant features but has run a relatively indolent
      course.

PMID- 7815114
TI  - Desmoplastic fibroma of the skull. Case report.
AB  - Desmoplastic fibroma is a rare benign neoplasm of bone; only three cases have
      been reported involving the skull. The radiographic and histological aspects of a
      case of desmoplastic fibroma involving the parietal bone are reported.

PMID- 7815115
TI  - Malignant intraventricular schwannoma. Case report.
AB  - The authors present the clinical, radiological, and pathological features of a
      malignant schwannoma occurring in the right lateral ventricle of a 40-year-old
      man. Metastasis to both cerebellopontine angles and to the cerebellum was found 7
      months after subtotal removal of the tumor.

PMID- 7815116
TI  - Spinal cord compression due to Masson's vegetant intravascular
      hemangioendothelioma. Case report.

PMID- 7815117
TI  - Primary mycotic abscess of the brain caused by Fonsecaea pedrosoi. Case report.
AB  - A case of cerebral abscess caused by Fonsecaea pedrosoi is reported in a
      nonimmunocompromised 15-year-old boy. In the absence of a primary cutaneous
      lesion, this fungus was considered to be a primary neuropathogen. The fungus was
      cultured and characterized from the abscess material obtained at surgery. Prompt
      therapy using amphotericin B and 5-flucytosine helped in the successful recovery
      of this patient.

PMID- 7815118
TI  - Herniation of the spinal cord. Case report.
AB  - Herniation of the spinal cord, or displacement of the cord outside the dura, is
      so rare that only 13 cases have been reported in the literature. The authors
      report a new case of spontaneous herniation of the spinal cord in a 38-year-old
      man who presented with lower left limb paresis and Brown-Sequard syndrome, with a
      T-8 sensory level. Displacement of the spinal cord was noted on computerized
      tomography following myelography and on magnetic resonance imaging. The herniated
      cord was confirmed at operation and reduced intradurally. Postoperatively, the
      patient showed complete neurological recovery. Based on a review of the
      literature, herniation of the spinal cord may be classified as spontaneous,
      iatrogenic, or traumatic. At cervical levels, the spinal cord has herniated into
      an iatrogenic pseudomeningocele located dorsally. At thoracic levels, spinal cord
      herniations were reported to be in a preexisting extradural arachnoid cyst
      located ventrally. The authors propose a pathogenesis for spinal cord herniation
      based on abnormal positioning of the spinal cord in the dural sleeve and the
      known anteroposterior movements of the cord that occur with cardiac and
      respiratory pulsations. The presence of a dural defect situated on the concavity
      of the spinal curvature is a prerequisite for this rare condition. As adhesions
      develop between the cord and the edges of the dural defect, cerebrospinal fluid
      pulsations push the cord into a preexisting cyst. The authors suggest modifying
      the classification by Nabors, et al., of spinal meningeal cysts to include this
      mechanism of spinal cord herniation. This diagnosis should also be considered in
      the differential diagnosis of myelopathy in the absence of a mass lesion.

PMID- 7815119
TI  - Treatment of vertebral artery dissecting aneurysm by aneurysm trapping and
      posterior inferior cerebellar artery reimplantation. Case report.
AB  - The author presents the case of a patient with a ruptured vertebral artery
      dissecting aneurysm in which the posterior inferior cerebellar artery (PICA)
      arose from the wall of the aneurysm. The aneurysm was treated by trapping and the
      PICA was anastomosed to the vertebral artery proximal to the dissection. This
      technique allows intraoperative obliteration of the aneurysm while maintaining
      normal blood flow to the PICA.

PMID- 7815120
TI  - Accurate placement of the atrial catheter in ventriculoatrial shunts. Technical
      note.
AB  - A combined radiological and surgical technique that permits identification of
      appropriate recipient vessels and accurate placement of the atrial catheter in
      ventriculoatrial shunts is described. The procedure uses readily available
      radiological skills and reduces operation time and morbidity related to
      malpositioning of the distal catheter.

PMID- 7815121
TI  - Surgery and vasospasm.

PMID- 7815122
TI  - Treatment of intrathecal morphine overdose.

PMID- 7815123
TI  - Extracerebral fluid collection in infancy.

PMID- 7815124
TI  - Computerized tomography-guided biopsy.

PMID- 7815125
TI  - Split-calvaria osteoplastic flap.

PMID- 7815126
TI  - No sweat and a false view.

PMID- 7815127
TI  - Neurofibromatosis and multicentric gliomas.

PMID- 7815128
TI  - Cervical cord tethering.

PMID- 7815129
TI  - Aggressive meningeal tumors: review of a series.
AB  - A series of 25 patients with aggressive meningeal tumors was studied to determine
      the efficacy of various management options. The median age of the patients was 52
      years, with a range of 13 to 73 years. A marked male preponderance (64%) was
      noted. Twenty of 25 patients experienced recurrence during a median follow-up
      time of 47 months. Survival and freedom from recurrence varied with histological
      diagnosis. Recurrence was noted sooner in patients who had received partial
      resections on first presentation of tumor than in those who had received total
      resections at first presentation. Survival time was also shorter for patients who
      underwent partial resections at first presentation than for patients who
      underwent total resections. Patients' prognoses did not improve as a result of
      either chemotherapy or radiotherapy. Of six patients with extracranial
      metastases, the median time to metastasis was 102 months, with a 5-year
      metastasis-free rate of 85%. The most common sites of metastasis in these six
      patients were lung and bone. In each tumor type, histological features used in
      diagnosis and radiological features studied from computerized tomography and
      magnetic resonance imaging were evaluated, compared, and discussed. Of eight
      patients studied with an in vivo bromodeoxyuridine (BUdR) labeling index (LI),
      seven showed an LI of 1% or more. The authors support the incorporation of the
      BUdR LI into the diagnostic process to provide a better estimate of the potential
      for tumor recurrence.

PMID- 7815130
TI  - Dorsal root entry zone lesions for intractable pain after trauma to the conus
      medullaris and cauda equina.
AB  - This review was undertaken to determine the efficacy of using dorsal root entry
      zone (DREZ) lesions to treat intractable pain caused by trauma to the conus
      medullaris and cauda equina. Traumatic lesions of this area are unique in that
      both the spinal cord and the peripheral nerve roots are injured. Although DREZ
      lesions have been shown to relieve pain of spinal cord origin in many patients,
      they have been shown not to relieve pain of peripheral nerve origin. Therefore,
      39 patients with trauma to the conus medullaris and cauda equina who underwent
      DREZ lesioning for intractable pain were reviewed retrospectively. The results of
      this review demonstrate the efficacy of DREZ lesions in these patients. At a mean
      follow-up period of 3.0 years, 54% of patients were pain-free without
      medications, and 20% required only nonnarcotic analgesic drugs for pain that no
      longer interfered with their daily activities. Better outcomes were noted in
      patients with an incomplete neurological deficit, with pain having an
      "electrical" character, and with injuries due to blunt trauma. Operative
      complications included weakness (four patients), bladder or sexual dysfunction
      (three), cerebrospinal fluid leak (two), and wound infection (two), but overall,
      79.5% of patients (31 of 39) were without serious complications. Complications
      were limited to patients with prior tissue damage at the surgical exploration
      site and were most prevalent in patients who underwent bilateral DREZ lesions. In
      conclusion, this preliminary report suggests that DREZ lesions may be useful in
      combating intractable pain from traumatic injuries to the conus medullaris and
      cauda equina, with some risk to neurological function that may be acceptable in
      this group of patients.

PMID- 7815131
TI  - Spinal cord stimulation in the treatment of paraplegic pain.
AB  - Twenty-five patients suffering from intractable pain due to a chronic spinal cord
      lesion underwent a percutaneous test of spinal cord stimulation. At the end of
      the test period, 40.9% of the patients reported a mean of 65% pain relief and
      these patients were selected for ongoing stimulation. At a mean follow-up time of
      37.2 months the success rate, based on the number of patients with more than 50%
      pain relief, had fallen to 18.2%. Pain relief rates were analyzed in relation to
      quality of pain, neurological status, level and extent of the lesion, and
      electrode level to identify prognostic factors that could improve the clinical
      usefulness of spinal cord stimulation. Patients experiencing painful spasms or a
      constrictive type of pain and with incomplete thoracic lesions were found to be
      the best candidates for spinal cord stimulation.

PMID- 7815132
TI  - Wound healing in trophic ulcers in spina bifida patients.
AB  - Eight cases of tethered conus medullaris with trophic ulcers in the foot in spina
      bifida patients are presented. The ulcers, which had remained unhealed for 1 to 8
      years prior to surgery, healed in a few weeks after the tethered conus was
      released. The possibility of some neurotrophic factor in wound healing is
      suggested.

PMID- 7815133
TI  - Timing of postoperative intracranial hematoma development and implications for
      the best use of neurosurgical intensive care.
AB  - This study records the incidence and timing of postoperative hematomas in
      neurosurgical patients and analyzes the best use of neurosurgical intensive care.
      In 2305 patients undergoing freehand or stereotactic biopsy, elective or
      emergency craniotomy, or posterior fossa surgery, 50 (2.2%) developed a hematoma.
      Clinical deterioration as a result of postoperative hematoma occurred within 6
      hours of surgery in 44 patients and more than 24 hours after surgery in six
      patients. Although patients undergoing posterior fossa surgery or emergency
      craniotomy warrant longer periods of intensive-care observation, patients having
      elective supratentorial operations can safely be transferred to a neurosurgical
      ward for observation, provided they have regained their preoperative neurological
      status by 6 hours postsurgery.

PMID- 7815134
TI  - Hemihypoglossal-facial nerve anastomosis in treating unilateral facial palsy
      after acoustic neurinoma resection.
AB  - Eight patients underwent hemihypoglossal-facial nerve anastomosis (anastomosis of
      a split hypoglossal nerve to the facial nerve) for treatment of unilateral facial
      palsy. All patients previously had undergone resection of a large acoustic
      neurinoma and the facial nerve had been resected at that time. The interval
      between tumor resection and hemihypoglossal-facial nerve anastomosis ranged from
      1 to 6 months, with an average of 2.1 months. Postoperative recovery of facial
      movement was good in all cases during an average follow-up period of 4.2 years.
      In all eight patients, the degree of hypoglossal nerve atrophy on the operated
      side was graded mild or moderate, but not severe. It was concluded that
      hemihypoglossal-facial nerve anastomosis results in good facial reanimation as
      long as the procedure is performed early after the onset of facial palsy and that
      this procedure may reduce the degree of hemiglossal atrophy in comparison with
      classic hypoglossal-facial nerve anastomosis.

PMID- 7815135
TI  - Endothelin concentrations in patients with aneurysmal subarachnoid hemorrhage.
      Correlation with cerebral vasospasm, delayed ischemic neurological deficits, and
      volume of hematoma.
AB  - Plasma and cerebrospinal fluid (CSF) concentrations of endothelin (ET)-1, ET-3,
      and big ET-1 in patients with aneurysmal rupture were measured serially for 2
      weeks after the onset of aneurysmal subarachnoid hemorrhage (SAH) and compared
      with levels of ETs in patients without SAH and the plasma concentrations of ETs
      in normal volunteers. Big ET-1 was the predominant peptide present in the CSF of
      SAH patients. The CSF concentrations of big ET-1, ET-1, and ET-3 were
      significantly higher in older patients than in younger patients. In SAH patients
      with cerebral vasospasm (CVS) documented by transcranial Doppler sonography and
      clinical signs, postoperative concentrations of ETs in the CSF remained at or
      were increased above levels measured before surgery. In SAH patients without CVS,
      the concentrations of ETs in the CSF decreased with time, whereas the time course
      of CVS coincided with the increase in concentrations of big ET-1 and ET-1. The
      temporal dependence of concentrations of big ET-1 and ET-1 in SAH patients with
      and without CVS were significantly different. The volume of hematoma in the basal
      cisterns as detected by computerized tomography was predictive of the
      concentrations of ETs in the CSF. Plasma concentrations of ETs were not
      correlated with CVS. The possible role of ETs in the pathogenesis of CVS
      associated with SAH and the controversial data reported to date are discussed.

PMID- 7815136
TI  - Transmaxillosphenoidal approach to tumors invading the medial compartment of the
      cavernous sinus.
AB  - A transmaxillosphenoidal approach was used to remove sellar tumors invading the
      cavernous sinus. This procedure, a widening of the standard transsphenoidal
      approach to the sella turcica, uses the sublabial or transnasal route in which
      the medial wall of the maxillary sinus is laterally dislocated. This method
      provides good exposure of the prominences of bone above the carotid artery which
      lies on the posterolateral wall of the sphenoid sinus. This bone area is the key
      to opening the cavernous sinus inferomedially and removing lesions within its
      medial compartment. The inferomedial approach takes an entirely extracerebral
      route so that tumors invading the cavernous sinus through its medial wall are
      approached inferomedially following the direction of tumor growth. It also allows
      direct visualization of the intracavernous carotid artery during tumor removal,
      thus sparing the cranial nerves, which run on the opposite side. Adequate
      surgical exposure of a pituitary adenoma is achieved with a custom-made
      sphenoidal retractor with asymmetric blades, the shorter blade holding aside the
      thin medial wall of the maxillary sinus. Between October, 1989, and July, 1993,
      11 patients with tumors invading the cavernous sinus underwent surgery via this
      approach; 10 had pituitary adenomas and one had a craniopharyngioma. Eight tumors
      were treated by primary operation: four tumors were totally and four subtotally
      (> 80%) removed; one tumor already operated on elsewhere was totally removed; and
      of two tumors already operated on and irradiated, one was subtotally removed and
      the other only partially (approximately 40%) removed owing to marked
      postirradiation scarring. None of the patients suffered permanent cranial nerve
      deficit and all but one showed marked clinical improvement.

PMID- 7815137
TI  - Adenovirally mediated gene transfer into experimental solid brain tumors and
      leptomeningeal cancer cells.
AB  - Among the appealing features of adenoviruses as vectors for transfer of genes
      into the central nervous system (CNS) are that they are not neurotoxic, they can
      accommodate the insertion of several large genes, they are not associated with
      the hazards of insertional mutagenesis, and they can be concentrated to a high
      titer preparation. The authors evaluated the feasibility of using adenovirally
      mediated gene transfer into cultured human glioma cells and in rat models of
      solid brain tumors and meningeal cancer. Replication-deficient adenoviral vector
      particles carrying a nuclear-localizing lacZ gene were injected into established
      9L cerebral gliomas in Fischer rats. In addition, the adenoviral vector was
      injected into the subarachnoid space, either simultaneously with intrathecal
      tumor inoculation or after establishing leptomeningeal cancer. The brains and
      spinal cords were removed at various intervals for histochemical evaluation for
      beta-galactosidase activity using X-Gal staining. Additional rats received a
      stereotactic intracerebral injection of the vector into normal brain. No clinical
      abnormalities were observed in the injected rats. Injection of the adenoviral
      vector into normal brain resulted in diffuse transduction of astrocytes,
      microglia, neurons, and endothelial cells at the injection site. Injection of a
      high-concentration vector preparation into cerebral gliomas resulted in effective
      tumor transduction. Intrathecal injection of the vector in rats with meningeal
      cancer resulted in transduction of the infiltrating tumor in the subarachnoid
      space when injections were given simultaneously with, or 7 days after, tumor
      inoculation. Transduction rates of both solid and leptomeningeal tumors
      correlated with the number of injected particles. These results suggest that
      adenoviral vectors can efficiently transduce solid brain tumors and that the
      vectors survive in the cerebrospinal fluid for a sufficient period of time to
      allow leptomeningeal tumor transduction. Adenoviral vector should be evaluated
      for its potential use in therapeutic gene transfer approaches in malignancies of
      the CNS.

PMID- 7815138
TI  - Primary peripheral-postthymic T-cell lymphoma in the central nervous system:
      immunological and molecular approaches to diagnosis.
AB  - Primary intracranial T-cell lymphoma is a very rare clinical entity, and only
      limited biological studies of this disease have been undertaken. A tumor specimen
      from a patient with a primary leptomeningeal and perivascular presentation of a T
      cell lymphoma was analyzed using cellular and molecular techniques. Frozen
      sections of the sample were examined by immunohistochemical techniques using
      monoclonal antibodies to phenotypic marker antigens expressed on human lymphoid
      cells. Intercellular adhesion molecules expressed on the tumor were studied, as
      was expression of messenger ribonucleic acid (mRNA) transcripts of the T-cell
      receptor variable alpha and beta chain genes. The immunophenotypical analysis of
      lymphoma revealed that the tumor expressed CD2, CD3, CD4, CD5, CD25 and HLA-DR.
      In addition, all of the adhesion molecules studied (ICAM-1, LFA-3, VLA-1, CD11a,
      CD11b, and CD11c) were detected on the cell surface. Polymerase chain reaction
      amplification of mRNA from the tumor demonstrated 10 V alpha and three V beta T
      cell receptor subfamilies, indicating that this tumor was a low-grade well
      differentiated helper type of peripheral T-cell lymphoma of the central nervous
      system. In addition, the tumor was derived from multiple T-cell lineages.

PMID- 7815139
TI  - Transfection with bFGF sense and antisense cDNA resulting in modification of
      malignant glioma growth.
AB  - Aberrant autocrine control by peptide growth factors is a possible mechanism by
      which disordered regulation of cell proliferation may occur. The authors used the
      C6 glioma cell line as a model to study the role of basic fibroblast growth
      factor (bFGF) in tumor growth by transfection with bFGF complementary
      deoxyribonucleic acid in both the sense and antisense orientation. Clones with
      high messenger ribonucleic acid expression of the sense construct have increased
      proliferation in cell culture and increased levels of intracellular and
      extracellular bFGF. Clones with high expression of the antisense construct show
      decreased proliferation in culture and reduced levels of immunologically
      detectable bFGF.

PMID- 7815140
TI  - Characteristics of relaxation induced by calcitonin gene-related peptide in
      contracted rabbit basilar artery.
AB  - Increasing evidence suggests that disturbances in the modulatory influence of the
      vasoactive peptide, calcitonin gene-related peptide (CGRP), contribute to the
      pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH). However,
      only limited success has been achieved in trials attempting to ameliorate
      vasospasm by modifying CGRP function. To better understand the potential utility
      of targeting CGRP-mediated relaxation, it is important both to identify the
      interactions CGRP may have with other elements of the vasospastic response and to
      characterize the mechanisms through which CGRP elicits vasodilative effects. The
      present studies examined the effects of CGRP on vascular responsiveness using
      tension measurements of ring strips of rabbit basilar artery maintained in vitro.
      Pretreatment of vessels with CGRP (100 nM) inhibited vasoconstrictor responses to
      the potent protein kinase C (PKC) activator, phorbol 12,13-dibutyrate (PDB). This
      particular contractile response was selected because PKC-mediated
      vasoconstriction is a critical component of the vasospastic response after SAH.
      In a posttreatment paradigm, CGRP was also found to reverse established
      constriction responses to PDB (2 nM) and histamine (3 microM) in a dose-dependent
      manner. When tested against the maximum effective dose of PDB (30 nM) in the
      posttreatment paradigm, CGRP (100 nM) did not elicit significant relaxation.
      However, after washing both of these drugs out of the test chamber, a persistent
      effect of CGRP was revealed: the decay of PDB-induced contraction was accelerated
      in vessels that had previously been treated with CGRP. These findings indicate
      that CGRP elicits both immediate and sustained influences on contractile
      responses mediated by PKC. Finally, two potential mechanisms for the vascular
      response to CGRP were examined. Adenosine triphosphate (ATP)-sensitive K+
      channels do not appear to participate in CGRP-mediated dilation; inhibitors of
      these channels, glibenclamide and tolbutamide, did not block CGRP-induced
      relaxation. In contrast, a possible role for the nucleotide cyclic adenosine
      monophosphate (cAMP) in the vascular response to CGRP was indicated by the dose
      dependent elevation of cAMP levels by CGRP. Together these studies indicate that
      CGRP can modulate the contractile response to PKC activation. These effects are
      associated with increases in the levels of cAMP, but occur independently of
      fluxes through ATP-sensitive K+ channels.

PMID- 7815141
TI  - Microvascular anatomy of the anterior surface of the medulla oblongata and olive.
AB  - The arterial supply and the microanatomy of the anterior surface of the medulla
      oblongata and olive were studied in 11 cadaveric specimens, with investigation of
      the size, course, and length of the arteries. Two distinct anatomical entities
      divide the vascular supply in this region: 1) the pyramid, which is the anterior
      surface of the medulla; and 2) the olive, which is adjacent to the lateral aspect
      of the pyramid. Primary vascularization of the pyramid was via small branches of
      the anterior spinal artery, a branch of the vertebral artery. Minute perforators
      from the anterior spinal artery were found in all specimens. Arterial supply to
      the olive varied by location: its anterior aspect was primarily supplied by the
      anterior spinal artery; the upper portion of the posterior aspect of the olive
      was supplied by the vertebral artery, the anterior inferior cerebellar artery,
      and the basilar artery; and the middle and lower portions of the posterior aspect
      were fed by the vertebral artery and posterior inferior cerebellar artery. These
      arteries supplied the medulla through the small branches directed toward the
      olive. The authors observed a wide anastomotic net connecting the small arteries
      in this area. These patterns of microvascular supply of the pyramid and olive may
      deepen the understanding of clinical and pathological conditions resulting from
      arterial occlusion. The existence of an anastomotic net may account for the rare
      incidence of medullary infarction in the olive region.

PMID- 7815142
TI  - Combined sagittal and lateral sinus dural fistulae occlusion.
AB  - The clinical course of three patients who had combined sagittal and lateral sinus
      dural fistulae is described. One patient, with impending blindness and a short
      life span, underwent right lateral sinus thrombosis in one stage. The second
      patient underwent sagittal and right lateral sinus thrombosis in four stages, and
      her remaining lateral sinus spontaneously occluded. A small untreated fistula
      persists in the right lower sigmoid. The third patient underwent sagittal sinus,
      left lateral sinus, and left parietal sinus thrombosis in six stages. A small
      untreated far-anterior fistula persists. All "satellite" fistulae have
      spontaneously disappeared. The small asymptomatic untreated residual fistulae
      have no demonstrable retrograde venous drainage and, therefore, require no
      treatment at this time.

PMID- 7815143
TI  - A proposed classification for spinal and cranial dural arteriovenous fistulous
      malformations and implications for treatment.
AB  - A classification is proposed that unifies and organizes spinal and cranial dural
      arteriovenous fistulous malformations (AVFMs) into three types based upon their
      anatomical similarities. Type I dural AVFMs drain directly into dural venous
      sinuses or meningeal veins. Type II malformations drain into dural sinuses or
      meningeal veins but also have retrograde drainage into subarachnoid veins. Type
      III malformations drain into subarachnoid veins and do not have dural sinus or
      meningeal venous drainage. The arterial supply in each of these three types is
      derived from meningeal arteries. The anatomical basis of the proposed
      classification is presented with several cases that illustrate the three types of
      dural AVFMs. A rationale for the treatment of spinal and cranial dural AVFMs
      according to their anatomical characteristics is discussed.

PMID- 7815144
TI  - Linear accelerator radiosurgery for arteriovenous malformations: the relationship
      of size to outcome.
AB  - Between May, 1988 and August, 1993, 158 patients with arteriovenous malformations
      (AVMs) were treated radiosurgically at the University of Florida. A mean dose of
      1560 cGy was directed to the periphery of the lesions, which had a mean volume of
      9 cc (0.5 to 45.3 cc). One hundred thirty-nine of these individuals were treated
      with one isocenter. The mean follow-up interval was 33 months with clinical
      information available on 153 of these patients. Patients were followed until
      magnetic resonance (MR) studies suggested complete AVM thrombosis. An arteriogram
      was then performed, if possible, to verify occlusion status. If arteriography
      revealed any persistent nidus at 36 months posttreatment, the residual nidus was
      re-treated. Outcome categories of AVMs analyzed included the following
      possibilities: 1) angiographic cure; 2) angiographic failure; 3) re-treatment; 4)
      MR image suggested cure; 5) MR image suggested failure; 6) patient refused follow
      up evaluation; 7) patient lost to follow-up study; or 8) patient deceased. The
      endpoints for success or failure of radiosurgery were as follows: angiographic
      occlusion (success), re-treatment (failure), and death due to AVM hemorrhage
      (failure). Fifty-six patients in this series reached one of the endpoints.
      Successful endpoints were seen in 91% of AVMs between 1 and 4 cc in volume, 100%
      of AVMs 4 to 10 cc in volume, and 79% of AVMs greater than 10 cc in volume. The
      more traditional measure of radiosurgical success, percentage of angiograms
      showing complete obliteration, was obtained in 81% of AVMs between 1 and 4 cc in
      volume, 89% of AVMs between 4 and 10 cc in volume, and 69% of AVMs greater than
      10 cc in volume. A detailed analysis of the relationship of all outcome
      categories to size is presented.

PMID- 7815145
TI  - Deep central arteriovenous malformations of the brain: the role of endovascular
      treatment.
AB  - Cerebral deep central arteriovenous malformations (AVMs) are uncommon lesions
      associated with considerable difficulty in treatment. The authors report a series
      of 14 deep central AVMs treated by endovascular methods and examine the present
      role of endovascular treatment. This treatment used alone resulted in complete
      obliteration of AVMs in approximately 15% of case and reduction in 50% to a size
      permitting treatment by means of radiosurgery. Reversal of previous neurological
      signs and symptoms occurred in 35.7% of embolized patients. Overall, nearly 80%
      of patients had either complete obliteration of the lesion, reduction to a size
      allowing radiosurgical treatment, or reversal of previous neurological deficits.
      There were treatment complications in 14.3% of the cases. Endovascular treatment
      methods may make a significant contribution to the therapy of AVMs that have a
      particularly poor course and are difficult to treat by other means.

PMID- 7815146
TI  - Surgical interruption of intradural draining vein as curative treatment of spinal
      dural arteriovenous fistulas.
AB  - To establish if interruption of the intradural draining spinal vein or surgical
      excision are curative treatments for spinal dural arteriovenous fistulas (AVFs),
      the medical records and radiographic studies of 19 patients with spinal dural
      AVFs and progressive myelopathy were reviewed. Spinal arteriograms were obtained
      before and within 2 weeks after surgery in 19 patients, and after a delay of 4
      months or more in 11 patients. The mean clinical and arteriographic follow up was
      at 37 and 35 months, respectively. In the 11 patients who underwent excision of
      the dural AVF there was no evidence of a residual lesion upon immediate or
      delayed postoperative arteriography. Surgery in eight patients consisted of
      simple interruption of the intradural draining vein as it entered the
      subarachnoid space. In six of these patients the vein draining the AVF
      intrathecally provided the only venous drainage of the AVF. In these six patients
      there was no immediate (six of six) or delayed (four of six) arteriographic
      evidence of residual or recurrent flow through the AVF. Two patients had an AVF
      with both intra- and extradural venous drainage; after intradural division of the
      draining vein there was residual flow through the AVF into the extradural venous
      system. In one of these two patients intrathecal venous drainage was
      reestablished, which required additional therapy. In the other patient the
      extradural AVF spontaneously thrombosed and was not evident on delayed follow-up
      arteriography. In patients with spinal dural AVFs with only intrathecal medullary
      venous drainage, which includes most patients with these lesions, surgical
      interruption of the intradural draining vein provides lasting and curative
      treatment. In patients with both intra- and extradural drainage of the AVF,
      complete excision of the fistula or interruption of the intra- and extradural
      venous drainage of the fistula is indicated. In patients in whom a common vessel
      supplies the spinal cord and the dural AVF, simple surgical interruption of the
      vein draining the AVF is the treatment of choice, as it provides lasting
      obliteration of the fistula and it is the only treatment that does not risk
      arterial occlusion and cord infarction. Simple interruption of the venous
      drainage of a spinal dural AVF provides lasting occlusion of the fistula, as it
      does for cranial dural AVFs, if all pathways of venous drainage are interrupted.
      This result provides further evidence that the venous approach to the treatment
      of dural AVFs can be used successfully.

PMID- 7815147
TI  - Microvascular decompression for hemifacial spasm.
AB  - The authors report the results of 782 microvascular decompression procedures for
      hemifacial spasm in 703 patients (705 sides), with follow-up study from 1 to 20
      years (mean 8 years). Of 648 patients who had not undergone prior intracranial
      procedures for hemifacial spasm, 65% were women; their mean age was 52 years, and
      the mean preoperative duration of symptoms was 7 years. The onset of symptoms was
      typical in 92% and atypical in 8%. An additional 57 patients who had undergone
      prior microvascular decompression elsewhere were analyzed as a separate group.
      Patients were followed prospectively with annual questionnaires. Kaplan-Meier
      methods showed that among patients without prior microvascular decompression
      elsewhere, 84% had excellent results and 7% had partial success 10 years
      postoperatively. Subgroup analyses (Cox proportional hazards model) showed that
      men had better results than women, and patients with typical onset of symptoms
      had better results than those with atypical onset. Nearly all failures occurred
      within 24 months of operation; 9% of patients underwent reoperation for recurrent
      symptoms. Second microvascular decompression procedures were less successful,
      whether the first procedure was performed at Presbyterian-University Hospital or
      elsewhere, unless the procedure was performed within 30 days after the first
      microvascular decompression. Patient age, side and preoperative duration of
      symptoms, history of Bell's palsy, preoperative presence of facial weakness or
      synkinesis, and implant material used had no influence on postoperative results.
      Complications after the first microvascular decompression for hemifacial spasm
      included ipsilateral deaf ear in 2.6% and ipsilateral permanent, severe facial
      weakness in 0.9% of patients. Complications were more frequent in reoperated
      patients. In all, one operative death (0.1%) and two brainstem infarctions (0.3%)
      occurred. Microvascular decompression is a safe and definitive treatment for
      hemifacial spasm with proven long-term efficacy.

PMID- 7815148
TI  - Quantified patterns of mossy fiber sprouting and neuron densities in hippocampal
      and lesional seizures.
AB  - Quantified hippocampal mossy fiber synaptic reorganization and neuron losses were
      measured to determine the pathological features associated with epileptogenic
      fascia dentata. Twenty-five patients with temporal lobe epilepsy (TLE) were
      classified as having either mesial temporal sclerosis (MTS; 16 patients), with
      seizure genesis in the hippocampus, or temporal mass lesions (nine patients),
      with seizures that were probably extrahippocampal. Neo-Timm's histochemistry
      identified mossy fiber sprouting, and aberrant fascia dentata puncta densities
      were objectively measured by light microscopic analysis on an image-analysis
      computer. neuron densities determined cell losses and the two seizure groups were
      compared to control specimens obtained from autopsies. Results showed
      significantly greater fascia dentata mossy fiber puncta densities and neuron
      losses in TLE patients compared to autopsy specimens (p < 0.026). Furthermore,
      there were significant differences between the two seizure groups: 1) mossy fiber
      puncta densities in the inner molecular layer were significantly greater in MTS
      compared to lesions (p < 0.02), and 2) mossy fiber puncta densities were greater
      in the inner molecular layer than in the stratum granulosum in 14 of 16 MTS
      patients (88%) compared to four of nine patients with lesions (44%, p < 0.01).
      Neuron densities were significantly different comparing MTS, lesion and control
      groups for stratum granulosum (p = 0.0001) and Ammon's horn (p = 0.0001), with
      each group significantly different (p < 0.05) compared to another. All patients
      were either seizure-free or significantly improved 1 year or more after en bloc
      temporal lobectomy. There were no significant correlations between fascia dentata
      mossy fiber puncta densities and counts of hilar neurons, CA4 pyramids, granule
      cells, or years of seizures. This indicates that inner molecular layer mossy
      fiber puncta densities and neuron losses are greater in patients with MTS than in
      those with lesions, and mossy fiber sprouting probably contributes to the
      pathophysiology of hippocampal seizures. Furthermore, these data show that some
      patients with extrahippocampal lesions have mossy fiber sprouting similar to MTS
      patients, suggesting that hippocampi in lesion patients may be capable of
      epileptogenesis from synaptic reorganization.

PMID- 7815149
TI  - Influence of the type of initial precipitating injury and at what age it occurs
      on course and outcome in patients with temporal lobe seizures.
AB  - The type of initial precipitating injury and the age at which it occurred in 20
      patients with nonlesional temporal lobe epilepsy (TLE) were related to clinical
      features, presurgical neuroimaging, quantified hippocampal pathologies, and
      seizure outcomes. Clinical data, neuroimaging records, and seizure outcomes were
      abstracted from medical records and confirmed with patient and family contacts.
      Hippocampal neuron losses and mossy fiber reactive synaptogenesis were quantified
      independently. Results showed that the type of initial precipitating injury and
      the patient's age at which it occurred were related to the clinicopathological
      features of TLE. An initial precipitating injury occurred in 18 patients (90%),
      all of whom had mesial temporal sclerosis (MTS). Patients with a prolonged
      initial seizure or a nonseizure initial precipitating injury before age 5 years
      were significantly more likely to have unilateral hippocampal atrophy (p < 0.05)
      shown on magnetic resonance (MR) imaging, and had significantly greater inner
      molecular layer mossy fiber puncta densities (p < 0.001) than patients with
      nonprolonged childhood initial precipitating injuries and/or seizures after age 5
      years. Furthermore, nonseizure injuries in patients before age 5 years had
      significantly longer latent periods (p < 0.05), and the patients did not respond
      to surgical treatment as well as other MTS patients. Those with an initial
      precipitating injury after age 5 years had MTS but showed significantly less
      inner molecular layer mossy fiber sprouting (p < 0.05) than patients whose
      injuries appeared before age 5 years. Patients without an initial precipitating
      injury (idiopathic TLE) had significantly fewer neuron losses (p < 0.05) and
      inner molecular layer mossy fiber puncta densities (p < 0.05) and had worse
      outcomes following en bloc temporal lobectomy compared to patients with MTS who
      had experienced initial precipitating injuries. Patients with unilateral
      hippocampal abnormalities on MR imaging did not show significant differences in
      neuron losses or aberrant mossy fiber puncta densities compared to patients
      without asymmetry. These results support the hypothesis that the type of initial
      precipitating injury and the age at which the injury occurred initiates and
      influences the pathophysiological process that eventually develops into MTS.
      These data support the notion that the pathophysiology of hippocampal damage and
      mossy fiber sprouting after an initial precipitating injury may be a progressive
      process.

PMID- 7815150
TI  - Unilateral hippocampal mossy fiber sprouting and bilateral asymmetric neuron loss
      with episodic postictal psychosis.
AB  - Rarely are both sides of the hippocampus available for pathological study in a
      patient with intractable temporal lobe epilepsy (TLE). The authors report a
      patient with TLE investigated with bilateral depth electrodes who had an episode
      of postictal psychosis. The patient died 4 weeks after temporal lobectomy of
      unknown reasons, despite complete postmortem examination and clinical evidence of
      postsurgery seizure control. Pathological examination of surgical and autopsy
      hippocampal specimens found bilateral asymmetric neuron losses. However, only the
      resected epileptogenic hippocampus showed the profile of neuron loss typical of
      mesial temporal sclerosis (MTS) and abnormal mossy fiber synaptic reorganization.
      Quantitative depth electroencephalographic (EEG) analysis of the postictal
      psychotic event showed that it was not associated with a cluster of seizures,
      increased postictal depth EEG spike activity, or insufficient antiepileptic
      medication. These results support the hypothesis that ipsilateral hippocampal
      epileptogenesis is associated with MTS and mossy fiber sprouting. The results
      also suggest that the etiology of postictal psychosis in this patient was
      initiated by an ictal event and the behavior apparently depended on seizure
      propagation outside the hippocampus. The relevance of these two findings to the
      literature is discussed.

PMID- 7815151
TI  - One-stage internal fixation and anterior fusion in complex cervical spinal
      disorders.
AB  - The authors describe their experience with the Morscher titanium cervical plate
      with cancellous locking screws in the management of complex cervical spine
      disorders. Fifty patients (32 males and 18 females) with a mean age of 54 years
      (range 10 to 84 years) underwent anterior spinal fixation that extended two to
      five vertebral bodies, using a titanium cervical plate and autogenous bone graft.
      Surgeries were performed for a variety of reasons: one for a congenital lesion,
      five for spinal neoplasms, nine for trauma, and 35 for degenerative arthritides.
      Ten patients had symptomatic kyphoses due to previous laminectomy, failed
      anterior surgery, or trauma. Satisfactory fixation and fusion with no
      neurological deterioration was obtained in all but two cases. Specific
      complications included six cases of dysphagia, one of sepsis, one of Horner's
      syndrome, and one case in which the patient had a fatal myocardial infarction the
      night after surgery. At the end of the follow-up period, fusion was found to have
      occurred in all remaining cases with no outstanding implant-related problems.

PMID- 7815152
TI  - Vertical facet splitting: a special variant of rotary dislocations of the
      cervical spine.
AB  - A special variant of rotary displacement of the cervical spine with vertical
      splitting of an inferior articular process by its articulating partner is
      reviewed. Eighteen patients with unilaterally locked facet joints confirmed by
      computerized tomography were seen between 1986 and 1991. Five patients presented
      with vertical split fractures of an inferior articular process by impaction of
      the superior process of the subjacent vertebra. This specific fracture pattern is
      not accounted for in current classifications. Four males and one female with a
      mean age of 31 years (range 16 to 49 years) were affected. Three of the patients
      showed no neurological deficits. One patient presented with cerebral contusion
      and paresis of the right upper extremity, and in one patient the posterior
      funiculus was involved. Three of the injuries had been sustained recently; the
      other two were of longer duration. Surgical treatment was chosen in the three
      cases of recent injury. In two cases surgery was prompted by neurological
      deficits; in the third case impaction was felt to be of inadequate depth. Surgery
      consisted in fracture reduction and interbody fusion using plates. The two cases
      of long-term fractures were treated conservatively, and ankylosis of the facet
      joints eventually provided adequate stability. If radicular or spinal symptoms
      are absent, this special variant of locked facet joints can successfully be
      treated conservatively leaving the rotary displacement uncorrected, provided
      impaction is adequately deep. The author's experience has shown that indications
      for surgical management are relative rather than absolute in this fracture
      variant and that use of computerized tomography is essential to establish the
      fracture pattern.

PMID- 7815153
TI  - The effect of hemoglobin and its metabolites on energy metabolism in cultured
      cerebrovascular smooth-muscle cells.
AB  - Cerebral arteries in spasm have been found to contain low levels of adenosine
      triphosphate (ATP), and it has been postulated that this change in levels results
      from hypoxia produced by arterial encasement in clotted material. This study was
      undertaken to determine whether any of four blood-derived agents, ferrous
      hemoglobin, methemoglobin, hemin, or bilirubin, is capable of reducing energy
      levels in cerebral artery smooth-muscle cells. Twenty-four-hour exposure of
      cultured canine basilar artery cells to ferrous hemoglobin and bilirubin led to a
      significant decline in ATP levels (to 8.9 nmol/mg protein and 2.8 nmol/mg
      protein, respectively) versus control (16.6 nmol/mg protein); methemoglobin and
      hemin showed no effect. Bilirubin but not hemoglobin was found to interfere with
      electron transport and with creatine phosphokinase activity in intact cells;
      however, bilirubin showed no inhibitory effect on this enzyme in cell-free
      conditions. The findings indicate that hemoglobin and bilirubin may be
      responsible for diminished energy levels in cerebral arteries. These observations
      also suggest that bilirubin may exert its effect on ATP by impairing
      mitochondrial function.

PMID- 7815154
TI  - Basic mechanism of in vitro pulsed-dye laser-induced vasodilation.
AB  - Vasodilation of rabbit carotid arteries induced by a pulsed-eye laser was studied
      in vitro to clarify the underlying mechanism. Artery segments were double
      cannulated in a pressure-perfusion apparatus which, under physiological
      conditions, allows for differential application of various solutions,
      pharmacological agents, and pulsed-dye laser light. Vasoconstriction was
      activated using both pharmacological and nonpharmacological agonists. Laser
      energy at a wavelength of either 480 or 575 nm was applied intraluminally in 1
      microseconds pulses, which caused dilation of the arteries if hemoglobin was
      present in the lumen at sufficient concentration. Induced vasodilation did not
      specifically require the presence of hemoglobin; the same phenomenon could be
      repeated using an inert dye such as Evans blue as an optical absorber of laser
      energy. The optical density of the absorber, the number of applied laser pulses,
      and total amount of applied energy directly influenced the vasodilatory response.
      Laser-induced vasodilation was possible in both normal vessels and vessels
      denuded of endothelium. Pulsed-dye laser-induced vasodilation is therefore not a
      phenomenon mediated through chemical processes, but is rather a purely physical
      process initiated by the optical absorption of laser energy by the intraluminal
      medium, which probably induces cavitation bubble formation and collapse,
      resulting in the vasodilatory response of the vessel.

PMID- 7815155
TI  - Insulin reduction of cerebral infarction due to transient focal ischemia.
AB  - Insulin has recently been shown to ameliorate damage in models of global brain
      ischemia. To determine whether insulin is also neuroprotective in focal ischemia,
      20 rats were given 2 to 3 IU/kg insulin and 10 did not receive treatment prior to
      normothermic transient middle cerebral artery occlusion for 2 hours at a blood
      pressure of 60 mm Hg. To further elucidate whether infarction volume is
      influenced by variations in blood glucose levels within the physiological range,
      blood glucose was raised in 10 of the insulin-treated animals to levels
      comparable with the untreated controls. At 1-week survival, damage was assessed
      using quantitative neuropathological examination of 25 coronal planes. It was
      found that preischemic insulin lowered the mean intraischemic blood glucose level
      from 8.4 +/- 0.2 mM (mu +/- standard error of the mean) in the control group to
      3.4 +/- 0.2 mM and reduced total damage (atrophy plus cortical and striatal
      necrosis), expressed as the percentage of the normal hemisphere, from a control
      of 28.5% +/- 2.9% to 14.5% +/- 1.6% (p < 0.005). Coadministration of glucose and
      insulin resulted in a mean intraischemic blood glucose level of 10.1 +/- 0.5 mM,
      with 27.0% +/- 2.4% total damage (p = 0.96, compared with control). Total
      ischemic damage showed an independent correlation with blood glucose levels (r =
      0.67, p = 0.0018). The findings indicate that insulin benefits transient focal
      ischemia and that reducing the blood glucose from 8 to 9 mM to the low-normal
      range of 3 to 4 mM with insulin dramatically reduces subsequent infarction. The
      data suggest that the neuroprotective mechanism of insulin action in focal middle
      cerebral artery occlusion is mediated predominantly via alterations in blood
      glucose levels. In comparison to global ischemia, focal ischemia appears to show
      only a minor direct central nervous system effect of insulin. In clinical
      situations in which transient focal ischemia to the hemisphere can be
      anticipated, insulin-induced hypoglycemia of a mild degree may be beneficial.

PMID- 7815156
TI  - Antagonism of neutrophil adherence in the deteriorating stroke model in rabbits.
AB  - Adhesion of leukocytes to the endothelium can occur in a few hours after the
      onset of ischemia, and the actions of leukocytes have been suggested to aggravate
      reperfusion injury. Adhesion is a prerequisite for the harmful leukocyte actions.
      Rapid mediation of leukocyte adhesion and aggravation of reperfusion injury can
      occur through production of platelet-activating factor (PAF). The authors
      hypothesized that prevention of leukocyte adhesion during ischemia reperfusion
      would have beneficial effects and that these effects might be enhanced by a PAF
      antagonist. To test this hypothesis, rabbits were anesthetized with pentobarbital
      and subjected to severe spinal cord ischemia (25 minutes) followed by 30 minutes
      of reperfusion, at which time either vehicle, antibody against the CD11/CD18
      (anti-CD) leukocyte adhesion molecule (1 mg/kg), or the anti-CD and PAF
      antagonist, WEB 2086 (3 mg/kg), was administered intravenously and the animals
      were monitored for 6.5 hours. Using a score from 0 to 5, recovery of motor
      function was improved at 5.5 hours by the CD antibody (2.0 +/- 0.5 versus 0.4 +/-
      0.2 in the six animals in the vehicle group, p < 0.05). No further improvement
      was induced by WEB 2086 in the six anti-CD treated animals (1.6 +/- 0.7). Spinal
      cord blood flow (laser Doppler flowmetry) at 6 hours was at the preischemic level
      in the control animals (-7% +/- 20%), but clearly increased in the anti-CD group
      (+73% +/- 29%, p < 0.5). The severity of blood-brain barrier damage in the spinal
      cord gray matter was decreased by the treatments. Extravasation of intravenously
      injected Evans blue albumin (EBA), measured by detection of EBA fluorescence, was
      reduced by approximately 50% in both treated groups (p < 0.05). The number of
      morphologically normal motor neurons in the lumbar anterior horns of the
      infarcted spinal cord showed protection in the seven animals in the anti-CD
      treated group at 6.5 hours: 12.7 +/- 1.7 versus 5.3 +/- 1.6 (vehicle), p < 0.05
      without an additional effect by PAF antagonist 12.2 +/- 2.6 (anti-CD + WEB 2086).
      Our results suggest that ultraacute treatment of reperfusion injury based on
      special inhibition of leukocyte effects may be beneficial. Platelet-activating
      factor antagonism failed to enhance this therapeutic effect, which may suggest
      dependency on a common mechanism.

PMID- 7815157
TI  - Limited protective effects of etomidate during brainstem ischemia in dogs.
AB  - To evaluate etomidate as a neuroprotective agent in the brain stem, 33 dogs were
      divided into seven groups and were exposed to isolated, reversible brainstem
      ischemia in the presence or absence of etomidate using a newly developed canine
      model of brainstem ischemia. Brainstem auditory evoked potentials (BAEP) and
      regional cerebral blood flow were measured during ischemia and for 5 hours after
      reperfusion. This model provides a potential physiological environment in which
      to test the efficacy of putative brainstem ischemic protective strategies. During
      ischemia, BAEP were abolished in all animals. Without etomidate 10 minutes of
      ischemia was of short enough duration to allow complete recovery of BAEP.
      Ischemia of 20 or 30 minutes' duration resulted in minimal recovery. The dose of
      etomidate administered did not suppress BAEP or brainstem cardiovascular response
      to ischemia. In animals receiving etomidate and rendered ischemic for 20 minutes,
      a significant but only temporary recovery in BAEP was seen. Etomidate failed to
      have a significant effect in animals rendered ischemic for 30 minutes. The
      minimal effect of etomidate on the current measures of brainstem function is in
      contrast to etomidate's known suppressive effect on cortical electroencephalogram
      and predicts that etomidate does little to alter brainstem metabolism.
      Etomidate's failure to provide for permanent recovery of BAEP suggests that the
      drug does not give sufficient protection from ischemia to the brainstem neurons
      in the auditory pathway. If these auditory neurons reflect brainstem function as
      a whole, etomidate may not be the protective agent of choice during temporary
      arterial occlusion of posterior circulation.

PMID- 7815158
TI  - Monitoring visual evoked potentials during retraction of the canine optic nerve:
      protective effect of unroofing the optic canal.
AB  - To evaluate the effects of unroofing the optic canal during retraction of the
      optic nerve, the authors monitored changes in visual evoked potentials (VEPs)
      stimulated by a light-emitting diode in the canine model. At rest, an early VEP
      wave was reliably observed with an amplitude of 8.2 +/- 0.6 microV and a latency
      of 51.5 +/- 0.7 msec; this wave was named N50. The intracranial optic nerve was
      retracted using a weight of 5, 10 or 50 g. The earliest change in VEP noted
      during retraction was a reduction in N50 wave amplitude. The length of time
      required until N50 amplitude decreased to 50% of the control group (T50) was 10.7
      +/- 1.8 minutes with a weight of 5 g, 4.9 +/- 0.7 minutes with 10 g, and 2.9 +/-
      0.4 minutes with 50 g, with statistically significant differences between the
      groups. Retraction of the optic nerve with all weights finally resulted in the
      disappearance of the N50 wave. The amplitude of the N50 wave recovered fully to
      control size when retraction was released immediately after the wave disappeared.
      The time course of amplitude recovery did not differ significantly between
      groups. Unroofing the optic canal prolonged the T50 during retraction
      significantly to 20.7 +/- 2.9 minutes with a weight of 5 g, 18.9 +/- 4.2 with 10
      g, and 9.0 +/- 2.4 with 50 g. These results demonstrate that unroofing the optic
      canal can protect the optic nerve from damage during operations that require
      optic nerve retraction.

PMID- 7815159
TI  - Arteriovenous fistula around the ventriculoperitoneal shunt system in a patient
      with a dural arteriovenous malformation of the posterior fossa. Case report.
AB  - A dural arteriovenous malformation (AVM) of the posterior fossa can produce
      persistent tinnitus, convulsions, and dementia. Successful therapeutic
      embolization may result in a complete cure, but in some cases, patients do not
      respond to the treatment. The authors report a patient with a dural AVM of the
      posterior fossa that did not respond to repeated intravascular treatments, but
      resulted in an arteriovenous shunt in the scalp around the ventriculoperitoneal
      shunt system. Although several hypotheses have been proposed on the pathogenesis
      of dural AVMs, the underlying mechanisms remain unknown. The rare complication we
      encountered may shed some light on the pathogenesis of dural AVMs.

PMID- 7815160
TI  - Thalamic syndrome caused by unruptured cerebral aneurysm. Case report.
AB  - A case is reported of a 63-year-old woman with thalamic syndrome as the
      presenting feature of an unruptured cerebral aneurysm. Unruptured aneurysm is a
      rare cause of thalamic syndrome; the possible mechanisms of production of the
      sensory disturbance are discussed.

PMID- 7815161
TI  - Nonvisualization of a large cerebral aneurysm despite high-resolution magnetic
      resonance angiography. Case report.
AB  - The use of magnetic resonance (MR) angiography as a safe, accurate, and reliable
      substitute for invasive cerebral arteriography has been anticipated as
      refinements in this technique are introduced. We present the case of an
      unruptured, 11-mm pericallosal arterial aneurysm not visualized on high
      resolution MR angiography. Although this case may be atypical, we caution against
      complete reliance on this test for exclusion of the presence of cerebral
      aneurysms.

PMID- 7815162
TI  - The use of intraarterial papaverine in the management of vasospasm complicating
      arteriovenous malformation resection. Report of two cases.
AB  - The authors report two cases of treatment by intraarterial papaverine of cerebral
      vasospasm complicating the resection of an arteriovenous malformation (AVM). Both
      cases had successful reversal of vasospasm documented on angiography. In the
      first case sustained neurological improvement occurred, resulting in a normal
      outcome by the time of discharge. In the second case, neurological deterioration
      occurred with the development of cerebral edema. This complication was thought to
      be due to normal perfusion pressure breakthrough, on the basis of angiographic
      arterial vasodilation and increased cerebral blood flow. These two cases
      illustrate an unusual complication of surgery for AVMs and demonstrate that
      vasospasm (along with intracranial hemorrhage, venous occlusion, and normal
      perfusion pressure breakthrough) should be considered in the differential
      diagnosis of delayed neurological deterioration following resection of these
      lesions. Although intraarterial papaverine may be successful in dilating spastic
      arteries, it may also result in pathologically high flows following AVM
      resection. However, this complication has not been seen in our experience of
      treating aneurysmal subarachnoid hemorrhage by this technique.

PMID- 7815163
TI  - A guide to placement of parietooccipital ventricular catheters. Technical note.
AB  - Accurate placement of parietooccipital ventricular catheters can be difficult and
      frustrating. To minimize the morbidity of the procedure and lengthen the duration
      of shunt function, the catheter tip should lie in the ipsilateral frontal horn.
      The authors describe a posterior ventricular guide (PVG) for placement of
      parietooccipital catheters that operates by mechanically coupling the posterior
      burr hole to the anterior target point. In a series of 38 patients who underwent
      ventriculoperitoneal shunting with the assistance of the guide, postoperative
      computerized tomography (CT) scanning revealed that 35 (92.0%) had accurate
      catheter placement. In comparison, a retrospective review of free-hand posterior
      catheter placement revealed good catheter position in only 22 of 43 patients
      (51.1%). The use of the guide added less than 5 minutes to the entire procedure,
      and there were no complications related to its use. The PVG is a simple and
      useful tool that aids in the placement of parietooccipital ventricular catheters.

PMID- 7815164
TI  - Peritoneal cerebrospinal fluid shunt insertion: a technique for protection of the
      abdominal catheter. Technical note.
AB  - A minor modification of the technique of peritoneal cerebrospinal fluid shunt
      insertion allows more anatomical closure of the abdominal wound and may protect
      the shunt from contamination by superficial abdominal would infection.

PMID- 7815165
TI  - Treatment for trigeminal neuralgia.

PMID- 7815166
TI  - Extreme lateral transcondylar approach.

PMID- 7815167
TI  - Cholecalciferol 25-hydroxylation is similar in liver microsomes from male and
      female rats when cholecalciferol concentration is low.
AB  - We compared cholecalciferol 25-hydroxylation in liver microsomes of male and
      female rats. The rate of production of 25-hydroxycholecalciferol was similar in
      liver microsomes from female rats and those from male rats when cholecalciferol
      concentration ranged from 50 to 200 nmol/L. The liver cytosolic fraction
      stimulated the 25-hydroxylase activity of the microsomes up to 100% in both male
      and female rats at 44 nmol/L cholecalciferol. Cytosol metabolized cholecalciferol
      to a currently unidentified metabolite. At 300 nmol/L cholecalciferol, synthesis
      of the cytosolic metabolite was 100% greater than at 100 nmol/L and coincided
      with 32% lower synthesis of 25-hydroxycholecalciferol. These results suggest
      similar 25-hydroxy-lase activity in liver microsomes from male and female rats
      and similar ability of liver cytosol from these rats to stimulate 25
      hydroxylation at low nanomolar concentrations of cholecalciferol, whereas
      inhibitory effects of cytosol at higher concentrations of cholecalciferol were
      shown.

PMID- 7815168
TI  - Early treatment of obese (ob/ob) mice with triiodothyronine increases oxidative
      metabolism in muscle but not in brown adipose tissue or liver.
AB  - We explored the possibility that early replacement of low triiodothyronine (T3)
      may improve the low oxidative metabolism in metabolically important tissues of
      ob/ob mice. Triiodothyronine doses (2.5 to 25.0 micrograms/100 g body wt) were
      injected intraperitoneally into ob/ob and non-ob/ob mice daily from 3 wk until 6
      wk of age. Untreated ob/ob and non-ob/ob mice were injected with saline (pH 9.1).
      Food intake was equalized across all groups. At 6 wk of age, the O2 consumption
      of muscle, white and brown adipose tissues, and hepatocytes was measured. The
      saline-treated ob/ob mice showed lower muscle weights, higher fat pad and liver
      weights, and larger fat cell sizes than saline-treated non-ob/ob mice. In ob/ob
      mice, tissue O2 consumption was the same in muscle, lower in brown and white
      adipose tissues, but higher in liver compared with values in non-ob/ob mice.
      Triiodothyronine treatment in ob/ob mice resulted in lower values for body
      weight, liver weight, hepatocyte number, liver protein, epididymal fat pad
      weight, and white adipocyte number and size than in saline-treated ob/ob mice.
      Triiodothyronine treatment increased soleus muscle, liver and brown adipose
      tissue O2 consumption in non-ob/ob mice. In ob/ob mice, triiodothyronine
      increased only soleus muscle O2 consumption and required higher doses than in non
      ob/ob mice to achieve an effect. These data are consistent with the concept of
      tissue triiodothyronine resistance in ob/ob mice. Low triiodothyronine levels and
      tissue resistance to triiodothyronine might be important early defects in this
      obesity syndrome.

PMID- 7815169
TI  - Nutrient uptake by the hindlimb of growing pigs treated with porcine somatotropin
      and insulin.
AB  - The shift in nutrient partitioning induced by porcine somatotropin (pST) is
      accompanied by a decrease in insulin sensitivity for whole-body glucose uptake.
      The relative contribution of metabolic changes in the hindlimb was investigated
      in eight pigs (55 kg) that had received recombinant pST (120 micrograms/kg) or
      excipient (control) for 7 d. Uptake of metabolites by the hindlimb was measured
      under basal conditions and during hyperinsulinemic-euglycemic clamps at low [14
      ng/(kg.min)] and high [360 ng/(kg.min)] insulin infusion rates. Dextrose infusion
      rate required to maintain euglycemia was used as an index of whole-body glucose
      uptake in response to exogenous insulin. Effects of pST on hindlimb and whole
      body glucose uptake were evident only at physiological levels of insulin (basal
      and low insulin infusion rate). During the low rate of insulin infusion, dextrose
      infusion rate was 79% lower for pST-treated pigs and glucose uptake by the
      hindlimb was 59% lower compared with control pigs. The decrease in glucose uptake
      by the hindlimb was entirely accounted for by the estimated reduction in glucose
      utilization by adipose tissue of the hindlimb. Glucose:oxygen quotients were
      reduced during basal (57%) and low insulin infusion (63%) with pST treatment,
      indicating a change in the pattern of substrate utilization. This is consistent
      with the concept that pST directs nutrients away from adipose and towards muscle
      growth by altering the response of tissues to homeostatic signals such as
      insulin.

PMID- 7815170
TI  - Apolipoprotein mRNA in liver and intestine of rats is affected by dietary beet
      fiber or cholestyramine.
AB  - Rats were fed a cholesterol-free diet with no added fiber (fiber-free) or with 15
      g/100 g beet fiber or 5 g/100 g cholestyramine for 14 d. Final plasma total
      cholesterol concentrations were significantly lower in rats fed beet fiber than
      in those fed fiber-free or cholestyramine diets. This difference was due mainly
      to lower HDL cholesterol concentrations. The group fed beet fiber also tended (P
      < 0.1) to have lower apolipoprotein A-I concentration in plasma. Northern blot
      analysis revealed that the relative concentrations of jejunal apolipoprotein A-I
      and A-IV mRNA were the same in all groups, whereas ileal apolipoprotein A-I and A
      IV mRNA levels were significantly lower in rats fed beet fiber or cholestyramine
      than in those fed the fiber-free diet. Hepatic apolipoprotein E mRNA
      concentrations were the same in all groups, but apolipoprotein A-I mRNA levels
      were significantly lower in rats fed beet fiber than in those fed the other
      diets. Apolipoprotein A-IV mRNA tended (P < 0.1) to be lower in rats fed the beet
      fiber diet. These data suggest that the hypocholesterolemic effect of dietary
      beet fiber is associated with diminished expression of the hepatic apolipoprotein
      A-I gene.

PMID- 7815172
TI  - Fish oil enhances pentachlorobenzene metabolism and reduces its accumulation in
      rats.
AB  - To investigate the influence of dietary fats on the metabolism and excretion of
      pentachlorobenzene (PECB), rats were fed semipurified diets containing soybean
      oil, lard or fish oil (10 g/100 g diet) for 2 wk. Rats then received a single
      dose of PECB by intragastric gavage. Blood concentration of pentachlorophenol
      (PCP), a major metabolite of PECB, was higher after 5 h through d 3 and that of
      PECB was lower after d 5 in the rats fed fish oil than in rats fed the other
      fats. After d 5, the highest ratio of PCP/PECB in the liver was seen in the fish
      oil-fed rats. Furthermore, fish oil intake resulted in a markedly lower
      concentration of PECB in fat tissues, where a large amount of PECB is typically
      distributed due to its lipophilic property. These findings indicate that fish oil
      feeding enhances PECB metabolism, thereby decreasing PECB residues in the body.
      Fish oil-fed rats had a smaller epididymal fat tissue mass compared with lard- or
      soybean oil-fed rats. The small mass of the fat tissues apparently limited the
      accumulation of PECB in those tissues and thus accelerated PECB metabolism in the
      liver.

PMID- 7815171
TI  - Endogenous amino nitrogen collected from pigs with end-to-end ileorectal
      anastomosis is affected by the method of estimation and altered by dietary fiber.
AB  - Endogenous protein loss at the end of the small intestine was determined in two
      experiments using 10 pigs surgically prepared with end-to-end ileo-rectal
      anastomosis to allow total collection of ileal digesta. In the first experiment
      pigs were fed graded protein levels of 0 (protein-free), 55, 110 or 165 g/kg
      diet. Optimal durations for the adaptation and collection periods were found to
      be 4 and 3 d, respectively (combination 4:3), as shown by the higher correlation
      coefficient (r2 = 0.95) between excreted and ingested nitrogen compared with the
      other combinations tested (5:2, 5:3, 9:3, 9:5). The estimated amounts of
      endogenous N and amino acids were less accurate and tended to be smaller (P <
      0.20) when obtained by extrapolation to zero nitrogen intake than when measured
      in pigs fed the protein-free diet. The endogenous protein was rich in proline,
      glutamic acid, glycine, aspartic acid, serine and threonine. In comparison to
      other amino acid patterns, this composition suggested a low bacterial
      contamination of the digesta. In the second experiment three levels of dietary
      fiber from wheat straw, corn cobs and wood cellulose were studied in pigs fed
      protein-free diets. Between 17 and 34 g crude fiber/kg diet, fiber increased the
      endogenous losses of nitrogen and amino acids per kilogram of dry matter intake
      (P < 0.05), but the excretion reached a plateau at higher dietary fiber
      concentration (102 g/kg). In contrast, glucosamine and galactosamine excretion
      increased continuously and linearly (P < 0.05) with fiber intake. We conclude
      that endogenous amino acid loss may be considered constant at usual and high
      levels of the fibrous mixture under study.

PMID- 7815173
TI  - Connective tissue integrity is lost in vitamin B-6-deficient chicks.
AB  - The objective of the present investigation was to characterize further the
      connective tissue disorder produced by pyridoxine (vitamin B-6) deficiency, as
      previously evidenced by electron microscopy. Following the second post-natal
      week, fast growing male chicks were deprived of pyridoxine for a 1-mo period. Six
      weeks post-natally, blood concentrations in the experimental deficiency group had
      declined to deficiency levels as registered by low concentrations of pyridoxal
      phosphate (coenzyme form) in erythrocytes, but did not reach levels associated
      with neurological symptoms. Light microscopic study showed abnormalities in the
      extracellular matrix of the connective tissues. Collagen cross-links and the
      aldehyde contents were not significantly lower in cartilage and tendon collagens
      of vitamin B-6-deficient animals than in age-matched controls; also, their
      proteoglycan degrading protease and collagenase activities measured in articular
      cartilages were not greater. Thus, proteolysis was an unlikely alternative
      mechanism to account for the loss of connective tissue integrity. These results
      point to the need for further investigation into adhesive properties of collagen
      associated proteoglycans or other proteins in vitamin B-6-deficient connective
      tissue.

PMID- 7815174
TI  - Hypercholesterolemia induced by cholesterol- or cystine-enriched diets is
      characterized by different plasma lipoprotein and apolipoprotein concentrations
      in rats.
AB  - This study examined the effects of diet-induced hypercholesterolemia on plasma
      apolipoprotein (apo) concentrations and hepatic apolipoprotein mRNA levels in
      rats. Hypercholesterolemia was induced by feeding rats diets containing an excess
      of either cholesterol or cystine. After cholesterol feeding, plasma apo E and apo
      B concentrations were lower (-65%, P < 0.001) and greater (+39%, P < 0.01),
      respectively, compared with control diet-fed rats. After cystine feeding, plasma
      apo B and apo E concentrations were greater (+46%, P < 0.01 and +75%, P < 0.001,
      respectively) and plasma apo A-IV concentration was lower (-29%, P < 0.001) than
      in rats fed control diet. After cholesterol or cystine feeding, a tendency (one
      way ANOVA, P = 0.08) for greater apo B mRNA level (+42% and +47%, respectively)
      was observed compared with control diet-fed rats. No difference emerged between
      groups for apo E and apo A-I mRNA levels. An opposite effect of cholesterol and
      cystine feeding was shown for apo A-IV mRNA level, i.e., higher after cholesterol
      feeding (+47%, P < 0.05) and lower after cystine feeding (-65%, P < 0.01). From
      this work, it seems that hypercholesterolemia induced by dietary cholesterol or
      by increased cholesterogenesis in cystine-fed rats is characterized by different
      plasma lipoprotein and apolipoprotein concentrations and is associated with
      different apolipoprotein gene expression in the liver.

PMID- 7815175
TI  - A dietary nucleoside-nucleotide mixture inhibits endotoxin-induced bacterial
      translocation in mice fed protein-free diet.
AB  - Nucleosides and nucleotides are important substrates utilized by the intestinal
      mucosa. To determine the relative effect of dietary nucleosides and nucleotides
      on the gut, we investigated the effects of these compounds on endotoxin-induced
      bacterial translocation, cecal bacterial populations and ileal histology in
      protein-malnourished mice. There was an inhibition of gram-negative enteric
      bacteria in the mesenteric lymph node and spleen of the surviving mice fed the
      protein-free diet supplemented with a nucleoside-nucleotide mixture compared with
      the nonsupplemented group. Histologically, the damage to the gut mucosal barrier
      was more pronounced in the nonsupplemented group than in the nucleoside
      nucleotide supplemented group. However, the cecal bacterial populations in the
      groups were not different. The villous height, crypt depth and total wall
      thickness were more developed in the supplemented group compared with the
      nonsupplemented group, indicating that the nucleoside-nucleotide mixture blocked
      bacterial translocation by preventing endotoxin-induced mucosal or epithelial
      damage. These results suggest that the nucleoside-nucleotide mixture could be
      used to inhibit or reduce the incidence of bacterial translocation, decrease
      intestinal injury and improve survival in a lethal model of protein deficiency
      and endotoxemia.

PMID- 7815176
TI  - Dietary fat and fiber alter rat colonic protein kinase C isozyme expression.
AB  - To better understand the biochemical mechanisms by which select fats and fibers
      modulate colonic cell proliferation, we determined the profile of protein kinase
      C (PKC) isozymes and cell proliferation in rat proximal and distal colonic mucosa
      following diet manipulation, because enhanced cell proliferation has been
      correlated with colon cancer incidence. Rats were assigned to one of four diets
      (each with 15 g fat + 6 g fiber/100 g diet) for 3 wk: fiber-free fish oil (FF),
      fiber-free corn oil (FC), cellulose + corn oil (CC), or pectin + corn oil (PC).
      Stead-state levels of colonic mucosal cytosolic and membrane PKC isozymes were
      determined. In vivo cell proliferation was determined by bromodeoxyuridine
      incorporation into DNA. In addition, viable exfoliated colonic epithelial cells
      were isolated from feces using Percoll-bovine serum albumin gradients. We found
      that 1) proximal and distal colonic mucosa possessed different steady-state
      levels and relative proportions of PKC isozymes; 2) PKC alpha and delta
      expression were significantly greater in distal membrane of the PC-fed group
      compared with the other dietary groups; 3) the number of exfoliated cells per 4-h
      fecal collection generally was proportional to the diet-induced changes in cell
      proliferation (PC > FC > CC > FF). These data demonstrate that dietary treatment
      altered colonic PKC isozyme expression, with animals fed the fiber-containing
      diets generally expressing higher steady-state levels of PKC alpha and delta.

PMID- 7815177
TI  - Potential for misclassification of infants' usual feeding practices using 24-hour
      dietary assessment methods.
AB  - Feeding patterns of 131 low income Peruvian infants were assessed by 1574 single
      day studies (12-h observations plus 12-h recall) of dietary intake and by
      mothers' monthly reports of usual feeding practices to determine whether feeding
      pattern classification depends on the assessment method used. Results suggest
      that single-day studies produce a different view of feeding practices than do
      mothers' reports of usual behavior. Exclusive breast-feeding in infants younger
      than 4 mo was observed 25% more often than reported. Non-human milk consumption
      was reported 30% more often than observed. Disagreement between reported and
      observed practices was related by logistic regression analyses to mother's age
      and education, number of children younger than 5 y in the home and infant age and
      illness on the observation day. Most disagreement between reported and observed
      behavior could have been due to daily variation in feeding practices. Consumption
      during the past 24 h should not be used alone as the basis for classifying infant
      feeding practices in survey research.

PMID- 7815178
TI  - Zinc status is not adversely affected by folic acid supplementation and zinc
      intake does not impair folate utilization in human subjects.
AB  - Changes in zinc status in response to folic acid supplementation and the effect
      of zinc intake on folate utilization were evaluated in 12 men (20-34 y old)
      consuming a diet containing 3.5 or 14.5 mg zinc/d for two 25-d intervals.
      Deuterium-labeled folic acid (800 micrograms/d) or a placebo was administered
      orally during each phase. No differences in plasma zinc, erythrocyte zinc,
      urinary zinc, erythrocyte metallothionein or serum alkaline phosphatase, due to
      supplemental folic acid, were detected at either level of zinc intake.
      Differences in the response to folic acid supplementation, due to the level of
      zinc intake, were not detected for serum, erythrocyte or urinary (labeled and
      unlabeled) folate. Within the constraints of this short-term folic acid
      supplementation study, adverse effects on zinc status were not observed and our
      data suggest that folic acid utilization was not influenced by level of zinc
      intake.

PMID- 7815179
TI  - Palmitic acid is absorbed as sn-2 monopalmitin from milk and formula with
      rearranged triacylglycerols and results in increased plasma triglyceride sn-2 and
      cholesteryl ester palmitate in piglets.
AB  - Milk fatty acids contain 20-30% palmitic acid (16:0), with approximately 70% of
      the 16:0 esterified to the sn-2 position of the milk triacylglycerol. Formulae
      containing vegetable and oleo oils contain different amounts of 16:0, but all
      have unsaturated fatty acids esterified to the triacylglycerol sn-2 position.
      Intraluminal triacylglycerol hydrolysis by endogenous lipases produces sn-2
      monoacylglycerols and free fatty acids, which are absorbed and re-esterified in
      the enterocyte for secretion to plasma. The extent of absorption and re
      esterification of sn-2 monoacylglycerols from milk or formula fats in infants is
      unknown. This was studied by feeding piglets sow milk or formulae containing
      similar total saturated fat, 18:1, 18:2(n-6) and 18:3(n-3) with unsaturated fatty
      acids at the sn-2 position or with rearranged triacylglycerols containing
      approximately 30% 16:0, with 70% 16:0 in fatty acids at the sn-2 position.
      Feeding milk or 16:0 on the sn-2 position of formula with rearranged
      triacylglycerols resulted in higher 16:0 esterified to the plasma triacylglycerol
      sn-2 position and in cholesteryl esters than feeding formulae with 0.4 to 4.4%
      16:0 in the sn-2 position fatty acids. The absorption of 16:0 as monopalmitin
      from milk and any metabolic importance in human infants has yet to be determined.

PMID- 7815180
TI  - True absorption and retention of supplemental iron is more efficient when iron is
      administered every three days rather than daily to iron-normal and iron-deficient
      rats.
AB  - Absorption of daily iron supplements is inefficient. Detailed absorption patterns
      of FeSO4 supplements simulating World Health Organization-recommended doses were
      studied in iron-deficient and iron-normal male Sprague-Dawley rats. For 12 d
      after weaning, the rats were fed a premeal containing < 20 (iron-deficient group)
      or 400 micrograms Fe (iron-normal group) twice daily followed by iron-free AIN-76
      diet for 1 h. Then, both groups (iron-deficient and -normal) were divided in
      three groups, one continuing without change and two receiving 4000 micrograms of
      premeal Fe either daily or every 3 d to match intestinal mucosa renewal time.
      Food intake, growth, hemoglobin concentration and periodic 59Fe-labeled iron
      absorption and rate of loss were determined. Iron-deficient rats became anemic,
      and ate and grew less. Iron absorption was stable in normal (34.2%), deficient
      (89.7%) and normal, intermittently supplemented (9.5%) groups. Absorption
      decreased logarithmically in daily supplemented rats, whereas in iron-deficient,
      intermittently supplemented rats absorption decreased slowly and linearly. Rates
      of iron loss were significantly accelerated in daily supplemented rats. Thirteen
      day total iron retention in intermittently supplemented normal and deficient rats
      was 62 and 86%, respectively, of that of daily supplemented rats. Iron
      supplementation timed to match mucosal renewal is more efficient.

PMID- 7815181
TI  - Production of large amounts of [13C]leucine-enriched milk proteins by lactating
      cows.
AB  - During protein metabolism kinetic studies, oral tracers are administered as
      labeled free amino acids and do not necessarily represent the metabolic fate of
      amino acids ingested as proteins. However, sufficient quantities of 13C-labeled
      proteins are not currently available. We here present a new methodology for
      producing large amounts of milk proteins intrinsically labeled with [13C]leucine.
      After surgical preparation, two lactating cows were infused with 80-90 g of L-[1
      13C]leucine for 24-32 h, and milk was collected during and after the infusion.
      Casein and whey protein fractions were purified by membrane separation
      techniques. Arteriovenous balance across the udder indicated a very efficient
      extraction of leucine by the mammary gland. Five batches of pure casein and whey
      proteins, totaling 3854 g of protein of excellent bacteriological quality, were
      obtained. Two thirds of these proteins had [13C]leucine enrichments ranging from
      10.5 to 19.4% ([13C]leucine atom percent excess). The overall tracer recoveries
      were 22 and 27% (cows 1 and 2, respectively). Thus, pure milk proteins were
      produced in large amounts with sufficient 13C enrichment to be used in human
      protein metabolism studies.

PMID- 7815182
TI  - Folate catabolism is related to growth rate in weanling rats.
AB  - The relationship between growth rate and folate catabolism was determined using a
      catch-up growth model in weanling rats. A recently developed HPLC method was
      employed to compare the urinary excretion of the major end product of folate
      catabolism, acetamidobenzoylglutamate (apABGlu), in normally growing (n = 8) and
      age-matched growth-restricted (n = 8) weanling animals, during and after food
      restriction. During the 12-d period of food restriction in which restricted rats
      were fed (per gram of body weight) at a level of 50% of the required dietary
      intake for normal growth, apABGlu excretion was significantly higher in normally
      growing rats compared with growth-restricted rats. In the latter group after
      restriction, apABGlu concentrations increased markedly, tending to exceed those
      of normally growing rats of comparable age. Thus growth retardation resulted in a
      decreased rate of folate catabolism, whereas accelerated growth following dietary
      restriction was associated with an increase in catabolism. Because early growth
      in rats is predominantly hyperplastic, these results suggest that the rate of
      folate catabolism is related to folate utilization in cell division.

PMID- 7815183
TI  - Acute cerebral edema as part of the syndrome of hepatic encephalopathy in an
      individual with chronic liver disease: a case report.
AB  - An unusual case of acute cerebral edema as part of the syndrome of portal
      systemic encephalopathy in an individual with established chronic liver disease
      is reported. Several episodes of edema occurred with clinically important
      increases in the blood ammonia level.

PMID- 7815184
TI  - Microbiological flora and nail polish: a brief report.
AB  - Removing nail polish and prosthetic nails from operating room (OR) personnel
      prior to scrubbing and from patients prior to hand surgery is recommended but not
      practiced in many hospitals. There is concern that nail polish can act as a
      vehicle for the transfer of infectious agents. This study was designed to
      determine the incidence of microbiological flora of nail polish in a clinical
      setting.

PMID- 7815185
TI  - Survival following organ transplantation in an Oklahoma institution, 1985-1993.
AB  - Since 1985, a total of 413 patients have undergone 439 solid organ transplants at
      the authors' institution. The current actuarial one-year survival rate of
      patients undergoing heart, kidney, lung, or liver transplantation at our center
      is 94%, 90%, 87%, and 91%, respectively. Five-year survival of heart and kidney
      recipients is 80% and 75%, respectively. In view of these excellent results and
      the excellent quality of life that successful organ transplants provide patients
      with end-stage organ failure, every possible effort should be made to increase
      organ donation.

PMID- 7815186
TI  - Creating more generalists: physician reform by reason ... or by mandate?

PMID- 7815187
TI  - Photochemistry of DNA and related biomolecules: quantum yields and consequences
      of photoionization.
AB  - The reactions of nucleic acids and constituents, which can be induced by laser UV
      irradiation, are described. Emphasis is placed on the quantum yields of various
      stable photoproducts of DNA and model compounds upon irradiation at 193, 248, 254
      or 266 nm. In particular, those quantum yields and processes are discussed which
      involve photoionization as the initial step and occur in aqueous solution under
      well defined conditions, e.g. type of atmosphere. The efficiencies of some
      photoproducts, with respect to photoionization using irradiation at 193 or 248
      nm, are presented. Radical cations of nucleobases are important sources of damage
      of biological substrates since they can cause lesions other than dimers and
      adducts, e.g. strand breakage, abasic sites, crosslinks or inactivation of
      plasmid and chromosomal DNA. While competing photoreactions, such as hydration,
      dimerization or adduct formation, diminish the selectivity of the photoionization
      method, a combination with model studies on pyrimidine- and purine-containing
      constituents of DNA has brought about an enhanced insight into the reaction
      mechanisms. The knowledge concerning the lethal events in plasmid and cellular
      DNA has been greatly improved by correlation with the chemical effects obtained
      by gamma-radiolysis, vacuum-UV (< 190 nm) and low-intensity irradiation at 254
      nm.

PMID- 7815188
TI  - Photophysical and photobiological activities of a porphyrin peptide fraction
      derived from haemoglobin.
AB  - In a previous study, we described the preparation of a porphyrin peptide
      hydrolysate from haemoglobin, its isolation and its analysis by high performance
      liquid chromatography (HPLC) and fast atom bombardment (FAB) mass spectrometry.
      The purpose of the present paper is to test the photosensitizing activity of this
      fraction. We determined the singlet oxygen quantum yield (phi delta) in order to
      quantify the efficiency of the porphyrin peptide fraction. The quantum yield is
      about phi(1O2)=0.06. An analysis of the phototoxic effect on tumour cells in
      culture was performed and compared with haematoporphyrin derivative (HpD), the
      only photosensitizer in clinical use at present. The phototoxicity of the
      porphyrin peptide fraction is weaker than that of HpD. However, for a porphyrin
      dose of 50 micrograms ml-1, the difference in phototoxicity is low, and in the
      absence of irradiation porphyrin peptides are less toxic than HpD. These results
      suggest that porphyrin peptides could be potent photosensitizers; moreover, they
      are of great interest since they allow the solubilization of hydrophobic
      porphyrins and could be applied in the future as insoluble photosensitizer
      carriers.

PMID- 7815189
TI  - Photosensitizer targeting in photodynamic therapy. II. Conjugates of
      haematoporphyrin with serum lipoproteins.
AB  - Conjugates between haematoporphyrin (HP) and human low-density lipoprotein (LDL),
      human high-density lipoprotein (HDL) and bovine HDL have been prepared, purified
      and characterized. HP-LDL is aggregated possibly via interparticle apoB protein
      cross-linking. HP-HDL human and bovine conjugates show different degrees of
      intraparticle apoA polypeptide cross-linking. Receptor-mediated endocytosis of HP
      LDL by NIH 3T3 cells is inferred from the increased uptake observed when LDL
      receptors are upregulated. HP-LDL uptake into HT29 cells faces competition from
      unlabelled LDL, albeit at rather high doses. HP-HDL uptake is also inhibited by
      LDL, suggesting that both lipoprotein conjugates may have cell-surface binding
      sites in addition to the specific LDL (apoB) receptor. J774.2 macrophages avidly
      accumulate HP-LDL, retaining most of the fluorescence and some of the protein
      while degrading the remainder. Oxidized LDL species compete in these processes,
      with the major effect on protein degradation. Chloroquine has little effect on
      the fluorescence uptake but inhibits protein degradation (and hence enhances
      protein accumulation). HP-HDL is also avidly taken up by J774.2 cells, but in the
      case of the bovine material with a sigmoidal concentration dependence. This is
      consistent with prior aggregation before the particles can be endocytosed.
      P388.D1 cells, which appear to be less activated than the J774.2 line, take up
      less fluorescence and retain and degrade less protein, but still to higher
      extents than observed for non-phagocytic cells. We conclude that photosensitizer
      lipoprotein conjugates can be taken up in large amounts by cells possessing
      scavenger receptors and/or phagocytic activity, and that this may be a means of
      targeting photodynamic therapy.

PMID- 7815190
TI  - Tuning the mechanism of DNA cleavage photosensitized by ruthenium
      dipyridophenazine complexes by varying the structure of the two non intercalating
      ligands.
AB  - The influence of the nature of ligands on the efficiency of ruthenium complexes
      for photosensitizing DNA cleavage was investigated. Ru(bipy)2dppz2+ and
      Ru(bpz)2dppz2+ were selected as DNA breakers on the basis of their high affinity
      for DNA due to the presence of a dppz ligand which can partially intercalate in
      the major groove of DNA. Their photosensitizing properties were compared to those
      of Ru(bipy)3(2+), a complex which binds to DNA with a far lower constant. Upon
      irradiation, these complexes promoted the formation of single strand breaks in
      supercoiled phi X 174 DNA. Unexpectedly, Ru(bipy)2dppz2+ was found to be less
      efficient than Ru(bipy)3(2+) whatever the dye concentration or the [base
      pair]/[Ru] molar ratio r. Scavenging experiments have shown that the oxidative
      DNA cleavage induced by Ru(bipy)2dppz2+ mainly results from a Type II mechanism.
      The behavior of Ru(bipy)2dppz2+ was different: this compound was clearly more
      efficient than Ru(bipy)3(2+) as DNA breaker and its efficiency was not modified
      by the presence of oxygen or by addition of scavengers of reactive oxygen
      species. In this case, a mechanism involving electron transfer between the
      excited state of the ruthenium complex and the guanine residue was proposed in
      agreement emission lifetime measurements. The change in mechanism observed
      between Ru(bipy)2dppz2+ and Ru (bipy)2dppz2+ results from an increase of the
      reduction potential of the ruthenium complexes in the excited state, which
      appears to be the main factor controlling the efficiency.

PMID- 7815191
TI  - Peroxidation of model lipoprotein solutions sensitized by photoreduction of
      ferritin by 365 nm radiation.
AB  - A mechanistic study involving the 365 nm irradiation of aerated, phosphate
      buffered solutions of human high-density lipoproteins (HDL3 fraction) and
      ferritin was undertaken. The 365 nm irradiation of phosphate-buffered horse
      spleen ferritin solutions induces the release of Fe2+ in the medium. The initial
      quantum yield of Fe2+ release on irradiation is 0.002. This quantum yield is
      oxygen independent. The 365 nm irradiation of mixtures of HDL and ferritin leads
      to alterations in apolipoproteins as revealed by tryptophan (Trp) oxidation and
      electrophoretic pattern modification. In parallel with protein damage, lipid
      peroxidation is induced as shown by hydroperoxide and thiobarbituric acid
      reactive substances (TBARS) formation. These peroxidations are strongly reduced
      in 0.1 M formate solution, which suggests chain initiation by .OH radicals or
      subsequent radicals produced by .OH. They are completely inhibited by
      desferrioxamine, consistent with propagation by Fe2+ ion. By contrast incubation
      of HDL in the presence of ferritin and FeSO4 induces only poor auto-oxidation.
      The biological relevance of this study is discussed.

PMID- 7815192
TI  - Encapsulation of the thrombolytic enzyme, brinase, in photosensitized
      erythrocytes: a novel thrombolytic system based on photodynamic activation.
AB  - In order to circumvent many of the problems associated with the systemic
      administration of agents used in thrombolytic therapy, it was decided to
      investigate the possibility of using erythrocytes as carriers and delivery
      vehicles for these agents. The enzyme brinase, a fibrinolytic enzyme produced by
      Aspergillus oryzae, was loaded into rabbit erythrocytes using electroporation.
      The loading index for this enzyme was found to be 60% and incorporation appeared
      to be relatively stable over a period of 4 h. In order to facilitate the
      predetermined release of the loaded component from the erythrocytes, they were
      photosensitized using haematoporphyrin derivative (HPD) and release was
      demonstrated within 5 min of photoactivation. Inclusion of the loaded,
      photosensitized system into clotting blood and subsequent exposure to light
      demonstrated almost complete lysis of the clot. We believe that this system
      exhibits potential for use in thrombolytic therapy.

PMID- 7815193
TI  - 4,6,4'-Trimethylangelicin induces interstrand cross-links in mammalian cell DNA.
AB  - 4,6,4'-Trimethylangelicin, a well-known effective photosensitizer described as a
      pure monofunctional reactant with DNA, can induce interstrand cross-links in
      mammalian cell DNA in vivo (about 15% relative to 8-methoxypsoralen), as observed
      using alkaline elution and Chinese hamster ovary cells. Experiments performed
      using the two-step irradiation method and HeLa cells support these data. In
      contrast with 4,6,4'-trimethylangelicin, 4'-methylangelicin and 4,4'
      dimethylangelicin do not form interstrand cross-links. These results are
      consistent with those recently reported by Chen et al. (X. Chen, J. Kagan, F.
      Dall'Acqua, D. Averbeck and E. Bisagni, J. Photochem. Photobiol. B: Biol, 22
      (1994) 51-57) using pBR322 and M13 DNA. The cross-linking ability of 4,6,4'
      trimethylangelicin does not seem to be related to a particular feature of these
      DNAs but to the compound itself.

PMID- 7815194
TI  - Photoproduct formation during irradiation of tissues containing protoporphyrin.

PMID- 7815195
TI  - Cancer in children with primary or secondary immunodeficiencies.

PMID- 7815196
TI  - Glucose-6-phosphate dehydrogenase deficiency and carboxyhemoglobin concentrations
      associated with bilirubin-related morbidity and death in Nigerian infants.
AB  - Our objective was to determine whether glucose-6-phosphate dehydrogenase (G6PD)
      deficiency and elevated carboxyhemoglobin (COHb) levels correlated with bilirubin
      related morbidity and mortality rates. For this purpose, we studied 55 clinically
      jaundiced infants admitted to a rural mission hospital in southern Nigeria. Total
      serum bilirubin levels (range, 80 to 1016 mumol/L (4.7 to 59.4 mg/dl)) correlated
      with the percentage COHb concentrations (COHb = 0.45 + 0.08 Total serum
      bilirubin; r = 0.72). Infants were divided into two groups of equal size around
      the median COHb concentration (COHb range, 0.43% to 5.93% (median = 1.40%), with
      ambient carbon monoxide of 0.65 +/- 0.03 microL/L). The COHb levels > or = 1.40%
      were associated with the need for exchange transfusion (15/28, or 54%, vs 5/27,
      or 19%; p < 0.01) and with an increased incidence of clinical findings compatible
      with kernicterus (9/28, or 32%, vs 0/27, or 0%; p < 0.01). Mortality rate was 29%
      (8/29) among infants with higher COHb levels, and 7% (2/28) in those with lower
      levels (p = 0.08). Thirty-one percent (14/45) of the clinically jaundiced infants
      tested had G6PD deficiency. Thirty-six percent of the infants with G6PD
      deficiency died with presumed kernicterus, compared with only 3% (1/31) of the
      infants with a normal G6PD screening test result (p < 0.01). These data suggest
      that G6PD deficiency and increased bilirubin production, as indexed by COHb, are
      associated with jaundice-related morbidity and death in Nigerian infants.

PMID- 7815197
TI  - Internal potassium shift in premature infants: cause of nonoliguric hyperkalemia.
AB  - To study the pathophysiology of nonoliguric hyperkalemia, we measured serum
      potassium concentration and external K balance (intake and excretion), and
      estimated internal K balance (a shift from intracellular space to extracellular
      space) in 24 nonoliguric premature infants during the first 72 hours after birth.
      Data were analyzed from two aspects: gestational age (group 1, 24 to 28 weeks, n
      = 9; group 2, 29 to 32 weeks, n = 9; group 3, 33 to 36 weeks, n = 6) and
      postnatal age (0 to 72 hours). Serum K concentration rose from baseline (0 hour)
      to 24 hours in groups 1 and 2 (p < 0.01) but did not rise in group 3. The
      external K balance was negative in all groups during the study period, and was
      more negative in the more premature infants (group 1 > group 2 > group 3) during
      the second 24 hours. There was a significant difference (p < 0.01) between the
      internal K balance of the three groups during the first 24 hours (group 1 > group
      2 > group 3), and the K shift decreased significantly (p < 0.05) during the study
      period in groups 1 and 2. The more premature the infants, the larger the K shift
      and the larger the rise in serum K concentration during the first 24 hours, and
      the more negative the external K balance after 24 hours. These data indicate that
      K loading caused by the K shift associated with prematurity produces a rapid rise
      in serum K concentration, resulting in an increase in urinary K excretion. We
      conclude that an internal K shift inversely proportional to gestational and
      postnatal age is the primary cause of nonoliguric hyperkalemia in very premature
      infants.

PMID- 7815198
TI  - Progression of premature thelarche to central precocious puberty.
AB  - To evaluate whether girls with premature thelarche progress to central precocious
      puberty (CPP) and to analyze their clinical and hormonal characteristics, we
      retrospectively examined 100 girls with premature thelarche who were followed for
      several years. Fourteen of the patients with characteristics diagnostic of
      premature thelarche (isolated breast development before age 8 years, bone age
      advancement within 2 SD of normal, normal growth velocity, follicle-stimulating
      hormone-predominant response to luteinizing hormone-releasing hormone) progressed
      during follow-up to precocious or early central puberty (progressive breast size
      increase, bone age acceleration, and significant decrease in predicted adult
      height). The chronologic age of this group of 14 girls was 5.1 +/- 2.0 years at
      the onset of premature thelarche and 7.8 +/- 0.6 years (mean +/- SD) after
      progression to central early or precocious puberty. Pelvic ultrasonography showed
      significant differences in measurements between the time of diagnosis of
      premature thelarche and progression to CPP. Nine of these patients required
      treatment, three with cyproterone acetate and six with luteinizing hormone
      releasing hormone analogs, and all responded as expected for classic CPP. At
      baseline evaluation, no clinical or hormonal characteristics could be established
      that separated the 14 children who progressed to precocious or early puberty from
      the 86 girls who did not. We conclude that premature thelarche is not always a
      self-limited condition and may sometimes accelerate the timing of puberty.

PMID- 7815199
TI  - Use of the urine-to-blood carbon dioxide tension gradient as a measurement of
      impaired distal tubular hydrogen ion secretion among neonates.
AB  - To evaluate the utility of the urinary-minus-blood partial pressure of carbon
      dioxide (U-B PCO2) gradient for the diagnosis of distal renal tubular acidosis in
      neonates, we measured the U-B PCO2 gradient corresponding to different urinary
      bicarbonate concentrations in 40 neonates. The U-B PCO2 gradient in these
      neonates had a significant linear relationship to the urinary bicarbonate
      concentration. When the urinary bicarbonate concentration was > 10 mmol/L, in all
      the neonates the U-B PCO2 could be increased above the 20 mm Hg level. We
      conclude that it is appropriate to determine the U-B PCO2 gradient as an index of
      distal urinary acidification and that it is a necessary test for diagnosis of
      distal renal tubular acidosis in neonates.

PMID- 7815200
TI  - Newborn screening for congenital adrenal hyperplasia in New Zealand.
AB  - OBJECTIVE: To evaluate the efficacy and efficiency of newborn screening for
      classic congenital adrenal hyperplasia (CAH) in New Zealand. DESIGN: All infants
      younger than 6 weeks of age identified by newborn screening between December 1984
      and December 1993 were included. RESULTS: 23 cases of classic CAH (20 salt
      losers) were identified. The incidence of classic CAH was 1 in 23,344. Screening
      identified 3 of 9 virilized female infants whose disease had not been detected
      clinically. Screening alone identified all 11 male infants. Notification of cases
      occurred at 11 +/- 3 days of age. There was a delay in treatment of the group
      identified by screening alone (n = 14) until 13 days of age (range, 4 to 35
      days); at that time 11 infants had hyponatremia and 10 had hyperkalemia. Symptoms
      of vomiting, poor feeding, and shock were common after 10 days of age (2/10, < 10
      days, and 8/8, 11 to 16 days of age). CONCLUSIONS: Newborn CAH screening is the
      only method of identifying male infants with classic CAH without a family history
      of CAH before symptoms develop, as well as a significant portion of overlooked
      virilized female infants. So that clinical or significant biochemical
      deterioration can be avoided, pediatrician notification of screening results and
      treatment should be started before 10 days of age.

PMID- 7815201
TI  - Reference ranges for newer thyroid function tests in premature infants.
AB  - OBJECTIVE: To establish reference ranges for recently developed assays of thyroid
      function in premature infants. METHODS: We measured serum free thyroxine (T4) by
      direct equilibrium dialysis and serum thyrotropin by a sensitive immunometric
      method in 104 preterm infants (25 to 36 weeks of gestational age) during the
      first week of life. RESULTS: The free T4 level correlated positively with
      gestational age (p < 0.0001; r2 = 0.09) and differed significantly between
      adjacent gestational age groups (p < 0.05). Free T4 concentrations (mean +/- SD)
      for the 25- to 27-, 28-to 30-, 31- to 33-, and 34- to 36-week groups were 18.0 +/
      5.2, 25.7 +/- 9.0, 30.9 +/- 9.0, 36.0 +/- 10.3 pmol/L (1.4 +/- 0.4, 2.0 +/- 0.7,
      2.8 +/- 0.8 ng/dl), respectively. Two reference ranges for free T4 were
      determined, one for 25 to 30 weeks (6.4 to 42.5 pmol/L (0.5 to 3.3 ng/dl) and one
      for 31 to 36 weeks (16.7 to 60.5 pmol/L (1.3 to 4.7 ng/dl)). The logarithm of the
      value for thyrotropin correlated positively with gestational age (p < 0.001; r2 =
      0.08); one reference range of 0.5 to 29 mU/L was determined for thyrotropin.
      CONCLUSION: This study extends information on thyroid function of preterm infants
      and establishes reference ranges for this population.

PMID- 7815202
TI  - Vitamin A and E status in very low birth weight infants: development of an
      improved parenteral delivery system.
AB  - Plasma vitamin A and E levels were inadequate in very low birth weight infants
      receiving a continuous infusion of a parenteral multivitamin preparation, 1.5
      ml/kg per day, in dextrose-amino acid solution. A new delivery system using 2
      ml/kg per day, infused for 6 hours from the first day of life, avoided loss
      during infusion and significantly improved plasma vitamin A and E levels during
      the first 28 days of life in very low birth weight infants.

PMID- 7815203
TI  - Possible fetal effects of cervical dilation and uterine curettage during the
      first trimester of pregnancy.
AB  - We describe two malformed infants whose mothers had cervical dilation and uterine
      curettage. One mother had the procedure at 8 weeks and the other at 6 weeks of
      gestation. One infant had a facial cleft, hypertelorism, scalp defects, brain
      malformations, and absent fingernails and a constricting band on the fourth and
      fifth fingers. The other infant had an area of diminished scalp hair, vertebral
      anomalies, and a heart defect.

PMID- 7815205
TI  - Successful treatment of Finnish congenital nephrotic syndrome with captopril and
      indomethacin.
AB  - Two infants with biopsy-proven microcystic Finnish congenital nephrotic syndrome
      (onset at birth) were treated with a combination of captopril and indomethacin
      for 2 1/2 and 2 years, respectively; they had a marked reduction of urinary
      protein excretion without further need for albumin infusions. One infant has end
      stage renal disease; the other infant's glomerular filtration rate has remained
      within normal limits.

PMID- 7815206
TI  - Treatment of intractable gastrointestinal manifestations of chronic granulomatous
      disease with cyclosporine.
AB  - Gastrointestinal manifestations of chronic granulomatous disease of childhood
      include granulomatous inflammatory bowel disease. Severe colitis and perirectal
      disease developed in a 12-year-old boy with chronic granulomatous disease while
      he was receiving interferon gamma therapy. The boy had a deficiency of the 22 kd
      light chain of the cytochrome b heterodimer. After conventional medical therapy
      proved to be ineffective, a rapid clinical response was obtained to cyclosporine.

PMID- 7815204
TI  - Use of a visual panel detection method for drugs of abuse: clinical and
      laboratory experience with children and adolescents.
AB  - We evaluated the Triage panel for drugs of abuse, a visual method that
      simultaneously detects seven distinct drug classes in a single aliquot of urine,
      by use of 1214 urine specimens obtained from children and adolescent patients
      whose clinical findings warranted a toxicology evaluation. A total of 295
      positive results were confirmed by gas chromatography-mass spectrometry.
      Additional toxicology investigations were not performed on specimens with
      negative results unless the clinical findings did not correspond with the urine
      Triage results. The positive predictive value of the test was found to be > 85%
      for detection of barbiturates, cannabinoid metabolite, cocaine metabolite, and
      opiates; for the benzodiazepines the positive predictive value was 77%. Positive
      predictive values were 53% for amphetamines and 40% for phencyclidine, although
      only five specimens were available for evaluation of the latter drug. Correlation
      between clinical findings of patients and results from the Triage test were good
      except for ingestion of sympathomimetic amines (because of selectivity of the
      antibodies used in the test for amphetamines) and in patients receiving either
      antianxiety or antidepressant drugs (some members of these classes of drugs or
      their metabolites appeared to cross-react with the benzodiazepine test). The
      primary advantages of the Triage test were the rapid turnaround time, the ease
      with which a specimen could be processed, and the ability to use rapidly provided
      information as part of a differential diagnosis.

PMID- 7815207
TI  - Healing of rickets during vitamin D therapy despite defective vitamin D receptors
      in two siblings with vitamin D-dependent rickets type II.
AB  - We report the healing of severe rickets despite hypocalcemia in two siblings with
      absent vitamin D receptors; long periods of treatment with excessive doses of
      vitamin D led to relative hypoparathyroidism and a return to normal of calcium
      metabolism during calcitriol treatment. This finding suggests that some other
      regulating factor may substitute for the defective vitamin D receptor.

PMID- 7815208
TI  - Increased fat oxidation in prepubertal obese children: a metabolic defense
      against further weight gain?
AB  - The purpose of this study was to measure postabsorptive fat oxidation at rest and
      to assess the association between fat mass and fat oxidation rate in prepubertal
      children, who were assigned to two groups: 35 obese children (weight, 44.5 +/-
      9.7 kg; fat mass; 31.7 +/- 5.4%) and 37 nonobese children (weight, 30.8 +/- 6.8
      kg; fat mass, 17.5 +/- 6.7%). Postabsorptive fat oxidation expressed in absolute
      value was significantly higher in obese than in nonobese children (31.4 +/- 9.7
      mg/min vs 21.9 +/- 10.2 mg/min; p < 0.001) but not when adjusted for fat-free
      mass by analysis of covariance with fat-free mass as the covariate (28.2 +/- 10.6
      mg/min vs 24.9 +/- 10.5 mg/min). In obese children and in the total group, fat
      mass and fat oxidation were significantly correlated (r = 0.65; p < 0.001). The
      slope of the relationship indicated that for each 10 kg additional fat mass,
      resting fat oxidation increased by 18 gm/day. We conclude that obese prepubertal
      children have a higher postabsorptive rate of fat oxidation than nonobese
      children. This metabolic process may favor the achievement of a new equilibrium
      in fat balance, opposing further adipose tissue gain.

PMID- 7815209
TI  - C. Henry Kempe.

PMID- 7815210
TI  - Incidence of liver disease in patients with cystic fibrosis and meconium ileus.

PMID- 7815211
TI  - Short-term, high-dose corticosteroid therapy in childhood acute immune
      thrombocytopenic purpura.

PMID- 7815212
TI  - Diagnostic accuracy of urinary tract infection and subsequent development of
      renal scars.

PMID- 7815213
TI  - Local reactions to luteinizing hormone releasing hormone analog therapy.

PMID- 7815214
TI  - Hypotension in preterm infants.

PMID- 7815215
TI  - Terbutaline powder for acute asthma.

PMID- 7815216
TI  - Familial Guillain-Barre syndrome subsequent to Campylobacter jejuni enteritis.

PMID- 7815218
TI  - Pediatric subspecialties and general academic pediatric training.

PMID- 7815217
TI  - Measured versus predicted resting energy expenditure in infants: a need for
      reappraisal.
AB  - The reliability of commonly used predictive equations for estimating energy
      expenditure in infants in both health and disease was assessed by comparing
      resting energy expenditure (REE, measured by indirect calorimetry) in relation to
      weight, height, and body cell mass (by total body potassium analysis) with
      predictive equations (Harris-Benedict, Food and Agriculture Organization/World
      Health Organization/United Nations University (FAO/WHO/UNU), Schofield weight
      only, and Schofield weight-and-height equations) in 36 healthy infants (age 0.43
      +/- 0.27 years; 19 male) and in 9 infants with cystic fibrosis (age 0.41 +/- 0.30
      years; 4 male). Mean +/- SD REE for healthy boys was 0.205 +/- 0.019 MJ kg-1 day
      1 and for healthy girls 0.217 +/- 0.026 MJ kg-1 day-1. Infants with cystic
      fibrosis had a significantly higher REE (0.258 +/- 0.034 vs 0.210 +/- 0.024 MJ kg
      1 day-1; p < 0.005). Compared with measured values, predicted REE values varied
      markedly among equations, overestimating REE in healthy infants (Harris-Benedict
      equation, 182% +/- 63% (SD) of measured values; FAO/WHO/UNU equation, 104% +/-
      14%; Schofield weight-only equation, 107.5% +/- 14%; and Schofield weight-and
      height equation, 106% +/- 11%) and underestimating REE in those with cystic
      fibrosis (84% to 88% for the FAO/WHO/UNU, Schofield weight-only, and Schofield
      weight-and-height equations) except the Harris-Benedict equation (152%). On
      regression analysis both weight and body cell mass were related significantly to
      REE (r2 = 0.87 and r2 = 0.61, respectively) for normal infants and (r2 = 0.92 and
      r2 = 0.94) for those with cystic fibrosis. Using a generalized linear model of
      variance, we saw a significant (p < 0.001) variability among all REE measures.
      Thus we could rely on none of the predictive equations to give an accurate
      estimate of REE, and hence energy and fluid requirements, in individual infants.
      We suggest that when accurate estimates are needed, measurement of REE in
      individual infants should be attempted, especially in disease states, and that
      the continued use of current formulas should be reexamined.

PMID- 7815219
TI  - Normal energy expenditure in the infant with presymptomatic cystic fibrosis.
AB  - To investigate whether a fundamental lesion in energy metabolism is a feature of
      cystic fibrosis, we measured total energy expenditure using the doubly labeled
      water technique in 19 infants with presymptomatic cystic fibrosis (0.8 to 6.6
      months of age) identified through newborn screening. Total energy expenditure
      data collected in a cohort of healthy infants by the same method were used for
      comparison. Energy balance studies were additionally performed in 10 of the
      infants with cystic fibrosis. Total energy expenditure levels in infants with
      cystic fibrosis, expressed as either kilocalories per day or kilocalories per
      kilogram of fat free mass per day, did not differ from control levels. When
      expressed on the basis of body weight (in kilocalories per kilogram per day),
      expenditure levels in infants with cystic fibrosis were greater (p < 0.05) than
      control levels. No differences in expenditure were observed between those infants
      who were homozygous (n = 10) for the delta F508 mutation and the heterozygous
      infants (n = 7), regardless of how expenditure was expressed. Assessment of
      energy balance indicated that infants with cystic fibrosis grow at a normal rate
      for metabolizable energy intakes similar to those reported for healthy infants.
      We conclude that there are no differences in energy expenditure between infants
      with presymptomatic cystic fibrosis and healthy infants, once differences in body
      composition are taken into account. This finding indicates that the primary
      cystic fibrosis defect is not an energy-requiring one.

PMID- 7815220
TI  - Chronic constipation as a symptom of cow milk allergy.
AB  - Twenty-seven consecutive infants (mean age, 20.6 months) with chronic
      "idiopathic" constipation were studied to investigate the possible relation
      between constipation and cow milk protein allergy (CMPA). The infants were
      initially observed on an unrestricted diet, and the number of stools per day was
      recorded. Subsequently the infants were put on a diet free of cow milk protein
      (CMP) for two periods of 1 month each, separated by two challenges with CMP.
      During the CMP-free diet, there was a resolution of symptoms in 21 patients;
      during the two consecutive challenges, constipation reappeared within 48 to 72
      hours. In another six patients the CMP-free diet did not lead to improvement of
      constipation. Only four of the patients who improved on the CMP-free diet had
      concomitant symptoms of suspected CMPA, but a medical history of CMPA was found
      in 15 of the 21 patients cured and in only one of the six patients whose
      condition had not improved (p < 0.05); in addition, in 15 of the 21 cured
      patients, results of one or more laboratory tests (specific IgE, IgG, anti-beta
      lactoglobulin, circulating eosinophils) were positive at the time of diagnosis,
      indicating hypersensitivity, compared with one of the six patients whose
      condition did not improve (p < 0.05). The endoscopic and histologic findings at
      the time of diagnosis showed proctitis with monocytic infiltration in two
      patients cured with the CMP-free diet; after 1 month on this diet, they were
      completely normal. We conclude that constipation in infants may have an allergic
      pathogenesis.

PMID- 7815221
TI  - Spectrum of disease associated with anti-neutrophil cytoplasmic autoantibodies in
      pediatric patients.
AB  - Anti-neutrophil cytoplasmic autoantibodies (ANCA) are usually determined during
      the diagnostic evaluation of systemic vasculitis and glomerulonephritis syndromes
      in adult patients, but few pediatric patients with ANCA have been reported. We
      describe five pediatric patients with ANCA and glomerulonephritis, with and
      without upper or lower respiratory tract disease. We compared these five patients
      and six previously described patients to affected adults; the spectrum of ANCA
      associated disease appears to be similar in adults and children, but a female
      predominance may exist in the pediatric patients. Pediatric patients often had
      end-stage renal disease within 1 year after onset. We conclude that ANCA is a
      useful diagnostic tool in both pediatric and adult patients with systemic
      vasculitis and glomerulonephritis.

PMID- 7815222
TI  - Somatosensory evoked potentials for prediction of outcome in acute severe brain
      injury.
AB  - The purpose of this study was to evaluate prospectively short-latency
      somatosensory evoked potentials (SEPs) as a predictor of outcome in acute, severe
      brain injury, and to compare this with the predictive power of the motor
      component of the Glasgow Coma Scale score and computed tomographic scan. Outcome
      was measured with the Glasgow Outcome Scale at a minimum of 6 months after
      injury. We studied 109 patients (aged 0.1 to 16.8 years) with SEPs within 4 days
      of the onset of coma. Four patients had absent SEPs and a favorable outcome by
      the Glasgow Outcome Scale (full recovery or moderate disability); two of these
      patients had meningitis with bilateral subdural effusions, one had a midbrain
      hemorrhage, and one had a decompressive craniectomy for uncontrolled intracranial
      hypertension. Normal SEPs had a positive predictive value for favorable outcome
      of 93% (95% confidence interval (CI), 77% to 99%), and absent SEPs had a positive
      predictive value for unfavorable outcome by the Glasgow Outcome Scale (severe
      disability, survival in a persistent vegetative state, or death) of 92% (95% CI,
      80% to 98%). If the above identifiable clinical situations in which a physical
      barrier existed to impede cutaneous reception of the electrical impulse were
      excluded, the positive predictive value of absent SEPs for poor outcome reached
      100% (95% CI, 92% to 100%). An absent motor response to painful stimulus also had
      100% positive predictive value (95% CI, 84% to 100%) for unfavorable outcome;
      however, 23% of patients could not be evaluated because of the effects of muscle
      relaxants or sedatives. In patients with traumatic brain injury, results of
      computed tomography did not reliably predict outcome. Of the 59 patients with
      unfavorable outcome, 76% could be identified with SEPs compared with 36% with
      examination of motor function. We suggest that SEPs be performed in children with
      acute severe brain injury because they add an important tool to the physician's
      prognostic armamentarium. We conclude that in the absence of the above mentioned
      identifiable clinical situations, absent SEPs predict 100% unfavorable outcome,
      and this finding may warrant consideration of withdrawal of treatment in children
      with brain injuries.

PMID- 7815223
TI  - Catheter-related thrombosis in critically ill children: comparison of catheters
      with and without heparin bonding.
AB  - OBJECTIVE: To compare the incidence of and factors associated with vascular
      thrombosis after placement of heparin-bonded and standard femoral venous
      catheters. DESIGN: Prospective, masked, clinical study. SETTING:
      Multidisciplinary, tertiary, pediatric intensive care unit. PATIENTS: Consecutive
      cases (n = 50) of critically ill children admitted to a pediatric intensive care
      unit in whom either a heparin-bonded (n = 25) or a standard (n = 25) femoral
      venous catheter was placed. MEASUREMENTS AND MAIN RESULTS: Patients were examined
      by ultrasonography within 3 days of catheter insertion, weekly while the catheter
      was in place, and after catheter removal for evidence of vascular thrombosis.
      Data were collected prospectively regarding clinical evidence of catheter
      thrombosis, infusate composition, and positive blood culture results. Of 50
      patients, 13 (26%) had thrombotic complications, 11 (44%) of the 25 patients in
      the standard-catheter group, in comparison with 2 (8%) of the 25 patients in the
      heparin-bonded catheter group (p = 0.004). In addition, there was a significantly
      higher incidence of positive blood culture results among patients in the standard
      catheter group (24% vs 0%; p = 0.009). Positive catheter blood culture results
      were obtained in 38% of patients with thrombosis versus 3% without thrombosis (p
      = 0.001). Clinical evidence of thrombosis was found in 69% of patients with,
      versus 27% of patients without, ultrasound-proved thrombosis (p = 0.007).
      CONCLUSION: Heparin bonding of catheters is associated with significantly fewer
      thrombotic complications. A reduced incidence of positive catheter-related blood
      culture results may be associated with the absence of thrombosis.

PMID- 7815224
TI  - Fisher syndrome after Campylobacter jejuni enteritis: human leukocyte antigen and
      the bacterial serotype.
AB  - We describe two children who had Fisher syndrome subsequent to Campylobacter
      jejuni enteritis. The C. jejuni isolates from both patients, who lived in
      different areas, belonged to PEN 2: LIO 4. One patient had the following human
      leukocyte antigens (HLAs): HLA-A24, 33; B44, 52; DQ1; and DR2, 6 antigens.
      Another had the HLA-A24, 33; B44, 54; Cw1; DQ1, 4; and DR4, 6. An effort should
      be made to isolate C. jejuni from patients with Fisher syndrome and to perform
      HLA typing so that the pathogenesis of this syndrome can be clarified.

PMID- 7815225
TI  - Acute pancreatitis associated with acute hepatitis A in a young child.
AB  - Acute hepatitis A infection is an unusual cause of pancreatitis in adults and has
      not been reported previously in young children. We describe a 4-year-old girl
      with acute pancreatitis associated with hepatitis A infection.

PMID- 7815226
TI  - Methemoglobinemia associated with acidosis of probable renal origin.
AB  - We describe an infant who had methemoglobinemia related to acidosis, probably on
      the basis of renal tubular acidosis. Methemoglobinemia may indicate the presence
      of a clinically significant underlying disorder.

PMID- 7815228
TI  - Neonatal onset of medium-chain acyl-coenzyme A dehydrogenase deficiency with
      confusing biochemical features.
AB  - A female neonate was seen because of shock, ketosis, and undetectable blood
      glucose. Initial urinary findings indicated the possibility of a defect of fatty
      acid beta-oxidation; subsequent studies showed that she had medium-chain acyl
      coenzyme. A dehydrogenase deficiency. This case highlights the fact that the
      initial symptoms may occur in the first few days of life, and that the presence
      of ketosis does not exclude the possibility of a fatty acid oxidation defect; the
      profiles of urinary organic acids and acylglycines may not be characteristic at
      that time.

PMID- 7815227
TI  - Intact survival with transfusion-associated graft-versus-host disease proved by
      human leukocyte antigen typing of lymphocytes in skin biopsy specimens.
AB  - A transient transfusion-associated graft-versus-host disease occurred in a
      premature infant of 30 weeks of gestation. We demonstrated donor lymphocytes in a
      skin biopsy specimen with a two-step immunoperoxidase technique using monoclonal
      antibodies against human leukocyte antigen determinants specific for the donor.
      The girl survived and is immunocompetent.

PMID- 7815229
TI  - Transient organic aciduria and persistent lacticacidemia in a patient with short
      chain acyl-coenzyme A dehydrogenase deficiency.
AB  - A neonate with signs of neurologic dysfunction was noted to have elevated blood
      lactic acid levels. Organic acid analysis revealed transient elevations in
      ethylmalonate, methylsuccinate, butyrylglycine, and butyrylcarnitine. Enzyme
      assay in cultured skin fibroblasts confirmed short-chain acyl coenzyme. A
      dehydrogenase deficiency. The intermittent nature of the characteristic metabolic
      markers for this deficiency make diagnosis difficult. The apparent rarity of the
      disorder may be the result of underdiagnosis.

PMID- 7815231
TI  - Secular changes in the outcomes to eighteen to twenty-four months of age of
      extremely low birth weight infants, with adjustment for changes in risk factors
      and severity of illness.
AB  - OBJECTIVES: To analyze secular changes in the rates of death and of major
      impaired outcome in surviving outborn infants who weighted < or = 800 gm at birth
      and were admitted in 1980 to 1989, with adjustment for changes in risk factors
      and severity of illness around the time of birth; and to identify changes in
      these factors that might explain changes in outcomes. DESIGN: Retrospective
      cohort study with follow-up to a minimum of 18 months of postterm age. After
      preliminary screening, multivariate models of association between risk/severity
      of illness factors and outcomes were constructed, validated, and used to adjust
      outcomes (death and major impairment to 18 to 24 months of age). SETTING:
      Regional neonatal intensive care unit for referral of "outborn" infants.
      PATIENTS: Two hundred eighty-seven consecutively admitted infants who weighted <
      or = 800 gm at birth (97% follow-up). RESULTS: The death rate during the 1980s
      did not fall significantly (p adjusted for risk factors = 0.115). The major
      impairment rate fell (odds ratio, 0.24 (95% confidence interval, 0.10, 0.60); p =
      0.002, adjusted for delivery route and respiratory failure measures), mainly
      because of a reduced rate of blindness, not attributable to cryotherapy. The risk
      factors that improved and were possibly related to the reduced impairment rate
      were blood pH and glucose concentration, and serum sodium concentration in the
      first 48 hours of life. CONCLUSIONS: Despite an increasing selection for referral
      of less mature and more severely ill outborn babies near the "limit of
      viability," and despite more aggressive care, the rate of major impairment fell
      significantly during the 1980s. This trend was enhanced by adjustment for
      severity of illness. The fall was attributable to a reduced rate of blindness,
      and was associated with evidence of improved control of physiologic balance after
      birth.

PMID- 7815230
TI  - Congenital lacticacidemia caused by lipoamide dehydrogenase deficiency with
      favorable outcome.
AB  - A 5-year-old boy had recurrent vomiting and lethargy with lacticacidemia and
      ketoacidemia since birth. Lipoamide dehydrogenase deficiency was found in muscle
      and fibroblasts. Therapy with sodium dichloroacetate, thiamine, and carnitine was
      associated with reduction of the severity and frequency of the decompensation
      episodes and near normal plasma lactate levels. At 5 years of age, the patient
      has normal cognitive function and moderate motor impairment.

PMID- 7815232
TI  - Acuity scores as predictors of cost-related outcomes of neonatal intensive care.
AB  - OBJECTIVE: The Medicus Patient Classification System (PCS) and the lameter Acuity
      Index Method (AIM) are two proprietary scoring systems in common use for
      stratifying patient populations before making comparisons of the medical care
      they receive. In this study the validities of these scores were tested when the
      scores were used to evaluate cost-related elements of high-risk neonatal
      intensive care. METHODS: A total of 687 surviving inborn infants cared for in a
      university hospital newborn intensive care unit provided data for these analyses.
      The infants were stratified into the five diagnosis-related groups (DRGs) for
      surviving neonates (386, 387, 388, 389, and 390), as determined from their
      discharge diagnoses. Each infant's summed total of daily PCS scores, a single AIM
      score, and birth weight were extracted from the hospital's decision-support data
      files and used as independent variables in regression analyses to determine
      correlations with lengths of hospital stay, ancillary resource utilizations, and
      hospital charges. RESULTS: The Medicus scores, which are computed prospectively
      on a daily basis, when summed retrospectively, correlated highly with lengths of
      stay, ancillary resource utilization, and associated hospital charges. The
      lameter scores, which are assigned retrospectively, were far less predictive of
      these outcome variables and generally worse than birth weight in explaining
      outcome variances. CONCLUSIONS: Although in common use, the lameter AIM could not
      be validated as an appropriate method for assessing cost-related outcomes after
      newborn intensive care. The Medicus PCS produced daily scores that, when summed
      after patient discharge, correlated highly with the same outcome variables. There
      is a need to test further these and other proprietary methods now used to compare
      the cost-related elements of care provided by different hospitals and physicians.

PMID- 7815233
TI  - Synthetic surfactant for rescue treatment of respiratory distress syndrome in
      premature infants weighing from 700 to 1350 grams: impact on hospital resource
      use and charges.
AB  - To determine the impact of the use of synthetic surfactant on hospital resource
      use and charges, we analyzed the economic data from a multicenter, randomized,
      placebo-controlled clinical trial of synthetic surfactant in infants with
      neonatal respiratory distress syndrome and birth weights between 700 and 1350 gm.
      Two 5 ml/kg doses of a synthetic surfactant (Exosurf Neonatal) or air placebo
      were administered to 419 infants who were receiving mechanical ventilation and
      had an arterial/alveolar oxygen tension ratio < 0.22. In addition to the clinical
      endpoints for safety and efficacy, data were collected on length of hospital
      stay, days in the neonatal intensive care unit, days of mechanical ventilation,
      days of oxygen supplementation, and hospital charges until the infant reached 1
      year adjusted age. Growth and development of infants who received synthetic
      surfactant therapy in the study and survived to 1 year adjusted age were
      equivalent to those of the survivors in the air placebo group. For 1-year
      survivors, synthetic surfactant reduced the average length of stay at the
      different levels of care needed during the hospitalization such as neonatal
      intensive care unit days, days of mechanical ventilation, and days of oxygen
      supplementation. For nonsurvivors, synthetic surfactant increased the average
      length of stay, especially at more intense levels of care. Total hospital charges
      for the initial hospitalization and through 1 year adjusted age for a hypothetic
      cohort of 100 infants treated with synthetic surfactant were, on average, the
      same as those for a comparable cohort of infants in the air placebo group. These
      results indicate that rescue therapy with synthetic surfactant in infants with
      respiratory distress syndrome and birth weights from 700 to 1350 gm can result in
      significantly improved survival without significant increases in hospital
      charges.

PMID- 7815234
TI  - "4+ normal flora" (or is it?)

PMID- 7815235
TI  - The nutritional management of acute diarrhea in young infants.

PMID- 7815236
TI  - Clinical studies of mineral metabolism in children using stable isotopes.

PMID- 7815237
TI  - A prospective study of Shiga-like toxin-associated diarrhea in a pediatric
      population.
AB  - Although population-based studies have shown that children have the highest age
      specific incidence of infection with the Shiga-like toxin-producing E. coli
      (SLTEC), these sporadic case series were not focused specifically on the
      pediatric age group. We undertook a prospective study to determine the frequency
      of detection of SLT in an exclusively pediatric population. The study design
      minimized ascertainment and referral bias by systematically defining the
      population by the presence of diarrheal symptoms rather than by specific
      diagnosis, previous submission of stool for culture, or referral to a diarrhea
      study. All children < 10 years of age hospitalized at a tertiary care pediatric
      hospital, irrespective of admission diagnosis, were surveyed prospectively at
      admission and for 2 days thereafter for the presence of defined diarrheal
      symptoms. From May 1, 1991, to April 30, 1992, 227 patients and 92 age- and
      season-matched controls were enrolled. Fecal SLT was detected in six (2.6%)
      patients, three of whom had E. coli O157:H7 organisms were isolated; SLT was not
      found in any of the controls. SLT was more commonly detected in children 2-10
      years of age and in bloody stools. Salmonella was isolated in six (2.6%) cases,
      Shigella in five (2.2%), and Yersinia in three (1.3%); rotavirus was detected in
      46 (20.3%). Two patients with SLT-associated diarrhea had hemolytic uremic
      syndrome (HUS), and four had hemorrhagic colitis. SLT-associated diarrhea
      occurred in the summer and fall months in contradistinction to that with
      rotavirus, which occurred in the winter and spring.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7815239
TI  - Exclusive whole protein enteral diet versus prednisolone in the treatment of
      acute Crohn's disease in children.
AB  - Nineteen children with either newly diagnosed or relapsed Crohn's disease were
      enrolled in a randomized study in which the efficacy of enteral feeding with a
      whole protein-based formula was compared to high-dose corticosteroids in
      achieving clinical remission and normalization of laboratory measurements. Ten
      children were treated by enteral feeding (Nutrison Standard, Nutricia), and nine
      received corticosteroids. Both treatment regimens lasted 11 weeks. The activity
      of Crohn's disease was similar in both groups before the commencement of the
      treatment. Clinical symptoms and signs, as judged by the pediatric Crohn's
      disease activity index and measurements relating to inflammatory activity
      (erythrocyte sedimentation rate, C-reactive protein, blood leukocyte and platelet
      count, and serum immunoglobulins G and A) and to nutritional status
      (concentrations of serum albumin, prealbumin, hemoglobin) improved rapidly and
      significantly with as little as 2 weeks' treatment in both treatment groups. In
      both groups, there was one relapse within 8 weeks after discontinuation of
      treatment, and one patient in both groups was operated on during the treatment
      period. During the routine follow-up after the trial (0.3-2.5 years; mean, 1.3
      years) five of the corticosteroid group experienced a clinical relapse, whereas
      only one from the enteral feeding group relapsed. No side effects of enteral
      feeding were seen. Enteral feeding with a whole protein-based formula proved to
      be as effective as high-dose corticosteroid in the treatment of the acute phase
      of Crohn's disease and may prove to be the treatment of choice in pediatric
      patients with acute Crohn's disease.

PMID- 7815238
TI  - The nutritional management of acute diarrhea in young infants: effect of
      carbohydrate ingested.
AB  - To compare the efficacy of a low-lactose hydrolyzed milk formula, a lactose-free
      corn syrup-based milk formula, and a standard lactose-containing formula during
      refeeding after rehydration in infants with gastroenteritis, 135 patients older
      than 2 years were studied by randomized trial. Clearly demonstrated disadvantages
      in terms of early weight loss and longer duration of diarrhea were observed with
      the lactose-based formula compared with early weight gains on both the low
      lactose formulae, and thus the lactose-containing formula was discontinued after
      91 patients. The early weight loss with the lactose-containing formula was
      statistically significantly related to the degree of relative (rehydrated)
      underweight. The two low-lactose formulae were further compared in the remaining
      44 patients. Early weight gain (48 h) was significantly greater with the lactose
      hydrolyzed formula compared with the corn syrup-based formula, but no
      statistically significant differences were observed in duration of diarrhea,
      energy intake, treatment failures, or late weight gain. We conclude that the
      routine use of a low-lactose formula during refeeding after rehydration in
      infants with gastroenteritis may have some advantages in underweight infants and
      toddlers in whom it is important to prevent further weight loss.

PMID- 7815240
TI  - Prospective evaluation of upper gastrointestinal mucosal lesions in children with
      ulcerative colitis and Crohn's disease.
AB  - Eighty-eight consecutive children with inflammatory bowel disease were studied,
      and upper gastrointestinal endoscopy was performed in 80 of them as one of the
      initial investigations before commencing medical or nutritional treatment. Forty
      one children were found to have Crohn's disease and 47, ulcerative colitis. Upper
      gastrointestinal endoscopy revealed pathology in 32 (80%) cases of Crohn's
      disease, esophagitis in 16, and esophageal ulcer in two, nonspecific gastritis in
      22, duodenitis or duodenal ulcer in 18, and Helicobacter pylori infection in two
      cases. Granulomas were detected in 10 patients in the upper gastrointestinal
      tract: one esophageal, eight gastric, and three duodenal. Of the ulcerative
      colitis patients, seven had esophagitis, one had esophageal ulcer, 17 had
      nonspecific gastritis, two had gastric ulcers, two had duodenal ulcers, and five
      had H. pylori infection; altogether 30 (75%) yielded pathological findings.
      Radiological studies using barium meal revealed pathology in only eight of all
      inflammatory bowel disease cases. Symptoms at admission were not conclusive for
      definite diagnosis because 63% of patients with Crohn's disease had signs of
      colitis (such as diarrhea, bloody diarrhea) compared to 94% of ulcerative colitis
      patients. Upper gastrointestinal endoscopy may be used to achieve a specific
      diagnosis, thus being helpful when planning treatment. Also a considerable
      incidence of nonspecific gastritis, duodenitis, and esophagitis with or without
      concomitant H. pylori infection may be anticipated in children suffering from
      both ulcerative colitis and Crohn's disease.

PMID- 7815241
TI  - Bradycardia and gastroesophageal reflux in term and preterm infants: is there any
      relation?
AB  - Conflicting data are published regarding the influence of acid gastroesophageal
      reflux on the heart rate. In this study, heart rate was monitored simultaneously
      with esophageal pH in 50 infants with symptoms suggestive of gastroesophageal
      reflux disease (frequent vomiting and regurgitations). The data of 25 preterm
      infants (born at 28-36 6/7 weeks) were compared to those of 25 term infants (born
      after 37 weeks of gestation). However, both groups were investigated at identical
      postconceptional age of 47-49 weeks. Not one significant bradycardia (heart rate
      < or = 80/min during > or = 10 s) was recorded, although 71 "relative bradycardia
      episodes" (heart rate < or = 80/min during > or = 5 beats) were detected, none
      lasting for > 5 s. Although the number of infants with relative bradycardia
      episodes did not differ between groups, the relative bradycardia episodes
      occurred more frequently in some preterm infants (53 episodes in preterm infants
      vs. 18 in term babies). Acid gastroesophageal reflux episodes were observed in 46
      infants (92%). Neither the number of reflux episodes nor their duration was
      different in both groups. Simultaneous relative bradycardia episodes and acid
      reflux episodes were observed in three of 23 preterm and two of 23 term infants
      (NS). It is concluded that in a population of preterm and term infants with
      symptoms suggestive of a moderate gastroesophageal reflux pathology, investigated
      at comparable postconceptional age, most reflux episodes are not time-related to
      changes in heart rate.

PMID- 7815242
TI  - Comparison of weight-based dosages of enteric-coated microtablet enzyme
      preparations in patients with cystic fibrosis.
AB  - Twenty-one stable hospitalized cystic fibrosis patients with malabsorption
      syndrome participated in an open-label crossover clinical trial to evaluate the
      efficacy of two-period dosing regimens of a pancreatic microtablet enzyme
      preparation in the treatment of steatorrhea. Standard dosing consisted of 500 U
      lipase/kg body weight/meal, 250 U lipase/kg body weight/snack; high dosing
      consisted of 1,500 U lipase/kg body weight/meal, 750 U lipase/kg body
      weight/snack. Doses were determined by units of lipase/kg body weight to provide
      dosing consistency among patients of varying size. Each patient was on a regular
      diet of approximately 100 g of fat per day. Two separate, 72-h stool collections
      were performed between markers. A significant difference in mean percentage fat
      absorbed between the standard dose and the high dose was found (86% versus 91%, p
      < 0.05). Subjects were then stratified into two groups, based on the grams of
      fecal fat eliminated (GFFE) as follows: Group 1 with < or = 7 GFFE/24 h on both
      dosages (n = 7) and Group 2 with > 7 GFFE/24 h on either dose (n = 14). A
      significant difference (p < 0.05) between Group 1 (96%) and Group 2 (88%) was
      noted in the percentage fat absorbed while on the high dose. Fat absorption
      improved from 81% to 88%, (p < 0.05) in Group 2. During the study period, the
      adverse reactions of constipation or elevated serum uric acid levels were not
      observed. The increased doses of pancreatic enzymes resulted in improved
      correction of steatorrhea.

PMID- 7815243
TI  - Effect of a medium dose of ursodeoxycholic acid with or without taurine
      supplementation on the nutritional status of patients with cystic fibrosis: a
      randomized, placebo-controlled, crossover trial.
AB  - Ursodeoxycholic acid administration has been reported to improve cholestasis and
      inflammatory activity in primary biliary cirrhosis and, in an uncontrolled study,
      also in young adults with cystic fibrosis (CF) and chronic cholestasis. As an
      improvement in nutritional status was also observed in these young adult
      patients, we investigated whether the administration of a medium dose of
      ursodeoxycholic acid ameliorates the nutritional status of malnourished young
      adult CF patients with chronic liver disease. The study included 51 patients (27
      male patients and 24 female patients; age range, 8-32 years; median, 14) with
      body mass percentiles < 90%. Patients were randomly assigned to receive either
      ursodeoxycholic acid (10-12 mg/kg/day) alone or with taurine (18-22 mg/kg/day).
      Patients were followed in a crossover fashion within each group; 6 months of
      treatment was randomly alternated with 6 months of placebo. Nine patients dropped
      out before concluding the study. Liver function tests, nutritional status, and
      coefficients of fat absorption were determined at entry and after each 6 months
      of placebo or treatment. Nutritional status and fat absorption were not
      significantly modified by either treatment. Liver function tests improved after
      ursodeoxycholic acid administration only in patients with concomitant chronic
      liver disease. Our findings indicate that 6 months of therapy with a medium dose
      of ursodeoxycholic acid, either alone or with taurine, does not improve the
      nutritional status of young malnourished CF patients. Higher doses given for
      longer periods might be worth investigating.

PMID- 7815244
TI  - Selenium and glutathione peroxidase status in paediatric health and
      gastrointestinal disease.
AB  - To examine the effect of paediatric GI disease on selenium concentration in
      plasma and glutathione peroxidase activity in plasma and red cells, results in
      children with Crohn's disease (n = 39), cystic fibrosis (n = 14), intractable
      diarrhoea (n = 13), and biliary atresia (n = 10) were compared with those from 86
      healthy children undergoing routine operations. In Crohn's disease, plasma
      selenium concentrations were rarely low, but glutathione peroxidase activity was
      increased in the plasma and reduced in the red cells. Selenium concentration and
      glutathione peroxidase activity increased with steroid treatment but decreased
      with a selenium-deficient elemental diet. Plasma selenium concentration was
      normal in children with cystic fibrosis but very low in severely malnourished
      children with biliary atresia and intractable diarrhoea. Selenium concentration
      and glutathione peroxidase activity should be monitored in children with severe
      malnutrition or requiring prolonged nutritional support. Supplementation is
      recommended in cases of severe selenium depletion.

PMID- 7815245
TI  - Low bone mineral content and high serum osteocalcin and 1,25-dihydroxyvitamin D
      in summer- versus winter-born newborn infants: an early fetal effect?
AB  - Seasonal differences in bone mineral indices have not been studied in newborn
      infants. In adults, indicators of bone metabolism may show seasonal variations.
      In postneonatal infants and possibly in adults, vitamin D metabolism shows
      seasonal variations. We hypothesized that in winter-born infants, the bone
      mineral content is low and serum osteocalcin is high, related to increased bone
      turnover and high serum 1,25-dihydroxyvitamin D [1,25(OH)2D]. We studied 246
      healthy, term appropriate-for-gestation infants in winter (January through March;
      140 children) and summer (July through September; 106 children). The bone mineral
      content (BMC) of the one-third distal radius was measured before 3 days of age by
      photon absorptiometry. Significant seasonal differences were found: summer-born
      infants had significantly lower BMC, higher serum osteocalcin and 1,25(OH)2D, and
      lower serum total calcium than winter-born infants. Seasonal differences in BMC
      remained significant after adjusting for race and sex. BMC was not correlated
      with serum biochemical measures. Thus, summer-born newborn infants have low BMC
      and high serum osteocalcin and 1,25(OH)2D than winter-born infants; these
      findings are the opposite of adult findings. We suggest that seasonal effects on
      fetal bone operate especially in early pregnancy (approximately 6 months before
      birth) resulting in a "phase effect" and opposite findings from later life.

PMID- 7815246
TI  - Reduction in virus-neutralizing activity of a bovine colostrum immunoglobulin
      concentrate by gastric acid and digestive enzymes.
AB  - Bovine milk immunoglobulin concentrates have been proposed for inducing passive
      immunity against various enteric pathogens. In vitro digestion studies were
      conducted to evaluate the effect of gastrointestinal secretions on the virus
      neutralizing activity of a concentrate prepared from the colostrum of cows that
      were immunized with rotavirus. The proteolytic activity of human gastric and
      duodenal fluid specimens was used to design a two-stage in vitro digestion model
      with commercial enzymes for estimating the individual impact of pepsin, gastric
      acid, and select pancreatic enzymes on antirotavirus activity in bovine milk
      immunoglobulin concentrates. The rotavirus-neutralizing titer of concentrate was
      decreased by incubation with pepsin at pH 2, a pool of pancreatic enzymes at pH
      7.5, or sequential digestion with pepsin (pH 2) and pancreatic enzymes (from
      initial titer of 55,210 to 2,030, 19,500, and 320, respectively). Reduction in
      rotavirus-neutralizing titer after gastric-phase digestion was primarily due to
      acidic conditions and not to proteolytic cleavage by pepsin. Although both
      trypsin and carboxypeptidase caused significant proteolysis of concentrate during
      duodenal-phase digestion, only trypsin caused a significant reduction in
      rotavirus-neutralizing titer. The extent of digestion was the same for
      concentrate suspended in water or skim milk. The results demonstrate that the
      biological activity of bovine milk antibodies is reduced by exposure to acid and
      trypsin in vitro and suggest that neutralization of both gastric acid and
      pancreatic trypsin may enhance the effectiveness and economic feasibility of
      passive oral immunoprophylaxis with bovine milk immunoglobulins.

PMID- 7815247
TI  - Platelet-activating factor acetylhydrolase in term and preterm human milk: a
      preliminary report.
AB  - Human milk may protect against necrotizing enterocolitis (NEC). Since platelet
      activating factor (PAF) may participate in the pathophysiology of NEC, we
      measured PAF acetylhydrolase (PAF-AH), which metabolizes PAF, in term and preterm
      human milk. The activity of PAF-AH in term milk collected 2-4 days after delivery
      (n = 17) was 2.7 +/- 1.2 nmol x min-1 x ml-1. A higher activity was found in milk
      collected at similar times from mothers who delivered between 33 and 36 weeks of
      gestation (n = 6, 5.6 +/- 2.1 nmol x min-1 x ml-1, p < 0.01). However, milk from
      mothers who delivered between 26 and 32 weeks of gestation had a PAF-AH activity
      similar to that of term milk (n = 6, 3.0 +/- 0.7 nmol x min-1 x ml-1). With
      advancing lactational age, PAF-AH activity in term milk decreased, whereas the
      activity of this enzyme in preterm milk remained unchanged. In milk samples
      collected beyond 14 days after delivery from women who gave birth between 33 and
      36 weeks or 26 and 32 weeks of gestation, PAF-AH activity was fivefold higher
      than that found in milk for women delivering at term (3.7 +/- 1.3 and 3.6 +/- 3.6
      nmol x min-1 x ml-1 serum 0.7 +/- 0.4 nmol x min-1 x ml-1, respectively, p <
      0.05). We speculate that the presence of PAF-AH in human milk may protect against
      NEC in preterm newborns.

PMID- 7815248
TI  - Chicken-induced anaphylactoid reaction and colitis.

PMID- 7815249
TI  - Potentiation of acetaminophen hepatotoxicity in a child with mercury poisoning.

PMID- 7815250
TI  - Short-gut syndrome: intestinal adaptation in a patient with 12 cm of jejunum.

PMID- 7815251
TI  - Activated T cells and genetic restriction in celiac disease.

PMID- 7815252
TI  - Earth, wind, and fiber: is there a drug to treat acute diarrhea?

PMID- 7815254
TI  - Screening test for galactosemia.

PMID- 7815253
TI  - Neonatal Dubin-Johnson syndrome.

PMID- 7815255
TI  - Committee report: childhood diet and prevention of coronary heart disease. ESPGAN
      Committee on Nutrition. European Society of Pediatric Gastroenterology and
      Nutrition.
AB  - Coronary heart disease is a major cause of morbidity and mortality in Europe,
      particularly northern, central, and eastern Europe. Several strategies have been
      recommended for children and adolescents to promote a healthy lifestyle and
      thereby reduce the risk of coronary heart disease in later life. The European
      Society of Pediatric Gastroenterology and Nutrition (ESPGAN) Committee on
      Nutrition reviewed some of these strategies, and our conclusions and
      recommendations are reported herein.

PMID- 7815256
TI  - Do H2 receptor antagonists have a therapeutic role in childhood?
AB  - Studies of the therapeutic efficacy and indications for the use of histamine (H2)
      receptor antagonists (H2RAs) in children are reviewed. In adequate dosages, both
      ranitidine and cimetidine reduce acid output and increase intragastric pH, and
      H2RAs have been shown to be effective in the treatment of acid-peptic disease.
      Ranitidine is a more potent drug with a longer duration of action than cimetidine
      and thus requires less frequent administration. Dosage requirements vary
      according to age and clinical condition, and children require a relatively higher
      drug dosage (mg/kg) than adults. There is insufficient information on the long
      term paediatric use of famotidine to validate its use in children, and the
      endocrinological side effects associated with cimetidine therapy in adults
      essentially preclude its long-term use in children. It is suggested that
      ranitidine administration is safe and effective in children with acid-peptic
      disease and should be considered as first-line treatment for children with severe
      oesophagitis or peptic ulceration and for the prophylaxis of stress ulceration
      and aspiration pneumonitis.

PMID- 7815257
TI  - The interobserver reproducibility of bioelectrical impedance analysis
      measurements in infants and toddlers.
AB  - Although nomograms to convert readings of resistance (R) and reactance (Xc) into
      estimates of body composition have begun to emerge for children as well as
      adults, there has been reluctance to use bioelectrical impedance analysis (BIA)
      in very young children due to the irritability of children, measurement
      instability, positioning of electrodes, and, of course, reproducibility of
      measurements. The precision of completely independent measurements of BIA indices
      was evaluated by two observers by comparing a series of 40 measurements of R and
      Xc and 36 measurements for weight in four malnourished children on 10 different
      days during the course of their nutritional recuperation. For weight, the CV
      (coefficient of variation) was 3.5% for observer A and 3.8% for observer B. There
      were no differences in the means across observers with respect to weight, R, and
      Xc. The results obtained in this study illustrate that properly trained observers
      following the same standards can produce equivalent data for BIA and weight
      measurements even in sick children.

PMID- 7815258
TI  - Successful pancolonoscopy and ileoscopy in children.
AB  - The purpose of this study was to collect prospective data regarding the quality,
      extent, and duration of pediatric pancolonoscopy performed by pediatric
      gastroenterology attending physicians and a fellow in training. Over 7 months,
      data were prospectively collected on 40 colonoscopic procedures. The cecum was
      reached in 37 cases (92.5%) and the terminal ileum in 35 cases (87.5%). When
      cases of stricture and equipment failure were excluded, these completion rates
      were 97 and 95%, respectively. The overall average duration for pancolonoscopy,
      ileoscopy, multiple biopsies, and polypectomy (where necessary) was 38 min. When
      attending physicians performed the procedure, the duration was 31 min; the
      duration was 37 min when the fellow completed the procedure and 45 min when the
      fellow required the attending physician to complete it. The average time taken to
      reach the cecum by the attending physician was 19 min (range, 8-32); by the
      fellow it was 25 min (range, 17-32), and by the combination it was 37 min (range,
      11-59). The average time from cecum to terminal ileum was 3 min for all, with
      ranges of 1-12 min for the attending physician and 1-23 min for the fellow. The
      fellow initiated 24 procedures, of which the attending physician was required to
      complete 12, including all five procedures performed in the initial 2 months of
      the study, 7 of 13 in the next 3 months, and none of the six procedures in the
      last 2 months. Of the 40 examinations, the colon was normal in five (12.5%), and
      a specific diagnosis was made in 35.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7815259
TI  - Cyclosporine as an alternative to surgery in children with inflammatory bowel
      disease.
AB  - Five children with ulcerative colitis for whom surgery was recommended were
      treated with cyclosporine. The five had received corticosteroids for 1-24 months.
      The group included two patients with acute-onset ulcerative colitis and three
      with acute exacerbations of intractable corticosteroid-dependent chronic
      ulcerative colitis. The average age at initiation of cyclosporine therapy was
      13.8 years (range, 11.5-16); all five patients were boys. Cyclosporine was
      initiated in the hospital by continuous i.v. infusion. Trough levels of 400-600
      ng/dl (measured by radioimmunoassay) were achieved, at which point oral
      cyclosporine was given and oral dosage was adjusted to similar levels.
      Significant hypertension requiring medical attention was seen in one patient. Of
      the two recently diagnosed acute cases, one failed to respond and required
      subtotal colectomy after 2 weeks of treatment, and the other, despite an initial
      response, had a subtotal colectomy 10 months later. Of the three corticosteroid
      dependent children, none was able to be weaned from corticosteroids and all
      underwent subtotal colectomy. Our experience emphasizes that the appropriate role
      of cyclosporine as therapy for children with ulcerative colitis is yet to be
      determined. Cyclosporine was not effective as an alternative to surgery in our
      patients.

PMID- 7815260
TI  - Intensive nutritional support and remedial surgical intervention for extreme
      short bowel syndrome.
AB  - Management of extreme short bowel syndrome (SBS) has changed dramatically over
      the last 20 years with notable improvements in survival and quality of life in
      patients with this syndrome. A review of our institution's medical records over a
      12-year period (1980-1992) revealed 32 patients with < 100 cm (range, 14-94;
      median, 40) of functional small bowel after intestinal resection. The causes of
      intestinal loss included necrotizing enterocolitis (11 cases), atresias (8
      cases), long-segment Hirschsprung's disease (5 cases), midgut volvulus (5 cases)
      and gastroschisis (3 cases). The mean follow-up period was 4.2 years, and four
      deaths were recorded (12.5%). Survival of eight of nine (88.9%) patients without
      an ileocecal valve (ICV) and with < 40 cm of small bowel was noted. The absence
      of an ICV, however, was associated with significantly prolonged total parenteral
      nutrition. Follow-up surgical procedures, including intestinal lengthening,
      tapering enteroplasty. Martin's procedure, longitudinal myectomy-myotomy, and
      ostomy take-down, were performed in 20 of the patients (64%). Prolonged survival
      and normal development can be expected for the patient with severe SBS who is
      given meticulous nutritional support and treated with carefully planned secondary
      surgical intervention. These results are also seen in patients with extreme SBS
      (< 40 cm residual small bowel length) and no ICV.

PMID- 7815261
TI  - The acid steatocrit: a much improved method.
AB  - The steatocrit method has recently been introduced as a simple screening test for
      steatorrhea. As it seemed likely that separation of fecal homogenate by
      centrifugation into a lipid phase, a watery phase, and a solid phase would be pH
      dependent, we evaluated the effect of fecal acidification on steatocrit results.
      We also compared classical and acid steatocrit results in healthy children and in
      patients with cystic fibrosis and studied the relationship between two steatocrit
      methods and fecal fat content as measured by a reference chemical method.
      Steatocrit results increased with the degree of fecal acidification, and maximal
      results were obtained at the lowest fecal pH values. Means and SEM for classical
      and acid steatocrit values were 1.1 +/- 0.4% (classical) versus 3.8 +/- 1% (acid)
      in controls (n = 6) and 5.4 +/- 1.9% (classical) versus 26.9 +/- 4.3% (acid) in
      cystic fibrosis patients (n = 9). The correlations between fecal fat content
      measured chemically and steatocrit results were 0.18 (p = 0.35) and 0.81 (p <
      0.0001) for classical and acid steatocrit, respectively. We conclude that
      acidification of fecal homogenates leads to a marked improvement in the
      steatocrit method.

PMID- 7815262
TI  - Use of serological markers as a screening test in family members of patients with
      celiac disease.
AB  - That symptomatic celiac disease (CD) can occur in several members of a family has
      long been recognized. Given the possible complications of untreated CD, it is
      also important to diagnose those family members with "silent" disease, to offer
      them the benefit of a gluten-free diet. We studied 642 first-degree relatives of
      210 patients with CD, two of the latter belonging to the same family. IgA and IgG
      antigliadin antibodies and IgA antiendomysium antibodies were studied in all.
      Jejunal biopsy was performed in 59 subjects, 47 with positive and 12 with
      negative serological markers. Celiac disease was diagnosed de novo in 18 cases
      (2.8%). Diagnosis in a symptomatic mother was made by jejunal biopsy despite the
      negativity of all immunological markers. We conclude that the risk of having CD
      is higher in siblings than in parents of patients with CD, that the most useful
      marker for diagnosis is the study of IgA antiendomysium antibodies, and that the
      absence of positive serological markers does not completely exclude the diagnosis
      of CD.

PMID- 7815263
TI  - Intestinal microflora in colicky and noncolicky infants: bacterial cultures and
      gas-liquid chromatography.
AB  - To find out whether intestinal microflora in colicky infants is different from
      that in noncolicky controls, stool samples were collected from colicky infants
      during colic (n = 55) and at the age of 3 months (n = 46) and compared with
      samples from age-matched controls (n = 49 and n = 45, respectively). The samples
      were cultured on several selective and unselective aerobic and anaerobic culture
      agars, and gas-liquid chromatography of bacterial cellular fatty acids was used
      to produce fatty-acid profiles of the stool samples. In quantitative bacterial
      cultures, no differences were found between the colicky and control groups in the
      amounts of each bacterium. The colicky infants were more frequently colonized
      with Clostridium difficile during the time of colic than were the age-matched
      controls. This difference disappeared by age 3 months. The fatty-acid profiles
      did not differ between the colicky and control groups as a whole at the time of
      colicky symptoms. At age 3 months, a difference in fatty-acid profiles was found
      between the colicky infants who had suffered from severe colic and the control
      infants. The fatty-acid profiles were also influenced by the age of the infant,
      the mode of delivery, antimicrobial drugs taken by the mother during delivery,
      and breast-feeding and type of feeding. In conclusion, no difference in
      intestinal microflora was found between the colicky infants at the time of colic
      and the controls. However, a difference in bacterial cellular fatty-acid profiles
      at the age of 3 months was found that correlated with severe infantile colic.
      This difference may contribute to the cause(s) of colic, or it may be secondary
      to the colic, which may influence the microbial environment of the intestine.

PMID- 7815264
TI  - Marked gastric mucosal hyperplasia without definite peptic ulceration related to
      a multifocal hepatic gastrinoma.

PMID- 7815265
TI  - Decompression of portal hypertension in a child with cystic fibrosis after
      transjugular intrahepatic portosystemic shunt placement.

PMID- 7815266
TI  - Hyperplastic duodenal polyp in a boy.

PMID- 7815267
TI  - Evaluation of drug-containing microcapsules.
AB  - The characterization of microcapsules containing drugs is reviewed with
      particular emphasis on sustained-release products produced commercially by pan or
      air-suspension coating and intended for oral administration. After considering
      aspects of the core and coating, various technologies used to assess
      microcapsules are discussed such as optical and spectroscopic evaluation,
      particle size analysis, filling into hard gelatin capsules, and disintegration,
      dispersion and dissolution testing. The in vivo testing of microcapsules and
      correlation with in vitro data is considered. Finally some miscellaneous tests
      applied to the formation and assessment of microcapsules are presented.

PMID- 7815268
TI  - Evaluation of the properties of ethylcellulose-cellulose triacetate microcapsules
      containing theophylline prepared by different microencapsulation techniques.
AB  - Using cellulose triacetate as an added complementary coating material in
      preparing sustained-release ethylcellulose-cellulose triacetate microcapsules of
      theophylline, three microencapsulation techniques were investigated.
      Ethylcellulose-cellulose triacetate composite microcapsules, ethylcellulose
      cellulose triacetate dual-walled microcapsules and ethylcellulose microcapsules
      containing cellulose triacetate matrices were prepared using the non-solvent
      addition phase separation method. The effects of cellulose triacetate on the
      release of theophylline from the different ethylcellulose-cellulose triacetate
      microcapsules were obtained from dissolution studies. The results showed that the
      release rates of ethylcellulose-cellulose triacetate microcapsules were slower
      than those obtained from the ethylcellulose microcapsules prepared with similar
      core to wall ratios. The ethylcellulose microcapsules containing cellulose
      triacetate matrices had longer release half-times and smaller surface areas than
      the other capsule preparation. The release patterns of theophylline from the
      different ethylcellulose-cellulose triacetate microcapsules fitted first-order
      kinetics. Scanning electron micrographs showed that the surfaces of various
      ethylcellulose-cellulose triacetate microcapsules were different from those of
      theophylline, cellulose triacetate matrices of cellulose triacetate
      microcapsules, and that the surface morphology of ethylcellulose-cellulose
      triacetate microcapsules was affected by the preparative method.

PMID- 7815269
TI  - Studies on the properties of ethylcellulose microcapsules prepared by emulsion
      non-solvent addition method in the presence of non-solvent in polymer solution.
AB  - Ethylcellulose microcapsules containing theophylline were prepared by the O/W
      emulsion non-solvent addition method. Toluene-cyclohexane was chosen as a solvent
      non-solvent pair. The effect of the non-solvent added to the polymer solution on
      the properties of microcapsules was investigated. The results indicated that the
      size distribution and drug content of microcapsules were slightly affected by the
      amount of non-solvent in polymer solution. However, the internal conformation of
      microcapsules was directly related to the amount of non-solvent added to the
      polymer solution. The greater the non-solvent to solvent ratio in polymer
      solution the larger the percentage of microcapsules having a hollow conformation.
      Dissolution studies showed that the release rate of theophylline from
      microcapsules increased with increasing amount of non-solvent added to the
      polymer solution, but the release pattern of microcapsules was not obviously
      changed.

PMID- 7815270
TI  - An interpretative analysis of the effect of the surfactants used for the
      preparation of polyalkylcyanoacrylate nanoparticles on the release process.
AB  - The release of fluorescein from polyethylcyanoacrylate (PECA) or
      polyisobutylcyanoacrylate (PICA) nanoparticles was affected by the surfactants
      used for the preparation. The different surfactants also modified the molecular
      weight, size and loading of the nanoparticles. However, these factors were not be
      responsible for the different release. According to the release profiles and the
      Baker-Lonsdale model, a portion of fluorescein was concentrated near the
      nanoparticle surface. Thus, a non-homogeneous distribution of the fluorescent
      probe inside the nanoparticles was hypothesized. This distribution could reflect
      the fluorescein position inside the micella during the polymerization stage, or
      could be reached during the washing stage as the consequence of a different
      effect of the surfactants on the porosity of the nanoparticle structure.

PMID- 7815272
TI  - Preparation and characterization of ethylcellulose microspheres containing 5
      fluorouracil.
AB  - Ethylcellulose microspheres containing 5-fluorouracil (5-FU) were prepared by a
      solvent evaporation technique using light mineral oil as the continuous phase.
      The drug was suspended in the acetone solution of the polymer. Three drug/polymer
      ratios (1/1, 1/2 and 1/3) were utilized. The microspheres were studied with
      respect to size, drug content and surface characteristics; the higher the polymer
      content, the smoother the microspheres. The drug was suspended in the polymer and
      the drug loading was important (more than 90%) with the three types of
      microspheres. In vitro dissolution studies in phosphate buffer showed that the 5
      FU release was dependent on the drug/polymer ratio for the 400-500 microns
      granulometric fraction.

PMID- 7815271
TI  - A lymphotropic colloidal carrier system for diethylcarbamazine: preparation and
      performance evaluation.
AB  - Targeting to organs other than the RES-bearing organs is difficult to achieve. A
      nanoparticle-based emulsion delivery system was prepared and its efficacy in
      enhancing the lymphatic uptake of the anti-filarial drug diethylcarbamazine was
      evaluated. It was compared with a simple w/o emulsion and a control aqueous
      solution. The effect of route of administration on the lymphatic uptake was
      studied and it was found that the i.p. route gave better results as compared to
      the i.v. route, in which total lack of lymphatic uptake was observed. The
      nanoparticle-in-oil emulsion system holds excellent potential as a lymphotropic
      carrier system.

PMID- 7815273
TI  - Kinetics of bromocriptine release from microspheres: comparative analysis between
      different in vitro models.
AB  - This paper describes how the use of different in vitro experimental systems can
      influence the determination of (a) the drug release profile from microparticles
      and (b) the interpretation of the release mechanism(s). We employed, as model
      dosage form, the Parlodel LA, a recently marketed microsphere system especially
      designed for bromocriptine-controlled delivery. The release kinetics of
      bromocriptine from microspheres were determined by using two different
      experimental approaches: a dialysis method and a flow-through cell method. From
      the comparison of the obtained data it clearly appears that different in vitro
      experimental models lead to distinct results in terms of drug availability. On
      the contrary both series of data can be convincingly fitted with the same
      mathematical equation, giving almost identical results in terms of postulated
      release mechanism. Taken together these results indicate that different
      experimental approaches should always be employed to determine drug release
      kinetics from microparticles in order to obtain more reliable information on the
      therapeutic dose (bioavailable drug, for in vivo experiments) and on the
      uniformity of different batches of microspheres.

PMID- 7815274
TI  - The influence of surface properties on uptake of oil into complex coacervate
      microcapsules.
AB  - A range of surfactants with different hydrophile-lipophile balance (HLB) values
      was selected to investigate the influence of interfacial properties on the uptake
      of oil droplets into complex coacervate microcapsules. The well characterized
      gelatin/acacia complex coacervate system was used in this study and the
      encapsulation of squalane, and oleic acid was investigated. The surfactants
      investigated were Span 85, Span 80, Span 40, egg yolk lecithin, and Tween 80.
      Combinations of surfactants were utilized to obtain intermediate HLB values. The
      percentage oil encapsulated was determined gravimetrically, based on the initial
      concentration and the amount extracted from the microcapsules. The aqueous
      interfacial tension values of the oils and oil/surfactant systems were measured
      using the Wilhelmy plate method. The interfacial properties were correlated to
      the percentage oil uptake by the coacervate phase. The relative
      hydrophobicity/lipophilicity of the oil influenced its uptake by complex
      coacervate droplets. The presence of surfactant affected oil uptake, depending on
      the HLB value of the surfactant or surfactant mixture. Uptake of squalane by the
      gelatin/acacia coacervates was found to be optimized by the addition of
      surfactants with HLB values in the range 2.5-6. The percentage uptake of oil
      decreased rapidly for systems prepared containing surfactants with HLB values
      outside this range. No correlation was observed between oil uptake by the
      coacervate phase and the interfacial tension of the oil and oil/surfactant
      systems with double-distilled deionized water.

PMID- 7815275
TI  - The influence of cosolvents on the in-vitro percutaneous penetration of
      diclofenac sodium from a gel system.
AB  - The influence of cosolovents on the in-vitro percutaneous penetration of
      diclofenac sodium from a gel system was studied using a simplex lattice
      experimental design. Gel formulations were prepared by gelling the vehicle
      mixture of water, alcohol and propylene glycol with Carbomer 940. The synthetic
      membrane Durapore and hairless mouse skin were employed as barriers in a Franz
      type diffusion cell. It was found that the penetration through the synthetic
      membrane was well described by the Higuchi model. There existed a better inverse
      relationship between the penetration rate and the drug solubility in the
      respective vehicle. It appeared to be a membrane-controlled mechanism when using
      hairless mouse skin as the barrier. The penetration rates in steady-state for
      nine formulations were fitted to a polynomial equation based on this simplex
      lattice method. A three-dimensional plot was constructed in this simplex surface
      studied. The maximal penetration rate was found to be from the vehicle containing
      water and ethanol in an exact volume ratio of 3:1 and the minimal penetration
      rate was observed from the vehicle containing water only.

PMID- 7815277
TI  - Investigating the surface properties and bioadhesion of buccal patches.
AB  - By using a two-roll milling method, a new bioadhesive polymer patch formulation
      for drug controlled delivery and consisting of Carbopol 934P (CP),
      polyisobutylene (PIB), and polyisoprene (PIP) was prepared. The effects of
      different ratios of CP:PIB:PIP on the surface properties, adhesion, and swelling
      of buccal patches were investigated. It was found that the surface properties of
      buccal patches were not only dependent on the CP content but also dependent on
      the PIB:PIP ratio. The strongest peeling strength was found on the buccal patches
      with a CP:PIB:PIP ratio of 50:43.75:6.25. The maximum bioadhesion of patches was
      found following 2- to 8-h contact with the test medium, and this observation
      could be explained by the interpenetration of macromolecular chains at the
      polymer-polymer interface (based on the diffusion theory of polymer adhesion).

PMID- 7815276
TI  - Effect of topical preparation of mycophenolic acid on experimental allergic
      contact dermatitis of guinea-pigs induced by dinitrofluorobenzene.
AB  - The effects of a topical preparation of mycophenolic acid on the experimental
      allergic contact dermatitis induced by dinitrofluorobenzene was investigated.
      Visual assessment of skin reactions showed significant efficacy of a topical
      preparation of mycophenolic acid. This efficacy appeared from the early stage and
      endured up to 3 days. Morphological changes in the epidermis and dermis layers of
      animals treated with a mycophenolic acid cream were moderate compared with that
      in animals treated with vehicle only. In particular, hyperkeratosis was strongly
      suppressed. Since suppression of inflammatory cell infiltration was also
      observed, this efficacy might reach to the epidermis and dermis layer.

PMID- 7815278
TI  - Nasal absorption of desmopressin in rats and sheep. Effect of a bioadhesive
      microsphere delivery system.
AB  - The nasal absorption of desmopressin was studied in two animal models, the rat
      and the sheep. The bioavailability after nasal administration was found to be 13
      times higher in the rat model. This discrepancy is suggested to be due to the
      impaired mucociliary clearance mechanism in the rat model and possibly
      differences in enzymatic degradation and elimination rates of the drug. The
      effect of the addition of L-alpha-lysophosphatidylcholine (LPC) to the
      formulations as an absorption enhancer was most pronounced in the sheep model.
      The use of the bioadhesive starch microsphere delivery system, especially in
      combination with LPC, had a profound effect on the absorption of desmopressin in
      sheep, with bioavailabilities reaching nearly 10% compared with 1.2% for a simple
      nasal solution of desmopressin.

PMID- 7815279
TI  - The distribution of an intranasal insulin formulation in healthy volunteers:
      effect of different administration techniques.
AB  - The initial deposition pattern in the nasal passages and subsequent clearance of
      an insulin formulation labelled with 99mTc-human serum albumin have been
      determined in 12 healthy male volunteers. Four different administration modes
      from a novel aqueous spray device were compared, involving delivered volumes of
      80-160 microL, and with either gentle or vigorous inhalation while firing the
      device. The entire dose was deposited in the nasal cavity, and no significant
      radioactivity was deposited in the lungs. A mean 25-33% of the radiolabel
      remained in the nose after 4 h. A significantly smaller area of the nasal mucosa
      was covered by the smallest (80 microL) bolus, but subsequent clearance rates did
      not vary significantly with mode of administration. Blood glucose levels fell
      after administration of the insulin formulation, but no serious episodes of
      hypoglycaemia occurred.

PMID- 7815280
TI  - Anti-hypertensive effect of oral controlled-release microspheres containing an
      ACE inhibitor (delapril hydrochloride) in rats.
AB  - An oral controlled-release drug delivery system based on microspheres of
      polyglycerol esters of fatty acids (PGEFs), was applied to an anti-hypertensive,
      delapril hydrochloride. The in-vitro release profile was controlled by selecting
      a PGEF with an appropriate hydrophilic-lipophilic balance value for the matrix.
      The microspheres from which 80% of the drug was released in 6 h were orally
      administered to rats. The plasma concentration of the active metabolite was
      sustained after administration of the microspheres in comparison with
      administration of a solution. The in-vivo release profile was in good agreement
      with the in-vitro release profile. When the microspheres were administered, the
      pharmacological effect of delapril hydrochloride on the angiotensin I-induced
      pressor response was also sustained showing consistency with the plasma
      concentration-time curve.

PMID- 7815281
TI  - Constipation evoked by 5-HT3-receptor antagonism: evidence for heterogeneous
      efficacy among different antagonists in guinea-pigs.
AB  - The abilities of selective 5-HT3-receptor antagonists to evoke constipation were
      examined in conscious guinea-pigs and in preparations of guinea-pig isolated
      colon. Compared with vehicle-treated guinea-pigs, acute doses of granisetron
      (0.1, 1 and 10 mg kg-1, i.p.) and tropisetron (10 mg kg-1, i.p., but not 1 and
      0.1 mg kg-1, i.p.) significantly (P < 0.05) reduced the total number of faecal
      pellets excreted during a 12-h observation period. By contrast, BRL 46470 (0.1-10
      mg kg-1, i.p.) had no significant effect on the incidence of defecation. Mid-to
      distal lengths of guinea-pig isolated colon spontaneously expelled faecal
      pellets. Granisetron (0.1 and 1 microM) and tropisetron (1 microM) reduced or
      prevented the rate at which they were spontaneously expelled. Morphine (0.1
      microM) and clonidine (10 nM) also showed faecal pellet transit time. Naloxone
      (0.1 microM) had no effects alone, but reversed the actions of granisetron,
      morphine and clonidine. BRL 46470 (1 microM) had no significant effect on the
      transit of faecal pellets in guinea-pig isolated colon. In segments of guinea-pig
      isolated colon which did not contain faecal pellets, granisetron, tropisetron and
      BRL 46470 antagonized the ability of 5-HT to evoke cholinergically-mediated
      contractions of the longitudinal muscle. The respective pA2 values and slopes of
      the Schild plots were 8.5 +/- 0.05, slope 1.06 +/- 0.03; 8.5 +/- 0.1, slope 0.91
      +/- 0.04; and 7.9 +/- 0.1, slope 0.93 +/- 0.05. Our experiments suggest that not
      all 5-HT3-receptor antagonists are the same.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7815282
TI  - Subcellular distribution of proteolytic activities degrading bioactive peptides
      and analogues in the rat small intestinal and colonic enterocytes.
AB  - The objective of this study was to compare, in rat small intestinal and colonic
      enterocytes, subcellular distributions of activities degrading the large
      peptides, neurotensin, acetylneurotensin (8-13), GRF(1-29)NH2 (human growth
      hormone releasing factor fragment), (desNH2Tyr1,D-Ala2,Ala15)-GRF(1-29)NH2,
      insulin, and insulin B-chain. Proteolytic activities degrading individual
      peptides in the 10,000-g pellet, rich in intracellular organelles, 27,000-g
      pellet, rich in brush-border membrane, 100,000-g pellet, and 100,000-g
      supernatant, rich in cytosol, were determined and compared for both the small
      intestine and colon. In colonic fractions, the cytosol had highest activity (g
      protein)-1 degrading three out of four peptides tested, while in small intestinal
      fractions, the 27,000-g pellet had the highest activity (g protein)-1, degrading
      four out of five peptides tested. In both small intestine and colon, the cytosol
      had a higher percentage of total proteolytic activity degrading each of the above
      polypeptides and the highest insulin-degrading activity (g protein)-1. The
      results suggest that at pH 7.5, proteolytic activities (g protein)-1 in the
      fraction of subcellular organelles are much lower than those in cytosol and that
      cytosolic proteolytic activities degrading polypeptides and analogues are
      significant.

PMID- 7815283
TI  - The stimulative effect of diffusion potential on enoxacin uptake across rat
      intestinal brush-border membranes.
AB  - Evidence of a membrane potential dependence for enoxacin uptake by rat intestinal
      brush-border membrane vesicles has been found. The transient overshooting uptake
      of enoxacin disappeared in the voltage-clamped brush-border membrane vesicles in
      the presence of an outward H(+)-gradient. Momentary dissipation of the H(+)
      gradient itself by carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone (FCCP)
      did not affect the uptake of enoxacin. In contrast, enoxacin uptake was depressed
      by an interior positive K(+)-diffusion potential induced by valinomycin.
      Furthermore, not only the outward H(+)-gradient but also an inward Cl(-)-gradient
      caused a stimulating effect on enoxacin uptake, and the stimulation by the Cl(-)
      gradient was dissipated by using voltage-clamped membrane vesicles. These results
      indicate that enoxacin transportation across the brush-border membrane is
      dependent on the ionic diffusion potential. On the other hand, neither Gly-Gly
      nor guanidine had any effect on enoxacin uptake by the membrane vesicles in the
      presence of an inward (for Gly-Gly) or outward (for guanidine) H(+)-gradient as a
      driving force for each transport system. Therefore, it seems that enoxacin
      transport through the intestinal epithelia does not participate in the carrier
      mediated transport systems for Gly-Gly and guanidine.

PMID- 7815284
TI  - The inhibitory effects of cephalosporin and dipeptide on ceftibuten uptake by
      human and rat intestinal brush-border membrane vesicles.
AB  - The types of inhibitory effects caused by compound V (an analogue of ceftibuten)
      and alanylproline (dipeptide) on the uptake of ceftibuten by brush-border
      membrane vesicles (BBMV) prepared from human and rat small intestine were
      analysed. In the presence of an inward H(+)-gradient, the initial uptake rate of
      ceftibuten by both human and rat intestinal BBMV was concentration-dependent with
      apparent Km and Vmax values of 0.35 mM and 2.052 nmol (mg protein)-1 min-1 for
      human BBMV, and 0.50 mM and 3.056 nmol (mg protein)-1 min-1 for rat BBMV,
      respectively. For both human and rat BBMV, kinetic analysis by Dixon and
      Lineweaver-Burk plots demonstrated that the uptake of ceftibuten was
      competitively inhibited by compound V, whereas inhibition by alanylproline was
      noncompetitive or partially competitive. These results suggest that there is a
      stereospecific transport system which is common to ceftibuten and compound V, and
      that this system is not identical to the carrier system for the dipeptide,
      alanylproline.

PMID- 7815285
TI  - Pharmacokinetic characteristics of 5-fluorouracil and mitomycin C in
      intraperitoneal chemotherapy.
AB  - Eight patients with malignancies confined to the peritoneal space participated in
      this study. Five hundred milligrams 5-fluorouracil or 10 mg mitomycin C was
      diluted in 1 L saline. The mixed solution was injected intraperitoneally through
      the semi-permanent peritoneal catheter. Blood and peritoneal fluid were collected
      after injection. 5-Fluorouracil concentrations in the peritoneal fluid were 1000
      times those in serum, while mitomycin C concentrations were 100 times those in
      serum. Areas under the concentration vs time curve (AUC) were calculated by the
      trapezoidal method with extrapolation to infinity. The ratio of peritoneal fluid
      AUC to serum AUC was about 1400 for 5-fluorouracil and 80 for mitomycin C.
      Patterns for the absorption and elimination from systemic circulation were
      similar for both compounds. Drug concentrations in the peritoneal fluid and serum
      were analysed according to the compartment model. The half-life in the peritoneal
      fluid (t1/2p) and the rate constant from the peritoneal fluid to the systemic
      circulation (ka) were nearly equal for both 5-fluorouracil and mitomycin C
      (t1/2p, 1.0 h for 5-fluorouracil and 1.3 h for mitomycin C; ka 0.71 h-1 for 5
      fluorouracil and 0.68 h-1 for mitomycin C), although the apparent volume of
      distribution (Vds/F) and clearance in the peritoneal cavity (CLp) for mitomycin C
      (78 L m-2 and 1.8 L h-1 m-2) were about twice the values for 5-fluorouracil (149
      L m-2 and 0.8 L h-1 m-2).

PMID- 7815286
TI  - Separation and quantification of murein and precursors from Enterobacter cloacae
      after treatment with trimethoprim and sulphadiazine.
AB  - The intracellular concentrations of the soluble murein precursors UDP-Mur-NAc
      pentapeptide in the cytoplasm, the membrane-bound lipid precursor disaccharide
      pentapeptide and the muropeptides of Enterobacter cloacae cultures treated with
      trimethoprim (12.5 micrograms mL-1) and sulphadiazine (250 micrograms mL-1) were
      determined by using capillary zone electrophoresis analysis. In the presence of
      trimethoprim, UDP-Mur-NAc-pentapeptide as well as disaccharide pentapeptide
      accumulated. In the case of sulphadiazine-treated cells, the concentration of UDP
      Mur-NAc-pentapeptide roughly paralleled the control cells but sulphadiazine
      caused a slow incremental accumulation of disaccharide pentapeptide. The
      muropeptide composition of the murein indicated that the differences between the
      peptidoglycans produced by the control cells and the cells grown in the presence
      of either trimethoprim or sulphadiazine alone or in combination were quite
      marked. The results suggest that the enhanced activity of trimethoprim plus
      sulphadiazine against E. cloacae is caused by an additional effect on the
      inhibition of the bacterial peptidoglycan biosynthesis and that this additional
      effect is a fundamental part of the antibacterial action of the antimetabolites.
      This effect leads to changes of cell morphology and resultant changes in
      bacterial cell permeability.

PMID- 7815287
TI  - Health care environmentalism.

PMID- 7815288
TI  - Supraventricular tachycardia in children: a challenge for pediatric nurses.
AB  - Supraventricular tachycardia (SVT) in the pediatric population remains the most
      common dysrhythmia for this age group. Care of these children and their families
      can provide a challenge for the pediatric nurse as well as many rewards. This
      report will explore the mechanisms of SVT in children, their clinical
      presentation, currently available treatment options, and the nursing implications
      of caring for these children and their families.

PMID- 7815289
TI  - Factors influencing the coping of hospitalized school-age children.
AB  - Factors influencing the coping process in hospitalized children were examined by
      studying the effect of health status (acutely or chronically ill), gender, and
      trait anxiety on the coping behaviors used in response to intrusive hospital
      events and the perceived effectiveness of the overall coping process used during
      hospitalization. The sample consisted of 82 children, age 8 through 11 years,
      hospitalized in an acute care pediatric unit in one of six California hospitals.
      Data were obtained on the second or third day of admission, through interview,
      word graphic rating scale, and State-Trait Anxiety Inventory for Children
      (STAIC). Significant results indicated that acutely ill children are more likely
      to perceive their coping as effective than are chronically ill children, and
      children with low trait anxiety are more likely to perceive their coping
      behaviors as effective than do those with high anxiety.

PMID- 7815290
TI  - Pain management and potentially life-shortening analgesia in the terminally ill
      child: the ethical implications for pediatric nurses.
AB  - Optimal pain control in the dying child often requires aggressive opioid therapy
      that exceeds recommended parameters and may hasten death caused by respiratory
      depression. For pediatric nurses caring for the dying child, the administration
      of potentially life-shortening analgesia gives rise to a number of ethical
      issues. Pediatric nurses often express concern that aggressive pain control is a
      form of euthanasia or fear the child will develop a drug dependence. Lack of
      clarity about the ethical obligations and professional responsibilities of nurses
      who administer potentially life-shortening analgesia may also contribute to the
      dilemmas surrounding such situations. If left unresolved, these issues can
      interfere with the nurse's ability to implement an appropriate pain regimen. To
      provide adequate pain control, pediatric nurses who care for dying children must
      accomplish the following: critically examine ethical issues and underlying
      principles; understand the phenomena of addiction, tolerance, and physical
      dependence; and identify the boundaries of acceptable nursing practice when
      administering potentially life-shortening analgesia to terminally ill children.

PMID- 7815291
TI  - Munchausen syndrome by proxy: an exploratory study of pediatric nurses' knowledge
      and involvement.
AB  - The awareness and involvement of pediatric nurses in the type of child abuse
      known as Munchausen syndrome by proxy (MSBP) was explored in this study. A
      questionnaire assessing knowledge about and extent of involvement in the
      identification of MSBP cases and demographic information was completed by 320
      registered nurses (RNS) employed at a children's hospital. Fewer than half of the
      subjects (47%) responded that they had heard of MSBP. Those who had heard of MSBP
      demonstrated only a moderate level of knowledge of the signs and signals of the
      syndrome. Thirty-four percent of those nurses who had heard of MSBP had been
      involved in the detection of cases. Findings suggest that it might be important
      for pediatric hospitals to include information about MSBP in their own required
      classes or in-house seminars.

PMID- 7815292
TI  - A reproductive option for women with Turner's syndrome.
AB  - In the past, management of congenital absence of ovaries in women with Turner's
      syndrome (TS) was limited to replacement of ovarian hormones to initiate pubertal
      development. Until recently, adoption or stepparenting were the only parenting
      options. However, with new developments in assisted reproduction, women with TS
      may be able to successfully complete pregnancy and childbearing. There are
      specific nursing considerations for children and adolescents to follow:
      anticipatory guidance regarding sexual development; encouraging discussions of
      the range of options that are available for women with TS regarding reproduction;
      and assisting these children and adolescents in understanding the benefits and
      limitations associated with one reproductive option, in vitro fertilization.

PMID- 7815294
TI  - Community nursing centers: an approach to caring for the underserved.

PMID- 7815293
TI  - Strategy for promoting greater responsiveness in adolescent parent/infant
      relationships: report of a pilot study.
AB  - A small pilot study tested an interaction coaching procedure designed to increase
      the level of responsiveness in adolescent parent/infant interaction behavior with
      12 teenage parents and their infants. There was a significant increase in the
      level of responsiveness and parental self-esteem scores after the intervention
      compared with those before the intervention. Although the sample size was small,
      the results are encouraging and suggest further development of the intervention,
      Interaction Coaching for Adolescent Parents and their Infants (ICAP).

PMID- 7815295
TI  - Equipment safety for infants and children: beyond clinical practice.

PMID- 7815296
TI  - Using a health education approach to develop and evaluate a program for parents
      of children with human immunodeficiency virus infection.

PMID- 7815297
TI  - Research in pediatric nursing at a Colombian University.

PMID- 7815298
TI  - Identity negotiation in roommate relationships: the self as architect and
      consequence of social reality.
AB  - The authors report two longitudinal studies of new college roommates (Ns = 69 and
      95 pairs). In both studies, targets' initial self-views predicted changes in
      perceivers' appraisals of them, and perceivers' initial appraisals predicted
      changes in targets' self-views, although few dyads displayed both effects. The
      perceiver-driven and target-driven effects occurred when appraisals and self
      views were negative as well as positive. Implications for self-verification
      theory and symbolic interactionism are discussed, and a less restrictive model of
      how appraisals influence self-views is proposed.

PMID- 7815299
TI  - Enhanced co-orientation in the perception of friends: a social relations
      analysis.
AB  - Newcomb's (1953) idea of co-orientation (interdependence between two persons'
      attitudes or perceptions) is used as a framework within which interpersonal
      perception between friends and acquaintances is examined. The principal question
      is whether co-orientation effects are stronger for friendship dyads than for
      acquaintance dyads. More specifically, the study examines the degree to which
      consensus, assimilation, self-other agreement, and assumed similarity differ. The
      social relations model is used to analyze a data set that included 16 living
      groups with 119 friend dyads and 1.668 acquaintance dyads. Results indicate that
      co-orientation effects are more pronounced in friendship dyads. The increment in
      co-orientation effects is largely due to similarities in the unique or
      idiosyncratic perceptions that people have of friendship pairs as well as the
      unique agreement about others that friends have with one another.

PMID- 7815300
TI  - Divergent worlds: the daily emotional experience of mothers and fathers in the
      domestic and public spheres.
AB  - This study compared the emotional states experienced by mothers and fathers
      during daily activities in the domestic and public spheres. Participants carried
      pagers for 1 week and reported their states when signaled at random times.
      Patterns for mothers and fathers differed markedly. Mothers reported more
      positive states in activities away from home, including during work at a job.
      These states were related to the perceived friendliness of co-workers. Fathers
      reported more positive states in the home sphere, partly because they spent more
      of this time n personal and recreational activities and partly because they
      experienced more choice, even during family work.

PMID- 7815301
TI  - Individual differences in need for cognitive closure.
AB  - This article introduces an individual-difference measure of the need for
      cognitive closure. As a dispositional construct, the need for cognitive closure
      is presently treated as a latent variable manifested through several different
      aspects, namely, desire for predictability, preference for order and structure,
      discomfort with ambiguity, decisiveness, and close-mindedness. This article
      presents psychometric work on the measure as well as several validation studies
      including (a) a "known-groups" discrimination between populations assumed to
      differ in their need for closure, (b) discriminant and convergent validation with
      respect to related personality measures, and (c) replication of effects obtained
      with situational inductions of the need for closure. The present findings suggest
      that the Need for Closure Scale is a reliable and valid instrument of
      considerable potential utility in future "motivated social cognition" research.

PMID- 7815302
TI  - Distinguishing optimism from neuroticism (and trait anxiety, self-mastery, and
      self-esteem): a reevaluation of the Life Orientation Test.
AB  - Research on dispositional optimism as assessed by the Life Orientation Test
      (Scheier & Carver, 1985) has been challenged on the grounds that effects
      attributed to optimism are indistinguishable from those of unmeasured third
      variables, most notably, neuroticism. Data from 4,309 subjects show that
      associations between optimism and both depression and aspects of coping remain
      significant even when the effects of neuroticism, as well as the effects of trait
      anxiety, self-mastery, and self-esteem, are statistically controlled. Thus, the
      Life Orientation Test does appear to possess adequate predictive and discriminant
      validity. Examination of the scale on somewhat different grounds, however, does
      suggest that future applications can benefit from its revision. Thus, we also
      describe a minor modification to the Life Orientation Test, along with data
      bearing on the revised scale's psychometric properties.

PMID- 7815303
TI  - Depression and everyday social interaction.
AB  - The present study examined the relationships between depressive symptoms and
      everyday social interaction in a nonclinical population. Depressive symptoms were
      measured using the Center for Epidemiological Studies Depression Scale, and
      social interaction was measured using a variant of the Rochester Interaction
      Record. People who were classified as at risk for depression had less rewarding
      interactions than people who were not at risk. Depressive symptoms and
      interaction quantity and quality were negatively correlated for participants
      above the cutpoint, whereas they were uncorrelated for those below the at-risk
      cutpoint. The results also suggested that, compared with nondepressed people,
      depressed people derive more rewards from interactions with their closest
      opposite-sex friends, relative to the rewards they derive from interactions with
      other opposite-sex friends.

PMID- 7815304
TI  - Mutations affecting gluconate catabolism in Escherichia coli. Genetic mapping of
      loci for the low affinity transport and the thermoresistant gluconokinase.
AB  - The isolation and properties of strains of Escherichia coli carrying mutations
      affecting either the low affinity transport for gluconate (gene gntU) or the
      thermoresistant gluconokinase (gene gntK) are described. A lesion of each type
      was genetically characterized by transduction experiments. Both mutations mapped
      in the asd region, and the order was malA-glpD-asd-gntU-gntK, with the last two
      markers at about min 75.78 and 75.86 on the map, respectively. Mutations altering
      specifically gntU have not been previously reported.

PMID- 7815306
TI  - Osmotolerant yeasts isolated from Tokaj wines.
AB  - Yeasts growing in "Tokaj Aszu" wine and in "Aszu essence" were isolated and
      characterised. They proved to be physiological races of Saccharomyces cerevisiae
      and showed high osmotolerance, which was an inherited feature rather than the
      result of adaptation. No correlations were found between the osmotolerance and
      the ethanol tolerance or the cell size and morphology. Yeasts in "Aszu essence"
      are usually undesirable contaminants that impair the quality of the essence. The
      isolate characterized in this work exhibited physiological parameters very
      similar to those of the "Tokaj Aszu" strain, which make it a potent competitor of
      other yeasts in Aszu fermentation. However, the high termo sensitivity of its
      cells offers a possibility to eliminate them selectively.

PMID- 7815305
TI  - Catabolite repression of cellulase biosynthesis in Streptomyces albaduncus.
AB  - The cellulase complex of S. albaduncus was found to undergo catabolite repression
      in the presence of glycerol accompanied by a decrease in the pH of the medium.
      The results of the experiments conducted at two different initial pH of the
      medium suggested that pH effect as well as proteases were involved in the
      inactivation of glucanases (exoglucanase and endoglucanase) whereas beta
      glucosidase inactivation was solely due to 'pH effect'. It was also apparent that
      pH change followed by the addition of glycerol caused alterations in protease
      activities as well as pattern of their production.

PMID- 7815307
TI  - Effect of inhibitors of cell envelope synthesis on beta-sitosterol side chain
      degradation by Mycobacterium sp. NRRL MB 3683.
AB  - The role of the lipid bilayer and the peptidoglycan of the mycobacterial cell
      wall in the permeation of beta-sitosterol into the cell and its transformation to
      androst-1-ene-3,17-dione (AD) and androsta-1,4-diene-3,17-dione (ADD) was
      studied. Specific inhibitors were used at concentrations affecting the
      biosynthesis of the assumed target structures, but causing only partial cell
      growth inhibition or exerting no effect on growth. m-Fluorophenylalanine and DL
      norleucine which are known to disorganize the biosynthesis of amphipatic
      components of the outer layer of the lipid bilayer, used at concentrations 250
      micrograms/ml and 400 micrograms/ml, respectively, increased the formation rate
      of AD+ADD from 0.3 (control) to 0.7 and 0.8 mg products/g dry weight/h. The
      disorganization of the underlying mycolyl-arabinogalactan structure by the action
      of the ethambutol at the concentration 40 micrograms/ml, at which the cell growth
      was apparently not affected, caused the decrease of the product formation from
      135 mg/l to 70 mg/l. In the presence of isoniazid (350 micrograms/ml) only trace
      amounts of AD accumulated during 48 hours of transformation indicating much lower
      activity than that of the intact cells. The most effective among the tested
      inhibitors of peptidoglycan synthesis were glycine (15 mg/ml) and vancomycin (150
      micrograms/ml) which enhanced the transformation activity of the treated cells
      nearly three times. Increased transformation rate was also obtained by the action
      of colistin at concentrations ranging from 10 micrograms/ml to 15 micrograms/ml.

PMID- 7815308
TI  - The Bateman function revisited: a critical reevaluation of the quantitative
      expressions to characterize concentrations in the one compartment body model as a
      function of time with first-order invasion and first-order elimination.
AB  - The Bateman function, A"(e-k(e)t--e-k(a)t), quantifies the time course of a first
      order invasion (rate constant ka) to, and a first-order elimination (rate
      constant ke) from, a one-compartment body model where A" = (gamma Dose)ka/(ka
      ke)V. The rate constants (when ka > 3ke) are frequently determined by the "method
      of residuals" or "feathering." The rate constant ka is actually the sum of rate
      constants for the removal of drug from the invading compartment. "Flip-flop," the
      interchange of the values of the evaluated rate constants, occurs when ke > 3ka.
      Whether -ka or -ke is estimable from the terminal ln C-t slope can be determined
      from which apparent volume of distribution, V, derived from the Bateman function
      is the most reasonable. The Bateman function and "feathering" fail when the rate
      constants are equal. The time course is then expressed by C = gamma Dtk e-kt. The
      determination of such equal k values can be obtained by the nonlinear fitting of
      such C-t data with random error to the Bateman function. Also, rate constant
      equality can be concluded when 1/tmax and the kmin (value of ke at the minimum
      value of ek(e)tmax/ke plotted against variable ke values) are synonymous or when
      kmintmax approximates unity. Simpler methods exist to evaluate C-t data. When a
      drug has 100% bioavailability, regression of Dose/V/C on AUC/C in the
      nonabsorption phase gives ke no matter what is the ratio of m = ka/ke. Since
      k(e)tmax = ln m/(m-1), m can be determined from the given table relating m and
      k(e)tmax. When gamma is unknown, ke can be estimated from the abscissas of
      intersections of plots of Cmax ek(e)tmax and keAUC, both plotted vs. arbitrary
      values of ke, and gamma D/V values are estimable from the ordinate of the
      intersection. Also, when gamma is unknown, ke can be estimated from the abscissas
      of intersections (or of closest approaches) of ek(e)tmax/ke and AUC/Cmax, both
      plotted vs. arbitrary values of ke. The C-t plot of the Modified Bateman
      function, C = Be-lambda 2t-A e-lambda 1t, does not commence at the origin (i.e.,
      when tc = 0 = 0 and when a lag time does not exist).(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7815309
TI  - Application of optimal sampling theory to the determination of metacycline
      pharmacokinetic parameters: effect of model misspecification.
AB  - Use of optimal sampling theory (OST) in pharmacokinetic studies allows the number
      of sampling times to be greatly reduced without loss in parameter estimation
      precision. OST has been applied to the determination of the bioavailability
      parameters (area under the curve (AUC), maximal concentration (Cmax), time to
      reach maximal concentration (Tmax), elimination half-life (T1/2), of metacycline
      in 16 healthy volunteers. Five different models were used to fit the data and to
      define the optimal sampling times: one-compartment first-order, two-compartment
      first-order, two-compartment zero-order, two-compartment with Michaelis-Menten
      absorption kinetics, and a stochastic model. The adequacy of these models was
      first evaluated in a 6-subject pilot study. Only the stochastic model with zero
      order absorption kinetics was adequate. Then, bioavailability parameters were
      estimated in a group of 16 subjects by means of noncompartmental analysis (with
      19 samples per subject) using each optimal sampling schedule based procedure
      (with 6 to 9 samples depending on the model). Bias (PE) and precision (RMSE) of
      each bioavailability parameter estimation were calculated by reference to
      noncompartmental analysis, and were satisfactory for the 3 adequate models. The
      most relevant criteria for discrimination of the best model were the coefficient
      of determination, the standard deviation, and the mean residual error vs. time
      plot. Additional criteria were the number of required sampling times and the
      coefficient of variation of the estimates. In this context, the stochastic model
      was superior and yielded very good estimates of the bioavailability parameters
      with only 8 samples per subject.

PMID- 7815311
TI  - A technique for calculating the mean time for equilibration of drug distribution
      using minimal structural assumptions.
AB  - Disposition decomposition analysis is used as a framework to derive a parameter
      for the description of drug distribution kinetics. This parameter, denoted td, is
      a measure of the mean time for equilibration of distribution in the absence of
      metabolic drug elimination. The derivation requires only the assumption that
      distribution is linear, and is generally valid as long as any nonlinearity is due
      to central nonlinear elimination. The mean time for equilibration of
      distribution, td, is evaluated in terms of the moments of the distribution
      function, h(t), derived by disposition decomposition analysis. Estimates of td
      for several drugs are presented.

PMID- 7815310
TI  - Pharmacokinetics of rec-hirudin in healthy volunteers after intravenous
      administration.
AB  - The pharmacokinetics of recombinant hirudin (rec-hirudin, Ciba-Geigy, CGP 39,393)
      in healthy volunteers after iv administration was investigated on the basis of
      the data from five different studies. A total of 77 plasma profiles following a
      single iv bolus dose of either 0.1, 0.3, 0.5, or 1 mg/kg of rec-hirudin was used
      for the evaluation. Plasma concentrations and especially AUC were proportional to
      the dose. Kinetics of rec-hirudin after a bolus iv injection were best described
      by a three-compartment open model. Mean apparent terminal half-life was 2.8 hr
      and the total clearance 0.138 L/hr per kg.

PMID- 7815312
TI  - Interaction between structural, statistical, and covariate models in population
      pharmacokinetic analysis.
AB  - The influence of the choice of pharmacokinetic model on subsequent determination
      of covariate relationships in population pharmacokinetic analysis was studied
      using both simulated and real data sets. Simulations and data analysis were both
      performed with the program NONMEM. Data were simulated using a two-compartment
      model, but at late sample times, so that preferential selection of the two
      compartment model should have been impossible. A simple categorical covariate
      acting on clearance was included. Initially, on the basis of a difference in the
      objective function values, the two-compartment model was selected over the one
      compartment model. Only when the complexity of the one-compartment model was
      increased in terms of the covariate and statistical models was the difference in
      objective function values of the two structural models negligible. For two real
      data sets, with which the two-compartment model was not selected preferentially,
      more complex covariate relationships were supported with the one-compartment
      model than with the two-compartment model. Thus, the choice of structural model
      can be affected as much by the covariate model as can the choice of covariate
      model be affected by the structural model; the two choices are interestingly
      intertwined. A suggestion on how to proceed when building population
      pharmacokinetic models is given.

PMID- 7815313
TI  - Transitional suck patterns in premature infants.

PMID- 7815314
TI  - Critical care obstetrics: experts' round table discussion.
AB  - A panel of leading experts in critical care obstetric (CCOB) nursing met to
      discuss the specialty and its future, the impact of changes in the health care
      system, educational opportunities to learn and update CCOB nursing, formation and
      use of standards for the specialty, patient placement (dedicated obstetric
      intensive care units [OB ICU], labor and delivery intensive care units [L & D
      ICU], regular intensive care units [ICU]), patient populations, and interactions
      and working relationships with the physicians who care for CCOB patients
      (perinatologists, obstetricians, internists, obstetric medicine specialists,
      anesthesiologists, other subspecialists). The topics for discussion were chosen
      by Carol J. Harvey, RNC, MS, who acted as moderator and Mary Ellen Burke, RN, MS,
      coordinated the publication of the discussion.

PMID- 7815315
TI  - Strategies for establishing a critical care obstetric service.
AB  - Critical care obstetrics is gaining increased recognition as a subspecialty of
      perinatal medicine. As the specialty continues to expand, many institutions may
      consider establishing a critical care obstetric service. However, implementing
      such a service is not feasible for every institution because of space
      limitations, budgetary constraints, lack of necessary resources, and/or a limited
      number of critically ill obstetric patients. This article explores strategies for
      examining the feasibility of establishing a critical care obstetric service,
      suggests methods of implementation, and offers an alternative when establishing a
      critical care obstetric service is not feasible.

PMID- 7815316
TI  - A curriculum to develop critical care obstetric nursing staff.
AB  - Orientation of perinatal nursing staff to critical care obstetrics is vital to
      provide comprehensive, high-quality care for high-risk populations. One approach
      is to offer an intensive critical care obstetrics program in house that offers
      theoretical and practical experience and makes use of resources and talents
      within the institution.

PMID- 7815317
TI  - Critical care obstetrics: the role of advanced practice nursing.
AB  - The role of the advanced practice nurse in the specialty of critical care
      obstetric nursing is emerging to meet the dynamic needs of health care under
      reform. Advanced practice components, including case management, research
      utilization, collaborative consultation, and advanced educational preparation,
      give light to a new model of caregiver. This article details the educational
      preparation and specific roles of the advanced practice nurse in the specialty of
      critical care obstetrics.

PMID- 7815318
TI  - Neonatal case management: a challenge for advanced practice nurses.
AB  - With a presidential commitment to health care reform, advanced practice nurses
      (APNs) are challenged to rethink critical care for the growing number of
      premature infants born each year. Threats of shortened lengths of stay force APNs
      to case manage the long-term needs of compromised neonates in their homes and
      communities. Recent studies have shown that earlier discharge from neonatal
      intensive care units with proper home follow-up is not only cost saving, but is
      also safe and beneficial to the infant and family. Further documentation is
      required to ensure that quality outcomes are not compromised in health care
      reform.

PMID- 7815319
TI  - Parents' perceptions of nursing support following neonatal loss.
AB  - This retrospective descriptive study evaluated the perceptions of a convenience
      sample of 23 grieving parents who were members of Resolve Through Sharing in the
      southcentral United States. Data from two investigator-designed questionnaires
      were analyzed with descriptive statistics. Categories utilized were:
      acknowledgment of baby, education/information/written material, and general
      emotional support (communication/interventions). Interventions dealing with
      acknowledgment of the infant were reported as most beneficial. Others were rated
      as beneficial to varying degrees. It is imperative that nurses provide parents
      with research-based support to assist them in beginning a healthy grieving
      process.

PMID- 7815320
TI  - Caring in a neonatal intensive care unit: perspectives of providers and
      consumers.
AB  - Neonatal intensive care units have continually grown in number and complexity in
      their short history. The care given to infants and families in these units is
      done, in large part, by nursing. This article discusses the development of a
      scale that will explore the perceptions of this care by both consumers and
      providers. The perceptions of each group will be compared to determine if care
      that is thought and intended to be caring for providers is indeed perceived as
      such by consumers. This is of significant importance to the developing body of
      knowledge related to caring in nursing, and it will also promote care that is
      family centered.

PMID- 7815321
TI  - Bidirectional effects of endogenous opioid peptides on endothelin release rates
      in porcine aortic endothelial cell culture: mediation by delta opioid receptor
      and opioid receptor antagonist-insensitive mechanisms.
AB  - The effects of opioid peptides on immunoreactive endothelin (ir ET) release from
      cultured porcine aortic endothelial cells over a 1-hr period (4-5 or 23-24 hr)
      were determined by radioimmunoassay and high-performance liquid chromatography
      after treatment for either 4 or 23 hr. Endogenous opioids, the synthetic delta
      opioid [D-Pen2,5]enkephalin and, for comparison, atrial and brain natriuretic
      peptides were added to the culture medium in concentrations ranging from 10(-12)
      to 10(-7) M. Thrombin (0.1-10 U/ml) served as a stimulatory reference. 1) Brain
      natriuretic peptide displayed only insignificant effects on ir ET release at 5
      hr, but strongly inhibited ir ET release at 24 hr. 2) Opioids modulated release
      rates at 5 hr but did not display significant effects at 24 hr: metorphamide with
      predominant mu/kappa and weak delta opioid receptor activity stimulated release
      in a dose-dependent manner, whereas [Met5]enkephalin-Arg6-Phe7 with mu/delta
      activity and the delta agonists [Leu5]enkephalin, sulfated [Leu5]enkephalin and
      [D-Pen2,5]enkephalin decreased release rates; [Leu5]enkephalin was the most
      potent of the latter drugs. 3) Coincubation with either the nonselective opioid
      receptor antagonist naloxone (10(-5) M) or the delta receptor-selective
      antagonist ICI-174,864 (N,N-bisallyl-Tyr-D-Ala-Aib-Aib-Phe-Leu-OH) (10(-5) M)
      abolished all opioid-induced inhibitory effects, but rather potentiated or
      unmasked stimulatory effects of opioid peptides on ir ET release rates at 5 hr
      and also at 24 hr in the case of the delta agonists.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7815323
TI  - Effects on ethanol withdrawal hyperexcitability of chronic treatment with a
      competitive N-methyl-D-aspartate receptor antagonist.
AB  - The effects of the competitive N-methyl-D-aspartate receptor antagonist DL-(E)-2
      amino-4-methyl-5-phosphonopentanoate carboxy-ethylester (CGP39551) on the
      hyperexcitability produced by withdrawal from chronic ethanol treatment were
      studied in mice, to which CGP39551 was given chronically with the ethanol. When
      an interval of 72 or 96 hr was left between the last of the repeated CGP39551
      injections and withdrawal from ethanol, the severity of the ethanol withdrawal
      syndrome was increased. When shorter time intervals were left between the end of
      the CGP39551 treatment and the ethanol withdrawal, the chronic CGP39551 treatment
      protected against the withdrawal hyperexcitability. When a single low dose of
      CGP39551 was given immediately after ethanol withdrawal, the compound protected
      against the withdrawal hyperexcitability. It is therefore suggested that the
      protective effects of concurrent chronic treatment with CGP39551, seen when the
      shorter intervals were allowed, were caused by residual compound. The increased
      severity of withdrawal, when sufficient time was left for washout of CGP39551,
      suggests that chronic administration of CGP39551 increased the adaptive changes
      that cause or contribute to ethanol withdrawal hyperexcitability. The results
      differ from the previously reported effects of N-methyl-D-aspartate antagonists
      on ethanol tolerance, because this was reduced by concurrent chronic treatment.
      They are also in contrast with the effects of chronic dihydropyridine calcium
      channel antagonists, which decreased both the development of tolerance and the
      ethanol withdrawal syndrome, when given chronically, concurrently with the
      ethanol. Cessation of prolonged ethanol intake results in a period of neuronal
      hyperexcitability, described as the withdrawal or abstinence syndrome.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7815322
TI  - Drug discrimination analysis of midazolam under a three-lever procedure: I. Dose
      dependent differences in generalization and antagonism.
AB  - Twelve rats were trained to discriminate two doses of midazolam, 0.32 and 3.2
      mg/kg, from no drug under a three-lever, multiple-trials procedure (15-min time
      out, 5-min fixed-ratio-10 schedule of food reinforcement). In tests, midazolam
      (0.0032-10 mg/kg), administered cumulatively within a session or acutely across
      sessions, produced dose-dependent increases in responding on the low-dose lever
      after 0.1 to 1.0 mg/kg and on the high-dose lever at higher doses in all rats.
      Flumazenil dose-dependently antagonized the discriminative stimulus effect of 3.2
      mg/kg of midazolam in all rats but antagonism of the lower midazolam training
      dose was not obtained in all rats. Pentobarbital dose-dependently produced
      responding on the levers associated with the no-drug and 0.32-mg/kg midazolam
      conditions but not on the lever associated with 3.2 mg/kg of midazolam. These
      results differed from those that would have been predicted from studies in
      midazolam-trained rats in two-lever procedures. The muscle relaxant methocarbamol
      and nonsedative/anxiolytic drugs (morphine, caffeine and d-amphetamine) did not
      produce responding on the lever associated with either the low or high midazolam
      training dose. However, cocaine produced partial responding on the lever
      associated with the low midazolam dose. Thus, the discriminative stimulus effects
      of 3.2 mg/kg of midazolam were benzodiazepine-like and not a function of general
      sedative or muscle-relaxant effects. The 0.32-mg/kg midazolam training dose, in
      this context, appeared less specific than 3.2 mg/kg of midazolam. Taken together,
      the results suggest that not all differences among the training stimuli in this
      three-lever context reflect simple differences in dose.

PMID- 7815324
TI  - Quantitation of the renal clearance of interleukin-2 using nephrectomized and
      ureter-ligated rats.
AB  - The objective of this work was to determine the role of the kidneys in the
      systemic clearance rate (CL) of interleukin-2 (IL-2). Rats received IL-2 by i.v.
      bolus and the pharmacokinetic data were found to be well described by a two
      compartment, first-order elimination model. With administration of 0.2, 0.5 or
      1.0 mg/kg of IL-2 (n = 3 per treatment), the median alpha and beta half-lives
      (T1/2 alpha, 2.3 min; T1/2 beta, 13.2 min, respectively), initial volume of
      distribution (V1, 93 ml/kg), volume of distribution at steady state (Vss, 198
      ml/kg) and CL (16.8 ml min-1 kg-1) did not vary with the dose (P = .05). This
      demonstration of first-order kinetics suggested that renal CL remains constant
      over a range of doses. The pharmacokinetic properties of 1.0 mg/kg of IL-2 were
      examined after either single or double nephrectomy (n = 3 and 4, respectively),
      sham operation (n = 4) or no renal operation (n = 4; the "controls"). No
      difference in median T1/2 alpha, T1/2 beta, V1, Vss or CL was detected between
      control and sham-operated rats nor between single nephrectomy and sham operation.
      Compared with sham operation, double nephrectomy showed no significant change in
      V1 or Vss but the T1/2 alpha and T1/2 beta approximately doubled and CL was
      reduced by 75%. In a separate experiment, ureter-ligated rats were compared with
      sham-operated rats. With ureter ligation, T1/2 alpha, T1/2 beta, V1 and Vss were
      unchanged but CL was reduced by 36%.

PMID- 7815325
TI  - Cloning and pharmacological characterization of human alpha-1 adrenergic
      receptors: sequence corrections and direct comparison with other species
      homologues.
AB  - We have cloned cDNAs encoding three human alpha-1 adrenergic receptor (AR)
      subtypes and characterized pharmacological properties of the expressed receptor
      protein. A number of significant sequence corrections have been identified and
      compared with previously published data, at both nucleotide and amino acid
      levels; the most major differences occur for the human alpha-1a/dAR.
      Pharmacological characterization was performed simultaneously using six cloned
      alpha-1AR subtypes (human and rat alpha-1a/d, human and hamster alpha-1b, human
      and bovine alpha-1c) stably expressed in rat-1 fibroblasts at approximately equal
      receptor concentrations (1-2 pmol/mg of total protein). In general, human alpha
      1AR subtypes have similar pharmacology compared to their rat, hamster and bovine
      homologs, although a few minor species differences important for alpha-1AR
      classification are noted. In addition, much lower inactivation (approximately
      20%) by the alkylating agent chloroethylclonidine is noted in this study compared
      to previous reports for both human and bovine alpha-1cAR membrane preparations.
      All six alpha-1AR subtypes couple to phosphoinositide hydrolysis in a pertussis
      toxin-insensitive manner, including the cloned human alpha-1a/dAR which had not
      been expressed previously. In spite of significant sequence differences between
      human alpha-1ARs and their other species counterparts, previously established
      ligand selectivity remains fairly comparable. In summary, these data represent
      the first side-by-side comparison of pharmacological properties between species
      homologs of alpha-1AR subtypes and should facilitate the development of alpha-1AR
      subtype selective drugs for clinical use.

PMID- 7815326
TI  - 5-Hydroxytryptamine2B receptor signaling in rat stomach fundus: role of voltage
      dependent calcium channels, intracellular calcium release and protein kinase C.
AB  - The rat stomach fundus is enriched with the 5-hydroxytryptamine (5-HT)2B
      receptor, the newest subtype of the 5-HT2 receptor family to be cloned. Although
      the 5-HT2A and 5-HT2C receptor subtypes couple to phosphatidylinositol
      hydrolysis, such a coupling has not been established for the 5-HT2B receptor in
      tissues. Thus, the purpose of this study was to characterize further the signal
      transduction mechanism of the 5-HT2B receptor in rat stomach fundus. Nitrendipine
      (1 microM) inhibited the maximal contraction to 5-HT (1 microM) by approximately
      50%. Removal of extracellular calcium did not inhibit 5-HT contraction to a
      greater extent than that produced by nitrendipine, indicating that calcium influx
      through voltage-dependent calcium channels was predominantly responsible for the
      dependence of the 5-HT contraction on extracellular calcium. Depletion of both
      extracellular calcium and intracellular calcium stores abolished 5-HT
      contraction. Ryanodine (30 microM), a compound which inhibits calcium release
      from intracellular stores, significantly inhibited the maximal contraction to
      carbamylcholine (3 microM). In contrast, ryanodine (30 microM) did not inhibit
      the maximal contraction to 5-HT (1 microM) in the absence of nitrendipine.
      However, ryanodine (30 microM) did significantly inhibit the nitrendipine
      insensitive 5-HT contraction, suggesting that this component of the contraction
      was due in part to calcium release from a ryanodine-sensitive store.
      Bisindolylmaleimide (5 microM), a specific inhibitor of protein kinase C (PKC),
      inhibited 5-HT contraction in either the absence or presence of nitrendipine,
      suggesting that activation of PKC is also involved.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7815327
TI  - Up-regulation of brain PGE2 and PGF2 alpha receptors and receptor-coupled second
      messengers by cyclooxygenase inhibition in newborn pigs.
AB  - We recently reported that brain synaptosomes of newborn pigs contained fewer PGE2
      (EP) and PGF2 alpha (FP) receptors than adult tissues. In the present study we
      investigated whether this was the result of down-regulation of these receptors by
      high levels of PGE2 and PGF2 alpha in the brain of newborn animals. Newborn pigs
      (1-3 days old) were treated with ibuprofen (40 mg/kg) or indomethacin (5 mg/kg)
      i.v. every 4 hr for 24 hr to reduce prostaglandins to adult levels. At the end of
      the treatment, EP and FP receptor density and receptor-linked second messenger
      formation in brain synaptosomes were measured. It was found that ibuprofen and
      indomethacin treatment increased EP and FP receptor densities in brain
      synaptosomes of newborn animals to levels found in the adult; this up-regulation
      of EP receptors was prevented by EP receptor agonist, 16,16-dimethyl-PGE2, and
      the up-regulation of FP receptors was prevented by the FP agonist, fenprostalene.
      PGE2, butaprost (an agonist for EP2 receptor subtype mediating cAMP stimulation)
      and 11-deoxy-PGE1 (an agonist for EP2 and EP3 receptors) caused a comparable
      increase of cAMP in brain synaptosomes of ibuprofen-treated and adult animals,
      which was significantly greater than in those of vehicle-treated animals. Also,
      PGF2 alpha and its analog, fenprostalene, caused a much greater increase in IP3
      production in brain synaptosomes of ibuprofen-treated than in vehicle-treated
      pigs. These findings suggest that the relatively low EP and FP receptor densities
      in newborn pigs are caused by the high levels of prostaglandins and that these
      receptors can be up-regulated by inhibiting prostaglandin synthesis.

PMID- 7815329
TI  - The effect of acyl CoA: cholesterol acyltransferase inhibition on the uptake,
      esterification and secretion of cholesterol by the hamster small intestine.
AB  - Acyl CoA: cholesterol acyltransferase (ACAT) inhibitors are known to inhibit
      cholesterol absorption and are under investigation to reduce
      hypercholesterolemia. These studies examine the effect of an ACAT inhibitor 2,2
      dimethyl-N-(2,4,6-trimethoxyphenyl)-dodecanamide (PD128042) on the uptake,
      metabolism and secretion of cholesterol by the hamster intestinal wall in a short
      term model. Preliminary studies in this model indicated that the uptake of 14C
      cholesterol and its subsequent esterification 2 hr postoral dosing occurs
      primarily in the duodenal and jejunal segments of the small intestine and most of
      the radiolabeled cholesterol and cholesteryl ester in the plasma was associated
      with chylomicrons. In both single- and multiple-dose studies, PD128042 (50 mg kg
      1 day-1) did not inhibit intestinal uptake of [14C]-cholesterol but [14C]
      cholesteryl ester formation was inhibited. The free [14C]-cholesterol appearing
      in plasma was not affected despite a large reduction in [14C]-cholesteryl ester.
      In contrast, cholestyramine (1 g kg-1 day-1) inhibited the uptake of the
      radiolabeled free cholesterol and the appearance of cholesteryl ester in the
      intestine and plasma. The effects of PD128042 on cholesterol and cholesteryl
      ester mass associated with scraped intestinal mucosa were consistent with the
      effects observed with the use of the radiolabeled cholesterol. In addition,
      PD128042 did not affect the uptake of appearance of radiolabeled triglyceride in
      the intestinal wall after oral gavage of 3H-trioleoylglycerol. Taken together,
      the data suggest that ACAT inhibition reduces cholesterol absorption by limiting
      cholesteryl ester incorporation into chylomicrons and has no effect on the
      intestinal processing of free cholesterol to be secreted into plasma.

PMID- 7815328
TI  - The effect of cigarette smoking on adrenal cortical hormones.
AB  - We assessed the association between cigarette smoking and basal levels of adrenal
      cortical hormones in 11 postmenopausal smokers and 11 postmenopausal nonsmokers
      and measured the acute adrenal effects of cigarettes in the smokers. After an
      overnight food, alcohol and tobacco fast, participants smoked or sham-smoked
      every hr for 8 hr and provided serum samples for hormone assay before and after
      every other cigarette/sham, as well as before and after a corticotropin
      stimulation test. The postmenopausal smokers had substantially higher basal
      levels of androstenedione (4.60 +/- 0.42 vs. 2.70 +/- 0.36 nmol/l, P < .05) and
      dihydroepiandrosterone sulfate (2.88 +/- 0.36 vs. 1.91 +/- 0.16 mumol/l, P < .05)
      and higher average levels of cortisol and androstenedione from 0800 to 1300 hr
      (351.0 +/- 17.5 vs. 295.5 +/- 17.1, nmol/l and 3.58 +/- 0.42 vs. 2.51 +/- 0.19
      nmol/l, P = .03, and P < .05, respectively). There were small acute effects of
      individual cigarettes on the hormones, but the response to corticotropin was
      similar in smokers and nonsmokers. Our results indicate that cigarette smoking
      causes a generalized disturbance in adrenal cortical hormone levels. There is no
      evidence for acute tolerance to the adrenocortical affects of the hourly smoking
      of medium-nicotine cigarettes, but these acute effects do not explain the higher
      hormone levels in smokers. There is no evidence for a partial block in the
      cortisol synthesis pathway to explain the increased adrenal androgen levels in
      smokers.

PMID- 7815330
TI  - Ontogeny of nigrostriatal dopamine neuron autoreceptors: iontophoretic studies.
AB  - This study characterized somatodendritic dopamine (DA) autoreceptors on nigral DA
      containing neurons during postnatal developmental in chloral hydrate-anesthetized
      rats. Antidromically activated nigrostriatal DA (NSDA) neurons from 2-week-old
      animals were found to be less sensitive to the inhibitory effects of cumulative
      i.v. doses (1-32 micrograms/kg) of the DA agonists apomorphine (D2/D3/D1) and
      quinpirole (D2/D3) than those from adults. The age-dependent difference in DA
      agonist sensitivity was found to be of significantly greater magnitude for
      apomorphine than for quinpirole. When a single i.p. dose (64 micrograms/kg) of
      apomorphine that elicits a moderate level of inhibition was administered,
      however, no significant differences between the sensitivity of 2-week-old and
      adult NSDA neurons were found. In iontophoretic studies, no age-dependent (1, 2
      and 4 week-olds and adults) differences in nigral DA neuron sensitivity to the
      inhibitory effects of apomorphine, quinpirole and the D3/D2 agonist, 7-hydroxy
      dipropylaminotetralin HBr were found. Iontophoretic studies with the DA
      antagonists, eticlopride (D2/D3) and 7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5
      tetrahydro-1H-3-benzazepine (D1), and i.v. studies with the DA agonists 1-phenyl
      2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol (D1) and N-allyl-1-phenyl-2,3,4,5
      tetrahydro-(1H)-3-benzazepine-7,8-diol (D1) indicate that somatodendritic DA
      autoreceptors on 2-week-old NSDA neurons appear to be of the D2/D3 subtype. These
      results suggest that functional adult-like somatodendritic DA autoreceptors are
      present on nigral DA neurons during early postnatal development. Given the
      conflict between the iontophoretic and i.v. results, however, the nature of any
      potential age-dependent differences in somatodendritic autoreceptor sensitivity
      to DA agonists will need to be examined further in vitro.

PMID- 7815331
TI  - Effects of duloxetine, a new serotonin and norepinephrine uptake inhibitor, on
      extracellular monoamine levels in rat frontal cortex.
AB  - The effects of duloxetine (LY248686), a new inhibitor of serotonin (5
      hydroxytryptamine; 5-HT) and norepinephrine (NE) uptake on extracellular levels
      of NE, 5-HT and dopamine (DA), were studied in the rat frontal cortex and nucleus
      accumbens, using in vivo microdialysis. The oral administration of duloxetine
      (3.125-12.5 mg/kg) produced a dose-dependent increase in the output of both NE
      and 5-HT from the frontal cortex, this increase being maintained throughout the 4
      hr observation period. Chronic administration of duloxetine (6.25 mg/kg, p.o.)
      for 14 days failed to alter basal NE and 5-HT levels in the frontal cortex, but
      augmented the duloxetine-induced increase in output of NE and 5-HT. Amitriptyline
      and maprotiline, administered p.o. at doses of 6.25 to 25 mg/kg, increased NE
      output, but the effect was weaker than that of duloxetine, and neither
      amitriptyline nor maprotiline changed 5-HT output from the frontal cortex.
      Duloxetine, amitriptyline, and maprotiline brought about increases in DA levels
      in the rat frontal cortex, the increase in DA levels induced by duloxetine being
      approximately two or three times more potent than that induced by amitriptyline
      and maprotiline. In the nucleus accumbens, duloxetine also produced a dose
      dependent increase in DA output more potent than that produced by amitriptyline
      and maprotiline. These results show that duloxetine causes a potent and sustained
      increase in the output of both NE and 5-HT in the rat frontal cortex, related to
      its inhibition of NE and 5-HT uptake; these results also show that duloxetine
      increases DA output in the frontal cortex.

PMID- 7815332
TI  - Effects of flecainide, quinidine, and 4-aminopyridine on transient outward and
      ultrarapid delayed rectifier currents in human atrial myocytes.
AB  - Antiarrhythmic drugs prevent atrial reentrant arrhythmias by prolonging atrial
      action potential duration and refractoriness. The ionic mechanisms by which
      antiarrhythmic drugs alter human atrial repolarization are poorly understood. The
      present study was designed to assess the concentration-, voltage-, time- and
      frequency-dependent effects of the antiarrhythmic agents quinidine and
      flecainide, as well as of the K+ channel blocker 4-aminopyridine, on the calcium
      independent transient outward current (Ito1) and the ultrarapid delayed rectifier
      current (IKur) in isolated human atrial myocytes. Quinidine and flecainide
      blocked Ito1 at clinically relevant concentrations. Block of Ito1 by quinidine
      was use and frequency dependent, whereas block by flecainide was frequency
      independent, and 4-aminopyridine showed use-dependent unblocking. Depolarizing
      prepulses enhanced flecainide block and reduced 4-aminopyridine block in a
      fashion suggesting a preferential interaction with the inactivated state for
      flecainide and with the resting, closed state for 4-aminopyridine. Quinidine
      block depended on the potential of a depolarizing test pulse in a fashion
      suggesting open channel block. All three drugs accelerated channel inactivation
      during depolarization at 1 Hz and failed to block Ito1 during initial current
      rise, with block appearing with time constants of 6.3 +/- 1.2 msec for
      flecainide, 14.5 +/- 4.2 msec for quinidine and 3.0 +/- 0.9 msec for 4
      aminopyridine at 16 degrees C, suggesting a role for channel opening in block
      development. Quinidine blocked IKur at clinical concentrations, whereas
      flecainide had no effect on IKur. Quinidine block of IKur was voltage dependent,
      with part of the voltage dependence attributable to open-channel block and the
      remainder compatible with a blocking site within the voltage field at a position
      subject to 23% of the total electrical field. Quinidine's blocking actions on
      IKur were similar to those previously reported for block of a cardiac K+ channel
      clone of the Shaker family (Kv1.5), for which IKur is believed to be the
      equivalent native current. These results indicate that flecainide and quinidine
      block Ito1, and quinidine blocks IKur, in human atrial myocytes in a state
      dependent fashion. Because drug effects are manifest at clinically relevant
      concentrations, and Ito1 and IKur have been shown to be potentially important
      currents in human atrial repolarization, these findings are relevant to
      understanding the ionic mechanisms underlying the clinical antiarrhythmic
      properties of these drugs.

PMID- 7815333
TI  - High-performance liquid chromatography separation of hydroxylated estradiol
      metabolites: formation of estradiol metabolites by liver microsomes from male and
      female rats.
AB  - A high-performance liquid chromatography method has been described for the
      separation of estradiol (E2), estrone (E1) and 27 hydroxylated and keto
      derivatives of these estrogens. Chromatography of a mixture of 29 estrogen
      standards resulted in 20 different peaks. Solvent extraction followed by the
      chromatographic separation and quantification of radioactive metabolites was used
      for studies on the metabolism of [4-14C]E2 by liver microsomes from adult male
      and female rats. Liver microsomes from male rats metabolized [4-14C]E2 more
      rapidly and to a larger number of metabolites than liver microsomes from female
      rats. Under conditions in which less than 10% of the substrate was metabolized,
      major metabolites from liver microsomes of male rats cochromatographed with E1, 2
      OH E2, 15 alpha-OH E2 and 16 alpha-OH E2, and major metabolites from liver
      microsomes of female rats cochromatographed with E1, 2-OH E2 and 16 alpha-OH E2.
      The identity of the metabolites was confirmed by mass spectrometry. Using liver
      microsomes from male rats and conditions in which more extensive metabolism of
      the substrate occurred, more than 15 additional metabolites of [4-14C]E2 were
      observed. Liver microsomes from male rats were many-fold more active than liver
      microsomes from female rats at catalyzing the 2-, 15 alpha- and 16 alpha
      hydroxylation of E2. Our studies on the metabolism of [4-14C]E2 by rat liver
      microsomes indicate that the profile of E2 metabolites is dependent on the time
      of incubation, microsomal protein concentration and substrate concentration.

PMID- 7815334
TI  - Nonpeptide glycoprotein IIb/IIIa inhibitors. 5. Antithrombotic effects of MK
      0383.
AB  - The antiaggregatory and antithrombotic actions of MK-0383, a low molecular
      weight, nonpeptide antagonist of the platelet glycoprotein IIb/IIIa, were
      evaluated in a variety of canine models. Inhibition of ex vivo platelet
      aggregation responses to ADP and collagen were observed after the acute
      sequential i.v. administrations of 10 to 500 micrograms/kg or 360-min continuous
      i.v. infusions of 1 to 10 micrograms/kg/min of MK-0383. Hemostatic function
      normalized within 30 (platelet response to collagen, template bleeding times) to
      90 min (platelet response and sensitivity to ADP) after the termination of 360
      min i.v. MK-0383 infusions, suggesting no protracted, direct effects on platelet
      function. With acute sequential i.v. administrations of MK-0383, platelet
      response to ADP was abolished without significant extension of bleeding time. In
      a model of platelet-dependent cyclic flow reductions in injured, stenosed left
      circumflex coronary artery, the bolus i.v. administrations of 300 and 1000
      micrograms/kg of MK-0383 totally abolished cyclic flow reductions for periods of
      18 +/- 1 and 37 +/- 5 min, respectively. In a model of electrically induced left
      circumflex coronary artery occlusive thrombosis, 10 micrograms/kg/min i.v. of MK
      0383 initiated 15 min before electrical injury prevented occlusive thrombosis in
      three of six preparations despite continued electrical stimulation of the vessel
      for 300 min, delayed occlusion in three of six preparations (160.3 +/- 5.5 min)
      and reduced thrombus mass (5.1 +/- 1.3 mg), compared to the development of
      occlusive thrombosis in six of six saline-treated preparations (50.5 +/- 8.7 min;
      19.1 +/- 3.0 mg). When administered as an adjunct to thrombolytic agents in the
      presence of background heparin for lysis of electrically induced left circumflex
      coronary artery occlusive thrombus, 10 micrograms/kg/min i.v. of MK-0383
      initiated 15 min before tissue-type plasminogen activator or streptokinase
      increased the incidence of (tissue-type plasminogen activator: eight of nine MK
      0383 vs. three of eight saline; streptokinase: eight of eight MK-0383 vs. two of
      eight saline) and accelerated reperfusion, and reduced the incidence of acute
      thrombotic reocclusion during continued MK-0383 infusion. These findings indicate
      significant antithrombotic potential for MK-0383 alone or as an adjunct to
      thrombolytic therapy in the treatment of coronary artery ischemic syndromes.

PMID- 7815335
TI  - Reversal of nerve ligation-induced allodynia by spinal alpha-2 adrenoceptor
      agonists.
AB  - After nerve injury, a sympathetically dependent allodynia may be observed. Spinal
      alpha-2 agonists inhibit preganglionic neurons. The nature of the effect of alpha
      2 agonists on allodynia induced by L5 and L6 nerve ligation (Chung model) was
      thus examined. Rats were implanted with spinal intrathecal catheters directed at
      the upper lumbar (L1-L2) or the lower cervical (C5-C6) spinal levels. After nerve
      injury, rats displayed a tactile allodynia (mean withdrawal thresholds, < 2.3 g).
      Lumbar intrathecal injection of alpha-2, but not alpha-1 or an opiate agonist,
      resulted in a dose-dependent reversal of the allodynia, with the ordering of
      activity (ED50 in micrograms in parentheses) being dexmedetomidine (0.9) >
      oxymetazoline (14) = guanfacine (17) = 5-bromo-6-(2-imidazolin-2
      ylamino)quinoxaline (19) = 2-(2,6-diethylphenylamino)-2-imidazoline (21) =
      clonidine (22) > morphine (> 30) = methoxamine (> 30 micrograms). The effects of
      clonidine and 2-(2,6-diethylphenylamino)-2-imidazoline were reversed by the
      intrathecal injection of yohimbine. At equivalent doses, clonidine delivered
      systemically, i.c.v. by chronic ventricular guides, or at the level of the
      cervical spinal cord, produced substantially less antiallodynic action. These
      results jointly suggest that the sites of the antiallodynic action of spinal
      alpha-2 agonists are located at the level of the spinal preganglionic neurons and
      correspond to their ability to diminish preganglionic sympathetic outflow. The
      failure of morphine to exert an antiallodynic action reflects the fact that 1)
      opiates act presynaptically on small primary afferents and the allodynia is
      mediated by large afferent input and 2) opiates, unlike alpha-2 agonists do not
      have an effect on autonomic outflow.

PMID- 7815336
TI  - In vivo inhibition of endotoxin-induced pro-inflammatory cytokines production by
      the sigma ligand SR 31747.
AB  - In previous studies, the authors demonstrated that the new sigma ligand, cis-N
      cyclohexyl-N-ethyl-3-(3-chloro-4-cyclohexyl-phenyl) propen-2-ylamine
      hydrochloride (SR 31747), elicited a suppressive effect on immune responses
      through the sigma receptor expressed on lymphocytes. Here the effect of SR 31747
      on the proinflammatory cytokine production by endotoxin-activated macrophages is
      examined. In vivo, SR 31747 dramatically blocked lipopolysaccharide-induced
      production of interleukin (IL)-1, IL-6 and tumor necrosis factor-alpha in a dose
      dependent manner (ED50, 2 mg/kg). Whereas SR 31747 suppression was not observed
      in vitro on lipopolysaccharide-induced IL-6 by macrophages, sera from SR 31747
      treated animals displayed a strong inhibitory activity. It was shown that this
      effect could be completely reversed by the steroid receptor antagonist,
      mifepristone, which suggests that SR 31747 probably abrogated monokine production
      through an indirect mechanism that involves endogenous corticosteroids. This
      conclusion was supported by in vivo experiments that showed that 1) ablation of
      corticosteroids by use of mifepristone or adrenalectomy suppressed the effect of
      SR 31747 and 2) administration of SR 31747 induced an enhancement of the
      corticosterone level. It was also shown that this molecule improved the survival
      of animals with endotoxinic shock as a result of monokine inhibition. The
      combination of immunosuppression, previously described, along with anti
      inflammatory properties makes SR 31747 a novel attractive molecule for
      therapeutic applications such as autoimmune diseases in which both immune and
      inflammatory disorders are involved.

PMID- 7815337
TI  - Discriminative stimulus, self-reported and cardiovascular effects of orally
      administered cocaine in humans.
AB  - This study evaluated whether an oral dose of cocaine can serve as a
      discriminative stimulus in humans. Four male and one female cocaine-abusing
      volunteers (ages 26-41 years) were trained to discriminate between cocaine HCl
      (80 mg/70 kg p.o.) and placebo. Once the criterion for discrimination was met
      (i.e., > or = 80% correct responding for four consecutive sessions), dose-effect
      curves were determined for orally administered cocaine (20, 40, 80 and 120 mg/70
      kg), intranasally administered cocaine (20, 40, 80 and 120 mg/70 kg) and the
      benzodiazepine triazolam (0.25 and 0.50 mg/70 kg p.o.). All five subjects met the
      criterion for the cocaine-placebo discrimination within four to seven sessions.
      Novel cocaine doses by either the oral or intranasal route of administration
      generally produced dose-related increases in cocaine-appropriate responding,
      whereas triazolam produced predominantly placebo-appropriate responding. Cocaine
      by both routes produced qualitatively similar increases in stimulant-like self
      reports, blood pressure and heart rate, whereas triazolam produced increases in
      sedative-like ratings and no changes in cardiovascular measures. Throughout dose
      effect curve determinations, the training dose of cocaine and placebo continued
      to be identified correctly in four of five subjects (range, 75-100% correct
      responding). These results suggest that orally administered cocaine (80 mg/70 kg)
      is discriminable from placebo, has behavioral effects that are qualitatively
      similar to intranasal cocaine and does not show cross-generalization to a
      pharmacologically dissimilar compound.

PMID- 7815338
TI  - Carrier-mediated transport mechanism of foscarnet (trisodium phosphonoformate
      hexahydrate) in rat intestinal tissue.
AB  - New findings are presented on the specific transport mechanisms of foscarnet
      (trisodium phosphonoformate hexahydrate) in rat small intestinal tissue and proof
      for the partial participation of the Na(+)-phosphate co-transport system in
      foscarnet transport. The transport of the free acid form of foscarnet,
      phosphonoformic acid (PFA), was studied in rat small intestine by applying Ussing
      chambers. Transport studies in both mucosal (m)-to-serosal (s) and s-to-m
      directions revealed polarization of PFA transport. In m-to-s studies, nonlinear
      concentration-dependent transport was observed and described by the following
      transport parameters (estimate +/- asymptotic standard error): 0.84 +/- 0.13
      mumol/h.cm2, 1.13 +/- 0.29 mM and 0.22 +/- 0.05 cm/h for the maximal transport
      rate (Jmax), the half-maximal transport concentration (Kt) and the passive
      membrane permeability constant (Pm), respectively. PFA transport (1.0 mM) was
      reduced to 72% and to 56% in the presence of the structural analogs phosphate and
      arsenate (10 mM), respectively. Bidirectional transport studies of PFA at 38
      degrees C and 4 degrees C revealed a higher decrease in transport rate for the m
      to-s studies than for the s-to-m studies. The combined results of the experiments
      described in this study demonstrate that PFA transport across rat small intestine
      is partly passive, using both the paracellular and transcellular pathways, and
      partly carrier-mediated, involving the phosphate co-transport system.

PMID- 7815340
TI  - FR121196, a potential antidementia drug, ameliorates the impaired memory of rat
      in the Morris water maze.
AB  - We investigated the effects of FR121196 N-(4-acetyl-1-piperazinyl)-4
      fluorobenzenesulfonamide on the performance of rats in the Morris water maze
      using a two-trial-per-day regimen. Escape latency to find the platform was
      significantly prolonged in young rats subjected to scopolamine (1 mg/kg)
      treatment or to nucleus basalis magnocellularis (NBM) or fimbria-fornix (FF)
      lesioning compared with the respective control animals. Similar memory deficit
      was observed in aged rats (24-26 months old) compared with young rats. Daily
      treatment with FR121196 (0.1-1.0 mg/kg i.p.) ameliorated all the memory deficits
      except in the FF-lesioned rats, whereas physostigmine (0.032-0.32 mg/kg)
      ameliorated the memory deficits in scopolamine-treated rats but not in the NBM
      lesioned, FF-lesioned or aged rats. Methamphetamine (0.32-3.2 mg/kg) hardly
      ameliorated the memory deficits and, rather, aggravated those in the scopolamine
      treated, NBM-lesioned and aged rats. Neurochemical analysis of the brain showed
      that dopamine, norepinephrine and serotonin levels were significantly reduced in
      the hippocampus of the FF-lesioned rats compared with the sham control, and a
      significant reduction of dopamine level in the cortex was also observed in the
      aged rats compared with young rats. None of these parameters were changed after
      NBM lesioning. We concluded that FR121196 ameliorates the memory deficits of rats
      with cholinergic dysfunction through the action on the hippocampal monoaminergic
      (possibly serotonergic) neurons.

PMID- 7815339
TI  - Renal adaptation to altered dietary sulfate in rats.
AB  - Proximal tubular reabsorption is of primary importance in the regulation of the
      homeostasis of inorganic sulfate, an electrolyte that is necessary for
      biosynthetic and detoxification reactions. The objective of the present
      investigation was to determine the effect of dietary sulfate deprivation,
      produced by a diet low in methionine, on the renal transport of sulfate. Female
      Lewis rats were fed a diet containing negligible amounts of sulfate and cystine
      and low in methionine (0.37%) or a control diet (methionine 1.12%, cystine 0.07%)
      for 8 days to examine the urinary excretion rate and renal clearance of sulfate.
      The sulfate excretion rate was decreased by day 4 of the low methionine diet and
      remained low. Both the urinary excretion rates and renal clearance values were
      significantly decreased on day 8 (144 +/- 71 vs. 517 +/- 264 mumol/12 hr in
      controls, mean +/- S.D., n = 7, P < .005 and 0.38 +/- 0.19 vs. 1.07 +/- 0.61 ml
      min-1 kg-1 in controls, n = 5-6, P < .05, respectively), although the serum
      sulfate concentrations were unchanged. In vitro transport studies were performed
      in kidney cortex brush border membrane (BBM) and basolateral membrane vesicles
      isolated from rats fed either the low methionine or control diet for 7 to 9 days.
      The Vmax for BBM sodium/sulfate cotransport was increased in kidneys from animals
      that received the low methionine diet (1.1 +/- 0.10 vs. 0.75 +/- 0.08 nmol mg of
      protein-1 10 sec-1 in controls, n = 5, P < .001); there were no significant
      differences in the Km.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7815341
TI  - Sodium 2,3-dimercaptopropane-1-sulfonate challenge test for mercury in humans:
      II. Urinary mercury, porphyrins and neurobehavioral changes of dental workers in
      Monterrey, Mexico.
AB  - The sodium salt of 2,3-dimercaptopropane-1-sulfonic acid (DMPS) challenge test
      (300 mg p.o. after an 11-hr fast) was given in Monterrey, Mexico to dental and
      nondental personnel. Urine samples were collected and analyzed for total mercury.
      The mean mercury urinary excretion (+/- S.E.) for 6 hr before and 6 hr after DMPS
      administration for 10 dental technicians, who formulate amalgam, was 4.84
      micrograms +/- 0.742 and 424.0 micrograms +/- 84.9; for 5 dentists, who use
      amalgam in their practice, 3.28 micrograms +/- 1.11 and 162.0 micrograms +/-
      51.2; and for 13 nondental personnel, 0.783 microgram +/- 0.189 and 27.3
      micrograms +/- 3.19. The urinary coproporphyrin levels before DMPS
      administration, which are indicative of renal mercury content, were
      quantitatively associated with the urinary mercury levels among the three study
      groups after DMPS administration. This was not so if the urinary mercury level
      before DMPS administration was compared with the urinary coproporphyrin
      concentration. The urinary mercury level after DMPS administration is a better
      indicator of exposure and renal mercury burden than is the mercury level measured
      in the urine before DMPS is given. Regression analysis showed that the
      coefficient of urinary mercury was statistically and adversely associated with
      complex attention (switching task), the perceptual motor task (symbol-digit
      substitution), symptoms and mood. The easily performed DMPS-mercury challenge
      test is useful for monitoring dental personnel for mercury vapor exposure.

PMID- 7815342
TI  - Dose- and duration-dependent tolerance to rotational effects of apomorphine in a
      rat model of Parkinsonism.
AB  - We sought to determine what temporal and dose factors influence the development
      of tolerance to dopaminergic agents in parkinsonism. Apomorphine was administered
      at varying doses and durations to rats with unilateral 6-hydroxydopamine-induced
      nigrostriatal lesions and rotational behavior was monitored. Ten rats were
      studied across seven daily, intermittent treatment sessions, during which four
      equal boluses of apomorphine were injected at 1- to 2-hr intervals; increasing
      doses were used on different days. The total number of rotations were reduced by
      approximately 25% after repeated 0.8- and 3.2-mg/kg doses, but not after doses
      ranging from 0.1 to 0.4 mg/kg; neither the peak rate nor the duration of
      responses were altered. Nine other, untreated rats received four, 0.8-mg/kg
      boluses of apomorphine and did not exhibit any decrement in response. An 8-hr
      constant treatment (0.2-mg/kg boluses every 10 min) resulted in a 70% reduction
      in rotational response; plasma levels remained stable in five unlesioned rats who
      underwent a similar constant treatment. These results suggest that tolerance to
      dopaminergic stimulation is more apt to develop with constant than with
      intermittent treatment and that tolerance may require previous drug exposure in
      order to occur. Optimal treatment of patients with severe parkinsonism may
      require periods without dopaminergic effect in order to maintain drug response.

PMID- 7815343
TI  - Peripheral beta adrenergic blockade modifies airpuff startle-induced heart rate
      responses.
AB  - Prior studies showed that repeated airpuff startle-reaction stimuli applied to
      normotensive inbred Wistar-Kyoto rats bred in La Jolla or Sprague-Dawley rats
      elicit pressor responses on all trials except trial-dependent bradycardia or
      tachycardia. However, hypertensive inbred spontaneously hypertensive rats bred in
      La Jolla exhibited no bradycardia. Peripheral methylatropine blocked bradycardia
      and unmasked tachycardia, which implies concurrent autonomic discharges on early
      trials. As shown here, vendor inbred Wistar-Kyoto rats from Charles River
      Laboratories (WKYCR) fail to show bradycardia. Because stress-induced
      parasympathetic responses are important to understanding arrhythmogenesis, we
      tested whether (WKYCR) and inbred spontaneously hypertensive rats from Charles
      River Laboratories (SHRCR) exhibit any parasympathetic activation by blunting
      sympathetic chronotropic responses with cardioselective beta-adrenoceptor
      antagonists. WKYCR or SHRCR were pretreated with either nonselective propranolol,
      beta 1-selective metoprolol, beta 1-selective celiprolol (with beta 2-receptor
      agonist activity) or ICI 118,551, a selective beta 2-receptor antagonist. Neither
      propranolol nor metoprolol affected resting HR in WKYCR, but both decreased HR in
      SHRCR, whereas celiprolol raised resting HR only in WKYCR. Although control WKYCR
      nor SHRCR exhibited bradycardia, bradycardia was unmasked in both by all beta 1
      selective agents but not by ICI 118,551. However, ICI 118, 551 reduced
      tachycardia responses over all trials in WKYCR, which suggests beta 2
      adrenoceptor involvement in the stress-induced tachycardia. Significant cardiac
      contributions to the pressor responses in both WKYCR and SHRCR were
      found.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7815344
TI  - Calcium modulation of morphine analgesia: role of calcium channels and
      intracellular pool calcium.
AB  - Calcium (Ca++) administered into the i.c.v. space of mice has been reported to
      block opioid-induced antinociception dose dependently. These studies were
      conducted to test the hypothesis that Ca++ i.c.v. blocks the antinociceptive
      effects of morphine i.c.v. as a consequence of transmembrane Ca++ influx and Ca++
      release from intracellular pools. Mice were injected with voltage-sensitive Ca++
      channel antagonists at a dose that did not affect morphine antinociception to
      determine whether this pretreatment would prevent the inhibitory effects of Ca++.
      Nimodipine (12 nmol i.c.v.) was ineffective in preventing the inhibitory effects
      of Ca++ (100 nmol i.c.v.), whereas omega-conotoxin GVIA (3.3 pmol i.c.v.)
      completely prevented the inhibition by Ca++ of morphine antinociception. Other
      experiments were conducted to determine whether blocking Ca++ release from
      Ca++/caffeine-sensitive microsomal pools with ryanodine would prevent the
      inhibitory effects of Ca++. Ryanodine (2 nmol i.c.v.) significantly attenuated
      the inhibition by Ca++ of morphine antinociception. Another hypothesis to be
      tested was that stimulation of Ca++ release from intracellular pools would, like
      Ca++, block morphine antinociception. Thapsigargin (0.002-30 nmol i.c.v.), which
      increases cytosolic Ca++ by depleting Ca++ from inositol 1,4,5-trisphosphate
      sensitive microsomal pools, dose-dependently blocked the antinociceptive effects
      of morphine. The results of this study indicate that Ca++ blocked morphine
      antinociception by stimulating Ca++ influx through omega-conotoxin GVIA-sensitive
      channels and by stimulating Ca++ release from Ca++/caffeine-sensitive microsomal
      pools.

PMID- 7815345
TI  - 7-Chloro-3-methyl-3-4-dihydro-2H-1,2,4 benzothiadiazine S,S-dioxide (IDRA 21): a
      benzothiadiazine derivative that enhances cognition by attenuating DL-alpha-amino
      2,3-dihydro-5-methyl-3-oxo-4-isoxazolepropanoic acid (AMPA) receptor
      desensitization.
AB  - 7-Chloro-3-Methyl-3-4-Dihydro-2H-1,2,4 Benzothiadiazine S,S Dioxide (IDRA 21),
      which attenuates the rapid autodesensitization of DL-alpha-amino-2,3-dihydro-5
      methyl-3-oxo-4-isoxazolepropanoic acid (AMPA)-selective glutamate receptors and
      increases excitatory synaptic strength, improves cognition (learning and memory),
      as revealed by its ability to improve performance in water maze and passive
      avoidance tests in rats. Normal rats trained to (15-20 sec) reach the exit
      platform rapidly in a water maze that included four incorrect choices were given
      oral IDRA 21 (4-120 mumol/kg) or vehicle and then exposed to a delayed retention
      trial in a maze that included seven incorrect choices. In this retention trial,
      the IDRA 21-treated rats performed considerably better than those that received
      the vehicle. Moreover, oral IDRA 21 (ED50 = 7.6 microM) attenuated the
      performance impairment induced by the AMPA receptor antagonist 2,3-dihydroxy-6
      nitro-7-sulfamoylbenzo (F) quinoxaline in the water maze test. In this test and
      in a passive avoidance test, the performance impairment elicited by alprazolam, a
      full allosteric modulator at gamma-aminobutyric acid-A receptors, or by
      scopolamine, a competitive muscarinic receptor antagonist, was also reduced by
      oral administration of IDRA 21 (ED50 = 13 and 108 mumol/kg, against alprazolam
      and scopolamine, respectively); in all these tests, IDRA 21 was 20- to 30-fold
      more potent than aniracetam. Because IDRA 21 is a racemic molecule; the two
      stereoisomers were isolated and studied behaviorally. Only the (+) form was found
      to be behaviorally active. These results indicate that IDRA 21 given orally to
      rats presumably crosses the blood-brain barrier and acts stereoselectively on
      specific receptors that were operative during this behavioral procedure. Because
      the activity of IDRA 21 on rat cognition tests appears to be related to its
      ability to potentiate AMPA-activated currents, one can suggest that IDRA 21
      improves cognition by acting on a stereoselective site of AMPA receptor that is
      operative in attenuating the rapid autodesensitization of these receptors.

PMID- 7815346
TI  - Modulation of cannabinoid-induced antinociception after intracerebroventricular
      versus intrathecal administration to mice: possible mechanisms for interaction
      with morphine.
AB  - Dose-effect curves were generated for the cannabinoids [intracerebroventricularly
      (icv.)] and compared with those previously generated after administration
      intrathecally (i.t.). The ED50 values after administration of levonantradol, CP
      55,940, delta 9-THC and delta 8-THC i.t. vs. icv. did not differ significantly.
      CP 56,667 was significantly more potent after icv. administration than i.t.
      administration, and was nearly 10 times more potent than CP 55,940 (icv.). CP
      55,940 and CP 56,667, which did not produce greater than additive effects in
      combination with morphine when the drugs were administered i.t., shifted the
      morphine (icv.) dose-effect curve in a parallel manner nearly 10-fold after icv.
      administration. The antinociceptive effects of the cannabinoids (icv.) were not
      blocked by ICI 174,864 (20 micrograms/mouse), nor-BNI (70 micrograms/mouse) or
      naloxone (20 micrograms/mouse or 10 mg/kg s.c.). Pertussis toxin pretreatment
      i.t. for 7 days totally abolished the antinociception produced by the
      cannabinoids (icv. and i.t.). Pretreatment of the mice with forskolin (i.t.) or
      Cl-cAMP (10 micrograms/mouse i.t.), which produced no antinociception,
      significantly attenuated the antinociception produced by the delta 9-THC and CP
      55,940. However, when administered icv., forskolin and Cl-cAMP produced
      antinociception, but did not block or produce greater than additive effects with
      the antinociception produced by the cannabinoids administered icv. The i.t.
      administration of calcium and calcium modulators failed to alter the
      antinociception produced by the i.t. administration of the cannabinoids.
      Conversely, calcium (icv.) blocked the antinociceptive effects of the
      cannabinoids. The AD50 values (+/- CL) for calcium-induced block of delta 9-THC,
      delta 8-THC and CP 55,940 were 215 (94-489), 176 (122-253) and 123 (81-186)
      nmol/mouse, respectively. omega-Conotoxin (1 micrograms/mouse icv.), which did
      not alter the antinociceptive effects of delta 9-THC, significantly reversed the
      calcium-induced blockade of delta 9-THC. Thapsigargin (icv.) blocked the
      antinociception produced by delta 9-THC and CP 55,940. Apamin, blocker calcium
      gated potassium channels, produced a parallel rightward shift in the dose-effect
      curves of delta 9-THC, delta 8-THC and CP 55,940 (i.t.). However, apamin (5
      ng/mouse icv.) failed to block icv. administered cannabinoids. Because acute
      administration of opiates/opioids have been shown to interact with Gi/o protein
      coupled receptors, decrease calcium entry to and content of neurons, reduce cAMP
      levels and produce hyperpolarization of neurons via both ATP- and apamin
      sensitive potassium channels, these three intracellular systems may be common
      points of interaction with the cannabinoids.

PMID- 7815347
TI  - Properties of delta opioid receptor in neuroblastoma NS20Y: receptor activation
      and neuroblastoma proliferation.
AB  - Neuroblastoma NS20Y cells possess a high density of stereoselective delta opioid
      receptors as determined by competition binding with 3H-diprenorphine and various
      opioid ligands. Scatchard analysis of [3H]diprenorphine saturation binding data
      revealed a Kd = 0.79 +/- 0.17 nM and Bmax = 370 +/- 50 fmol/mg protein. These
      opioid binding sites have highest affinity for delta opioid receptor selective
      agonists and lowest affinity for mu opioid receptor selective agonists. Agonist
      binding was sensitive to the presence of the monovalent cation, Na+. Activation
      of receptor with D-Ala2, D-Leu5-enkephalin (DADLE) resulted in dose-dependent
      inhibition of forskolin-stimulated intracellular [3H]cAMP accumulation, which was
      antagonized by (-)-naloxone but not (+)-naloxone. Relative potencies of various
      opioid agonists to inhibit intracellular cAMP production paralleled those
      observed in neuroblastoma x glioma NG108-15 hybrid cells. Pretreatment of NS20Y
      cells with pertussis toxin (PTX) eliminated opioid agonist inhibition of adenylyl
      cyclase activity. Chronic DADLE treatment resulted in desensitization and down
      regulation of opioid receptor. An increase in intracellular [3H]cAMP level above
      the control was observed in the presence of naloxone after chronic DADLE
      treatment. Therefore, opioid binding sites in neuroblastoma NS20Y cells possess
      properties of the classical delta opioid receptor type. After neuroblastoma NS20Y
      was growth arrested by culturing the cells in serum-free medium for 72 hr,
      proliferation was reinitiated by addition of fetal calf serum (FCS), 0.01% to
      12%, and was monitored by either [3H]thymidine incorporation or by dye viability
      assay. It was demonstrated that naloxone and naltriben but not Met5-enkephalin
      could attenuate FCS-induced proliferation in a dose-dependent manner. Naltriben
      was 54-fold more potent than naloxone to attenuate NS20Y proliferation. The
      maximal level of viable cells per well was reduced (35.2 +/- 1.9%) with no
      alteration in FCS concentration-dependent stimulation of growth. Similar
      inhibition by naloxone (37.3 +/- 2.7%) was observed with [3H]thymidine
      incorporation studies. This naloxone effect was serum concentration-dependent and
      could be blocked by culturing NS20Y cells in the presence of both naloxone and
      Met5-enkephalin. Although pretreatment of NS20Y cells with pertussis toxin could
      attenuate FCS-stimulated proliferation, naloxone effect on growth was not
      affected by pertussis toxin pretreatment. Furthermore, the naloxone effect was
      not NS20Y specific. A similar naloxone effect was observed with neuroblastoma
      N1E115, although not with neuroblastoma x glioma NG108-15, nor human
      neuroblastoma SHSY5Y, cell lines that have been reported to contain delta opioid
      receptors. Therefore, activation of delta opioid receptor could modulate FCS
      induced growth in some but not all neuroblastoma cell lines.

PMID- 7815348
TI  - Vasorelaxant and second messenger effects of maxadilan.
AB  - Maxadilan is a potent vasodilator isolated from salivary gland extracts of the
      sand fly. Although cutaneous vasodilatation is probably the most important
      physiologic effect of maxadilan (i.e., assisting the sand fly in obtaining a
      blood meal), it also has effects on other vascular beds. In rabbit isolated
      aorta, recombinant maxadilan exhibited endothelium-independent relaxations with
      an IC50 of 24 nM for norepinephrine-induced (1 microM) contractions. Synthetic
      maxadilan had one-third the potency, with a corresponding IC50 of 74 nM for
      norepinephrine-induced (1 microM) contractions. Pretreatment with a number of
      receptor and channel blockers, including tetraethylammonium (1 mM), glyburide (1
      microM), barium (0.5 mM), indomethacin (10 microM), propranolol (10 microM),
      cimetidine (10 microM) and nifedipine (10 microM) did not affect maxadilan
      induced relaxations. After treatment with maxadilan, contractions recurred very
      slowly over approximately 40 min. At a concentration of 1 microM, maxadilan
      induced a 2- to 3-fold increase in cellular cyclic AMP levels. Maxadilan's
      activity was selective according to vessel type, with maximal activity in rabbit
      aorta and mesenteric artery and no activity in porcine and bovine coronary
      arteries. These studies suggest that maxadilan acts by raising the intracellular
      levels of cyclic AMP in the smooth muscle of selected blood vessels.

PMID- 7815349
TI  - Systemically administered cocaine selectively enhances long-latency responses of
      rat barrel field cortical neurons to vibrissae stimulation.
AB  - Prominent among cocaine's psychostimulant actions are its abilities to heighten
      awareness of the sensory surround and induce sensory hallucinations. Although
      many studies have examined the cellular actions of cocaine in "reward" circuits
      of the brain, few have investigated the impact of cocaine on neuronal function in
      primary sensory circuits. The goal of this study was to characterize the effects
      of cocaine on somatosensory cortical neuronal responsiveness to peripheral
      activation of afferent synaptic pathways. Extracellular recordings were obtained
      from spontaneously active single units in the barrel field cortex of halothane
      anesthetized rats. The spontaneous firing rate and cellular responses to
      mechanical displacement of a single whisker on the contralateral face were
      monitored before and after systemic administration of cocaine (0.25, 0.5, 1.0 and
      2.0 mg/kg i.v.). Control responses to whisker stimulation consisted of an initial
      excitatory burst (E1), a postexcitatory suppression of activity (I) and a
      secondary excitatory discharge (E2). Cocaine effects on spontaneous discharge
      were minimal at low doses up to and including 1.0 mg/kg, whereas suppression of
      spontaneous activity was observed at doses above 2.0 mg/kg. After cocaine
      injection, E1 responses were unchanged or within +/- 30% of control; however, E2
      responses were routinely enhanced 50% to 600% above control levels. I responses
      were increased in magnitude and/or duration. Such facilitation of E2 and I
      responses was observed at doses as low as 0.25 mg/kg but most consistently at
      doses of 0.5 to 1.0 mg/kg. Suppression of evoked responses was observed at doses
      above 2.0 mg/kg. Cocaine's effects on spontaneous and evoked discharge were rapid
      in onset. Peak effects occurred at 6 min postinjection and recovery to control
      patterns of discharge were observed by 20 min postinjection. These results
      indicate that cocaine consistently exerts a facilitating effect on specific late
      components of cortical neuron responses to sensory stimuli. Although the neural
      substrates responsible for this effect have not been identified, such findings
      demonstrate a clear effect of cocaine on sensory signal transmission at dosages
      that can support behavioral reinforcement.

PMID- 7815350
TI  - Hypotensive and natriuretic effects of RB 105, a new dual inhibitor of
      angiotensin converting enzyme and neutral endopeptidase in hypertensive rats.
AB  - Neutral endopeptidase (NEP) is involved in the metabolism of atrial natriuretic
      peptide (ANP), whereas angiotensin-converting enzyme (ACE) is involved in the
      metabolism of angiotensin I; both enzymes participate in bradykinin metabolism.
      RB 105 is a new dual inhibitor which inhibits both peptidases, NEP (Ki = 1.7 nM)
      and ACE (Ki = 4.2 nM). In conscious spontaneously hypertensive rats (SHR), RB 105
      i.v. dose-dependently decreased blood pressure and dose-independently caused
      natriuresis with dose-dependent increases in urinary cGMP and plasma renin
      concentration, and decrease in plasma ACE activity. RB 105 increased urinary
      excretion of both immunoreactive ANP and bradykinin. RB 105 completely blocked
      the hypertensive response of exogenous angiotensin I. Furthermore, RB 105
      potentiated the hypotensive and natriuretic response to ANP and potentiated the
      hypotensive responses of bradykinin in SHR. Intravenous RB 105 decreased blood
      pressure similarly in DOCA-salt, renovascular (1C-2K) and spontaneously
      hypertensive rats and induced a similar natriuretic response in these three
      different renin-dependent and -independent models of hypertension. RB 105 also
      had hypotensive and natriuretic effects in normotensive rats. RB 105 also induced
      an increase in urinary excretion of cGMP and bradykinin and in plasma renin
      concentration in hypertensive and normotensive rats. In conclusion, RB 105 is a
      new dual inhibitor of ACE and NEP able to target both blood pressure and renal
      sodium handling in different experimental renin-dependent and -independent models
      of hypertension.

PMID- 7815351
TI  - Relationship between pharmacokinetics and the analgesic effect of ketorolac in
      the rat.
AB  - The relationship between the pharmacokinetic properties and the analgesic effect
      of ketorolac was evaluated with the pain-induced functional impairment model in
      the rat. Female Wistar rats were injected with uric acid in the knee of the right
      hind limb to produce dysfunction. Then, animals received an oral dose of 0.3, 1,
      1.8, 3.2 or 5.6 mg/kg of ketorolac tromethamine and analgesic effect and blood
      concentration, determined by high-performance liquid chromatography, were
      evaluated at selected times for a period of 4 hr. Ketorolac produced a dose
      dependent analgesic effect, measured as a recovery of the functionality of the
      injured limb, which reached its maximal effect at doses of 3.2 mg/kg or higher.
      When functionality index was plotted against ketorolac blood concentration, a
      direct relationship was observed that was well described by the sigmoidal maximal
      effect model. The data strongly suggest that ketorolac's analgesic effect depends
      on the blood concentration of the drug.

PMID- 7815352
TI  - Nitric oxide and prostaglandins in regulation of acid secretory response in rat
      stomach following injury.
AB  - The gastric mucosa responds to taurocholate (TC) by significantly decreasing acid
      secretion. We examined the role of nitric oxide (NO) in this phenomenon in
      comparison with endogenous prostaglandins. A rat stomach was mounted in an ex
      vivo chamber and perfused with saline, and the potential difference, luminal pH
      and acid responses were measured before and after the application of 20 mM TC for
      30 min with or without pretreatment with the NO synthase inhibitor NG-nitro-L
      arginine methyl ester (L-NAME) or the cyclooxygenase inhibitor indomethacin.
      Exposure of the stomach to TC caused a reduction in potential difference, a
      decrease in acid secretion and an increase in luminal HCO3-. Pretreatment with L
      NAME or indomethacin did not affect potential difference and HCO3- responses, but
      it significantly attenuated the decrease in acid secretion caused by TC. The
      effect of L-NAME was more potent than that of indomethacin, and, especially in
      the presence of L-NAME, acid secretion was actually enhanced after exposure to
      TC. Aminoguanidine, the selective inhibitor of inducible NO synthase, did not
      have any significant effect on either parameter. This effect of L-NAME was
      antagonized by the simultaneous administration of L-arginine but not by that of D
      arginine, whereas the effect of indomethacin was reversed by PGE2. Acid secretion
      in normal stomachs was significantly reduced by nitroprusside and PGE2 but was
      not affected by either L-NAME or indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7815353
TI  - Effect of alpha adrenergic agonist on the rabbit ear artery contraction to
      serotonin: enhanced response mediated by serotonergic1-like receptors.
AB  - The effect of methoxamine or phenylephrine (PHE) on the contractile response of
      the rabbit ear artery to serotonin was assessed by using isolated arterial rings
      mounted in tissue baths for the measurement of isometric force development. A
      contractile threshold concentration of methoxamine or PHE (10-30 nM) shifted the
      serotonin concentration-response curve to the left by approximately 200-fold.
      Neither mechanical removal of the vascular endothelium nor chemical denervation
      had any effect on the alpha agonist-amplified response of ear artery to
      serotonin. Although the response to serotonin in the absence of the alpha agonist
      was mediated primarily by alpha-1 adrenergic receptors, prazosin did not block
      the amplified response to serotonin. Ketanserin (10 nM), ritanserin (50 nM) and
      MDL 72222 (1 microM) also had no effect on the amplified response, ruling out the
      involvement of serotonergic (5-HT)2 and 5-HT3 receptors. However, methiothepin (3
      nM) and 1-(1-naphthyl)piperazine (10 and 100 nM) blocked the PHE-amplified
      contraction of ear artery to serotonin. When the contractile response of ear
      artery to 5-carboxamidotryptamine was measured in the presence of a threshold
      concentration of alpha agonist, the concentration-response curve was shifted 8300
      fold to the left. The amplified response to 5-carboxyamidotryptamine was
      insensitive to 10 nM ketanserin, but was blocked by 3 nM methiothepin.
      Sumatriptan, a selective 5-HT1 agonist, failed to induce vasoconstriction in the
      absence of a threshold concentration of alpha agonist. However, in the presence
      of PHE, sumatriptan induced a concentration-dependent contraction.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7815354
TI  - Distribution of VIP binding sites in opossum internal anal sphincter circular
      smooth muscle.
AB  - The main goal of the present study was to determine whether vasoactive intestinal
      polypeptide (VIP) binds exclusively to smooth muscle plasma membranes or also to
      neurons. We examined the distribution of VIP binding sites in different fractions
      and subfractions of smooth muscle membranes prepared from the circular muscle
      layer of opossum internal anal sphincter (IAS). The markers used for synaptosomal
      and smooth muscle plasma membranes were [3H]saxitoxin binding and 5' nucleotidase
      activity, respectively. Fractionation of the membranes was carried out by
      differential centrifugation of the circular smooth muscle membranes. Further
      subfractionations were done by sucrose density gradient centrifugation. VIP
      binding was high in the membrane fractions that were enriched with 5'
      nucleotidase activity. However, some VIP binding was also found in fractions with
      high saxitoxin binding. Membranes prepared from isolated smooth muscle cells and
      myenteric neurons both had high VIP binding. Membranes prepared from isolated
      smooth muscle cells displayed higher 5' nucleotidase activity, whereas membranes
      prepared from isolated myenteric plexi had higher saxitoxin binding. In
      conclusion, in the opossum IAS circular smooth muscle, binding of VIP occurs on
      both the smooth muscle plasma membranes and the synaptosomal membranes. The
      presence of VIP binding sites on the smooth muscle plasma membrane supports the
      role of VIP as an inhibitory neurotransmitter. The significance of binding of the
      neuropeptide to the neuronal membranes remains to be determined.

PMID- 7815356
TI  - 5-Aminosalicylic acid abrogates T-cell proliferation by blocking interleukin-2
      production in peripheral blood mononuclear cells.
AB  - The antiinflammatory agent sulfasalazine (SS) is prescribed to treat Crohn's
      disease, ulcerative colitis and rheumatoid arthritis. Activated T cells are
      present within diseased mucosal and synovial sites. We tested whether SS or its
      metabolites 5-aminosalicylic acid (5-ASA) and sulfapyridine (SP) inhibited the T
      cell activation products interleukin 2 (IL-2) and interleukin 2 receptor alpha
      chain (IL-2R alpha). Experiments were performed in phytohemaglutinin- and phorbol
      ester-stimulated peripheral blood mononuclear cells. Radioactive thymidine and
      leucine incorporation assayed DNA and protein synthesis, respectively. Enzyme
      linked immunosorbent assay and Northern blot analysis measured IL-2 and IL-2R
      alpha. Lactate dehydrogenase release determined cell viability, and intracellular
      free calcium was measured by an indole fluorescent indicator. SS and 5-ASA, but
      not SP, inhibited T-cell proliferation and protein synthesis in phytohemaglutinin
      and phorbol ester-stimulated peripheral blood monomuclear cells. 5-ASA (625
      microM) markedly reduced culture supernatant IL-2 protein levels by 92% and
      steady-state IL-2 messenger RNA levels 4.4-fold at 24 and 18 hr, respectively.
      The supplementation of IL-2 restored T-cell proliferation only in 5-ASA-treated
      cultures. SS, 5-ASA and SP did not alter intracellular calcium accumulation after
      mitogenic stimulation. SS and 5-ASA (625 microM) caused 71% and 37% cytotoxicity,
      respectively, in 72-hr cultures. 5-ASA inhibits T-cell proliferation in part by
      blocking IL-2 messenger RNA accumulation and protein production downstream of the
      rise in cytosolic calcium. Inhibition of IL-2 production is an additional
      mechanism of action for 5-ASA.

PMID- 7815355
TI  - Prolonged microvascular vasodilation induced by leukotriene B4 in human skin is
      cyclooxygenase independent.
AB  - When the potent chemoattractant leukotriene B4 (LTB4) is applied topically to
      human skin it causes delayed onset, long-lasting leukocyte accumulation and
      erythema. We investigated the role of prostaglandins in the increase in local
      blood flow by applying LTB4 topically to the forearm skin of 22 healthy male
      volunteers and measuring the effect of the anti-inflammatory compounds tenidap,
      naproxen and indomethacin. Local microvascular blood flow responses were measured
      by laser Doppler flow probe and planimetry. LTB4 induced dose-dependent increases
      in blood flow which were maximal at 48 hr and lasted 4 days. Laser Doppler flow
      (% flux) at 48 hr was 2.7 +/- 0.1, 20.6 +/- 3.1, 28.7 +/- 2.4 and 30.2 +/- 2.3%
      in control and 3, 10, 30 ng/site LTB4, respectively (mean +/- S.E.M.). In eight
      subjects the intradermal injection of indomethacin, at a dose (3 x 10(-9)
      mol/site) that inhibited significantly the increased flow induced by
      intradermally injected arachidonic acid (1 x 10(-9) mol/site, n = 6), had no
      effect on the increased skin blood flow response induced by LTB4 (10 ng/site) at
      48 hr. Blood flow in vehicle-injected LTB4 sites was 810 +/- 150% above basal and
      819 +/- 149% in sites injected with indomethacin. In 20 subjects, the effect of
      the anti-inflammatory drugs naproxen and tenidap given orally on the skin blood
      flow responses to LTB4 were compared in a double-blind crossover design. The 1085
      +/- 98% increase in local blood flow induced by 30 ng of LTB4 at 48 hr was
      unaltered at the end of the treatment periods with either naproxen or tenidap,
      where blood flow in the LTB4-treated sites was increased 1018 +/- 131% and 1034
      +/- 130%, respectively. Because the vasodilator response to exogenous LTB4 was
      not altered by nonsteroidal anti-inflammatory drugs either injected locally or
      taken orally, we suggest that endogenous prostaglandins are not involved in this
      response.

PMID- 7815357
TI  - Role of metabolism by esterase and cytochrome P-450 in cocaine-induced
      suppression of the antibody response.
AB  - To investigate the role of metabolism in cocaine-induced immunosuppression,
      diazinon and beta-ionone were administered as an esterase inhibitor and a
      cytochrome P-450 (P-450) inducer, respectively, to B6C3F1 female mice. When 10 or
      30 mg/kg of diazinon was administered 30 min before cocaine (30 mg/kg) was
      administered i.p. for 7 consecutive days, the suppression of the T-dependent
      antibody response to sheep red blood cells was potentiated greatly when compared
      to the suppression by cocaine alone. Spleen and thymus weights were decreased
      significantly and serum glutamate-pyruvate transaminase activities were elevated
      dramatically when cocaine and diazinon were administered together. beta-Ionone
      was administered s.c. for 7 consecutive days and the P-450 activities were
      determined 3 days after the last administration. beta-Ionone induced cocaine N
      demethylation, which is the first step in the activation of cocaine to the
      metabolites capable of producing hepatotoxicity, as well as P-450IA1- and P
      450IIB1-specific monooxygenases. The inductive effects of beta-ionone on P
      450IA1/2 and P-450IIB1/2 proteins were confirmed by using Western immunoblotting
      with selective monoclonal antibodies. In addition, when beta-ionone (600 mg/kg)
      was administered with cocaine for 7 days, the suppression of the antibody
      response was potentiated greatly, thymus weight was decreased significantly and
      serum glutamate-pyruvate transaminase was elevated. Our present results suggest
      that inhibition of the esterase pathway of cocaine shunts the metabolism of
      cocaine into an immunotoxic pathway, and that the metabolism of cocaine by P-450
      may be the critical pathway for the generation of the metabolites capable of
      suppressing the antibody response.

PMID- 7815358
TI  - BPC-15 reduces trinitrobenzene sulfonic acid-induced colonic damage in rats.
AB  - The effect of BPC-15 (Booly Protection Compound-15) was evaluated in a rat model
      of colonic injury. A single intracolonic administration of trinitrobenzene
      sulfonic acid (TNBS) dissolved in ethanol induces severe colonic damage, which is
      characterized by areas of necrosis surrounded by areas of acute inflammation. The
      damage is associated with high myeloperoxidase (MPO) activity, mainly as a
      reflection of neutrophilic infiltration into the damaged tissue. In this study, 1
      hr before a single intracolonic administration of 50 mg/kg of TNBS in 50%
      ethanol, the animals were treated with one of the following doses of BPC-15:
      0.0001, 0.001, 0.01, 0.1, 1 or 10 nmol/kg administered i.p. or with a dose of 10
      nmol/kg administered intracolonically. The animals were sacrificed 3 days later
      and the extent of colonic necrosis and hyperemia was measured with an image
      analyzer. The i.p. administration of BPC-15 significantly reduced the extent of
      TNBS-induced colonic damage in a dose-dependent manner. This was associated with
      a statistically significant and dose-dependent reduction in colonic tissue MPO
      activity. At the dose tested (10 nmol/kg), intracolonic administration of BPC-15
      did not significantly reduce either the extent of the colonic damage or the
      increase in MPO activity induced by TNBS. In conclusion, this study showed that
      i.p. administration of BPC-15 reduced TNBS-induced colonic damage in rats.

PMID- 7815360
TI  - 4-(2'-Methoxy-phenyl)-1-[2'-(n-2"-pyridinyl)-p-iodobenzamido]-ethyl- piperazine
      ([125I]p-MPPI) as a new selective radioligand of serotonin-1A sites in rat brain:
      in vitro binding and autoradiographic studies.
AB  - Binding characteristics of a radioiodinated serotonin-1A (5-HT1A) receptor
      antagonist, 4-(2'-methoxy-phenyl)-1-[2'-(n-2"-pyridinyl)-p- iodobenzamido]-ethyl
      piperazine ([125I]p-MPPI) were evaluated using in vitro homogenate binding and
      autoradiographic techniques in rat brains. [125I]p-MPPI displayed a Kd value of
      0.32 +/- 0.04 nM (in the presence of MgCl2) and a Bmax value of 315 +/- 60
      fmol/mg of protein in rat hippocampal homogenates. The number of 5-HT1A receptors
      labeled by [125I]p-MPPI was 40% higher than that labeled by trans-8-hydroxy-2-(N
      n-propyl-N-3'-iodo-2'- propenyl)aminotetralin ([125I]R(+)8-OH-PIPAT) (225 +/- 47
      fmol/mg of protein), a radioiodinated 5-HT1A agonist. The magnesium ion showed an
      inhibitory effect on [125I]p-MPPI binding but increased the specific binding of
      [125I]R(+)8-OH-PIPAT. A significant increase in Bmax values in the presence of
      guanyl nucleotides was observed for [125I]p-MPPI (control, 307 +/- 35 fmol/mg of
      protein; with GTP, 345 +/- 30 fmol/mg of protein; with guanylyl-imidodiphosphate,
      362 +/- 35 fmol/mg of protein); however, both guanyl nucleotides significantly
      reduced the Bmax values measured by [125I]R(+)8-OH-PIPAT (control, 213 +/- 50
      fmol/mg of protein; with GTP, 133 +/- 20 fmol/mg of protein; with guanylyl
      imidodiphosphate, 108 +/- 20 fmol/mg of protein). The binding characteristics of
      [125I]p-MPPI for 5-HT1A receptors suggest that p-MPPI is an antagonist for 5-HT1A
      receptors. In vitro autoradiographic studies in rat brain sections with [125I]p
      MPPI showed specific labeling of areas rich in 5-HT1A receptors and the regional
      distribution closely matched those labeled by [125I]R(+)8-OH-PIPAT.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7815359
TI  - Characterization of the cloned human mu opioid receptor.
AB  - Opioid drugs exert a wide spectrum of physiological and behavioral effects,
      including effects on pain perception, mood, motor control and autonomic
      functions. The effects of opioids are mediated via a family of membrane-bound
      receptors, of which the most extensively characterized are the mu, delta and
      kappa receptors. We have now cloned the human homolog of the mu opioid receptor
      and, in the present study, we have examined its pharmacological profile. The
      human mu receptor has high affinities for several alkaloids of high abuse
      potential as well as a variety of peptide and nonpeptide drugs characterized
      previously as mu-selective, but not delta- or kappa-selective. Most importantly,
      the human mu receptor has higher affinity for morphine and methadone than does
      the rat mu receptor, despite the fact that these receptors are 95% identical at
      the amino acid level. The labeling of the receptor by agonist was decreased by
      nonhydrolyzable GTP analogs and by pertussis toxin treatment of cells expressing
      the human mu receptor, consistent with the coupling of the receptor to guanine
      nucleotide binding proteins. The human mu receptor functionally couples to the
      inhibition of adenylyl cyclase in a stereospecific and naloxone-reversible
      manner. We have also investigated the distribution of mRNAs encoding the mu
      receptor in human brain by Northern analysis, which demonstrates the existence of
      multiple transcripts of 13.5, 11, 4.3 and 2.8 kb, which were highly expressed in
      the hypothalamus, thalamus and subthalamic nucleus, more moderately expressed in
      the amygdala and caudate nucleus and which demonstrated lowest levels of
      expression in the hippocampus, substantia nigra and corpus callosum.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7815361
TI  - gamma-Aminobutyric acid gating of Cl- channels in recombinant GABAA receptors.
AB  - We studied gamma-aminobutyric acid (GABA) gated whole-cell Cl- currents after
      rapid transmitter application (< 10 ms) to cells expressing structurally
      different recombinant GABAA receptors. A variety of recombinant receptors were
      transiently transfected in a human cell line with three cDNAs encoding for
      different molecular forms of alpha-, beta- and gamma-subunits of the GABAA
      receptors. The maximal current amplitude elicited by GABA on recombinant GABAA
      receptors was greater when the alpha-subunits were combined with beta 2 gamma 2
      subunits than with beta 1 gamma 2-subunits, with the exception of receptors
      including the alpha 6-subunit. The maximal current amplitude elicited by GABA was
      greater when the beta-subunits were combined with gamma 2 alpha 1-subunits than
      with gamma 1 alpha 1 subunits, with the exception of receptors including the beta
      3-subunit. Furthermore, receptors comprising the beta 3-subunit had a greater
      sensitivity to GABA than those including the beta 1-or beta 2-subunits. When the
      gamma-subunits were substituted in receptors including alpha- and beta-subunits,
      the greatest current amplitude elicited by GABA was obtained with the alpha 1
      beta 2 gamma 2 combination, whereas the GABA potency was greater with alpha 1
      beta 2 gamma 1 and alpha 1 beta 1 gamma 3 than with the alpha 1 beta 2 gamma 2
      combination. In receptors including alpha 6 beta 2-subunits the rank order of
      GABA maximal current amplitude was gamma 1 > gamma 2 > delta subunits.

PMID- 7815362
TI  - Is the "atypical" beta-receptor in the rat stomach fundus the rat beta 3
      receptor?
AB  - The rat gastric fundus is known to possess an "atypical" beta-adrenergic receptor
      that mediates relaxation to isoproterenol. The purpose of this study was to
      characterize the relationship between this "atypical" beta receptor in the rat
      stomach and the cloned rat beta 3 receptor by taking advantage of highly
      selective pharmacological and molecular biological probes of the beta 3 receptor.
      Nuclease protection analysis of RNA from the rat gastric fundus identified beta 3
      receptor mRNA whose levels in the stomach were exceeded only by those in adipose
      tissue. Pharmacological analysis of the recombinant rat beta 3 receptor expressed
      in Chinese hamster ovary cells indicated low affinity of propranolol with a Ki
      value of 2.3 microM. Therefore, 0.3 microM propranolol was chosen as a
      concentration that would completely block beta 1 and beta 2 receptors (Ki = 1-5
      nM) but would leave beta 3 receptors largely intact in the rat stomach fundus. In
      the presence of propranolol, several beta-adrenergic receptor agonists relaxed
      the rat stomach fundus with a rank potency order of (R,R)-5-[2-[[2-(3
      chlorophenyl)-2-hydroxyethyl]-amino]-propyl]1,3- benzodioxole-2,2-dicarboxylate
      (CL316,243) > isoproterenol > norepinephrine = epinephrine = dl-4-3[(1,1
      dimethylethyl)amino]-2- hydroxylproproy]1,3 dihydro-2H-benzimidazol-2-one
      hydrochloride (CGP12177) > clenbuterol > terbutaline > pindolol. Isoproterenol,
      norepinephrine and epinephrine were full agonists, whereas (R,R)-5-[2-[[2-(3
      chlorophenyl)-2- hydroxyethyl]-amino]-propyl]1,3-benzodioxole-2,2-dicarboxylate
      was only a partial agonist with 66% intrinsic activity relative to
      isoproterenol.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7815363
TI  - Acetic acid-induced colitis in normal and essential fatty acid deficient rats.
AB  - Eicosanoids and platelet-activating factor (PAF) production increases in
      experimental colitis. Both eicosanoids and PAF seem to arise from similar
      membrane phospholipids. To support both these suggestions we have investigated
      whether a fat-free diet, which should alter production of eicosanoids and PAF,
      affects experimental colitis. Essential fatty acid deficient (EFAD) rats were
      obtained by putting 4-week-old animals on a fat-free diet for 3 months.
      Experimental colitis was induced by a single intracolonic administration of 2 ml
      of 4% acetic acid. One to seven days later the animals were sacrificed and the
      colon removed to assess macroscopically and histologically intestinal damage.
      Eicosanoids and PAF levels were also measured in the mucosa scrapings by specific
      radioimmunoassay. The injury to the colon was more evident in control rats
      compared with EFAD rats. Besides colonic tissue of control rats showed a highly
      significant increase of PGE2, LTB4 and PAF, compared with levels in EFAD rats.
      Our results indicate that fat-free diet reduces tissue damage, and at the same
      time PGE2, LTB4 and PAF colonic content.

PMID- 7815364
TI  - The coagulation system, but not circulating fibrinogen, contributes to liver
      injury in rats exposed to lipopolysaccharide from gram-negative bacteria.
AB  - Evidence suggests that components of the coagulation system contribute to the
      pathogenesis of liver injury after exposure to lipopolysaccharide (LPS) from gram
      negative bacteria. Although the mechanism by which the coagulation system
      mediates liver injury remains unknown, it has been proposed that the conversion
      of fibrinogen to insoluble fibrin and consequent deposition in liver
      microvasculature may contribute to the development of liver injury. The purpose
      of this study was to test the hypothesis that the coagulation system contributes
      to LPS hepatotoxicity by a mechanism which is dependent on circulating
      fibrinogen. A marked reduction in plasma fibrinogen concentration occurred in
      rats after LPS exposure. The decrease in circulating fibrinogen, which marked
      activation of the coagulation cascade: 1) occurred at doses of LPS that caused
      liver injury; 2) was temporally associated with the onset of liver injury; and 3)
      was attenuated by pretreatment with heparin or warfarin under conditions which
      afforded protection against liver injury. Pretreatment with either pentoxifylline
      or antiserum to tumor necrosis factor-alpha, both of which protect against LPS
      hepatotoxicity, also attenuated the LPS-induced decrease in circulating
      fibrinogen. Polymorphonuclear leukocyte (neutrophil) depletion protected against
      liver injury after administration of either a small (2 mg/kg) or a large (8
      mg/kg) dose of LPS and attenuated the decrease in circulating fibrinogen albeit
      to a lesser degree after the larger LPS dose. Depletion of circulating fibrinogen
      with ancrod did not afford protection against LPS hepatotoxicity. These results
      suggest that the coagulation system contributes to the pathogenesis of LPS
      induced liver injury, but it does so by a mechanism which is independent of
      circulating fibrinogen.

PMID- 7815365
TI  - Transport of oral cephalosporins by the H+/dipeptide cotransporter and
      distribution of the transport activity in isolated rabbit intestinal epithelial
      cells.
AB  - Transport of cephalosporins was studied using isolated rabbit intestinal
      epithelial cells. Cephradine uptake by the cells was concentrative and was
      inhibited by the addition of glycylsarcosine. The accumulated cephradine was
      effluxed from the cells by the addition of a protonophore, carbonyl cyanide 4
      trifluoromethoxyphenylhydrazone (FCCP). Amiloride, an inhibitor of the Na+/H+
      exchanger, reduced the steady-state uptake of cephradine, suggesting that the
      exchanger contributes to the maintenance of an inward H+ gradient as a driving
      force. Cephradine uptake by ATP-depleted intestinal cells was actively driven by
      the inward H+ gradient and was inhibited by FCCP and glycylsarcosine. The
      distribution of cephradine transport activity along the small intestine and
      villus-crypt axis was also examined in the isolated cells, and the transport
      activity was higher in the upper parts of the intestinal segments and in villus
      cells. These results indicate that the uptake of oral cephalosporins by
      intestinal epithelial cells in concentrative and reversible and that the
      H+/dipeptide cotransporter and the Na+/H+ exchanger play an important role for
      the active uptake of these drugs. The activity of the H+/dipeptide cotransporter
      should be higher in upper segments and in villus cells of the small intestine.

PMID- 7815366
TI  - Activation of endogenous thromboxane A2 biosynthesis mediates presynaptic
      inhibition by endothelin-3 of dog stellate ganglionic transmission.
AB  - Effects of endothelin-3 on ganglionic transmission were investigated in dog
      cardiac sympathetic ganglia. Positive chronotropic responses to preganglionic
      stellate stimulation were inhibited by endothelin-3 (0.5-2 micrograms) given
      directly to the ganglia through the artery. To find possible inhibitory effects
      of the peptide at presynaptic sites, acetylcholine released from the isolated
      stellate ganglia was determined. The amount of acetylcholine released during
      preganglionic stimulation was reduced by exposure to endothelin-3 (10(-9) to 10(
      6) M). A similar reduction of acetylcholine release was observed after
      application of a stable thromboxane A2, a thromboxane A2/prostaglandin H2
      receptor agonist, U-46619, and prostaglandin E2 at concentrations from 10(-8) to
      10(-4) M, but not by the same concentrations of prostaglandins F2 alpha and I2.
      The reduction elicited by endothelin-3 was unaffected by a phospholipase C
      inhibitor, neomycin, or a protein kinase C inhibitor, H-7, but was antagonized by
      pretreatment with phospholipase A2 inhibitors, dexamethasone or
      methylprednisolone, and by cyclooxygenase inhibitors, aspirin and indomethacin.
      In addition, the reduction also was antagonized by pretreatment with a
      thromboxane A2 synthetase inhibitor, OKY-046, and a specific thromboxane A2
      receptor antagonist, S-145, but not by a specific prostaglandin E2 receptor
      antagonist, SC-19220. Furthermore, endothelin-3 (10(-7) M) stimulated the OKY-046
      and indomethacin-sensitive formation of thromboxane A2 in the ganglia. These
      results indicate that endothelin-3 inhibits the sympathetic ganglionic
      transmission by reducing acetylcholine release at preganglionic terminals and
      that this inhibition seems to involve activation of endogenous thromboxane A2
      production.

PMID- 7815367
TI  - Neurotransmitter-specific profiles of inositol phosphates in rat brain cortex:
      relation to the mode of receptor activation of phosphoinositide phospholipase C.
AB  - Phosphoinositide breakdown, as stimulated by six different neurotransmitter
      receptor agonists (carbachol, serotonin, norepinephrine, trans-(+/-)
      aminocyclopentyl-1,3-dicarboxylic acid, endothelin-1 and histamine), has been
      studied in rat brain cortical slices. The accumulation was monitored of total 3H
      inositol phosphates (InsPs) and [3H]CDP-diacylglycerol (CDP-DAG) in [3H]inositol
      or [3H]cytidine-prelabeled tissue, respectively, and the profile of the major
      InsPs was quantified as the index log [(inositol 4-monophosphate + inositol 1,4
      bisphosphate)/inositol 1-monophosphate]. The efficacy of the six agonists to
      stimulate the accumulation of CDP-DAG, relative to that of InsPs, was not
      constant, which revealed varying degrees of defective recycling of DAG to CDP
      DAG. The value of the index for the profile of InsPs was not constant either but
      was characteristic of each agonist. Both parameters (ratio of efficacies CDP
      DAG/InsPs and InsPs profile) were not independent and defined two groups of
      agonists as follows: group a, carbachol and serotonin, with balanced CDP-DAG and
      InsPs responses, and Ins1P prevailing against inositol 4-monophosphate + inositol
      1,4-bisphosphate and group b, norepinephrine, trans-(+/-)-aminocyclopentyl-1,3
      dicarboxylic acid, endothelin-1 and histamine, with weak CDP-DAG responses and
      high accumulation of inositol 4-monophosphate + inositol 1,4-bisphosphate
      compared with that of inositol 1-monophosphate. In a membrane preparation from
      brain cortex, only agonists in group a stimulated phospholipase C in the presence
      of guanosine 5'-O-(3-thiotriphosphate) and in a receptor antagonist-sensitive
      fashion, which indicated that brain cortical alpha-1, H1, endothelin and
      glutamate metabotropic receptors stimulate phospholipase C indirectly.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7815368
TI  - Subtype-specific changes in ligand binding properties after solubilization of
      muscarinic receptors from baculovirus-infected Sf9 insect cell membranes.
AB  - Ligand binding properties of membrane-bound and solubilized muscarinic
      acetylcholine receptor (mAChR) subtypes (human m1 and m2; rat m3 and m4),
      produced by using a baculovirus infection system in Sf9 insect cells have been
      studied. Most of the studied ligands that have been proposed previously to be
      selective for some subtype had similar selectivity to mAChRs in Sf9 cell
      membranes. Only tropicamide, which has been proposed as m4-specific ligand, had
      higher affinity for m1. Solubilization of receptors decreased binding affinities
      of all studied ligands to m1 and m3 mAChR, on average 10- and 75-fold,
      respectively. The solubilization of m2 mAChR had only slight influence on the
      affinity of subtype nonspecific ligands, but decreased 5- to 10-fold the
      affinities of m2-specific ligands and increased up to 6-fold the affinities of m1
      and m3-specific ligands. Effects of m4 mAChR were similar to those on m2, but
      without a decrease in affinities of m2-specific ligands. This combination of
      reduction and increase of binding affinities caused by solubilization led to loss
      of subtype selectivity of most ligands studied. Only AF-DX 116 [11-((2
      [(diethylamino)-methyl]-1- piperidinyl)-acetyl)-5,11-dihydro-6H-pyrido(2,3b)
      (1,4)-benzodiazepin -6-ontelenzepine] and gallamine retained their selectivity
      for m2 after solubilization of mAChR. Incorporation of mAChR into brain membranes
      restored their subtype specificity in ligand binding. These data suggest that
      subtype-specific antagonist binding to mAChR is generally modulated by the lipid
      environment of receptor protein.

PMID- 7815369
TI  - Specific effects of zatebradine on sinus node function: suppression of
      automaticity, prolongation of sinoatrial conduction and pacemaker shift in the
      denervated canine heart.
AB  - We evaluated the cardiac electrophysiological effects of zatebradine in eight
      anesthetized and autonomically denervated canines, with particular emphasis on
      the effects on sinus node automaticity and sinoatrial conduction (SACT), both at
      rest and after atrial overdrive pacing. Sinus node function was assessed by using
      the recorded sinus node electrogram and also by applying a previously validated
      mathematical model of sinus node function which allows separate evaluation of
      effects of pacing on SACT and suppression of automaticity. Other standard
      electrophysiological parameters also were measured. Tests were performed before
      and after incremental doses of zatebradine (0.0625, 0.125 and 0.25 mg/kg).
      Zatebradine caused a significant, dose-related increase in cardiac cycle length.
      There also was a significant, dose-related increase in both suppression of
      automaticity and SACT (independent of changes in cycle length) after zatebradine.
      The only other significant electrophysiological effect was a relatively minor
      increase in the ventricular effective refractory period (13%). Higher doses of
      zatebradine were associated with spontaneous pacemaker shift characterized by
      loss of the sinus node electrogram and variation in P-wave morphology. Our
      results confirm that the effects of zatebradine are relatively specific for the
      sinus node. These included: 1) prolongation of resting sinus cycle length; 2)
      enhanced suppression of automaticity after overdrive pacing; 3) prolongation of
      SACT; and 4) induction of sinus node pacemaker shifts. This agent should be used
      cautiously in patients with possible sinus node dysfunction.

PMID- 7815370
TI  - Effects of probenecid and cimetidine on the renal excretion of 3'-azido-3'
      deoxythymidine in rats.
AB  - The mechanisms underlying the inhibitory effects exerted by probenecid and
      cimetidine on the renal excretion of 3'-azido-3'-deoxythymidine (AZT) were
      investigated in rats in vivo. On i.v. administration, the findings indicated that
      both probenecid and cimetidine increased the plasma concentration of AZT and
      inhibited its renal excretion. To clarify the mechanisms underlying the
      interaction of these drugs with AZT and to elucidate the process of renal
      secretion of AZT, further investigation was performed, in which [3H]AZT (0.5
      microM) was injected rapidly into the right renal artery, and its outflow profile
      from the right ureter was compared with that from the left ureter. In control
      experiments, 56.6% of the administered AZT was secreted from the right kidney,
      and it was calculated that the transcellular transit time of AZT in this process
      was 0.30 min. In the presence of 10 mM probenecid and of 10 mM cimetidine, the
      secretion of AZT was reduced to 15.3 and 32.3%, respectively, the inhibition
      induced by probenecid being more effective than that induced by cimetidine.
      However, the transcellular transit time of AZT increased to 0.53 and 1.21 min in
      the probenecid and cimetidine studies, respectively. Thus, cimetidine was more
      potent than probenecid in its effects on the transit time. These findings
      indicate that probenecid and cimetidine affect different steps in the renal
      secretion of AZT. It was therefore concluded that, on the renal plasma membrane,
      AZT is transported by anion transport systems, whereas on the brush border
      membrane, AZT is secreted by cation transport systems.

PMID- 7815371
TI  - Metastatic tumors to the jawbones: analysis of 390 cases.
AB  - A review of the English language literature revealed 390 well-documented cases of
      metastatic lesions to the jawbones. Most metastatic lesions were diagnosed in
      patients in their fifth to seventh decade. The primary site differed between the
      genders: for women, it was the breast followed by the adrenal, colo-rectum,
      female genital organs and thyroid; for men, it was the lung, followed by the
      prostate, kidney, bone and adrenal. The most common location of the metastatic
      tumors was the mandible, with the molar area the most frequent site involved. In
      about 30% of cases the oral lesion was the first sign of the malignant disease.
      The present data are compared with those of metastatic tumors to the oral mucosa
      and a view on the possible pathogenesis is presented.

PMID- 7815372
TI  - Immunohistochemical detection of the H-ras, K-ras, and N-ras oncogenes in
      squamous cell carcinoma of the head and neck.
AB  - The expression of H-ras, K-ras and N-ras oncogenes was analyzed on frozen
      sections of squamous cell carcinoma of the head and neck (SCCHN) by
      immunohistochemistry using anti-ras monoclonal antibodies. Of 22 primary SCCHN,
      15 (68%) stained positive for H-ras, 10 (45%) for K-ras and seven (32%) for N
      ras. Thirteen specimens (59%) stained positive for at least two anti-ras
      monoclonal antibodies. The presence of immunohistochemically detectable H-ras, K
      ras and N-ras proteins was most frequently associated with an increase in tumor
      size and later stages of disease (T3 and T4), with no apparent correlation with
      lymph node involvement, site of occurrence, degree of differentiation, age, sex,
      or race. Thus, overexpression of members of the ras gene family occurs as a
      relatively common even in SCCHN and may be an important event in the later stages
      of tumorigenesis.

PMID- 7815373
TI  - IL-4- and IL-6-producing cells in human periodontal disease tissue.
AB  - IL-4- and IL-6-producing cells in human periodontal disease tissues were
      investigated using immunohistochemical and in situ hybridization techniques.
      Immunohistochemical analysis demonstrated the presence of IL-4-producing cells
      within the CD45RO+ subset and the percentage of IL-4+ cells was significantly
      higher in periodontal lesions than in gingivitis tissues (p < 0.01). The
      percentage of IL-6-producing memory cells was higher in periodontal lesions
      compared with gingivitis tissues, although it was not statistically significant
      (p > 0.05). A reverse tendency in IL-4- and IL-6-positive cells was observed in a
      few individual cases. No IL-4 mRNA could be detected using the in situ
      hybridization technique. However, high levels of IL-6 mRNA were present in
      clinically healthy tissues, with a further increase in both epithelium and
      connective tissues affected by gingivitis, although only the former was
      significant (p < 0.025). There was a significant decrease in IL-6 mRNA in both
      the connective tissue (p < 0.025) and epithelium (p < 0.01) in periodontitis
      tissues compared with levels in gingivitis tissues. However, the levels of IL-6
      mRNA in periodontal tissues were high compared with those of IL-1 mRNA, which was
      used in this study as a positive control. These results suggest that Th2-type
      cells may accumulate in periodontal lesions.

PMID- 7815374
TI  - Association of amyloid P protein with pathology in periodontal tissues.
AB  - The lesion of chronic periodontitis is characterized by the persistence of
      perivascular collections of degenerate plasma cells. In this study,
      immunohistochemical demonstration of amyloid P (AP) component was used to define
      the distribution of this protein in established periodontitis lesions and in
      biopsies of non-destructive marginal gingivitis. Quantitative assessment of AP
      indicated significantly higher levels in periodontitis than in gingivitis for all
      regions of the tissue. This was associated with pathology as determined by the
      intensity of plasma cell accumulation and the extent of connective tissue matrix
      degradation. AP was concentrated in the deep connective tissue areas but
      perivascular accumulation was also noted, as was deposition associated with nerve
      bundles and, occasionally, in the extracellular matrix of the lining epithelium.
      These findings have potential significance in relation to the pathology of
      chronic periodontitis as AP has been shown to interact in a calcium-dependent
      manner with a number of ligands including fibronectin, elastic fibres, C-4
      binding protein and amyloid fibrils.

PMID- 7815375
TI  - Extraction of amyloid-like fibrils from chronically inflamed periodontal tissues.
AB  - Immunohistological studies have established an association between the deposition
      of the amyloid P protein and disease status in chronically inflamed periodontal
      tissues. The aim of this study was to determine if amyloid-like fibrils could be
      extracted from these tissues. Biopsies were homogenised and extracted
      exhaustively in saline before serial extraction in distilled water.
      Electrophoretic analysis revealed the presence of previously undetected protein
      bands in the fifth water extraction. These were probed and were found to react
      with antisera to kappa and lambda immunoglobulin light chains but not with
      antisera to mu, gamma or alpha heavy chains. Electron microscopic study indicated
      fibrils of 9.7 nm diameter. These bound Congo Red and exhibited green
      birefringence under polarised light. The results supported the presence of an
      amyloid-like matrix composed of immunoglobulin light chains in the lesions of
      chronic periodontitis. This could explain the persistence of foci of degenerate
      plasma cells and the paucity of granulation tissue formation in the disease
      process.

PMID- 7815376
TI  - The person behind the eponym: Sir James Paget (1814-1899).

PMID- 7815377
TI  - Notes on emotional components of musical creativity and performance.
AB  - We explored emotional accompaniments to stages of a musician's cycle of
      creativity through interviews with musicians. Creativity was defined in terms of
      performance or composition. These musicians described strong emotional
      vacillations that occur across the creative cycle and discussed ways of dealing
      with emotional issues involved in moving from one work to the next. Parallels
      were drawn between emotional aspects of completing a performance or composition
      to emotional aspects of termination in psychotherapy. Suggestions were offered to
      musicians for means of dealing with naturally occurring but powerful emotional
      components of creativity. In addition, some of the musicians suggested that music
      educators consider teaching students about potential emotional issues that may
      accompany creative effort. An integration of these issues into music education
      programs might better prepare students for careers as professional musicians.

PMID- 7815378
TI  - A comparison of cognitive and behavioral inductions of negative mood.
AB  - Sixty undergraduate subjects were exposed to one of three depressive mood
      inductions: cognitive, behavioral, or control. Subjects in the cognitive
      induction group read negative self-statements consistent with Beck's (1974)
      cognitive theory of depression. Subjects in the behavioral induction group were
      exposed to insoluble discrimination problems consistent with Lewinsohn's (1974)
      behavioral theory that lack of reinforcement produces depression. The control
      group read a neutral passage. Following the mood induction, subjects rated their
      current moods using the Multiple Affect Adjective Checklist (MAACL; Zuckerman &
      Lubin, 1965). The cognitive and behavioral inductions produced significantly
      higher MAACL total and subscale scores than did the control condition; however,
      the cognitive and behavioral inductions did not differ from one another. Because
      the cognitive and behavioral mood inductions appear equally powerful, they may be
      used by researchers who are attempting to identify variables that are related to
      subjects' differing responses to behavioral and cognitive influences on
      depression.

PMID- 7815379
TI  - Are age and ethics related?
AB  - Ethical values of 171 college students at California State University, Chico,
      were measured, using a subset of the Rokeach (1968, 1971) Value Survey.
      Nonparametric statistical analysis, four value measures, and four different
      consistent tests of significance and probability showed, surprisingly, that the
      younger students were more ethical than the older students. College students
      under 21 scored significantly higher ethically on three out of the four measures.
      Younger college students valued equality, freedom, and honesty more than their
      older classmates did. Surprisingly also, the younger students were significantly
      more concerned with being helpful and intellectual and were less involved in
      pursuing an exciting life and in social recognition than were the older students.

PMID- 7815381
TI  - Relationships between aspects of work-related psychological well-being.

PMID- 7815380
TI  - Interpersonal dependency correlates and locus of control orientation among obese
      adults in outpatient treatment for obesity.
AB  - Interpersonal dependency and locus of control orientation were studied in obese
      and nonobese samples. The Interpersonal Dependency Inventory (Hirschfeld,
      Klerman, Gough, Barrett, & Korchin, 1977) and the I-E Scale (Rotter, 1966) were
      administered to 106 obese adults in outpatient treatment for obesity. The I-E
      Scale was also administered to 97 nonobese control subjects. As predicted, the
      obese subjects were significantly more internally oriented than has been
      previously identified in obese populations. These findings challenge currently
      held assumptions about locus of control in obese groups. Although the obese and
      nonobese subjects maintained similar overall dependency scores, the obese
      subjects were more likely to show low levels of autonomy in comparison with the
      nonobese subjects. Interpersonal dependency and locus of control dimensions
      associated with obese conditions may serve as useful predictor variables
      influencing obesity treatment approaches and outcome.

PMID- 7815382
TI  - Gender differences in prediction of grade performance from graduate record
      examination scores.

PMID- 7815383
TI  - Obsessive actions and religious practices.

PMID- 7815384
TI  - Onset and terminal sensations in out-of-body experiences.

PMID- 7815385
TI  - The Emory Dyssemia Index: a brief screening instrument for the identification of
      nonverbal language deficits in elementary school children.

PMID- 7815386
TI  - Independent and coordinate regulation of beta 1- and beta 2-adrenergic receptors
      in rat C6 glioma cells.
AB  - Rat C6 glioma cells have both beta 1- and beta 2-adrenergic receptors in
      approximately 7:3 ratio. When the cells were exposed to the beta-adrenergic
      agonist isoproterenol, there was a rapid sequestration of up to 50% of the
      surface receptor population over a 30-min period as measured by the loss of
      binding of the hydrophilic ligand [3H] CGP-12177 to intact cells. Using the beta
      1-selective antagonist CGP 20712A to quantify the proportion of the two subtypes,
      it was found that although both beta 1 and beta 2 receptors were sequestered, the
      latter were sequestered initially twice as fast as the former. More prolonged
      agonist exposure led to a down-regulation of approximately 90% of the total
      receptor population by 6 h as measured by the loss of binding of the more
      hydrophobic ligand [125I]iodocyanopindolol to cell lysates. The two subtypes,
      however, underwent down-regulation with similar kinetics. Treatment of the cells
      with agents that raise cyclic AMP levels such as cholera toxin and forskolin
      resulted in a slower, but still coordinated down-regulation of both subtypes.
      Thus, there appears to be both independent and coordinate regulation of
      endogenous beta 1-and beta 2-adrenergic receptors in the same cell line.

PMID- 7815387
TI  - Dexamethasone mediated stabilization of insulin receptor mRNA.
AB  - To determine the mechanism of glucocorticoid mediated enhancement of insulin
      receptor (IR) gene expression, we cotransfected a glucocorticoid receptor
      expression vector and a plasmid containing a reporter gene driven by an MMTV or
      IR promoter into COS 7 cells. Dexamethasone (Dex) increased MMTV promoter
      activity by 100% but had no effect on IR promoter activity. In the glucocorticoid
      responsive breast cancer cell line, MCF-7, Dex increased IR mRNA by 60%, and
      increased the IR mRNA half-life from approximately 6hrs to > 24 hrs. No
      glucocorticoid responsive element could be located in the insulin receptor 3'
      untranslated region. Glucocorticoids stabilize IR mRNA.

PMID- 7815388
TI  - Neurotensin binding to human embryonic lung fibroblasts.
AB  - Several neuropeptides have been shown to regulate the function of cells involved
      in immune response and inflammation. Neurotensin is a 13 amino acid neuropeptide
      localized primarily to the nervous system and gut. Neurotensin also stimulates
      mast cell degranulation and enhances phagocytic and cytolytic capability of
      macrophages, suggesting that this peptide regulates inflammatory and immune
      responses. Fibroblasts play an important role in inflammation and tissue healing,
      and these processes may be regulated by several neuropeptides that have been
      shown to bind to fibroblasts. However neurotensin receptors have not been
      identified on fibroblasts. Human embryonic lung fibroblasts (HELF) were examined
      for binding and biological effects of neurotensin. 125I-neurotensin binding to
      adherent and confluent human embryonic lung fibroblasts (HELF), plated in 12mm
      diameter wells was specific and saturable. Computer-assisted resolution of the
      binding data demonstrated two classes of binding sites: a high affinity, low
      capacity site (Kd = 1.6 x 10(-11) M, 19.5 x 10(7) sites/well), and a low-
      affinity, high-capacity site (Kd = 10(-8) M, 4 x 10(9) sites/well). Neurotensin
      stimulated immediate, transient, dose-dependent increases of cytosolic calcium in
      HELF (threshold dose: 10(-11) M), suggesting release of calcium from
      intracellular stores. The novel finding of neurotensin receptors on fibroblasts
      provides further support for this neuropeptide's role as a regulator of
      inflammatory and immune responses.

PMID- 7815389
TI  - Surface distribution of the EGF receptor during differentiation of the human
      colon carcinoma cell line HT29-D4.
AB  - The clone HT29-D4 can be induced to differentiate into enterocyte-like cells, by
      simply removing glucose from culture medium. In this report, we used the HT29-D4
      model to study the membrane segregation of the EGF receptor on epithelial
      intestinal cells. Differentiated and undifferentiated cells displayed a single
      class of EGF binding sites with similar dissociation constants. However,
      differentiation of HT29-D4 led to a 3-fold decrease in the total number of EGF
      binding sites, while the number of IGF-I binding sites was unchanged. Fifteen
      percent of EGF receptors present on differentiated HT29-D4 cells were localized
      in the apical surface, whereas 98% of IGF-I receptors were segregated to the
      basolateral domain. By covalent cross-linking experiments using 125I-EGF and by
      immunoprecipitation with an anti-EGF receptor antibody, we have characterized the
      HT29-D4 EGF receptor as a Mr = 165,000 protein in both differentiated and
      undifferentiated cells. Apical EGF receptors were functional, as evidenced by
      their ability to be internalized in response to EGF binding. Thus, intact and
      functional EGF receptors are present at the apical surface of differentiated HT29
      D4 cells, suggesting the presence of EGF receptors on the apical domain of
      enterocytes.

PMID- 7815390
TI  - Odor-induced host location in tsetse flies (Diptera: Glossinidae)
AB  - Four aspects of olfaction in host location by tsetse flies, Glossina spp., are
      discussed as follows: (1) host location and its mechanism, (2) factors affecting
      host location, (3) kairomones and host location, and (4) kairomones and host
      selection. Flight behavior in the various phases of host location (i.e., ranging,
      activation, orientation, and landing) in the absence and presence of olfactory
      cues is summarized. Movement toward an odor source is effected inter alia through
      optomotor-steered, upwind anemotaxis. It is still unclear how tsetse employ
      upwind anemotaxis to realize host location, considering the often highly variable
      wind direction. Olfactorily induced activation is governed by the olfactory cue
      perceived and threshold levels set by the internal state of the fly. The former
      depends on the odor source and distance from it; the latter is determined by
      species, sex, and physiological state. Wind direction and speed, as well as
      vegetation and the mobility of the host, interfere with successful completion of
      odor-induced host location. Close-range olfactory cues (including composition and
      concentration gradients), visual cues, and nutritional state determine whether a
      fly, having reached the host animal, will land on it. Carbon dioxide is important
      in host location because it induces landing and long-range attraction. The role
      of the other kairomones (acetone, 1-octen-3-ol, 4-methyl-phenol, and 3-n-propyl
      phenol) is less clear. Apart from the complacency of various host species under
      tsetse attack, host choice by tsetse is predominantly opportunistic and primarily
      the result of the frequency of successful tsetse-host encounters. Nevertheless,
      host selection based on olfactory cues cannot be ruled out.

PMID- 7815391
TI  - Siphonaptera of North America north of Mexico: Hystrichopsyllidae s. str.
AB  - The three species of Atyphloceras Jordan & Rothschild, 1915 and the four species
      of Hystrichopsylla Taschenberg, 1880 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 diagnostic characters are illustrated.

PMID- 7815392
TI  - Ultrastructure of the eggs of seven flea species (Siphonaptera).
AB  - Eggs of seven flea species representing five families, Ctenocephalides felis
      (Bouche) (Pulicidae), Orchopeas leucopus (Baker) and Aetheca wagneri (Baker)
      (Ceratophyllidae), Conorhinopsylla stanfordi Stewart and Epitedia faceta
      (Rothschild) (Hystrichopsyllidae), Sternopsylla distincta texana (C. Fox)
      (Ischnopsyllidae), and Craneopsylla minerva (Rothschild) (Stephanocircidae), were
      examined with a scanning electron microscope and are described from the resulting
      micrographs. In the Pulicidae and Ceratophyllidae the individual outer chorionic
      cells are not visible; the egg surfaces are covered uniformly with small, nodular
      tubercles. In contrast, the Hystrichopsyllidae and Ischnopsyllidae have a
      prominent, raised reticulum, very heavily constructed in the latter, delineating
      the chorionic cells. The single representative of the Stephanocircidae has only a
      faintly embossed chorionic reticulum. All of the species examined except E.
      faceta and C. minerva (both with a single micropylar opening) have multiple
      micropyles at the posterior end. C. felis, O. leucopus, A. wagneri, and C.
      stanfordi also have multiple aeropyles at the anterior end (these are lacking in
      S. d. texana). Lateral aeropyles, consisting of small groups of pores often
      associated with small mounds in the chorion, are present (maximum of two seen on
      any one egg) in all species except E. faceta, C. stanfordi, and C. minerva.

PMID- 7815393
TI  - Traps and baits for flies (Diptera) on Pacific Islands.
AB  - Studies conducted on Oahu, HI, and on islands of the Kwajalein Atoll, Marshall
      Islands, demonstrated that adult house flies, Musca domestica L., were attracted
      to a mixture of cooked rice and chicken and to a commercial bait, whereas adults
      of Chrysomya megacephala F. and Musca sorbens Wiedemann were attracted to shark
      fluids or to ripe breadfruit. M. domestica and M. sorbens could be captured in
      standard inverted-cone traps, whereas C. megacephala could be captured in traps
      fitted with horizontal entry cones or in cone traps in which the bait was placed
      inside the cone chamber. M. sorbens and C. megacephala were killed by horizontal
      electric grids placed over yellow plastic or paper at ground level. M. sorbens
      was attracted to 15-cm cubes, but not to larger objects.

PMID- 7815395
TI  - Fecundity and proportions of gravid females in populations of the bluetongue
      vector Culicoides imicola (Diptera: Ceratopogonidae) and several other species in
      Israel.
AB  - The gravid proportions of five Culicoides spp. in Israel were determined based on
      a suction light trap placed above calves in a cowshed and on two similar traps
      hung in a Eucalyptus tree at elevations of 1.4 and 26 m. In the cowshed, the
      proportion of gravid Culicoides distinctipennis Austen showed no significant
      variation between seasons; C. imicola Kieffer (the dominant species) was caught
      in significantly smaller proportions in winter; C. schultzei gp (second most
      dominant) showed no significant seasonal variation. In the Eucalyptus tree, a
      significantly smaller percentage was gravid in winter at the lower trap, but at
      the higher trap there was no significant variation between seasons. Culicoides
      circumscriptus Kieffer showed no significant seasonal variation at either height.
      C. distinctipennis was present with a significantly higher proportion gravid at
      the lower level in spring, but no significant variation between seasons was
      observed in the higher level trap. In C. imicola, gravids were proportionately
      more numerous in the lower trap in summer and autumn, but, in the higher trap,
      there was no significant variation between seasons. A significantly greater
      proportion of gravid C. schultzei gp females occurred at the higher level trap in
      spring, whereas no significant variation occurred in the lower level trap. Counts
      of eggs were made for C. cataneii, C. circumscriptus, C. distinctipennis, C.
      imicola, C. newsteadi Austen, C. obsoletus Meigen, C. saevanicus Dzhafarov, C.
      schultzei gp, and C. univittatus Vimmer. Counts for all four seasons were made
      only for C. circumscriptus and C. imicola, and only C. imicola showed significant
      variation between seasons (fecundity lower in autmn and winter).

PMID- 7815394
TI  - Toxicity of extracts from three Tagetes against adults and larvae of yellow fever
      mosquito and Anopheles stephensi (Diptera: Culicidae).
AB  - Whole-plant Soxhlet extractions for the three Tagetes species showed that T.
      minuta had the greatest biocidal effect on the larvae and adults of Aedes aegypti
      (L.) and Anopheles stephensi Liston. Bioassays of simultaneous steam distillation
      extractions of the various parts of T. minuta found extracts from the flowers
      provided LD90s of 4 and 8 ppm against the larvae and 0.4 and 0.45% against the
      adults of A. aegypti and A. stephensi, respectively. Further research on T.
      minuta floral extracts as new biorational insecticides are discussed.

PMID- 7815397
TI  - Population dynamics of Lutzomyia shannoni (Diptera: Psychodidae) in relation to
      the epizootiology of vesicular stomatitis virus on Ossabaw Island, Georgia.
AB  - Population dynamics of Lutzomyia shannoni Dyar were studied on Ossabaw Island,
      GA, to define further the role of this species in the epizootiology of the New
      Jersey serotype of vesicular stomatitis (VSNJ) virus. Bimonthly collections of
      sand flies egressing from hollow trees from April to November 1991 indicated that
      there were three generations of sand flies. Data from light trap collections from
      1986 through 1989 indicated that similar seasonal cycles occurred during previous
      years. At this site, we hypothesize that L. shannoni undergoes facultative
      diapause. Two isolates of VSNJ virus were obtained from female sand flies
      collected in May and June of 1991. We believe that the virus overwinters in
      immature L. shannoni and that transovarially infected sand flies emerging each
      spring initiate a summer amplification cycle in swine on Ossabaw Island.

PMID- 7815396
TI  - Trombiculid fauna and seasonal abundance of Leptotrombidium scutellare (Acari:
      Trombiculidae) in an endemic area of scrub typhus (Tsutsugamushi disease) in
      Yamakita Town, Kanagawa Prefecture, Japan.
AB  - Using the Tullgren funnel method, we surveyed for trombiculid larvae around
      dwellings and in mandarin orange groves on the slopes of Sengenyama and Maruyama,
      Yamakita Town, Kanagawa Prefecture, Japan, during the period between 8 October
      1992 and 8 January 1993. In total, 6,690 trombiculid larvae, consisting of 6,669
      Leptotrombidium scutellare (Nagayo, Mitamura, Tamiya & Tenjin), 13 L. fuji
      Kuwata, Berge & Philip, two L. himizu (Sasa, Kumada, Hayashi, Enomoto, Fukuzumi &
      Obata), two Neotrombicula japonica (Tanaka, Kaiwa, Teramura & Kagaya), one
      Gahrliepia saduski Womersley, and three Walchia ogatai Sasa & Teramura, were
      taken from 240 soil samples (40 samples, six times at intervals of 2-4 wk). From
      the above species composition, L. scutellare is suspected to be the sole vector
      of scrub typhus in the survey area, where the disease is known to be caused by
      two serotypic strains of Rickettsia tsutsugamushi Ogata, Kawasaki and Kuroki. L.
      scutellare larvae rapidly increased in number in late October to form an
      acuminate peak of abundance in early November, followed by a gradual wane.

PMID- 7815398
TI  - Morphology of long- and short-day eggs of Aedes atropalpus and A. epactius
      (Diptera: Culicidae).
AB  - Scanning electron micrographs are used to document differences in the shape and
      fine structure of long-day (16:8 [L:D] h) and short-day (8:16 [L:D] h) eggs of
      Aedes atropalpus (Coquillett) and Aedes epactius Dyar & Knab from Illinois. Both
      shape and structural detail differed much more in A. atropalpus than in A.
      epactius. Long-day eggs of A. atropalpus were significantly longer and narrower;
      their outer chorionic cells on both the ventral (upper) and lateral surfaces were
      significantly smaller in area, with fewer small tubercles, and the detailed
      structure, shown in a comprehensive series of micrographs, was distinctly
      different than those of the short-day eggs. Dimensional differences of the whole
      egg were much less apparent in A. epactius; only width was significantly greater
      in short-day eggs. However, the ventral and lateral chorionic cells in the 2-d
      length groups showed the same highly significant differences in area and numbers
      of small tubercles as in A. atropalpus. Fine structural differences also were
      much less apparent in the eggs of A. epactius.

PMID- 7815399
TI  - Blood meal manipulation and in vitro colony maintenance of Haematobia irritans
      (Diptera: Muscidae).
AB  - A series of experiments was conducted to determine survival and reproductive
      potential of Haematobia irritans (L.) adults that were fed sodium citrated-bovine
      blood diluted with deionized water, 0.5 M glucose, or 0.15 M sodium chloride
      (NaCl), or supplemented with adenosine triphosphate (ATP). Reproductive
      potential, measured by total number of larvae produced per female during 10-d
      experimental periods, improved when adult H. irritans were fed blood diluted by <
      22% with deionized water, NaCl, or glucose, whereas female survival improved when
      fed blood diluted with deionized water or NaCl (by approximately 25%). Male
      survival declined whenever blood meals were diluted. Larval production also
      improved when blood previously stored at -20 degrees C was diluted by
      approximately 21% with deionized water. Addition of ATP to blood stored at 3
      degrees C did not improve larval production or female survival; however, ATP
      added to blood stored at -20 degrees C increased larval production and female
      survival. Male survival was not improved by addition of ATP to previously
      refrigerated or frozen blood. Blood meals were toxic to H. irritans when > or = 5
      x 10(-2) M ATP was added to previously refrigerated or frozen blood. A colony of
      H. irritans was maintained for five generations by feeding adult flies on
      citrated bovine blood that had been stored at -20 degrees C, supplemented with 5
      x 10(-3) M ATP, and diluted with deionized water. Flies were fed through a nylon
      reinforced silicone membrane throughout this experimental period. Female survival
      and larval production were unaffected by the adult fly feeding regimen. Male
      survival was reduced during the F1, F2, and F3 generations; however, declines did
      not affect colony maintenance. Percentage pupation increased during the F2 and F3
      generations and adult eclosion declined in the F3 and F4 generations, changes
      attributed to conditions of larvae rearing. Potential for colony population
      growth was estimated using F4 female survival and resulting larval production,
      pupation, and adult eclosion. An approximate of 24-fold increase in population
      size per generation could be realized by collecting all eggs produced by 6-12-d
      old females.

PMID- 7815400
TI  - Landscape patterns of abundance of Ixodes scapularis (Acari: Ixodidae) on Shelter
      Island, New York.
AB  - Nymphal Ixodes scapularis Say, the vector of Lyme borreliosis, was most common in
      forested areas across Shelter Island, Suffolk County, New York, and least common
      in xeric habitats such as beach and grassland. At the scale of individual house
      yards, nymphs were most common at wooded edges of property and least common on
      lawns. The abundance of ticks at yard edges was positively correlated with
      numbers on lawns and in landscaping, suggesting that tick abundance in woods
      affects abundances in adjacent yards. Because 57% of all yard area is adjacent to
      woodlands on Shelter Island, public health efforts to reduce tick populations in
      wooded areas should supplement efforts by individual yard owners to decrease
      risk. Methods of tick control for woodlands should also be evaluated for their
      effect on tick populations in adjacent yard habitats.

PMID- 7815401
TI  - Transmission of Borrelia burgdorferi s.l. from mammal reservoirs to the primary
      vector of Lyme borreliosis, Ixodes ricinus (Acari: Ixodidae), in Sweden.
AB  - Factors regulating prevalence of Borrelia burgdorferi s.l. Johnson, Schmid, Hyde,
      Steigerwalt & Brenner in Ixodes ricinus (L.) were examined during 1991-1992 at
      Bogesund, near Stockholm in south-central Sweden. Nine species of small and
      medium-sized mammals (Sorex araneus L., S. minutus L., Neomys fodiens Pennant,
      Clethrionomys glareolus [Schreber], Microtus agrestis [L.], Apodemus sylvaticus
      [L.], A. flavicollis [Melchior], Lepus europaeus Pallas, L. timidus L.) were
      found to infect feeding tick larvae with B. burgdorferi s.l., whereas two species
      of large mammals (Capreolus capreolus L., Alces alces L.) failed to infect
      feeding tick larvae with this spirochete. The most important mammalian reservoirs
      at the study locality were S. araneus and rodents, accounting for 91% of all I.
      ricinus larvae infected. In view of the great number of potentially effective
      reservoirs for B. burgdorferi s.l. in Sweden, control of Lyme disease by
      reduction of abundance of reservoir hosts will be difficult to achieve. We also
      found that infectivity of a rodent species is related to the number of infesting,
      potentially infective nymphal I. ricinus. Insectivores and rodents were the most
      important hosts of larval I. ricinus, whereas most nymphal ticks fed on hares and
      cervids. Adult I. ricinus were frequently found on all species of hares and
      cervids examined but never on insectivores and rodents. No single species seemed
      to be of paramount importance as a source of blood for female ticks. Therefore,
      control of Lyme disease by reduction of abundance of mammal hosts available for
      female tick engorgement will probably require massive reductions of numbers of
      both C. capreolus and L. timidus.

PMID- 7815402
TI  - New species of flea (Siphonaptera: Pulicidae) from Spain.
AB  - The male holotype and female allotype of Echidnophaga iberica Ribeiro, Lucientes,
      Osacar & Calvete, a new species of rabbit flea from the Zaragoza area,
      northeastern Spain, is described on the basis of examination of a type series of
      six males and 13 females. Similarities of the new species with other species of
      the genus Echidnophaga are discussed and a key to identification of the four
      known Mediterranean species of the genus is provided.

PMID- 7815403
TI  - Histologic detection of multiple blood meals in Phlebotomus duboscqi (Diptera:
      Psychodidae).
AB  - A histologic technique was used to detect multiple hamster blood meals taken by
      Phlebotomus duboscqi Neveu-Lemaire during a 5-d period. Forty-eight flies were
      fed two or three blood meals separated by 48, 72, or 120 h and sampled
      immediately; multiple meals were detected in 27 flies (56%). Double meals
      separated by 72 h within a single gonotrophic cycle were documented in 11/19
      (58%) flies; double meals separated by 120 h were detected in only 4/17 (24%)
      flies. Triple blood meals taken at 0, 72, and 120 h were detected in 5/12 (42%)
      flies; all of these flies contained the second and third meals. Early blood meals
      were detected clearly within later blood meals as a delimited body of dark
      digested blood, heme (sometimes also with pink undigested blood), the presence of
      an associated pale pink-staining peritrophic plug, the presence and appearance of
      the peritrophic membrane surrounding the meals, and a physical space between
      meals; the first two characteristics were the most important. Development of the
      ovarian follicles including apparent dilatations was also observable using this
      histologic technique. The results of this study indicate that the rate of
      multiple feeding can be determined using histology. The technique would be useful
      in evaluating the blood feeding frequency of field-caught sand flies in endemic
      areas of leishmaniasis, bartonellosis, and phleboviruses.

PMID- 7815404
TI  - Sexual dimorphism and developmental change of the salivary glands in adult
      Culicoides variipennis (Diptera: Ceratopogonidae).
AB  - Salivary glands of adult male and female Culicoides variipennis (Coquillett) were
      sexually dimorphic when examined by phase contrast light microscopy. Female
      salivary glands were larger and more complex than those in males. Each female
      gland consisted of a main gland, which was subdivided into a proximal neck and a
      distal body with reference to the salivary duct, and four accessory glands. Each
      male salivary gland consisted of a pear-shaped body with a constriction, or neck,
      that divided it into a proximal and a distal portion, with reference to the
      salivary duct. Salivary glands of both sexes increased in length from emergence
      to day 3, followed by a sex-specific pattern of decrease. Based on these
      morphological observations, we suggest that the salivary glands of female C.
      variipennis are specialized in the production of secretory materials for blood
      feeding.

PMID- 7815405
TI  - Complex interactions between vectors and pathogens: Culicoides variipennis
      sonorensis (Diptera: Ceratopogonidae) infection rates with bluetongue viruses.
AB  - Two laboratory colonies of Culicoides variipennis sonorensis Wirth & Jones were
      allowed to take blood meals containing the five U.S. serotypes (2, 10, 11, 13,
      and 17) of bluetongue (BLU) virus. After 14 d of extrinsic incubation, the flies
      were assayed for the presence of virus using an antigen capture enzyme-linked
      immunosorbent assay (ELISA). There was a significant effect of the serotype on
      infection of C. v. sonorensis with BLU virus. There was no significant difference
      in infection of the two colonies when averaged across the five BLU virus
      treatments. However, there was a statistically significant interaction between
      the colonies and the virus serotypes, which was demonstrated by a higher rate of
      infection of the AA colony with BLU virus serotype 13 and a higher rate of
      infection of the AK colony with BLU virus serotype 11.

PMID- 7815406
TI  - Anticoagulant activity in salivary gland extracts of black flies (Diptera:
      Simuliidae).
AB  - Anticoagulant activity was determined in salivary gland extracts from four
      species of black flies, i.e., Simulium vittatum Zetterstedt, Simulium argus
      Williston, Simulium metallicum Bellardi, and Simulium ochraceum Walker.
      Inhibition of coagulation factor Xa occurred among all four, whereas thrombin
      inhibition was detected in S. argus and S. vittatum only. Both bovine and human
      alpha-thrombins were inhibited with the highest activity occurring with S. argus
      salivary gland extracts. Factor Xa inhibition was highest in S. ochraceum, an
      anthropophilic species and vector of Onchocerca volvulus, and lowest in S.
      vittatum, a primiparous autogenous species that is also zoophilic. Total soluble
      salivary gland extract protein also varied among the four species with the
      highest concentration measured in S. ochraceum and the lowest in S. vittatum. A
      positive correlation was observed between the amount of soluble protein and
      percentage of inhibition of factor Xa for the four species.

PMID- 7815407
TI  - Phlebotomines (Diptera: Psychodidae) collected at a Costa Rican dairy farm in a
      vesicular stomatitis endemic area.
AB  - This study determined the species composition of sand flies in a vesicular
      stomatitis endemic area, at Carrizal, Alajuela, Costa Rica. Eight species were
      collected as follows: Lutzomyia volcanensis (Fairchild & Hertig), L. shannoni
      (Dyar), Lu. pia (Fairchild & Hertig), L. sanguinaria (Fairchild & Hertig), L.
      youngi Feliciangeli & Murillo, L. longipalpis (Lutz & Neiva), L. serrana
      (Damasceno & Arouck), and L. gomezi (Nitzulescu).

PMID- 7815409
TI  - Spatial stability of Aedes vigilax (Diptera: Culicidae) eggshells in southeastern
      Queensland salt marshes.
AB  - Sampling was done to examine whether eggshells of the saltmarsh mosquito, Aedes
      vigilax (Skuse), remained near the oviposition site or were dispersed by tidal
      flow. Few eggshells were found in the water column during tidal floodings or
      accumulated in the basins of small ponds when compared with pond banks, which is
      the oviposition site of A. vigilax. These data indicated that relatively few
      eggshells were flushed by rain or tides and that eggshell sampling can be used to
      pinpoint oviposition sites and, potentially, to focus larval control efforts
      within a salt marsh.

PMID- 7815408
TI  - Ectoparasites of opossums and raccoons in southeastern Georgia.
AB  - Twelve species of ectoparasites (four fleas, three ticks, three chiggers, one
      macronyssid mite, and one atopomelid mite) were recovered from 42 opossums,
      Didelphis virginiana Kerr, live-trapped from September 1992 through April 1994 in
      southeastern Georgia. The fleas, Ctenocephalides felis (Bouche) (prevalence =
      19%) and Polygenis gwyni (C. Fox) (36%); the ticks, Dermacentor variabilis (Say)
      (40%) and Ixodes scapularis Say (19%); and the macronyssid mite, Ornithonyssus
      wernecki (Fonseca) (21%), exhibited the highest infestation prevalences on
      opossums. The atopomelid mite, Didelphilichus serrifer Fain, and the chigger mite
      Leptotrombidium peromysci Vercammen-Grandjean & Langston, both ectoparasites of
      opossums, are reported from Georgia for the first time. Six species of
      ectoparasites (one chewing louse, four ticks, and one macronyssid mite) were
      collected from 58 raccoons, Procyon lotor (L.), examined between October 1992 and
      September 1993 in the same region. The chewing louse, Trichodectes octomaculatus
      Paine (prevalence = 24%); and the ticks, Amblyomma americanum (L.) (69%), D.
      variabilis (55%), and Ixodes texanus Banks (24%), exhibited the highest
      infestation prevalences on raccoons. Three species of ticks, A. americanum, D.
      variabilis, and I. scapularis, were the only ectoparasites recovered from both
      host species. Several of the ectoparasites collected are proven vectors of
      pathogenic agents that affect humans and animals.

PMID- 7815410
TI  - Salivarectomy effects on the ingestion of Brugia pahangi (Nematoda: Filarioidea)
      microfilariae by susceptible and refractory strains of Aedes aegypti (Diptera:
      Culicidae).
AB  - Ingestion of Brugia pahangi Buckley & Edeson microfilariae by susceptible
      (Liverpool) and refractory (Bora-Bora) strains of salivary duct-severed Aedes
      aegypti (L.) was investigated. The transection at either the salivary common duct
      or the two lateral ducts of mosquitoes did not affect the mean number of
      microfilariae nor the mean amount of blood ingested per mosquito. These results
      indicated that mosquito salivary secretion did not have a chemotropic effect on
      microfilariae.

PMID- 7815411
TI  - Black widow spider Latrodectus cinctus (Araneae: Theridiidae) new to Liberia-
      savanna species in the forest zone.
AB  - The first record of the African black widow spider, Latrodectus cinctus
      Blackwall, 1865 (= L. indistinctus Pickard-Cambridge, 1904) from Liberia is
      presented. It is a further record of a savanna species in the forest zone of West
      Africa. Increasing deforestation may cause expansion of the ranges of savanna
      inhabiting animal species into the forest zone.

PMID- 7815412
TI  - Scanning electron microscopy of the egg of Mansonia dives (Diptera: Culicidae).
AB  - The egg of Mansonia dives (Schiner) is described by means of scanning electron
      micrographs and compared with other species described in previous studies. The
      egg of Ma. dives differs from those of Ma. uniformis (Theobald), Ma. indiana
      (Edwards), Ma. annulifera (Theobald), Ma. annulata (Leicester), and Ma. bonneae
      (Edwards) in that it has a tuberculated anterior cup. A key for identification of
      the eggs of the six Mansonia species, based on electron microscopy, is presented.

PMID- 7815413
TI  - Isolations of West Nile and Bagaza viruses from mosquitoes (Diptera: Culicidae)
      in central Senegal (Ferlo).
AB  - During October-November 1990, 31,497 mosquitoes consisting of 25 different
      species were collected in Barkedji, Ferlo area (Senegal), and tested for virus
      infection. Viruse were isolated from 55 of 407 pools. Eighteen pools were found
      positive for both Bagaza virus (BGA) and West Nile virus (WN). One alphavirus
      (Babanki [BBK] and 72 flaviviruses (19 BGA, 53 WN) were isolated from Culex
      poicilipes Theobald (29 WN, 8 BGA), C. neavei Theobald (3 WN, 1 BGA), Mimomyia
      hispida Theobald (8 WN, 6 BGA, and 1 BBK), M. lacustris Edwards (4 WN, 1 BGA), M.
      splendens Theobald (6 WN, 2 BGA), Mimomyia. spp. (2 WN), and Aedeomyia africana
      Neveu-Lemaire (1 WN). These were the first isolations of arboviruses from A.
      africana and Mimomyia species. C. poicilipes and possibly Mimomyia spp. may be
      involved in an avian-mosquito cycle of West Nile virus transmission in Senegal.

PMID- 7815414
TI  - Inv dup(15) supernumerary marker chromosomes.

PMID- 7815415
TI  - Anticipation resulting in elimination of the myotonic dystrophy gene: a follow up
      study of one extended family.
AB  - We have re-examined an extended myotonic dystrophy (DM) family, previously
      described in 1955, in order to study the long term effects of anticipation in DM
      and in particular the implications for families affected by this disease. This
      follow up study provides data on 35 gene carriers and 46 asymptomatic at risk
      family members in five generations. Clinical anticipation, defined as the cascade
      of mild, adult, childhood, or congenital disease in subsequent generations,
      appeared to be a relentless process, occurring in all affected branches of the
      family. The cascade was found to proceed asynchronously in the different
      branches, mainly because of an unequal number of generations with mild disease.
      The transition from the mild to the adult type was associated with transmission
      through a male parent. Stable transmission of the asymptomatic/mild phenotype
      showed a female transmission bias. We further examined the extent and causes of
      gene loss in this pedigree. Gene loss in the patient group was complete, owing to
      infertility of the male patients with adult onset disease and the fact that
      mentally retarded patients did not procreate. Out of the 46 at risk subjects in
      the two youngest generations, only one was found to have a full mutation. This is
      the only subject who may transmit the gene to the sixth generation. No
      protomutation carriers were found in the fourth and fifth generations. Therefore
      it is highly probable that the DM gene will be eliminated from this pedigree
      within one generation. The high population frequency of DM can at present not be
      explained by the contribution of asymptomatic cases in the younger generations of
      known families, but is probably caused by the events in the ancestral
      generations.

PMID- 7815416
TI  - Long segment and short segment familial Hirschsprung's disease: variable clinical
      expression at the RET locus.
AB  - Hirschsprung's disease (aganglionic megacolon, HSCR) is a frequent condition of
      unknown origin (1/5000 live births) resulting in intestinal obstruction in
      neonates and severe constipation in infants and adults. In the majority of cases
      (80%), the aganglionic tract involves the rectum and the sigmoid colon only
      (short segment HSCR), while in 20% of cases it extends toward the proximal end of
      the colon (long segment HSCR). In a previous study, we mapped a gene for long
      segment familial HSCR to the proximal long arm of chromosome 10 (10q11.2).
      Further linkage analyses in familial HSCR have suggested tight linkage of the
      disease gene to the RET protoncogene mapped to chromosome 10q11.2. Recently,
      nonsense and missense mutations of RET have been identified in HSCR patients.
      However, the question of whether mutations of the RET gene account for both long
      segment and short segment familial HSCR remained unanswered. We have performed
      genetic linkage analyses in 11 long segment HSCR families and eight short segment
      HSCR families using microsatellite DNA markers of chromosome 10q. In both
      anatomical forms, tight pairwise linkage with no recombinant events was observed
      between the RET proto-oncogene locus and the disease locus (Zmax = 2.16 and Zmax
      = 5.38 for short segment and long segment HSCR respectively at 0 = 0%) Multipoint
      linkage analyses performed in the two groups showed that the maximum likelihood
      estimate was at the RET locus. Moreover, we show that point mutations of the RET
      proto-oncogene occur either in long segment or in short segment HSCR families and
      we provide evidence for incomplete penetrance of the disease causing mutation.
      These data suggest that the two anatomical forms of familial HSCR, which have
      been separated on the basis of clinical and genetic criteria, may be regarded as
      the variable clinical expression of mutations at the RET locus.

PMID- 7815417
TI  - Parental origin of transcription from the human GNAS1 gene.
AB  - Variation in the phenotypic expression of Albright's hereditary osteodystrophy
      (AHO) determined by the parent of transmission, suggests that the human Gs alpha
      gene (GNAS1), in which mutations occur in AHO, may be under imprinted control.
      GNAS1 is also known to map to a chromosomal region (20q13.11) showing syntenic
      homology with the imprinted mouse region 2E1-2H3. To establish if GNAS1 is indeed
      imprinted, we have examined the parental origin of GNAS1 transcription in human
      fetal tissues. Of 75 fetuses genotyped, at gestational ages ranging from 6 to 13
      weeks, 13 heterozygous for a FokI polymorphism in exon 5 of GNAS1 were identified
      whose mothers were homozygous for one or other allele. RNA from up to 10
      different tissues from each fetus was analysed by RT-PCR. In all cases expression
      from both parental alleles was shown by FokI digestion of RT-PCR products and
      quantification of the resulting fragments. No tissue specific pattern of
      expression was discerned in these experiments. If genomic imprinting regulates
      the expression of the human GNAS1 gene, our data suggest that the effect must
      either be subtle and quantitative, or be confined to a small subset of
      specialised hormone responsive cells within the target tissues.

PMID- 7815418
TI  - First trimester prenatal diagnosis of Menkes disease by DNA analysis.
AB  - Menkes disease is an X linked recessive disorder of copper metabolism
      characterised by neurological symptoms and connective tissue manifestations. The
      defective gene in Menkes disease has recently been isolated and the gene product
      is predicted to be a copper transporting ATPase. The diagnosis of Menkes disease
      has hitherto been performed by biochemical analysis, based on intracellular
      accumulation of copper. Cloning the gene opened up the possibility of
      establishing precise and reliable carrier and prenatal diagnosis by defining the
      molecular defect. In this report we describe the partial deletion of the Menkes
      gene in a patient who had inherited the mutation from his phenotypically normal
      mother. This information enabled us to perform prenatal diagnosis by direct
      mutation analysis of the mother's sixth pregnancy and we detected the same
      deletion, indicating that the male fetus was affected. This first prenatal
      diagnosis of Menkes disease by direct mutation analysis shows some advantages of
      DNA analysis compared to biochemical diagnosis.

PMID- 7815419
TI  - Neoplastic diseases in families of breast cancer patients.
AB  - OBJECTIVE: To investigate whether the risk of cancer at all sites, and at
      individual sites other than breast, prostate, ovaries, and endometrium, is
      increased among relatives of breast cancer patients compared with the general
      population. DESIGN: A cohort of family members of breast cancer patients was
      established. The probands were chosen by year of birth or time of diagnosis. Any
      influence of knowledge of the cancer experience of the relatives has been
      avoided. The risk estimates are based on expected numbers computed from age and
      time specific incidence rates for the Icelandic population. SETTING: Iceland.
      SUBJECTS: The population of Iceland. MAIN OUTCOME MEASURES: Relative risks by
      degree of relatedness and age of proband. RESULTS: The relative risk of cancer at
      all sites is raised for males and females. This is more than expected based on
      the known familial risk of breast cancer, prostate, and ovarian cancer. The
      excess risk of breast, prostate, and ovarian cancer is confirmed, but not that of
      cancer of the endometrium. The risk of cancer of the pancreas in both sexes and
      the stomach and kidneys in females is significantly raised. No evidence was found
      for decreased risk for any cancer type. CONCLUSIONS: The risk of cancer at all
      sites in relatives of breast cancer patients is increased. In addition to the
      risk of breast, prostate, and ovarian cancer, the risk of pancreas cancer and
      cancer of the stomach and kidneys in females is raised, but the last mentioned
      observations need further confirmation.

PMID- 7815421
TI  - Muir-Torre syndrome: a variant of the cancer family syndrome.
AB  - Muir-Torre syndrome is characterised by the association of sebaceous tumours of
      the skin with internal malignancy. In many instances there is a strong family
      history of cancer and the autosomal dominant mode of inheritance, tumour
      spectrum, and high incidence of synchronous and metachronous tumours show
      parallels with the cancer family syndrome or Lynch II syndrome. We report a five
      generation family with at least two persons displaying the Muir-Torre phenotype,
      while many other family members have had tumours consistent with cancer family
      syndrome. The majority of tumours are gastrointestinal, gynaecological, and
      urological, with several persons having multiple primaries. The prognosis appears
      to be better than would be expected. Sebaceous tumours are a marker for internal
      malignancy and should prompt a search for occult cancer in the individual person
      and family members. In documented Muir-Torre families, at risk persons should be
      entered into screening programmes similar to those used in the Lynch II syndrome.

PMID- 7815420
TI  - Apolipoprotein CII-Padova (Tyr37-->stop) as a cause of chylomicronaemia in an
      Italian kindred from Siculiana.
AB  - In this paper we report on the molecular defect underlying apolipoprotein CII
      (apoCII) deficiency in an Italian kindred. ApoCII serves as cofactor for
      lipoprotein lipase (LPL) in triglyceride hydrolysis of chylomicrons and very low
      density lipoproteins. Homozygous apoCII deficiency manifests with type I
      hyperlipoproteinaemia and is a rare disorder of lipoprotein metabolism. Until
      now, only 10 kindreds with apoCII deficiency have been published and all
      underlying mutations were unique. The proband was the offspring of a
      consanguineous mating. Sequencing of cloned DNA from the proband presented in
      this report showed homozygosity for a C-->A substitution at position 3002 in the
      apoCII gene, resulting in the introduction of a premature stop codon at residue
      37 of the mature apoCII protein. Therefore, a truncated apoCII is synthesised,
      lacking the part of the apolipoprotein that activates LPL. This mutation has
      previously been described in another Italian family and is known as apoCIIPadova.
      We propose that apoCIIPadova is a frequent cause of apoCII deficiency in persons
      of Italian descent.

PMID- 7815423
TI  - Congenital contractural arachnodactyly (Beals syndrome).
AB  - Congenital contractural arachnodactyly (CCA) is an autosomal dominant disorder
      akin to, but usually less severe than, Marfan syndrome. The clinical features are
      marfanoid habitus, arachnodactyly, crumpled ears, camptodactyly of the fingers
      and adducted thumbs, mild contractures of the elbows, knees, and hips, and mild
      muscle hypoplasia especially of the calf muscles. Many patients have
      kyphoscoliosis and mitral valve prolapse and, very occasionally, aortic root
      dilatation and ectopia lentis have been described. Linkage to a gene coding for
      fibrillin on chromosome 5q23-31 has been shown in several kindreds. The prognosis
      for a normal lifespan is good and improvement in joint contractures is usual.

PMID- 7815422
TI  - Facial morphometry of Ecuadorian patients with growth hormone receptor
      deficiency/Laron syndrome.
AB  - Facial morphometry using computerised image analysis was performed on patients
      with growth hormone receptor deficiency (Laron syndrome) from an inbred
      population of southern Ecuador. Morphometrics were compared for 49 patients, 70
      unaffected relatives, and 14 unrelated persons. Patients with growth hormone
      receptor deficiency showed significant decreases in measures of vertical facial
      growth as compared to unaffected relatives and unrelated persons with short
      stature from other causes. This report validates and quantifies the clinical
      impression of foreshortened facies in growth hormone receptor deficiency.

PMID- 7815424
TI  - Maternal uniparental disomy of chromosome 13 in a phenotypically normal child.
AB  - A case of maternal uniparental disomy of chromosome 13 is described. The subject
      is a phenotypically normal male who inherited a t(13;13)(p11.2;p11.2) from his
      mother who is a carrier of this translocation. The mother was ascertained through
      a history of recurrent abortion and is phenotypically normal. The translocation
      in both subjects was studied by cytogenetic and DNA analysis and appears to be a
      true dicentric isochromosome. These findings show that maternal uniparental
      disomy of chromosome 13 has had no pathological consequences and suggests that
      there is no imprinting of genes on maternally derived chromosome 13.

PMID- 7815425
TI  - Blepharophimosis sequence and diaphragmatic hernia associated with interstitial
      deletion of chromosome 3 (46,XY,del(3)(q21q23)).
AB  - A case of blepharophimosis, ptosis, and epicanthus inversus (BPES) associated
      with prenatally diagnosed diaphragmatic hernia and interstitial deletion of the
      long arm of chromosome 3, del(3)(q21q23), is reported. Comparison with other
      cases of BPES resulting from 3q rearrangements indicate that this disorder,
      previously assigned to 3q2, can now be more accurately mapped to 3q23.

PMID- 7815426
TI  - X;Y translocation in a girl with short stature and some features of Turner's
      syndrome: cytogenetic and molecular studies.
AB  - A 13 year old girl referred for chromosome analysis because of disproportionate
      short stature (short neck, curved legs, pectus excavatum) with an initial
      clinical diagnosis of Turner's syndrome was found to have the karyotype 46,X, +
      der(X) in 100% of her blood lymphocytes. By means of conventional differential
      staining (QFH/AcD, FPG, and RBA banding) supplemented with distamycin A
      treatment, the karyotype of the proband was interpreted as 46,X,t(X;Y)
      (p22.3;q11). The rearranged marker X chromosome was found to be active in 91% of
      lymphocytes studied. PCR analysis with Y chromosome specific oligoprimers showed
      the presence of some Y chromosome long arm DNA in both lymphocyte and gonadal
      tissue biopsy cells. At laparoscopy the patient was found to have small gonads
      with a rudimentary uterus and fallopian tubes. Histological examination of
      gonadal tissue showed primary follicles with dystrophic changes of the germ cells
      and numerous follicular cysts (polycystic ovaries). The proband's phenotype and
      its correlation with the genetic imbalance of the rearranged X chromosomes, as
      well as with non-random t(X;Y) chromosome inactivation, are briefly discussed.

PMID- 7815427
TI  - Partial trisomy for 2q in a patient with dir dup(2) (q33.1q35).
AB  - A 22 year old woman with partial trisomy for the long arm of chromosome 2 is
      described. The karyotype is 46,XX, dir dup(2)(q33.1q35) de novo confirmed by FISH
      using a chromosome 2 specific paint. Parental chromosome studies were normal. To
      our knowledge this is the first report of trisomy for this specific segment of 2q
      and only the sixth case of de novo direct duplication of 2q, one of which was
      mosaic. Clinical features include epicanthus, clinodactyly, scoliosis, broad,
      flat nasal bridge, thin upper lip, long philtrum, and short neck.

PMID- 7815428
TI  - Chemiluminescent detection of blotted PCR products (CB-PCR) of two CAG dynamic
      mutations (Huntington's disease and spinocerebellar ataxia type 1).
AB  - We have used a non-isotopic PCR assay based on the chemiluminescent detection of
      blotted PCR products (CB-PCR) for two dynamic mutation diseases (Huntington's
      disease and spinocerebellar ataxia type 1). This gives an accurate sizing of
      alleles and permits a rapid analysis of at risk persons. The system involves PCR
      of the samples, separation of alleles on polyacrylamide gels, Southern blotting,
      and hybridisation with specific primers 3' labelled with fluorescein (F1)-dUTP as
      probes. CB-PCR retains the isotopic sensitivity for accurate allele
      determination, avoids isotopic manipulation, and provides the advantages of
      safety, long term storage of probes, and recycling of hybridisation solutions.

PMID- 7815429
TI  - Expanded CAG trinucleotide repeat of Huntington's disease gene in a patient with
      schizophrenia and normal striatal histology.

PMID- 7815430
TI  - Further family with autosomal dominant patent ductus arteriosus.

PMID- 7815431
TI  - Molecular basis of the common electrophoretic polymorphism (Fu1/Fu2) in human
      alpha-L-fucosidase.

PMID- 7815432
TI  - The arylsulphatase A gene and molecular genetics of metachromatic leucodystrophy.

PMID- 7815433
TI  - Frequency of arylsulphatase A pseudodeficiency associated mutations in a healthy
      population.
AB  - Arylsulphatase A (ASA, EC 3.1.6.1) is a lysosomal enzyme that catalyses
      cerebroside sulphate degradation. ASA deficiency is associated with metachromatic
      leucodystrophy (MLD), a rare autosomal recessive disorder, which is characterised
      by the storage of cerebroside sulphate. Low ASA activities can be also observed
      in clinically healthy persons, a condition termed ASA pseudodeficiency. Two
      mutations responsible for the majority of pseudodeficiency alleles have been
      defined in the ASA gene. These are both A-->G transitions. One causes an
      asparagine to serine substitution (N350S). The second changes the first
      polyadenylation signal downstream of the stop codon (1524 + 95A-->G), which
      causes a severe deficiency of one ASA mRNA species. The incidence of the
      pseudodeficiency allele is estimated to be high in the general population and can
      be found in families carrying MLD associated mutations. We report a reliable
      stratagem for detecting the two PD associated mutations separately, which we have
      applied to a healthy population. Two homozygotes for the N350S and 1524 + 95A-->G
      mutations were detected, which gives a population frequency of 2.6%. The overall
      frequencies of the ASA-PD mutations were shown to be 17.5% for the N350S change
      and 13.0% for the 1524 + 95A-->G change, estimating each mutation separately. In
      addition, the frequency of both PD associated mutations occurring together on the
      same chromosome was found to be 12.3% in our population. The study has also
      allowed us to establish a new control ASA activity range, which was based on
      assay of blood from persons who had been shown at the DNA level not to carry ASA
      PD associated mutations.

PMID- 7815434
TI  - A single origin for the most frequent mutation causing late infantile
      metachromatic leucodystrophy.
AB  - Metachromatic leucodystrophy is an autosomal recessive degenerative disease of
      the nervous system caused by the deficiency of the lysosomal enzyme
      arylsulphatase A (ARSA). We report here on the high incidence of late infantile
      MLD among Muslim Arabs originating from Jerusalem, most probably because of a
      founder effect. All the patients were found to be homozygous for 459 + 1 G-->A, a
      mutation which destroys the splice donor site of exon 2 of the ARSA gene. This
      mutation has been reported to be the most common mutation causing MLD. We studied
      the ARSA haplotype defined by three intragenic polymorphic sites in DNA samples
      from Muslim Arab patients from Jerusalem, a Christian Arab patient originating
      from the region, and eight other white patients, all homozygous for the 459 + 1 G
      ->A mutation. All the alleles carried the same haplotype which is in complete
      linkage disequilibrium with the mutation. This finding indicates a common origin
      for the 459 + 1 G-->A mutation which may have been introduced into Jerusalem at
      the time of the Crusades.

PMID- 7815435
TI  - FISH detection of trisomy 21 in interphase by the simultaneous use of two
      differentially labelled cosmid contigs.
AB  - Techniques have been reported in which fluorescence in situ hybridisation (FISH)
      and cosmid probes are used to detect trisomy 21 (and other abnormalities
      involving chromosomes X, Y, 13, and 18) on uncultured amniocytes. However the
      detection rate of trisomy 21 is lower than for the other anomalies owing to a
      larger number of uninformative results and false negatives. We report the
      simultaneous use of two differentially labelled cosmid contigs to improve the
      detection rate of trisomy 21 on uncultured amniocyte samples thus allowing the
      prenatal diagnosis of Down's syndrome even if only few labelled nuclei are
      available.

PMID- 7815436
TI  - Anticipation in Swedish families with bipolar affective disorder.
AB  - Anticipation describes an inheritance pattern within a pedigree with an increase
      in disease severity or decrease in age at onset or both in successive
      generations. The phenomenon of anticipation has recently been shown to be
      correlated with the expansion of trinucleotide repeat sequences in different
      disorders. We have studied differences of age at onset and disease severity
      between two generations in 14 families with unilinear inheritance of bipolar
      affective disorder (BPAD). There was a significant difference in age at onset (p
      < 0.008), in episodes per year with (p < 0.006) and without (p < 0.03) lithium
      treatment, and in total episodes per year (p < 0.002) between generations I and
      II. Furthermore, there was a highly significant correlation (p < 0.001) in age at
      onset between generations I and II. No evidence for specific paternal or maternal
      inheritance was found. We found evidence of anticipation and could rule out
      ascertainment bias or some other artefact. Anticipation is thus an inheritance
      pattern in BPAD which suggests that the expansion of trinucleotide repeat
      sequences is a possible mode of inheritance in BPAD.

PMID- 7815437
TI  - Study of the Huntington's disease (HD) gene CAG repeats in schizophrenic patients
      shows overlap of the normal and HD affected ranges but absence of correlation
      with schizophrenia.
AB  - The CAG repeats in the Huntington's disease gene were investigated in chromosomes
      from 71 unrelated schizophrenic persons and 18 patients with schizoaffective
      disorder in order to determine if any of these patients had abnormal expansions.
      All of the probands had repeat sizes in the normal range (< 35 repeats) and there
      was no significant difference between the allele distributions of these patients
      and the normal controls. The families of two patients with 32 repeats and one
      patient with 34 repeats were investigated further and showed no uniform
      segregation of the disease with the large repeat alleles. The proband with 34
      repeats inherited a chromosome that originally had 36 repeats in her father. The
      presence of 36 CAG repeats in members of her family and in HD patients suggests
      that there is an overlap between the normal and Huntington's disease CAG repeat
      size ranges. The more recently described CCG polymorphism in this gene was also
      examined in the schizophrenic and schizoaffective persons. All patients had
      alleles in the normal range.

PMID- 7815438
TI  - Asymmetry and skin pigmentary anomalies in chromosome mosaicism.
AB  - We report six persons mosaic for a chromosome anomaly. All were mentally retarded
      and dysmorphic. Unilateral or asymmetrical features were found in all cases, in
      one an unusual transverse terminal limb anomaly, and in the others various
      degrees of hemiatrophy of the left side of the body. Five of the subjects had
      skin pigmentary anomalies which were distributed in the lines of Blaschko. The
      abnormal cell lines found were ring chromosome 22, trisomy 22, a large
      acrocentric marker, a deletion of 18q, a deletion of 8q, and triploidy. In four
      cases the clinical diagnosis was only confirmed by skin biopsy. In one case low
      level mosaicism in blood was fortuitously detected because of cytogenetic fragile
      X screening and confirmed in a skin biopsy. The sixth case was of dynamic
      mosaicism of a non-mosaic deletion 18q with a chromosome 18 derived marker
      present in a proportion of cells. Chromosome mosaicisn may cause subtle and
      asymmetrical clinical features and can require repeated cytogenetic
      investigations. The diagnosis should be actively sought as it enables accurate
      genetic counselling to be given.

PMID- 7815439
TI  - Genetic epidemiology of single gene defects in Chile.
AB  - We have studied the correlation between the ethnic structure and the prevalence
      of single gene defects in Chile. At present the Chilean population is
      approximately 64% white and 35% Amerindian with traces of other admixture. Fewer
      than 4% of the Chilean population are foreign born. Investigations indicate that
      all severe diseases and many others without impaired reproduction have mutation
      rates within the range of the white population. Classical ethnic diseases are
      very rare. Autosomal recessive disorders have a wide range of variability: cystic
      fibrosis has a low incidence and PKU has a similar incidence to English rates.
      Only 30% of the inborn errors of metabolism have been described in Chilean
      medical publications. In addition, no Chilean haemoglobin or haptoglobin variants
      have been described. Some rare inherited diseases in Chilean human isolates have
      been described, including achromatopsia, chondrocalcinosis, and Creutzfeldt-Jakob
      disease. The prevalence of intrahepatic cholestasis of pregnancy and
      supernumerary nipples is the highest in the world and they are associated with
      aboriginal origin. Single gene defects in Chile are probably shaped by factors
      related to its ethnic population structure. These local rare single gene defects
      may be good markers of population admixture for genetic epidemiological studies.

PMID- 7815440
TI  - Mulvihill-Smith syndrome: case report and review.
AB  - We report a 20 year old man with short stature, microcephaly, unusual facies,
      numerous pigmented naevi, hypodontia, immunodeficiency, and a high pitched voice.
      Tympner et al had assumed that the patient had a new syndrome of "progressive
      combined immunodeficiency and ectomesodermal dysplasia". We show here that the
      condition is identical to the Mulvihill-Smith syndrome (McKusick 176690), a
      progeroid disorder described in four or possibly five sporadic cases to date. We
      describe his clinical progress up to the age of 20 years. Our patient suffered
      from severe viral infections, allergic rhinitis and conjunctivitis, delayed
      puberty, visual loss, modest achievement in high school, and reactive depression.
      The immunological, facioskeletal, and dental abnormalities are presented in
      detail.

PMID- 7815441
TI  - Familial half cryptic translocation t(9;17).
AB  - A half cryptic translocation t(9;17) (p24.2; p13.3) was detected in a large
      family by fluorescence in situ hybridisation. Unbalanced karyotypes resulted
      either in lissencephaly and early death or in mental retardation, microcephaly,
      high arched palate, and deformities of the vertebrae. Some of the features
      observed in affected persons are characteristic of known syndromes involving
      either 17p or 9p.

PMID- 7815442
TI  - Homozygosity for a new mutation (Ile119-->Met) in the insulin receptor gene in
      five sibs with familial insulin resistance.
AB  - Mutations in the insulin receptor gene can cause genetic syndromes such as
      leprechaunism that are associated with extreme insulin resistance. We have
      investigated a patient with leprechaunism born of a consanguineous marriage. All
      22 exons of the insulin receptor gene were screened for mutations using
      denaturing gradient gel electrophoresis. Thereafter, the nucleotide sequences of
      selected exons were determined directly. The patient was homozygous for a point
      mutation in exon 2 of the insulin receptor gene which results in the substitution
      of methionine for isoleucine at codon 119. Thus, the mutant allele encodes a
      receptor that has a mutation in the putative insulin binding domain. Accordingly,
      the mutant receptor would be predicted not to transduce the insulin signal
      effectively. In spite of a homozygous abnormality of the insulin receptor gene
      and many of the clinical features of severe insulin resistance, the proband's
      clinical syndrome was noticeably different from previously described patients
      with leprechaunism who usually die within the first six months of life. There are
      a total of nine children in the family, five of whom are homozygous for the
      Ile119-->Met mutation in the insulin receptor gene, and are clinically affected
      with varying degrees of severity. Four unaffected sibs are clinically normal; two
      are heterozygous carriers of the mutant allele, one is homozygous for the normal
      allele, and one unaffected sib was not available for molecular studies.

PMID- 7815443
TI  - Trisomy X in a female member of a family with X linked severe combined
      immunodeficiency: implications for carrier diagnosis.
AB  - We describe a family affected by X linked severe combined immunodeficiency
      (SCIDX1) in which genetic prediction of carrier status was made using X
      chromosome inactivation studies together with limited genetic linkage analysis.
      Linkage studies in this family showed a confusing pattern of inheritance for the
      X chromosome. A female with a random pattern of X chromosome inactivation in her
      T cells appeared to have inherited an X chromosome with four recombinations
      within 10 cM. The odds of this happening in a single meiotic event make this an
      unlikely explanation. Data obtained from studying the X chromosomes of her two
      unaffected sons showed that this could be explained simply on the basis of her
      having inherited three alleles each of the relevant polymorphic DNA loci. We used
      fluorescent in situ hybridisation (FISH) to confirm that this person had
      inherited three complete X chromosomes. Thus, although the results from X
      chromosome inactivation analysis indicated that this subject was not a carrier of
      the affected chromosome, FISH and genetic linkage analysis showed clearly that
      the affected chromosome had been inherited. The implications of this finding for
      diagnosis of carrier status in this family and for other families with X linked
      inherited immunodeficiencies is discussed.

PMID- 7815444
TI  - Autosomal dominant simple microphthalmos.
AB  - Congenital bilateral microphthalmos is a rare malformation of the eye, which
      ranges from extreme to mild reduction of total axial length. Microphthalmos may
      occur as an isolated ocular abnormality or as part of a systemic disorder, and
      different classifications of the condition have been attempted. We describe a
      large pedigree with 14 persons in four generations affected with bilateral
      microphthalmos without other ocular or systemic signs. An autosomal dominant
      trait with complete penetrance is proposed. Five subjects underwent a complete
      ophthalmological evaluation. The total axial length was measured by A scan
      ultrasonography in all persons. Ultrasonography showed a reduction of the total
      axial length (range 18.4-19.7 mm) and a reduced vitreous cavity length (range
      11.4-13.5 mm) in all investigated patients. All the patients had microcornea
      (range 8-9.7 mm). No other ocular anomalies or associated systemic malformations
      were found. A review of published reports also suggests that simple, partial,
      posterior, pure microphthalmos and nanophthalmos are similar clinical entities
      sharing total axial length and vitreous cavity length reduction. Therefore, the
      term simple microphthalmos is proposed to identify these clinical conditions.

PMID- 7815445
TI  - Cleft hand/foot: clinical and developmental aspects.
AB  - Isolated limb reduction defects occur in approximately 1 in 2000 live births
      within which central ray anomalies are an important subgroup. Most affected
      persons have mild or moderate functional impairment. Considerable psychological
      morbidity may also occur. While there have been major strides forwards in our
      understanding of vertebrate limb development, the mechanisms responsible for
      central ray deformities remain poorly understood. Several case reports of central
      clefting anomalies associated with chromosomal rearrangements or interstitial
      deletions of 7q21.2-q21.3 suggest that this chromosomal region is important for
      limb development.

PMID- 7815446
TI  - Diaphragmatic herniae and translocations involving 8q22 in two patients.
AB  - Two girls with congenital diaphragmatic herniae are reported. Both were
      discovered to have a balanced reciprocal translocation involving 8q22.3. In one
      girl the translocation was de novo, in the other it was maternally inherited.
      Uniparental disomy was excluded in both. 8q22.3 may be the location of a gene
      affecting development of the diaphragm.

PMID- 7815447
TI  - The Pallister-Hall syndrome.

PMID- 7815448
TI  - "CATCH 22" sans cardiac anomaly, thymic hypoplasia, cleft palate, and
      hypocalcaemia: cAtch 22. A common result of 22q11 deficiency?

PMID- 7815449
TI  - Skeletal malformations and polycystic kidney disease.

PMID- 7815450
TI  - pHi regulation in Ehrlich mouse ascites tumor cells: role of sodium-dependent and
      sodium-independent chloride-bicarbonate exchange.
AB  - pHi recovery in acid-loaded Ehrlich ascites tumor cells and pHi maintenance at
      steady-state were studied using the fluorescent probe BCECF. Both in nominally
      HCO3(-)-free media and at 25 mM HCO3-, the measured pHi (7.26 and 7.82,
      respectively) was significantly more alkaline than the pHi value calculated
      assuming the transmembrane HCO3- gradient to be equal to the Cl- gradient. Thus,
      pHi in these cells is not determined by the Cl- gradient and by Cl-/HCO3-
      exchange. pHi recovery following acid loading by propionate exposure, NH4+
      withdrawal, or CO2 exposure is mediated by amiloride-sensitive Na+/H+ exchange in
      HCO3(-)-free media, and in the presence of HCO3- (25 mM) by DIDS-sensitive, Na+)
      dependent Cl-/HCO3- exchange. A significant residual pHi recovery in the presence
      of both amiloride and DIDS suggests an additional role for a primary active H+
      pump in pHi regulation. pHi maintenance at steady-state involves both Na+/H+
      exchange and Na(+)-dependent Cl-/HCO3- exchange. Acute removal of external Cl-
      induces a DIDS-sensitive, Na(+)-dependent alkalinization, taken to represent HCO3
      influx in exchange for cellular Cl-. Measurements of 36Cl- efflux into Cl(-)
      free gluconate media with and without Na+ and/or HCO3- (10 mM) directly
      demonstrate a DIDS-sensitive, Na(+)-dependent Cl-/HCO3- exchange operating at
      slightly acidic pHi (pHo 6.8), and a DIDS-sensitive, Na+)-independent Cl-/HCO3-
      exchange operating at alkaline pHi (pHo 8.2).

PMID- 7815451
TI  - The Ca-activated chloride channel of Ascaris suum conducts volatile fatty acids
      produced by anaerobic respiration: a patch-clamp study.
AB  - Plasma membrane vesicles prepared from the bag region of the somatic muscle cell
      of the parasite Ascaris suum contain a large conductance, voltage-sensitive,
      calcium-activated chloride channel. The ability of this channel to conduct a
      variety of carboxylic acids, a number of which are products of anaerobic
      respiration, was investigated using the patch-clamp technique and isolated inside
      out patches of muscle membrane. The channel has a conductance of 140 pS in
      symmetrical 140 mM chloride. Replacement of internal chloride with various
      carboxylic acids (140 mM) caused large hyperpolarizing shifts in the reversal
      potential. Permeability ratios, relative to chloride, were calculated for each
      acid. The relationship between permeability ratio and ionic size is inverse and
      linear predicting a pore diameter of 6.55 A. This simple relationship was not
      observed between ionic size and conductance. Calculation of the transition state
      energy required to transfer a single methyl group from aqueous phase to the
      binding site afforded a value that was low but favorable, indicating a cationic
      binding site of low field strength. As the channel is able to open fully at the
      resting membrane potential of Ascaris and is permeable to fatty acids produced by
      anaerobic respiration, the possible role of this channel in the removal of
      metabolic products across the muscle membrane is discussed.

PMID- 7815452
TI  - Extracellular pH determines the rate of Ca2+ entry into Madin-Darby canine kidney
      focus cells.
AB  - We investigated the relationship between intracellular Ca2+ and pH homeostasis in
      Madin-Darby canine kidney-focus (MDCK-F) cells, a cell line exhibiting
      spontaneous oscillations of intracellular Ca2+ concentration (Ca2+i). Ca2+i and
      intracellular pH (pHi) were measured with the fluorescent dyes Fura-2 and BCECF
      by means of video imaging techniques. Ca2+ influx from the extracellular space
      into the cell was determined with the Mn2+ quenching technique. Cells were
      superfused with HEPES-buffered solutions. Under control conditions (pH 7.2),
      spontaneous Ca2+i oscillations were observed in virtually all cells investigated.
      Successive alkalinization and acidification of the cytoplasm induced by an
      ammonia ion prepulse had no apparent effect on Ca2+i oscillations. On the
      contrary, changes of extracellular pH value strongly affected Ca2+i oscillations.
      Extracellular alkalinization to pH 7.6 completely suppressed oscillations,
      whereas extracellular acidification to pH 6.8 decreased their frequency by 40%.
      Under the same conditions, the respective pHi changes were less than 0.1 pH
      units. However, experiments with the Mn2+ quenching technique revealed that
      extracellular alkalinization significantly reduced Ca2+ entry from the
      extracellular space. Large increases of Ca2+i triggered by the blocker of the
      cytoplasmic Ca(2+)-ATPase, thapsigargin, had no effect on pHi. We conclude:
      intracellular Ca2+ homeostasis in MDCK-F cells is pH dependent. pH controls Ca2+
      homeostasis mainly by effects on the level of Ca2+ entry across the plasma
      membrane. On the contrary, the intracellular pH value seems to be insensitive to
      rap changes of Ca2+i.

PMID- 7815453
TI  - Concentration-dependent modulations of potassium and calcium currents of rat
      osteoblastic cells by arachidonic acid.
AB  - We show that the voltage-gated K+ and Ca2+ currents of rat osteoblastic cells are
      strongly modulated by arachidonic acid (AA), and that these modulations are very
      sensitive to the AA concentration. At 2 or 3 microM, AA reduces the amplitude and
      accelerates the inactivation of the K+ current activated by depolarization; at
      higher concentrations (> or = 5 microM), AA still blocks this K+ current, but
      also induces a very large noninactivating K+ current. At 2 or 3 microM, AA
      enhances the T-type Ca2+ current, close to its threshold of activation, whereas
      at 10 microM, it blocks that current. AA (1-10 microM) also blocks the
      dihydropyridine-sensitive L-type Ca2+ current. Thus, the effect of AA on Ca2+
      entry through voltage-gated Ca2+ channels can change qualitatively with the AA
      concentration: at 2 or 3 microM, AA will favor Ca2+ entry through T channels,
      both by lowering the voltage-gated K+ conductance and by increasing the T
      current, whereas at 10 microM, AA will prevent Ca2+ entry through voltage-gated
      Ca2+ channels, both by inducing a K+ conductance and by blocking Ca2+ channels.

PMID- 7815454
TI  - Short-term bromide uptake in skins of Rana pipiens.
AB  - Intracellular ion concentrations were determined in split skins of Rana pipiens
      using the technique of electron microprobe analysis. Based on the 1 min Br uptake
      from the apical bath, two types of mitochondria-rich (MR) cells could be
      distinguished: active cells which rapidly exchanged their anions with the apical
      bath and inactive cells which did not. Br uptake and frequency of active MR cells
      were closely correlated with the skin conductance, gt. Replacing Cl in the apical
      bath with an impermeant anion significantly lowered gt and the Br uptake and Na
      concentration of active cells. Even larger reductions were observed after apical
      amiloride (0.1 mM). The inhibition of the Br uptake was reversible by voltage
      clamping (100 mV, inside positive). Cl removal and amiloride also led to some
      shrinkage of active cells. The results suggest that the active cell is
      responsible for a large part of gt. Inactive MR cells had much lower Br and Na
      concentrations which were not significantly affected by Cl removal, amiloride, or
      voltage clamping. Principal cells, which represent the main cell type of the
      epithelium, showed only a minimal Br uptake from the apical side which was not
      correlated with gt. Moreover, Cl removal had no effect on the Na, Br, and Cl
      concentrations of principal cells.

PMID- 7815455
TI  - Sarco(endo)plasmic reticulum calcium pumps in the cardiovascular system: function
      and gene expression.

PMID- 7815456
TI  - Cardiac troponin I and tension generation of skinned fibres in the developing rat
      heart.
AB  - During development of the myocardium the troponin I (TNI) isoform expression is
      switched from a cAMP-insensitive, slow skeletal muscle TNI to a cAMP-sensitive,
      cardiac TNI isoform (cTNI). To study the functional consequence of alterations in
      cTNI expression in the rat heart we investigated the cAMP-controlled cTNI
      phosphorylation in comparison with alterations of functional properties of
      isolated cardiac myofibrils during the first postnatal month. cTNI was identified
      by Western blot analysis followed by a semiquantitative assessment. From the
      third to the 28th postnatal day the relative concentrations of the cardiac
      isoform of TNI increased 2.9 +/- 0.3-fold. In the same period the amount of
      phosphate incorporated into cTNI in the presence of exogenous cAMP-dependent
      protein kinase (PKA) and 32P[gamma]-ATP was increased 5.8 +/- 0.2-fold (24.2 +/-
      3.5 v 140.2 +/- 7.6 pmolP/mg protein loaded onto the gel) whereas the
      phosphorylation of C-protein was only increased 1.6 +/- 0.2-fold. Ca(2+)
      activated isometric tension generation of skinned heart fibres measured in the
      range of pCa from 6 to 4.5 was not affected by PKA at day 3. However, isometric
      tension generation of fibres prepared from 28-day-old rats was suppressed by
      incubation with PKA which was accompanied by a rightward shift in the force/pCa
      relation. Under these conditions half-maximal tension development was found at
      pCa 5.38 v 5.52 (p < 0.05) in the absence of PKA. The Ca2+ sensitivity of the
      contractile apparatus was not affected by PKA-induced phosphorylation of C
      protein. These data give direct evidence for the physiological relevance of the
      onset of cAMP-induced phosphorylation of cTNI for the Ca(2+)-activated tension
      generation in cardiac myofibrils during postnatal development.

PMID- 7815457
TI  - Reduced calcium current density in single myocytes isolated from hypertrophied
      failing guinea pig hearts.
AB  - The present study explored the possibility that an alteration in the
      transmembrane calcium current (ICa), through its ability to modulate Ca2+ release
      from the sarcoplasmic reticulum, could contribute to the depressed peak [Ca2+]i
      we previously observed in hypertrophied failing myocardium. Whole-cell patch
      clamp was used to measure ICa in single guinea pig ventricular myocytes isolated
      from hearts of normal guinea pigs and from guinea pig hearts in which hypertrophy
      and failure were induced by gradually developing left ventricular pressure
      overload subsequent to ascending aortic banding of young animals. Membrane
      capacitance (Cm) was significantly greater. and ICa, normalized for Cm, was
      significantly lower in myocytes from hypertrophied failing hearts. Myocytes from
      hypertrophied failing hearts did not differ significantly from normal myocytes in
      terms of the voltage-dependence of the activation variable (d) of ICa (except at 
      30 mV), the time course of removal of inactivation of ICa, and the time constant
      of decay of ICa. Measurement of the voltage dependence of the inactivation
      variable (f) of ICa showed that significantly more steady-state inactivation was
      present at 0, -10, and -20 mV in myocytes from hypertrophied failing hearts.
      Multiple regression analysis of all data indicated that ICa density decreased
      with increasing myocyte membrane area (as reflected by Cm) irrespective of any
      specific effects of hypertrophy and heart failure. We conclude that ICa,
      normalized for Cm, is significantly reduced in myocytes isolated from
      hypertrophied failing hearts, probably by a process associated with increased
      cell size, per se.

PMID- 7815458
TI  - Thyroid hormone enhances Ca2+ pumping activity of the cardiac sarcoplasmic
      reticulum by increasing Ca2+ ATPase and decreasing phospholamban expression.
AB  - Phospholamban is a putative suppressor of the Ca2+ ATPase of the cardiac
      sarcoplasmic reticulum. The level of mRNA encoding the Ca2+ ATPase has been shown
      to be increased, whereas the phospholamban mRNA level to be decreased in the
      ventricles obtained from hyperthyroid rabbits [Nagai R, Zarain-Herzberg A. Brandl
      CJ, Fujii J. Tada M. MacLennan DH, Alpert NR, Periasamy M. (1989) Proc Natl Acad
      Sci USA 86: 2966-2970]. The present study was designed to examine whether these
      effects of thyroid hormone on the expression of the Ca2+ ATPase and phospholamban
      are exerted directly on cardiac myocytes and whether the resultant incoordinate
      expression of these proteins alters Ca2+ pumping activity. We studied the levels
      of phospholamban and Ca2+ ATPase mRNA in primary isolated neonatal rat myocardial
      cells incubated with triiodothyronine (T3) for 3-48 h and the Ca2+ uptake
      activity of the microsomes prepared from the cells. Northern blot analysis showed
      that T3 decreased phospholamban mRNA levels to about a half of control in 24 h.
      On the other hand, Ca2+ ATPase mRNA gradually increased with time. EC50 for
      phospholamban mRNA expression was 2.5 x 10(-10) M which was approximately 10
      times higher than that for the Ca2+ ATPase. T3 increased Vmax of Ca2+ uptake with
      the significant reduction of K0.5 for Ca2+ (0.40 +/- 0.02 microM for control v
      0.31 +/- 0.02 microM for T3-treated vesicles), indicating that thyroid hormone
      stimulates Ca2+ pumping activity not only by increasing the Ca2+ ATPase but also
      decreasing phospholamban. These results suggested that phospholamban regulates
      the Ca2+ ATPase in dual modes; in short time range, by decreasing the affinity of
      the Ca2+ ATPase for Ca2+ by phosphorylation of phospholamban with cAMP-dependent
      protein kinase, and in long time range, by changing the molecular ratio between
      the two proteins through the regulation of gene expression.

PMID- 7815459
TI  - Characterization and nucleotide sequence of the cardiac alpha-myosin heavy chain
      gene from Syrian hamster.
AB  - In small mammals, the cardiac alpha-myosin heavy chain (MyHC) gene is
      predominantly expressed in the adult ventricle, while the beta-MyHC gene is
      predominantly expressed in the fetal ventricle. In order to perform comparative
      studies of these genes, we sequenced the Syrian hamster alpha-MyHC gene by
      determining a continuous 32,415 base pair (bp) sequence. It contained 39 exons
      encoding a predicted polypeptide of 1939 amino acid residues (aa) with a
      molecular weight of 223,644 Da. Sequence comparison revealed that the coding
      sequence is highly identical to that of the human alpha-MyHC gene. A marked
      feature of the Syrian hamster alpha-MyHC gene was the abundance of reiterated
      sequences within introns. Eleven B1 and four B2 retroposons were identified, a
      variety of di-, tri-, and tetra-nucleotide repeats were present, and three longer
      direct repeats were found. Some of them appear to be associated with genetic
      recombination events.

PMID- 7815460
TI  - Comparison of different iron chelators as protective agents against acute
      doxorubicin-induced cardiotoxicity.
AB  - Doxorubicin (Dox) is a widely used antineoplastic agent. Irreversible
      cardiomyopathy is a serious and dose-limiting side effect after chronic
      administration. The iron chelating bispiperazinedione ICRF-187 is currently the
      only drug which affords protection against Dox-induced cardiotoxicity. To compare
      the protective value of structurally unrelated iron chelators, isolated mice
      atria were exposed to Dox (30 microM) and either the hydroxamate desferrioxamine
      (DFO, 200 and 500 microM), EDTA (200 microM) or the hydroxypridones CP44 (200
      microM), CP51 (200 microM), and CP93 (200 microM) and ICRF-187 (200 and 500
      microM). The nitroxide TEMPO (5 mM) lacks iron chelating properties but was used
      to prevent redox cycling or iron and scavenge superoxide. All iron chelators,
      except EDTA. CP93 and CP44, were modestly protective against a Dox-induced
      decrease in contractile force. As a single agent the hydroxypridones decreased
      atrial contractile force. At a concentration of 200 microM, DFO was the most
      effective protector of the chelators tested. However, this effect disappeared
      when a concentration of 500 microM was used. This in contrast to ICRF-187 for
      which a concentration-dependent inhibition of Dox-induced decrease in contractile
      force was observed. TEMPO exerted a biphasic response consisting of a two-fold
      increase in contractile force, followed by a decrease in force and irregular
      contractions. In this model TEMPO lacked any perspective as a cardioprotectant.
      We conclude that at 200 microM. DFO was the most effective agent to afford
      protection against Dox-mediated atrial malfunction. However, at 500 microM, DFO
      was not effective whereas ICRF-187 afforded partial protection. Hydroxipyridones
      were found to be of limited value because of a negative inotropic effect on the
      isolated atria.

PMID- 7815461
TI  - Acadesine improves tolerance to ischemic injury in rat cardiac myocytes.
AB  - The ability of acadesine to modulate injury in a myocyte model of simulated
      ischemia was studied. When freshly isolated adult rat ventricular myocytes were
      subjected to 10 min of simulated ischemia and reperfusion, greater that 75% of
      myocytes developed hypercontracture and the amplitude of contraction of the
      remaining, potentially viable myocytes was markedly depressed. When cells were
      pretreated with 50 microM acadesine for 5 min and exposed to acadesine during
      simulated ischemia and during 2-10 min of reperfusion, followed by reperfusion
      with control buffer, up to 90% of myocytes maintained normal morphology and could
      be stimulated to contract. Acadesine alone had no significant effect on amplitude
      of contraction of the myocytes. Acadesine is known to alter adenosine metabolism
      and to increase coronary sinus [adenosine] in the ischemic heart. When cells were
      treated with the non-selective adenosine receptor antagonist 8
      sulfonylphenyltheophylline, the protective effect of acadesine was abolished.
      Thus, in this adult rat cardiac myocyte model of simulated ischemia, acadesine
      protects partially against ischemia/reperfusion injury. The protective effect of
      acadesine is mediated, at least in part, by an adenosine receptor-dependent
      mechanism.

PMID- 7815462
TI  - Simultaneous and separable flux of pathways for glucose and glycogen utilization
      studied by 13C-NMR.
AB  - Glucose utilization and glycogen turnover was studied by 13C-NMR in segments of
      hog carotid artery smooth muscle. After superfusion of carotid segments for 8-16
      h at 37 degrees C with C-1 labeled glucose. 13C-NMR spectra revealed substantial
      incorporation into glycogen, lactate and into resonances tentatively identified
      as glutamate at the C-2 and C-4 positions. The rate of net glycogen incorporation
      was approximately linear over 8 h in unstimulated muscle. After washing out the
      initial labeled glucose, carotids were contracted by 80 mM KCl in the presence of
      C-2 labeled glucose. During the contraction simultaneous flux of glycogenolysis
      and glycolysis was observed with production of lactate labeled at the C-2
      position (from glucose labeled at the second carbon) and with the magnitude of
      the glycogen resonance decreasing. However, no lactate labeled at the C-3
      position (derived from C-3 glycogen) was observed at the end of a prolonged
      contraction. If complete mixing of the intermediates of the two pathways
      occurred, lactate derived from both glucose and glycogen would have been
      observed. When similar experiments are performed in the presence of 5 mM NaCN to
      block oxidative metabolism, then lactate derived from glucose and from glycogen
      was clearly observed. Therefore, when oxidative metabolism was intact, the
      intermediates of glycogenolysis and glycolysis did not normally appear to fully
      mix despite simultaneous flux of the two pathways during contraction. These
      separable cytosolic pathways for carbohydrate utilization are proposed to be
      governed by a reaction-diffusion class of mechanism. Such an organization of
      cytosolic enzymes may represent a general feature of cell metabolism.

PMID- 7815463
TI  - T-type calcium current in latent pacemaker cells isolated from cat right atrium.
AB  - Whole-cell voltage clamp techniques were used to study Ca2+ currents in latent
      pacemaker cells isolated from cat right atrium. T-type (ICa,T) and L-type (ICa.L)
      Ca2+ currents were distinguished by their voltage dependence of activation, and
      sensitivity to channel blocking agents. In 2.7 mM [Ca]o, ICa,T activation
      exhibited a voltage threshold of about -50mV and maximum amplitude at -10mV,
      whereas ICa,L threshold was about -30mV and maximum amplitude was at +10mV. The
      half-maximal activation voltages of ICa,T was -31.4 +/- 0.2mV and ICa,L was -6.2
      +/- 2.0mV. Overlap of the steady-state activation-inactivation curves for ICa,T
      showed a "window" current at voltages compatible with the late phase of diastolic
      depolarization. Maximum ICa,T and ICa,L current densities were 3.3 +/- 0.4pA/pF
      and 12.5 +/- 1.3pA/pF, respectively. ICa,T current density in working atrial
      muscle cells was 0.73 +/- 0.31pA/pF. Both ICa,L and ICa,T were blocked by 2mM
      cobalt. ICa,L but not ICa,T was blocked by 1 microM nifedipine. Nickel (Ni2+; 40
      microM) inhibited ICa,T primarily at more negative voltages. In addition, Ni2+
      decreased the late phase of diastolic depolarization and significantly increased
      pacemaker cycle length. These results indicate that latent atrial pacemaker cells
      exhibit ICa,T that is significantly larger in amplitude than in working atrial
      muscle cells. ICa,T may contribute current during the late phase of diastolic
      depolarization. Because latent pacemakers exhibit a more negative maximum
      diastolic potential, ICa,T may contribute more to latent than to primary
      pacemaker activity.

PMID- 7815464
TI  - Mechanical abnormalities in the rat ischemic heart failure model which lie
      downstream to cAMP production.
AB  - OBJECTIVE: We previously showed diminished inotropic responses to isoproterenol
      in uninfarcted posterior papillary muscles of rats with anterior wall infarcts
      comprising > or = 30% of the left ventricle. We have also shown that this occurs
      in the absence of beta-receptor downregulation. Our objective was to show a
      mechanical defect in the rat infarct model which is secondary to cellular defects
      downstream to cAMP production. METHODS: Sprague-Dawley rats were infarcted via
      coronary ligation. After 3 weeks, the uninfarcted papillary muscle was placed in
      a muscle bath and exposed to increasing concentrations of dibutyryl cAMP while
      contracting isometrically at 28 degrees C. RESULTS: The large infarct group
      showed evidence of right ventricular hypertrophy which was manifested by an
      increased right ventricular mass. No differences were found in baseline
      measurements of developed tension (DT); rate of tension development (dT/dt); rate
      of relaxation (-dT/dt); time to peak tension (TPT); and relaxation time (t1/2R).
      When these muscles were stimulated with dibutyryl cAMP, the large infarct group
      had a reduced inotropic response as measured by +dT/dt and TPT. No consistent
      abnormalities were noted in relaxation. The findings are similar to those we
      noted previously with isoproterenol stimulation. CONCLUSION: The impaired
      response to beta stimulation in uninfarcted myocardium from rats with large
      myocardial infarctions is due to cellular defects which lie downstream to cAMP
      production.

PMID- 7815465
TI  - Effects of capsaicin on mechanoenergetics of excised cross-circulated canine left
      ventricle and coronary artery.
AB  - Capsaicin selectively acts on sensory nerve endings in cardiac muscles and
      coronary arterial smooth muscles. Capsaicin at high doses has cell-nonselective
      effects including both inhibition of cardiac muscle exciteability and enhancement
      of vascular smooth muscle tone. We studied whether and how intracoronary infusion
      of capsaicin affects mechanoenergetics of the excised blood-perfused canine heart
      and coronary vascular resistance. We found that capsaicin at low concentrations
      increased Emax (a contracility index) and oxygen consumption (VO2) possibly due
      to a specific action on capsaicin-sensitive sensory nerves in left ventricular
      muscles, though in a small number of hearts (3/10). This result coincides with
      the reported histochemical observations that the distribution of capsaicin
      sensitive sensory nerves in the canine left ventricle is not dense. Capsaicin at
      high doses dose-dependently decreased Emax and proportionally decreased coronary
      flow. It also lowered the linear VO2-PVA (pressure-volume area; total mechanical
      energy) relationship without a change in the slope, decreasing unloaded VO2 (VO2
      intercept of the VO2-PVA relation). These effects of high-dose capsaicin seem to
      be direct negative inotropic action on cardiac muscles associated with
      enhancement of coronary arterial smooth muscle tone, since these effects were not
      desensitized. No morphological changes of myocardial cells or mitochondria were
      detected. Therefore, the negative inotropic action is not due to the toxic effect
      of capsaicin.

PMID- 7815466
TI  - Identification of a mutation near a functional site of the beta cardiac myosin
      heavy chain gene in a family with hypertrophic cardiomyopathy.
AB  - Several mutations within the gene coding for the cardiac beta myosin heavy chain
      (designed MYH7) have been shown to be responsible for Familial Hypertrophic
      Cardiomyopathy (FHC) in several families, and evidence of genetic heterogeneity
      has been reported. To investigate the MYH7 gene as the cause of the disease in a
      small family with FHC, inheritance of the disease and chromosome 14 q11-q12
      markers haplotype were studied, exons coding for the head domain of the cardiac
      beta myosin heavy chain (beta MHC) were analysed for mutations by MDE gel
      electrophoresis, and sequenced. We report a mutation within exon eight of the
      MYH7 gene at a very conserved amino acid at position 232, which results in the
      conversion of an asparagine to serine. This residue Asn-232 is located in a MHC
      area that has been recently identified as a critical site for ATPase activity.
      According to recent results on the three-dimensional structure of the myosin head
      or subfragment-1 (S1), Asn-232 is located in an alpha-helix which forms part of
      the nucleotide binding pocket. Although this mutation affects an active site, it
      seems to be associated with a favourable prognosis and a weak penetrance in this
      family.

PMID- 7815467
TI  - The trolox analog, U-78517F, attenuates hypoxic injury in isolated cardiac
      myocytes.
AB  - Neonatal rat cardiac myocytes were subjected to 5 h of hypoxia (PO2 < 5 mmHg) in
      glucose-free, modified Tyrodes solution. Prior to hypoxic exposure, cells were
      pretreated for 90 min with media alone or containing the trolox analog, U-78517F,
      at 0.3, 1, or 3 microM. Hypoxic injury was characterized by a significant loss of
      sarcolemmal integrity [76 +/- 12% of the total cell fluorescence (mean +/- S.E.,
      n = 14 cultures)] quantified by nuclear staining with the membrane-impermeant
      fluorophore propidium iodide. In addition, hypoxia also induced significant
      decreases in the intracellular content of creatine kinase (43 +/- 7%, n = 12),
      lactate dehydrogenase (25 +/- 5%, n = 8), adenosine 5'-triphosphate (49 +/- 12%,
      n = 6), and sulfhydryls (34 +/- 4%, n = 6). Sarcolemmal integrity was
      significantly preserved by pretreatment with 1 microM and 3 microM U-78517F which
      reduced propidium iodide staining below the hypoxic control value by 51 +/- 9% (n
      = 12) and 75 +/- 4% (n = 14, P < 0.01 v hypoxic control), respectively. Similar
      results were obtained in cells pretreated with alpha-tocopherol suggesting that
      these two compounds are equipotent at preserving the sarcolemmal integrity of
      cardiac myocytes exposed to hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7815468
TI  - VASE exon expression alters NCAM-mediated cell-cell interactions.
AB  - The neural cell adhesion molecule (NCAM) is found on cells as several related
      polypeptides formed by alternative splicing of the single NCAM gene. The
      alternatively spliced 30-bp VASE exon in the fourth immunoglobulin-like domain is
      the structural variation nearest those portions of the polypeptide proposed to
      mediate cell-cell adhesion. To test the ability of distinct forms of the NCAM
      molecules to mediate cell adhesion, L cells were transfected with expression
      vectors encoding rat 140 kD NCAM +/- the VASE exon. L cell lines which expressed
      these polypeptides were isolated and tested for self-aggregation in a low shear,
      rapid aggregation assay. Increased cellular aggregation of the transfectants was
      observed to be a function of the NCAM molecule expressed. These transfected cells
      showed segregation in a long term co-aggregation assay: cells expressing NCAM-
      VASE formed aggregates which tended to exclude cells expressing NCAM+VASE and
      vice versa. These results provide direct evidence that this small difference in
      NCAM structure is sufficient to allow segregation of cells.

PMID- 7815469
TI  - Coexpression of alpha and gamma enolase genes in neurons of adult rat brain.
AB  - Enolase (EC 4.2.1.11) is a glycolytic enzyme active as a dimer. In adult brain
      extracts, three forms, alpha alpha, alpha gamma and gamma gamma, have been
      described, with the alpha gamma hybrid accounting for 30% of total enolase
      activity (Fletcher et al., Dev Biol 65:462-475, 1978; Lucas et al., Dev Neurosci
      10:91-98, 1988). Previous biochemical studies strongly suggest that this hybrid
      is not generated artefactually during the extraction procedures (Keller et al., J
      Neurochem 36:1389-1397, 1981; Shimizu et al., BBA 748:278-284, 1983).
      Immunocytological observations have demonstrated the cell specific localization
      of the alpha subunit in astrocytes and of the gamma subunit in neurons at the
      adult stage, but failed to identify a cell type containing both the alpha and
      gamma subunits necessary for the formation of the alpha gamma hybrid isoform
      (Ghandour et al., Exp Brain Res 41:271-279, 1981; Vinores et al., J Histochem
      Cytochem 32:1295-1302, 1984; Iwanaga et al., Arch Histol Cytol [Suppl] 52:13-24,
      1989). We sought to approach this question by performing in situ hybridization
      studies in order to visualize the alpha and gamma mRNAs. In agreement with the
      immunocytological reports, we observe a specific accumulation of the gamma
      enolase transcripts in neurons and a high accumulation of alpha enolase
      transcripts in some glial cells such as the ependymocytes lining the ventricles.
      Our observations, following hybridization with 35S labeled oligonucleotide
      specific probes on adjacent thin sections, demonstrate for the first time that
      transcription of both alpha and gamma enolase genes occurs in many neurons of
      different brain regions. These results render highly probable the formation of
      the alpha gamma hybrid in mature neurons. Furthermore, we observe a differential
      expression of the genes encoding the alpha and gamma enolase subunits in various
      neuronal populations of the brain. The implications of these observations are
      discussed.

PMID- 7815470
TI  - Amphiphilic properties of molecular forms of acetylcholinesterase in normal and
      dystrophic muscle.
AB  - Acetylcholinesterase (AChE) molecular forms were studied in normal (NM) and in
      dystrophic (DM) 129B6F1/J mouse muscle. Successive extractions of the tissue with
      saline and saline-Triton X-100 buffers yielded two soluble fractions, S1 and S2.
      Forty percent of the AChE in NM was measured in S1 and 60% in S2, and 65% and
      35%, respectively, in extracts from DM. A12, A8, G4, G2, and G1 forms of AChE
      were found in S1 and S2 from NM and DM. A similar content of asymmetric molecules
      was noticed between NM and DM. G4 AChE was a minor species in DM, and G1 and G2
      AChE were more abundant in DM than in NM. The amphiphilic properties of the
      several molecules were assessed by Triton X-114 phase-partitioning and
      hydrophobic chromatography. Thirty and 70% of the enzyme in a mixture of S1 and
      S2 partitioned in the detergent-rich and in the detergent-poor phases,
      respectively, whether the extracts were obtained from NM or DM. Asymmetric and G4
      AChE predominated in the aqueous phase and G1 and G2 in the detergent phase. Ten
      and 25% of the enzyme in S1 from NM or DM, respectively, was adsorbed to the
      phenyl-agarose. Elution of the retained enzyme followed by sedimentation analysis
      revealed that a certain amount of asymmetric and most of the G1 and G2 forms were
      associated with the matrix. The content of amphiphilic asymmetric and light
      globular forms was notably higher in DM than in NM. The results suggest that
      dystrophic muscle produces a specific pattern of molecular forms of AChE.

PMID- 7815471
TI  - Developmental dynamics of Purkinje cells and dendritic spines in rat cerebellar
      cortex.
AB  - Quantitative morphological changes of the developing Purkinje cells were studied
      from 6 to 90 postnatal (PN) days in the IVth lobule of vermis in the cerebellum
      of rats. The soma size (mean diameter) of Purkinje cells increased rapidly
      between 6 PN (on average 10 microns) and 18 PN (about 17 microns) days; it did
      not change between 18 and 25 PN days, but increased moderately again between 25
      and 48 PN days (22-23 microns) and stabilized on the same value. In contrast, the
      number of Purkinje cells/100 microns (the "linear density") decreased rapidly
      from 6 to 18 PN days. The molecular layer area belonging to 1 Purkinje cell
      increased rapidly from 6 to 25 PN days (from about 370 to 6,200 microns 2) and
      less rapidly between PN days 30 to 48 (up to 9,300 microns 2), followed by a
      moderate decrease at PN day 90 (about 6,600 microns 2). The volume belonging to 1
      Purkinje cell dendritic arbor was about 5,500 microns 3 at PN day 6, 93,000
      microns 3 at PN day 25, and 100,000 microns 3 at PN day 90. The numerical density
      of dendritic spines in the molecular layer showed a biphasic curve: a rapid
      increase from PN days 6 to 21 followed by a significant but short decrease at PN
      day 25, moderate rise from PN days 25 to 48, and a subsequent decline between PN
      days 48 and 90. The number of spines belonging to 1 Purkinje cell showed two
      developmental "peaks": the first peak at 21 PN days was moderate (5.6 x 10(4)
      spines/Purkinje cell) while the second maximum at 48 PN days was more significant
      (1.2 x 10(5) spines/Purkinje cell), which then declined to 6.3 x 10(4)
      spines/Purkinje cell at PN day 90. It is suggested that the temporary
      overproduction and the following decline in the number of Purkinje dendritic
      spines during the development of the cerebellar cortex may be the morphological
      indicator of the dynamics of synaptogenetic and of synaptic stabilization
      processes.

PMID- 7815472
TI  - A new oligodendrocyte specific plasma membrane surface protein identified by a
      monoclonal antibody produced in vitro.
AB  - This paper describes a novel monoclonal antibody (C1G5F2) derived from mice
      splenocytes immunized in vitro with a wheat germ agglutinin glycoprotein fraction
      isolated from bovine central nervous system (CNS) myelin. Immunohistochemical
      reactions with C1G5F2 were investigated on rat brain sections during the active
      period of myelination. From day 10 to 13 postnatally, no stained structures were
      observed throughout the whole brain. The first immunolabeled myelin fibers were
      detected within the pons at day 14, and the white matter areas in the cerebrum
      started to be stained some days later. White matter areas of the cerebellum were
      clearly immunopositive after the third week. There was a strong positive signal
      on myelin fibers in the cerebrum at day 30. By contrast, no immunolabeled cell
      bodies of oligodendrocytes were observed throughout the brain. The other neural
      cell types were also not labeled. This C1G5F2 monoclonal antibody bound mainly to
      the extracytosolic membrane surface of the processes of live cultured
      oligodendrocytes derived from newborn rat brain but was unreactive with live or
      fixed astrocytes and neurons maintained in culture. No immunostaining was
      detected in the peripheral nervous system or in the spleen, liver, or pancreas.
      The C1G5F2 epitope containing antigen may therefore be considered as a CNS
      myelin/oligodendrocyte specific molecule. Sodium deoxycholate-Tween 20 extracts
      of secondary oligodendrocyte cultures, biotinylated with biotin hydrazide, were
      used to attempt the purification of the antigen with C1G5F2 IgMs linked to
      antimouse IgM agarose. A main broad biotinylated protein band of 54-58 kDa
      molecular mass was noted. In a second approach, the antigen was immunopurified
      from cultured oligodendrocytes as an immune complex using biotinylated C1G5F2
      IgMs. A distinct protein doublet of 53-56 kDa was also observed. It is postulated
      that this antigen may play an essential role in myelin formation and could be a
      possible target in diseases restricted to CNS myelin.

PMID- 7815473
TI  - Expression of growth-associated protein-43 kD in Schwann cells is regulated by
      axon-Schwann cell interactions and cAMP.
AB  - We have examined the regulation of growth-associated protein 43 kD (GAP-43) in
      rat Schwann cells. In unlesioned adult nerves, GAP-43-immunoreactivity was
      restricted to non-myelinating Schwann cells and unmyelinated axons. When adult
      nerves were transected to cause permanent axotomy, previously myelinating Schwann
      cells expressed progressively more GAP-43-immunoreactivity over 3 weeks, and GAP
      43 mRNA levels increased over a similar time course. The peak level of GAP-43
      mRNA occurred at least 2 weeks later than that of nerve growth factor receptor,
      another marker of denervated Schwann cells. In contrast, after nerve-crush, which
      allows axonal regeneration, many fewer Schwann cells had GAP-43-immunoreactivity,
      and the amount of GAP-43 mRNA was markedly lower than in transected nerves.
      Forskolin, a drug that activates adenylate cyclase and mimics many effects of
      axon-Schwann cell interactions, markedly reduced GAP-43-immunoreactivity and mRNA
      expression in cultured Schwann cells, whereas interleukin-1 had no effect. These
      data demonstrate that axon-Schwann cell interactions inhibit the expression of
      GAP-43 in Schwann cells and that this effect is mimicked by forskolin.

PMID- 7815474
TI  - Fibroblast growth factor-induced increases in calcium currents in the PC12
      pheochromocytoma cell line are tyrosine phosphorylation dependent.
AB  - The PC12 rat pheochromocytoma cell line is widely used to study neuronal
      differentiation by growth factors. In response to nerve growth factor (NGF) and
      basic fibroblast growth factor (bFGF), PC12 cells differentiate into sympathetic
      like neurons and become electrically excitable. Using whole cell patch-clamp
      recording, with barium as a charge carrier, we looked at the effects of bFGF on
      calcium channel expression as reflected by changes in barium current amplitudes
      normalized to cell membrane area. Similar to the effect reported for NGF, we show
      that 7 day treatment with bFGF increased the barium current approximately 4-fold.
      The largest contributor to the increase in barium current with bFGF treatment is
      a 6-fold increase in the high threshold voltage activated omega-conotoxin
      sensitive barium current. Smaller increases in current produced by bFGF treatment
      of PC12 cells are observed for the dihydropyridine sensitive and
      dihydropyridine/conotoxin insensitive currents. The bFGF-induced increases in
      barium currents are dependent on tyrosine phosphorylation, since the effects of
      bFGF are blocked by genistein, a tyrosine kinase inhibitor. This system will
      ultimately be useful in understanding the signaling pathways that control calcium
      channel expression in response to growth factors.

PMID- 7815475
TI  - p75 nerve growth factor receptor modulates p140trkA kinase activity, but not
      ligand internalization, in PC12 cells.
AB  - The biological activity of nerve growth factor (NGF) has been shown to be
      mediated by the p140trkA receptor tyrosine kinase, while the role of the p75 NGF
      receptor (p75NGFR) is still unresolved. Here we have investigated the relative
      contribution of p140trkA and p75NGFR to early consequences of NGF binding: ligand
      internalization, p140trkA autophosphorylation, and tyrosine phosphorylation of
      Shc, phospholipase C gamma-1 (PLC gamma-1), and extracellular signal-regulated
      kinases (ERKs). It was found that NGF internalization was neither prevented by
      blocking p140trkA activity using the protein kinase inhibitors
      methylthioadenosine, staurosporine, and K-252a, nor by inhibiting NGF binding to
      p75NGFR with antibodies. However, when NGF binding to p140trkA was reduced by the
      use of a synthetic peptide corresponding to amino acids 36-53 of human p140trkA,
      internalization of NGF was decreased. Thus, at least in PC12 cells,
      internalization appears to require binding of NGF to p140trkA, but occurs
      irrespective of p140trkA kinase activity and ligand occupancy of p75NGFR. The NGF
      triple mutant Lys-32/Lys-34/Glu-35 to Ala, which has been demonstrated to bind to
      p140trkA, but not to p75NGFR, induced tyrosine phosphorylation more rapidly than
      wild-type NGF. Likewise, NGF-induced tyrosine phosphorylation was accelerated
      when NGF binding to p75NGFR was prevented with REX-IgG. These findings indicate
      that NGF bindign by p75NGFR may modulate NGF-induced p140trkA kinase activity.

PMID- 7815476
TI  - Genetic analysis of human immunodeficiency virus type 1 envelope V3 region
      isolates from mothers and infants after perinatal transmission.
AB  - The human immunodeficiency virus type 1 (HIV-1) sequences from variable region 3
      (V3) of the envelope gene were analyzed from seven infected mother-infant pairs
      following perinatal transmission. The V3 region sequences directly derived from
      the DNA of the uncultured peripheral blood mononuclear cells from infected
      mothers displayed a heterogeneous population. In contrast, the infants' sequences
      were less diverse than those of their mothers. In addition, the sequences from
      the younger infants' peripheral blood mononuclear cell DNA were more homogeneous
      than the older infants' sequences. All infants' sequences were different but
      displayed patterns similar to those seen in their mothers. In the mother-infant
      pair sequences analyzed, a minor genotype or subtype found in the mothers
      predominated in their infants. The conserved N-linked glycosylation site proximal
      to the first cysteine of the V3 loop was absent only in one infant's sequence set
      and in some variants of two other infants' sequences. Furthermore, the HIV-1
      sequences of the epidemiologically linked mother-infant pairs were closer than
      the sequences of epidemiologically unlinked individuals, suggesting that the
      sequence comparison of mother-infant pairs done in order to identify genetic
      variants transmitted from mother to infant could be performed even in older
      infants. There was no evidence for transmission of a major genotype or multiple
      genotypes from mother to infant. In conclusion, a minor genotype of maternal
      virus is transmitted to the infants, and this finding could be useful in
      developing strategies to prevent maternal transmission of HIV-1 by means of
      perinatal interventions.

PMID- 7815477
TI  - Proteinase-resistant factors in human erythrocyte membranes mediate CD4-dependent
      fusion with cells expressing human immunodeficiency virus type 1 envelope
      glycoproteins.
AB  - Murine CD4+ cells are resistant to human immunodeficiency virus type 1 (HIV-1)
      entry and to fusion with cells expressing HIV-1 envelope glycoproteins (Env). The
      role of human-specific factors in Env/CD4-mediated fusion is shown by the ability
      of transient cell hybrids formed between CD4+ murine cells and human HeLa cells
      to fuse with Env+ cells. Fusion events were observed when other human cells,
      including erythrocytes, were substituted for HeLa cells in the hybrids.
      Experiments with erythrocyte ghosts showed that the factors allowing Env/CD4
      mediated fusion are located in the plasma membrane. These factors were fully
      active after extensive digestion of erythrocytes with proteinase K or pronase.
      Nonprotein components of human plasma membranes, possibly glycolipids, could
      therefore be required for Env/CD4-mediated fusion and virus entry.

PMID- 7815478
TI  - Importance of cysteines in the LDLR-related domain of the subgroup A avian
      leukosis and sarcoma virus receptor for viral entry.
AB  - The extracellular domain of the subgroup A avian sarcoma and leukemia virus (ALSV
      A) receptor contains a region that is related in sequence to the ligand-binding
      motifs of the low-density lipoprotein receptor (LDLR). This domain contains six
      cysteines that are highly conserved between different members of the LDLR protein
      superfamily, and these residues are presumed to participate in intrachain
      disulfide bonds. To assess the importance of each cysteine in the ALSV-A
      receptor, individual or multiple cysteines were mutated to alanines and the
      altered receptors were tested for the ability to confer susceptibility to viral
      infection. Receptors bearing single mutations allowed subgroup A viral entry,
      albeit at less than wild-type levels. Receptors containing two or three
      substitutions were completely inactive if one of the changed residues was Cys-35
      or Cys-50. Of the altered receptors tested, the only exception to this rule was a
      functional receptor which lacked both Cys-35 and Cys-50, an activity that was
      dependent on the presence of other cysteines in this protein. Most interestingly,
      a receptor containing both Cys-35 and Cys-50 but lacking the other four cysteines
      was completely functional. These results demonstrate the importance of Cys-35 and
      Cys-50 for viral entry mediated by the ALSV-A receptor and show that in the
      presence of these two residues, all of the other cysteines in this protein can be
      removed without loss of this function.

PMID- 7815479
TI  - Phosphorylation and nuclear localization of the hepatitis B virus core protein:
      significance of serine in the three repeated SPRRR motifs.
AB  - Hepatitis B virus core protein (antigen) is an important serologic marker of
      hepatitis B virus infection. This protein is found in the cytoplasm or the
      nuclei, or both, of infected hepatocytes. A nuclear localization signal has
      previously been identified in the core protein sequence. This signal overlaps
      three repeated SPRRR motifs. In this report, we demonstrate that substitution of
      all of the serine residues in these three SPRRR motifs with alanine can prevent
      almost entirely the phosphorylation of the core protein in Huh-7 hepatoma cells,
      enhance nuclear localization of the core protein in both Huh-7 and nonhepatic
      cells, and abolish cell cycle regulation of nuclear localization of the core
      protein. Since the three core protein mutants which retained only one serine
      residue of each of the three SPRRR motifs could be phosphorylated to similar
      degrees, these three serine residues likely could serve as the acceptor sites for
      phosphorylation with equal efficiency. These results, together with the
      observation that the three SPRRR motifs overlap the nuclear localization signal
      of the core protein, raise the possibility that nuclear localization of the core
      protein is negatively regulated by phosphorylation of the serine residues in the
      SPRRR motifs.

PMID- 7815480
TI  - Translational inhibition by a human cytomegalovirus upstream open reading frame
      despite inefficient utilization of its AUG codon.
AB  - The second of three short upstream open reading frames (uORF2) in the transcript
      leader of the human cytomegalovirus gp48 (gpUL4) virion glycoprotein gene
      inhibits downstream translation approximately 10-fold. Remarkably, this
      inhibition depends on the amino acid coding information of uORF2. In the current
      studies we demonstrate that expression of the cistron downstream from uORF2
      depends on ribosomes bypassing the uORF2 AUG codon (AUG2) by a leaky scanning
      mechanism. Replacing the nucleotides surrounding the wild-type AUG2 codon with
      those optimal for translation initiation reduces downstream translation
      approximately 10-fold. Analyses of mutants in which uORF2 either overlaps or is
      in frame with the downstream reading frame reveal that the initiation frequency
      at the wild-type AUG2 codon is surprisingly low; rather, the majority of
      ribosomal subunits bypass the wild-type AUG2 codon because of its suboptimal
      context. We propose a model to explain this unprecedented example of a
      paradoxically strong inhibitory effect of an upstream ORF despite inefficient
      utilization of its initiation codon.

PMID- 7815481
TI  - Recombinant mink cell focus-inducing virus and long terminal repeat alterations
      accompany the increased leukemogenicity of the Mo+PyF101 variant of Moloney
      murine leukemia virus after intraperitoneal inoculation.
AB  - We recently showed that different routes of inoculation affect the
      leukemogenicity of the Mo+PyF101 variant of Moloney murine leukemia virus (M
      MuLV). Intraperitoneal (i.p.) inoculation of neonatal mice with Mo+PyF101 M-MuLV
      greatly enhanced its leukemogenicity compared with subcutaneous (s.c.)
      inoculation. We previously also suggested that the leukemogenicity defect of
      Mo+PyF101 M-MuLV when inoculated s.c. may result from the inability of this virus
      to form env gene recombinant (mink cell focus-inducing [MCF]) virus. In this
      study, virus present in end-stage tumors and in preleukemic animals inoculated
      i.p. by Mo+PyF101 M-MuLV was characterized. In contrast to s.c. inoculation, all
      tumors from i.p.-inoculated mice contained high levels of recombinant MCF virus.
      Furthermore, Southern blot analyses demonstrated that the majority of the tumors
      contained altered Mo+PyF101 M-MuLV long terminal repeats. The U3 regions from
      several tumors with altered long terminal repeats were cloned by PCR
      amplification. Sequence analyses indicated that the M-MuLV 75-bp tandem repeat in
      the enhancer region was triplicated. This amplification was also previously
      observed in mice infected s.c. with a pseudotypic mixture of Mo+PyF101 M-MuLV and
      Mo+PyF101 MCF virus. The enhancer triplication was an early event, and it
      occurred within 2 weeks postinfection. Recombinant MCF viruses were not detected
      by Southern blot analyses until 4 weeks postinfection. Thus, the M-MuLV enhancer
      triplication event was initially important for efficient propagation of ecotropic
      Mo+PyF101 M-MuLV. The increased leukemogenicity following i.p. inoculation could
      be explained if the triplication enhances Mo+PyF101 M-MuLV replication in the
      bone marrow and bone marrow infection is required for recombinant MCF virus
      formation.

PMID- 7815482
TI  - Intracellular interference of tick-borne flavivirus infection by using a single
      chain antibody fragment delivered by recombinant Sindbis virus.
AB  - A single-chain antibody fragment that identifies a neutralizing epitope on the
      envelope protein of louping ill and some other tick-borne flaviviruses was
      previously expressed in soluble form from bacteria and shown to be functionally
      active in vitro. To see whether or not the single-chain antibody could bind and
      inactivate infectious virus in vivo, we have used recombinant Sindbis virus as a
      delivery vehicle for intracellular expression of the antibody fragment. The
      variable genes and interchain linker encoding the single-chain antibody were
      cloned into a double subgenomic Sindbis virus expression vector to generate
      recombinant Sindbis virus. Infection with this recombinant Sindbis virus provided
      high-level cytoplasmic expression of the antibody fragment in mammalian cells. We
      demonstrate (i) that the antibody fragment was antigen binding and (ii) that
      louping ill virus infectivity was significantly reduced in the presence of
      intracellular antibody expressed by the superinfecting recombinant Sindbis virus.

PMID- 7815483
TI  - Epstein-Barr virus latent messages with shuffled leader exons: remnants of
      circumgenomic transcription?
AB  - The EBNA transcription unit which is active in Epstein-Barr virus-immortalized
      latently infected B lymphocytes covers approximately 60% of the 172-kb genome.
      Since the genome exists as a circular double-stranded DNA molecule in latently
      infected cells, it is conceivable that complete copies are made during
      transcription. Rather than attempt to detect gigantic RNA molecules directly, we
      used RNA-PCR to detect incorporation of leader exons into mRNA in a shuffled
      order. The downstream U leader exon was detected spliced upstream of the internal
      repeat leader exons W1 and W2 in the polyadenylated RNA fraction of spontaneous
      lymphoblastoid cell lines, restricted phenotype BL cell lines Wanyanyi and
      Wewak2, and in B95-8, Raji, and Akata cells. Quantitative competitive RNA-PCR
      showed that the ratio of U exon-containing EBNA1 messages to U exon-shuffled
      leader messages was approximately 10:1, with large variation from cell line to
      cell line, and was not affected by induction of the lytic cycle in B95-8, Raji,
      or Akata cells. Messages with shuffled exons contained only the C2W1 alternative
      splice, which does not produce an initiator AUG methionine codon for EBNA4 gene
      expression. The results provide evidence for long-range exon skipping and imply
      that genome-length transcripts may occur and participate in viral gene expression
      in latency.

PMID- 7815484
TI  - Virus-induced immunosuppression: immune system-mediated destruction of virus
      infected dendritic cells results in generalized immune suppression.
AB  - Despite the clinical importance of virus-induced immunosuppression, how virus
      infection may lead to a generalized suppression of the host immune response is
      poorly understood. To elucidate the principles involved, we analyzed the
      mechanism by which a lymphocytic choriomeningitis virus (LCMV) variant produces a
      generalized immune suppression in its natural host, the mouse. Whereas adult mice
      inoculated intravenously with LCMV Armstrong rapidly clear the infection and
      remain immunocompetent, inoculation with the Armstrong-derived LCMV variant clone
      13, which differs from its parent virus at only two amino acid positions, by
      contrast results in persistent infection and a generalized deficit in
      responsiveness to subsequent immune challenge. Here we show that the immune
      suppression induced by LCMV clone 13 is associated with a CD8-dependent loss of
      interdigitating dendritic cells from periarteriolar lymphoid sheaths in the
      spleen and, functionally, with a deficit in the ability of splenocytes from
      infected mice to stimulate the proliferation of naive T cells in a primary mixed
      lymphocyte reaction. Dendritic cells are not depleted in immunocompetent
      Armstrong-infected mice. LCMV Armstrong and clone 13 exhibit differences in their
      tropism within the spleen, with clone 13 causing a higher level of infection of
      antigen-presenting cells in the white pulp, including periarterial
      interdigitating dendritic cells, than Armstrong, thereby rendering these cells
      targets for destruction by the antiviral CD8+ cytotoxic T-lymphocyte response
      which is induced at early times following infection with either virus. Our
      findings illustrate the key role that virus tropism may play in determining
      pathogenicity and, further, document a mechanism for virus-induced
      immunosuppression which may contribute to the clinically important immune
      suppression associated with many virus infections, including human
      immunodeficiency virus type 1.

PMID- 7815485
TI  - Nuclear targeting of the tegument protein pp65 (UL83) of human cytomegalovirus:
      an unusual bipartite nuclear localization signal functions with other portions of
      the protein to mediate its efficient nuclear transport.
AB  - Large amounts of pp65 (UL83) of human cytomegalovirus are translocated to the
      cell nucleus during the first minutes after uptake of the tegument protein from
      infecting viral particles. Two stretches of basic amino acids which resembled
      nuclear localization signals (NLS) of both the simian virus 40 type and the
      bipartite type were found in the primary structure of pp65. Deletion of these
      sequences significantly impaired nuclear localization of the truncated proteins
      after transient expression. The results indicated that both elements contributed
      to the nuclear localization of the protein. When fused to the bacterial beta
      galactosidase, only one of the two basic elements was sufficient to mediate
      nuclear translocation. This element consisted of two clusters of basic amino
      acids (boxes C and D), which were separated by a short spacer sequence. In
      contrast to other bipartite NLS of animal cells, both basic boxes C and D
      functioned independently in nuclear transport, thus resembling simian virus 40
      type NLS. Yet, complete translocation of beta-galactosidase was only found in the
      bipartite configuration. When both boxes C and D were fused, thereby deleting the
      intervening sequences, the nuclear transport of beta-galactosidase was reduced to
      levels seen with constructs in which only one of the boxes was present.
      Appropriate spacing, therefore, was important but not absolutely required. This
      was in contrast with results for other bipartite NLS, in which spacer deletions
      led to complete cytoplasmic retention. The presented results demonstrate that
      efficient nuclear transport of pp65 is mediated by one dominant NLS and
      additional targeting sequences. The major NLS of pp65 is an unusual signal
      sequence composed of two weak NLS which function together as one strong bipartite
      nuclear targeting signal.

PMID- 7815486
TI  - The dimerization/packaging sequence is dispensable for both the formation of high
      molecular-weight RNA complexes within retroviral particles and the synthesis of
      proviruses of normal structure.
AB  - Retroviral particles contain a dimer of two genomic RNA molecules, linked by
      noncovalent intermolecular bonds. Studies by electron microscopy of viral RNA
      extracted from virions as well as in vitro studies have implicated a sequence,
      designated the dimer linkage sequence (DLS), in the dimerization process. The DLS
      has been localized within a short region encompassing the psi packaging sequence,
      between nucleotides 212 and 563 for the Moloney murine leukemia retrovirus
      (MoMLV) RNA. In this report, we show that viral RNAs lacking both the DLS and psi
      packaging sequences--and even an RNA lacking the first 6,537 nucleotides of MoMLV
      -can assemble within retroviral particles as high-molecular-weight, slow
      migrating, heat-sensitive complexes closely related to those observed for wild
      type viral RNAs. Furthermore, we show that proviruses of normal structure are
      generated upon infection of test cells with retroviral particles which contain
      the DLS/psi-deleted viral RNAs. These observations demonstrate that the DLS and
      psi packaging sequences are not essential in cis to form a functional RNA complex
      for reverse transcription and integration.

PMID- 7815487
TI  - Rhinovirus-mediated endosomal release of transfection complexes.
AB  - Endocytosis is an efficient method for transfer of genes into mammalian cells.
      Incorporation of adenovirus particles into gene transfer complexes greatly
      enhances gene delivery, probably by the release of endocytosed DNA into the
      cytoplasm. We report here that two different serotypes of human rhinovirus (HRV),
      HRV2 and HRV14, are also able to enhance receptor-mediated gene transfer. The
      effect of several compounds known to inhibit viral infection on HRV2- and HRV14
      enhanced transfection was examined. WIN I(s) and WIN IV, two compounds which
      inhibit viral uncoating, had different effects on HRV2- and HRV14-enhanced gene
      transfer to NIH 3T3 cells. While HRV14-enhanced gene transfer was severely
      reduced in the presence of these compounds, virtually no effects were observed
      when HRV2 was used. The use of antiviral compounds thus allowed transfection of
      human cells, which are normally lysed rapidly upon infection with HRV. Viral
      activity could be mimicked by using a peptide derived from the N terminus of VP1
      of HRV2. This peptide possesses pH-dependent membrane-disrupting activity and
      enhances gene transfer to NIH 3T3 and HeLa cells.

PMID- 7815488
TI  - Efficient in vivo and in vitro assembly of retroviral capsids from Gag precursor
      proteins expressed in bacteria.
AB  - The capsid precursor protein (Gag) of Mason-Pfizer monkey virus, the prototype
      type D retrovirus, has been expressed to high levels in bacteria under the
      control of the phage T7 promoter. Electron microscopic studies of induced cells
      revealed the assembly of capsid-like structures within inclusion bodies that
      formed at the poles of the cells 6 h after induction with isopropyl-beta-D
      thiogalactopyranoside (IPTG). The inclusion bodies and enclosed capsid-like
      structures were solubilized completely in 8 M urea, but following renaturation,
      we observed assembly in vitro of capsid-like structures that demonstrated
      apparent icosahedral symmetry. These results demonstrate for the first time that
      retroviral capsid precursors have the propensity to self-assemble in vitro and
      point to new approaches for the analysis of retroviral assembly and structure.

PMID- 7815489
TI  - Influenza type A virus neuraminidase does not play a role in viral entry,
      replication, assembly, or budding.
AB  - We have used a neuraminidase-deficient influenza virus, NWS-Mvi, which was
      selected by supplying bacterial neuraminidase in the medium (C. Liu and G. M.
      Air, Virology 194:403-407, 1993), to define the role of neuraminidase in
      influenza virus replication. Electron microscopy showed that virions of the NWS
      Mvi mutant assembled normally and formed large aggregates associated with cell
      surfaces. The NWS-Mvi virus grown in the absence of neuraminidase was able to
      carry out a second round of replication in MDCK cells without added
      neuraminidase, indicating that the virus particles contained in these aggregates
      were infectious. Aggregates of virus were also found in cytoplasmic vacuoles.
      When virus-infected cells were incubated in the presence of ferritin, such
      aggregates were found to be labeled with ferritin, indicating that they are
      derived from uptake at the cell surface. When the neuraminidase-deficient virus
      was administered intranasally to C57BL/6 mice, low titers of virus were recovered
      from the lungs and major histocompatibility complex class I-restricted cytotoxic
      T cells were generated: evidence that cells were infected in vivo. In C57BL/6
      nu/nu mice, the low level of virus persisted for at least 28 days but never
      increased. These results suggest that neuraminidase is not required for influenza
      virus entry, replication, or assembly in cell culture or in mice.

PMID- 7815490
TI  - Hepatitis B virus X protein interacts with a probable cellular DNA repair
      protein.
AB  - The mechanism of action of hepatitis B virus (HBV) X protein in transcriptional
      transactivation and in tumorigenesis remains obscure. We have used the yeast two
      hybrid system to identify a cellular protein that can interact with HBV X
      protein. This protein, designated X-associated protein 1 (XAP-1), is a human
      homolog of the UV-damaged DNA-binding protein (UV-DDB) recovered from a monkey
      cell cDNA library. UV-DDB is presumed to be involved in DNA repair. The
      interaction between X protein and XAP-1 protein was verified by
      immunoprecipitation of yeast cell lysates expressing both proteins and by in
      vitro mixing with X protein expressed as a glutathione S-transferase fusion
      protein and XAP-1 protein either in HeLa cell extracts or synthesized by in vitro
      translation. We speculate that the interaction of X protein with a DNA repair
      protein may recruit cellular proteins to repair the partially double-stranded HBV
      genome or may modify cellular transcription processes. An effect on the cellular
      DNA repair system may explain a cofactor role for HBV in liver cancer
      development.

PMID- 7815491
TI  - Essential role of the Vp2 and Vp3 DNA-binding domain in simian virus 40
      morphogenesis.
AB  - Both a DNA-binding domain and a Vp1 interactive determinant have been mapped to
      the carboxy-terminal 40 residues of the simian virus 40 (SV40) minor capsid
      proteins, Vp2 and Vp3 (Vp2/3), with the last 13 residues being necessary for
      these activities. The role of this DNA-binding domain in SV40 morphogenesis and
      the ability to separate these two signals were investigated by mutagenesis and
      assessment of the activity and viability of the mutants. The carboxy-terminal 40
      residues of Vp2/3 were expressed as a polyhistidine fusion protein, and five
      basic residues at the extreme carboxy terminus (Vp3 residues K226, R227, R228,
      R230, and R233) were mutagenized. The wild-type fusion protein bound DNA with a
      Kd of 3 x 10(-8) identical to that of the full-length Vp3. Mutant proteins
      containing either one to three or four amino acid substitutions bound DNA 4- to 7
      fold or 20- to 30-fold less well, respectively, than the wild-type protein did.
      The most severe point mutants showed residual DNA binding similar to that of a
      truncated protein which lacks the entire 13 carboxy-terminal residues. All of the
      point mutants were able to interact with Vp1, indicating that the two signals
      within this region are mediated by different residues. When the mutations were
      placed into the context of the viral DNA and introduced into cells, all the
      structural proteins were expressed and localized correctly. Not all, however,
      were viable: mutant genomes whose Vp2/3 bound DNA with intermediate affinities
      formed plaques just as well as wild-type SV40 DNA did, but three mutants showing
      greatly reduced DNA binding failed to form plaques at all. These results are
      consistent with the hypothesis that Vp2/3 plays an essential role in SV40 virion
      assembly in the nucleus.

PMID- 7815492
TI  - Structural analyses of the Epstein-Barr virus BamHI A transcripts.
AB  - Epstein-Barr virus (EBV) gene expression in nasopharyngeal carcinoma (NPC)
      includes abundant rightward transcription of the BamHI A fragment, consisting of
      mRNAs ranging in size from approximately 4.0 to 8.0 kb. These transcripts include
      several distinctly spliced forms which are 3'-end coterminal and contain the
      BamHI A rightward frame 0 (BARF0) open reading frame (ORF) in the final exon.
      BamHI A transcription is detected at a lower level of expression in EBV-infected
      lymphoid cells. In this study, cDNA cloning, reverse transcription-based PCR, and
      Northern (RNA) blotting were used to further define the structures of the BamHI A
      transcripts and to characterize their expression in different EBV-infected
      tissues. Three BamHI A cDNAs isolated from a passaged NPC represent previously
      unidentified mRNAs that contain BARF0 and additional ORFs encoded by multiple
      exons, including one which extends the size of the BARF0 ORF from 174 to 279
      codons. The distinct exons were detected in multiple, differently sized mRNAs,
      indicating that these transcripts have complex patterns of alternate splicing. In
      support of this finding, 5'-end analysis confirmed the presence of a previously
      reported start site and also identified a subset of transcripts of 4.8 kb and
      larger that initiate further 5' to this site. In addition, 3'-end analysis
      identified heterogeneous 3'-end processing in all of the BamHI A mRNAs, resulting
      in transcripts that either contain the entire BARF0 ORF or are cleaved and
      polyadenylated 5' of the stop codon. Finally, the expression of multiple,
      distinctly spliced BamHI A transcripts was consistently detected in a wide range
      of EBV-infected samples, including NPC, Burkitt's lymphoma, and parotid carcinoma
      biopsy samples, and in type I and type III Burkitt's lymphoma lines and type III
      lymphoblastoid cell lines. This complex pattern of start site selection,
      alternate splicing, and heterogeneous 3'-end processing is likely to regulate the
      expression in vivo of the ORFs encoded by the EBV BamHI A transcripts.

PMID- 7815493
TI  - Structural interactions between retroviral Gag proteins examined by cysteine
      cross-linking.
AB  - We have examined structural interactions between Gag proteins within Moloney
      murine leukemia virus (M-MuLV) particles by making use of the cysteine-specific
      cross-linking agents iodine and bis-maleimido hexane. Virion-associated wild-type
      M-MuLV Pr65Gag proteins in immature particles were intermolecularly cross-linked
      at cysteines to form Pr65Gag oligomers, from dimers to pentamers or hexamers.
      Following a systematic approach of cysteine-to-serine mutagenesis, we have shown
      that cross-linking of Pr65Gag occurred at cysteines of the nucleocapsid (NC) Cys
      His motif, suggesting that the Cys-His motifs within virus particles are packed
      in close proximity. The M-MuLV Pr65Gag protein did not cross-link to the human
      immunodeficiency virus Pr55Gag protein when the two molecules were coexpressed,
      indicating either that they did not coassemble or that heterologous Gag proteins
      were not in close enough proximity to be cross-linked. Using an assembly
      competent, protease-minus, cysteine-minus Pr65Gag protein as a template, novel
      cysteine residues were generated in the M-MuLV capsid domain major homology
      region (MHR). Cross-linking of proteins containing MHR cysteines showed above
      background levels of Gag-Gag dimers but also identified a novel cellular factor,
      present in virions, that cross-linked to MHR residues. Although the NC cysteine
      mutation was compatible with M-MuLV particle assembly, deletions of the NC domain
      were not tolerated. These results suggest that the Cys-His motif is held in close
      proximity within immature M-MuLV particles by interactions between CA domains
      and/or non-Cys-His motif domains of the NC.

PMID- 7815494
TI  - Modulation of the trans-suppression activity of hepatitis C virus core protein by
      phosphorylation.
AB  - We previously demonstrated that the core protein of hepatitis C virus (HCV) can
      suppress gene expression and replication of hepatitis B virus (HBV) in a human
      hepatoma cell line (HuH-7). In this study, we have characterized the
      phosphorylation property of HCV core protein and examined the effect of
      phosphorylation on its suppressive activity of HBV. Our results indicated that
      both the full-length HCV core protein (22 kDa) and its processed or degraded
      forms (14 to 18 kDa) were phosphorylated in insect cells. As demonstrated by
      using the glutathione S-transferase fusion protein expression system and in vitro
      transcription and translation system, the phosphorylation of HCV core protein was
      carried out by protein kinase A (PKA) and protein kinase C (PKC) in vitro. In
      both kinase reactions, it was determined that the phosphorylated amino acid was a
      serine residue. The potential phosphorylated sites in core protein were
      identified as residues Ser-53 and Ser-116 for PKA and Ser-53 and Ser-99 for PKC.
      Comparison of the phosphorylation intensities of the wild type and Ser mutants
      suggested that Ser-99 and Ser-116 were the major phosphorylation sites for PKC
      and PKA, respectively. The phosphorylation of Ser-99 and Ser-116, but not Ser-53,
      in HCV core protein was essential for the suppressive activity of HCV core
      protein on HBV gene expression and replication in HuH-7 cells. Mutation of the
      former two serine residues to alanine or aspartate residues led to a drastic loss
      of the inhibitory effects of HCV core protein on HBV gene expression (both
      transcription and antigen production) and pregenomic RNA encapsidation, as well
      as the release of HBV virus particles. In contrast, the Ser-53 mutant conferred
      the same level of suppressive activity as the wild type did. This property is in
      accordance with the observation that Ser-99 and Ser-116 are the predominant
      phosphorylation sites in the HCV core construct. All serine mutants (including
      those with mutations in PKA, PKC, and both kinase recognition sites) of HCV core
      protein retained the ability to translocate into the nucleus. Furthermore, wild
      type HCV core protein diminished its suppressive activity when cells were treated
      with PKA or PKC inhibitor. In conclusion, HCV core protein is a phospho-protein
      and in HuH-7 cells, its trans suppression of HBV gene expression and replication
      is positively regulated by PKA and PKC. The role of phosphorylation in the
      control of trans-suppressive activity cannot be reproduced by introducing an
      acidic residue.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7815495
TI  - A minor tyrosine phosphorylation site located within the CAIN domain plays a
      critical role in regulating tissue-specific transformation by erbB kinase.
AB  - Avian c-erbB encodes a protein that is homologous to the human epidermal growth
      factor receptor. Truncation of the amino-terminal, ligand-binding domain of this
      receptor results in an oncogene product which is a potent inducing agent for
      erythroleukemias but not fibrosarcomas in chickens. Here we show that mutation of
      a single tyrosine residue, p5, in the carboxyl terminus of the erbB oncogene
      product allows it to become sarcomagenic in vivo and to transform fibroblasts in
      vitro. Mutations of other autophosphorylation sites do not generate comparable
      effects. The increased transforming activity of the p5 mutant is accompanied by
      an elevated level of mitogen-activated protein kinase phosphorylation. By analogy
      to the human epidermal growth factor receptor, p5 is a minor autophosphorylation
      site and is located in a domain known to be involved in regulating calcium influx
      and receptor internalization (CAIN domain). This area of the erbB product has
      been found to be repeatedly deleted in various sarcomagenic avian
      erythroblastosis virus isolates. We precisely deleted the CAIN domain and also
      made point mutations of the acidic residues within the CAIN domain. In both
      cases, fibroblast-transforming potential is activated. We interpret these data to
      mean that p5 and its surrounding region negatively regulate fibroblast
      transforming and sarcomagenic potential. To our knowledge, this represents the
      first point mutation of an autophosphorylation site that activates erbB
      oncogenicity.

PMID- 7815496
TI  - Phenotypic mixing of rodent but not avian hepadnavirus surface proteins into
      human hepatitis B virus particles.
AB  - The virus family Hepadnaviridae comprises two genera: orthohepadnaviruses
      isolated from humans (hepatitis B virus [HBV]) and rodents (e.g., woodchuck
      hepatitis virus [WHV]) and avihepadnaviruses isolated from birds (e.g., duck
      hepatitis B virus [DHBV]). They carry in their envelopes two (DHBV) or three (HBV
      and WHV) coterminal proteins referred to as small (S), middle (M), or large (L)
      surface protein. These proteins are also secreted from infected cells as subviral
      particles consisting of surface protein and lipid (e.g., 20-nm hepatitis B
      surface antigen for HBV). To investigate the assembly of these proteins, we asked
      whether surface proteins from different hepadnaviruses are able to mix
      phenotypically with each other. By coexpression and coimmunoprecipitation with
      species-specific antibodies, we could show the formation of mixed subviral
      particles and disulfide-linked heterodimers between the WHV S and HBV M proteins
      whereas the DHBV and HBV surface proteins did not coassemble. Complementation of
      HBV genomes defective in expressing the S or L protein and therefore incompetent
      to form virions was possible with the closely related WHV S protein or a WHV pre
      S-HBV S chimera, respectively, but not with the less related DHBV S or L protein
      or with a DHBV L-HBV S chimera. The results suggest that the assembly of HBV
      subviral particles and virion envelopes requires relatively precise molecular
      interactions of their surface proteins, which are not conserved between the two
      hepadnavirus genera. This contrasts with the ability of, e.g., rhabdoviruses or
      retroviruses, to incorporate envelope proteins even from unrelated viruses.

PMID- 7815497
TI  - Determinants of human immunodeficiency virus type 1 envelope glycoprotein
      oligomeric structure.
AB  - Oligomerization of the human immunodeficiency virus type 1 envelope (env)
      glycoproteins is mediated by the ectodomain of the transmembrane glycoprotein
      gp41. We report that deletion of gp41 residues 550 to 561 resulted in gp41
      sedimenting as a monomer in sucrose gradients, while the gp160 precursor
      sedimented as a mixture of monomers and oligomers. Deletion of the nearby
      residues 571 to 582 did not affect the oligomeric structure of gp41 or gp160, but
      deletion of both sequences resulted in monomeric gp41 and predominantly monomeric
      gp160. Deletion of residues 655 to 665, adjacent to the membrane-spanning
      sequence, partially dissociated the gp41 oligomer while not affecting the gp160
      oligomeric structure. In contrast, deletion of residues 510 to 518 from the
      fusogenic hydrophobic N terminus of gp41 did not affect the env glycoprotein
      oligomeric structure. Even though the mutant gp160 and gp120 molecules were
      competent to bind CD4, the mutations impaired fusion function, gp41-gp120
      association, and gp160 processing. Furthermore, deletion of residues 550 to 561
      or 550 to 561 plus 571 to 582 modified the antigenic properties of the proximal
      residues 586 to 588 and the distal residues 634 to 664. Our results indicate that
      residues 550 to 561 are essential for maintaining the gp41 oligomeric structure
      but that this sequence and additional sequences contribute to the maintenance of
      gp160 oligomers. Residues 550 to 561 map to the N terminus of a putative
      amphipathic alpha-helix (residues 550 to 582), whereas residues 571 to 582 map to
      the C terminus of this sequence.

PMID- 7815498
TI  - The initiation of de novo methylation of foreign DNA integrated into a mammalian
      genome is not exclusively targeted by nucleotide sequence.
AB  - The de novo methylation of foreign DNA integrated into the mammalian genome is a
      fundamental process whose mechanism has not yet been elucidated. We have studied
      de novo methylation in adenovirus type 12 (Ad12) genomes inserted into the
      genomes of Ad12-induced hamster tumor cells. De novo methylation of Ad12 DNA,
      which is not methylated in the virion, is initiated in two paracentrally located
      regions and spreads from there across the integrated Ad12 genomes. (i) After
      extensive cultivation of cloned Ad12-induced hamster tumor cell lines, the same
      segments in integrated Ad12 DNA in different cell lines become methylated or
      remain unmethylated, depending on their positions in the viral genome. (ii) When
      Ad12 DNA or Ad12 DNA fragments are transfected into hamster cells and permanent
      cell lines are established by selection for the cotransfected neomycin
      phosphotransferase gene, patterns of de novo methylation in terminally or
      internally located segments of Ad12 DNA are different from those in Ad12-induced
      tumor cell lines. (iii) A detailed study on the topology of the integrated viral
      genomes in the Ad12-transformed hamster cell lines T637 and A2497-3 and in the
      Ad12-induced hamster tumors T191, T1111(1), and T181 has been performed. Some of
      the integrated viral genomes are inserted into the cellular genome in an
      orientation colinear with the virion genome; others have been rearranged. An
      originally internally located Ad12 DNA segment has become transposed to the left
      terminal sequences of the viral genome in several cell lines and tumors. In the
      complete Ad12 genomes, the internally located PstI-D fragment becomes extensively
      methylated at the 5'-CCGG-3' and 5'-GCGC-3' sequences. When this DNA segment has
      been juxtaposed to the left-terminal, hypomethylated fragment of Ad12 DNA in
      rearranged genomes, the PstI-D fragment remains unmethylated. We therefore reason
      that the initiation of de novo methylation in integrated Ad12 DNA cannot be
      directed exclusively by the nucleotide sequence. Other parameters, such as site
      of integration, conformation of integrates, mode of cell selection, or chromatin
      structure related to transcriptional activity, may play decisive roles.

PMID- 7815500
TI  - Protection against homologous but not heterologous challenge induced by
      inactivated feline immunodeficiency virus vaccines.
AB  - Whole inactivated virus vaccines from the FL4 cell line protected against
      challenge with homologous feline immunodeficiency virus (Petaluma strain) but not
      against a heterologous FIV isolate (GL-8) which is distinct from the Petaluma
      strain in virus neutralization. Protection was associated with a type-specific
      neutralizing antibody response and was retained when the challenge virus was
      propagated in an unrelated cell line.

PMID- 7815499
TI  - Extracellular Vpr protein increases cellular permissiveness to human
      immunodeficiency virus replication and reactivates virus from latency.
AB  - The vpr gene product of human immunodeficiency virus (HIV) and simian
      immunodeficiency virus is a virion-associated regulatory protein that has been
      shown using vpr mutant viruses to increase virus replication, particularly in
      monocytes/macrophages. We have previously shown that vpr can directly inhibit
      cell proliferation and induce cell differentiation, events linked to the control
      of HIV replication, and also that the replication of a vpr mutant but not that of
      wild-type HIV type 1 (HIV-1) was compatible with cellular proliferation (D. N.
      Levy, L. S. Fernandes, W. V. Williams, and D. B. Weiner, Cell 72:541-550, 1993).
      Here we show that purified recombinant Vpr protein, in concentrations of < 100
      pg/ml to 100 ng/ml, increases wild-type HIV-1 replication in newly infected
      transformed cell lines via a long-lasting increase in cellular permissiveness to
      HIV replication. The activity of extracellular Vpr protein could be completely
      inhibited by anti-Vpr antibodies. Extracellular Vpr also induced efficient HIV-1
      replication in newly infected resting peripheral blood mononuclear cells.
      Extracellular Vpr transcomplemented a vpr mutant virus which was deficient in
      replication in promonocytic cells, restoring full replication competence. In
      addition, extracellular Vpr reactivated HIV-1 expression in five latently
      infected cell lines of T-cell, B-cell, and promonocytic origin which normally
      express very low levels of HIV RNA and protein, indicating an activation of
      translational or pretranslational events in the virus life cycle. Together, these
      results describe a novel pathway governing HIV replication and a potential target
      for the development of anti-HIV therapeutics.

PMID- 7815501
TI  - Regions required for CD4 binding in the external glycoprotein gp120 of simian
      immunodeficiency virus.
AB  - The external domain of the envelope glycoprotein, gp120, of simian
      immunodeficiency virus (SIV) has been expressed as a mature secreted product
      using recombinant baculoviruses and the expressed protein, which has an observed
      molecular mass of 110 kDa, was purified by monoclonal antibody (MAb) affinity
      chromatography. N-terminal sequence analysis showed a signal sequence cleavage
      identity similar to that of the gp120s of both human immunodeficiency virus type
      1 (HIV-1) and HIV type 2. The expressed molecule bound to soluble CD4 with an
      affinity that was approximately 10-fold lower than that of gp120 from HIV-1. A
      screening of the ability of SIV envelope MAbs to inhibit CD4 binding revealed two
      groups of inhibitory MAbs. One group is dependent on conformation, while the
      second group maps to a discrete epitope near the amino terminus. The particular
      role of the V3 loop region of the molecule in CD4 binding was investigated by the
      construction of an SIV-HIV hybrid in which the V3 loop of SIV was precisely
      replaced with the equivalent domain from HIV-1 MN. The hybrid glycoprotein bound
      HIV-1 V3 loop MAbs and not SIV V3 MAbs but continued to bind conformational SIV
      MAbs and soluble CD4 as well as the parent molecule.

PMID- 7815502
TI  - Cytotoxic T cells specific for a single peptide on the M2 protein of respiratory
      syncytial virus are the sole mediators of resistance induced by immunization with
      M2 encoded by a recombinant vaccinia virus.
AB  - We have studied the immunobiology of respiratory syncytial virus (RSV), a major
      cause of respiratory tract morbidity in children. As part of these studies, it
      was previously found that immunization of BALB/c (H-2d) mice with a recombinant
      vaccinia virus (rVV) which encoded the M2 protein of RSV provided complete
      protection against infection with RSV. This protection was transient and
      associated with M2-specific CD8+ T-cell (TCD8+) responses. In this study, we used
      two approaches to demonstrate that expression of an H-2Kd-restricted nonameric
      peptide (Ser Tyr Ile Gly Ser Ile Asn Asn Ile) corresponding to M2 residues 82 to
      90 is necessary and sufficient to induce protective TCD8+ responses. First,
      infection of mice with an rVV which encoded the peptide M2Met82-90 induced levels
      of primary pulmonary TCD8+ and resistance to RSV challenge equivalent to that
      induced by infection with an rVV which expressed the complete M2 protein. Second,
      elimination of peptide binding to Kd by the replacement of Tyr with Arg at amino
      acid position 83 of the full-length protein completely abrogated the ability of
      an rVV-expressing full-length M2 to induce either M2-specific TCD8+ responses or
      resistance to RSV infection. These findings demonstrate that the M2(82-90)
      peptide is the sole determinant of immunity induced in BALB/c mice by the M2
      protein and that a remarkably high level of transient resistance to infection
      with pulmonary virus is associated with TCD8+ responses to a single determinant.

PMID- 7815503
TI  - Characterization of the Epstein-Barr virus proteinase and comparison with the
      human cytomegalovirus proteinase.
AB  - The BVRF2 gene of Epstein-Barr virus (EBV) shows homology to the UL26 and UL80
      genes of herpes simplex virus type 1 (HSV-1) and cytomegalovirus (CMV),
      respectively. These genes are believed to provide a scaffold protein for the
      assembly of capsids leading to the formation of infectious viral particles. We
      have cloned the BVRF2 gene from the B95.8 strain of EBV and shown that the BVRF2
      gene product is a polyprotein capable of autoproteolytic cleavage. Two Ala-Ser
      containing recognition sequences were identified in the BVRF2 polyprotein at
      amino acid positions 568/569 and 570/571 where this cleavage was expected to
      occur. Here, we show that EBV proteinase is capable of cleaving at the first Ala
      Ser bond but not the second. Comparison of the processing of the EBV and human
      CMV assembly domains in vitro by either EBV or human CMV proteinase revealed
      that, while both proteinases could cleave their native assembly domain, only EBV
      proteinase was able to cleave the assembly domain of the other virus.

PMID- 7815504
TI  - Neutralization of respiratory syncytial virus after cell attachment.
AB  - Little is known about the mechanisms of antibody-mediated neutralization of
      respiratory syncytial virus (RSV) which causes recurrent infections in human
      despite the virtually universal presence of neutralizing serum antibodies. Human
      serum neutralization titers showed strong correlation with post-cell-attachment
      neutralizing titers for both RSV-convalescent sera and control sera but showed
      less strong correlation with cell-attachment blocking titers. Neutralization was
      effective for the first 60 min of infection, indicating that immune serum
      mediated neutralization of RSV infection largely involves inhibition of early
      events following cell attachment.

PMID- 7815505
TI  - Influenza B viruses with site-specific mutations introduced into the HA gene.
AB  - We have succeeded in engineering changes into the genome of influenza B virus.
      First, model RNAs containing the chloramphenicol acetyltransferase gene flanked
      by the noncoding sequences of the HA or NS genes of influenza B virus were
      transfected into cells which were previously infected with an influenza B helper
      virus. Like those of the influenza A viruses, the termini of influenza B virus
      genes contain cis-acting signals which are sufficient to direct replication,
      expression, and packaging of the RNA. Next, a full-length copy of the HA gene
      from influenza B/Maryland/59 virus was cloned. Following transfection of this
      RNA, we rescued transfectant influenza B viruses which contain a point mutation
      introduced into the original cDNA. A series of mutants which bear deletions or
      changes in the 5' noncoding region of the influenza B/Maryland/59 virus HA gene
      were constructed. We were able to rescue viruses which contained deletions of 10
      or 33 nucleotides at the 5' noncoding region of the HA gene. The viability of
      these viruses implies that this region of the genome is flexible in sequence and
      length.

PMID- 7815506
TI  - Plasmid maintenance of derivatives of oriP of Epstein-Barr virus.
AB  - oriP is the origin of plasmid replication of Epstein-Barr virus. Replication from
      oriP requires both the cis-acting elements (the family of repeats and the dyad
      symmetry element) and the viral origin-binding protein, EBNA-1. The ability of
      plasmids containing oriP to be maintained stably in EBNA-1-positive cells
      reflects the efficiency both of their replication and of their segregation each
      cell cycle. The efficiency of plasmid maintenance was determined for plasmids
      containing derivatives of oriP with one copy of the dyad symmetry element and two
      copies of the family of repeats by measuring the rate at which they were lost
      from cells in the absence of selection. These measurements demonstrated that
      plasmids with derivatives of oriP with two copies of the family of repeats in one
      orientation are maintained only slightly less efficiently than is wild-type oriP.
      To determine whether plasmid maintenance could be affected by reinitiation at the
      dyad symmetry element (T. A. Gahn and C. L. Schildkraut, Cell 58:527-535, 1989),
      plasmids containing derivatives of oriP with two copies of the dyad symmetry
      element and one copy of the family of repeats were compared with plasmids
      containing wild-type oriP in EBNA-1-positive cells. These measurements showed
      that plasmids containing a derivative of oriP with two copies of the dyad
      symmetry element are maintained as efficiently as is wild-type oriP and are not
      amplified relative to wild-type oriP. These observations indicate that the trans
      acting factors that regulate DNA to replicate once per S phase are insensitive to
      multiple cis-acting regulatory sites within a replicon.

PMID- 7815507
TI  - Induction of interleukin-10 by human immunodeficiency virus type 1 and its gp120
      protein in human monocytes/macrophages.
AB  - In this study, we evaluated the effects of human immunodeficiency virus type 1
      (HIV-1) and its gp120 protein on interleukin-10 (IL-10) expression in cultured
      human monocytes/macrophages. Infection of either 1-day monocytes or 7-day
      monocyte-derived macrophages with HIV-1 strain Ba-L resulted in clear-cut
      accumulation of IL-10 mRNA at 4 and 24 h. Likewise, treatment of these cells with
      recombinant gp120 induced IL-10 mRNA expression and caused a marked increase in
      IL-10 secretion. Monoclonal antibodies to gp120 strongly inhibited recombinant
      gp120-induced IL-10 secretion by monocytes/macrophages. Moreover, the addition of
      IL-10 to monocytes/macrophages resulted in a significant inhibition of HIV-1
      replication 7 and 14 days after infection. On the whole, these results indicate
      that HIV-1 (possibly through its gp120 protein) up-regulates IL-10 expression in
      monocytes/macrophages. We suggest that in vivo production of IL-10 by HIV-primed
      monocytes/macrophages can play an important role in the early response to HIV-1
      infection.

PMID- 7815508
TI  - Induction of cytokines in mice with parainfluenza pneumonia.
AB  - The possible involvement of cytokines in the acute viral pneumonia induced by the
      murine parainfluenza type 1 virus, Sendai virus, was studied. Cytokine profiles
      for both the respiratory tract and the draining mediastinal lymph node (MLN) of
      virus-infected C57BL/6J mice were quantified by using the single-cell cytokine
      (ELISPOT) assay with freshly isolated cell populations and enzyme-linked
      immunosorbent assay for lung lavage fluids and culture supernatants. Maximal
      levels of interleukin 2 (IL-2), gamma interferon (IFN-gamma), tumor necrosis
      factor, IL-6, and IL-10 were detected at the inflammatory site 7 to 10 days after
      infection, about the time that virus is cleared from the lung. The frequencies of
      cells producing IL-2, IL-4, IL-6, IL-10, IFN-gamma, and tumor necrosis factor
      were much higher for the bronchoalveolar lavage (BAL) cell population than for
      the MLN cell population. Cytokine production after in vitro restimulation of MLN
      cells was dominated by IL-2 and IFN-gamma, with low levels of IL-10 and IL-6 also
      being present. Most of the cytokine was produced by the CD4+ cells, although the
      CD8+ subset was also involved. No IL-4 was found in the BAL fluid or in culture
      supernatants from restimulated BAL or MLN cells, although a high frequency of IL
      4-producing cells was demonstrated in the BAL population by ELISPOT analysis.

PMID- 7815509
TI  - Effects of the simian virus 40 origin of replication on transcription from the
      human immunodeficiency virus type 1 promoter.
AB  - Positive and negative effects of DNA replication on gene transcription have been
      documented in a variety of systems. We examined the effects of the simian virus
      40 (SV40) origin of replication on transcription from the human immunodeficiency
      virus type 1 (HIV-1) promoter, using a transient expression assay in COS-1 cells.
      The basal activity and Tat transactivation of the HIV promoter were greatly
      stimulated by the SV40 origin of replication independent of its position relative
      to the long terminal repeat. These effects were abolished by mutational
      inactivation of the SV40 origin and were reduced by a DNA replication inhibitor.
      The magnitude of promoter activation exceeded the increment expected from the
      increase in template number resulting from DNA replication. The SV40 T-antigen
      induced DNA replication augmented the generation of both processive and
      nonprocessive HIV long terminal repeat-directed transcripts, and Tat primarily
      enhanced the initiation of those transcripts that were destined to be efficiently
      elongated. Our data suggest that the HIV promoter displays greater
      transcriptional activity on replicative DNA templates. This property may
      influence the activity of integrated HIV provirus and its transition from latency
      to productive infection.

PMID- 7815510
TI  - Intrauterine transmission of human T-cell leukemia virus type I in rats.
AB  - To analyze intrauterine transmission, MT-2 cells, a human T-cell line producing
      human T-cell leukemia virus type I (HTLV-I), were injected into eight pregnant
      F344 rats, and cesarean section was performed at day 23 of pregnancy. HTLV-I
      provirus was detected by PCR in the liver and spleen taken from one of the eight
      fetuses. Moreover, 71 offspring were delivered by cesarean section from the
      remaining seven dams and fostered by seven normal rats. HTLV-I provirus was
      detected in peripheral blood mononuclear cells in 2 of the 71 offspring 4 weeks
      after cesarean section. These results indicate for the first time the
      intrauterine transmission of HTLV-I. To confirm the postnatal transmission, MT-2
      cells were injected into a dam within 24 h after delivery, and six offspring were
      fostered by this dam. HTLV-I provirus was detected in peripheral blood
      mononuclear cells of all six offspring. This animal model may be useful for
      analysis and prevention of mother-to-child transmission of HTLV-I.

PMID- 7815511
TI  - Induction of protective cytotoxic T cells to murine cytomegalovirus by using a
      nonapeptide and a human-compatible adjuvant (Montanide ISA 720).
AB  - The use of synthetic peptides representing cytotoxic T-cell (CTL) epitopes for
      human vaccination requires the identification of a suitable adjuvant formulation.
      A single immunization with Montanide ISA720/tetanus toxoid/YPHFMPTNL protected
      mice against murine cytomegalovirus and induced epitope-specific CTL. Such
      formulations will find application in peptide-based CTL anti-viral vaccines.

PMID- 7815512
TI  - The transcripts from the sequences flanking the short component of Marek's
      disease virus during latent infection form a unique family of 3'-coterminal RNAs.
AB  - We have constructed a cDNA library using poly(A)+ RNA from the stably transformed
      Marek's disease virus cell line MKT-1 and isolated cDNAs specific to the short
      internal repeat region of the BamHI-A fragment of the viral genome. Four distinct
      classes of cDNA were identified through sequence analysis of the 5' and 3'
      termini of each clone isolated, and a representative of each class was chosen for
      complete sequencing. These cDNAs were mapped on the basis of the genomic
      nucleotide sequence of this region, and a family of 3'-coterminal overlapping
      transcripts consisting of several highly spliced species, was identified. PCR was
      used to amplify specific regions of each cDNA, which were subcloned and used to
      generate riboprobes. These riboprobes hybridized to a variety of transcripts in
      poly(A)+ RNA fractions isolated from cells either lytically or latently infected
      with Marek's disease virus.

PMID- 7815513
TI  - Effect of protein kinase C inhibitors on the antiviral activity of human alpha
      interferon in herpes simplex virus-infected human neuroblastoma cells.
AB  - Pretreatment of human neuroblastoma cells with an inhibitor of protein kinase C
      (PKC), staurosporine or H-7, prior to the addition of human alpha interferon
      (HuIFN-alpha), recombinant HuIFN-alpha, or recombinant HuIFN-beta blocked the
      inhibitory effect of these IFNs on the release of infectious herpes simplex virus
      type 1 from treated cells. In addition, staurosporine blocked the inhibitory
      effect of HuIFNs on the expressions of herpes simplex type 1 glycoproteins B, C,
      and D in treated neuroblastoma cells. Furthermore, addition of HuIFNs resulted in
      an increased expression of PKC in treated neuroblastoma cells. These results
      suggest that inhibitors of PKC block the expression of HuIFN-induced genes in
      treated human neuroblastoma cells. Thus, the activation of PKC is an important
      step in the HuIFN-treated cells of neuronal origin.

PMID- 7815514
TI  - Two E2 binding sites alone are sufficient to function as the minimal origin of
      replication of human papillomavirus type 18 DNA.
AB  - Replication of papillomaviruses requires an origin of replication and two virus
      encoded proteins, E1 and E2. Using a transient replication assay for human
      papillomavirus type 18 (HPV-18) DNA, we have found that two adjacent sequences
      present within the origin of replication can independently support replication.
      The first, a 77-bp region, contains one E2 binding site (E2BS) and a 16-bp
      inverted repeat element that probably corresponds to the E1 binding site (E1BS).
      The other, an 81-bp region, includes two E2BS but lacks the putative E1BS. A
      synthetic 33-bp oligonucleotide containing two high-affinity E2BS was also found
      to function as an origin of replication. Replication of all these plasmids was
      absolutely dependent on the presence of the HPV-18 E1 and E2 proteins. The HPV-1a
      E1 and E2 proteins were also found to support replication of a plasmid containing
      the complete HPV-18 origin but failed to replicate a plasmid containing two E2BS
      alone. Our results suggest that the E2 protein can target E1 to the origin
      through the formation of an E1-E2 complex which is likely to be involved the
      initiation of replication.

PMID- 7815515
TI  - Evidence for coinfection by multiple strains of human immunodeficiency virus type
      1 subtype B in an acute seroconvertor.
AB  - Sequences encoding the envelope glycoprotein of human immunodeficiency virus type
      1 (HIV-1) were amplified by PCR from plasma and peripheral blood mononuclear
      cells obtained at four time points from an acute seroconvertor. Genetic analyses,
      including nucleotide sequencing and heteroduplex mobility studies, showed that
      the patient harbored three distinct populations of HIV-1 clade B envelope
      sequences, with nucleotide distances ranging from 9.2 to 17.2%. One population of
      sequences was clearly distinguishable from the others on the basis of
      phylogenetic analysis. In addition, sequences suggesting recombination between
      two of the three distinct viral populations were also found. This case of acute
      seroconversion provides clear and conclusive evidence that coinfection by
      multiple HIV-1 strains can indeed occur in vivo.

PMID- 7815517
TI  - A deletion at the UL/IR junction reduces pseudorabies virus neurovirulence.
AB  - A recombinant pseudorabies virus (PRV), designated LLT beta delta 2, which
      contains a 3-kbp deletion spanning the junction of the unique long and internal
      repeat sequences was constructed. Compared with the parental strain and a virus
      rescued for the deleted sequences, LLT beta delta 2 exhibited similar replication
      characteristics in tissue culture. When inoculated intranasally in swine, LLT
      beta delta 2 was significantly reduced in virulence and did not produce
      neurological signs characteristic of PRV infection. LLT beta delta 2 replicated
      efficiently at the site of inoculation and in peripheral nervous tissues, but
      replication was restricted in the central nervous system. These results indicate
      the presence of a PRV neurovirulence determinant in the vicinity of the junction.

PMID- 7815516
TI  - Potential role of natural killer cells in controlling tumorigenesis by human T
      cell leukemia viruses.
AB  - Human T-cell leukemia virus (HTLV) is the etiologic agent of adult T-cell
      leukemia (ATL), a malignancy of T lymphocytes that is characterized by a long
      latency period after virus exposure. Intraperitoneal inoculation of severe
      combined immunodeficient (SCID) mice with HTLV-transformed cell lines and ATL
      tumor cells was employed to investigate the tumorigenic potential of HTLV type I
      (HTLV-I)-infected cells. In contrast to inoculation of ATL (RV-ATL) cells into
      SCID mice, which resulted in the formation of lymphomas, inoculation of HTLV-I-
      and HTLV-II-transformed cell lines (SLB-I and JLB-II cells, respectively) did not
      result in tumor formation. Immunosuppression of SCID mice, either by whole-body
      irradiation or by treatment with an antiserum, anti-asialo GM1 (alpha-AGM1),
      which transiently abrogates natural killer cell activity in vivo, was necessary
      to establish the growth of tumors derived from HTLV-transformed cell lines. PCR
      and flow cytometric studies reveal that HTLV-I-transformed cells are eliminated
      from the peritoneal cavities of inoculated mice by 3 days postinoculation; in
      contrast, RV-ATL cells persist and are detected until the mice succumb to
      lymphoma development. The differing behaviors of HTLV-infected cell lines and ATL
      tumor cells in SCID mice suggest that ATL cells have a higher tumorigenic
      potential in vivo than do HTLV-infected cell lines because of their ability to
      evade natural killer cell-mediated cytolysis.

PMID- 7815518
TI  - Intracellular neutralization of influenza virus by immunoglobulin A anti
      hemagglutinin monoclonal antibodies.
AB  - Traditionally, immunoglobulin A (IgA) was thought to neutralize virus by forming
      complexes with viral attachment proteins, blocking attachment of virions to host
      epithelial cells. Recently we have proposed an intracellular action for dimeric
      IgA, which is actively transported through epithelial cells by the polymeric
      immunoglobulin receptor (pIgR), in that it may be able to bind to newly
      synthesized viral proteins within the cell, preventing viral assembly. To this
      effect, we have previously demonstrated that IgA monoclonal antibodies against
      Sendai virus, a parainfluenza virus, colocalize with the viral hemagglutinin
      neuraminidase protein within infected epithelial cells and reduce intracellular
      viral titers. Here we determine whether IgA can interact with influenza virus
      hemagglutinin (HA) protein within epithelial cells. Polarized monolayers of Madin
      Darby canine kidney epithelial cells expressing the pIgR were infected on their
      apical surfaces with influenza virus A/Puerto Rico/8-Mount Sinai. Polymeric IgA
      anti-HA, but not IgG anti-HA, delivered to the basolateral surface colocalized
      with HA protein within the cell by immunofluorescence. Compared with those of
      controls, viral titers were reduced in the supernatants and cell lysates from
      monolayers treated with anti-HA IgA but not with anti-HA IgG. Furthermore, the
      addition of anti-IgA antibodies to supernatants did not interfere with the
      neutralizing activity of IgA placed in the basal chamber, indicating that IgA was
      acting within the cell and not in the extracellular medium to interrupt viral
      replication. Thus, these studies provide additional support for the concept that
      IgA can inhibit replication of microbial pathogens intracellularly.

PMID- 7815519
TI  - Effects of second-site mutations on dominant interference by a human
      immunodeficiency virus type 1 envelope glycoprotein mutant.
AB  - We have demonstrated previously that a human immunodeficiency virus type 1 (HIV
      1) envelope glycoprotein containing a Val-to-Glu substitution at the second amino
      acid of the transmembrane glycoprotein gp41 (termed the 41.2 mutant) dominantly
      interferes with wild-type envelope-mediated syncytium formation and virus
      infectivity. To understand the mechanism by which the 41.2 mutant exerts the
      dominant interfering phenotype and thereby determine further how the mutant might
      be used as an inhibitor of viral spread, additional mutations were made in the
      envelope gene, and the effects of these mutations on interference were
      determined. It was found that processing of the 41.2 mutant glycoprotein in gp120
      and gp41 subunits and a functional CD4-binding domain are necessary for the
      interfering phenotype to be exhibited fully. However, neither a wild-type V3 loop
      nor the gp41 cytoplasmic tail is necessary for efficient interference. In
      addition, it was determined that the dominant interfering phenotype is not
      conferred exclusively by the glutamate substitution at amino acid 2 of gp41,
      since a substitution with a basic residue at this position also results in a
      dominant interfering envelope glycoprotein.

PMID- 7815520
TI  - cDNA sequence analysis confirms that the etiologic agent of callitrichid
      hepatitis is lymphocytic choriomeningitis virus.
AB  - Callitrichid hepatitis is an infection of New World primates caused by an
      arenavirus, currently referred to as callitrichid hepatitis virus, that is
      closely related to lymphocytic choriomeningitis virus (LCMV). We have cloned and
      sequenced the GP-C gene of callitrichid hepatitis virus and found that the cDNA
      sequence is 84 to 86% identical to those of the GP-C genes of LCMV strains
      Armstrong and WE, while the deduced amino acid sequence is 95 to 96% identical to
      those of the GP-C gene products of the same strains. This high degree of
      similarity indicates that the etiologic agent of callitrichid hepatitis is in
      fact LCMV. The wide geographic distribution of callitrichid hepatitis outbreaks
      in the United States serves as a reminder that LCMV is also a human pathogen
      whose public health implications are not well understood.

PMID- 7815521
TI  - Identification of a new viral protein containing CAp30 and NCp10 sequences in
      murine and feline leukemia retroviruses.
AB  - Because Pr65gag is in part located in the nucleus and contains a putative
      bipartite nuclear targeting signal, we investigated the cellular location and
      structure of P55gag, a gag-encoded polyprotein known to lack the nucleocapsid
      (NC) protein NCp10. P55gag was found to be restricted to the cytoplasm of Moloney
      murine leukemia virus-infected cells. Of interest, P55gag was produced in cells
      infected by a viral protease deletion mutant and by a recombinant murine sarcoma
      virus known to lack the protease gene. Surprisingly, our structural and
      immunological studies indicated that P55gag also lacks carboxy-terminal residues
      of CAp30. During the course of studying P55gag, we detected a new viral protein
      within purified virus particles that contained NCp10 tryptic peptide sequences
      and a CAp30 tryptic peptide lacking in P55gag. This viral protein, which we have
      named nucleocapsid-related protein (NCRP), also contained antigenic epitopes
      present in CAp30 and NCp10. P55gag- and NCRP-like proteins were also observed in
      AKV murine leukemia virus and feline leukemia virus systems. The precise site of
      cleavage within Pr65gag that produces P55gag and NCRP is unknown but lies
      upstream of the CAp30-NCp10 junction within the carboxy-terminal domain of CAp30.
      The existence of a form of NCp10 containing carboxy-terminal CAp30 sequences
      raises interesting possibilities about its functional role in genomic RNA
      packaging and/or viral RNA dimerization.

PMID- 7815522
TI  - Encapsidation and serial passage of a poliovirus replicon which expresses an
      inactive 2A proteinase.
AB  - The multiple roles of the viral proteinase 2A in poliovirus replication have been
      difficult to assess because, to date, it has not been possible to isolate and
      characterize a viral genome with an inactive 2Apro. We have previously reported
      that a poliovirus replicon containing an inactive 2Apro by virtue of a change at
      amino acid 109 from a cysteine to a serine (C109S) was replication competent when
      transfected into cells previously infected with vaccinia virus (R. Pal-Ghosh and
      C. D. Morrow, J. Virol. 67:4621-4629, 1993). To further develop this system, we
      have used a poliovirus replicon which contains the human immunodeficiency virus
      type 1 (HIV-1) gag gene positioned between nucleotides 1174 and 2470 of the
      poliovirus genome and have engineered a second mutation within this replicon to
      change the codon for amino acid 109 of the 2Apro from cysteine to serine
      (2AC109S). Transfection of this replicon into cells previously infected with
      vaccinia virus results in the replication and expression of a protein with a
      molecular mass consistent with that of a P1-HIV-1 Gag-2A fusion protein. Using a
      recently described complementation system which relies on the capacity of a
      recombinant vaccinia virus (VV-P1) to provide the capsid precursor (P1) in trans
      (D. C. Ansardi, D. C. Porter, and C. D. Morrow, J. Virol. 67:3684-3690, 1993; and
      D. C. Porter, D. C. Ansardi, W. S. Choi, and C. D. Morrow, J. Virol. 67:3712
      3719, 1993), we have encapsidated this replicon containing the 2AC109S mutation.
      By using reverse transcription PCR, we demonstrated that after 15 serial passages
      the encapsidated replicon still contained the 2AC109S mutation. Infection of
      cells with a stock of encapsidated replicon, either in the presence or in the
      absence of vaccinia virus, resulted in the expression of the P1-HIV-1 Gag-2A
      fusion protein. Expression of the P1-HIV-1 Gag fusion protein in cells infected
      with the encapsidated replicon containing the 2AC109S mutation was reduced
      compared with the expression of P1-HIV-1 Gag in those cells infected with a
      replicon containing a wild type 2A gene. The protein expression and replication
      of the replicon RNA in cells containing the 2AC109S mutation was maintained for a
      longer period of time than for the replicons containing the wild-type 2A gene,
      possibly because of a reduced cytopathic effect.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7815523
TI  - Simian immunodeficiency virus SIVmac chimeric virus whose env gene was derived
      from SIV-encephalitic brain is macrophage-tropic but not neurovirulent.
AB  - We inoculated four rhesus macaques with molecularly cloned simian
      immunodeficiency virus SIVmac239/17E env, a chimeric virus whose env gene was
      derived from the brain of an SIV-encephalitic macaque. Blood and lymphoid tissues
      had high frequencies of infected cells. The virus was neuroinvasive, but
      productive virus replication did not occur in the brain, and animals did not
      develop encephalitis.

PMID- 7815524
TI  - Sequence analysis of the downstream 5' nontranslated region of seven echoviruses
      with different neurovirulence phenotypes.
AB  - The downstream 5' nontranslated regions of seven echoviruses with different
      neurovirulent phenotypes were amplified and sequenced. Neurovirulent echovirus
      serotypes 4, 6, 9, 11, and 30 were identical to the putative poliovirus in 18S
      rRNA binding sequence and the flanking conserved sequences. Less neurovirulent
      echoviruses, serotypes 2 and 12, exhibited variations within these regions.

PMID- 7815525
TI  - Phylogenetic relationship and geographic distribution of multiple human T-cell
      lymphotropic virus type II subtypes.
AB  - The current env-based subtyping of human T-cell lymphotropic virus type II (HTLV
      II) identifies only two heterogenetic groups, HTLV-IIa and HTLV-IIb. To better
      understand the genetic diversity and phylogeny of HTLV-II, we examined the most
      divergent genomic region of HTLV-II, the long terminal repeat, by using
      restriction fragment length polymorphism (RFLP) and sequence analysis. Long
      terminal repeat sequences were amplified from peripheral blood mononuclear cells
      by PCR and digested with seven restriction endonucleases that differentiated HTLV
      II into five HTLV-IIa (IIa0 to IIa4) and six HTLV-IIb (IIb0 to IIb5) restriction
      types, with HTLV-IIa0 and HTLV-IIb0 being prototypes for the MoT and NRA
      isolates, respectively. We examined 169 HTLV-II-infected samples, including 123
      from blood donors and intravenous drug users (IDU) from the Americas, 16 from IDU
      from Europe, and 30 from Amerindians. Of the 169 samples, 109 (64.5%) were
      categorized as HTLV-IIa and 60 (35.5%) were categorized as HTLV-IIb. The
      predominant restriction types seen among the U.S. blood donors and U.S. IDU were
      IIa0 (68.7%) and IIb4 (10.4%). Four Spanish and seven Italian samples were IIb4,
      while five Norwegian samples were IIa2. Twelve Guaymi and all ten Seminole
      samples were single restriction types (IIb1 and IIb5, respectively), whereas the
      two Navajo and six Pueblo samples had a mixture of restriction types IIa0, IIa4,
      and IIb5. Of the HTLV-IIb restriction types observed in the U.S. non-Indians,
      42.8% appear to have originated from the North Amerindian (IIb5), while 57.2%
      were similar to the European IIb4 restriction type. Sequences of 15 selected HTLV
      II samples were determined and phylogenetically compared with 7 previously
      published HTLV-II LTR sequences. The derived topologies revealed three HTLV-IIa
      phylogroups (A-I to A-III) and four HTLV-IIb phylogroups (B-I to B-IV).
      Furthermore, the HTLV-IIa phylogroups appear to have evolved from the HTLV-IIb
      phylogroups. In the HTLV-IIa cluster, a Navajo (A-I) and a Brazilian (A-II)
      sequence formed separate phylogroups, while the remaining IIa sequences formed a
      single phylogroup (A-III). The four HTLV-IIb phylogroups were represented
      predominantly by a New York IDU (B-I), European IDU (B-II), North Amerindian and
      NRA (B-III), and Central Guaymi Indian (B-IV) sequence(s). Comparison of the
      phylogenetic data with the RFLP results revealed that results of the two methods
      correlated completely, demonstrating the ability of the RFLP method to predict
      the phylogroup of HTLV-II-infected samples accurately and quickly. GENBANK/U10258

PMID- 7815526
TI  - Spread of a neurotropic coronavirus to spinal cord white matter via neurons and
      astrocytes.
AB  - Mouse hepatitis virus strain JHM (MHV-JHM) causes a chronic encephalomyelitis in
      susceptible mice, with histological evidence of demyelination in the spinal cord.
      After intranasal inoculation, virus spreads retrogradely to several brain
      structures along neuroanatomic projections to the main olfactory bulb. In the
      absence of experimental intervention, mice become moribund before the spinal cord
      is infected. In this study, infusions of anti-MHV neutralizing monoclonal
      antibodies were administered to protect mice from the MHV-JHM-induced acute
      encephalitis and to allow survival until virus spread to the spinal cord. Under
      these conditions, virus was observed to enter specific layers (primarily laminae
      V to VII) in the gray matter of the upper spinal cord, consistent with
      transneuronal spread. While the brain structures which are the sources for virus
      spread to the spinal cord cannot be determined with certainty, the ventral
      reticular nucleus is likely to be important since it is consistently and
      extensively labeled in all mice and receives projections from subsequently
      infected areas of the spinal cord. After initial entry into the gray matter,
      virus rapidly spread to the white matter of the spinal cord. During the early
      stages of this process, extensive infection of astrocytes was noted, suggesting
      that cell-to-cell spread via these glial cells is an important part of this
      process. Reports from other laboratories using cultured cells strongly suggested
      that astrocytes serve as important regulators of oligodendrocyte function and, by
      extrapolation, have a major role in vivo in the processes of both demyelination
      and remyelination. Thus, our results not only outline the probable pathway used
      by MHV-JHM to infect the white matter of the spinal cord but also, with the
      assumption that infection of astrocytes leads to subsequent dysfunction, raise
      the possibility that infection of these cells contributes to the demyelinating
      process.

PMID- 7815527
TI  - Linker insertion mutations in the human immunodeficiency virus type 1 gag gene:
      effects on virion particle assembly, release, and infectivity.
AB  - The phenotypes of a series of mutant human immunodeficiency virus type 1
      proviruses with linker insertion and deletion mutations within the gag coding
      region were characterized. These mutants were tested for their ability to make
      and release viral particles in COS7 cells and for their viability in vivo. Of the
      12 mutant proviruses, 4 did not make extracellular virion particles when
      transfected into COS7 cells. All four of these mutants had mutations in the C
      terminal domain of CA. These mutants appeared to have defects both in the ability
      to accumulate high-molecular-weight intracellular structures containing Gag and
      Pol products and in the ability to release virion particles. Seven of the mutant
      proviruses retained the ability to make, release, and process virion particles
      from COS7 cells. These particles contained the Env glycoprotein, viral genomic
      RNA, and the mature products of the Gag and Gag-Pol polyproteins, yet they were
      noninfectious or poorly infectious. The defect in these mutants appears to be in
      one of the early steps of the viral life cycle. Thus, multiple regions throughout
      Gag appear to be important in mediating the early steps of the viral life cycle.

PMID- 7815529
TI  - Delay of vaccinia virus-induced apoptosis in nonpermissive Chinese hamster ovary
      cells by the cowpox virus CHOhr and adenovirus E1B 19K genes.
AB  - The infection of vaccinia virus in Chinese hamster ovary (CHO) cells produces a
      rapid shutdown in protein synthesis, and the infection is abortive (R.R.
      Drillien, D. Spehner, and A. Kirn, Virology 111:488-499, 1978; D.E. Hruby, D.L.
      Lynn, R. Condit, and J.R. Kates, J. Gen. Virol. 47:485-488, 1980). Cowpox virus,
      which can productively infect CHO cells, had previously been shown to contain a
      host range gene, CHOhr, which confers on vaccinia virus the ability to replicate
      in CHO cells (D. Spehner, S. Gillard, R. Drillien, and A. Kirn, J. Virol. 62:1297
      1304, 1988). We found that CHO cells underwent apoptosis when infected with
      vaccinia virus. The expression of the CHOhr gene in vaccinia virus allowed for
      the expression of late virus genes. CHOhr also delayed or prevented vaccinia
      virus-induced apoptosis in CHO cells such that there was sufficient time for
      replication of the virus before the cell died. The E1B 19K gene from adenovirus
      also delayed vaccinia virus-induced apoptosis; however, there was no detectable
      expression of late virus genes. Furthermore, E1B 19K also delayed cell death in
      CHO cells which had been productively infected with vaccinia virus. This study
      identifies a new antiapoptotic gene from cowpox virus, CHOhr, for which the
      protein contains an ankyrin-like repeat and shows no significant homology to
      other proteins. This work also indicates that an antiapoptotic gene from one
      virus family can delay cell death in an infection of a virus from a different
      family.

PMID- 7815528
TI  - cis-Acting components of human papillomavirus (HPV) DNA replication: linker
      substitution analysis of the HPV type 11 origin.
AB  - Papillomavirus DNA replication requires the viral trans-acting factors E1 and E2
      in addition to the host cell's general replication machinery. The origins of DNA
      replication in bovine and human papillomavirus genomes have been localized to a
      specific part of the upstream regulatory region (URR) which includes recognition
      sites for E1 and E2 proteins. To fine map cis-acting elements influencing human
      papillomavirus type 11 (HPV-11) DNA replication and to determine the relative
      contributions of such sites, we engineered consecutive linker substitution
      mutations across a region of 158 bp in the HPV-11 origin and tested mutant
      origins for replication function in a cell-based transient replication assay. Our
      results both confirm and extend the findings of others. E2 binding sites are the
      major cis components of HPV-11 DNA replication, and there is evidence for synergy
      between these sites. Differential capacity of the three E2 binding sites within
      the origin to affect replication may be attributed, at least in part, to context.
      At least one E2 binding site is essential for replication. The imperfect AT-rich
      palindrome of the E1 helicase binding site is not essential since replication
      occurs even in the absence of this sequence. However, replication is enhanced by
      the presence of the palindromic sequence in the HPV-11 origin. Sequence
      components adjacent to the E1 and E2 binding sites, comprising AT-rich and purine
      rich elements and the consensus TATA box sequence, probably contribute to the
      overall efficiency of replication, though they are nonessential. None of the
      other cis elements of the HPV-11 origin region analyzed seems to influence
      replication significantly in the system described. The HPV-11 origin of DNA
      replication therefore differs from those of the other papovaviruses, simian virus
      40 and polyomavirus, inasmuch as an intact helicase binding site and adjacent AT
      rich components, while influential, are not absolutely essential.

PMID- 7815530
TI  - The Epstein-Barr virus LMP1 cytoplasmic carboxy terminus is essential for B
      lymphocyte transformation; fibroblast cocultivation complements a critical
      function within the terminal 155 residues.
AB  - Recombinant Epstein-Barr viruses (EBVs) were made with mutated latent membrane
      protein 1 (LMP1) genes that express only the LMP1 amino-terminal cytoplasmic and
      six transmembrane domains (MS187) or these domains and the first 44 amino acids
      of the 200-residue LMP1 carboxy-terminal domain (MS231). After infection of
      primary B lymphocytes with virus stocks having small numbers of recombinant virus
      and large numbers of P3HR-1 EBV which is transformation defective but wild type
      (WT) for LMP1, all lymphoblastoid cell lines (LCLs) that had MS187 or MS231 LMP1
      also had WT LMP1 provided by the coinfecting P3HR-1 EBV. Lytic virus infection
      was induced in these coinfected LCLs, and primary B lymphocytes were infected. In
      over 200 second-generation LCLs, MS187 LMP1 was never present without WT LMP1.
      Screening of over 600 LCLs infected with virus from MS231 recombinant virus
      infected LCLs identified two LCLs which were infected with an MS231 recombinant
      without WT LMP1. The MS231 recombinant virus could growth transform primary B
      lymphocytes when cells were grown on fibroblast feeders. Even after 6 months on
      fibroblast feeder layers, cells transformed by the MS231 recombinant virus died
      when transferred to medium without fibroblast feeder cells. These data indicate
      that the LMP1 carboxy terminus is essential for WT growth-transforming activity.
      The first 44 amino acids of the carboxy-terminal cytoplasmic domain probably
      include an essential effector of cell growth transformation, while a deletion of
      the rest of LMP1 can be complemented by growth on fibroblast feeder layers. LMP1
      residues 232 to 386 therefore provide a growth factor-like effect for the
      transformation of B lymphocytes. This effect may be indicative of the broader
      role of LMP1 in cell growth transformation.

PMID- 7815531
TI  - Mouse hepatitis virus-specific cytotoxic T lymphocytes protect from lethal
      infection without eliminating virus from the central nervous system.
AB  - Acute infection of the central nervous system by the neurotropic JHM strain of
      mouse hepatitis virus (JHMV) induces nucleocapsid protein specific cytotoxic T
      lymphocytes (CTL) not found in the periphery (S. Stohlman, S. Kyuwa, J. Polo, D.
      Brady, M. Lai, and C. Bergmann, J. Virol. 67:7050-7059, 1993). Peripheral
      induction of CTL specific for the nucleocapsid protein of JHMV by vaccination
      with recombinant vaccinia viruses was unable to provide significant protection to
      a subsequent lethal virus challenge. By contrast, the transfer of nucleoprotein
      specific CTL protected mice from a subsequent lethal challenge by reducing virus
      replication within the central nervous system, demonstrating the importance of
      the CTL response to this epitope in JHMV infection. Transfer of these CTL
      directly into the central nervous system was at least 10-fold more effective than
      peripheral transfer. Histological analysis indicated that the CTL reduced virus
      replication in ependymal cells, astrocytes, and microglia. Although the CTL were
      relatively ineffective at reducing virus replication in oligodendroglia,
      survivors showed minimal evidence of virus persistence within the central nervous
      system and no evidence of chronic ongoing demyelination.

PMID- 7815533
TI  - Translation initiation at alternate in-frame AUG codons in the rabies virus
      phosphoprotein mRNA is mediated by a ribosomal leaky scanning mechanism.
AB  - The phosphoprotein of rabies virus is a 297-amino-acid polypeptide encoded by the
      longest open reading frame of the P gene. Immunoprecipitation experiments using a
      monoclonal antiserum directed against the P protein detected the P protein and at
      least four additional shorter products in infected cells, cells transfected with
      a plasmid encoding the wild-type P protein, and purified virus (CVS strain). By
      means of deletion analyses, these proteins were shown to be translated from
      secondary downstream in-frame AUG initiation codons. Immunofluorescence
      experiments indicated that all these P products were found in the cytoplasm of
      transfected cells; however, the proteins initiated from the third, fourth, and
      fifth AUG codons were found mostly in the nucleus. Changes in the 5'-terminal
      region of the P mRNA (including site-specific mutations, deletions, and
      insertions) demonstrated that a leaky scanning mechanism is responsible for
      translation initiation of the P gene at several sites.

PMID- 7815532
TI  - Selection and analysis of human immunodeficiency virus type 1 variants with
      increased resistance to ABT-538, a novel protease inhibitor.
AB  - Inhibitors of the human immunodeficiency virus protease represent a promising new
      class of antiretroviral drugs for the treatment of AIDS. We now report the in
      vitro selection of viral variants with decreased sensitivity to a symmetry-based
      protease inhibitor, ABT-538, currently being tested in clinical trials. Molecular
      characterization of the variants shows that an isoleucine-to-valine substitution
      at position 84 results in a substantial decrease in sensitivity to the drug.
      Moreover, an additional mutation at position 82, valine to phenylalanine, further
      decreases viral susceptibility to ABT-538. Three-dimensional analysis of the
      protease-drug complex provides a structural explanation for the relative drug
      resistance induced by these two mutations. These findings emphasize the
      importance of closely monitoring patients receiving ABT-538 for the emergence of
      viral resistance and provide information that may prove useful in designing the
      next generation of protease inhibitors.

PMID- 7815534
TI  - Receptor-binding domain of murine leukemia virus envelope glycoproteins.
AB  - The surface glycoprotein (SU) of murine leukemia viruses (MuLVs) comprises two
      domains connected by a proline-rich hinge. The interaction of MuLV particles with
      subgroup-specific cell surface receptors depends primarily on two variable
      regions (VRA and VRB) located in the amino-terminal domain. To delineate the
      minimal receptor-binding domains, we examined the capacity of soluble envelope
      fragments to compete with the entry of virus particles. Amphotropic, ecotropic,
      polytropic, and xenotropic truncated SUs were produced by inserting stop codons
      in the env gene of the 4070A, Friend, MCF247 and NZB MuLVs, respectively. These
      fragments, as well as full-length envelope glycoproteins, were stably expressed
      in cells bearing the corresponding receptor. Synthesis, posttranslational
      modifications, transport, and secretion of the env gene products were monitored
      by immunoprecipitation. Cells expressing the modified SUs or naive cells
      preincubated with SU-containing conditioned media were infected with different
      pseudotypes of a retroviral vector carrying a beta-galactosidase marker gene.
      Reduction of cell susceptibility to infection in the presence of SU was used as a
      measure of receptor occupancy. The results indicated that the amphotropic and
      ecotropic envelope amino-terminal domains contain all of the determinants
      required for receptor binding. In contrast, additional sequences in the proline
      rich region were needed for efficient interaction of the polytropic and
      xenotropic amino-terminal domains with the receptors.

PMID- 7815535
TI  - Requirements for the self-directed replication of flock house virus RNA 1.
AB  - The larger segment (RNA 1) of the bipartite, positive-sense RNA genome of the
      nodavirus flock house virus encodes the viral RNA-dependent RNA polymerase. Two
      nonstructural viral proteins are made during the self-directed replication of
      this RNA: protein A (110 kDa), the translation product of RNA 1 itself, and
      protein B (11 kDa), the translation product of a subgenomic RNA (RNA 3) that is
      produced from RNA 1 during replication. To examine the roles of these proteins in
      RNA replication, specialized T7 transcription plasmids that contained wild-type
      or mutant copies of flock house virus RNA 1 cDNA were constructed and used in
      cells infected with the vaccinia virus-T7 RNA polymerase recombinant to make full
      length transcripts that directed their own replication. Sequences in the primary
      transcripts that extended beyond the ends of the authentic RNA 1 sequence
      inhibited self-directed RNA replication, but plasmids that were constructed to
      minimize these terminal extensions produced primary transcripts that replicated
      as abundantly as authentic RNA 1. Truncation or mutation of the open reading
      frame for protein A eliminated self-directed replication, although the mutant RNA
      1 remained a competent template for replication by wild-type protein A supplied
      in trans. These results showed that protein A was essential for RNA replication
      and that the process was not inseparably coupled to complete translation of the
      template. In contrast, protein B could be eliminated without inhibiting
      replication by mutations that disrupted the second of the two overlapping open
      reading frames on RNA 3. Furthermore, a mutant of RNA 1 in which the first
      nucleotide of the RNA 3 region was changed from G to U replicated at levels as
      high as those of the wild type without making either RNA 3 or protein B. However,
      diminishing replication levels were observed during subsequent replicative
      passages of RNA from both the mutants that could not make protein B. Roles for
      this protein that could account for the subtle phenotype of these mutants are
      discussed.

PMID- 7815536
TI  - The RNA polymerase PB2 subunit is not required for replication of the influenza
      virus genome but is involved in capped mRNA synthesis.
AB  - An established cell line, clone 64, in which the expression of the RNA polymerase
      PB1 and PA subunit genes and the nucleoprotein (NP) gene but not the PB2 subunit
      gene of influenza virus can be induced by the addition of dexamethasone, was used
      to analyze the replication and transcription machineries of the influenza virus.
      Both NS-CATc and NS-CATv, the chimeric nonstructural protein chloramphenicol
      acetyltransferase (NS-CAT) RNAs in the sense and antisense orientations
      positioned between the 5'- and 3'-terminal sequences of influenza virus RNA
      segment 8 (the NS gene), respectively, can be transcribed into the corresponding
      complementary-strand RNA in clone 64 cells only when treated with dexamethasone.
      Although sense-strand poly(A)+ CAT RNA was detected in the dexamethasone-treated
      clone 64 cells transfected with NS-CATv RNA, CAT activity was not detected in
      these cells and the isolated poly(A)+ CAT RNA was inert in an in vitro
      translation system. However, when the poly(A)+ CAT RNA was capped by using a
      purified yeast mRNA capping enzyme (mRNA guanylyltransferase), the capped
      poly(A)+ CAT RNA became translatable in the in vitro translation system. These
      results indicated that PB1, PA, and NP can support the replication of the
      influenza virus genome as well as the transcription to yield uncapped poly(A)+
      RNA and that PB2 is specifically required for the synthesis of capped RNA.

PMID- 7815537
TI  - Suppression of measles virus expression by noncytolytic antibody in an
      immortalized macrophage cell line.
AB  - Immune regulation of measles virus (MV) expression was studied in a persistently
      infected mouse macrophage cell line. Synthesis of both membrane-associated and
      internal MV antigens was suppressed when infected macrophages were treated with
      polyclonal rabbit anti-MV antibody that was specific for MV proteins.
      Persistently infected macrophages were treated for 3, 5, or 7 days with
      increasing doses of anti-MV antibody. All MV proteins were down-regulated 2 days
      after treatment was terminated. One week after treatment was terminated, down
      regulation was still evident but to a lesser degree. MV protein synthesis was
      suppressed whether or not complement components were inactivated by heating all
      serum supplements and antibodies. However, when complement was active, cell lysis
      accounted for some of the reduced MV protein synthesis. When lytic destruction of
      infected cells by antibody and complement was prevented by inactivation of
      complement, antibody alone reduced the cellular synthesis of viral proteins by
      noncytolytic mechanisms. The absence of cell death in the absence of complement
      was confirmed by the lack of 51Cr release from labeled cells, the lack of
      reduction in cell number, and the lack of a decrease in total protein synthesis
      when radiolabeled infected cells were treated with antibody. It is noteworthy
      that low doses of antibody were optimal for suppression in the longer-term
      experiments and did not cause lysis, even in the presence of active complement.
      Since infected macrophages disseminate virus in measles infection, noncytolytic
      regulation of these cells by antibody may supplement viral clearance by cytolytic
      T cells and other immune mechanisms.

PMID- 7815538
TI  - Neutralizing antibodies in Borna disease virus-infected rats.
AB  - Borna disease is a neurologic syndrome caused by infection with a nonsegmented,
      negative-strand RNA virus, Borna disease virus. Infected animals have antibodies
      to two soluble viral proteins, p40 and p23, and a membrane-associated viral
      glycoprotein, gp18. We examined the time course for the development of
      neutralization activity and the expression of antibodies to individual viral
      proteins in sera of infected rats. The appearance of neutralizing activity
      correlated with the development of immunoreactivity to gp18, but not p40 or p23.
      Monospecific and monoclonal antibodies to native gp18 and recombinant
      nonglycosylated gp18 were also found to have neutralizing activity and to
      immunoprecipitate viral particles or subparticles. These findings suggest that
      gp18 is likely to be present on the surface of the viral particles and is likely
      to contain epitopes important for virus neutralization.

PMID- 7815539
TI  - Multiple modifications in cis elements of the long terminal repeat of retroviral
      vectors lead to increased expression and decreased DNA methylation in embryonic
      carcinoma cells.
AB  - Infection by murine retroviruses in embryonic carcinoma (EC) and embryonic stem
      cells is highly restricted. The transcriptional unit of the Moloney murine
      leukemic virus (MoMuLV) long terminal repeat (LTR) is inactive in EC and
      embryonic stem cells in association with increased proviral methylation. In this
      study, expression in F9 EC cells was achieved from novel retroviral vectors
      containing three modifications in the MoMuLV-based retroviral vector: presence of
      the myeloproliferative sarcoma virus LTR, substitution of the primer binding
      site, and either deletion of a negative control region at the 5' end of the LTR
      or insertion of a demethylating sequence. We conclude that inhibition of
      expression from the MoMuLV LTR in EC cells is mediated through the additive
      effects of multiple cis-acting elements affecting the state of methylation of the
      provirus.

PMID- 7815540
TI  - Simian virus 40 large T antigen affects the Saccharomyces cerevisiae cell cycle
      and interacts with p34CDC28.
AB  - Simian virus 40 tumor (T) antigen, an established viral oncoprotein, causes
      alterations in cell growth control through interacting with, and altering the
      function of, cellular proteins. To examine the effects of T antigen on cell
      growth control, and to identify the cellular proteins with which it may
      functionally interact, T antigen was expressed in the budding yeast Saccharomyces
      cerevisiae. The yeast cells expressing T antigen showed morphological alterations
      as well as growth inhibition attributable, at least in part, to a lag in
      progression from G1 to S. This point in the cell cycle is also known to be
      affected by T antigen in mammalian cells. Both p34CDC28 and p34CDC2Hs were shown
      to bind to a chimeric T antigen-glutathione S-transferase fusion protein,
      indicating that T antigen interacts directly with cell cycle proteins which
      control the G1 to S transition. This interaction was confirmed by in vivo cross
      linking experiments, in which T antigen and p34CDC28 were coimmunoprecipitated
      from extracts of T-antigen-expressing yeast cells. These immunoprecipitated
      complexes could phosphorylate histone H1, indicating that kinase activity was
      retained. In addition, in autophosphorylation reactions, the complexes
      phosphorylated a novel 60-kDa protein which appeared to be underphosphorylated
      (or underrepresented) in p34CDC28-containing complexes from cells which did not
      express T antigen. These results suggest that T antigen interacts with p34CDC28
      and alters the kinase function of p34CDC28-containing complexes. These events
      correlate with alterations in the yeast cell cycle at the G1 to S transition.

PMID- 7815541
TI  - Rabies virus replication in primary murine bone marrow macrophages and in human
      and murine macrophage-like cell lines: implications for viral persistence.
AB  - To determine whether rabies viruses replicate in macrophage or macrophage-like
      cells, several human and murine macrophage-like cell lines, as well as primary
      cultures of murine bone marrow macrophages, were incubated with the Evelyn
      Rokitnicki-Abelseth (ERA) virus and several different street rabies viruses
      (SRV). ERA rabies virus replicated well in human monocytic U937 and THP-1 cells
      and murine macrophage IC-21 cells, as well as primary cultures of murine
      macrophages. Minimal replication was detected in murine monocytic WEHI-3BD- and
      PU5-1R cells, and ERA virus did not replicate in murine monocytic P388D1 or
      J774A.1 cells. A tissue culture-adapted SRV of bat origin also replicated in IC
      21 and U937 cells. Non-tissue culture-adapted SRV isolated from different animal
      species, particularly bats, replicated minimally in U937, THP-1, IC-21 cells and
      primary murine bone marrow macrophages. To determine whether rabies virus
      replication is dependent upon the state of differentiation of the macrophage-like
      cell, human promyelocytic HL-60 cells were differentiated with 12-O
      tetradecanoylphorbol-13-acetate (TPA). ERA rabies virus replicated in the
      differentiated HL-60 cells but not in undifferentiated HL-60 cells. Persistent
      infections were established in macrophage-like U937 cells with ERA rabies virus
      and SRV, and infectious SRV was isolated from adherent bone marrow cells of mice
      that had been infected 96 days previously. Virus harvested from persistently
      infected U937 cells and the adherent bone marrow cells had specifically adapted
      to each cell. This specificity was shown by the inability of the viruses to
      infect macrophages other than U937 cells and primary bone marrow macrophages,
      respectively. Virus titers of the persistently infected U937 cells fluctuated
      with extended cell passage. After 30 passages, virus released from the cells had
      lost virulence as shown by its inability to kill intracranially inoculated mice.
      However, the avirulent virus released from the persistently infected cells was
      more efficient in infecting and replicating in naive U937 cells than the virus
      which was used to establish the persistent infection. These results suggest that
      macrophages may serve as reservoirs of infection in vivo, sequestering virus
      which may subsequently be activated from its persistent state, resulting in
      clinical infection and death.

PMID- 7815542
TI  - Sequence evolution of the hypervariable region in the putative envelope region
      E2/NS1 of hepatitis C virus is correlated with specific humoral immune responses.
AB  - Sequence evolution of the hypervariable region 1 (HVR1) in the N terminus of
      E2/NS1 of hepatitis C virus (HCV) was studied retrospectively in six chimpanzees
      inoculated with the same genotype 1b strain, containing a unique predominant HVR1
      sequence. Immediately after inoculation, all animals contained the same HVR
      predominant sequence. Two animals developed an acute self-limiting infection.
      Anti-HVR1 immunoglobulin G (IgG) was produced 40 to 60 days after inoculation and
      rapidly disappeared after normalization of transaminases. Another chimpanzee,
      previously infected with human immunodeficiency virus type 1, showed a delayed
      response to HVR1 epitopes after superinfection with HCV. No sequence variation of
      HVR1 was observed in these two animals during the transient viremia in the acute
      phase. Three other chimpanzees developed a chronic HCV infection. During follow
      up, sequence evolution occurred in two animals and their anti-HVR1 response
      remained at varying but detectable levels. The first mutations occurred
      immediately after the production of anti-HVR1 during the acute phase. However,
      IgM anti-HVR1 was not detectable. Remarkably, HVR1 sequences remained conserved
      for more than 6 years in another chronically infected animal. This correlated
      with the complete absence of detectable anti-HVR1 during this period. Seven years
      after inoculation, anti-HVR1 IgG was produced and coincided with an HVR1
      alteration. These results strongly suggest the involvement of neutralizing anti
      HVR antibodies in sequence evolution of HVR1 through immune selection.

PMID- 7815543
TI  - HPRS-103 (exogenous avian leukosis virus, subgroup J) has an env gene related to
      those of endogenous elements EAV-0 and E51 and an E element found previously only
      in sarcoma viruses.
AB  - The avian leukosis and sarcoma virus (ALSV) group comprises eight subgroups based
      on envelope properties. HPRS-103, an exogenous retrovirus recently isolated from
      meat-type chicken lines, is similar to the viruses of these subgroups in group
      antigen but differs from them in envelope properties and has been assigned to a
      new subgroup, J. HPRS-103 has a wide host range in birds, and unlike other
      nontransforming ALSVs which cause late-onset B-cell lymphomas, HPRS-103 causes
      late-onset myelocytomas. Analysis of the sequence of an infectious clone of the
      complete proviral genome indicates that HPRS-103 is a multiple recombinant of at
      least five ALSV sequences and one EAV (endogenous avian retroviral) sequence. The
      HPRS-103 env is most closely related to the env gene of the defective EAV-E51 but
      divergent from those of other ALSV subgroups. Probing of restriction digests of
      line 0 chicken genomic DNA has identified a novel group of endogenous sequences
      (EAV-HP) homologous to that of the HPRS-103 env gene but different from sequences
      homologous to EAV and E51. Unlike other replication-competent nontransforming
      ALSVs, HPRS-103 has an E element in its 3' noncoding region, as found in many
      transforming ALSVs. A deletion found in the HPRS-103 U3 EFII enhancer factor
      binding site is also found in all replication-defective transforming ALSVs
      (including MC29, which causes rapid-onset myelocytomas).

PMID- 7815544
TI  - A novel translational regulation function for the simian virus 40 large-T antigen
      gene.
AB  - Cells use the interferon-induced, double-stranded-RNA-dependent protein kinase
      PKR as a defense against virus infections. Upon activation, PKR phosphorylates
      and thereby inactivates the protein synthesis initiation factor eIF-2, resulting
      in the cessation of protein synthesis. Viruses have evolved various strategies to
      counteract this cellular defense. In this paper, we show that simian virus 40
      (SV40) large-T antigen can antagonize the translational inhibitory effect
      resulting from the activation of PKR in virus-infected cells. Unlike the
      situation with other virus-host cell interactions, SV40 large-T antigen does not
      block the activation of PKR, suggesting that SV40 counteracts the cellular
      antiviral response mediated by PKR at a step downstream of PKR activation.
      Mutational analysis of large-T antigen indicates that a domain located between
      amino acids 400 and 600 of large-T antigen is responsible for this function.
      These results define a novel translational regulatory function for the SV40 large
      T antigen.

PMID- 7815545
TI  - A three-nucleotide deletion in the UL97 open reading frame is responsible for the
      ganciclovir resistance of a human cytomegalovirus clinical isolate.
AB  - Multiple human cytomegalovirus (HCMV) strains frequently coexist in patients with
      AIDS, and chronic ganciclovir treatment may favor the emergence of ganciclovir
      resistant viral mutants. We report the molecular and biochemical characterization
      of a HCMV ganciclovir-resistant strain (VR3480) previously recovered from a
      patient with AIDS who was undergoing multiple courses of ganciclovir treatment
      (G. Gerna, F. Baldanti, M. Zavattoni, A. Sarasini, E. Percivalle, and M. G.
      Revello, Antiviral Res. 19:333-345, 1992). Ganciclovir resistance of strain
      VR3480 was related to impaired ability to monophosphorylate the drug, as
      indicated by the finding that ganciclovir phosphorylation values for VR3480 were
      30% of those shown by the HCMV reference strain AD169 in an in vitro activity
      assay. Sequencing of the UL97 gene of VR3480, which encodes the viral kinase
      responsible for ganciclovir phosphorylation, showed an in-frame deletion of three
      nucleotides resulting in the loss of a leucine at position 595 in the
      polypeptide. Mutant VR3480 UL97 DNA was able to transfer resistance to the AD169
      strain in marker rescue experiments. Analysis of virus isolates and blood
      polymorphonuclear leukocyte samples spanning the 2-year follow-up period of the
      patient showed that ganciclovir-resistant strain VR3480 arose ex novo during
      prolonged antiviral treatment and accounted for the majority of virus load
      circulating in blood during the period of clinical resistance to ganciclovir
      treatment.

PMID- 7815546
TI  - Human foamy virus Bel1 transactivator contains a bipartite nuclear localization
      determinant which is sensitive to protein context and triple multimerization
      domains.
AB  - The Bel1 protein of human foamy virus is a 300-amino-acid nuclear regulatory
      protein which transactivates the gene expression directed by the homologous long
      terminal repeat and the human immunodeficiency virus type 1 long terminal repeat.
      While previous reports suggested that the single basic domain of Bel1 from
      residues 211 to 222 and/or 209 to 226 is necessary and sufficient for efficient
      nuclear localization (L. K. Venkatesh, C. Yang, P. A. Theodorakis, and G.
      Chinnandurai, J. Virol. 67:161-169, 1993; F. He, J. D. Sun, E. D. Garrett, and B.
      R. Cullen, J. Virol. 67:1896-1904, 1993), our recent data showed that another
      basic domain, from amino acid residues 199 to 200, is also required for nuclear
      localization of Bel1 (C. W. Lee, C. Jun, K. J. Lee, and Y. C. Sung, J. Virol.
      68:2708-2719, 1994). To clarify this discrepancy, we constructed various bel1
      lacZ chimeric constructs and several linker insertion mutants and determined
      their subcellular localization. When the region of Bel1 containing basic domains
      was placed at an internal site of the lacZ gene, the nuclear localization signal
      (NLS) of Bel1 consisted of two discontinuous basic regions separated by an
      intervening sequence. Moreover, insertion of specific amino acids between two
      basic regions disrupted the activity of the Bel1 NLS. On the other hand, Bel1
      residues 199 and 200 were not required to direct the Bel1-beta-galactosidase
      chimeric protein to the nucleus when the Bel1 NLS was appended to the amino
      terminus of beta-galactosidase. These results indicate that the function of the
      Bel1 NLS is sensitive to the protein context within which the sequence is
      present. In addition, we demonstrated that the Bel1 protein forms a multimeric
      complex in the nuclei of mammalian cells by using a sensitive in vivo protein
      protein interaction assay. Mutational analyses revealed that the regions which
      mediate multimer formation map to three domains of Bel1, i.e., residues 1 to 31,
      42 to 82, and 82 to 111. Furthermore, our results show that the region of Bel1
      from residues 202 to 226 prevents Bel1 from forming a multimeric complex.

PMID- 7815547
TI  - Identification of the murine coronavirus p28 cleavage site.
AB  - Mouse hepatitis virus strain A59 encodes a papain-like cysteine proteinase (PLP
      1) that, during translation of ORF1a, cleaves p28 from the amino terminus of the
      growing polypeptide chain. In order to determine the amino acid sequences
      surrounding the p28 cleavage site, the first 4.6 kb of murine hepatitis virus
      strain A59 ORF1a was expressed in a cell-free transcription-translation system.
      Amino-terminal radiosequencing of the resulting downstream cleavage product
      demonstrated that cleavage occurs between Gly-247 and Val-248. Site-directed
      mutagenesis of amino acids surrounding the p28 cleavage site revealed that
      substitutions of Arg-246 (P2) and Gly-247 (P1) nearly eliminated cleavage of p28.
      Single-amino-acid substitutions of other residues between P7 and P2' were
      generally permissive for cleavage, although a few changes did greatly reduce
      proteolysis. The relationship between the p28 cleavage site and other viral and
      cellular papain proteinase cleavage sites is discussed.

PMID- 7815548
TI  - Mode of action of SDZ NIM 811, a nonimmunosuppressive cyclosporin A analog with
      activity against human immunodeficiency virus type 1 (HIV-1): interference with
      early and late events in HIV-1 replication.
AB  - SDZ NIM 811 is a cyclosporin A analog that is completely devoid of
      immunosuppressive capacity but exhibits potent and selective anti-human
      immunodeficiency virus type 1 (HIV-1) activity. The mechanism of action of SDZ
      NIM 811 is clearly different from those of all other anti-HIV agents described so
      far. In cell-free assays, it is not an inhibitor of reverse transcriptase,
      protease, integrase, and it does not interfere with Rev or Tat function. SDZ NIM
      811 does not down-regulate CD4 or inhibit fusion between infected and uninfected,
      CD4-expressing cells. p24 production from chronically HIV-infected cells is not
      impaired either. To elucidate the mode of action of SDZ NIM 811, we performed DNA
      PCR analysis in HIV-1 IIIB-infected MT4 cells in one cycle of virus replication.
      The effects of SDZ NIM 811 on the kinetics of viral DNA synthesis, appearance of
      two-long terminal repeat circles (2-LTR circles), and integration of DNA were
      studied. SDZ NIM 811 inhibited 2-LTR circle formation in a concentration
      dependent manner, which is indicative of nuclear localization of preintegration
      complexes. Half-maximal inhibition was achieved at 0.17 microgram/ml; this
      concentration is close to the 50% inhibitory concentrations (0.01 to 0.2
      microgram/ml) for viral growth inhibition. As expected, integration of proviral
      DNA into cellular DNA was also inhibited by SDZ NIM 811. Analysis of the viral
      particles produced by SDZ NIM 811-treated, chronically infected cells revealed
      amounts of capsid proteins, reverse transcriptase activity, and viral RNA
      comparable to those of the untreated control. However, these particles showed a
      dose-dependent reduction in infectivity (50% inhibitory concentration of 0.028
      microgram/ml) which indicates that the assembly process is also impaired by SDZ
      NIM 811. Gag proteins are postulated to play a role not only in assembly but also
      in early steps of viral replication, e.g., nuclear localization of the
      preintegration complex. Recently, it was reported that HIV-1 Gag protein binds to
      cyclophilin A, the intracellular receptor for cyclosporin A. Interference with
      Gag-cyclophilin interaction may be the molecular basis for the antiviral activity
      of cyclosporin A and its analogs.

PMID- 7815549
TI  - The herpes simplex virus 1 UL11 proteins are associated with cytoplasmic and
      nuclear membranes and with nuclear bodies of infected cells.
AB  - Earlier studies have shown that the UL11 gene of herpes simplex virus encodes a
      myristylated virion protein and that the UL11 gene enables efficient virion
      envelopment and export from infected cells. A rabbit polyclonal antibody directed
      against an affinity-purified UL11-glutathione-S-transferase fusion protein was
      made and used to study the properties of the UL11 protein and its distribution in
      infected cells. We report the following: (i) UL11 protein formed up to five bands
      (apparent M(r)s, 17,000 to 22,000) in denaturing polyacrylamide gels; (ii)
      fluorescent-antibody studies revealed the presence of UL11 protein in the
      perinuclear space and in sites within the nucleus; (iii) immune electron
      microscopic studies indicated that the UL11 gene products were associated with
      the inner nuclear membrane, with cytoplasmic membranes and ribbon-like
      cytoplasmic structures resembling membranous organelles, with nuclear bodies
      shown by fluorescence microscopy to be different from nucleoli in which US11
      protein accumulates, and with enveloped virions but not with nuclear capsids; and
      (iv) the nuclear bodies containing UL11 protein were reminiscent both of type IV
      morphotypes consisting of an electron-dense core containing the UL11 proteins
      surrounded by a more electron-transluscent core and of type V morphotypes
      consisting of material homogenous in electron opacity. We conclude that (i) the
      UL11 protein is processed after synthesis; (ii) the localization of UL11 protein
      with virions and membranes is consistent with the hypothesis that UL11 plays a
      role in the transport of virions to the extracellular space; and (iii) although
      the significance of the association of UL11 proteins with nuclear bodies is
      unknown, the results indicate that nuclear bodies differ with respect to their
      morphologies and contents of viral protein and suggest that UL11 protein may have
      more than one function in the infected cell.

PMID- 7815550
TI  - A heterologous heparin-binding domain can promote functional attachment of a
      pseudorabies virus gC mutant to cell surfaces.
AB  - The efficient attachment of pseudorabies virus to cultured cells is dependent on
      an electrostatic interaction between negatively charged cell surface heparan
      sulfate and the viral envelope glycoprotein gC. Deletion of the first one-third
      of gC severely impairs virus attachment, but the mutant virions are still capable
      of entering cells and establishing an infection via a gC-independent pathway.
      This region of gC contains three clusters of positively charged amino acids that
      exactly or nearly conform to proposed consensus motifs for heparin-binding
      domains (HBDs), and the loss of one or more of these potential HBDs may be
      responsible for the observed attachment defect. To more directly show the
      involvement of HBDs in pseudorabies virus attachment to cells, we replaced the
      first one-third of gC with a single, biochemically defined HBD from
      apolipoprotein B-100. On the basis of the results of attachment, penetration, and
      heparin competition assays, the heterologous HBD mediated heparan sulfate
      dependent virus attachment, but not to fully wild-type levels. Although the
      intermediate phenotype is not understood, the apolipoprotein B-100 HBD may
      represent the smallest defined amino acid sequence that promotes functional
      herpesvirus attachment to cultured cells.

PMID- 7815551
TI  - Fibronectin of human liver sinusoids binds hepatitis B virus: identification by
      an anti-idiotypic antibody bearing the internal image of the pre-S2 domain.
AB  - Anti-idiotypic antibodies (anti-Ids) have been successfully used to characterize
      and isolate receptors of several cell ligands. To prepare an immunological probe
      for identification of cellular components interacting with the hepatitis B virus
      (HBV), polyclonal antisera against a panel of five HBV-specific monoclonal
      antibodies (MAbs) were produced in syngeneic BALB/c mice. MAbs to HBV used for
      immunization (Ab1) recognized biologically important and potentially neutralizing
      epitopes, located in the pre-S1, pre-S2, or S region-encoded domains of HBV
      proteins. All the anti-Ids (Ab2) were specific to idiotopes of the homologous Ab1
      and inhibited their interaction with the corresponding viral epitopes, suggesting
      that they recognized unique determinants on the paratope of each immunizing Ab1.
      Therefore, all five generated polyclonal anti-Ids were of the Ab2 beta type and
      could represent internal images of viral epitopes. Ab2 raised against the pre-S2
      region-specific MAb F124 bound to the extracellular matrix fibronectin of human
      liver sinusoids. Immunohistochemical studies demonstrated the attachment of viral
      and recombinant (S, M) hepatitis B surface antigen particles with the pre-S2
      region-encoded epitopes to the fibronectin of human liver sinusoids. In contrast,
      recombinant (S, L*) hepatitis B surface antigen particles, in which the epitope
      recognized by F124 MAb was not expressed, did not show any binding capacity.
      These findings suggest that human liver fibronectin may bind HBV in vivo by the
      pre-S2 region-encoded epitopes in a species-restricted manner. Furthermore,
      binding of the circulating virus to liver sinusoids could facilitate its
      subsequent uptake by hepatocytes.

PMID- 7815552
TI  - An N-terminal domain of the Sendai paramyxovirus P protein acts as a chaperone
      for the NP protein during the nascent chain assembly step of genome replication.
AB  - Two domains involved in RNA synthesis have recently been found within the N
      terminal 77 amino acids of the Sendai virus P protein. One domain is required for
      RNA synthesis per se and has properties in common with the transactivation
      domains of cellular transcription factors. The second domain is thought to be
      specifically required for the nascent chain assembly step in genome replication.
      We have further mapped this second domain by the construction of chimeric and
      deleted P proteins to amino acids 33 to 41 of P and by examining the abilities of
      these P proteins to support DI genome replication in vivo. Using glycerol
      gradient sedimentation, we have shown that this domain is required to form a
      stable complex with unassembled NP (P-NP0) and to prevent NP from assembling
      illegitimately, i.e., independently of the concurrent assembly of a nascent viral
      genome. Since the P-NP0 complex represents the functional form of unassembled NP
      which is delivered to the nascent chain during genome replication, and since
      amino acids 33 to 41 are not required for the stable interaction of P with the
      assembled NP of the nucleocapsid, this chaperone function of P is not required
      for mRNA synthesis or the RNA synthesis step of genome replication.

PMID- 7815554
TI  - Attenuation of Theiler's murine encephalomyelitis virus by modifications of the
      oligopyrimidine/AUG tandem, a host-dependent translational cis element.
AB  - A set of Theiler's murine encephalomyelitis virus mutants with engineered
      alterations in the conserved oligopyrimidine/AUG tandem (E. V. Pilipenko, A. P.
      Gmyl, S. V. Maslova, G. A. Belov, A. N. Sinyakov, M. Huang, T. D. K. Brown, and
      V. I. Agol, J. Mol. Biol. 241:398-414, 1994) were assayed for their growth
      potential in BHK-21 cells (as reflected in plaque size) and for neurovirulence
      upon intracerebral inoculation of mice. Tandem-destroying mutations, which
      included substitutions in the oligopyrimidine moiety and extended insertions into
      the oligopyrimidine/AUG spacer, exerted relatively little effect on the plaque
      size but ensured a high level of attenuation. The attenuated mutants exhibited
      remarkable genetic stability upon growth in BHK-21 cells. However, the brains of
      rare animals that developed symptoms after the inoculation with high doses of
      these mutants invariably contained pseudorevertants with the oligopyrimidine/AUG
      tandem restored by diverse deletions or an AUG-generating point mutation. The AUG
      moiety of the tandem in the revertant genomes was represented by either a cryptic
      codon or initiator codon. The results demonstrate that the tandem, while
      dispensable for the Theiler's murine encephalomyelitis virus growth in BHK-21
      cells, is essential for neurovirulence in mice. Thus, the oligopyrimidine/AUG
      tandem is a host-dependent cis-acting control element that may be essential for
      virus replication under certain conditions. The functional activity of the tandem
      was retained when its oligopyrimidine or AUG moieties were made double stranded.
      A possible role of the tandem in the cap-independent internal initiation of
      translation on the picornavirus RNA templates is discussed.

PMID- 7815553
TI  - Deletions in one domain of the Friend virus-encoded membrane glycoprotein
      overcome host range restrictions for erythroleukemia.
AB  - Although the Friend virus-encoded membrane glycoprotein (gp55) activates
      erythropoietin receptors (EpoR) to cause erythroblastosis only in certain inbred
      strains of mice but not in other species, mutant viruses can overcome aspects of
      mouse resistance. Thus, mice homozygous for the resistance allele of the Fv-2
      gene are unaffected by gp55 but are susceptible to mutant glycoproteins that have
      partial deletions in their ecotropic domains. These and other results have
      suggested that proteins coded for by polymorphic Fv-2 alleles might directly or
      indirectly interact with EpoR and that changes in gp55 can overcome this defense.
      A new viral mutant with an exceptionally large deletion in its ecotropic domain
      is now also shown to overcome Fv-2rr resistance. In all cases, the glycoproteins
      that activate EpoR are processed to cell surfaces as disulfide-bonded dimers. To
      initiate analysis of nonmurine resistances, we expressed human EpoR and mouse
      EpoR in the interleukin 3-dependent mouse cell line BaF3 and compared the
      abilities of Friend virus-encoded glycoproteins to convert these cells to growth
      factor independence. Human EpoR was activated in these cells by erythropoietin
      but was resistant to gp55. However, human EpoR was efficiently activated in these
      cells by the same viral mutants that overcome Fv-2rr resistance in mice. By
      construction and analysis of human-mouse EpoR chimeras, we obtained evidence that
      the cytosolic domain of human EpoR contributes to its resistance to gp55 and that
      this resistance is mediated by accessory cellular factors. Aspects of host
      resistance in both murine and nonmurine species are targeted specifically against
      the ecotropic domain of gp55.

PMID- 7815555
TI  - Characterization of the CD48 gene demonstrates a positive element that is
      specific to Epstein-Barr virus-immortalized B-cell lines and contains an
      essential NF-kappa B site.
AB  - Epstein-Barr virus (EBV) infection of mature, resting B cells drives them to
      become lymphoblasts expressing high levels of cell surface molecules, such as
      CD48, characteristically expressed on normal activated B cells. Here, we report
      on the identification of an enhancer element in the CD48 gene which reproducibly
      confers strong transcriptional activity only in EBV-positive B-lymphoblastoid
      cell lines. The element is not activated upon infection of established EBV
      negative B-cell lines, indicating that EBV fails to drive these cells to a fully
      lymphoblastoid phenotype. An NF-kappa B binding site is an essential component of
      the element but alone is not sufficient to account for the activity or the
      specificity of the element. We have detected a specific nuclear protein complex
      that binds to the element and show that NF-kappa B1 (p50) is a part of this
      complex. The EBV-encoded latent membrane protein 1 is capable of transactivating
      the isolated CD48 NF-kappa B site but not the intact element, suggesting that the
      latent membrane protein 1-driven activation of NF-kappa B/Rel must interact with
      other regulatory pathways to control expression of cellular genes as EBV drives
      resting B cells into the cell cycle.

PMID- 7815556
TI  - The human immunodeficiency virus type 1 vpr gene prevents cell proliferation
      during chronic infection.
AB  - Human immunodeficiency virus type 1 (HIV-1) is a retrovirus that can cause
      extensive cytopathicity in T cells. However, long-term productive infection of T
      cell lines has been described. Here we show that although Vpr has no effect on
      the initial cytopathic effect of HIV-1, viruses that contain an intact vpr gene
      are unable to establish a chronic infection of T cells. However, virus with a
      mutated vpr gene can readily establish such long-term cultures. The effect of Vpr
      is independent of the env gene and the nef gene. Furthermore, expression of Vpr
      alone affects the progression of cells in the cell cycle. These results suggest
      that HIV-1 has evolved a viral gene to prevent chronic infection of T cells.

PMID- 7815557
TI  - Interaction of mouse hepatitis virus (MHV) spike glycoprotein with receptor
      glycoprotein MHVR is required for infection with an MHV strain that expresses the
      hemagglutinin-esterase glycoprotein.
AB  - In addition to the spike (S) glycoprotein that binds to carcinoembryonic antigen
      related receptors on the host cell membrane, some strains of mouse coronavirus
      (mouse hepatitis virus [MHV]) express a hemagglutinin esterase (HE) glycoprotein
      with hemagglutinating and acetylesterase activity. Virions of strains that do not
      express HE, such as MHV-A59, can infect mouse fibroblasts in vitro, showing that
      the HE glycoprotein is not required for infection of these cells. The present
      work was done to study whether interaction of the HE glycoprotein with
      carbohydrate moieties could lead to virus entry and infection in the absence of
      interaction of the S glycoprotein with its receptor glycoprotein, MHVR. The DVIM
      strain of MHV expresses large amounts of HE glycoprotein, as shown by
      hemadsorption, acetylesterase activity, and immunoreactivity with antibodies
      directed against the HE glycoprotein of bovine coronavirus. A monoclonal anti
      MHVR antibody, MAb-CC1, blocks binding of virus S glycoprotein to MHVR and blocks
      infection of MHV strains that do not express HE. MAb-CC1 also prevented MHV-DVIM
      infection of mouse DBT cells and primary mouse glial cell cultures. Although MDCK
      I cells express O-acetylated sialic acid residues on their plasma membranes,
      these canine cells were resistant to infection with MHV-A59 and MHV-DVIM.
      Transfection of MDCK-I cells with MHVR cDNA made them susceptible to infection
      with MHV-A59 and MHV-DVIM. Thus, the HE glycoprotein of an MHV strain did not
      lead to infection of cultured murine neural cells or of nonmurine cells that
      express the carbohydrate ligand of the HE glycoprotein. Therefore, interaction of
      the spike glycoprotein of MHV with its carcinoembryonic antigen-related receptor
      glycoprotein is required for infectivity of MHV strains whether or not they
      express the HE glycoprotein.

PMID- 7815558
TI  - Immunopathogenic role of T-cell subsets in Borna disease virus-induced
      progressive encephalitis.
AB  - Borna disease is an immunopathological virus-induced encephalopathy comprising
      severe inflammation and degenerative brain cell lesions which results in organ
      atrophy and chronic debility in rats. CD4+ and CD8+ T cells have been reported to
      be involved in the development of this disease of the central nervous system. A
      virus-specific homogeneous T-cell line, established in vitro after immunization
      of rats with the recombinant 24-kDa virus-specific protein, showed antigen
      specific proliferation in the presence of the 24-kDa but not the 38-kDa Borna
      disease virus-specific protein, another major virus-specific antigen. This T-cell
      line, P205, was found to exhibit characteristics of a T-helper cell: CD4+ CD8- IL
      2- IL-4- IFN-gamma+ IL-6+ IL-10+. Furthermore, this T-cell line expressed the
      alpha/beta T-cell receptor and the alpha 4 integrin (VLA-4). Adoptive transfer of
      this helper cell resulted in an increase of antibody titers and two different
      types of disease in virus-infected rats after cyclophosphamide-induced
      immunosuppression. (i) Rats receiving T cells between 10 and 18 days after
      treatment with cyclophosphamide showed an acute lymphoproliferative disease in
      the gut and lungs within 9 days after adoptive transfer and died. (ii) Passive
      transfer within the first 5 days after immunosuppressive treatment resulted in
      typical Borna disease associated with neurological symptoms such as ataxia and
      paresis starting 14 to 16 days after transfer. Immunohistological analysis of the
      brains of rats with Borna disease uniformly revealed the presence of CD8+ T cells
      in encephalitic lesions in addition to CD4+ cells that were found in the brains
      of recipients of the virus-specific CD4+ T-cell line, irrespective of whether
      neurological symptoms developed or not. However, recipient rats treated with
      antibodies against CD8+ T cells developed neither encephalitis nor disease.
      Therefore, CD4+ T cells appear to accumulate in the brain and cause perivascular
      inflammatory lesions which alone obviously do not cause disease. In contrast, the
      presence of CD8+ cells apparently directly correlates with the development of
      neurological symptoms.

PMID- 7815559
TI  - The T-cell-independent role of gamma interferon and tumor necrosis factor alpha
      in macrophage activation during murine cytomegalovirus and herpes simplex virus
      infections.
AB  - We defined the normal and innate (without functional B or T cells) inflammatory
      response to infection with mouse cytomegalovirus (MCMV) or herpes simplex virus
      (HSV). Intraperitoneal infection with MCMV or HSV induced an inflammatory
      infiltrate consisting largely of macrophages (M phi) in both normal CB17 and
      severe combined immunodeficient (SCID) mice (lacking functional B or T cells). M
      phi from infected mice were activated as shown by (i) spread morphology, (ii)
      increased expression of major histocompatibility complex (MHC) class II, MHC
      class I, and intercellular adhesion molecule-1 molecules, and (iii)
      downregulation of M phi-specific cell surface protein F4/80. In vivo
      administration of neutralizing antibodies specific for gamma interferon (IFN
      gamma) or tumor necrosis factor alpha (TNF alpha) inhibited MHC class II
      induction on infiltrating M phi in both normal and CB17 SCID mice. Anti-TNF alpha
      decreased the number of M phi in virus-induced inflammatory exudates. The MCMV
      titer increased in the spleen and liver of IFN gamma-depleted SCID mice, while
      TNF alpha depletion increased only splenic titers. MCMV-induced pathology was
      also increased in spleens of IFN gamma- and TNF alpha-depleted SCID mice. We
      conclude that (i) M phi activation is a prominent part of inflammatory responses
      to herpesvirus infection and (ii) IFN gamma and TNF alpha play a critical role in
      both virus-induced M phi activation and control of herpesvirus growth independent
      of T and B cells. This suggests that IFN gamma- and TNF alpha-mediated M phi
      activation is an important aspect of innate immunity to viral infection. As the M
      phi may be involved in MCMV latency, IFN gamma- and TNF alpha-dependent M phi
      activation during primary infection may be relevant to establishment of viral
      latency.

PMID- 7815560
TI  - Role of cucumovirus capsid protein in long-distance movement within the infected
      plant.
AB  - Direct evidence is presented for a host-specific role of the cucumovirus capsid
      protein in long-distance movement within infected plants. Cucumber (Cucumis
      sativus L.) is a systemic host for cucumber mosaic cucumovirus (CMV). Tomato
      aspermy cucumovirus, strain 1 (1-TAV), multiplied to the levels of CMV (i.e.,
      replicated, moved from cell to cell, and formed infectious particles) in the
      inoculated leaves of cucumbers but was completely unable to spread systemically.
      The defective long-distance systemic movement of 1-TAV was complemented by CMV in
      mixed infections. Coinfection of cucumbers with 1-TAV RNA with various
      combinations of transcripts from full-length cDNA clones of CMV genomic RNA 1,
      RNA2, and RNA3 showed that CMV RNA3 alone complemented 1-TAV long-distance
      movement. We obtained mutants containing mutations in the two open reading frames
      in CMV RNA3 encoding the 3a protein and the capsid protein (CP), both of which
      are necessary for cell-to-cell movement of CMV. Complementation experiments with
      mutant CMV RNA3 showed that only 3a protein mutants, i.e., those with an intact
      CP, complemented the long-distance movement of 1-TAV in cucumbers. Since CMV and
      TAV have common systemic host plants, the results presented here are strong
      evidence for an active, host-specific function of the CPs of these two
      cucumoviruses for long-distance spread in the phloem. The results also suggest
      that the plasmodesmata in the vascular system and/or at the boundary between the
      mesophyll and the vascular system, involved in long-distance movement through the
      phloem, and those in the mesophyll, involved in cell-to-cell movement, differ
      functionally.

PMID- 7815561
TI  - Simian virus 40 large T antigen contains two independent activities that
      cooperate with a ras oncogene to transform rat embryo fibroblasts.
AB  - The simian virus 40 large T antigen immortalizes growing primary cells in
      culture. In addition, this viral oncoprotein cooperates with an activated ras
      protein to produce dense foci on monolayers of rat embryo fibroblasts (REF). The
      relationship between independent immortalization and cooperative transformation
      with ras has not been defined. Previously, two regions of T antigen were shown to
      contain immortalization activities. An N-terminal fragment consisting of amino
      acids 1 to 147 immortalizes rodent cells (L. Sompayrac and K. J. Danna, Virology
      181:412-415, 1991). Loss-of-function analysis indicated that immortalization
      depended on integrity of the T-antigen segments containing amino acids 351 to 450
      and 533 to 626 (T. D. Kierstead and M. J. Tevethia, J. Virol. 67:1817-1829,
      1993). The experiments described here were directed toward determining whether
      these same T-antigen regions were sufficient for cooperation with ras. Initially,
      constructs that produce T antigens containing amino acids 176 to 708 (T176-708)
      or 1 to 147 were tested in a ras cooperation assay. Both polypeptides cooperated
      with ras to produce dense foci on monolayers of primary REF. These results showed
      that T antigen contains two separate ras cooperation activities. In order to
      determine the N-terminal limit of the ras cooperation activity contained within
      the T176-708 polypeptide, a series of constructs designed to produce fusion
      proteins containing T-antigen segments beginning at residues 251, 301, 337, 351,
      371, 401, 451, 501, 551, 601, and 651 was generated. Each of these constructs was
      tested for the capacity to cooperate with ras to produce dense foci on REF
      monolayers. The results indicated that a polypeptide containing T-antigen amino
      acids 251 to 708 (T251-708) was sufficient to cooperate with ras, whereas the
      more extensively truncated products were not. The abilities of the N-terminally
      truncated T antigens to bind p53 were examined in p53-deficient cells infected
      with a recombinant vaccinia virus expressing a phenotypically wild-type mouse
      p53. The results showed that polypeptides containing T-antigen amino acids 251 to
      708, 301 to 708, 337 to 708, or 351 to 708 retained p53-binding capacity. The
      introduction into the T251-708 polypeptide of deletions that either prevented p53
      binding (dl434-444) or did not prevent p53 binding (dl400) abrogated ras
      cooperation. These results indicated that although p53 binding may be necessary
      for ras cooperation, an additional, as-yet-undefined activity contained within
      the T251-708 polypeptide is needed.

PMID- 7815562
TI  - Papillomavirus capsid binding and uptake by cells from different tissues and
      species.
AB  - The inability of papillomaviruses (PV) to replicate in tissue culture cells has
      hampered the study of the PV life cycle. We investigated virus-cell interactions
      by the following two methods: (i) using purified bovine PV virions or human PV
      type 11 (HPV type 11) virus-like particles (VLP) to test the binding to
      eukaryotic cells and (ii) using different VLP-reporter plasmid complexes of
      HPV6b, HPV11 L1 or HPV11 L1/L2, and HPV16 L1 or HPV16 L1/L2 to study uptake of
      particles into different cell lines. Our studies showed that PV capsids bind to a
      broad range of cells in culture in a dose-dependent manner. Binding of PV capsids
      to cells can be blocked by pretreating the cells with the protease trypsin.
      Penetration of PV into cells was monitored by using complexes in which the
      purified PV capsids were physically linked to DNA containing the gene for beta
      galactosidase driven by the human cytomegalovirus promoter. Expression of beta
      galactosidase occurred in < 1% of the cells, and the efficiency of PV receptor
      mediated gene delivery was greatly enhanced (up to 10 to 20% positive cells) by
      the use of a replication-defective adenovirus which promotes endosomal lysis. The
      data generated by this approach further confirmed the results obtained from the
      binding assays, showing that PV enter a wide range of cells and that these cells
      have all functions required for the uptake of PV. Binding and uptake of PV
      particles can be blocked by PV-specific antisera, and different PV particles
      compete for particle uptake. Our results suggest that the PV receptor is a
      conserved cell surface molecule(s) used by different PV and that the tropism of
      infection by different PV is controlled by events downstream of the initial
      binding and uptake.

PMID- 7815563
TI  - Induction of AIDS by simian immunodeficiency virus from an African green monkey:
      species-specific variation in pathogenicity correlates with the extent of in vivo
      replication.
AB  - Previous studies suggested that simian immunodeficiency viruses isolated from
      African green monkeys (SIVagm) are relatively nonpathogenic. The report describes
      the isolation and biologic and molecular characterization of a pathogenic SIVagm
      strain derived from a naturally infected African green monkey. This virus induced
      an AIDS-like syndrome characterized by early viremia, frequent thrombocytopenia,
      severe lymphoid depletion, opportunistic infections, meningoencephalitis, and
      death of five of eight macaques within 1 year after infection. An infectious
      clone derived from this isolate reproduced the immunodeficiency disease in pig
      tailed (PT) macaques, providing definitive proof of the etiology of this
      syndrome. Although the virus was highly pathogenic in PT macaques, no disease was
      observed in experimentally infected rhesus macaques and African green monkeys
      despite reproducible infection of the last two species. Whereas infection of PT
      macaques was associated with a high viral load in plasma, peripheral blood
      mononuclear cells, and tissues, low-level viremia and infrequent expression in
      lymph nodes of rhesus macaques and African green monkeys suggest that differences
      in pathogenicity are associated with the extent of in vivo replication. The
      availability of a pathogenic molecular clone will provide a useful model for the
      study of viral and host factors that influence pathogenicity.

PMID- 7815564
TI  - Eighteen baculovirus genes, including lef-11, p35, 39K, and p47, support late
      gene expression.
AB  - We report the identification of four additional genes of the Autographa
      californica nuclear polyhedrosis virus involved in expression from a late
      baculovirus promoter in transient expression assays. Three of these genes, p35,
      39K, and p47, have been previously described. The role of the p35 gene product in
      late gene expression may be related to its ability to block apoptosis, since two
      other baculovirus genes also known to block apoptosis, Cp-iap and Op-iap, were
      able to functionally replace p35 in the transient expression assay. The
      requirement for p47 in this assay confirms its role in late gene expression, a
      role previously established by characterization of a temperature-sensitive mutant
      of p47, while the requirement for 39K may be related to its known association
      with the virogenic stroma. The fourth gene identified as a late expression factor
      gene, lef-11, was located immediately upstream of 39K and is predicted to encode
      a 13-kDa polypeptide. When plasmids containing these 4 genes were cotransfected
      with plasmids containing the 14 genes previously identified as late gene
      expression factors, the level of expression from the late capsid promoter was
      similar to that observed for a library of clones representing the entire viral
      genome. The genes provided by these 18 plasmids thus represent the viral genes
      necessary and sufficient to support expression from a late viral promoter in this
      transient expression assay.

PMID- 7815566
TI  - Reducing the complexity of the transforming Epstein-Barr virus genome to 64
      kilobase pairs.
AB  - Transformation-competent, replication-defective Epstein-Barr virus (EBV)
      recombinants which are deleted for 18 kbp of DNA encoding the largest EBNA intron
      and for 58 kbp of DNA between the EBNA1 and LMP1 genes were constructed. These
      recombinants were made by transfecting three overlapping cosmid-cloned EBV DNA
      fragments into cells infected with a lytic replication-competent but
      transformation-defective EBV (P3HR-1 strain) and were identified by clonal
      transformation of primary B lymphocytes into lymphoblastoid cell lines. One-third
      of the lymphoblastoid cell lines were infected with recombinants which had both
      deletions and carried the EBNA2 and EBNA3 genes from the transfected EBV DNA and
      therefore are composed mostly or entirely from the transfected EBV DNA fragments.
      The deleted DNA is absent from cells infected with most of these recombinants, as
      demonstrated by Southern blot and sensitive PCR analyses for eight different
      sites within the deleted regions. Cell growth and EBNA, LMP, and BZLF1 gene
      expression in lymphoblastoid cell lines infected with these recombinants are
      similar to those in cells infected with wild-type EBV recombinants. Together with
      previous data, these experiments reduce the complexity of the EBV DNA necessary
      for transformation of primary B lymphocytes to 64 kbp. The approach should be
      useful for molecular genetic analyses of transforming EBV genes or for the
      insertion of heterologous fragments into transforming EBV genomes.

PMID- 7815565
TI  - The roles of eighteen baculovirus late expression factor genes in transcription
      and DNA replication.
AB  - A set of 18 plasmid subclones of the Autographa californica nuclear polyhedrosis
      virus genome supports expression from a late viral promoter in transient
      expression assays (J. W. Todd, A. L. Passarelli, and L. K. Miller, J. Virol.
      69:968-974, 1995). Using this set of plasmids, we have assigned a role for each
      of the 18 genes required for optimal late gene expression with respect to its
      involvement at the levels of transcription, translation, and/or DNA replication.
      RNase protection analyses demonstrated that all of the known late expression
      factor genes (lefs) affected the steady-state level of reporter gene RNA. Thus,
      none of the lefs appeared to be specifically involved in translation. A subset of
      the lefs supported plasmid replication; ie-1, lef-1, lef-2, lef-3, p143, and p35
      were essential for plasmid replication, while ie-n, lef-7, and dnapol had
      stimulatory effects. The predicted sequence of lef-7 suggests that it is a
      homolog of herpesvirus single-stranded DNA-binding protein (UL29). The role of
      p35 in plasmid replication appears to be suppression of apoptosis, because p35
      could be functionally replaced in the replication assay by either Cp-iap or Op
      iap, two heterologous baculovirus genes which suppress apoptosis by a mechanism
      which appears to differ from that of p35. Thus, one or more of the replication
      related lefs or the process of plasmid replication appears to induce cellular
      apoptosis. Our results indicate that the remaining lefs, lefs 4 through 11, p47,
      and 39K (pp31), function either at the level of transcription or at that of mRNA
      stabilization.

PMID- 7815568
TI  - This month in investigative urology. Commentary on immunotherapy, gene therapy
      and cancer.

PMID- 7815567
TI  - Characterization of nuclear protein binding to a site in the long terminal repeat
      of a murine leukemia virus: comparison with the NFAT complex.
AB  - We previously identified a protein-binding site (MLPal) that is located
      downstream of the enhancer element in the long terminal repeat (LTR) of a mink
      cell focusing-forming (MCF) murine leukemia virus (F. K. Yoshimura, K. Diem, H.
      Chen, and J. Tupper, J. Virol. 67:2298-2304, 1993). We determined that the MLPal
      site regulates transcription specifically in T cells and affects the
      lymphomagenicity of the MCF isolate 13 murine leukemia virus with a single
      enhancer repeat in its LTR. In this report, we present evidence that two
      different proteins, a T-cell-specific protein and a ubiquitous protein, bind the
      MLPal site in a sequence-specific manner. By mutational analysis, we determined
      that the T-cell-specific and the ubiquitous proteins require different
      nucleotides in the MLPal sequence for DNA binding. By competitive electrophoretic
      mobility shift assays, we demonstrated that the T-cell-specific protein that
      binds MLPal is identical or similar to a protein from nonactivable T cells that
      interacts with the binding site of the nuclear factor of activated T cells
      (NFAT). Unlike the NFAT-binding site, however, the MLPal site does not bind
      proteins that are inducible by T-cell activation. We observed that the MLPal
      sequence is conserved in the LTRs of other mammalian retroviruses that cause T
      cell diseases. Furthermore, the MLPal sequence is present in the transcriptional
      regulatory regions of cellular genes that either are expressed specifically in T
      cells or are commonly rearranged by provirus integration in thymic lymphomas.
      Thus, the MLPal-binding proteins may play a role in the transcriptional
      regulation not only of the MCF virus LTR but also of cellular genes involved in T
      cell development.

PMID- 7815569
TI  - Genetic factors in calcium oxalate stone disease.

PMID- 7815570
TI  - In situ tunneled bowel flap tubes: 2 new techniques of a continent outlet for
      Mainz pouch cutaneous diversion.
AB  - In Mainz pouch continent cutaneous urinary diversion, introduction of the in situ
      tunneled appendix as the continent outlet in 1990 has simplified the surgical
      technique and greatly increased the acceptance of the procedure. Based on the
      results of long-term animal studies, 2 new techniques of a continent outlet were
      randomly used with a Mainz pouch 1 procedure (ileocecal pouch) in 17 patients in
      whom the appendix was not available or usable for construction of a continent
      outlet. According to the flap valve principle of the tunneled appendix, in 17
      patients a small caliber conduit was created from large bowel wall at the lower
      pole of the cecum and was tunneled in situ under the mucosa. In technique 1
      (seromuscular bowel flap tube), a tube lined by serosa was created from a
      pedicled island flap of large bowel wall in 11 patients. In technique 2 (full
      thickness bowel flap tube), a tube lined by mucosa was created from a pedicled
      flap of large bowel wall in 6 patients. After a mean followup of 8 months (range
      2 to 17) 16 of 17 patients catheterize the reservoir at intervals of 4 to more
      than 6 hours using 14 to 16F catheters and are continent day and night without
      leakage. The only major complication in this series was incontinence in 1 patient
      with a seromuscular bowel flap tube who died of metastatic tumor 6 months
      postoperatively.

PMID- 7815571
TI  - Use of ultrasound and cystoscopically guided pancreatic allograft biopsies and
      transabdominal renal allograft biopsies: safety and efficacy in kidney-pancreas
      transplant recipients.
AB  - The use of allograft biopsies to guide treatment after solid organ
      transplantation is a valuable tool in the detection and treatment of rejection.
      Prior development and use of the cystoscopically guided pancreatic allograft
      biopsy have allowed for more accurate and timely diagnosis of pancreatic
      allograft dysfunction, possibly contributing to our 1-year pancreas graft, renal
      allograft and patient survival rates of 87.1%, 88.5% and 96.8%, respectively. We
      reviewed our experience, examining efficacy and complication rates of pancreas
      and kidney biopsies in 31 cadaveric pancreas or combined kidney and pancreas
      transplants performed between June 1990 and February 1992 with at least 1 year of
      followup. There were 94 pancreas, 54 kidney and 53 duodenal mucosal biopsies in
      29 evaluable patients. This biopsy technique uses a 24.5F side-viewing
      nephroscope to view the cystoduodenostomy, with the duodenum acting as a portal
      for biopsy needles into the pancreas. Pancreatic tissue is obtained with either
      an 18 gauge, 500 mm. Menghini aspiration/core needle or an 18 gauge, 500 mm. Roth
      core needle. Percutaneous renal allograft biopsies are performed independently or
      simultaneously with the pancreas biopsies using a 16 gauge spring loaded needle.
      Pancreas biopsies were prompted by clinical indications of rejection (decreased
      urinary amylase, increased serum amylase or increased serum creatinine) or by
      protocol (10, 21 and 40 days postoperatively). Among the biopsies 30% were
      required by protocol, of which 10 (36%) revealed abnormal pathological findings
      and 5 (18%) showed evidence of occult cellular rejection. Renal biopsies
      demonstrated rejection in 69% of the cases. Of simultaneous pancreas/kidney
      biopsies 33% revealed concomitant rejection. A total of 88 Menghini needles with
      170 passes was used in 73 biopsy attempts, yielding 126 tissue cores with a 16%
      complication rate. A total of 41 Roth needles was used with 73 passes in 34
      biopsy attempts, yielding 55 tissue cores with a complication rate of 21%.
      Complications included self-limited bleeding from the biopsy site in 13% of the
      cases, bleeding requiring clot evacuation and fulguration in 1% and asymptomatic
      hyperamylasemia in 12%. Renal biopsy complications included 1 arteriovenous
      fistula (2%). We conclude that ultrasound and cystoscopically guided pancreatic
      allograft biopsy and percutaneous renal allograft biopsies are safe and essential
      methods of obtaining tissue for histological diagnosis without serious sequelae.
      The Menghini and Roth needles in cystoscopically guided pancreatic allograft
      biopsy have similar yield and complication rates in obtaining pancreatic tissue,
      although they require different performance techniques. In some cases both
      needles are necessary and are complementary in obtaining adequate
      tissue.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7815572
TI  - Transplantation of pediatric cadaver kidneys into adult recipients.
AB  - Between July 1987 and July 1993, 762 renal allografts were transplanted into
      adult recipients at our institution. A total of 83 adults received cadaveric
      renal transplants from donors aged 5 months to 10 years, while 100 adults who
      received adult cadaver kidneys during the same period served as a comparison
      group. Cyclosporine based immunosuppression was used. No difference between the 2
      groups was found with respect to recipient age, recipient sex, primary renal
      disease, HLA matching or the number of recipients with a previous transplant.
      Actual patient (graft) survivals at 1 and 3 years were 91% (77%) and 86% (68%),
      respectively, for recipients of pediatric kidneys compared to 99% (92%) and 90%
      (80%), respectively, for recipients of adult kidneys. Pediatric kidney recipients
      were more likely to encounter renovascular complications (13% versus 4%, p =
      0.023) and more likely to have episodes of acute rejection (p = 0.018). Serum
      creatinine was equal in the 2 groups at 1 year following transplantation (p =
      0.63).

PMID- 7815573
TI  - Growth and function of en bloc infant kidney transplants: a preliminary study.
AB  - We evaluated the growth and function of 21 pairs of en bloc infant kidneys
      transplanted into adult recipients. Serum creatinine, 99mtechnetium
      diethylenetriaminepentaacetic acid glomerular filtration rates, kidney volumes
      and resistive indexes were determined at 1 to 3, 3 to 6 and beyond 6 months, and
      compared using repeated measures analysis of variance tests. En bloc kidneys grew
      at a statistically significant rate (p < 0.001), for example nearly 2-fold in 3
      to 6 months (209 +/- 69 cc from 132 +/- 70 cc), and approaching 3-fold at 6
      months and longer (325 +/- 106 cc). Similarly, the glomerular filtration rates
      increased almost 4-fold (83 +/- 52 ml. from 23 +/- 11 ml. per minute) and 5-fold
      (121 +/- 45 ml., p < 0.001), respectively, during the same periods. Resistive
      indexes remained at normal range (0.60 to 0.63). Recipient blood pressure was
      normal. Our study shows that infant en bloc kidney transplants grow rapidly and
      provide excellent function to the adult recipient.

PMID- 7815574
TI  - Combined use of bowel and the artificial urinary sphincter in reconstruction of
      the lower urinary tract: infectious complications.
AB  - Combined use of the artificial urinary sphincter and bowel in reconstruction of
      the lower urinary tract is currently being performed with increasing frequency.
      We reviewed our experience with 31 patients undergoing augmentation cystoplasty
      and insertion of the artificial urinary sphincter with respect to device
      infections to determine if a single operation was associated with increased
      morbidity compared to staged procedures. Of the patients who underwent
      simultaneous reconstruction 50% had prosthetic infections as opposed to 9.5% when
      the procedure was staged. More than half of the infections presented longer than
      1 year after placement of the artificial urinary sphincter. The lowest incidence
      of device infection occurred in patients who underwent a staged procedure with
      implantation of the artificial urinary sphincter initially followed by
      augmentation cystoplasty. The discrepancy in infection rates between single and
      staged procedures is dramatic in this series and, therefore, a staged approach is
      recommended to decrease infectious complications.

PMID- 7815575
TI  - Simplified urinary drainage following orthotopic or continent bladder
      replacement.
AB  - A simplified urinary drainage system is described for orthotopic or
      catheterizable continent urinary diversion. The patient has a single urethral or
      suprapubic Foley catheter draining the urinary reservoir, decreasing nursing work
      load and possibly allowing for earlier discharge of the patient from the
      hospital.

PMID- 7815576
TI  - Diversion.

PMID- 7815577
TI  - Neuroanatomy of the external urethral sphincter: implications for urinary
      continence preservation during radical prostate surgery.
AB  - Post-prostatectomy urinary incontinence probably is multifactorial and
      sphincteric nerve injury could be a contributing cause. Controversy still exists
      regarding the innervation of the external sphincter, and currently pudendal nerve
      injury is not believed to be an etiological factor in post-prostatectomy urinary
      incontinence. To understand better the sphincter and its innervation, we
      undertook an anatomical and histological study of 18 adult male cadavers, which
      revealed that the external urethral sphincter receives part of its innervation
      through special branches originating from the dorsal nerve of the penis after it
      splits from the pudendal nerve. These nerve branches were located 0.3 to 1.3 cm.
      from the prostatic apex, and in 50% of the cadavers they were identified only
      unilaterally or had only 1 branch on each side. The proximity of these nerves to
      the prostatic apex may make them liable to injury during radical prostatectomy.
      These nerves are most likely sensory in nature although the presence of motor
      components cannot be completely ruled out. Injury to these nerves may explain
      several features of post-prostatectomy urinary incontinence.

PMID- 7815578
TI  - Urodynamic findings in patients with diabetic cystopathy.
AB  - To ascertain the relationship between voiding dysfunction associated with
      diabetes and bladder and sphincter behavior, the video urodynamic studies of 182
      patients were retrospectively analyzed. Patients were classified based on
      urodynamic diagnosis and the presence or absence of signs of sacral cord
      involvement. Urodynamic findings were classified as either detrusor
      hyperreflexia, impaired detrusor contractility, detrusor areflexia, indeterminate
      and normal. The results indicate that mean bladder capacity was 485 +/- 89.3 ml.
      with a mean first sensation of filling of 298 +/- 67.4 ml. Of the 182 patients
      100 (55%) had detrusor hyperreflexia, 42 (23%) had impaired detrusor
      contractility, 20 (11%) had indeterminate findings, 19 (10%) had detrusor
      areflexia and 1 (1%) was normal. Bladder outlet obstruction occurred in 66
      patients (36%), all men (57%). The diagnosis was isolated in 24 patients (36%) or
      in combination with another diagnosis in 42 (74%). However, if one considers the
      presence of sacral cord signs (42 patients), the most common urodynamic diagnoses
      were either impaired detrusor contractility in 21 (50%) or detrusor areflexia in
      10 (24%). These data suggest that classical diabetic cystopathy is not the most
      common urodynamic findings in patients with diabetes mellitus and voiding
      dysfunction, and in fact these patients present with variable pathophysiological
      findings. These findings demonstrate the importance of urodynamic studies in
      diagnosing voiding dysfunction in diabetics before initiation of therapy.

PMID- 7815579
TI  - Clean intermittent catheterization in spinal cord injury patients: long-term
      followup of a hydrophilic low friction technique.
AB  - Clean intermittent self-catheterization is an established option in bladder
      management of spinal cord injury patients. Several early and a small number of
      long-term studies have reported good preventive or therapeutic effects on
      hydronephrosis, vesicourethral reflux, urinary tract infection and incontinence.
      Most reports describe the use of small catheters and liberal use of jelly but
      urethral complications, such as strictures and false passages, seem to increase
      with the length of followup. All 30 spinal cord injury patients in this
      retrospective study had used disposable hydrophilic, low friction catheters from
      the early shock phase to a median of 7 years (range 5 to 9). There were 26 upper
      motor neuron and 4 lower motor neuron lesions. After tap water soaking, the
      surface layer of the catheter coating has a friction constant more than 10 times
      lower than that for a regular plastic catheter (Nelaton) with chlorhexidine
      jelly. There was no hydronephrosis, pyelonephritis or renal scarring. In 3
      patients who had decreased the clean intermittent self-catheterization regimen,
      signs of upper tract dilatation developed but the excretory urogram returned to
      normal after correction of the regimen. Of 30 patients 12 (40%) maintained
      sterile urine, while 4 of the remaining 18 with bacteriuria had episodes of
      urinary sepsis and chronic infections. Two patients had epididymitis. Of 6 men
      with occasional insertion difficulties when the clean intermittent self
      catheterization regimen started after the indwelling catheter had been removed 4
      showed yielding signs of strictures during the subsequent clean intermittent self
      catheterization regimen. In 1 patient 2 dilation attempts had failed but the
      patient can perform the clean intermittent self-catheterization regimen. One
      patient with Crohn's disease had advanced urethral changes in the acute phase but
      could perform clean intermittent self-catheterization with a small catheter. One
      patient has had recurrent modifications of the urethral wall but no development
      of a false passage. The study indicates that patients who use hydrophilic low
      friction low friction catheters do as well as or better than patients using
      conventional catheters. Above all, there is no increase in severe urethral
      complications with time after injury. Progression towards strictures after early
      urethral trauma seems to be preventable by the use of this catheter.

PMID- 7815580
TI  - Patient satisfaction and the LoFric catheter for clean intermittent
      catheterization.
AB  - A pilot study was initiated to determine patient satisfaction with the use of a
      newly available pre-lubricated, hydrophilic, disposable LoFric* catheter for
      clean intermittent catheterization. The study population consisted of 16 new
      patients and 25 experienced with clean intermittent catheterization. Patients
      were asked questions regarding convenience, ease of handling, comfort and general
      opinion of the catheters. Four new and 8 experienced patients dropped out of the
      study. Of the new patients who completed the study 75% found clean intermittent
      catheterization less troublesome than expected and all wish to continue using the
      catheter. Of the experienced patients 81% had a more favorable general opinion of
      the disposable than of the previous catheter, 81% found the disposable catheter
      to be more convenient and 88% thought it was easier to handle. It appears that
      most people will be satisfied with the disposable catheter and will prefer it as
      an alternative to a plastic catheter with lubrication applied by the patient.

PMID- 7815581
TI  - Urinary incontinence.

PMID- 7815582
TI  - The use of duplex ultrasound in the assessment of arterial supply to the penis in
      vasculogenic impotence.
AB  - Impotence may be caused by arterial disease affecting the vessels supplying the
      corpora cavernosa. Color duplex ultrasound was used to measure the peak systolic
      velocity and systolic rise time in the deep penile arteries in 22 impotent men
      following papaverine stimulation. The results were compared with the findings of
      selective internal pudendal pharmaco-arteriography. A further comparison was made
      using color duplex ultrasound with 37 impotent men who all responded well to
      papaverine. A systolic rise time of 110 msec. or more was found to be the best
      discriminant of disease in the arteries supplying the corpora giving a positive
      predictive value of 0.92. A long systolic rise time in a papaverine responder may
      indicate that the arterial supply is borderline or that the arterial flow is
      maximal and that the problem lies on the sinusoidal-venous side. It appears that
      in the absence of a pathological condition there is a large surplus arterial
      supply.

PMID- 7815583
TI  - The correlation of cavernous systolic occlusion pressure with peak velocity flow
      using color duplex Doppler ultrasound.
AB  - This prospective study involved 27 patients who underwent dynamic infusion
      cavernosometry/cavernosography and color duplex Doppler ultrasound. Phase III
      dynamic infusion cavernosometry/cavernosography determination of cavernous artery
      systolic occlusion pressure and color duplex Doppler measurements of peak
      velocity flow were performed. Four subpopulations were defined: 1) normal
      cavernous artery systolic occlusion pressure and peak velocity flow, 2) abnormal
      systolic occlusion pressure and normal peak velocity flow, 3) normal systolic
      occlusion pressure and abnormal peak velocity flow, and 4) abnormal systolic
      occlusion pressure and peak velocity flow. Peak velocity flow significantly
      correlated with cavernous artery systolic occlusion pressure and, using a normal
      value of greater than 25 cm. per second, resulted in a sensitivity and
      specificity of 95%. The positive predictive value of an abnormal peak velocity
      flow was calculated to be 95%. We conclude that peak velocity flow is an
      effective, reliable and noninvasive means of evaluating corporeal arterial
      function in an office setting.

PMID- 7815584
TI  - Papaverine topical gel for treatment of erectile dysfunction.
AB  - Intracavernous injection of vasoactive substances has been shown to be an
      effective means of treatment of organic erectile dysfunction. However, up to 50%
      of men eventually discontinue treatment often because of lack of spontaneity and
      needle phobia. This study was done as a phase I, placebo controlled, nonblinded
      investigation of the safety and efficacy of a topical papaverine gel in the
      treatment of erectile dysfunction. Of 20 men with organic impotence 17 completed
      the trial and 13 of these patients had spinal cord injuries. After application of
      a 15% and 20% papaverine base gel to the scrotum, perineum and penis, cavernous
      artery diameter was significantly increased (36%, p < 0.001) as assessed by color
      flow Doppler ultrasound. Peak systolic flow velocity increased 26%. Only 3 of 14
      patients achieved an increase in cavernous artery diameter of 75% or more and 2
      of 14 had a peak systolic flow velocity of 25 cm. per second or more after
      application of a topical base gel. Similar findings were present when only the
      patients with spinal cord injury were analyzed. The effect of a papaverine base
      in producing flow alterations to the penis is dose-dependent. A diminution in
      blood pressure was present at 15 and 30 minutes after application to the forearm,
      and the heart rate diminished from 68 to 62 beats per minute after application to
      the genitalia. No patient was symptomatic. Serum papaverine levels were not
      elevated over pre-application values. No hepatotoxic effects were demonstrated.
      Full clinical erections (mean duration 38.7 minutes) were present in 3 patients
      but were also present with the placebo preparation (mean duration 8.0 minutes).
      In conclusion, topical papaverine gel appears to be safe and well tolerated after
      application to the genitalia, and increases blood flow to the penis with a 15%
      and 20% base preparation. Minimal systemic absorption occurs and, thus, effects
      are probably from local absorption. Topical therapy appears to augment reflex
      erections in the spinal cord injury patient and may be especially beneficial in
      this population. Further investigation is warranted at higher concentrations or
      in combination with different skin absorption enhancers.

PMID- 7815585
TI  - Management of nondilatable cavernous fibrosis with the use of a downsized
      inflatable penile prosthesis.
AB  - The basic underlying cause of inability to implant a penile prosthesis is
      cavernous fibrosis resulting in unsatisfactory cavernous dilation. During the
      last 3 years, 20 patients with severe cavernous fibrosis underwent penile
      prosthetic implantation with a downsized inflatable penile prosthesis, obviating
      the need for additional cavernous reconstruction. After a mean followup of 20
      months 19 of the 20 patients had a functional device with only 1 requiring
      explantation for infection. We believe that this downsized penile prosthesis is a
      valuable addition to the urological armamentarium when considering reimplantation
      or implantation in a patient with intracavernous fibrosis and scarring.

PMID- 7815586
TI  - Corrective procedures for penile shortening due to Peyronie's disease.
AB  - Peyronie's disease is a poorly understood scarring condition of the tunica
      albuginea that often causes pain and deformity of the penis. When Peyronie's
      disease is present predominantly unilaterally, bending of the penis to 1 side
      occurs. With bilateral or circumferential disease the tunica albuginea does not
      expand, and penile shortening and/or narrowing occurs. We performed unilateral or
      bilateral penile lengthening procedures on 22 patients with penile shortening due
      to Peyronie's disease who refused a procedure, such as tucks or the Nesbit
      operation, that might result in further penile shortening. Five men underwent
      incision of the plaque and dermal patch without implantation of a penile
      prosthesis, while 8 underwent penile implantation plus incisions in the tunica
      albuginea without patches, and 5 underwent circumferential incision of the tunica
      albuginea and its septum with patching and placement of a penile implant.
      (Average length gain with circumferential incision was 1.5 inches with this
      procedure.) There were 18 patients available for followup: 1 had penile skin
      slough secondary to a compression dressing, 2 required removal of the implant and
      replacement at a later date, and 2 had progressive penile shortening after dermal
      patch requiring subsequent prosthesis implantation. Penile lengthening procedures
      to correct functionally significant penile shortening can be performed
      successfully, although significant complications were experienced.

PMID- 7815587
TI  - Extensive corporeal fibrosis after penile irradiation.
AB  - A potent man with early signs and symptoms of Peyronie's disease 3 months in
      duration received 1,200 rad of external beam radiation to the penis and presented
      5 months later with impotence. Physical examination revealed diffusely woody
      indurated corporeal tissue. Nocturnal penile tumescence testing was abnormal and
      pharmaco-cavernosometry demonstrated diffuse corporeal veno-occlusive
      dysfunction. Treatment by penile injections was unsuccessful. During penile
      prosthesis implantation bilateral rubbery erectile tissue was encountered,
      requiring extensive bilateral corporotomy and sharp corporeal tissue excision for
      prosthesis insertion. Histological analysis of excised corporeal tissue
      demonstrated extensive corporeal fibrosis and arterial vasculopathy. Computer
      assisted color histomorphometry revealed that the mean percentage of trabecular
      smooth muscle area to total erectile tissue area was 26.5 +/- 15.8 (normal 40 to
      52%). Immunohistochemical staining with desmin confirmed extensive fibrosis. The
      most likely explanation for severe corporeal fibrosis is penile irradiation. The
      hypothesized mechanism of radiation associated fibrosis is ionizing injury to the
      endothelial cells of the lacunar spaces and cavernous/helicine arteries, which
      induced irreversible corporeal extracellular matrix structural changes. Penile
      irradiation, like vascular disease and priapism, is a potential cause of diffuse
      corporeal fibrosis.

PMID- 7815588
TI  - A new system for descriptive classification of stones in the upper urinary tract.
AB  - A descriptive classification is proposed to stratify upper urinary tract stones
      by their number, size and location. The system considers the minimal but most
      important factors regarding the choice of surgical treatment and its success. Its
      principle is adaptable to more complex staging systems already existing.
      Practical use of the system has shown it to reflect clinical events, and its
      simplicity offers an opportunity for compliance in routine clinical study. It
      facilitates easy computerized stratification of stones in the upper urinary
      tract.

PMID- 7815589
TI  - Renal and diaphragmatic endometriosis de novo associated with hormone replacement
      therapy.
AB  - Endometriosis involving the kidneys is rare. To our knowledge we report the first
      case in which kidney involvement was the initial manifestation of this condition.
      Because of previous bilateral oophorectomy the diagnosis of endometriosis was
      improbable. Hormone replacement therapy was implicated in the etiology.

PMID- 7815590
TI  - Hernia after dorsal incision into lumbar region: a case report and review of
      pathogenesis and treatment.
AB  - Because of few associated complications and rapid recovery, dorsal incision into
      lumbar region has experienced a resurgence in popularity for the treatment of a
      variety of renal and upper ureteral disorders. We report a case of pyelolithotomy
      via the dorsal approach in which a symptomatic lumbar incisional hernia
      subsequently developed, which to our knowledge is a previously unreported
      complication of this approach. Reconstruction of this lumbar hernia defect
      necessitated the application of synthetic mesh graft sandwiched by mobilized
      muscle flaps. The entire repair was then sutured inferiorly to the iliac crest
      using drill holes. Outcome was durable and successful. The pathogenesis and
      treatment of this complication are discussed.

PMID- 7815591
TI  - Ethanolamine sclerotherapy of a renal cyst.
AB  - We report the effective use of 5% ethanolamine oleate to sclerose a large simple
      renal cyst. The comparative advantages of ethanolamine versus other sclerosants
      are discussed in terms of adverse effects, availability and convenience.
      Guidelines to optimize sclerotherapy with ethanolamine are provided.

PMID- 7815592
TI  - Pseudolymphoma of the kidney: a case report.
AB  - We report a case of pseudolymphoma of the kidney. Examination of a surgically
      resected specimen showed that the lesion was localized in the renal parenchyma.
      It was impossible to achieve an accurate preoperative diagnosis clinically or
      radiologically because there were no characteristic findings. To the best of our
      knowledge no previous case of a pseudolymphoma localized in the renal parenchyma
      has been reported.

PMID- 7815593
TI  - Autotransplantation for intractable loin pain: report of a case with long-term
      followup.
AB  - We report a case of autotransplantation performed 21 years ago in a patient
      suffering from intractable loin pain. Long-term followup, the pathogenesis of
      pain in regard to renal innervation and the value of autotransplantation as a
      form of complete sensory denervation are discussed.

PMID- 7815594
TI  - Lymphoproliferative disease presenting as obstructive uropathy after renal
      transplantation.
AB  - Lymphoproliferative disorders occur with a greater frequency in recipients of
      solid organ transplants. Unlike in the general population, these tumors tend to
      arise in extranodal sites and are often confined to a single organ. We report on
      a patient with lymphoproliferative disease confined to the hilum of the renal
      allograft. The only clinical clue to the presence of the tumor was an increase in
      the serum creatinine secondary to ureteral obstruction by the mass.

PMID- 7815596
TI  - Pseudo-crossed renal ectopia secondary to ureteropelvic junction obstruction.
AB  - To our knowledge we report the first case of pseudo-crossed renal ectopia without
      an apparent displacing retroperitoneal mass that was documented on sequential
      radiological studies. Ureteropelvic junction obstruction of the crossed kidney
      appeared to be the cause of pseudo-crossed renal ectopia. Our case is compared
      with previously described instances of pseudo-crossed renal ectopia and the
      pathophysiological basis of this condition is discussed.

PMID- 7815595
TI  - Acquired renal cystic disease and renal cell carcinoma in an allograft kidney.
AB  - Acquired renal cystic disease has been reported in the kidneys of patients with
      end stage renal disease who have been untreated, treated with dialysis or
      undergone renal transplantation. The incidence of renal tumor development in
      patients with acquired renal cystic disease is greater than 5% in those
      undergoing chronic hemodialysis. Recently, cases of renal cell carcinoma
      occurring with acquired renal cystic disease of the native kidneys of transplant
      recipients have been reported. Transplant patients have an increased incidence of
      malignancy when compared to the general population. Including our case, 19 cases
      of de novo renal neoplasms developing in renal allografts have been reported. To
      the best of our knowledge we report the longest interval to presentation of a de
      novo renal tumor in an allograft kidney (228 months) and the first case of renal
      cell carcinoma associated with acquired renal cystic disease in an allograft
      kidney.

PMID- 7815597
TI  - Ureteral amyloid deposits of beta 2-microglobulin origin in both kidney
      recipients of 1 donor.
AB  - We report on 2 renal transplant recipients with ureteral amyloid deposits, each
      of whom received 1 kidney from the same donor. Ureteral stenosis developed in
      both cases. Immunohistochemistry revealed beta 2-microglobulin derived AB amyloid
      within the stenotic parts of the ureters, which to our knowledge has not been
      described previously at that site. Usually AB amyloid is found in patients on
      long-term hemodialysis. Amyloid transfer by transplantation as a possible cause
      for ureteral stenosis was excluded because the donor had had normal renal
      function and autopsy showed no evidence of amyloidosis. It is more likely that
      the secondary deposit of AB amyloid in the transplanted ureters was facilitated
      by preexisting ischemic ureteral damage.

PMID- 7815599
TI  - Transureterocalicostomy: an alternative internal diversion technique.
AB  - We report a case of an infiltrating retroperitoneal tumor that completely
      enveloped and obstructed the mid third of the left ureter. After resection of the
      tumor, including a 10 cm. long segment of ureter, the upper left ureter was
      successfully diverted to the upper calix of the right ectopic kidney
      (transureterocalicostomy). To our knowledge our report represents the first case
      of such surgery.

PMID- 7815598
TI  - Ureteral obstruction caused by a thromboembolic infarct.
AB  - A case of a healed fibrotic ureteral infarct secondary to vascular occlusion+ by
      thromboemboli that caused a ureteral filling defect and obstruction is reported.

PMID- 7815600
TI  - Behcet's syndrome and vesicovaginal fistula: an unusual complication.
AB  - We present an unusual case of a spontaneous vesicovaginal fistula occurring with
      Behcet's syndrome. Recommendations and precautions for the management of this
      situation are briefly discussed.

PMID- 7815601
TI  - Gangrene of the bladder due to over distention.
AB  - Massive over distention of the bladder in a man caused necrosis of the mucosa and
      submucosa, which then separated from the muscularis of the bladder. Suprapubic
      removal of the necrotic tissue followed by prolonged drainage resulted in
      regeneration of the mucosa. Normal bladder function returned after transurethral
      resection of the obstructing prostate. Diagnosis of this rare condition is
      confirmed when necrotic tissue occludes the eyes of catheters so that fluid can
      be instilled into but not removed from the bladder.

PMID- 7815602
TI  - Surgical treatment of verrucous carcinoma of the bladder unassociated with
      bilharzial cystitis: case report and literature review.
AB  - Verrucous carcinoma of the bladder unassociated with bilharzial cystitis is rare
      with only 6 cases reported to date. Verrucous carcinoma of the bladder, like that
      involving the cervix, vagina, oral cavity, perineum and lower extremities, may
      invade surrounding structures but remain surgically curable. Although it is
      similar to condyloma acuminatum, verrucous carcinoma is considered malignant
      because of its invasive growth pattern and it should be treated accordingly.
      However, no evidence of metastases has been noted to date. To our knowledge we
      report the first case of extravesical extension of verrucous carcinoma of the
      bladder that was treated successfully by surgical removal.

PMID- 7815603
TI  - Radical cystectomy and lower urinary tract reconstruction after cardiac allograft
      transplantation.
AB  - The risk of a malignancy developing as a consequence of long-term
      immunosuppression after allograft transplantation is well documented. To our
      knowledge we report on the first cardiac allograft recipient to undergo radical
      cystectomy with lower urinary tract reconstruction using a continent Kock ileal
      reservoir with bilateral ureteroileal urethrostomy for squamous cell carcinoma
      that developed 4 years after transplantation.

PMID- 7815604
TI  - Successful treatment of metastatic small cell carcinoma of the bladder with
      methotrexate, vinblastine, doxorubicin and cisplatin therapy.
AB  - A man with metastatic small cell carcinoma of the bladder who was treated with
      methotrexate, vinblastine, doxorubicin and cisplatin therapy achieved complete
      remission with disease-free survival of more than 9 years. The nature of this
      unusual form of bladder carcinoma and the course of the disease in our case are
      discussed.

PMID- 7815605
TI  - Obstructive leiomyoma of the female urethra: report of a case.
AB  - We report a case of leiomyoma of the female urethra and review the literature. A
      mass protruding from the urethral meatus during voiding caused dysuria.
      Urodynamic study showed an obstructive pattern with low maximum urine flow and
      high detrusor pressure in initiating voiding. Cystourethroscopy revealed a mass
      extending from the proximal segment of the left lateral urethral wall into the
      bladder. At transurethral resection of the tumor 12.2 gm. of tissue were excised.
      Histopathological studies confirmed urethral leiomyoma. Surgery completely
      resolved the original symptoms of dysuria.

PMID- 7815606
TI  - Combination chemotherapy and radiotherapy for a locally advanced squamous cell
      carcinoma of the urethra: a case report.
AB  - A 68-year-old patient with advanced stage IVB squamous cell carcinoma of the
      urethra was treated successfully by combined radiation therapy to 5,580 cGy., and
      chemotherapy with 5-fluorouracil and mitomycin. Dramatic response in the size of
      the tumor was noted and on the last day of treatment there was no definite
      evidence of persistent disease. No surgery was performed except for urinary
      diversion. The patient remained without disease for 5.5 years clinically and
      pathologically. In this case the combination of radiation therapy and
      chemotherapy obviated the need for radical surgery. This clinical behavior is
      markedly similar to the behavior of anal canal carcinoma when using a similar
      regimen. Therefore, further clinical investigation for combined modality
      treatment is warranted.

PMID- 7815607
TI  - Balanitis circumscripta plasmacellularis.
AB  - Balanitis circumscripta plasmacellularis typically affects the glans penis and/or
      prepuce, and presents as chronic shiny smooth red-orange plaques. We report on an
      uncircumcised man with 2 moist red-orange lesions of balanitis circumscripta
      plasmacellularis on the glans and penile shaft, which were refractory to topical
      therapy and systemic antibiotics, and review the literature. Clinical morphology,
      microscopic features, differential diagnosis, postulated etiologies and
      treatments are discussed. When balanitis circumscripta plasmacellularis is
      suspected clinically, diagnosis can be readily confirmed by microscopic
      examination of the lesion. Differentiating this lesion from similar lesions is
      essential since it is benign and can be treated relatively easily by
      circumcision.

PMID- 7815608
TI  - The koro (genital retraction) syndrome and its association with infertility: a
      case report.
AB  - The koro syndrome is a psychiatric disorder characterized by acute anxiety and a
      deep-seated fear of shrinkage of the penis and its ultimate retraction into the
      abdomen, which will cause death. Concurrence of the koro (genital retraction)
      syndrome with a pathological condition of the urogenital system has rarely been
      described. We report a case of koro associated with infertility. Within 3 weeks
      of treatment with haloperidol the classic symptoms of koro disappeared. To our
      knowledge this case represents the sixth report of the koro syndrome associated
      with urogenital pathology and the first report of its association with
      infertility.

PMID- 7815609
TI  - Premature emission after spinal cord injury.
AB  - Physicians and psychologists almost always treat premature emission or
      ejaculation as a psychological problem. We report on 6 men who had sudden onset
      of severe premature emission after spinal cord injury. All men suffered spinal
      cord injury related to trauma at the T12-L1 level, and had areflexic bladders
      after the injury. Two men had normal penile sensation. None of the men had
      premature ejaculation before injury with average time of intercourse of 10 to 20
      minutes before organsm. After the injury they noticed emission before or at
      vaginal entry. Two patients reported emission with any sexual thoughts and 1 had
      emission when started in a nonsexual manner. Sexual therapy using squeeze and
      stop/start techniques was unsuccessful in all cases. Patients were started on
      phenoxybenzamine, terazosin or prazosin and reported slight improvement. We
      believe that injury in the conus area of the spinal cord may disinhibit the
      ejaculatory mechanism and allow for premature emission.

PMID- 7815610
TI  - Lymph node metastasis from carcinoma in situ of the penis: a case report.
AB  - Lymph node metastasis from carcinoma in situ of the penis is rare. We report a
      case of carcinoma in situ of the penis that was initially managed with
      circumcision and topical 5-fluorouracil. Subsequently inguinal and para-aortic
      lymph node metastasis developed, which was treated successfully with systemic
      chemotherapy and right inguinal lymph node dissection. The patient is free of
      disease 7 years after initial diagnosis and 3 years after the diagnosis of nodal
      metastasis.

PMID- 7815611
TI  - The value of transrectal ultrasonography in the diagnosis and treatment of
      partial obstruction of the seminal duct system.
AB  - We report a case of male subfertility with ejaculate volume less than 1 cc and
      moderate oligoasthenozoospermia. Partial obstruction of the seminal duct system
      was suspected and transrectal ultrasonography revealed a mullerian duct cyst. We
      confirmed the diagnosis with transperineal puncture and contrast filling of the
      cyst and seminal vesicles. This procedure allowed us to avoid scrotal vasostomy
      and perform conventional vasography as well as to measure the distance between
      the ceiling of the cyst and the urethra, which facilitated subsequent
      transurethral surgery.

PMID- 7815612
TI  - Video laparoscopic excision of a seminal vesicle cyst associated with ipsilateral
      renal agenesis.
AB  - A 6 cm. cystic right seminal vesicle was successfully removed using operative
      laparoscopy. Advantages of the laparoscopic approach over open surgery include
      excellent exposure of the deep pelvic structures and rapid convalescence. Among
      the disadvantages are the potential complications associated with laparoscopic
      transperitoneal access.

PMID- 7815613
TI  - Re: Outcome after temporary vascular occlusion for the management of renal
      trauma.

PMID- 7815614
TI  - Prenatally diagnosed bilateral hyperechoic kidneys with normal amniotic fluid:
      postnatal outcome.
AB  - We evaluated a subset of infants with bilateral markedly hyperechoic "bright"
      kidneys noted prenatally in association with normal amniotic fluid volume during
      gestation. Prenatal ultrasound showed increased renal parenchymal echogenicity
      bilaterally with preservation of the medullary pyramid architecture. These
      children were followed for up to 3 years to determine potential changes in the
      sonographic appearance of the echogenic renal parenchyma and to assess renal
      function. In 3 years 8 cases of bilateral hyperechoic fetal kidneys were
      identified. During postnatal followup renal echogenicity resolved in 4 cases,
      diminished in 1 and remained the same in 3. The serum creatinine and electrolytes
      were normal in all cases followed for more than 3 months. Other renal findings
      included vesicoureteral reflux in 2 of 7 cases, mild pelvic ectasia in 1 and tiny
      medullary calcifications in 1. The specific etiology of increased echogenicity is
      unknown, although 1 infant appeared to have a form of autosomal recessive disease
      with liver hyperechogenicity as well. We conclude that fetuses with bilateral
      hyperechoic kidneys associated with normal amniotic fluid volume have a favorable
      outcome. Ultrasonographic finding of marked parenchymal hyperechogenicity appears
      to improve with time; in our experience renal function is normal and the infants
      thrive. Continued followup is necessary to determine the long-term natural
      history of this phenomenon, as is subsequent prenatal and postnatal evaluation of
      future siblings to assess genetic risk.

PMID- 7815615
TI  - Radiographically documented fecal impaction causing peritoneal dialysis catheter
      malfunction.
AB  - Peritoneal dialysis catheter malfunction is most commonly caused by infection or
      omental occlusion. To our knowledge we report the first case of radiologically
      confirmed fecal impaction resulting in peritoneal dialysis catheter malfunction,
      which resolved with medical management. In patients undergoing peritoneal
      dialysis fecal impaction should be considered in the differential diagnosis of
      catheter malfunction before surgical intervention.

PMID- 7815616
TI  - Unilateral lymphangiectasis of the kidney: an unusual cause of renal enlargement
      in an infant.
AB  - We report on an infant with unilateral renal lymphangiectasia and the absence of
      small cysts in the renal parenchyma or renal hilum. We suggest that renal
      lymphangiectasia be part of the differential diagnosis in children who present
      with unilateral renal enlargement, especially when contrast enhanced computerized
      tomography shows preservation of a rim of renal cortex with decreased attenuation
      of the medulla and/or when ultrasound demonstrates increased echogenicity without
      displacement of the caliceal system.

PMID- 7815617
TI  - Surgical treatment of renovascular hypertension in moyamoya disease: case report
      and review of the literature.
AB  - Moyamoya disease is a rare disorder characterized by progressive occlusive
      cerebral arteriopathy associated with an extensive network of collateral vessels.
      Renovascular hypertension has rarely been associated with this disease. We report
      on a girl with renovascular hypertension and 2 renal artery aneurysms who was
      found to have moyamoya disease. Successful surgical treatment was achieved with
      extracorporeal arterial repair and renal autotransplantation. The relationship
      between moyamoya disease and renovascular hypertension is reviewed.

PMID- 7815618
TI  - Pediatric low energy lithotripsy with the Lithostar.
AB  - Between November 1988 and July 1993, 238 renal stones and 208 ureteral stones
      were treated in 446 pediatric patients using 26 mobile and 2 fixed base Siemens
      Lithostar lithotriptors. The stones were treated by a group of 245 urologists
      using the modified Puigvert technique and the standard shock tube. The success
      rate for renal stones (asymptomatic fragments less than 4 mm.) was 76.6%, stone
      free rate was 67.9%, retreatment rate was 14.1% and ancillary procedures were
      performed in 36.3%. The stone-free rate for ureteral stones was 91.1%,
      retreatment rate was 3.5% and ancillary procedures were performed in 17.7%.
      Anesthesia was required in 31% of the renal and 21% of the ureteral procedures.
      Sepsis in a 6-year-old child after treatment of a ureteral stone was the only
      major complication. Low energy lithotripsy with the Lithostar in our series of
      pediatric patients was safe and effective.

PMID- 7815619
TI  - Perinephric urinoma secondary to neurogenic bladder in myelodysplasia.
AB  - We report on a girl with infected perinephric urinoma and myelodysplasia who
      presented with a febrile urinary tract infection. A complex perinephric fluid
      collection with internal echoes was found on renal ultrasound, necessitating
      placement of a percutaneous drainage tube. Initial urodynamic testing after
      treatment of the infection revealed a noncompliant bladder with an elevated
      detrusor leak point pressure. Neurovesical dysfunction with elevated leak point
      pressure is believed to be the cause of urinoma. Clinical presentation, treatment
      and pathophysiology of this entity are discussed.

PMID- 7815620
TI  - Oxybutynin administration diminishes the high gastric muscular tone associated
      with bladder reconstruction.
AB  - Oxybutynin has a proved role in correcting uninhibited detrusor contractions in
      the intact and the bowel augmented bladder. Beneficial responses to oxybutynin
      have also been noted after gastrocystoplasty. It has been questioned whether this
      response reflects a selective effect on the bladder segment or whether there is
      an additional effect on the gastric patch musculature. We report a case of
      improved function of a previously poorly complaint gastric neobladder caused by
      oxybutynin, thereby demonstrating a direct action on gastric smooth muscle.

PMID- 7815621
TI  - The changing urodynamic pattern in valve bladders during infancy.
AB  - Bladder dysfunction in boys with posterior urethral valves is well documented in
      studies of long-term followup. These reports suggest that dysfunctional bladders
      can be divided into 3 main types, including unstable, low compliant and over
      distended. To our knowledge urodynamic findings at presentation during infancy
      have not been described previously. We report on 16 male patients born between
      1989 and 1993 who presented with symptoms of posterior urethral valves between
      birth and age 5 months, and who were followed with repeated urodynamic
      evaluations for a mean of 19 months. At presentation the bladder was
      hypercontractile with low capacity. During the first 3 years of life, the
      urodynamic pattern changed with vanishing hypercontractility and increasing
      bladder capacity, although instability remained unchanged with emptying
      difficulties. Thus, the 3 patterns of bladder dysfunction reported in older boys
      after resection of posterior urethral valves could not be found in infants and
      small children.

PMID- 7815622
TI  - Congenital hemangiopericytoma of the clitoris.
AB  - Hemangiopericytoma is a rare vascular tumor that is believed to arise from the
      pericyte of Zimmermann. Approximately 10% of cases occur in children and a third
      are congenital. To our knowledge we report the first case of a congenital
      hemangiopericytoma arising from the clitoris, describe its management and review
      the literature.

PMID- 7815623
TI  - Male duplex urinary incontinence.
AB  - Ectopic duplex ureter is a well recognized cause of urinary incontinence in
      female subjects but to our knowledge it has not been documented in a male
      subject. We report on a boy who presented with urinary incontinence secondary to
      an ectopic duplex ureter.

PMID- 7815624
TI  - Tunica vaginalis blanket wrap to prevent urethrocutaneous fistula: an 8-year
      experience.
AB  - An 8-year review of hypospadias repair in patients with a meatus proximal to the
      coronal margin is reported. Fistula rates were compared among 4 groups: 1) loupe
      magnification, 2) tunica vaginalis blanket wrap tissue interposition with loupe
      magnification, 3) operating microscope magnification and 4) tunica vaginalis
      blanket wrap tissue interposition in conjunction with operating microscope
      magnification. Rate of fistula formation with loupe magnification alone was 20%,
      microscope magnification alone was 12% and tunica vaginalis blanket wrap
      interposition with loupes was 9%. When tunica vaginalis blanket wrap tissue
      interposition was used in conjunction with intraoperative microscopy no fistulas
      resulted.

PMID- 7815625
TI  - Circumcision in children with penile block alone.
AB  - Surgical procedures in children are usually performed with the patient under
      general anesthesia. For circumcision and additional dorsal penile nerve block is
      used for postoperative analgesia. We retrospectively evaluated dorsal penile
      nerve block as the only analgesic technique for the relief of intraoperative pain
      in children undergoing circumcision. For 6 months dorsal penile nerve block was
      performed in 454 children 3 to 11 years old (mean 8.15 +/- 2.08 years) as the
      sole preoperative anesthesia. All boys were considered to have had good
      preoperative analgesia. No major complications were reported. Block related
      hematoma was noted in 12 patients (2.6%) and mild local edema occurred in 83
      (18.3%). There was no excessive bleeding and hemostasis was easily achieved. The
      overall average operating time was 7.2 +/- 2.6 minutes (range 6 to 25). General
      anesthesia was added in 13 patients, representing a dorsal penile nerve block
      failure rate of 2.9%. Four boys suffered from erratic pain, while no objective
      cause of failure was recorded in the remaining 9. Average patient age was 5.8 +/-
      2.2 years (range 3 to 10) in the 13 boys and 8.2 +/- 2 years (range 3 to 11) in
      the remaining 441 patients (p < 0.001). Failure was more frequent in children 3
      to 5 years old (15.5%) than in those older than 6 years (1.5%, p < 0.05). Average
      operating time was 20.7 +/- 2.8 minutes (range 15 to 25) in the 13 children and
      6.8 +/- 1.1 minutes (range 6 to 15) in the remaining 441 (p < 0.001). During the
      recovery period, only children from the general anesthesia group suffered from
      nausea and vomiting (9), and pain, agitation and fear (6 boys 3 to 6 years old).
      Average recovery room time was 38.7 +/- 7.4 minutes (range 30 to 60) in children
      with dorsal penile nerve block alone and 95 +/- 9.8 minutes (range 85 to 120) in
      those with additional general anesthesia (p < 0.001). We conclude that dorsal
      penile nerve block alone provides good intraoperative analgesia for circumcision
      in children, particularly those older than 6 years.

PMID- 7815626
TI  - The laparoscopic diagnosis of transverse testicular ectopia.
AB  - Transverse testicular ectopia is a rare but well documented abnormality in which
      both testes descend through 1 inguinal canal. We report on a 14-month-old boy in
      whom laparoscopy was diagnostic for this abnormality. Laparoscopic examination of
      the pelvis is imperative to rule out the presence of mullerian remnants that
      commonly occur in patients with transverse testicular ectopia. Our case further
      supports the use of laparoscopy in patients with nonpalpable undescended testes.

PMID- 7815627
TI  - Laparoscopic orchiopexy for the intra-abdominal testis.
AB  - Laparoscopic orchiopexy was performed in 3 patients with an intra-abdominal
      testis. The laparoscopic approach provides better exposure of the spermatic
      vessels and vas deferens, and is less traumatic compared to the open procedure.
      In 2 patients the spermatic vessels were dissected after incising the posterior
      peritoneum but in 1 a strip of peritoneum overlying the vessels was left to avoid
      inadvertent damage to the spermatic vessels. The testicles could be brought down
      easily to the scrotum and there was no postoperative atrophy in any of the cases.
      Preliminary results suggest that the laparoscopic approach is a suitable,
      minimally invasive alternative to open exploration in patients with salvageable
      abdominal testes.

PMID- 7815628
TI  - Testicular growth after successful varicocele correction in adolescents:
      comparison of artery sparing techniques with the Palomo procedure.
AB  - Testicular growth after varicocele surgery was evaluated in 116 boys 9 to 20
      years old. A total of 88 boys was available for followup testicular examination 3
      to 60 months after successful varicocele repair (mean 25). Left testicular volume
      loss of 2 cc or greater was present preoperatively in 72 of the 88 patients. The
      Palomo procedure was performed in 36 cases and repair using artery sparing
      techniques was done in 36. Mean relative left testicular volume increased 18% in
      the artery sparing group and 21% in the Palomo group. The increase in relative
      testicular volume compared to preoperative volumes was statistically significant
      in both groups (p < 0.05). There was no significant difference in testicular
      growth between the groups and no postoperative testicular atrophy was observed. A
      comparison group of 8 boys with uncorrected varicoceles demonstrated a mean
      relative volume increase of 3% (mean followup 22 months). The increase in testis
      volume in successfully corrected cases was statistically different (p < 0.05)
      from that of uncorrected cases. We conclude that reversal of varix induced
      testicular growth failure occurs only after successful surgical correction. The
      Palomo procedure resulted in equivalent testicular growth compared to the artery
      sparing techniques with fewer complications and no testicular atrophy despite
      intentional ligation of the testicular artery. Based on our data, we believe that
      the Palomo procedure should be the procedure of choice for adolescent varicocele
      correction.

PMID- 7815629
TI  - Adolescent varicocele.

PMID- 7815630
TI  - Measurement of pudendal evoked potentials during feminizing genitoplasty:
      technique and applications.
AB  - We report on 6 patients (average age 13 months) with ambiguous genitalia who
      underwent stimulation of the dorsal neurovascular bundle of the phallus during
      feminizing genitoplasty. Three patients had the adrenogenital syndrome, 1
      underwent removal of a masculinizing adrenal tumor before genital reconstruction,
      1 had mixed gonadal dysgenesis and 1 had male pseudohermaphroditism. Stimulation
      of the dorsal neurovascular bundle with measurement of electromyographic nerve
      conduction latencies was performed before and after ligation of the corporeal
      bodies and excision of the erectile tissue. In all 6 cases electromyographic
      responses were preserved after phallic reduction. Our study clearly shows that
      modern techniques of genital reconstruction allow for preservation of nerve
      conduction in the dorsal neurovascular bundle and may permit normal sexual
      function in adulthood.

PMID- 7815631
TI  - Intralesional treatment of established murine primary renal tumor with
      interleukin-4: localized effect on primary tumor with no impact on metastases.
AB  - In an effort to develop new strategies for immunotherapy of metastatic renal cell
      carcinoma, we investigated the therapeutic potential of interleukin-4 in a
      visceral renal tumor using the murine Renca renal adenocarcinoma model. Renca
      cells were implanted underneath the renal capsule of Balb/c mice to induce a
      primary tumor that spontaneously metastasized to several organs. Established
      primary renal tumors 4 to 6 mm. in diameter were treated by intralesional
      administration of recombinant murine interleukin-4 (IL-4). This treatment caused
      a marked inhibition of the primary tumor growth but had little effect on the
      progression of metastases in the liver, mesentery and lungs. Immunohistochemistry
      studies performed on renal tumor sections showed a macrophage infiltration that
      became predominant 7 days after IL-4 treatment. CD8+ T cells were also observed
      at the periphery and within the tumor. These data suggest that IL-4 mediated a
      potent antitumor effect when administered intralesionally although its effects
      remained localized with no impact on metastases at distant sites. Interleukin-4
      antitumor activity seems to be mediated by recruitment of macrophages and T cells
      in the tumor.

PMID- 7815632
TI  - Biocompatibility of various indwelling double-J stents.
AB  - The biocompatibility of 8 double-J stent brands was evaluated both in vivo, by
      scanning electron microscopy and histological analysis of pig ureters intubated
      for 6 weeks, and in vitro, by cell culture methods. In vivo findings showed that
      superficial epithelial destruction was milder in the ureters intubated with
      hydrogel-coated stents than in those intubated with other stents. Inflammatory
      reactive changes were milder in the ureters intubated with silicone stents than
      in those intubated with other stents, while encrustation was more severe on
      silicone and Grey stents than the others. In vitro, the 3 stent brands made of
      "modified polyurethane" were found to be cytotoxic while the others were not.
      Overall, silicone and hydrogel-coated stents seemed to be more biocompatible than
      the others, and hydrogel-coated stents to be more suitable than silicone stents
      for long-term ureteral stenting, being less prone to encrustation. Although they
      are of an experimental nature, these findings may be of relevance to clinical
      practice.

PMID- 7815633
TI  - Laparoscopic repair of vesicoureteral reflux utilizing the Lich-Gregoir technique
      in the pig model.
AB  - To date, laparoscopic urological surgery has largely been limited to diagnostic
      or ablative procedures. Herein we report our experience with laparoscopic
      reconstructive surgery to perform an extravesical ureteral reimplantation. Seven
      anesthetized pigs with iatrogenic ureteral reflux underwent a laparoscopic
      extravesical ureteral reimplantation. The newly created ureteral tunnel varied
      from 2 to 4 cm. In 3 pigs, the tunnel was created with tacking staples, while in
      the other 4 pigs, the tunnel was created with intracorporeal suturing techniques
      using a 3-zero polyglyconate running suture. The procedure required an average of
      132 minutes. There was one anesthetic death. There were no urinary tract
      infections. At 3 to 8 weeks after reimplantation, the cystograms were repeated on
      5 pigs. One of 2 stapled reimplant pigs still had reflux; 1 of 3 sewn reimplant
      pigs had reflux. At 6 months following the reimplantation, only 1 pig had
      residual grade I reflux and this was a sutured reimplantation. None of the
      stapled reimplantations exhibited any residual reflux on the surgical side;
      however, in 1 animal a submucosal staple was noted at the time of harvest.

PMID- 7815634
TI  - Human chorionic gonadotropin (hCG) fails to stimulate gonocyte differentiation in
      newborn mouse testes in organ culture.
AB  - The primitive germ cells within the postnatal testis differentiate through
      several steps to form primary spermatocytes, which are required for postpubertal
      spermatogenesis. It is postulated that this germ cell development is controlled
      by the hypothalamic-pituitary-gonadal axis. To study the effect of human
      chorionic gonadotropin (hCG) on postnatal testicular germ cell differentiation,
      especially on gonocytes, newborn mouse testes (n = 75) were cultured for 7 days
      in vitro. The synthetic serum-free medium contained either hCG or exogenous human
      recombinant mullerian inhibiting substance (MIS) plus transferrin, insulin and
      retinoic acid (TIRA). Fetal calf serum 10% (FCS) was used for control medium.
      Thirty-eight newborn mouse testes were cultured with hCG (0.1 to 2.0 IU/ml). The
      percentages of differentiated type-A spermatogonia were not significantly
      increased compared with synthetic medium alone (NS, p > 0.05), but were only 5 to
      7% (p < 0.001) of that of serum-containing medium. By contrast, normal
      transformation from gonocytes to type-A spermatogonia occurred in newborn mouse
      testes (n = 10) cultured with serum-free medium containing exogenous MIS. The
      percentage of differentiated type-A spermatogonia was approximately 77% (NS, p >
      0.05) of those seen in serum-containing medium. These findings demonstrate that
      the transformation of gonocytes to type-A spermatogonia is regulated by MIS,
      rather than hCG. As early germ cell transformation is deficient in boys with
      cryptorchidism, the role of hCG in the treatment of infertility associated with
      undescended testes should be reevaluated.

PMID- 7815636
TI  - Proliferation of gubernaculum cells induced by a substance of low molecular mass
      obtained from fetal pig testes.
AB  - To investigate the hormonal control of gubernacular development and testicular
      descent we determined the effect of gonadal extracts and various hormones on the
      proliferation of gubernaculum cell cultures established from 55 male pig fetuses
      obtained at 60 to 90 days' gestation. The percentage of descended testes was 0 at
      60, 8% at 70, 40% at 80 and 87% at 90 days' gestation. Significant proliferation
      (as measured by [3H]thymidine incorporation) of gubernaculum, but not 3T3, cells
      was induced by crude testicular but not ovarian extracts, and was directly
      related to its protein concentration. Significant proliferation of gubernaculum
      cells was induced by low molecular mass (< 30 kD) testicular, but not by high
      molecular mass (> 30 kD), testicular and low or high molecular mass ovarian
      extracts obtained by centrifugation of crude extracts in microspin filter
      membranes with a molecular cut-off mass of 30 kD. Proliferation of gubernaculum
      cells induced by the low molecular mass (<30 kD) testicular extract was
      significantly greater than that stimulated by testosterone or
      dihydrotestosterone. Polyacrylamide gel electrophoresis demonstrated a unique
      protein band at approximately 26 kD in the crude and low molecular mass
      testicular, but not in the ovarian, extracts. It is possible that this represents
      a novel peptide hormone secreted by the fetal testis, responsible for stimulating
      the growth of the gubernaculum, thereby mediating testicular descent.

PMID- 7815635
TI  - Characterization and function of histamine receptors in corpus cavernosum.
AB  - Widespread clinical use of H2 antagonists for peptic ulcer disease has been
      associated with reports of impotence. Histamine is a vasoactive amine which is
      endogenously produced in many organs including the penis. To date, 3 histamine
      receptor subtypes (H1, H2 and H3) have been identified. However, the role and
      function of histamine in the corpus cavernosal physiology are poorly understood.
      This study evaluates the in vitro functional characteristics of the 3 histamine
      receptor subtypes in the isolated corpus cavernosal strips from New Zealand White
      rabbits. The isometric responses to histamine and specific histamine receptor
      subtype agonists were assessed, following cyclooxygenase (indomethacin, 10(-5)
      M.), adrenergic (guanethidine, 5 x 10(-6) M.) and cholinergic (atropine, 5 x 10(
      6) M.) blockade, at resting tension and after submaximal precontraction with
      norepinephrine (NE, 2 x 10(-5) M.). Histamine (10(-8) M. to 10(-3) M.) produced
      concentration-dependent contraction from basal and precontracted states and did
      not relax precontracted tissue. The H1 agonist, 2-(2-thiazolyl)ethylamine (10(-8)
      M. to 10(-3) M.), produced a contractile response from both basal and
      precontracted states, while the corporal tissue did not respond to either
      dimaprit, an H2 agonist (10(-8) M. to 10(-5) M.) or R(-)-alpha-methyl-histamine,
      an H3 agonist (10(-8) M. to 10(-5) M.). The response to histamine was
      progressively attenuated by an H1 antagonist (mepyramine; 10(-8) M. to 10(-5)
      M.), while neither an H2 antagonist (cimetidine; 10(-4)M.) nor an H3 antagonist
      (thioperamide; 10(-4)M.) had any inhibitory effects. H1 antagonism enhanced
      relaxation induced by electrical field stimulation (neurally mediated). Such
      relaxation increased after preincubation with 10(-6) M. or greater of mepyramine
      (p < 0.05). This study suggests that the principal histamine receptor subtype
      that mediates smooth muscle cell contraction in the corpus cavernosum is the H1
      subtype. Since histamine H1 receptor antagonism increased NANC neurally mediated
      corporal relaxation, it possesses potential as an intracavernosal
      pharmacotherapeutic agent for the treatment of erectile dysfunction. This study,
      therefore, strongly indicates that H2 receptor antagonists are unlikely to have
      direct effects on penile erection.

PMID- 7815637
TI  - Hemodynamics of penile erection: III. Measurement of deep intracavernosal and
      subtunical blood flow and oxygen tension.
AB  - Previous studies have shown that intracavernosal blood flow increases during
      penile erection, but little is known about intracavernosal hemodynamics. Using a
      previously developed canine model of erection, we measured intracavernosal blood
      flow and oxygen tension at 2 sites within the corpus cavernosum: directly beneath
      the tunica albuginea and deep within the cavernous tissue. We chose to measure
      oxygen tension as an indicator of arterial blood flow. Penile erection was
      induced by pelvic nerve stimulation as well as by injection of papaverine and
      phentolamine. In the flaccid penis, blood flow measured directly under the tunica
      albuginea was significantly higher than deep intracavernosal blood flow.
      Subtunical oxygen tension in the flaccid penis was consistent with a largely
      arterial circulation. These observations provide physiological evidence of an
      important subtunical circulation that carries most of the intracavernosal blood
      flow when the penis is flaccid. With pelvic nerve stimulation, deep
      intracavernosal blood flow increased significantly followed by an increase in
      oxygen tension. Oxygen tension deep within the corpus cavernosum increased during
      penile erection from a level consistent with venous blood to a level consistent
      with arterial blood. Injection of papaverine and phentolamine caused a
      significant increase in intracavernosal pressure and a significant decrease in
      subtunical blood flow but did not cause statistically significant change in
      intracavernosal blood flow or oxygen tension. In contrast to nerve-induced
      erection, pharmacologically induced erection appears to depend more on
      intracavernosal shunting of blood than on increased total arterial blood flow to
      the penis. Hypogastric nerve stimulation during established erection caused
      detumescence by contracting cavernosal smooth muscle, reducing deep cavernosal
      blood flow and reestablishing blood flow through the subtunical space. Our
      observations suggest that the subtunical space contains an important circulation
      that may play a role in the hemodynamics of the flaccid, as well as the erect,
      penis.

PMID- 7815638
TI  - Antibiotic pharmacokinetics in the inflamed prostate.
AB  - We hypothesized that altered pharmacokinetics in the inflamed prostate gland
      might account for the treatment failure of clinically diagnosed chronic bacterial
      prostatitis. We employed a rat model of chronic bacterial prostatitis to
      investigate any pharmacokinetic differences that may exist between uninflamed and
      inflamed prostate glands. Four groups of animals were studied (treated and
      untreated control and prostatitis groups). Seven days of norfloxacin therapy
      cured 60% of the animals with well-established bacterial prostatitis compared
      with a spontaneous cure rate of 10% in the nontreated prostatitis animals.
      Norfloxacin levels did not change significantly between the infected and
      noninfected prostate glands. We conclude that failure of antibiotic therapy in
      chronic bacterial prostatitis is not due to significantly altered norfloxacin
      pharmacokinetics in the chronically inflamed prostate gland but rather to the
      difficulty of eradicating protected bacterial microcolonies within an infection
      induced altered microenvironment deep within the prostate gland.

PMID- 7815639
TI  - Investigation of the tissue effects of a new device for intracorporeal
      lithotripsy--the Swiss Lithoclast.
AB  - Currently three modalities are available for intracorporeal stone fragmentation-
      electrohydraulic, ultrasound and laser lithotripsy. A new device, the Swiss
      Lithoclast, has been developed by the Departments of Medical Electronics and
      Urology at the University of Lausanne, Switzerland. This device has been used
      clinically in several countries for the treatment of stones throughout the human
      urinary tract. While no adverse outcomes have been reported, the potential tissue
      effects of the device have not been thoroughly investigated in an animal model.
      The objective of the present study is to evaluate the possible acute and long
      term tissue effects of this instrument on the pig urinary tract. In all acute
      animals, visible mucosal lesions were seen at the site of probe firing in the
      bladders and ureters. Histologic examination demonstrated the effects of acute
      trauma with edema, hemorrhage and mucosal denudation. No significant long-term
      tissue effects were noted either pathologically or on radiographs in the 3- and 6
      week animals. This study confirms our clinical impression that the Swiss
      Lithoclast effectively fragments urinary calculi and is associated with a large
      margin of safety.

PMID- 7815640
TI  - Neoadjuvant chemotherapy for invasive bladder cancer: prognostic factors for
      survival of patients treated with M-VAC with 5 year follow-up.

PMID- 7815641
TI  - Value of repeated analyses of 24-hour urine in recurrent calcium urolithiasis.

PMID- 7815642
TI  - Radiologists display powerful new tools.

PMID- 7815644
TI  - From the Food and Drug Administration.

PMID- 7815643
TI  - Informing troops of investigational drugs, devices.

PMID- 7815645
TI  - From the Centers for Disease Control and Prevention. Hemorrhage and shock
      associated with invasive pneumococcal infection in healthy infants and children-
      New Mexico, 1993-1994.

PMID- 7815646
TI  - From the Centers for Disease Control and Prevention. Acute pulmonary
      hemorrhage/hemosiderosis among infants--Cleveland, January 1993-November 1994.

PMID- 7815647
TI  - From the Centers for Disease Control and Prevention. Update: respiratory
      syncytial virus activity--United States, 1994-95 season.

PMID- 7815648
TI  - The importance of placebo effects.

PMID- 7815649
TI  - The importance of placebo effects.

PMID- 7815650
TI  - HTLV-1 proviral DNA in oral aspirates of newborns born to seropositive mothers.

PMID- 7815651
TI  - Health system reform: will controlling cost require rationing services?

PMID- 7815652
TI  - Health system reform: will controlling cost require rationing services?

PMID- 7815653
TI  - Tuberculosis screening of applicants for US immigration.

PMID- 7815654
TI  - Prophylaxis against venous thromboembolism after hip surgery.

PMID- 7815655
TI  - Prophylaxis against venous thromboembolism after hip surgery.

PMID- 7815656
TI  - Health status and function with zidovudine or zalcitabine as initial therapy for
      AIDS. A randomized controlled trial. Roche 3300/ACTG 114 Study Group.
AB  - OBJECTIVE: To evaluate the functional and health status implications of
      prescribing zalcitabine or zidovudine for initial therapy of acquired
      immunodeficiency syndrome (AIDS). DESIGN: A substudy of a randomized controlled
      trial. SETTING: Private and public clinics and referral centers. PATIENTS: Had
      human immunodeficiency virus (HIV) infection, less than 0.20 x 10(9)/L (200
      microliters) CD4+ cells, and either a history of Pneumocystis carinii pneumonia
      or symptoms of HIV infection. Fifty-eight percent (338/668) of main study
      enrollees representing 90% of enrollees at participating sites were included in
      this substudy. INTERVENTIONS: Either zalcitabine at 0.75 mg every 8 hours plus
      inactive capsules identical in appearance to zidovudine or zidovudine at 200 mg
      (later 100 mg) every 4 hours plus inactive tablets identical in appearance to
      zalcitabine. MAIN OUTCOME MEASURES: Results of a periodically completed self
      report survey instrument containing specific questions about symptom impact,
      disability, work, functioning, and utilization as well as nine health and
      functioning scales adapted from the Medical Outcomes Study (MOS). RESULTS:
      Zalcitabine recipients were twice as likely to undergo an invasive procedure (P =
      .004) or be admitted to hospital (P = .01). Zalcitabine recipients reported
      greater than 40% more symptoms that interfered with activity (P = .001) and
      greater than 50% more disability days (P < .01). They also had a 7% lower
      employment rate and a 35% lower monthly income. Average observed health status
      scores were lower in zalcitabine recipients overall, but especially in the early
      portion of the study. New methods for combining survival and health status data
      showed that, over 76 weeks of study, a typical zidovudine recipient spent about 4
      (10%) more weeks with at least the typical health state than did a typical
      zalcitabine recipient. CONCLUSIONS: Zidovudine has substantial advantages over
      zalcitabine in initial monotherapy of AIDS in terms of functional outcomes such
      as symptoms impact, disability, work, utilization, and health status. In this
      case, the differences in functional outcomes presaged differences in
      physiological and clinical measures. The inclusion of functional outcomes can
      greatly improve the information available from a clinical trial.

PMID- 7815657
TI  - Medical decision making in situations that offer multiple alternatives.
AB  - OBJECTIVE: To determine whether situations involving multiple options can
      paradoxically influence people to choose an option that would have been declined
      if fewer options were available. DESIGN: Mailed survey containing medical
      scenarios formulated in one of two versions. PARTICIPANTS: Two groups of
      physicians: members of the Ontario College of Family Physicians (response rate =
      77%; n = 287) and neurologists and neurosurgeons affiliated with the North
      American Symptomatic Carotid Endarterectomy Trial (response rate = 84%; n = 352).
      One group of legislators belonging to the Ontario Provincial Parliament (response
      rate = 32%; n = 41). INTERVENTION: The basic version of each scenario presented a
      choice between two options. The expanded version presented three options: the
      original two plus a third. The two versions otherwise contained identical
      information and were randomly assigned. OUTCOME MEASURES: Participants treatment
      recommendations. RESULTS: In one scenario involving a patient with
      osteoarthritis, family physicians were less likely to prescribe a medication when
      deciding between two medications than when deciding about only one medication
      (53% vs 72%; P < .005). Apparently, the difficulty in deciding between the two
      medications led some physicians to recommend not starting either. Similar
      discrepancies were found in decisions made by neurologists and neurosurgeons
      concerning carotid artery surgery and by legislators concerning hospital
      closures. CONCLUSIONS: The introduction of additional options can increase
      decision difficulty and, hence, the tendency to choose a distinctive option or
      maintain the status quo. Awareness of this cognitive bias may lead to improved
      decision making in complex medical situations.

PMID- 7815658
TI  - Improved survival of patients with acute respiratory distress syndrome (ARDS):
      1983-1993.
AB  - OBJECTIVE: To analyze temporal trends in acute respiratory distress syndrome
      (ARDS) fatality rates since 1983 at one institution. DESIGN: Cohort. SETTING:
      Intensive care units of a large county hospital. PATIENTS: Consecutive adult
      patients (> or = 18 years of age) meeting ARDS criteria were identified through
      daily surveillance of intensive care units (N = 918 from 1983 through 1993). The
      major causes were sepsis syndrome in 37% and major trauma in 25%; 37% had other
      risks. Sixty-five percent were male. The median age was 45 years (range, 18 to 92
      years); 70% were younger than 60 years. MAIN OUTCOME MEASURE: Hospital mortality.
      RESULTS: Overall fatality rates showed no trend from 1983 to 1987, declined
      slightly in 1988 and 1989, and decreased to a low of 36% in 1993 (95% confidence
      interval, 25% to 46%). The crude rates were largely unchanged after adjustment
      for age, ARDS risk, and gender distribution. While patients both younger than 60
      years and 60 years or older experienced declines in fatality rate, the larger
      decrease occurred in the younger cohort. In sepsis patients, ARDS fatality rates
      declined steadily, from 67% in 1990 to 40% in 1993 (95% confidence interval, 23%
      to 57%). The decline in sepsis-related ARDS fatality was confined largely to
      patients less than 60 years of age. Trauma patients and all other patients also
      experienced declines in fatality rates after 1987, although these trends were not
      as strong and consistent as in the sepsis population. CONCLUSIONS: In this large
      series, we observed a significant decrease in fatality rates occurring largely in
      patients younger than 60 years and in those with sepsis syndrome as their risk
      for ARDS. We are unable to determine the extent to which experimental therapies
      or other changes in treatment have contributed to the observed decline in the
      ARDS fatality rate. Institution-specific rates and temporal trends in ARDS
      fatality rates should be considered in clinical trials designed to prevent ARDS
      and the high mortality associated with this syndrome.

PMID- 7815659
TI  - Requesting consent for an invasive procedure in newly deceased adults.
AB  - OBJECTIVE: Ethical concerns exist over the performance of medical procedures,
      such as endotracheal intubation, on newly deceased patients without family
      consent. This study examined the process of obtaining consent for the purpose of
      performing an invasive procedure in newly deceased adults. DESIGN: A prospective
      case series. PARTICIPANTS: The families of patients who died during a 5-month
      period were requested to provide consent to perform wire-guided retrograde
      tracheal intubation. MAIN OUTCOME MEASURES: Differences between success and
      failure in obtaining consent including information on the decreased, family
      reasons for their decision, and the experience of those requesting consent.
      RESULTS: Consent was requested from 44 families and 26 (59%) agreed to the
      procedure. This success rate was achieved despite the lack of a prior
      relationship with the family by the persons requesting consent. Consent was
      obtained more frequently in unexpected than expected deaths (77% vs 41%, P =
      .03). There were no differences in success rates for consent for age, race, sex,
      or do-not-resuscitate status of the deceased. Spouses consented more frequently
      than children (77% vs 50%, P = .25). The two physicians reported greater comfort
      in requesting consent than the nurse anesthetist investigator. In one instance,
      the consent process may have increased the emotional distress of the family.
      CONCLUSION: Consent can frequently be obtained from families for an invasive
      procedure in newly deceased adults. Physicians should reconsider the practice of
      performing postmortem procedures without obtaining family consent.

PMID- 7815660
TI  - Does the clinical examination predict airflow limitation?

PMID- 7815661
TI  - Educational resource sharing and collaborative training in family practice and
      internal medicine. A statement from the American Boards of Internal Medicine and
      Family Practice.

PMID- 7815662
TI  - Preserving the physician-patient relationship in the era of managed care.
AB  - Even without comprehensive health care reform legislation, the US health care
      system is undergoing significant changes. Probably the most important change is
      the expansion of managed care with significant price competition. One of the
      major concerns about this change is the effect of managed care on the physician
      patient relationship. To provide a normative standard for evaluating the effect
      of changes, we need an ideal conception of the physician-patient relationship.
      This ideal can be summarized by six C's: choice, competence, communication,
      compassion, continuity, and (no) conflict of interest. For the 37 million
      uninsured Americans there is little chance of realizing the ideal physician
      patient relationship, since they lack the choice of practice setting and
      physician, receive care in a rushed atmosphere that undermines communication and
      compassion, and have no continuity of care. While many insured Americans may
      believe they have an ideal physician-patient relationship, the relationship is
      threatened by lack of a regular assessment of competence, by financial incentives
      that undermine good communication, and by the persistence of conflict of
      interest. The shift to managed care may improve the choice of practice settings,
      especially in sections of the country that currently lack managed care; increase
      choice of preventive services; make quality assessments more routine; and improve
      communication by making greater use of primary care physicians and nonphysician
      providers. However, the expansion of managed care and the imposition of
      significant cost control have the potential to undermine all aspects of the ideal
      physician-patient relationship. Choice could be restricted by employers and by
      managed care selection of physicians; poor quality indicators could undermine
      assessments of competence; conductivity requirements could eliminate time
      necessary for communication; changing from one to another managed care plan to
      secure the lowest costs could produce significant disruption in continuity of
      care; and use of salary schemes that reward physicians for not using medical
      services could increase conflict of interest.

PMID- 7815663
TI  - Ethical issues in managed care.

PMID- 7815664
TI  - Managed care. Jekyll or Hyde?

PMID- 7815665
TI  - A piece of my mind. A mutual investment company.

PMID- 7815666
TI  - How white and African Americans view their health and social problems. Different
      experiences, different expectations.

PMID- 7815667
TI  - Jonathan E. Rhoads Lecture. Medicine, nutrition, and patient care: a panoramic
      view.

PMID- 7815668
TI  - Metabolic effects of long-chain and medium-chain triglyceride emulsions in
      humans.

PMID- 7815669
TI  - Correlation between measured energy expenditure and clinically obtained variables
      in trauma and sepsis patients.
AB  - BACKGROUND: Indirect calorimetry is the preferred method for determining caloric
      requirements of patients, but availability of the device is limited by high cost.
      A study was therefore conducted to determine whether clinically obtainable
      variables could be used to predict metabolic rate. METHODS: Patients with severe
      trauma or sepsis who required mechanical ventilation were measured by an open
      circuit indirect calorimeter. Several clinical variables were obtained
      simultaneously. Measurements were repeated every 12 hours for up to 10 days.
      RESULTS: Twenty-six trauma and 30 sepsis patients were measured 423 times. Mean
      resting energy expenditure was 36 +/- 7 kcal/kg (trauma) vs 45 +/- 8 kcal/kg
      (sepsis) (p < .0001). The single strongest correlate with resting energy
      expenditure was minute ventilation (R2 = 0.61, p < .0001). Doses of dopamine,
      dobutamine, morphine, fentanyl, and neuromuscular blocking agents each correlated
      positively with resting energy expenditure. In the case of the inotropics and
      neuromuscular blockers, there was a probable covariance with severity of illness.
      A multiple regression equation was developed using minute ventilation, predicted
      basal energy expenditure, and the presence or absence of sepsis: resting energy
      expenditure = -11000 + minute ventilation (100) + basal energy expenditure (1.5)
      + dobutamine dose (40) + body temperature (250) + diagnosis of sepsis (300) (R2 =
      0.77, p < .0001). CONCLUSION: Severe trauma and sepsis patients are
      hypermetabolic, but energy expenditure is predictable from clinical data. The
      regression equations probably apply only to severe trauma and sepsis. Other
      studies should be conducted to predict energy expenditure in other patient types.

PMID- 7815670
TI  - Amino acid solutions for premature neonates during the first week of life: the
      role of N-acetyl-L-cysteine and N-acetyl-L-tyrosine.
AB  - Tyrosine and cyst(e)ine are amino acids that are thought to be essential for
      preterm neonates. These amino acids have low stability (cyst(e)ine) or low
      solubility (tyrosine) and are therefore usually present only in small amounts in
      amino acid solutions. Acetylation improves the stability and solubility of amino
      acids, facilitating a higher concentration in the solution. We compared three
      commercially available amino acid solutions, Aminovenos-N-pad 10%, Vaminolact
      6.5%, and Primene 10%, administered to 20 low-birth-weight neonates on total
      parenteral nutrition from postnatal day 2 onward. Aminovenos-N-pad 10% contains
      acetylated tyrosine and acetylated cysteine; the other solutions do not contain
      acetylated amino acids and differ in the amount of tyrosine and cysteine added.
      On postnatal day 7, plasma amino acids were measured together with urinary
      excretion of amino acids and the total nitrogen excretion; 38% of the intake of N
      acetyl-L-tyrosine and 53% of the intake of N-acetyl-L-cysteine were excreted in
      urine. Plasma levels of N-acetyl-L-tyrosine (331 +/- 74 mumol/L) and N-acetyl-L
      cysteine (18 +/- 29 mumol/L) were higher than those of tyrosine (105 +/- 108
      mumol/L) and cystine (11 +/- 9 mumol/L), respectively. Plasma tyrosine levels in
      the groups receiving small amounts of tyrosine remained just below the reference
      range. We show a linear correlation of plasma cystine with the intake of cysteine
      (r = .75, p = 0.01), but not with N-acetyl-L-cysteine. The estimated intake of
      cysteine should be 500 mumol.kg-1.d-1 in order to obtain levels comparable with
      those shown in normal term, breast-fed neonates. Nitrogen retention did not
      differ among the three groups (247 to 273 mg.kg-1.d-1).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7815672
TI  - Immunoregulation by parenteral lipids: impact of the n-3 to n-6 fatty acid ratio.
AB  - BACKGROUND: The immune system is reported to be influenced by polyunsaturated
      fatty acids. Therefore, immunoregulation caused by intravenous fat emulsions with
      different n-3 to n-6 fatty acid ratios was studied in an in vivo model. METHODS:
      Experimental rat heart allotransplantation served as a defined immunologic
      challenge. Twenty percent emulsions of safflower oil (n-3 to n-6 = 1:370), fish
      oil (n-3 to n-6 = 7.6:1), and soybean oil (n-3 to n-6 = 1:6.5), and a 1:1 mixture
      of safflower oil and fish oil (n-3 to n-6 = 1:2.1) were continuously infused (9 g
      of fat per kg of body weight per day) after transplantation until complete
      rejection. The prolongation of graft survival, an accepted parameter of
      immunosuppression, was assessed. Beyond that, cytokine release by mitogen
      stimulated peripheral-blood mononuclear cells (PBMCs) from animals exsanguinated
      on day 4 after transplantation was evaluated. RESULTS: The mean rejection time
      was 7.8 days in the sham-infused saline control group and 6.7 days in the
      safflower- and fish-oil-mixture group (oil control group). Continuous infusion of
      soybean oil prolonged the graft survival time to 10.4 days, fish oil to 12.3
      days, and safflower oil to 13.3 days. PBMC alpha-tumor necrosis factor release
      was significantly reduced in the fish-oil group (51.9 +/- 13.0 pg/10(6) PBMCs vs
      70.8 +/- 10.9 pg/10(6) PBMCs [controls], p < .004). Interleukin-6 release was
      diminished in both the fish-oil group (22.2 +/- 13.6 pg/10(6) PBMCs vs 40.7 +/-
      8.3 pg/10(6) PBMCs [controls], p < .002) and the safflower-oil group (28.4 +/-
      6.9 pg/10(6) PBMCs, p < .002). CONCLUSIONS: The n-3 to n-6 fatty acid ratio
      determined the immunoregulatory potential of intravenous fat emulsions in vivo.
      Both n-3 and n-6 fatty acids were immunosuppressive when applied as the main
      polyunsaturated fatty acid sources. PBMC cytokine release was significantly
      reduced in these groups. The more balanced the n-3 to n-6 ratios, the less
      immunosuppressive the fat emulsion. There was no immunosuppressive effect at an n
      3 to n-6 ratio of 1:2.1.

PMID- 7815671
TI  - Cardiac cachexia: preoperative and postoperative nutrition management.
AB  - The present study examined the hemodynamic and metabolic effects of nutrition
      support in patients with malnutrition secondary to severe mitral valve disease
      and congestive heart failure. Pulmonary artery pressure measurements,
      echocardiographic studies, gas exchange measurements, immune function tests, and
      clinical evaluations were made on hospitalized patients 2 weeks before and 3
      weeks after surgery for valve replacement or annuloplasty. All patients received
      a total daily energy intake of 20 to 30 kcal/kg, four of the patients
      preoperatively as a combination of oral food plus parenteral nutrition and these
      four patients plus two additional patients as only parenteral nutrition in the
      early postoperative period. All six patients received nutrition support as oral
      food plus parenteral nutrition in the late postoperative period. Compared with
      baseline, nutrition support was associated with stable hemodynamic function,
      unchanged whole-body oxygen consumption and carbon dioxide production, and
      improved clinical indices both before and after surgery. Comprehensive
      hemodynamic, metabolic, and clinical studies thus indicate that acceptable levels
      of nutrition support can be provided to malnourished patients with severe
      congestive heart failure, which improves their clinical status and does not
      adversely influence cardiac function.

PMID- 7815673
TI  - Glutamine-enriched enteral diet increases renal arginine production.
AB  - BACKGROUND: Arginine (Arg) is generated in the kidney by the conversion of
      circulating citrulline. The most important source for circulating citrulline is
      the metabolism of glutamine (Gln) by the gut. In this study, we investigated the
      influence of an enteral diet enriched with Gln on renal Arg synthesis in the rat.
      METHODS: Rats were fed a 12.5% Gln-enriched diet or an isocaloric, isonitrogenous
      control diet for 14 days. Kidney plasma flow and arterial and renal venous plasma
      levels of a number of amino acids were measured, and kidney amino acid fluxes
      were calculated. RESULTS: Compared with the control diet, Gln enrichment resulted
      in significantly higher arterial plasma levels of circulating citrulline (30%, p
      < .0001) and Arg (31%, p < .0005). The uptake of circulating citrulline and the
      subsequent production of Arg by the kidneys were significantly higher in the Gln
      enriched group (40% and 38%, respectively) and showed an equimolar relationship
      in both the control (r = .84, p < .0001) and the Gln-enriched group (r = .83, p <
      .0001). CONCLUSIONS: The findings indicate that enteral Gln supplementation
      caused significantly increased arterial plasma levels of Arg as a result of
      increased renal Arg production from circulating citrulline. Considering the
      multiple important biologic properties of Arg, the reported beneficial effects of
      Gln in catabolic states might be explained in part by increased renal Arg
      production.

PMID- 7815674
TI  - Assessment of body composition by skinfold anthropometry and bioelectrical
      impedance technique: a comparative study.
AB  - Both skinfold anthropometry and bioelectrical impedance are indirect, simple
      bedside methods to assess body composition. It is not clear, however, whether the
      results of these methods are comparable. In this study, body composition was
      determined in 449 subjects by skinfold anthropometry and by bioelectrical
      impedance. Percentage of body fat ranged from 8.0% to 47.5% with the skinfold
      technique and from 0.6% to 78.5% with bioelectrical impedance. Linear regression
      analysis showed a significant positive correlation (r = .84; p < .0001) between
      the results of both techniques. However, plot analysis showed that, in comparison
      with bioelectrical impedance, skinfold measurements overestimate fat mass in the
      lower weight range and underestimate it in obese subjects. We conclude that the
      results of skinfold anthropometry and bioelectrical impedance are not comparable,
      especially in the extreme ranges of body fat. At the present time, other, more
      rigorous techniques are necessary to assess body composition accurately, in the
      extreme ranges of body fat in particular.

PMID- 7815675
TI  - Bioavailability of magnesium diglycinate vs magnesium oxide in patients with
      ileal resection.
AB  - BACKGROUND: Patients who have undergone ileal resection are at risk for
      developing magnesium depletion/deficiency because of poor absorption and
      decreased intake as well as increased endogenous losses. Magnesium repletion is
      difficult to accomplish because of the cathartic action of most oral magnesium
      supplements at therapeutic doses. The results of in vitro and in situ studies
      show that magnesium diglycinate (chelate) represents a highly available form of
      magnesium that is absorbed in part as an intact dipeptide in the proximal small
      intestine. METHODS: We conducted a double-blind, randomized crossover trial with
      12 patients who had ileal resections in order to compare the bioavailability of a
      100-mg dose of 26Mg-labeled chelate with MgO in this patient population. RESULTS:
      For the patient group as a whole, 26Mg absorption was low but was not different
      for the two supplements (23.5% vs 22.8% for magnesium chelate and MgO,
      respectively). However, 26Mg absorption was substantially greater from the
      chelate (23.5% vs 11.8%; p < .05) in the four patients who showed the greatest
      impairment of magnesium absorption with MgO and was better tolerated by all
      patients. Peak isotope enrichment also occurred significantly earlier after 26Mg
      chelate than after 26MgO ingestion (mean difference 3.2 +/- 1.3 hours; p < .05),
      and the area under the enrichment vs time curve was greater after chelate
      ingestion (p < .05). CONCLUSIONS: Data from this study support the suggestion
      that some portion of magnesium diglycinate is absorbed intact, probably via a
      dipeptide transport pathway. Magnesium diglycinate may be a good alternative to
      commonly used magnesium supplements in patients with intestinal resection.

PMID- 7815676
TI  - Infusion of long-chain or medium-chain triglycerides inhibits peripheral glucose
      metabolism in men.
AB  - To investigate whether increased availability of lipids affects glucose
      metabolism in healthy postabsorptive men when lipid and glucose are infused in
      amounts used in parenteral nutrition, we infused glucose (4 mg/kg.min-1) for 6
      hours and clamped plasma glucose at basal level during the first 3 hours. After 3
      hours, either long-chain triglycerides (LCTs) (0.07 g/kg.h-1) (n = 7) or a
      mixture of LCTs and medium-chain triglycerides (MCTs) (MCTs/LCTs, 50/50%, 0.07
      g/kg.h-1) (n = 7) was administered, and the infusion rates of glucose and insulin
      were unchanged compared with the first 3 hours. In a control study, glucose was
      infused for a period of 6 hours without the lipid infusion (n = 5). After 6
      hours, the plasma glucose concentration and glucose tissue uptake were not
      affected by LCT or MCT/LCT infusion. Nonetheless, glucose oxidation decreased in
      the LCT group (from 6.42 +/- 1.04 to 2.31 +/- 0.85 mumol/kg.min-1, p < .001) and
      in the MCT/LCT group (from 7.62 +/- 1.50 to 5.50 +/- 0.76 mumol/kg.min-1, p <
      .01) but not in the control group. Concentrations of the glucoregulatory hormones
      were not different among the three groups. In conclusion, MCTs/LCTs administered
      concomitantly with glucose infusion, in amounts similar to those used in total
      parenteral nutrition, inhibit glucose oxidation without affecting glucose tissue
      uptake, just as LCTs do.

PMID- 7815677
TI  - Effect of ketone bodies on hyperglycemia and lactic acidemia in hemorrhagic
      stress.
AB  - BACKGROUND: To investigate the effect of hyperketonemia on altered glucose
      metabolism under stress conditions, we infused sodium D-3-hydroxybutyrate (3-OHB)
      into rats in hemorrhagic hypotension and evaluated the plasma concentration of
      substrates related to glucose metabolism. METHODS: Three groups of anesthetized
      rats (weight, 280 g to 320 g) were bled acutely, and their mean arterial
      pressures were maintained at 40 mm Hg. From 1 hour before hemorrhage to the end
      of the experiment, rats in the first group (n = 10) were infused with 3-OHB at a
      rate of 30 mumol/kg.min (3-OHB group), those in the second group (n = 10)
      received glucose and sodium bicarbonate (glucose group), and the remaining 10
      rats received only sodium bicarbonate and no energy substrates (control group).
      Sodium bicarbonate was used to control the alkalizing effect of 3-OHB. RESULTS:
      Hyperketonemia (1158 +/- 30 mumol/L - 1618 +/- 154 mumol/L) occurred only in the
      3-OHB group. Hyperglycemia and lactic acidemia during hemorrhagic shock were
      suppressed significantly compared with the control group. Plasma concentration of
      alanine was also lower compared with the control group. In the glucose group,
      although plasma lactate concentration was lower, plasma glucose concentration was
      not suppressed, and plasma alanine concentration was higher in comparison with
      the control group during hemorrhagic shock. There was no significant difference
      in plasma insulin concentration among the three groups. CONCLUSIONS: These
      results suggest that administered 3-OHB may suppress glycolysis during
      hemorrhagic shock.

PMID- 7815678
TI  - Comparison of intravenous nutrients on gut mucosal proteins synthesis.
AB  - BACKGROUND: Total parenteral nutrition (TPN) is associated with atrophy of the
      intestinal mucosa. This study compared the relative effectiveness of a short
      chain fatty acid (butyrate), a physical mixture of medium-chain and long-chain
      triglycerides, structured lipid, and glutamine as components of a TPN regimen,
      and their ability to support mucosal protein synthesis. METHODS: Rats were
      parenterally fed one of six isocaloric (1003 kJ/kg.d-1) and isonitrogenous (1.5
      g.kg-1.d-1 of nitrogen) diets for 5 days. Diet 1, glucose 90% and long-chain
      triglycerides 10% (standard TPN); diet 2, glucose 50% and long-chain
      triglycerides 50%; diet 3, glucose 50% and a 50/50 physical mixture of long-chain
      and medium-chain triglycerides 50%; diet 4, glucose 50% and structured lipid 50%;
      diet 5, glucose 91% and sodium butyrate 9%; and diet 6, same as group 1 except
      that some of the amino acids were replaced with glycyl glutamine. A control group
      of rats also underwent catheter placement and were instead fed diet 1 orally for
      5 days. Five days after catheterization, all rats were given a 4-hour constant
      infusion of [U-14C]leucine to determine the mucosal fractional protein synthesis
      rates. RESULTS: (1) Mucosal fractional protein synthesis rates were much higher
      with the oral diet (control) than with any of the intravenous diets. (2) Diet
      related differences in the mucosal fractional synthesis rates were found with the
      jejunum and the proximal and distal colon but not with the ileum. (3) Standard
      TPN was the least effective diet in supporting mucosal protein synthesis. (4)
      Structured lipid and butyrate were most effective for the jejunum. (5) For the
      colon, medium-chain triglycerides and structured lipid were most effective.
      CONCLUSION: Standard TPN leads to a decrease in gut mucosal protein synthesis in
      rats, and this decrease can be partially attenuated by adding nutrients for the
      gut to the TPN mixture.

PMID- 7815679
TI  - Evaluation of "closed" vs "open" systems for the delivery of peptide-based
      enteral diets.
AB  - BACKGROUND: The study was designed to quantitate factors such as preparation
      time, waste, and contamination associated with three different feeding systems
      for peptide-based diets and to determine appropriate hang times. METHODS:
      Intensive care unit patients were randomized to receive a peptide-based diet in
      1500-mL prefilled, sterile closed-system containers (CS) infused more than 24
      hours, as open systems decanted from cans (OS-Can), or as open systems mixed from
      powder (OS-Powder). Open-system groups were provided a 12-hour supply twice daily
      in commercially clean 1-L bags with preattached sets. Samples were taken for
      culture during preparation and after infusion. Preparation time, initial and
      final microbial concentrations, and total waste were quantified. RESULTS:
      Preparation time was significantly shorter for CS than for OS-Can or for OS
      Powder (2 minutes vs 7.5 minutes vs 13.0 minutes). Initially, 100% of the OS
      Powder and 30% of the OS-Can bags were contaminated, with significant
      contamination exceeding 10(4) colony-forming units/mL in 40% and in 5% of the
      bags, respectively. On final culture, significant contamination occurred in only
      2% of the CS bags compared with 83% of the OS-Powder and 60% of the OS-Can bags.
      Average time from potential initial contamination to final culture in CS was 49.9
      hours vs 38.8 hours for OS-Can and 32 hours for OS-Powder. Total waste was
      greater in CS than in OS-Can or OS-Powder but could be eliminated by extending
      allowable hang times. CONCLUSIONS: Nonvented closed-delivery containers may be
      safely infused for up to 48 hours. They are associated with reduced labor and
      contamination.

PMID- 7815680
TI  - The effect of parenteral nutrition on hepatic cytochrome P-450.
AB  - BACKGROUND: Total parenteral nutrition (TPN) has been shown to affect liver
      function tests. Additional investigations in animals and humans have demonstrated
      that hepatic cytochrome P-450 content and enzyme activity are also affected.
      METHODS: To review the literature on the effect of TPN on hepatic cytochrome P
      450, an English-language literature search was performed using MEDLINE (1966
      through 1993). RESULTS: Studies in laboratory rats show that administration of
      dextrose, with or without amino acids, decreases the cytochrome P-450 content and
      the in vitro or in vivo microsomal oxidation rates of various drugs. The addition
      of lipid emulsions to TPN decreases oxidation rates for meperidine demethylase
      but does not affect ethoxyresorufin deethylase. Using immunoquantitation, it was
      shown that the components of TPN selectively affect specific hepatic P-450
      enzymes. In humans, dextrose decreases antipyrine clearance, whereas amino acids
      and possibly lipids increase antipyrine clearance. However, the effects of
      protein-calorie malnutrition in these studies obscure the results. CONCLUSIONS:
      Possible mechanisms for the reduction of hepatic cytochrome P-450 seen during TPN
      administration include altered gastrointestinal hormone response, mucosal
      barrier, and the effect of sepsis. Additional studies are needed to determine the
      actual mechanisms of hepatic cytochrome P-450 reduction observed during TPN.

PMID- 7815682
TI  - Dietary fish oil supplementation attenuates myocardial dysfunction and injury
      caused by global ischemia and reperfusion in isolated rat hearts.

PMID- 7815681
TI  - Percutaneous adipose tissue biopsy by mini-liposuction for metabolic studies.
AB  - BACKGROUND: Large fat-biopsy samples are necessary for extensive simultaneous
      assays. Subcutaneous adipose tissue is generally obtained either by needle-biopsy
      aspiration (approximately 1 g) or by open surgical biopsy for larger samples. We
      propose a reliable technique that permits the removal of large adipose tissue
      samples percutaneously. METHODS: A vertical 5-mm slit was made in the abdominal
      skin of 15 obese patients, and a liposuction mini-cannula (10 cm x 3 mm) attached
      to a 20-mL sterile plastic syringe was inserted. A vacuum was created by
      withdrawing the syringe plunger and fixing it with a specially adapted clamp.
      RESULTS: We obtained 3- to 15-g samples of adipose tissue without conspicuous
      scarring or visible contour changes. A significant correlation between the body
      mass index and the amount of adipose tissue was observed (r = .50, p < .05).
      Isolated adipocytes remained highly viable, as evidenced by glucose transport
      under both basal and maximal insulin-stimulated conditions. The mini-liposuction
      procedure was fast, and once the mini-cannula was removed from the wound,
      patients could immediately move about freely. CONCLUSION: The new technique
      described here for fat biopsy using a mini-cannula is less traumatic than open
      surgical biopsy, and it permits the removal of larger adipose tissue samples than
      do the usual biopsy techniques. Furthermore, adipose cells are removed intact,
      and the simplicity of the method facilitates repeat biopsies.

PMID- 7815683
TI  - Treatment of hepatitis C with interferons: a need for caution.

PMID- 7815684
TI  - Inherited metabolic disorders in Pakistan: presentation, diagnosis and outcome of
      congenital hyperammonemias.
AB  - A total of 21 patients were admitted to Aga Khan University Hospital with
      suspected congenital hyperammonemias during the period 1989 to 1992. There were
      11 patients with acidosis and 10 patients were without acidosis. Prominent
      clinical manifestations included positive family history (76%), onset in the
      first week of life (67%) and neurological manifestations (76%). Of patients with
      hyperammonemia and acidosis, 4 had severe metabolic acidosis with anion gap of
      30mEq/L and above. Of patients with hyperammonemia without acidosis, 4 had
      ammonia level ranging from 1600-2000 mg/dl. Diagnosis was confirmed in only 1
      patient and that was also done abroad. Overall mortality was 71%. In conclusion,
      these disorders are not uncommon in our country and should be suspected in all
      infants with above clinical or biochemical abnormalities.

PMID- 7815685
TI  - Interaction of chlorpromazine with tricyclic anti-depressants in schizophrenic
      patients.
AB  - Interaction of Chlorpromazine with tricyclic antidepressants was investigated in
      twenty schizophrenic patients after their concurrent administration. A
      significant increase in serum chlorpromazine concentration was observed when
      administered in combination with both amitriptyline and imipramine with
      chlorpromazine. If combined therapy is indicated, the dose of chlorpromazine
      should be reduced or the time of administration of other two drugs should be
      adjusted to maintain therapeutic levels of chlorpromazine.

PMID- 7815686
TI  - Pathological profile in chronic suppurative otitis media--the regional
      experience.
AB  - Peroperative findings in 145 consecutive cases of chronic suppurative otitis
      media, operated at Civil Hospital, Karachi were recorded. The mean age was 24
      years. More than half of the patients (51%) had subtotal perforations and
      majority had damage of more than one ossicle. Involvement of all the three
      ossicles was seen in 30 (40%) cases. The frequency of damaged malleus along with
      incus was higher than other series. Granulations and subtotal perforations were
      commoner and could account for it. Extensive cholesteatoma was present in 30
      cases.

PMID- 7815687
TI  - Safety of pharmacological (intravenous dipyridamole) stress for Thallium-201
      perfusion imaging in patients with coronary artery disease unable to exercise.
AB  - Exercise Thallium-201 myocardial perfusion imaging is a sensitive technique for
      detection of CAD. However, in patients unable to perform exercise pharmacological
      stress with intravenous dipyridamole can be used to dilate coronaries. Out of 125
      patients (21 men and 104 women; mean age 52.03 years) evaluated, 110 were
      considered to be unable to perform adequate stress by their physician while
      remaining 15 had LBBB. One hundred and seven patients had chest pain with or
      without a remote MI while 18 individuals were clinically asymptomatic but had ECG
      abnormalities. Intravenous dipyridamole was administered at a rate of 0.142
      mg/kg/min for 4 min. After 3 min an i.v. bolus of T1-201 was given. Diffuse or
      occipital headache of mild to moderate intensity occurred in 50 (40%) cases; 39
      patients experienced chest pain and had either a positive thallium scan (26
      cases) suggestive of CAD or a normal thallium study (15 cases). Complete relief
      from dipyridamole induced symptoms was brought by i.v. aminophylline and
      sublingual nitrate in 51 of 54 cases (94%) and 11 of 18 (61%) respectively. We,
      therefore, conclude: 1) i.v. dipyridamole-thallium scintigraphy offers a safe,
      effective and reliable method for evaluating CAD in those who are unable to
      perform adequate exercise and 2) parenteral aminophylline is very effective
      antidote to dipyridamole.

PMID- 7815688
TI  - Screening for chronic lead poisoning in lead factory workers.
AB  - One hundred and forty-nine lead factory workers comprising of 46 fume exposed, 78
      handling lead materials and 25 controls were screened for chronic lead poisoning.
      Blood lead level was determined by atomic absorption spectrometery and urinary
      ALA by ion-exchange chromatography. Fume exposed workers had significantly higher
      (P < 0.01) blood lead (median 61.20 micrograms/dl, range 21.20-171.10
      micrograms/dl) and urinary ALA levels (median 4.10 mg/l, range 01.0-22.9 mg/l)
      than workers handling lead materials and controls. Urinary ALA was found to be a
      more sensitive and specific test for lead poisoning than estimation of blood lead
      levels.

PMID- 7815689
TI  - Anterolateral decompression for traumatic spinal cord compression.
AB  - Nine patients with traumatic fractures of dorsolumbar spine leading to pain and
      neurological deficit are presented. All had radiological evidence of spinal cord
      or quada equina compression, with either monoparesis, paraparesis or sphincter
      dysfunction alone. All patients underwent anterolateral decompression through a
      transpleural or retroperitoneal approach. Seven patients had bone grafting and
      spinal stabilization with Webb-Morley system. Two patients had decompression
      only. The results were favourable. This approach is safe and effective and allows
      early mobilization and functional recovery.

PMID- 7815690
TI  - Post-anaesthetic pulmonary oedema following upper airway obstruction.
AB  - Twelve cases of post-anaesthetic pulmonary oedema (PO) secondary to upper airway
      obstruction (UAO) are reported. All were adult male patients undergoing
      uneventful elective surgical procedure under general anaesthesia. Post
      anaesthetic laryngospasm was the single most important factor for the upper
      airway obstruction (UAO) in 5 (41.6%) patients. PO secondary to partial UAO in
      drowsy patients was observed in 4 (33.3%) patients. UAO due to foreign body was
      responsible for PO in two patients. A combination of negative intrathoracic
      pressure, hypoxia and associated hyperadrenergic state were the most likely
      causes of PO in these patients with UAO. Early recognition, maintenance of patent
      airway and adequate oxygenation via face mask or endotracheal tube with
      mechanical ventilation resolved the syndrome within 6-36 hours in all of these
      patients. Invasive haemodynamic monitoring or aggressive drug therapy were not
      applied in any of the patients. A heightened awareness among anaesthesiologists
      of the varied causes of post-anaesthetic UAO leading to PO may help reduce the
      occurrence and facilitate early management of the potential complications.

PMID- 7815691
TI  - Correct use of incidence and prevalence.

PMID- 7815692
TI  - [The action of non-depolarizing muscle relaxants on nerve terminal of motor
      endplate--relationship between run-down of endplate potentials and fading tension
      response].
AB  - The classical view of the neuromuscular transmission is that non-depolarizing
      muscle relaxants (MRs) enhance run-down of the endplate potentials (epps) by
      blocking pre-junctional nicotinic acetylcholine (ACh) receptors. Several recent
      investigations, when extended to pharmacology, have provided evidence to suggest
      the existence of other types of enhancement of run-down of epps by MRs; the
      enhancement of epps occurs without reduction of ACh release in the presence of
      MRs. It has been generally accepted that the enhancement of run-down of epps
      causes the tetanic fade of tension response. However, recent evidence indicates
      that run-down of epps does not always cause this wane in tension. The
      electrophysiological mechanism of run-down of epps at the neuromuscular junction
      and the relationship between that phenomenon and the extent of reduction of
      tension response are described based on a review of literature and our current
      investigations.

PMID- 7815693
TI  - [Periodical blood pressure variation during cardiopulmonary bypass--effects of
      cervicothoracic epidural anesthesia and phentolamine].
AB  - We studied the effects of cervicothoracic epidural anesthesia or intravenous
      phentolamine on periodical blood pressure variation during cardiopulmonary bypass
      in 12 adult patients undergoing open heart surgery under fentanyl anesthesia.
      Spontaneous periodical fluctuation of the blood pressure was analyzed by means of
      autoregressive power spectrum method. Amplitudes of the low frequency (0.02-0.15
      Hz) component of the blood pressure variation amplitudes were calculated. The
      amplitudes decreased significantly 10 minutes after cervicothoracic epidural
      block with 15 ml of 2% lidocaine solution (P < 0.05), and after infusion of 0.4
      mg.kg-1 of phentolamine (P < 0.05). Since amplitudes of the blood pressure
      variation were reduced by adequate epidural block or phentolamine, they are
      likely to reflect sympathetic vasomotor activity.

PMID- 7815694
TI  - [Effects of hyperventilation upon the spinal pain modulating system (third
      report)].
AB  - The purpose of this study is to investigate the mechanisms of the effect of
      hyperventilation on the spinal pain modulating system by using phentolamine.
      Under enflurane anaesthesia, cats received mid-collicular decerebration and
      lumbar laminectomy. The spinal cord was transected at T12-L1. WDR cells,
      responding primarily to noxious peripheral stimuli, were sampled with a
      microelectrode at the depth of 2,000 microns from the cord dorsum. Following the
      control period, ventilation was changed to induce hypocapnia of PCO2 20-25 mmHg.
      After activities were well suppressed, phentolamine 0.5 mg with normal saline 1.0
      ml was injected on the spinal cord. Changes of firings were investigated. When
      normocapnia was resumed, recovery followed. Hypocapnia of PCO2 20-25 mmHg
      significantly suppressed the activities of WDR cells. Phentolamine significantly
      antagonized the suppressive effects of hyperventilation upon the activities of
      WDR cells. Our results suggest that the hyperventilation has suppressive effects
      on single-unit activity of WDR cell and the mechanisms of those suppressive
      effects are related to adrenergic pain modulating system.

PMID- 7815695
TI  - [Anatomical consideration of anesthetic dispersion into abdominal cavity causing
      broad unilateral anesthesia after inadvertent local anesthetic infusion into
      endothoracic fascia].
AB  - Recently we reported a case of inadvertent migration of an epidural catheter into
      the endothoracic fascia. Anesthetic injection into the fascia brought a broad
      unilateral analgesia. To clarify the mechanism of anesthesia. We studied how the
      anesthetic agent spreads into the abdominal cavity from the endothoracic fascia.
      The crimson dye, the substitute of the anesthetic agent, reached the transversial
      fascia in the abdominal cavity through medial and lateral arcuate ligament.
      Subcostal nerve, iliohypogastric nerve, ilioinguinal nerve, genitofemoral nerve
      and lateral femoral cutaneous nerve were found to be in the course of dye
      dispersion. The renal adiposal fascia plays a role of a reservoir for the
      anesthetic agent and prevents the further anesthetic dispersion.

PMID- 7815696
TI  - [Effect of deliberate hypotension on renal functions during epidural block plus
      inhalation anesthesia: a comparison of prostaglandin E1 and trimethaphan].
AB  - To clarify the effect of prostaglandin E1 (PGE1) or trimethaphan (TMP) on the
      kidney during deliberate hypotension induced with epidural block plus inhalation
      anesthesia, we compared renal functions and renal tubular injury between the
      patient with PGE1-induced hypotension (n = 22) and those with TMP-induced
      hypotension (n = 18) undergoing spherical acetabular osteotomy. Hypotension was
      maintained at 75-80 mmHg of the systolic radial artery pressure for two hours.
      The urine volume, creatinine clearance, fractional sodium excretion and free
      water clearance were maintained within normal limits and they were not different
      between the two groups. The mean NAG index increased significantly to normal
      upper limits during hypotension in the PGE1 group but did not increase in the TMP
      group. However, there was no difference in the NAG index between the two groups.
      The changes in serum ADH level were not different between the two groups
      perioperatively. These results suggest that renal functions are not influenced by
      controlled hypotension induced with PGE1 or TMP during epidural plus general
      anesthesia.

PMID- 7815697
TI  - [The effects of continuous interpleural vs. epidural infusion for postoperative
      pain relief following thoracotomy].
AB  - We studied whether continuous interpleural infusion of bupivacaine would be
      effective in alleviating pain after thoracotomy compared with effect of
      continuous epidural infusion of bupivacaine and buprenorphine. Twenty patients
      who had received thoracotomy and lobectomy were randomly divided into two groups
      to receive continuous interpleural infusion (IP group) of 0.5% bupivacaine at the
      rate of 5 ml.h-1 or continuous epidural infusion (E group) of 0.25% bupivacaine
      and 0.025 buprenorphine at the rate of 1 ml.h-1. The patients assessed their
      level of pain using a 100 mm visual analog scale (VAS) at rest and on coughing or
      changing the posture, verbal descriptor pain scale (VDPS), and times of
      supplemental analgesic. Assessment was performed at 7 points (mornings and
      evenings) for 3 postoperative days. In the evening of the day of surgery, VAS at
      rest in IP group was significantly higher than one in E group, but VASs at rest
      were similar in both groups from the first postoperative day to the third
      postoperative day. VAS on coughing or changing the posture in IP group was
      significantly higher than in E group in the evening of the day of surgery, and
      VASs on coughing or changing the posture in IP group were higher than in E group
      for 3 postoperative days. Supplemental analgesics were administered significantly
      more often than in E group in the evening of the first postoperative day. We
      conclude that continuous interpleural infusion does not give better analgesia
      than continuous epidural infusion after thoracotomy.

PMID- 7815698
TI  - [Effect of intraoperative stored blood transfusion on plasma neutrophil elastase
      and its modification by ulinastatin].
AB  - The effect of intraoperative stored blood transfusion on the changes in plasma
      neutrophil elastase (PMN-E) was studied in packed red cell, and in the patients
      transfused with stored blood (400-1000 ml) during surgery (n = 22), compared with
      the control in patients who had not received transfusion (n = 6). PMN-E was
      measured as elastase.alpha 1-antitrypsin complex (EAC) and the effect of
      ulinastatin (UTI) treatment on EAC was also evaluated. There was a significant
      correlation between transfusion volume and EAC or EAC/WBC (r2 = 0.65, P < 0.05
      and r2 = 0.51, P < 0.05; respectively). There was no significant correlation
      between transfusion volume and EAC (r2 = 0.44, P > 0.05) in patients with UTI
      treatment during blood transfusion. These results and increased H2O2
      concentration of expired breath in the patient whose plasma EAC exceeded 1,000
      micrograms.l-1, suggested PMN-E is released from triggered neutrophil by
      increased EAC.

PMID- 7815699
TI  - [Effects of hyperoxic exposure on hemopoiesis].
AB  - Effects of oxygen inhalation on hemopoiesis were investigated in mice and
      following results were obtained. 1) The numbers of pluripotent hemopoietic stem
      cells (CFU-S) and granulocyte-macrophage progenitor cells (GM-CFC) in murine bone
      marrow and spleen decreased significantly from day 1 of exposure to 70% and 100%
      oxygen. 2) The numbers of CFU-S and GM-CFC did not recover in mice that were
      exposed to 100% oxygen for 1 and 2 days followed by air exposure for 7 days.
      These results suggest that inhalation of more than 70% oxygen for 1 day induces
      inhibitory effects of the hemopoietic stem cells, and 100% oxygen exposure over 1
      day can cause irreversible damage to the hemopoiesis.

PMID- 7815700
TI  - [Psychological evaluation of patients by state-trait anxiety inventory in pain
      clinic].
AB  - In 84 outpatients who visited our pain clinic, we evaluated their anxiety before
      the first examination, using State-Trait Anxiety Inventory. State anxiety scores
      were high in all the patients regardless of their underlying disease. Trait
      anxiety scores in patients with chronic pain such as postherpetic neuralgia or
      cervic-shoulder-hand syndrome were higher than in patients with facial nerve
      palsy, sudden hearing loss or herpetic pain. This study indicates that
      psychosomatic management is mandatory for patients with chronic pain.

PMID- 7815701
TI  - [Influence of age on cardiac pump function during laparoscopic cholecystectomy-
      measurements by ear densitography].
AB  - Using ear densitography, consisting of photoelectric plethysomography and Holter
      electrocardiography, we measured systolic time intervals (STI) in 21 patients,
      ASA class 1 and 2, undergoing laparoscopic cholecystectomy using CO2 insufflation
      under general anesthesia (neuroleptanesthesia with isoflurane in air, FIO2 0.5).
      The patients were divided into two groups: Y-group (10 patients under 59 years of
      age) and O-group (11 patients over 60 years of age). We investigated the
      influence of age on cardiac pump function during pneumoperitoneum non-invasively.
      Y-group showed improvement of cardiac pump function (reduction of PEP/LVET) from
      30 minutes after the beginning of insufflation and quick recovery of cardiac
      function immediately after deflation. O-group showed a tendency of increasing
      PaCO2 and arterial diastolic pressure, and delayed recovery of cardiac function
      (elongation of PEP at 60 minutes, and increase of PEP/LVET at 60 and 90 minutes,
      respectively, after insufflation). Hypertension and tachycardia were apparent
      immediately after pneumoperitoneum in the O-group. We conclude that special care
      and monitoring are mandatory for the aged patients with impaired cardiac or
      respiratory function during laparoscopic surgery.

PMID- 7815702
TI  - [Effect of sevoflurane on blood flow velocity in the vertebral artery].
AB  - Blood flow velocity in the vertebral artery was measured using transcranial
      Doppler sonography during sevoflurane anesthesia in 12 patients in the knee-chest
      position. The correlation between mean arterial blood pressure (MBP) and mean
      blood flow velocity in the vertebral artery (Vmean) was significant in each
      patient. Normalized data expressed as a percentage of the individual arithmetic
      means permitted a composite analysis of data from all patients. Linear regression
      of normalized MBP (%MBP) on normalized Vmean (%Vmean) showed %Vmean = 24.8 +/-
      0.75 %MBP (r = 0.78, P < 0.01). The results of the present study suggest that
      fluctuations in systemic blood pressure may lead to fluctuations in cerebral
      blood flow. Therefore, the use of sevoflurane anesthesia must be accompanied by
      careful management of blood pressure during surgery.

PMID- 7815703
TI  - [Evaluation of midazolam premedication for preoperative anxiolysis].
AB  - To evaluate the anxiolysis property of midazolam, 60 patients undergoing minor
      gynecological surgery were given midazolam 0 mg (n = 20), 2.5 mg (n = 20) or 4 mg
      (n = 20) intramuscularly as premedication 1 h before their entrance to operating
      theater. The degree of anxiety was evaluated objectively using the State-Trait
      Anxiety Inventory (STAI). STAI test was performed twice: on the day before
      operation and 1 h after receiving preanesthetic premedication. In only midazolam
      4 mg group, anxiety was reduced significantly in the operating room compared to
      the day before operation. It is concluded that midazolam (4 mg) is suitable to
      reduce the preoperative anxiety in patients who are to undergo minor
      gynecological surgery.

PMID- 7815704
TI  - [Changes in anal canal pressure during caudal and lumbar epidural anesthesia].
AB  - To compare anesthetic effect of caudal and lumbar epidural anesthesia, anal canal
      pressure during these anesthesia was measured. Anal canal pressure under resting
      condition decreased soon after injection of local anesthetics into epidural space
      in both groups. In early post injection stage the pressure decreased more in
      caudal group than in lumbar epidural group. The pressure when anus was contracted
      at will fall significantly further in caudal group than in lumbar group. These
      results suggest that caudal anesthesia should be utilized for obtaining full
      muscle relaxation of anal area in a short time compared with lumbar epidural
      anesthesia.

PMID- 7815705
TI  - [Hormonal changes during removal of aldosterone-producing adrenal tumor under
      sevoflurane anesthesia].
AB  - We measured plasma aldosterone, cortisol, ACTH and catecholamine concentrations
      during removal of aldosterone-producing adrenal tumor under sevoflurane
      anesthesia in four adult patients. Sevoflurane anesthesia alone did not affect
      the plasma levels of aldosterone, cortisol, ACTH and catecholamine. Plasma
      aldosterone levels increased significantly with surgical stimulation and reached
      the peak value before surgical manipulation. Thereafter they declined in
      magnitude and reached the value below the peanesthetic levels at recovery from
      anesthesia. Plasma cortisol and ACTH levels increased significantly with surgical
      stimulation, and plasma ACTH levels reached the peak values after the emergence
      from anesthesia in the recovery room. Plasma catecholamine levels increased with
      surgical stimulation, but the increase in plasma epinephrine levels was more
      striking than that in plasma norepinephrine levels during surgical manipulation
      of the tumor. Hypertension during manipulation of the tumor was demonstrated to
      correlate with increase in plasma epinephrine levels but not with plasma
      aldosterone levels. Sevoflurane gave us no trouble during anesthetic management
      for removal of aldosterone-producing adrenal tumor. We conclude that sevoflurane
      anesthesia is a better choice for surgery for primary aldosteronism.

PMID- 7815706
TI  - [Effects of in vivo pretreatment with various barbiturates on lidocaine
      metabolism in rat liver microsomes].
AB  - In male Wistar rats, we studied the effects of in vivo pretreatment with
      phenobarbital (PB), amobarbital (AB), hexobarbital (HB), pentobarbital (PT) or
      thiamylal (TI) on hepatic microsomal enzymes, and on deethylation of lidocaine in
      the microsomes. The rats of pretreatment groups received 0.1 ml of the above
      barbiturates (320 mumol.kg-1) and the control group received intramuscular
      injection of 0.9 % NaCl solution for 4 days. NADPH-cytochrome C reductase of the
      PB and AB groups increased significantly in activity and cytochrome b5 of only PB
      group increased in content. After the pretreatment with PB, TI produced higher
      microsomal cytochrome P-450 contents than in the control group. The potency of P
      450 induction was in descending order of PB, TI, AB, HB and PT. Also we found the
      positive linear relationship between the potency of P-450 induction and the
      elimination half time (t1/2 beta) of the barbiturates. The activities of
      lidocaine deethylase with microsomes per P-450 of the pretreated rats with these
      five barbiturates (PB, AB, HB, PT and TI) were 2.4, 1.9, 2.2, 1.5 and 2.2 times
      of control values, respectively. Based on these results, we conclude that
      lidocaine deethylase activity of P-450 is increased by these five barbiturates
      whether levels of P-450 are increased quantitatively, or not.

PMID- 7815707
TI  - [Hormonal changes and pituitary histological and immunocytochemical studies of
      patients with multiple organ failure].
AB  - OBJECTIVE: We investigated the correlation between the endogenous hormonal
      changes of pituitary-adrenal and pituitary-thyroid hormones and the prognosis of
      patients in multiple organ failure, and elucidated the mechanism of blunted
      thyrotropin (TSH) secretion by histological and immunocytochemical studies of
      anterior pituitary glands. PATIENTS: Forty-three patients were studied who had
      been admitted to the intensive care unit of Sapporo Medical University Hospital
      and had been diagnosed as having multiple organ failure. MEASUREMENTS: Pituitary
      adrenal hormones [corticotropin (ACTH), cortisol] and pituitary thyroid hormones
      [TSH, triiodothyronin (T3), free-T3, thyroxine (T4), free-T4, thyroxine-binding
      globulin (TBG)] were measured, and TSH and prolactin (PRL) responses thyrotropin
      releasing hormone (TRH) were examined within 24 hours of admission to the ICU.
      Individual variables were compared between survivors (n = 19) and nonsurvivors (n
      = 24). Thirteen patients (five survivors, eight nonsurvivors) were investigated
      again before discharge from the ICU or death. Morphology was examined by
      hematoxilin-eosin staining, and avidin-biotin-peroxidase complex immunostaining
      was used to demonstrate the spectrum of TSH in 14 nonsurvivors. RESULTS: (1) ACTH
      levels remained within the normal range, while cortisol levels increased to above
      normal levels. Neither hormone showed significant differences between survivors
      and nonsurvivors. In nonsurvivors, cortisol levels decreased before death despite
      the increased ACTH levels. (2) T3 and free-T3 levels decreased markedly to below
      normal values, and reverse-T3 levels increased markedly to above normal values.
      Nonsurvivors showed significant differences in TSH, T4 and reverse-T3 levels
      compared with survivors. (3) TSH response to TRH was blunted in both groups but
      PRL response to TRH was normal. Nonsurvivors showed severely depressed TSH
      response. Nonsurvivors continued to show blunted TSH response to TRH, while this
      improved in survivors. (4) The histological study did not show very serious
      damages to anterior pituitary glands as TSH secretion was depressed. Many TSH
      immunoreactive cells were also observed by immunocytochemical study. CONCLUSION:
      Decreased cortisol, low T4 levels and blunted TSH response to TRH correlated with
      mortality in MOF patients. Histological and immunocytological studies suggest
      that blunted TSH secretion is not caused by pituitary damages or TSH exhaustion
      but by disturbances in TSH secretion. This blunted TSH secretion is reversible
      and its improvement is an indicator of survival.

PMID- 7815708
TI  - [Changes in plasma concentrations of human hepatocyte growth factor before and
      after major intra-abdominal surgery under nitrous oxide-sevoflurane anesthesia].
AB  - The measurements of human hepatocyte growth factor (hHGF) in plasma and liver
      function tests were performed in 23 patients before and after major intra
      abdominal surgery under nitrous oxide-sevoflurane anesthesia. Plasma
      concentrations of hHGF in 12 patients with normal liver function (Group 1) and in
      11 patients with liver dysfunction (Group 2) were 0.34 +/- 0.07 and 0.44 +/- 0.12
      ng.ml-1 (mean +/- SD) before the surgery, respectively. After the surgery, plasma
      concentration of hHGF remained unchanged in Group 1, but significantly increased
      to 0.61 +/- 0.32 ng.ml-1 in Group 2. Other routine laboratory data reflecting
      hepatic functions remained unchanged in both groups. These results suggest that
      liver damage during surgery and anesthesia occurs more likely in patients with
      liver dysfunction than in patients with normal liver function, and hHGF can be a
      more sensitive indicator of hepatic damage than conventional liver function
      tests.

PMID- 7815709
TI  - [Individual differences in the sensitivity to the effect of alcohol upon pain].
AB  - In this study, the relationship between pain threshold and blood ethanol level,
      and also the effect of alcohol sensitivity upon the threshold was investigated.
      Thirty-one healthy subjects, aged 20 to 62 years, were studied. The genotypes at
      the aldehyde dehydrogenase 2 (ALDH) locus were determined in each subject to
      evaluate the alcohol sensitivity. The subjects were divided into three groups
      based on the ALDH2 genotypes, i.e., the ALDH2*1/*1 (homozygous active ALDH), the
      ALDH2*1/*2 (heterozygous inactive ALDH) and the ALDH2*2/*2 (homozygous inactive
      ALDH). The subjects were given orally 0.4 g.kg-1 and/or 0.8 g.kg-1 of ethanol.
      Venous blood samples were collected at 30, 60, 120, 180, and 240 min after
      ethanol intake and blood ethanol and acetaldehyde levels were determined. Prior
      to the ethanol intake and at each sampling of the blood, the pain thresholds were
      measured by three stimulating methods, i.e., a mechanical method (algometer), a
      thermal method (Nakahama's pain meter NYT-5) and a chemical method (potassium
      iontophoretic meter). In the ALDH2*1/*1 and ALDH2*1/*2 groups, the pain threshold
      measured by the three methods increased with the elevation of blood ethanol
      levels, especially the threshold by the mechanical method showed clear rise with
      blood ethanol level. The subjects who belonged to the ALDH2*2/*2 group showed a
      high blood acetaldehyde level and various psychophysical symptoms. The results of
      the three tests had no relationships with the variation of blood ethanol levels.

PMID- 7815710
TI  - [Clinical evaluation of controlled hypotensive anesthesia with MR7S1].
AB  - Efficacy, safety and the optimal dose of MR7S1, an injectable preparation of
      sodium nitroprusside, were studied in 37 patients (ASA class I and II) under
      nitrous oxide-oxygen-enflurane anesthesia. MR7S1 was administered by intravenous
      infusion. The dose of MR7S1 was increased gradually starting from 0.25
      micrograms.kg-1.min-1 to the dose which could achieve the target value of
      systolic blood pressure (80-100 mmHg). Thereafter this dose level was maintained.
      During the period in which the dose was increased, the blood pressure was reduced
      in proportion to the rate of administration. With the rate of administration of
      1.0 to 3.0 micrograms.kg-1.min-1, a significant decrease in systolic blood
      pressure (SBP) was observed compared with the pretreatment level of SBP. During
      the maintenance period, the SBP was maintained around 80 to 100 mmHg at a rate of
      administration of 0.25 to 3.5 micrograms.kg-1.min-1. Two out of 37 patients
      showed a slight decrease in PaO2, but these values returned to normal without any
      treatment. These findings suggest that MR7S1 is a useful agent to control blood
      pressure for the hypotensive anesthesia.

PMID- 7815711
TI  - [A comparison between neuromuscular blocking effects of pipecuronium and
      vecuronium; a double blind controlled study in collaboration with 5 departments
      of anesthesiology].
AB  - Neuromuscular blocking effects of pipecuronium bromide 0.04 mg.kg-1 were compared
      those of vecuronium bromide 0.08 mg.kg-1 in a double blind study. Fifty surgical
      patients (ASA I or II) were allocated randomly to two groups of each 25 cases and
      they were anesthetized with nitrous oxide 4 l.min-1, oxygen 2 l.min-1 and
      isoflurane 1 MAC. Neuromuscular blockade was monitored by using mechanical twitch
      responses of the thumb to electrical stimulations of the ulnar nerve. Adequate
      neuromuscular relaxation for surgery of 85.8% to 100% block was obtained by this
      dose of pipecuronium. The duration of action and recovery time from 75% to 25%
      block were longer than those produced by twice the dosage of vecuronium (62.3 +/-
      37.15 vs. 40.4 +/- 16.09 min, and 48.1 +/- 22.0 vs. 19.9 +/- 10.8 min, P < 0.05).
      The blocks by both drugs responded to neostigmine. Cardiovascular side effects of
      the both agents were not found. From these results, it is concluded that
      pipecuronium is a useful nondepolarizing relaxant with a long duration of action
      and negligible side effects.

PMID- 7815712
TI  - [An unusual supine hypotensive syndrome during cesarean section: the importance
      of trying right tilt if there is a poor response to left tilt].
AB  - A case of severe supine hypotensive syndrome in a parturient associated with
      breech presentation was presented. It is suggested that failure of left tilt to
      prevent the hypotension was associated with anatomical displacement of the uterus
      to the right. The importance of trying right tilt, if response to left tilt is
      poor, is emphasized.

PMID- 7815713
TI  - [Effects of repeated sevoflurane anesthesia on hepatic and renal function in a
      pediatric patient].
AB  - A 10-yr-old boy with an injured lower extremity received sevoflurane anesthesia 5
      times within 40 days. Laboratory tests for hepatic and renal function i.e., serum
      transaminase (glutamic oxaloacetic transaminase, glutamic pyruvic transaminase,
      gamma-glutamyl transpeptidase), serum cholinesterase, plasma protein, serum
      cholinesterase, serum bilirubine, serum lactic dehydrogenase, serum prothrombin
      time, blood urea nitrogen, serum creatinine, beta 2-microglobulin, N-acetyl-D
      glucosamidase and 24 hr-creatinine clearance remained within normal ranges
      throughout his perioperative period. Repeated sevoflurane anesthesia did not
      exert any adverse effect on hepatic and renal function in this patient.

PMID- 7815714
TI  - [Intracranial subdural hematoma following spinal anesthesia].
AB  - We report a case of intracranial subdural hematoma following spinal anesthesia in
      a 28-year-old woman. Subdural hematoma is a very rare, but life-threatening
      complication. When a patient complains of persistent post spinal headache, one
      should consider the possibility of subdural hematoma and carry out a careful
      examination, including MRI or CT scan.

PMID- 7815716
TI  - [Usefulness of continuous intra-arterial blood gas monitoring in a patient
      undergoing tracheal transection and reconstruction].
AB  - Usefulness of a new continuous intra-arterial blood gas monitoring system
      (PB3300, Puritan-Bennett, Carlsbad, California) was evaluated in a patient with
      tracheal cancer who was undergoing tracheal transection and reconstruction. The
      PB3300 detected continuous changes in pH, PaCO2, and PaO2 during the surgical
      intervention and provided reliable information to take appropriate therapeutic
      measures. PB3300 was superior to pulse oximetry because the latter can not detect
      changes in PaO2 more than 100 mmHg accompanying pulmonary dysfunction caused by
      surgical procedures. We conclude that the PB3300 is a useful monitor when used
      during anesthetic management of the patient who needs frequent arterial blood gas
      analyses.

PMID- 7815715
TI  - [Effect of indomethacin as an adjunct to postoperative pain relief by continuous
      epidural infusion of bupivacaine and buprenorphine].
AB  - We examined the analgesic effects of indomethacin as an adjunct to postoperative
      epidural analgesia in 40 patients who underwent upper abdominal surgery. Twenty
      patients in control group were epidurally given 0.1 mg of buprenorphine in 8 ml
      of 0.25% bupivacaine immediately after surgery and subsequently infused 15
      micrograms buprenorphine in 1 ml of 0.25% bupivacaine at a rate of 1 ml.h-1 for
      48 h. The remaining 20 patients were rectally given 50 mg of indomethacin in
      addition to the same epidural method described above. The patients who did not
      need additional narcotics in the control and indomethacin groups were 45% and
      80%, respectively (P < 0.05). In upper abdominal surgery, postoperative pain
      relief by epidural buprenorphine and bupivacaine plus rectal indomethacin was
      more effective than that by epidural buprenorphine and bupivacaine.

PMID- 7815717
TI  - [Strategies of general anesthesia for cleft palate surgery in Cambodia].
AB  - Hare lip and cleft palate surgery team activities in Cambodia were launched in
      1989 by a non-governmental Japanese organization, Operations Unies. The
      objectives of the project are to provide appropriate surgical treatment and safe
      general anesthesia for local patients and also to conduct technology transfer of
      general anesthesia and surgery to the local medical staffs. From June 1991 to
      January 1993, a surgery/anesthesia team was dispatched 4 times and a total of 130
      patients received surgical treatments under general anesthesia. Anesthesia
      techniques employed included total intravenous anesthesia in 70 patients (54%)
      and intravenous anesthesia with 0.3-0.7% of halothane in 60 patients (46%). There
      were no major complications, such as airway obstruction and apnea, in the
      recovery room and in the ward. The reasons why we chose intravenous agents are
      difficulty in obtaining inhaled agents in Cambodia and lack of scavenging system
      in a operating room. Although halothane anesthesia with spontaneous breathing has
      been recommended in developing countries, total intravenous anesthesia could be
      one of the applicable techniques in these countries. In Cambodia, shortage of
      medical doctors and the absence of anesthesiologist constitute a major barrier to
      technology transfer in clinical anesthesia.

PMID- 7815718
TI  - [A new index of disease activity in Crohn's disease].
AB  - A comprehensive assessment including subjective and objective parameters seems to
      be essential for evaluation of disease activity in Crohn's disease. The aim of
      the present study was to develop an activity index (AI) of Crohn's disease,
      composed of both subjective and objective variables. Data composed of a total 132
      clinical examinations in 100 patients with Crohn's disease were used to determine
      the AI. Three physicians independently evaluated disease severity in each
      patient. Stepwise multiple regression analysis was carried out with the overall
      evaluation as a dependent variable, and with 18 parameters as independent
      variables. Analysis showed that the following seven variables had a significant
      correlation with physician's overall evaluation: abdominal pain, abdominal
      tenderness, complications, C-reactive protein (CRP), body temperature, diarrhea,
      and body mass index (BMI). AI was expressed as follows: AI = 3.5 x abdominal pain
      + 3 x abdominal tenderness + 3 x complications + CRP + 3 x body temperature + 4 x
      diarrhea - 0.4 x BMI. AI values below 15 corresponded to inactive disease, values
      between 15 and 25 to mild disease, values between 25 and 35 to moderate disease,
      and values above 35 to severe disease. This study suggests that the activity
      index is useful for evaluation of the effect of medical treatment in Crohn's
      disease.

PMID- 7815719
TI  - [Macroscopic classification and kinetic alternations in the superficial lesion of
      colorectal neoplasms].
AB  - To clarify relation between macroscopic appearance and the mode of tumor growth
      in the superficial lesion of colorectal neoplasms, we compared their colonoscopic
      findings with histological architecture of tumor cells. Macroscopic type was
      classified into the superficial elevated lesion (II a, n = 42, mean 5.14mm) and
      the superficial depressed lesion (n = 42, mean 3.84mm). The latter was further
      divided into 3 subtypes; subtype A, an irregular depression with high marginal
      elevation (Dep (A), n = 20); subtype B, an irregular depression with irregular
      marginal elevation (Dep (B), n = 7); subtype C, a clear and wide depression
      without marginal elevation (Dep (C), n = 15). Histological architecture was
      evaluated by the transmucosal growth index (TGI) of tumor cells, which is a ratio
      of tumor width contacting with the muscularis mucosae against that of tumor
      surface, and by the distribution of proliferating cells detected by Ki-67
      antibody (MIB-1). In adenomas TGI increased with a degree of central depression
      (IIa < Dep(A) < Dep(C)). In carcinomas TGI was high irrespective of their
      macroscopic forms. Ki-67 labeling indices tended to increase with histological
      atypia. Adenomas with severe atypia showed a high labeling consistent with
      carcinomas. In both adenomas and carcinomas, Ki-67 positive cells were mainly
      noted in upper third of neoplastic glands in II a, Dep (A) and Dep (B) neoplasms.
      By contrast, Dep (C) neoplasms lost a preferential distribution of proliferating
      cells, which reached the whole neoplastic glands. These results suggest that Dep
      (C) adenomas and carcinomas have a unique histopathological architecture in terms
      of a high TGI and an enlarged distribution of proliferating cells, implying a
      high malignant potential.

PMID- 7815720
TI  - [Deterioration of liver function following endoscopic injection sclerotherapy of
      esophageal varices--significance of a new index for liver function "delta TB"].
AB  - Changes of liver functions associated with endoscopic injection sclerotherapy
      (EIS) in which less than 6 ml of 5% ethanolamin oleate was used were investigated
      in 50 patients with remarkable esophageal varices. The index used for evaluating
      hepatic reserve was the difference of total bilirubin in serum between
      immediately and 15 hours after EIS and was tentatively named as "delta TB"
      (normal range < or = 0.1). In the patients classified as Child-Pugh A (n = 25),
      Child-Pugh B (n = 19) and Child-Pugh C (n = 6), delta TB was 0.04 +/- 0.30, 0.23
      +/- 0.41, and 0.54 +/- 0.21, respectively. One month after the entire sessions of
      EIS, the changes of liver function tests before and after EIS were compared in 45
      cases. It was disclosed that delta TB was elevated in parallel with the severity
      of their liver dysfunction before EIS. Also, delta TB seems to reflect the
      prognosis of the patients treated by EIS for some extent, since the survival
      period of the cases treated by EIS were correlative with delta TB (r = -0.734, p
      < 0.01), and delta TB of 20 cases who survived for longer than 5 years after EIS
      was 0.04 +/- 0.32. Therefore, delta TB seems to be a useful marker for estimating
      the influence of EIS on liver function.

PMID- 7815721
TI  - [An angiographic study on the pathological features of multiple hepatocellular
      carcinoma].
AB  - Seventy-one patients with untreated hepatocellular carcinoma (111 tumors) were
      studied angiographically to investigate the pathological features of multiple
      carcinoma. The 111 tumors comprised 23 lesions resected from 14 patients and 88
      lesions measuring 3 cm or less in diameter detected in 57 patients who did not
      undergo resection. Hemodynamically, major lesions exhibited an increase in
      frequency of tumor angiogenesis and intensity of tumor stain with an increase in
      diameter. Analysis of angiographic features of tumors measuring 2 cm or less in
      diameter revealed a greater vascularity in intrahepatic metastatic foci than in
      primary foci, demonstrating a difference between them. When multiple tumors were
      classified into the isolated, concentric or disseminated type in terms of the
      pattern of their distribution, their angiographic findings suggested that min or
      lesions of the concentric or disseminated type might represent local metastases
      spread from the primary focus, and that those of the isolated type might
      represent multicentric occurrence in the liver.

PMID- 7815722
TI  - [Diagnosis of gallbladder cancer by imaging techniques: problems, limitations and
      their explanations, especially with ss invasive cancer].
AB  - The preoperative diagnosis of less than ss depth gallbladder cancer is difficult.
      Its preoperative diagnosis rate was low (27.5%), and even lower with the presence
      of concomitant gallstone. In the latter case, the diagnosis rate was particularly
      low when the stones diameter was greater than 1 cm. Gallstones are frequently
      associated with macromorphologically invasive type of gallbladder cancer and this
      may be the reason for the lower diagnostic rate. We compared preoperative
      diagnosis rate of ultrasonography (US), computed tomography (CT) and drip
      infusion cholecystography (DIC) for each invasion depth. In US, the preoperative
      diagnosis rate for m depth invasion was 6/16 (37.5%), pm depth was 1/13 (7.7%),
      and ss depth was 14/41 (34.1%). In CT, its rate for m depth was 3/11 (27.3%), pm
      depth was 1/10 (10.0%), and ss depth was 11/37 (29.7%). In DIC, its rate for m
      depth was 3/11 (27.3%), pm depth was 1/10 (10.0%), and ss was depth 1/23 (4.3%).
      None of the currently used imaging techniques were very accurate in diagnosing
      gallbladder cancer. Thus, during preoperative work up, if one discovers a
      gallbladder full of stones, stones of greater than 1 cm in diameter, thickened
      gallbladder wall, or a non visualized gallbladder with DIC, gallbladder cancer
      must be highly suspected.

PMID- 7815723
TI  - [Diagnostic strategy for malignancy and parenchymal invasion of so-called mucin
      producing tumor of the pancreas].
AB  - This study investigated diagnostic indications of malignancy and parenchymal
      invasion of so-called mucin-producing tumor of the pancreas (MPT). We reviewed 40
      patients with this type tumor. In diagnosis of malignancy, jaundice, mural nodule
      (EUS), displacement or compression of the portal vein (angiography), compression
      of the common bile duct (cholangiography) and Group IV-V in biopsy, Class III-V
      in brushing cytology were important. In diagnosis of parenchymal invasion, solid
      mass (US, EUS, CT), arterial encasement (angiography), defect in the common bile
      duct (cholangiography), stenosis or obstruction of the MPD (pancreatography) and
      elevation of serum CA19-9, CEA levels were important. By these findings, MPT
      diagnosed as benign can be observed without surgical treatment. On the other
      hand, MPT diagnosed as malignant must be treated by surgical resection, and
      operative procedure must be chosen according to whether the MPT was accompanied
      by parenchymal invasion or not.

PMID- 7815724
TI  - [Evaluation of Helical scanning CT in the diagnosis of pancreatic diseases].
AB  - We discuss the usefulness of Helical scanning CT (Helical CT) in the 52 patients
      with space occupying lesions of the pancreas. Information acquired during the
      early phase was found to be particularly useful in the evaluation of the extent
      of pancreatic carcinoma. The diagnostic rate of pancreatic tumors by Helical CT
      was 78% in 18 operative cases. The detection rate of involvement of the major
      arteries around the pancreas was compared with angiographic results in 22 cases
      each other, and the overall accuracy of Helical CT was 100%. On the other hand,
      the detection rate of PV invasion by Helical CT was compared with histological
      results in 14 cases, and the overall accuracy was 71.4%. In the cine mode and the
      multiplanar reconstruction (MPR) image, the courses of the major blood vessels
      and the degree of invasion into the blood vessels by pancreatic carcinoma could
      be continuously observed, both enabled reconstruction of the lesion and
      surrounding areas three dimensionally.

PMID- 7815725
TI  - [A case of multiple gastric hyperplastic polyps: onset during omeprazole therapy
      in scleroderma patient].

PMID- 7815726
TI  - [A case of multiple gastric carcinoids in type A gastritis].

PMID- 7815727
TI  - [A case of superior mesenteric artery thrombosis detected by enhanced CT].

PMID- 7815728
TI  - [A case of multiple thrombus of superior mesenteric vein and portal vein with
      ischemic colitis].

PMID- 7815729
TI  - [A case of jejunal leiomyoma in the unknown site of bleeding findings by
      scintigraphy with 99mTc red blood cells].

PMID- 7815730
TI  - [A case of Munchausen syndrome with frequent anal bleeding and severe iron
      deficiency anemia].

PMID- 7815731
TI  - [Hepatocellular carcinoma complicating primary biliary cirrhosis--a case report
      and a review of the literature].

PMID- 7815732
TI  - [Metastasis of hepatocellular carcinoma to the small intestine and the
      retroperitoneum].

PMID- 7815733
TI  - [A case of portohepatic vein fistula successfully treated with balloon
      embolization for the portal-systemic encephalopathy and metabolic abnormality of
      glucose and amino acids].

PMID- 7815734
TI  - [A case of primary sclerosing cholangitis that was distinguishable from bile duct
      carcinoma by PTCS].

PMID- 7815735
TI  - [Endoscopic ultrasonography (EUS) through a soft balloon].

PMID- 7815736
TI  - [Use of the PCR in the quantitation of Mn-SOD and TNF-alpha mRNA expression by
      gastric mucosa in gastric cancer].

PMID- 7815737
TI  - [Diagnosis on wall invasion of the gallbladder cancer--effectiveness of an
      operative ultrasonography examination pouring solution into the subserosa].

PMID- 7815738
TI  - [New classification of hypertension based on renal mechanisms].
AB  - The renal mechanisms of hypertension were reviewed, and new way to classify
      hypertension based on renal mechanisms was proposed. Theoretically, the
      pressurenatriuresis relationship can be affected in two different ways; either a
      parallel shift along the blood pressure axis toward a higher blood pressure level
      or a depression in the slope. The parallel shift of the pressure-natriuresis
      relationship induces non-sodium sensitive hypertension, while the depressed slope
      induces sodium sensitive hypertension. Since the degree of the shift of the
      pressure-natriuresis relationship is determined by the preglomerular vascular
      resistance from heart to glomeruli, non-sodium sensitive hypertension should be
      based on the increased preglomerular vascular resistance. On the other hand, the
      slope of the pressure-natriuresis relationship is determined by glomerulo-tubular
      balance of sodium, which is mainly controlled by the difference between the whole
      kidney ultrafiltration coefficient and the rate of tubule sodium reabsorption.
      Therefore, sodium sensitivity of blood pressure is based on a decrease in the
      whole kidney ultrafiltration coefficient (due to a decrease in either filtration
      surface area per glomerulus, hydraulic permeability of glomerular filtration
      barrier or the number of glomeruli) and/or an increase in tubule sodium
      reabsorption. In sodium sensitive states, whether whole kidney ultrafiltration
      coefficient is reduced or tubule sodium reabsorption is enhanced, the glomerular
      capillary hydraulic pressure rises to compensate for the impairments in sodium
      excretory capability. If there is a linkage between sodium sensitivity of blood
      pressure and glomerular hypertension as proposed, renal failure may be expected
      to be more common in sodium sensitive types of hypertension than in non-sodium
      sensitive types.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7815739
TI  - [Induction and prevention of kidney injury induced by GSH depletion and vitamin E
      deficiency in rats].
AB  - Four-week-old Wistar male rats were fed a vitamin E (VE)-deficient diet for 8
      weeks, followed by intraperitoneal injection of DL-buthionine- [S, R] 
      sulfoximine (BSO), an inhibitor of gamma-glutamylcysteine synthetase, at the dose
      of 1 mmol/kg body weight. As we reported previously, GSH depletion by
      administration of BSO induced acute tubular necrosis in the kidney of VE
      deficient rats and was accompanied by decrease of renal TBA value and marked
      increase of renal lipofuscin content. In this study, we examined the effect of
      administration of AsA or Trolox C on these kidney injuries. AsA or Trolox C
      treatment increased renal GSH content and inhibited the increase of renal
      lipofuscin production. The increase of BUN and creatinine levels and LDH activity
      in the sera of rats administered BSO were inhibited by AsA or Trolox C treatment.
      AsA treatment completely protected the necrosis of epithelia of proximal renal
      tubules. These results suggest that GSH has an important role in preventing
      lipofuscin production through the reaction of lipid peroxides with amino acids.
      AsA spares GSH indicating that these compounds have similar antioxidant actions
      and that AsA can serve as an essential antioxidant in the presence of severe GSH
      deficiency.

PMID- 7815740
TI  - [Association of cell cycle and protein kinase C with the expression of
      cytoskeletal protein in cultured rat mesangial cells].
AB  - We conducted a study to investigate whether expression of the contractile
      proteins in cultured rat mesangial cells (MC) was associated with the cell cycle
      and protein kinase C (PKC). When growth-arrested MC were stimulated with 100 nM
      phorbol myristate acetate (PMA) for 24 hours, an increased expression of smooth
      muscle alpha-actin and vimentin was detected by immunocytochemistry. A proportion
      of the S- and G2/M-phase in MC was increased in accordance with the enhanced
      expression of contractile proteins on flow cytometry. Immunoblot analysis
      revealed that 100 nM PMA stimulated expression of alpha-actin and vimentin as a
      single band. These results indicate that expression of contractile proteins, such
      as alpha-actin and vimentin, is dependent on the cell cycle and PKC, suggesting a
      phenotypic change in which MC assume smooth muscle cell characteristics.

PMID- 7815741
TI  - [The effect of temocapril, an angiotensin-converting enzyme inhibitor with
      preferential biliary excretion, on experimental diabetic nephropathy].
AB  - Tempocapril is a novel angiotensin-converting enzyme (ACE) inhibitor which is
      preferentially eliminated via the biliary tract. To examine whether it has a
      protective effect in diabetic nephropathy like conventional ACE inhibitors which
      are eliminated via the kidney, a study was performed in streptozotocin-induced
      diabetic rats for 8 months. Male Wistar rats were divided into 4 groups (control
      rats, diabetic rats treated with temocapril at the doses of 5 mg/l or 15 mg/l of
      drinking water, and untreated diabetic rats). There was no significant difference
      in the blood glucose levels of the 3 diabetic groups. Administration of
      temocapril at both doses of 5 mg/l and 15 mg/l significantly reduced the blood
      pressure as well as the urinary excretion of albumin and N-acetyl-beta-D
      glucosaminidase. However, significant suppression of glomerular basement membrane
      hypertrophy was only induced by treatment with temocapril at the dose of 15 mg/l.
      Elevated glomerular filtration rate and filtration fraction in diabetic rats were
      decreased by tempocapril at the dose of 15 mg/l, but not significantly. These
      results indicate that tempocapril has a protective effect on diabetic nephropathy
      like conventional ACE inhibitors.

PMID- 7815742
TI  - [Measurement of antibodies to double-stranded and single-stranded DNA using
      bacteriophage lambda DNA as the antigen--avidity of antibodies to DNA in patients
      with lupus nephritis].
AB  - IgG-class antibodies to double-stranded (ds) and single-stranded (ss) DNA in
      patients with collagen disease were measured by enzyme-linked immunosorbent assay
      (ELISA) using bacteriophage lambda DNA as the antigen. Moreover, avidity of IgG
      class antibodies to both dsDNA and ssDNA in patients with systemic lupus
      erythematosus (SLE) was evaluated by ELISA as salt-dependent binding activities.
      The results are as follows: 1) Elevated IgG-class antibodies to dsDNA were
      largely restricted to patients with active SLE. Furthermore, the levels of IgG
      class antibodies to dsDNA correlated with the disease activity of SLE. 2) Lupus
      nephritis (LN) patients with nephrotic syndrome (NS) or diffuse proliferative LN
      as determined by renal biopsy had high levels of IgG-class antibodies to both
      dsDNA and ssDNA. 3) LN patients with NS showed the highest means of avidity index
      of IgG-class antibodies to both dsDNA and ssDNA. These findings suggest that the
      present method of measuring IgG-class antibodies to dsDNA is useful for the
      diagnosis and management of patients with active SLE and that IgG-class
      antibodies to both dsDNA and ssDNA with high avidity may be an important factor
      in the pathogenesis of LN with NS.

PMID- 7815743
TI  - [Study on platelet-derived growth factor (PDGF) and PDGF receptor expression in
      glomeruli and corticosteroid therapy in IgA nephropathy].
AB  - This study was designed to investigate whether expression of platelet-derived
      growth factor (PDGF) and its receptor in the glomeruli is correlated with
      clinicopathological parameters in 42 patients with primary IgA nephropathy.
      Immunohistochemical studies were conducted using frozen sections from biopsy
      specimens. The intensity of PDGF beta receptor expression in the glomeruli was
      correlated with the mesangial cell count, but not with clinical parameters, such
      as daily excretion of urinary protein and creatinine clearance. Moreover,
      overexpression of PDGF beta receptor in the glomeruli was observed in the
      patients who were responsive to corticosteroid therapy. These data suggest that
      PDGF beta receptor expression in the glomeruli of IgA nephropathy could be a
      useful marker for predicting the prognosis and effectiveness of corticosteroid
      therapy.

PMID- 7815744
TI  - [A study on glomerular hypertrophy in various renal disease].
AB  - We studied the contributions of glomerular hypertrophy in renal disease. The
      patients were 20 cases of IgA nephropathy with prolonged proteinuria, 13 cases of
      Alport syndrome and 12 cases of focal glomerular sclerosis (FGS). All patients
      had a normal creatinine level on renal biopsy. We determined the mean glomerular
      tuft area in the equatorial region of five glomeruli that showed no sclerotic
      change in each patient using an image analyzer and compared the value with the
      mean value in normal controls. Glomerular hypertrophy was defined as a value over
      the mean glomerular tuft area +1SD of normal controls. Glomerular hypertrophy was
      found in 14 IgA nephropathy cases (70.0%), 4 Alport syndrome cases (30.7%) and 8
      FGS cases (66.7%). The incidence of glomerular hypertrophy was significantly
      higher in IgA nephropathy than in Alport syndrome and FGS showed a higher
      tendency compared with Alport syndrome. Of the patients with renal insufficiency,
      4 of 6 IgA nephropathy cases (66.6%), 0 of 5 Alport syndrome cases (0%) and 1 of
      3 FGS cases (33.3%) showed glomerular hypertrophy, IgA nephropathy patients
      showed the highest incidence of glomerular hypertrophy. The interval between the
      final biopsy and renal insufficiency showed no significant difference in this
      study. In IgA nephropathy, obsolescent glomeruli were significantly increased in
      the group in which the glomerular tuft area was over the mean +2SD compared with
      the group with an area less than the mean +2SD. FGS cases showed no relationship
      between the ratio of obsolescent glomeruli to whole glomeruli and glomerular
      hypertrophy. This study suggested that glomerular hypertrophy may cause declining
      renal function in IgA nephropathy, but not in Alport syndrome.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7815745
TI  - [Serum IgA-fibronectin complex in children with various renal diseases].
AB  - IgA-Fibronectin complex (IgA-FN) has been found in the circulation of patients
      with IgA nephropathy (IgAN). It has been suggested that circulating IgA-FN is
      related to IgA deposits in the mesangial area following mesangial matrix
      expansion in IgAN. We investigated serum IgA-FN in patients with various renal
      diseases, and examined the relationship between IgA-FN and the clinico
      pathological findings. Serum IgA-FN level was measured by enzyme-linked
      immunosorbent assay (ELISA) in 35 patients with IgAN, 20 patients with Henoch
      Schonlein purpura nephritis (HSPN), and other various renal diseases in children.
      IgA-FN in patients with IgAN was significantly higher than in healthy subjects
      and patients with minimal change nephrotic syndrome. However some patients with
      membranoproliferative glomerulonephritis and lupus nephritis had a high level of
      IgA-FN. The increase in IgA-FN was correlated with macroscopic hematuria and the
      degree of proteinuria and mesangial matrix expansion in IgAN. Thus, we concluded
      that the level of IgA-FN is associated with mesangial matrix expansion.

PMID- 7815747
TI  - [Studies on the pathogenesis and pathophysiology of renal osteodystrophy. II.
      Bone histology of chronic renal failure patients at the time of starting
      hemodialysis].
AB  - We studied the relationship between the histomorphometric parameters of bone
      structure in biopsied iliac crest bone specimens and the serum biochemical
      parameters in 62 chronic renal failure (CRF) patients at the time of starting
      hemodialysis. These patients were classified into 4 groups according to Coburn's
      definition: 4 patients with osteomalacia, 1 with osteitis fibrosa, and 57 with
      mild type. Serum corrected Ca levels were significantly lower in cases with
      osteomalacia than those of mild type, which suggested that hypocalcemia was
      related to Calcification disturbance in end-stage renal failure. The bone
      histomorphometry revealed that in CRF patients, osteoid and bone resorption
      parameters were significantly higher and calcification parameters were
      significantly lower than those of normal controls. Osteoclast and osteoblast
      surfaces were significantly correlated with osteoid and bone formation
      parameters. In diabetic nephropathy patients, serum C-PTH levels were
      significantly lower than those of patients with non-diabetic nephropathies. Bone
      mass, osteoid and bone formation parameters were also significantly lower in
      diabetic nephropathy patients, which showed that low turnover bone mass decrement
      has already appeared at the time of starting hemodialysis. There was a
      significant negative correlation between serum corrected Ca levels and osteoid
      parameters. A significant relationship was also found between serum alkaline
      phosphatase levels and both osteoid and bone formation parameters. Serum C-PTH
      levels were significantly related to osteoid, bone resorption and bone formation
      parameters, demonstrating the presence of high turnover bone in secondary
      hyperparathyroidism. This study clarifies that morphological changes of bone
      structure are present at the time of starting hemodialysis in CRF patients.

PMID- 7815746
TI  - [Studies on urinary protein components in renal disease in children, II-
      Comparison between children with orthostatic albuminuria and children with
      remission of glomerulonephritis].
AB  - The urinary protein components of 14 children with orthostatic albuminuria (group
      OA) and also that of 9 children with remission of IgA nephropathy or Henoch
      Schonlein purpura nephritis (group GN) after forced lordosis were analyzed. The
      results were as follows; (1) Urinary total protein excretions after forced
      lordosis were greater than 30mg/dl in 50% of 26 children with remission of
      glomerulonephritis, therefore a high percentage of children with remission of
      glomerulonephritis were complicated with orthostatic albuminuria. (2) Urinary
      total protein excretions after forced lordosis were 150 +/- 91mg/dl in the group
      of OA and 149 +/- 88mg/dl in GN (p > 0.05). (3) In the urinary protein
      components, the percentage of urinary albumin and alpha 1-antichymotrypsin
      excretions were significantly higher in the OA group than the GN group (p < 0.01,
      p < 0.001 respectively), while the percentage of urinary transferrin, IgA and IgG
      excretions were significantly higher in the GN group than the OA group (p < 0.01,
      p < 0.001 and p < 0.05 respectively). (4) The ratio of urinary IgG/IgA and serum
      IgG/IgA was significantly lower in the GN group than the OA group (p < 0.05),
      suggesting that serum IgA tended to be excreted in urine in the GN group.

PMID- 7815748
TI  - [Numerical and functional alterations in T and B lymphocyte subpopulations in
      CAPD patients treated with recombinant human erythropoietin].
AB  - Recombinant human erythropoietin (r-HuEPO) is recognized to be effective in the
      treatment of anemia in patients on chronic dialysis. However, studies on the
      influence of r-HuEPO on the immune system are currently limited and inconsistent.
      In order to clarify the alteration of T and B lymphocyte subpopulations in
      patients on CAPD following administration of r-HuEPO, the changes in the
      expression of HLA-DR, IL2R and CD4/CD8 ratio in the peripheral blood of CAPD
      patients were evaluated using flow cytometry. In addition, the production of
      immunoglobulins in peripheral lymphocytes by enzyme immunoassays in 30 CAPD
      outpatients with anemia, who were treated with r-HuEPO in Tokai University
      Hospital, was also studied. The dose of r-HuEPO was 6,000 IU in 13 patients in
      group I and 9,000 IU in 17 patients in group II. The r-HuEPO was given
      subcutaneously once a week for up to 9 weeks. The level of hematocrit increase
      significantly following treatment with r-HuEPO. The numbers of lymphocytes and
      their CD4/CD8 ratios in peripheral blood showed no significant changes after
      administration of r-HuEPO. The count of HLA-DR-positive T lymphocytes increased
      significantly and the count of IL2R-positive T lymphocytes decreased and
      normalized after administration of r-HuEPO. In comparison with healthy controls,
      basal formation of IgG, IgA and IgM was decreased significantly in PBMC from
      patients on CAPD. Following treatment with r-HuEPO, the production of IgG, IgA
      and IgM in PBMC from CAPD patients did not show any significant changes. In
      conclusion, this study suggested that the administration of r-HuEPO altered T
      lymphocyte function and also corrected anemia in CAPD patients.

PMID- 7815749
TI  - [A case of acute renal failure in neuroleptic malignant syndrome associated with
      rhabdomyolysis--possible contributing role of hyperreninemia].
AB  - A schizophrenic woman, aged 45, was admitted complaining of high fever, oliguria,
      blackish urine, muscle swelling and pain. She had been treated for the past 3
      years with haloperidol (8 mg), levomepromazine (150 mg), chlorpromazine (75 mg),
      lithium carbonate (600 mg), bromocriptine mesilate (7.5 mg), etizolam (1 mg), and
      flunitrazepam (2 mg), Physical examination revealed her to be an obese and
      uncommunicatable woman with swelling and weakness of the extremities and
      abdominal distension without borborygmus. Urine was dark brown and (+) for
      protein and occult blood. Blood chemistry analysis revealed BUN 71 mg/dl,
      creatinine 6.8 mg/dl, CPK 143,850 IU and myoglobin 3,980 ng/ml. PRA on the 11th
      hospital day was 96 ng/ml/hour. This patient fulfilled the Levenson's diagnostic
      criteria for manifestations of neuroleptic malignant syndrome (NMS). High PRA did
      not decrease after cessation of the diuretics. After treatment with dantrolene
      sodium and 10 treatments with hemodialysis, azotemia disappeared with the start
      of diuresis. The PRA also decreased to the normal level. Characteristic
      acceleration of the central sympathetic stimuli in NMS seemed to have induced
      hyperreninemia, which together with rhabdomyolysis, might have contributed to the
      development of acute renal failure.

PMID- 7815750
TI  - [Changes in residual dextrose and amount of total protein loss in the effluent
      during the clinical course of continuous ambulatory peritoneal dialysis-related
      peritonitis].
AB  - Solute permeability of the peritoneum accelerates considerably in continuous
      ambulatory peritoneal dialysis (CAPD)-related peritonitis. Residual dextrose (RD)
      (g/bag) and the amount of total protein loss (LP) (g/bag) in the effluent of
      dialysate were measured during the clinical course of 21 cases of CAPD-related
      peritonitis as markers of deranged peritoneal permeability. The following were
      the results obtained: 1) In 15 cases of intraluminal infection (simple
      peritonitis by microorganism contamination through the lumen of a peritoneal
      catheter), RD decreased on day 1 (p < 0.001) and day 3 (p < 0.001) after the
      onset of peritonitis, and LP increased on day 1 (p < 0.001) and day 3 (p < 0.01),
      compared to the values of the non-infected phase. Both parameters were restored
      on day 7 and day 14 by adequate therapeutic maneuver. 2) In 6 cases of
      periluminal infection (peritonitis caused by an organic lesion of infection along
      the peritoneal catheter), RD and LP persisted even on day 7 (p < 0.01), and
      recovered 10 days after surgical removal of the peritoneal catheter with
      simultaneous catheter replacement. It is concluded that both RD and LP are
      valuable markers in the evaluation of the clinical course of CAPD-related
      peritonitis, and are useful in deciding on therapeutic intervention.

PMID- 7815751
TI  - [A case of ANCA-associated rapidly progressive glomerulonephritis with oral
      aphtha and erythema nodosum].
AB  - We reported a case of a 22-year old female with a microscopic form of
      polyarteritis nodosa (PN) who initially manifested Behcet's disease-like
      symptoms, such as fever, arthralgia, oral aphtha and erythema nodosum, and
      rapidly progressive glomerulonephritis (RPGN). On admission, her urinalysis
      showed active nephritic syndrome and her renal function rapidly deteriorated;
      serum creatinine levels elevated from 1.2 to 3.9 mg/dl within 2 weeks. Skin
      biopsy specimens from erythema showed panniculitis. Accordingly, she was treated
      with daily 30 mg of oral prednisolone and three-day intravenous pulse therapy of
      1000 mg of methylprednisolone twice. After treatment, skin eruption and oral
      aphtha disappeared, and the serum creatinine level improved to 1.2 mg/dl.
      Percutaneous renal biopsy performed on the 28th day showed focal necrotizing
      glomerulonephritis and hyalinosis of small arteries. Immunofluorescence studies
      showed only trace stainings for IgG, IgA and beta lc. Electron microscopic
      findings revealed fusion of the foot process and swelling of endothelial cells,
      but no dense deposits. Anti-neutrophil cytoplasmic antibody (ANCA) was positive
      for IgG class with a 40-fold titer by indirect immunofluorescence test and showed
      a cytoplasmic pattern combined with high urinary IL-8 level (280.1 pg/ml). We
      diagnosed this case as a microscopic form of PN. ANCA titer and urinary IL-8
      correlated positively with the disease activity, and were finally below 8-fold
      and 58.6 pg/ml, respectively after resolution of RPGN for 42 months. In this
      case, ANCA was useful not only for differential diagnosis of the patients with
      systemic vasculitis and crescentic glomerulonephritis, but also for evaluation of
      the disease activity.

PMID- 7815752
TI  - [A case of adenine phosphoribosyltransferase (APRT) deficiency discovered by
      urine examination].
AB  - APRT deficiency is an enzyme disorder which is inherited as an autosomal
      recessive trait. The use of adenine in purine metabolism is disturbed and it
      accumulates in the body, where it is oxidised by xanthine oxidase to poorly
      insoluble 2, 8-dihydroxyadenine (DHA). The dihydroxyadenine forms stones which
      cause recurrent urolithiasis, frequent episodes of urinary tract infection or
      interstitial nephritis, and finally renal insufficiency in some cases. We report
      a case of APRT deficiency discovered by urine examination. The patient was a 33
      year-old man who had never had any episodes of urolithiasis. He was admitted to
      our hospital because of pseudoarthrosis of his left arm caused by a traffic
      accident. His urinalysis revealed no proteinuria nor hematuria, but disclosed
      numerous round brown crystals in the sediment. These crystals had the
      characteristics of 2, 8-DHA. The enzyme activity of APRT in his blood was
      completely deficient. He was diagnosed as an APRT* QO homozygote. In addition,
      diagnostic imaging revealed that his right kidney was poorly hypoplastic and the
      pelvis of his left kidney was extra-renal. The renal function was slightly
      disturbed. In Japan 6 cases of 2, 8-DHA urolithiasis associated with hypoplastic
      kidney had been reported by 1989. Theoretically, the incidence of hypoplastic
      kidney is around 20% of all 2, 8-DHA urolithiasis cases. We suspect a genetic
      correlation between hypoplastic kidney and APRT deficiency. This patient was
      treated with Allopurinol, which inhibits the process of xanthine oxidation, after
      which crystals were no longer detected in his urine.

PMID- 7815753
TI  - [A case of idiopathic plasmacytic lymphadenopathy with polyclonal
      hyperimmunoglobulinemia associated with chronic nephritis].
AB  - A 48-year-old female who had general fatigue was admitted to our hospital. She
      had swelling of the axillary, inguinal, and paraaortic lymph nodes and
      mediastinal lesions. Laboratory examinations showed anemia, polyclonal
      hyperimmunoglobulinemia with IgG 5570 mg/dl, renal dysfunction and interstitial
      changes of the lungs. Microscopic findings of hematoxylin-eosin staining in
      biopsy specimens of the left inguinal and axillary lymph nodes revealed increased
      levels of infiltration of mature plasma cells without evidence of malignancy.
      Immunoperoxidase staining showed intracytoplasmic polyclonal immunoglobulin.
      These findings were identical to those of idiopathic plasmacytic lymphadenopathy
      with polyclonal hyperimmunoglobulinemia (IPL) described by Mori et al. (1980).
      The specimens also showed evidence of chronic nephritis with infiltration of
      lymph cells and a slight invasion of plasma cells. Accordingly this case was
      diagnosed as IPL with renal involvement, which is associated with chronic
      nephritis. Recently, five cases of IPL with renal dysfunction have been reported.
      In particular, two cases of IPL with renal dysfunction, which included our case,
      revealed an increased level of IL6. These findings suggest that the occurrence of
      renal involvement with IPL may be related to changes in IL6, which is an
      important factor in the pathogenesis of IPL.

PMID- 7815754
TI  - [Two cases of membranous glomerulonephritis associated with hepatitis C virus
      infection].
AB  - Although the occasional occurrence of glomerulonephritis associated with
      hepatitis C virus (HCV) infection has been reported recently in the literature,
      the type described has been mainly membranoproliferative glomerulonephritis
      (MPGN); membranous glomerulonephritis (MGN) is very rare. In this paper, two
      cases of MGN associated with HCV infection are reported. Case 1 was a 56-year-old
      male who had positive HCV Ab and HCV RNA. The diagnosis of chronic active
      hepatitis was verified by liver biopsy. Laboratory data showed proteinuria (5g
      per day), hematuria and hypocomplementemia by hemolytic assay. Renal biopsy led
      to the diagnosis of MGN in stage II. The patient was treated with interferon
      alpha for 6 months, resulting in improvement of hypocomplementemia, transient
      reduction of GOT and GPT during the course of treatment. The GOT and GPT were
      aggravated again after the completion of therapy. No improvement was seen in
      proteinuria and hematuria, and HCV Ab remained positive. Case 2 was a 69-year-old
      male who had positive HCV Ab and HCV RNA, and had normal liver function.
      Subsequently, his GOT value was slightly elevated. Proteinuria (2g per day) was
      demonstrated. The diagnosis of MGN in stage II was made on the basis of renal
      biopsy. The clinical characteristics of these two cases suggest that MGN is a
      type of glomerulonephritis associated with HCV infection.

PMID- 7815755
TI  - [Effect of nasal CPAP on human diaphragm position and lung volume].
AB  - The cephalic margin of the zone of apposition (ZOA) was observed with
      ultrasonography at ambient pressure and during nasal continuous positive airway
      pressure (nasal CPAP) in nine awake healthy males in a supine position. In a
      relaxed state at ambient pressure, there was a significant (p < 0.001) linear
      relationship between lung volume and the movement of the cephalic margin of the
      ZOA over the range from maximum expiratory position (MEP) to maximum inspiratory
      position (MIP). With nasal CPAP, functional residual capacity increased
      significantly (p < 0.01) in proportion to the increase in CPAP. At 20 cmH2O CPAP,
      the mean increase in volume at end expiration was 36% of the vital capacity
      measured at ambient pressure. The cephalic margin of the ZOA moved significantly
      (p < 0.01) in a caudal direction as CPAP was increased. At 20 cmH2O CPAP, the
      cephalic margin of the ZOA at end expiratory position (EEP) had moved 55% of the
      difference from MIP to MEP measured at ambient pressure. The end expiratory
      diaphragm position during nasal CPAP was lower than the diaphragm position at
      ambient pressure when lung volumes were equal. These results suggest that during
      nasal CPAP the chest wall is distorted from its relaxed configuration, with a
      decrease in rib cage expansion and an increase in outward displacement of the
      abdominal wall.

PMID- 7815756
TI  - [Prognosis of idiopathic interstitial pneumonia].
AB  - Idiopathic interstitial pneumonia (IIP) is characterized by chronic inflammation
      and fibrosis of the lung. It carries a poor prognosis and the treatment for IIP
      has not yet been established. We evaluated 116 cases of IIP retrospectively, and
      analyzed possible prognostic factors, such as the mode of detection, clinical
      symptoms, chest X-ray findings, pulmonary function tests, blood chemistry,
      bronchoalveolar lavage (BAL), and treatments. The 5-year survival rate from the
      onset was 39.5% and the 10-year survival rate was only 12.7%. The 5-year survival
      rate from the appearance of dyspnea on exertion was 23.2% and 10-year survival
      rate was 9.0%. According to the results of the Kaplan-Meier analysis, patients
      with low% FVC (< 70%), those with high values of ESR, those with high values of
      CRP, and those with advanced chest X-ray shadows did not survive as long as other
      patients. Multivariate analysis with a proportional hazards model revealed that a
      high percentage of eosinophils in BALF was associated with a poor prognosis.
      Analysis with a logistic model revealed that being male having a low %DLCO were
      associated with a poor prognosis.

PMID- 7815757
TI  - [Clinical and serological studies in six cases of chlamydial pneumonia].
AB  - Clinical and serological studies of chlamydial pneumonia were done in six
      patients (three men and three women). The other three patients had no avian
      contact and showed almost the same clinical symptom. Acute infection with
      Chlamydia psittaci and Chlamydia pneumoniae were diagnosed in two patients and in
      one patient, respectively, by MFA. Because in some cases Chlamydia psittaci
      pneumonia and Chlamydia pneumoniae pneumonia are difficult to differentiate, it
      is necessary to use a test that allows different chlamydia species to be
      distinguished.

PMID- 7815758
TI  - [Bronchial hyperresponsiveness and relaxability in patients with mitral
      stenosis].
AB  - To study the differences in bronchial responsiveness to inhaled methacholine and
      salbutamol between patients with mitral valve disease those with bronchial asthma
      a bronchial provocation test (Astograph) and pulmonary function tests were done
      in 25 patients with mitral stenosis (MS) and 18 patients with bronchial asthma
      (BA). We derived an index of airway reloxability from the effect of salbutamol
      after precontraction with inhaled methacholine. This index was the change in
      respiratory conductance (Grs) over time during inhalation of salbutamol (SGrs-d).
      It was computed as SGrd = delta Grs/delta t. Eighteen patients with MS (72%)
      showed bronchial hyperresponsiveness (BHR) to methacholine. The MS patients with
      BHR (MS(+)) had lower values of the ratio of the forced expiratory volume in one
      second to the forced vital capacity (FEV/FVC) and maximal expiratory flow at 25%
      of vital capacity (V25) than MS patients without BHR (MS(-)). There was a
      significant correlation between V25 and the log cumulative dose producing a 35%
      decrease in respiratory conductance (PD35Grs) in MS(+). The mean log Dmin of
      MS(+) was significantly higher than that of the patients with BA (0.14 +/- 0.64
      log units and -0.30 +/- 0.65 log units, p < 0.05, respectively). The mean log
      PD35Grs of MS(+) was also significantly higher than that of the patients with BA
      (1.09 +/- 0.53 log units and 0.45 +/- 0.66 log units, p < 0.01, respectively).
      Indices of relaxability (SGrs-d and SCrs-d/Grs-d) in MS(+) were significantly
      lower than in BA patients. Indices of hyperresponsiveness and relaxability were
      both significantly lower in patients with MS than in patients with BA.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7815759
TI  - [Cell-to-cell interaction in airway mucosa--effect of eosinophils on airway
      epithelial ion transport].
AB  - We examined the interaction between eosinophil-derived mediators and ion
      transport in airway epithelial cells. Eosinophils were obtained by peritoneal
      lavage from polymyxin B-treated guinea-pigs and were purified over discontinuous
      Percoll density gradients. The activated eosinophil supernatant was prepared with
      a two-stage method in the presence of A23187. The effects of eosinophil
      supernatant on the electric properties of cultured epithelial cells from cow
      trachea were examined in an Ussing chamber under short-circuit conditions. The
      eosinophil supernatant added to the serosal and mucosal sides increased the short
      circuit current (Isc) in an eosinophil number-dependent manner (3 x 10(6), 10(7)
      eosinophils: delta Isc 9 +/- 1 microA/cm2, 18 +/- 3 microA/cm2). The response was
      inhibited by treatment of epithelial cells with diphenylamine-2-carboxylate but
      not by amiloride. The increase in Isc induced by the supermatant from eosinophils
      treated with indomethacin or the lipoxygenase inhibitor AA861 was significantly
      less than that induced by untreated eosinophils. These results indicate that
      activated eosinophils stimulate C1 secretion in airway epithelium via release of
      metabolites of arachidonic acid.

PMID- 7815760
TI  - [A case of limited Wegener's granulomatosis with hemophilia A, complicated by
      empyema, bronchopleural fistula and herpes zoster during therapy].
AB  - A 36-year-old man with hemophilia A was admitted to hospital because of otalgia,
      hearing loss, nasal obstruction, nonproductive cough, and high fever. His
      laboratory data showed high-grade acute inflammatory reactions. His chest X-ray
      and CT films showed multiple cavitary masses in the right lower lung field.
      Bronchoscopy performed at our institution revealed bronchial nodules in the
      intermediate truncus, and BAL revealed increases in the neutrophils and an IgG
      index (BAL IgG/albumin divided by serum IgG/albumin). Biopsy specimens obtained
      from nasal mucosa showed epithelioid granulomas with Langerhans' giant cells and
      necrotizing vasculitis. Antineutrophil cytoplasmic antibodies were also positive,
      but no evidence of glomerulonephritis was observed. The diagnosis of limited
      Wegener's granulomatosis was thus made. He was treated with standard therapy
      (daily cyclophosphamide and glucocorticoids), but within 1 month he had
      complications of empyema with herpes zoster, and bronchopleural fistula. The
      complications resolved with appropriate treatment.

PMID- 7815761
TI  - [A case of severe pneumonia in an elderly man, caused by Citrobacter freundii
      suspected to have a low susceptibility to imipenem/cilastatin sodium].
AB  - An 80-year-old blind man with lepromatous leprosy suffered from right femoral
      neck and humeral neck fractures on July 9, 1993. Because of fever (38.6 degrees
      C), difficult expectoration and diffuse bilateral perihilar infiltrates with
      consolidation in the left lower lung field on his chest radiograph, severe
      pneumonia was diagnosed. With intravenous hyperalimentation, imipenem/cilastatin
      (IPM/CS), ceftazidime, minocycline, gentamicin (GM), and human immunoglobulin
      were administrated. On July 29, hip screw-plate fixation was done. Citrobacter
      freundii was isolated from the sputum and its susceptibility was IPM/CS+, GM3+.
      Multi-drug therapy with GM and other antibiotics improved the patients'
      condition, but Citrobacter freundii were still detected and 43 days of medication
      were needed. According to a report by the Ministry of Health and Welfare in 1992,
      the resistance rate of IPM/CS against Citrobacter freundii is only 0.7%, and
      IPM/CS is more effective than beta-Lactams. This is a very rare case of severe
      pneumonia in an elderly patient caused by Citrobacter freundii that was suspected
      to have low susceptibility to IPM/CS.

PMID- 7815762
TI  - [A case of Fusobacterium necroforum sepsis].
AB  - A 26-year-old man was admitted to our hospital with a 10-day history of sore
      throat, high fever, and right knee joint pain. On physical examination, the
      pharynx was considerably inflamed, and the right knee joint was swollen and
      extremely tender. Chest radiography showed multiple, bilateral nodules and masses
      with pleural effusions. Fusobacterium necorforum grew from samples of blood,
      pleural effusion, and pus taken from the knee joint. The patient was treated with
      intravenous clindamycin, ventilatory support, and continuous chest and knee joint
      drainage. His condition progressively improved and he was discharged on the 66th
      hospital day. A disease caused by an oropharyngeal infection with secondary
      suppurative thrombophlebitis of the internal jugular vein, and complicated by
      multiple metastatic infections is called postanginal septicemia, or Lemierre
      syndrome. Before the discovery of antibiotics, this disease usually was fatal.
      The widespread use of antibiotics for treat oropharyngeal infections may have
      caused a number of reported cases. Lemierre syndrome is an uncommon complication
      of oropharyngeal infection, and it may be fatal if diagnosis is delayed. Careful
      attention must be directed to patients with oropharyngeal infection who have
      signs and symptoms that suggest metastatic infection.

PMID- 7815763
TI  - [A case of bronchial asthma associated with reflux esophagitis, whose peak
      expiratory flow rate improved with omeprazole and cisapride].
AB  - A 60-year-old male had visited our hospital periodically, because of perennial
      moderate atopic asthma, since 53 years of age. His symptoms had stabilized
      following treatment with oral theophylline 400 mg, tranilast 300 mg and
      inhalation of beclomethasone dipropionate 400 micrograms and procaterol
      hydrochloride. His peak expiratory flow rate early in the morning was 465 L/min,
      %VC was 115% and FEV1.0% was 62.4% in May of 1993. On May 24, 1993, though he had
      no gastrointestinal symptoms, gastrointestinal fiberscopy revealed a hiatal
      hernia, reflux esophagitis and active gastroduodenal ulcer. The upper
      gastrointestinal x-ray films showed gastroesophageal reflux. Therefore, we
      diagnosed bronchial asthma associated with reflux esophagitis and gastroduodenal
      ulcer. He was started on omeprazole, as a proton pump inhibitor (PPI), and
      cisapride. After the treatment with PPI and cisapride, his peak expiratory flow
      rate early in the morning and in the evening, %VC and FEV1.0 increased. Three
      months later gastrointestinal fiberscopy revealed improvement in the reflux
      esophagitis and the gastroduodenal ulcer. We speculate that the improvement in
      the peak expiratory flow rate is related to that of the gastroesophageal reflux.

PMID- 7815764
TI  - [A case of life-threatening acute asthma with marked elevation of serum
      theophylline level during inhalational anesthesia].
AB  - A 21-year-old man was admitted to our hospital because of life-threatening acute
      asthma. His condition deteriorated while he was receiving aminophylline and high
      dose corticosterolids, and complicated by pneumomediaststinum. He was intubated
      and ventilated mechanically. Since peak inspiratory pressure was very high and
      arterial blood gases were not improving, he was treated with inhaled haltohane
      and enflurane, and bronchial lavage was done via a bronchoscope. Anesthesia
      continued for 114 hours before his condition improved. The serum theophylline
      levels were elevated during anesthesia. Since the dose of aminophylline was not
      very high, this elevation may have been related to the inhalation of halothane
      and enflurane.

PMID- 7815765
TI  - [A case of malignant fibrous histiocytoma in the mediastinum].
AB  - A 81-year-old man was admitted to the hospital because he complained of
      hoarseness. Chest radiography showed a mass in the right upper mediastinum. An
      operation was done to remove the mass and make a conclusive diagnosis.
      Histologically, the tumor tissue consisted of spindle-shaped fibroblast-like
      cells and round histiocyte-like cells with bizarre giant cells. Part of the
      tissue had a storiform pattern. These findings led a diagnosis of malignant
      fibrous histiocytoma (MFH) of the "usual type". MFH is known to occur frequently
      in the soft tissues of extremities, trunk, and retroperitoneum, but it is seldom
      detected in the mediastinum. We report here a rare case of primary MFH in the
      mediastinum.

PMID- 7815766
TI  - [A case of mediastinal parathyroid adenoma diagnosed by transtracheal needle
      aspiration].
AB  - Chest radiography of a 73-year-old man with upper abdominal pain showed
      hypercalcemia and an upper mediastinal mass. Functional mediastinal parathyroid
      adenoma was diagnosed, because of abnormally high levels of PTH in his serum and
      in fluid collected by transtracheal needle aspiration from the mediastinal mass.
      We resected the adenoma operatively. It a cystic tumor located behind the
      superior vena cava and the trachea. The inferior end of the tumor was as low as
      the aortic arch, and superiorly the tumor was attached to the inferior pole of
      the thyroid gland by a vascular pedicle. Histologically adenoma cells were
      predominant. This tumor was a mediastinal parathyroid adenoma by location, but
      because it was attached to the thyroid gland superiorly, it may have originated
      from the superior parathyroid gland and then descended because of its weight into
      the posterior superior mediastinum. Thus, it cannot be considered an ectopic
      parathyroid adenoma in origin. Mediastinal parathyroid adenoma is a rare disease,
      and these tumors are usually so small that correct localization of the adenoma is
      often difficult even by CT scan or scintigram. This is the first reported case of
      a mediastinal parathyroid adenoma that appeared as a mediastinal mass on a plain
      chest radiography and in which the level of PTH in the fluid collected from the
      mass by transtracheal needle aspiration was high.

PMID- 7815768
TI  - [Intrabullar suction-adhesion in a case of giant bulla of the lung with steroid-
      department intractable bronchial asthma].
AB  - We successfully reduced a giant bulla using an intrabullar suction-adhesion
      method in a case of steroid-dependent intractable bronchial asthma. A 53-year-old
      woman was hospitalized with an asthma attack, and suffered pneumonia in the area
      surrounding a giant bulla after remission of two episodes of asthma. After the
      pneumonia, we found that the giant bulla had increased in volume. It was readily
      apparent that the bulla should be reduced. At that time a right side pneumothorax
      occurred by accident, which improved the chest drainage. Immediately after that,
      we inserted a chest drainage tube directly into the bulla and instilled fibrin
      glue through the tube into the bulla. Intrabullar suction and bronchial
      embolization via bronchofiberscopy has been used to patients with inoperable
      giant bullae of the lung. If intrabullar suction with fibrin glue alone can
      reduce giant bulla, it would offer another option to patients with inoperable
      giant bullae without the risk of a surgical procedure.

PMID- 7815767
TI  - [A case of pulmonary alveolar proteinosis with high levels of tumor markers].
AB  - We report a case of pulmonary alveolar proteinosis (PAP) in which the serum
      levels of CEA, CA15-3, and TPA, as well as the whole lung lavage fluid levels of
      CEA, CA19-9, CA125, CA15-3, CA50, SLX, SCC, and TPA were high. The patient was a
      39-year-old man who presented with exertional dyspnea, and nonsegmental bilateral
      reticular infiltration shadows in the middle and lower lung fields on the chest
      radiograph. A diagnosis of proteinosis was confirmed by histopathology of the
      transbronchial lung biopsy (TBLB) specimen, biochemical analysis of the
      phospholipids, and an electron microscopic study of lavage fluid. Whole lung
      lavages alleviated his symptoms, effaced the shadows on the chest radiographs and
      brought the blood gas values closer to normal. An immunohistochemical study of
      TBLB specimens showed that CEA, CA153, and SLX were positively stained in the
      alveolar epithelia. With repeated lavage, tumor markers (CEA, CA15-3, TPA) in the
      fluid decreased. These results suggest that the alveolar epithelia indeed
      produced these tumor marker molecules. In PAP, it is well recognized that CEA may
      be high in at least one of the following: serum, bronchoalveolar lavage fluid,
      and whole lung lavage fluid. To date, however, the site of production of such
      tumor markers had not been clearly demonstrated to be in the lung tissue. This
      case is interesting because there are few reports of PAP with high levels of
      tumor markers in the serum and whole lung lavage fluid, and because the tumor
      markers found in abnormally high amounts in this patient were produced by
      alveolar epithelia.

PMID- 7815769
TI  - [Small cell lung cancer presenting as a metastatic conjunctival tumor].
AB  - A 65-year-old man complaining of a left medial ocular angle mass and hemoptysis
      was admitted to our hospital. Chest radiography revealed a right hilar mass and
      bronchoscopy revealed widespread cancerous invasion of the carina, both main
      bronchi, right upper lobe bronchus, truncus intermedius, and middle lobe
      bronchus. Histological examination of a biopsied specimen revealed small cell
      carcinoma. Brain CT scan, abdominal CT scan, and bone scintigram showed solitary
      brain, multiple liver, and multiple bone metastases. Partial response was
      obtained with three courses of combined chemotherapy with carboplatin and
      etoposide, and the ocular tumor until it was almost invisible to the unaided eye.
      However, complete response could not be obtained with additional two courses of
      combined chemotherapy, and the patient was discharged. Seven months after the
      first admission, he was readmitted with dyspnea and an enlarged (6 mm in
      diameter) left ocular mass. Histological examination of the resected mass
      revealed a small cell carcinoma that had metastasized to the conjunctival
      substantia propria. He died of respiratory failure one month after readmission.
      Metastasis to the eye from primary lung cancer is uncommon and patients such as
      this are extremely rare. Although some cases of uveal or orbital metastasis from
      lung cancer have been reported, we can find no other report of conjunctival
      metastasis from lung cancer.

PMID- 7815770
TI  - [A case of sarcoidosis with systemic lymph node involvement presenting as
      multiple high-density masses on chest and abdominal CT].
AB  - We report a case of sarcoidosis with mediastinal and abdominal lymph node
      involvement presenting as multiple high-density masses on chest and abdominal CT.
      The patient was a 43-year-old housewife who came to our hospital because of a dry
      cough and exertional dyspnea. A chest radiograph showed bilateral diffuse
      reticulo-nodular shadows and widening of the mediastinum. On CT of the chest and
      the abdomen, lymph nodes were swollen throughout the mediastinum and the para
      aortic area of the abdomen. They appeared as very-high-density masses on plain
      CT. Bronchoscopy revealed involvement of the bronchial walls. Punch biopsy of the
      bronchial wall, TBLB, and biopsy of the anterior mediastinal lymph node all
      revealed non-caseous epithelioid cell granulomas. These granulomas contained
      lamellated, irregularly shaped and darkly-stained structures (Schaumann bodies)
      that caused the high density of the involved lymph nodes on CT. This case shows
      at least a part of the mechanism of calcification of lymph node lesions in
      patients with sarcoidosis.

PMID- 7815771
TI  - The Drug Enforcement Agency and DEA Form 104.

PMID- 7815772
TI  - The elusive paperless medical record.

PMID- 7815773
TI  - Meningococcal disease in Kansas, 1990-1993.

PMID- 7815774
TI  - Primary care approach to the newly diagnosed HIV-positive patient.

PMID- 7815775
TI  - Cervical spondylotic myelopathy: a cause of gait disturbance and falls in the
      elderly.
AB  - Cervical spondylosis is a very common disorder in the elderly that leads to
      osteophyte formation and degenerative disc disease. Compression of the cervical
      cord and nerve roots can occur in a small number of patients, often dependent
      upon a congenitally narrow canal. Cord compression produces progressive spastic
      paraparesis, frequently asymmetric, and often accompanied by paresthesias and
      sensory loss in the feet and hands. The course is quite variable. Often, symptoms
      are mild and do not progress. Such cases are best treated conservatively with a
      cervical collar and physical therapy. Elderly patients often experience
      progression of symptoms and more serious neurologic impairment. Surgery should be
      recommended to arrest progression of myelopathic symptoms in patients whose
      general condition is satisfactory.

PMID- 7815776
TI  - Immunization of healthy adults.

PMID- 7815777
TI  - Diagnosis and non-operative treatment of pseudoaneurysm complicating arterial
      puncture.

PMID- 7815778
TI  - Is precordial percussion worthwhile?

PMID- 7815779
TI  - The word.

PMID- 7815780
TI  - Disease conditions of canine anal sacs.
AB  - The literature about the anal sacs of healthy dogs and the pathogenesis,
      diagnosis and therapy of anal sac impaction and sacculitis are reviewed.
      Knowledge about the physiological role of the anal sacs is still confusing. The
      colour and consistency of the anal sac contents are variable in healthy dogs and
      there are no pathognomonic signs of anal sac impaction or sacculitis. The wide
      variation in macroscopic detail of anal sac secretions may give rise to
      misinterpretation and thus overdiagnosis of sacculitis. Other diseases such as
      vaginitis, flea allergy, atopy, proctitis, parasites and perianal fistulae can
      lead to similar signs and must be eliminated from the differential diagnosis
      before the anal sacs are incited as the cause of the signs. Further research is
      necessary on the morphological, physical and biochemical aspects of the anal sacs
      and their secretions to define more precise criteria for the diagnosis of
      impaction and sacculitis. It is imperative that controlled therapeutic trials
      should be performed, and such studies are indispensable for the rational therapy
      of anal sac disease.

PMID- 7815781
TI  - Multisystemic inflammatory disease in a borzoi dog.
AB  - A six-week-old female borzoi puppy from a brother-sister mating developed a
      generalised illness characterised by anorexia, temporary intention tremor,
      episodic pyrexia, tachypnoea, conjunctivitis, otitis and neck pain.
      Haematological abnormalities included an inflammatory leukogram and regenerative
      anaemia. Blood cultures remained sterile; clinical chemistry values were
      unremarkable. The puppy had recurrent seizures and was euthanased when 18 weeks
      old. Post mortem examination revealed a multisystemic inflammatory disease
      involving thyroids, lymph nodes, spleen, pancreas, bladder and lung, but no
      lesions to account for the neurological signs. The cause of this generalised
      disease was not recognised. The histological features are unusual and resemble
      those described in other dogs of this breed.

PMID- 7815782
TI  - Aural cholesterol granuloma in a dog.
AB  - A five-year-old female Irish setter was referred for surgery for a left-sided
      aural mass. The dog was generally well, but had signs of left-sided otalgia for
      one week. Biopsy identified the lesion as a cholesterol granuloma. The mass was
      removed three weeks later by a total canal ablation/lateral bulla osteotomy. The
      dog recovered from surgery without any complications. Ten months later, there was
      no evidence of recurrence. The purpose of this paper is to report the clinical
      and histopathological findings of this unusual form of granuloma which has not
      previously been reported in the canine ear.

PMID- 7815783
TI  - What is your diagnosis? Feline hepatic encephalopathy secondary to a congenital
      portosystemic shunt.

PMID- 7815784
TI  - Efficacy of daily amitraz on generalised demodicosis in dogs.
AB  - Fifty dogs with generalised demodicosis were treated with daily applications of
      0.125 per cent amitraz solution over half the body. This was applied once a day,
      alternating the body half treated. Nine dogs were lost to follow-up; the
      remaining dogs were classified as either a success (25 dogs, 61 per cent) or a
      failure (16 dogs, 39 per cent) according to their response to treatment. Eight of
      the failures were due to persistent demodicosis and eight relapsed within one
      year after treatment. All eight of the relapsed dogs were cured after a second
      course of daily amitraz treatment. For the 25 dogs considered treatment
      successes, the median duration of treatment was 6.5 weeks (range, three weeks to
      nine months), and the median interval from completion of treatment to last post
      treatment evaluation was 3.4 years (range, two to four-and-a-half-years).
      Including the eight dogs that were cured after retreatment, the daily amitraz
      applications were curative in 33 of 41 dogs (80 per cent) with generalised
      demodicosis.

PMID- 7815785
TI  - Bodyweight and feed intake of German shepherd bitches during pregnancy and
      lactation.
AB  - Thirty German shepherd bitches were assessed for weekly changes in bodyweight,
      daily food intake and litter size during pregnancy and lactation. The weekly
      changes in food intake and bodyweight were divided into two and three phases,
      respectively. Linear regression equations were used to fit each phase. The
      bodyweight of the bitches at mating ranged between 17 and 36 kg. The same diet
      was used for all the bitches throughout the study. Despite the tendency that
      litter size, birthweight and bodyweight of the puppies at three and six weeks
      increased with age of the bitch, no significant differences could be found.
      Significant (P < 0.05) bodyweight differences existed at mating between the age
      groups. High correlations existed between mating weight and weight at 60 days of
      pregnancy (r2 = 0.94) and between mating weight and weaning weight (r2 = 0.89) of
      the litter. It was possible to successfully establish performance criteria for
      the reproductive German shepherd bitch in a commercial breeding unit, which can
      be used as a baseline to improve diets and feeding programmes by means of dietary
      manipulations.

PMID- 7815786
TI  - Bilateral pneumectomy (volume reduction) for chronic obstructive pulmonary
      disease.
AB  - We undertook surgical bilateral lung volume reduction in 20 patients with severe
      chronic obstructive pulmonary disease to relieve thoracic distention and improve
      respiratory mechanics. The operation, done through median sternotomy, involves
      excision of 20% to 30% of the volume of each lung. The most affected portions are
      excised with the use of a linear stapling device fitted with strips of bovine
      pericardium attached to both the anvil and the cartridge to buttress the staple
      lines and eliminate air leakage through the staple holes. Preoperative and
      postoperative assessment of results has included grading of dyspnea and quality
      of life, exercise performance, and objective measurements of lung function by
      spirometry and plethysmography. There has been no early or late mortality and no
      requirement for immediate postoperative ventilatory assistance. Follow-up ranges
      from 1 to 15 months (mean 6.4 months). The mean forced expiratory volume in 1
      second has improved by 82% and the reduction in total lung capacity, residual
      volume, and trapped gas has been highly significant. These changes have been
      associated with marked relief of dyspnea and improvement in exercise tolerance
      and quality of life. Although the follow-up period is short, these preliminary
      results suggest that bilateral surgical volume reduction may be of significant
      value for selected patients with severe chronic obstructive pulmonary disease.

PMID- 7815787
TI  - Incidence of local recurrence and second primary tumors in resected stage I lung
      cancer.
AB  - From 1973 to 1985, 598 patients underwent resection for stage I non-small-cell
      lung cancer. There were 291 T1 lesions and 307 T2 lesions. The male/female ratio
      was 1.9:1. The histologic type was squamous carcinoma in 233 and nonsquamous
      carcinoma in 365. Lobectomy was performed in 511 patients (85%), pneumonectomy in
      25 (4%), and wedge resection or segmentectomy in 62 (11%). A mediastinal lymph
      node dissection was carried out in 560 patients (94%) and no lymph node
      dissection in 38 (6%). Fourteen postoperative deaths occurred (2.3%). Ninety-nine
      percent of the patients were observed for a minimum of 5 years or until death
      with an overall median follow-up of 91 months. The overall 5- and 10-year
      survivals (Kaplan-Meier) were 75% and 67%, respectively. Survival in patients
      with T1 N0 tumors was 82% at 5 years and 74% at 10 years compared with 68% at 5
      years and 60% at 10 years for patients with T2 tumors (p < 0.0004). The overall
      incidence of recurrence was 27% (local or regional 7%, systemic 20%) and was not
      influenced by histologic type. Second primary cancers developed in 206 patients
      (34%). Of these, 70 (34%) were second primary lung cancers. Despite complete
      resection, 31 of 62 patients (50%) who had wedge resection or segmentectomy had
      recurrence. Five- and 10-year survivals after wedge resection or segmentectomy
      were 59% and 35%, respectively, significantly less than survivals of those
      undergoing lobectomy (5 years, 77%; 10 years, 70%). The 5- and 10-year survivals
      in the 38 patients who had no lymph node dissection were reduced to 59% and 32%,
      respectively. Apart from the favorable prognosis observed in this group of
      patients, three facts emerge as significant: (1) Systematic lymph node dissection
      is necessary to ensure that the disease is accurately staged; (2) lesser
      resections (wedge/segment) result in high recurrence rates and reduced survival
      regardless of histologic type; and (3) second primary lung cancers are prevalent
      in long-term survivors.

PMID- 7815788
TI  - Functional comparison between the human inferior epigastric artery and internal
      mammary artery. Similarities and differences.
AB  - Although the inferior epigastric artery has been used as an alternative arterial
      graft for coronary artery bypass grafting, little is known about the contractile
      and relaxation characteristics of this artery. This study was designed to compare
      the pharmacologic reactivity of the two arterial conduits--the inferior
      epigastric artery and the internal mammary artery. Forty-one inferior epigastric
      artery ring segments from eight patients undergoing coronary grafting and 62
      internal mammary artery ring segments were set up in organ baths under
      physiologic pressure. The contractility was determined from the contraction
      induced by the depolarizing agent potassium and receptor-mediated vasoconstrictor
      agents, norepinephrine, U46619, and endothelin-1. Endothelium-dependent
      relaxation was induced by the calcium ionophore A23187, a non-receptor agonist
      for endothelium-derived relaxing factor, and acetylcholine, a receptor agonist
      for endothelium-derived relaxing factor. Glyceryl trinitrate was used to study
      endothelium-independent relaxation. The maximal response (either contraction or
      relaxation) and the effective concentration causing 50% of the maximal response
      for these two arteries were compared. There was no difference (p > 0.05) either
      in the maximal contraction force (5.30 +/- 0.87 versus 4.76 +/- 0.89 gm for
      potassium, 5.13 +/- 0.67 versus 4.47 +/- 1.15 gm for norepinephrine, 8.04 +/-
      1.23 versus 6.23 +/- 0.99 gm for U46619, and 4.88 +/- 0.69 versus 5.57 +/- 0.93
      for endothelin-1 (n = 6 to 10 for each vasoconstrictor) or in the maximal
      relaxation induced by glyceryl trinitrate (86.46% versus 92.98%, n = 6) or by
      acetylcholine (20.72% versus 45.51%, n = 5) between the inferior epigastric
      artery and internal mammary artery. The effective concentration causing half
      maximal response to all vasoconstrictors and vasodilators was similar between the
      two arteries (p > 0.05). However, A23187 induced significantly less relaxation in
      the inferior epigastric artery (38.42 +/- 15.49%, n = 6) than in the internal
      mammary artery (71.89 +/- 7.17%, n = 9, p < 0.05). We conclude that
      contractility, endothelium-independent relaxation, and receptor-mediated
      endothelium-dependent relaxation are similar in the inferior epigastric artery
      and the internal mammary artery. However, the endothelium of this arterial graft
      has less ability to respond to the non-receptor-mediated endothelium-derived
      relaxing factor stimulant. The influence of this difference on the prevalence of
      atherosclerosis and long-term patency rate in the inferior epigastric artery
      remains to be studied.

PMID- 7815789
TI  - Carcinoma of the esophagus. Prognostic significance of histologic type.
AB  - Previous investigators have reported that in patients with esophageal carcinoma
      tumor cell type affects prognosis. A retrospective analysis of 258 patients, from
      1985 to 1991, undergoing curative esophagogastrectomy for adenocarcinoma (n =
      134) or squamous cell carcinoma (n = 124) was performed to test the hypothesis
      that histologic cell type is an independent prognostic factor and to identify
      other predictors of survival after resection. The actuarial overall survival (p =
      0.16) and disease-specific survival (p = 0.68) were similar for adenocarcinoma
      (median overall survival = 27 months) and squamous cell carcinoma (median overall
      survival = 22 months). Univariate analysis identified T stage, N stage, number of
      diseased nodes, tumor differentiation, tumor site, and blood transfusions as
      significant (p < 0.05) variables in predicting overall survival. The presence of
      Barrett's esophagus was not predictive of survival. Multivariate analysis
      demonstrated that T stage (p = 0.006), N stage (p = 0.01), and number of diseased
      lymph nodes (p = 0.03) were independent predictors of overall survival. This
      analysis demonstrated that histologic type is not an independent variable for
      overall survival in patients undergoing curative esophagogastrectomy for
      carcinoma of the esophagus and gastroesophageal junction. Outcome is most
      strongly influenced by extent of disease defined by T and N stage.

PMID- 7815790
TI  - Intrathoracic esophageal perforation. The merit of primary repair.
AB  - Between 1976 and 1993, 22 patients with intrathoracic esophageal perforations,
      none associated with carcinoma, underwent primary repair regardless of the
      interval between perforation and the time of repair. Eighteen perforations were
      iatrogenic and four were spontaneous. The interval from perforation to operation
      was less than 12 hours in 10 patients, 12 to 24 hours in 3, and more than 24
      hours in 9. Principles of repair included (1) a local esophagomyotomy proximal
      and distal to the tear to expose the mucosal defect and normal mucosa beyond, (2)
      debridement of the mucosal defect and closure over a bougie, and (3)
      reapproximation of the muscle. The repair was buttressed with muscle or pleura in
      five patients. Associated distal obstruction caused by reflux stricture was
      treated with dilation and fundoplication in four patients. Of the four patients
      with achalasia, two underwent esophagomyotomy with a fundoplication and one
      underwent myotomy alone. There was one death. The esophageal repair healed
      primarily in 17 patients (80%). Four patients, three of whom underwent repair
      more than 24 hours after the perforation, had leaks at the site of repair. All
      four fistulas eventually healed with drainage alone, two with simple tube
      thoracostomy and two with rib resection and empyema tube placement. In the
      absence of cancer or an irreversible distal obstruction, meticulous repair of an
      intrathoracic esophageal perforation is the preferred approach, regardless of the
      duration of the injury, inasmuch as primary healing is likely, and the morbidity
      associated with prolonged drainage or diversion may be avoided.

PMID- 7815791
TI  - Critical aortic stenosis in the neonate. A comparison of balloon valvuloplasty
      and transventricular dilation.
AB  - The optimal treatment of critical aortic stenosis in the neonate and infant
      remains controversial. We compared transventricular dilation using normothermic
      cardiopulmonary bypass and percutaneous balloon aortic valvuloplasty with respect
      to early and late survival, relief of aortic stenosis, degree of aortic
      insufficiency, left ventricular function, and freedom from reintervention.
      Between July 1987 and July 1993, 30 neonates and infants underwent
      transventricular dilation or balloon aortic valvuloplasty for critical aortic
      stenosis. The patients in the transventricular dilation group (n = 21) ranged in
      age from 1 to 59 days (mean age 18.0 days +/- 19.1 days) and the balloon aortic
      valvuloplasty group (n = 9) from 1 to 31 days (mean age 10.0 days +/- 9.0 days).
      There were no significant differences in weight, body surface area, or aortic
      anulus diameter between the two groups (p = 1.0). Associated cardiovascular
      anomalies were more common in the transventricular dilation group (48%) than in
      the balloon aortic valvuloplasty group (11%). After intervention, the degree of
      residual aortic stenosis and insufficiency was equivalent in the two groups as
      assessed by postprocedural Doppler echocardiography. Ejection fraction improved
      within both groups (transventricular dilation 39% +/- 20.2% versus 47% +/- 22.0%;
      balloon aortic valvuloplasty 51% +/- 16.1% versus 62% +/- 8.4%), and there was no
      significant difference between groups. The left ventricular mass/volume ratio
      increased within both groups (p < 0.05) but with no significant difference
      between groups (transventricular dilation 1.4 +/- 0.5 gm/ml versus 1.8 +/- 0.6
      gm/ml; balloon aortic valvuloplasty 1.1 +/- 0.6 gm/ml versus 1.7 +/- 0.4 gm/ml).
      Early mortality in the transventricular dilation group was 9.5% and in the
      balloon aortic valvuloplasty group, 11.1%. There was one late death in the
      transventricular dilation group. Four patients from the transventricular dilation
      group (19%) and two patients from the balloon aortic valvuloplasty group (22%)
      required reintervention for further relief of aortic stenosis. We conclude that
      both transventricular dilation and balloon aortic valvuloplasty provide adequate
      and equivalent relief of critical aortic stenosis. The treatment strategy adopted
      should depend on other factors, including associated cardiovascular anomalies,
      vascular access, preoperative condition, and the technical expertise available at
      each institution.

PMID- 7815792
TI  - Long-term follow-up of extended aortoplasty for supravalvular aortic stenosis.
AB  - Extended aortoplasty is an operation that was designed to provide a symmetric
      reconstruction of the aortic root in patients with supravalvular aortic stenosis.
      The aim of this report is to provide long-term follow-up of the original cohort
      of 15 patients who underwent extended aortoplasty between 1975 and 1983. Follow
      up was obtained in 14 patients. One patient was lost to follow-up 3 years after
      operation; he was included in this report. An echocardiogram, chest radiograph,
      and electrocardiogram were obtained for each surviving patient. The median length
      of follow-up was 141 months (range 36 to 238). The median preoperative gradient
      was 90 mm Hg (range 55 to 150). The median immediate postoperative gradient was
      20 mm Hg (range 0 to 50, p < 0.05 compared with preoperative gradient) and the
      median long-term gradient was 32 mm Hg (range 6 to 96, p < 0.05 compared with
      preoperative gradient; p = not significant compared with immediate postoperative
      gradient). Two patients died: one of left ventricular failure after a subsequent
      aortic valve replacement and one of chronic left ventricular failure. The Kaplan
      Meier estimate of survival at 218 months for all patients was 77.4% (70%
      confidence limits 62% to 93%). The estimated freedom from reoperation for all
      patients was 69% at 218 months (70% confidence limits 56% to 82%). Univariate
      analysis revealed that the presence of a bicuspid valve is a significant risk
      factor for reoperation (p = 0.038), but not for death (p = 0.51). The Kaplan
      Meier estimate of freedom from reoperation for patients with a bicuspid aortic
      valve was 42.9% at 141 months (70% confidence limits 21% to 65%). Extended
      aortoplasty provides effective long-term relief of the pressure gradient across
      the supravalvular ridge. However, a significant number of patients require
      subsequent operations, particularly those with a bicuspid aortic valve.

PMID- 7815793
TI  - Surgery for congenital mitral valve disease in the first year of life.
AB  - Between 1980 and 1993, 20 patients less than 1 year of age underwent operations
      for congenital mitral valve disease. Ten patients had congenital mitral
      incompetence and 10 had congenital mitral stenosis. Mean age was 6.6 +/- 3.4
      months and mean weight was 5.6 +/- 1.5 kg. Atrioventricular canal defects,
      univentricular heart, class III/IV hypoplastic left heart syndrome, discordant
      atrioventricular and ventriculoarterial connections, and acquired mitral valve
      disease were excluded. Indications for operation were intractable heart failure
      or severe pulmonary hypertension, or both. Associated lesions, present in 90% of
      the patients, had been corrected by a previous operation in seven. In congenital
      mitral incompetence there was normal leaflet motion (n = 3), leaflet prolapse (n
      = 2), and restricted leaflet motion (n = 5). In congenital mitral stenosis
      anatomic abnormalities were parachute mitral valve (n = 4), typical mitral
      stenosis (n = 3), hammock mitral valve (n = 2), and supramitral ring (n = 1).
      Mitral valve repair was initially performed in 19 patients and valve replacement
      in one with hammock valve. Concurrent repair of associated lesions was performed
      in 12 patients. The operative mortality rate was zero. There were six early
      reoperations in five patients for mitral valve replacement (n = 4), a second
      repair (n = 1), and prosthetic valve thrombectomy (n = 1). One late death
      occurred 9 months after valve replacement. Late reoperations for mitral valve
      replacement (n = 2), aortic valve replacement (n = 1), mitral valve repair (n =
      2), subaortic stenosis resection (n = 1), and second mitral valve replacement (n
      = 1) were performed in five patients. Actuarial freedom from reoperation is 58.0%
      +/- 11.3% (70% confidence limits 46.9% to 68.9%) at 7 years. After a mean follow
      up of 67.6 +/- 42.8 months, 94% of living patients are in New York Heart
      Association class I. Doppler echocardiographic studies among the 13 patients with
      a native mitral valve show mitral incompetence of greater than moderate degree in
      one patient and no significant residual mitral stenosis. Overall, six patients
      have mitral prosthetic valves with a mean transprosthetic gradient of 6.2 +/- 3.7
      mm Hg. These results show that surgical treatment for congenital mitral valve
      disease in the first year of life can be performed with low mortality. Valve
      repair is a realistic goal in about 70% of patients and possibly more with
      increased experience. Reoperation rate is still high and is related to complexity
      of mitral lesions and associated anomalies, but late functional results are
      encouraging.

PMID- 7815794
TI  - Use of an intraluminal shunt to repair a coronary bypass graft injury during
      resternotomy.

PMID- 7815795
TI  - Intrahepatic steal after Fontan operation with partial hepatic exclusion.

PMID- 7815796
TI  - Primary cutaneous Nocardia farcinica infection after heart transplantation: a
      case report.

PMID- 7815797
TI  - Myasthenia gravis complicated by sarcoidosis.

PMID- 7815798
TI  - Mediastinal vagal neurilemmoma causing tracheal stenosis.

PMID- 7815799
TI  - Cardiac cannulation, sodium and water balance, and ANF plasma levels.

PMID- 7815800
TI  - Carbon dioxide displacement of left heart chambers.

PMID- 7815801
TI  - Classification of variant courses of the posterior descending artery.

PMID- 7815802
TI  - Dynamic cardiomyoplasty at 5 1/2 years: Russian clinical experience.

PMID- 7815803
TI  - Atherosclerotic changes in the internal thoracic artery.

PMID- 7815804
TI  - Imaging of traumatic rupture of the aorta.

PMID- 7815805
TI  - The use of methylene blue as an extravascular surgical marker impairs vascular
      responses of human saphenous veins.
AB  - Methylene blue is occasionally applied to the adventitia of blood vessels during
      coronary artery bypass and other vascular procedures to assist in the orientation
      of the vessel. Inherent in this method is the assumption that extravascular
      application of methylene blue is innocuous with regard to vascular function. In
      the first part of this study, the in vitro vascular reactivity of methylene blue
      labeled saphenous veins was compared with that of veins that were not marked with
      methylene blue. The vasoactive agents tested were designed to examine multiple
      pathways. They included potassium chloride, prostaglandin F2 alpha,
      phenylephrine, serotonin, angiotensin II, BHT-933 (alpha 2-adrenergic agonist),
      sodium nitroprusside, acetylcholine, isoproterenol, and verapamil. Compared with
      unmarked veins, those marked with methylene blue demonstrated a significant
      impairment of both vasoconstrictor and vasodilator function. These observations
      were made on a relatively small number of patients and could therefore be
      attributed to inherent differences between patients or surgical procedures. In
      the second part of this study, these variables were eliminated by dividing a
      single vein from one patient into three segments for a 45-minute exposure to
      external only methylene blue, internal and external methylene blue, or no
      methylene blue. The segments were then evaluated for vasoreactivity in vitro.
      Externally applied methylene blue reduced vasoconstriction regardless of the
      agonist. Further, both endothelium-dependent and -independent vasodilation was
      diminished by external methylene blue exposure. In veins exposed to methylene
      blue both internally and externally the results were similar but the magnitude of
      impairment greater. It is concluded that surgical marking of blood vessels with
      methylene blue has the potential to adversely affect vascular reactivity and
      therefore the use of alternative dyes should be considered.

PMID- 7815806
TI  - Reoperation on prosthetic heart values. Patient-specific estimates of in-hospital
      events.
AB  - Reoperation on prosthetic heart valves is increasingly under consideration for
      both clinical and prophylactic indications. To determine the correlates of
      hospital events, including in-hospital mortality, new persisting neurologic
      deficit, and length of postoperative stay, a three-institution study of 2246
      consecutive prosthetic valve reoperations performed on 1984 patients between 1963
      and 1992 was undertaken. The combined experience ranged from high-risk patients
      coming moribund to the operating room to an important number of well individuals
      undergoing prophylactic reoperations on potentially failing valves. The risk
      unadjusted hospital mortality was 10.8%, neurologic deficit at hospital discharge
      1.1%, and length of stay 10 days (median). Multivariably determined correlates of
      outcome included age at reoperation, degree, severity, and acuity of impairment
      of cardiac function, extensiveness of valvular heart disease, coexisting morbid
      conditions, number of previous heart operations, and concomitant procedures. The
      risk-adjusted hospital mortality for the first elective reoperation in a good
      risk patient was 1.3% (90% confidence limits 0.3% to 4.4%), neurologic deficit
      0.3% (90% confidence limits 0.02% to 1.8%), and length of postoperative stay 7
      days (90% confidence limits 4 to 13), emphasizing the wide variance in outcome
      events. Equations were developed to permit wide application of the results of the
      study for quantitatively estimating the risk of outcome events based on
      individual preoperative patient characteristics. These estimates should be useful
      for informed patient consent, considerations of prophylactic valve replacement,
      and cost and resource use.

PMID- 7815807
TI  - Analysis of time-dependent risks for infection, rejection, and death after
      pulmonary transplantation.
AB  - Infection and rejection remain the greatest threats to the survival of pulmonary
      allograft recipients. Furthermore, a relationship may exist between these events,
      because the occurrence of one may predispose to the other. By using multivariate
      analysis for repeated events, we analyzed the risk factors for bacterial, fungal,
      and viral infection, grade II or greater acute rejection, and death among 239
      lung transplant recipients who received 250 allografts between January 1988 and
      September 1993. A total of 90 deaths, 491 episodes of acute rejection, and 542
      infectious episodes occurred during a follow-up of 6 to 71 months. The hazard or
      risk patterns of death, infection, and rejection each followed an extremely high
      risk during the first 100 days after transplantation, a second modest risk period
      at 800 to 1200 days, and a lower constant risk. Infection and graft failure
      manifested by diffuse alveolar damage were the major causes of early death (< 100
      days), whereas infection and chronic rejection were primary causes of later death
      after pulmonary transplantation. By multivariate analysis, cytomegalovirus
      mismatching risk for primary infection was the most significant risk factor for
      death, rejection, and infection. Absence of cytomegalovirus prophylaxis was also
      a risk factor for early and late death and late infection. Survival of recipients
      who received cytomegalovirus prophylaxis was significantly improved.
      Immunosuppression based on cyclosporine versus FK 506 was a risk factor for late
      death and late infection. Graft failure manifested by diffuse alveolar
      damage/adult respiratory distress syndrome was a significant risk for death late
      after transplantation. These data suggest the following: (1) The hazard for
      death, infection, and rejection after pulmonary transplantation appears biphasic;
      (2) lower survival is associated with ischemia-reperfusion lung injury
      represented by diffuse alveolar damage/adult respiratory distress syndrome; (3)
      cytomegalovirus mismatch, absence of cytomegalovirus prophylaxis, and development
      of cytomegalovirus disease are significant threats for death, rejection, and
      infection after pulmonary transplantation; (4) prevention of cytomegalovirus
      disease should improve survival by decreasing the prevalence of infection and
      rejection.

PMID- 7815808
TI  - Critical issues in pediatric lung transplantation.
AB  - Forty children (aged 1 to 18 years, 27 female and 13 male) have undergone heart
      lung (21), double lung (17), and single lung (2) transplant procedures at our
      center from 1985 through April 1994. The indications for transplantation have
      been diverse, primary pulmonary hypertension (10), cystic fibrosis (11),
      congenital heart disease (10), arteriovenous malformation (3), emphysema (1),
      graft-versus-host disease (1), rheumatoid lung (1), cardiomyopathy (1),
      desquamative interstitial pneumonitis (1), and Proteus syndrome (1). The
      actuarial 1-year survival was 73% (mean follow-up 2 years). One-year actuarial
      survival for disease groups ranged from 60% for cystic fibrosis to 90% for
      congenital heart disease. We have identified six issues critical to the patient
      and programatic survival of pediatric lung transplantation. Our experience and
      management strategies in these areas are reviewed. Cytomegalovirus:
      Cytomegalovirus disease developed in six of eight patients with cytomegalovirus
      mismatching (donor +/recipient-) and in seven of 32 patients who survived more
      than 30 days (23%). All but cytomegalovirus donor -/recipient- patients were
      treated with ganciclovir for 4 weeks after transplantation. Obliterative
      bronchiolitis: Obliterative bronchiolitis developed in seven of 32 (25%) patients
      who survived more than 30 days. Obliterative bronchiolitis was manifest within
      the first posttransplantation year as a rapid decline in small airway function.
      Aggressive augmentation of immunosuppression has been used with little success.
      Posttransplantation lymphoproliferative disease: Posttransplantation
      lymphoproliferative disease developed in five of 32 (15%) patients who survived
      more than 30 days developed. One patient died (17% mortality) despite
      retransplantation. In four patients the disease resolved with reduction in
      immunosuppression alone, and one required the addition of interferon alfa. Cystic
      fibrosis: We have changed our management strategies to avoid triple drug
      immunosuppression, perioperative blood and bronchial cultures, aggressive
      antimicrobial therapy, and exclusion of patients with panresistant organisms;
      this has resulted in elimination of infectious mortalities thus far in the
      pediatric cystic fibrosis group. Airways: In 21 heart-lung recipients with
      tracheal anastomoses we have had no airway complications. The double and single
      lung transplant recipients accounted for 34 bronchial and one tracheal
      anastomoses. Three (9%) bronchial stenoses developed. Two were treated with
      silicone stents and one with balloon dilation.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7815809
TI  - Endothelial cell-lined skeletal muscle ventricles in circulation.
AB  - Skeletal muscle ventricles were constructed from the latissimus dorsi in six dogs
      by wrapping the muscle around a polypropylene mandrel. Jugular vein endothelial
      cells were harvested enzymatically and grown in tissue culture. After 3 weeks of
      vascular delay and 4 weeks of electrical conditioning, five skeletal muscle
      ventricles were seeded with 5 to 8 x 10(6) autologous endothelial cells by
      percutaneous injection of a cellular suspension into the lumen of the skeletal
      muscle ventricle; one skeletal muscle ventricle was injected with culture medium
      alone as an unseeded control. The autologous endothelial cells were all
      prelabeled with a lipid-bound cellular marker, PKH-26. After an additional 4
      weeks of electrical conditioning, the mandrels were removed and the skeletal
      muscle ventricles were connected to the descending thoracic aorta and activated
      to contract during cardiac diastole at a 1:2 ratio with the heart. After 3 hours
      of continuous pumping, mean diastolic pressure was increased by 35% (58 +/- 7
      versus 78 +/- 6 mm Hg, p < 0.05). At this time, the skeletal muscle ventricles
      were excised for histologic examination. Sections stained with hematoxylin and
      eosin revealed a continuous cellular layer lining the skeletal muscle ventricle;
      no cells were present on the lumen of the control skeletal muscle ventricle. All
      seeded skeletal muscle ventricles exhibited fluorescence as a result of the PKH
      26 cellular marker. Immunofluorescent staining with antibodies to von Willebrand
      factor and ultrastructural analysis with an electron microscope confirmed the
      endothelial character of these cells lining the lumen of the skeletal muscle
      ventricles. The ability to create endothelial cell-lined muscular pumping
      chambers holds important implications for the resolution of thrombotic events in
      cardiac assist devices as well as toward the clinical application of skeletal
      muscle ventricles.

PMID- 7815810
TI  - Experience with the Novacor left ventricular assist system as a bridge to cardiac
      transplantation, including the new wearable system.
AB  - The three components of the Novacor left ventricular assist system, compact
      controller, battery, and back-up battery, have been miniaturized in the
      development of the wearable system. Therefore patients can be fully mobilized
      receiving mechanical circulatory support while awaiting heart transplantation.
      Between February 1992 and April 1994 a total of eight patients with decompensated
      heart failure (6 dilated cardiomyopathy, 1 acute myocarditis, 1 ischemic
      cardiomyopathy) were treated with the Novacor left ventricular assist systems. In
      the most recent four cases the wearable system (N100P) was used. Patients' ages
      ranged from 17 to 49 years. In five patients severe failure of the right side of
      the heart was present at the time of implantation. Hemodynamic stabilization was
      achieved in all patients during the 2 to 122 days (mean 30.8 +/- 42.5 days) of
      support. The following parameters were measured on average before and 24 hours
      after implantation of the left ventricular assist system: mean arterial pressure
      70 +/- 11 versus 87 +/- 13 mm Hg (p < 0.05), cardiac index 1.71 +/- 0.42 versus
      3.23 +/- 0.74 L/min/m2 (p < 0.05), pulmonary capillary wedge pressure 27.1 +/-
      4.4 versus 9.9 +/- 5.2 mm Hg (p < 0.01), mean pulmonary pressure 41 +/- 9 versus
      27 +/- 6 mm Hg (p < 0.05), and right ventricular ejection fraction 16.7% +/-
      10.3% versus 22.0% +/- 11.6% (not significant). Patients who received the
      wearable system were capable of managing their own power supply during the
      bridging period and were able to walk to the hospital park and shopping area. One
      patient had a serious pulmonary infection, which was treated successfully, and
      two patients had a cerebrovascular accident, which resolved in one and resulted
      in a minor residual deficit in the other. All eight patients received a heart
      transplant. One patient died early after transplantation and seven patients are
      alive and well. In summary, the wearable Novacor left ventricular assist system
      provides major advantages regarding quality of life of patients during mechanical
      circulatory support. However, there is a remaining risk of thromboembolism
      despite anticoagulation therapy.

PMID- 7815812
TI  - Endothelium-dependent contraction of canine coronary artery is enhanced by
      crystalloid cardioplegic solution.
AB  - Experiments were designed to determine whether hyperkalemic crystalloid
      cardioplegic solution enhances endothelium-dependent contraction of coronary
      arteries. Segments of canine coronary arteries (n = 8 in each group) were
      preserved in cold (4 degrees C) crystalloid cardioplegic solution (group 1) and
      physiologic solution (group 2) for 60 minutes. Segments of preserved and control
      (group 3) coronary arteries with or without endothelium were suspended in organ
      chambers to measure isometric force. Perfusate hypoxia (oxygen tension 35 +/- 5
      mm Hg) caused endothelium-dependent contraction in the arteries of all three
      groups. However, vascular segments with endothelium of group 1 exhibited hypoxic
      contraction (68.5% +/- 15.3% of the initial tension contracted by prostaglandin
      F2 alpha 2 x 10(-6) mol/L, p < 0.05) that was significantly greater than
      contraction of the group 2 and group 3 segments with endothelium (26.6% +/- 5.6%
      and 20.6 +/- 4.4%). The hypoxic contraction in arteries of group 1 could be
      attenuated by NG-monomethyl-L-arginine, the blocker of endothelial cell synthesis
      of the nitric oxide from L-arginine. The action of NG-monomethyl-L-arginine could
      be reversed by L-arginine but not D-arginine. Thus after preservation with
      cardioplegic solution, augmented endothelium-dependent contraction, occurs by L
      arginine-dependent pathway, would favor coronary vasospasm after cardiac
      operation.

PMID- 7815811
TI  - Coronary vasoconstriction mediated by endothelin-1 in neonates. Reversal by
      nitroglycerin.
AB  - To determine the role of the vasoconstrictor peptide endothelin-1 in
      cardiopulmonary bypass in neonates, we measured plasma endothelin-1
      concentrations in infants before and after cardiopulmonary bypass for arterial
      switch procedures and studied the effects of endothelin-1 on coronary tone and
      contractility in normal and reperfused neonatal pig hearts. Endothelin-1 blood
      concentrations (picograms per milliliter, mean +/- standard error) were
      significantly higher in neonates with arterial transposition and in umbilical
      venous blood (22.9 +/- 2.3 and 19.2 +/- 2.9, respectively) than in older children
      with atrial septal defects (13.2 +/- 1.6) or in healthy adults (10.7 +/- 2.5).
      After cardiopulmonary bypass, endothelin-1 concentrations increased 29% in
      neonates undergoing arterial switch procedure and 28% in children undergoing
      atrial septal defect repair (p < 0.05 versus before bypass). In isolated, blood
      perfused neonatal pig hearts, endothelin-1 had dose-related coronary constrictor
      and inotropic effects between 25 and 100 pmol. Endothelin-1 concentrations that
      did not increase coronary perfusion pressure (5 to 10 pmol) caused significant
      coronary constriction in the presence of norepinephrine (10 nmol/L). During
      reperfusion after 30 minutes of global normothermic ischemia, the coronary
      vasoconstrictor effects of both endothelin-1 alone and endothelin-1 plus
      norepinephrine were significantly enhanced. Nitroglycerin reversed
      vasoconstriction produced by endothelin-1 and endothelin-1 plus norepinephrine
      both before and after ischemia-reperfusion. We conclude that endothelin-1
      concentrations are significantly elevated in neonates and are further increased
      after cardiopulmonary bypass. Coronary vasoconstriction caused by endothelin-1 is
      enhanced by ischemia-reperfusion and by norepinephrine present in concentrations
      typically observed after neonatal cardiopulmonary bypass. Nitroglycerin reverses
      coronary vasoconstriction induced by endothelin-1 and may therefore be beneficial
      in the postoperative management of neonates after cardiac operations.

PMID- 7815813
TI  - A new triple-channel swivel for fluid delivery in the range of intracranial (10
      nl) and intravenous (100 microliters) self-administration volumes and also
      suitable for microdialysis.
AB  - This paper describes a new low-torque, bubble-free and multiple-channel swivel of
      easy construction. This swivel combined with the use of fused silica capillary
      tubing to connect syringes and injectors, as we recently proposed, allow the
      accurate and repeated microinjection of low nanoliter volumes (10 nl) in freely
      moving rats, as required in the intracranial self-administration paradigm.
      Microinjections can be simultaneously performed in 3 different brain regions.
      Relatively large volumes in the 10-100 microliters range can be repeatedly
      administered, as in intravenous self-administration, using the traditional
      connections with polyethylene (PE) tubing. This swivel allows the execution of
      experiments involving in vivo microdialysis in up to 3 different brain areas. The
      internal channel has a very low dead space (4 microliters) and can be used to
      withdraw small liquid samples and perform on-line microdialysis in freely moving
      animals. This versatility makes the present swivel appropriate for sophisticated
      experimental designs involving combinations of intracranial, intravenous and/or
      intragastric self-administration with microdialysis.

PMID- 7815814
TI  - A simple and rapid method for sequencing the entire coding region of the human
      prion protein (PrP) gene.
AB  - The accumulation in brain of the 'prion protein' (PrP), a host-encoded
      sialoglycoprotein, is the unique specific molecular marker of subacute spongiform
      transmissible encephalopathies (SSTE). Furthermore, the primary sequence of the
      PrP gene (PRNP) seems to contain some genetic determinants of great importance in
      the development of SSTE. Here we present a simple and rapid polymerase chain
      reaction (PCR)-based method for direct sequencing of the entire coding sequence
      of the PrP gene, PRNP, in patients. The ability to determine sequences of both
      alleles of the PRNP gene is demonstrated in the analysis of 3 patients previously
      established as codon 129 heterozygotes by the use allele-specific oligonucleotide
      hybridization method.

PMID- 7815815
TI  - A system for quantitative analysis of associative learning. Part 1. Hardware
      interfaces with cross-species applications.
AB  - This paper describes a reliable, durable, and readily calibrated hardware
      interface system designed to present sensory stimuli at precise time intervals
      and to transduce and digitize behavioral data in classical conditioning
      experiments. It has been extensively tested in a 'model'-associative learning
      task, conditioning of eyeblink or nictitating membrane responses, but is readily
      adapted to other behavioral paradigms. Each system can run a pair of conditioned
      experimental or pseudoconditioned control subjects simultaneously, or collect
      data from a single subject carrying out two tasks simultaneously. The
      requirements of the system are defined, based around an inexpensive AT-class MS
      DOS microcomputer. The interface hardware needed to present auditory tone
      conditioned stimuli and corneal airpuff-unconditioned stimuli to training
      subjects are detailed, with timing signals provided by TTL pulses generated at
      the digital output ports of an analog-to-digital (A/D) converter. An electronic
      circuit is described that provides stable inputs to the A/D converter,
      transducing eyeblink responses to voltage signals opto-electronically, without
      requiring any invasive attachment of the subject to the subject to the measuring
      device. The 1-piece eyeblink sensor used (selected for ease of alignment and
      maintenance) is also discussed. Examples of applications for classical
      conditioning of rabbits, rats, and human subjects are described. A companion
      paper describes data-acquisition and control software written as a user-friendly
      interface for this hardware system.

PMID- 7815816
TI  - A system for quantitative analysis of associative learning. Part 2. Real-time
      software for MS-DOS microcomputers.
AB  - Microcomputer software was designed and used to control the timing and delivery
      of sensory stimuli and to acquire and analyze behavioral data during classical
      conditioning experiments. The software package runs under DOS 4.x through 6.x
      (earlier versions run under DOS 3.x) on PC AT-compatible microcomputers coupled
      with appropriate interface hardware (see Thompson et al., 1994). The software
      controls timed delivery of up to 8 conditional stimuli. It can collect behavioral
      data from 2 subjects simultaneously performing the same task (e.g., eyeblink
      responses) or from a single subject performing 2 different tasks (e.g., both
      eyeblink and conditional discrimination tasks), permitting its use in a number of
      experimental paradigms. Digital timing signals are adjustable for different
      stimulus output systems. Behavior is continuously monitored onscreen, ensuring
      consistent measurement across trials. Real-time performance measures of the
      presence or absence of conditioned responses allow coordination with external
      events (e.g., serum sampling, drug delivery, or single-unit recording).
      Quantitative measures are generated both for each trial and for complete
      sessions. Records are stored to disk and can be printed or merged for statistical
      analyses. Data can be archived on standard media, and internal software utilities
      translate files for export to PC and Macintosh programs. This system and the
      hardware described in the preceding paper combine ease of use with extremely
      replicable behavioral measurements across trials, sessions subjects, cohorts, and
      studies.

PMID- 7815817
TI  - A method for the quantification of synchrony and oscillatory properties of
      neuronal activity.
AB  - Interactions between neurones can be analysed by simultaneously recording from
      several cells and computing correlation functions between the respective
      activities. Recent studies have revealed that neuronal responses are often
      synchronous and exhibit an oscillatory temporal structure. These two properties
      are commonly assessed together from correlation functions. In order to evaluate
      these variables independently a method was devised for the quantification of a
      generalized Gabor function that was fitted to the correlograms. The performance
      of the method was tested on a large data set from cat area 17 and its stability
      was examined with respect to its dependence on the number of free parameters. The
      results demonstrate that the proposed fitting algorithm is robust in that it is
      rather independent of starting conditions and converges to optimal fits even with
      different settings of free variables. The fitted correlation function allow for
      an automatic and independent classification of synchrony on the one hand and
      oscillatory firing patterns on the other.

PMID- 7815818
TI  - A new approach to optical imaging applied to rat barrel cortex.
AB  - Several groups have described using intrinsic optical imaging to form images of
      activity patterns in the cortex. Because the signal is small, the general
      approach has been to use expensive camera equipment with a high dynamic range to
      make these measurements. However, by using signal averaging to compensate for
      lower dynamic range, images can be obtained using equipment already available in
      many laboratories. This modified technique has been used for imaging activity in
      'barrel' cortex of the rat. A map of the representation of a single whisker as
      determined by the imaging technique corresponded well with a similar map made
      using standard electrophysiology. A map of several whiskers was made by
      overlaying images of single-whisker representations. The details of the images
      differ from those previously described. Possible mechanisms for the signal are
      discussed.

PMID- 7815819
TI  - Optimizing the measurement of regional cerebral glucose consumption with [6
      14C]glucose.
AB  - [6-14C]Glucose is used to trace the cerebral metabolic rate of glucose (CMRGlc)
      in vivo in experiments lasting 5-10 min. Initially 14C is trapped in intermediary
      metabolite pools. Subsequently 14C is lost as a function of time and metabolic
      rate, primarily as 14CO2. Experiments were designed to evaluate the rate of 14C
      lost as 14CO2 or as [14C]lactate from brain labeled with [6-14C]glucose during
      times up to 15 min. CMRGlc was measured during 5, 7.5, 10 and 15 min in 60 brain
      areas. At longer times the loss of 14C was reflected by lower apparent values of
      brain CMRGlc. Arteriovenous measurements across brain revealed no significant
      loss of [14C]lactate in normal rats or rats with bicuculline-induced seizures. It
      was concluded that the primary form in which 14C was lost was as 14CO2. As
      expected, the rate of 14CO2 loss was greater in structures with high metabolic
      rates. The data were analyzed to determine the parameters necessary to rectify
      the data so that uniform values of CMRGlc were obtained up to 15 min. Tables were
      made to predict the degree of 14C loss as well as the 14C-metabolites/[6
      14C]glucose ratio as a function of time and metabolic rate. These tables can be
      used to plan the maximum and minimum experimental times for optimal results.

PMID- 7815820
TI  - Long-term survival of dopaminergic neurones in free-floating roller tube cultures
      of human fetal ventral mesencephalon.
AB  - Transplantation of human fetal ventral mesencephalon (VM) to Parkinsonian
      patients has shown beneficial effects in several clinical trials. However,
      further improvements in the transplantation technique are needed. Delayed
      surgery, i.e., the in vitro maintenance of the tissue prior to transplantation
      would present several advantages. The roller tube technique as initially
      described by Gahwiler (1981) was modified in several aspects for the long-term
      maintenance of dopaminergic neurones of human fetal VM. Tissue cultures were
      maintained free-floating in the medium for up to 42 days. The human fetal
      material was obtained from legal induced suction abortions. The embryonic age
      ranged from 5 to 12 weeks post-conception. Identification of VM was possible in
      43% of the cases. Neurones in cultures were demonstrated by means of
      immunohistochemistry for tyrosine hydroxylase (TH) and gamma-amino butyric acid
      (GABA), by electron microscopy and by hybridisation histochemistry using a TH
      mRNA-sensitive probe. A high variability in the number of TH-positive cells in
      individual cultures derived from the same embryo was observed. In 20 microns
      frozen sections of such tissue cultures the mean +/- SEM of TH-positive cells was
      6.5 +/- 1.2/0.1 mm2 (n = 79; range: 0-73). The technique described insures the
      growth of long-term cultures of human fetal VM.

PMID- 7815821
TI  - The effect of inhibition of synthesis, release, metabolism and uptake on the
      microdialysis extraction fraction of dopamine.
AB  - The present study was designed to determine the effects that synthesis, release,
      metabolism and uptake have on the in vivo extraction fraction (relative recovery)
      of dopamine (DA) in the nucleus accumbens of the rat. The extraction fraction and
      extracellular concentration of DA were established for rats that were perfused
      with artificial cerebrospinal fluid (aCSF) with or without substances inhibiting
      synthesis (100 microM alpha-methylparatyrosine (alpha-MPT)), release (1 microM
      tetrodotoxin (TTX)), uptake (1 microM, 20 microM cocaine or 1 microM GBR-12909)
      or metabolism (100 microM tropolone or 100 microM pargyline) with DA
      concentrations ranging from 0 to 200 nM. Inhibiting synthesis with alpha-MPT or
      release with TTX had no effect on the extraction fraction of DA. Inhibiting
      intracellular or extracellular metabolism with pargyline or tropolone,
      respectively, did not cause any changes in the extraction fraction. However,
      inhibiting uptake with 20 microM cocaine or 1 microM GBR-12909 decreased the
      extraction fraction by one-third and one-half, respectively. These results
      provide evidence that uptake is the primary neuronal process affecting the
      extraction fraction of DA in the nucleus accumbens and indicate that the
      extraction fraction may be useful as an index of DA uptake in vivo.

PMID- 7815822
TI  - A new cytochemical method for the ultrastructural localization of calcium in the
      central nervous system.
AB  - We have developed a new cytochemical method for the localization of calcium at
      the ultrastructural level in the central nervous system (CNS). The method is
      based on the use of phosphate buffer in the primary fixation followed by a
      mixture of a complex of chromium(III)-trisoxalate and osmium tetroxide (OsO4)
      which precipitates calcium and results in the formation of a high electron-dense
      reaction product. Calcium selectivity was verified by reactions made in test
      tube, by EGTA treatment of the tissue, by electron spectroscopic imaging (ESI)
      and electron energy loss spectroscopy (EELS). The technique was found to be
      reproducible, yielding similar results in acutely prepared hippocampal slices or
      organotypic cultures fixed by immersion and in brain areas fixed by perfusion. In
      hippocampal slices, calcium deposits were found to accumulate in different
      subcellular compartments such as endoplasmic reticulum, mitochondria and synaptic
      vesicles. Interestingly, electron-dense reaction products were also visualized in
      smooth endoplasmic reticulum structures localized in presynaptic terminals or
      post-synaptic spines as well as in synaptic clefts and active zones. This new
      method may thus be of interest for studying the metabolism of calcium,
      specifically with regard to synaptic activity, in the CNS.

PMID- 7815823
TI  - A neural network-based spike discriminator.
AB  - A software routine to reconstruct individual spike trains from multi-neuron,
      single-channel extracellular recordings was designed. Using a neural network
      algorithm that automatically clusters and sorts the spikes, the only user input
      needed is the threshold level for spike detection and the number of unit types
      present in the recording. Adaptive features are included in the algorithm to
      allow for tracking of spike trains during periods of amplitude variation and also
      to identify noise spikes. The routine will operate on-line during extracellular
      studies of the cochlear nucleus in cats.

PMID- 7815824
TI  - An improved procedure for the immunohistochemical localization of nerve growth
      factor-like immunoreactivity.
AB  - Nerve growth factor (NGF) is a survival factor required by a number of neuronal
      populations including most post-ganglionic sympathetic neurones. NGF has been
      detected and quantified in many tissues but there is little information regarding
      its cellular localization. Although it has been argued that histological
      detection has proven difficult due to the low levels of NGF present, other
      factors may contribute to prevent its identification. In the present study, we
      report a method for the histological detection of NGF-like immunoreactivity in
      the rat superior cervical ganglia (SCG). Adult Wistar-Kyoto rats were perfused
      briefly with either a high or low pH buffer prior to fixation and routine
      immunohistochemistry. Polyclonal antibodies to native mouse NGF used in the
      present study recognized mouse NGF but not recombinant human neurotrophin 3
      (rhNT3) or brain-derived neurotrophic factor (rhBDNF) by immunoblot analysis. NGF
      like immunoreactivity was localized to most sympathetic neurones.
      Immunoreactivity was detected in the cytoplasm with dense labelling around
      nuclei. No stain was seen in sections incubated with normal sheep IgG or from
      animals perfused with phosphate buffer (pH 7.4) prior to fixation. In addition,
      axotomy resulted in the disappearance of NGF immunoreactivity which was confirmed
      by biochemical quantification. Finally, no NGF immunoreactivity was found in
      neurones of rats treated systemically with NGF antiserum 3 days earlier. Possible
      mechanisms underlying the improvement of NGF immunohistochemistry by pH
      manipulation before fixation are discussed.

PMID- 7815826
TI  - In vitro study of human alveolar macrophage and peripheral blood mononuclear cell
      reactive oxygen-intermediates release induced by sulfur dioxide at different
      concentrations.
AB  - Sulfur dioxide (SO2) is a major air pollutant in urban areas. Alveolar
      macrophages (AM) located on the alveolar surface are in direct contact with this
      inhaled gas. We evaluated the dose-dependent effect of SO2 exposure on the
      oxidative metabolism of AM and peripheral blood mononuclear cells (PBMNC) by
      measuring the spontaneous and stimulated reactive oxygen intermediates (ROI)
      release. AM or PBMNC were placed on a polycarbonate membrane, which was in direct
      contact with the surface of a nutrient reservoir. For exposure of the cells to
      SO2 a special chamber was employed, in which humidified standard air with 5% CO2
      at 37 degrees C was mixed with SO2 at the desired concentration. Periods of time
      between 30 and 120 minutes and concentrations between 0.3 and 1.5 ppm SO2 were
      chosen for exposure. Thirty minutes exposure of AM to SO2 (0.3-1.5 ppm) yielded a
      dose-dependent stimulation of ROI release; 2.0- to 3.6-fold of control (r =
      0.965, p < 0.005). An exposure of 120 minutes to SO2 resulted in a similar ROI
      production of about 2.5-fold at all tested concentrations. These experiments
      provide evidence that AM and PBMNC become activated by SO2 producing large
      amounts of ROI.

PMID- 7815827
TI  - Immunogenetic studies on HLA-DR in German coal miners with and without coal
      worker's pneumoconiosis.
AB  - Coal worker's pneumoconiosis is caused by the pulmonary deposition of coal dust,
      including silica particles. Several factors such as chemical composition and
      physical properties of silica-containing dust, particle size distribution,
      intensity, and duration of exposure influence the disease development. Genetic
      factors may also be involved. To define whether HLA-DRB may function as a genetic
      factor for predisposition to coal worker's pneumoconiosis, we determined DRB1, 3,
      4, 5 alleles. For this purpose, DRB typing with sequence-specific oligonucleotide
      probes in 204 German miners with pneumoconiosis and in 52 German miners without
      pneumoconiosis was used. The miners had worked under comparable conditions. The
      frequency of DR8 (1*0801-0804) was increased in patients developing
      pneumoconiosis during the first 15 years of mining (p = 0.047). The frequency of
      DR1 (1*0101-0103) was elevated (p = 0.022) and that of DR52 (3*0101, 3*0201,
      3*0202, and 3*0301) was reduced (p = 0.026) in miners without pneumoconiosis. Our
      data show that the presence of DR1 and the absence of DR52 support the resistance
      to coal worker's pneumoconiosis. Furthermore, DR8 may be involved in the rapid
      development of coal worker's pneumoconiosis.

PMID- 7815828
TI  - Stimulation of GTP hydrolysis in guinea pig bronchial membranes by mastoparan.
AB  - Guanine nucleotide-binding proteins, or G proteins, play an important role in
      transmitting information from membrane receptors to intracellular effector
      systems. Activation of G proteins results in the hydrolysis of GTP, and the
      measurement of GTPase activity represents a means by which the role of G proteins
      in signal transduction can be investigated. GTPase activity of guinea pig
      bronchial membranes was measured as the liberation of 32Pi from [gamma-32P]GTP.
      GTPase activity was divided into two components, one possessing a high affinity
      and the other a low affinity for GTP. The contribution of high- and low-affinity
      GTPase to total hydrolysis was dependent on Mg2+. In the presence of
      submicromolar Mg2+, high-affinity GTPase represented 65-80% of all activity,
      whereas in the presence of > or = 26 microM Mg2+, all detectable hydrolysis was
      due to the low-affinity GTPase. High-affinity GTPase was stimulated by Mg2+ in
      the 0.15-1.1 microM range (2.5-fold maximal stimulation, apparent Km for Mg2+
      0.31 microM). Mastoparan (1-100 microM) caused a concentration-dependent
      stimulation of high-affinity (but not low-affinity) GTPase (71 +/- 13% maximal
      stimulation, EC50 0.38 microM), suggesting that high-affinity GTPase may be due
      to a G protein. Carbachol (10 microM) and fenoterol (10 microM) had no effect on
      high-affinity GTP hydrolysis, suggesting that under the conditions described,
      GTPase activity of bronchial membranes is not activated by muscarinic or beta
      adrenergic receptors, respectively.

PMID- 7815829
TI  - History of promyelocytic leukaemia.
AB  - The first reports on promyelocytic leukaemia came from Norway and France in 1957.
      Little by little, acute promyelocytic leukaemia acquired its rightful place in
      nosology as a hyperacute, invariable and rapidly fatal disease. In 1973, a high
      frequency of complete remissions induced by strong doses of daunorubicin and an
      acceptable frequency of true recovery, was demonstrated. After these preliminary
      events, the history of promyelocytic leukaemia was that of an important
      discovery: the first remissions of human acute leukaemia were obtained by cell
      differentiation, as all-trans retinoic acid induces complete remission of acute
      promyelocytic leukaemia in nearly all cases. The consequences of the discovery
      are discussed. For the long or middle term, we can hope for improved
      understanding of the action of retinoic acid, and possibly the preparation of new
      compounds with longer efficiency.

PMID- 7815825
TI  - Cellular and immunological markers of allergic and intrinsic bronchial asthma.
AB  - Based on a growing body of evidence, allergic as well as intrinsic bronchial
      asthma have recently been defined as chronic persistent inflammatory disorders.
      Agreement has been reached that asthma can no longer be equated with bronchospasm
      only, and that the absence of reversibility of airflow obstruction does not
      exclude bronchial asthma. Bronchial hyperreactivity, on the other hand, although
      common to the vast majority of asthmatics, is not specific for bronchial asthma
      and provocation tests to measure bronchial hyperreactivity are not suited for
      routine monitoring of bronchial asthma. The clinical features of asthma are
      related to cellular as well as to soluble parameters of bronchial inflammation.
      Therefore, means of assessing and monitoring asthmatic inflammation have been
      investigated. Since eosinophils, T lymphocytes, mast cells, macrophages,
      neutrophils, epithelial cells, and structural cells, as well as various
      proinflammatory mediators and proteins, have been implicated in the pathogenesis
      of bronchial asthma, it has been anticipated that several of these cells or
      mediators might be either diagnostic of bronchial asthma or could serve as
      markers to monitor the underlying bronchial inflammation. Currently there is no
      diagnostic marker of bronchial asthma, which, on its own, either confirms or
      excludes bronchial asthma with appropriate sensitivity and specificity.
      Clinically the most reliable feature of bronchial asthma that seems to be related
      closely to the symptomatology still is the presence of eosinophils in peripheral
      blood, and especially in sputum. Eosinophil-derived products, particularly
      eosinophil granule proteins, have been investigated as markers of eosinophil
      participation in the pathogenesis of asthma and, comparable to eosinophil numbers
      themselves, are possible predictors of impending exacerbations of allergic, as
      well as intrinsic bronchial asthma. However, clinically their precise value in
      diagnosing and monitoring of bronchial asthma has not been documented
      convincingly and requires further investigation. Increasing data suggest that the
      regulation of eosinophilia is largely conveyed by interleukin-5 (IL-5) released
      from activated T-helper lymphocytes and possibly other cells. Therefore, T
      lymphocyte activation, and especially assessment of systemic and local IL-5
      levels, might be of diagnostic value and possibly useful in monitoring of
      inflammation in bronchial asthma in the future. A possible role and future
      applications for other markers of inflammation not related to eosinophils in
      monitoring or diagnosing bronchial asthma need to be established.

PMID- 7815830
TI  - Acute Promyelocytic Leukemia: A Curable Disease? Symposium proceedings. Rome,
      Italy, November 11-12, 1993.

PMID- 7815831
TI  - In vitro all-trans retinoic acid (ATRA) sensitivity and cellular retinoic acid
      binding protein (CRABP) levels in relapse leukemic cells after remission
      induction by ATRA in acute promyelocytic leukemia.
AB  - The current treatment of acute promyelocytic leukemia (APL, also called AML3
      subtype) is focused on differentiating agents such as the vitamin A derivative
      all-trans retinoic acid (ATRA). This agent is a novel and very promising therapy
      for this disease characterized cytogenetically by a translocation
      t(15;17)(q21;q22) involving the alpha retinoic acid receptor on chromosome 17 and
      the PML gene on chromosome 15. Clinical trials have demonstrated that ATRA
      followed by or combined with conventional chemotherapy may be more beneficial
      than chemotherapy for inducing complete remission. Unfortunately, ATRA as a
      single agent, does not appear able to maintain patients in remission (median 5
      months), and when relapse occurs resistance to a second induction of ATRA therapy
      is observed in almost all cases. Recently our laboratory investigated whether
      specific features of the AML3 cells at relapse could explain the in vivo
      resistance observed. We have demonstrated that AML3 patients' cells (from four
      patients) at relapse show high levels of CRABP, a cytosolic retinoic acid binding
      protein and this protein was not detected prior to ATRA therapy. Relapse-AML3
      cells (n = 12) showed reduced differentiation induction when compared with
      'virgin'-AML3 cells. Results from this study suggest that CRABP could modulate
      ATRA cellular concentrations reaching the nucleus. This induced ATRA
      hypercatabolytic state should be monitored during consolidation therapy and at
      relapse by evaluating CRABP and RA metabolite levels, in order to detect ATRA
      resistance in patients with AML3.

PMID- 7815832
TI  - The pathophysiology and treatment of hemorrhagic syndrome of acute promyelocytic
      leukemia.
AB  - Acute promyelocytic leukemia (APL) has been historically characterized by a high
      rate of early hemorrhagic death, particularly from intracranial bleeding. The
      hemorrhagic complications have been attributed to a combination of intravascular
      thrombin generation, excessive fibrinolysis and/or proteolytic activities
      released from blast cells. Before the era of all-trans retinoic acid (ATRA), the
      incidence of early fatal bleeding in recent series has ranged from 8 to 46%, and
      no anti-hemorrhagic treatment clearly appeared superior in abating this
      complication. This uncertainty is due to remain because of the lack of
      prospective studies. The increasing awareness of the need for prompt diagnosis
      and treatment of APL and the larger availability of supportive therapy has
      largely contributed to lessen the incidence of fatal bleeding, which can be
      reliably estimated around 10% in major centers. Groups pioneering the use of ATRA
      have reported a rapid improvement of the coagulopathy of APL, usually starting 48
      h from the beginning of the treatment. However, the hemostatic changes during
      ATRA have been monitored only in a few patients and recent results suggest that
      hyperfibrinolysis/proteolysis is rapidly corrected by ATRA, whereas thrombin
      generation may persist longer. Moreover, although significantly less frequent,
      fatal bleeding may occur during ATRA and thrombotic events have also been
      reported so that hemostatic death rate is also approximately 10% in patients
      treated with ATRA. The combination of chemotherapy plus ATRA administration
      during induction has been suggested as a useful means of controlling
      hyperleukocytosis, and this could contribute in abating this unacceptably high
      rate of early death. On the other side, chemotherapy can dramatically exacerbate
      clotting abnormalities leading to catastrophic clinical outcomes. Thus, more
      detailed studies of the coagulopathy of APL and its changes during treatment with
      ATRA, or ATRA combined with chemotherapy, are required in order to offer the most
      appropriate treatment to these patients still at risk of severe bleeding and
      thrombotic complications.

PMID- 7815833
TI  - Acute promyelocytic leukemia: morphological aspects.
AB  - Among AML with maturation, acute promyelocytic leukemia (APL) represents a
      distinct subtype which accounts for 5-10% of all the FAB variants. APL may be
      recognized by different cytological pictures: (i) Hypergranular APL, the most
      typical form, showing promyelocytes with cytoplasm packed with purple granules.
      Most of the primary granules may be incorporated into Auer rods, sometimes
      stacked in bundles of faggots. (ii) Microgranular APL, characterized by fine dust
      like granulation in the cytoplasm; some promyelocytes may even appear agranular
      by light microscopy. Most of the cells show bilobed or folded nuclei, a picture
      which may simulate that of acute myelomonocytic leukemia. (iii) Hyperbasophilic
      form, characterized by cells with high N/C ratio, and strongly basophilic
      cytoplasm with either sparse or no granules. Conspicuous cytoplasmatic budding is
      usually present, recalling the feature of micromegakaryocytes. Strong positivity
      for myeloperoxidase, Sudan black B and chloroacetate esterase represents the
      typical cytochemical pattern of M3; usually a weaker reactivity may be observed
      in M3v. However, sometimes a degree of cytochemical heterogeneity of APL cells
      may be observed, as suggested by cases displaying a strong sodium fluoride
      sensitive nonspecific esterase reaction. Recently a distinct entity associated
      with basophilic differentiation has been described. Differential diagnosis of
      this form with M2-baso subtype and with cases of MDS or AML with basophilia (M2,
      M4 with t(6;9) translocation) may be obtained by the use of cytochemistry,
      cytogenetic investigations, and electron microscopy.

PMID- 7815834
TI  - Treatment of acute promyelocytic leukemia with all-trans retinoic acid: an update
      of the New York experience.
AB  - In an ongoing study, we treated 79 patients with a molecular diagnosis of acute
      promyelocytic leukemia (APL) using all-trans retinoic acid (RA) for remission
      induction. Newly diagnosed patients received cytotoxic chemotherapy for
      consolidation, and previously treated patients received extended all-trans RA
      therapy, or a radionuclide-conjugated monoclonal antibody as post-remission
      treatment. Unlike studies in Europe, full-dose chemotherapy was not given during
      induction for patients who developed leukocytosis. Overall, 43 of 49 newly
      diagnosed patients (88%) and 25 of 30 previously treated patients (83%) achieved
      complete remission. We did not encounter de novo resistance to all-trans RA in
      any patient who was positive for PML/RAR-alpha rearrangements by reverse
      transcription polymerase chain reaction analysis. Ten patients died during
      induction from intracranial or pulmonary hemorrhage (six patients) or the
      'retinoic acid syndrome' (four patients). The use of leukapheresis or low-dose
      chemotherapy (hydroxyurea or cytosine arabinoside) for drug-induced leukocytosis
      did not decrease early mortality. Compared to historical controls, early
      mortality was not affected by treatment with all-trans RA; however, both relapse
      free and overall survival were significantly increased. Maintenance therapy with
      all-trans RA was associated with short remission duration, and relapses while
      taking the drug were universally associated with resistance to further retinoid
      treatment. We conclude that the use of all-trans RA for remission induction, with
      or without full-dose chemotherapy, has significantly increased the survival of
      patients with APL. While early mortality has not yet been reduced, the avoidance
      of full-dose chemotherapy during induction has significantly reduced early
      morbidity. The major outstanding clinical issue is the development of strategies
      that maximize safety in high-risk patients for whom intracranial hemorrhage
      remains the major cause of death.

PMID- 7815835
TI  - Treatment outcome with chemotherapy in acute promyelocytic leukemia: the
      Southwest Oncology Group (SWOG) experience.
AB  - Because of interest in new approaches to treatment of patients with acute
      promyelocytic leukemia (APL), we analyzed APL treatment outcome in SWOG with
      chemotherapy from 1982-1991. To evaluate effects of change in nonspecific patient
      care factors over time we evaluated outcome in two temporal groups (1982-1986,
      1986-1991), corresponding to two groups of treatment protocols encompassing all
      new de novo AML patients entered on acute myeloblastic leukemia (AML) protocols
      during those years. Surprisingly, APL patients in the 1982-1986 group (n = 45)
      had much better treatment outcome (complete remission (CR) rate 71%, median
      overall survival (OS) 106 months, median disease-free survival (DFS) > 105
      months) than the later group (n = 96) (CR rate 47%, median OS 13 months, median
      DFS 28 months) (p = 0.0063, 0.0015, and 0.0001 respectively). All APL patients
      but two in the 1982-1986 time period were treated on SWOG protocol 8124, which
      included induction with total daunorubicin (DNR) 210 mg/m2 i.v./course,
      consolidation with two courses with identical dosage of DNR, and intensification
      at 4 months including another course of identical dosage DNR. We analyzed factors
      affecting treatment outcome for all patients with APL treated from 1982 to 1991.
      In multivariate analysis, higher DNR induction dose was significantly associated
      with CR rate, OS, and DFS (p < 0.001, < 0.0001, and < 0.0001, respectively).
      Cytosine arabinoside (ARA-C) dose and inclusion of other agents did not correlate
      significantly with outcome. Because these studies were not randomized for DNR
      dosage, other factors contributing to outcome cannot be completely excluded,
      although none were found. Most deaths occurred within 3 months of initiation of
      therapy on 8124; there were no relapses with higher DNR dosage after 3 years.
      This excellent outcome should be considered in evaluating newer modalities of
      therapy such as all-trans retinoic acid (ATRA) for APL. If the high CR induction
      rate and minimal early deaths with ATRA therapy can be combined successfully with
      this chemotherapy, most patients with APL may be curable.

PMID- 7815836
TI  - Treatment of newly diagnosed acute promyelocytic leukemia (APL) by a combination
      of all-trans retinoic acid (ATRA) and chemotherapy. French APL Group.
AB  - All-trans retinoic acid (ATRA) is very effective in newly diagnosed acute
      promyelocytic leukemia (APL), yielding remission (CR) rates of 80 to 90%.
      However, it is associated with a rapid rise in WBC in some patients, with
      potentially fatal ATRA syndrome. Furthermore, most patients relapse with
      maintenance therapy using ATRA alone or low-dose chemotherapy. The French APL
      group thus designed a treatment approach with ATRA followed by intensive
      chemotherapy. The latter was administered after CR achievement with ATRA, or was
      rapidly added to ATRA in the case of rapid rise in leukocyte counts. This
      combined approach, in a pilot study and in a randomized trial, proved superior to
      intensive chemotherapy alone, by slightly increasing the CR rate but more
      importantly by reducing the relapse rate. The French group (and other European
      groups) are now testing in a new randomized trial the better timing of ATRA and
      chemotherapy administration (ATRA followed by chemotherapy or ATRA plus
      chemotherapy), and the role (after an intensive consolidation) of maintenance
      treatment with intermittent ATRA, continuous low-dose chemotherapy, or both.

PMID- 7815837
TI  - Treatment of patients with acute promyelocytic leukemia. The EORTC-LCG
      experience. EORTC Leukemia Cooperative Group.
AB  - Acute promyelocytic leukemia (M3) is, as one of the FAB subtypes of AML, included
      in the EORTC/GIMEMA AML-8A and 8B randomized trials. In these trials 1519
      patients were included, 477 of them in non-Italian EORTC-LCG centers and 1042 in
      GIMEMA centers. A total of 80 patients were classified as M3 including 18
      patients with M3-variant. Thirty-nine were male and 41 female. Ages ranged from
      15 to 59 years; 25 (31.3%) of them were younger than 30, 34 (42.5%) between 30
      and 45, and 21 (26.3%) older than 45 years of age. 56.3% of the patients had
      leukocytes less than 5 x 10(9)/l at the time of diagnosis vs. 24.9% of the
      patients belonging to the other FAB subtypes. Remission induction consisted of a
      standard protocol with 3 days daunorubicin and 7 days of cytosine arabinoside.
      Forty-three patients (53.8%) achieved a complete remission compared to 64.6% of
      the remaining AML patients. After salvage treatment this percentage increased to
      70%, which is the same as for the other AML subtypes. Thirteen (16.3%) patients
      died during remission induction, mainly due to hemorrhagic complications. This
      percentage is significantly higher than the death rate (9.1%) in the other FAB
      subtypes of AML. All patients received one course of consolidation treatment.
      Post consolidation treatment could be either standard maintenance, intensive
      consolidation courses, autologous or allogeneic transplantation, according to the
      guidelines of the treatment protocols. At present, relapses almost all in the
      bone marrow, are seen in only 34.9% of the M3 patients, compared to 48.4% in the
      remaining AML patients. Disease-free survival for patients less than 45 years of
      age with the M2 and M3 subtypes was approximately 50% at 3 years compared to 30
      40% for the other FAB subtypes. Despite the higher death rate during induction,
      the long-term survival results were better for M3 patients in comparison with the
      remaining AML patients. The projected survival at 3 years was 50% for M3 patients
      vs. 38% for remaining patients.

PMID- 7815838
TI  - The 'standard of care' in acute promyelocytic leukemia.

PMID- 7815839
TI  - Treatment of newly diagnosed APL. The best choice is not ATRA or chemotherapy ...
      but a combination of both. European APL Group.

PMID- 7815840
TI  - Is acute promyelocytic leukemia a curable disease? Treatment strategy for a long
      term survival.
AB  - The major cause of early death in acute promyelocytic leukemia (APL), the high
      risk of a bleeding diathesis is now successfully counteracted within a few days
      by differentiation therapy using ATRA. Moreover, no resistance to this drug has
      been recorded during induction when the usual presence of PML/RAR alpha was
      confirmed by molecular study (some M3 cases do lack rearrangement of PML/RAR
      alpha). Paradoxically, a hypercoagulable clotting tendency may occur in these
      patients during the first month of ATRA treatment. Leucocyte activation (retinoic
      acid syndrome), often secondary to hyperleukocytosis, is prevented by early
      addition of chemotherapy when WBCs exceed defined limits, and is successfully
      treated by high dose corticosteroids. Routine acquired progressive in vivo
      resistance to all trans retinoic acid (ATRA) requires consolidation of ATRA
      induced complete remission (CR) with intensive chemotherapy. Prevention of
      relapses using maintenance therapy is questionable and has not been tested in
      randomized trials. Actually the event-free survival of APL patients treated by
      the combination of ATRA and chemotherapy is 80% at 1 year, and the cure of 50% of
      patients is within our reach.

PMID- 7815841
TI  - Monitoring of treatment outcome in acute promyelocytic leukemia by RT-PCR.
AB  - A rearrangement between the PML and RAR-alpha genes underlies the acute
      promyelocytic leukemia (APL)-specific t(15;17) translocation, leading to the
      production of a chimeric mRNA. Recent development of a reverse-transcription
      polymerase chain reaction (RT-PCR) assay for the PML/RAR-alpha hybrid has proven
      useful for rapid diagnosis and monitoring of minimal residual disease (MRD) in
      APL patients. Preliminary studies in which the prognostic significance of RT-PCR
      was evaluated indicate that this test may identify patients at high risk of
      relapse.

PMID- 7815842
TI  - Acute promyelocytic leukemia in children: experience of the Italian Pediatric
      Hematology and Oncology Group (AIEOP).
AB  - Scanty information is available on acute promyelocytic leukemia (APL) in
      children, and whether differences are present with respect to the adult form. The
      experience of the Italian Pediatric Hematology and Oncology Group (AIEOP) will be
      presented with respect to the following aspects: 1. Incidence of APL. The
      incidence of APL is generally considered to account for 3-9% of acute myelogenous
      leukemia (AML) in children and approximately 10-15% in adults. Recently a single
      Italian pediatric institution reported that APL constituted one third of observed
      acute nonlymphocytic leukemia (AnLL) cases. Data from the AIEOP cooperative study
      group have confirmed that APL in Italy is more frequently observed in children as
      compared to other countries. Environmental and/or genetic factors should be
      considered to explain such differences. 2. Diagnosis of M3v. The clinical and
      biological features of the largest series of childhood M3v will be presented and
      the problems encountered in the proper separation of 'classic' M3 and M3v in
      children will be discussed. 3. Clinical Aspects. The clinical features of the APL
      patients enrolled in the AIEOP study groups since 1989, will be presented with
      emphasis on the recent experience with the use of all-trans retinoic acid. 4.
      Analysis of PML/RAR alpha Fusion Transcripts. An RT-PCR analysis of 32 pediatric
      APL cases from cryopreserved bone marrow samples has been performed. It is
      concluded that APL in children did not differ significantly from the adult form,
      with the exception of a higher incidence of PML bcr3 breakpoint.

PMID- 7815843
TI  - Expression and ATRA-driven modulation of adhesion molecules in acute
      promyelocytic leukemia.
AB  - On fresh leukemic cells taken from 30 patients with acute promyelocytic leukemia
      (APL) the membrane expression of a series of adhesion molecules including beta 2
      integrins (CD11a/LFA-1, CD11b/Mac-1), selectin ligands (CD15/Le(x), CD15s/sLex)
      and tyrosine-phosphatase isoforms (CD45RA, CD45R0) was analyzed. The expression
      of these molecules was also studied in nine of these patients following the APL
      cells' culture with and without all-trans retinoic acid (ATRA). The fresh APL
      promyelocytes expressed CD45RA and CD15s on their surface, while CD11a, CD11b,
      CD15, and CD45R0 were constantly absent. In vitro treatment with ATRA
      consistently increased the expression of CD15, CD11b, and CD45R0 on leukemic
      promyelocytes; these changes were paralleled by a decrease of CD45RA display. The
      expression of sialylated antigen CD15s was fully independent from CD15 suggesting
      a differential enzymatic regulation within this selectin ligand system. ATRA was,
      however, incapable of promoting the up-regulation of CD11a in APL. As a result,
      asynchronous phenotype (CD11a-, CD11b+, CD15+, CD15s+/-, CD45RA-, CD45R0+) was
      generated that is normally undetectable on maturing myeloid cells. In order to
      provide a further control a case of acute agranulocytosis was also investigated,
      in which > 75% bone marrow cells were arrested at the promyelocyte stage; these
      bone marrow cells showed a surface phenotype identical to non-leukemic
      promyelocytes (CD11a+, CD11b+, CD15+, CD45R0+, CD45RA-) with a spontaneous
      ability to differentiate in vivo towards the more mature stages of myeloid
      differentiation. We therefore suggest that in fresh and ATRA-induced APL cells
      distinct, regular phenotypic changes are identifiable that are probably
      associated with t(15;17) and not seen in normal and activated bone marrow.

PMID- 7815844
TI  - All-trans retinoic acid in acute promyelocytic leukemia in late pregnancy.
AB  - All-trans retinoic acid (ATRA) was used in a case of acute promyelocytic leukemia
      (APL) in late pregnancy. A very prompt maternal risk reduction was achieved with
      subsequent complete remission and spontaneous delivery of two live children in
      whom no fetal damage seems to have occurred.

PMID- 7815847
TI  - Factors influencing young children's coping behaviors during stressful healthcare
      encounters.
AB  - The authors examined the coping behaviors of 80 preschool children during
      venipuncture, and selected situational and personal variables thought to
      influence their coping. The children's behaviors were recorded on the Children's
      Coping Strategies Checklist-Intrusive Procedures; the helpful behaviors of health
      professionals were recorded on the Nursing Actions Checklist. Information about
      specific influencing variables was gathered through questionnaires and parent
      interviews. The children's report of procedural pain was correlated with the
      number of coping behaviors used, with the children's attempts to protect
      themselves, and with helpful nursing interventions. Socioeconomic status, nursing
      interventions, and preparation for the procedure had low to moderate correlations
      with number and type of the children's coping behaviors. The results indicate
      that a child's coping is related to the situation, and the actions of
      professionals in that situation rather than to the characteristics of the
      individual child.

PMID- 7815846
TI  - Mothers' intention, age, education and the duration and management of
      breastfeeding.
AB  - The authors examined the breastfeeding duration and management of two groups of
      mothers with different exposures to services of a Certified Lactation Consultant
      (CLC). One group of mothers, at hospital H1 (n = 46), had access to a CLC, while
      mothers at hospital H2 (n = 115) did not. Results showed that: (a) mothers at H1
      had significantly (t = 2.33, p < .02) longer durations of breastfeeding (M = 3.1
      months, SD = 1.2) than peers at H2 (M = 2.4 months, SD = 1.2); (b) a
      significantly greater proportion of mothers at H1 attained their intended
      duration of breastfeeding compared to mothers at H2 (Mann-Whitney U, one-tailed
      test, Z = 1.94, p < .05); and (c) in a stepwise multiple regression analysis,
      intended length of breastfeeding accounted for 18% of the variance in duration of
      breastfeeding, mothers' age 9%, and mothers' education 3%. The results support
      the theory of reasoned action and the theory of patient education.

PMID- 7815848
TI  - The postpartum experience of low-risk women: a time of adjustment and change.
AB  - To describe the postpartal experiences of low-risk women after discharge from the
      hospital, 50 puerperal women were interviewed in their homes within 2 weeks after
      discharge from the hospital. Fatigue was identified as an underlying factor for
      many issues during this time period, including physical complications, emotional
      changes, and changes in relationships. Several women commented that their short
      hospital stays left them with too little time to recuperate before they were
      discharged from the hospital. Caregivers of childbearing women need to be
      cognizant of the needs and concerns of contemporary low-risk puerperal women to
      provide adequate education, guidance, and support.

PMID- 7815849
TI  - An integrative research review of intervention studies with premature infants
      from disadvantaged backgrounds.
AB  - The recent emphasis on intervention programs to better the prospects of children
      from poor and minority backgrounds sparked this integrative review of studies
      looking at disadvantaged families with premature infants. The author uses three
      areas to characterize the studies reviewed: The type of intervention, attrition
      rates, and outcome measures. Thirteen studies are abstracted and examined.
      Suggestions are offered related to the characteristics of successful
      interventions, how to decrease attrition rates, and which assessment measures
      should be used to improve documentation of the efficacy of interventions.

PMID- 7815850
TI  - From the rainforest to the reef: searching for bioactive natural products in the
      mid-Pacific.

PMID- 7815851
TI  - Structure-activity aspects of hemicholinium-3 (HC-3) and its analogs and
      congeners.

PMID- 7815852
TI  - Non-least-squares regression analysis applied to organic and medicinal chemistry.

PMID- 7815853
TI  - Vitamin D.

PMID- 7815854
TI  - Outpatient care of selected patients with acute non-variceal upper
      gastrointestinal haemorrhage.
AB  - Patients with upper gastrointestinal haemorrhage (UGIH) are usually cared for in
      hospital. To evaluate the efficacy and safety of outpatient care of selected
      patients with acute non-variceal UGIH who had endoscopy, we retrospectively
      analysed 4.5 years' experience of patients treated without hospital admission. We
      developed practice guidelines for outpatient care, and prospectively studied
      patients treated during the first 6 months of their use. 78 (8.4%) of 933
      patients in the retrospective series and 34 (24.1%) of 141 in the prospective
      series received outpatient care. The guidelines comprised early notification of a
      gastroenterologist, urgent endoscopy, clinical, laboratory, and endoscopic
      criteria for outpatient care, and details of care. In the prospective study
      patients treated as outpatients were younger than those admitted (52.8 [SE 3.6]
      vs 63.0 [1.5] years) and had a slightly longer time from onset of bleeding to
      endoscopy (2.4 [0.2] vs 2.1 [0.2] days). Outpatients were less likely to have
      alcoholism, other major concomitant disease, syncope or presyncope, or supine
      tachycardia. Outpatients had higher haemoglobin concentrations than inpatients
      (125 [4] vs 106 [3] g/L). Most patients in both groups had peptic ulcers. There
      were no complications in the retrospective series; 1 of the 34 prospective
      outpatients was admitted with rebleeding. All outpatients survived. The estimated
      hospital cost saved per outpatient was about $990. A substantial proportion of
      carefully selected patients with acute non-variceal UGIH can be effectively cared
      for without admission to hospital.

PMID- 7815855
TI  - Looking at modest health-care reform.

PMID- 7815856
TI  - New approaches and concepts with vaccines.

PMID- 7815857
TI  - Acinetobacter infections, intensive care units, and handwashing.

PMID- 7815858
TI  - Acinetobacter infections, intensive care units, and handwashing.

PMID- 7815859
TI  - Acinetobacter infections, intensive care units, and handwashing.

PMID- 7815860
TI  - Acinetobacter infections, intensive care units, and handwashing.

PMID- 7815861
TI  - Allotransplantation of parathyroid cells.

PMID- 7815862
TI  - Treatment of HELLP syndrome with nitric oxide donor.

PMID- 7815863
TI  - Autoantibodies to 90 kD heat-shock protein in sera of breast cancer patients.

PMID- 7815864
TI  - Hepatitis E virus and HIV infection in homosexual men.

PMID- 7815865
TI  - Overseas electives.

PMID- 7815866
TI  - Window in clouds over galactosaemia?

PMID- 7815867
TI  - Medical future for Hong Kong.

PMID- 7815868
TI  - Trends in gynaecological surgery.

PMID- 7815869
TI  - Value of mammography for women aged 40-49.

PMID- 7815870
TI  - Does surface heparinisation reduce bacterial colonisation of central venous
      catheters?

PMID- 7815871
TI  - Measurement of posterior fossa neurovascular anomalies in essential hypertension.

PMID- 7815872
TI  - Measurement of posterior fossa neurovascular anomalies in essential hypertension.

PMID- 7815873
TI  - Self-administered vaginal swabs for population-based assessment of Trichomonas
      vaginalis prevalence.

PMID- 7815874
TI  - Sertraline and platelet counts in idiopathic thrombocytopenia purpura.

PMID- 7815875
TI  - Factor V Leiden mutation and venous thrombosis.

PMID- 7815876
TI  - Factor V Leiden mutation and venous thrombosis.

PMID- 7815877
TI  - Early extubation after open-heart surgery with total intravenous anaesthetic
      technique.

PMID- 7815878
TI  - Efficacy of SPf66 vaccine against Plasmodium falciparum malaria in children.

PMID- 7815879
TI  - Regional variations in medium-chain acyl-CoA dehydrogenase deficiency.

PMID- 7815880
TI  - Chlorhexidine or polyhexamethylene biguanide for acanthamoeba keratitis.

PMID- 7815881
TI  - Telemedicine: fad or future?

PMID- 7815882
TI  - TNF and Mae West or: death from too much of a good thing.

PMID- 7815883
TI  - Preventing admissions for gastrointestinal bleeding.

PMID- 7815884
TI  - When amniotic fluid cells do not grow.

PMID- 7815885
TI  - Familial disseminated atypical mycobacterial infection in childhood: a human
      mycobacterial susceptibility gene?
AB  - Inherited defects in specific components of the immune system have provided many
      clues to the immunological mechanisms underlying resistance to microbial
      infection. We report a familial immune defect predisposing to disseminated
      atypical mycobacterial infection in childhood. 6 children with disseminated
      atypical mycobacterial infection and no recognised form of immunodeficency were
      identified. Four, including two brothers, come from a village in Malta, and two
      are brothers of Greek Cypriot origin. They presented with fever, weight loss,
      lymphadenopathy, and hepatosplenomegaly. They had anaemia and an acute phase
      response. A range of different mycobacteria (Mycobacterium fortuitum, M chelonei,
      and four strains of M avium intracellulare complex) were isolated. Treatment with
      multiple antibiotics failed to eradicate the infection, although treatment with
      gamma interferon was associated with improvement. Three have died and the
      surviving children have chronic infection. Tumour necrosis factor-alpha
      production in response to endotoxin and gamma-interferon was found to be
      defective in affected patients and their parents. T-cell proliferative responses
      to mycobacterial and recall antigens were reduced in parents of affected children
      and gamma-interferon production was diminished in the affected patients and their
      parents. Clinical and immunological features suggest that these patients are
      phenotypically similar to Lsh/Ity/Bcg susceptible mice. Understanding of this
      defect may provide insights into the mechanisms responsible for susceptibility to
      mycobacteria.

PMID- 7815886
TI  - Expectant management of first-trimester spontaneous abortion.
AB  - Approximately 15% of registered pregnancies end in spontaneous abortion, and for
      50 years or so dilatation and curettage (D&C) has been the usual management. In a
      prospective randomised trial we compared the clinical results after either
      expectant management or D&C, for miscarriages of less than 13 weeks' gestation in
      which transvaginal ultrasound examination showed intrauterine tissue and/or blood
      clots with a diameter 15-50 mm. 103 patients were randomised to expectant
      management and spontaneous resolution of pregnancy occurred within 3 days in 81
      cases (79%). 52 patients were randomised to D&C. 3 infections were diagnosed
      among patients who underwent expectant management (3%); 5 infections and 1 case
      of postoperative anaemia were observed among patients randomised to D&C (11%).
      The duration of vaginal bleeding was a mean of 1.3 days longer in the expectant
      management group (p < 0.02). Convalescence time, time during which patients
      experienced pain, and packed-cell volume 3 and 14 days after inclusion did not
      differ significantly between the groups. This study shows that expectant
      management of selected cases of spontaneous abortion has a similar outcome to
      D&C.

PMID- 7815887
TI  - Large-cell anaplastic lymphoma-specific translocation (t[2;5] [p23;q35]) in
      Hodgkin's disease: indication of a common pathogenesis?
AB  - Chromosomal aberrations are characteristic and specific events; the detection of
      chromosomal abnormalities often provides information on diagnosis and prognosis
      of disease. Some patients with large-cell anaplastic lymphoma (Ki 1 lymphoma)
      have the translocation t(2;5) (p23; q35), involving a possible growth-regulating
      tyrosine kinase. We found this translocation in 11 patients with Hodgkin's
      disease of nodular sclerosis and mixed-cellularity types. This finding has
      implications for the understanding of the relation between large-cell anaplastic
      lymphoma and Hodgkin's disease, diseases with morphological and
      immunophenotypical similarities. Study of this translocation may help
      understanding of the origins of cancer and cancer growth. It also allows a more
      precise definition of Hodgkin's disease and may be used as an indicator for
      clonality--which has long been sought.

PMID- 7815888
TI  - Effect of parkinsonian signs and symptoms of bilateral subthalamic nucleus
      stimulation.
AB  - In monkeys rendered parkinsonian, lesions and electrical stimulation of the
      subthalamic nucleus reduce all major motor disturbances. The effect of electrical
      stimulation of the subthalamic nucleus was assessed in three patients with
      disabling akinetic-rigid Parkinson's disease and severe motor fluctuations.
      Quadripolar electrodes connected to a pulse generator were implanted in the
      subthalamic nuclei on both sides. Patients were evaluated with the unified
      Parkinson's disease rating scale and timed motor tests. 3 months after surgery,
      activities of daily living scores had improved by 58-88% and motor scores by 42
      84%. This improvement was maintained for up to 8 months in the first patient
      operated upon. One patient was confused for 2 weeks after surgery, and another
      developed neuropsychological impairment related to a thalamic infarction which
      improved over 3 months. In one patient, stimulation could induce ballism that was
      stopped by reduction of stimulation. This is the first demonstration in human
      beings of the part played by the subthalamic nuclei in the pathophysiology of
      Parkinson's disease.

PMID- 7815889
TI  - Look-back study of infectivity of anti-HCV ELISA-positive blood components.
AB  - The infectivity of blood components from donors who were later found to be anti
      HCV ELISA-positive was investigated in recipients who were enrolled in a look
      back programme. Recipients received ELISA-positive blood components from donors
      who were PCR-positive and/or RIBA-2-positive (n = 22, group A) or PCR-negative
      and indeterminate or negative on RIBA-2 (n = 105, group B). 26 of 32 (81%)
      recipients of group A donors and none of 140 of group B were HCV-infected. All
      stored serum samples of previous donations (n = 172) of group A donors were anti
      HCV-positive in RIBA-3, indicating a chronic carrier state of HCV in these
      donors.

PMID- 7815890
TI  - Failure of amniotic-fluid-cell growth: is it related to fetal aneuploidy?
AB  - We investigated outcome in patients whose amniotic-fluid-cell samples showed
      unexplained growth failure in culture. 32 of 7872 amniocentesis samples were
      classified as unexplained growth failures. 10 women did not have repeat
      cytogenetic testing, but among their pregnancies there were 4 abnormal outcomes
      (1 fetal bladder-outlet obstruction, 2 stillbirths, and 1 acardiac twin). Of the
      22 patients who had repeat karyotypic analysis, 18 had normal fetal karyotypes.
      However, 4 fetuses were aneuploid (2 trisomy 21, 1 trisomy 13, and 1 Pallister
      Killian syndrome).

PMID- 7815891
TI  - Endoscopic transthoracic sympathicotomy for severe angina.
AB  - We evaluated the antianginal effects of endoscopic transthoracic sympathicotomy
      (ETS) in 24 patients not eligible for coronary bypass surgery or angioplasty. In
      this procedure, the sympathetic chain is electrocoagulated under general
      anaesthesia. No major surgical complications occurred. The frequency of anginal
      attacks was significantly reduced (p = 0.001). The mean increase in maximum
      exercise capacity was 13 (SD 21) W (p = 0.009). ST depression at maximum
      comparable workload was reduced by 0.052 (0.10) mV (p = 0.005). Global ejection
      fraction during exercise and metaiodobenzylguanidine uptake were unchanged. Heart
      rate variability analysis showed a reduction of the ratio between low and high
      frequencies at tilt test (-1.00 [0.96]; p < 0.001). We conclude that ETS can be
      done without major complications, alleviates angina, and increases maximum
      working capacity in patients with advanced coronary disease.

PMID- 7815892
TI  - Psychoneuroimmunology: interactions between the nervous system and the immune
      system.

PMID- 7815893
TI  - Trp89 in the lid of Humicola lanuginosa lipase is important for efficient
      hydrolysis of tributyrin.
AB  - To determine whether Trp89 located in the lid of the lipase (EC 3.1.1.3) from
      Humicola lanuginosa is important for the catalytic property of the enzyme, site
      directed mutagenesis at Trp89 was carried out. The kinetic properties of wild
      type and mutated enzymes were studied with tributyrin as substrate. Lipase
      variants in which Trp89 was changed to Phe, Leu, Gly or Glu all showed less than
      14% of the activity compared to that of the wild type lipase. The Trp89Glu mutant
      was the least active with only 1% of the activity seen with the wild type enzyme.
      All Trp mutants had the same binding affinity to the tributyrin substrate
      interface as did the wild type enzyme. Wild type lipase showed saturation
      kinetics against tributyrin when activities were measured with mixed emulsions
      containing different proportions of tributyrin and the nonionic alkyl
      polyoxyethylene ether surfactant, Triton DF-16. Wild type enzyme showed a Vmax =
      6000 +/- 300 mmol.min-1.g-1 and an apparent Km = 16 +/- 2% (vol/vol) for
      tributyrin in Triton DF-16, while the mutants did not show saturation kinetics in
      an identical assay. The apparent Km for tributyrin in Triton DF-16 was increased
      as the result of replacing Trp89 with other residues (Phe, Leu, Gly or Glu). The
      activities of all mutants were more sensitive to the presence of Triton DF-16 in
      the tributyrin substrate than was wild type lipase. The activity of the Trp89Glu
      mutant was decreased to 50% in the presence of 2 vol% Triton DF-16 compared to
      the activity seen with pure tributyrin as substrate.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7815895
TI  - Central nervous system demyelinating diseases and increased release of
      cholesterol into the urinary system of rats.
AB  - The question of what happens to cholesterol in the adult central nervous system
      during its slow turnover has been addressed using rats with brain and spinal cord
      labeled with [4-14C]cholesterol upon intracerebral injection of labeled
      cholesterol into rats at 10-12 days of age. At six months after injection, 14C
      was found only in the brain and spinal cord and was slowly released via the rat's
      urine. When labeled rats were given demyelinating agents (triethyl tin chloride,
      hexachlorophene, sodium cyanide) and when experimental allergic encephalomyelitis
      was induced, a measurable increase in urinary 14C label above control levels was
      found. It was concluded that there is a direct relationship between the
      experimental demyelination induced and the increased release of cholesterol
      metabolites into urine. The study suggests that a clinical method could be
      developed to determine the rate of central nervous system demyelination by
      measuring the amount of urinary cholesterol metabolites.

PMID- 7815894
TI  - Dietary fat composition and age affect synaptosomal and retinal phospholipid
      fatty acid composition in C57BL/6 mice.
AB  - The purpose of this study was (i) to determine whether dietary fat-induced
      differences in neural and retinal membranes occur when dietary fat treatment is
      implemented in aged animals and (ii) to characterize the effect of long-term
      differences in dietary fat on neural and retinal membrane composition. For the
      first objective, young (six-week-old) and old (95-week-old) mice were randomly
      assigned to beef tallow (TAL) or soybean oil (SBO) diets for eight weeks. For the
      second objective, young (four-week-old) mice consumed either TAL or SBO diets for
      99 weeks. Young and old mice challenged with a change in dietary fat for an eight
      week period showed both diet and age effects on neural and retinal phospholipid
      fatty acid composition (P < 0.05). In addition, significant diet by age
      interactions were evident. In mice that consumed TAL and SBO diets throughout
      their life, only retinal phosphatidylethanolamine (PE) 18:2n-6 and neural
      phosphatidylserine 22:5n-6, PE 18:2n-6 and phosphatidylcholine 18:2n-6 differed
      between dietary treatments (P < 0.05). Neither the unsaturation index nor the n
      6/n-3 ratio was affected by diet. Neural and retinal phospholipid fatty acid
      composition were responsive to changes in dietary fat even when the treatment was
      implemented beyond developmental or post-weanling stages. In contrast, when mice
      consumed TAL or SBO diets throughout their life, fewer differences in
      phospholipid fatty acid composition were detected, suggesting that the effect of
      the dietary treatment was mitigated by aging.

PMID- 7815896
TI  - Dietary lipids modify the fatty acid composition of cartilage, isolated
      chondrocytes and matrix vesicles.
AB  - The effects of dietary lipids on the fatty acid composition of hyaline cartilage,
      epiphyseal chondrocytes (EC) and matrix vesicles (MV) were evaluated in chicks. A
      basal semipurified diet was fed to chicks containing one of the following lipid
      sources at 70 g/kg: soybean oil, butter+corn oil, margarine+corn oil or menhaden
      oil+corn oil (MEC). Articular and epiphyseal growth cartilage were isolated from
      the proximal tibiotarsus; EC and MV were subsequently released by trypsin (EC
      3.4.21.4) and collagenase (EC 3.4.24.3) digestion followed by
      ultracentrifugation. The fatty acid composition of polar lipids in chick
      epiphyseal cartilage at three and six weeks, as well as articular cartilage, EC
      and MV at eight weeks of age revealed the presence of high levels of saturated
      and monounsaturated fatty acids (up to 85.5%) but low levels of n-6
      polyunsaturated fatty acids (PUFA) (2.6-10.2%). Mead acid (20:3n-9, > 3%) was
      also present in cartilage, EC and MV lipids, and was unaffected by the dietary
      lipid treatments. Total n-3 PUFA concentrations were the highest in cartilage, EC
      and MV of chicks consuming MEC. Feeding MEC lowered the levels of 20:4n-6 in
      cartilage, but increased 20:5n-3 levels. The data are consistent with those
      reported previously which showed that cartilage tissues are low in n-6 PUFA and
      that they contain 20:3n-9. We furthermore demonstrated that the PUFA composition
      of cartilage can be modified by dietary lipids.

PMID- 7815897
TI  - The immunosuppressive substance 2-chloro-2-deoxyadenosine modulates lipoprotein
      metabolism in a murine macrophage cell line (P388 cells).
AB  - A recently developed immunosuppressive substance, 2-chloro-2-deoxyadenosine (2
      CdA), was reported to inhibit monocyte functions at low concentration. Because
      macrophages play a key role in the formation of atherosclerotic plaques, it was
      of interest to study the effect of 2-CdA on cellular lipid metabolism. For this
      purpose we have used a macrophage cell line (P388) to perform incubation studies
      in the presence of acetylated low density lipoprotein (Ac-LDL) and 2-CdA. The
      addition of 2-CdA, in concentrations ranging from 5-20 nM, induced a dose
      dependent decrease in cellular cholesterol content and in the amount of
      extracellular [14C]oleic acid (OA) incorporated into the cholesteryl ester (CE)
      fraction. The effect was maximized at 20 nM 2-CdA with an 86% reduction in
      cholesterol esterification compared to controls (P < 0.008). To evaluate the
      mechanism of interaction of 2-CdA with cellular lipid metabolism, deoxycytidine
      (dCyt) and 3-methoxybenzamide (3-MOB), substances known to antagonize the effect
      of 2-CdA in different ways, were co-administered with 2-CdA. dCyt, a competitive
      inhibitor of dCyt kinase, which catalyzes phosphorylation to the active
      metabolite, antagonized the effects of 20 nM 2-CdA, producing significantly
      greater incorporation of extracellular [14C]OA into the CE fraction than in the
      presence of 2-CdA alone (P < 0.0086). Co-incubation with 2-CdA and the poly-ADP
      ribose synthetase inhibitor 3-MOB, which is known to render cells resistant to 2
      CdA toxicity by preventing cellular nicotinamide adenine dinucleotide (NAD)- and
      adenosine triphosphase-depletion, also reversed the effect of 2-CdA on lipid
      accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7815899
TI  - Fatty acid composition of lung, macrophage and surfactant phospholipids after
      short-term enteral feeding with n-3 lipids.
AB  - Utilization of enteral feeding modalities may prove clinically relevant for rapid
      modulation of lung phospholipid polyunsaturated fatty acids (PUFA) that serve as
      substrates for the formation of vasoactive dienoic eicosanoids. We compared the
      effects of short-term enteral feeding with formulations enriched with either fish
      (n-3) or corn (n-6) oil PUFA on the fatty acid composition of rat lung, alveolar
      macrophage and surfactant phospholipids. The diets were infused continuously for
      72 h through a surgically placed gastroduodenal feeding catheter by a syringe
      pump. The n-3 PUFA derived from the fish oil enriched diet were readily
      incorporated into the phospholipid membranes of the alveolar macrophages, lung
      tissue and pulmonary surfactant. The relative percentages of the n-3 PUFA were
      significantly higher and individual and total n-6 PUFA significantly lower in the
      macrophage, lung and surfactant phospholipids from the n-3-supplemented rats in
      comparison with those present in the rats infused enterally with the n-6 diet or
      untreated, chow-fed rats (baseline). In contrast, there was a significant
      increase in linoleic acid (18:2n-6) without modification of arachidonic acid
      (20:4n-6) in the alveolar macrophages, lung tissue and surfactant from rats
      enterally receiving the n-6 diet relative to levels measured in the rats at
      baseline. The results suggest that short-term continuous delivery of n-3-enriched
      enteral preparations can foster rapid modification of membrane phospholipid PUFA
      composition of lung tissue, alveolar macrophages and lung surfactant.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7815898
TI  - Dietary polyunsaturated fat decreases interaction between low density
      lipoproteins and arterial proteoglycans.
AB  - Polyunsaturated dietary fat (n-3 and n-6) results in less atherosclerosis in
      monkeys compared to lard (Parks, J.S., Kaduck-Sawyer, J., Bullock, B.C., and
      Rudel, L.L., Arteriosclerosis 10, 1102-1112; Rudel, L.L., Parks, J.S., Johnson,
      F.L., and Babiak, J., J. Lipid Res. 27, 465-474, 1986). We hypothesized that this
      was due, in part, to a decreased reactivity of low density lipoproteins (LDL)
      with arterial proteoglycans (PG). To test this hypothesis, cynomolgus monkeys
      were fed diets containing lard, safflower oil (n-6 polyunsaturated; Poly),
      menhanden fish oil (FO), or oleic acid-rich safflower oil (oleinate; Mono) for 14
      mon, and plasma LDL were isolated and characterized. Several properties of LDL
      thought to be important in the interaction of LDL with arterial PG were measured
      including LDL particle size, chemical composition, sialic acid content, density
      distribution, apolipoprotein E (apoE) content and cholesteryl ester transition
      temperature. Plasma LDL cholesterol concentrations (mg/dL) after 14 mon of diet
      consumption averaged (mean +/- SEM): FO (366 +/- 45), Lard (352 +/- 27), Poly
      (279 +/- 24), and Mono (230 +/- 43). The composition of LDL was similar among
      diet groups except that FO LDL were relatively depleted of cholesteryl ester and
      enriched in protein and were smaller in size. LDL sialic acid content was similar
      among diet groups (4.5-5.0 micrograms/mg LDL protein). The LDL apoE/B molar
      ratio, a measure of the apoE content per LDL particle averaged: Mono (3.0 +/-
      1.0), Poly (2.0 +/- 0.1), Lard (1.8 +/- 0.5), and FO (1.0 +/- 0.2).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7815900
TI  - Effect of dietary linseed oil on tumoricidal activity and eicosanoid production
      in murine macrophages.
AB  - Diets that contain high levels of n-3 fatty acids from fish oil have been shown
      to significantly effect macrophage cytolytic capacity, tumor necrosis factor
      alpha production and eicosanoid production. The present study was undertaken to
      determine whether n-3 fatty acids from vegetable origin [linseed oil (LIN)] would
      have the same effects on murine macrophage tumoricidal capacity and eicosanoid
      production as would fish oil. Mice were fed for three weeks diets that contained
      10% (wt/wt) of either LIN, which is high in linolenic acid (18:3n-3), menhaden
      fish oil (MFO), which is high in eicosapentaenoic (20:5n-3) and docosahexaenoic
      (22:6n-3) acids, or safflower oil (SAF), which is high in linoleic acid (18:2n
      6). In vivo- or in vitro-activated macrophages were assessed for select
      functions. As expected, macrophages from mice fed LIN and MFO produced
      significantly lower levels of both prostaglandins and leukotriene C4 when
      compared with macrophages from mice fed SAF. In addition, LIN and MFO macrophages
      were able to synthesize leuko-triene C5, which could not be produced by
      macrophages from mice fed SAF. The effects of LIN, however, were not as
      pronounced as those of MFO. With respect to specific functions, macrophages from
      mice fed LIN did not have altered cytolytic capacity when compared with
      macrophages from mice fed SAF and activated in vitro with either
      lipopolysaccharide (LPS) alone for 24 h or with LPS plus interferon gamma (IFN
      gamma) for 5 h. Diet did not significantly alter tumoricidal capacity of
      macrophages activated completely in vivo either.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7815901
TI  - Inhibition of cytolytic T lymphocyte activity by oxysterols.
AB  - The objective of this study was to investigate the effects of oxysterols (OS),
      namely 5 alpha-hydroxy-6-ketocholestanol, 6-ketocholestanol and 25
      hydroxycholesterol, on specific cell-mediated cytotoxicity by C57BL/6 spleen
      cells against P815-X2 (a DBA/2 mastocytoma) target cells. Cytolytic T lymphocytes
      (CTL) were generated by intraperitoneally injecting C57BL/6 mice with P815-X2
      tumor cells 10 d prior to the cytotoxicity experiments. Preincubation of CTL with
      10(-5) M 5 alpha-hydroxy-6-ketocholestanol and 6-ketocholestanol for 45 min in
      lipoprotein-depleted medium resulted in an inhibition of cytolytic activity (73
      and 43%, respectively) as measured by 4-h 51Cr release. At a concentration of 5 x
      10(-6) M, 5 alpha-hydroxy-6-ketocholestanol inhibited CTL activity by 65%,
      whereas 6-ketocholestanol did not elicit any inhibition. By contrast, 25
      hydroxycholesterol did not inhibit CTL at either concentration, although it is
      known to be a potent inhibitor of 3-hydroxy-3-methyl-glutaryl-coenzyme A
      reductase, the rate-limiting enzyme in the cholesterol biosynthetic pathway. When
      CTL were preincubated with OS in lipoprotein-replete medium, there was no
      inhibition of CTL activity at the respective concentrations. The results suggest
      that the inhibition of CTL activity upon short-term incubation with OS is not due
      to the inhibition of cholesterol synthesis, but may be due to the insertion of OS
      into the plasma membrane to replace cholesterol and alteration of membrane
      physical properties.

PMID- 7815902
TI  - Sterols of eustigmatophytes.
AB  - The oyster cannot synthesize sterols from smaller molecules but must obtain them
      from its diet, which consists of detritus and small organisms, i.e., mostly
      single-celled algae. Algae differ widely in their effectiveness as oyster food.
      Small (< 5 microns) algae which are abundant in sterols and polyunsaturated fatty
      acids appear to be most effective. Recent studies have shown the occurrence of
      cholesterol in strains of the unicellular algae Tetraselmis, Chaetoceros and
      Skeletonema, sometimes in large quantities. In the study reported here, six
      isolates of a recently constructed algal class, the Eustigmatophyceae, have been
      examined for sterols and fatty acids by gas chromatography and gas
      chromatography/mass spectrometry. All strains were shown to contain cholesterol
      as the principal sterol. Two isolates contained large amounts of total sterol
      (400-1000 fg/cell), and one (Sticho 0-18) also contained large amounts of
      eicosapentaenoic acid (20:5n-3). These biochemical characteristics are desirable
      in a potential food source for oysters.

PMID- 7815903
TI  - Medicare issues.

PMID- 7815905
TI  - HIV telephone consultation service.

PMID- 7815904
TI  - Medicare supplier fraud and abuse issues.

PMID- 7815906
TI  - Newborn baby AIDS vaccine program.

PMID- 7815907
TI  - The Chest Pain Evaluation Center at the University of Maryland Medical Center.

PMID- 7815908
TI  - Hospital and emergency medical services system interaction during the
      implementation of chest pain emergency rooms.
AB  - Knowledgeable personnel at 23 hospitals with chest pain emergency rooms (CPERs)
      served by nonhospital-based emergency health services (EMS) systems were
      surveyed. Although few hospitals had involved EMS in the planning stages of the
      CPER, there were no reports of a poor relationship with the local EMS system, and
      surveyed personnel perceived neither deterioration nor improvement in their
      hospital's relationship with EMS after opening the CPER. Hospitals where EMS was
      considered important to the functioning of the CPER were significantly more
      likely to have involved EMS in the CPER planning process.

PMID- 7815909
TI  - The emergency medical services board and the reorganization of the Maryland
      Institute for Emergency Medical Services System.

PMID- 7815910
TI  - The Maryland State Police Aviation Division emergency medicine protocol.

PMID- 7815911
TI  - The Shock Trauma Center at the University of Maryland Medical Center: an
      interview with John Ashworth. Interview by Vivian Smith.

PMID- 7815912
TI  - Pertinent medical intelligence: the poppy seed.

PMID- 7815914
TI  - Medicare fraud alerts.

PMID- 7815913
TI  - Acute poliomyelitis in Maryland. Clinical management. 1954.

PMID- 7815915
TI  - December, 1994. New vaccine information statements.

PMID- 7815916
TI  - Effect of iron regulation on expression and hemin-binding function of outer
      sheath proteins from Treponema denticola.
AB  - The effect of the iron-chelating compounds EDDA and BPD on polypeptide regulation
      in the putative oral pathogen Treponema denticola was studied. SDS-PAGE analysis
      of the T. denticola strains grown in the presence of EDDA or BPD, i.e. iron
      limiting environmental conditions, revealed the expression of 44 and 43 kDa
      polypeptides in the outer sheath, a 73 kDa polypeptide in the cell membrane, and
      a 16 kDa polypeptide in the soluble cell fraction. The hemin-binding activity of
      purified outer sheaths from T. denticola TD-4 grown in the presence of 6.4 mM
      EDDA was significantly greater than that observed in control (absence of EDDA)
      outer sheaths. Both activities were inhibited by proteinase K. SDS-PAGE, LDS-PAGE
      and TMBZ staining revealed the 44 and 43 kDa outer-sheath polypeptides to be
      expressed by T. denticola strains GM-1. MS-25, ATCC 33520 and ATCC 33404 (TD-4),
      strains which possessed strong hemin-binding activity. The 44 kDa hemin-binding
      polypeptide was purified by 1% CHAPS solubilization, HPLC, and SDS-preparative
      electrophoresis. N'-terminal sequence analysis indicated the purified 44 kDa
      polypeptide to belong to a new, undescribed group of polypeptides possessing
      hemin-binding activity.

PMID- 7815917
TI  - Cloning and expression of hemolysin genes from Treponema denticola strains ATCC
      35404 (TD-4) and human clinical isolate GM-1 in Escherichia coli.
AB  - The oral spirochete, Treponema denticola is a putative etiologic agent in adult
      periodontitis, and acute necrotizing ulcerative gingivitis. In vitro, the oral
      treponeme produces several factors including proteases, hemolysins, hemin-binding
      proteins, which could potentially be involved in the virulence of this
      spirochete. Our laboratory has been investigating the pathobiology of T.
      denticola, and has demonstrated the production of several hemolysins by T.
      denticola. In this report two hemolysin genes from T. denticola strains ATCC
      35404 (TD-4) and GM-1 were isolated by screening genomic DNA libraries of T.
      denticola on sheep blood agar plates. Physical maps of the insert fragments were
      not identical. Southern blot analyses suggested some degree of homology in the
      nucleotide sequence. Maxicell analyses of [35S]-methionine-labeled polypeptides
      from the recombinant plasmids have suggested the synthesis of an approximately
      62.5 kDa polypeptide. Biochemical characterization of the T. denticola hemolysin
      genes indicated the activity to be inhibited by Mg2+, Ca2+ and Zn2+ but not by
      EDTA. Dithiothreitol and glutathione moderately enhanced the hemolytic activity
      of the recombinant plasmids. Iron partially inhibited the hemolytic activities.
      Addition of 2-2' bipyridyl moderately enhanced the activities, possibly by iron
      limitation. These results suggest the isolation of an identical hemolysin gene
      from T. denticola strains TD-4 and GM-1.

PMID- 7815918
TI  - Entry of coronavirus into primate CNS following peripheral infection.
AB  - A previous report demonstrated that intracerebrally inoculated coronavirus
      produced CNS disease in two species of primates (Murray RS, Cai G-Y, Hoel K, et
      al., Virol 1992; 188: 274-84). We were therefore interested in testing the
      potential of coronaviruses to infect primate CNS tissue following peripheral
      inoculation. Four Owl monkeys (Aotus trivirgatus) were inoculated intranasally
      and ocularly and four were inoculated intravenously with coronavirus JHM OMp1
      (Murray RS, Cai G-Y, Hoel K, et al., Virol 1992; 188: 274-84). Two intranasally
      and two intravenously inoculated animals received a second intravenous inoculum
      at 153 days post-infection. The animals were sacrificed 16, 35, 194, and 215 days
      post-infection. Tissue sections from brain and spinal cord were screened for
      viral products by in sity hybridization and immunostaining. Virus RNA and/or
      antigen was detected in the brains of all animals and the distribution
      corresponded to areas of inflammation and edema. Viral products were
      predominantly found in blood vessels and perivascular regions, suggesting
      hematogenous spread with entry into the central nervous system through
      endothelium.

PMID- 7815919
TI  - Phenotypic variability of X-protein expression by mastitis-causing Streptococcus
      agalactiae of serotype NT/X and opsonic activities of specific antibodies.
AB  - This study examined the role of antibodies against the X-protein, a surface
      localized antigen frequently associated with streptococci causing mastitis in
      cattle, in the opsonization and phagocytosis of unencapsulated Streptococcus
      agalactiae. The analysis of various strains of serotype NT/X by flow cytometry,
      after labeling with a monoclonal antibody to X-protein, revealed that they
      consisted of a mixture of unstained and stained bacteria. Cloning of mother
      strains yielded clones of unstained bacteria but not homogeneous clones of
      stained bacteria. Analysis by ELISA of an unstained clone (4.1) derived from the
      reference NT/X strain 24/60 indicated that it expressed low amount of X-protein
      at its surface, about 25 times less than the stained clone 24/60 5.6. Colloidal
      gold immunolabeling showed the X-protein at the periphery of bacteria (of clone
      5.6 and in lower amount of clone 4.1), at a distance from the cell wall. Bovine
      antibodies (essentially IgG) to X-protein behaved like the monoclonal antibody in
      the cytometric assay. They activated the classical pathway of complement as shown
      by the deposition of C1q and C4 on bacteria. Deposition of C4 also occurred on
      the low-surface-producing clone 4.1 in the presence of antibodies to X-protein,
      although less efficiently than on the high-surface-producing clone 5.6. When used
      alone, antibodies promoted the ingestion of bacteria and heat-inactivated immune
      serum promoted the chemiluminescence activity and the killing by
      polymorphonuclear cells. In conclusion, antibodies to X-protein induced the
      deposition of C3 by the classical pathway and were also able to stimulate
      opsonophagocytic killing of X-bearing S. agalactiae in the absence of deposited
      C3.

PMID- 7815920
TI  - Selective permissiveness of TPA differentiated THP-1 myelomonocytic cells for
      human cytomegalovirus strains AD169 and Towne.
AB  - Two highly passaged laboratory strains of human cytomegalovirus (HCMV), AD169 and
      Towne, were tested for their ability to infect and replicate in THP-1
      myelomonocytic cells differentiated with 12-O-tetradecanoylphorbol-13-acetate
      (TPA). TPA treatment of human THP-1 cells increased the number of cells that
      expressed HCMV immediate early (IE1) antigen from 0.06% prior to TPA treatment to
      12% following cell differentiation. The Towne but not the AD169 strain replicated
      in differentiated THP-1 cells as determined by HCMV DNA replication and
      infectious virus production. Major early (HCMVTRL4) mRNA was present in both the
      abortive and productive THP-1 cell infections.

PMID- 7815921
TI  - Flagellate and non-flagellate Proteus mirabilis in the development of
      experimental urinary tract infection.
AB  - Three isolates of Proteus mirabilis from symptomatic human urinary tract
      infections (UTI) were tested for their ability to cause renal infection in mice.
      All three strains were fimbriated as tested by hemagglutination. One of the
      strains, Pr 988, did not possess flagella, whereas the other two did and were
      capable of swarming on solid rich media. We compared the capacity of these
      strains to infect mice in both the ascending and hematogenous mouse UTI models.
      Infection was assessed by counting viable bacteria in kidney and bladder
      homogenates in ascending UTI or by the presence of abscesses in the
      hematogenously inoculated mice. All three strains were able to infect mice in
      both UTI models. These results suggest that flagella are not absolutely necessary
      for virulence in these experimental models.

PMID- 7815922
TI  - Molecular evolution in the gnd locus of Salmonella enterica.
AB  - The gnd gene, the structural gene for 6-phosphogluconate dehydrogenase, was
      sequenced and analyzed in 34 isolates from different serovars of the seven
      subspecies of Salmonella enterica to provide comparative information on the
      evolution in this gene, which has been studied extensively in Escherichia coli.
      The gene tree obtained by the neighbor-joining method in general gave separate
      branches for each subspecies, with the few exceptions readily explained by
      recombination. There is evidence of recombination involving transfer of long
      (more than 400 bp) and short (30-150 bp) segments of DNA. Four of the six long
      segment transfers detected are at the 5' end of the gene, and in all four cases a
      variant of the chi sequence is located close to the recombination junction and
      appears to have mediated the recombination events. We suggest that in these four
      cases and in a fifth case with intersubspecies transfer of the whole gnd gene,
      the adjacent rfb (O antigen) locus may have been transferred in the same event.
      The estimates of the number of synonymous substitutions per synonymous site, KS,
      and the number of nonsynonymous substitutions per nonsynonymous site, KA, within
      the E. coli and S. enterica gnd genes, and also between the two species show an
      interesting distribution, with KS being lower toward the ends of the gene and KA
      in particular being lower in the first than in the second domain. In S. enterica,
      synonymous sites also seem to be subjected to negative selection. The ratio of KA
      to KS was higher within S. enterica and E. coli than between them, which may
      indicate that intraspecies variation is essentially between clones and that
      mildly deleterious mutations can be fixed within clones, which would thus raise
      KA within species.

PMID- 7815923
TI  - Evidence for effect of random genetic drift on G+C content after lateral transfer
      of fucose pathway genes to Escherichia coli K-12.
AB  - The cps cluster of Escherichia coli K-12 comprises genes involved in synthesis of
      capsular polysaccharide colanic acid. Part of the E. coli K-12 cps region has
      been cloned and sequenced and compared to its Salmonella enterica LT2
      counterpart. The cps genes from the two organisms are homologous; in the case of
      the LT2 genes, with G+C content of 0.61 and codons characteristic of high G+C
      species, it seems clear that they have been acquired relatively recently by
      lateral transfer from a high G+C species. The K-12 form of these cps genes is
      closely related to those of LT2 so must derive from the same high G+C species,
      but it appears to have transferred much earlier such that random genetic drift
      has brought P3 (the corrected G+C content of codon base 3) down from 0.77 to
      0.64, more than halfway to the E. coli average of 0.57. We estimate, using an
      equation developed by Sueoka, that the lateral transfer to E. coli took place
      approximately 45 million years ago. This is the first report we are aware of
      demonstrating the expected adjustment of P3 after lateral transfer between
      species with different G+C content DNA.

PMID- 7815924
TI  - Big flies, small repeats: the "Thr-Gly" region of the period gene in Diptera.
AB  - The region of the clock gene period (per) that encodes a repetitive tract of
      threonine-glycine (Thr-Gly) pairs has been compared between Dipteran species both
      within and outside the Drosophilidae. All the non-Drosophilidae sequences in this
      region are short and present a remarkably stable picture compared to the
      Drosophilidae, in which the region is much larger and extremely variable, both in
      size and composition. The accelerated evolution in the repetitive region of the
      Drosophilidae appears to be mainly due to an expansion of two ancestral repeats,
      one encoding a Thr-Gly dipeptide and the other a pentapeptide rich in serine,
      glycine, and asparagine or threonine. In some drosophilids the expansion involves
      a duplication of the pentapeptide sequence, but in Drosophila pseudoobscura both
      the dipeptide and the pentapeptide repeats are present in larger numbers. In the
      nondrosophilids, however, the pentapeptide sequence is represented by one copy
      and the dipeptide by two copies. These observations fulfill some of the
      predictions of recent theoretical models that have simulated the evolution of
      repetitive sequences.

PMID- 7815925
TI  - Molecular evolution at subzero temperatures: mitochondrial and nuclear
      phylogenies of fishes from Antarctica (suborder Notothenioidei), and the
      evolution of antifreeze glycopeptides.
AB  - Most fishes of the perciform suborder Notothenioidei are endemic to the subzero
      marine waters of Antarctica. A number of remarkable physiological attributes
      allow them to inhabit this extreme environment; for example, the blood of almost
      all notothenioid species contains antifreeze glycopeptides. To establish a
      molecular phylogenetic hypothesis for these fishes, DNA sequences from two
      mitochondrial genes, portions of the 12S and 16S ribosomal genes (928 base pairs
      [bp]), were determined for 18 species. These belong to 15 genera in five families
      of the suborder. The DNA data suggest that two of these families are unnatural
      groups and consequently that the classification and phylogeny of this suborder is
      in need of revision. In terms of DNA variation, the Bovichtidae are a distantly
      related sister group to the other families of the suborder that includes the
      icefishes, the only vertebrates without hemoglobin. The fishes of the suborder
      (except the Bovichtidae) seem to have speciated rapidly, forming an adaptive
      radiation in the Antarctic waters. A phylogenetic analysis of published
      hemoglobin amino acid sequences for other notothenioid fishes supports these
      results from mtDNA. On the basis of molecular phylogeny, the evolution of
      antifreeze glycopeptides was studied. The age of the radiation of notothenioid
      fishes had been estimated to be at least 38 Mya. However, the level of mtDNA
      variation detected in notothenioid fishes appears to be too low to agree with
      this date of origin and might instead suggest a younger age (10-15 Mya).
      Alternatively, the low level of detected mtDNA variation would agree with the
      traditional old-age estimate if an extremely slow rate of mtDNA evolution is
      postulated for this group. This slow-rate hypothesis, if true, could be explained
      by decreased metabolic rates slowing down the tempo of molecular evolution.

PMID- 7815926
TI  - Distribution of the molossinus allele of Sry, the testis-determining gene, in
      wild mice.
AB  - When the Y chromosome of the laboratory inbred mouse strain C57BL/6 (B6) is
      replaced by the Y of certain strains of Mus musculus domesticus, testis
      determination fails and all XY fetuses develop either as hermaphrodites or XY
      females (XY sex reversal). This suggests the presence of at least two alleles of
      Sry, the male-determining gene on the Y:M. m. domesticus and B6. The B6 Y
      chromosome is derived from the Japanese house mouse, M. m. molossinus and
      therefore carries a molossinus Sry allele. As a first step to determine how the
      molossinus Sry allele evolved, its distribution pattern was determined in wild
      mice. The cumulative data of 96 M. musculus samples obtained from 58 geographical
      locations in Europe, North Africa, and Asia show the molossinus Sry allele is
      restricted to Japan and the neighboring Asian mainland and confirm that Japanese
      M. m. molossinus mice were derived in part from a race of M. m. musculus from
      Korea or Manchuria. Sry polymorphisms, as illustrated by the molossinus Sry
      allele, can serve as molecular markers for studies on the evolution of wild M.
      musculus populations and can help determine the role sex determination plays in
      speciation.

PMID- 7815927
TI  - Evolution of base composition in the insulin and insulin-like growth factor
      genes.
AB  - The genomes of homeothermic (warm-blooded) vertebrates are mosaic interspersions
      of homogeneously GC-rich and GC-poor regions (isochores). Evolution of genome
      compartmentalization and GC-rich isochores is hypothesized to reflect either
      selective advantages of an elevated GC content or chromosome location and
      mutational pressure associated with the timing of DNA replication in germ cells.
      To address the present controversy regarding the origins and maintenance of
      isochores in homeothermic vertebrates, newly obtained as well as published
      nucleotide sequences of the insulin and insulin-like growth factor (IGF) genes,
      members of a well-characterized gene family believed to have evolved by repeated
      duplication and divergence, were utilized to examine the evolution of base
      composition in nonconstrained (flanking) and weakly constrained (introns and
      fourfold degenerate sites) regions. A phylogeny derived from amino acid sequences
      supports a common evolutionary history for the insulin/IGF family genes. In cold
      blooded vertebrates, insulin and the IGFs were similar in base composition. In
      contrast, insulin and IGF-II demonstrate dramatic increases in GC richness in
      mammals, but no such trend occurred in IGF-I. Base composition of the coding
      portions of the insulin and IGF genes across vertebrates correlated (r = 0.90)
      with that of the introns and flanking regions. The GC content of homologous
      introns differed dramatically between insulin/IGF-II and IGF-I genes in mammals
      but was similar to the GC level of noncoding regions in neighboring genes. Our
      findings suggest that the base composition of introns and flanking regions is
      determined by chromosomal location and the mutational pressure of the isochore in
      which the sequences are embedded. An elevated GC content at codon third positions
      in the insulin and the IGF genes may reflect selective constraints on the usage
      of synonymous codons.

PMID- 7815928
TI  - Evolution of chicken repeat 1 (CR1) elements: evidence for ancient subfamilies
      and multiple progenitors.
AB  - Chicken repeat 1 (CR1) is an interspersed repetitive element that is a member of
      the non-long terminal repeat class of retrotransposons. A data set of chicken 95
      CR1 elements was compiled and the phylogeny of the 52 elements with the most
      complete 3' ends was examined. We interpret the branching pattern as clustering
      into at least six subfamilies, designated A-F. The presence of highly similar
      elements within the B, C, D, and F subfamilies is evidence that a distinct
      progenitor has spawned each of these subfamilies. The nucleotide divergence
      between members of subfamily C was 5%-8%, suggesting that this subfamily has
      undergone a relatively recent burst of retrotransposition. The A and E
      subfamilies may have been spawned from ancestors of these four progenitors or
      from other, distinct progenitors. The consensus sequences for the six subfamilies
      showed considerable divergence, implying that the CR1 subfamilies are ancient.
      The CR1 elements in each subfamily have truncated 5' ends and a 3' end consisting
      of > or = 2 repeats of an 8-bp sequence. We estimate that there are approximately
      100,000 CR1 elements in the chicken genome. Twelve CR1 sequences from avian
      species other than chicken were identified. Some of these sequences grouped into
      different subfamilies, demonstrating that multiple subfamilies existed early in
      avian evolution. Reptilian CR1 sequences were also identified, demonstrating that
      the CR1 element arose before the divergence of birds and reptiles.

PMID- 7815929
TI  - Unusual pattern of bacterial ice nucleation gene evolution.
AB  - Bacterial ice nucleation activity (INA+ phenotype) can be traced to the product
      of a single gene, ina. A remarkably sparse distribution of this phenotype within
      three bacterial genera indicates that the ina gene may have followed an unusual
      evolutionary path. Southern blot analyses, coupled with assays for ice-nucleating
      ability, revealed that within four bacterial species an ina gene is present in
      some strains but absent from others. Results of hybridization experiments using
      DNA fragments that flank the ina gene suggested that the genotypic dimorphism of
      ina may be anomalous. A phylogenetic analysis of 16S ribosomal RNA gene sequences
      from a total of 14 ina+ and ina- bacterial strains indicated that the ina+
      bacteria are not monophyletic but instead phylogenetically interspersed among ina
      bacteria. The relationships of ina+ bacteria inferred from ina sequence did not
      coincide with those inferred from the 16S data. These results suggest the
      possibility of horizontal transfer in the evolution of bacterial ina genes.

PMID- 7815930
TI  - Molecular adaptation of a leaf-eating bird: stomach lysozyme of the hoatzin.
AB  - This report describes a lysozyme expressed at high levels in the stomach of the
      hoatzin, the only known foregut-fermenting bird. Evolutionary comparison places
      it among the calcium-binding lysozymes rather than among the conventional types.
      Conventional lysozymes were recruited as digestive enzymes twice in the evolution
      of mammalian foregut fermenters, and these independently recruited lysozymes
      share convergent structural changes attributed to selective pressures in the
      stomach. Biochemical convergence and parallel amino acid replacements are
      observed in the hoatzin stomach lysozyme even though it has a different genetic
      origin from the mammalian examples and has undergone more than 300 million years
      of independent evolution.

PMID- 7815931
TI  - Phylogenetic position of foraminifera inferred from LSU rRNA gene sequences.
AB  - A 5'-terminal region of 1600-1800 base pairs was amplified, cloned, and sequenced
      in the large subunit rDNA (LSU rDNA) of four species of foraminifera. These
      sequences were compared with the homologous regions of 16 eukaryotic taxa in
      order to establish the phylogenetic position of foraminifera. Analysis of 610
      unambiguously aligned bases shows that foraminifera branch closely to plasmodial
      and cellular slime molds in the middle of the eukaryotic tree--that is, much
      earlier than suggested by the fossil record. These data, the first DNA sequences
      reported for foraminifera, will help analyze this class of protists and the early
      evolution of eukaryotes.

PMID- 7815932
TI  - Phylogenetic inference under the pure drift model.
AB  - When pairwise genetic distances are used for phylogenetic reconstruction, it is
      usually assumed that the genetic distance between two taxa contains information
      about the time after the two taxa diverged. As a result, upon an appropriate
      transformation if necessary, the distance usually can be fitted to a linear model
      such that it is expressed as the sum of lengths of all branches that connect the
      two taxa in a given phylogeny. This kind of distance is referred to as "additive
      distance." For a phylogenetic tree exclusively driven by random genetic drift,
      genetic distances related to coancestry coefficients (theta XY) between any two
      taxa are more suitable. However, these distances are fundamentally different from
      the additive distance in that coancestry does not contain any information about
      the time after two taxa split from a common ancestral population; instead, it
      reflects the time before the two taxa diverged. In other words, the magnitude of
      theta XY provides information about how long the two taxa share the same
      evolutionary pathways. The fundamental difference between the two kinds of
      distances has led to a different algorithm of evaluating phylogenetic trees when
      theta XY and related distance measures are used. Here we present the new
      algorithm using the ordinary-least-squares approach but fitting to a different
      linear model. This treatment allows genetic variation within a taxon to be
      included in the model. Monte Carlo simulation for a rooted phylogeny of four taxa
      has verified the efficacy and consistency of the new method. Application of the
      method to human population was demonstrated.

PMID- 7815933
TI  - A note on Sattath and Tversky's, Saitou and Nei's, and Studier and Keppler's
      algorithms for inferring phylogenies from evolutionary distances.

PMID- 7815934
TI  - The N-terminal, putative, mitochondrial targeting domain of the mitochondrial
      genome maintenance protein (MGM1) in yeast is homologous to the bacterial
      ribonuclease inhibitor, barstar.

PMID- 7815935
TI  - The bacterial phosphotransferase system: new frontiers 30 years later.
AB  - In 1964, Kundig, Ghosh and Roseman reported the discovery of the
      phosphoenolpyruvate:sugar phosphotransferase system (PTS). Thirty years later, we
      find that the PTS functions not only as a sugar-phosphorylating system, but also
      as a complex protein kinase system that regulates a wide variety of metabolic
      processes and controls the expression of numerous genes. As a result of recent
      operon- and genome-sequencing projects, novel PTS protein-encoding genes have
      been discovered, most of which have yet to be functionally defined. Some of them
      appear to be involved in cellular processes distinct from those recognized
      previously. Fundamental aspects of past and current PTS research are briefly
      reviewed, and recent advances are integrated into conceptual pictures that
      provide guides for future research.

PMID- 7815936
TI  - Signal peptides: exquisitely designed transport promoters.
AB  - Prokaryotic proteins destined for transport out of the cytoplasm typically
      contain an N-terminal extension sequence, called the signal peptide, which is
      required for export. It is evident that many secretory proteins utilize a common
      export system, yet the signal sequences themselves display very little primary
      sequence homology. In attempting to understand how different signal peptides are
      able to promote protein secretion through the same pathway, the physical features
      of natural signal sequences have been extensively examined for similarities that
      might play a part in function. Experimental data have confirmed statistical
      analyses which highlighted dominant features of natural signal sequences in
      Escherichia coli: a net positive charge in the N-terminus increases efficiency of
      transport; the core region must maintain a threshold level of hydrophobicity
      within a range of length limitations; the central portion adopts an alpha-helical
      conformation in hydrophobic environments; and the signal cleavage region is
      ideally six residues long, with small side-chain amino acids in the -1 and -3
      positions. This review focuses on the parallels between signal peptide physical
      features and their functions, which emerge when the results of a variety of
      experimental approaches are combined. The requirement for each property may be
      ascribed to a potential interaction that is critical for efficient protein
      export. The summation of the key physical features produces signal peptides with
      the flexibility to function in multiple roles in order to expedite secretion. In
      this way, nature has indeed evolved exquisitely tuned signal sequences.

PMID- 7815938
TI  - Molecular characterization of upstream regulatory sequences controlling the
      photoinduced expression of the albino-3 gene of Neurospora crassa.
AB  - In the filamentous fungus Neurospora crassa the biosynthesis of carotenoids is
      regulated by blue light, principally through transcriptional activation of some
      key genes in the carotenogenic enzymatic pathway. Here we report the
      characterization of the photoinducible promoter of the albino-3 (al-3) gene,
      encoding GGPP synthase. We have modified the 5' non-coding sequence of the cloned
      al-3 gene by deletion and site-directed mutagenesis, and we have tested the
      residual photoinducibility of the different constructs by transformation and
      subsequent analysis of gene expression in dark-grown and light-induced mycelia.
      The results indicate that a promoter region between positions -226 and -55
      contains all the necessary information for blue light photoinduction. Multiple
      regulatory elements are involved in the regulated expression of the al-3 gene.
      One (termed the APE element) is important for the light-induction switch on of
      the gene and a second belongs to the CCAAT boxes family. The putative APE element
      is also found in the promoter of other N. crassa photoinducible genes.

PMID- 7815937
TI  - Molecular characterization of the cai operon necessary for carnitine metabolism
      in Escherichia coli.
AB  - The sequence encompassing the cai genes of Escherichia coli, which encode the
      carnitine pathway, has been determined. Apart from the already identified caiB
      gene coding for the carnitine dehydratase, five additional open reading frames
      were identified. They belong to the caiTABCDE operon, which was shown to be
      located at the first minute on the chromosome and transcribed during anaerobic
      growth in the presence of carnitine. The activity of carnitine dehydratase was
      dependent on the CRP regulatory protein and strongly enhanced in the absence of a
      functional H-NS protein, in relation to the consensus sequences detected in the
      promoter region of the cai operon. In vivo expression studies led to the
      synthesis of five polypeptides in addition to CaiB, with predicted molecular
      masses of 56,613 Da (CaiT), 42,564 Da (CaiA), 59,311 Da (CaiC), 32,329 Da (CaiD)
      and 21,930 Da (CaiE). Amino acid sequence similarity or enzymatic analysis
      supported the function assigned to each protein. CaiT was suggested to be the
      transport system for carnitine or betaines, CaiA an oxidoreduction enzyme, and
      CaiC a crotonobetaine/carnitine CoA ligase. CaiD bears strong homology with enoyl
      hydratases/isomerases. Overproduction of CaiE was shown to stimulate the
      carnitine racemase activity of the CaiD protein and to markedly increase the
      basal level of carnitine dehydratase activity. It is inferred that CaiE is an
      enzyme involved in the synthesis or the activation of the still unknown cofactor
      required for carnitine dehydratase and carnitine racemase activities. Taken
      together, these data suggest that the carnitine pathway in E. coli resembles that
      found in a strain situated between Agrobacterium and Rhizobium.

PMID- 7815939
TI  - Residue threonine-149 of the Salmonella typhimurium CysB transcription activator:
      mutations causing constitutive expression of positively regulated genes of the
      cysteine regulon.
AB  - In both Salmonella typhimurium and Escherichia coli, CysB is a LysR family
      transcriptional activator, which regulates genes of the cysteine regulon.
      Transcription activation of cys genes also requires an inducer, N-acetyl-L
      serine, and cysB mutants that do not require inducer are termed constitutive,
      i.e. cysBc. After finding that two independently isolated cysBc mutants are
      substituted at amino acid residue threonine-149 (T149), we isolated the other 17
      single-amino-acid substitutions by site-directed mutagenesis. Of the 19 mutant
      alleles, 11 supported normal growth on sulphate, and nine of these were cysBc.
      Four other mutants were 'leaky' cysB+, and four were cysB-. Insertions of up to
      14 amino acids were also tolerated at T149, and two of three such mutants were
      cysBc. An allele containing a TAG translation terminator at codon 149 had no
      detectable function in a delta cysB strain, but gave a constitutive phenotype
      when introduced into either wild-type S. typhimurium or the E. coli strain NK1,
      which contains a cysB- mutation in a predicted helix-turn-helix region that
      interferes with specific binding of CysB to DNA and with autoregulation of cysB.
      The peptide encoded by the T149ter allele is proposed to interact with the wild
      type CysB peptide or with the NK1 mutant peptide to form hetero-oligomers that do
      not require N-acetyl-L-serine for cys gene activation.

PMID- 7815940
TI  - The novel lectin-like protein CHB1 is encoded by a chitin-inducible Streptomyces
      olivaceoviridis gene and binds specifically to crystalline alpha-chitin of fungi
      and other organisms.
AB  - The chb1 gene, which encodes the unique lectin-like alpha-chitin-binding protein
      CHB1 of Streptomyces olivaceoviridis, was cloned. Transformants of Streptomyces
      lividans harbouring the plasmid pCHB10 overproduced the extracellular CHB1
      protein; the protein showed neither enzymatic nor antifungal activity.
      Biochemical analyses and immunofluorescence microscopy indicated that CHB1 binds
      strongly to alpha-chitin, but neither to chitosan and beta-chitin, nor to various
      types of cellulose. Within hyphae of fungi, the relative location of crystalline
      chitin was visualized with fluorescein-labelled CHB1. These studies suggest that
      the new protein could serve as a tool to identify alpha-chitin within different
      organisms. The chb1 gene consists of a reading frame of 603 bp and its
      transcription occurred only if the Streptomyces strain was cultivated with chitin
      as the sole carbon source. The deduced mature CHB1 protein (18.7 kDa) shows no
      apparent similarity to any known protein. Within a region containing 100 residues
      of the deduced CHB1 protein, four tryptophan and two asparagine residues as well
      as one glycine and one cysteine residue were identified, the relative positions
      of which are analogous to those of several cellulose-binding domains of bacterial
      glycohydrolases. The results of spectroscopical studies suggest a possible
      involvement of tryptophan residues in the interaction of CHB1 with alpha-chitin.

PMID- 7815941
TI  - Structural identification of metabolites produced by the NodB and NodC proteins
      of Rhizobium leguminosarum.
AB  - The Rhizobium nodulation genes nodABC are involved in the synthesis of lipo
      chitin oligosaccharides. We have analysed the metabolites which are produced in
      vivo and in vitro by Rhizobium strains which express the single nodA, nodB and
      nodC genes or combinations of the three. In vivo radioactive labelling
      experiments, in which D-[1-14C]-glucosamine was used as a precursor, followed by
      mass spectrometric analysis of the purified radiolabelled metabolic products,
      showed that Rhizobium strains that only express the combination of the nodB and
      nodC genes do not produce lipo-chitin oligosaccharides but instead produce chitin
      oligomers (mainly pentamers) which are devoid of the N-acetyl group on the non
      reducing terminal sugar residue (designated NodBC metabolites). Using the same
      procedure we have shown that when the nodL gene is expressed in addition to the
      nodBC genes the majority of metabolites contain an additional O-acetyl
      substituent on the non-reducing terminal sugar residue (designated NodBCL
      metabolites). The NodBC and NodBCL metabolites purified after in vivo labelling
      were compared with the radiolabelled metabolites produced in vitro by Rhizobium
      bacterial cell lysates to which UDP-N-acetyl-D-[U-14C]-glucosamine was added
      using thin-layer chromatography. The results show that the lysates of strains
      which expressed the nodBC or nodBCL genes can also produce NodBC and NodBCL
      metabolites. The same results were obtained when the NodB and NodC proteins were
      produced separately in two different strains. On the basis of these and other
      recent results, we propose that NodB is a chitin oligosaccharide deacetylase,
      NodC an N-acetylglucosaminyltransferase and, by default, NodA is involved in
      lipid attachment.

PMID- 7815942
TI  - Threonine dehydratases of Corynebacterium glutamicum with altered allosteric
      control: their generation and biochemical and structural analysis.
AB  - Threonine dehydratase is the key enzyme in L-isoleucine synthesis, since it is
      allosterically feedback-inhibited by L-isoleucine. With the aim of obtaining
      regulatorily altered mutants of the threonine dehydratase of Corynebacterium
      glutamicum, amino acids were specifically exchanged and a new biological system
      of mutant selection was developed, based on the intoxication of Escherichia coli
      by ketobutyrate, which is the dehydratase reaction product. A collection of 19
      mutant enzymes was generated and genetically and biochemically characterized
      comprising a whole range of regulatorily and catalytically altered enzymes. Of
      particular interest is the mutant Val-323-Ala, which is characterized by the fact
      that the L-isoleucine inhibition is entirely abolished so that the enzyme is
      always present in a relaxed, high-activity state. Correspondingly, the Hill
      coefficient is 1.4, in contrast to the value of 3.4 characteristic of the wild
      type enzyme. Another peculiar mutant generated is the double mutant His-278-Arg
      Leu-351-Ser. Here, again, L-isoleucine no longer inhibits catalytic activity, but
      the effector still promotes major structural changes of the protein, as
      ascertained from the L-isoleucine-dependent loss of pyridoxal-5'-phosphate from
      this mutant enzyme. Further enzymes obtained are reduced in L-isoleucine
      inhibition to a varying degree. Detailed studies on the structure of the enzyme
      revealed a partially very high similarity of the secondary structure to the
      mechanistically identical beta-subunit of the tryptophan synthase. This provides
      further indications concerning the localization of the regulatory and catalytic
      domain of the threonine dehydratase.

PMID- 7815943
TI  - DNA polymerase III of Mycoplasma pulmonis: isolation and characterization of the
      enzyme and its structural gene, polC.
AB  - Mycoplasmas have originated from Gram-positive bacteria via rapid degenerative
      evolution. The results of previous investigations of mycoplasmal DNA polymerases
      suggest that the process of evolution has wrought a major simplification of the
      typical Gram-positive bacterial DNA polymerase profile, reducing it from three
      exonuclease (exo)-positive enzymes to a single exo-negative species. The
      objective of this work was to rigorously investigate this suggestion, focusing on
      the evolutionary fate of DNA polymerase III (Pol III), the enzyme which Gram
      positive bacteria specifically require for replicative DNA synthesis. The
      approach used Mycoplasma pulmonis as the model organism and exploited structural
      gene cloning, enzymology, and Pol III-specific inhibitors of the HPUra class as
      investigative tools. Our results indicate that M. pulmonis has strongly conserved
      a single copy of a structural gene homologous to polC, the Gram-positive
      bacterial gene encoding Pol III. M. pulmonis was found to possess a DNA
      polymerase that displays the size, primary structure, exonuclease activity, and
      level of HPUra sensitivity expected of a prototypical Gram-positive Pol III. The
      high level of sensitivity of M. pulmonis growth to Gram-positive Pol III
      selective inhibitors of the HPUra type strongly suggests that Mycoplasma has
      conserved not only the basic structure of Pol III, but also its essential
      replicative function. Evidence for a second, HPUra-resistant polymerase activity
      in M. pulmonis is also described, indicating that the DNA polymerase composition
      of Mycoplasma is complex and closer to that of Gram-positive bacteria than
      previously thought.

PMID- 7815944
TI  - The 100 kDa haem:haemopexin-binding protein of Haemophilus influenzae: structure
      and localization.
AB  - All Haemophilus influenzae strains have an absolute requirement for exogenously
      supplied haem for aerobic growth. A majority of strains of H. influenzae type b
      (Hib) produce a 100 kDa protein which binds haem: haemopexin complexes. This 100
      kDa haem:haemopexin binding protein, designated HxuA, was originally detected on
      the Hib cell surface. Monoclonal antibody (mAb)-based analyses revealed that the
      HxuA protein was also present in soluble form in Hib culture supernatants. This
      soluble HxuA protein exhibited haem:haemopexin-binding activity in a direct
      binding assay. Nucleotide sequence analysis of the hxuA gene from Hib strain
      DL42, together with N-terminal amino acid analysis of HxuA protein purified from
      Hib culture supernatant, revealed that this protein was synthesized as a 101 kDa
      precursor with a leader peptide that was removed to yield a 99 kDa protein.
      Southern blot analysis of chromosomal DNA from four Hib and four non-typeable H.
      influenzae (NTHI) strains detected the presence of a single band in each strain
      that hybridized a Hib hxuA gene probe. Subsequent analysis of these NTHI strains
      showed that all four strains released into culture supernatant a haem:haemopexin
      binding protein that migrated in SDS-PAGE at a rate similar or identical to that
      of the Hib HxuA protein. A Hib hxuA mutant was used to screen an NTHI genomic DNA
      library and an NTHI gene was cloned that complemented the mutation in this Hib
      strain. Nucleotide sequence analysis of this NTHI gene revealed that it encoded a
      protein with 87% identity to the Hib HxuA protein.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7815946
TI  - Specific initiation of transcription at a cyanobacterial promoter with RNA
      polymerase purified from Calothrix sp. PCC 7601.
AB  - Although in cyanobacteria many genes have been shown to be transcriptionally
      controlled by specific stimuli, little is known about promoter structure and the
      form of RNA polymerase that recognizes individual promoters. RNA polymerase
      holoenzyme has been purified from Calothrix sp. PCC 7601. Its polypeptide
      composition resembles that of the plant chloroplast enzymes. To study
      transcription in cyanobacteria further, we have analysed the promoter-recognition
      properties of the purified enzyme. In vitro transcription was assayed with the
      promoter of the phycocyanin gene (cpc1) that is expressed whatever the incident
      light conditions. Transcription initiation at the same start point as in vivo was
      obtained with the Calothrix sp. PCC 7601 purified enzyme and the Escherichia coli
      core enzyme supplemented with a Calothrix sp. PCC 7601 sigma factor, but not with
      the E. coli holoenzyme.

PMID- 7815945
TI  - A phosphorylated DNA-binding protein is specific for the red-light signal during
      complementary chromatic adaptation in cyanobacteria.
AB  - Complementary chromatic adaptation is a mechanism by which some cyanobacteria
      that are able to synthesize phycoerythrin can adapt their pigment
      (phycobiliprotein) content to the incident wavelengths of the light. In Calothrix
      sp. PCC 7601 it concerns phycoerythrin (cpe operon), synthesized under green
      light, and phycocyanin-2 (cpc2 operon), expressed under red light, and involves
      transcriptional controls. With cell-free extracts from Calothrix sp. PCC 7601
      grown under various light regimes, a protein designated RcaD was found by gel
      retardation experiments to specifically bind to the cpc2 promoter region and to
      be present only in red-light-grown cells. This protein was partially purified and
      its binding activity was shown to be sensitive to an alkaline phosphatase
      treatment. RcaD can protect two regions of the cpc2 promoter sequence against
      degradation by DNase I. Because its activity is detected only under the
      conditions required for cpc2 expression, we propose that RcaD is a positive
      effector of transcription.

PMID- 7815947
TI  - Investigation of the role of the disulphide bond in the activity and structure of
      staphylococcal enterotoxin C1.
AB  - The goal of this study was to investigate the role of the disulphide bond of
      staphylococcal enterotoxin C1 (SEC1) in the structure and activity of the toxin.
      Mutants unable to form a disulphide bond were generated by substituting alanine
      or serine for cysteine at positions 93 and/or 110. Although we did not directly
      investigate the residues between the disulphide linkage, tryptic lability showed
      that significant native structure in the cystine loop is preserved in the absence
      of covalent bonding between residues 93 and 110. Since no correlation was
      observed between the behaviour of these mutants with regard to toxin stability,
      emesis and T cell proliferation we conclude that SEC1-induced emesis and T cell
      proliferation are dependent on separate regions of the molecule. The disulphide
      bond itself is not an absolute requirement for either activity. However,
      conformation within or adjacent to the loop is important for emesis. Although
      mutants with alanine substitutions were not emetic, those with serine
      substitutions retained this activity, suggesting that the disulphide linkage
      stabilizes a crucial conformation but can be replaced by residues which hydrogen
      bond.

PMID- 7815948
TI  - ppGpp concentration, growth without PBP2 activity, and growth-rate control in
      Escherichia coli.
AB  - Escherichia coli strains partially induced for the stringent response are
      resistant to mecillinam, a beta-lactam antibiotic which specifically inactivates
      penicillin-binding protein 2, the key enzyme determining cell shape. We present
      evidence that mecillinam resistance occurs whenever the intracellular
      concentration of the nucleotide ppGpp (guanosine 3'-diphosphate 5'-diphosphate),
      the effector of the stringent response, exceeds a threshold level. First, the
      ppGpp concentration was higher in a mecillinam-resistant mutant than in closely
      related sensitive strains. Second, the ppGpp pool was controlled by means of a
      plasmid carrying a ptac-relA' gene coding for a hyperactive (p)ppGpp synthetase,
      RelA'; increasing the ppGpp pool by varying the concentration of lac operon
      inducer IPTG resulted in a sharp threshold ppGpp concentration, above which cells
      were mecillinam resistant. Third, the ppGpp pool was increased by using poor
      media; again, at the lowest growth rate studied, the cells were mecillinam
      resistant. In all experiments, cells with a ppGpp concentration above 140
      pmoles/A600 were mecillinam resistant whereas those with lower concentrations
      were sensitive. We discuss a possible role for ppGpp as transcriptional activator
      of cell division genes whose products seem to become limiting in the presence of
      mecillinam, when cells form large spheres. We confirmed the well-known inverse
      correlation between growth rate and ppGpp concentration but, surprisingly, for a
      given growth rate, the ppGpp concentration was lower in poor medium than in
      richer medium in which RelA' is induced. We conclude that, for E. coli growing in
      poor media, the concentration of the nucleotide ppGpp is not the major growth
      rate determinant.

PMID- 7815950
TI  - Structural analysis and molybdenum-dependent expression of the pAO1-encoded
      nicotine dehydrogenase genes of Arthrobacter nicotinovorans.
AB  - The genes of nicotine dehydrogenase (NDH) were identified, cloned and sequenced
      from the catabolic plasmid pAO1 of Arthrobacter nicotinovorans. In immediate
      proximity to this gene cluster is the beginning of the 6-hydroxy-L-niotine
      oxidase (6-HLNO) gene. NDH is composed of three subunits (A, B and C) of M(r)
      30,011, 14,924 and 87,677. It belongs to a family of bacterial hydroxylases with
      a similar subunit structure; they have molybdopterin dinucleotide, FAD and Fe-S
      clusters as cofactors. Here the first complete primary structure of a bacterial
      hydroxylase is provided. Sequence alignments of each of the NDH subunits show
      similarities to the sequences of eukaryotic xanthine dehydrogenase (XDH) but not
      to other known molybdenum-containing bacterial enzymes. Based on alignment with
      XDH it is inferred that the smallest subunit (NDHB) carries an iron-sulphur
      cluster, that the middle-sized subunit (NDHA) binds FAD, and that the largest NDH
      subunit (NDHC) corresponds to the molybdopterin-binding domain of XDH. Expression
      of both the ndh and the 6-hino genes required the presence of nicotine and
      molybdenum in the culture medium. Tungsten inhibited enzyme activity but not the
      synthesis of the enzyme protein. The enzyme was found in A. nicotinovorans cells
      in a soluble form and in a membrane-associated form. In the presence of tungsten
      the fraction of membrane-associated NDH increased.

PMID- 7815949
TI  - The opaH locus of Neisseria gonorrhoeae MS11A is involved in epithelial cell
      invasion.
AB  - In order to produce a successful infection, Neisseria gonorrhoeae (GC) must
      attach to and invade mucosal epithelial cells. To identify GC gene products
      involved in this early interaction with host cells we constructed a gene bank
      derived from a clinical isolate of GC, and isolated a clone which had the
      capacity to adhere to the human endometrial adenocarcinoma tissue-culture line
      HEC-1-B. The cloned sequence was identified as a member of the opa gene family
      whose protein products have been associated with virulence. The GC chromosome
      contains numerous variant opa genes which, in MS11, are designated opaA-K.
      Previous work showed that expression of opaC confers a highly invasive phenotype
      upon strain MS11. When our cloned opa gene was mutated and returned to the GC
      MS11A chromosome by transformation and homologous recombination, we isolated one
      transformant that was significantly reduced in its invasive capacity. The locus
      mutated in this transformant was identified as opaH. Our results indicate that
      invasiveness of GC for human epithelial cells can be determined by more than one
      opa gene in strain MS11A.

PMID- 7815951
TI  - Male-female admission differentials in state mental hospitals, 1880-1990.

PMID- 7815952
TI  - The midwife's role in abortion care.
AB  - Clandestine or unhygienic abortion is one of the five primary causes of maternal
      mortality, causing up to 200,000 deaths annually. The medical complications of
      unsafe abortion are exacerbated by the standard use of sharp curettage for
      uterine evacuation and by the need to transfer women to the highest level of the
      health system for treatment. Three ways in which midwives can begin to reverse
      this trend and improve the quality and accessibility of abortion care are to
      perform vacuum aspiration to treat incomplete abortion or for early induced
      abortion; to recognise the warning signs of incomplete abortion, provide
      emergency stabilisation and resuscitation, and offer appropriate and timely
      referral for uterine evacuation; and to provide family planning counselling and
      services, particularly to women who have experienced abortion and may be at high
      risk for future unintended pregnancies but are otherwise not reached by family
      planning programmes.

PMID- 7815953
TI  - What in the world is being done about TBAs? An overview of international and
      national attitudes to traditional birth attendants.
AB  - Many of the half million women per year who die in childbirth are attended by
      traditional birth attendants (TBAs). Whether they fare better when such an
      attendant is trained remains uncertain; even the World Health Organization seems
      to have tempered its enthusiasm for TBA training recently. With some nations
      outlawing the practice of TBAs and others actively promoting it, there seems to
      be no consensus on what to do about this major and continuing workforce in
      maternity care. By themselves TBAs cannot reduce maternal mortality, whether they
      are trained or not. They need skilled, equipped and available support. As the
      professional group who must co-operate with TBAs and provide that support,
      midwives must, collectively and individually, assess, state and act on their
      attitude towards TBAs.

PMID- 7815954
TI  - Women's views of their postnatal care by midwives at an Adelaide Women's
      Hospital.
AB  - OBJECTIVE: to determine the characteristics of a sample of women giving birth in
      one hospital in South Australia and these women's perceptions of the usefulness
      of the advice and care that they were given during the puerperium DESIGN: survey
      using questionnaires, incorporating Lipsett's (1984) questions, administered
      before the women left hospital and at six weeks postdelivery. SETTING: one
      hospital in South Australia. PARTICIPANTS: a sample of convenience of 235 women
      completed the hospital questionnaire and 222 (95%) returned the six weeks
      postpartum questionnaire. FINDINGS: the women's ages ranged from 17-44 years, 86%
      were living in a stable relationship and 42% were primiparous. Most women (74%)
      made comments on the helpfulness of midwives. The midwife provided emotional
      support (57%), answered questions (32%) and gave information (30%). However,
      midwives' attitudes were perceived as insensitive (18%) and judgemental (9%).
      Midwives gave conflicting advice (10%) and 40% of the women made one or more
      comments about midwife unhelpfulness. Sixteen per cent of the women made no
      comment on the helpfulness of the midwife. IMPLICATIONS FOR PRACTICE: contact
      with midwives in the early postnatal period is an ideal time for helpful advice
      and support to be given but midwives are not always perceived as fulfilling this
      part of their role. There is a need to address the issue of conflicting advice.

PMID- 7815955
TI  - 'They know best': women's perceptions of midwifery care during labour and
      childbirth.
AB  - The aims of the study were to examine women's experiences of their labour and the
      birth of their baby. The use of qualitative method ensured that the research
      focused on the perspectives of the participants. The purposive sample consisted
      of 11 women volunteers in a maternity unit of a general hospital. Unstructured,
      tape-recorded interviews provided an opportunity for the informants to express
      their thoughts and feelings. The constant comparative method, a feature of
      Grounded Theory, was used to analyse the data. The research demonstrated that
      women trust midwives because the latter are seen as experts who 'know best'. In
      doing so, women place themselves in the hands of professionals giving them the
      authority to make decisions about procedures, drugs and types of care. This
      belief in the professionals' expertise influences the type of relationship
      between the women and midwives. Nevertheless, women also want to take an active
      part in the control of labour. The study identified a need for a flexible
      relationship between women in labour and their midwives.

PMID- 7815956
TI  - Moving towards a common understanding in maternity services.
AB  - There is a need to ensure that there is a common understanding of what is meant
      by the terminology surrounding the organisation and provision of maternity
      services. This is especially important with the development of purchaser/provider
      contracts in the National Health Service (NHS) in the UK. It is vitally important
      that terms specified in contracts are not ambiguous. It is also important that
      practitioners and researchers are working from a common base. Information on
      local definitions used in Scottish health boards was obtained through
      questionnaires sent to Heads of Midwifery Services in consultant units. The
      findings show that for some terms the definitions were fairly standard, but for
      others there were considerable differences in how the terms were interpreted. In
      light of these differences, and given the necessity for clearly defined terms
      within the new NHS, professionally agreed definitions were produced by the Royal
      College of Midwives. It is recommended that these definitions be adopted as
      standard by relevant individuals and groups.

PMID- 7815957
TI  - Michael Harbut, MD Rwanda diary: "I knew I could help people to live".

PMID- 7815958
TI  - New antitrust guidelines provide safety zones for physicians.

PMID- 7815959
TI  - Outcomes measurement--Part II. A profile of one organization's exploration of
      quality measurement and improvement.

PMID- 7815960
TI  - Article on Detroit-Macomb Hospital Center bylaws dispute draws fire. Article
      inaccurate.

PMID- 7815961
TI  - Molecular interactions between G-actin, DNase I and the beta-thymosins in
      apoptosis: a hypothesis.
AB  - The beta-thymosins are a family of < 5kDa (MW), mostly acidic, proteins which
      were originally defined in the immune system. Recently, specific members of this
      family of cytoplasmic polypeptides, namely beta-4 and beta-10, were shown to bind
      monomeric G-actin both in vitro and in vivo. Whilst many aspects of programmed
      cell death or 'apoptosis' remain to be defined, the Ca2+/Mg(2+)-dependent
      endonuclease, DNase I does feature in this process. Monomeric G-actin binds to
      and inhibits the DNA-degrading activity of DNase I. Given that the intracellular
      abundance of thymosins beta-4 and beta-10 is related to cell division and
      differentiation and that anticancer/morphogenic agents such as retinoic acid (RA)
      and cyclic AMP modulate expression of their respective genes, it is possible that
      these G-actin sequestering proteins play significant roles in apoptosis perhaps
      mediated via DNase I.

PMID- 7815962
TI  - Calcineurin as a possible new target for treatment of Parkinson's disease.
AB  - It is hypothesized that the immunosuppressive agents cyclosporin A and FK-506 may
      elicit a dopamine-like effect upon dopaminoceptive neurons in the striatum. When
      complexed to their immunophilins, these molecules will inhibit calcineurin
      activity leading to increased phosphorylation of dopamine- and cAMP-regulated
      phosphoprotein (DARPP-32) and hence, inhibition of protein phosphatase-1
      activity. As a net result, intracellular protein phosphorylation increases. One
      or more of these proteins may, in their phosphorylated form, inhibit the
      depolarization of the neurons, resulting in a dopamine-like effect.

PMID- 7815963
TI  - Bartonella bacilliformis or a similar organism and cardiovascular disease.
AB  - Bartonella bacilliformis invades the endothelial lining of the cardiovascular
      system. Damage to the red blood cells and white blood cells, the effects of the
      toxins, invasion of the brain and electrical charges induced by the organism so
      interfering with normal electrical stimulation of the heart may explain many of
      the features of cardiovascular disease (1-5).

PMID- 7815964
TI  - Hsc70/uncoating ATPase activation--proposal of a new model.
AB  - To the best of my knowledge, the signal for the clathrin removal from coated
      vesicles by the uncoating ATPase is still obscure. I presume that a specific
      configuration of preexisting, but separately ineffective uncoating ATPase binding
      sites, is responsible for the triggering of its action. Changes in the
      geometrical structure of clathrin that inevitably appear during the coated pit
      coated vesicle conversion, place the preexisting uncoating ATPase recognition
      sites into the necessary disposition.

PMID- 7815965
TI  - Percutaneous radiofrequency ablation of the left bundle branch: an alternative
      modality of treatment for patients with hypertrophic obstructive cardiomyopathy.
AB  - Hypertrophic obstructive cardiomyopathy (HOCM), which is characterized by
      asymmetric septal and ventricular obstructive hypertrophy, is currently palliated
      with a number of pharmacological, electrical and surgical interventions. Although
      none of the methods have been successful in reducing the incidence of sudden
      death, most of the patients have shown significant symptomatic improvement.
      Currently, pacemaker implantation and surgical procedures have been offered only
      to those patients who do not respond to a medical line of treatment. Since
      obstructive pressure gradients correlate fairly well with the clinical condition
      of a patient, the principal aim of surgical or pacemaker therapy has been to
      reduce the left ventricular pressure gradient. Surgical procedure achieves this
      objective by septal myotomy and myectomy whereas pacemakers attain it by altering
      the sequence of electrical stimulation of the ventricles. A right ventricular
      pacing, which behaves like a left bundle branch block, is known to alter the
      pattern of interventricular septal contraction and hence delay the onset of
      mitral leaflet-septal contact. The latter has been implicated in the pathogenesis
      of subvalvar dynamic left ventricular outflow tract obstruction, which is the
      hallmark of this condition. Currently, radiofrequency ablation of the left bundle
      branch has been successfully carried out for patients with resistant macrore
      entry ventricular tachycardia, I, therefore, propose that radiofrequency ablation
      of the left bundle branch be used as a palliative procedure of choice for
      patients with HOCM who are resistant to a medical line of treatment. This would
      result in left bundle branch block which in turn would cause an altered pattern
      of septal contraction resulting in the reduction or elimination of left
      ventricular outflow tract obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7815966
TI  - From the common cold to cancer: how evolution and the modern lifestyle appear to
      have contributed to such eventualities.
AB  - This hypothesis suggests that psychosocial stress is the pivotal determinator of
      many modern day disorders in consequence to consuming today's nutritional intakes
      of ascorbic acid and sodium. For it seems, as a result of our tropical African
      evolution, present day intakes of these essential nutrients are incompatible with
      the maintenance of bodily homeostasis when the body is subjected to any form of
      stress. In addition, the climatic conditions under which most of us live are
      seemingly ill-suited to experiencing stress, since it appears that a constituent
      part of the bodily stress response remains exclusively designed to be effective
      in a hot tropical environment, where the stress can be expected to be accompanied
      by thermoregulation sweating and an overheated body. For without such an
      occurrence coinciding with stress, the stress response itself appears to have
      been transposed into a reaction that inhibits the body's ability to resist
      infection and disease.

PMID- 7815967
TI  - On the genesis of somatization disorder: the role of the medical profession.
AB  - The development of somatization disorder is supported by the way physicians focus
      on somatic complaints but fail to effectively diagnose and relieve them if a
      specific anatomic or biochemical lesion is not found. This inadequate treatment
      of somatizing patients may related to the focus of medical teaching as well as
      male skills, styles and vulnerabilities.

PMID- 7815969
TI  - The malignant stem cell.
AB  - A recent study of embryonic cells at organogenesis revealed that their nucleus
      was bare of cytoplasm along one section of the envelope, and that they formed
      aggregates in which nucleus to nucleus contact was a feature. Their behaviour
      could be divided into three stages, the first when the embryonic cell was small
      and motile, the second when cell aggregation took place and the third when
      differentiation occurred. The embryonic cell at organogenesis was considered to
      be committed and hence stem cell in nature. It is hypothesized that stem cells in
      the adult also start off as small, motile embryonic-like cells and progress
      through the same three stages. This embryonic-like structure and behaviour also
      applies to the malignant stem cell, and evidence is put forward to support this
      view. Finally the suggestion is made that metastases are due to the small size
      and motile nature of the malignant stem cell, and not due to a decrease in any
      adhesive forces between tumour cells.

PMID- 7815968
TI  - Interstitial cystitis and silk allergy.
AB  - Interstitial cystitis patients often have a history of allergies, and frequently,
      a history of gynecological or obstetric operative procedures. Silk is a potent
      antigen, and so it is suggested that the symptomatology of interstitial cystitis
      is an allergic reaction to buried silk sutures.

PMID- 7815970
TI  - Haemopoietic stem cells and basophils.
AB  - In a recent paper it was argued that all stem cells are small motile cells, the
      haemopoietic stem cell being no exception. Although haemopoietic stem cells arise
      and mature in an extravascular milieu, they are present in small numbers in the
      peripheral circulation, where they have a lymphocyte-like appearance, and in the
      peripheral circulation their fate can be linked to the development of basophils.
      The basophil is a cell shrouded in mystery, and one of the most mysterious
      aspects of the basophil is its small numbers in bone marrow, a finding which does
      not fit in with a marrow origin. A simple experiment provides an alternative
      explanation as to how they develop. If peripheral blood smears are prevented from
      drying out, after a few hours new basophils develop from a lymphocyte-like cell.
      The findings suggest that the basophil may arise, not in the marrow, but in the
      peripheral circulation, and may represent an aberrant development of the
      haemopoietic stem cell caused by the plasma. The pathology of the basophil
      supports this view.

PMID- 7815971
TI  - Prolactin in winter depression.
AB  - Women with winter depression have low serum prolactin concentration that is
      independent of both season and efficient bright light treatment administered in
      winter. A defect of neural pathways afferent to the paraventricular nucleus may
      explain these findings. Estrogen is thought to play a key role in modulation of
      the rhythmic responses in winter depression.

PMID- 7815972
TI  - Involvement of melatonin and serotonin in winter depression.
AB  - The phase of circadian rhythms can be shifted by exposure to light. Most patients
      with winter depression are suggested to have a phase delay in their circadian
      rhythms. The efficacy of light in treatment of winter depression is thought to be
      associated with the phase shifting effect of light. In addition to light,
      melatonin and serotonin can cause phase shifts of the rhythms. The concerted
      action of these indoleamines may underly the finding that light has an
      antidepressant effect, independently of time of day or circadian phase of an
      individual.

PMID- 7815973
TI  - The yeast killer phenomenon: a hypothetical way to control Pneumocystis carinii
      pneumonia.
AB  - Pneumocystis carinii is an important agent of pneumonia in immunocompromised
      individuals, especially in acquired immunodeficiency syndrome AIDS patients P.
      carinii attaches specifically to type 1 pneumocytes. Although this phenomenon
      must play a marked role in pneumocystosis pathophysiology, no therapeutic
      molecules able to inhibit specifically the parasite attachment were found. A
      killer toxin, secreted by the yeast Pichia anomala, induced a significant
      decrease in P. carinii in vitro attachment and inhibited the parasite infectivity
      in SCID mice. Killer toxins cannot be used as systemic antibiotics. However, it
      was possible to produce antiidiotypic antibodies against a monoclonal antibody
      specific of the toxin active site. These antilds were shown to mimic the in vitro
      killer effect for the toxin and were called 'antibiobodies'. The susceptibility
      of P. carinii to the antimicrobial activity of the killer toxin made it possible
      to hypothesize that the killer phenomenon could constitute a new way for the
      treatment and prophylaxis of P. carinii infections.

PMID- 7815974
TI  - The role of immunoglobulin binding factors in the pathogenesis and therapy of
      AIDS.
AB  - The human immunodeficiency virus (HIV) gp120 and gp41 envelope proteins and
      Staphylococcus aureus protein A (SPA) all have Fc receptor (FcR)-like
      immunoglobulin binding factor (IBF) activity for the Fc constant fragments of
      human immunoglobulin G (IgG). Viral IBF may contribute to the pathology of HIV by
      jamming the network of FcR signals that control FcR-dependent immunity.
      Conversely, the bacterial IBF SPA has anti-retroviral activity that may involve
      antagonism of the immunopathological action of viral IBF, strongly suggesting IBF
      may act as a double-edged sword that might be turned against viral invaders.

PMID- 7815975
TI  - Vanadate, molybdate and tungstate for orthomolecular medicine.
AB  - Recent studies indicate that oxyanions, such as vanadate (V) or vanadyl (IV),
      cause insulin-like effects on rats by stimulating the insulin receptor tyrosine
      kinase. Tungstate (VI) and molybdate (VI) show the same effects on rat adipocytes
      and hepatocytes. Results of uncontrolled trials on volunteers accumulated in
      Japan also suggest that tungstate effectively regulates diabetes mellitus without
      detectable side effects. Since these oxyanions naturally exist in organisms,
      oxyanion therapy, the oral administration of vanadate, vanadyl, molybdate, or
      tungstate, can be considered to be orthomolecular medicine. Therefore, these
      oxyanions may provide a viable alternative to chemotherapy. Many diseases in
      addition to diabetes mellitus might also be treated since the implication of
      these results is that tyrosine kinases are involved in a variety of diseases.

PMID- 7815977
TI  - Murders--home and away.

PMID- 7815976
TI  - Is interstitial cystitis an infectious disease?
AB  - Interstitial cystitis (IC) is manifest by years of urinary frequency, urgency,
      and bladder pain and on cystoscopy, is diagnosed by petechial hemorrhages or
      ulcers. The etiology is unknown; the prominent theories are that IC is an
      autoimmune disease or is linked to increased permeability of the bladder mucosa.
      Although sought, no infectious agent has ever been identified. The disease has
      many characteristics of a chronic infection and the author's opinion is that an
      infectious disease has not been properly ruled out. To do so would require
      culture of bladder epithelium (not just urine) using special culture and non
      culture techniques such as polymerase chain reaction. Infection can easily be
      integrated into the autoimmune and permeability theories of IC pathogenesis. A
      possible analogue for this disease is chronic gastritis in which Helicobacter
      pylori has been identified as an etiological agent.

PMID- 7815979
TI  - In the public interest.

PMID- 7815978
TI  - Why are opinions about the effects of health care so often wrong?

PMID- 7815980
TI  - "High risk" postmortems.

PMID- 7815981
TI  - Fluticasone propionate nasal spray for allergic rhinitis.

PMID- 7815982
TI  - Use of nicotine to stop smoking.

PMID- 7815983
TI  - [Carbohydrate substitutes: comparative study of intestinal absorption of
      fructose, sorbitol and xylitol].
AB  - BACKGROUND: The carbohydrate substitutes fructose, sorbitol and xylitol are
      gaining more and more importance in the production of dietary food. But they can
      provoke gastrointestinal side-effects. In a randomized double blind study the
      rate of malabsorption of these sugars was compared and the concomitant symptoms
      were recorded. SUBJECTS AND METHODS: 25 healthy controls received 25 g of each
      sugar within 3 consecutive days. The intestinal absorption was determined by H2
      exhalation tests and the clinical symptoms were recorded. RESULTS: The rate of
      malabsorption was 84% for sorbitol, 36% for fructose and 12% for xylitol (p <
      0.01 for sorbitol versus fructose and xylitol). 57% of the participants with
      pathological H2-test after sorbitol and 56% after fructose reported symptoms,
      while all of the 3 malabsorbers of xylitol were symptomatic. CONCLUSIONS: There
      is an advantage to administering xylitol and fructose with regard to the
      intestinal absorption and concomitant symptoms as compared with sorbitol. H2
      exhalation tests appear to be a reliable diagnostic tool to detect carbohydrate
      malabsorption and should find broader application in patients suffering from non
      specific abdominal complaints.

PMID- 7815984
TI  - Oral supplements in HIV-infected patients with chronic wasting. A prospective
      trial.
AB  - AIM: Supplementation with polymeric formula diet was evaluated as second step of
      a nutritional intervention program for malnourished, but otherwise clinically
      stable HIV-infected patients. PATIENTS AND METHODS: 34 patients with weight loss,
      without opportunistic infections, diarrhea or fever, not responding to
      nutritional counselling as first intervention, were included. They were given
      1000 kcal per day as polymeric formula. If further weight loss occurred, dose was
      increased to 1500 kcal per day. Nutritional status was determined by body weight
      and bioelectrical impedance. RESULTS: After four weeks, 7/34 patients already
      stopped intake. Only 10/34 patients completed three months of treatment. The
      average intake during three months was 496 +/- 363 kcal/d. Reasons for drop-out
      were intervening clinical deterioration in eight, early improvement in six, but
      intolerance or loss to follow-up in ten patients. On average, body weight did not
      change. Intake of formula diet and weight changes were not correlated.
      CONCLUSION: Oral supplements are a feasible, cost-effective and safe treatment of
      malnutrition, but they are accepted only for short time and in limited amount. To
      estimate efficacy of this treatment, clinical reasons for malnutrition must be
      considered. More effective nutritional treatments are needed for chronically
      malnourished HIV infected patients.

PMID- 7815985
TI  - [The value of thallium myocardial scintigraphy (single photon emission
      computerized tomography, SPECT) for diagnosis of ischemia after myocardial
      infarct].
AB  - BACKGROUND: Patients with prior myocardial infarction and additional stenosis in
      noninfarct-related coronary artery have a high risk of reinfarction. Angina
      pectoris and exercise electrocardiography have a low sensitivity und specificity
      in detection of such coronary artery stenosis. We assessed the diagnostic value
      of tomographic thallium scintigraphy for detection of ischemia in myocardium not
      supplied by the infarct-related coronary artery. PATIENTS AND METHOD: In 77
      patients with prior myocardial infarction (59 patients with acute infarction, 18
      patients with chronic infarction) sensitivity and specificity of angina pectoris,
      exercise electrocardiography and tomographic thallium scintigraphy was
      determined. Coronary arteriography was the gold standard method. The predictive
      value of tomographic thallium scintigraphy was assessed by serial testing.
      RESULTS: Tomographic thallium scintigraphy detected 40 of 51 patients with
      significant stenosis in noninfarct-related coronary artery (sensitivity: 78%;
      positive predictive value: 83%). In 18 of 26 patients with no additional
      significant stenosis tomographic thallium scintigraphy did not show ischemia at a
      distance (specificity: 69%; negative predictive value: 62%). In sequential
      testing tomographic thallium scintigraphy did not give any additional diagnostic
      information in patients with angina pectoris. In patients without angina pectoris
      exercise electrocardiography had a high positive predictive value (90%),
      tomographic thallium scintigraphy did not yield a higher positive result. Only in
      patients without angina pectoris and negative exercise electrocardiographic
      findings tomographic thallium scintigraphy was helpful: 16 of these patients had
      an additional coronary artery stenosis and were detected by tomographic thallium
      scintigraphy only (positive predictive value: 75%); in 13 of 17 patients without
      an additional coronary artery stenosis thallium scintigrams were negative
      (negative predictive value: 76%). CONCLUSION: The presence of significant
      coronary artery stenosis in noninfarct-related vessels can be predicted by serial
      noninvasive testing. Tomographic thallium scintigraphy has its place in
      postinfarction patients without angina and with negative exercise
      electrocardiographic findings.

PMID- 7815986
TI  - [Treatment of chronic constipation with physiologic Escherichia coli bacteria.
      Results of a clinical study of the effectiveness and tolerance of microbiological
      therapy with the E. coli Nissle 1917 strain (Mutaflor)].
AB  - AIM: A randomized, double-blind clinical trial including a change-over of
      medication was carried out for 9 weeks to investigate the efficacy of an E. coli
      preparation. The study's main objective was to prove that patients of the verum
      group had 1.5 stools/week more than placebo patients after a therapeutic period
      of just 4 weeks. Stool consistency as well as efficacy and compatibility of the
      medication as judged by doctor and patient were additional criteria. PATIENTS AND
      METHOD: For a 7-day run-in phase 134 patients were recruited who had suffered
      from constipation for 18.8 years in average. In this initial phase 64 patients
      evacuated more than 2 stools per week and were excluded from the study. The
      remaining 70 patients entered the therapeutic phase being randomly distributed
      amongst verum and placebo medication. After 4 weeks of therapy patients who
      delivered 2 or less stools/week obtained the alternative medication (change
      over). RESULTS: Within the 4th week of therapy the average number of stools per
      week from patients treated with the E. coli preparation (4.9) was already
      significantly higher than from placebo-treated patients (2.6; p < 0.001). At the
      end of the 8th week of therapy the number of stools/week rose to 6.0 for verum
      treated patients, whereas for the placebo-treated control group a decrease in
      stool frequency was observed (1.9 stools/week). The results of change-over
      patients confirmed the data of the therapy weeks 1 to 4. CONCLUSION: The E. coli
      preparation proved to be successful in the therapy of the idiopathic chronic
      constipation almost free of side effects.

PMID- 7815987
TI  - [Regression of hard exudates in diabetic background retinopathy in therapy with
      etofibrate antilipemic agent].
AB  - BACKGROUND: The aim of this pilot study was to investigate the influence of a
      lipid lowering therapy with etofibrate on the progression of diabetic background
      retinopathy in patients with diabetes mellitus and combined hyperlipoproteinemia.
      In addition to the well known correlation between the duration of diabetes and
      the quality of blood glucose control, a correlation between diabetic
      microangiopathy and elevated triglyceride levels is discussed for many years. The
      most important pathogenic mechanisms in this respect seem to be an elevation of
      blood viscosity and alterations in the fibrinolytic system. Fibrinogen and
      triglycerides are the main determinants of plasma viscosity. As lipid lowering
      drugs containing fibrates and nicotinic acid are able to lower triglycerides and
      fibrinogen effectively, a favourable therapeutic effect on the progression of
      diabetic retinopathy may be expected. PATIENTS AND METHOD: 11 type II diabetics
      with combined hyperlipoproteinemia (Fredrickson type IIb) and mild to moderate
      background retinopathy detected by fundus photography were treated with
      etofibrate (2 x 500 mg/day) for a period of 6 months. RESULTS: In 7 of 10
      patients hard exudates, which had been present at the beginning of treatment,
      showed clear regression at the end of the treatment period. Among the laboratory
      test parameters a significant 30% reduction of triglycerides (p < 0.010) was
      observed. There was also a clear 25% increase in HDL cholesterol and a 12%
      fibrinogen reduction. Considerable changes of the quality of blood glucose
      control were not evident during the treatment period. CONCLUSION: Treatment with
      the lipid lowering drug etofibrate seems to produce favourable therapeutic
      effects on hard exudates in diabetic background retinopathy in patients with
      diabetes mellitus and combined hyperlipoproteinemia. The mechanisms of this
      effect are not yet clearly understood, in addition to positive effects on the
      microcirculation of the retina by lowering blood viscosity there is a direct
      lipolytic effect in the area of hard exudates to be discussed, too. It is
      important to point out that we did not see any positive effect of etofibrate
      therapy concerning other morphological changes of diabetic background
      retinopathy, i.e. microaneurysms or hemorrhages in our pilot study.

PMID- 7815988
TI  - [Clinical steps in diagnosis].

PMID- 7815989
TI  - [Bilateral salivary gland swelling with pitfalls].

PMID- 7815990
TI  - [Limits and value of chemotherapy in elderly patients].

PMID- 7815991
TI  - [The value of laboratory studies for diagnosis of osteoporosis].

PMID- 7815992
TI  - [Preventive effects of nitrates in and after myocardial infarct].

PMID- 7815993
TI  - [Deep small intestine obstruction with perforation: a complication of
      percutaneous endoscopic gastrostomy (PEG)].

PMID- 7815994
TI  - [Polycythemia as a paraneoplastic syndrome in hepatocellular carcinoma].

PMID- 7815995
TI  - [Antimicrobial therapy in neutropenia].

PMID- 7815996
TI  - Ultrasound bone velocity and metacarpal radiogrametry in hemodialyzed patients.
AB  - Bone density measurements based on the rate of propagation of ultrasound waves
      provide information on bone elasticity, which is largely dependent on cortical
      bone structure. Both bone density and cortical bone present variations dependent
      on age and sex. As far as we know, bone elasticity in patients on hemodialysis
      has not been studied, so we used ultrasound bone velocity and metacarpal
      radiogrametry to study 23 adult patients with end-stage renal disease. The
      patients' results were compared with those of a group of 23 healthy subjects
      matched by age and sex. The measurements obtained by both ultrasound bone
      velocity and metacarpal radiogrametry were lower in hemodialyzed patients (p <
      0.025) than in controls and there was a good correlation between the two
      measurements (r2 = 0.561; p < 0.0007). Neither of the measurements correlated
      with age or time on dialysis. These results show that bone elasticity in dialyzed
      patients is diminished, which could be an important factor in the bone lesions of
      these patients.

PMID- 7815997
TI  - Carcinoid tumor of the lung and type-1 multiple endocrine neoplasia associated
      with persistent hypercalcemia: a case report.
AB  - The clinical and laboratory data, and histologic, electron microscopic and
      immunocytochemical findings of a carcinoid tumor of the lung associated with
      parathyroid hyperplasia and persistent hypercalcemia are described. The carcinoid
      tumor consists of uniform cuboidal cells with regular round vesicular nuclei and
      eosinophilic granular cytoplasm. The tumor cells were chromogranin and neuron
      specific enolase positive. The CAT scan of the abdomen revealed an adrenal mass,
      3 cm in diameter, and an enlarged body in the pancreas. Our patient is still
      suffering from hypercalcemia and renal colic, despite repeated parathyroid gland
      removal, and enucleation of the lung mass. Recent parathyroid scintigraphy with
      Tc revealed an enlarged parathyroid gland. The thoracic CAT scan is normal. We
      believe that our patient is suffering from multiple endocrine neoplasia type-1
      with persistent hypercalcemia due to hyperparathyroidism.

PMID- 7815998
TI  - Total and regional bone mineral content in primary hyperparathyroidism: sex
      differences.
AB  - Changes in cortical and trabecular bone mass occurring in primary
      hyperparathyroidism are the subject of controversy. We measured the total and
      regional bone mass in a group of patients and controls and analyzed the observed
      changes with respect to sex and other characteristics. Parathormone, serum
      calcium, serum phosphorus, tubular resorption of phosphates, alkaline
      phosphatase, and tartrate-resistant acid phosphatase differed significantly (p <
      0.001 for all) between patients and controls. All the patients had significantly
      less total and regional bone mass; the regional bone mass of the arms did not
      differ. When analyzed according to sex, we found that women had a significant
      reduction in bone mass in all the zones studied (p < 0.001), whereas men had a
      significant decrease in bone mass only in the head (p < 0.025). Our findings show
      that hyperparathyroidism is accompanied by a loss of bone mass except in the
      arms, and that predominantly both cortical bone (legs, pelvis and skull) and
      trabecular bone (trunk) are affected. This means that the skeleton suffers
      generalized bone loss and a significant reduction in total body calcium content.
      Although we did not study many men, their bone involvement was less intense, and
      there was a clear difference between the sexes in this respect.

PMID- 7815999
TI  - Influence of sex and age on biochemical bone metabolism parameters.
AB  - Age-related changes in bone metabolism are of interest in the pathogenesis of
      postmenopausal and senile osteoporosis; however, data in the literature give
      conflicting results. Thus, the aim of our study was to measure serum levels of
      osteocalcin, a specific biochemical parameter of bone formation, as well as serum
      levels of midregional parathyroid hormone (PTH) and alkaline phosphatase in
      healthy males and females of various age groups. We studied 155 healthy subjects
      (91 females, 64 males, mean age: 43 years, age range: 20-81 years). Serum levels
      of osteocalcin, alkaline phosphatase and PTH increased with age and were
      significantly higher in the postmenopausal than in the premenopausal females
      (osteocalcin: 8.7 +/- 0.4 vs. 6.5 +/- 0.3 ng/ml, p < 0.0001; alkaline
      phosphatase: 126 +/- 7 vs. 89 +/- 5 U/l, p < 0.0003; PTH: 111 +/- 10 vs. 61 +/- 9
      pmol/l, p < 0.0001). In contrast, serum levels of osteocalcin, alkaline
      phosphatase and PTH were similar in the male subjects above or below the age of
      50 years (osteocalcin: 6.5 +/- 0.5 vs. 7.2 +/- 0.4 ng/ml, non significant;
      alkaline phosphatase: 104 +/- 8 vs. 105 +/- 5 U/l, non significant; PTH: 59.6 +/-
      6 vs. 61 +/- 5 pmol/l, non significant. Serum calcitonin levels were
      significantly lower in postmenopausal women and men above 50 years of age. Our
      data suggest different age-related alterations in bone metabolism in males and
      females. The increased levels of osteocalcin, alkaline phosphatase and PTH in
      postmenopausal females give evidence of increased bone turnover in these
      subjects. In healthy men bone-specific markers remained unchanged, indicating no
      relationship between bone turnover and age.

PMID- 7816000
TI  - Intravenous versus oral calcitriol therapy in renal osteodystrophy: results of a
      prospective, pulsed and dose-comparable study.
AB  - Intravenous calcitriol is generally considered to be more efficient than oral
      administration in the treatment of secondary hyperparathyroidism of chronic renal
      failure, although a comparative and prospective study employing the same doses
      and modality of drug administration is lacking. We therefore evaluated 12
      hemodialysis (HD) patients (51.7 +/- 9.4 years, mean +/- SD, HD for 8.7 +/- 4.7
      years) with marked secondary hyperparathyroidism. Based on basal humoral and bone
      histologic parameters, we divided these patients into 2 comparable groups.
      Calcitriol (0.015 micrograms/kg) was given at the end of each dialysis
      intravenously in group A and orally in group B. Humoral parameters were evaluated
      basally and after 1, 2, 4 and 8 months. Ax bone biopsy was taken at the start and
      at the end of the study. From the first month of treatment, group A showed an
      increment in ionized calcium (from 1.28 +/- 0.08 to 1.37 +/- 0.12 mmol/l, p <
      0.01), with a reduction in intact parathyroid hormone (from 470.1 +/- 349.5 to
      255.5 +/- 256.5 pg/ml; p < 0.0003) and alkaline phosphatase (from 615.1 +/- 696.3
      to 445.3 +/- 577.7 mU/ml, p < 0.001). The occurrence of hypercalcemia prompted a
      reduction in dialysate calcium content in 4 of 6 patients after 4 months, and of
      the calcitriol dose in 2 of 4 patients after 6 months. Ionized calcium then
      turned to 1.32 +/- 0.11 (p = n.s. compared to basal) while the intact parathyroid
      hormone concentration tended to revert (363.3 +/- 360 pg/ml, p = n.s. compared to
      basal) and alkaline phosphatase remained low (420 +/- 638 mU/ml, p <
      0.0005).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7816001
TI  - Effect of oral calcium on noninvasive indices of bone formation and bone mass in
      hemodialysis patients: a randomized double-blind placebo-controlled study.
AB  - The purpose of this study was to evaluate the effect of high-dose oral calcium on
      biochemical indices of bone formation, bone bisphosphonate clearance (BBC) and
      bone mineral content (BMC) of the distal forearm in patients undergoing
      hemodialysis. Eighteen patients agreed to participate and were randomized in a
      double-blind manner to receive either 2 g elemental calcium/day (n = 9) or
      placebo (n = 9) for 6 months. Previous treatment with aluminum-containing
      phosphate binders was continued unchanged throughout the study. In the placebo
      group, serum alkaline phosphatase and osteocalcin tended to increase by 8.0 and
      10.2%, respectively, while BBC changed significantly by 49.5% (p < 0.05). In the
      calcium group the opposite was observed with small decreases in alakline
      phosphatase and osteocalcin by 8.2 and 11.0%, respectively, and no change in BBC.
      BMC decreased by 5.0% in the placebo group, but increased by 5.2% in the calcium
      group, resulting in a difference of 10.2% (p < 0.05). The present study
      demonstrates that high-dose oral calcium tends to reduce bone turnover and seems
      able to prevent bone loss in hemodialyzed patients.

PMID- 7816002
TI  - Cica clamp evaluation of parathyroid responsiveness in chronic
      hypoparathyroidism: a sequential citrate and calcium clamp study.
AB  - The objective of this study was to examine if the Cica clamp technique,
      sequential citrate and calcium administration sufficient to promote steady-state
      blood-ionized calcium concentrations (B-Ca2+) of about 0.20 mmol/l below and
      above the individual baseline concentrations, was able to produce reciprocal
      changes in serum intact parathyroid hormone [S-PTH(1-84)] in chronic surgical
      hypoparathyroidism (HP; n = 10) and chronic idiopathic HP (n = 2). The calcium
      set point according to Brown [J Clin Endocrinol Metab 1993;56:572-581] was
      calculated when possible. Data from 22 controls were included for comparison.
      Within 5-10 min B-Ca2+ lowering in responding patients with surgical HP (n = 7)
      and controls demonstrated transient S-PTH(1-84) peaks from 1.3 +/- 0.7 to 3.5 +/-
      3.2 pmol/l (p < 0.05) and from 3.4 +/- 1.2 to 19.1 +/- 6.7 pmol/l (p < 0.001),
      respectively. Subsequently S-PTH(1-84) declined to steady-state hypersecretion
      levels of about 1.9 +/- 1.2 and 8.6 +/- 2.6 pmol/l, respectively. An increase of
      B-Ca2+ made S-PTH(1-84) unmeasurable in all HP responders except one, while S
      PTH(1-84) remained measurable, 0.9 +/- 0.4 pmol/l, in all controls. In responding
      patients with surgical HP and controls the respective calcium set points averaged
      1.05 +/- 0.06 and 1.13 +/- 0.04 mmol/l, respectively (p < 0.001). The remaining
      nonresponders with surgical and idiopathic HP did not respond at all. To
      summarize, 7 out of 10 patients with surgical HP demonstrated a normal pattern of
      parathyroid response to sequential B-Ca2+ decreases and increases.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7816003
TI  - The inhibitory action of aluminum on mouse bone marrow cell growth: evidence for
      an erythropoietin- and transferrin-mediated mechanism.
AB  - Aluminum (Al) has been associated with anemia in chronic renal failure patients
      under hemodialysis as well as in Al-overloaded animals. In an attempt to
      elucidate further the mechanism of Al toxicity we have investigated the effect of
      this ion on erythropoiesis in vitro. Mouse bone marrow cells were stimulated in
      vitro with erythropoietin (Epo) in the presence of Al3+ ion and erythroid colony
      forming units were then determined. Results of this study indicate that Al
      compounds (chloride and citrate) at concentrations as low as 0.37 mumol Al/l
      inhibit erythropoiesis in vitro through a mechanism dependent upon the
      availability of transferrin to bind to aluminum. This process cannot be reversed
      by increasing Epo doses. This inhibition only occurs in the presence of Epo at
      early stages during the interaction of the hormone with its target cell.

PMID- 7816004
TI  - Increased postprandial energy expenditure in obese women after peroral K- and Mg
      phosphate.
AB  - Energy expenditure (EE) was studied in 15 obese (BMI > 27.5, median 29.2) and 15
      lean (BMI < 22.9, median 21.7) healthy, postmenopausal women before and after
      peroral orange juice with or without K- and Mg-phosphate supplementation. The
      women, 56-58 years old, were studied in a double-blind, crossover experiment on
      two separate days. They received 100 ml of orange juice (10 g of carbohydrates)
      with or without a supplement of K+ (35 mmol), Mg2+ (17 mmol) and HPO4(2-) (39
      mmol). Measurements were made before and 30 and 60 min after the stimuli. Intake
      of juice only had no effect on EE in either the lean or the obese subjects. When
      the minerals were added, EE (+6.3%; p < 0.001) increased significantly in the
      obese group with in a maximum 30 min after stimulus, while no such increase was
      seen in the lean group. The difference between the groups was significant (p <
      0.05) and so was the difference in the obese group with or without minerals (p <
      0.01). We conclude that an addition of potassium/magnesium-phosphate to glucose
      increases the postprandial thermogenesis in obese postmenopausal women, but not
      in lean ones.

PMID- 7816005
TI  - Dietary xylitol retards bone resorption in rats.
AB  - Dietary xylitol has previously been found to promote the content of calcium and
      minerals of the bone during rehabilitation following dietary calcium deficiency
      and during a normocalcemic diet in rats. This in vivo experiment was performed in
      order to study whether a short-term dietary xylitol supplementation affects bone
      resorption and calcium incorporation into bone during two different experiments
      utilizing either calcium-deficient or normocalcemic diets. Xylitol reduced bone
      resorption measured by the urinary excretion of 3H radioactivity both during
      calcium-deficient and normocalcemic diets. However xylitol reduced vitamin D
      levels only during calcium deficiency, indicating that the decreased bone
      dissolution was not associated with changes in 1,25(OH)2D3 concentration alone.
      Dietary xylitol did not alter 45Ca incorporation into bone, although this does
      not exclude the possibility that xylitol may have caused alterations in bone
      apposition. These results suggest that a short-term xylitol ingestion retards
      bone resorption in the rat.

PMID- 7816006
TI  - Effect of increased dietary phosphate intake on dopamine excretion in the
      presence and absence of the renal nerves.
AB  - Studies were performed to determine the relative contributions of the renal
      nerves and tubule synthesis to dopamine excretion during increased dietary
      phosphate intake. Rats underwent bilateral renal denervation (n = 5) or sham
      surgery (n = 5) 1 week prior to the initiation of the balance studies. All rats
      were placed in metabolic cages and fed 12 g/day of a low phosphate diet (LPD,
      0.07%, Pi) for 4 days, then high phosphate diet (HPD, 1.8% Pi) for 4 days.
      Sodium, potassium, and chloride contents were made similar in LPD and HPD by
      adding sodium chloride and potassium carbonate to the food. Urine samples were
      collected every 24 h for determination of free dopamine and electrolyte
      excretions. The mean urinary phosphate excretion for 4 days of LPD was 0.17 +/-
      0.11 mmol/day in the group with bilateral renal denervation and 0.18 +/- 0.11
      mmol/day in the group with innervated kidneys. Likewise, dopamine excretion was
      similar in both groups in the absence (2.5 +/- 0.2 microgram/day) and in the
      presence (2.3 +/- 0.1 microgram/day) of the renal nerves in rats fed LPD.
      Increasing dietary phosphate intake from 0.07 to 1.8% significantly increased
      urinary phosphate and dopamine excretions. The mean urinary phosphate excretion
      for 4 days was similar in the denervated (4.4 +/- 0.9 mmol/day) and innervated
      (4.1 +/- 0.5 mmol/day) groups. The mean urinary dopamine excretion for the 4 days
      of HPD significantly increased to 4.5 +/- 0.5 microgram/day in the group with
      chronic bilateral renal denervation and 3.7 +/- 0.2 microgram/day in the group
      with innervated kidneys. Plasma 3,4-dihydroxyphenylalanine (DOPA) and dopamine
      levels were not changed by increased dietary phosphate intake. (ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7816007
TI  - A case of temporary severe disequilibrium hypercalcemia.
AB  - We report a rare case of temporary and severe hypercalcemia: the patient, a 69
      year-old woman, was admitted to Osaka City University Hospital on July 25, 1992,
      for severe hypercalcemia. The laboratory data on admission revealed severe
      hypercalcemia (14.9 mg/dl) and renal dysfunction with increased serum creatinine
      level (2.9 mg/dl). The urinary excretion of pyridinoline and deoxypyridinoline
      was increased, and serum levels of parathyroid hormone (PTH) and 1,25
      dihydroxyvitamin D were decreased. The data suggested that increased bone
      resorption was a probable main factor in the development of the hypercalcemia.
      The development of hypercalcemia seemed to be of acute onset because of (1) her
      severe symptoms caused by hypercalcemia and (2) impaired renal function which was
      improved after normalization of serum calcium level. Combination therapy with
      saline infusion and furosemide was administered, and there was a gradual decrease
      and subsequent normalization of serum calcium level along with serum creatinine.
      Even 8 months after discontinuation of the therapy for hypercalcemia, the serum
      calcium level remained within the normal range. The measured values of serum
      factors which are suspected to have a hypercalcemic effect, such as PTH,
      parathyroid hormone-related peptide and the cytokines (interleukin-1 alpha,
      interleukin-1 beta, interleukin-2, interleukin-6 and tumor necrosis factor-alpha)
      were all within the normal range. In summary, the hypercalcemia in this patient
      was regarded to be a type of disequilibrium hypercalcemia due to a combination of
      increased bone resorption and decreased renal capacity to excrete calcium.
      Furthermore, since it was temporary and did not recur even in the absence of
      treatment, the hypercalcemia was concluded to have developed due to an imbalance
      in calcium regulation rather than as a result of organic disease.

PMID- 7816008
TI  - Comparative effect of oral or intravenous calcitriol on secondary
      hyperparathyroidism in chronic hemodialysis patients.
AB  - The suppressive effects of intravenous (IVC) and oral (ORC) 1,25(OH)2D3
      (calcitriol) therapies on parathyroid hormone (PTH) secretion were compared in 10
      hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT). These
      patients were randomized to receive either IVC or ORC therapy for 12 weeks, both
      followed by a 12-week washout period. After the washout, the patients who
      received IVC then switched to ORC therapy for another 12 weeks, and the patients
      who received ORC switched to IVC therapy. The mean dose of IVC was 2.45 +/- 0.30
      micrograms/dialysis session (approximately equal to 1.05 micrograms/day) and that
      of ORC was 0.69 +/- 0.07 micrograms/day. A significant reduction in serum levels
      of intact PTH was observed after 8 weeks and that of C-PTH after 10 weeks of ORC
      therapy, but both fell after 6 weeks of IVC treatment. There was a concomitant
      reduction in serum alkaline phosphatase (AP), but it became significant 4 weeks
      later than in intact PTH. The maximal reductions of serum levels of intact PTH, C
      PTH and AP were 74.28, 64.91, 41.97%, respectively, after IVC, and 31.57, 24.39,
      22.50%, respectively, after ORC therapy. Serum calcium rose faster during ORC
      treatment. There were no significant changes in serum levels of phosphorus,
      magnesium, and albumin throughout the treatment period. We conclude that both IVC
      or ORC treatments result in a significant decrement in blood levels of PTH in
      chronic HD patients with SHPT. However, this PTH-suppressive effect is more
      pronounced with IVC therapy, and cannot be totally explained by either the higher
      dose or elevated serum calcium.

PMID- 7816009
TI  - [Gaudent: the alloy that has opened new roads to dentistry].

PMID- 7816010
TI  - [The effects of ultramicronized synthetic hydroxyapatite on the etched enamel. An
      in-vitro study with computerized analysis].
AB  - The authors studied in vitro effects produced by etching (37% H3PO4) 80 microns
      thick teeth sections and the following application of H.A.u.m (Apagen). The
      changes of the superficial and lower layers were investigated by gray level
      alterations of section images. The changes were investigated by using a
      computerized image analysis system, by pseudocolors, standard deviation of gray
      levels and by calculating the surface rate affected by significative alteration.
      Etching application increased extension of high gray level zones. Pseudocolors
      showed 35 microns depth alterations. the evaluation of standard deviation means
      that major changes affected superficial layers; the evaluation of the extension
      of low gray levels zones showed a restoration of the pretreatment optical
      pattern. The results of this study demonstrate that H.A.u.m. (Apagen)
      applications are able to remineralize both superficial and lower layers of etched
      enamel.

PMID- 7816011
TI  - [Temporal muscle fatigue studied via muscle conduction velocity technics and
      spectral analysis of the electromyographic signal].
AB  - We examined 6 normal volunteers (3 males and 3 females, age 26-30). They were
      requested to clench as hard as they could until they felt pain. The experiment
      was repeated one hour later. Emg was recorded during the fatiguing exercise and
      the recovery period. We couldn't determine the muscle conduction velocity,
      probably because of the anatomy of the temporal muscle. The mean of the power
      spectrum showed wide variability and proved unsuitable for clinical applications,
      both for diagnosis and follow-up.

PMID- 7816012
TI  - [An in-vitro study of the antimicrobial activity of copper and zinc salts on pure
      and mixed microbial cultures].
AB  - The authors evaluated the in vitro antimicrobial activity of some copper and zinc
      salts. The results showed high antimicrobial activity of copper salts versus S.
      mutans and versus the bacterial association tested in this study.

PMID- 7816013
TI  - [An experimental clinical evaluation of the influence of the blood circulation on
      the parapulpal thermal levels].
AB  - The aim of this study is the evaluation of pulpal blood flow effect on the
      thermal levels measured at the pulpodentin junction in human anesthetized
      premolars. The value have been recorded as discrepancies between peak
      temperatures caused by a thermal stimulus applied on the same tooth in two
      different conditions: with and without pulpal blood supply. Thermal stimuli
      ranged from 3 to 9 degrees C on a total of twelve teeth giving a mean peak
      difference of 1.3 degrees C. This result has been interpreted as the effect of
      thermal dissipation produced by pulpal blood flow. The small magnitude of the
      value suggests, however, that anesthetized pulp fails to protect itself from
      injurious heat by increasing pulpal blood flow.

PMID- 7816014
TI  - [Occlusal re-equilibrium in patients with the craniomandibular dysfunctional
      syndrome. The use of a functional plate].
AB  - To elaborate any protocol treatment it is vitally important to start therapy with
      the aim of resolving the etiological factor in order to avoid the risk of
      recidivation. For this purpose the stages which have led to the loss of
      functional equilibrium must be traced backwards. The most striking symptoms of
      this damage are represented by the altered occlusal ratios, but the
      etiopathogenesis must be sought not only in occlusal causes but, more often, in
      dysmorphic, postural or neuro-muscular causes. It is necessary to start working
      backwards having restored the spatial position of the jaw in all three
      dimensions. In order to achieve this for the past three years the authors have
      routinely used an occlusal plate that they have perfected in the treatment of the
      majority of patients with dysfunctional syndrome of the stomatognathic apparatus.
      Over 70% of approximately 600 cases referred to the authors during the same
      period were treated in this way. The choice of these cases was conditioned by the
      facial typology of patients. In fact, these patients were characterised by a
      facial typology which tended to be hypo-divergent. This provoked a condition of
      "mandibular imprisonment" with an occlusal ratio which locks the jaw in a
      retruded position. This condition is identified by the authors as the factor that
      triggers the syndrome not only in those patients in which it is clearly possible
      to diagnose occlusal diagnosis, but also in those cases in which the pathogenetic
      motive has a number of causes, for example, poor posture and cases of
      dysmorphosis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7816015
TI  - [An outpatient regimen for dental improvements in patients with valvular
      cardiopathies and oral anticoagulant therapy (a preliminary note)].
AB  - The purpose of this paper is to verify the level of confidence of a new approach
      to the management of patients with cardiovalvular prosthetic and oral treatment
      with anticoagulants during high level risk oral surgery procedures. The new
      protocol includes: interrupted oral anticoagulant treatment; ambulatory regimen
      instead of hospital regimen; special dentistry management. No hemorrhagic
      complications occurred in the study sample. This paper concludes with a review of
      the role of Quick test in the management of patients with cardiac prostheses.

PMID- 7816016
TI  - Cowden's syndrome: a case report with clinical, histopathologic and immunological
      studies.
AB  - Cowden's syndrome is a rare autosomal dominant condition characterised by
      multiple hamartomas of the gastrointestinal tract and cancer of the breast and
      thyroid. We present a patient with multiple papillomatous lesions of the hard
      palate, facial papules, and a history of breast cancer and papillomas of the
      uterine cavity. We also report the results of light and electron microscopy of
      the palatal lesions and immunological studies of patient's T-lymphocyte function.

PMID- 7816017
TI  - [Benign pemphigoid of the mucous membranes: the clinical and histopathological
      aspects in 20 patients].
AB  - Benign mucous membrane pemphigoid is an autoimmune vesiculo-bullous disease which
      affects the oral mucosa. The purpose of this study is to report the clinical and
      pathological features of 20 patients with benign mucous membrane pemphigoid. Four
      patients were men and 16 female with a mean age of 58 years. The ratio of male to
      female was 1:4. Seventy percent of patients showed gingival involvement. Other
      locations were buccal mucosa, palate and floor of the mouth. The majority of
      patients had ulcers covered by pseudomembranes, complained of pain and burning
      and 40% reported bleeding gums. Nikolsky's sign was observed in 60% of cases. In
      all cases microscopic features of benign mucous membrane pemphigoid showed a
      separation of epithelium from the connective tissue along the basement membrane
      (sub-epithelial bulla).

PMID- 7816018
TI  - [Gingival overgrowth in patients under cyclosporin-A treatment. A clinical
      study].
AB  - The aim of the present study was to investigate possible background factors
      causing gingival overgrowth (GO) among transplant patients treated with
      cyclosporine-A (Cy-A). Nineteen subjects were evaluated with regard to Cy-A
      therapy including: whole blood concentration, oral dosage, duration of therapy,
      cumulative exposure factor. Periodontal condition was assessed using Plaque
      Index, probing depth and probing attachment level. GO was assessed on plaster
      study models by a semiquantitative method. The occurrence of GO was 88%, with a
      total 35.9% of gingival sites presenting overgrowth. Statistical analysis showed
      no correlation between GO score on one hand, oral dosage, exposure factor and
      plaque score on the other. ANOVA revealed a significant relationship between GO
      score and percentage of affected sites.

PMID- 7816019
TI  - Physical mapping of the 5S ribosomal RNA genes on rice chromosome 11.
AB  - One 5S ribosomal RNA gene (5S rDNA) locus was localized on chromosome 11 of
      japonica rice by in situ hybridization. The biotinylated DNA probe used was
      prepared by direct cloning and direct labeling methods, and the locus was
      localized to the proximal region of the short arm of chromosome 11 (11p1.1) by
      imaging methods. The distance between the signal site and the centromere is 4.0
      arbitrary units, where the total length of the short arm is 43.3 units. The
      5SrDNA locus physically identified and mapped in rice was designated as 5SRrn.
      The position of the 5S rDNA locus reported here differs from that in indica rice;
      possible reasons for this difference are discussed. DNA sequences of 5S rDNA are
      also reported.

PMID- 7816020
TI  - A Lactuca universal hybridizer, and its use in creation of fertile interspecific
      somatic hybrids.
AB  - A Lactuca sativa cv. Ardente line heterozygous for a gene encoding resistance to
      kanamycin, a positive and dominant trait, was crossed with cv. Girelle, which is
      heterozygous for a recessive albinism marker. The resulting seeds yielded 25%
      albino seedlings, of which 50% were also resistant to kanamycin. Such plantlets
      (KR, a) grown in vitro were used for preparation of universal hybridizer
      protoplasts, since green buds that can develop on kanamycin containing-medium
      should result from fusion with any wild-type protoplast. To test the
      practicability of this selection scheme, we fused L. sativa KR, a protoplasts
      with protoplasts derived from various wild Lactuca as well as various other
      related species. Protoplast-derived cell colonies were selected for resistance to
      kanamycin at the regeneration stage. Green buds were regenerated after fusion
      with protoplasts of L. tatarica and of L. perennis. So far, 9 interspecific
      hybrid plants have been characterized morphologically. In addition, random
      amplified polymorphic DNA (RAPD) analysis with selected primers confirmed that
      these plants are indeed interspecific hybrids. Some plants are female-fertile and
      production of backcross progenies with L. sativa is in progress. Since many
      desirable traits such as resistances to viruses, bacteria and fungi (Bremia
      lactucae) have been characterized in wild Lactuca species, the use of somatic
      hybridization in breeding programmes now appears a practical possibility.

PMID- 7816021
TI  - Allelic divergence in the human insulin gene provides evidence for intragenic
      recombination events in the non-coding regions: evidence for existence of new
      alleles.
AB  - Intragenic polymorphism of the human insulin gene (INS) was investigated in
      Korean subjects. The 1.9 kb INS sequence, including the 5' to 3' flanking
      regions, was amplified using the polymerase chain reaction (PCR), and analyzed by
      direct sequencing. All nucleotide sequences in the coding regions were the same
      as INS sequences previously reported, and four nucleotides, at positions +216,
      +1045, +1367, and +1380 in the non-coding regions, were found to be polymorphic.
      In addition to the previously identified polymorphic alleles alpha 1 (A-C-C-C)
      and beta 1 (T-G-T-A), new nucleotide arrangements were also identified and
      designated alpha 4 (A-C-C-A), alpha 5 (A-G-C-C), alpha 6 (A-C-T-C), and beta 2 (T
      C-C-C). It was concluded that the new alleles may originate by intragenic
      recombination within INS during chromosomal crossing-over between the alpha 1 and
      beta 1 alleles. The allele alpha 1 was the predominant form in our sample; the
      new variant alleles, as well as allele beta 1, appeared to be much less frequent
      in INSs genes of the Korean subjects studied. Furthermore, the new alleles were
      detected only in heterozygous form. These results suggest that intragenic
      recombination can account for allelic divergence in INS.

PMID- 7816022
TI  - Expression of Drosophila melanogaster F elements in vivo.
AB  - Drosophila melanogaster F elements are mobile, oligo(A)-terminated DNA sequences
      that probably propagate by the retrotranscription of RNA intermediates.
      Polyadenylated transcripts corresponding in size to full-length (4.7 kb) family
      members were detected in the Drosophila melanogaster Canton-S strain from 2nd
      larval instar to the adult stage. RNA accumulation reached a maximum in pupae. In
      the adult, F elements are transcribed in both sexes. F expression is directed in
      vivo by the intragenic promoter (Fin) located at the 5' end of F. Whole-mount
      hybridizations were carried out to define the site of synthesis of full-length
      transcripts found in the ovary. Selective RNA accumulation was not detected in
      the cytoplasm of any specific cell type. Stained nuclear dots were observed in
      nurse cells from stage 2-3 to the end of oogenesis. RNase treatment of egg
      chambers prior to the addition of the probe led to disappearance of the nuclear
      dots and appearance of a cytoplasmic hybridization signal suggesting leakage of
      nuclear transcripts. Transgenic lines harbouring the chloramphenicol
      acetyltransferase (CAT) gene under the control of the Fin promoter were obtained.
      In independent lines, CAT enzyme levels mirror the ontogenetic profile of F
      expression drawn from Northern RNA blotting data. An antisense promoter (Fout)
      that is located downstream from the Fin promoter and transcribe too bords the 5'
      end of F seems to be constitutively expressed in the fly.

PMID- 7816023
TI  - Sequencing and analysis of the cos region of the lactococcal bacteriophage c2.
AB  - The cohesive termini of the DNA genome of the lactococcal bacteriophage c2 were
      directly sequenced and appeared to be complementary, non-symmetrical, 9
      nucleotide single-stranded, 3' extended DNAs, with the following sequence: 5'
      GTTAGGCTT-3' 3'-CAATCCGAA-5'. DNA located on either side of the cohesive ends was
      sequenced and several repeats and a region with the potential for a DNA bend were
      found. Previously sequenced cos regions of 13 other bacteriophages were also
      examined for similar sequence features. All of the bacteriophages from gram
      positive hosts had 3' extended DNA termini, in contrast to the bacteriophages
      from gram-negative hosts, which had 5' extended DNA termini. All bacteriophages
      had a region of dyad symmetry close to the cohesive termini. A 7.3 kb DNA
      fragment of the c2 genome containing the cos sequences was cloned; transduction
      experiments demonstrated that these cloned sequences could act as a substrate for
      packaging enzymes of phage c2.

PMID- 7816024
TI  - Two subclasses of guanine exchange factor (GEF) domains revealed by comparison of
      activities of chimeric genes constructed from CDC25, SDC25 and BUD5 in
      Saccharomyces cerevisiae.
AB  - Guanine Exchange Factor (GEF) activity for Ras proteins has been associated with
      a conserved domain in Cdc25p, Sdc25p in Saccharomyces cerevisiae and several
      other proteins recently found in other eukaryotes. We have assessed the structure
      function relationships between three different members of this family in S.
      cerevisiae, Cdc25p, Sdc25p and Bud5p. Cdc25p controls the Ras pathway, whereas
      Bud5p controls bud site localization. We demonstrate that the GEF domain of
      Sdc25p is closely related to that of Cdc25p. We first constructed a
      thermosensitive allele of SDC25 by specifically altering amino acid positions
      known to be changed in the cdc25-1 mutation. Secondly, we constructed three
      chimeric genes from CDC25 and SDC25, the products of which are as active in the
      Ras pathway as are the wild-type proteins. In contrast, similar chimeras made
      between CDC25 and BUD5 lead to proteins that are inactive both in the Ras and
      budding control pathways. This difference in the ability of chimeric proteins to
      retain activity allows us to define two subclasses of structurally different
      GEFs: Cdc25p and Sdc25p are Ras-specific GEFs, and Bud5p is a putative GEF for
      the Rsr1/Bud1 Rap-like protein.

PMID- 7816025
TI  - Structural characterization and promoter activity analysis of the gamma-kafirin
      gene from sorghum.
AB  - A genomic clone encoding the gamma-kafirin gene from sorghum was isolated and
      sequenced. A 2938 bp sequenced fragment includes an intronless open reading frame
      of 636 nucleotides encoding a putative polypeptide of 212 amino acids. Comparison
      of the deduced amino acid sequence of gamma-kafirin with the published sequences
      of gamma-prolamins of maize, and Coix revealed highly conserved domains. The N
      terminal region of these proteins contains the conserved hexapeptide PPPVHL,
      which is repeated eight times in gamma-zein, four times in gamma-kafirin and
      three times in gamma-coixin. The number of PPPVHL repeats accounts predominantly
      for the differences in the molecular weights of gamma-prolamins. Several putative
      regulatory sequences common to the gamma-kafirin and gamma-zein genes were
      identified in both the 5' and the 3' flanking regions. Putative GCN4-like
      regulatory sequences were found at positions -192 and -476 in the 5' flanking
      region of gamma-kafirin. In the 3' noncoding region, three putative
      polyadenylation signals, two AATAAT and one AATGAA, were found at positions +658,
      +716, and +785, respectively. In order to investigate the role of the putative
      GCN4-like motifs and other possible cis-acting element(s) of the gamma-kafirin
      promoter, a series of deleted and chimeric promoter constructs were introduced
      into maize, Coix and sorghum tissues by particle bombardment. Histochemical
      analysis of beta-glucuronidase (GUS) activity in different tissues indicated that
      the element(s) responsible for tissue specificity is probably located in the 285
      bp proximal region of the promoter, while the remaining promoter sequence seems
      to carry the element(s) responsible for the quantitative response.

PMID- 7816026
TI  - Comparative analysis of microsatellite DNA polymorphism in landraces and
      cultivars of rice.
AB  - Genetic polymorphisms of ten microsatellite DNA loci were examined among 238
      accessions of landraces and cultivars that represent a significant portion of the
      distribution range for both indica and japonica groups of cultivated rice. In
      all, 93 alleles were identified with these ten markers. The number of alleles
      varied from a low of 3 or 4 at each of four loci, to an intermediate value of 9
      14 at five loci, and to an extraordinarily high 25 at one locus. The numbers of
      alleles per locus are much larger than those detected using other types of
      markers. The number of alleles detected at a locus is significantly correlated
      with the number of simple sequence repeats in the targeted microsatellite DNA.
      Indica rice has about 14% more alleles than japonica rice, and such allele number
      differences are more pronounced in landraces than in cultivars. The indica
      japonica differentiation component accounted for about 10% of the diversity in
      the total sample, and twice as much differentiation was detected in cultivars as
      in landraces. About two-thirds as many alleles were observed in cultivars as in
      landraces; another two-thirds of the alleles in the cultivar group were found in
      modern elite cultivars or parents of hybrid rice. The majority of the simple
      sequence repeat (SSR) alleles that were present in high or intermediate
      frequencies in landraces ultimately survived into modern elite cultivars and
      hybrids. The greater resolving power and the efficient production of massive
      amounts of SSR data may be particularly useful for germplasm assessment and
      evolutionary studies of crop plants.

PMID- 7816027
TI  - Isolation of an osmotic stress- and abscisic acid-induced gene encoding an acidic
      endochitinase from Lycopersicon chilense.
AB  - We have identified one osmotic stress- and abscisic acid-responsive member of the
      endochitinase (EC 3.2.1.14) gene family from leaves of drought-stressed
      Lycopersicon chilense plants, a natural inhabitant of extremely arid regions in
      South America. The 966-bp full-length cDNA (designated pcht28) encodes an acidic
      chitinase precursor with an amino-terminal signal peptide. The mature protein is
      predicted to have 229 amino acid residues with a relative molecular mass of
      24,943 and pI value of 6.2. Sequence analysis revealed that pcht28 has a high
      degree of homology with class II chitinases (EC 3.2.1.14) from tomato and
      tobacco. Expression of the pcht28 protein in Escherichia coli verified that it is
      indeed a chitinase. Northern blot analysis indicated that this gene has evolved a
      different pattern of expression from that of other family members reported thus
      far. It is highly induced by both osmotic stress and the plant hormone abscisic
      acid. Southern blot analysis of genomic DNA suggested that the pcht28-related
      genes may form a small multigene family in this species. The efficiency of
      induction of the gene by drought stress, in leaves and stems, is significantly
      higher in L. chilense than in the cultivated tomato. It is speculated that,
      besides its general defensive function, the pcht28-encoded chitinase may play a
      particular role in plant development or in protecting plants from pathogen attack
      during water stress.

PMID- 7816028
TI  - Identification and characterization of two functional domains of the hemolysin
      translocator protein HlyD.
AB  - Secretion of Escherichia coli hemolysin is mediated by a sec-independent pathway
      which requires the products of at least three genes, hlyB, hlyD and tolC. Two
      regions of HlyD were studied. The first region (region A), consisting of the 33
      amino acid, C-terminal part of the HlyD protein, is predicted to form a potential
      helix-loop-helix structure. This sequence is conserved among HlyD analogues of
      similar transport systems of other bacterial species. Using site-directed
      mutagenesis, we showed that the amino acids Leu475, Glu477 and Arg478 of this
      region are essential for HlyD function. The last amino acid of HlyD, Arg478, is
      possibly involved in the release of the HlyA protein, since cells bearing a hlyD
      gene mutant at this position produce similar amounts of HlyA to the wild-type
      strain, but most of the protein remains cell-associated. Competition experiments
      between wild-type and mutant HlyD proteins indicate that region A interacts
      directly with a component of the secretion apparatus. The second region of HlyD
      (region B), located between amino acids Leu127 and Leu170, is highly homologous
      to the otherwise unrelated outer membrane protein TolC. Deletion of this region
      abolishes secretion of hemolysin. This sequence of HlyD also seems to interact
      with a component of the hemolysin secretion machinery since a hybrid HlyD protein
      carrying the corresponding TolC sequence, although inactive in the transport of
      HlyA, is able to displace wild-type HlyD from the secretion apparatus.

PMID- 7816029
TI  - Toxicity of a heterologous leucyl-tRNA (anticodon CAG) in the pathogen Candida
      albicans: in vivo evidence for non-standard decoding of CUG codons.
AB  - Plasmids containing derivatives of the Saccharomyces cerevisiae leucyl-tRNA
      (tRNA(3Leu)) gene that vary in anticodon sequence were constructed and
      transformed into the pathogen Candida albicans and S. cerevisiae. C. albicans
      could readily be transformed with plasmids encoding leucyl-tRNA genes with the
      anticodons CAA and UAA (recognizing the codons UUG and UUA) and expression of the
      heterologous tRNALeu could be demonstrated by Northern RNA blotting. In contrast,
      no transformants were obtained if the anticodons were UAG (codons recognized CUN,
      UUR) and CAG (codon CUG), indicating that the insertion of leucine at CUG codons
      is toxic for C. albicans. All tRNALeu-encoding plasmids transformed S. cerevisiae
      with equally high efficiencies. These results provide in vivo evidence that non
      standard decoding of CUG codons is essential for the viability of C. albicans.

PMID- 7816030
TI  - Effect of mutations in the -10 region of the phoE promoter in Escherichia coli on
      regulation of gene expression.
AB  - The phoE promoter region in Escherichia coli contains a -10 region, typical of
      sigma 70-dependent promoters and, instead of a normal -35 region, a so-called pho
      box, to which the transcriptional activator phospho-PhoB binds under low
      phosphate conditions. A second pho box is present upstream of the first one and
      is required for full expression of phoE during phosphate starvation. To determine
      whether the lack of expression under high phosphate conditions is due solely to
      the absence of a genuine -35 box, the -10 region was further optimized towards
      the consensus -10 sequence and promoter activity was measured using alkaline
      phosphatase as a reporter. The mutations resulted in a drastic increment in the
      basal level of expression under high phosphate conditions, indicating that the
      deviations from consensus in the -10 region also play a role in determining the
      poor expression of the wild-type promoter under these conditions. The expression
      under high phosphate conditions was partly dependent on the presence of the phoB
      gene, showing that a small amount of active PhoB must be present under these
      circumstances. During phosphate starvation, the activity of the mutant promoters
      was further induced. The upstream pho box was not required for full expression
      from the mutant promoters under these conditions. Apparently, the wild-type phoE
      promoter is carefully balanced by deviations from the optimal Pribnow box
      sequence that reduce expression under high phosphate conditions and by the
      presence of several copies of the pho box, which enhance expression under
      phosphate starvation.

PMID- 7816031
TI  - Increase in incidence of chromosome instability and non-conservative
      recombination between repeats in Saccharomyces cerevisiae hpr1 delta strains.
AB  - Null hpr1 delta strains show a large increase (up to 2000-fold) over wild type in
      the frequency of occurrence of deletions between direct repeats on three
      different chromosomes. However, we show that hpr1 delta mutations have little or
      no effect on reciprocal exchange, gene conversion or unequal sister chromatid
      exchange, as determined using intrachromosomal, interchromosomal and plasmid
      chromosome assay systems. A novel intrachromosomal recombination system has
      allowed us to determine that over 95% of deletions in hpr1 delta strains do not
      occur by reciprocal exchange. On the other hand, hpr1 delta strains show
      chromosome loss frequencies of up to 100 times the wild-type level. Our results
      suggest that yeast cells have a very efficient non-conservative recombination
      mechanism, dependent on RAD1 and RAD52, that causes deletions between direct DNA
      repeats, and this mechanism is strongly stimulated in hpr1 delta strains. The
      results indicate that the Hpr1 protein is required for stability of DNA repeats
      and chromosomes. We propose that in the absence of the Hpr1 protein the cell
      destabilizes the genome by allowing the initiation of events that lead to
      deletions of sequences between repeats, and to chromosome instability. We discuss
      the roles that proteins such as Hpr1 have in maintaining direct repeats and in
      preventing non-conservative recombination and consider the importance of these
      functions for chromosome stability.

PMID- 7816032
TI  - The mitochondrial processing peptidase from potato: a self-processing enzyme
      encoded by two differentially expressed genes.
AB  - Cytochrome c reductase from potato is a bifunctional protein complex located in
      the inner mitochondrial membrane, which is involved in respiratory electron
      transport and processing of mitochondrial precursor proteins. The three largest
      subunits of the complex share the highest degree of sequence identity with the
      alpha- and beta-subunits of the soluble processing peptidase (MPP) from fungi and
      mammals. Evidence is provided that another substoichiometric polypeptide of the
      cytochrome c reductase complex resembles the alpha-subunit of MPP. A cDNA clone
      corresponding to the second alpha-MPP protein (alpha-II MPP) encodes a
      polypeptide of 504 amino acids which is 84% identical to alpha-I MPP. The two
      different alpha-MPP polypeptides have similar sizes on SDS-polyacrylamide gels
      but can be distinguished with an antibody raised against a decapeptide that is
      specific for alpha-II MPP. The presequences of both alpha-subunits of MPP are
      proteolytically removed by the integrated processing enzyme complex indicating
      that it acts on the targeting signals of its own precursor proteins. Gene
      specific oligonucleotides reveal that the genes encoding alpha-subunit I and
      alpha-subunit II of MPP are differentially expressed in all tissues analysed but
      the transcript levels do not vary between tissues.

PMID- 7816034
TI  - The nucleoid-associated DNA-binding protein H-NS is required for the efficient
      adaptation of Escherichia coli K-12 to a cold environment.
AB  - The hns gene is a member of the cold-shock regulon, indicating that the nucleoid
      associated, DNA-binding protein H-NS plays an important role in the adaptation of
      Escherichia coli to low temperatures. We show here that the ability to cope
      efficiently with a cold environment (12 degrees C and 25 degrees C) is strongly
      impaired in E. coli strains carrying hns mutations. Growth inhibition is much
      more pronounced in strains carrying the hns-206 allele (an ampicillin resistance
      cassette inserted after codon 37) than in those carrying the hns-205 mutation (a
      Tn10 insertion located in codon 93). A protein fragment (H-NS*) is synthesized in
      strains carrying the hns-205::Tn10 mutation, suggesting that this truncated
      polypeptide is partially functional in the cold adaptation process. Analysis of
      the growth properties of strains harbouring four different low-copy-number
      plasmid-encoded hns' genes that result in the production of C-terminally
      truncated H-NS proteins supports this proposal. H-NS* proteins composed of 133,
      117 or 94 amino-terminal amino acids partially complemented the severe cold
      sensitive growth phenotype of the hns-206 mutant. In contrast, synthesis of a
      truncated H-NS protein with only 75 amino-terminal amino acids was insufficient
      to restore growth at low temperature.

PMID- 7816033
TI  - Molecular characterization of a novel tobacco pathogenesis-related (PR) protein:
      a new plant chitinase/lysozyme.
AB  - A new PR (pathogenesis-related) protein was isolated from tobacco leaves
      (Nicotiana tabacum cv. Samsun NN), reacting hypersensitively to tobacco mosaic
      virus (TMV), by zinc chelate chromatography and was therefore named Pz. Its
      reactivity toward several lectins indicated the presence of bound sugar residues.
      From the amino acid sequence of tryptic peptides, Oligonucleotide primers were
      derived which allowed the synthesis of Pz cDNA by PCR. Using this cDNA as probe,
      near full-length clones were isolated from a library made from poly(A)+ RNA
      purified from TMV-infected leaves. Sequence analysis revealed similarities with
      chitinases/lysozymes of various origins and the purified protein was, indeed,
      shown to hydrolyse different N-acetylglucosamine-containing substrates.
      Comparison of peptide and cDNA sequences indicated that Pz protein is synthesized
      as a pre-pro-protein, a seven-amino acid C-terminal peptide probably being
      involved in the vacuolar targeting of the protein. Pz mRNA and protein were
      demonstrated to accumulate strongly in TMV-infected tobacco leaves. Pz
      transcripts were also found in various tissues of healthy plants, indicating that
      Pz gene expression is developmentally regulated.

PMID- 7816035
TI  - Identification of non-catalytic conserved regions in xylanases encoded by the
      xynB and xynD genes of the cellulolytic rumen anaerobe Ruminococcus flavefaciens.
AB  - xynB is one of at least four genes from the cellulolytic rumen anaerobe
      Ruminococcus flavefaciens 17 that encode xylanase activity. The xynB gene is
      predicted to encode a 781-amino acid product starting with a signal peptide,
      followed by an amino-terminal xylanase domain which is identical at 89% and 78%
      of residues, respectively, to the amino-terminal xylanase domains of the
      bifunctional XynD and XynA enzymes from the same organism. Two separate regions
      within the carboxy-terminal 537 amino acids of XynB also show close similarities
      with domain B of XynD. These regions show no significant homology with cellulose-
      or xylan-binding domains from other species, or with any other sequences, and
      their functions are unknown. In addition a 30 to 32-residue threonine-rich region
      is present in both XynD and XynB. Codon usage shows a consistent pattern of bias
      in the three xylanase genes from R. flavefaciens that have been sequenced.

PMID- 7816036
TI  - PET1402, a nuclear gene required for proteolytic processing of cytochrome oxidase
      subunit 2 in yeast.
AB  - The nuclear mutation pet ts1402 prevents proteolytic processing of the precursor
      of cytochrome oxidase subunit 2 (cox2) in Saccharomyces cerevisiae. The
      structural gene PET1402 was isolated by genetic complementation of the
      temperature-sensitive mutation. DNA sequence analysis identified a 1206-bp open
      reading frame, which is located 215 bp upstream of the PET122 gene. The DNA
      sequence of PET1402 predicts a hydrophobic, integral membrane protein with four
      transmembrane segments and a typical mitochondrial targeting sequence. Weak
      sequence similarity was found to two bacterial proteins of unknown function.
      Haploid cells containing a null allelle of PET1402 are respiratory deficient.

PMID- 7816037
TI  - MucAB but not UmuDC proteins enhance -2 frameshift mutagenesis induced by N-2
      acetylaminofluorene at alternating GC sequences.
AB  - N-2-acetylaminofluorene has been shown efficiently to induce both -1 and -2
      frameshift mutations in Escherichia coli as well as in mammalian cells. In E.
      coli, the genetic characteristics of -1 and -2 frameshift mutations were found to
      be distinct. The -1 frameshift mutation pathway occurs at monotonous runs of G
      residues (i.e. GGG-->GG). This pathway exhibits the same genetic requirements as
      UV light-induced base substitution mutagenesis. Indeed, optimal mutagenesis
      requires the expression of both UmuDC and the activated form of RecA. The -2
      frameshift mutation pathway operates at short alternating GpC sequences, such as
      the NarI sequence (i.e. GGCGCC-->GGCC). In contrast to the -1 frameshift mutation
      pathway, optimal induction does not require the UmuDC and RecA proteins. This
      pathway involves a LexA-repressed function tentatively called Npf (for NarI
      processing factor). In this paper, we show that MucAB efficiently stimulates the 
      2 frameshift mutation pathway. However, unlike the Npf pathway, MucAB-mediated
      stimulation requires expression of the RecA protein.

PMID- 7816038
TI  - Evolution of the C4 phosphoenolpyruvate carboxylase promoter of the C4 dicot
      Flaveria trinervia: an expression analysis in the C3 plant tobacco.
AB  - The key enzymes of photosynthetic carbon assimilation in C4 plants have evolved
      from C3 isoforms which were present in the C3 ancestral species. We are
      interested in the molecular changes responsible for the novel expression pattern
      of C4 genes and are focussing on phosphoenolpyruvate carboxylase (PEPCase) of the
      genus Flaveria. The C4 isoform of PEPCase in the C4 plant F. trinervia is encoded
      by the ppcA subgroup of the PEPcase gene family and is abundantly expressed in
      the mesophyll cells of leaves. The orthologous ppcA genes of the C3 plant F.
      pringlei are only weakly expressed and their transcripts do not accumulate in a
      leaf-specific manner but, rather, are present in all plant organs. To answer the
      question whether the differences in the expression levels of the ppcA genes from
      F. pringlei and F. trinervia are caused by changes in the 5' upstream regions of
      the genes or by C4-specific trans-regulatory factors, varying parts of the 5'
      flanking region of the ppcA1 genes of both species were fused to the beta
      glucuronidase (GUS) gene and inserted in the tobacco genome. GUS expression
      analysis of transgenic plants revealed that the level of expression of the
      Flaveria ppcA1 genes are recapitulated in the heterologous C3 plant tobacco.
      Hence, the 5' upstream region of the ppcA1 gene of F. trinervia contains
      regulatory cis-elements that are responsible for the C4-specific, abundant
      expression of this gene. These sequences are located upstream of position -500
      relative to the transcription initiation site.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7816039
TI  - Recombination between repeats in Escherichia coli by a recA-independent,
      proximity-sensitive mechanism.
AB  - We have examined the influence of proximity on the efficiency of recombination
      between repeated DNA sequences in Escherichia coli. Our experiments have employed
      a plasmid-based assay to detect deletions between direct repeats of 100 bp. The
      rate of deletion of the juxtaposed direct repeats was reasonably high at 6 x 10(
      5) per cell. A comparison of recA+ and recA mutant strains showed that these
      deletion events are primarily the result of recA-independent recombination at
      these homologous sequences. Random restriction fragments of yeast or E. coli
      genomic DNA were used to separate the two repeats. Deletion rates decreased over
      two orders of magnitude with increasing separation of up to 7 kb. There was a
      surprisingly strong effect of even short sequence separations, with insertions of
      a few hundred base pairs exhibiting 10-fold reductions of deletion rates. No
      effect of recA on the efficiency of deletion was observed at any distance between
      repeats.

PMID- 7816040
TI  - Positive and negative transcriptional regulation by the yeast GAL11 protein
      depends on the structure of the promoter and a combination of cis elements.
AB  - GAL11 was first identified as a gene required for full expression of some
      galactose-inducible genes that are activated by GAL4, and it was subsequently
      shown to be necessary for full expression of another set of genes activated by
      RAP1/GRF1/TUF. Genetic analysis suggests that GAL11 functions as a coactivator,
      mediating the interaction of sequence-specific activators with basal
      transcription factors. To test this hypothesis, we first tried to identify
      functional domains by deletion analysis and found that the 866-910 region is
      indispensable for function. Using reporters bearing various upstream activating
      sequences (UAS) and different core promoter structures, we show that the
      involvement of GAL11 in transcriptional activation varies with the target
      promoter and the particular combination of cis elements. Gel electrophoresis in
      the presence of chloroquine shows that GAL11 affects the chromatin structure of a
      circular plasmid. Based on these findings, the role of GAL11 in regulation of
      transcription, including an alteration in chromatin structure, is discussed.

PMID- 7816041
TI  - Oxygen sensitivity and metal ion-dependent transcriptional activation by NIFA
      protein from Rhizobium leguminosarum biovar trifolii.
AB  - The NIFA protein from Rhizobium leguminosarum biovar trifolii (R. trifolii)
      strain ANU843 lacks an N-terminal domain present in homologous NIFA proteins from
      other diazotrophs. The R. trifolii nifA gene product is unstable when expressed
      in Escherichia coli under both aerobic and microaerobic conditions. Stability is
      increased by fusion of additional amino acids to the N-terminus of the protein or
      by expression of nifA in sno mutant (presumed protease deficient) strains of E.
      coli. Transcriptional activation in vivo by R. trifolii NIFA decreases under
      aerobic growth conditions, or when cultures are depleted of metal ions. In sno
      mutant strains this decrease in activity reflects a loss of specific activity
      rather than proteolytic degradation, implying that R. trifolii NIFA requires
      metal ions for activity and is oxygen sensitive. The addition of 30 amino acids
      to the amino-terminus of R. trifoli NIFA results in an oxygen-tolerant protein,
      with metal ion-dependent activity. Metal ions are therefore not only required for
      oxygen sensing by R. trifolii NIFA but may play an additional role in determining
      NIFA structure or activity.

PMID- 7816042
TI  - Inactivation of SSM4, a new Saccharomyces cerevisiae gene, suppresses mRNA
      instability due to rna14 mutations.
AB  - Decay rates of mRNAs depend on many elements and among these, the role of the
      poly(A) tail is now well established. In the yeast Saccharomyces cerevisiae,
      thermosensitive mutations in two genes, RNA14 and RNA15, result in mRNAs having
      shorter poly(A) tails and reduced half-life. To identify other components
      interacting in the same process, we have used a genetic approach to isolate
      mutations that suppress the thermosensitivity of an rna14 mutant strain.
      Mutations in a single locus, named SSM4, not only suppress the cell growth
      phenotype but also the mRNA instability and extend the short mRNA poly(A) tails.
      The frequency of appearance and the recessive nature of these mutations suggested
      that the suppressor effect was probably due to a loss of function. We failed to
      clone the SSM4 gene directly by complementation, owing to its absence from gene
      banks; it later emerged that the gene is toxic to Escherichia coli, but we have
      nevertheless been able to clone the SSM4 sequence by Ty element transposition
      tagging. Disruption of the SSM4 gene does not affect cell viability and
      suppresses the rna14 mutant phenotypes. The protein encoded by the SSM4 gene has
      a calculated molecular mass of 151 kDa and does not contain any known motif or
      show homology with known proteins. The toxicity of the SSM4 gene in E. coli
      suggests that a direct biochemical activity is associated with the corresponding
      protein.

PMID- 7816043
TI  - ISL2, a new mobile genetic element in Lactobacillus helveticus.
AB  - Spontaneous, phenotypically stable mutations at the beta-galactosidase locus
      (lacL-lacM) in Lactobacillus helveticus were identified and analyzed. We found
      that a significant number of mutations were caused by integration of a new IS
      element, ISL2, into these lac genes. ISL2 is 858 bp long, flanked by 16-bp
      perfect inverted repeats and generates 3-bp target duplications upon insertion.
      It contains one open reading frame, which shows significant homology (40.1%
      identity) to the putative transposase of IS702 from Cyanobacterium calothrix.
      ISL2 is present in 4-21 copies in the L. helveticus genome, but it is not found
      in other lactic acid bacteria. Its divergence in copy number and genomic
      locations in different L. helveticus strains makes it useful as a tool for strain
      identification by genetic fingerprinting.

PMID- 7816044
TI  - Pot2, an inverted repeat transposon from the rice blast fungus Magnaporthe
      grisea.
AB  - We report the cloning and characterisation of Pot2, a putative transposable
      element from Magnaporthe grisea. The element is 1857 bp in size, has 43-bp
      perfect terminal inverted repeats (TIRs) and 16-bp direct repeats within the
      TIRs. A large open reading frame, potentially coding for a transposase-like
      protein, was identified. This putative protein coding region showed extensive
      identity to that of Fot1, a transposable element from another phytopathogenic
      fungus, Fusarium oxysporum. Pot2, like the transposable elements Tc1 and Mariner
      of Caenorhabditis elegans and Drosophila, respectively, duplicates the
      dinucleotide TA at the target insertion site. Sequence analysis of DNA flanking
      12 Pot2 elements revealed similarity to the consensus insertion sequence of Tc1.
      Pot2 is present at a copy number of approximately 100 per haploid genome and
      represents one of the major repetitive DNAs shared by both rice and non-rice
      pathogens of M. grisea.

PMID- 7816045
TI  - A family of related sequences associated with (TTTAGGG)n repeats are located in
      the interstitial regions of wheat chromosomes.
AB  - A family of related sequences associated with (TTTAGGG)n repeats has been cloned
      from the wheat cultivar Chinese Spring. These sequences reveal a high level of
      polymorphism between wheat varieties when used as restriction fragment length
      polymorphism (RFLP) probes. Although this family of sequences contains motifs
      homologous to the repeats in the telomeres of wheat, they are located at
      interstitial sites on wheat chromosomes.

PMID- 7816046
TI  - In planta transformation of Arabidopsis thaliana.
AB  - Transformants of Arabidopsis thaliana can be generated without using tissue
      culture techniques by cutting primary and secondary inflorescence shoots at their
      bases and inoculating the wound sites with Agrobacterium tumefaciens suspensions.
      After three successive inoculations, treated plants are grown to maturity,
      harvested and the progeny screened for transformants on a selective medium. We
      have investigated the reproducibility and the overall efficiency of this simple
      in planta transformation procedure. In addition, we determined the T-DNA copy
      number and inheritance in the transformants and examined whether transformed
      progeny recovered from the same Agrobacterium-treated plant represent one or
      several independent transformation events. Our results indicate that in planta
      transformation is very reproducible and yields stably transformed seeds in 7-8
      weeks. Since it does not employ tissue culture, the in planta procedure may be
      particularly valuable for transformation of A. thaliana ecotypes and mutants
      recalcitrant to in vitro regeneration. The transformation frequency was variable
      and was not affected by lower growth temperature, shorter photoperiod or
      transformation vector. The majority of treated plants gave rise to only one
      transformant, but up to nine siblings were obtained from a single parental plant.
      Molecular analysis suggested that some of the siblings originated from a single
      transformed cell, while others were descended from multiple, independently
      transformed germ-line cells. More than 90% of the transformed progeny exhibited
      Mendelian segregation patterns of NPTII and GUS reporter genes. Of those, 60%
      contained one functional insert, 16% had two T-DNA inserts and 15% segregated for
      T-DNA inserts at more than two unlinked loci. The remaining transformants
      displayed non-Mendelian segregation ratios with a very high proportion of
      sensitive plants among the progeny.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7816047
TI  - Two distinct cis-acting elements are involved in light-dependent activation of
      the pea elip promoter.
AB  - Light activation of the pea (Pisum sativum) elip gene promoter was analysed in
      transgenic plants and in transiently transfected plant protoplasts. A series of
      promoter deletions fused to the gusA reporter was tested, and the results
      obtained by the two experimental approaches were in good agreement. We identified
      two nucleotide sequence elements involved in light-regulated expression of the
      elip gene. One element is similar to the GT1 binding site of the rbcS-3A gene,
      and the other resembles a G-box-like ACGT element. The region containing both
      elements was able to confer light responsiveness on a heterologous basic
      promoter. Electrophoretic mobility shift assays demonstrated that each element is
      specifically recognized by DNA-binding proteins present in nuclear extracts from
      pea seedlings. The G-box-like ACGT element is necessary but not sufficient for
      light inducibility, indicating that the two elements act together in confering
      light responsiveness.

PMID- 7816048
TI  - Organ-specific expression of highly divergent thionin variants that are distinct
      from the seed-specific crambin in the crucifer Crambe abyssinica.
AB  - Most thionins of higher plants are toxic to various bacteria, fungi, and animal
      and plant cells. The only known exception is the seed-specific thionin, crambin,
      of the crucifer Crambe abyssinica. Crambin has no net charge, is very hydrophobic
      and exhibits no toxicity. In the present work, the organization of the crambin
      precursor polypeptide was deduced from cD-NA sequences. The precursor shows a
      domain structure similar to that of the preproprotein of other thionins, which
      contains a signal peptide, a thionin domain and a C-terminal amino acid
      extension. Unlike the thionin precursors studied thus far, both the thionin
      domain and the C-terminal amino acid extension of the crambin precursor have no
      net charge and are hydrophobic, thus facilitating their interaction, by analogy
      to that proposed for the corresponding domains of other thionin precursors that
      have positive and negative charges. The existence of a large number of novel and
      highly variable thionin variants in Crambe abyssinica has been deduced from cDNA
      sequences that were amplified by the polymerase chain reaction (PCR) from RNA of
      seeds, leaves and cotyledons. While the deduced amino acid sequences of the
      thionin domains of most of these thionin precursor molecules are highly
      divergent, the two other domains are conserved. Most of the predicted thionin
      variants are positively charged. The presence of positively charged residues in
      the thionin domains consistently correlates with the presence of a negatively
      charged residue in the C-terminal amino acid extension of the various thionin
      precursors. The different thionin variants are encoded by distinct sets of genes
      and are expressed in an organ-specific manner.

PMID- 7816049
TI  - Gene density and organization in a small region of the Arabidopsis thaliana
      genome.
AB  - We have characterized a 6.4 kb genomic fragment from Arabidopsis thaliana ecotype
      Columbia overlapping the 5' end of the AKin10 gene which encodes a protein
      Ser/Thr kinase. Using, as probes, various restriction fragments located upstream
      of AKin10, two cDNA clones have been isolated from a cDNA library prepared from
      young shoot tissue. A comparison between the cDNA and the above genomic sequences
      allowed us to locate two novel genes, Atcys1 and Athyp1 (for Arabidopsis thaliana
      cystathionine gamma-synthase 1 and hypothetical protein 1). The coding sequences
      of both genes are interrupted by introns and the exons match the sequences of the
      corresponding cDNAs. Further analysis of the genomic fragment revealed the
      presence of an open reading frame (ORF) of 609 nucleotides situated between the
      two genes. Atcys1, Athyp1, AKin10 and the ORF are very close to each other and
      organized in the same polarity; hence, the intergenic regions probably contain,
      within less than 0.5 kb, all the regulatory elements necessary to govern
      initiation and termination of transcription. The deduced protein sequence of
      Atcys1 shows a high degree of similarity with the cystathionine gamma-synthase
      from Escherichia coli. The putative product of the Athyp1 gene contains seven
      hydrophobic regions flanked by hydrophilic domains, reminiscent of membrane
      spanning proteins. Southern blot hybridization experiments suggest the presence
      of one copy of Atcys1, Athyp1 and AKin10 per haploid genome, and Northern blot
      analysis demonstrates that the three genes are differentially expressed in roots,
      shoots and leaves.

PMID- 7816050
TI  - Calcium and smooth muscle contraction.
AB  - The fact that smooth muscle exists in almost every hollow organ and is involved
      in a large number of disease states has led to a vast increase in smooth muscle
      research, covering areas from testing response to antagonists and agonists to
      measuring the molecular force generated by a single actin filament. Yet, the
      exact mechanisms regulating contractile response of smooth muscle remain
      unsolved. Calcium has been a central player in mediating smooth muscle
      contraction through binding with calmodulin, although there is evidence showing
      that under special circumstances smooth muscle can contract without change in
      intracellular Ca2+. In addition to the major regulatory pathway of Ca(2+)
      calmodulin-myosin light chain kinase, there are other thin filament linked
      regulatory mechanisms in which Ca(2+)-calmodulin dependent phosphorylation of
      calponin and caldesmon may be involved. Ca2+ sensitivity of smooth muscle
      contraction may vary under different situations and this has recently been
      recognized as an important regulatory mechanism. Examples are protein kinase C
      (PKC) dependent phosphorylation of myosin light chain kinase which results in
      partial inhibition of contraction, and activation of myosin light chain
      phosphatase. There is new evidence showing that not only does Ca2+ regulate
      contraction by regulating the interaction of contractile proteins in smooth
      muscle, but also that shortening of smooth muscle itself reduces intracellular
      Ca2+ concentration, via a negative feedback.

PMID- 7816051
TI  - Renal handling of Ca2+ in diabetes.
AB  - Ca2+ transport in kidney has gained considerable attention in the recent past.
      Our laboratory has been involved in understanding the regulatory mechanisms
      underlying Ca2+ transport in the kidney across the renal basolateral membrane. We
      have shown that ANP, a cardiac hormone, mediates its biological functions by
      acting on its receptors in the kidney basolateral membrane. Furthermore, it has
      been established that ANP receptors are coupled with Ca2+ ATPase, the enzyme that
      participates in the vectorial translocation of Ca2+ from the tubular lumen to the
      plasma. It is possible that a defect in the ANP-receptor-effector system in
      diabetes (under certain conditions such as hypertension) may be associated with
      abnormal Ca2+ homeostasis and the development of nephropathy. Accordingly, future
      studies are needed to establish this hypothesis.

PMID- 7816052
TI  - Angiotensin II contractions in coronary artery. Nature of receptors and calcium
      pools.
AB  - Pig coronary artery rings denuded of endothelium contract to the vasoactive
      hormone angiotensin II (Ang II). The nature of Ang II receptors and their Ca(2+)
      pool utilization were examined for contraction of the artery rings and for
      increase in ultracellular [Ca2+] ([Ca2+]i) in smooth muscle cells cultured from
      them. Ang II contracted the arteries (EC50 = 7 +/- 4 nM) but with a lower maximal
      force (1.4 +/- 0.25 N/g tissue) than the contraction with 60 mM K+ (6.11 +/- 0.63
      N/g tissue). In the cultured cells it caused a transient increase in [Ca2+]i with
      an EC50 value of 11 +/- 4 nM. The cells bound Ang II with a dissociation constant
      (Kd) of 7 +/- 2 nM. Based on the effects of the Ang II antagonists saralasin,
      DuPont 753, dithiothreitol and PD123319, the Ang II receptors responsible for
      contraction, increase in [Ca2+]i and Ang II binding to coronary artery smooth
      muscle were of type AT1. The contraction to Ang II was abolished by EGTA but not
      by nitrendipine. The sarcoplasmic Ca2+ pump inhibitors cyclopiazonic acid (10
      microM CPA) and thapsigargin (1 microM) produced contractions of 4.35 +/- 0.73
      and 2.07 +/- 0.54 N/g, respectively. Ang II contractions in the control arteries
      were nearly abolished upon pretreatment with CPA and thapsigargin. CPA and
      thapsigargin induced contractions were abolished by exposure to EGTA for 1 h but
      short exposure of the cells to EGTA only modulated the CPA or thapsigargin
      induced increase in [Ca2+]i; Ang II induced increase in [Ca2+]i was not inhibited
      by 1 microM nitrendipine but was reduced significantly by a 30-60 sec exposure to
      EGTA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7816053
TI  - Signal transduction mechanism for the stimulation of the sarcolemmal Na(+)-Ca2+
      exchanger by insulin.
AB  - The signal transduction pathway for insulin-mediated activation of sarcolemmal
      Na(+)-Ca2+ exchange was examined. Insulin stimulated Na(+)-Ca2+ exchanger
      activity in a dose-dependent manner, with the EC50 being about 0.7 U/l. The
      insulin effect was blocked by the protein kinase inhibitor, staurosporine,
      indicating possible involvement of a protein kinase in insulin action. Also, the
      relationship between the insulin effect and activation of a G protein was
      examined by testing the effects of 5' guanylyl imidodiphosphate (Gpp(NH))p) on
      Na(+)-Ca2+ exchange in the presence and absence of insulin. When exchanger
      activity was assayed at a calcium concentration of 40 microM, insulin alone had
      no effect whereas ATP and Gpp(NH)p increased exchanger activity. However, insulin
      responsiveness was restored in vesicles preloaded with either ATP or Gpp(NH)p,
      suggesting that insulin may act through a combination of G protein coupling and
      protein phosphorylation to enhance Na(+)-Ca2+ exchanger activity. We conclude
      that calcium overload in the diabetic heart may involve a defect in acute
      activation of the exchanger by insulin.

PMID- 7816056
TI  - Calcium-supported calpain degradation rates for cardiac myofibrils in diabetes.
      Sulfhydryl and hydrophobic interactions.
AB  - OBJECTIVE: The purpose was to investigate the calcium required for calpain
      mediated degradation of selected cardiac myofibril proteins modified by diabetes,
      sulfhydryl (SH) and hydrophobic reagents. METHODS: After 20 weeks of
      streptozotocin-induced (55 mg.kg-1) diabetes, calcium sensitive calpain (1.5 U.ml
      1) degradation rates of purified cardiac myofibrillar proteins (1 mg.ml-1) were
      measured, in vitro, and compared to degradation rates for N-ethylmaleimide (NEM)
      and 2-p-toluidinylnapthalene-6-sulfonate (TNS) treated samples. RESULTS: Diabetes
      (blood glucose of 550 +/- 32 mg.dl-1) reduced the yield of purified myofibrillar
      protein with minimal change in fibril protein composition. Total SH group
      reactivities (nmol.mg-1.30min) were 220 +/- 21, 163 +/- 17 and 156 +/- 24 for
      control, diabetic and NEM-treated (0.5 mM) myofibrils (p < or = 0.05). Calpain
      degradation rates were faster for all diabetic and SH modified myofibrillar
      proteins (p < or = 0.05), with a 45 and 35% reduction in the pCa50 for a 37 kDa
      protein of diabetic and NEM-treated fibril complexes. For control myofibrils,
      both 100 and 200 uM TNS, reduced calpain degradation rates to a similar extent
      for all substrate proteins. In contrast, diabetic and NEM-treated samples showed
      a further reduction in calpain degradation rates with increasing TNS from 100 to
      200 uM. CONCLUSION: Our results support the hypothesis that in diabetes the
      calcium requirements for calpain degradation rates are reduced and dependent upon
      sulfhydryl group status and Ca(2+)-induced hydrophobic interactions, implicating
      a 37 kDa myofbillar-complexed protein.

PMID- 7816055
TI  - Role of regulatory proteins (troponin-tropomyosin) in pathologic states.
AB  - In vertebrate striated muscle, troponin-tropomyosin is responsible, in part, not
      only for transducing the effect of calcium on contractile protein activation, but
      also for inhibiting actin and myosin interaction when calcium is absent. The
      regulatory troponin (Tn) complex displays several molecular and calcium binding
      variations in cardiac muscles of different species and undergoes genetic changes
      with development and in various pathologic states. Extensive reviews on the role
      of tropomyosin (Tm) and Tn in the regulation of striated muscle contraction have
      been published describing the molecular mechanisms involved in contractile
      protein regulation. In our studies, we have found an increase in Mg2+ ATPase
      activity in cardiac myofibrils from dystrophic hamsters and in rats with chronic
      coronary artery narrowing. The abnormalities in myofibrillar ATPase activity from
      cardiomyopathic hamsters were largely corrected by recombining the preparations
      with a TnTm complex isolated from normal hamsters indicating that the TnTm may
      play a major role in altered myocardial function. We have also observed down
      regulation of Ca2+ Mg2+ ATPase of myofibrils from hypertrophic guinea pig hearts,
      myocardial infarcted rats and diabetic-hypertensive rat hearts. In myosin from
      diabetic rats, this abnormality was substantially corrected by adding troponin
      tropomyosin complex from control hearts. All of these disease models are
      associated with decreased ATPase activities of pure myosin and in the case of rat
      and hamster models, shifts of myosin heavy chain from alpha to beta predominate.
      In summary, there are three main troponin subunit components which might alter
      myofibrillar function however, very few direct links of molecular alterations in
      the regulatory proteins to physiologic and pathologic function have been
      demonstrated so far.

PMID- 7816058
TI  - Calreticulin: not just another calcium-binding protein.
AB  - In this paper we review some of the rapidly expanding information about
      calreticulin, a Ca(2+)-binding/storage protein of the endoplasmic reticulum. The
      emphasis is placed on the structure and function of calreticulin. We believe that
      calreticulin is a multifunctional Ca(2+)-binding protein and that distinct
      functional properties of the protein may be localized to each of the three
      structural domains of calreticulin. Most evidence indicates that calreticulin is
      a resident endoplasmic reticulum protein. However, it can also be found outside
      of the endoplasmic reticulum compartment, i.e. in the nuclear envelope, in the
      nucleus, in the cytotoxic granules in T-lymphocytes and in acrosomal vesicles of
      sperm cells. The evidence reviewed here clearly suggests that calreticulin has
      other functions in addition to its role as a Ca2+ storage protein in the
      endoplasmic reticulum.

PMID- 7816057
TI  - Sarcoplasmic reticulum calsequestrins: structural and functional properties.
AB  - Calsequestrin is the major Ca(2+)-binding protein localized in the terminal
      cisternae of the sarcoplasmic reticulum (SR) of skeletal and cardiac muscle
      cells. Calsequestrin has been purified and cloned from both skeletal and cardiac
      muscle in mammalian, amphibian, and avian species. Two different calsequestrin
      gene products namely cardiac and fast have been identified. Fast and cardiac
      calsequestrin isoforms have a highly acidic amino acid composition. The amino
      acid composition of the cardiac form is very similar to the skeletal form except
      for the carboxyl terminal region of the protein which possess variable length of
      acidic residues and two phosphorylation sites. Circular dichroism and NMR studies
      have shown that calsequestrin increases its alpha-helical content and the
      intrinsic fluorescence upon binding of Ca2+. Calsequestrin binds Ca2+ with high
      capacity and with moderate affinity and it functions as a Ca2+ storage protein in
      the lumen of the SR. Calsequestrin has been found to be associated with the Ca2+
      release channel protein complex of the SR through protein-protein interactions.
      The human and rabbit fast calsequestrin genes have been cloned. The fast gene is
      skeletal muscle specific and transcribed at different rates in fast and slow
      skeletal muscle but not in cardiac muscle. We have recently cloned the rabbit
      cardiac calsequestrin gene. Heart expresses exclusively the cardiac calsequestrin
      gene. This gene is also expressed in slow skeletal muscle. No change in
      calsequestrin mRNA expression has been detected in animal models of cardiac
      hypertrophy and in failing human heart.

PMID- 7816059
TI  - Calcium and calcium-binding proteins in the nucleus.
AB  - Calcium has long been known to play a role as a key cytoplasmic second messenger,
      but until relatively recently its possible involvement in nuclear signal
      transduction and the regulation of nuclear events has not been extensively
      studied. Evidence revealing the presence of transmembrane nuclear Ca2+ gradients
      and a variety of intranuclear Ca2+ binding proteins has fueled renewed interest
      in this key ion and its involvement in cell-cycle timing and division, gene
      expression, and protein activation. This review will offer an overview of the
      current state of knowledge and theory regarding calcium orchestration of nuclear
      functions and events and discuss possible future directions in this field of
      study.

PMID- 7816060
TI  - Nuclear Ca2+: physiological regulation and role in apoptosis.
AB  - The last decade has seen the rapid development of research investigating the
      molecular mechanisms whereby hormones, peptide growth factors and cytokines
      regulate cell metabolism, differentiation and proliferation. One general
      signalling mechanism used to transfer the information delivered by agonists into
      appropriate intracellular compartments involves the rapid Ca2+ redistribution
      throughout the cell, which results in transient elevations of the cytosolic free
      Ca2+ concentration. Ca2+ signals are required for a number of cellular processes
      including the activation of nuclear processes such as gene transcription and cell
      cycle events. The latter require that appropriate Ca2+ signals elicited in
      response to agonists be transduced across the nuclear envelope. It has generally
      been assumed that small molecules, metabolites and ions could freely diffuse
      across the nuclear envelope. Nevertheless several findings during the past few
      years have suggested that nuclear pore permeability can be regulated and that ion
      transport systems and ion-selective channels may exist on the nuclear membranes
      and regulate intranuclear processes. Intranuclear Ca2+ fluctuations can affect
      chromatin organization, induce gene expression and also activate cleavage of
      nuclear DNA by nucleases during programmed cell death or apoptosis. The possible
      mechanisms involved in nuclear Ca2+ transport and the control of nuclear Ca(2+)
      dependent enzymes in apoptosis is discussed below.

PMID- 7816054
TI  - Calmodulin and the regulation of smooth muscle contraction.
AB  - Calmodulin, the ubiquitous and multifunctional Ca(2+)-binding protein, mediates
      many of the regulatory effects of Ca2+, including the contractile state of smooth
      muscle. The principal function of calmodulin in smooth muscle is to activate
      crossbridge cycling and the development of force in response to a [Ca2+]i
      transient via the activation of myosin light-chain kinase and phosphorylation of
      myosin. A distinct calmodulin-dependent kinase, Ca2+/calmodulin-dependent protein
      kinase II, has been implicated in modulation of smooth-muscle contraction. This
      kinase phosphorylates myosin light-chain kinase, resulting in an increase in the
      calmodulin concentration required for half-maximal activation of myosin light
      chain kinase, and may account for desensitization of the contractile response to
      Ca2+. In addition, the thin filament-associated proteins, caldesmon and calponin,
      which inhibit the actin-activated MgATPase activity of smooth-muscle myosin (the
      cross-bridge cycling rate), appear to be regulated by calmodulin, either by the
      direct binding of Ca2+/calmodulin or indirectly by phosphorylation catalysed by
      Ca2+/calmodulin-dependent protein kinase II. Another level at which calmodulin
      can regulate smooth-muscle contraction involves proteins which control the
      movement of Ca2+ across the sarcolemmal and sarcoplasmic reticulum membranes and
      which are regulated by Ca2+/calmodulin, e.g. the sarcolemmal Ca2+ pump and the
      ryanodine receptor/Ca2+ release channel, and other proteins which indirectly
      regulate [Ca2+]i via cyclic nucleotide synthesis and breakdown, e.g. NO synthase
      and cyclic nucleotide phosphodiesterase. The interplay of such regulatory
      mechanisms provides the flexibility and adaptability required for the normal
      functioning of smooth-muscle tissues.

PMID- 7816062
TI  - Decline in semen quality among fertile men in Paris during the past 20 years.
AB  - BACKGROUND: Several studies have suggested a population-wide decline in the
      quality of semen over the past 50 years, but clear evidence for decreasing semen
      quality in recent decades is lacking. METHODS: From 1973 through 1992 we measured
      the volume of seminal fluid, the sperm concentration, and the percentages of
      motile and morphologically normal spermatozoa in 1351 healthy fertile men. The
      data on the semen samples were collected at one sperm bank in Paris. The data in
      each calendar year were analyzed as a function of the year of donation, the age
      of each patient, the year of birth, and the duration of sexual abstinence before
      semen collection. RESULTS: There was no change in semen volume during the study
      period. The mean concentration of sperm decreased by 2.1 percent per year, from
      89 x 10(6) per milliliter in 1973 to 60 x 10(6) per milliliter in 1992 (P <
      0.001). During the same period the percentages of motile and normal spermatozoa
      decreased by 0.6 percent and 0.5 percent per year, respectively (both P < 0.001).
      After adjustment in multiple regression analyses for age and the duration of
      sexual abstinence, each successive calendar year of birth accounted for 2.6
      percent of the yearly decline in the sperm concentration and for 0.3 percent and
      0.7 percent, respectively, of the yearly declines in the percentages of motile
      and normal spermatozoa (all P < 0.001). CONCLUSIONS: During the past 20 years,
      there has been a decline in the concentration and motility of sperm and in the
      percentage of morphologically normal spermatozoa in fertile men that is
      independent of the age of the men.

PMID- 7816063
TI  - Association between plasma homocysteine concentrations and extracranial carotid
      artery stenosis.
AB  - BACKGROUND: Epidemiologic studies have identified hyperhomocysteinemia as a
      possible risk factor for atherosclerosis. We determined the risk of carotid
      artery atherosclerosis in relation to both plasma homocysteine concentrations and
      nutritional determinants of hyperhomocysteinemia. METHODS: We performed a cross
      sectional study of 1041 elderly subjects (418 men and 623 women; age range, 67 to
      96 years) from the Framingham Heart Study. We examined the relation between the
      maximal degree of stenosis of the extracranial carotid arteries (as assessed by
      ultrasonography) and plasma homocysteine concentrations, as well as plasma
      concentrations and intakes of vitamins involved in homocysteine metabolism,
      including folate, vitamin B12, and vitamin B6. The subjects were classified into
      two categories according to the findings in the more diseased of the two carotid
      vessels: stenosis of 0 to 24 percent and stenosis of 25 to 100 percent. RESULTS:
      The prevalence of carotid stenosis of > or = 25 percent was 43 percent in the men
      and 34 percent in the women. The odds ratio for stenosis of > or = 25 percent was
      2.0 (95 percent confidence interval, 1.4 to 2.9) for subjects with the highest
      plasma homocysteine concentrations (> or = 14.4 mumol per liter) as compared with
      those with the lowest concentrations (< or = 9.1 mumol per liter), after
      adjustment for sex, age, plasma high-density lipoprotein cholesterol
      concentration, systolic blood pressure, and smoking status (P < 0.001 for trend).
      Plasma concentrations of folate and pyridoxal-5'-phosphate (the coenzyme form of
      vitamin B6) and the level of folate intake were inversely associated with carotid
      artery stenosis after adjustment for age, sex, and other risk factors.
      CONCLUSIONS: High plasma homocysteine concentrations and low concentrations of
      folate and vitamin B6, through their role in homocysteine metabolism, are
      associated with an increased risk of extracranial carotid-artery stenosis in the
      elderly.

PMID- 7816061
TI  - Oxygen free radicals and calcium homeostasis in the heart.
AB  - Many experiments have been done to clarify the effects of oxygen free radicals on
      Ca2+ homeostasis in the hearts. A burst of oxygen free radicals occurs
      immediately after reperfusion, but we have to be reminded that the exact levels
      of oxygen free radicals in the hearts are yet unknown in both physiological and
      pathophysiological conditions. Therefore, we should give careful consideration to
      this point when we perform the experiments and analayze the results. It is,
      however, evident that Ca2+ overload occurs when the hearts are exposed to an
      excess amount of oxygen free radicals. Though ATP-independent Ca2+ binding is
      increased, Ca2+ influx through Ca2+ channel does not increase in the presence of
      oxygen free radicals. Another possible pathway through which Ca2+ can enter the
      myocytes is Na(+)-Ca2+ exchanger. Although, the activities of Na(+)-K+ ATPase and
      Na(+)-Ca2+ exchanger. Although, the activities of Na(+)-H+ exchange are inhibited
      by oxygen free radicals, it is not known whether intracellular Na+ level
      increases under oxidative stress or not. The question has to be solved for the
      understanding of the importance of Na(+)-Ca2+ exchange in Ca2+ influx process
      from extracellular space. Another question is 'which way does Na(+)-Ca2+ exchange
      work under oxidative stress? Net influx or efflux of Ca2+?' Membrane permeability
      for Ca2+ may be maintained in a relatively early phase of free radical injury.
      Since sarcolemmal Ca(2+)-pump ATPase activity is depressed by oxygen free
      radicals, Ca2+ extrusion from cytosol to extracellular space is considered to be
      reduced. It has also been shown that oxygen free radicals promote Ca2+ release
      from sarcoplasmic reticulum and inhibit Ca2+ sequestration to sarcoplasmic
      reticulum. Thus, these changes in Ca2+ handling systems could cause the Ca2+
      overload due to oxygen free radicals.

PMID- 7816064
TI  - Methotrexate for the treatment of Crohn's disease. The North American Crohn's
      Study Group Investigators.
AB  - BACKGROUND: Although corticosteroids are highly effective in improving symptoms
      of Crohn's disease, they may have substantial toxicity. In some patients,
      attempts to discontinue corticosteroids are unsuccessful. METHODS: We conducted a
      double-blind, placebo-controlled multicenter study of weekly injections of
      methotrexate in patients who had chronically active Crohn's disease despite a
      minimum of three months of prednisone therapy. Patients were randomly assigned to
      treatment with intramuscular methotrexate (25 mg once weekly) or placebo for 16
      weeks. The patients also received prednisone (20 mg once a day), which was
      tapered over 10 weeks unless their condition worsened. The primary outcome
      measure was clinical remission at the end of the 16-week trial. Remission was
      defined by the discontinuation of prednisone and a score of < or = 150 points on
      the Crohn's Disease Activity Index. RESULTS: A total of 141 patients were
      randomly assigned in a 2:1 ratio to methotrexate (94 patients) or placebo (47
      patients). After 16 weeks, 37 patients (39.4 percent) were in clinical remission
      in the methotrexate group, as compared with 9 patients (19.1 percent) in the
      placebo group (P = 0.025; relative risk, 1.95; 95 percent confidence interval,
      1.09 to 3.48). The patients in the methotrexate group received less prednisone
      overall than those in the placebo group (P = 0.026). The mean (+/- SE) score on
      the Crohn's Disease Activity Index after 16 weeks of treatment was significantly
      lower in the methotrexate group (162 +/- 12) than in the placebo group (204 +/-
      17, P = 0.002). The changes in quality-of-life scores and serum orosomucoid
      concentrations were similar. In the methotrexate group, 16 patients (17 percent)
      withdrew from treatment because of adverse events (including asymptomatic
      elevation of serum aminotransferase in 7 and nausea in 6), as compared with 1
      patient (2 percent) in the placebo group. CONCLUSIONS: In a group of patients
      with chronically active Crohn's disease, methotrexate was more effective than
      placebo in improving symptoms and reducing requirements for prednisone.

PMID- 7816065
TI  - Infection with a babesia-like organism in northern California.
AB  - BACKGROUND: Human babesiosis is a tick-transmitted zoonosis associated with two
      protozoa of the family Piroplasmorida: Babesia microti (in the United States) and
      B. divergens (in Europe). Recently, infection with an unusual babesia-like
      piroplasm (designated WA1) was described in a patient from Washington State. We
      studied four patients in California who were identified as being infected with a
      similar protozoal parasite. All four patients had undergone splenectomy, three
      because of trauma and one because of Hodgkin's disease. Two of the patients had
      complicated courses, and one died. METHODS: Piroplasm-specific nuclear small
      subunit ribosomal DNA was recovered from the blood of the four patients by
      amplification with the polymerase chain reaction. The genetic sequences were
      compared with those of other known piroplasm species. Indirect immunofluorescent
      antibody testing of serum from the four patients and from other potentially
      exposed persons was performed with WA1 and babesia antigens. RESULTS: Genetic
      sequence analysis showed that the organisms from all four patients were nearly
      identical. Phylogenic analysis showed that this strain is more closely related to
      a known canine pathogen (B. gibsoni) and to theileria species than to some
      members of the genus babesia. Serum from three of the patients was reactive to
      WA1 but not to B. microti antigen. Serologic testing showed WA1-antibody
      seroprevalence rates of 16 percent (8 of 51 persons at risk) and 3.5 percent (4
      of 115) in two geographically distinct areas of northern California. CONCLUSIONS:
      A newly identified babesia-like organism causes infections in humans in the
      western United States. The clinical spectrum associated with infection with this
      protozoan ranges from asymptomatic infection or influenza-like illness to
      fulminant, fatal disease.

PMID- 7816066
TI  - Images in clinical medicine. Acupuncture-needle fragments.

PMID- 7816067
TI  - Bone marrow, cytokines, and bone remodeling. Emerging insights into the
      pathophysiology of osteoporosis.
AB  - Both osteoblasts and osteoclasts are derived from progenitors that reside in the
      bone marrow; osteoblasts belong to the mesenchymal lineage of the marrow stroma,
      and osteoclasts to the hematopoietic lineage. The development of osteoclasts from
      their progenitors is dependent on stromal-osteoblastic cells, which are a major
      source of cytokines that are critical in osteoclastogenesis, such as interleukin
      6 and interleukin-11. The production of interleukin-6 by stromal osteoblastic
      cells, as well as the responsiveness of bone marrow cells to cytokines such as
      interleukin-6 and interleukin-11, is regulated by sex steroids. When gonadal
      function is lost, the formation of osteoclasts as well as osteoblasts increases
      in the marrow, both changes apparently mediated by an increase in the production
      of interleukin-6 and perhaps by an increase in the responsiveness of bone marrow
      progenitor cells not only to interleukin-6 but also to other cytokines with
      osteoclastogenic and osteoblastogenic properties. The cellular activity of the
      bone marrow is also altered by the process of aging. Specifically, senescence may
      decrease the ability of the marrow to form osteoblast precursors. The association
      between the dysregulation of osteoclast or osteoblast development in the marrow
      and the disruption of the balance between bone resorption and bone formation,
      resulting in the loss of bone, leads to the following notion. Like homeostasis of
      other regenerating tissues, homeostasis of bone depends on the orderly
      replenishment of its cellular constituents. Excessive osteoclastogenesis and
      inadequate osteoblastogenesis are responsible for the mismatch between the
      formation and resorption of bone in postmenopausal and age-related osteopenia.
      The recognition that changes in the numbers of bone cells, rather than changes in
      the activity of individual cells, form the pathogenetic basis of osteoporosis is
      a major advance in understanding the mechanism of this disease.

PMID- 7816068
TI  - Treatment of male infertility.

PMID- 7816069
TI  - Human DNA polymorphism.

PMID- 7816070
TI  - Are semen quality and male fertility changing?

PMID- 7816071
TI  - Methotrexate for chronic diseases in adults.

PMID- 7816072
TI  - Clinical problem-solving: still hazy after all these years.

PMID- 7816073
TI  - Clinical problem-solving: still hazy after all these years.

PMID- 7816074
TI  - Clinical problem-solving: still hazy after all these years.

PMID- 7816075
TI  - Clinical problem-solving: still hazy after all these years.

PMID- 7816076
TI  - Post-remission chemotherapy for acute myeloid leukemia.

PMID- 7816077
TI  - Post-remission chemotherapy for acute myeloid leukemia.

PMID- 7816078
TI  - Roth's spots in leukemic retinopathy.

PMID- 7816079
TI  - More on primary biliary cirrhosis in monozygotic twins.

PMID- 7816080
TI  - Drug malabsorption and resistant tuberculosis in HIV-infected patients.

PMID- 7816081
TI  - More on hantavirus in New England and New York.

PMID- 7816082
TI  - More on hantavirus in New England and New York.

PMID- 7816083
TI  - The cat and the catheter.

PMID- 7816084
TI  - The terrier and the tendinitis.

PMID- 7816085
TI  - AIDS. Virological mayhem.

PMID- 7816086
TI  - Impact craters. Under the ringed basins.

PMID- 7816087
TI  - Molecular recognition. Crystallographic antibodies.

PMID- 7816088
TI  - Neurobiology. Thorny issues in neurons.

PMID- 7816089
TI  - Exercise and brain neurotrophins.

PMID- 7816090
TI  - Dorsoventral axis inversion.

PMID- 7816091
TI  - Dorsoventral axis in version.

PMID- 7816092
TI  - Bet on positional information.

PMID- 7816093
TI  - Cation selectivity in ion channels.

PMID- 7816094
TI  - Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection.
AB  - Treatment of infected patients with ABT-538, an inhibitor of the protease of
      human immunodeficiency virus type 1 (HIV-1), causes plasma HIV-1 levels to
      decrease exponentially (mean half-life, 2.1 +/- 0.4 days) and CD4 lymphocyte
      counts to rise substantially. Minimum estimates of HIV-1 production and clearance
      and of CD4 lymphocyte turnover indicate that replication of HIV-1 in vivo is
      continuous and highly productive, driving the rapid turnover of CD4 lymphocytes.

PMID- 7816095
TI  - Friction melt distribution in a multi-ring impact basin.
AB  - It is generally accepted that multi-ring basins are the consequence of very large
      impacts, but the mechanism by which they form is still a matter of contention.
      Most of what is currently known about multi-ring basins is based on remote
      studies of the Moon and, to a lesser extent, Mars and Mercury. But at least two
      multi-ring impact basins have been recognized on Earth--the Sudbury (Canada) and
      Vredefort (South Africa) impact structures--providing an opportunity to study
      their properties directly. Here we describe the distribution of friction melt
      (pseudotachylyte) in the floor of the Sudbury impact basin. Although the veins
      and dykes of pseudotachylyte decrease in both thickness and frequency of
      occurrence towards the basin periphery, the greatest volumes of friction melt
      appear to define four rings around the central impact melt sheet. Field evidence
      indicates that the rings originated as zones of large displacement, which
      facilitated localized frictional melting of the basin floor during the
      modification (collapse) stage of the cratering process. By analogy, we argue that
      the rings of other multi-ring impact basins are also likely to be the remnants of
      such large-displacement fault zones.

PMID- 7816096
TI  - Reduced hippocampal LTP and spatial learning in mice lacking NMDA receptor
      epsilon 1 subunit.
AB  - The NMDA (N-methyl-D-aspartate) receptor channel is important for synaptic
      plasticity, which is thought to underlie learning, memory and development. The
      NMDA receptor channel is formed by at least two members of the glutamate receptor
      (GluR) channel subunit families, the GluR epsilon (NR2) and GluR zeta (NR1)
      subunit families. The four epsilon subunits are distinct in distribution,
      properties and regulation. On the basis of the Mg2+ sensitivity and expression
      patterns, we have proposed that the epsilon 1 (NR2A) and epsilon 2 (NR2B)
      subunits play a role in synaptic plasticity. Here we show that targeted
      disruption of the mouse epsilon 1 subunit gene resulted in significant reduction
      of the NMDA receptor channel current and long-term potentiation at the
      hippocampal CA1 synapses. The mutant mice also showed a moderate deficiency in
      spatial learning. These results support the notion that the NMDA receptor channel
      dependent synaptic plasticity is the cellular basis of certain forms of learning.

PMID- 7816097
TI  - Subthreshold synaptic Ca2+ signalling in fine dendrites and spines of cerebellar
      Purkinje neurons.
AB  - The conventional view of synaptic integration is that it results from the simple
      summation of electrical signals produced by each active synapse innervating a
      given neuron. However, because synaptic action can go beyond the production of
      postsynaptic electrical signals, to include intracellular biochemical events such
      as the generation of second messengers, it is possible that synaptic integration
      could occur at another level. We have considered this possibility by examining
      changes in the dendritic concentration of the second messenger, calcium,
      resulting from subthreshold excitatory synaptic activity in cerebellar Purkinje
      neurons. We report here clear evidence that such non-electrical synaptic
      integration occurs and that it takes place in restricted dendritic compartments
      consisting of spines and adjacent fine dendrites.

PMID- 7816099
TI  - Minus-end-directed motion of kinesin-coated microspheres driven by microtubule
      depolymerization.
AB  - Dynamic changes in microtubule (MT) length have long been thought to contribute
      to intracellular motility. Both the polymerization and depolymerization of
      tubulin have been shown to do work in vitro, but the biochemical complexity of
      objects moved, such as chromosomes, has complicated the identification of
      proteins that couple MT dynamics with motility. Work with MTs grown from and
      tethered to pellicles of lysed Tetrahymena has shown that disassembly-dependent
      movement of chromosomes in vitro can be inhibited with antibodies against the
      motor domain of kinesin. To study proteins that can function in disassembly
      dependent motion, we have refined this motility assay, replacing chromosomes with
      protein-coated latex microspheres. We report here the ability of several enzymes,
      including kinesin, to support in vitro motility of latex microspheres on
      disassembling MTs (Fig. 1a). The polarity of kinesin's motor activity can be
      reversed by MT disassembly and interactions between a motor and a MT end can
      either slow or speed the rate of tubulin depolymerization.

PMID- 7816098
TI  - Neuregulins are concentrated at nerve-muscle synapses and activate ACh-receptor
      gene expression.
AB  - Two different signalling pathways mediate the localization of acetylcholine
      receptors (AChRs) to synaptic sites in skeletal muscle. The signal for one
      pathway is agrin, a protein that triggers a redistribution of previously
      unlocalized cell surface AChRs to synaptic sites. The signal for the other
      pathway is not known, but this signal stimulates transcription of AChR genes in
      myofibre nuclei near the synaptic site. Neuregulins, identified originally as a
      potential ligand for erbB2 (Neu differentiation factor, NDF), stimulate
      proliferation of Schwann cells (glial growth factor, GGF), increase the rate of
      AChR synthesis in cultured muscle cells (AChR-inducing activity) and are
      expressed in motor neurons. These results raise the possibility that neuregulin
      is the signal that activates AChR genes in synaptic nuclei. Here we show that
      neuregulin activates AChR gene expression in C2 muscle cells and that the
      neuregulin response element in the AChR delta-subunit gene is contained in the
      same 181 base pairs that confer synapse-specific expression in transgenic mice.
      We use antibodies to show that neuregulins are concentrated at synaptic sites and
      that, like the extracellular signal that stimulates synapse-specific expression,
      neuregulins remain at synaptic sites in the absence of nerve and muscle. We show
      that C2 muscle cells contain erbB2 and erbB3 messenger RNA but little or no erbB4
      mRNA, and that neuregulin stimulates tyrosine phosphorylation of erbB2 and erbB3,
      indicating that neuregulin signalling in skeletal muscle may be mediated by a
      complex of erbB2 and erbB3.

PMID- 7816100
TI  - Structural polymorphism of bacterial adhesion pili.
AB  - Bacterial adhesion pili are designed to bind specifically and maintain attachment
      of bacteria to target cells. Uropathogenic P-pili are sufficiently mechanically
      resilient to resist the cleansing action of urine flow that removes most other
      bacteria. P-pili are 68 A in diameter and approximately 1 micron long, and are
      composed of approximately 1,000 copies of the principal structural protein, PapA.
      They are attached to the outer membrane by a minor structural protein, PapH and
      are terminated by an approximately 20 A diameter fibrillus composed of PapK, PapE
      and PapF, which presents the host-binding adhesin PapG. The amino-acid sequences
      of PapA, PapE, and PapF are similar, with highly conserved C-termini being
      responsible for binding to PapD, the periplasmic chaperone. Our three-dimensional
      reconstruction indicates that pili are formed by the tight winding of a much
      thinner structure. A structural transition allows the pilus to unravel without
      depolymerizing, producing a thin, extended structure five times the length of the
      original pilus.

PMID- 7816101
TI  - The crystal structure of bluetongue virus VP7.
AB  - Bluetongue virus (BTV), a representative of the orbivirus genus of the
      Reoviridae, is considerably larger (at 80 nm across), and structurally more
      complex, than any virus for which we have comprehensive structural information.
      Orbiviruses infect mammalian hosts through insect vectors and cause economically
      important diseases of domesticated animals. They possess a segmented double
      stranded RNA genome within a capsid composed of four major types of polypeptide
      chains. An outer layer of VP2 and VP5 is removed as the virus enters the target
      cell, to leave an intact core within the cell. This core is 70 nm across and
      composed of 780 copies of VP7 (M(r) 38K) that, as trimers, form 260 'bristly'
      capsomeres clothing an inner scaffold constructed from VP3 (M(r) 103K). We report
      here the crystal structure of VP7 from BTV serotype 10, which reveals a molecular
      architecture not seen previously in viral structural proteins. Each subunit
      consists of two domains, one a beta-sandwich, the other a bundle of alpha
      helices, and a short carboxy-terminal arm which might tie trimers together during
      capsid formation. A concentration of methionine residues at the core of the
      molecule could provide plasticity, relieving structural mismatches during
      assembly.

PMID- 7816102
TI  - Darwin lives on...

PMID- 7816103
TI  - Ballot urged on ageing centre plans.

PMID- 7816104
TI  - Blood transfusion system comes under fire in Canada.

PMID- 7816105
TI  - Call for more coordination of Gulf War syndrome research.

PMID- 7816106
TI  - UK researchers highlight lack of funds for overheads.

PMID- 7816107
TI  - Roche pledges independence to new institute.

PMID- 7816108
TI  - Patent changes in India clear path for US accord.

PMID- 7816110
TI  - Ethics board members quit over 'imbalance'.

PMID- 7816109
TI  - 'Out-dated figures misled critics of space station'.

PMID- 7816111
TI  - More on DNA typing dispute.

PMID- 7816112
TI  - More on DNA typing dispute.

PMID- 7816113
TI  - More on DNA typing dispute.

PMID- 7816114
TI  - Animal welfare and the veal trade.

PMID- 7816115
TI  - Naming people lightly.

PMID- 7816116
TI  - Clinical trials face lack of minority group volunteers.

PMID- 7816117
TI  - Falling stock prices put the squeeze on biotech start-ups.

PMID- 7816118
TI  - Neuroscientist tipped as new Science editor.

PMID- 7816119
TI  - DNA repair, sry gene share Jeantet prizes.

PMID- 7816120
TI  - Wrong move.

PMID- 7816121
TI  - Patenting of human genes.

PMID- 7816122
TI  - Duesberg and the new view of HIV.

PMID- 7816123
TI  - Evolutionary biology. All's fair when love is war.

PMID- 7816124
TI  - Synthetic chemistry. Combating cholesterol.

PMID- 7816125
TI  - Manufacture of a marine menace.

PMID- 7816126
TI  - Signal transduction. Phospholipids in action.

PMID- 7816127
TI  - Visual perception. Vision without awareness.

PMID- 7816128
TI  - Protein engineering. Hunting haemoglobin.

PMID- 7816129
TI  - Catalytic antibodies. How to promote proton transfer.

PMID- 7816130
TI  - Cell adhesion. Cryptic sites in vinculin.

PMID- 7816131
TI  - Neuropsychology. Modulation by instruction.

PMID- 7816132
TI  - Transcription. Zen and the art of Fos and Jun.

PMID- 7816133
TI  - Matching needed for stereopsis.

PMID- 7816134
TI  - Punishment in animal societies.
AB  - Although positive reciprocity (reciprocal altruism) has been a focus of interest
      in evolutionary biology, negative reciprocity (retaliatory infliction of fitness
      reduction) has been largely ignored. In social animals, retaliatory aggression is
      common, individuals often punish other group members that infringe their
      interests, and punishment can cause subordinates to desist from behaviour likely
      to reduce the fitness of dominant animals. Punishing strategies are used to
      establish and maintain dominance relationships, to discourage parasites and
      cheats, to discipline offspring or prospective sexual partners and to maintain
      cooperative behaviour.

PMID- 7816135
TI  - Regulation of PLC-mediated signalling in vivo by CDP-diacylglycerol synthase.
AB  - CDP-diacylglycerol synthase (CDS) is an enzyme required for the regeneration of
      the signalling molecule phosphatidylinositol-4,5-bisphosphate (PtdlnsP2) from
      phosphatidic acid. A photo-receptor cell-specific isoform of CDS from Drosophila
      is a key regulator of phototransduction, a G-protein-coupled signalling cascade
      mediated by phospholipase C. cds mutants cannot sustain a light-activated current
      as a result of depletion of PtdlnsP2. Overexpression of CDS increases the
      amplitude of the light response, demonstrating that availability of PtdlnsP2 is a
      determinant in the gain of this pathway. cds mutants undergo light-dependent
      retinal degeneration which can be suppressed by a mutation in phospholipase C.
      Thus, enzymes involved in PtdlnsP2 metabolism regulate phosphoinositide-mediated
      signalling cascades in vivo.

PMID- 7816136
TI  - Large rate accelerations in antibody catalysis by strategic use of haptenic
      charge.
AB  - General acid-base catalysis contributes substantially to the efficacy of many
      enzymes, enabling an impressive array of eliminations, isomerizations,
      racemizations, hydrolyses and carbon-carbon bond-forming reactions to be carried
      out with high rates and selectivities. The fundamental challenge of exploiting
      similar effects in designed catalysts such as catalytic antibodies is that of
      correctly positioning the catalytic groups in an appropriate active-site
      microenvironment. Charge complementarity between antibody and hapten (the
      template used to induce an antibody) has been used successfully in a number of
      instances to elicit acids and bases within immunoglobulin combining sites, but
      the activities of the catalysts obtained by this strategy are generally
      considerably lower than those of natural enzymes. Here we report that by
      optimizing hapten design and efficiently screening the immune response,
      antibodies can be obtained that act effectively as general base catalysts. Thus a
      cationic hapten correctly mimicking the transition-state geometry of all reacting
      bonds and bearing little resemblance to the reaction product has yielded
      carboxylate-containing antibodies that catalyse an E2 elimination with more than
      10(3) turnovers per active site and rate accelerations of greater than 10(8).
      These results demonstrate that very large effects can be achieved by strategic
      use of haptenic charge.

PMID- 7816137
TI  - Cost of mating in Drosophila melanogaster females is mediated by male accessory
      gland products.
AB  - Female Drosophila melanogaster with environmentally or genetically elevated rates
      of mating die younger than controls. This cost of mating is not attributable to
      receipt of sperm. We demonstrate here that seminal fluid products from the main
      cells of the male accessory gland are responsible for the cost of mating in
      females, and that increasing exposure to these products increases female death
      rate. Main-cell products are also involved in elevating the rate of female egg
      laying, in reducing female receptivity to further matings and in removing or
      destroying sperm of previous mates. The cost of mating to females may therefore
      represent a side-effect of evolutionary conflict between males.

PMID- 7816138
TI  - Transplanting a unique allosteric effect from crocodile into human haemoglobin.
AB  - Crocodiles are able to remain under water for more than one hour without
      surfacing to breathe and often kill their prey by drowning it. How do crocodiles
      stay under water for a long time? When they hold their breath, bicarbonate ions,
      the final product of respiration, accumulate and drastically reduce the oxygen
      affinity of haemoglobin, releasing a large fraction of haemoglobin-bound oxygen
      into the tissues. We have now located the bicarbonate-ion-binding site at the
      alpha 1 beta 2-subunit interface by making various human-crocodile chimaeric
      haemoglobins. Furthermore, we have been able to transplant the bicarbonate effect
      into human haemoglobin by replacing only a few residues, even though the amino
      acid sequence identity between crocodile (Crocodylus niloticus) and human
      haemoglobins is only 68% for the alpha- and 51% for the beta-subunit. These
      results indicate that an entirely new function which enables species to adapt to
      a new environment could evolve in a protein by a relatively small number of amino
      acid substitutions in key positions.

PMID- 7816139
TI  - Blindsight in monkeys.
AB  - Blindsight, the visually evoked voluntary responses of patients with striate
      cortical destruction that are demonstrated despite a phenomenal blindness, has
      attracted attention from neuroscientists and philosophers interested in problems
      of perceptual consciousness and its neuronal basis. It is assumed to be mediated
      by the numerous extra-geniculostriate cortical retinofugal pathways whose
      properties are studied primarily in monkeys. Like patients with blindsight,
      monkeys with lesions of the primary visual cortex can learn to detect, localize
      and distinguish between visual stimuli presented within their visual field
      defects. Although the patients deny seeing the stimuli they can nevertheless
      respond to (by forced-choice guessing) in their phenomenally blind fields, it is
      not known whether the monkeys experience the same absence of phenomenal vision.
      To determine whether they too have blindsight, or whether they actually see the
      stimuli in their field defects, monkeys who showed excellent detection in tasks
      where a visual stimulus was presented on every trial, albeit at different
      positions, were tested in a signal-detection task in which half the trials were
      blank trials, with no visual stimulus. They classified the visual stimuli
      presented in the field defect as blank trials, demonstrating, like patients,
      blindsight rather than degraded real vision.

PMID- 7816140
TI  - Blood flow changes in human somatosensory cortex during anticipated stimulation.
AB  - Positron emission tomography (PET) measurements of brain blood flow were used to
      monitor changes in the human primary and secondary somatosensory cortices during
      the period when somatosensory stimuli were expected. In anticipation of either
      focal or innocuous touching, or localized, painful shocks, blood flow decreased
      in parts of the primary somatosensory cortex map located outside the
      representation of the skin area that was the target of the expected stimulus.
      Specifically, attending to an impending stimulus to the fingers produced a
      significant decrease in blood flow in the somatosensory zones for the face,
      whereas attending to stimulation of the toe produced decreases in the zones for
      the fingers and face. Decreases were more prominent in the side ipsilateral to
      the location of the expected stimulus. No significant changes in blood flow
      occurred in the region of the cortex representing the skin locus of the awaited
      stimulation. These results are concurrent with a model of spatial attention in
      which potential signal enhancement may rely on generalized suppression of
      background activity.

PMID- 7816141
TI  - The site and stage of anti-DNA B-cell deletion.
AB  - Antibodies to DNA and nucleoproteins are found in sera of individuals with
      systemic autoimmune disease. In the population (and in the autoimmune mouse
      strain MRL/lpr) there is a great variety of such antinuclear antibodies, but
      individuals with systemic lupus erythematosus or single MRL mice express a subset
      only of the antinuclear specificities found in the population. These observations
      have been interpreted to mean that these antibodies arise by immunization. The
      oligoclonal nature of the autoantibody response and the evidence of selection
      acting on somatically mutated autoantibodies favour this interpretation. Specific
      activation of autoantibodies in disease implies either that autoantibodies are
      regulated in non-diseased individuals or that autoantigen availability is
      variable. The former has been demonstrated in anti-DNA transgenic mice. In normal
      mice, transgene-encoded antibodies against double-stranded (ds) DNA are not
      expressed in serum or on B cells. Here we describe modified anti-dsDNA transgenic
      mice which allow us to study the site and developmental stage at which such B
      cell regulation occurs. This model shows that in normal mice B cells expressing
      anti-DNA specificity are deleted in the bone marrow at a pre-B to immature B
      transitional stage.

PMID- 7816142
TI  - Differential production of interferon-gamma and interleukin-4 in response to Th1-
      and Th2-stimulating pathogens by gamma delta T cells in vivo.
AB  - Exposure to various pathogens can stimulate at least two patterns of cytokine
      production by CD4-positive T cells. Responses that result in secretion of
      interferon-gamma (IFN-gamma), lymphotoxin and interleukin-2 (IL-2) are classified
      as T-helper-1 (Th1); CD4+ T-cell production of IL-4, IL-5, IL-9, IL-10 and IL-13
      is called a T-helper-2 response (Th2). Differentiation of CD4+ T cells into
      either Th1 or Th2 cells is influenced by the cytokine milieu in which the initial
      antigen priming occurs. Here we use flow cytometry to identify the presence of
      intracellular cytokines (cytoflow) and analyse T-cell production of IFN-gamma and
      IL-4 from mice infected with Listeria monocytogenes or Nippostrongylus
      brasiliensis. We show that T cells bearing gamma delta receptors discriminate
      early in infection between these two pathogens by producing cytokines associated
      with the appropriate T-helper response. Our results demonstrate that gamma delta
      T cells are involved in establishing primary immune responses.

PMID- 7816143
TI  - Crystal structure of the heterodimeric bZIP transcription factor c-Fos-c-Jun
      bound to DNA.
AB  - The Fos and Jun families of eukaryotic transcription factors heterodimerize to
      form complexes capable of binding 5'-TGAGTCA-3' DNA elements. We have determined
      the X-ray crystal structure of a heterodimer of the bZIP regions of c-Fos and c
      Jun bound to DNA. Both subunits form continuous alpha-helices. The carboxy
      terminal regions form an asymmetric coiled-coil, and the amino-terminal regions
      make base-specific contacts with DNA in the major groove. Comparison of the two
      crystallographically distinct protein-DNA complexes show that the coiled-coil is
      flexibly joined to the basic regions and that the Fos-Jun heterodimer does not
      recognize the asymmetric 5'-TGAGTCA-3' recognition element in a unique
      orientation. There is an extensive network of electrostatic interactions between
      subunits within the coiled-coil, consistent with proposals that these
      interactions determine preferential formation of the heterodimer over either of
      the homodimers.

PMID- 7816144
TI  - F-actin binding site masked by the intramolecular association of vinculin head
      and tail domains.
AB  - Although vinculin is present at all sites of F-actin attachment to plasma
      membranes and is required for linkage of myofibrils to sarcolemma, it is unclear
      how it promotes attachment of actin to membranes. Because biochemical evidence
      for a direct interaction of vinculin with F-actin is controversial, current
      models of actin-membrane linkages depict only an indirect role for vinculin, as a
      tether for alpha-actinin. We demonstrate here that an intramolecular association
      between the 95K head and 30K tail domains of vinculin masks an F-actin binding
      site present in the carboxy-terminal tail domain. Cosedimentation and
      crosslinking assays, and direct visualization by transmission electron
      microscopy, reveal an interaction between F-actin and a bacterially expressed
      fusion protein containing amino acids 811-1066 of vinculin, and between F-actin
      and a proteolytic fragment of vinculin containing amino acids 858-1066. Vinculin
      itself neither cosediments with nor crosslinks F-actin. The amino-terminal 95K
      head fragment of vinculin, but not intact vinculin, inhibits both cosedimentation
      and crosslinking. We propose that assembly of vinculin into an adherens junction
      involves disruption of the head-tail interaction, revealing a site that mediates
      microfilament attachment.

PMID- 7816146
TI  - The University of Nebraska's College of Medicine primary care community education
      networks.

PMID- 7816145
TI  - Penicillin acylase has a single-amino-acid catalytic centre.
AB  - Penicillin acylase (penicillin amidohydrolase, EC 3.5.1.11) is widely distributed
      among microorganisms, including bacteria, yeast and filamentous fungi. It is used
      on an industrial scale for the production of 6-aminopenicillanic acid, the
      starting material for the synthesis of semi-synthetic penicillins. Its in vivo
      role remains unclear, however, and the observation that expression of the
      Escherichia coli enzyme in vivo is regulated by both temperature and phenylacetic
      acid has prompted speculation that the enzyme could be involved in the
      assimilation of aromatic compounds as carbon sources in the organism's free
      living mode. The mature E. coli enzyme is a periplasmic 80K heterodimer of A and
      B chains (209 and 566 amino acids, respectively) synthesized as a single
      cytoplasmic precursor containing a 26-amino-acid signal sequence to direct export
      to the cytoplasm and a 54-amino-acid spacer between the A and B chains which may
      influence the final folding of the chains. The N-terminal serine of the B chain
      reacts with phenylmethylsulphonyl fluoride, which is consistent with a catalytic
      role for the serine hydroxyl group. Modifying this serine to a cysteine
      inactivates the enzyme, whereas threonine, arginine or glycine substitution
      prevents in vivo processing of the enzyme, indicating that this must be an
      important recognition site for cleavage. Here we report the crystal structure of
      penicillin acylase at 1.9 A resolution. Our analysis shows that the environment
      of the catalytically active N-terminal serine of the B chain contains no adjacent
      histidine equivalent to that found in the serine proteases. The nearest base to
      the hydroxyl of this serine is its own alpha-amino group, which may act by a new
      mechanism to endow the enzyme with its catalytic properties.

PMID- 7816147
TI  - The Nebraska Hospital-Medical Liability Act: a successful approach to medical
      malpractice caps.

PMID- 7816148
TI  - Treatment of chronic tibial osteomyelitis, segmental bone loss, and soft tissue
      defect by bone transplant.
AB  - New methods of treatment have greatly improved the success of limb salvage in
      severe lower extremity trauma. We report the use of a microvascular free tissue
      transfer and distraction osteogenesis in the reconstruction of soft tissue and
      bone defects complicated by infection. Soft tissue coverage and bony
      stabilization by external fixation resulted in eradication of the infection. The
      external fixator also allowed bone transport and regeneration to overcome a bone
      defect of approximately 6 cm. Bone transportation can be accomplished in a distal
      to proximal direction if the situation necessitates it. These techniques are
      extremely versatile and useful in the treatment of bone and soft tissue defect.

PMID- 7816149
TI  - [Genetic association in psychiatric diseases. Concepts and findings].

PMID- 7816150
TI  - [Current status of biochemical hypotheses in the pathogenesis of schizophrenia].
AB  - The search for neurochemical correlates of schizophrenic psychopathology is a
      major issue of modern multidimensional approaches to the schizophrenic psychoses.
      The main focus of interest has shifted in recent years from the classical
      dopamine hypothesis to an increasing set of various neurotransmitter imbalance
      models of schizophrenic psychoses involving not only the dopaminergic system but
      also glutamatergic, serotonergic, cholinergic, GABAergic or peptidergic neuron
      systems. The pharmacology and phenomenology of phencyclidine-induced model
      psychoses and a substantial body of neurochemical evidence in human schizophrenic
      brain suggest that reduced glutamatergic transmission is a key feature in the
      pathobiochemistry of schizophrenic psychoses and might trigger episodic dopamine
      excess states, the putative correlates of psychotic relapse. Given the multiple
      types of natural course, of severity and of prognosis, it is almost inescapable
      to conclude that there will be no unitary biochemical abnormality underlying the
      schizophrenic psychoses. None of the available biochemical models of
      schizophrenia pathogenesis is corroborated by sufficient experimental data. The
      biochemical data gathered so far have not had a major impact on diagnostic or
      therapeutic considerations in the schizophrenic psychoses.

PMID- 7816151
TI  - [Pharmacotherapy of borderline disorders. A review of the literature].
AB  - In principle therapy of borderline personality disorder is a psychotherapeutic
      one. But often situations occur, which make a pharmacological treatment
      inevitable. The overall contradictory literature is reviewed and a critical
      overview is given about the psychopharmaca--substance-groups and substances--and
      their effects in treatment. Finally general recommendations for medication are
      given.

PMID- 7816152
TI  - [Standardized diagnosis of social adjustment. Assessment instruments for
      ambulatory and inpatient psychiatric care].
AB  - The diagnosis of social adjustment has been shown to be a fundamental tool for
      the planning of successful rehabilitation in patients with mental disorders
      treated in an out- and inpatient setting, for documentation of the course of the
      illness and the assessment of outcome. In the last few years, a number of
      different instruments have been devised. This paper presents the most current
      instruments: global assessment instruments, structured and semistructured
      interview questionnaires and observation instruments such as time-sampling
      checklists and rating scales. Depending on the scope of the assessment, there are
      specific instruments, some of them translated into German, to determine
      prognosis, degree of social impairment, available resources etc.

PMID- 7816153
TI  - [Modified insulin treatment of therapy refractory schizophrenic disorders].
AB  - Subliminal hypoglycemia therapy (subcoma therapy, modified insulin therapy) is
      rarely practised in modern psychiatry. This study reports on the therapy of 105
      patients (2619 single treatments) suffering from therapy-resistant schizophrenia.
      Evaluation was retrospective. Remarkably, 46.7% of the patients responded
      positively to a 4-6 week course of insulin therapy. In 26.6%, the effect was
      moderate. Tolerance ist good.

PMID- 7816154
TI  - [The apolipoprotein E-epsilon 4 allele is a risk factor for Alzheimer disease
      with early and late onset].
AB  - The apolipoprotein E genotype was determined in 50 patients with clinically
      diagnosed and prospectively confirmed Alzheimer's disease of mild to moderate
      severity and in 50 healthy age- and sex-matched controls. The frequency of the
      epsilon 4 allele was increased in the patients irrespective of the age at onset
      and of a possible familial transmission of the disease. It was associated with a
      relative risk of 2.97. In patients who experienced first symptoms after the age
      of 65 years there was an inverse correlation between the number of epsilon 4
      alleles and age at onset. The results suggest that in the absence of amyloid
      precursor protein mutations and of a gene which has not yet been precisely
      localized on chromosome 14, apolipoprotein E is involved in the pathogenesis of
      Alzheimer's disease. It probably exerts its influence by an acceleration or
      retardation of amyloid formation and/or tau hyperphosphorylation.

PMID- 7816155
TI  - [Apolipoprotein E and Alzheimer dementia. Personal results and brief literature
      review].
AB  - The apolipoprotein E allele (Apo-E gene) status was determined in 147 individuals
      from a longitudinal study. 53 satisfied NINCDS-ADRDA criteria for probable or
      possible Alzheimer's disease (AD), 37 were non-demented healthy controls. 31
      patients with AD had one or two Apo-E 4 alleles (phenotypes 1 x 4-2; 20 x 4-3; 10
      x 4-4) compared with only 9 controls (8 x 4-3; 1 x 4-4). Within the AD group,
      patients homozygous for Apo-E 4 had an earlier onset of illness (7 of 10 cases
      were presenile) and more severe cognitive impairment at the time of examination
      after similar durations of illness as patients without Apo-E 4. This may reflect
      an influence of the Apo-E 4 gene dosage on the onset and course of illness, which
      is probably independent of chromosome 14 mutations.

PMID- 7816156
TI  - [Informed consent requirement in treatment with clozapine according to section
      1904 of the patient rights law?].
AB  - Clozapine-treatment of schizophrenic psychoses under observation of the
      producer's directions regarding indication, warnings, information of the patient
      and control-examinations is no measure which entails (according to section 1904
      of German Civil Code-"Betreuungsrecht") the existing risk that the person
      concerned will die or suffer a serious or lasting health-injury. Therefore, in
      case of patient's inability to consent, the curator's approval after proper
      information is regarded to be sufficient in most cases of an intended treatment
      with clozapine. An approval by the Guardianship Court according to section 1904
      should be applied for when--because of medical reasons after evaluating risks and
      benefits--clozapine-treatment is taken into consideration despite risks and
      contraindications according to the producer's informations.

PMID- 7816157
TI  - [Generalized epileptic seizures in treatment with clozapine. Incidence, types,
      prognosis and recommendations with reference to therapeutic strategies].

PMID- 7816158
TI  - [Tardive dystonia. A rare neuroleptic-induced disease picture].
AB  - This paper reports on a case of spasmodic torticollis after longterm treatment
      with neuroleptics. This form of dystonia is called tardive dystonia to
      distinguish it from tardive dyskinesia. Its pathophysiology is unknown.
      Pathological changes are described in the basal ganglia. Increased signal was
      found on magnetic resonance imaging on both sides of the basal ganglia reflecting
      structural lesions. These structural changes, together with neuroleptic
      medication, represent predisposing factors for the manifestation of tardive
      dystonia.

PMID- 7816159
TI  - [Is there a special indication for fluphenazine in therapy refractory
      hallucinations?].
AB  - On one of our rehabilitation wards, we observed several schizophrenic patients
      with therapy resistant hallucinations to exhibit complete recovery after being
      given fluphenazine (2-7.5 mg a day, orally); previously, they were found to be
      therapy resistant on other potent neuroleptics, including clozapine. It appears
      that in selected patients fluphenazine has a special antihallucinatory effect.

PMID- 7816160
TI  - [MDMA ("Ecstasy")--a dangerous drug or psychotherapeutic drug?].
AB  - Abuse of 3,4-methylenedioxymethamphetamine (MDMA) is increasing, as is the number
      of deaths associated with "ecstasy". The history, effects and side effects of
      this controversial psychotropic substance are presented. Its relevance for
      clinical practice is shown.

PMID- 7816161
TI  - [Demography of nephrologists in France].
AB  - This study used data from a mailing sent during years 1991-1992 to 1096
      physicians. The response rate was 94%, providing a registry. The data showed the
      different kinds of diploma of the certified nephrologists. The vast majority of
      nephrologists ranges from 35 to 49 years old with a tendancy to be younger if
      they are working in a renal transplant unit. The number of retirement per year is
      given from 1993 to 2011 in order to evaluate the number of nephrologist to be
      certified in the future.

PMID- 7816162
TI  - [Etiologic aspects of acute renal insufficiency in the adult].
AB  - Acute renal failure (ARF) is a syndrome with numerous underlying causal
      conditions--upon which depends vital prognosis, and various pathogenetic
      mechanisms of either functional or lesional nature--upon which depends renal
      prognosis. Lesions can affect different parts of the renal parenchyma, and may or
      may not be reversible. Here are described: a) the basic investigations that allow
      to diagnose both the underlying conditions and the mechanisms of ARF in adults;
      b) an etiologic classification of ARF. Elements of the renal syndrome, composed
      of anamnestic, clinical, laboratory, imaging and, if necessary, histological
      data, have to be gathered in each individual case. Emphasis is laid on some forms
      of ARF of increasing frequency: ARF induced by angiotensin-converting enzyme
      inhibitors, rapidly progressive glomerulonephritides, necrotizing vasculitides
      with circulating antineutrophil cytoplasmic antibodies and hemolytic-uremic
      syndrome. Early diagnosis of spontaneously non-reversible parenchymal lesions
      leads to timely etiopathogenic therapy and increases the likelihood of renal
      anatomical and functional recovery.

PMID- 7816163
TI  - [Renal manifestation in POEMS syndrome].
AB  - The authors report four cases of POEMS Syndrome with renal involvement. Two had
      renal failure and mild proteinuria. The two others had hyporeninemic
      hypoaldosteronism with type IV renal tubular acidosis in the first and
      hyperkalemia alone in the second. In the two cases, renal biopsy showed mesangial
      proliferation. Evolution was favourable when the plasma cell proliferation could
      be checked. In POEMS pathophysiology of renal involvement remains unknown.
      Soluble factor(s) produced by plasma cells may be responsible for most signs and
      symptoms perhaps as a result of increased vascular permeability.

PMID- 7816164
TI  - [Renal transplantation in Bourneville tuberous sclerosis].
AB  - A 37 year-old patient with tuberous sclerosis and renal failure had renal
      transplantation performed, after 21 months of hemodialysis treatment and cerebral
      glioma removal, with good results 7 years later. In order to assess renal
      transplantation as a treatment for end-stage renal failure of tuberous sclerosis,
      we have reviewed the literature. 14 observations could be analysed: the patients
      were young with a mean age of 29.2 years, women in majority, with minor
      neurologic involvement. Because of the risks of neoplastic transformation and
      angiomyolipoma bleeding, bilateral nephrectomy is cautious, before or during the
      renal transplantation. Otherwise a close monitoring of the native kidneys by CT
      scan is necessary. So the patients with tuberous sclerosis are good candidates
      for renal transplantation, with the same results as other patients of the same
      age, with no aggravation of the neurologic disorders, even when a cerebral tumor
      has been removed, as in our case.

PMID- 7816165
TI  - [Parametric analysis of survival in kidney transplantation].
AB  - Biparametric Weibull's model was used to analyze survival of 615 renal cadaveric
      allografts performed at our center from January 1980 to December 1992. The model
      adequately describes patient's well as immunological and total graft survival
      during the total follow-up period extending from the first to the 100th
      postoperative month. After logarithmic transformation of the coordinates, the
      survival function may be represented as a straight regression line whose
      parameters are those of the model. Four factors significantly influence total
      graft survival according to multivariate analyses using Cox's and Weibull's
      models: donor's age and sex, HLA-B+DR donor-recipient compatibility and
      immunosuppression. Both models are equally effective to uncover those factors but
      the overall statistical significance of Weibull's model is greater than that of
      Cox's model. Functional graft half-live calculated from the time of
      transplantation may be easily estimated from the values of several predictive
      variables.

PMID- 7816166
TI  - [Possible indications for human recombinant growth hormone in adults: current
      data and future perspectives].
AB  - Growth hormone (GH) secretion persists during adulthood with mostly metabolic
      effects, stimulating lipolysis and protein synthesis. Besides GH-deficient
      patients, other adult patients might in the future benefit from recombinant GH
      (rhGH) therapy. These conditions would mainly include: 1. Highly catabolic states
      in intensive-care patients (conflicting results); 2. Osteoporosis, because of
      significant, although moderate improvement in bone density; 3. Aging:
      compensating for age-related GH-deficiency has yielded positive results
      concerning nutritional status; in the elderly however, the risk of side-effects,
      above all hypervolemia, should not be overlooked; 4. Uremia, frequently
      associated with poor nutritional status: preliminary results in hemodialysis
      patients are certainly encouraging; rhGH coupled with intradialytic parenteral
      nutrition might be particularly efficient. Treatment of uremic patients before
      end-stage renal failure seems also to be contemplated since, in spite of
      hyperfiltration and glomerulosclerosis observed in rats receiving high doses of
      rhGH, no case of worsened renal failure has ever been reported in pre-dialysis
      children treated for stunted growth.

PMID- 7816167
TI  - [Apropos of rifampicin-protamine protocol used in the prevention of infections
      from central venous catheters in hemodialysis].

PMID- 7816168
TI  - [Intravascular surgery].

PMID- 7816169
TI  - [Sealing effect of fibrin glue spray on protection of cerebrospinal fluid leakage
      through the dura mata].
AB  - Fibrin glue, a biologic adhesive, is made with highly concentrated human
      fibrinogen and clotting factors. It has become used frequently in neurosurgical
      procedures, in particular in the closure of the dura mata to prevent
      cerebrospinal fluid leakage. This report evaluates sealing effects of the fibrin
      glue on cerebrospinal fluid leakage through the dura. (1) Three manipulations for
      application of fibrin glue were used; i.e., layer, mixture and spray methods.
      These methods were compared to estimate their sealing effects on water leakage
      through a 1.2mm pore in an artificial dura. The burst pressure was significantly
      higher when the spray method was used than when the other two methods were used.
      (2) Dural incision was made and then sutured at intervals of 2mm, 3mm, 4mm, 6mm,
      and 8mm. Fibrin glue was applied by a spray method on the sutured dura. The burst
      pressure of the fibrin plate was over 80cmH2O on every interval of dural suture.
      (3) Dural defects 2mm, 4mm, 6mm, and 8mm in diameter were made, and then spray of
      fibrin glue was used to shield the defects. The fibrin clot spreading to the
      inner and outer surfaces of the pore defect was plug-shaped. The fibrin plug
      tolerated water pressure over 200cmH2O, in every size of pore. In conclusion, the
      optimal method for using fibrin glue on the surface of the dura was a spray
      method. Fibrin plate/clot made by the spray method sealed the dural tear or pore
      so well that it sustained a water pressure of over 80cmH2O, which is far higher
      than normal pressure of the intracranial cerebrospinal fluid.

PMID- 7816170
TI  - [Diaschisis in right putaminal hemorrhage: correlation with the degree of the
      extension to the internal capsule and the volume of hematoma].
AB  - Local cerebral lesions may cause depression of function in remote areas of the
      brain presumably by a transneural mechanism. This has been called "diaschisis".
      In the present study, regional brain blood flow in hypertensive right putaminal
      hemorrhage was studied in 33 patients (mean age, 55 year; 22 men, 11 women) to
      investigate the relationship between the degree in damage of the original lesions
      and "diaschisis". The hematoma was treated conservatively in 8 patients,
      aspirated stereotaxically in 9 patients, and evacuated through craniotomy in 16
      patients. The regional blood flow in bilateral motor cortices and bilateral
      cerebellar hemispheres was measured by a single photon emission CT with N
      isopropyl-p- [123 I] iodo-amphetamine intravenous injection, and was evaluated by
      the RI count on early image/the decay-corrected RI count on delayed image (E/D).
      The regional brain blood flow was measured for 29 to 35 days from the onset.
      There was a negative correlation between the degree of the extension to the
      internal capsule and the regional blood flow of the right motor cortex and the
      bilateral cerebellar hemispheres. There was also a negative correlation between
      the volume of the hematoma and the regional blood flow of the right motor cortex
      and the bilateral cerebellar hemispheres. The regional blood flow of the left
      motor cortex correlated with neither the degree of the extension to the internal
      capsule nor the volume of the hematoma. On the other hand, there was a positive
      correlation in the regional blood flow between the bilateral motor
      cortices.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7816171
TI  - [Synergistic effect of carboplatin and hyperthermia in rat and human glioma cell
      lines].
AB  - To assess the interaction of carboplatin and hyperthermia in vitro, the
      thermochemosensitivities of three glioma cell lines, C6 rat glioma cell line,
      human glioma cell lines T98G and KMG4, were examined by 3-(4,5-dimethylthiazol-2
      yl) -2,5 diphenyltetrazolium bromide (MTT) assay. The cell survival of each cell
      line decreased according to increasing CBDCA concentration and temperature. With
      a certain CBDCA concentration, the cell survival at following temperature was
      significantly decreased from that at 37 degrees: 43 degrees C and 44 degrees C
      for C6 cells (2.5 micrograms/ml); 41 degrees C, 42 degrees C, 43 degrees C and 44
      degrees C for C6 cells (128 micrograms/ml); 42 degrees C, 43 degrees C and 44
      degrees C for KMG4 cells (8 micrograms/ml) (CBDCA concentration within
      parentheses). It is generally considered that the highest tolerable temperature
      of normal brain is 42 degrees C for 60 minutes, while under 43 degrees C, there
      is a possibility that a sufficient tumoricidal effect might not be obtained. This
      study revealed enhanced cytotoxicity of CBDCA with hyperthermia at the
      temperature lower than 42 degrees C and suggests the possibility to gain
      increased tumoricidal effect without injuring normal brain by hyperthermia at the
      normal-tissue-tolerant temperature with systemic administration of relatively
      lower dose of CBDCA.

PMID- 7816172
TI  - [A distal posterior inferior cerebellar artery aneurysm in the fourth ventricle:
      a case report].
AB  - The authors reported a case of a fourth ventricle aneurysm originating from the
      choroidal branch of the posterior inferior cerebellar artery (PICA). A 65-year
      old woman became comatose following the acute onset of a severe headache and
      vomiting. She was moribund on admission, showing decerebrate posture. CT scan
      revealed a massive hematoma in the fourth ventricle up to the lateral ventricle.
      Extension of blood to the cisterna magna through the cerebellar vermis was also
      noted. Angiography demonstrated an aneurysm distally located on the right PICA
      across the midline. The aneurysm lodged in the choroid plexus which was
      exclusively fed by the right PICA was excised without difficulty through
      suboccipital craniectomy. Postoperative course was uneventful. She regained her
      full consciousness by two days after the operation, and was discharged with a
      minimal truncal ataxia. To our knowledge, this is the first report of a ruptured
      aneurysm developing in the choroid plexus of the fourth ventricle. Hemodynamic
      stress is speculated to be a causative factor of such a lesion.

PMID- 7816174
TI  - [A rare case of high cervical spinal cord dural arteriovenous fistula presenting
      with intracranial subarachnoid hemorrhage].
AB  - It is now recognized that spinal dural arteriovenous fistula causes myelopathy,
      resulting from congestive venous hypertension of the spinal cord. We have
      recently encountered a rare case of high cervical spinal cord dural arteriovenous
      fistula which caused intracranial subarachnoid hemorrhage. The patient was a 62
      year-old female, who had exhibited an abrupt onset of severe headache and loss of
      consciousness. Plain head CT scan revealed intracranial subarachnoid hemorrhage.
      No abnormal vascular lesions were found on the first cerebral angiography. The
      second angiographical examination demonstrated a spinal arteriovenous
      malformation at the high cervical region. A dural arteriovenous fistula around
      the right C2 nerve root was found by surgical intervention. The fistula was
      recognized between rt. C2 radicular artery and dural sheath of rt. C2 nerve root,
      draining to the epidural plexus and intradural local medullary vein. No
      serpentine coronal venous plexus on the dorsal aspect of the cervical cord was
      seen as it is in a usual dural type of spinal arteriovenous fistula. The bleeding
      point was an intradural varix of the medullary vein just where it penetrated the
      nerve root area. Feeder ligation of the C2 radicular artery and coating of the
      varix complex were performed. The postoperative course was uneventful. The
      patient was discharged from our institute with no neurological deficits.

PMID- 7816173
TI  - [A case of intracranial glioma which demonstrated extramedullary growth].
AB  - An unusual case of an intracranial glioma which demonstrated extramedullary
      growth is reported. The patient was a 39-year-old woman who had experienced
      headache, nausea and vomiting for about 1 month. On admission she showed slight
      disturbance of consciousness and bilateral papilloedema. CT scan and MR imaging
      disclosed a mass approximately 5 cm in diameter in the right frontal region, with
      clear demarcation from the neighboring gyri. Right external carotid angiogram
      revealed A-V shunts in the mass, but by right internal carotid angiogram, no
      abnormal findings were disclosed except for the deviation of normal intracranial
      vessels due to the existence of the mass. Therefore, a preoperative diagnosis of
      extramedullary tumor such as meningioma and epidermoid was made. Right frontal
      craniotomy was performed, and the tumor was proven to exist in subdural space.
      The boundary of the tumor to the brain surface was distinct except for one part.
      Histopathologically, the tumor cells had abundant eosinophillic cytoplasms, with
      eccentric-distribution of their nuclei. Furthermore, they were positive for
      staining for GFAP and S-100 protein. Therefore, a final diagnosis of gemistocytic
      astrocytoma was made. Reviewing some references the authors discuss here the form
      of development and progression of intracranial gliomas which demonstrate
      extramedullary growth such as this case.

PMID- 7816175
TI  - [Transcortical sensory aphasia in a patient with metastatic brain tumor in the
      left frontal lobe].
AB  - We reported a case of a 62-year-old right-handed woman who had transcortical
      sensory aphasia caused by a metastatic brain tumor in the left frontal lobe. She
      had mild right hemiparesis involving the face, without hyperactive tendon
      reflexes. She had neither sensory disturbance nor other cranial nerve deficits.
      Her spontaneous speech was fluent, and she sometimes had echolalia. Her object
      naming, word fluency, verbal comprehension and writing were severely disturbed.
      This contrasted with full preservation of repetition of phonemes and short
      sentences. Reading of words was preserved. CT scan revealed a subcortical lesion
      in the left superior frontal gyrus. Gd-enhanced MRI showed a ring-enhanced mass
      lesion in the frontal lobe outside of Broca's area. We thereby concluded that
      transcortical sensory aphasia may be caused by frontal lobe lesion independent of
      the perisylvian speech areas.

PMID- 7816176
TI  - [Multiple cavernous angiomas accompanied with a convexity meningioma: a case
      report].
AB  - We reported a rare case of multiple cavernous angioma accompanied with a
      convexity meningioma. A 41-year-old female developed generalized convulsion on
      October 8, 1985. Plain computed tomography (CT) scan revealed a round
      heterogeneous density mass in the right parietotemporal region, which was
      homogeneously enhanced. Angiography demonstrated a tumor stain fed by the right
      angular artery and the posterior branch of the right middle meningeal artery.
      Total removal of the tumor was performed. Since histological examination
      disclosed meningothelial cells, whorl formation, polymorphism and necrotic
      tissue, she received radiation therapy (total 50Gy) under the diagnosis of
      anaplastic meningioma. On November 10, 1988, she suddenly developed headache,
      nausea, motor weakness and homonymous hemianopia on the left side. CT scan
      revealed intracerebral hemorrhage (ICH) near the region where the meningioma used
      to be. Magnetic resonance image (MRI) demonstrated a high intensity mass at T1
      weighted image and mixed intensity mass at T2-weighted image. Furthermore, there
      were multiple low intensity spotty lesions at the cerebral and cerebellar
      hemisphere in T1 and T2-weighted image. A few parts of these lesions showed
      central high intensity cores and perifocal low intensity areas, which were called
      ring formations or reticulated cores with black rims. The multiple lesions could
      not be detected by CT scan. ICH was evacuated. Histological examination revealed
      no specific pathology except necrotic tissue around the hematoma wall. Diagnosis
      of radiation necrosis was made. On October 25, 1992 she suddenly complained of
      left hemihypesthesia. CT scan demonstrated two high density spotty areas at the
      left caudate head and right thalamus. MRI showed these two lesions as reticulated
      cores with black rims.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7816177
TI  - [Cerebellopontine angle lipoma with vascular anomaly: a case report].
AB  - A case was reported of cerebellopontine angle lipoma with vascular anomaly which
      was thought to be the remnant of fetal anastomosis of the posterior inferior
      cerebellar artery (PICA) and of the anterior inferior cerebellar artery (AICA). A
      42 year-old man had been suffering from intermittent dizziness for a year.
      Worsening of dizziness after mild head trauma led him to visit a doctor who
      pointed out a cerebellopontine angle lesion. On admission to our hospital,
      neurological examination revealed no deficit. Computerized tomography (CT)
      scanning showed a low density mass in the right cerebellopontine angle, which was
      1.5cm in diameter and showed no enhancement with intravenous contrast material.
      The attenuation value on CT of this lesion was--101 Hounsfield units. MRI showed
      a homogeneous mass, which was markedly hyperintense on T1 weighted image and
      proton image, isointense with chemical shift artifact on T2 weighted image and
      markedly hypointense on short TI IR (STIR) image. Signal characteristics on MRI
      were consistent with those of lipoma. Interestingly, MRI demonstrated the cranial
      nerves and vessels penetrating small lesion. The vertebral angiograms revealed
      the anastomosis of PICA and AICA with segmentally hypoplastic vertebral artery on
      the right side and the dilatation of the right distal AICA. Through a right
      suboccipital approach a yellowish mass in the right cerebellopontine angle was
      resected partially (about 50%). Only partial resection was possible because of
      the bleeding from small arteries and the tight adhesion to cranial nerves and
      brain stem. Histological findings of the surgical specimen were consistent with
      those of a lipoma. Postoperative neurological examination showed no neurological
      deficit.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7816178
TI  - [Thoracic outlet syndrome due to first rib anomaly: a case report].
AB  - Compared to cervical rib, first rib anomaly is less familiar to us as a cause of
      thoracic outlet syndrome. We report a case of thoracic outlet syndrome due to
      first rib anomaly. A 50-year-old man was admitted to our hospital because of
      right arm pain when his arm was raised up. Chest X-ray showed an abnormal right
      first rib which made a J-shaped curve and was attached to the second rib. A
      palpable mass was noted in the supraclavicular region. Angiography revealed
      complete occlusion of the right subclavian artery in the Allen test position.
      During conservative therapy for two months, the symptom was gradually getting
      worse. We performed resection of the right first rib and anterior scalenotomy by
      the supraclavicular approach. The patient made a good recovery after the surgery.
      Postoperative angiogram showed no stenotic lesion of the right subclavian artery.
      If a patient has complaints suggesting compression of the subclavian
      neurovascular bundle, we should be careful not to overlook the first rib anomaly
      on chest X-ray.

PMID- 7816179
TI  - [Compression of medulla oblongata by the dissecting aneurysm of the vertebral
      artery 7 years after its rupture: case report].
AB  - A 56-year-old female, who suffered a subarachnoid hemorrhage (SAH) due to
      spontaneous dissection of the right vertebral artery 7 years previously, was
      admitted to our hospital with headache and vertigo. She hadn't had any attacks of
      SAH for 7 years. A magnetic resonance imaging (MRI) showed a high signal
      intensity mass and a low signal intensity due to calcification on the right
      ventrolateral surface of the medulla on both T1 and T2 weighted images. Vertebral
      angiography showed complete occlusion of the cervical segment of the right
      vertebral artery (VA). Left vertebral angiography didn't reveal any retrograde
      filling of the intracranial segment of the right VA through VA union. Thus, the
      spontaneous entrapment by dissection of the vertebral artery was demonstrated 7
      years after SAH with MRI and serial angiography.

PMID- 7816181
TI  - [Dissection of the extracranial vertebral artery: a case report].
AB  - Spontaneous dissection of the vertebral artery is not a frequent occurrence in
      the vertebrobasilar system. The authors show a case with spontaneous dissection
      of the extracranial vertebral artery, which produced recurrent artery-to-artery
      embolism. The angiography revealed characteristic intimal flap. The antiplatelet
      and anticoagulant therapy was able to control ischemic attacks and the patient
      made a good clinical recovery. The angiogram performed two months later showed
      spontaneous resolution of the artery involved. This case shows the effectiveness
      of anticoagulation and antiplatelet therapy for the prevention of artery-to
      artery embolism caused by the extracranial vertebral artery dissection.

PMID- 7816180
TI  - [Traumatic anterior cerebral artery aneurysm difficult to distinguish from
      congenital cerebral aneurysm: case report].
AB  - We report the case of a 29-year-old woman in whom a saccular aneurysm of the
      distal anterior cerebral artery developed following head trauma due to a car
      accident. She was semicomatose on admission but had no lateralizing motor signs.
      Reflexes were symmetrical, with bilateral extensor toe sign. X-ray of the skull
      showed no fracture but CT scans demonstrated a large frontal hematoma and
      interhemispheric bleeding. Initial cerebral angiography performed within 12 hours
      of trauma showed a small protrusion on the pericallosal portion of the left
      pericallosal artery with no branching point nearby. Angiography was repeated on
      the 9th day after admission and confirmed the presence of a saccular aneurysm of
      the pericallosal artery, which had been visible as a small protrusion on the
      initial angiogram. Traumatic aneurysm was suspected and successful neck clipping
      of the aneurysm was performed on the 14th day. Preoperative CT and angiographic
      findings could not rule out a congenital aneurysm but the histological study of
      the specimen confirmed that it was a traumatic false aneurysm. We discussed the
      diagnosis and the etiology of posttraumatic aneurysm.

PMID- 7816182
TI  - [Intracranial foreign body granuloma caused by fine cotton fibers: a case
      report].
AB  - Reported here is a rare case of intracranial foreign body granuloma caused by
      fine cotton fibers originating from the cotton sheet, which was used in the
      previous operation. The patient was a 54-year-old woman who presented with
      headache and right hemiparesis. CT scan demonstrated a large enhanced tumor in
      the left temporal lobe. During the operation, the tumor bled easily and was hard
      to remove. The brain surface was covered with oxidized cellulose (Oxycell) after
      the tumor was subtotally removed. Cotton sheets (Surgical Patty) were also used
      during the operation. The microfibrillar collagen hemostat (Avitene) was not
      applied. The histological diagnosis was astrocytoma. Radio-chemotherapy was
      given. CT and MRI on the 40th day after the operation, showed a large tumor in
      the left temporal lobe, which led to suspicions of tumor recurrence. The second
      operation disclosed a mass which was harder in consistence than the previous one.
      The histological diagnosis was foreign body granuloma, which contained a lot of
      fine cotton fibers. Oxycell was not found in it. The cotton-sheet is well
      documented as a cause of granuloma in the literature, but it is seldom mentioned
      that the foreign body granuloma is caused by cotton fibers, scattered in the
      operative fields. This case report suggests the possibility of cotton-fiber
      granuloma and our simple experiment indicated that a lot of cotton fiber might be
      scattered in the operative fields, if dry cotton sheets are used. These results
      stress that washed cotton sheets should be applied to avoid the possibility of
      the development of cotton-fiber foreign body granuloma.

PMID- 7816183
TI  - [A case of hemangioblastoma in the thalamus].
AB  - Supratentorial hemangioblastoma is encountered very rarely. About 80 cases in all
      have been reported. The authors present a case of supratentorial hemangioblastoma
      in the thalamus with gradually enlarging cysts. The patient was a 45-year-old man
      with complaints of left hemiparesis and headache. Computed tomographic scans of
      the brain showed a cystic mass with mural nodule in the right thalamus. Left
      vertebral angiography demonstrated a vascular tumor fed by a thalamogeniculate
      artery. A right temporo-parietal craniotomy was performed and the tumor was
      totally resected through the transcortical approach. The histological diagnosis
      was hemangioblastoma. Post-operative course was good except for a minor
      complication of the left lower quadrant homonymous hemianopsia and left
      hemiparesis which had disappeared at the time of discharge.

PMID- 7816185
TI  - Current bibliographies of neuropeptides prepared by the University of Sheffield
      Biomedical Information Service.

PMID- 7816184
TI  - [Gene therapy for brain tumors: cytokine gene therapy using DNA/liposome (series
      3)].

PMID- 7816186
TI  - Increased interleukin-2 levels during standard TRH test in man.
AB  - Interleukin-2 (IL-2) is a pluripotential cytokine that, besides its role in the
      regulation of immunocompetent cells function, also stimulates hormone secretion.
      On the other hand, several factors, including cytokines (interleukin-1, IL-1;
      interleukin-6, IL-6) and pituitary hormones (thyrotropin, TSH; prolactin, PRL),
      exert stimulatory effects on T-cell connected IL-2 production. In order to
      evaluate the role of both pituitary hormones in the activation of the immune
      system, the following two standard diagnostic tests were performed: TRH test (0.2
      mg) in 8 healthy human subjects (4F/4M) aged 18-50 years, and oral metoclopramide
      (MCP) test (10 mg) in 8 females with galactorrhea and regular menstruation aged
      18-52 years. The mobilization (peak response) of PRL, TSH, triiodothyronine (T3),
      thyroxin (T4), IL-1 beta, IL-2, IL-6 in TRH test, and PRL, IL-1 beta, IL-2, IL-6
      for MCP test were evaluated. The responses of TSH (2.0 +/- 0.3 vs 12.3 +/- 2.2
      microlU/ml, p < 0.01), PRL (15.3 +/- 2.3 vs 46.4 +/- 8.8 ng/ml, p < 0.01), T3
      (178.0 +/- 16.4 vs 248.7 +/- 21.1 ng/dl, p < 0.001), T4 (7.9 +/- 0.4 vs 9.6 +/-
      0.5 micrograms/dl, p < 0.001), and IL-2 (45.6 +/- 7.8 vs 79.9 +/- 16.4 fmol/ml, p
      < 0.05) in TRH test were noted. The peak response of PRL (16.3 +2- 2.6 vs 107.7
      +/- 22.4 ng/ml, p < 0.01) in MCP test was also observed, but without any changes
      in interleukin concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7816187
TI  - Behavioural effects of two cholecystokinin analogues: JMV 236 and JMV 179.
AB  - The behavioural effects of two cholecystokinin analogues Boc-Tyr(SO3H)-Nle-Gly
      Trp-Nle-Asp-Phe-NH2 (JMV 236), a potent CCK agonist, and Boc-Tyr(SO3H)-Nle-Gly
      DTrp-Nle-Asp-2-Phenylethylester (JMV 179), a CCK antagonist were studied. JMV 236
      (3.125, 12.5 and 50 micrograms/kg i.p.) dose-dependently decreased the
      exploratory activity of rats, the effect being significant for horizontal
      activity (ambulation) at doses of 12.5 and 50 micrograms/kg and for vertical
      activity (rearing) at a dose of 50 micrograms/kg. JMV 179 (3.125, 12.5 and 50
      micrograms/kg i.p.) did not change the horizontal activity but dose-dependently
      decreased the vertical activity, the effect being significant at a dose of 50
      micrograms/kg. JMV 236 administered immediately after training significantly
      facilitated short-term memory in passive avoidance situation but only tended to
      increase the mean latency upon retention testing on the 7th day. JMV 179 tended
      to increase the latency of the passive avoidance response upon retention testing
      at the 24th hour but not on the 7th day after training.

PMID- 7816189
TI  - Activation of the rat melanin-concentrating hormone neurons by ventromedial
      hypothalamic lesions.
AB  - The occurrence of a melanin-concentrating hormone-like peptide (MCH) was
      previously reported in the lateral hypothalamus of the rat. The sequence of this
      peptide was determined but its role as well as its regulation remain unclear. In
      the present study, we examined the effects of minor electrolytic lesions of the
      ventromedial nuclei (VMN) on MCH neurons by using immunocytochemical and in situ
      hybridization procedures. We report that VMN lesions resulted in (1) a clear
      elevation in the number and staining intensity of MCH immunoreactive perikarya
      and fibres, (2) a significant increase in the level of hybridocytochemical signal
      obtained with an oligonucleotide probe complementary to rMCH mRNA. These data
      provide evidence for a role of VMN in modulating the MCH gene a peptide
      expression.

PMID- 7816188
TI  - The cholecystokinin-induced increase in intracellular calcium in AR42J cells is
      mediated by CCKB receptors linked to internal calcium stores.
AB  - Changes in intracellular levels of free [Ca2+]i were monitored in cell
      suspensions and either single cells or cell clusters of the rat pancreatic tumour
      cell line AR42J grown on cover slips. Increases in free [Ca2+]i were seen when
      the bathing medium contained cholecystokinin octapeptide sulphated (CCK) or CCKB
      receptor agonists. Responses to CCK agonists were repeatable and reversed on
      washout. The responses to cholecystokinin and pentagastrin could be blocked by
      selective CCKB receptor antagonists but not a CCKA receptor antagonist. Depleting
      internal Ca2+ stores with thapsigargin blocked the response to pentagastrin
      suggesting that the response was mediated by Ca2+ release from internal stores.
      The rapid run down of the pentagastrin response in the absence of extracellular
      Ca2+ shows that replenishment of internal stores by extracellular Ca2+ is
      important in maintaining the CCK response.

PMID- 7816190
TI  - Identification of thyrotropin-releasing hormone receptor in the rat testis.
AB  - We have recently documented the expression of preprothyrotropin-releasing hormone
      (TRH) gene in murine, human and rat testis. Moreover, we have localized TRH to
      rat Leydig cells immunohistochemically, and found that both prepro TRH mRNA and
      TRH levels are developmentally regulated in the rat testis. To investigate the
      potential roles of TRH in testicular function, characterization of TRH receptors
      (TRH-R) in this tissue was undertaken. Recently, a cDNA encoding murine TRH-R has
      been isolated, making possible cloning of a rat TRH-R cDNA from the anterior
      pituitary gland. This cDNA was used for detection of TRH-R gene expression in the
      rat testis by Northern blot analysis and reverse transcription-polymerase chain
      reaction (RT-PCR). TRH receptor assays were also performed with (3H)MeHisTRH as
      the radioactive ligand. In Northern blot analysis, a single and specific
      hybridization band, approximately 3.8 kb in size, was identified in whole testis
      RNA, identical in size with that found in the anterior pituitary gland. The
      concentration of TRH-R mRNA in the testis was approximately 10% of that in the
      pituitary. TRH-R mRNA was also detected by RT-PCR in Metrizamide gradient
      purified Leydig cells. TRH receptor binding assays revealed the presence of
      specific, high affinity binding sites with a Kd of 1.6 x 10(-8) M in the testis.
      Such TRH binding was inhibited by chlordiazepoxide, a specific antagonist of TRH
      receptor binding. We conclude that TRH may exert local, probably autocrine,
      actions in the testis via a transmembrane receptor very similar or identical to
      that in pituitary.

PMID- 7816191
TI  - Valproic acid-induced rapid changes of met-enkephalin levels in rat brain.
      Probable association with abstinence behavior and anticonvulsant activity.
AB  - Valproic acid (VPA) induces abstinence behavior and analgesia and displays an
      anticonvulsant effect, but its exact mechanism of action is not yet clear. In
      order to view whether proenkephalin derived-peptides are involved in the
      mechanism of VPA-induced behavior, we analyzed immunoreactive-met-enkephalin (IR
      ME) in rat striatum, midbrain, and amygdala 10, 20, and 45 min after i.p.
      injection of 200 mg/kg of VPA. VPA induced body shakes that peaked within 5 to 10
      min. IR-ME increased in the striatum and decreased in the midbrain at 10, 20, and
      45 min, reaching the highest and lowest levels at 10 and 20 min, respectively. No
      changes occurred in the amygdala. Gel filtration chromatography followed by HPLC
      of striatum extracts showed that the increased IR-ME levels corresponded to low
      molecular weight peptides, including ME. These results indicate that VPA produced
      rapid changes of IR-ME levels in rat brain and suggest peptide participation in
      the mechanisms of VPA-induced behavior. The anticonvulsant effect of VPA was
      tested in rats treated with pentylenetetrazol (70 mg/kg) 30 min after VPA (400
      mg/kg) administration, and IR-ME was analyzed in striatum 15 min later. No
      changes in striatal IR-ME levels occurred in protected rats (no behavioral
      convulsions), compared with those treated only with VPA, but a significant
      decrease appeared in unprotected animals (clonic convulsions). These results
      suggest that striatal ME may participate in the mechanism of VPA-induced
      abstinence behavior and in the anticonvulsant effect. Otherwise, midbrain ME
      might be involved in other VPA behaviors such as analgesia.

PMID- 7816192
TI  - Alterations in neurofilament protein immunoreactivity in human hippocampal
      neurons related to normal aging and Alzheimer's disease.
AB  - The distribution of immunoreactivity for the neurofilament triplet class of
      intermediate filament proteins was examined in the hippocampus of young, adult
      and elderly control cases and compared to that of Alzheimer's disease cases. In a
      similar fashion to non-human mammalian species, pyramidal neurons in the CA1
      region showed a very low degree of neurofilament triplet immunoreactivity in the
      three younger control cases examined. However, in the other control cases of 49
      years of age and older, many CA1 pyramidal neurons showed elevated neurofilament
      immunoreactivity. In the Alzheimer's disease cases, most of the surviving CA1
      neurons showed intense labeling for the neurofilament triplet proteins, with many
      of these neurons giving off abnormal "sprouting" processes. Double labeling
      demonstrated that many of these neurons contained tangle-like or granular
      material that was immunoreactive for abnormal forms of tau and stained with
      thioflavine S, indicating that these neurons are in a transitional degenerative
      stage. An antibody to phosphorylated neurofilament proteins labeled a subset of
      neurofibrillary tangles in the Alzheimer's disease cases. However, following
      formic acid pre-treatment, the number of neurofibrillary tangles showing
      phosphorylated neurofilament protein immunoreactivity increased, with double
      labeling confirming that all of the tau-immunoreactive neurofibrillary tangles
      were also immunoreactive for phosphorylated neurofilament proteins.
      Immunoblotting demonstrated that there was a proportionately greater amount of
      the neurofilament triplet subunit proteins in hippocampal tissue from Alzheimer's
      disease cases as compared to controls. These results indicate that there are
      changes in the cytoskeleton of CA1 neurons associated with age which are likely
      to involve an increase in the level of neurofilament proteins and may be a
      predisposing factor contributing towards their high degree of vulnerability in
      degenerative conditions such as Alzheimer's disease. The cellular factors
      affecting hippocampal neurons during aging may be potentiated in Alzheimer's
      disease to result in even higher levels of intracellular neurofilament proteins
      and the progressive alterations of neurofilaments and other cytoskeletal proteins
      that finally results in neurofibrillary tangle formation and cellular
      degeneration.

PMID- 7816193
TI  - Neonatal monocular enucleation-induced cross-modal effects observed in the cortex
      of adult rat.
AB  - The cortices of neonatally enucleated rats were explored for somatosensory
      responses with special reference to an extension into the occipital cortex.
      Monocular enucleation was performed on rats at birth. The animals were raised and
      from the age of three months the activity evoked by either electric stimulation
      of the vibrissa pad or bending of the vibrissae was tested in the contralateral
      cortex by electric recording and autoradiography. It was found that early
      enucleation caused an expansion of the somatosensory responses, among others into
      the visual area. Neurons responsive to visual and somatosensory stimuli were
      demonstrated in the anterior part of the primary and secondary visual areas,
      contralateral to the enucleation. Electrophysiological and autoradiographic
      studies unambiguously proved that early enucleation exerted a significant cross
      modal effect on the somatosensory responsive area.

PMID- 7816194
TI  - Pericruciate fibres to the red nucleus and to the medial bulbar reticular
      formation.
AB  - Extracellular single activity was recorded from pericruciate neurons in
      anaesthetized, paralysed, artificially ventilated cats. A total of 455 neurons
      were classified antidromically according to their sites of termination along the
      corticospinal tract and whether they sent collateral branches to the ipsilateral
      red nucleus and/or to the contralateral nucleus reticularis gigantocellularis. It
      was found that the majority of the branching fibres that reached the most caudal
      segments of the cord were fast conducting, while the slower branching axons
      tended to terminate at more rostral levels of the corticospinal tract. Most of
      the branching fibres terminated at bulbar and cervical levels (153/182: 84%), and
      the remaining ended at thoracic (21/182: 11.5%) and at lumbar (8/182: 4.4%)
      segments of the cord. The non-corticospinal, pyramidal tract fibres branched more
      (56%) than the corticospinal fibres (26.6%). Within the corticospinal neurons,
      the degree of branching decreased with distance along the spinal cord. While
      57.5% of the pericruciate fibres that projected only as far as the pyramidal
      tract were slow conducting, the majority of the corticospinal neurons were fast
      conducting (74.6%). Both pyramidal tract and corticospinal neurons that sent
      branches to one or to the two sites tested were significantly faster conducting
      than the neurons which did not branch. A total of 101 corticorubral and
      corticobulbar neurons which did not respond to pyramidal tract stimulation was
      also recorded. The data can be of significance in the understanding of co
      ordination of different muscles in order to couple movement and posture into a
      common act. The results are discussed from this point of view.

PMID- 7816195
TI  - Evidence for widespread afferents to Barrington's nucleus, a brainstem region
      rich in corticotropin-releasing hormone neurons.
AB  - Supraspinal afferents to the pontine micturition center, Barrington's nucleus,
      were investigated in the rat by visualization of the retrograde tracer, cholera
      toxin subunit B, in neurons following iontophoretic injection into Barrington's
      nucleus. Tissue sections from five rats with injections primarily localized in
      Barrington's nucleus revealed numerous retrogradely labeled neurons throughout
      all rostrocaudal levels of the periaqueductal gray (particularly its
      ventrolateral division), in the lateral hypothalamic area (particularly medial to
      the fornix), and in the medial preoptic nucleus. Retrogradely labeled neurons
      were also consistently found in the nucleus of the solitary tract, in the
      vicinity of the lateral reticular nucleus, nucleus paragigantocellularis,
      parabrachial nucleus, Kolliker-Fuse nucleus, cuneiform nucleus, raphe nucleus and
      zona incerta. In the hypothalamus, in addition to the perifornical region,
      retrogradely labeled neurons were found in all cases in the tuberomammillary
      nucleus, premammillary nucleus, dorsal hypothalamic area, ventromedial
      hypothalamic nucleus, and the paraventricular nucleus. At more rostral levels, in
      addition to the medial preoptic area, retrogradely labeled neurons were seen in
      the bed nucleus of the stria terminalis and in a region just lateral to the
      supraoptic nucleus near the medial amygdaloid nucleus. Retrogradely labeled
      neurons were also observed in the motor, insular, and infralimbic cortices.
      Injections of anterograde tracers (cholera-toxin subunit B or Phaseolus vulgaris
      leucoagglutinin) into the Kolliker-Fuse nucleus, the ventrolateral periaqueductal
      gray, lateral hypothalamic area, or medial preoptic area, resulted in fiber
      labeling within Barrington's nucleus, confirming the retrograde tracing studies.
      As previously reported, numerous neurons in Barrington's nucleus were
      immunoreactive for corticotropin-releasing hormone. Double-labeling studies
      revealed afferent fibers from the periaqueductal gray and lateral hypothalamic
      area overlapping the corticotropin-releasing hormone-immunoreactive neurons of
      Barrington's nucleus, and in some cases anterogradely labeled fibers with
      varcosities appeared to target these neurons. The present results suggest that
      Barrington's nucleus in the rat receives neuronal inputs from brainstem nuclei as
      well as from forebrain limbic structures including hypothalamic nuclei, the
      medial preoptic nucleus, and cortical areas involved in fluid balance or blood
      pressure regulation. In light of the role of Barrington's nucleus in micturition,
      the integration of these various inputs may be important for co-ordinating
      urinary function with fluid and cardiovascular homeostasis. Additionally, as
      neurons in Barrington's nucleus are immunoreactive for the stress-related
      neurohormone, corticotropin-releasing hormone, these diverse inputs may regulate
      stress-related functions of this nucleus.

PMID- 7816196
TI  - Baroreceptor-aortic nerve-mediated release of endogenous L-3,4
      dihydroxyphenylalanine and its tonic depressor function in the nucleus tractus
      solitarii of rats.
AB  - We have proposed that L-3,4-dihydroxyphenylalanine (L-DOPA) is a neurotransmitter
      and/or neuromodulator in the central nervous system [Misu Y. and Goshima Y.
      (1993) Trends pharmac. Sci. 14, 119-123]. This study aimed to explore whether or
      not endogenous L-DOPA, as a neurotransmitter candidate of the primary
      baroreceptor afferents, tonically functions to activate depressor neurons in the
      nucleus tractus solitarii of anesthetized rats. By parallel microdialysis in
      bilateral nucleus tractus solitarii areas, the basal L-DOPA release was in part
      inhibited by tetrodotoxin perfusion (1 microM) or Ca2+ deprivation, and was
      markedly reduced by alpha-methyl-p-tyrosine (200 mg/kg, i.p.), a tyrosine
      hydroxylase inhibitor. Forty to 100 mM K+ concentration-dependently released L
      DOPA. Fifty millimoles K+ repetitively and constantly released L-DOPA. This
      release was Ca(2+)-dependent. Stimulation of the left aortic nerve (100 Hz, 8 V)
      repetitively and constantly released L-DOPA and this release was tetrodotoxin
      sensitive. Phenylephrine i.v. infused produced L-DOPA release and reflex
      bradycardia, temporally associated with a rise and subsequent recovery of blood
      pressure. This release and bradycardia were abolished by denervation of the
      bilateral carotid sinus and aortic nerves. In addition, L-DOPA methyl ester, a
      competitive L-DOPA antagonist, when microinjected into depressor sites of the
      left nucleus tractus solitarii, antagonized depressor responses to mild
      stimulation (20 Hz, 3 V) of the ipsilateral aortic nerve. This antagonist alone,
      microinjected bilaterally, elicited a dose-dependent hypertension, which was
      abolished by alpha-methyl-p-tyrosine. Furthermore, by immunocytochemical analysis
      seven days after denervation of the left aortic nerve, tyrosine hydroxylase- and
      L-DOPA-, but not dopamine- and dopamine-beta-hydroxylase-immunoreactivities
      decreased in the ipsilateral nucleus tractus solitarii and dorsal motor vagus
      nucleus complex area. In the left ganglion nodosum, denervation decreased
      staining and number of L-DOPA-immunoreactive cells and staining of tyrosine
      hydroxylase-immunoreactive cells, but no modification of dopamine-immunoreactive
      cells was seen. Taken together with previous findings that L-DOPA itself is
      stereoselectively responsible for cardiovascular control in this nucleus, it is
      probable that L-DOPA is a neurotransmitter of the primary baroreceptor afferents
      terminating directly in depressor neurons and/or indirectly in some neurons
      within a microcircuit, including depressor neurons of the nucleus tractus
      solitarii. Endogenously released L-DOPA itself tonically functions to activate
      depressor neurons for regulation of blood pressure in the rat nucleus tractus
      solitarii.

PMID- 7816197
TI  - Increased monoamine oxidase B activity in plaque-associated astrocytes of
      Alzheimer brains revealed by quantitative enzyme radioautography.
AB  - The aetiology and pathogenesis of Alzheimer's disease are currently poorly
      understood, but symptomatic disease is associated with amyloid plaques,
      neurofibrillary tangles, neuronal loss and numerous alterations of
      neurotransmitter systems in the CNS. Monoamine oxidase type B is known to be
      increased in Alzheimer diseased brains. The distribution and abundance of
      catalytic sites for monoamine oxidases A and B in post mortem human brains of 11
      Alzheimer disease cases and five age-matched controls were investigated by
      quantitative enzyme radioautography. Using tritiated monoamine oxidase inhibitors
      (Ro41-1049 and lazabemide)--as high affinity substrates selective for monoamine
      oxidases A and B, respectively--it was found that monoamine oxidase B activity
      increased up to three-fold exclusively in temporal, parietal and frontal cortices
      of Alzheimer disease cases compared with controls. This increase was restricted
      to discrete patches (approximately 185 microns in diameter) which occupied
      approximately 12% of the cortical areas examined. In other brain regions
      (hippocampal formation >> caudate-putamen > cerebellum), patches of
      [3H]lazabemide-enriched binding were less abundant. [3H]Ro41-1049 binding (i.e.
      monoamine oxidase A) was unchanged in all tissues of diseased versus control
      brains. The monoamine oxidase B-enriched patches in all cortical regions
      correlated, in their distribution and frequency, with glial fibrillary acidic
      protein-immunoreactive clusters of astrocytes. Diffuse and mature beta-amyloid
      immunoreactive senile plaques as well as patches of high density binding of
      [3H]PK-11195--a high-affinity ligand for peripheral-type (mitochondrial)
      benzodiazepine binding sites in microglia/macrophages--were found throughout
      Alzheimer diseased cortices. The up-regulation of monoamine oxidase B in plaque
      associated astrocytes in Alzheimer's disease--in analogy to its proposed role in
      neurodegenerative disorders such as Parkinson's disease--might, indirectly, be a
      potential source of cytotoxic free radicals. Lazabemide, a selective reversible
      monoamine oxidase B inhibitor, is currently under clinical evaluation for the
      treatment of Parkinson's and Alzheimer's diseases. We conclude that enzyme
      radioautography with [3H]lazabemide is a reliable high resolution assay for
      plaque-associated astroglioses in Alzheimer's disease. Its clinical diagnostic
      utility for positron emission tomography or single photon emission computer
      tomography studies is being investigated.

PMID- 7816198
TI  - Angiotensin II depresses glutamate depolarizations and excitatory postsynaptic
      potentials in locus coeruleus through angiotensin II subtype 2 receptors.
AB  - A previously reported depression of glutamate responses by angiotensin II was
      investigated to define the nature of this neuromodulatory effect. Studies were
      carried out in an vitro brain slice preparation containing the locus coeruleus,
      using intracellular recordings, and iontophoretic, micropressure and bath
      perfusion methods for application of drugs. The angiotensin action was found to
      be blocked by a non-peptide antagonist specific for the angiotensin type 2
      receptor, and not by an antagonist selective for the type 1 receptor. Excitatory
      postsynaptic potentials mediated primarily by excitatory amino acids were also
      depressed by angiotensin II. The angiotensin II depressions of glutamate were
      shown to be strong and highly specific. The low effectiveness of bath-applied
      compared with iontophoretically or micropressure-applied angiotensin II was found
      to be at least partly explained by a rapid degradation by peptidases. Ammonium
      ions and hydrogen ions were also able to depress glutamate responses, but these
      effects were not specific for locus coeruleus neurons and were mediated
      independently of the angiotensin actions. Strong depression by angiotensin II of
      excitatory postsynaptic potentials as well as exogenously applied glutamate
      strengthens the strong possibility of a physiological role for this
      neuromodulatory mechanism. The identification of the type 2 angiotensin receptor
      subtype as the mediator of this effect indicates a novel functional role for this
      receptor, since previously recognized functions of angiotensin II in the brain,
      such as vascular and body fluid regulation, have been associated with the type 1
      receptor.

PMID- 7816199
TI  - Inhibitory and excitatory projections from the dorsal raphe nucleus to neurons in
      the dorsolateral periaqueductal gray matter in slices of midbrain maintained in
      vitro.
AB  - Coronal slices of midbrain from adult rats, maintained in an interface chamber at
      33-35 degrees C, were used to investigate projections from the dorsal raphe
      nucleus to the dorsolateral periaqueductal gray matter. Extracellular recordings
      were made from neurons in the dorsolateral periaqueductal gray matter. The
      majority of cells were silent but activity could readily be induced by
      iontophoretic application of D, L-homocysteic acid from the recording pipette.
      Neuronal perikarya in the dorsal raphe nucleus were activated either by topical
      application of 15-100 nl droplets of 1 or 10 mM D,L-homocysteic acid or by
      iontophoresis into the dorsal raphe nucleus of 0.1 M D,L-homocysteic acid from a
      five-barrelled glass micropipette. Both forms of stimulation evoked increases or
      decreases in firing in neurons in the dorsolateral periaqueductal gray matter.
      The excitatory responses were evoked only from stimulation sites in the dorsal
      subnucleus of the dorsal raphe nucleus, whilst inhibitory responses could be
      evoked by stimulating throughout the nucleus. 5-Hydroxytryptamine was applied by
      iontophoresis to 55 neurons in the dorsolateral periaqueductal gray matter. Of
      these, 89% were inhibited whilst the remaining 11% were excited. No unresponsive
      cells were found. In a second series of experiments anterograde transport of
      biocytin was used to study projections from the dorsal raphe nucleus to the
      periaqueductal gray matter in vitro. Following injections of pellets of biocytin
      into the dorsal subnucleus of the dorsal raphe nucleus, two types of labelled
      axons could be distinguished which had either smooth or beaded profiles. Both
      types of axon could be followed into the region of the dorsolateral
      periaqueductal gray matter, from which recordings were made in the
      electrophysiological experiments. In contrast, following deposits of biocytin
      into the ventral half of the periaqueductal gray matter, very few labelled axons
      were found in the dorsolateral periaqueductal gray matter, although the
      ventrolateral periaqueductal gray matter was heavily labelled. We conclude that
      both excitatory and inhibitory projections from the dorsal raphe nucleus to the
      dorsolateral periaqueductal gray matter are present in the coronal midbrain slice
      preparation. Excitatory projections originate from the dorsal subnucleus of the
      dorsal raphe nucleus and may be mediated by a direct pathway. The inhibitory
      effects evoked from the ventral half of the dorsal raphe nucleus are probably
      mediated indirectly, perhaps by activation of inhibitory interneurons in the
      ventrolateral periaqueductal gray matter.

PMID- 7816200
TI  - Inhibition of sympathetic preganglionic neurons by spinal glycinergic
      interneurons.
AB  - Intracellular and whole-cell patch-clamp recordings were obtained from
      sympathetic preganglionic neurons in rat spinal cord slices. Perfusion of
      selective ionotropic and metabotropic excitatory amino acid agonists induced
      depolarizing responses in all neurons. In approximately 20% of neurons the
      application of these agonists also evoked inhibitory postsynaptic potentials. The
      application of the ionotropic receptor antagonist 6-cyano-7-nitroquinoxaline-2,3
      dione (5-40 microM) blocked the inhibitory postsynaptic potential discharges
      induced by (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (0.5-50
      microM) and N-methyl-D-aspartate (0.5-50 microM), but failed to block the
      inhibitory postsynaptic potentials induced by quisqualate (0.5-50 microM) and
      (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (10-200 microM). Similar
      inhibitory postsynaptic potentials were seen to occur spontaneously or could be
      evoked by electrical stimulation of the dorsal horn. The application of
      tetrodotoxin blocked the spontaneous and evoked inhibitory postsynaptic
      potential, indicating that they result from activity-dependent release of
      neurotransmitter. Strychnine antagonized all inhibitory postsynaptic potentials
      suggesting that they were mediated via glycine receptors. The reversal potential
      of the inhibitory postsynaptic potentials was -65 mV for intracellular and -55 mV
      for whole-cell recordings. This latter value is close to the reversal potential
      for chloride, suggesting that the inhibitory postsynaptic potentials were
      mediated by a chloride conductance. Perfusion of glycine (0.1-1 mM) induced
      inhibitory hyperpolarizing responses in the majority of neurons. This
      hyperpolarizing response was associated with a reduction in neuronal input
      resistance, persisted in the presence of tetrodotoxin, was blocked by strychnine
      and reversed at -55 mV. In some neurons, glycine induced a membrane
      depolarization and increased the rate of spontaneous action potential firing.
      This excitatory effect of glycine was blocked by tetrodotoxin, showed voltage
      dependency and was less sensitive to strychnine than the glycine-induced
      inhibitory response. We conclude from these data that spinal interneurons which
      synapse with sympathetic preganglionic neurons can be activated through multiple
      subtypes of excitatory amino acid receptor, including both ionotropic and
      metabotropic receptors. These interneurons release glycine to evoke inhibitory
      postsynaptic potentials which are mediated via a strychnine-sensitive glycine
      receptor coupled to a chloride conductance.

PMID- 7816201
TI  - Immunologically induced sympathectomy of preganglionic nerves by antibodies
      against acetylcholinesterase: increased levels of peptides and their messenger
      RNAs in rat adrenal chromaffin cells.
AB  - Systemic administration of murine monoclonal acetylcholinesterase antibodies to
      rats has been shown to cause selective degeneration of sympathetic preganglionic
      neurons. In the present study rats were subjected to a single i.v. injection of
      these acetylcholinesterase antibodies, or to normal IgG or saline for control.
      Exophthalmos, piloerection and eyelid-drooping (ptosis) were observed within 1 h
      after administration of the antibodies. Rats were killed at different time-points
      after antibody administration, and the adrenal glands were analysed by means of
      indirect immunohistochemistry and in situ hybridization histochemistry. As soon
      as 3 h after the antibody treatment, a marked increase in the number of
      chromaffin cells expressing mRNA encoding, respectively, enkephalin, calcitonin
      gene-related peptide, galanin, neurotensin and substance P was seen. At 12 h the
      peptide mRNA levels were still elevated and there was a concomitant increase in
      the number of peptide-immunoreactive cells. All peptide levels remained high for
      at least 48 h; however, 77 days after the antibody treatment only enkephalin
      immunoreactive cells could be encountered. A disappearance of
      acetylcholinesterase- and enkephalin-immunoreactive cells could be encountered. A
      disappearance of acetylcholinesterase- and enkephalin-positive fibers was already
      seen 3 h after the antibody treatment, and after 24 h no fibers were encountered.
      In contrast, up until 48 h there was no apparent change in the number or
      intensity of immunofluorescent fibers expressing calcitonin gene-related peptide,
      galanin, neurotensin or substance P. However, 77 days after the antibody
      treatment the number of calcitonin gene-related peptide- and substance P
      immunoreactive fibers was increased as compared to controls. In addition,
      reappearance of acetylcholinesterase- and enkephalin-immunoreactive fibers was
      seen 77 days after antibody administration, although their number was still low
      as compared to controls. Double-labeling immunohistochemistry revealed that the
      chromaffin cells expressing peptides after the antibody treatment preferentially
      were adrenaline storing cells (noradrenaline-negative). The majority of these
      cells expressed only one peptide. Both surgical transection of the splanchnic
      nerve as well as treatment with acetylcholine receptor antagonists mimicked the
      effects seen after the acetylcholinesterase-antibody treatment, although changes
      were less pronounced. The present results show that interruption of splanchnic
      transmission induces fast, marked, and selective increases in peptide expression
      in rat adrenal chromaffin cells.

PMID- 7816202
TI  - Multiple populations of neuropeptide-containing intrinsic neurons in the guinea
      pig heart.
AB  - Recent studies of autonomic ganglia have shown that specific combinations of
      neuropeptides and other potential neurotransmitters distinguish different
      functional types of neurons. In the present paper the patterns of coexistence of
      neurochemicals in guinea-pig cardiac ganglion cells was examined, using multiple
      labelling immunohistochemistry. Many neurons were found to contain somatostatin
      immunoreactivity with various combinations of immunoreactivity for dynorphin B,
      substance P, neuropeptide Y and nitric oxide synthase. There were several small
      populations of neurons without somatostatin immunoreactivity, which contained
      combinations of immunoreactivity for vasoactive intestinal peptide, neuropeptide
      Y, dynorphin B, substance P and nitric oxide synthase. Possible synaptic inputs
      to these populations of ganglion cells were identified using multiple-labelling
      immunohistochemistry combined with long-term organ culture. These experiments
      demonstrated that cardiac ganglia contain prominent pericellular baskets of
      varicose nerve terminals of sympathetic and sensory origin. In addition,
      populations of intrinsic intraganglionic nerve terminals were identified which
      were immunoreactive for vasoactive intestinal peptide, neuropeptide Y or both
      peptides. These terminals presumably originate from intrinsic neurons, with the
      same combinations of neuropeptides, located in other cardiac ganglia. These
      results have demonstrated that there are diverse populations of cardiac ganglion
      cells in the guinea-pig and that some of these neurons may act as interneurons
      within the intrinsic cardiac plexuses. Therefore it is highly likely that vagal
      transmission in the heart is modified by sympathetic, sensory and intrinsic
      neurons and that cardiac ganglia are complex integrators of convergent neuronal
      activity rather than simple relays.

PMID- 7816203
TI  - The ontogeny of [125I]rat-alpha-CGRP binding sites in the spinal cord of sheep: a
      prenatal and postnatal study.
AB  - In this study we describe the ontogeny of [125I]rat-alpha-calcitonin gene-related
      peptide binding sites in the spinal cord of fetal and postnatal sheep. The
      density and distribution of binding sites has been compared with the localization
      of calcitonin gene-related peptide like-immunoreactivity at corresponding stages
      of development [Nitsos I. and Rees S. (1993) Neuroscience 54, 239-252]. At 68
      days of gestation (term = 146 days), the earliest fetal tissue examined, there
      was no evidence of binding sites in lamina I or the outer regions of lamina II
      (lamina IIo), although there was a sparse distribution of binding sites in the
      inner region of lamina II (lamina IIi). By comparison, binding appeared to be
      more marked in laminae III-V and more concentrated again in laminae VI-X. This
      distribution essentially remained constant until 124 days, when there appeared to
      be a marked increase in the density of binding sites throughout the gray matter,
      particularly in the dorsal horn in the lateral extent of both lamina IIo and IIi
      as well as in laminae III, V and VI. This increase was also observed in the
      intermediate zone (lamina VII) and in lamina X. Binding in the ventral horn,
      which was diffuse until this stage, now became particularly dense in the medial
      and lateral regions of the horn. From 124 days to one month postnatal, there was
      no marked change in the density or distribution of binding sites.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7816204
TI  - The neurosteroid tetrahydroprogesterone counteracts corticotropin-releasing
      hormone-induced anxiety and alters the release and gene expression of
      corticotropin-releasing hormone in the rat hypothalamus.
AB  - The ring-A-reduced progesterone derivative 5 alpha-pregnan-3 alpha-ol-20-one
      (tetrahydroprogesterone) is synthesized under normal physiological conditions in
      the brain and is a potent modulator of the GABA receptor. This neurosteroid has
      significant sedative and anxiolytic properties. Corticotropin-releasing hormone
      plays a major role in stress-induced activation of the hypothalamo-pituitary
      adrenal axis, and sustained hyperactivity of hypothalamic corticotropin-releasing
      hormone-producing neurons may be causally related to both, increased pituitary
      adrenal secretion and behavioural symptoms observed in anxiety and affective
      disorders. We investigated the effect of tetrahydroprogesterone on corticotropin
      releasing hormone-induced anxiety, the basal and methoxamine-stimulated release
      of corticotropin-releasing hormone from hypothalamic organ explants in vitro, and
      adrenalectomy-induced up-regulation of the gene expression of corticotropin
      releasing hormone in the hypothalamic paraventricular nucleus in rats. At doses
      of 5 and 10 micrograms i.c.v., tetrahydroprogesterone counteracted the anxiogenic
      action of 0.5 microgram of corticotropin-releasing hormone.
      Tetrahydroprogesterone did not alter the basal release of corticotropin-releasing
      hormone in vitro, but suppressed the stimulatory effect of the alpha 1-adrenergic
      agonist methoxamine on this parameter. Measurements of the steady-state levels of
      mRNA coding for corticotropin-releasing hormone by quantitative in situ
      hybridization histochemistry revealed that tetrahydroprogesterone was equipotent
      with corticosterone in preventing adrenalectomy-induced up-regulation of peptide
      gene expression. Systemic administration of tetrahydroprogesterone also
      restrained adrenalectomy-induced thymus enlargement. These results demonstrate
      that tetrahydroprogesterone has anxiolytic effects that are mediated through
      interactions with hypothalamic corticotropin-releasing hormone in both, genomic
      and non-genomic fashions.

PMID- 7816205
TI  - Neuropeptide Y and behaviorally induced phase shifts.
AB  - Neuropeptide Y-containing fibers project from the intergeniculate leaflet of the
      lateral geniculate nucleus to the suprachiasmatic nucleus. Previous studies have
      indicated that this pathway may be involved in non-photic resetting of the
      circadian clock. Therefore, we investigated the possibility that neuropeptide Y
      mediates phase shifts induced by a particular non-photic stimulus, a pulse of
      running in a novel wheel. Confining hamsters to a small nest box failed to block
      phase shifts induced by neuropeptide Y given at zeitgeber time 4; this indicates
      that increased locomotor activity is not necessary for the observed shifts.
      Antiserum raised against neuropeptide Y or normal serum was administered at
      circadian time 5 through a cannula aimed at the suprachiasmatic nucleus. The
      hamsters were then removed from their cages and placed in a novel wheel for 3 h.
      Hamsters that received normal serum and ran > 5000 revolutions in the novel wheel
      advanced their rhythms (mean shift 2.55 h +/- 0.22 S.E.M.) by amounts similar to
      those of unoperated hamsters. Administration of neuropeptide Y antiserum
      attenuated the shift normally associated with running in a novel wheel (mean
      shift 0.21 h +/- 0.14 S.E.M.). These studies indicate that the neuropeptide Y
      input from the lateral geniculate nucleus to the biological clock is involved in
      the phase shifts seen in response to novelty-induced wheel running. It also
      provides another example of the ability of antisera to alter behavior. This may
      be a useful approach in manipulations of neurochemical activity when antagonists
      are not yet available or poorly defined.

PMID- 7816206
TI  - Voltage dependence of G-protein-mediated inhibition of high-voltage-activated
      calcium channels in rat pituitary melanotropes.
AB  - Dopamine D2 receptor stimulation inhibited high-threshold, slowly inactivating (L
      type) barium currents of isolated, rat pituitary melanotropes in primary culture.
      The extent of inhibition depended on the concentration of LY 171555 applied.
      Current activation in the presence of LY 171555 was described by two time
      constants, a fast one, also observed under control conditions, and a slow one,
      induced by LY 171555. The slow time constant did not depend on the concentration
      of LY 171555. Guanosine-5'-O-(3-thiotriphosphate) (100 microM) induced a similar
      inhibition of the barium currents. Depolarizing prepulses more positive than -20
      mV counteracted the inhibition induced by LY 171555 as well as guanosine-5'-O-(3
      thiotriphosphate). The voltage dependence and time course of this disinhibition
      were obtained. The results suggest that the slow time course of activation during
      current inhibition reflects a voltage-dependent conversion of the channel from
      the inhibited state to an available state. This voltage dependence is probably an
      intrinsic property of the calcium channel. The voltage-dependent rate constants
      of a first-order kinetic model which describes the voltage-dependent inhibition
      and disinhibition were estimated.

PMID- 7816207
TI  - Expression of polysialylated neural cell adhesion molecule by proliferating cells
      in the subependymal layer of the adult rat, in its rostral extension and in the
      olfactory bulb.
AB  - The highly sialylated isoform of the neural cell adhesion molecule is thought to
      be expressed predominantly in the developing nervous system, where it is
      implicated in a variety of dynamic events linked to neural morphogenesis. It has
      become increasingly evident, however, that this "embryonic" neural cell adhesion
      molecule isoform continues to be expressed in certain adult neuronal systems, and
      in particular, in those that can undergo structural plasticity. In the present
      study, we performed light microscopic immunocytochemistry with an antibody
      specific for polysialylated neural cell adhesion molecule and confirmed our
      earlier observations [Bonfanti L. et al. (1992) Neuroscience 49, 419-436] showing
      polysialylated neural cell adhesion molecule-immunoreactive cells in the
      subependymal layer of the lateral ventricle of the adult rat, a region where cell
      proliferation continues into the postnatal period. In addition, we used an
      antibody raised against the proliferating cell nuclear antigen and found that
      proliferating cells continue to be visible in this area, even in the adult.
      Double immunolabeling showed that many of these newly generated cells displayed
      high polysialylated neural cell adhesion molecule immunoreactivity. Cells from a
      portion of the subependymal layer migrate to the olfactory bulb and contribute to
      the continual replacement of its granule neurons [Luskin M. B. (1993) Neuron 11,
      173-189]. We found polysialylated neural cell adhesion molecule-immunoreactive
      cells all along the pathway purported to be followed by the newly generated cells
      to their final destination and in neurons corresponding to granular and
      periglomerular cells in the olfactory bulb. Our present observations thus support
      the contention that polysialylation is a feature of neurons capable of dynamic
      change and may contribute to the molecular mechanisms permitting cell
      proliferation and migration not only during development but also in the adult.

PMID- 7816208
TI  - Distribution of cholecystokinin receptors in the bovine brain: a quantitative
      autoradiographic study.
AB  - Quantitative in vitro receptor autoradiography was used to study the distribution
      of cholecystokin receptors in the bovine brain. [125I]Bolton-Hunter
      cholecystokinin octapeptide binding was described in whole hemisphere sagittal
      and coronal sections using cholecystokinin octapeptide, devazepide and L-365,260
      as competitors to identify the subtypes. High levels of cholecystokinin receptors
      were found in the cortex, where they presented a laminar distribution which
      varied from area to area. The basal ganglia, the caudate nucleus, nucleus
      accumbens and putamen presented high to moderate levels of cholecystokinin
      binding, whereas only very low labelling was found in the globus pallidus.
      Cholecystokinin binding was present in all portions of the bovine hippocampus;
      high levels were found in the dentate gyrus, CA1 subfield of Ammon's horn,
      subiculum and presubiculum. Moderate to high levels were also found in the
      amygdala, inferior colliculus and olfactory tract, while most of the hypothalamic
      and thalamic nuclei exhibited very low or no cholecystokinin binding. Low
      cholecystokinin binding was uniformly distributed across cell layers of the
      bovine cerebellar cortex. Competition of [125I]Bolton-Hunter cholecystokinin
      octapeptide binding in the cortex, nucleus accumbens, caudate nucleus,
      hippocampus, cerebellum and brainstem was much greater in the presence of L
      365,260 than devazepide, thereby suggesting that the majority of cholecystokinin
      receptors in these regions are of the cholecystokinin-B subtype. The results of
      this study, when compared to distribution profiles in other mammalian species,
      provide further evidence for species differences in the distribution of
      cholecystokinin receptors in the brain. The results also support the possible
      interaction between cholecystokinin and dopaminergic systems in areas of the
      brain containing dopaminergic terminals, such as the frontal cortex, nucleus
      accumbens, caudate-putamen and olfactory tubercle.

PMID- 7816209
TI  - Involvement of N- and non-N-type calcium channels in synaptic transmission at
      corticostriatal synapses.
AB  - Calcium channels participate in the events linking axon terminal depolarization
      to neurotransmitter secretion. We wished to evaluate the role of N-type and non-N
      type calcium channels in glutamatergic transmission at corticostriatal synapses,
      since this is a well defined excitatory synapse. In addition, these synapses are
      subject to a variety of forms of presynaptic modulation, some of which may
      involve alterations in calcium channel function. Application of the selective N
      type channel blocker omega-conotoxin GVIA produced an irreversible depression of
      excitatory synaptic transmission in rat neostriatal slices shown by a decrease of
      approximately 50% in the amplitude of the synaptically driven population spike
      during field potential recording and a similar decrease in the amplitude of
      excitatory postsynaptic potentials during whole-cell recording. The component of
      transmission which was resistant to omega-conotoxin GVIA was blocked by omega
      conotoxin MVIIC. omega-Agatoxin IVA had little effect on transmission. Activation
      of a presynaptic metabotropic glutamate receptor depressed transmission to a
      similar extent before and after omega-conotoxin GVIA treatment. Likewise, protein
      kinase C-activating phorbol esters potentiated transmission to the same extent
      before and after omega-conotoxin GVIA treatment. N-type calcium channels appear
      to be crucial for a component of excitation-secretion coupling at corticostriatal
      synapses. A component of transmission involves non-N-, non-L-type high-voltage
      activated calcium channels. The effects of presynaptic metabotropic receptors and
      protein kinase C activation cannot be accounted for solely by alterations in the
      N-type channel function.

PMID- 7816210
TI  - Developmental patterns of somatostatin-receptors and somatostatin
      immunoreactivity during early neurogenesis in the rat.
AB  - The temporal pattern of distribution of somatostatin receptor was investigated
      using the somatostatin analogue [125I]Tyr0-DTrp8-somatostatin14 as a ligand and
      compared with that of somatostatin immunoreactivity during early developmental
      stages in the spinal cord and the sensory derivatives in rat fetuses. Qualitative
      and quantitative analysis showed that somatostatin receptors were detected in a
      transient manner. In the neural tube, they were clearly associated with immature
      premigratory cells and with the developing white matter. During the time-period
      examined (from day 10.5 to 16.5), the disappearance of somatostatin receptors
      followed a ventro to dorsal gradient probably linked to the regression of the
      ventricular zone. In sensory derivatives, they were expressed in the forming
      ganglia and their central and peripheral nerves from embryonic day 12.5 to 16.5
      inclusive, with a peak around day 14.5 and low levels observed at day 16.5.
      Competition experiments performed at embryonic day 14.5 demonstrated that
      somatostatin1-14, somatostatin1-28, and Octreotide displaced specific binding
      with nanomolar affinities while CGP 23996 was only active at micromalar doses.
      Such displacements are compatible with the SSTR2 and/or SSTR4 pharmacology.
      During the time period examined, some transient somatostatin immunoreactive cell
      bodies and fibers were detected in the neural tube and in the sensory
      derivatives. These results demonstrate the existence, in neuronal derivatives, of
      a complex temporal and anatomical pattern of expression of somatostatin
      receptors, from the SSTR2/SSTR4 subtype(s), and somatostatin immunoreactivity. It
      appears that the transient expression of somatostatin receptors and/or
      somatostatin immunoreactivity characterizes critical episodes in the development
      of a cohort of neurons; a fact that unequivocally reinforces the notion that
      somatostatin plays a fundamental role during neurogenesis in vertebrates.

PMID- 7816211
TI  - Methylenedioxymethamphetamine depresses glutamate-evoked neuronal firing and
      increases extracellular levels of dopamine and serotonin in the nucleus accumbens
      in vivo.
AB  - The nucleus accumbens has been implicated as an important site for the actions of
      many drugs that are used recreationally. This study examined the effects of
      methylenedioxymethamphetamine (MDMA), a euphoric and hallucinogenic drug, on
      glutamate-evoked neuronal firing and on extracellular levels of dopamine and
      serotonin in the nucleus accumbens of the rat. Microiontophoretic application of
      MDMA inhibited glutamate-evoked firing of most of the nucleus accumbens cells
      that were tested (83 of 86), as did microiontophoretic application of dopamine
      and serotonin. MDMA-induced inhibition of glutamate-evoked firing was partially
      blocked by the dopamine antagonist SCH39166 and was attenuated by combined
      pretreatment with inhibitors of both serotonin and catecholamine synthesis, p
      chlorophenylalanine and alpha-methyl-p-tyrosine. MDMA applied directly into the
      nucleus accumbens and adjacent regions of the ventral striatum through a dialysis
      probe increased extracellular levels of both dopamine and serotonin. These
      results indicate that MDMA has inhibitory effects on glutamate-evoked neuronal
      firing in the nucleus accumbens and suggest that the inhibition is mediated by
      increased extracellular dopamine and serotonin. Furthermore, these results permit
      MDMA to be added to the extensive list of abused drugs that have been
      demonstrated to elevate extracellular levels of dopamine and serotonin in the
      nucleus accumbens.

PMID- 7816212
TI  - Outflow from the nucleus accumbens to the pedunculopontine tegmental nucleus: a
      dissociation between locomotor activity and the acquisition of responding for
      conditioned reinforcement stimulated by d-amphetamine.
AB  - Output of neuronal information from the nucleus accumbens to the ventral pallidum
      is known to be a critical pathway in the expression of locomotion and incentive
      related behaviour. Some signals from this structure are relayed forward through
      the dorsomedial nucleus of the thalamus to the medial prefrontal cortex, but the
      other major pathway from this site is a descending innervation to the
      pedunculopontine tegmental nucleus. Information carried by these descending
      neurons has been linked with both the output of locomotor activity and incentive
      related information. Previous studies carried out in this laboratory have shown
      no changes in locomotor activity--either spontaneous or in response to systemic
      administration of d-amphetamine or apomorphine--in rats with excitotoxic lesions
      of the pedunculopontine tegmental nucleus. The present experiments compare the
      effects of ibotenate lesions of this nucleus in tests of locomotor activity or
      the acquisition of responding with conditioned reinforcement, following
      injections of d-amphetamine directly into the nucleus accumbens. In general
      agreement with previous results, ibotenate lesions of the pedunculopontine
      tegmental nucleus did not alter locomotion stimulated directly from the nucleus
      accumbens. However, comparable lesions in a group of trained rats produced an
      array of deficits in the conditioned reinforcement paradigm. Most notably, these
      rats directed their attention almost entirely towards pressing the levers
      (practically ignoring the food-hopper panel), but did not appear to be able to
      discriminate between them, while controls focused almost all their efforts on
      pressing the reinforcing lever (virtually ignoring the non-reinforcing lever) and
      the food-hopper panel. These results indicate that pedunculopontine tegmental
      nucleus lesions disrupt an element of reward-related responding, but do not
      affect the production of locomotor activity. This highlights the unlikely
      existence of specific "locomotion-inducing" centres in the mesencephalon and
      implicates the pedunculopontine tegmental nucleus in the formation of stimulus
      reward associations. These data are discussed with respect to a role for the
      pedunculopontine tegmental nucleus in response selection.

PMID- 7816214
TI  - The physiologically induced release of ascorbate in rat brain is dependent on
      impulse traffic, calcium influx and glutamate uptake.
AB  - Extracellular brain ascorbate fluctuates with neuronal activity. There is
      previous evidence that the release of ascorbate is triggered by the re-uptake of
      neuronally released glutamate. This hypothesis predicts that drugs which block
      the release and re-uptake of glutamate will also block the release of ascorbate.
      In the present experiments we have used a novel dialysis electrode which allows
      continuous monitoring of physiologically induced ascorbate release from the
      striatum in freely moving rats. An infusion of the enzyme ascorbic acid oxidase
      abolished the increase in oxidation current in response to tail-pinch, which
      identified it as an ascorbate current. Perfusion with tetrodotoxin reduced the
      response to 25% and with CdCl2 to 4% of control. Perfusion with the uptake
      blocker L-trans-pyrrolidine-2,4-di-carboxylate reduced the response to 24% of
      control. A neuroprotective function for this coupling of ascorbate and glutamate
      release is discussed.

PMID- 7816213
TI  - Ontogeny of D1A and D2 dopamine receptor subtypes in rat brain using in situ
      hybridization and receptor binding.
AB  - The prenatal and postnatal ontogeny of D1A and D2 dopamine receptors was assessed
      by in situ hybridization of messenger RNAs encoding the receptors and by
      radioligand binding autoradiography. On gestational day 14, signals for D1A and
      D2 dopamine receptor messages were observed in selected regions in ventricular
      and subventricular zones which contain dividing neuroblasts, and in intermediate
      zones that contain maturing and migrating neurons. Specifically, D1A and D2
      dopamine receptor message was observed in the developing caudate-putamen,
      olfactory tubercle, and frontal, cingulate, parietal and insular cortices.
      Additionally, D1A dopamine receptor messenger RNA was found in the developing
      epithalamus, thalamus, hypothalamus, pons, spinal cord and neural retina; D2
      dopamine receptor messenger RNA was also observed in the mesencephalic
      dopaminergic nuclear complex. Gene expression of D1A and D2 dopamine receptor
      subtypes in specific cells as they differentiate precedes dopamine innervation
      and implies that receptor expression is an intrinsic property of these neurons.
      The early expression of dopamine receptor messenger RNA suggests a regulatory
      role for these receptors in brain development. While the signal for both messages
      increased in the intermediate zones on gestational day 16, it decreased in the
      ventricular and subventricular zones, and was no longer apparent in these zones
      by gestational day 18. By gestational day 18, abundant D1A or D2 dopamine
      receptor messenger RNA was observed in cell groups similar in location to those
      observed in the adult brain. On gestational day 18, D1A dopamine receptor message
      was noted in the neural retina, anterior olfactory nucleus, the insular,
      prefrontal, frontal, cingulate, parietal and retrosplenial cortices, the
      olfactory tubercle, caudate-putamen, lateral habenula, dorsolateral geniculate
      nucleus, ventrolateral and mediolateral thalamic nuclei, and the suprachiasmatic
      and ventromedial nuclei of the hypothalamus. D2 dopamine receptor message was
      observed on gestational day 18 in the insular, prefrontal, frontal and cingulate
      cortices, the olfactory tubercle, caudate-putamen, ventral tegmental area,
      substantia nigra, and the intermediate lobe of the pituitary. At birth,
      expression of messenger RNA for both dopamine receptor subtypes in the striatum
      approximated that seen in mature rats. In contrast, D1A and D2 receptor binding,
      measured with [3H]SCH-23390 and [3H]raclopride, respectively, was low at birth
      and progressively increased to reach adult levels between days 14 and 21. The in
      situ hybridization data showing early prenatal expression of messenger RNA for
      the D1A and D2 dopamine receptors are consistent with the hypothesis that these
      receptors have a regulatory role in neuronal development.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 7816215
TI  - Exo-endocytotic activity during recovery from a brief tetanic stimulation: a role
      in calcium extrusion?
AB  - Synaptic transmission, metabolism of calcium and ultrastructural changes were
      investigated at the nerve-electroplaque synapse of Torpedo marmorata during and
      after a brief tetanic stimulation. Calcium was found to accumulate in stimulated
      tissue as a function of the number of stimuli; it was subsequently expelled
      during the recovery period. This period was also accompanied by a marked
      hydrolysis of energy-rich phosphates (ATP and creatine phosphate). Histochemical
      localization combined with electron spectroscopic imaging showed calcium deposits
      in synaptic vesicles and in other substructures. The number of synaptic vesicles
      containing a calcium deposit transiently increased at the end of activity and
      declined later during the recovery phase. Rapid cryofixation of the tissue
      followed by freeze-fracturing revealed membrane openings (pits) in the
      presynaptic membrane. The density of pits was low in resting tissue; it did not
      rise during the tetanic stimulation. In contrast, the number of presynaptic pits
      increased significantly soon after, reaching a maximum value at 1 min after
      tetanus. These results are discussed in the light of current hypotheses. They
      suggest that synaptic vesicles play an important role in intraterminal calcium
      homeostasis. The vesicles might sequester calcium ions in synaptic terminals
      during activity and expel them afterwards by exocytosis.

PMID- 7816216
TI  - Exercise-induced upper extremity rhabdomyolysis and myoglobinuria in shipboard
      military personnel.
AB  - During a 6-month Amphibious Task Force deployment to the Mediterranean Sea, five
      sailors and Marines were admitted to the ship's ward with severe upper extremity
      pain, elevated serum muscle enzymes, and a urinalysis dip positive for blood in
      the absence of microscopic hematuria-a finding highly suggestive of
      myoglobinuria. Each patient had begun a vigorous upper-extremity work-out program
      in the ship's weight room 1 to 3 days prior to development of symptoms. All
      responded well to vigorous intravenous hydration, mannitol diuresis,
      alkalinization of the urine, and skeletal muscle rest. No patient developed acute
      tubular necrosis. With increasing emphasis on physical fitness and body building,
      this condition is likely to become more frequent. The most important preventive
      measure is gradual conditioning. Awareness of this entity and early aggressive
      management are necessary to avoid the potentially severe complication of renal
      failure.

PMID- 7816217
TI  - The U.S. Navy Healthy Back Program: effect on back knowledge among recruits.
AB  - This study assessed the immediate effects of the U.S. Navy's Healthy Back Program
      in changing knowledge about back injury prevention. The prevalence of back
      problems among incoming recruits and correlates of back pain also were examined.
      Intervention recruits (n = 1,772) received the Healthy Back Program presentation,
      then completed a questionnaire. Control subjects (n = 1,658) completed an
      identical questionnaire but received no presentation. Intervention recruits
      scored significantly higher on back knowledge (67%) than controls (50%). About
      41% of all recruits had experienced a back problem, 27% reported at least one
      back problem within the past year, and 11% reported back pain during recruit
      training. Lifting, sports participation, and bending were the leading causes of
      previous back problems. Better self-reported health and fitness were associated
      with fewer low back problems.

PMID- 7816218
TI  - Casualties treated during MILCON 92: relevance to training of militia medical
      personnel.
AB  - A brigade field hospital provided the medical support for 2,600 troops during
      MILCON 92 (Militia Concentration 1992). During the exercise, 6.5% of the military
      personnel required treatment. Medical illnesses were far more common than
      traumatic injury. The spectrum of medical and surgical illness treated during
      militia exercises should be used as a guideline for the education and training of
      medical personnel.

PMID- 7816219
TI  - Psychiatric investigation of allegations of child sexual abuse.
AB  - Allegations of child sexual abuse are commonly seen in psychiatric practices.
      While these must be carefully evaluated, false allegations do occur. The syndrome
      of child sexual abuse is reviewed, including prevalence, setting, course, and
      sequelae. Common techniques of clinical investigations are discussed. The uses
      and limitations of interviews, anatomically correct dolls, and drawings are
      reviewed. Providers are encouraged to make thoughtful, informed judgments and not
      to overstate the power of our techniques.

PMID- 7816220
TI  - Heart rate and cardiac arrhythmia during high-Gz flight.
AB  - Twenty-four pilots (age 20-32 years) were monitored with a Holter monitor during
      26 hours including a high-Gz flight in order to evaluate heart rate (HR) and
      cardiac rhythm. Flight experience did not predict the mean in-flight HR (range 69
      121 beats/minute), which decreased with increasing age and correlated to the
      maximum HR during sleep. We recorded maximally 27 ventricular and 97
      supraventricular ectopic beats, 10 junctional rhythms, 5 gray-out, 1 vestibular
      symptom, and 1 instance of numbness of the feet during the flight. No causal
      relationship between HR, cardiac arrhythmia, or symptoms was found. Adaptation to
      in-flight +Gz stress takes place without significant arrhythmia and at a
      submaximal age-related HR.

PMID- 7816221
TI  - FORECAST 2000: a prediction of skills, knowledge, and abilities required by
      senior medical treatment facility leaders into the 21st century.
AB  - This paper reports results from a Delphi study conducted among the Commanders and
      Deputy Commanders for Administration of 37 Army medical treatment facilities
      (MTFs), who identified the most important issues challenging their institutions
      for the remainder of this decade, and the skills, knowledge, and abilities
      required by MTF leaders to deal successfully with those challenges. A Delphi mail
      out was conducted in two iterations. Respondents identified 187 health care
      issues which were divided by content into nine domains by a panel of health care
      experts. The domains, ranked by importance, were cost-finance, health care
      delivery, access to care, quality and risk management, technology, professional
      staff relations, leadership, marketing, and ethics. In the second Delphi
      iteration, MTF leaders agreed upon the necessary skills, knowledge, and abilities
      of future leaders. Results indicated that future leadership will require enhanced
      financial, quantitative, and technical skills, as well as competence in a broad
      array of interpersonal and communication skills. Implications for military
      medical leader development initiatives are discussed.

PMID- 7816222
TI  - Satisfaction with military dental care by active duty soldiers.
AB  - In Fall 1992, a random, worldwide sample of 5,474 enlisted personnel and 4,036
      officers was surveyed on satisfaction with 28 attributes of Army dental care
      using self-administered questionnaires. Simple descriptive statistics for each
      attribute were derived, as was a composite overall satisfaction score using
      factor analysis. Composite scores were regressed on demographics, dental
      utilization, and access barriers to identify those factors that have an impact on
      a soldier's overall satisfaction with Army dental care. Results show above
      average satisfaction with most attributes of Army dental care except access
      attributes. Dental utilization and age exerted a positive impact on overall
      satisfaction; access barriers and assignment to a combat unit had a negative
      impact. The impact of race was mixed. Age had the strongest impact on overall
      satisfaction. Results suggest that improving satisfaction with Army dental care
      must come from improving access. This can be attained only by increasing dental
      manpower and resources.

PMID- 7816223
TI  - Chemoprevention research at the U.S. National Cancer Institute.
AB  - The use of specific chemicals to prevent the development or retard the
      progression of carcinogenesis--known as chemoprevention--is a rapidly growing
      area in cancer research. Developed through the integration of strong laboratory
      and epidemiologic evidence, chemoprevention research has moved successfully into
      the clinical research setting, with diverse agents being tested for their
      efficacy in individuals at high risk of developing certain cancers. The public
      health potential for reducing cancer incidence and mortality through chemical
      intervention provides a unique and promising opportunity, and continued support
      of this multidisciplinary approach to cancer prevention remains a high priority
      for the U.S. National Cancer Institute.

PMID- 7816224
TI  - Starvation and survival: some military considerations.
AB  - The combination of calorie deprivation and forced evasion is a unique and severe
      stress. The physiologic adaptations which occur under these conditions are
      complex. Performance decrements and psychological changes are evident within 24
      hours of cessation of nutritional intake. Although marked losses of both lean
      tissue and total body mass are unavoidable, ultimate survival duration depends on
      many things. This article reviews some of the physiologic and pathologic changes
      which occur during total calorie deprivation and some of the factors which impact
      on the ability to survive.

PMID- 7816225
TI  - Retention rates and retention predictors among graduates of Army Family Practice
      residency programs.
AB  - Accurate career retention rates for the 688 graduates of Army Family Practice
      residency programs over the period from 1973-1990 were determined by
      retrospective cohort analysis. Eight characteristics of these graduates were
      tested by chi-square analysis to determine if they had a predictive effect on
      retention: United States Military Academy attendance (USMA), Uniform Services
      University of the Health Science (USUHS) attendance, fellowship training, prior
      service, gender, first assignment, site of residency training, and spouse with
      history of active duty service. Overall retention was 21%. Significant predictors
      of retention at the p < 0.01 level (chi-square) were (1) USMA attendance, (2)
      USUHS attendance, (3) fellowship training, and (4) prior service. Gender, first
      assignment, and spouse history of active duty service were not factors. The 22%
      of the graduates who had at least one of the four positive predictors form two
      thirds of the present career Family Physician force.

PMID- 7816226
TI  - Retention of internal medicine physicians in the U.S. Army.
AB  - There is currently no reliable information to predict the retention rate of
      internal medicine physicians in the U.S. Army. A retrospective study was
      conducted of internal medicine physicians who had trained in the U.S. Army
      Graduate Medical Education Program during the years 1975-1988. Positive
      predictors for retention included subspecialty training, prior military service,
      and graduation from the U.S. Military Academy or the Uniformed Services
      University of the Health Sciences.

PMID- 7816227
TI  - Lack of association between varicocele and angiokeratoma of the scrotum
      (Fordyce).
AB  - Angiokeratoma of the scrotum is thought to be associated with varicocele. Our
      study population consisted of young soldiers and adult reservists. The young
      population was screened during routine medical examination for the existence of
      varicocele or angiomas on the scrotum, while the adult reservists, who according
      to their medical records had varicocele, were randomly questioned for the
      existence of any kind of spots or lesions on their scrota. We found no
      association between varicocele and angiokeratoma of the scrotum. Since the
      prevalence of varicocele is high, it is possible that in the reported cases the
      association of varicocele and angiokeratoma of the scrotum was coincidental.

PMID- 7816229
TI  - Tank crew vision.
AB  - Army optometrists stationed at The Armor Center, Fort Knox, identify the vision
      conservation needs and the functional visual requirements of each member of the
      tank crew. This article contains recommendations for vision conservation and for
      enhancement of visual function of the tank crewmen.

PMID- 7816228
TI  - Health care delivery in the high-stress environment of chemical and biological
      warfare.
AB  - Understanding health care delivery in high-stress environments, such as the
      chemical and biological warfare (CBW) environment, is important to developing
      better procedures for providing health care to individuals and groups exposed to
      this and other traumas and disasters. Little is known about the behavioral and
      psychological responses affecting health and performance in the CBW environment.
      In this paper, we report preliminary observations of the behavioral and
      psychological responses of a health care delivery exercise occurring over 1 week
      in a simulated CBW environment. Results suggest that responses to the CBW
      environment will include: claustrophobia, difficulties with masks, overheating,
      feelings of having failed, increased risk associated with dedication to the
      group, dehydration secondary to alcohol use, failure to recognize danger, and
      anxiety.

PMID- 7816230
TI  - Dilantin toxicity presenting as mutism following severe head injury: case report.
AB  - A case is presented in which a patient was placed on phenytoin following open
      depressed skull fracture. He subsequently was lost to follow-up, and then
      presented with several complaints, among them mutism, found to be related to
      phenytoin toxicity. There are no reports to date of this condition being caused
      by phenytoin. The issue is again raised of the risk versus benefits of long-term
      anticonvulsant prophylaxis following severe head injury.

PMID- 7816231
TI  - Recurrent erythema nodosum in an aviator.
AB  - Erythema nodosum is an uncommon skin eruption frequently associated with
      underlying infections, systemic diseases, or drug toxicity. We report the case of
      a 27-year-old aviator with three occurrences of erythema nodosum attributed to
      streptococcal pharyngitis. We review the causes of erythema nodosum to emphasize
      the importance of a thorough investigation to rule out serious underlying disease
      prior to returning an aviator to flight status.

PMID- 7816232
TI  - Bomb-related injuries.
AB  - Between 1980 and 1990 there were 12,216 bombing incidents in the United States,
      the majority involving pipe-bomb type devices. Victims of such devices may suffer
      a combination of blast, penetrating, and thermal injuries requiring special
      surgical approaches. A series of cases is presented which illustrates the
      management dilemmas faced in such situations. Given the nationwide incidence of
      bombings, both local emergency medical systems and trauma surgeons should be
      prepared to deal with blast injuries, be aware of their regional incidence of
      bombings, and have a planned response that is coordinated with law enforcement
      agencies.

PMID- 7816233
TI  - [An evaluation of the pulmonary venous flow pattern by transesophageal and
      transthoracic Doppler echocardiography in a normal subject].
AB  - Transesophageal echocardiographic studies have permitted a pulmonary venous flow
      velocity pattern to be identified which is comparable to that recorder using
      invasive methods. The pattern consists of 4 stages: an anterograde systolic flow
      with an early (S1) and late (S2) peak velocity, a diastolic anterograde flow (D)
      and a retrograde flow liked to atrial contraction (Ar). The aim of this study was
      to evaluate the pattern of pulmonary venous flow velocity using transesophageal
      and transthoracic colour Doppler echocardiography in normal subjects in an
      attempt to: 1) determine normal values derived from the pulmonary venous flow
      pattern which may contribute to future studies; 2) find correlations between the
      pattern of pulmonary venous flow and a number of physiological, hemodynamic and
      echocardiographic parameters which take account of the morphological variations
      of this flow pattern within a normal range; 3) demonstrate the possibility of
      being able to carry out study using transthoracic colour Doppler
      echocardiography. The study was carried out in 38 normal subjects aged between 15
      and 76 years old (mean 45 +/- 15) who underwent transthoracic and transesophageal
      colour-Doppler echocardiography. The following parameters were measured: left
      atrium diameter, diameters and telediastolic and telesystolic volumes of the left
      ventricle, ejection fraction and systolic percentage shortening of the left
      ventricle, peak velocity of the mitral flow pattern and the pulmonary venous flow
      pattern. The results obtained show that: 1) the pattern of pulmonary venous flow
      alters with ageing causing the prevalence of systolic over diastolic peak
      velocity; 2) the pulmonary venous flow parameters which appear to be most
      significant in hemodynamic terms are the peak velocities of the early systolic
      flow and anterograde diastolic flow and the ratios S1/S2 and S2/D; 3) the
      echocardiographic parameters most closely correlated with the peak velocity of
      pulmonary venous flow are the dimensions of the left atrium, telediastolic and
      telesystolic ventricular volumes, and the pattern of transmitral flow; 4) heart
      rate does not appear to influence the pulmonary venous flow pattern significantly
      (at least within the range of 50-100 b/min), except for retrograde flow. Similar
      results were obtained using transesophageal and transthoracic Doppler
      echocardiography and therefore if future studies succeed in obtaining useful
      information, of not only speculative but also practical interest, from the
      evaluation of pulmonary venous flow, these can be obtained using a simple,
      widespread and completely non-invasive method such as transthoracic Doppler
      echocardiography.

PMID- 7816234
TI  - [Stenotic-obliterative carotid lesions and arterial hypertension. An analysis of
      16,379 subjects from the OPI program. Obiettivo Prevenzione Ictus].
AB  - BACKGROUND: A positive correlation of arterial hypertension (AH) to
      atherosclerosis and of AH to cerebral stroke is widely accepted, while the
      relationship between AH and carotid occlusive disease (COD) is not yet clear.
      PURPOSE: To assess the correlation of AH to COD in a resident population screened
      during the OPI (Obiettivo Prevenzione Ictus) program. METHODS: The goals of OPI
      program are to assess prevalence of COD among the population resident in the USSL
      (Sanitary District) n. 69 Lombardia (Parabiago-Italy), aged 45 to 75; to
      administer a therapeutic protocol; and to carry on a long-term follow-up of
      people treated for risk of stroke from COD. Data reported herein were recorded
      from the first 16,379 subjects out of 24,436 enrolled in the OPI program and
      classified according to blood pressure and degree of COD (preliminary report).
      All were investigated by physical examination and CW Doppler ultrasound; subjects
      suspected to harbor COD of any entity underwent a second physical examination and
      color coded echoflow imaging of extracranial carotid arteries, to assess the
      degree of COD. Statistical analysis has been performed through Fisher's exact
      test and chi 2 test, and results were assumed as significant for a p value of
      less than 5 x 10(-2). RESULTS: Among 7,800 males and 8,779 females, some 8,428
      (51.45%) people were shown to be hypertensive: 2,800 of them were classified as
      borderline (e.g.: systolic pressure of 141-160 mmHg and diastolic < 90 mmHg). As
      many as 538 COD were observed in 404 subjects. Among the 7,951 normotensive
      people as many as 109 COD (20.3%) were identified in 90 subjects (1.12%); among
      hypertensive people, 314 (3.72%) were affected with 429 (79.7%) COD (p < 10(-6)):
      COD prevalence among borderline hypertensive subjects was double than among
      normotensive (p = 1.3 x 10(-6)). Unilateral as well as bilateral CODs were more
      frequent among hypertensive people (p between 3.1 x 10(-2) and < 10(-6) according
      to the degree of stenosis). Forty-five (50%) among 90 normotensive people
      affected with COD showed unilateral stenosis < 50%, but only 19 (14.2%) among 134
      affected with bilateral lesions were normotensive, and 81.6% of these lesions
      were < 50%. Among 230 lesions in 115 hypertensive people with bilateral COD, 137
      (59.5%) were < 50%, 63 (27.4%) between 50-70%, 19 (8.3%) > 70%, and 11 (4.8%)
      occlusions. CONCLUSIONS: COD is more frequent among hypertensive than
      normotensive people (odds ratio = 3.38; p < 10(-6)). Severity of COD is higher in
      hypertensive subjects (odds ratio = 3.79; p < 10(-6)). Isolated systolic
      hypertension is more frequently associated to COD than systolic-diastolic
      hypertension (odds ratio = 2.26; p < 10(-6)). Among people with isolated systolic
      hypertension, diastolic values of less than 75 mmHg do not increase the risk of
      COD. As COD prevalence is concerned, the 1,494 subjects with effective drug
      control of hypertension behaved as like as people with isolated systolic
      hypertension: in particular, the risk of COD was 7.59 times as high as for
      normotensive people.

PMID- 7816235
TI  - [Renal arteriovenous fistulae].
AB  - Arteriovenous fistulas (AVFs) involving the kidney are rare. They are generally
      classified as congenital, idiopathic or acquired. The authors present 5 cases of
      renal arterio-venous communications observed in recent years. These cases don't
      include the congenital type and represent the forms of AVFs that are more
      frequently observed (1 idiopathic, 3 iatrogenic, 1 associated with malignancy).
      This study is aimed at examining the clinical picture and the procedures of
      detection and monitoring of renal AVFs. The various adopted therapeutic
      procedures (nephrectomy, surgical ablation, radiological embolization) are
      analyzed.

PMID- 7816236
TI  - [Esthetic suture of the lower limbs after a saphenous vein graft in cardiac
      surgery. Polydioxanone vs Vicryl].
AB  - The vena saphena magna is widely used as a passage during myocardial
      revascularisation surgery (CABG). The preparation of the vein involves a long
      incision on the thigh and leg which is routinely closed using a continuous suture
      thread in Vicryl of the subcutis and continuous intradermal suture of the cutis.
      The authors retrospectively evaluated the functional and esthetic results of
      intradermal suture performed using two different types of reabsorbable thread:
      PDS II and Vicryl. A total of 178 patients underwent CABG surgery at the Heart
      Surgery Division of Tor Vergata University of Rome during the period January
      September 1992. Mean age was 63 year +/- 7 (SD), 140 were males and 38 females.
      PDS II 3/0 was used for intradermal suture in 88 patients, whereas Vicryl 3/0 was
      used in 90. There were no significant differences between the two groups with
      regard to age, sex, number of grafts, associated pathologies or wound length.
      After 1-9 months (mean 5.6 months) the surgical wound on the saphenectomized limb
      was evaluated. It was found that compared to Vicryl the use of PDS II presented a
      higher incidence of keloids (p > 0.05). This was probably due to the greater
      reaction provoked in the dermis by the monofilament compared to twisted thread.
      The authors conclude that the use of a reabsorbable twisted thread, such as
      Vicryl or Vicryl Rapid, is preferable owing to the higher rate of compliance and
      lower incidence of complications.

PMID- 7816237
TI  - [The antihypertensive effects of the lisinopril-hydrochlorothiazide combination
      (Zestoretic) in elderly hypertensive patients. The results of a multicenter
      study. The Italian Zestoretic Study Group].
AB  - The present study was aimed at evaluating the effects of combined lisinopril
      hydrochlorothiazide (Zestoretic) antihypertensive treatment on sphygmomanometric
      and 24-hour systolic and diastolic blood pressure values in 631 elderly patients
      (mean age +/- SD 68.8 +/- 5.8 years) with mild-to-moderate essential systolic
      diastolic or isolated systolic hypertension. After a wash-out period of 4 weeks,
      patients received o.d. lisinopril combined with hydrochlorothiazide for a 6-week
      period. At the end of both periods, sphygmomanometric blood pressure was assessed
      24 hours after dosing and 24-hour ambulatory blood pressure was performed, taking
      blood pressure readings every 15 minutes during day- and night-time. The drug
      induced in all elderly hypertensives clearcut and significant systolic and
      diastolic blood pressure reductions (average reduction amounting to 25 mmHg and
      15 mmHg for systolic and diastolic blood pressure values respectively) without
      any significant heart rate change. The antihypertensive effect of combined
      lisinopril and hydrochlorothiazide was significant during the whole 24-hour
      monitoring period. This antihypertensive drug regimen was well tolerated, a low
      side effect profile being observed (10.3% of treated patients). Thus single daily
      administration of combined lisinopril-hydrochlorothiazide represents a safe and
      effective antihypertensive drug regimen.

PMID- 7816238
TI  - [Infectious endocarditis following artificial insemination. A clinical case
      report and review of the literature].
AB  - We describe a case of infective endocarditis in a 33 year old patient, with
      mitral valve prolapse (MVP), who underwent nine attempts of artificial
      insemination with semen by donor. Several blood cultures demonstrated the
      presence of Enterococcus faecalis; the same agent was identified in some vaginal
      cultures. Despite antibiotic therapy, infective endocarditis was complicated by
      severe mitral regurgitation, followed by the rupture of a chorda tendinea. The
      patient underwent cardiac surgery: valvuloplasty of posterior mitral cusp,
      chordae tendineae in Goretex and anulus reinforcement with autologous
      pericardium. MVP is the most common heart disease associated with infective
      endocarditis in non-drug addict patients (32-54%). The review of the literature
      did not show any other case of infective endocarditis after artificial
      insemination procedures. Because of the large spread of these procedures, we
      think antibiotic prophylaxis of infective endocarditis should be considered in
      patients with MVP.

PMID- 7816239
TI  - [Brachial artery stenosis in a subject with a past traumatic fracture of the
      elbow].
AB  - We report a case of elbow fracture associated with brachial artery stenosis.
      Several authors reported that elbow fractures are associated with brachial artery
      injury. In the present case we detected brachial artery stenosis in a patient
      with a history of elbow fracture. Therefore we suggest that every patient with
      elbow trauma should undergo an assessment for brachial artery stenosis.

PMID- 7816240
TI  - [Emergency aneurysmectomy for persistent ventricular tachycardia].
AB  - Aneurysms are a later consequence of acute myocardial infarction, developing in
      about 20% of patients with transmural infarcts. Pathologically aneurysms have two
      general forms: the first type has large endocardial fibroelastosis overlying the
      infarct size, the second type contains little or no endocardial fibroelastosis
      but often contains a large amount of mural thrombus. These pathologic types
      correlate with clinical complications. The first type is related to recurrent
      sustained ventricular arrhythmias, the second type to systemic embolism. The
      importance of endocardial pathology in pathogenesis of ventricular: arrhythmias
      is also suggested by recent endocardial stripping procedures. We report the case
      of a patient 63 years old, with ischemic left ventricular aneurysm complicated
      with multiple morphologic sustained ventricular tachycardia resistant to drug
      treatment. Standing hemodynamic shock and anginal symptoms, was performed left
      ventricular aneurysmectomy in state of emergency. The surgical treatment was
      successful. A programmed ventricular stimulation prior to hospital discharge, not
      induced ventricular tachycardia, also Holter monitoring was normal. The patient
      was discharged after 18 days. After 4 months he is well, and no arrhythmia was
      demonstrated during ambulatory controls.

PMID- 7816241
TI  - [An allergic reaction due to i.v. urokinase administration].
AB  - We notify a case of anaphylactic reaction due to urokinase which was administered
      to a patient with extended anterior acute myocardial infarction. He showed some
      allergic reaction symptoms such as: cutaneas eritema and dyspnea with bronchial
      spasm which disappeared with an intravenous cortisone drug. Therefore we think
      that urokinase too might give rise to anaphylactic reaction.

PMID- 7816242
TI  - Cures for polycystic kidney diseases?

PMID- 7816243
TI  - Endothelial cell antibodies: pathogenetic or epiphenomenon?

PMID- 7816244
TI  - Angiotensin II type II receptor. Does it have a role in the normal or diseased
      kidney?

PMID- 7816245
TI  - Unsatisfactory control of serum phosphate: why is it so common and what can be
      done?

PMID- 7816246
TI  - Medical management of renal hyperparathyroidism. Pulse treatment with vitamin D
      metabolites or not?

PMID- 7816247
TI  - End-stage renal failure due to analgesic nephropathy, its changing pattern and
      cardiovascular mortality. EDTA-ERA Registry Committee.
AB  - The changing pattern of prevalence and age distribution of analgesic nephropathy
      as a cause of end-stage renal failure (ESRF) in patients on RRT was analysed
      using the EDTA-ERA Registry's files. Comparing 1990 to 1981, the percentage of
      patients with analgesic nephropathy decreased in many European countries and the
      Registry's average came down from 3 to 2%. The highest prevalence was noted for
      Switzerland, which showed a decrease from 28 in 1981 to 12% in 1990. During the
      same interval the age distribution shifted to the right with an increase in
      median age from 57 to 63 at start of RRT for analgesic nephropathy. In
      Switzerland the age-specific acceptance rate to RRT for patients with analgesic
      nephropathy decreased to less than 1/3 in the age cohorts below 55 but increased
      in those aged 65 or older. This increase in the elderly cohorts appeared to be
      related to the growing acceptance rate to RRT of elderly patients in general
      rather than to an increasing incidence of ESRF due to analgesic nephropathy.
      Mortality in general and death rates due to cardiovascular causes were found not
      to differ in RRT patients with analgesic nephropathy from that of other standard
      primary renal diseases (excluding diabetic nephropathy and systemic diseases).
      Some 20 years after withdrawal of phenacetin from the analgesic market, analgesic
      nephropathy all but disappeared as a cause of ESRF in Sweden and Denmark, and the
      same may be expected to occur in countries like Switzerland, Belgium, and others
      in the not too far distant future.

PMID- 7816248
TI  - Trends in incidence of end-stage renal failure in Australia, 1972-1991.
AB  - Age-specific and cumulative incidence rates were calculated for entry into
      Australian end-stage renal failure programmes from 1972 to 1991, as a result of
      all causes, or from analgesic nephropathy, glomerulonephritis, hypertension and
      vascular disease, or diabetes. Three different trends were demonstrated. A rising
      recorded incidence of renal failure occurred throughout the period of observation
      in those aged 0-4 years (all causes) and in those aged 55 years and over (all
      categories, least in analgesic nephropathy) principally attributable to a falling
      fraction of patients not accepted for treatment. Falling incidence rates
      indicating a real reduction in the burden of disease were seen for analgesic
      nephropathy (at least up to the age of 64 years) and hypertension and vascular
      disease (only up to the age of 54 years). In young adults the unchanging
      incidence of renal failure due to all causes, glomerulonephritis and diabetes
      probably reflect nearly complete acceptance rates into end-stage renal failure
      programmes, and therefore approximate the true burden of disease. In end-stage
      renal failure, age-specific or age-standardized cumulative rates are required to
      distinguish rising or falling incidence of disease from trends due to changing
      medical practice.

PMID- 7816249
TI  - Renal functional reserve in experimental chronic glomerulonephritis.
AB  - Loss of renal functional reserve, that is, absence of the glomerular vasodilatory
      response to amino-acid infusion, has been interpreted as equivalent to glomerular
      hyperperfusion/hypertension, and therefore proposed as a marker of high risk for
      progressive glomerular sclerosis. To substantiate the validity of this hypothesis
      we evaluated the renal response to glycine and the extent of glomerular damage 10
      12 weeks after induction of anti-glomerular basement membrane glomerulonephritis
      with or without superimposed clip hypertension. Untreated rats and rats
      chronically treated with quinapril, a converting-enzyme inhibitor, were studied.
      In untreated groups, loss of renal functional reserve was demonstrated since GFR,
      single-nephron GFR (SNGFR) and plasma flow (SNPF) did not increase during glycine
      infusion. The absence of renal reserve was associated with glomerular
      hyperfusion/hypertension, and development of proteinuria and glomerulosclerosis.
      Quinapril reduced proteinuria and diffuse sclerosis in anti-glomerular basement
      membrane GN, and decreased blood pressure and segmental glomerulosclerosis in
      antiglomerular basement membrane GN with superimposed clip hypertension. Both
      treated groups demonstrated a restoration of renal functional reserve, as
      depicted by increases in GFR, SNGFR, and SNPF after glycine, despite persistence
      of glomerular hyperperfusion/hypertension. These data demonstrate that renal
      functional reserve testing, although it does not detect glomerular
      hyperperfusion/hypertension, can provide information on the progression of
      glomerular damage.

PMID- 7816250
TI  - Inhibition of growth by calcitriol in a proximal tubular cell line (OK).
AB  - Calcitriol has been shown to inhibit (i) cell proliferation of renal carcinoma
      cell lines and of cultured adult human mesangial cells in vitro, and (ii) renal
      compensatory growth in vivo. In the present study we examined the effects of
      calcitriol on DNA synthesis and cell replication in an immortalized cell line
      showing the phenotypic characteristics of proximal tubular cells (opossum kidney,
      OK cells). The viability of OK cells was not affected by calcitriol (Trypan-blue
      exclusion, LDH and K+ release), but the cells did not convert 3H-25(OH)2D3 to 3H
      1,25(OH)2D3. In the log growth phase, calcitriol (but not alternative vitamin D
      metabolites) caused dose-dependent (10(-12) to 10(-6) M) inhibition of
      radiothymidine incorporation. Inhibition was calcium dependent, i.e. it was more
      pronounced at the lower nominal calcium concentration in tissue culture media
      (0.9 versus 1.8 mmol/l) and amplified by coincubation with nifedipine (1 microM).
      Inhibition of DNA synthesis was paralleled by inhibition of cell replication
      (growth curve) under basal conditions and after stimulation with EGF (10 ng/ml).
      In conclusion, calcitriol inhibits proliferation of proximal tubular cells which
      normally express 1-alpha-hydroxylase activity.

PMID- 7816251
TI  - Experimental diabetic renal growth: role of growth hormone and insulin-like
      growth factor-I.
AB  - We have compared the kidneys of two inbred strains of rats (Lewis and Lewis
      Dwarf) 7 days after the induction of diabetes mellitus with streptozotocin, in
      order to examine the influence of a selective growth hormone (GH) deficiency on
      diabetic renal growth and insulin-like growth factor-I (IGF-I) content of the
      kidneys. Insulin-like growth factor-I (IGF-I) content of the kidneys. Insulin
      like growth factor-I was measured by radioimmunoassay and its distribution within
      the kidney by immunohistochemical staining. We detected a significant increase in
      both the wet weight (32.9 +/- 5.3%, P = 0.0085) and dry weight (16.3 +/- 6.3%, P
      = 0.046) of the kidneys of diabetic Lewis rats but dwarf rats, selectively
      deficient in GH, did not show a significant increase in either parameter.
      Extractable IGF-I increased within the kidneys of diabetic rats of both strains
      but to a lesser extent in the dwarf rats (+105 +/- 28% and +65 +/- 21%
      respectively, P < 0.01). In diabetic Lewis rats a positive correlation was noted
      between the severity of glycaemia and kidney IGF-I content (r = 0.604, P < 0.05)
      but no such correlation was noted in dwarf rats. Inulin-like growth factor-I
      immunostaining increased in diabetic rats of both strains, mainly within cells of
      the thick ascending limb of the loop of Henle including damaged and vacuolated
      cells. However, morphometric analysis of the staining showed that it was
      significantly less widespread in the diabetic dwarf rats (P = 0.026).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7816252
TI  - Duodenal calcium binding protein and active calcium transport in rats: are they
      functionally related?
AB  - The effects of calcitriol and a novel calcitriol analogue, 22-oxacalcitriol (OCT)
      on duodenal Ca transport, calbindin-D9k mRNA, and calbindin-D9k content were
      studied in two animal models reflecting common human pathologies, namely arterial
      hypertension and chronic renal failure, as well as in normal rats. The hormone or
      its analogue were administered intraperitoneally to vitamin-D-replete rats.
      Active Ca transport was increased in both spontaneously hypertensive rats (SHR)
      and in normotensive control WKY rats 5 h after calcitriol dosing of either 60 and
      600 ng per rat. In WKY, calbindin-D9k content was slightly increased after the
      injection of 60 ng calcitriol, but not of 600 ng calcitriol whereas calbindin-D9k
      mRNA stayed essentially unchanged. In contrast, active Ca transport was
      significantly stimulated after the higher dose of 600 ng calcitriol. In SHR,
      while both doses of calcitriol increased active Ca transport, they had no
      stimulatory effect on calbindin-D9k mRNA or protein. In chronically uraemic rats,
      active Ca transport, duodenal calbindin-D9k and calbindin-D9k mRNA were
      stimulated after the injection of two subsequent doses of 300 ng calcitriol per
      rat. OCT treatment at same dosage led to a similar stimulation of calbindin-D9k
      and calbindin-D9k mRNA, but failed to induce an increase in active Ca transport.
      These results show that the stimulation of intestinal active Ca transport and
      calbindin-D9k can be entirely dissociated at the protein synthesis and the mRNA
      expression level (1) after calcitriol administration to normal and hypertensive
      rats, and (2) after OCT administration to uraemic rats.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7816253
TI  - De-novo COL4A5 gene mutations in Alport's syndrome.
AB  - Before the advent of direct molecular gene analysis the diagnosis of Alport
      syndrome was operationally based on three of the four classical clinical
      criteria. Recently, mutations have been identified in the COL4A5 gene, which is
      involved in X-linked Alport syndrome. Here we describe two de-novo mutations in
      two unrelated children, a male and a female, both with early onset of the
      nephropathy, but with only one of the diagnostic criteria, i.e. electron
      microscopy alterations. Because of the significant estimated proportion of de
      novo mutations this diagnosis should be considered in children with early signs
      of nephropathy, even without a suggestive family history or clinical picture
      (ocular or audiologic abnormalities). In the future the diagnosis of Alport
      syndrome will probably be made on the basis of both clinical findings and
      molecular analysis. Now Alport syndrome is clearly underdiagnosed.

PMID- 7816254
TI  - Myofibroblasts, predictors of progression of mesangial IgA nephropathy?
AB  - The limited knowledge of the cellular mediators of renal scarring hampers
      progress in the management of progressive chronic renal failure (CRF). We have
      studied 38 patients with biopsy-proven mesangial IgA nephropathy with emphasis on
      attempting to define the role of myofibroblasts (alpha-smooth muscle actin/SMA
      positive cells) in renal scarring. In 18 untreated patients, correlations were
      undertaken between known histological parameters of progression as well as the
      presence of myofibroblasts in tissues and the clinical outcome. alpha-SMA
      staining by an avidin-biotin-peroxidase method was confined to a large extent to
      the vascular smooth muscle cells of normal kidneys but extended to the
      tubulointerstitium and periglomerular space in scarred kidneys. Mild glomerular
      staining was also noted. The interstitial immunostain followed a similar
      distribution to that of interstitial type III collagen. Morphometric analysis
      showed the interstitial alpha-SMA staining to be a reliable histological
      predictor of outcome as it discriminated between progressors and non-progressors
      (chi 2 = 4.923, P = 0.026). The intensity of the interstitial alpha-SMA staining
      correlated with renal functional outcome; inversely with the reciprocal of serum
      creatinine slopes (r = -0.466, P < 0.025) and positively with the serum
      creatinine value at the end of the observation period (r = 0.704, P <
      0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7816255
TI  - Renal replacement therapy in cryoglobulinaemic nephritis.
AB  - Seventeen patients with nephritis due to mixed cryoglobulinaemia were submitted
      to regular haemodialysis in 11 and continuous ambulatory peritoneal dialysis in
      six after 145 +/- 55 months from the onset of the disease. Four patients with
      very poor clinical conditions died within 6 months from the beginning of
      dialysis. The other 13 patients were followed for a mean period of 78.7 +/- 41.6
      months. The actuarial survival rate was 65% at 5 years. Both clinical and
      immunological signs of mixed cryoglobulinaemia reduced during dialysis but a long
      lasting burn out was observed only in one patient. Two patients received a kidney
      graft. Mixed cryoglobulinaemia nephritis recurred in both of them respectively 5
      and 10 months after transplantation. One patient lost his graft 13 months after
      transplantation because of chronic rejection. The other one still has a
      functioning kidney 48 months after renal transplantation. The life expectancy
      with dialysis for mixed cryoglobulinaemia patients is similar to that of patients
      with standard primary renal disease but some few patients with severe disease at
      the beginning of dialysis have a poor prognosis. Nephritis may recur after renal
      transplantation but this does not preclude per se a favourable course in the long
      term.

PMID- 7816256
TI  - Treatment of aluminium intoxication: a new scheme for desferrioxamine
      administration.
AB  - In order to control aluminium toxicity in dialysis patients it is preferable to
      prevent or limit exposure to it. However, it is sometimes necessary to remove the
      aluminium by the use of appropriate techniques. The collateral effects of
      desferrioxamine have led us to test new forms of administering desferrioxamine
      and attempt to reduce the dose. The aim of this study was to compare the removal
      of aluminium by administration of 15 mg/kg of desferrioxamine under two different
      schemes, that is, 44 h before the dialysis (classic scheme) and 1 h before
      dialysis (new scheme). The study was carried out in 10 patients over a period of
      4 weeks. Aluminium removal was quantified in the dialysate throughout the
      dialysis. Measurement was also performed of the serum aluminium changes that
      occurred during the study. The total removal of aluminium was determined over
      three consecutive dialysis sessions following the administration of
      desferrioxamine. A similar amount of aluminium was found under both schemes.
      However, in the case of those patients given desferrioxamine 1 h prior to
      dialysis, removal of aluminium induced significantly lower serum aluminium peaks:
      (P < 0.02). These results suggest that the administration of desferrioxamine 1 h
      before dialysis is a valid alternative to the classic scheme (44 h before). The
      removal of aluminium at lower increments in the serum aluminium entails less risk
      for patients.

PMID- 7816257
TI  - Interleukin-8 in chronic renal failure and dialysis patients.
AB  - A total of 105 patients participated in this study, including 10 with chronic
      glomerulonephritis with normal renal function (CGN patients), 36 uraemic patients
      (CRF patients), 19 continuous ambulatory peritoneal dialysis patients (CAPD)
      without peritonitis, three CAPD patients with peritonitis, 37 patients undergoing
      chronic haemodialysis (HD) divided into short-term HD, 15 patients; medium-term
      HD, 12 patients; and long-term HD, 10 patients. IL-8 and two other
      proinflammatory cytokines, IL-6 and TNF alpha were tested using a specific
      immunoassay. IL-8, IL-6, and TNF alpha serum levels were significantly increased
      in patients with chronic renal failure compared to their levels in normal
      individuals (P < 0.0001, P < 0.05 and P < 0.0001 respectively). The most
      pronounced increment in IL-8, IL-6 and TNF alpha serum levels was observed in
      CAPD patients (P < 0.0001). CAPD patients without peritonitis showed relatively
      low levels of IL-8 or IL-6 in peritoneal dialysate effluents (PDE), whereas PDE
      TNF alpha were not detectable in almost all patients tested. Patients with
      peritonitis showed very high serum and PDE levels of IL-8, IL-6 and TNF alpha.
      The clinical recovery from peritonitis was characterized by a rapid fall in IL-8,
      IL-6 and TNF alpha in serum and dialysate. HD patients showed a significant
      increase in serum levels of IL-8 and also IL-6 and TNF alpha compared to normal
      individuals (P < 0.05, P < 0.05 and P < 0.01 respectively).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7816258
TI  - Ten years experience of CAPD in diabetics: comparison of results with non
      diabetics. Italian Cooperative Peritoneal Dialysis Study Group.
AB  - CAPD outcomes were compared between a group of 301 diabetic patients (mean age +/
      SD, 58.9 +/- 12.7 years, 55.8% males) and a group of 1689 non-diabetic patients
      (mean age +/- SD 57.8 +/- 14.8 years, 55.9% males) treated in 30 centres
      participating in the Italian Cooperative Peritoneal Dialysis Study Group from
      1980 to 1989, with follow-up observation periods of 444 years (mean +/- SD, 1.48
      +/- 1.24) and of 3502 years (mean +/- SD, 2.07 +/- 1.91) respectively. CAPD was
      the first modality for 87.2% of diabetics and 78.1% of non-diabetics (P < 0.001).
      The percentage of patients who needed a partner for CAPD was 45.9% in diabetics
      and 30.2% in non-diabetics (P < 0.001). In diabetics compared with non-diabetics,
      cardiovascular diseases and cachexia were nearly twice and infections other than
      peritonitis more than three times as frequent in causing death. In diabetics,
      survival was significantly worse (P < 0.0001) and the relative risk of death 2.13
      times higher (P < 0.001). The technique survival and the relative risk of drop
      out were not significantly different in the two groups. Clinical problems were
      the most important cause of drop-out among diabetics. The probability and
      relative risk of drop-out due to peritonitis, as well as of the first peritonitis
      episode, were not significantly different between the two groups and between
      diabetics using or not using intraperitoneal insulin. Days per patient year of
      hospitalization, excluding the first, were 18.4 in diabetics and 14.3 in non
      diabetics. CAPD-related problems caused hospitalization in a similar way in the
      two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7816259
TI  - Computed tomographic peritoneography: CT manifestations in the investigation of
      leaks and abnormal collections in patients on CAPD.
AB  - Continuous ambulatory peritoneal dialysis (CAPD) is now a common form of
      treatment for patients with chronic renal failure. However, peritoneal leaks and
      abnormal intraperitoneal collections can be problematic in these patients,
      leading to poor dialysate returns, anterior abdominal wall oedema, and genital
      oedema. We report on a series of 62 computed tomographic peritoneograms performed
      using a standard protocol on 39 symptomatic patients over 6 years. Thirty-seven
      scans identified peritoneal leaks or abnormal collections, including leaks from
      the present dialysis catheter site and previous catheter sites, and collections
      in inguinal and abdominal herniae. Three patients had abnormalities at two sites
      each. Localization of leaks and collections is of direct use when surgical
      management of these patients is contemplated and this paper aims to illustrate
      the typical CT findings occurring in these patients.

PMID- 7816260
TI  - Pituitary-testicular function in cyclosporin-treated renal transplant patients.
AB  - The aim of this study was to investigate the differences in LH, FSH, PRL and
      testosterone levels in 20 men on haemodialysis and 26 men following renal
      transplantation. Nineteen of the renal transplant recipients were receiving
      cyclosporin, azathioprine, and prednisone, while the seven remaining individuals
      received azathioprine and prednisone. A subgroup of eight patients were also
      studied longitudinally while undergoing maintenance haemodialysis and after
      transplantation. The results show that successful renal transplantation resulted
      in a normalization of hormone levels in either the cross-sectional or
      longitudinal groups, the degree of which was unaffected by treatment modality.
      Cyclosporin given in therapeutic doses does not alter the pituitary-testicular
      function in renal transplant recipients.

PMID- 7816261
TI  - Renal effects of maintenance low-dose cyclosporin A treatment in psoriasis.
AB  - The renal effects of low-dose cyclosporin A (CsA) treatment in severe psoriasis
      was investigated in 10 patients treated with a mean CsA dose of 3.23 (range 1.94
      4.10) mg/kg/day for 12 months. The psoriasis area and severity index was reduced
      by 63-76%. Ambulatory GFR (iothalamate-125I), ERPF (hippuran-131I), RVR and MAP
      were examined at 3-months intervals. A control renal biopsy was performed shortly
      before treatment start and a second biopsy was taken after 12 months of therapy.
      GFR was slightly but significantly reduced after 6 and 9 months; after 12 months
      the decrease was not significant (121.0 +/- 7.6 versus 115.2 +/- 7.8
      ml/min/1.73M2, P > 0.10). After 12 months serum creatinine increased from 82 +/-
      4 to 94 +/- 7 mumol/litre (P < 0.05), while an insignificant increase of ERPF was
      seen and FF decreased from 0.29 +/- 0.01 to 0.26 +/- 0.01 (P < 0.05). MAP
      remained unchanged. GFR and serum creatinine correlated significantly within each
      3-month interval. A slight de novo interstitial fibrosis was seen in the second
      biopsy in 4 of 10 patients receiving a mean CsA dose of 3.2-4.1 mg/kg/day. In
      three of these patients a concomitant rise in serum creatinine was seen. In
      conclusion, low-dose CsA was associated with reversible fall in GFR and
      potentially progressive structural changes not always accompanied by
      corresponding functional alterations. One should consider reducing the daily dose
      of CsA to 3.0 mg/kg bodyweight or less in CsA therapy up to 1 year.

PMID- 7816263
TI  - In-vitro steroid sensitivity in patients with chronic uraemia and renal
      transplantation: possible association with HLA phenotypes.
AB  - We studied in-vitro steroid sensitivity using the test of ADCC in 207
      haemodialysed chronic uremic patients, 85 renal transplant patients, and 75
      healthy blood donors as normal controls. The association of HLA phenotypes with
      the in-vitro steroid sensitivity was assessed. The proportion of steroid
      sensitive subjects was significantly higher in the normal control group than in
      the patients. A significant association was observed between HLA B8 carriers and
      steroid resistance and between HLA DR6 carriers and steroid sensitivity.

PMID- 7816262
TI  - Effect of donor source on renal allograft function in children on triple
      immunosuppression.
AB  - Results of renal transplantation using cadaver donors (CAD) are usually inferior
      to those using living related donors (LRD). We have previously reported 100% 1
      year CAD and LRD graft survival using adult cadaver donors and triple
      immunosuppression. In the present study glomerular and tubular function of 23 LRD
      and 22 CAD grafts (median ages 3.5 and 2.6 years) were compared during 3 years
      after transplantation. Glomerular filtration rate (GFR) and renal plasma flow
      were lower in CAD grafts but remained stable in both groups. The mean GFRs were
      87.3 and 63.2 ml/min/1.73 m2 at discharge and 82.8 and 72.5 ml/min/1.73 m2 at 36
      months in LRD and CAD grafts respectively. No significant differences were found
      after 6 months. Tubular function was good in both groups. The only significant
      difference was in urate handling at 36 months (mean serum urate 396 mumol/l in
      CAD, 301 in LRD grafts, P < 0.05). Cyclosporin nephrotoxicity manifested as
      hyperkalaemia due to reduced distal potassium secretion and/or adrenal
      suppression. In conclusion, donor source had little effect on the development of
      progressive allograft dysfunction using adult CAD grafts and triple
      immunosuppression with CsA administered in three daily doses to preschool
      children.

PMID- 7816264
TI  - Renal disease in POEMS syndrome: report on a case and review of the literature.
AB  - POEMS syndrome is a multisystem disorder associated with plasma cell dyscrasias.
      This report describes a patient with POEMS-associated renal disease and reviews
      the literature on biopsy-proven renal involvement in POEMS syndrome. Our patient
      had glomerulonephritis with membranoproliferative features on light-microscopy
      without characteristic findings on immunofluorescence, and with ultrastructural
      evidence of glomerular microangiopathy. Ultrastructural evidence of
      microangiopathy was also found in vasa nervorum. In 20 other cases of POEMS
      associated renal disease, 16 had glomerular disease. Light-microscopy showed
      membranoproliferative-like glomerulopathy in 14 patients and glomerular
      microangiopathy in two. Ultrastructural evidence of microangiopathy was present
      in all 15 patients in whom electron-microscopy was done. Thus, in most patients
      with POEMS-associated glomerular disease a characteristic lesion is present with
      evidence of endothelial injury. As endothelial damage is also found in endoneural
      vessels, generalized endothelial injury may play a role in non-renal
      manifestations of POEMS syndrome. In previous reviews manifestations of the POEMS
      syndrome were similar for patients with or without myeloma. Among patients with
      biopsy-proven glomerular disease, however, myeloma patients are underrepresented.
      Whether this represents a sampling error or has true pathophysiological
      significance remains to be established.

PMID- 7816265
TI  - Renal thrombotic microangiopathy mimicking active SLE nephritis.

PMID- 7816266
TI  - A case of Takayasu's arteritis, nephrotic syndrome, and systemic amyloidosis.

PMID- 7816267
TI  - Malignant hypertension and renal failure: scleroderma renal crisis or renal
      artery stenosis?

PMID- 7816268
TI  - Ketoconazole in the treatment of recurrent nephrolithiasis associated with
      sarcoidosis.

PMID- 7816269
TI  - True aneurysm of the transplanted renal artery in a kidney transplant recipient.

PMID- 7816270
TI  - Streptococcal toxic shock syndrome complicating necrotizing fasciitis in a renal
      transplant patient.

PMID- 7816271
TI  - Spurious elevation of serum thyrotropin (TSH) after OKT3 administration.

PMID- 7816272
TI  - Cutaneous and mucosal nodules in a transplanted patient.

PMID- 7816273
TI  - No acceleration and possibly slower progression of renal failure during
      calcitriol treatment in predialysis chronic renal failure.

PMID- 7816274
TI  - Prospective study of HPV DNA in cervical specimens from women with renal
      transplants.

PMID- 7816275
TI  - Renal impairment in hypothyroidism.

PMID- 7816276
TI  - Does ethanol have toxic effects on the kidney?

PMID- 7816277
TI  - Treatment of Wegener's granulomatosis: the view from two non-nephrologists.

PMID- 7816278
TI  - Accurate and feasible measurements of GFR--is the iohexol clearance the answer?

PMID- 7816279
TI  - Painless subcutaneous erythropoietin (rHuEpo) injection--is it the panacea?

PMID- 7816280
TI  - Reuse of haemodialysers.

PMID- 7816281
TI  - Intrarenal localization of interleukin-1 beta mRNA in crescentic
      glomerulonephritis.
AB  - Il-1 beta is a potent proinflammatory peptide, and induces expression of other
      cytokines which are involved in the immune response. Kidney biopsies from nine
      patients with crescentic GN were studied by in-situ hybridization to determine
      the site of expression of Il-1 beta mRNA. Biopsies from nine patients with
      nonproliferative renal disease were studied as negative controls, and tonsillar
      tissue was studied as a positive control. An Il-1 beta cDNA probe was 32P
      labelled by random primers and hybridized to paraffin-embedded tissue sections
      after de-waxing. Il-1 beta mRNA was expressed in tonsil, but not in negative
      controls. Positive mRNA expression was seen in four of the nine crescentic
      biopsies. This was observed in interstitial cells with morphological
      characteristics of macrophages adjacent to tubular cells, in cells within the
      glomerular tuft, and in tubular epithelial cells. Il-1 beta mRNA is expressed in
      renal tissue in crescentic GN. Tubular and interstitial expression of Il-1 beta
      mRNA appears of equal prominence to glomerular expression. Intrarenal cytokine
      synthesis may be involved in the pathogenesis of crescentic glomerulonephritis.

PMID- 7816282
TI  - Short-term niflumic-acid-induced acute renal failure in children.
AB  - Several reports emphasize the adverse effects of non-steroidal anti-inflammatory
      drugs (NSAIDs) on renal function. We have observed over the last 10 years seven
      cases of acute renal failure (ARF) due to immune interstitial nephritis in
      children. A recommended oral or rectal dose of niflumic acid was prescribed for
      ear-nose-throat disorders. Length of exposure was 1-5 days. Clinical symptoms
      (oedema, oliguria or anuria) appeared between 3 and 6 days. Three patients had
      previously received the drug. Hypersensitivity signs (fever, skin rash,
      eosinophilia, and/or increased IgE) were present in all cases, leukocyturia in
      five cases, and haematuria in six cases. Renal biopsy showed interstitial lesions
      with lymphocyte, eosinophil, and plasma cell infiltrates without tubular cell
      necrosis. Glomeruli were normal on light-microscopy, except in one patient.
      Electron-microscopy showed extensive podocyte fusion in two patients, who had
      clinical and laboratory evidence of nephrotic syndrome (NS). ARF rapidly
      disappeared after NSAID withdrawal, except in two patients whose renal failure
      was irreversible despite methylprednisolone bolus. ARF is very rare in children
      treated with niflumic acid. When ARF occurs, different pathophysiological
      mechanisms are involved but the most common is immunological.

PMID- 7816283
TI  - Inverse relationship between serum cholinesterase activity and the administration
      of cyclophosphamide: an index of cyclophosphamide therapy.
AB  - To determine whether serum cholinesterase activity can be a monitoring index of
      cyclophosphamide therapy in patients with steroid-resistant glomerulopathy, we
      compared the cholinesterase activity of 37 patients who received a combined
      therapy that included the use of cyclophosphamide, prednisolone, antiplatelet
      drugs, and anticoagulant drugs, with the cholinesterase activity of 25 patients
      who received prednisolone therapy that excluded cyclophosphamide from the
      combined therapy. In the prednisolone and the combined groups, cholinesterase
      activity declined as shown in the following formula: Y = 371-26.4 x log(X): (r2 =
      0.28), Y = 444-147.7 x log(X): (r2 = 0.95), respectively. (Y: cholinesterase
      activity, X: the day after treatment). In the combined therapy group, the
      prevalence of adverse reactions following treatment in the subgroup below 200 U/l
      of cholinesterase activity was significantly greater (P < 0.01) than that in the
      subgroup above 200 U/l of cholinesterase activity. However, there was no
      significant difference (P < 0.25) in the prevalence of adverse reactions between
      the subgroups with more or less than 184 U/l of cholinesterase activity following
      treatment. These results suggest the importance of not going below 200 U/l of
      cholinesterase activity after treatment when the normal cholinesterase activity
      range is between 300 and 760 U/l (e.g. less than 65% of the lowest value of the
      normal range of other hospitals) in order to eliminate the hazards of
      cyclophosphamide to the patients with steroid-resistant glomerulopathy.

PMID- 7816285
TI  - Knowledge of renal histology alters patient management in over 40% of cases.
AB  - There is great debate as to whether the benefit gained from the knowledge of
      renal histology outweighs the risk to the patient from the biopsy procedure. We
      conducted a prospective study of 276 native renal biopsies performed on 266
      patients from a single centre in 1991 to assess the effect of the knowledge of
      renal histology on patient management. Biopsies were performed under ultrasound
      guidance using the Trucut biopsy needle. The indications for biopsy were: non
      nephrotic proteinuria alone (25), haematuria and proteinuria (28), nephrotic
      range proteinuria (28), acute renal failure (31), haematuria alone (36), and
      chronic renal failure (128). Two hundred and sixty-three biopsies were
      successful. The mean number of glomeruli obtained was 23, range 0-115. Eight
      patients developed macroscopic haematuria of which two required blood
      transfusion. The result of the biopsy altered management in 24/28 (86%) of cases
      of nephrotic range proteinuria, 22/31 (71%) of cases of acute renal failure,
      58/128 (45%) of cases of chronic renal failure, 9/28 (32%) of cases with
      haematuria and proteinuria, 3/25 (12%) of cases with non-nephrotic proteinuria
      alone, and 1/36 (3%) of cases with haematuria alone. management was altered in
      42% of cases overall. These data suggest that knowledge of renal histology is
      essential in the management of patients with renal disease.

PMID- 7816284
TI  - Kidney damage in long-term lithium patients: a cross-sectional study of patients
      with 15 years or more on lithium.
AB  - The renal risks associated with long-term lithium treatment are a growing
      concern. We have therefore studied renal function by means of glomerular
      filtration rate (GFR) and maximum urinary concentrating capacity (Umax) in 142 of
      215 patients with more than 15 years of lithium treatment in nine psychiatric
      clinics. Data on psychiatric and somatic diseases, hospital admissions,
      cumulative lithium doses, and other psychotropic treatments were extracted from
      the medical records. The patients were investigated according to a standardized
      protocol. GFR was measured as 51Cr EDTA clearance and Umax using the DDAVP test.
      Thirteen patients had had signs of lithium intoxication. GFR was reduced in 21%
      of the patients and Umax in 44%. Nephrogenic diabetes insipidus was present in
      12%. Umax but not GFR was inversely correlated to the cumulative lithium dose.
      Kidney function was more reduced in patients on lithium combined with
      psychotropic treatment and/or concomitant treatment for somatic disorders. Thirst
      was a complaint of 53% of the patients, predominantly those with additional
      psychotropics. We conclude that kidney damage is common in patients on long-term
      lithium treatment and that both glomerular and tubular function are affected.

PMID- 7816286
TI  - Colour-coded Doppler sonography in monitoring native kidney biopsies.
AB  - Two hundred and one patients had biopsies of their native kidneys with ultrasound
      guided needle technique. They were evaluated on the second post-biopsy day with
      colour-coded Doppler sonography. Ten patients out of these 201 were found to have
      an arteriovenous fistula, which remained asymptomatic for the whole follow-up
      period (follow-ups ranged from 2 to 31 months). Four of these 10 patients
      developed a perirenal haematoma as well and five macroscopic haematuria. Our
      study shows that the systematic use of colour-coded Doppler sonography after
      renal biopsy facilitates diagnosis of arteriovenous renal fistula.

PMID- 7816287
TI  - Renal tubular responses to low-dose infusion of angiotensin II in type 1 diabetes
      mellitus; relation to chronic glycaemic control.
AB  - Renal responses to low-dose infusion of angiotensin II (ANGII, 1.25 and 2.5 ng.kg
      1 min-1) were examined in 15 patients with type 1 diabetes and in 10 control
      subjects after pretreatment with lithium carbonate (750 mg, 20 mmol). Mean
      arterial pressure rose during ANGII infusion in both groups. The renal
      haemodynamic response to angiotensin II was not abnormal in the diabetic
      patients. Absolute proximal reabsorption of sodium was increased at baseline in
      the diabetic group, and fell during ANGII. Fractional lithium excretion was
      reduced in the diabetic patients at baseline (P < 0.05), and the fall in
      fractional lithium excretion during ANGII was less than in the control group (P =
      0.012). In the diabetic group correlations existed between glycated haemoglobin
      and baseline glomerular filtration rate (P < 0.05), baseline fractional lithium
      excretion (P = 0.03), and the fall in fractional lithium excretion during
      angiotensin II infusion (P = 0.013). There was no correlation between glycated
      haemoglobin and absolute lithium clearance. Some indices of sodium reabsorption
      by the proximal renal tubule in diabetic patients correlate with prevailing
      chronic glycaemic control, largely reflecting changes in glomerular filtration
      rate. Reduced fractional proximal tubular responsiveness to exogenous angiotensin
      II is consistent with a role for endogenous angiotensin II as one mediator of
      increased tubular reabsorption of sodium in type 1 diabetes, but the data does
      not exclude alternative mechanisms.

PMID- 7816288
TI  - Uraemic toxic retention solutes depress polymorphonuclear response to
      phagocytosis.
AB  - Previous studies from our laboratory have demonstrated that the activity of the
      hexose monophosphate shunt (HMS) pathway in phagocytosis-related respiratory
      burst is disturbed in end-stage renal disease. To determine whether uraemic
      solute retention is responsible for this defect the HMS-path was evaluated by
      measurements of glucose-1-C14 utilization and determination of 14CO2 production
      in polymorphonuclear cells (PMNLs), suspended in normal plasma or uraemic
      biological fluids. Normal PMNLs, while suspended in normal or uraemic plasma,
      were stimulated with either latex, zymosan or Staph. aureus; CO2 generation
      (measured as DPM/10(3) PMNL, normal versus uraemic plasma) was depressed in
      uraemic plasma in response to latex (from 43 +/- 5 to 20 +/- 3), zymosan (from 72
      +/- 8 to 47 +/- 4) (P < 0.01), and Staph aureus (from 73 +/- 17 to 47 +/- 8
      DPM/10(3) PMNL) (P < 0.05). The degree of inhibition was similar for each
      stimulus. To characterize the substances responsible for this defect we
      fractionated uraemic plasma ultrafiltrate by polarity-based semipreparative C18
      reversed phase HPLC and found a decreased response to Staph. aureus in the
      presence of fraction 2 (from 102 +/- 13 to 23 +/- 10 DPM/10(3) PMNL, P < 0.05),
      and in fractions 8 and 11 (lowest value in fraction 8, 54 +/- 14 DPM/10(3) PMNL,
      P < 0.05 versus control). The pattern of HPLC elution on a gradient from 100%
      formiate (pH 4.0) to 100% methanol indicates that there are at least two
      chemically distinguishable groups of compounds, one hydrophilic (in fraction 2),
      and one lipophilic (in fractions 8 and 11). We conclude that uraemic biological
      fluids contain factors that inhibit HMS activity related to phagocytosis, and
      that at least two groups of components with different characteristics are
      involved.

PMID- 7816289
TI  - Influence of ANF on the cardiovascular response to volume expansion in
      haemodialysis patients.
AB  - Plasma ANF concentration in uraemic patients is very sensitive to changes in
      extracellular volume. It is unknown, however, if the release of this vasoactive
      hormone has a compensatory role in the haemodynamic response to extracellular
      volume expansion in these patients. We investigated the effect of isolated
      ultrafiltration followed by isovolumic re-expansion by saline in seven
      haemodialysis patients. The experiment was repeated on two occasions and the UF
      rate as well as the rate of volume re-expansion in the two studies were
      accurately matched. During the phase of volume re-expansion, we infused either
      ANF (0.83 microgram/min) or a placebo, in random order and cross-over. Central
      venous pressure, arterial pressure, haematocrit, and plasma ANF concentration
      were measured in baseline conditions, after ultrafiltration, and 0, 15, and 30
      min after isovolumic re-expansion. In the control experiment (placebo), isolated
      ultrafiltration caused a marked reduction in central venous pressure and in
      arterial pressure and a pronounced haematocrit increase. These changes were
      reversed by volume re-expansion. In the active experiment, during the phase of
      volume re-expansion ANF infusion doubled plasma ANF concentration as compared to
      control experiment but it did not affect the ongoing haemodynamic response nor
      the haematocrit changes. Doubling of plasma ANF concentration has no influence on
      the haemodynamic and microcirculatory adaptations to acute volume expansion in
      haemodialysis patients. The data indicate that it is unlikely that raised plasma
      ANF concentration has a major role in the cardiovascular response to acute
      extracellular volume expansion in these patients.

PMID- 7816290
TI  - Assessment of refill and hypovolaemia by continuous surveillance of blood volume
      and extracellular fluid volume.
AB  - During renal replacement therapy hypovolaemia due to ultrafiltration (UF) may,
      when not sufficiently counteracted by refill from the interstitium, result in
      hypotension. Combining two recently developed methods the haemodynamic process of
      refill was studied in order to find characteristics featuring hypotension.
      Relative blood volume (BV) and extracellular fluid volume (EFV) were measured
      continuously in 40 stable haemodialysis patients by means of an optical and a
      conductivity technique respectively. Regarding their postdialytic (PD) EFV the
      patients were divided into three groups: normohydrated (N, n = 20), dehydrated
      (D, n = 11) and overhydrated (O, n = 9). Significant differences between the
      groups were assessed in BV decrease (after 2 h until the end of treatment P <
      0.05 and after 3 h P < 0.01), EFV decrease (after 3 h P < 0.05) and occurrence of
      hypotensive episodes (N,5; D,7; O,none; P < 0.01). During the entire session the
      speed of BV decrease was significantly higher in hypotensive patients (H) than in
      non-hypotensive patients (non-H). At the moment of hypotension (after 141 +/- 49
      min) residual BV was less (P < 0.0005) in H (87.7 +/- 5.2%) than at the
      corresponding moment in non-H patients (96.5 +/- 4.0%). PD BV and PD EFV, both
      expressed as a percentage of the starting value, correlated significantly (r =
      0.63, p < 0.005) and UF-volume (differences between the groups were not
      significant) correlated to EFV decrease (r = 0.45, P < 0.005). In conclusion, the
      combination of both non-invasive methods elucidates the pathophysiology of UF
      induced hypotension and provides a means of reducing dialysis morbidity. The
      influence of tissue hydration state on these variables has been shown.

PMID- 7816291
TI  - Fluid recruitment from shell tissues of the body during haemodialysis.
AB  - Patients with kidney failure are prone to accumulate fluids within the
      superficial tissues, leading to a puffiness of the face, hands, and feet. After
      dialysis these symptoms disappear. It was the aim of this study to quantify these
      changes. With the help of A-mode ultrasound in 49 patients (20 females, 29 males)
      the tissue thickness in the forehead and tibia was measured during dialysis. In
      the forehead the tissue thickness before dialysis was 4.01 mm (females) and 3.87
      mm in the males, decreasing continuously during dialysis by 13.6% and 12.8%
      respectively (P < 0.001). In the tibia the tissue thickness was 3.87 mm (females)
      and 3.07 mm (males) and decreased by 12.8% and 23.9% respectively. The sex
      difference was significant (P < 0.05). From these values it was calculated that
      45% of fluid withdrawn came from the superficial shell tissues of the body. It
      was concluded that these tissues serve as water stores in the interdialytic
      phase.

PMID- 7816292
TI  - Anticardiolipin antibodies in children on chronic haemodialysis.
AB  - IgG and IgM anticardiolipin antibody (Ab) concentrations were determined in serum
      samples of 48 children with end-stage renal disease (ESRD) on haemodialysis using
      ELISA technique in an attempt to analyse their possible role in the occurrence of
      thrombosis of the vascular access. Ten normal healthy children were studied as a
      control group. The positivity of anticardiolipin Ab isotypes both IgM and IgG was
      high in children with ESRD on haemodialysis. Children with positive
      anticardiolipin Ab had significantly higher incidence of prior thrombosis of
      vascular access. Also, these antibodies should be considered as markers of high
      risk for fistula thrombosis.

PMID- 7816293
TI  - Analysis of the efficacy of measures to reduce pain after subcutaneous
      administration of epoetin alfa.
AB  - Pain at the injection site with subcutaneous administration of epoetin alfa
      preparations is a common adverse event, and sometimes precludes self
      administration. The pain is caused mainly by the vehicle. The present studies
      were designed to assess whether pain after subcutaneous administration of the
      vehicle can be influenced by making the solution iso-osmotic, or by diluting the
      vehicle by the bacteriostatic agent benzyl alcohol saline (BAS). The volumes
      injected were 1 ml. We also determined whether reduction of the injected volume
      of 1 ml to 0.33 ml or to 0.1 ml could be of clinical importance. One millilitre
      of normal saline served as a placebo control. The studies were done in a double
      blind, placebo-controlled, randomized order, cross-over fashion in healthy
      volunteers. Pain scores were obtained from visual analogue pain scales with no
      divisions and from 5-point verbal descriptive pain scales. Dilution of the
      vehicle with BAS resulted in significantly less pain (P < 0.0001) after
      subcutaneous injection, comparable to levels obtained with normal saline. Making
      the vehicle iso-osmotic had no effects. Injection of smaller volumes of the
      vehicle was beneficial with 0.1 ml (P < 0.0001), but the reduction to 0.33 ml was
      not statistically significant.

PMID- 7816294
TI  - Pain after subcutaneous injection of recombinant human erythropoietin: does Emla
      cream help?
AB  - Recombinant human erythropoietin (rHuEpo) is used to correct anaemia in dialysis
      patients. Subcutaneous administration of rHuEpo may be associated with pain at
      the injection site. This study assessed the pain of subcutaneous infiltration of
      two different preparations of rHuEpo, alpha and beta, and the value of a local
      anaesthetic (Emla) cream, in reducing the pain of infiltration. Forty-eight
      haemodialysis patients were enrolled into a double-blind, placebo-controlled,
      paired-comparison study. Pain was assessed using a visual analogue scale, a
      verbal descriptive scale and a direct comparison between paired treatments.
      Subcutaneous injection of rHuEpo alpha was more painful than rHuEpo beta (P <
      0.001); using placebo cream 42% of patients described the pain of rHuEpo alpha as
      severe or very severe, whereas none of the patients found rHuEpo beta so painful.
      Application of Emla for at least 2 h prior to injection resulted in a significant
      reduction in the pain of both preparations, but was unable to reduce the pain of
      rHuEpo alpha to that of rHuEpo beta. Subcutaneous injection of rHuEpo alpha is
      more painful than rHuEpo beta, even after application of Emla. Although the
      discomfort of rHuEpo beta is graded as very mild by most adult patients the use
      of Emla is associated with a significant reduction in discomfort, which may be of
      benefit to paediatric patients.

PMID- 7816295
TI  - Relationship between pruritus, transepidermal water loss, and biochemical markers
      of renal itch in haemodialysis patients.
AB  - The pathogenesis of pruritus in patients undergoing chronic haemodialysis is
      unknown. Dryness of the skin is common in uraemic patients, and a correlation
      between xerosis and pruritus has been reported. Transepidermal water loss (TEWL)
      is a measure of cutaneous barrier function and also reflects skin water content.
      In this study the transepidermal water loss was measured at four sites pre- and
      postdialysis in 20 subjects undergoing chronic haemodialysis and in 16 healthy
      controls. Patients were weighed before and after dialysis and blood was taken for
      measurement of urea, creatinine, calcium, magnesium, phosphate and haemoglobin.
      All patients had parathyroid hormone measured within 3 months of the assessment.
      There was no significant difference in TEWL between patients and controls, with
      control values in general being between pre- and postdialysis rates of TEWL, and
      no correlation between TEWL and the presence or absence of pruritus. There was no
      significant differences between the pruritic and non-pruritic patients for any of
      the biochemical markers measured. Finally there was no significant correlation
      between the percentage water loss and TEWL. These findings indicate that pruritus
      of chronic haemodialysis is not related to abnormalities of cutaneous
      permeability.

PMID- 7816296
TI  - High- and low-flux acetate-free biofiltration: experimental assessment of calcium
      mass balance and intact parathyroid hormone behaviour.
AB  - We studied total calcium mass balance and plasma intact parathyroid hormone
      behaviour in 10 uraemic patients who underwent acetate-free biofiltration carried
      out in accordance with six different dialytic schedules, where either a
      polyacrylonitrile or a polysulphone membrane was used. Schedules 1 and 2 involved
      a reinfusion flow rate of 33.3 ml/min with a dialysate calcium concentration
      (DCa) of 1.75 and 2 mmol/l respectively; in schedule 3, 4, 5 and 6 reinfusion
      flow rate amounted to 50 ml/min and DCa was respectively of 1.75, 2, 2.25 and 2.5
      mmol/l. Dehydration remained unchanged in all schedules: 700 g/h. Finally high-
      and low-flux acetate-free biofiltration are able to induce different Ca mass
      balance which may suit different therapeutic contexts. Ca mass balance was either
      positive or negative depending on reinfusion flow rate and DCa. With a reinfusion
      flow rate of 33.3 ml/min a DCa of at least 2 mmol/l was necessary to obtain a
      positive mass balance, while with a reinfusion flow rate of 50 ml/min DCa had to
      equal 2.25 mmol/l. In high-flux acetate-free biofiltration, the estimation of
      predialytic Ca2+ and DCa values, using a simple formula, allows prediction of the
      mass balance that will be attained. At the end of acetate-free biofiltration,
      intact parathyroid hormone always decreased when a polyacrylonitrile membrane was
      employed while it increased, in the presence of negative Ca mass balance with a
      polysulphone membrane.

PMID- 7816297
TI  - Complement activation is influenced by the membrane material, design of the
      dialyser, sterilizing method, and type of dialysate.
AB  - The complement system becomes activated during blood-membrane contact in the
      dialyser. This study was designed to evaluate to what extent the dialyser design,
      the sterilization method, and the type of dialysate influence complement as
      measured by C3d. Twelve patients were dialysed three times on each of four
      different dialysers. Two hollow-fibre dialysers made of cuprophane (Hf-CuE
      ethylene-oxide-sterilized, Hf-CuS steam-sterilized) were compared with two plate
      dialysers made of cuprophane (P-Cu) or polycarbonate (P-Pc). Five patients were
      dialysed with acetate and seven with bicarbonate. Differences in C3d between at
      start of dialysis and after 180 min were calculated. C3d was increased more by P
      Cu than by the other dialysers (P < 0.012, n = 12). In the bicarbonate group, C3d
      was increased more by P-Cu than by Hf-CuS or P-Pc (P < 0.022, n = 7) and more by
      Hf-CuE than Hf-CuS (P = 0.013). In the acetate group, C3d was increased more by
      Hf-CuS and P-Cu than by P-Pc (P < 0.006, n = 5). In conclusion, complement
      activation during dialysis varied due to membrane material, membrane design,
      sterilization method, and dialysate composition.

PMID- 7816298
TI  - Development of cytotoxic antibodies following renal allograft transplantation is
      associated with reduced graft survival due to chronic vascular rejection.
AB  - We prospectively followed 64 patients who had had no cytotoxic antibodies prior
      to first cadaveric renal allograft transplantation for post-transplant
      antibodies. During a mean follow-up period of 62 months (range 45-92) cytotoxic
      antibodies developed in 36 patients (56%). Sixteen grafts were lost due to
      chronic vascular rejection in the group of patients who developed antibodies
      compared to two in those who remained antibody negative, P < 0.01. Renal function
      was worse in the antibody-positive group, median serum creatinine 215 mumol/l
      (131-256) (interquartile range) versus 111 mumol/l (98-127) in the antibody
      negative group, P = 0.002, and creatinine clearance 39 ml/min (25-55) versus 90
      ml/min (55-104), P < 0.001. There were no significant differences in
      immunosuppressive protocol, HLA-mismatching, blood transfusion history, the
      number of acute rejection episodes, mean arterial blood pressure, or proteinuria
      between the groups. The presence of cytotoxic antibodies predated the classical
      manifestations of chronic vascular rejection. This suggests that humoral
      mechanisms may play a role in the development of chronic vascular rejection.

PMID- 7816299
TI  - Outcome of renal transplantation in hepatitis BsAg-positive patients.
AB  - Renal transplantation of patients with previous or ongoing hepatitis B virus
      infection has been tempered with a concern that immunosuppression may lead to
      viral replication and progressive liver damage. However, renal transplantation as
      therapy for end-stage renal failure in these patients improves quality of life
      and reduces the risk of body fluid exposure to their carers. To assess the long
      term outcome of renal transplantation in hepatitis-BsAg-positive patients a
      retrospective study was carried out on the patients transplanted in this unit
      since 1969. Seventy-six patients received 98 grafts up to December 1991; follow
      up was available on 68. Thirty-one of the 68 patients died; the causes of death
      were infective 23, cardiovascular 6, liver failure 4, pancreatitis 2, aspiration
      1, GI haemorrhage 1, and stopped therapy 1. Serological markers of hepatitis B
      virus infection did not correlate with outcome. The risk of developing liver
      failure after renal transplantation appears small in the hepatitis-BsAg-positive
      patients and no patient should be denied a renal transplant on the basis of
      serological tests.

PMID- 7816300
TI  - Immunological studies of IgA nephropathy in blacks reveal elevations of serum
      IgA2 as well as IgA1.
AB  - Although IgA nephropathy (IgAN) is recognized worldwide as the most common
      primary glomerulonephritis, the prevalence of this disease among American blacks
      is strikingly low despite the frequency of other renal disorders. We have
      previously described the clinical features of 27 black patients enrolled in a
      multicentre IgAN database; in this paper we report several immunological
      parameters of the disease in this population. Quantification of serum
      immunoglobulins revealed significantly higher concentrations of total IgA, IgA1
      and IgA2 (P = 0.0001, 0.002 and 0.005 respectively) in the patients, but no
      significant increases in IgG or IgM. Examination of immunoglobulin synthesis by
      peripheral blood lymphocytes indicated relatively few differences in the
      secretion of immunoglobulins by patients compared to healthy American blacks. The
      spontaneous production of total IgA, IgA1, and IgA2 in patients was depressed
      compared to the control subjects (P = 0.02, 0.04, 0.03,), yet the ratio of
      IgA1:IgA2 was normal. Stimulation with pokeweed mitogen enhanced secretion of
      immunoglobulin in both subject groups. However, a significantly greater IgA1:IgA2
      ratio was noted in the patients (P = 0.002). Circulating immune complexes
      containing C3 and IgA as well as C3 and IgM were elevated in the patients (P =
      0.0006, 0.0003 and 0.02, respectively). These immunological aberrancies did not
      correlate with clinical manifestations of disease. These data suggest the immune
      abnormalities of black IgAN patients are similar to, but not identical with,
      those of white patients.

PMID- 7816301
TI  - Circadian rhythm of glomerular filtration rate in patients after kidney
      transplantation.
AB  - Within 6 months of a kidney transplantation the graft can be regarded as an organ
      deprived of its innervation. We analysed whether the transplanted kidney has a
      diurnal rhythm of its glomerular filtration rate (GFR) similar to the GFR rhythm
      that has been demonstrated in normal individuals and in patients with nephrotic
      syndrome. GFR was measured by inulin clearances every 3 h during 1 day of bed
      rest and identical food and fluid intake per 3 h in seven patients, 4-7 months
      after a successful kidney transplantation, and in 10 healthy volunteers. Similar
      to these healthy subjects, a normal circadian rhythm of GFR was detected in all
      but one patient with a maximum of 57 (range 45-82) ml/min in daytime, a minimum
      of 47 (range 36-70) ml/min during the night and a relative amplitude of 21 (range
      10-41)%. The circadian rhythm of GFR was absent in the patient with the lowest
      value of GFR (39 ml/min). In conclusion, GFR has a circadian rhythm in patients
      studied within 6 months of a kidney transplantation, despite the absence of renal
      innervation.

PMID- 7816302
TI  - Rhabdomyolysis and renal failure after intra-arterial temazepam injection.

PMID- 7816303
TI  - Treatment of diphenhydramine intoxication with haemoperfusion.

PMID- 7816304
TI  - Renal amyloidosis without urinary abnormality in a potential live-kidney donor.

PMID- 7816305
TI  - IgA nephropathy: report of a symposium down under.

PMID- 7816306
TI  - The role of Domenico Cotugno in the history of proteinuria.

PMID- 7816307
TI  - The proteinuric lady with a deformed knee.

PMID- 7816308
TI  - Collapsing focal segmental glomerulosclerosis associated with visceral
      leishmaniasis.

PMID- 7816309
TI  - Response to alpha 2B interferon (IFN) treatment in a haemodialysis patient with
      chronic hepatitis C.

PMID- 7816310
TI  - Immunoreactive endothelin in dialysis patients: diabetics versus non-diabetics.

PMID- 7816311
TI  - Effect of cisapride on gastric emptying in haemodialysis patients.

PMID- 7816312
TI  - Aluminium overload influences cognitive function in patients on dialysis.

PMID- 7816313
TI  - ACE inhibitors do not affect erythropoietin efficacy in haemodialysis patients.

PMID- 7816314
TI  - Ultrastructure of Merkel-like cells labeled with carbocyanine dye in the non
      taste lingual epithelium of the axolotl.
AB  - Fluorescent carbocyanine dye (diI), applied to the glossopharyngeal (IX) nerve of
      the axolotl, transneuronally labeled solitary cells in the non-taste lingual
      epithelium. With diaminobenzidine (DAB), the diI was photoconverted to a dark,
      electron-dense product. The labeled cell had a large nucleus with invaginations,
      dense-cored vesicles in the cytoplasm, and finger-like processes. These are
      reminiscent of morphological features of cutaneous Merkel cells, suggesting that
      solitary cells innervated by the IX nerve are associated with mechanosensory
      function of the IX nerve system.

PMID- 7816315
TI  - Acute stress stimulates secretion of GHRH and somatostatin into hypophysial
      portal blood of conscious sheep.
AB  - The effects of acute stress on growth hormone (GH) secretion and the mechanisms
      involved in its changes have been investigated in sheep. An acute isolation
      restraint stress induced a rapid and significant increase in jugular GH levels in
      12 out of 14 rams. GH-releasing hormone (GHRH) and somatostatin secretion during
      the same stress were studied in 5 animals prepared for hypophysial portal blood
      collection. A 3.5-fold increase in portal GHRH levels was observed concomitantly
      with a slight elevation in portal somatostatin. Portal corticotropin-releasing
      hormone (CRH) and jugular cortisol plasma levels increased during the same
      stress. Our data suggest that an isolation-restraint stress stimulates GH
      secretion in the sheep and that GHRH may be responsible for GH response.

PMID- 7816316
TI  - Effects of neutron-gamma irradiation on striatal D1 and D2 receptor distribution.
AB  - The early effects of neutron irradiation on the striatal D1 and D2 dopaminergic
      receptor distribution were investigated by quantitative receptor autoradiography.
      One hour after exposure at the dose of 8.4 Gy, an increase of D1 (+21%) and D2
      (+25%) receptor density was observed in the striatum, located at the most
      anterior levels, containing the richest plexus of dopaminergic fibers afferent
      from the substantia nigra. Regional differences in changes of D1 and D2 receptor
      density were observed. This up-regulation could contribute to the development of
      early radio-induced neuro-vegetative syndrome.

PMID- 7816317
TI  - Ketamine prevents ECS-induced synaptic enhancement in rat hippocampus.
AB  - Electrical induction of seizure activity profoundly impairs hippocampal long-term
      potentiation (LTP) in rats. A similar effect may account for the memory
      dysfunction observed after electroconvulsive stimulation in humans and other
      species. The co-administration of ketamine with the induction of
      electroconvulsive seizures (ECS) was evaluated as a possible method for reducing
      the impact of ECS on hippocampal synaptic plasticity in rats.
      Electrophysiological studies in vivo showed that both the enhancement of the EPSP
      slope and the subsequent reduction of experimentally induced LTP in the dentate
      gyrus by repeated, spaced ECS were significantly attenuated by ketamine
      anaesthesia. The findings suggest that ketamine may protect against ECS-induced
      memory impairment and thus prove useful in reducing the transient cognitive
      impairment following electroconvulsive therapy (ECT).

PMID- 7816318
TI  - Lactate efflux and intracellular pH during severe hypoxia in rat cerebral cortex
      in vitro studied by nuclear magnetic resonance spectroscopy.
AB  - Intracellular pH (pHi) and lactate were monitored in a superfused brain slice
      preparation using NMR spectroscopy in order to study the role of lactate washout
      in maintenance of pHi during hypoxia. Data are consistence with a functioning
      lactate-H+ cotransport in the energetically intact cerebral cortex. This pathway
      is not, however, linked to regulation of pHi during energy failure with external
      pH of 6.8 and thus appears not to have physiological impact in H+ homeostasis
      during cerebral hypoxia.

PMID- 7816319
TI  - Morphometric analysis of cisplatin-induced neurite outgrowth in N1E-115
      neuroblastoma cells.
AB  - Cisplatin, a widely used cytostatic drug for the control of a variety of
      neoplastic tumors, unexpectedly induced neurite outgrowth in N1E-115
      neuroblastoma cells and this phenomenon was studied further in detail with
      morphometric analysis. As expected, cisplatin dose-dependently reduced cell
      number. At the same time, however, cisplatin affected the morphology of the
      neuroblastoma cells that changed from small rounded cell bodies into large flat
      cell bodies with neurites. The neurite length/cell as a function of cisplatin
      concentration showed a bell-shaped curve. The maximal effect (1200% of control)
      on neurite length/cell was observed at 1 microgram/ml cisplatin. In conclusion,
      cisplatin induced cellular differentiation in N1E-115 neuroblastoma cells at and
      just above threshold doses for cytostatic activity.

PMID- 7816320
TI  - Induction of Fos-like immunoreactivity in rat oxytocin neurons following insulin
      injections.
AB  - Double immunostaining for oxytocin (OT) and Fos was used to study the
      oxytocinergic system of the rat hypothalamic paraventricular nucleus (PVN)
      following intraperitoneal insulin injections. The expression of c-fos in the PVN
      appeared about 3 h after insulin treatment and was very high after 5 h while no
      labelling was observed in isotonic saline-injected animals. Twelve to 18% of OT
      neurons expressed Fos-like immunoreactivity and these activated neurons were
      found in both the magno- and the parvocellular compartments of the PVN suggesting
      that the OT neuron responses to insulin induced disturbances are complex and
      involve hormonal as well as autonomic pathways.

PMID- 7816321
TI  - Characteristics and localization of high-affinity kainate sites in slide-mounted
      sections of rat cerebellum.
AB  - The characteristics and localization of high-affinity, kainic acid (KA)-sensitive
      glutamate sites have been investigated using a radioreceptor procedure to provide
      insights into specific high-affinity KA receptors identified in molecular
      biological studies. Binding sites identified by employing [3H]KA. in the presence
      of the AMPA-selective antagonist NBQX (1 microM), and slide-mounted, coronal
      sections of rat cerebellum were of high-affinity (Kd 6 nM) and possessed an
      unique pharmacological profile. Specific binding was to a single population of
      sites and fully inhibited by kainoids and glutamate, but essentially insensitive
      to AMPA and willardiines. Autoradiography revealed that the high-affinity KA
      sites were localized to the granule cell layer of cerebellum. The KA site
      resembled both the KA receptor found on spinal motoneurones and the KA-2 type of
      receptor.

PMID- 7816322
TI  - Calbindin D-28k immunoreactivity in the rat cerebellar cortex: age-related
      changes.
AB  - The present study was designed to analyze age-dependent changes in the expression
      of calbindin D-28k immunoreactivity in the cerebellar cortex of male Wistar rats
      aged 3 months (young), 12 months (adult) and 24 months (old). Calbindin D-28k
      immunoreactivity was localized primarily in the cytoplasm of Purkinje neurons and
      in the basal portion of their dendritic processes entering in the molecular
      layer. The expression of calbindin D-28k immunoreactivity was highest in Purkinje
      neurons of adult rats and lowest in Purkinje neurons of old rats. Moreover, the
      number of Purkinje neurons displaying calbindin D-28k immunoreactivity was
      decreased in aged rats. These results demonstrate the occurrence of age-related
      changes in the expression of immunoreactivity of the Ca2+ binding protein
      calbindin D-28k in the rat cerebellar cortex. The possibility that impairment in
      the expression of Ca2+ binding proteins may be involved in changes of
      intracellular Ca2+ homeostasis reported in aging and in some neuro-degenerative
      disorders is discussed.

PMID- 7816324
TI  - The time course of sensory adaptation in the cockroach tactile spine.
AB  - Power-law dynamics have been widely used to fit the adaptation of sensory
      receptors, including the cockroach tactile spine. We used a new log-binning
      technique to re-examine step responses in the tactile spine. The power-law only
      fitted responses over a restricted time period, while a sum of three exponential
      decays gave an accurate fit over the entire response duration.

PMID- 7816323
TI  - Chemically-diverse ligands at the glycine B site coupled to N-methyl-D-aspartate
      (NMDA) receptors selectively block the late phase of formalin-induced pain in
      mice.
AB  - The glycine B receptor partial agonists L 687,414, D-cycloserine and (+)-HA 966,
      and the glycine B receptor antagonists MDL 29,951 and 5,7-dichloro-2,4 dihydroxy
      3-phenyl-quinoline dione (DCPQ) dose-dependently inhibited the late phase (LP) of
      formalin-induced licking (FIL) elicited by intraplantar formalin in mice at doses
      exerting little motor disruption in the rotarod test. In distinction, the early
      phase (EP) of FIL and the writhing response to intra-abdominal acetic acid were
      little influenced and, irrespective of stimulus intensity, they failed to modify
      the tail-flick response to phasic, thermal or mechanical stimulation of the tail.
      In contrast to glycine B ligands, competitive antagonists at the NMDA receptor
      recognition site (CPP, CGS 19755, CGP 34879 and 39551) and blockers of the
      associated ion channel ((+)-MK 801, (-)-MK 801, memantine and ketamine) all
      blocked both the LP and EP of FIL and induced ataxia at comparable doses. In
      conclusion, normalization of transmission at NMDA receptors by inhibition of the
      coupled glycine B site preferentially elicits antinociception against prolonged
      (chemical) noxious stimulation in the absence of a marked influence upon motor
      coordination.

PMID- 7816325
TI  - Responses of neurones in the nucleus paragigantocellularis lateralis to somatic
      nerve stimulation.
AB  - Among the seventy-eight extracellularly recorded neurones in the nucleus
      paragigantocellularis lateralis (PGL), 30 and 31 of them were excited by the
      stimulation of superficial (SPN) and deep (DPN) peroneal nerve, respectively. In
      the other 17 neurones, convergent inputs from both nerves to a single neurone
      were found, and a post-excitatory inhibition was also observed. The consequence
      of the integrated responses to the stimulation of both nerves depended on the
      time interval of the stimuli to them. Excitatory post-synaptic potentials (EPSP)
      were recorded in neurones excited by the stimulation of both nerves. In
      conclusion, the stimulation of SPN and DPN can excite neurones in PGL, at least
      partially, via EPSP through their respective pathways; the integrated responses
      of PGL neurones to both nerves are related to the arrival time of impulses from
      them.

PMID- 7816326
TI  - Electrophysiological correlates of human visual recognition memory.
AB  - In a visual recognition task for random patterns, event-related potentials (ERPs)
      were recorded concurrently with the behavioral performance. A prove stimulus, the
      feature of which was physically different from a sample stimuli to be memorized,
      elicited a posterior negative wave in the 220-280-ms latency range. Stimulus
      complexity and longer retention interval decreased not only the accuracy of
      behavioral performance but also the amplitude of the negative wave. Furthermore,
      when the subject failed to recognize the difference, the negative wave was not
      observed. The posterior negative wave might, therefore, reflect traces of visual
      short-term memory.

PMID- 7816327
TI  - The use of gadolinium to investigate the relationship between Ca2+ influx and
      glutamate release in rat cerebrocortical synaptosomes.
AB  - Gadolinium chloride is a potent blocker of voltage-sensitive Ca2+ channels. When
      added to fura-2 loaded rat cortical synaptosomes 1 min before depolarization with
      33 mM KCl, it causes a dose-dependent inhibition of the resulting rise in
      intrasynaptosomal free Ca2+ with an IC50 of approximately 10 microM. The effect
      of GdCl3 on intrasynaptosomal free Ca2+ is not accompanied by an equivalent
      effect on Ca(2+)-dependent glutamate release. In the presence of 100 microM
      GdCl3, 33 mM KCl does not produce a detectable change in the fura-2 signal but
      Ca(2+)-dependent glutamate release is only reduced by around 12%. Using BaCl2,
      which is less effectively buffered in synaptosomes than Ca2+, we have shown that
      there is residual KCl-stimulated divalent cation entry into synaptosomes in the
      presence of 100 microM GdCl3. These data, combined with those from other
      laboratories, strengthen the argument for localized Ca2+ entry through Ca2+
      channels linked to neurotransmitter release from synaptosomes and add to the
      evidence that the channels may exhibit considerable neurotransmitter specificity.

PMID- 7816328
TI  - Intracisternal injection of pancreatic polypeptide stimulates gastric emptying in
      rats.
AB  - In the present study, we evaluated the effects of central administration of
      pancreatic polypeptide (PP) on gastric emptying of a liquid meal in conscious
      rats using a phenol red method. Intracisternal injection of PP (0.5-2.0
      micrograms) speeds gastric emptying of a test meal in a dose-dependent manner. In
      contrast, i.p. injection of PP at the same doses inhibited gastric emptying in a
      dose-related fashion. Bilateral gastric branch vagotomy abolished the increase in
      gastric emptying evoked by intracisternal PP. These results demonstrate that PP
      speeds gastric emptying through the vagal system when given centrally but slows
      emptying when given peripherally.

PMID- 7816329
TI  - Dextromethorphan attenuates hypoxia-induced neuronal dysfunction in rat
      neocortical slices.
AB  - We investigated the effects of the antitussive dextromethorphan (DM; 100 microM)
      on the extracellular DC potential, extracellular calcium concentration ([Ca2+]o)
      and on stimulus-evoked field potential (FP) responses in rat neocortical slices
      during hypoxia. DM significantly reduced the amplitude of the anoxic
      depolarization (AD) and the associated [Ca2+]o decrease by 47.6% and 48.5%,
      respectively, but did not change the onset latency and the duration of the AD. DM
      did not affect the preservation or recovery of excitatory synaptic transmission
      and significantly suppressed paired-pulse inhibition in the postanoxic recovery
      phase. These results indicate that DM exerts its potential neuroprotective action
      by reducing the hypoxia-induced depolarization and Ca2+ influx.

PMID- 7816330
TI  - Marked increase in histamine H3 receptors in the striatum and substantia nigra
      after 6-hydroxydopamine-induced denervation of dopaminergic neurons: an
      autoradiographic study.
AB  - The bindings of [3H](R) alpha-methylhistamine to histamine H3 receptors were
      investigated in rat brain following intranigral treatment with 6-hydroxydopamine
      (6-OHDA) by quantitative receptor autoradiography. The levels of [3H](R) alpha
      methylhistamine binding sites in the denervated striatum (dorsomedial and
      dorsolateral) and substantia nigra were significantly higher than those in the
      contralateral side 21 days after nigral lesions. Saturation kinetic analysis
      revealed that the maximum binding capacities were up-regulated to about 1.7- and
      1.2-fold those in the contralateral substantia nigra and striatum, respectively.
      These results strongly suggest that H3 receptors in the striatum and substantia
      nigra are influenced by tonic dopaminergic inputs.

PMID- 7816331
TI  - Normal sequences of muscarinic acetylcholine receptors (m1 and m2) in patients
      with Alzheimer's disease and vascular dementia.
AB  - The genes for muscarinic acetylcholine receptors, m1 and m2, were studied in
      autopsied brains from nine Alzheimer's disease, six vascular dementia and three
      control. The genes were amplified by the polymerase chain reaction and sequenced
      by the dideoxy method. Although one DNA polymorphism was found in m1, the deduced
      amino acid sequences of the muscarinic acetylcholine receptor were unchanged. The
      amino acid sequences of m1 and m2 in Alzheimer's disease and vascular dementia
      were intact.

PMID- 7816332
TI  - Enhanced in vitro survival and growth of foetal human mesencephalic dopaminergic
      neurones on laminin and collagen: implications for cell banking.
AB  - Culture of second trimester mesencephalic cells on laminin and collagen substrata
      has been investigated in an attempt to ascertain the effects of these
      extracellular matrix components on survival and growth of central dopaminergic
      (DA) neurones. There were 156.8-186.4% more cells attached to laminin and
      collagen than poly-D-lysine 6 h post-plating. By 24 h there was statistically no
      significant difference in the total number of cells attached to the three
      substrate but in terms of cell type-specific survival the proportion of
      mesencephalic DA neurones surviving on laminin and collagen substrata after 7
      days in culture increased significantly compared with poly-D-lysine (1.4-1.6%
      versus 0.4% of the total cellular population), an effect augmented by bFGF
      treatment, which led to levels of 2% or more, with a concomitant decrease in the
      proportion of attritic DA neurones. These results indicate a critical requirement
      for ECM proteins in the survival and growth of in vitro-propagated central DA
      neurones at the time of plating and throughout the culture period. They also
      imply survival-enhancing interactions of ECM proteins and neurotrophic factors in
      developmental neuronal regulation and provide paradigms for obtaining high yields
      of these cells for neural transplantation cell banks.

PMID- 7816333
TI  - Acute phase-shifting effects of melatonin associated with suppression of core
      body temperature in humans.
AB  - Appropriately administered melatonin is able to phase shift circadian rhythms, to
      induce transient sleepiness and to suppress core body temperature. The
      relationships between these phenomena have not been fully explored. In a double
      blind, placebo-controlled crossover study, 8 healthy males maintained a regular
      sleep-wake cycle in a natural environment throughout. From dusk until 2400 h on
      days (D) 1-4 subjects were in dim artificial lighting (< 100 lux) with darkness
      (< 1 lux) from 2400-0800 h. Sunglasses were worn during the day when outside. At
      1700 h on D3 either melatonin (5 mg) or placebo was administered. Saliva samples
      were collected at 30 min intervals, 1600-2400 h on D3 and D4, and subjective
      alertness rated at 30 min intervals from 1600-2400 h on D3 and hourly from 0800
      2400 h D4. Sleep quality was rated on nights 2, 3 and 4 and core temperature was
      recorded throughout. Melatonin induced a significant suppression of temperature
      and alertness peaking 2.5 h after the dose, together with improved sleep quality
      on the night of D3 and a phase advance of the endogenous melatonin rhythm on D4.
      The degree of phase shift was related to the amount of temperature suppression in
      6 of 7 subjects with detectable melatonin, suggesting that temperature
      suppression is an integral part of the phase-shifting mechanism.

PMID- 7816335
TI  - Differential regulation of c-JUN expression in rat retinal ganglion cells after
      proximal and distal optic nerve transection.
AB  - In adult rats, the distance between the site of axotomy and the cell body
      influences the ability of retinal ganglion cells (RGCs) to survive and regenerate
      an axon. Optic nerves of adult rats were transected 2 mm or 6 mm from the optic
      bulb and RGCs labeled with the fluorescent marker fluorogold. The time course of
      c-JUN expression was monitored immunocytochemically between 3 days and 4 weeks
      after axotomy. c-JUN expression began later and declined faster after distal
      axotomy than after proximal transection of the optic nerve. However, at the same
      time significantly more RGCs survived after distal than after proximal axotomy 3
      and 4 weeks after axotomy. These findings suggest that survival and expression of
      c-JUN in rat RGCs are independently regulated by the length of the optic nerve
      stump after lesion.

PMID- 7816334
TI  - Nitrergic stimulation does not inhibit carbachol-induced inositol phosphate
      generation in the rat anococcygeus.
AB  - Carbachol (50 microM) produced a rapid, transient increase in inositol-1,4,5
      trisphosphate (IP3) levels in the rat anococcygeus; the peak increase observed at
      10 s (3-fold above controls) was greatly reduced in the presence of atropine (100
      nM), but was unaffected by nitrergic stimulation (10 Hz), sodium nitroprusside
      (10 microM) or 8-Br-cyclic GMP (200 microM). Following loading of muscles with
      [3H]myo-inositol, subsequent exposure to carbachol for 30 min resulted in a 6
      fold increase in the accumulation of [3H]inositol-1-monophosphate; again, this
      action of carbachol was greatly attenuated by atropine, but unaffected by
      nitrergic stimulation, sodium nitroprusside or 8-Br-cyclic GMP. It is concluded
      that inhibition of agonist-induced generation of inositol phosphates cannot
      explain the ability of nitrergic activation to relax (by 54-62%) carbachol
      induced tone in this tissue.

PMID- 7816336
TI  - I.c.v. infusions of ACPD(1S,3R) attenuate learning in a Morris water maze
      paradigm.
AB  - The functional role of metabotropic glutamate receptors is beginning to be
      understood. Cognitive effects of metabotropic receptor activation were examined
      in the present study in a Morris water maze following intraventricular (i.c.v.)
      infusions of ACPD(1S,3R). I.c.v. infusions of ACPD substantially increased the
      amount of time animals took to find a hidden platform in a water maze. Current
      results demonstrate that subtoxic doses of ACPD can produce in vivo effects with
      functional significance. Spatial learning abilities are impaired following
      activation of metabotropic receptors with ACPD(1S,3R). Negative implications are
      provided for the use of cognitive enhancing compounds that stimulate metabotropic
      glutamate receptors.

PMID- 7816337
TI  - Glutamate shifts the phase of the circadian neuronal firing rhythm in the rat
      suprachiasmatic nucleus in vitro.
AB  - The effect of glutamate (GLU) on the phase of the circadian neuronal firing
      rhythm of the rat suprachiasmatic nucleus (SCN) was examined in vitro. GLU
      application in late subjective night produces phase-advances whereas GLU applied
      in early subjective night produces either phase-delays or a bimodal peak in the
      firing rhythm that appears to be a combination of phase-advances and phase
      delays. Optic chiasm (OC) stimulation, or exposure of animals to light just prior
      to sacrifice, produces phase-delays in early subjective night, and phase-advances
      in late subjective night. None of GLU, light and OC stimulation produces
      significant phase-changes during subjective day. The results indicate that GLU is
      the neurotransmitter of the retinohypothalamic tract.

PMID- 7816338
TI  - Different modifications of the dopamine metabolism in the core and shell parts of
      the nucleus accumbens following CCK-A receptor stimulation in the shell region.
AB  - After the injection of CCK8 into the posterior N. Acc. of rats DA, DOPAC HVA
      contents were determined from punches of the anterior and posterior N. Acc. and
      VTA. CCK8 (20 pmol/side) modified these levels only in the posterior N. Acc. and
      these responses were inhibited by the CCK-A antagonist devazepide. Five min after
      treatment, DA, DOPAC and HVA were increased in the N. Acc.shell and 10 min later
      they were decreased in the N. Acc.core. These data suggest that in these regions
      CCK8 could both abolish the influence of DA from the core on the transmission of
      motor information and favor that of DA from the shell on emotional-like
      responses.

PMID- 7816339
TI  - Ontogenetic development of gonadotropin-releasing hormone-like immunoreactive
      neurons in the brain of the chum salmon, Oncorhynchus keta.
AB  - In the chum salmon, gonadotropin-releasing hormone-immunoreactive (GnRH-ir) cells
      were first detected in the olfactory placode of embryos at 16 days after
      fertilization, and then appeared sequentially in the olfactory nerve and the
      distal part of the forebrain by hatching. Four months after hatching, the
      terminal nerve was differentiated along the olfactory nerve, and GnRH-ir fibers
      extended to the hypothalamus and hypophysis. GnRH-ir cells occurred later in the
      preoptic area in about 1-year-old juveniles. These data suggest that GnRH neurons
      originate in the olfactory placode and then migrate into the brain along the
      olfactory nerve.

PMID- 7816341
TI  - beta-Amyloid (A beta) deposition in elderly non-demented patients and patients
      with Alzheimer's disease.
AB  - beta-amyloid (A beta) deposition in the medial temporal lobe (MTL) was studied in
      elderly non-demented (ND) cases and in patients with Alzheimer's disease (AD). In
      AD, A beta deposits were present throughout the MTL although density was less in
      the hippocampus than the adjacent cortical regions. In the ND cases, no A beta
      deposits were recorded in 6 cases and in the remaining 8 cases, A beta deposits
      were confined to the cortical regions adjacent to the hippocampus. The mean
      density of A beta deposits in the cortical regions examined was greater in AD
      than in the ND cases but there was a significant overlap between the two groups.
      The ratio of mature to diffuse A beta deposits was greater in the ND than the AD
      cases. In both patient groups, A beta deposits formed clusters in the cortex and
      many tissues exhibited a regular distribution of clusters along the cortex
      parallel to the pia. The mean dimension of the A beta clusters was greater in AD
      than in the ND cases. Hence, few aspects of A beta deposition appeared to
      consistently separate AD from ND cases. However, the spread of A beta pathology
      between modular units of the cortex and into regions of the hippocampus could be
      factors in the development of AD.

PMID- 7816340
TI  - Calyculin A blocks bovine chromaffin cell calcium channels independently of
      phosphatase inhibition.
AB  - The specific phosphatase inhibitor, Calyculin-A (CL-A), decreases high-K
      stimulated catecholamine secretion in bovine chromaffin cells. This effect can be
      split into two components: one needs long exposures to the drug to be elicited,
      and is sensitive to the protein kinase-inhibitor K252a; the other is observed
      after short incubations of CL-A, and is insensitive to K252a. Here we report that
      the latter component is due to an external block, by CL-A, of chromaffin cell
      calcium channels in a voltage-dependent, reversible and phosphorylation
      independent manner.

PMID- 7816342
TI  - Evidence for cholinergic neuronal loss in brain in congenital ornithine
      transcarbamylase deficiency.
AB  - Congenital ornithine transcarbamylase (OTC) deficiency in humans is associated
      with seizures and mental retardation. As part of a series of studies to delineate
      the neurochemical features of OTC deficiency, activities of choline
      acetyltransferase (ChAT) and acetylcholinesterase (AChE), respectively, were
      measured in brain regions of the congenitally hyperammonemic sparse-fur (spf)
      mouse, a mutant with an X-linked inherited defect of OTC. ChAT activities were
      reduced by 63% (P < 0.01) in cerebral cortex of spf mice compared with CD-1/Y
      controls. Activities of the GABA nerve terminal marker enzyme, glutamic acid
      decarboxylase, on the other hand, were within normal limits. Using an
      immunohistochemical technique with a monoclonal antibody to ChAT, a significant
      loss of ChAT-positive neurons was observed throughout the cerebral cortex, septal
      area and diagonal band of spf mice. These results suggest that a loss of
      forebrain cholinergic neurons is a feature of congenital OTC deficiency in these
      mutants. Possible pathogenetic mechanisms responsible for the cholinergic
      neuronal loss in congenital OTC deficiency include neurotoxic effects of ammonia
      and accumulation of quinolinic acid.

PMID- 7816343
TI  - Effects of diabetes on the morphine-induced Straub tail reaction in mice.
AB  - The effects of diabetes on the morphine-induced Straub tail reaction were
      examined in mice. The Straub tail reaction induced by s.c. administration of
      morphine was significantly less in diabetic mice than in non-diabetic mice. The
      morphine-induced Straub tail reaction was significantly reduced following
      pretreatment with beta-funaltrexamine, a selective mu-opioid receptor antagonist,
      in both diabetic and non-diabetic mice. Furthermore, the morphine-induced Straub
      tail reaction was also significantly reduced in both diabetic and non-diabetic
      mice following pretreatment with naloxonazine, a selective mu1-opioid receptor
      antagonist. These results suggest that mice with diabetes are hypo-responsive to
      mu1-opioid receptor-mediated Straub tail reaction.

PMID- 7816345
TI  - Afferent contributions to intermediate area of the cat ventral medullary surface
      during mild hypoxia.
AB  - The intermediate area of the cat ventral medullary surface activates to mild
      hypoxia. Carotid body and vagal afferent contributions to this response were
      examined by recording activity levels, measured as changes in scattered 660 nm
      light, from the medullary surface in 7 anesthetized, spontaneously breathing cats
      following 12% O2 in N2 ventilatory challenge. A miniaturized video camera
      collected images synchronous with the peak of cardiac R wave at 1/s, from a 3.2
      mm diameter area, before, and following bilateral carotid sinus denervation (CSD)
      and vagotomy. In intact animals, hypoxia increased activity; however, greater
      increases in activity levels followed CSD, while vagotomy elicited a marked
      reduction of the response. Thus, carotid body afferents exert inhibitory or
      disfacilitatory influences on intermediate area neurons, while the vagus appears
      to play an excitatory role.

PMID- 7816344
TI  - Effects of diabetes on spontaneous locomotor activity in mice.
AB  - Spontaneous locomotor activity in diabetic mice was significantly greater than
      that in non-diabetic mice. Haloperidol and SCH23390, a selective dopamine D1
      receptor antagonist, significantly reduced spontaneous locomotor activity in
      diabetic mice, but not in non-diabetic mice. Spontaneous locomotor activity in
      diabetic mice was also reduced by pretreatment with naltrindole, a selective
      delta-opioid receptor antagonist, and 7-benzylidenenaltrexone, a selective delta1
      opioid receptor antagonist. The rate of dopamine turnover in the limbic forebrain
      in diabetic mice was significantly higher than that in non-diabetic mice. These
      findings suggest that the enhanced spontaneous locomotor activity in diabetic
      mice may result from increased dopamine neurotransmission, which might be due to
      an increase in dopamine release in mesolimbic dopamine systems. The increased
      dopamine neurotransmission in diabetic mice may also be due to the up-regulation
      of delta-opioid receptor-mediated functions.

PMID- 7816346
TI  - Effects of soman on cerebral astrocyte plasma membranes: a freeze-fracture study.
AB  - Astrocytes are identifiable on freeze-fracture by regular geometric aggregates of
      uniform intramembranous particles (IMP), the 'orthogonal arrays' (OA). These OAs
      are considered to be potassium channels that maintain the ionic balance around
      neurons. After subcutaneous administration of a single near LD50-dose of soman in
      rats, neurotoxic epileptogenic irreversible cholinesterase inhibitor, replicas
      showed a significant decrease in OA density in the convulsed animals. This
      dissociation by soman confirms that OA are a particularly labile membranes
      specialization. Frequent clumping of IMP and numerous cleavage planes were
      observed; this could be the result of an interaction between the liposoluble
      poison and membrane phospholipid fluidity.

PMID- 7816347
TI  - Immunodetection of putative imidazoline receptor proteins in the human and rat
      brain and other tissues.
AB  - A specific anti-imidazoline receptor (IR) protein antiserum was used to detect
      these putative receptors in brain and other tissues. In immunoblotting
      experiments, various brain areas and tissues expressed a double band of 29-30
      kDa, and some of them bands of 47 and 66 kDa. The human medulla oblongata also
      showed bands of 44 and 50 kDa; and the rat adrenal medulla, bands of 58 and 86
      kDa. Total immunoreactivity correlated with the density of IR binding sites in
      the various tissues. This is first evidence of heterogeneity of immunoreactive
      IRs in the mammalian brain.

PMID- 7816348
TI  - Effects of bifemelane on parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) in the common marmoset.
AB  - The effects of bifemelane on parkinsonism were shown in MPTP-treated common
      marmosets. The administration of bifemelane increased locomotor activity in MPTP
      treated marmosets but not in normal control marmosets. In a microdialysis study,
      extracellular levels of dopamine and its metabolites increased following the
      administration of bifemelane. These results indicate that it is worth studying
      the effects of bifemelane hydrochloride on patients with Parkinson's disease.

PMID- 7816349
TI  - Biphasic effect of ethanol on extracellular accumulation of glutamate in the
      hippocampus and the nucleus accumbens.
AB  - The effect of systemic ethanol administration on the extracellular levels of
      glutamate in the hippocampus and nucleus accumbens of conscious rats was assessed
      using microdialysis. At 0.5 g/kg, ethanol caused a sustained increase in the
      levels of glutamate in both regions. Following 1.0 g/kg, response was observed in
      the nucleus accumbens while a trend towards a decrease in glutamate levels
      occurred in hippocampus. Injection of 2.0 g/kg ethanol decreased these levels in
      both regions. These findings suggest a relationship between the previously
      reported biphasic behavioral consequence of ethanol and its effect on
      glutamatergic neurotransmission.

PMID- 7816351
TI  - The nutrition implications of cardiac cachexia.
AB  - Weight loss is a frequent sequela in patients with congestive heart failure and
      is commonly referred to as cardiac cachexia. This weight loss is unlike that seen
      in simple starvation because it preferentially involves the depletion of lean
      body mass. In addition, the presence of cardiac cachexia can have profound
      clinical implications for patients in terms of complications, clinical outcome,
      and overall cost. The mechanism for the alterations in body composition is
      multifactorial, but a major cause may be the cytokine-mediated host response to
      the underlying disease. This article reviews the syndrome of cardiac cachexia in
      light of recent evidence regarding the role of cytokines, as well as potential
      therapies.

PMID- 7816350
TI  - Lecithin and choline in human health and disease.
AB  - Choline is involved in methyl group metabolism and lipid transport and is a
      component of a number of important biological compounds including the membrane
      phospholipids lecithin, sphingomyelin, and plasmalogen; the neurotransmitter
      acetylcholine; and platelet activating factor. Although a required nutrient for
      several animal species, choline is not currently designated as essential for
      humans. However, recent clinical studies show it to be essential for normal liver
      function. Additionally, a large body of evidence from the fields of molecular and
      cell biology shows that certain phospholipids play a critical role in generating
      second messengers for cell membrane signal transduction. This process involves a
      cascade of reactions that translate an external cell stimulus such as a hormone
      or growth factor into a change in cell transport, metabolism, growth, function,
      or gene expression. Disruptions in phospholipid metabolism can interfere with
      this process and may underlie certain disease states such as cancer and
      Alzheimer's disease. These recent findings may be appropriate in the
      consideration of choline as an essential nutrient for humans.

PMID- 7816352
TI  - Children with congenital heart disease: a nutrition challenge.
AB  - Growth in children with congenital heart disease (CHD) is often compromised. For
      several decades, investigators have tried to identify the factors affecting
      growth in children with CHD. Cardiac malformations are undoubtedly responsible
      for malnutrition, which may range from mild undernutrition to severe failure to
      thrive (FTT). Malnutrition may then significantly undermine the outcome of
      corrective surgical operations and postoperative recovery. Mechanisms linking CHD
      to malnutrition may be related either to decreased energy intake and/or to
      increased energy requirements. Decreased energy intake can involve deficiencies
      of specific nutrients, or insufficient total caloric intake. Increased
      respiratory rate accompanying congestive heart failure may be responsible for
      increased energy requirements. Different types of cardiac malformations and
      consequent interventions may have different effects on growth and require diverse
      strategies. Most treatment strategies aim to facilitate "catch-up" growth,
      providing extra calories and protein that exceed the Recommended Dietary
      Allowance for age. However, there is no generally accepted set of guidelines that
      define appropriate caloric intake for catch-up growth. We attempt to identify the
      most important causes of malnutrition and highlight the most effective nutrition
      strategies for children with CHD.

PMID- 7816353
TI  - Carbohydrate versus fat in the dietary treatment of short-bowel syndrome.
AB  - The importance of the human colon in energy salvage has been documented again in
      a recent clinical study. Patients with short-bowel syndrome can be divided into
      two groups: those with colon and those without colon in continuity. While a high
      carbohydrate, low-fat diet appears to be of nutritional benefit to the former
      group, dietary restrictions and reduction of fat intake are not effective in
      reducing intestinal energy loss in the latter group.

PMID- 7816354
TI  - Uptake of retinoids by adipose tissue.
AB  - Adipose tissue was found to contain considerable amounts of retinoids and retinol
      binding protein mRNA, particularly in epididymal and perinephric depots. Delivery
      of retinoids appears to be through the hydrolysis of retinyl esters in
      postprandial chylomicrons by lipoprotein lipase, with subsequent uptake of
      retinol by adipocytes.

PMID- 7816355
TI  - Should lactating women exercise?
AB  - The safety of recreational exercise for lactating mothers has been examined in a
      prospective, intervention study. Thirty-three women, who were 6-8 weeks
      postpartum and breast-feeding exclusively were randomly chosen to join either an
      exercise or a control group. The exercise group took part in a program of aerobic
      activities averaging 4.5 sessions per week. After 12 weeks, aerobic capacity was
      significantly higher in the women who had exercised than in the controls, but no
      differences in body weight, body fatness, energy expenditure, or resting
      metabolic rate (RMR) were noted. The exercise program had no effect on breast
      milk output or composition or infant weight gain. This demonstrates that
      recreational exercise sufficient to improve cardiovascular fitness without
      substantially altering energy balance does not adversely affect lactation
      performance.

PMID- 7816356
TI  - Maximal genetic potential for adult stature: is this aim desirable? (Nutr Rev
      1994; 52:208-10)

PMID- 7816358
TI  - Cancer detection by physical examination. Breast and pelvic organ examination.

PMID- 7816357
TI  - Implementing the Put Prevention into Practice program.
AB  - Put Prevention into Practice (PPIP) is a national program designed to improve the
      delivery of preventive care to patients by all primary care clinicians. It covers
      the full range of clinical preventive services, including immunizations,
      screening tests, chemoprophylaxis, and counseling interventions. The materials
      that comprise this program involve patients, office/clinic systems and staff, and
      clinicians, including nurse practitioners. The need for preventive care, the
      barriers to be overcome, the PPIP program, and a strategy for its implementation
      are delineated. Principles for successful implementation include: high level
      administrative support, ownership by all the players in the implementation
      process, a person designated to manage implementation, and an ongoing
      evaluation/auditing process that provides feedback to clinicians and others
      participating in the program.

PMID- 7816359
TI  - Parenting confidence during toddlerhood. A comparison of mothers and fathers.
AB  - Previous research has shown the Toddler Care Questionnaire (TCQ) to be a valid
      measure of parenting confidence among mothers of toddlers. However, there is no
      evidence demonstrating the validity of the TCQ among fathers of toddlers. The
      purposes of this study were to 1) examine the reliability and validity of the TCQ
      among fathers of 12- to 36-month old children and 2) compare the childrearing
      topics mothers and fathers identify as those for which they would like
      information. Forty-six married mothers and fathers (n = 92) completed the TCQ,
      three measures of child behavior, and a measure of parental depression. Maternal
      confidence was related to depression and all measures of child behavior. Paternal
      confidence was related only to the intensity of the child's behavior. Mothers
      requested more than twice the amount of childrearing information than did fathers
      although there were similarities in the types of information requested. The data
      support the validity of the TCQ and its clinical utility among fathers of
      toddlers although different factors appear to affect parenting confidence among
      mothers and fathers.

PMID- 7816360
TI  - The importance of the early detection of varicocele in adolescent males.
AB  - Varicocele is a common finding in adult and adolescent males and may lead to
      potential infertility. Many methods are available to the practitioner for
      evaluation of the problem. The least invasive is color duplex imaging of the
      spermatic vein, to visualize the presence of reflux (backflow) in the vein, as
      well as to define flow characteristics. It is recommended that adolescent males
      be screened using this modality beginning at age 10-15 years if they appear to
      have physical findings indicating a varicocele or if there is a family history of
      male fertility problems or varicocele. If a varicocele is found, then referral
      can be made for intervention if needed.

PMID- 7816361
TI  - Care of the newly-diagnosed HIV positive patient.

PMID- 7816363
TI  - The effectiveness of an employee incentive prenatal education program in
      reduction of premature births and healthcare costs.

PMID- 7816362
TI  - An update on non-Hodgkin's lymphomas.
AB  - The non-Hodgkin's lymphomas are a diverse group of diseases characterized by
      enlargement of the lymph nodes and are indolent or aggressive. The
      histopathologic subtype provides the best guide to the nature of these diseases.
      In most patients the etiology is unknown. Painless peripheral adenopathy is the
      usual presenting feature. A careful clinical staging without laparotomy is
      recommended to establish disease extent, prognosis and treatment. In patients
      with indolent (low grade) lymphomas, a period of observation prior to treatment
      may be appropriate if the patient is asymptomatic. Symptomatic patients with low
      grade lymphoma require therapy. For patients with aggressive disease
      (intermediate or high grade), immediate treatment with curative intent is
      indicated. High dose therapy with bone marrow transplantation may be used to cure
      a small number of patients who relapse following initial chemotherapy.

PMID- 7816364
TI  - Nurses need certification as well as licensure.

PMID- 7816365
TI  - Role differentiation of the nurse practitioner and physician assistant, within
      the realization of health care reform.

PMID- 7816366
TI  - Nurse practitioners stand for choice in health care.

PMID- 7816367
TI  - Venlafaxine: a new antidepressant drug.

PMID- 7816368
TI  - Rimantadine for influenza A prevention and treatment.

PMID- 7816369
TI  - Guidelines for clinical preventive services. Essential for nurse practitioners in
      practice, education, and research.
AB  - Guidelines for clinical preventive services, including counseling, screening, and
      immunizations, are important to nurse practitioner practice, education, and
      research. Delivery of clinical preventive services can be improved by the use of
      evidence-based guidelines, which provide recommendations on what services should
      be provided and who should receive them. Development of guidelines by the U.S.
      Preventive Services Task Force is discussed, as well as principal findings that
      evolved from their deliberations. The authors provide a rationale and options for
      the development of nursing guidelines for clinical preventive services.
      Implementation of guidelines can be facilitated by use of the "Put Prevention
      Into Practice" materials.

PMID- 7816370
TI  - Screening for adolescent idiopathic scoliosis. Policy statement. U.S. Preventive
      Services Task Force.

PMID- 7816371
TI  - Current therapies and prophylaxis of malaria.
AB  - Malaria is a potentially life-threatening disease. Although not commonplace in
      the United States, malaria cases are occurring more frequently due to an influx
      of military personnel returning from duty in malarious areas, increased numbers
      of immigrants, and tourist and business travel to endemic areas. Careful history
      taking and proper laboratory diagnosis are essential in detecting malaria.
      Malaria should be considered in the differential diagnosis with any fever of
      unknown origin. Due to the increase in chloroquine resistant P. falciparum
      malaria worldwide it behooves the clinician to keep abreast of current therapies
      in the treatment and prophylaxis of malaria. The Centers for Disease Control and
      Prevention is one of the best resources for up-to-date recommended therapies.

PMID- 7816372
TI  - Resolution of hot issues necessitate National Nurse Practitioner Organization.

PMID- 7816373
TI  - Preparing and presenting testimony. Guidelines for the health care practitioner.
AB  - Whether presenting to Hillary Rodham Clinton's Health Care Reform Task Force, or
      as citizens presenting to a Board of Selectmen on issues affecting the Council on
      Aging, health providers possess a unique and valuable perspective that few
      policymakers or politicians have. The health practitioner's role as a direct
      provider of health services, advocate, educator, role model, policymaker,
      clinician, researcher, consultant, collaborator, administrator, and counselor [1]
      can be combined to influence policy and policymakers through formal testimony
      preparation and presentation. Presenting testimony for public hearings is an
      effort to influence public policy. The purpose of this article is to provide
      guidelines which will encourage increased legislative involvement on the part of
      health providers. Those willing to be involved in local, regional, state, or
      national government activities by providing testimony may effect needed change.

PMID- 7816374
TI  - Spasmodic dysphonia: new diagnosis and treatment opportunities.
AB  - The ability to communicate is a basic need. Spasmodic dysphonia, a rare dystonia
      focal to the larynx, affects the vocal muscles resulting in abnormal sound and
      speech production. The voice may become hoarse, strained, strangled, tremulous,
      whispered, or aphonic. Lack of appropriate diagnosis along with the continued use
      of an abnormal voice often results in frustration, anxiety, and depression.
      Improved diagnostic ability and unique treatment with botulinum toxin injection
      (Botox) are now available to patients in several large medical centers across the
      United States and Canada. A knowledgeable and observant health care provider can
      alert patients and families to the possibility of treatment for a chronic voice
      disturbance.

PMID- 7816375
TI  - Perimenopause and heavy menstrual flow: standard treatments and alternative
      treatment modalities.

PMID- 7816376
TI  - Vaginal health effects of tampon use: implications for vaginitis.

PMID- 7816377
TI  - Graphical analysis of dynamic data: the Patlak-Rutland plot.

PMID- 7816378
TI  - Gamma camera renography with 99Tcm-DTPA: the impact of variations in input plasma
      curve on estimated GFR.
AB  - In an attempt to improve the reliability in estimating glomerular filtration rate
      (GFR) from gamma camera renography without blood sampling, we have investigated
      the impact of plasma input region of interest (ROI) size and location and the
      effect of the time delay between the circulation peak in the renal curves and in
      the plasma curve. An uptake index (UI) was calculated using plasma ROIs of five
      different sizes (8-56 cm2) and compared with measured 51Cr-EDTA clearance. The
      spread of the estimated GFR was not affected by the variations in plasma ROI size
      but different relations were obtained between UI and GFR. The plasma ROI markedly
      affected the estimated GFR (a deviation of 3.5 cm from the maximal region led to
      an overestimation of the GFR of 36%). Furthermore, the most reliable GFR estimate
      (S.D. 10.5 ml min-1) was achieved by including the whole circulation peak in the
      calculation time interval of the time delay-adjusted renogram, except the first
      frame. The time delay adjustment also enabled the calculation of a factor alpha,
      which represents the ratio between the blood volume within the renal ROI and that
      within the plasma input ROI. An abnormal alpha/UI ratio would suggest an
      unreliable GFR estimation.

PMID- 7816381
TI  - Reliability of data obtained by radionuclide angiocardiography in follow-up
      studies with special reference to intra- and interobserver variations.
AB  - The reproducibility of the data obtained by radionuclide angiocardiography was
      studied in terms of the intra- and intervariations of three technicians. Three
      parameters were chosen: the left ventricular ejection fraction (LVEF), the 1/3
      filling fraction (1/3FF), and the ratio of the time from end systole to the point
      of peak filling rate against the entire diastolic period (TRPFR). First, each
      technician studied an independent consecutive series of 40 patients for the
      initial analysis. The original data of each patient, composed of 26 frames for
      one beat, were stored on an optical disc for the intra- and intervariation
      studies. In this study, analysis of the volume curve was performed by using both
      3rd order and 4th order Fourier series. The region of interest (ROI) for the left
      ventricle, which was set for the initial analysis, was recorded by Polaroid
      photography to be used as a reference for the later analyses for the variation
      studies. The least variation was noted in the LVEF not only for the
      intravariation study but also for the intervariation study, no matter which order
      of the Fourier series was used. However, the 3rd order Fourier series seemed to
      give better curve fitting to avoid fluctuation of the diastolic parameters. The
      results indicate that we can expect more steady and reliable information from
      LVEF than from the diastolic parameters, even when various technicians perform
      the follow-up study of a particular patient.

PMID- 7816380
TI  - Relationship between various parameters derived from 123I-labelled beta-methyl
      branched fatty acid whole-body scintigraphy and left ventricular ejection
      fraction in patients with ischaemic heart disease.
AB  - Heart uptake and clearance of 123I-15-(p-iodophenyl)-3(R,S)-methyl- pentadecanoic
      acid (BMIPP) by whole-body scintigraphy in relation to left ventricular ejection
      fraction (LVEF) was evaluated in 34 patients with ischaemic heart disease. At 45
      and 210 min after injection, anterior whole-body images were obtained. In each
      patient, multigated blood pool scintigraphy was also performed, and LVEF was
      calculated. The percentage heart uptake of BMIPP did not have a significant
      correlation with LVEF (R = -0.299, NS). In contrast, there was a positive
      correlation between LVEF measured by multigated blood pool scintigraphy and BMIPP
      count density of the heart (R = 0.467, P = 0.005). Myocardial BMIPP washout rate
      also positively correlated with LVEF (R = 0.472, P = 0.005). In addition to these
      observations, there was a positive correlation between the BMIPP count density of
      the heart and myocardial BMIPP washout rate (R = 0.0543, P = 0.001). Thus, the
      BMIPP count density of the heart and myocardial BMIPP washout rate derived from
      BMIPP whole-body scintigraphy directly correlated with LVEF. However, the
      correlations between these parameters and LVEF were not strong enough to allow
      left ventricular dysfunction to be assessed precisely.

PMID- 7816379
TI  - 99Tcm-MAG3 renogram deconvolution in normal subjects and in normal functioning
      kidney grafts.
AB  - This study provides values of transit times obtained by 99Tcm- mercaptoacetyl
      triglycine (99Tcm-MAG3) renogram deconvolution for both normal subjects and
      kidney graft recipients. The analysis included 50 healthy kidney units from 25
      volunteers and 28 normal functioning kidney grafts. The parameters calculated for
      the whole kidney (WK) and for the renal parenchyma (P) were: mean transit time
      (MTT) and times at 20% (T20) and 80% (T80) of renal retention function initial
      height. For healthy kidneys the WK MTT was 174 +/- 27 s and P MTT 148 +/- 22 s.
      The WK T20 values were 230 +/- 33 s and P T20 231 +/- 34 s. The WK T80 was 108 +/
      19 s and P T80 106 +/- 12 s. Whole kidney and parenchymal values of transit
      times for normal functioning kidney grafts do not present significant differences
      with respect to healthy kidneys.

PMID- 7816382
TI  - Left ventricular function and myocardial perfusion during dipyridamole infusion
      assessed by a single injection of 99Tcm-sestamibi in patients unable to exercise.
AB  - First-pass radionuclide ventriculography followed by myocardial single photon
      emission computed tomography (SPECT) with 99Tcm-methoxyisobutyl isonitrile
      (sestamibi) was performed at rest and during dipyridamole infusion in 42 patients
      with suspected coronary artery disease. The presence of coronary stenoses of > or
      = 50% diameter was compared with the presence of rest or dipyridamole-induced
      abnormalities in perfusion or left ventricular function. Radionuclide-determined
      left ventricular ejection fraction (LVEF) was highly reproducible and correlated
      well with LVEF derived from contrast left ventriculography. Left ventricular
      ejection fraction decreased significantly after dipyridamole infusion in patients
      with multivessel disease (58 +/- 10% versus 52 +/- 11%, P < 0.01). The
      sensitivity and specificity for the detection of patients with coronary artery
      disease were 85 and 75% by myocardial SPECT, and 47 (P < 0.01 versus SPECT) and
      75% by LVEF, respectively. However, in patients with multivessel disease, the
      sensitivity of LVEF was not different from that of SPECT (72% versus 89%, P =
      ns). The sensitivity of LVEF was higher in patients with multivessel disease than
      in those with single-vessel disease (19% versus 72%, P < 0.01). Radionuclide
      ventriculography followed by myocardial SPECT with 99Tcm-sestamibi allows
      simultaneous evaluation of ventricular contractile function associated with
      perfusion abnormality during dipyridamole infusion and may enhance the functional
      description of myocardial ischaemia.

PMID- 7816383
TI  - Determination of split renal function from gamma camera renography: a study of
      three methods.
AB  - Three different methods for calculation of the split kidney function from gamma
      camera renography with 99Tcm-DTPA are surveyed in this study, the integral, the
      slope and the uptake index methods. The reproducibility in calculating the
      relative renal function was very good with all three methods (coefficient of
      variation 2-4%). Single kidney glomerular filtration rate (GFR) was assessed by
      the three methods and 51Cr-EDTA clearance prior to nephrectomy, giving the
      accuracy of each method. The slope and uptake index methods showed high accuracy
      (0.9-2.0 ml min-1), while it is significantly reduced with the integral method
      (4.6 ml min-1), compared to the postoperative 51Cr-EDTA clearance. The uptake
      index method enables calculation of a ratio between the kidneys (alpha/UI)SR,
      which relates each kidney's intrarenal blood volume (alpha) to its renal function
      (UI). This ratio was compared in a group consisting of 38 patients with kidney
      tumours and in a control group of 32 patients. It was rather constant in the
      control group but significantly higher and within a wider range in the group with
      renal tumours. These discrepancies may indicate an abnormal intrarenal blood
      volume. Furthermore, the correlation between results assessed by the three
      calculation methods in the control group was good, while the correlation in the
      group with renal tumours deteriorated.

PMID- 7816384
TI  - 131I-MIBG as a first-line treatment in high-risk neuroblastoma patients.
AB  - The observed response to 131I-metaiodobenzylguanidine (MIBG) therapy in advanced
      neuroblastoma after conventional therapy, the non-invasiveness of the procedure,
      and the high metabolic activity which is frequently observed in untreated tumours
      led to the concept of substituting 131I-MIBG therapy for combination chemotherapy
      at diagnosis prior to surgery in patients with advanced disease/high-risk
      neuroblastoma. The objective of introducing 131I-MIBG therapy as the first
      therapy in the treatment schedule is to reduce the tumour volume, enabling
      adequate (> 95%) surgical resection of the tumour and to avoid toxicity and the
      induction of early drug resistance. The advantages of this approach are that the
      child's general condition is unaffected or improved before it undergoes surgical
      resection and that chemotherapy is reserved to treat minimal residual disease
      postoperatively. Thirty-one children who presented with inoperable neuroblastoma
      (10 Evans stage III, 21 stage IV) were treated according to this protocol. The
      objective response to the 131I-MIBG therapy at diagnosis with respect to the
      volume of the primary tumour, the metastases and catecholamine excretion in urine
      varied from 72 to 81%, which is better than after conventional treatment.
      Nineteen of 27 evaluable patients (70%) had complete or > 95% resection of the
      primary tumour or did not require surgery at all. Only 11 of 31 patients
      developed isolated thrombocytopenia and, despite the fact that the bone marrow
      was invaded in 16 patients, moderate bone marrow depression occurred in only two
      cases.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7816385
TI  - Stabilization and multidose use of exametazime for cerebral perfusion studies.
AB  - The efficient use of exametazime for cerebral blood flow imaging is restricted by
      the short useful life of the reconstituted kit due to the instability of the
      primary complex. It is therefore recommended that 99Tcm-exametazime be used
      within half an hour after preparation allowing only a single patient dose to be
      prepared from one vial of exametazime. The shelf-life of 'cold' reconstituted
      exametazime has been extended by means of stannous enhancement. Freshly prepared
      stannous fluoride solution, 0.8 ml (5.4 micrograms SnF2), was mixed with 0.5 ml
      (42 micrograms) exametazime solution followed by the addition of up to 1500 MBq
      pertechnetate. The radiochemical purity of the chelate was 91% (S.D. 3.6%, n =
      3). The rate of conversion of the primary complex (kc = 0.012 +/- 0.011 h-1) was
      considerably slower than the rate of degradation obtained using the recommended
      method of preparation (kc = 0.17 +/- 0.02 h-1). Radiochemical purity levels
      greater than 80% were maintained for up to 2.5 h after preparation and the level
      of free pertechnetate did not exceed 7%. There was only a slight deterioration of
      the cold reconstituted exametazime on storage of 0.3 +/- 0.1% per day. However,
      exametazime reconstituted up to 3 weeks previously produced more than 80% purity.
      The mean radiochemical purity obtained in 22 studies was 90% with a range of 81
      98%. Clinical validation was performed in a blinded study of 38 patients using
      single photon emission computed tomography (SPECT). There was no significant
      difference between the images obtained using the tin enhancement method of
      preparation and the manufacturer's method (chi 2 = 3.62, P = 0.16).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7816386
TI  - A novel method for labelling human immunoglobulin-G with 99Tcm suitable for
      inflammation scintigraphy.
AB  - An amount of 1.0 mg human immunoglobulin G (hIgG) treated with ascorbic acid at a
      molar ratio of 1:5000 for 16 h at 4-7 degrees C was mixed with 250 micrograms GHA
      and 5 micrograms stannous chloride dihydrate in normal saline. Radiolabelling of
      hIgG (> 98%) was achieved instantly when mixed with 99Tcm-pertechnetate. The
      preparation was sufficiently stable in serum at 37 degrees C. The competitive
      binding assay and gel electrophoresis of the native and reduced hIgG did not show
      any measurable loss in immunoreactivity and intactness due to its reduction.
      There was no significant decrease in the radiolabel of labelled hIgG when
      incubated with diethylenetriaminepentaacetate (DTPA) (50-fold), in contrast with
      about 9% loss of the radiolabel by treating it with a similar concentration of
      cysteine. Blood clearance of labelled hIgG in rabbits was biphasic with about 78
      min and 8 h as T1/2 of the fast and slow phases. Biodistribution of the
      radiotracer in mice at 4 h showed its uptake by liver (10.2%), kidneys (5.39%),
      intestines (7.33%) and muscles (3.9%), which altered to 5.63, 3.20, 4.03 and
      6.73%, respectively, at 24 h. The radiotracer was excreted through both renal and
      hepatobiliary routes. High accumulation of the radiolabelled hIgG in inflammatory
      lesions of the patients confirmed the clinical usefulness of the method
      developed.

PMID- 7816387
TI  - Effect of different anticoagulants on the labelling of red blood cells and plasma
      proteins with 99Tcm.
AB  - There are controversies about the effect of different anticoagulants on the
      labelling of blood elements with 99Tcm. Our results show that the type of
      anticoagulant employed to withdraw the whole blood can modify the 99Tcm labelling
      of red blood cells (RBC) and plasma proteins (PP). The anticoagulants ACD (citric
      acid, sodium citrate and dextrose solution), heparin and sodium oxalate present
      similar results for the 99Tcm labelling of RBC with the exception of 0.13 microM
      stannous chloride. In this assay oxalate provides the best RBC labelling. In
      addition, with ethylenediaminetetraacetic acid (EDTA) the labelling of RBC is
      almost always lower than with the other anticoagulants, probably due to its high
      chelating capacity. The anticoagulants ACD, oxalate and heparin show the same
      results as expected with 99Tcm labelling of PP. The lowest labelling at 13.00
      microM stannous chloride in the presence of oxalate is probably due to its low
      chelating capacity. The results also reinforce the idea that the erythrocyte
      membrane exerts an important role in the regulation of stannous ion transport
      into RBCs.

PMID- 7816388
TI  - Evaluation of gallbladder function by quantitative radionuclide cholescintigraphy
      in patients with gallbladder sludge or stones.
AB  - Thirteen patients with gallbladder sludge, 14 patients with gallstones and 24
      control cases with normal gallbladders were included in the study. Gallbladder
      function was represented as the filling fraction (FF) and the ejection fraction
      (EF) calculated using quantitative 99Tcm-DISIDA cholescintigraphy and compared in
      the groups. The results showed that (1) the patients with normal gallbladders had
      the highest FF and EF, (2) those with gallstones had the lowest FF, (3) the
      patients with gallbladder sludge had the lowest EF, and (4) the coefficient of
      variation (CV) of FF and EF of the normal controls were less than those for the
      patients with gallstones or sludge. There was only a statistically significant
      difference between the normal controls and the patients with gallstones for FF.
      However, no significant differences existed among the three groups for EF. In our
      preliminary results, we found that gallbladder sludge or stones may impair
      gallbladder function, especially FF, as evidenced by noninvasive and quantitative
      99Tcm-DISIDA cholescintigraphy, and the higher CV value suggests that gallbladder
      function in patients with gallstones or sludge is more variable.

PMID- 7816389
TI  - Reporting of perfusion/ventilation lung scintigraphy using an anatomical lung
      segment chart: a prospective study.
AB  - This study prospectively evaluated the effect of the consistent use of a
      previously described anatomical lung segment chart on the interpretation of lung
      scans. Simultaneous perfusion/ventilation lung scintigraphy was performed in 221
      consecutive patients with clinically suspected pulmonary embolism. Lung scans
      were immediately reported as normal, high probability or non-diagnostic with the
      use of an anatomical lung segment chart. After at least 6 months, blinded lung
      scans were randomly read by a panel of nuclear medicine physicians. Initial lung
      scan reports were classified as normal, high probability or non-diagnostic in 64,
      63 and 94 patients, respectively. Overall observer disagreement was 5.9% (95%
      confidence interval (CI) 3.2-9.8%), while this was 7.8, 3.2 and 7.9% for lung
      scans that were initially reported as normal, non-diagnostic and high
      probability, respectively. Reclassification consisted of normal to non-diagnostic
      (5), non-diagnostic to normal (1), non-diagnostic to high probability (2), and
      high probability to non-diagnostic scan results (5). From the literature, an
      overall disagreement of 20% was expected if no chart had been used. In
      conclusion, this study confirms that the consistent use of a lung segment chart
      reduces observer disagreement in the reporting of lung scans.

PMID- 7816391
TI  - Evaluation of the factors affecting the accuracy and precision of a technique for
      quantification of volume and activity in SPECT.
AB  - The use of the technique of maximization of interclass variance to determine the
      threshold level defining the volume of an object in single photon emission
      computed tomography (SPECT) and hence its activity has been evaluated in a
      variety of conditions. The influence of varying activity on volume assessment and
      varying volume on activity assessment were shown to be negligible. The effect of
      object shape for the range of shapes likely to be found in the body was also
      small. Non-uniformity of activity in the object caused an underestimation of
      volume and to a lesser extent its activity. However, with activity varying by
      100% within the volume, volume was only underestimated by 10% and activity by 3%.
      The presence of activity surrounding the object caused an overestimation of
      volume which increased linearly with the relative level of surrounding activity.
      The object to surrounding activity concentration ratio could be estimated and
      therefore its effect corrected. The influence of nearby objects and methods of
      dealing with their effect on the technique are described. Activity concentrations
      in objects with uniform distribution assessed using total activity divided by
      total volume were shown to be more accurate than assessments from maximum voxel
      count rate for objects with a volume below 150 ml.

PMID- 7816392
TI  - Radiolabelling of monoclonal antibodies.

PMID- 7816390
TI  - Detection of norepinephrine distribution in rats with adrenal medulla
      autotransplants using 125I-meta-iodobenzyl guanidine.
AB  - The viability of autologous adrenal medullary transplants was evaluated using
      125I-meta-iodobenzyl guanidine (MIBG), an adrenal medullary scanning agent.
      Bilateral cavities in the caudate nuclei were made stereotaxically in Wistar
      rats. One week later, the left adrenal medulla was resected by microsurgery,
      followed by reoperation of the cranium and implantation of a 0.5-1.0 mm diameter
      fragment of the adrenal medulla into the right caudate nucleus. Six weeks after
      the second operation, MIBG was administered intravenously. Specimens from both
      cerebral hemispheres, from the right adrenal medulla and blood were analysed by
      radioactivity counting. The radioactivity present in the blood of the
      transplanted group of 11.40 +/- 2.35 cpm mg-1 (mean +/- S.E.M.) was significantly
      higher than in the control group of 4.97 +/- 1.16 cpm mg-1 (P < 0.05).
      Radioactivity present in the right hemisphere of the transplanted group was 0.66
      +/- 0.03 cpm mg-1, also significantly higher than in the control group which was
      0.47 +/- 0.04 cpm mg-1 (P < 0.01). Autoradiography revealed increased
      radioactivity in the area of the transplants, which was also confirmed
      histologically.

PMID- 7816393
TI  - Question of the month--April 1994. Stress 201Tl SPET.

PMID- 7816394
TI  - Physician identification of battered women.

PMID- 7816395
TI  - Reproductive toxicology of alkylating agents.
AB  - Alkylating agents have been used during childhood and in reproductive age groups
      for the treatment of malignancy or collagen-vascular disease. Because of their
      mechanism of action, alkylating agents have the ability to interfere with
      chromosomal structure, ovarian function, spermatogenesis, and embryogenesis.
      Teratogenic risks have been established in animal studies, although are less
      clear for humans. Total dose, timing of administration, and age of the patient at
      the time of therapy are all factors in determining adverse effects. If possible,
      alkylating agents should be avoided in the first trimester, but can be used
      during the remainder of pregnancy.

PMID- 7816396
TI  - Management of apparently isolated fetal ventriculomegaly.
AB  - Early ultrasound examination can provide accurate antenatal diagnosis of many
      fetal congenital abnormalities but it is often difficult to translate this into
      prognosis because of the variable functional effects of similar anatomical
      changes. In the case of isolated fetal ventriculomegaly it is the prognosis that
      parents require in order to choose between continuing with the pregnancy or
      termination. The outcome for antenatally diagnosed ventriculomegaly seems to be
      worse than that reported in the neurosurgical literature for children treated
      with congenital hydrocephalus. Follow-up is available for 276 cases with
      apparently isolated ventriculomegaly who did not undergo termination of
      pregnancy. One hundred ninety-four (70 per cent) survived and of these 114 (59
      per cent) had normal developmental quotient to follow-up. Intrapartum
      cephalocentesis to aid vaginal delivery is almost invariably associated with
      fetal/neonatal death. A favorable outcome of normal mental development is present
      in cases with borderline, stable (nonprogressive) isolated ventriculomegaly or
      cases in which ventriculomegaly has resolved in utero. Fetal surgery would seem
      to offer no benefit. The outcome is much worse when other associated congenital
      anomalies are present.

PMID- 7816397
TI  - Incidence, risk factors, and prevention of poststerilization regret in women: an
      updated international review from an epidemiological perspective.
AB  - Tubal sterilization is the world's most commonly used contraceptive method. Even
      a small proportion of women incurring poststerilization regret would translate
      into a large number of sufferers. In this review, we examine recent reports on
      the incidence of, and the risk factors for, posttubal sterilization regret in
      women and requests for sterilization reversal in both developed countries and
      less-developed countries. We also consider the implications of our findings in
      the practical prevention of poststerilization regret and requests for
      sterilization reversal, and discuss methodological issues.

PMID- 7816398
TI  - Counting the cost of HIV/AIDS prevention.

PMID- 7816399
TI  - Measuring how well we do?

PMID- 7816400
TI  - The challenge of going it alone.

PMID- 7816401
TI  - Self-auditing the OHP's ethical performance.

PMID- 7816402
TI  - Competence for beginners.

PMID- 7816403
TI  - Role of the obstetrician/gynecologist in the management of breast disease.
AB  - The obstetrician/gynecologist is the primary physician to women. The breast is an
      organ of reproduction, and complete breast examination is part of the obstetric
      and gynecologic examination. In addition to history and physical examination, the
      obstetrician/gynecologist should be prepared to undertake simple diagnostic
      studies. Cancer, on the other hand, presents a number of challenges. The
      appropriate role for the obstetrician/gynecologist is one of surveillance and as
      a resource for patients, including the discussion of risk factors and treatment
      alternatives.

PMID- 7816404
TI  - Functional anatomy and physiology of the female breast.
AB  - As mammals, we define our biologic class by the function of the breast in
      nourishing our young. As obstetricians, we seek to enhance or diminish function;
      as gynecologists, the appearance of inappropriate lactation (galactorrhea) may
      signify serious disease. In this article, development, differentiation, and
      functional anatomy of the breast is discussed. The hormonal interactions
      responsible for these events and the physiologic function of this vital
      reproductive organ during the life cycle of the woman is emphasized.

PMID- 7816405
TI  - Fibrocystic changes.
AB  - Most women have fibrocystic changes in their breasts. Patients with proliferative
      changes with atypia are at an increased risk of breast cancer. The management of
      mastalgia is the challenge most frequently encountered in patients with
      fibrocystic changes. Clinically, the types and variants of fibrocystic changes
      are sometimes difficult to distinguish. When the diagnosis of fibrocystic changes
      is unclear, a histologic evaluation biopsy, open surgical biopsy, should be
      performed.

PMID- 7816406
TI  - Nipple discharge.
AB  - The evaluation and management of nipple discharge can be undertaken with minimal
      difficulty by performing a careful history and examination and following a
      logical thought process in linking the type of discharge with the suitable mode
      of treatment. In this manner, the patient's discharge can be efficiently and
      thoroughly evaluated.

PMID- 7816407
TI  - Mastodynia.
AB  - The most important factors in the evaluation and treatment of breast pain consist
      of a thorough history, physical, and radiologic evaluation. These can be used to
      reassure the patient that she does not have breast cancer. In the 15% of
      mastalgia patients who have life-altering pain and still request treatment,
      therapy may consist of a well-fitting bra, a decrease in dietary fat intake, and
      discontinuance of oral contraceptives or hormone replacement therapy. Those women
      still resistant to therapy may experience relief from evening primrose oil
      supplements, bromocriptine, tamoxifen, or GnRH analogues. Predicting which
      treatment will be most useful for any particular woman may be challenging. No
      differences in success rates were found to be associated with factors such as
      reproductive history, presenting complaint, personal or family history of breast
      disease, or subsequent need for breast surgery. The peak (but not basal) serum
      prolactin levels in response to thyrotropin releasing hormone stimulus has been
      predictive of success for hormonal treatment but is relatively invasive. A survey
      of treatments actually used was obtained from 276 consultant surgeons in Britain
      in 1990. Of those, 75% prescribed danazol. Others used analgesia (21%), diuretics
      (18%), local excision (18%), bromocriptine (15%), evening primrose oil (13%),
      tamoxifen (9%), a well-fitting bra (3%), and no treatment (10%). Breast
      specialists were more likely to begin treatment with primrose oil, tamoxifen,
      vitamin B6, and analgesia, reserving other hormonal therapies for more difficult
      cases. To further evaluate the women who have severe mastalgia but do not
      complete treatment regimens, a questionnaire was sent to 79 patients who failed
      to return to the Longmore Breast Unit of Western General Hospital, Edinburgh.
      Seventy-one women responded. Of these, 36 said they felt better, 19 said they
      felt no more could be done, 18 learned to live with it, 14 were not worried even
      if the pain recurred, 2 were pregnant, 10 were postmenopausal, and 5 were still
      taking the medications previously prescribed. The prognosis for women with breast
      pain is not always predictable. Women with cyclic breast pain often are relieved
      by events that alter their hormonal milieu, whereas noncyclic breast pain may
      last only 1 to 2 years. Sitruk-Ware and colleagues conducted a study of French
      women with fibroadenomas. They found an association between fibroadenomas and
      cyclic mastalgia occurring more than 1 year prior to the first full-term
      pregnancy. A retrospective, case-control study to determine if cyclic mastalgia
      was a risk factor for breast cancer was conducted on 210 newly diagnosed women
      with breast cancer.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7816408
TI  - Special problems. Mondor's disease, macrocysts, trauma, squamous metaplasia,
      miscellaneous disorders of the nipple.
AB  - This article is a brief synopsis of some rare benign conditions of the breast.
      These conditions include Mondor's disease, macrocysts, trauma to the breast,
      squamous cell metaplasia, and miscellaneous disorders of the nipple. Having some
      knowledge of these conditions will facilitate prompt therapy and avoid
      misdiagnosing malignant breast conditions.

PMID- 7816409
TI  - Benign tumors of the breast.
AB  - Most patients who consult their physician for "breast lesions" do not have a
      malignancy of the breast. The benign lesions of the breast include fibrocystic
      condition, macrocyst fibroadenomas, and intraductal papillomas. Nipple discharge
      is a common condition, and the diagnosis and treatment is discussed. Rarer benign
      tumors such as adenoid tumors, lipomas, neurofibromatosis, benign fibrous
      histiocytoma, and glandular cell tumors are briefly discussed.

PMID- 7816410
TI  - The diagnostic evaluation.
AB  - Breast symptoms are appropriately evaluated by a breast-oriented history and by
      the diagnostic triad of clinical breast examination, FNA, and mammography. In the
      case of a palpable dominant mass, concordance of the diagnostic triad yields a
      reliable clinical diagnosis. If there is not concordance, or if there is any
      doubt about the diagnosis either on the part of the physician or the patient,
      open surgical biopsy provides the definitive histologic diagnosis. The goal in
      clinical practice is to detect nonpalpable cancers by ordering screening
      mammography for all patients eligible by age, history, or both. The long-term
      cancer-free survival of women treated for nonpalpable breast cancer is excellent.

PMID- 7816411
TI  - Benign circumscribed breast masses. Mammographic and sonographic appearance.
AB  - Mammography is an excellent screening tool for the detection of breast masses.
      One of the goals of the radiologist is to separate benign breast masses
      warranting no intervention from the indeterminate and malignant masses that
      require histologic evaluation. Thorough mammographic and sonographic work-up of
      lesions detected at screening will reduce the number of biopsies performed and
      increase the true positive biopsy rate. By systematically evaluating a breast
      mass as to its density location, size, margins, and interval change, one can
      separate benign lesions from those requiring additional work-up and those that
      will require a biopsy diagnosis. Any features suggesting malignancy should prompt
      histologic assessment. For many women, FNAB or large-core needle biopsy, guided
      either stereotactically or sonographically, will not only reduce the morbidity
      associated with excisional biopsy but also decrease the cost of evaluating
      questionable lesions found at screening. Ultrasound examination will further
      reduce the number of biopsies by separating cysts from solid and indeterminate
      lesions that require further evaluation. What rate of carcinoma in biopsy
      specimens should be the mammographer's guideline? Ciatto et al found in his
      series a 30% positive predictive value for mammography in detecting carcinoma. In
      the author's opinion, a goal to strive for should be in the range of 40%. The
      mammographer's experience and confidence as well as patient's compliance with
      follow-up recommendations will help the mammographer reach this goal.

PMID- 7816412
TI  - Reduction and augmentation mammoplasty.
AB  - Women seek reduction mammoplasty for alleviation of their symptoms of mammary
      hypertrophy, which may include upper back and neck pain, strain, or muscle spasm.
      Many of these women also desire an improvement in their appearance. Augmentation
      mammoplasty is sought by women for enlargement of the breasts and to attain a
      well-proportioned figure. Women who have experienced postpartum involution of the
      breasts request augmentation mammoplasty to regain the size and shape of their
      breasts prior to pregnancy. The historical background of these procedures,
      preoperative evaluation, and technical considerations are presented.

PMID- 7816413
TI  - Echographic diagnosis of Drusen of the optic nerve head in patients with angioid
      streaks.
AB  - A total of 58 patients (116 eyes) with angioid streaks, referred to this
      department over 2 years (1990-1992), underwent a thorough ophthalmic examination,
      retinal fluorescein angiography, dermatological visit with skin biopsy, and a
      series of other examinations (blood and biochemistry, skull X-ray, vascular echo
      Doppler, abdominal ultrasound) and eye ultrasonography. Fifty patients (100 eyes,
      86.2%) had pseudoxanthoma elasticum (PXE). In the whole caselist, 21.6% had
      drusen compared with 21.0% in the group with PXE. Both these findings are higher
      than those published elsewhere. Drusen of the optic nerve head were also found in
      25% of the 16 eyes (8 patients) with angioid streaks but no PXE. We believe we
      found a higher prevalence of drusen of the optic nerve head in these patients
      with angioid streaks because we systematically employed ultrasound.

PMID- 7816414
TI  - Mydriatic effect of ocular decongestants studied by pupillography.
AB  - The mydriatic effect of three ocular decongestants, containing 0.1%
      tetrahydrozoline hydrochloride, 0.3% chlorpheniramine maleate, and 0.05%
      tetrahydrozoline hydrochloride in combination with 0.3% pheniramine maleate,
      respectively, was evaluated in 10 healthy volunteers. The study was carried out
      using a single dose of the tested drug, instilling 2 drops in one eye and 2 drops
      of a placebo in the other. The papillary diameters were measured by photographic
      pupillography under basal conditions and 15, 30, 45, 60, 90, and 120 min after
      each treatment. Near and distance visual acuity and tonometry were evaluated
      under basal conditions and 50 and 95 min after instillation of drugs. No
      statistical significant differences between the treated and the control pupil
      diameters were found after instillation of 0.1% tetrahydrozoline hydrochloride or
      0.3% chlorpheniramine maleate. The combination of 0.05% tetrahydrozoline
      hydrochloride with 0.3% pheniramine maleate caused a significant mydriasis from
      30 min up to 120 min (p < 0.01 and p < 0.0005) after instillation, more
      pronounced in light irides. No local and systemic effects and no effects on
      visual acuity and ocular pressure were detected. On the basis of our results, it
      is possible to conclude that the persistent mydriatric action of the two-drug
      combination is due to a synergism; the use of these eyedrops should be avoided in
      subjects with narrow-angle glaucoma, light irides, narrow iridocorneal angle, and
      low anterior chamber for the risk of ocular pressure increase.

PMID- 7816415
TI  - Effectiveness of intraoperative mitomycin C in the treatment of recurrent
      pterygium.
AB  - The effectiveness of intraoperative administration of mitomycin C and the
      occurrence of postoperative complications have been evaluated in 30 white
      patients with one recurrence of pterygium. The authors employed the 'bare-sclera
      technique' and, intraoperatively, placed in the episcleral space for 3 min a
      sterile sponge soaked in a 4% mitomycin C solution. The control group (30
      patients with one recurrent pterygium) underwent only surgical excision.
      Statistical analysis performed using the chi-square test showed a significant (p
      = 0.024) reduction of recurrences of pterygium in the group treated
      intraoperatively with mitomycin C. No heavy side effects occurred during the
      follow-up period. Mitomycin C, administered intraoperatively, may be considered
      an effective treatment to improve the success rate after surgical excision.

PMID- 7816416
TI  - Vector analysis of corneal astigmatism after scleral buckling surgery.
AB  - We conducted a short-term prospective study of 125 eyes with retinal detachment
      to examine changes of corneal astigmatism about 2 weeks after scleral buckling
      surgery, using a vector method on 2-fold-angle rectangular coordinates. Segmental
      buckles of one to less than two quadrants produced significantly greater changes
      in astigmatism (1.65 +/- 0.97 dptr) than those of less than one quadrant (0.88 +/
      0.75 dptr) and those spanning two quadrants or more (1.09 +/- 0.38 dptr) (p =
      0.0005, Kruskal-wallis test; n = 73). The amplitude of differential vectors after
      explant buckling surgery (1.33 +/- 0.89 dptr, n = 24) was significantly greater
      than after implant buckling surgery (0.65 +/- 0.45 dptr, n = 15) (p = 0.009, Mann
      Whitney U-test) with buckles of one quadrant or less. Differential vectors tended
      to direct toward the buckles. There was no obvious directional tendency in the
      case of encircling procedures (n = 52).

PMID- 7816417
TI  - Reduction of intraocular pressure after phacoemulsification and aspiration with
      intraocular lens implantation.
AB  - We prospectively evaluated the pre- and postoperative intraocular pressures (IOP)
      of 1,118 cataract patients. All surgical procedures were performed by the same
      skilled surgeon using the same method of phacoemulsification and aspiration with
      intraocular lens implantation. The mean +/- SE preoperative IOP was 13.29 +/-
      0.12 mm Hg, while the mean IOP values were 10.87 +/- 0.12, 9.94 +/- 0.09, and
      10.43 +/- 0.14 mm Hg 1, 3, and 6 months, respectively, after surgery. When the
      preoperative IOP was in the low 20 s, a decrease of approximately 40% was
      achieved. The present study shows that the IOP decreased postoperatively to a
      greater extent than previously considered, and the rate of decrease was dependent
      on the initial measurement.

PMID- 7816418
TI  - Prospective, randomized, placebo-controlled, double-blind testing of colour
      vision and electroretinogram at therapeutic and subtherapeutic digitoxin serum
      levels.
AB  - In a prospective, randomized, double-blind study with 10 healthy probands,
      changes in colour discrimination and in the pattern electroretinogram (P-ERG) and
      visually evoked cortical potentials (P-VECP) were monitored at therapeutic and
      subtherapeutic digitoxin serum levels. There was a slight increase in the total
      error score in the Farnsworth-Munsell 100-hue test at 0.1 mg digitoxin per day in
      comparison with the placebo. P-ERG and P-VECP did not show any significant
      changes.

PMID- 7816419
TI  - Cefmenoxime in corneal organ culture.
AB  - Before introducing new antibiotics for corneal organ culture solutions,
      information about the endothelial cell toxicity is necessary. Therefore, we
      preserved 132 pig corneas in minimum essential medium with 2% fetal calf serum
      and 5% dextran T 500 and added 50, 100, 250 and 500 micrograms/cm3 cefmenoxime.
      Slight endothelial cell damage occurred at a concentration of 100 micrograms/cm3.
      Damage to endothelial cells was demonstrated by the inhibited uptake of
      fluorescein diacetate and by other staining procedures. 30% of the substance
      remained stable during a 10-day culture period as demonstrated by an HPLC method.

PMID- 7816420
TI  - Immunohistological studies of an oncocytoma.
AB  - An oncocytoma of the upper eyelid that occurred in an 82-year-old male was
      studied immunohistologically according to the avidin-biotin-peroxidase complex
      method (secretory component, carbohydrate antigen 19-9, carcinoembryonic antigen,
      anticytokeratin AE1/AE3, S-100 protein, myoglobin, actin, vimentin). The staining
      properties of columnar-type oncocytes were the same as those of epithelial cells
      of excretory ducts of Moll's gland, but those of polygonal-type oncocytes were
      similar to those of myoepithelial cells of Moll's gland. Our results suggested
      that excretory duct epithelial cells of Moll's gland are the origin of oncocytoma
      of the eyelid.

PMID- 7816421
TI  - Ultrastructural findings and SOD levels in experimental optic nerve injury:
      effect of thyroid-releasing hormone on the degenerative and regenerative
      processes.
AB  - We performed pressure on the left optic nerves of 24 pigs and injected
      intravenous thyroid-releasing hormone (TRH) to 12 of these pigs in order to
      evaluate the degeneration and regeneration in the optic nerves. The
      histopathologic, ultrastructural and biochemical examinations of the optic nerves
      were made at the 24th hour, 7th, 15th and 30th days. Although the light
      microscopic examinations were normal, ultrastructural changes of the uncompressed
      optic nerves were interesting. Histopathologic and ultrastructural investigation
      of the compressed optic nerves showed significant degenerative changes in the non
      TRH-applied group. Ultrastructural comparison yielded lighter degenerative
      changes in the TRH-applied group but there was no clue showing the stimulation of
      regeneration. We observed increased superoxide dismutase (SOD) levels in the
      nontraumatized optic nerves due to the cellular stress. The SOD values were found
      to be low in highly damaged left compressed optic nerves indicating the
      prevention of SOD enzyme synthesis.

PMID- 7816423
TI  - Transconjunctival and transantral approaches are combined with antral wall bone
      graft to repair orbital floor blow-out fractures.
AB  - Orbital floor blow-out fractures in two patients were surgically repaired. The
      transconjunctival approach alone was unsuccessful in freeing the entrapped
      orbital contents, so the transantral approach with the use of antral wall bone
      graft was also used. The combined approaches produced good results. The
      transconjunctival approach supplemented with the transantral approach and bone
      graft may be a useful technique in the repair of orbital floor blow-out
      fractures.

PMID- 7816422
TI  - Effects of antiglaucoma agents on glycosaminoglycans in organ-cultured rabbit
      trabecular meshwork.
AB  - The effect of antiglaucoma drugs on glycosaminoglycans (GAGs) of the rabbit
      trabecular meshwork (TM) was studied by organ culture and sequential enzymatic
      degradation (SED). Whole TM explants from one rabbit eye were dissected into 8
      parts, then divided into control, epinephrine-, timolol- and pilocarpine-treated
      groups. After 2 weeks of culture, and incubation with medium containing
      radiolabeled precursors for 48 h, GAGs of the TM were isolated and subjected to
      SED. Treatment with epinephrine significantly reduced the hyaluronic acid and
      increased the chondroitin sulfate in radiolabeled precursor incorporation rate (p
      < 0.001). Other drugs had little effect. Thus, epinephrine appeared to influence
      the biosynthesis of GAGs of rabbit TM.

PMID- 7816424
TI  - Blink-induced variations in visual performance with toric soft contact lenses.
AB  - BACKGROUND: Blink-induced lens movement causes a reduction in visual performance
      that is potentially greater with toric than with spherical soft contact lenses
      because of the combination of vertical lens movement and rotation. This study
      examined the effect of the two most common methods of toric lens stabilization
      (prism ballast and dynamic stabilization) on vision. METHOD: Four toric soft
      contact lens wearers were the subjects (astigmatic range 1.25 to 2.25 D).
      Stimulus presentation (10.5 cpd sine wave grafting flashed for 16 ms) occurred at
      specified times up to 400 ms after the blink. Contrast thresholds were determined
      monocularly with spectacles and the two types of contact lenses. RESULTS: For the
      grouped data, the prism balasted lens gave better overall visual performance than
      the dynamic stabilization at all times after the blink. Separate analysis of
      subject data suggested that this general pattern was not true for all
      individuals. CONCLUSIONS: Clinical evaluation of different lens designs on
      individual patients is required for achieving the optimum visual performance with
      toric soft lenses.

PMID- 7816425
TI  - Accommodation toward diameter change of a spotlight in a dark room.
AB  - The three-dimensional optometer (TDO III) was used to measure accommodative
      responses when gazing at a spotlight that changed its diameter in an otherwise
      completely dark room. Three emmetropic females served as subjects and the stimuli
      were presented at 33 cm (-3 D) from the subjects. The subjects felt that the
      spotlight approached them when its diameter increased. However, the magnitude of
      accommodation when viewing the smaller diameter spotlight was greater than that
      for the larger diameter spotlight. This means that the eye accommodated less,
      although the spotlight was felt to be nearer, and contradicts the common belief
      based on the subjectively measured data reported earlier. By conducting several
      supplemental experiments, we infer that this phenomenon comes from the effort in
      reducing accommodation lag dynamically in order to see the smaller target more
      clearly.

PMID- 7816426
TI  - Visual changes in human immuno-deficiency virus infection.
AB  - BACKGROUND: Many Human Immuno-Deficiency Virus (HIV) patients develop ocular
      involvement during the course of the disease, including HIV retinopathy and
      cytomegalovirus (CMV) retinitis. It is well established that contrast sensitivity
      and color vision may be affected in other retinal diseases, such as diabetes,
      before obvious signs and symptoms. We therefore examined patients with early HIV
      disease for visual involvement. METHODS: Subjects consisted of 19 HIV-positive
      patients and 15 controls. None of the HIV-positive patients showed any signs of
      HIV retinopathy. High and low contrast visual acuity, luminance contrast
      sensitivity (CS), short wavelength cone (S-cone) CS, and color vision were
      assessed in the right eye of each subject. RESULTS: S-cone CS was significantly
      reduced in the HIV-positive group (HIV mean = 0.91 +/- 0.15 log CS; normal mean =
      1.10 +/- 0.09 log CS, t = 4.19, p < 0.001). Consistent with this finding, four of
      the HIV-positive patients demonstrated tritanopic D-15 results. High and low
      contrast visual acuity and CS were not significantly different in the HIV
      positive and control groups. CONCLUSION: These findings indicate that HIV
      positive patients can have S-cone/tritanopic abnormalities despite normal
      appearing fundi and that there may be damage to the visual system early in HIV
      infection.

PMID- 7816427
TI  - Acute effects of chlorobutanol- or benzalkonium chloride-containing artificial
      tears on the surface features of rabbit corneal epithelial cells.
AB  - I examined the epithelial surface, by high resolution scanning electron
      microscopy, after its recovery from the instillation of artificial tears
      containing chlorobutanol or benzalkonium chloride. Is the mild epithelial surface
      compromise observed after occasional use of a chlorobutanol-containing artificial
      tear more substantial after use of a benzalkonium-containing artificial tear? Two
      drops of a chlorobutanol- or benzalkonium chloride-containing artificial tear
      were instilled into the right eye of 6 female gray rabbits (2 kg) at 9:00 p.m.
      and 9:00 a.m. At the same time six control animals received no eyedrops. All
      animals were euthanized at 3:00 p.m. and the central region of the corneal
      epithelium quantitatively assessed using a digitizer pad/computer system. There
      were up to 5% exfoliating cells evident at the ocular surface in treated rabbits
      but with no difference between the two products. Controls had no cell exfoliation
      (< 0.5%). The distribution of surface areas of the squamous cells in the treated
      eyes was shifted to slightly larger values than in the controls after use of the
      chlorobutanol-containing product but the number of epithelial cell craters/cell
      was unchanged from that of the controls. Cell surface areas were shifted to
      significantly smaller values than controls after use of the benzalkonium chloride
      containing product and there were much fewer epithelial cell craters/cell. The
      results reveal differences in the effects of preservative-containing artificial
      tears on the squamous cells of the corneal epithelium in a clinically relevant
      situation.

PMID- 7816429
TI  - Age and the van Herick ratio in a Chinese population.
AB  - We derived estimates of the van Herick ratio or grading in a retrospective study
      using a Chinese clinical population. We found that the van Herick ratio decreased
      with age and increased with higher degrees of myopia. A lower van Herick ratio
      was found to be associated with higher intraocular pressure. There are
      significantly more patients with lower van Herick ratios or grades in our
      population than in populations described by others.

PMID- 7816428
TI  - Role of the axial length/corneal radius ratio in determining the refractive state
      of the eye.
AB  - The purpose of our study was to investigate the extent to which the ratio between
      axial length and corneal radius (the AL/CR ratio) determines the refractive state
      of the human eye. Subjects for the study were 194 young adults between the ages
      of 18 and 30 years, whose spherical equivalent refraction ranged from +7.91 to 
      13.32 D. For each subject, manifest objective refraction, corneal radii, and
      axial ocular distances were measured. Lens power was determined using a formula
      proposed by Bennett and Rabbetts. The AL/CR ratio was found to be approximately
      3.00 for emmetropic eyes, ranging from 2.60 for the most highly hyperopic eye to
      4.10 for the most highly myopic eye. The coefficient of determination of linear
      regression for the AL/CR ratio as a function of spherical equivalent refraction
      was 0.84, suggesting that 84% of the variance in refraction could be accounted
      for by variance of the AL/CR ratio. The results of the study suggest that for a
      given amount of ametropia, an eye having a relatively high AL/CR ratio would tend
      to have a low-powered lens (indicating that the lens had "emmetropized"), whereas
      an eye having a relatively low AL/CR ratio would tend to have a high-powered
      lens. We conclude that the AL/CR ratio can provide information concerning the
      extent to which the lens has emmetropized by reducing its power concurrent with
      axial elongation.

PMID- 7816430
TI  - Formation of the School of Optometry at the University of Missouri-St. Louis.
AB  - This article traces the formation of the School of Optometry at the University of
      Missouri-St. Louis. The research was conducted by interviewing knowledgeable
      persons, using the archives at The International Library, Archives and Museum of
      Optometry and UM-St. Louis, and using the private papers of Dr. Gordon Heath. The
      review covers three periods from 1968 to 1980: Initial, In-Between, and Final. An
      appropriation for the School was made in each period, but only the last one lead
      to the founding of the School. The political and educational climate of St. Louis
      influenced the development of the School. However, the political activism of
      Missouri optometrists in a receptive state legislature was the main reason for
      the formation of the School.

PMID- 7816431
TI  - Osseointegrated implants in oro-dental and facial prosthetic rehabilitation.
AB  - A basic prerequisite for establishing true and lasting tissue integration of a
      nonbiologic prosthesis is the minimal risk of adverse local or general tissue
      reactions. It consists of a detailed understanding of the response behavior of
      highly differentiated hard and soft tissues to the surgical preparation of a
      recipient site and the installation of the prosthesis, as well as long-term
      tissue adaptation and the functional demands on the anchorage unit. The complex
      arrangement of titanium implant material, surface physics, and biocompatibility
      with the host tissues will be reviewed in this article.

PMID- 7816432
TI  - Polymeric implants in craniomaxillofacial reconstruction.
AB  - With advances in polymer chemistry, polymeric implants are becoming an
      increasingly attractive alternative to autogenous bone. Although polymeric
      implants were traditionally used to bridge bony defects and modify the overlying
      soft tissue envelope, new resorbable polymers may allow bony replacement and may
      be used as alternatives to metals in rigid fixation. This article contains an
      overview of polymeric implants from acrylics to modern resorbable polymers.

PMID- 7816433
TI  - Synthetic bone graft substitutes.
AB  - Some of the most significant advances in biomaterials over the last 20 years have
      been in the field of bone graft substitutes. Additionally, bone growth proteins
      were one of the first tissue-specific morphogenic factors to be characterized and
      produced by recombinant genetic technology. Consequently, the development of a
      new generation of totally synthetic, biologically active bone graft substitutes
      is just now beginning to move from the laboratory to clinical testing. It is
      entirely possible that within the next 10 to 15 years, the majority of "bone
      grafting" in craniofacial reconstructive surgery and in orthopedic surgery may be
      done with biologically active synthetic bone graft substitutes rather than
      natural bone sources. In fact, the harvesting of autogenous grafts may eventually
      prove to be the exception rather than the standard of care. Regardless of whether
      the potential of biologically active bone graft substitutes is ever fully
      realized, we now have a large number of synthetic alternatives to autogenous bone
      grafts for craniofacial skeletal augmentation and reconstruction. The reality of
      these synthetic bone graft substitutes is that no single material is "the best"
      for all applications. Instead, the specific biomaterial must be tailored to the
      individual site of application to achieve optimal results. The synthetic bone
      graft substitutes reviewed in this article represent only the "core" of synthetic
      biomaterials from which synthetic bone graft substitutes can be selected. Other
      articles in this monograph highlight the roles that various natural and
      biologically active bone graft substitutes play in craniofacial skeletal
      augmentation and reconstruction.

PMID- 7816434
TI  - General concepts in craniofacial skeletal augmentation and replacement.
AB  - Craniofacial skeletal reconstruction has reached new levels of sophistication.
      The ability to precisely plan and execute these instructions affords better and
      more predictable outcomes of surgical therapy. This article will focus on the
      general concepts and principles for advanced craniofacial skeletal augmentation
      and replacement.

PMID- 7816435
TI  - Physiology of bone healing and bone grafts.
AB  - Contemporary head and neck hard tissue reconstruction incorporates bone transfers
      in the treatment of osseous discontinuity defects subsequent to congenital
      malformation, traumatic injury, ablative oncologic surgery, and failures of
      physiologic osteosynthesis. Bone grafts may also be applied in contour
      augmentation and in strengthening and stabilization roles in congenital and
      acquired aesthetic as well as posttraumatic deformities. The osseous healing
      process is dynamic and unique. An understanding of the physiology of these
      processes allows the reconstructive surgeon to choose techniques and donor sites
      appropriate to specific requirements, to maximize transplanted bone volume, to
      achieve consistent and reliable results, and to modulate the osseous healing
      process in a favorable direction.

PMID- 7816436
TI  - Surgical planning using three-dimensional imaging and computer modeling.
AB  - The acquisition, processing, and use of three-dimensional (3D) imaging provide
      new insights into normal and abnormal craniofacial anatomy. In this article,
      characteristics of CT and MRI scanning are reviewed along with the methods used
      to delineate tissues and produce 3D patient displays, including contouring,
      shaded surface, and volumetric processing. The use of 3D model fabrication for
      surgical planning is discussed with examples of the production of a custom CT
      based auricle model and the use of rapid prototyping technology to create models
      for custom alloplastic implant surgery. The review concludes with some
      speculation about the future of 3D medical imaging as it will influence surgical
      training and practice over the coming decades.

PMID- 7816437
TI  - Nonvascularized autogenous bone grafts for craniofacial skeletal augmentation and
      replacement.
AB  - Autogenous nonvascularized bone grafts play an important role in the
      reconstruction of complex craniomaxillofacial defects. Experimental animal data
      have demonstrated that grafts from membranous bone donor sites tend to undergo
      less resorption than grafts from endochondral donor sites, probably because of
      the different bony architecture of each of these types of grafts. Of all the
      potential donor sites, the harvest of bone graft from the calvarium is associated
      with the least overall morbidity. Surgeons should be aware of the biologic basis
      for the successful application of free autogenous bone grafts.

PMID- 7816438
TI  - Banked bone.
AB  - Many forms of banked bone allograft are available to the surgeon. Among the
      grafts available are fresh, fresh-frozen, freeze-dried, and demineralized bone.
      Each one of these grafts carries risks and has unique limitations and handling
      properties. In order to use these materials appropriately, the surgeon must be
      familiar with the properties of each and must feel confident that the bone bank
      providing the graft is supplying a safe and sterile graft. In the future,
      allograft bone will become obsolete. In place of banked bone, surgeons will use
      synthetically produced bone morphogenic protein that has been incorporated into
      an absorbable matrix. These materials will exist in a time-release form that will
      allow the graft material to grow and mature with the patient. Until this goal is
      achieved and is available clinically, surgeons must be familiar with the
      capabilities and limitations of banked bone graft.

PMID- 7816439
TI  - Pedicled osseous flaps.
AB  - Craniofacial skeletal defects are most optimally reconstructed with vascularized
      autogenous bone. There are two methods of achieving such a vascularized osseous
      reconstruction: microvascular bone transfers and pedicled osseous flaps. Although
      microvascular composite grafts allow a greater quantity and variety of bone to be
      moved to the reconstructive site, pedicled osseous flaps remain an excellent
      reconstructive option. Pedicled osseous flaps are not technically complex, result
      in minimal donor site morbidity, and demonstrate acceptable reliability in
      selected cases. This article reviews the realm of pedicled osseous flaps that can
      be used in craniofacial reconstruction. Although infrequently employed, these
      useful flaps should remain in the armamentarium of the head and neck surgeon.

PMID- 7816440
TI  - Revascularized bone grafts for craniofacial reconstruction.
AB  - Reconstruction of craniomaxillofacial defects caused by injury, tumor ablation,
      or congenital deformities can be accomplished by a variety of methods.
      Nonvascularized (free), vascularized (pedicled), and revascularized
      (microvascular) bone grafts have been employed for osseous restoration of the
      upper, mid, and lower facial skeleton. In comprised recipient tissue beds or when
      rapid functional restoration is desired, revascularized flaps hold certain
      advantages over their nonrevascularized counterparts. The revascularized flaps
      used most commonly for craniofacial reconstruction are discussed with regard to
      anatomy, clinical applications, and aesthetic and functional limitations.

PMID- 7816441
TI  - Metal plate and screw technology.
AB  - Fundamental to the choice and proper application of plating systems in
      osteosynthesis of the craniomaxillofacial skeleton is an understanding of the
      basic design and biomechanical characteristics that define them. Improper
      selection of systems and technical execution of rigid internal fixation is not
      uncommon and may result in hardware failure, dysfunction, and dysmorphology. The
      surgeon who is able to command the nuances of system design and discipline in
      application will achieve superior functional and aesthetic results that are
      predictable and reproducible.

PMID- 7816442
TI  - Clinical Applications of Vestibular Science. Proceedings of a symposium. Los
      Angeles, California, February 12-13, 1994.

PMID- 7816443
TI  - Studies of inner ear blood flow in animals and human beings.
AB  - This article reviews current studies on inner ear blood flow, discusses their
      relevance to the maintenance of normal homeostasis of the inner ear, reports for
      the first time clear changes in fundamental properties of cochlear blood flow in
      the chronic hydropic ear, and describes the potential of applying laser Doppler
      flowmetry technology to the measurement of inner ear blood flow in human beings.
      Studies of the guinea pig in which perfusion pressure is varied demonstrate a
      broad range of autoregulatory capabilities of the inner ear vasculature. Gain
      factors range from 0.76 and higher for recovery for less than 1 minute of
      modified perfusion pressure. This is significantly greater than reports obtained
      for brain autoregulation. In a series of four investigations of cochlear blood
      flow in the hydropic ear in guinea pigs, a decreased responsiveness to electrical
      stimulation and direct stimulation of the superior cervical ganglia was found,
      indicating a change in sympathetic control of cochlear tone. Reduced vasomotion
      was observed, and autoregulatory capabilities were reduced. In human
      investigations, changes in cochlear blood flow were demonstrated with direct
      electrical stimulation of the round window and warm water irrigation of the ear
      canal, but not with carbogen breathing. Increased cochlear blood flow was
      observed with increased systemic blood pressure, and a remarkable decrease in
      cochlear blood flow was observed with the application of 1:10,000 epinephrine to
      the round window. These observations indicate the potential for development of
      laser Doppler flowmetry technology in the diagnosis and treatment of inner ear
      vascular disorders, and the animal investigations suggest that changes may occur
      in the chronic hydropic ear that compromise autoregulation and thus increase the
      sensitivity of the hydropic ear to other stress factors. Treatments can be found
      to modify such changes in vascular tone.

PMID- 7816444
TI  - Vertebrobasilar insufficiency and stroke.
AB  - Vertigo is the most common symptom of transient ischemia within the
      vertebrobasilar system. Episodes typically come on abruptly and last minutes.
      Although there are usually associated symptoms, isolated attacks of vertigo can
      occur. Vertigo is also a common symptom with brain stem and cerebellar strokes.
      Isolated cerebellar infarction can mimic peripheral vestibular disorders because
      vertigo and imbalance are the main symptoms with both disorders. Modern
      neuroimaging techniques have markedly improved diagnostic capabilities.

PMID- 7816445
TI  - Vascular compression syndrome of the vestibular nerve: a critical analysis.
AB  - The rationale, indications, and surgical results of microvascular decompression
      for the treatment of vertigo are reviewed, and a critical analysis is made. The
      syndrome of disabling positional vertigo is discussed. It is concluded that (1)
      vascular compressive vestibular neuropathy may exist, (2) the current published
      diagnostic criteria for this disorder are insufficient to firmly establish the
      diagnosis, and (3) further work delineating this syndrome should be undertaken.

PMID- 7816446
TI  - Paraneoplastic cerebellar disorders.
AB  - Paraneoplastic cerebellar degeneration typically begins with rapidly progressive
      ataxia of the trunk and extremities. Antineuronal antibodies are found in about
      half the patients. The most specific autoantibody is an anti-Purkinje cell
      antibody found in women with gynecologic tumors. Even after the tumor is removed,
      the cerebellar deficit persists in most patients.

PMID- 7816447
TI  - Metabolic disorders of the vestibular system.
AB  - This article reviews the impact of metabolic disorders on vestibular function.
      Diabetes mellitus is a disorder of glucose metabolism that can be associated with
      vestibular dysfunction. Vertigo can be alleviated by diet management in many
      cases. Elevated levels of blood lipids have been implicated in cochleovestibular
      disorders. Treatment with a lipid-lowering drug has resulted in improved auditory
      and vestibular function in a placebo-controlled trial. Hypothyroidism may affect
      different parts of the vestibular system depending on the severity and duration
      of thyroid deficiency. Severe congenital hypothyroidism can cause central
      vestibular disorders affecting the cerebellum, whereas mild hypothyroidism may
      result in peripheral vestibulopathy. Endogenous alterations in concentrations of
      estrogen and progesterone in the premenstrual syndrome or with the use of
      exogenous hormones such as oral contraceptives may trigger vertigo. Metabolic
      evaluations for unexplained vertigo should include a lipoprotein profile, with
      cholesterol and triglyceride levels, glucose tolerance test, and thyroid hormone
      measurements. Nutritional and drug therapy may be useful to reverse the
      vestibular dysfunction.

PMID- 7816448
TI  - Current perspectives on inner ear toxicity.

PMID- 7816449
TI  - Perilymph fistula pathophysiology.
AB  - A great deal of the controversy associated with perilymph fistula is due to the
      lack of a sensitive, specific way of detecting and thus diagnosing one. The
      existing subjective, clinical observations need to be replaced with an objective,
      scientific methodology having higher specificity and sensitivity for the
      detection of perilymph fistula. Three detection methods presently under
      development are presented here. One uses a miniendoscope to observe the middle
      ear. This procedure is less traumatic than inspection with tympanotomy. Thus it
      is less likely to create artifacts that can be mistaken for a fistula leakage.
      The "yes-no" observation decision is to be replaced with a graded quantitative
      measure. The second method concentrates on detected leakage from inner to middle
      ear. beta 2-Transferrin, a unique endogenous substance found in perilymph and
      cerebrospinal fluid, can be detected with one- or two-dimensional gel
      electrophoresis and immunoblotting. The third method is a system identification
      fistula test. It measures a change in a physiologic response that is caused by
      the presence of the fistula. Classic biophysical models of the vestibular end
      organs can be used to predict the dynamics of responses to systems identification
      stimuli.

PMID- 7816450
TI  - Positional vertigo related to semicircular canalithiasis.
AB  - My clinical and laboratory observations support the theoretical concept that the
      mechanism of typical nystagmus, and most forms of atypical transient nystagmus,
      is hydrodynamic drag by gravitating free densities--most commonly displaced
      otoconia--in the endolymph of a semicircular canal; and that these "canaliths"
      have a significant mechanical advantage, by virture of the canal/ampulla cross
      sectional differential, over densities acting directly on the cupula. Positional
      vertigo related to apparent canalithiasis (benign paroxysmal positional vertigo)
      is a common cause of incapacitation. The profile of the concomitant nystagmus
      localizes the semicircular canal involved. The canalith repositioning procedure,
      appropriately administered and targeted according to the observed nystagmus,
      provides a highly effective means for control of symptoms and a valuable resource
      for diagnostic evaluation of the more complex case. Surgery is rarely indicated.

PMID- 7816451
TI  - Evaluation of vestibular and visual oculomotor function.
AB  - The visual system interacts synergistically with the vestibular system. A
      normally functioning vestibulo-ocular reflex is necessary but not sufficient for
      optimum visual acuity during head motion. Studies of dynamic visual acuity, the
      acuity achieved during relative motion of visual targets or of the observer,
      indicate that motion of images on the retina markedly compromises vision. The
      vestibulo-ocular reflex normally provides a substantial measure of stabilization
      of the retina during head movements, but purely vestibular compensatory eye
      movements are not sufficiently precise for optimal vision under all
      circumstances. Other mechanisms, including visual tracking, motor preprogramming,
      prediction, and mental set, interact synergistically to optimize the gain (eye
      velocity divided by head velocity) of compensatory head movements. All of these
      mechanisms are limited in their capacity to produce effective visual-vestibular
      interaction at higher rotational frequencies and velocities. It is under these
      conditions that vestibular deficits give rise to symptoms of oscillopsia.
      Patients having vestibular lesions exploit mechanisms of visual-vestibular
      interaction to compensate by substitution for deficient vestibular function.
      Thus, for accurate topographic clinical diagnosis of vestibular lesions, testing
      conditions should isolate purely vestibular responses. This may be done by
      testing reflex eye movements during passively generated rotations in darkness, or
      perhaps by testing during other types of motion under conditions of extreme
      frequency and velocity sufficient to attenuate the effects of visual-vestibular
      interaction. This article reviews clinical tests of vestibular function in
      relation to synergistic interactions with vision.

PMID- 7816452
TI  - Vestibular neuritis.
AB  - Because the cause of vestibular neuritis is unknown, this disorder is best
      understood as a constellation of characteristic clinical symptoms and signs. The
      differential diagnosis includes peripheral otologic disorders, including
      Meniere's disease, perilymph fistula, and vestibular atelectasis; and central
      disorders, including vascular insufficiency, acoustic neuroma, migraine
      equivalent, paraneoplastic syndrome, metastatic carcinoma, and multiple
      sclerosis. The site of lesion, as evaluated by clinical signs and symptoms, is
      controversial because concomitant central nervous system abnormalities have been
      described. The histopathology of temporal bones from persons who in life had
      symptoms characteristic of vestibular neuritis demonstrates degeneration of
      branches of the vestibular nerve and the neuroepithelium of vestibular end
      organs. Possible causes of vestibular neuritis include viral or other infectious
      agents and vascular or immune-mediated disorders. The natural history of this
      disorder is variable. In some patients complete recovery of acute signs and
      symptoms, including loss of vestibular response, is seen, whereas in others
      permanent changes have been reported. Initial treatment is generally symptomatic
      only. Patients with poor recovery may benefit from vestibular rehabilitation or,
      occasionally, from surgical intervention. The elucidation of the pathogenesis of
      vestibular neuritis and the development of logical guidelines for individual
      rehabilitation are needed.

PMID- 7816453
TI  - Programmatic vestibular rehabilitation.
AB  - Although the use of vestibular exercises for patients with persistent vertigo and
      dysequilibrium has received some attention for many years, organized vestibular
      rehabilitation therapy programs have only recently been introduced. The benefits
      of such programs are becoming widely accepted. They typically involve a three
      pronged approach: habituation exercises designed to facilitate central nervous
      system compensation by extinguishing pathologic responses to head motion,
      postural control exercises, and general conditioning activities. This article
      will describe the programmatic approach to vestibular rehabilitation, emphasizing
      selection criteria and reviewing results that may be anticipated when this
      treatment modality is used in a variety of patient populations.

PMID- 7816454
TI  - Clinical pathophysiology of vestibular neurectomy.
AB  - This study attempts to characterize the residual vestibular function remaining
      after incomplete supralabyrinthine vestibular neurectomy performed for disabling
      vertigo. Patients with bilateral vestibular neurectomy had preserved horizontal
      vestibulo-ocular reflexes in response to high angular accelerations with gain
      enhancement over time. A torsional down-beating spontaneous nystagmus and an
      important tilt of the subjective vertical were observed when the remaining eighth
      nerve was sectioned after homolateral incomplete supralabyrinthine vestibular
      neurectomy. These findings suggest that a reorganization of vestibular reflexes
      may occur after incomplete supralabyrinthine vestibular neurectomy if afferents
      of the inferior vestibular branch are partially spared. The vestibular function
      after incomplete supralabyrinthine vestibular neurectomy does not affect the
      postoperative control of vertiginous attacks and may have positive effects in
      case of deterioration of the contralateral inner ear.

PMID- 7816455
TI  - Verrucous carcinoma of the larynx.

PMID- 7816456
TI  - Approach to the evaluation of the dizzy patient.
AB  - Dizziness is a nonspecific symptom caused by many different pathophysiologic
      mechanisms. Vertigo, an illusion of movement, indicates a lesion within the
      vestibular system. The duration of attacks and associated symptoms helps to
      determine the site of lesion and likely diagnosis. Examination of the dizzy
      patient should include a careful assessment of gait and balance and a search for
      spontaneous and positional nystagmus. The vestibulo-ocular reflex can be
      evaluated qualitatively at the bedside with the doll's eye, dynamic visual
      acuity, and ice water caloric tests. Each test provides different information
      about vestibular function.

PMID- 7816457
TI  - Imaging of the vestibule.
AB  - PURPOSE: State-of-the-art imaging of the normal and pathologic vestibule. METHODS
      AND MATERIAL: This study is based on the experience of three French imaging
      centers (Val de Grace, Begin, and Saint-Antoine hospitals) working with 1- and
      1.5-tesla magnetic resonance units and high-resolution computed tomography, and
      it includes a review of the literature. Computed tomography is performed with a
      high-resolution program, matrix 512 x 512, field of view 9.6 cm, joined 1-mm
      section, overlapped sections every 0.5 mm, axial and coronal sections, or
      reformatted images. High-resolution magnetic resonance imaging (matrix 512 x
      384), field of view 18 cm, is used with fast T2-weighted sequences (sections 3 or
      2 mm thick, constructive interference in steady state, T2-weighted gradient echo
      sequence three-dimensional Fourier transformation). A joined section of 0.7 mm in
      any direction is obtained if necessary. Superimposition of computed tomography
      and magnetic resonance imaging with a stereotactic technique by identification of
      identical anatomic points is sometimes used. RESULTS: We review the interest and
      place of computed tomography and magnetic resonance imaging in the diseases of
      the labyrinth and internal auditory canal related to abnormal vestibular
      functions: inflammatory labyrinthitis, vestibular hemorrhages, sclerosing and
      ossifying labyrinthitis, traumatism, malformations, perilymphatic fistulas,
      otosclerosis, tumors, cochleovestibular neuritis, and hydrops of the
      endolymphatic system.

PMID- 7816458
TI  - New approaches to the evaluation of the auditory system and a current analysis of
      otoacoustic emissions.
AB  - Healthy ears generate low-level sounds known as otoacoustic emissions that are
      produced by the normal workings of the inner ear. By placing a specially
      constructed probe containing an assembly of miniature microphones in the ear
      canal, hearing investigators can listen to these sounds. Before emissions were
      discovered, the only methods available to explore the ordinarily inaccessible
      structures of the cochlea involved invasive and, thus damaging, experiments,
      which could only be performed on animals. With the discovery of otoacoustic
      emissions, noninvasive research on the inner ear became possible, thus allowing
      study of the fundamental processes that determine the excellent sensitivity and
      fine frequency tuning that are uniquely associated with human hearing. The
      results of these basic experiments have made it possible to develop a number of
      useful clinical applications based on emissions testing. One noteworthy benefit
      is the use of emissions as a screening test that objectively assesses the
      functional integrity of peripheral processing in patients who are difficult to
      examine, such as infants and young children. Other applications take advantage of
      the test's diagnostic strength as an indicator of the sensory component of a
      sensorineural hearing loss. Finally, because emissions testing can be conducted
      rapidly and accurately under computer control, it has proved useful in the serial
      monitoring of ear performance in instances where a progressive hearing impairment
      is suspected.

PMID- 7816460
TI  - Modulation of inner ear pressure in experimental endolymphatic hydrops.
AB  - Physiologic study of the guinea pig model of endolymphatic hydrops has been used
      to better understand the manifestations of Meniere's disease. Quantitative
      vestibular function testing demonstrates some changes in the hydrops subjects,
      especially if an additional stress such as postural inversion is imposed.
      Understanding the hydrodynamic changes on the endolymphatic and perilymphatic
      fluids by the hydrops condition as well as postural inversion may be useful in
      explaining the vestibular findings. These pressure effects may alter the
      micromechanics of the inner ear or possibly induce a relative vascular ischemia.
      Auditory dysfunction is speculated to occur through similar mechanisms.

PMID- 7816459
TI  - Contemporary vestibular function testing: accomplishments and future
      perspectives.
AB  - The development of a standard test battery for the evaluation of vestibular
      function required a variety of preliminary investigations about the technical and
      physiologic foundations of the tests. The most important technologic development
      was the creation of computerized methods, including hardware and software
      capabilities. The designs of tests were based on physiologic and diagnostic
      considerations, as demonstrated in experiments on normal subjects and patients.
      Although time tested and sound, the available test battery satisfies only a
      limited number of requirements for comprehensive evaluation of vestibular
      function. This article describes the list of accomplishments, the state of the
      present limitations, and the needs for the future.

PMID- 7816461
TI  - Role of posturography in the management of vestibular patients.
AB  - Computerized dynamic posturography uses a force platform that can both translate
      and rotate. When combined with visual stimuli, it can be used to determine the
      relative importance of the various sensory inputs critical for balance, namely
      vision, somatosensation, and vestibular sensation. Studies to date have shown
      several patterns of abnormalities on posturography, the best recognized being the
      vestibular pattern. Many patients with a high suspicion of having a peripheral
      vestibular abnormality (based on other information) have such a pattern.
      Moreover, few normal subjects have such abnormalities. Although computerized
      dynamic posturography does not help in localizing a lesion or determining its
      etiology, such testing does provide a functional measure that can be helpful in
      understanding a patient's ability to properly use vestibular system information.
      Posturography is helpful in the management of patients with suspected vestibular
      disorders. In addition to suggesting the presence of a vestibular system
      abnormality, particularly an uncompensated peripheral vestibular deficit, a
      bilateral peripheral vestibular deficit, or a central vestibular abnormality,
      computerized dynamic posturography may help guide the clinician regarding choice
      of treatment and counseling of patients. Further studies are required to
      determine the ultimate role of computerized dynamic posturography in the
      management of patients with vestibular disorders.

PMID- 7816462
TI  - Auditory and vestibular function in experimental hydrops.
AB  - Endolymphatic hydrops is the characteristic morphopathology observed at
      postmortem examination of temporal bones of Meniere's disease. Surgical induction
      of endolymphatic hydrops in the guinea pig provides a reproducible animal model
      for the investigation of some effects of endolymphatic hydrops on inner ear
      function. Episodic and incapacitating vertigo are classic features of Meniere's
      disease, although very limited vestibular dysfunction has ever been described for
      the animal model. On the other hand, the auditory deficits peculiar to Meniere's
      disease, including fluctuant sensitivity losses and a peak audiogram, are also
      observed at different stages in the development of experimental hydrops. In
      future studies the model is likely to provide a means of investigating
      osmoregulatory function of the inner ear.

PMID- 7816463
TI  - Histopathologic findings in Meniere's disease.
AB  - The etiopathogenesis of Meniere's disease has remained controversial since the
      early 1900s. Many investigators have studied the histopathology of the inner ear
      in patients with this disorder. Three basic pathologic mechanisms have emerged:
      fibrosis of the endolymphatic sac and vestibular epithelia, altered glycoprotein
      metabolism, and inner ear viral infection. This article reviews the current
      understanding of these three basic pathologic processes.

PMID- 7816464
TI  - "Tale of a toenail" evokes response.

PMID- 7816465
TI  - Linking up with MEDLINE.
AB  - Pennsylvania physicians are joining the technology bandwagon, accessing medical
      databases from homes and offices equipped with personal computers and telephones.
      This article provides a brief introduction to these electronic libraries,
      focusing on one called MEDLINE. A subsequent article will describe how to gain
      online (telephonic) access to these databases.

PMID- 7816466
TI  - End-of-life decision making and developing international law.
AB  - Physicians may increasingly find themselves enmeshed in the web of controversy
      associated with the propriety of discontinuing treatment, particularly when the
      treatment may provide no discernible therapeutic benefit to an incompetent
      patient. A look at international thinking on this issue offers other
      perspectives.

PMID- 7816467
TI  - Physicians may be vulnerable to silent PPOs.
AB  - The AMA is urging its members to take the lead in eliminating a new insurance
      industry practice which is no only illegal, but is also costing physicians and
      hospitals an enormous amount of money each year.

PMID- 7816468
TI  - Pennsylvania's gubernatorial race: where the candidates stand on health care.

PMID- 7816470
TI  - Telemedicine brings high quality health care to rural Pennsylvania.

PMID- 7816469
TI  - Promoting living wills.

PMID- 7816471
TI  - DUR program moving ahead in second year.

PMID- 7816472
TI  - Preserving values: a dying craft?

PMID- 7816473
TI  - Clinical and cost effectiveness of psychosocial interventions in health care.

PMID- 7816474
TI  - Electronic claims are first step in computerization.

PMID- 7816475
TI  - Controlling diabetes in Pennsylvania. Pennsylvania Department of Health Diabetes
      Control Program.

PMID- 7816476
TI  - Understanding generic substitution.

PMID- 7816477
TI  - Outpatient addiction services expand in Pittsburgh. Interview by Gwendolyn
      Schultz.

PMID- 7816478
TI  - Society venture ever growing.

PMID- 7816479
TI  - Sick care to total care: vertical integration. The Health Care Group.

PMID- 7816480
TI  - The asthma crisis.

PMID- 7816481
TI  - Descartes' physiology of pain.

PMID- 7816482
TI  - Differential behavioral outcomes in the sciatic cryoneurolysis model of
      neuropathic pain in rats.
AB  - We have previously introduced a novel animal model of neuropathic pain in rats
      following a peripheral mononeuropathy produced by freezing the common sciatic
      nerve, a technique termed sciatic cryoneurolysis (SCN). In this study, we have
      further characterized the temporal pattern of behavioral changes following SCN,
      including thermal hyperalgesia and mechanical allodynia. These behaviors were
      assessed using noxious thermal (radiant heat) and non-noxious tactile (von Frey
      filament) stimuli, respectively. Following unilateral SCN, animals exhibited
      significant (P < 0.001) bilateral tactile hypersensitivity (allodynia) that
      persisted at least 10 weeks. However, this lesion did not result in thermal
      hypersensitivity (hyperalgesia). In fact, thermal sensitivity in the operated
      limb remained significantly suppressed throughout the 10 weeks (P < 0.001).
      Furthermore, we observed autotomy in 76% of SCN-lesioned animals as well as
      transient weight loss and pale eye syndrome (PES), a phenomenon previously
      unreported in other neuropathic pain models. PES is a sustained, visibly distinct
      pallor of the normally pink eye color of the albino rat. We believe PES is a
      putative marker of heightened sympathetic efferent activity. The severity of
      autotomy following SCN correlated significantly with both weight loss (P < 0.001)
      and the expression of PES (P < 0.001). Autotomy behavior preceded the onset of
      allodynia; however, there was no correlation between the severity of expression
      of these behaviors. These behavioral sequelae are comparable to those seen in
      other animal models of neuropathic pain, but differ in respect to the increased
      frequency of autotomy and the lack of thermal hyperalgesia.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7816483
TI  - Sensitization of high mechanothreshold superficial dorsal horn and flexor motor
      neurones following chemosensitive primary afferent activation.
AB  - Nociceptive primary afferents have the capacity to induce a state of increased
      excitability or central sensitization in dorsal horn neurones. This contributes
      to the mechanical hypersensitivity (allodynia) which occurs after peripheral
      tissue injury where low-mechanothreshold primary afferent activation begins to
      elicit pain. The relative susceptibility of dorsal horn cells with an apparent
      exclusive nociceptive input (nociceptive-specific (NS) or high-threshold (HT)
      cells) and those with a convergent input from low- and high-threshold
      mechanoreceptors (wide-dynamic-range (WDR) or multireceptive neurones) to
      sensitivity changes has been disputed. We have examined whether high
      mechanothreshold neurones in the superficial dorsal and the ventral horn can
      modify their sensitivity following cutaneous application of the chemical irritant
      mustard oil. This produced both a prolonged reduction in the mechanical threshold
      of the cutaneous flexion withdrawal reflex, recorded from semitendinosus alpha
      motor neurones, and an increase in the activity evoked in these neurones by low
      intensity touch stimuli to the glabrous skin. Eight NS or HT only cells, defined
      in terms of their cutaneous mechanoreceptive field properties, were recorded in
      the superficial dorsal horn before and after cutaneous application of mustard
      oil. Mustard oil was applied outside of the mechanical receptive field of the
      cells and produced a transient increase in action potential discharge in 4 cells
      but increased the mechanoreceptive field size in all cells for 30-60 min.
      Mechanical thresholds declined in 6 cells to levels associated with low-threshold
      (LT) and WDR cells, and this was accompanied by recruitment of a novel
      brush/touch response in 5 cells. The responses evoked by graded electrical
      stimulation of the sural nerve were tested in 5 cells. Only 1 cell failed to show
      any change after mustard oil. In 3 cells, an increase in the response to A-fibre
      afferents occurred, a novel A-fibre response was recruited in 2 cells and the C
      fibre response increased in 2 cells. Cells in the superficial dorsal horn of the
      rat spinal cord that are normally NS can begin, therefore, to respond to LT
      primary afferent mechanoreceptors after an increase in central excitability
      produced by activation of peripheral chemoreceptors. Sensitization of these, as
      well as of WDR cells, may contribute to the generation of post-injury mechanical
      pain and reflex hypersensitivity.

PMID- 7816484
TI  - The resolution of neuropathic hyperalgesia following motor and sensory functional
      recovery in sciatic axonotmetic mononeuropathies.
AB  - Nerve lesions producing extensive axonal loss can induce painful hyperalgesic
      states in man. The affect of axonal regeneration and end-organ reinnervation on
      hyperalgesia and pain is controversial. This study used two axonotmetic models,
      the sciatic crush injury (CI) and the sciatic chronic constrictive injury (CCI),
      to investigate the affects of nerve regeneration and reinnervation on
      hyperalgesia and presumed painful behavior in rats. The sciatic CI resulted in a
      transient loss of both sciatic motor function and the withdrawal response to
      pinch and heat in the sciatic distribution. Extensive recovery of motor function,
      pinch and heat response occurred over days 23-38 post-crush injury. This
      temporally corresponded with a plateau in the hindpaw autotomy score and a
      resolution of the saphenous-mediated pressure and heat hyperalgesia (adjacent
      neuropathic hyperalgesia; ANH) which developed over the medial dorsum of the
      hindpaw following the sciatic CI. In contrast, with sciatic transection and
      distal stump excision, no motor recovery occurs, large areas of the hindpaw
      remain unresponsive to heat and pinch, and the saphenous mediated ANH fails to
      resolve over a period of 3 months. When sciatic CI was compared to contralateral
      sciatic transection within the same rat, the bilateral saphenous-mediated
      pressure and heat thresholds were initially identical, but by 23-27 days post
      crush, the crush side thresholds became hypoalgesic relative to the section side.
      This demonstrates an attenuation of the crush-induced ANH which temporally
      corresponds to the recovery of motor and sensory function. When the sciatic nerve
      was proximally crushed and distally transected (3 cm below the crush site), the
      saphenous-mediated pressure and heat threshold changes were identical (over 6
      weeks of serial testing) to those produced by a contralateral sciatic transection
      within the same rat. This indicates that the microenvironments surrounding the
      regenerating axon tips did not differentially affect the development of ANH
      following sciatic CI or transection. The sciatic CCI resulted in a transient loss
      of hindpaw motor function without the loss of pinch or heat withdrawal responses
      in the sciatic distribution. Motor function recovery occurred primarily over days
      23-59 post-ligature. During this prolonged period of motor function recovery
      there was a resolution of the sciatic-mediated plantar surface heat hyperalgesia
      and the saphenous-mediated heat ANH. The above data support the hypothesis that
      the successful regeneration of distal axons after axonotmetic lesions can
      initiate the resolution of neuropathic hyperalgesia.

PMID- 7816485
TI  - Spinal nociceptive transmission in the spontaneously hypertensive and Wistar
      Kyoto normotensive rat.
AB  - Background and noxious heat-evoked responses of wide-dynamic-range (WDR) and high
      threshold (HT) lumbosacral spinal dorsal horn neurons were recorded in
      spontaneously hypertensive rats (SHRs), Wistar-Kyoto normotensive rats (WKYs),
      lifetime captopril-treated SHRs, SHRs with bilateral cervical vagotomy, SHRs with
      bilateral sino-aortic deafferentation (SAD), and SHRs with either a single or
      repeated administration of naloxone methobromide (NMB). Stimulus-response
      functions (SRFs) were generated for neurons using 15 sec of heating of the foot
      at temperatures ranging from 38 to 52 degrees C. Comparisons were made of
      neuronal response thresholds, slopes of the SRFs, mean discharge frequency during
      heat stimulation, arterial blood pressure (ABP), and heart rate (HR). The primary
      finding was that group mean SRFs for both WDR and HT neurons were shifted in a
      parallel, rightward fashion in SHRs compared to WKYs. Heat-evoked response
      thresholds were increased and asymptotic discharge frequencies were decreased in
      WDR and HT neurons of SHRs compared to WKYs. Analyses of group mean SRFs for WDR
      and HT neurons of SHRs receiving lifetime captopril treatment indicated they were
      normalized to the SRFs of WKYs, but detailed comparisons using discharge
      frequency during heat stimulation revealed that this was due to a statistical
      averaging effect. Specifically, lifetime captopril-treated SHRs not only showed
      enhanced neuronal responses to the onset of noxious heat but also enhanced
      adaptation of neuronal responses with continued heating compared to WKYs.
      Bilateral SAD in SHRs significantly increased the total discharge frequency of
      WDR neurons to heat stimuli between 44 and 52 degrees C, but produced no change
      in the response threshold for heat-evoked activation of these neurons. A similar
      effect of SAD was observed in HT neurons of SHRs, but the greater response
      thresholds of HT neurons precluded detection of any significant effect. Bilateral
      cervical vagotomy did not affect response thresholds, slopes, or total discharge
      frequencies of SHRs, although only WDR neurons were studied. SRFs of WDR and HT
      neurons in SHRs obtained pre- and post-administration of a single dose of NMB did
      not differ. However, repeated administration of NMB in SHRs resulted in a
      parallel, leftward shift in SRFs of both WDR and HT neurons. In all strains and
      treatments studied, there were no significant differences in background
      activities of these neurons that might contribute to the observed outcomes. In
      conclusion, the hypoalgesia reported in human essential hypertensives and animals
      with chronic hypertension may be due to a significant attenuation in spinal
      nociceptive transmission.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7816486
TI  - Altered heat pain thresholds and cerebral event-related potentials following
      painful CO2 laser stimulation in subjects with fibromyalgia syndrome.
AB  - A decrease in mechanical pressure pain thresholds, particularly over pre
      designated tender points, is one of the defining characteristics of fibromyalgia
      syndrome (FS); however, changes in thermal pain sensitivity have not been
      investigated. The present study examined heat pain thresholds and cerebral event
      related potentials following CO2 laser stimulation in 10 subjects with FS and 10
      age-matched control volunteers. The results indicate that patients with FS
      exhibit a significant reduction in heat pain threshold when tested on the dorsal
      surface of the hand. In accordance with previous research, we also found a
      decrease in mechanical pain threshold over pre-designated tender points and at
      control sites as well as a significantly larger mechanically induced neurogenic
      flare response. These measures were highly correlated with thermal pain threshold
      even though different anatomical sites were stimulated. Hence, it seems likely
      that FS patients display a multimodal change in pain sensitivity which is
      generalized rather than anatomically restricted. Patients with FS also displayed
      a significant increase in the peak-to-peak amplitude of the cerebral potential
      evoked by CO2 laser stimulation at pain threshold intensity and 1.5 times pain
      threshold intensity. These findings suggest a greater activation of central
      nervous system (CNS) pathways following noxious input. Putative explanations for
      the increased CNS response are discussed, including mechanisms of peripheral
      nociceptor sensitization, altered CNS function and the role of psychological
      factors.

PMID- 7816487
TI  - The false-positive rate of uncontrolled diagnostic blocks of the lumbar
      zygapophysial joints.
AB  - One hundred and seventy-six consecutive patients with chronic low back pain and
      no history of previous lumbar surgery were studied to determine the false
      positive rate of single diagnostic blocks of the lumbar zygapophysial joints. All
      patients underwent diagnostic blocks using lignocaine. Those patients who
      obtained definite or complete relief from these blocks subsequently underwent
      confirmatory blocks using bupivacaine. Eighty-three patients (47%) had a definite
      or greater response to the initial, lignocaine injection at one or more levels
      but only 26 (15%) had a 50% or greater response to a confirmatory injection of
      0.5% bupivacaine. Using the response to confirmatory blocks as the criterion
      standard, the false-positive rate of uncontrolled diagnostic blocks was 38% and
      the positive predictive value of these blocks was only 31%. Because the positive
      predictive value of a test is lower when the pre-test probability (prevalence) is
      low, and because the prevalence of lumbar zygapophysial joint pain is likely to
      be less than 50%, uncontrolled diagnostic blocks will always be associated with
      an unacceptably low positive predictive value. These features render uncontrolled
      diagnostic blocks unreliable for the diagnosis of lumbar zygapophysial joint pain
      not only in epidemiologic studies but also in any given patient.

PMID- 7816488
TI  - Pain behavior in industrial subacute low back pain. Part I. Reliability:
      concurrent and predictive validity of pain behavior assessments.
AB  - The reproducibility of overt pain behavior ratings was shown to be reliable
      between independent observers. In the clinical evaluation of 103 blue collar
      workers with subacute low back pain (LBP), concurrent validity was high between
      Behavioural Signs (Waddell et al. 1980) and UAB Pain Behavior Rating scale
      (Richards et al. 1982). Correlations with pain rated on visual analogue scales
      (Scott and Huskisson 1976) were generally lower. Behavioural Signs correlated
      separately with covert pain behavior (general convictions concerning back
      strength and general health). It seems that subacute LBP patients do not behave
      as a homogenous group since pain behaviors predicted occupational handicap
      (absenteeism) in a non-linear fashion. Return to work was best predicted by UAB
      and covert pain behavior, absenteeism up to 2 years by covert pain behavior. The
      findings emphasize the potential social implications of overt pain behaviors and
      the importance of covert pain behavior in maintaining the sick role. The
      conclusion is that, in secondary prevention, where the main targets are to
      interfere with somatic deconditioning and sick-role development, a more
      diversified primary approach may be possible, based on supplementary use of
      relatively easy observational tests and quick self-reports.

PMID- 7816489
TI  - Altered tachykinin expression by dorsal root ganglion neurons in a rat model of
      neuropathic pain.
AB  - The experiments described in the present study approached nerve injury from both
      a biochemical and anatomical perspective by monitoring changes in expression of
      preprotachykinin (PPT) mRNA encoding the prototypic tachykinin substance P and
      related peptide species in neurons of the rat dorsal root ganglia (DRG) following
      unilateral chronic constriction injury of the sciatic nerve. In situ
      hybridization histochemistry (ISHH) analyses in conjunction with computer
      assisted image processing were employed to quantify levels of PPT mRNA
      distributed in DRG neurons. Injury-induced changes in PPT mRNA expression by
      affected DRG neurons included: (1) at early postoperative times, generally
      increased levels of PPT mRNA associated with small and intermediate-size B cells
      exhibiting normal morphology, (2) at late postoperative times, markedly decreased
      levels of PPT mRNA associated with degenerating B cells, and (3) induction of PPT
      gene expression by large A cells which is highly correlated with degenerative
      morphological changes. The significant aspects of these changes are discussed
      with special emphasis on the contribution of altered transmitter expression by
      DRG neurons to the pathophysiology of causalgia. In particular, the induction of
      PPT gene expression by many of the large neurons undergoing degenerative changes
      may represent an important biochemical parameter which is associated with the
      development and persistence of experimental allodynia.

PMID- 7816490
TI  - Patient-related barriers to management of cancer pain in Puerto Rico.
AB  - Two hundred and sixty-three ambulatory patients older than 21 years of age who
      were attending clinics at an oncology hospital in San Juan, Puerto Rico, were
      studied. They completed a questionnaire (BQ-PR) that measures 8 concerns about
      reporting pain and using analgesics, such as fears of addiction and tolerance and
      the belief that reporting pain can distract a physician from focusing on curing
      one's disease. Ninety percent of the patients had at least some concern about
      each of the 8 topics, and mean scores on the 8 subscales were near the midpoint
      on a 0-5 scale. There were significant inverse relationships between level of
      education, income, and BQ-PR total score. Those persons who experienced cancer
      related pain on the day they completed the questionnaire were categorized as
      using adequate versus not adequate analgesic medication, a determination that was
      based on a comparison of their level of pain to the medication they were using.
      Those who were not using adequate analgesic medication had higher BQ-PR total
      scores than did those who were using adequate medication.

PMID- 7816491
TI  - Long-term results of cervical epidural steroid injection with and without
      morphine in chronic cervical radicular pain.
AB  - To evaluate the long-term effectiveness of a single cervical epidural steroid
      injection (CESI) performed with or without morphine, 24 patients, without need of
      surgery, but suffering for more than 12 months from cervical radicular pain, were
      included in a prospective and randomised study. The cervical epidural space was
      injected (C7-D1; 18-ga needle) with an increasing volume (10 ml maximum) of
      isotonic saline solution to exacerbate the patient's radicular pain. The patients
      were then randomly allocated to 2 groups: the steroid group (group S, n = 14)
      received an equivalent volume of 0.5% lidocaine plus triamcinolone acetonide (10
      mg/ml) and the steroid plus morphine group (group S + M, n = 10) received the
      same combination plus 2.5 mg of morphine sulphate. Pain relief was assessed as
      the percentage of pain decrease on a visual analogue scale on day 1 and at months
      1, 3, 6, 8 and 12 after CESI, up to 48 months. Anthropometric data between the 2
      groups were similar. The mean volume injected in the epidural space was: 6.6 +/-
      2.1 and 6.3 +/- 1.9 ml in groups S and S + M, respectively, and this volume
      exacerbated pain in 21 of 24 patients. Despite observing a better transient
      improvement the day after CESI in the S + M group, long-term results did not
      differ. The success rate was 78.5% in group S and 80% in group S + M providing
      pain relief of 86.8 +/- 14.7% and 86.9 +/- 17.9%, respectively. Pain relief
      remained stable with time (mean follow-up: 43 +/- 18.1 months).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7816492
TI  - The effects of intrathecal morphine and clonidine on the prevention and reversal
      of spinal cord hyperexcitability following sciatic nerve section in the rat.
AB  - We have previously shown that intrathecal (i.t.) morphine, but not the alpha 2
      adrenoreceptor agonist clonidine, administered prior to sciatic nerve section,
      reduced the level of autotomy in rats, which is a behavioural model of
      neuropathic pain. Neither drug was effective when administered 15 min after nerve
      section. We now examined the effects of i.t. morphine and clonidine on the
      development of flexor reflex hyperexcitability following sciatic nerve section in
      acute physiological experiments. The flexor reflex was recorded from the
      hamstring muscles in decerebrate, spinalized, unanesthetized rats. The effect of
      sciatic nerve section on the flexor reflex without drugs was compared with
      axotomy performed 60 min after i.t. injection of 3 micrograms or 30 micrograms
      morphine, as well as 50 micrograms clonidine. The effect of these drugs on
      reversing reflex hyperexcitability was also examined. Both doses of morphine
      administered prior to sciatic nerve section profoundly depressed the baseline
      reflex and the higher dose almost completely abolished reflex hyperexcitability
      following nerve section. In contrast, clonidine pre-administration was less
      effective in depressing the baseline reflex and blocked reflex hyperexcitability
      less than morphine. Both morphine and clonidine administered 15 min after nerve
      section reversed spinal hyperexcitability. Thus, the ability of morphine to
      prevent the occurrence of autotomy may be related to its effectiveness in
      blocking axotomy-induced hyperexcitability. These physiological data suggest that
      even a short period of spinal cord hyperexcitability following nerve injury may
      lead to the development of neuropathic pain.

PMID- 7816494
TI  - Longitudinal study on the role of personality characteristics and psychological
      distress in neck trouble among working men.
AB  - The role of personality characteristics and psychological distress in the
      occurrence of severe neck trouble was investigated in a 3-year follow-up study
      conducted from 1984 to 1987 among 1015 men (age: 25-49 years old) employed as
      machine operators, carpenters and office workers. The subjects had reported in a
      questionnaire in 1984 that they had experienced no more than 7 days with neck
      trouble during the past 12 months. Based on a similar questionnaire in 1987,
      severe neck trouble was defined as trouble having lasted more than 30 days.
      Psychological distress and personality characteristics were assessed in 1984 by
      the Middlesex Hospital Questionnaire (MHQ) and the Maudsley Personality Inventory
      (MPI) respectively. Severe neck trouble occurred in 11% of the subjects, who were
      considered as cases; those with 0-7 days with neck trouble were considered as
      controls. When individual and occupational factors were adjusted for no powerful
      predictors were found. However, after performing a backward stepping analysis,
      somatic symptoms and hysteria were significantly associated with severe neck
      trouble. In occupation-specific analyses, somatic symptoms and neuroticism were
      significantly associated with the occurrence of severe neck trouble among the
      machine operators, as were somatic symptoms, depression and hysteria among the
      office workers. Neither the personality characteristics nor psychological
      distress predicted the occurrence of severe neck trouble among the carpenters. We
      conclude that the associations between psychological factors and neck trouble are
      complex and may depend on the psychosocial environment.

PMID- 7816493
TI  - Encoding and decoding of pain expressions: a judgement study.
AB  - The communication of pain requires a sufferer to encode and transmit the
      experience and an observer to decode and interpret it. Rosenthal's (1982) model
      of communication was applied to an analysis of the role of facial expression in
      the transmission of pain information. Videotapes of patients with shoulder pain
      undergoing a series of movements of the shoulder were shown to a group of 5
      judges. Observers and patients provided ratings of the patients' pain on the same
      verbal descriptor scales. Analyses addressed relationships among patients' pain
      reports, observers' judgements of patients' pain and measures of patients' facial
      expressions based on the Facial Action Coding System. The results indicated that
      although observers can make coarse distinctions among patients' pain states, they
      (1) are not especially sensitive, and (2) are likely to systematically downgrade
      the intensity of patients' suffering. Moreover, observers appear to make
      insufficient use of information that is available in patients' facial expression.
      Implications of the findings for pain patients and for training of health-care
      workers are discussed as are directions for future research.

PMID- 7816495
TI  - Bipartite piriformis muscle: an unusual cause of sciatic nerve entrapment.
AB  - The sciatic nerve usually emerges below the piriformis muscle; however,
      variations of the relationship between the sciatic nerve and piriformis muscle
      are occasionally encountered. In a 28-year-old woman with sciatica, entrapment of
      the sciatic nerve by a bipartite piriformis muscle was found. She was treated by
      dissection of the lower head of the piriformis muscle and restitution of the
      normal anatomical relationship between the nerve and piriformis muscle. Sciatica
      resolved postoperatively.

PMID- 7816496
TI  - Hyaluronidase in the management of pain due to post-laminectomy scar tissue.
AB  - We describe a 31-year-old male with a rebound radicular syndrome due to post
      laminectomy scarring in the intervertebral foramen and epidural space. Repeated
      injection of hyaluronidase through the intervertebral foramen into the scar
      tissue resulted in periods of appreciably reduced pain and increasing duration.
      No untoward effects were seen.

PMID- 7816497
TI  - 'Mirror pain' and indications of bilateral dorsal horn activation in response to
      unilateral nociception.

PMID- 7816498
TI  - Comments on A. Ekblom and P. Hansson.

PMID- 7816499
TI  - Are all those pain ratings necessary?

PMID- 7816500
TI  - Comments on psychosocial factors in chronic spinal cord injury pain by Summers,
      Rapoff, Varghese, Porter, and Palmer.

PMID- 7816501
TI  - [The specificity of blastocysts (Rhizopoda: Lobosea)].
AB  - The analysis of specificity of blastocysts was based on the data on host
      association and on experimental data. In experiments we failed to infect the
      geese (Anser anser) with Blastocystis galli taken from the fowl (Gallus gallus)
      and also failed to infect the fowl with B. suis taken from the pigs (Sus scrofa
      domestica). Experimental data and field observations of blastocysts distribution
      among different groups of hosts point out that the same species of blastocysts
      can not parasitize in hosts belonging to different classes and orders. The
      examination of 89 fish specimens belonging to 14 species of Osteichthyes taken
      from the Neman delta did not discover any blastocysts.

PMID- 7816502
TI  - [The absolute count of the housefly (Musca domestica) and the stable fly
      (Stomoxys calcitrans) in buildings for cattle].
AB  - The direct correlative dependence between indices of absolute and relative number
      of two fly species calculated by Peterson's method is shown. The way of
      calculation of the absolute number of M. domestica and S. calcitrans and the
      receipt of the selection from subpopulations, which take in account peculiarities
      of adult fly distribution in different technological regimes of cattle keeping,
      peculiarities of daily activity and influence of temperature-photo factors on
      imago, are proposed. The attempt to study the structure and density of
      subpopulation of two fly species during one generation in North-West Russia is
      made. The date on mortality on different stage of life cycle are given.

PMID- 7816503
TI  - [The T-cell response in parasitization by sheep bot (Oestrus ovis) larvae].
AB  - The kinetics of immunocompetent cells in sheep artificially infested with 80,
      160, 1000 specimens of Oestrus ovis larvae and immunized with antigen from larvae
      protein was traced by stableons (E-REC) and antigen-fixing (Ag-REC) rosette
      formation reaction. It was found that E-REC level changes only a little in both
      infested and reinfested animals. Ag-REC kinetics mates with the rated larvae
      biomass changes in all age groups. Ag-REC level of infested animals is much
      higher and then regularly declines in the following cycles of invasion. T
      lymphocytes level and death level of immunized lambs is much higher than in
      intact animals at the beginning of parasitism.

PMID- 7816504
TI  - [A comparative electrophoretic analysis of the isoenzymes in "reference" and
      natural strains of Trichinella].
AB  - In four enzymes among eight ones examined the differences were revealed in the
      intensity of staining of certain zones (G-6-P, ES) as well as in electrophoretic
      mobility of some loci (PGD, RGM) between the capsule forms of trichinellae and
      Trichinella pseudospiralis. As a result, the validity of isolation of T.
      pseudospiralis Garkavi, 1972 is confirmed.

PMID- 7816505
TI  - [New species of didymozoates (Trematoda) from the Atlantic mackerel tuna].

PMID- 7816506
TI  - [Microsomacanthus paraparvula sp. n. (Cestoda: Hymenolepididae)--a parasite of
      diving ducks in Chukotka].
AB  - Microsomacanthus paraparvula sp. n. differs from all other species of the genus
      by extremely small length of proglottids and genital organs. The size and general
      shape of the hooks closely resemble those of M. parvula (Kowalewski, 1904).
      However, the new species performs twice as many proglottids for the same specimen
      size. The dimensions and topography of the internal organs are also different,
      the cirrus sac size being one third of that in M. parvula. Finally, the new
      species represents a distinctly different life cycle using the caddisfly as the
      intermediate host.

PMID- 7816507
TI  - [The life cycle of Mosesia longicirrus sp. n. (Trematoda: Lecithodendriidae) in
      the south of the Russian Far East].
AB  - The life cycle of the trematode Mosesia longicurrus was examined in experimental
      conditions. It is established, that the parasite develops in two intermediate
      hosts, the first hosts are snails of the genus Juga, the second ones are
      different species of Ephemeroptera and Plecoptera, the final hosts are birds.

PMID- 7816508
TI  - [The classification of the morphological forms of flagellates in the family
      Trypanosomatidae].
AB  - The partial revision of the generally accepted classification of the
      morphological forms of trypanosomatid flagellates (Hoare, Wallace, 1966) is
      proposed. Only "flagellar" characteristics without evaluation of the form of the
      body and systematic position of the flagellates are used in the new variant of
      the classification. Six basic morphological forms of trypanosomatids have been
      included in proposed scheme: amastigotes, endomastigotes, promastigotes,
      opisthomastigotes, epimastigotes, trypomastigotes.

PMID- 7816509
TI  - [Diphyllobothrium lobodoni sp. n. (Cestoda: Diphyllobothriidae)--a parasite of
      the crabeater seal].
AB  - The new cestode species is described from the intestine of the crab eater seal
      Lobodon carcinophagus living in Pacific region of Antarctic. It differs from
      other diphyllobothriids by clear wavy lateral margins of the body. It is close to
      D. scoticum by the presence of uterine sack, but it has larger size of the body,
      lesser craspedotity of segments, lesser size of scolex, longer neck, thinner
      tegument, 3 times thicker layers of longitudinal and transversal muscles, 2 times
      greater number of testicles (per transversal section of the segments), another
      form and position of the bursa of cirrus and of the testicular vesicle, larger
      uterine sack consisting about one third of the total uterine volume.

PMID- 7816510
TI  - [Iso-osmotic regulation in cestodes from freshwater fishes].
AB  - The content of sodium, potassium, calcium, and magnesium ions was determined in
      cestodes Ligula intestinalis, Eubothrium rugosum, and Triaenophorus nodulosus. In
      freshwater fishes the total concentration of Na, K, Ca, Mg ions in cestode tissue
      water is practically similar to that of fishes muscles and in serum. It was
      suggested that examined cestodes have isoosmotic regulation of the water-salt
      balance.

PMID- 7816512
TI  - [Methods for studying the distribution of Monogenea in the gills of fishes].
AB  - The infection rate with monogeneans of different sites of fish gills was
      examined. The comparative analysis of average parts (in %) was made after [see
      text] Fisher where phi is a percentage in radians, n -- the number of fishes
      dissected, v -- degrees of freedom. It was shown statistically, that part (%) of
      dactylogyrids on II paris of the gills is significantly greater than parts from I
      and III pairs of the gills. The parts of the parasites were not distinguished on
      I and III pairs of the gills. The part of worms on IV pair of the gills is the
      least. It was shown that statistically significant part of the dactylogyrids was
      observed in the middle sector of the gills. Factors, which could led to unequal
      distribution of monogeneans on the gills, are discussed. The main factor appears
      to be a volume of water stream passing through different pairs of the gills.

PMID- 7816511
TI  - [The host-opportunistic protozoa system. The dissemination of Leishmania infantum
      infection in naturally susceptible laboratory animals subjected to drug-induced
      immunosuppression].
AB  - The possibility to awake the disseminated infection of Leishmania infantum in
      golden hamsters Mesocricetus auratus, hispid cotton rats Sigmodon hispidus, soft
      furred rats Mastomys natalensis by means of different immunodepressants has been
      examined. On the background of the immunosuppression caused by corticosteroids of
      short time activity (metipred, hydrocortison) leishmaniae were revealed both in
      the target organs (spleen, liver, marrow) and in lungs, in cases of using the
      corticosteroid of prolonged activity (tricort-40) leishmaniae were observed also
      in lungs, kidneys, testis.

PMID- 7816513
TI  - [The siphonal index of Culex pipiens mosquito larvae (Diptera: Culicidae) from
      Russia and adjacent countries: its variability and use for the diagnosis of
      forms].
AB  - In 70 natural populations and laboratory strains of Culex pipiens from the former
      Soviet Union (32 settlements, 37-62 N, 38-93 degrees E) the larval siphonal index
      was studied, in 29 populations the adult biological peculiarities (the autogeny,
      the stenogramy and the bloodsucking activity on the human) were studied also in
      the laboratory. The individual siphonal index varies considerably from 2.2 to 7.9
      and has the normal distribution shape. The mean index is correlated with the
      larval biotope (open or underground reservoirs) and with biological
      peculiarities. In autogenous and stenogamous populations the mean siphonal index
      varies from 3.7 to 4.6 (average 4.1), in nonautogenous and eurigamous ones--from
      4.7 to 5.6 (average 5.1). The biological mechanisms which provide the
      differentiation and isolation of the forms C. p. pipiens and C. p. molestus in
      the temperate zone are discussed. These mechanisms include the capacity to
      diapause, the ability to copulate in the restricted space (stenogamy), and the
      biotopic specialization of the larvae (open or underground reservoirs). The
      individual variation of siphonal index is often too high, therefore the
      identification of the individual larvae is unreliable. However, the mean siphonal
      index of the population can be recommended for the identification of the forms in
      populations from the temperate latitudes: in C. p. molestus the mean siphonal
      index is 4.3 and lower, in C. p. pipiens it is 4.8 and higher, the rare
      populations with the intermediate indexes require the additional biological
      study.

PMID- 7816514
TI  - Erythroid transcription factor NF-E2 coordinates hemoglobin synthesis.

PMID- 7816515
TI  - Compartmental analysis of calcium metabolism in very-low-birth-weight infants.
AB  - The calcium metabolism of 13 very-low-birth-weight infants fed a high-calcium
      diet was evaluated by means of stable isotope kinetic and balance studies. The
      studies used orally and i.v. administered stable isotopes, and the kinetic data
      were evaluated with the aid of a sequential, three-compartment model. The infants
      (postmenstrual age 33 +/- 1 wk, weight 1.34 +/- 0.03 kg) had higher bone calcium
      deposition rates (160 +/- 7 mg.kg-1.d-1 or 4.00 +/- 0.18 mmol.kg-1.d-1) than
      those previously reported for either older children or adults. Furthermore, when
      analyzed as a function of net calcium absorption, bone calcium deposition rates
      increased markedly and significantly as net calcium absorption increased (r =
      0.70, p < 0.01), whereas in older individuals, bone calcium deposition is a
      relatively invariant function of absorption. A relatively smaller response of
      bone calcium removal to calcium absorption was found for the very-low-birth
      weight infants in this study (r = -0.39, p = 0.18), whereas in adults, bone
      calcium removal constitutes the major regulatory response. It is suggested that
      the calcium kinetic results in the very-low-birth-weight infants reflect the high
      rate of bone growth typical of the third trimester of gestation.

PMID- 7816516
TI  - Effect of enteral versus parenteral feeding on leucine kinetics and fuel
      utilization in premature newborns.
AB  - To determine whether the route of nutrient delivery affects whole-body protein
      kinetics and fuel utilization, eight premature newborns were studied during both
      a 4-h period of enteral intake and a 4-h period of parenteral nutrition. The
      kinetics of the essential amino acid leucine were measured using a constant
      tracer infusion of 1-13C-leucine, and fuel utilization and energy expenditure
      were assessed by respiratory calorimetry. All leucine kinetic parameters were
      similar during enteral or parenteral nutrition (in mean +/- SD mumol/kg/h, flux =
      233 +/- 51 enteral versus 258 +/- 42 parenteral, leucine from protein breakdown =
      177 +/- 50 enteral versus 200 +/- 41 parenteral, leucine oxidation = 57 +/- 26
      enteral versus 63 +/- 20 parenteral, and leucine used for protein synthesis = 176
      +/- 63 enteral versus 196 +/- 50 parenteral). In addition, overall rates of
      energy expenditure (approximately 52 kcal/kg/d) and pattern of fuel utilization
      (approximately 70% carbohydrate, 13% fat, 17% protein) were unaltered by the
      route of feeding. Thus, as reflected by leucine kinetics, overall rates of
      protein turnover, synthesis, oxidation, and breakdown as well as energy
      expenditure and fuel utilization are similar when nutrition is provided to
      premature newborns by either the enteral or parenteral route. These results
      suggest that short-term provision of parenteral nutrition may be able to
      substitute appropriately for enteral intake, at least with regard to the
      utilization of one essential amino acid and the overall pattern of fuel
      utilization.

PMID- 7816517
TI  - Changes of liver metabolite concentrations in adults with disorders of fructose
      metabolism after intravenous fructose by 31P magnetic resonance spectroscopy.
AB  - A novel 31P magnetic resonance spectroscopy procedure allows the estimation of
      absolute concentrations of certain phosphorus-containing compounds in liver. We
      have validated this approach by measuring ATP, phosphomonesters, and inorganic
      phosphate (Pi) during fasting and after an i.v. fructose bolus in healthy adults
      and in three adults with disorders of fructose metabolism and by comparing
      results with known metabolic concentrations measured chemically. During fasting,
      the ATP concentration averaged 2.7 +/- 0.3 (SD, n = 9) mmol/L, which, after due
      correction for other nucleoside triphosphates, was 2.1 mmol/L and corresponded
      well with known concentrations. Fructose-1-phosphate (F-1-P) could not be
      measured during fasting; its concentration after fructose was calculated from the
      difference of the phosphomonester signals before (2.9 +/- 0.2 mmol/L) and after
      fructose. Pi was 1.4 +/- 0.3 mmol/L and represented the one fourth of Pi visible
      in magnetic resonance spectra. In the three healthy controls after fructose (200
      mg/kg, 20% solution, 2.5 min), the fructokinase-mediated increase of F-1-P was
      rapid, reaching 4.9 mmol/L within 3 min, whereas the uncorrected ATP decreased
      from 2.7 to 1.8 mmol/L and the Pi from 1.4 to 0.3 mmol/L. The subsequent decrease
      of F-1-P, mediated by fructaldolase, was accompanied by an overshooting rise of
      Pi to 2.7 mmol/L. In the patient with essential fructosuria, the concentrations
      of F-1-P, ATP, and Pi remained unchanged, confirming that fructokinase was indeed
      inactive. In the patient with hereditary fructose intolerance, initial metabolic
      changes were the same as in the controls, but baseline concentrations were not
      yet reestablished after 7 h, indicating weak fructaldolase activity.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7816518
TI  - Prenatal diagnosis of collagen disorders by direct biochemical analysis of
      chorionic villus biopsies.
AB  - We have developed a method for early prenatal diagnosis of molecular disorders of
      collagens I and III. The method takes advantage of the fact that isolated
      chorionic villi contain significant amounts of collagens in their extracellular
      matrix (stroma) and that they synthesize collagens in vitro. After metabolic
      labeling of chorion villus biopsies in toto with radioactive amino acids,
      collagens are extracted and analyzed by SDS-PAGE. Direct staining of the gel
      shows collagens synthesized in vivo, whereas autoradiofluorography identifies
      collagens synthesized during incubation in vitro. Unlike collagens synthesized by
      cultured amniotic fluid cells, collagens extracted from chorionic villi are not
      overmodified and thus allow better identification of molecular defects. Results
      are available within 3 to 5 d after biopsy. Using this method, we have correctly
      excluded Ehlers-Danlos syndrome type IV in two pregnancies, Ehlers-Danlos
      syndrome type VII in one pregnancy, and lethal osteogenesis imperfecta in four
      pregnancies. In addition, we correctly predicted a healthy fetus and an embryo
      affected with lethal osteogenesis imperfecta in consecutive pregnancies from a
      couple in which the asymptomatic mother was a somatic mosaic for a COL1A1 G-to-A
      transition (Gly355Asp). Direct collagen analysis of chorion villus biopsies
      labeled in toto is rapid and reliable and may become the method of choice for the
      prenatal diagnosis of selected collagen disorders.

PMID- 7816519
TI  - Impaired degradation of prostaglandins and thromboxane in Zellweger syndrome.
AB  - Cyclooxygenase products are metabolized by omega-oxidation as well as beta
      oxidation. Children with Zellweger syndrome (ZS) are characterized by peroxisome
      deficiency. To evaluate the role of peroxisomal beta-oxidation on cyclooxygenase
      metabolites, the degradation of endogenous prostaglandin (PG) E2, prostacyclin,
      and thromboxane (Tx) A2 was assessed in children with ZS (n = 7) and in healthy
      children (n = 7). PGE2, prostacyclin, TxB2, and their major urinary metabolites 7
      alpha-hydroxy-5,11-dioxo-tetranor-prosta-1,16-dioic acid, 2,3-dinor-6-oxo-PGF1
      alpha, and 2,3-dinor-TxB2, respectively, were measured in urine by gas
      chromatography-mass spectrometry/mass spectrometry. The median excretion of
      healthy children was 17.9 ng of 7 alpha-hydroxy-5,11-dioxo-tetranor-prosta-1,16
      dioic acid/mg creatinine (interquartile range, 6.3 to 19.4 ng/mg), 0.38 ng of 2,3
      dinor-6-oxo-PGF1 alpha/mg creatinine (interquartile range, 0.34 to 0.70 ng/mg),
      and 0.36 ng of 2,3-dinor-TxB2/mg creatinine (interquartile range, 0.14 to 0.54
      ng/mg). In contrast, none of these metabolites could be detected in urine of
      children with ZS (p < 0.002). However, we identified in the urine of these
      children a new metabolite of PGE2 as 11-hydroxy-9,15-dioxo-prost-5-en-1,20-dioic
      acid by gas chromatography-mass spectrometry, and we confirmed the presence of
      9,11-dihydroxy-15-oxo-prost-5-en-1,20-dioic acid the main urinary metabolite of
      PGF2 alpha in ZS. Importantly, these two metabolites were only detectable in
      urine of children with ZS.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7816520
TI  - Epstein-Barr virus-infected marmoset cells do not form lymphomas in mice with
      severe combined immunodeficiency.
AB  - EBV has been associated with several malignancies in humans. EBV can also infect
      marmoset B lymphocytes, which, as opposed to human B cells, are permissive for
      lytic Epstein-Barr viral replication. Mice with a severe combined
      immunodeficiency phenotype (SCID mice) are extremely susceptible to EBV-induced
      lymphomagenesis when inoculated with EBV-infected lymphocytes. We inoculated SCID
      mice with human and marmoset lymphoblastoid cells infected with the same EBV
      isolates. The marmoset cells never gave rise to lymphomas, even after the
      administration of acyclovir or an anti-natural killer cell antibody and
      observation periods of up to 16 wk. In contrast, the human lymphoblastoid cells
      nearly always gave rise to lymphomas within 8 wk. Furthermore, human
      lymphoblastoid cells genetically engineered to permit lytic EBV replication also
      readily formed tumors in the SCID mouse. Thus, in this system, it is the cellular
      milieu that is crucial in determining whether a given lymphoblastoid cell will
      give rise to a tumor, not the EBV isolate harbored by the cell or whether the
      virus is permitted to undergo lytic replication.

PMID- 7816521
TI  - Na+/Ca2+ exchange, Ca2+ binding, and electrogenic Ca2+ transport in plasma
      membranes of human placental syncytiotrophoblast.
AB  - To transfer a large amount of Ca2+ to the fetus, the basal (fetal-facing) plasma
      membrane (BPM) of human placenta must be equipped with various extrusion
      mechanisms. We studied one such mechanism, Na+/Ca2+ exchange, as well as related
      membrane potential effects and binding properties of the two membranes. Na+/Ca2+
      exchange was present in BPM and absent in microvillous (maternal-facing)
      membrane. Uptake and efflux of Ca2+ in BPM were enhanced by Na+ when it was
      present on the opposite side of the membranes. Na(+)-gradient-dependent Ca2+
      uptake was saturable with a Km of 19 microM and a Vmax of 0.8 nmol/min/mg. The
      Na+/Ca2+ exchange in BPM and the facilitated diffusion transporters in both BPM
      and microvillous membrane are electrogenic processes. Ca2+ binding in both BPM
      and microvillous membrane was affected by various monovalent cations and enhanced
      by Na+ more than by K+. In vivo, together with other sequestration mechanisms,
      Na+/Ca2+ exchange may play an important role in transsyncytial transfer and in
      regulating intracellular Ca2+, which is essential for a variety of physiologic
      mechanisms.

PMID- 7816522
TI  - Effects of dioxins and polychlorinated biphenyls on thyroid hormone status of
      pregnant women and their infants.
AB  - Dioxins [polychlorinated dibenzo-p-dioxins (PCDD), dibenzofurans (PCDF)] and
      polychlorinated biphenyls (PCB) are potentially hazardous compounds. Animal
      studies have demonstrated that PCDD, PCDF, and PCB can alter thyroid hormone
      homeostasis. We investigated thyroid hormone levels in 105 mother-infant pairs.
      To estimate maternal and infant exposure, four nonplanar PCB congeners were
      measured in maternal plasma during the last month of pregnancy and in umbilical
      cord plasma. Seventeen PCDD and PCDF congeners, three planar PCB congeners, and
      23 nonplanar PCB congeners were measured in human milk. Higher PCDD, PCDF, and
      PCB levels in human milk, expressed as toxic equivalents, correlated
      significantly with lower plasma levels of maternal total triiodothyronine and
      total thyroxine, and with higher plasma-levels of TSH in the infants in the 2nd
      wk and 3rd mo after birth. Infants exposed to higher toxic equivalents levels had
      also lower plasma free thyroxine and total thyroxine levels in the 2nd wk after
      birth. We conclude that elevated levels of dioxins and PCB can alter the human
      thyroid hormone status.

PMID- 7816523
TI  - Bradykinin receptor blockade does not affect oxygen-mediated pulmonary
      vasodilation in fetal lambs.
AB  - Both oxygenation and rhythmic stretching of the lungs are factors known to be
      responsible for pulmonary vasodilation at birth. Based on our previous studies,
      we proposed that the pulmonary vasodilation caused by oxygen could be mediated,
      at least in part, through bradykinin release. To test this hypothesis, we
      evaluated the cardiovascular responses to in utero ventilation during infusion of
      a B2-subtype bradykinin receptor antagonist (BKA), [N-adamantaneacetyl-D
      Arg0,Hyp3,Thi5,8,D-Phe7]bradykinin, at 15-20 micrograms.kg-1.min-1 in eight near
      term fetal lambs and during drug vehicle infusion in five control fetal lambs.
      Prostacyclin synthesis was inhibited by meclofenamate infusion (1.5 mg.kg-1.h-1).
      Surgical placement of vascular catheters, a flow transducer around the left
      pulmonary artery, and a tracheostomy tube and formalin infiltration of the ductus
      arteriosus to maintain its patency in the presence of meclofenamate were
      performed 72 h before the study. Hemodynamic variables and pulmonary blood flow
      were measured and pulmonary vascular resistance was calculated before and after
      in utero ventilation with 100% oxygen. Despite complete blockade by BKA of the
      pulmonary vasodilation produced by exogenous bradykinin, ventilation with oxygen
      significantly increased pulmonary blood flow by 676% over baseline state (157.8
      +/- 66 to 1224 +/- 265 mL.min-1.100 g-1, p < 0.01) and decreased the pulmonary
      vascular resistance by 89% from baseline state (0.44 +/- 0.16 to 0.048 +/- 0.01
      torr.mL-1.min.100 g, p < 0.01). Such responses to ventilation with oxygen were
      comparable to those noted in the control animals, in whom bradykinin receptors
      had not been blocked.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7816524
TI  - Evidence for increased oxidative damage in patients with cystic fibrosis.
AB  - Patients with cystic fibrosis (CF) may be more susceptible to oxidative cell
      injury than normal healthy children due to both the impaired absorption of
      antioxidant nutrients and the increased oxidative stress caused by chronic
      pulmonary infections. The purpose of this study was to examine whether markers of
      oxidative damage to lipids (malondialdehyde-like substances and lipid
      hydroperoxides) and proteins (protein carbonyls) were present in the plasma of CF
      patients. Mean values (+/- SD) of thiobarbituric acid-reactive substances were
      significantly higher in patients (6.93 +/- 1.47 mumol/L; n = 25) than in controls
      (5.84 +/- 0.59 mumol/L; n = 10). FFA hydroperoxides were not detected in control
      subjects (the detection limit of the assay was 0.02 mumol/L), but in 11 of the 33
      CF patients studied they were found in a range of 0.03-0.34 mumol/L. Plasma
      protein carbonyl concentrations did not differ significantly between the two
      groups (p = 0.076), although a much wider distribution was observed in the CF
      patients (range 0.17-5.64 nmol/mg protein) than in the control group (range 0.24
      1.55 nmol/mg protein). No correlation was found between thiobarbituric acid
      reactive substances and FFA hydroperoxides or between either of these markers and
      protein carbonyl content. Concentrations of plasma vitamin E, vitamin C, and
      protein sulfhydryls were within the normal ranges in both control subjects and CF
      patients. The concentration of uric acid was significantly reduced (p < 0.01) in
      the CF group (204 +/- 96.99 mumol/L) compared with that in control subjects (352
      +/- 81.11 mumol/L), but reduction in plasma levels of this antioxidant did not
      correlate with increased markers of free radical damage.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7816525
TI  - Surfactant therapy and high-frequency jet ventilation in the management of a
      piglet model of the meconium aspiration syndrome.
AB  - In vitro data have shown a concentration-dependent inhibition of surfactant by
      meconium, while anecdotal reports demonstrate improved oxygenation after
      surfactant replacement in babies with meconium aspiration syndrome, particularly
      in conjunction with high-frequency jet ventilation. We randomized 70 newborn
      piglets to either conventional or high-frequency jet ventilation, followed by
      insufflation of 3 mL/kg of a 33% meconium solution. Each group was further
      randomized to one of five surfactant therapies: 1) control, 2) 4 mL/kg Survanta,
      3) 8 mL/kg Survanta, 4) 5 mL/kg Exosurf, or 5) 10 mL/kg Exosurf. We followed
      arterial blood gases and ventilator requirements over 6 h of ventilation.
      Aspirates of airway fluids were obtained for surface tension measurements, as
      well as total protein and phospholipid concentrations. Using a previously
      established scoring system, a pathologist blinded to treatment evaluated four
      sections of lung per animal for histologic changes of meconium aspiration
      syndrome. There were no differences noted between groups in any physiologic
      parameter measured (mean airway pressure, arterial partial pressure of
      oxygen/alveolar partial pressure of oxygen ratio, etc.) during the 6 h of
      ventilation. Airway fluid aspirate total protein concentrations increased
      significantly after meconium instillation (4- to 5-fold, p < 0.007) and remained
      elevated in spite of surfactant therapy. There was an initial decline in airway
      phospholipid concentrations after meconium instillation followed by a rise to
      levels equal to or greater than premeconium levels. Surface tension measurements
      increased in all groups after meconium insufflation (p < 0.012) and did not
      decline thereafter, despite standard and twice-standard surfactant doses of both
      types.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7816526
TI  - Arousal response from sleep to tracheal obstruction in lambs during postnatal
      maturation.
AB  - Experiments were carried out to investigate the arousal response from sleep to
      tracheal obstruction in lambs during postnatal maturation. Ten fetal sheep were
      instrumented with electrodes for sleep staging and a tracheotomy was done. After
      spontaneous vaginal delivery, serial experiments were carried out on the lambs at
      five postnatal ages: 18-48 h and 4, 6, 11, and 18 d. During an experiment, a 5F
      balloon-tipped catheter was inserted into the tracheostomy tube so that tracheal
      obstruction could be produced by inflating the balloon. Measurements were made in
      quiet sleep and active sleep during control periods of tidal respiration and
      during experimental periods of tracheal obstruction. Neither sleep state nor age
      influenced control arterial Hb oxygen saturation (SaO2). SaO2 decreased
      significantly before arousal during tracheal obstruction in quiet sleep at 18-48
      h and in active sleep at all ages. The SaO2 at arousal was always lower in active
      sleep than in quiet sleep. Overall, however, there were no significant effects of
      age on the change in SaO2 before arousal in either quiet sleep or active sleep.
      The time to arousal during tracheal obstruction increased between 18-48 h and 6 d
      of postnatal life in active sleep but not in quite sleep. Our data provide
      evidence that the arousal response to tracheal obstruction is functional by 18 h
      of postnatal life in lambs. The increase in time to arousal after tracheal
      obstruction in active sleep most likely results from state-specific changes in
      the factors governing oxygen supply and demand.

PMID- 7816527
TI  - Changes in renal function and blood volume in the newborn lamb delivered by
      cesarean section.
AB  - To determine the cause of the transient natriuresis in lambs within 1-2 h of
      birth, renal function and blood volume (BV) were measured in nine chronically
      catheterized fetal sheep aged 139-145 d before and after delivery by cesarean
      section. After delivery, sodium excretion increased 8-fold. This was due to a
      transient rise in glomerular filtration rate (by 39 +/- 21%, p < 0.02) and a fall
      in fractional reabsorption of sodium by the proximal tubule from 63.4 +/- 2.5% to
      53.4 +/- 3.4% (p < 0.01). The distal tubule failed to compensate fully for this
      fall, because fractional reabsorption by the distal tubule rose from 35.5 +/-
      2.4% to only 41.6 +/- 2.2% (p < 0.05). The extent of the natriuresis did not
      depend on the lamb's initial BV per kg at birth. However, the amount of fluid
      excreted and the clearance of sodium during a 45-min period within the first 1
      1.25 h after birth were approximately equal to the fall in BV that occurred
      during this time. Thus, most of the fall in BV that occurs after delivery is due
      to renal salt and water losses. Because the natriuresis was greater if the lamb's
      arterial pressure rose after birth, it is possible that a high arterial pressure
      in the immediate newborn period could result in salt and volume depletion.

PMID- 7816529
TI  - Saccharomyces boulardii enhances rat intestinal enzyme expression by endoluminal
      release of polyamines.
AB  - Saccharomyces boulardii is a yeast widely used in humans for the prevention and
      treatment of infectious enteritis and Clostridium difficile-associated
      enterocolopathies. After oral administration to human volunteers or growing rats,
      S. boulardii enhances markedly the expression of intestinal enzymes as well as
      the production of the polymeric immunoglobulin receptor by mechanisms that remain
      unknown. We have analyzed the role of the yeast polyamines as potential mediators
      in the intestinal trophic response. In weanling rats (d 20 to d 30), a daily dose
      of 100 mg of lyophilized S. boulardii produced significant (p < 0.025) increases
      in sucrase (157%) and maltase (47%) activities. This dose corresponded to a total
      oral load of 678 nmol of polyamines per day (spermidine; 376 +/- 32, spermine:
      293 +/- 26, putrescine: 9.5 +/- 1.4 nmol/100 mg). Spermine, given orally to
      growing rats at doses nearly equivalent (500 nmol) to the load of polyamines
      provided by the yeast (678 nmol), reproduced similar enzymatic changes, including
      a 2.5-fold induction of sucrase, and enhanced maltase activity (+24%). Spermidine
      and spermine concentrations measured in the jejunal mucosa of treated rats were
      increased over matched controls by 21.4% (p < 0.005) and 21.9%, respectively (p <
      0.002). After being centrifuged and filtered to discard residual yeast cells, 2
      mL samples of jejunal and ileal fluid collected from S. boulardii-treated rats by
      intestinal flushing contained higher levels of spermidine (48 and 60%) and
      spermine (150 and 316%) than did control rats. Our data indicate that lyophilized
      S. boulardii exerts trophic effects on the small intestine that are likely
      mediated by the endoluminal release of spermine and spermidine.

PMID- 7816528
TI  - Expression of human intestinal mRNA transcripts during development: analysis by a
      semiquantitative RNA polymerase chain reaction method.
AB  - To study the relative expression of lactase, sucrase-isomaltase, dipeptidyl
      peptidase IV, and the Na(+)-dependent glucose transporter mRNA transcripts in
      small samples of human tissue, we have developed and validated a very simple
      semiquantitative RNA polymerase chain reaction method that can be used on as
      little as 5-10 mg of tissue. Here we report the use of this method to study the
      expression of these genes at different stages of development, in different
      tissues and in different parts of the intestine, in comparison with another
      intestinal marker, the colon-specific transcript of carbonic anhydrase 1.
      Lactase, sucrase-isomaltase, and the Na(+)-dependent glucose transporter mRNA are
      expressed predominantly in the small intestine, although lactase mRNA is
      expressed at a very low level in fetuses. Dipeptidyl peptidase IV mRNA shows a
      much wider tissue distribution. Sucrase-isomaltase and dipeptidyl peptidase IV
      mRNA are present at high levels in fetal colon and also at surprisingly high
      levels in adult colon. Lactase mRNA, on the other hand, is present at very low
      levels in fetal colon and is not detectable at all in adult colon. The Na(+)
      dependent glucose transporter mRNA in contrast is expressed at higher levels in
      the adult colon than in the fetal colon. This is also the case for the carbonic
      anhydrase 1 transcript, although this transcript is not expressed in the small
      intestine. Thus, each of these genes shows different developmental and cell
      specific regulation.

PMID- 7816530
TI  - Malabsorption in infants with congenital heart disease under diuretic treatment.
AB  - Intestinal absorption and its relationship to increased total body water was
      studied in seven infants with congenital heart disease receiving regular
      diuretics due to congestive heart failure. All infants and six age-matched
      healthy controls were studied for a 3-d period during which time all food intake
      was recorded, stools were collected, and total body water content (TBW) and
      extracellular water were measured. All the anthropometric measurements were lower
      in the infants with congenital heart disease compared with healthy controls.
      Energy and fat excretion in the stools were significantly increased in the group
      of patients, but when expressed as a percentage of daily caloric intake or as a
      percentage of the specific intake (e.g. fat excretion/fat intake x 100), no
      statistical differences were found. TBW as a percentage of body weight was
      increased in our patients compared with our controls (84.95 +/- 5.82% versus
      68.65 +/- 4.60%; p = 0.01) and so was extracellular water as a percentage of
      predicted (200.0 +/- 18.6% versus 100.9 +/- 7.2%; p = 0.001). A positive
      correlation was found between energy and fat excretion as a percentage of the
      intake and TBW as a percentage of predicted; energy and fat malabsorption did not
      exceed 8% in the patients with the highest body water content (120% of
      predicted). It is concluded that malabsorption is not a significant factor in
      failure to thrive of patients with congenital heart disease who are receiving
      regular diuretics. Based on the significant negative correlation between excess
      body water and fat and calorie absorption, however, it is suggested to monitor
      TBW in patients who fail to gain weight.

PMID- 7816531
TI  - Very immature infants (< or = 30 Wk) respond to glucose infusion with incomplete
      suppression of glucose production.
AB  - Small substrate stores and immature enzyme systems make preterm infants prone to
      develop hypoglycemia. Hyperglycemia may also occur, particularly when these
      infants are given i.v. glucose. To evaluate the capacity for regulation of
      glucose production in response to glucose infusion, 10 newborn infants, born
      after 25-30 wk of gestation, were studied. Their glucose production rates (GPR)
      were calculated and the concentrations of glucose, insulin, and glucagon in
      plasma were measured during infusion of glucose at a rate of first 1.7 +/- 0.2
      and then 6.5 +/- 0.3 mg.kg-1.min-1 (9.4 +/- 1.1 and 36.1 +/- 1.7 mumol.kg-1.min
      1) (mean +/- SD). GPR was determined by use of D-6,6-2H2-glucose. When the rate
      of infusion of glucose was increased, GPR decreased from 4.3 +/- 1.3 to 1.4 +/-
      1.1 mg.kg-1.min-1 (23.9 +/- 7.2 to 7.8 +/- 6.1 mumol.kg-1.min-1) (mean +/- SD) (p
      = 0.00006). In addition, the plasma insulin concentration increased from 6 +/- 2
      to 11 +/- 4 microU.mL-1 (p = 0.006) and the plasma glucose concentration from 3.6
      +/- 1.1 to 6.1 +/- 1.3 mM (mean +/- SD) (p = 0.0002), whereas the glucagon
      concentration remained unchanged. Only the insulin concentration in plasma was
      significantly related to GPR. The results show that very immature newborn infants
      have an incomplete and varying capacity to respond to glucose infusion with
      suppression of glucose production. Insulin seems to be more important than plasma
      glucose in the regulation of glucose homeostasis in these infants.

PMID- 7816533
TI  - Vertical similarity in spoken word recognition: multiple lexical activation,
      individual differences, and the role of sentence context.
AB  - Four experiments investigated acoustic-phonetic similarity in the mapping process
      between the speech signal and lexical representations (vertical similarity).
      Auditory stimuli were used where ambiguous initial phonemes rendered a phoneme
      sequence lexically ambiguous (perceptual-lexical ambiguities). A cross-modal
      priming paradigm (Experiments 1, 2, and 3) showed facilitation for targets
      related to both interpretations of the ambiguities, indicating multiple
      activation. Experiment 4 investigated individual differences and the role of
      sentence context in vertical similarity mapping. The results support a model
      where spoken word recognition proceeds via goodness-of-fit mapping between speech
      and lexical representations that is not influenced by sentence context.

PMID- 7816532
TI  - Two-month-old infants' sensitivity to allophonic differences.
AB  - The present study investigated 2-month-olds' abilities to discriminate allophonic
      differences that are potentially useful in segmenting fluent speech. Experiment 1
      investigated infants' sensitivity to the kind of distinction that may signal the
      presence or absence of a word boundary. When tested with the high-amplitude
      sucking procedure, infants discriminated pairs of items, such as "nitrate" versus
      "night rate" and "nikrate" versus "nike rate". By greatly reducing the potential
      contribution of prosodic differences to these contrasts, Experiment 2 evaluated
      whether the allophonic differences for /t/ and /r/ were sufficient for infants to
      distinguish the "nitrate" versus "night rate" pair. Infants distinguished
      "nitrate" from a cross-spliced version of "night rate," which differed only in
      the allophones for /t/ and /r/ that it included. Thus, infants appear to possess
      one of the prerequisite capacities (i.e., the ability to discriminate allophonic
      distinctions) necessary to use allophonic information in segmenting fluent
      speech.

PMID- 7816535
TI  - Contrasting task demands alter the perceived duration of brief time intervals.
AB  - Four experiments were performed to assess the effects of task differences on
      duration judgments. Experiments 1 and 2 used the method of reproduction in
      prospective, within-subjects designs; their results supported previous research
      on the effects of task difficulty. Both experiments, using tasks that varied
      along somewhat different dimensions, found that subjects provided reproduction
      values that varied inversely with task difficulty. That is, while subjects tended
      to underreproduce across all tasks, the more difficult the task performed during
      the target interval, the greater the extent of the underreproduction. Experiments
      3 and 4 used a modification of the reproduction method by placing demands upon
      the subjects during both the target interval and the reproduction phase of each
      trial; they demonstrated that the greater the degree of contrast between demands
      made by the task performed during the target interval and those made during
      reproduction, the less accurate the duration reproduction. The results are
      discussed in terms of the contextual and resource allocation models of duration
      estimation.

PMID- 7816534
TI  - Iontophoretically applied potassium ions as an experimental pain stimulus for
      investigating pain mechanisms.
AB  - The present study investigated the psychophysical characteristics of potassium
      iontophoresis and its suitability as an experimental pain stimulus. Experiment 1
      investigated the optimal duration of the pain stimulus for reliable reporting
      across repeated trials and whether the relationship between stimulus and subject
      response was linear, logarithmic, or a power function. In Experiment 2, the
      optimal interstimulus interval (ISI) was determined for reliable pain reporting,
      and stimulus history effects, both in terms of session effects and the effects of
      immediately preceding stimuli, were evaluated. In Experiment 3, potassium
      iontophoresis was compared with a sodium iontophoresis control. Linear functions
      described the stimulus-pain relationship best. No significant differences in the
      goodness-of-fit coefficients of determination, correlations, or coefficients of
      variation were found for the stimulus durations of 1, 2, and 4 sec. Significant
      stimulus history effects were found across a session, with adaptation and
      enhancement of responding for low- and moderate-intensity stimuli, respectively.
      The effects of the immediately preceding stimuli were suppression or enhancement
      of pain response, depending on the ISI, the preceding stimulus intensity, and the
      present stimulus intensity. Potassium iontophoresis was a significantly more
      effective pain stimulus than was sodium iontophoresis. It was concluded that
      potassium iontophoresis is a convenient and reliable experimental pain stimulus,
      which can be presented rapidly and repeatedly with minimal loss in consistency of
      subject pain report. Potassium iontophoresis provides a tool for investigating
      the neural modulation of pain in the relative absence of inflammation processes
      and tissue damage.

PMID- 7816536
TI  - Very short term recognition memory for odors.
AB  - An investigation of very short term olfactory recognition memory was made with
      odors of low familiarity to subjects. The experimental procedure was that
      currently used to make qualitative similarity judgments on odors delivered in
      paired succession. Subjects made similarity judgments in a yes/no recognition
      paradigm on odors that were either identical or different. The dependence of
      recognition performance upon the degree of qualitative similarity was assessed by
      using two sets of dissimilar odor pairs: slightly dissimilar pairs (S1) and very
      dissimilar pairs (S2). Performance in terms of correct judgments (hits, correct
      rejections) was rather good for identical pairs in both sets and was nearly
      perfect for very dissimilar pairs with a delay of 2-300 sec, suggesting no effect
      of time or similarity on performance. However, for slightly dissimilar pairs,
      false alarms increased in number, thereby indicating a dependence of the
      recognition score on the qualitative distance between odors. In addition, false
      alarms tended to increase with the lengthening of the retention interval. It was
      suggested that the subjects based their responses on their capability to detect
      differences between odors rather than recognizing their similarities. Correct
      identifications were thus preserved at the cost of increasing false alarms when
      the discrimination task was made more difficult by closer similarity between
      odors (S1) or by the fading of memory traces with time. Studying the congruence
      between the similarity judgments and the kind of evocations associated with
      paired odors gives some support to the view that recognition performances had
      some cognitive/semantic basis.

PMID- 7816537
TI  - Inhibition and disinhibition of return: evidence from temporal order judgments.
AB  - In the present study the temporal order judgment (TOJ) task was used to
      investigate whether or not inhibition of return (IOR) affects perceptual
      processing. Previous failures to obtain IOR in the TOJ task have been taken to
      suggest that IOR does not affect perceptual processing (e.g., Maylor, 1985). The
      present study showed that IOR is modulated by the temporal disparity between
      successive targets as well as the relative order in which they appear at cued and
      uncued locations. Consequently, IOR affects TOJs in some conditions but not in
      others. The selective occurrence of IOR in the TOJ task provides converging
      support for the notion that IOR does affect perceptual processing, and also
      accounts for the previous failures to observe IOR in the TOJ task. Moreover,
      these and other results suggest that inhibitory processing at the cued location
      can be disinhibited when stimulation occurs at other locations.

PMID- 7816538
TI  - Size scaling and its effect on letter detection.
AB  - Two ways of scaling letter size across eccentricity were investigated in a choice
      reaction time (CRT) task. Experiments 1 and 2 tested cortical magnification
      theory (M-scaling), while Experiment 3 used scaled sizes drawn from Anstis's
      regression formula (A-scaling). Experiment 4 compared both scaling techniques,
      together with the effect of exposure duration and the absolute size of the foveal
      letter. Results showed that scaling effectiveness improved when large rather than
      small foveal letters were used. A-scaling with a large foveal letter provided a
      good fit for the data at parafoveal locations, but underestimated the letter
      sizes needed at large eccentricities. M-scaling with a large foveal letter size
      produced CRTs that were independent of eccentricity. Exposure duration did not
      substantially affect performance.

PMID- 7816539
TI  - The effect of gap depth on the perception of whether a gap is crossable.
AB  - Four experiments were performed in order to examine the effect of gap depth on
      human observers' perception of whether or not a gap is crossable. Experiments 1
      and 2 showed that as the gap's depth increased, observers tended to increasingly
      underestimate the maximum width of a gap they could step across. Experiments 3
      and 4 clarified this finding: The observed covariation of perceived gap
      crossability and gap depth depended on the observer's direction of gaze, rather
      than on the physical depth of the gap. The optical relations to which observers
      might be attending are discussed, as well as the possibility that cognitive
      affective processes might have contributed to observers' underestimation of their
      actual capabilities.

PMID- 7816540
TI  - Tests of human olfactory function: principal components analysis suggests that
      most measure a common source of variance.
AB  - It is not known whether nominally different olfactory tests actually measure
      dissimilar perceptual attributes. In this study, we administered nine olfactory
      tests, including tests of odor identification, discrimination, detection, memory,
      and suprathreshold intensity and pleasantness perception, to 97 healthy subjects.
      A principal components analysis performed on the intercorrelation matrix revealed
      four meaningful components. The first was comprised of strong primary loadings
      from most of the olfactory test measures, whereas the second was comprised of
      primary loadings from intensity ratings given to a set of suprathreshold odorant
      concentrations. The third and fourth components had primary loadings that
      reflected, respectively, mean suprathreshold pleasantness ratings and a response
      bias measure derived from a yes/no odor identification signal detection task. In
      an effort to adjust for potential confounding influences of age, gender, smoking,
      and years of schooling on the component structure, a matrix of residuals from a
      multiple regression analysis, which included these variables, was also analyzed.
      A similar component pattern emerged. Overall, these findings suggest, in healthy
      subjects spanning a wide range, that (1) a number of nominally distinct tests of
      olfactory function are measuring a common source of variance, and (2) some
      suprathreshold odor intensity and pleasantness rating tests may be measuring
      sources of variance different from this common source.

PMID- 7816541
TI  - Heuristic judgment of mass ratio in two-body collisions.
AB  - The logic of judging relative mass from a two-body collision is developed from
      data presented by Runeson and Vedeler (1993). Data from two experiments are
      analyzed on a point-by-point basis, and strong support for the theory that mass
      ratio judgments are mediated by separate speed and angle heuristics is shown.
      This analysis is accomplished by reducing the collision event to two elementary
      features: the presence of ricochet and the ratio of exit speeds. The heuristics
      that both ricochet and greater exit speed specify relative lightness are shown to
      explain the basic patterns of data presented by Runeson and Vedeler.

PMID- 7816542
TI  - Circulating cytokine concentrations and cytokine production by monocytes from
      newborn babies and adults.
AB  - As a possible factor responsible for reduced fever responses in the newborn, we
      measured plasma cytokine concentrations and cytokine production by neonatal
      monocytes after lipopolysaccharide or IL (interleukin)-1 alpha stimulation in
      vitro and compared these data with those obtained from adult plasma and
      monocytes. Whole blood was collected from afebrile adults (n = 12) and the
      umbilical cord of normal term infants (n = 12). Plasma and peripheral blood
      monocytes were prepared by conventional techniques. Significantly lower
      concentrations of IL-1 alpha, IL-1 beta (P < 0.05, t-test) and IL-6 (P < 0.01, t
      test) were found in the plasma of newborn babies compared with that of adults.
      There was no significant difference in plasma tumour necrosis factor (TNF)
      concentrations between the adults and newborn babies. Monocytes from newborn
      babies had the capacity to produce IL-1 alpha and IL-1 beta as readily as adult
      cells after stimulation with lipopolysaccharide or IL-1 alpha, and produced
      significantly lower concentrations of TNF and IL-6 than those produced by
      stimulated adult monocytes (P < 0.01, ANOVA). Our results suggest that the
      reduced production of IL-6 by monocytes of the newborn during infection could be
      partly responsible for attenuated fever responses observed in the neonate.

PMID- 7816543
TI  - Modulation of the gating of the transient outward potassium current of rat
      isolated cerebellar granule neurons by lanthanum.
AB  - The effects of the trivalent cation, lanthanum (La3+) on voltage-dependent K+
      conductances were studied in rat isolated cerebellar granule neurons under whole
      cell voltage-clamp conditions. La3+ at low micromolar concentrations caused a
      pronounced enhancement in the outward current evoked by depolarising steps from 
      50 mV, with the apparent recruitment of an inactivating component. The steady
      state inactivation curve for the transient outward current, evoked by
      depolarising steps from -140 mV, was shifted by approximately 40 mV in the
      depolarising direction by 10 microM La3+, with a slight increase in the slope
      factor. The kinetics of activation and inactivation were slowed in the presence
      of La3+. A shift of 10 mV in the depolarising direction was seen for the
      activation curve of the delayed rectifier current in the presence of 10 microM
      La3+. These results indicate that La3+ has a potent effect on the gating
      characteristics of voltage-activated K+ currents. This effect cannot be explained
      by surface charge considerations.

PMID- 7816545
TI  - Effect of activation of protein kinase C on excitation-contraction coupling in
      frog twitch muscle fibres.
AB  - Intracellular Ca2+ transients were recorded from frog twitch muscle fibres in
      response to voltage-clamp depolarizing pulses, using arsenazo III as an
      intracellular Ca2+ indicator. The effect of the activation of protein kinase C
      (PKC) on the Ca2+ transients was studied. With 1 microM phorbol 12,13-dibutyrate
      (PDBu), a PKC activator, the peak of the Ca2+ transients increased to about 120%
      of control during the first 0.5 h, and then decreased gradually to a plateau of
      44% of control within the following 2 h. This effect of PDBu could be alleviated
      significantly by PKC inhibitors, 10 microM polymyxin B (PMB) or 30 microM 1-(5
      isoquinolinylsulphonyl)-2-methyl-piperazine (H-7). Moreover, PDBu caused an
      upward shift of the strength/duration curve. In Li(+)-loaded muscle fibres the
      Ca2+ transients could not fully recover after 80 mM K+ exposure for 15 min, while
      the post-K+ Ca2- transients could be completely restored in the fibres not loaded
      with Li+. In the presence of 10 microM PMB or 30 microM H-7, a full restoration
      of the post-K+ Ca2+ transients was seen in Li(+)-loaded fibres. PMB supplemented
      after high-K+ exposure also could result in a complete recovery of the post-K+
      Ca2+ transients in Li(+)-loaded fibres. The role of PKC in modulating excitation
      contraction coupling in frog twitch muscle fibres is clearly indicated, but the
      mechanism(s) and physiological significance remain to be established.

PMID- 7816544
TI  - cDNA cloning of a rat small-intestinal Na+/SO4(2-) cotransporter.
AB  - We have isolated a cDNA (ileal NaSi-1) from rat small intestine by homology
      screening with a cDNA (renal NaSi-1) encoding rat kidney cortex Na(+)-SO4(2-)
      cotransport. Ileal NaSi-1 cRNA specifically stimulates Na(+)-dependent SO4(2-)
      uptake in a time- and dose-dependent manner in Xenopus laevis oocytes, with
      kinetic parameters almost identical to those of the renal NaSi-1. Ileal NaSi-1
      cDNA contains 2722 base pairs (bp), almost 500 bp more than the renal NaSi-1
      cDNA; however, it encodes a protein of 595 amino acids identical to the renal
      NaSi-1 protein. Northern blot analysis shows strong signals in rat lower small
      intestine and kidney cortex (2.9 x 10(3) and 2.3 x 10(3) bases), with the ileal
      NaSi-1 corresponding to the longer transcript. We conclude that we have
      identified a rat ileal cDNA that encodes a membrane protein most likely involved
      in brush-border Na(+)-SO4(2-) cotransport. It differs to the renal NaSi-1 only in
      the length of the 3' untranslated region, suggesting that the major difference
      lies in the differential use of polyadenylation signals.

PMID- 7816546
TI  - Developmental changes in Ca2+ currents from newborn rat cardiomyocytes in primary
      culture.
AB  - Electrophysiological characteristics of neonatal rat ventricular cardiomyocytes
      in primary culture were studied using the whole-cell patch-clamp recording
      technique. Cell size, estimated by measurement of membrane capacitance, was
      significantly increased throughout the culture from 22.4 +/- 5.4 pF at day 2 to
      55.0 +/- 16.1 pF at day 7, reflecting the hypertrophic process which
      characterises postnatal cell development. The Ca2+ current was investigated at
      day 2 and 7 of the culture which constituted the early postnatal and maximally
      developed stages, respectively, of isolated cells in our experimental conditions.
      At 2 days of culture, two types of Ca2+ current could be distinguished, as also
      observed in freshly dissociated newborn ventricular cells. From their potential
      dependence and pharmacological characteristics, they could be attributed to the T
      (ICa-T) and L-type (ICa-L) Ca2+ current components. After 7 days of culture,
      only the latter ICa-L was present and its density was significantly increased
      when compared to the density in 2-day-old cells, but lower than that obtained in
      freshly dissociated adult cells. As the age of the culture progressed, the steady
      state inactivation curve was shifted toward negative potentials, in the direction
      of the inactivation curve obtained for adult cells. Compared to the serum-free
      control conditions, the density of ICa-L was significantly increased in the
      presence of fetal calf serum throughout the culture. Consequently, the density of
      ICa-L obtained in 7-day-old cells was similar to the density of ICa-L obtained in
      freshly dissociated adult cardiac cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7816547
TI  - Functionally intact in vitro preparation generating respiratory activity in
      neonatal and mature mammals.
AB  - The present report describes a novel rhythmically active brainstem slice
      preparation that generates respiratory activity spontaneously in both mice and
      rats of varying maturational states. The brainstems of neonatal (0-4 days) and
      mature (3-8 weeks) mice and rats were isolated and a 600- to 750-microns thick
      slice cut to include the dorsomedial and the ventrolateral regions of the
      complete rostro-caudal extent of the medulla. This plane of section we have
      termed "tilted-sagittal". Rhythmically discharging neurones were recorded
      extracellularly from both the dorsal and ventral regions of the slice. The
      recording sites of these neurones were found in the hypoglossal motonucleus (XII)
      and in areas of the ventrolateral medulla that includes the ventral respiratory
      group (VRG) region. Histological examination revealed the preservation of
      neuronal structures important for cardiorespiratory regulation and reflex control
      including the nucleus of the solitary tract as well as the nucleus ambiguus. In
      addition, pontine structures including the A5 region were also preserved.
      Rhythmic activity was found only in slices where the ambiguual column was
      preserved in its entirety. The mean frequency of discharge of XII neurones was 20
      and 10 bursts per minute in neonates and mature rodents respectively. In
      preparations of mature animals we demonstrate that this frequency increased
      significantly (P < 0.05) by either raising temperature from 29 degrees C to 38
      degrees C (54%), elevating extracellular potassium concentration from 4 to 7.5 mM
      (52%), blocking potassium channels (20%) or decreasing pH from 7.4 to 7.0 (18%).
      The burst duration to frequency ratio of XII and VRG rhythmic neurones was
      similar and therefore indicative of a common brainstem oscillator. Consistent
      with this finding was that rhythmic activity in the VRG persisted despite removal
      of the dorsomedial region of the slice. In contrast, rhythmic XII neurones became
      tonic following mechanical disconnection of the VRG.

PMID- 7816548
TI  - The control of chloride conductance in rat parotid isolated acinar cells
      investigated by photorelease of caged compounds.
AB  - The control of Cl- conductance in rat parotid isolated acinar cells was studied
      by combined use of whole-cell recording and flash photolysis techniques. Cells
      were voltage-clamped either at a membrane potential of -40 mV or stepped between 
      85 mV and 0 mV. Bath-applied carbachol and noradrenaline evoked Cl- current at 
      85 mV and K+ current at 0 mV. Similar current activations resulted from the
      photolytic release of either inositol trisphosphate (InsP3) or Ca2+ by a brief
      near-UV flash. The peak amplitudes of the Cl- conductance (at -85 mV), measured
      relative to the K+ conductance (at 0 mV), evoked by application of carbachol,
      noradrenaline or direct manipulation of cytosolic free calcium ([Ca2+]i), were
      very similar, being 0.56 +/- 0.09 (mean +/- SEM, n = 9), 0.52 +/- 0.01 (n = 7)
      and 0.46 +/- 0.06 (n = 7). In contrast, the relative amplitude of the Cl-
      conductance evoked by InsP3 was much larger: 1.49 +/- 0.24 (n = 9). Neither bath
      application of isoprenaline nor photolysis of "caged" cAMP induced any detectable
      membrane current. The most probable interpretation of these results is that the
      observed activation of Cl- conductance by agonists can be explained by the
      elevation of [Ca2+]i alone. In addition, the present results provide further
      support for the previously reported suggestion that the Cl- channels and the
      Ca(2+)-release sites are co-localised [10].

PMID- 7816549
TI  - Intracellular Ca2+ signals in human-derived pancreatic somatostatin-secreting
      cells (QGP-1N).
AB  - Single-cell microfluorimetry techniques have been used to examine the effects of
      acetylcholine (0.1-100 microM) on the intracellular free calcium ion
      concentration ([Ca2+]i) in a human-derived pancreatic somatostatin-secreting cell
      line, QGP-1N. When applied to the bath solution, acetylcholine was found to evoke
      a marked and rapid increase in [Ca2+]i at all concentrations tested. These
      responses were either sustained, or associated with the generation of complex
      patterns of [Ca2+]i transients. Overall, the pattern of response was
      concentration related. In general, 0.1-10 microM acetylcholine initiated a series
      of repetitive oscillations in cytoplasmic Ca2+, whilst at higher concentrations
      the responses consisted of a rapid rise in [Ca2+]i followed by a smaller more
      sustained increase. Without external Ca2+, 100 microM acetylcholine caused only a
      transient rise in [Ca2+]i, whereas lower concentrations of the agonist were able
      to initiate, but not maintain, [Ca2+]i oscillations. Acetylcholine-evoked Ca2+
      signals were abolished by atropine (1-10 microM), verapamil (100 microM) and
      caffeine (20 mM). Nifedipine failed to have any significant effect upon agonist
      evoked increases in [Ca2+]i, whilst 50 mM KCl, used to depolarise the cell
      membrane, only elicited a transient increase in [Ca2+]i. Ryanodine (50-500 nM)
      and caffeine (1-20 mM) did not increase basal Ca2+ levels, but the Ca(2+)-ATPase
      inhibitors 2,5-di(tert-butyl)-hydroquinone (TBQ) and thapsigargin both elevated
      [Ca2+]i levels. These data demonstrate for the first time cytosolic Ca2+ signals
      in single isolated somatostatin-secreting cells of the pancreas. We have
      demonstrated that acetylcholine will evoke both Ca2+ influx and Ca2+
      mobilisation, and we have partially addressed the subcellular mechanism
      responsible for these events.

PMID- 7816550
TI  - Vasopressin responses in electrically coupled A7r5 cells.
AB  - Changes in cytosolic Ca2+ concentration ([Ca2+]i) and in membrane potential were
      monitored in single A7r5 smooth-muscle cells during spontaneous spiking and after
      arginine vasopressin stimulation. Spontaneous Ca2+ oscillations, which were
      associated with the occurrence of action potentials, occurred in about 90% of the
      confluent monolayers investigated. This spontaneous activity was synchronized
      amongst all the cells of the monolayer, indicating that the cells were
      electrically coupled. Arginine vasopressin stimulation produced a [Ca2+]i rise
      that was about 5 times higher than the amplitude of the spontaneous Ca2+
      oscillations and resulted in a subsequent cessation of spontaneous electrical
      activity and associated Ca2+ spiking, which persisted after [Ca2+]i returned to
      baseline. Individual cells in the monolayer responded to arginine vasopressin
      with a different latency. Agonist-induced Ca2+ waves within one cell propagated
      much more slowly than spontaneous [Ca2+]i rises. We conclude that agonist-induced
      [Ca2+]i increases in an electrically coupled cell monolayer can be asynchronous.

PMID- 7816551
TI  - A voltage-sensitive transient potassium current in mouse pancreatic acinar cells.
AB  - We describe, for the first time, a potassium current in acutely isolated mouse
      pancreatic acinar cells. This current is activated by depolarization and has many
      of the characteristics of the fast transient potassium current of neurones where
      roles in shaping action potential duration and frequency have been proposed.
      Although acinar cells do not carry action potentials, our experiments indicate
      that the primary regulator of the current in these cells is the membrane
      potential. In whole-cell patch-clamped cells we demonstrate an outward current
      activated by depolarization. This current was transient and inactivated over the
      duration of the pulse (100-500 ms). The decay of the inactivation was adequately
      fitted by a single exponential. The time constant of decay, tau, at a membrane
      potential of +20 mV was 34 +/- 0.6 ms (mean +/- SEM, n = 6) and decreased with
      more positive pulse potentials. The steady-state inactivation kinetics showed
      that depolarized holding potentials reduced the amplitude of the current observed
      with a half-maximal inactivation at a membrane potential of -40.6 +/- 0.33 mV
      (mean +/- SEM, n = 5). These activation and inactivation characteristics were not
      affected by low intracellular calcium (10(-10) mol.l-1) or by an increase in
      calcium (up to 180 nmol.l-1). In addition we found no effect on the current of
      dibutyryl cyclic adenosine monophosphate (db-cAMP) or the agonist acetylcholine.
      The current was blocked by 4-aminopyridine (Kd approximately 0.5 mmol.l-1) but
      not affected by 10 mmol.l-1 tetraethylammonium.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7816552
TI  - A novel two-compartment culture dish allows microscopic evaluation of two
      different treatments in one cell culture simultaneously. Influence of external pH
      on Na+/Ca2+ exchanger activity in cultured rat cardiomyocytes.
AB  - A new type of culture dish containing two separate compartments is described,
      that can be used in high-magnification microscopy. Using the dish, two halves of
      a single-cell culture, grown on a standard coverslip, can be exposed to different
      treatments simultaneously, allowing the effect of one treatment to be compared
      with that of the other treatment in the same culture. This way, the natural
      variability that might exist between different individual cultures is
      circumvented. In addition, by simultaneously conducting two experiments per dish,
      the number of experiments needed can be decreased. This both reduces the time to
      complete a series of experiments and allows the optimal use of specimens that are
      difficult to obtain, such as human material. We found there is an excellent
      barrier between the two compartments for lipophilic and hydrophilic compounds,
      and for low-molecular-mass cations. To illustrate the use of the dish we describe
      the influence of external pH on the activity of the Na+/Ca2+ exchanger in intact
      cultured neonatal rat ventricular cardiomyocytes. The intracellular free calcium
      concentration ([Ca2+]i) in the cardiomyocytes, measured using fura-2 and imaging
      fluorescence microscopy, was studied during sodium-free incubation. The resulting
      rise in [Ca2+]i at pH 7.4 in one compartment was compared with that in the other
      compartment in which the pH was either 6.0, 7.0, 7.4 or 8.0. It was found that
      below pH 7.4, Na+/Ca2+ exchanger activity was diminished, whereas at pH higher
      than 7.4 the Na+/Ca2+ exchanger activity was increased.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7816553
TI  - Granulosa cells have calcium-dependent action potentials and a calcium-dependent
      chloride conductance.
AB  - We have found chicken granulosa cells to be excitable. Experiments using the
      whole-cell patch-clamp technique showed that they had membrane resting potentials
      of -62 +/- 3 mV (n = 8) and generated action potentials, either in response to 10
      ms depolarizing current pulses or, on occasion, spontaneously. The action
      potentials persisted in a Na(+)-free bath and were reversibly blocked by 4 mM
      Co2+. They lasted 0.9-3.0s with 64 mM Cl- in the pipette, were shortened 67 +/-
      8% by the Cl- channel blocker 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB;
      20 microM), and lengthened to 8.7 +/- 2.2 when the Cl- equilibrium potential
      (Vcl) was changed from -20 mV to -2 mV by using 134 mM Cl- in the pipette. With
      conventional whole-cell voltage-clamp, slowly activating and inactivating
      currents, which reached maximum amplitude after 0.35-1.40 s, were evoked by
      depolarizing voltage steps. These slow currents activated between voltage steps
      of -60 mV and -50 mV and reached a maximum inward amplitude at about -40 mV.
      Changing the Cl- concentration in the pipette (VCl of -2MV or -20 mV) or bath
      (VCl of -2 mV or + 18 mV) shifted their reversal potential in a direction
      consistent with a Cl- electrode. They were inhibited by the Cl- channel
      antagonists 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS; 0.5 mM),
      NPPB (20 microM), and 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid
      (SITS; 0.5 mM). The slow currents were blocked by Ca2+ deprivation, or by CO2+ (4
      mM), or by replacing external Ca2+ with Ba2+.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7816554
TI  - Chemical modification of squid axon K+ channel -SH groups with the organic
      mercurial compound p-hydroxymercuriphenylsulfonic acid (PHMPS).
AB  - In internally dialyzed voltage-clamped squid axons, intracellular or
      extracellular addition of the sulfhydryl group (-SH) specific reagent p
      hydroxymercuriphenylsulfonic acid (PHMPS), causes major modifications in the
      magnitude and kinetic parameters of the delayed rectifier K+ current. PHMPS
      produces a dramatic slow-down of the macroscopic current activation kinetics with
      a simultaneous reduction in its amplitude. In addition, it causes a marked
      increase in the delay of the macroscopic current at various pre-pulse potentials
      (Cole-Moore shift). The main effect of PHMPS at the single channel level is a
      sharp decrease in the open probability (4- to 5-fold). There is, however, a small
      reduction in single channel conductance (20%). Gating current experiments
      indicate that PHMPS causes a reduction in the voltage dependence of the
      activation process as well as a shift of the charge/voltage relationship towards
      more positive potentials. This, together with an increase in the mean open time,
      suggests that the open state has been destabilized. The results indicate that the
      reaction of -SH groups with PHMPS differentially affects the gating process. All
      the above mentioned effects are partially reversed by either dithiotreitol or
      beta-mercaptoethanol, -SH group reducing agents.

PMID- 7816555
TI  - Role of the cytoskeleton in the regulation of Cl- channels in human embryonic
      skeletal muscle cells.
AB  - The effects of volume change and cytoskeleton manipulation on the Cl- channels in
      human embryonic skeletal muscle cells were studied. Trypsination, used for
      production of myoballs, changes the channel properties only a little. When the
      external osmolarity was reduced from 300 to 270 mosmol/l, the specific Cl-
      conductance, gCl, (at -80 mV) of myoballs increased from 5.1 +/- 1.9 to 30.4 +/-
      12.2 microS/cm2 (SD; n = 6) within 15 min. Concomitantly, the kinetics of Cl-
      currents, elicited by clamping the membrane potential from a negative to positive
      values, changed from activation and subsequent slow inactivation to instantaneous
      activation with fast inactivation. G protein activation, protein kinase action or
      [Ca2+]i elevation seemed not to be involved in these effects. Similar changes
      were produced in the absence of a transmembrane osmotic gradient by 500 nM
      intracellular cytochalasin D (gCl = 34.3 +/- 10.3 microS/cm2; n = 6) or 12.5
      microM colchicine (gCl = 15.4 +/- 1.4 microS/cm2; n = 5). When the external
      osmolarity was increased to 418 mosmol/l, 1 microM cytochalasin D did not affect
      gCl. In four of six cell-attached patches the open probability of the
      intermediate Cl- channel was increased after reduction of the bath osmolarity. In
      inside-out patches, the drugs increased the open probability of the channels. It
      is concluded that the Cl- channels are under control of the cytoskeleton.

PMID- 7816556
TI  - Exercise-induced necrotic muscle damage and enzyme release in the four days
      following prolonged submaximal running in rats.
AB  - Male Wistar rats were made to run uphill on a treadmill 5.5 degrees incline at 17
      m min-1 for 4 h, and killed for muscle and serum sampling 2, 4, 12, 24, 48 or 96
      h after the exertion. To estimate the degree of muscle damage, beta-glucuronidase
      activity, total protein concentration, water content and morphology were examined
      in the red parts of quadriceps femoris (MQF) and soleus (MS) muscles, the distal
      white part of the rectus femoris muscle (MRF) and the superficial part of triceps
      brachii muscle (MTB). Simultaneous serum samples were assayed for creatine kinase
      (CK) activity and carbonic anhydrase III (CA III) concentration. Fibre swelling
      and interstitial oedema were detected in MS at 4 h and in MQF at 12 h and typical
      histopathological changes, including inflammation and fibre necrosis, in both
      muscles 12-96 h post-exertion. beta-Glucuronidase activity, a quantitative marker
      of muscle damage, was increased in MS at 4 h, in MQF at 24 h and in MRF 48 h
      after the running. No increase occurred in MTB. Water and protein content
      increased or decreased respectively, faster in MS (2 h post-exercise) than in MQF
      (12 h) or MRF (12 h). Water content thus contributed to muscle damage by
      preceding the increase in beta-glucuronidase activity. Serum CK activity was
      increased 2, 4, and 48 h after the running. Changes in serum CA III concentration
      were rather similar to those in CK but were not significant.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7816557
TI  - Basic fibroblast growth factor (bFGF) contributes to the enlargement of brown
      adipose tissue during cold acclimation.
AB  - The contribution of basic fibroblast growth factor to brown adipose tissue (BAT)
      enlargement during cold acclimation was investigated using rat brown adipocytes
      in primary culture. After cold exposure (at 5 degrees C) for 28 days, the level
      of bFGF messenger ribonucleic acid (mRNA) in BAT of cold-acclimated rats was
      markedly increased with the increase in the BAT weight. In addition, the blood
      plasma from cold-acclimated rats considerably enhanced the expression of basic
      fibroblast growth factor mRNA in rat brown adipocytes. Likewise, the blood plasma
      from cold-acclimated rats significantly stimulated the growth of rat brown
      adipocyte precursor cells compared with that from warm-acclimated rats, whereas
      there was no difference of effect between the two blood plasmas on the growth of
      bovine capillary endothelial cells. Basic fibroblast growth factor, but not
      platelet-derived growth factor stimulated the growth of brown adipocyte precursor
      cells. The conditioned medium from brown adipocyte primary culture markedly
      stimulated the growth of bovine capillary endothelial cells and the effect was
      inhibited considerably by antibasic fibroblast growth factor antibody. These
      results suggest that some factors concerned with the growth of brown adipocyte
      precursor cells are present in the blood plasma from cold-acclimated rats, and
      that basic fibroblast growth factor produced by brown adipocytes may
      significantly contribute to BAT enlargement by autocrine mechanisms during cold
      exposure.

PMID- 7816558
TI  - Effects of adenosine on Ca2+ transients and tension in aequorin-injected ferret
      papillary muscles.
AB  - The effects of adenosine on Ca2+ transients and tension in ferret papillary
      muscles were investigated using the aequorin method. Adenosine (0.01-1 mM)
      reduced the peak of Ca2+ transients and caused a slight concentration-dependent
      decrease in tension. Adenosine prolonged the decay time of Ca2+ transients but
      did not alter the time course of tension. In isoproterenol (0.1 microM)-treated
      preparations, adenosine decreased the peak of Ca2+ transients but did not alter
      the peak of tension. Adenosine prolonged the isoproterenol-shortened decay time
      of Ca2+ transients. The effects of adenosine on Ca2+ transients were antagonized
      by the selective A1 receptor antagonist 8-cyclopentyl-1,3,-dipropylxanthine. In
      the presence of isoproterenol, adenosine (0.1 mM) shifted the intracellular
      [Ca2+]/tension relation to the left. These results can be explained by the
      hypothesis that adenosine inhibits the activity of adenylate cyclase via
      stimulation of the A1 receptor, other mechanisms however cannot be overlooked.
      The prolongation of the decay time of Ca2+ transients and the increase in the
      Ca2+ sensitivity of the contractile elements are the underlying mechanisms of
      adenosine which maintain developed tension in twitch response, although adenosine
      decreases the peak of Ca2+ transients.

PMID- 7816559
TI  - Volume-activated Cl- currents in different mammalian non-excitable cell types.
AB  - The existence and properties of volume-activated Cl- currents were studied in 15
      different cell types (endothelium: human umbilical vein, human aorta, bovine
      pulmonary artery; fibroblasts: Swiss 3T3, L, C3H 10T1/2 and COS-1; epithelium:
      KB3, HeLa and A6; blood cells: RBL-2H3 and Jurkat; endothelioma cells derived
      from both subcutaneous and thymic hemangiomas; skin: IGR1 melanoma). Volume
      activated Cl- currents with common characteristics, i.e. small conductance,
      outward rectification, higher permeability for iodide than for chloride and
      sensitivity to block by 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB) could
      be elicited in all cells. The block of this current by tamoxifen and
      dideoxyforskolin is different for the various cell types, as well as the time
      course and the amplitude of the responses induced by repetitive applications of
      hypotonicity. Volume-activated Cl- channels with similar biophysical properties
      are therefore wide-spread among mammalian cells. This may reflect either a single
      Cl- channel that is ubiquitously expressed or a family of functionally related Cl
      channels with cell specific expression patterns.

PMID- 7816560
TI  - Properties of voltage-gated K+ currents expressed in Xenopus oocytes by mKv1.1,
      mKv1.2 and their heteromultimers as revealed by mutagenesis of the dendrotoxin
      binding site in mKv1.1.
AB  - Two similar mouse Shaker-like K+ channel genes, mKv1.1 and mKv1.2, have been
      shown to form heteromultimers in vivo. The predicted amino acid sequence of each
      channel is nearly identical in mice, rats and humans, suggesting that each has
      been highly conserved evolutionarily. Here we report the biophysical and
      pharmacological properties of each channel when expressed alone or when
      coexpressed in Xenopus oocytes. The voltage sensitivities of activation were
      similar for both, but the voltages at which the K+ conductances were half-maximal
      (V1/2) were -37 mV and -27 mV for mKv1.1 and mKv1.2 respectively. Both displayed
      voltage-dependent, but incomplete, inactivation following a prepulse with mKv1.2
      showing the greater degree of inactivation. For mKv1.1, the onset and recovery
      from inactivation could be described by single, slow time constants (2-4 s),
      whereas for mKv1.2 the onset and recovery from inactivation displayed a second,
      faster time constant (< 400 ms). Using a mutant mKv1.1 that is 100-fold less
      sensitive to dendrotoxin-I than mKv1.1, we demonstrate that this mutant mKv1.1
      and wild-type mKv1.2 subunits can form heteromultimeric channels. With some
      exceptions, of unknown significance, the biophysical properties of the
      heteromultimeric channels formed by wild-type mKv1.1 and mKv1.2 subunits were
      intermediate between those of mKv1.1 and mKv1.2 homomultimers, but quantitatively
      more similar to the more abundant subunit.

PMID- 7816561
TI  - Selective regulation of epithelial gene expression in rabbit Peyer's patch
      tissue.
AB  - The physiological mechanisms that regulate epithelial gene expression during
      enterocyte migration and differentiation are still poorly understood. The present
      study has used a combination of quantitative in situ hybridisation,
      immunohistochemistry and enzyme cytochemistry to examine epithelial cell
      differentiation in rabbit small intestine. We have measured and compared the
      levels of mRNA and enzyme activity of the enterocyte brush border markers
      alkaline phosphatase, amino-peptidase N and lactase in normal villus epithelia
      and in epithelial cells exposed directly to the Peyer's patch immune environment.
      All three genes appeared to be expressed in parallel, but in each epithelial
      population examined, the pattern of gene expression was different. The level of
      these mRNAs was markedly reduced in Peyer's patch-associated epithelia, this
      being most pronounced in the follicle-associated epithelium, compared with normal
      villi. The activities of alkaline phosphatase and aminopeptidase N approximated
      the expression of their genes, whereas additional post-transcriptional events
      were shown to clearly contribute to the level of lactase activity in these
      tissues. These findings demonstrate that the reduced brush border hydrolase
      activity in Peyer's patch tissue that has been observed previously, is due to a
      down-regulation of epithelial gene expression in this location. These
      observations have been used to discuss epithelial differentiation in Peyer's
      patch tissue and the possible role of local immune factors in regulating such
      events.

PMID- 7816562
TI  - Modification of sodium channel gating and kinetics by versutoxin from the
      Australian funnel-web spider Hadronyche versuta.
AB  - The effects of a neurotoxin (versutoxin VTX), purified from the venom of the
      Australian Blue Mountains funnel-web spider Hadronyche versuta, on the ionic
      currents in rat dorsal root ganglion cells were investigated under voltage-clamp
      conditions using the whole-cell patch-clamp technique. VTX had no effect on
      tetrodotoxin-resistant (TTX-R) sodium currents or potassium currents. In contrast
      VTX produced a dose-dependent slowing or removal of tetrodotoxin-sensitive (TTX
      S) sodium current inactivation, a reduction in peak TTX-S sodium current but did
      not markedly slow tail current kinetics of TTX-S sodium currents. This steady
      state sodium current was maintained during prolonged depolarizations at all test
      potentials and the reduction in sodium current amplitude produced by VTX had an
      apparent Ki of 37 nM. In the presence of 32 nM VTX the voltage dependence of
      steady-state sodium channel inactivation (h infinity) also showed a significant 7
      mV shift in the voltage midpoint in the hyperpolarizing direction, with no change
      in the slope factor. In addition there was a steady-state or non-inactivating
      component present (14 +/- 2% of maximal sodium current) at prepulse potentials
      more depolarized than -40 mV, potentials which normally inactivate all TTX-S
      sodium channels. Finally, there was an observed increase in the rate of recovery
      from inactivation in the presence of VTX. These selective actions of VTX on
      sodium channel gating and kinetics are similar to those of alpha-scorpion and sea
      anemone toxins.

PMID- 7816563
TI  - Role of vasopressin V2 receptors in modulation of the renal cortico-papillary
      NaCl gradient.
AB  - In order to examine if modulation by vasopressin of NaCl transport in Henle's
      loops (via V2 receptors) can significantly modify medullary ionic hypertonicity,
      the effects of stimulation or inhibition of these receptors were studied in
      anaesthetized Wistar rats. Total electrolyte concentration in the medullary
      interstitium was continuously measured as tissue admittance (reciprocal
      impedance), using needle electrodes recording from the inner and outer medulla of
      the in situ kidney. Deamino-[Cys1, D-Arg8]vasopressin (dDAVP], a V2 agonist,
      infused i.v. at 7.5 ng.min-1.kg-1, significantly increased admittance by 9% and
      8% in the inner and outer medulla, respectively. A slightly pressor i.v. infusion
      of natural arginine vasopressin (AVP) induced pressure natriuresis and did not
      affect medullary electrolyte concentration. Inhibition of V2 receptors with
      [d(CH2)5, D-Phe2, Ile4]-AVP, infused i.v. at 133 micrograms.h-1 kg-1 in
      indomethacin-treated rats, decreased admittance (significant in the inner
      medulla). Neither of the three agents used caused significant changes in the
      renal blood flow (RBF) or clearance of inulin (Cin). The demonstration that
      changing activity of V2 receptors affects the corticopapillary NaCl gradient
      indicates that, at least in rodents, stimulation of loop salt transport by AVP
      may represent an additional mechanism enhancing urine concentration.

PMID- 7816564
TI  - Propagation of excitation-contraction coupling into ventricular myocytes.
AB  - This paper examines the [Ca2+]i transient in isolated rat heart cells using a
      laser scanning confocal microscope and the calcium indicator fluo-3. We find that
      the depolarization-evoked [Ca2+]i transient is activated synchronously near the
      surface and in the middle of the heart cell with similar kinetics of activation.
      The time of rise of the transient did not depend on whether the sarcoplasmic
      reticulum (SR) Ca-release was abolished (by thapsigargin and ryanodine). The
      synchrony of activation and the similarity of levels of [Ca2+]i at the peripheral
      and deeper myoplasm (regardless of the availability of SR Ca-release) shows that
      sarcolemmal Ca channels and SR Ca-release channels are distributed throughout the
      rat heart cell and that the propagation of the action potential into the interior
      of the cell is rapid. In addition, the activation of calcium release from the SR
      by CICR is rapid (<< 2 ms) when compared to the time-course of calcium influx via
      the sarcolemmal Ca channel.

PMID- 7816565
TI  - Practical guidance for testing the accuracy of deconvolution results from quantal
      analysis.
AB  - A Monte Carlo study was carried out to test the reliability of the Maximum
      Likelihood Estimator (MLE) approach for quantal analysis. This widely used
      statistical method was applied to extract a finite mixture of Gaussian
      distributions from simulated data. The data were generated by convolving a
      distribution of discrete amplitude steps (multiples of a unitary step Q) with
      Gaussian noise of various standard deviations (sigma n). Our results offer
      practical guidance on when to use the MLE, taking into account the determining
      parameters: signal to noise ratio (Q/sigma n, the most important parameter),
      number of samples collected and the number of components (k). For a given set of
      parameters the algorithm always converged to the "true" values, never converged
      to the "true" values or converged in only a fraction of cases to the "true"
      values. The behavior of the fitting routine in the parameter space is displayed
      in contour plots. These contour plots can be used as a guide to test the accuracy
      of deconvolution results.

PMID- 7816566
TI  - Level of expression in Xenopus oocytes affects some characteristics of a plant
      inward-rectifying voltage-gated K+ channel.
AB  - The plant K+ channel KAT1 shows some similarity to animal voltage-gated channels
      of the Shaker superfamily. Contrary to these animal counterparts, this plant
      channel is inwardly rectifying, being gated upon hyperpolarization. Different
      levels of expression of KAT1 in Xenopus oocytes could be obtained by increasing
      the amount of injected cRNA. The resulting KAT1 gating and sensitivity to
      external caesium were significantly changed. Similar findings have been published
      regarding animal voltage-gated channels. The present data show that plant
      channels may also undergo modification of their activity upon modification of
      their level of expression.

PMID- 7816567
TI  - The evolution of a caring-based program.

PMID- 7816568
TI  - Creating a caring environment for nursing education.

PMID- 7816570
TI  - Courses in curriculum.

PMID- 7816569
TI  - Prizing, valuing, and growing in a caring-based program.

PMID- 7816571
TI  - Undergraduate program: purpose and objectives.

PMID- 7816572
TI  - Graduate program: purpose and objectives.

PMID- 7816573
TI  - Nursing: a discipline of knowledge grounded in caring.

PMID- 7816574
TI  - The shared study of nursing.

PMID- 7816575
TI  - The experience of struggle, freedom, and growth.
AB  - The philosophy contains both constraints and freedoms. Loss of the minority view
      was expressed as a struggle. Molding to fit the dominant view led to a sense of
      connectedness. Individuals living within the faculty circle sought both to
      maintain their own views and to recognize and support the needs of the group.
      From this struggle, feelings of freedom and growth emerged, as well as respect
      and support for others. Nevertheless, at the point in time captured by this
      study, respect for individuals was easier to achieve than respect for the
      diversity of ideas. In truth, these cannot be separated, and so the struggle to
      understand and live the philosophy is an ongoing process.

PMID- 7816576
TI  - The experience of being a student in a caring-based program.

PMID- 7816578
TI  - The relationship of quality in long-term care to nursing education.

PMID- 7816577
TI  - Researching experiences of living caring.

PMID- 7816579
TI  - Minimum competencies of nursing staff in LTC facilities.

PMID- 7816580
TI  - A vision for nursing education reform.
AB  - Significant changes in nursing education are needed if the profession is to
      deliver on the promise embedded in Nursing's Agenda for Health Care Reform. In
      the past, nursing's focus on community-based care was philosophical for the many
      and actual only for the few who chose to specialize. Now, however, the Agenda for
      Health Care Reform is being advanced as nursing's alternative vision for health
      care delivery, and community-based care is increasingly the generalist's rather
      than the specialist's domain. Preparing all graduates of nursing education
      programs for community-based care, therefore, becomes the responsibility of all
      programs and all faculty. Perhaps in varying degrees, but a commonly shared
      responsibility, nonetheless.

PMID- 7816581
TI  - Issues facing faculty in long-term care.

PMID- 7816582
TI  - Educational advancement for quality in long-term care.

PMID- 7816583
TI  - Education articulation models and the nursing home industry.

PMID- 7816584
TI  - Policy and funding implications of programs providing education in long-term care
      institutions.

PMID- 7816585
TI  - Competencies of the baccalaureate and higher degree nursing graduate.

PMID- 7816586
TI  - Health as expanding consciousness.

PMID- 7816587
TI  - The nicotine transdermal patch: use in the dental office tobacco cessation
      program.

PMID- 7816588
TI  - The Pankey-Mann-Schuyler philosophy of restorative dentistry: an overview.

PMID- 7816589
TI  - Young dentists, new choices.

PMID- 7816590
TI  - Mission accomplished: dentistry for Nepal.

PMID- 7816591
TI  - Charitable giving for dentists.

PMID- 7816592
TI  - Winning the battle against overhead.

PMID- 7816593
TI  - The Hyperbaric Medicine Facility at Hennepin County Medical Center.

PMID- 7816594
TI  - Prevention of osteoradionecrosis: a case report.

PMID- 7816595
TI  - Family politics: an interview with Drs. John and Ben Clayburgh. Interview by J.A.
      Anderson.

PMID- 7816596
TI  - Dental office overhead: a review of the statistics and a model for their
      application.

PMID- 7816597
TI  - The lifetime of a patient.

PMID- 7816598
TI  - Should you buy or lease your next business car?

PMID- 7816600
TI  - Predicting internal exons by oligonucleotide composition and discriminant
      analysis of spliceable open reading frames.
AB  - A new method which predicts internal exon sequences in human DNA has been
      developed. The method is based on a splice site prediction algorithm that uses
      the linear discriminant function to combine information about significant triplet
      frequencies of various functional parts of splice site regions and preferences of
      oligonucleotides in protein coding and intron regions. The accuracy of our splice
      site recognition function is 97% for donor splice sites and 96% for acceptor
      splice sites. For exon prediction, we combine in a discriminant function the
      characteristics describing the 5'-intron region, donor splice site, coding
      region, acceptor splice site and 3'-intron region for each open reading frame
      flanked by GT and AG base pairs. The accuracy of precise internal exon
      recognition on a test set of 451 exon and 246693 pseudoexon sequences is 77% with
      a specificity of 79%. The recognition quality computed at the level of individual
      nucleotides is 89% for exon sequences and 98% for intron sequences. This
      corresponds to a correlation coefficient for exon prediction of 0.87. The
      precision of this approach is better than other methods and has been tested on a
      larger data set. We have also developed a means for predicting exon-exon
      junctions in cDNA sequences, which can be useful for selecting optimal PCR
      primers.

PMID- 7816599
TI  - An analysis of genes regulated by the multi-functional transcriptional regulator
      Yin Yang-1.

PMID- 7816601
TI  - Direct analysis of native and chimeric GATA specific DNA binding proteins from
      Aspergillus nidulans.
AB  - In Aspergillus nidulans the regulatory gene areA is responsible for mediating
      nitrogen metabolite repression. The areA product (AREA) represents an example of
      the GATA family of DNA binding proteins, which are characterised by the presence
      of a GATA domain consisting of a zinc finger within a highly conserved region of
      52 amino acids. Among the other transcription factors included in this family is
      the principal erythroid transcription factor, GATA-1, which contains two GATA
      domains. In order to demonstrate high specificity binding of native AREA to DNA
      containing the sequence -GATA-, and investigate the presence in A.nidulans of
      other proteins with related specificities, we have used gel mobility shift
      assays. Both AREA-dependent and independent complexes have been identified. Two
      strains bearing chimeric genes were also characterised. In these, the region
      encoding the native GATA domain of AREA was replaced by sequences from murine
      GATA-1 cDNA encoding either the equivalent C-terminal domain or both the N and C
      terminal domains. Strains bearing the areA::NC-GATA construct, which includes the
      sequence encoding both the N and C-terminal domains of GATA-1, leads to a
      pronounced increase in one of two AREA-dependent complexes and implicates the N
      terminal domain of GATA-1 in mediating protein-protein interactions.

PMID- 7816602
TI  - Phosphorylation of the c-Fos and c-Jun HOB1 motif stimulates its activation
      capacity.
AB  - The c-Fos and c-Jun proteins bind an AP1 site and activate transcription
      synergistically. These two proteins have a common activation domain which has two
      co-operating motifs, HOB1 and HOB2. The HOB1 motif of c-Jun includes S73 which is
      required for Ha-Ras-induced super-activation and phosphorylation by MAP kinase
      like enzymes. Since c-Fos HOB1 has a conserved Thr residue (T232) analogous to c
      Jun S73 we have proposed that c-Fos HOB1 will be regulated in the same way as c
      Jun HOB1. Here we show that the HOB1-containing activation domain of c-Fos is
      stimulated by Ha-Ras in vivo and phosphorylated by a MAP kinase family member in
      vitro and that mutating T232 to Ala abolishes both functions. Collectively these
      results suggest that phosphorylation of the HOB1 motif increases its activation
      capacity. To provide direct evidence for this we change the context of c-Fos T232
      to a PKA recognition site, and show that HOB1 activity is now stimulated by the
      catalytic subunit of PKA. This 'PKA specificity' experiment represents a novel
      and powerful way to analyse phosphorylation events involved in a variety of
      biological functions.

PMID- 7816603
TI  - Family A and family B DNA polymerases are structurally related: evolutionary
      implications.
AB  - In order to establish the evolutionary relationship between the family A and B
      DNA polymerases, we have closely compared the 3'-->5' exonuclease domains between
      the Klenow fragment of E.coli DNA polymerase I (a family A DNA polymerase) and
      the bacteriophage PRD1 DNA polymerase, the smallest member of the DNA polymerase
      family B. Although the PRD1 DNA polymerase has a smaller 3'-->5' exonuclease
      domain, its active sites appear to be very similar to those of the Klenow
      fragment. Site-directed mutagenesis studies revealed that the residues important
      for the 3'-->5' exonuclease activity, particularly metal binding ligands for the
      Klenow fragment, are all conserved in the PRD1 DNA polymerase as well. The metal
      binding ligands are also essential for the strand-displacement activity of the
      PRD1 DNA polymerase. Based on these results and the studies by others in various
      systems, we conclude that family A and B DNA polymerases, at least in the 3'-->5'
      exonuclease domain, are structurally as well as evolutionarily related.

PMID- 7816604
TI  - Two separate sites contribute to AP-1 activation of the promoter for 3-hydroxy-3
      methylglutaryl coenzyme A synthase.
AB  - Metabolic flux into the mevalonate pathway is regulated by end product repression
      and cell growth. In the experiments reported here the transcriptional promoter
      for an early enzyme of the pathway, 3-hydroxy-3-methylglutaryl coenzyme A
      synthase, is shown to be activated by the growth stimulatory agent tetraphorbol
      acetate (TPA). We show that TPA has a direct stimulatory action on the promoter
      and further that this is mediated by the AP-1 transcription factor. In addition,
      we show that there are two separate cis-acting sites that bind AP-1 and both are
      required for maximal stimulation. We further show that in AP-1-deficient cells
      ectopic expression of AP-1 stimulates synthetic promoters containing two copies
      of each synthase element upstream of a minimal promoter. The physiological
      rationale of having both end product repression and direct activation by growth
      stimulatory cues is discussed.

PMID- 7816605
TI  - The interaction between the first and last intron nucleotides in the second step
      of pre-mRNA splicing is independent of other conserved intron nucleotides.
AB  - Virtually all pre-mRNA introns begin with the sequence /GU and end with AG/
      (where / indicates a border between an exon and an intron). We have previously
      shown that the G residues at the first and last positions of the yeast actin
      intron interact during the second step of splicing. In this work, we ask if other
      highly conserved intron nucleotides also take part in this /G-G/ interaction. Of
      special interest is the penultimate intron nucleotide (AG/), which is important
      for the second step of splicing and is in proximity to other conserved intron
      nucleotides. Therefore, we tested interactions of the penultimate intron
      nucleotide with the second intron nucleotide (/GU) and with the branch site
      nucleotide. We also tested two models that predict interactions between sets of
      three conserved intron nucleotides. In addition, we used random mutagenesis and
      genetic selection to search for interactions between nucleotides in the pre-mRNA.
      We find no evidence for other interactions between intron nucleotides besides the
      interaction between the first and last intron nucleotides.

PMID- 7816606
TI  - Molecular characterisation of plant U14 small nucleolar RNA genes: closely linked
      genes are transcribed as polycistronic U14 transcripts.
AB  - U14snoRNAs are highly conserved eukaryotic nucleolar small RNAs involved in
      precursor ribosomal RNA processing. In vertebrates, U14snoRNAs and a number of
      other snoRNAs are transcribed within introns of protein coding genes and are
      released by processing. We have isolated potato and maize genomic U14 clones
      using PCR-amplified plant U14 probes. Plant U14s show extensive homology to those
      from yeast and animals but contain plant-specific sequences. One of the isolated
      maize clones contains a cluster of four U14 genes in a region of only 761 bp,
      confirming the close linkage of U14 genes in maize, potato and barley as
      established by PCR. The absence of known plant promoter elements, the proximity
      of the genes and the detection of transcripts containing linked U14s by RT-PCR
      indicates that some plant U14snoRNAs are transcribed as precursor RNAs which are
      then processed to release individual U14s. Whether plant U14snoRNAs are intron
      encoded or transcribed from novel promoter sequences, remains to be established.

PMID- 7816607
TI  - Studies of bacteriophage P2 DNA replication: localization of the cleavage site of
      the A protein.
AB  - Bacteriophage P2 replicates via a modified rolling circle-type of mechanism,
      where the P2 A protein acts as an initiator of the replication by inducing a
      single-stranded cut at the origin of replication (ori). The exact location of the
      cut induced by the A protein in vivo is determined in this report by: (i)
      restriction analysis; (ii) DNA sequence analysis; and (iii) primer extensions. It
      is located 89.2% from the left end of the P2 genome, which is within the coding
      part of the A gene, in a region devoid of secondary structures. The A gene has
      been cloned into an expression vector, and the A protein has been purified. The
      purified A protein does not bind to double-stranded ori containing DNA, but it
      cleaves single-stranded ori containing DNA, which indicates that a special DNA
      structure and/or protein is required to make the ori accessible for the A
      protein.

PMID- 7816608
TI  - Identification of a novel family of human endogenous retroviruses and
      characterization of one family member, HERV-K(C4), located in the complement C4
      gene cluster.
AB  - We have identified a novel family of about 10-50 human endogenous retrovirus
      elements (HERVs) and have characterized one family member (HERV-KC4). This
      retrovirus element is integrated within intron 9 of and complement C4A genes and
      also in some C4B genes, and is a principal contribution to interlocus and
      interallelic length heterogeneity of C4 genes. The HERV-K(C4) sequence has a
      typical retrovirus structure with elements of gag, pol and env domains, flanked
      by two long terminal repeats (LTRs) and is similar to type A, B and D
      retroviruses. Multiple termination codons preclude the existence of long open
      reading frames, suggesting that the HERV-K(C4) sequence is no longer functional.
      Zoo blot hybridization reveals that New World monkeys appear to lack sequences
      similar to HERV-K(C4), suggesting that integration has occurred after the
      divergence of Old and New World monkeys. Retrotransposition of prototype viruses
      is presumed to have led to the amplification and integration of the members of
      the family in different loci, which in humans, appear to be dispersed over
      several chromosomes. The absence of the HERV-K(C4) element in some C4B genes in
      both humans and orangutangs indicate that the retrovirus inserted into the C4A
      gene after the duplication of the cluster. Subsequent spread of the HERV-K(C4)
      sequence to C4B genes presumably occurred by interlocus sequence exchange
      mechanisms, such as unequal crossover and gene conversion-like mechanisms.

PMID- 7816609
TI  - Electron microscopy mapping of oligopurine tracts in duplex DNA by peptide
      nucleic acid targeting.
AB  - Biotinylated homopyrimidine decamer peptide nucleic acids (PNAs) are shown to
      form sequence-specific and stable complexes with complementary oligopurine
      targets in linear double-stranded DNA. The noncovalent complexes are visualized
      by electron microscopy (EM) without chemical fixation using streptavidin as an EM
      marker. The triplex stoichiometry of the PNA-DNA complexes (two PNA molecules
      presumably binding by Watson-Crick and Hoogsteen pairing with one of the strands
      of the duplex DNA) is indicated by the appearance of two streptavidin 'beads' per
      target site in some micrographs, and is also supported by the formation of two
      retardation bands in a gel shift assay. Quantitative analysis of the positions of
      the streptavidin 'beads' revealed that under optimized conditions PNA-DNA
      complexes are preferably formed with the fully complementary target. An increase
      in either the PNA concentration or the incubation time leads to binding at sites
      containing one or two mismatches. Our results demonstrate that biotinylated PNAs
      can be used for EM mapping of short targets in duplex DNA.

PMID- 7816610
TI  - Splicing factor SF3a60 is the mammalian homologue of PRP9 of S.cerevisiae: the
      conserved zinc finger-like motif is functionally exchangeable in vivo.
AB  - A cDNA encoding the 60 kDa subunit of mammalian splicing factor SF3a has been
      isolated. The deduced protein sequence reveals a 30% identity to the PRP9
      splicing protein of the yeast S.cerevisiae. The highest homology is present in a
      zinc finger-like region in the C-terminal domain of both proteins. The PRP9 zinc
      finger-like motif has been replaced by the equivalent region of mammalian SF3a60.
      The chimeric protein rescues the temperature-sensitive phenotype of the prp9-1
      mutant strain demonstrating that not only the structure but also the function of
      this domain has been conserved during evolution.

PMID- 7816612
TI  - Daunomycin modifies the sequence-selective recognition of DNA by actinomycin.
AB  - The antitumour antibiotic actinomycin D normally binds to DNA by intercalation at
      sequences containing the CpG step, but in the presence of daunomycin it has been
      reported to interact with poly(dA-dT). This observation has neither been
      confirmed nor explained. Here we have used a photoreactive 7-azido derivative of
      actinomycin to study the effect of daunomycin on its binding to three DNA
      fragments. Daunomycin did indeed alter the binding of actinomycin to the DNA,
      such that the antibiotic was displaced from its primary GpC sites onto secondary
      sites in the DNA, though not to AT regions especially. These findings suggest a
      possible scientific explanation for the increased toxicity seen during
      combination chemotherapy with these two drugs.

PMID- 7816611
TI  - Early dissociation of nuclear factor I from the origin during initiation of
      adenovirus DNA replication studied by origin immobilization.
AB  - The DNA-binding domain of Nuclear Factor I (NFIBD) enhances initiation of
      adenovirus DNA replication up to 50-fold by binding to the auxiliary region of
      the origin and positioning the viral DNA polymerase. To study if and when NFIBD
      dissociates from the template, we immobilized origin DNA to glutathione-agarose
      beads by means of a GST-NFIBD fusion protein. This immobilized template is active
      in replication. By analyzing the release of prelabeled templates from the beads
      under different conditions, we show that NFIBD dissociates already early during
      initiation. During preinitiation NFIBD remains bound, but as soon as dCTP, dATP
      or dTTP are added, efficient dissociation occurs. A much lower dissociation level
      was induced by addition of dGTP. Since dCTP, dATP and dTTP are required for
      formation of a pTP-CAT initiation intermediate, we explain our results by
      conformational changes occurring in the polymerase during initiation leading to
      disruption of both the interaction between the polymerase and NFI as well as the
      interaction between NFI and the DNA.

PMID- 7816613
TI  - Purification and characterization of human ribonuclease HII.
AB  - A ribonuclease H activity from human placenta has been separated by ion exchange
      chromatography from the major RNase HI enzyme. Additional chromatographic steps
      allowed further purification, more than 3,000 fold compared to the crude extract
      in which it represents about 15% of the total RNase H activity. The enzyme
      requires Mg2+ ions for its activity, is strongly inhibited by the addition of
      Mn2+ ions or other divalent transition metal ions, and exhibits a pH optimum
      between 8.5 and 9. It shows a strong sensitivity to the SH-blocking agent N
      ethylmaleimide. It has a strict specificity for double-stranded RNA-DNA duplexes
      and exhibits neither single-stranded nor double-stranded RNase (or DNase)
      activities. Therefore, this enzyme displays the characteristics of class II RNase
      H and is now termed RNase HII. Renaturation gel assays and gel filtration
      experiments proved a monomeric structure for the active enzyme with a native
      molecular weight of about 33 kDa. The human RNase HII acts as an endonuclease and
      releases oligoribonucleotides with 3'-OH and 5'-phosphate ends. It is therefore a
      candidate for the RNase H-mediated effect of antisense oligodeoxynucleotides.

PMID- 7816615
TI  - Re-replication of SV40 minichromosomes is inhibited at the stage of chain
      elongation.
AB  - The template activities of protein-free SV40 DNA and SV40 minichromosomes for DNA
      re-replication are compared in in vitro replication assays. Density substitution
      experiments and two-dimensional gel electrophoresis show that protein-free DNA
      can replicate for at least two cycles whereas salt-treated minichromosomes
      replicate only once. Re-replication of minichromosomes is blocked at the stage of
      replicative chain elongation suggesting that replicatively assembled chromatin
      has structural features that prevent a second round of replication.

PMID- 7816614
TI  - Intron-less RNA injected into the nucleus of Xenopus oocytes accesses a regulated
      translation control pathway.
AB  - The translation of a capped, polyadenylated RNA after injection into the nucleus
      of Xenopus oocytes occurs only if the RNA contains an intron. A single point
      mutation in the splice donor site prevents translation. Intron-less RNA is
      exported efficiently to the cytoplasm and is held, undegraded, in a
      translationally inert state for several days. Translation can be activated by
      treating the oocytes with progesterone or by injecting antibodies that bind the
      FRGY2 class of messenger RNA binding proteins, p56 and p60, but these antibodies
      are only effective if delivered to the nucleus. Inhibitors of casein kinase II
      also activate translation whereas phosphatase inhibitors block progesterone
      mediated activation of translation. These data suggest the presence of an RNA
      handling pathway in the nucleus of Xenopus oocytes which is regulated by casein
      kinase type II phosphorylation and which directs transcripts to be sequestered by
      p56/p60 or by closely related proteins. This pathway can be bypassed if the RNA
      contains an intron and it can be reversed by progesterone treatment. These data
      may have implications for understanding translational control during early
      development.

PMID- 7816616
TI  - The influence of imperfectly paired helices I and III on the catalytic activity
      of hammerhead ribozymes.
AB  - Several catalytic antisense RNAs directed against different regions of the
      genomic or antigenomic RNA of Sendai virus were constructed. All RNAs contained
      the same catalytic domain based on hammerhead ribozymes but some had deletions or
      mutations resulting in imperfect helices I and III. Pre-annealed
      substrate/ribozyme complexes were used to determine the rates of the cleavage
      process for the different ribozymes under single-turnover conditions. It was
      found that the sequence context surrounding the cleavable motif influenced the
      cleavage efficiencies. Deletions or mutations of nucleotides 2.1 or 15.1 and 15.2
      according to the numbering system for hammerhead ribozymes of Hertel et al.
      destroyed catalytic activity. Deletions of nucleotide 2.2 or additional
      nucleotides in the helix I-forming region of the ribozyme did not destruct, but
      only reduced the cleavage efficiencies. Similar results were observed for a
      deletion of nucleotide 15.3. Simultaneous deletions within helices I and III
      resulted in alternative cleavage sites. The potential consequences for the
      specificity of the ribozyme reaction are discussed.

PMID- 7816617
TI  - Hac1: a novel yeast bZIP protein binding to the CRE motif is a multicopy
      suppressor for cdc10 mutant of Schizosaccharomyces pombe.
AB  - We cloned by phenotypic complementation a novel Saccharomyces cerevisiae's
      multicopy suppressor of the Schizosaccharomyces pombe cdc10-129 mutant which we
      call HAC1, an acronym of 'homologous to ATF/CREB 1'. It encodes a bZIP (basic
      leucine zipper) protein of 230 amino acids with close homology to the mammalian
      ATF/CREB transcription factor and gel-retardation assays showed that it binds
      specifically to the CRE motif. HAC1 is not essential for viability. However, the
      hac1 disruptant becomes caffeine sensitive, which is suppressed by multicopy
      expression of the yeast PDE2 (Phosphodiesterase 2) gene. Although the mRNA level
      of HAC1 is almost constitutive throughout the cell cycle, it fluctuates during
      meiosis. The upstream region of the HAC1 gene contains a T4C site, a URS
      (upstream repression sequence) and a TR (T-rich) box-like sequence, which reside
      upstream of many meiotic genes. These results suggest that HAC1 may also be one
      of the meiotic genes.

PMID- 7816618
TI  - Identification of two mismatch-binding activities in protein extracts of
      Schizosaccharomyces pombe.
AB  - We have performed band-shift assays to identify mismatch-binding proteins in cell
      extracts of Schizosaccharomyces pombe. By testing heteroduplex DNA containing
      either a T/G or a C/C mismatch, two distinct band shifts were produced in the
      gels. A low mobility complex was observed with the T/G substrate, while a high
      mobility complex was present with C/C. Further analysis of the mismatch-binding
      specificities revealed that the T/G binding activity also binds to T/C, C/T, T/T,
      T/-, A/-, C/-, G/-, G/G, A/A, A/C, A/G, G/T, G/A, and C/A substrates with varying
      efficiencies, but not binds to C/C. The C/C binding activity efficiently binds to
      C/C, T/C, C/T, C/A, A/C, C/-, and weakly also to T/T, while all other mispairs
      are not recognized. Protein extracts of a mutant strain, defective in the mutS
      homologue swi4, displayed both mismatch-binding activities. Thus, swi4 does not
      encode for either one of the mismatch-binding proteins.

PMID- 7816619
TI  - Cloning of cDNAs from Arabidopsis thaliana that encode putative protein
      phosphatase 2C and a human Dr1-like protein by transformation of a fission yeast
      mutant.
AB  - We characterized three Arabidopsis thaliana cDNA clones that could rescue the
      sterile phenotype of the Schizosaccharomyces pombe pde1 mutant, which is
      defective in cAMP phosphodiesterase. The first clone had a coding capacity of 399
      amino acids that is 35% identical with rat protein phosphatase 2C (PP2C). The
      second had a coding capacity of 159 amino acids that is 41% identical with human
      Dr1. Dr1 has been shown to interact with TATA-binding protein (TBP) and block its
      ability to activate transcription. The third encoded Arabidopsis TBP itself.
      Saccharomyces cerevisiae TBP also could suppress the sterile phenotype if
      expressed in S.pombe pde1 cells, but overexpression of S.pombe TBP could do so
      very poorly. These observations suggest preliminarily that PP2C may counteract
      cAMP-dependent protein kinase in fission yeast cells, and that the heterologous
      TBPs and Dr1 may interfere with the general transcription factors of S.pombe so
      that the gene expression in the host cell becomes affirmative of sexual
      development. Furthermore, the identification of a Dr1-like protein in A.thaliana
      strongly argues for the ubiquity of this protein among eukaryotic genera and for
      a conserved mechanism to regulate transcription initiation that involves Dr1.

PMID- 7816620
TI  - Evolutionarily conserved elements in the 5' untranslated region of beta globin
      mRNA mediate site-specific priming of a unique hairpin structure during cDNA
      synthesis.
AB  - Generation of double-stranded cDNA during reverse transcription of a variety of
      mRNA molecules is well known to involve the formation of covalently linked
      antisense and sense strands in a hairpin configuration. In the present study we
      have examined the sequence of molecular events which occurs during cDNA synthesis
      from mouse beta globin mRNA, in particular the self-priming event that initiates
      synthesis of sense-strand DNA. Upon completion of reverse transcription of globin
      mRNA and the removal of RNA template by RNase H activity associated with reverse
      transcriptase, the 3' end of cDNA snaps back to form a stable double-stranded
      structure, which is extended by reverse transcriptase to generate the sense DNA
      strand. Surprisingly, the fourteen 3' terminal nucleotides of the beta globin
      antisense DNA strand (cDNA) have strong complementarity with an internal segment
      of the same molecule corresponding to a portion of the 5'-untranslated region of
      the mRNA located just upstream of the translation start site. Efficient second
      strand cDNA synthesis appears to require the occurrence within the cDNA molecule
      of these two complementary elements, one of which must be 3'-terminal. A second
      surprising feature is that the strong complementarity between the terminal and
      the internal portions of the molecule exists in the antisense DNA and not in the
      sense mRNA strand. This is because A:C mismatches on the sense strand correspond
      to relatively stable T:G base pairs on the antisense strand. Such an extended
      region of complementarity within the segment of cDNA corresponding to the short
      5' untranslated region of beta globin mRNA is unlikely to occur purely by chance,
      suggesting some underlying function. In this regard it is of interest that cDNAs
      of adult beta globin mRNAs from other mammalian species show a very similar
      arrangement of complementary elements, and that complementarity is heavily
      conserved, even when there are substitutions in nucleotide sequence.

PMID- 7816621
TI  - RAP1 stimulates single- to double-strand association of yeast telomeric DNA:
      implications for telomere-telomere interactions.
AB  - Repressor Activator Protein 1 (RAP1) of Saccharomyces cerevisiae is an abundant
      nuclear protein implicated in telomere length maintenance, transactivation, and
      in the establishment of silent chromatin domains. The RAP1 binding site 5' of the
      yeast HIS4 gene is also a region of hyperrecombination in meiosis. We report here
      that as RAP1 binds its recognition consensus, it appears to untwist double
      stranded DNA, which we detect as the introduction of a negative supercoil in
      circularization assays. Coincident with the RAP1-dependent untwisting, we observe
      stimulation of the association of a single-stranded yeast telomeric sequence with
      its homologous double-stranded sequence in a supercoiled plasmid. This unusual
      distortion of the DNA double helix by RAP1 may contribute to the RAP1-dependent
      enhancement of recombination rates and promote non-duplex strand interactions at
      telomeres.

PMID- 7816622
TI  - Suppression of mutations in the core of the Tetrahymena ribozyme by spermidine,
      ethanol and by substrate stabilization.
AB  - We have previously described a collection of mutations in conserved residues of
      the core of the Tetrahymena self-splicing intron. Most of these single base
      substitutions have less than 10% of the activity of their parental intron
      derivative [Couture, S., et al., (1990) J. Mol. Biol., 215, 345-358]. We examined
      the effect of two agents known to stabilize RNA structure, spermidine and
      ethanol, on the activity of many of these mutant RNAs. In the presence of either
      5 mM spermidine or 20% ethanol most substitution mutations were partially or
      completely suppressed. These conditions also increased the temperature optima of
      both wild-type and mutant ribozymes. In addition, we find that mutations are also
      suppressed by a high concentration of GTP, a substrate in the reaction which is
      bound specifically by the intron. Thus we observe a general suppression of
      mutations in an RNA enzyme (ribozyme) by spermidine, ethanol and by substrate
      stabilization. These results are consistent with the idea that most mutations
      destabilize the folded structure of the ribozyme and can be suppressed by any of
      a variety of stabilizing influences.

PMID- 7816623
TI  - The yeast BDF1 gene encodes a transcription factor involved in the expression of
      a broad class of genes including snRNAs.
AB  - While screening for genes that affect the synthesis of yeast snRNPs, we
      identified a thermosensitive mutant that abolishes the production of a reporter
      snRNA at the non-permissive temperature. This mutant defines a new gene, named
      BDF1. In a bdf1-1 strain, the reporter snRNA synthesized before the temperature
      shift remains stable at the non-permissive temperature. This demonstrates that
      the BDF1 gene affects the synthesis rather than the stability of the reporter
      snRNA and suggests that the BDF1 gene encodes a transcription factor. BDF1 is
      present in single copy on yeast chromosome XII, and is important for normal
      vegetative growth but not essential for cell viability. bdf1 null mutants share
      common phenotypes with several mutants affecting general transcription and are
      defective in snRNA production. BDF1 encodes a protein of 687 amino-acids
      containing two copies of the bromodomain, a motif also present in other
      transcription factors as well as a new conserved domain, the ET domain, also
      present in Drosophila and human proteins.

PMID- 7816624
TI  - Regulation of EcoRII methyltransferase: effect of mutations on gene expression
      and in vitro binding to the promoter region.
AB  - EcoRII Methyltransferase (M.EcoRII) which methylates the second C in the sequence
      CCWGG (W = A/T) is autogenously regulated by binding to the 5' regulatory region
      of its gene. DNase I footprinting experiments demonstrated that purified M.EcoRII
      protected a 47-49 bp region of DNA immediately upstream of the ecoRIIM coding
      region. We have studied this interaction with mutants of the enzyme, in vitro by
      DNA binding and in vivo by investigating the repression in trans of expression of
      beta-galactosidase from an ecoRIIM-lacZ operon fusion. Two catalytically active
      mutants failed to repress expression of the fusion whereas catalytically inactive
      mutants had repressor activity. However, with one of the catalytically inactive
      mutants, C186S, in which the catalytic Cys was replaced with Ser, and which bound
      unmethylated CCWGG sequences, repression could only be demonstrated when those
      sequences in cellular DNA were methylated by supplying a cloned dcm gene in
      trans. In vitro binding of the DNA fragment containing the ecoRIIM regulatory
      region was detected only with the mutants that showed repressor activity,
      including C186S. Results indicate that down-regulation of the gene in vivo and
      binding to the promoter in vitro are not dependent on the catalytic properties of
      M.EcoRII. Mobility shift experiments with C186S also revealed that it could bind
      either the promoter or unmethylated CCWGG sites, but not both. We conclude that
      the concentration of unmethylated CCWGG sites controls expression from the
      ecoRIIM promoter.

PMID- 7816625
TI  - The CpG-specific methylase SssI has topoisomerase activity in the presence of
      Mg2+.
AB  - A prokaryotic CpG-specific methylase from Spiroplasma, SssI methylase, is now
      widely used to study the effect of CpG methylation in mammalian cells, and can
      processively modify cytosines in CpG dinucleotides in the absence of Mg2+. In the
      presence of Mg2+, we found (i) that the methylation reaction is distributive
      rather than processive as a result of the decreased affinity of SssI methylase
      for DNA, and (ii) that a type I-like topoisomerase activity is present in SssI
      methylase preparations. This topoisomerase activity was still present in SssI
      methylase further purified by either SDS-polyacrylamide or isoelectric focusing
      gel electrophoresis. We show that methylase and topoisomerase activities are not
      functionally interdependent, since conditions exist where only one or the other
      enzymatic activity is detectable. The catalytic domains of SssI methylase and
      prokaryotic topoisomerases show similarity at the amino acid level, further
      supporting the idea that the topoisomerase activity is a genuine activity of SssI
      methylase. Mycoplasmas, including Spiroplasma, have the smallest genomes of all
      living organisms; thus, this condensation of two enzymatic activities into the
      same protein may be a result of genome economy, and may also have functional
      implications for the mechanism of methylation.

PMID- 7816626
TI  - Requirements for noncovalent binding of vaccinia topoisomerase I to duplex DNA.
AB  - Vaccinia DNA topoisomerase binds duplex DNA and forms a covalent adduct at sites
      containing a conserved sequence element 5'(C/T)CCTT decreases in the scissile
      strand. Distinctive aspects of noncovalent versus covalent interaction emerge
      from analysis of the binding properties of Topo(Phe-274), a mutated protein which
      is unable to cleave DNA, but which binds DNA noncovalently. Whereas DNA cleavage
      by wild type enzyme is most efficient with 'suicide' substrates containing fewer
      than 10 base pairs distal to the scissile bond, optimal noncovalent binding by
      Topo(Phe-274) requires at least 10-bp of DNA 3' of the cleavage site. Thus, the
      region of DNA flanking the pentamer motif serves to stabilize the noncovalent
      topoisomerase-DNA complex. This result is consistent with the downstream
      dimensions of the DNA binding site deduced from nuclease footprinting. Topo(Phe
      274) binds to duplex DNA lacking the consensus pentamer with 7-10-fold lower
      affinity than to CCCTT-containing DNA.

PMID- 7816627
TI  - Rapid pulsed field separation of DNA molecules up to 250 kb.
AB  - Pulsed field gel electrophoresis (PFGE) is capable of resolving a wide size range
      of DNA molecules which would all co-migrate in conventional agarose gels. We
      describe pulsed field gel conditions which permit DNA fragments of up to 250
      kilobases (kb) to be separated in only 3.5 h. The separations, which employ
      commercially available gel boxes, are achieved using conditions which deviate
      significantly from traditional pulsed field conditions. PFGE separations have
      been thought to require reorientation angles greater than 90 degrees to be
      effective. However, reorientation angles of 90 degrees and even less will resolve
      DNA fragments a few hundred kb and smaller approximately 5 x faster than with
      standard pulsed field conditions. The mobility of DNA fragments separated with 90
      degrees reorientation angles is switch time-dependent, as is seen for DNA run
      with the commonly used reorientation angle of 120 degrees. With DNA fragments of
      several hundred kb and smaller, higher field strengths may be used, resulting in
      still greater increases in separation speed. The conditions described allow DNA
      from large insert bacterial clones, such as those using cosmid, Fosmid, P1,
      bacterial artificial chromosome (BAC), or P1-derived artificial chromosome (PAC)
      vectors, to be prepared, digested and analyzed on gels within a single working
      day.

PMID- 7816628
TI  - Interactions of DNA binding ligands with PNA-DNA hybrids.
AB  - The interactions of two representative mixed-sequence (one with an AT-stretch)
      PNA-DNA duplexes (10 or 15 base-pairs) and a PNA2/DNA triplex with the DNA
      binding reagents distamycin A, 4',6-diamidino-2-phenylindole (DAPI), ethidium
      bromide, 8-methoxy-psoralen and the delta and lambda enantiomers of Ru(phen)2
      dppz2+ have been investigated using optical spectroscopic methods. The behaviour
      of these reagents versus two PNA-PNA duplexes has also been investigated. With
      triple helical poly(dA)/(H-T10-Lys-NH2)2 no significant intercalative binding was
      detected for any of the DNA intercalators, whereas DAPI, a DNA minor groove
      binder, was found to exhibit a circular dichroism with a positive sign and
      amplitude consistent with minor groove binding. Similarly, a PNA-DNA duplex
      containing a central AATA motif, a typical minor groove binding site for the DNA
      minor groove binders distamycin A and DAPI, showed binding for both of these
      drugs, though with strongly reduced affinity. No important interactions were
      found for any of the ligands with a PNA-DNA duplex consisting of a ten base-pair
      mixed purine-pyrimidine sequence with only two AT base-pairs in the centre. Nor
      did any of the ligands show any detectable binding to the PNA-PNA duplexes (one
      containing an AATT motif). Various PNA derivatives with extentions of the
      backbone, believed to increase the flexibility of the duplex to opening of an
      intercalation slot, were tested for intercalation of ethidium bromide or 8
      methoxypsoralen into the mixed sequence PNA-DNA duplex, however, without any
      observation of improved binding. The importance of the ionic contribution of the
      deoxyribose phosphate backbone, versus interactions with the nucleobases, for
      drug binding to DNA is discussed in the light of these findings.

PMID- 7816629
TI  - Initiation zone of DNA replication at the aldolase B locus encompasses
      transcription promoter region.
AB  - Aldolase A (AldB) gene is one of the liver-specific genes, which is activated in
      the fetal stage. As a first step to investigate the functional relationship
      between transcription and DNA replication, we intended to determine the
      initiation zone of replication nearest to the AldB gene region. BrdU-labeled
      nascent DNA was obtained from G1/S arrested hepatoma cells at various times after
      entering S phase. Hybridization of the newly synthesized, BrdU-labeled DNA with
      probes corresponding to regions spanning about 26 Kb, revealed that replication
      zone locates within the AldB gene region. This result, together with the result
      of hybridization of nascent DNA obtained by alkaline sucrose density-gradient
      centrifugation, suggested that the initiation zone is located within a more
      defined region (about 1.0 Kb) containing AldB promoter. In the predicted
      initiation zone, a purine-rich element which shows high homology to known
      mammalian origin sequences and other replication components are found. Further,
      autonomously replicating activity of this initiation zone was examined by DNA
      transfection. The results showed that the predicted initiation zone confers
      replication initiation in Cos-1 cells.

PMID- 7816630
TI  - High frequency vector-mediated transformation and gene replacement in
      Tetrahymena.
AB  - Recently, we developed a mass DNA-mediated transformation technique for the
      ciliated protozoan Tetrahymena thermophila that introduces transforming DNA by
      electroporation into conjugating cells. Other studies demonstrated that a
      neomycin resistance gene flanked by Tetrahymena H4-I gene regulatory sequences
      transformed Tetrahymena by homologous recombination within the H4-I locus when
      microinjected into the macronucleus. We describe the use of conjugant
      electrotransformation (CET) for gene replacement and for the development of new
      independently replicating vectors and a gene cassette that can be used as a
      selectable marker in gene knockout experiments. Using CET, the neomycin
      resistance gene flanked by H4-I sequences transformed Tetrahymena, resulting in
      the replacement of the H4-I gene or integrative recombination of the H4-I/neo/H4
      I gene (but not vector sequences) in the 5' or 3' flanking region of the H4-I
      locus. Gene replacement was obtained with non-digested plasmid DNA but releasing
      the insert increased the frequency of replacement events about 6-fold. The
      efficiency of transformation by the H4-I/neo/H4-I selectable marker was unchanged
      when a single copy of the Tetrahymena rDNA replication origin was included on the
      transforming plasmid. However, the efficiency of transformation using CET
      increased greatly when a tandem repeat of the replication origin fragment was
      used. This high frequency of transformation enabled mapping of the region
      required for H4-I promoter function to within 333 bp upstream of the initiator
      ATG. Similarly approximately 300 bp of sequence downstream of the translation
      terminator TGA of the beta-tubulin 2 (BTU2) gene could substitute for the 3'
      region of the H4-I gene. This hybrid H4-I/neo/BTU2 gene did not transform
      Tetrahymena when subcloned on a plasmid lacking an origin of replication, but did
      transform at high frequency on a two origin plasmid. Thus, the H4-I/neo/BTU2
      cassette is a selectable marker that can be used for gene knockout in
      Tetrahymena. As a first step toward constructing a vector suitable for cloning
      genes by complementation of mutations in Tetrahymena, we also demonstrated that
      the vector containing 2 origins and the H4-I/neo/BTU2 cassette can co-express a
      gene encoding a cycloheximide resistant ribosomal protein.

PMID- 7816631
TI  - Alternate pathways for processing in the internal transcribed spacer 1 in pre
      rRNA of Saccharomyces cerevisiae.
AB  - We have extended the system of Nogi et al. (Proc. Natl. Acad. Sci. USA 88, 1991,
      3962-3966) for transcription of rRNA from an RNA polymerase II promoter in
      strains lacking functional RNA polymerase I. In our strains two differentially
      marked rRNA transcription units can be expressed alternately. Using this system
      we have shown that the A2 processing site in the internal transcribed spacer 1
      (ITS1) of the pre-rRNA is dispensable. According to the accepted processing
      scheme, the A2 site serves to separate the parts of the primary rRNA transcript
      that are destined for incorporation into the two ribosomal subunits. However, we
      have found that, when A2 is impaired, separation of the small and large subunit
      rRNAs occurs at a processing site further downstream in ITS1, indicating that
      alternate pathways for ITS1 processing exist. Short deletions in the A2 region
      still allow residual processing at the A2 site. Mapping of the cleavage sites in
      such deletion transcripts suggests that sequences downstream of the A2 site are
      used for determining the position of the cleavage.

PMID- 7816633
TI  - Oligonucleotides with novel, cationic backbone substituents:
      aminoethylphosphonates.
AB  - Oligonucleotide (2-aminoethyl)phosphonates in which the backbone consisted of
      isomerically pure, alternating (2-aminoethyl)-phosphonate and phosphodiester
      linkages have been prepared and characterized. One of these single isomer
      oligonucleotides (Rp) formed a more stable duplex with DNA or RNA than its
      corresponding natural counterpart. Hybrid stability was more pH-dependent, but
      less salt-dependent than a natural duplex. The specificity of hybridization was
      examined by hybridization of an oligonucleotide containing one (2
      aminoethyl)phosphonate to oligonucleotides possessing mismatches in the region
      opposite to the aminoethyl group. In contrast to oligonucleotides containing
      (aminomethyl)-phosphonate linkages, oligonucleotide (2-aminoethyl)phosphonates
      were completely stable to hydrolysis in aqueous solution. These oligonucleotides
      were resistant to nuclease activity but did not induce RNase H mediated cleavage
      of a complementary RNA strand. Incubation in a serum-containing medium resulted
      in minimal degradation over 24 hours. Studies of cell uptake by flow cytometry
      and confocal microscopy demonstrated temperature dependent uptake and
      intracellular localization. (2-Aminoethyl)phosphonates represent a novel approach
      to the introduction of positive charges into the backbone of oligonucleotides.

PMID- 7816632
TI  - Non-covalent DNA groove-binding by 2-amino-1-methyl-6-phenylimidazo[4,5
      b]pyridine.
AB  - The cooked meat mutagen 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP)
      is metabolized in vivo to electrophilic intermediates that covalently bind to DNA
      guanines. Here we address the mechanism of PhIP's non-covalent interaction with
      DNA by using spectroscopic and computational methodologies. NMR methodologies
      indicated that upon addition of DNA, PhIP aromatic protons underwent a small,
      0.11-0.12 p.p.m. upfield shift. DNA phosphorus resonances of non-covalent PhIP
      DNA complexes broadened and slightly shifted upfield, while DNA base imino proton
      resonances shifted slightly downfield relative to DNA alone. UV and fluorescence
      spectra of PhIP titrated with DNA showed no detectable shifting and hypochromism
      of absorbance or fluorescence bands. In the presence of DNA, PhIP fluorescence
      was efficiently quenched by acrylamide, but not by silver ion. Further, the NMR
      spectra suggest that PhIP is in fast exchange with the DNA, and is slightly
      specific for adenine-thymine (A-T) sequences. Finally, structural arguments based
      on quantum chemistry calculations suggested that PhIP and its metabolites are
      unlikely to intercalate into DNA. These data collectively indicate that PhIP non
      covalently binds in a groove of DNA.

PMID- 7816635
TI  - Elimination of endogenous aberrant kappa chain transcripts from sp2/0-derived
      hybridoma cells by specific ribozyme cleavage: utility in genetic therapy of HIV
      1 infections.
AB  - The pooled degenerate-primer polymerase chain reaction (PCR) technology is now
      widely used in the amplification and cloning of murine hybridoma-specific
      immunoglobulin gene cDNAs. The design of primers is mainly based on the highly
      conserved 5' terminus of immunoglobulin gene variable regions and the constant
      region in the 3' terminus. Of note, most murine hybridoma cell lines are derived
      from the Sp2/0 cell line, which is demonstrated to express endogenous aberrant
      kappa chains (abV kappa). This high-level endogenous abV kappa mixes with
      specific kappa chains in the hybridomas and interferes with the efficiency of the
      reverse transcriptase (RT)-PCR cloning strategy. In this report, during the
      cloning of murine anti-human immunodeficiency virus type I (HIV-1) hybridoma
      immunoglobulin cDNAs, a specific primer-PCR screening system was developed, based
      on the abV kappa complementarity-defining region (CDR), to eliminate abV kappa
      carrying plasmids. Furthermore, an abV kappa sequence-specific derived ribozyme
      was developed and packaged in a retroviral expression vector system. This abV
      kappa ribozyme can be transduced into different murine hybridomas, and expressed
      intracellularly to potently eliminate endogenous abV kappa RNA.

PMID- 7816634
TI  - An AP1 binding site upstream of the kappa immunoglobulin intron enhancer binds
      inducible factors and contributes to expression.
AB  - Expression of the kappa immunoglobulin light chain gene requires developmental-
      and tissue-specific regulation by trans-acting factors which interact with two
      distinct enhancer elements. A new protein-DNA interaction has been identified
      upstream of the intron enhancer, within the matrix-associated region of the J-C
      intron. The binding activity is greatly inducible in pre-B cells by bacterial
      lipopolysaccharide and interleukin-1 but specific complexes are found at all
      stages of B cell development tested. The footprinted binding site is homologous
      to the consensus AP1 motif. The protein components of this complex are
      specifically competed by an AP1 consensus motif and were shown by supershift to
      include c-Jun and c-Fos, suggesting that this binding site is an AP1 motif and
      that the Jun and Fos families of transcription factors play a role in the
      regulation of the kappa light chain gene. Mutation of the AP1 motif in the
      context of the intron enhancer was shown to decrease enhancer-mediated activation
      of the promoter in both pre-B cells induced with LPS and constitutive expression
      in mature B cells.

PMID- 7816636
TI  - Enhanced resistance to nuclease degradation of nucleic acids complexed to
      asialoglycoprotein-polylysine carriers.
AB  - We have previously shown targeting of DNA to hepatocytes using an
      asialoorosomucoid-polylysine (AsOR-PL) carrier system. The AsOR-PL conjugate
      condenses DNA and facilitates entry via specific receptor-ligand interactions. In
      these studies, our objective was to determine if AsOR-PL conjugates protect bound
      DNA from nuclease attack. Double-stranded plasmid or single-stranded
      oligonucleotide DNA, alone or bound to conjugate, was incubated under conditions
      mimicking those encountered during in vitro and in vivo transfections. The
      results showed that complexed DNA was effectively protected from degradation by
      serum nucleases. Degradation of single-stranded oligonucleotides was inhibited 3-
      to 6-fold in serum during 5 hours of incubation. For complexed plasmids, greater
      than 90% remained full-length during 1.5 and 3 hour incubations in serum or
      culture medium containing 10% serum, respectively. Uncomplexed plasmid was
      completely degraded after 15 minutes in serum or 60 minutes in medium. In cell
      lysates, the conjugate was not effective in inhibiting endonuclease activity;
      plasmids were readily converted from supercoiled to open circular and linear
      forms. However, the resultant nicked forms were substantially protected from
      further degradation during one hour of incubation compared to plasmid alone.
      Under all conditions complexed DNA did not readily dissociate from the conjugate.
      Overall, for both single and double-stranded DNA, AsOR-PL conjugates conferred
      substantial protection from nuclease degradation.

PMID- 7816637
TI  - Structural properties of the [d(G3T4G3)]2 quadruplex: evidence for sequential syn
      syn deoxyguanosines.
AB  - Two-dimensional 1H NMR studies on the dimeric hairpin quadruplex formed by
      d(G3T4G3) in the presence of either NaCl or KCl are presented. In the presence of
      either salt, the quadruplex structure is characterized by half the guanine
      nucleosides in the syn conformation about the glycosidic bond, the other half in
      the anti conformation, as reported for other similar sequences. However, 1H NOESY
      and 1H-31P heteronuclear correlation experiments demonstrate that the
      deoxyguanosines do not strictly alternate between syn and anti along individual
      strands. Thus we find the following sequences with regard to glycosidic bond
      conformation: 5'-G1SG2SG3AT4AT5A-T6AT7AG8SG9AG10A-3' and 5'-G11SG12AG13AT14AT1
      5AT16AT17AG18SG19SG20A-3', where S and A denote syn and anti, respectively. This
      represents the first experimental evidence for a nucleic acid structure
      containing two sequential nucleosides in the syn conformation. The stacking
      interactions of the resulting quadruplex quartets and their component bases have
      been evaluated using unrestrained molecular dynamics calculations and energy
      component analysis. These calculations suggest that the sequential syn-syn/anti
      anti and syn-anti quartet stacks are almost equal in energy, whereas the anti-syn
      stack, which is not present in our structure, is energetically less favorable by
      about 4 kcal/mol. Possible reasons for this energy difference and its
      implications for the stability of quadruplex structures are discussed.

PMID- 7816638
TI  - Direct fluorescence analysis of genetic polymorphisms by hybridization with
      oligonucleotide arrays on glass supports.
AB  - A simple and rapid method for the analysis of genetic polymorphisms has been
      developed using allele-specific oligonucleotide arrays bound to glass supports.
      Allele-specific oligonucleotides are covalently immobilized on glass slides in
      arrays of 3 mm spots. Genomic DNA is amplified by PCR using one fluorescently
      tagged primer oligonucleotide and one biotinylated primer oligonucleotide. The
      two complementary DNA strands are separated, the fluorescently tagged strand is
      hybridized to the support-bound oligonucleotide array, and the hybridization
      pattern is detected by fluorescence scanning. Multiple polymorphisms present in
      the PCR product may be detected in parallel. The effect of spacer length, surface
      density and hybridization conditions were evaluated, as was the relative efficacy
      of hybridization with single or double-stranded PCR products. The utility of the
      method was demonstrated in the parallel analysis of 5 point mutations from exon 4
      of the human tyrosinase gene.

PMID- 7816639
TI  - Crystal structure of the highly distorted chimeric decamer
      r(C)d(CGGCGCCG)r(G).spermine complex--spermine binding to phosphate only and
      minor groove tertiary base-pairing.
AB  - The crystal structure of the self-complementary chimeric decamer duplex
      r(C)d(CGGCGCCG)r(G), with RNA base pairs at both termini, has been solved at 1.9
      A resolution by the molecular replacement method and refined to an R value of
      0.145 for 2,314 reflections. The C3'-endo sugar puckers of the terminal riboses
      apparently drive the entire chimeric duplex into an A-DNA conformation, in
      contrast to the B-DNA conformation adopted by the all-deoxy decamer of the same
      sequence. Five symmetry related duplexes encapsulate a spermine molecule which
      interacts with ten phosphate groups, both directly and through water molecules to
      form multiple ionic and hydrogen bonding interactions. The spermine interaction
      severely bends the duplexes by 31 degrees into the major groove at the fourth
      base pair G(4).C(17), jolts it and slides the 'base plate' into the minor groove.
      This base pair, together with the adjacent base pair in the top half and the
      corresponding pseudo two-fold related base pairs in the bottom half, form four
      minor groove base-paired multiples with the terminal base pairs of two
      neighboring duplexes.

PMID- 7816640
TI  - Isolation and developmental expression of a rat cDNA encoding a cysteine-rich
      zinc finger protein.
AB  - A number of cysteine-rich proteins have recently been isolated by homology
      screening, differential library screens, and association with other proteins. In
      this report, we describe the isolation of the rat cysteine-rich protein from a
      rat brain library during a search for clones with homology to the delta-opioid
      receptor. One of the cDNAs isolated hybridized to a 1.8 kb mRNA abundantly
      expressed throughout the rat brain as well as in rat liver. In situ hybridization
      reveals a wide distribution in rat brain; in particular, abundant hybridization
      was detected in the hippocampus, cerebellum, habenula, reticular thalamic nucleus
      and interposed nucleus. Nucleotide sequence analysis of a 1403 bp cDNA clone
      indicated 77% identity with the cDNA for human cysteine-rich protein (hCRP), that
      translates into a 99% identity at the amino acid level. The predicted amino acid
      sequence suggests four zinc fingers, two of the C4 class and two of the C2HC
      class. This structural motif is characteristic of members of the LIM domain
      protein family. The mRNA is serum-inducible in Balb/c 3T3 cells. Additional study
      suggests that its expression is not induced by either NGF treatment of PC12h
      pheochromocytoma cells, or inflammation-induced injury in the spinal cord at up
      to 60 min after injury. It does appear to be developmentally expressed in rat
      brain, consistent with a potential role in neuronal development. The rat CRP
      clone will be useful for studying the function of CRPs in rodent models.

PMID- 7816641
TI  - NMR investigation of Hoogsteen base pairing in quinoxaline antibiotic--DNA
      complexes: comparison of 2:1 echinomycin, triostin A and [N-MeCys3,N-MeCys7]
      TANDEM complexes with DNA oligonucleotides.
AB  - Hoogsteen base pairs have been demonstrated to occur in base pairs adjacent to
      the CpG binding sites in complexes of triostin A and echinomycin with a variety
      of DNA oligonucleotides. To understand the relationship of these unusual base
      pairs to the sequence specificity of these quinoxaline antibiotics, the
      conformation of the base pairs flanking the YpR binding sites of the 2:1 drug-DNA
      complexes of triostin A with [d(ACGTACGT)]2 and of the TpA specific [N-MeCys3, N
      MeCys7] TANDEM with [d(ATACGTAT)]2 have been studied by 1H NMR spectroscopy. In
      both the 2:1 triostin A-DNA complex and the 2:1 [N-MeCys3, N-MeCys7] TANDEM-DNA
      complex, the terminal A.T base pairs are Hoogsteen base paired with the 5'
      adenine in the syn conformation. This indicates that both TpA specific and CpG
      specific quinoxaline antibiotics are capable of inducing Hoogsteen base pairs in
      DNA. However, in both 2:1 complexes, Hoogsteen base pairing is limited to the
      terminal base pairs. In the 2:1 triostin A complex, the internal adenines are
      anti and in the 2:1 [N-MeCys3, N-MeCys7] TANDEM-DNA complex, the internal
      guanines are anti regardless of pH, which indicates that the central base pairs
      of both complexes form Watson-Crick base pairs. This indicates that the sequence
      dependent nature of Hoogsteen base pairing is the same in TpA specific and CpG
      specific quinoxaline antibiotic-DNA complexes. We have calculated a low
      resolution three-dimensional structure of the 2triostin A-[d(ACGTACGT)]2 complex
      and compared it with other CpG specific quinoxaline antibiotic-DNA complexes. The
      role of stacking in the formation of Hoogsteen base pairs in these complexes is
      discussed.

PMID- 7816642
TI  - Antisense pro-drugs: 5'-ester oligodeoxynucleotides.
AB  - Oligonucleotides bearing a terminal lipophilic group attached through a
      biodegradable ester bond should be useful as antisense pro-drugs with improved
      cellular uptake. The synthesis of 5'-ester oligonucleotides is, however,
      problematic due to lability of the ester bond during aqueous ammonia treatment
      that is commonly used for the deprotection of synthetic oligonucleotides. The
      synthesis of 5'-palmitoyl oligodeoxynucleotides was accomplished in good yield by
      the use of a combination of base-labile tert-butylphenoxyacetyl amino protecting
      groups (t-BPA), the oxalyl-CPG anchor group, and ethanolamine (EA) as a
      deprotecting reagent.

PMID- 7816643
TI  - Bending and curvature calculations in B-DNA.
AB  - A simple program, BEND, has been written to calculate the magnitude of local
      bending and macroscopic curvature at each point along an arbitrary B-DNA
      sequence, using any desired bending model that specifies values of twist, roll
      and tilt as a function of sequence. The program has been used to evaluate six
      different DNA bending models in three categories. Two are bent non-A-tract
      models: (a) A new model based on the nucleosome positioning data of Satchwell et
      al 1986 (J. Mol. Biol. 191, 659-675), (b) The model of Calladine et al 1988 (J.
      Mol. Biol. 201, 127-137). Three are bent A-tract models: (c) The wedge model of
      Bolshoy et al 1991 (Proc. Natl. Acad. Sci. USA 88, 2312-2316), (d) The model of
      Cacchione et al 1989 (Biochem. 28, 8706-8713), (e) A reversed version of model
      (b). The last is a junction model: (f) The model of Koo & Crothers 1988 (Proc.
      Natl. Acad. Sci. USA 85, 1763-1767). Although they have widely different
      assumptions and values for twist, roll and tilt, all six models correctly predict
      experimental A-tract curvature as measured by gel retardation and cyclization
      kinetics, but only the new nucleosome positioning model is successful in
      predicting curvature in regions containing phased GGGCCC sequences. This model-
      showing local bending at mixed sequence DNA, strong bends at the sequence GGC,
      and straight, rigid A-tracts--is the only model consistent with both solution
      data from gel retardation and cyclization kinetics and structural data from x-ray
      crystallography.

PMID- 7816644
TI  - Fast screening of mouse mutants generated after homologous recombination.

PMID- 7816645
TI  - A rapid and simple method for the isolation of apoptotic DNA fragments.

PMID- 7816647
TI  - Improved method of gene detection using exon amplification.

PMID- 7816646
TI  - Polymerase chain reaction products containing 5-methyldeoxycytidine: a microplate
      immunoquantitation method.

PMID- 7816648
TI  - Rapid PCR-based characterization of sequences flanking microsatellites in large
      insert libraries.

PMID- 7816649
TI  - M.phi 3TII: a new monospecific DNA (cytosine-C5) methyltransferase with
      pronounced amino acid sequence similarity to a family of adenine-N6-DNA
      methyltransferases.
AB  - The temperate B.subtilis phages phi 3T and rho 11s code, in addition to the
      multispecific DNA (cytosine-C5) methyltransferases (C5-MTases) M. phi 3TI and M.
      rho 11sI, which were previously characterized, for the identical monospecific C5
      MTases M. phi 3TII and M. rho 11sII. These enzymes modify the C of TCGA sites, a
      novel target specificity among C5-MTases. The primary sequence of M. phi 3TII
      (326 amino acids) shows all conserved motifs typical of the building plan of C5
      MTases. The degree of relatedness between M. phi 3TII and all other mono- or
      multispecific C5-MTases ranges from 30-40% amino acid identity. Particularly M.
      phi 3TII does not show pronounced similarity to M. phi 3TI indicating that both
      MTase genes were not generated from one another but were acquired independently
      by the phage. The amino terminal part of the M. phi 3TII (preceding the variable
      region 'V'), which predominantly constitutes the catalytic domain of the enzyme,
      exhibits pronounced sequence similarity to the amino termini of a family of A-N6
      MTases, which--like M.TaqI--recognize the general sequence TNNA. This suggests
      that recently described similarities in the general three dimensional
      organization of C5- and A-N6-MTases imply divergent evolution of these enzymes
      originating from a common molecular ancestor.

PMID- 7816651
TI  - Women's health and the acute myocardial infarction.

PMID- 7816650
TI  - Power: an elusive franchise.

PMID- 7816652
TI  - Nursing in Japan.

PMID- 7816653
TI  - Innovative approach to patient education.
AB  - Limitations on staff nurses' teaching skills, more acute conditions, more complex
      self-care treatments, and shorter hospitalizations--all hampered our efforts to
      educate patients before the implementation of our patient training program, the
      RSTC. Occasionally, the patients' learning needs have delayed discharge. But such
      delays are good for both the patient and the hospital, as inadequate patient
      education before discharge is thought to be the reason for visits to physician
      offices and emergency departments after discharge, and both constitute higher
      utilization costs for our facility. Ultimately, the design of our RSTC program
      satisfies the educational needs of our patients for self-care within the context
      of fiscal efficiency.

PMID- 7816655
TI  - Discipline-specific inquiry: the hermeneutics of theory-guided nursing research.
AB  - Gadamer's insights into the hermeneutical process contribute a great deal to the
      understanding that may accompany scientific inquiry, if preexisting prejudices
      are respected for their contribution to discipline-specific knowledge. Heidegger
      said that language "speaks for us in what has been spoken." This means that the
      way nurses use language signifies who they are as a group of health
      professionals. Language is the vehicle that discloses nurses' values and beliefs.
      Parse's theory is one framework among many that provides nurse researchers with a
      coherent language of the human-health interrelationship for guiding inquiry. The
      prejudices of the theory are clearly specified and they circumscribe unique
      arenas for knowledge development. The language of the theory describes human
      becoming from a nursing perspective. It is complex, process oriented, and
      abstract, just like the human-health phenomena it represents. It is precisely the
      unique understanding and knowledge of nursing theories that may direct further
      discipline-specific inquiry and structure activities for an autonomous nursing
      practice. Ultimately, knowledge generated from discipline-specific inquiry will
      expand theories for guiding creative and meaningful practice with persons,
      families, and groups that seek professional engagements.

PMID- 7816656
TI  - Review and synthesis of selected nursing studies on teaching empathy and
      implications for nursing research and education.
AB  - The mandate by caring theorists to integrate caring into nursing curricula could
      be accomplished without major curricula change. The integration of empathy
      training, with special emphasis on expanding one's awareness of self as well as
      others, espouses a pedagogical approach to caring. The continuing effort of nurse
      researchers and educators to clarify how to best teach empathy and to integrate
      heuristic methods into nursing education and practice settings is imperative to
      the essence of nursing--caring.

PMID- 7816654
TI  - For-profit entities and continuing education: a nursing perspective.

PMID- 7816657
TI  - Guest editorial: are people expendable?

PMID- 7816658
TI  - Transcultural care.

PMID- 7816659
TI  - Men in nursing.

PMID- 7816660
TI  - More on 'men'.

PMID- 7816661
TI  - More on 'men'.

PMID- 7816662
TI  - Professional development. Wound care: revision notes (continuing education
      credit).

PMID- 7816663
TI  - Worth their salt.

PMID- 7816664
TI  - Body politic. Choppy seas.

PMID- 7816665
TI  - Sexuality. Biased care?

PMID- 7816666
TI  - Sexuality. A sensitive question.

PMID- 7816667
TI  - Measuring renal function with urea and creatinine tests.
AB  - The second paper in our series on laboratory examination of specimens discusses
      the measurement of urea and creatinine in the blood as tests of renal function.
      It outlines the synthesis of urea and creatinine and their excretion following
      glomerular filtration.

PMID- 7816668
TI  - Long-term health problems and community care.
AB  - The development of comprehensive local community services is patchy. If people
      with mental health problems are to receive appropriate and effective care, the
      resources need to be distributed differently, coordinated more effectively and
      focused on those with severe and long-term problems.

PMID- 7816669
TI  - Mental health. Refocusing long-term care.
AB  - How to provide care in the community for clients who are suffering from a long
      term mental health problem is a dilemma for mental health service planners and
      providers. Community psychiatric nurses (CPNs) are the ideally placed profession
      to provide care for these people according to recent reports and are a part of
      the multidisciplinary teams. This paper outlines how four CPNs worked in a
      unidisciplinary team titled the community support teams (CST) in Greenwich,
      taking secondary referrals exclusively from the psychiatric service and each
      carrying a small caseload of severely ill clients. The client input of the CST is
      compared to the generic CPNs' input who provided a standard CPN service to a wide
      client mix including long-term clients.

PMID- 7816670
TI  - Special nutritional needs of surgical patients.
AB  - Hospital-induced malnutrition has long been recognised as a problem, particularly
      as the very group of people who find themselves in a hospital for treatment,
      whether for long- or relatively short-term treatment are, almost by definition,
      at risk. This paper seeks to identify the causes of treatment induced
      malnutrition and discusses methods that can be successfully used to overcome this
      avoidable condition.

PMID- 7816671
TI  - Primary care nursing. Community nursing practice management and teamwork.
AB  - The government has announced that GP fundholding is to be extended to include a
      'community fundholding' option. In the new scheme, all GPs will be eligible to
      become community fundholders and buy community nursing services from NHS
      community trusts. This paper outlines what the National Health Service Executive
      guidelines will mean for community nurses working in GP practices and describes
      four models, currently up and running, of new primary health-care team nursing
      practice management and teamwork.

PMID- 7816673
TI  - Nursing abroad. Back to the future.

PMID- 7816672
TI  - Network for strength.

PMID- 7816675
TI  - Experiences of completing cancer therapy: children's perspectives.
AB  - PURPOSE/OBJECTIVES: To explore the child's perspective of experiencing completion
      of cancer treatment. DESIGN: Descriptive, phenomenologic. SETTING: A pediatric
      hematology/oncology clinic in the southwestern United States. SAMPLE: Seven
      children ages 5 to 18 who have completed cancer therapy within the past year and
      who were in remission. METHODS: Open-ended, audiotaped interviews were conducted
      in a quiet setting away from the hospital. Interview data were transcribed and
      analyzed using Colaizzi's eight-step procedure. MAIN RESEARCH VARIABLES: Child's
      description of the experience of completing treatment for cancer. FINDINGS: Six
      theme categories were identified from the data: a gradual realization of normal;
      hierarchical and cyclical recurrence fears; completion embedded in the cancer
      experience; seeking a new normal; modifying relationships; and resolution and
      moving on. The themes were developed into an essential structure that indicated
      that the experience of completing cancer treatment has two faces--one of
      celebration and hope and one of uncertainty and fear. CONCLUSIONS: Children
      completing cancer treatment experience numerous changes. With the assistance of
      healthcare providers, family, and friends, they can begin to move beyond the
      immediate cancer experience. Yet, fears and concerns remain for an extended time
      and must be addressed actively. IMPLICATIONS FOR NURSING PRACTICE: Study findings
      provide an awareness of current practices administered around the time of
      completion and are meant to precipitate dialog with children and families to
      improve follow-up care for childhood survivors.

PMID- 7816674
TI  - The effect of benign breast biopsy on subsequent breast cancer detection
      practices.
AB  - PURPOSE/OBJECTIVES: To determine the effect of benign breast biopsy results on
      the frequency of subsequent breast self-examination (BSE), mammograms, and
      clinical examinations. DESIGN: Retrospective, descriptive design. SETTING: Two
      surgical oncology practices of an academic health science center in the
      southeastern United States and one surgical oncology practice and three family
      practices in another southern U.S. city. SAMPLE: A nonprobability sample
      consisting of 238 women with benign breast biopsies and a comparison group of 243
      women with no histories of breast disease. METHODS: Questionnaires based on
      American Cancer Society (ACS) breast cancer detection guidelines were designed
      and mailed to all women who had benign breast biopsies within the past three
      years at the academic health science center. Similar questionnaires were mailed
      to women randomly selected from three family practices who had no histories of
      breast disease. Chi-square, Kruskal-Wallis one-way analysis of variance, and
      Wilcoxon matched pairs signed-ranks test were used in the data analysis. MAIN
      RESEARCH VARIABLES: Frequency of breast cancer detection practices including BSE,
      mammography, and clinical breast examinations. FINDINGS: In the group that had
      undergone biopsies, breast abnormalities were found by mammogram (38.8%), BSE
      (28.3%), clinical examination (16.9%), and accidental discovery (8.7%). The
      percentage of women performing monthly BSE increased from 47.4% to 67.3%
      postbiopsy (p < 0.0001). The frequency of mammography and clinical breast
      examinations also significantly increased postbiopsy (p < 0.0001). Similarly, the
      postbiopsy rate of BSE, mammography, and clinical breast examinations was higher
      than the rates for the control group. Women whose breast abnormalities were found
      by mammography became significantly more fearful of mammography (p < 0.05).
      CONCLUSIONS: Benign breast biopsies are associated with increased breast cancer
      detection practices. IMPLICATIONS FOR NURSING PRACTICE: All women need to follow
      ACS guidelines for breast cancer detection. Women who have undergone breast
      biopsy may be unduly afraid about the results of future detection practices and
      may need support and encouragement.

PMID- 7816676
TI  - Prostate cancer: controversies surrounding risk, screening, and management.

PMID- 7816677
TI  - Prostate cancer prevention: risk reduction through life-style, diet, and
      chemoprevention.
AB  - PURPOSE/OBJECTIVES: To provide an overview of factors related to life-style,
      diet, and chemoprevention agents that may help lower the incidence of prostate
      cancer in the future. DATA SOURCES: Analysis of literature from MEDLINE (National
      Library of Medicine, Bethesda, MD), published journal articles, papers from
      journal bibliographies, and protocol of the Southwest Oncology Group Prostate
      Cancer Prevention Trial. DATA SYNTHESIS: Information related to prostate cancer
      prevention is accumulating, which may lead to a decreased disease incidence.
      Promising areas include use of chemoprevention, identification of life-style and
      dietary factors that may affect prostate cancer risk, and identification of
      genetic factors involved in prostatic carcinogenesis. CONCLUSIONS: Increased
      understanding of hormonal and genetic changes that occur during prostatic
      carcinogenesis may lead to effective methods of preventing this disease. Prostate
      cancer risk may be reduced by altering life-style and dietary factors and by
      using chemoprevention agents. IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses
      play an important role in prostate cancer prevention through cancer risk
      assessment and patient and public education related to risk-reduction strategies.

PMID- 7816678
TI  - Cancer of the prostate: treatment and nursing implications.
AB  - PURPOSE/OBJECTIVES: To review the clinical manifestations, current treatment, and
      nursing management of prostate cancer. DATA SOURCES: Published articles, book
      chapters, American Cancer Society booklets. DATA SYNTHESIS: Prostate cancer is a
      slow-growing malignancy and usually is asymptomatic in its early stages. It
      causes acute urinary obstruction at more advanced stages, and patients may
      present with metastatic disease. Diagnosis is made by biopsy, and treatment
      options include periodic observation, surgery, radiotherapy hormonal
      manipulation, and chemotherapy with standard or investigational drugs or
      combination therapy. The major complications associated with surgery and
      radiation therapy are transient or permanent incontinence and impotence.
      CONCLUSIONS: Because no definitive method for identifying clinically important
      lesions exists, much controversy surrounds prostate cancer treatment. Issues
      significant to the diagnosis and treatment of all stages of prostate cancer are
      identified, and nursing care concerns focusing on treatment and disease-related
      problems are presented. IMPLICATIONS FOR NURSING PRACTICE: Nursing care focuses
      on providing patients with accurate information to make informed decisions
      regarding treatment for early stage disease, on promoting comfort, and on
      preventing and managing treatment and disease-related complications. Nursing
      diagnoses include knowledge deficit; altered sexual patterns, body image
      disturbance, altered urinary elimination, diarrhea, impaired skin integrity, and
      pain, fatigue, bleeding, and infection, all of which are related to surgery,
      pathologic fractures, spinal cord compression, and edema of the scrotum/lower
      extremities.

PMID- 7816680
TI  - An overview of alternate therapies chosen by patients with cancer.
AB  - PURPOSE/OBJECTIVES: To present an overview of and biomedical perspective on
      alternate cancer therapies used by patients with cancer. DATA SOURCES: Medical,
      nursing, and pharmacy literature. DATA SYNTHESIS: Two recent studies reported on
      patients choosing alternate care products with limited and anecdotal information
      obtained from the lay literature and their social group. Yet, the biomedical
      community has access to numerous excellent studies, documentation resources, and
      commentaries related to alternate therapies. CONCLUSION: Provision of known
      biomedical information related to alternate therapies would provide patients with
      an opportunity to make informed healthcare choices. IMPLICATIONS FOR NURSING
      PRACTICE: Nurses, using information from biomedical sources, can serve as
      informational resources for patients with cancer making healthcare decisions.

PMID- 7816679
TI  - A descriptive study of immune status in patients undergoing colorectal surgery:
      lymphocyte phenotypes.
AB  - PURPOSE/OBJECTIVES: To describe immune status in patients prior to colorectal
      surgery for cancer, to establish values to serve as a baseline for subsequent
      analyses, and to describe a procedure for studying phenotypes of the immune
      system, elucidating its advantages. DESIGN: One component of a larger
      longitudinal survey. SETTING: Two large, inner-city university hospitals and two
      of their affiliated hospitals in the northeastern United States. SAMPLE: Patients
      undergoing surgery for colorectal cancer (N = 94). Subjects were primarily male
      (n = 57) and Caucasian (n = 85) and ranged in age from 26-88 years (mean = 63).
      Seventy-seven percent (n = 73) had cancer, 23% (n = 21) had benign diseases or
      conditions. METHODS: Flow cytometry analysis of lymphocyte phenotypes was
      performed on blood samples drawn from patients before they underwent surgery for
      colorectal cancer. MAIN OUTCOME MEASURES: The average absolute lymphocyte subset
      levels and the average relative lymphocyte subset levels of blood samples taken
      from patients undergoing surgery for colorectal cancer were compared (using t
      tests) with the subset levels of two normal reference samples. FINDINGS: The
      average absolute lymphocyte subset levels and average relative lymphocyte subset
      levels of patients undergoing surgery for colorectal cancer fell within normal
      ranges. CONCLUSIONS: These findings suggest that this sample of patients
      undergoing surgery has one essential element of an intact immune system--normal
      levels of lymphocyte subsets. IMPLICATIONS FOR NURSING PRACTICE: There is no
      indication preoperatively that this population is at a higher risk for infection
      or delayed wound healing. However, there may be other times in the illness
      trajectory when the immune system does become compromised, and these values prior
      to surgery will serve as a baseline to identify changes in patients' immune
      status over time. Further longitudinal studies are necessary.

PMID- 7816681
TI  - Establishing an integrated framework for documentation: use of a self-reporting
      health history and outpatient oncology record.
AB  - PURPOSE/OBJECTIVES: To describe the development and implementation of a succinct
      documentation system that provides all oncology team members with a quick and
      systematic approach to gathering information for care planning. DATA SOURCES:
      Published articles and books. DATA SYNTHESIS: The Nursing Documentation Committee
      at the Ottawa Regional Cancer Centre designed and implemented a self-reporting
      health history (SRHH) that provides baseline data for care planning and an
      outpatient oncology recore (OOR) that provides ongoing documentation of all
      patient assessment findings and subsequent care. The OOR combines flowsheet and
      progress note documentation on one form. These tools are used by all members of
      the oncology team. CONCLUSIONS: Through consistent use of the SRHH and OOR,
      quality of documentation has increased and nursing time spent on charting has
      decreased, thus enabling the oncology team to focus on direct patient care
      activities. Furthermore, enhanced communication among members of the oncology
      team has resulted in improved continuity of patient care. IMPLICATIONS FOR
      NURSING PRACTICE: The SRHH and OOR are time-efficient and cost-effective tools
      that can assist nurses in meeting legal, professional, and accreditation
      documentation standards.

PMID- 7816682
TI  - A patient's guide to Taxol.
AB  - PURPOSE/OBJECTIVES: To present a teaching booklet designed to educate patients
      and their families about Taxol (Bristol-Myers Squibb Co., Princeton, NJ). DATA
      SOURCES: Published articles, manufacturer's guidelines, and National Cancer
      Institute protocol. DATA SYNTHESIS: The booklet presents information about Taxol
      and its contraindications, drug administration, side effects, and symptom
      management. CONCLUSIONS: Initial evaluation indicates that the booklet has been
      an effective home reference guide for patients and their families. IMPLICATIONS
      FOR NURSING PRACTICE: The booklet reinforces basic patient education regarding
      Taxol and assists patients and families in early detection of side effects and
      complications.

PMID- 7816683
TI  - Cultural-specific questions are key to care planning for ethnic minorities.

PMID- 7816684
TI  - Teaching Spanish-speaking patients and their families about pain management.

PMID- 7816685
TI  - Caring for patients with cancer on St. Croix.

PMID- 7816686
TI  - Establishing an outreach network for rural African Americans.

PMID- 7816687
TI  - [Inferences drawn from communication in a neonatal pathology ward].
AB  - The general process of communication is reviewed in order to ascertain how
      neonatologists should approach not-verbal, not intentional messages coming from
      premature newborns, which ask suitable answers from a therapeutic and educational
      point of view. The author recalls the Als Synactive Theory that enables to
      understand the signals coming from the newborn allowing all the care-gives to
      reply coherently to expressed physical and physiological needs.

PMID- 7816688
TI  - [Communication within a neonatal intensive therapy unit].
AB  - The existing literature stresses the discomfort fatigue, and tension in the
      context of Neonatal Intensive Care Unit nursing work, which often lead to the so
      called "burnt-out syndrome". It is not surprising that this might be prevalent in
      a department that it deals with children who are at the beginning of their lives
      but under constant threat of death. In order to overcome the above-mentioned
      difficulty starting from 1982 the Author arranged weekly meeting with the staff
      of Neonatal Intensive Care Unit of the Treviglio-Caravaggio Hospital (Bergamo).
      In this article, it is underlined that, in order for the work to develop, the
      staff needed to go through various mental states, which could be viewed as
      "typical phases", the most important resulting the "emotional atmosphere". Only
      after working through these phases the work group will discover his ability to
      observe the child as an integrated being with biological and emotional components
      and so will be able to perform his caring function.

PMID- 7816689
TI  - [Interdisciplinary communication in neonatology].
AB  - An efficient and rational neonatal intensive care should be regionalized.
      Interdepartmental communication among obstetricians, neonatologists,
      pediatricians, neurologists should be planned and stirred between the reference
      centre and the outside hospitals, as well as in the catchment area. In this way
      only, such important goals as in-utero and neonatal transfer, training of
      obstetric neonatal teams, regionalized epidemiology and care evaluation can be
      achieved. In the same way, communication inside the hospital among doctors,
      nurses and parents is basic to humanize medical care.

PMID- 7816690
TI  - [Communication in the neonatal intensive therapy unit: the opinions of parents
      and of medical personnel compared].
AB  - Within the framework of an European international project, the issue of parents
      staff communication in Neonatal Intensive Care Units was explored. 5 Italian unit
      participated in the project. 80 mothers and 62 fathers of singleton, not
      malformed, very low birthweight babies were interviewed during the fourth week of
      their baby's life, while the views of the health personnel (60 doctors and 106
      nurses) were collected through an anonymous, self-administered questionnaire.
      Most of the staff feels that parents should be informed completely about their
      baby's conditions and prognosis, while the actual practices about transmission of
      information are reported differently according to professional status: more
      nurses than doctors feel that the information is not as complete as it should be.
      Uncertainty of prognosis is the most commonly quoted reason for restricting the
      information. Parents, on the other hand, are generally satisfied about the
      information received, although some of them complain about the style of
      communication, and especially the need to ask repeatedly in order to be informed.
      These results show some of the gaps existing in communication both within the
      staff and with parents, and suggest possible ways of improvement.

PMID- 7816691
TI  - [The birth of a neonate with a congenital malformation].
AB  - The birth of a neonate with congenital malformation for the parents determines
      often a process of adaptation with a phase of shock, a phase of incredibility and
      scare and, at last, one of adaptation and equilibration. The reactions of the
      parents and the difficulties they meet in the relation with the child depend
      mostly on the characteristics of the malformation and on the explanations and
      support they receive. The Health care personnel knows well that the communication
      of a diagnosis of a congenital malformation to the parents is frustrating. Both
      the Pediatrics and the Gynaecologist have to considerate seriously and
      consciously this relational question, considering that the communication is a
      interpersonal relationship and therefore flexible and changeable in every case.
      After this previous statement we consider it useful to report advises taken from
      the literature: the parents have to be informed at once the diagnosis is
      confirmed, possibly at the same time and in presence of the infant; the
      communication should be done both from the Pediatrics and the Gynaecologist,
      possibly at the same time; the communication should take place in a private
      atmosphere and with plenty of time.

PMID- 7816692
TI  - [Permanent neurological damage].
AB  - Permanent neonatal neurologic injury is often a result of intraventricular and
      intraparenchymal hemorrhage, hydrocephalus or porencephaly, cerebral congenital
      malformation, congenital infections, or hypoxic-ischemic encephalopathy syndrome.
      The damage must be communicated to the newborn's parents, who will obviously ask
      about their child's future. The news given to both parents must be truthful,
      showing a sense of empathy, with some degree of the problem's severity withnel
      however, so as to allow the time necessary for them to adjust to the blow slowly.
      It is also useful to emphasize that the individual medical facility is capable of
      timely diagnoses, correct therapy, and long-term follow-up. In short, of truth
      and human kindness.

PMID- 7816693
TI  - [Neonatology. Medicolegal considerations].
AB  - The authors underline the relevance of the medical-legal participation and
      contribution in dealing with the problems of neonatology, and delineate their
      area of communication in this matter. They first remind the principles (legal,
      but also ethical) that need to be referred to: the concept of health, the
      attention of a real interest for the children, and the engagement to protect the
      life of the newborn, even though premature. Secondly, they discuss some specific
      questions, as 1) adequate information and communication; 2) informed consent; 3)
      care and withdraw treatment; 4) communication between different operators, and
      finally; 5) Ethical Committees as appropriate consultation reference, especially
      for more complex cases.

PMID- 7816694
TI  - [Communication between neonatologists and obstetricians].
AB  - A close communication between obstetricians and neonatologists represents a basic
      tool for the improvement of newborn care. We shall illustrate what
      obstetric/neonatological communication tools are applied in our hospital. We
      believe the cooperation between obstetricians and pediatricians/neonatologists is
      of great importance for the health of both mother and newborn, thus it should
      become common practice even in those hospitals where neonatological intensive
      therapy units do not exist.

PMID- 7816695
TI  - [Support for the parents after the death of a newborn infant].
AB  - The neonatologist in NICU has many duties, first of all caring the baby and
      supporting the parents in facing stressing situations. When the baby dies most
      doctors think their job is over, and only in few hospitals there is the
      opportunity for the parents to meet the staff again. We report our recent
      experience to meet parents after baby's death. We offer them this possibility
      when they are leaving the hospital and, after about one month, we call them by
      phone to arrange an appointment. We have realized that they need to talk at least
      once with the staff (doctors and nurses) to examine and solve doubts about cares
      and to relieve their sufferance. In our experience, even limited, we found that
      nobody refuses this opportunity and that in most instances parents required more
      than one meeting and, finally, that talking of the baby with people who took care
      of him helps them in accepting baby's death. We found this experience very useful
      both for parents and staff, so we hope this opportunity will extend to other
      hospitals.

PMID- 7816696
TI  - [An update on the treatment of otitis media with effusion in children. The
      indications for transtympanic drainage].
AB  - Otitis media with effusion (O.M.E.) is a frequent child's condition, with
      generally spontaneous recovery. Only a few cases, with some complications and
      chronic-O.M.E., present hearing loss and later verbal and academic delayed
      performances. We report our experience on treatment by tympanostomy tubes for
      O.M.E., at the Clinic of otolaryngology of the University of Pisa, since 1981 to
      1993, resulting a progressively reduced number of these operations in the last
      period. We believe that both the inflamed upper airways care, and first choice
      adenoidectomy can explain the trend. Ventilation tubes must be placed only for
      persistent picture of O.M.E. and possibility of invalidity.

PMID- 7816697
TI  - [Allergy to cow's milk proteins: the sensitivity of specific and nonspecific
      laboratory tests].
AB  - Authors report their experience of a population of 308 children affected by cow's
      milk allergy who presented gastrointestinal, respiratory and cutaneous symptoms.
      Diagnosis was based on challenge with cow's milk proteins and on laboratory
      specific tests (RAST, prick test) and non specific ones (PRIST, eosinophil count,
      1-h xylose test, occult blood in the stools), following ESPGAN criteria. The
      patients were subdivided in 3 groups: a) patients with prevalent gastrointestinal
      symptoms; b) patients with prevalent cutaneous symptoms and c) patients with
      both, gastrointestinal and cutaneous symptoms. The sensitivity of the employed
      tests was evaluated either in the whole patient population or in the there group
      according to symptoms. Our data show a high sensitivity of the RAST for cow's
      milk (70%) versus a lower sensitivity of prick test (53%) when the whole patients
      population was considered. Moreover statistically important differences of the
      sensitivity of the various tests were found when the three groups of patients
      were considered, as well as when such a comparison was done in patients
      subdivided according to age (more or less than 6 months). Finally the concord
      between RAST and prick test was evaluated in the three groups.

PMID- 7816698
TI  - [The early diagnosis of congenital hip dysplasia: a proposal for a differentiated
      echographic screening].
AB  - Prevention of congenital hip dislocation is one of the main goals of pediatric
      activity. 839 newborn outpatients, with six months follow-up at least, were
      recruited at the Pediatric Clinic of the Catholic University of Rome, from
      January 1991 to December 1992. Every newborn baby was clinically examined for
      congenital hip dysplasia (CHD) at nursery and afterwards in the ambulatory. Hip
      sonography was performed, according to Graf's technique, in 504 babies (60%): 17
      resulted pathological (3.3%), 30 borderline (6%) and 457 normal (90.7%).
      Ultrasonographic and clinical findings were compared. Clinical examinations at
      nursery and ambulatory have shown low sensitivity (21.3% and 34% respectively) in
      detecting dysplastic hips. Present experience confirms ultrasonography value in
      the diagnosis of CHD and the utility of its use in a general screening programme.

PMID- 7816699
TI  - [Changes in liver protein synthesis in the preterm newborn infant of a pre
      eclamptic mother and/or with intrauterine growth retardation].
AB  - To verify in the preterm newborn the hypothesis, recently proposed by some
      authors, of an hepatosynthetic deficiency, blood fibrinogen (FIB), prothrombin
      time (PT) and albumin (ALB) levels at birth were studied in 44 neonates, selected
      to obtain 4 groups of the same number and gestational age, different only for the
      presence of intrauterine growth retard and preeclampsia during pregnancy. In the
      newborns born of preeclamptic pregnancies, FIB, PT and ALB blood levels at birth
      resulted lower, but not significantly, than in those born of normal pregnancies;
      in SGA newborns the values (except for albumin) resulted significantly lower than
      in AGA newborns (FIB = 168 +/- 63 mg/dl vs 223 +/- 55 mg/dl; p < 0.01; PT = 51 +/
      15% vs 71 +/- 19%; p < 0.001). Besides, PT values resulted significantly lower
      (p < 0.01), in presence of normal pregnancy, in SGA than in AGA newborns, while
      FIB values resulted significantly lower (p < 0.01), in presence of preeclampsia,
      in SGA than in AGA newborns. It seems that, in preterm newborn, the intrauterine
      growth retard, rather than preeclampsia, would condition lower blood levels of
      the examined seric proteins. These results could be explained by hypothesizing,
      in the SGA preterm newborn, 3 possible etiopathogenetic mechanisms: 1) increased
      turnover of hepatosynthetized seric proteins, such as albumin; 2) deficiency of
      liver enzymes involved in proteic synthesis, already demonstrated for some
      coagulation factors; 3) diminished amino acidic substratum, necessary for proteic
      hepatosynthesis, caused by poor amino acidic passage through placenta, possible
      in presence of intrauterine growth retard. This would probably be the most
      important mechanism in causing low levels of the examined seric proteins.

PMID- 7816700
TI  - [The validity of screening for hypertension in school-age children. A cross
      sectional study of a sample of 861 pupils of the towns of Local Health Unit No.
      22 of Vittoria (Sicily)].
AB  - In order to define the validity of a screening program for hypertension in
      schools, aiming to prevent an hypertensive status in adult age, we screened 861
      children from schools on the area of our Medical District (U.S.L. 22--Vittoria-
      Sicily). The object of our study is to search for risk factors of hypertension,
      detectable at school age and, if existing, which age is more suitable for a
      screening program. We randomly sampled 861 children from different schools, aging
      6, 10 and 13 years. The first step was to define the prevalence of hypertension
      and obesity in the sample, and the correlation between the two factors
      (transversal study). We found an overall prevalence of obesity at 6, 10, and 13
      years of 6.69%, 18.22% and 17.7% respectively. The prevalence of hypertension was
      4.01%, 11.4%, and 6.98% at 6, 10 and 13 years respectively. The second step is to
      create a personal record of each child, which will be followed up to the age of
      18 years, containing familial and nutritional informations, periodic evaluations
      of height, weight, blood pressure and biologic sampling (longitudinal study). Our
      preliminary results confirmed the correlation between obesity and hypertension,
      although they do not help to clarify why the prevalence of hypertension decreases
      from 10 to 13 years whereas obesity maintains the same prevalence at the
      mentioned ages.

PMID- 7816701
TI  - [A new growth curve].
AB  - A growth curve is presented, that using the Tanner and Whitehouse's 50th centile,
      plots the height versus weight, both for males and females. The age is gives as
      parameter on the curves. In this way, weight, height and age are merged on a
      single chart for every sex. After exemplifying its advantages, the simpler relief
      of deviation from the values of the height-weight medians on the various ages,
      because the values of weight refer to the real height (and back), not to the age.
      With the same rule, curves relating to 10th and 90th centiles are processed by
      Tanner and Whitehouse's values. Collating between them, curves allow some
      morphological relief. Moreover, for both referred to the 50th centile of Tanner
      and Whitehouse curves (for the male sex and the female one), is presented a
      simple mathematical expression of interpolation, which shows and excellent
      representation of the measured dates. This expression is composed of a third
      degree polynomial (cubic), which is fitted to the dates by the method of least
      square. The result of the correlation height-weight allows both to synthesize the
      dates in a sole expression and a simpler relief of discordance in the growth.

PMID- 7816702
TI  - [Diphtheria--tetanus--pertussis].
AB  - Authors examine prophylaxis in fighting diphtheria, tetanus, pertussis over last
      fifty years and the results recently obtained in this field. They foresee
      improving sanitary conditions in the future of our country.

PMID- 7816704
TI  - [Partial deletion of the short arm of chromosome 4 (the Wolf-Hirschhorn syndrome)
      with reference to the neurological and electroencephalographic aspects].
AB  - We describe a case of Wolf-Hirschhorn syndrome (partial deletion of the short arm
      of chromosome 4). The syndrome is characterized by mental and growth retardation
      and characteristic facial dysmorphism. The fetus was karyotyped for severe
      intrauterine growth retardation diagnosed on routine ultrasound. High resolution
      chromosomal analysis of infant and parents showed "de novo" deletion. Very
      interesting in our case are ictal phenomena and neurological development.

PMID- 7816705
TI  - [Polythelia as a sign of other congenital malformations: a clinical example].
AB  - The authors describe the clinical history of a girl with severe chronic
      constipation due to anterior ectopic anus, associated with supernumerary nipples.
      The authors underline the importance of possible associations between
      supernumerary nipples and other congenital anomalies.

PMID- 7816706
TI  - [Discordance in the onset of celiac disease in monozygotic twins].
AB  - Coeliac disease (CD) is a gluten intolerance caused by a combination of genetic
      and environmental factors such as nutrition and infections. Monozygotic twins
      appear to have a concordance for CD up to 71%. This paper reports a third case of
      late onset of CD in monozygotic twin girls. The twins were defined as monozygotic
      based upon paired clinical and laboratory examinations. Clinical examinations
      included genotypic, phenotypic and dermatoglyphic analysis, while laboratory
      examinations included HLA typing and blood groups. Following European Society of
      Pediatric Gastroenterology and Nutrition criteria, CD was diagnosed in both
      girls, though 4 years and 8/12 months apart. The twins achieved clinical,
      laboratory and histological remissions within 1 year, after the institution of a
      gluten-free diet. Genetic markers are undoubtedly the main precondition for CD
      development. Environmental factors, however, may play a more significant role in
      triggering the onset of disease.

PMID- 7816707
TI  - [The multiple exostoses syndrome. 3 cases in one family].
AB  - Multiple exostoses syndrome is a rare autosomal dominant disorder that affects
      the enchondral skeleton during growth. The formation of numerous exostoses causes
      deformities of bones and joints. Degenerative malignant changes are described. A
      careful follow up during paediatric age is required. Three new cases in the same
      family are reported in this paper.

PMID- 7816708
TI  - Cytomegalovirus retinitis in persons with AIDS. Selecting therapy for a sight
      threatening disease.
AB  - Almost one third of persons with AIDS acquire retinitis caused by the
      opportunistic cytomegalovirus (CMV). Both ganciclovir and foscarnet have been
      approved for treatment of CMV retinitis and are equally effective. However, their
      side effects are not the same, and each may have a different impact on the
      overall course of HIV infection and AIDS. The drug chosen should be administered
      promptly when sight-threatening disease is diagnosed to ensure maximal vision for
      the longest time.

PMID- 7816703
TI  - [An echocardiographic study of the left ventricular functional indices in
      pediatric patients on hemodialysis and in treatment with recombinant human
      erythropoietin (r-HuEPO)].
AB  - Recombinant human erythropoietin (r-HuEPO) is efficient in the treatment of
      anaemia in chronic renal failure on hemodialysis. We investigated the changes in
      cardiac function under r-HuEPO therapy using echocardiography. Seven patients
      with severe renal anaemia (Ht 19%) were treated with 50 U/kg r-HuEPO EV three
      times/week. Echocardiographic studies were performed in the anemic state and when
      hematocrit values were stable at levels (Ht 30%). Left ventricular function as
      showed by fractional shortening (D%) improved, the thickness of the
      interventricular septum and left ventricular hypertrophy were reduced. Our data
      indicate that the correction of renal anaemia by r-HuEPO can improve myocardial
      function in patients on maintenance hemodialysis.

PMID- 7816709
TI  - Institutional placement for patients with Alzheimer's disease. How to help
      families with a difficult decision.
AB  - Family members confronting the difficult decision of whether to place a patient
      with Alzheimer's disease in an institution find it helpful to have explicit
      criteria on which to base their decision. Regular incontinence of bladder and
      bowel, inability of the patient to cooperate in his or her care, inability of the
      patient to realize that he or she is at home with familiar caregivers, the
      withdrawal of a paid caregiver, risk to the health of the primary caregiver, and
      primary caregiver burnout are all grounds for considering institutional
      placement. Options include assisted living facilities, dementia-specific assisted
      living facilities, general nursing homes, and nursing homes with dementia
      specific care units. Institution-like care can be provided at home, but this is
      expensive and may be inconvenient and stressful for family members. Hospice care
      is appropriate at the end of the patients's life.

PMID- 7816710
TI  - Otitis media with effusion in infants and children. Primary care concerns
      addressed from an otolaryngologist's perspective.
AB  - In 90% of children, otitis media with effusion resolves within 3 months. When it
      persists longer, it is considered chronic. Initial treatment of chronic otitis
      media with effusion is repeated courses of antibiotics, and a short course of
      steroids may be appropriate. Use of antihistamines and decongestants has not been
      shown to be efficacious, although they may be beneficial when inhalant allergies
      contribute to eustachian tube dysfunction. Persistent effusion leads to
      conductive hearing loss, which may have a significant impact on language, speech,
      and intellectual development. Thus, surgical therapy consisting of insertion of
      tympanostomy tubes and, in selected cases, adenoidectomy is indicated to improve
      hearing and prevent long-term sequelae.

PMID- 7816711
TI  - Don't swallow government-controlled healthcare--even one bite at a time!

PMID- 7816712
TI  - Hypercalcemia. How to pinpoint the cause and customize treatment.
AB  - Hypercalcemia is a commonly diagnosed metabolic disorder that is most often
      caused by primary hyperparathyroidism or malignant disease. Parathyroid hormone
      assays are useful and reliable in differential diagnosis. Treatment depends on
      the degree of hypercalcemia, symptoms, and the underlying cause. Pharmacologic
      therapy, especially with bisphosphonates, may effectively lower serum calcium
      levels, but the underlying cause of the hypercalcemia must be treated to
      definitively restored normocalcemia.

PMID- 7816713
TI  - Polymyalgia rheumatica or Lyme disease? How to avoid misdiagnosis in older
      patients.
AB  - This case report demonstrates the need to consider Lyme disease in older patients
      who present with nonspecific signs and symptoms often seen in polymyalgia
      rheumatica, particularly a markedly elevated erythrocyte sedimentation rate
      (ESR). ESRs greater than 100 mm/hr are common in polymyalgia rheumatica, but
      rates higher than 85 mm/hr are also possible in Borrelia infection. Because
      positive serologic findings for Lyme disease have been noted in patients with
      polymyalgia rheumatica who have been exposed to endemic areas, differential
      diagnosis must be based on clinical manifestations. Response to therapy should be
      monitored closely to confirm the diagnosis and avoid the adverse consequences of
      inappropriate treatment. The potentially deleterious effect that corticosteroids
      can have on Lyme disease must be considered in the decision to treat polymyalgia
      rheumatica.

PMID- 7816714
TI  - Checks the bounce: New Year's resolutions for physicians.

PMID- 7816715
TI  - Venous thrombosis. Lifting the clouds of misunderstanding.
AB  - Deep venous thrombosis (DVT) is often occult and difficult to recognize
      clinically. The diagnostic approach should begin with color-flow (duplex)
      ultrasound, noninvasive functional tests such as plethysmography, or both.
      Because these tests are not 100% sensitive, contrast venography or magnetic
      resonance imaging may be necessary in a patient with unexplained symptoms. A
      baseline ventilation-perfusion scan should be considered for any patient with
      DVT, because there is a high incidence of clinically inapparent pulmonary
      embolism. In the absence of contraindications, systemic or regional thrombolytic
      therapy should be considered for every patient with acute DVT. Surgical
      thrombectomy may be indicated for patients with a large, obstructive proximal
      thrombus. At a minimum, routine treatment should start with heparin and proceed
      to oral warfarin (Coumadin, Panwarfin, Sofarin), which should be continued for 3
      months. Recurrent DVT after cessation of therapy warrants lifetime use of
      anticoagulants. A filter should be placed in the inferior vena cava whenever a
      large, poorly adherent thrombus is identified or when there is progression of
      thrombosis despite an anticoagulant regimen.

PMID- 7816716
TI  - Suspected pulmonary embolism. The difficulties of diagnostic evaluation.
AB  - It is impossible to prove or disprove a diagnosis of acute pulmonary embolism on
      clinical grounds. Diagnostic evaluation is best carried out by first attempting
      to identify a provable alternative diagnosis that can explain a patient's
      symptoms. Once the diagnosis of pulmonary embolism is seriously considered, a
      ventilation-perfusion (V/Q) scan is the next step. A positive ("high
      probability") or negative ("normal-perfusion") scan is an appropriate diagnostic
      end point. Unfortunately, most V/Q scans are nondiagnostic, and the workup must
      be pursued further. Color-flow (duplex) ultrasound, if available, is the next
      logical step. If a site of deep venous thrombosis cannot be identified, pulmonary
      angiography is indicated. Newer methods, such as D-dimer measurement and spiral
      computed tomography, are being studied.

PMID- 7816717
TI  - Acute pulmonary embolism. Aggressive therapy with anticoagulants and
      thrombolytics.
AB  - Patients with acute pulmonary embolism are at risk for early death or chronic
      morbidity. Appropriate therapy can dramatically reduce the incidence of both.
      Oxygen and heparin therapy should be started as soon as the diagnosis is
      suspected. The condition of a hypotensive patient with right ventricular overload
      from acute pulmonary embolism usually is made worse by a fluid challenge;
      hypotension may be relieved by preload reduction or even by gentle diuresis.
      Norepinephrine (Levophed), isoproterenol hydrochloride (Isuprel), and epinephrine
      are the pressor agents of choice. Immediate thrombolysis is the standard of care
      for any patient with significant hypoxemia or hypotension due to proven pulmonary
      embolism. Beyond this, the potential benefit of using thrombolytic agents should
      be considered routinely for every patient with proven pulmonary embolism.
      Surgical embolectomy is useful for unstable pulmonary embolism when there are
      absolute contraindications to thrombolysis or when thrombolytic therapy fails.
      Empirical use of thrombolysis may be considered as a last-ditch effort for a
      critically ill patient when there is a high clinical suspicion of pulmonary
      embolism. Standard closed-chest cardiopulmonary resuscitation is ineffective when
      the pulmonary circulation is obstructed by thrombus. Emergency thoracotomy or
      femorofemoral cardiopulmonary bypass is appropriately used in patients with full
      cardiac arrest from pulmonary embolism.

PMID- 7816718
TI  - Chronic pulmonary embolism. Often misdiagnosed, difficult to treat.
AB  - Chronic thromboembolic pulmonary hypertension with cor pulmonale is an extremely
      debilitating disease that (1) is more common than generally recognized, (2) is
      often misdiagnosed, and (3) is difficult to treat. When a patient has persistent
      exertional dyspnea with no obvious cause, a ventilation-perfusion scan,
      echocardiography, and (if indicated) pulmonary angiography should be done.
      Prevention is especially important because by the time a patient is symptomatic,
      the disease is already far advanced and hemodynamic reserves are greatly reduced.
      Prevention of recurrence mandates lifetime anticoagulation and placement of a
      vena cava filter. The only effective treatment is pulmonary endarterectomy, which
      is being performed at an increasing number of specialty centers across the United
      States.

PMID- 7816719
TI  - Carpal tunnel syndrome. A guide to prompt intervention.
AB  - Carpal tunnel syndrome is the most common entrapment neuropathy in the United
      States. The diagnosis should be considered for any patient with hand or wrist
      pain, weakness, or numbness. Changes in sensory conduction velocities across the
      wrist appear to be the most sensitive electrophysiologic indicators of the
      condition. Treatment of mild cases involves avoiding the precipitating activity,
      wrist splinting, and local steroid injections; surgical decompression is often
      required for moderate and severe cases. Overall, prognosis relates directly to
      the severity of the median nerve injury at diagnosis, the clinical cause, and the
      mode of treatment.

PMID- 7816720
TI  - Hirsutism and virilization. A systematic approach to benign and potentially
      serious causes.
AB  - A woman with excessive body hair may visit a physician with concerns about
      fertility and general health as well as appearance. Fortunately, the cause is
      usually benign, most often polycystic ovarian syndrome. However, life-threatening
      causes must be quickly ruled out. Hirsutism secondary to endocrinopathies and
      tumors can typically be recognized by the rapid progression of hair growth;
      patients should be referred for prompt evaluation and treatment. Benign causes
      can usually be treated effectively with medical and mechanical methods.

PMID- 7816721
TI  - Genetic variation of residual feed consumption in a selected Finnish egg-layer
      population.
AB  - The purpose of the study was to estimate the heritability of residual feed
      consumption (RFC) and the genetic correlations between RFC and economically
      important traits. The genetic progress after four generations of selection for
      RFC and the changes in economically important traits were also investigated. A
      selection experiment for RFC was carried out from 1983 to 1987. The total data
      consisted of 3,750 birds and 2,661 records. The (co)variance components were
      calculated using derivative-free bivariate animal model restricted maximum
      likelihood (REML). Breeding values were estimated for calculating genetic
      progress in RFC and correlated responses in the other traits. The heritability of
      RFC calculated from the whole recorded period (16 to 42 wk) and using all 2,661
      records was .46 (+/- .04). The genetic correlations between RFC and egg mass,
      number of eggs, egg weight, and body weight were not significant. The genetic
      correlation between RFC and feed consumption was .50 (+/- .04). The breeding
      value estimates indicated a moderate genetic progress in RFC due to selection.
      Feed consumption was decreased and body weight gain showed reduction in the last
      two generations. No change could be found in egg mass, number of eggs, egg
      weight, age at first egg, or body weight.

PMID- 7816722
TI  - A question on the locations of the tardy feathering and henny feathering loci in
      the chicken.
AB  - The locus for tardy feathering (t), previously mapped to the long (q) arm of
      chromosome 1 of the chicken, was tested for genetic linkage with both the NM 7659
      t(Z;1) rearrangement break point (RB) and the henny feathering (Hf) locus. The RB
      is proximal to the centromere on 1q, and Hf has been reported to be on the
      proximal one-third of the same arm. Independent segregation of all three markers
      was found in two separate backcrosses.

PMID- 7816723
TI  - Selection for eight-week body weight in two randombred chicken populations under
      altered water to feed ratios. 2. Feed intake, water intake, and abdominal fat
      levels.
AB  - Four experiments were conducted to investigate feed and water intake, feed
      efficiency, and abdominal fat levels of six lines of chickens developed from two
      randombred control populations following selection for high 8-wk BW under high
      (1.6%), low (.2%), and normal (.4%) dietary salt selection environments. The
      Athens-Canadian Randombreds (AC) and Athens Randombreds (ARB) served as base
      populations for development of the six lines. Progeny from these lines were
      evaluated in the first, fifth, sixth, and seventh generations in Experiments 1,
      2, 3, and 4, respectively. In Experiment 1, abdominal fat levels were shown to be
      inversely related to dietary salt level. The lowest abdominal fat level was
      observed in birds fed the 1.6% salt diet and the highest abdominal fat level in
      birds fed the .2% salt diet. Birds receiving the normal (.4%) salt diet had
      intermediate abdominal fat levels. In Experiments 2, 3, and 4, selected lines
      were exposed to different dietary salt levels to measure both line and dietary
      salt response patterns. Significant (P < .05) differences were observed between
      genotypes (AC vs ARB) and between dietary salt treatments for BW, feed and water
      intake, and water to feed ratio. However, there was no evidence of genetic change
      between lines in abdominal fat level as a result of selection under different
      salt environments.

PMID- 7816724
TI  - Evaluation of molt induction to body weight loss of fifteen, twenty, or twenty
      five percent by feed removal, daily limited, or alternate-day feeding of a molt
      feed.
AB  - Postmolt egg production variables were compared among hens induced into molt by
      feed removal, by limited daily feeding of a low-density and low-energy molt feed
      at 22.8 g per hen, or by limited alternate-day feeding at 45.5 g per hen, until
      approximate body weight loss of 15, 20, and 25% was obtained. Hens were housed
      two per cage (25.4 x 45.7 cm) in a house of environmental design, and photoperiod
      was reduced to 8 h during the 28-d molt period. When target body weight loss was
      obtained, packed cell volume was determined and hens were maintained on 45.5 g/d
      of 1.2% calcium prelay feed through the 28-d molt period. Egg production and
      mortality were recorded daily; egg weight, egg specific gravity, body weight, and
      feed intake were recorded at 4-wk intervals postmolt. Packed cell volume of hens
      molted by feed removal (36.4%) was higher (P < .01) than that of alternate-day
      (34.1%) or daily limited (33.6%) hens. Hens that lost 25% of their body weight
      had higher packed cell volume (36.3%) than hens that had body weight loss of 20%
      (34.4%) or hens that lost 15% (33.4%). Postmolt mortality and egg production were
      not different (P > .05) as a result of molt induction method or percentage body
      weight loss. At the 4th wk postmolt, body weights were 50 and 57 g heavier for
      hens that had lost 15% body weight than those that lost 25 or 20%, respectively,
      and egg production was negatively linearly related to body weight loss.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7816725
TI  - The effect of microaerosolized hydrogen peroxide on bacterial and viral poultry
      pathogens.
AB  - The effect of microaerosolized H2O2 on bacterial and viral poultry pathogens was
      investigated. Bacterial cultures and viruses were dried on sterile glass Petri
      dishes and subjected to direct and indirect 5% (H2O2) microaerosol mist. In the
      trials using Escherichia coli and Staphylococcus aureus, there was complete
      inactivation following exposure to H2O2. Using Salmonella typhimurium, indirect
      exposure resulted in only partial inactivation whereas direct exposure to H2O2
      gave complete inactivation. For the viruses studied, 5% H2O2 microaerosol mist
      completely inactivated infectious laryngotracheitis virus. Newcastle disease
      virus, infectious bronchitis virus, and avian influenza virus showed reduced
      infectivity but were not completely inactivated. Avian reovirus susceptibility
      varied with the method of exposure and infectious bursal disease virus was highly
      resistant. The use of 10% H2O2 mist, however, resulted in total inactivation of
      infectious bursal disease virus. The effect of 10% H2O2 on equipment and selected
      materials representative of a hatcher or poultry house was investigated. A solar
      cell calculator, a thermostat containing a microswitch, and samples of uncoated
      steel, galvanized steel, and uncoated aluminum were subjected to 10 fumigation
      cycles. No damage was detected in the calculator and the thermostat. Both the
      uncoated steel and the galvanized steel showed signs of oxidation. The aluminum
      did not show signs of oxidation.

PMID- 7816726
TI  - Individual and combined effects of feeding Fusarium moniliforme culture material,
      containing known levels of fumonisin B1, and aflatoxin B1 in the young turkey
      poult.
AB  - The individual and combined effects of fumonisin B1 (FB1) and aflatoxin B1 (AF)
      were evaluated using a 2 x 2 factorial with treatments of 0 and 75 mg FB1/kg feed
      and 0 and 200 micrograms AF/kg feed. Each of the four diets was fed to eight pen
      replicates of six poults from Day 1 to 21. Body weight gain was reduced (P < .05)
      by AF and the FB1-AF combination. Poults fed AF or the FB1-AF combination were
      less efficient (P < .05) in converting feed to gain. Fumonisin B1 increased (P <
      .05) liver weights whereas AF and the FB1-AF combination increased (P < .05)
      spleen weights. The AF and the FB1-AF combination decreased (P < .05) serum
      concentrations of albumin, total protein, and cholesterol. Fumonisin B1 and the
      FB1-AF combination increased (P < .05) serum sphinganine:sphingosine (SA:SO)
      ratios. Treatment-associated lesions were observed only in the liver.
      Hepatocellular hyperplasia and biliary hyperplasia were seen in poults fed 75 mg
      FB1/kg and 200 micrograms AF/kg, respectively. The combination of FB1 and AF
      caused an increased primary immune response to sheep red blood cells. However,
      the phytohemagglutinin delayed hypersensitivity response was not affected by
      dietary treatment. These data indicate that FB1 and AF, alone and in combination,
      can adversely affect poult performance and health at these dietary
      concentrations.

PMID- 7816727
TI  - Feeding behavior and growth of turkey poults fed larvae of the darkling beetle,
      Alphitobius diaperinus.
AB  - Experiments were conducted to determine the effects of feeding larvae of the
      darkling beetle (lesser mealworm), Alphitobius diaperinus (Panzer)
      [Coleoptera:Tenebrionidae], to turkey poults on poult growth and of beak trimming
      on poult feeding on the larvae. Young turkey poults readily fed on the larvae and
      exhibited reduced growth in the absence of other feed. Poults 3 to 5 d old
      restricted to a diet of only larvae consumed 259 +/- 99 (+/- SD) larvae per poult
      per day and their body weights were significantly lower (mean = 30 g) at the end
      of the 3 d than for poults on starter feed during the same time. After return to
      starter feed for 16 d after feeding on larvae for 3 d, the poults did not
      compensate for the weight loss although weight gains were normal. Poults from 2
      through 10 d of age were given a choice between starter turkey feed and darkling
      beetle larvae. The numbers of larvae consumed per poult per day were: 174 +/- 8
      for Days 2 to 4, 221 +/- 3 for Days 5 to 7, and 189 +/- 80 for Days 8 to 10.
      There was no significant difference between the body weight of poults feeding on
      larvae and starter feed compared with that of poults consuming feed only. In the
      presence of larvae, the mean feed consumption per poult was lower than for poults
      provided with only starter feed. The beetle larvae were 68% crude protein and 21%
      fat (DM basis) and had higher amounts of 18 amino acids than the starter feed.
      Poults that were beak trimmed consumed only about one-third as many larvae as
      poults with intact beaks. Poults (1 to 3 d old) with intact beaks consumed 169 +/
      20 larvae per poult per day; poults with trimmed beaks consumed 58 +/- 23 larvae
      per poult per day.

PMID- 7816728
TI  - Parental effect on the humoral immune response to Escherichia coli and Newcastle
      disease virus in young broiler chicks.
AB  - Genetic and environmental variables influence animal resistance to disease
      infection. In addition, maternal effects were also found in studies with egg-type
      chicken lines. In our laboratory, meat-type chicken lines were divergently
      selected for either early or late maturation of the immune system, based on
      family and individual antibody responsiveness at 10 d of age. The high-antibody
      (HC) and low-antibody (LC) lines differed significantly in the early immune
      response to Escherichia coli, to Newcastle disease virus (NDV) vaccination, and
      to several other immune functions. Reciprocal crosses between the HC and LC lines
      were performed over 2 yr at three different locations. Immune responses to E.
      coli and NDV vaccination provided separate estimates of maternal and paternal
      effects. Dam effect on immune response to E. coli vaccine was significantly
      larger than sire effect; the antibody titer in both reciprocal crosses was
      intermediate between the parental lines, but the mean titer of the HC x LC cross
      was significantly lower than that of the LC x HC cross. Similar, but not
      significant, ranking of crosses was observed for the response to NDV. Evidently,
      the level of the offspring humoral immune response was more a dam than a sire
      effect.

PMID- 7816729
TI  - Efficacy of feeding glucosinolate-extracted crambe meal to broiler chicks.
AB  - Glucosinolates and their breakdown products (nitriles) have long been implicated
      as toxic factors when feeding rapeseed (Brassica napus) meals and crambe (Crambe
      abyssinica) meals to poultry. Accordingly, various methods have been developed to
      remove these compounds from the meals to enhance their value as feed supplements.
      Glucosinolates and nitriles were extracted from commercially processed, defatted
      crambe meal by washing with water or various solvent-water mixtures: 50%
      isopropanol, 50% acetone, or 50% ethanol. In addition, crambe seed was extruded
      and extracted in the laboratory with isopropanol or hexane. Water washing of
      commercially defatted meal proved to be the most effective method of extraction,
      removing 95% of the glucosinolates and nitriles. Meals were fed to 7-d-old
      broiler chicks at 10% of the diet for 14 d. Weight gain decreased (P < .05) in
      most groups; however a greater decrease (P < .01) was observed in birds fed meals
      with high glucosinolate content. Feed intake also decreased (P < .05) in most
      groups; consequently, feed efficiencies were similar for all groups. No changes
      in serum chemistries, triiodothyronine, thyroxine, or tissue lesions were
      associated with glucosinolate or nitrile intake. A relationship (P < .05, r =
      .74) was found between weight gain and glucosinolate intake. No correlation was
      found between feed intake and meal glucosinolate or nitrile concentrations.

PMID- 7816730
TI  - Phytase activity, phosphorus and calcium retention, and performance of single
      comb White Leghorn layers fed diets containing two levels of available phosphorus
      and supplemented with direct-fed microbials.
AB  - The presence of phytase activities in condensed cane molasses solubles (CCMS) and
      CCMS-Lactobacillus (Lacto) were determined. Single Comb White Leghorn layers were
      fed .25 and .45% available P (AP) diets supplemented with CCMS and CCMS-Lacto for
      nine 28-d periods to determine phytase activities of the gastrointestinal (GI)
      tract contents and intestine, liver, and pancreatic tissues, the GI tract pH, the
      P and Ca retention, and layer performance. Six dietary treatments were corn
      soybean (C-S) control, C-S+CCMS, and C-S+CCMS-1,100 mg Lacto/kg diet (ppm) [4.4 x
      10(7) cfu/mg Lacto] each with .25 and .45% AP. The CCMS were used as a carrier
      for the Lacto, and the CCMS and CCMS-Lacto premix were incorporated at 2% of the
      diets. Phytase activity was much higher in CCMS-Lacto premix than in CCMS.
      Phytase activities of the crop contents were higher with the CCMS-Lacto diets
      regardless of the AP level. Intestinal phytase activity was higher with the .45%
      AP CCMS-Lacto diet than the unsupplemented .45% AP diets. Lactobacillus
      supplementation did not stimulate phytase activities in the intestinal contents
      or liver and pancreatic tissues. The pH of the crop and intestinal contents were
      much lower for the Lacto-fed layers than the layers fed unsupplemented diets
      regardless of dietary AP levels. No differences in Ca retentions were observed
      with Lacto supplementation regardless of the dietary AP levels. However, higher P
      retentions were observed with the Lacto supplementation in the .25% AP diet.
      Layers fed .25 and .45% AP Lacto-supplemented diets had lower hen-day egg
      production, poorer feed conversion value, consumed slightly more feed, produced
      less egg mass, and laid larger eggs than the layers fed .25 and .45% AP
      unsupplemented diets. Lacto supplementation to .25% AP diet produced eggs with
      higher specific gravity than the unsupplemented .45% AP diet, but not different
      from unsupplemented .25% AP diet. Layers fed the .25% AP diets had lower BW gains
      then layers fed the .45% AP diets regardless of lacto supplementation. Phytase
      activity was present in the lacto source, and the presence of phytase and Lacto
      supplementation to a .25% AP diet improved P retention in layers.

PMID- 7816731
TI  - Effect of overheating on the nutritional quality of cottonseed meal.
AB  - The effect of overheating on the nutritive value of cottonseed meal (CSM) for
      chicks and protein solubility in .2% KOH was evaluated. One-week-old male chicks
      were assigned to seven diets consisting primarily of corn and unautoclaved
      commercial CSM (expander-solvent extracted) or CSM that had been autoclaved for
      20, 40, 60, 90, or 120 min at 121 C and 105 kPa. The protein level of the diets
      was either 21 or 22%, and FeSO4.7H2O was added to bind any free gossypol in the
      CSM. A control corn-soybean meal diet was included for comparison. A sample of
      full-fat cotton seeds extracted with a mixture of water-acetone-hexane without
      heating (DFCS) was also evaluated. The true digestibility of amino acids in
      cecectomized cockerels was determined for DFCS, three samples of unautoclaved
      commercial CSM, and the commercial CSM that had been autoclaved for 60 or 120
      min. Growth performance of chicks was depressed (P < .05) by feeding CSM
      autoclaved for 40 to 60 min or more. Growth performance of chicks fed CSM diets
      was inferior (P < .05) to that obtained from the corn-soybean meal diet. Protein
      solubility for the unautoclaved commercial CSM was less than for DFCS (70 vs 60%)
      and did not decrease until 90 min of autoclaving. Average amino acid
      digestibility was higher for DFCS than in CSM (85 vs 74%). The mean true
      digestibilities of lysine, methionine, and cystine in the three unautoclaved
      commercial CSM were 64, 72, and 72%, respectively. Digestibilities of amino acids
      in CSM were reduced by 60 and 120 min of autoclaving.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7816732
TI  - Evidence of multiple metabolic routes in vanadium's effects on layers. Ascorbic
      acid differential effects on prepeak egg production parameters following
      prolonged vanadium feeding.
AB  - The development of V toxicity was followed over a 28-d period in 25-wk-old
      Leghorn layers fed 20 mg ammonium metavanadate/kg diet (Days 1 to 14) followed by
      30 mg/kg diet (Days 15 to 28). Then, over a second 28-d period, the responses to
      V and supplemental ascorbic acid (AA) fed at 500 or 1,000 mg/kg diet (Days 29 to
      42) followed by 1,500 or 3,000 mg/kg diet (Days 43 to 56) were examined. Feed
      consumption, egg weight, Haugh units (HU), and BW measurements indicated that the
      response to V was multifactorial, but of differing intensities and time-frames
      for the variables. Haugh units were lowered rapidly (3 d, P < .05) in response to
      V feeding, but HU values decreased only slightly when dietary V was increased to
      30 mg/kg. In contrast, egg production was decreased moderately by 20 mg V/kg and
      a considerable further reduction in egg production resulted from increasing the V
      to 30 mg/kg. Ascorbic acid supplementation differentially affected these
      responses: BW, egg production, and egg weight were improved significantly in the
      V-fed group receiving an AA supplement, as compared with those fed V only. Haugh
      unit values, however, were not improved by AA supplementation in groups receiving
      V. Foam functional properties, which also were changed by V feeding, were not
      corrected by AA feeding. The results suggest that the toxic effects of V are
      mediated through more than one physiological mechanism. One mechanism, which
      includes negative effects on BW, egg production, and egg weight, is responsive to
      the additional reducing equivalents provided by supplemental AA. Another
      mechanism, which is apparent from the effect of V on egg HU values, is not
      ameliorated by AA supplementation after toxicity developed.

PMID- 7816733
TI  - Calcium homeostasis in the laying hen. 1. Age and dietary calcium effects.
AB  - An experiment was carried out to investigate the effects of age of laying hens
      (young = 22 wk vs old = 120 wk) in maintaining Ca homeostasis during periods of
      Ca depletion then repletion with Ca. Plasma Ca and P, tibia breaking strength and
      percentage ash, renal 25-hydroxycholecalciferol-1-hydroxylase (1 alpha
      hydroxylase), and parathyroid hormone (PTH)-stimulated adenylate cyclase
      activities were studied during 28 d of Ca depletion on a .08% Ca diet (LC) and 28
      d of Ca repletion on a 3.75% Ca diet (HC). When laying hens on a HC diet were
      placed on a LC diet, plasma Ca and P, tibia breaking strength and ash percentage,
      and renal PTH-dependent adenylate cyclase activity were significantly depressed,
      but renal 1 alpha-hydroxylase activity was significantly stimulated. These
      changes were greater in the young hens than in the older hens; therefore an
      interaction between age and dietary Ca was found. These changes were of a lesser
      magnitude at 28 d of Ca depletion, probably due to the cessation of egg laying
      and to the desensitization of hormone-mediated function. 1 alpha-Hydroxylase
      activity was significantly less during the repletion period. The age effect was
      most pronounced for 1 alpha-hydroxylase, with the younger birds expressing
      significantly higher activity and ability to respond to hypocalcemia. There was a
      significant increase in kidney weights in Ca-deficient groups at 14 and 28 d of
      Ca depletion. It is concluded that younger hens have greater adaptive responses
      to Ca restriction than do older hens.

PMID- 7816734
TI  - Duodenal calcium uptake, femur ash, and eggshell quality decline with age and
      increase following molt.
AB  - An experiment was conducted to test the hypothesis that the decline in eggshell
      quality over time during egg production, and its improvement after molting,
      paralleled the rate of calcium uptake by the duodenum of the laying hen. In vitro
      duodenal calcium uptake rate and femur ash (percentage of femur weight) were
      determined at 37, 45, 51, 58, 68, and 72 wk of age. Percentage shell and shell
      thickness (millimeters) were determined at 22, 29, 36, 44, 50, 57, and 71 wk of
      age. Molt was induced at 63 wk of age. Three commercial strains DeKalb XL-Link,
      ISA/Babcock B-300V, and Hy-Line W-36 were compared. There were no differences in
      duodenal calcium uptake rate among strains. There was a significant decline (P <
      .01) in duodenal calcium uptake from 408 pmol/mg tissue per min at 37 wk of age
      to 329 pmol/mg per min at 58 wk of age. Femur ash decreased (P < .01) from 50.8%
      at 37 wk of age to 47.6% at 58 wk of age. Percentage shell and shell thickness
      declined (P < .01) from 9.79% and .403 mm at 22 wk of age to 8.88% and .373 mm at
      57 wk of age, respectively. After the induced molt, duodenal calcium uptake
      increased (P < .01) to 402 pmol/mg tissue per min, and percentage shell and shell
      thickness increased (P < .01) to 10.23% and .389 mm, respectively. Duodenal
      calcium uptake increased immediately postmolt, whereas femur ash did not increase
      until 72 wk of age (P < .01).

PMID- 7816735
TI  - Morphological observations of turkey (Meleagris gallopavo) spermiophages
      maintained in tissue culture.
AB  - Spermiophages were isolated from turkey semen using Percoll gradient
      centrifugation, cultured in Roswell Park Memorial Institute 1640 medium at room
      temperature, and characterized by transmission electron microscopy. After 1 to 2
      h, the cells enlarged and developed numerous motile mitochondria. Over time, the
      mitochondria appeared to increase in number and were released into the
      extracellular medium. Few mitochondria were observed in spermiophages from fresh
      semen. However, there was an apparent increase in the number and size of
      mitochondria after Percoll isolation, which was more pronounced in cultured
      spermiophages. Over a period of 3 h in culture, many spermiophages became
      engorged with mitochondria, which subsequently appeared to be released as blebs
      pinched off from the surface. The release of mitochondria resulted in
      spermiophages with large, empty vacuoles, although their remaining cytoplasm was
      engorged with mitochondria. Many free mitochondria were present in the medium.
      The results of the current research suggest that isolating and culturing turkey
      spermiophages elicit mitochondrial biogenesis, which proceeds unabated until the
      cells are engorged with and release numerous mitochondria. This may be due to
      conditions under which the spermiophages were cultured or to
      nonhistocompatibility of these cells in pooled semen.

PMID- 7816736
TI  - Relationship between shell porosity, shell thickness, egg weight loss, and
      embryonic development in Japanese quail eggs.
AB  - Japanese quail eggs that hatched (H) or pipped (PIP) exhibited less weight loss
      through 15 d of incubation than did eggs that died late (LD), whereas eggs
      containing early dead (ED) embryos exhibited the greatest weight loss. The pore
      concentration at the large end of each egg was greatest in H eggs when compared
      with all other types. The pore concentration at the equator was greatest in H
      eggs and least in the eggs of the ED embryos. All other egg types lay
      statistically between these two types with regard to equator porosity. The small
      end pore concentration was similar in H, INF, and LD eggs and in the LD, PIP, and
      ED eggs. The least number was exhibited by the ED eggs and most by the H eggs.
      The thinnest shells at the small end were exhibited by H eggs, whereas thicker
      small end shells were exhibited by ED, LD, and PIP egg types. No differences were
      observed at the large end or equator. The data suggest that ED eggs exhibit
      excessive weight loss even though shell porosity was lower and shell thickness
      was similar to other egg types. This suggests that some functional component of
      the egg such as the shell membrane or albumen may contribute to this excessive
      weight loss. A similar statement can be made for LD eggs, which experienced
      greater weight loss through 15 d than did PIP or H eggs.

PMID- 7816737
TI  - Screening chickens for endogenous virus ev21 viral element by the polymerase
      chain reaction.
AB  - The molecular architecture of the sex-linked late-feathering region of the
      chicken genome is still poorly defined. Current evidence points to a strong
      association between the presence of the endogenous viral element ev21 and the
      late-feathering phenotype. However, analysis at the molecular level has
      demonstrated that this is not a simple case of insertional mutagenesis. Instead,
      the structure of the region of the chicken genome containing the feathering locus
      is complex and variable between and within lines of chickens. Significant clues
      to the molecular structure of this genomic region can be obtained by analyzing
      rare and revertant genotypes. However, searching for rare genotypes can only be
      carried out effectively using quick screen methodology. This paper describes a
      quick, polymerase chain reaction-based test for ev21 that facilities the search
      for rare genotypes.

PMID- 7816738
TI  - A comparison of two methods for isolation of Salmonella from poultry litter
      samples.
AB  - Two methods were compared to determine their ability and efficiency in detecting
      Salmonella in poultry litter samples. Method 1 consisted of pre-enrichment in
      buffered peptone water (BPW), selective motility enrichment in Modified Semisolid
      Rappaport Vassiliadis (MSRV) agar, and plating onto MacConkey (MC) agar. Method 2
      employed tetrathionate brilliant green (TBG) broth and plating on brilliant green
      agar with novobiocin (BGAN) and on xylose lysine tergitol 4 (XLT4) agar. Method 1
      resulted in a significantly higher isolation rate, was cheaper, and was less
      labor intensive.

PMID- 7816739
TI  - Effects of acute and chronic treatment with trazodone, an antidepressant, on the
      sleep-wake activity in rats.
AB  - Rats were treated with trazodone (2.5 or 10 mg kg-1) twice a day (at light and
      dark onset) for 11 days, after chronic injection of physiological saline. The
      sleep-wake activity was recorded for 24 h on the baseline day (saline), on
      trazodone days 1, 5 and 11, and also on day 12, when physiological saline was
      injected again (withdrawal day). Trazodone administration increased non-REM
      sleep. The enhancement of non-REM sleep was dose-related and more pronounced
      during the dark cycle. The promotion of non-REM sleep was enhanced during the
      chronic treatment. There were no consistent changes in REM sleep. Spectral
      analysis of the EEG revealed an increase in slow-wave activity after
      administration of the high dose (10 mg kg-1) of the drug. It is concluded that
      trazodone, a clinically effective antidepressant, has a non-REM sleep-promoting
      effect. It is speculated that the promotion of sleep by trazodone may be mediated
      by serotonergic mechanisms.

PMID- 7816740
TI  - Ketamine protects acetylcholinesterase against inhibition by propoxur and phoxim.
AB  - In the present study the effect of ketamine on the contractions caused by
      propoxur and phoxim on the isolated guinea pig ileum was investigated. Ketamine
      was found able to inhibit in a concentration-dependent manner the contractile
      responses of the ileum to propoxur and phoxim, while it did not significantly
      modify the contractions induced by acetylcholine. Propoxur and phoxim augmented
      the contractile responses induced by acetylcholine in the presence of
      acetylcholinesterase. This augmentation was prevented by ketamine, in a
      concentration-dependent manner. These findings suggest that ketamine inhibits the
      contractile effect of propoxur and phoxim on the guinea pig ileum and this
      inhibition seems to be associated with the protection of acetylcholinesterase
      against the action of these two compounds.

PMID- 7816741
TI  - Gastric lipid peroxidation, glutathione and calcium channel blockers in the
      stress-induced ulcer model in rats.
AB  - The antiulcer activity of verapamil and its analogues devapamil and gallopamil
      was studied. All three drugs reduced cold-restraint stress-induced ulcer
      development. Gallopamil almost abolished gastric ulcers. Verapamil prevented the
      increase in gastric lipid peroxidation (LP) due to stress. On the other hand,
      devapamil and gallopamil increased gastric lipid peroxidation and decreased
      glutathione levels. This effect may be attributed to the increase in oxygen
      supply due to possible effective vasodilation at gastric mucosa. The second part
      of this study revealed that stress-induced gastric ulcers in rats rapidly and
      spontaneously heal and disappear within 24 h. During recovery, gastric LP
      decreased and glutathione levels increased within 12 h after the withdrawal of
      stress, preceded by an initial reduction in glutathione. After 72 h, an
      unexplained increase in gastric LP and a decrease in glutathione were observed.
      Treatment with verapamil, devapamil and gallopamil promoted healing, gallopamil
      being again the most effective. Their effects on gastric LP and glutathione
      levels are in accordance with the results of pretreatment experiments. In
      conclusion, devapamil and gallopamil are effective antiulcer agents against
      stress-induced ulcers, but unlike verapamil, antioxidant activity does not seem
      likely to be among their mechanisms of action.

PMID- 7816742
TI  - Protective effects of BAY U 3405, a thromboxane A2 receptor antagonist, in
      endotoxin shock.
AB  - The present study was designed to investigate the effects of BAY U 3405, a new
      thromboxane A2 (TxA2) receptor antagonist, in endotoxin shock. Endotoxin shock
      (ES) was induced in male rats by an i.v. injection of Salmonella enteritidis
      lipopolysaccharide (LPS; 20 mg kg-1). LPS administration caused animal death
      (survival = 0%, 48 h after endotoxin challenge), systemic hypotension, depressed
      phagocytosis and increased blood levels of TNF-alpha, TxB2 and 6-keto-PGF1 alpha,
      reduced white blood cell (WBC) count (ES = 5.9 +/- 1 x 10(3) mm-3; CTRL = 13.4 +/
      5 x 10(3) mm-3) and enhanced myeloperoxidase (MPO) activity, studied as a
      quantitative means for assessing leukocyte accumulation, in the ileum (ES = 0.24
      +/- 0.7 U g-1 fresh tissue; CTRL = 0.13 +/- 0.04 U g-1 fresh tissue), in the
      heart (ES = 0.41 +/- 0.1 U g-1 fresh tissue; CTRL = 0.16 +/- 0.08 U g-1 fresh
      tissue) and in the lung (ES = 0.68 +/- 0.11 U g-1 fresh tissue; CTRL = 0.19 +/-
      0.05 U g-1 fresh tissue). Furthermore, endotoxin administration produced
      characteristic damage of the gastric mucosa consisting of haemmorrhagic
      infiltrates. BAY U 3405 (30 mg kg-1 i.v., 30 min before endotoxin challenge)
      increased survival rate (45% survival rate 48 h after endotoxin challenge),
      reduced hypotension, decreased TNF-alpha levels in serum, enhanced phagocytic
      activity (ES = 25.6 +/- 1.9%, BAY U 3405 = 45.9 +/- 0.4%, P < 0.001) and lowered
      MPO activity in the ileum (0.14 +/- 0.05 U g-1 fresh tissue), in the heart (0.18
      +/- 0.08 U g-1 fresh tissue) and in the lung (0.44 +/- 0.09 U g-1 fresh tissue).
      Finally, the gastric alterations were significantly reduced in rats pretreated
      with BAY U 3405. These data suggest that this thromboxane receptor antagonist
      might be a useful drug in shock conditions.

PMID- 7816743
TI  - Non-invasive haemodynamic study in hypertensive subjects after treatment with
      verapamil slow release.
AB  - Aim of this study is to investigate the haemodynamic effects, after the short and
      long-term antihypertensive treatment. After a wash-out period and a placebo
      treatment period, 30 hypertensive patients received verapamil SR (slow release,
      240 mg o.d.) for 30 days. A significant decrease in systolic and diastolic blood
      pressure was obtained already 4 h after the first administration of verapamil; it
      was more evident and persistent throughout the study. No significant changes of
      heart rate or PR interval in ECG were observed. A significant decrease in total
      vascular resistances, both supine and upright, was evident already 4 h after the
      drug intake and observed throughout the study. The major effect was obtained
      after one month. No significant changes of cardiac output, cardiac index and
      stroke volume were recorded. Furthermore, plasma verapamil levels were measured
      to confirm that the haemodynamic effects are obtained by low drug concentrations.
      The present study provides evidence that the antihypertensive effect of
      verapamil, whose mechanism is the reduction of total vascular resistances, is
      progressive, long acting and achieved by low plasma levels, when slow release
      formulation is considered.

PMID- 7816744
TI  - Functional comparison between nuvenzepine and pirenzepine on different guinea pig
      isolated smooth muscle preparations.
AB  - The antimuscarinic agents nuvenzepine and pirenzepine were tested on four guinea
      pig isolated smooth muscle preparations in order to better investigate the
      existence of differences in the functional activities of such antagonists, as
      suggested by previous reports. The effects of both compounds were compared to
      those of atropine. Nuvenzepine showed a four-fold higher affinity than
      pirenzepine in competitively antagonizing acetylcholine-induced contractions on
      isolated ileal musculature (pA2 = 7.08 +/- 0.15) and on longitudinal ileum
      dispersed cells (pA2 = 7.11 +/- 0.19). By contrast, unlike pirenzepine which was
      ineffective, nuvenzepine inhibited histamine-induced ileal motor activity in a
      dualistic manner, behaving as an irreversible competitive H1 antagonist (pA2 =
      5.02 +/- 0.11). Nuvenzepine was almost equipotent to pirenzepine in competitively
      preventing bethanechol-induced gall-bladder contractions (pA2 = 7.23 +/- 0.16)
      and it displayed a four-fold higher potency than pirenzepine in blocking vagal
      stimulated tracheal constrictions (pIC50 = 6.77 +/- 0.06). Both compounds were
      definitely less potent than atropine. On the whole, these findings indicate that,
      on the selected preparations, nuvenzepine substantially shares the antimuscarinic
      properties of pirenzepine but it is also endowed with a (weak) H1-blocking
      action. Furthermore, based on some observations, the presence in gallbladder
      smooth muscle of muscarinic receptors distinguishable from those of ileum could
      be speculated.

PMID- 7816746
TI  - Antiulcer drugs and gastric mucosal blood flow.

PMID- 7816745
TI  - Age-related alterations of skeletal muscle metabolism by intermittent hypoxia and
      TRH-analogue treatment.
AB  - The characteristics of the energy metabolism were evaluated in the gastrocnemius
      muscle from 3- and 24-month-old rats in normoxia or subjected to either mild or
      severe chronic (4 weeks) intermittent normobaric hypoxia. Furthermore, 4-week
      treatment with saline or the TRH-analogue posatireline was performed. The
      muscular concentration of the following metabolites related to the energy
      metabolism was evaluated: glycogen, glucose, glucose 6-phosphate, pyruvate,
      lactate, lactate-to-pyruvate ratio; citrate, alpha-ketoglutarate, succinate,
      malate; aspartate, glutamate, alanine; ammonia; ATP, ADP, AMP, creatine
      phosphate; energy charge potential. Furthermore the maximum rate of the following
      muscular enzymes was evaluated: hexokinase, phosphofructokinase, pyruvate kinase,
      lactate dehydrogenase; citrate synthase, malate dehydrogenase; total NADH
      cytochrome c reductase; cytochrome oxidase. The age-related decrease in muscular
      glucose 6-phosphate, pyruvate and alanine concentrations and increase in citrate
      concentration were consistent with the age-related decreased hexokinase and
      increased citrate synthase activities. Ageing was characterized by a decrease in
      muscular creatine phosphate concentration, while the energy mediators and the
      energy charge potential were unchanged. The chronic (4 weeks) intermittent
      normobaric mild and severe hypoxia-induced alterations of the components in the
      anaerobic glycolytic pathway, tricarboxylic acid cycle and energy storage, that
      were magnified in the skeletal muscle from the oldest animals. The effect of the
      chronic treatment with the TRH-analogue posatireline suggests that the action of
      central nervous system-acting drugs could also be related to their direct
      influence on the muscular biochemical mechanisms related to the energy
      transduction.

PMID- 7816747
TI  - Effects of chloroquine on pentylenetetrazol-induced convulsions in mice.
AB  - The effects of chloroquine pretreatment were investigated on pentylenetetrazol
      induced clonic-tonic convulsions in mice. The results demonstrated that lower
      doses of chloroquine (1.0-5.0 mg kg-1) significantly induced a delay in onset
      time to the clonic component of convulsions and reduced the incidence of the
      tonic phase of convulsions and mortality. In contrast, at a higher dose range
      (10.0-50.0 mg kg-1) chloroquine had opposite effects. This study points out the
      biphasic action of chloroquine on clonic-tonic PTZ convulsions and its
      preferential effect against the tonic phase of convulsions.

PMID- 7816748
TI  - Investigation of the distribution of EAB 515 to cortical ECF and CSF in freely
      moving rats utilizing microdialysis.
AB  - A freely moving rat model was developed to study the CNS distribution of EAB 515
      (S-alpha-amino-5-phosphonomethyl[1,1'-biphenyl]-3-propanoic acid). Microdialysis
      (MD) in the frontal cortex (FrC) and in the lateral ventricle (LV) of the rat
      brain was performed to measure the levels of EAB 515 in the cortical
      extracellular fluid (ECF) as well as in the cerebrospinal fluid (CSF). The
      femoral artery and femoral vein were cannulated for serial blood sampling and
      intravenous (i.v.) drug administration, respectively. EAB 515 was also
      administered via the intracerebroventricular (icv) route in a cross-over
      experiment. The in vivo recovery of EAB 515 across the MD probes was determined
      by simultaneous retrodialysis (RD) performed using a hydroxylated analog of EAB
      515, as the RD calibrator (RDC). An extremely sensitive and selective on-line
      HPLC system with native fluorescence detection was developed for the simultaneous
      analysis of EAB 515 and RDC in microdialysate samples from rat CSF and cortical
      ECF. Unbound concentrations of EAB 515 in the rat plasma were determined by
      direct injection of plasma ultrafiltrate onto the HPLC column. The validity of
      the use of RDC as the RD calibrator was demonstrated by comparing the results of
      zero-net flux (ZNF) analysis simultaneously in some experiments. After constant
      rate i.v. infusion in rats (n = 12) for 900 min, the average (S.D.) ratio of the
      levels of EAB 515 in the CSF to those in plasma (Ccsf.iv/Cp) was determined to be
      17.7 (7.8)% and that in the cortex relative to plasma (Ccortex.iv/Cp) was 8.3
      (4.8)%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7816749
TI  - Effect of moisture sorption on tabletting characteristics of spray dried (15%
      amorphous) lactose.
AB  - Spray dried (15% amorphous) lactose absorbs moisture when exposed to humidity. At
      57% relative humidity (RH), the moisture uptake was 1.5%. It is suggested that
      the moisture is preferentially taken up in the amorphous regions, thereby
      increasing the actual moisture content in the amorphous parts up to 10%. The
      moisture uptake reduced the glass transition temperature below the operating
      temperature and thereby transformed the amorphous regions from a glassy to a
      rubbery state, setting up conditions for crystallisation of the lactose.
      Compaction of dry spray dried lactose led to a relatively low initial tablet
      strength. However, when pre-exposed to 57% RH for a short time period (2 to 4
      hours) before compaction, the initial tablet strength increased markedly. This
      was due to moisture uptake which resulted in a higher molecular mobility of the
      amorphous spray dried lactose, and to an increase in plastic flow. Post
      compaction storage of tablets containing amorphous regions of spray dried lactose
      at 57% RH resulted in an increased tablet strength after 4 hours due to
      crystallisation. Spray dried lactose exposed to 57% RH for more than 6 hours
      before compaction led to the lowest initial tablet strength. Crystallisation of
      the amorphous regions of the spray dried lactose occurred before tabletting. No
      increase in tablet strength was noted on post compaction storage for these
      tablets.

PMID- 7816750
TI  - Study on pulmonary delivery of salmon calcitonin in rats: effects of protease
      inhibitors and absorption enhancers.
AB  - Effects of protease inhibitors and absorption enhancers on the absorption of
      salmon calcitonin (sCT) were evaluated after intratracheal coadministration to
      rats using the plasma Ca level as an index. Remarkable absorption enhancement
      could be attained with unsaturated fatty acids such as oleic acid and
      polyoxyethylene oleyl ether (absorption enhancers) and with chymostatin,
      bacitracin, potato carboxypeptidase inhibitor and phosphoramidon (protease
      inhibitors). sCT degrading enzymes had four times higher activity per total
      protein in membrane fraction of lung homogenates than the activity in cytosol
      fraction. These enzymes are thought to be serine proteases and metalloenzymes
      from the in vitro action profile of protease inhibitors. A good correlation
      between the in vitro activity of protease inhibitors and the in vivo enhancing
      effect on sCT activity suggested that membrane enzymes are responsible for the
      inactivation of sCT. Metabolic degradation and low permeability of sCT may be
      possible barriers to the absorption of sCT.

PMID- 7816751
TI  - Effect of epidermal growth factor on Cu, Zn-superoxide dismutase expression in
      cultured fibroblasts from rat skin.
AB  - The effects of epidermal growth factor (EGF) on Cu, Zn-superoxide dismutase (SOD)
      in cultured fibroblasts from rat skin exposed to superoxide anions were studied.
      Cross-linking of [125I]hEGF using disuccinimidyl suberate and immunoblot analysis
      using anti-EGF receptor antibody to crude plasma membrane fractions of
      fibroblasts showed that a 170 kDa EGF receptor protein was present on the
      membrane, as in A431 cells which over express a specific EGF receptor. The
      cytosolic SOD enzyme activity in fibroblasts exposed to superoxide anions 24 h
      after treatment with EGF plus nafamostat (NM), a potent protease inhibitor, was
      increased 1.6-fold compared to control-treated cells. Treatment with either EGF
      or NM alone, evoked little increase in SOD enzyme activity. The increase in Cu,
      Zn-SOD protein levels corresponded to the increase in cytosolic SOD enzyme
      activity in fibroblasts. The Cu, Zn-SOD mRNA level in fibroblasts treated with
      EGF plus NM at 3 and 6 h was higher than that of the control. Additionally,
      levels of [125I]hEGF degradation products released into the medium from
      fibroblasts exposed to superoxide anions were significantly reduced in the
      presence of NM. These results suggest that the stabilization of EGF by NM in
      culture is an important factor in the expression of its effects, and that EGF
      induces Cu, Zn-SOD expression by accelerating transcription of the Cu, Zn-SOD
      gene in cells, resulting in their protection from the effects of superoxide anion
      radicals.

PMID- 7816752
TI  - Transepithelial transport of tyramine across filter-grown MDCK cells via a poly(D
      lysine) carrier.
AB  - In order to investigate the advantage of using membrane-adsorptive carriers to
      mediate drug transport across epithelial tissue, we have prepared disulfide- and
      thioether-linked conjugates of tyramine (tyn) as a model drug to a cationic,
      nondegradable carrier, poly(D-lysine) (PDL). The transport properties were
      evaluated using microporous filter-grown Madin-Darby canine kidney (MDCK, strain
      I) epithelial cells, and we have determined that: (a) the [125I]tyn-SS-PDL
      conjugate predominantly transported [125I]tyn in the apical-to-basal direction
      (20-fold greater transport vs. basal-to-apical); (b) [125I]tyn-SS-PDL elicits a
      10-fold greater degree of [125I]tyn transport than [125I]tyn-S-PDL, thus
      demonstrating the importance of the reducible disulfide linkage for [125I]tyn
      transport to occur; (c) 125I-radioactivity recovered in the basal media was
      determined to be 95% [125I]tyn-containing small molecules, thus demonstrating the
      release of [125I]tyn from its PDL carrier; (d) the apical addition of an anionic
      species, heparin, completely blocks apical-to-basal transport of [125I]tyn,
      indicating the importance of PDL-mediated binding to the apical membrane for
      transport to occur; (e) apical-to-basal transport proceeds via non-lysosomal
      pathways, as lysosomal inactivation by NH4Cl exposure does not inhibit transport,
      and (f) the addition of a membrane-impermeable inhibitor of disulfide reduction,
      bisdithionitrobenzoic acid (DTNB), to the apical media inhibits transport by
      approximately 70%, indicating the importance of apically-localized disulfide
      reducing reactions for transport of [125I]tyn. Pulse-chase studies indicate that
      there is no paracellular leakage of conjugate, and the ratio of recycled:membrane
      associated:transported [125I]tyn fragment following chase is 4:2:1.

PMID- 7816754
TI  - Effect of ultrafilterable platinum concentration on cisplatin and carboplatin
      cytotoxicity in human tumor and bone marrow cells in vitro.
AB  - The importance of the ultrafilterable platinum (fPt) fraction of cisplatin (CDDP)
      and carboplatin (CBDCA) for cytotoxicity and myelotoxicity was studied in vitro.
      By incubating CDDP or CBDCA with fetal calf serum (FCS) various fractions of fPt
      were prepared and determined by atomic absorption spectroscopy. A relation of %
      fPt fraction and incubation time (h) of 87e-0.1123t (r = -0.99) and 101e-0.0087t
      (r = -0.99) were determined for CDDP and CBDCA, respectively. Cytotoxicity in the
      human small cell lung carcinoma cell line GLC4 and fPt fraction were closely
      related for CDDP (r = 0.99) and for CBDCA r = 0.97). However, at a similar fPt
      fraction the concentrations inhibiting cell survival by 50% (IC50) of CBDCA
      exceeded that of CDDP by a factor of 10-18 with 4 h exposure and a factor of 5
      with continuous exposure. Tested in the range of peak concentrations in plasma of
      patients and at a clinically relevant fPt fraction of 10%, CDDP was not toxic for
      human bone marrow cells in the CFU-GM assay, whereas it was toxic at fPt
      fractions of 50% and 90%. However, CBDCA was myelotoxic at a (clinically
      relevant) fPt fraction of 50%, and also at 75% and 90%. The use of different fPt
      fractions, produced by the incubation method described in this study, permits the
      study of platinum drugs in vitro while approximating in vivo conditions might be
      used to evaluate myelotoxicity of new platinum drugs prospectively. For CDDP and
      CBDCA the fraction fPt determines cytotoxicity on tumor cells, and their
      different fPt fraction in patients account at least partly for their difference
      in myelotoxicity.

PMID- 7816755
TI  - Preparation and characterization of novel poly(methylidene malonate 2.1.2.)-made
      nanoparticles.
AB  - Poly(methylidene malonate 2.1.2.) (PMM 2.1.2.) nanoparticles were prepared in
      phosphate buffer through emulsion polymerization of monomeric units; the kinetics
      of the reaction was monitored by spectrophotometry at 400 nm. Average
      nanoparticle sizes, molecular weights, and biodegradability of this potential
      drug carrier were determined under various conditions. As previously demonstrated
      for other similar monomers, i.e. IHCA or IBCA, pH influenced the physico-chemical
      characteristics of the nanoparticles obtained. Ethanol release from the ester
      bearing side chains indicated that the polymers were susceptible to hydrolysis
      when incubated in basic pH or in rat plasma. A secondary degradation pathway,
      yielding formaldehyde through a reverse Knoevenagel's reaction, was minimal.
      Cytotoxicity studies of this new vector, in vitro, against L929 fibroblast cells
      demonstrated that PMM 2.1.2. nanoparticles were better tolerated than other
      poly(alkylcyanoacrylate) (PACA) carriers. Pharmacokinetic studies were also
      carried out to observe the fate of 14C-labelled PMM 2.1.2. nanoparticles after
      intravenous administration to rats. Forty eight hour post-injection, more than
      80% of the radioactivity was recovered in urine and faeces. The body distribution
      of the polymer was estimated by measuring the radioactivity associated with
      liver, spleen, lung and kidneys. Five minutes after injection, a maximum of 24 +/
      2% of the total radioactivity was detected in the liver and less than 0.4% in
      the spleen. The liver-associated radioactivity decreased according to a biphasic
      profile and less than 8% of the total radioactivity remained after 6 days.

PMID- 7816753
TI  - Brain delivery of biotin bound to a conjugate of neutral avidin and cationized
      human albumin.
AB  - The delivery of pharmaceuticals through the brain capillary endothelial wall,
      which makes up the blood-brain barrier (BBB) in vivo, may be facilitated by
      conjugation of therapeutics to brain drug delivery vectors. Since cationized
      albumin has been shown to undergo absorptive-mediated transcytosis through the
      BBB in vivo, cationized human serum albumin (cHSA) is a potential brain drug
      delivery vector in humans. Conjugation of biotinylated therapeutics to brain drug
      delivery vectors is facilitated by the preparation of vector/avidin conjugates.
      Therefore, the present studies describe the preparation of a cHSA-avidin
      conjugate and the delivery of 3H-biotin bound to this conjugate through the BBB
      in vivo in anesthetized rats. Since the cationic nature of avidin (AV)
      accelerates the removal of avidin-based conjugates from blood in vivo, the
      present studies also describe the preparation and the pharmacokinetics of 3H
      biotin bound to a conjugate of cHSA and neutral avidin (NLA). The bifunctional
      nature of the conjugate was retained: the cHSA/NLA conjugate contained 2.8 to 6.8
      biotin binding sites per conjugate, and the BBB permeability-surface area (PS)
      product for 3H-biotin bound to cHSA/NLA was at least 7-fold greater than the BBB
      PS product for 3H-biotin bound to a conjugate of NLA and native HSA (nHSA). The
      systemic clearance of the cHSA conjugate was reduced 10-fold by the use of NLA as
      opposed to AV. The increased area under the plasma concentration curve (AUC) of
      the cHSA-NLA conjugate correlated with an increase in brain delivery of 3H-biotin
      as compared to the brain delivery achieved with the cHSA/AV conjugate.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7816756
TI  - Controlled ocular timolol delivery: systemic absorption and intraocular pressure
      effects in humans.
AB  - Timolol eyedrops may cause systemic side-effects in glaucoma patients due to
      absorption of the drug into systemic circulation. In a previous study, timolol
      concentrations in plasma were reduced if timolol was administered in ocular
      inserts instead of eyedrops. We compared the intraocular pressure lowering effect
      and systemic absorption of timolol inserts to those of 0.5% timolol eyedrops in
      humans. Inserts of silicone tubing released 90.3 +/- 13.9 micrograms of timolol
      in 24 hours in vivo. Timolol inserts afforded similar decreases in intraocular
      pressure in open-angle glaucoma patients as did b.i.d. eyedrops, but produced
      lower peak timolol concentrations in plasma, 0.70 +/- 0.10 ng/ml and 0.24 +/-
      0.05 ng/ml, respectively. After eyedrops, peak concentrations were achieved at
      15.0 +/- 2.2 min, while application of an insert resulted in a delayed peak (tmax
      = 623 +/- 195 min). The insert resulted in a higher systemically absorbed
      fraction of the timolol dose than the eyedrop, but the peak timolol concentration
      and daily absorbed amount of timolol were decreased. The release rate of timolol
      from the inserts in vivo was only slightly less than that in vitro. Silicone
      devices are useful for clinical testing of controlled delivery properties of
      ocular drugs.

PMID- 7816757
TI  - Effects of cholesterol and cholesteryl oleate on lipolysis and liver uptake of
      triglyceride/phosphatidylcholine emulsions in rats.
AB  - Emulsions composed of soy bean triglyceride (TG), egg yolk phosphatidylcholine
      (PC), cholesterol (Chol) or cholesteryl-oleate (CO), labeled with a cholesteryl
      ether (3H-CHE) and a triglyceride (14C-TO), were injected into rats. 14C-TO was
      removed from plasma faster than 3H-CHE. The 14C-labeled moiety is cleaved by
      digestion of the TG in the emulsion in plasma and is removed to the endothelial
      cells (lipolysis). In contrast, the 3H-label remains stably associated and
      represents circulating emulsion particles. The majority (90%) of the 3H-label
      disappearing from the plasma accumulated in the liver for all types of emulsions.
      On the basis of these observations, the lipolysis and the removal of emulsion
      particles to organs (mainly liver) were determined: 30 mole percent of
      cholesterol (Chol) at the TG-PC emulsion surface markedly retarded organ uptake,
      but the effect on lipolysis was rather small; 20 mole percent of cholesteryl
      oleate (CO) in the TG-PC emulsion cores delayed both organ uptake and lipolysis,
      and induced a rapid increase in organ uptake rate after the initial delay
      accompanying the gradual progress of lipolysis. Lipolysis led to the enrichment
      of the cores with CO. Replacement of the core TG by CO, however, induced strong
      suppression of the liver uptake. These results show that the lipid composition at
      both surface and core of emulsion particles is a crucial factor in metabolism in
      the rat.

PMID- 7816758
TI  - A convective-diffusion model for dissolution of two non-interacting drug mixtures
      from co-compressed slabs under laminar hydrodynamic conditions.
AB  - A numerical convective-diffusion dissolution model has been extended to describe
      dissolution of two neutral non-interacting drugs co-compressed in a slab
      geometry. The model predicted the experimental dissolution rates of
      naproxen/phenytoin mixtures and hydrocortisone/nitrofurantoin mixtures quite
      accurately, except for phenytoin in the naproxen/phenytoin mixture at low weight
      proportions. A non-linear dependence of dissolution rate on weight proportion
      with a positive deviation from linearity was observed. An increase in flow rate
      increased the dissolution rate and the cube-root dependency of dissolution rate
      on the flow rate for a given weight proportion of the component in the slab, as
      proposed earlier by Shah and Nelson for pure compounds, was also observed here,
      suggesting that the changes in dissolution profile were caused by changes in
      surface area only. As expected from the model an increase in particle size of the
      powders used to make the slab decreased the dissolution rate. This was explained
      by an increase in the average length of the component resulting in a bigger
      'carryover' of material from one section of the component in the slab to the next
      section of the same component, due to convection, and hence lower flux.

PMID- 7816760
TI  - Solid-state emulsions: evaluation by 1H and 13C solid-state nuclear magnetic
      resonance.
AB  - The molecular environment of sucrose and mineral oil within sucrose and mineral
      oil solid state emulsions was investigated by NMR techniques. The 13C and 1H
      chemical shifts of sucrose and mineral oil to those observed in solid state
      emulsions (comprised of sucrose and mineral oil) were equivalent, indicating that
      the local structure of sucrose is unaffected by the presence of mineral oil in
      the solid-state emulsion. Cross-polarization, magic angle spinning 13C (CP-MAS)
      in conjunction with single-pulse studies indicated that the 1H-13C dipole-dipole
      interactions are very weak, i.e., mineral oil is highly mobile. Spinning side
      bands were observed, however, in 1H single-pulse, magic angle spinning (SPMAS)
      spectra of the solid-state emulsion, indicating that the mineral oil has solid
      properties. Although the mineral oil was shown to be highly mobile, it also
      appears to be constrained or included by the sucrose.

PMID- 7816759
TI  - Iontophoresis of a model peptide across human skin in vitro: effects of
      iontophoresis protocol, pH, and ionic strength on peptide flux and skin
      impedance.
AB  - This study deals with effects of electrical (current density, frequency and duty
      cycle) and chemical (buffer pH and ionic strength) conditions on the flux of the
      octapeptide, 9-desglycinamide, 8-arginine-vasopressin (DGAVP), through dermatomed
      human skin. A pulsed constant current was applied during iontophoresis. The anode
      faced the anatomical surface of the skin samples inside the diffusion cells. The
      resistive and capacitative components of the equivalent electrical circuit of
      human skin could be calculated by fitting the voltage response to a bi
      exponential equation. The skin resistance prior to iontophoresis varied between
      20 and 60 k omega.cm2. During iontophoresis a decrease of skin resistance and an
      increase of the series capacitances was observed, which were most pronounced
      during the first hour of iontophoresis; thereafter both quantities gradually
      levelled off to an apparent steady state value. The reduction of the resistance
      during iontophoresis increased non-linearly with increasing current density
      between 0.013-0.64 mA.cm-2. The steady state resistance and capacitances did not
      vary significantly with frequency and duty cycle of the current pulse. There was
      no pH dependence of skin resistance at steady state. Between pH 4 and 10, the
      steady state peptide flux had a bell-shaped pH-dependence with a maximum of 0.17
      nmol.cm-2.h-1 at pH 7.4, which is close to the I.E.P. of the peptide. Lowering
      the ionic strength from 0.15 to 0.015 M NaCl increased the steady state flux at
      pH 5 and pH 8 by a factor 5 to 0.28 +/- 0.21 and 0.48 +/- 0.37 nmol.cm-2.h-1,
      respectively. Together these observations suggested that DGAVP is transported
      predominantly by volume flow.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7816761
TI  - Hindered diffusion of polar molecules through and effective pore radii estimates
      of intact and ethanol treated human epidermal membrane.
AB  - The in vitro passive transport of urea, mannitol, sucrose and raffinose across
      intact and ethanol treated human epidermal membrane was investigated. The intent
      of this study was to characterize the barrier properties and permeation pathways
      of these membranes for polar permeants under passive conditions. Based upon the
      relative permeabilities of these four solutes and hindered diffusion theory, the
      experimental data was adequately modeled for both membrane systems according to
      permeation through a porous membrane. Effective pore radii estimates for intact
      human epidermal membrane fell between 15 A to 25 A while similar estimates fell
      compactly between 15 A to 20 A for ethanol treated human epidermal membrane.
      Similarities between the relative permeabilities of human epidermal membrane for
      the four permeants studied and the relative permeabilities of these same
      permeants through ethanol pretreated human epidermal membrane indicate that
      significant similarities exist between the permeation pathways for both membrane
      systems. The results of this study have important implications for transdermal
      drug delivery in general and more specifically for strategies of designing
      effective chemical permeation enhancement systems.

PMID- 7816762
TI  - Liquid scintillation spectrometry of 5-fluorouracil in cervical tissue following
      in vitro surface application of a bioadhesive cervical patch.
AB  - The potential use of bioadhesive technology for the treatment of cervical
      intraepithelial neoplasia was investigated. A cervical patch was designed
      containing 5-fluorouracil in a bioadhesive matrix and polyvinyl chloride as the
      backing layer. The concentration of 5-fluorouracil at specified tissue depths
      from the cervical surface was determined in vitro in relation to the ability of
      the drug to reach precancerous foci in cervical crypts up to 4 mm below the
      tissue surface. Thus, tissue was exposed to drug-loaded patches spiked with 5
      fluorouracil-6-3H and subsequently sectioned to obtain tissue slices at different
      depths. The concentration of 5-fluorouracil was determined by liquid
      scintillation spectrometry. Drug penetration into cervical tissue exceeded a
      depth of 5.5 mm. Furthermore, the concentration in the tissue depended on the
      drug loading in the patch. Patches containing 10 and 20 mg of 5-fluorouracil
      produced a linear drug gradient that was established after a 4 hour application
      of the patch and persisted over 24 hours. However, patches containing 3.5 mg of 5
      fluorouracil displayed signs of drug exhaustion after 24 hours. The penetration
      characteristics of 5-fluorouracil through cervical tissue using the cervical
      patch delivery system were sufficiently favourable to warrant further clinical
      investigations.

PMID- 7816763
TI  - Pulmonary deposition and clinical response of 99mTc-labelled salbutamol delivered
      from a novel multiple dose powder inhaler.
AB  - Pulmonary deposition of 99mTc-labelled sulbutamol was determined after delivery
      from a novel multiple dose powder inhaler (Easyhaler). The clinical efficacy of
      the inhalation powder, evaluated simultaneously with gamma camera detection, was
      compared with that obtained after drug delivery from a metered dose inhaler
      spacer combination. The study was performed as an open, non-randomized cross-over
      trial. A single dose of radiolabelled inhalation powder was inhaled on the first
      and the inhalation aerosol, as control, on the second study day. Sulbutamol
      sulphate was labelled with 99mtechnetium, and the inhalation powder was
      formulated by mixing radioactive drug particles with carrier material.
      Aerodynamic properties of the radiolabelled inhalation powder were similar to
      those of the unlabelled salbutamol powder. Delivered dose from the breath
      actuated powder inhaler was adjusted to be equal to two puffs from a conventional
      aerosol actuator with a short plastic mouthpiece. Twelve non-smoking asthmatic
      patients participated in the trial. The mean pulmonary deposition of 24% was
      obtained after drug delivery from Easyhaler powder inhaler. Clinical efficacy of
      the medications was similar in terms of area under the FEV1 curve, maximum FEV1
      and the improvement ratio. Thus it can be suggested that powder delivery from
      Easyhaler powder inhaler and the aerosol delivery through the spacer are equally
      effective.

PMID- 7816764
TI  - The determination of interfacial transfer constants using side-by-side diffusion
      cells.
AB  - A side-by-side diffusion cell setup has been used to determine the pH 7.4 buffer
      octanol interfacial transfer constants for twelve compounds. The compounds are a
      diverse selection of pharmaceuticals, amino acids, and small organics which
      covers a log distribution coefficient (K) range of -3 to 2. A model based on the
      resistance summation approach, which deals explicitly with the various barriers,
      involves in the transport process, was used to derive transfer constants from the
      transport data for each compound. The model gave constants that were well behaved
      in a published model describing the correlation of the forward and reverse
      transfer constants to equilibrium K values (r2 = 0.999). These studies
      demonstrate the utility of side-by-side diffusion cells for the determination of
      interfacial transfer constants. This type of setup offers the advantages of
      controlled interfacial area, measurable hydrodynamic effects, and a commercially
      available apparatus.

PMID- 7816765
TI  - Comparison of single and multiple dose pharmacokinetics using clinical
      bioequivalence data and Monte Carlo simulations.
AB  - The purpose of this study was to evaluate the relative performance and usefulness
      of single dose (SD) and multiple dose (MD) regimens for bioequivalence (BE)
      determination. Drugs such as indomethacin, procainamide, erythromycin, quinidine,
      nifedipine were tested for BE under SD and MD dose regimens. Drugs characterized
      by low accumulation indices (AI) showed virtually no change in the 90% confidence
      interval (CI) of AUC and CMAX upon multiple dosing. On the other hand, drugs with
      higher AI appeared to have smaller CI at steady-state. For example, the CI range
      of AUC and CMAX of quinidine (AI of 1.54) decreased from 26 to 12 and from 22 to
      12, respectively, upon multiple dosing. A Monte Carlo simulation study of SD and
      MD bioequivalence trials was performed. The probability of failing the
      bioequivalence test was evaluated for several situations defined by different
      levels of variability and correlation in ka constants, presence or absence of
      inter- and/or intra-individual variability in clearance (CL) and volume of
      distribution (V), and different degrees of accumulation. All the possible
      combinations of these factors were tested with SD and MD study designs. All
      simulations used 1000 data sets with 30 subjects in each data set for a total of
      144 unique designs (total of 144,000 simulations of bioequivalence trials). Upon
      multiple dosing, narrowing of CI ranges was observed for drugs simulated to have
      high AI high variability and a large difference in absorption constants (ka)
      between test and reference formulations.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7816766
TI  - Distribution kinetics of salicylic acid in the isolated perfused rat liver
      assessed using moment analysis and the two-compartment axial dispersion model.
AB  - The distribution kinetics of salicylic acid in the single-pass isolated perfused
      rat liver has been investigated under varying conditions of perfusate flow (15 to
      30 ml min-1) and of salicylate perfusate concentration (0, 100, 200 mg l-1) using
      statistical moment analysis and the two-compartment axial dispersion model.
      Salicylic acid was not metabolised during the experiment. The perfusate did not
      contain binding protein. As flow rate was increased, the maximum fraction output
      per second (f(t)max) increased and the mean transit time (MTTH) decreased, while
      tmax became shorter for both tritiated water and 14C-salicylic acid. Increasing
      the salicylate perfusate concentration profoundly affected the frequency outflow
      profile of 14C-salicylic acid, but not that of tritiated water. The one
      compartment axial dispersion model adequately described the frequency outflow
      profile for tritiated water, whereas the two-compartment form, which incorporates
      a cellular permeability barrier, provided a better description of the 14C
      salicylic acid outflow data. The estimated two-compartment axial dispersion model
      parameters for 14C-salicylic acid, DN, the dispersion number (0.08 +/- 0.03),
      k12, the influx rate constant (0.56 +/- 0.04 sec-1) and k21, the efflux rate
      constant (0.095 +/- 0.01 sec-1) were independent of perfusate flow rate. The in
      situ permeability-surface area product for 14C-salicylic acid (4.6 +/- 0.7 ml min
      1g-1 liver) was in good agreement with literature estimates obtained from in
      vitro hepatocyte experiments, suggesting that the permeability barrier is at the
      hepatocyte membrane. Whereas DN and k12 were uninfluenced by, k21 displayed a
      positive correlation with, salicylate perfusate concentration. This correlation
      was most likely due to decreased intracellular salicylate binding.

PMID- 7816767
TI  - Modeling of the saturable time-constrained amoxicillin absorption in humans.
AB  - Amoxicillin pharmacokinetics was modeled using a two-compartment disposition
      model and a saturable time-constrained absorption model with a storage
      compartment. The absorption model parameters estimated by the nonlinear
      regression are: a rate constant of the systemic input, ksys, (median: 1.31 h-1,
      range: 0.79-7.01 h-1), a maximal absorption rate, Vmax (median: 1407 mg/h, range:
      703-4181 mg/h), an account corresponding to the half maximal rate, Kma, (median:
      1077 mg, range: 235-4376 mg), time of the absorption cessation, Tabs, (median:
      1.72 h, range: 0.82-4.53 h) and absorption lag time. Tlag, (median: 0.085 h,
      range: 0-0.123 h). It was shown, that the first-order absorption parallel to the
      saturable process is negligible in the dose range studied. The model described
      well the dependence of areas under concentration-time curves on the dose
      determined in several earlier studies. It was used also to predict the fraction
      of the amoxicillin dose absorbed for different doses. Simulations performed over
      a wide dose range (50-10000 mg) demonstrated that the fraction absorbed decreases
      nonlinearly from 90% at 50 mg to 22% at 10000 mg and strongly depends on the
      duration of the absorption period.

PMID- 7816768
TI  - Peptide liquid crystals: inverse correlation of kinetic-formation and
      thermodynamic stability in aqueous solution.

PMID- 7816769
TI  - Impedance spectroscopy in human skin. A refined model.

PMID- 7816770
TI  - Effect of chitosan on the permeability of monolayers of intestinal epithelial
      cells (Caco-2).

PMID- 7816771
TI  - Characterization of the crystallinity of drugs: B02669, a case study.

PMID- 7816772
TI  - Leucine enkephalin effects on brain microvessel endothelial cell monolayer
      permeability.

PMID- 7816773
TI  - Adsorption of oligonucleotides onto polyisohexylcyanoacrylate nanoparticles
      protects them against nucleases and increases their cellular uptake.
AB  - Oligonucleotides can be adsorbed on polyisohexylcyanoacrylate nanoparticles in
      the presence of hydrophobic quarternary ammonium salts. Oligonucleotides bound to
      nanoparticles are protected from nuclease attack both in buffer and in cell
      culture media. Cellular uptake of oligonucleotides is increased when they are
      adsorbed onto nanoparticles as a result of the capture of nanoparticles by an
      endocytic phagocytic pathway. Intracellular stability towards nucleolytic
      degradation is increased in the presence of nanoparticles. These results show
      that nanoparticles can be considered as convenient carriers for the protection
      and delivery of oligonucleotides to cells.

PMID- 7816774
TI  - The present knowledge of the inflammatory process and the inflammatory mediators.
AB  - Endothelial damage, synovial oedema, fibrin deposition, polymorphonuclear cell
      (PMN) invasion, and mild lining cell hyperplasia characterize acute inflammatory
      arthritis. Later on, perivascular tissue is infiltrated by mononuclear cells. The
      early events are mediated by interactions between PMNs and endothelial cells.
      Both parts in the adhesion event are activated with multiple stimuli resulting in
      complex interactions of varying intensity and duration. Adhesion molecules
      present on the surface of PMNs (L-selectin) or induced by inflammatory stimuli
      (beta 2-integrins) mediate PMN adhesion to activated endothelium, which has
      counter receptors (E-selectin for L-selectin and ICAM-1 and ICAM-2 for beta 2
      integrins). At the initial phase L-selectin initiates the rolling of PMNs on
      endothelial cells. Further stimuli result in a more prolonged adhesion between
      PMNs and endothelium. At the side of endothelium, induction of P-selectin and PAF
      by histamine, thrombin and LTC4 contribute to the acute rolling of PMNs on
      endothelial surface. Tumor necrosis factor (TNF), interleukin-1 (IL-1) and
      lipopolysaccharide activate endothelial cells to synthesize interleukin-8 (IL-8),
      a potent chemotactic and proadhesive mediator for PMNs, and further adhesion
      molecule (E-selectin), a mediator of long-term adhesion between PMN and
      endothelium. After adhesion and migration to the focus of inflammation, PMNs
      induce inflammation by aggregating, releasing hydrolyzing enzymes, generating
      lipid peroxidation products such as prostaglandins and LTB4, and oxygen derived
      free radicals. In studies on the pathogenesis of seronegative
      spondyloarthropathies, we have shown persistently aberrant PMN function evidenced
      by enhanced chemotaxis and high production of toxic oxygen derived free radicals
      by PMN.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7816775
TI  - Pharmacology of tolfenamic acid.

PMID- 7816776
TI  - Biopharmaceutical aspects of tolfenamic acid.
AB  - The pharmacokinetics of tolfenamic acid is well described by a two-compartment
      model with relatively short half-lives (T/2 beta 1-2 hours) and tolfenamic acid
      is highly protein-bound with small volumes of distribution. It is cleared
      relatively fast (150-200 ml/min), mainly by hepatic metabolism and the
      metabolites are renally cleared as glucuronic acid conjugates. The peroral
      absorption is good and the peroral bioavailability is about 75%, as first pass
      metabolism accounts for about 20%. Tolfenamic acid shows linear pharmacokinetics
      and during multiple dosage regimen, i.e. thrice daily, no accumulation beyond the
      second dose is observed. The bioavailability in dependence of age and disease has
      been studied and only in the case of severe liver or kidney impairment, a change
      in dosage regimen seems warranted. The development of different formulations will
      be outlined, mainly on rectal delivery, on sustained release and rapid release
      oral formulations, on topical ointment, and on parenteral delivery. The problems
      with tolfenamic acid in pharmaceutical formulation caused mainly by poor
      solubility will be discussed. Formulations ready for the market now or very soon
      are Clotam capsules (tablets). Clotam retard tablets, Clotam suppositories, and
      Clotam oral suspension, whereas rapid tablets, topical ointments, and parenteral
      formulations need further development to be ready for marketing in the years to
      come.

PMID- 7816777
TI  - Influence of tolfenamic acid on airway contractility in guinea pigs.
AB  - The effect of the NSAIDs tolfenamic acid and indomethacin was tested on
      acetylcholine-induced and antigen-induced contractions in guinea pig airways.
      Indomethacin potentiated antigen-induced contractions while tolfenamic acid
      showed dilatory properties. The effects of the drugs on acetylcholine-induced
      contractions showed no significant differences; indomethacin had a slightly
      increasing tendency while tolfenamic acid reduced the contractile response. These
      results indicate that tolfenamic acid does not have bronchoconstrictive
      properties, which is a common side effect of other NSAIDs in asthmatics.

PMID- 7816778
TI  - Reported adverse drug reactions and consumption of non-steroidal anti
      inflammatory drugs.

PMID- 7816779
TI  - Prostanoids and leukotrienes in rheumatoid synovitis.

PMID- 7816780
TI  - Gastrointestinal tolerance studies on tolfenamic acid in humans and animals.

PMID- 7816781
TI  - A comparative study of the influence of tolfenamic acid (Clotam) and diclofenac
      sodium (Voltaren) on the gastrointestinal mucosa in patients with a history of
      NSAID-related dyspeptic symptoms.

PMID- 7816782
TI  - Relation of the use of analgesics and non-steroidal anti-inflammatory drugs
      (NSAIDs) to upper gastrointestinal bleeding: a preliminary report of a Finnish
      case-control prospective study.

PMID- 7816783
TI  - The overall safety of tolfenamic acid.

PMID- 7816784
TI  - Epidemiological and financial aspects of the use of non-steroidal anti
      inflammatory analgesics.
AB  - The availability of many new nonsteroidal anti-inflammatory drugs (NSAIDs) has
      increased the total consumption during the past 20 years. The cost of different
      NSAID brands varies considerably probably reflecting increased research and
      development costs rather than a true therapeutic benefit for the patient. The
      current therapeutic problem in the treatment of musculoskeletal conditions with
      NSAIDs is to make a balanced analysis between benefits, risks, and costs.
      Assessment of risks and benefits should focus on the large subgroup (about 40%)
      of elderly NSAID users over 60 years who clearly stand at increased risk of NSAID
      induced gastrointestinal complications. In the treatment of osteoarthritis more
      trials are needed to compare NSAIDs with plain analgesics (e.g. paracetamol).

PMID- 7816785
TI  - Tolfenamic acid and leukotriene synthesis inhibition.

PMID- 7816786
TI  - Tolfenamic acid: clinical experience in rheumatic diseases.
AB  - Tolfenamic acid (TA) is an interesting drug for the treatment of rheumatic
      diseases because of its capacity to inhibit the synthesis of leukotrienes. It may
      have fewer upper gastrointestinal side effects than other NSAIDs which inhibit
      only the synthesis of prostaglandins. Several controlled and non-controlled
      studies on the clinical efficacy and side effects of TA have been carried out
      since the early seventies. These studies include about 900 patients suffering
      from different rheumatic diseases. The clinical efficacy of TA has proved to be
      at least as good as that of control drugs in all double-blind trials. We have
      compared the analgesic effect of ten NSAIDs in patients with rheumatoid
      arthritis, using a single-blind method by asking the patients which one of two
      drugs was the better. The study gave a rank order to the drugs favoured by the
      patients and the results showed that TA was among the four best drugs together
      with naproxen, indomethacin, and diclofenac. The side effect profile of TA is
      different from that of other NSAIDs. The number of upper gastrointestinal side
      effects during TA treatment was less than half the number during treatment with
      control NSAIDs in eight double-blind studies. On the other hand, dysuria was
      found only during TA treatment. In 1989 the official side effect registers of
      Denmark and Finland included a total of 462 side effect reports. The frequency of
      side effects per treatment day was about the same as for other NSAIDs according
      to these reports.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7816787
TI  - Comparative studies with tolfenamic acid in rheumatic disorders.

PMID- 7816788
TI  - Migraine--diagnosis and pathophysiology.
AB  - The new classification of headaches will be briefly described. The main primary
      headaches are migraine with and without aura, tension-type headache and cluster
      headache. The operational diagnostic criteria for migraine with aura, migraine
      without aura and episodic tension-type headache will be presented. After this the
      clinical pictures of migraine with aura (previously classic migraine) and
      migraine without aura (previously common migraine) will be described. At last the
      current concepts concerning pathophysiology, regional cerebral blood flow
      changes, changes in extra- and intracranial arteries and mechanisms of action of
      ergotamine and sumatriptan will be presented.

PMID- 7816789
TI  - Tolfenamic acid and migraine--aspects on prostaglandins and leukotrienes.
AB  - Migraine is a paroxysmal disorder characterized by recurrent attacks of headache,
      with or without associated visual and gastrointestinal disturbances. Migraine can
      be classified in two main groups, common and classic. Theories trying to explain
      the pathogenesis of a migraine attack may emphasize either the central or
      peripheral aspects of the disease. The vascular theory may stress the importance
      of either central or peripheral blood flow or both. Cerebral vasoconstriction in
      the early phases of the attack is followed by vasodilatation and pain.
      Biochemical mediators of vascular responses are not exactly known, but platelets
      and 5-hydroxytryptamine and thromboxane released from them as well as
      noradrenaline are potent vasoconstrictors, while kinins and prostaglandins can
      explain the vasodilatory phase of migraine attacks. This review presents evidence
      for the role of arachidonic acid metabolites, prostaglandins and leukotrienes in
      migraine. The evidence comes from the measurements of eicosanoids in biological
      fluids during and after the attack, infusion studies where vasodilatory
      prostaglandins mimic the migraneous symptoms, and the good effect of non
      steroidal anti-inflammatory drugs in the treatment and prophylaxis of migraine
      attacks. Additional data are based on experimental biochemical studies in which
      catecholamines and indolamines have been shown to increase the synthesis of
      vasodilatory prostaglandins. However, the final evidence still awaits its
      confirmation.

PMID- 7816790
TI  - Tolfenamic acid in acute and prophylactic treatment of migraine: a review.
AB  - The possible role of prostaglandins (PGs) in migraine has been the subject of
      increasing attention after the rather dramatic experiments done in man by
      Bergstrom and coworkers more than 25 years ago (1965). The role of PGs in
      migraine, however, is still hypothetical and not yet explained. PGs are known to
      sensitize nociceptors and produce hyperalgesia. PGs are involved in platelet
      aggregation thereby releasing serotonin. Vasodilatation, oedema and hyperalgesia
      in migraine have much in common with an inflammatory reaction. Tolfenamic acid
      (TA) inhibits PG biosynthesis and action and has an anti-aggregatory effect. TA
      is better than aspirin and as effective as ergotamine in treatment of acute
      migraine attacks. TA has fewer side effects than ergotamine. TA is as effective
      as propranolol in prophylactic treatment of migraine. The dose regimen of TA in
      acute treatment of migraine is 200 mg when the first symptoms of migraine appear.
      The treatment can be repeated after 2-3 hours if satisfactory effect is not
      obtained. The dose regimen of TA in prophylactic treatment of migraine is one
      sustained release tablet of 300 mg or 100 mg 3 times daily. After a treatment
      period of three months the regimen should be re-evaluated.

PMID- 7816791
TI  - The use of arachidonic acid in some gynaecological disorders.

PMID- 7816792
TI  - Prostaglandin synthesis inhibitors in menorrhagia, intrauterine contraceptive
      device-induced side effects and endometriosis.
AB  - Primary menorrhagia, IUD side effects and endometriotic symptoms may be a result
      of excessive PG release in the reproductive organs. These conditions and symptoms
      can be prevented or markedly alleviated by a PG synthesis inhibitor, such as
      tolfenamic acid. This treatment, which is used only intermittently, has been well
      tolerated with no serious side effects.

PMID- 7816793
TI  - Tolfenamic acid and mefenamic acid in the treatment of primary dysmenorrhoea.
AB  - The clinical efficacy of tolfenamic acid and mefenamic acid in the treatment of
      primary dysmenorrhoea was studied in a prospective, controlled, double-blind,
      cross-over study comprising 73 patients aged 13-39 with an average body weight of
      56 kilos. The patients were randomized to receive either tolfenamic acid (200 mg
      t.i.d.) or mefenamic acid (500 mg t.i.d.) for 3 days, during 3 consecutive
      menstrual cycles each, in a sequential design A-B or B-A. At the beginning and at
      the end of each treatment period, 13 dysmenorrhoeic symptoms were evaluated on a
      visual analogue scale (lower back pain, interference with daily activities,
      nausea, vomiting, diarrhoea, headache, dizziness, fatigue, sweating, chills, hot
      flashes, depressant states, and mood swings). The data were analyzed by using two
      statistical models. The first one, for the 73 patients, by making paired
      comparisons regardless of treatment sequence. With respect to the initial values,
      the results showed that both drugs were statistically significant (P < 0.05) in
      reducing the intensity of the evaluated symptoms. When comparing both treatments,
      tolfenamic acid showed a significant difference as to interference with daily
      activities (P < 0.025) and hot flashes (P < 0.005). In the result analysis with
      the second model, the groups were divided according to the first assigned
      treatment and paired comparisons were made. It was observed that the group
      receiving tolfenamic acid in the last sequence reached a higher level of response
      and statistical significance was demonstrated in 8 of 13 evaluated
      symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7816794
TI  - Inhibition of eicosanoid synthesis and potential therapeutic benefits of 'dual
      pathway inhibition'.

PMID- 7816795
TI  - Chemical ecology.

PMID- 7816797
TI  - Sequential induction of 5-lipoxygenase gene expression and activity in Mono Mac 6
      cells by transforming growth factor beta and 1,25-dihydroxyvitamin D3.
AB  - 5-Lipoxygenase (5-LO; EC 1.13.11.34) activity in the human monocytic cell line
      Mono Mac 6 was upregulated by combined treatment with transforming growth factor
      beta 1 (TGF-beta) and 1,25-dihydroxyvitamin D3 (VD3). In undifferentiated cells,
      5-LO enzyme activity was undetectable. After the addition of TGF-beta plus VD3,
      the activity of intact cells was 800 ng per 10(6) cells--500 times more than the
      assay detection limit. Also 5-LO protein and mRNA expression were induced > 128
      fold and 64-fold, respectively, as compared to undifferentiated cells. Both TGF
      beta and VD3 were required for these prominent responses. Either agent alone gave
      small amounts of 5-LO protein and mRNA but very low 5-LO activities. After the
      addition of TGF-beta and VD3, the induction of 5-LO protein was obvious after 1
      day, but the increase in activity was delayed and did not appear until the second
      day. Pretreatment of cells with TGF-beta or VD3 alone for 2 days led to 5-LO
      protein expression but very low enzyme activity. Addition of the lacking second
      inducer was required for full induction of 5-LO protein expression and for
      upregulation of enzyme activity. Partial purification of 5-LO from Mono Mac 6
      cells and recombination with soluble cellular proteins from different sources
      indicated the presence of cytosolic factors that affect the activity of 5-LO.

PMID- 7816796
TI  - Different topoisomerase II antitumor drugs direct similar specific long-range
      fragmentation of an amplified c-MYC gene locus in living cells and in high-salt
      extracted nuclei.
AB  - We have analyzed the long-range distribution of topoisomerase II-mediated
      cleavages induced in an amplified human c-MYC gene locus in the presence of
      several antitumor agents. The long-range cleavage patterns were found to be
      nonrandom and similar for all antitumor drugs tested. Cleavages occurred within
      several kilobase-long areas (approximately 5 kb) highly accessible to
      topoisomerase II and separated by extended regions (approximately 70-100 kb) of
      less accessibility, possibly reflecting the mode of DNA organization into loops
      along the chromosome. Within the cleavage areas, the patterns of cleavage sites
      showed a certain dependence on the type of drug used for entrapment of
      topoisomerase II-DNA complexes. Importantly, distribution of cleavage areas in
      native chromatin and histone-depleted nuclei was very similar, if not identical,
      suggesting that the primary target of antitumor agents in vivo is topoisomerase
      II associated with the high-salt-insoluble nuclear matrix. These data show that
      matrix-attached DNA is preferentially damaged by topoisomerase II-targeting
      agents, which may be an important cellular event contributing to drug-induced
      cell death.

PMID- 7816798
TI  - The Saccharomyces cerevisiae phosphatidylinositol-transfer protein effects a
      ligand-dependent inhibition of choline-phosphate cytidylyltransferase activity.
AB  - The Saccharomyces cerevisiae protein SEC14p is required for Golgi function and
      cell viability in vivo. This requirement is obviated by mutations that
      specifically inactivate the CDP-choline pathway for phosphatidylcholine
      biosynthesis. The biochemical basis for the in vivo relationship between SEC14p
      function and the CDP-choline pathway has remained obscure. We now report that
      SEC14p effects an in vivo depression of CDP-choline pathway activity by
      inhibiting choline-phosphate cytidylyltransferase (CCTase; EC 2.7.7.15), the rate
      determining enzyme of the CDP-choline pathway. Moreover, this SEC14p-mediated
      inhibition of CCTase was recapitulated in vitro and was saturable. Finally,
      whereas the SEC14p-dependent inhibition of CCTase in vitro was markedly reduced
      under assay conditions that were expected to increase levels of
      phosphatidylinositol-bound SEC14p, assay conditions expected to increase levels
      of phosphatidylcholine-bound SEC14p resulted in significant potentiation of
      CCTase inhibition. The collective data suggest that the phosphatidylcholine-bound
      form of SEC14p effects an essential repression of CDP-choline pathway activity in
      Golgi membranes by inhibiting CCTase and that the phospholipid-binding/exchange
      activity of SEC14p represents a mechanism by which the regulatory activity of
      SEC14p is itself controlled.

PMID- 7816799
TI  - "Latent" inhibitory connections become functional during activity-dependent
      plasticity.
AB  - Simultaneous pre- and postsynaptic recordings from identified glycinergic
      inhibitory interneurons and the Mauthner cell showed that 25% of the afferents
      produced no or extremely small postsynaptic responses. Morphological
      determination of the number of contacts made by these cells on the Mauthner cell
      revealed a connectivity similar to that of functional neurons which always
      produce clear inhibitory postsynaptic potentials, suggesting that most of the
      endings, made by weak interneurons are silent. Intraaxonal injection of 4
      aminopyridine or Ca2+ greatly enhanced transmission at functional connections but
      did not modify those which were ineffective. However, after eighth nerve tetanic
      stimuli, transmission at the weak connections was unmasked or enhanced for
      prolonged periods and was twice as likely to be potentiated, with a 6-fold
      greater mean enhancement than the potent ones. This result provides additional
      support for long-term potentiation of inhibitory synapses. Furthermore, weakly
      functional junctions represent a "reserve" pool which can be critical for the
      expression of plasticity within a network, and, consequently, for setting the
      threshold of reflex activities such as the escape reaction mediated by the
      Mauthner cell.

PMID- 7816800
TI  - Functional coupling of Ca2+ channels and ryanodine receptors in cardiac myocytes.
AB  - In skeletal muscle, dihydropyridine receptors are functionally coupled to
      ryanodine receptors of the sarcoplasmic reticulum in triadic or diadic junctional
      complexes. In cardiac muscle direct physical or functional couplings have not
      been demonstrated. We have tested the hypothesis of functional coupling of L-type
      Ca2+ channels and ryanodine receptors in rat cardiac myocytes by comparing the
      efficacies of Ca2+ in triggering Ca2+ release when the ion enters the cell via
      the Ca2+ channels or the Na+/Ca2+ exchanger. Ca2+ transported through the Ca2+
      channels was 20-160 times more effective than Ca2+ influx via the Na+/Ca2+
      exchanger in gating Ca2+ release from the sarcoplasmic reticulum, suggesting
      privileged communication between Ca2+ channels and ryanodine receptors. In
      support of this hypothesis we found that Ca2+ channels were inactivated by Ca2+
      release from the sarcoplasmic reticulum, even though the myoplasmic Ca2+
      concentrations were buffered with 10 mM EGTA. The data thus suggest privileged
      cross signaling between the dihydropyridine and ryanodine receptors such that
      Ca2+ flux through either the Ca2+ channel or the ryanodine receptor alters the
      gating kinetics of the other channel.

PMID- 7816801
TI  - Expression of an active glycosylated human gamma-glutamyl transpeptidase mutant
      that lacks a membrane anchor domain.
AB  - A mutant of human gamma-glutamyl transpeptidase (EC 2.3.2.2, a membrane-bound
      enzyme of importance in glutathione metabolism) that differs from the wild type
      by deletion of the putative signal peptide/anchor domain (amino acid residues 1
      27) was expressed in insect cells using a baculovirus system. In contrast to the
      wild-type enzyme--which, as expected, was mainly cell-associated--the mutant
      enzyme was secreted into the medium. The mutant and wild-type enzymes were
      purified and found to exhibit virtually identical catalytic properties. The
      mutant enzyme was glycosylated and processed into two subunits, as found for the
      wild-type enzyme. Brefeldin A inhibited secretion of the mutant enzyme and led to
      its accumulation in cells. The findings indicate that gamma-glutamyl
      transpeptidase can be targeted to the endoplasmic reticulum in a manner that does
      not involve function of an amino-terminal "signal/anchor" domain and that this
      domain is involved primarily in a membrane anchoring function. Another region of
      the enzyme may function as a signal domain.

PMID- 7816803
TI  - Expression of the wild-type p53 antioncogene induces guanine nucleotide-dependent
      stem cell division kinetics.
AB  - The predominant type of cell division in adult mammals is renewal growth.
      Renewing stem cells in somatic tissues undergo continuous asymmetric divisions.
      One new daughter cell retains the division potential of the original stem cell,
      while the other differentiates into a functional constituent of the tissue.
      Disruptions of this process lead to the development of human cancers. We show
      that through a guanine nucleotide-dependent mechanism, the p53 antioncogene can
      induce exponentially dividing cells to switch to an asymmetric stem cell growth
      pattern. This finding suggests that the observed high frequency of p53 mutations
      in human cancers reflects a critical function in the regulation of somatic
      renewal growth.

PMID- 7816802
TI  - Cloning and functional expression of a rat kidney extracellular
      calcium/polyvalent cation-sensing receptor.
AB  - The maintenance of a stable extracellular concentration of ionized calcium
      depends on the integrated function of a number of specialized cells (e.g.,
      parathyroid and certain kidney epithelial cells). We recently identified another
      G protein-coupled receptor (BoPCaRI) from bovine parathyroid that responds to
      changes in extracellular Ca2+ within the millimolar range and provides a key
      mechanism for regulating the secretion of parathyroid hormone. Using an homology
      based strategy, we now report the isolation of a cDNA encoding an extracellular
      Ca2+/polyvalent cation-sensing receptor (RaKCaR) from rat kidney. The predicted
      RaKCaR protein shares 92% identity with BoPCaR1 receptor and features a seven
      membrane-spanning domain, characteristic of the G protein-coupled receptors,
      which is preceded by a large hydrophilic extracellular NH2 terminus believed to
      be involved in cation binding. RaKCaR cRNA-injected Xenopus oocytes responded to
      extracellular Ca2+, Mg2+, Gd3+, and neomycin with characteristic activation of
      inositol phospholipid-dependent, intracellular Ca(2+)-induced Cl- currents. In
      rat kidney, Northern analysis revealed RaKCaR transcripts of 4 and 7 kb, and in
      situ hybridization showed localization primarily in outer medulla and cortical
      medullary rays. Our results provide important insights into the molecular
      structure of an extracellular Ca2+/polyvalent cation-sensing receptor in rat
      kidney and provide another basis on which to understand the role of extracellular
      divalent cations in regulating kidney function in mineral metabolism.

PMID- 7816805
TI  - Origin of the foraminifera.
AB  - We report nuclear small-subunit rDNA sequences for two species of the benthic
      foraminifer Ammonia. Because of their abundance in present and past seas, the
      foraminifera are a very important group of organisms used in a wide range of
      geologic studies; however, the ancestry of this group was, until now, unknown.
      Difficulties in purifying foraminiferal DNA and avoiding PCR contamination led us
      to develop DNA.DNA in situ hybridization techniques to verify our sequence data.
      Phylogenetic analysis of verified foraminiferal DNA sequence indicates these taxa
      are a divergent, "alveolate" lineage, within the major eukaryotic radiation. Our
      findings cast doubt upon the assumption that all foraminifera are derived from an
      amoebalike ancestor. Cytological features and the DNA sequences presented herein
      suggest that the foraminifera were derived from a heterokaryotic flagellated
      marine protist, probably sometime in the later Proterozoic.

PMID- 7816804
TI  - The chemistry of phyletic dominance.
AB  - Studies of arthropod defensive chemistry continue to bring to light novel
      structures and unanticipated biosynthetic capabilities. Insect alkaloids, such as
      the heptacyclic acetogenin chilocorine and the azamacrolides, exemplify both of
      these aspects of arthropod chemistry. Spider venoms are proving to be rich
      sources of neuroactive components of potential medical interest. The venom of a
      fishing spider, Dolomedes okefinokensis, has yielded a polyamine which reversibly
      blocks L- and R-type voltage-sensitive calcium channels. Most recently, we have
      characterized, from the funnel-web spider Hololena curta, a sulfated nucleoside
      glycoside which serves as a reversible blocker of glutamate-sensitive calcium
      channels. The ability to synthesize or acquire an extremely diverse array of
      compounds for defense, offense, and communication appears to have contributed
      significantly to the dominant position that insects and other arthropods have
      attained.

PMID- 7816806
TI  - Forces of tertiary structural organization in globular proteins.
AB  - The tertiary structures of globular proteins have remarkable and complex
      symmetries. What forces cause them? We find that a very simple model reproduces
      some of those symmetries. Proteins are modeled as copolymers of specific
      sequences of hydrophobic (H) and polar (P) monomers (HP model) configured as self
      avoiding flights on simple three-dimensional cubic lattices. The model has no
      parameters; we just seek the conformations that have the global maximum number of
      HH contacts for any given sequence. Finding global optima for chains in this
      model has not been computationally possible before for chains longer than 36
      mers. We report here a procedure that can find all the globally optimal
      conformations, the number of which defines the degeneracy of a sequence, for
      chains up to 88 monomers long. It is about 37 orders of magnitude faster than
      previous exact methods. We find that degeneracy is an important aspect of
      sequence design. So far, we have found that four-helix bundles, alpha/beta
      barrels, and parallel beta-helices are globally optimal conformations of
      polar/nonpolar sequences that have minimal degeneracy.

PMID- 7816807
TI  - Comparative genomic analysis of tumors: detection of DNA losses and
      amplification.
AB  - We demonstrate the use of representational difference analysis for cloning probes
      that detect DNA loss and amplification in tumors. Using DNA isolated from human
      tumor cell lines to drive hybridization against matched normal DNA, we were able
      to identify six genomic regions that are homozygously deleted in cultured cancer
      cells. When this method was applied in the reverse way, using normal DNA to drive
      hybridization against tumor cell DNA, we readily isolated probes detecting
      amplification. Representational difference analysis was also performed on DNAs
      derived from tumor biopsies, and we thereby discovered a probe detecting very
      frequent homozygous loss in colon cancer cell lines and located on chromosome 3p.

PMID- 7816809
TI  - Site-specific recombination of a transgene in fertilized eggs by transient
      expression of Cre recombinase.
AB  - An efficient method of transgene modulation in fertilized eggs has been developed
      that uses the Cre/loxP recombination system. Twelve transgenic mouse lines
      carrying a chicken beta-actin promoter-loxP-chloramphenicol acetyltransferase
      (CAT) gene-loxP-beta-galactosidase gene construct were produced. After selection
      of the line showing the highest expression of the CAT gene in a variety of
      tissues, eggs of this line were injected in the male or female pronucleus with a
      Cre expression vector placed under the control of the chicken beta-actin promoter
      and kept in a circular form to avoid genomic integration. This resulted in a
      transient expression of Cre in the eggs, leading to recombination of the
      transgene as detected by galactosidase expression and DNA analysis. Recombination
      was completed before the morula stage with both types of pronuclear injections
      and occurred with a very high frequency; no mosaicism, no incomplete
      recombination, and no integration of the Cre sequence were observed in 18 mice
      born with this modified transgene. The beta-galactosidase gene was expressed in
      various tissues at levels comparable to those found for the CAT gene in the
      founder line. This Cre transient expression system should be useful for breeding
      transgenic lines in which transgene expression leads to sterility or lethality-
      in particular, for selecting transgenic lines with high expression of a
      potentially lethal transgene whose full activity is difficult to explore in a
      conventional transgenic system because of the risk of selecting for transgenic
      lines carrying only poorly expressed transgenes.

PMID- 7816808
TI  - Steroid/thyroid hormone receptor genes in Caenorhabditis elegans.
AB  - The large family of steroid/thyroid hormone receptor (STR) genes has been
      extensively studied in vertebrates and insects but little information is
      available on it in more primitive organisms. All members possess a DNA binding
      domain of zinc fingers of the C2, C2 type. We have used the polymerase chain
      reaction with degenerate oligonucleotide primers covering this region to clone
      three distinct members of this family from the nematode Caenorhabditis elegans.
      All three belong to the retinoic acid receptor (RAR), thyroid hormone receptor
      subfamily of genes. The cDNA of one of these clones shows such a high homology to
      DHR3, an early ecdysone response gene found in Drosophila, and MHR3, identified
      in Manduca sexta, that we have termed it CHR3. Furthermore, the C-terminal
      portion of the deduced protein sequence shows a box containing eight identical
      amino acids among CHR3, DHR3, and MHR3 suggesting an identical specific ligand
      for these proteins. CNR8 shows homology to NAK1, and CNR14 has homology to both
      the RAR-gamma 1 gene and to another ecdysone response gene, E78A. Neither of the
      latter two cDNAs is a clear homologue of any known gene and each is distinctive.
      All of these genes are expressed varyingly in both larval and adult stages of
      nematode development as shown by Northern blot analyses. These data demonstrate
      that the STR family of genes is represented in a nematode whose ancestor appeared
      well before the branching that gave rise to the Arthropoda and Chordata.

PMID- 7816810
TI  - Optical mapping of site-directed cleavages on single DNA molecules by the RecA
      assisted restriction endonuclease technique.
AB  - Fluorescence in situ hybridization (FISH) resolution has advanced because newer
      techniques use increasingly decondensed chromatin. FISH cannot analyze
      restriction enzyme cutting sites due to limitations of the hybridization and
      detection technologies. The RecA-assisted restriction endonuclease (RARE)
      technique cleaves chromosomal DNA at a single EcoRI site within a given gene or
      selected sequence. We recently described a mapping technique, optical mapping,
      which uses fluorescence microscopy to produce high-resolution restriction maps
      rapidly by directly imaging restriction digestion cleavage events occurring on
      single deproteinized DNA molecules. Ordered maps are then constructed by noting
      fragment order and size, using several optically based techniques. Since we also
      wanted to map arbitrary sequences and gene locations, we combined RARE with
      optical mapping to produce site-specific visible EcoRI restriction cleavage sites
      on single DNA molecules. Here we describe this combined method, named optical
      RARE, and its initial application to mapping gene locations on yeast chromosomes.

PMID- 7816811
TI  - Supramolecular structure of the photosystem II complex from green plants and
      cyanobacteria.
AB  - Photosystem II (PSII) complexes, isolated from spinach and the thermophilic
      cyanobacterium Synechococcus elongatus, were characterized by electron microscopy
      and single-particle image-averaging analyses. Oxygen-evolving core complexes from
      spinach and Synechococcus having molecular masses of about 450 kDa and dimensions
      of approximately 17.2 x 9.7 nm showed twofold symmetry indicative of a dimeric
      organization. Confirmation of this came from image analysis of oxygen-evolving
      monomeric cores of PSII isolated from spinach and Synechococcus having a mass of
      approximately 240 kDa. Washing with Tris at pH 8.0 and analysis of side-view
      projections indicated the possible position of the 33-kDa extrinsic manganese
      stabilizing protein. A larger complex was isolated that contained the light
      harvesting complex II (LHC-II) and other chlorophyll a/b-binding proteins, CP29,
      CP26, and CP24. This LHC-II-PSII complex had a mass of about 700 kDa, and
      electron microscopy revealed it also to be a dimer having dimensions of about
      26.8 and 12.3 nm. From comparison with the dimeric core complex, it was deduced
      that the latter is located in the center of the larger particle, with additional
      peripheral regions accommodating the chlorophyll a/b-binding proteins. It is
      suggested that two LHC-II trimers are present in each dimeric LHC-II-PSII complex
      and that each trimer is linked to the reaction center core complex by CP24, CP26,
      and CP29. The results also suggest that PSII may exist as a dimer in vivo.

PMID- 7816812
TI  - Stereoelectronic effects of deoxyribose O4' on DNA conformation.
AB  - While B-DNA, the most common DNA conformation, displays rather regular twist
      angles and base stacking between successive base pairs, left-handed Z-DNA is
      characterized by the alternation of two different dinucleotide conformations with
      either a large twist and a small slide or a small twist and a large slide between
      adjacent base pairs. This results in poor stacking within the latter dinucleotide
      repeat that is in apparent contradiction to the rigidity and conformational
      stability of Z-DNA at high ionic strength. However, at d(CpG) steps the cytidine
      deoxyribose is situated such that its O4' sits directly over the six-membered
      ring of the guanine. We show here that the particular positionings of the two O4'
      lone-pair electrons provide stability through an intracytidine O4'...H6--C6
      hydrogen bond and an n-->pi* interaction with the guanidinium system of the
      stacked base. Our model is based on the assumption of a strong polarization of
      the guanine bases in Z-DNA that is consistent with the Z-DNA-specific guanine O6
      and N7 coordination to metal and organic cations and the proximity of its N2 and
      C8 positions to neighboring phosphate groups, as well as several other Z-DNA
      specific conformational features.

PMID- 7816814
TI  - The chemistry of social regulation: multicomponent signals in ant societies.
AB  - Chemical signals mediating communication in ant societies are usually complex
      mixtures of substances with considerable variation in molecular composition and
      in relative proportions of components. Such multicomponent signals can be
      produced in single exocrine glands, but they can also be composed with secretions
      from several glands. This variation is often functional, identifying groups or
      specific actions on a variety of organizational levels. Chemical signals can be
      further combined with cues from other sensory modalities, such as vibrational or
      tactile stimuli. These kinds of accessory signals usually serve in modulatory
      communication, lowering the response threshold in the recipient for the actual
      releasing stimulus. Comparative studies suggest that modulatory signals evolved
      through ritualization from actions originally not related to the same behavioral
      context, and modulatory signals may further evolve to become independent
      releasing signals.

PMID- 7816813
TI  - Urea unfolding of peptide helices as a model for interpreting protein unfolding.
AB  - To provide a model system for understanding how the unfolding of protein alpha
      helices by urea contributes to protein denaturation, urea unfolding was measured
      for a homologous series of helical peptides with the repeating sequence Ala-Glu
      Ala-Ala-Lys-Ala and chain lengths varying from 14 to 50 residues. The dependence
      of the helix propagation parameter of the Zimm-Bragg model for helix-coil
      transition theory (s) on urea molarity ([urea]) was determined at 0 degree C with
      data for the entire set of peptides, and a linear dependence of In s on [urea]
      was found. The results were fitted by the binding-site model and by the solvent
      exchange model for the interaction of urea with the peptides. Each of these
      thermodynamic models is able to describe the data quite well and we are not able
      to discern any difference between the ability of each model to fit the data. Thus
      a linear relation, ln s = ln s0 - (m/RT).[urea], fits the data for alpha-helix
      unfolding, just as others have found for protein unfolding. When the m value
      determined here for alpha-helix unfolding is multiplied by the number of helical
      residues in partly helical protein molecules, the resulting values agree within a
      factor of 2 with observed m values for these proteins. This result indicates that
      the interaction between urea and peptide groups accounts for a major part of the
      denaturing action of urea on proteins, as predicted earlier by some model studies
      with small molecules.

PMID- 7816815
TI  - Increased cell surface expression and enhanced folding in the endoplasmic
      reticulum of a mutant erythropoietin receptor.
AB  - In both transfected and normal hematopoietic cells, the majority of newly made
      erythropoietin receptor (EPO-R) subunits are retained in the endoplasmic
      reticulum (ER), destined for degradation. Only a small fraction exit the ER and
      are competent to bind EPO, suggesting that the EPO-R folds inefficiently. The EPO
      R contains a 5-amino acid motif, WSXWS, in the extracellular domain that is
      conserved among members of the cytokine receptor family. We describe a mutant EPO
      R with a change in the middle residue of this motif, A234E, that is transported
      from the ER more efficiently than the wild-type (wt) receptor and is expressed in
      elevated numbers at the cell surface. This mutant polypeptide is processed more
      efficiently in the ER than its wt counterpart, suggesting that it folds better
      than the wt EPO-R. Inefficient folding and processing of the wt EPO-R in the ER
      may be one mechanism for controlling the number of plasma membrane receptors.

PMID- 7816816
TI  - The chemistry of defense: theory and practice.
AB  - Defensive chemicals used by organisms for protection against potential consumers
      are generally products of secondary metabolism. Such chemicals are characteristic
      of free-living organisms with a limited range of movement or limited control over
      their movements. Despite the fact that chemical defense is widespread among
      animals as well as plants, the vast majority of theories advanced to account for
      patterns of allocation of energy and materials to defensive chemistry derive
      exclusively from studies of plant-herbivore interactions. Many such theories
      place an undue emphasis on primary physiological processes that are unique to
      plants (e.g., photosynthesis), rendering such theories limited in their utility
      or predictive power. The general failure of any single all-encompassing theory to
      gain acceptance to date may indicate that such a theory might not be a
      biologically realistic expectation. In lieu of refining theory, focusing
      attention on the genetic and biochemical mechanisms that underlie chemical
      defense allocation is likely to provide greater insights into understanding
      patterns across taxa. In particular, generalizations derived from understanding
      such mechanisms in natural systems have immediate applications in altering
      patterns of human use of natural and synthetic chemicals for pest control.

PMID- 7816817
TI  - Structure, characterization, and expression of the rat oxytocin receptor gene.
AB  - The multiple hormonal and neurotransmitter functions of the nonapeptide oxytocin
      are mediated by specific oxytocin receptors (OTRs). In most target tissues, the
      number of OTRs is strongly regulated. Specifically, in the uterus, a dramatic OTR
      upregulation precedes the onset of parturition. To study the molecular mechanisms
      underlying OTR regulation, we have isolated and characterized recombinant
      bacteriophage lambda EMBL3 genomic clones containing the rat OTR gene, using
      sequence information derived from a human myometrial OTR cDNA. The rat OTR gene
      spans > 20 kb and contains three exons. A 97-bp intron is in the 5' untranslated
      region and a > 12-kb intron interrupts the coding region between transmembrane
      domains 6 and 7. The promoter region lacks an apparent TATA or CCAAT box but
      contains multiple putative interleukin-response elements [six NF-IL6 (C/EBP beta)
      and four APRF (STAT3) binding motifs], supporting the notion that interleukins
      may mediate labor induction via transcriptional activation of the OTR gene. The
      predicted amino acid sequence is 93% identical to the human OTR sequence but only
      48% and 38% identical to the rat V1 and V2 vasopressin receptor sequences,
      respectively. At parturition, the OTR gene is highly expressed in the rat uterus
      and gives rise to at least three transcripts (2.9, 4.8, and 6.7 kb) which differ
      in the length of their 3' untranslated regions.

PMID- 7816818
TI  - Overexpression of plasminogen activator inhibitor 2 in human melanoma cells
      inhibits spontaneous metastasis in scid/scid mice.
AB  - A metastatic human melanoma cell line that produces urokinase-type plasminogen
      activator was stably transfected with cDNA encoding human plasminogen activator
      inhibitor 2 (PAI-2). Transfected clones expressed PAI-2 at levels two to nine
      times higher than both the parental cell line and mock transfectants, as detected
      by ELISA of cell lysates and conditioned medium. The clone with the highest PAI-2
      expression exhibited complete inhibition of soluble and cell-surface-bound
      plasminogen activator activity. The level of PAI-2 overexpression in these clonal
      cell lines correlated positively with the inhibition of their ability to degrade
      extracellular matrix in vitro. Parental, mock-transfected, and PAI-2-transfected
      cell lines produced rapidly growing tumors when injected s.c. into the skin of
      mice with severe combined immunodeficiency. The tumors producing the highest
      levels of PAI-2 were surrounded by a dense tumor capsule. Both parental cells and
      mock-transfected cells invariably metastasized from s.c. tumors to lymph nodes
      and lungs of mice. PAI-2-transfected cell lines produced significantly less or no
      metastases. Taken together, these data indicate a critical role for plasminogen
      activator activity in melanoma invasion and metastasis.

PMID- 7816819
TI  - Brain-derived neurotrophic factor promotes the survival of neurons arising from
      the adult rat forebrain subependymal zone.
AB  - Neuronal precursor cells persist in the adult forebrain ependymal/subependymal
      zone (SZ) and have been found to produce neurons in cultures derived from birds,
      rodents, and humans. We postulated that the survival of neurons generated from
      these cells might be constrained in adulthood by the local absence of trophic
      support. To test this hypothesis, we established explant cultures of adult rat
      forebrain SZ and assessed the effect of defined neurotrophins on the survival of
      new neurons arising from these explants. We found that microtubule-associated
      protein 2+ neurons arose from explants derived from a wide area of the SZ,
      spanning the rostral 6 mm of the ventricular system. In cultures exposed to brain
      derived neurotrophic factor (BDNF), > 35% of new neurons survived at 22 days in
      vitro (DIV), and > 25% survived at 42 DIV, concurrent with the virtually complete
      loss of neurons in unsupplemented controls. The surviving cells expressed trkB,
      the high-affinity receptor for BDNF. In contrast, neither nerve growth factor nor
      neurotrophic factor 3 enhanced neuronal survival. Thus, BDNF supports the
      survival of neurons produced by the adult rat forebrain and may act as a
      permissive factor for neuronal recruitment in adulthood.

PMID- 7816821
TI  - Altered behavior and long-term potentiation in type I adenylyl cyclase mutant
      mice.
AB  - The murine Ca(2+)-stimulated adenylyl cyclase (type I) (EC 4.6.1.1), which is
      expressed predominantly in brain, was inactivated by targeted mutagenesis. Ca(2+)
      stimulated adenylyl cyclase activity was reduced 40-60% in the hippocampus,
      neocortex, and cerebellum. Long-term potentiation in the CA1 region of the
      hippocampus from mutants was perturbed relative to controls. Both the initial
      slope and maximum extent of changes in synaptic response were reduced. Although
      mutant mice learned to find a hidden platform in the Morris water task normally,
      they did not display a preference for the region where the platform had been when
      it was removed. These results indicate that disruption of the gene for the type I
      adenylyl cyclase produces changes in behavior and that the cAMP signal
      transduction pathway may play an important role in synaptic plasticity.

PMID- 7816820
TI  - Anti-human immunodeficiency virus 1 (HIV-1) activities of 3-deazaadenosine
      analogs: increased potency against 3'-azido-3'-deoxythymidine-resistant HIV-1
      strains.
AB  - 3-Deazaadenosine (DZA), 3-deaza-(+/-)-aristeromycin (DZAri), and 3
      deazaneplanocin A (DZNep) are powerful modulators of cellular processes. When
      tested against H9 cells infected acutely with two different strains of human
      immunodeficiency virus 1 (HIV-1) and in the chronically infected monocytoid cell
      lines U1 and THP-1, the 3-deazanucleosides caused a marked reduction in p24
      antigen production. Similar reductions in p24 antigen were seen in
      phytohemagglutinin-stimulated peripheral blood mononuclear cells infected with
      clinical HIV-1 isolates. Strikingly, in comparing the therapeutic indices between
      the paired pre- and post-3'-azido-3'-deoxythymidine (AZT) treatment HIV-1
      isolates, DZNep and neplanocin A showed an increase of 3- to 18-fold in their
      potency against AZT-resistant HIV-1 isolates. In H9 cells treated with DZNep and
      DZAri, the formation of triphosphate nucleotides of DZNep and DZAri was observed.
      The mode of action of DZNep and DZAri appears complex, at least in part, at the
      level of infectivity as shown by decreases in syncytia formation in HIV-1
      infected H9 cells and at the level of transcription as both drugs inhibited the
      expression of basal or tat-induced HIV-1 long terminal repeat chloramphenicol
      acetyltransferase activity in stably transfected cell lines. Since DZNep induced
      in H9 cells a rapid expression of nuclear binding factors that recognize the AP-1
      transcription site, the anti-HIV-1 activity of the DZA analogs could partly be
      the induction of critical factors in the host cells. Thus, the 3-deazanucleoside
      drugs belong to an unusual class of anti-HIV-1 drugs, which may have therapeutic
      potential, in particular against AZT-resistant strains.

PMID- 7816822
TI  - The GTP-bound form of the yeast Ran/TC4 homologue blocks nuclear protein import
      and appearance of poly(A)+ RNA in the cytoplasm.
AB  - Ran/TC4, a Ras-like GTP-binding protein, and its nucleotide exchanger, RCC1, have
      been implicated in control of protein movement into the nucleus and cytoplasmic
      accumulation of mRNA. Saccharomyces cerevisiae contains two homologues of the
      mammalian Ran/TC4, encoded by the GSP1 and GSP2 genes. We have constructed yeast
      strains that overproduce either wild-type Gsp1 or a form of Gsp1 with glycine-21
      converted to valine (Gsp1-G21V), which we show stabilizes the GTP-bound form.
      Cells producing Gsp1-G21V have defects in localization of nuclear proteins;
      nuclear proteins accumulate in the cytoplasm following galactose induction of
      Gsp1-G21V. Similarly, cells producing Gsp1-G21V retain poly(A)+ RNA in their
      nuclei. These findings suggest that hydrolysis of GTP by Ran/TC4 is necessary for
      proper import of proteins into the nucleus and appearance of poly(A)+ RNA in the
      cytoplasm.

PMID- 7816823
TI  - The chemistry of eavesdropping, alarm, and deceit.
AB  - Arthropods that prey on or parasitize other arthropods frequently employ those
      chemical cues that reliably indicate the presence of their prey or hosts.
      Eavesdropping on the sex pheromone signals emitted to attract mates allows many
      predators and parasitoids to find and attack adult insects. The sex pheromones
      are also useful signals for egg parasitoids since eggs are frequently deposited
      on nearby plants soon after mating. When the larval stages of insects or other
      arthropods are the targets, a different foraging strategy is employed. The larvae
      are often chemically inconspicuous, but when they feed on plants the injured
      plants respond by producing and releasing defensive chemicals. These plant
      chemicals may also serve as "alarm signals" that are exploited by predators and
      parasitoids to locate their victims. There is considerable evidence that the
      volatile "alarm signals" are induced by interactions of substances from the
      herbivore with the damaged plant tissue. A very different strategy is employed by
      several groups of spiders that remain stationary and send out chemical signals
      that attract prey. Some of these spiders prey exclusively on male moths. They
      attract the males by emitting chemicals identical to the sex pheromones emitted
      by female moths. These few examples indicate the diversity of foraging strategies
      of arthropod predators and parasitoids. It is likely that many other interesting
      chemically mediated interactions between arthropod hunters and their victims
      remain to be discovered. Increased understanding of these systems will enable us
      to capitalize on natural interactions to develop more ecologically sound,
      environmentally safe methods for biological control of insect pests of
      agriculture.

PMID- 7816824
TI  - Identification, activity, and structural studies of peptides incorporating the
      phorbol ester-binding domain of protein kinase C.
AB  - The family of homologous enzymes known as protein kinase C (PKC) has been the
      object of intense interest because of its crucial role in cellular signal
      transduction. Although considerable information about the activation of PKC has
      been gained through structure-activity, molecular modeling, and synthetic studies
      of both natural and designed activators, information about the structure of PKC
      itself has been limited by its large size and requirement for phospholipid
      cofactors. Additionally, difficulties in the purification of truncated mutants of
      PKC have thus far prevented their analysis by nuclear magnetic resonance (NMR) or
      x-ray crystallographic methods. We describe the identification, synthesis, ligand
      binding analysis, cofactor requirements, and preliminary NMR evaluation of two
      subdomains (peptides B and C) of the regulatory domain of PKC-gamma. Peptides B
      and C bind [3H]phorbol 12,13-dibutyrate with good affinity (Kd = 6.4 microM and
      414 nM, respectively) in the presence of phosphatidylserine. In comparison, the
      binding affinity of [3H]phorbol 12,13-dibutyrate for PKC was found to be 2.6 nM.
      Like PKC itself, these peptides also recognize other PKC activators, including
      dioctanoylglycerol and teleocidin B-4, and exhibit an ability to differentiate
      phorbol ester from its C-4 epimer. NMR studies of PKC subdomains are also
      described, indicating that both peptides B and C are well behaved in solution and
      do not exhibit any concentration-dependent changes. Finally, these studies reveal
      that peptide B becomes conformationally ordered only in the presence of
      phospholipid, suggesting that the regulatory domain of PKC itself might be
      organized for activation only when associated with the lipid bilayer, where its
      activator (diacylglycerol) is encountered.

PMID- 7816825
TI  - Cladistic analyses of combined traditional and molecular data sets reveal an
      algal lineage.
AB  - The chromophyte algae are a large and biologically diverse assemblage of brown
      seaweeds, diatoms, and other golden algae classified in 13 taxonomic classes. One
      subgroup (diatoms, pedinellids, pelagophytes, silicoflagellates, and certain
      enigmatic genera) is characterized by a highly reduced flagellar apparatus. The
      flagellar apparatus lacks microtubular and fibrous roots, and the flagellum basal
      body is attached directly to the nucleus. We hypothesize that the flagellar
      reduction is the result of a single evolutionary series of events. Cladistic
      analysis of ultrastructural and biochemical data reveals a monophyletic group
      that unites all taxa with a reduced flagellar apparatus, supporting our
      hypothesis. Phylogenetic analyses of 18S rRNA gene sequence data provide strong
      resolution within most of the major groups of chromophytes but only weakly
      resolve relationships among those groups. Some of the molecularly based most
      parsimonious trees, however, also unite the taxa with a reduced flagellar
      apparatus, although the diatoms are not included in this lineage. This grouping
      is further supported by a posteriori character weighting of the molecular data,
      suggesting that flagellar reduction occurred at least twice in parallel
      evolutionary series of events. To further test our hypothesis of a single
      evolutionary reduction in the flagellar apparatus, we combine the two data sets
      and subject the hybrid data matrix to parsimony analysis. The resulting trees
      unite the diatoms with the other reduced flagellar apparatus algae in a
      monophyletic group. This result supports our hypothesis of a single evolutionary
      reduction and indicates the existence of a previously unrecognized lineage of
      algae characterized by a highly reduced flagellar apparatus. Further, this study
      suggests that the traditional classification of the diatoms with the chrysophytes
      and xanthophytes in the division (= phylum) Chrysophyta, as presented in most
      textbooks, is unsatisfactory and that a significantly different classification
      should be employed.

PMID- 7816826
TI  - Structure and function in rhodopsin: the fate of opsin formed upon the decay of
      light-activated metarhodopsin II in vitro.
AB  - We report that the light-activated bovine metarhodopsin II, upon decay, first
      forms opsin in the correctly folded form. The latter binds 11-cis-retinal and
      regenerates the native rhodopsin chromophore. However, when the opsin formed upon
      metarhodopsin II decay is kept in 0.1% dodecyl maltoside, it converts in a time
      dependent manner to a form(s) that does not bind 11-cis-retinal. On subsequent
      addition of 11-cis-retinal, slow reversal of the non-retinal-binding forms to the
      correctly folded retinal-binding form has been demonstrated. We have studied the
      influence, on the above interconversions, of pH, phospholipids (rod outer segment
      and soybean), dithiothreitol, and a mixture of reduced and oxidized glutathione.
      Chromophore regeneration in the presence of 11-cis-retinal was highest at pH 6.0
      6.3. The addition of dithiothreitol just before bleaching gave back only a small
      amount (7%) of rhodopsin on the subsequent addition of 11-cis-retinal, whereas
      the slow phase(s) of chromophore formation was completely abolished. The presence
      of a mixture of reduced and oxidized glutathione did not significantly affect the
      results. Addition of phospholipids, either from soybean or rod outer segment,
      prior to bleaching stabilized the initially formed opsin, resulting in much
      higher chromophore regeneration. However, addition of the phospholipids after
      conversion of the opsin to non-retinal-binding form(s) arrested the subsequent
      reversal of the opsin to the retinal-binding form.

PMID- 7816827
TI  - Cleavage of supercoiled plasmid DNA by autoantibody Fab fragment: application of
      the flow linear dichroism technique.
AB  - A highly effective method consisting of two affinity chromatography steps and ion
      exchange and gel-filtration chromatography steps was developed for purification
      of autoantibodies from human sera with DNA-hydrolyzing activity. Antibody Fab
      fragment, which had been purified 130-fold, was shown to catalyze plasmid DNA
      cleavage. The flow linear dichroism technique was used for quantitative and
      qualitative studying of supercoiled plasmid DNA cleavage by these autoantibodies
      in comparison with DNase I and EcoRI restriction endonuclease. The DNA
      autoantibody Fab fragment was shown to hydrolyze plasmid DNA by Mg(2+)-dependent
      single-strand multiple nicking of the substrate. Kinetic properties of the DNA
      autoantibody Fab fragment were evaluated from the flow linear dichroism and
      agarose gel electrophoresis data and revealed a high affinity (Kobsm = 43 nM) and
      considerable catalytic efficiency (kappcat/Kobsm = 0.32 min-1.nM-1) of the
      reaction.

PMID- 7816828
TI  - DNA damage and repair in telomeres: relation to aging.
AB  - We have established a method for the detection of DNA damage and its repair in
      human telomeres, the natural ends of chromosomes which are necessary for
      replication and critical for chromosomal stability. We find that ultraviolet
      light-induced pyrimidine dimers in telomeric DNA are repaired less efficiently
      than endogenous genes but more efficiently than inactive, noncoding regions. We
      have also measured telomeric length, telomeric DNA damage, and its repair in
      relation to the progression of aging. Telomeres are shorter in fibroblasts from
      an old donor compared to fibroblasts from a young donor, shortest in cells from a
      patient with the progeroid disorder Werner syndrome, and relatively long in
      fibroblasts from a patient with Alzheimer disease. Telomeric DNA repair
      efficiency is lower in cells from an old donor than in cells from a young donor,
      normal in Alzheimer cells, and slightly lower in Werner cells. It is possible
      that this decline in telomeric repair with aging is of functional significance to
      an age-related decline in genomic stability.

PMID- 7816829
TI  - Mapping the mouse ZP3 combining site for sperm by exon swapping and site-directed
      mutagenesis.
AB  - During fertilization in mice, sperm bind to mouse ZP3 (mZP3), a M(r)
      approximately 83,000 glycoprotein present in the ovulated egg extracellular coat,
      or zona pellucida. Sperm recognize and bind to specific serine/threonine-linked
      (O-linked) oligosaccharides present at the mZP3 combining site for sperm. Binding
      to mZP3 induces sperm to undergo a form of exocytosis, the acrosome reaction. To
      map the mZP3 combining site for sperm, we examined the effect of exon swapping
      and site-directed mutagenesis on the glycoprotein's two activities, sperm binding
      and induction of the acrosome reaction. Stably transfected embryonal carcinoma
      cell lines were established that synthesized recombinant glycoproteins and
      secreted them into the culture medium. The glycoproteins were partially purified
      from culture medium and assayed for sperm-binding and acrosome reaction-inducing
      activities. Results of these assays suggest that glycosylation of one or more of
      five serine residues, clustered together in a polypeptide region encoded by mZP3
      gene exon 7, is required for activity. Interestingly, this polypeptide region
      exhibits considerable sequence divergence during evolution and may be related to
      the proposed role for oligosaccharides in species-specific gamete adhesion during
      mammalian fertilization.

PMID- 7816830
TI  - Erythrocyte lipids in triose-phosphate isomerase deficiency.
AB  - Marked hypoalphalipoproteinemia was found together with relatively low serum
      cholesterol, triacylglycerol, and LDL levels in a triose-phosphate isomerase
      (TPI; D-glyceraldehyde-3-phosphate ketol-isomerase, EC 5.3.1.1)-deficient
      Hungarian family, especially in the two compound-heterozygote brothers. Apart
      from a slight increase in palmitic and stearic acids together with a slight
      decrease in oleic and linoleic acids, no other changes were found in the fatty
      acid composition of the erythrocyte phospholipids. Anisotropy measurements with n
      (9-anthroyloxy) stearic and -palmitic acid fluorophores revealed increased
      motional freedom of the fatty acid chains in the external lipid layers of the
      intact erythrocytes from all members of the TPI-deficient family as compared with
      normal age-matched controls. This asymmetric increase in membrane fluidity was
      found to be significantly higher in the propositus than in his compound
      heterozygote brother without any neurological disorders. The change in membrane
      fluidity may result from as-yet-unresolved aspects of the lipid composition of
      the plasma membrane. Our findings that the differences between the TPI-deficient
      individuals and normal controls and the differences between the two compound
      heterozygote brothers were all absent in the phospholipid extracts of the same
      erythrocytes favor the assumption that the increased motional freedom of the
      fatty acid chains in the external surface of the bilayer is caused by the binding
      of the mutant TPI molecule to the N-terminal sequence of band 3 protein.

PMID- 7816832
TI  - Basilar membrane resonance in the cochlea of the mustached bat.
AB  - The mustached bat (Pteronotus parnellii) detects the wing beats of prey insects
      by resolving small frequency modulations in the return echoes to the constant
      frequency component of its echolocation call at about 61 kHz. The fine frequency
      discrimination required for this task is due largely to the mechanical properties
      of the cochlea, as indicated indirectly by the presence of large otoacoustic
      emissions at 61 kHz. A laser diode interferometer was used to measure basilar
      membrane displacements in the basal turn of the cochlea at a location that is 4-6
      mm basal to the 61-kHz place on the basilar membrane. The region of the basilar
      membrane from which the measurements were made was tuned not only to those
      characteristic of this location (88-98 kHz) but also very sharply tuned to 61
      kHz. The 61-kHz tuning was labile and could be modeled as a simple resonance. The
      resonance is not restricted to the 61-kHz place but involves more basal regions.
      We also provide direct evidence to show that otoacoustic emissions from the ear
      propagate along the basilar membrane.

PMID- 7816831
TI  - Rapid induction of tumor necrosis factor alpha in the cerebrospinal fluid after
      intracerebroventricular injection of lipopolysaccharide revealed by a sensitive
      capture immuno-PCR assay.
AB  - Tumor necrosis factor alpha (TNF-alpha) is an important mediator in many
      pathophysiologic processes, both in the central nervous system (CNS) and in the
      periphery. For this study, we have designed a very sensitive immuno-PCR detection
      system to investigate the time course of TNF-alpha induction in the rat
      cerebrospinal fluid after intracerebroventricular administration of bacterial
      lipopolysaccharide (LPS). Immuno-PCR combines antibody specificity with PCR
      signal amplification and provides a sensitivity in the picomolar range. The
      enhanced sensitivity of this assay allowed the detection of TNF-alpha in the
      cerebrospinal fluid as early as 15 min after intracerebroventricular
      administration of LPS. The present results suggest that the ventricular
      compartment of the CNS, although confined within the blood-brain barrier, is
      highly responsive to proinflammatory stimuli such as LPS administration. Insight
      into the molecular mechanisms underlying this compartmentalization could be key
      to the pathology and treatment of many CNS diseases, especially the meningitides.

PMID- 7816833
TI  - Bidirectional interlocus concerted evolution following allopolyploid speciation
      in cotton (Gossypium).
AB  - Polyploidy is a prominent process in plant evolution; yet few data address the
      question of whether homeologous sequences evolve independently subsequent to
      polyploidization. We report on ribosomal DNA (rDNA) evolution in five
      allopolyploid (AD genome) species of cotton (Gossypium) and species representing
      their diploid progenitors (A genome, D genome). Sequence data from the internal
      transcribed spacer regions (ITS1 and ITS2) and the 5.8S gene indicate that rDNA
      arrays are homogeneous, or nearly so, in all diploids and allopolyploids
      examined. Because these arrays occur at four chromosomal loci in allopolyploid
      cotton, two in each subgenome, repeats from different arrays must have become
      homogenized by interlocus concerted evolution. Southern hybridization analysis
      combined with copy-number estimation demonstrate that this process has gone to
      completion in the diploids and to completion or near-completion in all
      allopolyploid species and that it most likely involves the entire rDNA repeat.
      Phylogenetic analysis demonstrates that interlocus concerted evolution has been
      bidirectional in allopolyploid species--i.e., rDNA from four polyploid lineages
      has been homogenized to a D genome repeat type, whereas sequences from Gossypium
      mustelinum have concerted to an A genome repeat type. Although little is known
      regarding the functional significance of interlocus concerted evolution of
      homeologous sequences, this study demonstrates that the process occurs for
      tandemly repeated sequences in diploid and polyploid plants. That interlocus
      concerted evolution can occur bidirectionally subsequent to hybidization and
      polyploidization has significant implications for phylogeny reconstruction,
      especially when based on rDNA sequences.

PMID- 7816834
TI  - A Staphylococcus aureus autolysin that has an N-acetylmuramoyl-L-alanine amidase
      domain and an endo-beta-N-acetylglucosaminidase domain: cloning, sequence
      analysis, and characterization.
AB  - The Tn551 insertion site of the autolysis-deficient Staphylococcus aureus mutant
      RUSAL2 was cloned and used to identify the autolysis gene atl in the parent
      strain, RN450. The open reading frame for atl was 3768 bp in length, encoding a
      deduced protein of 1256 amino acids and molecular size of 137,381 Da. The atl
      gene product is a bifunctional protein that has an amidase domain and an endo
      beta-N-acetylglucosaminidase domain which must undergo proteolytic processing to
      generate the two extracellular lytic enzymes found in the culture broth of S.
      aureus.

PMID- 7816836
TI  - Relation between oscillatory activity and long-range synchronization in cat
      visual cortex.
AB  - Recent theoretical studies have suggested that oscillatory firing patterns with
      frequencies in the gamma band (30-70 Hz) may be instrumental for the
      establishment of synchrony among widely distributed neurons if synchrony is to be
      achieved by reciprocal connections. We have now investigated the relationship
      between synchrony and oscillations in cat visual cortex. Our results show that
      when synchronization of neuronal activity occurs over distances of > 2 mm in
      primary visual cortex, or occurs between the two hemispheres, it is almost always
      associated with oscillatory firing patterns, whereas synchronization over short
      distances occurs also in the absence of oscillations. Furthermore, our results
      indicate that short-range interactions affect both the firing rate of the
      respective neurons and the timing of their discharges, whereas only the latter is
      influenced by long-range interactions. These data support the hypothesis that
      oscillatory activity can contribute to the establishment of long-range synchrony
      in a network of reciprocally coupled neurons.

PMID- 7816837
TI  - Can amino acid requirements for nutritional maintenance in adult humans be
      approximated from the amino acid composition of body mixed proteins?
AB  - The quantitative needs for the dietary indispensable amino acids in adult human
      protein nutrition are still poorly established. Tracer studies with 13C-labeled
      amino acids have been undertaken previously in our laboratories to reevaluate and
      further determine the minimum physiological needs for selected indispensable
      amino acids in healthy adult volunteers. For those amino acids that have not yet
      been studied by this approach we have proposed a tentative set of requirement
      figures based on considerations of the amino acid composition of body mixed
      proteins and the rate of obligatory amino acid losses (i.e., losses when the diet
      contains no proteins or amino acids). Here we provide an argument for, and a
      justification of, this approach as an interim measure until more comprehensive
      data become available on the quantitative aspects of amino acid metabolism in
      healthy humans.

PMID- 7816835
TI  - Polydnavirus-facilitated endoparasite protection against host immune defenses.
AB  - The polydnavirus of Campoletis sonorensis has evolved with an unusual life cycle
      in which the virus exists as an obligate symbiont with the parasite insect and
      causes significant physiological and developmental alterations in the parasite's
      host. The segmented polydnavirus genome consists of double-stranded superhelical
      molecules; each segment is apparently integrated into the chromosomal DNA of each
      male and female wasp. The virus replicates in the nucleus of calyx cells and is
      secreted into the oviduct. When the virus is transferred to the host insect
      during oviposition, gene expression induces host immunosuppression and
      developmental arrest, which ensures successful development of the immature
      endoparasite. In the host, polydnavirus expression is detected by 2 hr and during
      endoparasite development. Most of the abundantly expressed viral genes expressed
      very early after parasitization belong to multigene families. Among these
      families, the "cysteine-rich" gene family is the most studied, and it may be
      important in inducing host manifestations resulting in parasite survival. This
      gene family is characterized by a similar gene structure with introns at
      comparable positions within the 5' untranslated sequence and just 5' to a
      specific cysteine codon (*C) within a cysteine motif, C-*C-CC-C-C. Another
      unusual feature is that the nucleotide sequences of introns 2 in the subfamily
      WHv1.0/WHv1.6 are more conserved than those of the flanking exons. The structures
      of these viral genes and possible functions for their encoded protein are
      considered within the context of their endoparasite and virus strategy for
      genetic adaptation and successful parasitization.

PMID- 7816838
TI  - Virus-mediated or transgenic suppression of a G-protein alpha subunit and
      attenuation of fungal virulence.
AB  - Strains of the chestnut blight fungus Cryphonectria parasitica harboring RNA
      viruses of the genus Hypovirus exhibit significantly reduced levels of virulence
      (called hypovirulence). The accumulation of a heterotrimeric GTP-binding protein
      (G protein) alpha subunit of the Gi class was found to be reduced in hypovirus
      containing C. parasitica strains. Transgenic cosuppression, a phenomenon
      frequently observed in transgenic plants, reduced the accumulation of this alpha
      subunit in virus-free fungal strains. Significantly, the resulting transgenic
      fungal strains were also hypovirulent. These results indicate a crucial role for
      G-protein-linked signal transduction in fungal pathogenesis and suggest a
      molecular basis for virus-mediated attenuation of fungal virulence.

PMID- 7816839
TI  - Axial skeleton homeosis and forelimb malformations in Hoxd-11 mutant mice.
AB  - The Hoxd-11 gene was disrupted by homologous recombination in embryonic stem
      cells. We found that Hoxd-11-/- mutant mice are viable and display homeotic
      transformations of their sacral vertebrae, while their forelimbs present
      abnormalities of some metacarpals and of the first row of carpal bones. These
      results are discussed in the light of current models of tetrapod axial skeleton
      and limb patterning.

PMID- 7816840
TI  - Human immunodeficiency virus (HIV) antigens: structure and serology of
      multivalent human mucin MUC1-HIV V3 chimeric proteins.
AB  - Molecular modeling and two-dimensional NMR techniques enable us to identify
      structural features in the third variable region (V3) loop of the human
      immunodeficiency virus (HIV) surface glycoprotein gp120, in particular the
      principal neutralizing determinant (PND), that remain conserved despite the
      sequence variation. The conserved structure of the PND is a solvent-accessible
      protruding motif or a knob, structurally isomorphous with the immunodominant
      knobs in the tandem repeat protein of human mucin 1 (MUC1) (a tumor antigen for
      breast, pancreatic, and ovarian cancer). We have replaced the mucin antigenic
      knobs by the PND knobs of the HIV MN isolate in a set of chimeric human MUC1/HIV
      V3 antigens. This produced multivalent HIV antigens in which PNDs are located at
      regular intervals and separated by extended mucin spacers. In this article we
      show by two-dimensional NMR spectroscopy that the multivalent antigens preserve
      the PNDs in their native structure. We also demonstrate by ELISA that the
      antigens correctly present the PNDs for binding to monoclonal antibodies or
      polyclonal antisera from HIV-infected patients.

PMID- 7816841
TI  - DNA-dependent protein kinase activity is absent in xrs-6 cells: implications for
      site-specific recombination and DNA double-strand break repair.
AB  - DNA-dependent protein kinase (DNA-PK) is a nuclear serine/threonine protein
      kinase composed of a catalytic subunit called p350 and a DNA binding component
      termed Ku. Ku consists of two tightly associated polypeptides of approximately 70
      kDa and 80 kDa (Ku80). An intriguing feature of DNA-PK is that it binds to DNA
      ends and other discontinuities in DNA and requires these structures for its
      activation. This suggests that DNA-PK may function in DNA repair and/or
      recombination. Consistent with this, Ku DNA binding activity was shown recently
      to be absent in extracts of hamster xrs-6 cells, which are defective in DNA
      double-strand (ds) break repair and V(D)J recombination. Furthermore, xrs-6 cells
      are complemented by expression of the Ku80 cDNA. To date, DNA-PK activity has
      been demonstrated unequivocally only in extracts of primate cells. Here, we
      describe an assay that can detect DNA-PK activity in extracts of mouse, hamster,
      Xenopus, and Drosophila cells. Using this assay, we find that xrs-6 cells
      completely lack DNA-PK activity. By contrast, xrs-6 derivatives complemented by
      human chromosome fragments bearing the Ku80 gene have restored both the DNA end
      binding and kinase activities associated with DNA-PK. Finally, we show that xrs-6
      extracts are complemented biochemically by purified Ku. Our findings indicate
      that the xrs-6 defects are direct consequences of the mutation in Ku80 and
      implicate DNA-PK in recombination and DNA repair processes.

PMID- 7816842
TI  - A test of lattice protein folding algorithms.
AB  - We report a blind test of lattice-model-based search strategies for finding
      global minima of model protein chains. One of us (E.I.S.) selected 10 compact
      conformations of 48-mer chains on the three-dimensional cubic lattice and used
      their inverse folding algorithm to design HP (H, hydrophobic; P, polar) sequences
      that should fold to those "target" structures. The sequences, but not the
      structures, were sent to the UCSF group (K.Y., K.M.F., P.D.T., H.S.C., and
      K.A.D.), who used two methods to attempt to find the globally optimal
      conformations: "hydrophobic zippers" and a constraint-based hydrophobic core
      construction (CHCC) method. The CHCC method found global minima in all cases, and
      the hydrophobic zippers method found global minima in some cases, in minutes to
      hours on workstations. In 9 out of 10 sequences, the CHCC method found lower
      energy conformations than the 48-mers were designed to fold to. Thus the search
      strategies succeed for the HP model but the design strategy does not. For every
      sequence the global energy minimum was found to have multiple degeneracy with
      10(3) to 10(6) conformations. We discuss the implications of these results for
      (i) searching conformational spaces of simple models of proteins and (ii) how
      these simple models relate to proteins.

PMID- 7816843
TI  - DNA alterations detected in the progeny of paternally irradiated Japanese medaka
      fish (Oryzias latipes).
AB  - A nonmammalian test system for germ-cell mutagenesis has been developed by using
      the Japanese medaka fish. We describe a system for detecting DNA alterations in
      F1 progeny descended from the gamma-irradiated male medaka that uses an
      arbitrarily primed polymerase chain reaction and fingerprinting. A combination of
      these two methods has some advantages for screening changes in genomic DNA of
      individual progeny because this detection system can (i) screen for mutational
      events before embryos with dominant lethal mutations are eliminated during
      development and (ii) detect DNA changes in the progeny of irradiated males
      without functional selection and bias, such as resistance to chemicals. DNA
      alterations are detected as changes in patterns (i.e., band loss and/or band
      gain) of DNA fingerprints of progeny descended from males whose spermatozoa or
      spermatids were gamma-irradiated (4.75 or 9.50 Gy). We determined the frequency
      of gamma-irradiation-induced band loss in arbitrarily primed polymerase chain
      reaction fingerprints of DNA from severely malformed embryos with dominant lethal
      mutations and hatched viable embryos. The frequency of band loss in both dominant
      lethal embryos and hatched viable embryos increased with increasing gamma-ray
      dose, although more so in the former. We detected a new band in the fingerprints
      as a heritable DNA alteration but not a viability- or phenotype-affecting DNA
      alteration in two viable mutants recovered after gamma-irradiation experiments. A
      cloned amplified fragment of the new band contained a repeated sequence of
      p(ATGT)n.

PMID- 7816845
TI  - The chemistry of gamete attraction: chemical structures, biosynthesis, and
      (a)biotic degradation of algal pheromones.
AB  - Female gametes of marine brown algae release and/or attract their conspecific
      males by chemical signals. The majority of these compounds are unsaturated,
      nonfunctionalized acyclic, and/or alicyclic C11 hydrocarbons. Threshold
      concentrations for release and attraction are generally observed in the range of
      1-1000 pmol. The blends may contain various configurational isomers of the
      genuine pheromones as well as mixtures of enantiomers. Higher plants produce the
      C11 hydrocarbons from dodeca-3,6,9-trienoic acid; brown algae exploit the family
      of icosanoids for biosynthesis of the same compounds. The biosynthetic routes
      comprise several spontaneously occurring pericyclic reactions such as [3.3]
      sigmatropic rearrangements, [1.7]-hydrogen shifts, and electrocyclic ring
      closures. All pheromones are (a)biotically degraded by ubiquitous oxidative
      pathways involving singlet oxygen or hydroxyl radicals, which may be produced
      through the agency of heavy metals, huminic acids, or light.

PMID- 7816844
TI  - Binding of an invariant-chain peptide, CLIP, to I-A major histocompatibility
      complex class II molecules.
AB  - Invariant chain (Ii) associates with major histocompatibility complex (MHC) class
      II molecules and is crucial for antigen presentation by class II molecules. The
      exact nature of Ii interaction with MHC class II molecules remains undefined. A
      nested set of Ii peptides, CLIPs (class II-associated Ii peptides), have been
      eluted from various MHC class II molecules, suggesting that CLIPs correspond, at
      least in part, to the Ii motif which blocks the conventional peptide binding site
      in MHC class II molecules. Here we report how CLIPs interact with class II MHC
      molecules, I-A. We have identified regions critical for binding of CLIPs and I-A
      class II molecules. In most cases, the binding of CLIPs to a number of I-A
      molecules is modulated by the steric bulk of methionine residues at positions 93
      and 99. In addition, the binding of CLIPs to an I-A molecule, I-Au, is sensitive
      to substitutions at aspartic acid-59 in the alpha chain and threonine-86 in the
      beta chain, whereas the binding of an antigen-derived peptide is not. Taken
      together, these results provide an insight as to how CLIPs bind to MHC class II
      heterodimers.

PMID- 7816846
TI  - Chemistry of sex attraction.
AB  - The chemical communication system used to attract mates involves not only the
      overt chemical signals but also indirectly a great deal of chemistry in the
      emitter and receiver. As an example, in emitting female moths, this includes
      enzymes (and cofactors, mRNA, genes) of the pheromone biosynthetic pathways,
      hormones (and genes) involved in controlling pheromone production, receptors and
      second messengers for the hormones, and host plant cues that control release of
      the hormone. In receiving male moths, this includes the chemistry of pheromone
      transportation in antennal olfactory hairs (binding proteins and sensillar
      esterases) and the chemistry of signal transduction, which includes specific
      dendritic pheromone receptors and a rapid inositol triphosphate second messenger
      signal. A fluctuating plume structure is an integral part of the signal since the
      antennal receptors need intermittent stimulation to sustain upwind flight. Input
      from the hundreds of thousands of sensory cells is processed and integrated with
      other modalities in the central nervous system, but many unknown factors modulate
      the information before it is fed to motor neurons for behavioral responses. An
      unknown brain control center for pheromone perception is discussed relative to
      data from behavioral-threshold studies showing modulation by biogenic amines,
      such as octopamine and serotonin, from genetic studies on pheromone
      discrimination, and from behavioral and electrophysiological studies with
      behavioral antagonists.

PMID- 7816847
TI  - The chemistry of sexual selection.
AB  - The moth Utetheisa ornatrix (Lepidoptera: Arctiidae) is protected against
      predation by pyrrolizidine alkaloids that it sequesters as a larva from its
      foodplants. At mating, the male transfers alkaloid to the female with the
      spermatophore, a gift that the female supplements with alkaloid of her own and
      transmits to the eggs. Eggs are protected as a result. The male produces a
      pheromone, hydroxydanaidal, that he derives from the alkaloid and emits from a
      pair of extrusible brushes (coremata) during precopulatory interaction with the
      female. Males rendered experimentally alkaloid-free fail to produce the pheromone
      and are less successful in courtship. The male produces the pheromone in
      proportion both to his alkaloid load and to the amount of alkaloid he transfers
      to the female. The pheromone could thus serve as an indication of male "worth"
      and provide a basis for female choice. Utetheisa females are promiscuous and
      therefore are able to accrue multiple nuptial gifts (alkaloid and nutrient, both
      transmitted with the spermatophore). They use sperm selectively, favoring those
      of larger males. Larger males in nature are also richer in alkaloid. Females
      therefore reinforce after copulation the choice mechanism they already exercise
      during courtship.

PMID- 7816848
TI  - Chemical signals in the marine environment: dispersal, detection, and temporal
      signal analysis.
AB  - Chemical signals connect most of life's processes, including interorganismal
      relationships. Detection of chemical signals involves not only recognition of a
      spectrum of unique compounds or mixtures of compounds but also their spatial and
      temporal distribution. Both spectral and temporal signal processing determine
      what is a signal and what is background noise. Each animal extracts its unique
      information from the chemical world and uniquely contributes to it. Lobsters have
      provided important information on temporal signal processing. Marine chemical
      signals can be measured with high spatio-temporal resolution giving us a novel
      view of the lobster's environment. Lobster chemoreceptor cells have flicker
      fusion frequencies of 4 Hz and can integrate stimuli over 200 ms, closely
      corresponding to odor sampling behavior with 4-Hz "sniffs." Using this
      information, spatial odor gradients can be determined from temporal analysis of
      odor patches typical of turbulent dispersal. Lobsters appear to use this
      information to locate odor sources. Lobster social behavior depends greatly on
      chemical signals. Urine carries important information for courtship, dominance,
      and individual recognition. A novel gland in the nephropore is strategically
      located to release its products into the urine. Urine, in turn, is injected into
      the gill current, which jets water 1-2 m ahead of the animal. Lobsters control
      three different currents that carry chemical signals to and from them. The study
      of odor dynamics has only just begun. It will be exciting to see how signal
      dispersal, receptor temporal tuning, neural processing, and animal behavior
      interact to enhance signals for communication and detection and to reduce signals
      for chemical camouflage.

PMID- 7816849
TI  - Analysis of chemical signals by nervous systems.
AB  - Intraspecific and interspecific communication and recognition depend on olfaction
      in widely diverse species of animals. Olfaction, an ancient sensory modality, is
      based on principles of neural organization and function that appear to be
      remarkably similar throughout the zoosphere. Thus, the "primitives" of olfactory
      stimuli that determine the input information of olfaction, the kinds of
      "molecular images" formed at various levels in the olfactory pathway, and the
      cellular mechanisms that underlie olfactory information processing are comparable
      in invertebrates and vertebrates alike. A case in point is the male-specific
      olfactory subsystem in moths, which is specialized to detect and analyze the
      qualitative, quantitative, and temporal features of the con-specific females' sex
      pheromonal chemical signal. This olfactory subsystem can be viewed, and is here
      presented, as a model in which common principles of organization and function of
      olfactory systems in general are exaggerated to serve the requirements of a
      chemical communication system that is crucial for reproductive success.

PMID- 7816851
TI  - From mutation mapping to phenotype cloning.

PMID- 7816850
TI  - Chemical ecology: a view from the pharmaceutical industry.
AB  - Biological diversity reflects an underlying molecular diversity. The molecules
      found in nature may be regarded as solutions to challenges that have been
      confronted and overcome during molecular evolution. As our understanding of these
      solutions deepens, the efficiency with which we can discover and/or design new
      treatments for human disease grows. Nature assists our drug discovery efforts in
      a variety of ways. Some compounds synthesized by microorganisms and plants are
      used directly as drugs. Human genetic variations that predispose to (or protect
      against) certain diseases may point to important drug targets. Organisms that
      manipulate molecules within us to their benefit also may help us to recognize key
      biochemical control points. Drug design efforts are expedited by knowledge of the
      biochemistry of a target. To supplement this knowledge, we screen compounds from
      sources selected to maximize molecular diversity. Organisms known to manipulate
      biochemical pathways of other organisms can be sources of particular interest. By
      using high throughput assays, pharmaceutical companies can rapidly scan the
      contents of tens of thousands of extracts of microorganisms, plants, and insects.
      A screen may be designed to search for compounds that affect the activity of an
      individual targeted human receptor, enzyme, or ion channel, or the screen might
      be designed to capture compounds that affect any step in a targeted metabolic or
      biochemical signaling pathway. While a natural product discovered by such a
      screen will itself only rarely become a drug (its potency, selectivity,
      bioavailability, and/or stability may be inadequate), it may suggest a type of
      structure that would interact with the target, serving as a point of departure
      for a medicinal chemistry effort--i.e., it may be a "lead." It is still beyond
      our capability to design, routinely, such lead structures, based simply upon
      knowledge of the structure of our target. However, if a drug discovery target
      contains regions of structure homologous to that in other proteins, structures
      known to interact with those proteins may prove useful as leads for a medicinal
      chemistry effort. The specificity of a lead for a target may be optimized by
      directing structural variation to specificity-determining sites and away from
      those sites required for interaction with conserved features of the targeted
      protein structure. Strategies that facilitate recognition and exploration of
      sites at which variation is most likely to generate a novel function increase the
      efficiency with which useful molecules can be created.

PMID- 7816852
TI  - Intrahelical ion pairs in intermediate filaments.

PMID- 7816853
TI  - Screening for mutations by enzyme mismatch cleavage with T4 endonuclease VII.
AB  - Each of four possible sets of mismatches (G.A/C.T, C.C/G.G, A.A/T.T, and C.A/G.T)
      containing the 8 possible single-base-pair mismatches derived from isolated
      mutations were examined to test the ability of T4 endonuclease VII to
      consistently detect mismatches in heteroduplexes. At least two examples of each
      set of mismatches were studied for cleavage in the complementary pairs of
      heteroduplexes formed between normal and mutant DNA. Four deletion mutations were
      also included in this study. The various PCR-derived products used in the
      formation of heteroduplexes ranged from 133 to 1502 bp. At least one example of
      each set showed cleavage of at least one strand containing a mismatch. Cleavage
      of at least one strand of the pairs of heteroduplexes occurred in 17 of the 18
      known single-base-pair mutations tested, with an A.A/T.T set not being cleaved in
      any mismatched strand. We propose that this method may be effective in detecting
      and positioning almost all mutational changes when DNA is screened for mutations.

PMID- 7816854
TI  - The chemistry of poisons in amphibian skin.
AB  - Poisons are common in nature, where they often serve the organism in chemical
      defense. Such poisons either are produced de novo or are sequestered from dietary
      sources or symbiotic organisms. Among vertebrates, amphibians are notable for the
      wide range of noxious agents that are contained in granular skin glands. These
      compounds include amines, peptides, proteins, steroids, and both water-soluble
      and lipid-soluble alkaloids. With the exception of the alkaloids, most seem to be
      produced de novo by the amphibian. The skin of amphibians contains many
      structural classes of alkaloids previously unknown in nature. These include the
      batrachotoxins, which have recently been discovered to also occur in skin and
      feathers of a bird, the histrionicotoxins, the gephyrotoxins, the
      decahydroquinolines, the pumiliotoxins and homopumiliotoxins, epibatidine, and
      the samandarines. Some amphibian skin alkaloids are clearly sequestered from the
      diet, which consists mainly of small arthropods. These include pyrrolizidine and
      indolizidine alkaloids from ants, tricyclic coccinellines from beetles, and
      pyrrolizidine oximes, presumably from millipedes. The sources of other alkaloids
      in amphibian skin, including the batrachotoxins, the decahydroquinolines, the
      histrionicotoxins, the pumiliotoxins, and epibatidine, are unknown. While it is
      possible that these are produced de novo or by symbiotic microorganisms, it
      appears more likely that they are sequestered by the amphibians from as yet
      unknown dietary sources.

PMID- 7816855
TI  - The importance of intramolecular ion pairing in intermediate filaments.
AB  - Nuclear and cytoskeletal networks of 10-nm intermediate filaments (IFs) are
      probably ubiquitous in multicellular eukaryotes. They likely play a role in
      maintaining the mechanical integrity of a cell. With the exception of the nuclear
      lamins, IF proteins can form IFs in vitro in the absence of cofactors or
      associated proteins. Below we present data suggesting that the large alpha
      helical "rod" domains of IF proteins are stabilized by large numbers (up to 50)
      of intra-helical ion pairs formed by residues of opposite charge situated four
      residues apart. These many ion pairs, sometimes involving up to 30% of the
      residues within a coiled-coil IF segment, can potentially contribute as much as
      10-25 kcal/mol (1 kcal = 4.18 kJ) to the stability of a single alpha-helical rod.
      Such stabilization is likely to play a major role in the chemical and physical
      stability of IF networks in vitro and in vivo. An investigation of other coiled
      coil proteins shows that selection for intrahelical ion pairing is not simply a
      property intrinsic to coiled-coil proteins. Rather, there is a correlation
      between the degree to which there is selection for intrahelical ion pairs and the
      extent to which a coiled-coil protein participates in highly ordered
      multimolecular interactions--e.g., as in IFs and myosin thick filaments. The
      propensity of putative ion pairs in some IF proteins--e.g., epidermal keratins-
      suggests that an underlying structural stability at the level of the monomer may
      play an important role in the extraordinary stability of dimers and higher
      ordered structures in cytoplasmic IFs.

PMID- 7816856
TI  - Conformational implications of asparagine-linked glycosylation.
AB  - The effects of cotranslational protein modification on the process of protein
      folding are poorly understood. Time-resolved fluorescence energy transfer has
      been used to assess the impact of glycosylation on the conformational dynamics of
      flexible oligopeptides. The peptide sequences examined are selected from
      glycoproteins of known three-dimensional structure. The energy transfer
      modulation associated with N-linked glycosylation is consistent with the
      glycopeptides sampling different conformational profiles in water. Results show
      that glycosylation causes the modified peptides to adopt a different ensemble of
      conformations, and for some peptides this change may lead to conformations that
      are more compact and better approximate the conformation of these peptides in the
      final folded protein. This result further implies that cotranslational
      glycosylation can trigger the timely formation of structural nucleation elements
      and thus assist in the complex process of protein folding.

PMID- 7816857
TI  - Pharmacological evaluation of methylcarbamylcholine-induced drinking behavior in
      rats.
AB  - Methylcarbamylcholine (MCC), a structural analog of carbachol (an acetylcholine
      agonist), has been reported to be a specific nicotinic cholinergic receptor
      ligand. MCC produces a robust polydipsic response shortly following central
      administration. The purpose of the present study was to pharmacologically
      characterize this increase in drinking behavior. Male Wistar rats were implanted
      with intracerebroventricular (ICV) cannula guides directed at the left lateral
      ventricle. Following a recovery period, animals were injected ICV with saline or
      various doses of MCC (3-60 micrograms) and water consumption was quantified. MCC
      produced a dose-related, transient increase in water consumption that peaked at a
      dose of 30 micrograms. In contrast, nicotine, a potent nicotinic cholinergic
      receptor agonist, did not produce changes in drinking following ICV
      administration. MCC-induced increases in drinking were not blocked by
      pretreatment with several selective nicotinic receptor antagonists including
      dihydro-beta-erythriodine (DHBE), hexamethonium, and mecamylamine. However,
      pretreatment with the muscarinic antagonist atropine (0.01 or 1.0 microgram)
      completely abolished MCC-induced polydipsia. Following a chronic treatment
      regimen (MCC injected ICV twice daily for 10 days), no tolerance to MCC-induced
      changes in water consumption was observed. Previous studies have demonstrated
      that tolerance develops to nicotinic-receptor mediated responses following the
      identical chronic treatment paradigm. These results suggest that MCC-induced
      polydipsia is mediated through stimulation of muscarinic rather than nicotinic
      receptors.

PMID- 7816858
TI  - High doses of oxytocin cause sedation and low doses cause an anxiolytic-like
      effect in male rats.
AB  - The aim of the present investigation was to explore dose relationships for
      effects of oxytocin on spontaneous motor activity in the rat. Oxytocin in doses
      from 1-1000 micrograms/kg was given SC to male Sprague-Dawley rats, and
      spontaneous motor behavior was measured by means of photocell-operated open-field
      observations. In the rats treated with low doses of oxytocin (1-4 micrograms/kg),
      there was a decrease in peripheral locomotor activity. With increasing doses (250
      1000 micrograms/kg), there were clear signs of sedative effects as indicated by a
      suppression of locomotor activity and rearing. The time course for the effect of
      oxytocin on peripheral activity (1 microgram/kg) and rearing (1 mg/kg) was
      tested. A maximal effect was obtained within 1 h and, thereafter, the behavior
      gradually returned to normal within 24 h. This spectrum of effects caused by
      oxytocin was similar to that of midazolam but different from that induced by
      raclopride.

PMID- 7816859
TI  - Serotonergic properties of cocaine: effects on a 5-HT2 receptor-mediated behavior
      and on extracellular concentrations of serotonin and dopamine.
AB  - The present study examined the ability of cocaine to produce behavioral and
      neuropharmacological effects through serotonin (5-HT) systems. Pretreatment with
      fluoxetine or cocaine potentiated the head-shake response to the 5-HT precursor,
      5-hydroxytryptophan (5-HTP; 75 mg/kg), a behavior mediated by the activation of 5
      HT2 receptors. This effect was antagonized by the selective 5-HT2 receptor
      antagonist ketanserin (1 mg/kg). In contrast, pretreatment with the selective
      norepinephrine uptake inhibitor desipramine (10 mg/kg) or the selective dopamine
      (DA) uptake inhibitor GBR 12909 (32 mg/kg) failed to potentiate the head-shake
      response. The effects of cocaine on extracellular concentrations of DA and 5-HT
      in the nucleus accumbens were examined using in vivo microdialysis in a separate
      group of anesthetized rats. Cocaine (10 mg/kg) increased the extracellular
      concentrations of DA and 5-HT by 300-350% over baseline levels. Cocaine's ability
      to increase the head-shake response and to increase extracellular concentrations
      of 5-HT may be due to its ability to block 5-HT uptake.

PMID- 7816860
TI  - Interactions of clozapine with the stimulus effects of DOM and LSD.
AB  - Two groups of rats were trained with the 5-HT2 agonists 2,5-dimethoxy-4
      methylamphetamine (DOM) or lysergic acid diethylamide (LSD) in a two-lever
      discrimination task. Tests of generalization and antagonism were then carried out
      with clozapine. DOM did not generalize to clozapine. Partial antagonism of DOM
      was observed with 0.3, 1, and 2 mg/kg clozapine and statistically significant
      full antagonism with 3 mg/kg. LSD did not fully generalize to clozapine. Partial
      antagonism of LSD was observed with 3 and 4 mg/kg clozapine. Because clozapine is
      known to block muscarinic as well as 5-HT2 receptors, atropine was studied in DOM
      trained rats. DOM partially generalized to 3 mg/kg atropine. Partial attenuation
      of DOM stimulus effects was observed with 3 mg/kg atropine, and no attenuation
      with 5 mg/kg. A combination of 2 mg/kg clozapine and 3 mg/kg atropine vs. DOM
      produced response suppression in five of seven rats. The atropine test results do
      not exclude the possibility of an antimuscarinic component in the observed
      attenuation of DOM and LSD stimulus effects by clozapine.

PMID- 7816861
TI  - Fluoxetine-induced inhibition of male rat copulatory behavior: modification by
      lesions of the nucleus paragigantocellularis.
AB  - In Experiment 1, the 5-HT uptake blocker fluoxetine (FLX; 20 mg/kg) reduced the
      proportion of sexually experienced male rats displaying ejaculations. Among those
      animals that did ejaculate there was an increase in intromission frequency (IF),
      ejaculation latency (EL), and postejaculatory interval (PEI) and a reduction in
      copulatory efficiency (CE) during the final copulatory sequence prior to sexual
      exhaustion. In Experiment 2, we found similar inhibitory effects of FLX as well
      as facilitating effects of lesions of the nucleus paragigantocellularis (PGi) on
      male rat copulatory behavior. Males with PGi lesions displayed more ejaculations
      and a longer latency to sexual exhaustion compared to intact animals. When FLX
      was given to rats with PGi lesions, it did not influence the proportion of rats
      ejaculating nor did it alter IF, EL, or PEI during the final copulatory series
      prior to exhaustion. These findings suggest that the inhibitory influences of FLX
      on male rat copulatory behavior are mediated in part by the interaction of FLX
      with neurons originating in the PGi.

PMID- 7816862
TI  - Involvement of 5-HT2 receptors in posthypoxic stimulus-sensitive myoclonus in
      rats.
AB  - We have previously reported that rats exhibited audiogenic myoclonus at 3 days
      after cardiac arrest. This phenomenon peaked at 14 days, gradually tapered off at
      older ages, and disappeared in most rats by 60 days following cardiac arrest.
      Because treatment with the 5-HT2-selective agonist, (+/-)-1-2,5-dimethoxy-4
      iodophenyl-2-aminopropane (DOI) significantly attenuated audiogenic myoclonus in
      these postcardiac-arrest rats, the involvement of 5-HT2 receptors in posthypoxic
      stimulus-sensitive myoclonus was suggested. In the current study, we, therefore,
      examined the binding properties of 5-HT2 receptors in the rat bain at various
      time points following cardiac arrest. The affinity constant of [3H]ketanserin
      binding to 5-HT2 receptors in cortical membranes of rats did not change. In
      contrast, Bmax values were found to be reduced at 3 and 14 days after cardiac
      arrest with some recovery after 60 days. Taken together with previous results,
      these results indicate that hypoactivity of central 5-HT2 neurotransmission may
      underlie the development of posthypoxic stimulus-sensitive myoclonus in rats.

PMID- 7816863
TI  - Beta 2- but not beta 1-adrenoceptors are involved in desipramine enhancement of
      aggressive behavior in long-term isolated mice.
AB  - The effects of several beta-adrenoceptor antagonists on the desipramine-induced
      increase in aggressive behavior in long-term isolated mice were examined.
      Desipramine HCl (10 mg/kg, IP) significantly increased the duration of aggressive
      behavior in isolated mice but did not significantly change the latency to the
      first attack consistent with our previous reports. Intraperitoneal administration
      of (+/- )propranolol HCl (2.5-10 mg/kg), a nonselective beta-adrenoceptor
      antagonist, dose dependently attenuated the desipramine-induced enhancement of
      aggressive behavior without significantly affecting the basal aggressive
      responses. ICI118,551 HCl (1.25-5 mg/kg, IP), a selective beta 2-adrenoceptor
      antagonist, also blocked the desipramine-induced enhancement of aggressive
      behavior in a dose-dependent manner, whereas metoprolol tartrate (5-20 mg/kg,
      IP), a selective beta 1-adrenoceptor antagonist, did not affect it. Moreover,
      clenbuterol HCl (0.1-0.5 mg/kg, IP), a lipophilic beta 2-adrenoceptor agonist,
      significantly increased the duration of basal aggressive behavior. Taken together
      with our previous finding that the desipramine-induced enhancement of aggressive
      behavior can be blocked by yohimbine, an alpha 2-adrenoceptor antagonist, the
      present results indicate that not only alpha 2- but also beta 2-adrenoceptor
      stimulation plays important roles in modulation of aggressive behavior in long
      term isolated mice.

PMID- 7816865
TI  - Methadone and feeding: sources of differences between home cage and operant
      chamber assessment procedures.
AB  - Methadone administration is reported to increase food intake in studies examining
      free feeding and to decrease food reinforced operant responding. In light of this
      apparent paradox, the present study evaluated methadone's effects on food
      reinforced operant responding under conditions more typical of free feeding
      studies than operant studies. The effect of methadone (5 mg/kg) on food intake
      was examined in rats maintained at 100% of their free feeding weights. Methadone
      did not increase food intake with food available under a fixed ratio 1 (FR 1)
      reinforcement schedule. Methadone did not alter response rate when each lever
      press produced a larger reinforcer (225 mg as opposed to 45 mg), but did increase
      food intake. When response requirements were changed from lever pressing to
      interruption of an infrared beam, increases in food intake following methadone
      administration were observed. Thus, the differences between methadone's effects
      on free feeding vs. operant chamber food intake may be due to procedural factors
      such as magnitude of reinforcement and response requirements.

PMID- 7816864
TI  - Heterogeneity of CCK-B receptors involved in animal models of anxiety.
AB  - The effects of the selective CCK-B agonists, BC 264 and BC 197, and the
      nonselective CCK agonist BDNL were investigated in the elevated plus-maze in
      rats. BDNL and BC 197 induced anxiogeniclike effects, in contrast to BC 264,
      which had no effect. The behavioral responses induced by BDNL were not
      significantly blocked by L-365,260, but were suppressed by CI-988, another
      selective CCK-B antagonist, and by high doses of L-364,718, a selective CCK-A
      antagonist. BC 197-induced effects were also blocked by CI-988. Competition
      experiments performed with [3H]pBC 264 using brain membranes of guinea pig,
      mouse, and rat were significantly better fitted when analyzed by a two site model
      than by a one site model with BC 197 but not with BC 264. Moreover, BC 264
      produced anxiogeniclike effects when administered with increasing doses of L
      365,260 and opposing effects with increasing doses of CI-988. Together these
      results give pharmacological and behavioral evidence for the existence of CCK-B
      receptor subtypes.

PMID- 7816866
TI  - Conditioned apomorphine-induced turning in 6-OHDA-lesioned rats.
AB  - Apomorphine-induced turning has been used to evaluate the extent of unilateral
      nigrostriatal denervation after 6-hydroxydopamine (6-OHDA) lesions and subsequent
      functional striatal reinnervation by catecholaminergic grafts. It has been noted
      that the pregraft rotational pattern is usually double peaked and that fetal
      ventral mesencephalic grafts or dopaminergic drugs will alter the second peak but
      leave the first relatively unchanged. We hypothesized that the first peak may be
      the result of factors extrinsic to the nigrostriatal dopamine system,
      specifically a conditioned turning response, and would, therefore, be unperturbed
      by the above treatments which increase dopaminergic (DA) inputs. This was
      investigated by injecting 6-OHDA, unilaterally, into the nigrostriatal pathway of
      several groups of young Fisher 344 rats. One experimental group was repeatedly
      tested with 0.05 mg/kg apomorphine and the rotations quantified. A second group
      received similar injections of apomorphine but were prevented from rotating.
      Vehicle control animals were also studied for both of the above experimental
      groups. Subsequent to the above treatment, all animals were tested unrestrained
      repeatedly on apomorphine. Our results support the conditioned response
      hypothesis in that the first peak is not present with the initial unrestrained
      apomorphine behavioral trial but is present upon the second and subsequent
      unrestrained trials. Moreover, the restrained but apomorphine-injected rats, as
      well as the control animals, manifest no first peak upon their first freely
      moving apomorphine test; the second and subsequent unrestrained apomorphine
      trials, in these groups, do manifest a first peak.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7816867
TI  - Accumbens D2 modulation of sensorimotor gating in rats: assessing anatomical
      localization.
AB  - The normal reduction in acoustic startle amplitude caused by a weak prepulse
      (prepulse inhibition; PPI) is deficient in schizophrenic patients and in rats
      after systemic or intraaccumbens treatment with the D2 dopamine agonist
      quinpirole. We examined the anatomical substrates of the PPI-disruptive effects
      of intraaccumbens quinpirole. PPI was significantly reduced in a dose-dependent
      manner by quinpirole infusion into the medial accumbens shell region, the lateral
      accumbens core region, and an intermediate central region. There was a weak
      tendency for this quinpirole effect to be more pronounced in core and central
      accumbens regions than in the medial and anteromedial accumbens. Using the
      retrograde tracer Nuclear yellow, shell and core regions were verified to receive
      different patterns of limbic cortical innervation. Although the accumbens appears
      to have a complex and functionally diversified intrinsic anatomy, the accumbens
      D2 modulation of sensorimotor gating appears to be distributed across several
      different accumbens subregions.

PMID- 7816868
TI  - Time course of dopamine1,2 and serotonin2 receptor binding of antipsychotics in
      vivo.
AB  - An in vivo receptor binding technique was applied to evaluate the affinities of
      clozapine (20 mg/kg), RMI-81582 (20 mg/kg), and haloperidol (1 mg/kg) for
      dopamine D1, D2 and serotonin 5-HT2 receptors in rat brain with [3H]-SCH23390,
      [3H]-YM-09151-2, and [3H]-ketanserin as selective ligands. The time course study
      of receptor occupancy at 25 to 250 min after intraperitoneal administration of
      the drugs showed higher 5-HT2 and lower D2 receptor occupancies of clozapine and
      RMI-81582 than those of haloperidol both in the striatum and frontal cortex. The
      5-HT2/D2 ratios of receptor occupancy for clozapine and RMI-81582 were about 6 to
      8 times higher than that for haloperidol. Stable occupancies of D1 receptors were
      observed only with RMI-81582 and clozapine, the former demonstrating the higher
      occupancy. These findings are in agreement with the previous findings obtained
      under in vitro conditions and may account for some part of the properties of
      atypical antipsychotic drugs.

PMID- 7816869
TI  - Ethopharmacological analysis of rat behavior on the elevated plus-maze.
AB  - Behavioral categories were measured in rats left on an elevated plus-maze for 5
      min, in addition to the traditional measures. Four independent factors emerged
      from a factor analysis. The variables that loaded highly and positively on Factor
      1, seemingly related with anxiety, were: number of entries onto open arms, time
      spent on open arms, percentage of open/total arm entries, percentage of time on
      open arms, scanning over the edge of an open arm, and open arm end-exploring. The
      time spent on enclosed arms loaded highly, but negatively on the same factor.
      Risk-assessment from an enclosed arm also loaded negatively on Factor 1. Number
      of enclosed arm entries, total number of arm entries and rearing loaded highly on
      Factor 2, probably related to motor activity. However, the total number of
      entries also loaded on Factor 1, being thus a mixed index. Similarly, the number
      of open arm entries loaded on both Factors 1 and 2. As expected, the variables
      having high loads on Factor 1 were changed to one direction by administration of
      two anxiolytics (nitrazepam and midazolam) and to the opposite direction by two
      anxiogenic drugs (pentylenetetrazol and FG 7142). Such pattern of drug effects
      was not observed with the remaining variables.

PMID- 7816870
TI  - Lesions of central serotonin systems affect responding on a progressive ratio
      schedule reinforced either by intravenous cocaine or by food.
AB  - The effect of intraventricular infusions of the serotonergic neurotoxin, 5,7
      dihydroxytryptamine (5,7-DHT), was examined in rats trained on a progressive
      ratio schedule for either IV cocaine or food reinforcement. Animals in the 5,7
      DHT treatment group responded to significantly higher breaking points than
      vehicle-injected control animals, regardless of whether food or cocaine was used
      as the reinforcing stimulus. Analysis of the regional brain amines indicated that
      depletions of mesencephalic 5-HT correlated with postsurgical alterations in
      responding. These findings suggest that depletion of forebrain 5-HT produces a
      general effect on responding rather than a specific alteration in the reinforcing
      effects of psychomotor stimulant drugs.

PMID- 7816871
TI  - A deficit in one-trial context fear conditioning is not due to opioid analgesia.
AB  - Rats given a foot shock immediately after placement in a box subsequently freeze
      (immobility) much less in that box than rats given the same shock 2 min after
      placement. A possible explanation of this result is that these two procedures
      might induce different levels of opioid analgesia at the time of shock. Opioids
      might be present immediately after handling, transporting, and exposure to a new
      situation, but absent 2 min later. Two experiments examined this possibility by
      giving the opioid antagonist naloxone before conditioning (Experiment 1) or
      before conditioning and testing (Experiment 2). There was no effect of naloxone
      relative to saline controls. The results do not support the analgesia hypothesis.
      Experiment 2 precludes a stage-dependent learning account of the results.

PMID- 7816872
TI  - Cannabinoids and appetite stimulation.
AB  - Appetite stimulation by cannabinoids is highly variable. Four within-subject
      design studies explored the effects of age, gender, satiety status, route of drug
      administration, and dose on intake. One study involved a single oral
      administration of active drug (15 mg males, 10 mg females) or placebo to an age
      and gender stratified sample of 57 healthy, adult light marijuana users. Eleven
      subjects received single doses by oral, sublingual, and inhaled routes in a
      second study. In the third study, 10 subjects ingested a single oral dose in
      fasted and fed states. A 2.5 mg dose was administered b.i.d. for 3 days by oral
      and rectal suppository routes in the fourth study. Mean daily energy intake was
      significantly elevated following chronic dosing by rectal suppository, but not
      oral capsule, relative to all acute dosing regimens except inhalation. Total
      daily energy intake was comparable on fed and fasted days, suggesting satiety
      mechanisms were not impaired by the drug. Subject age, gender, reported "high,"
      and plasma drug level were not significantly associated with drug effects on food
      intake.

PMID- 7816873
TI  - Evaluation of bradykinesia induction by SM-9018, a novel 5-HT2 and D2 receptor
      antagonist, using the mouse pole test.
AB  - Induction of bradykinesia by SM-9018, a novel 5-HT2 and D2 antagonist, was
      compared with that of other neuroleptics using the pole test in mice.
      Neuroleptics including SM-9018, haloperidol, chlorpromazine, and thioridazine
      dose dependently induced bradykinesia in the pole-descending behavior of mice
      with relative potencies consistent with those for catalepsy induction. SM-9018
      was about 70 times weaker than haloperidol and twice as weak as thioridazine in
      inducing bradykinesia. Other CNS drugs such as barbiturates and antidepressants
      had no effects. Haloperidol-induced bradykinesia was significantly attenuated by
      a cholinergic muscarinic antagonist (i.e., trihexyphenidyl) and 5-HT2 antagonists
      (i.e., ritanserin and cyproheptadine) whereas that caused by SM-9018 was
      relatively resistant to the 5-HT2 antagonists. These findings suggest that SM
      9018 is weaker than other neuroleptics in inducing extrapyramidal side effects
      and that the 5-HT2 blocking activity of SM-9018 may contribute to its atypical
      neuroleptic property.

PMID- 7816874
TI  - Naltrexone, dopamine receptor agonists and antagonists, and food intake in rats:
      1. Food deprivation.
AB  - Different forms of food intake are reduced by both agonists and antagonists of
      dopamine D1 and D2 receptors as well as general opioid antagonists. The present
      study evaluated whether deprivation (24 h)-induced food intake was altered
      following systemic administration of either the D1 agonist, SKF-38393, the D1
      antagonist, SCH-23390, the D2 agonist, quinpirole, or the D2 antagonist,
      haloperidol, alone or in combination with the general opioid antagonist,
      naltrexone. Both SKF-38393 (5-10 mg/kg) and SCH-23390 (100-200 micrograms/kg)
      significantly and dose dependently reduced deprivation-induced intake. Whereas
      quinpirole (0.5-1 mg/kg) failed to alter deprivation-induced intake, haloperidol
      increased deprivation-induced intake at low (50 micrograms) doses and decreased
      intake at higher (100-500 micrograms/kg) doses. Naltrexone (2.5-10 mg/kg)
      significantly inhibited deprivation-induced intake. When naltrexone was paired
      with behaviorally ineffective doses of either SCH-23390 (2.5-100 micrograms/kg),
      quinpirole (0.01-1 mg/kg), or haloperidol (50 micrograms/kg), the degree of
      reduction of deprivation-induced intake was significantly greater than that
      produced by naltrexone alone. Pairing naltrexone with SKF-38393 produced
      reductions of deprivation-induced intake comparable to that of naltrexone alone.

PMID- 7816875
TI  - Naltrexone, dopamine receptor agonists and antagonists, and food intake in rats:
      2. 2-deoxy-D-glucose.
AB  - Significantly greater inhibition of deprivation-induced food intake occurs
      following cotreatment with naltrexone and either the D1 antagonist, SCH-23390,
      the D2 agonist, quinpirole, or the D2 antagonist, haloperidol, relative to
      naltrexone alone. Cotreatment with the D1 agonist, SKF-38393, failed to alter
      naltrexone's inhibition of deprivation-induced intake. The present study
      evaluated whether each of these D1 and D2 agonists and antagonists altered
      hyperphagia following 2-deoxy-D-glucose (2DG) themselves or in combination with
      naltrexone. Neither SKF-38393 (1-10 mg/kg) nor SCH-23390 (25-200 micrograms/kg)
      altered 2DG hyperphagia. Quinpirole (0.025-0.5 mg/kg) dose dependently decreased
      2DG hyperphagia. 2DG hyperphagia was respectively increased and decreased by low
      (50 micrograms/kg) and high (500 micrograms/kg) doses of haloperidol. Cotreatment
      of SKF-38393 (0.1-1 mg/kg) and naltrexone potently enhanced the inhibition of 2DG
      hyperphagia relative to naltrexone alone. In contrast, cotreatment of naltrexone
      and either SCH-23390 (100-200 micrograms/kg) or quinpirole (0.025-0.05 mg/kg)
      inhibited 2DG hyperphagia in a manner similar to that of naltrexone alone.
      Finally, cotreatment of haloperidol (5-50 micrograms/kg) and naltrexone
      transiently enhanced the inhibition of 2DG hyperphagia relative to naltrexone
      alone.

PMID- 7816877
TI  - Responders and nonresponders to cat odor do not differ in other tests of anxiety.
AB  - Laboratory-bred rats can be divided into those showing clear innate behavioral
      responses to the odor of a predator (a cat) and those showing no response.
      However, these two groups did not differ in their responses to a neutral odor, or
      in the social interaction or elevated plus-maze tests of anxiety. This suggests a
      distinction between phobic anxiety (generated by cat odor) and a generalized
      anxiety state (generated by novelty in the other tests). Trial 2 in the plus-maze
      generates a state of fear that is distinct from that generated on trial 1, and
      one suggested to reflect phobic anxiety. Although the groups of cat responders
      and nonresponders did not differ in their scores on trial 2 in the plus-maze, two
      clear groups of responders and nonresponders could be identified on this trial
      (but not on trial 1 or in the social interaction test). This suggests that it is
      possible to identify bimodal populations of rats in tests of both innate and
      acquired simple phobias.

PMID- 7816876
TI  - Paeoniflorin attenuates learning impairment of aged rats in operant brightness
      discrimination task.
AB  - The effects of paeoniflorin isolated from peony were examined on an aging-induced
      learning deficit in an operant brightness discrimination task in Fischer 344
      rats. Learning in aged (25 months) rats was significantly impaired compared with
      young (5 months) rats. Daily administration of paeoniflorin (0.01 mg/kg, PO)
      significantly attenuated the learning impairment in aged rats, whereas it did not
      affect the learning in young rats. Although tacrine (0.3 and 1 mg/kg, IP), a
      cholinesterase inhibitor, also did not affect the learning in young rats, it
      slightly augmented the aging-induced learning deficit in the present task. These
      data indicate the therapeutic potential of paeoniflorin in the treatment of
      senile dementia and aging-induced cognitive dysfunction.

PMID- 7816878
TI  - A three-choice haloperidol-saline-cocaine drug discrimination task in rats.
AB  - This study was conducted to test whether rats could be trained and successfully
      maintain a three-choice drug discrimination task using 0.1 mg/kg haloperidol (SC,
      2-h pretreatment), saline (IP or SC, 2 h and 15 min pretreatment), and 10 mg/kg
      cocaine (IP, 15-min pretreatment) as training stimuli. Six male Sprague-Dawley
      rats achieved criterion performance for stimulus control by these training
      stimuli under a fixed-ratio-5 schedule of food reinforced lever-press responding
      in an average of 164 training sessions. Dose-response functions for cocaine and
      haloperidol demonstrated both quantitative and qualitative specificity of the
      training stimuli. The data also are presented along a single pharmacological
      continuum (agonist-antagonist) that we hypothesize to represent a parallel
      subjective or interoceptive stimulus continuum associated with the drug
      injections. Based on the previous multidimensional model of drug stimuli
      dimensionality (3), this specific stimulus dimension is characterized as an
      unidimensional bipolar continuum represented by the hypothetical states of
      hedonia or euphoria on one end (cocaine) and anhedonia or depression on the
      opponent end (haloperidol), with a neutral (saline) centroid region. We propose
      that this specific three-choice drug discrimination task in rats may function as
      an animal analog of the subjective states associated with cocaine abuse and the
      subsequent withdrawal or, crash, in humans (7,8,21).

PMID- 7816879
TI  - The effects of acute cocaine administration on the DOI-induced head-twitch
      response in reserpinized mice.
AB  - Previously it was shown that acute cocaine administration dose dependently
      reduces the 5-HT2-receptor-mediated DOI [(+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2
      aminopropane]-induced head-twitch response (HTR) in mice via indirect stimulation
      of the inhibitory adrenergic alpha 2- and serotonergic 5-HT1A receptors. In
      addition, the inhibitory capacity of cocaine was enhanced fourfold in mice with 5
      HT2-receptor supersensitivity induced by a single injection of DOI 48 h prior to
      experimentation. The aim of the present investigation was to determine the
      inhibitory capacity of cocaine in reserpinized mice. A single injection of
      reserpine 48 h prior to DOI administration caused supersensitivity in the DOI
      induced HTR. Two reserpine injections did not further enhance this
      supersensitivity effect. Once reserpinized 5-HT2-receptor supersensitive animals
      were less responsive to the inhibitory effects of cocaine on the DOI-induced
      behavior than were the mice, as reported previously, that were made
      supersensitive by DOI pretreatment. The inhibitory capacity of cocaine was
      further attenuated when mice were reserpinized twice prior to determination of
      its effects on the DOI-induced behavior. Taken together with previously published
      data, the present investigation lends further support for the importance of
      endogenous levels of 5-HT and norepinephrine on the ability of cocaine to
      attenuate the DOI-induced HTR.

PMID- 7816880
TI  - The use of a biopsy punch in surgical preparation of drug self-administering
      animals.
AB  - This report describes a simple surgical method of exiting an implanted
      intravenous catheter through the skin via a nonsutured site. The preparation,
      which makes use of a biopsy punch, avoids placing the catheter exiting point
      through the incision used for subcutaneously fixing the catheter platform on the
      back of the animal.

PMID- 7816881
TI  - Influence of cholinesterase inhibitors on cortical slow-wave activity in aging
      nonhuman primate.
AB  - Substantial evidence has now accumulated suggesting that the cognitive decrements
      characteristic of Alzheimer's disease and, to a lesser degree, of normal aging,
      may result, at least in part, from degenerative changes in the cholinergic system
      innervating archi- and neocortices. This evidence for cholinergic degeneration in
      AD has provided the key rationale for many recent clinical trials utilizing
      cholinergic agents for the purpose of palliating cognitive loss. The basal
      forebrain cholinergic system plays an important function in electrocortical
      activation associated with behavioral arousal and cognitive functions. We
      recorded electrocortical changes from nonhuman primates following administration
      of potentially clinically useful cholinergic agonists as well as an antagonist.
      The cholinesterase inhibitors tacrine (THA) and, to a lesser extent,
      physostigmine (PHYSO) and amodiaquine (AMDQ), caused an upward shift in the
      frequency of the resting electrocortical activity, although scopolamine
      significantly slowed the activity below baseline levels. We believe these
      findings support the concept that the cholinergic system may play an important
      role in cognitive processes associated with cortical activation.

PMID- 7816882
TI  - Dissociation of buprenorphine-induced locomotor sensitization and conditioned
      place preference in rats.
AB  - The locomotor and rewarding effects of the opioid mixed agonist-antagonist
      buprenorphine were assessed in a conditioned place preference (CPP) experiment.
      Separate groups of rats were given one of three doses of buprenorphine (0.3, 1.0
      or 3.0 mg/kg) or saline paired with the white compartment of a CPP apparatus. The
      following day, all rats received saline paired with the black compartment. After
      six conditioning trials, rats were given free access to all compartments of the
      CPP apparatus. Horizontal activity data obtained during conditioning revealed
      increased activity (i.e., behavioral sensitization) for the three doses on trial
      6. Vertical activity data revealed significant increases on trial 6 for the 1.0
      and 3.0 mg/kg doses only. Significant CPP was obtained with the 0.3 mg/kg and 1.0
      mg/kg doses of buprenorphine, but not with the 3.0 mg/kg dose. These data
      indicate that buprenorphine elicits locomotor sensitization after repeated
      exposures that follows a linear dose-response relationship. In contrast, these
      data suggest that the rewarding effects of buprenorphine follow an inverted U
      shaped dose-response curve.

PMID- 7816883
TI  - Enhanced locomotor reactivity to apomorphine following repeated cocaine
      treatment.
AB  - To study the involvement of postsynaptic dopamine (DA) receptors in cocaine
      induced behavioral sensitization, locomotor responses to apomorphine (APO, 360
      micrograms/kg, IP), a direct DA agonist, were compared in rats repeatedly treated
      with cocaine (15 mg/kg, IP x 5 and one challenge injection 4 days later) and
      saline under different environmental conditions. When cocaine was injected under
      activated conditions, immediately before animal placement in activity chamber,
      more powerful locomotor response to the initial drug and a significant effect of
      repeated treatment (sensitization) were found compared to drug administration
      under quiet conditions, 2 h after animal placement in activity chamber. In this
      case, locomotor response to the initial drug was similar to that of saline, and
      the effect of repeated injections on locomotion was absent (no sensitization).
      Locomotor stimulation induced by APO was significantly enhanced in both groups of
      cocaine-treated animals compared to saline controls. This effect, however, was
      more powerful in animals treated with cocaine under activated conditions. Present
      data suggest that enhanced responsiveness of postsynaptic DA receptors developed
      due to chronic cocaine treatment may contribute to stable alteration of DA
      transmission thought to mediate cocaine sensitization.

PMID- 7816884
TI  - Nucleus accumbens dopamine release increases during instrumental lever pressing
      for food but not free food consumption.
AB  - This experiment was undertaken to investigate the role of nucleus accumbens
      dopamine (DA) in instrumental and consummatory responses for food. In vivo
      microdialysis methods were used to study DA release and metabolism in the nucleus
      accumbens of behaving rats. Four behavioral conditions were used: performance on
      a fixed ratio 5 (FR 5) schedule of food reinforcement, consumption of Bioserve
      food pellets, consumption of laboratory chow, and food deprivation control.
      Groups of rats that were previously exposed to these conditions were implanted
      with dialysis probes in the nucleus accumbens and tested the day after
      implantation. The rats that pressed a lever on a FR 5 schedule showed significant
      increases in extracellular DA and DA metabolites compared to food-deprived
      control rats. In further analyses, rats that responded on the FR5 schedule were
      divided into three groups based upon their response rates. The rats with low
      response rates did not significantly differ from control rats, whereas rats with
      medium and high rates of responding showed significant increases in DA release
      relative to the control group. Rats that received massed presentation of food
      pellets or laboratory chow consumed large quantities of food, but showed no
      significant increases in DA release. This experiment demonstrated that
      performance of lever pressing behavior is accompanied by an increase in accumbens
      DA release and metabolism, and that DA release in nucleus accumbens is more
      closely related to the performance of highly active instrumental responses than
      it is to consumption of large quantities of food.

PMID- 7816885
TI  - Different location of benzodiazepine sites involved in gut and behavioral effects
      of benzodiazepine withdrawal in rats.
AB  - This work was performed to determine if the alterations in gastric emptying
      induced by precipitated withdrawal are linked to peripherally or centrally
      located benzodiazepine sites, in rats treated chronically with diazepam (15
      mg/kg/day IP) for 7 days. In sham-capsaicin-treated rats, precipitated withdrawal
      by flumazenil (15 mg/kg IP) induced an increase of gastric emptying, whereas it
      had no effect in systemic capsaicin-treated rats. Both groups of animals
      developed withdrawal syndrome expressed as motor, autonomic, and behavioral
      signs. On diazepam-dependent rats, central administration of flumazenil (0.15
      mg/kg ICV) induced withdrawal syndrome but had no effect on gastric emptying.
      These preliminary results suggest that benzodiazepine receptors located in the
      central nervous system are involved in behavioral withdrawal syndrome, whereas
      benzodiazepine receptors located at the peripheral level are responsible for
      digestive withdrawal syndrome involving capsaicin-sensitive neurons.

PMID- 7816886
TI  - Cholesterol treatment facilitates spatial learning performance in DBA/2Ibg mice.
AB  - DBA/2Ibg mice were treated with cholesterol pellets for 11 days. On the seventh
      day after treatment, animals began 5 consecutive days of training on the spatial
      form of Morris water task, followed on the third and fourth days by a probe
      trial, and random platform training on the fifth day. DBA mice with cholesterol
      pellets exhibited enhanced performance compared to DBA mice that underwent a sham
      surgery. Our results suggest that subchronic treatment with the steroid hormone
      precursor, cholesterol, enhances spatial learning performance in DBA mice.

PMID- 7816888
TI  - Behavioral assessment of high-dose amphetamine withdrawal: importance of training
      and testing conditions.
AB  - Chronic d-amphetamine-treated rats were given twice daily injections at a dose of
      7.5 mg/kg for 2 weeks. Acute amphetamine and saline groups of rats were given
      saline treatments during this time, except that for the acute group the final
      injection was 7.5 mg/kg d-amphetamine. Acute and chronic amphetamine groups
      habituated to the locomotor activity testing apparatus showed increases in both
      distance traveled and repetitive movement time that lasted up to 6 h following
      the final injection. When animals were not habituated to the activity test
      apparatus, however, a significant decrease in repetitive movement time was noted
      for the chronic amphetamine group 24-54 h following the final amphetamine
      injection; no differences were observed for distance traveled when the locomotor
      activity apparatus was novel. Swim test immobility time was assessed twice
      following the last injection, with the second test following the first by
      approximately 24 h. During the first test, decreases in immobility were observed
      for both chronic and acute amphetamine groups, 6-12 h following the last
      injection. However, during the second test, decreases in immobility time were
      observed only for the chronic amphetamine groups 36-72 h following the final
      injection. These results indicate that 24 to 72 h after the end of the chronic
      amphetamine regimen a withdrawal effect was observed for both repetitive movement
      time in the locomotor activity test and immobility time in the swim test. The
      withdrawal effect was observed only for the locomotor activity groups for whom
      the test apparatus was novel, and only during the second test of immobility time
      for the swim test groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7816887
TI  - Effects of bilateral cholinotoxin infusions on the behavior and brain
      biochemistry of the rats.
AB  - We examined behavioral and biochemical specificity and the general usefulness of
      the proposed rat model of Alzheimer's disease. Bilateral infusions of
      ethylcholine aziridinium (AF64A) into the basal magnocellular nuclei caused a
      deterioration of learning in passive and active avoidance tests, increased
      emotional reactivity, and decreased motoric activity. Choline acetyltransferase
      activity was decreased by 22% in the frontal cortex but increased by 8-10% in the
      hippocampus and hypothalamus. Noradrenaline and dopamine levels in the frontal
      cortex were decreased by 20%. In striatum, dopamine and its metabolites were
      strongly suppressed (by 50-60%). Also striatal noradrenaline (-48%) and 5
      hydroxytryptamine (-34%) were significantly decreased. Hypothalamic 5
      hydroxytryptamine was increased (+25%). Bilateral AF64A lesions decreased
      significantly (by 14-20%) activities of prolyl endopeptidase, dipeptidyl
      peptidase II and IV in hippocampal and frontal cortical brain homogenates. These
      results show that AF64A can be used to induce long-term learning deficits in the
      rat. However, striatal amine levels are also strongly suppressed, and are
      reflected as hypomotility and increased emotional reactivity. These changes may
      limit the usefulness of the rat model. Universally decreased peptidase activities
      offer interesting views regarding the role of peptidase inhibitors in amnestic
      disorders.

PMID- 7816889
TI  - Evidence for central benzodiazepine receptor heterogeneity from behavior tests.
AB  - To explore behavioral selectivity as a consequence of multiple receptor subtypes,
      four benzodiazepine receptor ligands, flunitrazepam, CGS 9896, zolpidem, and AHR
      11797, were tested at five in vivo endpoints: anticonvulsant action,
      anxiolysis/anxiogenesis as determined in the plus-maze test, locomotor activity,
      changes in food consumption, and hypothermia. All compounds produced hypothermia.
      In the plus-maze test, flunitrazepam, CGS 9896, and a low dose of zolpidem (0.05
      mg/kg) increased the time spent in the open arms, although AHR 11797 and higher
      doses of zolpidem decreased time spent in the open arms. Flunitrazepam and
      zolpidem greatly reduced, CGS 9896 slightly reduced, and AHR 11797 did not affect
      locomotor activity. Flunitrazepam and CGS 9896 increased food consumption, but
      AHR 11797 and zolpidem had no effect. Only flunitrazepam fully protected the
      animals from pentylenetetrazol-induced seizures. The qualitative differences in
      the effects of these compounds observed are difficult to explain by activation of
      a single benzodiazepine receptor subtype. As Ro15-1788 antagonized all the
      observed effects, these compounds act through multiple central benzodiazepine
      receptors.

PMID- 7816890
TI  - Norepinephrine and serotonin alterations following chronic stressor exposure:
      mouse strain differences.
AB  - Exposure to acute uncontrollable foot shock influenced the levels and utilization
      of norepinephrine (NE) and serotonin (5-HT) in several brain regions. These
      effects varied between the BALB/cByJ and C57BL/6J mouse strains, with the former
      displaying more pronounced amine variations. Following repeated exposure to foot
      shock over 15 days, the decline of NE associated with an acute stressor was
      abrogated. In the hypothalamus, this was accompanied by high MHPG accumulation,
      suggesting that the increased NE stemmed from a compensatory increase in
      synthesis. In the locus coeruleus and prefrontal cortex the accumulation of MHPG
      declined with repeated exposure, possibly suggesting moderation in utilization.
      In animals exposed to a chronic unpredictable stressor regimen, the NE decline in
      the hypothalamus was precluded, but pronounced NE reductions were still evident
      in the locus coeruleus and prefrontal cortex. The data are related to behavioral
      impairments associated with stressor application, as well as to the particular
      vulnerability of BALB/cByJ mice to stressor-induced behavioral impairments.

PMID- 7816891
TI  - Nicotine self-administration and locomotor activity are not modified by the 5-HT3
      antagonists ICS 205-930 and MDL 72222.
AB  - The subtype-selective serotonin 5-HT3 antagonists MDL 72222 and ICS 205-930 were
      tested for their ability to modify nicotine self-administration and locomotor
      activity in rats. In self-administration experiments, MDL 72222 produced no
      statistically significant changes over a dose range of 1 to 30 micrograms/kg, nor
      at the considerably higher dose of 1 mg/kg. MDL 72222 was similarly without
      effect in nicotine-produced locomotor activity, except at the 1 mg/kg dose, which
      reduced scores. In an initial test on nicotine self-administration, ICS 205-930
      produced a small decrease in drug-taking behavior at 1 and 3 micrograms/kg which
      just reached statistical significance, but had no effects at higher doses.
      However, these low-dose effects could not be replicated. In addition, ICS 205-930
      was without effect on nicotine locomotor activity, even at the two low doses that
      had reduced self-administration. We conclude that these 5-HT3 antagonists do not
      modulate nicotine reinforcement or behavioral arousal.

PMID- 7816892
TI  - Regional serotonin1A receptors in the CNS of alcohol-preferring and 
      nonpreferring rats.
AB  - The densities of serotonin1A (5-HT1A) receptors, labeled with [3H]8-hydroxy-2-(di
      n-propylamino) tetralin (8-OH-DPAT), were examined in the CNS of alcohol-naive
      adult male alcohol-preferring (P) and -nonpreferring (NP) rats using quantitative
      autoradiography. The densities of sites labeled with 2 nM [3H]8-OH-DPAT were a)
      20-30% higher in the medial prefrontal, frontal (layers 1, 2, and layers 3-6),
      parietal (layers 3-6), and cingulate cortex; b) 35-40% higher in the
      retrosplenial, occipital (all layers), temporal (all layers) cortex; and c) 15%
      higher in the entorhinal cortex of the P compared with the NP rat. Within the
      hippocampus, significant differences between the rat lines were observed only in
      the posterior portion where the densities of [3H]8-OH-DPAT labeled sites were a)
      10-15% higher in the dorsal dentate gyrus, dorsal CA1, and dorsal CA3 regions;
      and b) 15-25% higher in the anterior ventral hippocampal area and ventral dentate
      gyrus of the P relative to the NP line. In contrast to the above results, the
      densities of [3H]8-OH-DPAT labeled sites were 15-20% lower in the dorsal,
      paradorsal, and median raphe nuclei of the P compared with the NP rat. No
      differences in [3H]8-OH-DPAT binding between the rat lines were found in several
      basal ganglia, limbic, and brain stem regions. The data indicate that there are
      greater numbers of postsynaptic 5-HT1A receptors in certain parts of the cerebral
      cortex and hippocampus of the P compared with the NP rat.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7816893
TI  - Separate and combined effects of dopamine D1 and D2 receptor agonists on key
      pecking in the developing chick.
AB  - The separate and combined effects of dopamine D1 and D2 agonists on key-peck
      responding of young chicks for heat reinforcement were determined. In the first
      experiment, 1- and 4-day-old chicks (n = 96) were injected SC with either
      distilled water or 5 mg/kg reserpine 18 h before testing. Twenty minutes before a
      24-trial autoshaping session, chicks were injected IP with either distilled water
      or 10 mg/kg SKF 38393 and 2 mg/kg quinpirole. Chicks receiving both dopamine
      agonists had enhanced key-peck responding in both pretreatment conditions. In
      Experiment 2, 1- and 4-day-old chicks (n = 192) of two strains received 5 mg/kg
      reserpine SC 18 h before testing. Twenty minutes before their autoshaping session
      these chicks were injected IP with either distilled water, 10 mg/kg SKF 38393, 2
      mg/kg quinpirole, or 10 mg/kg SKF 38393 and 2 mg/kg quinpirole. After reserpine
      pretreatment, chicks of both strains responded on more trials when given both
      dopamine agonists compared with controls given either distilled water or single
      agonist treatment. No age or strain differences in key pecking were produced by
      the combined administration of these dopamine agonists. Therefore, functional
      coupling of the dopamine D1 and D2 receptors is found within 1 day after hatching
      in the domestic chick.

PMID- 7816894
TI  - Monoamine depletion attenuates the REM sleep deprivation-induced increase in
      clonidine response in the forced swimming test.
AB  - Effect of monoamine depletion on the REM sleep (REMs) deprivation-induced
      increase in clonidine response in the forced swimming test was investigated. Mice
      were deprived of REMs by the small pedestal method. Clonidine HCl (10-1000
      micrograms/kg, IP), an alpha 2-adrenoceptor agonist, dose dependently increased
      swimming activities in group-housed and socially isolated mice used as the
      control groups. The dose-response relationship shifted to the left following REMs
      deprivation (ED50 values in the group-housed, isolated, and REMs-deprived mice
      were 250, 200, and 27 micrograms/kg, respectively). Monoamine depletion, induced
      by reserpine (5 mg/kg, IP) plus alpha-methyl-p-tyrosine (250 mg/kg, IP), did not
      produce any changes in the effects of clonidine in the control groups. However,
      in REMs-deprived mice, monoamine depletion significantly decreased the effect of
      100 micrograms/kg clonidine, but not that of 300 micrograms/kg clonidine on
      swimming activity. These results indicate that clonidine-induced increase in
      swimming activity in the forced swimming test is mainly mediated by postsynaptic
      alpha 2-adrenoceptor, and that endogenous noradrenaline in the brain plays an
      important role in the increase of clonidine response following REMs deprivation
      treatment. The neuronal mechanism of the increase in clonidine response is
      discussed.

PMID- 7816895
TI  - Nucleus accumbens dopamine depletions in rats affect relative response allocation
      in a novel cost/benefit procedure.
AB  - Rats were tested on days 1, 3, and 5 of a 5-day test week in an operant chamber
      in which they could either lever press on a fixed-ratio 5 (FR5) schedule to
      obtain food pellets (Bioserve) or approach and consume lab chow that was also
      available in the chamber (Teklad Premier). Rats typically pressed at high rates
      to obtain the food pellets and ate little of the lab chow. On days 2 and 4 of
      each week lab chow was not concurrently available, and rats could only lever
      press on the FR5 schedule for pellets to obtain food. Dopamine depletions
      produced by intraaccumbens injections of the neurotoxic agent 6-hydroxydopamine
      produced a dramatic decrease in lever pressing and increase in chow consumption
      on days when lab chow was available. Lever pressing was not significantly reduced
      in dopamine-depleted rats on days when chow was not available, although there was
      a significant correlation between lever pressing and accumbens dopamine levels.
      These results suggest that nucleus accumbens dopamine depletions do not produce a
      general deficit in food motivation. Moreover, accumbens dopamine depletions do
      not appear to produce severe deficits in fine motor control that impair the
      execution of individual motor acts involved in lever pressing. Rather, the
      present results are consistent with the notion that accumbens dopamine sets
      constraints upon which food-related response is selected in a particular
      situation, and that these depletions alter the relative allocation of food
      related responses.

PMID- 7816898
TI  - The 5-amino-3-methyl-4-ureidoisoxazoles, synthesis and antileucemic activity.
AB  - Some new substituted 5-amino-3-methyl-4-ureidoisoxazoles and the 4-ethyl urethane
      of the 5-amino-3-methyl-isoxazole have been synthesized from 5-amino-3-methyl-4
      isoxazolecarboxylic acid azide. Some representative ureides with primary,
      secondary, and heterocyclic amines were tested for their antileucemic activity.

PMID- 7816896
TI  - Central administration of two 5-HT receptor agonists: effect on REM sleep
      initiation and PGO waves.
AB  - Cholinergic neurons in the pedunculopontine tegmental (PPT) and the laterodorsal
      tegmental (LDT) nuclei are implicated in the generation of rapid eye movement
      sleep (REM) and ponto-geniculo-occipital (PGO) waves. Serotonin (5-HT) has a role
      in sleep-wake regulation and appears to inhibit PGO wave generation. We studied
      the effects of the central infusion of the relatively specific 5-HT1A receptor
      agonist 8-hydroxy-2-(n-dipropylamino)tetralin (DPAT) and the less specific 5-HT1
      receptor agonist 1(3-chlorophenyl)piperazine (mCPP) on the regulation of REM and
      on PGO wave generation. DPAT (0.0, 0.002, 0.01, 0.08, and 0.8 microgram/0.5
      microliter normal saline) and mCPP (0.0, 0.02, 0.2, 2.0, and 20.0 micrograms/0.5
      microliter normal saline) were infused unilaterally into the peribrachial region
      of PPT (PB) in cats. Additionally, DPAT (0.01 microgram/0.5 microliter) was
      infused bilaterally into PB in a separate experiment. Low dosages of DPAT
      (unilateral or bilateral) decreased successful entrances into REM (0.01
      microgram) and time spent asleep (0.002 microgram and 0.01 microgram) without
      affecting outward behavior. No dosage of mCPP significantly decreased the number
      of REM episodes, and neither drug decreased REM episode duration once REM had
      been entered. Neither drug affected the rate of PGO waves independently of
      modulating behavioral state. We propose that 5-HT1A receptor mechanisms have an
      inhibitory role in actual REM initiation, possibly by facilitating endogenously
      generated excitation of brainstem startle mechanisms at the onset of REM.

PMID- 7816897
TI  - Muscarinic receptors: focus on presynaptic mechanisms and recently developed
      novel agonists and antagonists.

PMID- 7816899
TI  - Synthesis of some new 1,6-dihydro-3-substituted 6-spiro-(9'-fluorene)-1,2,4
      triazin-5-(4H)-ones as potential anti HIV and anticancer drugs.
AB  - 1,6-Dihydro-3(2H)-thioxo-6-spiro-(9'-fluorene)-1,2,4-triazin -5(4H)-one (1) has
      been used to synthesize several analogous compounds via nucleophilic substitution
      reactions. Spectroscopic data are given in support of the proposed structures.
      Some of the new products possessed good anti HIV and anticancer activities.

PMID- 7816900
TI  - [HPLC-determination of loratadine and its active metabolite
      descarboethoxyloratadine in human plasma].
AB  - The quantitative determination of loratadine (1) and its active metabolite
      descarboethoxyloratadine (2) is described. Because of the high difference in
      polarity between 1 and 2, the two analytes were determined in two HPLC-systems
      separately. As internal standards propyl-4-(8-chloro-5,6-dihydro-11H-benzo-[5,6]
      cyclohepta-[1,2-b]- pyridin-11-ylidin)-1-piperidincarboxylate (3) and 1-ethyl-4
      (8-chloro-5,6-dihydro-11H-benzo-[5,6]-cyclohepta- [1,2-b]-pyridine-11-ylidin)
      piperidine (4) were used for 1 and 2, respectively. After extraction with organic
      solvents from 1 ml plasma, 1 and 2 were reextracted with diluted phosphoric acid
      from the organic phase. Chromatographic separation on a RP-18 column and
      fluorescence detection allowed a sufficiently sensitive determination of 1 and 2
      in plasma with a lower limit of quantitation of 0.5 ng/ml for both analyts. The
      method was successfully applied to human plasma samples from 16 subjects after
      oral administration of 20 mg 1.

PMID- 7816901
TI  - Anti-Candida activity of synthetic hydroxychalcones.
AB  - The antifungal activity of different synthetic hydroxychalcones was determined
      against Candida species. It was revealed that the presence of hydroxyl groups at
      C-2, C-4, and C-2' in chalcone was essential to inhibit Candida growth. Among the
      chalcone derivatives examined, 2,4,2'-trihydroxy-5'-methylchalcone showed the
      most intensive anti-Candida activity, suggesting that it could be a potential
      therapeutic agent for candidosis.

PMID- 7816902
TI  - A simple cytotoxicity assay using the eucaryotic microorganism Dictyostelium
      discoideum.
AB  - First attempts to evaluate the potential of the cellular slime mold Dictyostelium
      discoideum as a model system for cytotoxic tests of potential drugs are
      described. Using the cell counter and analyser system, CASY 1, two parameters,
      cell count and mean cell volume, could be established as relevant parameters to
      estimate cytotoxicity. The effects on these two parameters of two well
      characterized drugs, the gentamycin analogue G418 and doxorubicin, are reported.

PMID- 7816903
TI  - New verapamil related N-homoveratryl propionamides which sensitize tumor cells.

PMID- 7816904
TI  - Determination of verapamil and its metabolites in plasma using HPLC.

PMID- 7816905
TI  - Structure-activity relationship studies of CNS agents. Part 16: A lower limit of
      a distance between crucial pharmacophores of 5-HT1A ligands.

PMID- 7816906
TI  - Cardioselectivity of some beta-blockers related to acebutolol.

PMID- 7816907
TI  - Pharmacokinetics of calcitonin and osteocalcin marked 125J in rats.

PMID- 7816908
TI  - Effect of Kampo medicines on alloxan-induced diabetes in mice.

PMID- 7816909
TI  - The origin of vertebrates and the principle of succession of functions.
      Genealogical sketches by Anton Dohrn 1875. An English translation from the
      German.

PMID- 7816910
TI  - Emergence of new fields in ecology: the case of life history studies.
AB  - We examine the emergence of the field of life-history strategies during the
      1950s. (We consider a 'field' an area of scientific activity consisting of a
      theoretical core, a subject of research, a vocabulary and research tools). During
      the late 1940s and early 1950s, population ecology faced many problems,
      concerning its conceptual framework, its mathematical models, experimental
      deficiencies, etc. Research on life-history characteristics remained descriptive,
      lacking explanations about the causes and significance of phenomena. This was due
      to the deficiencies of the theoretical framework of population ecology up to the
      1950s. The catalyzing factor for the emergence of the new field was the
      interdisciplinary impacts, and especially the impact of neodarwinism. The
      elaboration of a new theoretical core, invoking also methodological shifts, was
      the triggering factor, conditioning the emergence of the new field.

PMID- 7816911
TI  - [Differential diagnosis of lung metastases].

PMID- 7816912
TI  - [Surgical therapy of lung metastases. An interdisciplinary responsibility].
AB  - Surgical therapy of lung metastases is now an established procedure. The
      operation's purpose is radical, and therefore potentially curative, resection.
      There are also diagnostic and palliative indications. Median sternotomy is the
      standard approach as it allows revision of both lungs, which is important even
      when disease seems to be unilateral. Preoperative staging does not give a
      reliable idea of the number and extent of metastases. From 1972 to 1991, a total
      of 843 operations for lung metastases were carried out in 729 patients in the
      surgical department of the Thorax Clinic in Heidelberg (Rohrbach). The 30-day
      mortality was 2.9%, and the overall 5-year survival from the date of resection of
      the metastases was 33%. The best results were achieved in testicular cancer, with
      a 5-year-survival rate of 67%, and the poorest were observed in melanomas, with
      only 12% 3-year survival. In addition to the primary tumour, and in some cases
      depending on it, several other prognostic factors were relevant: radicality,
      sarcoma vs. carcinoma (carcinoma involved a better prognosis), disease-free
      interval, type of resection, thoracic lymph node involvement. Multivariate
      analysis showed that the prognostic influence of the factors varies considerably
      with the kind of primary tumour. Surgical treatment of lung metastases is part of
      an interdisciplinary oncological therapeutic concept offering prolongation of
      survival to most of the patients concerned and even the possibility of cure to
      some. Even if prolongation of survival is not feasible, an improved quality of
      life and therefore good palliation are obtained.

PMID- 7816913
TI  - [Computerized tomography in diagnosis of lung metastases: improvement with the
      spiral technique].
AB  - Computed tomography is the imaging modality of choice for detection or exclusion
      of pulmonary metastases. In most cases these are spheric, multiple, bilateral,
      and located in the peripheral areas of the middle and lower fields of the lungs.
      Differential diagnosis of solitary pulmonary nodules is difficult. Evaluating
      whether they are malignant or benign is insufficient despite the application of
      multiple CT criteria. Spiral computed tomography acquiring an imaging volume in a
      breathhold has led to significant improvement in the sensitivity of detecting
      pulmonary nodules. Imaging protocols are presented, and the influence of the
      different parameters is discussed. Although not all pulmonary metastases may be
      detected with spiral computed tomography, it is the most important examination
      when considering pulmonary metastasectomy. Computed tomography is the imaging
      modality of choice when monitoring pulmonary metastases during systemic
      therapeutic regimens by measuring all nodules or "indicator lesions."

PMID- 7816914
TI  - [Fine needle punch biopsy of the lung. Results and complications].
AB  - The diagnostic accuracy and complication rate of computer tomography (CT)-guided
      small-caliber cutting needle biopsy were assessed in 103 biopsies in 101
      consecutive patients. There were 67 true-positive, 30 true-negative, 3 false
      negative and no false positive results. Two specimens were unclassifiable and one
      was insufficient. Diagnostic accuracy was 94.1%, sensitivity 95.7%, and
      specificity 100%. In 34% of cases pneumothorax occurred, requiring therapy in 24%
      of cases. The longer the intrapulmonary biopsy route was, the greater the risk of
      pneumothorax. Except for transient hemoptysis in two patients, there were no
      further complications. CT-guided small-caliber cutting needle biopsy of the lung
      is an effective and safe procedure, comparing well with fine needle aspiration
      biopsy (FNAB). If exact histologic diagnosis is required it should be preferred
      to FNAB.

PMID- 7816915
TI  - [MR tomography of lung metastases with rapid gradient echo sequences. Initial
      results in diagnostic applications].
AB  - Rapid gradient echo sequences enable MR imaging (MRI) of pulmonary metastases
      with acquisition times of less than 1 s per slice. By optimization of this
      technique, density, T1- and T2-weighted images can be obtained (FLASH: TR 6.5 ms,
      TE2 = 3 ms, alpha = 10 degrees; T1w-Turbo-FLASH: TI 200 ms, TR 6.5 ms, TE2 = 3
      ms, alpha = 10 degrees; T2w-Turbo-FLASH: TE1 = 50 ms, TR = 6.5 ms, TE2 = 3.5 ms;
      alpha = 10 degrees). In a prospective study 25 patients in whom pulmonary
      metastases were suspected were examined with three techniques in all three
      anatomical planes prior to surgery. All lung metastases revealed a high signal
      intensity on the FLASH as well as the T2w-Turbo-FLASH images, whereas vascular
      structures revealed a low signal intensity on the T2-weighted Turbo-FLASH images.
      Analysis regarding detection and correct number of lung metastases per patient
      with MRI compared with the histology revealed (n = 25): sensitivity of 82%,
      specificity 67%, positive predictive value of 95% and negative predictive value
      of 33%. While MRI does not currently have any diagnostic advantages over CT, the
      excellent differentiation of parenchymal lesions and vascular structures without
      the use of contrast medium and the variability of imaging planes are significant
      methodological advantages.

PMID- 7816916
TI  - [Evaluation of pulmonary lesions with positron emission tomography].
AB  - Positron emission tomography (PET) with fluor-18-labeled deoxyglucose (FDG)
      enables metabolically oriented imaging of intrapulmonary lesions. PET is
      currently not used for the detection of lung metastases, but for further
      diagnostic differentiation of nodules that have already been detected. The
      diagnostic accuracy of FDG-PET is currently dependent on the size of the
      metastatic lesions and the uptake intensity. Significantly increased FDG uptake
      is strongly suggestive of malignant disease whatever the size of lesion
      concerned. Differentiation of a solitary metastasis from a primary lung tumor is
      not possible. Slightly elevated FDG uptake can also be found in tuberculosis,
      sarcoidosis and other granulomatous or inflammatory processes. Exclusion of
      metastatic disease with PET is currently only reliably possible for lesions
      larger than 2.0 cm in diameter, owing to respiratory motion and effects of
      partial volume.

PMID- 7816917
TI  - [Diagnosis of metastases in thoracic images. Progress by further development of
      the conventional film-foil technique?].
AB  - In addition to digital radiography and AMBER, the development of asymmetric
      screen-film systems is another attempt to optimize chest radiography. Due to
      reduced contrast in the parenchyma, the former asymmetric screen-film systems did
      not show sufficient image quality. Three new asymmetric systems with completely
      different composition are available now. In-Sight VHC (Kodak), High Light GUV
      (3M) and Opthos D (Agfa) were compared to standard chest films using
      densitometric curves, a chest phantom for high and low contrast detectability, a
      nodule detection phantom and patient studies. The sensitivity of nodule detection
      in the mediastinum has been 41-48% for L-films and 58-65% for the asymmetric
      screen-film systems. No differences could be demonstrated for nodule detection in
      the lung field. Contrast in the parenchyma is equivalent to L-films. There is no
      loss of diagnostic information in the lung field. Differences between the
      asymmetric systems concern speed, dynamic range and granularity. If AMBER and
      digital radiography are not available, new asymmetric screen-film systems can
      improve nodule detection without further investment costs.

PMID- 7816918
TI  - [Color Doppler ultrasound of the mediastinum. Examination technique and sectional
      anatomy of the image].
AB  - The standardized technique and typical normal findings of color-coded duplex
      sonography of the mediastinum are described. Anatomical structures of the
      sonographical presentations are explained. Important mediastinal regions, vessels
      and lymph nodes can be assessed sonographically. The conventional B-mode
      technique provides topographical orientation and is suitable for high-resolution
      imaging of mediastinal structures. The color-coded display of blood flow allows
      reliable identification of the various mediastinal vessels. The qualitative and
      quantitative characterization of blood flow (flow direction, flow velocity, flow
      quality: arterial-venous, laminar, turbulent) provides additional noninvasive
      information about the hemodynamics of the mediastinal vascular system.

PMID- 7816920
TI  - [Diagnosis of poly-orchidism].
AB  - In a patient referred for sclerotherapy of a varicocele, three testicles and
      focal atrophy in one testicle were additionally diagnosed by ultrasound and MR.
      In the literature other diseases are occasionally described accompanying this
      rare benign congenital anomaly.

PMID- 7816919
TI  - [Transthoracic punch biopsy of mediastinal tumors].
AB  - 48 consecutive patients underwent biopsy of anterior mediastinal tumors under
      sonographic guidance by the use of cutting needles up to 2.0 mm in diameter. The
      results of needle biopsies were compared with the final diagnoses, which was
      proved with pathologic studies or clinicoradiologic follow-up. In 39 (93%) of 42
      malignant tumors malignancy could be readily diagnosed. Examinations of the
      microcylinders of tissue resulted in correct histologic diagnoses in 32 (76%) of
      42 malignant tumors including 13 (81%) of 16 Hodgkin's lymphomas, 6 (66%) of 9
      non-Hodgkin lymphomas, 2 (66%) of 3 thymomas and 9 (82%) of 11 carcinomas. All 6
      benign lesions were correctly identified. No complications such as hemorrhage or
      pneumothorax were encountered.

PMID- 7816921
TI  - [Pain in the left iliosacral region. Plasmacytoma of the ilium].

PMID- 7816922
TI  - [Flank pain, weight loss and leukocytosis. Panarteritis nodosa].

PMID- 7816923
TI  - Can physicians testify as to "nursing negligence"?

PMID- 7816924
TI  - Vicarious liability for nurses: "borrowed servant" doctrine. Case in point:
      Parker v. Hosp. Auth. of City of Bainbridge 446 S.E.2d 766--GA (1994).

PMID- 7816925
TI  - Legal case briefs for nurses. MO: former nursing students sue college:
      misrepresentation and "fraud by silence"; NY: hospital has two separate sites:
      NLRB approves separate bargaining units.

PMID- 7816926
TI  - Information "lead" does not impact peer review privilege. Case in point: Mulder
      v. VanKersen 637 N.E.2d 1335--IN (1994).

PMID- 7816927
TI  - The peripheral nerve allograft: a comprehensive review of regeneration and
      neuroimmunology.

PMID- 7816928
TI  - Transport properties of vertebrate blood-nerve barrier: comparison with blood
      brain barrier.

PMID- 7816929
TI  - Functional development of the parasympathetic neurons of the avian ciliary
      ganglion: a classic model system for the study of neuronal differentiation and
      development.

PMID- 7816930
TI  - The motor innervation of mammalian muscle spindles.

PMID- 7816931
TI  - Experimental studies on the role of serotonin in cognition.

PMID- 7816932
TI  - The nature and origin of orientation specificity in neurons of the visual
      pathways.

PMID- 7816933
TI  - Amphibian sympathetic ganglia: an owner's and operator's manual.

PMID- 7816934
TI  - Secretory and synaptic vesicle membrane proteins and their possible roles in
      regulated exocytosis.

PMID- 7816935
TI  - A vitamin as neuromodulator: ascorbate release into the extracellular fluid of
      the brain regulates dopaminergic and glutamatergic transmission.
AB  - Ascorbate is an antioxidant vitamin that the brain accumulates from the blood
      supply and maintains at a relatively high concentration under widely varying
      conditions. Although neurons are known to use this vitamin in many different
      chemical and enzymatic reactions, only recently has sufficient evidence emerged
      to suggest a role for ascorbate in interneuronal communication. Ascorbate is
      released from glutamatergic neurons as part of the glutamate reuptake process, in
      which the high-affinity glutamate transporter exchanges ascorbate for glutamate.
      This heteroexchange process, which also may occur in glial cells, ensures a
      relatively high level of extracellular ascorbate in many forebrain regions.
      Ascorbate release is regulated, at least in part, by dopaminergic mechanisms,
      which appear to involve both the D1 and D2 family of dopamine receptors. Thus,
      amphetamine, GBR-12909, apomorphine, and the combined administration of D1 and D2
      agonists all facilitate ascorbate release from glutamatergic terminals in the
      neostriatum, and this effect is blocked by dopamine receptor antagonists. Even
      though the neostriatum itself contains a high concentration of dopamine
      receptors, the critical site for dopamine-mediated ascorbate release in the
      neostriatum is the substantia nigra. Intranigral dopamine regulates the activity
      of nigrothalamic efferents, which in turn regulate thalamocortical fibers and
      eventually the glutamatergic corticoneostriatal pathway. In addition,
      neostriatonigral fibers project to nigrothalamic efferents, completing a complex
      multisynaptic loop that plays a major role in neostriatal ascorbate release.
      Although extracellular ascorbate appears to modulate the synaptic action of
      dopamine, the mechanisms underlying this effect are unclear. Evidence from
      receptor binding studies suggests that ascorbate alters dopamine receptors either
      as an allosteric inhibitor or as an inducer of iron-dependent lipid peroxidation.
      The applicability of these studies to dopamine receptor function, however,
      remains to be established in view of reports that ascorbate can protect against
      lipid peroxidation in vivo. Nevertheless, ample behavioral evidence supports an
      antidopaminergic action of ascorbate. Systemic, intraventricular, or
      intraneostriatal ascorbate administration, for example, attenuates the behavioral
      effects of amphetamine and potentiates the behavioral response to haloperidol.
      Some of these behavioral effects, however, may be dose-dependent in that
      treatment with relatively low doses of ascorbate has been reported to enhance
      dopamine-mediated behaviors. Ascorbate also appears to modulate glutamatergic
      transmission in the neostriatum. In fact, by facilitating glutamate release,
      ascorbate may indirectly oppose the action of dopamine, though the nature of the
      neostriatal dopaminergic-glutamatergic interaction is far from settled. Ascorbate
      also may alter the redox state of the NMDA glutamate receptor thus block NMDA
      gated channel function.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7816936
TI  - Respiratory modulation in the activity of sympathetic neurones.

PMID- 7816937
TI  - The value of staging of neck nodes in patients treated with radiotherapy.

PMID- 7816938
TI  - Local control, TCD50 and dose-time prescription habits in radiotherapy of head
      and neck tumours.
AB  - Clinical data on head and neck tumours presented by Withers et al. (The hazard of
      accelerated tumour clonogen repopulation during radiotherapy. Acta Oncol. 27: 131
      146, 1988) are reexamined. Recently it was argued that the relationship between
      TCD50 and treatment time might be influenced by the practice of prescription
      [3,4]. This paper investigates the role of local tumour control rate in the
      interpretation of the data. In the genuine data set local tumour control rates
      were replaced by either tumour failure rate or by random numbers. TCD50 values
      were calculated from the original and these manipulated data and related to
      treatment duration. TCD50 increases with about 0.48 Gy/day in all cases. This
      unexpected result is explained by the lack of a dose-response relationship which
      causes a highly significant correlation between TCD50 and prescribed dose.
      Consistently, multiple regression analysis reveals a significant impact of
      prescribed dose (p < 0.0001) on TCD50 but not of treatment duration (p > 0.05).
      The increase of TCD50 with treatment time reflects solely dose-time prescription
      habits. The data provide no significant evidence either for an impact of
      treatment duration or for repopulation during radiotherapy in head and neck
      tumours. From this lack of evidence it may not be concluded that treatment
      duration is an unimportant parameter in radiotherapy.

PMID- 7816940
TI  - BW12C perturbs normal and tumour tissue oxygenation and blood flow in man.
AB  - The effects of escalating doses of BW12C on normal tissue and tumour blood flow
      and pO2 in patients were studied. BW12C infusion resulted in a significant
      reduction in median subcutaneous tissue pO2, and an increase in the proportion of
      hypoxic values (< or = 2.5 mmHg). In 8 of 9 patients with accessible tumours
      there was a significant reduction in pO2 during BW12C infusion, but no effect on
      the proportion of hypoxic values. A rapid decline in normal tissue pO2 in the
      first 10 min was associated with an increase in skin red cell flux and a
      reduction of normal subcutaneous tissue, muscle, and tumour red cell flux of 30
      50%, that was maintained throughout a subsequent 1-h infusion of BW12C. Tumour
      perfusion, as measured by dynamic computed tomography, was slightly reduced in
      five out of six patients studied during BW12C infusion. BW12C reduces both
      subcutaneous tissue and tumour pO2 in patients. Both haemoglobin modification and
      reduction in blood flow are probably associated with this effect.

PMID- 7816939
TI  - Dose-effect relations for local functional and structural changes of the lung
      after irradiation for malignant lymphoma.
AB  - PURPOSE: To estimate the dose-effect relations for local functional (ventilation
      and perfusion) and structural (density) changes of the lung, 3-4 months after
      irradiation. METHODS: Twenty-five patients with malignant lymphoma were
      irradiated with a (modified) mantle field to an average dose of 38 Gy, given in
      21 fractions. Single photon emission computed tomography (SPECT) ventilation (V)
      and perfusion (Q) scans, and CT scans were performed before and 3-4 months after
      radiation treatment. The three-dimensional dose distribution was calculated using
      the CT data. After correlation of SPECT and CT data sets, the average post
      treatment value of V, Q and lung density per voxel was calculated relative to the
      pre-treatment value, per dose interval of 4 Gy. Subsequently, the dose-effect
      relations in each patient were normalized to the average value per voxel in the
      dose interval of 0-12 Gy. In addition, in each dose interval of 4 Gy the fraction
      of patients with changes larger than 20% was calculated for all three parameters.
      The dose-effect relations for perfusion and ventilation normalized to the low
      dose regions, and the dose-incidence curves for the fraction of patients with
      changes larger than 20% were fitted for all three parameters, using a logistic
      model. RESULTS: Marked changes in the distribution of V and Q were found after
      irradiation. Prior to normalization to the low-dose regions, a change in V and Q
      was found in most patients in the dose interval of 0-12 Gy, varying from an
      increase of 37% to a decrease of 10%, which was followed by a decreasing trend at
      higher doses. The increase in the low-dose regions indicated a redistribution
      phenomenon, the magnitude of which was dependent of the irradiated volume. The
      logistic fit of the dose-effect relations for Q and V, normalized to the low-dose
      regions, resulted in values for D50 of 51 Gy and 54 Gy (given in 21 fractions on
      average), respectively, and for the steepness parameter k of 4.2 and 4.0,
      respectively. The logistic fit for the dose-incidence curves for Q, V and lung
      density resulted in values for D50 and k of 38 Gy, 37 Gy, 44 Gy and 10.3, 7.8 and
      9.4, respectively. CONCLUSIONS: With the combined use of SPECT and CT scans, we
      have obtained dose-effect relations for local functional and structural damage in
      the lung, 3-4 months after irradiation.

PMID- 7816941
TI  - Relative output factors of asymmetric megavoltage beams.
AB  - A new method for calculating output factors of asymmetric therapy fields is
      presented. The method uses the output factors of symmetric fields, as well as off
      axis ratios measured in air, to calculate the output factor for an arbitrary
      asymmetric field. Calculations have been checked by measurements in four photon
      beams (4-18 MV) of three different linear accelerators. The accuracy between the
      theory and the measurements is generally better than 1%. According to the
      preliminary results the method may also be suitable for megavoltage electron
      beams.

PMID- 7816942
TI  - The potential and limitations of the inverse radiotherapy technique.
AB  - The objective of the work presented in this paper is to explore the scope of the
      applicability of the inverse radiotherapy technique for designing optimized
      intensity distributions to achieve a desired dose distribution. A specified
      desired uniform dose to the target volume is inverted, subject to constraints on
      the surrounding normal tissue dose, to produce optimum intensity distributions in
      a set of beams arranged around the target volume. We employed the inverse
      technique and software developed by Bortfeld and evaluated results both
      qualitatively and quantitatively using dose distribution displays, dose-volume
      histograms and biological indices including tumor control probability and normal
      tissue complication probabilities. So far we have applied this methodology to
      prostate and lung treatment plans. For prostate the inverse technique produces
      satisfactory approximations of the desired dose distributions. However, for lung
      its performance is considerably inferior. Our investigations point to a number of
      factors for this difference, the primary ones being differences in the tolerance
      doses of neighboring normal tissues, magnitudes of volume effect, tissue
      architectures, and the achievability of the specified desired dose distributions.
      We conclude that, for certain clinical situations, it is not sufficient to
      specify the objectives of optimization purely in terms of the desired pattern of
      the dose. The objectives must also include dose-volume effects and biological
      indices. Furthermore, the mathematics of optimization must be able to incorporate
      these factors into the process. We find that the inverse technique is not
      suitable for situations where dose-volume considerations and biological indices
      are important and that other methods of optimization of intensity distributions
      should be explored.

PMID- 7816943
TI  - Response of the central nervous system to boron neutron capture irradiation:
      evaluation using rat spinal cord model.
AB  - The response of the central nervous system to boron neutron capture irradiation,
      with either p-boronophenylalanine (BPA) or borocaptate sodium (BSH) as neutron
      capture agents, has been assessed using a rat spinal cord model. The mean latency
      times for the development of myelopathy after irradiation with the thermal
      neutron beam-alone, or in combination with BPA or BSH, were 23.7 +/- 0.3, 21.8 +/
      0.4 and 19.6 +/- 0.4 weeks, respectively. The radiation-induced lesion in the
      spinal cord was characterised by white matter necrosis. Due to the variations in
      the microdistribution of different neutron capture agents in body tissues, it was
      considered inappropriate to define the biological effectiveness of the high LET
      radiation, resulting from the 10B(n, alpha)7Li neutron capture reaction, relative
      to photon radiation, using the term 'relative biological effectiveness' (RBE).
      The term 'compound biological effectiveness' (CBE) factor was used as an
      alternative. ED50 values for the various irradiation modalities were calculated
      from probit fitted dose effect curves. Expressed as total physical absorbed doses
      these values were 13.6 +/- 0.4, 30.3 +/- 2.7 and 13.8 +/- 0.5 Gy after
      irradiation with the thermal neutron beam alone, or the thermal neutron beam in
      combination with BSH or BPA, respectively. The RBE of the thermal neutron beam
      was 1.4 +/- 0.04. The microdistribution of the two neutron capture agents played
      a crucial role in the determination of the overall biological effect, after
      thermal neutron activation. BSH, which is excluded from the CNS parenchyma by the
      blood brain barrier, had a low CBE factor value of 0.46 +/- 0.5. BPA, on the
      other hand, which crosses the blood brain barrier and distributes in the CNS
      parenchyma, had a higher CBE factor value of 1.33 +/- 0.16.

PMID- 7816944
TI  - Quality control of radiotherapy centres in Europe: beam calibration.
AB  - A European Quality Assurance Network for external radiotherapy was set up. In
      this, several countries participated on a voluntary basis to elaborate common
      protocols, using joint infrastructure. The support for the co-ordination of the
      project was given by the EC committee 'Europe Against Cancer'. In the first step
      of the programme, beam outputs and beam qualities are checked with mailed
      thermoluminescent dosimeters following the protocol prepared by the IAEA. The
      results concerning 125 beams from 66 centres are analysed. Twenty-two beams
      presented minor deviations (3-6%) and 15 beams (4/48 60Co beams and 11/77 X-ray
      beams) from 11 centres presented major deviations (> or = 6%). The analysis shows
      that 16/22 minor deviations and all major deviations have been detected in
      centres which have not benefited from an external check during the last 5 years.
      In 14 out of 15 large deviations, the measured dose was smaller than the stated
      dose. In most centres with major deviation the physicists did not have the
      necessary experience and did not regularly calibrate the beams. In 6 out of 11
      centres there was no dosimeter or the dosimeter available had not been calibrated
      recently. In 3 centres, the physicist did not give any explanation.

PMID- 7816945
TI  - The use of ultrasound to measure breast thickness to select electron energies for
      breast boost radiotherapy.
AB  - Ultrasound has been used in 30 patients to measure breast thickness as a means of
      selecting the most appropriate electron energy for the boost in breast
      conservation radiotherapy. When compared with electron energies selected on the
      basis of clinical examination, the target volume was underdosed in 21/30
      patients. A major problem in the placement of an electron boost is the
      demarcation of the target volume.

PMID- 7816946
TI  - Dose effects of seeds placement deviations from pre-planned positions in
      ultrasound guided prostate implants.
AB  - The effects of random (drifting) errors in actual seed placement during prostate
      implants have been evaluated by using geometrically optimized implants of I-125
      and Pd-103 seeds. Results indicate that small random deviations in the seeds
      placement from the preplant position may affect the planned dose and beam
      profiles significantly.

PMID- 7816947
TI  - The effect on wedge factors of scattered radiation from the wedge.

PMID- 7816948
TI  - A factor to further reduce late tissue toxicity.

PMID- 7816949
TI  - Interpretive review of the potential adverse effects of chlorinated organic
      chemicals on human health and the environment. Report of an expert panel.

PMID- 7816951
TI  - ["Chairside" microbiological tests in periodontics].
AB  - Based on the specific plaque theory in periodontology, several chairside tests
      have been introduced for the microbiological examination of periodontal patients.
      For the majority of these patients, however, a standard therapy (root planing in
      combination with good oral hygiene) results in a favorable outcome. Therefore,
      only for a small minority of periodontal patients a microbiological analysis
      could possibly contribute to better treatment. For such patients, a choice can be
      made between a culture technique (which is labour intensive and has a long
      waiting time before an answer is available) and one of the chairside tests. The
      culture technique has the advantage to examine most of the flora. The chairside
      tests have the advantage of giving immediate results, but are limited to a small
      number of species or morphotypes. As long as the outcome of a microbiological
      examination in general cannot be translated into a more specific treatment
      strategy, the frequent use of microbial analyses should not be advocated. Since
      the validity of the chairside tests have yet to be fully examined through
      clinical trials, culturing should be the method of choice, because their
      antibiogram could lead to a more specific antibiotic therapy for the few patients
      in need.

PMID- 7816950
TI  - [Microbiological tests in the diagnosis of periodontal disease].
AB  - Today our knowledges concerning microbial aetiology and periodontal pathogeny
      allow us to use some tests in our private practice, that are different from those
      of yesterday. This article will attempt to review them.

PMID- 7816952
TI  - [Specimen collection in dental plaque and oral microbiology].
AB  - Plaque sampling is the first but also one of the most important steps in a
      microbiological examination. Different devices exist to take a sample, each with
      their own characteristics. Sterile paperpoints and curettes are most commonly
      used, but select a different flora. Isolation of the sample side is of utmost
      importance to prevent contamination, because the composition and concentration of
      the plaque differs from region to region (within the oral cavity but also within
      the pocket). Samples are collected and diluted in different fluids, of which
      Reduced Transport Fluid is preferred if an anaerobic culture procedure is
      planned.

PMID- 7816953
TI  - [Subgingival application of antibiotics: literature review].
AB  - Recently, several systems of topical antibiotic administration have been
      investigated. Most systems use sustained release devices to obtain high levels of
      antibiotics in the deepened periodontal pockets. Metronidazole and tetracycline
      can be administered without causing systemic side-effects. All systems summarized
      in this article are to be used after scaling and root planing of the diseased
      sites to increase the effect of the mechanical treatment.

PMID- 7816954
TI  - [Bacteriological aspects of periodontal disease].
AB  - Periodontal diseases are caused by specific bacteria in the periodontal pocket.
      Despite the vast complexity of the flora on the teeth and the more than 300 types
      of bacteria that may be found in the mouth, studies have been able to narrow the
      list of pathogens to a small group of suspected bacteria. It is not clear,
      however, how much of the destruction of periodontal tissue is caused by the
      direct effects of the bacteria and how much by indirect effects mediated by the
      host's reaction to the bacteria.

PMID- 7816955
TI  - [Salivary concentration of Streptococcus mutans in children and adolescents in
      Basel].
AB  - The search for a feasible method to estimate the caries risk in humans is going
      on since several years. Such risk assessments should especially be performed in
      persons clinically suspected to be at risk. The quantitative determination of
      Streptococcus mutants (SM) in whole saliva has been proposed to serve as a
      measure of the caries risk. SM tests have been performed in 1991 in a group of
      5743 5 to 16 year old children and adolescents living in the city of Basle.
      Levels of SM in whole saliva were correlated with caries prevalence both in the
      deciduous and permanent teeth. SM tests have equally become a helpful pedagogic
      instrument used to motivate patients for individual prophylactic activities.

PMID- 7816956
TI  - [The use of chlorhexidine varnish in the prevention of dental caries].
AB  - Dentistery recently has developed a new preventive treatment, that is the
      suppression of the acid-producing bacteria in dental plaque. The background and
      application of two chlorine hexidine lacquers, EC40 and Clorzoin are discussed.

PMID- 7816957
TI  - [Microbial diffusion by aerosol during ultrasonic scaling: descriptive study].
AB  - The aim of this study was to evaluate the bacterial spreading by using ultrasonic
      scaler and air-polisher. During ultrasonic scaling, bacterial spray is important
      near patient's mouth (30 cm), principally without good aspiration devices. In
      this case, clear spreading is observed at 2 m from the patient. Air-polishing
      compared to ultrasonic scaling produces larger microorganisms pollution.

PMID- 7816958
TI  - [Incidence and elimination of parietal smear layer in endodontics].
AB  - During canal preparation, the repeated passage of instruments provokes the
      formation of smear on the surface of the dentin. It is advisable to eliminate
      that, so as to increase antisepsis and filling impermeability. This is obtained
      by means of an irrigation, using a chelate compound of 6% citric acid for 60
      seconds, at the end of the preparation.

PMID- 7816960
TI  - [Epidemiology and medical assessment].

PMID- 7816959
TI  - [Is dental caries contagious?].
AB  - Results from microbiological studies and saliva analyses have now become valuable
      diagnostic aids which we could no longer imagine being without. They give us
      additional, objective information on the clinical and radiological examination of
      caries. These tests have also proved to be valuable pedagogical aids for
      motivating patients in individual prophylaxis. The question asked at the
      beginning, "Are caries infectious?" can be answered as follows: Yes, the
      possibility of transmitting caries exists mainly during the first three years of
      an infant's life and when the molars erupt in the sixth and twelfth years.
      Transmission is avoidable when one knows the various ways in which it is
      transmitted. Information on this and knowledge among the general public is still,
      however, in its infancy.

PMID- 7816961
TI  - [Economic analysis of neonatal screening for drepanocytosis in metropolitan
      France].
AB  - There is indisputable evidence that mortality and morbidity can be significantly
      reduced by programmes that screen newborns for sickle cell disease. But in the
      French epidemiological context, national decision regarding generalization of
      local screening programmes to all newborns must take into account economic
      considerations as at-risk populations represent, in most geographic areas, a few
      percent of the total population. Targeted screening can be considered but raises
      ethical and practical issues. In order to compare alternative screening
      strategies, a cost-effectiveness analysis has been performed. The analysis is
      based on a screening programme of newborns conducted in the south-eastern suburb
      of Paris. Strategies have been defined in terms of laboratory procedures
      (isoelectrofocalisation, electrophoresis on citrate agar, high pressure liquid
      chromatography, BIORAD technique,...) and methods for blood collection (dried
      paper, micro-tube). An evaluation of all the necessary costs have been performed
      for each strategy in the biochemistry laboratory in charge of the neonatal
      programme. Costs have been estimated from detailed observation of physical
      quantities of capital and labour involved in each case. Evolution of unit and
      marginal costs according to the level of annual production has been assessed.
      Effectiveness has been measured in terms of number of sickle cell cases detected.
      Screening of at-risk babies in Paris region would permit detection of 80 to 215
      babies each year at a unit cost per case found varying from 1 to 2,800 US$
      (according to hypothesis of prevalence). When compared with other programmes of
      prevention, results of selected screening of newborns in whole metropolitan
      France suggest that this action might be discussed by public health authorities.

PMID- 7816962
TI  - [Determination of the sensitivity of echography in prenatal diagnosis of fetal
      malformations. Methodological aspects].
AB  - In the article, following Eddy's work we show that the ratio of the number of
      cases detected by echography to the total number of cases is not a consistent
      estimator of test sensitivity of the pathology over time. In such conditions, the
      sensitivity of the test function is the only correct way to evaluate the test's
      ability to detect pathologic cases in an asymptomatic population. From a
      methodological point of view, if the time of detectability of the condition is
      considered as a random variable, then the function of sensitivity is estimated by
      fitting a distribution function to the observed date. In order to illustrate the
      feasibility and the consistency of our methodology, we present results based on
      simulated data.

PMID- 7816963
TI  - [Estimation by the Hui and Walter method of the sensitivity and specificity of a
      diagnostic test in the absence of a reference test: results of a simulation
      study].
AB  - Hui and Walter proposed an approach to directly estimate the parameters of
      diagnostic tests (sensitivity and specificity for dichotomous tests) and the
      prevalence of the disease in the absence of a reference error-free test, and
      without imposing any constraint. We performed a simulation study to investigate
      the finite-sample properties of the proposed estimators for the situation of
      three tests. We obtained the following results: i) in screening situations
      (prevalence < or = 0.10), severe bias and poor precision in the parameter
      estimates occur and this approach should not be used except for studies with a
      very large sample size (n > or = 2500); ii) in diagnostic situations (prevalence
      > or = 0.30), the approach is much more reliable and very little or no bias
      occurs even for small sample sizes (n = 50, 100), except when both the prevalence
      is very high (p > or = 0.90) and the performances of the tests mediocre
      (sensitivity and specificity lower than 0.80).

PMID- 7816964
TI  - [Implementation of an orodental prevention program in Auvergne: report after 1
      year].
AB  - A pilot program in preventive dentistry has been carried out since 1992 in
      Auvergne (France). In this program, children of artisans and shopkeepers from 4
      to 15 year-old have an annual dental consultation with the dentist of their
      choice. Dental care when related to dental caries prevention and treatment is
      free of charge. From September 1992 to September 1993, 48% of the 4 and 5 year
      old children (n = 1040) to whom the program had been addressed went to the
      dentist for this consultation. Preventive dental treatments such as sealants and
      professional topical fluoride applications were rarely performed. However, a
      fluoride support was prescribed to 70% of the participants. Moreover, 75% of the
      children displaying caries at the time of the first consultation received
      appropriate curative dental treatments.

PMID- 7816965
TI  - [Evaluation of the quality of management of urinary infections in children in
      ambulatory care].
AB  - The objective of this study was to describe the conditions in which urinary tract
      infections in children are managed by ambulatory medical services and compare the
      results with recommendations of experts in the field. For a period of one month,
      we focused on the methods of urine sample collection by observing 149 urinalyses
      for children under 15 in 13 private medical laboratories. Secondly, we
      investigated cases involving 26 prescribing physicians in order to assess
      treatment and additional testing on 28 children whose urine cultures showed
      significant bacterial growth. Urine samples were collected at home by parents in
      72% of the cases, often with defective procedures: improper antisepsis for pre
      collection cleansing in 65% of the cases, in 51% of the cases the maximum time
      lapse between the moment a collection-bag was applied and the moment the filled
      bag was removed was overrun. Compared with standard techniques, the quality of
      the samples was deemed questionable in 33% of cases and unacceptable in 41%.
      Attending physicians diagnosed urinary infections in 22 children. The antibiotic
      treatment prescribed to these children was apparently insufficient in 40% of the
      cases. Less than a third of the infected children benefited from a radiologic
      examination of the urinary tract. This study demonstrates that adherence to rules
      inherent in managing pediatric urinary infections is less than satisfactory in
      ambulatory medicine. It appears necessary to improve the quality of urinalysis by
      inciting laboratories to collect urine samples in laboratory. Physicians should
      also be better informed of the results of consensus conferences.

PMID- 7816966
TI  - [Mother-child transmission of hepatitis B virus in the Tunisian Sahel].
AB  - In order to assess the importance of mother-child transmission of the hepatitis B
      virus (HBV) in the Tunisian Sahel, 81 HBsAg-positive mothers have been selected
      at delivery in a representative sample of 1940 who delivered in maternities of
      this region. Each HBsAg-positive mother was matched for age and parity
      particularly with two HBsAg-negative mothers. Children born to these 66 HBsAg+
      and 120 HBsAg- mothers were traced at 28 months and tested by ELISA for HBV
      serologic markers (HBsAg, anti-HBs and anti-HBc). The distribution of these
      markers was significantly different according to the maternal status for HBsAg.
      The overall prevalence rate of HBV markers was higher in children born to HBsAg+
      mothers as compared to children born to HBsAg- mothers (33.3% vs 13.3%, OR = 2.5,
      95% CI:1.4-4.2). For HBsAg, the figures were 27.3% and 9.2% respectively (OR =
      2.9, 95% CI: 1.5-5.9). Given the prevalence rate of HBsAg in mothers (4.2%), the
      role of mother-child transmission in the spread of HBV infection and the
      intensity and precocity of horizontal transmission, systemic vaccination against
      HBV at birth should be recommended in the Tunisian Sahel in the context of the
      EPI. However this decision should take into account, in terms of cost/efficacy
      ratio, the other public health problems concerning this area.

PMID- 7816968
TI  - Trends in smoking prevalence from 1974 to 1986 in young adults in The
      Netherlands.
AB  - Data of two screening projects for cardiovascular risk factors were used to
      analyse trends in smoking behaviour in the Netherlands between 1974 and 1986. In
      1974-1980 about 30,000 men and women aged 37-43 years and in 1981-1986 about
      80,000 men aged 33-37 years in five different towns were screened. Among men,
      smoking prevalence decreased significantly during the study period in three of
      the five towns and remained more or less constant in the other two. The decrease
      was stronger in 1974-1980 (ca. 2 percentage points per year) than in 1981-1986
      (ca. 1 percentage point per year). Among women, smoking prevalence decreased at
      different rates in three of the towns and increased considerably in one town in
      the period 1974-1980. The smoking prevalence in 37-43 year old Dutch men and
      women amounted to 58-66% and 48-57% respectively in 1980. In 1986, the smoking
      prevalence was 48-58% in 33-37 year old men. Comparison with data from other
      countries showed that smoking prevalence among both men and women in the mid
      eighties was still high in the Netherlands.

PMID- 7816967
TI  - [Respiratory symptoms and function of coal miners presenting radiological
      pulmonary abnormalities].
AB  - Respiratory symptoms and lung function of 80 coal workers suspected of
      pneumoconiosis (pulmonary X-rays classified 0/1 or 1/0 according to International
      Labour Organisation classification) who worked for at least 10 years at face work
      (Ts) were studied in comparison with two control groups matched by age (+/- 2
      years), height (+/- 5 cm), weight (+/- 10 kg) and smoking habits: the Tn group
      constituted by 80 coal workers who worked for at least 10 years at face work with
      normal pulmonary X-rays, and the HTn group constituted by 80 underground miners
      who worked mainly out of face work with normal pulmonary X-rays. The frequencies
      of cough, expectoration, chronic bronchitis or dyspnoea were significantly higher
      in Ts group than in the two others. The one-second forced expiratory volume to
      vital capacity ratio (FEV1/VC) was lower, closing volume to vital capacity
      (CV/VC) or to total lung capacity ratios (CV/TLC) were higher in Ts group than in
      the control groups. Unexpectedly, vital capacity (VC), one-second forced
      expiratory volume (FEV1), total lung capacity (TLC), compliance, diffusing
      capacity (DLCO) referred to alveolar volume (VA) were higher. In Ts group, the
      small rounded opacities were noted in the top part of the lung (56.9%), the
      irregular ones were distributed on the entire lung (65.5%). There were no
      relation between the category of small opacities and respiratory symptoms or lung
      function.

PMID- 7816969
TI  - [Medical interns and AIDS: perceptions and attitudes in 3 French regions].
AB  - This study has been conducted to clarify certain issues regarding residency
      training with regard to acquired immunodeficiency syndrome (AIDS). The objective
      was to evaluate resident physicians' experiences in, and attitudes toward, the
      care of persons with AIDS in France. The design was a cross sectional study,
      using a self administered mailed questionnaire to 627 residents in 3 French
      areas: Ile-de-France, Nord-Pas de Calais and Province-Cote d'Azur, with a follow
      up of non responders. The subjects of this study were a random sample of
      residents in the second year of specialty medicine or family medicine residencies
      (biological residents, surgeons, public health residents and research residents
      were excluded). The response rate was 56%. More than half of residents indicated
      that their training was deficient in AIDS ambulatory care and less of 40% felt
      competent to provide usual and primary care for AIDS patients. The social and
      psychosocial aspect of care seems to be the greatest difficulties for them. About
      the half of residents reported at least one needle stock contaminated by a
      patient's blood. Needle stick injuries from patients known to have HIV infection
      were reported by 8% of them. About 25% expressed great concern about the
      professional risk of HIV contamination and 24% indicated it is dangerous to
      provide care for AIDS patients. It appears that an important component of future
      education in medical residency programs should emphasize strategies to address
      social and psychosocial issues in the medical care of AIDS patients and to
      decrease the risk of needle stick injuries.

PMID- 7816970
TI  - [Recent data on health status and health practices of French population].

PMID- 7816971
TI  - [New data on epidemiology of tuberculosis in 2 American metropolitan areas].

PMID- 7816972
TI  - [Has sperm quality decreased during the last 50 years?].

PMID- 7816973
TI  - [Health and cardiovascular diseases in women].

PMID- 7816974
TI  - [Peculiarities in the diagnosis of ischemic heart disease in women].

PMID- 7816975
TI  - [Prognosis of coronary disease in women].

PMID- 7816976
TI  - [Usefulness of estrogen treatment in prevention of ischemic heart disease in
      menopausal women].

PMID- 7816977
TI  - [Hypolipemic treatment in pre- and postmenopausal women].

PMID- 7816978
TI  - [Effect of thrombolytic treatment on the prognosis of myocardial infarct in
      females].

PMID- 7816979
TI  - [Percutaneous revascularization in women. Risks and results of different
      techniques of angioplasty].

PMID- 7816980
TI  - [Effects of sex on indications of surgical coronary revascularization. Technical
      characteristics and results in women].

PMID- 7816981
TI  - [Anticoagulation in pregnancy].

PMID- 7816982
TI  - [Epidemiology of coronary disease in women].

PMID- 7816983
TI  - [Differences in initial and long-term results of percutaneous mitral valvulotomy
      as a function of sex].

PMID- 7816984
TI  - [Influence of sex in the technique and results of valvular surgery].

PMID- 7816986
TI  - [Video-assisted thoracic surgery : fad or real progress?].

PMID- 7816985
TI  - [The heart and pregnancy].

PMID- 7816987
TI  - [Should passive smoking be recognized as carcinogenic?].

PMID- 7816988
TI  - [Asthma in infants].
AB  - Infant asthma is a newly individualised entity, underdiagnosed and undertreated.
      The physiological and anatomical features in infancy, the particular frequency of
      respiratory viral infections at this age can explain clinical aspects of asthma
      in infant. Some risk and prognostic factors, however, have been established.
      These include allergy, viral infections, neonatal respiratory illness. An early
      diagnosis of the disease makes possible adequate preventive means to be carried
      on. Treatment, based firstly on environmental control must be started soon to
      preserve pulmonary growth.

PMID- 7816989
TI  - [The p53 gene and protein in bronchial carcinogenesis:from biological to clinical
      aspects].
AB  - The p53 gene codes for a nuclear phosphoprotein which is capable of modulating
      the expression of certain genes implicated in the regulation of cell division.
      The mutation of an allele on the p53 gene with loss of the healthy allele, in
      different tissues such as lung, larynx, bladder, liver, skin, colon and breast,
      which may or may not be exposed to chemical or physical carcinogens (tobacco,
      radon, ultraviolet, aflatoxin B1), is associated with the occurrence of cancer.
      Indeed, the mutated p53 protein loses its anti-proliferative properties favouring
      a de-regulation of cellular multiplication with the accumulation of genetic
      aberrations. The homozygous deletion of the p53 gene in germ cells in the members
      of certain family cancers (Li-Fraumeni syndrome) leads to an increased incidence
      of cancers in the child or young adult. The most frequent mutations of the p53
      gene end in a stabilisation of the mutated protein with immuno-histochemical
      nuclear marking of the cells carrying such an alteration. In certain patients
      this stabilisation of the mutated protein ends in auto-immunisation with anti-p53
      serum antibodies. Bronchial cancer is a cancer of which the mutations of p53 are
      the most frequent (45-65% of bronchial cancer) as result of the mutagenic effect
      of tobacco smoke. These mutations seem to be associated with a bad prognosis and
      indeed to chemo-and radiotherapeutic resistance. The early diagnosis of p53
      alterations (in dysplastic lesions or tumours which are only slightly developed)
      would enable new therapeutic interventions in bronchial cancer such as gene
      therapy or radio-immunotherapy to either restore the p53 gene to normality or to
      eliminate the cells expressing the mutated p53 protein respectively.

PMID- 7816990
TI  - [Mycoplasma pneumoniae respiratory infections in hospitalized patients].
AB  - We report a study of 8 patients with acute Mycoplasma pneumoniae infection of the
      respiratory tract admitted to the Army Hospital Desgenettes over a 10 months
      period. Our clinical observations are compared with a review of the literature.
      We observed a seasonal outbreak in spring and autumn. This infection was
      encountered mainly in young people. The two most common clinical findings were
      cough and fever. Our report describes mild forms of this disease. Definitive
      etiological diagnosis is based on a four-fold or higher rise in titers. The
      macrolides or tetracyclines remain the most effective antibiotics.

PMID- 7816991
TI  - [Effect of an inhaled beta-2-adrenergic agent administered at the time of delayed
      bronchial reactions to occupational agents].
AB  - We previously showed in a retrospective study that the acute response to an
      inhaled beta-2-adrenergic agent is marked in late asthmatic reactions (J Allergy
      Clin Immunology 1990;85:834). In a double-blind prospective study, we assessed
      the magnitude and duration of the effect of inhaled salbutamol (200 micrograms)
      compared to a placebo in 22 subjects who experienced late asthmatic reactions
      (sustained fall in FEV 1 > or = 20%) after specific inhalation challenges in the
      laboratory with various occupational agents (isocyanates in 9 subjects). Before
      salbutamol was administered, the % in FEV1 over the pre-challenge values did not
      differ between the placebo (31 +/- 8%, n = 12) and the active (28 +/- 6%, n = 10)
      groups. The % recovery in FEV1 over the pre-bronchodilator value was 9 +/- 11% in
      the placebo group and 28 +/- 11% in the active group (t = 4.0, p < 0.001). The %
      recovery in FEV1 assessed in comparison with pre-challenge values was up to 80 +/
      17% in the placebo group and up to 95 +/- 6% in the active group (t = 2.85, p <
      0.01). The 10 subjects on active medication had FEV1 values > or = 80% of the pre
      challenge value one hour after inhaling salbutamol. The pattern of diminution in
      the bronchodilator effect was similar in the eight subjects with occupational
      asthma on active medication who remained for more than one hour as compared to a
      control group of asthmatic subjects paired for the degree of baseline airway
      obstruction. These data show that late asthmatic reactions are satisfactorily
      reversed with inhaled bronchodilator and that the duration of the effect is as
      satisfactory for subjects with occupational asthma as it is for asthmatic
      subjects.

PMID- 7816992
TI  - [Inhaled corticotherapy sparing effect by sodium nedocromil in moderate to severe
      asthma].
AB  - BACKGROUND: The increased use of high dose inhaled steroid in the treatment of
      asthma has revealed the risk of dose-dependent side effects. Nedocromil sodium is
      a non steroidal agent with anti-inflammatory properties. OBJECTIVE: To
      demonstrate whether nedocromil sodium may have some therapeutic benefit in
      asthmatic patients treated with high dose inhaled steroids and whether it has an
      inhaled steroid sparing effect. PATIENTS: 134 adults with moderate to severe
      asthma not adequately controlled with high dose inhaled steroids (750 to 1,500
      micrograms/day). METHOD: After a two week baseline period, patients were
      randomized to receive either nedocromil sodium (4 mg qid) or placebo for 24 weeks
      in a double blind fashion. During the first 12 weeks of treatment, the dose of
      inhaled steroid was maintained constant whereas it was altered during the last 12
      weeks according to asthma scores. RESULTS: Among 108 patients reaching the
      reduction phase, a decrease of 250 micrograms of inhaled steroid or more was
      possible in 79% of patients on nedocromil sodium and in 60% of patients on
      placebo (p < 0.03). Symptoms scores were improved on both treatments during the
      12 first weeks, more on nedocromil sodium than on placebo, treatment difference
      reaching significance for daytime asthma (p < 0.02). FEV1 improved during the
      trial for patients on nedocromil (from 69 +/- 18% to 74 +/- 21%; p < 0.005)
      whereas it did not for those on placebo. CONCLUSION: Nedocromil sodium is
      effective in improving moderate to severe asthma in addition to inhaled steroid
      and has some steroid sparing effect in patients treated with high dose inhaled
      steroid.

PMID- 7816993
TI  - [Value of individualized rehabilitation at the ventilatory threshold level in
      moderately severe chronic obstructive pulmonary disease].
AB  - In order to study the efficiency of individual training programs at the
      ventilatory threshold level, twenty COPD patients were randomized into two groups
      and studied over a two-month period. At the start, during, and at the end of the
      study all subjects performed incremental exercise tests. The trained group (59.60
      SEM +/- 2.75 years) walked four times a week at the heart rate corresponding to
      the metabolic level of ventilatory threshold. The other group served as controls
      (58.2 +/- 1.80 years). A marked increase in the symptom-limited oxygen
      consumption (+/- 25%) (p < 0.01), the maximal ventilation (+20%) (p < 0.01), and
      the ventilatory threshold (+19%) (p < 0.05) was found in the trained group. No
      modification was recorded in the control group. The ventilatory pattern at
      submaximal intensities expressed in percentage of the initial oxygen consumption
      showed significant differences between groups, the trained-group ventilation
      decreased at 50% and 75% VO2 sl (p < 0.05). The breathing frequency also
      decreased at 50% and 75% VO2 sl (p > 0.05). Moreover, we observed an increase in
      the oxygen pulse at 50% VO2 sl (p < 0.05). In conclusion, this study demonstrates
      that individualized training at the ventilatory threshold level increases
      exercise tolerance and produces better ventilatory comfort in COPD patients.

PMID- 7816994
TI  - [Indolent mastocytosis and bronchial hyperreactivity. A case report].
AB  - Mastocytosis (MS) may be exclusively cutaneous or, more rarely, systemic. MS may
      be indolent (benign), aggressive, leukaemic or associated with a
      myeloproliferative disorder. The clinical expression of MS may be secondary to
      the direct consequences of the development of mastocytes in tissue or correspond
      to the paroxysmal features related to the liberation of vasoactive and
      spasmogenic mediators by activated mastocytes. Dyspnoeic episodes are classical
      but the physiopathological mechanism is poorly documented. True asthma or
      bronchopulmonary mastocytosis seems rare. The authors report evidence of non
      specific bronchial hyper-reactivity (HRB) to Carbachol in a patient effected with
      benign cutaneous mastocytosis with secondary elevation of the total serum IGE.
      Factors determining the HIB are discussed and appear primarily linked to the
      mastocytosis.

PMID- 7816995
TI  - [Treatment with intermittent high dosage corticotherapy in chronic interstitial
      pneumonia in an infant. A case report].
AB  - Chronic interstitial pneumonia (PIC) are rare in infants. We report a case of an
      infant who presented with a chronic interstitial pneumonia following an infection
      with a respiratory syncytial virus. The diagnosis was confirmed histologically
      (open lung biopsy). The failure of oral steroid therapy (Prednisolone 2
      mg/kg/day) led to the use of boluses of methylprednisone (30 mg/kg/day, daily for
      three days in three series one month apart). The treatment led to a progressive
      improvement and thirty months after the last bolus the respiratory examination
      was normal as was the radiology. The efficacy of bolus steroid therapy observed
      by other authors should be confirmed in multicentre trials using surgical biopsy
      to precise the pulmonary lesions.

PMID- 7816996
TI  - [Thoracoscopic resection of a voluminous dermoid cyst of the mediastinum, using a
      3-dimensional imaging system].
AB  - A case of a young patient who was operated on of a large dermoid cyst of the
      anterior mediastinum is reported. During this procedure, a new three-dimensional
      imaging system was used. This case-report confirms the usefulness of thoracoscopy
      for benign mediastinal tumors removal and points out the benefit of three
      dimensional endoscopy for dissection of tumors having complex anatomical
      connections.

PMID- 7816997
TI  - [Delayed detection of cystic fibrosis in a patient with Mycobacterium avium
      complex infection].
AB  - We report a case of pulmonary infection by Mycobacterium avium complex revealing
      in a 21 years old patient a cystic fibrosis heterozygous for the delta F 508
      deletion. The role of this bacteria in the lung infection is suggested by
      repeated isolation. This infection caused bronchitis, hypoxemia and pulmonary
      nodules at CT scan. The clinical and radiological signs improved after treatment
      with four antibiotics whereas only clarithromycin showed in vitro activity. An
      obstructive disease due to allergic bronchopulmonary aspergillosis developed and
      was controlled by steroid therapy.

PMID- 7816998
TI  - [Peritoneal pseudomyxoma with pleural metastases. A case report].
AB  - The authors report a case of a 69 year old man with a peritoneal pseudo-myxoma
      probably secondary to a mucocele of the appendix and complicated by pleural
      metastases which were nodular, unilateral and asymptomatic. These were discovered
      on computerised tomography during examination for the recurrence of the
      peritoneal disease. A study of the histology of the pleural fragments obtained by
      thoracotomy showed the presence of lesions which were identical to those found in
      the peritoneal masses.

PMID- 7816999
TI  - [Chronic middle lobe pneumopathy].

PMID- 7817000
TI  - [Pleural needle biopsy].

PMID- 7817001
TI  - Development of an enzyme-linked immunosorbent assay for the detection of IgG
      subclasses in the serum of normal and diseased dogs.
AB  - The present study describes the development of an enzyme-linked immunosorbent
      assay capable of quantifying serum antibody of all four canine IgG subclasses. A
      panel of subclass-restricted and subclass-specific monoclonal antibodies was used
      to measure IgG subclasses in the serum of healthy dogs, as well as in dogs with a
      range of clinical diseases. The subclasses have been redefined as IgG1, IgG2,
      IgG3 and IgG4 based on a comparison with the relative concentration and
      electrophoretic mobilities of human IgG subclasses. In serum samples from healthy
      dogs, the concentration of IgG1 (mean, 8.17 +/- 0.95 mg ml-1) and IgG2 (mean,
      8.15 +/- 3.16 mg ml-1) were very similar and considerably higher than the levels
      of IgG3 (mean, 0.36 +/- 0.43 mg ml-1) and IgG4 (mean, 0.95 +/- 0.45 mg ml-1).
      There was no apparent difference in the level of subclasses between the different
      breeds comprising this normal population. Sera from dogs with a range of immune
      mediated or inflammatory diseases all had markedly elevated levels of IgG2 (more
      than 13 mg ml-1), but IgG1 decreased (less than 4 mg ml-1) to levels below the
      normal range.

PMID- 7817002
TI  - Immunoelectron microscopical demonstration of the absorption of colostral IgG by
      small intestinal enterocytes in newborn rats.
AB  - The protein A-gold technique was used in the cranial, transitional and caudal
      segments of the small intestine of 12 newborn rats to demonstrate the process of
      absorption of gold-labelled IgG through the enterocytes. The observation of the
      attachment of labelled IgG molecules to the wall of coated vesicles suggested a
      receptor-mediated transport of colostral IgG in the cranial segment of the small
      intestine. However, intracellular micropinocytotic transport predominated in the
      transitional and caudal segments of the small intestine. There was no evidence
      for paracellular transport. Lysosomal structures in the enterocytes did not
      appear to impede the absorptive activity during the absorption period, which
      lasted 20 days.

PMID- 7817003
TI  - Age-dependent immune response in Merino sheep.
AB  - The numerical and functional attributes of populations of lymphocytes were
      compared in the blood, lymph and skin of young and mature sheep. Young sheep,
      four to eight months old, had a lower proportion of CD4+ cells in blood, lymph
      and skin than mature sheep three to six years old. In contrast, B cells and T19+
      cells were as prevalent or more prevalent in young sheep as in mature sheep.
      Blood lymphocytes from young sheep, cultured in vitro produced less interferon
      gamma, both spontaneously and in the presence of concanavalin A than did
      lymphocytes from older sheep. The serum antibody responses of adult sheep to the
      T cell-independent antigen Brucella abortus lipopolysaccharide (LPS) were greater
      over a range of antigen doses, suggesting that an apparent excess of antigen
      could not overcome the relative immune deficiency of young sheep. The adjuvant
      Quil A corrected the depressed antibody response of young sheep to B abortus LPS,
      but dextran sulphate did not. The skin contact hypersensitivity of mature sheep
      to dinitrochlorobenzene was greater. However, the T cell phenotypes present in
      infiltrates of lymphocytes elicited by the intradermal injection of tetanus and
      diphtheria, but not tuberculin antigens, were comparable for the two age groups.
      The capacity of Quil A to raise the antibody responses of both young and mature
      sheep to a similar titre suggests that it may be possible to overcome the
      immunological hyporesponsiveness that may contribute to the disease
      susceptibility of young sheep.

PMID- 7817004
TI  - Schultz-Dale reaction in isolated perfused calf ear and its inhibition by
      isoproterenol.
AB  - Calf ears which were sensitised to horse serum and others which were unsensitised
      were catheterised and perfused at a constant flow rate of 2 ml min-1 with Krebs
      Henseleit solution using a peristalic pump. The ear preparations were then
      challenged with whole horse serum, the sensitising antigen. Vascular responses
      were monitored as changes in perfusion pressure. Weight changes were determined
      to indicate the extent of oedema formation. Unsensitised ear preparations
      responded to 0.1 ml whole horse serum with 43.3 +/- 0.8 per cent (n = 5) and 10.7
      +/- 0.3 per cent (n = 5) increases in perfusion pressure and weight,
      respectively. Sensitised ear preparations responded to 0.05 ml whole horse serum
      by increases of 280.8 +/- 32.9 per cent (n = 5) and 27.2 +/- 1.4 per cent (n = 5)
      in perfusion pressure and bodyweight, respectively. Isoproterenol (10(-5) M)
      inhibited the vascular responses by 81.4 +/- 7.6 per cent (n = 5) while the
      increases in weight were reduced by 20.0 +/- 1.5 per cent (n = 5). The Schultz
      Dale reaction has thus been demonstrated in an isolated whole organ, the pinna.

PMID- 7817005
TI  - Flow cytometric analysis of bovine CD4 and CD8 lymphocytes: influence of blood
      sampling and processing methods.
AB  - Technical information to facilitate bovine blood treatment for optimum lymphocyte
      flow cytometry analysis is reported. Murine monoclonal antibodies CC8 and CC63
      were used to identify phenotypes corresponding to bovine CD4 T cells and CD8 T
      cells. Blood samples collected in acid citrate dextrose (ACD) enhanced leucocyte
      subpopulation separation compared with ethylenediamine tetra-acetic acid, heparin
      and sodium citrate. To preserve bovine blood before immunophenotyping, samples
      collected in ACD may be kept at 22 degrees C or at 4 degrees C and should be
      analysed within 32 hours. For isolation of white blood cells, whole blood lysis
      was faster and gave the same results as Ficoll gradient separation 1.077 and
      Ficoll gradient separation 1.083. After immunophenotyping, blood could be stored
      at 4 degrees C if fixed with paraformaldehyde within seven days. Owing to diurnal
      variations, blood should be collected at a standard time of the day.

PMID- 7817006
TI  - Respiratory burst activity associated with phagocytosis of Ehrlichia risticii by
      mouse peritoneal macrophages.
AB  - Peritoneal macrophages from two strains of mice, BALB/c and C3H/HeN, were
      analysed by flow cytometry for a respiratory burst associated with the
      phagocytosis of Ehrlichia risticii. Resident murine peritoneal macrophages failed
      to respond with a respiratory burst after phagocytosing E risticii. In contrast,
      mice previously infected with E risticii yielded peritoneal macrophages that did
      generate a respiratory burst on phagocytosing ehrlichiae.

PMID- 7817008
TI  - Comparison of pestivirus multiplication in cells of different species.
AB  - Twenty-four pestiviruses, comprising 11 from pigs, eight from cattle and five
      from sheep, were tested for their ability to replicate in cells of porcine,
      bovine and ovine origin. Seven of the viruses were successfully passaged in all
      three cell types. Four porcine isolates (hog cholera virus) replicated to
      significant titres only in porcine cells. One bovine virus grew well in bovine
      cells but only poorly in ovine cells and not at all in porcine cells. The
      remaining 12 viruses could replicate in cells from two of the three host species.
      The pattern of replication in different cell types varied between different
      isolates of the same virus species.

PMID- 7817007
TI  - Bovine ketosis and somatotrophin: risk factors for ketosis and effects of ketosis
      on health and production.
AB  - Aspects of the metabolism and health of 63 cows which had been treated with
      different amounts of bovine somatotrophin (BST) daily in the preceding lactation
      and 25 control cows were studied. The aims of the study were first, to identify
      cows with ketotic conditions, either by measurements of blood metabolite
      concentrations or by clinical observations, secondly, to evaluate the risk of
      such conditions in cows treated with BST in the preceding lactation, and thirdly,
      to examine the metabolic and production consequences of the ketotic conditions in
      an environment in which the cows' health, body condition and nutrition were
      closely observed. The cows were categorised objectively by the use of cluster
      analysis into non-ketotic cows and ketonaemic cows, on the basis of their plasma
      metabolite concentrations. Twelve of the control cows and none of the cows
      previously treated with BST were classified as ketonaemic. Similarly, nine of the
      control cows but only two of the cows previously treated with BST had clinical
      ketosis. Some, but not all, of the decrease in the risk of clinical ketosis was
      attributable to the lower body condition score of the cows previously treated
      with BST. The clinically ketotic cows had a greater risk of other illness in the
      first 10 days post partum than their herdmates, but the ketonaemic cows had a
      significantly lower risk of other disease in the first 10 days post partum. The
      ketonaemic control cows were significantly heavier than the non-ketotic control
      cows, but they maintained a higher dry matter intake than the latter cows,
      probably a key factor in reducing the risk of clinical ketosis.

PMID- 7817009
TI  - Further studies on the development and survival at low temperatures of the free
      living stages of Trichostrongylus tenuis.
AB  - To assess the ability of the free living stages of Trichostrongylus tenuis, a
      pathogen of red grouse, to survive the winter in significant numbers, the
      temperatures prevailing during the autumn, winter and spring of 1991-92 on the
      North Yorkshire moors were simulated in an incubator into which replicate
      cultures of T tenuis eggs were placed at intervals. September and early October
      eggs developed into larvae which survived over winter and were infective the
      following spring. Few November to February eggs survived to become larvae but
      early March eggs were reasonably successful. Continuous temperatures of -15
      degrees C were lethal to infective larvae within 12 days, but significant numbers
      of larvae survived temperatures of -10 degrees C or higher for up to three weeks
      and remained infective.

PMID- 7817010
TI  - Effect of 3'azido-2',3'-deoxythymidine (AZT) on experimental feline
      immunodeficiency virus infection in domestic cats.
AB  - The compound 3'azido-2',3'-deoxythymidine (AZT) inhibits the replication of
      feline immunodeficiency virus (FIV) in cell culture, and treatment with the
      compound has been reported to induce some clinical improvement in some cases of
      feline FIV infection. In order to determine the effect of prophylactic treatment
      with AZT on experimental FIV infection, cats were treated with the compound at
      0.2, 1.0, 5, 25 or 50 mg kg-1 day-1 for 29 days. One day after the treatment was
      started, they were inoculated with 150 cat infectious doses of FIV. All the cats
      became viraemic, seroconverted and developed lymphadenopathy, although the onset
      of each was delayed in the cats given higher doses of AZT. Anaemia developed in
      the cats given high doses of AZT. Virus re-isolated from the cats given 50 mg kg
      1 day-1 was as susceptible to AZT in cell culture as the inoculated virus. Thus
      AZT is much less effective in cats than might have been expected from the results
      of in vitro studies.

PMID- 7817011
TI  - Application of monoclonal antibody-based sandwich ELISAs to detect verotoxins in
      cattle faeces.
AB  - b1p4wich ELISAs, which use monoclonal antibodies for both the capture and the
      completion stages, were developed for the detection of verotoxins I and II (non
      variant). The ELISAs were used to investigate the incidence of verotoxins in 304
      samples of bovine faeces collected from cases of enteritis, and 113 samples
      collected from normal animals. For most samples, the tests were carried out
      directly on faeces, and on colony sweeps which were taken from cultures grown
      from the faeces. These colonies were either grown directly from faeces (mixed
      colony sweep) or from a coliform culture purified from this (purified colony
      sweep). All the positive ELISA reactions were investigated by Vero cell
      cytotoxicity assays for the confirmation of verotoxins. The largest numbers of
      ELISA-positive reactions which were confirmed by cytotoxicity assays were
      obtained with mixed colony sweeps. Verotoxin activity was confirmed in 74 (24 per
      cent) of the samples from cases of enteritis and from 35 (31 per cent) of the
      normal faeces samples. The occurrence of ELISA reactions unconfirmed by
      cytotoxicity assays and high cytotoxicity levels with low ELISA readings
      indicated the presence of non-toxic verotoxin epitopes and the presence of toxic
      verotoxin variants in the samples.

PMID- 7817012
TI  - Gait and respiration in standardbred horses when pacing and galloping.
AB  - The relationship between gait and the respiratory response to exercise was
      examined in five standardbred racehorses which exercised on a treadmill at a pace
      and a gallop. After an initial warm-up, respiratory rate and stride frequency
      were measured after one and two minutes of treadmill exercise at 80 per cent of
      maximal oxygen consumption (VO2max), after one minute at 100 per cent VO2max and
      after two minutes at 100 per cent VO2max (galloping horses only). Exercise at 100
      per cent VO2max continued until the horses showed signs of fatigue. Arterial
      blood was collected during exercise and when they were fatigued for the
      measurement of oxygen and carbon dioxide tensions, haemoglobin saturation and pH.
      Venous blood temperature was also recorded. The mean (SE) time to signs of
      fatigue was significantly (P < 0.05) less in the pacing horses (7.2 [0.4]
      minutes) than in the galloping horses (8.0 [0.4] minutes). The mean (SE) resting
      PCO2 was 47.7 (1.9) torr. During the pacing and galloping exercises at 80 per
      cent and 100 per cent VO2max the PCO2 remained in the range of 41.1 to 66.8 torr,
      despite concurrent hyperthermia and acidosis. The PCO2 during exercise was not
      significantly dependent on gait or exercise intensity. The PO2 was significantly
      higher in pacing horses during exercise at 80 per cent VO2max (111 [7] vs 96 [6]
      torr). The mean (SE) arterial blood pH decreased from 7.428 (0.025) during pacing
      at 5 m sec-1 to 7.250 (0.042) when the horses were fatigued.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7817013
TI  - A simple identification scheme for coagulase negative staphylococci from bovine
      mastitis.
AB  - Coagulase-negative staphylococci from cases of bovine mastitis were identified to
      species level by using an identification scheme based on a three-plate test
      system which tested for DNase on DNA agar, for protease on calcium caseinate
      agar, and for the organism's sensitivity to novobiocin, desferrioxaminine
      (deferoxamine) and fosfomycin by agar diffusion tests. Testing for the inhibition
      of Staphylococcus delta haemolysin (Skalka 1991) can replace the protease tests.

PMID- 7817014
TI  - Absorption of lincomycin through the respiratory pathways and its influence on
      alveolar macrophages after aerosol administration to chickens.
AB  - A concentration of 250 mg m-3 lincomycin was administered by aerosol to 40
      chickens, weighing between 1900 and 2200 g. The birds were killed in groups of
      five at different intervals after dosing, and the trachea, lungs and blood serum
      were examined for antibiotic content by bioassay. The antibiotic was present at
      high levels in the trachea for one to 24 hours, and significant levels were
      present in the lungs and serum. Respiratory macrophages were obtained from the
      lungs and air sacs of the chickens by lavaging through the surgically prepared
      trachea with a paediatric urinary catheter. The macrophages were identified by
      morphology as round or slightly amorphous, refractile, frequently grannular
      cells; they phagocytosed Staphylococcus aureus 6538.

PMID- 7817015
TI  - Tubular vimentin metaplasia in canine nephropathies.
AB  - The expression of the intermediate filament vimentin was examined
      immunocytochemically in 17 cases of histologically confirmed primary canine
      nephropathy, and compared with its expression in normal canine kidney. In normal
      renal tissue, the expression of vimentin was restricted to glomerular elements,
      but in all cases of chronic interstitial nephritis it extended to the cortical
      tubular epithelia, and was correlated with the degree of tubulo-interstitial
      damage. Three of four cases of renal cell carcinoma had vimentin reactivity in
      neoplastic cells. In only one case of familial renal disease was vimentin
      expressed in scattered epithelial cells of the cortical tubules.

PMID- 7817016
TI  - Plasma atrial natriuretic peptide in normal calves during the first 10 days of
      life.
AB  - The concentration and molecular form of the plasma atrial natriuretic peptide
      (ANP) in normal calves during the first 10 days of life were investigated. The
      mean (SEM) ANP concentration on the day of birth was 62.7 (5.52) pmol litre-1,
      and thereafter it decreased progressively and significantly (P < 0.001). After 10
      days, the plasma ANP concentration had decreased to normal adult values (11.3
      [3.87] pmol litre-1). On the day of birth and 10 days later a single peak
      corresponding to alpha-ANP alone was detected in the plasma of the calves.

PMID- 7817017
TI  - Pharmacokinetics of diminazene in plasma and cerebrospinal fluid of goats.
AB  - The pharmacokinetics of diminazene in the cerebrospinal fluid (CSF) and plasma of
      five uninfected goats treated with single intramuscular doses of 3.5 mg
      diminazene base kg-1 bodyweight was investigated. The concentrations of the drug
      were determined by high performance liquid chromatography, and were three to four
      times lower in CSF than in plasma. The kinetics of the drug in CSF and plasma
      differed significantly with respect to Cmax, tmax, AUC0-48h, AUMC0-48h, Cl and
      Vd(ss).

PMID- 7817018
TI  - Experimental infection of dogs with Borrelia burgdorferi.
AB  - Four beagle dogs were inoculated subcutaneously with the BITs1 Italian strain of
      Borrelia burgdorferi. Only one dog became infected and B burgdorferi was isolated
      from its blood and urine three and four weeks after infection. B burgdorferi
      antibodies were detected by immunofluorescence from four to 11 weeks after
      infection. An uninoculated dog kept in the same run as the infected dog,
      developed a positive serological response, but none of the five dogs showed
      clinical signs.

PMID- 7817019
TI  - Serotypes and putative virulence markers of Streptococcus suis isolates from cats
      and dogs.
AB  - Thirteen isolates of Streptococcus suis from cats and dogs were characterised.
      Formamide extracts of 10 of the 13 cultures reacted with group D specific
      antiserum, and serotyping of the cultures with specific antisera against capsular
      types 1 to 28 revealed the serotypes 9, 20, 1/2, 22, 26 and 4; the remaining
      cultures were untypable. In addition one of the cultures reacted with monoclonal
      antibodies against muramidase-released protein and in parallel with monoclonal
      antibodies against the extracellular factor (EF) of S suis. The latter reacted
      with proteins with a molecular weight of more than 150,000 indicating that the
      strain exhibited EF-related proteins. One of the 13 cultures haemagglutinated
      erythrocytes from human beings and various animal species and adhered in large
      numbers to HeLa cells.

PMID- 7817020
TI  - Quantitation of alpha-1 proteinase inhibitor in the pulmonary epithelial lining
      fluid of horses with chronic obstructive pulmonary disease.
AB  - The concentration of alpha-1 proteinase inhibitor (API) was measured in the
      pulmonary epithelial lining fluid (PELF) of horses with chronic obstructive
      pulmonary disease (COPD) while they had clinical signs and while they had none.
      The concentrations of total protein, albumin and API were significantly higher in
      the PELF of animals with clinical signs of COPD. The correlation between albumin
      and API in the PELF suggested that most of the API was derived from the serum.

PMID- 7817021
TI  - In memoriam Edward W. D. Norton, MD 1922-1994.

PMID- 7817022
TI  - Treatment of endophthalmitis after cataract extraction.
AB  - BACKGROUND: A series of 34 patients was prospectively treated for postoperative
      endophthalmitis according to a specific protocol. The data are from the pilot
      study performed before initiation of the Endophthalmitis Vitrectomy Study (EVS).
      METHODS: Patients with bacterial endophthalmitis that developed within 6 weeks of
      cataract extraction received intravitreal amikacin and vancomycin,
      subconjunctival and topical antimicrobials and corticosteroids, and systemic
      corticosteroids. All patients had diagnostic samples removed from the aqueous and
      vitreous, with randomized assignment to immediate vitrectomy versus vitreous tap
      and treatment with or without intravenous antibiotics. Outcome was evaluated 3
      and 9 months after treatment. RESULTS: At the 9-month visit, visual acuity was
      20/50 or better in 49% of all eyes, 20/200 or better in 79%, and 5/200 or better
      in 91%. Media clarity was such that a "20/40 or better view" of the retina was
      present in 71% of patients at 3 months and in 97% at 9 months. CONCLUSION: This
      is one of the largest series of patients with postoperative endophthalmitis
      treated and evaluated under a prospective protocol and without selection bias.
      Each of the options used in this study to treat postoperative endophthalmitis may
      result in good visual results.

PMID- 7817023
TI  - Use of the potential acuity meter and laser interferometer to predict visual
      acuity after macular hole surgery.
AB  - PURPOSE: As reported anatomic success rates for macular hole surgery increase, a
      method of accurately predicting postoperative visual acuity has increased
      clinical utility. METHODS: A series of 18 patients undergoing vitrectomy for
      idiopathic macular holes was evaluated prospectively for best refracted
      preoperative visual acuity, potential acuity meter (PAM) reading, and laser
      interferometer (LI) reading. Best refracted visual acuity after surgery was
      recorded and analyzed to assess the predictive value of the PAM and LI readings.
      RESULTS: The LI correctly predicted the final visual result in 6 of the 10
      patients who achieved a final visual acuity of 20/50 or better (P = < 0.011). The
      PAM did not accurately predict postoperative visual acuity for any of the eyes
      with a final visual acuity of 20/50 or better. Both correctly predicted outcome
      in the 7 patients with final visual acuity worse than 20/50. The LI prediction
      was within 2 lines of final visual acuity in 12 (70%) of 17 anatomically
      successful cases, and the PAM was within 2 lines of final visual acuity in 11
      (64%) of 17 cases. CONCLUSION: Both the LI and PAM were modestly accurate in
      predicting final visual acuity after macular hole surgery, but the LI was more
      accurate in predicting a visual acuity of 20/50 or better.

PMID- 7817024
TI  - The expanding role of laser photocoagulation for intraocular tumors. The 1993 H.
      Christian Zweng Memorial Lecture.
AB  - BACKGROUND: Methods of management for intraocular tumors include observation,
      radiotherapy, surgery, and laser therapy. Indications for and techniques of laser
      photocoagulation in the management of intraocular tumors have never been clearly
      defined in one report, however. METHODS: A review of selected cases of choroidal
      and retinal tumors treated with laser therapy between 1974 and 1993 was
      conducted, as was the literature on laser treatment of intraocular tumors. Based
      on these observations, indications for, techniques of, and results of laser
      treatment of selected intraocular tumors are discussed. RESULTS: The results
      suggest that the preferred technique of laser treatment varies with the type of
      tumor. Small melanomas are treated by two or three sessions of laser around the
      tumor and subsequent heavy treatment directly to the tumor. Choroidal nevus with
      serous detachment of the fovea is treated by either delimiting laser or direct
      treatment of focal leaks, depending on the distance of the lesion from the
      foveola. Choroidal hemangiomas are treated by light to medium photocoagulation
      over the tumor surface to create chorioretinal adhesion and reattachment of the
      retina. A small retinoblastoma is best treated by surrounding the tumor with
      heavy laser to destroy its blood supply without treating the lesion directly.
      Retinal capillary hemangioma can be treated by heavy direct laser application to
      the tumor, or by obliterating first the feeding artery and later the draining
      vein. CONCLUSION: Laser photocoagulation is an acceptable therapeutic option for
      selected benign and malignant intraocular tumors, and its role in the overall
      management of patients with intraocular tumors is expanding.

PMID- 7817025
TI  - The use of perfluoro-octane in the management of giant retinal tears without
      proliferative vitreoretinopathy.
AB  - PURPOSE: A technique for managing giant retinal tears without proliferative
      vitreoretinopathy (PVR) is presented, and visual outcome, anatomic reattachment,
      and postoperative complications are discussed. METHODS: A total of 25 consecutive
      cases of retinal detachment from giant retinal tears in eyes without PVR that had
      not previously undergone surgery were reviewed. A surgical technique combining
      pars plana vitrectomy, perfluoro-octane, and fluid-gas exchange was used. Scleral
      buckling was performed in 23 (92%) of 25 eyes, and pars plana lensectomy was
      performed in 11 (69%) of the 16 phakic eyes. A minimum follow-up period of 6
      months was documented in each case. RESULTS: Of the 25 eyes, redetachment
      occurred in 3 (12%) after the initial procedure, and further surgery was
      necessary to successfully reattach the retina. A total of 9 secondary procedures
      were performed in 7 (28%) of the 25 eyes. Final retinal reattachment was achieved
      in all 25 eyes. Final Snellen visual acuity was 20/80 or better in 18 (72%)
      patients and 20/200 or better in 21 (84%) patients. CONCLUSION: The anatomic and
      visual results of this method of surgical treatment of giant retinal tears
      without PVR compare favorably to those achieved with techniques that use a
      nonbuckling approach, but with reduced ocular morbidity.

PMID- 7817026
TI  - The vitreous in retinal arterial occlusions.
AB  - PURPOSE: To investigate whether retinal arterial occlusion induces posterior
      vitreous detachment (PVD). METHODS: Vitreous condition was studied
      retrospectively and examined on biomicroscopy in 52 eyes with retinal arterial
      occlusion; 50 fellow eyes served as controls. RESULTS: Of 52 eyes with retinal
      arterial occlusion 27 (52%) had PVD; 25 (50%) of the 50 control eyes had PVD.
      There was no significant difference between the two groups in prevalence of PVD.
      Of the 41 patients observed for more than 1 year, PVD developed in 2 (5%)
      patients from each group. CONCLUSION: Our findings strongly suggest that retinal
      arterial occlusion does not influence the development of PVD clinically.

PMID- 7817027
TI  - Scleral buckling for retinal detachment. Predictors for anatomic failure.
AB  - PURPOSE: The influence of various preoperative, intraoperative, and postoperative
      factors on retinal reattachment after scleral buckling was examined. METHODS: A
      study of 601 eyes of 577 consecutive patients who underwent conventional scleral
      buckling procedures was conducted. Multiple logistic regression analysis was used
      to determine the independent influence of each variable on anatomic failure.
      RESULTS: Anatomic reattachment of the retina was achieved in 86% of eyes after a
      single procedure, and in 90% of eyes after a second surgical procedure, with a
      mean follow-up period of 5.27 months (range, 2-29 months). Factors predictive of
      poor anatomic success (P < 0.05) included preoperative choroidal detachment and
      significant vitreous opacification; circumferential buckle extent of more than
      two quadrants and intravitreal injection of air or fluid intraoperatively; and
      postoperative occurrence of sterile vitritis. CONCLUSION: Breakdown of the blood
      retinal barrier leading to cellular migration and proliferation is considered to
      be predictive of anatomic failure after scleral buckling procedures.

PMID- 7817028
TI  - Drainage of subretinal fluid in retinal detachment surgery with the El-Mofty
      insulated diathermy electrode.
AB  - PURPOSE: A technique that uses the El-Mofty/Schepens diathermy tip (MIRA, Inc.)
      to effect drainage of subretinal fluid during scleral buckling surgery is
      described. The efficacy of this drainage technique and its complication rate in a
      series of consecutive patients is discussed. METHODS: The study included all of
      the scleral buckling procedures performed at the Retina Service for retinal
      detachments in which this technique was used. The El-Mofty/Schepens diathermy tip
      was first used to cauterize the choroid at the drainage site at low power, thus
      rendering it avascular, and then at higher power, to cause vaporization of the
      choroid, and allow spontaneous drainage of subretinal fluid. The success rate and
      all intraoperative and postoperative complications were recorded. RESULTS: This
      technique achieved successful spontaneous drainage in 53 (82.8%) of 64
      consecutive cases. Complications that are occasionally associated with the
      drainage of subretinal fluid, including iatrogenic retinal holes, choroidal
      hemorrhage, and retinal incarceration in the sclerotomy site, were not seen in
      any of the cases. CONCLUSION: This method provides a simple and safe technique
      for the drainage of subretinal fluid that obviates the need to directly perforate
      the choroid.

PMID- 7817029
TI  - External argon laser choroidotomy versus needle drainage technique in primary
      scleral buckle procedures. A prospective randomized study.
AB  - PURPOSE: To compare the rates of intraoperative and postoperative complications
      of external argon laser choroidotomy and needle drainage techniques during
      scleral buckle procedures for primary retinal detachment. METHODS: A group of 175
      patients undergoing scleral buckling for primary retinal detachment was randomly
      assigned to undergo either external argon laser choroidotomy or needle drainage.
      Complications associated with drainage of subretinal fluid were categorized as
      retinal break, retinal incarceration, or hemorrhage (dot, < or = 1 disc diameter
      [DD], or > 1 DD), and recorded during surgery and 24 hours after surgery.
      RESULTS: In the group that underwent laser choroidotomy, 12 (13%) of 92 patients
      had complications, including 4 dot hemorrhages, 3 hemorrhages 1 DD or smaller, 3
      hemorrhages larger than 1 DD, 1 retinal incarceration, and 1 suprachoroidal
      hemorrhage. In the group that underwent needle drainage, 13 (16%) of 81 patients
      had complications, including 3 dot hemorrhages, 4 hemorrhages 1 DD or smaller, 5
      hemorrhages larger than 1 DD, and 1 suprachoroidal hemorrhage. No significant
      difference was noted between the two groups in the incidence of complications (P
      = 0.657). CONCLUSION: External argon laser choroidotomy and needle choroidotomy
      are comparable, safe, and effective ways to drain subretinal fluid during scleral
      buckle surgery.

PMID- 7817030
TI  - Intraocular gas and low-altitude air flight.
AB  - BACKGROUND: Air travel has been contraindicated for patients with intraocular gas
      on the basis of experimental studies, because of the risk of elevated intraocular
      pressure during atmospheric depressurization. METHODS: A clinical study of gas
      bubble volume and intraocular pressure rise during a low-altitude air flight was
      performed on a patient with a gas bubble volume of 65% after retinal detachment
      surgery. RESULTS: The flight was well tolerated, and the patient did not
      experience pain or decreased vision. The maximum altitude of the flight was
      3,000. Maximum intraocular pressure was 49 mmHg, with a baseline of 16 mmHg.
      Increases in intraocular pressure and bubble volume were instantaneous with
      changes in altitude. Implications for pressurized flight situations are
      discussed. CONCLUSION: Low-altitude air flight can be well tolerated by patients
      with intraocular gas, even with a relatively large vitreous cavity gas fill.
      Decisions about when to let patients with intraocular gas fly should be made on
      an case-to-case basis, depending on ocular factors and the planned flight
      characteristics.

PMID- 7817031
TI  - Cavernous hemangioma of the optic nerve.
AB  - BACKGROUND: Cavernous hemangioma of the retina and optic disc is a rare lesion
      that was first defined as a distinct entity by Gass in 1971. It is usually easily
      recognized by its characteristic appearance of saccular "grape-like" lesions. On
      fluorescein angiography, plasma-erythrocyte separation is seen. METHODS: Two
      patients with cavernous hemangioma of the optic nerve were examined over a period
      of 5 to 10 years. RESULTS: Although these tumors are usually considered to be
      static and not capable of growth, these two cases of cavernous hemangioma of the
      optic nerve showed documented growth. One case required vitrectomy for vitreous
      hemorrhage. CONCLUSION: Cavernous hemangioma of the optic disc can grow and can
      cause vitreous hemorrhage severe enough to require vitrectomy.

PMID- 7817032
TI  - Injuries induced by diffuse photodynamic action in retina and choroid of albino
      rats. Morphologic study of an experimental model.
AB  - BACKGROUND: The morphologic changes of the retina, choroid, and respective
      vasculatures in an experimental model of diffuse photothrombosis and photodynamic
      injury were studied. METHODS: After intravenous injection of rose bengal (40
      mg/kg), eyes of 21 albino rats were exposed to a light intensity of 15-17,000 ft
      cd for 2 to 15 minutes. Survival times ranged from 15 minutes to 6 days. The
      specimens were studied by light and electron microscopy. RESULTS: Photothrombosis
      of retinal and choroidal vessels was variable in extension and duration. Vascular
      lesions included vacuolation and sloughing off of endothelium, and necrosis and
      apoptosis of pericytes and smooth muscle cells. Retinal and choroidal injuries
      exhibited considerable regional and structural differences, such as predominance
      in the outer versus inner retina, or focal versus diffuse injury. CONCLUSION:
      Damage produced by this model was irregular in extent and character, due to
      several hard-to-control parameters. It was presumably due not only to ischemia
      but also to free radical chain reactions initiated by photodynamic action. This
      model may not be suitable for rapid quantitative assessment of ischemic retinal
      injury, but it provides opportunities for the investigation of pathophysiologic
      mechanisms.

PMID- 7817033
TI  - A new instrument for insertion and extraction of scleral plugs during pars plana
      vitrectomy.

PMID- 7817034
TI  - Scleral buckle leash.

PMID- 7817035
TI  - Laser photocoagulation and fluid-gas exchange for recurrent macular hole.

PMID- 7817036
TI  - Visual outcome in acute retinal necrosis.

PMID- 7817037
TI  - Neural regulation of bronchial blood flow.
AB  - The neural regulation of the bronchial vasculature differs from that of the
      general systemic circulation in that vasodilator reflexes play a major part in
      determining blood flow. These reflexes originate in the upper or lower airways,
      in carotid chemoreptors or in cardiac chemosensitive nerves; those arising in the
      lower airways are most potent and may increase bronchial blood flow several-fold
      and cause swelling of the airway mucosa. Lower airway reflexes have afferent and
      efferent pathways in the vagus nerves, the former including sensory C-fibers and
      rapidly adapting receptors, the latter involving both cholinergic and non
      cholinergic transmitters. In addition, neuropeptides released from the C-fiber
      terminals provide a local mechanism for vasodilation independent of central
      reflex control. This so-called axon-reflex plays the major part in bronchial
      vasodilation in rodents but makes only a small contribution in larger animals. In
      larger animals centrally-mediated reflexes and vagal vasodilator pathways appear
      more important. Nevertheless, local neural vasodilation may be important in
      airway disease; the factors that favor its operation in animals other than
      rodents deserve to be explored.

PMID- 7817038
TI  - Contractility and myosin heavy chain isoform patterns in developing tracheal
      muscle.
AB  - Changes in airway smooth muscle reactivity with development may be caused by
      either modification of the excitation-contraction coupling system or alteration
      of the contractile apparatus. The mechanism responsible for the reported changes
      in reactivity was addressed in this study by examining airway smooth muscle
      contractility and myosin heavy chain isoform patterns as a function of post
      neonatal development. Changes in length and force, in response to supramaximal
      electrical stimulation, were recorded simultaneously as functions of time for
      tracheal smooth muscle (TSM) strips from 8-week-old and 25-week-old male rabbits.
      Both the passive and active length-tension (L-T) curves as well as the force
      velocity (F-V) curves for the two age groups of rabbit TSM were not significantly
      different indicating no changes in contractility during post-neonatal development
      in rabbits. This conclusion is surprising in light of reports of myosin heavy
      chain (MHC) isoform shifts in porcine trachealis during comparable periods of
      development. Therefore, MHC isoform ratios were compared by sodium dodecyl
      sulfate-polyacrylimide gel electrophoresis for tracheal smooth muscle from male
      rabbits of 8 and 25 weeks of age. Unlike the reported MHC isoform shifts in the
      pig tracheal muscle, the rabbit trachealis showed no difference in MHC isoform
      ratios between the two age groups compared in this study. In conclusion, no
      changes occur in contractility or MHC isoform patterns during post-neonatal
      development of rabbit tracheal smooth muscle. Therefore, reported changes in
      airway muscle reactivity are likely due to changes in receptors or in second
      messenger systems rather than to changes in the contractile apparatus.

PMID- 7817039
TI  - The metabolic and ventilatory response to exercise in Tibetans born at low
      altitude.
AB  - The exercise response of 20 Tibetans (T) born and living in Kathmandu, Nepal
      (1300 m) was compared to that of 21 age- and sex-matched local lowlanders. The
      subjects carried out an incremental exercise protocol on a bicycle ergometer (30
      watt steps every 4 min) until exhaustion. The kinetics of readjustment of VO2
      measured as half time (t-on) upon a 90 watt constant load exercise was also
      determined. Breath-by-breath gas exchange, heart rate (HR) and blood lactate
      concentration ([La]) were measured at rest, at the end of each load and during
      recovery. The slope of the straight line relating VO2 to work load was 10.8
      ml.watt-1 in both groups which corresponds to a mechanical efficiency of 0.26
      (assuming a RQ of 0.89 and an energy equivalent of 20.9 kJ.L-1 O2). At submaximal
      loads T were characterized by higher VE (P < 0.05), VE.VO2(-1) (P < 0.01) and
      VCO2 levels (P < 0.001) than N. The found higher VE in T, resulting from a lower
      tidal volume coupled to a higher respiratory frequency, led to higher PETO2 (P <
      0.001) and SaO2 (P < 0.001) at all work levels. Absolute VO2max in the two
      investigated groups were 1977 +/- 72 (T) and 2095 +/- 80 (N) ml.min-1 (NS).
      Specific (i.e. per kg body weight) VO2max were identical (37.0 +/- 1.1 [T] vs.
      36.7 +/- 1.1 ml.kg-1.min-1 [N]). [La]max were 11.4 +/- 0.4 (T) vs. 12.3 +/- 0.4
      (N) mM (NS). [La] accumulation in blood as a function of workload and its rate of
      disappearance during recovery were similar. t-on at 90 watt was 30.7 +/- 2.4 sec
      in T and 28.9 +/- 2.3 sec in N (NS). The corresponding average contracted O2
      deficit were 971 ml for T and 994 ml for N (NS). In conclusion, Tibetans born at
      low altitude do not seem to differ from lowlanders with regard to their metabolic
      response whereas their ventilatory response to exercise is greater.

PMID- 7817040
TI  - Carbonic anhydrase and CO2 chemoreception in the pulmonate snail Helix aspersa.
AB  - We have studied the effects of carbonic anhydrase inhibition on the hypercapnic
      ventilatory response of the pulmonate snail, Helix aspersa, in an isolated brain
      pneumostome preparation. We found that the cell permeant carbonic anhydrase
      inhibitor, acetazolamide (ACTZ), increased pneumostomal opening and ventilation
      during normocapnia (2-3% CO2) and decreased the rate of pneumostomal response to
      step changes in CO2 (4.5%), but did not change the steady-state ventilatory
      response to elevated CO2 (4.5%) compared to the inactive ACTZ analogue, N2
      substituted 2-acetylamino-1,3,4-thiadiazole (Cl 13850). In contrast, the cell
      impermeant carbonic anhydrase inhibitor, quartenary ammonium sulfonilamide (QAS),
      had no effect on the pneumostomal response to CO2 compared to Cl 13850. Using
      Hansson's histochemical technique to stain for carbonic anhydrase activity, we
      identified a small number of neurons in the subesophageal ganglia that exhibited
      carbonic anhydrase activity. Some of these cells were in the region of CO2
      sensitivity. In conclusion, carbonic anhydrase inhibition slows the ventilatory
      response to rapid changes in CO2, but does not affect the intrinsic ability of H.
      aspersa to respond to CO2. The ventilatory effects of carbonic anhydrase
      inhibition may be attributed to the intracellular actions of the carbonic
      anhydrase enzyme.

PMID- 7817041
TI  - Respiratory action of the canine deep pectoral muscles.
AB  - The potential respiratory action of the pectoral muscles is unclear. We studied
      the effect of electrically stimulated contraction of the deep pectoral muscles on
      intrathoracic pressure (Pes) and lung volume in 15 supine anesthetized dogs.
      Changes in Pes and lung volume were also compared with the forelimbs held at the
      animal's side and elevated 45 degrees to the horizontal plane to alter the
      mechanical advantage of the deep pectoral muscles. In all animals, bilateral
      supra-maximal stimulation of the deep pectorals produced negative changes in Pes
      (-5.9 +/- 0.6 cmH2O) and inspiratory changes in lung volume (324 +/- 44 ml) with
      the forelimbs elevated. Conversely, in all animals, stimulation of the deep
      pectorals with the forelimbs at the side produced positive changes in Pes (+ 2.6
      +/- 0.2 cmH2O, Plt;0.001) and expiratory changes in lung volume (-113 +/- 16 ml,
      Plt;0.001). Furthermore, forelimb elevation increased deep pectoral muscle fiber
      length (mean change 39.9 +/- 7.5% of resting length, Plt;0.001) and reoriented
      fiber alignment with the rib cage more rostrally. These data indicate that the
      pectoral muscles exert a respiratory action on the rib cage. Moreover, forelimb
      posture affects the direction (i.e., inspiratory vs. expiratory) and magnitude of
      pectoral muscle mechanical action by altering muscle fiber alignment and
      precontraction length.

PMID- 7817042
TI  - Contribution of viscoelastic stress to the rate-dependence of pulmonary dynamic
      elastance.
AB  - To further characterize the contribution of the stresses accumulated during
      inflation in viscoelastic elements of the lungs to the rate-dependence of
      pulmonary dynamic elastance, we analyzed the changes in the pressures measured at
      the airway opening and in subpleural air spaces during airway occlusions
      performed at constant inflation rates of 5, 10, 20, and 40 ml/(kg sec) in 13
      anesthetized piglets (mean age = 7 days). The analysis was repeated after saline
      lavage of the lungs and during intravenous infusion of histamine in 7 and 4 of
      the piglets, respectively. Viscoelastic stresses dissipated as stress relaxation
      were solely responsible for the differences between dynamic and static elastance
      before and after lung lavage and for more than 40% of this difference during
      histamine infusion (the remainder probably being caused by ventilation
      inequalities). The viscoelastic contribution to dynamic elastance increased by
      more than two-fold after lung lavage and was independent of inflation rate and
      only minimally dependent upon inflation volume. Our results demonstrate that
      viscoelastic stresses are primarily responsible for the dynamic stiffening of
      piglet lungs at low rates of inflation. They also support the notion that
      viscoelastic and elastic stresses are coupled as the lungs inflate.

PMID- 7817043
TI  - Blood O2 transport in newborn and adult of a very small marsupial (Sminthopsis
      crassicaudata).
AB  - Blood O2 transport and hemoglobin types have been studied in a Dasyurid marsupial
      (Sminthopsis crassicaudata) at the neonatal (10-20 mg) and adult (16 g) stages,
      and in part of the transition period. In neonates the blood was embryonic in type
      with erythrocytes nucleated and containing two Hb types both different from adult
      Hb. The oxygen equilibrium curves (OECs) at day 1 had a P50 of 38 mmHg at 36
      degrees C and PCO2 = 43 mmHg. This is lower than in other neonatal marsupials,
      but higher than in fetal or neonatal eutherian mammals. Adult P50 under the same
      conditions were higher (59 mmHg), the normal relationship in viviparous animals.
      Hill plots of neonatal OECs showed a sharp upward bend at about 50% saturation.
      As in other embryonic and neonatal marsupials, in the upper part of the plot nH
      was greater than 4. This indicates aggregation of Hb tetramers. The Bohr effect
      of neonatal blood at higher PCO2 values (43-71 mmHg PCO2) was zero. The special
      features of neonatal blood had largely disappeared by day 6.

PMID- 7817044
TI  - Role of pulmonary intravascular macrophages in anti-platelet serum-induced
      pulmonary hypertension in sheep.
AB  - It has been reported that an injection of anti-sheep platelet serum (AsPS)
      induces transient pulmonary hypertension in sheep, but the mechanism by which
      this occurs has not been well explained. To examine the hypothesis that pulmonary
      intravascular macrophages (PIMs) are involved in this phenomenon, we investigated
      the morphological features of PIMs from sheep that received three different kinds
      of AsPS injections. The pulmonary arterial pressure response was examined not
      only in sheep that have many PIMs in the lung and had received AsPS, but also in
      rats that reportedly have few PIMs and had received an injection of anti-rat
      platelet serum. The pulmonary arterial pressure responses of the two species were
      quite different in quality and quantity. In sheep whose pressure response was
      definitely positive in association with production of thromboxane in the
      pulmonary circulation, PIMs were found by fluorescent microscopy and electron
      microscopy to phagocytize aggregated platelets that bound AsPS. These results
      suggest that PIMs significantly contribute to AsPS-induced transient pulmonary
      hypertension in sheep.

PMID- 7817045
TI  - Ontogeny of the O2-sensitive pathway in medulla oblongata of postnatal rat.
AB  - Fos protein, the product of the immediate early gene c-fos, has been used as a
      metabolic marker to map the O2 chemosensory pathway activated by hypoxia in the
      adult rat (Erickson and Millhorn, Brain Res. 567: 11-24, 1991). The current study
      provides evidence that the O2 chemoreceptor pathway develops during the first
      postnatal month. Rats at postnatal ages (P) 3, 7, 10, 14, 21, and 28 days were
      exposed for 3 h to 21% (control) or 10% (hypoxia) O2. Pups were transcardially
      fixed, brain stems were frozen, sectioned, then reacted with Fos primary
      antibody, a secondary antibody, avidin-biotin peroxidase, then Ni-DAB as
      chromogen. Cells showing Fos-like immunoreactivity (Fos-LI) under control and
      hypoxic conditions were counted in the nucleus tractus solitarii (NTS) and the
      ventrolateral medulla (VLM). In both areas there was initially a low basal level
      of Fos-LI, a peak at P10 and a decline to P28. At all ages there was a
      significant increase in the number of Fos-LI cells in pups exposed to hypoxia.
      The high basal level of Fos expression at P10 and the high induced level at P14
      may correlate with periods of terminal differentiation and maximum
      synaptogenesis, respectively.

PMID- 7817046
TI  - Ventilatory responses to acute and chronic hypoxic hypercapnia in the ground
      squirrel.
AB  - Golden-mantled ground squirrels exhibited a strong hypoxic ventilatory response
      but a blunted hypercapnic ventilatory response and showed no interactive effects
      when both stimuli were presented together. They exhibited a resting hypoxic
      ventilatory drive which was eliminated by carotid body denervation. Carotid
      denervation also shifted the threshold of the hypoxic ventilatory response but
      had no effect on the slope of either the hypoxic or hypercapnic ventilatory
      responses. Chronic exposure (2-12 months) to hypoxic-hypercapnic conditions (16%
      O2, 4% CO2) resulted in a sustained increase in ventilation. Initial increases in
      both tidal volume (VT) and breathing frequency (fR) were followed by a subsequent
      further increase in VT and concomitant decrease in fR (acclimation) which had
      little overall effect on ventilation (VE) but further increased calculated
      alveolar ventilation (VA). Respiratory sensitivity to hypoxia and hypercapnia
      were unaltered under these conditions. On acute return to breathing room air, VE
      remained elevated (approximately 35%) compared to control animals suggesting that
      deacclimation takes time. Carotid body denervation in these animals had similar
      effects to those seen in control animals suggesting that acclimation did not
      involve changes in carotid body input.

PMID- 7817047
TI  - Limited capacity for glyconeogenesis from alanine by diaphragm muscle.
AB  - The mammalian diaphragm (Dia) is a unique skeletal muscle because of its chronic
      contractile activity. Chronically active muscles have higher capacities for
      glycogen synthesis from lactate and glucose. In this study, the contribution of
      alanine to glycogen synthesis in the predominantly fast-twitch mouse Dia was
      determined. Chronically active fast- and slow-twitch muscles from dy2J/dy2J
      pseudomyotonic mice were also analyzed. Alanine aminotransferase (AlaAT) activity
      was significantly (P < 0.05) greater in Dia and chronically active gastrocnemius
      muscle (Gast) than control Gast. 14C-label incorporation into glycogen following
      in vivo injection of 14C-alanine, was significantly higher in Dia and chronically
      active Gast than control Gast. A direct incorporation of 14C from 14C-alanine
      into glycogen is also observed in vitro. The incorporation rate shows a linear
      concentration dependent relationship and a pH optimum of 6.3. Insulin had no
      effect on glycogen synthesis from alanine by Dia in vitro. The extensor digitorum
      longus muscle (EDL) and chronically active EDL and soleus muscle (Sol) had higher
      rates of glycogen synthesis from alanine than control Sol and Dia. The oxidation
      of alanine to CO2 was the primary route for alanine metabolism by the Dia. These
      results demonstrate that the Dia can synthesize glycogen from alanine, but only
      at low rates.

PMID- 7817048
TI  - Ventilation-perfusion inequality and diffusion impairment in acutely injured
      lungs.
AB  - To assess the significant role of diffusion impairment and its unequal
      distribution in acutely injured lungs with alveolar flooding, oleic acid was
      intravenously injected into twenty-five mongrel dogs. The animals were divided
      into two groups, A and B. 0.1% CO in air was delivered, as an inspired gas, to
      the animals of group A. Simultaneously, saline containing a trace amount of six
      foreign inert gases was infused through a peripheral vein. While allowing the
      animals in group B to breathe air, saline containing ethylene, acetylene and
      freon 22 was infused. After injection of oleic acid, group A revealed increase in
      intrapulmonary shunt accompanied by a marked broadening of ventilation-perfusion
      (VA/Q) and diffusing capacity-perfusion (G/Q) distributions. A considerable
      amount of total cardiac output was received by the lung areas with low G/Q ratios
      where significant diffusion limitation was predicted to occur. Group B showed
      that excretion of freon 22 (gas with lower diffusivity) in injured lungs was
      considerably distorted as compared to those of ethylene and acetylene (gases with
      higher diffusivities), again ascertaining the importance of diffusion limitation
      in lungs with exudate in alveolar regions.

PMID- 7817049
TI  - Segmental pulmonary vascular resistances during oleic acid lung injury in
      rabbits.
AB  - We studied in isolated rabbit lungs the effects of oleic acid (OA) injury on the
      segmental distribution of vascular resistance. Vascular occlusion pressures were
      measured in control and OA-injured preparations over 90 min. Capillary filtration
      coefficient KF,C increased from 0.61 (+/- 0.10) to 0.91 (+/- 0.14) g.min-1.mmHg
      1.(100 g)-1 in OA-injured lungs whereas it remained constant in control lungs.
      Total pulmonary vascular resistance changed little in both control and OA-injured
      lungs. OA injury resulted in a 15% increase of the double occlusion capillary
      pressure. In addition, the contribution of the microvascular to the total
      vascular resistance rose from 8% to 22%. The increase in microvascular resistance
      was significant 15 min after OA on the arteriolar side and became significant 30
      min later on the venular side. Oleic acid injury does not change the total
      pulmonary vascular resistance but alters the distribution of segmental
      resistances in the isolated rabbit lung, thereby contributing to the accumulation
      of lung water in this model of low pressure permeability edema.

PMID- 7817050
TI  - A diameter-based reconstruction of the branching pattern of the human bronchial
      tree. Part I. Description and application.
AB  - We propose an analysis of the branching pattern of the conducting airways of the
      human bronchial tree, based on classifying airways by diameter rather than by
      some essentially topological measure of their position in the whole lung. A
      diameter-based statistical reconstruction technique is applied to the partial
      measurements of airway dimensions made by Raabe et al. (1976), to quantify some
      aspects of bronchial geometry likely to influence transport processes in the
      lung. We give predictions for the total number of airways with each diameter, and
      for the partitioning of the total bronchial wall area and airway volume between
      airways of different diameters. We also consider the variability of the lengths
      of different pathways through the bronchial tree, and using a simple model for
      the distribution of air flow in the lung, we predict how the average flow
      velocity depends on airway diameter. Comparison of these results with equivalent
      predictions derived from Weibel's symmetrical lung model shows qualitative
      differences, which probably result from Weibel's use of extrapolation techniques
      to compensate for the lack of data on smaller conducting airways. Comparison with
      the predictions of Horsfield and Cumming's asymmetrical lung model shows
      generally good agreement, although there are significant differences relating to
      the asymmetry of bifurcations and to the diameter-dependence of the flow velocity
      in the smallest conducting airways.

PMID- 7817051
TI  - A diameter-based reconstruction of the branching pattern of the human bronchial
      tree. Part II. Mathematical formulation.
AB  - In this paper we present the mathematical details of the diameter-based
      reconstruction technique used in the companion paper (Phillips et al., 1994 -
      referred to below as Part I) to analyse the morphometric data of Raabe et al.
      (1976) on the human bronchial tree. In the first section we outline the technique
      as applied to the incomplete set of measurements in order to estimate properties
      of the bronchial tree as a whole; in the second section we consider what form
      these properties would take if the bronchial tree were geometrically self
      similar, as has often been assumed to be approximately the case.

PMID- 7817052
TI  - Measurement of oxygen uptake in newborn infants during assisted and spontaneous
      ventilation.
AB  - Measurements of oxygen uptake (VO2) and CO2 output (VCO2) are useful in
      critically ill patients. However, VO2 is not routinely measured in intensive care
      during mechanical ventilation (MV) especially in premature newborns. The present
      study describes a new method of measuring VO2 and VCO2 using a double open
      circuit which accounts for gas leaks around the uncuffed tracheal tube. The
      accuracy of the method was assessed with N2 and CO2 infusion. In case of leaks,
      VO2 and VCO2 measurement was significantly underestimated by the simple circuit
      method. This underestimation was not present with double circuit method. Five
      preterm newborns were studied. VO2 and VCO2 using the double open circuit were
      compared with the classic simple circuit. During MV, the mean underestimation
      assessed by the difference between simple and double circuit measurement was -12%
      (range from 0 to -29%) for VO2 and -14% (range 0 to -26%) for VCO2.

PMID- 7817053
TI  - [How I treat... adaptation disorder with anxiety].

PMID- 7817054
TI  - [Plague. A medieval resurgence?].

PMID- 7817055
TI  - [Topical application of antimicrobial agents in periodontics. Current status of
      the problem].

PMID- 7817056
TI  - [Current aspects of the main allergic ocular disorders].

PMID- 7817057
TI  - [Human pheromones: animal trace or unrecognized reality?].

PMID- 7817058
TI  - [Daily life of the country doctor in the 19th century].

PMID- 7817059
TI  - [2 new mediator "exons", the Nobel Prize in Medicine, R.J. Roberts and P.A.
      Sharp].

PMID- 7817060
TI  - [Drug of the month. fosinopril (Fosinil)].

PMID- 7817061
TI  - Maternal exercise during pregnancy.
AB  - Recent evidence resulting in revised ACOG Guidelines will allow physicians more
      latitude with their advice for women wishing to exercise during pregnancy.
      However, there is an increased responsibility for both mother-to-be and her
      physician to design an individualised activity programme to meet specific goals.
      The recommendation should continue to be that any woman who chooses to begin, or
      maintain an exercise routine during pregnancy should do so in consultation and
      proactive partnership with her obstetrician.

PMID- 7817063
TI  - Evaluation of the ergogenic properties of ginseng.
AB  - Ginseng has been used for several thousand years in the Orient as a tonic,
      prophylactic agent and 'restorative'. However, its efficacy has been established
      primarily through clinical experience as opposed to scientific verification of
      its pharmacological effects. Ginseng has been used by athletes as an ergogenic
      aid for many years, but there is an absence of compelling research evidence in
      support of its use for this purpose. Indeed, most of the support favouring the
      use of ginseng to enhance physical performance is of a testimonial nature. While
      studies with animals show that ginseng or its active components may prolong
      survival to physical or chemical stress, there is, generally, a lack of
      controlled research demonstrating the ability of ginseng to improve or prolong
      performance in fatigued humans.

PMID- 7817062
TI  - Exercise and diet in the prevention and control of the metabolic syndrome.

PMID- 7817065
TI  - Creatine in humans with special reference to creatine supplementation.
AB  - Since the discovery of creatine in 1832, it has fascinated scientists with its
      central role in skeletal muscle metabolism. In humans, over 95% of the total
      creatine (Crtot) content is located in skeletal muscle, of which approximately a
      third is in its free (Crf) form. The remainder is present in a phosphorylated
      (Crphos) form. Crf and Crphos levels in skeletal muscle are subject to individual
      variations and are influenced by factors such as muscle fibre type, age and
      disease, but not apparently by training or gender. Daily turnover of creatine to
      creatinine for a 70kg male has been estimated to be around 2g. Part of this
      turnover can be replaced through exogenous sources of creatine in foods,
      especially meat and fish. The remainder is derived via endogenous synthesis from
      the precursors arginine, glycine and methionine. A century ago, studies with
      creatine feeding concluded that some of the ingested creatine was retained in the
      body. Subsequent studies have shown that both Crf and Crphos levels in skeletal
      muscle can be increased, and performance of high intensity intermittent exercise
      enhanced, following a period of creatine supplementation. However, neither
      endurance exercise performance nor maximal oxygen uptake appears to be enhanced.
      No adverse effects have been identified with short term creatine feeding.
      Creatine supplementation has been used in the treatment of diseases where
      creatine synthesis is inhibited.

PMID- 7817067
TI  - [Genetic aspects of fetal hydrops and cystic hygroma].

PMID- 7817064
TI  - Effects of bodyweight reduction on sports performance.
AB  - Athletes reduce bodyweight for several reasons: to compete in a lower weight
      class; to improve aesthetic appearance; or to increase physical performance.
      Rapid bodyweight reduction (dehydration in 12 to 96 hours), typically with fluid
      restriction and increased exercise, is used by athletes competing in weight-class
      events. Gradual bodyweight reduction (over > 1 week) is usually achieved by
      cutting energy intake to 75 to 130 kJ/kg/day. An intake of 100 kJ/kg/day results
      in a weekly bodyweight loss of roughly 1kg. Aerobic endurance capacity decreases
      after rapid bodyweight reduction, but might increase after gradual bodyweight
      reduction. Maximal oxygen uptake (VO2max) measured as L/min is unchanged or
      decreased after bodyweight loss, but VO2max measured as ml/kg/min may increase
      after gradual bodyweight reduction. Anaerobic performance and muscle strength are
      typically decreased after rapid bodyweight reduction with or without 1 to 3 hours
      rehydration. When tested after 5 to 24 hours of rehydration, performance is
      maintained at euhydrated levels. A high carbohydrate diet during bodyweight loss
      may help in maintaining performance. Anaerobic performance is not affected and
      strength can increase after gradual bodyweight reduction. Reductions in plasma
      volume, muscle glycogen content and the buffer capacity of the blood explain
      decreased performance after rapid bodyweight reduction. During gradual bodyweight
      loss, slow glycogen resynthesis after training, loss of muscle protein and stress
      fractures (caused by endocrinological disorders) may affect performance.
      Athletes' bodyweight goals should be individualised rather than by comparing with
      other athletes. If the time between weigh-in and competition is < 5 hours, rapid
      bodyweight reduction should not exceed 4% of bodyweight. If the time interval is
      longer, a bodyweight reduction < or = 8% might be acceptable. A moderate-energy
      (100 to 120 kJ/kg/day) and high-carbohydrate (60 to 70% of total energy intake)
      diet is recommended. Gradual bodyweight reduction may be 0.5 to 1.5 kg/week.
      Energy intake should be 80 to 120 kJ/kg/day, with a high carbohydrate (60 to 70%)
      and a low fat (15 to 25%) content.

PMID- 7817068
TI  - [Prenatal diagnosis of genetic diseases: Lausanne experience 1989-1993].

PMID- 7817066
TI  - The role of imaging in the diagnosis of postural disorders related to low back
      pain.
AB  - The function of the spine in humans is support of the body in an upright
      position, whilst defying gravity, conserving energy and permitting purposeful
      movement. Low back pain may either be caused by or result in postural disorders.
      It is an important cause of lost workdays in the industrialised world, with
      accompanying social and economic implications, and is a common and disabling
      problem in many sports. Increased awareness of the potential benefits of
      exercise, together with a change in attitudes in professional sport (placing
      greater pressure upon individuals to achieve more spectacular results), have
      resulted in increased pressure on medical services. This article reviews the
      examination protocols and clinical applications of the diagnostic imaging
      modalities available for the evaluation and diagnosis of postural disorders
      related to low back pain. Conventional radiography continues to be of value in
      demonstrating skeletal relationships and quantifying spinal kinematics. Computed
      tomography (CT) is widely available and highly accurate in the evaluation of disc
      herniation and spinal stenosis. Magnetic resonance imaging (MRI) demonstrates
      discs and the spinal cord with superb morphological accuracy, is painless and
      noninvasive, and has no known adverse effects or morbidity. It is the most
      accurate and sensitive modality for diagnosis of subtle occult changes in low
      back pains in patients where early preventative measures can be adopted to avoid
      further damage.

PMID- 7817069
TI  - [Epidemiological and clinical development of HIV+ patients followed by the
      Lausanne University Hospital Center from 1982 to 1992].

PMID- 7817070
TI  - [The approach of the letterbox: a model of sex education in a traditional
      society].
AB  - The present article describes a new approach for imparting sex-education to
      adolescents in a conservative and orthodox society like India. The initial
      community resistance to sex education was overcome by conducting a survey on the
      sex behaviour of adolescents. Contrary to popular belief and notions, the survey
      proved that some adolescents are sexually active and that they are not adequately
      equipped to prevent and protect themselves against sexually transmitted diseases,
      AIDS and unwanted pregnancies. The new model is essentially based on the
      team/group approach and utilises a group of trained and motivated teachers in
      schools to impart sex education to a group of students. The students' response to
      this approach has been heartening and encouraging.

PMID- 7817072
TI  - [The Community Health Certificate: an original experience at the medical faculty
      of Geneva].

PMID- 7817071
TI  - [Primary cardiac lymphoma with obstructive cardiac insufficiency].
AB  - A 80 year old man, in general good health, presented with a rapidly progressive
      congestive heart failure, without response to treatment. At echocardiography,
      there were masses in the right atrium and ventricle. The patient deceased two
      months after the first clinical manifestations. At autopsy, we found a massive
      right-sided atrio-ventricular infiltration by a malignant non-Hodgkin's lymphoma
      of centroblastic type, causing a subtotal obstruction of the tricuspid and
      pulmonary valves. We observed also four intestinal metastases without other
      manifestations of lymphoma.

PMID- 7817073
TI  - [Open injuries of the hand at the general practitioner's office].

PMID- 7817074
TI  - [The Louis Megevand Fund].

PMID- 7817075
TI  - [Home delivery].
AB  - Home delivery, although unconventional, has not totally disappeared. It sometimes
      results from the desire to "demedicalise" an event deemed natural and is
      sometimes the consequence of government policy and hence approved by medical
      authorities. This is the unique situation of Holland, where a highly efficient
      home delivery system has been created, with the possibility of transfer of the
      mother at any time to rapidly available emergency medical teams. In fact the
      large majority of home deliveries are accidental, unprepared and take place in
      the absence of any medical or paramedical assistance. All available studies show
      that perinatal and maternal morbidity associated with these accidental deliveries
      is greater than that of hospital deliveries, and this despite the setting up of
      emergency services responding as soon as a distress call is received. Home
      delivery should remain the exception at present since it is unable to guarantee a
      birth as undangerous as possible.

PMID- 7817077
TI  - [Complications of delivery].
AB  - Complications of delivery are dominated by the problem of obstetric hemorrhages.
      Minor complications are common, concerning about 20% of all labors, while serious
      complications are rare: of the order of 0.1%. Their peculiarity lies in their
      association with blood coagulation disturbances of multifactorial origin.
      Treatment requires close cooperation between the anesthesiologist/intensive care
      specialist and the obstetrician when management decisions are made. Trials of
      medical and obstetric measures should not lead to any delay when deciding that
      laparatomy is required to ensure hemostasis. Hesitation most often compromises
      the chances of success of conservative surgical treatment by selective ligations
      and forces hysterectomy.

PMID- 7817076
TI  - [Serious forms of arterial pregnancy-related hypertension].
AB  - Pregnancy related hypertension is the primary cause of perinatal mortality and
      morbidity. Its incidence is of the order of 10%. Serious forms, which account for
      10% of all cases of pre-eclamptic toxemia, remain a potential cause of maternal
      mortality and morbidity. Retroplacental hematoma, neurological problems dominated
      by eclampsia, coagulation disorders, Hellp syndrome, and hepatic, pulmonary,
      cardiac and renal problems are the essential complications of this pathology.
      They are described separately here, but are often associated. These potential
      complications require the careful evaluation of the severity of materno-fetal
      status. The management of these patients requires cooperation between the
      anesthetist/intensive care specialist, obstetrician and pediatrician. Such
      teamwork results in appropriate management for each individual patient. The
      various types of treatment are reviewed. Maternal and fetal mortality and
      morbidity could nevertheless be reduced by the early and careful management of
      high-risk patients, in particular by the prescription of low doses of aspirin and
      by careful clinical, ultrasound and velocimetric monitoring.

PMID- 7817078
TI  - [Ovarian hyperstimulation syndrome in medically assisted reproduction].
AB  - Ovarian hyperstimulation syndrome (OHS) is the most serious complication of
      ovulation induction, particularly in in vitro fertilization. It is a potentially
      life-threatening situation. Its pathophysiology is poorly understood. This
      syndrome is explained by a sudden increase in capillary permeability which
      results in a rapid fluid shift from the intravascular space into a third space
      leading to haemodynamic changes. In its most severe forms. OHS is characterized
      by multicystic ovarian enlargement, hemoconcentration, hypovolemia, oliguria,
      third space accumulation of fluid in the form of ascites and pleural effusion,
      renal failure, thrombotic disorders. Mild and the most of moderate forms of OHS
      usually do not require any active form of therapy. Severe OHS requires
      hospitalization, correction of fluid and electrolyte imbalance, prevention of
      thromboembolism, aspiration of the ascites and pleural effusion causing
      respiratory discomfort and dyspnea. Surgical interventions are exceptionally
      indicated and reserved for ovarian or rupture of ovarian cyst. Although severe
      OHS may not be completely avoided, early recognition of high-risk factors,
      judicious monitoring of ovulation induction (plasma estradiol levels and
      ultrasonography), and, perhaps in future, substitution of hCG for triggering
      ovulation should reduce the incidence of this iatrogenic syndrome.

PMID- 7817079
TI  - [Risks of prolonged tocolysis].
AB  - Premature delivery menace is still a major issue in obstetrics. It concerns 4 to
      5% of the pregnancies. Being responsible of an important fetal morbidity, it
      implies the use of a rapid and efficient treatment. This treatment uses
      progestins, prostaglandins inhibitors and beta-mimetics. The more efficient these
      medicines are, the more dangerous is their use so that their prescription must be
      weighted thoroughly, after setting apart the absolute counter-indications. Since
      they may cause severe accidents, especially cardio-vascular ones as for the beta
      mimetics, this implies an indespinsable medical follow up during their use. This
      article, using a review of the literature, enumerates the various pharmacological
      families prescribed for the treatment of the premature delivery menace. For each,
      the pharmacological effects, the tolerance, the side effects and the accidents
      are detailed. The modalities of their prescription as well as the necessary
      medical follow up are given. Taking into considerations these elementary rules of
      prescription enhances the chances of lowering down at most the risks related to
      the use of these treatments.

PMID- 7817081
TI  - [Albert Netter workshop, Paris, February 1994].

PMID- 7817080
TI  - [Recommendations of the French Society of Mammography and Breast Pathology on
      quality criteria in mass screening for breast cancer in France].

PMID- 7817082
TI  - [Acute pelvic pain syndrome. Diagnostic and therapeutic approach in women].
AB  - Acute pelvic pain is a common syndrome in women and is an emergency. Management
      requires rapid diagnostic evaluation to enable immediate treatment. Blood tests
      (beta-HCG assay, etc.), bacteriological studies and pelvic ultrasonography may be
      required. Gynecological problems are the commonest etiology: ectopic pregnancy,
      miscarriage, PID. The possibility nevertheless remains of appendicitis, sigmoid
      diverticulitis, UTI or renal colic, all of which are medical or surgical
      emergencies.

PMID- 7817083
TI  - [Peculiarities of the emergency care in pregnant women].
AB  - Awareness of the physiological changes associated with pregnancy is essential for
      the management of patients during pregnancy. Cardiovascular status is
      characterised by hypervolemia and cardiac hyper-output with low resistance.
      Increased oxygen consumption and respiratory work result in an increased risk of
      hypoxia. Fetal well-being must also be taken into account. During
      cardiorespiratory arrest, aortocaval compression by the pregnant uterus may
      impair the efficacy of CPR and uterine displacement is a routine measure starting
      from 20 weeks after the LMP. The same factors are involved in hemorrhagic shock,
      justifying uterine displacement and the ensuring of optimal oxygen transport and
      utilisation.

PMID- 7817084
TI  - [Extrauterine pregnancy].
AB  - The pattern of ectopic pregnancy, defined by an ectopic site of the fertilised
      ovum, has changed in recent years in developed countries. It is only rarely
      responsible for maternal death in industrialised countries though the possibility
      remains (1/4000). However, it plays an increasing role in the pathophysiology of
      female infertility. In terms of epidemiology, the increase in its rate is linked
      to that of salpingitis and sexually transmitted diseases, and the sequelae of
      tubal surgery. Regarding symptomatology and prognosis, dramatic, life-threatening
      forms are in clear decline, because of the possibility of the early detection of
      pregnancy by sensitive and rapid assay of beta sub-unit human chorionic
      gonadotrophin (beta-hCG) and transvaginal ultrasonography. This enables
      conservative management regarding the tube, but is associated with the risk of
      recurrence. In terms of treatment, laparoscopic surgery is gradually taking the
      place of laparotomy. Such laparoscopic surgery must now be considered
      "theoretically" to be the reference treatment. Medical treatment methods using
      methotrexate are currently being evaluated and it is even possible in certain
      cases to suggest that no treatment is required.

PMID- 7817085
TI  - [Abdominal emergencies and pregnancy].
AB  - The authors report the principal abdominal surgical emergencies which may occur
      during pregnancy. Missed diagnosis of these acute abdomens forms the basis of
      their gravity in terms of both maternal and fetal prognosis.

PMID- 7817086
TI  - [Hemorrhage during the 3d trimester of pregnancy].
AB  - Bleeding during the final three months is a serious event. Mortality is very
      slight in developed countries but morbidity remains considerable. Fetal mortality
      and morbidity are notable, linked to resultant pathology or prematurity. Their
      existence requires hospitalisation in a department of gynecology/obstetrics, with
      a team including an obstetrician, anesthetist/intensive care specialist, and
      pediatrician. Bleeding is due to placental separation involving the inter-villous
      chamber (basal decidual hematoma) or the marginal region (marginal decidual
      hematoma). Precise diagnosis of refractory bleeding is essential and must be
      obtained simultaneously with treatment. Maternal and fetal prognosis can only be
      improved by early and appropriate management. The treatment of serious cases is
      based upon intensive therapy including the replacement of losses, the correction
      of possible hemostasis problems and fetal extraction. Delivery is a critical
      phase, with the risk of extremely heavy bleeding and decompensation. This stage
      of labour requires careful monitoring and intensive therapy without delay.

PMID- 7817087
TI  - [Breast cancer in young women. Does it have special diagnostic, therapeutic and
      prognostic factors?].

PMID- 7817088
TI  - [How to investigate menometrorrhagias at the time of menopause?].
AB  - Metromenorrhagia is common around the time of the menopause. Following a careful
      history and full gynecological examination, vaginal ultrasonography and
      hysteroscopy combined with biopsies enable the investigation of such genital
      bleeding. Vaginal ultrasonography can be used to visualise the uterine cavity and
      measure the thickness of the endometrium. The term atrophy is used if the latter
      is less than 5 mm. If, on the contrary, the endometrium is thick or if there is a
      more notable intracavitary lesion, hysteroscopy and the collection of biopsy
      material guided by it will provide the diagnosis.

PMID- 7817089
TI  - [Prevention of breast cancer by tamoxifen. The opinion of the French Society of
      Senology and Breast Pathology].

PMID- 7817090
TI  - [Prehospital care of injuries received in traffic accidents: the Brazilian
      experience].

PMID- 7817091
TI  - Scanning electron microscope study of the veins at the human esophago-gastric
      junction.
AB  - Cast of the mucosal and submucosal veins of the esophago-gastric junction were
      studied in five necropsy specimens by scanning electron microscopy to analyse
      some of the characteristics of their shape and surface. Two types of veins were
      described: 1) veins with circumscript, fusiform and/or ampullar bulges and
      relatively smooth surfaces; 2) veins with numerous, small bulges and blister
      shaped micro-dilatations. The role of these features is considered in the
      formation of esophageal varices.

PMID- 7817092
TI  - [Current status of "Split-liver" as a liver transplantation technique option:
      review of the literature].
AB  - The availability of donor organs is a critical factor that limits the use of
      orthotopic liver transplantation. Split-liver technique means by cutting the
      liver into two hemilivers one could implant the new reduced-livers in two
      recipients. The authors have extensively reviewed the literature and concluded
      that in spite of both greatest postoperative complications and mortality, this
      technique could be useful in both chronically waiting list patients and those
      with acute hepatic failure whom desperately need a new organ.

PMID- 7817093
TI  - [Reactive arthritis and its etiopathogenic mechanisms].
AB  - The reactive arthritis is an important clinical entity, which is under intense
      scientific investigation particularly in what concerns to the infective agent and
      the immunological mechanisms involved in its pathogenesis. The infective agents,
      as well as the antigens and the cellular immune response lead to arthritis after
      a sequence of events. Some important aspects, such as the genetic predisposition
      of some individuals, the intracellular life cycle of the bacteria, the mucosal
      membranes as the site of penetration of the infectious agent, as well as the
      lipopolysaccharide as the most important component of the membrane, are
      extensively discussed. The importance of better understanding this disease will
      end up in the amelioration of therapeutic approach.

PMID- 7817094
TI  - [Pulmonary capacity and volume, forced expiratory flow measured by whole body
      plethysmography in acute pancreatitis: experimental study in rats].
AB  - Up to 70% of the patients with acute pancreatitis suffer a sort of pulmonary
      dysfunction. Twenty-nine rats with pancreatitis induced by 2.5% taurocholic and
      solution have been studied by whole body plethysmography in order to evaluate
      pulmonary volumes and expiratory flows. They were divided into three groups: a
      sham operation control group-10 rats,a two pancreatitis group-10 rats and eight
      hours pancreatitis group-9 rats. The results showed a significant decrease of
      expiratory reserve volumes and forced vital capacity (FVC) and also a significant
      increase of expiratory flow in the 2 and 8 hours pancreatitis groups. These
      findings indicate a restrictive pneumopathy.

PMID- 7817095
TI  - [Lymphoma of the biliary tract: report of 2 cases].
AB  - We report two cases one a primary non Hodgkin lymphoma of the hepatic common duct
      and the other a secondary involvement of the biliary tract in a patient with a
      Hodgkin's disease. In the first case a local resection of the biliary lymphoma
      was undertaken being the patient alive six months after the procedure. The second
      case died early after the operative biliary external drainage in a septic shock
      before any specific treatment could be initiated.

PMID- 7817096
TI  - [Acute hemolytic crisis followed by fulminant hepatic failure with fatal outcome,
      as a first clinical manifestation of Wilson's disease].
AB  - We describe in this work a clinical case of a female patient aged 21 years,
      bearer of Wilson's disease, a first clinical manifestation of the disease
      occurred as an acute hemolytic crisis followed by fulminant hepatic failure
      evolving to death after 26 days' internment. The definitive diagnosis was
      obtained only as a quantitative measurement of hepatic copper from the necropsy
      material. The search for Kayser-Fleischer ring was negative and the serum
      ceruloplasmin level was 9 mg/dl (15 to 60). No involvement of the central nervous
      system was noted from the pathologic analysis. The patient presented two Coombs
      negative hemolytic crises during the internment; the first on being admitted to
      hospital and the second after a transjugular hepatic biopsy carried out on the
      16th day after internment. The last hemolytic crisis was accompanied by an
      increase of serum and urinary copper levels. On this occasion the patient evolved
      to a progressive hepatic failure with severe jaundice and hepatic encephalopathy.
      We are presenting the clinical-biochemical evolution of the patient and we shall
      discuss the existent hypotheses to the pathophysiology of this rare form for
      manifestation of the Wilson's disease as well the diagnostic difficulties.

PMID- 7817097
TI  - [Duodenal ulcer clinically simulating pancreatic neoplasm].
AB  - A small fraction of solid mass in the head of the pancreas are inflammatory
      rather neoplastic in origin. The failure to recognize the true nature of a solid
      tumor in the head of pancreas may lead to an incorrect treatment strategy. This
      is a report of a patient with clinical history of pancreatic cancer which
      computed tomography showed a mass in the head of the pancreas with radiologic
      characteristics of malignancy. The patient underwent exploratory laparotomy with
      the finding of a mass in the head of the pancreas. The inflammatory palpable
      characteristic of the mass led to a intraoperative biopsy to confirm the
      preoperative diagnosis. With the benign result of the biopsy, the final diagnosis
      was duodenal ulcer which penetrates in the pancreatic parenchyma.

PMID- 7817098
TI  - [Levels of care in nutrition].
AB  - The dietitian's role includes diverse activities such as planning of the
      nutritional assistance, teaching and researching. The nutritional strategy varies
      according to the levels of the dietetic assistance being related to the nature of
      the disease and to the medical treatment the patient is undergoing. The
      assistance level classification helps the standardization of the procedures.

PMID- 7817099
TI  - [Degree of satisfaction in the users of the Central Institute of the Clinical
      Hospital-PAMB for the care received].
AB  - Through a sample of 1346 ambulatory patients, correspondent to the 3% monthly
      attendance of the ICHC/PAMB in the first semester of 1992, the authors report the
      degree of satisfaction of the population assisted. The survey reveals the
      performance of the multiple professionals as well as the evaluation of the
      ambulatory facilities regarding signs, hygiene and general organization of
      services, etc. The parameters, specially those concerning the health
      professionals, demonstrate that its concept the patients of the ICHC-PAMB is
      considered good.

PMID- 7817100
TI  - [Institutional and departmental teaching hours of 2 curricula at the medical
      school of the Sao Paulo University--comparative analysis].
AB  - The teaching results of the curriculum adopted at the Medical School of the
      University of Sao Paulo in the last three years were compared with those observed
      formerly. There was a diminution of 15.97% of teaching hours at the Institute of
      Biomedical Sciences and an increase of 3.68% of teaching hours at the Medical
      Faculty. The highest increase was observed at the Department of Radiology
      (27.77%) and the lowest at the Department of the Preventive Medicine (40.0%).
      This fact shows that the greater importance was given in the new curriculum to
      the part concerning specialization.

PMID- 7817101
TI  - [The use of microvascular free flaps in the repair of the skin of the upper
      limb].
AB  - Between 1980 and 1992 microsurgical free flaps were used in 35 patients for the
      repair the of skin defects in the upper limb. Twenty six patients were male and
      nine female. The scapular flap was done in 16 cases, the lateral flap in seven,
      the dorsalis pedis in four, the neurovascular first web space in four, the
      latissimus dorsi in two, the radical forearm flap in one and the gracilis in
      other one. The survival rate in this series was 88.57%. Early free flaps were
      performed in 12 patients of whom one developed infection at the recipient site.
      Two-point discrimination was achieved in four thumbs reconstructed with the
      neurovascular first web flap. No complications occurred at the donor areas.

PMID- 7817102
TI  - [Pathologic synovial plica of the knee. Results of surgical treatment in 37
      knees].
AB  - The authors present their results on the surgical treatment of pathologic
      synovial plica in 69 knees of 66 patients. In all patients the synovial plica was
      the primary pathology and there where no associated knee pathologies. 36 knees
      were operated between 1979 and 1986 by an open procedure, and 33 had arthroscopic
      surgery from 1986 to 1991. All patients had previous unsuccessful conservative
      treatment. The operation was a partial sinovectomy, including all the extension
      of the synovial plica. The results were obviously superior in the arthroscopic
      procedure, with 100% of excellent results and quick recovery. All patients in
      this group had a full range of knee movements by the end of the second week after
      surgery. In the open surgery group, only 76% of the results were excellent and
      the full range of movements was obtained only by the fourth or fifth week.

PMID- 7817103
TI  - [Surgical approach in the treatment of supra-condylar fractures of the humerus in
      children].

PMID- 7817104
TI  - [Traumatic spondylolysis].
AB  - The authors present the results of treatment of seven cases of spondylolysis with
      a two years follow up. Six patients were treated with the thoracolumbosacral
      orthosis and one with L5-S1 fusion. At the end of the follow up all patients were
      pain free.

PMID- 7817105
TI  - [Treatment of pseudarthrosis of the long bones using the Ilizarov method in
      children].
AB  - In the period 1987-1993, 13 patients were treated for both infected and non
      infected long bone pseudoarthrosis by Ilizarov method. The records and
      radiographs of nine boys and four girls, with the age ranging from 7 to 16 years,
      with an average of 12.3 years, were reviewed. All but one concerned the tibia. In
      one case the pseudoarthrosis was localized in the humerus. Ten were infected. Ten
      had bone loss, all in the tibia, 2.5 to 8.0 cm in the extension of. All the
      results were considered good and the complications observed were few and not
      related with the treatment.

PMID- 7817106
TI  - [The use of hydroxyapatite in the surgical treatment of benign non aggressive
      bone lesions].
AB  - The authors studied, in the period 1990-1993, 31 patients with benign non
      aggressive bone lesions, surgically treated with intralesional resection followed
      by the introduction of hydroxyapatite. Their follow-up was two years and one
      month. The authors discussed the surgical indications, the operative technique
      employed, and the post-operative results which were considered to be good in 29
      of the patients studied. Occurred complications in three patients: local
      infections in two and sterile fistula in one. It is concluded that the use of
      hydroxyapatite is a good option as substitute of the autologous bone graft.

PMID- 7817107
TI  - [Transfer of the pronator teres tendon to the extensor carp radialis tendon in
      wrist flexion deformity in cerebral palsy].
AB  - The flexion deformity of the wrist in cerebral palsy is quite common, carrying
      disability to the effective use of the hands. From 1980 to 1990, 36 transferences
      of the pronator teres to the extensor carpi radialis were reviewed. The authors
      describe the operative technique by a unique incision, that may be used in
      cerebral palsy, and conclude that it is a good method for correction of
      deformity.

PMID- 7817108
TI  - [Lead poisoning caused by a bullet in the hip. Report of 2 cases].
AB  - Two cases of lead poisoning from retained bullets in the hip region are reported.
      General considerations about lead intoxication are made and the intoxication
      caused by bullets retained in the body are specifically focused.

PMID- 7817109
TI  - [Esophageal injury in the anterior approach of the cervical spine].
AB  - The esophageal injuries as complications of the anterior approach to the cervical
      spine are rare. The authors present a case of esophageal perforation with a screw
      employed in an anterior fixation of the cervical spine.

PMID- 7817110
TI  - [Graft bone associated with hydroxyapatite and reconstructive plate as treatment
      in a case of mandibular osteomyelitis].
AB  - A case report of the mandibular osteomyelitis, after the deciduous tooth
      extraction at the age of five years. The patient was submitted to reconstructive
      inclusion graft bone and hydroxyapatite.

PMID- 7817112
TI  - [Physiopathology and clinical evaluation of spasticity].
AB  - The spasticity is a motor alteration of the muscle tonus caused by the spinal
      reflex hyperactivity, related to the increasing of the muscle reaction to the
      stretching. It is very frequent in the upper motor neuron lesional.

PMID- 7817113
TI  - [Surgical approach to giant cell tumors of the distal radius].
AB  - The authors review 15 patients with giant cell tumor of the distal part of the
      radius in the period from 1980 to 1993. Pain was always present. The treatment of
      stage 2 with marginal resection and methylmethacrylate yielded excellent result.
      In the treatment of stage 3 the authors emphasize the need of wide resection. In
      these patients the best functional results were obtained with the use of
      vascularized proximal epiphyseal fibular graft, preserving some painless mobility
      of the wrist and forearm.

PMID- 7817111
TI  - [Diagnostic and therapeutic update on osteoporosis].

PMID- 7817115
TI  - Exocrine pancreatic neoplasms in the mummichog (Fundulus heteroclitus) from a
      creosote-contaminated site.
AB  - A high prevalence of exocrine pancreatic neoplasms occurred in mummichog,
      Fundulus heteroclitus, from a creosote-contaminated site in the Elizabeth River,
      Virginia. A total of 20 neoplasms were found in a group of about 1,300 fish
      obtained at this site over a 2-yr period. Of 240 fish collected during October
      1991, 3.3% had pancreatic neoplasms. Adjusted total lesion prevalence for large
      adult fish (Size Class III: total length = 75-85 mm; Size Class IV: total length
      > 85 mm) was 6.7%. Pancreatic neoplasms were not observed in 234 fish collected
      at this site during May 1991, nor were they found in 420 fish obtained during
      fall 1991 from 1 uncontaminated and 6 moderately contaminated localities. Lesions
      involved both mesenteric and intrahepatic exocrine pancreas and ranged from well
      differentiated acinar cell adenomas to poorly differentiated acinar cell
      carcinomas. One fish had an atypical acinar cell focus. All specimens with
      pancreatic neoplasms also had hepatocellular lesions. This epizootic of exocrine
      pancreatic neoplasia is the first to be reported in a wild fish population. Based
      on chemical characterization of the site and limited experimental data on
      chemically induced pancreatic carcinogenesis in other small fish species, the
      neoplasms were probably caused by exposure of the mummichog to chemical
      carcinogens in their environment.

PMID- 7817116
TI  - Ultrastructure of normal and neoplastic exocrine pancreas in the mummichog,
      Fundulus heteroclitus.
AB  - The ultrastructure of exocrine pancreatic neoplasms occurring in the mummichog,
      Fundulus heteroclitus, from a creosote-contaminated site in the Elizabeth River,
      Virginia, is described and related to nonneoplastic exocrine pancreas. Normal
      mummichog pancreas was an anastomosing tubular gland, with parenchymal cells
      organized as branched, anastomosing tubules around a central ductular system. The
      pancreatic ductular system consisted sequentially of terminal canalicular lumens
      lined by acinar cells, pancreatic preductules formed by an acinar and a
      centroductular cell, pancreatic ductules lined by 2 centroductular cells, and
      pancreatic ducts lined by cuboidal or columnar epithelial cells resting on a
      basal lamina and stromal sheath. Acinar cell adenomas retained the normal tubular
      organization and relationship between acinar and centroductular cells. Tumor
      cells exhibited nuclear pleomorphism but contained a full complement of normal
      zymogen granules and rough endoplasmic reticulum (RER). Some adenomas exhibited
      necrosis and cellular degeneration. Acinar cell carcinomas ranged from well to
      poorly differentiated. They exhibited loss of cell polarity, moderate to severe
      nuclear pleomorphism, extensive variation in size, shape, and number of zymogen
      granules, variability in RER content, and cellular degeneration. Acinar cell
      neoplasms in the mummichog were similar to those induced chemically in other
      fishes and certain mammals, suggesting that this fish population has been exposed
      to potent chemical carcinogens and that the species may be an effective indicator
      of polluted estuarine environments.

PMID- 7817114
TI  - Pleural lesions in Syrian golden hamsters and Fischer-344 rats following
      intrapleural instillation of man-made ceramic or glass fibers.
AB  - The mesothelium is a target of the toxic and carcinogenic effects of certain
      natural mineral and man-made fibers. Long-term inhalation of a ceramic fiber (RCF
      1) results in a high incidence of pleural mesotheliomas in Syrian golden hamsters
      but not in identically exposed Fischer-344 rats. The present study compared the
      histopathology of the early pleural response in rats and hamsters instilled with
      artificial fibers. Groups of Syrian golden hamsters and Fischer-344 rats were
      instilled with ceramic (RCF-1) or glass (MMVF-10) fibers directly into the
      pleural space. Each species received approximately equal numbers of long, thin
      fibers per g body weight. Fiber-induced lesions were compared 7 and 28 days
      postinstillation. Both hamsters and rats developed qualitatively similar dose
      dependent inflammatory lesions that were not fiber-type specific. Both species
      developed fibrosis in conjunction with inflammation in the visceral pleura, but a
      striking interspecies difference was noted in the pattern of mesothelial cell
      response. Hamsters developed greater surface mesothelial cell proliferation and
      had focal aggregates of mesothelial cells embedded deep within regions of
      visceral pleural fibrosis. It is hypothesized from the present study that the
      marked fiber-induced proliferative mesothelial cell response of the hamster
      visceral pleura may explain the high number of pleural mesotheliomas found in
      long-term fiber studies in this species.

PMID- 7817117
TI  - Sequential observation of spontaneous endometrial adenocarcinoma development in
      Donryu rats.
AB  - Sequential observation of spontaneous endometrial adenocarcinoma development
      revealed a clear, hormone-dependent, histogenetic pathway in Donryu rats. The
      first histological changes of the uterine endometrium appeared in both the lining
      epithelium and uterine gland of the endometrium at 6 mo of age, along with the
      beginning of persistent estrus. These changes included areas of tall columnar
      epithelium and gland formation in the lining epithelium as well as metaplastic
      change in the uterine gland. At 8 mo of age, endometrial hyperplasias were found,
      with subsequent increase in both incidence and degree. At 8-10 mo of age,
      hyperplasias were all within the limit of grade ++. After 12 mo of age, however,
      severe hyperplasias (grade ) began to increase markedly, and adenocarcinomas
      developed at 15 mo of age. The findings thus suggest that uterine endometrial
      adenocarcinomas arise from hyperplastic lesions, which should therefore be
      regarded as preneoplastic, as in the human case. Sequential analysis of plasma
      gonad steroids also ascertained a link between the appearance of these lesions
      and an increased estrogen:progesterone ratio, suggesting that estrogen may play
      an important role in development of both hyperplastic and neoplastic lesions. In
      Fischer-344 rats used for comparative assessment of strain differences, neither
      advanced histological changes nor hormonal changes were evident.

PMID- 7817118
TI  - Tumor-promoting effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin and phenobarbital
      in initiated weanling Sprague-Dawley rats: a quantitative, phenotypic, and ras
      p21 protein study.
AB  - In an initiation-promotion protocol, female weanling Sprague-Dawley rats were
      initiated with 10 mg/kg nitrosodiethylamine and promotion was started after 30
      days. Promotion regimens were as follows: 2,3,7,8-tetrachlorodibenzo-para-dioxin
      (TCDD; 150 ppt in diet) continuously until day 450; phenobarbital (PB; 500 ppm in
      diet) until day 170; PB until day 170, followed by TCDD until day 240; and PB
      until day 170, followed by a basal diet (BD) until day 240 and subsequently TCDD
      from days 240 to 450. TCDD fed to initiated rats had a promoting effect on the
      development of adenosine triphosphatase-negative altered hepatocellular foci
      (AHF). At 450 days, the volume fraction of liver occupied by AHF was increased in
      initiated rats given TCDD continuously and in those given PB followed by TCDD,
      whereas the mean volume of AHF was significantly larger in initiated rats given
      TCDD continuously. PB and TCDD promoted similar phenotypes of AHF as seen in
      hemotoxylin and eosin-stained sections, but the eosinophilic phenotype most
      closely correlated with the development of hepatocellular neoplasms. The
      protooncogene product ras p21 protein was present in the majority of PB- and TCDD
      promoted AHF, hepatocellular adenomas, and hepatocellular carcinomas.
      Eosinophilic AHF and ras p21 protein expression most closely correlated with
      neoplastic development, suggesting that these cell populations, when promoted,
      may be at greater risks for developing into neoplasms.

PMID- 7817119
TI  - Effect of phenobarbital and mirex pretreatments on CCl4 autoprotection.
AB  - Male Sprague-Dawley rats maintained on either normal diet (N) or on a diet
      containing phenobarbital (PB; 225 ppm) or mirex (M; 10 ppm) for 15 days received
      either corn oil or 1 single administration of a protective dose of CCl4 (0.3
      ml/kg, po) on day 16. At 24, 48, 72, 96, or 144 hr after the protective dose, a
      high dose of CCl4 (5 ml/kg, po) was administered to rats of all the groups, and
      they were observed for 14-day lethality. In a second experiment, in rats
      maintained on N, PB, or M diet, liver microsomal cytochromes P-450, aminopyrine
      demethylase, and aniline hydroxylase were measured at various time points after
      the administration of the protective dose of CCl4. Serum aspartate transaminase,
      alanine transaminase, and sorbitol dehydrogenase elevations and histopathological
      changes observed under a light microscope were used as toxic end points to assess
      hepatotoxicity. Autoprotection was 100% when the high dose was given at 24 hr
      after the protective dose in N rats, whereas it was only 55% in PB- or M
      pretreated rats. For later time points of 48, 72, and 96 hr, autoprotection was
      only around 50% in N rats, whereas it was almost 100% in PB- and M-pretreated
      rats. When the high dose was administered at 144 hr after the protective dose,
      autoprotection further declined to 25% in N rats and to 75% in M-treated rats,
      but it remained at 100% in PB-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7817120
TI  - The effects of overfeeding and dietary restriction on Sprague-Dawley rat survival
      and early pathology biomarkers of aging.
AB  - A significant correlation exists between average daily food consumption and 2-yr
      survival in control ad libitum (AL)-fed Sprague-Dawley (SD) rats. SD rats were
      fed Purina Rodent Chow 5002 or a modified chow, 5002-9, with lower protein, fat,
      metabolizable energy and increased fiber AL or by dietary restriction (DR) to 65%
      of the AL amount by measurement or time (6.5 hr). At 52 wk, food consumption and
      key pathology biomarkers correlated with 106-wk survival. The modified chow, 5002
      9 fed AL, did not significantly improve survival. SD rats fed either diet AL
      consumed the greatest amount of feed and kcal/rat but consumed the same amount of
      feed per gram body weight as DR-fed rats. At 52 wk, AL rats fed either diet had
      the same brain weights as DR rats, but the AL-fed rats had greater body weight
      and body fat content and increased heart, lung, kidney, liver, adrenal, thyroid,
      and pituitary weights as well as an increased incidence and severity of
      degenerative and/or proliferative lesions in these organs. This study
      demonstrates that overfeeding best correlates with low 2-yr survival in SD rats
      and that simple DR by caloric restriction modifies key pathology biomarkers in
      the pituitary, mammary gland, kidney, and heart of SD rats at 52 wk that are
      predictive of 106-wk survival.

PMID- 7817121
TI  - Alterations in glomerular anionic sites in canine anti-glomerular basement
      membrane nephritis with onset of severe proteinuria.
AB  - Rabbit anti-glomerular basement membrane serum (AGBM) or normal rabbit serum
      (NRS) were given intravenously (2 ml/kg body weight) to 8 male beagle dogs. Light
      and transmission electron microscopy and immunofluorescence were performed on the
      kidneys on day 7 postinjection. Alterations of anionic sites (ASs) of glomerular
      basement membrane (GBM) in peripheral, proximal, and paramesangial portions were
      studied quantitatively by electron microscopy using polyethyleneimine (PEI;
      molecular weight = 1,800) as a cationic probe. Severe or mild proteinuria
      developed on day 1 and continued until day 6 postinjection. On day 7 after AGBM
      injection, the number of PEI granules per 1,000 nm length of the lamina rara
      externa of GBM in all portions was significantly less than that in NRS-treated
      dogs (10.48 +/- 1.78 versus 14.19 +/- 2.35 granules per 1,000 nm of GBM in
      peripheral portion, 10.81 +/- 1.91 versus 14.97 +/- 1.35 granules per 1,000 nm of
      GBM in proximal portion, 8.44 +/- 1.76 vs 13.43 +/- 2.10 granules per 1,000 nm of
      GBM in paramesangial portion; p < 0.001). These results indicate that a reduction
      glomerular AS occurs in AGBM-treated dogs in association with severe or mild
      proteinuria and alterations in glomerular ASs might play an important role in the
      pathogenesis of proteinuria in the canine anti-GBM nephritis in addition to
      morphological changes.

PMID- 7817122
TI  - The rat as a model to evaluate the gastric irritation potential of alkaline
      products.
AB  - Animal models historically used to assess the acute gastric irritation potential
      of accidental ingestion of consumer products include the dog, pig, rabbit, and
      cat. In looking at alternative methods that are of shorter duration and more cost
      effective, the rat is being evaluated as a potential model. Acute gastric
      irritation is known to increase as the reserve alkalinity of the formulation
      increases. In initial experiments to assess the rat as a potential model, animals
      were dosed via oral gavage with 1 of 4 formulations ranging in reserve alkalinity
      from 4.0 to 10.8. Necropsies were performed at 15 and 60 min after dosing.
      Macroscopic and microscopic evaluations of the stomach revealed morphological
      differences in the various treatment groups that distinguish granular
      formulations having either a low (R.A. = 4.0), moderate (R.A. = 7.1), or higher
      (R.A. = 10.8) reserve alkalinity. Additionally, it was observed that the acute
      gastric changes in rats dosed with a liquid formulation having a low (R.A. = 4.2)
      reserve alkalinity were similar to those in rats dosed with a granular
      formulation having a moderate reserve alkalinity (R.A. = 7.1). This suggests that
      other factors such as types of ingredients, pH, and physical form influence the
      extent of acute gastric irritation and demonstrates that an evaluation of only
      reserve alkalinity is not sufficient to ensure the safety of these products. This
      preliminary work supports the rat as a potential model to assess the acute
      gastric irritation potential of alkaline formulations or substances.

PMID- 7817123
TI  - Toxicologic pathology: modern challenges and the need for a new educational
      strategy.

PMID- 7817124
TI  - Pathologic effects of butylated triphenyl phosphate-based hydraulic fluid and
      tricresyl phosphate on the adrenal gland, ovary, and testis in the Fischer-344
      rat.
AB  - Triaryl phosphates including tricresyl phosphate (TCP) and butylated triphenyl
      phosphates (BTPs) are used in the commercial manufacture of plastics, lubricants,
      and hydraulic fluids. Recent reports implicate these compounds as endocrine and
      reproductive toxicants in rodents. The objectives of this study were to develop
      and characterize a rat model to investigate the mechanism(s) of toxicity of
      triaryl phosphate-based hydraulic fluids and to elucidate potential mechanistic
      pathways of toxicity through studies of structural/functional relationships.
      Groups of male and female rats received daily oral doses of either sesame oil
      alone or 1.7 g/kg of BTP or 0.4 g/kg TCP in sesame oil vehicle or 2.8 g/kg neat
      BTP for 20, 40, and 60 days. Light microscopic, morphometric, ultrastructural,
      and histochemical studies revealed hypertrophy and cholesteryl lipidosis of
      adrenocortical (both sexes) and ovarian interstitial cells that were progressive
      with duration of exposure. Minimal degeneration was observed in the adrenal
      cortex and ovary. TCP caused the most severe lesions in both the adrenal gland
      and ovary, but the morphologic and histochemical changes produced were similar
      for both compounds, suggesting a common mechanism of toxicity. Decreased
      testicular weight and degeneration of seminiferous tubules were detected only in
      TCP-treated rats. The Fischer-344 rat model using TCP and BTP administered by
      gavage is a valuable system to study mechanisms of endocrine and reproductive
      toxicity induced by triaryl phosphate-based hydraulic fluids.

PMID- 7817125
TI  - Nasal diagrams: a tool for recording the distribution of nasal lesions in rats
      and mice.
AB  - Knowledge of patterns of lesion distribution can provide insight into the
      relative roles played by regional tissue dose and local tissue susceptibility in
      toxic responses to xenobiotics in the nose and assist assessment of potential
      human risk. A consistent approach is needed for recording lesion distribution
      patterns in the complex nasal airways of rats and mice. The present work provides
      a series of diagrams of the nasal passages of the Fischer-344 rat and B6C3F1
      mouse, designed for mapping nasal lesions. The diagrams present each of the major
      cross-sectional airway profiles, provide adequate space for nasal mucosal lesion
      recording, and are suitable for duplication in a commercial photocopier. Sagittal
      diagrams are also provided to permit transfer of lesion location data observed in
      transverse sections onto the long axis of the nose. The distribution of lesions
      induced by a selected range of xenobiotics is presented. Approaches to
      application of the diagrams and interpretation of results obtained are discussed
      in relation to factors responsible for lesion distribution in the nose and their
      relevance to interspecies extrapolation. A modified approach to anatomical
      classification of the ethmoturbinates of the rodent is also presented.

PMID- 7817126
TI  - Induction of the renal pelvic and ureteral carcinomas by N-butyl-N-(4
      hydroxybutyl)nitrosamine in SD/cShi rats with spontaneous hydronephrosis.
AB  - We attempted to establish an animal model for renal pelvic and ureteral
      carcinomas. In Experiment 1, Sprague-Dawley (SD)/cShi and SD/gShi strains of male
      and female rats and Fischer-344 (F-344)/DuCrj and LEW/Crj strains of male rats, 6
      wk old, were given 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) for 12 wk
      and then treated without chemical for 10 wk. Only the SD/cShi strain, which has
      spontaneous hydronephrosis and hydroureter, showed high incidences of carcinomas
      in the renal pelvises and ureters, whereas the other strains did not. In
      Experiment 2, SD/cShi and Crj:CD strains of male and female rats, 6 wk old, were
      exposed to 0.05% BBN for 20 wk. Both sexes of SD/cShi rats had high incidences of
      bilateral carcinomas in renal pelvises and/or ureters associated with urinary
      bladder carcinomas, whereas both sexes of Crj:CD rats had urinary bladder tumors
      only. These results indicate that the SD/cShi strain may be a suitable animal for
      the induction of renal pelvic and ureteral carcinomas that appear to depend on
      urine stagnation secondary to hydronephrosis and hydroureter.

PMID- 7817128
TI  - Effects of a synthetic polyprenoic acid (E-5166) on the gap junction of rat
      hepatocytes treated with liver tumor promoters, phenobarbital, and p,p'
      dichlorodiphenyltrichloroethane.
AB  - Effects of in vivo exposure to the synthetic polyprenoic acid, 3,7,11,15
      tetramethyl-2,4,6,10,14-hexadecapentaenoic acid (E-5166) using 6 groups of rats
      treated simultaneously or individually with phenobarbital (PB) or with p,p'
      dichlorodiphenyltrichloroethane (DDT) on the gap junctions of hepatocytes were
      examined by freeze-fracture analysis. Experimental groups were as follows: Group
      1, basal diet alone; Group 2, E-5166 treatment; Group 3, 0.05% PB diet; Group 4,
      PB diet and E-5166 treatment; Group 5, 0.05% DDT diet; and Group 6, DDT diet and
      E-5166 treatment. E-5166 was given by gavage (40 mg/kg body weight, 3 times/wk).
      Experimental diets and E-5166 were started at 6 wk of age. All animals were
      sacrificed at 2 wk after the start of the experiments. The density of gap
      junctions in PB- or DDT-treated rats was higher and that in E-5166-treated rats
      was lower than that in controls. The density of gap junctions in rats given PB
      and E-5166-/or DDT and E-5166-treated rats was slightly increased when compared
      to controls. The average area of gap junctions in DDT- or PB and E-5166-treated
      rats was significantly smaller than in controls (p < 0.005), although no
      statistical differences were found among PB-, E-5166-, and DDT and E-5166-treated
      rats and controls. Unit area of gap junctions to membrane area in rats given E
      5166, DDT, or PB and E-5166 was lower than in controls. However, the unit area of
      gap junctions in DDT and E-5166-treated rats did not differ from in
      controls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7817129
TI  - Hepatotoxicity in guinea pigs following acute inhalation exposure to 1,1-dichloro
      2,2,2-trifluoroethane.
AB  - Groups of 10 male Hartley guinea pigs were exposed to 3.0, 2.0, 1.0, or 0.1%
      (v/v) 1,1-Dichloro-2,2,2-trifluoroethane (HCFC-123) or 1.0% (v/v) halothane by
      inhalation for 4 hr. A sixth group of 10 guinea pigs received only air. All
      animals were sacrificed 48 hr postexposure. Gross and histopathologic examination
      of the liver, heart, and kidney and routine hematology and clinical chemistry
      analyses [including isocitrate dehydrogenase (ICDH)] were done on all guinea
      pigs. Lesions related to HCFC-123 and halothane exposure were limited to the
      liver and included centrolobular vacuolar (fatty) change, multifocal random
      degeneration and necrosis, and centrolobular degeneration and necrosis. These
      lesions were observed in 90-100% of the exposed animals and were absent in the
      air-only controls. There was significant individual animal variation in
      susceptibility to both HCFC-123 and halothane, resulting in a spectrum of
      histologic lesions and clinical chemistry values within each exposure group.
      Alanine aminotransferase, aspartate aminotransferase, and ICDH were the most
      significant predictors of hepatocellular damage. Similarities in the response
      between halothane and HCFC-123 in this guinea pig model suggests that humans
      susceptible to halothane-induced hepatitis may be susceptible to HCFC-123 by a
      common mechanism of toxicity.

PMID- 7817127
TI  - Interleukin-1 alpha reduces the severity of the vascular leak syndrome produced
      by interleukin-2 and interleukin-2 plus interferon-alpha.
AB  - Histological and ultrastructural changes were investigated in lung, liver, and
      heart of mice given interleukin-2 (IL-2), either alone or in combination with
      other cytokines. IL-2 induced a vascular leak syndrome (VLS) of a moderate degree
      with infiltration of lymphoid cells, moderate endothelial damage, mild hepatic
      parenchymal damage, and minimal myocardial alterations. Interferon-alpha (IFN
      alpha) produced infiltration mainly of monocytes/macrophages in liver and heart;
      endothelial cell damage was absent in lung and heart and minimal in liver.
      Interleukin-1 alpha (IL-1 alpha) caused an increased number of neutrophils in
      liver and lung; VLS and parenchymal cell and endothelial damage were not found.
      The VLS and the cellular damage caused by the combination of IL-2 and IFN were
      much more severe than those produced by IL-2 alone. In animals treated with IL-2,
      IFN-alpha, and IL-1 alpha, VLS was minimal and parenchymal and endothelial cell
      damage were less severe than after IL-2 alone or IL-2 plus IFN-alpha. Taken
      together, these observations show that IL-1 alpha reduces ultrastructural changes
      produced by IL-2 and IFN-alpha. This reduction may be clinically useful in the
      treatment of neoplasms.

PMID- 7817130
TI  - Enzymic pattern of preneoplastic and neoplastic lesions induced in the kidney of
      CBA mice by 1,2-dimethylhydrazine.
AB  - Mouse renal cell tumors (RCTs) were induced in male CBA mice by 5 subcutaneous
      injections of 8 mg 1,2-dimethylhydrazine (DMH)/kg body weight once a week. After
      a lag period of 2 yr kidneys were removed, and serial cryostat sections of the
      kidneys were histochemically analyzed for the following parameters: glycogen
      content, basophilia, and the activities of glycogen synthase (SYN), glycogen
      phosphorylase (PHO), glucose-6-phosphatase (G6Pase), glucose-6-phosphate
      dehydrogenase (G6PDH), hexokinase (HK), pyruvate kinase (PK), lactate
      dehydrogenase (LDH), malic enzyme (ME), succinate dehydrogenase (SDH), alkaline
      phosphatase (ALPase) and gamma-glutamyltranspeptidase (GGT). RCTs displayed the
      same histochemical profile irrespective of their size and growth pattern. In
      comparison with the normal kidney epithelium, the neoplastic cells exhibited
      elevated activities of enzymes for glycolysis (HK, PK, LDH) and the pentose
      phosphate pathway (G6PDH), while negative G6Pase and low SDH activity were
      observed in these cells. The majority of RCTs showed high PHO activity and weak
      staining for SYN. Activities of ALPase and GGT were negative in most of the RCTs.
      Markedly enlarged cells with atypical nuclei were detected in some advanced RCTs.
      Higher activities of glycolytic and mitochondrial enzymes and G6PDH were found in
      these enlarged cells than in other tumor cells. Tubular preneoplastic lesions
      were similar to neoplastic lesions in morphological and histochemical
      characteristics. The present study revealed that a markedly elevated capacity for
      glycolysis and the pentose phosphate pathway occurred in RCTs in mice. A similar
      histochemical pattern in the few preneoplastic tubular lesions observed suggests
      that these metabolic aberrations emerge early during carcinogenesis, but
      additional studies on early stages of renal carcinogenesis are needed to
      substantiate this assumption.

PMID- 7817131
TI  - Spontaneous hemangioendothelial cell hyperplasia of the heart in B6C3F1 female
      mice.
AB  - Spontaneous hemangioendothelial cell hyperplasia of the heart was found in 12 of
      3,910 female B6C3F1(C57BL/6CrSlc x C3H/HeSlc) mice that were used in chronic
      toxicology and carcinogenicity studies at the An-Pyo Center (Shizuoka, Japan).
      Histologically, the lesions appeared diffusely in the heart as widened vascular
      spaces lined by a single layer of endothelial-like cells with enlarged nuclei
      between the muscle fibers. These proliferating cells were identified as
      hemangioendothelial cells by immunohistochemical techniques, lectin-binding
      patterns, and electron microscopic examination. Morphological differences were
      found between this spontaneous hemangioendothelial hyperplasia and that which has
      been reported as a preneoplastic lesions of hemangiosarcoma. Spontaneous
      hemangioendothelial cell hyperplasia of the heart occurs rarely; however, it was
      interesting that spontaneous hemangioendothelial cell hyperplasia was only seen
      in females with adenocarcinomas of the mammary gland.

PMID- 7817134
TI  - Our new system makes nurses better teachers.

PMID- 7817135
TI  - Combating hemorrhagic shock.

PMID- 7817132
TI  - Dissimilar frequency of hepatoblastomas and hepatic cystadenomas and
      adenocarcinomas arising in hepatocellular neoplasms of D2B6F1 mice initiated with
      N-nitrosodiethylamine and subsequently given Aroclor-1254,
      dichlorodiphenyltrichloroethane, or phenobarbital.
AB  - Aroclor-1254 (Ar-1254) and dichlorodiphenyltrichloroethane (DDT) were compared to
      phenobarbital (PB) for their ability to promote hepatocellular proliferative
      lesions to hepatocellular adenomas and carcinomas and to hepatoblastomas in
      D2B6F1 male mice initiated with N-nitrosodiethylamine (NDEA). Hepatocellular
      neoplasms developed in all mice given NDEA and were more numerous in mice fed
      promoters. Multiplicities decreased in the order Ar-1254 > PB > DDT, indicating
      that Ar-1254 was more potent than either PB or DDT at the dosage levels used. PB
      was the most effective of the 3 agents in stimulating the evolution of
      hepatocellular neoplasms to hepatoblastoma. The incidence of hepatoblastomas in
      the NDEA.PB group was 72% but was only 27% in NDEA-initiated, DDT-promoted mice
      and 33% in low-dose and only 9% in high-dose Ar-1254-promoted mice. In contrast,
      lesions resembling benign and malignant cholangiocellular neoplasms were
      frequently found within hepatocellular tumors in Ar-1254-promoted mice but not in
      mice fed PB or DDT, either alone or after NDEA. Some cystic glandular structures
      in Ar-1254-promoted mice contained mucous cells, argentaffin cells, and Paneth
      cells and thus constituted intestinal metaplasia. Hepatoblastoma and intestinal
      metaplasia/cholangiocellular tumor morphology appear to constitute different
      patterns of genetic programming induced by certain promoters in expanding clones
      of initiated hepatocytes, on favorable genetic backgrounds such as that of D2B6F1
      male mice.

PMID- 7817133
TI  - Spontaneous adrenal and hepatic myelolipomas in the common marmoset.
AB  - Myelolipomas occurring simultaneously in the adrenal and liver were found in a
      2.7-yr-old, bred female common marmoset (Callithrix jacchus). The animal bore
      single adrenal and multiple hepatic myelolipomas. The adrenal myelolipoma
      consisted of mature adipose cells and focal collections of normal hematopoietic
      elements and was unencapsulated. In the liver, the myelolipomas, which were
      partially encapsulated, included a large amount of hematopoietic tissue and
      adipose cells that resembled normal bone marrow cells in various ways.
      Additionally, one of the multiple nodules contained several bony spicules with
      osteoblasts. Furthermore, there were invasive figures of hematopoietic cells,
      such as myeloblasts, erythroblasts, and megakaryocytes, in the hepatic sinusoids
      around the lesions. Thus, this case has some unusual morphological
      characteristics and is the first report, to our knowledge, on multiorganic
      myelolipomas in common marmosets.

PMID- 7817136
TI  - The RN pin collection goes silver.

PMID- 7817137
TI  - IV infiltration no clear signs, no clear treatment?

PMID- 7817138
TI  - "Healthy" or "fat"?

PMID- 7817139
TI  - Feeding formulas.

PMID- 7817140
TI  - Nursing's haven for HIV+ patients.

PMID- 7817141
TI  - What is the Supreme Court doing to nursing?

PMID- 7817142
TI  - Should old acquaintance ...

PMID- 7817143
TI  - Try this drug when AIDS-related diarrhea won't quit.

PMID- 7817144
TI  - Helping patients find the best method of controlling pain.

PMID- 7817145
TI  - Rx: laughter, 15 min/day.

PMID- 7817146
TI  - Another method for managing cardiac tamponade.

PMID- 7817147
TI  - Using nutrition as a weapon against breast cancer.

PMID- 7817148
TI  - Effect of hypocalcemic state on enamel formation in rat maxillary incisors.
AB  - Several authors have proposed that hypocalcemia can interfere with amelogenesis,
      resulting in enamel aberrations. Therefore, the purpose of this investigation was
      to study the effects of a diet-induced hypocalcemic state in young rats on enamel
      formation of the maxillary incisors. The experimental rats were fed a special
      diet, free from vitamin D and very low in calcium. The control rats were fed a
      normal diet. The experimental period was 3 wk. After termination, the blood
      analysis showed that the experimental rats had developed hypocalcemia with very
      low values of both total and ionized blood calcium. The experimental rats were
      smaller than their controls after 3 wk, with smaller skulls and teeth. At the
      light microscope level, the enamel and the ameloblasts did not seem to be
      affected, except in one rat, the smallest, which showed enamel hypoplasias in
      both maxillary incisors and a delayed increase of the mineral content during the
      maturation stage process. It is concluded that the hypocalcemic state induced did
      not greatly affect enamel formation. However, occasional enamel aberrations may
      occur.

PMID- 7817149
TI  - Clinical and histologic appearance in enamel of primary teeth in relation to
      neonatal blood ionized calcium values.
AB  - The purpose of this investigation was to study the relationship between low
      values of blood ionized calcium measured in the first days of life postpartum and
      the clinical and histologic appearance of enamel of primary teeth. Twenty-five
      healthy children selected on the basis of optimality with known blood values of
      ionized calcium from the first days of life participated in a dental examination
      at the age of 5 yr. Twenty-four of the children contributed one exfoliated tooth
      each, which was histologically examined. The infants had lower mean values of
      ionized blood calcium on days 1 and 3 than day 5 postpartum. Thirteen of the 25
      children had enamel aberrations, mainly on one tooth each. The histologic
      examination showed normal overall enamel morphology. The neonatal line was
      present in all teeth, and these lines were mostly thin. The registered findings
      about the enamel morphology could not, in any case, be correlated with the
      measured values of neonatal blood ionized calcium.

PMID- 7817150
TI  - Disturbances of cementum formation induced by single injection of 1
      hydroxyethylidene-1,1-bisphosphonate (HEBP) in rats: light and scanning electron
      microscopic studies.
AB  - With the rat molar as a model, evidence is presented that dentin mineralization
      influences formation of acellular cementum. Formation of acellular cementum did
      not occur on the surface of experimentally induced unmineralized dentin. Instead,
      an atypical hyperplastic cementum was formed. The disturbance in acellular
      cementum formation was permanent.

PMID- 7817151
TI  - Oral hygiene in relation to caries development and immigrant status in infants
      and toddlers.
AB  - The purpose of this study was to describe oral hygiene factors in infants and
      toddlers living in Sweden with special reference to caries prevalence at 2 and 3
      yr of age and to immigrant status. The study was designed as a prospective,
      longitudinal study starting with 671 children aged 1 yr. At 3 yr, all the
      children were invited to a further examination. A total of 298 children, randomly
      selected from the original group, were also examined at 2 yr. The accompanying
      parent was interviewed about the child's oral health habits. Children who were
      free of caries at 3 yr had had their teeth brushed more frequently at 1 and 2 yr
      of age, had used fluoride (F)-toothpaste more often at 2 yr of age, and had a
      lower prevalence of visible plaque at 1 and 2 yr of age than children with
      caries. Immigrant children had had their teeth brushed less frequently, had used
      less F-toothpaste, and had a higher prevalence of visible plaque at 1 yr of age
      than nonimmigrant children. Early establishment of good oral hygiene habits and
      regular use of F-toothpaste seem to be important for achieving good oral health
      in pre-schoolchildren.

PMID- 7817152
TI  - Conscious sedation by rectal administration of midazolam or midazolam plus
      ketamine as alternatives to general anesthesia for dental treatment of
      uncooperative children.
AB  - The trial included 24 children (aged 2-7 yr) referred for dental treatment under
      general anesthesia, since conventional behavioral management methods had failed
      to achieve treatment acceptance. As an alternative, they received, on two
      separate occasions with "identical" dental treatment, conscious sedation by
      rectal administration of either midazolam (0.3 mg/kg body weight (bwt)) or
      midazolam (0.3 mg/kg bwt) plus ketamine (1.0 mg/kg bwt). This allowed a double
      blind, crossover design. The aims were to assess conscious sedation, combined
      with local anesthesia, as an alternative to general anesthesia, and further to
      evaluate the effects obtained by addition of a low dose of ketamine to rectally
      administered midazolam. The feasibility of dental treatment was rated as
      excellent or good for 16 of the 24 children when premedicated with midazolam, and
      for 18 of the 24 children when ketamine was added to midazolam. At least some
      treatment could be given to all children. Verbal contact was maintained with all
      children throughout both treatment sessions. The children were significantly less
      anxious when they arrived for the second session. Amnesia and drowsiness were
      significantly increased when ketamine was added to midazolam. The combination
      also tended to be more efficient in relief of anxiety and prevention of pain, but
      there were large variations in the children's responses to the drugs. Midazolam
      significantly reduced the blood oxygen level, but not with ketamine added. For
      most children, both regimens proved to be appropriate as alternatives to general
      anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7817153
TI  - Does the presence of xylitol in a sorbitol-containing chewing gum affect the
      adaptation to sorbitol by dental plaque?
AB  - It is known that xylitol inhibits sorbitol metabolism in some bacteria in vitro.
      The effect of xylitol/sorbitol-containing chewing gum on sorbitol adaptation of
      dental plaque was therefore examined. Ten subjects used this chewing gum for 12
      wk, and plaque was collected before (control plaque) and after (test plaque) the
      exposure to sorbitol/xylitol. The metabolism of sorbitol by the plaque was
      examined with 14C-labeled sorbitol, and the radioactive metabolites were detected
      by high-performance liquid chromatography (HPLC). A considerable individual
      variation in acid formation was found. The mean values of total acids in the test
      plaque increased, as compared with the control plaque. An adaptation of dental
      plaque to sorbitol thus occurred in spite of the presence of xylitol in the
      chewing gum. The concentration of acetic acid predominated over other acids in
      both the control and test plaques. The proportions of acids expressed in
      percentage of total acids differed only slightly. Thus, long-term use of
      xylitol/sorbitol-containing chewing gum did not eliminate the adaptation of
      dental plaque to sorbitol.

PMID- 7817154
TI  - Microradiography of the feline marginal periodontium with a microfocal high
      resolution x-ray system.
AB  - The present paper is a cross-sectional microradiographic study. Postmortem
      hemimandibles were radiographed with a microfocal high-resolution method.
      Microradiographic appearances of the feline periodontium are described and
      discussed. Mean relative alveolar bone support in clinically and histologically
      normal cats was 46.9%. Site-specific alveolar bone support (ABS) was calculated
      twice (blind). The 95% confidence limits of the method error for one observation
      were estimated. Differences between two site-specific measurements did not exceed
      +/- 2.72%. Microfocal radiography yielded valuable additional information about
      the feline periodontium and made it possible clearly to identify important dental
      and periodontal structures such as the CEJ (cementoenamel junction) and the
      bottom of infrabony defects.

PMID- 7817155
TI  - Clinical study of patients with burning mouth.
AB  - Analysis and treatment of dental and medical factors that can cause burning mouth
      were performed in 25 consecutive patients according to a treatment protocol. The
      effect of the dental and medical treatment on the burning mouth was evaluated.
      The sick leave profile was presented. Apart from burning mouth symptoms, the
      patients reported several oral and general symptoms, such as gustatory changes,
      xerostomia, back and joint muscle pain, headache, and dizziness. The most common
      dental diagnoses were temporomandibular joint, masticatory, and tongue muscle
      dysfunction and lesions in the oral mucosa. The most common medical diagnoses
      were low serum iron and hypersensitive reaction to mercury. None of the patients
      tested exceeded the limit of 100 nmol Hg/l urine. Replacement of amalgam fillings
      was the most common dental therapy, followed by treatment of dysfunction in the
      masticatory system. Iron replacement was the most frequent medical treatment. The
      patients had over 50% more days per year sick leave than an age- and sex-matched
      normal population. A follow-up found that the burning mouth had disappeared in
      32% of the patients. This study confirms the opinion that burning mouth is
      multicausal. Hypersensitive reaction to mercury was more frequent than expected,
      but replacement of amalgam fillings relieved burning mouth in only two of five
      such patients, and one of these two patients had hypersensitive reactions to both
      mercury and gold. One reason that so many patients continued to have burning
      mouth might have been neglect of dental, medical, or both diagnoses. Another
      reason might be that assessment of the psychologic status of the patients and
      psychologic treatment when indicated were not done.

PMID- 7817157
TI  - Effect of maxillary edentulousness on mandibular residual ridges.
AB  - Bone mineral density (BMD) was measured in five different regions of the mandible
      of 77 postmenopausal women. These women were also classified according to the
      remaining, clinically determined alveolar height in the edentulous distal regions
      of the mandible. The duration of edentulousness in the maxilla and in the
      mandible was determined anamnestically. All subjects were edentulous in the
      maxilla, and 42 were also edentulous in the mandible. The other 35 women had
      teeth only in region d35-d45. This study shows that after extraction of the last
      teeth in the mandible, the BMD of the cortical bone is not lowered, but that the
      BMD of the trabecular portion is lowered more by mechanical stress caused by the
      remaining natural teeth than by maxillary dentures. This feature becomes apparent
      when duration of edentulousness in the maxilla is compared with the BMD values of
      different regions in the mandible.

PMID- 7817156
TI  - Organic solvents and oils as vehicles for triclosan in mouthrinses: a clinical
      study.
AB  - Previous experiments have shown that the nature of the detergents used in aqueous
      triclosan-containing mouthrinses affects the plaque-inhibiting effect of these
      mouthrinses, probably because of the properties of the micelles formed. It has
      also been shown that triclosan has a marked plaque-inhibiting effect when
      dissolved in pure propylene glycol. The aim of the present study was to compare
      the clinical effect of triclosan dissolved in oils and in the pure solvents
      glycerol (GLY) and polyethylene glycol (PEG). A test panel of 12 volunteers
      rinsed with the allocated mouthrinses for 4 days in a double-blind, crossover
      study. Three different oils were tested: olive oil, soy oil, and sunflower seed
      oil, as well as PEG and GLY. Triclosan was used in a 0.3% concentration to
      facilitate comparison with previous studies. However, only 0.15% triclosan was
      added to the GLY-containing rinse (maximum soluble concentration). In addition,
      soy oil without triclosan was tried. The mean plaque score for water was 1.42 +/-
      0.19; for olive oil, 1.08 +/- 0.34; for soy oil with triclosan, 0.95 +/- 0.35;
      for pure soy oil, 0.94 +/- 0.09; for sunflower seed oil, 1.19 +/- 0.19; for PEG,
      1.04 +/- 0.22; and for GLY, 1.12 +/- 0.28. The results indicate that triclosan
      dissolved in oils loses its clinical effect. However, oils in themselves exhibit
      significant plaque inhibition. In vitro tests showed no antibacterial activity of
      triclosan dissolved in oils. Toothpastes and mouthrinses contain flavoring oils
      and occasionally also GLY and PEG. Such substances may well interfere with the
      clinical effect of triclosan in these products.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7817158
TI  - Urodynamic examination of the lower urinary tract in children with normal and
      congenital neurogenic bladder.

PMID- 7817159
TI  - Metabolic factors and outcome of organ transplantation.
AB  - Chronic vascular rejection (CVR)--transplant atherosclerosis--is a major problem
      in organ transplantation and a leading cause of late graft failure. The purpose
      of the present investigation was to examine the impact of metabolic factors on
      the outcome of experimental and clinical transplantation. In an experimental
      model of CVR in rat cardiac allografts it was shown that the development of
      proliferative vascular lesions, characteristic of CVR, was accelerated 2-4 times
      by a cholesterol enriched diet. Renal transplant patients with manifest CVR had
      hyperlipoproteinaemia and atherogenic lipid patterns, the degree of which
      correlated with the histopathological severity of CVR and was only partially
      explained by renal dysfunction. The influence of pre-existing lipoprotein
      abnormalities on graft function was investigated prospectively in renal
      transplant recipients. It was found that patients with pretransplant
      hypercholesterolaemia had an increased number of acute rejection episodes, worse
      graft function and a higher degree of vascular intimal hyperplasia at six months
      posttransplantation and more graft losses during follow-up. Oxidatively modified
      LDL may be the link between hypercholesterolaemia and graft failure. Plasminogen
      activator inhibitor type-1 (PAI-1), a major inhibitor of fibrinolysis and another
      risk factor for atherothrombosis, which is associated with features of the
      metabolic risk factor syndrome (Syndrome X) was also followed prospectively.
      Patients presenting with all features of this syndrome six months after
      transplantation were at increased risk of losing their graft during a three-year
      follow-up. Pretransplant hypercholesterolaemia was associated with a more than a
      two-fold increase in the risk of graft failure during the first two
      posttransplant years, and elevated PAI-1 levels before transplantation with a
      five-fold increase during the first three years. A chronic graft damage (CGD)
      score was constructed for glomerular, vascular and tubulointerstitial changes
      characteristic of CVR. The CGD score at six months was higher in patients with
      hypercholesterolaemia or elevated PAI-1 activity before transplantation. An
      elevated CGD score at six months predicted an eight-fold increase in the risk of
      renal allograft failure within three years following transplantation. It can be
      anticipated that intervention directed against lipid abnormalities or other
      metabolic risk factors may improve the long-term success rate in organ
      transplantation.

PMID- 7817160
TI  - Fine needle aspiration biopsy for diagnosis and follow-up of prostate cancer.
      Consensus Conference on Diagnosis and Prognostic Parameters in Localized Prostate
      Cancer. Stockholm, Sweden, May 12-13, 1993.
AB  - Fine needle aspiration biopsy (FNAB) and ultrasound-guided core biopsy using
      biopty gun both have a high, and approximately equal, accuracy in diagnosing and
      grading prostate cancer. The TRUS-guided technique provides a better estimation
      of the tumor extent and to some degree even of capsular involvement. It is
      therefore a recommendable part of the preoperative evaluation when radical
      prostatectomy is contemplated. On the other hand, the aspiration technique
      usually provides more epithelial cells. It entails a significantly lower risk of
      septic complications and of seeding tumor cells. It has also a lower cost than
      the core biopsies. The aspiration biopsy can easily be performed repeatedly in
      the follow-up procedure, which is of particular importance in cases managed with
      watchful waiting. We recommend the aspiration biopsy for routine use in the
      diagnostic work-up and follow-up. It is essential that not only the cytologic
      evaluation but as well the sampling from the prostate is performed with adequate
      expertise.

PMID- 7817161
TI  - Cytogenetics of prostate cancer. Consensus Conference on Diagnosis and Prognostic
      Parameters in Localized Prostate Cancer. Stockholm, Sweden, May 12-13, 1993.
AB  - This report summarizes the current knowledge with respect to genetic changes
      associated with the development of prostate cancer. The relation between the
      occurrence of these changes and the stage of the disease is by far not clear yet,
      albeit that some tendencies become more or less evident. In Fig. 2 these are
      summarized. Whereas changes on 7q and loss or gain of the X chromosome are not
      consistently found by either RFLP or ISH analysis, other changes are (8p-, 10p-,
      10q, 16q-, and 18q-). Clearly the picture is far from complete and even more the
      relevant genes on these chromosomes are not defined. E-cadherin was considered a
      good candidate and indeed the value as progression marker is great. However, the
      studies so far indicate that E-cadherin does not behave as a classical type I
      suppressor gene and the relation with 16q loss remains to be established. The
      data available to date regarding chromosomal changes in prostate cancer are
      limited. Many studies have to be pursued to identify the consistent changes, and
      moreover, to map the relevant loci harbouring the genes that are implicated in
      the development of this disease. This knowledge will be critical in the design of
      appropriate diagnostic methods and possibly clues towards therapy.

PMID- 7817162
TI  - Histopathology of localized prostate cancer. Consensus Conference on Diagnosis
      and Prognostic Parameters in Localized Prostate Cancer. Stockholm, Sweden, May 12
      13, 1993.
AB  - Future handling of patients with localized prostate cancer will undoubtedly
      depend upon a more sophisticated prognostication than that available today. The
      basis will continue to be the histopathological evaluation of tumor size, grade,
      localization and distribution within the gland. The aim of this section is to
      summarize current concepts of the morphological characteristics of localized
      prostate cancer and their prognostic implications as well as to give guidelines
      for standardization of the methods involved in morphological evaluation. First,
      baseline recommendations for the tissue processing procedures are given: Needle
      core biopsies, taken in a systematic way, potentially contain the information
      necessary for estimation of grade, size, distribution and extension to seminal
      vesicles, and could yield material for DNA-measurements, cytogenetic and genetic
      information. For TUR specimens it is suggested that at least 10 grams should be
      embedded or 8 to 10 cassettes employed minimally. The prostatectomy specimens
      should be carefully examined. Material should be frozen both from tumor tissue
      and from other areas eg by taking 'mapping' biopsies in a standardized way. After
      fixation (in 10% buffered formalin for at least 24 hours) and appropriate inking
      of surgical margins, whole mount sections at 2.5-5 mm intervals should be cut.
      The extension of the tumor should be outlined and at least the two largest tumors
      should be graded. Capsule penetration and extension to surgical margins and
      seminal vesicles should be indicated. Grading of malignancy should always include
      the Gleason grade and where possible Gleason score (ie the sum of the dominant
      and the secondary grade or pattern). The WHO and the Boecking systems combine a
      grading of glandular architecture with a grading of the nuclear atypia. It is
      stressed that in core biopsies the amount of cancer is sometimes scanty, which
      limits the possibility to find dominant and secondary patterns. In such cases, a
      grading of glandular differentiation and of nuclear grade seems rational. Also,
      for comparison with cytological grading, the WHO system is suitable, since in
      both cases both tissue differentiation and nuclear atypia are judged. The future
      need for objective techniques is recognized. Prostatectomy pathology includes
      important features with high correlation to postoperative prognosis: eg capsular
      penetration. The extent of capsular penetration and the extent of involvement of
      the surgical margins is of importance. Only focal penetration or focal
      involvement of the margin carry a relatively low risk of of progression.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7817163
TI  - Analgesic requirements for ESWL treatment. A double blind study.
AB  - This is a double blind study of the analgesic need during extracorporeal shock
      wave lithotripsy (ESWL) with a 2nd generation lithotriptor (Siemens Lithostar) in
      56 patients. A control group of 28 patients received 2 ml saline intravenously
      and 28 patients received 2 ml (0.1 mg) fentanyl intravenously before the start of
      treatment. Before ESWL all patients had subcutaneous infiltration with 20 ml
      lidocaine 1% and suppository naproxen 500 mg. Pain scores according to a visual
      analog scale (VAS) were recorded after 600 and 1000 shock waves and at the end of
      treatment. The patients were comparable with regard to age, sex, weight, number
      of shock waves given and duration of treatment. Pain scores and the need for
      supplementary analgesics were not significantly different between the two groups.
      We conclude that routine use of morphine is unnecessary during extracorporeal
      shock wave lithotripsy with Siemens Lithostar.

PMID- 7817164
TI  - Prognosis after nephrectomy for renal cell carcinoma.
AB  - During the period 1977-1988 177 males and 81 females (age 28-87 years) had
      nephrectomy performed for renal cell carcinoma. The most frequent symptoms were
      flank pain (54%) and hematuria (53%). Few patients (6%) had the classical triad
      of symptoms. Overall survival at 2 and 5 years were 0.55 and 0.41. Renal cell
      carcinoma specific survival were 0.59 and 0.49. Univariate analyses showed that
      increasing T stage, positive N or M stage, increasing stage according to Robson,
      hypersedimentation, anaemia and perioperative blood transfusion had a significant
      detrimental influence on survival. Multivariate analysis showed that simple
      Robson stage gave a simpler and equally good description as did the TNM stage. In
      the Cox multiple regression analysis Robson stage and ESR were the only
      statistically significant variables.

PMID- 7817165
TI  - Retroperitoneal fibrosis treated with methylprednisolon pulse and disease
      modifying antirheumatic drugs.
AB  - The conventional treatment of patients with ureteric obstruction due to
      retroperitoneal fibrosis (RF) is surgery in combination with long-term
      corticosteroids. This report describes 11 cases of RF with ureteric obstruction
      treated with methyl-prednisolon pulse therapy (MPPT) in combination with
      azathioprine or penicillamine following initial insertion of ureteral stents. The
      medial treatment suggested was successful in 7 patients, but only moderately
      effective in the last 4 patients. This principle of non-operative management of
      RF has not been previously reported.

PMID- 7817166
TI  - Biofeedback treatment of children and adults with idiopathic detrusor
      instability.
AB  - In adults and children suffering from urge, urge incontinence, frequent voidings,
      and nocturia, urodynamic examination often confirms the diagnosis of detrusor
      instability. We assessed the outcome of biofeedback therapy in 15 children aged 6
      12 years and 7 adults aged 20-52 years, all with cystometrically proven detrusor
      instability. The detrusor pressure was visually conveyed to the patient during
      repeated bladder fillings. The patient was instructed to interrupt detrusor
      pressure increments by tensing the pelvic floor musculature. None of the children
      were found completely cured; however, 9 showed a marked decrease in either the
      number of the extent of symptoms. Two children showed moderate improvement, while
      4 remained unaffected by the treatment. One adult was completely cured, 2
      improved moderately, and 4 showed no improvement. None of these patients were
      converted to stable cystometry. Upon termination of the BF treatment a follow-up
      study was conducted for patients exhibiting pronounced or moderate improvement.
      The beneficial effect was maintained except in one case.

PMID- 7817168
TI  - Morbidity of pelvic lymphadenectomy, radical retropubic prostatectomy and
      external radiotherapy in patients with localised prostatic cancer.
AB  - Staging pelvic lymphadenectomy (PLND) was performed in 210 prostatic cancer
      patients (mean age 67 years, clinical stage T0-T3 M0). A radical retropubic
      prostatectomy was subsequently performed in 54 men, ten of whom also received
      postoperative radiotherapy due to positive surgical margins. Ninety-eight
      patients were treated with external beam radiation alone (70 Gy in 35 fractions)
      and the remaining 58 received endocrine therapy. The complications of PLND alone
      (156 patients), consisted of wound infection in eight patients, hematoma or
      lymphocele in seven, venous thrombosis in three, and cardiac infarction in one
      patient. Early side-effects of radiotherapy included mild to moderate proctitis
      and/or cystitis in 57 patients. One year after completion of therapy, 48 of the
      irradiated men had proctitis, but only six had severe symptoms. Four patients
      developed radiation cystitis and two urethral stricture. Following prostatectomy
      (54 patients), two patients died in pulmonary embolism and another one developed
      a deep venous thrombosis. Hematoma occurred in five patients. Of the 42 surviving
      patients who did not receive postoperative radiotherapy, eight developed
      anastomotic strictures and four had severe stress incontinence. Only five were
      fully potent one year after surgery. Eight of the ten patients receiving
      radiotherapy after prostatectomy developed side-effects from the intestine and/or
      the urinary bladder. Two of them became totally incontinent. One developed a
      severe hemorrhagic cystitis necessitating urinary diversion. All ten were
      impotent after treatment.

PMID- 7817167
TI  - The effect of bilateral pudendal blockade on the adjunctive urethral closure
      forces in healthy females.
AB  - The effect of bilateral pudendal blockade on the urethral pressure and power
      generation during coughing and pelvic floor squeezing was evaluated in 10 healthy
      women. The measurements were carried out at the bladder neck, in the high
      pressure zone, and distally in the urethra before and after blockade. Strong
      adjunctive closure forces were demonstrated all along the urethra. They were
      significantly reduced by pudendal blockade except at the bladder neck during
      coughing. The results indicate that the pudendal innervated striated muscles
      contribute significantly to the adjunctively acting closure forces all along the
      female urethra, including the bladder neck. Some passive pressure transmission to
      the bladder neck seems to take place during stress episodes following pudendal
      blockade, but whether it occurs in healthy females remain uncertain. The findings
      following pudendal blockade, corroborate with those in stress incontinent women,
      and thereby support the concept that striated muscle weakness is of
      pathophysiological significance in stress urinary incontinence.

PMID- 7817169
TI  - Lymph leakage after staging pelvic lymphadenectomy for prostatic carcinoma with
      and without heparin prophylaxis.
AB  - The effect of heparin prophylaxis on lymph leakage and lymphocele formation was
      observed in a randomized, prospective, consecutive study of 48 patients
      undergoing lymph node dissection for staging carcinoma of the prostate.
      Subcutaneous low-dose heparin was given to 24 patients, and 24 without heparin
      prophylaxis constituted the control group. Lymph leakage per day was
      significantly greater and the leakage period longer in the heparin group than in
      the controls. The total of leaked lymph was notably greater and the incidence of
      lymphocele seven times higher in the heparin group than in the controls. All
      lymphoceles disappeared spontaneously in the first postoperative year. The
      results suggest high risk of prolonged lymph leakage and of lymphocele formation
      when low-dose heparin prophylaxis is given to patients undergoing a staging
      operation for prostatic carcinoma.

PMID- 7817170
TI  - Spermatic cord torsion in adults.
AB  - A five year retrospective review of 15 cases of spermatic cord torsion in male
      patients 18-years or older was performed. Eighty percent of patients were
      correctly diagnosed at time of initial presentation while 20% of patients were
      misdiagnosed as epididymitis. Fifty three percent of cases has history of similar
      previous attacks. The average delay prior to presentation was 7 hours. Absence of
      fever was the rule occurring in all patients. Leucocytosis and significant pyuria
      were commonly encountered occurring in 33% and 27% of patients respectively. Our
      orchidectomy rate was 20%. Our data suggest that while, in adult patients
      presenting with scrotal pain, the absence of pyuria make the diagnosis of
      epididymitis unlikely as a cause of the condition, the presence of significant
      pyuria even if associated with leucocytosis does not exclude spermatic cord
      torsion and further studies with Doppler examination and Radionuclide Scans are
      necessary to establish the diagnosis.

PMID- 7817171
TI  - Color Doppler sonography in the assessment of varicocele testis.
AB  - Color Doppler sonography is a new reliable and noninvasive diagnostic method in
      the evaluation of varicocele testes. Thirty-two persons (14 with varicoceles and
      18 controls) participated in the investigation. We found two different graphs
      (spectral analysis) in men with varicoceles testis during the Valsalva's
      manoeuvre. Semen analysis from these males with varicocele was compared with an
      age-matched control group without varicocele. The analysis revealed significant
      difference in qualitative motility and qualitative motility after 24 hours but no
      significant difference in other parameters of semen quality. There were
      significant difference in the normal semen morphology but no difference in
      abnormal forms among the two groups. We did not find a spectral picture that
      could predict a compromised sperm quality in the varicocele group. These data
      show that the color doppler is an important tool in the detection of a
      varicocele. It is important for the patient to understand the Valsalva's
      manoeuvre and we suggest that all males being evaluated in an infertility clinic
      undergo a color doppler scan with and without the Valsalva's manoeuvre and that a
      spectral analysis be performed to locate even small varicoceles.

PMID- 7817172
TI  - Double purpose penile skin flap one-stage urethroplasty for repair of distal
      penile hypospadias cripples.
AB  - A new one-stage urethroplasty operation is presented. The author called it
      "double purpose penile skin flap technique". It is recommended for the
      substitution of distal urethral defect when its length is equal to or less than
      half the circumference of the penile shaft in cases following multiple failed
      hypospadias repairs.

PMID- 7817174
TI  - Polycystic kidneys associated with Marfan syndrome in an adult.
AB  - A 41-year-old man with Marfan syndrome was found to have polycystic renal disease
      and underwent emergency surgery for dissecting aneurysm of the ascending aorta.
      To our knowledge only two cases of this rare combination of hereditary disorders
      have been described in the literature.

PMID- 7817173
TI  - Chronic renal failure: diagnostic measures before parathyroidectomy.
AB  - To investigate whether conventional criteria suffice to differentiate between
      hyperparathyroid and aluminum (Al)-related bone disease, we obtained bone
      biopsies from 7 patients with chronic renal failure (CRF) at the time of PTX and
      3.5-36 months later. All had hypercalcemia and elevated mid-region parathyroid
      hormone levels and 3 had bone pain at PTX. Bone histomorphometry revealed that 5
      patients had hyperparathyroid bone disease at PTX, while 2 had osteomalacia and
      skeletal Al deposits. Retrospective determination of intact PTH showed normal
      levels at PTX in the latter two. PTX effectively reduced all indices of
      parathyroid hyperactivity, but the two patients with Al-related bone lesions did
      not improve clinically nor histologically after PTX. Intact PTH and/or bone
      biopsy prior to PTX could have deterred surgery in those with Al-related bone
      disease.

PMID- 7817175
TI  - A tiny renal renin-secreting tumor.
AB  - A small 5 mm renal renin-secreting tumor is described in a child. Suggestions are
      made to circumvent the difficulties in investigating such cases. It is stressed
      that the diagnosis is probably often missed especially in the case of very small
      tumors.

PMID- 7817176
TI  - Giant adrenal myelolipoma. Report of a case and review of the literature.
AB  - The clinicopathologic features of a giant adrenal myelolipoma (diameter 16 cm,
      weight 900 g) are presented. The ultrasonographic and the computed tomographic
      appearance of adrenal myelolipoma are reviewed. Diagnostic fine-needle aspiration
      biopsy is recommended for avoidance of unnecessary surgical treatment.

PMID- 7817177
TI  - Infiltrating non-Hodgkin's presenting as acute renal failure.

PMID- 7817178
TI  - Mega total hip replacement after resection of metastasis from renal
      adenocarcinoma.
AB  - A 53-year-old man presented with femoral metastasis from a renal carcinoma. Four
      months after bone curettage and fixation and nephrectomy, a large recurrence of
      the metastasis was resected en bloc with the proximal femur and a megaprosthesis
      inserted. Six years later he is well and physically active.

PMID- 7817179
TI  - Nephrogenic ascites. Case report and review of the literature.
AB  - Nephrogenic ascites is a clinical diagnosis defined as persistent ascites in an
      uremic patient without evidence for a causative (specific) underlying disease.
      The incidence is not known. Contributing mechanisms may include peritoneal
      membrane changes, fluid overload, hyperparathyroidism, reduced lymphatic
      drainage, heart failure and hypoproteinemia. Rigid fluid control, intensive
      hemodialysis, high-protein diet, intravenous albumin infusion, intraperitoneal
      steroid injections and paracenteses as well as implantation of a peritoneatrial
      pump have all been found ineffective as treatment. Peritoneal dialysis has been
      shown to resolve ascites, however, the only effective treatment is so far renal
      transplantation. The development of nephrogenic ascites is associated with a poor
      prognosis. Thus, one year after the development of nephrogenic ascites 1/3 had
      died.

PMID- 7817180
TI  - Postrenal transplant urethral Kock pouch.
AB  - We report on a man with schistosomal bladder who developed stage T3N0M0, grade II
      transitional cell carcinoma of the bladder 9 years following successful renal
      transplantation. Radical cystoprostatectomy was performed and urethral Kock pouch
      was implanted in the same setting. The patient was continent and the graft
      function was maintained without reflux or obstruction at a follow-up period of 2
      years. No complications due to poor intestinal healing or intraabdominal sepsis
      were observed despite immunosuppression and electrolyte disorders were minor.

PMID- 7817181
TI  - A pelvic mass: bladder diverticulum with haemorrhage in Ehlers-Danlos patient.
AB  - We report on a case of haemorrhage in a large bladder diverticulum, impressing as
      a pelvic mass, in a patient with the Ehlers-Danlos syndrome. A review of the
      literature revealed 14 other cases of bladder diverticula and the Ehlers-Danlos
      Syndrome. Conservative treatment is first choice, unless complications occur.

PMID- 7817182
TI  - Spontaneous bladder rupture in association with carcinoma.
AB  - Spontaneous rupture of the bladder is very rare. Carcinomas are involved in a few
      procents of these ruptures. A case of spontaneous rupture through an area with
      transitional cell carcinoma in a female is presented along with a review of this
      rare condition.

PMID- 7817183
TI  - Paget's disease in a squamous metaplasia of the urinary bladder. The first
      published case of a disease which is usually found in the epidermis.
AB  - Extramammary Paget's disease is usually found in epidermis and is often
      associated with malignancy in visceral organs. We report the first case with
      Paget's disease developed in metaplastic squamous epithelium in the urinary
      bladder.

PMID- 7817184
TI  - Penile oedema induced by continuous condom catheter use and mimicking keloid
      scar.
AB  - Continuous use of condom catheter for urinary incontinence in a patient with
      neurogenic bladder gave rise to localized chronic oedema on the dorsum of the
      penis, mimicking keloid scar, and urethral fistula on the ventral surface. These
      unusual combined complications on the penile surfaces were due to pressure
      effect.

PMID- 7817185
TI  - Dangerous sex. New signs of risk taking prompt rethinking about AIDS prevention.

PMID- 7817186
TI  - Putting Alzheimer's to the tests. Several new techniques may detect the disease.

PMID- 7817187
TI  - Molecular machines that control genes.

PMID- 7817188
TI  - Manic-depressive illness and creativity.

PMID- 7817189
TI  - The history of synthetic testosterone.

PMID- 7817191
TI  - On the importance of prevention.

PMID- 7817190
TI  - Managed care dilemma.
AB  - The term, MANAGED CARE, is new to most physicians who were trained during the so
      called golden age of medicine. The various acronyms associated with this new era
      of medical care confuse even the young generation of physicians. This paper is
      written to identify the various players of managed care and to explain the
      differences between them. You can call this paper a glossary of the various HMOs
      that will be part of the new health care system.

PMID- 7817192
TI  - Molecular medicine: a primer for clinicians--Part VI: Introduction to genetic
      testing.
AB  - Application of the tools of molecular biology to clinical medicine is most
      apparent than in the development of DNA-based diagnostic and predictive tests.
      Such tests allow direct examination of the DNA of individuals for the presence or
      absence of the causative or predisposing molecular defect for a disease or
      condition. In this and the next two papers, in our series, we will discuss
      various aspects of genetic testing. We will consider the different types of
      testing, their current and potential clinical applications and discuss some of
      the major ethical and legal issues that genetic testing poses.

PMID- 7817193
TI  - Cancer pain management.

PMID- 7817194
TI  - [Osteosynthesis of femur shaft fractures with the unreamed AO-femur nail.
      Surgical technique and initial clinical results standard lock fixation].
AB  - Nailing technique has changed in recent years in some important aspects which are
      not limited to the omitted reaming procedure. These changes concern patient
      positioning, reduction technique and determination of implant length and
      diameter. Approach and exposure techniques have been modified to new, less
      invasive procedures, in order to fulfill technical, functional and aesthetic
      requirements. Techniques and tricks have been developed for avoidance of fragment
      diastasis, axial and torsional malalignment and leg length differences. Finally,
      simple algorithms have been elaborated for the management of bilateral femoral
      shaft or ipsilateral tibial shaft fractures and the number and location of
      locking bolts. These algorithms, techniques and procedures were developed in a
      series of 108 femoral shafts, which were stabilized wit the AO unreamed femoral
      nail (UFN) in a prospective study between 1991 and 1994. Of these, 39 cases with
      a mean follow-up of 19.3 (range 8-40) months after trauma were reviewed.
      Fractures were classified according to Muller (1990): 6 type A, 21 type B and 12
      type C. Closed soft tissue damage was classified according to our classification:
      C0/I, n = 14; CII, n = 15 (Tscherne 1982). Among 10 open fractures 4 were OI,
      4OII, 1OIIIA and 1OIIIB (Gustilo 1976). The major complications were breakage of
      locking bolts (n = 2), one nail breakage after 9 weeks and one case of osteitis.

PMID- 7817196
TI  - [Current status of surgical technique for unreamed nailing of tibial shaft
      fractures with the UTN (unreamed tibia nail)].
AB  - Nailing technique has changed in recent years in some important aspects which are
      not limited to the omitted reaming procedure. These changes concern patient
      positioning, reduction technique, the use of temporary stabilizers such as the
      'Pinless', and determination of implant length and diameter. Approach and
      exposure techniques have been modified to new, less invasive procedures, in order
      to fulfill technical, functional and aesthetic requirements. Techniques and
      tricks have been developed for avoidance of fragment diastasis and axial and
      torsional malalignment. Finally, simple algorithms are described for the
      management of large bone defects, bilateral tibia shaft or ipsilateral femoral
      shaft fractures, number and location of locking bolts, the 'when and how' of
      patient mobilization and load bearing, and primary and secondary dynamization.
      These algorithms, techniques and procedures were developed in a series of 152
      tibia shafts, which were stabilized with the AO unreamed tibia nail (UTN) in a
      prospective study between March 1989 and June 1994. Of these, 75 cases with a
      mean follow-up of 19.4 +/- 6.3 (range 11-37) months after trauma were reviewed.
      Fractures were classified according to Muller (1990): 14 type A, 37 type B and 24
      type C. Closed soft tissue damage was categorized according to our
      classification: C0/1, n = 5; C2, n = 12; C3, n = 9 (Tscherne 1982). Among 49 open
      fractures 8 were OI, 18 OII, 10 OIIIA and 13 OIIIB (Gustilo 1976). The main minor
      intraoperative complication was drill bit breakage (n = 10), most frequently at
      the proximal locking holes. The main postoperative complication was breakage of
      locking bolts (n = 16), mainly between weeks 6 and 20. Minor secondary
      reinterventions were, in most cases, secondary dynamization under local
      anaesthesia. Major reintervention were: soft tissue reconstructions (n = 5),
      isolated cancellous bone graft (n = 6), and change of treatment (n = 12). There
      were nine changes to a reamed nail, two changes, in very proximal fractures, to
      plate osteosyntheses. There were three deep infections. Mean time to union was
      23.9 weeks (range 10-48 weeks, n = 73); in two cases non-union was observed. The
      overall result was judged with the Karlstrom-Olerud score, which was applicable
      in 66 of 75 cases; excellent, n = 2; good, n = 22; satisfactory, n = 24; fair, n
      = 9; poor, n = 9. In the remaining nine cases no scoring was attempted because of
      severe injuries around the knee or ankle.

PMID- 7817195
TI  - [Osteosynthesis of proximal femoral fractures with the modular interlocking
      system of unreamed AO femoral intramedullary nail. Initial clinical results].
AB  - The unreamed femoral nail system (UFN) features highly versatile proximal
      interlocking options for the treatment of a wide range of femoral fracture
      patterns and combinations. Besides standard interlocking modes for diaphyseal
      fractures, special interlocking options for subtrochanteric fractures and
      ipsilateral neck/shaft fractures are available. Two aiming arms can be attached
      to the insertion handle of the nail in a modular fashion. The standard aiming arm
      is designed for transverse static or dynamic locking. The special aiming arm
      permits spiral blade, 130 degrees, and miss-a-nail interlocking. From August 1992
      to July 1994, in 10 out of 55 UFN implantations the special interlocking options
      were used. In 9 subtrochanteric fractures the spiral blade interlocking and in
      one ipsilateral neck/shaft fracture the miss-a-nail cancellous screw interlocking
      was applied. ASIF type A fractures with closed soft tissue damage prevailed.
      Fracture healing was uneventful and no implant complications or loss of reduction
      have been observed.

PMID- 7817197
TI  - [Biomechanical studies of 9 tibial interlocking nails in a bone-implant unit].
AB  - Various different interlocking intramedullary nail designs are now available for
      the tibia the designs resulting from a different approaches to achieving
      stability for fracture fixation. During recent years small-diameter unreamed
      interlocking nails have been developed. So far there are no data on stiffness of
      different nail designs that can justify the use of certain nail types. We
      compared different nail types in the bone-implant complex (BIC) with reference to
      stiffness under axial load, bending and torsion of the BIC. We simulated
      comminuted mid-shaft fractures by a 2-cm defect osteotomy in paired human cadaver
      tibiae. We fixed each tibia with one of nine different interlocking nails (AO
      Unreamed Tibial Nail 9 mm [UTN9], AO Unreamed Tibial Nail 8 mm [UTN8], Russell &
      Taylor Delta Tibial Nail 9 mm [RTD], Russell & Taylor Reconstruction Tibial Nail
      11 mm [RTR], Brooker & Wills Nail 11 mm [B-W], Grosse & Kempf Tibial Nail 11 mm
      [G-K], AO Universal Tibial Nail 11 mm [AOU], Klemm & Schellmann Tibial Nail 11 mm
      [K-S], Borner & Mattheck Tibial Nail 11 mm [B-M]) according to the manufacturers'
      recommendations. Each BIC was tested mechanically using a Zwick universal testing
      machine. Torque testing was performed with a maximum moment of 5 Nm in both
      directions. Maximum axial load was 1100 N. Four-point bending was done up to a
      moment of 66 Nm. For each implant bending and torque stiffness of the nail were
      calculated and compared with the test results obtained in the cadaver study. A P
      value less than 0.05 (least significance difference test, ANOVA) was considered
      significant.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7817198
TI  - [Computerized tomography measurement of torsion angle of the lower extremities].
AB  - The precise evaluation of post-traumatic deformities is indispensable when
      planning a corrective osteotomy. Torsional angles of the lower extremities of 186
      patients were measured using CT. The mean age of the studied population was 34
      years (18-80). It consisted of 131 men and 55 women. All patients had sustained a
      fracture of at least one of the leg's bony segments. The normal femoral (n = 293)
      inward torsion measured 23.47 degrees +/- 17.16 degrees (mean +/- 2 SD). Normal
      tibia (n = 263) outward torsion was 34.03 degrees +/- 17.22 degrees. The
      intraindividual torsional differences were not normally distributed. Normal
      femoral (n = 103) intraindividual torsional difference measured 11 degrees (95%
      percentile) and 15 degrees (99% percentile), with a median of 4 degrees. The
      tibiae (n = 76) showed a normal intraindividual torsional difference of 12
      degrees (95% percentile) and 15 degrees (99% percentile). Right tibiae showed a
      statistically significant greater outward rotation when compared to their left
      counterpart (P < 0.001). No correlation to sex could be established. Preoperative
      planning of a corrective osteotomy should include the geometric evaluation of all
      four bony segments of the leg. Intraindividual torsional differences must be
      considered. A corrective osteotomy appears to be unnecessary with a torsional
      difference smaller than 15 degrees in the femora and smaller than 15 degrees in
      the tibiae.

PMID- 7817199
TI  - A reference method for correlation of anatomic and functional brain images:
      validation and clinical application.
AB  - We describe a reference device that provides accurate correlation between
      anatomic and functional brain images. The reference device, which generates
      fiduciary reference points on sequential scan planes, is positioned adjacent to
      the canthomeatal line of the subject and held in place by a glasses-like
      framework anchored to the external auditory meatus. The reference system was
      tested on 17 subjects undergoing 99mTc hexamethylpropylene amine oxime
      ([99mTc]HMPAO) brain single-photon emission computed tomography (SPECT) and
      cranial computed tomography (CT) scans. The centers of the caudate nuclei,
      thalami, brain stem, and cerebellar vermis were identified independently on CT
      and SPECT. The average difference +/- 1 SD between structure locations (x, y, and
      z) on SPECT and CT were calculated as 1.86 +/- 1.5, 2.16 +/- 1.4, and 1.83 +/-
      1.9 mm, respectively. The clinical application of the method is showed by
      coregistration of images from SPECT to MRI. An example of sequential [99mTc]HMPAO
      brain SPECT scan sections precisely coregistered with MRI scan sections oriented
      parallel to and sequentially above the canthomeatal line illustrates the
      correlation between regional cerebral blood flow (rCBF) tracer activity on SPECT
      and normal anatomic structures. Test-retest activation paradigms in brain SPECT
      requires precise SPECT-to-SPECT image coregistration to evaluate changes in rCBF
      during activation. Precisely coregistered rest, 48-hour repeat rest [99mTc]HMPAO
      SPECT studies are shown to illustrate the normal intrasubject variability of
      tracer uptake. An example of the usefulness of image coregistration for
      evaluation of viable residual brain tumor and its application to tumor biopsy is
      presented. An example of developmental abnormalities identified by [99mTc]HMPAO
      brain SPECT is illustrated by a case of autistic disorder. An example of image
      coregistration in stroke and evaluation of cerebrovascular disease with Diamox
      (Lederle Laboratory Division, Pearl River, NY) cerebrovasculature stress testing
      is presented. The usefulness in epilepsy using a protocol whereby the tracer is
      injected during the ictal phase of seizure is presented. We conclude that the
      reference system provides an accurate, rapid, and noninvasive patient-specific
      method for correlating brain structure with brain function.

PMID- 7817200
TI  - Correlative imaging with monoclonal antibodies in colorectal, ovarian, and
      prostate cancer.
AB  - Monoclonal antibody (MoAb) imaging has contributed greatly to the diagnosis and
      staging of both colorectal and ovarian cancers, and recently has been tested in
      patients with prostate cancer. Anatomic imaging modalities such as computed
      tomography, ultrasound, and magnetic resonance imaging have deficiencies in
      imaging each of these cancers that can be complemented or overcome by using
      radioimmunoscintigraphy. The management of patients with colorectal cancer, in
      particular, has been aided by developments in immunoscintigraphy. The new, safe,
      and easy-to-prepare MoAbs make possible an effective form of colon and rectal
      cancer imaging that has been used for (1) staging primary colorectal tumors in
      presurgical patients, (2) determining extent of disease, (3) continuing
      surveillance of patients at risk for recurrence of disease, (4) managing patients
      with elevated carcinoembryonic antigen levels (even those with otherwise negative
      workup results), and (5) imaging for occult, disease in patients both before and
      after surgery. In ovarian cancer patients, MoAbs are promising as safe, sensitive
      imaging tools. The U.S. Food and Drug Administration has approved 111In satumomab
      pendetide (OncoScint CR/OV; Cytogen Corporation, Princeton, NJ) for use in
      imaging colorectal and ovarian cancer. Immunoscintigraphy is being refined and
      tested to locate bony and soft-tissue metastases in patients with prostate
      cancer. As both a complementary tool and, in some cases, the imaging modality of
      choice, MoAbs have proven to be safe, accurate imaging tools for many patients
      with cancer.

PMID- 7817201
TI  - Comparison of modalities to diagnose coronary artery disease.
AB  - The purpose of this review is to compare several modalities available for
      detection of coronary artery disease (CAD). We compare the clinical history,
      rest/exercise electrocardiogram (ECG), rest/stress left ventricular (LV) function
      by radionuclide or echocardiographic methods, myocardial perfusion imaging (MPI)
      by single photon emission computed tomography (SPECT) or positron emission
      tomography (PET), contrast coronary angiography, magnetic resonance imaging
      (MRI), spectroscopy (MRS) and angiography (MRA), and ultrafast cine computed
      tomography (UFCT) to assess LV function, myocardial perfusion, and coronary
      calcification. We compare the modalities by answering six questions: (1) Does the
      modality provide unique clinical information? (2) What is the observer error? (3)
      What are sensitivities and specificities to detect CAD? (4) What patient
      selection criteria should be applied for each modality? (5) What incremental
      benefit is obtained from one modality versus another modality? and (6) Where do
      the modalities fit in the overall scheme of diagnostic testing for CAD? PET MPI
      appears to be the best noninvasive test for CAD, followed by SPECT thallium-201
      and then dobutamine echocardiography. MRA and UFCT may soon play a larger role
      because they visualize the arteries. Contrast coronary angiography remains the
      gold standard despite its limitations. Exercise ECG is the least accurate test.
      The choice of tests critically depends on patient selection--based on clinical
      history, age, gender, and risk factors to estimate the pretest, clinical
      probability of CAD.

PMID- 7817202
TI  - Correlative image registration.
AB  - Image registration in nuclear medicine and radiology refers to the spatial
      matching or merging of two or more images from the same or different imaging
      modalities. The coordinates of the corresponding picture elements (pixels) from
      different images are transformed to align and equate their positions and spatial
      coordinates. Correlative image registration is a more restrictive term that
      applies to the matching of spatial coordinates of images coming from different
      imaging modalities. The registration of correlative images provides a useful
      approach to combine the best sensitivities and specificities of complementary
      procedures to detect, locate, monitor, and measure pathological and other
      physical changes. Here we review the registration of images from nuclear medicine
      (single-photon emission computed tomography, positron emission tomography and
      planar imaging) with those from other imaging modalities (magnetic resonance
      imaging, computed tomography, digital subtraction angiography and ultrasound) to
      closely correlate changes in metabolism, blood flow, receptor density, and other
      functional measurements with regional anatomy and morphological changes. The
      types of image registration applications, techniques, and terminology associated
      with image registration and examples of application are presented.

PMID- 7817203
TI  - Radiopharmaceuticals for brain imaging.
AB  - Brain imaging is performed using radiopharmaceuticals by single photon emission
      computed tomography (SPECT) and positron emission tomography (PET). SPECT and PET
      radiopharmaceuticals are classified according to blood-brain-barrier
      permeability, cerebral perfusion and metabolism receptor-binding, and antigen
      antibody binding. The blood-brain-barrier (BBB) SPECT agents, such as 99mTcO4-,
      [99mTc]DTPA, 201TI and [67Ga]citrate are excluded by normal brain cells, but
      enter into tumor cells because of altered BBB. These agents were used in the
      earlier period for the detection of brain tumors. SPECT perfusion agents such as
      [123I]IMP, [99mTc]HMPAO, [99mTc]ECD are lipophilic agents and therefore, diffuse
      into the normal brain. These tracers have been successfully used to detect
      various cerebrovascular diseases such as stroke, Parkinson disease, Huntington's
      disease, epilepsy, dementia, and psychiatric disorders. Xenon-133 and
      radiolabeled microspheres have been used for the measurement of cerebral blood
      flow (CBF). Important receptor-binding SPECT radiopharmaceuticals include
      [123I]QNE, [123I]IBZM, and [123I]iomazenil. These tracers bind to specific
      receptors in the brain, thus displaying their distribution in various receptor
      related cerebral diseases. Radioiodinated monoclonal antibodies were used for the
      detection of brain tumors. PET radiopharmaceuticals for brain imaging are
      commonly labeled with positron-emitters such as 11C, 13N, 15O, and 18F, although
      other radionuclides such as 82Rb, 62Cu and 68Ga also were used. The brain uptake
      of [13N]glutamate, [68Ga]EDTA and [82Rb]RbCl depends on the BBB permeability, but
      these are rarely used for brain imaging. Several cerebral perfusion agents have
      been introduced, of which [15O]water, [13N]ammonia, and [15O]butanol have been
      used more frequently. Regional CBF has been quantitated by using these tracers in
      normal and different cerebral disease states. Other perfusion agents include
      [15O]O2, [11C]CO, [11C]CO2, [18F]fluoromethane, [15O]O2, [11C]butanol, and
      [62Cu]PTSM. Among the PET cerebral metabolic agents, [18F]fluorodeoxyglucose
      (FDG) is most commonly used to detect metabolic abnormalities in the brain.
      Various brain tumors have been graded by [18F]FDG PET. This technique was used to
      detect epileptic foci by showing increased uptake in the foci during the ictal
      period and decreased uptake in the interictal period. Differentiation between
      recurrent tumors and radiation necrosis and the detection of Alzheimer's disease
      have been made successfully by [18F]FDG PET. Other PET metabolic agents such as
      [11C]deoxyglucose, and [11C]methylmethionine have drawn attention in the
      detection of brain tumors. [18F]fluorodopa is a cerebral neurotransmitter agent,
      which has been found very useful in the detection of Parkinson disease that shows
      reduced uptake of the tracer in the striatum of the brain.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 7817204
TI  - Sharp peaks in the downslope phase of the diuresis renogram.

PMID- 7817205
TI  - Myocardial perfusion defects resulting from conditions other than
      atherosclerosis.

PMID- 7817207
TI  - Patient trajectory: improving care for the radical retropubic patient.

PMID- 7817206
TI  - Writing about urology nursing.

PMID- 7817208
TI  - A qualitative approach to defining "hot flashes" in men.

PMID- 7817209
TI  - Endourologic diagnosis and conservative management of upper tract urothelial
      cancer.

PMID- 7817210
TI  - Future perspectives in urologic laparoscopy.

PMID- 7817211
TI  - Discontinued percutaneous nephrostomy tubes: how to keep patients dry.

PMID- 7817212
TI  - Testicular prosthesis: effect of the silicone controversy.

PMID- 7817213
TI  - A vertical disinfectant holder for urologic instruments.

PMID- 7817214
TI  - The medication minute.

PMID- 7817215
TI  - The role of the European Union in promoting healthy ageing.

PMID- 7817216
TI  - Agenda for an anthropology of pharmaceutical practice.
AB  - Over the last two decades, patterns of pharmaceutical-related behavior and the
      cultural interpretation of medicines have been examined by anthropologists in
      several cultural settings. In this paper the authors identify additional issues
      warranting study so as to broaden the scope of pharmaceutical anthropology,
      utilizing as a unifying focus the examination of pharmaceutical use in the
      context of social transformation. Ten interactive themes are presented which
      bridge micro-level and macro-level investigations of pharmaceutical use. The
      discussion moves from the discourse on 'rational drug use' to the rationales
      which underscore drug prescription, manufacture, and demand.

PMID- 7817217
TI  - The relationship of alcohol use to sexual activity in a U.S. national sample.
AB  - Recent reports have indicated that the use of alcohol is related to sexual
      behavior (such as unprotected intercourse) that is high-risk for HIV infection.
      However, most of these studies have collected data from convenience samples,
      using measures of varying specificity. This paper describes a study designed to
      investigate the relationship of alcohol use to unsafe sexual activity in a
      representative sample of adults. Data were collected from 2058 respondents as
      part of a survey of a multi-stage area probability sample of the adult household
      population of the 48 contiguous United States. The interview instrument included
      measures of alcohol use, sexual activity and condom use. Logistic regression
      analyses showed that heavier drinkers were more likely to be sexually active, and
      if sexually active, were more likely to have had more than one sexual partner in
      the previous year. However, drinking variables were in general not significantly
      related to condom use. These results suggest that alcohol use may be more
      strongly related to lifestyle variables (general sexual activity and number of
      sexual partners) than to more concrete behavioral variables such as condom use.
      Because these data are correlational, the findings are also consistent with the
      notion of a general constellation of risk-taking or sensation-seeking activities
      that includes alcohol use and sexual activity.

PMID- 7817218
TI  - Test-retest reliability of health state valuations collected with the EuroQol
      questionnaire.
AB  - This study is a contribution by the Dutch participants to the research programme
      of the EuroQol Group. This collaborative group of researchers engaged in outcome
      measurement is working towards the development of a standardized, non-disease
      specific instrument for describing and particularly valuing health-related
      quality of life. The present article analyses the test-retest reliability of the
      valuations collected with the EuroQol questionnaire in a population survey (n =
      208). The choice of the appropriate method for test-retest analysis is discussed
      and the results of several approaches with the EuroQol data are shown.
      Generalizability Theory is proposed as the most suitable method. This method is
      the most comprehensive, giving distinct information about the relative
      contributions of different sources of variance. The EuroQol valuations appear to
      have good test-retest reliability.

PMID- 7817219
TI  - Perceptions of menopause in northeast Thailand: contested meaning and practice.
AB  - This paper draws on data collected from village-based ethnographic research
      conducted in northeast Thailand in 1990-1991 and highlights the polarities and
      contradictions of perceptions of menopause that exist between village women and
      health personnel with whom these women interact. For village women until
      recently, the menopause has been regarded as a simple and natural biological
      event; for health professionals, it is consistently represented as a 'medical
      problem' indicating treatment. The paper highlights women's construction of
      menopause, and their recognition and management of its physical symptoms. It
      draws attention too to differences among women and to the dynamic nature of their
      understandings and consequent health-seeking behaviour. The paper also describes
      the way in which health providers, through their own training and reading of
      professional and popular journals, increasingly represent the menopause as a
      pathological process and treatable condition. Through the exploration of
      conflicting perceptions of the menopause among contemporary Thai women, the paper
      draws attention to the heterogeneity and fluidity in understandings of biological
      processes that are related to and reflect the wider social and economic changes
      to which they are subject.

PMID- 7817220
TI  - Psychological well-being of gay men with AIDS: contribution of positive and
      negative illness-related network interactions to depressive mood.
AB  - While the positive functions of social network interactions in ameliorating the
      effects of life stress are widely documented and acknowledged, a growing body of
      research investigations has demonstrated that social relationships can
      concurrently be a source of stress and that actions intended to be supportive may
      instead be experienced as psychologically disturbing. Data from a study of the
      social support experiences of gay men diagnosed with AIDS were examined to
      determine the contribution to the men's depressive mood of positive and negative
      network interactions (n = 83). Although the results are consistent with the
      social support literature regarding the beneficial effect of positive network
      interactions for seriously-ill individuals, the findings also indicate that
      negative illness-related network interactions are associated with decreases in
      depressive mood, as indicated by scores on the Center for Epidemiological Studies
      of Depression Scale (CES-D). The findings also demonstrate the additive effects
      of positive and negative network interactions and clearly point out the value of
      investigating the complexity and multiple functions of social interactions.

PMID- 7817221
TI  - HIV prevention education for lesbians and bisexual women: a cultural analysis of
      a community intervention.
AB  - AIDS is increasing almost four times as fast among women, yet lesbians and
      bisexual women are among the least studied, least understood and most elusive
      populations affected by the AIDS epidemic. This paper reports the results of
      community-level HIV prevention research designed: (a) to examine the knowledge,
      perceptions, social contingencies and political constraints affecting the HIV
      risk taking of lesbians and bisexual women; and (b) to offer them context
      specific HIV prevention education. The study was a peer educator-based
      intervention project situated in San Francisco's women's bars, dance clubs, and
      sex clubs to reach socially and sexually active lesbians and bisexual women in
      natural settings. Between June 1992 and May 1993, ethnographic interviews were
      conducted with 626 women attending the bars and clubs; group presentations at
      these locales reached 1,315 women. The structure of the intervention was
      effective in prompting interest in HIV prevention information and intent to
      change behavior. The resultant cultural analysis details risk behaviors lesbians
      and bisexual women participate in, myriad constraints they face in trying to
      enact safer behaviors, gaps in knowledge, difficulties comprehending the
      relevance of HIV prevention, and risk reduction strategies commonly employed.

PMID- 7817222
TI  - Behavioural change amongst drug injectors in Scottish prisons.
AB  - A study of injecting behaviour amongst a purposive sample of drug-users in
      Scottish prisons found that 32% reported injecting prior to current sentence. The
      percentage of these who were injecting during their current prison sentence (i.e.
      inside the prison) had fallen to 11%. Of those who were injecting prior to
      imprisonment, 24% reported sharing injecting equipment at that time. Of those who
      were still injecting in prison, however, 76% reported sharing equipment. Overall,
      therefore, there were fewer injectors in prison, but a higher proportion of these
      shared needles. Factors most closely identified with current sharing of injecting
      equipment in prison were: (a) having injected a wider range of drugs in prison
      (during both current and previous sentences); (b) frequency of Temgesic use; and
      (c) being prescribed methadone in the community, then having that prescription
      discontinued on entry to prison.

PMID- 7817223
TI  - WDHA (watery diarrhea, hypokalemia, achlorhydria) syndrome: clinical features,
      diagnosis, and treatment.
AB  - WDHA (watery diarrhea, hypokalemia, and achlorhydria) syndrome is an unusual
      paraneoplastic condition caused by excess vasoactive intestinal polypeptide (VIP)
      secreted by certain tumors. The onset of the syndrome is insidious, and diagnosis
      is usually delayed by months to years. Morbidity and mortality from untreated
      WDHA syndrome are related to long-standing dehydration and electrolyte and acid
      base disturbances resulting in chronic renal failure. Diagnosis requires
      documentation of large volumes of secretory diarrhea, elevated serum VIP levels,
      and localization of the VIP-secreting tumor. Treatment includes correction of
      volume, electrolyte, and metabolic abnormalities, pharmacotherapy to decrease
      gastrointestinal secretion and increase absorption, and ultimately surgical
      resection or debulking of the vipoma.

PMID- 7817224
TI  - Rationing health care: preparing for a new era.
AB  - As the American health care system struggles to provide universal access to
      quality care at an acceptable price, many planners focus on rationing as the only
      way to make available the necessary resources. I discuss some of the ethical,
      economic, and political issues that relate to health care rationing. The four
      important questions to consider when examining a rationing plan are: (1) Who acts
      as the gatekeeper? (2) What kinds of goods or services are rationed? (3) What
      happens to the money and resources that are saved by rationing? (4) Does the
      system provide a safety valve for the well-to-do? This article examines two
      prototypical rationing systems--the British system and the Oregon plan--and
      answers these four questions for both systems. Because of the absence of an
      efficient market economy in health care and the certainty of resource
      constraints, rationing is inevitable in American health care. The primary issues
      are whether rationing will be done implicitly or explicitly and whether it will
      be based primarily on ability to pay (as in the present system) or on comparative
      judgments about the costs and benefits of medical interventions.

PMID- 7817225
TI  - Nitric oxide: a selective pulmonary vasodilator.
AB  - Nitric oxide (NO) has recently been found to be the endothelium-derived factor
      that produces profound relaxation of the vascular smooth muscle. This discovery
      has led to the experimental use of inhaled NO as a selective pulmonary
      vasodilator without concomitant systemic vasodilation. Currently, clinical trials
      of inhaled NO in persistent pulmonary hypertension of the newborn (PPHN) are in
      progress. Inhaled NO has also been used in the adult respiratory distress
      syndrome (ARDS). The therapeutic role, if any, of inhaled NO in other diseases
      featuring pulmonary hypertension remains unknown. Further research is needed to
      determine potential toxic effects of NO, development of delivery systems, and
      monitoring techniques applicable to routine clinical care.

PMID- 7817226
TI  - Effects of aerobic exercise in normotensive adults: a brief meta-analytic review
      of controlled clinical trials.
AB  - The purpose of this study was to examine the effects of aerobic exercise on
      resting systolic and diastolic blood pressure in normotensive adults. The results
      of nine studies published in journals (1963 to 1992) and representing a total of
      438 subjects (289 exercise, 149 control) were statistically aggregated using the
      meta-analytic technique. Statistically significant reductions were found for both
      resting systolic and diastolic blood pressure (mean +/- SD, systolic, 3 +/- 3,
      95% confidence interval, 1.30 to 5.11; diastolic, 3 +/- 4, 95% confidence
      interval, 0.05 to 4.82). None of the changes were significant for the control
      groups. Absolute reductions corresponded with decreases of approximately 2% in
      resting systolic pressure and 4% in diastolic blood pressure. Significant
      correlations were found between changes in resting blood pressure and duration of
      training (systolic, r = .66; diastolic, r = .80, both at P < .05). The results of
      this study suggest that aerobic exercise results in small reductions on resting
      systolic and diastolic blood pressure among normotensive adults. However, such
      small reductions may not be clinically important. In addition, more meticulous
      studies on this topic are needed.

PMID- 7817227
TI  - Clinical experience with 180 inflatable penile prostheses.
AB  - I present my experience with 180 inflatable penile prostheses inserted in 167
      patients with organic sexual impotence of 4 months to 30 years in duration. Mean
      age was 59.3 years. Prostheses used were AMS 700 (9), Flexiflate (14), Mentor
      Mark II (99), and Mentor Alpha I (58). Mean follow-up was 43.5 months. Overall
      complication rate was 17.8% (32 cases). In 24 cases, the complications were major
      (infection, malfunction, and extrusion) and necessitated reoperation. The
      remaining complications (8 cases) were minor (partial deviation, autoinflation),
      and surgical intervention was not needed. Staphylococcus epidermidis was the
      offending microorganism in 7 of 9 infections. In general, my results with these
      penile prosthesis implants suggest that they are a valid form of treatment for
      organic impotence.

PMID- 7817228
TI  - Detection of problem drinkers: the Alcohol Use Disorders Identification Test
      (AUDIT).
AB  - This study was conducted to test the predictive validity of a new alcohol
      screening test, the Alcohol Use Disorders Identification Test (AUDIT), in a
      general medicine teaching clinic and to assess physician recognition and
      treatment of alcohol and drug disorders. The research procedures included
      completion of the AUDIT, a standardized diagnostic alcohol and drug assessment,
      an exit interview, and a chart review. The random sample comprised 132 recruited
      subjects. The internal reliability of the AUDIT was .77. The optimal cutoff score
      for the AUDIT in this sample was 5, with a sensitivity of .61 and specificity of
      .84. The exit interviews revealed that physicians asked their patients about
      alcohol use and drug use with 20% (n = 26) and 17% (n = 23) of the sample,
      respectively. Five of the 28 patients who met DSM-IIIR criteria had a diagnosis
      recorded in the chart.

PMID- 7817229
TI  - Appearance of drug-resistant tuberculosis in rural Tennessee.
AB  - Drug-resistant tuberculosis (DRTB) is a growing national health concern in both
      urban populations and rural areas and is exacerbated by the growing epidemic of
      human immunodeficiency virus (HIV) infection. Between 1989 and 1992, 7 cases of
      DRTB (5 with multidrug-resistance) were diagnosed in an eight-county region of
      East Tennessee. During 1990 and 1991 alone, 5 of 100 patients with tuberculosis
      had drug-resistant strains (5%). All 7 patients with DRTB had 100% resistance to
      isoniazid; 5 also had resistance to streptomycin, 2 to rifampin, and 1 to
      pyrazinamide and ethambutol. All patients were white, U.S.-born, and without
      evidence of HIV infection. Contact investigation revealed that more contacts of
      patients with DRTB (13 of 74, 18%) were infected than were contacts of patients
      with drug-sensitive tuberculosis (46 of 290, 16%). Our study demonstrates that
      DRTB is not confined to geographically distinct areas, but may be a subtle and
      easily missed diagnosis in presumably low-risk rural populations.

PMID- 7817230
TI  - Doppler echocardiographic assessment of valvular heart disease in patients
      requiring hemodialysis for end-stage renal disease.
AB  - Valvular heart disease accounts for considerable morbidity and some mortality
      among patients with end-stage renal disease (ESRD). To determine the prevalence
      and severity of valvular and perivalvular abnormalities, including valvular
      thickening, stenosis, calcification, regurgitation, and mitral annular
      calcification (MAC), and the impact of age and duration of dialysis on valvular
      disease in these patients, we reviewed Doppler echocardiograms in 75 consecutive
      patients requiring hemodialysis for ESRD. Our results showed that valvular
      sclerosis, calcification, and MAC were common in patients requiring hemodialysis;
      valvular regurgitation was both more prevalent and more severe in hemodialysis
      patients than in "normal subjects"; and age of the patient and duration of
      dialysis were related to the prevalence of valvular disease in ESRD. These
      findings suggest that Doppler echocardiography should be frequently used to
      assess possible valvular heart disease in patients receiving hemodialysis for
      ESRD, particularly older patients, those who have received dialysis for several
      years, and those with suspected valvular disease based on history and physical
      examinations.

PMID- 7817231
TI  - Missile injuries to the temporal bone.
AB  - Gunshot injuries to the head and neck are frequently seen in patients brought to
      a level I trauma center. These injuries result in great morbidity and mortality
      and a significant expenditure of health care dollars. Missile injuries to the
      temporal bone, though less common, can likewise be devastating. Common sequelae
      include vertigo, deafness, facial nerve paralysis, and death. A series of missile
      injuries to the temporal bone treated at Tampa General Hospital during 1993
      prompted a review of head and neck missile injuries in our trauma registry over
      the past 4 years (1989 to 1993). More than 100 patients were shot in the head or
      neck; 25 of them had injury to the temporal bone. Outcomes included facial nerve
      injury (8), deafness (9), vertigo (3), and death (13).

PMID- 7817232
TI  - Multiple myeloma after treatment of essential thrombocythemia.
AB  - An 83-year-old black woman with previously diagnosed essential thrombocythemia
      was treated with thiotepa to control the excessive number of platelets.
      Approximately 10 years later, multiple myeloma developed. This appears to be the
      first case of multiple myeloma occurring after alkylating agent therapy for
      essential thrombocythemia. Although the mechanism of the development of multiple
      myeloma has yet to be defined, continuing progress in cell biology may prove a
      strong association between multiple myeloma and other hematologic malignancies.

PMID- 7817233
TI  - Thrombotic thrombocytopenic purpura and HIV infection.
AB  - We report on a man who was HIV-seropositive and who was initially admitted
      following multiple episodes of syncope. He gradually developed fulminant
      thrombotic thrombocytopenic purpura (TTP). Twenty-one patients with TTP who were
      HIV-positive have been reported previously. Of these 22 patients, all treated
      with plasmapheresis, 7 died from TTP and 3 suffered relapse but eventually
      recovered. Delay in initiating plasmapheresis may be fatal. We have correlated
      the laboratory data of these patients at time of admission with subsequent
      clinical outcome; only the platelet count correlated with outcome. Patients with
      lower platelet counts were less likely to relapse or die with therapy. Physicians
      caring for patients infected with HIV should always consider the possibility of
      TTP in those patients with thrombocytopenia of unknown etiology. Review of the
      peripheral blood smear, allowing the detection of microangiopathic hemolytic
      anemia, is an important clue, enabling one to consider the correct diagnosis.

PMID- 7817234
TI  - Sunflower seed bezoar leading to fecal impaction.
AB  - We report the cases of two children, ages 8 and 10 years, with painful defecation
      and constipation due to impaction of sunflower seed shells that did not respond
      to laxative and enema therapy. Physical examination revealed a prickly mass in
      the rectal vault. Proctoscopy revealed bezoars of sunflower seed shells, which
      were removed by endoscopic biopsy forceps followed by a combination of rectal
      irrigation and manual disimpaction. The rectal pain resolved, and bowel habits
      returned to normal with laxatives. Patients with rectal bezoars who fail to
      respond to enemas or colonic lavage may require endoscopic management for
      resolution of their symptoms.

PMID- 7817235
TI  - Potency restored.

PMID- 7817236
TI  - Contingency-fee lawyers and the decline in DTP vaccinations.

PMID- 7817237
TI  - HIV and pulmonary hypertension.

PMID- 7817238
TI  - Poisonous snakes.

PMID- 7817239
TI  - "Historical cohort study of pedicle screw fixation in thoracic, lumbar, and
      sacral spine fusions".

PMID- 7817240
TI  - Degenerative lumbar spondylolisthesis. A meta-analysis of literature 1970-1993.

PMID- 7817241
TI  - Surgical treatment alternatives for fixation of unstable fractures of the
      thoracic and lumbar spine. A meta-analysis.

PMID- 7817242
TI  - Comprehensive literature review. Pedicle screw fixation devices.

PMID- 7817243
TI  - A Historical Cohort Study of Pedicle Screw Fixation in Thoracic, Lumbar, and
      Sacral Spinal Fusions.

PMID- 7817244
TI  - Review of the "Historical Cohort Study of Pedicle Screw Fixation in Thoracic,
      Lumbar, and Sacral Spinal Fusions" report.

PMID- 7817245
TI  - Spinal fusion: The use of bone screws in the vertebral pedicles. Summation.

PMID- 7817246
TI  - [Importance of close interdisciplinary cooperation in the treatment of diseases
      of the thyroid gland].
AB  - The authors reflect on the importance of interdisciplinary collaboration when
      resolving problems of the diagnosis and treatment of diseases of the thyroid
      gland. In 1989-1993 at the First Surgical Clinic of the Kosice Hospital 189
      patients were operated on account of thyroid disease. During the last year the
      number of operations increased substantially due to better cooperation. In their
      group eufunctional nodular goitre was indicated most frequently for surgery. In
      the diagnosis they preferred ultrasonography and needle aspiration cytology.
      Peroperative biopsy is used in every operation of the thyroid gland. If the USG
      and cytological finding are not clear, they perform hemothyroidectomy and send
      the material to a pathologist for evaluation. By intensive interdisciplinary
      collaboration they achieved a very low number of two-stage operations in
      carcinoma, 1.05% paralyses of the recurrent nerve and a 1.58% postoperative
      mortality.

PMID- 7817247
TI  - [Hepatic resection technique in children].
AB  - The authors present their experience with resection of the liver in children. In
      1986-1993 they performed a total of 34 major resections of the liver. The mean
      age of the operated children was 4 years and 5 months, the youngest patient was
      operated at the age of 4 days and the oldest one at the age of 17 years. The
      group was divided into two time periods which are compared, because in 1990 the
      authors changed their surgical tactics and technique and also the procedure used
      for general anaesthesia. During the first period/1986-1989/they made 12
      resections of the liver and during the second period/1990-1993/22 resections. The
      two groups of patients are compared as regards mortality during operation, early
      and late deaths. In the first period the mortality was 25%, in the second period
      no death occurred during operation. Early deaths were recorded during the first
      period in 25%, during the second period in 4.5%. Patient survival during the
      first period is 33% and during the second period 86.5%. The authors describe the
      technique of resection of the liver they use at present with emphasis on
      isolation of the vena cava inferior with the possibility of easier control of
      haemorrhage and the use of an ultrasonic aspirator/CUSA/and laser during
      resection proper which makes easier identification of hepatic structures and
      control of blood losses on operation possible. In malignant tumours the
      radicality of surgery increased as manifested on patient survival. From the first
      period 15% patients survive, from the second period 83% without signs of relapse.

PMID- 7817248
TI  - [Surgical experience with endoscopy in upper gastrointestinal tract hemorrhage].
AB  - During 1988-1994 at the Second Surgical Clinic in Brno and in the surgical
      department of the Hospital of Merciful Brethren in Valtice a total of 5200
      fibroscopic examinations were made incl. 560 on account of haemorrhage into the
      upper gastrointestinal tract. The purpose of fibroscopy was to detect sites of
      haemorrhage and treat them, or to establish at least the level of the
      haemorrhage. Visualization of the source was achieved in 90%, the level was
      assessed in 7.5% and failure was recorded in 2.5%. By treatment of the source of
      haemorrhage primary haemostasis was achieved in 83.32%, definitive haemostasis in
      77.01%. Endoscopy of acute haemorrhage into the GIT is at present the method of
      choice when resolving these conditions. Classical procedures involving
      supplementation of the blood volume and waiting for spontaneous haemostasis
      should be considered as "non lege artis" procedures.

PMID- 7817249
TI  - [Mesotheliomas].
AB  - The authors deal with the problem of mesotheliomas, their incidence and types.
      Most frequent are pleural mesotheliomas, which may be defined/localized/ or
      diffuse. Localized forms are indicated for surgery and have a favourable
      prognosis, diffuse forms are highly malignant and are considered a non-resectable
      malignity. The authors report on their own experience with a group of 47 patients
      with mesotheliomas. For diagnosis the part played thorocoscopy is significant.

PMID- 7817251
TI  - [Hemopurification methods in the surgical unit].
AB  - The authors submit their initial experience with the activities of the
      hemodialyzation centre at a surgical department. They present an analysis of 79
      patients where some hemopurifying procedures or their combinations were applied.
      These methods make it possible to perform more safely extensive surgery, they
      improve the care of patients with multiple injuries and extend therapeutic
      possibilities in acute pancreatitis and hyperbilirubinaemia when they cannot be
      treated by other methods. From the range of hemopurifying methods they consider
      the following most suitable for a surgical department: classical acute
      haemodialysis, hemodiafiltration, haemoperfusion and continuous arteriovenous
      dialysis.

PMID- 7817250
TI  - [Short-term prophylaxis with ceftriaxone in planned intrathoracic operations].
AB  - The purpose of the investigation was to evaluate the effect of short-term
      prophylaxis with a cephalosporin of the IIIrd generation, ceftriaxone, in 20
      patients with an elective intrathoracic operation. The investigation comprised
      patients operated on account of bronchogenic carcinoma, metastases in the lungs,
      relapsing spontaneous pneumothorax and carcinoma of the distal cesophagus.
      ceftriaxone - 1 g was administered before the introduction to anaesthesia. The
      second 1 g dose was administered after 12 hours. In addition to the
      microbiological examination of the bronchial secretion and evaluation of the
      minimal inhibitory concentration of ceftriaxone to the isolated bacteria the
      ceftriaxone serum level was assessed in the patients and its concentration in the
      pulmonary parenchyma. Postoperative inflammatory complications/pneumonia/ were
      detected in two patients. With regard to the long serum half-life/longer than
      surgery/ ceftriaxone is suitable for short-term prophylaxis in thoracic surgery.
      The serum level and ceftriaxone penetration into the pulmonary parenchyma is
      higher than the minimal inhibitory concentration in the majority of isolated
      bacteria.

PMID- 7817252
TI  - [Spontaneous pneumothorax--modern views on its therapy].
AB  - Based on a retrospective study the authors describe their experience with the
      treatment of spontaneous pneumothorax in 159 patients during a 5-year period/1989
      1992/. For the diagnosis they used, in addition to clinical and X-ray
      examination, in indicated cases also scintigraphy of the lungs, CT examination,
      thoracoscopy and bronchoscopy. During the period of investigation the basic
      therapeutic operation was thoracic drainage/one or several drains/, whereby in
      recent years there were more indications for surgery. Relapses were recorded
      after simple drainage in 46.5% of the patients, after surgery the authors did not
      record any relapses of spontaneous pneumothorax. Based on their own experience
      and data in the literature the authors recommend the radical approach to
      treatment of spontaneous pneumothorax using the least invasive videothoracoscopic
      technique which they have been using ever since 1993.

PMID- 7817253
TI  - [Aggressive angiomyxoma--a new clinico-pathologic entity].
AB  - The authors present a report on a new clinical and pathological entity-
      aggressive angiomyxoma which was described in 1983. They draw attention to the
      genesis of this tumour and its macro- and microscopic picture. They emphasize
      that treatment of this tumour involves its complete surgical extirpation and
      frequent local relapses without secondaries. The authors describe in detail two
      of their observations of aggressive angiomyxoma in a 32- an 38-year-old woman
      where the tumour started in the lesser pelvis. In both instances, despite radical
      extirpation of the tumour, within a relatively short time a local relapse
      developed detected by USG and CT without clinical symptoms.

PMID- 7817254
TI  - [From Murphy's button to Valtrac].
AB  - The author gives an account of the history of methods of mechanical compression
      viscerosynthesis without using sewing material and presents a report of the first
      clinical application of Valtrac on the territory of former Czechoslovakia.

PMID- 7817255
TI  - [Surgical treatment of esophageal reflux disease associated with a short
      esophagus].
AB  - Supradiaphragmatic fundoplication is effective therapy of complicated GER with a
      feasible morbidity and low mortality. These favourable results moreover do not
      apply to patients with primary oesophagitis but to a small percentage of patients
      suffering either from severe transmural oesophagitis or previous unsuccessful
      fundoplication. Under these conditions surgery is difficult regardless of the
      selected technique. An alternative possibility of supradiaphragmatic
      fundoplication in short oesophagus is Collis gastroplasty and fundoplication. The
      authors recorded good results of this operation/4, 12/. It may be, however,
      assumed that, at least in patients after previous fundoplication, mobilization of
      the oral portion of the stomach is associated either a further alteration of its
      blood supply and thus the risk of ischaemia of the "neo-oesophageal" suture.
      Supradiaphragmatic fundoplication is thus in the author's opinion the most
      effective therapeutic method in oesophagitis, performed on account of
      gastroesophageal reflux in short oesophagus.

PMID- 7817256
TI  - [Radiosurgery with the gamma knife].
AB  - The conception of radiosurgery now more than 40 years old is realized in clinical
      practice during last 25 years. There were elaborated 3 main methods: focused
      irradiation by gamma knife, by accelerated heavy charged particles and by linear
      accelerator. The results led radiosurgery spread over the world. The main
      indications are vascular malformations (44%), benign intracranial tumours (33%),
      malignant tumours including metastasis (21%) and functional disorders (2%). The
      pathological lesions can be controlled or liquidated in 80-95%. The hospital
      story is minimal, 1-2 days, and there is no risk of mortality and morbidity is
      minimal. Only the time of healing is prolonged to some years with indispensable
      follow-up. Further technical improvement and growing number of patients treated
      by radiosurgery can be expected.

PMID- 7817257
TI  - False-negative syphilis screening due to change in temperature.
AB  - BACKGROUND AND OBJECTIVES: Inaccurate test results for syphilis may cause an
      individual to experience serious effects. GOAL OF THE STUDY: Investigate
      potential sources of error and test limitations causing false-negative reactions.
      STUDY DESIGN: In 5 months, two laboratories screened 2,232 patients for syphilis
      by the Rapid Plasma Reagin (RPR) test. RESULTS: The hospital laboratory reported
      5.3% (64/1,210) of patients' test as reactive on initial screening, and the
      research laboratory found 6.4% (78/1,210) reactive. Fourteen reactive patients
      were incorrectly reported negative by the hospital laboratory, as confirmed by
      both laboratories. A refrigerated centrifuge in the hospital laboratory possibly
      caused sera to be cooled before testing, producing false-negative results. When
      its temperature was adjusted from 4 degrees C to 27 degrees C, an additional
      1,022 samples tested were consistent between the two laboratories. CONCLUSION:
      Cold temperature produces false-negative reactions for syphilis screenings in
      patients' samples with titers < 1:4 dilution. Patients' samples with titers > or
      = 1:16 dilution were not affected. According to this study, incorrect
      temperatures for test sera can alter testing outcomes. Therefore, test
      manufacturer's directions must be strictly followed.

PMID- 7817258
TI  - Characterization of the cytopathic effect of Haemophilus ducreyi.
AB  - BACKGROUND AND OBJECTIVES: Haemophilus ducreyi is the etiologic agent of
      chancroid, which is a genital ulcer disease that increases the risk of acquiring
      and transmitting HIV. The pathogenesis of H. ducreyi is not well understood. GOAL
      OF THIS STUDY: The goal of this study was to use a quantitative tetrazolium-based
      XTT assay to characterize the cytopathic effect of H. ducreyi on human foreskin
      fibroblasts. STUDY DESIGN: Haemophilus ducreyi strains 35000, R018, A77 and
      CIP542 were evaluated using the XTT assay. The role of attachment on resultant
      CPE was assessed using a wash step 2 hours post-infection. Internalization was
      evaluated by the gentamicin kill assay. Secreted exotoxin was studied using
      permeable inserts to separate the bacteria from the HFF monolayer. RESULTS: HFF
      cell damage did not appear to be mediated by a secreted H. ducreyi cytotoxin.
      Direct contact of viable H. ducreyi with HFF cells was required for cell damage.
      H. ducreyi strains that attached poorly could be readily removed by a wash step.
      This reduced their capacity to damage HFF cells significantly. Although some H.
      ducreyi strains attach to high levels within 4 hours, no HFF cell damage was
      detected by the XTT assay. However, once HFF cell damage was detected by 24
      hours, it was not easily reversible, despite antibiotic treatment that eradicated
      H. ducreyi. Internalization of H. ducreyi by HFF cells apparently did not occur
      to a significant degree. CONCLUSION: This study indicates that classic "soluble
      exotoxins" are not likely the key component in H. ducreyi pathogenesis.
      Attachment or direct contact with HFF cells are required for H. ducreyi to cause
      a CPE.

PMID- 7817259
TI  - Incidence and risk factors for acquisition of sexually transmitted diseases in
      heterosexuals with multiple partners.
AB  - BACKGROUND AND OBJECTIVES: The incidence of four STDs that are mainly transmitted
      during vaginal intercourse, and risk factors for acquisition during follow-up
      were studied in a cohort of heterosexuals with multiple partners in Amsterdam,
      the Netherlands. These heterosexuals with > or = 5 different sexual partners in
      the preceding 6 months were recruited from an STD clinic and participated
      voluntarily in a longitudinal HIV study between 1987 and 1991. STUDY DESIGN:
      Using survival techniques, the authors analyzed data on general characteristics,
      sexual behavior, reported and diagnosed STDs of 155 men and 234 women
      participating at least twice in the HIV study and returning regularly. RESULTS:
      The majority of women were prostitutes and the majority of men were clients of
      prostitutes. For men and women, the 2-year cumulative incidence were 2.7% (95%
      confidence interval [95% CI] 0.9-8.3) and 0.8% (95% CI 0.1-5.8), respectively,
      for syphilis, 8.5% (95% CI 3.9-18.0) and 5.3% (95% CI 2.6-10.8) for gonorrhea,
      20.2% (95% CI 12.5-31.9) and 31.9% (95% CI 23.7-42.2) for Chlamydia trachomatis
      infection, and 24.5% (95% CI 17.3-34.2) for trichomoniasis (examination in women
      only). Among men, STD(s) diagnosed at entry was found to be an independent
      predictor of infection with any of these STDs during follow-up (relative hazard
      (RH) = 2.58, 95% CI 1.18-5.64). Among women, risk factors were age < or = 25
      years (RH = 1.82, 95% CI 1.13-2.19) and current report of commercial unprotected
      vaginal contacts (RH = 2.19, 95% CI 1.11-4.13). Among women, trichomoniasis
      during follow-up was predicted by current report of commercial contacts (RH =
      2.59, 95% CI 1.16-5.79). C. trachomatis infection in women was associated with
      native country outside the Netherlands (RH = 2.47, 95% CI 1.38-4.43), reported
      history of STDs in the 4 months before the study (RH = 2.92, 95% CI 1.39-6.14)
      and age < or = 25 years (RH = 1.90, 95% CI 1.06-3.40). CONCLUSIONS: This study
      shows that STDs were common among this group of heterosexuals, despite regularly
      participating in the HIV study in which consistent condom use was promoted.
      Prevention efforts should be intensified for men and women having commercial
      sexual contacts, young women, and individuals with a history of STDs.

PMID- 7817260
TI  - Diagnosis of male Chlamydia trachomatis urethritis by polymerase chain reaction.
AB  - BACKGROUND AND OBJECTIVES: A quick and highly sensitive diagnostic test would be
      valuable in the diagnosis of Chlamydia trachomatis. GOAL OF THIS STUDY: We
      compared a new polymerase chain reaction (PCR) technique to Chlamydiazyme
      (Abbott, North Chicago, IL) in the detection of male chlamydial urethritis, and
      evaluated the performance of PCR on urine samples. STUDY DESIGN: Urethral samples
      for analysis by PCR and Chlamydiazyme were obtained from 474 unselected patients
      attending a sexually transmitted diseases (STD) clinic. Urine samples were
      analyzed by PCR from 362 of these patients. RESULTS: Twenty seven (5.7%) urethral
      samples were positive by Chlamydiazyme, while 64 (13.5%) were positive by PCR.
      After resolution of discrepant results, the sensitivity of PCR on urethral swabs
      was 98.4% and the specificity was 99.0%, with positive and negative predictive
      values of 93.8% and 99.8%, respectively. These same measures for Chlamydiazyme
      were 43.5%, 100%, 100%, and 92.2%, respectively. The sensitivity of PCR on urine
      samples was 87.1%, the specificity was 98.0%, and the positive and negative
      predictive values were 90.0% and 97.4%, respectively. CONCLUSIONS: This PCR test
      is more sensitive than Chlamydiazyme in detecting male urethral chlamydial
      infections in an STD clinic population, and appears to be equally efficacious on
      urethral swabs and urine samples.

PMID- 7817261
TI  - Clinical course and prognostic factors of human papillomavirus infections in men.
AB  - BACKGROUND AND OBJECTIVES: Biological behavior of male genital human
      papillomavirus (HPV) infection is incompletely understood, and the clinical value
      of treatment is obscure. GOAL OF THIS STUDY: To evaluate the clinical course and
      possible prognostic factors of genital HPV infections in men. STUDY DESIGN: A
      total of 318 consecutive high-risk men for HPV infection (94.3% partners of HPV
      infected women) were examined using peniscopy, histology, cytology, and in situ
      hybridization (ISH). Only the men with exophytic warts or clinical symptoms were
      treated, if they insisted on it (n = 55). The others with (n = 150) or without (n
      = 113) HPV suggestive lesions were followed-up only at 6-month intervals.
      Survival analysis was used to calculate the cure rates in different subgroups of
      the males, categorized according to the potential prognostic factors (i.e., age,
      treatment, lesion morphology, HPV type, female findings, and sexual habits).
      RESULTS: The calculated median cure time of the HPV-positive men was 15.2 months
      (95% confidence interval 12.2-21.3 months) and it did not differ significantly in
      the male groups treated or only followed-up (P = 0.56). In univariate survival
      analysis, only the ISH-positivity (P = 0.002) and the anamnestic use of condom (P
      = 0.05) were significant prognostic factors. The condom use also had a protective
      effect (P = 0.04) against the appearance of new HPV-suggestive lesions in
      initially healthy males. Although the treatment did not significantly affect the
      overall cure rate, the number of lesions decreased, however, after therapy (i.e.,
      fewer widespread infections), and the appearance of new HPV lesions seemed to be
      less frequent in the treated than in nontreated males. CONCLUSIONS: The low
      success rate of therapy and the obviously benign clinical course of all
      subclinical HPV lesions of the male genitalia justify the follow-up of all
      lesions with HPV-suspicious morphology only. On the other hand, treatment seems
      to exert a favorable effect on clinical HPV infections, new exophytic warts and
      penile intraepithelial lesions (PIN) lesions being rare in adequately treated
      males.

PMID- 7817262
TI  - Seroepidemiological studies of Haemophilus ducreyi infection in Ethiopian women.
AB  - BACKGROUND AND OBJECTIVES: To measure prevalence of anti-Haemophilus ducreyi
      antibodies in sera from Ethiopian female attendees, and to determine significant
      socioeconomic associations. STUDY DESIGN: A modified ELISA immunoassay was used
      to test sera of 1,831 Ethiopian women attending gynecological, obstetric, and
      family planning clinics in Addis Ababa. RESULTS: Overall seropositivity was
      19.4%. Prevalence rates for seropositivity for antibodies to H. ducreyi were
      significantly associated with ethnic group and religion, older age (> or = 50
      years: 28%), early age at first coitus (< 13 years: 28%) and first coitus before
      the menarche (25%), being divorced (27%) or a prostitute (24%), longer duration
      of marriage (> 20 years: 27%) and sexual life (> 20 years: 24%), number of
      lifetime sexual partners (2 to 5 partners: 27%) and self-reported history of both
      syphilis and gonorrhea (31%). Of these factors, the two most significant were
      first coitus before the menarche (P < 0.0001) and not being still married to the
      first husband/sexual partner (P < 0.001). Differences in seropositivity according
      to ethnic group and religion may be explained by the number of women within each
      group who had only one lifetime sexual partner. Women with serological evidence
      of exposure to another sexually transmitted disease (STD) had a greater risk of
      exposure to H. ducreyi. The odds ratio for H. ducreyi seropositivity in women
      with syphilis or gonorrhea was 3.6, for women with genital chlamydial infection,
      2.3, and for those with HBV or HSV-2, 1.4 and 1.3 respectively. CONCLUSIONS: This
      study illustrates the usefulness of the modified ELISA immunoassay for measuring
      exposure to H. ducreyi, and the usefulness of H. ducreyi as a marker for
      cumulative sexual exposure. Further studies on the association of HIV
      transmission and H. ducreyi in Ethiopia are now indicated.

PMID- 7817263
TI  - The impact of eliminating sterility on population growth.

PMID- 7817264
TI  - Hepatitis C virus infection among patients attending a clinic for sexually
      transmitted diseases in Paris, France: report on 470 patients.

PMID- 7817265
TI  - Recent trends in teenage childbearing in the United States.
AB  - Teen births and birth rates in the United States remain high. More than half a
      million American teenagers had babies in 1991. The birth rate for teenagers had
      fallen and stabilized between 1970 and 1986, but then increased 24 percent from
      1986 to 1991, to 62.1 births per 1,000 women aged 15-19. The vast majority of
      teen childbearing is unintended. The negative consequences of teen childbearing
      are severe. Teen mothers have greatly restricted educational attainment and are
      more likely to face lifetime poverty. They are less likely to receive timely
      prenatal care, and they have higher rates for certain risk factors for poor
      pregnancy outcome, such as inadequate weight gain and smoking during pregnancy.
      Their babies are at elevated risk of low birthweight and preterm birth, which in
      turn places them at risk for illness, developmental delays and even death.

PMID- 7817266
TI  - Outlook for U.S. population growth.
AB  - Between 1990 and 2020 the number of Americans is projected to increase by
      approximately 31 percent or to 325.9 million. However, gains among the various
      racial groups will differ markedly. The Asian-American population is expected to
      more than double while both whites and African Americans will have gains of less
      than 50 percent. During this period the number of whites as a percentage of the
      total population is projected to decline from 84 to 78 percent. Changes in state
      populations may be influenced by disparities in racial growth patterns. Those in
      the South and the West are expected to continue to growth at the expense of
      states in the Northeast and Midwest. Particularly rapid gains are forecast for
      the states of the Pacific and Mountain divisions. By 2020 it is expected that
      nearly 50 million persons will live in California, Texas will have 25.6 million
      inhabitants, Florida 19.5 million. The largest percent changes in the U.S.
      resident population between 1990 and 2020 will be in those persons over age 44.
      The largest relative increase (126 percent) is expected to be among persons aged
      85 and older.

PMID- 7817267
TI  - Vaccine-preventable illness in U.S. children 1980-1992.
AB  - For at least a decade after the licensure of vaccines to prevent major childhood
      diseases, incidence of these diseases decreased. However, in the mid-to-late
      1980s, four major childhood illnesses showed increases in the number of cases and
      the case rate, and the United States experienced epidemics of measles, mumps,
      rubella and whooping cough. The measles epidemic was the most severe of the four
      with over 55,000 cases, 11,000 hospitalizations, and 130 deaths reported across
      the country between 1989 and 1991. Children were hit the hardest by these
      epidemics. Predating these epidemics was a decline in the immunization levels of
      2-year-olds. This decline coincided with vaccine price increases, an increase in
      the percentage of children in poverty and a decline in the rate of poor children
      receiving Aid to Families with Dependent Children (AFDC) and Medicaid. An
      estimated 100,000 excess cases of disease resulted from the low levels of
      immunization and consequent epidemics. While immunization rates have increased in
      recent years, it is important to continue our progress in this area in order to
      protect children from vaccine-preventable infectious diseases.

PMID- 7817268
TI  - Average charges for uncomplicated cesarean and vaginal deliveries, United States,
      1993.
AB  - During 1993, average charges for a cesarean birth among MetLife group health
      insureds and dependents was $11,000 in comparison to $6,430 for women who had an
      uncomplicated vaginal delivery. Among the 34 states with at least 50
      uncomplicated cesarean births, the average total charge ranged from highs of
      $13,700 in New York and $13,480 in California to lows of $7,730 in Oklahoma and
      $8,270 in Ohio. Among the states with at least 100 vaginal births, New York again
      reported the highest average total charge ($8,840)--a charge 2.1 times the lowest
      reported charge in Arkansas ($4,190). The hospital charges (room and board plus
      ancillary fees) accounted for 63 percent of the total charges billed to MetLife
      for a cesarean delivery and 57 percent for a vaginal birth. Physician fees
      averaged $4,070 for a cesarean and $2,740 for a vaginal birth across the country;
      New York reported the highest charges for both types of deliveries, $6,680 and
      $4,710, respectively. Minnesota reported the lowest physician charges--$2,370 for
      a cesarean birth and $1,390 for an uncomplicated vaginal delivery. Hospital stays
      averaged 3.4 days for a cesarean delivery and 1.9 for a vaginal birth. Room and
      board charges accounted for 34 percent of the hospital charges associated with a
      cesarean birth and 37 percent for an uncomplicated vaginal birth.

PMID- 7817269
TI  - [The effects of low radiation doses: carcinogenesis].
AB  - In the low dose range such radiation risks, cf. the induction of cancer, have to
      be considered for which the lack of a threshold dose is assumed. The most
      important epidemiological data for cancer risk after irradiation come from the
      survivors in Hiroshima and Nagasaki. In the dose range below 100 mSv no increase
      of cancer rate can be observed in the total population with all age groups.
      Therefore the risk has to be estimated in the low dose range by extrapolation.
      Experimental studies of the mechanism of carcinogenesis have to clarify the
      question of a threshold dose. The variability of individual radiosensitivity is
      of great significance. After radiation exposures certain patterns of damage have
      been observed on the DNA. These phenomena may open the possibility to better
      recognize radiation-induced tumors in the low dose range.

PMID- 7817270
TI  - [Accelerated hyperfractionated radiotherapy combined with simultaneous
      chemotherapy in locally advanced pharyngeal and oral carcinomas].
AB  - PURPOSE: To evaluate the feasibility and effectiveness of a concurrent radio
      chemotherapy regimen for locally advanced carcinomas of the pharynx and floor of
      the mouth. PATIENTS AND METHODS: Since January 1990, 97 patients with locally
      advanced carcinomas of the naso-, oro-, hypopharynx and the oral cavity in UICC
      stages III and IV were treated according to an accelerated hyperfractionated
      radiotherapy schedule with concurrent chemotherapy. The primary tumor and
      positive lymph nodes received a total dose of 72 Gy in 6 weeks. In the first 3
      weeks, large fields were irradiated 5 times per week with 2 Gy per fraction.
      Thereafter, treatment was accelerated, giving 2 daily fractions of 1.4 Gy with
      minimal intervals of 6 hours. Target volumes were reduced after 49.6 and 59.4 Gy,
      excluding clinically uninvolved lymph node regions of low and high risk. On day
      1, 350 mg/m2 5-FU and 50 mg/m2 folinic acid were given as intravenous bolus
      followed by continuous infusion of 350 mg/m2 5-FU and 100 mg/m2 folinic acid,
      days 1 to 5. 10 mg/m2 mitomycin C was given on day 5 and 36 of the treatment.
      Salvage surgery was offered for residual disease 5 to 6 weeks after the end of
      radiotherapy. PATIENT CHARACTERISTICS: 70 male, 27 female; age: 27 to 81 years;
      T2/T3/T4: 7/30/60; N0/N1/N2/N3: 20/18/53/6;
      nasopharynx/oropharynx/hypopharynx/oral cavity: 16/33/36/12. Median follow-up is
      26 months. RESULTS: Overall survival and recurrence-free survival at 2 years were
      RESULTS: Overall survival and recurrence-free survival at 2 years were 68 +/- 5%
      and 74 +/- 5%. Multivariate analysis revealed a significant influence of the
      geometric mean neck node diameter or the N-stage on loco-regional control and
      survival. T-stage, tumor volume, or tumor localisation did not become
      significant. Acute toxicity of this schedule was acceptable but required
      optimised supportive care. Treatment related grade 4+ late toxicity of mucosa,
      soft tissue and bone were observed with a cumulative frequency of 13% at 2 years.
      Two patients died during a phase of severe leuko- or thrombocytopenia.
      CONCLUSION: This phase I to II trial shows favourable results using an
      intensified treatment radio-chemotherapy protocol. A phase III study is now
      planned, comparing this regime with an accelerated hyperfractionated radio
      therapy alone to an increased total dose of 77.6 Gy.

PMID- 7817271
TI  - [Hypoxic radiotherapy. The radioprotective effect of acute hypoxia in the
      radiotherapy of tumors in the abdominal area].
AB  - AIM: We tested, whether inhalation a of gas mixture containing 8.0 to 8.5% O2
      reduces the radiosensitivity of healthy tissue in order to deliver higher tumor
      doses without increasing the side effects of radiation therapy. PATIENTS AND
      METHODS: In this study 165 patients were treated in the Clinic of Radiation
      Oncology Erlangen (Germany) and in the Institute of Oncology in Brno (Czech
      Republic) in the period of January 1986 to December 1993. In 108 patients
      external irradiation was applied using acute hypoxia (group A-
      hypoxyradiotherapy). This group was compared with a conventional therapy group of
      57 patients (group B). The majority of the patients had advanced tumor of cervix
      uteri or of rectum. In 89% of patients of group A and in 61% patients of group B
      external irradiation was applied with portals > 20 x 15 cm2 (p < 0.01). The mean
      dose in the group A was increased about 30% compared to the mean dose of group B
      (55.2 Gy vs. 43.6 Gy; p < 0.01). RESULTS: Despite this increase in dose and large
      field irradiation in most cases in group A no differences were found between
      group A and B concerning acute or late effects of radiation therapy. CONCLUSION:
      The aerogen acute hypoxia (hypoxyradiotherapy) is so far not only the simplest,
      but also one of the most effective selective radioprotective methods.

PMID- 7817273
TI  - [Whole-brain irradiation with a central eye block and asymmetrical collimation].
AB  - BACKGROUND: In the treatment of multiple brain metastases, it is recommendable to
      irradiate the whole brain including temporal lobe and lamina cribrosa, but not
      the eye lenses. The disadvantage of former techniques using simple right-angled
      opposing lateral fields and further using individual blocks and positioning masks
      will be demonstrated and a new technique presented. METHODS: Without simulation,
      the patient's head will be positioned on the accelerator table so that the
      horizontal room laser touches the corners of the eyelids. By isocentric
      adjustment of the gantry angle to 90 degrees or 270 degrees, the eye lenses can
      be protected by a round shielding block which is placed in the central beam. The
      4 collimators are separate adjusted, beginning with the caudal field border,
      which extends from the lower orbita to the incisura intertragica, and proceeding
      with the other 3 collimators corresponding to the head outline. Preliminary
      irradiation portal film reveals the described target volume. The isocentric
      irradiation of the opposing field is arranged by mirror imaged input of the field
      parameters without changing the block. RESULTS: This technique allows a daily
      good reproducible irradiation of the whole brain including temporal lobe and
      lamina cribrosa by optimum protection of the eye lenses. The elimination of
      simulation, individual blocks and positioning masks and the practice of using
      only one block for the isocentric irradiation from both sides and for all
      patients is time saving and economical. CONCLUSION: The described technique is
      extremely simple, can easily be reproduced and creates an immediate total brain
      irradiation without compromise in the target volume under optimum lens
      protection.

PMID- 7817272
TI  - [The fulminant meningeosis blastomatosa of a medulloblastoma during postoperative
      chemotherapy].
AB  - BACKGROUND: Chemotherapy is currently investigated in young children with
      medulloblastoma with the objective to omit or even delay craniospinal
      irradiation. CASE REPORT: We report a case of very early meningeal progression of
      medulloblastoma during postoperative chemotherapy in a 2.5-year-old boy. At 2
      3/12 years of age, the boy developed ataxia. One month later, a malignant
      cerebellar tumor was diagnosed by magnetic resonance tomography. The boy
      underwent a macroscopically complete resection. Histological diagnosis revealed
      medulloblastoma. Postoperative magnetic resonance scans showed no residual
      disease or spinal seedings and the patient was classified as T3 M0 according to
      Chang. Three weeks after surgery, chemotherapy with ifosfamide, VP 16, and
      methotrexate was started. One month later, a positive Babinski sign developed,
      computed tomography scans showed no abnormalities. Chemotherapy was continued
      with cisplatin plus cytosine arabinoside as well as cisplatin plus ifosfamide and
      methotrexate. After 4 months of chemotherapy, a seizure and weakness of the legs
      occurred. Magnetic resonance scans revealed massive meningeal seeding and 400
      tumor cells/microliters were found in the cerebrospinal fluid. Craniospinal
      irradiation was initiated, and the neurologic symptoms resolved. The boy died,
      however, 4 months later due to progressive spinal disease. CONCLUSIONS: The early
      and rapid meningeal progression during chemotherapy is uncommon. The case
      demonstrates the difficulties of diagnosis and differential diagnosis.

PMID- 7817275
TI  - [The lymphogenic metastatic pathways of thoracic esophageal carcinoma--their
      clinical and prognostic significance].

PMID- 7817274
TI  - [Video technology and the personal computer in the therapy simulator].
AB  - PURPOSE: Technical progress in the development of radiation therapy simulators
      provided valuable addition of electronically stored images and monitor indicators
      for individual radiation parameters. One can store as well as print these data as
      a treatment plan. The possibility of supplementing older simulators with these
      technical options will be reported in the following paper. METHODS: The
      modification of our simulator installation was done simply. The new equipment
      needed to expand our simulator facility was almost exclusively derived from the
      fields of entertainment and home electronics (Visualizer/video camera, video tape
      recorder, video mixer, additional monitor; personal computer and printer).
      RESULTS: With these modifications we reached the technical standards of the
      latest simulator generation. In addition, we succeeded in implementing additional
      technical options: e.g. image inversion with contrast alignment to diagnostic
      displays, complete magnetic tape recording of the entire x-ray process with
      possible repetition, electronic overlapping of the simulator image and the
      diagnostic image (e.g. NMR; angiograms) to determine the treatment volume,
      automation in x-ray documentation. CONCLUSION: Increased precision and rational
      work steps employing readily available equipment will lead to further improvement
      in the quality of radiotherapy.

PMID- 7817276
TI  - [Preoperative low-dose-rate brachytherapy in cervix carcinoma: acute side effects
      in relation to the dosage rate].

PMID- 7817277
TI  - [Oral contraceptives and the prognosis in breast cancer].

PMID- 7817278
TI  - [Overweight and the malignoma risk].

PMID- 7817279
TI  - [The role of proto-oncogene expression in cellular radiosensitivity and
      radioresistance].

PMID- 7817281
TI  - [Access to documents--description and reason].

PMID- 7817280
TI  - [Norway--we want to have the same salary as men now. Interview by Grethe
      Kjaergaard].

PMID- 7817282
TI  - [A harsh reality].

PMID- 7817283
TI  - [Teamwork with volunteers--baby-sitters with a diploma].

PMID- 7817284
TI  - [Teamwork with volunteers--it is good to have a friend].

PMID- 7817285
TI  - [Cross-professional teamwork--better network for families with infants].

PMID- 7817286
TI  - [Cross-professional teamwork--one must be willing to work cross-professionally.
      Interview by Randi Sandbeck].

PMID- 7817287
TI  - [Maternity clinic--need mothers' experiences].

PMID- 7817288
TI  - [USA--wear and tear].

PMID- 7817289
TI  - [Zanzibar: technique rather than care].

PMID- 7817291
TI  - [Liver transplantations--responsibility].

PMID- 7817290
TI  - [Norway--strike ended with forced arbitration].

PMID- 7817292
TI  - [It is so difficult].

PMID- 7817293
TI  - [Documentation needs practice in writing].

PMID- 7817294
TI  - [District psychiatry: more than mental suffering].

PMID- 7817295
TI  - [Patient information--center supplements the wards].

PMID- 7817296
TI  - [Latvia--the mental straightjacket].

PMID- 7817297
TI  - [Greenland--what is health?].

PMID- 7817298
TI  - [Private hospitals--Mermaid faces the music].

PMID- 7817299
TI  - [Private hospitals--close patient contact adds to job satisfaction].

PMID- 7817300
TI  - [Liver transplantation--Arhus supposed to be the best].

PMID- 7817301
TI  - [Research: the Danes are failing].

PMID- 7817302
TI  - [Research: to be pro-active. Interview by Grethe Kjaergaard].

PMID- 7817303
TI  - [Research: poor standard in spite of adequate knowledge. Interview by Grethe
      Kjaergaard].

PMID- 7817304
TI  - [WHO--health goal for the year 2001].

PMID- 7817305
TI  - [Research: Arhus is good--but not good enough].

PMID- 7817306
TI  - [Research: a decade of strategies].

PMID- 7817307
TI  - [Health care--good enough every time].

PMID- 7817308
TI  - [Ethics--advertising and professional credibility].

PMID- 7817309
TI  - [Dementia--an almost universal family].

PMID- 7817311
TI  - [Nursing practice--so many walk on the wild side].

PMID- 7817312
TI  - [Attempted suicide--paracetamol poisoning].

PMID- 7817310
TI  - [Child nutrition--out of confusion].

PMID- 7817313
TI  - [Drug advertising--4 suicides in 50. Interview by Kirsten Bjornsson].

PMID- 7817314
TI  - [Awakening--a good atmosphere].

PMID- 7817315
TI  - [Psychiatric nursing--supervision in a somatic department].

PMID- 7817316
TI  - [Euthanasia: helping to die is an admission of failure].

PMID- 7817317
TI  - [Nursing theory--the rational and the sensitive].

PMID- 7817318
TI  - [Team work with volunteers--helping works both ways].

PMID- 7817319
TI  - [History--angels of light in blue and white].

PMID- 7817320
TI  - [Nutrition--the art of seduction].

PMID- 7817321
TI  - [Health policy--hospitals in the year 2010].

PMID- 7817322
TI  - Going for all the marbles. Lawsuit reform group hopes to enact sweeping tort
      changes.

PMID- 7817323
TI  - Last-minute strategies. Experts say it's not too late to cut your taxes (but you
      should have been planning all year).

PMID- 7817324
TI  - Meeting of the minds. TMA-led coalition reaches consensus on plan to boost
      primary care education.

PMID- 7817325
TI  - A new yardstick. Outcomes measurement and practice parameters are a growing part
      of medical practice.

PMID- 7817326
TI  - Risky business. Financial incentives in managed care warrant regulation.

PMID- 7817327
TI  - Management of the third stage of labor: a survey of practice among Texas
      obstetricians.
AB  - Available evidence shows that the benefits of routine oxytocic administration in
      the third stage of labor far outweigh the potential risks. In 1990, T.F. Baskett,
      MD, reviewed the routine use of oxytocic drugs by Canadian obstetricians in the
      management of the third stage of labor. With Dr Baskett's permission, we sent a
      similar questionnaire to 1500 obstetricians in Texas: 1000 practiced in urban
      areas and 500 practiced in rural areas of the state. Ninety-four percent of Texas
      obstetricians answering the survey used oxytocics routinely in managing the third
      stage of labor. However, only 14.9% administered the oxytocics before delivery of
      the placenta, in contrast to 92.1% who gave oxytocics after the delivery of the
      placenta. Oxytocin was the chosen oxytocic drug for routine third-stage
      management (95%) as well as for postpartum hemorrhage (73.3%). Of the physicians
      surveyed, 55.9% used 15-methyl prostaglandin F2a (Hemabate) to treat postpartum
      hemorrhage refractory to other drugs within the past year. Of the respondents,
      14.3% had managed acute uterine inversion during the past year. Thus, Texas
      obstetricians use Oxytocin routinely in the management of the third stage of
      labor, but few are converted to active management.

PMID- 7817329
TI  - UT Southwestern researcher wins Nobel Prize.

PMID- 7817328
TI  - Prevalence of HIV seropositivity among inner-city adolescents in 1988 and 1992.
AB  - The purpose of this study was to document the change in prevalence of human
      immunodeficiency virus (HIV) infection among sexually active minority teens at a
      primary and reproductive teen health clinic. Both new and current patients were
      sampled in a seroprevalence study in 1988 and again in 1992. None of the 1200
      adolescents sampled were seropositive for HIV in 1988. Nine of the 1085
      adolescents sampled were seropositive in 1992. Five of these 9 teens reported
      heterosexual contact only as a potential risk factor. Six of these 9 teens were
      not in school. These results suggest that HIV infection is increasing among Texas
      urban teens. Because current education programs do not appear to be preventing
      viral spread, new, focused intervention must be initiated for teenagers. In
      particular, an effective acquired immunodeficiency syndrome prevention program
      for out-of-school youth is needed urgently.

PMID- 7817330
TI  - Giving away our nursing gift.

PMID- 7817331
TI  - [Evaluation of hospital cost of six days of treatment of deep venous thrombosis.
      Comparison of subcutaneous nadroparin and intravenous heparin in 40 patients].
AB  - For curative treatment of deep vein thrombosis, all trials have shown that twice
      a day low molecular weight heparin were at least as efficacious as unfractionated
      heparin on clot reduction or stabilisation. Through the unit cost of low
      molecular weight heparin is higher, the real cost of treatment should take into
      account not only the cost of the drug, but also the cost of materials used and
      lab tests as well as the time necessary. We have therefore prospectively compared
      the operating and overall costs of nadroparin and intravenous heparin treatment
      of deep vein thrombosis in hospitalised patients (21 with unfractionated heparin
      and 19 with nadroparin). The results show that low molecular weight heparin is no
      more expensive than treatment with unfractionated heparin (336 +/- 74.9 F for
      unfractionated heparin and 344.9 +/- 44.05 F for nadroparin). In addition, using
      nadroparin rather than heparin saves approximately one hour per patient per week
      nursing time (42 +/- 7 minutes vs 104.0 +/- 10.7 minutes, p < 0.05). The
      methodology of this study should be repeated with other low molecular weight
      heparin and low molecular weight heparin compare not only to standard i.v.
      heparin, but also to standard SC heparin.

PMID- 7817332
TI  - [Effect of night medical guard on following day vigilance. Influence of hypnotic
      drug on recovery night and on the vigilance during the following day].
AB  - The consequences of sleep deprivation on vigilance and mood were evaluated in six
      healthy medical students the day after being on night duty and the following day,
      after recovering from a full night's sleep. Diurnal vigilance was studied using
      the Multiple Sleep Latency Test (MSLT) and mood was assessed on an anxiety self
      evaluation scale. The study was conducted by means of a double-blind randomized
      trial to measure the effects of benzodiazepine (lormetazepam, 2 mg) compared to a
      placebo administered before the night recovery/full night's sleep. Sleep
      deprivation induced a significant decrease in vigilance the day following the
      night duty. Sleep latencies were shortened during the morning following the night
      of recovery/full night's sleep. The values obtained after administering the
      lormetazepam did not differ significantly from those obtained after administering
      the placebo. There were no considerable differences in the anxiety evaluation
      scores before and after the night of recovery/full night's sleep between the two
      sequences of the trial. This study suggests that a significant lack of sleep (a
      36-hour sleep deficit) modifies diurnal vigilance over two nyctohemeral periods.
      Administration of benzodiazepine with a short half-life after occasional sleep
      deprivation does not change the reorganization of the sleep-waking cycle.

PMID- 7817333
TI  - [Does the placebo effect exist in newborn infants?].
AB  - Although comparison with a placebo is necessary to demonstrate the "true" effect
      of a drug, neonatologists are usually reluctant to use a placebo. The reason
      given is the lack of placebo effect in neonates. We studied heart and respiration
      rates and behaviour in normal neonates during heelstick for diagnosis of
      phenylketonuria. In this open randomized study we compared no treatment with an
      "analgesic" treatment consisting of water and sucrose. There was no difference in
      heart and respiration rates and behaviour between the two groups. These results
      do not demonstrate a "suggested" placebo effect and can in part be explained by
      the model and tools used to measure pain. The results do not support the non-use
      of placebo in drug evaluation trials in children.

PMID- 7817334
TI  - [Follow-up of 151 pregnant women exposed to antidepressant treatment (MAOI
      excluded) during organogenesis].
AB  - The Pharmacovigilance and Poisons Center in Lyon undertook an analysis of their
      data on antidepressant (MAOI excluded) exposure during the first trimester of
      pregnancy. From 1986 to 1991, 151 prospective enquiries were collected of which
      145 exposures occurred during the first trimester of pregnancy. The outcome of
      pregnancy was known for 114 of these cases. Voluntary or medical abortion was
      decided in 24 cases, spontaneous abortion occurred in 11 patients and fetal
      death, unrelated to drug exposure, was noted in one case. Delivery was reported
      in 78 cases including 69 (88.5%) normal infants, with obstetrical complications
      not related to the treatment in 7 of these cases. Neonatal complications were
      noted in 5 (6.4%) cases, including withdrawal symptoms possibly related to the
      treatment in 3 cases. Congenital abnormalities were identified in 4 cases (5.1%)
      with one case of major malformation (membranous ventricular septal defect). Such
      a study is not an exhaustive survey of antidepressant exposure during pregnancy,
      but a collection of inquiries received by our centre. Even though our study's
      ability to detect an overall increase in the risk of malformations is too low and
      limited the extent of our conclusion, our results are in agreement with the
      literature data as no important increased in major birth defect was observed.

PMID- 7817335
TI  - [Pharmacovigilance of antibiotics. Evaluation by the Midi-Pyrenees
      Pharmacovigilance Center between 1989 and 1992].
AB  - The present retrospective study investigates the antibiotic-induced side effects
      in a regional French Pharmacovigilance Center between 1989 and 1992. Five-hundred
      and seventy six side effects were reported, involving 611 drugs and accounting
      for 18% of the total activity of the pharmacovigilance center. Most of the side
      effects involved penicillins and systemic quinolones followed by sulfonamides,
      cephalosporines and glycopeptides. When expressed in number of adverse effects in
      Defined Daily Dose, the maximal frequency of side effects was observed with
      sulfonamides. In contrast, the frequency of penicillin-induced adverse events was
      low. The most frequently reported side effects were cutaneous and/or immunologic
      (54%) and digestive (24%) disturbances. Among serious side effects, 3 toxic
      epidermal necrolysis (2 with cotrimoxazole), 16 pseudomembranous colitis (11 with
      beta-lactam antibiotics, 4 with macrolides and lincomycines and 1 with
      vancomycin), 14 neuropsychiatric reactions (seizures, confusions and
      hallucinations with beta-lactam antibiotics and fluoroquinolones) were notified.
      Five antibiotic-induced side effects led to the death.

PMID- 7817336
TI  - [Progressive muscular dystrophies and drug risks].
AB  - Many therapeutic agents are necessary during the evolution of progressive
      muscular dystrophy to cure intercurrent diseases. Some of them may impair
      muscular structure and induce rhabdomyolysis, toxic or inflammatory myopathy.
      Other treatments may produce metabolic and functional alterations or impair
      cardiac and respiratory functions, yet endanged in progressive muscular
      dystrophy. They must be contra-indicated or used carefully during progressive
      muscular dystrophy.

PMID- 7817337
TI  - [Study of hepatic drug metabolism. For a rationalization of a new molecular
      development].
AB  - Interindividual variability of hepatic metabolism of drugs may be responsible for
      decrease in efficacy, increase in the incidence and severity of adverse effects
      or drug-interactions. This variability may be due to hepatic drug interaction,
      specific physio-pathologic condition or genetic polymorphism. Search for
      variability of hepatic metabolism and the factors determining this variability
      during the pre-clinical and clinical development of new drug contributes to an
      individual optimization of treatment during clinical research and after
      introduction into the market. This strategy results in an improvement of the
      benefit-risk ratio. The various methodological approaches to the study of hepatic
      metabolism during the successive phases of drug development and the integration
      of these studies in the clinical development plan of a new drug are discussed in
      this paper.

PMID- 7817338
TI  - Fluoxetine and norfluoxetine plasma levels after treatment discontinuation in
      man.

PMID- 7817339
TI  - [Hemoptysis under acenocoumarol: role of the arrest of enzymatic inductor
      (carbamazepine)].

PMID- 7817340
TI  - [Precipitation of opioid withdrawal syndrome with nalbuphine in a morphine
      dependent cancer patient].

PMID- 7817341
TI  - [Late perfusion with N-acetylcysteine in a case of paracetamol poisoning seen at
      the stage of fulminant hepatitis].

PMID- 7817342
TI  - Report of six sporadic cases of ALS patients receiving ceftriaxone.

PMID- 7817343
TI  - Persistent low plasma levels of HIV-1 in patients on AZT therapy and its
      implications.

PMID- 7817344
TI  - [Hypereosinophilia and maprotiline. Apropos of a case].

PMID- 7817345
TI  - [Chronic diarrhea secondary to Veinamitol].

PMID- 7817346
TI  - [Vertigo and hypokalemia. Two rare side effects of itraconazole].

PMID- 7817347
TI  - Fluvoxamine and galactorrhea. A case report.

PMID- 7817348
TI  - Rhabdomyolysis after moderate alcohol abuse and physical training during
      amesergide treatment.

PMID- 7817349
TI  - Ranitidine induced polyarthropathy.

PMID- 7817350
TI  - [Fatal hepatitis caused by cyproterone acetate].

PMID- 7817351
TI  - [Reactivation of bullous pemphigoid after influenza vaccination].

PMID- 7817352
TI  - [Crystalluria induced by sulfadiazine in an AIDS patient].

PMID- 7817353
TI  - [Acute kidney failure in a patient treated with cyclosporine A and metronidazole
      following kidney transplantation].

PMID- 7817354
TI  - [Physiological mechanisms of cardiovascular adaptation to orthostatism. Role of
      the sympathetic nervous system and pharmacological implications].
AB  - The main physiological adaptative systems occurring during orthostatism are
      discussed. The nervous mechanisms and especially baroreceptor pathways allow a
      rapid adaptation to the new hemodynamic conditions whereas hormones (mainly
      vasopressin) are involved later. The role of baroreflex and cardiocirculatory
      mechanisms is explained by the description of adaptative mechanisms in giraffe,
      an animal with its brain so far above the ground. The changes in adrenoceptor
      receptivity and the adaptative homeostatic mechanisms of the autonomic nervous
      system during orthostatism in human are discussed. Their characterization might
      allow to propose new pharmacological approaches for the treatment of orthostatic
      hypotension.

PMID- 7817355
TI  - [Duration of action of trandolapril in mild to moderate hypertensive patients
      evaluated by ambulatory measurement of blood pressure].
AB  - The duration of the antihypertensive action of transdolapril, a new angiotensin
      converting enzyme inhibitor, was studied in 23 patients using ambulatory blood
      pressure monitoring (ABPM) over 48 hours. After a 20-day placebo period (D1 to
      D20), mild to moderate hypertensive patients received 2 mg trandolapril once
      daily for 30 days (D21 to D50). The first 24-hour ABPM recording was performed on
      day 14, during the placebo run-in period. Two additional recordings were done
      successively on days 50 and 51 corresponding to a normal dosing day and a
      following day with a simulated missed dose, respectively. The three blood
      pressure recordings (placebo, treatment, missed dose) were compared. The average
      24-hour systolic (SBP) and diastolic (DBP) blood pressure were significantly
      decreased by trandolapril. The mean +/- s.d. decrease between day 14 and day 50
      were - 8.0 +/- 7.2 mmHg for the DBP and -13.3 +/- 7.8 mmHg for the SBP. Blood
      pressure was also consistently decreased during the daytime period (-8.7 +/- 7.9
      mmHg for the DBP and - 15.6 +/- 8.5 mmHg for the SBP), nighttime period (-5.6 +/-
      9.1 mmHg for the DBP and - 8.5 +/- 11.3 mmHg for the SBP) and early morning (-
      12.3 +/- 9.7 mmHg for the DBP and - 15.9 +/- 15.1 mmHg for the SBP). The normal
      circadian pattern of blood pressure was maintained under treatment. The
      antihypertensive effect of trandolapril was sustained beyond 24 hours after the
      last intake: there were no significant difference beetween days 50 and 51 in
      terms of 24-hour, daytime and nighttime average blood pressure.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7817357
TI  - The physiological aspects of fibrinolysis.

PMID- 7817356
TI  - [Efficacy of benazepril after failure of the first antihypertensive treatment].
AB  - The aim of the study was to evaluate efficacy of benazepril prescribed as
      replacement therapy in patients with mild to moderate hypertension, according to
      the pharmacological class of the previous unsuccessful drug. After wash-out of
      the ineffective or badly tolerated medication, 814 patients were randomly and
      blindly assigned to receive either benazepril 10 mg (group 1), benazepril 20 mg
      (group 2) or benazepril 10 mg plus hydrocholorothiazide 12.5 mg (group 3) once
      daily. The mean DBP changes from baseline were highly significant in each group
      (p < 0.001), and greater in groups 2 and 3 versus group 1 (p = 0.003). There was
      a non-significant trend for a greater efficacy of benazepril when the previous
      therapy was a diuretic or a calcium inhibitor. In this study, benazepril appears
      to be efficient as replacement therapy in moderate hypertension, but no link was
      demonstrated between the quality of the result and the nature of the previous
      drug.

PMID- 7817358
TI  - High shearing forces in blood: haemostasis, thrombosis and atherogenesis.

PMID- 7817359
TI  - Production of tissue factor by monocyte progenitor cells.
AB  - Tissue factor (TF) is known to be produced by monocytes from human peripheral
      blood. However the production of this factor by haematopoietic progenitor cells
      is not yet known. We thus studied human monocyte progenitor cells isolated from
      bone marrow of normal and diseased individuals. These cells were non-adherent,
      monocytic and able to phagocytose particles ranging from 0.3-1 microns.
      Unactivated partial thromboplastin time clotting assay demonstrated procoagulant
      activity consistent with TF function, which was blocked by a neutralizing anti-TF
      monoclonal antibody, G12. The production of TF messenger RNA was demonstrated on
      dot blot and northern blot analysis utilizing an oligonucleotide probe.

PMID- 7817360
TI  - Resistance to activated protein C: evaluation of three functional assays.
AB  - Resistance to Activated Protein C (APC) was evaluated using 3 different methods:
      two of them were based on the prolongation of the Activated Partial
      Thromboplastin Time (APTT) using 2 different APTT reagents in the presence of
      APC, whereas the third method was based on the prolongation of prothrombin time
      when APC is added. The three methods were significantly correlated. APTT-based
      assays were sensitive to factor XII deficiency, whereas thromboplastin-based
      assay was sensitive to factor VII deficiency (< 0.5 UI/ml), which surestimates
      the response to APC. In contrast, an increase in factor VIII (F. VIII) level is
      associated with a decreased response to APC, when APTT-based assays are used,
      whereas thromboplastin-based assay is unmodified. During pregnancy, a decreased
      response to APC is observed, which is not only due to the increase in F. VIII,
      since thromboplastin-based assay is also modified. In Protein S (PS) immuno
      depleted plasma, the low response to APC is corrected by addition of free PS: the
      thromboplastin-based assay was the most sensitive one to PS deficiency. However,
      in patients with congenital PS deficiency, there was no correlation between APC
      resistance and free PS level. In patients with lupus anticoagulant, discrepancies
      were observed between the 3 methods, but with a high frequency of low response to
      APC. For the 3 assays, there was a good differentiation and correlation between
      normal and pathological results, the thromboplastin-based assay being perhaps the
      most discriminating. However, 3 unrelated thrombophilic patients showed normal
      results using thromboplastin-based assay, although they were APC-resistant using
      APTT-based assays. For 2 patients, this discrepancy can be explained by high
      levels of F. VIII. For the last patient, an abnormal F. VIII, resistant to APC
      can be suspected.

PMID- 7817361
TI  - Nitrogen microbubbles induce a disappearance of single platelets (aggregation)
      with porcine platelets: a comparative study of the effects of anticoagulants and
      blood collection methods.
AB  - The pathogenesis of decompression illness (DCI) is uncertain. DCI involves all
      parts of the organism where gas bubbles are produced. They have both primary and
      secondary effects and have been classified as an agonist aggregating human
      platelets. In vitro effects of N2 bubbles on porcine platelets were investigated.
      Comparative studies using two different anticoagulants and three different
      sampling methods were performed. A disappearance of single platelets interpreted
      as platelet aggregation was observed in the presence of N2 bubbles in all studied
      groups. Aggregatory responses were more profound with platelets in heparinized
      plasma than in citrated plasma. In citrated plasma the aggregatory responses were
      more profound when blood was obtained from nonanaesthetized (awake) animals than
      from slaugtherhouse animals. Adrenaline (1 microM) had an inhibitory effect on N2
      bubble induced platelet aggregation in vitro. The pig could be useful to
      investigate possible gas bubble effects in vivo.

PMID- 7817363
TI  - Platelet response to vascular surgery--a preliminary study on the effect of
      aspirin and heparin.
AB  - Patients with peripheral arterial disease (PAD) demonstrate high cardiovascular
      mortality, which is further increased after arterial reconstruction. Enhanced
      platelet reactivity has been postulated for these patients. The effect of surgery
      and of periprocedural aspirin and heparin therapy on platelet reactivity was
      assessed with the Stagnation Point Flow Adhesio-Aggregometer (SPAA). The platelet
      adhesivity and aggregability of 44 PAD patients was quantitated perioperatively.
      Aspirin was administered during the entire course, low molecular weight heparin
      (LMWH) preoperatively and as of the fourth postoperative (pOP) day and
      unfractionated heparin (UH) upon surgery and three days thereafter. A group of 15
      aspirin-free general surgical patients receiving LMWH and with no evidence of PAD
      served as controls. Plasma fibrinogen levels and platelet count were determined.
      The heparin-induced platelet activation (HIPA) assay for detection of heparin
      associated thrombocytopenia (HAT) antibodies was also performed. Baseline values
      of SPAA-measured platelet reactivity (p < 0.001) and plasma fibrinogen (p < 0.01)
      were higher for patients as compared to controls and increased markedly after
      surgery. In the PAD group maximum platelet activation and fibrinogen levels
      coincided with a marked drop in platelet count and were concomitant to
      administration of unfractionated heparin. Thereby, a drop in platelet count of >
      30% was observed in 25 patients (57%). The HIPA test verified HAT antibodies in 3
      (12%) of these patients, two of which suffered postoperative thrombosis. In the
      control group significant pOP increases were noted only for plasma fibrinogen.
      Changes in platelet count and reactivity were minimal and nonsignificant. No
      thrombosis occurred and no HAT antibodies were detected.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7817362
TI  - Endothelin-1 increased immunoreactive von Willebrand factor in endothelial cells
      and induced micro thrombosis in rats.
AB  - This study was performed (i) to investigate the interaction between ET-1 and
      endothelial cells and (ii) to study the role of ET-1 in in vivo thrombosis. Fura
      2AM loaded human umbilical endothelial cell cultures were incubated with 0, 25,
      50 and 100 pmol of ET-1 for 24 hours (n = 6) at 37 degrees C. Fura-2 released in
      the media was measured by spectroflurophotometer at wavelength of 350 nm
      excitation and 500 nm emission. We found significant (p < 0.01) and dose
      dependent decrease in Fura-2 release by the cells indicating increased
      intracellular calcium in HUVEC. Increased calcium by ET-1 was also confirmed at
      single cell level by fluorescence digital image analysis using Fura-2AM. 5 ml
      solution of ET-1 (100 pmol/ml) was injected within the venous lumen of umbilical
      cords (of normal pregnancy) clumped at both ends and incubated at a temperature
      37 degrees C for 3 hours (n = 7). We found intensely stained immunoreactive von
      Willebrand factor (vWF) on the endothelial cells of ET treated umbilical cords
      when compared with sham control (Umbilical cords incubated with phosphate buffer
      saline; n = 7). Intravenous ET-1 infusions at a rate of 1 nmol/kg/hour for 2
      hours (cases, n = 7) and 5% dextrose infusions (sham control, n = 7) were
      performed in rats. Aorta, kidney and liver tissues were obtained to perform
      immunostaining with polyclonal antibody to vWF and fibrinogen. ET-1 treated rat
      tissues showed intense staining for vWF and fibrinogen intravascularly at hte
      same site.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7817364
TI  - Diacylglycerol formation induced by human plasmin in cultured endothelial cells.
AB  - Treatment of cultured bovine carotid artery endothelial cells with 10(-7) M
      plasmin increased the cellular diacylglycerol which was determined by the
      formation of [3H]palmitate-labeled diacylglycerol and diacylglycerol mass. Upon
      the stimulation with plasmin, a gradual increase in diacylglycerol formation was
      observed within 20 min then slightly declined. The maximal effect during the 1-h
      time course study was 45 and 55% increases in [3H]palmitate-labeled
      diacylglycerol and diacylglycerol mass, respectively, at 20 min after plasmin
      treatment. Formation of phosphatidylethanol was also studied in [3H]palmitate
      prelabeled cells in the presence of ethanol. Treatment with plasmin for 20 min
      induced a significant 45% increase in phosphatidylethanol formation. The present
      results indicate that the plasmin-induced diacylglycerol formation in endothelial
      cells was at least in part mediated through the phospholipase D activation.

PMID- 7817365
TI  - Fibrinolysis and serotonin under cyclosporine A treatment in renal transplant
      recipients.
AB  - Cyclosporine A (CyA), a potent immunosuppressive drug, has been used in renal
      transplant recipients with increasing frequency since 1982. Despite its efficacy,
      CyA therapy has been associated with an increased incidence of thromboembolic
      complications. This has been attributed to increased thromboxane production,
      reduced prostacyclin synthesis and increased platelet aggregability. The
      coagulation system is also altered in CyA-treated patients and some of these
      changes would favor thrombosis. Increased fibrinogen and FVII:C levels have also
      been associated with an enhanced risk of thrombosis. In contrast, CyA therapy was
      reported to increase the levels of antithrombin III and protein C, two proteins
      known to protect against venous thromboembolism. However, the possible effect of
      CyA on the fibrinolytic system has not been thoroughly investigated and rather
      confusing data have been reported concerning both enhancement and suppression of
      fibrinolysis. Serotonin (5-hydroxytryptamine, 5-HT) may play a role in hemostasis
      and platelet/vessel wall interactions. It may facilitate platelet thrombus
      formation by potentiating the aggregatory response to other agents such as ADP,
      collagen or epinephrine and by causing vasoconstriction. Taking all these data
      into consideration we have measured some fibrinolytic parameters, whole blood and
      plasma serotonin concentration in cyclosporine A- and non-cyclosporine A-treated
      kidney transplant recipients.

PMID- 7817366
TI  - [Lower dosage--optimal effect in companion animal practice].

PMID- 7817367
TI  - [Scrapie and BSE, the status ib The Netherlands].

PMID- 7817368
TI  - [Feed medication interesting in spite of limitations].

PMID- 7817369
TI  - [Pioneers from earlier times (7). Carlo Ruini].

PMID- 7817370
TI  - [Uterus relaxants in the cow].

PMID- 7817371
TI  - [Presenting the results of medical and workplace studies. Veterinarians should
      take care of themselves].

PMID- 7817372
TI  - [Veterinary dentistry (7). Development, anatomy and function of teeth in the
      cat].
AB  - This article in the series about the dentistry of companion animals deals with
      feline dentistry. Odontogenesis, eruption times, and the appearance of teeth are
      described briefly. Certain cat-specific characteristics of the anatomical
      features of the teeth and periodontium are described. The shape and position of
      tooth elements, terminology, and modern techniques for determining the position
      of tooth elements are dealt with in depth. Attention is paid to the relationship
      between the upper and lower jaws and occlusion in cats with an abnormal bite.

PMID- 7817373
TI  - [Incarcerated umbilical hernia with enterocutaneous fistula in a calf].
AB  - A 3-week-old heifer was referred to the clinic for a suspected fistula of the
      urachus. Clinical examination revealed the calf to be in moderate condition with
      an umbilical hernia and an enterocutaneous fistula. Although in calves the
      abomasum is usually involved in the fistula, it became clear at surgery that this
      calf had a fistula of the small intestine. The treatment and surgical technique
      used are discussed.

PMID- 7817374
TI  - Biochemical characterization of bovine MHC DQ allelic variants by one-dimensional
      isoelectric focusing.
AB  - Previous studies on expressed bovine MHC class II polymorphism using one
      dimensional isoelectric focusing (1D-IEF) allowed the identification of at least
      12 allelic variants of the DRB3 gene. So far, only limited data have been
      available on the expression of other class II genes. The present study involved
      biochemical analysis of bovine MHC class II molecules using a set of monoclonal
      antibodies presupposed to be bovine DR and DQ reactive. After essential
      modification of the standard electrophoresis conditions used for 1D-IEF typing of
      bovine DR products, biochemical polymorphism was observed for non-DR molecules,
      revealing polymorphic sets of basic and acidic focusing bands. Because of the
      extensive DNA polymorphism described for bovine DQA and DQB genes, and the
      apparent similarity with the focusing pattern of human DQ products, these
      molecules were considered to be the bovine DQ homologues. The definition of the
      DQ-associated banding patterns was made possible by using two half-sib sire
      families. Four different DQA-like patterns and nine DQB-like patterns were
      detected. Segregation of the DQ types was supported by serological class I and
      class II typing. These results show that it is now possible to discriminate
      between expressed bovine DR and DQ polymorphism.

PMID- 7817375
TI  - Analysis of antibody markers, DRB1, DRB5, DQA1 and DQB1 genes and modeling of DR2
      molecules in DR2-positive patients with insulin-dependent diabetes mellitus.
AB  - HLA-DR2 is negatively associated with insulin-dependent diabetes mellitus (IDDM).
      The aim of the present study was to analyze DR2-positive patients among 425
      consecutively diagnosed unrelated Swedish children with IDDM and in 367 matched
      controls. HLA-DRB, -DQA and -DQB were determined by Taq I restriction fragment
      length polymorphism analysis. Amplification by polymerase chain reaction (PCR)
      and hybridization with sequence-specific oligonucleotide probes was done for
      DQA1, DQB1 and DRB1 and DRB5. DR2 was positive in 11/425 patients (3%) and
      101/367 (28%) controls (OR 0.07, p < 0.0001). Of the 11 DR2-positive patients,
      PCR was done in 10, of whom 8 were positive for DRB1*1601-DRB5*0201 compared to
      4/96 (4%) controls (OR 92.0: p < 0.001) while the remaining 2 were positive for
      DRB1*1501-DRB5*0101 compared to 92/96 (96%, OR 0.01; p < 0.001). In 2 patients, a
      recombination between the haplotypes DQB1*0502-DQA1*0102 (DQ5)-DRB1*1601
      DRB5*0201 (DR16 Dw21) and DQB1*0301-DQA1*0501 (DQ7)-DRB1*1602-DRB5*0202 (DR16
      Dw22) was observed resulting in the DQB1*0301-DQA1*0501 (DQ7) DRB1*1601-DRB5*0201
      (DR16 Dw22) haplotypes. The second haplotype was DR3 DQ2 in 6/11 and DR4 DQ8 in
      2/11 DR2-positive patients. In all 3 DQB1*0602-DQA1*0102-DR15-positive patients
      the second haplotype was DR4-positive. In order to test whether physicochemical
      properties of the DR2 molecules were associated with IDDM, we constructed three
      dimensional models of the peptide binding and T-cell recognition sites (alpha 1
      and beta 1 domains) of five subtypes of DR2-DRB1, based on the published DR1
      crystal structure. No correlations were observed for DR molecule physicochemical
      properties and diabetes susceptibility. Islet cell antibodies, insulin
      autoantibodies and GAD65 antibodies, were measured in DR2-positive patients (n =
      11) and controls (n = 101). Despite the presence of the DR2 haplotype the
      antibody markers were significantly elevated in the patients compared to the
      controls (GAD65 3/10 patients and 2/101 controls; ICA 7/11 patients and 1/101
      controls and IAA 3/11 patients and 0/101 controls). In conclusion, of the five
      subtypes of DR2, only one, the DRB1*1501, DRB5*0101, DQB1*0602-DQA1*0102
      haplotype, was negatively associated with IDDM. DQ may therefore confer more
      protection from the disease than DR.

PMID- 7817376
TI  - Identification of a novel DQB1 allele (*0609) segregating in an Ashkenazi Jewish
      family: implications for DQB1 typing systems.

PMID- 7817377
TI  - Molecular analysis of MHC class II alleles and haplotypes (DRB1, DQA1 and DQB1)
      in the Bari Amerindians.

PMID- 7817378
TI  - HLA and susceptibility to insulin-dependent diabetes mellitus on the island of
      Corsica.

PMID- 7817379
TI  - A novel HLA-DPB1 allele, DPB1*3601 (DPB1*KT).

PMID- 7817380
TI  - HLA class I self peptides isolated from a T-cell leukemia reveal the allele
      specific motif of HLA-B38.
AB  - Naturally-processed self peptides bound to HLA class I molecules of a T-cell
      leukemia (HLA-A1, A31, B38, B58) were isolated for sequence analysis. Acid-eluted
      peptides were subjected to reversed-phase HPLC separation and single-fraction
      sequencing was performed by Edman degradation. The peptides were found to be
      mostly nonamers and could be grouped into three distinct structural motifs. One
      of the peptide groups consistently displayed histidine at position 2 and a bulky
      hydrophobic residue at the C-terminus (XHXPXXXXY/F). The only HLA class I
      structure expressed by this T-cell leukemia which is consistent with the binding
      of peptides carrying this sequence motif is HLA-B38. A peptide binding assay
      confirmed this assignment. HLA-B38 is present in 10-12% of the Jewish population
      and is associated with several autoimmune disorders. The HLA-B38 motif may be an
      important tool for identifying potential T-cell epitopes involved in these
      diseases and for designing peptide vaccines.

PMID- 7817381
TI  - UN1, a murine monoclonal antibody recognizing a novel human thymic antigen.
AB  - A murine monoclonal antibody (mAb) UN1 was produced on the basis of selective
      reactivity with human thymocytes. Characterization of UN1 by immunofluorescence
      gave a high intensity of labeling with the majority of human thymocytes.
      Expression was preferentially associated with immature thymocytes (CD3dim)
      compared to mature cells, whereas only a subpopulation of peripheral blood
      lymphocytes was weakly stained. No specific binding to monocytes or granulocytes
      was detected. The T-cell lines HPB-ALL, H9 and MOLT-4 were all positively bound
      by UN1. Immunohistological staining of thymic tissues showed that mAb UN1
      detected cells in both the cortex and medulla of fetal thymus, whereas the
      reaction in thymus samples from young children was mainly with medullar cells. By
      western blotting analysis, the antigen recognized by mAb UN1 corresponds to a
      membrane polypeptide with a molecular weight of approximately 120 kDa present on
      thymocytes and HPB-ALL cells. The mAb UN1 was submitted to the 5th International
      Workshop and Conference on Human Leukocyte Differentiation Antigens, Boston,
      1993. UN1 did not cluster in any of the old or new clusters of differentiation
      discussed at the conference, indicating its unique reactivity. Together with the
      data presented in this paper, this suggests that the UN1 antibody defines a
      previously undescribed molecule present on the cell surface of thymocytes and a
      minority of peripheral blood lymphocytes.

PMID- 7817382
TI  - Role of the mixed lymphocyte culture (MLC) reaction in marrow donor selection:
      matching for transplants from related haploidentical donors.
AB  - The utility of the MLC assay as a test of HLA-D region matching and predictor of
      acute graft-versus-host disease (GvHD) was evaluated in 157 patients receiving
      marrow grafts from HLA-A, B identical related haploidentical donors. All donors
      and recipients were tested by HLA-DR serology, by Dw phenotyping with homozygous
      typing cells (HTC) and by standard MLC. Ninety-nine of the donor-recipient pairs
      were mismatched for a serologically defined HLA-DR antigen while 109 pairs were
      mismatched for the HLA-DR region by HTC typing. Donor antirecipient relative
      responses (RR) in MLC, corresponding to the GvHD vector in marrow
      transplantation, ranged from -4% to 100%, with a median of 25%. A comparison of
      reactivity in MLC with presence or absence of matching by Dw phenotyping,
      however, showed a significant overlap in the distribution of RRs from HLA-Dw
      matched versus Dw mismatched pairs, suggesting that the MLC was not a reliable
      predictor of HLA-Dw matching. Using an optimally-defined cutoff of 3% RR, the MLC
      was correlated with risk of developing clinically significant grades II-IV acute
      GvHD (p = 0.03) but not with risk of developing severe grades III-IV GvHD (p =
      0.18). In contrast, matching by Dw phenotype was a significant predictor of GvHD,
      with Dw-compatible transplant recipients less likely to develop either grades II
      IV (p = 0.004) or III-IV (p = 0.036) GvHD than Dw-incompatible transplant
      recipients. Overall, these results underscore the difficulty in using the MLC to
      measure HLA-D region compatibility and predict the risk of severe graft-versus
      host disease among patients receiving related haploidentical marrow grafts. HLA-D
      (HTC) typing results correlate primarily with DRB compatibility, and with the
      advent of DRB1 allele matching by sequence-specific oligonucleotide probes (SSOP)
      or by direct sequencing, the precision in donor matching achievable with these
      methods is far greater than with either HLA-D typing or direct MLC testing.

PMID- 7817383
TI  - Molecular diversity of the HLA-C locus in unrelated marrow transplantation.
AB  - The diversity of HLA-C exon-2 alleles in 56 HLA-A, B, DRB and DQB1-matched
      patient-unrelated marrow donor pairs was examined by non-cloning polymerase chain
      reaction-based sequencing of genomic DNA. This method allows simultaneous
      analysis of both alleles in heterozygous samples. All Cw5-positive individuals
      encoded a sequence which differed from the published Cw*0501 sequence at position
      61. Among 82 samples assigned a single antigen by serologic testing, 64 (78%)
      were heterozygous for two distinct alleles when tested by sequencing. Cw*1202,
      1601 and 15 were identified in samples for which no phenotype could be assigned
      (C "blank"). Finally, 7 of the 56 HLA-A, B, DRB, DQB1-matched pairs (12.5%) were
      mismatched for one or both HLA-C alleles. We conclude that sequence-based methods
      constitute the optimal strategies for typing HLA-C alleles in the unrelated
      marrow transplant population.

PMID- 7817384
TI  - Decreased gastric secretory functions in diabetic patients with autonomic
      neuropathy.
AB  - A total of 37 subjects consisted of 10 healthy subjects (Group III), 15 diabetic
      patients without autonomic neuropathy (Group II), and 12 diabetic patients with
      autonomic neuropathy including gastroparesis in 6 cases (Group I). All three
      groups were comparable in age. In order to clarify the gastric function in
      diabetic patients with autonomic neuropathy, secretion of serum gastrin, gastric
      secretory function, endoscopic Congo red test of fundic glands, and coefficiency
      of variance of electrocardiographic beat-to-beat intervals (C.V. R-R) were
      examined. In Group I, 5 patients had hypergastrinemia, but its elevation was
      inhibited when an acid solution was injected into the stomach. Gastric secretion
      and C.V. R-R were markedly lower in Group I, compared with Groups II and III. In
      Group I, the area of fundic glands (parietal cells) was reduced considerably. The
      C.V. R-R was significantly correlated with fasting serum gastrin concentration
      and with maximal acid output. From these results, in diabetic patients with
      autonomic neuropathy (vagal neuropathy), gastric acid secretion in response to
      tetragastrin stimulation was lowered with a reduction in area of fundic gland
      distribution. Hypergastrinemia may reflect a negative feedback mechanism
      responding to decreased acidity of gastric content in the antrum.

PMID- 7817385
TI  - Lipoprotein(a) as an independent risk factor for diabetic retinopathy in male
      patients in non-insulin-dependent diabetes mellitus.
AB  - Relationship of the lipoprotein(a) [Lp(a)] concentration as a risk factor
      independent of other factors with the severity of diabetic retinopathy were
      evaluated by multiple regression analysis. The subjects were 158 patients with
      non-insulin-dependent diabetes mellitus (NIDDM). Multiple regression analysis was
      carried with the severity of diabetic retinopathy as the dependent variable and
      13 independent variables, namely the Lp(a) concentration, sex, age, body mass
      index, duration of diabetes, ischemic heart disease, fasting plasma glucose,
      glycosylated hemoglobin A1c, total cholesterol, triglyceride, high-density
      lipoprotein cholesterol, anti-diabetic treatments, and diabetic nephropathy. The
      analysis was performed separately in all subjects, males only, and females only.
      The standard partial regression coefficient of Lp(a) was significant (0.293, p <
      0.01), and the multiple correlation coefficient was 0.611 in the males. However,
      the standard partial correlation coefficient of Lp(a) was not significant in all
      patients and in females only. The rank of contribution of Lp(a) to retinopathy
      was the third in males, following triglyceride and nephropathy and followed by
      anti-diabetic treatments. These results suggest that Lp(a) might be an
      independent risk factor for diabetic retinopathy in male patients with NIDDM.

PMID- 7817386
TI  - Syalil-SSEA1(SLX) levels in supernatant of cultured human lung carcinoma cell
      lines.
AB  - SLX levels in the culture supernatant of the following 50 cell lines were
      measured by RIA: pulmonary carcinoma cell lines derived from 46 patients, cell
      lines of other human cancers derived from 4 patients, and 2 passaged human
      fibroblast cells as control. Of the 46 pulmonary carcinoma cell lines, 17 (37%)
      were SLX positive. When the SLX-positive rate was analyzed in relation to the
      histological type of pulmonary carcinoma, the positive rate was 71% (10/14) for
      adenocarcinoma, 27% (3/11) for squamous cell carcinoma, 33% (2/6) for large cell
      carcinoma, 0% (0/11) for small cell carcinoma and 50% (2/4) for adenosquamous
      cell carcinoma. Analysis of the relationship between tumor cell proliferation and
      SLX level in 20 patients revealed that the SLX level in the supernatant of SLX
      producing cell lines becomes higher in proportion to the increase in the number
      of these cells. The SLX-positive rate did not differ significantly among
      different stages of pulmonary carcinoma at the time of tissue collection. There
      was no significant correlation between SLX production and prognosis. SLX
      production by each cell line was not correlated with the doubling time of the
      same cell line in vitro or in vivo (in nude mice). SLX production also showed no
      correlation with the duration of tumor cell passage.

PMID- 7817387
TI  - Effects of interleukin-1 beta on blood pressure, thermoregulation, and the
      release of vasopressin, ACTH and atrial natriuretic hormone.
AB  - To assess how interleukins (IL) affect the release of vasopressin (AVP), atrial
      natriuretic hormone (ANH), and ACTH and the regulation of blood pressure (BP),
      heart rate (HR) and rectal temperature (RT), the 3 doses of 1.73 (low dose, LD),
      8.63 (medium dose, MD), and 43.16 pmol/100 gBW (high dose, HD) of human
      recombinant IL-1 beta were intravenously (iv) administered in conscious rats, and
      plasma AVP, ANH, and ACTH, BP, HR and RT were determined simultaneously. In the
      control group (CON), the drug was omitted. Circulatory IL-1 beta levels were
      determined in each dose, and indomethacin (1 mg/rat, IM) was administered iv in
      the HD and CON groups. Plasma IL-1 beta increased transiently following IL-1 beta
      administration in each group. Plasma AVP, ANH, and ACTH increased in the LD, MD,
      and HD groups, respectively. Mean arterial BP (MABP) and RT increased in the LD
      group, but HR did not change. In the MD and HD groups, MABP decreased at 30 min
      followed by its increase at 120 min, but RT in both groups decreased. In the CON
      group, these parameters did not change. IM attenuated plasma AVP and ACTH
      responses to HD and also inhibited decreases in MABP and RT. These results
      suggest that IL-1 beta affects the release of AVP and ACTH, blood pressure and
      thermogenesis via prostaglandins (PGs), but ANH release related to IL-1 beta may
      not be mediated by PGs.

PMID- 7817388
TI  - Three types of "mid-band" lipoproteins in non-insulin-dependent diabetes
      mellitus: relation to metabolic abnormalities and vascular complications.
AB  - A number of fine bands which occur in positions between the beta- and pre-beta
      lipoproteins in polyacrylamide gell electrophresis are called mid-bands (MB). In
      this study, the relationship between the occurrence of these MB and metabolic
      abnormalities or vascular complications was evaluated in 181 patients with non
      insulin-dependent diabetes mellitus (NIDDM). The incidence of MB in diabetic
      patients was significantly higher than that in 149 healthy control subjects (35
      vs. 20%, p < 0.01). Analysis according to the type of MB revealed that the
      incidence of the central type in diabetic patients was significantly higher than
      that in healthy control subject (11 vs. 5%, p < 0.05). When the values of HbAlc
      were elevated, the incidence of MB and its central type slightly increased. The
      occurrence of the lower type of MB showed no relationship with the levels of
      HbAlc. The incidence of MB and its central type were significantly higher in
      patients with type IIb hyperlipidemia (86 and 41%, respectively) and with type IV
      hyperlipidemia (63 and 25%) than in those with normolipidemia (21 and 5%) (p <
      0.01 of all). The incidence of the lower type of MB was significantly higher in
      patients with type IIa hyperlipidemia (25%) and with type IIb hyperlipidemia
      (36%) than in those with normolipidemia (11%) (p < 0.05, p < 0.01, respectively).
      There was no significant difference in the occurrences of MB and of the central
      and lower types of MB between the normolipidemic patients and healthy control
      subjects. The incidence of MB and its central type were significantly higher in
      patients with nephropathy (54 and 23%, respectively) than in those without
      nephropathy (32 and 9%) (p < 0.05 of all). There was no significant difference in
      the incidence of lower type of MB between patients with and without nephropathy.
      These results indicate that the incidence of central type of MB may be high in
      NIDDM, and that the occurrence of central type may be associated with abnormal
      metabolism of glucose or lipid and with diabetic nephropathy.

PMID- 7817389
TI  - Electrophysiological studies of the biceps brachii activities in supination and
      flexion of the elbow joint.
AB  - Activities of the biceps brachii (long head: BiL, short head: BiS) on the elbow
      joint were studied using an electrical neuromuscular stimulation (ENS) and an
      electromyography (EMG). In ENS study, ENS to BiL or BiS was performed in seven
      volunteers. Before ENS, the volunteer relaxed the upper extremity on a table with
      the elbow extended and the forearm pronated. Then ENS-induced movements of the
      upper extremity were examined. Movements of elbow flexion and forearm supination
      were induced simultaneously by ENS to BiS in all volunteer and by ENS to BiL in
      six volunteers. ENS to BiL of one volunteer resulted in only elbow flexion. In
      EMG study, averaged EMGs of BiL and BiS during a to-and-fro motion from prone to
      supine of the forearm with holding a load were analyzed in eight volunteers. The
      volunteer acted the movements with keeping the elbow joint in different angles.
      Although an increase and a decrease of EMG activities in BiL and BiS were
      observed accompanied by the degree of forearm supination, patterns of changes in
      quantities of EMG activities to changing elbow angles varied from individual to
      individual. These findings seem to indicate that each human subject has an
      individual use of the biceps brachii for supination movements, while the action
      of the muscle on the elbow joint is similar among the subjects.

PMID- 7817390
TI  - Functional electrical stimulation (FES) to the biceps brachii for controlling
      forearm supination in the paralyzed upper extremity.
AB  - Control of forearm supination using the functional electrical stimulation (FES)
      to the biceps brachii was studied in a C4 quadriplegic patient. As a result of
      FES to the biceps brachii, and the other elbow flexors and extensors, supination
      was induced in maintenance of the elbow in the maximum flexion and extension,
      respectively. Although a range of the movements was still small and limited,
      these findings indicated a possibility of FES to the biceps brachii for
      controlling supination in paralyzed upper extremities.

PMID- 7817391
TI  - New technology for continuous intravenous infusion via the central and portal
      veins in the rat.
AB  - Total parenteral nutrition via the central vein is a technique used extensively
      in basic and clinical research. Recent research has also focused on the
      administration of various drugs and nutrients via the portal vein. To date,
      however, no technique which would permit prolonged continuous infusion
      simultaneously through both the central vein and the portal vein in the rat has
      been reported. The development of such a technique would open up new
      possibilities for utilizing the advantages of each of these two routes and
      contribute to progress in metabolic and nutritional research. To establish such a
      technique, the authors implemented several unique improvements such as the
      application of clamps to minimize bleeding during catheter insertion and an
      increase in the number of sutures to prevent catheter dislodgment. With these
      improvements, it was possible to continuously administer specified doses of
      infusion solution in both veins for 6 days in 156 of 158 rats (99%) in the main
      experiment. We herein describe the techniques used and some of the results
      obtained with this experimental system.

PMID- 7817392
TI  - Invasion of the cabbage patch (should biochemists learn the Krebs cycle or the
      cell cycle?)

PMID- 7817393
TI  - On allosteric mechanisms and acetylcholine receptors.

PMID- 7817394
TI  - A 'membrane attached' alpha-helix: a conserved structural motif in bacterial
      reaction centres, photosystem I and chloroplast NADH-plastoquinone
      oxidoreductase.

PMID- 7817395
TI  - Amino acid sequence motif of group I intron endonucleases is conserved in open
      reading frames of group II introns.

PMID- 7817396
TI  - The POT family of transport proteins.

PMID- 7817397
TI  - Titin and nebulin: protein rulers in muscle?
AB  - Titin and nebulin are giant muscle proteins, both of which are approximately 1
      micron long and are composed of many repeating domains. Titin domains resemble
      type III fibronectin and C-2 immunoglobulins. Both proteins are likely to be
      involved in specifying and stabilizing the highly ordered structure of muscle,
      probably by acting as 'protein rulers' to regulate the assembly of myosin and
      actin filaments precisely.

PMID- 7817398
TI  - Translational control of GCN4: an in vivo barometer of initiation-factor
      activity.
AB  - Phosphorylation of translation initiation factor-2 (eIF-2) is an adaptive
      mechanism for downregulating protein synthesis under conditions of starvation and
      stress. The yeast Saccharomyces has evolved a sophisticated means of increasing
      translation of GCN4 mRNA when eIF-2 is phosphorylated, allowing the induction of
      an important stress-response protein when expression of most other genes is
      decreasing. Because translation of GCN4 mRNA is so tightly coupled to eIF-2
      activity, genetic analysis of this system has provided unexpected insights into
      the regulation of eIF-2 and its guanine nucleotide exchange factor, eIF-2B.

PMID- 7817399
TI  - The leucine-rich repeat: a versatile binding motif.
AB  - Leucine-rich repeats are short sequence motifs present in a number of proteins
      with diverse functions and cellular locations. All proteins containing these
      repeats are thought to be involved in protein-protein interactions. The crystal
      structure of ribonuclease inhibitor protein has revealed that leucine-rich
      repeats correspond to beta-alpha structural units. These units are arranged so
      that they form a parallel beta-sheet with one surface exposed to solvent, so that
      the protein acquires an unusual, nonglobular shape. These two features may be
      responsible for the protein-binding functions of proteins containing leucine-rich
      repeats.

PMID- 7817400
TI  - Methods and reagents. Better competent cells and DNA polymerase contaminants.
AB  - Methods and reagents is a unique monthly column that highlights current
      discussions in the newsgroup bionet.molbio.methods-reagents, available on the
      Internet. This month's column discusses a new method for harvesting Escherichia
      coli cells for transformation, and contaminants found in DNA polymerase stocks
      used for the polymerase chain reaction. For details on how to partake in the
      newsgroup, see the accompanying box.

PMID- 7817401
TI  - DNA workbench.

PMID- 7817402
TI  - Development of the primer-extension approach: a key role in DNA sequencing.

PMID- 7817404
TI  - [Treatment of psoriasis--medical or surgical].

PMID- 7817403
TI  - Columnar organization in the midbrain periaqueductal gray: modules for emotional
      expression?
AB  - Independent discoveries in several laboratories suggest that the midbrain
      periaqueductal gray (PAG), the cell-dense region surrounding the midbrain
      aqueduct, contains a previously unsuspected degree of anatomical and functional
      organization. This organization takes the form of longitudinal columns of
      afferent inputs, output neurons and intrinsic interneurons. Recent evidence
      suggests: that the important functions that are classically associated with the
      PAG--defensive reactions, analgesia and autonomic regulation--are integrated by
      overlapping longitudinal columns of neurons; and that different classes of
      threatening or nociceptive stimuli trigger distinct co-ordinated patterns of
      skeletal, autonomic and antinociceptive adjustments by selectively targeting
      specific PAG columnar circuits. These findings call for a fundamental revision in
      our concept of the organization of the PAG, and a recognition of the special
      roles played by different longitudinal PAG columns in co-ordinating distinct
      strategies for coping with different types of stress, threat and pain.

PMID- 7817405
TI  - [Dermatome-shaving of psoriasis. 7 years of experience].
AB  - Data from the records of 112 patients who were treated with dermatome shaving for
      psoriasis vulgaris were analysed. One hundred and eight patients with 202 areas
      treated were included in the study. Complications occurred in nine patients.
      Thirty-seven patients and 104 areas did not recur during mean follow-up periods
      of respectively 1.4 years and 1.9 years. In all 108 patients the median
      recurrence free period was eight months (range: 0-5.6 years). The median
      recurrence free period for the 202 areas was 13 months (range: 0-8.2 years).
      Reshaving of partial recurrences in 46 patients led to 40% that did not recur.

PMID- 7817406
TI  - [Right of self-determination and the duty to treat--the conflict between the
      patients's right to self-determination and the physician's duty to treat in
      relation to living wills].
AB  - The principle of autonomy requires competency. A competent patient is a patient
      who is capable of exercising his or her right to self-determination. However, in
      practical clinical work there is a continuum between competency and incompetency,
      and it is the doctor who has to decide whether the right to autonomy can be
      meaningfully upheld. When a patient rejects curative treatment, a conflict arises
      between the patient's right to autonomy and the doctor's duty to treat. While
      emphasizing the principle of autonomy is a guideline, the presence or absence of
      a living will is almost misguided. One may fear that the question of whether cure
      or relief is possible may altogether be neglected when a living will is in
      existence. The interpretation of when a living will should be used is dependent
      on the health staff's evaluation. There are widely divergent opinions of when a
      person is unavoidably dying or permanently incapable of taking care of themselves
      physically and mentally. If a treatment does not have a view to a cure, an
      improvement or a relief of symptoms it should in all circumstances be
      discontinued, independently of whether or not a living will is in existence.

PMID- 7817407
TI  - [The postmenopausal ovary--should it be preserved?].
AB  - Oophorectomia per occasionem is often performed in connection with hysterectomy
      in peri- and postmenopausal women as prophylaxis against ovarian cancer.
      Reviewing published articles has shed little light on whether the postmenopausal
      ovaries have an endocrine function, and whether such a function may have
      physiological importance. Population studies of healthy women, comparisons of
      oophorectomized and non-oophorectomized postmenopausal women and measurements of
      ovarian venous gradients have shown that the postmenopausal ovaries contribute
      substantially to the production of androgens, and produce about half the body's
      circulating testosterone. In a number of women there is a continued significant
      oestrogen production in the ovaries during the first five to ten years following
      menopause. After this period the ovarian contribution to the total oestrogen
      production is very small. To what extent the continued androgen production could
      have physiological importance cannot be decided by reviewing the literature.
      Androgens seem to have importance for sexual function, but could possibly also
      have negative effects in the form of an increased risk of cardiovascular disease.
      We lack both epidemiological investigations and in-vitro perfusion studies of
      human ovaries in order to illuminate the physiological function of the
      postmenopausal ovary. In deciding on oophorectomia per occasionem in the
      postmenopausal woman the possible advantages of continued ovarian hormonal
      production must be weighed against the risk of later development of ovarian
      cancer, which is 2%, identical to that of the risk in the background population.

PMID- 7817408
TI  - [Ambulatory ST-segment monitoring after acute myocardial infarction].
AB  - Over the last decade the concept of silent myocardial ischaemia has received
      considerable attention. Without doubt, the increased use of ambulatory ST-segment
      monitoring is the most important reason for the growing interest in this field.
      The prevalence of ambulatory ischaemia after myocardial infarction seems to be
      lower than in other subgroups with coronary artery disease. In postinfarction
      patients, however, a greater proportion of ischaemic episodes are silent. At
      present there is substantial evidence that ambulatory ischaemia provides
      prognostic information in different subsets of patients with previous myocardial
      infarction, but there is considerable disagreement about how this is expressed in
      terms of cardiac events. Patient selection, small patient numbers, and different
      timing of ambulatory monitoring are proposed as important reasons for the
      inconsistent findings. The precise role of postinfarction ambulatory ST-segment
      monitoring in clinical practice has yet to be established.

PMID- 7817409
TI  - [Milker's hand].
AB  - The predominant skin problems in cattle-breeders are toxic and allergic eczemas,
      with cleansers, water, rubber, disinfectants and fodder being the most frequent
      provoking factors. The Danish register of occupational diseases yields
      information based on notifications during the years 1984-1992. Detailed data
      especially concerning dairy farms are not obtainable, but during the whole period
      101 hand-skin diseases in farmers and farming assistants were notified, 12-23
      annually in recent years. This number is not alarming, but there is general
      agreement that underreporting is significant. The main elements of prevention are
      1) reduction of harmful actions and 2) optimization of skin resistance. Among the
      steps that ought to be taken immediately are reduction of contact with cleansing
      and disinfective agents through change of working methods and behaviour.
      Alteration of tools, for instance substitution of rubber with less sensibilizing
      materials, is desirable.

PMID- 7817410
TI  - [4 years of experiences with Karbase. A tool for quality development in vascular
      surgery].
AB  - Karbase, a Danish register for vascular surgery is presented with data from four
      years experience. The register consists of 65 variables centered on risk factors,
      the perioperative course as well as follow-up information. During the four-year
      period 1989-1992 a total of 4902 admissions were registered in 3810 patients.
      Surgery was performed during 4005 admissions. Output data from Karbase is
      presented with results on survival and postoperative complications, related to
      preoperative risk factors. The incidence of surgical wound infections was 3.9%,
      with a significant reduction during the years (p = 0.004). Karbase is now used by
      all vascular surgical units in Denmark. We conclude that the establishment of a
      continuous registration has been beneficial to the department. We have achieved
      valid data on treatment, outcome and complications in relation to individual risk
      factors. In the future the use of Karbase will be extended with the aim of
      further quality development, locally as well as nation wide.

PMID- 7817411
TI  - [Color Doppler ultrasound examination of carotid arteries].
AB  - Eleven hundred and thirty-eight patients suspected of carotid artery disease were
      examined prospectively by ultrasound-Doppler. In 39 cases, intra-arterial digital
      subtraction arteriography was performed as well as well and compared to
      ultrasound Doppler examination. The overall accuracy was 80% (kappa: 0.65).
      Discrimination between normal and diseased vessels could be made with an accuracy
      of 93% (kappa: 0.70) and the accuracy when separating vessels into greater or
      less than 50% stenosis was 88% (kappa: 0.74). Sources of error are discussed and
      the paper concludes that colour-Doppler examination is an accurate method for
      assessment of the carotid artery.

PMID- 7817412
TI  - [Recanalization of occluded coronary arteries with percutaneous transluminal
      coronary angioplasty].
AB  - Percutaneous transluminal coronary angioplasty (PTCA) was attempted in 56 totally
      occluded coronary arteries. The occlusions were estimated to be between two weeks
      to six months old, less than 4 cm long and accessible to PTCA. Primary technical
      success was achieved in 40 cases (71%) with best results if the time from AMI to
      PTCA was less than six months. Twenty-six patients were without recurrence in the
      follow-up period which was longer than six months. In the follow-up period eight
      patients had re-PTCA performed and six had coronary artery bypass grafting
      (CABG). There were significantly more patients in the group of failed PTCA who
      had CABG than in the group of successful PTCA. At clinical follow-up examination
      23 patients (41%) were free of symptoms and seven (13%) had less pain than before
      PTCA. One patient died in heart failure (mortality 1.8%) within 24 hours after
      failed PTCA. PTCA of totally chronically occluded coronary arteries is a method
      with acceptable good primary success, especially if the occlusion is not too old.
      There is a good symptomatic effect if the PTCA is successful. The procedure
      reduces the need for CABG and is associated with few complications in stable
      angina pectoris. PTCA is cheaper and less traumatic for the patients and with
      much shorter recovery period compared to CABG. PTCA is considered indicated in
      total chronic occlusions in selected cases.

PMID- 7817414
TI  - [Asymptomatic sexually transmitted infections among HIV-tested persons].
AB  - We have prospectively determined the frequency of asymptomatic sexually
      transmitted diseases (STD) among patients seeking an HIV-test. In 246 patients,
      we observed 32 cases (13%) of asymptomatic STD, predominantly infections caused
      by Chlamydia trachomatis or human Papillomavirus. STD screening is of
      significance among patients seeking an HIV-test.

PMID- 7817413
TI  - [Vascular surgery in patients with impaired renal function].
AB  - The purpose of the study was to evaluate the effect of surgery for renal artery
      stenosis in patients with impaired renal function. The design was a retrospective
      investigation with follow-up. The material consisted of 42 such patients operated
      at Rigshospitalet between 1980 and 1990. Renal function and blood pressure status
      was evaluated preoperatively and at follow-up. The perioperative mortality was 5%
      (n = 2) and morbidity 21% (n = 9). At discharge from hospital renal function was
      maintained in 38 patients (90%), including three patients who at the time of
      operation were without diuresis and had been in dialysis for up to 28 days.
      Twenty-three patients were still alive at postoperative follow-up at a median of
      66 months. The cumulative five-year survival was 62%, which was significantly
      lower than that of a sex- and age-matched population. Eleven patients developed
      terminal renal insufficiency during the follow-up period. The cumulative
      preservation of renal function was 77% after five years. In conclusion,
      reconstruction of the renal arteries in patients with declining renal function
      and renal artery stenosis or occlusion can save renal function such that dialysis
      may be avoided in most cases.

PMID- 7817415
TI  - [Purulent meningitis at the Marselisborg Hospital 1980-1990].
AB  - From 1980-1990 245 immunocompetent patients were admitted to The Department of
      Infectious Diseases, Marselisborg Hospital with purulent meningitis or
      meningococcal septicaemia. The clinical diagnosis was established by clinical
      examination and by neutrophil pleocytosis. The aetiological diagnosis was
      established by demonstration of bacteria in the cerebrospinal fluid by microscopy
      or culture and by blood culture. Clinical signs of disseminated intravascular
      coagulation (DIC) or demonstration of meningococcal antibodies (MAT) in serum
      were considered diagnostic for meningococcal disease. The group comprised 120
      males and 125 females aged 0-90 years. One hundred and eleven (45%) had
      meningococcal disease, 69 (28%) had pneumococcal meningitis, and 20 (8%) had H.
      influenzae-meningitis. Other aetiologies occurred in one to six cases. No
      aetiology could be established in 25 (10%) patients. Patients with meningococcal
      and pneumococcal disease were treated with monotherapy with high doses of
      penicillin, and H. influenzae-meningitis was treated with ampicillin. In patients
      with meningitis of unknown aetiology penicillin was used, except in children
      below the age of five where ampicillin was used. In patients with meningococcal
      disease the mortality was 5.4%, and 17% developed sequelae. In pneumococcal
      meningitis the corresponding figures were 13% and 17%, and in H. influenzae
      meningitis 0% and 5% respectively. Among 20 patients with other aetiologies one
      patient (5%) died, and eight (40%) developed sequelae, whereas one patient (4%)
      died, and one (4%) developed sequelae in the group with meningitis of unknown
      aetiology. No ampicillin-resistant H. influenzae-strains were demonstrated. We
      suggest that monotherapy with betalactam-antibiotics is still a valuable
      treatment for meningitis in Denmark.

PMID- 7817416
TI  - [Androgen insensitivity syndrome--testicular feminization--Morris syndrome. A
      surgical procedure in cases when a testis is found during herniotomy in a girl].
AB  - The androgen insensitivity syndrome is uncommon, but still the most frequent male
      pseudohermaphroditism. It is an X-linked recessive disorder characterized by
      androgen receptor defectiveness of various intensity. In the state of complete
      insensitivity, the male karyotype 46-XY develops a female gender with bilateral
      testes. Inguinal hernia is a common clinical presentation for a young child with
      complete androgen insensitivity. Thirty-five to forty percent of those with
      Morris syndrome come out with incarcerated hernias containing a testis, some even
      pass unnoticed at elective herniorraphy on apparently normal infant girls. It is
      recommended to perform orchiectomy when a testis is found during surgery.
      Subsequently the patient should be referred to major centres for further and
      thorough surveys.

PMID- 7817417
TI  - [Carbohydrate-deficient glycoprotein syndrome].
AB  - Carbohydrate-deficient glycoprotein syndrome is a recently identified recessively
      inherited, multisystemic disease with severe nervous system involvement. It is
      characterized biochemically by carbohydrate-deficient serum glycoproteins. Serum
      transferrin shows the most pronounced carbohydrate defect, and can be used as a
      marker of the disease. The patient we present here had many of the characteristic
      symptoms. She was a girl with psychomotor retardation, and had slightly
      dysmorphic features. She had convulsive episodes, some hepatopathy and
      pericardial effusions. CT-scan of the cerebrum showed cortical and central
      atrophy. The diagnosis was confirmed by the finding of greatly elevated values of
      carbohydrate-deficient serum transferrin.

PMID- 7817418
TI  - [Anterior lumbar intercorporal spondylodesis].

PMID- 7817419
TI  - [Obsessive-compulsive conditions--psychiatric or neurologic diseases?].

PMID- 7817420
TI  - [Virus encephalitis after tick bite].

PMID- 7817421
TI  - [Emergency pain service--exciting new thinking].

PMID- 7817422
TI  - [Possible severe consequences of epidural analgesia].

PMID- 7817423
TI  - [Acute pain service--another in-hospital specialty?].
AB  - Realizing that achievement in postoperative pain treatment was not satisfactory,
      central health authorities in USA, United Kingdom and Australia have published
      guidelines for managing acute pain. Establishing acute pain services is thought
      to be one of the means of improving pain relief in the individual patient.
      Development and research are secured and achieved results may be presented
      currently. At this moment, introduction of acute pain services is at a
      preliminary stage in Denmark, and consequently an overview of results obtained
      from abroad is given including pain treatment techniques, management and safety
      measures, as well as visions concerning the impact of optimal pain relief upon
      convalescence. We conclude that the introduction of acute pain services is bound
      to optimize postoperative patient care and might well prove to be a significant
      factor in reducing postoperative morbidity.

PMID- 7817424
TI  - [Reversibility test in obstructive lung disease. Use and limitations].
AB  - Spirometry is often repeated after administration of bronchodilators or
      corticosteroids as a reversibility test. This review focuses on the performance,
      the utility and limitations of these tests. The response to bronchodilators and
      corticosteroids is regarded as statistically significant if the increase in FEV1
      respectively exceeds 0.2 l and 0.35 l, but a higher improvement is probably
      necessary for clinical benefit. Response to corticosteroids is a characteristic
      feature of asthma, and most asthmatics will normalise their lung function or
      increase FEV1 by more than 0.5 l. A similar response to bronchodilators can be
      obtained in some asthmatics. Both tests are necessary for the patient with
      obstructive airway disease to determine the optimal lung function, and further
      therapy should be adjusted to reach this goal.

PMID- 7817425
TI  - [Herpes simplex infection in pregnant women and newborn infants].
AB  - The incidence of genital herpes infection is increasing. About 50% of infections
      in women are asymptomatic. Neonatal infection is the most serious complication of
      genital HSV-infection, the mortality being 70% if untreated. The incidence of
      asymptomatic HSV-infection in pregnant women at the time of giving birth is 0.2%.
      These women cannot be identified on the basis of clinical symptoms and medical
      history, and the diagnostic methods currently in use are not sufficiently
      sensitive for the screening of low risk groups. Pregnant women with primary HSV
      infection shed larger quantities of virus than women with recurrent infection,
      furthermore the foetus has not received passive immunisation by maternal antibody
      transfer. There is an increased risk of miscarriage, intrauterine infection and
      premature birth in connection with primary HSV-infection in pregnancy. Almost 50%
      of children born to mothers with primary HSV-infection at the time of birth
      become infected neonatally, compared with only 2-5% of children born to mothers
      with active recurrent HSV-infection. Recommendations are given for monitoring
      primary HSV-infection in the third trimester with viral cultures, monitoring
      recurrent HSV-infections clinically and indications for when delivery should be
      by caesarean section. Children born to women with active primary HSV-infection
      should be treated with antiviral agents. Children born to women with recurrent
      infection should have their secretions cultured for HSV.

PMID- 7817426
TI  - [Overheating and sudden infant death. Temperature regulation in relation to the
      prone position, the possible pathogenesis of sudden infant death].
AB  - The incidence of sudden infant death syndrome (SIDS) in Denmark varied in the
      period 1982-1991 between 1.5 and 1.9 per 1000 livebirths. In December 1991
      recommendations concerning infants' sleeping position were published by The
      Danish National Board of Health in order to reduce the risk of SIDS. Babies were
      recommended to be placed in the supine or side position when sleeping. Parents
      have followed the guidelines. Most Danish infants are now sleeping on their back
      or in the side position. Simultaneously, the number of SIDS dropped from about
      110 to 40 per year. The incidence decreased to 1.2 in 1992 and was further
      reduced in 1993 to 0.6 per 1000 live births. Referring to our knowledge of the
      infant's temperature regulation we discuss why the prone position is a risk
      factor for SIDS. The head is the site of up to 85% of heat loss in an infant in
      bed. Placed in the prone position, the infant is more likely to suffer a rise in
      body temperature, especially if this is combined with having a cold, being
      heavily wrapped and sleeping in a heated room. Preceding sudden death many
      infants are reported to have suffered from minor viral infections. These might
      per se increase the body temperature. Parents often wrap infants that have an
      infection too heavily, which in an infant sleeping in the prone position might
      increase the body temperature to a higher level than if sleeping supine. The body
      temperature influences the production of toxins from normal intestinal flora and
      from pathogenic bacteria.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7817427
TI  - [Smoking and sudden infant death].
AB  - Sudden Infant Death Syndrome (SIDS) is a death where autopsy and other
      examinations cannot explain the proper cause of death. Epidemiologic studies have
      recognized some risk factors, namely prone sleeping position, lack of breast
      feeding, overheating, and maternal smoking. In Denmark, the official
      recommendation concerning the prone sleeping position was changed in December
      1991, and since then the incidence of SIDS has been diminished by approximately
      60-70%. A large number of epidemiologic studies find that there is a possible
      risk for SIDS in connection with maternal smoking. The odds ratio for a pregnant
      smoker to lose an infant to SIDS is about 2-4. Thirty to forty percent of Danish
      women smoke during pregnancy, and about half of all children are exposed to
      passive smoking in their homes. These data show that about 20% of the SIDS cases
      are due to maternal smoking. Further information and individual advice to
      pregnant, smoking women and their partners are needed. The authors suggest that
      this advice should become part of the existing ante-natal care programme.

PMID- 7817428
TI  - [Cervical insufficiency and cerclage in Denmark 1980-1990. A registry-based
      epidemiological study].
AB  - The objective of this analysis was to assess the incidence rate of cervical
      incompetence diagnoses in Denmark 1980-1990 according to maternal age, to analyze
      regional variations, to investigate how often cervical cerclage is applied, and
      finally to estimate abortion rates among women with cervical incompetence with
      and without cervical cerclage. The design was a register-based retrospective
      cross sectional study, including all Danish gynaecological departments. Since
      1977, all hospitalized patients in Denmark have been centrally recorded by
      diagnosis according to the ICD classification and by operation codes in The
      National Patient Register. From this database, all women with cervical
      incompetence (CI) and cerclage in the period 1980-1990 were identified. From the
      same database all cases of spontaneous abortions were registered. A total of 2756
      cases of cervical incompetence were registered in the period 1980-1990,
      corresponding to an incidence rate of 4.6/1000 births. The risk of cervical
      incompetence increased from 2/1000 births among women 15-19 years old to 7.5/1000
      births among women 35-39 years old. The incidence rate of the CI-diagnosis fell
      by 44% from 1980 to 1990. The incidence rates in different counties ranged from
      1.7/1000 births to 10.0/1000 births. The average length of stay in hospital among
      patients with cervical incompetence was three weeks. Among patients with cervical
      incompetence, 61% were treated with cervical cerclage. This percentage increased
      from 29% among women 15-19 years old to 68% among women 35-39 years old. 13.5% of
      women with CI experienced spontaneous abortion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7817429
TI  - [Open tension-free hernioplasty using mesh in the treatment of inguinal hernia in
      adults].
AB  - Open tension-free inguinal mesh repair is a new operative procedure in Denmark.
      During 1993 the author performed 20 procedures in 19 men with inguinal hernias,
      of which seven were direct and 13 indirect. Five of the hernias were recurrent
      and one patient had bilateral hernias. The median operation time was 30 minutes
      from skin incision to closure. The recovery time was short and the complications
      were few and insignificant. No infections occurred. One patient operated for an
      indirect hernia complained of recurrency. Reoperation was performed
      laparoscopically and a femoral hernia, obviously overlooked at the primary
      operation, was found. There were no other recurrencies. Thus, tension-free open
      inguinal hernial repair seems to be a safe and easy procedure with few
      complications and no early recurrency.

PMID- 7817430
TI  - [Troponin T in acute myocardial infarction. Diagnosis and prognosis in patients
      admitted for suspected acute myocardial infarction].
AB  - Cardiac troponin T (TnT) is a new serological marker for use as a diagnostic tool
      for myocardial damage. A blinded prospective multicentre study representing 298
      patients who on admission were suspected of acute myocardial infarction (AMI) to
      the coronary care units of six Scandinavian hospitals was undertaken to assess
      the diagnostic performance and prognostic efficacy of a new cardiospecific TnT
      immunoassay. We used a discriminator value of TnT of 0.20 micrograms/l. One
      hundred and fifty-five patients (52%) had definite AMI, based on WHO criteria
      (all had peak S-TnT values > or = 0.20 micrograms/l); 127 patients (43%) had
      ischaemic heart disease (IHD) without AMI; and 16 patients (5%) had non-IHD (all
      had peak S-TnT values < 0.20 micrograms/l). The 127 IHD-patients without definite
      AMI could be subdivided into a group of 44 patients with S-TnT peak values > or =
      0.20 micrograms/l, and a group of 83 patients with TnT below this level. A follow
      up study was able to define the clinical significance of these findings. The
      cumulative six months probability of suffering cardiac death or AMI was
      significantly higher in the subgroup with increased TnT values (14% (6/44)) as
      compared to the other subgroup (4% (3/83)) (Log-rank test, p = 0.025). The
      probability of cardiac events was 15% for the patients with definite AMI. We
      conclude that increased troponin T in serum can detect a subgroup of IHD-patients
      in whom AMI has been ruled out, but who still have a prognosis as serious as that
      of patients with definite AMI.

PMID- 7817431
TI  - [A herbal preparation Resium in symptomatic gallstones. A preliminary study of
      the effect].
AB  - Resium, an old Spanish herb, is claimed to remove gallstone symptoms and to
      dissolve gallstones. Ten patients admitted for cholecystectomy because of
      intermittent bile cholics participated in a study for six months to evaluate the
      effects. None had had complications to their gallstone disease, and all had
      normal liver biochemistry and a normal well-functioning gallbladder before entry
      into the study. By ultrasonography minor changes in both directions in stone
      number and volume were seen. Five patients experienced some relief of symptoms,
      while the rest had unchanged, or worse symptoms. No adverse events to Resium were
      seen. In conclusion no effect of Resium upon gallstone size and volume was seen.
      The design of the study does not allow any conclusion about symptomatic effect to
      be drawn.

PMID- 7817432
TI  - [The association of alcohol and mortality. Significance of gender,age, weight and
      smoking].
AB  - The aim of the study was to examine the association between self-reported alcohol
      intake and subsequent mortality from all causes, and to examine if the effect of
      alcohol intake on the risk of death was modified by sex, age, body mass index,
      and smoking habits. In a prospective population study of 7,234 women and 6,051
      men aged 30-79 years alcohol- and tobacco consumption and body mass index were
      assessed in the period 1976-1978, and the population was followed until 1.1.1988
      for mortality. A U-shaped curve described the relation between alcohol intake and
      mortality. The nadir of the risk function was observed at one to six beverages
      per week (relative risk set at 1.00). Abstainers had a relative risk of 1.37 (95%
      confidence intervals: 1.20-1.56), whereas those drinking more than 70 beverages
      per week had a relative risk of 2.29 (1.75-3.00). Among the drinkers, the risk
      was significantly higher than 1 only among those drinking more than 42 beverages
      per week. Neither sex, age, body mass index, nor smoking significantly modified
      the risk function. Our findings suggest that simple messages about the benefits
      of total abstinence may not be appropriate.

PMID- 7817433
TI  - [Bone metabolism in female runners. Menstruation disorders are frequent among
      long-distance runners, but the bone mass is not influenced, with the exception of
      runners with amenorrhea].
AB  - The purpose of the study was to investigate the prevalence of exercise-related
      menstrual and sex hormonal disturbances and the effect of exercise on bone mass
      and metabolism in female runners at various training levels. Two hundred and five
      premenopausal women (running 0-140 km a week) were recruited from a large
      population of female runners, who had responded to a questionnaire regarding
      exercise habits. Maximum oxygen uptake was determined by treadmill testing.
      Gynaecological status was assessed on entries in a menstrual calendar and by
      transvaginal ultrasonography; and sex hormonal status was measured three times
      with 10-day intervals. Bone mass was measured in the lumbar spine, proximal
      femurs and total body by dual energy x-ray absorptiometry, and in the forearm by
      single photon absorptiometry. Bone turnover was assessed by plasma osteocalcin,
      serum alkaline phosphatase, and urinary calcium and hydroxyproline. The results
      showed that sex hormonal disturbances were significantly related to training
      intensity. Compared with the normally active women, the baseline levels and
      fluctuations of oestradiol and progesterone in the elite runners were reduced by
      up to 25-44%, (0.01 < p < 0.05). The prevalence of amenorrhoea increased from 1%
      in the normally active to 11% in the elite runners. No statistically significant
      relation was found between running activity and bone mass or bone turnover.
      However, the group of amenorrhoeic runners had a 10% reduction in lumbar bone
      mass as compared to the normally menstruating runners (p < 0.05), but the bone
      turnover was similar.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7817434
TI  - [Mortality--suicide and natural death--among depressed patients. Relation to type
      of depression].
AB  - A total of 219 inpatients with a DSM-III diagnosis of major depression, (150
      women and 69 men), were followed prospectively for three to ten years and
      mortality was recorded. The patients were previous participants in
      psychopharmacological multicentre trials, which were carried out for the purpose
      of comparing the antidepressant effect of newer selective serotonin reuptake
      inhibitors (SSRI), citalopram and paroxetine, with that of the tricyclic
      antidepressant drug, clomipramine. Diagnostic classification according to the
      Newcastle-I Scale into endogenous and nonendogenous depression was performed. The
      observed mortality was significantly greater than that expected. The increased
      mortality was essentially due to suicides and mainly found among women. Patients
      scored as being nonendogenously depressed had a significantly higher suicide rate
      than endogenously depressed patients. The excess number of suicides in the
      nonendogenous group largely occurred within the first year of observation. No
      association was found between response to the antidepressant treatment in the
      trial and the suicide risk during the first three years of observation.

PMID- 7817435
TI  - [Xanthomonas maltophilia. A cause of epidural abscess in a patient with epidural
      catheterization].
AB  - A case of epidural abscess following continuous spinal epidural catheterization
      is presented. The clinical signs included spinal ache, root pain, weakness and
      paralysis but no fever. Xanthomonas maltophilia, an organism closely related to
      Pseudomonas species, was the causative agent. This has not previously been
      described as the causative agent of epidural abscesses.

PMID- 7817436
TI  - [Atypical site of epidural hematoma--after epidural analgesia].
AB  - We report a case of epidural haematoma with an unusual position which was
      believed to be a sequela after placement of an epidural catheter in a 58-year old
      female. The catheter was inserted at level T12-L1 and the haematoma was found at
      level T5-7. The patient received heparin s/c 5000 IE x 2 immediately
      postoperatively. The clinical signs were atypical, with no backpain. We conclude
      that the development of symptoms is not necessarily related to the introduction
      of the catheter. In the actual case it is most likely that the symptoms had their
      origin from a spontaneous spinal epidural haematoma.

PMID- 7817437
TI  - [Failure of fluoroquinolone treatment in pneumococcal pneumonia].
AB  - Based on a case story concerning the development of pneumococcal pneumonia in
      relation to treatment with a quinolone, use of such antibiotics in respiratory
      tract infections is discussed. In the light of in vitro results, animal
      experiments, and clinical reports of treatment failure of quinolones, we warn
      against the routine use of these antibiotics against respiratory tract
      infections. Quinolones may be useful in the treatment of verified Gram-negative
      respiratory tract infections, but should always be preceded by susceptibility
      testing.

PMID- 7817438
TI  - [Asynchronous double-sided angle-closure glaucoma--a condition in an
      ipratropium/terbutaline treated patient under artificial ventilation].
AB  - A case is presented of an intubated, sedated patient, without previous eye
      problems, who developed acute angle closure glaucoma (AACG) after receiving
      nebulized terbutaline and ipratropium bromide for an acute exacerbation of
      chronic obstructive airway disease. When a patient under this treatment develops
      a fixed dilated pupil, as in this case, it is recommended to consider AACG among
      the possible causes.

PMID- 7817439
TI  - [Increased coronary enzymes among body builders].

PMID- 7817440
TI  - [Prognosis of low birth weight children].

PMID- 7817441
TI  - [The analgesic value of anti-arrhythmia agents].

PMID- 7817442
TI  - [Therapy and follow-up of superficial bladder cancer in in patients less than 30
      years of age].
AB  - Transitional cell carcinoma of the bladder is relatively uncommon in patients
      under 30 years old. We treated 11 patients with superficial bladder carcinoma
      under 30 years of age. In 10 cases gross haematuria was the most common
      presenting symptom. The pathological reports of the patients revealed grade I,
      stage Ta transitional cell carcinoma in seven patients, grade I, stage T1 tumour
      in two patients and bladder myoma and inverted papilloma in two patients each.
      Four of nine patients with superficial bladder carcinoma stayed free of disease
      for 1-10 years after initial transurethral resection (TUR). Four patients
      suffered multiple tumour recurrences 1-4 months after initial TUR, with
      progressive disease in three cases. One patient was lost to follow-up after
      primary operation. In the two patients with benign bladder tumours, no
      recurrences were observed within 12 and 48 months. Owing to the high rates of
      recurrence (44%) and tumour progression (33%) all patients under 30 years of age
      should be treated as aggressively as necessary on the basis of the grade and
      stage of the tumour, in the same way older patients.

PMID- 7817443
TI  - [Long-term results of intravesical prevention of recurrence with mitomycin C and
      adriamycin in patients with superficial bladder cancer].
AB  - In a prospective multicenter study, four protocols for administration of
      mitomycin C and Adriamycin by intravesical installation were evaluated for
      effectiveness in the prevention of recurrent tumours in patients whose
      superficial bladder tumours (TA and T1) had been removed by transurethral
      resection. The 3-year and short-term installation protocols were compared with
      each other and each with a combination of the two. Evaluation after a mean follow
      up of 62.5 months was possible in 333 patients: the overall recurrence rate was
      20.7% and the overall progression rate, 9.3%. No statistically significant
      differences were found in frequency of tumour recurrence among three mitomycin
      regimens and an Adriamycin regimen, regardless of the risk groups. However,
      frequency of recurrence per time unit was much lower in the treatment group with
      short-term intensive (weekly) mitomycin instillation, which was due mainly to
      prevention of late recurrence.

PMID- 7817445
TI  - [Bilateral ureteral rupture in a child after blunt trauma].
AB  - We report a case of bilateral subpelvic ureteral disruption in a child following
      blunt trauma sustained during a road traffic accident. This case illustrates the
      importance of coordinated interdisciplinary management in the primary diagnosis
      of patients with blunt abdominal trauma. The pathomechanism of traumatic ureteral
      avulsion is also discussed.

PMID- 7817444
TI  - [Rare metabolic and cerebral complications after polychemotherapy of a testicular
      tumor].
AB  - In a 21-year-old patient with a tumor of the right testis, CT indicated a
      pathologically altered lymph node in the interaortocaval region. After high
      inguinal orchiectomy we performed a modified retroperitoneal lymph node
      dissection and monitored its success by immediate section for microscopic
      examination. Pathohistological investigation yielded immature teratoma. The
      patient was given two courses of adjuvant polychemotherapy containing cisplatin.
      Two days after the conclusion of the second course he was readmitted with grand
      mal epilepsy and visual agnosia. Two months later another grand mal epileptic fit
      occurred. The patient also suffered from marked metabolic disorders, such as
      hypokalemia, hyperreninism, hyperaldosteronism, kaliuresis, and hypertension. We
      consider these to be toxic side effects of cisplatin resulting in nephropathy.
      Evidence of cisplatin-induced encephalopathy was obtained by NMR tomography and
      EEG which indicated barrier disorders. Symptoms were relieved and continuous
      normalization of blood pressure, potassium level, and water and electrolyte
      balance was achieved by the administration of potassium substitution, ACE
      inhibition, and an aldosterone antagonist. The patient has since remained in a
      stable condition.

PMID- 7817446
TI  - [Treatment of complicated recurrent hypospadias].
AB  - Between January 1985 and December 1990, a total of 40 patients aged 2-40 years
      underwent surgical reconstruction for complicated failure of hypospadias repair.
      These included 19 patients with multiple previous operations, severely scarred
      skin, penile deviation, long urethral defects and scarred or cleft glans, who
      were classified as hypospadias cripples (group I). The remaining 21 patients had
      distal urethral defects and a scarred or cleft glans but better skin condition;
      this group was classified as having defects of the distal urethra and glans
      (group II). Island flaps were used in 17 patients, and transversal or axial
      random penile skin flaps in 18. In 4 patients the urethra was reconstructed with
      mesh graft and in 1 case, with a bladder mucosa graft. With the designed single
      session procedure primary treatment was successful and free of complications in
      52% of the patients in group I and 67% in group II. In each of 3 patients three
      further operations were required. In 15 patients revision surgery was confined to
      simple fistula closure, stricture incision or correction of scarred skin. Follow
      up examination at 7-72 months showed that treatment had been successful in all
      patients.

PMID- 7817447
TI  - [Morphologic results of 106 consecutive radical prostatectomy specimen of
      patients with clinical stage B1-B3 (T2a-c) and histologically negative lymph
      nodes in the fossa obturatoria].
AB  - The morphologic results recorded in 106 consecutive radical prostatectomy
      specimens from patients with clinical stage B1-B3 (T2a-c) are presented. All
      specimens had inked margins and were subjected to morphometric work-up using a 3
      mm step section technique. In only 39 (37%) was the tumour confined to a single
      organ (pT2); 67 (63%) were stage pT3; 40 (37.7%) had only capsular penetration;
      and 27 (25.4%) had seminal vesicle invasion. In 33 (31.1%) the surgical margin
      was positive. None of those with pathological stage pT2 had a positive margin. Of
      the 40 patients with pathological stage pT3a+b, 19 (47.5%) had a positive margin.
      Of the 27 patients with seminal vesicle invasion (pT3c), 14 (51.8%) had a
      positive margin. Specimens with only unilateral seminal vesicle invasion or none
      at all had positive surgical margins in only 25% and 24% of cases, in contrast to
      those with bilateral seminal vesicle invasion, in which the rate for positive
      margins was 73%. The mean tumour volume was 8.1 cm3 (0.12-50.13 cm3). There were
      9 (8.4%) tumours with a volume < 0.5% cm3 while 62 specimens contained > 0.5 cm3
      Gleason 4 and Gleason 5 tumours. Our analysis shows a good correlation of the
      positive margin rate with tumour volume and especially with volume of the high
      grade tumor.

PMID- 7817449
TI  - [Current status of extracorporeal shockwave lithotripsy].
AB  - Extracorporeal shockwave lithotripsy has become an established standard procedure
      for the treatment of nephrolithiasis. Almost 100 lithotripters are installed in
      large and medium-sized urological departments in Germany. The number of
      treatments per year averages 660 ESWL sessions per hospital. Multifunctional use
      and non-urological ESWL therapy ensure maximum utilization of the lithotripter
      units. In additional hospitals mobile lithotripsy is provided. At present there
      is a trend toward ambulatory ESWL treatment.

PMID- 7817448
TI  - [Surgical interventions of the adrenal gland. Diagnosis and results of
      treatment].
AB  - From 1982 to 1992, 33 patients underwent adrenalectomy for disease of the adrenal
      gland: 18 patients with adrenal cortex adenoma or hyperplasia (Cushing's syndrome
      n = 11, Conn's syndrome n = 6, adrenogenital syndrome n = 1), 3 with pituitary
      dependent Cushing's disease, 7 with pheochromocytoma (malignant n = 1), 2 with a
      metastasis of lung cancer and 1 with cystic adrenal necrosis. Multiple endocrine
      neoplasia existed in four cases. Various preoperative symptoms were noted,
      including complaints typical of the respective syndromes and general abdominal
      symptoms. Other patients were symptom-free with incidental findings. An
      intercostal approach was used in 30 cases, a transabdominal approach in 3 cases.
      In 6 cases bilateral and in 27 cases unilateral adrenalectomy was performed. In
      two cases additional nephrectomy became necessary because of extensive adhesions.
      Intraoperatively, one patient suffered a blood pressure crisis. 31 patients are
      still alive and symptom-free after a mean follow-up of 5.4 years (range 1-11
      years). Two patients have died (one with benign pheochromocytoma and one with a
      metastasis of lung cancer). Detailed preoperative hormone analysis and adequate
      preoperative medication substantially lowers the risk involved in adrenal
      surgery. However, the indications for surgical treatment of hormonally inactive,
      symptom-free adrenal tumors that are found incidentally remain controversial, and
      surgery should perhaps be restricted to large tumors.

PMID- 7817450
TI  - [Therapy of primary testicular chondrosarcoma].
AB  - We describe the clinical course in a patient with a primary testicular
      chondrosarcoma. The way of metastasizing and cytogenetic analysis proved the germ
      cell origin of this tumour. After unilateral orchiectomy four cycles of
      chemotherapy with cisplatin, etoposide and bleomycin and one cycle of
      vinblastine, ifophosphamide and cisplatin were given. Even though the
      retroperitoneal metastases continued to grow, a radical retroperitoneal lymph
      node dissection was performed. Five years after surgery the patient is still in
      remission.

PMID- 7817451
TI  - [Medical ethical aspects of the ambivalence to medical progress].

PMID- 7817453
TI  - [Superficial bladder cancer. Open questions].
AB  - Some important topics on basic research and clinical aspects of superficial
      bladder cancer are discussed: open questions include the prognostic relevance of
      several new biological markers that will have to be compared in clinical trials.
      Even established therapeutic procedures have to undergo critical analyses with
      regard to the stage-related optimal treatment. Recurrence prophylaxis in
      superficial bladder cancer is beset by many open questions relating to the
      therapy of choice, the optimal schedule and the quality of life of the patients
      affected.

PMID- 7817452
TI  - [Implementation of clinical urological studies and therapy trials using GCP (good
      clinical practice) guidelines].

PMID- 7817454
TI  - [Cytokine therapy of superficial bladder carcinoma. Mechanisms of action and
      results of therapy].
AB  - The object of immunotherapy is the elimination of tumor cells mediated by
      modulation of the immune system. This can be achieved by different mechanisms,
      i.e. cell-mediated and humorally mediated immune reactions. Immunotherapy can be
      classified as passive, adoptive, active and non-conventional. Most clinical
      experience has been gathered with unspecific active immunotherapy. Superficial
      bladder carcinomas can be treated by intravesical application of Bacillus
      Calmette-Guerin (BCG) or of different cytokines, i.e., interferons or interleukin
      2. Since there has not so far been any standard immunotherapy for superficial
      bladder carcinoma, the efficacy of therapy with cytokines should be evaluated in
      clinical studies (phase II/III) only.

PMID- 7817455
TI  - [Photodynamic procedures in urology].
AB  - Photodynamic therapy (PDT) has been demonstrated to be an effective therapy for
      carcinoma in situ of the urinary bladder. The data recorded in the various pilot
      studies are not comparable, because different photosensitizers, various
      irradiation modalities and different doses of photosensitizers have been used.
      Present activities include basic research on principles of action of PDT, the
      development of photosensitizers with better tumor selectivity, optimization of
      irradiation modalities, and prospective randomized clinical trials, e.g. in
      superficial bladder cancer. Photodynamic fluorescence diagnosis (PDD) can be
      performed easily in clinical conditions with the use of the topically applicable
      fluorescent marker delta amino levulinic acid (ALA). There is a need for
      controlled clinical trials to check the efficacy suggested for PDD by the very
      promising data yielded by pilot studies.

PMID- 7817456
TI  - [Unconventional therapeutic methods in superficial bladder cancer].
AB  - Several unconventional agents or methods are used for recurrence prophylaxis of
      superficial bladder cancer. In animal experiments KLH (keyhole limpet hemocyanin)
      has shown an effect comparable to that of BCG on bladder carcinoma, resulting in
      an increase of natural killer cell activity. The few clinical data dealing with
      KLH are contradictory. A prospective randomized study with a large number of
      patients uniform high dosage and early start of instillation has not yet been
      performed for definitive evaluation of the clinical role of KLH. Whether
      mistletoe extracts or intravesical antineoplastic iontophoresis can prevent
      recurrence is not yet known. Vitamin A and megadose multivitamins in combination
      with intravesical BCG significantly decrease the recurrence rate. The most
      effective vitamin or the most important combination has not yet been identified,
      and the precise mechanism of action is also unknown.

PMID- 7817457
TI  - [Chemotherapy of bladder carcinoma. Current status and trends].
AB  - Cisplatin and methotrexate are the most effective single agents used in the
      chemotherapy of metastatic transitional cell carcinoma. These agents should be
      included in polychemotherapy regimens. Polychemotherapy, especially with MVAC,
      leads to improved rates of complete remission. The attainment of complete
      remission has a statistically significant association with duration of survival.
      However, after 5 years there is no further survival advantage. If one quarter of
      patients achieve a CR, with a duration of more than 3 years in only half of them,
      a durable response can be expected in only 13% of treated patients. That means a
      maximal therapeutic benefit of 10-15% in polychemotherapy of bladder cancer,
      which is associated with relatively high toxicity. Prospective randomized trials
      are needed to determine the efficacy of treatment with two versus four agents.
      Dose intensification of the agents in the MVAC regimen has not resulted in
      significant improved remission rates. This approach is also limited by the
      appearance of non-haematotoxic side effects.

PMID- 7817458
TI  - [Adjuvant polychemotherapy after radical cystectomy of metastatic bladder
      cancer].
AB  - The aim of adjuvant polychemotherapy after radical cystectomy for patients with a
      high risk of tumor progression is to improve cure rates or at least prolong
      survival. So far, three prospectively randomized and several retrospective
      studies analyzing the benefit of adjuvant polychemotherapy have been performed.
      All have revealed longer survival times after adjuvant chemotherapy. The up-dated
      data from our own study increasingly suggest that a significant improvement of
      tumor-free survival rates is also possible, which is in accordance with the
      retrospective studies published so far. The extension of lymph node involvement,
      however, seems to be the most important independent prognostic variable. Further
      studies are necessary to define therapy-specific risk groups and the potential
      therapeutic benefit in the different groups. The optimal chemotherapy combination
      and the optimal dosage also remain to be defined.

PMID- 7817459
TI  - [Neoadjuvant chemotherapy of invasive bladder cancer].
AB  - Neoadjuvant chemotherapy is defined as cytotoxic treatment of an invasive
      carcinoma of the bladder. It is primarily suitable for a curative cystectomy with
      the aim of improving the therapeutic chances of the definitive treatment (i.e.,
      cystectomy, radiotherapy) by devitalization of the primary tumor and effective
      control of micrometastases. Thus, one of the major goals is preoperative
      sterilization of the tumor (stage pT0) to avoid tumor cell seeding during
      surgery. Until now, the documented pathological complete response rate (CRp)
      after 2-4 cycles of polychemotherapy has ranged from 19 to 38% plus 3 to 23% of
      complete surgical response (CRs) with residual superficial bladder tumors in the
      cystectomy specimen. The survival rates following neoadjuvant polychemotherapy
      differ considerably between 54 and 82% independent of the definitive treatment
      (cystectomy, radiotherapy). However, the response to chemotherapy has a
      significant impact on survival: patients with major pathological response (CRp +
      CRs) yielded a 75-100% disease-free survival after 4 to 5 years in contrast to 20
      22% for partial or non-responders. Future studies should investigate methods
      predicting the outcome of polychemotherapy (i.e., identifying mdr-chemoresistant
      tumors by detection of P170 glycoprotein in the TUR specimen) or improving the
      reliability of preoperative diagnosis (clinical = pathological complete
      response).

PMID- 7817460
TI  - Incidence and level of seminal reactive oxygen species in normal men.
AB  - OBJECTIVES: Excessive formation of reactive oxygen species (ROS) in human semen
      has been associated with impaired sperm function and fertility potential. The
      presence of ROS in semen specimens from normal fertile men emphasizes the
      importance of defining a normal range of ROS formation. The purpose of this study
      was to establish a normal range of ROS generation and to investigate the effect
      of sperm concentration on the ROS level. METHODS: ROS was determined in 15
      healthy donors and 20 men with suspected infertility. After the sperm
      concentration in normal donors was adjusted to 20 x 10(6)/mL, ROS was measured by
      chemiluminescence using luminol in a Berthold luminometer. A specimen was
      regarded as positive (abnormal) when the value was at least 10 x 10(4) counts per
      minute (cpm). ROS was also evaluated at 4 sperm concentrations (60, 30, 15, and
      7.5 x 10(6)/mL) from samples obtained from the patients with suspected
      infertility. In addition, ROS was measured in 7 ROS-positive specimens at a sperm
      concentration of 15 x 10(6)/mL and 60 x 10(6)/mL. RESULTS: Results showed that
      ROS formation was negative in all 15 healthy donors (median, 0.9 x 10(4) cpm;
      interquartile range, 0 to 1.48 x 10(4) cpm). The ROS formation value among all
      the donors was less than 5.5 x 10(4) cpm. ROS formation was positive in 8 (40%)
      of the suspected infertile patients. ROS levels were significantly lower at sperm
      concentrations of 15 x 10(6)/mL or 7.5 x 10(6)/mL compared with 30 x 10(6)/mL or
      60 x 10(6)/mL (P = 0.05). The ROS level increased after centrifugation for 10
      minutes at 500 g in all 7 specimens at both 15 and 60 x 10(6)/mL. However, the
      increase in ROS formation at 60 x 10(6)/mL was significantly greater than that at
      15 x 10(6)/mL (P < 0.001). CONCLUSIONS: A range of ROS formation of 0 to 5.5 x
      10(4) cpm at a sperm concentration of 20 x 10(6)/mL may be considered as normal
      for healthy donor semen. The positive relationship between ROS formation and
      sperm concentration at the time of measurement emphasizes the importance of
      concentration adjustment before analysis when comparing ROS levels between
      different specimens.

PMID- 7817461
TI  - Urinalysis, ultrasound analysis, and renal dynamic scintigraphy in acute
      appendicitis.
AB  - OBJECTIVES: The influence of acute appendicitis (AA) on the right kidney and
      urinalysis was investigated. Permanent damage of the urinary tract and abnormal
      urinalysis have been previously reported in AA. METHODS: Appendectomy was
      performed in 84 patients with no previous urogenital, retroperitoneal, or pelvic
      disease, trauma, or operation. AA was confirmed in 66 of them. Control groups
      were the remaining 18 patients and 40 patients with varicocele repair. Renal
      sonography and urinalyses were done prior to operation, on days 1, 3, and 6
      postoperatively. Pentetic acid renal scintigraphy was done on postoperative day 1
      in patients with abnormal urinalysis. An obstructive radiographic curve indicated
      furosemide renography. RESULTS: Abnormal urinalysis was found in 48% of patients
      with AA before appendectomy and in 12% on day 6 postoperatively. Sonography
      showed pyelocaliceal dilation of the right kidney in 38% of patients with AA
      prior to appendectomy and in none on day 6 postoperatively. Patients with AA had
      pyelocaliceal dilation of the right kidney more frequently than those in the
      control groups (P < 0.001). It was more frequent in patients having abnormal
      urinalysis (P < 0.01). Scintigraphy confirmed pyelocaliceal dilation of the right
      kidney in 38% of patients with abnormal urinalysis. Furosemide renography
      excluded an obstruction in all of them. CONCLUSIONS: Inflammation is the major
      cause of abnormal urinalysis and transitory pyelocaliceal dilation in some
      patients with AA. Erythrocyturia, pyuria, proteinuria, and pyelocaliceal dilation
      detected by sonography or scintigraphy can frequently be found in patients with
      AA, but should not mislead the surgeon in the diagnosis of AA.

PMID- 7817462
TI  - Pelvic floor muscle exercises: 5 years later.
AB  - OBJECTIVES: To determine the outcome of pelvic floor muscle exercises for genuine
      stress incontinence after 5 years. METHODS: Questionnaires were sent to 48 women,
      mean age 57 years, with troublesome stress incontinence treated as outpatients by
      a skilled female physiotherapist to elucidate a self-assessment of therapy
      outcome and to determine patients' compliance concerning fulfillment of home
      exercises and attitude toward physiotherapy. Patients' self-assessment responses
      indicated cured, much improved, some improvement, or unchanged/worse and
      incidence of anti-incontinence surgery after physiotherapy. RESULTS: The overall
      cure/much improvement rate for physiotherapy at the end of therapy was 54% and 5
      years later it was 58% (confidence interval, 43 to 72); (P = 1.000, binomial
      test). Thirteen women (27%) underwent surgery. Seven unoperated women (15%)
      showed only some improvement or relapse and may have been undertreated. Severity
      of symptoms before therapy was an important factor in therapy outcome but not in
      therapy maintenance. Frequency of home practicing was comparable in those who had
      surgery afterward and those who had not. There was no clear linear relationship
      in long-term effect and frequency of home practicing. Severity of symptoms and
      behavioral changes bias this relationship. Physiotherapy was well tolerated, as
      73% would still prefer it as first choice. Pelvic floor muscle exercises were
      recommended to friends or relatives by 77% of the patients. CONCLUSIONS: Once a
      certain level of incontinence is established with pelvic floor muscle exercises,
      that level is maintained over 5 years.

PMID- 7817463
TI  - Nuclear morphometric analysis of metastasis in Wilms' tumor after multimodal
      therapy: comparison with primary tumor.
AB  - OBJECTIVES: The outlook for children with Wilms' tumor has improved with the use
      of multimodal therapy, and survival rates now exceed 85%. Yet, 15% of children
      with tumors with favorable histologic findings continue to recur unpredictably.
      We previously reported that nuclear morphometry (the distribution of nuclear
      roundness factor [NRF], lowest values for ellipticity, and age) when combined in
      a multivariate analysis accurately predicted response to therapy for patients
      with histologically favorable Wilms' tumors. METHODS: To investigate further the
      nuclear shape changes associated with disease recurrence, we analyzed histologic
      sections taken from primary tumors and postmultimodal therapy metastatic lesions
      for 7 children who had a recurrence with initially histologically favorable
      primary tumors. RESULTS: Mean NRF was significantly lower (P = 0.0001) in the
      metastatic lesion (35 +/- 5) group when compared with the primary tumor group (50
      +/- 5). The percent coefficient of variation for NRF was also significantly lower
      (P = 0.006) in the metastatic lesion when compared with the primary tumor.
      Nuclear area was increased (P = 0.02), although the nuclear perimeter was
      unchanged (P = 0.1). CONCLUSIONS: (1) Nuclei in metastatic lesions from Wilms'
      tumors with favorable histologic findings after multimodal therapy are more round
      and exhibit less variable distribution, suggesting clonal homogeneity within the
      metastatic lesion. (2) Nuclei in the metastatic lesions have greater area than in
      the primary tumors yet have an unchanged perimeter, which may be due to internal
      nuclear expansion secondary to increased cellular deoxyribonucleic acid (DNA)
      ploidy. Although the results of this study are promising, we are currently
      extending this hypothesis to a larger group of patients.

PMID- 7817465
TI  - Genitourinary manifestations of the acquired immunodeficiency syndrome.
AB  - As the number of HIV-1 infected individuals and AIDS patients continues to
      increase, more cases involving the genitourinary tract will be encountered.
      Often, genitourinary manifestations will be the initial presentation of AIDS.
      Proper diagnosis will require awareness and a high index of suspicion. In
      addition to routine cultures, opportunistic infections with unusual organisms
      will require staining for fungi and acid-fast bacilli. Repeat cultures of blood,
      urine, seminal fluid, and abscess cavities may be required to establish a
      diagnosis. Prolonged courses of antibiotic treatment for prophylaxis and for
      relapses are usually required. Clinical understaging and rapid progression of
      tumors distinguish HIV-1-associated malignancies involving the genitourinary
      tract. Treatment for these malignancies will depend on the stage of HIV-1
      infection. Any concomitant drug therapy and evidence of malnutrition will be
      important factors in selecting the proper timing and mode of therapeutic
      intervention. Although AIDS predominantly affects individuals between 30 and 50
      years of age, an increasing percentage of patients over 50 years of age are being
      diagnosed. Common risk factors for acquisition of HIV include homosexuality or
      bisexuality and transfusion of blood or blood products. For the urologist, it is
      important to recognize that older patients more frequently present with AIDS at
      the time of diagnosis of HIV infection. A more rapid course of deterioration and
      high mortality is noted in this population. Clearly, protocols including
      surveillance, dosing regimens, and surgical intervention will need to be
      established and clarified to treat an anticipated increasing number of affected
      patients. In addition, it appears that adequate adherence to universal
      precautions is far from being achieved. Close monitoring and active surveillance
      of infection control may be needed to improve compliance.

PMID- 7817464
TI  - Seromuscular colocystoplasty lined with urothelium: experience with 16 patients.
AB  - OBJECTIVES: Report of initial clinical experience with seromuscular
      colocystoplasty lined with urothelium (SCLU), a new operation to increase bladder
      capacity and compliance without incorporating intestinal mucosa into the urinary
      tract. We have previously reported the technique and results of this procedure in
      a canine model. METHODS: Sixteen patients underwent SCLU at two institutions.
      Their charts were reviewed retrospectively. The patients have been observed for a
      mean of 12 months. RESULTS: Postoperatively, the bladder capacity increased an
      average of 2.4-fold from a mean of 139 mL (+/- 23.7 SEM) to 335 mL (+/- 38.9 SEM)
      in 14 patients (P < 0.001). Two patients required reaugmentation. Preoperative
      and postoperative bladder end filling pressures were available in 13 patients and
      decreased from a mean of 51.6 cm H2O (+/- 4.2 SEM) to 27.7 cm H2O (+/- 2.4 SEM)
      (P < 0.001). Of the 16 patients, 13 were incontinent preoperatively; 5 had renal
      insufficiency. Three patients have undergone renal transplantation following
      SCLU. After SCLU, 13 patients were dry day and night, 1 incontinent at night
      only, and 2 remained incontinent. Ten patients have undergone postoperative
      bladder biopsy. Seven demonstrate urothelium covering the augmented portion of
      the bladder, 2 have regrowth of colonic mucosa, and 1 shows a mixture of colonic
      mucosa and urothelium. CONCLUSIONS: The results presented suggest that SCLU is a
      viable alternative to the more conventional forms of bladder augmentation in
      selected patients.

PMID- 7817466
TI  - Fibrous hamartoma of infancy: a report of two cases in the genital region.
AB  - OBJECTIVES: Fibrous hamartoma of infancy (FHI) is an uncommon subcutaneous
      proliferative lesion usually found in the upper portions of the body,
      particularly in males during the first 2 years of life. We report 2 cases of FHI
      in the genital region. METHODS: We retrospectively reviewed the charts of
      children treated at Children's Hospital and Health Center, with FHI located in
      the genital region. RESULTS: We report 2 cases of FHI in the genital region, 1
      involving the scrotum and 1 the labium majus. CONCLUSIONS: FHI should be
      considered in the differential diagnosis of genital masses in children. The
      histologic features are characteristic, local excision of the tumor is curative,
      and the local recurrence rate is low.

PMID- 7817467
TI  - Modified dartos pouch orchiopexy.
AB  - Experimental evidence suggests that transparenchymal suture fixation may risk
      testicular damage. Even very small sutures can result in inflammation and tubular
      damage. An alternative to transparenchymal suture fixation of the testis is
      presented.

PMID- 7817468
TI  - Hypercalcemia and urologic malignancies.
AB  - Hypercalcemia may be a manifestation of a variety of disorders including
      hyperparathyroidism, hypervitaminosis D, sarcoidosis, multiple myeloma,
      hyperthyroidism, acute osteoporosis, metastatic bone disease, and a number of
      primary malignancies. Hypercalcemia may be seen in as many as 1.5% of all
      patients with malignant disease, with or without bony metastases. The neoplasms
      most commonly associated with hypercalcemia include carcinoma of the lung (all
      cell types), breast cancer, squamous cell carcinomas, hematologic malignancies,
      and renal cell carcinoma. Observation of a number of instances of hypercalcemia
      attendant on urologic malignancies prompts the brief report of 4 characteristic
      cases with documentation of response to therapy. Management of severe and
      debilitating hypercalcemia is emphasized. Urologists should be aware of new
      agents available for such treatment.

PMID- 7817469
TI  - Idiopathic renal infarction.
AB  - We describe the course of acute renal infarction, without a demonstrable cause,
      in an otherwise healthy young male. Renal function was not compromised, and the
      infarct failed to progress. Literature on relevant diagnostic and therapeutic
      modalities is reviewed.

PMID- 7817470
TI  - Femoral neuropathy complicating urologic abdominopelvic procedures.
AB  - We report on 3 cases of femoral neuropathy following radical surgery for urologic
      malignancy. The defect was bilateral in 2 patients. Compression from self
      retaining retractors was the presumed mechanism of injury in all patients.
      Spontaneous improvement was observed in each case although the symptoms did not
      resolve completely. The pathophysiology contributing to this operative
      complication as well as measures for prevention and treatment are discussed.

PMID- 7817471
TI  - Enuresis in an adult female with obstructive sleep apnea.
AB  - Adult onset enuresis accompanied by obstructive sleep apnea has been reported
      rarely. A female patient was referred to our clinic with complaints of of a 15
      year history of loud snoring and sleep apnea as well as enuresis, which was
      treated successfully with imipramine and acetazolamide. The mechanism of enuresis
      and its relationship to upper airway obstruction are reviewed here with reference
      to the findings of polysomnography and sleep cystometry.

PMID- 7817472
TI  - Postoperative myocardial infarction after radical cystoprostatectomy masked by
      patient-controlled analgesia.
AB  - We present a case report where improper patient use of patient-controlled
      analgesia (PCA) in the postoperative period resulted in a significant delay in
      diagnosis of a postoperative myocardial infarction. Despite its excellent safety
      record and documented efficacy in controlling pain, PCA does have its limitations
      and can present a danger to the patient if operator error, patient error, or
      mechanical errors occur. Although the latter is rarely of concern, the two former
      possibilities exist. Other reported complications of PCA are discussed. We
      recommended that physicians, when considering use of patient-controlled
      anesthesia, discuss the qualitative and quantitative aspects of pain associated
      with the particular type of surgery performed to avoid missed postoperative
      complications.

PMID- 7817473
TI  - Epispadias with phimosis: an unusual variant of the concealed penis.
AB  - An unusual variant of concealed penis is described. Two neonates with epispadias
      and complete phimosis were diagnosed at birth and underwent delayed repair. These
      2 cases are the 5th and 6th such reports in the literature. This anomaly's
      possible embryogenesis is reviewed.

PMID- 7817474
TI  - Laparoscopic excision of a urachal cyst.
AB  - OBJECTIVES: To determine the role of laparoscopic surgery in the treatment of
      urachal disorders. METHODS: A case report and literature review of laparoscopic
      urachal cyst procedures. RESULTS: A 21-year-old man presented with a draining
      sinus at the umbilicus. A diagnosis of a urachal sinus was made. The patient
      underwent a laparoscopic excision of the sinus and cyst. CONCLUSIONS: Minimally
      invasive techniques such as laparoscopic surgery are the preferred means of
      managing urologic diseases such as the urachal cyst.

PMID- 7817475
TI  - The multicystic dysplastic kidney.

PMID- 7817476
TI  - Urethral warmer survey.

PMID- 7817477
TI  - Making the most out of six systematic sextant biopsies.

PMID- 7817479
TI  - Resolution time of Escherichia coli cystitis is correlated with levels of
      preinfection antibody to the infecting Escherichia coli strain.
AB  - OBJECTIVES: A number of studies in animals have demonstrated that immunization
      against uropathogenic bacteria can lessen the severity or duration of induced
      urinary tract infections (UTI). This study examined whether preinfection levels
      of serum or urinary anti-Escherichia coli antibodies were correlated with length
      of time needed to resolve an induced E coli cystitis. METHODS: Serum and urine
      anti-E coli antibody levels in 36 control and 42 vaginally immunized cynomolgus
      monkeys were measured by enzyme-linked immunosorbent assay. Regression analyses
      were used to determine correlations between resolution time and preinfection
      antibody level, and to estimate antibody levels that might be associated with
      effective resolution of an E coli UTI. RESULTS: Linear regression analysis showed
      significant correlations between short resolution time and high levels of serum
      immunoglobulin M (IgM), urinary secretory IgA, and urinary IgG specific for the
      infecting E coli strain. Serum IgM and urinary IgG anti-E coli levels in monkeys
      that cleared infections early were significantly higher than in animals with
      protracted infections. Logistic regression estimated the serum IgM and urinary
      IgG anti-E coli levels associated with a 50% probability of accelerated clearance
      to be 3.3 micrograms/mL and 2.7 micrograms/24 hours, respectively. CONCLUSIONS:
      For this primate model, the observed correlations between short resolution time
      and pre-existing serum and urinary antibody suggest that antibody-mediated
      immunity is an important component of host defense against UTI.

PMID- 7817480
TI  - Muscularis mucosa differentiates two populations with different prognosis in
      stage T1 bladder cancer.
AB  - OBJECTIVES: Contrary to previous belief, the existence of a muscularis mucosa in
      the human urinary bladder has now been well described. Although the degree of
      development of this structure seems variable, it can frequently be used to
      differentiate two levels within the subepithelial connective tissue: the lamina
      propria and the submucosa. The present study evaluates whether this morphologic
      feature is potentially useful for the identification of two populations with
      Stage T1 bladder cancer: those with tumor invasion confined to the lamina propria
      (pT1A) and those with tumors infiltrating into the submucosa (pT1B). METHODS: A
      series of 170 Stage T1 papillary bladder tumors was analyzed pathologically to
      identify the level of subepithelial connective tissue invasion. Both the
      reproducibility of such a differentiation and its prognostic implication were
      evaluated using Kaplan-Meier survival estimates and the Cox regression model.
      RESULTS: In specimens from transurethral resection, categorization into T1A or
      T1B could be performed in 98 of 170 cases (58% of specimens). Such
      differentiation proved to be of prognostic value with significantly different 5
      year survivals between the two subcategories (pT1A [n = 50] vs pT1B [n = 49])
      (log-rank, P < 0.02). Cox's regression analysis of pT1 subcategory and grade was
      performed in the 99 cases in which the differentiation between pT1A/pT1B could be
      made. This demonstrated that the depth of subepithelial connective tissue
      invasion was an independent prognostic factor (P < 0.05). CONCLUSIONS: The depth
      of tumor infiltration can be assessed in a considerable proportion of Stage T1
      bladder neoplasms. The present study validates the prognostic significance of
      such a distinction both by Mantel-Haenszel life table method and Cox's regression
      analysis.

PMID- 7817478
TI  - Management of small unilateral renal cell carcinomas: radical versus nephron
      sparing surgery.
AB  - OBJECTIVES: There is controversy concerning the management of small unilateral
      renal cell carcinomas. The present study was undertaken to evaluate the relative
      efficacy of radical nephrectomy versus nephron-sparing surgery in such patients.
      METHODS: Patients with a single, small (less than 4 cm), localized, unilateral,
      sporadic renal cell carcinoma (RCC) were identified from an institutional
      registry. From 1975 to 1992, 88 patients fulfilling these criteria were treated
      with either radical nephrectomy (n = 42) or nephron-sparing surgery (n = 46). The
      mean postoperative follow-up interval is 48 +/- 29 months. RESULTS: The radical
      and nephron-sparing surgical groups were well matched for patient age, sex, renal
      function, diabetes, hypertension, tumor size, tumor location, and tumor stage.
      All patients in both groups had low pathologic stage RCC. There was no difference
      between the two groups in terms of the mean hospital stay, the requirement for
      blood transfusions, or the occurrence of surgical complications. There was no
      difference in the mean preoperative and postoperative serum creatinine levels for
      patients in the nephron-sparing surgery group. However, the mean postoperative
      serum creatinine levels were significantly higher than the mean preoperative
      levels for patients in the radical nephrectomy group (P < 0.001). A single
      patient in each group developed recurrent RCC postoperatively. The cancer
      specific 5-year survival rate for patients in the radical and nephron-sparing
      surgical groups is 97% and 100%, respectively. CONCLUSIONS: Radical nephrectomy
      and nephron-sparing surgery each provide safe and effective curative treatment
      for patients with a single, small, unilateral localized RCC. The long-term renal
      functional advantage of nephron-sparing surgery in this setting is not
      established.

PMID- 7817481
TI  - Long-term monitoring of 486P 3/12 antigen pattern (quantitative immunocytology)
      before, during, and after mitomycin C prophylaxis in patients with superficial
      bladder cancer.
AB  - OBJECTIVES: Quantitative pattern of 486p 3/12 antigenicity in urine cytologies
      (Quic) of patients with superficial bladder carcinoma during operation and
      chemoprophylaxis was evaluated to determine the duration of prophylaxis on an
      individual patient-oriented basis. METHODS: Thirty-six patients with superficial
      bladder carcinoma during chemoprophylaxis (43 [range, 3 to 90] weeks of mitomycin
      C) have been evaluated monthly for 99 (range, 36 to 141) weeks. RESULTS: Only 6
      of 36 patients (16.7%) had tumor recurrence after mean follow-up of 67.5 weeks.
      During mitomycin instillations, only 5 patients converted from positive to
      repeated negative Quic. None of them developed tumor. Thirty-one did not convert
      and only 6 of them developed recurrent tumor. CONCLUSIONS: Quic seems not to be a
      reliable marker during mitomycin prophylaxis. After mitomycin prophylaxis, a
      repeated positive Quic, however, was associated with a high risk of recurrence
      occurring in 3 of 8 Quic-positive patients. A repeated negative or alternating
      Quic identified a lower risk group, showing 3 recurrent tumors in 28 patients
      only. We conclude that Quic cannot be used during, but after, prophylaxis to
      identify risk patients requiring further treatment. During prophylaxis, its value
      is limited to a subgroup of patients developing negative Quic, for whom
      prophylaxis can be stopped individually.

PMID- 7817482
TI  - Intravesical suramin in the prevention of transitional cell carcinoma.
AB  - OBJECTIVES: To examine the effects of intravesical suramin on N-methyl-N
      nitrosurea (MNU)-induced bladder tumors in Fischer 344 rats. METHODS: Multiple
      cohorts of female rats received four biweekly intravesical instillations of MNU.
      A control group received no other treatment, the experimental group received 25
      mg/kg intravesical suramin twice a week beginning at week 6. RESULTS: After 18
      weeks from the first instillation of MNU, 60% to 65% of control animals developed
      papillary transitional cell carcinoma, compared with only 0% to 10% of the
      suramin-treated animals (P = 0.01 to P = 0.0007). There was no local or systemic
      toxicity observed. CONCLUSIONS: Intravesical suramin is an effective
      chemopreventative therapy for transitional cell carcinoma in vivo with minimal
      toxicity.

PMID- 7817483
TI  - OA-519 (fatty acid synthase) as an independent predictor of pathologic state in
      adenocarcinoma of the prostate.
AB  - OBJECTIVES: To improve the prediction of pathologic stage beyond that provided by
      Gleason score. METHODS: We investigated the tissue expression in prostate cancer
      of a relatively new marker, oncoantigen 519 (OA-519). Because Gleason score is
      one of the most powerful predictors in prostate cancer, we restricted our
      evaluation to 66 radical prostatectomy specimens of varying pathologic stages
      which were either Gleason score 6 or 7. Immunohistochemical staining of OA-519
      was assessed with a combined staining score from 0 to 8, taking into account both
      the intensity and percentage of tissue staining. In addition, an intensity score
      was derived based on whether any intense staining was present in case. RESULTS:
      OA-519 staining of the primary prostate cancer was highly predictive in
      separating cases with organ-confined disease or capsular penetration versus cases
      with seminal vesicle invasion or lymph node metastases; Gleason score 6 or 7 was
      also predictive. In a logistic multivariate regression analysis, both OA-519 and
      Gleason score were strong independent predictors of pathologic stage (P =
      0.0004). CONCLUSIONS: OA-519 predicted pathologic stage well when analyzing
      primary prostate cancer in radical prostatectomy specimens and is presently being
      investigated on preoperative biopsy material to assess its ultimate clinical
      applicability. OA-519 has significant promise as a prognostic marker for prostate
      cancer and is one of the few markers that provides additional predictive
      information beyond that of the Gleason score.

PMID- 7817484
TI  - Transperineal palladium 103 prostate brachytherapy: analysis of morbidity and
      seed migration.
AB  - OBJECTIVES: To evaluate the early morbidity of palladium 103 (103Pd) prostate
      brachytherapy. METHODS: Thirty-two patients with Stage A or B prostate carcinoma
      were implanted transperineally with 103Pd using transrectal ultrasound and
      fluoroscopy between May 1990 and December 1992. Patients were subsequently
      followed to evaluate for morbidity and possibility of migration of the implanted
      seeds into the lungs. RESULTS: The median follow-up time was 20 months (range, 2
      to 45 months). The major acute toxicity of the procedure, dysuria, was seen in
      88% of the patients. Although this was generally grade 1 or 2 and transient,
      grade 3 or 4 toxicity occurred in 18% of patients. Mild rectal symptoms
      (transient diarrhea, rectal bleeding) occurred in 19% of patients. Sexual
      functions could not be evaluated. Seven of the 3213 total seeds implanted (0.2%)
      were found to have migrated to the lung in 6 of 30 (20%) patients having a
      postoperative chest radiograph. This did not cause any clinical problems.
      CONCLUSIONS: 103Pd prostate brachytherapy is generally associated with only mild
      or moderate urinary and rectal symptoms, and the incidence of severe
      complications is low. Further follow-up is required to evaluate the efficacy.

PMID- 7817485
TI  - Effect of age and race on the survival of men with prostate cancer in the
      Metropolitan Detroit tricounty area, 1973 to 1987.
AB  - OBJECTIVES: Reports have demonstrated that African Americans diagnosed with
      prostate cancer have a poor survival compared with whites. We examined the impact
      of age, race, and stage of disease on survival for men diagnosed with prostate
      cancer. METHODS: A retrospective analysis was made of men diagnosed with prostate
      cancer utilizing the Surveillance, Epidemiology, and End Results Program (SEER)
      database. A total of 12,907 men (9339 white, 3568 black) diagnosed from January
      1, 1973 through December 31, 1987 were included in the study. For each stage of
      disease, survival experience was examined using Kaplan-Meier and life table
      methods, followed by analysis using Cox's proportional hazard model. RESULTS:
      African-American men have a poorer survival than whites for all stages of
      prostate cancer when the cancer is diagnosed at younger ages. These differences
      in survival were not demonstrated for men diagnosed with prostate cancer after
      age 70. CONCLUSIONS: Age and race should be taken into account when assessing the
      survival of patients with prostate cancer.

PMID- 7817486
TI  - Pathogenesis and treatment of canine rhinitis.
AB  - Unless a systematic approach is used, evaluation of a patient with rhinitis can
      be frustrating to the veterinary practitioner. A complete differential list for
      canine rhinitis should include infectious, inflammatory, neoplastic, and
      traumatic causes. Other causes of rhinitis include dental disease, parasitic
      infestation, and ciliary dyskinesia. Diagnostic techniques that should be
      considered when evaluating a patient with rhinitis include obtaining a complete
      history, performing a thorough physical and oral examination, evaluating the
      patient's coagulation abilities, cytology and culture of exudate, nasal
      radiographs, and rhinoscopy. This article describes the pathogenesis and
      treatment of the various causes of canine rhinitis.

PMID- 7817487
TI  - Pathogenesis and treatment of feline rhinitis.
AB  - Diagnosis and treatment of feline rhinitis, like canine rhinitis, can be a
      frustrating experience for the veterinary practitioner. Having sound knowledge of
      the possible etiologies involved and using a systematic diagnostic approach makes
      the workup of these challenging cases much easier. Selection of appropriate
      therapy based on a definitive diagnosis makes treatment rewarding. This article
      discusses the pathogenesis and treatment of a variety of causes of feline
      rhinitis.

PMID- 7817488
TI  - Pharyngeal disorders.
AB  - Pharyngeal disorders are diverse and can include developmental, traumatic, immune
      mediated, infectious, metabolic, endocrine, neurologic, neoplastic, and
      inflammatory etiologies. Although the clinical history and signalment frequently
      can localize a disease process to the pharynx, only a careful examination,
      usually in conjunction with diagnostic tests, can identify the problem.
      Pharyngeal disorders are of important diagnostic significance. If left untreated,
      life-threatening respiratory impairment or debilitation and malnutrition may
      result. For effective treatment, therapy must be aimed at the primary disease
      process.

PMID- 7817489
TI  - Diagnosis and management of laryngeal disease in the dog and cat.
AB  - The larynx of the dog and cat controls the air flow to the lungs and prevents
      food or fluid from entering the airway during swallowing. Also, the larynx is
      important for vocalization and generating the explosive force necessary to expel
      material from the airways during the cough reflex. This article discusses the
      diagnosis and management of laryngeal disease in the dog and cat.

PMID- 7817490
TI  - Tracheostomies in the management of canine and feline upper respiratory disease.
AB  - Permanent tracheostomy and tube tracheostomy are both important for patients'
      supportive care; neither procedure cures any particular disease. Permanent
      tracheostomy is indicated to by-pass upper airway obstructions in the ambulatory
      patient needing an alternate airflow route for a long period. Temporary or tube
      tracheostomy is indicated to facilitate anesthetic management during head and
      neck surgery, long-term mechanical ventilation, and emergency patient care.
      Perioperative problems are expected with both procedures. Obstruction of the tube
      or stoma is the most common life-threatening problem. Most problems can be
      circumvented with careful and diligent patient management.

PMID- 7817491
TI  - Diseases of the nasal planum.
AB  - The most common clinical sign for owners to seek veterinary care in reference to
      the nasal planum is depigmentation in dogs and ulceration in cats. Proliferative
      (nodular) diseases are less common in dogs than in cats, because cats are more
      prone to develop squamous cell carcinoma of the nasal planum. Because a wide
      variety of diseases may present with similar clinical signs, the most helpful
      diagnostic test (after a thorough history and physical examination) is a skin
      biopsy. Discoid lupus erythematosus is the most common disease affecting the
      nasal planum of dogs in the author's practice.

PMID- 7817493
TI  - Diseases of the ear canal.
AB  - Otitis externa can be a complicated and difficult disease to diagnose and treat.
      Because of the unique physiology of the ear canal and common pathophysiology of
      otitis externa regardless of the underlying cause, the clinician must rely on
      history, dermatologic examination, and ancillary tests to determine the cause and
      appropriate therapy for a particular case.

PMID- 7817492
TI  - Pinnal diseases.
AB  - The pinna is the most obvious part of the canine and feline ear. It is a region
      of the body prone to numerous skin diseases, most of which have lesions on other
      body areas. A small number of diseases have lesions that are usually limited to
      the pinna. Other diseases involve the pinna as an initial or common site of
      disease.

PMID- 7817494
TI  - Management of otitis externa.
AB  - Otitis externa represents one of the most common reasons that pets are presented
      for veterinary attention. They are also some of the more frustrating entities
      practitioners are called on to deal with. Successful management depends on an
      understanding of the primary, predisposing, and perpetuating factors involved in
      the pathogenesis of otitis externa. Emphasis is then placed on establishing a
      diagnosis through physical examination, cytologic examination, culture and
      sensitivity testing, radiographs and biopsies. The general goals of management
      are to resolve, remove, or control primary factors, clean and dry the ear, reduce
      inflammation and resolve secondary infections. These goals are achieved through
      various cleaning techniques, topical, and systemic therapies. Therapeutic
      alternatives are given for otitis involving bacteria, Malassezia, otodectes,
      demodex, allergies, ceruminous disorders, the idiopathic
      inflammatory/hyperplastic otitis externa of cocker spaniels, "Swimmer's Ear",
      contact/irritant reactions, overtreatment, and concurrent otitis media.

PMID- 7817495
TI  - Surgery of the ear.
AB  - This article focuses on clinically relevant conditions requiring surgery of the
      ear. Indications and contraindications for various surgeries are discussed.
      Surgical procedures are detailed and postoperative care and complications are
      described.

PMID- 7817496
TI  - Ototoxicity.
AB  - This article describes the pathophysiology of ototoxic agents and contains a list
      of potential ototoxic agents including a list of animal species in which the
      toxicity has been documented or research studies performed.

PMID- 7817497
TI  - Deafness in the dog and cat.
AB  - Deafness in dogs and cats can be divided into two major categories: (1)
      conduction deafness and (2) sensorineural deafness. History and otic examination
      will often provide a diagnosis. Electrodiagnostic testing will confirm the
      deafness and further elucidate the specific cause. Therapy depends on the cause
      of the deafness and extent of involvement.

PMID- 7817498
TI  - Growth and development of follicles in different phases of the oestrous cycle in
      cows in relation to the presence of the corpus luteum and an oestrogen-dominant
      follicle.
AB  - In this work recruition and growth of follicles and quality of the largest ones
      were determined and compared in the individual stages of the bovine oestrous
      cycle (stages I, II, III and IV - days 1-4, 5-10, 11-17 and 18-21, respectively)
      in relation to the presence of the corpus luteum and an oestrogen-dominant
      follicle on the ovary. The maximum proportions of small (< 4.9 mm), medium-sized
      (5.0-9.9 mm) and large (> 10 mm) follicles were observed in stages IV (93.4%), I
      (16.6%) and III (4.8%), respectively. The results of our study revealed the
      presence of the large oestrogen-dominant follicle that have negative effects upon
      the presence of another large follicle on the ovary and upon the recruition of
      small (< 4.9 mm) follicles. On the contrary, the presence of a large oestrogen
      dominant follicle positively influenced the occurrence of 5-9.9 mm follicles in
      all stages of the cycle. No effects of the CL were observed upon the presence of
      medium-sized and large follicles. Although the differences were insignificant,
      negative effects of the CL were observed in relation to the occurrence of small
      (< 4.9 mm) follicles.

PMID- 7817499
TI  - [Improving the laboratory diagnosis of rabies and titration of rabies viruses].
AB  - For primary isolation and titration of street strains of the rabies virus from
      brains of suspected animals, an assay prepared on the cell culture BHK-21/C 13
      (rabies infection test - RTCIT) was used. The above assay proved to be reliable
      and its sensitivity proved to be comparable to the standard mouse inoculation
      test. Through this test, the results were obtained within 24 to 48 hrs on Lab-Tek
      tissue culture chamber/slides. It was found out that DEAE-dextran added to the
      cell culture only slightly increased the invasiveness of the virus in the samples
      tested. The method described herein is able to substitute the mouse inoculation
      test (MIT). In our laboratory, 20 vaccination strains of the rabies virus Vnukovo
      32/107 and 25 street strains of the rabies virus (delivered from the field) -
      original fox brain suspensions. And 10 brain suspensions were negative when
      tested in laboratory conditions (by PMIF, RTCIT as well as by MIT methods).

PMID- 7817500
TI  - [Study of the efficacy of sewage treatment systems for fluid waste on pig farms
      in Slovakia].
AB  - Bacteriological, helminthological and physico-chemical examinations were carried
      out to investigate the technological procedure in three water treatment plants
      treating slurry from large-capacity pig farms (Kosicka Polianka, Spisske Vlachy,
      Vel'ky Dur). Our investigations were focused on the testing of effectiveness of
      mechanical, chemical and biological treatment system most frequently used in
      Slovakia. Our investigations revealed that water-treatment plants, operating on
      pig farms, fulfil only the supplies management requirements concerning the
      treated water, discharged into the recipient. From the hygienic viewpoint further
      processing or utilization of the solid fraction remains unsolved. This fraction
      contains considerable concentrations of bacteria and parasitic germs (Ascaris
      suum, Trichuris suis, Isospora sp., Eimeria sp.) most of which exhibit high
      tenacity in the environment. It is recommended to process this solid fraction by
      composting before it is applied as a manure. However, the measured values did not
      exceed the reference hygienic limits. The technological stage of chemical
      treatment, which follows after the separation and utilizes some coagulants
      (aluminium sulphate, ferrous sulphate), can increase the chemical load of water
      stripped of crude organic pollutants, by some undesirable chemical elements.

PMID- 7817501
TI  - [Development of PCR tests for the detection of bovine herpesvirus-1, bovine
      respiratory syncytial viruses and pestiviruses].
AB  - The development of PCR assays for detection of BHV-1, BRSV, BVDV and another
      pestiviruses is summarized. A polymerase chain reaction assay based on primers
      selected from the viral gI glycoprotein gene detected 3 fg pure BHV-1 DNA, 0.1
      1.0 TCID50 or a single infected cell. No amplification was observed with DNA from
      BHV-2, BHV-3, BHV-4, OHV-1 or OHV-2. However, a fragment of the correct size (468
      bp) was amplified using DNA from herpesviruses isolated from reindeer, red deer
      and goat. The PCR assay was able to detect virus in nasal swabs 1-14 days after
      experimental infection of cattle and there was a good correlation when PCR was
      compared to virus isolation for the detection of BHV-1 in clinical field samples.
      Detection of BHV-1 in fetal bovine serum and semen samples was also successful.
      PCR detecting a broad range of BVDV, BDV and HCV was developed. Of six sets of
      primers selected from different parts of the pestivirus genome the best results
      were provided by a pair 324/326 from the highly conserved 5'-non-coding region
      which gave an amplification with all 129 isolates tested. This panel consisted of
      79 isolates from cattle, 33 from pigs and 17 from sheep. Differentiation between
      viruses was achieved by cleavage of the PCR-amplified products (288 bp) with the
      restriction endonucleases AvaI and BglI. The BVDV products were cleaved by AvaI,
      HCV by BglI and AvaI. Both enzymes, AvaI and BglI, did not cut the BDV products.
      A nested polymerase chain reaction assay was developed for the detection of
      bovine respiratory syncytial virus (BRSV). Primers were selected from the gene
      encoding the F fusion protein. The sensitivity of PCR assay was 0.1 TCID50. No
      cross reaction was observed with nine heterologous respiratory viruses. PCR
      products of bovine and human RSV strains were discriminated using endonuclease
      ScaI, which specifically cleaved products of BRSV. PCR assay detected BRSV in
      nasal swabs collected from cattle in the acute stage of respiratory disease. In
      vitro amplification detected 31 positive samples of 35 while immunofluorescence
      only 23 samples.

PMID- 7817503
TI  - Animal welfare first.

PMID- 7817502
TI  - [Colonization of the digestive tract by defined lactoflora in gnotobiotic and
      conventional lambs].
AB  - The effect of Lactobacillus casei 249/89 on the colonization of the intestinal
      tract and selected indicators of the metabolic profile of gnotobiotic and
      conventional lambs from the viewpoint of its possible utilization in the
      prevention of diarrhoeal syndrome of bacterial etiology in young animals has been
      studied. Five gnotobiotic and three conventional lambs were used in these
      studies. The lambs were slaughtered at 3, 6, 10, 15 and 21 days of age. The
      population of L. casei colonizing the intestinal epithelium was at the age
      dynamics on average higher in gnotobiotic lambs compared with lactobacilli in
      conventional lambs (Fig. 1). The significant difference (p < 0.001) was noted at
      the age of 3 days (gnotobiotic lambs = 3.40 log 10/cm2 and conventional lambs =
      1.08 log 10/cm2). Also the counts of lactobacilli colonizing individual sections
      of the intestine (Fig. 2) was on average higher in gnotobiots with significant
      differences in jejunum and colon (p < 0.05). In both groups, the highest number
      of lactobacilli was observed on the intestinal epithelium in lower sections of
      the digestive tract. In gnotobiots, the population of L. casei colonizing the
      duodenum was highest at the age of 3 days (3.49 log 10/cm2), in jejunum (3.74 log
      10/cm2) and in ileum 4.37 log 10/cm2) at the age of 6 days and in the colon (4.7
      log 10/cm2) at the age of 15 days (Fig. 3). In conventional lambs, the population
      of lactobacilli colonizing individual sections of the intestinum was increasing
      with age (Fig. 4). The number of L. casei in the intestinal content of
      gnotobiotic lambs was on average higher than that in conventional animals but the
      differences were not significant. In both groups, the highest number of
      lactobacilli was noted at the age of 10 days (gnotobiotic lambs = 5.9 log 10/ml;
      the conventional lambs = 4.6 log 10/ml). From the viewpoint of individual
      sections of the intestine, the population of L. casei in the intestinal content
      of gnotobiotic lambs was higher than the lactobacilli count in conventional
      animals with significant difference in jejunum (p < 0.01). In gnotobiots, the
      highest lactobacilli count was in the colon (6.17 log 10/ml); in conventional
      lambs in the ileum (4.71 log 10/ml).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7817504
TI  - Vaccination of commercial layer chicks against infectious bursal disease with
      maternally derived antibodies.
AB  - Day-old commercial layer chicks with maternally derived antibody to infectious
      bursal disease (IBD) were reared in four pens on a commercial farm, and chicks
      from the same flock were reared at the laboratory and examined for the decay of
      the maternal antibody and the development of susceptibility to IBD. The chicks in
      the pens on the farm were vaccinated with different combinations of commercial
      inactivated and live vaccines against IBD, transferred to the laboratory, and
      challenged with virulent IBD virus to assess the efficacy of the vaccination
      programmes. The chicks from one pen, given a live IBD vaccine only, did not
      develop antibodies and were fully susceptible to challenge by seven weeks old;
      only one to two weeks later than the unvaccinated control chicks reared at the
      laboratory. The chicks in the other three pens were inoculated with an
      inactivated vaccine, and the chicks in two of these pens were inoculated later
      with a live vaccine. All these chicks developed IBD antibodies and were protected
      by between 91 and 100 per cent against challenge. There was no demonstrable
      benefit in administering a live vaccine either alone or in addition to an
      inactivated oil emulsion vaccine.

PMID- 7817505
TI  - Rapid diagnosis of equine influenza by the Directigen FLU-A enzyme immunoassay.
AB  - The Directigen FLU-A enzyme immunoassay was tested for its ability to detect
      equine-2 influenza viruses in nasopharyngeal fluids from horses and ponies. A
      total of 125 swabs from experimental infections and from different sources of
      natural infection in the USA and Hong Kong were examined. The assay results were
      compared with the results of standard virus culture in embryonated chicken eggs
      or Madin-Darby canine kidney cells, and with the serology of the horses sampled.
      In comparison with virus culture the enzyme immunoassay exhibited 83 per cent
      sensitivity, 78 per cent specificity, 70 per cent positive predictive value and
      88 per cent negative predictive value. The test appeared to be more sensitive
      than haemagglutination for the detection of low levels of virus in embryonated
      egg cultures. It also detected equine-1 influenza virus in culture. The test is
      rapid (15 minutes), simple, and should be a convenient method for the rapid
      diagnosis and screening of horses for equine influenza infection.

PMID- 7817506
TI  - An outbreak of enterotoxaemia caused by Clostridium perfringens type D in goats
      in Patagonia.
AB  - Forty-four of a flock of 117 angora goats in the Rio Negro province of Argentina
      died within four days. Most of the animals died shortly after the onset of
      clinical signs, but in a few the clinical course lasted for several days. Post
      mortem the small and large intestines were filled with watery contents, blood and
      fibrin clots, and there were numerous ulcers on the mucosa. Small areas of
      malacia were observed histologically in the brain. Clostridium perfringens type D
      in pure culture was isolated from the kidneys and gut contents of the affected
      animals. Epsilon toxin was identified by the mouse seroneutralisation test in the
      supernatant solution from cultures of these isolates and in the intestinal
      contents of the affected animals. Heavy infestations with coccidia, nutritional
      and environmental stress, and an anthelmintic overdose were possible predisposing
      factors for the outbreak.

PMID- 7817507
TI  - Macrothrombocytosis in cavalier King Charles spaniels.
AB  - Low platelet counts (< 150 x 10(9)/litre) have been measured by autoanalyser in
      cavalier King Charles spaniels with a wide range of diseases. However, the direct
      examination of blood smears revealed adequate numbers of platelets but many
      abnormally large platelets and it was not clear whether the large platelets were
      the result of disease or a breed abnormality. The numbers and diameters of the
      platelets in a group of clinically normal King Charles spaniels and a group of
      other breeds were measured by autoanalyser and manually. The automated platelet
      counts were lower in the King Charles spaniels than in the other breeds (P <
      0.01), but the manual counts were similar. The platelet diameter was greater in
      the cavalier King Charles spaniels (median values 2.5 to 3.75 microns, P < 0.001)
      than the other breeds (median values 1.25 to 2.5 microns) and had a bimodal
      distribution with peaks at 1.25 to 2.5 microns and 3.75 to 5 microns. No clinical
      evidence of platelet dysfunction was detected. These findings indicate that
      cavalier King Charles spaniels may have large platelets which could lead to the
      erroneous diagnosis of thrombocytopenia by automated haematological analysis.

PMID- 7817508
TI  - Borna virus infections in cattle associated with fatal neurological disease.

PMID- 7817509
TI  - Pneumonia in Moorish tortoises (Testudo graeca) associated with avian serovar A
      Chlamydia psittaci.

PMID- 7817511
TI  - Ravages of rinderpest.

PMID- 7817510
TI  - Cholesterinic granulomas in horses.

PMID- 7817512
TI  - VHS confirmed on Scottish island.

PMID- 7817513
TI  - International disease surveillance: April to June 1994.

PMID- 7817514
TI  - Epidemiological observations on spongiform encephalopathies in captive wild
      animals in the British Isles.
AB  - Since 1986, scrapie-like spongiform encephalopathy has been diagnosed in 19
      captive wild animals of eight species at or from eight zoological collections in
      the British Isles. The affected animals have comprised members of the family
      Bovidae: one nyala (Tragelaphus angasi), four eland (Taurotragus oryx), and six
      greater kudu (Tragelaphus strepsiceros), one gemsbok (Oryx gazella), one Arabian
      oryx (Oryx leucoryx), and one scimitar-horned oryx (Oryx dammah), and members of
      the family Felidae: four cheetah (Acinonyx jubatus) and one puma (Felis
      concolor). In addition, three cases of a spongiform encephalopathy of unknown
      aetiology have been reported in ostriches (Struthio camellus) from two zoos in
      north west Germany. Three features suggest that some of these cases may have been
      caused by the agent of bovine spongiform encephalopathy (BSE). First, they have
      been temporally and geographically coincident with the BSE epidemic. Secondly, in
      all the ungulates for which details are available, it is possible that either the
      affected animal itself, or the herd into which it was born or moved, had been
      exposed to proprietary feeds containing ruminant-derived protein or other
      potentially contaminated material, and all the carnivores had been fed parts of
      cattle carcases judged unfit for human consumption. Thirdly, the pathological
      results of inoculating mice with a homogenate of fixed brain tissue from the
      nyala and from one greater kudu were similar to the results of inoculating mice
      with BSE brain tissue.

PMID- 7817515
TI  - Development of early bovine embryos in different culture systems.
AB  - The objective of this study was to examine the effects of different culture
      systems on the development of early bovine embryos in vitro. A total of 1089
      oocytes were aspirated from 2 to 5 mm follicles of ovaries collected at a local
      abattoir; a high proportion of the oocytes matured in vitro were fertilised by
      spermatozoa capacitated with caffeine and heparin. Seven to eight hours after
      insemination, the oocytes were transferred into three in vitro systems: A, TCM
      199 + 10 per cent fetal calf serum culture medium, B, coculture with a monolayer
      of granulosa cells and C, coculture with bovine oviductal epithelial cells. The
      results showed that the proportion of the early bovine embryos which overcame the
      block at eight to 16 cells and developed to the morula and blastocyst stages in
      system C was significantly higher than in systems A or B.

PMID- 7817516
TI  - Use of intraocular adrenaline during cataract extractions in dogs.

PMID- 7817517
TI  - Isolation of an ivermectin-resistant strain of Haemonchus contortus from sheep in
      Malaysia.

PMID- 7817519
TI  - Submissions to the BVA/KC hip dysplasia scheme.

PMID- 7817518
TI  - Isolation and identification of Mycoplasma mycoides subspecies mycoides SC from
      bull semen and sheath washings in Portugal.

PMID- 7817520
TI  - Uraemia in cases of cryptosporidiosis.

PMID- 7817522
TI  - [Effects of the degree of fish oil oxidation on the state of xenobiotic
      metabolism enzymes].
AB  - Wistar male rats received polysynthetic diets incorporating lard or fish of
      different oxidation degree as the sourse of fat. The feeding lasted 4 weeks. In
      the liver of rats on fish oil diet the activity of the enzymes of xenobiotic
      metabolism phase I (monooxigenase system, epoxide hydrolase, carboxyl esterase)
      and phase II (native and activated UDP-glucuronosyl transferase, glutathione
      transferase) located both in microsoma membranes and in cytozole was higher than
      in the animals on lard diet. The enzyme activity was much more enhanced in the
      use of oxidated fish oil. No effect of fish oil on serum and lysosome enzyme
      activity and rat hepatic structure was found.

PMID- 7817521
TI  - [Possibilities of correcting atherogenic trends of the diet in l4-15-year-old
      boys].
AB  - In a representative sample of boys aged 14-15 daily diet compositions have been
      modeled followed by 2-year preventive correction of expected atherogenic shifts
      in the above boys' nutrition. The correction did not imply changes in daily diet
      overall caloric value, but the intake of refined sugar was to be reduced with an
      increase in the intake of other carbohydrates and decrease in saturated fatty
      acids. The proportion of polyunsaturated fatty acids in daily diets was made
      greater. The highest effect was achieved in the boys who had not only changed
      their diet qualitatively, but also made their meals more frequent that is adopted
      dietary regimen with meals 3-4 times a day.

PMID- 7817524
TI  - [Antibiotics in food products: new aspects of the problem].

PMID- 7817523
TI  - [Effects of the intake of free amino acids on permeability of the protective
      intestinal barrier to macromolecules in normal state and in sensitization].

PMID- 7817525
TI  - [Detection of enterotoxigenic staphylococci in milk and cheese].
AB  - The enzyme immunoassay examinations of 123 milk and cheese samples for
      enterotoxigenic staphylococci have revealed contamination of raw milk with
      coagulase-positive staphylococci producing A and B enterotoxins. "Rossiysky"
      cheese samples were also contaminated with S. aureus producing enterotoxins. The
      capacity to produce enterotoxins was found in 19.6% (21 strains) of 107
      identified strains.

PMID- 7817526
TI  - [Selenium intake of inhabitants of the Bryansk region living in radioactive
      contamination areas].
AB  - Selenium content in foodstuffs of Briansk region is investigated. The mean level
      of selenium consumption is shown to be 54,0 pg/day. Import of foodstuffs with low
      selenium concentration to Briansk region situated at selenium-deficient soils is
      emphasized.

PMID- 7817527
TI  - [Effects of selenium on endogenous synthesis of N-nitrosamines and toxicity of
      nitrites in rats].
AB  - Male Wistar rats were fed selenium (0.2, 2.9 or 5.5 mg/kg of dry feed) in the
      form of selenomethionine. They also received for 6 weeks amidopyrine (33 mg/kg
      b.w.) and/or sodium nitrite (20 mg/kg b.w.) administered intragastrically. The
      quantitation of endogenously synthetized volatile nitrosamines in the stomach,
      selenium in the serum, biochemically evaluated nitrite and nitrosamines toxicity
      revealed an inverse relationship between feed selenium concentrations and the
      amount of endogenously produced nitrosodimethylamine from equal precursor doses.
      A protective selenium effect on methemoglobin-producing action of nitrite ions
      was established. It is shown that introduction of precursors induces increased
      body need in selenium.

PMID- 7817528
TI  - [Effectiveness of increased contents of dietary fiber in early stages of non
      insulin-dependent diabetes mellitus].
AB  - Patients with early NIDDM were put on routine diet N 9 (food fiber 25 g/day) and
      test diet (food fiber 55 g/day). The diet of both groups (group 1 and 2,
      respectively) was supplemented with oral mineral water Essentuki 17. High-fiber
      diets proved to be effective for the above patients as they induced positive
      trends in NIDDM clinical symptoms, body weight, lowering of basal insulin, an
      increase in insulin immediate pool. There was also a reduction of insulinemia and
      hyperglycemia later in the course of glucose tolerance test. The above shifts
      were more pronounced in 2 patients.

PMID- 7817529
TI  - [Therapeutic-prophylactic food prepared from Cucumaria].

PMID- 7817530
TI  - [Dietary effects of PUFA omega-3 on lipid peroxidation and antioxidant system in
      patients with IHD, hyperlipoproteinemia and hypertension].
AB  - Dietary effects of polyunsaturated fatty acids (PUFA) omega-3 on lipid
      peroxidation (LPO) and antioxidant system were studied in 73 patients with
      ischemic heart disease, hyperlipoproteinemia (HLPE) type IIa, IIb, IV and
      essential hypertension. Eiconol-enriched antiatherosclerotic diet has more potent
      hypolipidemic, hypotensive and thrombolytic action in association with inhibition
      of LPO, enhances SOD activity, keeps red cell catalase within normal. Vitamin E
      concentrations were not changed. It is suggested that eiconol addition to
      antiatherosclerotic diet causes no LPO induction and is pathognomonic for HLPE,
      hypertension and IHD patients.

PMID- 7817531
TI  - [Improved device and method for determination of protein digestibility in vitro].
AB  - The ten-cells device for modelling of ferment hydrolysis of food proteins by acid
      basic proteases of human alimentary canal is described. The new procedure for the
      calculation of quantitative characteristic of proteins digestion "in vitro" is
      presented.

PMID- 7817532
TI  - [X-ray phase method of determining microcrystalline cellulose in bakery
      products].

PMID- 7817533
TI  - [Diet therapy in chronic pancreatitis].

PMID- 7817534
TI  - [Dynamics of several parameters of microelement metabolism, vitamin C intake and
      physical work capacity of forge workers during the course of the year].
AB  - Measurements of minerals and vitamins in forge workers throughout the year
      revealed that in autumn and winter blood levels of iron, hemoglobin, the activity
      of peroxidase and ceruloplasmin, dietary levels of iron, copper and manganese
      were higher than in spring and summer. Iron and copper metabolism was closely
      related to total protein in the serum and vitamin provision. Muscular performance
      of the forge workers was found reduced in spring and summer and was correlated
      with iron and copper metabolism.

PMID- 7817535
TI  - Parkinsonian-like tremors in the recovery phase of kwashiorkor.
AB  - Kwashi shakes is described in a 17-month-old Jamaican male infant. This is the
      first reported case seen at the Tropical Metabolism Research Unit at the
      University of the West Indies, Mona, Jamaica and the first documented case in the
      West Indian literature.

PMID- 7817536
TI  - Spinal epidural abscess. Diagnosis and management.
AB  - Three cases of spinal epidural abscess managed at the University Hospital of the
      West Indies are presented. This disorder, a neurosurgical emergency, runs a
      variable course, and, if improperly managed, may lead to paraplegia and death.
      The aetiology, diagnosis and management of this disease are discussed.

PMID- 7817537
TI  - Aneurysm of the gluteal artery.
AB  - One case of atherosclerotic gluteal artery aneurysm (GAA) is presented. The
      diagnosis was made preoperatively, and treatment involved ligation and division
      of the internal iliac artery only. This therapeutic option is discussed as the
      preferred one compared to the conventional two-step procedure.

PMID- 7817538
TI  - Factors to be considered in devising an effective programme for the reduction of
      road traffic accidents.

PMID- 7817539
TI  - Effect of aqueous neem (Azadirachta indica) extract on testosterone and other
      blood constituents in male rats. A pilot study.
AB  - Effect of oral administration of crude aqueous neem extract on serum testosterone
      and other blood constituents was studied in the male Wistar rats for 10 weeks.
      The neem treatment resulted in significant decreases (p < 0.01) in total
      testosterone, total bilirubin and K+ in serum. There were also increases (p <
      0.05) in packed cell volume, mean corpuscular haemoglobin concentration, red
      blood cell, white blood cell and lymphocyte counts without showing any cytotoxic
      effects in the body.

PMID- 7817540
TI  - Microscopical and serological diagnosis of Wuchereria bancrofti.
AB  - Venous blood from 292 patients attending a Filaria Clinic in Georgetown, Guyana,
      was assayed by ELISA for IgG and IgM antibodies and by Indirect Haemagglutination
      Antibody Assay (IHA) against filaria parasites. They were also assayed by
      microscopic methods before and after concentration procedures for
      microfilaraemia. Of the 41 blood samples microscopically positive for Wuchereria
      bancrofti microfilariae, 87.8% (ELISA IgG), 65.9% (ELISA IgM) and 73.2% (IHA)
      occurred in samples with sub-diagnostic serological threshold titres of < 1:32
      (IgG and IgM) and < 1:128 (IHA). But indicators of value based on the standards
      of the presence of chronic and acute symptoms, the IgG and IgM diagnostic data
      gave 79.9% sensitivity, 96.4% specificity, 97.1% positive predictable value and
      44.3% negative predictive value. A membrane filtration system (92.7%) was
      slightly better than a centrifugation technique (90.2%), but more efficient than
      a thick smear preparation (75.6%) for the detection of microfilariae. The
      filtration system was vastly superior for yields of microfilariae. However, the
      Knott's concentration (sedimentation) was the most economical in terms of
      technician time and materials. Most microscopically confirmed filaria cases were
      in the 20-29-year age group (25%), followed by the broad 30-69-year age groups
      (10-12%). Males were significantly more commonly affected by the ratio 24.2:6.0.
      It is recommended that skills and materials for concentration of microfilariae
      from peripheral blood be maintained in all Caribbean countries. In known filaria
      endemic countries, it is recommended that the serological tool be used as an aid
      in diagnosis for patients with acute and chronic symptoms.

PMID- 7817541
TI  - Seroepidemiology of chlamydial infection among a sexually-active population in
      Barbados.
AB  - During a two-year period, sera from 1179 patients with urogenital tract symptoms
      and from 256 controls were tested for IgG and IgA antibodies to Chlamydia
      trachomatis, using a commercially prepared indirect immunoperoxidase assay. Of
      the patient sera, 1051 (89%) were from female patients and 128 (11%) were from
      males. Specimens were received from patients attending private practitioners
      (424), government polyclinics (348), the Queen Elizabeth Hospital (206), the
      Barbados Family Planning Association (117) and various other sources (84). Nine
      hundred and fifty-nine of specimens (81%) from all patients had IgG titres of 64
      or greater, and 441 (37%) had IgA titres of 16 or greater. A lower proportion of
      male patients (43%) than female patients (61%) had IgG titres of 128 or greater.
      Among 76 control females attending the antenatal clinic, IgG was detected in 76%
      and IgA in 16%, while among 75 adult blood donors, IgG was detected in 70% and
      IgA in 39%. A group comprising 97 asymptomatic children aged 9 months to 13
      years, and 8 adolescents aged 14-18 years was also studied. IgG antibodies (titre
      > or = 64) were detected in 13.4% of children and in 50% of the adolescents. IgA
      antibodies were detected in only 1% of children and adolescents. Antibodies were
      not detected in children under the age of 5 years. The detection of antibodies by
      indirect immunoperoxidase assay in such a high proportion of the population
      suggests that this method is of little value for diagnosis of infection with
      Chlamydia trachomatis.

PMID- 7817542
TI  - Helicobacter pylori in patients undergoing upper endoscopy in Jamaica.
AB  - One hundred and two consecutive patients undergoing upper gastrointestinal
      endoscopy were tested for H. pylori by a rapid urease test, using antral biopsy
      specimens. There were 60 men (mean age 54 yrs) and 42 women (mean age 49 yrs).
      Fifty-six patients (55%) were positive for H. pylori. Of male patients, 36 (60%)
      and of female patients, 20 (48%) tested positive. Sixty-eight per cent of
      patients with antral gastritis, 65% with duodenal ulcer and 60% with gastric
      ulcer had H. pylori. Thirty-nine patients (70%) positive for H. pylori were from
      major urban areas, and 17 (30%) were from rural areas of Jamaica. In patients
      without H. pylori, 61% and 39% were from urban and rural areas, respectively.
      Forty-four patients (79%) with H. pylori and 40 (87%) without H. pylori had piped
      water in their homes. Ninety-three per cent of all patients had electricity and
      88% had refrigeration. There was no difference between patients positive or
      negative for H. pylori with regard to the use of alcohol, marijuana or tobacco.
      There was also no difference between both groups in exposure to domestic animals
      in the home environment. H. pylori is associated with antral gastritis and peptic
      ulcer disease in Jamaican patients. There are no specific environmental or social
      factors that seem to predispose to infection.

PMID- 7817543
TI  - The intestinal permeability test applied to the diagnosis of food allergy in
      paediatrics.
AB  - Intestinal permeability was evaluated in 17 healthy young children (control
      group), aged 4.3 +/- 1.9 years (mean +/- SD), weight 15.4 +/- 5.5 kg and in 11
      infants with food allergy (allergic group, aged 2.3 +/- 1.6 years, weight 9.5 +/-
      1.5 kg). In the two groups, the urinary excretion of two non-metabolized sugars
      (mannitol, lactulose) was measured by gas-chromatography after oral
      administration. Measurement of urinary content of these sugars 5 hours after
      administration in the control group showed a clearance of 20.2 +/- 8.6% for
      mannitol and 0.44 +/- 0.18% for lactulose. The lactulose/mannitol ratio in the
      same group was equal to 0.023 +/- 0.008. When compared to the control group, the
      11 patients of the allergic group presented a normal mannitol urinary excretion
      (16.5 +/- 13.4%, p = NS, Student's t-test) and an increase in the lactulose
      excretion (1.36 +/- 0.92%, p < 0.001). Moreover, the allergic group showed a
      lactulose/mannitol ratio that was significantly different (0.105 +/- 0.071, p <
      0.001). The intestinal permeability test for the diagnosis of food allergies
      seems to be a sensitive and non-invasive test that is well suited to the
      paediatric practice.

PMID- 7817544
TI  - Prognosis of neuroblastic tumours in children.
AB  - A retrospective analysis of 26 children with neuroblastic tumours treated at the
      University Hospital of the West Indies (UHWI) between 1970 and 1991 was
      undertaken to evaluate factors affecting prognosis. The peak incidence was
      between 48 months and 60 months of age, and 75% of the deaths occurred in
      children older than 3 years. The abdomen was the most common site of the tumours
      79% of which were from the adrenal gland and carried a dismal outcome. Other
      sites were thoracic, pelvic and cervical. Extra-adrenal tumours have a good
      outcome even when the histology is unfavourable; 92% of the tumours were in
      Stages III or IV at the time of initial presentation. Stage IV disease accounted
      for all but one of the deaths. Of the 8 children with favourable histology
      (ganglioneuroma or well-differentiated ganglioneuroblastoma), only one (12.5%)
      died, wheras of the remaining 18 cases with unfavourable histology (neuroblastoma
      and undifferentiated ganglioneuroblastoma), eleven (61.1%) died. When managed by
      surgery alone or with adjuvant chemo- and/or radio-therapy, only 36.4% succumbed
      while all 4 children with chemotherapy only died. Ten children are alive without
      disease for more than three years post-therapy. A scoring system was designed
      which takes into account the factors influencing the outcome in neuroblastic
      tumours, namely, age, location, stage and histological types of the tumours and
      therapy. All the children with a score of 21 or less survived, whereas all those
      with scores of 22 or above succumbed. This underlines the multifactorial
      influences on the final outcome of neuroblastic tumours.

PMID- 7817545
TI  - Unintended and unwanted pregnancy in St. Lucia.
AB  - Among 200 mothers interviewed in St. Lucia, 82.5% described their pregnancy as
      unintended and 44% as unwanted; 80% of women having an intended pregnancy and
      94.6% having an unintended pregnancy were unmarried and 18.5% were teenagers.
      Mothers of unintended pregnancies were significantly younger, were of
      significantly higher parity and had begun sexual relations at a significantly
      earlier age than mothers of intended pregnancies; and, unlike mothers of planned
      pregnancies, their desired interpregnancy interval was significantly longer than
      the actual interval. These results and the sporadic and ineffective use of
      contraception in St. Lucia emphasize the need for improvements in fertility
      regulation in that country.

PMID- 7817546
TI  - Health status of shut-ins in the Marigot Health District, Commonwealth of
      Dominica.
AB  - In the Commonwealth of Dominica, the health and disability status of 108 people
      who, for various reasons, are confined to their homes--the so-called "shut-ins"-
      were studied. Eighty per cent of them were over 65 years of age and 10% were
      children. Most shut-ins were independent in self-care but dependent in general
      activities. Their overall health was poor. Twenty-one suffered from diseases of
      the musculo-skeletal system c.q. osteoarthritis, 13 from blindness of various
      origins, 13 from neurological diseases, 13 from CVA, psychosis or dementia and 13
      from different other diseases. One-third suffered from more than one disease. A
      special programme would be required to optimize the home-care for the shut-ins
      and to encourage them to become more active.

PMID- 7817547
TI  - Does fear of immigration authorities deter tuberculosis patients from seeking
      care?
AB  - Physician groups are concerned that legislation requiring physicians to report
      illegal immigrants to immigration authorities will delay curative care. In
      particular, patients with tuberculosis may delay seeking care for infectious
      symptoms and spread the disease. We surveyed 313 consecutive patients with active
      tuberculosis from 95 different facilities to examine the relationship of
      immigration-related variables, symptoms, and delay in seeking care. Most patients
      (71%) sought care for symptoms rather than as a result of the efforts of public
      health personnel to screen high-risk groups or to trace contacts of infectious
      persons. At least 20% of respondents lacked legal documents allowing them to
      reside in the United States. Few (6%) feared that going to a physician might lead
      to trouble with immigration authorities. Those who did were almost 4 times as
      likely to delay seeking care for more than 2 months, a period of time likely to
      result in disease transmission. Patients potentially exposed an average of 10
      domestic and workplace contacts during the course of the delay. Any legislation
      that increases undocumented immigrants' fear that health care professionals will
      report them to immigration authorities may exacerbate the current tuberculosis
      epidemic.

PMID- 7817548
TI  - Fecal occult blood testing for colorectal cancer in an ethnically diverse
      population.
AB  - Fecal occult blood test kits were distributed throughout the ethnically diverse
      Hawaiian Islands during a 3-week period in 1989. Occult blood was detected in
      1,631 persons (11.8%). At least 83% of the participants with positive tests
      sought medical advice. Subsequently, 76 (4.7%) were diagnosed as having
      colorectal adenomas and an additional 1.4% had malignant neoplasms (3 gastric and
      20 colorectal adenocarcinomas). Three quarters of the colorectal cancers were
      localized and node-negative. Participation in this program and the type of
      diagnostic studies done on participants with positive tests varied according to
      sex and ethnicity. Therefore, these demographic variables must be considered in
      designing fecal occult blood screening programs.

PMID- 7817549
TI  - Community-acquired pneumonia in adults.
AB  - Although the frequency of community-acquired pneumonia caused by Streptococcus
      pneumoniae continues to be high, studies show that Mycoplasma pneumoniae,
      Chlamydia pneumoniae, or Legionella pneumophila are the etiologic agents in 20%
      to 40% of community-acquired pneumonia in adults. The clinical presentation of
      pneumonia caused by these organisms may be indistinguishable from pneumonia due
      to S pneumoniae. Separation of cases of pneumonia due to S pneumoniae as typical
      and that caused by M pneumoniae, C pneumoniae, or L pneumophila as atypical is
      unwarranted and unhelpful in planning therapy. As many as 35% to 50% of patients
      do not have an etiologic agent identified. Community-acquired pneumonia can have
      high morbidity and mortality in patients who are older, have underlying lung
      disease, diabetes mellitus, or other comorbid conditions, or who have decreased
      immune function regardless of the specific etiologic agent. In choosing
      appropriate empiric antimicrobial therapy in hosts who are not immunocompromised,
      erythromycin and other macrolide antibiotics have the advantage of being
      effective against a wide range of pathogens likely to be encountered, including S
      pneumoniae, M pneumoniae, and L pneumophila, and of having some benefit against C
      pneumoniae. In other patients, the selection of antibiotic therapy can be based
      on age, clinical suspicion, epidemiologic data, and laboratory test results.
      Antimicrobial therapy can be directed at specific organisms when and if they are
      identified.

PMID- 7817550
TI  - 'Pals'. A medical student public service program.
AB  - We designed a public service and educational program to aid children and families
      coping with chronic illness and to augment medical student education. Medical
      students developed relationships with chronically ill children and families based
      on the Big Brother-Big Sister program model. In addition, students attended
      bimonthly seminars on childhood chronic illness and family dynamics. Medical
      students learned about the psychosocial aspects of illness through these
      relationships and reported that the program contributed to their sense of worth
      as caregivers. By fostering students' innate altruism, medical schools may
      succeed in cultivating caring and humanism in their student physicians. We
      propose a model that encourages medical students to relate personally with
      patients and their families. A program such as this has the potential to nurture
      compassion in medical students, contribute to medical education, and provide
      support to patients and families.

PMID- 7817552
TI  - Bone imaging using single-photon emission computed tomography.

PMID- 7817553
TI  - New diagnostic tests combining drugs and nuclear medicine.

PMID- 7817551
TI  - Paradoxes of body fluid volume regulation in health and disease. A unifying
      hypothesis.
AB  - The body's normal homeostasis is maintained by the integrity of the excretory
      capacity of the kidneys. In advanced cardiac failure, however, the avidity of the
      renal sodium and water retention contributes to the occurrence of pulmonary
      congestion and peripheral edema. In patients with advanced cirrhosis, the kidneys
      again fail to excrete the amounts of sodium and water ingested, thus leading to
      ascites and peripheral edema. The signals for this renal retention of sodium and
      water in a patient with cirrhosis must be extrarenal because when the same
      kidneys are transplanted into persons with normal liver function, renal sodium
      and water retention no longer occurs; rather, the kidneys maintain normal fluid
      and electrolyte balance. Excessive sodium and water retention by the kidneys also
      occurs during pregnancy despite a 30% to 50% increase in plasma volume, cardiac
      output, and glomerular filtration rate. What are the afferent and efferent
      signals whereby normal kidneys retain sodium and water so that total
      extracellular, interstitial, and intravascular volumes expand far beyond those
      limits observed in normal subjects? These dilemmas are the subject of this
      review, in which a "unifying hypothesis of body fluid volume regulation" is
      presented.

PMID- 7817554
TI  - Positron emission tomographic oncology.

PMID- 7817555
TI  - Monoclonal antibody imaging of colorectal and ovarian cancer.

PMID- 7817556
TI  - Regional cerebral blood flow and cocaine abuse.

PMID- 7817557
TI  - Technetium Tc 99m sestamibi for parathyroid imaging.

PMID- 7817559
TI  - Lactic acidosis in a patient with multiple myeloma.

PMID- 7817558
TI  - Mycobacterium avium-intracellulare and acute abdominal pain.

PMID- 7817561
TI  - Case report 23289 and medical economics.

PMID- 7817560
TI  - Hemorrhagic fever with renal syndrome in California.

PMID- 7817562
TI  - Health care costs and technologies.

PMID- 7817564
TI  - Laparoscopic colectomy--an initial experience.

PMID- 7817563
TI  - Dilemma of high-tech care for high-risk patients.

PMID- 7817565
TI  - Recurrent hyperthermia due to lovastatin.

PMID- 7817566
TI  - Communicating with patients.

PMID- 7817567
TI  - [Characteristics of patients with pulmonary tuberculosis].
AB  - The purpose of the study was presentation of the characteristics of patients
      treated for various forms of pulmonary tuberculosis at the Chair and Department
      of Pulmonary Diseases and Tuberculosis Medical Academy in Gdansk in the years
      1977-1991. On the basis of medical documentation the incidence and age
      distribution were analysed. The proportions of patients with different forms of
      tuberculosis and the duration of their treatment were calculated. In the selected
      years 1977, 1982, 1987, 1991 the results of bacteriological investigations
      confirming the diagnosis were compared. In the light of the obtained data it was
      found that in the last 15 years there was an increase in the number of patients
      aged over 50 years. In the years 1990 and 1991 a higher per cent of cases of
      miliary tuberculosis and caseous pneumonia was found as compared with the years
      1977-1978. Caseous pneumonia was diagnosed in 8.4% of all patients treated for
      tuberculosis in 1977, while in 1991 this proportion was 14.5%. Positive results
      of bacteriological examination in 1977 were obtained in 57% of cases, in 1987 in
      58.8%, and in 1991 in 35 cases, that is 63.6% of all cases of pulmonary
      tuberculosis.

PMID- 7817568
TI  - [Effect of bilipolin and uropolin on metabolic activity of neutrophils].
AB  - In 30 patients the metabolic activity of the neutrophils measured with the
      reduction ability of nitroblue tetrazolium was determined after intravenous
      administration of iodinated contrast media for cholangiography or urography. It
      was shown that 20 minutes after intravenous injection of the contrast medium the
      metabolic activity of phagocytizing granulocytes increased steeply and returned
      to the initial value after 24 hours.

PMID- 7817569
TI  - [Laparoscopic cholecystectomy in older patients].
AB  - Operational risk of laparoscopic cholecystectomy in elderly patients has been
      retrospectively evaluated in 600 consecutive patients. Statistical correlation
      between age and risk factors as: biliary duct disease, adhesions, perforation of
      the gall bladder, necessity of extending of the incision, duration of the
      procedure, body temperature after LCh, morbidity, conversion rate from LCh to
      open cholecystectomy, has been tested. Despite of greater technical difficulties
      in elderly patients morbidity was not increased significantly. LCh in aged
      patients with cholecystitis is a safe method of choice.

PMID- 7817570
TI  - [Level of fructosamine as a measure of past glycemia and an indicator of diabetes
      control].
AB  - Fifty-four diabetics were studied carrying out during about two weeks
      determinations of 24-hour semiprofiles of glycaemia, and at the same time
      fructosamine concentration was determined. On the basis of glycaemia measurements
      the mean 24-hour glycaemia and the Mw index of Schlichtrull were calculated.
      Correlation was calculated between fructosamine concentration and the 24-hour
      past mean glycaemia, maximal 24-hour glycaemia and the index of diabetes control.
      The formula was developed for calculation of the past mean 24-hour glycaemia from
      fructosamine concentration.

PMID- 7817571
TI  - [Subpopulations of t and B lymphocytes, rosette tests, levels of immunoglobulins
      in peripheral blood and NBT test in the initial period of hemodialysis conducted
      with cuprophan or cellulose acetate dialysers in patients with chronic renal
      failure].
AB  - In 10 patients with chronic renal failure treated with haemodialyses (HD) T and B
      cell populations were determined in peripheral blood, together with
      immunoglobulin concentration and NBT test in the first two hours of the procedure
      using cuprophan and cellulose acetate dialysers. It was found that the per cent
      proportions of T4, T8 and T11 were not significantly changed. The proportions of
      B cells with sIg, sIgG, sIgM, sIgA were not significantly altered during HD with
      cuprophan dialysers. The per cent of B cells with sIg, sIgG decreased
      significantly during HD with cellulose acetate dialysers. The per cent
      proportions of active and late E rosettes decreased significantly, the per cent
      of stable E rosettes rose significantly, while that of EAC rosettes was not
      significantly changed in the initial HD period with the use of both dialyser
      types. IgG concentration rose significantly in the initial period of HD with
      either dialyser, while there was no significant change in the concentration of
      IgA and IgM. The value of the NBT test was not altered significantly during HD
      with either dialyser type.

PMID- 7817572
TI  - [Adenosine. Evaluation of diagnostic efficiency and therapeutic use in paroxysmal
      supraventricular tachycardia].
AB  - Paroxysmal supraventricular tachycardias are an important therapeutic problem and
      belong to the most frequently occurring arrhythmias. On the basis of a literature
      review the authors describe an alternative method of treatment of these
      conditions with adenosine and point also to its additional applications. The
      diagnostic use of adenosine and its safety in rhythmic undefined tachycardias
      with broad ventricular complexes is a therapeutic model worth of popularization.

PMID- 7817573
TI  - [Activities of certain endocrine glands in bronchial asthma].
AB  - The present reports on the effects of various levels of the endocrine system on
      the course of bronchial asthma are reviewed. Hypophyseal function in production
      of certain hormone and functioning of the hypothalamo, hypophyseal-thyroid, 
      adrenal, and -gonadal axis are discussed. Changes in the functions of endocrine
      glands may modify the course of allergic diseases.

PMID- 7817574
TI  - [5-Aminosalicylic acid in treatment of non-specific enteritis].

PMID- 7817575
TI  - [The structure of distracting-compressing stabilizers Dynastab DK intended for
      functional treatment of articular fractures].
AB  - The structure of the distracting-compressing stabilizers Dynastab DK intended for
      functional treatment of transarticular fractures is described. The stabilizers
      realize the idea of functional treatment of fractures outside the hospital bed
      making possible free moving around of the patient during the treatment. This has
      been made possible owing to building-in of a mechanical articulation imitating
      the physiological movement in the injured joint. The articulation in the
      stabilizer reduces also the load on the joint. In the stabilizers for the
      treatment of such fractures of the elbow joint and ankle joint the articulations
      are monoaxial (hinge-like). In the stabilizer for the treatment of the
      radiocarpal joint this is a hinge articulation making possible flexion in
      sagittal plane. In the stabilizer for knee fractures the movements in the injured
      joint are taken over by a mechanical articulation of special structure. The
      distracting-compressing action of the Dynastab DK stabilizers for the treatment
      of transarticular fractures is realized by the tension screw mechanism e.g. in
      the stabilizer for the treatment of knee joint fractures. In the case of
      stabilizers for ankle joint, radiocarpal joint and elbow joint this tension is
      provided by calibrated compressing springs.

PMID- 7817576
TI  - [Adult type RDS following disseminated bronchopneumonia in an infant with
      developmental anomalies of the branchial arches and pouches].

PMID- 7817577
TI  - [A case of renal clear cell sarcoma in a child with tuberous sclerosis].
AB  - A 10-year-old girl with sclerosis tuberosa was admitted to the Children's Health
      Centre for febrile states of unclear origin. Ultrasonography revealed the
      presence of renal tumour of clear cell sarcoma character in histopathological
      examination. Despite nephrectomy the child died several weeks after the
      operation. The authors pay attention to the fact that both clear cell sarcoma and
      most lesions observed in sclerosis tuberosa have common origin from the nervous
      crest so their coexistence seems no accidental. In view of the observed in
      sclerosis tuberosa proneness to neoformation, the authors stress the necessity of
      periodical examinations of the brain and internal organs, mainly kidneys and
      liver.

PMID- 7817578
TI  - [Hemobilia--rare cause of massive gastrointestinal hemorrhage].

PMID- 7817579
TI  - [Rare case of endogenous hepatic coma in a patient during the course of viral
      hepatitis A with a good outcome after arterialization of portal blood].
AB  - A case of endogenous hepatic coma during acute virus hepatitis A is reported.
      Arterialization of portal blood gave a good result.

PMID- 7817580
TI  - [Diphtheria in a 22-year old man].

PMID- 7817581
TI  - [Hospital infection of tropical malaria in Poland].
AB  - Two cases are reported of severe tropical malaria in individuals who never had
      been in the areas of endemic malaria. The infection occurred in hospital by a
      iatrogenic mechanism.

PMID- 7817582
TI  - [A case of Schmidt's syndrome].
AB  - A typical case of Schmidt syndrome is reported. The syndrome comprises signs of
      primary adrenocortical failure and hypothyroidism. Other endocrine and non
      endocrine immunopathies may be present also, such as type I diabetes, gonadal
      failure, Addison-Biermer anaemia, myasthenia gravis, vitiligo or alopecia areata.
      The possibility of these concomitant changes should be taken into account in the
      treatment of Schmidt syndrome. The case in a 52-year-old woman is reported in
      view of rare occurrence of thr syndrome and its few descriptions in the Polish
      literature as well as diagnostic difficulties.

PMID- 7817583
TI  - [Treatment of systemic lupus erythematosis with high doses of cyclophosphamide].
AB  - A case is presented of a female patient with systemic lupus erythematosus in whom
      a dramatic development was observed of life-threatening symptoms and signs from
      the central nervous system, haemopoietic system, and the kidneys. After
      introduction of therapy with high doses of cyclophosphamide administered in
      intravenous in combination with steroids, beneficial therapeutic effects were
      achieved. That suggests the conclusion that in early active form of lupus the
      risk of intensive treatment is acceptable.

PMID- 7817584
TI  - [Fibrates in the treatment of hyperlipidemia].

PMID- 7817585
TI  - [Arterial hypertension refractory to hypotensive treatment].
AB  - Lack of normalization of arterial pressure in spite of treatment of hypertension
      is most frequently caused by irregular and incomplete taking of hypotensive drugs
      or by erroneous medical instructions (drug interactions). "True" resistance to 3
      simultaneously administered hypotensive drugs in optimal doses may be caused by
      secondary hypertension. In a part of cases of refractory essential hypertension
      an increased insulin concentration is found. In the paper the importance is
      discussed of "resistance" to insulin in the development of hypertension.

PMID- 7817586
TI  - [Comparison of values for peak expiratory flow (PEF) measured with various
      devices in children].
AB  - Peak expiratory flow (PEF) (1/min) is a simple and reliable index of airway
      narrowing. The purpose of the work was the comparison of the PEF values obtained
      using two various measuring devices (Vitalograph Pulmonary Monitor and Clement
      Clarke mini Wright) in preschool children. The total number of 290 healthy and
      normally developed children aged from 4 to 6 years (142 girls and 148 boys) were
      studied. Each child carried out at least 5 PEF measurements with the above
      mentioned devices. The highest PEF values obtained using each of the devices were
      taken into account in further analysis. Statistically significantly higher PEF
      values were demonstrated in five- and six-year-old girls and in four- and five
      year-old boys, measured using the mini-Wright device as compared with the
      Pulmonary Monitor.

PMID- 7817587
TI  - [Congenital spherocytosis in children].
AB  - The clinical course and effects of treatment of congenital spherocytosis (CS)
      were analyzed in 28 children. In 10 cases the disease ran a severe clinical
      course. Jaundice, anaemia, and splenomegaly were the most frequent clinical signs
      which were significantly intensified during haemolytic crises. In 14 cases
      splenectomy was performed, obtaining in all children a regression of jaundice and
      anaemia. Before the operation two children were vaccinated with Pneumo 23. In
      asplenic children Debecillin was prophylactically used. Serious infectious
      complications were observed only in one patient.

PMID- 7817588
TI  - [Duodenogastric reflux in patients with functional dyspepsia].
AB  - In 66 patients with manifestations of functional dyspepsia and in nine volunteers
      duodenogastric reflux was studied by the cholangio-scintigraphic method. The
      results of the study were compared with the presence of the symptoms and sings
      and their intensity expressed in degrees, and with histopathological changes of
      gastric mucosa. In the symptomatic group the incidence of reflux was 42.4%. No
      reflux was found in the group of healthy volunteers. No relationship was
      demonstrated between duodenogastric reflux and the intensity of dyspeptic
      manifestations, nor between the reflux and the intensity of inflammatory changes
      in gastric mucosa.

PMID- 7817589
TI  - [Incidence of life-threatening congenital diseases in newborns of the Kujawy
      Pomerania region].
AB  - The study included 387 newborns treated in hospital for life-threatening in the
      years 1985-1991. Rather high differences were found in the number of newborns in
      various years. Seasonal of the anomalies was also observed. Most anomalies were
      found in the digestive tract, slightly less in the central nervous system. Higher
      incidence of anomalies was noted in northern forested parts of the region.

PMID- 7817590
TI  - [Renin-angiotensin-aldosterone system in peripheral blood and concentration of
      albumin and beta2 microglobulin in urine of women with chronic glomerulonephritis
      and chronic pyelonephritis].

PMID- 7817591
TI  - [Attempt at evaluation of alfacalcidol administered by an oral pulsatile method
      to chronically dialysed patients with advanced secondary hyperparathyroidism].
AB  - One of the basic complications of chronic renal failure is secondary
      hyperparathyroidism. The purpose of the work was an attempt at the assessment of
      the effectiveness of pulsating dosage of alfacalcidol as compared to daily
      dosage. Ten chronically dialysed patients were given for four months alfacalcidol
      in the mean dose 1 mcg daily, with simultaneous administration of calcium
      preparations and phosphorus-binding compounds. Every month the serum
      concentrations of total calcium and phosphorus were determined together with
      alkaline phosphatase activity. For another four months the same group of patients
      received alfacalcidol in pulsating way in dose of 0.1 mcg/kg body weight, once
      weekly. As compared with the period of treatment with daily doses of
      alfacalcidol, the change of treatment method to pulsating one caused a
      significant increase of calcemia as well as an evident decrease of alkaline
      phosphatase activity with a marked increase of phosphatemia.

PMID- 7817593
TI  - [Analysis of pharmacotherapy and it's effectiveness in ischemic heart disease and
      arterial hypertension, conducted by doctors in specialist and regional outpatient
      clinics].
AB  - On the basis of 1501 "Drug Disposal Charts" a comparative analysis was carried
      out of treatment schemas of ischaemic heart disease and arterial hypertension
      used by cardiologists and regional general practitioners, taking into account the
      effectiveness of treatment. Besides that the frequency was analysed of the
      reports by doctors on adverse reactions occurring during treatment.

PMID- 7817592
TI  - [Level of vitamin B12 and folic acid in blood serum of patients with senile
      dementia].
AB  - 85 cases over 65 were examined to establish concentration of B12 and folate acid
      in the serum. 25 cases of Alzheimer's Disease (AD), 33 patients with Multi
      Infarct Dementia (MID) and 27 non demented persons were collected. Folstein's
      Mini Mental State and Hachinski scales were chosen for the purpose of the study 2
      AD case (8%) patients demonstrated lower concentration of B12. No improvement
      after treatment was observed, although normalization of vitamin B12 level was
      reached. In elderly control group as well as in MID patients B12 and folic acid
      level in serum was in normal range. Statistically significant negative
      correlation between B12 serum concentration and dementia in woman population with
      MID was noted.

PMID- 7817594
TI  - [Pathomechanism of bronchial hyper-reactivity].

PMID- 7817595
TI  - [Myoglobinuria. Clinical aspects].
AB  - General data is presented on myoglobin structure and function, the pathomechanism
      of myoglobinuria and on its main causes. Attention was also paid to the most
      serious result of massive rhabdomyolysis-acute renal failure, taking into account
      the mechanism of its development. Apart from traumatic causes of myoglobinuria
      and myoglobinaemia, where the usefulness of these determinations is
      unquestionable, certain other diseases were compared in which the determination
      of the concentration of this haemoprotein is of important practical aspect.

PMID- 7817596
TI  - [Methods of gonad protection against effects of chemotherapy].
AB  - Together with increasing therapeutic effectiveness neoplastic diseases, the
      interest in late consequences of adverse effects of chemotherapy is increasing.
      Such problems include disturbances of gonad function. Treatment of neoplastic
      diseases leads frequently to infertility and hormonal disturbances resulting from
      damages to the gonads. Many attempts have been undertaken at protection of the
      gonads against unfavourable action of drugs. They are based mainly on the
      "interruption" of the hypothalamo-hypophyseo-gonadal axis in order to make the
      gonads quiescent. Other direction includes the influence on the metabolism of
      oncological drugs aimed at inhibition of the development of gonadotoxic
      derivatives. Another method includes appropriate choice of cytostatics:
      antimetabolites exert weaker unfavourable action on the gonads than alkylating
      drugs. The problem of gonad protection remains open. Searching is necessary for
      drugs without gonadotoxic action and effective methods of protection.

PMID- 7817597
TI  - [Prevention and treatment of chronic pain in oncologic patients].
AB  - The rules of three step therapy of chronic pain in terminal malignant has been
      presented. The need of priority of non narcotic drugs in retard form, oral or
      enteral administration and individual schedule out-pacing the occurring of pain
      has been stressed.

PMID- 7817598
TI  - [Difficulty in differential diagnosis of tumor-like structures in pulmonary
      hilus].
AB  - On the basis of two reported clinical cases, patient K. K. in whom preliminary
      diagnosis of tumour of the left pulmonary hilus was the result of valvular heart
      disease, and patient A. L. in whom similar symptoms, signs and radiological
      manifestations developed in the course of bronchogenous microcellular lung
      cancer, it was demonstrated that both the similar radiological picture and
      similar symptoms in the patients could be caused by totally different nosological
      entities. Effective differential diagnosis is of decisive importance especially
      for those patients in whom preliminary diagnosis of the pulmonary hilus turns out
      to have neoplastic basis. Such diagnosis can be made only in a well-equipped
      specialistic department.

PMID- 7817599
TI  - [A case of sarcoidosis in the orbit].
AB  - A case is described of a rare location of sarcoidosis in the orbit in a 43-year
      old woman. The complaints persisting for four weeks for which the patient sought
      medical advice were: oedema and left eyelid ptosis with narrowing of the eyelid
      fissure. In the diagnostic process, endocrine background of the disease was
      excluded, and a tumour was found in the orbit in computed tomography. The
      diagnosis of sarcoidosis was made on the basis of histopathological examination
      of the tissues removed from the orbit during surgical operation.

PMID- 7817600
TI  - [Prostatic abscess].

PMID- 7817601
TI  - [Multiorgan trauma].
AB  - A case is presented of a patient with multiorgan trauma. The main diagnostic
      problem was coexisting haemorrhage. Curable skin defects were healed after
      several covering them with intermediate thickness mesh grafts. The postoperative
      course was complicated with sepsis and acute non-inflammatory renal failure with
      polyuria.

PMID- 7817602
TI  - [Diagnosis of early forms of hypertension].

PMID- 7817603
TI  - [Evaluation of the usefulness of day care units for diabetic consultation].

PMID- 7817604
TI  - Chemotherapy of leprosy. Report of a WHO Study Group.

PMID- 7817605
TI  - [Self object and interpersonal emotions. Identification of own mirror image,
      empathy and prosocial behavior in the 2nd year of life].
AB  - This paper deals with the development of empathy during the second year of life.
      Empathy is defined as understanding another person's emotional state by
      vicariously sharing this state. In contemporary discussion, empathy is not
      clearly distinguished from emotional contagion, in which the Subject is
      indistinctly incorporated into the other person's mood. Most authors must
      therefore stipulate additional cognitive mechanisms, such as perspective taking,
      or even a theory of mind, to supply the empathic observer with the insight that
      it is, and remains, another person's emotional state which he shares. Contrary to
      this notion, the present paper proposes that insight is mediated by the
      particular quality of the empathical response itself and that self
      objectification is the only relevant precondition of empathy, since it allows
      drawing a clearcut distinction between the emotional domains of self and other.
      Since self-objectification is also responsible for recognizing oneself in a
      mirror, empathy should emerge simultaneously with self-recognition. This was
      tested in an investigation on 36 girls and boys aged 14 to 22 months. In two
      separate sessions the subjects underwent a "rouge test" for self-recognition and
      were confronted with a person in need, who demonstrated grief. Empathy was
      operationalized by prosocial interventions. The study replicates the results of a
      previous investigation (Bischof-Kohler, 1988, 1991) with a modified empathy
      eliciting situation. In both experiments, only those Subjects who recognized
      themselves tried to help, whereas non-recognizers stayed indifferent.

PMID- 7817606
TI  - [Especially gifted: especially happy, especially satisfied? On the self-concept
      of highly gifted and average children].
AB  - This study investigates the relation between intelligence and self-concept. 287
      fourth-grade elementary-school students (151 intellectually gifted children and
      136 children of average intelligence) participating in the Marburg Giftedness
      Project responded to an extended version of the Piers-Harris Children's Self
      Concept Scale. Results show that gifted children score higher in all facets of
      self-concept. However, this difference is only in the scale "intellectual and
      school status" statistically significant. Compared with gifted and non-gifted
      "achievers", gifted "underachievers" score lower in most self-concept facets.
      Independently of their intelligence level, children of this age group have
      developed a very positive self-concept.

PMID- 7817607
TI  - Response force and reaction time in a simple reaction task under time pressure.
AB  - The aim of this study was to examine the effect of effort on timing and force of
      simple reactions. To do this, we performed an experiment, arranged like a video
      game, in which these variables were measured under different time-pressure
      conditions. In accordance with our expectations reaction time was shorter and
      force amplitude larger when the time for responses was limited. These findings
      are discussed within the framework of Sanders' (1983) model of stress.

PMID- 7817608
TI  - Phlebitides--a survey.
AB  - Classification of phlebitides is difficult and none of the suggestions made so
      far has been internationally recognized. Already the definition of "primary" and
      "secondary" presents difficulties. For practical purposes the phlebitides are
      classified in this survey according to their importance as disease entities and
      their etiology. The role of phlebitis saltans as an idiopathic disease or as an
      indicator of underlying disorders is emphasized and the differential diagnosis
      between symptomatic skipping phlebitis and paraneoplastic thrombosis with
      secondary inflammation is outlined.

PMID- 7817609
TI  - [Respiration-dependence of cutaneous laser Doppler flow motion].
AB  - The aim of this study was to show and to quantify the breath-dependency of
      cutaneous fluxmotion in the volar proximal forearm using a new computer-aided
      system. A meanflux-related index (MI) representing the intensity of the influence
      of respiration on fluxmotion was calculated. There was a good correlation between
      MI and the rate of respiration under spontaneous breathing: the lower the rate of
      respiration, the higher the value of MI. Prescribing a constant breathing rhythm
      amplifies this frequency-dependent effect. According to occurrence of low rates
      of respiration (< 12/min) also under physiological conditions the respiration
      should be simultaneously recorded while assessing fluxmotion.

PMID- 7817610
TI  - [Effect of rejuvenation on the rheologic properties of stored erythrocytes].
AB  - Buffycoat free red cell concentrates in a medium composed of sodium chloride,
      adenine, glucose and mannitol (SAGM) stored for 42 days at +4 degrees C were
      rejuvenated by a solution which contained pyruvate, inosine, disodiumphosphate
      and adenine (PIPA). The rheological behaviour of red cells was measured before
      and after rejuvenation by viscosimetry of red cell suspensions (hematocrit 45%)
      at various intervals during the storage period. The deformability of the red
      cells during storage was determined also before and after rejuvenation by
      measurement of the viscosity of hard packed cells (hematocrit 98%). The results
      show improvement of the rheological properties by rejuvenation. Moreover it is
      shown that incubation of the red cells at 37 degrees C for two hours without
      rejuvenation solution decreases the viscosity.

PMID- 7817611
TI  - [Noninvasive studies of macro- and microcirculation in follow-up of
      femoropopliteal bypass operation in IIb peripheral arterial occlusive disease].
AB  - In 42 patients with POAD in stage IIb the blood-flow in the common femoral artery
      and in the superficial femoral artery was measured before, 10 days after, 3 and
      12 months after femoro-popliteal bypass surgery. Blood-flow was detected
      noninvasively using a multichannel ultrasound computer system (MAVISR).
      Simultaneously Doppler pressure, skin temperature and tcPO2-values were measured.
      Thereafter the patients had to undergo treadmill tests (painfree and maximal
      walking distance). Compared to healthy volunteers preoperative blood-flow was
      significantly (p < 0.001) reduced in the common femoral artery and in the
      superficial femoral artery. Postoperatively the blood-flow increased
      significantly (p < 0.001) in patients with an open bypass. This increase could
      still be demonstrated up to one year after bypass surgery. Surprisingly, a
      significant (p < 0.01) postoperative rise in blood-flow was also observed in the
      non-operated leg. Doppler pressure, tcPO2-values (calf) in the operated leg and
      walking distance increased significantly (p < 0.001). The MAVISR as a noninvasive
      procedure allows to check the further development of the bypass-function
      independently of subjective influences, because quantitative changes in blood
      flow are documented.

PMID- 7817612
TI  - Lipoprotein (a) in peripheral arterial occlusive disease.
AB  - Recent studies have shown high levels of lipoprotein (a),--Lp(a)-, an atherogenic
      and thrombogenic lipoprotein, are considered a risk factor for coronary heart
      disease. This study evaluated Lp(a) levels, as well as other lipid factors, in a
      group of 45 patients affected by stage II peripheral arterial occlusive disease
      (PAOD). An age-, sex- and Body Mass Index-matched group of healthy controls was
      also recruited. Exclusion criteria were diseases or drugs which could alter Lp(a)
      levels. Alterations in lipid profiles, which are often associated with PAOD, were
      observed in the patients. Lp(a) levels did not differ significantly in the two
      groups (median 16.4 mg/dl, range 10-104, in PAOD and 9.9 mg/dl, range 7.4-66.7,
      in controls and means 21.7 +/- 17.5 mg/dl and 21.2 +/- 16.8 mg/dl respectively)
      but in 51% of the controls Lp(a) levels were < 10 mg/dl compared with 20% of the
      PAOD patients (p < 0.05).

PMID- 7817613
TI  - Duplex ultrasound scanning for diagnosis of aortoiliac and femoropopliteal
      arterial disease.
AB  - Forty patients with symptomatic aortoiliac and/or femoropopliteal occlusive
      arterial disease subjected to angiography were studied with duplex
      ultrasonography. The duplex scanning of the aortic, iliac, femoral and popliteal
      segments had a sensitivity of 93% in detecting significant stenoses and a
      specificity of 91%. The positive and negative predictive values were 75% and 98%,
      respectively. The sensitivity was relatively low in low-flow segments distal to
      total occlusions especially in patients with severe iliac disease and multiple
      distal femoropopliteal lesions. The results demonstrate the reliability of duplex
      scanning in detecting aortoiliac and femoropopliteal lesions.

PMID- 7817614
TI  - Screening for proximal deep venous thrombosis using B-mode venous ultrasonography
      following major hip surgery: implications for clinical management.
AB  - Despite antithrombotic prophylaxis, deep vein thrombosis (DVT) remains a frequent
      complication following major hip surgery. Most of the postoperative DVTs are
      asymptomatic but may result in fatal pulmonary embolism. Thus, detection of these
      events remains a clinical challenge. The present study evaluated prospectively
      the clinical usefulness of a systematic screening for proximal DVT in 173
      consecutive patients undergoing major hip surgery and given systematic
      antithrombotic prophylaxis. On the 12th postoperative day, real-time B-mode
      ultrasonography of lower limbs veins detected 12 patients (7%) with proximal DVT.
      None of the individual or surgical characteristics of the patients could help to
      predict postoperative DVT. Because the sensitivity of ultrasonography for
      diagnosing DVT in asymptomatic patients may be low and because we did not screen
      for distal DVT, it was speculated that up to half proximal DVT and up to 75% of
      all DVT might have been missed by the screening. Therefore, low-dose oral
      anticoagulation with an INR 1.5-2.0 might be the most cost-effective modality in
      the postoperative period after the initial perioperative prophylaxis with low
      dose heparin, low-molecular-weight heparins or intermittent pneumatic compression
      boots. Oral anticoagulant treatment might be continued for a total duration of 6
      weeks, thereby also providing efficient therapy of undiagnosed distal DVT and
      prolonged for 3 months in patients with proximal DVT proven by systematic
      ultrasonographic screening at the time of discharge. The benefit-to-risk ratio of
      this management strategy deserves further evaluation in a specially designed,
      prospective trial.

PMID- 7817615
TI  - [Neuromonitoring in carotid surgery: possibilities and limits of transcranial
      Doppler ultrasound].
AB  - In order to evaluate the suitability of transcranial Doppler sonography as an
      intraoperative monitor in carotid surgery, we compared measurements of mean blood
      flow velocity in the ipsilateral middle cerebral artery with the cortical
      response of somatosensory evoked potentials in a prospective study of 176 carotid
      operations. SEP recording was readily feasible during all procedures and by means
      of SEP loss all patients at risk for critical cross-clamp related cerebral
      ischemia were reliably identified. In contrast, TCD could not be used for
      assessment of cerebral hemodynamics in more than 40% of patients. What is more,
      in high risk patients with intraoperative loss of SEP, TCD could not be performed
      in 74% of cases. This high rate of failure limits the usefulness of TCD as an
      intraoperative monitor and detracts from the additional benefit of identifying
      cerebral embolism and hyperperfusion as potential causes of neurological
      deficits. In contrast to SEP recording, TCD cannot be recommended as a routine
      monitor in carotid surgery.

PMID- 7817616
TI  - [Experimental retroperitoneoscopic lumbar sympathectomy].
AB  - The present study was designed to support the hypothesis that lumbar
      sympathectomy could be performed by minimal invasive surgery. In a porcine
      experiment, under laparoscopic vision control, a pneumoretroperitoneum was
      established through a direct retroperitoneal access for dissecting the
      retroperitoneal tissue layers and resecting the lumbar sympathetic trunc. The
      connective tissue septae were separated without any problems by blunt dissection
      under vision through the retroperitoneally inserted laparoscope. After exposure
      of the retroperitoneal organs and identification of specific landmarks, the
      resection of the lumbar sympathetic trunk was performed. We conclude that lumbar
      sympathectomy can be easily performed by minimal invasive surgery.

PMID- 7817617
TI  - [Follow-up of infra-inguinal bypass operations: value of the peak systolic
      velocity and arm-ankle index for evaluation of femorodistal reconstructions].
AB  - In a prospective study, the efficacy of noninvasive surveillance techniques
      including measurement of ABI and duplex-derived velocity parameters was studied
      after 74 infrainguinal arterial reconstructions. A decrease of ABI > or = 0.2
      compared with prior examinations was considered abnormal. Results of the duplex
      scan were interpreted as abnormal when PSV was less than 45 cm/sec or greater
      than 200 cm/sec or when an interval decrease of greater than 30 cm/sec occurred.
      All patients meeting any of these criteria during the follow-up examinations were
      subjected to i.a. DSA. The combination of all duplex velocity criteria was
      significantly more sensitive to identify a failing graft than was measurement of
      ABI (90% vs. 18%; p = 0.00004). When independent variables (ABI- and PSV
      criteria, monophasic curve configuration) were entered into a logistic regression
      multivariate analysis, the model proved to be effective (F-value 5.551; df 4.8;
      R2 = 0.735; significance 98.03%; p < 0.02) in predicting angiogram findings
      (dependent variable). ABI measurements (significance 4.75%; p > 0.95) and the
      presence of a monophasic curve configuration (significance 89.58%; p > 0.1)
      failed to reach significance in the multivariate analysis. By excluding these
      latter parameters, the statistical power for the model could be improved (F-value
      1036.57; df 2.1; R2 = 0.999; significance 97.69%; p = 0.0231): As a result normal
      PSV criteria indicated normal and abnormal angiographic findings in 83 and 17%,
      respectively. A PSV less than 45 cm/sec or greater than 200 cm/sec was suggestive
      of an abnormal angiogram in 80% and of a normal angiogram in 20%. The
      corresponding figures for a PSV interval decrease > 30 cm/sec were 71% and 29%.
      In conclusion, PSV parameters were found to be measurably more accurate to
      identify a failing graft than was measurement of ABI.

PMID- 7817618
TI  - The influence of chronic treatment with betablockade and angiotensin converting
      enzyme inhibition on the peripheral blood flow in hypertensive patients with and
      without concomitant intermittent claudication. A comparative cross-over trial.
AB  - In a comparative cross-over trial we examined the influence of the betablocker
      bisoprolol and the ACE-inhibitor lisinopril on the peripheral blood flow of 2
      groups of hypertensive patients with and without concomitant intermittent
      claudication. In 11 patients with hypertension without peripheral arterial
      obstructive disease and 11 patients with hypertension and claudication we
      assessed the blood pressure, leg blood flow, vascular resistance, walking
      distance, transcutaneous oxygen consumption and Laser-Doppler flow after
      treatment of one month with 10 mg bisoprolol once daily or 20 mg lisinopril once
      daily. The walking distance of patients with claudication improved in all
      patients while participating in an exercise program. For both treatment groups
      this improvement was significant (p < 0.05) compared to baseline, from 264 m at
      baseline to 313 m with bisoprolol and to 400 m with lisinopril. The difference
      was not significant between the both drugs. In patients without peripheral
      vascular obstructive disease we found a significant (p < 0.05) reduction in blood
      flow for both drugs. The peripheral blood flow parameters of 38 legs showed no
      statistical significant effect of bisoprolol nor lisinopril on the local vascular
      resistance at rest, after occlusion or after exercise.

PMID- 7817619
TI  - [Normal kidney function of the transplanted kidney in ipsilateral pelvic artery
      occlusion 15 years after transplantation. A case report].
AB  - A case of a 61-year-old women 15 years after right-sided renal transplantation is
      discussed. She suffered from rest pain in her right leg. Examinations revealed an
      occlusion of the right common iliac artery without signs of renal dysfunction or
      severe hypertension. After performing a extraanatomic femoro-femoral crossover
      bypass the patient had improved leg perfusion without a change in renal function.

PMID- 7817620
TI  - [Extensive aneurysm of the internal carotid artery with free floating round
      thrombus].
AB  - A large asymptomatic aneurysm of the internal carotid artery containing a free
      floating thrombus was detected in a 90-year-old woman. The alteration was
      documented by duplex sonography of the extracranial carotid arteries. At a second
      examination 4 days later the thrombus was observed to be fixed to the dorsal and
      distal aneurysm wall. With regard to the age and reduced general state of health
      of the patient, invasive diagnostic examinations and reconstructive surgery were
      not indicated and the patient was released in a good condition.

PMID- 7817621
TI  - [Spontaneous limited dissection of the external iliac artery. Case report after
      14 year follow-up].
AB  - The case of a limited dissection of the external iliac artery in a 31-year-old
      woman is described. The clinical symptomatology was that of an acute ischemia of
      the right lower extremity. Histology revealed the existence of a cystic
      Medionecrosis. With reference to the literature, the clinical and surgical
      aspects are discussed.

PMID- 7817622
TI  - [Spontaneous, massive liver hemorrhage as a complication of thrombolysis with
      ultra-high dose streptokinase in deep thrombophlebitis].
AB  - We report on a rare case of spontaneous, life-threatening liver bleeding as a
      major complication of thrombolysis using short-term, ultrahigh streptokinase in
      deep venous thrombosis. The event occurred in a female patient (age 40 years) who
      presented no contraindication to thrombolytic therapy. Intraabdominal bleeding
      was suspected during intravenous streptokinase infusion. Emergency laparotomy
      revealed four liter of unclotted blood resulting from two ruptured subcapsular
      liver haematomas. Local haemostasis was achieved and the integrity of the liver
      restored. Multiple transfusions of red blood cells, fresh frozen plasma and
      fibrinogen were given. The postoperative period was uneventful and the patient
      recovered gradually. The patient could be discharged from the hospital in good
      health. Diagnostic and therapeutic approaches to this rare complication of
      thrombolysis are discussed. Additionally, a brief review of previously reported
      cases is provided.

PMID- 7817623
TI  - [Nutritional balance of the diet of the adult residents of Geneva].
AB  - Diet of the Swiss population has probably changed over the last 10 years, but
      these changes have not been recorded yet by nutritional studies. In the present
      study, 3 registered dieticians interviewed over the telephone 626 adults,
      resident of Canton Geneva, using a 24 hour recall. Interviews were performed
      during the 7 days of the week. Participants were randomly selected according to
      their age, sex and nationality. Participation was 80%. The following caloric (C)
      and nutritional intakes in proteins (P), lipids (L), carbohydrates (CH) and
      alcohol (A) were recorded: In non Swiss men: C = 2464 kcal/j., P = 16.2%, L =
      32.4%, CH = 44.4%, A = 7.0%; in Swiss men: C = 2752 kcal/j., P = 15.3%, L =
      34.0%, CH = 43.5%, A = 7.1%; in non Swiss women: C = 1897 kcal/j., P = 16.4%, L =
      35.1%, CH = 46.5%, A = 2.4%; in Swiss women: C = 1865 kcal/j., P = 15.0%, L =
      35.3%, CH = 46.0%, A = 3.2%. Total caloric intake and iron intake decreased with
      age. Older women ate less calcium than younger. In summary, the most important
      determinants of diet are age and sex. Proportion of lipids is relatively low in
      both men and women. Small differences related to nationality were observed in
      men.

PMID- 7817624
TI  - [Development and validation of a semi-quantitative food questionnaire based on a
      population survey].
AB  - An auto-administered, semi-quantitative food frequency questionnaire was
      developed to assess evolution of dietary habits in the Geneva population. For
      this purpose 626 adults, aged 35 years or more and residents of Canton Geneva,
      were interviewed using a 24 hour recall technique. The questionnaire comprises
      the 80 food items or homogeneous food groups contributing to more than 90% of the
      intake in calories, proteins, lipids, carbohydrates, alcohol, cholesterol,
      calcium, vitamin D and retinol, and to more than 85% of dietary fibers, carotene
      and iron. To complete the food frequency questionnaire, participants indicate for
      each of the 80 food items or groups their frequency of consumption and whether
      their usual portion is equivalent to a reference portion listed in the
      questionnaire (median portion in the sample), smaller (first quartile of the
      portion distribution in the sample) or larger (third quartile of the portion
      distribution in the sample). The questionnaire can be filled in about 20 minutes.
      To test the new questionnaire we submitted it to a sample of 27 men and 29 women
      randomly selected from the 626 subjects who participated to the original survey.
      Mean intakes obtained using the food frequency questionnaire agree well with
      those obtained using the 24 hour recall for all subgroups defined by age, sex or
      nationality. The food frequency questionnaire tends to slightly underestimate the
      absolute intakes of alcohol, fibers and calcium since it is based on a subsample
      of all food items consumed according to the 24 hour recall interviews. These
      results suggest that the semi-quantitative food frequency questionnaire is a good
      alternative to 24 hour recalls to assess mean nutrient intakes in the adult
      population of Canton Geneva.

PMID- 7817625
TI  - ['Chasing the dragon' in Switzerland: results of an expert questionnaire].

PMID- 7817626
TI  - [Current musculoskeletal symptoms in peri and postmenopausal women: results of a
      multicenter population epidemiological study. The EVOS Study Group].
AB  - Within the European vertebral osteoporosis study four stratified systematic
      samples of German residents aged 50-79 in Lubeck, Heidelberg, Jena and East
      Berlin have been drawn. Overall 4628 subjects were included, of whom 4385 were
      contactable and 3106 (71%) responded to the postal questionnaire enquiring about
      rheumatic complaints "today". 2348 (54%) followed an invitation to a medical
      examination in which a specific gynaecological history was taken. The prevalence
      of current back-, neck- and joint-pain is consistently higher in females than in
      males in all age groups. Females show a peak prevalence in the age group 55-64.
      104/1134 women were pre- or perimenopausal. 1030 women had not had their period
      for at least 13 months and were classified as "postmenopausal". Neither the
      menopausal status nor the duration of the postmenopause were statistically
      significantly associated with the frequency of the three rheumatic complaints.

PMID- 7817627
TI  - The Swiss HIV Cohort Study: rationale, organization and selected baseline
      characteristics.
AB  - OBJECTIVES: This paper describes the rationale and design features of the Swiss
      HIV Cohort Study (SHCS) and the baseline characteristics of participants enrolled
      up to March 31st 1993. The objectives include epidemiological, clinical and
      laboratory research. DESIGN: The SHCS is a prospective cohort study of HIV
      infected adolescents and adults seen at the outpatient clinics of the Swiss
      University Hospitals in Basle, Berne, Geneva, Lausanne and Zurich and the
      Cantonal Hospital St. Gall. The multicentre collaboration was initiated in
      September 1988 by the Swiss Federal Office of Public Health. Data collected prior
      to this date by several participating centers using a similar protocol were
      included, the earliest records dating back to 1982. Follow-up visits are
      scheduled every 6 months. ENROLLMENT: As of March 31st 1993, 6253 participants
      (M: 4580, F: 1675) were included with a total of 16015 person-years of follow-up
      (mean 2.6 years). HIV transmission categories were 46% intravenous drug users
      (IDU), 32% men who had sex with men (MSM), 18% heterosexual contacts (HET) and 4%
      other. The proportion of MSM among male participants decreased from 62% in 1985
      to 40% in 1987, to remain stable thereafter. The proportion of IDU among males
      was around 40% throughout, whereas in females, there was a pronounced decline
      from 90% IDU in 1985 to 50% in 1992. Conversely, there was a striking increase in
      registrations of women presumably infected by HET, from 8% in 1985 to 50% in
      1992. Among men, the proportion classified as HET increased from 2% to 15%. It is
      estimated, that a large proportion of all Swiss AIDS patients (70%) and HIV
      infected individuals (32%-47%) are enrolled in the Swiss HIV Cohort Study. Losses
      to follow-up, however, are common. CONCLUSIONS: The SHCS serves multiple purposes
      as a research project, as infrastructure for multidisciplinary research and as a
      tool to improve patient care. Several international and national trials, post
      marketing surveillances and expanded access protocols were or still are based
      upon its infrastructure. The large number of female participants and of
      participants AIDS-free at entry, make the database especially valuable.

PMID- 7817628
TI  - WHO predicts increase in tuberculosis deaths: map shows fatal spread of TB
      epidemic.

PMID- 7817629
TI  - WHO report on infant and young child nutrition: global problems and promising
      developments.

PMID- 7817630
TI  - [Psychosomatic medicine, psychoanalysis and human biology today].

PMID- 7817631
TI  - [Loss, grief and depression: considerations based on emotion research].
AB  - After clearing up the terminology within the field of bereavement the
      significance of different types of attachment to the lost object for the mental
      development after the loss is discussed. Similarities and differences of three
      phase models of the bereavement process are worked out. The heuristic value of
      these models is set into balance to the danger of their misuse for nailing down
      somebody about quality and duration of his "Trauerarbeit". Sadness as an affect
      is described within an general schema for the understanding and description of
      emotions. According to this schema affects are depicted internally as specific
      cognitive structures. The one of the grief affect predisposes to traumatic
      developments. Intercultural data show that identificatory processes are highly
      important for a benevolent ending of bereavement processes. The actual tendency
      to consider such phenomena as pathological is cleared up through a comparison of
      sadness, depression and depressivity. Departing from different types of
      attachment, bereavement courses and identificatory processes possible malign
      endings of bereavement processes are described.

PMID- 7817632
TI  - [Relation between research and practice in analytic psychotherapy].
AB  - The technique of psychoanalytic treatment as an objective, operative
      technological theory inevitably experiences a subjective refraction on analyst's
      personality and his or her own cognitive and interactional styles influencing
      therapeutic efficiency. Systematic clinical trials of treatment data integrating
      motions from psychoanalytic, social and cognitive science, reconcile the gap
      between research and practice, between basic science and application. It will be
      discussed how empirical research can delineate therapists' cognitive and
      perceptual skills and the process of transformation from declarative to
      procedural knowledge, further elaborated in reciprocal connection with practice.
      The models of Structural Analysis of Social Behavior (SASB) and Cyclic
      Maladaptive Pattern (CMP) are especially considered. We will also discuss the
      consequences for training in psychoanalysis.

PMID- 7817633
TI  - [Psychoanalysis on trial? On the empirically disguised professional politics of
      Klaus Grawe].
AB  - In the introduction the question is answered, why the meta-analysis of Klaus
      Grawe, Ruth Donati und Friederike Bernauer should be taken seriously by
      psychoanalysts. Above all is a problem, that implicit in this meta-analytical
      evaluation there are methods and criterions of the empirical behavioristic
      psychotherapy research, which favour automatically the behavioral therapy. The
      abuse of empirical research to denigrate psychoanalytic training and training
      institutes is criticized. Reflection on adequate assumptions for a
      psychoanalytical psychotherapy research is pleaded for and some requirements are
      mentioned. In view of the mentioned deficiencies the claim of Grawe et al. to
      deduce important conclusions on their meta-analysis, must be evaluated as false.

PMID- 7817634
TI  - [Critical comments on the statistical methods in Grawe, Donati and Bernauer:
      "Change in psychotherapy. From confession to profession"].
AB  - In the meta-analysis "Changing Psychotherapy" by Grawe, Donati and Bernauer
      different psychotherapeutic methods are compared based upon published therapy
      studies. Hereby the authors claim also to have proven with statistical methods
      that certain kinds of therapy are more effective than others. I show here that
      the descriptive and inductive methods used are not able to withstand a critical
      examination; they are incorrect and in most cases even inadmissible. The results
      of my examination show that there are four points of critique: 1. The question of
      how effective a kind of therapy is, according to Grawe's criteria, depends more
      on the number of variables and their measurements with which a therapy is judged
      than on the number of patients examined in the single studies. 2. Grawe does not
      distinguish between dependent and independent variables or measurements; every
      measurement of each variable is included in his methods with the same weight. 3.
      The different effect variables used to evaluate the therapic process are mostly
      represented on varying ordinal scales which are incomparable with each other.
      Grawe treats these scales as if they were comparable, often even as if they were
      metric. 4. All five statistical methods (counting significances, binomial test,
      profile of difference values, t-test, Wilcoxon-test) with which Grawe evaluates
      the results of the single studies are inadmissible because the conditions
      required are not met. In sum: The conclusions stated in the meta-analysis cannot
      be seen as being statistically validated or statistically proven.

PMID- 7817635
TI  - [Chaos theory and psychoanalysis: the fluid nature of the soul].
AB  - Progress in the new science of chaos has made it possible for scientists of
      several different disciplines to extend their understanding of complex systems
      and to quantify some phenomena which are called transition states. These
      transitions occur when the nature of system changes noticeably, for example when
      a fluid changes from a laminar to a turbulent flow. Nonlinear systems (which are
      best modelled by chaos) are described in this article and are compared to the
      psychoanalytic model of the soul. Some psychoanalytic phenomena are examined with
      methods of the chaos principles. The author claims that a sufficient number of
      interrelations between operative models in the disciplines which have profited
      from the application of chaos principles and psychoanalytic models of the soul
      exist in order to justify theoretical and experimental efforts to use these
      principles. These efforts could enrich our understanding of the soul and suggest
      a new methodology for psychoanalytic research.

PMID- 7817636
TI  - Growth performance, haematological traits, meat variables, and effects of
      treadmill and transport stress in veal calves supplied different amounts of iron.
AB  - Effects of serum iron (Fe), haematological variables and on blood lactate levels
      before and after treadmill exercise or transport to the slaughterhouse, on meat
      traits, and on growth performance of feeding milk replacer (MR), planned to
      contain 10, 20, 30, 40, 50 or 80 mg Fe/kg, were studied in veal calves. If
      supplied less than 50 mg Fe/kg MR, calves developed hypoferraemia and anaemia,
      the degree of which was dependent on Fe intake. Serum Fe concentration,
      saturation of transferrin with Fe and the degree of anaemia in calves fed 20 or
      10 mg Fe/kg MR were nearly identical. Serum Fe concentration and haematological
      traits barely changed in calves fed 50 mg Fe/kg MR during the growth trail, but
      serum Fe concentration increased when MR contained 80 mg Fe/kg in calves fed 50
      or more Fe/kg MR. Growth performance was smaller in calves fed 10 mg Fe/kg MR
      than in those fed greater amounts of Fe/kg MR. Carcass taxation was inversely
      related to Fe intake. In conclusion, MR containing only 10 mg Fe/kg caused marked
      anaemia and reduced growth performance. Feeding MR with only 20 mg Fe/kg is not
      necessarily sufficient to prevent development of severe anaemia. Feeding MR with
      50 mg Fe/kg would seem to be physiologically the most appropriate amount of Fe
      for veal calves, but was too high for acceptable carcass taxation.

PMID- 7817637
TI  - Iron status, erythropoiesis, meat colour, health status and growth performance of
      veal calves held on and fed straw.
AB  - Two experiments were designed to study the iron (Fe) status in veal calves (62
      intact males) fed and held on straw. In experiment 1, two groups were fed 20 mg
      Fe/kg milk replacer (MR) and held unattached on rye or barley straw litter. In
      experiment 2, groups were fed 20 mg Fe/kg MR and held unattached on rye straw
      litter or on sawdust or attached on wooden slatted floors without straw litter or
      were fed 50 mg Fe/kg MR and held unattached on sawdust. Fe concentrations in
      tested straw sorts (rye, barley, wheat, triticale) were similar and ranged from
      15 to 85 mg Fe/kg dry matter. Growth performance and health status were not
      significantly influenced by Fe intake through MR or straw. Straw intake in the
      group fed straw was greater (P < 0.01) at the end than at the start of the growth
      period, but intake of different straw sorts was similar. Calves fed 20, but not
      those fed 50 mg Fe/kg MR, developed marked hypoferraemia, but only moderate
      anaemia. Total iron binding capacity (TIBC) was significantly (P < 0.05) and
      transferrin (Tf) concentration was numerically higher in calves fed 20 than in
      those fed 50 mg Fe/kg MR on slaughter day. TIBC and Tf were positively correlated
      (r = 0.63). Haemin concentration and lightness of m. rectus abdominis were
      significantly (P < 0.01), whereas myoglobin concentration was numerically greater
      in calves fed 50 than in those fed 20 mg Fe/kg MR. In conclusion, haematological
      and blood chemical parameters and meat colour were influenced only by high Fe
      intake through MR, but not if calves were held on straw litter or were fed straw.

PMID- 7817638
TI  - Evaluation of halothane as an anaesthetic in camels (Camelus dromedarius).
AB  - Halothane as an anaesthetic was evaluated in 12 adult camels, thiopentone being
      used as an induction agent. In six camels, clinical signs and haematological and
      blood biochemical changes were investigated while in other six haemodynamic, acid
      base and blood gas changes were monitored. The dose of thiopentone required to
      ensure intubation for halothane anaesthesia was 7.25 +/- 0.33 mg/kg. A modified
      technique of tracheal intubation was found to be safe and quick. During halothane
      administration all anaesthetic effects were predictable. Complete recovery
      occurred in 39.5 +/- 9.8 min after discontinuation of halothane administration.
      Halothane moderated the thiopentone-induced tachycardia. The mean arterial
      pressure decreased significantly. There was an increase in the arterial carbon
      dioxide and venous oxygen tension during halothane anaesthesia and development of
      hypoxaemia after its discontinuation. The alanine aminotransferase values
      increased during recovery, while plasma sodium, potassium and calcium decreased.
      Halothane appears to be safe for camels. However, to avoid hypoxaemia in the
      immediate post-anaesthetic period, oxygen administration should be continued.

PMID- 7817639
TI  - Radiological aspects on the course of development of porcine epiphyseal
      osteochondrosis (OCD) from 42 up to 147 days of age.
AB  - The articular-epiphyseal (A-E) cartilage complex of the distal humeral and
      femoral epiphyseal condyles of eight intact pigs (4 male & 4 female) of the same
      age were radiologically examined every 3 weeks, beginning at 42 days up to 147
      days of age; to determine the age of onset, the course and trend of development
      of osteochondrosis (OCD). The earliest Dyschondroplasia (Osteochondrotic) lesions
      were demonstrated radiologically in the A-E complexes of the humeral condyles of
      42-day-old pigs and in the femoral condyles at 63 days of age. Thus the
      radiographic examination of live animals to demonstrate subchondral radiolucency
      typical for OCD lesions in the condylar A-E complexes of pigs is not of limited
      value until the animals were > 100 days old as indicated in earlier reports. Also
      the course of further development of OCD lesions associated with A-E complexes
      was followed. The radiolucency was seen to develop to a certain extent, and then
      either to regress, and stabilize or even to progress as the animal grows. Some
      lesions regressed completely. Also some of the regressed lesions may become
      active again and become progressive. However, the course of development of
      femoral condyle A-E complexes OCD lesions was seen to be progressive
      continuously, or progressive then stable and then progressive again. The
      regressive course and trend of osteochondrotic lesions was not observed in the
      femoral condyle A-E complexes up to day 147 of age. Therefore, the course and
      trend of development of the A-E complexes OCD is not constantly the same.

PMID- 7817640
TI  - The sequelae of distal ulna physeal dyschondroplasia (osteochondrosis) lesions in
      breeding swine--a radiological investigation in Danish Landrace pigs.
AB  - A radiological follow-up study of osteochondrotic lesions in the distal ulna was
      carried out in 58 Danish Landrace breeding sows for a period of 15 months
      (October 1992 to December 1993). This was part of a major project involving the
      radiological investigation of articular-epiphyseal and physeal development to
      investigate osteochondrotic lesions in pigs. The radiological lesions were graded
      from 1 to 5 with increasing severity. It was observed that not all pigs passed
      through all grades. Only 21% of the pigs had no radiological osteochondrotic
      lesions (grade 1) during the first radiography series. After 5-7 months, the
      number of pigs without osteochondrotic radiological lesions were observed to have
      increased dramatically (21-69%), but the converse was true for grades 2 (mild), 3
      (moderate), 4 (severe) and 5 (very severe): (33-17%), (21-9%), (19-5%) and (7-0%)
      respectively. This was observed with increasing age and weight. The 3rd
      radiography series indicated that the percentage of pigs without osteochondrotic
      lesions increased up to 82%, and that grades 2, 3, and 4 had fallen to 14%, 2%
      and 2% respectively, while grade five remained at 0%. This indicated that the
      distal ulna osteochondrotic lesions can be important in breeding pigs during the
      period of growth before first pregnancy. During the first pregnancy the
      osteochondral ossification fault can be corrected, and the lesions heal. The ulna
      growth plates were not closed at the second, but mostly closing during the third
      radiography series.

PMID- 7817641
TI  - A study on the efficacy of a phospholipid solution in dogs with aspirin-induced
      thrombocytopathy.
AB  - The aim of the present study was to test the haemostyptic properties of a
      phospholipid complex with platelet factor-3 (PF-3) activity in platelet-dependent
      haemostatic disorders. The substance was investigated in an animal model
      comprising six investigational groups (five dogs each). A thrombocytopathy was
      created in the dogs belonging to groups 1-5 by intravenous administration of 20
      mg/kg body weight (BW) acetylsalicylic acid (ASA). Two hours later a human
      albumin solution (5%) (control group) or a phospholipid complex with PF-3
      activity was injected or infused intravenously in different dosages. In dogs pre
      treated with ASA, injection of 2 ml/kg BW of the phospholipid complex shortened
      capillary bleeding time, which was prolonged as a consequence of ASA-treatment.
      This effect lasted for 4 h at least. The capability of the platelets to aggregate
      increased 5 min after intravenous injection of the phospholipid without
      differences in the respective groups. At the same time platelet counts dropped to
      approximately 50%, but increased again distinctly after 30 min. When the
      phospholipid complex was administered to clinically healthy dogs who had not been
      treated with ASA, this resulted in prolongation of the capillary bleeding time as
      well as a significant platelet drop in the peripheral blood. Although these were
      only short-term effects after administration of the phospholipid complex, a
      disadvantageous effect cannot be excluded in patients suffering from haemorrhagic
      diathesis. For this reason, a phospholipid complex with PF-3 activity cannot be
      recommended as a therapeutic agent for platelet-dependent coagulation disorders
      in the dog.

PMID- 7817642
TI  - Polioencephalomalacia induced with amprolium in buffalo calves--clinicopathologic
      findings.
AB  - Polioencephalomalacia was induced in eight buffalo calves, 6-12 months old, by
      drenching amprolium (300 mg/kg body weight per day) for 29-55 days. Four buffalo
      calves of the same age group were drenched with tap water only and served as
      control. Blood samples were collected at different intervals during amprolium
      administration until the onset of clinical signs. Cerebrospinal fluid was also
      collected prior to amprolium administration and at the onset of clinical signs. A
      significant progressive decrease in erythrocyte transketolase (TK) activity and
      an increase in the percent of thiamine pyrophosphate (TPP) effect were observed
      in amprolium-fed calves during amprolium administration until the onset of
      clinical signs. There was a significant increase in blood lactate and blood
      pyruvate concentrations and a significant decrease in lactate/pyruvate ratio at
      the onset of clinical signs. Serum electrolyte (Na, Ca, P, Mg) concentrations
      showed no significant changes. However, the serum potassium concentration had
      decreased significantly at the onset of signs. The cerebrospinal fluid analyses
      revealed a significant increase in lactate and pyruvate concentrations and
      lactate/pyruvate ratio in amprolium-fed calves. The electrolytes (Na, K, Ca, P
      and Mg) of cerebrospinal fluid did not show any change. It is concluded that oral
      administration of amprolium (300 mg/kg body weight daily) for 4-6 weeks produces
      biochemical changes characteristic of polioencephalomalacia in buffalo calves.

PMID- 7817643
TI  - The development changes and correlations of some blood hormone levels and immune
      indexes during the postnatal period in neonatal calves.
AB  - The developmental changes and correlations of some hormone levels and immune
      parameters in six spontaneously delivered Holstein calves with a birth weight of
      40-50 kg were studied for a postnatal period of 1-15 days after birth. The mean
      levels of insulin (I), glucagon (Gc), cortisol (C) and growth hormone (GH) before
      feeding on day 1 were 9.68 +/- 3.27 muu/ml, 685.39 +/- 95.42 pg/ml, 14.27 +/-
      5.58 micrograms/dl and 0.85 +/- 0.10 ng/ml respectively. I and GH increased on
      day 2 and then decreased to a steady level. Gc and C fell fluctuantly within week
      1 and remained at a stable level after then. WBC, neutrophil percentage, B
      lymphocyte percentage, albumin percentage decreased with day of age in 1st week
      and lymphocyte percentage, T-lymphocyte percentage, T-G (total globulin)
      percentage and gamma-G percentage increased with day of age in 1st week and then
      reached a steady level. The correlations between some hormone levels and immune
      parameters indicated that C and Gc have significantly negative correlations with
      gamma-G (%), T-G (%) and T-lymphocyte (%) respectively. WBC is positively
      correlated to C and Gc significantly. The correlations of I and GH with some
      immune parameters have no significance.

PMID- 7817644
TI  - [The mechanisms of the restoration of motor activity following unilateral
      labyrinthectomy in the frog].

PMID- 7817645
TI  - [The Epstein-Barr virus contains DNA sequences highly homologous to many very
      important human genes and mRNA].

PMID- 7817646
TI  - [The characteristics of the properties of the membrane and cytosol peptidases of
      the enterocytes in different animal species].
AB  - Studies have been made on some of the properties of glycylleucyn- and
      leucylglycyne dipeptidases from the membrane and cytosol fractions of enterocytes
      of mice, rats and rabbits. Differences in cellular distribution of these enzymes
      in the species investigated were found. These enzymes also differ in their
      thermostability and the reaction to the effect of an inhibitor, 1,10
      phenantrolyne. Presumably, these peptidases are presented by different enzymes
      which are subjected to separate genetic control.

PMID- 7817647
TI  - [Introduction to the doctoral dissertation: "Conditioned reflexes through the
      eyes of the dog". 1908].

PMID- 7817648
TI  - [Subtypes of the functionally active muscarinic receptors in the heart of the
      frog Rana temporaria].
AB  - Radioligand analysis of ventricular membranes from the frog Rana temporaria with
      muscarinic antagonist 3H-QNB (qunuclidinul benzilate) revealed homogeneous
      population of highly specific muscarinic receptors with high affinity (Kd = 0.502
      +/- 0.020 nM and Bmax = 789 +/- 18 fmol/mg protein). Competitive binding of M1
      antagonist pirenzepine revealed two binding sites on the membrane with Kd values
      5.6 +/- 1.7 and 237 +/- 45 nM, and total capacity of 20.6 +/- 10.2 and 742 +/- 58
      fmol/mg protein respectively, which may be attributed to M1- and M2-subtypes in
      accordance with Receptor Nomenclature. The inhibitory effect of pirenzepine on
      negative inotropic action of Ach has been studied in the intact electrically
      stimulated ventricle. Analysis of the data by Schild procedure showed that KB for
      pirenzepine is equal to 13.9 +/- 2.4 nM. The results obtained suggest that the
      frog ventricle contains muscarinic cholinoreceptors of M2-subtype (possibly, M4
      subtype) which account for negative inotropic effect of Ach. Small population of
      M1-like receptors was also revealed, their functional role still remaining
      obscure.

PMID- 7817649
TI  - [The characteristics of the action on hydrobionts of the insecticide Valexon].
AB  - The effect of organophosphorus insecticide, valexon, has been investigated on
      hydrobionts from different taxonomic groups. Survival, locomotor activity, oxygen
      consumption and free radical spectra were determined. High sensitivity to the
      effect of the insecticide was found in Daphnia, due to the specific action of it
      on locomotor and respiratory functions, which are closely related in crustaceans.

PMID- 7817650
TI  - [The reaction of the chick embryo amnion to indolamines].
AB  - Studies have been made of the effect of serotonin and tryptamine on contractile
      activity of nerve-free smooth muscle strip from the amnion of 7-19-day chick
      embryos. It was shown that stimulatory effect of indolamines depends on the age
      of embryos. Within 7-9 days of incubation, there was a delay in the onset of the
      response, the sensitivity being rather low (threshold dose for serotonin-5
      microM); prolonged washing before each application of the drugs was usually
      necessary. At the 13-15th day, the reaction-becomes rather quick, being easily
      abolished by washing procedure; the sensitivity and the level of maximum reaction
      increase (for serotonin, mean Kd and Pmax values were equal to 0.3 microM and
      62.2 mg/mg tissue respectively). Developmental changes in responses to tryptamine
      are similar to those described for serotonin. The effectiveness of serotonin at
      the 7-9th day of incubation is significantly lower than that of Ach, whereas at
      the 13-15th day the value of Kd is similar to that for Ach, Pmax being often
      higher than for the latter. The data obtained are discussed in relation to
      proliferation changes in amniotic tissue.

PMID- 7817651
TI  - [The content of electrolytes (Na, K, Ca, Mg) in vertebrate otoliths and
      otoconia].
AB  - Na, K, Ca and Mg concentrations have been determined in the otoliths and otoconia
      of the lamprey, skate, guppy and hen. Lamprey otoliths sharply differ from the
      otoliths and otoconia of other animals with respect to their K and Ca content. In
      all the animals investigated excluding lamprey, only traces of K were found. Na
      concentration in the otilithic apparatus of the investigated animals varies
      within 0.475-1.04 mM/g. Na presumably is bound to proteins of the organic matrix
      and plays an important role in the growth of otoliths and otoconia. Concentration
      of Ca in the otoliths and otoconia of all animals excluding the lamprey was equal
      to 9.09-9.63 mM/g: organic substances constitute 4-10 per cent of their mass. In
      the lamprey, Ca concentration in the otoliths was found to be 5.33 mM/g, the
      content of organic matter amounting to more than 40 per cent. In constantly
      growing otoliths of fish, concentration of Mg was significantly lower than in
      otoconia of fish and other animals. This is presumably due to the fact that Mg
      inhibits crystalline growth of calcium salts.

PMID- 7817652
TI  - [The conformational aspects of the interaction of the cholinesterases of Pacific
      Ocean squid and vertebrates with derivatives of polymethylene
      bis(trimethylammonium)].
AB  - Conformational properties of a series of polymethylenebis (trimethylammonium)
      derivatives [formula: see text] (n = 4-10), cholinesterase reversible inhibitors,
      were studied by molecular mechanics method. Conformation-activity relationships
      between these inhibitors and human erythrocyte acetylcholinesterase, horse plasma
      butyrylcholinesterase, cholinesterases from the brain of the frog Rana temporaria
      and from visual ganglia of the squid Todarodes pacificus were investigated by
      correlational methods. Differences in mechanisms of antienzyme actions were
      determined.

PMID- 7817653
TI  - [A kinetic study of the blood serum cholinesterase activity in the freshwater
      fish Abramis ballerus].
AB  - In reaction of hydrolysis of choline and thiocholine esters of carbonic acids at
      25 degrees C, cholinesterase activity of the blood serum from the fish A.
      ballerus has been studied by modified Ellman's method and potentiometric
      titration method. The activity is maximal in pH region 7.5-9.0 and is not
      inhibited by high concentration of substrates. Michaelis constants and maximal
      rates for the enzyme reactions were determined. Butyrylcholine and
      butyrylthiocholine were hydrolyzed with the highest rates by the serum. Some of
      the organophosphorus inhibitors (diisopropylfluorphosphate and DDVF) inhibit
      cholinesterase activity of the blood serum significantly faster, whereas some of
      the carbamates (aminostygmin, eserine, etc.) inhibit it significantly slower than
      typical butyrylcholinesterase from horse blood serum and typical
      acetylcholinesterase of human erythrocytes. Besides, with respect to the
      sensitivity to inhibitors and some other properties, fish blood serum
      cholinesterase differs from other known cholinesterases.

PMID- 7817654
TI  - [The effect of urea on the activity of lactate dehydrogenase from the muscles of
      swine and skates].
AB  - Urea competitively inhibits the reduction of pyruvate by LDH from pig and skate
      muscles at pyruvate concentrations up to 1 mM, inhibition constant being equal to
      400-500 mM. It increased the value of Michaelis constant for pyruvate, activated
      both dehydrogenases with a maximum effect near 0.5-0.6 M. The level of activation
      of LDH from pig muscles was rather stable amounting to 10-20%, whereas it
      increased for the enzyme of the skate with the increase of pyruvate concentration
      up to 30 mM. Similarly, although less effectively, both dehydrogenases were
      activated by KCl solutions.

PMID- 7817655
TI  - [The distribution of aspartate aminotransferase activity in the structures of the
      visual analyzer in the canine brain during postnatal ontogeny].
AB  - Studies have been made on aspartate aminotransferase activity in light and heavy
      synaptosomes, membrane and synaptic mitochondria from the visual cortex (field
      17), bigeminal bodies, and outer geniculate body. It was shown that the enzymic
      activity significantly decreases in all the subfractions investigated in puppies
      beginning from 6 months up to 1 year. In earlier postnatal ontogenesis, the
      activity increased in all the subfractions, the extent of the increase being
      dependent on the source of the enzyme.

PMID- 7817656
TI  - [2 stages in the development of spontaneous motor activity in the early postnatal
      ontogeny of rats].
AB  - In ontogenesis of rats, similar to many other animals, in the development of the
      spontaneous motor activity two qualitatively different stages are observed. The
      first one is characterized by periodic, mainly sensor-independent generalized
      motor excitation which at the second stage is substituted by stereotypic
      specialized motor programs (locomotion, grooming). Both stages exhibit similar
      age dynamics: the increase in the activity, its maximum and subsequent inhibition
      with a shift of the corresponding phases for about two weeks. This dynamics is
      mainly associated with heterochronous maturation of excitatory and inhibitory
      systems of regulation of the nervous activity. Change in the stages depends on
      changes of functional role of motor activity in ontogenesis from mainly
      morphogenetic one (and promotion of a necessary level of vegetative functions) to
      directional behavior. Inhibition at the first stage results in deep functional
      rearrangement in the central nervous system serving as a background for the onset
      of specialized behavioural activity. The development of the latter is also
      excessive, the subsequent inhibition being less deep and reversible.

PMID- 7817657
TI  - [The possible mechanisms of the participation of the central cholinoreactive
      systems in regulating spontaneous motor activity in the early ontogeny of rats].
AB  - In experiments on 0-16-day rat puppies, studies have been made of the effects of
      activation of N-cholinoreceptors during injections of nicotine, inactivation of N
      cholinoreceptors by ganglerone, as well as combination of ganglerone and DOPA on
      the spontaneous periodic motor activity. It was shown that activation of N
      cholinoreceptors results in the reactions which were earlier described for
      newborn rats during injection of exogenous catecholamines, i.e. the increase in
      motor activity and the onset of rhythmic components in the latter. Experiments
      with spinalization and DOPA injection showed that the potentiating effect of
      nicotine is realized via the descending catecholaminergic systems. Therefore,
      central N-cholinoreactive systems are mature already in newborn animals
      exhibiting from the very first day of postnatal life modulatory effects on
      catecholaminergic neurones in the brain stem.

PMID- 7817658
TI  - [Neophobia in rats during the transition from milk to definitive nutrition].
AB  - After isolation of rat puppies from mother at the age of 17, 21, 26, 31 or 36
      days, studies have been made within 3 days on water consumption and utilization
      of a 0.2% solution of saccharin. The presence or absence of neophobia were
      indicated by relative consumption of saccharin solution in percentage to total
      volume of drinking. It was shown that at the age of 17-19 days neophobia is
      absent, at 21-23 days it becomes evident, at 26-28 days it is present only in
      females, at 31-33 days it is absent in animals of both sexes (saccharin
      consumption at this age is maximal), at 36-38 days significant neophobia was
      registered both in females and males. Fluctuations in neophobia are discussed in
      relation to weanling.

PMID- 7817659
TI  - [Ectacytometry of the erythrocytes in rats of the SHR, WKY and Wistar strains].
AB  - Deformation properties of erythrocytes have been studied using osmotic gradient
      ectacytometric procedure in rats with spontaneous hereditary hypertension (SHR),
      normal tension rats from Wistar-Kyoto strain and albino rats from Wistar strain.
      It was shown that high intrinsic viscosity and, to a less extent, changes in
      their form account for the increased rigidity of the erythrocytes from SHR rats.
      No significant changes in visco-elastic properties of the membrane were found.
      The degree of hydration of haemoglobin significantly increases in the order SHR
      WKY-Wistar.

PMID- 7817660
TI  - [The characteristics of the forms of perceptive and cognitive activities in
      adolescent chimpanzees].
AB  - The study of cognitive activity in four 4-6-year-old chimpanzees was carried out
      during visual their discriminating and summarizing of signals (pictures of
      natural objects and volume figures). It was established that apes were able to
      compare the signals according to their size. Chimpanzees were successful in
      transferring their experience from one image type to another. The data obtained
      proof that apes were able to summarize, operate with abstract ideas and think
      logically.

PMID- 7817661
TI  - [The structural organization of the sensorimotor cortex in the Baikal seal Pusa
      sibirica].

PMID- 7817662
TI  - [The evolution of the nonapeptidergic neurosecretory formations of the
      hypothalamus in vertebrate animals].

PMID- 7817663
TI  - [Serotonin receptors participating in the modulation of the adenylate cyclase
      system in the tissues of vertebrates and invertebrates].

PMID- 7817664
TI  - [DSIP: the sleep peptide or an unknown hypothalamic hormone?].

PMID- 7817665
TI  - Analysis of beta-glucocerebrosidase and ceramidase activities in atopic and aged
      dry skin.
AB  - To elucidate the mechanisms that are involved in the decrease of ceramide levels
      in atopic dry skin and in aged skin, we examined both the activities of beta
      glucocerebrosidase, which is a major enzyme in ceramide production, and of
      ceramidase, which is an essential enzyme in ceramide degradation, in the stratum
      corneum of atopic dry skin and aged skin. The specimens of the stratum corneum of
      forearm skin were obtained by tape-stripping from 61 healthy volunteers and 23
      patients with atopic uninvolved skin. The beta-glucocerebrosidase activity in the
      stratum corneum extracts was estimated using fluorescent 4-methylumbelliferyl
      beta-D-glucopyranoside as the substrate. Ceramidase activity was determined using
      14C-palmitoylsphingosine as the substrate. Among the atopic skin samples, neither
      beta-glucocerebrosidase nor ceramidase activities were different from those of
      age-matched healthy controls. Nor was the beta-glucocerebrosidase activity
      deficient in the aged skin samples as compared to that seen in samples from the
      young, healthy group. In contrast, there was an age-related upregulation in
      ceramidase activity. The results indicate that the decrease of ceramides in
      atopic dry skin may not be accompanied by reduced synthesis or by enhanced
      degradation, each of which is primarily attributable to the above two enzymes,
      respectively. The pathogenesis of aged dry skin can be explained, at least
      partially, in terms of elevated ceramidase activity, which results in a
      disturbance of the lamellar structure of the stratum corneum lipids.

PMID- 7817666
TI  - Cross-reactivity to metal compounds studied in guinea pigs induced with chromate
      or cobalt.
AB  - Multiple sensitivity to metals is often seen in humans. This may be due to cross
      reactivity or to multiple sensitization. The pattern of cross-reactivity to some
      metal compounds was studied, using the guinea pig maximization test method.
      Animals were induced with K2Cr2O7 and CoCl2, respectively, and then challenged
      with K2Cr2O7, CoCl2, NiSO4, PdCl2 and RhCl3. No simultaneous reactivity was
      recorded. This supports the view that simultaneous reactivity in patients to
      nickel-cobalt and to chromate-cobalt is due to multiple exposure and
      sensitization, and not to cross-reactivity. The purity of the test compounds was
      analysed.

PMID- 7817667
TI  - An immunohistochemical study of lysozyme in the skin of psoriatic patients.
AB  - The distribution of lysozyme was investigated in psoriatic skin lesions,
      perilesional skin and in skin from healthy controls, using the immunoperoxidase
      techniques avidin-biotin complex and alkaline phosphatase-anti alkaline
      phosphatase. Lysozyme was identified in polymorphonuclear leukocytes present in
      the Munro microabscesses and also occasionally in other parts of the skin, as
      shown by very strong cytoplasmic staining. Stratum corneum, stratum granulosum
      and stratum spinosum were weakly stained. In some cases positive staining along
      the dermal collagen bundles was demonstrated and is most likely to be related to
      the number of inflammatory cells in the papillary dermis. Psoriatic skin lesions
      stained significantly stronger for lysozyme than did perilesional skin (p <
      0.0001), whereas skin from healthy controls stained weakly positive or was
      lysozyme negative. Lysozyme may be of some importance in the psoriatic disease
      process. By comparison the alkaline phosphatase-anti-alkaline phosphatase was
      found to be the most specific of the two techniques.

PMID- 7817668
TI  - Dicarboxylic acids affect the growth of dermatophytes in vitro.
AB  - Azelaic acid is a dicarboxylic acid with known antimycotic activity. In this
      study we have used an agar dilution technique to test the effect of six other
      dicarboxylic acids (sebacic, undecanedioic, dodecanedioic, tridecanedioic,
      tetradecanedioic and hexadecanedioic acid, 10(-4)-10(-2) mol/l, pH 5.5) on in
      vitro growth of Trichophyton (T.) rubrum, T. mentagrophytes and Microsporum (M.)
      canis. Furthermore, the fungicidal activity of 10(-2) mol/l undecanedioic and
      sebacic acid was tested using a T. rubrum growth assay. Undecanedioic acid proved
      fungistatic at 10(-2) mol/l for all species and fungicidal for T. rubrum. A minor
      fungistatic effect on T. rubrum and T. mentagrophytes was also seen with the
      other acids at this concentration. M. canis was inhibited only by high
      concentrations of four acids, whereas low concentrations of all six agents
      resulted in enlarged thallus diameters. We conclude that among dicarboxylic acids
      fungistatic activity is not limited to azelaic acid. Undecanedioic acid appears
      promising for further investigations.

PMID- 7817669
TI  - Evidence for a complement-mediated inhibition and an antibody-dependent cellular
      cytotoxicity of dermal fibroblasts in alopecia areata.
AB  - Immunological mechanisms have long been suggested to mediate hair loss in
      alopecia areata. In this process hair bulb melanocytes and dermal papilla
      fibroblasts are believed to be primarily involved. In the present study we
      further investigated the role of humoral factors in alopecia areata. Three
      different experiments were performed on normal human epidermal melanocytes as
      well as normal human dermal fibroblasts: (i) incubation with medium containing 2,
      10, or 20% alopecia areata serum (n = 12 patients) for 16 h, (ii) incubation with
      medium supplemented with preheated alopecia areata serum (1 h at 56 degrees C)
      and healthy human fresh serum as a complement source (1:1) and (iii) incubation
      with 2, 10 or 20% alopecia areata serum but, in addition, containing peripheral
      blood mononuclear cells from healthy subjects (effector/target ratio, 50:1). As
      controls, normal human fibroblasts and normal human epidermal melanocyte cultures
      were also incubated with serum from healthy individuals (n = 5) under the same
      culture conditions. The results showed that alopecia areata serum exerted a
      significant stimulation of proliferation of both normal human fibroblasts (p >
      0.05 at 2%, p > 0.05 at 10%, p < 0.05 at 20%), and normal human epidermal
      melanocytes (p > 0.05 at 2%, p < 0.05 at 10%, p > 0.05 at 20%).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7817670
TI  - Presence of Epstein-Barr virus in cutaneous lesions of mycosis fungoides and
      Sezary syndrome.
AB  - It has been suggested that prolonged antigenic stimulation contributes to the
      development of epidermotropic cutaneous T cell lymphoma (CTCL), mycosis fungoides
      and Sezary syndrome, characterized by a cutaneous infiltration of proliferating
      helper T cells. Since Epstein-Barr virus (EBV) antibodies were increased in CTCL
      sera, we investigated a possible etiologic role for EBV in epidermotropic CTCL by
      looking for the EBV genome in 25 cutaneous biopsies of mycosis fungoides or
      Sezary syndrome and 12 reactional inflammatory skin lesions. The use of a non
      isotopic in situ hybridization procedure based on the detection of Epstein-Barr
      encoded RNAs with biotinylated oligonucleotide probes (EBER) revealed 32% of the
      lesions with CTCL to be positive for EBV (3 in dermis, 3 in epidermis, 2 both in
      dermis and epidermis), as compared to no detection of the EBV genome in the
      reactional inflammatory skin lesions. Moreover, a combined hybridization (EBER
      probe) and immunochemistry technique (anti-CD3 or anti-Kil monoclonal antibody)
      permitted the identification of EBV in T cells of dermis and in keratinocytes,
      respectively. The identification of EBV in epidermotropic CTCL suggests that this
      virus could play a role in the development of these CTCLs, either as an
      etiological agent or more probably as a chronic activating agent. Indeed, the
      infection of keratinocytes by EBV could activate them and so induce the
      production of in situ cytokines (IL1a, IL6, TNFa) playing a role in the
      development of tumoral infiltrate.

PMID- 7817671
TI  - A DNA-flow cytometric analysis of trichilemmal carcinoma, proliferating
      trichilemmal cyst and trichilemmal cyst.
AB  - DNA-flow cytometric analyses were performed on paraffin-embedded sections of
      trichilemmal carcinoma, proliferating trichilemmal cyst, and trichilemmal cyst.
      Nine out of 10 cases of trichilemmal carcinoma and 2 out of 5 cases of
      proliferating trichilemmal cyst showed aneuploidy. No aneuploidy was detected in
      6 cases of benign trichilemmal cyst. The proliferating index (percentage of cells
      that exceeded the diploid peak (G0/G1) plus 4 standard deviations) of
      trichilemmal carcinoma, proliferating trichilemmal cyst, and trichilemmal cysts
      was 43.5 +/- 3.8%, 32.5 +/- 7.5%, and 23.1 +/- 2.0%, respectively. In one out of
      the 6 cases of trichilemmal carcinoma that were large enough for us to
      investigate regional differences, DNA ploidy heterogeneity was detected. The
      incidence of aneuploidy of trichilemmal carcinoma was significantly higher than
      that of squamous cell carcinoma (14%), previously described by us using the same
      method.

PMID- 7817673
TI  - Interleukin 1 alpha (IL-1 alpha) in human skin in vivo: lack of correlation to
      markers of collagen metabolism.
AB  - Levels of interleukin 1 alpha (IL-1 alpha) were studied from blister fluids
      collected from 14 patients with various types of blistering diseases. In all the
      fluids, IL-1 alpha could be detected, the concentrations varying from 5 to 1730
      pg/ml. For comparison IL-1 alpha was also assayed from suction blisters of 13
      subjects; 8 atopic patients and 5 healthy controls. IL-1 alpha was also present
      in suction blisters in measurable quantities, suggesting that during suction IL-1
      alpha is released into the blister cavity. Since IL-1 alpha has been shown to
      have marked effects on collagen metabolism, the marker of collagen synthesis
      (carboxyterminal propeptide of type I procollagen (PICP)) and gelatinase were
      assayed from the same samples. There was no apparent correlation between the
      levels of IL-1 alpha, PICP or gelatinase in blister fluids. The possible
      association of IL-1 alpha and collagen metabolism was further studied in
      experimental conditions. Topical glucocorticoid markedly decreased the level of
      PICP in suction blisters but did not have any significant effect on IL-1 alpha.
      UVB-radiation, on the other hand, caused increase in IL-1 alpha but did not have
      any profound effect on collagen metabolism. During the re-epithelialization of
      the blister floor the level of IL-1 alpha decreased markedly, and at the same
      time the expression of gelatinase was increased. The results indicate that IL-1
      alpha is released in large quantities into blister fluid when using the suction
      blister model. However, no apparent correlation could be observed in healthy or
      diseased skin between the levels of IL-1 alpha, collagen synthesis marker or
      gelatinase.

PMID- 7817672
TI  - Helicobacter pylori in patients with systemic sclerosis: detection with the 13C
      urea breath test and eradication.
AB  - In patients with systemic sclerosis peristaltic abnormalities may delay gastric
      emptying, giving rise to bacterial overgrowth, including possibly Helicobacter
      pylori (HP). Infection with Helicobacter is an important risk factor for
      esophageal and gastric diseases, including esophagitis, gastritis and gastric
      cancer. The purpose of this prospective study was to assess gastric HP infection
      in patients with systemic sclerosis. In 12 patients with systemic sclerosis the
      newly introduced breath test with 13C-labelled urea was used for indirect
      detection of gastric urease activity due to HP infection. Five out of 12 patients
      gave Helicobacter-positive results (42%); 7 patients were negative for
      Helicobacter colonization (58%). Thus, the risk for gastric diseases caused by HP
      infection is enhanced in patients with systemic sclerosis compared with white
      healthy, asymptomatic persons examined in other studies. Helicobacter-positive
      patients were treated with 2 x 20 mg omeprazole and 4 x 500 mg amoxicillin over
      14 days. Afterwards the 13C-urea breath test was repeated and showed negative
      results for Helicobacter in all systemic sclerosis patients treated. Dual therapy
      with omeprazole and amoxicillin therapy effectively eradicated HP. The 13C-urea
      breath test did not cause any side-effects and is therefore considered to be a
      non-invasive, non-toxic and safe method for the diagnosis and therapeutic control
      of Helicobacter-status.

PMID- 7817674
TI  - Plasma endothelin and the aminoterminal propeptide of type III procollagen
      (PIIINP) in systemic sclerosis.
AB  - Forty-four patients with systemic sclerosis and 3 patients with localized
      scleroderma were investigated for plasma endothelin and aminoterminal propeptide
      of type III procollagen (PIIINP). Although there was an overlap between plasma
      levels of endothelin in patients with systemic sclerosis and healthy controls,
      the mean value of the patients was significantly higher than in controls. Plasma
      endothelin was normal in all 3 patients with localized scleroderma. The highest
      levels of plasma endothelin were found in patients with type II and III systemic
      sclerosis with the largest cutaneous involvement, and in patients with the
      scleroderma-specific antibodies Scl-70 and anticentromere antibodies. Extremely
      high values were found in a patient who experienced a renal crisis and in a
      patient who had her lower leg amputated due to severe vasculitis. A positive
      correlation was found between plasma endothelin and serum PIIINP. This, together
      with the fact that in systemic sclerosis the vascular lesions are the earliest,
      would seem to support the theory that endothelial cell damage could lead to
      increased secretion of endothelin and subsequent fibrosis in this disease.

PMID- 7817675
TI  - Allergic and irritant contact responses to DNFB in BN and LEW rat strains with
      different TH1/TH2 profiles.
AB  - BN and LEW rats possess different and extreme profiles of TH1/TH2 cells. The main
      objective of this study was to determine if this constitutively expressed
      property may influence the propensity to develop contact allergy to a potent
      contact sensitizer, 2,4-dinitro-1-fluorobenzene (DNFB). In order to avoid
      overlapping reactions due to toxicity, we defined non-irritant threshold levels
      of DNFB histologically in ear skin, dorsal skin and oral mucosa prior to the
      sensitization experiments. Evaluation of the elicitation response was carried out
      by an invasive method (biopsy). LEW rats proved to express a more extensive
      challenge response to DNFB than rats of the BN strain. Further, epicutaneous
      sensitization with DNFB gave a better challenge response than the subcutaneous
      route regardless of rat strain. In ear skin, but not in oral mucosa, the response
      was more vigorous after five than after two exposures. Our results are discussed
      with respect to the possibility that the TH1 type cells may play a significant
      role in the development of experimental contact allergy.

PMID- 7817676
TI  - In vivo studies concerning a pH gradient in human stratum corneum and upper
      epidermis.
AB  - Human skin has an acid mantle of pH 4-6, contrasting with the almost neutral pH
      of the interior body and implying the existence of a pH gradient over the horny
      layer that might influence a variety of epidermal processes. In an attempt to
      characterize the pH gradient, we applied a glass electrode to the volar surface
      of the forearm before and after consecutive strippings with sello-tape. Before
      stripping, the surface pH (mean +/- SD) was 4.5 +/- 0.2 in men (n = 7) and 5.3 +/
      0.5 in women (n = 7), the values gradually increasing to pH 6.9 +/- 0.4 in men
      and 6.8 +/- 0.5 in women after about 100-120 tape strippings, which completely
      removed the stratum corneum. When plotted against the number of strippings, the
      pH values usually conformed to a sigmoid curve with inflection (50% change) after
      about 60 strippings, at a level corresponding histologically to the lower third
      of stratum corneum. Similar gradients were found also in skin of the abdomen and
      calf. Stripping with cyanoacrylate resin produced a similar gradient, even though
      this form of stripping was 10 times more effective. The healing process after
      tape stripping was studied by determining pH and transepidermal water loss in 5
      persons over a period of 14 days. The importance of the re-established pH
      gradient is discussed in relation to the many pH-dependent enzymes operating in
      stratum corneum.

PMID- 7817677
TI  - Dermatitis with an unusual explanation in a welder.
AB  - Occupational diseases among welders include asthma, acute keratoconjunctivitis,
      and various skin disorders. A localized cutaneous erythema from UVC radiation is
      common and does not generally constitute any problem, as its cause is obvious to
      the welder, the symptoms are slight, and it is transient. In this report a welder
      with UVC-induced erythema on the cheeks is described. Initially, neither the
      worker, the physician at the factory, nor ourselves suspected a UVC erythema.
      Extensive investigations, including factor visits with measurements of UVA, UVB,
      and UVC irradiance during welding, revealed the cause of the dermatitis to be
      UVC, most likely reflected from a textile hood used to prevent exposure to dirt.

PMID- 7817678
TI  - Nickel patch test reactivity and the menstrual cycle.
AB  - Premenstrual exacerbation of allergic contact dermatitis and varying allergic
      patch test responses have been reported at different points of the period. Using
      a dilution series of nickel sulphate, we studied the variation in patch test
      reactivity in nickel allergic women in relation to the menstrual cycle. Twenty
      women with regular periods were tested on day 7-10 and on day 20-24. Ten nickel
      patch tests with different concentrations were applied using the TRUE test assay,
      and the threshold concentration of nickel sulphate eliciting an erythematous
      reaction was determined. Half of the women were tested first on day 7-10 and the
      other half first on day 20-24. There was no difference in the degree of patch
      test reactivity, when the results from day 7-10 and day 20-24 were compared (p >
      0.4). However, when we compared the patch test results from the first and second
      test procedure, we found an increased nickel sensitivity at the second patch test
      (0.02 < p < 0.05), suggesting a booster effect from the first patch test
      procedure. In conclusion, we could not demonstrate an increased sensitivity to
      nickel sulphate patch tests premenstrually in 20 nickel allergic women, but we
      found that elicitation of positive patch tests led to an increased skin
      reactivity towards the same allergen, when the patients were retested weeks
      later.

PMID- 7817679
TI  - Familial pachydermodactyly.
AB  - Pachydermodactyly is a rare form of digital fibromatosis. There are only 15 cases
      reported in the literature, all with a negative family history. Only one of the
      previously reported cases was a woman. We now report 2 female cases, mother and
      daughter, who, to the best of our knowledge, are the first patients with familial
      pachydermodactyly. The histological evolution of this disease over the years had
      not been previously reported.

PMID- 7817680
TI  - POEMS syndrome and multiple angioproliferative lesions mimicking generalized
      histiocytomas.
AB  - A case of POEMS syndrome and Castleman's multicentric disease is reported.
      Multiple long-standing cutaneous lesions, histologically similar to
      histiocytomas, were the initial manifestation of POEMS syndrome. A high incidence
      of angiomatous lesions associated with POEMS syndrome has already been
      established. To our knowledge, this report is the first report to associate
      multiple angioproliferative lesions mimicking generalized histiocytomas with
      POEMS syndrome.

PMID- 7817681
TI  - Toxic epidermal necrolysis and erythema multiforme following therapy with
      terbinafine.
AB  - We report two cases with severe skin reactions following oral terbinafine
      (Lamisil) therapy. The first case was a 49-year-old woman with onychomycosis of
      the toe nails. She had suffered from diabetes for 3 years, but it was well
      controlled on insulin. Five days after start of terbinafine 250 mg once daily she
      developed erythema. The treatment was continued for 2 days, but the skin eruption
      progressed, and a clinical diagnosis of toxic epidermal necrolysis was confirmed
      histologically. The second case was a 51-year-old woman with dermatomycosis on
      the right foot. She developed a papular eruption in the second week after taking
      terbinafine 250 mg once daily. Despite this eruption she continued treatment for
      6 days. Generalized erythema multiforme developed in the following days.
      Terbinafine is a recently introduced efficacious fungicidal drug. This is the
      first report of toxic epidermal necrolysis following terbinafine.

PMID- 7817682
TI  - Polymerase chain reaction for monitoring human papillomavirus contamination of
      medical personnel during treatment of genital warts with CO2 laser and
      electrocoagulation.
AB  - Genital warts and intraepithelial neoplasia caused by infection with human
      papillomavirus are usually treated with CO2 laser or electrocoagulation. In this
      study, contamination of personnel and operating theatres with human
      papillomavirus DNA during treatment sessions was investigated. Samples were taken
      from the nostrils, nasolabial folds and conjunctiva of the operating physician
      before and after operating sessions and from Petri dishes left open in the
      operating theatres. Human papillomavirus DNA was demonstrated by the polymerase
      chain reaction technique. The results show that there is a risk of contamination
      of the operator by human papillomavirus DNA, detectable with the polymerase chain
      reaction technique, during both CO2 laser and electrocoagulation treatment.

PMID- 7817683
TI  - Giant spontaneous hematoma of the thoracic wall in a patient with REST syndrome.
AB  - We report on a 56-year-old patient with systemic sclerosis of one and a half
      year's duration who was admitted with an acute soft tissue swelling over the left
      scapula and a marked reduction of joint mobility of the left shoulder. Over the
      following days, the swelling extended distally and a hemorrhagic discoloration
      developed, reaching down to the scrotum. Nuclear magnetic resonance imaging
      revealed a giant intermuscular hematoma between the serratus anterior and the
      costal muscles. This is the first report of an extensive spontaneous hematoma of
      the thoracic wall in a patient with progressive systemic sclerosis. Its
      development and unusual localization may be explained by both the underlying
      systemic sclerosis and the patient's previous profession as a trapeze artist.
      Hemorrhagic complications of systemic sclerosis are rare but should be watched
      for in these patients.

PMID- 7817684
TI  - Efficacy and safety of the 20-epi-vitamin D3 analogue KH 1060 in the topical
      therapy of psoriasis: results of a dose-ranging study.
AB  - KH 1060 is a 20-epi-vitamin D3 analogue, structurally related to 1,25
      dihydroxyvitamin D3 (1,25(OH)2D3). In vitro, KH 1060 is much more potent than
      1,25(OH)2D3 in regulating cell growth and T lymphocyte mediated immune responses,
      despite a similar calcemic activity in vivo. Therefore, KH 1060 is of potential
      interest in the treatment of psoriasis and other diseases characterized by
      accelerated cell growth and T lymphocyte activation. In a multicenter,
      prospective, randomized, double-blind, vehicle-controlled right/left comparative
      study, patients with plaque-type psoriasis vulgaris were randomly assigned to one
      of the following treatment groups: (I) KH 1060 ointment 0.2 microgram/g versus
      placebo ointment, (II) KH 1060 ointment 0.2 microgram/g versus KH 1060 ointment
      0.04 microgram/g, and (III) KH 1060 ointment 0.2 microgram/g versus KH 1060
      ointment 1 microgram/g. All treatments were given twice daily for 6 weeks. Sixty
      four of the 70 randomized patients completed the study. At the end of treatment,
      no difference was demonstrated between KH 1060 0.04 microgram/g and vehicle,
      whereas significantly increasing improvement was found for the doses KH 1060 0.2
      microgram/g and KH 1060 1 microgram/g. According to the investigator's overall
      assessments at the end of treatment, KH 1060 1.0 microgram/g and KH 1060 0.2
      microgram/g produced a marked or moderate improvement in most patients. Mild
      lesional irritation was observed after treatment with KH 1060 as well as with
      placebo. One patient was withdrawn because of an eczematous reaction, where KH
      1060 1.0 microgram/g was applied.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7817685
TI  - Plantar Trichophyton rubrum infections may cause dermatophytids on the hands.
AB  - Over a 2-year period, we saw 37 patients with a diagnosis of dermatophytid on the
      hands based on 1) culture-proven dermatophytosis on one or both feet; 2)
      symmetrical, secondary vesicular eruptions on the fingers and/or palmar aspects
      of the hands; and 3) a resolution in both areas of involvement after treatment of
      the dermatophytosis on the foot. During the study period, 128 patients had
      culture-proven dermatophytosis of the feet caused by Trichophyton rubrum. Nine of
      these (7%) developed dermatophytid. Seventy-eight patients had dermatophytosis of
      the feet caused by Trichophyton mentagrophytes. Twenty-seven of these (35%)
      developed dermatophytid. One of 6 patients infected on the feet with
      Epidermophyton floccosum developed dermatophytid.

PMID- 7817686
TI  - Simulation of solar lentigo by spreading pigmented actinic keratosis.

PMID- 7817687
TI  - Papular-purpuric gloves and socks syndrome.

PMID- 7817688
TI  - "Bee sting therapy": the revival of a dangerous practice.

PMID- 7817689
TI  - Acral persistent papular mucinosis (APPM) with pruritus. A case report and mast
      cell quantification.

PMID- 7817690
TI  - Penile cancer associated with an artificial penile nodule.

PMID- 7817691
TI  - Comparison of methods for recording esophageal sphincter pressures in Chagas'
      disease.
AB  - We measured the lower (LES) and upper esophageal sphincter (UES) pressure in 22
      Chagas' disease patients with dysphagia and abnormal radiologic esophageal
      examination, and in 12 normal volunteers. We compared the station pull-through
      (SPT) and rapid-through (RPT) techniques of sphincter pressure measurement, using
      an infused round catheter 5 mm in outer diameter, and with four side orifices at
      the same level. The LES pressure was higher when measured by RPT than by SPT and
      at inspiration than expiration (P/0.05). In Chagas' disease patients, LES
      pressure was lower than in volunteers, with significance when measured by RPT at
      expiration (P/0.05). In normal volunteers, but not in patients, the UES pressure
      was higher when measured by RPT at expiration than when measured by SPT. When
      measured by RPT the UES pressure of Chagas' disease patients was lower than in
      volunteers. In conclusion, LES pressure was higher when measured at inspiration
      and by the RPT technique. There was a considerable overlap of LES individual
      pressures between patients and volunteers, but the pressure was lower in patients
      when we used RPT at expiration. In normal volunteers the RPT technique recorded
      higher UES pressures than the SPT, and higher pressures than in Chagas' disease
      patients.

PMID- 7817692
TI  - [Emergency panendoscopy in children with upper digestive bleeding. Diagnostic and
      therapeutic value].
AB  - The aim of this paper was to review the current concepts in the early diagnosis
      of the upper gastrointestinal bleeding by emergency endoscopy, its value in
      ulcers and the factors predicting poor outcome. Variceal bleeding from the
      esophagus as a complication of portal hypertension is also reviewed. The
      expanding role of endoscopy for gastrointestinal hemorrhage is emphasized.

PMID- 7817693
TI  - [Beneficial effects of fermented milk on the intestine].

PMID- 7817695
TI  - [Expansible prosthesis of the bile ducts, initial experience].

PMID- 7817694
TI  - [Sporadic hepatitis C: an unresolved enigma].

PMID- 7817696
TI  - Prevalence of hepatitis C in health care workers investigated by 2nd generation
      enzyme-linked and line immunoassays.
AB  - The aim of this study was to evaluate the prevalence of antibodies to hepatitis C
      virus (anti-HCV) in health-care workers (HCW). Sera from 439 unselected HCW were
      assessed for anti-HCV by 2nd generation enzyme-linked immunoassay (ELISA) and
      anti-HBc by ELISA. Anti-HCV (+) sera were evaluated by line immunoassay (LIA)
      (LiaTeK, Organon). Anti-HCV proved positive by ELISA in 12 (2.73%) subjects, 6 of
      whom were reactive by LIA, one was indeterminate and 5 non reactive. The
      prevalence of anti-HCV confirmed by LIA was 1.59% (7 subjects). Positive anti-HCV
      results with an ELISA ratio greater than 3 were LIA reactive in 6/6 as compared
      with 5 LIA non reactive with an ELISA ratio less than 2, while in the
      indeterminate serum the ratio was 2.5. No differences in age, profession,
      seniority, history of hepatitis or transfusions were found between anti-HCV (+)
      and (-) subjects, but females predominate significantly. The areas of higher risk
      were hemodialysis, obstetrics, surgery and intensive care. Anti-HBc was (+) in
      85.7% (6/7) of the anti-HCV (+) subjects. Follow-up of anti-HCV (+) subjects
      showed raised alaninoaminotransferase levels in 4 cases, while liver biopsies in
      3 disclosed cirrhosis, chronic active hepatitis and chronic persistent hepatitis.
      The anti-HCV prevalence in HCW is low compared with other risk groups perhaps due
      to the peculiar epidemiological features of HCV. In low risk groups for HCV
      infection a positive ELISA result with a ratio lower than 3 should be confirmed
      by more specific tests.

PMID- 7817698
TI  - [Psychological differences between ulcer and non-ulcer dyspeptic patients].
AB  - The existence of differences in the psychological profile of 39 endoscopically
      evaluated patients with ulcer (U) and non ulcer (NU) dyspepsia were examined.
      There were 21 U and 18 NU subjects. Cigarette smoking, intake of alcohol, coffee,
      mate, aspirin and NSAID were recorded, but there were no significant differences
      between the two groups. Personality traits were determined by the Rorschach Test,
      considering psychological profile (introversive, extroversive, self-restrained),
      impulse and emotion control (do not allow their expression, impulsive, adequately
      conveyed) and level of social adaptation (low, normal, high). U and NU subjects
      experienced a similar number of potentially stressful life events. However, U
      patients perceived their events more negatively. Although no one type of "ulcer
      personality" was found consistently, ulcer patients tended to be more
      introversive and they had a better social adaptation than NU.

PMID- 7817697
TI  - Serum gastrin, pepsinogens, parietal cell and Helicobacter pylori antibodies in
      patients with gastric polyps.
AB  - OBJECTIVES: To determine serum concentration of gastrin and pepsinogens (PGs) as
      markers for the gastric mucosal status and to elucidate the prevalence of serum
      Helicobacter pylori (H pylori) IgG antibodies and parietal cell autoantibodies
      (PCAs) in patients with gastric polyps. METHODS: The subjects in this study were
      composed of 36 patients with fundic glandular polyps (FGP), 25 patients with
      foveolar hyperplastic polyps (FHP), and 27 asymptomatic healthy volunteers
      (controls). Serum concentrations of gastrin and PGs were determined by
      radioinmmunoassay. H. pylori IgG antibodies were measured through an enzyme
      linked immunosorbent assay. PCAs were detected by an indirect immunofluorescence
      technique using cryostat sections of rat gastric mucosa. RESULTS: There were no
      significant differences between FGP patients and controls in serum concentrations
      of gastrin, PG I and PG II. FHP patients showed significantly higher serum
      gastrin, lower PG I, higher PG II levels and, as a consequence, far lower PG I/PG
      II ratio compared with controls. The prevalence of H pylori infection was much
      higher in FHP patients (84.0%), whereas lower in FGP patients (19.44%) than that
      in controls (40.7%) was positive in 24.0% of FHP patients, 2.78% of FGP patients
      and 4% of controls. CONCLUSIONS: These results suggest that FHP often develops in
      a gastric mucosa associated with H pylori infection, while FGP does not appear to
      be related to H pylori infection.

PMID- 7817699
TI  - Gastric mucosal protection by acetazolamide in rats. Roles of prostaglandins,
      sulfhydryls, and gastric motility.
AB  - The aim of this study was to test the hypothesis that protective effect of
      subcutaneous acetazolamide, a carbonic anhydrase inhibitor, against ethanol
      induced gastric mucosal damage is dependent on indomethacin- or iodoacetamide
      sensitive mechanisms. In addition we studied the effects of acetazolamide on
      gastric motility and the influence of indomethacin and iodoacetamide on this
      parameter. Indomethacin (30 mg/kg) or iodoacetamide (100 ag/kg) was administered
      subcutaneously in doses that previously had been demonstrated to inhibit
      endogenous prostaglandins synthesis and gastric mucosal sulfhydryls respectively.
      At 30 min after these or control subcutaneous pretreatment, the rats were given
      subcutaneous acetazolamide or vehicle. Thirty min later 96% ethanol was
      administered orally and the rats were sacrificed 60 min after ethanol
      administration. The lesions of the gastric glandular mucosa were measured in
      length and width and expressed in square millimeters. Gastric motility was
      recorded by a balloon method. The results showed that neither indomethacin nor
      iodoacetamide aggravated ethanol-induced gastric mucosal damage. The protective
      effect of subcutaneous acetazolamide was suppressed by pretreatment with
      indomethacin but not with that of iodoacetamide. Acetazolamide inhibited gastric
      motility in a dose-dependent fashion. The inhibited gastric motility induced by
      acetazolamide was reversed by indomethacin but not by iodoacetamide. A highly
      significant relationship was found between the inhibitory effect of acetazolamide
      on the motor activity and the mucosal lesions (r +/- 0.8777, P < 0.01). We
      conclude that the mechanism mediating subcutaneous acetazolamide protection
      against 96% ethanolinduced gastric mucosal lesions is dependent on indomethacin-
      and independent of iodoacetamide sensitive mechanisms.

PMID- 7817701
TI  - Secondary chronic myelogenous leukemia: a diverse pathogenesis?
AB  - A patient with myasthenia gravis and a thymoma did not respond to thymectomy. He
      was submitted to radiotherapy concurrent with steroid therapy followed by an
      alkylating based chemotherapy. Four years later, he developed an otherwise
      typical Philadelphia chromosome/BCR-ABL positive chronic myelogenous leukemia
      (CML) that quickly evolved to a blast crisis. We discuss the possible cause
      effect mechanism between the previous treatment and CML, and suggest that a
      distinct mechanism, albeit unknown, could be involved in the development and
      progression of secondary CML.

PMID- 7817700
TI  - [Determination of bile acids in stools of patients with colonic neoplasms and
      adenomatous polyps].
AB  - Since several years ago, the biliar acids have been incriminated in the
      etiopathogeny of colon cancer and adenomatous polyps, above all the secondary
      ones, involved by its aggressive action over the colonic epithelium in these
      mechanisms. The dietetical habits of developed countries have the high
      responsibility for this situation, their food pattern being a high animal fat
      diet, high in refined carbohydrates, animal proteins and low in dietetic fiber
      (diet type "occidental") unlike to developing countries that have a high natural
      fiber diet, having a much lower incidence in colon cancer and adenomatous polyps.
      Dietetic fiber has been studied considering it with a protector effect over the
      aggressive action of biliar acids on the colon mucous. We have studied 60
      patients, 20 of them with colon cancer, 20 with adenomatous and 20 case controls
      without colonic pathology. All of them had total high biliar acids in stools, a
      dietetical screening was carried out to determine the intake of animal fat and
      dietetic fibre during a week. There was a significant correlation in cases of
      cancer, polyps and biliar acids high in stools. There was also a significant
      correlation between the undue dietetic habits in colon cancer patients and high
      bilar acids. In those cases of adenomatous polyps, there was not a significant
      relation to dietetic habits.

PMID- 7817702
TI  - Interleukin-4 in chronic myelomonocytic leukemia. Growth suppression of
      hematopoietic precursors in the chronic phase and stimulation in the acute phase.
AB  - We examined the effects of interleukin-4 (IL-4) on the growth of hematopoietic
      precursors from a patient with chronic myelomonocytic leukemia (CMMoL). In the
      chronic phase of the disease, IL-4 inhibited spontaneous colony formation by
      CMMoL cells in semi-solid culture. However, in the acute phase, IL-4 promoted
      colony formation. These effects of IL-4 were abolished completely by the addition
      of anti-IL-4 neutralizing antibodies. The spontaneous colony formation by CMMoL
      cells in both the chronic and acute phases was inhibited by the addition of anti
      IL-6 antibodies. On the other hand, neither anti-IL-6, anti-granulocyte
      macrophage colony-stimulating factor (GM-CSF), anti-IL-1 beta nor anti-tumor
      necrosis factor alpha (TNF alpha) antibodies inhibited IL-4-induced colony
      formation by CMMoL cells in the acute phase. IL-4 suppressed the production of IL
      6 by CMMoL cells in both the chronic and acute phases. These results suggest that
      in the present patient, IL-4 suppressed the IL-6-mediated autocrine growth of
      CMMoL cells in both the chronic and acute phases, but directly stimulated their
      growth in the acute phase.

PMID- 7817703
TI  - Prophylaxis of symptoms of hyperhistaminemia after the treatment of acute
      promyelocytic leukemia with all-trans retinoic acid.
AB  - A 61-year-old man with acute promyelocytic leukemia (APL) is described in whom
      some leukemic promyelocytes contained granules similar to those of basophils, and
      hyperhistaminemia developed after treatment with all-trans retinoic acid. The
      symptoms of hyperhistaminemia, mediated via H2 receptors, were prevented by the
      administration of an H2-blocker, famotidine, but wheezing due to bronchospasms,
      mediated via H1 receptors, developed and was improved by administration of
      chlorpheniramine. In APL, it is generally thought that the maturation of
      neutrophilic leukocytes is arrested at the level of abnormal promyelocytes.
      However, heterogeneity of leukemic promyelocytes has been described and in a few
      patients some leukemic promyelocytes have been known to show basophilic features.
      Marked basophilia and severe symptoms due to hyperhistaminemia have recently been
      reported after the treatment of APL with all-trans retinoic acid. Our case
      presented similar basophilic features, but indicated that the symptoms of
      hyperhistaminemia after administration of retinoic acid can be prevented with
      antihistaminic drugs and suggested that both H1- and H2-blockers should be
      administered to such APL patients with basophilia.

PMID- 7817704
TI  - Red cells, HLA and platelet antibody formation in patients with multiple
      transfusions.
AB  - Totally 436 Chinese patients having received multiple transfusions of red cells
      and platelets on more than three occasions were screened for red cell antibodies.
      Twenty-six (6%) of them were positive. Anti-E, -Mia, and -c were the common
      alloantibodies. Nine patients were immunized during the period of regular
      transfusions, with a newly immunized rate of 2% (9/436). Among 436 patients, 387
      were screened for HLA antibodies by lymphocytotoxicity test (LCT). The overall
      positive rate was 35%. Most of the antibodies identified were against the high
      frequency HLA antigens in the Chinese population. About 10% of the LCT-positive
      cases reverted to negative state during the follow-up period. After chloroquine
      stripping of the target platelets, mixed passive hemagglutination assay was used
      to detect platelet antibodies other than HLA antibody. Fifty-eight of 161 cases
      (36%) were positive for platelet antibodies, but half of them disappeared within
      1 month. Nineteen of the 58 patients had sepsis and 2 had jaundice. These
      findings suggested that HLA and platelet antibodies are common among Chinese,
      though their clinical significance and the role in platelet damage are doubtful.

PMID- 7817705
TI  - Non-genetic leuko-neutropenia is related to dietary cholesterol: an experimental
      model with the rat.
AB  - A dietary factor is thought to be responsible for constant non-genetic
      neutropenia in Africans. The identify of this factor is unknown. The effect of
      diet on the differential white cell count in rat is studied. Twenty rats were
      divided into four dietary groups: (1) control rats on pellets, (2) millet, (3)
      peanut and (4) a special diet containing high cholesterol and saturated fatty
      acids from coconut, egg yolk, milk and Danish butter. After 3 months, group 4
      rats had significantly higher total white cell counts and percentages of
      neutrophils in addition to higher serum cholesterol levels and higher weights. In
      the second experiment, pure cholesterol was injected intraperitoneally to rats
      while control rats received saline. Neutrophil counts increased 6 h after
      injection and peaked only in the test rats. It is concluded that low-cholesterol
      diet decreases neutrophil count.

PMID- 7817706
TI  - Decreased phagolysosomal fusion of peripheral blood monocytes from patients with
      thalassemia major.
AB  - We evaluated the phagolysosomal fusion of peripheral blood monocytes from 15
      patients with thalassemia major and 10 thalassemia major carriers using a
      cytomorphological method with acridine orange as fusion marker. The monocyte
      phagolysosomal fusion of thalassemic patients was decreased (49.6 +/- 8.6%, mean
      +/- SD) and differed significantly (p < 0.05) from those of carriers and normal
      controls (65.7 +/- 11.4% and 74.6 +/- 5.7%, respectively). In vitro deferoxamine
      partially improved monocyte phagolysosomal fusion of patients with thalassemia
      major, and did not affect monocyte function in carriers and healthy subjects.
      Furthermore, in vitro addition of ferrous sulfate decreased normal phagolysosomal
      fusion. We conclude that the monocyte phagolysosomal fusion dysfunction of
      thalassemic patients could be related to iron overload.

PMID- 7817707
TI  - Production of immunoglobulin isotypes by peripheral blood mononuclear cells in
      multiple myeloma.
AB  - The immunoglobulin (Ig) isotype (IgG, IgA, IgM) production of peripheral blood
      mononuclear cells from 28 patients having multiple myeloma (MM) was analyzed. The
      total Ig secreting capacity of the cells, as measured by ELISA from the cell
      culture medium, was not found to be significantly reduced in MM (1,118 +/- 1,394
      micrograms/l) as compared to the values of 9 controls (898 +/- 520 micrograms/l),
      but a significant isotype switching towards the tumor paraprotein type was
      observed in the patients with active MM (p < 0.001). The percentage of IgG in the
      active IgG-MM was 88 +/- 11% and that of IgA in the active IgA-MM 83 +/- 13%, the
      control values being 44 +/- 11% for IgG and 44 +/- 13% for IgA. The proportions
      of isotypes resembled those of the controls in the inactive phase of the disease.
      Despite this dominating paraprotein class isotype production, no evidence of Ig
      gene clonal rearrangements was found in cells studied by either Southern blotting
      or the more sensitive polymerase chain reaction method, which suggests that
      polyclonal rather than monoclonal PB B cells are responsible for the Ig
      production observed.

PMID- 7817708
TI  - Molecular basis and haplotype analysis of delta, beta-thalassemic chromosomes in
      Greece.
AB  - The molecular defect was defined in 38 delta beta-thalassemic chromosomes from 30
      unrelated heterozygous and 4 homozygous patients of Greek origin. Restriction
      fragment beta-gene cluster haplotypes were studies in 23 delta beta-thalassemic
      chromosomes. The molecular lesion was identical in all studied cases and
      corresponds to the 'Sicilian' type of delta beta-thalassemia. Restriction
      haplotypes analysis has shown that, with one exception only, all Greek delta beta
      thalassemic chromosomes bear the polymorphic sites which characterize haplotypes
      I or VII, the former being probable by indirect evidence. The striking
      similarities of the molecular lesion and the underlying haplotypes are consistent
      with two theories: (1) The deletion occurred once on a chromosome and spread all
      over Greece and the Mediterranean area thereafter; (2) the 5' subhaplotype +---
      favors the deletional event in the delta-beta gene area.

PMID- 7817709
TI  - 8;21 and 15;17 translocations: abnormalities in a single cell lineage in acute
      myeloid leukemia.
AB  - We studied lineage involvement in two cases of acute myeloid leukemia (subtypes
      M2 and M3 expressing translocations 8;21 and variant 15;17, respectively) using
      the combined immunophenotype and chromosome painting technique known as the MAC
      (Morphology Antibody Chromosomes) method. We only found the translocations in
      CD13-positive granulocytic metaphases and not in glycophorin-A-positive erythroid
      metaphases. These results suggest that the translocations 8;21 and 15;17 only
      appear in one cell lineage. The karyotype of the cells with a variant 15;17
      translocation was 46;XX,der(1)t(1;15)(p?21;
      q?22)t(1;17)(q?23;q?12),der(15)t(1;15)(q?23;q?22),der(17)t(1;17)(p?21;
      q?12)/46,XX.

PMID- 7817710
TI  - Biochemical characterization of four new erythrocyte pyruvate kinase variants.
AB  - Pyruvate kinase (PK) from four patients with moderate to severe congenital non
      spherocytic haemolytic anaemia was characterized by methods recommended by the
      ICSH. The possibility that two of the patients are true homozygotes cannot be
      ruled out, while the other two apparently represent double heterozygotes. All but
      one had levels of PK activity between 44 and 65% of normal. The variant enzymes
      were designed 'PK Pontos', 'PK Macedonia', 'PK Athens' and 'PK Larisa'. Multiple
      physicochemical as well as kinetic aberrations were detected in the above
      variants. Their altered kinetic behaviour is discussed in terms of the concerted
      transition model for allosteric enzymes and their abnormal properties are
      compared with other known variants, while it is also attempted to correlate them
      with possible mechanisms resulting in chronic haemolytic anaemia.

PMID- 7817711
TI  - Hodgkin's disease associated with chronic myeloid leukemia. Determination of bcr
      abl rearrangement in paraffin-embedded tumors using the polymerase chain
      reaction.
AB  - A patient showing lymph node enlargement and tumors in the neck and axilla in the
      course of Philadelphia (Ph1) chromosome-positive chronic myeloid leukemia (CML)
      was seen. There were no hematological findings suggestive of crisis. RNA was
      isolated from formalin-fixed and paraffin-embedded tissue specimens for the
      polymerase chain reaction of bcr-abl. CML-type products were detected in the
      peripheral blood, but no bcr-abl products were found in the lymph nodes. These
      findings indicate a very rare case in which Hodgkin's disease developed during
      the course of CML.

PMID- 7817712
TI  - Developmental characteristics of trisomy 19 mice.
AB  - Trisomy 19 (Ts19), the only murine trisomy compatible with survival beyond birth,
      allows systematic studies on the effect of an additional chromosome upon
      postnatal development. In this review, developmental consequences of murine Ts19
      are presented. In Ts19 mice, viability is limited to a few weeks postpartum. Body
      weight is markedly reduced. The occurrence of malformations of the
      cardiovascular, skeletal and central nervous systems depends on the parental
      genetic background. In all organ systems examined, development is delayed by 1-2
      days. Ts19 hematopoietic cells exhibit the same survival rate in lethally
      irradiated hosts as controls. In the CNS, morphological and morphometric studies
      fail to detect cytoarchitectonic abnormalities: the orderly pattern of
      development is not disturbed in the visual cortex, cerebellum, locus coeruleus
      (LC), optic nerve and retina; but neurogenesis, gliogenesis, myelination and
      invasion of blood vessels are each delayed by 1-2 days. In addition, size and
      cell number of different brain regions are reduced to a variable degree: the
      telencephalon and the cerebellar vermis are markedly hypoplastic, whereas the LC,
      the optic nerve and the retina are hardly reduced in size. Choline
      acetyltransferase activity is selectively reduced in the Ts19 telencephalon,
      whereas the activity of the marker enzyme of the GABAergic system is decreased in
      all brain regions examined. In behavioral tests, visual capacities and
      orientation ability of Ts19 mice develop with a 2-day delay, while motor
      coordination is more severely retarded; there is no response to auditory
      stimulation. Fetal Ts19 ovaries show excessive oocyte degeneration. Development
      of the testes is only disturbed postnatally: differentiation of gonocytes to A
      spermatogonia and formation of B spermatogonia are severely disrupted, resulting
      in a striking reduction in germ cell number and a predominance of Sertoli cells.
      Histopathological changes exhibit marked intra- and interindividual variations.
      In addition, growth and lumen formation are impaired in the seminiferous tubules.
      The proliferative capacity of cultured Ts19 cells is not altered. The activities
      of glutamate oxaloacetate transaminase-1 and phosphoglycerate mutase-1 are
      increased by 50%, compatible with a gene dosage effect of these two enzymes.
      Ganglioside composition is altered in the Ts19 liver, but not in the brain,
      spleen and heart. Two-dimensional protein patterns show both chromosome-specific
      and chromosome-nonspecific changes, their frequency being far lower than expected
      from the number of proteins coded on chromosome 19. Possible pathogenetic
      mechanisms are discussed.

PMID- 7817713
TI  - Differential lectin binding to the fibrinoid of human full-term placenta:
      correlation with a fibrin antibody and the PAF-Halmi method.
AB  - Placental fibrinoid is thought to contain various glycoproteins originating from
      cell secretion and tissue degeneration, occasionally merged with fibrin.
      Information on the characteristics and derivation of the various fibrinoid
      components, however, is still fragmentary. Therefore, the present histochemical
      study on acetone-fixed placental tissue sections compared the staining pattern of
      FITC-conjugated lectins from Ulex europaeus (UEA-I), Bandeiraea simplicifolia (BS
      I) and Lycopersicon esculentum (LEA) with the reactivity of a fibrin antibody and
      a modified paraldehyde-fuchsin stain. Using different color reactions, the latter
      histological method identified two types of fibrinoid, which correlated well with
      fibrin-type and matrix-type fibrinoid. Immunohistochemically, fibrin was detected
      at the intervillous border of the basal plate, in some inner parts and in
      perivillous fibrinoid. UEA-I bound to endothelial cells and partially to fibrin
      type fibrinoid of villi and the basal plate, thus indicating a reaction with
      immured and disintegrated remnants of endothelial and blood cells. LEA stained
      fibrin-negative (i.e. matrix-type) fibrinoid homogeneously within the basal
      plate; the small reactive areas within the perivillous fibrinoid may belong to
      degenerating trophoblastic residues, because in villi LEA specifically reacted
      with the syncytiotrophoblast. BS-I heterogeneously labeled matrix-type fibrinoid
      deposits in the basal plate which surrounded decidual cells and subpopulations of
      extravillous trophoblast. In cell islands, BS-I also stained fibrinoid
      surrounding trophoblast cells heterogeneously. The data (1) confirm the existence
      of two types of placental fibrinoid, fibrin-type and matrix-type fibrinoid, (2)
      suggest that both types of fibrinoid contain different glycoconjugates, and (3)
      demonstrate the practical usefulness of the modified paraldehyde-fuchsin method
      for the identification of the two types of fibrinoid.

PMID- 7817714
TI  - Changes associated with the basal lamina during metamorphosis of Xenopus laevis.
AB  - We examined the changes in the morphology of the basal lamina of the colon,
      abdominal wall and tail muscles of tadpoles during metamorphosis and compared our
      results to those previously obtained for the small intestine. At the early stage
      of metamorphic climax (stages 60-62), we observed a curving of the basal lamina
      along the processes of the epithelial cells. At a later stage of metamorphic
      climax (stages 63-66), more extensive curving and folding of the basal lamina
      were observed. The basal lamina of the mesothelial cells in the abdominal wall
      did not change extensively as compared to the colon. Folded basal lamina was
      observed among degenerated muscle cells. Our results suggest that the folding of
      the basal lamina depends on the degree of deformation of the particular organ,
      which occurs mainly by physical factors such as the shortening or shrinking of
      the organ due to cellular degeneration. Cells that are newly differentiated
      produce an additional basal lamina, which results in transient doubling or
      layering. The combination of physical factors and cell differentiation results in
      a basal lamina that is more complex and contains folds and layers.

PMID- 7817715
TI  - The tunica media of the thoracic duct contains a heterogeneous population of
      muscle cells.
AB  - The three-dimensional cyto-architecture and ultrastructure of cells composing the
      different regions of the tunica media of canine and feline thoracic ducts (ThD)
      were investigated by scanning and transmission electron microscopy. The tunica
      media of the intervalvular regions consists of 2-4 layers of circulatory oriented
      ribbon-like smooth muscle cells (SMCs) of the contractile phenotype. Spot-like
      membrane contacts similar to gap junctions were observed between SMCs. In the
      parietal part of the valve's sinus (PPVS), modified SMCs containing large lipid
      droplets were found. Occasionally, in the upper thoracic part of the ThD in the
      PPVS, we observed cardiomyocyte-like cells (CMLCs) arranged as circularly
      oriented bundles. Frequent interdigitation contacts were formed between SMCs and
      CMLCs, suggesting a possible involvement of the latter cell type in pacemakers
      activity in the ThD.

PMID- 7817716
TI  - Development of the human gigantocellular reticular nucleus: a morphometric study.
AB  - The cytoarchitectonic development of the human gigantocellular reticular nucleus
      (GRN) was studied quantitatively in 15 fetuses (16-39 weeks of gestation: WG) and
      in 2 adults (16 and 85 years old). With microscopic observation on serial
      celloidin sections of the brain, we measured them to obtain the following
      morphometric parameters: numerical density (ND), profile area (PA), and perimeter
      (PL) of the GRN neurons. GRN appeared as early as early as 16-18 WG, but most
      neurons were still immature and the cell nucleus was relatively large
      (nucleocytoplasmic ratio was high), although a few large neurons containing fine
      Nissl bodies were observed. Typical, coarse Nissl bodies of large multipolar
      neurons were first recognized at 21 WG. The earliest myelination was noticed at
      22-23 WG, but myelinated nerve fibers were not prominent until the late fetal
      period. ND was largest at 16 WG and decreased rapidly with gestational age
      (coefficient of correlation, r = -0.85): it was reduced to about 10% of that at
      16 WG by the end of the fetal period. ND was smaller in the adults than in the
      fetuses. Average PA increased monotonously with gestational age (r = 0.79). The
      coefficient of variation (CV) of PA was high early in the fetal period (47-48%;
      16-18 WG) and increased gradually with age (r = 0.40). The average circulatory
      ratio (CR = 4 pi PA/PL2) decreased monotonously with gestational age (r = -0.85),
      while the CV of CR increased (r = 0.76). In conclusion, this study suggests that
      immature GRN neurons may appear by 16 WG after migration and that the subsequent
      differentiation and maturation may progress gradually and monotonously during the
      later half of gestation.

PMID- 7817717
TI  - Synaptic relations of GABAergic neurons in the area postrema.
AB  - gamma-Aminobutyric acid (GABA)-like immunoreactive neuronal profiles and their
      synaptic relations in the area postrema of the rat were studied by
      ultrastructural immunocytochemistry using an antibody directed against GABA. GABA
      like immunoreactive (GABA-LI) perikarya and dendrites usually received synaptic
      inputs from nonimmunoreactive axon terminals. These synaptic contact zones were
      mostly asymmetrical. Conversely, GABA-LI axon terminals were found to make
      synapses with nonimmunoreactive perikarya and dendrites, usually of the
      symmetrical type. Furthermore, GABA-LI axon terminals in synaptic contact with
      GABA-LI perikarya and dendrites were sometimes found. Although some GABA-LI axon
      terminals were in close vicinity of other nonimmunoreactive axon terminals, no
      clear synaptic contacts could be found. On the other hand, GABA-LI profiles could
      be found close to the capillaries, although they were always separated by a thin
      layer of glial processes. The above results suggest that the GABAergic neuron
      receives information from both the circulating blood and other neurons and then
      performs its depressor function through other neurons.

PMID- 7817718
TI  - The venous drainage of the apical segment of the right lower pulmonary lobe.
AB  - Fifty right lungs taken from dead human bodies of both sexes (30 male, 20
      female), whose ages ranged from 16 to 81 years, were studied. The left atrium,
      pulmonary veins and right main bronchus were injected with a 65% solution of
      Duracryl and then digested in sulphuric acid. The specimens were examined to
      determine the number and tributaries of the apical segmental veins of the lower
      lobe. Their length was 36 mm at the most and their diameter 8 mm. Four atypical
      kinds of tributaries from other segments were distinguished in every fourth case
      examined, and 5 kinds of accessory veins opening into the immediate veins were
      present, likewise in every fourth case examined.

PMID- 7817719
TI  - Morphogenesis of the osteo-architecture in the carnassial region of the feline
      mandible, as demonstrated by microfocal radiography.
AB  - For the first time, osteogenesis was observed using direct magnifying
      microradiography, a noninvasive technique that has a high power of resolution.
      Thus, it was possible to correlate different stages of bone maturation in the
      feline mandible with specific functional demands. Our observations suggest a
      relationship between osseous structure and the mode of feeding and content of the
      diet.

PMID- 7817720
TI  - The sesamoid bone of musculus abductor pollicis longus (os radiale externum or
      prepollex) in primates.
AB  - The sesamoid bone of the musculus abductor pollicis longus has been investigated
      in a series of 276 nonhuman primates representative of 37 genera, and in a series
      of 300 radiographs of human subjects. The presence of this ossicle in primates is
      a primitive characteristic. It is present in all nonhuman primates, and is
      generally articulated with both the scaphoid and trapezium. Modifications of the
      general mammalian pattern exist only in Gorilla gorilla, where the sesamoid bone
      is observed in about half of the individuals, and in Homo, where this ossicle is
      normally absent.

PMID- 7817721
TI  - Superficial branch of the radial nerve emerging between two slips of a split
      brachioradialis muscle tendon: a variation of possible clinical relevance.
AB  - One hundred and fifty upper extremities of 75 nonrandomized human cadavers were
      dissected to study the topographical relationship between the brachioradialis
      muscle tendon (BRMT) and the superficial branch of the radial nerve (SBRN). A
      split BRMT was found in nine arms, while in five of those nine arms the SBRN
      emerged from under the brachioradialis muscle between the two slips of a divided
      BRMT to become superficial. This topographical relationship is mentioned sparsely
      in very old literature, yet its frequency has not been studied before. Further
      clinical investigations should be undertaken to study the clinical relevance of
      the above-mentioned topographical relationship.

PMID- 7817722
TI  - Methotrexate treatment of ectopic pregnancy.
AB  - The last decade has witnessed an increasing number of reports indicating that
      ectopic pregnancy (EP) can be successfully and safely treated with methotrexate
      (MTX). This review summarizes the results. In large series, as many as 45% of a
      population of women with EP has been treated with MTX. Success rates of 82-95%
      have been achieved. Tubal patency on the affected side was preserved in 79-91% of
      the cases. Preliminary assessment of subsequent fertility suggests that 47-69%
      will obtain an intrauterine pregnancy. Complications have been only few and of
      minor importance. However, the majority of reports do not include controls.
      Randomized studies are needed to optimize patient selection, treatment regimens,
      long-term toxicity, future fertility, and cost-benefits.

PMID- 7817724
TI  - Urinary trypsin inhibitor may have a protective effect on endothelial cells in
      preeclampsia.
AB  - Urinary trypsin inhibitor is a glycoprotein which has an inhibitory effect on
      many enzymes, especially neutrophil elastase. The concentration of urinary
      trypsin inhibitor in serum (maternal and fetal), urine and amniotic fluid was
      measured in 20 cases of preeclampsia and compared with levels in normal
      pregnancy. Urinary trypsin inhibitor levels were significantly increased in the
      maternal and fetal serum of preeclamptic patients compared to normal pregnancy (p
      < 0.0001), as well as in urine and amniotic fluid of the same patients. Relative
      fluorescence release of a calcium chelating agent (fura-2) from human umbilical
      vein endothelial cell cultures was significantly increased by preeclamptic serum
      compared to serum of normal pregnant women (p < 0.03). After incubation of
      urinary trypsin inhibitor with the cultures, significant decrease of fura-2
      release was observed (p < 0.03). Urinary trypsin inhibitor has an effect on
      suppression of activated neutrophils, elastase production and may have a
      protective effect on endothelial cells.

PMID- 7817723
TI  - Methotrexate in management of advanced ectopic pregnancy complicated by ovarian
      hyperstimulation syndrome.
AB  - A case of advanced ectopic pregnancy after in vitro fertilization complicated by
      an ovarian hyperstimulation syndrome is presented. Methotrexate was given in
      spite of high levels of hCG and appeared to be successful. Difficulties in the
      choice between surgical and conservative treatment are discussed.

PMID- 7817725
TI  - Conservative ambulatory management of prelabor rupture of the membranes at term
      in nulliparous women.
AB  - OBJECTIVE: To assess maternal and fetal outcome at conservative ambulatory care
      of nulliparous women at term with prelabor rupture of the membranes. METHODS: A
      prospective study of 176 women managed conservatively in an ambulatory setting
      (nonstress test and assessment of amniotic fluid index every second day).
      RESULTS: The median rupture of the membrane to delivery interval was 30 hours.
      Ninety per cent were delivered within 85 hours. The patients were divided into
      three groups according to the time period between rupture of membranes and
      delivery (under the 25th, 25th-75th and above the 75th centile). The maternal
      infectious morbidity (0, 6, 7% respectively), fetal distress (5, 18, 17%
      respectively) and instrumental delivery rate (5, 16, 16% respectively) tended to
      be increased in the upper three quartiles, without reaching a statistically
      significant level as analysed by chi 2-test. Nonstress test or evaluation of
      amniotic fluid index was not able to predict intrapartum fetal distress. In no
      case was there a delay in the management of any complication due to the
      ambulatory care. CONCLUSION: Awaiting spontaneous labor in nulliparous women with
      prelabor rupture of the membranes at term does not seem to be associated with any
      obvious advantage. If, however, a conservative attitude is implemented, the
      patients can preferably be treated on an ambulatory basis.

PMID- 7817726
TI  - Increased concentration of the free beta-subunit of human chorionic gonadotropin
      in hyperemesis gravidarum.
AB  - OBJECTIVE: The amount of free beta subunit hCG (free beta) has been reported to
      be increased in trophoblast disease and Down's syndrome, conditions also
      associated with high total hCG. Increased total hCG has been reported in
      hyperemesis gravidarum. We sought to determine if sera from singleton gestations
      with hyperemesis gravidarum contained a higher proportion of free beta hCG
      compared to controls of comparable gestational age. METHODS: Sera from 39
      patients with hyperemesis gravidarum was compared with that from 23 control
      subjects of comparable gestational age with respect to beta hCG and its subunits
      (free beta and free alpha). RESULTS: Hyperemesis patients and controls were
      comparable with respect to age, weight and gestational age. The concentration of
      hCG was greater in hyperemesis patients (9237 +/- 3613 ng/ml, mean +/- s.d.)
      compared to controls (5543 +/- 2290, p < 0.005) as was the concentration of free
      beta hCG (101 +/- 70 ng/ml vs. 31 + 31, p < 0.001). Free alpha did not differ
      between hyperemesis patients and controls (399 +/- 231 ng/ml vs. 377 +/- 214). A
      percent free beta greater than 0.6 was found in 33/39 hyperemesis patients (85%)
      compared to 5/23 controls (22%), p < 0.001. CONCLUSION: Increased free beta hCG
      is found in hyperemesis gravidarum. This finding strengthens the association of
      hyperemesis with abnormal metabolism of hCG.

PMID- 7817727
TI  - Maternal health care program and markers for late fetal death.
AB  - OBJECTIVE: To identify markers for late fetal death, a multicenter study was
      performed, based on routinely obtained data from maternal health care units.
      MATERIAL AND METHODS: Prospectively recorded data were obtained from maternal
      health care units belonging to five delivery units. In all, 233 consecutive cases
      of singleton pregnancy involving late fetal death (> or = 28 weeks) were
      identified between 1983 and 1989. As a control for each case, the next
      consecutive mother giving birth to a live infant at the same delivery unit was
      selected, the sole matching criterium being parity. RESULTS: After exclusion of
      pregnancies with lethal malformations or trauma, 205 cases remained for the
      statistical analysis. Two main subgroups were identified: mothers with placental
      abruption (n = 44), and pregnancies with no obvious reason for fetal death (n =
      101). An increased risk for late fetal death was evident in expectant mothers >
      or = 40 years (10 vs 1; chi 2 = 7.6, p < 0.01), and in smokers where an
      association was seen to placental abruption. A significantly increased risk was
      also seen in women with medical treatment for essential hypertension (8 vs 1; chi
      2 = 5.6, p < 0.05). On the other hand, we found no correlation between
      proteinuria, glucosuria, decreasing symphysis-fundal height, or changes in the
      Hb, on the one hand, and late fetal demise, on the other. There was no
      overrepresentation of post dated pregnancy (by ultrasound early in the second
      trimester) among the cases. Nor did post dated pregnancies (> or = 42 weeks)
      estimated from first day of last menstrual period (but not post dated by
      ultrasound) imply a higher rate of fetal death, as has been suggested in previous
      studies. CONCLUSION: In the present material, there was no sign of systematic
      error in the evaluation of data routinely obtained from the antenatal clinics and
      maternity units. Apart from placental abruption in smokers, a high maternal age,
      and medical treatment for essential hypertension, deviating data were recorded as
      often among controls as among cases. No correlation was evident between a post
      date pregnancy and fetal demise. A short symphysis-fundal height was recorded as
      often among controls as among cases and the even distribution of fetal
      birthweight in case pregnancies around the standard curve for the normal
      population is noteworthy.

PMID- 7817728
TI  - No relation between maternal weight gain and stillbirth.
AB  - BACKGROUND: To evaluate the relationship between stillbirth in singleton
      pregnancy (> or = 28 weeks gestation) and maternal weight (weight gain) from 24
      completed weeks. METHODS: All fetal deaths (n = 210) at five delivery units
      during seven years in southern Sweden were analysed. To each case a control
      mother was selected, the only matching criteria being parity and place of
      delivery. Regression analysis was used for comparison of body weight gain in
      cases and controls. RESULTS: Mothers experiencing stillbirth had a significantly
      lower mean body weight at 24 weeks gestation than control mothers (63.5 kg vs
      67.3 kg; t = 2.4, p < 0.05). No significant difference between cases and controls
      was found in mean weight gain during pregnancy from 24 completed gestational
      weeks to delivery, even when the last three measurements before delivery for
      cases and controls were compared separately. CONCLUSION: There is no difference
      in body weight gain between mothers with stillbirth and mothers giving birth to a
      live infant.

PMID- 7817729
TI  - Emergency cesarean section: the effect of delay on umbilical arterial gas balance
      and Apgar scores.
AB  - BACKGROUND: We wanted to conduct a prospective study on the dynamics of emergency
      cesarean section (ECS) in terms of fetal survival and morbidity. METHODS: The
      study covered 101 cases of ECS in Helsinki City Hospital, in which the time of
      alarm, the starting time of the operation, the time of birth, the umbilical
      arterial gas values, and Apgar scores were known. This group consisted of 60
      cases with the operating team in the hospital (group 1) and 41 cases with the
      team on call (group 2). Means of the parametric variables were compared by the
      analysis of variance using separate or pooled t-tests after Levene's test of
      variances. Difference between the rate of adverse outcome (dead or handicapped)
      in each group was calculated using chi-square test. RESULTS: In group 1, the time
      between the clinical decision and the time of delivery (mean +/- s.e.mean) was
      13.5 +/- 0.7 min, in group 2, 23.6 +/- 0.9 min. The groups did not differ in
      terms of birthweight, placental weight, Apgar scores, and umbilical arterial gas
      values, except for pO2. The mean pO2 in group 1 was lower (1.9 +/- 0.1 kPa) than
      in group 2 (2.5 +/- 0.2 kPa). p = 0.0023. In group 2, one infant was handicapped
      by hypoxic ischemic encephalopathy and three fetuses had died in utero. The rate
      of survivors was significantly higher when the operating team was in hospital (p
      = 0.05). CONCLUSION: The risk of fetal loss is evident when the operating team is
      on call outside the hospital, at least if the alarm to operation interval exceeds
      20 minutes. The present study suggests that 24-hour services of anesthesia and
      operating theater personnel are crucial for optimal management of emergent
      situations in the delivery room.

PMID- 7817730
TI  - A study of the effect of rotational forceps delivery on fetal acid-base balance.
AB  - OBJECTIVE: To determine whether Kiellands forceps rotational delivery causes a
      significant reduction in fetal pH or base excess, as compared to a control group
      delivered using non-rotational forceps. DESIGN: A prospective observational
      study. SETTING: A teaching hospital labor ward in the UK. METHODS: Fetal blood
      sampling was performed prior to delivery by Kiellands forceps (n = 26) or by non
      rotational forceps (n = 24). Following delivery, the umbilical vein was sampled.
      OUTCOME MEASURES: The changes in fetal pH and base excess. RESULTS: No
      significant changes in pH were noted in fetuses delivered using Kiellands forceps
      or in those delivered using Neville Barnes forceps. However, whilst no changes in
      base-excess were found in the fetuses delivered using Neville Barnes forceps,
      there were significant changes in base-excess in those fetuses delivered using
      Kiellands forceps. CONCLUSION: This small study suggests that delivery by
      Kiellands forceps may result in a significant deterioration in fetal acid-base
      balance.

PMID- 7817732
TI  - A new technique to test tubal patency under transvaginal sonographic control.
AB  - OBJECTIVE: Since 1990 we have undertaken a trial to evaluate if TVS, even without
      contrast media, could diagnose tubal patency. MATERIALS AND METHODS: A detailed
      description of the technique is given. Two hundred and seventy-three patients
      underwent sonosalpingography in our department in the period 1990-1993. The
      sonographic findings were matched in 43 cases to hysterosalpingography and in 55
      cases to laparoscopy. RESULTS: Tubal patency was demonstrated in 218 patients
      (80.5%), monolateral patency in 41 (15.1%) patients and bilateral tubal occlusion
      in 12 (4.4%) patients. In the 43 patients undergoing hysterosalpingography,
      discordance between the two examinations was observed in five cases (11.6%).
      However, only six out of 86 salpinxes had different results (6.9%). In only one
      case was total discordance observed. In three out of four other cases the
      difference was due to patency diagnosed at SSG and occlusion at HSG. Of the 55
      patients undergoing laparoscopy 12 cases (21.8%) had discordant results. Complete
      discordance was observed in two cases while in ten cases one salpinx had a
      different patency report. The discordance goes to 12.7% when we take into account
      all the salpinxes evaluated. CONCLUSION: Sonosalpingography gives very similar
      results to hysterosalpingography and may be used on clinical basis for tubal
      patency evaluation.

PMID- 7817731
TI  - Ultrasonographical and hormonal description of the normal ovulatory menstrual
      cycle.
AB  - OBJECTIVE: To describe the changes in uterine volume, endometrial thickness and
      follicular size during the normal menstrual cycle by use of transvaginal
      ultrasonography and to correlate these changes with the endocrine events in the
      same cycle. METHODS: A group of 23 healthy women with normal body mass index and
      with a history of regular menstruations were monitored with repeated hormonal and
      vaginal ultrasonographical investigations during the menstrual cycle. RESULTS:
      Sixteen of the women fulfilled the hormonal criteria for ovulation. The mean
      length of the cycles was 28 days (range 25-30 days) with a mean length of the
      follicular and the luteal phases of 14.4 days (range 12-17 days) and 13.5 days
      (range 12-16 days), respectively. The estradiol level in serum the day before the
      peak of the luteinizing hormone varied between 490 and 1710 pmol/l (mean 1087
      pmol/l). Ultrasonographically, the most clinically relevant changes were the
      increase in diameter of the dominant follicle and the growth of the endometrium.
      At ovulation the dominant follicle had a mean diameter of 21.4 mm (range 17.4
      27.0), whereas the endometrium had a mean thickness of 12.8 mm (range 10.0-15.9).
      When analysed over the entire follicular phase, the serum estradiol concentration
      correlated both with the diameter of the dominant follicle (r = 0.93, p = 0.0001)
      and with the thickness of the endometrium (r = 0.79, p = 0.0001). However, no
      such correlations were found when only the last part of the follicular phase was
      analysed. In the luteal phase there was no correlation between the size of the
      corpus luteum and the serum concentration of progesterone. CONCLUSIONS: Vaginal
      ultrasonography is a practical and reliable method to monitor structural changes
      in the ovaries and the uterus during the menstrual cycle. The results are of
      clinical importance for a better understanding of the physiological changes and
      helpful when monitoring induction of ovulation in assisted reproduction.

PMID- 7817733
TI  - Vaginal discharge--comparison of clinical, laboratory and microbiological
      findings.
AB  - Of 101 fertile women (15-50 years of age) consulting in general practice due to
      vaginal discharge and/or genital malodor, bacterial vaginosis was diagnosed in
      34% and vaginal candidiasis in 23%. The presence of Chlamydia trachomatis,
      Trichomonas vaginalis, genital herpes virus and Neisseria gonorrhoeae was
      demonstrated in 15%, 9%, 7%, and 1% of cases, respectively. No specific genital
      tract pathogens were found in 25 patients, where the clinical diagnosis was
      psychological factors (n = 5), intra-uterine device-associated discharge (n = 5),
      cytolytic vaginosis (n = 5), urinary tract infection (n = 3), or other/unknown
      causes (n = 7). In most cases diagnosis of bacterial vaginosis, vaginal
      candidiasis or trichomoniasis was established by clinical examination and simple
      office tests (pH indicator paper, amine test, microscopy of wet smear, yeast
      culture kit). C. trachomatis and N. gonorrhoeae were diagnosed by means of
      culture, cervicitis being diagnosed clinically in five of 15 cases with culture
      confirmed chlamydial infection, while gonorrhoea was suspected from findings in a
      stained cervical smear. Sexually transmitted micro-organisms were detected in 16%
      of women with bacterial vaginosis or candidiasis. Of 29 women with sexually
      transmitted agents, 14% harbored more than one such organism.

PMID- 7817734
TI  - Onset and duration of hypoalgesia following application of lidocaine spray on
      genital mucosa.
AB  - Lidocaine spray is used as a topical analgesic prior to minor surgical procedures
      performed on genital mucosa. In this study onset and duration of hypoalgesia on
      the genital mucosa was investigated by spraying lidocaine solution on the mucous
      membranes of female genitals with subsequent measurements of pin prick pain
      thresholds induced by argon laser stimulation. A dosage of 50 mg of lidocaine
      spray was administered to the genital mucosa of the inside of the labiae minora.
      Repeated measurements of pain threshold were performed until normal sensitivity
      was reached. Analgesia to 1.5 W laser stimulation was obtained in all volunteers
      after an average of 2.7 min +/- 1.3 min (s.d.) (Range: 1-4 min). The effect
      lasted 29.7 min +/- 8.9 min (s.d.) (Range 12-45 min). The application of
      lidocaine spray produced a painful, smarting sensation which, however,
      disappeared again after 15-30 seconds. The study suggests that minor surgery
      should not be performed earlier than 4 min after application of lidocaine spray
      and it is recommended that it should be remembered that the duration of analgesia
      varies between individuals and thus may be very short in some patients.

PMID- 7817735
TI  - Psychological responses following medical abortion (using mifepristone and
      gemeprost) and surgical vacuum aspiration. A patient-centered, partially
      randomised prospective study.
AB  - BACKGROUND: A substantial body of objective data now exists to support the
      consensus view that induced abortion results in a low incidence of psychiatric
      morbidity. However, these data do not include more recent advances in abortion
      technology. Medical abortion entails a participatory role on the part of the
      woman, who may perceive more pain or see products of conception. The physical and
      psychological events experienced by women undergoing this procedure may lead to
      differences in psychopathology. METHODS: 363 women undergoing legal induced
      abortion up to 63 days gestation were allocated by a prospective partially
      randomised design to undergo medical abortion (using mifepristone 600 mg followed
      48 h later by gemeprost 1 mg vaginal pessary) or vacuum aspiration performed
      under general anesthesia. This study design allowed women with a preference for a
      particular method to undergo that method; women without preferences were
      allocated at random. Women completed sensitive and reliable psychometric
      instruments (the Hospital Anxiety and Depression Scale and a semantic
      differential rating scale designed to measure self-esteem) prior to abortion and
      16 days later. RESULTS: There were no significant differences between women
      allocated at random to medical abortion or vacuum aspiration in post-abortal
      anxiety, depression or low self-esteem. Women with high levels of mood
      disturbance prior to abortion, who were smokers or who had medical complications
      following abortion were at highest risk of post-abortal mood disorder.
      CONCLUSIONS: Medical abortion is a psychologically safe as surgical vacuum
      aspiration. The quantitative findings of the study support the consensus view
      that abortion is associated with high incidence of psychological benefit,
      whichever method is used.

PMID- 7817736
TI  - The diagnostic value of transvaginal sonography in the diagnosis of endometrial
      malignancy in women with peri- and postmenopausal bleeding.
AB  - The purpose of this study was to evaluate transvaginal sonography and curettage
      in the diagnosis of endometrial malignancy in women with peri-, and
      postmenopausal bleeding. Diagnostic curettage has been the method of choice to
      diagnose endometrial cancer. The purpose of this study was also to evaluate the
      value of transvaginal sonography in decreasing the number of curettages, because
      the costs of curettage are huge today and only 10% of the women in this group
      will be diagnosed with endometrial cancer. Transvaginal sonography was performed
      on 353 women with peri- or postmenopausal bleeding before curettage. Endometrial
      malignancy was found in 42 patients, in 12/242 (5%) of women aged less than 60
      years and 30/111 (27%) of women aged 60 years or more. All the patients with
      endometrial cancer had an endometrial thickness of 6 mm or more measured by
      transvaginal sonography. The sensitivity of ultrasound to detect malignancy was
      100%, the specificity was 43.4%, the positive and negative predictive values were
      19.2% and 100%. If the limit of 6 mm of endometrial thickness had been used in
      this study, 38.2% of the curettages could have been avoided.

PMID- 7817738
TI  - Laparoscopic removal of ovarian cysts using a zipper storage bag.
AB  - Laparoscopic surgery has become increasingly popular in the management of pelvic
      masses. A major problem during laparoscopic surgery is removal of the specimen.
      The advantages of the bag retrieval technique using commercially available
      retrieval bag has been described. However, the size of the bags available is
      limited and they are relatively expensive. We describe the use of a zipper
      storage bag for the removal of ovarian cysts in 11 patients undergoing operative
      laparoscopy without spillage of the cyst contents, the need for abdominal wound
      extension or to perform a culdotomy. The operating time is reduced, compared to
      'purpose designed' bag retrieval systems. This technique is safe, easy to perform
      and cost-effective.

PMID- 7817737
TI  - Use of pap-smears in a population without a mass screening program.
AB  - STUDY OBJECTIVE: To analyze the use of Pap-smears in a population where a
      screening program was not offered. DESIGN: Retrospective analysis of pathology
      registry data on women resident in two counties of Norway. SETTING: Evaluation of
      opportunistic screening by age and year of birth. Proportion of population tested
      during successive 3-year periods. MATERIAL: 353,665 smears from 88,048 women
      examined since 1973. For this purpose we concentrated on 257,951 smears from
      77,431 women examined during the period 1981-90. RESULTS: Between 62 and 67% of
      women examined during each 3-year period were 20-39 years old, 14-16% were 50-69
      years of age. Throughout the ten-year period the frequency of Pap-smear testing
      of women over 60 and under 20 increased slightly whereas it decreased for women
      20-39 years old. Follow-up of positive or atypical smears comprised about 25% of
      all smears. The highest proportion of follow-ups was found among women 30-49
      years old. About one third of women aged 20-59 years had more than one smear
      taken in a 3-year period, follow-up smears excluded. CONCLUSION: More than half
      of the women aged 50 and above have no smears or smears less than one every third
      year. This proportion increases with age. The use and distribution of smears by
      age is still far from the situation expected in an organized screening program
      although a slight amelioration was observed through the study period.

PMID- 7817739
TI  - The cosmetic outcome of the scar formation after cesarean section: percutaneous
      or intracutaneous suture?
AB  - Three methods of skin closure after cesarean section were tested and compared in
      a prospective trial. Eighty-nine (82.5%) appeared for follow-up investigation 4-5
      months after delivery. The mean scar width was significantly narrower after
      phannenstiel incision compared with percutaneous nylon sutures after lower
      midline incision, 3.1 mm versus 11.3 mm. Intracutaneous continuous PDS-suture
      after lower midline incision produced scars 40% narrower than with percutaneous
      sutures, 6.8 versus 11.3 mm. 37.5% of the women sutured intracutaneously
      complained over persistent secretion after discharge from the hospital. Some of
      these complaints were probably due to the introduction of new materials and skin
      closure technique. None consulted a physician with their complaints, i.e. the
      complications were sub-clinical. Exclusion of the women with persistent
      secretions from the material led to significantly narrower scars compared with
      percutaneous closure, 4.5 versus 11.1. Thus, even better results can be expected
      as experience with the technique increases. Observer and patient satisfaction
      with the cosmetic outcome were measured independently on a 'Lasa-line'. Their
      opinions coincided; the order of acceptability was worst with percutaneous wound
      closure after lower midline incision, next best with intracutaneous closure after
      lower midline incision, and best after phannenstiel incision with intracutaneous
      closure.

PMID- 7817740
TI  - Pregnancy after cardiac surgery in patients with secondary pulmonary hypertension
      due to a ventricular septal defect.
AB  - Pulmonary hypertension is defined as pulmonary artery pressure greater than 30/15
      mmHg. The etiologies of pulmonary hypertension can be divided into primary and
      secondary ones. The causes of the latter include long-lasting left-to-right
      shunts (congenital cardiac defects e.g. ventricular septal defect), pulmonary
      thromboembolism and severe pulmonary disease (1). Women with pulmonary
      hypertension often tolerate the physiological changes of pregnancy poorly. We
      describe the intrapartum management and outcome of two patients who had undergone
      successful surgical closure of a ventricular septal defect several years earlier.
      They both had developed pulmonary arterial hypertension preoperatively but had an
      uneventful recovery and were clinically asymptomatic before pregnancy.

PMID- 7817741
TI  - Delayed maternal death after perimortem cesarean section.
AB  - We report a case of perimortem cesarean section performed on a multigravida with
      congestive heart failure. This patient had a past history of repeated episodes of
      acute myocarditis and this time, congestive heart failure attacked her at the
      36th week of gestation. The maternal condition deteriorated rapidly with frequent
      attacks of ventricular fibrillation and cardiac arrest, which gradually became
      unresponsive to active cardio-pulmonary resuscitation (CPR). The fetal condition
      also worsened accordingly. Cesarean section was therefore performed and a 2590 gm
      depressed female baby was delivered in less than one minute after skin incision
      and about twenty-seven minutes after the maternal condition became extremely
      unstable. The Apgar scores were 1 at one min, 4 at five min and 6 at ten min. The
      mother improved soon after delivery of the fetus and her consciousness returned.
      However, her condition deteriorated again and she died four hours after
      operation. The fetus survived and follow-up 21 months after delivery was normal.

PMID- 7817742
TI  - [Basal cell and basosquamous carcinomas of the external ear. Immunohistochemical
      study].
AB  - Malignant neoplasms of the external ear are difficult diseases of the cervical
      facial area to study clinically and therapeutically. The most frequent malignant
      histological patterns are spinocellular and basocellular carcinomas. Melanomas,
      basosquamous or "metatypical" carcinomas are less frequent. The latter have a
      transition histological pattern halfway between a basocellular and spinocellular
      carcinoma. In our experience, some external ear neoplasms, diagnosed as
      basocellular, were clinically more invasive (aggressive). Therefore we studied
      the immunohistochemistry of operative specimens with monoclonal antibodies (MoAb)
      with the purpose of revaluating the diagnosis after follow-up, and of detecting
      unrecognized basosquamous carcinomas. We studied 4 patients (2 male and 2 female)
      aged between 58 and 78, examined in the period 1990-92 an a diagnosed as having
      an external ear basocellular carcinoma. The immunohistochemical study was carried
      out using anti-CEA (carcinoembryonal antigen) monoclonal antibodies, high
      molecular weight acid anticytokeratins (anti-AE3) and low molecular weight basic
      anticytokeratins (anti-AE1). Appendage origin of the neoplasms was excluded after
      carrying out MoAb anti-CEA tests, negative in all patients. Epithelial origin of
      the neoplasms were confirmed after carrying out MoAb anti-AE3 tests, positive in
      all patients. After carrying out MoAb anti-AE1 tests, positive in 3 patients out
      of 4, we reviewed the classification of 2 basocellular carcinomas out of 4. These
      tumors evidenced an atypical dyskeratosis and a positivity for intracellular
      keratinization. These aspects were not evidenced in the previous histological
      examinations using routine stains and could be an index of unfavourable clinical
      evolution of these two cases from a basocellular carcinoma toward a more
      aggressive basosquamous carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7817743
TI  - [Carbon dioxide laser posterior ventriculocordectomy for treatment of bilateral
      vocal cord abductor paralysis].
AB  - Several surgical procedures have been proposed for the treatment of bilateral
      vocal cord abductor paralysis. All, whether conventional or microsurgical, are
      designed to achieve a compromise between phonation and respiration that ensures,
      however, good voice quality. In this study we present and discuss our preliminary
      results with C02 laser posterior ventriculocordectomy (PVC). This microsurgical
      procedure stems from the work of Chevalier-Jackson and extends the range of
      application of modern posterior cordectomy. Chevalier-Jackson's original idea
      (ventriculocordectomy) has been developed and integrated in the light of the most
      recent data on C02 laser posterior cordectomy. At our Institute, we have employed
      this technique in treating 13 patients with bilateral vocal cord abductor
      paralysis. The age range of these patients, 9 females and 4 males, was 33-80
      years. The etiology varied: iatrogenic post-thyroidectomy in 8 cases, post
      traumatic in 2, secondary to a central lesion in 3. In 3 patients a tracheostomy
      tube was in place upon hospitalization. Deglutition, even for fluids, was usually
      promptly recovered. Resting and external dyspnea improved in all those patients
      who had not been previously tracheotomized. It was possible to remove the
      tracheotomy the in two out of three cases. We found no evidence of iatrogenic
      glottic stenosis among our cases. In our experience, endoscopic laser posterior
      ventriculo-cordectomy has many advantages: the maneuvers are rapid, simple,
      straightforward and easy to perform; the operation is reliable and ensures
      adequate airway patency and freedom from dyspnea during daily activity. The risk
      of complications, such as granuloma or cicatricial stenosis, is low as as long as
      appropriate steps are taken before and during the operation.

PMID- 7817744
TI  - [The status of receptors in laryngeal carcinoma: a study of receptors for
      estrogen, progesterone, androgens and glucocorticoids].
AB  - In order to verify the hypothesized hormone sensibility of the laryngeal
      carcinoma, we evaluated the level of steroid receptors in this type of neoplasm
      and correlated this datum with common pathological and clinical prognostic
      indices. Estrogen and progesterone receptors were evaluated in 105 patients with
      a squamous cell carcinoma and 2 patients with a mucoepidermoid laryngeal
      carcinoma. Receptors for androgens and glucocorticoids were evaluated in 35
      patients (all with a squamous cell carcinoma). Dosage was performed on fresh
      neoplastic tissue using the DCC (Dextran Coated Charcoal) method. Estrogen
      receptors were present in 26 cases (24.3%); progesterone receptors were present
      in 18 cases (16.8%); both receptors were revealed in 8 patients (7.5%). Androgen
      receptors were evident in 4 patients (4/35, 11.4%); glucocorticoid receptors were
      evident in 7 patients (7/35, 20%); both receptors were revealed in 4 (11.4%)
      cases. No statistical difference with regard to grading, site and extension of
      the cancer, extralaryngeal tissue involvement or node metastasis was noted in the
      groups of patients with or without steroid receptors.

PMID- 7817745
TI  - [Combined craniofacial surgery in malignant tumors of the ethmoid].
AB  - The Authors discuss the importance of surgical treatment in ethmoid cancer basing
      their discussion upon observation of three cases involving the anterior skull
      base which followed an overview of the epidemiology, histology and evaluation of
      this kind of pathology. After reviewing Literature they stress the validity of
      anterior craniofacial resection which allows a wide exposure of the complex
      anatomic structures at the base of the skull and a monoblock resection of
      malignant tumors as well as a satisfactory reconstruction of the resulting defect
      at the skull base. Furthermore, they emphasize the still existing differences
      among many Authors as far as surgical technique is concerned and the extreme
      variability of the survival rate. The Authors conclude that in order to make a
      comparison between the results of different Authors, data concerning the site of
      origin, the extension and the histology of the tumors and the length of the
      follow-up should be more homogeneous.

PMID- 7817746
TI  - [Total/near-total glossectomy for advanced carcinoma of the tongue].
AB  - Poor survival rates and the limited palliation afforded by radiotherapy alone,
      together with progress made in reconstructive surgery in restoring mucosal
      continuity after large resections, make total glossectomy reasonably indicated
      for treatment of advanced carcinoma of the tongue. The Authors reviewed 19 cases
      (17 males, 2 females, mean age 58.4 years) of total and near total glossectomy
      without laryngectomy treated at National Cancer Institute "Regina Elena" of Rome
      from 1990 to 1993 in order to evaluate oncological and functional results. All
      patients were reconstructed immediately, 16 with a pectoralis major flap, 2 with
      a nasolabial flap and 1 with a radial forearm free flap and were available for
      follow-up from 6 to 45 months (mean 29 months). There was no operative mortality
      and no patient needed total laryngectomy for aspiration. The rate of local
      recurrencies was 52.6%, most of them (75%) in patients who had undergone
      total/near total glossectomy for recurrence. Survival rate was 61.5% after 1 year
      and 20% after 2 years. 94% of patients resumed swallowing and independent oral
      alimentation (48% of them without any dysphagia); 84%; of the patients were
      decannulated and 48% produced easily intellegible speech. Data from our
      experience let us conclude that, in the light of the acceptable functional
      results obtained with reconstructive flaps, total glossectomy should be
      considered as the primary treatment modality in advanced carcinoma of the tongue
      (including T2 > 3 cm exceeding midline), and should not be reserved only for
      salvaging hopeless situations.

PMID- 7817747
TI  - [Surgical protection: anatomic and diagnostic contribution of a new CT techniques
      in preoperative study of the temporal bone].
AB  - In the last ten years, CT study of the temporal bone has become, finer and has
      enriched itself with new projections. The objective of this paper fruit of
      collaboration between radiologist and otologist, is the search for CT
      projections, which evidentiate, with the same order and progression, the most
      important reference points that otologists find in temporal bone surgery. The
      study was conducted on fresh temporal bone extracted from cadavers which
      underwent tomography according to a projection very similar to a surgical plane
      defined precisely as "surgical". The Authors comment on what they consider the
      three most significant tomographies: those taken from the cortical mastoid at 15,
      23 and 32 mm. The various anatomical structures and the relationships between
      them are identified with an operatory logic; this would afford in the surgical
      planning phase a better evaluation of the most appropriate approach, of the risks
      this approach would involve and of the length of the surgical procedure. The
      Authors also studied and developed an accessory that allows the application of
      surgical projection in living patients.

PMID- 7817748
TI  - [Flow-cytometric study of familial paragangliomas of the carotid body].
AB  - Paragangliomas of the carotid body with an autosomal dominant genetic
      transmission have been described in a familial presentation in 7-10% of all the
      cases observed. In less than 10% malignancy is confirmed by secondary metastatic
      localization rather than by typical histological features of malignant diseases,
      such as vascular or perineural invasion, nuclear pleomorphism, mitotic activity.
      The purpose of the study is to present a familial group of paragangliomas of the
      carotid boy and a flow cytometric analysis of tumor content DNA and to discuss
      the prognostic value of the results. The paragangliomas of these related patients
      (father and daughter) are diploid, without regional lymph node or distant
      metastases; clinical and cytometric findings support a good prognosis even if an
      accurate follow up of such neuroendocrine tumors is nonetheless mandatory.
      Considering data in Literature, the Authors also propose a prognostic
      classification of paragangliomas as follows: noninvasive (capsulated, without
      vascular or perineural infiltration, diploid); locally invasive (histological
      signs such as vascular or perineural infiltration, nuclear pleomorphism, abnormal
      mitoses etc, diploid); potentially malignant (histological signs, non-diploid,
      expression of few antigens) and malignant (regional or distant metastases).

PMID- 7817749
TI  - [Cytologic findings on chronic inflammatory disease of the vocal folds].
AB  - The usefulness of cytologic diagnosis in laryngeal pathology is still
      controversial, also in the cytopathologist's opinion. A sampling procedure such
      as routine cytodiagnosis can be considered useful for both diagnosis and
      treatment of non-surgically related laryngeal diseases. This study was designed
      in order to demonstrate how cytodiagnosis can be useful in etiologic and
      pathogenetic diagnosis of chronic non-specific inflammatory diseases of the vocal
      folds. Cytologic sampling was carried out on brushing material of simple and
      hyperplastic laryngeal inflammations and on normal vocarfolds which were used as
      control. Through cytologic examination it was possible to evidence specific
      morphological findings which allowed differentiation of not only healthy from
      diseased vocal cords, but also hyperplastic from simple inflammatory processes.
      Moreover, the high incidence of goblet cells and cylindric squamous metaplasia in
      hyperplastic corditis, as well as the frequent presence of fungal involvement in
      the simple forms, prompted the Authors to hypothesize pathogenetic mechanisms as
      well as progression inducing factors of the pathologies in question.

PMID- 7817751
TI  - [The development of medical education].

PMID- 7817750
TI  - [A rare case of endotympanic hemangioma].
AB  - Hemangiomas affectioning the external ear canal or the tympanic membrane have
      rarely been described. Only a very few cases are reported in world literature
      conarn these vascular tumors involving the middle ear space. The Authors report a
      rare case of a right endotympanic hemangioma associated with ossicular
      dysmorphism, resulting in conductive unilateral hearing loss, in a 9 year-old
      girl with cutaneous hemangiomas of the face. The Authors review Literature and
      discuss the possible pathogenetic implications of the intraoperatory findings.

PMID- 7817752
TI  - [History and epidemiology of specific vasomotor rhinopathy].

PMID- 7817753
TI  - [Recent achievements on biological basis of allergens and neurotransmitters].

PMID- 7817754
TI  - [Vasomotor rhinopathies].

PMID- 7817755
TI  - [Allergic rhinitis on the threshold of the year 2000].

PMID- 7817756
TI  - [Specific vasomotor rhinopathy].

PMID- 7817757
TI  - [Rhinitis and asthma].

PMID- 7817758
TI  - [Rhinobronchial syndrome].

PMID- 7817759
TI  - [Anatomy and physiology of the nose].

PMID- 7817760
TI  - [Out considerations on the etiopathogenesis of nasal-sinus polyposis].

PMID- 7817761
TI  - [Recent progress in instrumental rhinological diagnosis].

PMID- 7817763
TI  - [Recent advancements in the clinical and surgical therapy of allergic rhinitis].

PMID- 7817762
TI  - [The actuality of diagnostic allergologic techniques in otolaryngology].

PMID- 7817764
TI  - [On the topic of local therapy].

PMID- 7817765
TI  - [Synthesis of quinazolino-1,3-benzothiazine derivatives].
AB  - The ring-closure reactions of N-(3,4-dimethoxyphenylthio-methyl)-2-nitrobenzamide
      derivatives 5a,b with phosphoryl chloride gave 4-(2'-nitrophenyl)-2H-1,3
      benzothiazine derivatives 7a,b, which on reduction yielded 4-(2'-aminophenyl)-3,4
      dihydro-2H-1,3-benzothiazines 8a,b. Reaction of these compounds with phosgene led
      to the derivatives 9a,b of a new heterocyclic ring system, 6H,8H-quinazolino[3,4
      c] [1,3]benzothiazine. The structures of the title compounds were proved by their
      ir and nmr (1H, 13C) spectra.

PMID- 7817766
TI  - [Synthesis of tert-butylcyclopentane-fused 1,3-oxazines and 1,3-thiazines].
AB  - Chlorosulphonyl isocyanate (CSI) addition to 4-tert-butylcyclopentene furnished
      the azetidinone (3) in a stereospecific reaction. Azetidinone 3 was transformed
      by ring opening esterification and lithium aluminium hydride (LAH) reduction to
      the 2-hydroxy-methyl-4-tert-butyl-1-cyclopentylamine (6). The N-methyl
      aminoalcohol (8) was prepared from amino esters (5) with ethyl chloroformate and
      subsequent LAH reduction. By different ring-closure methods, a number of tert
      butyl-cyclopentante-fused 1,3-oxazines and 1,3-thiazines were synthesized. A
      comparative study of the prepared compounds was performed by IR, 1H- and 13C-NMR,
      DEPT and DNOE measurements.

PMID- 7817767
TI  - [Preparation and steric structure of condensed-skeleton saturated diphenyl
      substituted isoindolones].
AB  - The Friedel-Crafts reaction of benzene with cis-4-cyclohexene-1,2-dicarboxylic
      anhydride (1) yields trans-5-phenyl-cis-2-benzoylcyclohexanecarboxylic acid (2),
      which gave cyclohexane-condensed pyridazinone (3) with hydrazine, and cis-4,5
      tetramethylene-1,2-oxazin-8-one (4) with hydroxylamine. From 2 with
      ethylenediamine, the saturated imidazol[2,3-a]iso-indolone (5) was prepared,
      while the reaction of 2 with 1,3-diaminopropane furnished a mixture of two
      isomeric pyrimido[2,3-a]isoindolones (6a,b) in the relative positions of the
      benzene ring and cyclohexane annelation hydrogens. From the reaction of 2 with 3
      aminopropanol, the oxazino[2,3-a]isoindolone (7) was obtained. The reaction of 2
      with cis-2-hydroxymethylcyclohexylamine gave the tetracyclic (8), while 2 and
      diendo-3-hydroxymethylbicyclo[2.2.1]hept-5-enyl-2-amine yielded the isomers
      (9a,b), which differ in the mutual positions of the phenyl group on the
      quaternary carbon and cyclohexane annelation hydrogens. 1H and 13C-nmr spectra
      and DNOE and 2D-HSC measurements proved that the 5-phenyl group is cis-equatorial
      to the two annelated hydrogens of the cyclohexane ring.

PMID- 7817768
TI  - Study of local anaesthetics: Part 124. Influence of the ointment bases on the
      liberation of pentacaine chloride and heptacaine chloride.
AB  - The aim of the study was to choose a suitable base for the topical application of
      pentacaine chloride and heptacaine chloride. Both local anaesthetics were
      processed into two hydrophilic creams, two hydrophobic creams and one hydrophobic
      ointment as well as into three hydrogel bases. The assumption that the rate of
      the release of both local anaesthetics from hydrogel bases is greater than from
      cream bases has been fully confirmed.

PMID- 7817769
TI  - [In vitro inhibitory effects of 16-methyl-substituted steroids on 5 alpha
      reductase in rat and human prostates].
AB  - The inhibitory effects (IC50) of 16-methyl steroids on 5 alpha-reductase were
      studied. The in vitro experiments were carried out with homogenates of rat and
      human prostates. The investigated 16-methyl steroids were found to be weak
      inhibitors. In comparison with the known 5 alpha-reductase inhibitor 4-MA, the
      relative IC50 values of the studied compounds are 4.7 times or more greater than
      4-MA in human prostate and 23.5 times or more greater than 4-MA in rat prostate.
      The IC50 values increase in the sequence 16 alpha, 16-beta- and 16,16-dimethyl
      derivatives. In human prostate homogenates IC50 varies between 0.6 and 120, while
      in rat it ranges from 1.6 to 1000 microM. This shows that the enzyme of the human
      prostate is more sensitive than that of the rat prostate to the methyl
      substituted compounds. Acylation of the 17-hydroxy group significantly increases
      the IC50 values (cf. 8,11: from 4.8 to 23.5 and from 0.52 to 0.62;9,12: from 26.0
      to 170.0 and from 0.58 to 1.4;15,17: from 3.9 to 35.0; and 16,18: from 5.6 to
      58.0 microM). Whereas lack of a 19-CH3 group improves the inhibitory effect in
      the 16-unsubstituted compounds (1,19;14,22), the reverse hold in the 16
      methylated derivatives (9,20; 10,21; 15,23; 16,24).

PMID- 7817770
TI  - [Solution kinetics of magnesium oxide containing granules produced by laboratory
      scale fluidization].
AB  - In practice of manufacturing industrial pharmaceutical products, the technique of
      fluidization has been used extensively in the past decades. The authors studied
      the magnesium oxide-containing granulates made by fluidization granulation in
      laboratory, to optimize the process, to determine the neutralization kinetic
      parameters of granulates, to establish the connections between the method of
      granulation and the release of active substances. According to our findings, the
      pharmaceutical product's characteristics in the aspects of physics, chemistry,
      stability and bioavailability may remarkably change without fixing the border
      conditions of parameters within limits.

PMID- 7817771
TI  - Characteristics of partially purified prolidase and prolinase from the human
      prostate.
AB  - Both prolidase and prolinase from the human prostate were separated into two
      peaks by TSK DEAE-5PW chromatography. These peaks of prolidase isozymes I and II
      differed from each other in their responses to preincubation with Mn2+, their
      substrate specificity, optimal pH, and heat stability. The molecular weights of
      prolidases I and II were estimated to be 110,000 and 165,000, respectively, by
      gel filtration. Substrate specificity of prolinase peaks I and II was almost the
      same, but they differed in optimal pH and heat stability. The molecular weights
      of prolinases I and II were about 85,000 and 63,000, respectively. These results
      indicate that two isozymes of prolidase and of prolinase, which differ in various
      characteristics, are present in the human prostate.

PMID- 7817772
TI  - Impaired interleukin-8-dependent chemotaxis by synovial fluid polymorphonuclear
      leukocytes in rheumatoid arthritis.
AB  - The accumulation of polymorphonuclear leukocytes (PMN) in synovial fluid is a
      common feature of rheumatoid arthritis (RA). We studied the chemotactic response
      of PMN obtained from the synovial fluid and from the peripheral blood of patients
      with RA using a modified Boyden's method, in which interleukin-8 (IL-8) or N
      formyl-methionyl-leucyl-phenylalanine (FMLP) was used as a chemotactic agent. The
      IL-8-induced response of peripheral blood PMN from 15 patients with RA did not
      differ from that of 15 healthy controls. A decreased chemotactic response to IL-8
      was, however, observed in PMN from the synovial fluid of 12 patients with RA
      compared with peripheral blood cells of the same individual. This defective
      chemotactic ability of PMN was inversely correlated with the number of
      infiltrating cells in the synovial fluid. We also obtained similar results with
      FMLP. These results indicate that the chemotactic ability of PMN may be reduced
      after migrating to the synovial fluid.

PMID- 7817773
TI  - Application of polymerase chain reaction (PCR) to the microscopically identified
      cells on the slides: evaluation of specificity and sensitivity of single cell
      PCR.
AB  - The sensitivity and specificity of single cell polymerase chain reaction (PCR)
      were studied. Its high sensitivity enabled detection of a single-copy gene, such
      as human T-lymphotropic virus type I genome in paraffin sections. The rate of
      obtaining positive signals with this method was affected by the number of copies
      of the gene in the target cell. Specificity was satisfactory if the procedure was
      properly and carefully followed. Since the single cell PCR is a time-consuming
      method which requires skill and experience to pick up the target cells
      accurately, the applicability of this method is limited. It works best when it is
      used to analyze a single or a few copy genes in histologically identified cells.

PMID- 7817774
TI  - The occurrence of neurons with strongly negatively charged surface coats in
      mammalian, avian, reptilian, amphibian and piscine brains.
AB  - Neurons with strongly negatively charged surface coats were recognized in
      mammalian, avian, reptilian, amphibian and piscine brains. Many large-sized
      neurons had strongly negatively charged surface coats in the visual cortex and
      brain stem of the cow, cat, guinea pig, mouse, quail and parakeet. Such neurons
      were also seen in the brain stem of the lower vertebrates such as the house
      lizard, Japanese terrapin, bullfrog, newt, carp and sweetfish.

PMID- 7817775
TI  - Evaluation of renal function by dynamic MR imaging: effect of water load.
AB  - The aim of this study was to investigate the usefulness of magnetic resonance
      (MR) imaging in the evaluation of renal function, with particular attention to
      the effects of water load. Ten healthy volunteers underwent dynamic MR imaging
      after an injection of gadolinium diethylene-triaminepenta-acetic acid (Gd-DTPA)
      as a contrast agent to evaluate renal function by the following four methods: the
      positive method [longitudinal relaxation time (T1) shortening is the dominant
      effect], the negative method [transverse relaxation time (T2) shortening is the
      dominant effect] and two intermediate methods by switching the Gd-DTPA
      concentrations used in the positive and negative methods. A prolonged cortical
      peak time and a reduced medullary peak level were observed by the positive method
      under a dehydrated condition, suggesting that these variables were slightly
      influenced by Gd-DTPA concentrated in the medulla. By the negative method, low
      signals due to T2* (T2* is the effective transverse relaxation time, typically
      shorter than T2) shortening appeared in the medulla under normal conditions, but
      these signals were unclear when the subject was under an overhydrated condition.
      These results indicate that water metabolism, in addition to imaging parameters
      and Gd-DTPA dose levels, should be considered when renal function is evaluated by
      dynamic MR imaging. Analysis of both the pattern of MR images and the time-signal
      intensity curves may be useful in the evaluation of renal function. The results
      also indicate that the positive method is preferred when the patient is
      overhydrated as it allows the evaluation of the local renal kinetic function by
      recording changes in the regional contrast agent levels.

PMID- 7817776
TI  - A new capacitive heating applicator for the simultaneous radiohyperthermotherapy
      of superficial and shallow-seated tumors.
AB  - External capacitive heating is the usual method of electromagnetic wave heating,
      in which the tumor is caught and heated between two opposite applicators. Using a
      phantom, the authors developed and evaluated the performance of a new capacitive
      heating applicator designed for simultaneous radiohyperthermotherapy (SRH) in
      which the electron beam irradiation is provided from above an external capacitive
      heating applicator for the treatment of superficial and shallow-seated tumors.
      The trial applicator was constructed to fulfill the following conditions: 1. use
      of an electrode plate which does not affect the electron beam depth dose, 2. a
      uniform thickness to maintain flatness of the electron beam, and 3. a cooling
      function to prevent damage to normal skin tissue and enhance the therapeutic gain
      factor. This applicator was comprised of a 0.1-mm-thick copper electrode and a 5
      mm-thick cooling chamber. The depth of the 80% dose of the new applicator was 21
      mm with a 9-MeV electron beam and 36mm with a 15-MeV electron beam, which was
      comparable to the effect of a conventional irradiation bolus. The temperature
      distribution produced by the trial applicator was symmetrical on both sides from
      the center of the applicator. The 50% specific absorption rate region was 6.4 cm
      wide at a depth of 1 cm from the phantom surface and 2.8 cm wide at a depth of 3
      cm. There have been no previous reports on the development of an external
      capacitive heating applicator designed for the SRH of superficial and shallow
      seated tumors; this is the first such report.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7817777
TI  - Comparative analysis on the physique and batting records of the players in the
      National Summer High School Baseball Tournaments before and after the adoption of
      metal bats.
AB  - To clarify the influence of the introduction of metal bats on the physique and
      batting records of the players in the National Summer High School Baseball
      Tournaments, a comparative analysis was conducted between height, body weight,
      body-weight ratio (body weight/height), batting average and home run average of
      the best four teams' players (n = 493) and those of the other teams' players (n =
      4,590) in three periods: the period of the use of wooden bats, that of the use of
      both wooden and metal bats and that of the use of metal bats. In the period of
      metal bat use, the mean values of physique of the best four teams' players were
      significantly larger (P < 0.05) and their average number of home runs was
      significantly higher than those of the other teams' players (P < 0.01). The only
      significant differences between the two groups in those indices for each time
      period were for height in the wood and metal/wood periods. This study
      demonstrated that the differences between the home run average and physique,
      including height, body weight and body-weight ratio of the best four teams and
      the rest of the teams were the greatest after the use of metal bats. These
      findings suggest that the importance of the home run average increased and was
      associated with large-size of physique after the use of metal bats in the
      National Summer High School Baseball Tournaments.

PMID- 7817778
TI  - Clinical value of soluble interleukin-2 receptor in infectious complications.
AB  - In this study, we investigated serum-soluble interleukin-2 receptor (sIL-2r) and
      neopterin (NPT) levels in five patients with severe postoperative infections. A
      total of 25 synchronous determinations of sIL-2r and NPT were performed. A marked
      increase in sIL-2r and NPT levels was observed, and the increase in sIL-2r was
      significantly correlated to that of NPT which is a marker of macrophage activity.
      These results suggest that macrophages are involved in the stimulation of sIL-2r
      release, representing a potentially negative biological effect. The results
      indicate that sIL-2r may be a useful indicator of the efficacy of antibiotics and
      of prognosis.

PMID- 7817779
TI  - The importance of family study in the patients with familial adenomatous
      polyposis.
AB  - Familial adenomatous polyposis (FAP) is a well-known autosomal dominant disorder
      characterized by the formation of multiple adenomatous polyps of the colon.
      Gardner's syndrome is a variant of familial polyposis coli, and both can be
      associated with colonic or extracolonic benign and/or malignant tumors. It has
      been widely recognized that an adenocarcinoma of the colon develops in virtually
      all cases, usually at an earlier age, if polyps are left untreated. Families of
      four individuals diagnosed of FAP were surveyed and 56 relatives of the families
      were examined. Of these 56, 21 had multiple colon polyps, 3 of whom had early
      stage adenocarcinomas. We consider that familial survey of FAP individuals can be
      of considerable benefit for this high-risk population due to the autosomal nature
      of the disease, allowing diagnosis of an associated cancer at an earlier stage.

PMID- 7817780
TI  - High gelsolin content of developing oligodendrocytes.
AB  - The actin-binding protein gelsolin that severs and caps the actin microfilaments
      under the control of the cytoplasmic free calcium and the membranous
      phosphatidylinositol 4,5-bisphosphate, is essentially restricted to the
      oligodendroglia in the central nervous system. Immunocytochemistry showed that
      gelsolin is an early marker of oligodendrocytes, both in vivo, in the rat
      cerebellum, and in vitro, in oligodendrocyte culture. We report the early
      appearance of gelsolin in A2B5-positive precursor oligodendrocyte cells and the
      specific expression of gelsolin in OL-1-, GC-, and MBP-positive oligodendrocytes
      in culture. The protein was distributed throughout the cell body and in the
      branched cell processes of cultured oligodendrocytes, but not in the MBP-positive
      membrane sheets. Gelsolin is thus cytosolic and not a myelin component. The
      quantitative study demonstrated that that the cerebellar gelsolin content changes
      significantly with age, with the maximal value at the age of 21 days, confirming
      that large amounts of gelsolin are transiently synthesized during development,
      especially from the first events of myelinogenesis. The results are consistent
      with gelsolin being involved, through its effects on the actin cytoskeleton, in
      the motile events occurring during the growth of the oligodendroglial processes
      towards the axons and the wrapping of the myelin sheaths around the axons.

PMID- 7817781
TI  - Migration behavior of granule cells on laminin in cerebellar microexplant
      cultures from early postnatal reeler mutant mice.
AB  - The behaviors of neuroblasts of granule cell neurons and their precursor cells on
      a poly-L-lysine/laminin substratum were examined in cerebellar microexplant
      cultures from early postnatal reeler mutant and normal mice. The total numbers of
      migrating neuroblasts and their precursor cells or blast cells derived from the
      mutant cerebellum were markedly reduced in comparison with their normal
      counterparts. However, no difference was shown between these two strains in
      either the numbers of blast cells or neuroblasts that migrated from single
      explants. In addition, all behaviors examined, such as migration of neuroblasts
      and the proliferation of blast cells in culture were identical between both
      genotypes. Thus, behaviors of both granule cells and their precursors in the
      cerebellar cortex of reeler mutant mouse may be qualitatively identical to those
      of normal counterparts, but precursors of granule cells in the external germinal
      layer of the cerebellar cortex may be reduced in the reeler mouse.

PMID- 7817782
TI  - The critical period for ethanol effects on cholinergic neuronal expression in
      neuroblast-enriched cultures derived from 3-day-old chick embryo: NGF ameliorates
      the cholinotoxic effects of ethanol.
AB  - Studies from our laboratory have established that ethanol exerts morphological
      and biochemical neurotoxic effects during early neuroembryogenesis in the chick
      brain both in ovo and in culture. In the present study, we further localized the
      critical period for ethanol effects on cholinergic neuronal expression using
      neuroblast-enriched cultures derived from 3-day-old chick embryos. Moreover, we
      report that NGF attenuated the cholinotoxic effects of ethanol. We used the
      following experimental paradigms: cultures treated with ethanol alone either C0
      C3 or C4-C10; NGF alone C0-C4 or C4-C10; ethanol and NGF given concomitantly;
      ethanol given first then replaced with NGF in the medium; or NGF given first then
      replaced with ethanol in the medium. The results revealed: (1) the cholinotoxic
      effect of ethanol occurs between culture days C0 and C4 with day 3 appearing to
      be most critical; (2) similarly, the critical period for the cholinotoxic effects
      of NGF is during early neuroblast differentiation, culture days C0-C4; (3) NGF
      can prevent the cholinotoxic effects of ethanol only if both ethanol and NGF are
      given concomitantly or if ethanol is given first, then culture is replaced with
      NGF-containing medium.

PMID- 7817783
TI  - Interleukin-1 beta and interferon gamma interact with fibroblast growth factor-2
      in the control of neuroblastoma cell proliferation and differentiation.
AB  - Based on our previous observations that neuroblastoma (NB) cells express
      fibroblast growth factor-2 (FGF-2; basic FGF) and respond to it [Janet T. et al.
      (submitted); Wewetzer K. et al. (1993) J. Neurosci. Res. 36, 209-215), we
      attempted to find to what extent selected cytokines [interleukin (IL)-1 beta and
      interferon gamma (IFN gamma)] may modulate FGF-mediated proliferative activity
      and differentiation. The NB cell lines IMR-32, SH-SY5Y, GIMEN and LAN-1 and
      colorimetric assays were used for the determination of cell numbers. IL-1 beta
      (and several other ILs, including IL-1 alpha, -2, -3, and 6) per se did not
      affect proliferation of any cell line studied. IFN gamma inhibited growth of
      GIMEN and LAN-1 cells, but was uneffective on IMR-32 and SH-SY5Y cells. FGF-2 was
      antimitogenic for GIMEN cells. IFN gamma reversed and IL-1 beta enhanced this
      antimitogenic effect of FGF-2. FGF-2 per se did not affect LAN-1 cells and did
      not modulate the growth inhibitory actions of IFN gamma on these cells. FGF-2
      induced proliferation of IMR-32 and SH-SY5Y cells. This effect was not modulated
      by IFN gamma or IL-1 beta. These results suggest a heterogeneous response pattern
      of human NB cell lines towards the cytokines studied and complex interactions of
      FGF-2, IL-1 beta and IFN gamma.

PMID- 7817784
TI  - Persistence of heterotypical synapses in transplanted cerebellar cultures in the
      absence of functional glia.
AB  - Neonatal mouse cerebellar cultures depleted of granule cells and functional glia
      by exposure to cytosine arabinoside were transplanted with either granule cells
      and glia or with granule cells in the absence of functional glia. Myelination was
      evident in cultures transplanted with granule cells and glia, excess sprouted
      cortical neurites were reduced, Purkinje cells acquired astrocytic sheaths and
      had a near normal complement of axosomatic synapses, and homotypical parallel
      fiber-Purkinje cell dendritic spine synapses were present in a 2.4:1 ratio to
      heterotypical recurrent axon collateral-Purkinje cell dendritic spine synapses.
      Cultures transplanted with granule cells were not myelinated, sprouted cortical
      neurites were not reduced. Purkinje cells lacked astrocytic sheaths and their
      somata remained hyperinnervated, and the ratio of homotypical to heterotypical
      dendritic spine synapses was 1.4:1. In the absence of functional glia there was a
      greater persistence of heterotypical recurrent axon collateral-Purkinje cell
      dendritic spine synapses. These results are consistent with a previously
      described astrocytic role in the regulation of axosomatic synapse density on
      glially ensheathed neurons, and suggest astrocytic participation in the reduction
      of heterotypical axospinous synapses. Astrocyte-mediated synapse reduction may be
      an important mechanism for circuit reorganization after transplantation or during
      development.

PMID- 7817785
TI  - Pattern of polyamines and related monoacetyl derivatives in chick embryo retina
      during development.
AB  - Polyamines and related monoacetyl derivatives were studied in chick embryo retina
      during development (6th-19th day). Putrescine, which is high in the first phase
      of retinogenesis, is necessary to sustain both tissue proliferation and via N
      acetylputrescine, gamma-aminobutyric acid synthesis. A later increase in
      spermidine and particularly spermine may play a role in the last phase of
      development when the retina reaches maturation. The presence of N1
      acetylspermidine already at the 8th day indicates that in chick embryo retina,
      putrescine synthesis can depend on two separate pathways. The first involves
      ornithine decarboxylase activity; the second, spermidine/spermine N1
      acetyltransferase and probably polyamine oxidase that converts spermidine to
      putrescine via N1-acetylspermidine.

PMID- 7817786
TI  - Age-dependent changes in the proliferative response of S-100 protein-positive
      glial cells to injury in the rat brain.
AB  - A mechanical injury was inflicted to the left cerebral hemisphere in rats of four
      age groups: newborns, 6, 14 and 30 days old. The injury was followed by
      [3H]thymidine injections at different time intervals. Brain sections were
      immunostained for S-100 protein and subjected to autoradiography. During
      microscopic observations of the injury region, locations and numbers of the
      autoradiographically labeled astrocytes expressing S-100 protein were recorded.
      On the basis of the observations, injury-induced changes in the total number of
      proliferating astrocytes, as well as in their distribution, were analysed
      quantitatively. In rats injured neonatally, as well as those injured on postnatal
      days 6 and 14, the reactive increase in the number of proliferating astrocytes
      began on the first post-traumatic day. In 30-day-old rats the increase was slower
      and appeared on day 2. The maximal increase in the astrocyte proliferative
      activity occurred in 6-day-old rats as early as day 1 after injury and was about
      eight times higher than that recorded in newborns, and nearly twice as high as
      that recorded in brains of 30-day-old rats. The results suggest that the
      intensity of astrocyte proliferative response to injury cannot be regarded as
      simply being proportional to the developmental progress of the brain tissue.
      Rather, these results indicate that changes in glial proliferative responses to
      injury follow a developmental time course, with a peak around the end of the
      first postnatal week.

PMID- 7817787
TI  - Characterization of N-cadherin messenger RNA and polypeptide expression in rat.
AB  - The cell adhesion molecule N-cadherin is a member of the cadherin gene
      superfamily. The protein is involved in morphogenetic processes, including
      neurite extension. In this study, N-cadherin mRNA and polypeptide expression were
      investigated in rat brain, liver, muscle, heart, kidney and lung during postnatal
      development and aging. Six synthetic oligonucleotide probes covering different
      parts of mouse N-cadherin cDNA all hybridized to 5.2, 4.3-4.4 and 3.5 kb mRNAs in
      rat tissues. The mRNA pattern differed between tissues and, furthermore, the
      amount of N-cadherin mRNA and polypeptides in brain, liver and heart was higher
      than in muscle, kidney and lung. N-cadherin expression decreased slightly during
      early postnatal development in all tissues, whereas no changes in N-cadherin
      expression were observed during aging. Antibodies against a fusion protein
      containing the transmembrane and cytoplasmic sequence of chick N-cadherin were
      produced. These antibodies, termed anti-N-cad-cyt, were compared to the R-156
      antibodies which recognize the 24 C-terminal amino acids of N-cadherin and which
      have been shown to react with a broad spectrum of cadherins. Using these two
      antibodies, it was shown that the 130 kDa N-cadherin polypeptide was subject to
      calcium-dependent cleavage of the cytoplasmic domain. Conversely, in the absence
      of calcium the polypeptide was cleaved extracellularly, producing two C-terminal
      fragments of 85 and 95 kDa. A 122 kDa polypeptide was recognized by both
      antibodies and may be either an alternatively spliced form of N-cadherin or a
      closely related cadherin.

PMID- 7817788
TI  - The effect of influenza C virus on the Purkinje cells of chick embryo cerebellum.
AB  - Intra-amniotic inoculation of influenza C virus resulted in observable and
      quantitatively measurable changes in the Purkinje cells of chick embryo
      cerebellum. Purkinje cells were visualized by the Golgi-Cox procedure and
      prepared for statistical and computer evaluation from camera lucida drawings.
      Four computer-generated measurements (the area of the dendritic arbor, the
      perimeter of the dendritic tree, and the height and width of the cell's
      arborization) and two manually counted measurements (total number of branches and
      the number of first order branches) were made. Analysis of Purkinje cells from
      influenza C virus-infected embryos showed disturbances in dendritic arborization
      patterns and misalignment in the arrangement of the cells in the Purkinje cell
      layer compared to control cells. Statistical evaluation of Purkinje cell
      arborization showed significant decreases in all measured parameters for the
      influenza C virus-infected members when compared with the members of the
      uninfected control group.

PMID- 7817789
TI  - Effects of early chronic diazepam treatment on incorporation of glucose and beta
      hydroxybutyrate into cerebral amino acids: relation to undernutrition.
AB  - The effects of early chronic diazepam (DZP) exposure on blood glucose and ketone
      body concentration and glucose and beta-hydroxybutyrate (beta HB) utilization for
      regional cerebral amino acid biosynthesis were studied in suckling rats. The
      animals were treated from postnatal day 2 (P2) to 21 (P21) by a daily
      subcutaneous injection of 10 mg/kg DZP or of the dissolution vehicle and studied
      at P5, P10, P14 and P21, together with an additional group of food-restricted
      rats obtained by an increase in litter size. DZP treatment induced a 9-26%
      decrease in body and brain weight. Undernutrition decreased body weight by 20-24%
      at all ages whereas brain weight was relatively spared. DZP and N
      desmethyldiazepam concentrations decreased with age and were cleared from brain
      and plasma by 6-8 hrs after the injection. DZP decreased plasma glucose
      concentrations by 6-12% at P5, P14 and P21, whereas undernutrition did not change
      plasma glucose concentrations, except for a 7% decrease at P14. DZP treatment had
      no consequences on circulating concentrations of both ketone bodies while
      undernutrition increased their concentration by 45-362% at all ages. The
      conversion of [14C]glucose into cerebral amino acids was reduced by DZP at P5 and
      P10. The cerebral concentration of neurotransmitter amino acids was not affected
      by DZP treatment which only increased the amount of neutral amino acids mainly in
      the cerebellum at P5 and P10. After [U-14C]glucose injection, specific
      radioactivities of cerebral amino acids were mostly decreased by DZP from P5 to
      P14 and significantly increased at P21. With [3-14C] beta HB as a precursor,
      specific radioactivities of neurotransmitter amino acids were increased by DZP.
      In conclusion, P5 and P10 rats appear to be most sensitive to DZP effects whereas
      some tolerance to the drug seems to develop by P21. The lack of effects of DZP on
      blood ketone body concentrations compared to food restriction as well as the
      relative sparing of brain weight in undernourished rats confirms that the
      cerebral metabolic consequences of early DZP exposure on brain energy metabolism
      are mostly direct effects not mediated by sedation-induced undernutrition.

PMID- 7817790
TI  - Biochemical properties of Na+/K(+)-ATPase in axonal growth cone particles
      isolated from fetal rat brain.
AB  - Axonal growth cones (AGC) isolated from fetal rat brain have an important
      specific activity of N+/K(+)-ATPase. Kinetic assays of the enzyme in AGC showed
      that Km values for ATP or K+ are similar to those reported for the adult brain
      enzyme. For Na+ the affinity (Km) was lower. Vmax for the three substrates was
      several times lower in AGC as compared to the adult value. We also observed two
      apparent inhibition constants of Na+/K(+)-ATPase by ouabain, one of low affinity,
      possibly corresponding to the alpha 1 isoform and another of high affinity which
      is different to that described for the alpha 2 isoform of the enzyme. These
      results support an important role for the sodium pump in the maintainance of
      volume and cationic balance in neuronal differentiating structures. The
      functional differences observed also suggest that the enzymatic complex of
      Na+/K(+)-ATPase in AGC is in a transitional state towards the adult
      configuration.

PMID- 7817791
TI  - Characterization of sodium-independent beta-alanine binding to cerebral cortical
      membranes from 7-day-old and adult mice.
AB  - The sodium-independent binding of beta-alanine to cerebral cortical membranes
      from adult (3- and 12-month-old) and developing (7-day-old) mice was
      characterized for the first time. The binding was saturable in each age group,
      consisting of only one component. The affinity for beta-alanine was highest and
      the number of available binding sites greatest in young animals. The binding was
      not affected by strychnine, but inhibited by beta-alanine itself, glycine, L
      alanine and L-serine, the IC50 values being lower in immature mice. Glycine was
      shown to be a competitive inhibitor. The binding was also inhibited, albeit only
      in adults, by N-methyl-D-aspartate receptor antagonists acting at the glycine
      modulatory site and by some GABAergic substances. It is concluded that even
      though beta-alanine may possess binding sites of its own, particularly in the
      immature cerebral cortex, beta-alanine could at least partly bind to strychnine
      insensitive glycine sites in the N-methyl-D-aspartate receptor complex.

PMID- 7817792
TI  - Immunocytochemical detection of serotonin content in raphe neurons of newborn and
      young adult rabbits before and after acute hypoxia.
AB  - The present immunocytochemical study demonstrates serotonin (5-HT) depletion in
      the dorsal raphe nucleus (DRN) of 3- and 21-day-old rabbits following exposure to
      mild (10% ambient partial pressure of oxygen) and severe hypoxia (5% ambient
      oxygen). Under the mild hypoxic condition, 5-HT immunoreactivity in cells and
      fibers of the DRN was decreased in 3-day-old as well as 21-day-old rabbits, as
      indicated by decreased intensity of the staining compared to age-matched
      controls. Although this decrease was more pronounced in the younger animals,
      recovery from mild hypoxia was seen in both age groups. Hypoxic effects were more
      striking in 3-day-old animals under the severe hypoxic condition, indicating a
      greater depletion of 5-HT than in the mildly hypoxic condition. However, little
      additional effect on the older age group was seen. Further, a decreased ability
      of the 3-day-old rabbits to recover following severe hypoxia suggests that
      protracted effects on the developing serotonergic system occur following severe
      hypoxia during the neonatal period. This was demonstrated by the long-lasting
      decrease in the number of stained cells and fibers of the DRN 4-hr after return
      to normal conditions (21% O2). We conclude that newborns have a decreased rate of
      5-HT synthesis and/or metabolic turnover that results in rapid depletion of
      intracellular stores and protracted time to recover from a hypoxic challenge.
      Similar effects could occur in human fetuses, newborns or infants following birth
      trauma, apnea or other events associated with severe hypoxia.

PMID- 7817793
TI  - Stimulatory effect of opioid peptides and naloxone on rat spinal cord cells in
      primary dissociated culture.
AB  - Opioid peptides leu-enkephalin, a synthetic analog of enkephalin dalargin and an
      opiate receptor blocker naloxone were studied for their morphological effect on
      the cells of dissociated cultures of rat spinal cord. Low density seeding of
      cells (3.10(5);6.10(5) cells/ml) on collagen substrate was performed to document
      that opioid peptides increase the number of cultured cells and neurite outgrowth
      and lead to the activation of the initiated processes of aggregate formation.
      Upon higher density of plating (5.10(6) cells/ml) with poly-L-lysine as a
      substrate, activation of the aggregate formation process was demonstrated, both
      opioid peptides and naloxone leading to an increase in the size of aggregates.
      Statistical treatment of the results obtained in this set of experiments
      documented that leu-enkephalin, dalargin and naloxone increased 2.2-, 2.2-2.6-,
      2.4-fold, respectively, the size of aggregates compared to the control, i.e. the
      reaction of spinal cord cells to opioid peptides and opiate receptor blocker
      naloxon was unidirected. The total effect of opioid peptides and naloxon resulted
      in a 3.6-fold increase in the size of the aggregates compared to the control. The
      data obtained in this study allow the assumption that opioid peptides and
      naloxone, while activating spinal cord cells via receptors of a different type,
      manifest the properties of factors thus increasing survival and adhesion of
      spinal cord cells in culture.

PMID- 7817794
TI  - Acute effects of capsaicin on the postnatal spiral ganglion.
AB  - Capsaicin exerts both excitatory and desensitizing effects on a subset of sensory
      neurons during development in the dorsal root ganglion, but it is not known how
      widespread these effects are in other sensory ganglia especially those not known
      to have any pain sensitivity. The capsaicin sensitivity of auditory neurons in
      the spiral ganglion was investigated in acute preparations from three postnatal
      age groups in the hamster: postnatal days 6-8 (group 1), postnatal days 13-15
      (group 2) and postnatal days 20-22 (group 3). Morphologically, capsaicin altered
      the shape, size, and staining characteristics of spiral ganglion cells (SGCs)
      across all age groups and this effect was apparently not selective for any
      identifiable subpopulation. However, SGCs from the youngest age groups were
      particularly sensitive to capsaicin neurotoxicity. When incubated in media that
      contained cobalt, capsaicin stimulated cobalt uptake within SGCs. KCl
      depolarization was able to produce the same level of cobalt uptake as capsaicin
      treatment. Our data suggest that the extent of capsaicin neurotoxicity in the
      spiral ganglion is strongly age dependent, involves the entry of calcium ions and
      is relatively nonspecific.

PMID- 7817795
TI  - Universal standardization for dual x-ray absorptiometry: patient and phantom
      cross-calibration results.
AB  - The comparison of patient data among different dual x-ray absorptiometry (DXA)
      scanners is complicated because no universally accepted cross-calibration
      procedure or standard currently exists. This study was performed under the
      auspices of the International DXA Standardization Committee to establish
      appropriate cross-calibration parameters. Posteroanterior (PA) lumbar spine
      measurements of 100 women, ages 20-80 years (mean 52.6 +/- 16, range of BMD = 0.4
      1.6 g/cm2) were obtained on a Norland XR26 Mark II, a Lunar DPX-L, and a Hologic
      QDR 2000 densitometer using standard procedures (pencil beam mode for all three
      scanners). Area, BMC, and BMD results from the different scanners were compared
      for all patients. In addition, the European spine phantom (ESP) and the European
      spine phantom prototype (ESP prototype), as well as standard phantoms from all
      three manufacturers, were evaluated on the three systems. To achieve universal
      scanner calibration, we used the intercept and slope of the patient's
      correlations and the value of the middle vertebra of the ESP as a reference point
      in a series of standardization formulas, and we have expressed the results as
      sBMD (mg/cm2). The correlations of the patients' spinal BMD values were excellent
      for each of the three scanner pairs. The average absolute difference in patient
      spinal BMD values (L2-4) between Hologic and Norland was 0.012 g/cm2 (1.3%); it
      was 0.113 g/cm2 (11.7%) between Hologic and Lunar and 0.118 g/cm2 (12.2%) between
      Norland and Lunar. The phantoms' regression lines approximated those of the
      patient regression lines, and the phantoms with only one measurement point were
      very close to the patients' regression lines. After applying the standardization
      formulas, the average absolute differences for the 100 patients were 28 mg/cm2
      (2.7%) for Hologic/Norland, 23 mg/cm2 (2.2%) for Hologic/Lunar, and 29 mg/cm2
      (2.8%) for Norland/Lunar. Average BMD results for the patients before correction
      were 0.972 mg/cm2 for Hologic, 1.100 g/cm2 for Lunar, and 0.969 g/cm2 for
      Norland. After correction, sBMD results for patients were 1045 mg/cm2 for
      Hologic, 1047 mg/cm2 for Lunar, and 1043 mg/cm2 for Norland. The standardization
      approach as performed in our study provided compatibility of DXA results obtained
      on different scanners.

PMID- 7817796
TI  - The bone-remodeling transient: implications for the interpretation of clinical
      studies of bone mass change.
AB  - A computer simulation of the bone-remodeling transient is described, in which the
      focus is explicitly on changes in clinically measurable bone mass (or density).
      Based upon quantitative remodeling data accumulated by histomorphometry and
      calcium tracer kinetics, the simulation shows that much of the apparent gain in
      bone produced by several agents currently employed to treat osteoporosis can be
      explained as a remodeling transient rather than as a fundamental alteration of
      remodeling balance. Even gains as large as 30% or more can be produced by nothing
      more than the remodeling transient under certain plausible combinations of basal
      remodeling rate, remodeling period, and degree of bone loss. The simulation
      further highlights the importance, in evaluating bone-active agents, of
      separating the response across the first remodeling period from bone changes that
      may ensue thereafter.

PMID- 7817797
TI  - Low bone mass in idiopathic renal stone formers: magnitude and significance.
AB  - To assess bone mineral density (BMD) in idiopathic calcium nephrolithiasis, dual
      energy x-ray absorptiometry was performed at lumbar spine, upper femur (femoral
      neck, Ward's triangle, and total area), distal tibial diaphysis, and distal
      tibial epiphysis in 110 male idiopathic calcium stone formers (ICSF); 49 with and
      61 without hypercalciuria on free-choice diet). Results were compared with those
      obtained in 234 healthy male controls, using (1) noncorrected BMD, (2) BMD
      corrected for age, height, and BMI, and (3) a skeletal score based on a tercile
      distribution of BMD values at following four sites: lumbar spine, Ward's
      triangle, tibial diaphysis, and tibial epiphysis. After correction, BMD--and
      therefore also skeletal score--tended to be lower in the stone formers than in
      controls at five of the six measurement sites, that is, lumbar spine, upper
      femur, Ward's triangle, tibial diaphysis, and tibial epiphysis, limit of
      significance being reached for the last two sites without difference between
      hypercalciuric (HCSF) and normocalciuric stone formers (NCSF). Estimated current
      daily calcium intake was significantly lower in patients (616 +/- 499 mg/24 h,
      mean +/- SEM) than in controls (773 +/- 532, p = 0.02). Of 17 patients who in the
      past had received a low-calcium diet for at least 1 year, 10 had a low skeletal
      score (4-6) whereas only 1 had a high score (10-12; p = 0.037). Of the 12 stone
      formers in the study with skeletal score 4 (i.e., the lowest), 8 had experienced
      in the past one or more fractures of any kind versus only 19 of the remaining 77
      patients with skeletal score 5-12 (p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7817798
TI  - Interleukin-4 inhibits spontaneous and parathyroid hormone-related protein
      stimulated osteoclast formation in mice.
AB  - We examined the in vivo effects of recombinant murine IL-4 (rmIL-4) on
      spontaneous and stimulated mouse osteoclast formation. EC-GI cells, which produce
      PThrP and IL-1 alpha, were explanted in nude mice. These EC-GI cell-bearing nude
      mice developed hypercalcemia (4.90 +/- 0.68 mM), and the calcium levels were
      decreased to near normal (3.48 +/- 0.73 mM, p < 0.05) at day 3 by continuous
      infusion of rmIL-4 at a dose of 7 micrograms/day. When infused with 0.6 nmol/day
      of PTHrP(1-34) in ICR mice, rmIL-4 at a dose of 1 or 5 micrograms/day for 3 days
      caused a marked inhibitory effect on hypercalcemia induced by PTHrP(1-34) (3.73
      +/- 0.56-2.54 +/- 0.14 mM, p < 0.01). However, rmIL-4 alone did not change the
      serum calcium in mice. Histomorphometric analysis revealed that rmIL-4 inhibits
      both spontaneous and PTHrP(1-34)-stimulated osteoclast formation in mice, with a
      decrease in osteoclastic surface and in the number of osteoclasts per mm bone
      surface, respectively. We conclude that IL-4 inhibits spontaneous and stimulated
      bone resorption resulting from inhibition of osteoclast formation and modulates
      the development of humoral hypercalcemia of malignancy.

PMID- 7817799
TI  - Abnormal bone mineralization after fluoride treatment in osteoporosis: a small
      angle x-ray-scattering study.
AB  - Sodium fluoride treatment of osteoporosis is known to stimulate bone formation
      and to increase bone mass, but recent clinical trials failed to prove its
      antifracture effectiveness. The formation of bone with abnormal structure and,
      therefore, increased fragility is discussed as a possible explanation. Until now,
      however, exact information on the mineral structure of osteoporotic bone after
      fluoride treatment has been lacking. Bone biopsies were taken from three patients
      with postmenopausal osteoporosis before and after fluoride treatment (60 mg
      NaF/day for 1-2 years), from one patient with iatrogenic fluorosis, as well as
      from three normal controls. The mineral in these samples was investigated by a
      combination of backscattered electron imaging and small-angle x-ray scattering.
      Depending on the total dose of fluoride, an increasing amount of new bone is laid
      down on the surface of preexisting trabeculae. Its mineral structure is identical
      to that of heavy fluorosis and is characterized by the presence of additional
      large crystals, presumably located outside the collagen fibrils. These large
      crystals, which are not present in the controls or in osteoporotic bone before
      fluoride treatment, contribute to increase the mineral density without
      significantly improving the biomechanical properties of the bone. The possible
      success of fluoride treatment depends not only on the amount of newly formed bone
      but also on the rate of bone turnover. Indeed, as soon as significant amounts of
      fluoride are present, bone turnover leads to the replacement of old (normal) bone
      by new (pathologically mineralized) bone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7817800
TI  - Localization of the mRNA for bone matrix proteins during fracture healing as
      determined by in situ hybridization.
AB  - The expression of the mRNAs for osteonectin (ON), osteopontin (OPN), osteocalcin
      (OC), and matrix Gla protein (MGP) was studied by in situ hybridization during
      the healing process of an experimental fracture in adult rat femora. At day 1
      postoperatively, ON mRNA was detected in the proliferating periosteum. At day 3,
      ON, OPN, and OC mRNAs were detected in woven bone. From day 5, MGP and ON mRNAs
      were detected in the immature chondrocytes. From day 7, ON, OPN, and OC mRNAs
      were detected in the osteoblastic cells in newly formed endosteal trabecular
      bone. OPN mRNA was also detected in some of the osteocytes in trabecular bone.
      From day 14, OPN and MGP mRNAs were detected in newly formed periosteal
      hypertrophic chondrocytes, and the ON, OPN, and OC mRNAs were detected in
      osteoblastic cells in newly formed periosteal trabecular bone. Although the cell
      types that expressed each mRNA in fractured bones were similar to those in
      embryonic bones, the time course of these mRNA expression in fractured bones was
      different from that in embryonic bones. We considered that this system is useful
      to investigate the phenotypic change in osteogenic and chondrogenic lineage cells
      that appears during fracture healing at the molecular level.

PMID- 7817801
TI  - Exercise can provide protection against bone loss and prevent the decrease in
      mechanical strength of femoral neck in ovariectomized rats.
AB  - The effect of treadmill exercise on bone loss in ovariectomized (OVX) rats was
      studied in two different sets of experiments. In the first experiment rats were
      either ovariectomized (n = 38) or sham operated (n = 18) at the age of 12 weeks.
      Half the OVX rats were trained twice a day for 30 minutes by running at 10
      m/minute for 7 or 17 weeks. In the second experiment 40 female rats, aged 12
      weeks, were divided into five groups (n = 8). One group of rats was sacrificed on
      day 0 for the baseline data. Other rats were sham operated or ovariectomized for
      9 weeks. Half of both groups were trained using the same training program as in
      the first experiment. OVX reduced trabecular bone volume (TBV) in the distal
      femur to 42.7 and 48.3% in 8 and 18 weeks, respectively. Exercise opposed this
      effect significantly but could not prevent it totally. Exercise did not have any
      significant effect on sham-operated animals. OVX induced a 17.7 and 30.7%
      decrease in maximal failure load of femoral neck in 8 and 18 weeks, respectively.
      A corresponding decrease was also observed in the torque capacity of tibia.
      Exercise was able to prevent almost totally the decrease in bone strength of
      femoral neck, tibia, and humerus. In conclusion, our results suggest that the
      measurement of bone strength in aging female rat femoral neck can be used as a
      useful indicator of the deleterious effect of OVX in bone. These results further
      indicate that exercise can overcome a significant part of the decrease in
      trabecular bone volume and maintain the mechanical strength of femoral neck and
      tibial shaft in the OVX rats.

PMID- 7817802
TI  - Identification of osteocalcin mRNA in nonosteoid tissue of rats and humans by
      reverse transcription-polymerase chain reaction.
AB  - Diseased or necrotic tissue can become calcified in a way that resembles bone. We
      examined soft tissues for the presence and regulation of the mRNA for the bone
      associated protein, osteocalcin (OC). RNA was isolated from liver, kidney, lung,
      brain, muscle, and bone of young (2 months) male SD rats and analyzed for beta
      actin, IGF-I, metallothionein IIa, alpha 1 collagen, calbindin-D9k (CaBP), and OC
      mRNA by reverse transcription-polymerase chain reaction (RT-PCR). All PCR
      products but CaBP were found in bone; CaBP was present only in duodenum, kidney,
      and lung. OC product was detected in all tissues; the identity of the PCR product
      was confirmed by sequencing. Bone OC mRNA levels were calculated to be 1000-fold
      higher than duodenal levels. Rats fed a 0.8% strontium diet for 7 days to drive
      down serum 1,25-dihydroxyvitamin D3 levels [1,25(OH)2D3] and then injected with
      300 ng 1,25(OH)2D3/100 body weight had increased duodenal CaBP (2.5-fold) and
      femur OC mRNA (2.2-fold) 24 h after treatment. Duodenal OC mRNA was unchanged. OC
      mRNA was found in nondiseased human aortae, and the amount of message was
      elevated in calcified aorta and calcified aortic plaques. These results
      demonstrate that (1) tissues other than bone have low basal expression of OC
      mRNA, (2) OC mRNA is not regulated by vitamin D in nonosteoid tissue, and (3)
      expression of OC mRNA in atherosclerotic aorta reflects a role for bone-forming
      cells in ectopic bone formation observed in certain disease conditions.

PMID- 7817803
TI  - Bafilomycin A1 inhibits bone resorption and tooth eruption in vivo.
AB  - It has been shown that a specific inhibitor of vacuolar H(+)-ATPases, bafilomycin
      A1, inhibits bone resorption by isolated chicken osteoclasts by blocking the
      proton pump in the ruffled border membrane. We report here the effects of
      bafilomycin A1 on bone resorption in vivo. Using a cannulated osmotic minipump
      delivery system, we infused bafilomycin locally to the eruption pathway of
      permanent premolars of beagle dogs. We used pit formation by osteoclasts in vitro
      to estimate the concentrations and heat stability of bafilomycin to be used in
      vivo. In this model, osteoclasts were cultured on thin bone slices, in which they
      form pits indicative of resorption. After 2 weeks preincubation at 37 degrees C,
      bafilomycin concentrations of 10(-6) and 10(-7) M but not 10(-8) M completely
      inhibited the resorptive activity of cultured osteoclasts, and the two larger
      doses were chosen for use in vivo. Local delivery of 10(-6) M bafilomycin to the
      eruption pathway of the fourth permanent mandibular premolar during mideruption
      inhibited tooth eruption by blocking bone resorption as assayed by radiography,
      light microscopy, and scanning electron microscopy. Bafilomycin at 10(-7) M had
      similar but less intensive effects. Moreover, osteoclasts in the alveolar bone of
      crypts treated with 10(-7) M bafilomycin A1 stained very weakly for tartrate
      resistant acid phosphatase. The effect of bafilomycin on bone resorption was
      shown to be very local, and no side effects of treatment with bafilomycin were
      observed in adjacent teeth or the behavior of dogs. We report here, for the first
      time, inhibition of tooth eruption caused by inhibited bone resorption using
      bafilomycin A1 in vivo.

PMID- 7817805
TI  - Serum undercarboxylated osteocalcin correlates with hip bone mineral density in
      elderly women.
AB  - We previously showed that circulating undercarboxylated osteocalcin (ucOC) is
      elevated in elderly women and is a powerful marker of the subsequent risk of hip
      fracture in elderly institutionalized women (J Clin Invest 1993; 91:1769). To
      investigate the relationship between bone mass and ucOC, we measured bone mineral
      density (BMD) of the hip with dual-energy x-ray absorptiometry in 98 elderly
      institutionalized women, 81.4 +/- 6.0 years old. ucOC was negatively correlated
      with BMD at all sites (r = -0.26 to -0.38, p < 0.001 to p < 0.0001), even after
      exclusion of the effect of age by partial correlation (for the femoral neck, r = 
      0.26, p < 0.01) and after controlling for serum parathyroid hormone. BMD was
      significantly lower at all sites of measurement in women with elevated ucOC (>
      1.65 ng/ml, upper limit of the normal range in young women) than in those with
      normal ucOC (for the neck, 0.58 +/- 0.13 versus 0.43 +/- 0.13 g/cm2, p < 0.001).
      Similar results were obtained for ucOC expressed as the fraction of total OC
      (ucOC%). Multiple regression showed that ucOC has the highest predictive value
      for BMD when including age and body weight in the equation. In summary, our data
      indicate that serum ucOC is an independent determinant of BMD of the hip in
      elderly women. The mechanism by which serum ucOC is related to bone mass is
      unclear and should be addressed in further studies. However, our data suggest
      that ucOC level may be an interesting marker in the investigation of bone status
      in the elderly.

PMID- 7817804
TI  - Calcitonin inhibits testosterone and luteinizing hormone secretion through a
      mechanism involving an increase in cAMP production in rats.
AB  - Effects of calcitonin peptides, including human calcitonin (hCT), salmon
      calcitonin (sCT), and calcitonin gene-related peptide (CGRP), on the secretion of
      testosterone and luteinizing hormone (LH) in male rats were studied. Male rats
      were injected intravenously with human chorionic gonadotropin (hCG), calcitonin
      peptides, or hCG plus calcitonin peptides. Blood samples were collected at
      several intervals following hormone challenge. In an in vitro experiment, testis
      blocks were incubated with hCG (0, 0.05, 0.5, or 5 IU/ml) or hCG (0.5 IU/ml) plus
      calcitonin peptides (0-10(-9) or 10(-6) M) at 34 degrees C for 30 minutes. Both
      medium and plasma samples were extracted by ether and analyzed for testosterone
      by radioimmunoassay (RIA). The concentration of calcium in each plasma sample was
      measured by an automatic calcium analyzer. The anterior pituitary gland (AP) was
      incubated with or without calcitonin peptides (0-10 nM) at 37 degrees C for 30
      minutes. They were then incubated with gonadotropin releasing hormone (GnRH, 10
      nM) for a further 30 minutes. The concentration of LH in AP medium was measured
      by RIA. The accumulation of cyclic adenosine monophosphate (cAMP) and cyclic
      guanosine monophosphate (cGMP) in both testicular tissues and APs were measured
      by RIA. A single intravenous injection of calcitonin peptides decreased the basal
      and hCG-stimulated levels of plasma testosterone gradually from 60 to 180 or 360
      minutes after challenge. The plasma calcium was not altered by the injection of
      calcitonin peptides and/or hCG. Administration of calcitonin peptides in vitro
      resulted in a dose-dependent inhibition of both basal and hCG-stimulated release
      of testosterone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7817806
TI  - Bone sialoprotein is localized to the root surface during cementogenesis.
AB  - Bone sialoprotein (BSP), an RGD-containing protein with cell attachment
      properties, is believed to play a regulatory role in the biomineralization of
      various connective tissues. To determine its possible role in tooth root
      formation, murine dentoalveolar tissues at sequential phases of development were
      analyzed immunohistochemically for the presence of BSP. BSP was localized to
      alveolar bone and cementum at time points associated with initial mineralization
      of these tissues. In addition, northern blot analyses of dental follicle tissue
      at day 27 of tooth development indicated that BSP mRNA is expressed by dental
      follicle cells at a time point coincident with the initiation of cementogenesis
      on the peripheral tooth root surface. Collectively, these findings indicate that
      BSP may play an important role in the formation and mineralization of cementum.

PMID- 7817807
TI  - Bone mass improves in alcoholics after 2 years of abstinence.
AB  - To evaluate the effect of abstinence on bone mass and bone mineral metabolism in
      chronic alcoholics, a 2 year longitudinal follow-up study was carried out in a
      group of 30 chronic alcoholic males who started a rehabilitation program. Lumbar
      and femoral bone mineral density (BMD) and serum levels of osteocalcin and 25
      hydroxyvitamin D were measured at entry and after 1 and 2 years in all patients.
      Circulating cortisol and parathyroid hormone were measured in 14 and 6 patients,
      respectively, at entry and every year. Testosterone was measured in 18 patients
      at entry and after 1 year. At entry, lumbar BMD was significantly lower in
      alcoholics (1.06 +/- 0.03 g/cm2) than in age-matched healthy men (1.22 +/- 0.03
      g/cm2; p < 0.001). Circulating osteocalcin and vitamin D levels were also
      significantly lower in alcoholics than in controls. Lumbar and femoral neck BMD
      increased in alcoholics after 2 years of abstinence (lumbar BMD, mean +/- SEM,
      1.06 +/- 0.03 to 1.10 +/- 0.04 g/cm2, p < 0.05; femoral BMD, 0.82 +/- 0.02 to
      0.84 +/- 0.02 g/cm2; p < 0.02). Moreover, lumbar BMD increased in alcoholics (2.9
      +/- 1.4%) and decreased in controls (-1.1 +/- 0.2%; p < 0.02). Femoral BMD also
      increased in alcoholics (2.8 +/- 1.0%) but the expected mean decrease of -0.92%
      was found in healthy age-matched males. Baseline low osteocalcin levels (5.1 +/-
      0.6 ng/ml) increased after 1 year (8.6 +/- 0.5 ng/ml, p < 0.001) and 2 years of
      abstinence (9.5 +/- 0.7 ng/ml, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7817808
TI  - Effects of free mobilization and low- to high-intensity treadmill running on the
      immobilization-induced bone loss in rats.
AB  - After an immobilization period of 3 weeks, the effects of free remobilization (8
      weeks) as well as low- and high-intensity treadmill running on the bone mineral
      content (BMC) and density (BMD) of the hindlimbs of Sprague-Dawley rats (n = 70)
      were studied using a dual-energy x-ray absorptiometric scanner. In the low
      intensity running program, the rats were allowed to move freely in the cage for 1
      week, after which they started to run on a treadmill twice a day for 7 weeks. The
      speed of the treadmill was 20 cm/s, with an uphill inclination of 10 degrees. The
      running time was gradually increased from 20 minutes per session to 45 minutes
      per session. In the high-intensity group, the program was similar, with the
      exception that the speed of the treadmill was 30 cm/s, with an uphill inclination
      of 30 degrees. Immobilization for 3 weeks produced a significant BMC and BMD loss
      in the immobilized left femur and tibia (mean loss 9.6%, p < 0.001) but did not
      affect the right free limbs. Both low- and high-intensity running restored
      mineral content in the immobilized limb; however, an average 5% difference (p <
      0.05) in mineral content of the right and left limb bones persisted. In the
      running groups, the values for the immobilized left limbs were at the same level
      or exceeded (range 3.8-11.6%, p < 0.05-0.01) and those of the free right limbs
      exclusively exceeded (range 5.3-15.9%, p < 0.05-0.01) the corresponding values of
      the age-matched control rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7817809
TI  - Determinants of endogenous fecal calcium in healthy women.
AB  - Endogenous fecal calcium (EFC) excretion was measured in 518 studies in 191
      normal perimenopausal women, most studied two to three times over a 15 year
      period. EFC averaged 102 +/- 25 mg/day. Absorption fraction was simultaneously
      determined by both double-isotope and balance methods. EFC was found to vary
      inversely with absorption fraction, and the observed relationship was used to
      calculate the total amount of calcium (TIC) entering the gut from endogenous
      sources. TIC averaged 140 +/- 34 mg/day and was found to be correlated with a
      number of intake and body size variables. Phosphorus intake was the most strongly
      correlated of all the variables (r = 0.404; P < 0.0001), each increment of 0.1 g
      phosphorus intake being associated with an increase in TIC of 6 mg. Lean body
      mass was the best correlated of the body size variables, with TIC rising by 1.6
      mg/day for every kg lean mass. There were also small but significant correlations
      with protein and energy intakes, the latter suggesting that some of the variation
      of TIC is related to the amount of food consumed. Caffeine, previously reported
      as elevating TIC, did not exhibit a significant relationship in this study.

PMID- 7817810
TI  - Comparison of two parathyroid hormone assays for the rat: the new
      immunoradiometric and the older competitive binding assay.
AB  - A competitive binding assay for parathyroid hormone (PTH INS) has been used since
      1986 to measure PTH in rats. During the past year an immunoradiometric assay for
      the measurement of PTH (PTH IRMA) in the rat was developed. The purpose of the
      present study was to compare results obtained with the PTH INS and IRMA and to
      provide a framework for comparison for investigators who have used the PTH INS in
      previous studies. A total of 99 rats were studied; 27 rats had normal renal
      function, and 72 rats had surgically induced renal failure. In the azotemic rats,
      the magnitude of hyperparathyroidism was varied by changing the calcium and
      phosphorus composition of the diet. The correlation between the two PTH assays in
      the 99 rats was r = 0.98, p < 0.001. For the 27 rats with normal renal function,
      the correlation even within the narrow range of normal PTH values was
      significant, r = 0.71, p < 0.001. In the 72 azotemic rats, in which the highest
      INS PTH value was approximately 17 times normal, the correlation between the two
      PTH assays was r = 0.98, p < 0.001. The PTH IRMA provides distinct advantages,
      such as extended standard range, shortened incubation time, increased
      sensitivity, and technical simplicity, but our results indicate that the PTH INS
      provided an accurate measurement of PTH. Furthermore, our results should provide
      investigators who have used the PTH INS in previous studies with a framework for
      comparison with studies in which the PTH IRMA was used.

PMID- 7817811
TI  - Effects of transforming growth factor beta 1 on the regulation of osteocalcin
      synthesis in human MG-63 osteosarcoma cells.
AB  - Treatment of human MG-63 osteosarcoma cells with human recombinant transforming
      growth factor beta 1 (TGF-beta 1) was found to inhibit cell proliferation. In
      addition, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]-induced osteocalcin synthesis
      was greatly influenced by TGF-beta 1. Dose- and time-dependent inhibition was
      seen both in medium osteocalcin and the corresponding mRNA concentrations.
      Furthermore, TGF-beta 1 decreased osteocalcin synthesis modulated negatively by
      dexamethasone or positively by retinoic acid. The stability of osteocalcin mRNA
      was not decreased by the TGF-beta 1 treatment, but in vitro transcription assays
      demonstrated diminished osteocalcin gene transcription caused by the TGF-beta 1
      treatment. Binding of vitamin D receptor (VDR) to an oligonucleotide probe
      containing the osteocalcin vitamin D response element (VDRE) was not influenced
      by TGF-beta 1, however. Incubation of the cells with the serine/threonine kinase
      inhibitor H-7 did not block the ability of TGF-beta 1 to decrease osteocalcin
      synthesis but caused a further inhibition. Also, the 1,25(OH)2D3-induced
      osteocalcin synthesis was decreased by H-7 treatment, suggesting that
      phosphorylation as such is involved in the transcriptional activation mechanism
      of VDR. These results demonstrate that TGF-beta 1 is a strong inhibitor of the
      synthesis of osteocalcin, a calcium binding protein participating in bone
      mineralization, by counteracting the stimulatory effects of other hormones on its
      synthesis. We further suggest that TGF-beta 1 affects the synthesis of
      osteocalcin at the level of transcription through mechanism(s) different from the
      serine/threonine kinase pathway.

PMID- 7817812
TI  - Direct, enzyme-linked immunoassay for urinary deoxypyridinoline as a specific
      marker for measuring bone resorption.
AB  - Several studies in recent years have shown that the pyridinium crosslinks of
      collagen provide good urinary markers of collagen degradation, primarily
      reflecting bone resorption. Most studies, however, were based on time-consuming
      HPLC assays of the crosslinks. We now describe the development of an immunoassay
      (ELISA) based on a monoclonal antibody for free deoxypyridinoline (Dpd) and its
      use in healthy individuals and patients with bone-related disorders to measure
      the urinary excretion of Dpd as an improved assessment of bone resorption rate.
      The Dpd antibody exhibited less than 1% cross-reaction with free pyridinoline and
      was shown to react only with free Dpd in urine, having no significant interaction
      with peptide forms of the crosslinks. The intra- and interassay variations were
      less than 10 and 15%, respectively. A total of 402 urine samples from patients
      and healthy volunteers were analyzed by both the immunoassay and HPLC. The ELISA
      results were highly correlated with those for total Dpd measured by HPLC over the
      full range of sample groups (r = 0.95). In normal adults, the excretion of Dpd
      (mean +/- SD) was 4.7 +/- 1.6 nmol/mmol creatinine, with about fivefold higher
      excretion rates in children. For 31 osteoporotic patients, the ELISA Dpd values
      (median 6.7; range 3.0-13.5 nmol/mmol Cr) were significantly higher (p < 0.0001)
      than the corresponding values for age- and sex-matched controls (median 4.0;
      range 1.8-7.4). The difference between the groups was similar for total Dpd by
      HPLC (osteoporotic: mean 12.8, range 4.8-30.7; controls: 6.6, range 3.0-18.1; p <
      0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7817813
TI  - Small-angle x-ray scattering study of dispersed crystals from bone and tendon.
AB  - A small-angle x-ray scattering study of dispersed crystals from rat bone and
      mineralized turkey tendon shows that the particles in both preparations have the
      same scattering behavior. The data are very similar to those reported by Fratzl
      et al. for intact turkey tendon and are consistent with the crystals being plate
      shaped. These observations have important implications for understanding both the
      structure and mineralization processes of these tissues.

PMID- 7817814
TI  - Brittle bones in spontaneously diabetic female rats cannot be predicted by bone
      mineral measurements: studies in diabetic and ovariectomized rats.
AB  - Spontaneously diabetic BB rats were sham operated (SO) or ovariectomized (OVX)
      within days after onset and studied after 4, 8, and 12 weeks. Analyses included
      histomorphometry of proximal tibial metaphyses, biochemical analyses of humeri,
      DXA analyses, and biomechanical testing of femora. In SO diabetic rats, no
      osteoblasts, osteoid tissue, or osteoclasts were present on the trabecular bone
      surface, but trabecular bone volume (TBV) remained normal compared with control
      BB rats. The concentration of IGF-I per dry weight of humerus was decreased after
      12 weeks of diabetes, whereas the concentrations of calcium and osteocalcin did
      not change. DXA analysis showed normal bone mineral density (BMD) at both
      diaphyseal and metaphyseal femoral areas. On biomechanical testing, angular
      deformation, energy absorption, and torsional strength of the femora were
      decreased after 8-12 weeks of diabetes, but stiffness was normal. Ovariectomy in
      diabetic rats caused a decrease in femoral BMD especially at the metaphysis, and
      there was a trend toward decreased TBV in the tibial metaphysis; TBV loss was
      less marked than in control OVX rats, however. The increase in BMD at the femoral
      diaphysis, measured after 12 weeks of OVX in control rats, was absent in diabetic
      rats. Multiple-regression analysis indicated that the presence of diabetes but
      not ovariectomy, weight, and mineral content correlated with decreased energy
      absorption, angular deformation, and strength of the femora. The data infer that
      the (near) absence of unmineralized bone matrix in severely diabetic rats alters
      bone microarchitecture and ultimately results in brittle bones, which is not
      predicted by BMC or BMD measurements.

PMID- 7817815
TI  - Cultural determinants of skeletal health: the need to consider both race and
      ethnicity in bone research.

PMID- 7817816
TI  - Sex differences in bone mineral density in 1653 men and women in the sixth
      through tenth decades of life: the Rancho Bernardo Study.
AB  - This cross-sectional population-based study examined the effect of age and sex on
      bone mineral density (BMD) in the elderly. BMD was measured at the spine and hip
      using dual-energy x-ray absorptiometry and at midshaft and ultradistal radius
      using single-photon absorptiometry in 672 men and 981 women aged 50-98 years. In
      both sexes, mean BMD levels decreased significantly with age at all sites except
      the male spine. In linear regression models, the slope of loss was significantly
      greater in women than in men at all sites except the ultradistal radius. The
      slope was steeper at most sites in women aged 50-59 years than in older women, 60
      98 years. In both age groups, mean age-adjusted BMD levels were lower at all
      sites in women who were past or never users of replacement estrogen than in women
      who were current estrogen users. Current estrogen users generally had lower
      slopes of loss with age than never or past estrogen users; however, few of these
      differences were statistically significant. We conclude that BMD levels decrease
      in old age in both sexes. Continued bone loss in old age raises the possibility
      that intervention to retard further loss may still be warranted in the elderly.

PMID- 7817817
TI  - Lifestyle factors and bone density in the elderly: implications for osteoporosis
      prevention.
AB  - Epidemiologic evidence suggests that lifestyle factors, such as exercise, calcium
      intake, and tobacco consumption, have effects on bone density. However, the
      influence of these factors in the elderly has not been well documented. To
      examine the effects of lifestyle factors in the elderly, we measured bone density
      (BMD) at the lumbar spine and proximal femur in 709 elderly men and 1080 women
      participating in the Dubbo Osteoporosis Epidemiology study (DOES), a community
      based, longitudinal, epidemiologic study of osteoporosis in men and women over
      the age of 60. BMD was significantly higher in men than in women (20% at all
      sites). There was an age-related decline in BMD at the femoral neck in both sexes
      and at the lumbar spine in women. Between the ages of 60 and 80, the decrease in
      BMD at the femoral neck among women was 18.9%, which is almost twice the decrease
      in BMD among men (10.1%). Tobacco consumption was associated with a reduction in
      BMD at both sites in both sexes (5-8%), and this effect was independent of
      calcium intake or body weight. Exsmokers had BMD intermediate between that of
      current smokers and never smokers, suggesting the influence of tobacco was
      partially reversible. Quadriceps strength predicted bone density at the proximal
      femur in elderly men but not in women. Analyzing BMD (adjusted for age and
      weight) in tertiles of muscle strength and calcium intake revealed an interaction
      between calcium intake and muscle strength on bone density; BMD at the femoral
      neck among those with higher quadriceps strength and calcium intake was
      approximately 5% higher (P < 0.05) than in those with low quadriceps strength and
      calcium intake in both men and women.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7817818
TI  - Regulation of collagen type I and biglycan mRNA levels by hormones and growth
      factors in normal and immortalized osteoblastic cell lines.
AB  - Growth factors, such as transforming growth factor beta (TGF-beta) and insulin
      like growth factors (IGF) I and II, have been shown to exert anabolic effects on
      bone cells in vitro. Hormones, such as PTH and probably insulin and growth
      hormone, were recently shown to stimulate bone formation in vivo as well. The aim
      of the present study was to assess by northern blots, which were quantitated by
      densitometry, the effects of these anabolic growth factors and hormones in two
      osteogenic cell populations: CRP 10/30 cells, a clonal cell population derived
      from primary rat calvarial cells, and IRC 10/30-myc cells, which were established
      from CRP 10/30 by immortalization. Transcripts for alpha 1(I) collagen, biglycan,
      osteonectin, osteopontin, and osteocalcin were detected in both cell populations,
      which is consistent with the phenotype expressed by mature osteoblasts. There
      were no difference in the basal expression of bone matrix mRNAs between the two
      cell populations. PTH increased alpha 1(I) collagen mRNA levels in both
      osteoblastic cells but had no effect on the biglycan transcripts. Neither insulin
      nor growth hormone affected mRNA levels of either matrix protein after 24 h
      exposure. All three growth factors, TGF-beta, IGF-I, and IGF-II, increased alpha
      1(I) collagen transcripts in a time- and dose-dependent manner in both cell
      populations. Biglycan mRNA levels were enhanced in both osteoblastic lines only
      by IGF-I and IGF-II, but not TGF-beta.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7817819
TI  - Normal osteoclastic and osteoblastic responses to exogenous growth hormone in
      patients with postmenopausal spinal osteoporosis.
AB  - The cause of bone loss in patients with osteoporosis is not known, but both
      increased bone resorption and decreased bone formation have been reported.
      Theoretically, these effects may result from either increased activity of
      osteoclasts or decreased activity of osteoblasts, or both. In vivo, growth
      hormone (GH) administration leads to activation of osteoclasts and osteoblasts as
      evidenced by increased biochemical markers of bone resorption and bone formation.
      To test for disturbances in responsiveness of bone cells to exogenous hormonal
      stimuli in osteoporosis, we compared 15 patients with postmenopausal osteoporosis
      with 15 healthy age-matched postmenopausal women before and during a 3 day
      stimulation test with GH (0.2 IU/kg/day). Serum insulin-like growth factor I
      increased in both groups (p < 0.001). GH treatment increased biochemical markers
      of bone resorption (serum carboxyl-terminal telopeptide of type I collagen [ICTP]
      [p < 0.001] and, to a lesser extent, 24 h urinary hydroxyproline/creatinine) in
      the two groups. Similarly, biochemical markers for bone formation increased in
      both groups [osteocalcin (p < 0.01) and procollagen type I C-terminal propeptide,
      PICP (p < 0.001)]. GH treatment reduced alkaline phosphatase (ALP, p < 0.05) and
      its bone-specific isoenzyme (bone ALP, p < 0.01) in both groups. The maximal
      response, the area under the curve (AUC) of response curves for IGF-I, bone
      resorption markers, and bone formation markers were not different between groups.
      Our data do not support the hypothesis that osteoporotic patients display major
      disturbances in responsiveness to GH.

PMID- 7817820
TI  - Serum parathormone profile during surgical treatment of hyperfunctioning
      parathyroid adenoma: a multicompartmental model.
AB  - Patterns of intact parathyroid hormone (iPTH) elimination and subsequent recovery
      of parathyroid function were studied in seven patients undergoing surgical
      removal of solitary hyperfunctioning parathyroid adenoma. Using a sensitive two
      site immunoradiometric assay, iPTH levels were measured pre, peri-, and
      postoperatively. Blood samples were taken at very early and at late stages,
      including 3, 6, 9, and 15 minutes and 48, 72, and 96 h after adenomectomy. A
      biexponential formula was calculated to fit the decreasing values of iPTH in all
      patients. The PTH half-life in the early phase was 1.4 +/- 1.1 minutes (95%
      confidence limits). The PTH half-life in the second phase was 64.45 +/- 32.19
      minutes (95% confidence limits). A third phase is represented by a slow, linear
      increase in plasma iPTH values as a result of the recovery of healthy suppressed
      parathyroid glands. The extrapolation to baseline of the later phase shows that
      the recovery of normal parathyroid function begins as soon as 240 minutes after
      adenomectomy and is independent of the decrease in PTH of adenomatous origin. All
      individual results were consistent with this model. Five patients had iPTH values
      below 5 pg/ml, one had 15 pg/ml, and the last had 27 pg/ml 5 h after parathyroid
      adenomectomy. The recovery of the hormonal activity of the remaining glands
      occurred rapidly. By the postoperative hour 24 the mean serum iPTH concentration
      was 12.28 +/- 8.07 pg/ml. The intraoperative serum iPTH concentration offers a
      model to assess both recovery of hormonal secretion from functionally suppressed
      parathyroid glands and disappearance of parathyroid hormone.

PMID- 7817821
TI  - Comparison of dosage-dependent effects of beta-aminopropionitrile, sodium
      fluoride, and hydrocortisone on selected physical properties of cortical bone.
AB  - BAPN, sodium fluoride, and hydrocortisone are reported to induce altered
      mineralization states. Three separate sets of experiments, one set for each
      agent, were performed using male New Zealand white rabbits. In each experiment
      the rabbits were segregated into groups, each fed a specified weight-determined
      dose for 13 weeks and then sacrificed. Compact bone from the left femur and tibia
      were tested for density, composition, sonic velocity, longitudinal elastic
      modulus, equatorial diffraction spacing of mineralized collagen, diaphyseal cross
      sectional area, and relative load stress. beta-Aminopropionitrile (BAPN) induced
      monotonic degradation of all properties at all dose levels, corresponding to the
      decreasing density with dosage level. The elastic moduli show a decrease; the
      equatorial diffraction spacing of the collagen increases. The cross-sectioned
      diaphysis resembled woven bone. The variability in properties increased with
      dosage. The total cross-sectional area for a given weight increased, implying
      that the decreased elastic properties were compensated for by a larger area to
      support the weight. There was a slight increase in average density and other
      properties for fluoride-treated rabbits, peaking at 20 mg/kg BW/day. For higher
      dosages the properties are degraded and the values were much lower at high
      fluoride dosages than for BAPN. There was no peak for the equatorial diffraction
      spacing, which increased with dosage. It is inferred that the fluorosed apatite
      is denser than normal apatitic mineral and therefore has a smaller specific
      volume. A greater weight fraction of fluorosed mineral has a smaller volume
      fraction than the equivalent normal apatitic mineral. The bone sections look more
      normal, except for the porosis. The total cross-sectional area decreases when the
      bone density increases and then increases as the density falls, again implying
      that the area required to support body weight depends on the magnitude of the
      elastic moduli. There was a small change in some of the properties of the bones
      of the hydrocortisone-treated rabbits, but the effects on others were
      undetectable within the uncertainty of the procedures. There was no change in the
      cross-sectional areas of the diaphyses.

PMID- 7817822
TI  - Force attenuation properties of various trochanteric padding materials under
      typical falling conditions of the elderly.
AB  - The purpose of this study was to determine and compare the force attenuation
      properties of various external trochanteric padding materials under in vitro
      conditions simulating characteristic falling of the elderly. The selected
      materials had to be practically suitable for external hip padding so that the
      main criteria for the materials were good energy absorbing capacity, good
      durability, low weight, good recovery after compression, easy availability, and
      reasonable price. Eight materials met these requirements. The first six were
      flexible cross-linked polyethylene foams with densities from 30 to 200 kg/m3. The
      seventh material was Plastazote polyethylene foam, and the eight foam was made of
      ethylene-vinyl acetate (EVA) copolymer. With a pendulum effective mass of 39 kg,
      impact velocity of 3.0 m/s, and impact force of 8.2 kN, the force attenuation
      provided by the 20 mm thick hip-padding materials was quite small, ranging from
      22 to 38%. With all these materials the peak femoral force remained above 5 kN,
      more than two times above the femoral fracture threshold (2 kN). In the second
      set of experiments, the impact force was gradually reduced until the tested
      materials lowered the impact force below the fracture threshold. With the most
      efficient material this critical falling velocity was found to be 1.6 m/s. To go
      below the fracture threshold with the realistic impact velocity of 3.0 m/s, the
      padding materials had to be 100-140 mm thick.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7817823
TI  - Displacement and translocation of osteoblast-like cells by osteoclasts.
AB  - Rabbit osteoclasts and rabbit osteoblast-like stroma cells (OB cells) were placed
      onto plastic surfaces and the migration patterns of individual osteoclasts and
      osteoclast-OB interactions were analyzed with time-lapse recording. To induce
      directed migration, the cultures were exposed to an electrical field of 0.01 or
      0.1 V/mm. At 0.1 V/mm, osteoclasts moved directly toward the anode in some cases,
      clearing OB cells from their path of migration. In other cases, osteoclasts
      migrated toward the anode for part of the time but then changed direction and
      moved toward groups of OB cells. Observations were made on osteoclasts
      interacting with single OB cells or small colonies and on osteoclasts interacting
      with OB monolayers, at both field strengths; the results were independent of
      field strength. There were several characteristic behaviors. With single OB cells
      and small OB colonies, retraction of OB cells upon contact with the osteoclast
      was the predominant mechanism whereby these cells begin to move out of the path
      of the osteoclast. A pronounced ruffling or blebbing of the OB cell membrane
      often followed retraction. When osteoclasts displaced OB cells that were part of
      a monolayer, extension of an osteoclast lamellipodium underneath the edge of the
      OB cell layer generally preceded partial retraction of the OB cells involved. It
      sometimes appeared as if the detached or partially detached OB cells were
      "pushed" by the osteoclast, which in some cases resulted in OB cells being moved
      hundreds of microns in a period of a few hours, at rates comparable to the normal
      speed for osteoclast migration (congruent to 100 microns/h), much faster than the
      normal speed for OB cells (congruent to 10 microns/h).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7817824
TI  - Single-cell analysis of cyclic AMP response to parathyroid hormone in
      osteoblastic cells.
AB  - We previously demonstrated that the [Ca2+]i response to PTH is heterogeneous in
      single UMR-106-01 osteogenic sarcoma cells. To verify whether response
      heterogeneity is a universal feature of PTH signal transduction, cAMP production
      was monitored in monolayer cultures of UMR-106-01 cells and human trabecular bone
      osteoblasts (HOB) using the cAMP-sensitive fluorescent indicator FlCRhR. FlCRhR
      was microinjected into single cells, and the 500-530/> 560 nm fluorescence ratio
      was monitored by confocal laserscanning video imaging as a measure of cAMP
      concentration ([cAMP]). Virtually all UMR-106-01 cells exposed to bovine PTH(1
      34) (10(-7) M) exhibited an increase in intracellular [cAMP], with an average
      fluorescence ratio change of 145 +/- 17% of baseline (n = 15), corresponding to
      nearly maximal dissociation of protein kinase A. In the continued presence of the
      hormone (10(-7) M), [cAMP] remained elevated for at least 30 minutes. This effect
      was accompanied by a slow translocation of the fluorescein-labeled catalytic
      subunit of protein kinase A from the cytoplasm to the nucleus. In contrast, PTH(1
      34) caused no detectable increase in [cAMP] in HOB cells, although PGE2 (3 x 10(
      6) M) stimulation was able to increase the FlCRhR ratio (154 +/- 27%, n = 10).
      The truncated fragment PTH(2-34) was only 67% as potent at PTH(1-34), but
      deletion of the first two amino acids at the N terminus abolished the hormone's
      ability to stimulate cAMP production in UMR-106-01 cells. Brief exposure to 10(
      7) M of either PTH(3-34) or PTH(7-34) did not affect the amplitude of the
      fluorescence ratio change induced by equimolar doses of PTH(1-34). Thus, in
      osteoblast-like cells stimulated with PTH, the [cAMP] response is much more
      homogeneous from cell to cell than the [Ca2+]i response.

PMID- 7817825
TI  - Cancellous bone turnover in growing rats: time-dependent changes in association
      between calcein label and osteoblasts.
AB  - Calcein was given to growing male rats to label mineralizing bone, and groups of
      animals were sacrificed from 6 h to 12 days later. Fluorochrome-labeled perimeter
      and osteoblast perimeter were determined in a growth-adjusted sampling site in
      the secondary spongiosa of the proximal tibial metaphysis. The best
      correspondence between calcein-labeled perimeter and osteoblast-lined perimeter
      was during the initial 24 h following administration of the label. This
      association decreased progressively thereafter because of (1) cessation of bone
      formation on fluorochrome-labeled surfaces and (2) initiation of new foci of bone
      formation. The time-dependent decline in osteoblast-lined trabeculae with
      adjacent calcein label exceeded the increase in osteoblast perimeter on
      nonfluorochrome-labeled trabeculae, indicating that there was a net decrease in
      osteoblast number. Fluorochrome-labeled perimeter and bone area showed parallel
      decreases with time after labeling, as a result of bone resorption.
      Interestingly, the decrease in cancellous bone was caused exclusively by a
      reduction in trabecular number. There was no change in trabecular thickness. The
      findings suggest that the decreased osteoblast number and progressive bone
      resorption resulted in complete erosion of trabeculae most distal to the growth
      plate. As a result of the nearly equal growth and destruction of trabeculae,
      there was no change in the length of the cancellous metaphysis with time. It is
      concluded that cancellous bone turnover in growing rats represents a maturation
      process that differs fundamentally from bone turnover in adults.

PMID- 7817826
TI  - Dual x-ray absorptiometry forearm software: accuracy and intermachine
      relationship.
AB  - An ash study was performed to analyze the accuracy of forearm measurements at the
      one-third site of three dual x-ray absorptiometry (DXA) systems using 20
      cadavers. A Hologic QDR-2000, a Hologic QDR-1000/W, and a Lunar DPX-L system were
      used. The correlations between ash weight and DXA BMC were excellent for the
      three instruments (r > 0.97, p < 0.001), with accuracy errors < 5.2%. To perform
      a forearm cross-calibration of bone mineral content (BMC) and density (BMD)
      between the scanners, 10 healthy volunteers were additionally scanned at the
      distal one-third radius. The correlations among the DXA machines were excellent
      (r > 0.95); the absolute BMC and BMD values were significantly different between
      the two Hologics and the Lunar machine. The slope and intercept of both the BMC
      and BMD between the two Hologic systems were close to unity. In conclusion, the
      DXA forearm software packages provide accurate methods for assessing bone mineral
      content and density. The conversion of data among different manufacturers should
      be performed by careful cross-calibration measurements.

PMID- 7817827
TI  - Does estimating volumetric bone density of the femoral neck improve the
      prediction of hip fracture? A prospective study. Study of Osteoporotic Fractures
      Research Group.
AB  - Standard projectional bone density of the femoral neck (BMD), defined as bone
      mineral content divided by the projected area of the neck, predicts hip fractures
      but may not accurately estimate the true volumetric bone density of the femoral
      neck. To determine whether an estimate of the volumetric bone density of the
      neck, "bone mineral apparent density" (BMAD), would be a better predictor of hip
      fracture, we analyzed dual x-ray absorptiometry scans obtained prospectively from
      7963 older white women, of whom 83 suffered a hip fracture during follow-up. Both
      BMD and BMAD were stronger predictors than bone mineral content (BMC) of the
      femoral neck. However, BMD and BMAD had very similar predictive values for hip
      fracture: each standard deviation decrease in either BMD or BMAD of the femoral
      neck increased the age-adjusted risk of hip fracture 2.6- to 2.7-fold. We
      conclude that BMD and BMAD of the femoral neck have a similarly strong predictive
      value for hip fracture.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7817828
TI  - Urinary hydroxypyridinium crosslinks of collagen in population-based screening
      for overt vertebral osteoporosis: results of a pilot study.
AB  - The urinary pyridinium crosslinks pyridinoline (PYD) and deoxypyridinoline (DPD)
      have been shown to provide valid indices of bone resorption. At present, both
      crosslink components are determined by reversed-phase HPLC, a time-consuming
      method precluding the use of these markers for routine purposes. Therefore,
      efforts have been made to develop simple immunoassays for the rapid measurement
      of urinary crosslinks, and their application to large-scale osteoporosis
      screening has been proposed. To evaluate the applicability and diagnostic
      validity of pyridinium crosslink measurements for screening purposes, urinary
      concentrations of total and free PYD and DPD were determined by HPLC and
      immunoassay technique (ELISA) in a sample of 269 individuals (male to female
      ratio = 130:139; age 50-81 years) recruited at random within a population survey
      of vertebral osteoporosis. On a molar basis, ELISA measures of crosslink-related
      epitopes were highly correlated with both total and free PYD and DPD as
      determined by HPLC (r > 0.82, p < 0.001). Age-specific means for creatinine
      corrected total and free pyridinium crosslinks were significantly higher in
      females than in males (p < 0.001). In both sexes, neither age nor anthropometric
      variables (weight, height, and body mass index) showed a linear effect on the
      urinary crosslink/creatinine ratio. On average, 50% of the total amount of
      urinary crosslinks were present in free form. For both PYD and DPD, this
      proportion was significantly higher in women than in men (p < 0.05), but no
      change was observed with age or anthropometric measures. The excretion of
      pyridinium crosslinks was higher in osteoporotic (n = 18) than in nonosteoporotic
      individuals (n = 208) from the same population.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7817829
TI  - Structure-activity studies of the s-echistatin inhibition of bone resorption.
AB  - Synthetic Arg-Gly-Asp (RGD)-containing peptides were examined in bone resorption
      or attachment and detachment assays with isolated mammalian osteoclasts in an
      effort to elucidate the mechanistic and structural basis for the inhibition of
      bone resorption by s-echistatin. Bone resorption was the process most sensitive
      to inhibition by s-echistatin, with IC50 = 0.3 nM; inhibition of attachment to
      bone or detachment (lamellipodial retraction) was 30- to 70-fold less sensitive,
      with IC50 = 10 or 20 nM, respectively. Single amino acid substitutions within the
      49-residue sequence of s-echistatin showed that although the efficacy of s
      echistatin is dependent on the Arg24-Gly25-Asp26 sequence, additional residues,
      including Asp27, Met28, and Cys39, are also critical for potent inhibition of the
      resorbing activity of isolated rat osteoclasts. Because of the identification of
      the av beta 3 as the primary integrin on rat osteoclasts interacting the RGD
      peptides (Helfrich et al.), we examined the possibility of modeling bone
      resorption with other beta 3-mediated processes. Specifically, av beta 3
      endothelial cell (human or rat) attachment to vitronectin and aIIb beta 3
      platelet aggregation were compared with bone resorption for sensitivity to s
      echistatin analogs, linear RGD peptides, and cyclic RGD peptides. Essentially no
      similarity in sensitivity to RGD peptides were observed between bone resorption,
      platelet aggregation, or endothelial cell attachment. Because rat osteoclasts and
      human giant cell tumors (osteoclastomas) shared similar sensitivity to s
      echistatin and rat and human endothelial cells showed a similar sensitivity
      profile to RGD peptides, the dissimilarity of bone resorption to other beta 3
      mediated processes cannot be explained in terms of species differences.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7817830
TI  - Bone mineral density of total body, spine, and femoral neck in children and young
      adults: a cross-sectional and longitudinal study.
AB  - Bone mineral density (BMD) of total body (TBMD), lumbar spine (L2-4), and femoral
      neck was measured in 266 normal subjects (136 males) aged 4-27 years (mean 13
      years) using dual-energy x-ray absorptiometry (DXA). BMD of all sites increased
      significantly with age until 17.5 years in males and 15.8 years in females,
      except for femoral neck BMD in females, which peaked at age 14.1 years. Males had
      higher peak TBMD, which was attributed to greater weight and lean tissue mass. In
      contrast, despite a later timing, peak L2-4 BMD in males was not different from
      that in females. Before peak BMD, weight was the best predictor of TBMD and L2-4
      BMD in both sexes (r2 ranged from 0.77 to 0.88), whereas femoral neck BMD was
      predicted equally by height and weight. Longitudinal information collected from
      53 (25 boys) of these children, aged 4-16.9 years, showed that the average
      annualized gain in TBMD was 0.047 g/cm2 for boys and 0.039 g/cm2 for girls. No
      significant difference in the association between age and BMD (slopes) was found
      between cross-sectional and longitudinal data for either sex. We conclude that
      the timing for peak BMD was consistent for total body, lumbar spine, and femoral
      neck for each sex. The earlier peak BMD in females is most likely related to
      earlier puberty. The cross-sectional normative data of this study are useful in
      serving as a standard for serial assessment in health and disease states.

PMID- 7817831
TI  - Improved method for analysis of whole bone torsion tests.
AB  - Structural tests, such as whole bone torsion tests, have become widely accepted
      methods for assessing average bone material properties. To simplify
      interpretation of these tests, the nonuniform bone geometry is often analyzed as
      a tube with a constant cross section (prismatic) and the areal properties of the
      smallest bone section. This approach may not adequately represent the true
      torsional behavior of the cross section and does not account for any lengthwise
      variations in bone geometry. The errors introduced by these approximations are
      particularly significant when comparing bones of different sizes and geometries.
      In this paper, we examine the effects of approximating the cross-sectional
      torsional behavior and of neglecting lengthwise variations in bone geometry. We
      then present a simple, standardized procedure utilizing a FORTRAN computer
      program for accurate determination of material properties. We examine first
      simple idealized bone geometries and then a complex three-dimensional model of
      the femur from a 26-day-old male Sprague-Dawley rat. For these models, the
      conventional methods for interpreting torsion tests introduce errors of up to 42%
      in the shear modulus and up to 48% in the maximum shear stress; a straightforward
      extension of these methods reduces the errors to within 3%.

PMID- 7817832
TI  - Correlates of bone mineral density in the postmenopausal estrogen/progestin
      interventions trial.
AB  - We assessed the cross-sectional relationship of age, menopausal years, body mass,
      previous estrogen use, and ethnic background to bone mineral status in a sample
      of 875 healthy postmenopausal women at the time they were recruited from the
      community to participate in a multicenter clinical trial. The women were 1-10
      years postmenopause, 45-64 years of age, and had not received estrogen
      replacement therapy within 3 months of enrollment. Of the participants, 89% were
      white, 69% had a spontaneous menopause, and 53% had a history of previous
      estrogen replacement therapy. Bone mineral density (BMD) of the lumbar spine (L2
      4) and proximal femur was measured by dual-energy x-ray absorptiometry. Results
      were consistent with a significant negative linear regression of BMD on age or
      years from menopause. Body mass index (BMI) correlated significantly with BMD at
      all sites (L 2-4 r = 0.28; femoral neck r = 0.34, p < 0.0001). BMD adjusted for
      age and BMI were higher at both sites in women who had taken estrogen versus
      those who had not (L2-4 0.976 +/- 0.009 versus 0.932 +/- 0.01; femoral neck 0.740
      +/- 0.006 versus 0.708 +/- 0.008, p < 0.05). Adjusted BMD also increased with
      duration of ERT. Parity was negatively associated with L2-4 BMD (p = 0.03) but
      did not correlate significantly with BMD at the femoral neck. Black women had the
      highest L2-4 BMD, and Hispanic women had the highest femoral neck BMD, even when
      results were adjusted for age and BMI. When data were corrected for differences
      in bone size, these interethnic differences were no longer significant. We
      conclude that increased body mass is positively correlated with BMD, and this may
      confer a degree of skeletal protection to heavier postmenopausal women. Exposure
      for 5 years to exogenous estrogen is associated with significantly increased age-
      and BMI-adjusted BMD.

PMID- 7817833
TI  - Regulation of protein kinase C by transforming growth factor beta 1 in rat
      costochondral chondrocyte cultures.
AB  - Transforming growth factor beta (TGF-beta) regulates the proliferation and
      differentiation of chondrocytes; however, the mechanism of TGF-beta signal
      transduction remains unclear. We examined whether the response to TGF-beta is
      mediated by protein kinase C activity in chondrocytes at different stages of
      maturation. The aims were to examine the effect of recombinant human TGF-beta 1
      (rhTGF-beta 1) on protein kinase C in rat costochondral chondrocyte cultures;
      determine the major isoform present; assess the involvement of phospholipase C or
      tyrosine kinases; determine whether genomic or nongenomic pathways are involved;
      and test whether these mechanisms differ as a function of the stage of cell
      maturation. Dose-dependent increases in protein kinase C activity were observed
      in confluent, fourth-passage cultures of rat costochondral growth zone and
      resting zone chondrocytes treated with rhTGF-beta 1. In growth zone cells,
      elevated activity was observed at 12 h and decreased markedly by 24 h. In resting
      zone cells, elevated activity was observed at 9 h, maximum stimulation occurred
      at 12 h, and activity returned to baseline levels after 48 h. Immunoprecipitation
      studies showed protein kinase C alpha is the major isoform present in both
      untreated and treated cells. Neither the phospholipase C inhibitor, U73122, nor
      the tyrosine kinase inhibitor, genistein, significantly reduced the protein
      kinase C response to rhTGF-beta 1. Actinomycin D and cycloheximide, inhibitors of
      transcription and translation, produced dose-dependent inhibition of rhTGF-beta 1
      stimulated protein kinase C activity in both resting zone and growth zone
      chondrocytes. The time course of activation and insensitivity to U73122 suggest
      that phospholipase C-mediated events are not involved in rhTGF-beta 1 stimulation
      of protein kinase C in costochondral chondrocytes. Similarly, because genistein
      had no effect, tyrosine kinases are not implicated. Rather, the reduction in
      protein kinase C activity observed when rhTGF-beta 1 is administered along with
      actinomycin D or cycloheximide indicates that new gene expression and protein
      synthesis are required for the response. These results indicate that the effect
      of rhTGF-beta 1 is mediated by protein kinase C; however, it is very slow and may
      require new protein kinase C production, perhaps via a cytokine cascade.
      Moreover, the classic mechanism of activation of protein kinase C by
      phospholipase C was not found, suggesting a novel mechanism of activation.
      Finally, the effects of rhTGF-beta 1 on protein kinase C are dependent on the
      state of cell maturation with respect to onset and duration of response.

PMID- 7817835
TI  - The effect of lead on dopamine, GABA and histidine spontaneous and KCl-dependent
      releases from rat brain synaptosomes.
AB  - The effect of lead on the release of [14C]GABA, [3H]dopamine and [14C]histidine
      (as a precursor of histamine) was studied in synaptosomes obtained from
      chronically lead-treated rats and in synaptosomes with in vitro lead added. In
      vivo treatment of rats with lead acetate results in a decrease in the K(+)
      depolarization-dependent release of GABA and dopamine and histidine. Lead given
      in vitro itself (independently of depolarizing condition) stimulated the release
      of previously accumulated neurotransmitters in synaptosomes (GABA and dopamine).
      This effect depends on lead acetate concentration. On the other hand lead, in
      different concentrations, did not cause changes in the histidine release. The
      results show that lead can attack the synaptic neurotransmission in two ways: by
      depressing the Ca-KCl-evoked release of GABA, dopamine and histidine and by a
      selective stimulation of a spontaneous release (independent of depolarization
      conditions) of GABA and dopamine but not histidine.

PMID- 7817834
TI  - In situ hybridization to show sequential expression of osteoblast gene markers
      during bone formation in vivo.
AB  - We investigated the sequence of expression of osteoblast gene markers during bone
      formation in vivo by in situ hybridization. Cylindrical lesions were induced in
      the femora of sheep with titanium analytic bone implants that allow removal of
      serial core samples to study bone formation. At 2 weeks (2W), granulation tissue
      made up of spindle-shaped cells had partially replaced the blood clot. Islands of
      osseous tissue, first noted in the periphery of the ingrowing tissue at 3W,
      became the predominant tissue by 6W. The surfaces of newly forming bone at 3W
      were apposed by cuboidal cells, which in some areas were several layers thick. By
      6W, most of the cells lining bone trabeculae had assumed a flattened morphology.
      The temporal and spatial distribution of osteoblast gene markers was examined by
      in situ hybridization with nonradioactive digoxigenin probes for alpha 1(I)
      procollagen, alkaline phosphatase (ALP), osteopontin (OP), and bone Gla protein
      (BGP). The spindle-shaped cells in the granulation tissue expressed mRNA for
      alpha 1(I) procollagen, ALP, and OP but not BGP, suggesting that they may be
      osteoblast precursor cells. alpha 1(I) procollagen mRNA was strongly expressed by
      all cells on the surface of bone, with a peak intensity at 3W and then reducing
      sharply by 6W. Initially, only pockets of cuboidal cells on bone surfaces
      expressed ALP mRNA, with a peak intensity at 5W. Similarly, only a proportion of
      cuboidal cells expressed OP mRNA early in bone formation, but the number of cells
      expressing OP mRNA increased with time. Clumps of cuboidal cells expressed BGP
      mRNA only when bone was present, and the degree of expression increased with the
      amount of bone formed. This model allows the study of temporal and spatial
      sequence of gene expression in cells participating in osteogenesis. The temporal
      sequence is similar to that shown in vitro in other models of mineralization. The
      geographic localization of cells expressing mRNA for alpha 1(I) procollagen, ALP,
      OP, and BGP implies subspecialization of osteoblasts in bone formation.

PMID- 7817836
TI  - Further ultrastructural studies of lesions produced in the optic nerve by tumor
      necrosis factor alpha (TNF-alpha): a comparison with experimental Creutzfeldt
      Jakob disease.
AB  - We report here that intraocular injection of recombinant TNF-alpha produces
      lesions in the optic nerve indistinguishable from those reported for the
      panencephalopathic type of Creutzfeldt-Jakob disease (CJD). The lesions were
      patchy and confined to the injected optic nerve. Axons show variable features of
      degenerations. Numerous vacuoles distended the myelin sheath. Hypertrophic
      astrocytes were numerous and many active macrophages containing digested myelin
      debris and lyre-like paracrystalline bodies. At high power, myelinated axons were
      observed as enveloped by astrocytic processes; formation of labyrinth-like
      network of such processes around damaged axons were observed. In conclusions,
      lesions produced by TNF-alpha mimic those of the panencephalopathic type of CJD,
      in direct support of our previous ultrastructural, immunohistochemical and
      molecular data on TNF-alpha involvement in CJD pathogenesis.

PMID- 7817837
TI  - Effects of staphylococcal alpha-toxin on the ultrastructure of the rat
      hypothalamo-neurohypophyseal system.
AB  - The influence of staphylococcal alpha-toxin on the ultrastructure of hypothalamo
      neurohypophysical system in the brain (nucleus supraopticus, nucleus
      paraventricularis, neurohypophysis) was studied in the rat. In neurohypophysis,
      an area lacking blood-brain barrier, alpha-toxin damaged both neuronal endings
      and capillary vessels. On the other hand in hypothalamus, where blood-brain
      barrier is present structural alterations were much less pronounced. Reactive
      gliosis, accordant with cell damage, was observed in the entire neurosecretory
      system. Putative mechanisms leading to brain damage after systemic administration
      of alpha-toxin, including direct disruption of cell membrane and induction of
      nitric oxide synthesis, are discussed.

PMID- 7817838
TI  - Dopaminergic innervation of the brain in pigeons. The presumed 'prefrontal
      cortex'.
AB  - In the postero-dorso-lateral neostriatum (PDLNS) of the pigeon we found a high
      density of tyrosine hydroxylase and perineuronal nests of fibres labelled with
      anti-dopamine antibody. These data confirm our earlier indirect evidence that
      PDLNS receives a dense dopaminergic innervation and therefore can be compared
      with the mammalian prefrontal cortex.

PMID- 7817839
TI  - Antidromic field potentials recorded from cell groups of S2 spinal cord segment
      with axons in the opposite Th13 dorsolateral funiculus in the cat.
AB  - Location of cell groups within gray matter of S2 spinal cord segment, whose axons
      are running in the opposite Th13 dorsolateral funiculus, were studied by means of
      antidromic field potentials recorded in chloralose anaesthetized cats. The cell
      bodies are forming six separate groups occupying medial laminae II and III,
      medial laminae IV and V, medial lamina VII, medial lamina VIII, lateral laminae V
      and VI and lateral laminae VIII and IX. Properties of main components in
      antidromic field potentials recorded in each of areas have been described. The
      presumable termination sites of axons of investigated cellular groups are
      considered.

PMID- 7817840
TI  - Changes in cortical and hippocampal EEG activity accompanying spontaneous
      electrocortical seizures in rats.
AB  - The purpose of the present study was to find out whether the occurrence of bursts
      of spontaneous spike-wave discharges (SWD) in rat neocortex is related to a
      particular state of vigilance (level of arousal), as some authors suggested, or
      rather to transitions from one state to another as postulated by others. Patterns
      of cortical and hippocampal EEG preceding and following the SWD bursts were
      studied in rats. It has been found that the beginning of an SWD episode is
      usually preceded by a shift of cortical activity toward synchronization and
      replacement of the rhythmic slow activity (RSA) in the hippocampus by large
      irregular activity (LIA). After SWD, the cortical activity is usually more
      desynchronized and RSA is present more frequently than just before its onset. An
      analysis of selected episode-free and episode-rich EEG segments revealed that
      SWD's occur in abundance at the periods characterized by frequent changes of the
      hippocampal EEG pattern but are absent during the periods in which long-lasting
      RSA trains dominate in the record. Thus, the data confirm that SWD occurrence is
      related more to transitions from one state to another than to a particular state
      as such. They also indicate that the preferable conditions for SWD's appear when
      arousal is decreasing from a moderate to a lower level.

PMID- 7817841
TI  - The effects of lesions of the bed nucleus of the stria terminalis on sodium
      appetite.
AB  - Lesions of the bed nucleus of the stria terminalis result in decrements in sodium
      ingestion. Specifically, sodium ingestion that is aroused by mineralocorticoids,
      in addition to sodium depletion, was reduced in rats with large lesions of the
      bed nucleus of the stria terminalis. Need-free salt ingestion was also reduced.
      These results suggest that the bed nucleus of the stria terminalis may be
      involved in the regulation of sodium appetite.

PMID- 7817842
TI  - The oblique effect in the human somatic sensory system.
AB  - Blindfolded, sitting subjects were asked to feel whether two bars were parallel
      or not. In 50% of the presentations the bars were parallel to each other. In all
      presentations either one or two bars were oriented vertically, horizontally, 45
      degrees or 135 degrees. In this situation the best accuracy was found when the
      bars were vertically and horizontally oriented in space. The experiments were
      repeated with the subjects tilted laterally by 45 degrees. Now the best accuracy
      was found when the bars were at an angle of 45 degrees or 135 degrees to the
      length-axis of the body. This means that the oblique effect in the somatic
      sensory system is of vestibular origin.

PMID- 7817843
TI  - Effect of sodium tellurite on the myelogenesis in the rat CNS.

PMID- 7817844
TI  - Cerebral lateralization in a deaf child as related to earlier auditory
      experiences.

PMID- 7817845
TI  - [Classification of mental diseases. From Bertillon to CID-10: a century of
      international collaboration].
AB  - The first International Classification of Diseases (ICD) was approved during the
      Congress of the Statistical International Institute, in Chicago, in Paris, in
      1893. It was based on a list of diseases prepared by Jacques Bertillon. Minor
      changes were introduced in this classification during decennial revisions made at
      international meetings and it remained in use until 1948, when the World Health
      Organization's Provisional Committee was charged with the task of producing ICD
      6. ICD-6 represented a major shift from the previous internal conceptualization,
      particularly in what concerns the Chapter V., dealing with mental disorders. From
      1955 on WHO produced with approximately a 10-year interval ICV-7, 8, and 9. Few
      modifications in relation to ICD-6 were introduced by these revisions, except for
      the introduction of a glossary of terms in the chapter on mental disorders. This
      glossary had a major impact towards the development of a common language in
      psychiatry. Based on epidemiological findings, and based also on an intensive and
      extensive international network of clinicians and investigators, ICD-10 was
      published in 1992. It represented a substantial improvement regarding the
      conceptualization of the classification of mental disorders, in relation to
      previous revisions of the ICD. Future tasks relating to ICD-10 include training
      of health personnel for its proper utilization, in addition to finalizing further
      ICD-10 versions, e.g. for research purposes and for primary health care use.

PMID- 7817846
TI  - [Lack of involuntary abnormal movements in untreated schizophrenic patients].
AB  - Drug-naive schizophrenic patients lacked abnormal involuntary movements. Chronic
      neuroleptic treatment was associated in 4% of the cases with Tardive Dyskinesia
      (TD). These findings suggest that schizophrenia, at least in its early stages, is
      not contributing to the appearance of Tardive Dyskinesia, and also underscore the
      importance of using the lowest effective neuroleptico dose to reduce the risk of
      that syndrome.

PMID- 7817847
TI  - [Reactivity to stress as a modular factor in psychopathology].
AB  - The relationship between Stress Reactivity and psychopathology, mainly minor
      psychopathology, in a sample of medical students (n = 76) to whom the Stress
      Reactivity Questionnaire (CRE-32) and Derogatis' SCL-90-R Questionnaire (Symptom
      Checklist 90 Revised) were administered, is studied. A higher psychopathological
      distress, as evidenced in SCL-90-R general psychopathological indexes and
      psychopathological dimensions scores, is reported by subjects with high stress
      reactivity compared to those with low stress reactivity (p < 0.001). These
      results suggest that stress reactivity acts as a buffer of psychopathology. Thus,
      the assumption of the participation of a "high stress reactivity" in facilitating
      illness in general, both in psychiatric conditions as in medical ones, is
      discussed.

PMID- 7817848
TI  - [Endogenous and neurotic depression again III: support for a sequence
      hypothesis].
AB  - The sequential hypothesis about depression tells: "neurotic" and "endogenous"
      depression are not different diseases, but two different moments in the evolution
      of a unique disorder (initial and terminal, respectively). The authors use Kiloh
      and Garside's (1963) and Carney et al's (1965) data to support this hypothesis.
      The bibliographic data are analyzed in that way to show that biological
      correlates of endogeneity are the final pathway of an ontogenic evolution of
      biological modifications in depression less obvious in initial episodes
      ("neurotiforms") and more evident in subsequent episodes ("endogeniforms").

PMID- 7817850
TI  - [Schizophrenia models: a review of the hypothetical pathologic processes
      underlying phenomenological manifestations].
AB  - Since Kraepelin and Bleuler consolidated the concepts of dementia preacox and
      schizophrenia almost a century ago, the heterogeneity of the disorder has been
      recognized as a problem. Since the germinal contribution of Crow, two different
      processes underlying positive and negative symptoms have been intensively
      studied. However, there are data that suggest the existence of four underlaying
      pathological processes to schizophrenic phenomenology: positive, negative,
      disorganisation and relational, the former three processes being of
      physiopathological nature and the disorders of relating having a psychological
      character. Other symptomatological dimensions such as subjective cognitive
      disorders and catatonic phenomena deserve further research.

PMID- 7817849
TI  - [The female role as assessment of mental health of women within 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- 7817851
TI  - [History of psychiatry].

PMID- 7817852
TI  - [Nephritic colic. Analysis of 140 cases].
AB  - A nephritic colic is one of the most common pictures of urologic conditions, a
      primary causes being the occurrence of lithiasis concretions along the urinary
      tract. A series of 140 cases of nephritic colic diagnosed in the emergency ward
      and later referred to our office for follow-up are presented here. The relevance
      of the physical examination is emphasized, pointing out that with practice the
      simple performance of abdominal X-ray, ultrasound and urinary sediments is
      usually enough to reach a certainty diagnosis. There is, however, near 10% cases
      where it is necessary to carry out contrast studies or endoscopic manoeuvres to
      be able to differentiate a nephritic colic from other conditions. The primary aim
      of treatment is to overcome pain, facilitate the advance of the lithiasis
      obstacle and to preserve the renal function. A description is made of the various
      drugs used, while endoscopic manoeuvres are reserved for the more selected cases
      of compromised kidney or when the patient's general condition so requires.

PMID- 7817853
TI  - [Kidney transplantation in patients over 60 years of age. Study of 37 patients].
AB  - Between February 1975 and September 1993, 735 renal transplantations have been
      performed 37 of which took place in 60+ year-old subjects. All grafts were from
      corpse donors. 34 were first time transplants and 3 were re-transplants. In
      general, immunosuppression has been accomplished with Cyclosporin, Azathioprine,
      and Prednisone. Annual patient and graft survival is 87% and 69%, respectively. A
      review is made of the complications developed and the success rate with and
      without a functioning graft. Considering long-term results, many patients lead a
      normal live with stable renal function.

PMID- 7817854
TI  - [Cancer and kidney transplantation].
AB  - The higher risk of developing malignant tumours in transplanted patients is a
      fact widely acknowledged over the last decade. This paper includes an analysis of
      our series and a review of the literature. Cancers developed by the transplanted
      patient or "de novo" cancers and, within this group skin and lip cancer (58%),
      are by far the most frequent ones. Their biological behaviour is, in general,
      more aggressive than similar ones in non-transplanted population. Also, different
      incidence rates and behaviour have been established depending on the
      immunosuppressive regime given to the patient. Most common pre-existing carcinoma
      was renal cancer (one third of cases). When these patients had been adequately
      treated before the transplant, the minimum disease-free interval that has to
      elapse to be included in a waiting list will depend on the type of tumour.
      Transferred tumours are the least frequent but more worrying ones due to both
      their clinical and legal implications. In view of the existing evidence, it is of
      particular relevance to insure the primitive nature of any CNS tumour as well as
      the absence of tumoral disease in young females who die of brain haemorrhage.

PMID- 7817855
TI  - [Diverticulum of the female urethra. Review of the literature].
AB  - Presentation of nine cases of diverticulum of the female urethra, and assessment
      of their specific features both clinical and diagnostic, as well as the surgical
      techniques used in their management. Review of the literature with regard to
      incidence, etiopathogeny and presentation of this condition. Analysis of the
      different diagnostic procedures available to show the presence of an urethral
      diverticulum and the various management options currently used in their
      resolution.

PMID- 7817856
TI  - [Leydig cell tumor. Comments on 5 cases].
AB  - Leydig's cells tumours are a variant of testicular tumours. Its has a low
      incidence, accounting for just 1-3% of all testicular tumours. This tumour is
      characterized by its endocrine manifestations, and it is an element in the
      differential diagnosis of many endocrine sexual dysfunctions both in adults and
      children, due to the tumour's capacity to secrete hormones. This paper
      contributes 5 cases of Leydig's cells tumours diagnosed in our hospital between
      1977 and 1993.

PMID- 7817857
TI  - [Conn's syndrome].
AB  - Adrenal hypertension is an uncommon phenomenon. When seen in association with
      hypokalemia the existence of primary aldosteronism, the most frequent cause of
      which is an adenoma of the adrenal gland cortex, should be suspected. This paper
      contributes one case of primary aldosteronism treated by unilateral resection of
      the adrenal adenoma, with no surgical complications and good medium-term results.

PMID- 7817858
TI  - [Rescue of infected penile prosthesis: initial experience with prosthesis
      conservation].
AB  - Fitting a penial prosthesis has become an effective procedure to treat sexual
      impotence. However, its main complication, infection, remains a relatively
      frequent problem which forces the implant removal with the resulting treatment
      failure. This paper summarizes our early experience in 4 patients with infected
      penial prosthesis, who were treated by correcting the patient's general status,
      adequate antibiotic treatment, and deep and regular curing of the infected area.
      In these 4 patients, we managed to preserve the implant, achieving an adequate
      functional and cosmetic result. The paper discusses the pathophysiological
      mechanisms which would explain these improvements and points to the eventual
      indications and contraindications of the treatment. Finally, a recommendation is
      made to use this treatment with caution since our experience was still
      preliminary.

PMID- 7817859
TI  - [Bladder compression caused by hip prosthesis displacement].
AB  - Case report of one patient with extrinsic vesical compression secondary to a
      displaced hip prosthesis. Interesting case due to increasing hip prosthesis
      surgery over the last few years involving, although not frequently, ureteral and
      vesical injuries of varying consideration which require early diagnosis and
      management.

PMID- 7817860
TI  - [Fibroepithelial polyp of the ureter].
AB  - Exposition of one case of fibroepithelial polyp of the ureter in a young male
      patient. The interest of the case lies in the rarity of this entity. Review of
      all likely etiologies, clinical presentations and differential diagnosis, mainly
      with malignant tumours whose prognosis and treatment are entirely different.
      Endoscopic approach and surgical removal of the polyp and its base are the
      therapeutical choice for this type of neoformations.

PMID- 7817861
TI  - [Malignant mesothelioma of the tunica vaginalis of the testis].
AB  - We report a case of malign mesothelioma of the tunica vaginalis of testis in a 84
      years-old male. Clinical presentation was hydrocele. Special attention is given
      to differential diagnosis and therapeuticals possibilities.

PMID- 7817862
TI  - [Prostatic signet ring cell carcinoma].
AB  - Presentation of one case of prostate carcinoma of "signet ring" cells. Review of
      its clinical evolution, explaining the histological and histochemical findings,
      so as to contribute more data with regard to prognosis and composition of those
      cells. Update and comparison of various authors' views, which are explained for
      discussion.

PMID- 7817863
TI  - [Cerebral metastasis as first manifestation++ of a bladder carcinoma].
AB  - The infiltrant vesical carcinoma shows a tendency to become metastatic in a high
      percentage of cases, so that the preferred sites are usually the retroperitoneal
      lymph nodes, liver and bone. CNS metastasis is an uncommon fact, but it is even
      less common to find CNS affectation symptoms even before the appearance of any
      signs and symptoms related to the vesical affectation itself. Contribution of one
      case of infiltrant vesical carcinoma which presented with focal neurological
      symptomatology as its first manifestation.

PMID- 7817864
TI  - [Involvement of cranial pairs as manifestation of prostatic cancer].
AB  - Two cases of prostate cancer (PC) which presented clinically with affectation of
      the cranial pairs due to skull base metastasis. In both cases, existence of
      intraparenchimatous brain metastasis was excluded. Initial improvement with
      hormonal therapy was followed by clinical, analytical and radiological relapse
      due to spread of process until death, at 11 and 36 months from diagnosis.
      Although PC's bone metastasis are frequent, their location at the skull base is
      uncommon. Even more rare are the cases which present with changes in the cranial
      pairs in the absence of signs and symptoms of prostatism.

PMID- 7817865
TI  - [Cyst of the ejaculatory duct].
AB  - Presentation of a new case of cyst of the ejaculatory duct, diagnosed in a 49
      year-old patient. Unspecific symptomatology, with hemospermia and urethrorrhagia
      of 6 months evolution. Diagnosis is reached by abdominal and transrectal
      ultrasound and deferent-vesiculography. Computerized Axial Tomography and
      Magnetic Nuclear Resonance are performed to document the case and for subsequent
      follow-up. No other associated malformations are found. Following failure of
      endoscopic surgery, the original approach, abdominal exeresis is performed with
      excellent evolution both in the immediate post-operative and at 1-year follow-up.
      Likely etiology and differential diagnosis from other male pelvic cysts are
      discussed. List of references on differential diagnosis and published cases in
      included.

PMID- 7817866
TI  - Glutathione S-transferases: structure and mechanism of an archetypical
      detoxication enzyme.

PMID- 7817867
TI  - Microtubule dynamics: bioenergetics and control.

PMID- 7817868
TI  - Expression of the alpha-crystallin/small heat-shock protein/molecular chaperone
      genes in the lens and other tissues.

PMID- 7817869
TI  - Phosphoenolpyruvate carboxykinase (GTP): the gene and the enzyme.

PMID- 7817870
TI  - Regulation of cholesteryl ester hydrolases.
AB  - Recent developments in understanding the biochemical and molecular nature of the
      CE hydrolases and their impact on cellular cholesterol trafficking have further
      defined the enzyme's mechanism of action with reasonable clarity. The
      availability of the cDNA probe for the human lysosomal acid lipase/CE hydrolase
      and the hormone-sensitive lipase now makes it possible to study CE hydrolase gene
      regulation and expression in human tissue; and it can now be stated with more
      assurance that the cytoplasmic CE hydrolase (NCEH) is most likely activated
      through phosphorylation by the cyclic AMP-dependent protein kinase. Evidence also
      shows that the NCEH is most likely identical to the hormone-sensitive lipase and
      that it plays an important role in cholesterol efflux properties of the cell.
      Recent advances in the discovery of the role of the eicosanoid/cytokine network
      in the regulation of CE hydrolysis, highlighted in Figure 10, further emphasize
      the interesting but complex nature of the cholesterol trafficking processes in
      cells, particularly under pathophysiological conditions such as cell injury,
      repair, and inflammation. It can be speculated that in several years, when the
      crystal structure of the CE hydrolase is known, the structure-function properties
      of this enzyme's catalytic domain, as it relates to the physical state of the CE
      substrates, should further clarify the precise role of this enzyme in
      intracellular cholesterol mobilization and trafficking under a variety of
      cellular conditions.

PMID- 7817871
TI  - The new biology of adenosine receptors.

PMID- 7817872
TI  - Pararetroviruses and retroviruses: a comparative review of viral structure and
      gene expression strategies.

PMID- 7817873
TI  - Rotaviruses: immunological determinants of protection against infection and
      disease.
AB  - Although studies of rotavirus immunity in experimental animals and humans have
      often yielded conflicting data, a preponderance of evidence supports the
      following answers to the questions initially posed. 1. What is the importance of
      virus serotype in formulating an optimal vaccine? Both vp4 and vp7 induce virus
      neutralizing antibodies after either natural infection or immunization; the
      capacity of vp4 to induce rotavirus-specific neutralizing antibodies is probably
      greater than that of vp7. However, protection against disease after immunization
      of infants and young children is induced by strains heterotypic to the challenge
      virus (e.g., immunization with WC3 induces protection against disease induced by
      serotypically distinct human G1 strains). In addition, oral inoculation of
      infants with primate or bovine reassortant rotaviruses containing genes that
      encode human vp7 has not consistently induced a higher level of protection
      against challenge than that induced by parent animal rotaviruses (see Table I).
      Therefore, although vp4 or vp7 or both are probably important in inducing
      protection against challenge, it has not been clearly demonstrated that inclusion
      of the epidemiologically important human (as distinct from animal) P or G type is
      important in protection against human disease. 2. Which immunological effector
      arm most likely protects against rotavirus disease? No immunological effector arm
      clearly explains protection against heterotypic challenge. Protection against
      disease is not predicted by rotavirus-specific neutralizing antibodies in serum.
      Rotavirus-specific, binding sIgA in feces [detected by enzyme-linked
      immunosorbent assay (ELISA)] induced after natural infection does correlate with
      protection against disease induced by subsequent infection. However, protection
      after immunization with WC3 may occur in the absence of a detectable fecal sIgA
      response. The relationship between rotavirus-binding sIgA and sIgA-mediated
      neutralizing activity directed against the challenge virus remains to be
      determined. Binding rotavirus-specific sIgA in feces detected by ELISA may only
      be a correlate of other events occurring at the intestinal mucosal surface. The
      presence of broadly cross-reactive, rotavirus-specific CTLs at the intestinal
      mucosal surface of mice acutely after infection is intriguing. It would be of
      interest to determine the degree to which the presence of cross-reactive,
      rotavirus-specific CTLs in the circulation is predictive of the presence of virus
      specific CTLs among intestinal lymphocytes and protection against challenge.
      Unfortunately, studies of virus-specific CTLs are difficult to perform in
      children. 3. By what means is virus antigen best presented to the host to elicit
      a protective immune response? Oral inoculation may not be necessary to induce a
      protective, virus-specific immune response at the intestinal mucosal
      surface.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7817874
TI  - Human immunodeficiency virus type 1-associated CD4 downmodulation.

PMID- 7817875
TI  - Antisense treatment of viral infection.
AB  - In this chapter I have attempted to outline the rationale that underlies the
      antisense approach to treatment of virus infection, to catalog the effector
      molecules that are currently available, and to estimate the relative worth of
      each. In so doing I have tried to describe the criteria that might be employed in
      their design and the factors that may determine their efficacy in tissue culture
      and, perhaps, in vivo. Finally, I have described the few examples presently
      available that indicate that antisense approaches may one day be therapeutically
      useful in treatment of disease of viral or nonviral origin.

PMID- 7817876
TI  - The structure, function, and regulation of papillomaviral genes in infection and
      cervical cancer.

PMID- 7817877
TI  - Equine herpesviruses 2 and 5: comparisons with other members of the subfamily
      gammaherpesvirinae.

PMID- 7817878
TI  - Molecular biology of tombusviridae.

PMID- 7817879
TI  - SpV1 and SpV4, spiroplasma viruses with circular, single-stranded DNA genomes,
      and their contribution to the molecular biology of spiroplasmas.

PMID- 7817880
TI  - Molecular biology of rubella virus.

PMID- 7817881
TI  - New ideas to improve the shape of the ala of the Oriental nose.
AB  - The Oriental nose is smaller and lower than that of Caucasians. The lobule, the
      movable lower third, is lower and wider when compared with the Caucasian nose,
      and this region, including the tip, is entirely round. Traditionally, the
      isosceles triangle of the basal view, which consists of the nasal tip, the
      columella, and the alae surrounding the nostril, has been used to show the
      differences between the two races. Alae form two sides of the isosceles triangle
      and have the greatest influence on the shape of the basal view. For Orientals,
      the distance between the sides of the alar base is large, and the alae themselves
      are round and extrude laterally. Aesthetically, this shape cannot be seen as
      beautiful, and various methods have been applied to correct these deficiencies.
      However, no one has ever reported a method that directly corrects the shape of
      alae that extrude laterally. The author has found the technique of correcting the
      middle part of the ala without leaving any external scars by performing some of
      the plasties from inside the ala or by grafting cartilages. Successful results
      have been obtained and are reported here.

PMID- 7817882
TI  - Nasal septal perforations must and can be closed.
AB  - In this time of increasing occurrence of septal perforations caused by cocaine
      abuse, the plastic surgeon who deals mainly in rhinoplasty must learn to treat
      these defects with sophisticated methods. Too many septal perforations,
      especially large ones, are not treated because the surgical techniques are
      difficult. This article describes and illustrates two methods that close all
      kinds of perforations. Local flaps should be considered obsolete. A perforation
      up to 4 cm in diameter must be repaired in one step. This includes wide
      dissection of the mucoperichondrium and mucoperiosteum, suture of the hole on
      both sides, and interposition of parietal fascia or cartilage, sometimes with the
      help of bilateral small buccal flaps to cover the gap between the columella and
      the dissected mucoperichondrium containing the closed perforation on both sides.
      For closure of perforations greater than 4 cm in diameter, a three-step procedure
      which uses a composite three-layered buccal flap including ear concha cartilage
      is described. In the second step, the spoon-shaped flap is fed into the nasal
      cavity to fill the septal defect. The third step divides the pedicle. In many
      cases a unilateral or bilateral alotomy or the section of the columellar base may
      facilitate the suture of the flaps.

PMID- 7817883
TI  - Calibrated nasal tip: review of 100 cases.
AB  - Asymmetry of the alar cartilages is a common finding in primary rhinoplasty in
      Caucasian patients. The "delivery" technique provides good exposure of the alar
      cartilages which allows examination and tailoring in better surgical conditions
      than those of the "closed" technique and also avoids the "open" nose approach in
      the majority of rhinoplasty cases.

PMID- 7817884
TI  - Endoscopic full facelift.
AB  - This article demonstrates the efficacy of endoscopic techniques in total facial
      rejuvenation. The author has introduced the total subperiosteal dissection to the
      endoscopic forehead lift. This concept has been extended to the rejuvenation of
      the central and lower third of the face. Patients up to the late 40s can have a
      total facelift without skin excisions. In older patients, the introduction of
      endoscopic techniques helps to minimize some of the undesirable sequelae of the
      traditional open procedures such as alopecia, scalp paresthesias, and facial
      edema of the subperiosteal lift. The author also introduces a new, more
      efficacious method of midface suspension.

PMID- 7817885
TI  - The fiber endoscope with guidable and flexible working instruments for
      endofacelift: a new instrument in facial surgery.
AB  - The use of endoscopic video-assisted technique in facial rejuvenation is one of
      the most recent advances in aesthetic plastic surgery of the face. It replaces
      the bicoronal incision without the necessity of skin resection. The idea is to
      detach the muscles from the periorbital attachment, forcing the occipital muscle
      to pull the forehead tissue back and thus elevating the eyebrows. Therefore, we
      developed a flexible fiber endoscope that allows the surgeon to guide flexible
      instruments through its working channel. The endoscope is introduced through a 1
      cm midscalp incision so that it can be used to expose and treat soft tissue
      regions in the forehead, the midface, and the neck.

PMID- 7817886
TI  - Endoscopic augmentation mastoplasty.
AB  - The authors present their experience with breast augmentation using endoscopy.
      They use an axillary approach to insert inflatable breast implants above the
      pectoralis muscle. The advantages of this method are that it is more comfortable
      to the patient, recovery is faster, it leaves no scars on the breasts, and there
      is no change in sensation.

PMID- 7817887
TI  - Use of pubic fat as a graft for eyelid defects.
AB  - This article suggests that pubic fat be used as a graft for repair of eyelid
      defects such as when the eye is too hollow since donor sites for eyelid grafts
      are limited. Pubic fat is granular and has smaller lobules. Therefore, it was
      more likely to hold its shape when filling in a congenitally hollow lid. In our
      case report, a biopsy at 3.5 years shows the viability of this graft.

PMID- 7817888
TI  - Anatomical basis for a safe and easier approach to composite rhytidectomy.
AB  - The authors present the anatomical findings that have made an easier approach to
      composite rhytidectomy possible. The lower lateral border of the orbicularis
      oculi muscle (OOM) overlies the zygomaticus major muscle (ZMM), the upper third
      of which tightly adheres to the malar bone. The OOM is innervated throughout over
      its circumference by a plexus of small facial nerve branches. From its deeper
      surface, the ZMM is innervated by two to four branches in its upper third and
      middle third. These branches are jeopardized in an extended sub-SMAS dissection
      as this tends to go deep into the ZMM. The malar fat pad is superficial to the
      SMAS layer that invests the zygomaticus and levator labii muscles and, with age,
      tends to slide downward, medially deepening the nasolabial folds. An extended
      dissection beyond the OOM tends to remain superficial to the upper part of the
      ZMM, zygomaticus minor, and levator muscle complex. We have found that extending
      the suborbicularis dissection inferiorly and laterally offers three major
      advantages: (1) The correct deep subcutaneous plane just above the ZMM,
      zygomaticus minor muscle, and levator complex can be found easily, leaving all of
      the fat attached to the skin. The only structures at risk are some minor motor
      branches to the OOM that can be divided without any morbidity because of the
      extensive plexiform innervation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7817889
TI  - Copious lactation following augmentation mammaplasty: an uncommon but not rare
      condition.
AB  - The senior author encountered many patients who experienced copious galactorrhea
      following augmentation mammaplasty and yet there are only four cases reported in
      the medical literature. A retrospective chart review of 1,000 breast augmentation
      patients operated on by the same surgeon under general anesthesia revealed eight
      documented cases of copious postaugmentation lactation. The lactation started an
      average of 6.6 days following surgery and was self-limited with an average
      duration of 5.2 days. The charts of the patients who lactated were studied in
      detail for possible contributing factors. Eight controls, matched for age, race,
      parity, implant type, implant size, hormonal therapy (birth control pill),
      surgical incision, and prosthesis placement site, were similarly studied and
      statistical analysis performed on the differences between these two groups of
      patients. The only statistically significant factor found between the groups was
      gravidity (P value < 0.03). One patient who lactated postoperatively was
      nulliparous. The postoperative occurrence of lactation does not increase
      postoperative morbidity. Presenting characteristics, possible contributing
      factors, and other multifactorial causes of this uncommon postoperative
      occurrence are discussed.

PMID- 7817890
TI  - Asymmetry of the breast: some uncommon cases.
AB  - The incidence of breast asymmetry is not well known. A review of 500
      mastoplasties showed that we have treated 26 cases (5.2%) of significant
      asymmetry. Most of the uneven breasts are rather common cases and can be
      corrected with routine techniques of reduction and augmentation mammaplasties. In
      only a few patients is the malformation so pronounced that it requires more
      elaborate corrective methods. We present six of these cases.

PMID- 7817891
TI  - Liponecrotic cysts after augmentation mammaplasty with fat injections.
AB  - A 26-year-old woman underwent breast augmentation with fat injections from
      trochanteric liposuction. After one year firm lumps developed in both breasts.
      Surgical treatment included excising the cysts through an inframammary approach.
      Volume replacement consisted of a silicone gel prosthesis inserted through an
      axillary retropectoral approach. In a second stage, a supra-areolar dermopexy was
      done to centralize the nipple-areola complex.

PMID- 7817892
TI  - Surgical treatment of mandibular prognathism in collaboration with orthodontic
      treatment in Korea.
AB  - Mandibular prognathism is defined by John Hunter as follows: "The lower jaw
      projecting too far forward so that the foreteeth pass before those of the upper
      jaw, therefore disfigurement and malocclusion are two of the main facial
      characteristics." Other distinguishing features are the coexistence of class III
      malocclusion, incomplete closure of lip, deviation of the midline, and decrease
      of labiomental fold. Generally, the functional occlusal relationship and balanced
      facial harmony cannot be obtained by surgical or orthodontic treatment alone. Its
      success depends on careful conjoint, supplementary diagnostic, and treatment
      planning. As a cardinal principle the authors made the following combined
      surgical and orthodontic treatment plans: (1) Orthodontic treatment relocates and
      decompensates the malpositioned teeth (remove the masking effect of teeth) and,
      therefore, skeletal deformity is exposed maximally. (2) Surgical treatment
      eliminates the maximally exposed skeletal defect. Therefore, dramatic facial
      balance and functional occlusal relationship are obtained. Treatment planning
      includes the pre- and postoperative orthodontic treatment, lateral cephalometric
      prediction tracing (LCPT), and model surgery with dental cast. The authors made
      it easy with the use of an acrylic dental wafer to coordinate exact occlusal
      relationship after surgery. We treated mandibular prognathism by using Dautrey's
      modification of the sagittal split ramus osteotomy (SSRO) (10 cases) and
      intraoral vertical ramus osteotomy (IVRO) (5 cases) and sometimes additional
      genioplasty (2 cases). IVRO was used in those cases where (1) the amount of
      setback was more than 10 mm and (2) where there was a flat gonial angle.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7817893
TI  - Effects of a positively charged biomaterial for dermal and subcutaneous
      augmentation.
AB  - Based on previous experimental connective tissue work, the use of a positively
      charged dextran-based biomaterial in subcutaneous tissue sites was evaluated.
      After hydration with saline, the biomaterial was injected beneath the abdominal
      skin in rats. A robust macrophage response was initially seen at 30 days without
      acute inflammation. By one year postoperatively, extensive intermaterial
      fibroblast and collagen ingrowth had occurred. No evidence of a foreign-body or
      chronic inflammatory response was seen. These preliminary findings suggest good
      tissue compatibility of this biomaterial and suggests that when combined with a
      biocompatible liquid medium, the potential for development of a bioactive dermal
      and subcutaneous injectable substance exists.

PMID- 7817895
TI  - Monoclonal antibodies directed against tick-borne encephalitis virus with
      neutralizing activity in vivo.
AB  - Monoclonal antibodies (MoAbs) were raised against the tick-borne encephalitis
      (TBE) virus, strain K23. The reactivities of 14 selected MoAbs were characterized
      by ELISA, Western blot analysis, haemagglutination inhibition,
      immunoprecipitation, in vivo protection and in vitro neutralization tests. All
      MoAbs reacted only with the glycoprotein E. The binding epitope of one MoAb could
      be delimited by a synthetic peptide to amino acids 306-339 representing one
      immunodominant loop structure of the glycoprotein E. The MoAbs exhibited
      individual reactivities against 13 different TBE virus isolates in ELISA and
      immunoblot test ranging from type-specific reactions to a broad reactivity with
      all isolates. Four MoAbs also showed a cross-reaction with other flaviviruses
      like West Nile virus and/or Yellow fever virus in immunoblot analysis. By
      competition ELISA the MoAbs could be divided into five different reaction
      patterns. Four MoAbs showed neutralizing activity with titers in the range 1:140
      to 1:5,000 in an in vitro assay. These neutralizing activities could be confirmed
      by an in vivo mouse challenge model. The MoAbs are useful for diagnostic purposes
      and for differentiation of TBE virus strains and other flaviviruses.

PMID- 7817894
TI  - Reverted virulence of attenuated tick-borne encephalitis virus mutant is not
      accompanied with the changes in deduced viral envelope protein amino acid
      sequence.
AB  - Serial passages of tick-borne encephalitis (TBE) virus strain 4387 isolated from
      the liver and lungs of the bank vole through the salivary glands of Ixodes
      ricinus ticks led to a reduction of its virulence for laboratory mice infected
      via peripheral route. When attenuated mutants were passaged through mouse brains,
      virulent phenotypes have appeared in the 3rd mouse passage. After 5 consecutive
      passages the virus was more pathogenic for mice after peripheral inoculation than
      the parental 4387 strain. The nucleotide sequence of the envelope proteins of the
      strain 4387 was studied after passaging through ticks salivary glands and
      subsequently through mice. The sequences coding for the envelope protein E of the
      virus from the first, third and fifth mouse passages were compared with those of
      parental virus and mutant attenuated in ticks. The attenuated mutant differing
      from the parental strain 4387 by the amino acid substitution from glutamic acid
      to lysine at position 84, and from isoleucine to threonine at amino acid position
      319 revealed strongly reduced pathogenicity for adult laboratory mice after
      peripheral inoculation. The attenuated mutant regained its virulence after 3 - 5
      mouse brain passages, but the two amino acid substitutions were still conserved.

PMID- 7817896
TI  - Replication and persistence of murine herpesvirus 72 in lymphatic system and
      peripheral blood mononuclear cells of Balb/C mice.
AB  - After intranasal inoculation of murine herpesvirus 72 (MHV-72) to Balb/c mice the
      virus persisted in adherent lung mononuclear cells (AMC). Infectious virus was
      occasionally detected during a period of eight months after infection in
      lymphatic organs (thymus, spleen, lymph nodes), bone marrow, alveolar and
      peritoneal AMC, and lymphocytes and macrophages of peripheral blood by indirect
      immunofluorescence and cocultivation with permissive VERO cells. Mouse B-cell
      lines NS0 and SP2/0 were permissive for MHV-72 infection when inoculated in
      vitro. Virus-neutralizing antibodies have been detected during one year period in
      the sera of infected mice, and their levels correlated with activation of the
      latent MHV-72.

PMID- 7817897
TI  - Experimental studies on the susceptibility of domestic pigs to West Nile virus
      followed by Japanese encephalitis virus infection and vice versa.
AB  - A study on the susceptibility of domestic pigs to West Nile virus (WNV) and
      Japanese encephalitis virus (JEV) infection was carried out. One batch of pigs
      was inoculated with WNV followed by JEV and another batch was inoculated vice
      versa. The first batch developed low level of viraemia and haemagglutination
      inhibition (HI) antibodies to both viruses. There was a booster effect on the
      already existing WNV antibodies after challenging with JEV. In the second batch
      the animals developed high level of JE viraemia but did not develop WN viraemia.
      They developed HI antibodies to both JEV and WNV with low booster effect of WNV
      infection on JEV antibodies. Fresh batches of pigs were infected through bite of
      WNV- and JEV-infected Culex vishnui mosquitoes. WNV-infected pigs did not show
      viraemia, whereas JEV-infected ones developed JE viraemia. The study indicated
      that pigs were poor hosts for WNV but good ones for JEV. However, WNV antibodies
      reduced the level of JE viraemia and JEV infection boosted the already existing
      WNV antibodies.

PMID- 7817898
TI  - Effect of ammonium chloride on multiplication of rinderpest virus in Vero cells.
AB  - Ammonium chloride, a lysosomotropic weak base, inhibited replication of
      rinderpest virus in Vero cells. The inhibition of replication was dose-dependent
      and the minimum effective dose of ammonium chloride was determined as 5-10
      mmol/l. The fusion efficiency and the yield of both cell-free and cell-associated
      virus were reduced in the presence of the inhibitor. Western blot analysis of
      rinderpest virus-infected Vero cells revealed that synthesis of two virus-induced
      polypeptides were affected by the presence of ammonium chloride.

PMID- 7817899
TI  - Demonstration of antibodies against foot and mouth disease virus (FMDV) type O
      and Asia-1 in non-descriptive crossbred calves.
AB  - Sera from non-descriptive crossbred calves were screened for the presence of
      neutralizing antibodies against FMDV type O and Asia-1 for a period up to 215
      days. The antibody titer of 16 remained constant up to 215 days against type O
      and up to 190 days against type Asia-1 virus in some animals. In majority of the
      animals the antibody titers remained constant up to three months. The possible
      reason for a frequent breakdown of immunity in the vaccinated animals even 3-4
      months after vaccination could be the fact that the calves were vaccinated
      repeatedly at their very early age with an ill effect of immunization in the
      presence of persisting antibodies.

PMID- 7817900
TI  - Truncated tau protein as a new marker for Alzheimer's disease.
AB  - Molecular analysis of histological hallmarks (neurofibrillary tangles, neuritic
      plaques, neuropil threads and dystrophic neurites) of Alzheimer diseased brain
      tissues showed that these lesions contain paired helical filaments. Their major
      constituent is microtubule associated protein tau that is in an abnormally
      hyperphosphorylated and truncated state. These diseased forms of tau protein are
      unable to promote full microtubule assembly. Understanding of the molecular basis
      of the processes leading to the modifications of tau proteins and paired helical
      filament formation will form a firm step toward rational drug development and the
      cure of the Alzheimer's disease.

PMID- 7817901
TI  - Analysis of the amino sugar composition of Chlamydia psittaci lipopolysaccharide.

PMID- 7817902
TI  - Transradial artery coronary angioplasty.
AB  - This study explored the feasibility and safety of percutaneous coronary balloon
      angioplasty (PTCA) with miniaturized PTCA equipment via the radial artery.
      Coronary angioplasty (PTCA) via the femoral or brachial arteries may be
      associated with rare vascular complications such as bleeding and damage to the
      artery and adjacent structures. It was postulated that PTCA via the radial artery
      with miniaturized angioplasty equipment is feasible and that no major puncture
      site-related complications occur because hemostasis is obtained easily and
      because no major structures are near the radial artery. With double blood supply
      to the hand, radial artery occlusion is well tolerated. In 100 patients with
      collateral blood supply to the right hand, PTCA was attempted with 6F guiding
      catheters and rapid-exchange balloon catheters for exertional angina (87
      patients) or nonexertional angina (13 patients). Angioplasty was attempted in 122
      lesions (type A n = 67 [55%], Type B n = 37 [30%], and type C n = 18 [15%]). Pre-
      and post-PTCA computerized quantitative coronary analysis was performed. Radial
      artery function and structure were assessed clinically and with Doppler and two
      dimensional ultrasound on the day of discharge. Coronary catheterization via the
      radial artery was successful in 94 patients (94%). The 6 remaining patients had
      successful PTCA via the femoral artery (n = 5) or the brachial artery (n = 1).
      Procedural success (120 of 122 lesions) was achieved in 92 patients (98%) via the
      radial artery and in 98 patients of the total study population.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7817903
TI  - Doppler echocardiographic pulmonary venous flow-velocity pattern for assessment
      of the hemodynamic profile in acute congestive heart failure.
AB  - The hemodynamic profile of congestive heart failure (CHF) is best described in
      terms of its two primary sets of hemodynamic parameters, that is, left atrial
      pressure and cardiac output, each of which has a specific and independently
      variable hemodynamic cause. To assess whether analysis of the mitral and/or
      pulmonary venous flow-velocity patterns provides valuable information in the
      noninvasive assessment of the hemodynamic profile of CHF, these patterns were
      obtained by using the transthoracic approach in 18 patients with acute CHF with
      simultaneous measurements of catheter-derived mean pulmonary capillary wedge
      pressure and thermodilution cardiac index. Measurements were repeated on two
      occasions in each case: at the acute stage of CHF and 1 to 5 days after
      treatment. Peak diastolic pulmonary venous forward flow velocity was higher, the
      ratio of pulmonary venous systolic to diastolic peak forward flow velocity was
      lower, and the ratio of mitral early diastolic to late diastolic flow velocity
      was greater in patients with higher mean pulmonary capillary wedge pressure (r =
      0.80, n = 36, p < 0.01; r = -0.69, n = 36, p < 0.01; r = 0.71, n = 36, p < 0.01).
      Peak systolic pulmonary venous forward flow velocity and time-velocity integral
      of the systolic pulmonary venous flow wave were greater in patients with larger
      cardiac index (r = 0.80, n = 36, p < 0.01; r = 0.62, n = 36, p < 0.01). In
      conclusion, two primary sets of hemodynamic parameters, that is, left atrial
      pressure and cardiac output, can be estimated with Doppler pulmonary venous flow
      parameters in patients with acute CHF.

PMID- 7817904
TI  - Color flow Doppler determination of transmitral flow and orifice area in mitral
      stenosis: experimental evaluation of the proximal flow-convergence method.
AB  - To evaluate the in vivo accuracy of color Doppler flow-convergence methods for
      determining transmitral flow volumes and effective orifice areas in mitral
      stenosis, we studied two models for flow-convergence surface geometry, a
      hemispheric (HS) model and an oblate hemispheroid (OH) model in a chronic animal
      model with quantifiable mitral flows. Color Doppler flow mapping of the proximal
      flow-convergence region has been reported to be useful for evaluation of
      intracardiac flows. Flow-convergence methods in patients with mitral stenosis
      that use HS assumption for the isovelocity surface have resulted in
      underestimation of actual flows. Chronic mitral stenosis was created surgically
      in six sheep with annuloplasty rings (group 1) and 11 sheep with bioprosthetic
      porcine valves (group 2). Hemodynamic and echocardiographic/Doppler studies (n =
      18 in group 1; n = 21 in group 2) were performed 20 to 34 weeks later. Left
      ventricular inflow obstruction was of varied severity, with mean transmitral
      valve gradients in group 1 ranging from 1.3 to 18 mm Hg and in group 2 ranging
      from 6.3 to 25.6 mm Hg. Although transmitral flows derived by both geometric flow
      convergence models showed significant correlations with reference cardiac
      outputs, the correlations for the OH model were better than those for the HS
      model (group 1, r = 0.86 for the OH model vs r = 0.72 for the HS model; group 2;
      r = 0.84 for the OH model vs r = 0.62 for the HS model). The OH model was also
      superior to the HS model in determining effective orifice areas compared to
      reference orifice areas determined by postmortem planimetry of anatomic orifices
      (group 1 only, r = 0.64 for OH vs 0.58 for HS), by the Gorlin and Gorlin formula
      (group 1, r = 0.63 for OH vs 0.72 for HS; group 2, r = 0.82 for OH vs 0.76 for
      HS), and by the Doppler pressure half-time method (group 1, r = 0.76 for OH vs
      0.69 for HS; group 2, r = 0.84 for OH vs 0.62 for HS).(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7817905
TI  - Effect of acute pericardial tamponade on the relative contributions of systolic
      and diastolic pulmonary venous return: a transesophageal pulsed Doppler study.
AB  - The effect of acute pericardial tamponade on pulmonary venous return was assessed
      by transesophageal pulsed Doppler echocardiography. In 14 open-chest anesthetized
      dogs peak pulmonary venous flow velocities in systole (VJ) and in diastole (VK)
      were measured during apnea and atrial pacing while acute tamponade was induced by
      intrapericardial instillation of 0.9% sodium chloride solution. Before
      intravascular volume expansion, induction of acute tamponade resulted in a
      significant decline in VK (43 +/- 17 to 19 +/- 8 cm/sec; p < 0.05) but no change
      in VJ or the ratio VJ/VK. After intravascular volume expansion, induction of
      acute tamponade resulted in significant reductions in VJ (43 +/- 9 to 29 +/- 10
      cm/sec; p < 0.001) and VK (37 +/- 19 to 15 +/- 11 cm/sec; p < 0.001). The effect
      was disproportionately greater on VK, however, resulting in a significant
      increase in VJ/VK (1.51 +/- 0.84 to 2.58 +/- 1.41; p < 0.001). The
      disproportionate effect of acute tamponade on VK suggests that increased
      pericardial pressure directly constrains diastolic filling of the left atrium as
      a conduit to the left ventricle and that it does not decrease the systolic and
      diastolic phases of pulmonary venous return uniformly. Intravascular volume
      expansion increases cardiac output before acute tamponade, but during acute
      tamponade it amplifies the disproportionate impact of increased pericardial
      pressure on left ventricular diastolic filling as the left ventricle is
      constrained within the fluid-filled pericardial sac.

PMID- 7817906
TI  - Mechanism of balloon angioplasty in children with arterial stenosis assessed by
      intravascular ultrasound and angiography.
AB  - Fifteen patients were examined before and immediately after balloon angioplasty
      with a 4.3F, 30 MHz rotational tip intravascular ultrasound system. In 12 (80%)
      patients, 13 procedures could be analyzed because of sufficient image quality.
      The lesions for intravascular ultrasound (IVUS) study consisted of pulmonary
      arterial stenosis in 4 patients, Blalock-Taussig shunt stenosis in 3, coarctation
      of the aorta in 2, subclavian artery stenosis in 1, renal artery stenosis in 1,
      and ductus arteriosus in 1. Three distinctive morphologic types were identified:
      Group I had arterial stretching (3 patients); group IIa had superficial tearing
      (3); group IIb had deep intimal-medial tearing (5); group III had dissection (2).
      In the narrowest site, minimal and maximal luminal diameters, luminal area before
      and after balloon angioplasty were 3.5 +/- 1.8 mm vs 4.5 +/- 2.5 mm, 4.1 +/- 2.1
      mm vs 5.4 +/- 3.5 mm, and 49.8 +/- 30.2 mm vs 88.3 +/- 45.2 mm2, respectively.
      The recoil value of group IIb with appropriate balloon angioplasty was
      approximately 0.3. IVUS may be an useful modality for evaluating the morphologic
      mechanism of dilatation after balloon angioplasty.

PMID- 7817907
TI  - Effects of exercise on plasma level of brain natriuretic peptide in congestive
      heart failure with and without left ventricular dysfunction.
AB  - This study was designed to determine whether plasma brain natriuretic peptide
      (BNP) increases in response to exercise in patients with congestive heart failure
      and to show what kind of hemodynamic abnormalities induce increased secretion of
      BNP during exercise. Plasma levels of atrial natriuretic peptide (ANP) and BNP
      and hemodynamic parameters were measured during upright bicycle exercise tests in
      seven patients with dilated cardiomyopathy and nine with mitral stenosis. At
      rest, there were no intergroup differences in cardiac output or pulmonary
      capillary wedge pressure; however, the group with dilated cardiomyopathy had
      higher left ventricular end-diastolic pressures and lower left ventricular
      ejection fractions than did the group with mitral stenosis. Plasma ANP levels
      were comparable between the dilated cardiomyopathy group (170 +/- 77 [SE] pg/ml)
      and the mitral stenosis group (106 +/- 33 pg/ml) (p, not significant), whereas
      BNP was significantly higher in the dilated cardiomyopathy group (221 +/- 80
      pg/ml) than in the other group (37 +/- 10 pg/ml) (p < 0.05). The plasma
      concentration of BNP but not of ANP significantly correlated with left
      ventricular end-diastolic pressure and volume. Exercise increased plasma ANP and
      BNP in the two groups. The dilated cardiomyopathy group had a larger increment in
      BNP (+157 +/- 79 pg/ml) than did the mitral stenosis group (+17 +/- 5 pg/ml) (p <
      0.05), although the increase in pulmonary capillary wedge pressure was greater in
      the mitral stenosis group. Thus exercise increases plasma levels of BNP, and
      impaired left ventricular function may be a main factor in the greater increment
      in BNP during exercise in patients with congestive heart failure.

PMID- 7817908
TI  - The history of interventional cardiology: cardiac catheterization, angioplasty,
      and related interventions.
AB  - The histories of cardiac catheterization, angioplasty, and other catheter
      interventions are spectacular journeys marked by undeterred genius, serendipity,
      and the vindication of the scientific method. Cardiac catheterization began with
      Hales's 1711 equine biventricular catheterization, other early experimental
      catheterizations in the nineteenth century, and Forssmann's dramatic 1929 right
      heart self-catheterization. Cournand, Richards, and others finished unlocking the
      right heart in the 1940s; Zimmerman, Cope, Ross, and others unlocked the left
      heart in the 1950s; and the coronary arteries were inadvertently unlocked by
      Sones in 1958, leading to the advent of percutaneous femoral coronary angiography
      by Judkins and by Amplatz in 1967. Dotter's accidental catheter recanalization of
      a peripheral artery in 1963 ushered in the era of intervention, crowned by
      Gruentzig's balloon angioplasty in the mid-1970s and leading to today's panoply
      of devices used percutaneously to revascularize the coronary arteries in a
      variety of clinical settings.

PMID- 7817909
TI  - High-frequency ultrasound: determination of the lowest frequency required for
      cellular imaging and detection of myocardial disease.
AB  - We have previously demonstrated that a 600 MHz transducer enables the
      visualization of cellular detail in specimens of myocardium. However, lower
      frequency transducers are more practical and provide better tissue penetration
      for possible in vivo application of this technique. This study was designed to
      ascertain the lowest frequency at which cellular detail can be imaged. We
      performed ultrasound imaging of 5 microns sections of 14 samples of myocardium.
      Each specimen was examined serially with 600 MHz, 400 MHz, 200 MHz, and 100 MHz
      transducers. Normal cardiac myocytes and pathologic phenomena such as fibrosis,
      cell fallout, and round cell infiltration were clearly identified with a 600 MHz
      transducer. Although there was a slight decrease in resolution, normal and
      pathologic phenomena were also identified with 400 and 200 MHz transducers.
      However, cellular detail could not be adequately identified with a 100 MHz
      transducer. In conclusion, transducer frequencies of 600 to 200 MHz enable
      visualization of cell detail and detection of pathologic changes in the
      myocardium. A transducer frequency of at least 200 MHz is probably required for
      possible in vivo application of this technique.

PMID- 7817910
TI  - Selection criteria for placement of left ventricular assist devices.
AB  - The 2,000 heart donors available annually continue to be inadequate for the
      50,000 patients with end-stage congestive heart failure who require heart
      transplantation to survive. This discrepancy has led to the successful use of
      long-term implantable LVADs as a bridge to transplantation and has raised the
      issue of permanent device implantation in lieu of transplantation. The recent
      support by Food and Drug Administration medical advisory panel for widespread
      release of an implantable, long-term LVAD as a bridge to transplantation makes
      more widespread of the devices likely and mandates improved clinician awareness
      of the benefits and limitations of this new technology. We outline our
      indications and contraindications for insertion of implantable LVADs based on our
      4-year clinical experience with 29 patients.

PMID- 7817911
TI  - Intracoronary two-dimensional ultrasound imaging in the assessment of plaque
      morphologic features and the planning of coronary interventions.

PMID- 7817912
TI  - Hemodynamic evidence of painless myocardial ischemia with acute pulmonary edema
      in coronary disease.

PMID- 7817913
TI  - Papillary muscle rupture complicating inferior myocardial infarction:
      identification with transesophageal echocardiography.

PMID- 7817914
TI  - Transesophageal echocardiographically guided angiography of an anomalous coronary
      artery.

PMID- 7817915
TI  - Transvenous cardioverter-defibrillator implantation via persistent left superior
      vena cava.

PMID- 7817916
TI  - Efficacy and safety of metoprolol in the treatment of doxorubicin-induced
      cardiomyopathy in pediatric patients.

PMID- 7817917
TI  - Inherited restrictive cardiomyopathy in a 74-year-old woman: a case of Fabry's
      disease.

PMID- 7817918
TI  - Serial changes in left ventricular function after coronary artery bypass:
      implications in viability assessment.
AB  - Improvement in left ventricular (LV) performance after coronary artery bypass
      surgery remains the gold standard in myocardial viability assessment. The time
      related changes, however, are not well known. This study examined the LV ejection
      fraction (EF) by gated blood pool imaging early (6 +/- 4 days) and late (62 +/-
      24 days) after surgery in patients with normal preoperative EF (group 1, n = 12)
      and those with LV dysfunction (group 2, n = 15). There were no changes in the
      clinical status between the early and late studies, and all patients had normal
      sinus rhythm. Group 1 had no significant change in EF (preoperatively 62%, early
      postoperatively 64%, late postoperatively 63%; p = NS). In group 2, EF was 26% +/
      8% preoperatively; 30% +/- 10% early postoperatively; and 34% +/- 8% late
      postoperatively (p < 0.05). Postoperatively there was > or = 5% improvement in EF
      in 4 patients early and 11 patients late (p < 0.05). Patients who showed early
      improvement continued to do so in the late study but, additionally, 7 patients
      showed improvement only in the late study. Thus the timing of EF measurement
      after surgery is important in patients with LV dysfunction but not in patients
      with normal LV function. Early assessment may underestimate the prevalence and
      degree of recovery.

PMID- 7817919
TI  - Natural antioxidants and restenosis after percutaneous transluminal coronary
      angioplasty.

PMID- 7817920
TI  - Recovery of left ventricular function in acute nonischemic congestive
      cardiomyopathy.
AB  - The extent and time course of recovery of left ventricular function were
      investigated in 29 patients with no previous symptoms who had acute nonischemic
      congestive cardiomyopathy and left ventricular ejection fraction of 0.22 +/-
      0.07. Improvement in left ventricular ejection fraction by at least 0.05 was
      observed in 24 of the 29 patients and was achieved within 6 months after the
      initial evaluation. Progressive improvement was seen, with a maximum ejection
      fraction of 0.45 +/- 0.17 being achieved within approximately 18 months. The
      degree of ejection fraction recovery was not related to the initial clinical or
      hemodynamic variables. However, the extent of fibrosis detected on endomyocardial
      biopsy correlated inversely with subsequent changes in ejection fraction (r = 
      0.65, p = 0.0003). Thus significant recovery is likely after an acute episode of
      nonischemic cardiomyopathy and may be progressive during the first year. Recovery
      is related to the extent of myocardial fibrosis detected on endomyocardial biopsy
      but cannot be predicted from the initial clinical or hemodynamic presentation.

PMID- 7817921
TI  - Positive high-dose dipyridamole echocardiography test after acute myocardial
      infarction is an excellent predictor of cardiac events.
AB  - To determine the prognostic value of the high-dose (0.84 mg/kg over a 10-minute
      period) dipyridamole echocardiography test (DET) after a first acute myocardial
      infarction (AMI) in comparison with clinical, electrocardiographic,
      echocardiographic, and angiographic variables, follow-up data over an average
      period of 16 months were obtained in 93 consecutive patients. There were 41 total
      cardiac events (TCE): one death, two reinfarctions, 13 postinfarction anginas,
      five percutaneous transluminal coronary angioplasty procedures, and 20 coronary
      artery bypass graft procedures. TCE without revascularization procedures were
      considered adverse cardiac events (ACE). The DET result was positive in 28 of 41
      patients with TCE and in only 4 of 52 patients without TCE (p < 0.001). The
      sensitivity, specificity, and accuracy of positive DET in predicting TCE were
      68%, 92%, and 82%, respectively. According to Cox's proportional regression model
      the best predictor of TCE was positivity of DET (p = 0.002, relative risk ratio
      4.3), followed by multivessel coronary artery disease (p = 0.018, relative risk
      ratio 2.9) and patent infarct-related artery (p = 0.042, relative risk ratio
      2.9). DET was positive in 12 of 16 patients with ACE and 20 of 77 patients
      without ACE (p = 0.001). The sensitivity, specificity, and accuracy of DET in
      predicting ACE were 75%, 74%, and 74%, respectively. According to Cox's
      proportional regression model significant predictors of ACE were positivity of
      DET (p = 0.002, relative risk ratio 29.4) and ejection fraction < or = 40% at the
      time of DET (p = 0.017, relative risk ratio 22.2).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7817922
TI  - Protruding atheromas of the aortic arch in symptomatic patients with carotid
      artery disease.
AB  - Protruding aortic arch atheromas are associated with otherwise unexplained
      strokes and transient ischemic attacks. Therefore aortic atheromas also may be
      important in patients with carotid artery disease. Forty-five patients with > or
      = 50% carotid stenosis and stroke or transient ischemic attack within 6 weeks
      underwent transesophageal echocardiographic examination (TEE). They were matched
      for age, sex, and hypertension with 45 control subjects who had also had a recent
      cerebral event but in whom significant carotid stenosis was absent. Protruding
      aortic arch atheromas were present in 17 (38%) of 45 patients with carotid
      disease and only 7 (16%) of 45 of control subjects (p = 0.02). Mobile atheromas
      (with the greatest embolic potential) were present almost exclusively in case
      patients, 6 (13%) of 45, versus 1 (2%) of 45 control subjects (p = 0.05). Case
      patients with mobile atheromas had the most severe carotid stenosis ( > or =
      80%). Cerebral symptoms were discordant with the side of the carotid stenosis in
      10 case patients, and 4 had atheromas. In conclusion, protruding atheromas of the
      aortic arch are present in significant numbers of symptomatic patients with
      carotid artery disease. These atheromas may represent an additional cause of
      symptoms in patients with carotid stenosis. TEE to look for protruding aortic
      atheromas may be considered in patients with neurologic events despite the
      presence of significant carotid stenosis, especially if the symptoms are
      discordant with the side of carotid stenosis.

PMID- 7817923
TI  - Implantation of transvenous nonthoracotomy cardioverter-defibrillator systems in
      patients with permanent endocardial pacemakers.
AB  - Among 177 patients in whom a nonthoracotomy approach was initially used to
      implant a cardioverter-defibrillator system, 11 (6%) patients also received a
      separately implanted permanent pacemaker. The main problem encountered in these
      patients were previously implanted unipolar pacemakers (n = 3) and ventricular
      pacing leads positioned at the right ventricular apex, the latter interfering
      with optimal placement of the tripolar implantable cardioverter-defibrillator
      (ICD) lead (n = 9). The approaches used to solve these problems were
      individualized and included placement of the ICD sensing lead at the right
      ventricular outflow tract (n = 3), initial placement (n = 1) or subsequent
      repositioning (n = 2) of the right ventricular pacing lead at the outflow tract,
      upgrade from unipolar to bipolar systems (n = 2), reprogramming from the DDD to
      AAI mode (n = 2), inactivation of the pacemaker (n = 1), and simultaneous
      placement of a single-chamber atrial pacemaker with the ICD lead (n = 2). These
      revisions fulfilled the pacing needs in each patient and prevented unfavorable
      sensing interaction between the two systems.

PMID- 7817924
TI  - Effect of accessory pathway location on the efficiency of heating during
      radiofrequency catheter ablation.
AB  - During radiofrequency catheter ablation of accessory pathways there is a poor
      correlation between applied power and temperature at target sites for catheter
      ablation. This study was designed to examine the relation between power and
      temperature during radiofrequency catheter ablation in patients with accessory
      pathways and to identify the factors that affect the efficiency of heating,
      defined as the ratio of applied power and temperature. Twenty-nine patients
      underwent radiofrequency catheter ablation of an accessory pathway. Among 257
      energy applications, 108 were applied for ablation of a right-sided accessory
      pathway, 105 for a left-sided accessory pathway, and 44 for a posteroseptal
      accessory pathway. During each application of radiofrequency energy, temperature
      was continually monitored by use of an ablation catheter with a thermistor
      embedded in the tip of the distal electrode. During some applications of energy,
      fluctuations in temperature were observed. The average power, impedance,
      temperature, and efficiency of heating for all applications of radiofrequency
      energy was 37 +/- 11 W, 100 +/- 9 ohms, 53 +/- 9 degrees C, and 1.7 +/- 0.8
      degrees C/W (range 0.9 degrees to 6.6 degrees C/W), respectively. The efficiency
      of heating varied by location (p < 0.0001), with the greatest efficiency of
      heating for posteroseptal energy applications (2.3 +/- 1.2 degrees C/W, which
      were significantly greater than for left-sided (1.8 +/- 0.8 degrees C/W; p <
      0.01) or right-sided (1.2 +/- 0.4 degrees C/W; p < 0.0001) applications. Phasic
      fluctuation in temperature was observed during 127 (49%) energy applications, and
      the efficiency of heating was 1.5 +/- 0.7 degrees C/W.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7817925
TI  - Diurnal variation of ventricular response to atrial fibrillation in patients with
      advanced heart failure.
AB  - Variability of ventricular rate was quantified by two measures of heart rate
      variability: the SD of the mean R-R interval (SDNN) and the SD of the 5-minute
      mean R-R interval (SDANN). In 35 patients with atrial fibrillation and advanced
      heart failure (left ventricular ejection fraction 20% +/- 9%, cardiac index 2.4
      +/- 0.7 L/min/m2), SDNN and SDANN were compared to 13 preselected clinical and
      hemodynamic variables for prediction of outcome. During a 12-month follow-up
      period, 8 (23%) patients deteriorated clinically; 3 (9%) died, and 5 (14%)
      underwent heart transplantation. SDNN and SDANN correlated to the difference of
      the mean R-R interval between night (2 AM to 3 PM) and day (11 AM to noon) with r
      values of 0.62 and 0.77, respectively. From 15 preselected variables, only SDANN
      (chi 2 = 6.7, p = 0.01) was independently associated with survival on
      multivariate analysis. Dichotomized SDANN at 100 msec accurately predicted 12
      month survival in 28 (80%) patients (relative risk = 9.77, p = 0.001). In
      conclusion, analysis of heart rate variability is useful in quantifying diurnal
      variation of ventricular rate in atrial fibrillation and might be useful in
      predicting survival in patients with advanced heart failure.

PMID- 7817926
TI  - Resolution of left atrial spontaneous echocardiographic contrast after
      percutaneous mitral valvuloplasty: implications for thromboembolic risk.
AB  - Left atrial spontaneous echocardiographic contrast (SEC) is an important marker
      of increased thromboembolic risk in patients with mitral stenosis. To evaluate
      the effect of percutaneous transseptal mitral valvuloplasty (PTMV) on SEC, we
      performed transesophageal echocardiography 1 day before and 3 months after PTMV
      on 88 consecutive patients. SEC was present in 65 (74%) patients before PTMV and
      was associated with absence of moderate or severe mitral regurgitation (p =
      0.01), a smaller valve area (p = 0.02), an older age (p = 0.04), and atrial
      fibrillation (p = 0.05). At 3 months, PTMV resulted in a mean absolute and
      relative increase in valve area of 0.54 +/- 0.36 cm2 and 53% +/- 43%,
      respectively. SEC resolved in 37 patients but persisted in 28 (32%) patients at
      the 3-month study. The absolute and relative increase of valve area and worsened
      mitral regurgitation after PTMV were predictors of resolution of SEC, with the
      relative increase in valve area being the only significant predictor on
      multivariate analysis. PTMV frequently results in resolution of SEC, which may
      have important implications in reducing the thromboembolic risk in these
      patients.

PMID- 7817927
TI  - Segmental analysis of resting echocardiographic function and stress scintigraphic
      perfusion: implications for myocardial viability.
AB  - In 73 patients with coronary artery disease, we performed segmental analysis of
      resting two-dimensional echocardiography and stress thallium-201 single photon
      emission computed tomographic scintigraphy with 24-hour delayed imaging to test
      the hypotheses that (1) combined analysis of stress thallium-201 scintigraphy
      (with 24-hour redistribution) and echocardiography provides an evaluation of the
      viability of most myocardial segments; and (2) the severity of the scintigraphic
      perfusion abnormality in a given segment is equivalent to the severity of its
      echocardiographically determined functional impairment. Scintigraphy showed 14%
      of the 1168 segments analyzed to have fixed severe defects. Echocardiography
      showed 11% of the 1070 segments analyzed to be akinetic or dyskinetic. However,
      with combined analysis, only 62 (5%) segments showed no evidence of viability by
      either imaging technique. We conclude that in this group of patients, 95% of
      segments have evidence of viability by one of these two conventional imaging
      techniques.

PMID- 7817928
TI  - Limitations of transesophageal echocardiography in the risk assessment of
      patients before nonanticoagulated cardioversion from atrial fibrillation and
      flutter: an analysis of pooled trials.
AB  - Recent studies have proposed that the exclusion of an atrial thrombus by
      transesophageal echocardiography (TEE) would allow for the safe cardioversion
      from atrial fibrillation or flutter without the need of prophylactic
      anticoagulation. Because all of the TEE trials have been small and descriptive
      and have lacked randomized, conventionally treated control groups, the pooled
      risk of embolic events from TEE trials was compared with that of a control group
      pooled from the literature on cardioversion both with and without conventional
      anticoagulation. Studies were identified from a MEDLINE search, references in
      review articles, and recent cardiology abstracts and were included if there were
      > 10 patients and if atrial fibrillation or flutter was of > 48 hours' duration.
      Where > 1 study had been published by the same group only the largest study was
      used. Studies were not selected by cause of arrhythmia, by predisposing risk
      factors for atrial fibrillation and flutter, or by method of cardioversion. The
      only patients excluded from TEE reports were those with atrial thrombi diagnosed
      on the precardioversion TEE or those documented to have adequate standard
      precardioversion anticoagulation. Seven TEE and 18 control studies met the
      inclusion criteria. More patients in the control studies had rheumatic valvular
      disease. Embolic events were significantly more frequent in the TEE group than in
      the anticoagulated control group (1.34% vs 0.33%, respectively; p = 0.04),
      whereas there was no significant difference between the TEE group and the
      nonanticoagulated control group (2.00%; p = 0.26). Thus the use of TEE screening
      to exclude patients with atrial thrombi before cardioversion does not identify
      patients who can safely undergo this procedure without anticoagulation.

PMID- 7817929
TI  - Echocardiographic predictors of success of catheter closure of atrial septal
      defect with the buttoned device.
AB  - Transcatheter occlusion of ostium secundum atrial septal defects (ASD) with the
      buttoned device has been shown to be feasible, effective, and safe. The final
      decision to implant the device is largely based on the balloon sizing of the ASD
      during cardiac catheterization. Only subjective criteria of ASD size and the
      septal rims on echocardiography have been used before catheterization, balloon
      sizing, and transcatheter occlusion. The purpose of this study was to determine
      whether objective echo criteria could be developed to predict successful
      occlusion of the ASD. During a 46-month period ending August 1992, 29 children
      with secundum ASD were evaluated for transcatheter occlusion. The device was
      successfully implanted in 15 (group A); in the remaining 14 children, this
      procedure could not be performed (group B). Preocclusion echos were analyzed by
      independent investigators who had no knowledge of outcome of the procedure. Echo
      parameters studied included size of ASD, length of atrial septum (LAS), and size
      of the superior and inferior rims in precordial and subcostal views and maximum
      jet width by color flow mapping. From these measurements several ratios were
      derived, and the data were compared. A smaller (p < 0.05) ASD was present in the
      group of patients with successful implantation of the device; LAS was similar (p
      > 0.1) in both groups. A lower (p < 0.05) ratio of ASD to LAS and a higher (p <
      0.05) ratio of the superior and inferior septal rims to ASD were associated with
      the group of patients with successful implantation of the device.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7817930
TI  - Gender differences in dehydration-induced mitral valve prolapse.
AB  - Mitral valve prolapse (MVP) is a common cardiac valve abnormality that affects
      women more frequently than men. We have previously shown that mild dehydration
      induces echocardiographic signs of MVP in approximately 50% of healthy asthenic
      women with previously normal cardiac findings. The present study was designed to
      investigate whether dehydration can induce MVP in normal men. Ten healthy male
      volunteers with a mean body mass index of 24.2 kg/m2, unremarkable history, and
      normal cardiac findings and echocardiogram were examined after mild diuresis with
      20 mg furosemide. Significant decrease in weight, left ventricular end-diastolic
      dimension, and cardiac output were detected in all subjects after furosemide
      administration. In 1 (10%) of the 10 subjects echocardiographic MVP developed
      after furosemide administration. All furosemide-induced changes resolved with
      hydration. These results demonstrate that dehydration-induced MVP in men without
      characteristic body habitus of MVP occurs with substantially lower frequency than
      previously documented in women with the characteristic body habitus of MVP. This
      study suggests the importance of gender and body habitus in dehydration-induced
      MVP.

PMID- 7817931
TI  - Multicenter trial of sotalol compared with procainamide in the suppression of
      inducible ventricular tachycardia: a double-blind, randomized parallel
      evaluation. Sotalol Multicenter Study Group.
AB  - Sotalol is the prototype class III agent that combines beta-blocking properties
      with the propensity to prolong the effective refractory period by lengthening the
      action potential duration. Its precise effect on the prevention of ventricular
      tachycardia-ventricular fibrillation (VTVF) compared to class I agents has not
      been evaluated in a blinded study. In a double-blind parallel-design multicenter
      study, the electrophysiologic and antiarrhythmic effects of intravenous and oral
      sotalol (n = 55) and procainamide (n = 55) were therefore compared in patients
      with VTVF inducible by programmed electric stimulation. Sotalol produced a
      greater effect on lengthening the ventricular effective refractory period (VERP).
      It prevented the inducibility of VTVF in 30% versus 20% for procainamide, but
      this was not significantly different. In an alternate therapy group (n = 41) of
      similar patients previously refractory to or intolerant of procainamide,
      intravenous sotalol prevented inducibility in 32%. The pooled overall sotalol
      efficacy rate was 31%. There was a significant relation between the increase in
      the VERP and the prevention of inducibility of VTVF (n = 56; p < 0.02). VERP of >
      or = 300 msec was critical for the prevention of VTVF inducibility. Thirteen
      sotalol and 6 procainamide responders from the randomized group and 30 from the
      nonrandomized groups completed 1 year of oral sotalol therapy follow-up. Life
      table analysis of these patient in each group showed a trend in favor of sotalol;
      however, statistical analysis was not possible because of the small numbers of
      patients. Both sotalol and procainamide were well tolerated. In the randomized
      group there was one case of sudden death during treatment with sotalol and two
      cases of nonfatal torsades de pointes in the procainamide group and two in the
      sotalol group; in the nonrandomized alternate therapy group, there were 6 cases
      of nonfatal torsades de pointes. The data support the emerging role of sotalol in
      the control of symptomatic ventricular tachycardia and fibrillation.

PMID- 7817933
TI  - A surgical pathologist views practice parameters.

PMID- 7817932
TI  - Lymphocyte G proteins reflect response to treatment in congestive heart failure.
AB  - Congestive heart failure is associated with chronotropic and inotropic
      hyporesponsiveness to adrenergic stimulation. A decrease in Gs alpha or an
      increase in Gi alpha is associated with a decrease in adenylyl cyclase activity.
      The current study assessed G proteins in response to treatment with direct-acting
      vasodilators and correlated changes in lymphocyte beta-adrenergic receptor
      components with changes in hemodynamic variables. Twenty-three patients with
      severe chronic congestive heart failure (New York Heart Association functional
      classes III and IV) were studied. Patients were grouped as responders (n = 10) or
      nonresponders (n = 13) on the basis of clinical assessment of functional status
      from questionnaires. Therapy was associated with an increase in cardiac index, a
      decrease in mean arterial pressure, and a decrease in systemic vascular
      resistance in all patients. Left ventricular filling pressure significantly
      decreased in responders (26 +/- 2 mm to 13 +/- 3 mm, p < 0.05) but did not change
      significantly in nonresponders. Similarly, mean right atrial pressure
      significantly decreased in responders (11 +/- 2 mm Hg to 4 +/- 1 mm Hg, p < 0.05)
      but did not change in nonresponders. Plasma norepinephrine increased
      significantly only in nonresponders (679 +/- 100 pg/ml to 1233 +/- 201 pg/ml, p <
      0.05). Whereas lymphocyte beta-adrenergic receptor density and Gs did not
      significantly change, Gi increased after treatment only in the nonresponder group
      (23 +/- 5 to 51 +/- 11 fmol/mg, p < 0.05). A poor response to direct-acting
      vasodilators can be distinguished by reactive increases in plasma norepinephrine
      and lymphocyte Gi in the absence of a decrease in either left- or right-sided
      filling pressures.

PMID- 7817934
TI  - EDTA-dependent pseudothrombocytopenia. Association with antiplatelet and
      antiphospholipid antibodies.
AB  - In a study of 88 patients with EDTA-dependent pseudothrombocytopenia (PTCP), EDTA
      dependent antiplatelet antibodies were seen in the sera of 72 (81.8%) patients
      (44 IgM, 25 IgG, and 3 IgA). The same sera also were tested for anticardiolipin
      antibodies (aCL), and 56 (63.6%) patients had sera that also were reactive for
      aCL (33 IgM, 21 IgG, and 2 IgA). The 16 patients who were negative for
      antiplatelet antibodies also were negative for aCL antibody. Overall concordance
      between antiplatelet and aCL antibodies was 82.9%; the correlation between
      antiplatelet and aCL antibody isotype distribution was 82.1%. Following
      cardiolipin absorption, most of the PTCP-sera were negative for antiplatelet
      activity, and no longer reproduced platelet clumping when incubated with normal
      blood. This finding showed that the antiplatelet antibodies cross-reacted with
      negatively charged phospholipids. However, after absorption on normal platelets,
      complete inhibition of aCL activity was observed in 34 (60.7%), and partial
      inhibition in 14 of the 56 patients who were aCL positive. These findings support
      the hypothesis that antibody subpopulations (naturally occurring autoantibodies)
      directed against negatively charged phospholipids can bind to antigens modified
      by EDTA on the platelet membrane, and may be responsible for PTCP genesis.

PMID- 7817935
TI  - An evaluation of two commercial test procedures for the detection of lupus
      anticoagulant.
AB  - The authors have evaluated two commercial assays for lupus anticoagulants (LA),
      the DVVtest+DVV confirm (American Diagnostica, Greenwich, CT) and the PTT
      LA+Staclot LA (Diagnostica Stago, Asnieres-Sur-Seine, France). The assays were
      compared with a previously described quantitative, semi-automated, and computer
      assisted test, which is based on two assays, using the activated partial
      thromboplastin time (APTT) and the Russell's viper venom time (RVVT),
      respectively. Thirty well-characterized LA-positive and 30 LA-negative plasma
      samples were used to test the commercial assays. In some samples, both commercial
      tests failed to detect weak or moderately strong LAs. The sensitivity was 80% for
      the DVVtest+DVV confirm and 67% for the PTT-LA+Staclot LA. However, by applying
      both the two commercial tests to all plasma samples, 29 of 30 LA-positive plasma
      samples were diagnosed (sensitivity 97%). No false positive test results were
      found (specificity 100%).

PMID- 7817936
TI  - DNA and PCNA content of renal cell carcinoma and prognosis.
AB  - Robson stage I or II renal carcinomas have a heterogenous clinical outcome. A
      variety of morphologic features and other parameters have been proposed as
      prognostically useful. The authors measured the DNA content and PCNA expression
      of 47 stage I or II renal carcinomas, and assessed the association of these
      measures with pathologic stage, nuclear grade, and clinical course. Approximately
      56% of stage I neoplasms and 40% of stage II neoplasms were diploid. Five of 9
      neoplasms in which multiple samples were analyzed manifested both aneuploid and
      diploid regions. PCNA expression was noted in 20 of 32 stage I neoplasms and 9 of
      15 stage II neoplasms, and varied greatly among the neoplasms. Neither ploidy nor
      PCNA expression is associated with clinical behavior in these data. These results
      are different from some of those previously reported by others. These
      discrepancies are likely to be due to differences in methodology and the fact
      that there were only eight cases of metastatic disease. No single parameter will
      serve as a completely accurate prognostic indicator. Most individuals with these
      neoplasms will do well because all of the tumor has been excised.

PMID- 7817937
TI  - Cytogenetic and immunohistochemical profile of myxoid liposarcoma.
AB  - Cytogenetic and immunohistochemical studies were performed in nine myxoid
      liposarcomas. The tumor karyotype was determined after short-term culture of
      cells in vitro. Immunohistochemical studies were performed on frozen tissue in
      five cases and on paraffin-embedded tissue in three cases. Chromosomal analysis
      demonstrated a balanced translocation t(12;16) (q13;p11) as the sole abnormality
      in four cases. Two cases showed an association with other abnormalities. Three
      tumors showed variants of the t(12;16) translocation involving other chromosomes.
      In all cases studied, the 12q13 breakpoint was involved in rearrangements. In the
      majority of cases, immunohistochemical studies demonstrated vimentin (9 of 9) and
      S-100 protein (8 of 9). Strong focal expression of desmin was observed in two
      tumors. Weak focal expression was observed in three tumors. Two tumors, which
      were both desmin positive, showed focal expression of MSA and alpha-SMA. Strong
      expression of CD36 was present in all four cases that were studied for this
      marker. CD34 was negative in tumor cells, but it highlighted an intricate
      capillary network in the tumor. Close relationship between the tumor cells and
      pericapillary pericytes was demonstrated with CD34 and alpha-SMA strains. The
      authors conclude that myxoid liposarcoma is characterized by a specific
      chromosomal rearrangement. Its immunohistochemical profile is wider than
      previously believed, including expression of muscle markers.

PMID- 7817938
TI  - Histiocytic reaction in pelvic peritoneum associated with oxidized regenerated
      cellulose.
AB  - The authors present five cases of an unusual inflammatory reaction in pelvic
      peritoneal tissues associated with oxidized regenerated cellulose, a topical
      hemostatic agent. The findings were observed in specimens from five women who had
      been treated with oxidized regenerated cellulose during abdominal surgery.
      Histologically, the lesion was characterized by collections of large cells
      beneath the mesothelial surface, with small bland nuclei and abundant granular
      basophilic cytoplasm that stained bright red with mucicarmine.
      Immunohistochemical studies demonstrated that these cells stained positive for
      KP1 (CD68) confirming their histiocytic nature, and negative for cytokeratin and
      S-100 protein excluding the diagnoses of carcinoma and granular cell tumor
      respectively. Although unlikely, the mucicarmine positivity may be
      misinterpreted, leading to a erroneous diagnosis of adenocarcinoma. To avoid
      misdiagnosis, pathologists need to be aware of this lesion.

PMID- 7817939
TI  - Pathology is more than just microscopy.

PMID- 7817940
TI  - Cytologic/histologic correlation for quality control in cervicovaginal cytology.
      Experience with 1,582 paired cases.
AB  - For quality-control purposes, federal regulations require cytology laboratories
      to compare Papanicolaou smear and cervical biopsy reports, if available, and
      determine the cause of any discrepancies. The authors reviewed 56,497
      cervicovaginal smears, of which 1,582 (2.8%) had a subsequent cervical biopsy or
      endocervical curettage within 2 months. A total of 175 discrepancies (11%) were
      identifed, and biopsies and smears from these cases were reviewed at a weekly
      conference. In the majority of cases, the diagnosis of the smear and biopsy was
      confirmed on review, and the discrepancy was attributed to sampling error (n =
      159; 91%). Six cases (3.4% of all discrepant cases) were errors in cytologic
      diagnosis. Five of these were interpretation errors, and one case was a screening
      error. There were 10 errors in the evaluation of cervical biopsies (5.7% of all
      discrepant cases): five biopsies were undercalled, and five were overdiagnosed as
      a squamous intraepithelial lesion. The results of testing for human
      papillomavirus DNA by in situ hybridization were helpful in arbitrating some
      diagnositic disagreements.

PMID- 7817941
TI  - Fine-needle aspiration cytologic diagnosis of lymphoepithelioma-like carcinoma of
      the lung. Report of two cases with immunohistochemical study.
AB  - Lymphoepithelioma is a term used to describe an undifferentiated carcinoma with
      prominent lymphoid infiltration in the nasopharynx. Recently, tumors with similar
      histology, designated as lymphoepithelioma-like carcinomas, have been described
      in other sites including the lung. The authors report two cases of pulmonary
      lymphoepithelioma-like carcinoma that were correctly diagnosed by fine-needle
      aspiration cytology. The distinctive cytologic features consist of cohesive
      sheets and clusters of spindle tumor cells, which possess moderately pleomorphic
      vesicular nuclei and prominent nucleoli that are intimately intermixed with
      numerous small lymphocytes. Immunohistochemical study, performed on the cell
      block preparation, revealed strong positive staining of these tumor cells for
      epithelial markers. In both cases, the cytologic diagnosis were confirmed
      subsequently by histologic examination of the resected surgical specimens.
      Cytologically, the differential diagnoses include granulomatous inflammatory
      diseases (especially tuberculosis), malignant lymphoma, melanoma, and metastatic
      sarcoma. The characteristic cytology of the tumor cells, together with their
      pattern of immunohistochemical staining, are helpful to distinguish
      lymphoepithelioma-like carcinoma from the differential diagnoses. In these cases,
      careful examination of the nasopharynx, preferably with multiple random mucosal
      biopsies, is essential for the exclusion of nasopharyngeal undifferentiated
      carcinoma because of the obvious differences in treatment and prognosis.

PMID- 7817942
TI  - T-cell-rich B-cell lymphoma. Reflections on changes in hematopathology.

PMID- 7817943
TI  - Differentiation and risk assessment of gastrointestinal stromal tumors.
AB  - Predicting prognosis and identifying the line of differentiation in
      gastrointestinal stromal tumors (GIST) have been problematic. The first part of
      this review briefly summarizes ultrastructural studies and then focuses on the
      many immunohistochemical studies of cellular differentiation in GIST. The second
      part reviews pathologic evaluation of GIST from the perspective of risk
      assessment. A scheme is proposed for segregating GIST into groups with low and
      high risk for aggressive clinical behavior.

PMID- 7817944
TI  - Rapid method for detection of Aspergillus 5S ribosomal RNA using a genus-specific
      oligonucleotide probe.
AB  - Ribosomal RNA (rRNA) is present in all prokaryotic and eukaryotic cells. Although
      sequences are conserved, variations in nucleic acid composition are known to be
      species specific. Formalin or Bouin's fixed, paraffin-embedded tissue specimens
      from 17 cases of culture proven Aspergillus sp infections were studied by a rapid
      (< 30 minutes) in situ hybridization procedure using a biotinylated
      oligonucleotide DNA probe complementary to nucleic acids 1-22 of Aspergillus sp
      5S rRNA sequence. Positivity was noted within fungal organisms in all 17 cases
      and was identified in both hyphal forms and within fruiting bodies. Signal was
      weak or absent within the center of Aspergillus abscess cavities with increasing
      signal located toward the periphery of the cavity, suggesting that rRNA in situ
      hybridization may detect viable fungal forms. In situ hybridization with the
      oligonucleotide probe on tissues containing several different organisms including
      Candida sp, Histoplasma capsulatum, Cryptococcus neoformans, Pneumocystis
      carinii, Pseudallescheria boydii, Fusarium sp, and Mucor were negative. Use of
      site specific oligonucleotide probes specific for a variety of rRNA sequences may
      aid in the diagnosis of several medically important bacterial, fungal, and
      protozoal pathogens.

PMID- 7817945
TI  - Laboratory detection of Clostridium difficile. A comparison of media and
      incubation systems.
AB  - Parallel testing for culture recovery of Clostridium difficile was performed
      using three selective media in each of four anaerobic incubation environmental
      systems. Testing was completed on 67 stool samples from 60 hospitalized patients
      in whom C difficile-associated diarrhea was suspected. Three different media were
      evaluated: CCFA (modified cycloserine-cefoxitin-fructose agar), CCFA-PRAS (CCFA,
      prereduced-anaerobically-sterilized) and CMBA (modified cycloserine-mannitol
      blood agar). The incubation systems compared were an anaerobic chamber (Model 800
      Anaerobic Environmental System, Anaerobe Systems, San Jose, CA), the anaerobic
      jar (BBL, Cockeysville, MD), the anaerobic Bio-Bag (BBL), and the anaerobic pouch
      (BBL). C difficile was found in 16 samples collected from 15 patients. Comparing
      recovery on the various types of media in all four anaerobic atmospheres, C
      difficile was recovered on all (64) CCFA plates, 56 of 64 CCFA-PRAS plates, and
      43 of 64 CMBA plates (P < .03 comparing CCFA and CMBA). Of the 48 plates in each
      incubation system that were inoculated with specimens positive for C difficile,
      the organism was recovered from 43 plates in the anaerobe chamber, 41 incubated
      in an anaerobe jar, 40 in the Bio-Bag, and 39 incubated in the GasPak pouch, all
      providing similar recovery of C difficile (P = .08). The CCFA-PRAS and CMBA media
      demonstrated less inhibition of normal stool flora compared to the CCFA. Overall
      CCFA that was anaerobically reduced at least 4 hours before use, and contained
      the original concentration of antimicrobial agents described by George and
      colleagues, was superior to CMBA for recovery of C. difficile.

PMID- 7817946
TI  - A molecular-based magnet test for malaria.
AB  - The molecular-based magnet test for malaria is shown to be more sensitive than
      the thin blood film test. The globally used thin blood film test is less
      sensitive because it uses preparation steps that result in the reduction of the
      absolute number of diagnostically pertinent erythrocytes. Several reports of
      diagnostic error with the thin film test and the thick film test have appeared in
      the literature. In marked contrast to the commonly accepted tests, the magnet
      test concurrently partitions and concentrates the infected erythrocytes present
      in the initial sample. The magnetic test permits a brief and sensitive
      microscopic-based enumeration of the malaria-infected erythrocytes in the
      enriched sample. Diagnostically pertinent hemozoin is simply identified through
      two of its specific molecular properties: paramagnetism and birefringence. The
      former property mediates the capture and enrichment of malaria-infected
      erythrocytes within the magnetic flux and the latter property manifests the
      characteristic birefringence demonstrated by polarized light.

PMID- 7817947
TI  - Frozen section examination of breast biopsies. Practice parameter.
AB  - Traditionally, if the clinical diagnosis is cancer, fresh breast tissue is
      submitted for frozen section examination before immediate mastectomy. Although
      this is still true, many breast biopsies are currently performed as outpatient
      procedures in the setting of an abnormal mammogram or a vaguely palpable
      abnormality. Frequently the lesion is small (less than 1.0 cm.) or is not grossly
      visible. The appropriate pathologic examination of breast biopsy material is
      determined by whether it is a mass or only a cluster of calcifications seen on a
      mammogram. Each breast biopsy specimen must be handled in a manner that will
      maximize the opportunity to arrive at the correct histologic diagnosis. In many
      instances, this means that a frozen section examination is contraindicated.

PMID- 7817948
TI  - T-cell-rich B-cell lymphoma. A clinicopathologic study of eight cases.
AB  - Although T-cell-rich B-cell lymphoma (TCRBCL) is a recently recognized form of
      non-Hodgkin's lymphoma (NHL), limited information regarding its incidence,
      cellular origin, morphologic spectrum, and biologic behavior is currently
      available. In this study, the clinicopathologic features of eight patients with
      TCRBCL are presented. This neoplasm comprised about 1% of all NHLs seen at Emory
      University Hospital over 2 years. The male-to-female ratio was 1.6, and the mean
      age at diagnosis was 60 years. At presentation, TCRBCL was nodal in 88% of the
      patients and widely disseminated in 50% of the patients. A complete remission was
      seen in three of the five patients treated with combination chemotherapy that was
      directed at intermediate grade NHL. Three patients received inadequate or
      incomplete chemotherapy. One of these patients later achieved a complete
      remission with more intensive therapy. Two of the patients were not evaluable for
      response to therapy. The actuarial and disease-free survival rates of the group
      at 5 years were 72% and 21%, respectively. Morphologically, the lymph nodes in
      seven of eight cases were diffusely obliterated, whereas one had markedly
      expanded interfollicular zones that lead to an initial diagnosis of T-zone
      lymphoma. All tumors were characterized by no more than 25% large lymphoid cells,
      which were scattered in a background of small lymphocytes with round or irregular
      nuclei. The presence of numerous histiocytes imparted a lymphoepithelioid
      appearance in two cases. Although immunoperoxidase stains of frozen tissue were
      initially suggestive of a peripheral T-cell lymphoma in some cases, paraffin
      immunoperoxidase stains clearly established the B-cell nature of the large cells,
      whereas most of the small cells were T lymphocytes. The clonal nature of the
      large cells was confirmed in seven cases by monotypic immunoglobulin (Ig) light
      chain restriction or Ig gene rearrangements. Epstein-Barr virus genomic DNA was
      detected in two of the six cases tested by polymerase chain reaction or Southern
      blot analysis, but no evidence of a bcl-2 rearrangement was found in any of the
      five cases examined. These findings indicate that TCRBCL is an uncommon form of
      NHL with a therapeutic response and overall survival consistent with intermediate
      grade lymphoma. Paraffin immunoperoxidase stains and occasionally genotypic
      analysis are required to exclude the diagnosis of PTCL or diffuse lymphocyte
      predominant Hodgkin's disease. The authors found no morphologic or molecular
      evidence to support a follicular center cell origin in these cases of TCRBCL.

PMID- 7817949
TI  - Large granular lymphocyte leukemia. A study of nine cases in a Chinese
      population.
AB  - Large granular lymphocyte (LGL) leukemia is a neoplastic disorder of lymphocytes
      that is characterized by the presence of prominent cytoplasmic granules, and
      involves the proliferation of at least two distinct cell types, T cells and
      natural killer (NK) cells. The authors report the clinical and pathologic
      features of 9 Chinese patients with LGL leukemia, who represented 14% of 64 cases
      of chronic lymphoproliferative disorders diagnosed at their centers in 3 years.
      Three different groups could be defined on immunophenotypic and clinical grounds.
      The first group of 4 cases were CD2+CD3+CD4-CD8+. With the exception of a
      pediatric case, these cases ran an indolent course that was similar to the T-cell
      LGL leukemia most common in Western patients. However, thrombocytopenia and pure
      red cell aplasia were more common in the patients in this study, which was
      similar to the experience in Japanese patients. The second group of two cases
      were CD2+CD3+CD4+CD8-, and appeared to have worse outcomes than the first group.
      The third group of 3 cases were CD2+CD3-CD4-CD8-CD56+. Although phenotypically
      similar to the NK-cell LGL leukemia reported in Western patients, these cases
      were clinically more aggressive than their Western counterparts. This study is
      the first to report comprehensively the different types of LGL leukemias in
      Chinese patients, and provides useful information on the similarities and
      similarities and differences of these disorders as compared to those cases in the
      West.

PMID- 7817950
TI  - Comparison of two methods of mechanical disaggregation of scirrhous breast
      adenocarcinomas for DNA flow cytometric analysis of whole cells.
AB  - Mechanical release of single cell suspensions from solid tumors for DNA analysis
      by flow cytometry has been shown to be optimal for adenocarcinomas in general. In
      the breast, many adenocarcinomas are fibrotic or scirrhous, creating difficulty
      in separating the neoplastic cells from the stroma. The authors have conducted a
      parallel study in 20 consecutive cases of scirrhous adenocarcinomas of the breast
      using two mechanical methods of cell disaggregation by: (1) mincing tumor tissue
      in culture media (MINCE); and (2) scraping the surface of the solid tumor with a
      scalpel blade and rinsing the blade in culture media (SCRAPE). Both methods were
      compared with PI staining and quantitation of percent debris and coefficient of
      variation (CV), as an index of resolution of the G0/G1 tumor peak. Debris was
      quantitated using Cell-FIT (Becton Dickinson Immunocytometry Systems, San Jose,
      CA) and Multicycle (Phoenix Flow Systems, San Diego, CA) software programs. With
      Multicycle, in addition to debris and aggregate determination, an index that
      included background, aggregates and debris (%BAD) occurring between the
      boundaries of the tumor G1 and G2 region was evaluated. In the 4 DNA diploid and
      16 DNA aneuploid tumors, there was no significant difference in histogram quality
      measured by CV or amount of debris, aggregates, and %BAD between MINCE and SCRAPE
      methods. The authors conclude that either method of mechanical disaggregation
      will produce DNA histograms of comparable quality and degree of resolution.
      However, the scrape method may be advantageous in the mechanical disaggregation
      in scirrhous tumors. The scrape method also may be useful in small tumors, where
      tissue preservation for histology is paramount, and there is insufficient
      material to separately submit for flow cytometry. Combination of both MINCE and
      SCRAPE may provide higher cell yields, than using only one of these dissociation
      techniques. In addition, DNA analysis methods using intact cells obtained with
      the SCRAPE method result in percent CV values of similar resolution to those
      reported for methods producing bare nuclear suspensions from fresh tumors.

PMID- 7817952
TI  - Extranodal follicular dendritic cell sarcoma of the gastrointestinal tract.
      Morphologic, immunohistochemical and ultrastructural analysis of two cases.
AB  - Tumors showing differentiation toward follicular dendritic cells are rare and
      usually occur in lymph nodes. Their occurrence at extranodal sites was recognized
      recently. This report documents two further extranodal cases, one arising in the
      small intestine of a 23-year-old woman and the second in periduodenal
      retroperitoneal soft tissue of a 63-year-old man. Both neoplasms displayed a
      typical biphasic morphologic pattern, composed of large cells with indistinct
      cytoplasmic borders creating a syncytial appearance, admixed with spindle cell
      areas resembling malignant fibrous histiocytoma, and infiltrated by numerous
      small T lymphocytes. Expression of CD21 and CD35, together with ultrastructural
      demonstration (in one case) of long cytoplasmic processes connected by
      desmosomes, confirmed follicular dendritic cell differentiation. One case also
      expressed HLA-DR, and both showed aberrant epithelial membrane antigen staining.
      Neither tumor showed CD45 expression. In both cases the tumors were treated by
      local excision. Case 1 has shown an unusually aggressive course with extensive
      intraperitoneal recurrence. The biphasic morphologic pattern and tumor
      immunophenotype are discussed in relation to increasing evidence of
      immunophenotypic and morphologic heterogeneity of normal follicular dendritic
      cells.

PMID- 7817951
TI  - Bone marrow involvement in anaplastic large cell lymphoma. Immunohistochemical
      detection of minimal disease and its prognostic significance.
AB  - Bone marrow involvement by anaplastic large cell anaplastic large cell (ALC)
      lymphoma can be difficult to detect on routine morphologic examination alone. In
      a series of 42 patients with ALC lymphoma, the authors analyzed: (1) the
      usefulness of a limited panel of monoclonal antibodies directed against CD30 (Ber
      H2, HRS4) and epithelial marrow involvement on routinely processed biopsy
      specimens; and (2) the prognostic significance of bone marrow involvement as
      detected on both morphologic and immunohistochemical grounds. On conventional
      examination, 17% of the patients were found to have bone marrow involvement at
      diagnosis. However, after immunohistochemical analysis, occult malignant cells
      were detected in 23% of the patients with negative bone marrow biopsy on routine
      histology. The low percentage of positive cases on routine morphologic
      examination compared to immunohistochemical examination was related to: (1) the
      scarcity of neoplastic cells which were scattered among hematopoietic cells; (2)
      the difficulty of distinguishing malignant cells from immature hematopoietic
      elements; and (3) the absence of alteration of the reticulin network. The authors
      observed a significant association between marrow infiltration and the presence
      of hematologic abnormalities (mostly anemia or cytopenias) at diagnosis, both in
      children and adult patients. More importantly, a significant lower survival was
      seen in patients with bone marrow involvement compared to those without bone
      marrow involvement. Immunohistochemistry with anti-CD30 and anti-EMA antibodies
      should be performed systematically in bone marrow biopsies from patients with ALC
      lymphoma to reliably identify the presence of bone marrow involvement that
      appears to carry a poor prognosis.

PMID- 7817953
TI  - Performance of the Coumatrak system in a large anticoagulation clinic.
AB  - There is a need to monitor anticoagulation accurately, inexpensively, and
      rapidly. The accuracy and precision of a simple fingerstick method was studied in
      a large outpatient anticoagulation clinic using the Coumatrak method. The
      Coumatrak apparatus has been studied in the home setting, and three recent
      reports suggest that it is practical, accurate, and possibly superior to the
      standard method. These results differ from recently published studies. This
      technique was found to be less than acceptable in precision and accuracy. This
      method requires further study before it can be recommended for wide-spread use in
      making decisions for patient care.

PMID- 7817954
TI  - The use of occlusal indices: a European perspective.
AB  - Although occlusal indices are used in connection with public health orthodontic
      programs in some states, their adoption in everyday practice in the United States
      is extremely limited. On the other hand, indices are used extensively in Northern
      Europe, especially in determining access to public health orthodontics or the
      level of third party copayment. This article describes the development and
      validation of two new indices, IOTN (an index of treatment need) and PAR (an
      index of treatment outcome). Their application in a series of studies has led us
      to conclude that occlusal indices have a role in resource allocation and
      planning, promoting treatment standards, identifying prospective patients, and
      informed consent.

PMID- 7817955
TI  - Foundations of excellence: the ABO in review--1984-1994.

PMID- 7817956
TI  - Computerized imaging, is it for you?

PMID- 7817957
TI  - Direct light transmittance through ceramic brackets.
AB  - The objective of this study was to investigate the degree of direct light
      transmittance (%T) of various types of esthetic brackets and to correlate these
      values with their structure, morphologic factors, and composition. Eight types of
      brackets were used in the study; six brackets of each type were tested. An
      ultraviolet-visible spectroscopic direct transmission analysis was performed at
      320 to 700 nm wavelength range. From each spectrum, the %T corresponded to the
      peak absorbance wavelength of the photoinitiator of the polymerization was
      recorded (468 nm). Recorded data were analyzed with one-way analysis of variance
      and Scheffe's test at alpha = 0.05 significance level. In addition, scanning
      electron microscope (SEM) images were used to reveal the structure and
      morphologic factors of the brackets tested. Highest %T values (Mean +/- 1 SD)
      were obtained from a monocrystal type of bracket (Starfire ["A" Company, San
      Diego, Calif.] 35.02 +/- 1.59%), followed by a polycrystalline (Fascination
      [Dentaurum, Pforzhein, Germany] 5.70 +/- 1.41%) and a ceramic/polycarbonate base
      one (Ceramaflex [TP Orthodontics, Inc., La Porte, Ind.] 4.02 +/- 0.96%). Also
      other brands presented the following data: Allure (GAC, Central Islip, N.Y.) 3.62
      +/- 0.5%; Transcend 2000 (Unitek/3M, Monrovia, Calif.) 2.62 +/- 0.5%; Fascination
      (edgewise) (Dentaurum, Pforzhein, Germany) 1.97 +/- 0.69%; Lumina (Ormco,
      Glendora, Calif.) 1.57 +/- 0.5%; Signature (RMO, Denver, Colo.) 1.22 +/- 0.5%.
      The results showed that the structure, morphologic factors, and composition of
      the brackets tested were found to affect direct light transmission
      significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7817958
TI  - Relative kinetic frictional forces between sintered stainless steel brackets and
      orthodontic wires.
AB  - The level of kinetic frictional forces generated during in vitro translation at
      the bracket-wire interface were measured for two sintered stainless steel
      brackets as a function of two slot sizes, four wire alloys, and five to eight
      wire sizes. The two types of sintered stainless steel brackets were tested in
      both 0.018-inch and 0.022-inch slots. Wires of four different alloy types,
      stainless steel (SS), cobalt chromium (Co-Cr), nickel-titanium (Ni-Ti), and beta
      titanium (beta-Ti), were tested. There were five wire sizes for the 0.018-inch
      slot and eight wire sizes for the 0.022-inch slot. The wires were ligated into
      the brackets with elastomeric ligatures. Bracket movement along the wire was
      implemented by means of a mechanical testing instrument, and time dependent
      frictional forces were measured by a load cell and plotted on an X-Y recorder.
      For most wire sizes, lower frictional forces were generated with the SS of Co-Cr
      wires than with the beta-Ti or Ni-Ti wires. Increase in wire size generally
      resulted in increased bracket-wire friction. There were no significant
      differences between manufacturer for the sintered stainless steel brackets. The
      levels of frictional force in 0.018-inch brackets ranged from a low of 46 gm with
      0.016-inch Co-Cr wire to a high of 157 gm with 0.016 x 0.025-inch beta-Ti wire.
      In comparing the data from a previous study by Kapila et al. 1990 performed at
      OUHSC with the same apparatus, the friction of sintered stainless steel brackets
      was approximately 40% to 45% less than the friction of the conventional stainless
      steel brackets.

PMID- 7817959
TI  - Dentofacial and soft tissue changes in Class II, division 1 cases treated with
      and without extractions.
AB  - The purpose of this study was to compare the changes in subjects with Class II
      division 1 malocclusions treated with and without the extraction of four first
      premolars. Lateral cephalograms on 91 patients (44 extraction and 47
      nonextraction) were evaluated at three stages: pretreatment, posttreatment, and
      approximately 2 years after treatment. The present findings indicate that before
      treatment, the upper and lower lips were more protrusive relative to the esthetic
      plane among the subjects treated with four first premolar extractions. After
      treatment the upper and lower lips were more retrusive in the extraction group,
      and more protrusive in the nonextraction groups. The extraction group tended to
      have straighter faces and slightly more upright maxillary and mandibular
      incisors, whereas the nonextraction group had the opposite tendencies. The
      average soft tissue and skeletal measurements for both groups were close to the
      corresponding averages derived from the Iowa normative standards. In general,
      differences between the groups after treatment were preserved into retention. The
      present findings indicate that the extraction or nonextraction decision, if based
      on sound diagnostic criteria, seem to have no deleterious effects on the facial
      profile.

PMID- 7817960
TI  - The daily rhythm of tooth eruption.
AB  - A video microscope system, which can resolve tooth movements to 1 to 2 microns,
      was used to monitor the eruption of 17 human maxillary second premolars in the
      prefunctional phase. Eruptive movement was detected by the change in position of
      an optical ruling on the erupting tooth relative to a reference ruling on the
      occluding adjacent teeth. Eruption was observed as the teeth erupted toward the
      occlusal plane over approximately a 41-hour period, from late Friday afternoon
      until Sunday noon. Half hourly observations were made during a 6 to 8-hour
      continuous laboratory session, which was during the day (9 AM to 5 PM) for nine
      of the subjects, and during the evening (5 to 11 PM) for eight. A similar pattern
      of eruption was seen for all subjects. The tooth intruded from before to after
      dinner on the first day, erupted significantly overnight, ceased eruption and
      approximately maintained its position during the next day, and erupted again
      during the second night. On the average, a slight intrusion was observed during
      the day, and statistically significant intrusion was associated with breakfast
      and dinner. Eruption occurred during the evening observation period, and the rate
      of evening eruption was significantly greater in children who were supine and
      relaxed than those who were upright and active. The 24-hour eruption rate was
      slower for teeth that were within 1.5 mm of the occlusal plane. The circadian
      eruption rhythm may be related to fluctuations of hormonal levels that affect
      metabolic activities within the periodontal ligament. It is also possible that a
      transient reduction in pressures by the cheeks, lips, and tongue during periods
      of rest allows eruption to occur then.

PMID- 7817961
TI  - Average surface remodeling of the maxillary base and the orbital floor in female
      subjects from 8 to 25 years. An implant study.
AB  - The present study aimed to analyze the surface remodeling of the maxilla by the
      method of metallic implants. The sample comprised 14 series of lateral
      cephalometric films of girls, and was derived from the files of the implant study
      of Bjork. Implants had been inserted below the anterior nasal spine and on the
      lower anterior surfaces of the zygomatic arches. Various types of malocclusion
      were represented in the sample, but records during periods of orthodontic
      treatment and retention were excluded from the analysis. No subjects with
      craniofacial anomalies were included. The final sample comprised 155 radiographs
      in the age range 8 to 25 years. In addition to the anatomically defined reference
      points, six fiducial points and two implant points in the maxilla were digitized
      from each film. Data were debugged by comprehensive numerical and graphical
      procedures. The average relocation of the reference point subspinale (ss, Down's
      A point) was about 4.5 mm down and 0.5 mm forward from 8 to 25 years, whereas the
      reference point spinal (sp, ANS) was relocated about 4.5 mm down and 1 mm
      forward. The reference point pterygomaxillare (pm, PNS) was relocated 6 mm
      backward and 1.5 mm down by surface remodeling. The relocation of the sp and pm
      points resulted in an angular remodeling of the palatal plane of 2.5 degrees
      (backward). At the same time the maxillary complex rotated -1.5 degrees (forward)
      in relation to the anterior cranial base, resulting in a 1 degrees increase in
      the inclination of the palatal plane to the anterior cranial base. The orbital
      floor showed an average relocation of about 2.5 mm up and 2 mm backward by
      surface apposition, partly masking both the downward and forward sutural
      translation and the average forward growth rotation of the maxilla. Because of
      the angular remodeling of the palatal plane and the surface apposition on the
      hard palate, it is recommended that great caution be exerted in the
      interpretation of clinical treatment analyses based on superimposition on lines
      or structures defined by the anatomy of the bony palate during the period of
      growth.

PMID- 7817962
TI  - Skeletal maturation evaluation using cervical vertebrae.
AB  - Lateral cephalometric and left hand-wrist radiographs from the Bolton-Brush
      Growth Center at Case Western Reserve University were reviewed a posteriori to
      develop a cervical vertebrae maturation index (CVMI). By using the lateral
      profiles of the second, third and fourth cervical vertebrae, it was possible to
      develop a reliable ranking of patients according to the potential for future
      adolescent growth potential.

PMID- 7817963
TI  - Craniofacial structure in children with juvenile chronic arthritis (JCA) compared
      with healthy children with ideal or postnormal occlusion.
AB  - The aim of the present study was to evaluate the influence of condylar
      destruction on the craniofacial growth of children with juvenile chronic
      arthritis (JCA) and to compare their craniofacial structure with that of healthy
      children with ideal or postnormal occlusion. Thirty-five children (7 to 16 years)
      affected by JCA were compared with 136 children (7 to 16 years) with normal
      facial structure and occlusion (ideal group) and 62 children (7 to 12 years) with
      postnormal occlusion (postnormal group). Panoramic radiographs and lateral
      cephalograms were taken to detect condylar lesions and analyze facial structure.
      Multiple regression analysis was applied to test the possible relationships
      between the groups. The present study largely confirms earlier findings that the
      JCA group has a characteristic craniofacial structure. Their structure differed
      not only from the facial characteristics of children with ideal, but also to some
      extent, from children with postnormal occlusion. Furthermore, the craniofacial
      structure of children with JCA varied greatly, and radiographs showed that the
      most extreme craniofacial changes, particularly the mandibular structure, were
      associated with condylar lesions. In conclusion, the arthritic condylar lesions
      seem to be the main etiologic reason for the altered facial structure and changes
      in the occlusion in children with JCA. Influences of other factors, such as
      masticatory muscular function, are also discussed.

PMID- 7817964
TI  - Longitudinal growth changes in the sagittal relationship of maxilla and mandible.
AB  - This is a longitudinal study of the growth pattern in sagittal linear
      measurements at points A, B, and pogonion relative to the pterygoid vertical
      plane in a Class I sample. Serial cephalometric radiographs were traced and
      digitized at ages 6, 12, 18, and 24 years. The results indicated that between the
      ages of 6 and 24 years there was a total growth increment of 6.07, 7.53, and
      11.17 mm at points A, B, and pogonion, respectively, in the female Class I sample
      and 9.49, 11.65, and 16.21 mm at points A, B, and pogonion, respectively, in the
      male sample. Although the actual change in length of these measurements was
      larger in the male subjects than in the female subjects, in terms of percentage
      of growth increment in each of these three measurements from age 6 to 24 years,
      the anterior movement at point B relative to point A, and at pogonion relative to
      points B and A was approximately the same for both male and female subjects. When
      each of the subjects in both male and female samples was rank-ordered according
      to the size at age 6 years, considerable individual variation was noticeable for
      most persons within the group. The individual variation in growth pattern in each
      of the different measurements continues to raise questions about growth
      prediction and its application in visual treatment objectives.

PMID- 7817965
TI  - Vertical considerations in diagnosis and treatment. A surgical orthodontic case
      report.
AB  - The vertical considerations that must be made during diagnosis and subsequent
      treatment are discussed. The treatment planning procedure and the subsequent
      treatment of a difficult malocclusion that required comprehensive orthodontics
      with surgical intervention are presented.

PMID- 7817966
TI  - Damp housing and childhood respiratory symptoms: the role of sensitization to
      dust mites and molds.
AB  - In 1990, a case-control study was conducted in the Netherlands into the
      association between damp housing, childhood respiratory symptoms, and
      sensitization to house dust mites and mold allergens. In this study, 259 children
      with chronic respiratory symptoms and 257 control children were involved. Total
      serum immunoglobulin E (IgE) and specific IgE against house dust mites and a
      mixture of molds were determined. A visual inspection for signs of home dampness
      was performed in all homes. A questionnaire was given to the parents of the
      children to elicit information about the presence of signs of dampness in the
      previous 2 years and about risk factors for childhood respiratory disease. In the
      case group, 94 children had elevated serum IgE levels to house dust mites and 24
      children to the mixture of molds. In the control group, house dust mite allergy
      was found in 31 children and mold allergy in two children. In a crude analysis,
      cases were slightly more likely to have been living in homes where damp or mold
      was reported or observed than were the controls. In cases as well as controls,
      home dampness was associated with increased sensitization to dust mites and
      molds. There was no relation between home dampness and case-control status after
      stratification for sensitization, however. Restriction of the analysis to cases
      with elevated serum IgE levels against dust mites and/or molds, and to controls
      without elevated serum IgE, increased the odds ratios, and several became
      significant at p < 0.05. This supports a connection between damp housing and
      sensitization to dust mites and/or molds and childhood respiratory
      symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7817967
TI  - The association of ambient air pollution with twice daily peak expiratory flow
      rate measurements in children.
AB  - A stratified sample of 83 children living in Uniontown, Pennsylvania, reported
      twice daily peak expiratory flow rate (PEFR) measurements on 3,582 child-days
      during the summer of 1990. Upon arising and before retiring, each child recorded
      the time, three PEFR measurements, and the presence of cold, cough, or wheeze
      symptoms. Ambient air pollution, including particle-strong acidity, was measured
      separately during the day (8 a.m. to 8 p.m.) and at night. Each child's maximum
      PEFR for each session was expressed as the deviation from his or her mean PEFR
      over the study and adjusted to a standard of 300 liters/minute. The session
      specific average deviation was then calculated across all of the children. A
      second-order autoregressive model for PEFR was developed, which included a
      separate intercept for evening measurements, trend, temperature, and 12-hour
      average air pollutant concentration weighted by the number of hours each child
      spent outdoors during the previous 12-hour period. The results are expressed in
      terms of the interquartile range for each pollutant. A 12-hour exposure to a 125
      nmol/m3 increment in particle-strong acidity was associated with a -2.5
      liters/minute deviation in the group mean PEFR (95% confidence interval (CI) -4.2
      to -0.8) and with increased cough incidence (odds ratio (OR) = 1.6, 95% CI 1.1 to
      2.4). A 30-ppb increment in ozone for 12 hours was associated with a similar
      deviation in PEFR levels (-2.8, 95% CI -67 to 1.1). The association between PEFR
      and particle-strong acidity was observed among the 60 children who were reported
      as symptomatic on the prior symptom questionnaire (-2.5, 95% CI -4.5 to -0.5).
      The authors conclude that summer occurrences of excessive acid aerosol and
      particulate pollution are associated with declines in peak expiratory flow rates
      in children.

PMID- 7817968
TI  - Magnetic field exposure in relation to leukemia and brain cancer mortality among
      electric utility workers.
AB  - Reports of leukemia and brain cancer among men in electrical occupations suggest
      a small increase in risk, but most previous studies have failed to classify
      magnetic field exposure accurately or to consider potential confounders. The
      authors conducted an historical cohort mortality study of 138,905 men employed at
      five large electric power companies in the United States between 1950 and 1986
      with at least 6 months of work experience. Exposure was estimated by linking
      individual work histories to data from 2,842 workshift magnetic field
      measurements. Mortality follow-up identified 20,733 deaths based on 2,656,436
      person-years of experience. Death rates were analyzed in relation to magnetic
      field exposure history with Poisson regression. Total mortality and cancer
      mortality rose slightly with increasing magnetic field exposure. Leukemia
      mortality, however, was not associated with indices of magnetic field exposure
      except for work as an electrician. Brain cancer mortality was modestly elevated
      in relation to duration of work in exposed jobs and much more strongly associated
      with magnetic field exposure indices. Brain cancer risk increased by an estimated
      factor of 1.94 per microtesla-year of magnetic field exposure in the previous 2
      10 years, with a mortality rate ratio of 2.6 in the highest exposure category. In
      contrast to other studies, these data do not support an association between
      occupational magnetic field exposure and leukemia but do suggest a link to brain
      cancer.

PMID- 7817969
TI  - Environmental interventions in developing countries: interactions and their
      implications.
AB  - This study assesses the effect of drinking water quality on diarrheal disease in
      good and poor sanitary conditions using a random sample of 2,355 Filipino infants
      over the first year of life. The study provides powerful confirmation of the
      importance of environmental factors on diarrhea: The effects of water quality,
      household sanitation, and community sanitation are strong, consistent, and
      statistically significant. The positive impact of improved water quality is
      greatest for families living under good sanitary conditions, with the effect
      statistically significant when sanitation is measured at the community level but
      not significant when sanitation is measured at the household level. Improving
      drinking water quality would have no effect in neighborhoods with very poor
      environmental sanitation; however, in areas with better community sanitation,
      reducing the concentration of fecal coliforms by two orders of magnitude would
      lead to a 40 percent reduction in diarrhea. Providing private excreta disposal
      would be expected to reduce diarrhea by 42 percent, while eliminating excreta
      around the house would lead to a 30 percent reduction in diarrhea. The findings
      suggest that improvements in both water supply and sanitation are necessary if
      infant health in developing countries is to be improved. They also imply that it
      is not epidemiologic but behavioral, institutional, and economic factors that
      should correctly determine the priority of interventions.

PMID- 7817970
TI  - Clinical infections in the noninstitutionalized geriatric age group: methods
      utilized and incidence of infections. The Pittsburgh Good Health Study.
AB  - Because noninstitutionalized senior citizens comprise over 95% of the population
      65 years of age and older, their health needs are a major concern. Data regarding
      infections in this population including the epidemiology, morbidity, and
      mortality are lacking. The authors recruited a study population of 417 free
      living persons, all 65 years of age or older, from two neighborhoods in
      Pittsburgh, Pennsylvania. After the collection of self-reported baseline
      information from these persons, they were monitored for all clinical infections
      for 2 years, beginning July 1986 and through June 1988, using clinic visits,
      hospitalizations, or phone calls when needed. The baseline information showed the
      study population of 417 persons to be comparable with a neighborhood comparison
      group and with established populations for epidemiologic studies of the elderly
      in three other states. The 24 months of infection surveillance yielded 494
      diagnosed infections in 224 or 54% of the subjects. Respiratory infections were
      most frequent with 259 or 52% of the total, followed by genitourinary infections
      with 24%, skin infections with 18%, gastrointestinal infections with 4%, and
      other types of infection with 2%. By comparing 22 self-reported baseline
      conditions with the occurrence of infection, 10 historic factors were
      univariately significant for infection. Of these 10 factors, only history of a
      lung problem (relative risk = 1.7, 95% confidence interval (CI) 1.1-2.9) and
      history of difficulty controlling urination (relative risk = 2.7, 95% CI 1.3-4.9)
      were statistically significant in multivariate analysis. To our knowledge, this
      study represents the first prospective data on infections in the
      noninstitutionalized elderly. The data demonstrate the wide variety of infections
      that occurred in this population and suggest that persons with a history of any
      one of several medical problems were possibly at greater risk for infection.

PMID- 7817971
TI  - Epidemiology of gallstone disease in Italy: prevalence data of the Multicenter
      Italian Study on Cholelithiasis (M.I.COL.)
AB  - This study was designed to obtain a general overview of gallstone disease in
      Italy. A total of 18 cohorts in 10 Italian regions were enrolled in this survey.
      Four cohorts were excluded from analysis because of a participation rate of less
      than 50 percent. Field activities started in December 1984 and terminated in
      April 1987. A precoded questionnaire was administered to each subject by a
      trained member of the medical staff. Participants underwent an ultrasonographic
      examination of the upper abdomen and blood sampling. Each research group was
      provided with an identical ultrasonographic machine. Standardized criteria were
      established for both the examination and diagnosis. The inter- and intraobserver
      variation in the ultrasonographic procedure was assessed using a reliability
      study. The overall kappa score for interobserver agreement was good (0.649),
      while intraobserver agreement was good or excellent (kappa scores > 0.60) in 75
      percent of the observers. A total of 29,739 of the 46,139 (64.4 percent) enrolled
      subjects were examined. Among those with a clear-cut definition of the
      gallbladder status, 6.5 percent of the males and 10.5 percent of the females had
      gallstones. Additional 3.0 and 8.4 percents, respectively, had already undergone
      cholecystectomy. Prevalence of gallstone disease (gallstones plus
      cholecystectomy) increased linearly with age in both sexes. Among subjects with
      gallstones, 76.7 percent of men and 72 percent of women were not aware of having
      gallstones; 87.0 percent of men and 84.9 percent of women were asymptomatic. This
      study confirms that gallstone disease is a highly prevalent condition. Gallstones
      rarely cause symptoms, and subjects are mostly unaware of their presence.

PMID- 7817972
TI  - Estimation of current human immunodeficiency virus incidence rates from a cross
      sectional survey using early diagnostic tests.
AB  - In sharp contrast to the considerable worldwide epidemiologic data available on
      acquired immunodeficiency syndrome incidence and human immunodeficiency virus
      (HIV) seroprevalence, there is relatively little information about current levels
      of HIV incidence rates. The authors suggest a novel approach for estimating
      current HIV incidence rates based on a single cross-sectional survey and on an
      epidemiologic model. The approach is based on diagnostic tests for HIV p24
      antigen to identify individuals in the preantibody or window period (time between
      exposure to HIV and appearance of detectable HIV antibodies). Individuals in the
      preantibody period are likely to have been infected very recently because the
      duration of the preantibody period is relatively short. The authors report data
      on the duration of p24 antigenemia prior to HIV seroconversion. This duration
      together with the prevalence of p24 antigenemia obtained from a cross-sectional
      survey are used in an epidemiologic model to estimate current incidence rates.
      This approach of estimating incidence rates may be especially useful in
      developing countries and high-risk populations in which it is difficult to follow
      cohorts to identify seroconverters, and in the design of vaccine efficacy studies
      in which current incidence rates are crucial for calculating sample sizes.

PMID- 7817973
TI  - Re: "Components of drinking water and risk of cognitive impairment in the
      elderly".

PMID- 7817974
TI  - Re: Respiratory and irritant health effects of ambient volatile organic
      compounds: the Kanawha County Health Study.

PMID- 7817975
TI  - Re: "Bacterial pneumonia in adult populations with human immunodeficiency virus
      (HIV) infection".

PMID- 7817976
TI  - Causes. 1976.

PMID- 7817977
TI  - Impact of parental smoking on the prevalence of wheezing respiratory illness in
      children.
AB  - To quantitatively assess environmental tobacco smoke exposure from parental
      smoking as a risk factor for asthma or wheezing in childhood, and to derive
      estimates of excess asthma/wheezing lower respiratory tract illness cases
      attributable to this risk factor, a cross-sectional analysis of the 1987 National
      Medical Expenditure Survey (a national probability sample of the civilian,
      noninstitutionalized US population) was undertaken. The National Medical
      Expenditure Survey included 7,578 children and youth less than 18 years of age in
      a stratified cluster sampling of US households. After using logistic regression
      analysis to control for sex, race/ethnicity, region of residence, population
      density, poverty status, maternal educational level, family size, and father's
      current smoking status, children whose mothers smoked at the time of the survey
      were more likely than children of nonsmoking mothers to experience wheezing
      respiratory illness (odds ratio = 1.36, 95% confidence interval 1.14-1.62). The
      association was greatest among children less than 2 years of age. The authors'
      estimate of the attributable risk in the US population indicates that maternal
      smoking is responsible for approximately 380,000 excess cases of childhood
      asthma/wheezing lower respiratory tract illness or 7.5% of the total number of
      such symptomatic children.

PMID- 7817979
TI  - Effect of intestinal tapering and lengthening on intestinal structure and
      function.
AB  - BACKGROUND: Intestinal lengthening (TL) is increasingly performed for the short
      bowel syndrome. Our aim was to evaluate the effect of TL on canine intestinal
      structure and function. METHODS: Two groups of 5 dogs had 75% distal intestinal
      resection. Twelve weeks later, serosal electrodes were placed in one group (RO)
      and tapering and lengthening of 10 to 15 cm distal intestine and electrode
      placement was performed in the other group (TL). Nutritional status and
      intestinal absorption, motility, and hormone release were assessed every 4 weeks
      for 12 weeks after the second procedure. RESULTS: The animals with the
      lengthening had diminished body weight (75% +/- 2% versus 81% +/- 4%, P < 0.05)
      and albumin levels (2.4 +/- 0.2 g/dL versus 2.9 +/- 0.5 g/dL, P < 0.05) and
      impaired absorption (stool fat 18% +/- 6% versus 10% +/- 3%, P < 0.05) compared
      with those that had undergone resection alone. The intestinal adaptive response
      was blunted in the TL group (villus height 328 +/- 90 microns versus 410 +/- 36
      microns, P < 0.05). Transit time was prolonged 4 and 8 weeks (19 +/- 6 min and 18
      +/- 5 min, respectively, versus 11 +/- 3 min, P < 0.05) after TL. Myoelectrical
      recordings showed a drop in slow wave frequency and impaired migration of Phase
      III of the migrating motor complex within the tapered and lengthened segments (P
      < 0.05). Both fasting and postprandial serum gastrin levels were two times
      greater in the TL group (P < 0.05). Enteroglucagon levels were increased after
      resection alone; this increase was attenuated by more than 50% in the TL group (P
      < 0.05). The somatostatin response to feeding was substantially greater in the TL
      animals. CONCLUSIONS: TL impairs nutritional status and intestinal absorption and
      adaptation following massive resection. The changes in absorption and transit may
      be related, in part, to motor disruption and hypergastrinemia. The impaired
      adaptation is possibly related to decreased enteroglucagon and increased
      somatostatin levels.

PMID- 7817978
TI  - Alterations in hepatocyte insulin binding in chronic pancreatitis: effects of
      pancreatic polypeptide.
AB  - BACKGROUND: Hepatic insulin resistance has previously been demonstrated in
      chronic pancreatitis, and has been shown to be ameliorated by pancreatic
      polypeptide administration. Insulin binding was investigated in chronic
      pancreatitis induced by infusion of oleic acid into the pancreatic duct of rats.
      METHODS: Acute pancreatitis was induced in 12 200 to 225 g 8-week-old male
      Sprague-Dawley rats by intubation of the main bile duct at its junction with the
      duodenum through a small midline abdominal incision, and infusion of 99% oleic
      acid 0.015 mL/min for 4 minutes, with an additional 4 minutes dwell-time after
      infusion. Sham-operated animals served as controls. After 6 weeks, chronic
      pancreatitic and sham-operated animals received either intraperitoneal bovine
      pancreatic polypeptide or saline vehicle for 5 days. Intraduodenal glucose
      tolerance tests (GTT) were performed in fasted animals, after which tissues were
      procured. Insulin receptors were isolated from solubilized hepatocyte and rectus
      abdominus membranes and competitive-binding studies were performed by incubation
      with 125I-insulin. Dissociation coefficients (Kd) and maximum binding capacities
      (Bmax) for high-affinity receptors were derived from Scatchard analyses. RESULTS:
      Bmax and Kd in muscle were not altered in animals with chronic pancreatitis. In
      liver, Bmax was significantly less in rats with chronic pancreatitis given saline
      than in sham-operated rats given saline (17.0 +/- 6.3 versus 47.6 +/- 13.1
      fmol/mg protein; data are mean +/- SEM). Pancreatic polypeptide administration
      increased hepatic Bmax in rats with chronic pancreatitis (to 47.2 +/- 9.8 fmol/mg
      protein), but had no significant effect in sham-operated rats. Receptor affinity
      was not significantly different in rats with chronic pancreatitis or rats who
      underwent sham operations and was unaltered by the administration of pancreatic
      polypeptide. The integrated plasma glucose response during the GTT was reduced by
      pancreatic polypeptide administration in rats with chronic pancreatitis (29.5 +/-
      15.0 mg/dL per minute versus 69.0 +/- 21.8 in chronic pancreatitis without
      pancreatic polypeptide), but was not significantly altered in sham-operated
      animals. CONCLUSION: Diminished expression of high-affinity receptors on the
      hepatocyte membrane may contribute to hepatic insulin resistance in chronic
      pancreatitis. In this model, pancreatic polypeptide improved glucose tolerance
      and increased receptor capacity to the level observed in livers from
      nonpancreatitic animals.

PMID- 7817980
TI  - Does neomucosa induced by small bowel stem cell transplantation have adequate
      function?
AB  - Small intestinal epithelium digests and absorbs nutrients. Crypt stem cell
      transplantation can generate neomucosa with normal morphology, but the digestive
      and absorptive capacities of this neomucosa are unknown. This study evaluates
      stem cell induced neomucosal brush border digestive enzyme activity and nutrient
      transport function. Rodent small intestinal epithelial stem cells were isolated
      by enzymatic digestion, then grafted to inbred recipients. Grafts were retrieved
      at 25 days, and apical brush border membrane vesicles prepared for quantitative
      assays. Neomucosal lactase, sucrase, aminopeptidase N, and alkaline phosphatase
      activity was determined by incubation with enzyme specific substrate. Neomucosal
      sodium dependent D-glucose transport was evaluated by incubation with D-[U-14C]
      glucose. Comparative assays were performed in age-matched control intestine.
      Neomucosal digestive enzyme activities and D-glucose transport were all similar
      in neomucosa and control small intestine.

PMID- 7817981
TI  - Down-regulation of transforming growth factor beta receptor type I, II, and III
      during liver regeneration.
AB  - BACKGROUND: After partial hepatectomy (PH), it has been shown that hepatocytes
      are resistant to the mitoinhibitory effects of transforming growth factor beta
      (TGF-beta). Three types of TGF-beta receptors have been characterized in mammals.
      MATERIALS AND METHODS: In this study, changes in the protein and mRNA expression
      of TGF-beta types I, II, and III receptors relative to DNA synthesis were studied
      as a function of time after PH in the rat. RESULTS: There was a significant
      decrease in the protein and mRNA for all three receptor subtypes immediately
      after PH. All three receptors reached a nadir at 24 hours after PH, which
      correlated to the time of peak DNA synthesis. The type II receptor recovered to
      preoperative levels by 120 hours after PH, whereas the types I and III receptors
      remained at 60% of prehepatectomy levels. Sham-operated rats did not experience a
      significant drop in receptor protein or mRNA levels. CONCLUSIONS: This decrease
      in TGF-beta type II receptor expression may account for the reduction in the
      sensitivity of hepatocytes to TGF-beta after PH. Furthermore, the TGF-beta
      receptors appear to represent a class of immediate-early genes that are
      negatively, rather than positively, regulated after PH.

PMID- 7817982
TI  - Cytokines in Crohn's colitis.
AB  - BACKGROUND: Increasing evidence points to a pathologic role for cytokines in
      Crohn's colitis. Levels of cytokines are increased in diseased segments of colon
      in Crohn's colitis, but no one has studied the concentration of cytokines in
      clinically and histologically nondiseased segments. METHODS: Mucosal biopsies
      were obtained from 7 patients with active segmental Crohn's colitis and from 7
      controls without inflammatory bowel disease. The concentration of Interleukin
      (IL)-1 beta, IL-2, IL-6, and IL-8 in patients and controls were determined using
      enzyme linked immunosorbent assay and compared. Histologic sections were also
      performed to confirm diseased and nondiseased segments of colon. RESULTS: The
      concentrations of IL-1 beta, IL-6, and IL-8 were significantly higher in the
      involved segments of colon (10.3 +/- 4.1, 3.7 +/- 1.0, 34.4 +/- 6.9 picograms
      [pg] per mg) when compared to controls (1.8 +/- 0.5, 1.1 +/- 0.5, 5.3 +/- 1.0
      pg/mg). The concentrations of IL-1 beta, IL-2, and IL-8 (8.5 +/- 2.9, 5.3 +/-
      1.2, 26.3 +/- 8.8 pg/mg) in normal appearing segments of colon of patients with
      Crohn's colitis were also significantly higher than in controls, whose IL-2 level
      was 2.0 +/- 0.5 pg/mg. IL-1 beta and IL-8 were significantly more concentrated in
      both the involved and uninvolved colonic segments of patients with Crohn's
      colitis compared to controls. IL-2 and IL-6 were also more concentrated in
      Crohn's patients than in controls, but not significantly. The differences in
      interleukin concentrations between involved and uninvolved segments of colon in
      patients with segmental Crohn's colitis were not significant. CONCLUSIONS:
      Although Crohn's colitis is often a segmental disease, concentrations of IL-1
      beta and IL-8 are increased throughout the entire colon. These observations
      reinforce the hypothesis that Crohn's colitis involves the whole colon even when
      this is not apparent clinically or histologically.

PMID- 7817983
TI  - Functional assessment of ileal pouch-anal anastomotic techniques.
AB  - BACKGROUND: Recent advances in ileal pouch-anal anastomotic (IPAA) technique
      include the substitution of a double stapled anastomosis for a mucosectomy and
      hand-sewn pouch-anal anastomosis, and the use of staples to construct a "J"
      shaped pouch rather than a hand-sewn "S" pouch in most cases. METHOD: To
      determine the impact these technical changes have had on pouch function, 235 IPAA
      patients with 15 to 155 months of follow-up (mean 70 months) were interviewed by
      telephone concerning pouch function and quality of life. Categorical responses
      were then evaluated by contingency table analysis to detect differences between
      mucosectomy (n = 157) and nonmucosectomy (n = 80) groups, and between J pouch (n
      = 50), S pouch with mucosectomy (n = 137), and S pouch nonmucosectomy (n = 30)
      subgroups. An index encompassing nine functional measures was used to quantify
      the overall impact of technique changes (optimal score 100). RESULTS: Stool
      frequency for mucosectomy patients was 7.2 movements/24 hours, compared to 7.1
      for nonmucosectomy patients. Elimination of a mucosectomy dramatically reduced
      nocturnal major incontinence (P < 0.001), nocturnal minor incontinence (P <
      0.001), daytime minor incontinence (P = 0.03), and day-time pad use (P = 0.002).
      Nonmucosectomy patients had a better functional index score than had patients
      with an S pouch, even when only data from nonmucosectomy patients were analyzed
      (J = 95.5, S = 91.8, P = 0.009). CONCLUSIONS: Avoidance of a mucosectomy in the
      performance of an ileal pouch-anal anastomosis does not influence stool frequency
      but does significantly improve fecal continence and introduces no detectable
      morbidity associated with the retained rectal mucosa.

PMID- 7817984
TI  - Outcome of early surgical complications following ileoanal pouch operation
      without diverting ileostomy.
AB  - BACKGROUND: Many surgeons use a diverting ileostomy routinely following ileoanal
      pouch operation because they fear that complications may lead to permanent
      unsatisfactory pouch function or even death. We report the outcome of early
      surgical complications when ileoanal pouch operation is performed without a
      diverting ileostomy. We performed 74 consecutive ileoanal pouch operations since
      ileoanal pouch operations since October 1989 using a transition-zone-sparing
      stapled J pouch method. RESULTS: Of the 74 patients, 68 (92%) underwent the
      operation without a diverting ileostomy. Five of the 68 patients (7.4%) required
      reoperation within 30 days of operation. Pouch excision was necessary in 2
      patients (3%) for reasons not resulting from omitting the diverting ileostomy,
      and they now have excellent pouch function. CONCLUSION: Patients who required
      early reoperation and placement of a temporary diverting ileostomy did not suffer
      long-term consequences. The fear that early surgical complications following
      ileoanal pouch operation without diverting ileostomy are permanently detrimental
      is unjustified.

PMID- 7817985
TI  - Level of the anastomosis does not influence functional outcome after anterior
      rectal resection for rectal cancer.
AB  - Anorectal function was studied in 55 patients undergoing low anterior resection
      for rectal adenocarcinoma. Patients were examined preoperatively and 3 months
      postoperatively by anorectal manometry and standardized interview.
      Postoperatively, the patients showed, in general, an impairment of anorectal
      functions. After 3 months, continence for flatus was defective, the ability to
      discriminate flatus from feces, and the ability to defer defecation were
      compromised. Stool frequency was elevated, and anal resting pressure, squeeze
      pressure, and rectal compliance were decreased. The rectoanal inhibitory reflex
      was abolished in all patients. However, the two groups with the level of the
      anastomosis less than or equal to 6 cm (n = 27, range 3 to 6) and more than 6 cm
      (n = 28, range 7 to 10) above the anal verge showed no differences in manometric
      values, stool frequency, or fecal continence assessed by the interview. No
      correlation was found between the level of the anastomosis and manometric values
      and between the level of the anastomosis and stool frequency (regression analysis
      = not significant). We concluded that anorectal function after anterior resection
      and low colorectal anastomosis are not influenced by the remaining length of the
      rectum but by the surgical trauma to the sphincter and its innervation.

PMID- 7817986
TI  - Evaluation of a carboxymethylcellulose sponge for prevention of postoperative
      adhesions.
AB  - BACKGROUND: A novel lyophilized carboxy-methylcellulose (CMC) sponge has been
      developed for prevention of surgical wound adhesions. One potential mechanism for
      preventing abdominal adhesion is suppression of the cytokine transforming growth
      factor beta (TGF-beta) and other macrophage derived fibroblast stimulating
      factors that partially mediate adhesion formation. METHODS: To study the efficacy
      and mechanisms of action of the CMC sponge, we performed standard cecal
      denudation and abdominal wall apposition on rats. A CMC sponge or a commercially
      available adhesion preventive barrier (Interceed) was placed on the denuded
      surface. After 14 days, adhesion severity was graded blindly on a scale ranging
      from 0 (no adhesion) to 5 (severe adhesion). TGF-beta expression was determined
      by immunocytochemical staining. To assess the secretion of macrophage derived
      fibrogenic factors in control and CMC rats, labeled thymidine and proline uptake
      and hydroxyproline production were measured in NRK rat fibroblasts cultured with
      conditioned medium of peritoneal macrophages. RESULTS: The severity of adhesions
      in the CMC sponge group (0.7 +/- 0.3) was significantly lower than in the
      Interceed or control groups (2.2 +/- 0.3; 4.6 +/- 0.1). In control animals TGF
      beta expression in endothelium and fibroblasts was maximal on day 3. Neither CMC
      nor Interceed reduced this expression. Conditioned media derived from sponge
      exposed postsurgical peritoneal macrophages did not inhibit fibroblast growth or
      collagen formation. CONCLUSIONS: In this model the CMC sponge was more effective
      than Interceed in preventing postoperative adhesions. Its action was not due to
      inhibition of TGF-beta expression or macrophage derived fibrogenic factors. These
      data highlight the primary importance of local barrier effect in adhesion
      prevention.

PMID- 7817987
TI  - Hypercalcemia causes acute pancreatitis by pancreatic secretory block,
      intracellular zymogen accumulation, and acinar cell injury.
AB  - BACKGROUND: Because hypercalcemia is a known etiologic factor for human acute
      pancreatitis, studies of the pancreatic pathophysiology and pathomorphology of
      experimental hypercalcemia have potential clinical significance. MATERIALS AND
      METHODS: Rats received central venous infusion of either 0.6 mmol/kg per hour
      CaCl2 or 0.9% NaCl infusion for 12 hours. Pancreatic tissue samples were obtained
      and prepared for electron microscopy. Tissue homogenates were examined for DNA,
      lactate dehydrogenase (LDH), protein, amylase, and calcium contents. Basal or
      stimulated (cerulein 0.25 microL/kg per hour) pancreatic secretions were analyzed
      for volume, protein, and amylase output, as well as protein composition on sodium
      dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). RESULTS: The
      tissue calcium content and the ratio of LDH to DNA was unchanged after calcium
      infusion, but the ratios of total protein to DNA and of amylase to DNA were
      significantly larger. Basal output of pancreatic juice volume, protein, and
      amylase were significantly lower. SDS-PAGE of pancreatic juice revealed weakening
      of a 70,000-d band and appearance of lower molecular weight bands in two samples.
      Ultrastructural examination demonstrated accumulation of zymogen granules in the
      acinar cell, large autophagic vacuoles containing remnants of condensing
      vacuoles. CONCLUSIONS: These findings suggest that hypercalcemia induces
      pancreatic injury via a secretory block, accumulation of secretory proteins, and
      possibly activation of proteases.

PMID- 7817988
TI  - Dietary regulation of the hepatic system n glutamine transporter in tumor-bearing
      rats.
AB  - BACKGROUND: Hepatocytes possess a novel, plasma-membrane, sodium ion (Na+)
      independent, glutamine transporter (system n), which functions to transport
      glutamine out of the cell into the blood. In the tumor-bearing rat, the activity
      of system n increases but its regulation is unknown. We hypothesized that the
      increase in system n that occurs in rats with cancer was related to a fall in the
      circulating glutamine concentration. METHODS: Ten male rats underwent flank
      implantation with a cube of methylcholanthrene-induced fibrosarcoma cells and 10
      rats underwent a sham operation. After 9 days of standard diet, all rats were
      randomized to receive either a glutamine-enriched oral diet or an isonitrogenous
      diet without supplemental glutamine, for 1 week. Tumors and livers were harvested
      16 days postimplantation. Arterial blood samples were obtained from all animals.
      Hepatic plasma membrane vesicles were prepared and the carrier-mediated, Na(+)
      independent transport of glutamine was assayed. RESULTS: When compared to
      nontumor-bearing animals, tumor-bearing rats that were fed a control diet
      exhibited hypoglutaminemia and a 2.3-fold increase in the activity of system n.
      Glutamine dietary supplementation produced blood glutamine levels that were
      similar in both tumor-bearing and nontumor-bearing rats, apparently abrogating
      the increase in system n activity that was observed in tumor-bearing rats that
      were not fed supplemental glutamine. Tumor-bearing animals receiving supplemental
      glutamine had a decreased number of system n carriers (Vmax) in the hepatic
      plasma membrane compared to that of tumor-bearing animals receiving a control
      diet; this apparently abrogated the glutamine efflux rate. Glutamine feeding did
      not alter system n activity in nontumor-bearing controls. CONCLUSIONS: In the
      tumor-bearing animal model, system n is modulated by the circulating glutamine
      concentration. This is the first study that demonstrates the ability of
      specialized nutrition to "downregulate" transport activity in vivo. Provision of
      glutamine-enriched diets to the host with cancer may maintain hepatic glutamine
      levels and prevent host glutamine depletion.

PMID- 7817989
TI  - Quality of life, nutritional status, and gastrointestinal hormone profile
      following the Whipple procedure.
AB  - BACKGROUND: To compare the quality of life, nutritional status, and
      gastrointestinal profiles of post-Whipple patients and postcholecystectomy
      patients. METHODS: A cross-sectional survey of post-Whipple procedure patients
      and age- and sex-matched postcholecystectomy patients was performed. Quality of
      life was assessed using six instruments: Time Trade-off Technique, Direct
      Questioning of Objectives, Gastrointestinal Quality of Life Index, Sickness
      Impact Profile, Physician Global Assessment, and Visick Scale. A gastrointestinal
      symptomatology questionnaire was completed. Nutritional status was assessed by
      weight, the Subjective Global Assessment instrument, and skin anthropometry.
      Fasting and postprandial serum gastrin, somatostatin, insulin, pancreatic
      glucagon, enteroglucagon, and pancreatic polypeptide were measured. RESULTS: The
      quality of life and gastrointestinal function of the Whipple patients was
      excellent and was not significantly different from that of the control subjects.
      There were no significant differences in gastrointestinal symptomatology although
      5 Whipple patients complained of greasy bowel movements, and 1 patient reported
      difficulty maintaining weight. Despite this, nutritional status was within normal
      limits in all subjects. Six patients in the Whipple group followed a diabetic
      diet, 1 required insulin, and 3 required an oral hypoglycemic agent, whereas none
      of the control subjects were diabetic. There were no significant differences in
      the mean basal, peak, or integrated postprandial responses of the gut hormones
      with the exception of pancreatic polypeptide and gastrin (in patients having a
      standard Whipple procedure only). CONCLUSION: Quality of life and nutritional
      status are excellent in patients following a Whipple procedure.

PMID- 7817990
TI  - Endothelial-leukocyte interactions in the neutrophil cascade.

PMID- 7817991
TI  - Medical and surgical peer review.

PMID- 7817992
TI  - Hyperbaric oxygen treatment of necrotizing fasciitis.

PMID- 7817993
TI  - "Don't look back--something might be gaining on you".

PMID- 7817994
TI  - Correction of congenital indirect hyperbilirubinemia by small intestinal
      transplantation.
AB  - INTRODUCTION: Crigler-Najjar syndrome, type I, is a disease characterized by
      complete absence of hepatic bilirubin glucuronidation. The congenital indirect
      hyperbilirubinemia is due to an autosomal recessive deficiency of the enzyme,
      uridine diphosphate glucuronosyl transferase (UDPGT). The inbred homozygous Gunn
      rat is also deficient in UDPGT, exhibits unconjugated hyperbilirubinemia, and is
      an excellent animal model of the Crigler-Najjar syndrome. This study was
      performed to test the ability of transplanted intestine from normal Wistar rat
      donors to correct the deficiency in hepatic bilirubin conjugation. MATERIALS AND
      METHODS: In phase 1, Gunn rats underwent 40-cm heterotopic small-bowel
      transplants from either Wistar (experimental) or Gunn (control) rats. In phase 2,
      15- to 20-cm Wistar-to-Gunn jejunal transplants were placed either
      heterotopically or orthotopically (in intestinal continuity). All rats were
      treated with cyclosporin A (CsA), 5 mg/kg per day. Serum bilirubin levels were
      determined spectrophotometrically at weekly intervals posttransplantation. In
      phase 2, UDPGT activity was quantitated at 0, 2, 4, and 8 weeks using known
      quantities of bilirubin as substrate. RESULTS: Total bilirubin levels decreased
      significantly in the 40-cm heterotopic transplant recipient rats. From the
      initial values of 7.12 +/- 0.59 mg/dL, levels reached the nadir of 4.23 +/- 0.27
      mg/dL. A parallel drop in serum levels of indirect bilirubin was noted (5.04 +/-
      0.54 mg/dL to 2.74 +/- 0.23 mg/dL). After 6 weeks, bilirubin levels began to rise
      toward pretransplant values. In contrast, there was no significant change in
      bilirubin levels in the control Gunn-to-Gunn rats. Fifteen- to 20-cm heterotopic
      Wistar-to-Gunn transplants caused a qualitatively similar drop in total and
      indirect bilirubin levels. Orthotopic (in continuity) Wistar-to-Gunn transplants
      lowered serum bilirubin levels more rapidly, and the effect was sustained
      throughout the 8-week study period. By 1 week posttransplantation, total
      bilirubin levels dropped from 5.11 +/- 0.48 mg/dL to 2.41 +/- 0.16 mg/dL (P <
      0.05); data at 8 weeks averaged 1.84 +/- 0.35 mg/dL. Respective data for indirect
      bilirubin levels were 4.81 +/- 0.45 mg/dL, 2.26 +/- 0.18 mg/dL, and 1.35 +/- 0.39
      mg/dL. Wistar rat UDPGT activity in intestine and liver averaged 0.61 +/- 0.05
      and 1.88 +/- 0.06 mg bilirubin conjugated/mg tissue per hour, respectively.
      Enzyme activity in the transplanted intestine persisted throughout the course of
      the study. CONCLUSION: Transplants of small intestine with known UDPGT activity
      partially corrected the deficiency in Gunn rats and allayed the
      hyperbilirubinemia. Since the small intestine is known to contain small but
      significant amounts of a large number of predominantly hepatic enzymes, bowel
      transplantation may be an appropriate treatment for this and other similar
      genetic enzyme deficiencies.

PMID- 7817995
TI  - Factors affecting long-term outcome after hepatic resection for hepatocellular
      carcinoma.
AB  - BACKGROUND: Experience with hepatocellular carcinoma (HCC) is limited in the West
      and factors affecting outcome after resection are not clearly defined. METHODS:
      Between 1970 and 1992, 106 patients (including 74 Caucasians, 31 Orientals, and 1
      black) underwent hepatic resection for HCC at Memorial Sloan-Kettering Cancer
      Center. Clinical and histopathologic factors of outcome were analyzed. RESULTS:
      Cirrhosis was present in 33% and 95% were Child-Pugh A. Operative mortality was
      6%, 14% in cirrhotics versus 1% in non-cirrhotics (P = 0.013). Orientals had a
      higher prevalence of cirrhosis (68% versus 19%) (P < 0.0001) and smaller tumors
      (mean 8.7 cm versus 11.0 cm) (P = 0.028) compared to Caucasians. Overall survival
      was 41% and 32% at 5 and 10 years, respectively. By univariate analysis, survival
      was greater in association with the following: absence of vascular invasion (69%
      versus 28%, P = 0.002); absence of symptoms (66% versus 38%, P = 0.014); solitary
      tumor (53% versus 28%, P = 0.014); negative margins (46% versus 21%, P = 0.022);
      small tumor (< or = 5 cm) (75% versus 36%, P = 0.027); and presence of tumor
      capsule (69% versus 35%, P = 0.047). Ethnic origin, cirrhosis, necrosis and grade
      did not affect survival. By multivariate analysis, only vascular invasion
      predicted outcome (P = 0.0025, risk ratio 2.9). CONCLUSIONS: One third of
      patients resected for HCC can be expected to survive long-term. Except for a
      higher incidence of cirrhosis in Orientals, no major histopathologic or
      prognostic differences were noted between Orientals and Caucasians undergoing
      resection. Early cirrhosis (Child-Pugh A) did not adversely affect survival.
      Vascular invasion predicted long-term outcome.

PMID- 7817996
TI  - Hepatic resection for metastatic neuroendocrine carcinomas.
AB  - BACKGROUND: Metastatic neuroendocrine malignancies frequently cause
      incapacitating endocrinopathies, and metastases predominant in the liver. Hepatic
      resection of metastases from such tumors is attractive because the natural
      history of neuroendocrine tumors is protracted, clinical severity of the
      endocrinopathy correlates with tumor volume, and local and intrahepatic growth
      characteristics often allow complete resection. PATIENTS AND METHODS: To define
      the role of hepatic resection for metastatic neuroendocrine tumors, the records
      of 74 patients who underwent hepatic resection for such tumors between 1984 and
      1992 were reviewed. Neuroendocrine tumors were classified by site of origin and
      clinical endocrinopathy. Survival, and type and duration of symptomatic response,
      were assessed as the major outcomes of this study. RESULTS: There were 50
      carcinoid, 23 islet-cell, and 1 atypical neuroendocrine tumors. Resections
      included 36 hemihepatectomies or extended hepatectomies and 38 nonanatomic
      resections. Thirty-eight primary tumors were resected concomitantly.
      Perioperative mortality was 2.7% and morbidity was 24%. Four-year survival was
      73%. Overall postoperative symptomatic response rate was 90% with a mean duration
      of response of 19.3 months. CONCLUSIONS: Hepatic resection for metastatic
      neuroendocrine malignancies is safe, provides effective palliation, and probably
      prolongs survival.

PMID- 7817997
TI  - The utility of prophylactic laparoscopic cholecystectomy in transplant
      candidates.
AB  - BACKGROUND: This study addresses the impact of laparoscopic cholecystectomy prior
      to kidney or pancreas transplant. PATIENTS AND METHODS: Between January 1991 and
      July 1993, 551 patients were listed for transplant. Gallbladder ultrasound became
      part of the standard evaluation for all transplant candidates in October 1991.
      Pretransplant laparoscopic cholecystectomy was recommended for all patients found
      to have gallstones. To assess the benefit of this policy, patients transplanted
      prior to routine ultrasound (Group I; n = 88) were compared to those listed or
      transplanted after routine ultrasound (Group II; n = 406). RESULTS: In Group I,
      18% developed gallstone complications requiring surgery. Surgical morbidity
      occurred in 14% and mortality in 7% of these operations. Graft loss occurred in
      20% having biliary complications versus 7% among other recipients. In Group II,
      gallstones were detected in 10%, and 9% subsequently had laparoscopic
      cholecystectomy with no morbidity or mortality. CONCLUSIONS: Transplant
      recipients with unsuspected gallstones were found to have a high incidence of
      acute biliary complications. Urgent biliary surgery carried significant morbidity
      and mortality in these immunosuppressed patients and appeared to increase the
      risk of graft failure as well. A policy of screening gallbladder ultrasound and
      pretransplant laparoscopic cholecystectomy seems to reduce these concerns and is
      recommended for all transplant candidates.

PMID- 7817998
TI  - Activation of intestinal Na-K-2Cl cotransport by 5'-AMP requires F-actin
      remodeling.
AB  - BACKGROUND: Although cyclic adenosine monophosphate (cAMP)-dependent intestinal
      chloride ion (Cl-) secretion is regulated primarily at the level of apical Cl-
      channels, cAMP also elicits basolateral microfilament remodeling and activates
      basolateral sodium-potassium-2 chloride (Na-K-2Cl) cotransport. Without these
      additional events, secretion is inhibited. However, it is unclear whether
      microfilament-dependent activation of Na-K-2Cl cotransport is a direct effect of
      cAMP or a secondary response to the opening of apical Cl- channels. METHODS:
      Using the human intestinal epithelial cell line T84, we examined Cl- secretion
      elicited by 5'-adenosine monophosphate (5'-AMP), a novel agonist that activates
      apical Cl- channels without elevation of intracellular cAMP. RESULTS: 5'-AMP was
      found to activate basolateral Na-K-2Cl cotransport, but such regulation was
      abolished by the actin stabilizer, phalloidin. CONCLUSIONS: Basolateral Na-K-2Cl
      cotransport appears to be regulated, at least in part, as an indirect response to
      activation of apical Cl- channels, a pathway of regulation which may require
      cytoskeletal remodeling.

PMID- 7817999
TI  - Analyses of protein kinase C isoform expression in a colorectal cancer liver
      metastasis model.
AB  - BACKGROUND: Protein kinase C (PKC), centrally involved in signal transduction,
      has been implicated in colorectal carcinogenesis. The purpose of this study was
      to identify specific PKC isoform alterations associated with colorectal cancer
      metastases to the liver in an orthotopic transplantation nude mouse model.
      MATERIALS AND METHODS: Solid subcutaneous tumors from colorectal cancer cell
      lines were established in dorsal sites of nude mice (3 mice per cell line) by
      subcutaneous injection of 10(7) cells (> 90% viable). Orthotopic transplantation
      cecal tumors, representative of each passage (S1-5) were examined for specific
      PKC isoform messenger ribonucleic acid (mRNA) expression. In addition, a cell
      line representative of passage S5 was established, characterized by light and
      electron microscopy, karyotype, clonogenicity, doubling time, and assayed for
      total PKC activity and PKC isoform mRNA expression. RESULTS: After the fifth (S5)
      sequential orthotopic transplantation passage of the human colorectal cancer cell
      line, SW620, a highly metastatic clone was obtained. Relative to parental cells,
      metastatic SW620-S5 cells were less differentiated and demonstrated many more
      chromosomal abnormalities and lower clonogenicity. Total PKC activity was
      elevated in metastatic cells. In addition, specific PKC isoform mRNA alterations
      were noted: PKC-n (L) was abundantly expressed in the metastatic clone but absent
      from the parental cell line; PKC-alpha, delta and theta expression increased with
      serial orthotopic transplantation passages; PKC-delta remained unchanged, while
      PKC-beta was absent. CONCLUSIONS: Metastases-specific PKC isoform alterations may
      serve as novel markers of metastases and treatment targets via specific PKC
      isoform modulation.

PMID- 7818000
TI  - Randomized trial of duodenum-preserving pancreatic head resection versus pylorus
      preserving Whipple in chronic pancreatitis.
AB  - BACKGROUND: In about 30% of patients, chronic pancreatitis leads to an
      inflammatory enlargement of the pancreatic head with subsequent obstruction of
      the pancreatic duct, common bile duct, and duodenum. METHODS: In a prospective,
      randomized controlled trial, we compared duodenum-preserving pancreatic head
      resection (DPPHR) with pylorus-preserving Whipple (PPW) operation to define the
      advantages of each operation with regard to (1) postoperative complications, (2)
      glucose tolerance and induction of diabetes mellitus, and (3) postoperative pain
      and quality of life up to 6 months after operation for chronic pancreatitis.
      RESULTS: The two study groups of 20 patients were both well balanced with regard
      to sex, age, history of chronic pancreatitis, and indication for surgery.
      Postoperative mortality was zero. After duodenum-preserving and pylorus
      preserving resection, morbidity was 15% and 20%, respectively. After 6 months,
      patients who underwent the duodenum-preserving resection had less pain, greater
      weight gain, a better glucose tolerance, and a higher insulin secretion capacity.
      CONCLUSION: The DPPHR compares favorably with the standard PPW operation and
      should be considered as an alternative procedure in the treatment of chronic
      pancreatitis.

PMID- 7818001
TI  - A pilot study of preoperative chemoradiation for patients with localized
      adenocarcinoma of the pancreas.
AB  - BACKGROUND: We hypothesized that delivering adjuvant radiotherapy (RT)
      preoperatively with chemotherapy might enhance local control of the cancer and
      patient tolerance for the intervention. METHODS: Thirty-four patients with
      localized pancreatic cancer (24 head, 8 head and body, 2 body and tail) were
      treated during the past 6 years with an intramural protocol consisting of 5
      fluorouracil (1,000 mg/m2 on days 2 to 5 and 29 to 32) and mitomycin-C (10 mg/m2
      on day 2) given with preoperative external beam RT (median 5,040 cGy). Nine
      patients did not have surgery: 1 refused, 1 died of cholangitis, and 7 were noted
      to have distant (5) or unresectable local cancer (2) after RT. Of the 25 patients
      who underwent celiotomy, 11 had liver (8) or peritoneal (3) metastases and 3 had
      palliative pancreatectomies (2 with liver metastasectomy and 1 with hepatic
      artery and portal vein replacement). The remaining 11 patients (44% of the cohort
      with surgery, 32% of all patients) had potentially curative (PC) resections (5
      total pancreatectomy, 5 Whipple, 1 distal pancreatectomy). Median tumor diameter
      by computed tomographic scan was 3.75 cm (range 3 to 5) for the 11 patients who
      received PC resections and 4.5 cm (range 3 to 7.5) for all patients. Of the 11
      patients with PC resections, 8 had evidence of superior mesenteric, portal or
      splenic venous involvement and 4 had been deemed unresectable at previous
      celiotomies. RESULTS: One patient developed respiratory failure and one died
      postoperatively, yielding a 9% rate of major morbidity and mortality. Median
      follow-up of the surviving patients with curative resection is 33 months (range
      14 to 70). Their median survival from the time of tissue diagnosis is 45 months
      with a median disease-free survival of 27 months. The product limit estimate of 5
      year survival is 40% (95% confidence bounds +29%, -30%). One patient had a
      microscopically positive resection margin, which was a falsely negative frozen
      section margin at the pancreatic neck. Two patients had positive regional lymph
      nodes. Five patients have been diagnosed with recurrent cancer. Only 1 has had a
      local/regional component to the recurrence. CONCLUSIONS: Preoperative RT and
      chemotherapy followed by resection is well tolerated and safe for patients with
      locally advanced pancreatic cancer. This approach provides tumor free resection
      margins and offers prolonged survival to patients with truly localized pancreatic
      cancer.

PMID- 7818002
TI  - Epidural analgesia shortens postoperative ileus after ileal pouch-anal canal
      anastomosis.
AB  - PURPOSE: A retrospective study was conducted to determine whether epidural
      analgesia would speed recovery from postoperative ileus in patients undergoing
      ileal pouch-anal canal anastomosis. METHODS: Among 85 patients who underwent
      proctocolectomy with ileal pouch-anal canal anastomosis at the Mayo Medical
      Center between January 1, 1991 and October 31, 1992, 44 were treated for
      postoperative pain with continuous infusion of epidural fentanyl citrate
      supplemented by intravenous morphine on request, while 41 controls were given
      only systemic morphine sulfate as needed. RESULTS: The patients in the two groups
      were matched and similar with regard to preoperative and operative risk factors
      and postoperative morbidity. No operative mortality occurred. Epidural fentanyl
      analgesia resulted in less need for nasogastric suction and intravenous fluids,
      more rapid discharge of fecal content, more rapid return to oral intake, and
      shorter hospitalization. CONCLUSION: Epidural analgesia with fentanyl citrate
      shortened postoperative ileus after proctocolectomy and ileal pouch-anal canal
      anastomosis.

PMID- 7818003
TI  - Preliminary results of a prospective randomized trial of laparoscopic onlay
      versus conventional inguinal herniorrhaphy.
AB  - BACKGROUND: To compare laparoscopic onlay hernia repair with conventional
      surgery, 61 patients were randomized to either open or laparoscopic surgery.
      METHODS: Traditional repairs were done according to the surgeons' preference.
      Laparoscopic repairs utilized a modified onlay technique with a meshed prototype
      prosthesis. RESULTS: Mean operative time was 62.5 minutes for the laparoscopic
      group and 80.9 minutes for the open group. Each group had five complications.
      There were two conversions from laparoscopic to open surgery. Individuals
      undergoing laparoscopic surgery reported a mean intake of 5 doses of an oral
      narcotic analgesic versus 16 doses in the open group. Return to normal activity
      (nonstrenuous) was 7.5 days in the laparoscopic group and 18.5 days in the open
      group. After a mean follow-up of 8 months (range 1 to 14), there have been two
      recurrences in the open group and one in the laparoscopic group. CONCLUSION:
      Laparoscopic onlay inguinal herniorrhaphy is a viable alternative for those who
      prefer a minimally invasive treatment for this disease.

PMID- 7818004
TI  - Whither minimal access surgery: tribulations and expectations.

PMID- 7818005
TI  - A multicenter, placebo-controlled, randomized, double-blind, prospective trial of
      prophylactic ursodiol for the prevention of gallstone formation following gastric
      bypass-induced rapid weight loss.
AB  - BACKGROUND: Previous studies have documented a high incidence of gallstone
      formation following gastric-bypass (GBP)-induced rapid weight loss in morbidly
      obese patients. This study was designed to determine if a 6-month regimen of
      prophylactic ursodiol might prevent the development of gallstones. METHODS: A
      multicenter, randomized, double-blind, prospective trial evaluated 3 oral doses
      of ursodiol: 300, 600, and 1,200 mg versus placebo beginning within 10 days after
      surgery and continuing for 6 months or until gallstone development, for patients
      with a body mass index (BMI) > or = 40 kg/m2. All patients had normal
      intraoperative gallbladder sonography. Transabdominal sonography was obtained at
      2, 4, and 6 months following surgery, or until gallstone formation. RESULTS: Of
      233 patients with at least one postoperative sonogram, 56 were randomized to
      placebo, 53 to 300 mg ursodiol, 61 to 600 mg ursodiol, and 63 to 1,200 mg
      ursodiol. Preoperative age, sex, race, weight, BMI, and postoperative weight loss
      were not significantly different between groups. Gallstone formation occurred at
      6 months in 32%, 13%, 2%, and 6% of the patients on the respective doses.
      Gallstones were significantly (P < 0.001) less frequent with ursodiol 600 and
      1,200 mg than with placebo. CONCLUSION: A daily dose of 600 mg ursodiol is
      effective prophylaxis for gallstone formation following GBP-induced rapid weight
      loss.

PMID- 7818007
TI  - [Anesthesia in surgery for malformative and degenerative cervical spine].
AB  - Anaesthesia in patients with malformative and degenerative abnormalities of
      cervical spine poses a number of specific problems. A crucial point is the
      indispensable evaluation and observation before and during anaesthesia.
      Somatosensory evoked potentials being used to monitor nervous system pathways at
      risk during surgical procedures the effect of anaesthetic agents on these
      parameters are to be well known. Some pathologies are liable to per and
      postoperative specific risks breeding complications.

PMID- 7818006
TI  - Does duodenal juice reflux into the esophagus of patients with complicated GERD?
      Evaluation of a fiberoptic sensor for bilirubin.
AB  - BACKGROUND: It is controversial whether duodenal juice can damage esophageal
      mucosa in patients with gastroesophageal reflux disease (GERD). The issue remains
      unresolved partly because of difficulties in detecting the presence of duodenal
      juice in the lower esophagus. OBJECTIVES AND METHODS: This study utilized an in
      vitro portable spectrophotometer with a fiberoptic probe capable of detecting
      bile as a marker of duodenal juice. Absorbance/concentration curves were
      established with known bilirubin concentrations at pH 1.4 and pH 7.7. Esophageal
      pH and bilirubin absorbance were monitored in vivo over a 24-hour period in 20
      healthy volunteers to determine the absorbance threshold for clinical use. The
      study population consisted of 21 patients with GERD. Four had no mucosal injury,
      5 erosive esophagitis, and 12 Barrett's esophagus. RESULTS: The correlation
      between absorbance and bilirubin concentration was 0.98 and 0.99 for acid and
      alkaline environments, but bilirubin absorbance was 35% less in an acid
      environment. Using an absorbance threshold of 0.14, patients with GERD taken in
      toto had elevated esophageal exposure to bilirubin. No difference was observed in
      bilirubin exposure between reflux patients without mucosal injury and controls.
      Highest exposure occurred in patients with Barrett's esophagus. An important
      observation was that esophageal bilirubin exposure frequently occurred during
      periods when the esophageal pH was in the normal range. CONCLUSIONS: The
      fiberoptic probe accurately detects esophageal bilirubin as a marker of duodenal
      juice. Esophageal exposure to bilirubin is uncommon in normal subjects. Patients
      with erosive esophagitis and Barrett's metaplasia have increased esophageal
      exposure to duodenal juice compared to normal subjects. Reflux of duodenal juice
      into the esophagus can occur when the esophageal pH is within its normal range
      and is undetectable by pH monitoring alone.

PMID- 7818008
TI  - [Spinal cord diseases and neurological involvement: the clinician's point of
      view].

PMID- 7818009
TI  - [Trans-oral approach. Technique and indications].
AB  - The trans-oral approach is a well codified and classical technique in
      neurosurgery. When correctly performed, this procedure gives excellent results in
      selected indications, such as: mechanical decompression of ondotoidal vicious
      callus and more particularly, malformations of the craniovertebral function. This
      approach is also used for extirpation of C1, C2 and inferior clivus tumors. The
      complications of this technique are mainly septic, and must be prevented by
      appropriate pre and post-operative nursing.

PMID- 7818010
TI  - [Techniques for intubation when head and neck cannot be moved].
AB  - The inability to extend the head may be due to a blocked cervical spine or to any
      cervical instability imposing to maintain the head straight. Exposure of the
      glottis during intubation may be difficult and can be ameliorated by a stable
      general anesthesia, some pressure on the larynx and by charging the epiglottis.
      When mouth aperture is superior to 40 mm, a lighted stylet, a laryngoscope with a
      prism, a fiberoptic laryngoscope (Bullard) or the PCV laryngoscope represent a
      possible alternative to the Mac Intosh laryngoscope. If mouth aperture is
      superior to 20 mm but inferior to 40 mm, a ENT or PCV laryngoscope or a
      fiberoptic intubation are recommended. One should remember that the intubation is
      easier if the diameter of the ET tube is small. If the mouth aperture is inferior
      to 20 mm, nasal intubation (if intubation is indicated) is mandatory using
      fiberoptic intubation or a retrograde technique or even nasal blind intubation.
      In case of failure of intubation in a hypoxic patient, the anterior percutaneous
      route should always be kept in mind and transtracheal ventilation should be ready
      in case of failure, or even tracheotomy.

PMID- 7818011
TI  - [Anesthetic problems and postoperative care in the surgery for scoliosis].
AB  - Scoliosis surgery in the adolescent is prolonged, painful and haemorrhagic. There
      are neurological risks and surveillance of the medulla is necessary throughout
      surgery. An anterior (Dwyer, Zielke) or posterior (Harrington, Cotrel-Dubousset,
      Luque) approach to the spinal column cas used. Surgery using a posterior approach
      is the more haemorrhagic. The haemorrhage is increased by poor positioning of the
      patient, by the duration of surgery and by taking the bone graft. Constant care
      should be given to blood economy, using controlled hypotension, haemodilution and
      peroperative autotransfusion of lost blood (Cell-Saver). The anaesthetic should
      provide excellent analgesic effects and must be compatible with regain of
      consciousness during surgery and/or or the use of evoked potential techniques.
      Complications at that time are those of the circulation and those of neurological
      origin and linked with hypothermia. In the presence of haemorrhage, the
      maintenance of total blood volume is difficult when there is cardiopathy
      (myopathy). Neurological complications should be detected sufficiently early for
      them to be reversible (sensori-motor evoked potentials and/or "wake-up test").
      Hypothermia is constant and requires the systematic use of a heated mattress, a
      heated humidifier and the heating of infusions. The postoperative complications
      are respiratory in origin and are especially associated with neuro-muscular
      disease (postoperative artificial ventilation). The per- and postoperative
      difficulties demonstrate the importance of the preoperative examination and of
      the preparation of the operation (respiratory preparation). Finally, staged
      autotransfusion should be used, when possible, and should be part of the
      techniques of blood economy in a true transfusion strategy.

PMID- 7818012
TI  - [Lumbar disk herniation with surgical option: general versus local anesthesia.
      Round table].
AB  - Lumbar disc hernia is a frequent pathology whose treatment remains essentially
      surgical. The type of anesthesia can be general anesthesia with intubation and
      controlled ventilation, both mandatory due to the position, peridural or spinal
      anesthesia. The usual position is knee-chest position which impairs circulation
      and ventilation if some precaution are not taken. Spinal anesthesia has been
      chosen in more than 40% of the patients by Lille CHU Team. This choice is
      justified by the important level of satisfaction of the patients and the absence
      of complications due to the anesthesia in a series of 1871 consecutive spinal
      anesthesia for lumbar disc surgery.

PMID- 7818013
TI  - [Prone position and operative posture in neurosurgery].
AB  - The most satisfactory method of prone positioning for the posterior approach to
      the spine and posterior fossa has been influenced by the necessity of providing
      good operating condition: prone position without abdominal and thoracic
      compression with a patient's head in the neutral position. Communication between
      the cava veins and the vertebral venous plexus explain that induce positioning
      can produce an excessive venous intraoperative bleeding with decreased surgical
      visibility. Furthermore venous return to the heart decreased resulting in some
      degree of impaired cardiac output. Hemodynamic disturbances of cerebral or spinal
      cord bloods flows can occurred.

PMID- 7818014
TI  - [Evaluation of plasma levels of catecholamines, prolactin and cortisol during
      total intravenous anesthesia with propofol in the surgery of the lumbar spine].

PMID- 7818015
TI  - [Postoperative analgesia after surgical treatment of disk herniation].

PMID- 7818016
TI  - [Vascular obstruction of the duodenum. Apropos of 2 cases complicating the
      surgical treatment of scoliosis. Review of the literature].

PMID- 7818017
TI  - [Results of surgical treatment of scoliosis by Harrington's procedure:
      neurological complications and reliability of intraoperative monitoring of the H
      reflex].

PMID- 7818018
TI  - [Changes in thoracopulmonary compliance in normal and obese subjects in prone
      position].

PMID- 7818019
TI  - [Hemodynamic effects of genu-pectoral position during the surgery of lumbar disk
      herniation: spinal anesthesia versus general anesthesia].
AB  - Spinal anesthesia (SA) for lumbar disk surgery in the genu-pectoral position (GP)
      has been proposed as an alternative to general anesthesia (GA). This study
      compares the haemodynamic effects of GP in two groups of patients undergoing
      either SA (n = 43) or GA (n = 40). Mean arterial pressure (MAP) and heart rate
      (HR) were recorded before and after GP. MAP and HR were significantly lower in
      the GA group after GP. We conclude that SA during GP for lumbar disk surgery is
      haemodynamically well tolerated.

PMID- 7818020
TI  - [Right ventricular function and postural changes during surgery of the lumbar
      spine].
AB  - The aim of the study was to assess the effects of the sitting prone position on
      right ventricular function in a group of patients requiring low back surgery with
      using of right heart catheterization with a low fast response thermodilution
      technique. This posture involves moderated hemodynamic effects. A discrete right
      ventricle impairment characterised by a decreased compliance was observed and may
      be due to a moderate compression by the sternum and was improved by fluid
      challenge. Thus, the sitting prone position appears a safe position.

PMID- 7818021
TI  - [Changes in systolic pressure and posture in the surgery of the lumbar spine].
AB  - Anesthetized patients for lumbar disk surgery can be placed in prone or knee
      chest position which may adversely affect circulation. Augmentation of the delta
      down component of the systolic blood pressure variation in ventilated patient is
      a sensitive indicator of intra operative hypovolemia. According to results,
      cardiac filling pressure is more affected in the knee chest position than in
      prone position. Preload state variation between the two positions, evaluated with
      albumin fluid challenge, seems to be more important than 500 ml.

PMID- 7818022
TI  - [Malformative and degenerative diseases of the cervical spine: preoperative
      evaluation].
AB  - Malformative or degenerative abnormalities of the cranio-cervical joint which are
      the most frequently encountered in neurosurgery concern the occipital bone, the
      atlantoaxial joint and the surrounding nervous or vascular structures. These
      pathologies may have an acquired or congenital origin. In the last eventuality,
      they are frequently associated with other malformative disorders involving the
      vertebral column, the thorax, the kidneys or the heart. The clinical picture is
      various and many systems can be affected. Therefore, preoperative assessment of
      patients implies a multifactorial evaluation. The anesthesiologist should refer
      to the following check list: examination of the neck and cervical spine,
      neurological status, evaluation of associated diseases, pulmonary and cardiac
      function tests, airways permeability and conditions of endotracheal intubation.

PMID- 7818023
TI  - Seizures, brain damage and brain development.
AB  - Recent evidence suggests that hippocampal damage can be both the result of
      seizure activity and the cause of further chronic epilepsy. A review of current
      models of status epilepticus-induced brain damage reveals that excitotoxic
      mechanisms probably mediate the lesions in most brain regions. NMDA receptors
      appear to play a dominant role, although non-NMDA glutamate receptors are
      important in several specific neuronal populations. In the immature brain, a
      number of unique metabolic features determine a different set of vulnerabilities,
      resulting in a brain which is more resistant than the adult's to certain
      mechanisms of brain damage, but quite vulnerable to others. The inhibition of
      growth by severe seizure activity has implications for the developing brain that
      have not yet been fully explored. The mechanisms by which seizure-induced
      hippocampal lesions cause chronic epilepsy have been explored in several recent
      animal models. A rearrangement of hippocampal circuits may result from death of
      selected populations of inhibitory neurons, or from misdirected regeneration by
      excitatory neurons. It could lead to chronic epilepsy through loss of normal
      inhibition, through sprouting of new excitatory connections, through conservation
      of excitatory connections which in a healthy brain would be pruned during
      development, or through facilitation of kindling by one of these mechanisms.
      These recent results are beginning to reconcile the pathology seen in human
      hippocampi ablated for intractable epilepsy with that observed in experimental
      animals, and offer the promise of even greater advances in the future. They
      suggest a mechanism for Gower's dictum that "seizures beget seizures" and
      highlight the importance of the interneurons of the dentate gyrus in
      epileptogenesis.

PMID- 7818024
TI  - Aminophylline exhibits convulsant action in rats during ontogenesis.
AB  - Aminophylline-induced seizures were studied in 166 male albino rats in five age
      groups--7, 12, 18, 25 and 90 days old. Aminophylline injected in doses from 150
      350 mg/kg i.p. elicited both minimal, clonic and major, i.e. generalized tonic
      clonic seizures during the 60-min observation period. The pattern of minimal
      seizures did not change during development; major seizures exhibited changes in
      proportion to their three phases--running, tonic and clonic phases. Dependence on
      the dose of aminophylline was observed in the incidence of major seizures as well
      as in shortening of latencies of both types of seizures. More marked convulsant
      effects of aminophylline in 7-, 12- and 18-day-old rat pups than in older animals
      might be due to pharmacokinetic as well as pharmacodynamic factors.

PMID- 7818025
TI  - Left ventricular structure and function by echocardiography in congenital
      muscular dystrophy.
AB  - Cardiac involvement in congenital muscular dystrophy (CMD) has not previously
      been reported in the literature excepting Japanese ones. The purpose of this
      study was to investigate the probability of cardiac muscle involvement in 25
      patients with CMD. Left ventricular dimensions, wall thicknesses and function
      were investigated by M-mode and Doppler echocardiography in patients and healthy
      control subjects. The M-mode echocardiographic data were similar in the two
      groups. However, the left ventricular mass index in the study group was
      significantly lower than that of the control group. Left ventricular diastolic
      function also differed significantly when compared with that of the control
      group. Mild diastolic dysfunction of the left ventricle might precede
      manifestations of probable cardiac muscle involvement or subclinical cardiac
      involvement.

PMID- 7818026
TI  - The value of EEG in children with chronic headaches.
AB  - To establish the usefulness of electroencephalography (EEG) as a diagnostic tool
      in the evaluation of headaches in children, we retrospectively reviewed the
      records of all children referred to our outpatient neuropediatric clinic because
      of recurrent headaches. Of 312 children, 257 (82%) underwent EEG tracings: 143 of
      the children who had had EEG recordings were diagnosed as migraineurs. In 31
      (12%) of the children, the EEG revealed epileptic activity. The highest incidence
      of epileptic EEG activity was found amongst the children with very brief
      headaches. In 22 (8.6%) of the children, diffuse or focal slowing was detected.
      The group with migraine headache had a significantly higher incidence of slowing
      than the group with other types of headaches. There was no correlation between
      focal EEG abnormalities and brain radioimaging studies or clinical course. We
      conclude that despite the high incidence of epileptic abnormalities, the
      contribution of EEG to diagnosis and treatment in children with chronic headache
      is minimal, and should not be routinely prescribed in these children.

PMID- 7818027
TI  - Peculiar eosinophilic inclusions within astrocytes in a patient with malformed
      brain.
AB  - At autopsy, we observed eosinophilic inclusions within the astrocytic cytoplasm
      in areas of polymicrogyria and heterotopic gray matter in a 17-year-old female
      with severe mental retardation and physical handicaps who had died of respiratory
      failure. The inclusions stained with acid fuchsin, azocarmine, Holzer's stain and
      phosphotungstic acid hematoxylin (PTAH). They reacted with anti-S-100 protein
      antibody. The cytoplasm of the astrocytes containing the inclusions reacted with
      antibody to GFAP. The inclusions were amorphous masses that consisted of
      aggregated clusters of osmiophilic coarse granules about 30 nm in diameter. Some
      rough endoplasmic reticulum was observed on the inside and outside of the
      inclusions and in the cytoplasm of the astrocytes lacking such inclusions. We
      suggest that these inclusions resulted from an abnormality at or near the rough
      endoplasmic reticulum.

PMID- 7818028
TI  - Evaluation of patients with lactic acidosis using microphotometric mitochondrial
      enzyme assay in single muscle fibers.
AB  - Microphotometric enzyme assay in single muscle fibers was performed on two
      patients with lactic acidosis. Neither case showed ragged red fibers upon
      histochemical evaluation. Biochemical analysis of mitochondrial enzymes
      demonstrated low normal cytochrome c oxidase (COX) activity in Case 1 and
      deficient COX in Case 2. Quantitative single muscle fiber analysis in patients
      showed marked variation in COX activity in Case 1, reflecting mosaic distribution
      of fibers with near-normal COX activity and with defective COX activity. These
      data suggest that this microphotometric assay may be valuable for elucidating the
      significance of 'partial enzyme deficiency'. In addition, this assay method may
      be applied to needle biopsy specimens.

PMID- 7818029
TI  - Interictal EEG findings in two cases with 'double cortex' syndrome.
AB  - 'Double cortex' is a neuroblast migrational disorder characterized by a diffuse
      band of heterotopic grey matter between the lateral ventricles and cerebral
      cortex which may be normal or macrogyric. The authors report two girls with
      'double cortex' syndrome presenting intractable partial epilepsy and severe
      mental retardation. EEG data are analysed in detail because such patients
      presented a particular interictal EEG background activity, not only with very
      stable features during the different stages of vigilance, but also uninfluenced
      by seizure frequency or duration. The authors raise the possibility that a
      further in vivo diagnostic parameter for this syndrome has been identified.

PMID- 7818031
TI  - A correlated fluctuation of language and EEG abnormalities in a case of the
      Landau-Kleffner syndrome.
AB  - Despite growing interest in the Landau-Kleffner syndrome there have been few
      reports dealing with language disorders in recent years. The authors present a
      clinical case of a child with Landau-Kleffner syndrome focusing particularly on
      the relationship between language disorders and electroencephalographic
      abnormalities. The authors emphasize that the language disorders primarily affect
      the receptive sphere and that there seems to be a relationship between
      abnormalities during sleep with a deterioration in verbal comprehension.

PMID- 7818030
TI  - Short latency somatosensory evoked potentials and 99mTc-HMPAO SPECT in a case of
      flunarizine-effective alternating hemiplegia in infancy.
AB  - Short latency somatosensory evoked potentials (SSEPs) and 99mTc
      hexamethylpropylene amine oxime single photon emission computed tomography (99mTc
      HMPAO SPECT) were examined in a patient with alternating hemiplegia in infancy
      (AHI) before and after flunarizine treatment. The low amplitude and elongation of
      the latency time at the C'4 level of the interictal SSEPs before treatment were
      ameliorated by flunarizine administration. The cerebral hypoperfusion in the
      right hemisphere observed on 99mTc-HMPAO SPECT before treatment improved, as seen
      by normal and symmetrical imaging, after flunarizine treatment. These
      observations suggest that AHI is caused by a functional disturbance in the
      cerebral area contralateral to the hemiplegia, and that SSEPs and 99mTc-HMPAO
      SPECT are useful for evaluating functional disturbance in the contralateral
      motoneurons and the effect of flunarizine treatment in AHI patients.

PMID- 7818032
TI  - Different patterns of [18F]dopa uptake in siblings with hereditary dentato-rubro
      pallido-luysian atrophy.
AB  - Striatal glucose metabolism and [18F]dopa uptake were studied by positron
      emission tomography (PET) in two siblings with hereditary dentato-rubro-pallido
      luysian atrophy (HDRPLA). The regional cerebral metabolic rate of glucose showed
      marked decreases in the cerebellum and brainstem in both cases. The elder
      brother, who had trunk titubation and intention tremor of extremities, showed
      decreased [18F]dopa uptake in the striatum. On the other hand, the younger
      brother, who had spontaneous myoclonus of the right shoulder and flank, showed
      increased [18F]dopa uptake in the striatum. These findings suggested that the
      wide variety of clinical symptoms of HDRPLA observed within a single family is
      closely related to the various neuronal dysfunctions at the neurotransmitter
      level.

PMID- 7818033
TI  - [Ardystil syndrome. A new occupational disease].

PMID- 7818034
TI  - [Prognostic significance of p53 expression in gastric carcinoma].

PMID- 7818035
TI  - [MDMA (Ecstasy). A designer drug with high toxicity potential].

PMID- 7818036
TI  - [Life and works of Professor Matilla].

PMID- 7818037
TI  - [Academician Prof. Matilla].

PMID- 7818038
TI  - [Recovery of the right cerebral hemisphere].

PMID- 7818039
TI  - [Atypical glandular hyperplasia of the endometrium. Anatomo-clinical
      considerations].

PMID- 7818040
TI  - [Ethnobotany].

PMID- 7818041
TI  - [Primitive matrix and neural function].

PMID- 7818042
TI  - [Hypertrophic and dilated cardiopathy in the fetus: an experimental study].

PMID- 7818043
TI  - [Annotations for neuroepistemology].

PMID- 7818045
TI  - [Continuous intravascular blood gas analysis. Clinical evaluation of a new fiber
      optic monitor].
AB  - Continuous monitoring of blood gases and pH could add substantially to patient
      safety. During the last decade, efforts have been made to develop continuous
      optochemical blood gas sensors. The initial evaluation of such fibreoptic-based
      systems showed major patient-interface problems [11]. We evaluated a new intra
      arterial blood gas monitoring system (PB3300, Puritan-Bennett, Carlsbad CA) under
      routine clinical conditions. METHODS. After institutional review board approval
      and with written informed consent, 38 sensors were tested in 25 patients with
      acute respiratory failure (e.g., the acute respiratory distress syndrome,
      complications after lung transplantation). Two conventional bench-top blood gas
      analysers (ABL 520 and ABL 300, Radiometer, Copenhagen) served as criterion
      standards. The mean differences (bias) and standard deviations (SD) of the
      differences (precision) were calculated according to the method of Bland and
      Altman [2]. In addition, linear regression analysis and correlation coefficients
      were calculated. The quality of blood pressure tracings was assessed using a
      grading system. RESULTS. The median sensor lifetime was 81.3 h; 869 blood samples
      (median 14 per sensor) were analysed for the comparison of continuous and
      conventional blood gas analysis. The ranges for measured parameters were: pH:
      6.92 to 7.55; PCO2: 20 to 83 torr; PO2: 31 to 518 torr. The mean differences (SD)
      were: pH: -0.03 (0.03) or -0.4 (0.4)%; PCO2: -2.6 (4.1) torr or -6.9 (10.9)%;
      PO2: -3.4 (10.5) torr or -2.9 (7.0)%. The results of linear regression analysis
      and the correlation coefficients are depicted in Table 2. The mean grade of blood
      pressure tracings was satisfactory for the clinical setting. CONCLUSIONS. The
      continuous blood gas monitor is sufficiently accurate and precise for clinical
      use. Bias and precision are better than those known from former studies
      evaluating fibreoptic blood gas monitors under experimental conditions [7]. Cost
      effectiveness was not an issue of this study.

PMID- 7818044
TI  - [Perioperative endothelin, ACTH and cortisol plasma concentrations in coronary
      bypass patients].
AB  - STUDY OBJECTIVE: To follow up endothelin (ET), adrenocorticotropic hormone
      (ACTH), and cortisol levels in patients undergoing aortocoronary bypass grafting
      (CABG) and to determine whether these are extracted from plasma by the pulmonary
      circulation. DESIGN: Convenience sample trial. SETTING: University hospital.
      PATIENTS: Eight male routine CABG patients without appreciable concomitant
      disease. INTERVENTIONS: Patients were given anaesthesia in a strictly
      standardised manner using etomidate, flunitrazepam, fentanyl, and pancuronium.
      Nitroglycerin was administered prior to cardiopulmonary bypass (CPB) at 2 mg/h
      and dopamine as the only catecholamine starting from CPB weaning until the end of
      sampling at 3.5-5 micrograms/kg.min. Samples were drawn in rapid sequence from
      cannulated radial and a distal pulmonary arteries (Swan-Ganz catheter) at eight
      sampling times starting after induction of anaesthesia and catheter placement and
      finishing 22 h after the end of operation. MEASUREMENTS AND RESULTS: ET levels
      were determined by an ET-1, 2, 3-sensitive radioimmunoassay (RIA), ACTH and
      cortisol by commercially available RIA kits. There was significant (P = 0.032,
      linear regression analysis) correlation between ET and cortisol from pulmonary
      arterial samples. ET was significantly (P = 0.042, two-tailed Wilcoxon test)
      extracted by the pulmonary circulation after induction of anaesthesia. This
      pulmonary-systemic arterial difference nearly disappeared intraoperatively, but
      tended to be restored 22 h after the end of operation at an approximately twofold
      increased level. CONCLUSIONS: No interrelation between ET and the hypothalamic
      pituitary-adrenal axis could be established by the ET, ACTH, and cortisol plasma
      levels. However, the significant correlation between perioperative ET and
      cortisol lends further support to the hypothesis of ET release by cortisol from
      vascular smooth-muscle cells. There is a net pulmonary clearance of ET in
      patients prior to CABG that is lost intra- and early postoperatively, but tends
      to be restored on the 1st day thereafter at an increased level.

PMID- 7818046
TI  - [Postoperative warming therapy in the recovery room. A comparison of radiative
      and convective warmers].
AB  - Hypothermia (Tcore < 36 degrees C) can be observed in 60%-80% of all admissions
      to the post-anaesthetic recovery unit. Effective warming devices may accelerate
      rewarming, improve patient comfort, and suppress shivering thermogenesis. This
      study was designed to compare the efficiency of warming devices in extubated
      postoperative patients and their effect on postoperative oxygen uptake (VO2).
      METHODS. Thirty-five ASA I and II patients after laparoscopic hernioplastic
      repair with core temperatures < 36 degrees C were randomly assigned to either
      postoperative nursing under a radiant heater (group R, n = 11, Aragona Thermal
      Ceilings CTC X, Aragona Medical AB, Taby, Sweden), a forced air system (group L,
      n = 12, Bair Hugger, Augustine Medical Inc., Eden Prairie, Minnesota, USA), or a
      normal cotton hospital blanket (group K, n = 12). Anaesthesia was conducted
      totally intravenously with propofol, alfentanil, and vecuronium. Mean body
      temperature and total body heat were calculated from urinary bladder temperature
      and four subcutaneous temperature measurements. The rate of thermogenesis was
      calculated from continuous measurement of VO2 (Datex Deltatrac Metabolic Monitor,
      Datex Instrumentarium Corp., Helsinki, Finland). Heat balance was derived from
      the increase in total body heat minus body heat production. Heart rate and
      noninvasive blood pressure were measured by the Cardiocap (Datex Instrumentarium
      Corp., Helsinki, Finland). All data were transferred to an IBM-compatible
      computer at 60-s intervals. Measurements were stopped when core temperature
      reached 37 degrees C. The rate of change was calculated for each variable for the
      period 15 min after the beginning of rewarming to attainment of 37 degrees C.
      Data are presented as median, minima, and maxima (min<==>max); the Mann-Whitney U
      test was used to test for significance of group differences. RESULTS. All groups
      were comparable for body weight, height, age, and amount of postoperative
      infusions. Temperatures at admission were 35.2 (33.4<==>35.9), 34.7
      (34.3<==>35.8), and 35.4 (34.3<==>35.9) degrees C for groups R, B, and K,
      respectively. No significant differences in the rate of central rewarming could
      be found for these groups with 0.81 (0.41<==>1.32), 0.76 (0.40<==>1.07), and 0.70
      (0.37<==>1.13) degrees C/h (Fig. 1). The mean VO2 of 3.41 (3.07<==>3.73), 3.55
      (2.78<==>4.06), and 3.79 (2.51<==>7.00) ml/kg/min also did not differ
      significantly (Fig. 3). Significant differences between groups R and B [4.39
      (3.74<==>6.19) and 4.30 (3.46<==>6.67) ml/kg/min] and K [5.92 (3.79<==>10.64)
      ml/kg/min] were found for VO2 maxima during the course of investigation (Fig. 4).
      The heat balance revealed significant differences among treatment and control
      groups with -88 (-226<==>+30), -41 (-212<==>+12), and -191 (-265<==>-86) kJ/h for
      groups R, B, and K. We additionally calculated the heat balance as a quotient,
      which showed 0.70 (0.22<==>1.07), 0.86 (0.44<==>1.04), and 0.49 (0.31<==>0.79)
      for groups R, B, and K (Fig. 4). The mean rate-pressure product of all groups did
      not differ significantly during the period of investigation. CONCLUSIONS. Neither
      external heat supply by radiant heat nor by a forced warm air system
      significantly reduced rewarming time in extubated, awake patients. As measured by
      heat balance, both active treatments saved about 20% more body heat production
      than in the control group. Continuing peripheral vasoconstriction may be the
      reason for the low efficiency of heat transfer. Thermal treatment did reduce the
      peak load (max. VO2) on the oxygen transport systems, though shivering was
      treated by pethidine if it occurred. External rewarming did not reduce the
      average load (mean VO2). Thus, concerning the goal of accelerating rewarming, it
      appears more rational to prevent intraoperative heat loss. For a comparison of
      efficiency of different warming devices, postoperative extubated patients do not
      appear to be an ideal model for study.

PMID- 7818047
TI  - [Inverse fick's principle in comparison to measurements of oxygen consumption in
      respiratory gases. Does intrapulmonary oxygen uptake account for differences
      shown by different system methods?].
AB  - Automated measurements of respiratory gas exchange recently became available for
      the determination of oxygen uptake (VO2) in critically ill patients. Whereas
      these metabolic gas monitoring systems (MBM) are assumed to measure total body
      VO2, the reversed Fick method in principle excludes intrapulmonary VO2. Previous
      clinical reports comparing VO2 measured by the reversed Fick principle (VO2Fick)
      with VO2 measured by MBM (VO2MBM) found that VO2MBM was significantly greater
      than VO2Fick. It was suggested that these differences between methods represent
      VO2 of pulmonary and bronchial tissue, as intrapulmonary VO2 had been estimated
      to account for 15% of total body VO2 in dogs with experimental pneumonia. The
      objective of this study was to compare VO2Fick with VO2MBM in patients with and
      without pneumonia and to assess the reproducibility of both methods in critically
      ill patients. METHOD. With institutional approval nine critically ill patients
      with acute pneumonia were studied under controlled mechanical ventilation. The
      diagnosis of pneumonia was based on respective changes of chest X-rays, body
      temperature > 38 degrees C, and WBC counts > 12,000/mm3. Inspiratory oxygen
      fractions (FIO2) ranged from 0.3 to 0.6; all patients routinely received opioids
      and hypnotics. Complete muscle relaxation was achieved during the periods of
      measurement to avoid sudden changes in VO2 due to shivering or involuntary
      movements. Arterial and pulmonary-arterial blood samples were drawn
      simultaneously after aspiration of the sevenfold catheter dead space.
      Measurements of haemoglobin concentration (Hb), fractional oxygen saturation
      (SO2), and O2 partial pressure (PO2) were performed by use of a calibrated
      haemoximeter and blood gas analyser, respectively; 2 x 5 thermodilution
      measurements of cardiac output (CO) were spread randomly over the respiratory
      cycle for each determination of VO2Fick. To minimise systematic errors of CO
      measurements, the CO computer was calibrated in an extracorporeal flow model
      using an electromagnetic flowmeter. Calculations of VO2Fick were based on an
      oxygen binding capacity of 1.39 ml/g Hb. Simultaneous measurements of VO2MBM were
      obtained by use of a Datex Deltatrac MBM that had been validated in vitro with a
      gas dilution model of respiratory gas exchange. Calibration of the MBM was
      performed prior to each measurement. Gas supply of the respirator was provided by
      an external high-precision mixing device to reduce errors in VO2 measurements
      that may arise from short-term oscillations in FIO2. All patients with pneumonia
      were studied on three consecutive days; thus, measurements from 27 days could be
      analysed. On each day two sets of measurements were performed at an interval of
      60 min to assess the reproducibility of differences between methods. During each
      set of measurements duplicate blood samples were drawn twice, before and after
      thermodilution measurements of CO, to evaluate the short-term repeatability of
      VO2Fick. The beginning and the end of each set of measurements were marked in the
      computer record of the MBM to assess the respective repeatability of VO2MBM.
      Fifty control measurements were performed in ten patients undergoing major
      neurosurgical procedures. None of these patients exhibited signs of pulmonary
      infection. Except for the number of repeated measures, all VO2 measurements were
      obtained in the same way as in the study group. Descriptive statistical analysis
      was performed according to Bland and Altman; comparisons between methods were
      done by multivariate analysis of variance for repeated measures. RESULTS. Neither
      in the study group nor in the control group could a significant difference
      between methods be demonstrated. In patients with pneumonia the mean difference
      between methods (VO2Fick-VO2MBM) was 15.2 ml/min (4.2%); the double standard
      deviation of differences (2 SD) was 59.2 ml/min (19.2%).

PMID- 7818048
TI  - [Obstetric peridural anesthesia with sufentanil. Is it contraindicated?].
AB  - The advantages of the addition of low-dose sufentanil to local anaesthetics in
      epidural analgesia during labour (improvement of analgesia, reduction of total
      dose of local anaesthetic, reduction of rate of instrumental delivery outweigh)
      far the disadvantages (pruritus, sedation, potential maternal and neonatal
      respiratory depression). In over 8000 cases, the addition of incremental
      sufentanil (7.5 micrograms) up to 30 micrograms has not caused any negative
      effects on newborns, and hence, the addition of sufentanil is justified; it may
      even be indicated. Sufentanil has not yet been registered for epidural analgesia
      in Germany, in contrast to other countries. In considering whether this fact may
      prohibit its use, two aspects should be discussed: therapy and clinical
      experiments. The difference lies in the purpose rather than in the method of
      administration. Ethical and legal requirements for clinical tests are anchored in
      the declaration of Helsinki and the code of the medical profession. The legal
      background for therapy is represented in the proviso of the German Civil and
      Criminal Codes as well as the code of conduct on professional liability of the
      physician. Pain during labour is no absolute indication for the addition of
      sufentanil, but there are considerable arguments for its superiority in
      comparison to other standard procedures: the side effects and complications are
      very limited. Justification of this method is relatively easy in view of the fact
      that sufentanil has already been registered for peridural analgesia in obstetrics
      in many other countries. Last but not least, the patient must give informed
      consent before any procedure can be performed.

PMID- 7818049
TI  - [Undetected esophageal foreign body aspiration in a patient with seizures].
AB  - We report an oesophageal foreign body in a patient with a seizure disorder
      secondary to encephalitis disseminata who was transferred to our department of
      neurosurgery because of rising intracranial pressure. He presented with
      confusion, motor aphasia, and dysphagia. However, the diagnosis of increased
      intracranial pressure could not be confirmed clinically or by computed
      tomography. A routine chest X-ray film showed a dental prosthesis projecting on
      the area of the hypopharynx. Bronchoscopy and oesophagoscopy showed the denture
      to be lodged in the hypopharynx, but it was impossible to remove it
      endoscopically. Therefore, an oesophagopharyngotomy was performed and the foreign
      body extracted. The postoperative course was complicated by pneumonia, which
      responded well to antibiotic treatment. The patient made an otherwise uneventful
      recovery and was able to eat without difficulty.

PMID- 7818050
TI  - [Ultrasonic guided cannulation of the axillary vein in intensive care patients].
AB  - Cannulation of the axillary vein is claimed to be an effective and relatively
      safe access to the central venous (CV) system [2, 4, 5, 8]. However, anatomical
      landmarks recommended for venous location (Muskulus pectoralis minor, processus
      coracoideus) are probably hard to identify in the majority of intensive care
      (ICU) patients. This investigation evaluated unidirectional 8 MHz Doppler
      ultrasound (US) in locating the axillary vein. Success rates and complications of
      this CV access in ICU patients is analysed. METHODS. The experimental design was
      approved by the local ethical committee (RUB). In 50 patients from our ICU
      cannulation of the axillary vein was attempted; all were in need of a CV line.
      Other CV puncture sites (except for the subclavian vein) were associated with
      contraindications. Patients were placed in a 15 degrees Trendelenburg position
      (15 exceptions); the arm was abducted to 45 degrees [5, 8]. The course of the
      axillary vein was located by Doppler US and marked on the skin with a felt pen.
      Prior to puncture, US intensity was judged by a score ranging from 0 to 4. After
      skin desinfection, sterile draping, and local anaesthesia, puncture of the
      axillary vein was attempted. The puncture kit LeaderCath 11,515 (Vygon, Aachen,
      FRG) was used. When venous blood could be aspirated, the Seldinger guidewire was
      inserted and the definite catheter placed. The experimental design allowed up to
      ten punctures, slightly modified in angle and direction of the needle, if
      puncture of the axillary vein or guide-wire placement failed. The cannulation
      attempt was classified as unsuccessful in the following cases: malposition,
      axillary vein not encountered by the puncture needle, guide-wire placement
      unsuccessful, or if identification and cannulation of the vein lasted more than
      20 min. The puncture attempts were evaluated in respect to success rate, time,
      relation of US intensity to puncture attempts and CV pressure, complications, and
      malposition. RESULTS. Of the 50 attempted CV catheters, 43 were placed
      successfully. In 2 cases the axillary vein could not be encountered by the
      puncture needle. Guide-wire placement did not succeed in 4 patients. One catheter
      was malpositioned in the ipsilateral internal jugular vein. Four inadvertent
      punctures of the axillary artery remained without sequelae after compression. No
      further puncture-related complications were observed. With high US intensity
      score the number of puncture attempts necessary for successful vein cannulation
      was lower. On the other hand, complications and puncture failure seemed to be
      more frequent in patients with lower US intensity scores. DISCUSSION. CV access
      via the axillary vein had a satisfying success rate (43/50) and proved to be a
      safe procedure in our ICU patients despite higher risk factors compared to a
      healthy population. Although ethical reasons did not allow a randomised
      comparison with the standard technique, location of the axillary vein by Doppler
      US is likely to improve cannulation results and reduce complications induced by
      "blind" needle probing. With a low US intensity score, the rate of successful
      punctures is lower and complication rates increase. In some patients, e.g., those
      with extended tumour operations involving the head and neck, CV access via the
      axillary vein may be of high clinical value.

PMID- 7818051
TI  - [The effect of perioperative transfusions in prognosis of tumor patients?].

PMID- 7818052
TI  - [Therapy of post-zoster neuralgia].

PMID- 7818053
TI  - [Ventilation-perfusion ratios].
AB  - Knowledge of normal and impaired pulmonary gas exchange is essential to the
      anaesthesiologist. Analysis of an arterial blood sample allows evaluation of
      whether or not pulmonary gas exchange is normal. For this purpose comparison with
      the oxygenation index or the alveolar-arterial PO2 difference is helpful.
      Pathological changes of these variables are mainly caused by ventilation
      perfusion (VA/Q) mismatch. In daily practice, venous admixture or intrapulmonary
      shunt can be calculated using arterial and mixed-venous blood. By analysing
      arterial and expired PCO2, dead-space ventilation can be determined, but extended
      analyses of VA/Q distribution are not possible in daily practice. However,
      knowledge of the principles of typical disturbances of pulmonary gas exchange in
      acute and chronic lung disease allows the use of therapeutic strategies based on
      the pathophysiological changes.

PMID- 7818054
TI  - The De Ford Somnoform inhaler.

PMID- 7818055
TI  - Pharmacokinetics of bupivacaine enantiomers during interpleural infusion.
AB  - Interpleural infusions (24 hr) were given to 14 adults (29-81 yr) having surgery
      via right subcostal incisions. Patient-controlled analgesia with morphine was
      also available for 72 hours following surgery. An infusion of 0.25% bupivacaine
      with adrenaline 1/400,000 was commenced at 0.1 ml/kg/hr at the conclusion of
      surgery after an initial 20 ml bolus. The 24 hr cumulative morphine dose
      increased by 62% (P < 0.01) on the second postoperative day after the bupivacaine
      infusion was ceased, but the pain score did not change. There was no clinical
      evidence of bupivacaine toxicity although the maximum bupivacaine concentration
      ranged from 0.74-6.52 mg/l, mean 2.90 (SEM 0.44) mg/l and vascular uptake was
      rapid in two patients. The concentration of S-bupivacaine was consistently
      greater than R-bupivacaine (P < 0.05) and total body clearance was less. The
      unbound bupivacaine fraction also changed from 3.6% (SEM 0.6) at the start of the
      infusion to 2.0% (SEM 0.3) at 24 hr (P < 0.005). The total body clearance of each
      enantiomer was reduced during the 24 hours (P < 0.001). No relationship between
      pharmacokinetic parameters and weight, age or sex was found (P > 0.25 for each).
      Variation between patients was reduced when parameters were estimated for the
      free (unbound) bupivacaine (P < 0.001).

PMID- 7818057
TI  - Premedication with oral midazolam in children--an assessment of psychomotor
      function, anxiolysis, sedation and pharmacokinetics.
AB  - We studied 30 children, aged 4 to 12 years, undergoing elective circumcision,
      premedicated with midazolam 0.5 mg.kg-1 and atropine 0.02 mg.kg-1 by mouth. A
      modified postbox test and the coding component of the Wechsler intelligence scale
      (WISC-R) was used to assess the preoperative effect of premedication on
      psychomotor function. Mood and sedation were also scored and related to serum
      midazolam concentrations. The children showed a significant decline in
      psychomotor performance 30 and 60 minutes after premedication when compared with
      their best unmedicated performance recorded the previous evening. This decline in
      psychomotor performance was only weakly associated with serum midazolam
      concentrations (r = 0.1). The postbox toy ratio is a suitable measurement of
      psychomotor performance in children because of its simplicity and ease of use in
      the clinical environment, although it may suffer the "test-retest" limitations of
      similar types of assessment. The sedative and anxiolytic effects of midazolam
      provide a quiet environment for a smooth induction of anaesthesia.

PMID- 7818056
TI  - Thrombelastographic patterns following abdominal aortic surgery.
AB  - Postoperative changes in thrombelastographic patterns were studied in thirty
      patients undergoing elective abdominal aortic bypass surgery. Native whole blood
      thrombelastography was performed preoperatively and on days 1, 2, and 3
      postoperatively. The thrombelastographic changes included a decrease in r on day
      one (P < 0.0001), with concurrent increases in alpha (P < 0.0001) and MA (P <
      0.001). On days 2 and 3 there were further increases in MA (P < 0.0001). These
      changes indicate enhanced procoagulant activity and progressive increases in
      maximum clot strength. The results confirm that hypercoagulability occurs in
      whole blood following abdominal aortic bypass surgery. Further studies are
      warranted to determine whether modification of postoperative hypercoagulability
      reduces the incidence of thrombotic complications in this group of patients.

PMID- 7818058
TI  - A comparison of three induction agents in paediatric anaesthesia--cardiovascular
      effects and recovery.
AB  - We studied 30 children undergoing circumcision randomly allocated to receive
      either thiopentone 4 mg.kg-1, propofol 2.5 mg.kg-1 or midazolam 0.5 mg.kg-1 (n =
      10) IV over 30 seconds at induction of anaesthesia. Blood pressure and pulse rate
      during the first 15 minutes of induction were recorded by a Finapres 2300e and a
      Cardiocap CM-104, and changes from preinduction baseline compared between the
      three induction agents and the two recording instruments. Postoperatively, blood
      levels of the induction agents were measured and recovery from anaesthesia was
      assessed by clinical criteria, mood and sedation scores and psychomotor
      performance. The Cardiocap data revealed no statistically significant
      haemodynamic differences between the three induction agents. Finapres data
      demonstrated that propofol caused a greater decrease in mean arterial pressure
      when compared to thiopentone at one minute (P = 0.01) and the MAP remained
      significantly lower than midazolam at five minutes (P = 0.02), illustrating an
      advantage of continuous over intermittent non-invasive blood pressure monitoring.
      The midazolam group took longer to identify themselves compared to both the
      propofol (P = 0.005) and the thiopentone groups (P = 0.02), but there was no
      difference in the groups in time to eye-opening. Psychomotor performance on
      awakening was significantly worse in the midazolam group compared to the propofol
      (P < 0.03) and thiopentone groups (P < 0.02). Most children had recovered to 80%
      of their best, practised, unmedicated, preoperative performance four hours after
      awakening, irrespective of the induction agent administered. Drug blood levels
      correlated weakly with both methods of psychomotor assessment (r > or = 0.6). Of
      the three induction agents, thiopentone caused the least haemodynamic
      perturbation on induction, and anaesthesia induced with midazolam caused the
      greatest psychomotor impairment on awakening. Within one hour patients in all
      drug groups were equally awake, co-operative and co-ordinated.

PMID- 7818059
TI  - Adverse incident reporting in intensive care.
AB  - This prospective, observational, anonymous incident reporting study aimed to
      identify and correct factors leading to reduced patient safety in intensive care.
      An incident was any event which caused or had the potential to cause harm to the
      patient, but included problems in policy or procedure. Reports were discussed at
      monthly meetings. Of 390 incidents, 106 occasioned "actual" harm and 284
      "potential" harm. There was one death, 86 severe complications and 88
      complications of minor severity. Most were transient but the effects of 24 lasted
      up to a week. Most incidents affected cardiovascular and respiratory systems.
      Incident categories involved drugs, equipment, management or procedures. Incident
      causes were knowledge-based, rule-based, technical, slip/lapse, no error or
      unclassifiable. The study has identified some human and equipment performance
      problems in our intensive care unit. Correction of these should lead to a
      reduction in the future incidence of those events and hence an increased level of
      patient safety.

PMID- 7818060
TI  - Referral of surgical patients to an anaesthetic clinic: a decision-making
      analysis.
AB  - Effective utilization of an anaesthetic clinic depends on appropriate referral of
      high-risk surgical patients. The decision-making behaviour of anaesthetists and
      nurses was examined to identify factors that influence the referral of patients
      to an outpatient anaesthetic clinic. Eleven consultant anaesthetists, seven
      anaesthetic trainees and sixteen nurses working in anaesthetic areas estimated
      the likelihood that they would refer patients for each of the 30 scenarios
      presented. The relative importance of each factor influencing the decision to
      refer as determined by the 34 participants were: type of procedure (22%), co
      morbidities (18%), fitness (13%), history of anaesthetic problems (12%),
      medications (11%), age (10%), obesity (8%) and anxiety (6%). Indicative risk
      factors identified were aged 65 years or over, unable to climb more than two
      flights of stairs, presence of significant medical problems, gross obesity,
      history of anaesthetic problems, taking regular medications, scheduled for major
      surgery and expressed anxiety about the anaesthetic. There were large variations
      in the decision-making behaviour among health professional groups.

PMID- 7818061
TI  - Propofol injection pain: comparing the addition of lignocaine or metoclopramide.
AB  - Lignocaine has been shown to reduce the incidence of pain on injection of
      propofol. Metoclopramide, a weak local anaesthetic and commonly used antiemetic,
      was combined with propofol and the mixture compared, in a prospective, randomized
      trial, with a lignocaine-propofol combination. The incidence of injection pain
      was similar in both groups, as were recovery times and incidence of vomiting. The
      metoclopramide-propofol group experienced a lower incidence of nausea. One
      patient in the metoclopramide-propofol group had a minor extrapyramidal reaction.
      No adverse local or haemodynamic effects were seen.

PMID- 7818062
TI  - External abdominal aortic compression: a study of a resuscitation manoeuvre for
      postpartum haemorrhage.
AB  - External aortic compression is an emergency manoeuvre proposed to reduce
      postpartum haemorrhage and permit time for resuscitation and control of bleeding.
      To assess this technique, a prospective study was performed on twenty normal non
      bleeding parturients. The abdominal aorta was compressed by firm pressure with a
      closed fist just above the umbilicus. Leg and arm arterial blood pressures were
      measured and femoral artery pulsation felt before, during and after compression.
      Leg blood pressure was completely obliterated in 55% and significantly reduced (P
      < 0.01) in a further 10% of subjects. All of these subjects with reduced or
      absent leg blood pressure also had obliteration of the femoral pulse with
      compression. Systemic arterial blood pressure was not significantly elevated by
      successful aortic occlusion. Discomfort with the manoeuvre was significantly
      increased (P < 0.05) in the group of subjects that had successful aortic
      occlusion. It is recommended that external aortic compression be considered in
      severe life-threatening postpartum haemorrhage, particularly during stabilisation
      or transport of the patient. This simple manoeuvre may be used as an adjunct to
      other measures and could prove of benefit, especially in locations or situations
      where advanced medical assistance is geographically or temporally removed.

PMID- 7818063
TI  - A double-blind comparison of vecuronium administered by the Springfusor infusion
      device to vecuronium by intermittent bolus injection in critically ill adult
      patients.
AB  - To evaluate the Springfusor infusion device for clinical use in an Intensive Care
      Unit and to compare the technique of intermittent bolus and constant infusion of
      muscle relaxants, we undertook a prospective double-blind randomized placebo
      controlled study. Twenty critically ill ventilated patients requiring muscle
      paralysis were investigated. Although we could show no clinical advantage in
      infusing vecuronium, the Springfusor provided a more constant level of paralysis
      compared with hourly bolus doses. The device is robust, easy to use and reduces
      nursing workload. This may translate into cost-saving improvement in patient care
      if the Springfusor is used to provide muscle relaxation, sedation and analgesia.

PMID- 7818064
TI  - Alterations in endotracheal tube position during general anaesthesia.
AB  - The effect of head and neck movement and Trendelenburg tilt on endotracheal tube
      position, relative to the carina, was studied in fifty adult patients requiring
      intubation for elective surgery. On average, inward movement, that is shortening
      of the distance between the endotracheal tube tip and the carina, resulted from
      neck flexion (mean = -5.5 mm), whereas outward movement occurred with neck
      extension (mean = 6.3 mm). Neck rotation, to right and left, and Trendelenburg
      tilt did not show any trend towards inward nor outward movement (mean = 0.3
      mm/1.7 mm/-0.6 mm, respectively). Whilst these mean positional changes for
      flexion and extension confirm the findings of earlier investigations, our range
      of maximum inward and outward displacement for flexion (23 mm in/19 mm out),
      extension (21 mm in/33 mm out), rotation to right (19 mm in/17 mm out), to left
      (22 mm in/19 mm out) and Trendelenburg tilt (22 mm in/16 mm out) indicate that
      for any given postural change in any one patient, the direction and magnitude of
      endotracheal tube displacement is not readily predictable.

PMID- 7818065
TI  - Patient-controlled analgesia: a comparison with nurse-controlled intravenous
      opioid infusions.
AB  - Patient-controlled analgesia (PCA) with intravenous pethidine was compared with
      nurse-controlled pethidine infusions for pain relief in 200 patients after major
      abdominal or thoracic surgery. Pain, level of sedation, nausea and presence of
      other adverse effects, in addition to cumulative pethidine requirement, were
      measured for the first 24 hours after surgery. Both groups were similar for age,
      weight and type of surgery. There was no significant difference between the
      quality of analgesia achieved in both groups. The frequency and severity of
      adverse effects was also similar. The cumulative pethidine dose administered to
      both groups was identical. It is concluded that nurse-controlled opioid infusions
      are as effective as PCA and may be used as an alternative to PCA where this is
      either unavailable or unsuitable.

PMID- 7818067
TI  - Anaesthesia-induced rhabdomyolysis causing cardiac arrest: case report and review
      of anaesthesia and the dystrophinopathies.

PMID- 7818068
TI  - Adult respiratory distress syndrome caused by superior mesenteric artery
      syndrome.

PMID- 7818066
TI  - Anaesthesia for three-stage thoracoscopic oesophagectomy: an initial experience.
AB  - We report our experience in the anaesthetic management of five patients
      undergoing three-stage thoracoscopic oesophagectomy. One patient required
      conversion to open thoracotomy because of extensive pleural adhesions. The other
      four patients, aged between 68 and 78, were all chronic smokers with mid
      oesophageal squamous cell carcinoma. The duration of thoracoscopic surgery (and
      obligatory one-lung ventilation) ranged from 2.5 to 4 hours with total surgical
      time ranging from 7.5 to 9.5 hours. Anaesthetic considerations included the use
      of one-lung ventilation to provide surgical access, the cardiorespiratory effects
      of capnothorax, difficulties in assessing surgical blood loss during
      thoracoscopic dissection, crowding in the operating room with limitation of
      access to the patient and the risk of intraoperative dislodgement of the
      endobronchial tube. Postoperative pulmonary complications were not decreased in
      our patients despite the avoidance of thoracotomy. The thoracoscopic technique
      might contribute to pulmonary complications because of prolonged thoracoscopic
      dissection and unintentional pulmonary injuries. The concept of minimally
      invasive surgery needs further evaluation when the technique is applied in
      extensive procedures such as oesophagectomy.

PMID- 7818069
TI  - Pulmonary oedema due to upper airway obstruction caused by a Foley catheter.

PMID- 7818070
TI  - Painless epidural haematoma.

PMID- 7818071
TI  - Anaphylactic reaction to chlorhexidine in urinary catheter lubricant.

PMID- 7818072
TI  - Severe muscle weakness and hypokalaemia secondary to renal tubular acidosis.

PMID- 7818073
TI  - Continuous femoral nerve block to provide analgesia following femur fracture in a
      paediatric ICU population.

PMID- 7818074
TI  - Selectatec problems: again and again.

PMID- 7818075
TI  - Obstetric anaesthesia in Pacific Islands.

PMID- 7818076
TI  - A homemade device for monitoring neuromuscular blockade.

PMID- 7818077
TI  - Broken metal intubating stylet.

PMID- 7818078
TI  - Dilating peripheral veins--another suggestion.

PMID- 7818079
TI  - Airway anatomy and magnetic resonance imaging.

PMID- 7818080
TI  - Induction of anaesthesia in a patient with a bronchopleural fistula.

PMID- 7818081
TI  - Difficult intubation--comments on techniques.

PMID- 7818082
TI  - Tension pneumoperitoneum.

PMID- 7818083
TI  - Extreme resistance to general anaesthetics.

PMID- 7818084
TI  - "Difficult airway" or "problematic airway".

PMID- 7818085
TI  - Factors causing different properties at neuromuscular junctions in fast and slow
      rat skeletal muscles.
AB  - Neuromuscular junctions on fast and slow skeletal muscle fibers have different
      properties. Possible reasons for these differences were examined in adult rat
      soleus (SOL) muscle fibers reinnervated at new ectopic or old denervated sites by
      fast fibular (FIB) or slow SOL motoneurons. FIB motoneurons formed large ectopic
      junctions with a high density of nerve terminal varicosities (fast appearance),
      whereas SOL motoneurons formed small ectopic junctions with a low density of
      varicosities (slow appearance). Both FIB and SOL motoneurons formed small
      junctions with a slow appearance when reinnervating old SOL endplates. FIB nerves
      innervating ectopic sites and SOL nerves reinnervating old sites had the same
      appearance whether they contacted the SOL fibers alone (single innervation) or
      together (dual innervation). Continuous stimulation of the FIB nerve at 10 Hz for
      3-4 months reduced the size of ectopic FIB and intact extensor digitorum longus
      (EDL) junctions and caused a modest reduction in density of terminal varicosities
      in EDL. Junction size and muscle fiber diameter were positively correlated, but
      the slope describing this relation was steeper for FIB junctions than for SOL
      junctions. It is concluded that in the present system (1) motoneuron type and not
      muscle fiber type determines the fast or slow character of the neuromuscular
      junction. (2) denervated endplates of one type place stable and severe
      constraints on the termination pattern of reinnervating axons of another type,
      (3) the appearance of fast EDL junctions undergoes a modest fast to slow
      transformation when exposed to long-term slow pattern stimulation, and (4) not
      only the size of the muscle fibers, but also the type and firing pattern of the
      motoneurons and the spatial constraints at preformed endplates influence the
      relation between junction size and muscle fiber diameter.

PMID- 7818086
TI  - A comparative physiological and morphological study of periodontal ligament
      mechanoreceptors represented in the trigeminal ganglion and the mesencephalic
      nucleus of the cat.
AB  - A correlative morphological study was carried out on two electrophysiologically
      identified and located periodontal ligament mechanoreceptors in anaesthetised
      cats. One mechanoreceptor had its cell body in the mesencephalic nucleus and the
      other had its cell body in the trigeminal ganglion. Physiological recordings were
      made from each of their cell bodies. The two receptors were located by punctate
      and electrical stimuli in the labial aspect of the periodontal ligament of the
      left mandibular canine tooth. Both receptors had similar positions relative to
      the tooth apex and fulcrum and were situated in the labial part of the ligament
      in each tooth. The receptor loci were marked, and these regions were studied in a
      series of semi-thin and ultra-thin sections. Only Ruffini nerve endings were
      observed under each ink mark. Both Ruffini nerve endings branched, were
      unencapsulated and were incompletely surrounded by terminal Schwann cells with
      extensions projecting towards collagen bundles. The results indicate that
      periodontal ligament mechanoreceptors with cell bodies in the mesencephalic
      nucleus and those with their cell bodies in the trigeminal ganglion can both be
      Ruffini nerve endings. Furthermore, there was no apparent morphological
      difference between the two periodontal ligament mechanoreceptors.

PMID- 7818088
TI  - A quantitative ultrastructural investigation of tyrosine hydroxylase
      immunoreactive axons in the hairy skin of the guinea pig.
AB  - Besides its thermoregulatory role, the sympathetic innervation of the skin is
      involved in a modulation of sensory processing and trophic functions that has not
      been fully characterized. To investigate possible sites at which such
      sympathosensory interactions might occur, a quantitative ultrastructural study of
      the sympathetic innervation of the skin was attempted. The hairy skin of the
      guinea pig was studied because the sympathetic and sensory nerve axons in this
      species can easily be discriminated by the presence of immunoreactivity to the
      catecholamine-synthesizing enzyme, tyrosine hydroxylase (TH). The
      thermoregulatory role of the sympathetic skin innervation was highlighted by the
      almost exclusive sympathetic innervation of piloarrector muscles which contained
      62% (n = 195) of randomly selected TH-immunoreactive (TH-IR) axon profiles. Of TH
      IR pilomotor axons, 53% were filled with vesicles. Vesicle-containing axonal
      profiles were equally frequent around dermal arterial blood vessels (partly
      associated with mast cells), hair follicles, and within nerve fibre bundles
      surrounded by a perineural sheath, in each case accounting for about 3% of all
      dermal TH-IR axonal profiles. In contrast to piloarrector muscles, at these
      locations TH-IR (sympathetic) and non-reactive (sensory) axons were found in
      close association. These findings are in line with the previously reported
      inhibitory influence of sympathetic stimulation upon hair follicle afferents and
      perivascular sensory nerve terminals. In addition, they point to a yet
      underestimated target of sympathetic axon terminals, i.e. preterminal nerve fibre
      bundles.

PMID- 7818087
TI  - Interactions between growing thalamocortical afferent axons and the neocortical
      primordium in normal and reeler mutant mice.
AB  - The interactions between growing thalamocortical afferent axons and the
      neocortical primordium were examined during neocortical development of the mouse
      cerebrum, by labeling the afferents with the carbocyanine fluorescent dye, DiI,
      which was introduced into the dorsal thalamus of the fixed brains of control and
      reeler mutant mice. In the neocortical primordium of the control mouse, the
      labeled afferents running tangentially in the intermediate zone formed a dense
      plexus in the subplate, the layer below the cortical plate, as early as the 16th
      gestational day (E16). Small numbers of the afferents invaded the lower cortical
      plate at E16 and increasing numbers of labeled growing axons extended into the
      cortical plate at E17. At the 4th postnatal day (P4), labeled afferents grew
      radially up to the upper cortical plate and terminal arborizations of the
      afferents were evident in the forming layer IV. In contrast, in the E16 cerebrum
      of the reeler mutant mouse, in which the cortical layers are inverted, the
      labeled afferents traversed the neocortical primordium directly towards the
      superplate, the superficial layer above the cortical plate and the equivalent of
      the subplate in the control mouse. Thick bundles of labeled axons reached the
      superplate and made contact with the superplate neurons. At P4 in the reeler
      neocortex, the afferent axons that had reached the superplate began to change
      their direction of growth and turned towards the deeper layer. Electron
      microscopic observations at E16 revealed that immature synapses were formed on
      the somata of the subplate neurons in the control mouse, and similar immature
      synapses were also formed on the superplate neurons of the reeler mutant. At E16
      in the control, NGF receptor immunoreactivity was expressed in the intermediate
      zone, subplate and lower cortical plate, and the mode of expression corresponded
      to the distribution of thalamocortical afferents. At the same stage of the reeler
      mutant, expression of NGF receptor immunoreactivity was confined to the afferent
      axons that had grown through the neocortical primordium towards the superplate.
      In the control at E17, highly polysialylated NCAM (NCAM-H), a homophilic cell
      adhesion molecule, was expressed in the subplate, marginal zone and afferent
      axons. In the reeler mutant at the same stage, this adhesion molecule was
      expressed in both the superplate and the bundles of the afferent axons. These
      findings suggest that the subplate and the superplate, which are composed of
      neurons generated at the earliest stage, attract growing thalamocortical afferent
      axons specifically by a chemotropic mechanism through the expression of NGF
      receptor.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7818089
TI  - Histological identification of osteocytes in the allegedly acellular bone of the
      sea breams Acanthopagrus australis, Pagrus auratus and Rhabdosargus sarba
      (Sparidae, Perciformes, Teleostei).
AB  - The bone of advanced teleost fishes such as those of the family Sparidae is said
      to lack osteocytes or to be acellular. Acellularity has been determined by
      apparent lack of osteocyte lacunae. This study questions the validity of this
      criterion. Scanning electron and light microscopy of paraffin and resin sections
      were used to show that the sides of sea bream mandibles consist of laminar
      parallel-fibred bone that we call tubular bone, because it contains tubules, and
      localised regions of Sharpey fibre bone. Osteocytes lie along the walls of
      tubules that also contain collagen fibril bundles (T-fibres), or in the lumens of
      tubules that do not contain T-fibres. We show that the osteocytes are derived
      from osteoblasts. The T-fibre system is different from other fibre systems that
      have been described. The tubules enclose wide T-fibres (lenticular in cross
      section, maximum width about 8 microns) that taper at their ends and continue as
      thin T-fibres (round in cross-section, about 2 microns wide). The T-fibres
      originate in the periosteum. In mature tubular bone, spaces of increasing size
      develop around the osteocytes. Osteocytes are released from the bone matrix and
      become postosteocytes or bone-lining cells. Secondary bone lines the largest
      spaces. In Sharpey fibre bone, small osteocytes in small lacunae (about 2 microns
      wide) are found in columns parallel to the Sharpey fibres. Large osteocytes are
      found in large round spaces and are much larger than comparable osteocytes in
      lacunae in the bone of the salmon Salmo salar. We conclude that an absence of
      visible or conventional osteocyte lacunae does not mean that the cells themselves
      are absent. There are cells and two types of collagen fibre bundle in the
      tubules. The cells are osteocytes derived from osteoblasts, and these osteocytes
      apparently resorb bone with the result that large amounts of bone are destroyed.
      "Acellular" tubular and Sharpey fibre bone are types of cellular bone that differ
      from each other and from conventional cellular bone.

PMID- 7818091
TI  - Acrosomal status in fresh and frozen/thawed stallion spermatozoa evaluated by
      scanning electron microscopy.
AB  - Semen from stallions with equal fertility at natural services, but yielding semen
      with either satisfactory or poor fertilizing capability after freezing and
      thawing, was processed for scanning electron microscopy before and after freezing
      and thawing. In all fresh semen samples the following three categories of
      acrosomal defect were noticed: (1) minor fenestrations of the plasma membrane
      (PM) and outer acrosomal membrane (OAM), (2) complete vesiculation and loss of PM
      and OAM and (3) lack of a large circular part of PM and OAM. The frequency of
      these defects ranged from 15% to 27%. All frozen and thawed samples displayed
      defects of categories 1-3 at similar frequencies as the fresh ones. However,
      additional defects categorized as: (4) major fenestrations of PM and OAM and (5)
      complete vesiculation of PM and OAM without loss of the vesicles were noted upon
      freezing and thawing. The total frequency of defects categorized as 4 and 5
      ranged from 8% to 21%, and they seemed to be more frequent in stallions with poor
      fertility after freezing and thawing although the difference was not significant.
      Moreover, a particular defect categorized as (6) loosening of the whole acrosomal
      cap was found exclusively in stallions yielding semen with poor freezability.

PMID- 7818090
TI  - Quantitative investigations on the human entorhinal area: left-right asymmetry
      and age-related changes.
AB  - The total nerve cell numbers in the right and in the left human entorhinal areas
      have been calculated by volume estimations with the Cavalieri principle and by
      cell density determinations with the optical disector. Thick gallocyanin-stained
      serial frozen sections through the parahippocampal gyrus of 22 human subjects (10
      female, 12 male) ranging from 18 to 86 years were analysed. The laminar
      composition of gallocyanin (Nissl)-stained sections could easily be compared with
      Braak's (1972, 1980) pigmentoarchitectonic study, and Braak's nomenclature of the
      entorhinal laminas was adopted. Cell-sparse laminae dissecantes can more clearly
      be distinguished in Nissl than in aldehydefuchsin preparations. These cell-poor
      dissecantes, lamina dissecans externa (dis-ext), lamina dissecans 1 (dis-1) and
      lamina dissecans 2 (dis-2), were excluded from nerve cell number determinations.
      An exact delineation of the entorhinal area is indispensable for any kind of
      quantitative investigation. We have defined the entorhinal area by the presence
      of pre-alpha cell clusters and the deeper layers of lamina principalis externa
      (pre-beta and gamma) separated from lamina principalis interna (pri) by lamina
      dissecans 1 (dis-1). The human entorhinal area is quantitatively characterized by
      a left-sided (asymmetric) higher pre-alpha cell number and an age-related nerve
      cell loss in pre as well as pri layers. At variance with other CNS cortical and
      subcortical structures, the neuronal number of the entorhinal area appears to
      decrease continuously from the earliest stages analysed, although a secular trend
      has to be considered. The asymmetry in pre-alpha cell number is discussed in the
      context of higher human mental capabilities, especially language.

PMID- 7818093
TI  - Microscopic structure of the olfactory organ of the clearnose skate, Raja
      eglanteria.
AB  - The olfactory organ of juvenile clearnose skates (Raja eglanteria) was studied
      with the light and electron microscopes. The organ is ovoid in shape, and its
      free surface is complicated by the presence of some 20 lamellae. Each lamella has
      a folded surface lined by a typical neurosensory olfactory epithelium. Bipolar
      olfactory receptor neurons, ciliated sustentacular cells, and basal cells are the
      pre-eminent cellular components of the epithelium. Two types of receptor neurons,
      both bearing microvilli but not cilia, were identified. The type 1 neuron is
      similar to that previously described in other fishes. The type 2 neuron has a
      characteristic morphology justifying a separate description. Its dendritic knob
      is larger than that of type 1, and its microvilli, which are shorter and thicker,
      are straight and regularly arranged. Tight bundles of filaments provide a
      skeleton to each microvillus, and these filament bundles reach more than 5
      microns down into the dendrite. Type 2 receptor neurons have a well-developed
      Golgi complex and sparse rough endoplasmic reticulum (rER), whereas type 1
      receptor neurons have a less well-developed Golgi complex and a conspicuous
      system of rER lamellae. The mucous layer on the epithelial surface is provided by
      the secretion of goblet cells that are situated mostly in the peripheral regions
      of each lamella. Secretory granules in the sustentacular cells and glands in the
      lamina propria were not observed.

PMID- 7818092
TI  - The lymphatics of the liver.
AB  - An overview of our current knowledge of the hepatic lymph vessels is given, and
      the different lymph node stations that are related to the liver are described.
      The lymphatics of the liver itself can be divided into a superficial and a deep
      system. The superficial vessels are mainly situated in the liver capsule, the
      deep ones follow the triads of Glisson or the efferent hepatic veins. There are
      no direct communications between spaces in the liver parenchyma and the first
      lymphatic capillaries, which end blindly in the surrounding connective tissue.
      Nevertheless, the perisinusoidal space of Disse, the space of Mall, directly
      adjacent to the outer limiting plate of the parenchyma, and the space of
      Comparini, surrounding the sublobular hepatic veins can be regarded as
      prelymphatic spaces from which the hepatic lymph could originate. The
      extracellular matrix in the space of Disse is apparently continuous with the
      extraparenchymal areas of the connective tissue. Collagens and proteoglycans
      offer a morphological pathway for the transport of fluid, the physiological
      prerequisites of which are discussed.

PMID- 7818095
TI  - Distribution of C-CAM in developing oral tissues.
AB  - C-CAM is a cell surface glycoprotein that is involved in cell adhesion and may
      play a role in histogenesis and organogenesis. It is a member of the
      carcinoembryonic antigen (CEA) gene family, which is a subfamily of the
      immunoglobulin gene superfamily. We have analyzed the expression of C-CAM during
      normal and disturbed craniofacial development in the mouse by
      immunohistochemistry and in situ hybridization. Developmental disturbances were
      induced by retinoic acid (RA) treatment of pregnant mice. Normal and malformed
      fetuses were examined on days 14, 15, 16, 17 and 18 of gestation. The expression
      of C-CAM was detected first at day 16. With age, the signal became gradually
      stronger. C-CAM was detected in the epithelia of both ectodermal and mesodermal
      origin, including oral and respiratory epithelia, epithelia of the developing
      vessels, glands and their ducts. In the RA-treated fetuses, the expression of C
      CAM was higher in the epithelium of the oral cavity than in that of the nasal
      cavity, with a distinct borderline between differentiating nasal and oral
      epithelium of the palatal shelves. However, the submucosal nasal glands and ducts
      showed higher expression than oral glands in both normal and RA-treated mice. The
      expression of C-CAM did not differ significantly between control and RA-treated
      animals. The presence of C-CAM in all proliferating craniofacial epithelia
      indicates that this molecule may play an important role in development.

PMID- 7818096
TI  - Infrequent structures in cattle oocytes.
AB  - Uncommon and controversial structures in cattle oocytes were studied in dominant
      and subordinate follicles of unstimulated Bos taurus and zebu (Bos indicus), and
      in FSH-stimulated B. taurus cattle, before or after administration of
      cloprostenol. Growing oocytes were very rare in follicles more than or equal to 5
      mm in diameter. For the first time, special vesicles that may be involved in
      cortical granule synthesis were observed. Classical rough endoplasmic reticulum
      was very rare in unstimulated oocytes, but was seen at superovulation.
      Vacuolation of the nucleolus was a common feature in dominant oocytes that were
      collected after cloprostenol injection, except in superovulated cattle. Annulate
      lamellae were very rare or absent in oocytes of B. taurus, while they were more
      frequent in zebu oocytes.

PMID- 7818094
TI  - Gap junction proteins exhibit early and specific expression during
      intramembranous bone formation in the developing chick mandible.
AB  - The spatial and temporal expression of three closely related members of the
      connexin family of gap junction proteins (connexin42, Cx42; connexin43, Cx43; and
      connexin45, Cx45) was evaluated during bone formation in the mandibular process
      of the chick embryo. Mandibles of chick embryos from Hamburger and Hamilton stage
      25 (approximately 5 days) through 19 days of development were dissected, serially
      sectioned and processed for immunocytochemical localization, employing site
      specific anti-connexin antibodies. Our data revealed that (1) Cx43 was present
      throughout mandibular bone formation; (2) although it appeared to be associated
      with all bone cell types, Cx43 was concentrated in mesenchymal cells during the
      earliest stages in the osteogenic lineage; (3) most importantly, the localization
      of Cx43 at sites of bone formation appeared to precede the overt expression of
      the osteogenic phenotype; (4) by contrast, Cx45 was more restricted, spatially
      and temporally, in its distribution; (5) Cx42 expression was not detected in
      osteogenic tissue during mandibular bone formation. From all of the data
      obtained, Cx45 appeared to be associated with stages of bone formation
      characterized by the elaboration of matrix and the progressive expression of the
      differentiated osteogenic phenotype. Cx43 appeared to be associated with
      condensation of mesenchyme and the earliest stages of osteogenesis. Because of
      these associations, we propose that connexin expression may be necessary for the
      initiation of bone formation and the full expression of the osteogenic phenotype.

PMID- 7818098
TI  - Changes in the pattern of expression of alkaline phosphatase in the mouse uterus
      and placenta during gestation.
AB  - The development of the rodent chorio-allantoic placenta is a complicated process
      that results in the formation of a transport system capable of sustaining
      embryonic and fetal growth and development. Intimately linked to this process is
      alkaline phosphatase (AP), a cell-surface glycoprotein that possibly functions as
      a transport protein. In the present study, we have mapped the location of AP
      expressing cells in the mouse utero-placental unit during the development of the
      chorio-allantoic placenta by use of enzyme histochemistry and in situ
      hybridization histochemistry. We found that at implantation the expression of the
      tissue non-specific AP (TNAP) gene is located exclusively in the decidua and that
      most of this decidual expression ceases as the placenta starts to form. One
      exception is a mesometrially located marginal zone of the decidua, which
      continues to express the TNAP gene until day 12 and the active protein until at
      least day 16. Trophoblasts of the chorion already express AP before the time of
      fusion with the ectoplacental cone, after which AP is expressed by trophoblasts
      of the resulting ectoplacental plate. AP expression in the mature chorio
      allantoic placenta is localized in the placental labyrinth and spongy zones. In
      the latter zone, expression ceases on about day 14. Giant trophoblasts start to
      express AP on about day 10, with some cells still positive for AP at day 16. The
      yolk sac does not express AP at any developmental stage. The results show that AP
      expression during placental development is neither restricted to cells known to
      be involved in transport, nor expressed in all cells thought to be involved in
      this transport. This may indicate that AP is not merely a transport protein but
      has additional functions.

PMID- 7818097
TI  - Sequences of intrafusal fiber formation are muscle-dependent in rat hindlimbs.
AB  - A rat muscle spindle typically contains four intrafusal fibers-one nuclear bag2,
      one nuclear bag1 and two nuclear chain fibers. We compared the sequence of
      formation of the three intrafusal fiber types among the tibialis anterior (TA),
      soleus (SOL) and medial gastrocnemius (MG) muscles using immunocytochemistry of
      spindle-specific myosin heavy chain isoforms. Spindles of the TA began to
      differentiate earlier and acquired the full complement of intrafusal fibers
      sooner than spindles of the SOL or MG muscles. At the onset of spindle assembly,
      the intrafusal myotubes expressed myosin heavy chains similar to those expressed
      by extrafusal myotubes. The first intrafusal myotube then differentiated into the
      bag2 fiber regardless of the muscle. However, the fate of the second-forming
      intrafusal myotube varied among the muscles studied. It usually differentiated
      into a chain fiber in the TA, into a bag1 fiber in the SOL, and into either a
      bag1 or a chain in the MG. The fate of the third-forming intrafusal myotube was
      reciprocal to that of the second; i.e. in those spindles in which the bag1 fiber
      was second to form, a chain was third, and vice versa. The fourth and last
      intrafusal myotube gave rise to a chain fiber. The inter- and intramuscular
      variability in the fate of intrafusal myotubes of the second and third generation
      argues against the existence of a program intrinsic to the myotubes that would
      mandate their differentiation along specific paths. Rather, an extrinsic
      regulatory factor, probably associated with the primary afferent neuron, may
      govern differentiation of pluripotential myotubes into particular types of
      intrafusal fiber. The fate of the intrafusal myotubes might then depend on the
      timing of the regulatory effect of afferents relative to the stage of development
      of the intrafusal bundle.

PMID- 7818099
TI  - Action of testosterone on the anti-mullerian activity of the chick embryonic
      testis assayed in vivo by organotypic grafting.
AB  - The implantation of embryonic testis grafts into female chick embryos induces the
      regression of their mullerian ducts (MDs) in a certain number of cases. The
      treatment of either the grafts or the grafted females with testosterone
      propionate (TP) results in a significant increase in the number of MD regressions
      observed. Our data are interpretable in terms of a direct activation by TP of the
      anti-mullerian activity of the embryonic testis. We discuss a possible mechanism
      accounting for the synergistic action of testosterone and anti-mullerian hormone.

PMID- 7818100
TI  - Postnatal development of parvalbumin immunoreactivity in striated muscles of the
      rat.
AB  - The presence of parvalbumin, a calcium-binding protein, has been correlated with
      the maturation of locomotor activity in developing striated muscle. In the
      present study, postnatal parvalbumin immunoreactivity is examined in the tibialis
      anterior, intercostal, diaphragm and intrinsic muscles of the tongue of the rat
      to gather a better understanding of the different developmental patterns.
      Parvalbumin immunoreactivity appears in the anterior tibialis muscle by day 4,
      and reaches an adult checkerboard pattern 2 days later. In contrast, parvalbumin
      immunoreactivity in the intrinsic muscles of the tongue, and in diaphragm and
      intercostal muscles, which are active near birth, does not appear until the 2nd
      week. Therefore, these features suggest that parvalbumin immunoreaction is not
      exclusively dependent on functional activity. In addition, the finding that
      differences in parvalbumin expression do not correlate in time with the
      differentiation of fiber types as judged by myosin ATPase activity, suggests that
      myosin and parvalbumin might be regulated by different mechanisms.

PMID- 7818101
TI  - Coagulation and packed red blood cell transfusions.

PMID- 7818102
TI  - Thinner than blood.

PMID- 7818103
TI  - Oxygen consumption and cardiovascular function in children during profound
      intraoperative normovolemic hemodilution.
AB  - The clinically acceptable limit of acute normovolemic, normothermic hemodilution,
      a standard procedure in scoliosis surgery, is not yet well defined. Eight ASA
      class I patients undergoing idiopathic scoliosis correction were administered a
      standard anesthetic with 100% oxygen and controlled ventilation. Hemodilution was
      accomplished by exchanging whole blood for 5% albumin in 0.9% saline. Blood
      gases, acid-base status, and circulatory variables were recorded prior to and
      after hemodilution, and every 30 min throughout surgery. The impact of
      hemodilution was judged by mixed venous oxygen saturation which was maintained at
      > or = 60%, while intravascular volume was maintained with the 5% albumin
      solution. Reinfusion of the autologous blood was completed by the end of surgery.
      In the eight controlled cases in which normovolemic hemodilution was studied,
      hemoglobin levels decreased from 10.0 +/- 1.6 g/dL to 3.0 +/- 0.8 g/dL. Mixed
      venous oxygen saturation decreased from 90.8% +/- 5.4% to 72.3% +/- 7.8%. Oxygen
      extraction ratio increased from 17.3% +/- 6.2% to 44.4% +/- 5.9%. Oxygen delivery
      decreased from 532.1 +/- 138.1 mL.min-1.m-2 to 260.2 +/- 57.1 mL.min-1.m-2, while
      global oxygen consumption did not decrease and plasma lactate did not appreciably
      increase. Central venous pressure increased and peripheral resistance decreased
      during hemodilution. Cardiac index increased, heart rate remained essentially
      constant, and left ventricular stroke work index did not decrease significantly.
      No patients suffered clinically adverse outcomes. Global oxygen transport and
      myocardial work can be maintained at extreme normovolemic anemia. Our evidence
      suggests that stages of normovolemic hemodilution more severe than previously
      reported may be clinically acceptable for young, healthy patients during
      normocarbic anesthesia.

PMID- 7818105
TI  - Vomiting after outpatient tonsillectomy and adenoidectomy in children: the role
      of nitrous oxide.
AB  - The role of nitrous oxide anesthesia in causing postoperative vomiting (POV) was
      studied in 60 children undergoing outpatient tonsillectomy and adenoidectomy. In
      this controlled, randomized, double-blind investigation, anesthesia was induced
      by inhalation of a volatile anesthetic in both groups. The nonnitrous oxide group
      received no nitrous oxide, even during induction of anesthesia. Designated nurses
      in the postanesthesia care unit (PACU) who were blinded to the anesthetic
      technique evaluated the incidence and the severity of the patient's emetic
      symptoms, both in the PACU as well as after discharge. Pharmacologic intervention
      was administered on the basis of evaluation by the nurses. Although a high
      incidence of POV was noted in both groups, there was no difference in either the
      incidence or the severity of POV between the group receiving nitrous oxide and
      the group receiving no nitrous oxide.

PMID- 7818104
TI  - A double-blind evaluation of ketorolac tromethamine versus acetaminophen in
      pediatric tonsillectomy: analgesia and bleeding.
AB  - The study was designed to compare intravenous ketorolac to rectal acetaminophen
      for analgesia and bleeding in pediatric patients undergoing tonsillectomy. We
      studied 50 patients, aged 2-15 yr undergoing tonsillectomy with or without
      adenoidectomy. In a randomized, prospective double-blind fashion, patients were
      assigned to receive either ketorolac (1 mg/kg) or rectal acetaminophen (35
      mg/kg). Bleeding was evaluated by measuring intraoperative blood loss and noting
      extra measures required to obtain hemostasis. Bleeding times were also measured
      before and during surgery. Pain was evaluated using a standard objective pain
      score for the first 3 h. Persistent pain was treated with morphine,
      acetaminophen, and codeine and recorded for 24 h. Blood for determination of
      acetaminophen levels was drawn at 20 and 40 min after the administration of study
      drugs. Pain scores were not significantly different between the ketorolac and
      acetaminophen groups. The majority of patients in both groups required additional
      opioid in the postoperative period. Acetaminophen levels were all less than the
      therapeutic range. Intraoperative bleeding times were normal in all patients, but
      blood loss was significantly higher in the ketorolac group (2.67 mL/kg) compared
      to the acetaminophen group (1.44 mL/kg), P = 0.025. Significantly more measures
      to achieve hemostasis were required in the ketorolac group (P = 0.012). We
      conclude that ketorolac is no more effective than high-dose rectal acetaminophen
      for analgesia in the patient undergoing tonsillectomy. Hemostasis during
      tonsillectomy was significantly more difficult to achieve in patients receiving
      ketorolac.

PMID- 7818106
TI  - The risk of infection from epidural analgesia in children: a review of 1620
      cases.
AB  - We reviewed cases to determine whether suspected or confirmed epidural infection
      was associated with epidural analgesia for 1620 infants, children, and
      adolescents treated over a 6-yr period at Children's Hospital, Boston.
      Postoperative patients (1458/1620) received epidural infusions for a median of 2
      days (range, 0-8 days). No postoperative patient had an epidural abscess. One 10
      yr-old with terminal malignancy received thoracic epidural analgesia via two
      successive catheters over a 4-wk period. She had Candida colonization of the
      epidural space along with necrotic epidural tumor. A second oncology patient and
      two patients with reflex sympathetic dystrophy were evaluated for epidural
      abscess, but none was found. We conclude that the risk of epidural infection is
      quite low in pediatric postoperative patients receiving short-term
      catheterization. Use of prolonged epidural analgesia in the management of chronic
      pain in children requires careful monitoring of warning signs of infection.

PMID- 7818107
TI  - Nitrous oxide depresses the H-reflex in children with cerebral palsy.
AB  - Hoffmann's reflex or H-reflex (HR) is an electrically elicited reflex that
      measures excitability of motoneurons and shares some physiologic properties with
      the deep tendon reflex. Children with tendon hyperreflexia due to cerebral palsy
      usually have higher amplitude HRs. Nitrous oxide (N2O) depresses the HR in
      patients with normal spinal reflexes, although the effect of N2O in conditions
      with hyperreflexia such as cerebral palsy is not known. We propose to determine
      the effect of N2O on the amplitude of the HR under general anesthesia in children
      with hyperreflexia due to cerebral palsy. We studied eight children undergoing
      selective dorsal rhizotomy (SDR) for the relief of spasticity. The maximum
      amplitudes of the HR (HRmax) and direct motor response (MRmax) were routinely
      evoked under the following anesthetic conditions: 1) sufentanil and 66% N2O/33%
      oxygen; and 2) sufentanil and 100% oxygen. The HRmax amplitude was significantly
      lower when N2O was part of the inspired gas mixture. The differences between the
      no N2O and the 66% N2O groups were significant. The MRmax did not change
      significantly. Abnormal spinal reflexes seen in spastic diplegia can be abolished
      by inhaled N2O. This finding also suggests that N2O-induced depression of spinal
      reflexes should be a consideration during physiologic monitoring of the spinal
      cord under general anesthesia.

PMID- 7818108
TI  - Changes in mortality after total hip and knee arthroplasty over a ten-year
      period.
AB  - A retrospective review of in-hospital mortality after total hip and total knee
      arthroplasty was performed to determine whether extensive changes in anesthesia
      care, introduced in this institution in July 1986, were associated with changes
      in mortality rates. From 1981 to 1985, the mortality rate was 0.39% (23 of 5874
      patients) and from 1987 to 1991, the mortality rate was 0.10% (10 of 9685
      patients) (P = 0.0003). Significant reductions in mortality rate were observed
      for both total hip arthroplasty (from 0.36% to 0.10%) (P = 0.0277) and total knee
      arthroplasty (from 0.44% to 0.10%) (P = 0.0131). The mortality rate of 0.10% is
      significantly less than previously published rates. Marked changes in anesthesia
      management were associated with a significant reduction in mortality after total
      hip and knee arthroplasty.

PMID- 7818109
TI  - Does nitrous oxide affect coronary microcirculation? An intravital microscopic
      study in the canine heart.
AB  - The safe use of nitrous oxide, in particular in patients with coronary artery
      disease, has been questioned. This study was designed to determine whether
      nitrous oxide directly affects global coronary hemodynamic variables and coronary
      arteriolar microvessels in the absence of changes of myocardial oxygen
      consumption. In dogs the effects of nitrous oxide were evaluated during
      normotension (NT, intravenous [IV] piritramid, nitrogen/oxygen; and NT/N2O, IV
      piritramid, nitrous oxide/oxygen) and during hypotension (MAP 60 mm Hg) (HT, IV
      piritramid, halothane, nitrogen/oxygen; and HT/N2O, IV piritramid, halothane,
      nitrous oxide/oxygen). The diameter of coronary arteriolar microvessels (range,
      20-450 microns) was assessed by intravital fluorescence microscopy. Myocardial
      blood flow was determined by radioactive microspheres. Systemic and coronary
      hemodynamics, as well as arteriolar microvessel diameters, were comparable
      between NT and NT/N2O. During HT, nitrous oxide (HT/N2O) affected neither
      systemic nor coronary hemodynamics. Moreover, there was no obvious difference in
      the diameters of coronary microvessels between HT and HT/N2O. In conclusion,
      nitrous oxide, whether at normotensive or hypotensive conditions, neither
      influences coronary arteriolar tone nor reduces or redistributes myocardial blood
      flow.

PMID- 7818110
TI  - Direct effects of halothane on coronary blood flow, myocardial oxygen
      consumption, and myocardial segmental shortening in in situ canine hearts.
AB  - Previous in vivo studies of the coronary vascular effects of halothane (HAL) were
      complicated by varying hemodynamic conditions and global cardiac work demands.
      Accordingly, the current study evaluated changes in coronary blood flow (CBF) and
      associated variables during selective intracoronary administrations of HAL in in
      situ canine hearts using an extracorporeal-controlled pressure perfusion system.
      Findings during HAL were compared to those during isoflurane (ISO). The left
      anterior descending coronary artery (LAD) of 8 open-chest dogs anesthetized with
      fentanyl and midazolam was perfused at constant pressure (109 +/- 2 mm Hg) with
      HAL-free arterial blood or with blood equilibrated in an extracorporeal
      oxygenator with HAL (0.5%, 1.0%, 2.0% in 95% O2-5.0% CO2). In the LAD bed,
      measurements of CBF were obtained with an electromagnetic flowmeter and used to
      calculate myocardial oxygen consumption (MVO2). Percent segmental shortening
      (%SS) was measured with ultrasonic crystals. Changes in CBF by HAL were compared
      to those during maximal vasodilation with adenosine. Separate studies (n = 5)
      were performed using 1.4% [1 minimum alveolar anesthetic concentration (MAC)] ISO
      and the findings compared to those during an equianesthetic (1.0%) concentration
      of HAL. HAL caused concentration-dependent increases in CBF, and decreases in
      MVO2 and %SS. With 2.0% HAL, the level of CBF was 50% of the maximal adenosine
      induced response. At equianesthetic concentrations, HAL caused increases in CBF
      that were one-third of those caused by ISO, while the decreases in MVO2 and %SS
      caused by the drugs were not significantly different.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7818111
TI  - Dose-response effects of intravenous clonidine on stress response during
      induction of anesthesia in coronary artery bypass graft patients.
AB  - This study was designed to evaluate the dose-response effects of different doses
      of clonidine on the stress response to laryngoscopy and endotracheal intubation.
      In a randomized, double-blind study, 48 coronary artery bypass grafting (CABG)
      patients received 0, 2, 4, or 6 micrograms/kg clonidine as an intravenous (IV)
      infusion during a 15-min period 30 min prior to induction of anesthesia with
      etomidate (0.3 mg/kg), fentanyl (5-7 micrograms/kg), and pancuronium (0.1 mg/kg).
      Sedation was assessed prior to induction of anesthesia. Cardiovascular variables
      and catecholamine plasma levels were measured at predefined intervals. Additional
      bolus doses of etomidate and fentanyl for suppression of stress-induced reactions
      were administered if predefined limits of heart rate and blood pressure were
      exceeded. Clonidine 4 and 6 micrograms/kg significantly attenuated hemodynamic
      and adrenergic reactions to stress, reduced pharmacologic interventions, and
      increased sedation. However, clonidine 6 micrograms/kg was not more effective
      than 4 micrograms/kg, and clonidine 2 micrograms/kg was equally effective as
      placebo. We conclude that clonidine 4 micrograms/kg IV is the appropriate dose to
      attenuate the stress response to laryngoscopy in CABG patients. Side effects
      limiting the use of IV clonidine were not observed.

PMID- 7818112
TI  - Detection of tissue hypoxia by arteriovenous gradient for PCO2 and pH in
      anesthetized dogs during progressive hemorrhage.
AB  - The present study tested the hypothesis that, during acute bleeding, the
      development of tissue hypoxia might be reflected by an abrupt widening in
      arteriovenous gradient for PCO2 (AV PCO2) and for pH (AV pH) as accurately as by
      an increase in blood lactate levels. Twenty-four anesthetized (isoflurane 1.4%
      end-tidal), paralyzed, and mechanically ventilated dogs submitted to progressive
      hemorrhage were studied. Oxygen uptake (VO2) was derived from expired gas
      analysis and oxygen delivery (DO2) was calculated by the product of the
      thermodilution cardiac index and the arterial O2 content. During the first part
      of the protocol, VO2 remained stable as the progressive reduction in DO2 was
      associated with a corresponding increase in O2 extraction (O2ER). Blood lactate
      increased slightly but not significantly. AV PCO2 and AV pH increased
      significantly, essentially related to venous respiratory acidosis. The critical
      value of DO2 below which VO2 decreased was 8.95 +/- 1.60 mL.min-1.kg-1. Below
      this value, there was a marked increase in blood lactate and an abrupt widening
      in AV PCO2 and AV pH gradients. The critical value of DO2 obtained from blood
      lactate, AV PCO2 and AV pH were similar to those obtained from VO2 (8.60 +/-
      1.12; 8.73 +/- 1.40; 8.78 +/- 1.37, respectively; P = not significant). A
      significant correlation was found, during the hemorrhage protocol, between blood
      lactate and AV PCO2 (r = 0.84; P < 0.001) or AV pH (r = 0.78; P < 0.001).
      Therefore, AV PCO2 and AV pH represent simple but reliable indicators of tissue
      hypoxia during hemorrhagic shock.

PMID- 7818113
TI  - Factors associated with postoperative pulmonary complications in patients with
      severe chronic obstructive pulmonary disease.
AB  - The purpose of this study was to determine the incidence of different
      postoperative pulmonary complications (PPCs) and their associated risk factors in
      patients with severe chronic obstructive pulmonary disease (COPD) (forced
      expiratory volume in 1 s [FEV1] < or = 1.2 L and FEV1/forced vital capacity (FVC)
      < 75%) undergoing noncardiothoracic operations. Thirty-nine of 105 patients (37%)
      had one or more PPCs (death, pneumonia, prolonged intubation, refractory
      bronchospasm, or prolonged intensive care unit (ICU) stay). Thirty-eight of 39
      patients (97%) with a PPC had an anesthetic duration > 2 h. Our study patients
      had a 47% 2-yr mortality rate. We determined specific risk factors for each PPC
      by analyzing potential preoperative and intraoperative risk factors. Pulmonary
      factors alone do not predict the likelihood of PPCs in severe COPD patients.
      Multiple logistic regression identified composite scoring systems, such as the
      ASA physical status, as the best preoperative predictors of PPCs, probably
      because they include both pulmonary and nonpulmonary factors. During the
      intraoperative period, avoiding general anesthesia with tracheal intubation may
      decrease the risk of postoperative bronchospasm. Shortening the duration of
      surgery and anesthesia may decrease the risk of prolonged ICU stay.

PMID- 7818114
TI  - Ropivacaine 0.25% versus bupivacaine 0.25% for continuous epidural analgesia in
      labor: a double-blind comparison.
AB  - We compared the effects of continuous epidural infusion of ropivacaine 0.25% with
      bupivacaine 0.25% on pain relief and motor block during labor, and on the
      neonate. Seventy-six full-term parturients in active labor requiring epidural
      analgesia were randomly allocated to receive either bupivacaine 0.25% or
      ropivacaine 0.25%. Fifteen minutes after a loading dose of 10 mL of the study
      drug, an epidural infusion with the same drug was started at 6-12 mL/h to
      maintain an adequate block. Top-up doses of 6-10 mL were given as required. At
      full cervical dilation, the epidural infusion was discontinued. The onset of pain
      relief (verbal scale), contraction pain (visual analog scale), intensity of motor
      block (modified Bromage scale), and duration of motor block were not
      statistically different between the groups. Apgar scores at 1 and 5 min after
      delivery were comparable. There was a higher proportion of the neonates in the
      ropivacaine group (26/31 = 84%) who had a neurologic and adaptive capacity score
      (NACS) > or = 35 2 h after delivery than in the bupivacaine group (18/29 = 62%).
      We conclude that ropivacaine 0.25% and bupivacaine 0.25% are equally effective
      for epidural pain relief during labor. Ropivacaine may have an advantage over
      bupivacaine regarding neonatal neurobehavioral performance during the first few
      hours after delivery, although further studies will be required to substantiate
      this.

PMID- 7818115
TI  - Neurolytic celiac plexus block for treatment of cancer pain: a meta-analysis.
AB  - We performed a meta-analysis of the efficacy and safety of neurolytic celiac
      plexus block (NCPB) for cancer pain. A literature search yielded 59 papers, but
      data on NCPB in two or more patients was available in only 24 papers. Twenty-one
      studies were retrospective, one was prospective, and two were randomized and
      controlled. Cancer type was stated in 1117 of 1145 patients reported (63%
      pancreatic, 37% nonpancreatic). A bilateral posterior approach with 15-50 mL
      [corrected] of 50%-100% alcohol was the most common technique. Nonradiologically
      guided NCPB was performed in 246 patients (32%); guidance was by computed
      tomography (CT) in 214 (28%), radiograph in 271 (34%), fluoroscopy in 36 (5%), or
      ultrasound in 7 (< 1%). Good to excellent pain relief was reported in 878/989
      patients (89%) during the first 2 wk after NCPB. Long-term followup beyond 3 mo
      revealed persistent benefit. Partial to complete pain relief continued in
      approximately 90% of patients alive at 3 mo post-NCPB and in 70%-90% until death
      even if beyond 3 mo post-NCPB. Patients with pancreatic cancer responded
      similarly to those with other intraabdominal malignancies. Common adverse effects
      were transient, including local pain (96%), diarrhea (44%), and hypotension
      (38%); complications occurred in 2%. This analysis suggests that: 1) NCPB has
      long-lasting benefit for 70%-90% of patients with pancreatic and other
      intraabdominal cancers, regardless of the technique used; 2) adverse effects are
      common but transient and mild; and 3) severe adverse effects are uncommon.

PMID- 7818116
TI  - Pharmacokinetics and pharmacodynamics of oxycodone when given intravenously and
      rectally to adult patients with cancer pain.
AB  - The single-dose pharmacokinetics and pharmacodynamics of oxycodone administered
      by the intravenous and rectal routes were determined in 12 adult cancer patients
      with moderate to severe cancer pain (visual analog scale [VAS] score,
      approximately 5). Oxycodone was administered by the intravenous and rectal routes
      with open drug administration and a cross-over design. After single-dose
      intravenous administration (7.9 +/- 1.5 mg, mean +/- SD), the mean (+/- SD)
      terminal half-life was 3.4 h (+/- 1.1), the mean (+/- SD) plasma clearance was
      45.4 L/h (+/- 10.1), and the mean (+/- SD) volume of distribution in the terminal
      phase was 3.0 L/kg (+/- 1.1). After rectal oxycodone (30 mg), the mean (+/- SD)
      absorption lag time was 0.52 h (+/- 0.29) and the mean (+/- SD) absolute
      bioavailability was 61.6% (+/- 30.2%). Intravenous oxycodone was associated with
      a rapid onset of pain relief (5-8 min) in contrast to the 0.5- to 1.0-h delay
      observed after rectal administration. However, rectal oxycodone provided
      analgesia of much longer duration (approximately 8-12 h) than did intravenous
      oxycodone (approximately 4 h). There were no significant differences (P > 0.05)
      in the incidence and severity of side effects between intravenous and rectal
      oxycodone. The marked interindividual variation observed in the pharmacokinetics
      and pharmacodynamics of oxycodone in this study emphasizes the need for
      individualized dosing regimens.

PMID- 7818117
TI  - Preoperative antiplatelet therapy does not increase the risk of spinal hematoma
      associated with regional anesthesia.
AB  - One thousand orthopedic procedures in 924 patients given spinal or epidural
      anesthesia were prospectively studied to determine the risk of hemorrhagic
      complications associated with regional anesthesia. A history of excessive
      bruising or bleeding was elicited in 115 (12%) patients. Preoperative
      antiplatelet medications were taken by 386 (39%) patients. Aspirin was the most
      frequently reported antiplatelet drug and was taken by 193 patients. Subcutaneous
      heparin was administered to 22 patients before surgery on the operative day. One
      patient of 774 tested had a preoperative platelet count less than 100,000/mm3. In
      addition, 26 of 171 preoperative prothrombin times and 10 of 115 preoperative
      activated partial thromboplastin times were longer than normal. Only 31
      preoperative bleeding times were performed; five were prolonged. There were no
      documented spinal hematomas (major hemorrhagic complications). Blood was noted
      during needle or catheter placement (minor hemorrhagic complication) in 223 (22%)
      patients, including 73 patients with frank blood in the needle or catheter.
      Preoperative antiplatelet therapy did not increase the incidence of minor
      hemorrhagic complications. However, female gender, increased age, a history of
      excessive bruising/bleeding, surgery to the hip, continuous catheter anesthetic
      technique, large needle gauge, multiple needle passes, and moderate or difficult
      needle placement were all significant risk factors. The lack of correlation
      between antiplatelet medications and bloody needle or catheter placement
      (producing clinically insignificant collections of blood in the spinal canal or
      epidural space) is strong evidence that preoperative antiplatelet therapy is not
      a significant risk factor for the development of neurologic dysfunction from
      spinal hematoma in patients who undergo spinal or epidural anesthesia while
      receiving these medications.

PMID- 7818118
TI  - Efficacy of an epidural test dose in adult patients anesthetized with isoflurane:
      lidocaine containing 15 micrograms epinephrine reliably increases arterial blood
      pressure, but not heart rate.
AB  - When continuous epidural anesthesia is combined with general anesthesia, the only
      objective sign of intravascular migration of the epidural catheter are the
      increments of heart rate (HR) or arterial blood pressure after a local anesthetic
      test dose containing epinephrine. However, the efficacy of a simulated
      intravenous (IV) test dose in adult patients under general anesthesia has not
      been determined. Thirty adult patients were randomly assigned to one of two
      groups, each of which was anesthetized with 1% end-tidal isoflurane and nitrous
      oxide after endotracheal intubation. The epinephrine group (n = 15) was given 3
      mL of 1.5% lidocaine with epinephrine (1:200,000) IV to simulate an IV
      administered epidural test dose. The saline group (n = 15) was identical to
      epinephrine group, but received 3 mL of normal saline IV. HR and arterial blood
      pressure were measured at 20-s intervals for 4 min after IV injection. In the
      epinephrine group, significant increases in HR compared with the baseline value
      were observed from 40 to 80 s after the IV test dose with a mean maximum HR
      increase of 24 +/- 2 bpm (mean +/- SEM) occurring at 48 +/- 3 s. However, 5 of 15
      patients in the epinephrine group developed HR increments smaller than 20 bpm
      (sensitivity 67%). Since HRs were essentially unchanged in the saline group,
      specificity, positive predictive value (+PV), and negative predictive value (-PV)
      were 100%, 100%, and 75%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7818119
TI  - Sympathovagal effects of spinal anesthesia assessed by heart rate variability
      analysis.
AB  - Heart rate variations (HRV) result from moment-to-moment changes in sympathetic
      and parasympathetic activity in response to many conditions. These two neural
      inputs to the heart can be identified by analyzing power spectra of HRV for
      frequency components at the vasomotor (low-frequency [LF]) and the respiratory
      (high-frequency [HF]) rhythms. HRV analysis has been used successfully in humans
      to noninvasively evaluate the autonomic responses to specific maneuvers and
      drugs, as well as responses to more chronic preexisting pathologic conditions.
      The effects of an isolated "acute" withdrawal of sympathetic activity in humans,
      however, have not as yet been evaluated using an autoregressive (AR) technique.
      We examined HRV using this technique in a group of patients receiving
      subarachnoid block for abdominal surgery. The sensory levels achieved were within
      the range of those reported to interrupt sympathetic outflow to the heart.
      Electrocardiograms were recorded and subjected to AR analysis. AR analysis of HRV
      after spinal anesthesia revealed significant decreases in both dominant frequency
      components (LF and HF) that occur between 0.03 Hz and 0.5 Hz. These reductions
      coincided with blockade of cardiac sympathetic outflow after cephalad spread of
      the spinal block. The power spectra were almost abolished in patients with
      sensory blocks reaching T1-2. The decreases in amplitude of the LF and HF
      components, therefore, act as markers of diminished sympathetic and
      parasympathetic activity to the heart, while the ratio of LF:HF indicated that
      sympathovagal balance was predominantly maintained during most of the
      block.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7818120
TI  - Hemodynamic and analgesic effects of clonidine added repetitively to continuous
      epidural and spinal blocks.
AB  - Clonidine in spinal and epidural blocks prolongs anesthesia, but can cause
      hypotension and bradycardia. The aim of our study was to compare hemodynamic and
      analgesic effects of spinal versus epidural clonidine alone and after repetitive
      dosing. In a prospective, randomized, double-blind study, we evaluated 40
      patients scheduled for lower extremity orthopedic surgery under continuous spinal
      or epidural anesthesia with bupivacaine 0.5% (initial dose 5 mg and 50 mg,
      respectively). In either spinal or epidural technique one-half of patients
      received clonidine (150 micrograms) in addition to bupivacaine. Repeat doses of
      the same anesthetic mixture were allowed in cases of subsequent pain. Mean
      arterial pressure (MAP) and heart rate were recorded for 6 h after each
      injection. Duration of clinically useful anesthesia was defined as the time from
      drug administration to first sensation of pain. Intrathecal, but not epidural,
      clonidine decreased MAP significantly compared with bupivacaine alone. MAP after
      intrathecal clonidine with bupivacaine was lower than epidural clonidine with
      bupivacaine 5 and 6 h after injection. Repetitive administration caused no
      further decrease in MAP. Onset time required to surgical anesthesia (sensory
      block of T11) did not differ among the four groups. Duration of spinal and
      epidural anesthesia was increased more than two fold by clonidine. In summary,
      the addition of clonidine prolongs analgesia by either route. These results may
      be explained by clonidine's sites of action in hemodynamic control and the
      density of bupivacaine-induced block.

PMID- 7818121
TI  - Bupivacaine enantiomer pharmacokinetics after intercostal neural blockade in
      liver transplantation patients.
AB  - Bupivacaine, being a racemic local anesthetic, exists as an equal mixture of its
      component enantiomers R(+)- and S(-)-bupivacaine, which behave
      pharmacokinetically as independent drugs after injection into the body.
      Intercostal neural blockade using bupivacaine was performed for postoperative
      analgesia in 12 patients after orthotopic liver transplantation. Arterial blood,
      sampled serially, was assayed by enantioselective high-performance liquid
      chromatography for R(+)- and S(-)-bupivacaine. The average of the simultaneous
      R(+):S(-) ratios of blood bupivacaine concentrations in the 12 patients was 0.74
      (SD 0.11); however, the use of a population mean value or a mean value for any
      patient denies the time-dependence of this entity. The blood enantiomer
      concentration difference was reflected in the maximum measured concentrations
      which, after the first dose, were, respectively, 0.38 (SD 0.19) and 0.52 (SD
      0.28) mg.L-1.100 mg-1 RS-bupivacaine administered (P = 0.0003). The difference in
      blood concentrations between the enantiomers, reflected by the R(+):S(-) ratio
      being less than unity, could be explained by a greater mean total body clearance
      and a larger apparent volume distribution of R(+)-bupivacaine. Elimination of
      both enantiomers was prolonged in these patients after liver transplantation
      compared to data from the literature, but there was no tendency for either
      enantiomer to accumulate selectively, even upon repeated dosing. We conclude that
      this demonstration of differences in pharmacokinetics (and, in laboratory
      studies, also in pharmacodynamics) between the bupivacaine enantiomers points to
      the need for future studies to recognize the enantiomeric duality of this local
      anesthetic.

PMID- 7818122
TI  - Packed red cells in acute blood loss: dilutional coagulopathy as a cause of
      surgical bleeding.
AB  - The purpose of this study was: 1) to define coagulation abnormalities in patients
      who receive red cell concentrates rather than whole blood for large volume blood
      loss (greater than 0.5 blood volume); and 2) to determine when coagulation
      abnormalities lead to increased bleeding in the massively transfused surgical
      patient. We studied 32 ASA physical status I or II patients (mean age 15.6 +/-
      2.3 yr) who lost more than 50% of their blood volume during elective posterior
      spinal stabilization. Crystalloid solutions and packed red cell concentrates were
      used to replace blood and fluid losses. Invasive hemodynamic measures, urinary
      output, and serial hematocrit determinations were used to help maintain a
      constant intravascular volume and confirm the estimates of blood loss. The
      quality of hemostasis was assessed during operation. In 15 of the 32 patients,
      surgical hemostasis remained effective throughout posterior spinal fusion. A
      coagulation profile (prothrombin time [PT] and activated partial thromboplastin
      time [aPTT], platelet count, and fibrinogen) was measured at the conclusion of
      operation in these patients. In 17 patients, increased surgical bleeding as a
      result of decreased clot formation and increased bleeding from the wound was
      present. In these 17 patients at the time increased bleeding was diagnosed,
      hemostatic tests (PT, aPTT, fibrinogen, platelet count, and coagulation factor
      assays V, VIII, and IX) were obtained.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7818123
TI  - Safety and feasibility of renal blood flow determination during kidney transplant
      surgery with perfusion ultrasonography.
AB  - Contrast-enhanced perfusion patterns of newly transplanted kidneys were
      determined in 10 patients. Albumin-stabilized sonicated microspheres were
      injected into the iliac-renal artery of the transplanted kidney while continuous
      two-dimensional ultrasound images were recorded. Doppler derived resistance index
      (RI) of the transplanted kidney's blood flow before injection of contrast (0.68
      +/- 0.8) did not differ significantly from RI measured immediately after
      injection (0.72 +/- 0.13) or RI 24 h after surgery (0.69 +/- 0.11). Heart rate,
      mean arterial pressure, central venous pressure, and electrocardiogram (ECG)
      signs for ischemia did not change during contrast injections. Renal scintigraphy
      and renal biopsy revealed acute tubular necrosis and/or rejection in two patients
      at 24-48 h. Videodensitometry was used to assess the ratio of inner to outer peak
      pixel intensity from the recorded tomographic images in six patients. In both
      patients with acute rejection, the inner to outer cortex peak pixel intensity was
      greater than 1, whereas it was less than 1 in the remaining four patients with
      normal postoperative renal function. Visual scores (0-3) of contrast enhancement
      for three doses of Albunex were evaluated (0.5 mL, 1.0 mL, 2.0 mL). Two
      milliliters always enabled perfusion assessment. In seven patients the identical
      dose of Albunex was injected immediately before and 30 s after 2 mg of verapamil
      was injected directly into the renal artery at the time of surgery. The contrast
      enhancement score before verapamil (1.4 +/- 0.6) was significantly less than the
      enhancement score after (2.1 +/- 0.6), implying greater renal blood flow after
      verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7818124
TI  - Monitoring the onset of neuromuscular block at the orbicularis oculi can predict
      good intubating conditions during atracurium-induced neuromuscular block.
AB  - This study was designed to assess whether monitoring the orbicularis oculi (OO)
      can predict good tracheal intubating conditions. Fifty patients, ASA grade I or
      II were studied. Anesthesia was induced with thiopental (5 mg/kg) and fentanyl (3
      micrograms/kg). The ulnar and facial nerves were simultaneously stimulated using
      train-of-four (TOF) stimulations every 10 s. The responses of the adductor
      pollicis (AP) and the OO were estimated visually. Patients were randomly
      allocated to receive either atracurium 0.5 mg/kg (n = 30) or 0.3 mg/kg (n = 20).
      In each group, endotracheal intubation was performed randomly when the OO or the
      AP was completely blocked. If complete block was not obtained, intubation was
      performed 300 s after administration of atracurium. Intubating conditions were
      scored on a 1 to 4 scale. All intubations were performed by the same physician
      unaware of the dose and the muscular responses. After 0.5 mg/kg, both muscles
      were completely blocked in all patients. The average onset time (time from the
      injection of atracurium to the disappearance of all muscular responses after TOF)
      was shorter at the OO (2.35 +/- 0.12 min) than at the AP (3.59 +/- 0.15 min) (P <
      0.001) (mean +/- SD). Endotracheal intubating conditions were comparable in both
      groups: good or excellent after 0.5 mg/kg. After 0.3 mg/kg, complete block was
      achieved only 2/20 at the OO and 12/20 at the AP. Intubating conditions were
      comparable in both groups: poor or inadequate, except in the two patients with
      complete OO block, for whom conditions were good.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7818125
TI  - The influence of the duration of control stimulation on the onset and recovery of
      neuromuscular block.
AB  - The onset of action of atracurium 450 micrograms/kg, mivacurium 160
      micrograms/kg, and vecuronium 80 micrograms/kg was measured after train-of-four
      (TOF) stimulation had been applied for 1, 5, 10, 15, or 20 min in groups of 10
      patients each during anesthesia with thiopental, nitrous oxide-oxygen, and
      fentanyl. TOF stimulation was applied to the ulnar nerve at 2 Hz every 12 s and
      the force of contraction of the adductor pollicis muscle recorded. There was a
      progressive and significant reduction in the time to onset of maximum block with
      increasing times of control stimulation with all three relaxants (P < 0.0001).
      The mean +/- SD times to onset of maximum block decreased from 224 +/- 103 to 73
      +/- 28 s with atracurium, 239 +/- 81 to 101 +/- 33 s with vecuronium, and 198 +/-
      72 to 106 +/- 23 s with mivacurium as the period of control stimulation increased
      from 1 to 20 min. The time to recovery of T1 (first response in the TOF
      stimulation) to 25% of control (duration of clinical relaxation) increased from
      33 +/- 5.7 to 52 +/- 13.4 min with atracurium, 25 +/- 7.6 to 38 +/- 9.4 min with
      vecuronium, and 13 +/- 2.5 to 18 +/- 3.5 min with mivacurium with the period of
      control stimulation increasing from 1 to 20 min. The differences were significant
      for atracurium and vecuronium (P < 0.05-0.0001). We conclude that increasing
      periods of control stimulation are associated with decreasing time to onset of
      neuromuscular block with atracurium, vecuronium, and mivacurium at the adductor
      pollicis muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7818126
TI  - Oxygen saturation in postoperative patients at low risk for hypoxemia: is oxygen
      therapy needed?
AB  - To evaluate the use of oxygen therapy in the immediate postoperative period, 293
      postsurgical patients who had not had thoracic, upper abdominal, or neurologic
      surgery were randomly assigned upon admission to the postanesthesia care unit
      (PACU) to receive: 1) 4 L unhumidified O2 via nasal cannula, 2) 40% oxygen by
      face tent, 3) nurse-coached lung hyperinflations, or 4) no oxygen enhancing
      regimen. Oxygen saturation was measured on all patients at the time of arrival in
      the PACU, after 15 min, and after 30 min in the PACU. Only 11 patients in all
      groups (4%) had their O2 saturation decrease to less than 90% during this time.
      Ten of these had an initial O2 saturation of 92% or less. Significant differences
      in O2 saturation were found at 15 min and 30 min between Groups 1 and 2 which
      received O2 compared to Groups 3 and 4 which did not receive supplemental oxygen.
      The clinical significance of these differences is open to question. Complaints of
      dryness were most common in those receiving unhumidified oxygen by nasal cannula.
      Fourteen percent of patients receiving oxygen by face tent found it uncomfortable
      and complained of nausea. Supplemental oxygen is not essential in maintaining
      adequate oxygen saturation in these PACU patients when oxygen saturation levels
      are more than 92% upon admission to the PACU.

PMID- 7818127
TI  - Alcuronium: a pharmacodynamic and pharmacokinetic update.
AB  - Alcuronium may be considered a muscle relaxant of historical rather than clinical
      significance. However, recent information from the manufacturer revealed its
      persisting clinical use in 26 countries worldwide. Thus, a pharmacodynamic
      pharmacokinetic update appears mandatory. An intravenous (IV) single-bolus
      injection of alcuronium (0.25 mg/kg = ED95) was administered to 10 patients
      undergoing maxillofacial surgery during nitrous-oxide opioid anesthesia.
      Alcuronium neuromuscular block (evoked twitch tension), plasma concentration, and
      renal elimination (high-performance liquid chromatography [HPLC] assay) were
      measured during the 12-h after its administration. The time of onset, the time
      from end of injection to recovery to 25% of control twitch tension (DUR25%), and
      the recovery index were 2.2 +/- 1.2, 54 +/- 14, and 37 +/- 11 min, respectively
      (mean +/- SD). Two hours after the injection of alcuronium, partial recovery from
      the neuromuscular block had occurred from 100% to 26% +/- 24% depression of
      twitch tension, although less than 25% of the injected dose was recovered from
      the urine. The 12-h plasma concentration and urinary recovery were 0.1 +/- 0.08
      mg/L (one-sixth of the 50% inhibitory concentration) and 61% +/- 20%,
      respectively. Recovery from neuromuscular block was dominated by
      intercompartmental distribution rather than by renal elimination. Since
      alcuronium does not undergo biodegradation, our data may serv as a reference for
      the complex pharmacokinetics of readily metabolized modern muscle relaxants. The
      long plasma half-life with slow excretion merits attention with respect to the
      erroneous original perception that alcuronium was an intermediate-acting muscle
      relaxant.

PMID- 7818128
TI  - Can pulmonary aspiration of gastric contents be prevented by balloon occlusion of
      the cardia? A study with a new nasogastric tube.
AB  - Rapid-sequence induction of anesthesia and the application of cricoid pressure
      are the two most common maneuvers performed when patients requiring general
      anesthesia are at risk of pulmonary aspiration. However, these procedures are
      quite elaborate and entail risks and dangers in themselves. A new disposable
      nasogastric balloon tube was developed to prevent the reflux of gastric contents
      by blocking the cardia with a balloon. The effectiveness of this tube was
      investigated in animals and healthy volunteers. In addition, we describe the
      initial experience with the tube during ventilation via a mask in patients with
      an increased risk of aspiration. Twelve pigs with a blocked cardia did not show
      any gastroesophageal reflux under six different procedures to provoke vomiting
      and regurgitation (gastric fluid filling with different volumes, head-down
      positioning, drug-induced vomiting, external gastric compression before and after
      surgical ligation of the pyloric orifice), whereas 37 of 48 provocation maneuvers
      led to a reflux in eight additional pigs with an unblocked cardia. In 26 test
      subjects with a blocked cardia, reflux of gastric contents was not observed when
      vomiting was provoked. After elimination of the cardia blockade, a reflux could
      be triggered in 24 of the 26 subjects. Among 42 patients in danger of aspiration,
      anesthesia could be induced without any problems using a nasogastric balloon tube
      with ventilation via a mask. The present experimental findings in animals and
      test subjects show that the nasogastric balloon tube can prevent gastroesophageal
      reflux under provocation of vomiting and regurgitation.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7818129
TI  - Jet ventilation using fiberoptic bronchoscopes.
AB  - A fiberoptic bronchoscope is used to facilitate tracheal intubation in cases of
      difficult direct laryngoscopy. Occasionally, difficulty is encountered in
      advancing the endotracheal tube after the fiberoptic bronchoscope has been
      introduced into the trachea. This study tested the feasibility of providing jet
      ventilation through the suction channel of the fiberoptic bronchoscope as an
      interim measure under those or similar circumstances. Three commercial models of
      fiberoptic bronchoscopes with suction channels of 1.2-, 1.5-, and 2-mm diameter,
      respectively, were tested in a mechanical test lung at varying compliances and
      resistances using a jet injector connected to an oxygen source at 50 psi. The
      fiberoptic bronchoscope with the 2-mm suction channel was also studied in seven
      adult patients who were anesthetized and paralyzed. Jet ventilation was manually
      performed at the rate of 12/min for 10 min. In the mechanical test lung, the
      tidal volumes with 1.2-, 1.5-, and 2-mm suction channels were as follows: 280 mL,
      490 mL, and 880 mL, respectively, at a compliance of 50 mL/cm H2O and normal
      resistance; 260 mL, 470 mL, and 820 mL, respectively, at a compliance of 50 mL/cm
      H2O and high resistance to simulate bronchospasm; 130 mL, 270 mL, and 890 mL,
      respectively, at a compliance of 20 mL/cm H2O and normal resistance; 120 mL, 220
      mL, and 810 mL, respectively, at a compliance of 20 mL/cm H2O and high
      resistance. In anesthetized, paralyzed patients, oxygen saturation was 96% or
      more throughout the study.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7818130
TI  - Practice policies in anesthesia: a foretaste of practice in the 21st century.

PMID- 7818131
TI  - Cyclic decrease in mixed venous oxygen saturation for the early diagnosis of
      seizure complications after cardiac surgery.

PMID- 7818132
TI  - Tension pneumoperitoneum from tracheal tear during pharyngolaryngoesophagectomy.

PMID- 7818133
TI  - Intraoperative pacemaker malfunction during total hip arthroplasty.

PMID- 7818134
TI  - Myoclonus in the postanesthesia care unit after an intraoperative myelogram.

PMID- 7818135
TI  - Systemic effects of absolute alcohol embolization in a patient with a congenital
      arteriovenous malformation of the lower extremity.

PMID- 7818136
TI  - Continuous spinal analgesia with sufentanil for labor and delivery in a
      parturient with severe pulmonary stenosis.

PMID- 7818137
TI  - Tracheal intubation through tracheoesophageal fistula.

PMID- 7818138
TI  - A hazard of an anesthesia delivery system in a developing country: intraoperative
      subcutaneous emphysema, pneumomediastinum, and cardiac arrest.

PMID- 7818139
TI  - Tracheal intubation in patients with "saber-sheath" trachea.

PMID- 7818140
TI  - Was it the trachea or inadequate tracheal cuff inflation?

PMID- 7818141
TI  - A bedside device to hold the fiberoptic bronchoscope.

PMID- 7818142
TI  - Nasal BiPAP treats hypoxia from postobstructive pulmonary edema.

PMID- 7818143
TI  - Lingular tonsillar hypertrophy and the difficult airway: due regard for practice
      guidelines!

PMID- 7818144
TI  - Laryngotracheal administration of local anesthetics--is the effect mediated by
      systemic absorption?

PMID- 7818145
TI  - Regulatory agencies should reassess all local anesthetics for spinal use.

PMID- 7818146
TI  - Shivering after outpatient arthroscopy.

PMID- 7818147
TI  - A method for percutaneous cannulation for veno-veno bypass during orthotopic
      liver transplantation.

PMID- 7818148
TI  - Combining the fiberoptic bronchoscope with a laryngoscope blade aids teaching
      direct laryngoscopy.

PMID- 7818149
TI  - The alternative use of a patient warming device as a patient cooling device.

PMID- 7818150
TI  - International Anesthesia Research Society 69th Clinical and Scientific Congress,
      Honolulu, Hawaii, March 10-14, 1995. Abstract.

PMID- 7818151
TI  - Digital blood flow response to body warming, cooling, and rewarming in patients
      with Raynaud's phenomenon.
AB  - Although the diagnosis of Raynaud's phenomenon (RP) is usually made easily from a
      careful history, the assessment of RP severity is difficult, for the vasopastic
      attacks are not easily induced under experimental conditions. In this study, the
      laser Doppler flowmetry (LDF) technique was used to quantify digital blood flow,
      which was standardized by body cooling and warming in patients with RP. Twenty
      one healthy subjects and 56 RP patients were studied: 7 had primary RP, 22 had
      suspected secondary Raynaud's syndrome (susp RS), and 27 had systemic sclerosis
      (SSc)-associated secondary Raynaud's syndrome (SSc RS). The inherent variability
      in the acral cutaneous circulation was minimized by whole-body warming and
      cooling. Digital blood flow values at environmental temperatures of 40 degrees C,
      12 degrees C, and after rewarming, to 40 degrees C were recorded, as was the time
      taken for blood flow to reach 25%, 50%, and 75% of the full effects of whole-body
      cooling and rewarming. Patients with primary RP and susp RS had normal blood flow
      values at ambient temperatures of 40 degrees C, 12 degrees C, and after rewarming
      to 40 degrees C when compared with controls, but they had significantly faster
      vasoconstrictor responses to whole-body cooling, suggesting a heightened
      sympathetic activity. Additionally, they had slower vasodilator responses with
      longer 25%max response time to whole-body rewarming. Patients with SSc RS had
      significantly lower blood flow values at 40 degrees C after initial warming and
      following subsequent rewarming, and despite a normal vasoconstrictor response to
      cooling, it took longer for them to vasodilate during rewarming, suggesting that
      poor digital blood flow in these patients may be more related to digital
      vasculature abnormalities and not an increase in sympathetic activity. In
      conclusion, our assessment technique can be used to quantify digital blood flow
      in patients with RP and may be potentially useful in the investigation of the
      etiologic role of the sympathetic nervous system in RP.

PMID- 7818152
TI  - Effect of administration and withdrawal of doxazosin on ambulatory blood pressure
      in patients with essential hypertension.
AB  - The effect of both administration and withdrawal of doxazosin on patients with
      essential hypertension was evaluated by twenty-four-hour ambulatory blood
      pressure (BP) monitoring. Six hypertensive men were treated with doxazosin
      starting at 1 mg/day, and the dosage was titrated at weekly intervals up to a
      maximum of 8 mg/day. The twenty-four-hour BP profile was monitored noninvasively
      before treatment, in the fourth week of treatment, and on days 2 and 7 after the
      discontinuation of doxazosin. The average twenty-four-hour systolic and diastolic
      BPs (SBP and DBP) were lowered by doxazosin treatment and returned to the
      pretreatment levels within two days of doxazosin withdrawal. Doxazosin treatment
      produced a significant decrease in the daytime SBP and DBP but not in the
      nighttime BP values. The daytime BP decrease was no longer detected on days 2 and
      7 after drug withdrawal. The twenty-four-hour pulse rate was not influenced by
      either doxazosin administration or discontinuation. The plasma norepinephrine
      concentration and plasma renin activity were increased by doxazosin treatment and
      were decreased by drug withdrawal. There was no rebound hypertension following
      doxazosin withdrawal. Thus, the present study using twenty-four-hour BP
      monitoring showed that doxazosin treatment reduced the daytime BP in patients
      with essential hypertension and that this reduction was abolished within two days
      after doxazosin discontinuation.

PMID- 7818153
TI  - Raised leg exercises for leg edema in the elderly.
AB  - Leg edema is a common problem in the elderly and requires further evaluation and
      management. METHOD: From October 1990 to July 1992, 245 patients presented to the
      Cleveland Clinic Florida with leg edema. All patients were counseled about the
      benefits of twenty-minute, three-times-a-day raised-leg exercises. Fifty seven
      (57) of the 245 patients were not compliant with this regimen (nonexercise
      group). Although not true controls, they formed a comparison group for those who
      performed the exercise regimen. The exercise group was composed of 188 patients
      with a mean age of 73 +/- 6.8 years, 25 (13%) men and 163 (87%) women; the
      nonexercise group was composed of 57 patients with a mean age of 71.9 +/- 4.3, 19
      (33%) men and 38 (67%) women. Workup for leg edema included: comprehensive
      history, clinical examination including prostate or pelvic examination, complete
      blood count, chemistry profile, thyroid profile, electrocardiogram, chest
      radiograph, and, when indicated, pelvic or leg ultrasound and pelvic computed
      tomographic scan. The circumference of the leg with the maximum amount of edema
      was measured initially and on the fourth week. RESULTS: In this study, the common
      causes of leg edema in the elderly population were venous stasis (63.2%), drug
      induced (13.8%), and heart failure (15.1%). Postphlebitic syndrome, cirrhosis,
      lymphedema, lipedema, prostate carcinoma (CA), and ovarian mass were the less
      frequent findings. Upon comparison of the circumference of leg edema on initial
      visit and four weeks after, both the exercise and nonexercise groups showed
      significant decreases in the measurement of the leg edema (P < .001) except those
      caused by lymphedema.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7818154
TI  - Determinants of left ventricular function two weeks and one year after an acute
      myocardial infarction.
AB  - This study examines possible covariates of left ventricular function two weeks
      and sixteen months after an acute infarction. It was performed in a group of 312
      patients randomized double blindly to recombinant tissue plasminogen activator
      (rt-PA) (n = 156) or placebo treatment and followed thereafter for at least one
      year. Two weeks after the infarction, enzymatic infarct size, infarct-related
      vessel, and number of diseased coronary arteries were significant determinants of
      the infarct-related regional wall motion (centerline method) (R2 = 0.25 to 0.60,
      P = 0.0001). Enzymatic infarct size, regional wall motion of both infarct-related
      and remote areas, reinfarction, and treatment allocation were significant
      independent correlates of ejection fraction (R2 = 0.76), end-diastolic volume (R2
      = 0.20), and end-systolic volume (R2 = 0.69, P < 0.0001). Infarct-related
      coronary artery and predischarge end-systolic volume were significant independent
      covariates of ejection fraction at rest (R2 = 0.47) after sixteen months. Age,
      enzymatic infarct size, and predischarge end-diastolic volume were independent
      determinants of the maximal (R2 = 0.49, P < 0.0001) and peak exercise ejection
      fraction (R2 = 0.49, P < 0.0001).

PMID- 7818155
TI  - Heparin-associated thrombocytopenia (HAT)--still a diagnostic and therapeutical
      problem in clinical practice.
AB  - Type II of heparin-associated thrombocytopenia (HAT) is well known, but the
      cardinal symptom, thrombocytopenia, is rarely adequately considered. Serious and
      potential lethal complications such as pulmonary embolism, cerebral stroke, or
      limb gangrene are often falsely regarded as insufficient anticoagulation. Guided
      diagnosis and therapy are of vital importance for the patient's outcome. Based on
      the experience of patients with HAT Type II treated in the intensive care unit, a
      diagnostic and therapeutic approach to the cardinal symptom thrombocytopenia is
      presented. A recently developed heparin-induced platelet activation assay (HIPAA)
      seems to be a highly sensitive laboratory test. The first therapeutic principle
      in case of presumed and diagnosed HAT is the cessation of unfractioned or low
      molecular-weight heparins. ORG 10172 (Orgaran), a low-sulfated heparinoid with a
      low cross-reactivity (10%) to heparins, can be regarded as the most effective
      anticoagulant in patients with HAT Type II.

PMID- 7818156
TI  - Effects of progressive vascular occlusion on slope and intercept of the pulmonary
      artery pressure-flow relationship.
AB  - Pulmonary hemodynamics may be described by mean pulmonary arterial pressure (PAP)
      cardiac output (CO) plots. The slope of the PAP-CO relationship may define the
      incremental resistance (IR), and the extrapolated pressure intercept (P(I)), the
      effective outflow pressure. The authors investigated the effects of progressive
      pulmonary vascular occlusion on the IR and P(I) of the PAP-CO plot. Nine
      experimental and nine time control dogs were studied. In the former group, PAP-CO
      plots were obtained in three conditions: (1) Baseline, (2) following occlusion of
      the right pulmonary artery, and (3) following occlusion of the right pulmonary
      artery and blood flow to the left upper lobe. Following progressive occlusion,
      there was a corresponding increase in the IR of the PAP-CO plot, from 1.95 to
      3.62 to 5.16 mmHg.1-1.min (all P < 0.05). In contrast to the increase in IR, P(I)
      remained constant. Over the same interval, there were no changes in IR or P(I) in
      the time control group. These findings indicate that changes in the slope of the
      PAP-CO plot correspond to changes in the number of parallel vascular units.

PMID- 7818157
TI  - The effect of a cerebral vasodilator, vinpocetine, on cerebral vascular
      resistance evaluated by the Doppler ultrasonic technique in patients with
      cerebrovascular diseases.
AB  - Changes in cerebral vascular resistance were examined in patients with cerebral
      circulatory diseases by the Doppler ultrasonic technique after administration of
      a cerebral vasodilator, vinpocetine, for two months. Continuous index (CI) and
      pulsatility index (PI) of the blood flow pattern in the internal carotid artery
      were used as objective parameters for changes in cerebral vascular resistance. 1.
      The CI and PI changed significantly after administration of the drug; ie, the CI
      increased while the PI decreased. 2. An inverse correlation was noted between the
      rate of change of the CI (delta CI) and that of the PI (delta PI). 3. The results
      suggest that measurement of the CI and PI by the Doppler ultrasonic technique is
      useful in investigating the effect of drugs on the cerebral circulation.

PMID- 7818158
TI  - Capillary microscopy is a diagnostic aid in patients with acral ischemia.
AB  - The diagnosis of peripheral ischemic diseases is a challenge to the vascular
      specialist, since discrimination of the different entities on clinical grounds is
      not always clear. Capillary microscopy is a noninvasive diagnostic technique that
      can visualize in particular the morphology and perfusion of the digital
      capillaries. The authors investigated all 522 patients who were referred to the
      vascular laboratory over a six-year period, in an attempt to obtain more
      certainty about the diagnosis of their acral ischemic complaints. Patients with
      clinically manifest Raynaud's phenomenon and control subjects were compared to
      obtain differentiation criteria. Thus, capillary microscopy scored a sensitivity
      of 67%, a specificity of 84%, and an accuracy of 81% to detect Raynaud's
      phenomenon. A disturbed capillary morphology was virtually pathognomonic in
      Raynaud's disease secondary to systemic disorders (specificity 100%); the
      accuracy was but 74%. In 69% of the patients with clinically atypical acral
      ischemia, capillary microscopy yielded a diagnosis. Digital blood pressure
      measurements, however, appeared of no use in the diagnosis of Raynaud's
      phenomenon. Hence, capillary microscopy appears to be a useful aid in the
      diagnosis of acral ischemic syndromes.

PMID- 7818159
TI  - Doppler ultrasound in the diagnosis of venous thrombosis.
AB  - Deep vein thrombosis (DVT) has known morbidity and mortality. New noninvasive
      techniques such as B-mode scanning and Doppler ultrasonography (duplex) are
      highly accurate in the diagnosis of this problem but are relatively expensive and
      time consuming. Continuous-wave Doppler, a precursor noninvasive technique, is
      simple, cheap, and easy to perform at the patient's bedside. To test the
      effectiveness of this technique the authors prospectively studied patients with
      clinical suspicion of DVT by Doppler ultrasound and compared the results with
      those from venography. During fourteen consecutive months, patients with a
      clinical suspicion of DVT underwent continuous-wave Doppler examination of both
      inferior limbs. Each case was diagnosed as positive, negative, or inconclusive.
      In addition, the patients underwent a questionnaire regarding risk factors,
      symptoms, and mean relevant physical findings. Doppler examination was blinded to
      venography results. A total of 116 patients with clinical suspicion of DVT were
      examined by Doppler ultrasound. Their mean age was fifty-five years (range:
      eighteen to eighty-eight). There were 57 men and 59 women, and from this group a
      total of 40 patients underwent both Doppler ultrasound examination and venography
      in the course of forty-eight consecutive hours. When cases with an inconclusive
      result were excluded, Doppler ultrasound showed a sensitivity of 89%, a
      specificity of 100%, and an accuracy of 94% for the diagnosis of DVT when
      compared with venography. When a similar analysis was done for the proximal named
      veins, continuous-wave Doppler examination showed a very high specificity and
      positive predictive value and a moderate sensitivity and negative predictive
      value.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7818160
TI  - Lipid profile in the first-degree relatives of patients with precocious coronary
      heart disease in Rohtak area (Northern India).
AB  - Twenty-five patients with precocious coronary heart disease (CHD) (aged forty
      years or less) and 82 first-degree relatives were studied for lipid profile.
      Eighty-eight age- and sex-matched controls were also studied. The mean serum
      cholesterol, triglycerides, low density lipoprotein cholesterol, very low density
      lipoprotein cholesterol, and total cholesterol/high density lipoprotein
      cholesterol of patients and their first-degree relatives were significantly
      higher as compared with normal controls. High density lipoprotein cholesterol
      values were found to be almost identical in the patient group, their first-degree
      relatives, and normal controls. Hyperlipidemia was found in 68% of patients with
      CAD, of their first-degree relatives, and 24% of controls. Almost all lipid
      fractions in relatives of hyperlipidemic patients paralleled those of the
      patients suffering from CHD. Of 25 families studied, 16 had hyperlipidemia. In
      conclusion, it can be stated that there is a statistically significant
      hyperlipidemia in young patients with CHD that has a significant familial
      clustering, thus delineating a group of high-risk individuals (first-degree
      relatives of young coronary patients) for possible primary prevention of CHD.
      This familial clustering could be due to genetic or environmental factors;
      however, the relative contribution of these two factors requires further
      investigation.

PMID- 7818161
TI  - Change of the degree of septal hypertrophy in hypertrophic obstructive
      cardiomyopathy under procainamide treatment. A case report.

PMID- 7818162
TI  - Mitral valve and left ventricular thrombi in an infant with acquired protein C
      deficiency. A case report.
AB  - The authors present an infant with left ventricular and mitral valve thrombi
      diagnosed by cross-sectional echocardiography. Thrombosis was due to acquired
      transient protein C deficiency, which was caused by impaired liver function due
      to sepsis. Because the thombi were very large and mobile, urgent surgery was
      performed. Eight weeks later, the patient's protein C level returned to normal
      ranges. The authors suggest that in all cases with intracardiac thrombosis,
      protein C deficiency should be investigated.

PMID- 7818163
TI  - Genetic analysis of 38XX males with genital ambiguities and true hermaphrodites
      in pigs.
AB  - In pig, the frequency of intersexuality ranges from 0.1 to 0.6%, depending on the
      breed. In a closed pig herd at INRA an intersex condition was observed in 0.75%
      of 'females'. The present study describes 11 animals with a 38XX karyotype and
      the presence of testicular tissue. Phenotypically, all presented with abnormal
      external or/and internal genitalia. Southern blot analysis with Y-specific probes
      (SRY and ZFY) revealed the absence of Y material in all animals tested. By
      polymerase chain reaction (PCR) amplification, 10 of 11 intersex pigs lacked the
      SRY gene in gonad DNA. These data are compatible with an autosomally (or
      pseudoautosomally) determined mechanism. Moreover, analysis of familial cases
      seemed to indicate that 38XX male pseudohermaphrodites and 38XX true
      hermaphrodites may represent alternative manifestations of the same genetic
      defect.

PMID- 7818164
TI  - Identification, isolation and characterization of canine minisatellite sequences.
AB  - A Charomid ordered-array library containing a 2-16 Kb size fraction of MboI
      digested canine genomic DNA has been screened with the Jeffreys multilocus
      probes, 33.6 and 33.15, to identify and isolate canine minisatellite sequences.
      Of the 48 positive clones identified, 7 were found to contain polymorphic
      minisatellites with heterozygosities in the range 20-88%. The majority of the
      remainder were either monomorphic or dimorphic in the animals tested. Analysis of
      intrabreed variation in Bedlington Terriers using two polymorphic minisatellites
      has shown that a significant reduction occurs in the number of alleles seen
      compared to an agglomerated population sample, correlating with the high level of
      inbreeding within this breed. Flanking DNA sequence and partial repeat sequence
      is presented for the most polymorphic minisatellite thus far identified, cCfaMP5.
      The variable region in this minisatellite is similar to human minisatellites
      which show a distinct purine or pyrimidine strand bias.

PMID- 7818165
TI  - Polymorphism analysis of the prion gene in BSE-affected and unaffected cattle.
AB  - Polymerase chain reaction (PCR) primers designed to amplify the octapeptide
      repeat region of the bovine prion gene were used to test the association of
      genotypes with bovine spongiform encephalitis (BSE) in 56 BSE-affected and 177
      unaffected animals. Three alleles (A,B,C) were detected as single-strand
      conformation polymorphisms (SSCPs) and two alleles (1,2--representing six or five
      copies of the octapeptide repeat respectively) were detected as amplified double
      strand fragment length polymorphisms (AMFLPs). Observed genotypes of SSCPs and
      AMFLPs were analysed by chi-square. The SSCP genotypes of nuclear family members
      of animals with BSE and BSE-affected animals were different (P < 0.001, P < 0.01)
      from unrelated animals of the same breed without BSE. No genotypic differences
      were found between the BSE-affected animals and their relatives (P > 0.469). No
      AMFLP genotypic differences were detected between BSE-affected animals, their
      relatives, unrelated animals of the same breed or animals of different breeds (P
      > 0.05). These data suggest that BSE-affected animals and their relatives are
      more likely to have the AA SSCP genotype than unrelated animals of the same breed
      or animals of different breeds.

PMID- 7818166
TI  - Comparative study of pig-rodent somatic cell hybrids.
AB  - The pig chromosome complement of six different types of pig-rodent hybrid cell
      lines was examined by means of fluorescence in situ hybridization with a porcine
      SINE probe. The cell lines were obtained by fusing pig lymphocytes with cells of
      the Chinese hamster cell lines wg3h, BK14-150 and E36, and of the mouse cell
      lines NSO, PU and LMTK-. The hybrids were analysed with respect to: (1) the
      number of pig chromosomes, (2) the type of pig chromosomes, (3) the occurrence of
      pig-rodent chromosome translocations, and (4) the presence of pig chromosome
      fragments. The results show that the number of pig chromosomes varied within and
      among hybrid cell lines. The pig-hamster hybrids mainly retained nontelocentric
      pig chromosomes, whereas the pig-mouse hybrids also retained telocentric pig
      chromosomes. Pig-rodent chromosome translocations were found in all types of
      hybrids, but the incidence was in general low. Chromosome fragments were abundant
      in BK14-150 hybrids, and rare in most other hybrid cell lines. It is concluded
      that the SINE probe is a useful tool to make a preliminary characterization of
      the porcine chromosome complement of pig-rodent somatic cell hybrids. The results
      of this characterization can be used to select hybrids for further cytogenetic
      analysis. Furthermore, our data show that different rodent cell lines will have
      to be used as fusion partners for the production of hybrids when constructing a
      panel informative for all pig chromosomes.

PMID- 7818167
TI  - Molecular heterogeneity for bovine maple syrup urine disease.
AB  - In Poll Herefords, it is known that maple syrup urine disease results from a
      nonsense mutation in codon -6 of the gene for the E1 alpha subunit of branched
      chain alpha-keto acid dehydrogenase. The disease also occurs in Poll Shorthorns,
      but its molecular basis in this breed has not yet been determined. Allele
      specific hybridization and allele-specific amplification, both based on the Poll
      Hereford mutation, failed to detect the mutant allele in Poll Shorthorn
      heterozygotes, and detected the normal allele in affected Poll Hereford-cross
      Poll Shorthorn calves. These results demonstrate between breed molecular
      heterogeneity for bovine maple syrup urine disease.

PMID- 7818168
TI  - Blood groups and protein polymorphisms in five goat breeds (Capra hircus).
AB  - Data on allele frequencies at six red cell blood group systems and three blood
      protein polymorphic loci in five goat breeds are reported. Two blood proteins,
      albumin and carbonic anhydrase, were not found to be polymorphic. The B blood
      group system of goats, like its homologue in cattle and sheep, is highly complex.
      At least 44 B phenogroups (haplotypes) have been distinguished in this study.
      Based on the variation in allele frequencies between breeds, genetic distances
      were calculated. The distances estimated by four different methods were in close
      agreement with data from the history and geographic origins of the breeds
      examined.

PMID- 7818169
TI  - Linkage mapping and partial sequencing of 10 cDNA loci in the chicken.
AB  - Ten cDNA clones derived from chicken spleen cell mRNA have been partially
      sequenced and the genes which encode the mRNAs have been located within the
      linkage map of the chicken genome. The sequences of five of these clones show
      strong homology to known mammalian genes, the remainder show little homology to
      sequence present in the current databases. Interestingly, one of these clones
      appears to be the chicken homologue of the mammalian peptide transporter gene
      TAP2 and is located within the major histocompatibility complex. Two other clones
      are homologous to genes involved in protein synthesis and these are tightly
      linked in chickens, as in mice. These results suggest that partial sequencing and
      mapping of clones from selective cDNA libraries may be an efficient way of adding
      candidate genes to the chicken linkage map and that on a local scale there may be
      some conservation of grouping of genes between chickens and mammalian species.

PMID- 7818170
TI  - Chromosomal assignment of porcine microsatellites by use of a somatic cell hybrid
      mapping panel.
AB  - A well-established and characterized somatic cell hybrid panel was used to map
      three polymorphic microsatellites. Microsatellite S0072, representing the linkage
      group S0007-S0072, was assigned to porcine chromosome 14. Microsatellite S0009,
      representing the unassigned linkage group EAM-S0009-S0071, was assigned
      tentatively to porcine chromosome 11. Finally, S0062 was tentatively mapped to
      chromosome 18. S0062 may represent the first marker for porcine chromosome 18.

PMID- 7818171
TI  - A polymorphic monoclonal anti-BoLA class I antibody.
AB  - Cytotoxic monoclonal antibody IVA 44 was generated after the intraperitoneal
      immunization with peripheral blood mononuclear (PBM) cells and the boost by the
      intrasplenic inoculation of skin graft. The detected membrane antigen isolated by
      immunoprecipitation appears to be composed of two subunits characteristic for the
      MHC class I molecules. The antibody IVA 44 exhibited a different reactivity: it
      recognized the BoLA A14 (A8) specificity in animals typed in the Fifth BoLA
      workshop, while it reacted with all A8 positive animals including subtypes A14
      and A15 in Czech and Slovak cattle. It is concluded that mAb IVA 44 might detect
      the broad subtype of A8 covering A14 and certain A15 split(s). The diverse A15
      reactivity of this mAb in the workshop and our population could be explained by
      the different occurrence of A15 splits in both populations.

PMID- 7818172
TI  - RFLP and linkage analysis of the porcine casein loci--CASAS1, CASAS2, CASB and
      CASK.
AB  - Restriction fragment length polymorphisms (RFLPs) were revealed at the porcine
      casein loci with the following combinations of restriction endonucleases and
      porcine cDNA clones: alpha s1-casein (TaqI); alpha s2-casein (BamHI); and beta
      casein (SacI). These RFLPs were shown to be under simple monogenic control by
      segregation analysis of two- and three-generation families. The CASAS1, CASAS2
      and CASB casein loci were also shown to be linked with no recombinant haplotypes
      observed amongst 77 meioses in Large White and Meishan F1 and F2 crosses. No
      recombinants were observed in a further 106 meioses that were informative for
      linkage between CASAS1 and CASAS2.

PMID- 7818173
TI  - Genetic variation at pig plasma protein locus PLP1 and its assignment to
      chromosome 5.
AB  - A new genetic polymorphism of an unidentified plasma protein (PLP1) in pigs was
      described by using a method of two-dimensional gel electrophoresis and protein
      staining. Two codominant alleles, with frequencies of 0.83 and 0.17, were found
      in the Swedish Yorkshire breed. The PLP1 marker was typed in a three-generation
      pedigree and tested for linkage against a set of 128 markers. The PLP1 locus
      showed significant LOD score values with three different microsatellite markers
      (S0092, DAGK and S0005), previously assigned to chromosome 5.

PMID- 7818174
TI  - Molecular characterization of the porcine MHC class I region.
AB  - A porcine cosmid library was screened with a human MHC class I cDNA. Four
      positive clones were isolated and mapped with different restriction
      endonucleases. Altogether nine SLA class I genes were identified and their
      positions located within restriction maps. Sizes of class I homologous DNA
      sequences varied between 3600 and 5800 bp. The distances between these regions
      ranged from 11,900 to 22,200 bp.

PMID- 7818175
TI  - A rapid protocol for sexing chick embryos (Gallus g. domesticus).
AB  - A method for establishing the sex of chick embryos before the appearance or
      morphological differences between males and females has been developed. DNA was
      isolated from 5-7-day-old embryos by proteinase K digestion and subjected to
      polymerase chain reaction (PCR) amplification with W-chromosome specific primers.
      Sexing can be achieved within 1 day using as little as 1 ng template DNA.

PMID- 7818176
TI  - A new buffer system for acid PAGE typing of equine protease inhibitor.
AB  - A new buffer system for acid PAGE typing of protease inhibitor (Pi) is described.
      This buffer system replaces pyridine and cacodylic acid with L-histidine and MES,
      making the buffer less toxic and less expensive than the acid PAGE system
      commonly used but with no loss of resolution.

PMID- 7818177
TI  - Four new porcine polymorphic microsatellite loci (S0032, S0034, S0036, S0037).

PMID- 7818178
TI  - A polymorphic tetranucleotide repeat in the ovine metallothionein II gene.

PMID- 7818179
TI  - Four polymorphic microsatellite loci for the European wild rabbit, Oryctolagus
      cuniculus.

PMID- 7818180
TI  - An XbaI RFLP at the porcine gelsolin locus (GSN).

PMID- 7818181
TI  - Dinucleotide repeat polymorphism at the bovine MM12E6 and MM8D3 loci.

PMID- 7818182
TI  - HincII and PstI reveal polymorphisms at the porcine orosomucoid (ORM) locus.

PMID- 7818183
TI  - Ovine X-chromosome microsatellites at the OarAE25 and OarAE133 loci.

PMID- 7818184
TI  - ARO62: a bovine polymorphic (AGC)n trinucleotide microsatellite.

PMID- 7818185
TI  - A compound TaqI polymorphism in sheep revealed by a carbonic anhydrase II (CA2)
      probe.

PMID- 7818186
TI  - Fifteen polymorphic bovine dinucleotide microsatellites.

PMID- 7818187
TI  - A panel of RFLP markers from sheep genomic DNA.

PMID- 7818188
TI  - A TaqI polymorphism at the beta-globin (HBB) locus in cattle.

PMID- 7818189
TI  - An anonymous water buffalo probe detects a TaqI RFLP in cattle.

PMID- 7818190
TI  - Polymorphism at the nucleoside phosphorylase (NP) locus in cattle.

PMID- 7818191
TI  - S0306--a molecular marker at pig chromosome 18q24.

PMID- 7818192
TI  - Nine porcine polymorphic microsatellites (S0141-S0149).

PMID- 7818193
TI  - Five polymorphic canine microsatellites.

PMID- 7818194
TI  - [Expected difficult intubation and anesthetic technique].

PMID- 7818195
TI  - [Vigilance for medical devices, a step towards quality assurance].

PMID- 7818196
TI  - [Comparison of the analgesic efficacy of nalbuphine and its combination with
      propacetamol during the immediate postoperative period in gynecologic-obstetric
      surgery].
AB  - This prospective randomized single-blind study compared the efficacy of a
      combination of propacetamol (2 g) and a low dose of nalbuphine hydrochloride (10
      mg) with nalbuphine hydrochloride (20 mg) alone, in a population of 152 white
      female patients after gynaecologic or obstetrical surgery, for alleviation of
      postoperative pain in recovery room. The drugs were administered intravenously in
      case of pain. The population was divided into two groups: group 1 received 20 mg
      of nalbuphine hydrochloride and group 2 received 2 g of propacetamol combined
      with 10 mg of nalbuphine hydrochloride. The pain intensity was studied with the
      visual analogue scale and comparisons use no parametric tests (Mann and Whitney
      test, Kruskall and Wallis test) and Chi2 test. Groups were similar for age,
      surgical and anaesthesia procedures and initial pain level. The propacetamol
      nalbuphine hydrochloride 10 mg association provided a significantly better
      analgesia than nalbuphine 20 mg during the first two postoperative hours (p <
      0.05). In group 1, the analgesia score decrease was respectively 28 +/- 25 mm
      (range: 33-75 mm) after 1 h and 31 +/- 25 mm (range: 26-84 mm) after 2 h. In
      group 2, the decrease was more important: 37 +/- 21 mm (range: 5-84 mm) after 1 h
      and 42 +/- 23 mm (range: 20-84 mm) after 2 h. Side effects were minimal and
      similar in both groups (nausea, drowsiness). It is concluded that a propacetamol
      nalbuphine hydrochloride 10 mg association provides better analgesia than single
      dose of 20 mg of nalbuphine. This association convenient analgesia with a
      decreased dose of nalbuphine.

PMID- 7818197
TI  - [Introducing patient-controlled analgesia in a private hospital].
AB  - Patient controlled analgesia (PCA) is now a well recognized technique for
      postoperative analgesia. This study reports an experience of 24 months with 768
      patients in a French private hospital. The first step was to train the team for
      this new technique. The second step was to agree on standards of prescription and
      safety monitoring rules (respiratory rate plus sedation score), as well as on the
      selection of patients. Analgesia was obtained with self administrated bolus plus
      a constant infusion (0.5 milligram per hour) of morphine in all patients, and in
      some with an addition of paracetamol or ketoprofene for a sparing effect on
      morphine consumption. All patients were returned to their ward, after an initial
      titration of pain treatment in the recovery room. No major problems occurred
      during the study period. In 13 patients the respiratory rate decreased to or
      under 10 c.min-1 without increased sedation and for safety reasons, the PCA was
      discontinued. PCA is now routinely used postoperatively for a majority of painful
      procedures in our institution.

PMID- 7818198
TI  - [In vitro effects of the alkalinization of 0.25% bupivacaine and 2% lidocaine].
AB  - Recent clinical studies have suggested that alkalinization of local anaesthetic
      agents may shorten the onset time and lengthen their duration of action. In
      clinical practice, sodium bicarbonate 1.4 and 4.2% are often added to local
      anaesthetic agents to obtain these effects. We evaluated pH changes of 4 local
      anaesthetic solutions commonly used for obstetrical epidural anaesthesia, in
      order to develop titration curves with sodium bicarbonate 1.4 and 4.2%. Local
      anaesthetic agents tested included lidocaine 2% and bupivacaine 0.25% with and
      without epinephrine. Each one was divided in 10 mL aliquots, and supplemented
      with 25 micrograms of sufentanil (1 mL). The pH measurement were made with a pH
      meter P 500 with a combined electrode (TBC 12/HS) in the standard solution and
      after incremental addition of 0.5 mL of 1.4 or 4.2% sodium bicarbonate. The
      percentage of the free form of local anaesthetic was calculated for each step,
      using the Henderson-Hasselbalch equation. Results showed that alkalinization is
      not beneficial with epinephrine free solutions. Increasing volumes of sodium
      bicarbonate, buffered the acidic effect of sodium bisulfite present in solutions
      containing epinephrine, and increased the percentage of the free form of local
      anaesthetic to the level of epinephrine free solutions. From this pH point
      upwards, the gain is poor and precipitates are generated. This study suggests
      that 1 mL of 4.2% sodium bicarbonate for 10 mL of local anaesthetic solution is
      the best theorical choice for alkalinization of a local anaesthetic associated
      with epinephrine.

PMID- 7818200
TI  - [Value of transcranial Doppler ultrasonography in the management of severe head
      injuries].
AB  - Transcranial doppler ultrasonography (TCD) is a non invasive technique for the
      assessment of cerebral blood flow (CBF). The aim of this prospective study was to
      evaluate the benefit of TCD for the monitoring of major head trauma patients.
      Therefore 10 of such patients, aged 17 to 37 years, had a TCD at admission and
      subsequently at least twice a day. Following data were measured simultaneously at
      the site of the right and the left middle cerebral arteries: the systolic (SV),
      diastolic (DV) and mean (MV) blood velocity, the resistance index (RI) of
      Pourcelot (RI = SV-DV/SV) and the pulsatility index (PI) of Gosling (PI = SV
      DV/MV). Simultaneously, the mean intracranial pressure (ICP) obtained with a
      subarachnoid probe, the PaCO2 and the mean arterial pressure (Pa) were measured.
      The cerebral perfusion pressure (CPP) was calculated with the formula: CPP = Pa
      ICP. A total of 132 measures were analysed. There was a linear relation between
      RI and CPP (r = 0.566; p < 0.001), between RI and ICP (r = 0.822; p < 0.001), as
      well as between PI and CPP (r = 0.563; p < 0.001) and between PI and ICP (r =
      0.837; p < 0.001). In the opposite there was no statistically significant
      relation between ICP and MV (r = 0.18) nor between CPP and MV (r = 0.23).
      However, a MV over 100 cm.s-1 was regularly associated with a ICP over 60 mmHg.
      The close correlation between RI, PI and ICP allows to use RI or PI to estimate
      ICP.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7818199
TI  - [In vitro and in vivo effects of propofol on the hemoglobin dissociation curve].
AB  - This study assessed in vivo and in vitro the effects of propofol on the affinity
      of hemoglobin for oxygen in seven ASA 1 adults. For the in vivo study, venous
      blood samples were withdrawn before and after premedication, after the injection
      of 2.5 mg.kg-1 of propofol and after 15 minutes of maintenance at an infusion
      rate of 0.2 mg.kg-1.min-1. For the in vitro study, propofol was added to the
      blood withdrawn before premedication in order to obtain two samples at a
      concentration of 1 microgram.mL-1 and 2 micrograms.mL-1 respectively. Propofol
      changed neither in vivo, nor in vitro, the P50 and the number of Hill indicating
      the angle of the slope of the dissociation curve, nor in vivo the concentration
      of 2,3-DPG.

PMID- 7818201
TI  - [Value of the cytology of bronchoalveolar lavage in the early diagnosis of
      nosocomial lung infections in patients with thoracic injuries].
AB  - Mechanically ventilated patients, especially those with thorax trauma, suffer
      commonly from nosocomial pneumonia. In these patients, conventional diagnostic
      criteria for bacterial pneumonia may not be completely reliable, as an accurate
      interpretation of the chest radiograph is too difficult. The invasive means for
      the diagnosis of pneumonia (protected specimen brush, bronchoalveolar lavage),
      require 24-48 hours to obtain the results of cultures. Therefore no information
      is available to guide the initial choice of antimicrobial therapy. For some
      authors, the quantification of intracellular bacteria, present in cytocentrifuged
      preparations made from lavage fluid, may provide rapid identification of patients
      with pneumonia. We evaluated the benefit of this type of analysis in thorax
      trauma patients. In 36 patients, 48 samples were taken. With a threshold value of
      10% of cells containing intracellular organisms, microscopic examination had a
      sensitivity and a specificity of 83%. We conclude that this technique may be
      useful for the early diagnosis of nosocomial pneumonia in ventilated thorax
      trauma patients.

PMID- 7818203
TI  - [Proposal for a new multifactor screening score of difficult intubation in ORL
      and stomatognathic surgery: preliminary study].
AB  - This study assessed prospectively in 295 ENT adult patients the predictive value
      of clinical indicators for difficult intubation and of a new multifactorial
      score, established by the allocation of points (0, 3, 5 or 7) depending on the
      degree of presence of seven factors: pathology known to be associated with a
      difficult intubation, clinical signs of airways' pathology, inter-incisors gap
      and mandible's luxation, submental mandibular-thyroid distance, normal or short
      and broad neck, head and neck movements, and Mallampati's test. The incidence of
      difficult laryngoscopy was 14% and the use of particular techniques for tube
      insertion was required in 8% of patients. The presence of malformation or
      pathology often associated with a difficult intubation and the presence of
      functional signs of airways' pathology predict the difficulties of laryngoscopy
      and tracheal intubation with a good sensitivity and specificity. The analysis of
      the "Receiver Operating Characteristic curves" showed that a score higher or
      equal to 11 allows the prediction of difficult intubations with a sensitivity of
      96% and a specificity of 90%.

PMID- 7818202
TI  - [Mesentric venous thrombosis. Risk factors, treatment and outcome. An analysis of
      18 cases].
AB  - Eighteen patients with an acute thrombosis of the splanchnic veins were reviewed.
      Most of apparently idiopathic cases of splanchnic vein thrombosis are related to
      an increased coagulation related to a congenital or acquired defect of
      haemostasis. The aim of this study was to assess the effects of a new and
      effective treatment. Nine male and 9 female patients (range of age: 19 to 81
      years) experienced a mesenteric venous thrombosis. There were 14 mesenteric vein
      thromboses with infarction, two transient mesenteric venous ischaemias without
      bowel infarction and two acute thromboses of the splanchnic veins without bowel
      ischaemia. A coagulopathy was detected in seven patients: oral contraception,
      protein C (PC) or antithrombin III (AT III) congenital deficiencies, acquired
      deficiency of AT III, PC and protein S (PS), polycythaemia in the post-partum
      period and primary myeloproliferative disorder. No coagulopathy was associated
      with thrombosis in eight cases: mesenteric haematoma, splenomegaly, cirrhosis,
      appendicectomy, cholescytectomy, chronic heart failure, treatment with beta
      adrenergic receptor antagonist and digitalis, stenosis of the portal anastomosis
      after liver transplantation. Twelve patients required surgery: eight intestinal
      bowel resections with immediate anastomosis, four resections without immediate
      anastomosis. Only one patient underwent a second look for a repeat bowel
      resection. No death occurred in the early postoperative period and 17 out of 18
      patients were alive after 12 years. An oral anticoagulant therapy was undertaken
      from two months to seven years. However, three patients suffered a recurrent
      thrombosis. Two of them required a long-term anticoagulation. Six patients
      experienced a portal hypertension and oral anticoagulants were discontinued in
      three of them because of bleeding oesophageal varices. Six patients were treated
      only by unfractionated heparin (UFH) or low molecular weight heparin (LMWH)
      followed by oral anticoagulants. After laparotomy, two were only treated with UFH
      without any bowel resection, as mesenteric venous ischaemia was too extensive.
      These observations suggest that the choice between an appropriate medical or
      surgical treatment is important and must be discussed. Since 1989, the
      therapeutic choice has been modified by ultrasonography and contrast enhanced
      computed tomographic scan which confirms diagnosis, allows to follow up and check
      the effects of anticoagulation and to choose the time for surgery. When the
      diagnosis is established and the patient's risk is low, the IU . kg(-1) . d(-1)
      to obtain an antifactor Xa activity between 0.3 and 0.6 antiXa IU mL(-1). When
      the diagnosis is uncertain and the patient's risk if high a laparotomy is
      required.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7818204
TI  - [Arguments for the addition of an oxygen reserve container to the anesthetic
      equipment].
AB  - In France, the presence of an emergency oxygen cylinder as part of every the
      anaesthetic machine is not made compulsory by an official regulation. This
      article provides arguments in favour of such a presence, as recommended by the
      French Society of Anaesthesia and Intensive care (SFAR).

PMID- 7818205
TI  - [Training in anesthesiology and surgical intensive care in the United Kingdom].
AB  - A review of the training in anaesthetics in the United Kingdom is presented.
      After basic medical training and obtaining the MB BS qualification, the trainee
      will usually spend a year outside anaesthetics. Following this period, basic
      specialist training takes approximately four years, going through senior house
      officer and registrar grades, leading to the Fellow of the Royal College of
      Anaesthetist (FRCA) diploma. It is a three part examination system: Part 1 tests
      fundamentals of clinical practice, Part 2 tests the applied basic sciences
      relevant to anaesthesia and in Part 3 candidates are examined in the full range
      of knowledge required from the specialist anaesthetist. A Certificate of
      Accreditation is awarded after three years of satisfactory experience in a senior
      registrar post. The accredited senior registrar is then ready to apply for a
      consultant vacancy or a senior lecturer's post. Academic appointments are made at
      registrar and senior registrar levels (lecturers) and consultant level (as senior
      lecturers and professors).

PMID- 7818207
TI  - [Anesthesia for laparoscopic surgery in pediatrics].
AB  - The increasing use of laparoscopic surgery in children is associated with the
      enlargement of the spectrum of indications to appendicectomy, extramucosal
      pylorotomy and cure of oesophageal reflux. It is also linked with new problems,
      mainly due to physiologic modifications elicited by pneumoperitoneum and
      patient's posture. Although sufficient data are not yet available, the
      respiratory and cardiovascular modifications are probably similar to those
      occurring in adults, at least in children more than 4-month-old, as long as the
      intra-abdominal pressure remains under 15 mmHg. The use of higher intra-abdominal
      pressures has not been reported in children. In this case, the cardiovascular
      changes consist mainly in an increase in arterial pressure. In some children, non
      specific decreases in heart rate and in blood pressure can be observed. The
      latter can be elicited by a surgical complication, hypovolaemia, head-elevated
      position or deep anaesthesia. In the newborn and infant under 6 months, intra
      abdominal pressures of 15 mmHg or more carry a risk of low cardiac output due to
      a decrease in contractility and compliance of the left ventricle. In this group
      of age it is therefore recommended to establish a pressure not higher than 6
      mmHg. Moreover, in these very young children, the risk for reopening of the right
      left shunts can result in heart insufficiency and systemic gas embolism.
      Peroperative respiratory changes include an increase in PetCO2 and more rarely a
      decrease in SaO2. The interpretation of the former depends on the site of gas
      sampling in the anaesthetic system. It is easily controlled by an increased
      minute ventilation. Various causes, such as bronchial intubation, inhalation of
      gastric contents or gas embolism, can decrease SaO2. Contra-indications for
      laparoscopic surgery include hypovolaemia, heart diseases, increased intracranial
      pressure and alveolar distension. Therefore newborns are patients at high risk in
      so far as their foramen ovale or their ductus arteriosus is patent, the pulmonary
      arterial resistances remain increased and a bronchodysplasia is existing. In some
      cases a special disease is often associated. As an example recurrent bronchitis
      or asthma is associated with an oesophageal reflux and a sickle-cell disease in
      patients with cholelithiasis. These patients require special pre-, per- and
      postoperative care for prevention of complications. Anaesthesia for laparoscopic
      surgery does not require a major extension of the usual security regulations.
      Special attention must be paid to arterial pressure. Therefore end-expiratory
      concentration of the halogenated anaesthetic agent should not be kept higher than
      1.5 times the MAC related to the age during maintenance of anaesthesia.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7818206
TI  - [Anesthesia in surgery for intracranial aneurysms].
AB  - The two major neurological complications of subarachnoid haemorrhage (SAH) due to
      an intracranial aneurysm are rebleeding and delayed cerebral ischaemia related to
      cerebral vasospasm. The best way to prevent rebleeding is early surgery. Even
      when surgery is performed within the first 72 hours posthaemorrhage, the risk of
      cerebral ischaemia due to vasospasm is high. Conventional medical treatment of
      cerebral vasospasm includes haemodilution, hypervolaemia and increase of arterial
      blood pressure. Haemodilution is of limited value as the patients suffering from
      SAH have usually a low haematocrit. The effectiveness of hypervolaemia is
      controversial and it may worsen cerebral and pulmonary oedema. Systemic
      hypertension is an effective therapy of vasospasm, but which can only be used
      once the aneurysm is controlled. Nimodipine and nicardipine, two calcium
      antagonists, have a beneficial effect on neurologic outcome following SAH. Today,
      it is still debated whether the beneficial effect of nimodipine results from the
      vascular effect of the drug or from a direct cerebral cytoprotective mechanism.
      Early surgery implies that surgeons operate on brains in acute inflammatory
      state. Thus, it is mandatory to use peroperative techniques improving cerebral
      exposure. These techniques include infusion of mannitol, lumbar cerebrospinal
      fluid (CSF) drainage, administration of anaesthetic agents known to decrease
      cerebral blood flow (CBF) and hypocapnia. Usually, the effect of CSF drainage is
      very effective and sufficient by itself. The second objective in the peroperative
      period is to avoid ischaemia. In areas with decreased flow distal to vasospasm,
      autoregulation is impaired and CBF is directly dependent on cerebral perfusion
      pressure. Furthermore, the safe practice of transient clipping of vessels
      supplying the aneurysm has dramatically reduced the indications of controlled
      hypotension. During temporary clipping, some authors recommend a pharmacological
      brain protection using barbiturates, etomidate or propofol, but this practice has
      not been validated by randomized studies. However, it is generally agreed that
      the arterial pressure should be increased during temporary clipping to improve
      collateral blood flow and to maintain it after the aneurysm has been secured. To
      conclude, together with lumbar CSF drainage and transient clipping, the
      anaesthetic management of the patients should include: maintenance of the
      arterial blood pressure close to its preoperative level, maintenance of PaCO2
      between 30 and 35 mmHg and of normovolaemia through replacement of fluid and
      blood losses. After completion of surgery, recovery from anaesthesia should be
      rapid to allow fast diagnosis of neurological complications. The monitoring of
      the status of consciousness is the key of the diagnosis of early postoperative
      complications.

PMID- 7818208
TI  - [Intrapleural analgesia].
AB  - Interpleural analgesia, a recently devised method for postoperative analgesia,
      consists of the injection of a local anaesthetic into the pleural space. The
      technique of the catheter insertion is simple and derived from the threadening of
      an epidural catheter, using the same equipment. An unilateral analgesia is
      obtained with a rapid onset but not efficient enough for a surgical procedure.
      The area covered by analgesia includes the thorax and the upper part of the
      abdomen. No haemodynamic adverse effects occur and ventilatory function is rather
      improved. The main mechanism of analgesia is probably a retrograde intercostal
      nerve blockade. Although the exact dose and volume of local anaesthetic is still
      controversial, 20 to 30 mL of 0.5% bupivacaine is very likely the most
      convenient. Lidocaine may also be administered at the dose of 2 mg.kg-1 of a 2%
      solution. Main indications of interpleural analgesia are cholecystectomies and
      thorax trauma patients. Adverse effects and hazards are uncommon and include
      mainly pneumothorax and toxic effects of a local anaesthetic overdose.

PMID- 7818209
TI  - [Treatment of acute colonic pseudoobstruction (Ogilvie's syndrome) by cisapride].
AB  - A case is reported of a 68-year-old woman admitted in the ICU for acute
      exacerbation of a chronic obstructive respiratory disease. The trachea was
      intubated and the lungs ventilated mechanically. She received sedation including
      midazolam and phenoperidine 1 mg.h-1. On the 6th day, she experienced a massive
      colonic dilation (caecal diameter of 10 cm at X-ray examination). A colonoscopy
      was performed which showed the absence of obstruction, confirmed the diagnosis of
      pseudo-obstruction of the colon and allowed a decompression which was
      inefficient. A new colonoscopic decompression was performed on the 8th day,
      without prolonged effect. At that time, the patient was given cisapride in her
      gastric tube (80 mg). This treatment restarted the bowel movements within 48
      hours and the caecal diameter decreased immediately to 7 cm. Cisapride was
      maintained for 10 days and mechanical ventilation for 30 days. No further
      dilation occurred during this time and the patient was discharged from the ICU.
      Few cases of Ogilvie's syndrome successfully treated with cisapride have been
      reported in the literature. The efficacy of this agent for the treatment of
      Ogilvie's syndrome remains to be assessed in a controlled study.

PMID- 7818210
TI  - [Acute silicosis caused by intentional inhalation of scouring powder].
AB  - A case of acute silicosis due to intentional inhalation of the scouring powder
      Ajax in a female patient suffering a sickle-cell trait (30% of S haemoglobin) is
      reported. It consisted of an acute immuno-allergic pneumonitis with fever and a
      respiratory distress syndrome. It was associated with a severe biological
      inflammatory syndrome and immunological disturbances with circulating immune
      complexes and antinuclear antibodies. The assessment of respiratory function
      demonstrated the presence of a restrictive syndrome with hypoxaemia and decreased
      CO transfer. The anatomopathological and mineralogical exams confirmed the
      diagnosis of silicosis and elicited birefringent particles in polarized light,
      some nodules, interstitial fibrosis and proteic deposits in favour of alveolar
      lipoproteinosis. The treatment included mechanical ventilation with PEEP,
      antibiotics and corticosteroids. Two pulmonary lavages were performed. The
      patient died of septic shock before a lung transplantation could be obtained.

PMID- 7818211
TI  - [Thrombosis of the right atrium disclosed by severe pulmonary embolism].
AB  - The case of a thrombosis of the right auricle, revealed by severe pulmonary
      embolism in a 56-year-old patient without significant medical history is
      reported. He was admitted to the ICU with a haemorrhagic cerebrovascular
      accident. The course was characterized by the occurrence of a venous thrombosis
      of the right lower limb confirmed by phlebography. The treatment with a platelet
      antiaggregating agent was effective and the patient left hospital two weeks
      later. He was re-admitted after 2 months with a clinical picture of massive
      embolism including polypnea, tachycardia and haemoptysis. The diagnosis was
      confirmed by pulmonary angiography (Miller index > 65%) and echocardiography
      showed a floating thrombus in the right auricle with dilated right cavities. The
      phlebocavography displayed an extensive thrombosis in the left lower limb up to
      femoral, iliac and cava inferior veins. The patient was treated with heparin (500
      IU.kg-1.d-1) and later with antivitamine K. The course was favourable. This is a
      rare case of extensive thrombosis, completely regressive with a treatment
      including only heparin.

PMID- 7818212
TI  - [Arterial embolism caused by an intra-aortic thrombus or a patent foramen ovale?
      Diagnosis by transesophageal echocardiography].
AB  - This case report demonstrates the value of transoesophageal echocardiography
      (TOE) in comparison with transthoracic echocardiography as it allows a better
      view of the thoracic aorta, the auricles, the interauricular septum and the
      cardiac valves, especially in the intubated and ventilated patients. A 84-year
      old woman was admitted to the ICU for hypoxia after carotid-subclavian bypass
      surgery for acute ischaemia of the left upper limb. The TOE showed a dilated
      right heart and a patent foramen ovale, compatible with pulmonary embolism as
      well as two thrombi in the aortic arch. The patient died on the 8th postoperative
      day from refractory hypoxia. the autopsy confirmed the pulmonary embolism and the
      intraaortic thrombi. It is concluded that TOE, readily feasible is indicated in
      case of hypoxia, shock and systemic embolism without cause immediately
      recognizable, especially in ventilated patients.

PMID- 7818213
TI  - [Rhabdomyolysis after prolonged surgical procedure in the lithotomy posture].
AB  - Case report of an obese patient who suffered a bilateral rhabdomyolysis after
      major abdominal surgery under general anaesthesia combined with thoracic epidural
      analgesia. The patient was in the lithotomy position during the ten hours time
      period of the surgery. As the patient was sedated in the intensive care unit, the
      diagnosis was made more difficult. Clinical signs consisted of pain, oedema and
      neurosensitive deficit in both legs. Creatinine kinase plasma concentration was
      increased. Treatment included fluid infusions and fasciotomy. The sequelae were
      major and consisted mainly in muscular deficiency of both legs. This complication
      is favoured by prolonged surgery and muscular compression elicited by non
      physiological positions.

PMID- 7818214
TI  - [An unusual cause of "post-critical" coma].

PMID- 7818215
TI  - [Contribution of laparoscopy to the diagnosis of right diaphragmatic rupture].

PMID- 7818216
TI  - [Pulmonary pasteurella infection with fatal outcome].

PMID- 7818217
TI  - [Sub-coracoclavicular approach of the axillary vein. Apropos of 233 trials].

PMID- 7818218
TI  - [Anti-shock trousers in anaphylactic shock].

PMID- 7818220
TI  - [Reflection on the logo of the French Society of Anesthesia and Intensive Care
      and the "golden number"].

PMID- 7818219
TI  - [Apropos of a case of circulatory assistance in chloroquine poisoning].

PMID- 7818221
TI  - Psychoneuroimmunology. The interface between behavior, brain, and immunity.
AB  - Psychoneuroimmunology is the study of interactions between behavior, the brain,
      and the immune system. This article is designed to provide an overview of this
      new field for the general psychologist. The existence of bidirectional
      communication pathways between the brain and the immune system and the
      implications of this network for behavior are emphasized. Implications are that
      behavioral-psychological processes ought to be capable of altering immune
      function and that events that occur as part of immune responses should modulate
      behavior. Evidence for influences in both of these directions is reviewed. The
      discussion of psychological modulation of immunity focuses on classical
      conditioning and stress, whereas that of immune modification of behavior
      highlights behavioral effects produced by substances released by the immune
      system. Finally, the adaptive role that such changes might play is considered.

PMID- 7818222
TI  - Cost analysis and HIV prevention interventions.

PMID- 7818223
TI  - NIDA's HIV prevention programs.

PMID- 7818225
TI  - On the new call for HIV prevention research.

PMID- 7818224
TI  - CDC behavioral interventions.

PMID- 7818226
TI  - [Three cases of matricide].
AB  - The matricide is defined as the murder of the mother by her son or her daughter.
      The term of parricide is also used. Matricide is not a specific mental disease.
      The study of three original cases leads to classify two of them as psychiatric
      disorders, legal authority is applicable to the last. The first category contains
      a wide spectrum of psychiatric diagnosis and could be successfully controlled by
      treatment. Those cases fall in the article 64 of the French Law at the moment of
      the murder. The second category consists of perverse individuals responsible of
      their actions and hardly curable by treatment. These cases are abandoned to
      Justice. The "parricide" represents 2.54% of murders, the matricide 0.68%.

PMID- 7818227
TI  - [Depression in the aged patient: bibliographic review].
AB  - The purpose of this review is to describe the diverse aspects of depression in
      the elderly. The bibliographical research includes epidemiology, theoretical
      models, diagnosis and treatment. Many studies emphasize the need for an accurate
      diagnosis, given the risk of unrecognized depression. The therapeutic trial is
      used when there is uncertainty about the diagnosis, especially whether it is
      depression or dementia. A treatment and a long follow-up are necessary to prevent
      relapses and recurrences.

PMID- 7818228
TI  - [Effects of neuroleptics on the frontal functions of schizophrenics].

PMID- 7818229
TI  - [Bisexuality in Rembrandt].
AB  - According to the analysis of his painting, "The return of the prodigal son",
      Rembrandt represented the concept of bisexuality. Bisexuality came back with the
      Psycho-analysis. We propose an hypothesis about the periodical repression's of
      this concept.

PMID- 7818230
TI  - [Spiritual themes in mental pathology. Methodical approach].
AB  - The meaning of the themes with spiritual connotations poses complex problems for
      psychiatry, because these themes induce the observer to project his own
      convictions and frames of references on his investigations. A double detachment
      (objectivation) concerning both the object of study and the observer is implied.
      This makes it possible to study these phenomena by a more rigorous method, to
      investigate the conditions of their formation and to demonstrate objectifiable
      correlates (experienced space and time, the various levels of psychic experience,
      factors in the environment...). In consequence the appropriate medical behaviour
      can be more precisely delineated.

PMID- 7818231
TI  - [Development of long term memory in the child].
AB  - The relatively recent development of research on memory has considerably improved
      knowledge on the subject. The cognitive approach allowed to consider memory as a
      multiform phenomenon, implicating separate processes and based on independent
      systems. Memory presently appears as an active process, beginning to get
      organized as soon as the first interactions between child and environment. Recent
      research data show that infants memory seems to present specific characteristics,
      different from those of older subjects. This is a further argument to the theory
      of independent mnemonic systems, growing at different periods of development.

PMID- 7818232
TI  - [Short term memory and severe language disorders in the child].
AB  - Memory, and particularly short-term memory or "working memory" (Baddeley), is
      involved in language acquisition in children. We have studied short-term memory,
      with verbal-and non verbal tests, of 8 children suffering from developmental
      dysphasia compared with other ones, matched in terms of age and performance I.Q.
      (W.I.S.C.-R.). The digit span did not significantly differ in the two groups,
      while the visuo-spatial span was lower in the dysphasic group. The memorization
      of a list of monosyllabic words by dysphasic children was poor in the absence of
      visual presentation and improved by it. Differences between dysphasic and control
      children are unlikely to be due to speech rate which does not significantly
      differ from one group to the other one. The results suggest the existence, in
      language disordered children, of cognitive functions disorders much more
      important than those directly involved in the speech production.

PMID- 7818233
TI  - [Liaison psychiatry at Saint-Dizier General Hospital. 17-year experience].
AB  - Reflexions and studies about the "Psychiatrie de Liaison" at the general Hospital
      of Saint-Dizier, about consultations in psychiatry. Follow up of the
      consultation. Statistical view. Liaison general physician-psychiatrist-family
      physician.

PMID- 7818234
TI  - A practical cytogenetic protocol for in vitro cytotoxicity and genotoxicity
      testing.
AB  - In vitro cytogenetics has been established as a valid method for evaluating the
      genotoxic potential of chemical agents. Armstrong et al have described a simple,
      quantitative approach to in vitro cytotoxicity and genotoxicity testing by using
      Chinese hamster ovary (CHO) cells. This approach can also be sensitive and
      repeatable in an inter-laboratory setting, a prerequisite for routine testing of
      compounds suspected of having genotoxic properties. In the present study,
      cytotoxicity was evaluated by the parameter of mitotic index (MI). Genotoxicity
      is measured by the chromosome aberration (Abs) assay as described by Armstrong et
      al using CHO cells. The basic analytic principles proposed were extended to
      include human lymphocytes. Sister chromatid exchange (SCE) analysis was used to
      establish an additional endpoint. Mitomycin C (MMC), an established clastogen,
      was used as the model compound for protocol validation. Dose response curves for
      MI and Abs in CHO cells were found to be consistent with those reported by
      Armstrong et al. Results from our extended study on lymphocytes and using SCE
      analysis were analogous. Our experience is that this standardized approach is
      indeed sensitive and reliable and can serve as a basis for an inter-laboratory
      testing program.

PMID- 7818235
TI  - When to transfuse blood in sickle cell disease? Lessons from Jehovah's Witnesses.
AB  - Hemoglobin concentration of 7 to 8 g/dl has been considered an indication for
      transfusion in the general adult population and has also been frequently applied
      to patients with sickle cell disease (SCD). Through a review of the case
      histories of two patients with SCD who were also Jehovah's Witnesses and
      developed severe anemia, and considering as well the clinical characteristics of
      this population and the basic physiology of oxygen transport, the appropriateness
      is questioned of this transfusion "trigger" in patients with SCD. It is suggested
      for the latter that a Hb of 5.5 g/dl be used as an indication for transfusion
      except in very specific clinical circumstances.

PMID- 7818236
TI  - A comprehensive scheme for the systematic investigation of hemolytic anemia.
AB  - A comprehensive scheme for the systematic investigation of hemolytic anemia is
      proposed. In addition to routinely available tests for the diagnosis of hemolytic
      anemia, investigation of hemoglobin, analysis of red blood cell membrane
      proteins, and a complete panel of red blood cell enzyme measurements were
      included. The adoption of red blood cell enzyme measurements to routine use was
      facilitated by the automation of these procedures. The resolving power of sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) procedure provided
      a tool for the identification of abnormalities in the red blood cell membrane
      proteins. Such a comprehensive scheme was instrumental in systematically
      identifying and confirming 48 cases of hemolytic anemia which otherwise would
      have escaped detection during the period October 1990 to September 1993 in our
      institution (Fukuoka University Hospital).

PMID- 7818238
TI  - On the clinical significance of the S-phase fractions of tumors.
AB  - The S-phase fraction of a tumor cell population is often viewed as a general
      indicator of the clinical aggressiveness of that tumor. Actually, the S-phase
      fraction of a cancer should be interpreted as no more than an indicator of the
      mean duration of its mitotic cycle. The S-phase fraction of a solid tumor is
      difficult to measure accurately, but in principle it is a powerful predictor of
      the duration of the recurrence-free interval. However, since the duration of the
      mitotic cycle does not correlate with malignancy, the S-phase fraction cannot be
      used to diagnose malignancy. It is of little value in making therapeutic
      decisions because the duration of the mitotic cycle is not a predictor of
      invasion and metastasis.

PMID- 7818237
TI  - Tyrphostin 47 nonenzymatically decarboxylates [1-14C]-pyruvate.
AB  - Tyrphostins inhibit tyrosine kinases and have little effect on the activity of
      serine/threonine kinases. Pyruvate dehydrogenase kinase inactivates pyruvate
      dehydrogenase by phosphorylating serine residues within the multienzyme complex.
      This serine/theronine kinase represents a new family of protein kinases, and one
      (tyrphostin 47) of two tyrphostins tested appeared to activate the pyruvate
      dehydrogenase kinase as determined by [1-14C]-lactate oxidation to 14CO2.
      Experiments designed to determine if the tyrphostins altered pyruvate
      dehydrogenase activity in mitochondria prepared from rat epididymal adipocytes
      using [1-14C]-pyruvate as the substrate demonstrated a dose dependent increase in
      enzyme activity in the presence of tyrphostin 47, but not in tyrphostin 23. This
      apparent stimulation of pyruvate dehydrogenase activity was attributed to
      tyrphostin 47's ability to nonenzymatically decarboxylate [1-14C]-pyruvate, the
      substrate for the pyruvate dehydrogenase assay. Neither tyrphostin directly
      altered pyruvate dehydrogenase kinase activity. Therefore, assays utilizing [1
      14C]-pyruvate and tyrphostin 47 are subject to analytical interference.

PMID- 7818239
TI  - In situ amplification: detection of target sequences in whole tissues.
AB  - Using the polymerase chain reaction (PCR) specific gene target sequences can be
      routinely amplified from isolated nucleic acids. However, this does not allow the
      investigator the option of correlating the presence of amplified product with
      cellular localization. When PCR is performed in situ and coupled with either a
      direct or indirect method of detecting amplified product, a powerful
      investigative tool exists. Owing to variability in results, the features of in
      situ PCR which are most likely to contribute to these effects are described. Also
      described is an amplification chamber for localized in situ amplification (LISA)
      which utilizes tissue culture cloning rings and allows for the amplification of
      gene target sequences in specific regions of paraffin-embedded tissue sections.

PMID- 7818240
TI  - Medullary thyroid carcinoma metastatic to breast masquerading as infiltrating
      lobular carcinoma.
AB  - Metastatic tumors to the breast from an extramammary site are rare entities and
      may present diagnostic difficulties for the surgical pathologist because of
      frequent histological similarities to primary neoplasms in this location. A case
      is reported of medullary thyroid carcinoma metastatic to the breast in a 28-year
      old woman with a family history of MEN IIA (Sipple's) syndrome. Histological
      features resembled infiltrating lobular carcinoma and included the so-called
      "targetoid" and "Indian file" patterns. Immunostaining revealed the true nature
      of the lesion and was diffusely positive for calcitonin, chromogranin, and
      carcinoembryonic antigen. Electron microscopy disclosed typical neurosecretory
      granules confirming the diagnosis. A brief review of the literature and
      differential diagnosis is also presented.

PMID- 7818241
TI  - Amyotrophic lateral sclerosis immunoglobulins increase Ca2+ currents in a
      motoneuron cell line.
AB  - The sporadic form of amyotrophic lateral sclerosis (ALS) is an idiopathic and
      eventually lethal disorder causing progressive degeneration of cortical and
      spinal motoneurons. Recent studies have shown that the majority of patients with
      sporadic ALS have serum antibodies that bind to purified L-type voltage-gated
      calcium channels and that antibody titer correlates with the rate of disease
      progression. Furthermore, antibodies purified from ALS patient sera have been
      found to alter the physiologic function of voltage-gated calcium channels in
      nonmotoneuron cell types. Using whole-cell patch-clamp techniques,
      immunoglobulins purified from sera of 5 of 6 patients with sporadic ALS are now
      shown to increase calcium currents in a hybrid motoneuron cell line, VSC4.1.
      These calcium currents are blocked by the polyamine funnel-web spider toxin FTX,
      which has previously been shown to block Ca2+ currents and evoked transmitter
      release at mammalian motoneuron terminals. These data provide additional evidence
      linking ALS to an autoimmune process and suggest that antibody-induced increases
      in calcium entry through voltage-gated calcium channels may occur in motoneurons
      in this disease, with possible deleterious effects in susceptible neurons.

PMID- 7818242
TI  - The CYP2D6B mutant allele is overrepresented in the Lewy body variant of
      Alzheimer's disease.
AB  - Approximately one-fourth of neuropathologically confirmed cases of Alzheimer's
      disease (AD) also have brainstem and neocortical Lewy bodies, constituting a Lewy
      body variant of AD. Because Lewy bodies are a pathologic hallmark of Parkinson's
      disease (PD), this subpopulation of AD subjects may have the same risk factors as
      PD subjects. Analyses of the cytochrome P450 CYP2D6-debrisoquine 4-hydroxylase
      mutant B allele, a susceptibility gene for PD, revealed a higher representation
      of this allele in the Lewy body variant of AD than in pure AD or non-AD without
      Lewy bodies.

PMID- 7818243
TI  - Chronic relapsing axonal neuropathy: a first case report.
AB  - A relapsing and remitting axonal polyneuropathy developed in a woman at age 47.
      Serial electrophysiological studies showed that the amplitudes of compound muscle
      action potentials and sensory action potentials were reduced but conduction
      velocities were only mildly slowed. F wave latencies were normal and there was no
      evidence of conduction block. Two sural nerve biopsy specimens showed changes
      supportive of axonal neuropathy. Repeated responses to prednisolone alone and
      later prednisolone and azathioprine suggested that inflammatory, possibly
      autoimmune, processes were important in this case of chronic relapsing axonal
      neuropathy.

PMID- 7818244
TI  - Apolipoprotein E genotypes and Alzheimer's disease in a community study of
      elderly African Americans.
AB  - As part of a community-based study of Alzheimer's disease (AD) in the African
      American population age 65 and over, we have determined apolipoprotein E (Apo E)
      genotypes in 85 subjects (31 AD patients and 54 controls). The epsilon 4 allele
      of Apo E was strongly associated with AD in this population sample. The epsilon 4
      allele frequency in AD patients was 40.3% compared with 13.9% in the control
      group, and 22.6% of the AD patients were homozygous for this allele compared with
      3.7% of the control subjects (p = 0.01). This study extends the association of
      Apo E-epsilon 4 and AD to nonwhite populations and provides further evidence that
      the observed allelic association is biologically relevant.

PMID- 7818245
TI  - Drenching sweats as an off phenomenon in Parkinson's disease: treatment and
      relation to plasma levodopa profile.
AB  - We followed 4 patients with Parkinson's disease and severe, intermittent,
      drenching sweats. One patient was studied with serial plasma levodopa levels and
      simultaneous clinical examinations. She was observed during a severe sweating
      episode; this was associated with subtherapeutic plasma levodopa levels (low dopa
      state). All 4 patients' sweats responded favorably to the institution of agonist
      therapy. Drenching sweats should be considered part of the spectrum of off-period
      levodopa-related fluctuations in Parkinson's disease.

PMID- 7818246
TI  - Temporal lobe epilepsy caused by domoic acid intoxication: evidence for glutamate
      receptor-mediated excitotoxicity in humans.
AB  - We describe the development of temporal lobe epilepsy in an 84-year-old man who
      had suffered domoic acid intoxication. Following intoxication he had nausea,
      vomiting, confusion, and coma. Generalized convulsions and complex partial status
      epilepticus progressively developed. After 3 weeks he improved and was seizure
      free with severe residual memory deficit. Electroencephalograms initially showed
      periodic epileptiform discharges, later evolving to epileptic abnormalities over
      frontotemporal regions with diffuse slow waves. Eight months after the
      intoxication the electroencephalogram was normal. One year after the acute
      episode, complex partial seizures developed. Electroencephalograms showed
      epileptic discharges independently over both temporal lobes, with left-sided
      predominance. Magnetic resonance imaging revealed a hyperintense T2-weighted
      signal and atrophy of both hippocampi; a positron emission tomographic scan
      showed bitemporal decreased glucose metabolism. Pneumonia developed and the
      patient died 3 1/4 years after the intoxication. Autopsy disclosed severe
      bilateral hippocampal sclerosis. The seizures following acute domoic acid
      intoxication, the postmortem pathology, and the fact that temporal lobe epilepsy
      developed 1 year after intoxication indicate that the human hippocampus is also
      vulnerable to kainate receptor excitotoxicity, and provide strong evidence
      supporting the role of excitotoxic injury in epileptogenesis. This report
      provides a unique human parallel to, and validates the animal model of, kainate
      induced epilepsy as an important tool for studying temporal lobe epilepsy.

PMID- 7818247
TI  - Staggering gait in medical history.
AB  - Drunkenness and senility were recognized early as the basis of a staggering gait.
      To these were added venereal excesses, hence syphilis. Medical and scientific
      concerns began to be focused on "locomotor ataxia" in the 19th century with the
      systematic development of neuroanatomy and physiology. Rolando and Flourens were
      followed by Romberg and Todd, and later Friedreich, who all gave the spinal cord
      temporal precedence as a culprit over the cerebellum--and there were some
      forerunners. New spinal sensory pathways were delineated by Goll, Flechsig, and
      Gowers. In France, we must specially credit Duchenne as well as Bouillaud, and
      later Babinski, Marie, and Dejerine, for correcting, differentiating, extending,
      and underpinning current concepts. Failures of input and output, of conduction
      and central coordination were invoked and explained, among them the vestibular
      apparatus, as well as the causation by neoplasms, demyelination, degeneration,
      and infarction affecting even the frontal lobe, thalamus, and basal ganglia.
      Clinical testing was brought up to 20th-century standards essentially by
      Sherrington and Barany, followed by Dandy, the neurosurgeon who showed how to
      replace ventricular fluid by air, more recently made obsolete by modern
      roentgenographic procedures. And tabes dorsalis, once the chief culprit, has
      practically become a medical anachronism thanks to penicillin.

PMID- 7818248
TI  - PMP22 expression in CMT1a neuropathy.

PMID- 7818249
TI  - The influence of apolipoprotein E isotypes on Alzheimer's disease pathology in 40
      cases of Down's syndrome.

PMID- 7818250
TI  - Antagonist activity in cerebellar hypermetria.

PMID- 7818251
TI  - A clue to the pathogenesis of dopa-responsive dystonia.

PMID- 7818252
TI  - Late-onset mitochondrial myopathy.
AB  - In the majority of patients with mitochondrial encephalomyopathies, signs and
      symptoms appear in the first three decades of life. Here we report on a group of
      9 older patients (> 69 years old) with late-onset skeletal myopathy characterized
      by focal accumulations of deleted mitochondrial DNAs (mtDNAs) and altered muscle
      energy status, suggestive of a primary mitochondrial disease. The clinical
      phenotype was somewhat variable. However, all patients shared a common feature of
      insidious moderate proximal muscle weakness; some also showed fatigability and
      axial muscle weakness. In situ hybridization analysis demonstrated accumulations
      of messenger RNAs transcribed from deleted mtDNAs in a relatively large number of
      muscle fibers in the patient group. These fiber segments appeared as ragged red
      with the modified Gomori trichrome stain and hyperreactive with a modified
      succinate dehydrogenase stain. Most were negative for cytochrome c oxidase
      activity. On transverse sections their mean frequency was 0.69% (trichrome) and
      1.97% (succinate dehydrogenase) significantly above control levels. Multiple
      mtDNA deletions were demonstrated by the polymerase chain reaction in both the
      patients and an age-matched control group, but not in younger control subjects.
      Phosphorus 13 magnetic resonance spectroscopy of resting muscle showed a
      decreased phosphocreatine-inorganic phosphate ratio in the patient group. The
      myopathy in this group of patients appears to result from mitochondrial
      dysfunction related to the clonal expansion of different mtDNA deletions in
      individual fiber segments. While the origin of the mtDNA mutations is not clear,
      the phenotype seems to represent an exaggerated form of what is observed in the
      normal aging process.

PMID- 7818253
TI  - Ragged red fibers in normal aging and inflammatory myopathy.
AB  - Ragged red fibers are an important marker for mitochondrial disease. To evaluate
      the hypothesis that mitochondrial dysfunction may play a role in the pathogenesis
      of aging and inclusion body myositis, we studied the frequency of ragged red
      fibers in muscle biopsy specimens from 15 young and 13 old normal adults, and
      from 27 patients with inclusion body myositis, polymyositis, or dermatomyositis.
      Serial transverse cryostat sections were stained with modified Gomori trichrome,
      modified succinic dehydrogenase, and cytochrome c oxidase. The frequency of
      ragged red fibers, determined by measuring the percent number of succinic
      dehydrogenase-positive ragged red fiber equivalents, was significantly higher in
      old compared to young normal subjects (0.33 vs. 0.02%, p < 0.0001). With the
      exception of a single polymyositis biopsy specimen showing a large number of
      ragged red fibers, the frequency of ragged red fibers in patients with
      polymyositis or dermatomyositis was similar to that of age-matched normal control
      subjects. The frequency of ragged red fibers was more than 1% in 7 of 8 patients
      with inclusion body myositis (maximum, 15%). The modified succinic dehydrogenase
      stain was more sensitive than the modified Gomori trichrome in detecting
      accumulation of mitochondria in muscle fibers. Cytochrome c oxidase activity was
      deficient in most ragged red fibers. We conclude that the number of ragged red
      fibers increases with normal aging and may reflect an age-related decline in
      muscle mitochondrial oxidative metabolism. The frequent occurrence of ragged red
      fibers in inclusion body myositis suggests that mitochondrial function may be
      impaired in this disease.

PMID- 7818254
TI  - Mitochondrial myopathy in the elderly: exaggerated aging in the pathogenesis of
      disease.

PMID- 7818255
TI  - Low-dose (7.5 mg) oral methotrexate reduces the rate of progression in chronic
      progressive multiple sclerosis.
AB  - A randomized, double-blinded, placebo-controlled, clinical trial of low-dose,
      weekly, oral methotrexate was performed in 60 patients with clinically definite
      chronic progressive multiple sclerosis (MS) attending a referral-based outpatient
      MS clinic. Study patients were 21 to 60 years old with a disease duration of
      longer than 1 year. Patients' Expanded Disability Status Scale scores were 3.0 to
      6.5 (ambulatory with moderate disability). Patients were first stratified by
      Expanded Disability Status Scale scores, 3.0 to 5.5 and 6.0 to 6.5, and then were
      randomized to receive methotrexate or placebo treatment. Treatment consisted of
      weekly, oral, low-dose (7.5 mg) methotrexate or identical placebo for 2 years,
      followed by observation for as long as 1 year. A composite outcome measurement
      instrument was used and consisted of (1) Expanded Disability Status Scale, (2)
      ambulation index, (3) Box and Block Test, and (4) 9-Hole Peg Test. Failure of
      therapy was indicated by a designated change that was sustained for more than 2
      months in one or more components of this composite measure. Significantly less
      progression of impairment as measured by validated tests of upper-extremity
      function was observed in the methotrexate treatment group in the absence of
      clinically significant toxicity. We conclude that low-dose, weekly, oral
      methotrexate offers a new, relatively nontoxic treatment option for patients with
      chronic progressive MS.

PMID- 7818256
TI  - Myopathy and paraproteinemia with serum IgM binding to a high-molecular-weight
      muscle fiber surface protein.
AB  - We evaluated a 69-year-old man with Waldenstrom's macroglobulinemia (IgM-kappa M
      protein) and progressive weakness over 2 to 3 years. The neurological examination
      showed symmetrical, predominantly proximal weakness. Electrophysiological testing
      revealed small brief motor unit potentials with fibrillations and positive sharp
      waves consistent with an irritative myopathy. The muscle biopsy specimen showed
      myopathic changes including variation in fiber size and increased connective
      tissue but no inflammation. IgM-kappa but not IgM-lambda was deposited along the
      surface of muscle fiber membranes. Serum IgM-kappa but not IgM-lambda from the
      patient stained the surface of normal human muscle fibers but not other regions
      of muscle fibers or other tissues. The serum IgM-kappa at dilutions up to
      1:512,000 bound to a high-molecular-weight muscle protein by Western and dot blot
      studies. By enzyme-linked immunosorbent assay and Western blot analysis, serum
      IgM-kappa bound specifically to the muscle protein and not to other muscle or
      neural antigens, including GM1 ganglioside, myelin-associated glycoprotein, and
      sulfatide. We conclude that the myopathy in our patient is probably related to
      the presence of serum IgM-kappa antibodies directed against a muscle surface
      antigen. Characterization of the target antigen, a high-molecular-weight protein
      located specifically in muscle, should further elucidate the pathogenesis of this
      presumably humorally mediated immune myopathy.

PMID- 7818258
TI  - Clinical outcomes and documentation of partial beneficial effects of
      immunotherapy for multiple sclerosis.

PMID- 7818257
TI  - Histometric effects of ciliary neurotrophic factor in wobbler mouse motor neuron
      disease.
AB  - We investigated the histological effects of ciliary neurotrophic factor on
      degenerating motor neurons, their axons, and skeletal muscles in 68 wobbler mice
      with motor neuron disease. Treatment consisted of recombinant rat or human
      ciliary neurotrophic factor (or a vehicle solution), 1-mg/kg subcutaneous
      injection, three times per week for 4 weeks after the clinical diagnosis. The
      number of motor neurons immunoreactive for calcitonin gene-related peptide was
      higher in mice receiving rat ciliary neurotrophic factor (p < 0.03), although the
      number of choline acetyltransferase-reactive neurons was the same in both treated
      and untreated control groups. Treatment did not prevent vacuolar degeneration of
      motor neurons. In mice treated with human ciliary neurotrophic factor, the
      percentage of axons undergoing acute axonal degeneration (myelin ovoids) was
      smaller in the entire C5 ventral root (p < 0.02) and in the musculocutaneous
      nerve (p < 0.04), and the number of myelinated nerve fibers was 30% higher in
      both nerves (p < 0.01 and p < 0.04, respectively) than in controls. In ciliary
      neurotrophic factor-treated mice, the biceps muscle weight was 20% greater, the
      mean muscle fiber diameter was 30% larger, and the number of atrophied muscle
      fibers was 75% lower than that in the vehicle-treated wobbler mice (p < 0.001 for
      all three results). The number of terminal axonal branching points and the mean
      length of motor end-plates were also higher in the ciliary neurotrophic factor
      treated mice (p < 0.001 and p < 0.02, respectively).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7818259
TI  - Elevated mast cell tryptase in cerebrospinal fluid of multiple sclerosis
      patients.
AB  - Multiple sclerosis (MS) lesions are associated with infiltration of T lymphocytes
      and macrophages that appear to mediate myelin destruction and gliosis (scarring).
      Mast cells are located perivascularly in the brain, are juxtaposed to neurons,
      and have been shown to secrete vasoactive and inflammatory mediators in response
      to neuropeptides and direct nerve stimulation. Mast cells have been previously
      identified in MS lesions, are activated by myelin basic protein, and can
      participate in the regulation of blood-brain barrier permeability, as well as in
      myelin destruction. Here, cerebrospinal fluid from MS patients and controls with
      other neurologic diseases was assayed for histamine, its major metabolite
      methylhistamine, and the specific mast cell marker tryptase. Histamine and
      methylhistamine were not elevated in MS. However, the mast cell specific
      proteolytic enzyme tryptase was significantly elevated in MS, suggesting that
      mast cell activation may be involved in the pathophysiology of this disease.

PMID- 7818260
TI  - The trends in incidence of primary brain tumors in the population of Rochester,
      Minnesota.
AB  - A number of reports have suggested an increasing incidence of primary brain
      tumors, especially malignant astrocytomas, in the elderly population. To
      investigate this issue, we analyzed the incidence and temporal trends of primary
      intracranial neoplasms diagnosed in the population of Rochester, Minnesota, over
      the 40 years between 1950 and 1990. The incidence of symptomatic primary brain
      tumors (excluding patients diagnosed incidentally at autopsy and by neuroimaging
      studies) increased from 9.5 per 100,000 population per year in 1950 to 1969 to
      12.5 per 100,000 per year in 1970 to 1989; this change was not statistically
      significant (chi 2 trend, 1.89; p = 0.17). While the incidence of pituitary
      adenomas increased significantly between the two periods (chi 2 trend, 4.44; p =
      0.04), the incidence trends of all gliomas, malignant astrocytomas, and
      meningiomas showed no change among persons younger than 65 years as well as those
      65 years and older. The number of patients incidentally found to have neoplasms
      by neuroimaging studies increased in the recent 20-year period (chi 2 trend,
      4.08; p = 0.04). The average age- and sex-adjusted incidence rates per 100,000
      per year during the study period in the population of Rochester, Minnesota, for
      symptomatic tumors were 5.0 for all gliomas, 3.3 for malignant astrocytomas, 2.0
      for meningiomas, and 2.4 for pituitary adenomas. In conclusion, our data indicate
      that the reported increase in the incidence of primary brain tumors is an
      artifact of improvement in diagnostic technology and practice.

PMID- 7818261
TI  - Regional cerebral blood flow changes in motor cortical areas after transient
      anesthesia of the forearm.
AB  - To study the effect of deafferentation on cortical areas activated by movement of
      the proximal muscles, we measured regional cerebral blood flow with positron
      emission tomography and 15O-labeled water. Flexion-extension movements of the
      right elbow before deafferentation were associated with an increase of regional
      cerebral blood flow in the primary sensorimotor area bilaterally, posterior
      supplementary motor area bilaterally, ipsilateral cerebellum, contralateral
      putamen, premotor area, anterior cingulate area, and posterior parietal region.
      Transient anesthesia of the right forearm induced by ischemic block caused an
      increase of regional cerebral blood flow in the primary sensorimotor area
      bilaterally at rest, but there was no change of regional cerebral blood flow with
      movement, indicating that the movement-related change in cerebral blood flow was
      reduced. These findings are consistent with increased excitability of neurons as
      a result of deafferentation. In the supplementary motor area, anesthesia did not
      induce any change in regional cerebral blood flow at rest, but there was a
      decline with movement, again indicating a reduction of the change in cerebral
      blood flow related to movement. This might be due to a reduction in sensory
      feedback because of the anesthesia.

PMID- 7818262
TI  - Tumor necrosis factor-alpha messenger RNA expression in patients with relapsing
      remitting multiple sclerosis is associated with disease activity.
AB  - We determined the cytokine messenger RNA (mRNA) expression pattern of blood
      mononuclear cells in 29 patients with relapsing-remitting multiple sclerosis
      every 4 weeks over a period of 12 months. During this period 27 relapses occurred
      in 14 patients (48%). Progression of disease activity as assessed by the
      occurrence of new lesions on nonenhancing T2-weighted magnetic resonance images
      of the head was detected in 12 (48%) of 25 patients. Using a semiquantitative
      polymerase chain reaction we demonstrated significant increases in tumor necrosis
      factor-alpha mRNA expression in peripheral blood mononuclear cells prior to a
      relapse. In 24 (85%) of 27 relapses increased tumor necrosis factor-alpha mRNA
      expression preceded clinical symptoms by 4 weeks. A similar pattern was observed
      for lymphotoxin mRNA expression. At the same time, transforming growth factor
      beta and interleukin-10 mRNA levels declined. Fluctuations in the mRNA expression
      of tumor necrosis factor-alpha were also observed in 6 patients with stable
      disease who had active magnetic resonance scans on follow-up. No correlation of
      disease activity was observed with interleukin-1 beta, -4, or -6, inferferon
      gamma or endothelin-1 mRNA expression. From these data it can be concluded that
      variations in cytokine mRNA expression in blood mononuclear cells are correlated
      with disease activity in relapsing-remitting multiple sclerosis. It may be a
      valuable parameter to monitor the immunological status of patients in future
      clinical trials.

PMID- 7818263
TI  - Experimental ischemic neuropathy: salvage with hyperbaric oxygenation.
AB  - Hyperbaric oxygenation is effective in augmenting the delivery of oxygen to
      tissue, but also causes oxidative stress. As part of our focus on improving
      peripheral nerve salvage from ischemic fiber degeneration, we evaluated whether
      hyperbaric oxygenation rescues peripheral nerve, rendered ischemic by
      microembolization, from ischemic fiber degeneration. The supplying arteries of
      rat sciatic nerve were embolized with microspheres of 14 microns diameter at
      moderate (2 x 10(6)) and high (5.6 x 10(6)) doses. Rats were randomized to
      receive hyperbaric oxygenation treatment (2.5 atm 100% oxygen for 2 hours/day for
      7 days beginning within 30 minutes of ischemia), or room air. End points for the
      embolized limb were (1) behavioral scores (0-11 in increasing levels of limb
      function), (2) nerve action potential of sciatic-tibial nerve, (3) nerve blood
      flow, and (4) histological grade as percentage of fibers undergoing ischemic
      fiber degeneration (0 = < 5%; 1 = 5-25%; 2 = 26-50%; 3 = 51-75%; 4 = > 76%).
      Nerve blood flow and nerve action potential were uniformly absent and more than
      90% of fibers had degenerated in both control and treatment groups receiving high
      doses. Control and treatment groups receiving moderate doses were well matched by
      level of ischemia (8.5 +/- 0.3 [N = 18] vs 7.7 +/- 0.4 ml/100 gm/min [N = 18], p
      > 0.05) but were significantly different by behavior score (5.6 +/- 0.7 vs 9.2 +/
      0.5 [N = 19], p < 0.001), nerve action potential (1.4 +/- 1.0 vs 3.9 +/- 0.5 [N
      = 6], p < 0.05), and histology (2.4 +/- 0.4 [N = 5] vs 0.8 +/- 0.5 [N = 4], p <
      0.05). On single teased fiber evaluation, the predominant abnormality was E
      (axonal degeneration). We conclude that hyperbaric oxygenation will effectively
      rescue fibers from ischemic fiber degeneration, providing the ischemia is not
      extreme.

PMID- 7818264
TI  - Comparative study of selegiline plus L-dopa-carbidopa versus L-dopa-carbidopa
      alone in the treatment of Parkinson's disease.
AB  - The long-term effect of selegiline (L-deprenyl) in the treatment of Parkinson's
      disease has not been clearly delineated. We report on a group of patients whose
      treatment was initiated with selegiline (n = 43) and then subsequently included L
      dopa-carbidopa (Sinemet) and in whom an extended period of observation was
      carried out; they are compared to a group of patients whose treatment consisted
      of L-dopa-carbidopa alone (n = 39). In each, serial observations of the
      parkinsonian state and the response to treatment on a yearly basis for a period
      of 5 years were performed. No significant difference in the Hoehn-Yahr stage or
      in the motor subscores of tremor, rigidity, bradykinesia, and gait-posture was
      found between the two groups, nor was there a significant difference in the
      incidence of fluctuating responses or dyskinesias. The group that received
      combination therapy required less L-dopa than did the group that received L-dopa
      carbidopa alone during the first 3 years of treatment and a similar trend was
      evident in years 4 to 5. We conclude that minimal benefits accrued to the
      parkinsonian patients from long-term use of selegiline. No clinical evidence to
      support the claim of "neuroprotective" properties was found. Selegiline's major
      usefulness is to modify the fluctuating therapeutic response seen with L-dopa
      carbidopa.

PMID- 7818265
TI  - Genetic identity of Fukuyama-type congenital muscular dystrophy and Walker
      Warburg syndrome.
AB  - Both Fukuyama-type congenital muscular dystrophy (FCMD) and Walker-Warburg
      syndrome (WWS) are unusual genetic syndromes consisting of congenital muscular
      dystrophy and complex malformations of the brain and eye. It has been intensively
      discussed whether FCMD and WWS belong to the same disease entity or not. We
      analyzed a family in which 3 siblings were affected with either FCMD or WWS by
      using polymorphic microsatellites flanking the FCMD locus on chromosome 9q31-33.
      The results suggested that both FCMD and WWS siblings shared the identical
      combination of mutations on either allele of the FCMD locus. FCMD and WWS could
      be "genetically" identical.

PMID- 7818266
TI  - Safe disposal of diisopropyl fluorophosphate (DFP).
AB  - Diisopropyl fluorophosphate (DFP), a volatile highly toxic enzyme inhibitor, in
      buffer (pH 3, pH 5, pH 7, pH 9, pH 11, Hank's, Dulbecco's, PBS, TBE, and HEPES)
      or water (10 mM), in DMF solution (200 mM), and bulk quantities can be degraded
      by adding 1M NaOH. The DFP was completely degraded, as determined by enzymatic
      assay, and the final reaction mixtures were not mutagenic.

PMID- 7818268
TI  - On the shoulders of giants...

PMID- 7818267
TI  - Effect of sodium dodecyl sulfate on lipase of Candida lipolytica.
AB  - The effects of sodium dodecyl sulfate on extracellular lipase produced by Candida
      lipolytica have been studied. The microorganism was grown in culture medium
      containing different sodium dodecyl sulfate concentrations added to the culture
      at different intervals of growth. The extracellular lipase activity was not
      detected when the treated culture supernatants were directly tested in Yeast Mold
      Agar-Triolein-Rhodamine plates, regardless of surfactant addition time and
      concentrations. However, after ammonium sulfate precipitation and dialysis, the
      extracellular lipase activity could be recovered. Therefore, the surfactant,
      under the experimental conditions used here, does not seem to be able to inhibit
      lipase production, but it does inhibit the enzyme activity because of its
      presence in the mixture of the reaction.

PMID- 7818269
TI  - A comparison of tympanic thermometer readings to pulmonary artery catheter core
      temperature recordings.
AB  - The purpose of this study was to determine the accuracy of FirstTemp (Intelligent
      Medical Systems, Carlsbad, CA) tympanic thermometer readings compared with core
      body temperatures obtained via pulmonary artery catheter (PAC). Five measurements
      were obtained on 19 cardiovascular surgery patients. Tympanic thermometer
      measurements tended to be higher than PAC measurements. However, most of the
      differences were not clinically significant. Differences found between right and
      left ear measurements were most likely due to poor measurement technique. When
      the correct technique is used, nurses can be confident that tympanic temperature
      readings are clinically accurate.

PMID- 7818270
TI  - Development of discharge information for recovery after coronary artery bypass
      surgery.
AB  - Descriptions of coronary artery bypass graft (CABG) recovery experiences were
      elicited for development of a preparatory discharge information intervention. A
      convenience sample of 15 men and 5 women were interviewed about the concerns,
      emotions, and physical sensations they experienced after CABG and the actions
      they found most useful to manage the recovery at three time points: (a)
      discharge; (b) 2 days after discharge; and (c) 3 weeks after discharge. Concerns
      of subjects centered on pain management and return to independence in activities
      of daily living. Reports of negative emotions increased over the first month of
      recovery and included depression, anger, and anxiety. Subjects most frequently
      reported physical sensations associated with fatigue, chest incision, sleeping,
      leg incision, shoulder and neck muscles, and coughing. Descriptions of the CABG
      recovery experience provided data for development of discharge information, that
      focused on concrete experiences from the viewpoint of the person having CABG
      surgery and included orienting information about the onset, sequence, and
      duration of the experiences.

PMID- 7818271
TI  - Use of a nursing intensity system as a measure of patient function.
AB  - The purpose of this study was to determine whether a nursing intensity system
      could be used as a valid and reliable measure of patient function (ability to
      perform activities of daily living). Eighty seven patients on the medical service
      were randomly selected for inclusion in the study. Functional status assessment
      was obtained by the Katz Index and compared with functional status data obtained
      from the nursing intensity system. Correlation between the two measures was high
      (r = .71, p < .001). The nursing intensity system was also found to have high
      internal consistency (alpha = .85). It was concluded that such systems have the
      potential to provide useful measures of function.

PMID- 7818272
TI  - Use of a pressure gauge to differentiate gastric from pulmonary placement of
      nasoenteral feeding tubes.
AB  - This study was conducted to determine the reliability and validity of using a
      pressure gauge to differentiate gastric from pulmonary placement of nasoenteral
      tubes in nonmechanically ventilated patients. It was anticipated that on
      inhalation, tubes properly placed in the gastric region would yield positive
      readings owing to positive gastric pressures. Conversely, tubes that were
      inadvertently placed in the pulmonary system should yield negative pressure
      readings owing to the negative pulmonary pressures that exist on inhalation.
      Forty-six subjects were enrolled in the study. Of those, 44 had positive gauge
      readings, and x-ray results showed that these nasoenteral tubes were in the
      gastric region. Two patients had negative gauge readings, and the x-rays for both
      of these subjects demonstrated that the nasoenteral tubes were in the pulmonary
      system. Thus, the findings were consistent with what was anticipated. Despite the
      small sample size, the results of this study indicate that this method of
      assessing nasoenteral tube placement may be a safe, reliable, and cost-effective
      method of differentiating gastric from pulmonary tube placement in this patient
      population.

PMID- 7818273
TI  - Elders' and family members' perspectives in planning for hospital discharge.

PMID- 7818274
TI  - A discharge planning questionnaire for clinical practice.

PMID- 7818275
TI  - A review of approaches to integrating research and practice.

PMID- 7818276
TI  - Complement profiles in human skin lymph during the course of irritant contact
      dermatitis.
AB  - Using microsurgery a superficial peripheral lymph vessel draining the skin of the
      upper and medial part of the foot was cannulated on the lower leg of two healthy
      human volunteers. An irritant contact dermatitis was induced 2 days later by the
      application of 10% sodium lauryl sulphate to the drained skin area. After a
      further 3 days the spontaneously regressing skin reaction was treated with
      clobetasol propionate. Lymph was continuously collected in two aliquots per day
      for 7 days. The levels of total protein, of albumin and globulins, and of
      complement components of the classical, the alternative and the lytic pathway as
      well as the C4A and C4B gene products and the regulatory proteins FB, C1INH,
      C4BP, FH and FI were determined by ELISA and radial immunodiffusion techniques.
      Postoperatively, the levels of complement proteins and globulins in the lymph
      were 5-10 times lower than those in normal human serum, but increased during the
      course of the skin reaction, while the irritant contact dermatitis did not induce
      a change in their plasma concentration. In comparison to the baseline, the mean
      values for C1q, C1r, C2, C5, C6, C7, C8, C9, FB, C1INH, C4BP, FH and FI exhibited
      a 3-5-fold increase, C3, total C4, albumin and the alpha 1-globulin fraction a 6
      9-fold increase, and C1s, C4A, C4B, FB and alpha 2-, beta- and gamma-globulins a
      10-20-fold increase.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7818277
TI  - Detection of Epstein-Barr virus genome in primary cutaneous T and B cell
      lymphomas and pseudolymphomas.
AB  - The Epstein-Barr virus (EBV) genome has recently been identified in Hodgkin's
      disease (HD) and nodal non-Hodgkin's lymphomas (NHL). In order to elucidate the
      possible aetiopathogenetic role of EBV in benign and malignant
      lymphoproliferative disorders we investigated skin specimens from 24 patients
      with a primary cutaneous lymphoproliferative disorders (10 T-cell lymphomas 6 B
      cell lymphomas and 8 pseudolymphomas) and from 22 normal individuals for the
      presence of EBV DNA using the polymerase chain reaction (PCR) technique and in
      situ hybridization (ISH) on formalin-fixed paraffin-embedded tissue sections. EBV
      DNA was identified by PCR in one of two cases of mycosis fungoides, in one of
      seven cases of pleomorphic T-cell lymphomas, in one case of centroblastic (CB)
      lymphoma of six B-cell lymphomas, and in three of eight pseudolymphomas. The EBV
      genome was also found in 2 of 22 specimens of normal skin. The small EBV-encoded
      nuclear RNAs, EBERs, were not detected in any PCR-positive sample by ISH. Based
      on our PCR and ISH findings, EBV does not seem to play a significant role in the
      development of cutaneous lymphomas.

PMID- 7818278
TI  - Evidence for a role of corneodesmosin, a protein which may serve to modify
      desmosomes during cornification, in stratum corneum cell cohesion and
      desquamation.
AB  - Corneodesmosin, defined as the protein recognized by the monoclonal antibody G36
      19, is a recently described late differentiation protein of human cornified
      epithelium. In the stratum corneum it is localized in the extracellular parts of
      modified desmosomes (corneodesmosomes) and adjacent parts of the cornified cell
      envelope. The aim of the present study was to investigate whether corneodesmosin
      undergoes changes in the stratum corneum which can be related to the cohesive
      state of the tissue and to desquamation. Extracts of plantar stratum corneum from
      various tissue levels and tape-stripped non-palmoplantar stratum corneum were
      analysed by immunoblotting with G36-19. In addition, the fate of corneodesmosin
      during shedding of surface cells in a recently described in vitro model of
      desquamation in plantar stratum corneum was investigated and compared with the
      degradation of the desmosomal protein desmoglein I in this system. The apparent
      molecular weights of the major G36-19-positive components in plantar stratum
      corneum ranged between 33 and 48 kDa. The components with the highest molecular
      weights were predominant in the deepest tissue layers. In the intermediate tissue
      layers G36-19-positive components of molecular weight 33-36, 39 and 44-48 kDa
      were found. There seemed to be a further degradation of the 33 to 36-kDa
      components in the most superficial parts of the tissue. In surface cells
      dissociated in vivo as well as in vitro no G36-19-positive components with
      molecular weights above 36 kDa were detected. Results from analyses of
      nonpalmoplantar stratum corneum suggested that corneodesmosin is degraded in this
      tissue in a way that may be similar to that in plantar stratum corneum.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7818279
TI  - Platelet activating factor (PAF) and lyso-PAF in psoriasis.
AB  - Previous studies have shown that scale from lesional psoriatic skin contains
      substantial amounts of platelet activating factor (PAF). In this study, PAF and
      its immediate precursor, lyso-PAF, were measured in exudates from abrasions on
      lesional and uninvolved psoriatic skin, and from skin of healthy subjects. The
      mean amounts of PAF recovered from lesional and uninvolved psoriatic skin (n =
      13) and from healthy skin (n = 14) were not significantly different (range 0.05
      2.14 pmol/sample). Mean recoveries of lyso-PAF from lesional psoriatic skin (n =
      9) and skin of healthy subjects (n = 13) were also similar (9.5 +/- 1.9 and 11.0
      +/- 1.9 pmol/sample, respectively), but significantly less lyso-PAF was found in
      exudates from the uninvolved psoriatic skin (n = 9; 3.1 +/- 0.4 pmol/sample; P <
      0.01 relative to both lesional psoriasis and healthy skin). The finding of
      reduced lyso-PAF in uninvolved psoriatic skin was unexpected because increased
      phospholipase-A2 activity is associated with psoriasis. These results do not
      support the hypothesis that extracellular PAF contributes significantly to the
      inflammation associated with psoriasis.

PMID- 7818280
TI  - A specific 4977-bp deletion of mitochondrial DNA in human ageing skin.
AB  - Mitochondrial DNA (mtDNA) mutations have recently been proposed as important
      contributors to ageing and degenerative diseases. In this study, we applied the
      polymerase chain reaction technique to detect 4.977 bp-deleted mtDNA, the most
      common and abundant deletion of mtDNA, in normal human skin. None of the skin
      specimens from patients less than 60 years of age were found to bear this type of
      mtDNA deletion. The incidence of the 4977-bp-deleted mtDNA increased with
      advancing age. The incidence of the deletion was 20%, 46.7% and 83.4% for
      patients of the age groups of 61-70, 71-80, and 81-90 years, respectively.
      Moreover, the incidence of 4977-bp-deleted mtDNA was significantly higher in
      exposed skin than that in non-exposed skin. We suggest that mtDNA mutations are
      molecular events associated with the human skin ageing process.

PMID- 7818281
TI  - Analysis of the age-related composition of human skin collagen and collagens
      synthesized by fibroblast culture.
AB  - Age-related differences in the composition and the post-translational
      modifications of human skin collagens were examined in the present study. The
      data were compared with results of collagen synthesis from in vivo-aged
      fibroblasts in culture. Skin extracts and newly synthesized collagen from
      fibroblast cultures derived from both old and young donor groups showed the same
      ratio of collagen III to collagen I. Furthermore, no difference was noted in the
      degree of prolyl and lysyl hydroxylation of collagen I and collagen III Young and
      old fibroblasts synthesized a similar quantity of collagen in vitro. The data
      suggest that fibroblasts maintain a uniform level of collagen production,
      composition and modification independent of the age of the donor.

PMID- 7818282
TI  - Expression of laminin, type IV procollagen and 230 kDa bullous pemphigoid antigen
      genes by keratinocytes and fibroblasts in culture: application of the polymerase
      chain reaction for detection of small amounts of messenger RNA.
AB  - In order to clarify whether keratinocytes and/or fibroblasts express genes
      encoding basement membrane zone macromolecules, we examined laminin, type IV
      collagen and 230 kDa bullous pemphigoid antigen (BPAG1) gene expression in
      keratinocytes and fibroblasts in culture. Northern transfer analysis revealed the
      presence of specific mRNA transcripts for alpha 1(IV) and alpha 2(IV) chains of
      type IV collagen as well as B1 and B2 chains of laminin in both fibroblast and
      keratinocyte RNA. Laminin A mRNA, however, was detected in fibroblasts but not in
      keratinocytes. In contrast, BPAG1 mRNA was detected in keratinocytes but not in
      fibroblasts using the same RNA preparations. A polymerase chain reaction (PCR)
      using laminin A and BPAG1-specific primers produced amplified DNAs with the
      predicted sizes in reverse-transcripted cDNA derived from keratinocyte and
      fibroblast RNA, respectively. These results provide evidence that normal human
      skin keratinocytes and fibroblasts express genes encoding laminin A, B1, B2,
      alpha 1(IV), and BPAG1 at a steady-state level. Moreover, the PCR for detecting
      small amounts of mRNA suggested that both keratinocytes and fibroblasts can be
      utilized for the analysis of DNA mutations in inherited skin diseases affecting
      the basement membrane zone, such as epidermolysis bullosa.

PMID- 7818283
TI  - Point mutations and allelic loss in the TP53 locus of cutaneous malignant
      melanomas.

PMID- 7818284
TI  - sICAM-1, sIL-2R and beta 2-microglobulin serum levels in patients affected with
      psoriasis: relationship with disease severity.

PMID- 7818286
TI  - Assessment of urban population exposure to trichloroethylene and
      tetrachloroethylene by means of biological monitoring.
AB  - Exposure of the general population to trichloroethylene and tetrachloroethylene
      under normal environmental conditions, achieved with biological monitoring, was
      assessed, and the possible influence of these compounds via drinking water on the
      body burden was revealed. A total of 79 subjects with no known solvent exposure
      was selected, by stratified sampling, from the residents of the city of Zagreb.
      Trichloroethylene and tetrachloroethylene were determined in blood, and
      trichloroethanol and trichloroacetic acid were determined in plasma and urine.
      Drinking water samples were also analyzed for trichloroethylene and
      tetrachloroethylene. Concentrations of trichloroethylene and tetrachloroethylene
      in blood, trichloroacetic acid in plasma, trichloroacetic acid in urine,
      trichloroethylene in drinking water, and tetrachloroethylene in drinking water
      were as follows: < 0.015 to 0.090 micrograms/l, < 0.010 to 0.239 micrograms/l,
      8.6 to 148.1 micrograms/l, 1.67 to 102.3 micrograms/24 h, < 0.05 to 22.93
      micrograms/l, and 0.21 to 7.80 micrograms/l, respectively. The variation in all
      results presented is probably a reflection of different environmental
      contamination with trichloroethylene and tetrachloroethylene in the different
      city areas. Correlation analyses revealed significant relationships between
      trichloroethylene and tetrachloroethylene in blood (r = .402, p = .0004);
      trichloroacetic acid in urine and in plasma (r = .522, p = .0000); and
      trichloroethylene and tetrachloroethylene in drinking water (r = .800, p =
      .0000). A division of all parameters into a subgroup (n = 58), taking drinking
      water concentrations of trichloroethylene above 3 micrograms/l as a basis,
      demonstrated the same significant relationships as mentioned above.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7818285
TI  - Irritative and systemic symptoms following exposure to Microban disinfectant
      through a school ventilation system.
AB  - Microban, a pesticide not registered in California, was sprayed into an operating
      heating/ventilation/air conditioning (HVAC) unit at an elementary school in San
      Francisco, California. This incident occurred on Monday, September 28, 1992,
      while 396 students and 67 staff members were in the school. The Microban
      formulation used contains ortho-phenylphenol (0.21%), a quaternary ammonium
      complex (di-isobutylphenoxy-ethoxy-ethyldimethylbenzyl-ammonium chloride, 0.69%),
      and bromine (0.04%). This study of the health effects of Microban mist exposure
      on the school staff was conducted as a result of legal and toxicological
      concerns. California registration for this formulation had been denied because of
      inadequate data and because there were concerns about inhalation toxicity in test
      animals. Predicted health effects from short-duration exposure to Microban are
      primarily skin and mucous membrane irritation. A self-administered health symptom
      questionnaire that covered the work week following the evacuation was used to
      determine a pattern of higher symptom risks for those who were at work on Monday
      and who reported that they felt they were exposed to a chemical. Symptoms, which
      were generally consistent with exposure to an irritating chemical, were elevated
      on Monday and Tuesday; the symptoms normalized by the end of the work week. No
      additional health effects were detected following application of chlorpyrifos to
      cracks and crevices for ant control 2 d following the Microban incident. Strict
      supervision and coordination of pesticide use in public schools are recommended
      to prevent adverse health effects and emotional trauma in students and staff.

PMID- 7818287
TI  - Determinants of polychlorinated biphenyls (PCBs) in the sera of mothers and
      children from Michigan farms with PCB-contaminated silos.
AB  - Blood samples were collected from 28 mothers and from 38 school-aged children
      from Michigan farms on which there were polychlorinated biphenyl (PCB)
      contaminated silos. The samples were analyzed for PCBs and other contaminants,
      including polybrominated biphenyls (PBBs) and dichlorodiphenyl trichloroethane
      (p,p'-DDT + p,p'-DDE) via packed column gas chromatography. The PCBs were
      quantified, using the Webb-McCall method, with Aroclors 1016 and 1260 used as
      reference standards. Approximately 42% of the children had serum PCB levels above
      the detection limit of 3.0 ng/ml. The values ranged from 3.1 to 23.3 ng/ml, with
      a mean of 6.8 ng/ml. In contrast, PCBs were detected in 86% of the mothers. The
      mean serum concentration was somewhat higher for the mothers (9.6 ng/ml), but the
      range was similar to that found for the children. PBBs were not detected in any
      of the children, but were present in trace amounts in 25% of the mothers.
      Conversely, DDT was present in 66% of the children and 93% of the mothers. As
      with PCBs, DDT concentrations were somewhat higher in the mothers. DDE accounted
      for 89% of the total DDT in serum. Various potential sources of exposure were
      evaluated as possible determinants of serum PCB levels, using hierarchical
      multiple regression. Years of residence on a silo farm and consumption of PCB
      contaminated Great Lakes fish both accounted for significant portions of the
      variance in maternal serum PCB levels. Exposure via breast-feeding explained a
      large and highly significant proportion of the variance in the children's serum
      PCB concentrations, suggesting that breast milk was the primary source of PCB
      exposure for these children.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7818288
TI  - Silica exposure and chronic airflow limitation in pottery workers.
AB  - We assessed the relationship between exposure to silica dust and chronic airflow
      limitation in an epidemiological survey conducted among pottery workers and
      controls who were of the same socioeconomic status (average age: 35 y; 78%
      males). Data were collected by questionnaire for respiratory symptoms, allergy,
      respiratory history, smoking habits, and occupation. Lung function was measured
      with a computer-equipped Gauthier spirometer. We excluded subjects with silicosis
      or doubtful chest x-ray, and two exposure levels were defined. No differences
      were observed between exposed subjects and controls with respect to respiratory
      conditions. Mean pulmonary function values for men and women were significantly
      lower, after adjustment for age, height, and smoking habits, in even indirectly
      exposed pottery workers, compared with controls. These results suggest that
      exposure to silica dust is a risk factor for chronic airflow limitation and is
      independent of radiographic changes.

PMID- 7818289
TI  - Respiratory consequences of exposure to wood dust and formaldehyde of workers
      manufacturing oriented strand board.
AB  - A cross-sectional study was performed at a plant in which 99 workers were
      employed in the manufacture of oriented strand board. This group was compared
      with 165 unexposed workers from the petroleum industry. Both groups were
      assessed, using a questionnaire, spirometry, and skin prick tests to common
      environmental antigens. Environmental studies showed a low dust level of 0.27
      mg/m3, consisting of particles of a mass median aerodynamic equivalent diameter
      of 2.5 microns. There were variable concentrations of formaldehyde, up to 0.27
      ppm. A significant difference between the oriented strand board workers and oil
      field workers was noted for the forced expiratory volume in 1 s/forced vital
      capacity ratio, without significant differences in either the forced expiratory
      volume in 1 s or the forced vital capacity. Oriented strand board workers who
      were current smokers were three times as likely to have a forced expiratory
      volume in 1 s/forced vital capacity ratio of less than 75% of that found in the
      currently smoking oil field workers. Significant reductions in forced expiratory
      volume in 1 s (p = .044) and forced vital capacity (p = .022) in oriented strand
      board workers were noted across the work shift. The oriented strand board workers
      complained of self-reported asthma and of lower respiratory tract symptoms
      significantly more frequently than did oil workers for all of the symptoms
      examined. The prevalence of atopy was not different in the two groups. Lung
      function was significantly better in oriented strand board workers who had no
      symptoms, compared with oriented strand board workers who were
      symptomatic.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7818290
TI  - Distribution of blood lead levels in 1,047 Saudi Arabian children with respect to
      province, sex, and age.
AB  - Relationships between blood lead concentrations in 1,047 children aged 2 mo to 16
      y and age, sex, and province (i.e., residence) were examined. The relationships
      were consistent with other studies, in which mean blood lead concentrations
      reportedly increased during the first 5 y of life, after which began to decrease,
      reaching a minimum at approximately 16 y of age. However, boys who were more than
      6 y of age had higher blood lead concentrations than similarly aged girls. Blood
      lead levels of children living in the Eastern Province were higher than levels
      found in children from other provinces. Most of the children in this study who
      had elevated blood lead concentrations resided in small towns, e.g., Ehssa,
      Abqiq, Hofouf, rather than in cities such as Dammam and Dahran. Factors, such as
      socioeconomic status and cultural habits (e.g., diet, use of traditional remedies
      and cosmetics), may have contributed to this result.

PMID- 7818291
TI  - Polychlorinated biphenyls, 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (p,p'
      DDT) and 1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene (p,p'-DDE) in human plasma
      related to fish consumption.
AB  - Fatty fish species, e.g., salmon and herring, in the Baltic Sea have high levels
      of polychlorinated biphenyls (PCBs) and 1,1,1-trichloro-2,2-bis(p
      chlorophenyl)ethane (p,p'-DDT), and its main metabolite: 1,1-dichloro-2,2-bis(p
      chlorophenyl)-ethylene (p,p'-DDE). We determined levels of 10 different PCB
      congeners, including non- and mono-ortho-PCBs, as well as DDT and DDE, in human
      blood plasma from 37 subjects with varying intake of fish (0-1 750 g/wk) from the
      Baltic Sea. With respect to all of the PCB congeners we investigated, as well as
      for DDT and DDE, there were statistically significant associations with fish
      intake. Thus, fish from the Baltic Sea is a major source of exposure to these
      compounds in Swedes. Polychlorinated dibenzo-p-dioxins (PCDD) and dibenzofurans
      (PCDF) had been determined earlier in 29 of the subjects. The PCB contribution to
      "dioxin-like" effects among high consumers of fish (calculated as Nordic TCDD
      equivalents) was almost 80%, whereas that from PCDD and PCDF was only 20%.

PMID- 7818292
TI  - Occupational and environmental exposure to perchloroethylene (PCE) in dry
      cleaners and their family members.
AB  - Perchloroethylene exposure in 28 dry-cleaning establishments and in 25 homes
      occupied by dry cleaners in Modena, Italy, was investigated. Environmental air
      samples and alveolar air samples from dry cleaners (n = 60) and from their family
      members (n = 23) were collected. The degree of perchloroethylene on the dry
      cleaning premises varied widely from establishment to establishment. Spot
      sampling ranged from 0.6 to 75 mg/m3, whereas sampling by personal passive
      dosimeters ranged from 2.6 to 221.5 mg/m3 (8-h time weighted average values).
      Perchloroethylene in alveolar air samples collected at the end of the work day
      correlated closely with the 8-h time weighted average values (r = .750, p =
      .001), and correlated also with alveolar air samples collected at home in the
      evening (r = .665, p = .001) and the following morning (r = .549, p < .001).
      Perchloroethylene levels inside the homes of dry cleaners appeared significantly
      higher than in 29 houses selected as controls (Mann Whitney U test, p < .001).
      Perchloroethylene in alveolar air samples collected at home suggests that
      nonoccupational exposure to perchloroethylene for family members of dry cleaners
      exists.

PMID- 7818293
TI  - [Our experience with mitomycin C in the prophylaxis of superficial bladder
      tumors; retrospective study].
AB  - From 1984 to 1991, fifty-one patients completed prophylactic endovesical
      treatment with mitomycin C after transurethral resection of a bladder carcinoma
      Ta, Tl. The mean disease-free period was 31.2 months; twenty patients had
      recurrences (39.2%) and five (9.8%) had a progression in tumor stage. No
      statistically significant differences were found relative to the recurrences and
      tumor number, stage and size. The patients with prior tumors had recurrences
      before (p < 0.05) and more times (p < 0.01) than the primary group.

PMID- 7818294
TI  - [Squamous cell carcinoma of the urinary bladder. Clinico-pathologic study of 7
      cases].
AB  - A retrospective review of 552 patients with primary bladder cancer yielded 7
      cases (1.2%) of pure squamous cell carcinoma. Their clinical presentations did
      not differ from conventional transitional cell carcinomas, gross hematuria being
      the most frequent complaint (6 cases). All the cases presented as flat tumors.
      They were large and frequently affected more than one topographic area. The
      trigone was almost always affected (6/7). Three cases were considered low and 4,
      high grade. There were no dysplastic changes on the peripheral mucosa in any
      case. At the time of diagnosis, all of them were deeply invasive (pT3 and pT4).
      Two cases were Stage III and 5 Stage IV, with involvement of lymph nodes and
      metastases to the lung (2 cases), liver (1 case), and bone (1 case). All the
      patients died of tumor and the overall survival was very poor (range 6-37 months;
      mean 17.4).

PMID- 7818295
TI  - [Comparative results of different types of urethropexy in the treatment of stress
      urinary incontinence in women].
AB  - We conducted a clinical and urodynamic study in 70 patients who had undergone
      different urethropexy procedures for stress urinary incontinence. Urethropexy had
      achieved positive results in 87% of the patients. Incontinence persisted in 21%
      of the patients. Urethropexy significantly reduced the urge-incontinence and
      frequency associated with this disorder. Anterior urethropexy did not increase
      the incidence of poor results in the present series since no patient had
      intrinsic urethral involvement. The suprapubic and the combined techniques
      achieved the following cure rates: Marshall-Marchetti-Krantz (92%), Burch (100%),
      Ramirez simplified (80%), Raz (60%). The cure rate for the Kelly vaginal
      technique was found to be lower (57%).

PMID- 7818296
TI  - [Clinico-urodynamic correlation in hormone-dependent events in urinary
      incontinence].
AB  - The present study was conducted to determine the correlation between the hormone
      dependent events and the manifestation or exacerbation of symptoms of urinary
      incontinence in 117 incontinent female patients. This finding was almost
      exclusively observed in patients with sphincter incompetence. Patients who were
      clinically influenced had a higher flow rate and profile changes, whereas
      pregnancy and menstruation correlated with the predominant changes. This
      subjective clinical finding may be useful in predicting a more limited continence
      and may therefore indicate the postoperative prognosis.

PMID- 7818297
TI  - [Endoscopic treatment of congenital paraureteral diverticuli and cavities].
AB  - We report 4 cases of primary congenital paraurethral diverticula or cavities (3
      diverticula and 1 cyst of Cowper's glands) that were treated by endoscopic
      surgery. All the foregoing cases were diagnosed as primary in the absence of
      coexisting pathologies or associated disorders. The wall between the diverticulum
      and the urethral lumen was sectioned endoscopically. All patients recovered
      normal clinical and morphological status.

PMID- 7818298
TI  - [Does hyponatremia predict post-transurethral resection of the prostate
      syndrome?].
AB  - The florid post-TUR syndrome observed in one of our patients prompted us to
      conduct a prospective study on 100 males undergoing TUR to determine the natremia
      levels that could herald the presentation of this syndrome. Several parameters
      were evaluated, including pre- and post-operative serum sodium levels, total
      volume of irrigant used, and the weight of the resected prostate. Although the
      natremia levels dropped significantly in 4 patients, only the patient who had
      motivated this study developed symptoms and evidently no conclusions can be drawn
      on the basis of a single observation.

PMID- 7818300
TI  - [Penile prosthesis. Implantation under local anesthesia].
AB  - We report our motivation, technique, results and the current status of penile
      prosthesis implantation under local anesthesia at our institution. The lack of
      anesthetists to cope with the surgical demands and the conflicting views on the
      priority assigned to the different pathologies prompted us to seek an alternative
      approach. TECHNIQUE: Anesthetic blockade with mepivacaine (2%) for the pudendal
      nerve branches (dorsal and perineal, in some cases; cavernous, in the first one)
      responsible for penile innervation, and anesthetic blockade of the genitofemoral
      and ilioinguinal nerves that innervate the scrotum and its contents. Of the five
      patients, 80% had excellent and 20% had good tolerance of the procedure. The
      definition of the foregoing categories are discussed herein. Currently, we have
      no waiting list or conflicts relative to treatment priorities. We reserve the
      technique for patients with anesthetic contraindications, as case number five.

PMID- 7818301
TI  - [Urethral protrusion caused by blunt trauma of the anterior urethra].
AB  - We report an uncommon case of complete rupture of the anterior urethra secondary
      to blunt trauma, with protrusion of the urethral mucosa through the urinary
      meatus. The singular images of this case are presented and the mechanisms
      involved in this unusual type of lesion are analyzed.

PMID- 7818299
TI  - [Treatment of priapism with phenylephrine].
AB  - Pathological erection may be ascribed to different causes and its treatment
      represents a challenge to the attending urologist. For the past 3 years we have
      utilized intracavernous phenylephrine to treat this condition. Our success rate
      is 93.1%, with detumescence achieved between 30 sec to 15 min. No complications
      have been observed and the responders have referred no changes in their sexual
      activity. We therefore advocate its use before recurring to more aggressive
      maneuvers.

PMID- 7818302
TI  - [Bladder embryonal rhabdomyosarcoma in the adult].
AB  - Embryonal rhabdomyosarcoma of the bladder is a tumor thar presents sporadically
      in the adult patient and its treatment continues to be a controversy. One such
      case is presented herein. The epidemiological and histopathological features of
      this tumor type are described and the different therapeutic approaches advocated
      in the literature are discussed.

PMID- 7818303
TI  - [Kidney trauma with congenital hydronephrosis. Report of a case].
AB  - We report on a 16-year-old patient with stricture of the pyeloureteric junction
      (PUJ) that had been incidentally discovered following trauma to the lumbar
      region. The literature is briefly reviewed.

PMID- 7818304
TI  - [Renal autotransplantation in a case of idiopathic retroperitoneal fibrosis
      refractory to other treatments].
AB  - We report a case of renal autotransplantation in a patient with right
      retroperitoneal fibrosis that had been previously treated by ureterolysis with
      intraperitonization and corticoid therapy without success. The literature is
      briefly reviewed and the therapeutic possibilities in refractory retroperitoneal
      fibrosis are discussed, with special reference to renal autotransplantation.

PMID- 7818305
TI  - [Post-nephrectomy duodeno-cutaneous fistula resolved with parenteral nutrition
      and octreotide (somatostatin analogue)].
AB  - After a right nephrectomy of ischemic kidney, a high-output duodenal fistula
      developed on the third postoperative day. Sixteen days of total parenteral
      nutrition were unsuccessful, so octreotide (a synthetic analogue of somatostatin)
      was added (0.1 mg subcutaneously every 8 hours). The output decreased
      progressively and the fistula closed completely 9 days thereafter.

PMID- 7818306
TI  - [Bladder leiomyoma: report of a case].
AB  - We report a case of leiomyoma of the bladder in a male patient who presented with
      cystitic syndrome and hematuria. The literature is briefly reviewed and the
      benign nature of this condition is underscored. The prognosis is excellent with
      correct treatment.

PMID- 7818307
TI  - [Lithiasis of the prostatic loge].
AB  - Lithiasis may develop in the prostate loge following prostate surgery. Calculus
      formation in the prostate can be ascribed basically to foreign bodies, residual
      adenomatous spheroids and clots or fragments of sphacelous mucosa in the presence
      of a stenotic area after surgery and/or infection. The diagnosis is based on the
      physical examination and particularly on the radiological findings. Treatment is
      by open surgery or endoscopic or extracorporeal lithotripsy.

PMID- 7818308
TI  - [Emphysematous cystitis with inversion of the contrast and urine levels inside a
      bladder diverticulum in computerized tomography].
AB  - We report a case of emphysematous cystitis in a 70-year-old male with acute
      urinary retention. Patient evaluation included a CT scan that disclosed a large
      diverticulum in the bladder and inverted contrast medium-urine level. We discuss
      the possible causes of this unique, paradoxic and infrequent finding, which often
      indicates the presence of infectious sediment in the bladder.

PMID- 7818309
TI  - Bilateral scrotal urinary extravasation in a transplant recipient mimicking acute
      filariasis.
AB  - Urinary leak following renal transplantation is less common nowadays with better
      techniques. Bilateral scrotal extravasation following urinary leak is extremely
      rare. A history of filariasis in an endemic zone could mask and delay the
      diagnosis. One such case is described wherein ureteroneocystostomy was revised
      and the patient could be successfully managed following urinary leak.

PMID- 7818310
TI  - Health status after myocardial revascularization: inferior results in women.
AB  - We followed up 1,335 patients (287 female, 1,048 male) for 2 to 18 years (mean,
      4.3 years) after they had undergone coronary artery bypass grafting. A health
      status index was calculated on the basis of their responses to annual
      questionnaires. The female patients were older (64.1 +/- 0.3 versus 60.4 +/- 0.3
      years) and had a higher incidence of diabetes (28.6% versus 16.1%). The risk
      profile of women was otherwise similar to that of men. The hospital mortality was
      significantly higher in the women, particularly in those younger than age 60. The
      probability of survival (Kaplan-Meier) at 5, 10, and 15 years was lower in female
      patients at each interval. The mean health status index was also lower in women
      at 5, 10, and 15 years, and also lower in all subsets. In nondiabetic patients,
      the hospital mortality and probability of survival at 10 years did not differ
      between the female and male patients. In the diabetic patients, the hospital
      mortality was 11.0% (women) and 3.6% (men); the survival at 10 years was 0.42
      (women) and 0.56 (men) (p < 0.001). Thus, the health status in women is less
      satisfactory than that of men after myocardial revascularization, and the
      probability of survival is lower. The excess mortality in female patients may be
      due to the higher incidence of diabetes in this group.

PMID- 7818311
TI  - Intrapleural perfusion hyperthermo-chemotherapy for malignant pleural
      dissemination and effusion.
AB  - Taking advantage of the antitumor effect of hyperthermia, we administered
      intrapleural perfusion hyperthermo-chemotherapy for the treatment of malignant
      pleural seeding or pleural effusion. This consists of irrigating the pleural
      space for 2 hours with 43 degrees C saline solution containing cis-platinum using
      specially devised extracorporeal circuits. From January 1988 through December
      1993, we performed this technique in 12 patients with malignant disseminated
      lesions stemming from lung cancer who also underwent surgical resection of the
      primary lesions and in 7 patients with malignant pleural effusions who did not
      undergo thoracotomy or surgical resection. There were no serious clinical
      complications associated with this procedure. The pharmacokinetics showed that a
      high concentration of cis-platinum (more than 17.6 micrograms/mL in the free
      form) was retained in the pleural cavity during perfusion. After this therapy,
      the cancer cells showed marked degeneration with fibrosis in the pleural wall.
      The pleural effusion was well controlled in 100% of the patients. The median
      survival time in the 12 patients with pleural disseminated lesions who were
      treated with intrapleural perfusion hyperthermo-chemotherapy was 20 months. On
      the other hand, the median survival time in 7 patients with similar lesions who
      did not receive IPHC was only 6 months. Intrapleural perfusion hyperthermo
      chemotherapy seems to have considerable value as an adjuvant therapy for patients
      with pleural dissemination who have had their primary lesions removed.

PMID- 7818312
TI  - Normothermia versus hypothermia during cardiopulmonary bypass: a randomized,
      controlled trial.
AB  - To evaluate the influence of perfusion temperature on systemic effects of
      cardiopulmonary bypass (CPB), 30 patients undergoing elective coronary artery
      bypass grafting were randomly assigned to either normothermic (warm, n = 14, 36
      degrees C) or hypothermic (cold, n = 16, 28 degrees C) CPB. Serial hemodynamic
      measurements and blood samples were obtained before, during and after the CPB
      procedure. During CPB, there were no differences between both groups in the need
      for vasopressors (norepinephrine, phenylephrine), urinary output, or fluid
      balance. In the early postoperative period, normothermic CPB patients had
      significantly lower systemic vascular resistance and higher cardiac index
      measurements (mean +/- standard error: systemic vascular resistance, 880 +/- 27
      versus 1,060 +/- 57 dyne.s.cm-5, p = 0.025; cardiac index, 3.6 +/- 0.1 versus 2.9
      +/- 0.1 L.min-1.m-2, p = 0.01) without differences in the administration of
      vasoactive drugs. Blood loss was significantly higher in patients after
      hypothermic CPB (median [range] body surface area: 370 [180-560] versus 490 [280
      2,120] mL/m2, p = 0.0006), with a greater need for transfusion of erythrocytes
      and fresh frozen plasma. Plasma levels of tumor necrosis factor and soluble tumor
      necrosis factor receptors increased during and after CPB, independent of
      perfusion temperature. This study suggests a significant influence of CPB
      temperature and respective perfusion management on postoperative hemodynamics and
      blood loss. Normothermic CPB is not associated with additional systemic adverse
      effects.

PMID- 7818313
TI  - Reconstructive airway operation after irradiation.
AB  - After a patient died of anastomotic necrosis following a tracheal resection for
      the management of recurrent thyroid cancer invading the trachea, which had been
      treated 6 years previously by thyroid lobectomy and 4,800 cGy of radiation to
      control known residual disease, we explored methods to promote the healing of
      tissues damaged by irradiation. Between 1979 and 1992, 22 patients underwent
      major airway resection and reconstruction after receiving large doses of
      radiation. The average dose was 4,979 +/- 1,113 cGy (range, 3,150 to 6,840 cGy);
      the number of fractions, 20 to 38; and the average dose per fraction, 180 cGy
      (range, 150 to 200 cGy). The interval between irradiation and surgical treatment
      was 42 +/- 105 months (range, 1 to 480 months). Seven cervical, eight
      midtracheal, and five carinal resections were performed, as well as two mainstem
      sleeve resections. Omentum was used to protect the anastomosis in 15 patients
      (68%), a pericardial fat pad was used in 2, and pleura was used in 2. In 3
      patients, sternohyoid muscle was placed between the anastomosis and a major
      vascular structure, but without a tissue wrap. Two patients (9.0%) died
      postoperatively. Anastomotic dehiscence was the cause of death in a patient
      treated for lymphoma, and adult respiratory distress syndrome was the cause in
      the other patient; this patient had undergone carinal pneumonectomy.
      Complications developed in 8 patients (36%). Two cervical dehiscences were
      treated by T-tube placement, 2 patients suffered wound infection, and 1 patient
      each suffered a myocardial infarction, dysphagia, hemoptysis, and
      bronchitis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7818314
TI  - Preoperative vein mapping for coronary artery bypass operations.
AB  - High-resolution, real-time ultrasonographic imaging of the greater saphenous
      veins was performed preoperatively in 100 patients undergoing coronary artery
      bypass grafting. Vein diameters were measured by ultrasound at four locations in
      the leg, and the course of the vein in the leg was marked on the overlying skin.
      Veins removed at operation were measured at the same locations at initial
      dissection and after vein preparation. The mapped and in situ vein diameters
      correlated closely, whereas the distended vein diameter was approximately 1.5 mm
      larger. When greater saphenous veins were absent or diseased, lesser saphenous
      veins were mapped. No differences in measurements were demonstrated for a variety
      of patient and operator variables. Major branches or duplications were predicted
      correctly in 11 patients and venous disease in 13 patients. Mapping influenced
      the surgeon's choice of the venectomy site in 13 patients. Vein mapping is a
      simple, accurate, and noninvasive method of imaging the saphenous vein
      preoperatively. It is useful in demonstrating areas of venous anomalies and
      disease, and predicts the course of the vein in the leg.

PMID- 7818315
TI  - Postoperative flow characteristics of left internal thoracic artery grafts.
AB  - Twenty patients whose left internal thoracic artery (LITA) was anastomosed to the
      left anterior descending artery (LAD) underwent postoperative coronary
      angiography and Doppler ultrasound velocimetry. During angiography, the diameter
      of the LITA conduit was measured at three points: proximal, mid, and distal. The
      degree of left anterior descending artery stenosis proximal to the anastomotic
      site was evaluated by densitometry. The LITA flow velocity pattern was obtained
      at the three points to calculate the total, systolic, and diastolic flow volume.
      There were significant differences in the total LITA flow among the three points
      (proximal, 36.0 +/- 17.2 mL/min; mid, 29.9 +/- 15.2 mL/min; distal, 27.2 +/- 14.0
      mL/min; p < 0.001 between the proximal and the mid or distal portions). The
      degree of left anterior descending artery stenosis affected the distal LITA flow
      and diameter (r = 0.823 and 0.811, respectively). There were significant
      differences in the systolic LITA flow among the three points (proximal, 13.2 +/-
      6.5 mL/min; mid, 8.1 +/- 4.7 mL/min; distal, 5.6 +/- 3.4 mL/min; p < 0.001
      between the proximal and the mid or distal portions). However, there was no
      statistically significant difference in the diastolic LITA flow among the three
      points (proximal, 22.9 +/- 11.0 mL/min; mid, 21.7 +/- 10.8 mL/min; distal, 21.6
      +/- 10.8 mL/min). We conclude that a lower degree of LAD stenosis significantly
      reduces the LITA flow, inducing the string phenomenon. Additionally, during the
      diastolic phase, the LITA graft transports the blood primarily to the coronary
      artery but not to the side branches. Therefore, the steal phenomenon might not
      apply in the setting of an LITA graft.

PMID- 7818316
TI  - Anatomic study of the collateral blood supply of the sternum.
AB  - A microdissection study was carried out on ten injected, cleared human sternal
      specimens. Three types of vessel were identified that have the potential to carry
      blood to the sternum after mobilization of the internal thoracic artery (ITA):
      (1) branches of the ITA that supply both the sternum and the pectoralis major
      ("sternal/perforating branches"), (2) branches of the ITA that supply both the
      sternum and an adjoining intercostal space ("sternal/intercostal branches"), and
      (3) posterior intercostal arteries that do not anastomose with an ITA branch but
      continue past the ITA to reach the sternum. All three types of vessel were found
      more frequently in the proximal than in the distal half of the sternum. For
      sternal/perforating and sternal/intercostal vessels to function as collaterals
      after ITA bypass grafting, their short common trunks of origin must remain
      intact. The data support the recommendation that the branches of the ITA be
      ligated as close as possible to the ITA itself to preserve collateral blood flow
      to the sternum.

PMID- 7818317
TI  - Deferoxamine cardioplegia reduces superoxide radical production in human
      myocardium.
AB  - Recent studies have demonstrated enhanced myocardial protection during ischemia
      using the oxygen free radical scavenger, deferoxamine. This effect of
      deferoxamine may be related either to its iron-chelating property or to
      intervention in an iron-independent mechanism. We tested the latter by
      determining the rate of superoxide anion production and the degree of lipid
      peroxidation in human myocardial tissue after including deferoxamine in
      cardioplegic solution. Fourteen patients who underwent aortic, mitral, or double
      valve replacement were included in the study. The mean value for superoxide
      radical production was 59.8 +/- 17.0 nmol.min-1.g-1 for the control group (group
      C; n = 7) and 21.3 +/- 8.1 (p < 0.001) for the deferoxamine-treated group (group
      D; n = 7). The mean value for thiobarbituric reactive substances was 80.00 +/-
      23.4 in group C and 38.7 +/- 23.8 nmol.min-1.g-1 in group D (p < 0.01). In
      conclusion, deferoxamine appears to have a moderating effect on the biochemical
      markers of ischemia reperfusion injury. Its scavenging effect on superoxide anion
      could play a role in the cellular defense against oxygen radicals during cardiac
      operations.

PMID- 7818318
TI  - Pneumonectomy after contralateral lobectomy: is it reasonable?
AB  - Conservative resection of a second primary lung cancer is desirable but not
      always feasible. We recently carried out three left pneumonectomies for the
      removal of metachronous primary lung cancers in patients who had previously
      undergone right upper lobe resection for the treatment of bronchogenic carcinoma.
      In each patient, the results of pulmonary function tests plus the findings from
      quantitative perfusion lung scans predicted a postpneumonectomy forced expiratory
      volume in 1 second of at least 1.00 L. All 3 patients had uncomplicated
      postoperative courses, and were doing satisfactorily at follow-up 2 to 6 months
      later. One patient died 5 months after pneumonectomy due to unrelated causes,
      another died 8 months after pneumonectomy from infection after resection of a
      brain metastasis, and the third is doing well 15 months after pneumonectomy. The
      rarity of previously reported cases suggests that performing a pneumonectomy
      after contralateral lobectomy may be considered too radical. Our experience
      indicates the procedure may be considered if the patient's pulmonary function
      meets the standard criteria for pneumonectomy.

PMID- 7818319
TI  - Shed whole blood autotransfusion during aortic aneurysm operation with a modified
      collection infusion system.
AB  - We describe a modified shed whole blood collection and autotransfusion system
      that allows several options for the processing and autotransfusion of shed blood:
      use of the Cell Saver (Haemonetics, Braintree, MA) or the ultrafiltration of
      collected blood, and the autotransfusion of unprocessed shed whole blood. The
      system has proved useful for transfusion in the setting of thoracic aortic
      operations, and we describe here our experience in 5 patients undergoing
      resection of a descending thoracic aortic aneurysm in whom this system was used.

PMID- 7818320
TI  - Mitral valve replacement with a collar-reinforced prosthetic valve for disrupted
      mitral annulus.
AB  - The mitral valve was replaced with a collar-reinforced prosthetic valve in 6
      patients with a disrupted mitral annulus, in 3 because of infective endocarditis,
      including 2 patients with prosthetic valve endocarditis, in 2 because of a
      severely calcified mitral annulus, and in 1 who had previously undergone mitral
      valve replacement twice. Four patients had undergone prior mitral operations;
      these consisted of mitral valve replacement in 3 patients and mitral valve repair
      in 1. In all patients, the prosthesis was secured by double-layered sutures, with
      the first row of buttressed sutures passing through the leaflet or sutured to the
      left ventricular muscle and through the sewing cuff of the prosthetic valve. The
      second row of running sutures was then placed through an extended annular equine
      pericardial cuff of the prosthetic valve and the supraannular left atrial wall.
      In 2 patients, all chordae tendineae were preserved to maintain annulopapillary
      muscle continuity. All patients survived and have remained well for a mean of
      22.3 months. There has been no prosthetic valve dehiscence, except for minimal
      paraprosthetic leakage in 1 patient. These results demonstrate that mitral valve
      replacement in patients with a disrupted mitral annulus can be successfully
      accomplished with a collar-reinforced prosthetic valve.

PMID- 7818321
TI  - Aortic arch operation: current treatment and results.
AB  - Between January 13, 1987, and December 31, 1993, 227 patients were treated
      surgically for aortic disease involving the transverse aortic arch. Forty-eight
      patients (21.14%) had acute aortic dissection (group A), 69 (30.40%) had chronic
      dissection (group B), and 110 (48.46%) had nondissecting fusiform or saccular
      aneurysms (group C). The replacement of the transverse arch involved 194 graft
      replacements, 27 elephant trunk procedures, and 6 patch graft repairs.
      Concomitantly, 22 patients had aortic valve resuspension, 18 patients had
      composite valve graft insertions, and 75 had separate aortic valve replacement.
      The frequency of prior cardiac operation was 20.83% (10 patients) in group A,
      69.57% (48 patients) in group B, and 15.45% (17 patients) in group C. Profound
      hypothermic circulatory arrest was used in all patients during their transverse
      arch procedures. The mean circulatory arrest times (in minutes) were 29.18 +/-
      1.39, 36.62 +/- 1.91, and 29.25 +/- 1.46 for groups A, B, and C, respectively.
      Retrograde cerebral perfusion through the superior vena cava cannula was used in
      111 (48.9%) patients during the circulatory arrest period. In-hospital mortality
      was 6.17% (14 deaths). Long-term follow-up was 100% complete. There were 20 late
      deaths, with a long-term mortality rate of 9.26% (20/216).

PMID- 7818322
TI  - Potential use of the intercostal artery as an in situ graft: a cadaveric study.
AB  - The third to eighth intercostal arteries (ICAs) were bilaterally dissected in 10
      cadavers to assess their length and possible routes to coronary arteries if used
      as in situ grafts. The mean lengths for the intercostal arteries harvested were
      27.0 +/- 2.9 cm on the left and 27.4 +/- 3.2 cm on the right. The shortest
      anatomic route to the coronary arteries of the in situ ICAs harvested was medial
      to the lung and either superior to or inferior to the hilum. By using either the
      superior or inferior routes in situ ICAs were long enough to reach the major
      coronary artery territories in all cadavers. The most suitable ICAs for grafting
      the coronary arteries and the shortest routes were as follows: left anterior
      descending--left fifth ICA by inferior route; circumflex coronary artery-left
      fifth ICA by inferior route; and right coronary artery-right seventh ICA by
      inferior route. We conclude that it is anatomically feasible to use the
      intercostal artery as an in situ graft in coronary artery operation.

PMID- 7818323
TI  - Early and long-term results after completion pneumonectomy.
AB  - From January 1, 1978 to December 31, 1992, 37 patients underwent a completion
      pneumonectomy after a previous lobectomy (36 men and 1 woman; mean age, 60 years;
      range, 41 to 77 years). These account for 4.8% of 758 pneumonectomies. The
      purpose of the present study was to evaluate the operative results of completion
      pneumonectomy and long-term survival in patients with bronchogenic cancer. The
      initial lung resection had been performed for primary bronchogenic cancer in 23,
      metastatic thyroid adenocarcinoma in 1, and benign diseases in 13 (tuberculosis
      in 11, aspergilloma in 1, and bronchiectasis in 1). Completion pneumonectomy was
      required for bronchogenic cancer in 32 (15 stage I, 6 stage II, 11 stage III).
      One patient had relapsing metastatic thyroid carcinoma, 2 had bronchiectasis, and
      2 had a venous infarction after lobectomy. Four patients (10.8%) died
      perioperatively of the following causes: 1 fatal intraoperative bleeding, 1 fatal
      postoperative bleeding, 1 pneumonia, and 1 malignant hypercalcemia. Median
      operative blood loss was 1,000 mL, and 19 patients experienced bleeding exceeding
      1,000 mL (51%). Six patients had intraoperative vascular injury. Nonfatal
      surgical complications occurred in 9 patients (24%), including 5 clotted
      hemothoraces, 3 empyemas, and 1 bronchopleural fistula. Four patients had medical
      complications (2 pulmonary edemas, 1 sinus tachycardia, and 1 unexplained fever).
      Twenty-three had an uneventful straightforward recovery (62%).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7818324
TI  - Left ventricular outflow tract obstruction in TGA: treatment with LV-to-PA valved
      conduit.
AB  - Progressive or recurrent left ventricular outflow tract obstruction after a
      previous Mustard or Senning operation represents a rare but challenging problem.
      The obstruction can be resected in some patients, but abnormal attachment of the
      mitral valve or a long fibromuscular tunnel represents a difficult surgical
      problem. Between 1979 and 1993, we encountered this type of left ventricular
      outflow tract obstruction in 10 patients, 4 to 13 years after the atrial repair.
      They ranged in age from 5 to 15 years (mean, 8.8 years) and weighed between 11.5
      and 47 kg (mean, 25.3 kg). Operations were performed through a left thoracotomy
      with the patient on hypothermic cardiopulmonary bypass but without aortic cross
      clamping. The left atrial appendage and descending aorta were cannulated. Good
      relief of the gradient was obtained in all patients (mean residual gradient, 14.8
      mm Hg). All patients survived the operation. One patient died suddenly at home 6
      months later; 2 patients required conduit replacement. All 9 long-term survivors
      are asymptomatic as of 6 months to 8 years after their conduit placement or
      replacement. We recommend the placement of a left ventricle-to-pulmonary artery
      valved conduit for the relief of severe left ventricular outflow tract
      obstruction arising after a Senning or Mustard operation that cannot be managed
      by other means.

PMID- 7818325
TI  - Isolated lung perfusion with FUDR is an effective treatment for colorectal
      adenocarcinoma lung metastases in rats.
AB  - Currently, the only treatment capable of significantly prolonging survival in
      patients with isolated pulmonary metastases from colorectal adenocarcinoma is
      complete resection. Systemic chemotherapy has been shown to provide little
      benefit. We evaluated the efficacy of highdose, organ-specific 2'-deoxy-5
      fluorouridine (FUDR) using a model of isolated single-lung perfusion (ILP) in the
      rat. On day 0, 28 BDIX rats were inoculated intravenously with 10(6) viable Sp-5
      colorectal adenocarcinoma cells. On day 10 after-tumor inoculation, animals were
      randomized into five treatment groups. Group I received a continuous intravenous
      infusion of FUDR (1 mg.kg-1.d-1) for 7 days administered by an osmotic minipump.
      Group II underwent isolated left lung perfusion with a buffered Hespan solution,
      groups III to V underwent ILP with 3.5, 7, and 14 mg of FUDR per milliliter of
      the buffered Hespan solution, respectively. Animals undergoing ILP were
      anesthetized with pentobarbital, intubated, and ventilated, and then underwent
      left thoracotomy with cannulation of the pulmonary artery; the pulmonary artery
      and vein were clamped proximally. Groups II to V were perfused for 20 minutes at
      a rate of 1 mL/min, followed by a 5-minute washout with FUDR-free buffered Hespan
      solution. On day 26 after tumor inoculation, the animals in all groups were
      sacrificed and their lungs were stained and counted. Animals that underwent ILP
      with 14 mg of FUDR per milliliter of the buffered Hespan solution showed a
      significant decrease in the number of tumor nodules on the treated side versus
      the number on the untreated side (455.2 +/- 87.3 versus 11 +/- 6.4; p <
      0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7818326
TI  - Impact of radical systematic mediastinal lymphadenectomy on tumor staging in lung
      cancer.
AB  - The extent of lymphadenectomy in the treatment of non-small cell lung cancer is
      still a matter of controversy. While some centers perform mediastinal lymph node
      sampling with resection of only suspicious lymph nodes, others recommend a
      radical, systematic mediastinal lymphadenectomy (LA) to improve survival and
      achieve a better staging. Herein we report on the impact of LA on tumor staging
      in a controlled, prospective, randomized clinical trial comparing lymph node
      sampling and LA in a total of 182 patients with operable non-small cell lung
      cancer. Regardless of the type of lymphadenectomy performed, the percentage of
      patients with pathologic N1 or N2 (sampling: n = 23, 23.0%; LA: n = 22, 26.8%)
      disease was very similar in both groups, indicating that systematic radical
      lymphadenectomy is not an essential prerequisite to determine the N stage of a
      patient. In contrast, the number of patients detected to have lymph node
      involvement at multiple levels was significantly increased by LA. In the lymph
      node sampling group only 4 of 23 patients (17.4%) with N2 disease were found to
      have more than one lymph node level involved, whereas LA results in the detection
      of excessive N2 disease in 12 of 21 patients (57.2%; p = 0.007), which was
      associated with a shorter distant metastases-free (p = 0.021) and overall
      survival. In conclusion, LA is not essential to determine the N stage of a
      patient, but results in a more detailed staging of the N2 region, which is of
      prognostic significance. Therefore, it might be useful to identify patients with
      a higher risk for tumor relapse.

PMID- 7818327
TI  - Tumor implants after thoracoscopic resection of a metastatic sarcoma.
AB  - Tumor implantation after video-assisted thoracic operations is rare. We describe
      the case of a 61-year-old woman who underwent an apparently uneventful
      thoracoscopic resection of a solitary pulmonary metastasis from a primary limb
      sarcoma. Within 3 months, extensive trocar and diaphragmatic implants developed
      that required an extensive en bloc resection of her chest wall, diaphragm, and
      lung. Because of the aggressive biologic behavior of sarcomas and their potential
      to grow in surgical tracts, concern is raised about the advisability of using
      video-assisted thoracic surgical techniques in the management of these tumors.

PMID- 7818328
TI  - Anterior pulmonary translocation for repair of truncus arteriosus with
      interrupted arch.
AB  - A newborn was found to have truncus arteriosus and an interrupted aortic arch,
      and underwent primary repair. The patient did well initially, but, by 8 weeks
      postoperatively, showed evidence of severe compression of the right pulmonary
      artery. At reoperation, the pulmonary artery was found to be compressed by a
      large aortic root (truncal root) and the retroaortic area was narrowed. The
      pulmonary artery bifurcation was therefore translocated anteriorly to alleviate
      the compression.

PMID- 7818329
TI  - Kent bundle visualized in situ at operation after unsuccessful radiofrequency
      ablation.
AB  - Kent bundles are seldom visualized at operation, but, in the patient described,
      the pathway was subepicardial, running superficial to the right coronary artery.
      This was probably why radiofrequency ablation failed. When this unusual pathway
      course is encountered, the epicardial approach should be used at operation.

PMID- 7818330
TI  - Lobectomy in the treatment of the scimitar syndrome.
AB  - The scimitar syndrome is a congenital anomaly that consists mainly of total or
      partial anomalous venous drainage of the right lung to the inferior vena cava. We
      report the case of an 8-year-old girl diagnosed at birth as having a scimitar
      syndrome and who presented with recurrent right lower lung infections. She
      underwent resection of the lower half of her right lung without diversion of the
      anomalous venous drainage of the upper portion of the lung. She improved rapidly
      postoperatively and the shunt fraction diminished.

PMID- 7818331
TI  - Recurrent spontaneous perforation of the esophagus.
AB  - Boerhaave's syndrome is uncommon and its precise etiology is unclear. Information
      regarding the long-term outcome of patients surviving this injury is lacking. We
      present the case of a patient who suffered two spontaneous perforations of the
      esophagus that occurred 30 years apart.

PMID- 7818332
TI  - Mitral valve replacement after previous right pneumonectomy.
AB  - Adequate exposure of the mitral valve is essential to the safe and effective
      performance of valve replacement. We describe a successful mitral valve
      replacement performed in a patient who had undergone a right pneumonectomy. After
      a median sternotomy was made, the mitral valve was approached through an incision
      in the left atrial appendage that extended to the origin of the left superior
      pulmonary vein. The operation was uncomplicated, and the patient made an
      uneventful recovery.

PMID- 7818333
TI  - Left ventricular-coronary sinus shunt through a septal aneurysm after mitral
      valve re-replacement.
AB  - We describe a case in which a left ventricular-coronary sinus communication
      through a dissecting ventricular septal aneurysm developed after a redo mitral
      valve replacement. The outlet orifice of the communication was located in the
      side wall of the ostium of the coronary sinus. Both the communication and the
      aneurysm were successfully dealt with by performing a right atriotomy and by
      opening the aneurysm from its outlet orifice.

PMID- 7818334
TI  - Superior vena cava syndrome caused by aneurysm of the innominate artery.
AB  - Isolated aneurysms or ruptures of the innominate artery are rare causes of the
      superior vena cava syndrome. We report on a patient who suffered an isolated
      acute expansion and rupture of an innominate artery aneurysm that precipitated a
      dramatic superior vena cava syndrome. Immediate repair using modern surgical
      techniques, cardiopulmonary bypass, profound hypothermia, circulatory arrest, and
      a Dacron graft rapidly cured the patient of this deadly syndrome.

PMID- 7818335
TI  - Tetralogy of Fallot with anomalous origin of the right coronary artery.
AB  - This report describes a child with tetralogy of Fallot and acquired pulmonary
      valve atresia in whom the pulmonary blood flow was provided solely by retrograde
      flow from an anomalous right coronary artery originating from the main pulmonary
      artery. Complete repair with preservation of the native pulmonary valve and
      implantation of the right coronary artery into the ascending aorta is described.

PMID- 7818336
TI  - Spontaneous hemothorax caused by a chest wall chondrosarcoma.
AB  - A 48-year-old man who presented with chest pain was found to have a spontaneous
      hemothorax caused by a large grade II chondrosarcoma. This was diagnosed on the
      basis of the findings from thoracotomy. After chest tube drainage of the
      hemothorax, the tissue obtained by two computed tomography-guided biopsies of a
      residual mass did not yield findings that allowed diagnosis of the tumor. This
      unusual case illustrates the importance of a systematic workup whenever a
      spontaneous hemothorax is encountered.

PMID- 7818337
TI  - Occlusion of the left coronary ostium due to fusion of the aortic cusp to the
      wall.
AB  - We report on a patient with occlusion of the left coronary ostium and aortic
      regurgitation due to fusion of the left aortic cusp to the aortic wall. The left
      coronary flow was restored by excision of the adherent left aortic cusp and
      aortic valve replacement.

PMID- 7818338
TI  - Pneumocephalus complicating routine thoracotomy: symptoms, diagnosis and
      management.
AB  - Pneumocephalus resulting from a subarachnoid-pleural fistula most commonly occurs
      after trauma. Such a complication is very rarely seen after thoracotomy alone,
      with 15 cases reported to date in the literature. We report a case of
      pneumocephalus and subarachnoid-pleural fistula that developed secondary to
      thoracotomy. It was diagnosed by postmyelography computed tomography and treated
      with open surgical repair after a trial of conservative therapy failed. The
      presenting symptoms and signs, diagnostic methods, and options for therapy are
      reviewed.

PMID- 7818339
TI  - Thoracoscopic removal of mediastinal parathyroid adenoma.
AB  - Mediastinal parathyroid tissue hyperfunctions in as much as 25% of the patients
      with primary hyperparathyroidism, and this may be responsible for causing
      conventional operative procedures to fail in as much as one-third of the cases.
      When lesions prove to not be accessible through a cervical incision, or when a
      mediastinal adenoma is diagnosed before cervical procedures, median sternotomy
      and angiographic ablation have been considered the only options for removal.
      However, thoracoscopy has theoretic advantages over both. Two patients underwent
      successful thoracoscopic removal of a hyperfunctioning ectopic mediastinal
      parathyroid adenoma and their cases are presented here.

PMID- 7818340
TI  - Subdiaphragmatic implantation of implantable cardioverter defibrillator
      generator.
AB  - Despite several improvements in the surgical technique and in the technologic
      design of cardioverter defibrillators made over the past years, abdominal
      placement of the generator device, done as Mirowski did it in his first
      implantation performed in 1980, remains the widely used method. Although smaller
      defibrillators are available, they remain bulky and are a source of local
      complications. To prevent such complications and to enhance patient comfort, we
      performed a subdiaphragmatic implantation in 31 patients.

PMID- 7818341
TI  - Aortic paravalvular leaks: alternative suture placement strategy for the left
      coronary cusp.
AB  - Repair of a left coronary cusp aortic paravalvular leak can be achieved by
      placing stitches through the main pulmonary artery, right pulmonary artery, and
      left atrium when removal of the previously inserted valve is contraindicated.

PMID- 7818342
TI  - Prevention of spinal cord injury after repair of the thoracic or thoracoabdominal
      aorta.
AB  - Spinal cord injury occurring as the result of surgical repair of thoracic and
      thoracoabdominal aortic disease remains a devastating complication. The incidence
      of postoperative neurologic deficits varies from 4% to 38%. Factors associated
      with a greater risk for injury include the presence of dissection or extensive
      thoracoabdominal disease, and a prolonged cross-clamp time. Spinal cord ischemia
      initiates a deleterious cascade of biochemical events that ultimately result in
      an increased intracellular calcium concentration. Calcium-activated proteases,
      lipases, and nucleases mediate the processes that cause cell injury. The
      accumulation of oxygen-derived free radicals and the occurrence of hyperemia
      during reperfusion are also contributing causes of spinal cord injury. Increasing
      the spinal cord blood flow with shunts, oxygenated bypass circuits, cerebrospinal
      fluid drainage, the intrathecal administration of vasodilators, and the
      reattachment of intercostal arteries has been tried in an effort to increase
      spinal cord perfusion. Pharmacologically based measures to prevent spinal cord
      injury have been pursued, and these have consisted of hypothermia, anesthetic
      agents, calcium channel blockers, free radical scavengers, and immune system
      modulation. However, no single technique has proved to be consistently effective
      in preventing ischemia-induced spinal cord injury.

PMID- 7818343
TI  - Update in myocardial protection.

PMID- 7818344
TI  - 1987: Anterolateral thoracotomy as an alternative to repeat median sternotomy for
      replacement of the mitral valve. Updated in 1995.

PMID- 7818345
TI  - Spontaneous pneumothorax in single-lung transplantation: finding a common
      treatment.

PMID- 7818346
TI  - Alternative heart transplantation technique.

PMID- 7818347
TI  - A solution to prolonged air leak after video-assisted thoracoscopic lobectomy.

PMID- 7818348
TI  - Modified Fang's approach for spinal lesion situated at the level of T2-T3
      vertebrae.

PMID- 7818349
TI  - Heart transplantation and primary cardiac tumors.

PMID- 7818350
TI  - Enlargement of the right atrium associated with dermatomyositis.

PMID- 7818351
TI  - Intraoperative autohemotransfusion and open heart reoperation.

PMID- 7818352
TI  - Cutaneous lentigines, freckles, and atrial myxomas.

PMID- 7818353
TI  - Reduction aortoplasty for moderate-sized ascending aortic aneurysms.

PMID- 7818354
TI  - Compensatory growth of porcine right lungs after chronic rejection of
      transplanted left lungs.
AB  - Neonatal lung hypoplasia is frequently a fatal condition often associated with
      congenital diaphragmatic hernia. Unilateral lung transplantation rarely has been
      performed for this indication, although it is a potential solution. It is not
      known whether the transplant needs to function permanently or to act as a bridge
      until the native lung develops. It is also not known whether the native lung will
      grow in the face of an immunosuppressed state and chronic rejection of the
      transplanted lung. We therefore developed a porcine model of left lung rejection
      to study this. Infant swine underwent left lung transplantation. Chronic
      rejection occurred in all, resulting in nonfunction of the transplanted lung. The
      right lungs of these animals were compared with the right lungs of size-matched
      and age-matched control animals not given immunosuppressive treatment and not
      undergoing transplantation. There were no differences in terms of the functional
      residual capacity, airway compliance, and airway resistance among the groups.
      There was a significant increase in the pulmonary vascular resistance in the
      animals with transplanted lungs. There was also a significant increase in the
      lung weight in these animals. Unilateral pneumonectomies were done in 4 infant
      pigs to serve as controls. Three of the 4 did not survive the operation because
      of acute pulmonary failure. In conclusion, the study group exhibited evidence of
      compensatory growth that was not seen in the control animals, as shown by the
      increase in lung weight. This suggests that contralateral lung growth occurs in a
      growing animal, despite the effects of immunosuppression therapy and chronic
      rejection of the transplanted lung.

PMID- 7818355
TI  - Repair of coarctation of the aorta in neonates and infants: a thirty-year
      experience.
AB  - Between January 1962 and December 1991, 179 children less than 1 year of age
      underwent repair of coarctation of the aorta. Group I (1962 to 1971) consisted of
      19 patients, group II (1972 to 1981) of 57 patients, group III (1982 to 1991) of
      103 patients. Neonates (< 30 days old) made up 60% of group I, 57% of group II,
      and 70% of group III. The proportion of infants with associated complex cardiac
      abnormalities was 7% in group I, 25% in group II, and 39% in group III.
      Techniques of repair included resection with end-to-end anastomosis (n = 65),
      subclavian flap repair (n = 85), patch aortoplasty (n = 18), and other procedures
      (n = 11). The early mortality (< 30 days) was lowest in group III (group I, 21%;
      group II, 21%; and group III, 7%; p < 0.05), but the late mortality was similar
      in all groups (group I, 11%; group II, 13%; and group III, 15%). The overall
      actuarial survival was 57.7% +/- 0.15% at 27.1 years in group I, 65.7% +/- 0.07%
      at 19.7 years in group II, and 77.5% +/- 0.04% at 9.3 years in group III (p = not
      significant). Twenty-five restenoses requiring intervention occurred in 23
      patients, for an overall restenosis rate of 16.4%. The incidence of restenosis
      was 23% for the patients who underwent end-to-end anastomosis, 11% for those who
      underwent subclavian flap repair (p < 0.1), and 27% for those who underwent patch
      aortoplasty (p < 0.01). Balloon angioplasty was successful in relieving 11 of the
      12 restenoses in groups II and III.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7818356
TI  - Thoracoscopic implantation of cancer with a fatal outcome.
AB  - A case is presented in which an indeterminate lung lesion was extracted through
      an accessory incision during a video-assisted thoracic surgical lung biopsy. The
      lesion was malignant, and a completion lobectomy was performed. An incisional
      recurrence developed 5 months later, and this was treated with a wide chest wall
      resection and reconstruction. However, there was a second massive chest wall
      recurrence that proved fatal. We believe that tumor seeding to the chest wall
      occurred at thoracoscopy. To prevent such tumor seeding, thoracoscopic biopsy
      specimens should be removed in some sort of receptacle when cancer is suspected.

PMID- 7818357
TI  - Clinical study of normothermic cardiopulmonary bypass in 100 patients with
      coronary artery disease.
AB  - During normothermic cardiopulmonary bypass (CPB), the body temperature is
      maintained at 37 degrees C. Since 1987, it has been our standard practice to use
      normothermic CPB in our patients undergoing a cardiac operation, and our
      experience now consists of more than 3,000 consecutive patients. Myocardial
      protection is achieved through the combination of cold intermittent antegrade
      blood cardioplegia, no topical cooling, and a terminal "hot shot" of blood
      cardioplegia. We disagree with the stance of the Toronto group that normothermic
      CPB requires the administration of large volumes of cardioplegic and crystalloid
      solutions and the frequent use of phenylephrine hydrochloride to ensure a low
      systemic vascular resistance. To establish a routine technique of cold heartwarm
      body bypass, we conducted a clinical study in 100 consecutive patients with
      coronary artery disease. We found that the total cardioplegia volume needed in
      our patients was 1,946 +/- 257 mL, versus 4,700 +/- 1,900 mL in the Toronto
      study, and an additional crystalloid volume loading of 400 +/- 141 mL during CPB
      was needed in 26% of our patients, versus a total volume of 3,650 +/- 800 mL in
      the Toronto series. Phenylephrine (250 micrograms) was used in 16% of our
      patients, versus 88% of the patients in the Toronto study (mean dose, 1.3 mg).
      During normothermic CPB, the mean radial arterial pressure was 57.3 +/- 9.4 mm
      Hg.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7818358
TI  - Mitral valve replacement with complete retention of native leaflets.
AB  - Although both mitral leaflets contribute equally to the preservation of left
      ventricular function after mitral valve replacement, most surgeons routinely
      excise the anterior mitral leaflet. Possible disadvantages of leaflet retention
      are left ventricular outflow tract obstruction and interference with prosthetic
      valve motion. In 31 patients undergoing mitral valve replacement, all mitral
      valvular and subvalvular tissue was completely retained using a technique that
      involved reefing the native leaflets into the valve sutures. Fifteen Carpentier
      Edwards porcine and 16 St. Jude Medical valves were implanted. Two patients died
      of causes unrelated to this technique. In the others, echocardiography
      demonstrated either no or an insignificant left ventricular outflow tract
      gradient, and, in most, no valvular tissue could be seen in the left ventricular
      outflow tract. No interference with prosthetic leaflet mobility occurred. The
      salutary results of mitral valve replacement with complete leaflet retention
      recommend its use.

PMID- 7818359
TI  - Isolated cleft mitral valve: valve reconstruction techniques.
AB  - Reports concerning an isolated cleft of the anterior mitral valve are rare. This
      congenital anomaly of the mitral valve is usually repaired by suturing the edges
      of the cleft. We report 4 cases of isolated anterior mitral cleft. The patients
      ranged in age from 13 to 41 years. The clinical symptoms were those typical of
      mitral insufficiency. In all 4 patients, preoperative echocardiography was able
      to establish the exact anatomic diagnosis. In 1 patient, the cleft was directly
      sutured, whereas, in the other 3 patients, a fibrous reaction of the edges of the
      cleft with a subsequent lack of valvular tissue made direct suture technically
      impossible. Instead, the fibrous edges of the cleft were resected and the
      anterior leaflet of the mitral valve was reconstructed using an autologous
      pericardial patch pretreated with buffered glutaraldehyde. All 4 patients
      underwent annuloplasty together with placement of a Carpentier mitral ring.
      Postoperative echocardiograms have confirmed good results of the repair; 1
      patient has a trivial insufficiency and 3 have a completely competent mitral
      valve.

PMID- 7818360
TI  - Inadequacy, mortality, and thoracoscopy.

PMID- 7818361
TI  - The fate of homograft conduits in children with congenital heart disease: an
      angiographic study.
AB  - The use of homograft conduits in the repair of congenital heart disease is widely
      accepted. We reviewed the catheterization and angiographic data from 20 patients
      with homograft conduits. All conduits were to the pulmonary arteries. The age at
      operation was 4.7 +/- 5.6 years (mean +/- standard deviation) and at follow-up
      catheterization, 7.8 +/- 6.7 years. At implantation, conduit cross-sectional area
      and Z value were 219 +/- 96 mm2 and 3.5 +/- 1.8, respectively. At subsequent
      catheterization, the conduit diameters were measured in two projections at the
      shaft, annulus, valve opening, and insertion into the pulmonary artery. The
      transconduit gradient was 47 +/- 26 mm Hg. The cross-sectional areas were 149 +/-
      56 mm2 at the shaft, 151 +/- 92 mm2 at the annulus, 108 +/- 116 mm2 at the valve
      opening, and 127 +/- 84 mm2 at the pulmonary artery insertion. The Z values were 
      0.9 +/- 2.5, -0.9 +/- 2.8, -3.8 +/- 4.0, and -2.0 +/- 3.4, respectively. The
      cross-sectional areas and the Z values at the levels of measurement were
      significantly smaller than the corresponding values at implantation. The change
      in cross-sectional areas and Z values exceeded what would be expected from growth
      alone. These data indicate that there is a decrease, with time, in the functional
      lumen of homograft conduits, and this may have implications for follow-up
      strategy after implantation.

PMID- 7818362
TI  - Neutrophil modulation results in improved pulmonary function after 12 and 24
      hours of preservation.
AB  - Neutrophils are important mediators of reperfusion injury, and suppression of
      neutrophil function or numbers can reduce reperfusion injury and improve long
      term organ preservation in transplantation. NPC 15669, a leumedin, is a novel
      compound that prevents recruitment of neutrophils at inflammatory foci by
      inhibiting CD11b/CD18 adhesion molecule expression. NPC 15669 was used to inhibit
      neutrophil adhesion during reperfusion of isolated rabbit lungs after 12 and 24
      hours of cold storage. Lungs (New Zealand White male rabbits, 2 to 3 kg) were
      flushed with 4 degrees C Euro-Collins (EC) solution, harvested en bloc, stored
      under various study conditions, and reperfused for 3 hours with fresh whole blood
      at 37 degrees C in an isolated perfusion system at constant flow and an inspired
      oxygen fraction of 1. Four groups (n = 6 each) were studied. Group I underwent
      immediate whole blood reperfusion. Group II were stored for 12 hours in 4 degrees
      C EC solution before reperfusion. Group III were stored for 12 hours in 4 degrees
      C EC solution and reperfused with whole blood containing NPC 15669 (10 mg/kg
      whole body weight). Group IV were stored for 24 hours in 4 degrees C EC solution
      and reperfused with whole blood containing NPC 15669 (10 mg/kg). Pulmonary artery
      and peak airway pressures were significantly lower and compliance higher in
      groups III and IV lungs after 3 hours of reperfusion (p < 0.05) compared with
      group I. Group I and III lungs had significantly less edema than group II (p <
      0.05). The arterial partial pressure of oxygen was similar in all stored groups
      (II to IV).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7818363
TI  - Optimizing "delay period" for burst stimulation in dynamic cardiomyoplasty.
AB  - Hemodynamic evidence of systolic assist after dynamic cardiomyoplasty remains
      inconsistent. One of the relevant factors may be how the burst stimulator is
      programmed. In 3 patients who underwent cardiomyoplasty for idiopathic dilated
      cardiomyopathy, we examined the modes used to determine the delay period between
      the R-wave sensing and the onset of burst stimulation during cardiac systole.
      These modes include the fixed time mode, the valve-synchronized mode, and the
      flow-optimized mode. The rationale for choosing these modes and the benefits
      conferred by each are discussed.

PMID- 7818364
TI  - Carcinoid tumors of the lung: do atypical features require aggressive management?
AB  - Atypical carcinoids are an intermediate form of tumor between low-grade malignant
      typical carcinoid and high-grade malignant small cell carcinoma, which represent
      the two ends of the spectrum of neuroendocrine bronchopulmonary tumors. Between
      1983 and 1993, 27 patients with atypical carcinoids underwent surgical treatment.
      The histologic diagnosis of an atypical carcinoid was established if the criteria
      proposed by Arrigoni and associates were fulfilled. Seven pneumonectomies, 16
      lobectomies, 2 segmentectomies, and 2 wedge resections were performed. Thirteen
      patients (48.1%) had regional nodal metastases and 6 patients (22%) had N2
      disease at the time of surgical therapy. Distant metastases developed in 5
      patients (18.5%) after initial treatment. The 10-year survival in patients with
      an atypical carcinoid was 49%, versus the 84% 10-year survival rate observed in
      patients with a typical carcinoid. We conclude that the aggressive behavior of
      atypical carcinoids precludes the use of limited surgical resection and requires
      a more aggressive approach, with lobectomy and mediastinal lymph node dissection
      constituting a minimal procedure. The same criteria used for well-differentiated
      lung carcinoma should apply to this form of neuroendocrine lung tumor. Adjuvant
      chemotherapy is recommended for patients with stage III or distant metastases.

PMID- 7818365
TI  - Stroke during coronary artery bypass grafting using hypothermic versus
      normothermic perfusion.
AB  - Does the abandonment of hypothermic perfusion during cardiopulmonary bypass
      compromise cerebral protection and thus lead to a higher incidence of stroke?
      From 1987 to June 1993, 2,585 consecutive patients underwent myocardial
      revascularization using warm-body (perfusion at 37 degrees C), cold-heart (cold
      cardioplegic arrest) surgical technique and were followed for new overt
      neurologic deficits. Perfusion pressure was maintained between 50 and 70 mm Hg,
      and hematocrit was kept around 20%. There were 25 operative deaths (1%) in this
      normothermic group, and new neurologic deficits developed after operation in 25
      patients (1%). These results were compared retrospectively with those in 1,605
      patients who underwent myocardial revascularization between 1980 and 1986 with
      moderate hypothermic (25 degrees to 30 degrees C) perfusion, the same surgical
      team, and similar operative techniques. The normothermic group included more
      elderly patients, more patients with left ventricular dysfunction and unstable
      angina, and more frequent use of an internal mammary artery conduit. Neurologic
      complication rates were 1% and 1.3% for the normothermic and hypothermic
      perfusion groups, respectively. Risk factors for stroke that were identified
      included age greater than 70 years, severity of aortic arch atherosclerosis, and
      severe hypotension in the perioperative period. Thus, in a large clinical series,
      the incidence of overt neurologic injuries was found to be no higher with
      normothermic perfusion than with hypothermic perfusion.

PMID- 7818366
TI  - Acute traumatic rupture of the aortic isthmus: repair with cardiopulmonary
      bypass.
AB  - In an attempt to prevent paraplegia, a devastating complication common after the
      repair of traumatic rupture of the aorta, we have used partial cardiopulmonary
      bypass. Most of the patients in our series (79.5%) underwent other major surgical
      procedures immediately before or after the aortic repair. Eight of the 110
      patients died before aortic repair could be performed. The aorta was not repaired
      in 3, because of other injuries. In 9, the repair was done without a shunt or
      bypass; 4 patients died and 2 (22.2%) survived without paraplegia. One of the 2
      who underwent repair with a Gott shunt died; the survivor suffered no cord
      damage. Of the 88 patients whose repair was carried out under cardiopulmonary
      bypass, 6 died and 80 (90.9%) survived without paraplegia. None of the last 39
      patients has become paraplegic, as vasodilator treatment is now discontinued
      during the cross-clamp period. Serious intracranial injury was present in 19
      patients; in 3 (15.8%) the injury became worse after repair. There was no
      evidence of new or increased intraabdominal bleeding during heparinization.
      Except in the event of pulmonary lacerations, systemic heparin therapy was not
      associated with major problems.

PMID- 7818367
TI  - Observations in infertile African males at an andrology clinic in South Africa.
AB  - The major cause of infertility among black Africans is traditionally attributed
      to a female factor and few reports are available on the male factor. This study
      analyzed the clinical and seminal data obtained from a population of 1726
      suspected infertile African men evaluated from July 1985 to June 1991. The
      possible cause of infertility was judged on the results of first semen analysis.
      Of these men, 49% were secondarily infertile and 36% had previously received
      treatment for a urethral discharge. Varicocoeles were present in 183 cases (11%)
      and 11% had serological evidence of previous exposure to syphilis. Azoospermia
      was present in 152 patients (9%), 5% had polizoospermia, 45% had hypospermia (< 2
      mL) and 9% (> 6 mL) had hyperspermia. In 70% of patients a possible contributing
      male factor for infertility was found. It would appear that the male factor
      contributed significantly to infertility, and evaluation of the black African
      male can therefore be regarded as a rewarding venture.

PMID- 7818368
TI  - Hormone profiles and testicular histology in cryptorchid boys with marker
      chromosome.
AB  - Hormone profiles and testicular histology were studied in two cryptorchid boys
      with marker chromosome. Plasma testosterone levels were abnormally low in both
      cases. Plasma levels of gonadotropins and prolactin were within normal ranges in
      case 1, but case 2 showed decreased concentration of plasma gonadotropins and
      normal level of plasma prolactin. The administration of LH-RH induced low
      response of plasma gonadotropins in case 1 and exaggerated response in case 2.
      The response of plasma testosterone to the administration of hCG was poor in both
      cases. Testicular histology showed maturation arrest and reduction of tubular
      diameter and Leydig cells per seminiferous tubules in both cases. Although
      testicular histology in these cases were similar to those in prepubertal or
      pubertal boys with cryptorchidism, hormonal disturbances were more severe. It
      would appear that marker chromosome enhances hormonal alterations.

PMID- 7818369
TI  - Effect of low-dose prednisolone on sperm fertilizing capacity in subfertile men
      with circulating antisperm antibodies.
AB  - To assess if low-dose prednisolone reduced circulating antisperm antibodies and
      improved sperm fertilizing capacity, the hamster oocyte penetration test (HOPT)
      was used to evaluate treatment in 36 males with significant serum antisperm
      antibodies, measured by the tray agglutination test (TAT). Prednisolone 5 mg
      three times a day for 3 months was used. Only couples in whom all tests in the
      female partner were normal were entered into the study. A significant increase in
      sperm density, normal morphology, and HOPT were noted after therapy (p < .001). A
      significant decrease in antisperm antibody titer was noted (p < .0001) and
      correlated with improvement of HOPT (p < .05). There were no significant side
      effects. Six pregnancies (17%) occurred. Three pregnancies (18%) occurred in
      partners of an untreated group of 17 men. Prednisolone therapy in this regime
      does not significantly improve pregnancy rates. The HOPT does not offer any
      additional information for predicting patients who will show an improvement in
      antibody titers or achieve pregnancy after steroids.

PMID- 7818370
TI  - Human testis vitamin D binding protein involved in infertility.
AB  - Immunoglobulin G (IgG) fraction was prepared from a serum obtained from an
      infertile woman containing antisperm antibodies that induced head-to-head
      agglutination of human sperm. The antibodies in the IgG fraction interacted with
      a 60-kD protein found in human testes determined by Western blot. The 60-kD
      protein was purified from human testis by isoelectric focusing (IEF), affinity
      chromatography on blue sepharose column, and preparative electrophoresis with
      electroelution. The purified 60-kD protein migrated as a single homogeneous band
      when analyzed by SDS-PAGE. The amino acid sequence of the N-terminus was
      determined. The initial 10 amino acid residues were identical to the human serum
      vitamin D binding protein (VDBP). Polyclonal antibodies were raised against the
      60-kD protein. The polyclonal anti-60-kD antibodies and the anti-VDBP antibodies
      obtained from a commercial source immobilized human sperm in vitro. The
      interacting antigens were located on the postacrosomal region and midpiece of
      human sperm, as determined by an immunofluorescence method. The IgG fraction
      prepared from the serum of an infertile woman interacted with the human testis 60
      kD protein but failed to stain serum VDBP. The results suggest that the 60-kD and
      VDBP are related proteins but not identical entities and that the 60-kD protein
      contains a unique structural group lacking in serum VDBP. Production of
      antibodies against the unique structure of the 60-kD protein may be the cause of
      the infertility.

PMID- 7818371
TI  - Antibodies to human seminal plasma inhibin adversely affect sperm function
      parameters.
AB  - Polyclonal antibodies to intact inhibin (94 amino acids, R-94, 10.5 kDa) and its
      sequence specific synthetic fragments (R-9, R-17) were evaluated for their effect
      on various physical and biochemical parameters of sperm function. Intact inhibit
      had maximum deleterious effect on quantitative motility and mean forward
      progression of spermatozoa. Antibodies had no effect on sperm fructolysis and
      sperm nuclear chromatin decondensation reaction. Sperm plasma membrane was
      damaged in antibodies treated spermatozoa as evidenced by hypoosmotic swelling
      test and sperm lipid peroxidation reaction.

PMID- 7818372
TI  - Failure of test yolk buffer to decrease antisperm antibodies on sperm.
AB  - The objective of this study was to evaluate whether the suspension of sperm
      naturally bound or artificially coated with antisperm antibody (ASA) in test yolk
      buffer (TYB) will reduce the percentage of sperm positive for ASA. Attempts were
      made to repeat a study performed by Lam et al., in which they claimed a
      significant decrease in percentage of sperm positive for both IgA and IgG.
      Furthermore, the study attempted to determine if this methodology would similarly
      reduce the percentage of sperm naturally bound with ASA. There was no reduction
      in postincubation levels in percentage of sperm having attachment of IgA or IgG
      in either the sperm specimens naturally bound with ASA or donor sperm
      artificially coated with antibodies. Incubation in TYB does not appear to be an
      effective method to reduce the percentage of sperm bound with ASA. Possibly, it
      could reduce the amount of ASA bound to each sperm, but this would have to be
      proven by other studies.

PMID- 7818373
TI  - Penetration capacity of spermatozoa from patients with
      oligoasthenoteratozoospermia into bovine cervical mucus before and after therapy
      with kallikrein.
AB  - Due to the high degree of subjectivity involved in quantifying sperm motility by
      light microscopy, it appeared of interest to compare the results obtained with a
      bovine mucus penetration test (Penetrak) to those of routine laboratory
      measurement before and after therapy with kallikrein (600 U/day). The study
      included 45 patients with oligoasthenoteratozoospermia (OAT syndrome) in the
      absence of genitourinary pathology or abnormal serum hormone levels. Infertile
      partnership has lasted for a mean of 3.2 years. Analysis of spermiograms and the
      penetration test were performed before and after 3 months of treatment. Neither
      of these techniques revealed significant alteration after treatment, nor was
      there a demonstrable success during the observation period in terms of pregnancy.
      Judging from these results, (1) kallikrein has no effect in patients with OAT
      syndrome and (2) the penetration test provides no additional information on the
      biological quality of ejaculate.

PMID- 7818374
TI  - Modified resazurin reduction test for determining the fertility potential of
      bovine spermatozoa.
AB  - The objective of this study was to determine if reduction of the dye resazurin by
      bovine sperm is associated with the concentration of motile and progressively
      motile sperm. Metabolically active sperm reduce resazurin (blue color) to
      resorufin (pink color) and upon further reduction to dihydroresorufin (white
      color). A total of 68 semen samples from 20 Limousin bulls were collected using
      electroejaculation. The concentration of motile and progressively motile sperm
      was determined. Resazurin was added to each semen sample (8.8 microgram/mL
      semen), samples were then incubated at 37 degrees C for a maximum of 15 min, and
      visual color changes indicative of dye reduction were noted. Samples were
      identified as having either low fertility potential (< 200 x 10(6)/mL motile
      sperm and < 100 x 10(6)/mL progressively motile sperm) or high fertility
      potential (> or = 200 x 10(6)/mL motile sperm and > or = 100 x 10(6)/mL
      progressively motile sperm). Assessment of the reduction of resazurin from blue
      to pink (< or = 3.5 min) allowed identification of 88% of the low and 94% of the
      high fertility potential samples. In addition, the reduction of resazurin from
      blue to white (< 15 min) resulted in identification of 82% of the low and 76% of
      the high fertility potential samples. The modified resazurin reduction test is
      useful for determining the fertility potential of bovine spermatozoa.

PMID- 7818375
TI  - Localization of wheat germ agglutinin lectin receptors on human sperm by
      fluorescence microscopy: utilization of different fixatives.
AB  - Wheat germ agglutinin (WGA) and Concanavalin A (Con A) seem to be the most widely
      studied of the lectins used to investigate sperm surface receptors. It has been
      reported that WGA receptors on human sperm membranes may be closely related to
      male fertility and that WGA receptor deficiency may cause human infertility.
      Although these claims may not be negated, there are many discrepancies in current
      literature regarding the localization and detection of human sperm WGA receptors.
      These discrepancies are probably the result of variations in the pretreatment of
      sperm before fixation and sperm-lectin interaction. This study investigated the
      effect of different fixation procedures on the localization of human sperm WGA
      receptors on normal spermatozoa. Comparative studies were performed on
      spermatozoa separated by wash-swim-up and fixed with 4% formaldehyde, 95%
      ethanol, or Bouin's solution, or nonfixed (air-dried) using fluorescein
      isothiocyanate-conjugated WGA. There were significant differences (p < .01) in
      the % WGA receptor localization following the different fixation procedures on
      samples receiving the same treatment previous to fixation. The different
      fixatives affect the plasma membrane to different degrees, resulting in an
      alteration of lectin receptor localization. To allow a better comparison and
      understanding of results, a standardized preparation procedure is recommended
      during studies using lectins as molecular probes. The results suggest than an
      aldehyde fixative may be the fixative of choice for sperm membrane studies.

PMID- 7818376
TI  - Presence and chemical composition of glycoproteic layer on human spermatozoa.
AB  - Studies from electronic microscopy disclosed the presence of an electrodense
      stranded and branch-like electrodense layer that extends toward extracellular
      space. Chemical composition of this glycoproteic layer showed that protein and
      total sugar content is similar (0.98 microgram/microgram protein). As for the
      total sugar content of this glycoproteic constituent, sialic acid accounts for
      40%, hexosamines 27%, and fucose 30%. Electrophoresis characterization of this
      constituent showed the presence of 6 different motility bands. Risen levels of
      sialic acid indicate the contribution of sialic residue in the net charge of the
      sperm membrane, its role during capacitation, and its possible participation in
      the formation of binding bridges between sperm membrane and ovum.

PMID- 7818377
TI  - Computer-aided semen analysis variables as predictors of male fertility
      potential.
AB  - A computer-aided semen analysis (CASA) was used to allow digitizing the motion of
      the spermatozoon. This procedure allows an objective means of judging semen
      quality, especially the translational movements of spermatozoa. Forty-three
      couples were included in the study. The average age of the male was 35.5 +/- 4.7
      years and that of the female was 32.7 +/- 4.7 years. The average duration of
      infertility was 3.8 +/- 2.3 years. Using multiple linear regression analysis of
      26 prognostic variables, a cluster of 8 variables significantly predicted
      pregnancy maximally. The 8 variables and the resultant multiple correlation
      coefficients were used to generate a multiple regression equation which allowed
      the correct separation of the population into fertile and infertile couples. The
      mean pregnancy predictor values of the fertile and infertile populations were
      significantly different using the analysis of variance.

PMID- 7818378
TI  - Multifrequency tympanometry. Preliminary experiences with a commercially
      available middle-ear analyzer.
AB  - Normal ears and ears affected by various pathologies were studied with a clinical
      middle-ear analyzer according to the multifrequency tympanometric concept, by
      which the resonance frequency of the tympanic membrane/middle-ear system can be
      determined. This frequency varies considerably in normal ears with a mean value
      close to 1 kHz. Ears with pathologies in the tympanic membrane and otosclerotic
      ears have resonance frequencies differing significantly from those of normal
      ears. The effects may be explained by considering mass and stiffness components.

PMID- 7818379
TI  - Reproducibility of the electric response components in clinical
      electrocochleography.
AB  - The reproducibility of transtympanic electrocochleographic components was
      investigated in normal-hearing subjects and in patients with Meniere's disease.
      The electric responses to short clicks and long tone bursts were studied using
      repeated stimuli within the same test (intratest), and after replacement of all
      electrodes (intertest). The parameters of the response to clicks, such as the
      SP/AP (summating potential/action potential) ratio and the width of the complex
      as well as the amplitudes of the response to clicks presented at fast repetition
      rate, were analyzed. Absolute amplitudes of the SP were measured using long tone
      bursts of 4, 2 and 1 kHz. It was found that the intratest reproducibility of the
      responses was good for all the parameters. The intertest responses showed a
      larger variability, particularly when long bursts were used. Parameters obtained
      from hydroptic ears, which could be considered mainly representative for the SP,
      showed the largest variability of the responses. The effect of replacement of the
      electrodes amounted to less than 35% of the total intertest variability which
      would indicate that replacement of the electrodes did not significantly influence
      the recordings obtained at different measurement occasions in the same patient.
      The upper normal limit value indicating changes which could be contributed to
      biological fluctuations and the method of measurements were calculated for each
      response parameter. Changes exceeding these values could thus be attributed to a
      real change in the electric cochlear potentials, at the 95% confidence level.

PMID- 7818380
TI  - Effects of click polarity on the binaural interaction components of human
      auditory brainstem-evoked potentials: a three-channel Lissajous trajectory study.
AB  - Three-channel Lissajous trajectories (3-CLTs) of the binaural interaction
      components of the auditory brainstem-evoked potentials were recorded from 17
      adult subjects in response to rarefaction, condensation and alternating polarity
      clicks. All 3-CLTs included 3 planar segments (named Bd, Be and Bf) whose
      latencies, amplitudes, orientations, sizes and shapes were not affected by click
      polarity. A significant increase was found in the duration of planar segment Be
      to alternating polarity clicks. This effect may be explained by limitations of
      spatiotemporal resolution of the method, which did not allow distinction of
      contributions from temporally overlapping generators participating in binaural
      processing.

PMID- 7818381
TI  - Effect of natural sleep on auditory steady state responses in adult subjects with
      normal hearing.
AB  - Auditory 40-Hz steady state response (SSR), auditory brainstem response (ABR),
      and middle-latency response (MLR) were recorded in 12 healthy adult females with
      normal hearing while awake and asleep. The responses were recorded with 500-Hz
      tone pips at 55 dBnHL. Synthesized SSR were made by superimposing the recorded
      ABR and MLR waveforms (ABR-MLR), and their amplitudes were compared with those of
      the actually recorded SSR. In the waking state, the ratio of the mean amplitude
      of recorded SSR to that of synthesized SSR was 0.819, whereas in the sleeping
      state it decreased to 0.522, a statistically significant difference. The results
      indicate that the SSR can be predicted from the linear superimposition of ABR and
      MLR in the waking state, but not in the sleeping state.

PMID- 7818382
TI  - Effect of time scale modification of speech on the speech recognition threshold
      in noise for elderly listeners.
AB  - The effect of time scale modification of speech on the speech recognition
      threshold in noise (SRTN) was investigated for a group of 44 elderly subjects,
      varying in age from 56 to 88 years with sloping mild-to-moderate sensorineural
      hearing losses. Subjects' pure-tone average thresholds at 500, 1,000 and 2,000 Hz
      (PTA1) ranged from 3 to 58 dB. The study confirms the well-known fact that speech
      recognition in noise deteriorates with increasing age. Furthermore, time
      compressing speech results in an even greater influence of age on the SRTN. The
      apparent age effect on SRTN values referenced to SRTN in the control condition is
      mostly caused indirectly by the significant correlation between age and PTA1,
      although there was a slight tendency for age to have a greater independent effect
      on relative SRTN values when the amount of time compression increased. The
      percentage of explained variance in relative SRTN values by the subject variables
      in this study was limited, indicating that there are other factors not
      investigated in this study (e.g. cochlear mechanisms, short-term memory, feature
      extractors) that significantly influence the effect of time compression on SRTN.

PMID- 7818383
TI  - Auditory perceptual and visual-spatial characteristics of gaze-evoked tinnitus.
AB  - Auditory perceptual and visual-spatial characteristics of subjective tinnitus
      evoked by eye gaze were studied in two adult human subjects. This uncommon form
      of tinnitus occurred approximately 4-6 weeks following neurosurgery for gross
      total excision of space-occupying lesions of the cerebellopontine angle and
      hearing was lost in the operated ear. In both cases, the gaze-evoked tinnitus was
      characterized as being tonal in nature, with pitch and loudness percepts
      remaining constant as long as the same horizontal or vertical eye directions were
      maintained. Tinnitus was absent when the eyes were in a neutral head-referenced
      position with subjects looking straight ahead. The results and implications of
      ophthalmological, standard and modified visual-field assessment, pure-tone
      audiometric assessment, spontaneous otoacoustic emission testing and detailed
      psychophysical assessment of pitch and loudness are discussed.

PMID- 7818384
TI  - Children's health: a crucial issue.

PMID- 7818385
TI  - Infant development and management of infant problems in a family setting.
AB  - Parental presentation of concerns about their infant in the first six months
      often involve feeding or sleeping patterns. These concerns may arise from
      difficulties in an individual parent's own development, or from problems in the
      marital relationship.

PMID- 7818386
TI  - The first six months. So easy to miss....
AB  - Most presentations to general practitioners in the first six months of life are
      for common childhood conditions. These include upper respiratory tract
      infections, infectious gastroenteritis, other viral illness associated with
      fever, feeding difficulties, management of sleep disturbances, constipation and
      routine immunisation. Rarely, more sinister disorders may be present and
      differentiating them from the common benign problems represents a constant
      clinical challenge.

PMID- 7818387
TI  - The abused child. Recognising common patterns of non accidental injury.

PMID- 7818388
TI  - Feeding difficulties. Part 1. Breast feeding.
AB  - Breast feeding is a learned process and often poses difficulties for new mothers.
      Time spent managing breast feeding difficulties with accurate advice and a
      compassionate ear will be rewarded with a greater percentage of infants in our
      community being fed the most appropriate milk for them.

PMID- 7818389
TI  - Feeding difficulties. Part 2. Artificial feeding.
AB  - It is vital that GPs resist the temptation to change the type of formula being
      fed to an infant without a clear indication. In addition to the confusion it
      creates for mothers and infants, it is potentially hazardous.

PMID- 7818390
TI  - Vomiting and diarrhoea.
AB  - Diarrhoea and vomiting are common symptoms in infants up to six months of age.
      While the symptoms often reflect a gastrointestinal disorder the attending
      physician needs to be aware of possible non gastrointestinal causes. Such
      symptoms occurring in the newborn often point to congenital causes. Dehydration
      and nutrition are the key points needing attention in the management of diarrhoea
      in infants. Drugs virtually have no role in the management of diarrhoea and
      vomiting in infants.

PMID- 7818391
TI  - Interpractice visits by general practitioners.
AB  - Most of the objectives have thus been successfully met as the interpractice
      visits have proven to be a well accepted form of self-regulated implicit peer
      review activity among GPs, continuing with enthusiasm on the part of the
      participants over a period of five years and now propagating nationally.
      Significant to the success is the ownership of the scheme by the participants.
      The advent of QA and CE credit points can only enhance participation rates.
      Continuing attention to the principles of audit, namely evaluation, change and
      review, will refine the method in the future into an even more effective tool,
      which can be recommended to all those in general practice. A necessary area for
      attention in the future is effective outcome evaluation.

PMID- 7818392
TI  - Continuing medical education needs for local general practitioners.
AB  - A survey was conducted of the expressed continuing medical education needs of a
      group of 64 suburban general practitioners attached to a South Australian
      Hospital. The top five stated urgent and necessary training needs were acute and
      emergency disease management, diabetes management, terminal care, dermatology and
      medicine. The form of CME most preferred was patient/clinical practice and the
      greatest barriers to CME were stated as lack of time and loss of income.
      Practitioners with less than 10 years experience significantly chose training in
      ear, nose and throat (p < 0.01), rheumatology (p < 0.01) (Fisher's exact test,
      two-sided), compared with more experienced practitioners. Those in group practice
      significantly chose training in orthopaedics (p < 0.01, Fisher's exact test, two
      sided) and the management of change (p = 0.037, Fisher's exact test, one-sided)
      more than solo practitioners while female practitioners significantly expressed
      the need for ante natal care training (Chi square = 8.85; df = 1; p < 0.01).

PMID- 7818393
TI  - Assessment of general practitioners' management of hyperlipidaemia. A study using
      personal visits and a scenario-based questionnaire.
AB  - In summary our study has looked at the current management practices of
      hyperlipidaemia by general practitioners in an innovative way. Our results
      suggest that most GPs are managing this condition appropriately. Where their
      management differs from current guidelines is mainly in introducing medication
      early. We obtained significantly lower participation rates in the metropolitan as
      compared with the regional and rural areas, but we found no significant
      differences in the overall assessment of appropriate management between the
      different geographical regions of Victoria.

PMID- 7818394
TI  - Antibiotic trends in the veteran community.
AB  - The Department of Veterans' Affairs has recently developed improved computer
      software that enables more thorough analysis of the prescription data in the
      pharmaceutical database. The department is now in a position to follow
      prescribing trends in detail for all drugs prescribed for the veteran population.
      Several drug groups are of interest and on this occasion we have elected to
      examine the commonly prescribed antibiotics.

PMID- 7818395
TI  - Postural hypotension and the anti-gravity suit.
AB  - An air force anti-gravity suit, as used by fighter pilots to prevent loss of
      consciousness, has been successfully employed to treat severe postural
      hypotension in a patient with Shy-Drager syndrome. The definition of postural
      hypotension is reviewed, and reference is made to the previous use of the anti
      gravity suit in the treatment of this condition.

PMID- 7818396
TI  - Epilepsy in my life.
AB  - The author presents a personal account of his battle with the problem of complex
      partial seizures (temporal lobe epilepsy). This exposure and knowledge obtained
      from the tales of colleagues in a support group convinced him that the emotional
      side of epilepsy is not properly understood.

PMID- 7818397
TI  - Postmenopausal osteoporosis.

PMID- 7818398
TI  - Corticosteroid-induced osteoporosis.

PMID- 7818399
TI  - Male osteoporosis.

PMID- 7818401
TI  - Neurology quiz. Patent foramen ovale.

PMID- 7818400
TI  - The management of osteoarthritis in general practice. Results from the Australian
      Morbidity and Treatment Survey, 1990-1991.
AB  - Osteoarthritis is the fourth most commonly managed problem in general practice in
      Australia. This paper provides an overview of its management in general practice.

PMID- 7818402
TI  - Office biochemistry.

PMID- 7818403
TI  - Patient education. The infertile couple.

PMID- 7818404
TI  - Polypathology over time.
AB  - This case study traces the management of a woman presenting at the age of 55 with
      isolated systolic hypertension and records her history for 24 years--from
      apparent good health to death. A series of events and the patient's and the
      doctor's reactions to them are described.

PMID- 7818405
TI  - Simple gifts.

PMID- 7818406
TI  - Health assessment for commercial driving. The general practitioners' role.
AB  - Death and injury rates associated with commercial vehicle driving are
      unacceptably high. Pre-existing medical conditions may contribute to road
      accidents and the National Road Transport Commission (NRTC) has developed a set
      of uniform guidelines, based on best available evidence, which might preclude at
      risk individuals from holding commercial licences. Standardised clinical
      examinations performed by general practitioners (GPs) will be used to assist
      regulatory authorities in their licensing procedures. This article sets out the
      process of development of the guidelines as well as the construction and use of a
      medical assessment form to be used by GPs in facilitating the licensing process
      in each State.

PMID- 7818407
TI  - A case of dementia.
AB  - Recognition of cognitive impairment in the elderly is an important part of
      medical care. This will lead to the proper diagnosis and optimum treatment.
      Families seldom realise that the patient has dementia. Even with a high index of
      suspicion, the diagnosis can often be missed. The correct tool for making the
      diagnosis is also controversial.

PMID- 7818408
TI  - Practice tip. Wedge resection of axillary sweat glands.

PMID- 7818409
TI  - CT scanning and headaches.

PMID- 7818410
TI  - Boutique versus supermarket general practice. What should we teach?

PMID- 7818411
TI  - Digby Ian Harris. Over 40 years of devotion to rural practice.

PMID- 7818412
TI  - Ensuring the safety of therapeutic devices.

PMID- 7818413
TI  - Rural practice training in SA.

PMID- 7818414
TI  - Salmeterol in the treatment of asthma.

PMID- 7818416
TI  - Autologous blood donation in total hip replacement.
AB  - The effectiveness of autologous blood donation in reducing the need for
      homologous transfusion was evaluated in a review of 529 consecutive total hip
      replacements (THR) from 1988 to 1992. The review was retrospective from 1988 to
      1990 and prospective from 1991 to 1992. Since 1988 there have been 188 primary
      THR performed using autologous blood donation. In 1988-89, this represented 18%
      of all primary THR, in 1990 37% and in 1991-92 73%. This increase reflects a
      growing enthusiasm for the programme and a loosening of age restrictions. In 1991
      92, 4% of autologous donors undergoing primary THR required homologous
      transfusions compared to 84% of non-autologous donors. Over the same period after
      revision THR, 36% of autologous donors required homologous transfusions compared
      to 100% of non-autologous donors. The participation rate of patients undergoing
      revision THR was 33%. The prospective part of the study in 1991-92 compared
      autologous and matched non-autologous patients. Blood loss, transfusion volumes
      and operating time were identical. The pre- and postoperative haemoglobin
      concentrations in the autologous group were lower by 15 and 10 g/L, respectively,
      after primary THR and by 10 g/L in both instances after revision THR. This was
      not reflected in a longer admission.

PMID- 7818417
TI  - Surgery for the morbidly obese patient.

PMID- 7818415
TI  - Oesophageal cancer: outcome of modern surgical management.
AB  - Many clinicians still associate oesophagectomy for oesophageal carcinoma with low
      cure rates, poor palliation and prohibitive peri-operative mortality. Surgical
      advances have rendered such perceptions inaccurate. A prospective study of all
      patients undergoing surgery for oesophageal cancer in an Australian teaching
      hospital between 1979 and 1993 has been undertaken. Selection, staging, pre
      operative preparation, surgical technique and postoperative care were all
      carefully controlled. One hundred and thirty-seven patients were explored. Twenty
      one were inoperable. One hundred and sixteen underwent resection with intent to
      cure. Hospital mortality for oesophagectomy was 1.7%. There were no cases of
      clinical anastomotic leakage. Eighty-nine per cent achieved excellent to good
      swallowing. The median survival for all cases was 14 months and the 5 year
      survival was 18%. Median survival for resected cases was 18 months and the 5 year
      survival was 26%. The long-term survival was related to postoperative stage of
      the disease but not to tumour type. Oesophagectomy for oesophageal cancer will
      restore good swallowing in 90% of cases. Operative mortality should be less than
      5% and the overall 5 year survival 20-30%. Early tumours can often be cured (ca
      in situ 100%, stages I and II 50-60%), indicating the benefits of early
      detection. Poor survival in advanced disease (stage III 15%, stage IV 0%) on a
      background of low surgical mortality indicate the need for better staging and
      more effective adjuvant therapies.

PMID- 7818418
TI  - Microsurgical vasovasostomy in military personnel.
AB  - This paper details the operative techniques, results and reasons for reversals of
      vasectomy in military personnel. Fifty-two reversals were performed by two
      surgeons (AC & DW) over a 7 year period. Data collection was by (i) retrospective
      analysis of service documents, surgical registers and laboratory records and (ii)
      response to a questionnaire. The interval between original vasectomy and reversal
      varied from 5 months to 16 years. Change of sexual partner was the most common
      reason for requesting the procedure. There were two recorded postoperative
      infections and no postoperative mortality. Post-reversal semen analysis proved
      anastomotic success in 49 out of 51 cases (96%). Semen analysis was not returned
      for the remaining case. Of the couples who had been trying for at least 18
      months, 28 out of 42 (67%) had conceived, including one miscarriage. A further
      seven cases had been trying for less than 18 months, or had no opportunity due to
      physical separation. Two of these seven patients ended their relationship soon
      after operation. Pregnancy outcome was unknown in three cases.

PMID- 7818419
TI  - Renal allograft survival in patients with congenital obstruction of the posterior
      urethra.
AB  - In an attempt to clarify the influence of dysfunctional bladders on renal
      allograft outcome, graft survival was studied retrospectively in patients with
      congenital posterior urethral obstruction (posterior urethral valves). Using the
      Australia and New Zealand Dialysis and Transplant Registry (ANZDATA), 25 index
      patients were compared to all other transplant recipients of the same age range.
      Three instances of abnormal bladder function leading to graft function
      deterioration were found, therefore we would recommend investigation of bladder
      function in all boys with congenital urethral obstruction prior to renal
      transplant, and as part of the work-up of graft failure, where the cause is
      otherwise not obvious.

PMID- 7818420
TI  - Changing trends in urology practice: increasing outpatient surgery.
AB  - This study was performed to assess the changes occurring in the field of urology
      with developments in outpatient surgery during a 5 year period. Using ICD-9-CM
      code, data for all urology procedures performed in the main operating rooms, day
      surgery and laser centre operating rooms of a large, general hospital were
      collected for the years 1987-92. A substitution index (SI) was determined as the
      ratio of the number of outpatients to the total number of procedures and
      expressed as a percentage. Changes in the SI reflects the degree to which
      emphasis has shifted from conventional inpatient to outpatient surgery. It was
      found that 26% of urology procedures were being performed as outpatients in 1987,
      and this increased to 42% by 1992. When broken down according to organ, the
      greatest increase in SI from 1987 to 1992 was for the kidney (57%) and the least,
      the penis (2%), with ureter, urethra, testes and scrotum all revealing
      intermediate, but significant, increases (27, 28 and 24% respectively). This
      paper thus demonstrates that, as in other fields, urology has experienced a
      marked increase in outpatient surgery. With developments in surgical and
      anaesthetic techniques, financial pressures, changing physician and patient
      attitudes and technological advances, further increases in urology outpatient
      care can be expected.

PMID- 7818421
TI  - Vertical banded gastroplasty for morbid obesity: weight loss at short and long
      term follow up.
AB  - A standardized vertical banded gastroplasty (VBG) was carried out by the one
      surgeon on 60 consecutive morbidly obese patients. All patients were followed at
      4 week intervals for 1.5 years. Long-term follow up was carried out at medians
      5.7 and 9.6 years. All patients had significant weight loss at 1.5 years.
      However, at long-term follow up, despite an apparently intact gastric restrictive
      procedure, only 40% of patients had maintained their weight loss. Sixty per cent
      had regained significant weight and 31% had returned to or were above their pre
      operative weight level.

PMID- 7818422
TI  - Colonoscopy: how far is enough?
AB  - Total colonoscopy is arguably the best method available for examination of the
      colon and rectum. Colonoscopy costs are high and rising and it may be that in the
      future practitioners will be unable to afford to colonoscope all of the patients
      presently being examined. This retrospective study was undertaken in an attempt
      to examine the cost, in terms of lesions missed, of a limited endoscopy
      programme. During a 15 year period, 1426 colonoscopies were performed at
      Wellington Hospital, New Zealand. Total colonoscopy was possible in 79% of all
      patients. Three perforations occurred. Nine patients bled and two required blood
      transfusion after biopsy or 'snaring' of polyps. After exclusion of patients with
      continuous inflammatory bowel disease (IBD) 75% of all lesions were found in or
      distal to the descending colon. More cancers were found in patients colonoscoped
      because of bleeding. Thirty-two of 93 cancers diagnosed were proximal to the
      descending colon but 18 presented with bleeding. A further seven had a
      radiological abnormality. Only 7.5% of colorectal cancers would be missed by
      flexible sigmoidoscopy (65 cm) and 75% of the costs of total colonoscopy would be
      avoided if only patients presenting with bleeding and IBD were offered total
      colonoscopy and patients with radiological abnormalities were treated according
      to the abnormality. This compromise, based on the data presented, may represent a
      rational way to reduce colonoscopy costs.

PMID- 7818423
TI  - Autonomic nerves cross the posterior plane of rectal dissection.
AB  - This investigation was an anatomical study to determine whether branches of the
      pre-sacral autonomic plexus cross the posterior plane of surgical dissection to
      supply the rectum. Initially four cadaver hemi-pelves were dissected. Twelve
      patients undergoing full rectal mobilization were then studied at operation. In
      all subjects the pre-sacral nerves were arranged as a plexus below the sacral
      promontory, rather than as individual left and right nerve trunks. Structures
      thought to be nerves were identified crossing the plane of posterior mobilization
      of the rectum. They were traced towards their origin and destination,
      photographed and representative fibres biopsied. A total of 42 such structures
      were biopsied (16 in cadavers, 26 in operative cases) and 40 were confirmed to be
      nerves. These nerves connect the pre-sacral autonomic plexus with the posterior
      aspect of the rectum and were found at all sacral levels. In the operative cases
      the level of the positive biopsies were S1-six, S2-six, S3-five, S4-four, S5
      three. The posterior plane of rectal dissection is therefore crossed by autonomic
      nerves that innervate the rectum. The pre-sacral nerves have been found to form a
      plexus in all subjects.

PMID- 7818424
TI  - The general versus regional anaesthesia debate: time to re-examine the goals.
AB  - New justification for the use of regional anaesthesia, either alone or in
      combination with general anaesthesia, has been provided with reports of some
      unexpected influences on outcome. A reduction in the incidence of postoperative
      thrombotic episodes and vascular graft occlusion is strongly suggested in
      patients with generalized vascular disease. Application of a variety of drugs,
      including local anaesthetics, opioids and adrenergic agonists, in the region of
      the spinal cord reduces afferent input during surgery and also the metabolic
      stress response. Evidence is increasing that this multi-modal approach to
      anaesthesia has important consequences in the spinal cord which result in
      modification of the postoperative requirement for analgesia. Premedication with
      opioid and other analgesics may also enhance this pre-emptive effect. New general
      anaesthetic and analgesic drugs are available that are more suited to these
      combined techniques. They have shorter duration of action so that plasma
      concentration can be rapidly adjusted to match a variable surgical stimulus.

PMID- 7818425
TI  - Treatment of childhood phimosis with topical steroid.

PMID- 7818426
TI  - Laparoscopic inguinal herniorrhaphy.

PMID- 7818427
TI  - Dorsal transscaphoid perilunate dislocation through an isolated scaphoid non
      union.
AB  - An unusual case of a traumatic dorsal transscaphoid perilunate dislocation
      occurring through an isolated scaphoid non-union is presented. This set of
      circumstances has not, to the authors' knowledge, been described previously.

PMID- 7818428
TI  - Metastasis-induced perforated appendicitis: an acute abdomen of rare aetiology.

PMID- 7818429
TI  - Carcinosarcoma of the ureter presenting as biliary colic.

PMID- 7818430
TI  - Paraduodenal hernia.
AB  - Over a 10 year period, four patients with paraduodenal hernia were encountered.
      Two had small hernias that were incidental findings at the time of surgery for an
      unrelated abdominal condition; these were managed by suture closure of the neck
      of the sac. The other two patients presented with intestinal obstruction and are
      discussed here with a review of the literature.

PMID- 7818431
TI  - Primary fibrosarcoma of the heart.
AB  - A case of primary fibrosarcoma of the heart, which was diagnosed in a 17 year old
      man, is presented. Extensive tumour resection and postoperative radiation therapy
      was carried out. The patient is alive after 18 months after the operation.
      Although these tumours are associated with very poor survival, early diagnosis
      and combined therapy may prolong life expectancy.

PMID- 7818432
TI  - Retroperitoneal malignant fibrous histiocytoma causing profuse bleeding per
      rectum.
AB  - A case is reported of retroperitoneal malignant fibrous histiocytoma (MFH)
      invading into the colon, causing fresh bleeding per rectum. It illustrates the
      difficulty encountered in the pre-operative diagnosis of this condition,
      especially in a patient with an atypical presentation of profuse lower
      gastrointestinal bleeding.

PMID- 7818433
TI  - Role of gastrografin study in the assessment of anastomotic leaks from cervical
      oesophagogastric anastomosis.
AB  - Gastric pull-up with cervical oesophagogastric anastomosis is a common procedure
      after oesophageal resection. Contrast studies are used by many surgeons for
      detection of anastomotic leaks but may be unnecessary. A prospective study was
      undertaken to compare gastrografin study and test feeding using water for
      detection of cervical anastomotic leaks. In 25 patients, gastrografin study
      showed three leaks, two of which were clinically silent and patients did not have
      any problems. One patient had aspiration of contrast and the study could not be
      completed. Two of the leaks detected clinically were missed by contrast study
      (one because of an incomplete study and the other was a satisfactory study).
      Delayed leaks occurred in two patients. All leaks healed spontaneously. A
      contrast study may thus be unnecessary for evaluation of a cervical
      oesophagogastric anastomosis and can be replaced with the simpler and safer
      technique of 'test feeding' using water.

PMID- 7818434
TI  - Effects of sodium monensin on reproductive performance of dairy cattle. I.
      Effects on conception rates, calving-to-conception intervals, calving-to-heat and
      milk production in dairy cows.
AB  - A total of 1061 lactating dairy cows in six different herds were randomly
      allocated to treatment and control groups. One herd was lot-fed on total mixed
      rations; three herds were fed on pasture with significant amounts of
      supplementary concentrates, and two herds were primarily pasture fed. Treated
      cows received a slow-release, intraruminal capsule containing 32 g sodium
      monensin within 7 days of calving. Conception rates at first service, days to
      first oestrus and calving-to-conception interval did not differ significantly
      between untreated and monensin-treated cows in the 5 herds, 3 herds and 4 herds,
      respectively, in which these outcomes were examined. Treatment of lactating cows
      immediately after calving may not be the optimal method to achieve fertility
      responses with capsules containing sodium monensin. Monensin treatment
      significantly increased milk yield in one of the six herds. Milk fat or milk
      protein production was not significantly affected by treatment.

PMID- 7818435
TI  - Effects of sodium monensin on reproductive performance of dairy cattle. II.
      Effects on metabolites in plasma, resumption of ovarian cyclicity and oestrus in
      lactating cows.
AB  - A randomised trial was conducted to determine the effects of sodium monensin on
      plasma metabolite concentrations, resumption of cyclicity and oestrus and milk
      production and milk composition of postparturient dairy cows. Cows treated with
      sodium monensin in a controlled-release capsule had significantly lower plasma
      beta-hydroxybutyrate (BHB) concentrations (P = 0.006) and tended (P = 0.07) to
      have significantly higher plasma glucose concentrations than untreated cows.
      Treatment did not significantly influence plasma free fatty acid, urea nitrogen
      or cholesterol concentrations. Despite higher plasma glucose concentrations and
      lower plasma BHB concentrations, periods from calving to first ovulation and
      oestrus were not reduced by treatment. This observation, with limited numbers of
      cows, is not consistent with a hypothesis that glucose or ketones are important
      metabolic regulators of pulsatile release of luteinising hormone and consequent
      resumption of cyclicity. While milk production and milk protein concentration did
      not significantly differ between groups, milk fat concentration was significantly
      lower for treated cows. Treated cows probably had lower dry matter intake than
      untreated cows as they produced 67 litres less milk per head and lost more weight
      than untreated cows during the study period, although weight and body condition
      score were not significantly affected by treatment. The lack of significance of
      these latter observations probably reflects the low statistical power of the
      study.

PMID- 7818436
TI  - The development of control methods for tick fevers of cattle in Australia.

PMID- 7818438
TI  - Effects of xylazine on humans: a review.

PMID- 7818437
TI  - A review of laboratory techniques and their use in the diagnosis of Leptospira
      interrogans serovar hardjo infection in cattle.
AB  - This paper reviews the laboratory diagnosis of Leptospira hardjo infection in
      cattle. Two genotypes of L hardjo, Hardjoprajitno and Hardjobovis, have been
      identified in cattle, but only Hardjobovis has been isolated in Australia. There
      are problems with diagnosis and control of bovine leptospirosis. Infection is
      usually subclinical and the serological titres vary greatly in peak and duration.
      Leptospires may be excreted in urine for up to 18 months. Low microscopic
      agglutination test titres may be significant in unvaccinated herds as indicators
      of endemic infection. Vaccines differ in their composition, and their efficacy is
      difficult to evaluate. The serological response after vaccination is difficult to
      differentiate from the response after infection. Pregnant cows that become
      infected may abort, but this is usually after the serological response has
      peaked. Therefore, paired serum samples are of little use in diagnosing abortion
      caused by L hardjo. Fluorescent antibody techniques are more sensitive than dark
      field microscopy for detection of leptospires in urine and tissue samples.
      Techniques for culture have improved but are still difficult to perform and take
      3 months or longer for results to be known. DNA probes and polymerase chain
      reaction tests are very sensitive and specific, quick to perform, and can be used
      on fluid and tissue samples.

PMID- 7818439
TI  - Haemangiosarcoma in the horse: three cases.

PMID- 7818440
TI  - Management of mycotic keratitis in a horse using a conjunctival pedicle graft.

PMID- 7818441
TI  - Giant cell enteritis in young crocodiles.

PMID- 7818442
TI  - A field case of ivermectin resistance in Ostertagia of sheep.

PMID- 7818443
TI  - The efficacy of a combination anthelmintic against oxibendazole resistant small
      strongyles, large strongyles and ascarids in horses.

PMID- 7818444
TI  - An evaluation of lectin agglutination and ampicillin sensitivity testing for the
      differentiation of Bordetella avium and the B avium-like organism.

PMID- 7818445
TI  - Natural infection of wild doves (Streptopelia senegalensis) with the virus of
      psittacine beak and feather disease.

PMID- 7818446
TI  - A diagnostic dilemma: detecting proliferative enteritis in pigs at slaughter.

PMID- 7818447
TI  - 11th Kendall Oration.

PMID- 7818448
TI  - Treatment of mild immersion hypothermia by forced-air warming.
AB  - Forced-air warming is used for prevention or reversal of hypothermia in surgical
      patients. In the present study, the efficacy of this system for treatment of
      immersion hypothermia was evaluated. Six men and two women were twice immersed in
      8 degrees C water until hypothermic. They were then rewarmed by either: 1)
      shivering-only inside a sleeping bag; or 2) forced-air warming. Esophageal and
      skin temperature, cutaneous heat flux and metabolism were measured. Afterdrop (+/
      SD) during forced-air warming (0.43 +/- 0.26 degrees C) was approximately 30%
      less than during shivering (0.61 +/- 0.26 degrees C) (p < 0.001). Rewarming rate
      during forced-air warming (3.26 +/- 1.8 degrees C.h-1) was not significantly
      different from shivering (3.02 +/- 1.2 degrees C.h-1). Skin temperature was
      higher during forced-air warming by 3.7 degrees C early and 4.5 degrees C after
      35 min of warming. Heat production increased by 77 W over the initial 20 min of
      shivering, and subsequently declined, compared to an immediate decrease with
      forced-air warming. During shivering heat flux ranged from 30 W early in
      rewarming, to 50 W after 35 min, compared to -237 W and -163 W respectively, for
      forced-air warming. Forced-air warming attenuated afterdrop and the metabolic
      stress of shivering while maintaining an average rate of rewarming comparable to
      shivering. Forced-air warming is a safe, simple, noninvasive treatment and could
      be used effectively in an emergency medical facility, and possibly in some
      rescue/emergency vehicles or marine vessels.

PMID- 7818449
TI  - Aerobic power and body size affects the exercise-induced stress hormone responses
      to varying water temperatures.
AB  - Eleven active male subjects were used to examine the effects of anthropometrics
      and aerobic power (VO2max) on the plasma cortisol (CO) and urine excretion of
      catecholamines (NE and E) and dopamine (D) during exercise in differing water
      temperatures. Each performed 30 min of cycle ergometer exercise at 60% VO2max
      while immersed to the neck in 20, 25, 30, and 35 degrees C water (Tw). The change
      in core temperature (delta Tre) during exercise was related to Tw (p < 0.007).
      Plasma CO (exercise - rest) increased during the 20 degrees C trials and
      decreased during the 30 and 35 degrees C trials (p = 0.011). Catecholamines were
      generally higher during the 20 and 35 degrees C trials than the 25 and 30 degrees
      C trials, with significance for only D and NE during the 35 degrees C vs. 25
      degrees C trials (p < 0.05). Multiple regression analyses (MRA) with CO during
      the 20 degrees C trials revealed that VO2max and delta Tre were significant
      partial correlates (p < 0.05), while in 35 degrees C water body mass index and
      delta Tre were significant partial correlates (p < 0.05). MRAs with NE and E
      during the 20 degrees C trials indicated that body fat was the only consistent
      significant partial correlate. The MRA for NE and E during the 35 degrees C
      trials were not significant; however, the MRA for D was significant. These
      results indicate that in addition to the core temperature, anthropometrics, and
      aerobic power affect the exercise-induced stress hormone responses during
      exposures to cold and warm water.

PMID- 7818450
TI  - Energetics and mechanics for partial gravity locomotion.
AB  - The role of gravitational acceleration on human locomotion is not clearly
      understood. It is hypothesized that the mechanics and energetics of locomotion
      depend upon the prevailing gravity level. A unique human-rated underwater
      treadmill and an adjustable ballasting harness were used to stimulate partial
      gravity environments. This study has two research aspects, biomechanics and
      energetics. Vertical forces which are exerted by subjects on the treadmill
      mounted, split-plate force platform show that peak vertical force and stride
      frequency significantly decrease (p < 0.05) as the gravity level is reduced,
      while ground contact time is independent of gravity level. A loping gait is
      employed over a wide range of speeds (approximately 1.5 m/s to approximately 2.3
      m/s) suggesting a change in the mechanics for lunar (1/6 G) and Martian (3/8 G)
      locomotion. As theory predicts, locomotion energy requirements for partial
      gravity levels are significantly less than at 1 G (p < 0.05).

PMID- 7818451
TI  - Alcohol-induced conditioned taste aversions in chemically labyrinthectomized
      rats.
AB  - Male rats were chemically labyrinthectomized (n = 22) by intratympanic injections
      of sodium arsanilate, and control rats (n = 15) received intratympanic injections
      of isotonic saline. All rats were tested for labyrinthine integrity and then
      adjusted to a 23 h.d-1 water deprivation schedule. Both labyrinthectomized and
      control rats were exposed to a conditioned taste aversion (CTA) procedure or a
      control procedure. The CTA technique involved pairing a novel saccharin taste
      with subsequent intraperitoneal injection of ethanol (1.5 g.kg-1; 15% solution).
      The control CTA procedure paired a novel saccharin taste with injections of
      isotonic saline. Following two conditioning trials and 3 d of water only,
      saccharin preference ratios were obtained in two-bottle choice tests (saccharin
      vs. water) over 4 consecutive days. Control rats conditioned with ethanol
      exhibited a strong CTA (p < 0.01) relative to control rats injected with saline.
      Labyrinthectomized rats drinking saccharin followed by ethanol injections showed
      a strong CTA (p < 0.01) if conditioning occurred 29-30 d post-labyrinthectomy.
      However, CTA's were not apparent in labyrinthectomized rats conditioned with
      ethanol 19 d post-labyrinthectomy. Thus, ethanol-induced CTA formation varied
      across the post-labyrinthectomy time period.

PMID- 7818452
TI  - Structural and biochemical properties of the rat myocardium after 21 days of head
      down suspension.
AB  - The effects of 21 d of head-down suspension on the biochemical and structural
      properties of the myocardium were determined in male rats (HDS, n = 10), and
      compared with control non-suspended animals (C, n = 10). HDS rats were prepared
      using Morey's tail-suspension model, and maintained at 45 degrees tilt. At the
      end of the conditioning period, hearts were excised and dissected into right (RV)
      and left plus intraventricular septum (LV). We observed that HDS rats had lower
      LV- and RV-absolute weights than C animals (-8.5%, p < 0.05, and -12%, p < 0.05,
      respectively). The relative ventricle weights (ventricle weight/body weight, mg.g
      1) were unaffected by HDS. Native myosin isoform analysis revealed that HDS did
      not alter myosin expression in both LV and RV. The capillary bed, examined using
      histochemical methods, was found to be unaffected by HDS. A significant decrease
      in the lactate dehydrogenase activity was detected in LV after 21 d of HDS (-16%,
      p < 0.05). Collectively, these results suggest that the early neurohumoral
      changes occurring in response to HDS-induced hemodynamic overload are sufficient
      to prevent any alteration in the biochemical and structural properties of the
      myocardial tissue.

PMID- 7818453
TI  - Thymoma in a Royal Air Force pilot--an unusual cause of chest pain.
AB  - The case history of a pilot with an anterior mediastinal tumor is described.
      Histology showed this to be a lymphocytic thymoma. An associated peripheral T
      cell lymphocytosis was present; total white cell count (WCC) was elevated for 7
      years prior to diagnosis and continued for 2 years post-resection. This has not
      been previously described in association with a cytologically benign non-invasive
      thymoma. The pathology of thymomas and the implications in this case are
      discussed.

PMID- 7818454
TI  - Wireless communication technology applied to disaster response.
AB  - Communication during disasters is frequently inadequate. In addition to having
      competent communication skills, medical responders must have access to adequate,
      effective, and reliable communications equipment. Wireless communication
      technologies are rapidly evolving. The medical community needs a basic
      understanding of existing and emerging technologies to fully exploit these new
      resources. Wireless communication technologies for disaster response include
      radio pagers, radios, cellular telephones, satellite communications, and personal
      communication services. This article explores concepts of each of these
      technologies, basic descriptions of current and future equipment, applications of
      the equipment to medical disaster response, and advantages and disadvantages of
      each technology.

PMID- 7818455
TI  - Measurement of night vision goggle (NVG) visual acuity with the NVG resolution
      chart.
AB  - Night vision goggles (NVG) operations are characterized as stressful with high
      task loading. Any reduction in goggle or visual performance which goes undetected
      can have a serious effect on flight safety and operational capability. The NVG
      Test Lane, with its resolution chart, provides an effective cost-efficient method
      for aircrew members to quickly evaluate the correct positioning and focusing of
      their NVG's prior to each mission. This evaluation validated the ability of the
      NVG resolution chart to produce the same performance results as a more detailed
      psychophysical procedure. NVG visual acuity was measured for five subjects (four
      pilots and one non-pilot) with two different night vision goggles. The results
      supported that there is no statistical difference between the results obtained
      with the individual target format and the 3 x 3 format. Additionally, the pilots
      with current NVG experience were able to obtain a significantly better acuity
      level than were those without current NVG experience.

PMID- 7818456
TI  - Volatile organic contaminants found in the habitable environment of the Space
      Shuttle: STS-26 to STS-55.
AB  - The health and performance of spacecraft crews can be adversely affected by
      contaminants present in the respirable air. Contaminants originate from hardware
      offgassing, crew and microbial metabolism, use of utility chemicals, leakage from
      fluid systems and payload experiments, and from electrical overheating. The
      quality of Shuttle air is measured by collecting contaminants in evacuated
      cylinders or on sorbent resin for later ground-based analysis by gas
      chromatography (GC) and GC mass spectrometry (MS). The results of those analyses
      are presented for 28 missions, including 5 Spacelabs which were flown in the
      payload bay of the Shuttle. The major contaminants were relatively nontoxic
      alcohols (ethanol, isopropanol), ketones (acetone, diacetone alcohol), alkanes,
      halocarbons (Halon 1301, Freon 113), and siloxanes. Occasionally, more toxic
      contaminants, such as methanol, acetaldehyde, and tetrachloroethene, were present
      at low concentrations (below 1 mg/m3). The contaminant concentrations measured in
      spacecraft air were compared to spacecraft maximum allowable concentrations
      (SMAC's) which are set to protect the crew from adverse health effects or
      performance decrements. Aggregate toxicity assessments (T values) of the
      contaminants present during each mission, calculated by summing the ratios of
      measured concentrations to each contaminant's SMAC, showed that air quality
      consistent met the criterion that the T value be less than 1.

PMID- 7818457
TI  - Combat stress, combat fatigue, and psychiatric disability in aircrew.
AB  - A survey of the literature reveals little data regarding modern aviation and
      combat-related stress, fatigue, or psychiatric disabilities. What little is known
      about combat fatigue in aircrew is largely inferred from literature written about
      ground personnel. Understanding the unique aviation environment is necessary in
      order to develop effective combat fatigue prevention programs. This paper reviews
      and summarizes the literature regarding aeromedical aspects of combat stress
      reactions. Combat stress, fatigue, and psychiatric disabilities are common
      battlefield conditions, but are largely preventable. If not prevented or treated
      appropriately, combat stress reactions will frequently lead to more serious
      psychiatric disabilities, causing the evacuation of the combatant away from his
      or her unit with no expectation of return to duty. Appropriate intervention using
      the basic principles of proximity, immediacy, and expectancy are crucial in
      reducing these casualties and returning aviation personnel to combat duty.

PMID- 7818458
TI  - Recurrent loss of consciousness in an aircrew member--a controllable cause.
AB  - A healthy 38-year-old technician aircrewman gave a 3-month history of recurrent
      loss of consciousness. Treatment for presumptive post-traumatic epilepsy was
      unsuccessful. Repeated cardiac investigation was negative until an episode of
      unconsciousness while instrumentated with a "Cardio-memo" recorder showed that an
      attack was accompanied by cardiac asystole. Further (invasive) cardiac
      investigations including electrophysiological studies were normal. Insertion of a
      dual chamber pacemaker (mode DDD) prevented any further attacks over a period of
      4 years' observation. He was found fit to resume restricted flying duties and has
      experienced no problems in the air or elsewhere.

PMID- 7818459
TI  - A unique flight experience in light of a volcano.

PMID- 7818460
TI  - Cardiovascular screening and HDL cholesterol.

PMID- 7818461
TI  - Coma in mild hypothermia.

PMID- 7818463
TI  - Adenovirus-mediated delivery into myocytes of muscle glycogen phosphorylase, the
      enzyme deficient in patients with glycogen-storage disease type V.
AB  - The feasibility of using adenovirus as a vector for the introduction of glycogen
      phosphorylase activity into myocytes has been examined. We used the C2C12
      myoblast cell line to assay the impact of phosphorylase gene transfer on myocyte
      glycogen metabolism and to reproduce in vitro the two strategies proposed for the
      treatment of muscle genetic diseases, myoblast transplantation and direct DNA
      delivery. In this study, a recombinant adenovirus containing the muscle glycogen
      phosphorylase cDNA transcribed from the cytomegalovirus promoter (AdCMV-MGP) was
      used to transduce both differentiating myoblasts and nondividing mature myotube
      cells. Muscle glycogen phosphorylase mRNA levels and total phosphorylase activity
      were increased in both cell types after viral treatment although more efficiently
      in the differentiated myotubes. The increase in phosphorylase activity was
      transient (15 days) in myoblasts whereas in myotubes higher levels of
      phosphorylase gene expression and activity were reached, which remained above
      control levels for the duration of the study (20 days). The introduction of
      muscle phosphorylase into myotubes enhanced their glycogenolytic capacity. AdCMV
      MGP-transduced myotubes had lower glycogen levels under basal conditions. In
      addition, these engineered cells showed more extensive glycogenolysis in response
      to both adrenaline, which stimulates glycogen phosphorylase phosphorylation, and
      carbonyl cyanide m-chlorophenylhydrazone, a metabolic uncoupler. In conclusion,
      transfer of the muscle glycogen phosphorylase cDNA into myotubes confers an
      enhanced and regulatable glycogenolytic capacity. Thus this system might be
      useful for delivery of muscle glycogen phosphorylase and restoration of
      glycogenolysis in muscle cells from patients with muscle phosphorylase deficiency
      (McArdle's disease).

PMID- 7818462
TI  - Phosphatidic acid activation of protein kinase C-zeta overexpressed in COS cells:
      comparison with other protein kinase C isotypes and other acidic lipids.
AB  - Phosphatidic acid (PA) is produced rapidly in agonist-stimulated cells, but the
      physiological function of this PA is unknown. We have examined the effects of PA
      on distinct isoforms of protein kinase C (PKC) using a new cell-free assay
      system. Addition of PA to cytosol from COS cells overexpressing PKC-alpha, 
      epsilon or -zeta differentially-activated all three isotypes, as shown by PKC
      autophosphorylation, and prominent phosphorylation of multiple endogenous
      substrates. In the absence of Ca2+, the diacylglycerol-insensitive zeta-isotype
      of PKC was most strongly activated by both PA and bisPA, a newly identified
      product of activated phospholipase D, with each lipid inducing its own profile of
      protein phosphorylation. BisPA was also a strong activator of PKC-epsilon, but a
      weak activator of PKC-alpha. Ca2+, at > or = 0.1 microM, inhibited PA and bisPA
      activation of PKC-zeta, but did not affect PKC-epsilon activation. In contrast,
      PKC-alpha was strongly activated by PA only in the presence of Ca2+. BisPA
      induced phosphorylations mediated by PKC-zeta could be mimicked in part by other
      acidic phospholipids and unsaturated fatty acids. PA activation of PKC-zeta was
      unique in that PA not only stimulated PKC-zeta-mediated phosphorylation of
      distinctive substrates, but also caused an upward shift in electrophoretic
      mobility of PKC-zeta, which was not observed with other acidic lipids or with PKC
      alpha or -epsilon. We have presented evidence that this mobility shift is not
      caused by PKC-zeta autophosphorylation, but it coincides with physical binding of
      PA to PKC-zeta. These results suggest that in cells stimulated under conditions
      where intracellular Ca2+ is at (or has returned to) basal level, PA may be a
      physiological activator of PKC-zeta.

PMID- 7818464
TI  - Rescue of the complex temperature-sensitive phenotype of Chinese hamster ovary
      E36ts20 cells by expression of the human ubiquitin-activating enzyme cDNA.
AB  - The ubiquitin conjugation system is a multi-step pathway in which ubiquitin is
      activated and conjugated to acceptor proteins, one function of which is to target
      acceptor proteins for rapid degradation within the cell. The conjugation system
      is involved in many aspects of cellular functions, including the cell cycle.
      Several cell-cycle arrest mutant cell lines have been characterized and appear to
      harbour a mutant ubiquitin-activating enzyme, E1, as their primary defect. One
      such cell line is ts20, which is derived from Chinese hamster ovary E36 cells.
      This cell line has been used to characterize some of the potential functions of
      the ubiquitin conjugation system in vivo, such as its involvement in the
      maturation of autophagic vacuoles. The present study describes the complete
      rescue of the complex ts20 phenotype following the expression of the cDNA for
      human E1. Stable transfectants expressing the human E1 cDNA in the CMVneo
      expression vector were measured for ubiquitin-conjugation activity, protein
      degradation and growth in culture at the nonpermissive temperature. This rescue
      confirms that the phenotype observed in the ts20 cells is due to a defect in the
      E1 enzyme. Thus, the ts20 cell line will serve as a useful tool to delineate the
      functions of the ubiquitin system in vivo.

PMID- 7818465
TI  - Association constants for the binding of vancomycin and teicoplanin to N-acetyl-D
      alanyl-D-alanine and N-acetyl-D-alanyl-D-serine.

PMID- 7818466
TI  - The structure and function of methanol dehydrogenase and related quinoproteins
      containing pyrrolo-quinoline quinone.

PMID- 7818467
TI  - Cyclic AMP-induced mucin exocytosis is independent of Cl- movements in human
      colonic epithelial cells (HT29-Cl.16E).
AB  - The human colonic epithelial goblet cell line HT29-Cl.16E was used to test
      whether stimulated Cl- transport is involved in the mucin exocytotic response to
      an increase in intracellular cyclic AMP by measuring in parallel the short
      circuit current (Isc) and mucin exocytosis. Addition of 50 microM forskolin to
      HT29-Cl.16E cells resulted in a 2-fold stimulation of mucin release and an
      increase in Isc by 20 microA/cm2. To evaluate the requirement for cosecretion of
      Cl-, the Cl- flux was altered by three different manipulations: (1) Cl- in the
      medium was replaced by the poorly transported anion gluconate; (2) basolateral Cl
      influx through the Na(+)-K(+)-2Cl- cotransporter was inhibited by bumetanide;
      and (3) an inward Cl- flux through the apical plasma membrane was generated by
      reversing the Cl- gradient. These manipulations did not change the forskolin
      stimulated mucin release and thereby provide evidence that Cl- movements are not
      required for fusion of mucin granules with the plasma membrane.

PMID- 7818468
TI  - Overexpression of inositol 1,4,5-trisphosphate 3-kinase in Xenopus oocytes
      inhibits agonist-evoked capacitative calcium entry.
AB  - Ins(1,4,5)P3 3-kinase is a key enzyme in the regulation of Ins(1,4,5)P3.
      Overexpression of Ins(1,4,5)P3 3-kinase inhibited agonist-evoked and
      Ins(1,3,4,5)P4-evoked Ca2+ entry in Xenopus oocytes, but did not inhibit Ca2+
      entry evoked by thapsigargin or non-metabolizable Ins(1,4,5)P3 analogues. The
      data suggest that Ins(1,4,5)P3 alone plays the crucial role in the activation of
      capacitative Ca2+ entry by emptying intracellular stores.

PMID- 7818469
TI  - Purification, cDNA cloning and heterologous expression of the human mitochondrial
      NADP(+)-dependent malic enzyme.
AB  - Mitochondrial NADP(+)-dependent malic enzyme (ME; EC 1.1.1.39) has been purified
      to homogeneity and characterized kinetically from bovine heart. Partial amino
      acid sequence information allowed amplification of a specific bovine cDNA, which
      was used to isolate a full-length human cDNA of this isoform of ME. The cDNA is
      1930 bp long and codes for a protein of 604 amino acids. Comparison of the amino
      acid sequence of this isoform with published sequences of other human ME isoforms
      shows stretches of homology interrupted by larger regions with significant
      differences. The human protein has been expressed in Escherichia coli, and the
      recombinant human protein has the same kinetic properties as the corresponding
      protein purified from bovine heart. Northern blot analysis showed a strong tissue
      specific transcription with a predominantly high expression-rate in organs with a
      low division-rate.

PMID- 7818470
TI  - Repair of abasic sites by mammalian cell extracts.
AB  - Hamster cell extracts that perform repair synthesis on covalently closed circular
      DNA containing pyrimidine dimers, were used to study the repair of
      apurinic/apyrimidinic (AP) sites and methoxyamine (MX)-modified AP sites. Plasmid
      molecules were heat-treated at pH 5 and incubated with MX when required. The
      amount of damage introduced ranged from 0.2 to 0.9 AP sites/kb. Extracts were
      prepared from the Chinese hamster ovary CHO-9 cell line and from its derivative,
      43-3B clone which is mutated in the nucleotide excision repair (NER) ERCC1 gene.
      AP and MX-AP sites stimulated repair synthesis by CHO-9 cell extracts. The level
      of synthesis correlated with the number of lesions and was of similar magnitude
      to the repair stimulated by 4.3 u.v. photoproducts/kb. Repair of AP and MX-AP
      sites was faster than the repair of u.v. damage and was independent of ERCC1 gene
      product. The high level of repair replication was due to a very efficient and
      rapid incision of plasmids carrying AP or MX-AP sites, performed by abundant AP
      endonucleases present in the extract. The calculated average repair patch sizes
      were: 7 nucleotides per AP site; 10 nucleotides per MX-AP site; 28 nucleotides
      per (6-4) u.v. photoproduct or cyclobutane pyrimidine dimer. The data indicate
      that AP and MX-AP sites are very efficiently repaired by base-excision repair in
      mammalian cells and suggest that MX-AP sites may also be processed via
      alternative repair mechanisms.

PMID- 7818471
TI  - Mitochondrial metabolism of a hydroperoxide to free radicals in human endothelial
      cells: an electron spin resonance spin-trapping investigation.
AB  - Oxidative damage to the vascular endothelium may be an important event in the
      promotion of atherosclerosis. Several lines of evidence suggest that lipid
      hydroperoxides may be responsible for the induction of such damage.
      Hydroperoxides cause loss of endothelial cell integrity, increase the
      permeability of the endothelium to macromolecules, and compromise its ability to
      control vascular tone via the secretion of vasoactive molecules in response to
      receptor stimulation. The molecular mechanisms responsible for these effects are,
      however, poorly understood. In this paper, we describe an e.s.r. spin-trapping
      investigation into the metabolism of the model hydroperoxide compound tert
      butylhydroperoxide to reactive free radicals in intact human endothelial cells.
      The hydroperoxide is shown to undergo a single electron reduction to form free
      radicals. Experiments with metabolic poisons indicate that the mitochondrial
      electron-transport chain is the source of electrons for this reduction. The metal
      ion-chelating agent desferrioxamine was found to prevent cell killing by tert
      butylhydroperoxide, but did not affect free radical formation, suggesting that
      free metal ions may serve to promote free-radical chain reactions involved in
      cell killing following the initial conversion of the hydroperoxide to free
      radicals by mitochondria. These processes may well be responsible for many of the
      reported effects of hydroperoxides on endothelial cell integrity and function.

PMID- 7818472
TI  - Binding of high-molecular-mass kininogen to the Apple 1 domain of factor XI is
      mediated in part by Val64 and Ile77.
AB  - We have previously demonstrated the presence of a binding site for high-molecular
      mass kininogen (HK), spanning residues Val59-Lys83, in the first Apple (A1)
      domain in the heavy-chain region of factor XI. We have now prepared
      conformationally constrained synthetic peptides and recombinant A1 domain (rA1)
      constructs to identify the specific amino acid residues that constitute the HK
      binding site. Expression of the A1 domain (Glu1-Ser90) was achieved in a
      bacterial expression system following PCR amplification of the A1 domain from
      factor XI cDNA and ligation into an expression plasmid. The rA1 inhibited factor
      XI binding to HK [Ki approximately (2-3) x 10(-7) M] in a manner
      indistinguishable from purified factor XI, indicating that all the information
      necessary for binding HK is contained within the A1 domain. To identify specific
      amino acid residues involved in binding HK, conformationally constrained peptides
      were synthesized containing conservative amino acid substitutions at residues
      suspected to contain side chains involved in binding, including Val64-->Ala,
      Glu66-->Ala, Arg73-->Ala and Ile77-->Ala. Because normal results were obtained
      with all peptides with the exception of Val64-->Ala and Ile77-->Ala, which failed
      to compete normally with factor XI for binding to HK, we prepared two mutant rA1
      domains (Val64-->Ala and Ile77-->Ala) by PCR-based site-directed mutagenesis,
      both of which exhibited diminished capacity to inhibit factor XI binding to HK.
      Competition studies with prekallikrein (PK) and a PK-dependent synthetic peptide
      suggested that PK and factor XI have a common surface in the A1 domain for
      binding HK of which Val64 is a part. We conclude that the binding of factor XI to
      HK is mediated at least in part by Val64 and Ile77 in the A1 domain of factor XI.

PMID- 7818473
TI  - Expression of reduced amounts of structurally altered aggrecan in articular
      cartilage chondrocytes exposed to high hydrostatic pressure.
AB  - The effect of hydrostatic pressure on proteoglycan (PG) metabolism of chondrocyte
      cultures was examined using a specially designed test chamber. Primary cultures
      of bovine articular chondrocytes at confluence were exposed for 20 h to 5 and 30
      MPa continuous hydrostatic pressures and 5 MPa hydrostatic pulses (0.017, 0.25
      and 0.5 Hz) in the presence of [35S]sulphate. Northern blot analyses showed that
      chondrocyte cultures used in this study expressed abundant mRNA transcripts of
      aggrecan, typical of chondrocytes, but not versican. The cultures also expressed
      biglycan and decorin. Enzymic digestions with keratanase and chondroitinases AC,
      ABC and B and subsequent SDS/agarose gel electrophoresis confirmed the synthesis
      of aggrecans and small dermatan sulphate PGs. The continuous 30 MPa pressure
      reduced total PG synthesis by 37% as measured by [35S]sulphate incorporation, in
      contrast to the 5 MPa continuous pressure which had no effect. The high static
      pressure also reduced total [3H]glucosamine incorporation by 63% and total
      [14C]leucine incorporation by 57%. The cyclic pressures showed a frequency
      dependent stimulation (0.5 Hz, 11%) or inhibition (0.017 Hz, -17%) of
      [35S]sulphate incorporation. Aggrecans secreted under continuous 30 MPa pressure
      showed a retarded migration in 0.75% SDS/agarose gel electrophoresis and they
      also eluted earlier on Sephacryl S-1000 gel filtration, indicative of a larger
      molecular size. The increased size was consistent with an increase of average
      glycosaminoglycan chain length as determined by Sephacryl S-300 gel filtration.
      No change in aggrecan size was observed with the lower (5 MPa) static or cyclic
      pressures. Continuous 30 MPa hydrostatic pressure slightly reduced the steady
      state mRNA level of aggrecan, in parallel with the decline in PG synthesis
      measured by [35S]sulphate incorporation. The results demonstrated that high
      hydrostatic pressure could influence the synthesis of PGs, especially of
      aggrecans, in chondrocytes both at the transcriptional and translational/post
      translational levels.

PMID- 7818474
TI  - A novel oligosaccharide, GlcA beta 1-4Xyl beta 1-(4-methylumbelliferone),
      synthesized by human cultured skin fibroblasts.
AB  - Human skin fibroblasts were cultured in the presence of 4-methylumbelliferyl-beta
      D-xyloside (Xyl-MU) using a mass-culture system with a microcarrier. The
      structures of Xyl-MU-induced sugars purified from the dialysable fraction of the
      incubation medium were investigated. In addition to glycosaminoglycans the
      elongation of which initiated by Xyl-MU has already been reported, and
      oligosaccharides similarly initiated by Xyl-MU, such as Gal-Gal-Xyl-MU, Gal-Xyl
      MU and SA-Gal-Xyl-MU, a novel Xyl-MU-induced oligosaccharide was detected. This
      oligosaccharide was identified as GlcA beta 1-4Xyl beta 1-(4-methylumbelliferone)
      using sugar composition analysis, enzyme digestion, mass spectrometry and Smith
      degradation. Using this culture system, the amount of the new oligosaccharide
      produced increased with the incubation time, even after the production of
      glycosaminoglycan initiated by Xyl-MU and Gal-Xyl-MU had reached a plateau. These
      results suggest that this oligosaccharide may be involved in terminating the
      elongation of glycosaminoglycan chains that is initiated by Xyl-MU.

PMID- 7818475
TI  - Biosynthesis of a human gall-bladder mucin.
AB  - Mucin glycoproteins play an important role in the initial stages of gall-stone
      formation by a currently largely unknown mechanism. Understanding the structure
      of gall-bladder mucin is necessary to comprehend the mechanism by which
      cholesterol monohydrate crystals aggregate. Three successive CsCl-gradient
      ultracentrifugation steps were used to purify human gall-bladder mucin from gall
      bladder tissue. The isolated macromolecules had a typical mucin-like
      monosaccharide composition and appeared as heterogeneous high-M(r) glycoproteins
      on SDS/PAGE. A polyclonal antiserum was raised against these molecules and the
      specificity of the antiserum was ascertained by immunoblotting. The antiserum
      specifically stained mucous granules at the apical side of all gall-bladder
      epithelial cells in neck, fundus and body. The antibody was subsequently used to
      immunoprecipitate the mucin and biosynthetic intermediates from gall-bladder
      tissue homogenates. An early biosynthetic precursor of the isolated mucin was
      identified by SDS/PAGE as a single polypeptide with an apparent M(r) of approx.
      470,000. This precursor protein was converted after 1 h into a heterogeneous high
      M(r) glycoconjugate with an electrophoretic mobility similar to that of the
      purified mucin. The mature mucin, but not the precursor, was secreted into the
      culture medium, starting at 1 h. As shown by SDS/PAGE under non-reducing
      conditions, the precursors form disulphide-linked oligomers. Using the N
      glycosylation inhibitor tunicamycin, the apparent M(r) of the precursor was
      decreased to approx. 410,000, indicating that N-linked glycan chains are attached
      to the precursor polypeptide.

PMID- 7818476
TI  - Cloning of rat asparagine synthetase and specificity of the amino acid-dependent
      control of its mRNA content.
AB  - A full-length cDNA clone for rat asparagine synthetase (AS) was isolated from a
      cDNA library enriched for amino acid-regulated sequences. The AS cDNA was used to
      investigate the amino acid-dependent repression of AS mRNA content in rat Fao
      hepatoma cells. In response to complete amino acid starvation, there was an
      approximately 10-fold increase in the level of AS mRNA. Three species of mRNA, of
      approx. sizes 2.0, 2.5 and 4.0 kb, were detected and each was simultaneously
      regulated to the same degree. The expression of AS mRNA increased by 6 h after
      removal of amino acids, reached a plateau after 9 h, and was blocked by either
      actinomycin D or cycloheximide. Partial repression of the AS mRNA content was
      maintained by the presence of a single amino acid in the culture medium, but the
      degree of effectiveness for each one varied widely. Glutamine showed the greatest
      ability to repress the AS mRNA content, even at an extracellular concentration 10
      times below its plasma level. Other effective repressors included the amino acids
      asparagine, histidine and leucine, as well as ammonia. Depletion of selected
      single amino acids from an otherwise complete culture medium also caused up
      regulation. In particular, removal of histidine, threonine or tryptophan from the
      medium, or the addition of histidinol to inhibit histidinyl-tRNA synthetase,
      resulted in a significant increase in AS mRNA content. The data indicate that
      nutrient regulation of AS mRNA occurs by a general control mechanism that is
      responsive to a spectrum of amino acids.

PMID- 7818477
TI  - The kinetics, substrate and inhibitor specificity of the lactate transporter of
      Ehrlich-Lettre tumour cells studied with the intracellular pH indicator BCECF.
AB  - 1. Suspensions of cultured Ehrlich-Lettre tumour cells were loaded with the pH
      sensitive fluorescent indicator 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein
      (BCECF), and changes in intracellular pH upon addition of L-lactate and other
      monocarboxylates were continuously monitored by fluorimetry using dual-wavelength
      excitation (450/500 nm) and single-wavelength emission (> 520 nm). 2. The rapid
      fluorescence changes were analysed by first-order regression analysis, and with
      suitable calibration procedures this enabled calculation of initial rates of
      proton uptake associated with monocarboxylate transport. 3. The stoichiometry was
      shown to be one proton per lactate molecule transported. 4. The kinetics of
      carrier-mediated transport of a wide range of monocarboxylates were determined at
      25 degrees C. The Km values for L-lactate, pyruvate and D-lactate were found to
      be 4.54, 0.72 and 27.5 mM respectively, similar to values found previously for
      rat erythrocytes. This similarity was shared with a wide range of variously
      substituted C2, C3 and C4 monocarboxylates, all of which were transported with
      similar Vmax. No stereoselectivity was found in the Km values for D- and L-2
      chloropropionate (0.75 mM) or D- and L-3-hydroxybutyrate (11 mM), but in the
      latter case the Vmax. of the D-isomer was twice that of the L-isomer. 5. The
      temperature-dependence of L-lactate transport demonstrated a transition point,
      with activation energies of 60 and 109 kJ.mol-1 above and below 19 degrees C
      respectively The Km for L-lactate below the transition temperature was about half
      that above it. 6. Inhibition of lactate transport into tumour cells by a wide
      range of compounds known to inhibit the erythrocyte monocarboxylate carrier was
      analysed. Patterns of inhibition were similar to those seen in the erythrocyte,
      but the Ki values were 2-4-fold higher in the tumour cells. 7. It is concluded
      that tumour cells contain an isoform of the monocarboxylate carrier with
      functional properties almost identical with that found in erythrocytes. This is
      probably identical with MCT1, which was recently cloned and sequenced from
      Chinese Hamster Ovary cells [Kim Garcia, Goldstein, Pathak, Anderson and Brown
      (1994) Cell 76, 865-873].

PMID- 7818478
TI  - Specific activation of beta-casein kinase by the inflammatory cytokines
      interleukin 1 and tumour necrosis factor.
AB  - Increases (5-fold) in the rate of phosphorylation of beta-casein were observed in
      extracts of human gingival fibroblasts that had been stimulated by interleukin 1
      (IL-1) or tumour necrosis factor (TNF). The induced kinase was cytosolic and had
      little activity on alpha-casein. Its chromatographic behaviour on anion-exchange
      and gel-filtration columns was similar to that of beta-casein kinase, an enzyme
      detected originally in MRC-5 cells stimulated by IL-1 and TNF. Phosphopeptide
      maps of beta-casein confirmed that the kinase activated in gingival fibroblasts
      had the same substrate specificity as beta-casein kinase. In gingival
      fibroblasts, beta-casein kinase activity was maximum after 15 min of stimulation
      by IL-1 or TNF, and remained activated for several hours. Activations of small
      heat-shock protein (hsp27) kinase and mitogen-activated protein (MAP) kinase were
      also maximum 15 min after stimulation, but decreased to background levels within
      the next 30 min. Study of the effects of 21 agents other than IL-1 or TNF showed
      that none activated beta-casein kinase, whereas several activated MAP kinase or
      hsp27 kinase. beta-Casein kinase was also detected in extracts of bovine
      articular chondrocytes and human endothelial cells stimulated by IL-1 or TNF.
      Semi-purified preparations of fibroblast beta-casein kinase were not inactivated
      by phosphatases in vitro. Our results suggest that it may be involved in
      responses specific to IL-1 and TNF in a wide range of cell types and that its
      activation probably involves mechanisms other than its phosphorylation.

PMID- 7818479
TI  - Mobilization of intracellular Ca2+ by adenine nucleotides in human T-leukaemia
      cells: evidence for ADP-specific and P2y-purinergic receptors.
AB  - The expression of purinergic receptors on human T-cells was investigated and the
      receptors were shown to be functionally coupled to intracellular signals in two
      out of eight T-leukaemia cell-lines. Addition of adenine nucleotides resulted in
      mobilization of intracellular Ca2+ in HPB-ALL cells and a cell line (CB1)
      recently isolated from a patient with T-acute lymphoblastic leukaemia. Of a range
      of nucleotides tested only ADP and ATP elevated intracellular levels of Ca2+,
      with ADP being the more potent agonist. Ca2+ mobilization by ATP was accompanied
      by increased inositol phosphate production and was blocked by the purinergic
      receptor antagonist, Reactive Blue 2, indicating that ATP was interacting with a
      P2y receptor. Intracellular Ca2+ release triggered by ADP was independent of both
      inositol phosphate production and protein tyrosine phosphorylation. Expression of
      the transmembrane phosphotyrosine phosphatase, CD45, had no effect on ADP
      stimulated Ca2+ mobilization. Our results show that functional P2y receptors can
      be expressed on T-cells, and also identify a novel T-cell ADP receptor. Signals
      mediated by these purinergic receptors could play important roles in modulating T
      cell function.

PMID- 7818480
TI  - Specificity and localization of lipolytic activity in adult Drosophila
      melanogaster.
AB  - The triacylglycerol lipases present in adult Drosophila melanogaster have been
      investigated. Different lipase activities are present in various tissues in the
      fly. In particular, an abundant lipase activity is present in the male accessory
      gland. An esterase null mutant was used to confirm that the enzyme activity was
      due to a distinct lipase and not non-specific activity from esterase 6 which is
      also abundant in accessory glands. The properties of the accessory-gland lipase
      were investigated, and pH optima and substrate utilization suggest that it has
      some similarities to vertebrate bile-salt-stimulated lipase. Lipase activity is
      significantly reduced in males and increased in females shortly after mating.
      This finding suggests that lipase activity is transferred to the female and may
      be important in mating and reproduction in Drosophila.

PMID- 7818481
TI  - Incorporation of carbon from photosynthetic products into 2-carboxyarabinitol-1
      phosphate and 2-carboxyarabinitol.
AB  - The synthesis of 2-carboxy-D-arabinitol-1-phosphate (CA1P), the naturally
      occurring inhibitor of ribulose-1,5-bisphosphate carboxylase/oxygenase, was
      studied in leaves of the French bean Phaseolus vulgaris, L. Leaves were supplied
      with air containing 14CO2 in the light then the plants were transferred to normal
      air in the light or in the dark. Leaf samples were frozen in liquid nitrogen,
      ground to a powder and extracted with acid. Lipids, pigments and cations were
      removed from the extract and CA1P and 2-carboxy-D-arabinitol (CA) recovered by
      anion exchange chromatography. The CA1P was further purified by its specific
      binding to purified ribulose-1,5-bisphosphate carboxylase/oxygenase. CA and CA1P
      were identified by chromatographic properties and n.m.r. spectra. When plants
      were kept for 15 h in darkness after exposure to 14CO2, up to 2.2% and 5.5% of
      the radioactivity in the extracts was present in CA1P and CA, respectively. The
      most radioactivity appeared in these compounds when photosynthesis from 14CO2
      took place at low photosynthetic photon flux density (PPFD). Under such
      conditions, radioactivity was detected in CA1P after only 10 min. During
      subsequent exposure to normal air (12CO2) at low PPFD the amount of radioactivity
      in CA1P remained almost constant for 6 h; in darkness the rate of incorporation
      of radioactivity into CA1P reached a maximum after 2 h and the radioactivity was
      still increasing 6 h later. At low PPFD, the amount of CA1P in the leaves reached
      a maximum after 2 h. In darkness, the amount of CA1P began to increase rapidly
      after a lag of almost 1 h, well ahead of the increase in radioactivity in CA1P.

PMID- 7818482
TI  - Isolation and characterization of cDNA for human 120 kDa mitochondrial 2,4
      dienoyl-coenzyme A reductase.
AB  - 2,4-Dienoyl-CoA reductase (EC 1.3.1.34) participates in beta-oxidation of
      (poly)unsaturated enoyl-CoAs and it appears in mammalian mitochondria as two
      isoforms with molecular masses of 120 and 60 kDa [Hakkola and Hiltunen (1993)
      Eur. J. Biochem. 215, 199-204]. The 120 kDa isomer is a homotetrameric enzyme,
      and here we report cDNA cloning of its subunit from human. cDNA clones were
      isolated by reverse transcriptase-PCR from a fibrosarcoma cell line and by
      screening from a human liver lambda gt11 cDNA library. The 1128 bp clone
      contained an open reading frame of 1008 bp encoding a polypeptide of 335 amino
      acid residues with a predicted molecular mass of 36066 Da. This polypeptide
      represents the immature monomer of the 120 kDa enzyme, and it contains a
      predicted N-terminal mitochondrial targeting signal. The amino acid (nucleotide)
      sequence of human 2,4-dienoyl-CoA reductase shows 82.7% (81.7%) similarity
      (identity) to the corresponding sequence from the rat. Northern-blot analysis
      gave a single mRNA species of 1.2 kb in several human tissues, the amounts
      present in the tissues tested ranking as follows: heart approximately liver
      approximately pancreas > kidney >> skeletal muscle approximately lung.
      Immunoblotting of human and rat liver samples with an antibody to the subunit of
      the rat 120 kDa isoform indicates that the mature human enzyme is larger than its
      counterpart in the rat. The comparison of amino acid sequences for rat and human
      enzymes proposes that the difference in the size is 10 amino acid residues. The
      results show that the rat and human reductases are similar in many
      characteristics and that the reductase is expressed in human tissues capable of
      beta-oxidation of fatty acids.

PMID- 7818484
TI  - Regulation of an in vivo metal-exchangeable superoxide dismutase from
      Propionibacterium shermanii exhibiting activity with different metal cofactors.
AB  - The anaerobic, but aerotolerant Propionibacterium freudenreichii sp. shermanii
      contains a single superoxide dismutase [EC 1.15.1.1.] exhibiting comparable
      activity with iron or manganese as metal cofactor. The formation of superoxide
      dismutase is not depending on the supplementation of iron or manganese to the
      culture medium. Even in the absence of these metals the protein is built in
      comparable amounts. Bacteria grown in the absence of iron and manganese
      synthesize a superoxide dismutase with very low activity which had incorporated
      copper. If the medium was also depleted of copper, cobalt was incorporated,
      leading to an enzymically inactive form. In the absence of cobalt an enzymically
      inactive superoxide dismutase was built with unknown metal contents. Upon
      aeration the amount of superoxide dismutase activity increased continuously up to
      9 h, due to a de novo synthesis of the protein. This superoxide dismutase had
      incorporated iron into the active centre. The superoxide dismutase of
      Propionibacterium shermanii is able to form a much wider variety of complexes
      with trace metal ions in vivo than previously recognized, leading to the
      hypothesis that the original function of these proteins was the binding of
      cytoplasmic trace metals present in excess.

PMID- 7818483
TI  - Lytic anti-alpha-galactosyl antibodies from patients with chronic Chagas' disease
      recognize novel O-linked oligosaccharides on mucin-like glycosyl
      phosphatidylinositol-anchored glycoproteins of Trypanosoma cruzi.
AB  - Sera of patients with chronic Chagas' disease (American trypanosomiasis) contain
      elevated levels of anti-alpha-galactosyl antibodies that are lytic to Trypanosoma
      cruzi. The T. cruzi trypomastigote F2/3 antigen complex recognized by these
      antibodies runs as a broad smear on SDS/PAGE [Almeida, Krautz, Krettli and
      Travassos (1993) J. Clin. Lab. Anal. 7, 307-316]. Treatment of T. cruzi
      trypomastigote cells with bacterial phosphatidylinositol-specific phospholipase C
      (PI-PLC) abolished most of their reactivity to chronic Chagas'-disease
      ((Chagasic, Ch) anti-alpha-galactosyl antibodies (anti-Gal). The F2/3 antigen
      complex, purified by solvent extraction and hydrophobic-interaction
      chromatography, contained 60% carbohydrate by weight and substantial amounts of
      Thr, Ser, Glx, Asx, Gly, Ala and Pro, but relatively few hydrophobic amino acids.
      The presence of myoinositol, ethanolamine and 1-O-hexadecylglycerol suggested the
      presence of glycosyl-phosphatidylinositol membrane anchors. This was confirmed by
      PI-PLC treatment, which rendered the F2/3 molecules hydrophilic and reactive to
      anti-(cross-reacting determinant) antibodies. The majority of the GlcNAc content
      of the F2/3 antigens was found at the reducing termini of oligosaccharides in O
      glycosidic linkage to Thr residues. These O-linked oligosaccharides could be
      released by beta-elimination and by mild hydrazinolysis. The smallest released
      oligosaccharitol that was reactive with the Ch anti-Gal was Gal alpha 1-3Gal beta
      1-4GlcNAcol (where GlcNAcol is N-acetyl-glucosaminitol). Several other Gal
      containing oligosaccharitols were observed, most of which were branched and
      contained 4,6-di-O-substituted GlcNAcol at their reducing termini. About half of
      the total released oligosaccharitols could bind to immobilized Ch anti-Gal, but
      none of them bound to the anti-Gal isolated from normal human sera. These data
      suggest that the specificities of the Ch anti-Gal are quite different from the
      natural anti-Gal isolated from normal human sera. Therefore, these novel T. cruzi
      O-linked oligosaccharides are highly immunogenic under the conditions of natural
      infection and are the targets for lytic Ch anti-Gal.

PMID- 7818485
TI  - Inactive membrane protein kinase Cs: a possible target for receptor signalling.
AB  - The activation of the multifunctional cell signalling enzymes, the protein kinase
      Cs (PKCs), is generally thought to result from the translocation of inactive
      cytosolic enzymes to activation sites in cell membranes. However, recent studies
      suggest that PKCs may also be stimulated in cells by processes independent of
      translocation. One possible mechanism is the modulation of the activity of PKCs
      already resident in membranes. A PKC assay that measures enzyme activity directly
      in isolated native membranes has revealed the presence of an activatable pool of
      PKCs resident in native membranes of various cells and tissues. In 3T3-L1 cells,
      some or all of this pool of membrane PKCs was stimulated within 10 min of
      exposing the cells to 10 ng/ml epidermal growth factor or 100 ng/ml fibroblast
      growth factor. Similar increases in PKC activity were observed in native
      membranes isolated from CTLL-2, WEHI-231 and S49 lymphoma cells that had been
      exposed to interleukin-2. These growth factors all stimulated membrane PKC
      activity without detectably translocating cytosolic enzymes to the membranes. In
      intact WEHI cells, low concentrations (5-10 microM) of a diacylglycerol, 1-oleoyl
      2-acetyl-sn-glycerol (OAG), or low concentrations (2-10 nM) of phorbol 12
      myristate 13-acetate sufficed to activate PKCs already resident in membranes, but
      much higher concentrations (50-100 microM and 50-100 nM respectively) were needed
      to detectably stimulate the translocation of cytosolic PKCs. A
      phosphatidylcholine-specific phospholipase C also selectively stimulated membrane
      PKCs in WEHI cells at concentrations that were much less than those needed to
      induce the translocation of cytosolic enzymes. Furthermore, interleukin-2 and low
      concentrations of OAG both stimulated the phosphorylation of the 85 kDa PKC
      selective substrate protein in intact WEHI cells in which translocation of PKCs
      was not evident. These results suggest that the membranes of some cells maintain
      a pool of activatable PKCs that respond to lower levels of extracellular stimuli
      than cytosolic PKCs, and that can be stimulated by signals which produce
      diacylglycerols through the hydrolysis of phospholipids other than
      polyphosphoinositides.

PMID- 7818486
TI  - Activation of Ito cells involves regulation of AP-1 binding proteins and
      induction of type I collagen gene expression.
AB  - Activation of liver Ito cells is characterized by increased proliferation,
      fibrogenesis, loss of cellular retinoid and change of cell-shape. Here, we have
      described fundamental differences between freshly isolated Ito cells (FIC) and
      long-term cultured Ito cells (LTIC). This process of activation correlates with
      the absence of expression of Pro alpha 1(I) gene in FIC. LTIC expressed abundant
      transcripts of Pro alpha 1(I) gene. Nuclear run-off experiments showed the
      inability of FIC to support Pro alpha 1(I) RNA transcription while LTIC
      transcribed it greater than 5-fold as compared with FIC. Transforming growth
      factor beta (TGF beta)-treated LTIC had a preferential increase in the rate of
      Pro alpha 1(I) gene transcription as compared with control LTIC. A human collagen
      type I promoter-enhancer construct (pCOL-KT) [Thompson, Simkevich, Holness, Kang
      and Raghow (1991) J. Biol. Chem. 266, 2549-2556] was readily expressed in LTIC
      but failed to be expressed in FIC. Furthermore, TGF beta treatment of LTIC
      resulted in an increased expression of pCOL-KT. The deletion of an activator
      protein-1 (AP-1) binding site (+598 to +604) in the 360 bp enhancer region of
      pCOL-KT (S360) caused decreased expression of the CAT reporter gene, suggesting
      that this bonafide AP-1 site can, at least in part, mediate the transactivation
      effect of TGF beta. Using DNAase I protection, we demonstrate a single foot-print
      located at +590 to +625 in the S360 fragment; nuclear extracts prepared from TGF
      beta-treated LTIC exhibited greater activity of these AP-1 binding proteins. Gel
      mobility assays corroborated and extended the footprinting observation. No AP-1
      binding activity was found in the nuclear extracts of FIC. Double-stranded
      oligonucleotides containing the consensus AP-1 motif were able to compete out the
      binding; consensus NF-1 motif oligonucleotides failed to do so. The preincubation
      of nuclear extracts from control and TGF beta-treated LTIC with antibodies
      against c-jun and c-fos rendered a reduced binding of AP-1 proteins to the target
      S360 fragment.

PMID- 7818487
TI  - Modification of glutathione S-transferase 3-3 mutants with 2-(S-glutathionyl)
      3,5,6-trichloro-1,4-benzoquinone. Identification of the C-terminal tryptic
      fragment as part of the H-site and evidence that 2-(S-glutathionyl)-3,5,6
      trichloro-1,4-benzoquinone is not specific for cysteine labelling.
AB  - A triple mutant of rat liver glutathione S-transferase 3-3 that has all three
      cysteine residues replaced with serine (CallS) and a quadruple mutant with a Tyr
      115 to phenylalanine substitution on CallS (CallSY115F) were reacted with 2-(S
      glutathionyl)-3,5,6-trichloro-1,4-benzoquinone (GS-1,4-TCBQ). The modified
      proteins were analysed on a triple-quadrupole mass spectrometer equipped with an
      electrospray ionization source. At an enzyme: GS-1,4-TCBQ ratio of 1:10, the
      enzymes were modified at multiple sites. Covalent attachment of a single
      inhibitor on to the protein was achieved by lowering the enzyme: GS-1,4-TCBQ
      ratio to 1:1. Results from m.s. analyses suggest that the inhibitor on the
      CallSY115F mutant exists as a glutathionyl dichlorobenzoquinone derivative. The
      modifiers of the CallS mutants are glutathionyl monochlorobenzoquinone
      derivatives. Therefore, GS-1,4-TCBQ reacts at a single site on CallSY115F, but
      probably cross-links two regions on wild-type and CallS mutant. To confirm our
      observation, CallS was modified with 1-chloro2,4-dinitrobenzene, which
      specifically labels Tyr-115, before reacting with GS-1,4-TCBQ. The inhibitor
      formed a glutathionyl dichlorobenzoquinone adduct on the dinitrophenyl-CallS
      mutant. In addition, the benzoquinone derivative on the protein can be partially
      removed by 1-chloro-2,4-dinitrobenzene. Peptide mapping and sequencing analysis
      of the GS-1,4-TCBQ-modified CallS mutant revealed that the C-terminal 16-amino
      acid fragment is labelled. Molecular modelling suggests the C(5) and C(6) on the
      benzoquinone ring of the inhibitor interact with the oxygen atoms of Tyr-115 and
      Ser-209 respectively.

PMID- 7818488
TI  - The gene family of EF-hand calcium-binding proteins from the flagellum of
      Trypanosoma brucei.
AB  - The flagellum of Trypanosoma brucei contains calmodulin, and a separate family of
      antigenically related EF-hand calcium-binding proteins which we call calflagins.
      The following study evaluates the structure and genomic organization of the
      calflagin family. Genomic Southern blots indicated that multiple copies of
      calflagin genes occurred in T. brucei, and that all of these copies were
      contained in a single 23 kb XhoI-XhoI fragment on chromosomes 15 and 16 mRNAs of
      1.2 and 1.6 kb were identified in bloodstream and procyclic life-cycle stages.
      Genomic fragments of 2.5 and 1.7 kb were cloned that encoded calflagin sequences.
      The calflagin genes were arranged tandemly along the genomic fragments. Three new
      members of the calflagin family were sequenced from a cDNA clone and the two
      genomic clones. Two unrelated families of 3' flanking sequences were downstream
      from the calflagin genes. An open reading frame that was unrelated to any
      calflagin sequence was at the 5' end of the 2.5 kb genomic fragment. The deduced
      amino acid sequences of the genomic clones (called Tb-24 and Tb-1.7g) were
      similar to the previously described Tb-17. Each encoded an approximately 24 kDa
      protein which contained three EF-hand calcium-binding motifs and one degenerate
      EF-hand motif. The cDNA encoded a protein (called Tb-44A) which was approximately
      twice as large as the other calflagins. The large size resulted from a nearly
      direct repeat of 186 amino acids. In general, variability among the T. brucei
      calflagins was greater than observed for related proteins from Trypanosoma cruzi.
      We demonstrate that this variability resulted from amino acid substitutions at
      the N-terminus, C-terminal extensions, and duplication of internal segments.

PMID- 7818489
TI  - Variability of glutathione S-transferase isoenzyme patterns in matched normal and
      cancer human breast tissue.
AB  - The determination of GST levels in blood has been proposed to a marker of tumour
      burden in general, whereas level of the P1 isoenzyme has been identified as a
      prognostic factor for breast-cancer patients receiving no adjuvant chemotherapy.
      Particular glutathione S-transferase (GST) isoenzymes differ in their substrate
      specificity, however, and their presence or absence might therefore account for
      the resistance of tumours to particular chemotherapeutic drugs, as already
      established for cultured cell lines. Determination of the GST isoenzyme profile
      of a cancer tissue could have prognostic value in the selection of treatment if
      the levels of expression/activity show a degree of variation comparable with that
      exhibited by actual patient responses. Using reversed-phase h.p.l.c. to quantify
      affinity-isolated GSTs, we have analysed full isoenzyme profiles in the first
      large sample of matched normal and cancer human tissues (18 breast-cancer
      patients). In no patients did the tumour tissues express any isoenzymes that were
      not found in normal breast tissue. In addition to the GSTs, another enzyme,
      identified as enoyl-CoA isomerase, was regularly found in breast tissue cytosol
      following elution from a hexyl-glutathione affinity column. In most cases, the
      average level of GST was substantially elevated in the cancer tissues above the
      levels in normal breast tissue from the same patient. Furthermore, the relative
      levels of the isoenzymes were substantially more variable in the cancer samples
      than in the normal breast tissue, providing a plausible mechanism for the well
      established variable response to treatment.

PMID- 7818490
TI  - Delta 3, delta 2-enoyl-CoA isomerase is the protein that copurifies with human
      glutathione S-transferases from S-hexylglutathione affinity matrices.
AB  - An unidentified 30 kDa protein frequently copurifies with human glutathione S
      transferases from S-hexyl-glutathione affinity matrices. Application of two-step
      sequential affinity chromatographic methods yielded a homogeneous preparation of
      that protein from human liver specimens. The protein was digested with
      Achromobacter protease I, and sequences of peptides resolved by h.p.l.c. showed a
      high degree of identity with those of rat mitochondrial delta 3, delta 2-enoyl
      CoA isomerase. The human protein also exhibited catalytic activity with delta 3
      cis-octenyl CoA as a substrate. Thus it is identified as liver delta 3, delta 2
      enoyl-CoA isomerase.

PMID- 7818491
TI  - Recombinant glycosyl-phosphatidylinositol-anchored proteins are not associated
      with protein kinases in transfected thymoma cells.
AB  - The cross-linking by antibody of some glycosyl-phosphatidyl-inositol (GPI)
      anchored proteins on the plasma membrane of T cells leads to cell activation.
      Phosphorylation of proteins on tyrosine residues has a central role in the
      control of T cell activation, and non-receptor protein tyrosine kinases can be
      coprecipitated with immune complexes of GPI-anchored proteins in T cell lysates.
      In order to investigate the nature of this interaction, two recombinant GPI
      anchored proteins were constructed (using the GPI signal sequence from Thy-1),
      and their associations with protein tyrosine kinases in stable transfectants of a
      mouse thymoma have been investigated. One recombinant GPI protein is the
      extracellular domain of the human complement receptor-1, normally an integral
      membrane protein, and the other is the secreted protein, human tissue inhibitor
      of metalloproteinases. The latter protein should be foreign to the cell surface
      and yet has been expressed as a GPI-anchored protein at levels equivalent to the
      highly expressed antigens Thy-1 and Ly6.A2 on mouse thymoma cells. Neither of the
      two recombinant proteins, when immunoprecipitated from NP40 lysates of
      transfected cells, was associated with protein tyrosine kinases in contrast with
      the natural endogenous GPI-anchored proteins Thy-1 and Ly6.A2 in non-transfected
      parental cells. Moreover, high expression of foreign recombinant GPI protein
      appears to interfere with the association of the natural GPI proteins with
      protein tyrosine kinases.

PMID- 7818492
TI  - Characterization of a thioredoxin-related surface protein.
AB  - A surface-associated sulphydryl (thiol) protein (SASP) constitutively present in
      most nucleated cells was purified from human THP-1 monocytes and rat C6 glioma
      cells. The human protein was similar in mass and isoelectric point and had the
      same N-terminal amino acid sequence to adult T-cell leukemia-derived factor
      (ADF), a growth factor secreted by human lymphoid cells which is able to induce
      increased expression of interleukin-2 receptors. A further internal amino acid
      sequence, determined following cleavage of human SASP with cyanogen bromide, was
      also identical to the corresponding sequence deduced for ADF. Samples of SASP
      were able to reductively depolymerize human immunoglobulin, a property shared
      with thioredoxin, a ubiquitous protein, almost identical to ADF, with an
      essential function in many thiol-dependent reducing reactions. Furthermore, SASP
      purified from rat C6 glioma cells had an identical N-terminal amino acid sequence
      to that deduced for rat liver thioredoxin, showing that they were both members of
      the same family of proteins. The use of membrane-impermeable thiol reagents
      indicated that SASP was predominantly a cell-surface protein, and was not
      normally secreted. This SASP protein appeared to be a surface-associated form of
      thioredoxin that was constitutively present in a wide range of cells and was
      related to ADF, a secreted form of the same protein.

PMID- 7818493
TI  - gamma-Glutamyltranspeptidase-catalysed acyl-transfer to the added acceptor does
      not proceed via the ping-pong mechanism.
AB  - Acyl-transfer catalysed by gamma-glutamyltranspeptidase from bovine kidney was
      studied using gamma-L- and gamma-D-Glu-p-nitroanilide as the donor and GlyGly as
      the acceptor. The transfer of the gamma-Glu group to GlyGly was shown to be
      accompanied by transfer of the gamma-Glu group to water (hydrolysis). The results
      were compared with acyl-transfer catalysed by the representative serine protease,
      alpha-chymotrypsin. The main difference between the kinetic mechanism of the acyl
      transfer reactions catalysed by these enzymes, which contain an active-site
      serine and form an acyl-enzyme intermediate but belong to different enzyme
      classes, was found to consist in the role of the enzyme-donor-acceptor complex.
      This complex is not formed at any acceptor concentrations in the acyl-transfer
      reactions catalysed by the serine proteases. In contrast, in the gamma
      glutamyltranspeptidase-catalysed acyl-transfer the pathway going through the
      ternary enzyme-donor-acceptor complex formed from the enzyme-acceptor complex
      becomes the main pathway of the transfer reaction even at moderate acceptor
      concentrations. As a result, gamma-glutamyltranspeptidase catalysis follows a
      sequential mechanism with random equilibrium addition of the substrates and
      ordered release of the products. The second distinction concerns the inhibitory
      effect of the acceptor. In the case of alpha-chymotrypsin this was the result of
      true inhibition, i.e. a dead-end formation of the enzyme-acceptor complex. A salt
      effect caused by the acceptor was the rationale of a similar effect observed in
      acyl-transfer catalysed by gamma-glutamyltranspeptidase.

PMID- 7818495
TI  - Proteoglycans isolated from dissociative extracts of differently aged human
      articular cartilage: characterization of naturally occurring hyaluronan-binding
      fragments of aggrecan.
AB  - Proteoglycans extracted with 4 M guanidinium chloride from young (mean 20 years)
      or old (mean 79 years) macroscopically normal human articular cartilage were
      separated by density gradient centrifugation and Q-Sepharose chromatography and
      characterized by gradient gel SDS/PAGE and immunodetection before and after
      removal of glycosaminoglycan chains. The extracts contained two large populations
      of aggrecan, a population of small N-terminal aggrecan fragments, as well as
      decorin, biglycan and fibromodulin. The distribution of all these species in
      density gradient fractions has been determined. The large aggrecan populations
      comprised four different chondroitin sulphate-bearing core proteins while the
      population of smaller fragments comprised eight different components. The two
      smallest fragments (35 and 42 kDa), identified as the first globular domain of
      aggrecan (N-terminal) (G1) and containing no glycosaminoglycan, were detected
      only in extracts of old cartilage. A 55 and a 70 kDa fragment of G1 were present
      in both keratan sulphate-containing and non-keratan sulphate-containing forms.
      Four other fragments, each containing keratan sulphate epitopes, were identified
      and these contained either G1 epitopes (one 95 kDa species), or G1 and G2
      epitopes (three species). These results have suggested that proteolytic
      processing at the N-terminus is more extensive than has previously been
      recognized and raises the possibility that more than one proteinase may be
      involved in aggrecan degradation in vivo. With the exception of the two smallest
      G1 fragments, the repertoire of proteoglycan fragments found in young and old
      human articular cartilage is essentially the same, although the relative
      abudnance of various species differed. The older tissue contains a larger
      proportion of C-terminally truncated aggrecan fragments and a significantly
      decreased content of decorin and biglycan.

PMID- 7818494
TI  - Adenosine stimulates DNA fragmentation in human thymocytes by Ca(2+)-mediated
      mechanisms.
AB  - Incubation of human thymocytes with an optimum concentration of adenosine and its
      receptor site agonist, 2-chloroadenosine, induced increases in intracellular
      cyclic AMP (cAMP) (from a resting 0.6 +/- 0.1 to 4.1 +/- 0.2 pmol/10(7) cells
      within 5 min) and Ca2+ (from the resting 85 +/- 7 nM to a peak of 210 +/- 25 nM)
      levels and resulted in internucleosomal DNA fragmentation and cell death
      (apoptosis). Other adenosine analogues were also effective at inducing DNA
      fragmentation, the order of potency being 2-p-(carboxyethylphenylethylamino)-5'
      carboxyamidoadenosine < 5'-(N-ethylcarboxamide)adenosine < or =
      cyclopentyladenosine < 2-chloroadenosine (2-CA). 2-CA treatment (with an optimum
      concentration of 40 microM) selectively depleted a thymocyte subpopulation (15
      20% of the total cells) which expressed higher levels of the CD3 molecule and
      which was found mainly in the CD4+CD8+ double positive immature thymocyte
      population. DNA fragmentation was prevented by the addition of actinomycin D or
      cycloheximide to the thymocyte suspension, indicating that this process required
      both mRNA and protein synthesis. Endonuclease activation and cell killing were
      dependent on an early, sustained increase in cytosolic Ca2+ concentration, most
      of which was of extracellular origin and was a result of an adenosine-induced
      inositol trisphosphate release. Other agents known to elevate intracellular cAMP
      levels by different mechanisms failed to induce similar DNA fragmentation, but
      enhanced the effect of adenosine. This suggested a supporting role for cAMP in
      adenosine-induced DNA fragmentation. Phorbol dibutyrate, a protein kinase. C
      activator, previously shown to inhibit Ca(2+)-dependent DNA fragmentation and
      cell killing in human thymocytes [McConkey, Hartzell, Jondal and Orrenius (1989)
      J. Biol. Chem. 264, 13399-13402], at 60 ng/ml concentration also prevented
      adenosine-induced DNA fragmentation when added prior to adenosine. This suggested
      a complex cross-talk between the adenosine-triggered signal transduction cascade
      and the activation state of protein kinase C in regulating apoptosis of human
      thymocytes.

PMID- 7818496
TI  - Effect of enzymic methylation of heterogeneous ribonucleoprotein particle A1 on
      its nucleic-acid binding and controlled proteolysis.
AB  - Recombinant unmethylated heterogeneous nuclear ribonucleoprotein particle (hnRNP)
      protein A1 was enzymatically methylated by nuclear protein/histone protein
      methylase I [Rajpurohit, Lee, Park, Paik and Kim (1994) J. Biol. Chem. 269, 1057
      1082] and the effect of methylation on several physiocochemical properties was
      studied. The relative binding-affinity of methylated and unmethylated protein A1
      to nucleic acid was quite different. This was observed by the elution behaviour
      of the protein A1 on a single-stranded DNA/cellulose column; the concentration of
      NaCl required to release the bound protein A1 was 0.59 M for the methylated and
      0.63 M for the unmethylated, respectively. Employing isoelectrofocusing, pI
      values of the methylated and unmethylated proteins were found to be 9.41 and
      9.48, respectively. Maximum fluorescence quenching of protein A1 in the presence
      of coliphage MS2-RNA was found to be 40% with methylated and 45% with
      unmethylated. When both species of protein A1 were subjected to controlled
      trypsin digestion, t1/2 of the methylated protein was 1.31 min and the
      unmethylated, 1.63 min. The difference in their t1/2 values was much greater in
      the presence of MS2-RNA; 2.4 min for the former and 4.3 min for the latter,
      indicating that the methylated species was less stabilized by the RNA than the
      unmethylated. All of the above results consistently suggested that the binding
      property of hnRNP protein A1 to single-stranded nucleic acid was significantly
      reduced subsequent to its arginine-methylation. The biological significance of
      this observation is discussed.

PMID- 7818497
TI  - Identification and partial sequence analysis of novel annexins in Lytechinus
      pictus oocytes.
AB  - The annexins are a major class of calcium-binding proteins with unknown
      functions. In an attempt to define novel model systems in which to study members
      of the annexin family, we have investigated the expression of annexins in eggs
      from the sea urchin Lytechinus pictus. Western blot analysis of L. pictus eggs
      using antisera raised against human annexins I, V and VI revealed the presence of
      immunoreactive proteins of approximately 34 kDa, 35 kDa and 68 kDa respectively.
      The sea urchin annexins behaved similarly to their mammalian counterparts, both
      during purification and in their ability to bind calcium-dependently to anionic
      phospholipids. Of the three sea urchin annexins, the 34 kDa form was most
      abundant, yielding sufficient quantities for peptide microsequencing. The amino
      acid sequences derived in this way showed the L. pictus annexin to be closely
      related both to mammalian annexin I and to annexins IX, X and XII from Drosophila
      and Hydra. However, N-terminal sequence from the L. pictus annexin showed it to
      be a novel member of the annexin super-gene family. The results are interesting
      in view of the complex evolution of the annexin gene family, and also point to
      the potential usefulness of echinoderm eggs as a model system in which to study
      annexin function.

PMID- 7818498
TI  - Selective elongation of the oligosaccharide attached to the second potential
      glycosylation site of yeast exoglucanase: effects on the activity and properties
      of the enzyme.
AB  - Three exoglucanases (Exgs), ExgIa, ExgIb and Exg325, are secreted by
      Saccharomyces cerevisiae cells. They share a common protein portion with two
      potential glycosylation sites (sequons) but differ in the amount of N-linked
      carbohydrate [Basco, R.D., Munoz, M.D., Hernandez, L.M., Vaquez de Aldana, C. and
      Larriba, G. (1993) Yeast 9, 221-234]. ExgIb contains two short oligosaccharides
      attached to asparagines (Asn) 165 and 325 of the primary translation product
      [Hernandez, L.M., Olivero, I., Alvarado, E. and Larriba, G. (1992) Biochemistry
      31, 9823-9831]. Exg325 carries a single, short oligosaccharide bound to Asn325
      whereas ExgIa has at least one large oligosaccharide, since it has not been
      produced by mutant mnn9. To address the question of the origin of ExgIa, both
      sequons were individually mutated by substituting Gln for Asn. An ExgIa-like
      isoenzyme was still secreted by mutant Exg165 but not by mutant Exg325.
      Additional studies on sequential deglycosylation of ExgIa with endo-beta-N
      acetylglucosaminidase H (endo H), the susceptibility of both oligosaccharides to
      the endoglycosidase, and analysis of the presence of GlcNAc at both asparagine
      residues after total deglycosylation with endo H, indicated that ExgIa contained
      two oligosaccharides, a short one bound to Asn165 and a large one bound to
      Asn325, and, accordingly, originated from ExgIb. The elongation of the second
      oligosaccharide did not result in a higher stability towards thermal inactivation
      or unfolding, or in an increased resistance to proteases as compared with ExgIb;
      however, the affinity of the enzyme towards laminarin decreased by 50%. This site
      specific elongation occurred in the oligosaccharide that was less susceptible to
      endo H, indicating that these properties are determined by different
      conformational constraints.

PMID- 7818500
TI  - Purification and characterization of the short-chain alkylsulphatase of
      coryneform B1a.
AB  - Using a combination of streptomycin sulphate precipitation, and DEAE-cellulose
      and butyl-agarose chromatography, an alkylsulphatase active towards short-chain
      alkyl sulphates has been purified approx. 70-fold from extracts of coryneform B1a
      grown on butyl-1-sulphate. The enzyme protein is dimeric with a subunit molecular
      mass of 77.6 kDa, has an isoelectric point of pI 7.2, and converts butyl-1
      sulphate stoichiometrically into butan-1-ol and inorganic sulphate.
      Stoichiometric incorporation of 18O from H2(18)O into sulphate during the
      reaction showed that enzymic hydrolysis occurred at the O-S bond of the C-O-S
      ester linkage. The enzyme was active on C3-C7 linear primary alkyl sulphates but
      not on higher (C8,9) or lower (C1,2) homologues, although the latter pair were
      competitive inhibitors. The specificity constant (kcat./Km) was highest for
      pentyl sulphate (Km 1.89 +/- 0.38 mM; kcat. 6.86 +/- 0.52 s-1) and decreased for
      higher and lower homologues. No activity was detected towards C3-C9 racemic alkyl
      2-sulphates, D- or L-enantiomers of butyl-2-sulphate, the symmetrical secondary
      alkyl sulphates pentyl-3-sulphate, heptyl-4-sulphate, nonyl-5-sulphate, C1-C8
      alkane sulphonates, choline sulphate, or butyric acid-4-sulphate; none of these
      compounds (except the symmetrical esters and butyric acid-4-sulphate, which were
      not tested) was demonstrably inhibitory. The enzyme was compared with other
      alkylsulphatases in terms of substrate specificity and mode of action.

PMID- 7818501
TI  - Determination of the mechanism of reaction for bile acid: CoA ligase.
AB  - The reaction of cholic acid, CoA and ATP to yield cholyl-CoA was investigated by
      kinetic analysis of the reaction as catalysed by guinea pig liver microsomes. The
      enzyme has an absolute requirement for divalent cation for activity so all
      kinetic analyses were carried out in excess Mn2+. A trisubstrate kinetic analysis
      was conducted by varying, one at a time ATP cholate and CoA. Both ATP and cholate
      gave parallel double reciprocal plots versus CoA, which indicates a ping-pong
      mechanism with either pyrophosphate or AMP leaving prior to the binding of CoA.
      Addition of pyrophosphate to the assays changed the parallel plots to
      intersecting ones; addition of AMP did not. This indicates that pyrophosphate is
      the first product. The end-product, AMP, was a competitive inhibitor versus ATP,
      as was cholyl-CoA at saturating concentrations of cholate. Both AMP and cholyl
      CoA were uncompetitive inhibitors versus CoA. Based on this information, it was
      concluded that the reaction follows a bi uni uni bi ping-pong mechanism with ATP
      binding first, and with the release of the final products, AMP and cholyl-CoA,
      being random. CoA showed substrate inhibition at high but non-saturating
      concentrations and this inhibition was competitive versus ATP, which is
      consistent with the predicted ping-pong mechanism. The ability of cholyl-CoA, but
      not cholate or CoA, to bind with high affinity to the free enzyme was suggestive
      of a high affinity of the enzyme for the thioester link.

PMID- 7818499
TI  - Phosphorylation and activation of Ca(2+)-sensitive cytosolic phospholipase A2 in
      MCII mast cells mediated by high-affinity Fc receptor for IgE.
AB  - In the present study we examined the activation of Ca(2+)-sensitive cytosolic
      phospholipase A2 (cPLA2) after aggregation of cell-surface high-affinity Fc
      receptors for IgE (Fc epsilon RI) on mast cells. MCII mast cells (a factor
      dependent bone-marrow-derived murine mast cell line) produce significant amounts
      of leukotriene C4 (LTC4) (70 ng/10(6) cells) on cross-linking of Fc epsilon RI.
      Using enzymic and immunochemical analysis we found that cPLA2 is the predominant
      form of this enzyme in MCII mast cells (0.2 micrograms/mg of total protein) and
      other forms (i.e. secretory PLA2 or Ca2+ independent cytosolic PLA2) could not be
      detected. Therefore MCII mast cells represent an excellent cellular model for the
      study of the biochemical mechanism(s) responsible for Fc epsilon RI-induced
      activation of cPLA2 and the involvement of cPLA2 in Fc epsilon RI-mediated
      production of LTC4. After activation of Fc epsilon RI by cross-linking, cPLA2 in
      MCII mast cells exhibited a decreased electrophoretic mobility and its enzyme
      activity was increased 3-fold. Treatment with phosphatase reversed both the
      altered electrophoretic mobility and the enhanced enzyme activity demonstrating
      that they were the result of Fc epsilon RI-induced phosphorylation. On cross
      linking of Fc epsilon RI, cPLA2 was phosphorylated within 30 s and appeared to be
      an early substrate for Fc epsilon RI-activated protein kinases in MCII mast
      cells. Tyrosine phosphorylation may be a critical component in this process, as
      genistein, an inhibitor of protein tyrosine kinases, blocked the activation of
      cPLA2. Using anti-phosphotyrosine antibodies we observed that the activating
      phosphorylation was not on tyrosine residues of cPLA2, indicating that tyrosine
      kinases participate upstream in the signalling cascade that couples Fc epsilon RI
      to cPLA2. We conclude that in MCII mast cells cPLA2 is activated by kinase
      dependent mechanisms and may be responsible for Fc epsilon RI-induced
      mobilization of arachidonic acid for the generation of LTC4.

PMID- 7818502
TI  - Solubilization and characterization of diacylglycerol acyltransferase from
      microspore-derived cultures of oilseed rape.
AB  - Particulate fractions prepared from microspore-derived (MD) embryos of oilseed
      rape (Brassica napus L. cv. Reston) and an embryogenic MD cell suspension culture
      of oilseed rape (B. napus L. cv. Jet Neuf) were used as a source of
      diacylglycerol acyltransferase (DGAT, EC 2.3.1.20) for enzyme characterization
      and development of a solubilization procedure. DGAT activity in the 1500-100,000
      g fraction from MD embryos was stimulated 4-5-fold by 3 to 4 mg of BSA/ml of
      reaction mixture. DGAT activity from MD embryos was stimulated 2-3-fold by
      fluoride salts and 1.4-fold by NaCl, whereas iodide salts caused substantial
      inhibition of enzyme activity. The effect of the various 1:1 electrolytes on
      enzyme activity appeared to be related more to their differential effects on
      solution structure rather than ionic strength. DGAT was solubilized from
      membranes of MD embryos and the cell suspension culture by about 80 and 50%
      respectively, using 2 M NaCl in 1% (w/v) octanoyl-N-methyl-glucamide (MEGA-8) (pH
      8.0 buffer) at a detergent to protein ratio of 2:1. The specific activity of
      solubilized DGAT was about 2-fold greater than that of the particulate enzyme.
      The mechanism of solubilization appeared to be related to the lowering of the
      critical micellar concentration of MEGA-8 in the presence of NaCl. DGAT,
      solubilized from MD embryos, eluted with an M(r) of about 2 x 10(6) during gel
      filtration chromatography on a Superose 6 column equilibrated in buffer
      containing 0.1% (w/v) MEGA-8. The solubilized enzyme exhibited optimal activity
      at pH 7. At concentrations above 2 microM acyl-CoA, the specificity of
      solubilized DGAT for oleoyl-CoA and palmitoyl-CoA was considerably greater than
      for stearoyl-CoA.

PMID- 7818503
TI  - Effect of protamine on lipoprotein lipase and hepatic lipase in rats.
AB  - The polycation protamine impedes the catabolism of triglyceride-rich lipoproteins
      and this has been suggested to be due to intravascular inactivation of
      lipoprotein lipase. We have made intravenous injections of protamine to rats and
      found that both lipoprotein lipase and hepatic lipase activities were released to
      plasma. The effect of protamine was more short-lived than that obtained by
      injection of heparin. The release of hepatic lipase by protamine was as effective
      as the release by heparin, while the amount of lipoprotein lipase released by
      protamine was only about one-tenth of that released by heparin. This was not due
      to inactivation of lipoprotein lipase, since injection of an excess of heparin 10
      min after injection of protamine released as much lipoprotein lipase activity to
      plasma as in controls. The results in vivo differed from those obtained in model
      experiments in vitro. Protamine was able to almost quantitatively release both
      lipoprotein lipase and hepatic lipase from columns of heparin-agarose. The
      displacement was dependent on the total amount of protamine that had passed over
      the column, indicating that it was due to occupation by protamine of all
      available binding sites. Our results in vivo showed that the binding sites for
      lipoprotein lipase were not blocked as efficiently as those for hepatic lipase,
      indicating that the binding structures were not identical. It was concluded that
      the impaired turnover of lipoproteins by protamine probably was due to prevention
      of binding of the lipoproteins to endothelial cell surfaces rather than to
      impaired lipase function.

PMID- 7818504
TI  - Binding of quinomycin antibiotic UK-65,662 to DNA: 1H-n.m.r. studies of drug
      induced changes in DNA conformation in complexes with d(ACGT)2 and d(GACGTC)2.
AB  - Quinomycin antibiotic UK-65,662 binds selectively to the 5'-CpG-binding sites of
      the DNA duplexes d(ACGT)2 and d(GACGTC)2; the complexes have been studied in
      detail by 1H-n.m.r. spectroscopy and molecular-modelling techniques employing
      nuclear Overhauser effect-restrained energy minimization and molecular dynamics.
      Whereas the terminal A.T base pairs of the tetamer duplex d(ACGT)2 adopt a stable
      Hoogsteen alignment (characterized by a syn glycosidic conformation of the purine
      base), when internalized within the hexamer duplex d(GACGTC)2, the A.T base pairs
      revert to anti glycosidic torsion angles characteristic of the Watson-Crick
      hydrogen-bonding scheme. The energetics of base-pair stacking at the terminal 5'
      GpA steps of the hexamer complex, with base pairs in the Watson-Crick alignment,
      are concluded to be important determinants of the adopted conformation, whereas
      an energetic preference for stacking interactions between terminal Hoogsteen A.T
      base pairs and the drug quinoline chromophores is evident in the tetramer
      complex. The internal G.C base pairs in both complexes are highly stabilized, as
      indicated by the very slow exchange rates of the guanine imino protons; in
      contrast, the flanking A.T base pairs are no more stable than in the ligand-free
      DNA duplexes. A large number of intermolecular nuclear Overhauser effects are
      indicative of many van der Waals contacts and hydrogen-bonding between the
      antibiotic and the minor groove of the central G.C base pairs in both complexes,
      indicating that interactions with the G.C base pairs in each duplex are very
      similar providing the essential features for recognition and tight binding.
      Despite the difference in the conformation of the A.T base pairs, stacking with
      the quinoline rings occurs primarily with the adenine bases in both complexes.
      Relative intensities of intranucleotide versus internucleotide nuclear Overhauser
      effects indicate that both duplexes are substantially unwound by drug binding
      (particularly at the CpG step) and this is confirmed by the structure
      calculations. Both duplexes have ladder-like structures that must lead to
      significant local distortions of the DNA conformation in vivo.

PMID- 7818505
TI  - Purification and characterization of thyroid transcription factor 2.
AB  - Thyroid transcription factor 2 binds to the promoters of both thyroglobulin and
      thyroperoxidase genes, two markers of thyroid tissue differentiation, and its
      binding modulates the activity of both promoters. In this paper we describe the
      purification of thyroid transcription factor 2 essentially to homogeneity and
      demonstrate that it is a thyroid-specific DNA-binding protein. Furthermore, we
      provide a biochemical characterization suggesting that thyroid transcription
      factor 2 binds to DNA as a dimer and that it is a zinc-finger DNA-binding protein
      regulated in vitro by the redox state.

PMID- 7818506
TI  - Homogeneous pyrimidine nucleotidase from human erythrocytes: enzymic and
      molecular properties.
AB  - A pyrimidine nucleotidase with unique specificity has been obtained for the first
      time as an homogeneous protein from the cytosolic fraction of human erythrocytes.
      Both conventional chromatography and f.p.l.c. techniques have been used in the
      purification procedure. The final enzyme preparation gave a single protein band
      of M(r) = 23,500 on SDS/PAGE under both reducing and non-reducing conditions. The
      native enzyme was eluted at M(r) = 45,000 in gel filtration chromatography on
      Superose 12, suggesting a dimeric structure. Amino acid analysis was consistent
      with an acidic isoelectric point and revealed the presence of six half-cystine
      and two methionine residues per subunit. The enzyme was active on a variety of
      pyrimidine nucleoside monophosphates, being most active on the 3'-monophosphates.
      Km values for 3'dUMP, 3'UMP, 5'dUMP, 5'UMP, 5-fluoro-2'dUMP, ranged from 192
      microM to 1.15 mM. The enzyme activity was inhibited by both reaction products,
      orthophosphate, and the nucleoside formed. Product inhibition studies suggested
      an Ordered Uni-Bi mechanism for the reaction. The enzyme required Mg2+ for its
      activity, while heavy metals cations were strongly inhibitory. The enzyme
      activity was inhibited by metal chelating agents and it was sensitive to
      thioreactive reagents. The isoelectric point was 5.4 and the optimum activity pH
      was 6.5.

PMID- 7818507
TI  - Receptor occupancy regulates Ca2+ entry and intracellular Ca2+ redistribution in
      activated human platelets.
AB  - Fura-2-loaded human platelets were used to study Ca2+ release from intracellular
      compartments, as well as Ca2+ influx from the extracellular space. We
      investigated the response towards the endoperoxide/thromboxane-receptor agonist.
      U46619, and the inhibitor of the endoplasmic-reticulum Ca(2+)-ATPase,
      thapsigargin. U46619 dose-dependently depleted intracellular Ca2+ stores,
      followed by active sequestration of released Ca2+. Ca2+ influx induced by U46619
      largely relies on receptor occupancy. Removing the thromboxane analogue from its
      receptor by using the endoperoxide/thromboxane-receptor antagonist BM 13177
      largely blunted U46619-mediated Ca2+ influx. The Ca(2+)-ATPase inhibitor
      thapsigargin evoked a gradual rise in intracellular Ca2+, which was potentiated
      by a preceding activation of platelets with the receptor agonist U46619. This
      agonist-sensitizing effect also depends on receptor occupancy. Removing U46619
      from its receptor by addition of the endoperoxide/thromboxane-receptor antagonist
      BM13177 suppressed the sensitizing effect completely. Furthermore, interrupting
      downstream receptor signalling events by raising intracellular levels of cyclic
      nucleotides (cyclic AMP, cyclic GMP) again suppressed the U46619-sensitizing
      effect on thapsigargin-induced Ca2+ release. This study indicates that the
      process of Ca2+ release followed by resequestration in response to a platelet
      agonist by its own is not sufficient to produce the sensitizing effect. Rather, a
      continuously occupied receptor triggering sustained downstream signalling events
      seems to be required for sensitization. The presence of a receptor agonist may
      induce an increased cycling of Ca2+ between the agonist-responsive and the
      thapsigargin-dischargeable compartment, leading to faster and more intense
      accumulation of Ca2+ in the cytosolic compartment after inhibition of the Ca(2+)
      ATPase. Suggestively, receptor occupancy increases the Ca(2+)-releasing potency
      of thapsigargin by coupling the thapsigargin-sensitive Ca(2+)-storing
      compartments with an agonist-responsive compartment that exhibits a high leakage
      rate in stimulated platelets.

PMID- 7818508
TI  - Anti-syntaxin antibodies inhibit calcium-dependent catecholamine secretion from
      permeabilized chromaffin cells.
AB  - Adrenomedullary chromaffin cells release catecholamines in response to the
      intracellular calcium rise upon stimulation by different secretagogues. The
      presence of syntaxin 1, a protein presumably involved in docking of synaptic
      vesicles to presynaptic membranes, has been investigated in chromaffin cells. The
      study using two different monoclonal antibodies shows that syntaxin 1 is present
      in the chromaffin cell membrane fraction. Functional experiments demonstrate that
      anti-syntaxin antibodies inhibit calcium-dependent secretion in permeabilized
      cells. These results suggest that syntaxin 1 is an important component of the
      secretory machinery in chromaffin cells.

PMID- 7818509
TI  - Enhancement of the expression of the alpha 2-adrenoreceptor protein and mRNA by a
      direct effect of androgens in white adipocytes.
AB  - In vivo, testosterone-treatment of female hamsters for 4 days promotes a doubling
      of alpha 2-adrenoreceptor protein in parametrial adipocytes, with a concomitant
      accumulation of the alpha 2A-adrenoreceptor subtype mRNA. During in vitro
      incubation of minced parametrial fat pads for 6 to 48h with testosterone or
      dihydrotestosterone (100 nM), alpha 2A-adrenoreceptor protein and mRNA levels
      were also increased and remained to control levels when an antiandrogen or
      actinomycin D were added in the medium. It is concluded that in hamster
      adipocytes, androgens upregulate alpha 2A-adrenoreceptor subtype expression at
      the mRNA level by an androgen receptor-dependent transcriptional activation.

PMID- 7818510
TI  - The specific bisindolylmaleimide PKC-inhibitor GF 109203X efficiently modulates
      MRP-associated multiple drug resistance.
AB  - The newly identified drug transporter MRP is functionally linked to a multiple
      drug resistance independent from P-glycoprotein. Resistance modifiers for this
      type of MDR are rare at present. We analyzed the modulating effect of the highly
      selective bisindolylmaleimide PKC inhibitor GF 109203X on the MRP overexpressing
      human MDR sublines HL60/AR and GLC4/ADR. Applying a 72 hour MTT-assay we
      demonstrate a complete reversal of the vincristine resistance of HL60/AR cells.
      Adriamycin resistance of HL60/AR, or vincristine resistance of GLC4/ADR were
      partially reversed. Furthermore, rhodamine 123 efflux from HL60/AR was strongly
      modulated by GF 109203X. Since the PKC inhibitor did not significantly influence
      MRP gene expression at the mRNA level which was examined by cDNA-PCR, our results
      suggest either a direct interaction of the compound with MRP or/and an indirect
      influence on MRP activity via altering the phosphorylation status of the
      transporter.

PMID- 7818511
TI  - Importance of the C-terminal part of actin in interactions with calponin.
AB  - Native, modified or trypsin-truncated actin was used to study the impact of
      modifying the C-terminal part of actin (the last three amino acids) on
      interactions with calponin. We used three different techniques to show that these
      amino acids are essential for the actin-calponin interface. The locations of
      actin-calponin interaction sites on the actin crystal are discussed in terms of
      previously reported data.

PMID- 7818513
TI  - Induction of protein oxidation in human low density lipoprotein by the
      photosensitive organic hydroperoxide, N,N'-bis(2-hydroxyperoxy-2-methoxyethyl)
      1,4,5,8-naphthalene-tetra-carb oxylic- diimide.
AB  - We have developed a new molecular probe, N,N'-bis(2-hydroxyperoxy-2
      methyoxyethyl)-1,4,5,8-naphthalen e-tetra-carboxylic- diimide (NP-III), that
      specifically generates hydroxyl radical upon irradiation with longer wavelength
      ultraviolet light (UVA). Hydroxyl radicals are generated only upon irradiation,
      thus NP-III is a new controllable hydroxyl radical source. Apolipoprotein (apo-B)
      of human low density lipoprotein (LDL), and bovine serum alubumin (BSA), were
      irradiated with UVA in the presence of NP-III and their oxidation was evaluated
      by two independent methods: assay of protein carbonyl groups and gel
      electrophoresis. NP-III oxidized apo-B and BSA in a time- and concentration
      dependent manner. The results demonstrate that NP-III is a controllable, precise,
      and potentially tagetable source of hydroxyl radicals with which to induce
      protein oxidation.

PMID- 7818512
TI  - Mechanism for a new antitumor vanadium complex: hydroxyl radical-dependent DNA
      cleavage by 1,10-phenanthroline-vanadyl complex in the presence of hydrogen
      peroxide.
AB  - Among vanadium complexes which show inhibition of cell growth for human
      nasopharyngeal carcinoma KB cell, a newly synthesized 1:1 vanadyl-1,10
      phenanthroline complex, VO(phen)2+, was found to cleave supercoiled plasmid Col
      E1 DNA effectively when hydrogen peroxide was added. But VO2+ ion was less
      effective. Lineweaver-Burk plots of the complex binding to calf thymus DNA
      indicated that VO(phen)2+ complex has a high affinity to DNA, as supported by CD
      spectral measurements. To examine the active species for DNA cleavage by the
      complex, ESR spin trapping was performed and was found that hydroxyl radicals are
      generated in a pH-dependent manner in the VO(phen)(2+)-H2O2 system, the optimal
      pH region being 8.5-9.5. In contrast, no optimum pH was observed in VO(2+)-H2O2
      system. Thus, the VO(phen)2+ complex is proposed to bind DNA and cleave it when
      hydrogen peroxide is present.

PMID- 7818514
TI  - Induction of Ca2+ signaling and possible exocytosis in endothelial cells by a
      stable leukocyte-derived factor.
AB  - Previous studies have shown that polymorphonuclear leukocytes (PMNs) release a
      stable factor that inhibits endothelium-dependent relaxation. In the present
      studies, the effects of the factor on Ca2+ signaling and on ultrastructure of
      endothelial cells were investigated. In the cultured endothelial cells, the PMN
      derived factor induced an increase in [Ca2+]i in a pattern of oscillations. The
      frequency of the Ca2+ oscillations was less than 3 spikes/10 minutes. Removal of
      extracellular Ca2+ by perfusion with Ca(2+)-free Krebs' solution abolished the
      spikes. The results of electron microscopy showed that this factor induced an
      increase in vesicle formation on the luminal surface of the rat aortic
      endothelium. The increased vesicle formation may represent exocytosis. The
      structure of the smooth muscle cells was not changed. In conclusion, the PMN
      derived factor induces a Ca2+ influx and In conclusion, the PMN-derived factor
      induces a Ca2+ influx and possible exocytosis, suggesting that the factor may
      have other biological functions besides the inhibition of the vascular
      relaxation.

PMID- 7818515
TI  - Comparison of gene expression in normal and growth hormone receptor-deficient
      dwarf chickens reveals a novel growth hormone regulated gene.
AB  - Because of a dysfunctional growth hormone (GH) receptor there is an absence of GH
      dependent gene expression in the sex-linked dwarf chicken. Therefore, a
      comparison of mRNAs expressed in normal and dwarf chickens should lead to the
      identification of mRNAs that are regulated by GH action. We have compared gene
      expression in normal and dwarf chickens using the mRNA differential display
      technique. A combination of three anchored oligo dT primers and 15 random
      decamers were used to detect at least 75 differentially expressed mRNAs. One of
      these, designated GHRG-1, hybridizes to a 0.9 kb transcript found only in liver
      and in normal chickens shows a pattern of developmental expression which
      parallels the plasma GH profile. A GHRG-1 cDNA clone was isolated that encodes a
      120 amino acid peptide with no homology to any known gene. Sequence of the
      promoter from a genomic clone shows a region with strong similarity to the GH
      response element identified in the serine protease inhibitor gene, Spi 2.1. These
      results suggest that GHRG-1 is a novel GH regulated gene.

PMID- 7818516
TI  - Metal-induced conformational heterogeneity of transferrins: a spectroscopic study
      of indium(III) and other metal(III)-substituted transferrins.
AB  - The conformation in solution of three different metal(III)-transferrins, namely
      aluminum(III), gallium(III) and indium(III) transferrin, was investigated by
      absorption, CD, 1H NMR and 13C NMR spectroscopies. The formation of the
      respective metal-transferrin complexes and the characteristic 2:1 metal-to
      protein binding stoichiometry were unambiguously demonstrated, in all cases,
      through UV difference studies. The 13C NMR spectra of these metallotransferrins
      in the carbonyl region are very similar to one another pointing out that the
      arrangement of the synergistic anion in the binding site must be essentially the
      same. However, the CD spectra in the near UV (aromatic region) reveal the
      occurrence of significant differences between indium transferrin, on one side,
      and the other two derivatives, on the other. Also, the 1H NMR spectra exhibit a
      number of different features suggesting the occurrence of metal-induced
      conformational heterogeneity around the metal sites. Such metal-induced
      conformational heterogeneity probably affects the transferrin-receptor
      recognition process, resulting in a different metabolic fate of these metals in
      the organisms.

PMID- 7818517
TI  - Mapping the residues of protein kinase CK2 implicated in substrate recognition:
      mutagenesis of conserved basic residues in the alpha-subunit.
AB  - Six mutants of protein kinase CK2 alpha subunit in which basic residues have been
      mutated into alanines were assayed for their capability to phosphorylate the
      peptide RRRADDSDDDDD. Two mutants (R228A and R278K279R280A) behaved more or less
      as alpha wild type and one (H160,166A) was nearly inactive, hampering the
      calculation of kinetic parameters. In contrast 3 mutants (K74-77A, K79R80K83A and
      R191,195K198A) phosphorylated the peptide with reduced efficiency accounted for
      by increased Km and decreased Vmax values. By using derivatives of the
      RRRADDSDDDDD peptide in which individual aspartyl residues were variably replaced
      by alanine(s) and two peptide substrates derived from I-2 (KYRIREQESSGEEDSDL and
      RRKDLHDDEEDEEMSETADGE) it was shown that mutations in the 191-198, 74-77 and 79
      83 regions were the least detrimental whenever the acidic determinants were
      lacking at positions +1, +4/+5 and +3, respectively. These data support the
      conclusion that the basic residues present in the p+1 loop of CK2 alpha
      specifically recognize the acidic determinant adjacent to the C-terminal side of
      serine, while the specificity determinants located more down-stream are variably
      recognized by different residues of the unique basic cluster spanning between
      Lys74 and Lys83.

PMID- 7818519
TI  - Mutation in the lumenal part of the membrane domain of HMG-CoA reductase alters
      its regulated degradation.
AB  - The involvement of ER lumenal domains of HMG-CoA reductase in the regulated
      degradation process was examined. For this purpose we studied three cell lines
      expressing HMG-CoA reductase molecules with introduced functional N-glycosylation
      sites located in the linker segments between transmembrane spans 1 and 2
      (HMGal/Bins(-)), 3 and 4 (HMGal/Dins(-)) and 5 and 6 (HMGal/Fins(-)), all facing
      the ER lumen (Olender, E. H. and Simoni, R. D. (1992) J. Biol. Chem. 267, 4223
      4235. The glycosylation insertion between spons 5 and 6 (HMGal/Fins(-)) is the
      only one of these mutations which eliminates regulated degradation of the enzyme.
      The half lives of the HMGal/Fins(-) in the presence or absence of regulatory
      molecules are indistinguishable. In contrast the HMGal/Bins(-) and HMGal/Dins(-)
      mutants show a normal pattern of regulated degradation. Tunicamycin treatment of
      cells expressing the HMGal/Fins(-) mutant does not significantly alter the
      regulation defect indicating that it is the mutation per se not the glycosylation
      that alters the degradation response. These results suggest that the linker
      segments between transmembrane spans 5 and 6 (loop F) are involved in the process
      of regulated degradation of HMG-CoA reductase and that the regulated degradation
      process may occur on the lumenal side of the ER membrane.

PMID- 7818521
TI  - Transglutaminase-catalyzed polymerization of troponin in vitro.
AB  - In the presence of calcium ions, tissue transglutaminase catalyzes the
      polymerization of skeletal muscle troponin to high molecular weight insoluble
      aggregate. The specific action of transglutaminase is proved by the isolation of
      glutamyl-spermidine isopeptide derivatives. The process involves mainly the
      troponin T subunit (TnT), with formation of dimers and trimers of TnT, which were
      reactive with specific antibodies by immunoblotting. Furthermore when incubation
      is carried out in the presence of radioactive polyamines, the label is
      incorporated selectively into TnT subunits.

PMID- 7818518
TI  - Sodium-mediated cell swelling is associated with irreversible damage in isolated
      hepatocytes exposed to hypoxia or mitochondrial toxins.
AB  - Incubation of isolated rat hepatocytes under hypoxic conditions or in the
      presence of inhibitors of mitochondrial functions such as KCN or carbonylcyanide
      m-chlorophenylhydrazone (CCCP) causes an increase of intracellular Na+ content
      and cell swelling. Both these effects precede the appearance of irreversible
      damage as measured by trypan blue staining of non-vital hepatocytes. When the
      increase of cellular Na+ is prevented by substitution of NaCl in the incubation
      medium with equimolar amount of choline chloride both cell swelling and loss of
      viability are greatly reduced. Thus, we propose that osmotic stress induced by an
      uncontrolled accumulation of Na+ might be associated with the ultimate events
      precipitating irreversible membrane lesions in hepatocyte undergoing metabolic
      inhibition.

PMID- 7818520
TI  - Transcriptional regulation of phospholipase C-gamma 1 gene during muscle
      differentiation.
AB  - Phospholipase C (PLC) has been known to be a key effector protein in signal
      transduction pathway for cell proliferation and differentiation. Here, we report
      the transcriptional regulation of PLC-gamma 1 during myogenic differentiation.
      Both PLC-gamma 1 mRNA and protein levels were increased during myogenesis. The
      activity of PLC-gamma 1 was also comparable to the amount estimated by Western
      blot. Comparing promoter activities of various PLC-gamma 1 gene upstream regions
      in myoblast and myotube, the responsible region was mapped between -551 and -480.
      From these results, we conclude that the transcription of PLC-gamma 1 is
      increased by the control of GPE1 region of PLC-gamma 1 gene during myogenesis.

PMID- 7818522
TI  - The nuclear factor NF-IL6 activates human placental lactogen gene expression.
AB  - Transient transfection studies using deletion mutants of the hPL promoter
      indicate that the DNA elements for NF-IL6 responsiveness are located between -2.3
      to -1.1 kb. Subsequent transfection studies using a hPL promoter fragment
      containing the region between -1376 to -1088 bp ligated to a heterologous SV40
      CAT vector (NF-IL6/hPL-CAT) demonstrated that the NF-IL6/hPL-CAT construct is
      responsive to NF-IL6. Mobility shift assays using nuclear extracts from BeWo
      choriocarcinoma cells overexpressing NF-IL6 demonstrated specific binding of the
      extracts to a labeled oligonucleotide probe to this region of the hPL promoter.
      These studies therefore strongly suggest that the effect of IL-6 on hPL gene
      expression is mediated, at least in part, by the binding of NF-IL6 to a region of
      the hPL promoter that contains three NF-IL6 responsive elements.

PMID- 7818523
TI  - Sequence comparison and computer modelling of cardiotoxins and cobrotoxin
      isolated from Taiwan cobra.
AB  - Six cardiotoxins and one neurotoxin isolated and purified from the Taiwan cobra
      venom (Naja naja atra) possess distinct pharmacological and biochemical
      properties despite the existence of a grossly similar tertiary structure among
      these toxins, i. e., a core consisting of a series of short loops and four
      disulfide bridges. A systematic structure comparison of these major toxin
      isoforms was made by the secondary-structure predictions together with computer
      model-building based on the primary sequences and the established X-ray and NMR
      structures of one published cardiotoxin isoform and cobrotoxin. It is of interest
      to find that some defined and subtle differences can be detected upon the
      superposition of these three-dimensional polypeptide chains, which may reflect
      the intrinsic differences in the surface hydrophobicity of cardiotoxins and
      cobrotoxin as revealed by hydropathy profiles of these toxins in one of three
      major loops. The differences seem to correlate with different inhibitory
      activities exhibited by cardiotoxins in contrast to the lack of activity by
      cobrotoxin on protein kinase C (PKC).

PMID- 7818524
TI  - Effects of retinoic acid (vitamin A) on tumor necrosis factor cytolytic action.
AB  - Tumor necrosis factor (TNF) is a monokine produced primarily by macrophages. TNF
      has a number of activities including direct lysis of certain transformed cells
      and induction of antiviral activity. One of the protoypical transformed cell
      lines used for studying TNF cytolysis is murine L-929 cells. Because of the
      lysis, TNF has not been shown to have antiviral activity in these cells. Since
      retinoic acid (RA) induces a normal phenotype in the L-929 cells, we sought to
      determine if their conversion to a normal phenotype would 1) render them
      insensitive to the cytolytic effect and 2) allow for the development of an
      antiviral state. We present evidence that both the cis- and trans- forms of RA
      and to a lesser extent, the RA precursor beta-carotene, can inhibit recombinant
      human TNF cytolytic activity in mouse L-929 cells. However, blockage of the
      cytolytic activity does not allow development of an antiviral state.

PMID- 7818525
TI  - An engineered disulfide bridge in the transmembrane region of phage M13 coat
      protein stabilizes the alpha-helical dimer.
AB  - A single Cys-residue (Cys24) was introduced into the 50-amino acid major coat
      protein of M13 bacteriophage as part of a two-site substitution (Y24C-V31A)
      within the effective transmembrane (TM) segment (Tyr21 to Ile39) of the coat
      protein. Mutant Y24C-V31A was able to complete the phage life cycle and was shown
      to contain free sulfhydryls in the intact virus, as evidenced by susceptibility
      of Y24C-V31A phage to alkylation by Cys-specific 14C-iodoacetamide (14C-IAN). In
      contrast, the protein solubilized in deoxycholate micelles was resistant to 14C
      IAN modification and was virtually inert to a transition from a characteristic
      alpha-helical oligomeric state to an aggregated beta-sheet structure relative to
      WT and V31A coat proteins, as shown by circular dichroism spectroscopy and SDS
      PAGE. Reduction of mainly dimeric Y24C-V31A protein using beta-mercaptoethanol
      (beta-ME) generated monomeric species and resulted in a loss of helical
      thermostability. The overall results indicated that solubilization of Y24C-V31A
      coat protein into micelles resulted in formation of thermostable disulfide
      bridged helical dimers. The disulfide bridge is deduced to be positioned along
      the stripe of residues involved in hydrophobic packing of TM parallel helical
      dimers.

PMID- 7818526
TI  - Electroporation enhances cell membrane peroxidation and luminescence.
AB  - Electroporation is a most popular method of cell membrane permeabilization, by
      pulsed electric fields. It allows foreign molecules to enter the cell and has
      been used for many biotechnological applications, including transformation of
      mammalian cells and plant protoplasts by exogenous genetic material. However, the
      mechanism underlying membrane electropermeabilization is still largely unknown.
      Evidence is presented here that electroporation under conditions compatible with
      cell survival induces lipid hydroperoxide formation in the membranes of animal
      and plant cells. Exposure to electric fields also enhanced up to 5-fold the
      spontaneous emission of light from both cell types, which paralleled the amount
      of conjugated hydroperoxides detected in cell membranes. The emitted photons were
      mainly in the red edge of the spectrum, suggesting the involvement of singlet
      oxygen. The presence of antioxidants during electroporation did not reduce the
      formation of hydroperoxides nor the permeability but quenched the luminescence.

PMID- 7818527
TI  - Highly conserved aspartate 68, tryptophane 73 and glycine 109 in the N-terminal
      extracellular domain of the human VIP receptor are essential for its ability to
      bind VIP.
AB  - The human VIP receptor belongs to a subfamily of G protein-coupled receptors that
      includes secretin, glucagon and several other receptors. We have used site
      directed mutagenesis to investigate the requirement of highly conserved aspartate
      68 (mutant D68G), tryptophane 73 (mutant W73G), proline 87 (mutant P87G), glycine
      109 (mutant delta 109) and tryptophane 110 (mutant W110G) for the ability of the
      human VIP receptor to bind VIP. After transfection of mutated cDNAs in Cos-7
      cells, it appeared that mutants G87P and W110G bound VIP with the same
      dissociation constant as the wild type receptor whereas mutants W73G, P87G and
      delta 109 did not bind VIP. Since all mutated receptor proteins were synthesized
      by Cos-7 cells (Western blot) and expressed at the plasma membrane level
      (immunofluorescence studies), it is concluded that the N-terminal extracellular
      domain of the human VIP receptor contains highly conserved amino acid residues
      which are essential for its intrinsic binding activity.

PMID- 7818529
TI  - Cochaperonins are histone-binding proteins.
AB  - Cochaperonins (cpn10) assist chaperonins (cpn60) in mediating folding of
      polypeptide substrates in an ATP-dependent reaction. Moreover, they have been
      shown to be secretory products of living cells and to perform discrete biological
      activities without the need to interact with cpn60. Here, we have investigated
      the possible existence of cellular cpn10 binding sites that could mediate such
      activities. For this purpose, we performed binding studies with iodinated cpn10
      on whole cells and on electrophoretically separated eukaryotic cell lysates. The
      former studies yielded negative results, whereas in the latter binding to several
      proteins was detected. These proteins were identified as being histones. Binding
      was observed to all core histones (H2A, H2B, H3 and H4) and, although weaker, to
      the linker histone H1 as well. These results show that cpn10 are histone-binding
      proteins.

PMID- 7818528
TI  - The minimal active domain of the mouse ras exchange factor CDC25Mm.
AB  - The minimal active domain of the mouse CDC25Mm, a GDP/GTP exchange factor (GEF)
      active on H-ras protein, was determined by constructing several deletion mutants
      of the C-terminal domain of the protein. The functional activity of these
      fragments was analyzed for the ability to complement the yeast temperature
      sensitive mutation cdc25-1 and to catalyze the GDP/GTP exchange on Ras proteins
      in vitro. A C-terminal domain of 256 residues (CDC25Mm 1005-1260) was sufficient
      for full biological activity in vivo. Deletion of 27 C-terminal amino acids
      (CDC25Mm 1005-1233) abolished the complementing activity while deletion of 25 N
      terminal residues (CDC25Mm 1030-1260 corresponding to the most conserved domain)
      led to a complete loss of expression. The results in vivo were supported by
      experiments in vitro. Highly purified CDC25Mm 1005-1260, expressed in E. coli
      using the pMAL system, enhanced the GDP release from both H-ras p21 and S.
      cerevisiae Ras2p and its activity was nearly as high as that of CDC25Mm 974-1260.
      Comparison with the Cdc25p protein yielded further evidence that the minimal
      active domain of CDC25Mm is shorter than the yeast one.

PMID- 7818530
TI  - Lipoprotein lipase: role of intramolecular disulfide bonds in enzyme catalysis.
AB  - Lipoprotein lipase (LPL) catalyzes the hydrolysis of the triacylglycerol
      component of triacylglycerol-rich lipoproteins. There are 4 cysteine pairs that
      are completely conserved among LPLs of all species known. We examined the
      functional importance of each of the cysteine pairs in enzyme catalysis by
      examining LPLs produced in Cos cells by transfection. Immunoreactive LPL was
      produced by vectors encoding the wildtype LPL and each of the 4 cysteine-pair
      mutant LPLs. Enzyme activity was detectable in the wildtype enzyme, but not in 3
      of the 4 Cys-->Ser mutant enzymes (C216S/C239S, C264S/C275S, and C278S/C283S).
      Interestingly, LPL activity was also present in the mutant (C418S/C438S), which
      affects the C-terminal cysteine pair, with a specific activity approximately 50%
      higher than that of wildtype. There is evidence that LPL contains two distinct
      domains consisting of the N-terminal three-quarters of the sequence connected by
      a flexible region to the C-terminal domain comprising the rest of the molecule.
      The conservation of catalytic function despite the disruption of the only
      disulfide bridge in the C-terminal domain of LPL indicates that the two domains
      can function independently of each other in enzyme catalysis.

PMID- 7818531
TI  - The PI3-kinase serine kinase phosphorylates its p85 subunit and IRS-1 in PI3
      kinase/IRS-1 complexes.
AB  - Insulin receptor tyrosine kinase activity accounts for tyrosine phosphorylation
      of insulin receptor substrate-1 (IRS-1), but the serine kinase(s) responsible for
      serine phosphorylation of IRS-1 is(are) unknown. In vitro kinase assays performed
      on PI3-kinase and IRS-1 immunoprecipitates demonstrated insulin-dependent serine
      phosphorylation of IRS-1. IRS-1 was associated with both insulin-dependent and
      independent serine kinases. Only the insulin-dependent serine kinase preferred
      Mn2+ over Mg2+ and was recovered from cell lysates containing dithiothreitol. In
      complexes of tyrosine phosphorylated recombinant IRS-1 and PI3-kinase,
      phosphorylation of IRS-1 was associated with decreased phosphorylation of the p85
      subunit of PI3-kinase. These results are consistent with PI3-kinase being
      responsible for insulin-dependent serine phosphorylation of IRS-1 and suggest
      that this phosphorylation reaction may affect functions of both IRS-1 and the PI3
      kinase.

PMID- 7818532
TI  - Identification of novel promoter and repressor elements in the 5'-flanking
      regions of the rat insulin-like growth factor-I gene.
AB  - Although the major endocrine source of insulin-like growth factor-I (IGF-I) is
      the liver, little is known about IGF-I transcriptional mechanisms in this tissue.
      To evaluate the role of cis-regulatory elements, rat hepatocytes in primary
      culture were transfected with DNA constructs containing IGF-I 5'flanking
      sequences, fused to a luciferase reporter. We demonstrate the presence of a novel
      promoter approximately 0.5 kb upstream from exon 1 transcription initiation
      sites, together with a repressor element in this region, and a downstream
      repressor element which can modulate the activity of both endogenous and
      heterologous promoters.

PMID- 7818533
TI  - Identification of multiple transcribed sequences from the spinal muscular atrophy
      region of human chromosome 5.
AB  - We report the isolation and characterization of novel expressed sequences from
      the spinal muscular atrophy (SMA) region on human chromosome 5q13. Based on the
      sequence homology studies these cDNAs were grouped in four classes, one of which
      shows extensive homologies with the beta-glucuronidase (BG) gene, differing in
      exon arrangement. The other cDNAs do not show any strong homology with known DNA
      sequences.

PMID- 7818535
TI  - Genomic organization and chromosomal location of the mouse type I BMP-2/4
      receptor.
AB  - We have characterized the structure of a mouse bone morphogenetic protein (BMP)
      type I receptor gene that can bind both BMP-2 and BMP-4. The mouse BMP-2/4
      receptor gene is encoded by 11 exons and spans approximately 38-kb. Most of the
      intron/exon boundaries are not conserved compared to the kinase domain of the
      related, activin type II receptor. In addition, whereas the activin type II
      receptor gene contains large introns (> 40 kb), the largest intron of the BMP-2/4
      receptor gene is only 6.4-kb. The BMP-2/4 receptor gene (Bmpr) was mapped to
      mouse chromosome 14. Bmpr is closely linked to Rbp3 in the region containing
      pugnose, a mutation that alters bone development. Knowledge of the genomic
      structure of Bmpr provides important information to create Bmpr-deficient mice.

PMID- 7818536
TI  - A novel approach to protein-protein interaction: complex formation between the
      p53 tumor suppressor and the HIV Tat proteins.
AB  - By using a novel genetic approach, based on the properties of lambda cl
      repressor, we demonstrate that the HIV-1 Tat protein specifically interacts with
      the human p53 protein via the p53 O2 dimerization domain. By random and site
      specific mutagenesis, we also identify the residues in Tat and O2 peptides which
      are involved in this interaction. Two alternative biological consequences are
      expected to result from Tat-p53 interaction: (i) Tat-O2 interaction inactivates
      p53 regulation function, thus producing cell transformation; (ii) Tat-O2
      interaction favours the formation of p53 dimers, thus leading the cell towards
      apoptosis.

PMID- 7818534
TI  - Point mutation in the second phosphatase domain of CD45 abrogates tyrosine
      phosphatase activity.
AB  - CD45 is a transmembrane protein tyrosine phosphatase that possesses two
      phosphatase domains in its cytoplasmic region. Whether both domains function
      independently as phosphatase enzymes or whether both domains interact to form an
      active enzyme is unclear. A point mutation of a critical cysteine residue in
      domain I is known to abolish CD45 activity, implying that the catalytic activity
      resides in domain I. In this report, mutational analysis of purified, recombinant
      CD45 cytoplasmic domain protein was performed. It was found that a single amino
      acid change in domain II (glutamine 1180 to a glycine) resulted in an inactive
      phosphatase enzyme, whereas two other point mutations in the membrane proximal
      region of the molecule had no effect on activity. Deletion of the region linking
      the two phosphatase domains also abolished enzymatic activity. Amino acids
      crucial for phosphatase activity thus reside in both phosphatase domains of CD45,
      illustrating that the phosphatase domains of CD45 do not act independently, but
      are both required for the phosphatase activity of CD45.

PMID- 7818537
TI  - Involvement of the Sonic hedgehog gene in chick feather formation.
AB  - To elucidate the molecular mechanisms of chick feather formation, we observed
      expression patterns of the Sonic hedgehog (Shh) gene, which is one of the
      vertebrate homologs of the Drosophila segment polarity gene, hedgehog, and
      encodes a signaling molecule functioning in limb pattern formation and motor
      neuron induction. We found that the Shh gene is also expressed in the apical
      region of the feather placodes and then in nine to eleven longitudinal stripes
      along feather filaments. The stripe was found to correspond to one of the outer
      marginal zones of each barb ridge, termed the zone of Shh expression. No
      significant expression signal was detected in the scale bud of developing legs.
      Thus, Shh is likely to function as an epithelial signaling molecule in epithelio
      mesenchymal interaction during feather formation. Furthermore, since genes of
      bone morphogenetic protein-2 (BMP-2) and fibroblast growth factor-4 (FGF-4) are
      coexpressed with Shh during feather formation as observed in limb morphogenesis,
      interactions among FGF-4, Shh and BMP-2 may be involved in formation of feather
      filaments and barbs in a similar fashion as elucidated in limb pattern formation.

PMID- 7818538
TI  - Peroxisomal activation of long- and very long-chain fatty acids in the yeast
      Pichia pastoris.
AB  - In mammals, beta-oxidation of very long-chain fatty acids (VLCFA) takes place in
      peroxisomes. This process is impaired in X-linked adrenoleukodystrophy (XALD)
      patients as a result of decreased activity of peroxisomal very long-chain acyl
      CoA synthetase (VLCS). We investigated VLCFA and long chain fatty acid (LCFA)
      activation in the yeast Pichia pastoris. Both VLCFA and LCFA were activated to
      their CoA derivatives in an organelle fraction. When organelles were fractionated
      on a sucrose gradient, VLCS activity co-localized with peroxisomes while long
      chain acyl-CoA synthetase activity associated primarily with mitochondria.
      Consistent with these findings, only VLCS activity was reduced in organelle
      fractions from peroxisome assembly (pas) mutants. Furthermore, no VLCS activity
      was detected in pas mutants at the density of normal peroxisomes. Thus, we
      conclude that VLCS is a peroxisomal enzyme in P. pastoris and this organism may
      serve as an excellent model system to investigate the molecular basis of XALD.

PMID- 7818539
TI  - A human orphan calcitonin receptor-like structure.
AB  - A novel calcitonin receptor-like protein of 461 amino acids with seven putative
      transmembrane domains has been identified through molecular cloning in a cDNA
      library of the human cerebellum. 91% and 56% of the amino acids are identical in
      a rat orphan calcitonin receptor-like sequence and the human calcitonin receptor,
      respectively. 5.2 kb mRNA is predominantly expressed in the lung, heart and
      kidney. Specific binding of 125I-labeled salmon calcitonin and human calcitonin
      gene-related peptide-I to COS-7 cells transiently transfected with the receptor
      cDNA was less then 0.5%. Cellular cAMP accumulation was indistinguishable in cDNA
      transfected and non-transfected control COS-7 and renal tubular cells from the
      American opossum stimulated with human and salmon calcitonin, human calcitonin
      gene-related peptide-I and -II, human amylin, human adrenomedullin, lizard
      helodermin, salmon stanniocalcin and chicken parathyroid hormone-related protein.
      The receptor-like protein whose ligand remains to be discovered belongs to the
      family of receptors of calcitonin, parathyroid hormone, secretin, vasointestinal
      peptide and pituitary adenylate cyclase-activating polypeptide.

PMID- 7818540
TI  - A soluble cellular factor directly stimulates Ca2+ entry in neutrophils.
AB  - A soluble factor, extracted from neutrophils and P388D1 cells, stimulated a
      transient rise in cytosolic free Ca2+ and a small increase in the permeability to
      Mn2+ in fura2-loaded neutrophils. These effects were not prevented by blockade of
      formylated peptide receptors by t-boc-met-leu-phe. The rise in cytosolic free
      Ca2+ was partly attributed to transmembrane influx and partly due to store
      release. Ca2+ store release but not transmembrane influx was inhibited by the PLC
      inhibitor, U73122, demonstrating a direct effect of the factor on channel
      opening. It was concluded that the soluble cellular factor directly stimulated
      Ca2+ entry in neutrophils.

PMID- 7818541
TI  - The kinetics of the acid-induced conformational change of influenza virus
      haemagglutinin can be followed using 1,1'-bis(4-anilino-5-naphthalenesulphonic
      acid).
AB  - 1,1'-Bis(4-anilino-5-naphthalenesulphonic acid) (bis-ANS) has been shown by
      fluorescence spectroscopy to bind to bromelain-cleaved influenza haemagglutinin
      (BHA). The fluorescence intensity of 1.2 microM bis-ANS in the presence of BHA in
      its low-pH conformation is twenty-fold higher than in the presence of BHA in its
      neutral-pH conformation. The use of this probe provides a sensitive method for
      investigating the kinetics of the irreversible conformational change of BHA
      induced by low pH. At pH5.0 the reaction is described by a rapid burst followed
      by a double exponential increase in the fluorescence of bis-ANS, with rate
      constants of 5.2 +/- 0.9 x 10(-3) sec-1 and 6.7 +/- 1.9 x 10(-4) sec-1. This
      reaction is sensitive to the presence of tert-butylhydroquinone, an inhibitor of
      the conformational transition of BHA. The dependence of the reaction rate on pH
      indicates that the acid-induced conformational change is dependent upon the
      multiple protonation of the neutral-pH conformation of BHA.

PMID- 7818542
TI  - Use of site-directed mutagenesis to identify the galactosyltransferase binding
      sites for UDP-galactose.
AB  - Site-directed mutagenesis was utilized to identify binding sites for UDP
      galactose in galactosyltransferase (EC 2.4.1.22). Mutant cDNAs were generated by
      a procedure based on PCR, and the mutated enzymes were expressed in E.coli cells.
      The mutant enzymes were purified by Ni-NTA Sephadex, and the degree of
      purification was judged by SDS-PAGE. Purified mutant GTs, F305L, P306V, N307S,
      N308S, showed dramatic decreases in activities in comparison with the activity of
      the wild-type GT. Enzyme kinetic analysis revealed that the Km values of F305L,
      P306V, N307S and N308S for UDP-galactose were, respectively, 9-, 11-, 50- and 20
      fold higher than the Km of wild-type GT, but the Km values for manganese were not
      significantly different from that of the wild-type GT. The quartet mutant
      F305L/P306V/N307S/N308S showed no activity. From the results of this study it is
      concluded that amino acids, Phe-305, Pro-306, Asn-307 and Asn-308, in GT are most
      probably involved in GT catalysis or are located close to the UDP-galactose
      binding region but are not involved in the binding of manganese.

PMID- 7818543
TI  - The antifreeze protein genes of the winter flounder, Pleuronectus americanus, are
      differentially regulated in liver and non-liver tissues.
AB  - The synthesis of winter flounder (Pleuronectus americanus) antifreeze protein
      (AFP) mRNAs in the liver is seasonally regulated by the pituitary gland. With the
      recent discovery that AFP mRNAs are also present in several non-liver tissues,
      the aim of the present investigation was to compare the regulatory mechanisms of
      AFP genes in liver and non-liver tissues. Northern blot analyses indicate that
      the level of liver AFP mRNA undergoes a several hundred fold difference between
      the winter and summer months, while AFP mRNAs from gills and kidneys exhibit only
      a modest 5-10 fold seasonal variation. As expected, the liver AFP mRNA in the
      hypophysectomized fish was increased by over 40 fold. However, no significant
      increase was observed for the non-liver AFP mRNAs upon hypophysectomy. These
      investigations suggest that AFP mRNAs in liver and non-liver tissues are
      differentially regulated.

PMID- 7818544
TI  - Synthesis of non-translating or translating specialized ribosomes causes feedback
      regulation of ribosomal RNA synthesis in Escherichia coli.
AB  - Specialized ribosomes carry a mutant anti-Shine-Dalgarno region that disrupts the
      complementary base pairing that stabilizes the translation initiation complex
      with E. coli mRNAs. It has been reported that production of specialized ribosomes
      does not cause the inhibition of chromosomal rRNA synthesis that follows
      production of wild-type ribosomes. We proposed that enabling translation on
      specialized ribosomes by providing mRNA with a complementary mutation in the
      Shine-Dalgarno region would restore feedback regulation and inhibit chromosomal
      rRNA synthesis. With both our system and the system studied previously, we saw
      feedback regulation regardless of whether the specialized ribosomes were
      translating. As reported previously, transcription from plasmid-borne promoters
      decreased as chromosomal rRNA synthesis was repressed, suggesting that the lambda
      PL and tac promoters may be sensitive to the effector(s) of feedback regulation.

PMID- 7818545
TI  - Lithium in the mating response and cell cycle of Saccharomyces cerevisiae.
AB  - Studies with Li+, an inhibitor of phosphoinositide metabolism, demonstrated that
      an early response of Saccharomyces cerevisiae to a-factor pheromone was
      negatively affected by this cation. This was monitored by the production of beta
      galactosidase from a reporter construct containing the promoter region of the
      yeast STE3 gene and the coding region of the E. coli LacZ gene. Growth and
      progression through the cell cycle were also affected by Li+ and analysis of
      budded/unbudded ratios revealed that Li+ caused yeast cells to arrest in G1.
      These data provide support for the role of inositol phosphates in the mating
      response and cell cycle of Saccharomyces cerevisiae.

PMID- 7818546
TI  - Mucosal T cells induce systemic anergy for oral tolerance.
AB  - Heat-labile enterotoxin (LT) from enterotoxigenic Escherichia coli is known to
      possess strong immunoregulatory potential in terms of inhibition of the induction
      of oral tolerance and adjuvanticity in oral immunization. We found that oral
      administration of an immunogenic peptide of LT [LT-B(26-45); spanning the
      residues 26-45 of LT-B] induced systemic unresponsiveness in BALB/c mice
      resulting in diminished serum IgG responses. It was also shown that the spleen
      (SP) CD4+ T cells of tolerized mice failed to proliferate, whereas the Peyer's
      patches (PP) CD4+ T cells responded to the peptide. RT-PCR revealed that the SP
      CD4+ T cells did not generate IL-2 mRNA, while the PP CD4+ T cells expressed
      significant levels of IFN-gamma, IL-2, IL-4, and TGF-beta mRNA. Adoptive transfer
      of LT-B-specific intraepithelial lymphocytes to the tolerant mice abrogated the
      tolerance. In the reversed mice, LT-B(26-45)-stimulated SP CD4+ T cells expressed
      significant levels of IFN-gamma, IL-2, IL-4, and IL-6 mRNA. These results
      indicate that PP CD4+ T cells induce oral tolerance due to systemic T cell
      anergy.

PMID- 7818547
TI  - Sites and mechanisms of low-level oxidative stress in cultured cells.
AB  - Oxidative stress is involved in a multitude of pathological conditions. In the
      present study, we investigated the cellular targets and the mechanisms of low
      level oxidative stress in a Chinese Hamster Ovary cell culture. Oxidative stress
      was induced either by continuous enzymatic production of superoxide or by bolus
      addition of hydrogen peroxide (H2O2). Low-level oxidative stress irreversibly
      impaired the reproductive capacity of the cells in the absence of damage to
      membrane integrity or energy metabolism. Cells were protected by catalase but not
      by superoxide dismutase, indicating that H2O2, not superoxide, was the causative
      agent of cell damage. Nitroxide spin labels decreased hydroxyl radical (.OH)
      formation and protected cells from the oxidative stress. The differing membrane
      permeabilities of these spin labels suggest that the damage is localized on the
      cell surface. Oxidative stress to DNA and RNA was not significant, as shown by
      levels of guanine hydroxylation products. A mechanism is proposed whereby low
      level oxidative stress acts at the cell surface to cause impairment of cell
      reproduction.

PMID- 7818548
TI  - A protein kinase C isozyme, nPKC epsilon, is involved in the activation of NF
      kappa B by 12-O-tetradecanoylphorbol-13-acetate (TPA) in rat 3Y1 fibroblasts.
AB  - In order to examine whether PKC is involved in the activation of NF-kappa B by
      TPA, we overexpressed a variety of PKC isozymes in rat 3Y1 fibroblasts and
      monitored the expression of the co-transfected reporter NF-kappa B gene. In
      contrast to TPA response element (TRE), where overexpression of a variety of PKC
      isozymes results in enhanced activation by TPA, activation of NF-kappa B by TPA
      is not enhanced by overexpression of PKC isozymes such as cPKC alpha, nPKC delta,
      or nPKC theta. However, the overexpression of nPKC epsilon does result in
      enhancement. A kinase-negative point mutant of nPKC epsilon, where Lys at the ATP
      binding site is altered to Arg, does not cause this enhancement of NF-kappa B
      activation. Further, the kinase-negative nPKC epsilon partially suppresses
      endogenous NF-kappa B activity. These results suggest that nPKC epsilon is
      specifically involved in the activation of NF-kappa B when cells are treated with
      TPA.

PMID- 7818549
TI  - A small peptide derived from the aminoterminus of c-Raf-1 inhibits c-Raf-1/Ras
      binding.
AB  - Various domains of the aminoterminal part of c-Raf-1 expressed as glutathione-S
      transferase fusion proteins were analyzed for Ras binding. The binding site was
      localized at the aminoterminus outside of the cysteine-rich region. A single
      aminoacid exchange at aminoacid residue 89 (Arg89 to Leu) of c-Raf-1 inhibits
      binding. A small synthetic peptide corresponding to c-Raf-1 aminoacids 77 to 101
      comprising Arg89 in a central position competes for Ras binding and thereby
      characterizes the relevant binding domain of Ras on c-Raf-1.

PMID- 7818550
TI  - Glucocorticoid effects on glucose transport and transporter gene expression in L6
      muscle cells.
AB  - We questioned whether glucocorticoids alter the known potent effect of serum to
      increase glucose transport and GLUT-1 expression in cultured L6 myotubes.
      Myotubes were exposed to serum-free medium for 24h in the presence or absence of
      300 nM dexamethasone and subsequently treated for 8h with 10% serum or serum free
      medium in the continued presence or absence of the glucocorticoid. Dexamethasone
      did not effect the serum-induced increase in GLUT-1 mRNA. However, dexamethasone
      increased GLUT-1 mRNA 2-3 fold versus the absence of dexamethasone after serum
      withdrawal. Dexamethasone also resulted in higher GLUT-1 protein levels and
      ameliorated the loss of glucose transport activity seen after serum withdrawal.

PMID- 7818551
TI  - Phosphorylation of dystrophin:effects on actin binding.
AB  - Dystrophin is phosphorylated by several protein kinases. In this work, we have
      studied the effects of dystrophin phosphorylation on the binding to actin.
      Purified dystrophin was phosphorylated in vitro by the catalytic subunit of cAMP
      dependent protein kinase (PKA), casein kinase II (CK-II), and protein kinase c
      (PKC). The results demonstrate that phosphorylation of dystrophin by PKA
      phosphorylation caused a three fold increase in dystrophin binding to actin. In
      contrast, phosphorylation by CK-II or PKC inhibited the binding to actin. These
      results indicate that phosphorylation of dystrophin modulates its interaction
      with the actin cytoskeleton. It is suggested that phosphorylation may be one
      mechanism for regulating protein turnover in muscle membrane-skeleton.

PMID- 7818552
TI  - Induction of membrane proliferation by poliovirus proteins 2C and 2BC.
AB  - Poliovirus infection leads to the appearance of a number of cytoplasmic vacuoles
      involved in the replication of virus genomes. To characterize the viral proteins
      involved in membrane proliferation different poliovirus proteins have been
      expressed in HeLa cells. Two recombinant vaccinia viruses have been obtained that
      express poliovirus protein 2C, one under the 5' untranslated (UTR) sequence of
      poliovirus and another under the leader region of EMC virus. Expression of 2C was
      very efficient in both cases, although better results were obtained when
      poliovirus 2C was expressed under the 5'UTR sequence of EMC virus. Transient
      expression of poliovirus proteins 2B, 2C or 2BC placed under a T7 promoter was
      analyzed using a recombinant vaccinia virus that contains the bacteriophage T7
      RNA polymerase. The expression of 2C, or 2BC, contrary to 2B, was able to induce
      the proliferation of vacuoles morphologically similar to those found during
      poliovirus infection. These findings indicate that poliovirus protein 2C, in
      addition to its NTPase and RNA binding activities, is also endowed with the
      capacity to induce the formation of cytoplasmic vacuoles.

PMID- 7818553
TI  - Effect of anchor residue modifications on the stability of HLA-A11/peptide
      complexes.
AB  - MHC class I antigens bind peptides derived from endogenous proteins and present
      them to cytotoxic T lymphocytes. This binding is selective and shows high allele
      specificity. Peptides binding to HLA-A11 contain a hydrophobic or a small polar
      amino acid at position 2 and a lysine at the carboxy terminus. Peptide analogues,
      derived from previously identified high affinity peptides and carrying amino acid
      substitutions in position 2, were used to determine the requirements for
      formation of stable HLA-A11/peptide complexes. By kinetic analysis we were able
      to discriminate among apparent and true binders. Only analogues carrying in
      position 2 the amino acids valine, threonine and isoleucine formed stable
      complexes with HLA-A11 with a half life > or = 72 hours.

PMID- 7818555
TI  - Molecular cloning of human cDNA for cathepsin K: novel cysteine proteinase
      predominantly expressed in bone.
AB  - We have previously cloned a rabbit cDNA clone (OC-2) from an osteoclast cDNA
      library by the differential screening. OC-2 was found to encode a novel cysteine
      proteinase, tentatively called cathepsin K, which is predominantly expressed in
      osteoclasts. By use of a rabbit OC-2 fragment as a probe, its human counterpart
      was cloned from a cDNA library of osteoarthritic hip bone. The cloned human cDNA
      (hOC-2) encoded a protein of 329 amino acid residues and its deduced amino acid
      sequence showed 94% homology to rabbit cathepsin K. Multiple alignment of amino
      acid sequences of human cathepsins B, H, L, S and K showed the highest homology
      of cathepsin K to cathepsin S 48%. Northern blot analysis showed that cathepsin K
      mRNA is expressed at high levels in some osteoarthritic hip bones and at a very
      high level in osteoclastoma compared to very low levels in other tissues. These
      results suggest that cathepsin K is closely involved in human osteoclastic bone
      resorption.

PMID- 7818554
TI  - Regulation of cyclins and p34CDC2 expression during terminal differentiation of
      C2C12 myocytes.
AB  - Little is known about the expression of cell cycle regulatory genes upon terminal
      differentiation of skeletal muscle cells. In this report, we demonstrate that the
      expressions of cyclin A, cyclin D1 and p34cdc2 are downregulated upon C2C12
      myocytes differentiation and are not inducible in differentiated myotubes. SV40
      large T antigen can induce cell cycle entry of myotubes through its induction of
      these genes' expressions and pRB phosphorylation as well as its suppression of Rb
      expression. These results provide the first direct evidence that the irreversible
      downregulation of cyclins and cyclin-dependent kinases is one mechanism for the
      permanent cell cycle withdrawal of myotubes.

PMID- 7818556
TI  - Binding of the LXCXE insulin motif to a hexapeptide derived from retinoblastoma
      protein.
AB  - Peptides corresponding to retinoblastoma protein (RB) fragment 649-654 (LFYKKV)
      were tested for their ability to recognize the LXCXE sequence motif in human
      papilloma virus type 16E7 protein (HPV-16E7) encompassing E7 residues 21-26
      (DLYCYE) and an identical motif in human insulin comprising insulin B-chain
      residues 16-21 (YLVCGE), respectively. Interaction between these complementary
      peptide sequences was observed by several approaches, including direct and
      competitive ELISA as well as affinity chromatography. Moreover, we demonstrated
      that immobilized RB649-654 displays specific recognition properties towards full
      length insulin. Hence, this study provides a first experimental support for the
      previously anticipated complex formation between insulin and RB.

PMID- 7818557
TI  - Raynaud's phenomenon and scleroderma. Dysregulated neuroendothelial control of
      vascular tone.

PMID- 7818558
TI  - Abnormal vitamin B6 status in rheumatoid cachexia. Association with spontaneous
      tumor necrosis factor alpha production and markers of inflammation.
AB  - OBJECTIVE: To compare vitamin B6 levels in rheumatoid arthritis (RA) patients and
      healthy control subjects. METHODS: We measured levels of vitamin B6 in 23 adults
      with well-controlled RA, and in 23 healthy control subjects matched for age, sex,
      race, and weight. RESULTS: Although plasma folate and vitamin B12 concentrations
      and erythrocyte B6 activity coefficients were similar in the patients and
      controls, plasma levels of pyridoxal-5'-phosphate (PLP) were lower in the RA
      patient group (mean +/- SD 46.1 +/- 48.1 versus 69.3 +/- 58.4 nmoles/liter; P <
      0.004). In multivariate analyses, PLP was inversely associated with tumor
      necrosis factor alpha (TNF alpha) production by peripheral blood mononuclear
      cells (PBMC) (P < 0.001), after adjustment for age, pain score, erythrocyte
      sedimentation rate, and use of nonsteroidal antiinflammatory drugs. CONCLUSION:
      PLP levels are reduced in patients with RA. This reduction is associated with TNF
      alpha production by PBMC.

PMID- 7818559
TI  - Mannose-binding protein gene polymorphism in systemic lupus erythematosus.
AB  - OBJECTIVE: To determine whether an allelic form of mannose-binding protein (MBP)
      incapable of activating complement is associated with susceptibility to systemic
      lupus erythematosus (SLE). METHODS: MBP allele frequencies were determined by
      amplification refractory mutation system-polymerase chain reaction in 102 white
      SLE patients and 136 controls. RESULTS: The MBP allele that is unable to activate
      complement was present in 42 SLE patients (41%) and in 41 controls (30%) (P =
      0.08, odds ratio [OR] = 1.6, 95% confidence interval [95% CI] 1.0-2.8). The gene
      frequency of this allele was 0.25 in SLE patients and 0.19 in controls (P = 0.08,
      OR = 1.5, 95% CI 1.0-2.3). CONCLUSION: Our results suggest that this allele of
      the MBP gene represents a minor risk factor for SLE.

PMID- 7818560
TI  - Transfer of experimental antiphospholipid syndrome by bone marrow cell
      transplantation. The importance of the T cell.
AB  - OBJECTIVE: To investigate the potential of bone marrow cells from mice with
      primary antiphospholipid syndrome (APS) to transfer the disease to naive mice,
      and to determine the importance of the role of T cells in the APS. METHODS:
      Experimental primary APS was induced in naive mice following active immunization
      with anticardiolipin (aCL) monoclonal antibody (MAb). Whole-population or T cell
      depleted bone marrow cells from mice with experimental primary APS were infused
      into total body-irradiated naive BALB/c recipients. RESULTS: Bone marrow cells
      (in the presence of T cells) had the potential to induce experimental APS in
      naive mice, which resulted in high serum titers of aCL, antiphosphatidylserine,
      and antiphosphatidylinositol antibodies; an increased number of antibody-forming
      cells specific for each of the above phospholipids; a positive lymph node cell
      proliferative response to aCL MAb; and clinical features of primary APS,
      including thrombocytopenia, prolonged activated partial thromboplastin time
      (indicating the presence of lupus anticoagulant), and a high frequency of fetal
      resorptions (the equivalent of human fetal loss). T cell-depleted bone marrow
      cells did not transfer the disease. CONCLUSION: This study demonstrates the
      important role of T cells in the development and transfer of experimental primary
      APS and raises the possibility of T cell manipulations in treatments to prevent
      this condition.

PMID- 7818561
TI  - Analysis of the Mi-2 autoantigen of dermatomyositis.
AB  - OBJECTIVE: To determine the biochemical structure and antigenic components of Mi
      2 autoantigen, the target of autoantibodies in 15-20% of dermatomyositis
      patients. METHODS: Immunoprecipitation from 35S-labeled HeLa cell extract,
      immunoblotting, and purification from bovine thymus by immunoaffinity
      chromatography. RESULTS: All 46 sera that had anti-Mi-2 autoantibodies
      demonstrated by immunodiffusion immunoprecipitated a major protein of
      approximately 240 kd. Additional proteins of 200, 150, 72, 65, 63, 50, and 34 kd
      appeared to be part of the antigen. Fractions of purified bovine Mi-2 with
      antigenic activity showed high molecular weight bands comparable with
      immunoprecipitated HeLa Mi-2. Twenty-four of 47 anti-Mi-2 positive sera reacted
      with the 240-kd protein by immunoblot against anti-Mi-2 immunoprecipitates.
      CONCLUSION: Mi-2 antigen consists of multiple proteins, of which the 240-kd
      protein appears to be the major reactive component.

PMID- 7818562
TI  - Measurement of radiographic changes in adjuvant-induced arthritis in rats by
      quantitative image analysis.
AB  - OBJECTIVE: To apply quantitative analytical methods to the evaluation of
      radiographic images in experimental arthritis. METHODS: Adjuvant was used to
      induce arthritis in rats. Arthritis progression was followed by conventional
      methods. In addition, digitized images of radiographs of the calcaneus were
      examined for changes in the mean and in the distribution pattern of gray values.
      Periosteal new bone formation was measured as an increase in image area of the
      calcaneus. RESULTS: Significant changes in the gray value profile and increases
      in periosteal bone formation occurred in arthritic rats. More extensive changes
      occurred in Lewis rats than in Sprague-Dawley rats. Analysis of serial
      radiographs revealed an initial decrease in the density of juxtaarticular bone,
      followed by progressive increases in gray value variation due to concurrent bone
      loss and bone formation. Eventually, bone formation in arthritic rats resulted in
      increased gray values above those in nonarthritic rats. CONCLUSION: Image
      analysis represents a sensitive, quantitative method for detecting radiographic
      changes in experimental arthritis.

PMID- 7818563
TI  - Spinal involvement in gout.
AB  - A 45-year-old man with severe gout was admitted to the hospital because of
      Staphylococcus aureus septicemia. He had also a biclonal dysglobulinemia, without
      signs of myeloma. An asymptomatic lytic lesion of the left pedicle of L5 was
      discovered on radiographs. Histologic examination of the biopsied lesion showed
      typical tophaceous gout.

PMID- 7818564
TI  - Azathioprine-related bone marrow toxicity and low activities of purine enzymes in
      patients with rheumatoid arthritis.
AB  - OBJECTIVE: Azathioprine (AZA) metabolism largely parallels the endogenous purine
      pathways. To date, thiopurine methyltransferase (TPMT) deficiency has been
      reported as a cause of AZA-related bone marrow toxicity in 1 patient with
      rheumatoid arthritis (RA). We therefore studied purine enzyme activities in 3
      patients with RA who experienced AZA-related bone marrow toxicity. METHODS:
      Lymphocyte activity of purine nucleoside phosphorylase and 5'-nucleotidase (5NT)
      and erythrocyte activity of TPMT, key enzymes in thiopurine catabolism, were
      measured in 3 RA patients who had experienced AZA-related bone marrow toxicity
      and in 16 RA patients without signs of toxicity despite at least 6 months of
      treatment with AZA. RESULTS: Two patients with AZA-related bone marrow toxicity
      were found to have a TPMT deficiency, 1 partial and 1 total. In the third
      patient, 5NT activity was found to be well below the lowest level observed in the
      control subjects. CONCLUSION: All 3 patients with severe AZA-related bone marrow
      toxicity had abnormal purine enzyme activities. Deficiency of purine enzymes,
      including TPMT and 5NT, may be a cause of AZA-related bone marrow toxicity in
      patients with RA.

PMID- 7818565
TI  - Inhibition of complement activation by intravenous immunoglobulins.

PMID- 7818566
TI  - Nomenclature and classification of vasculitis.

PMID- 7818567
TI  - The prevalence and characteristics of fibromyalgia in the general population.
AB  - OBJECTIVE: To determine the prevalence and characteristics of fibromyalgia in the
      general population. METHODS: A random sample of 3,006 persons in Wichita, KS,
      were characterized according to the presence of no pain, non-widespread pain, and
      widespread pain. A subsample of 391 persons, including 193 with widespread pain,
      were examined and interviewed in detail. RESULTS: The prevalence of fibromyalgia
      was 2.0% (95% confidence interval [95% CI] 1.4, 2.7) for both sexes, 3.4% (95% CI
      2.3, 4.6) for women, and 0.5% (95% CI 0.0, 1.0) for men. The prevalence of the
      syndrome increased with age, with highest values attained between 60 and 79 years
      (> 7.0% in women). Demographic, psychological, dolorimetry, and symptom factors
      were associated with fibromyalgia. CONCLUSION: Fibromyalgia is common in the
      population, and occurs often in older persons. Characteristic features of
      fibromyalgia--pain threshold and symptoms--are similar in community and clinic
      populations, but overall severity, pain, and functional disability are more
      severe in the clinic population.

PMID- 7818568
TI  - Rheumatoid arthritis treated with tenidap and piroxicam. Clinical associations
      with cytokine modulation by tenidap.
AB  - OBJECTIVE: To compare the effects of tenidap and piroxicam on acute-phase protein
      and cytokine levels in the blood of rheumatoid arthritis (RA) patients and to
      explore their associations with clinical disease activity. METHODS: A double
      blind, randomized, crossover trial in 49 patients with active RA compared 6 weeks
      of treatment with tenidap (120 mg/day) versus 6 weeks of treatment with piroxicam
      (20 mg/day). RESULTS: Median values for C-reactive protein (CRP), Westergren
      erythrocyte sedimentation rate (ESR), serum amyloid A (SAA) protein, and
      interleukin-6 (IL-6) were significantly lower after tenidap treatment compared
      with piroxicam treatment, even in the presence of stable background treatment
      with prednisone, methotrexate, or prednisone plus methotrexate. The median within
      patient treatment differences (after tenidap minus after piroxicam) in the CRP,
      ESR, SAA, and IL-6 values were -1.7 mg/dl, -10.0 mm/hour, -22.0 micrograms/ml,
      and -3.7 pg/ml, respectively, and represent -60.4%, -17.7%, -35.5%, and -26.1% of
      the respective baseline levels. IL-6 levels were positively correlated with CRP
      and SAA. Plasma IL-1 beta was generally below the level of detection. Tumor
      necrosis factor alpha levels were similar after tenidap and after piroxicam.
      Treatment differences for 4 of 7 clinical parameters favored tenidap, but did not
      reach statistical significance. IL-6, CRP, and ESR were significantly correlated
      with clinical treatment differences. Tenidap and piroxicam toleration were
      similar, although tenidap-treated patients exhibited a reversible increase in
      urinary protein excretion. CONCLUSION: Tenidap was differentiated from piroxicam
      by lower levels of acute-phase proteins, ESR, and IL-6 after tenidap treatment.
      These treatment differences were significantly correlated with clinical
      parameters.

PMID- 7818569
TI  - Validity and reliability of the twenty-eight-joint count for the assessment of
      rheumatoid arthritis activity.
AB  - OBJECTIVE: To investigate the validity of the 28-joint count for assessment of
      joint involvement in patients with rheumatoid arthritis (RA). METHODS: Joint
      involvement as determined by the 28- and the 66/68-joint count was compared using
      data from 735 prospectively studied RA patients. RESULTS: The joints included in
      the 28-joint count were more commonly involved than other joints, and findings
      from the 28-joint count correlated highly with those from the 66/68-joint count
      in all analyses. CONCLUSION: The 28-joint count is a reliable and valid measure
      for joint assessment. It is easier to perform than the 66/68-joint count, and it
      addresses the joints that are critically involved.

PMID- 7818570
TI  - Modified disease activity scores that include twenty-eight-joint counts.
      Development and validation in a prospective longitudinal study of patients with
      rheumatoid arthritis.
AB  - OBJECTIVE: The development and validation of Modified Disease Activity Scores
      (DAS) that include different 28-joint counts. METHODS: These scores were
      developed by canonical discriminant analyses and validated for criterion,
      correlational, and construct validity. The influence of disease duration on the
      composition of the DAS was also investigated. RESULTS: No influence of disease
      duration was found. The Modified DAS that included 28-joint counts were able to
      discriminate between high and low disease activity (as indicated by clinical
      decisions of rheumatologists). CONCLUSION: The Modified DAS are as valid as
      disease activity scores that include more comprehensive joint counts.

PMID- 7818571
TI  - The development of depressive symptoms among women with rheumatoid arthritis. The
      role of function.
AB  - OBJECTIVE: To examine the role of function and functional changes in the
      development of depressive symptoms among women with rheumatoid arthritis (RA).
      METHODS: Data from a longitudinal panel study of persons with RA were used.
      Functional changes were assessed from 1989 to 1991, and depressive symptoms
      during 1992. RESULTS: Loss of valued activities was a significant risk factor for
      the developing depressive symptoms (i.e., score of > or = 7 on the Short Form
      Geriatric Depression Scale), but overall functional decline was not. CONCLUSION:
      The aspect of functional decline that leads to development of depressive symptoms
      is the loss of valued activities, not simply the functional impairment.

PMID- 7818572
TI  - Nonsteroidal antiinflammatory drugs and the gastrointestinal tract. The double
      edged sword.

PMID- 7818573
TI  - The clenched fist syndrome. A psychiatric syndrome mimicking reflex sympathetic
      dystrophy.
AB  - We describe a patient with swelling and pain in his right hand, which persisted
      for 1 year after minimal trauma. We think this represents a case of "clenched
      fist syndrome," a conversion disorder with unique somatic features that is easily
      mistaken for reflex sympathetic dystrophy syndrome. Included is a comparison of
      other psychological illnesses in which unusual physical findings involve the
      hand.

PMID- 7818574
TI  - Environmental and genetic factors affecting bone mass. Similarity of bone density
      among members of healthy families.
AB  - OBJECTIVE: To evaluate the relative importance of environmental and genetic
      factors in the determination of bone mineral density (BMD) and to quantify the
      risk of low BMD in healthy young adults in relation to the BMD of their parents.
      METHODS: Dual-energy x-ray absorptiometry study of a series of 129 nuclear
      families (441 subjects), including 183 children over age 15, was performed.
      Correlation of BMD in children with BMD in their parents was studied in a linear
      model, taking into account environmental factors. Logistic regression was used to
      quantify the relative risk of lower BMD according to the parents' BMD level.
      RESULTS: BMD was significantly correlated with weight, height, and body mass
      index (BMI) in all family members, and with parents' alcohol consumption and with
      physical activity in fathers and sons. The BMD of the children correlated with
      that of their parents (r = 0.27). The child's BMI, his/her father's BMD and daily
      calcium intake, and his/her mother's BMD, BMI, and body fat accounted for 41.4%
      of the variance in the child's BMD. A son had a 3.8 times higher risk of having a
      low BMD if his father had a low BMD, and a daughter had a 5.1 times higher risk
      if her mother had a low BMD. CONCLUSION: The BMD of children in healthy families
      was related to the BMD of their parents as well as to environmental factors,
      confirming the contribution of genetic inheritance in the determination of bone
      density in young adults, especially in girls.

PMID- 7818576
TI  - Correlation between synovial fluid markers of cartilage and bone turnover and
      scintigraphic scan abnormalities in osteoarthritis of the knee.
AB  - OBJECTIVE: To test the hypothesis that scintigraphic evidence of bone activity
      will correlate with biochemical evidence of increased matrix turnover in
      osteoarthritis (OA). METHODS: Keratan sulfate epitope (5D4), chondroitin sulfate
      epitope (3B3), and osteocalcin (OC) were measured in synovial fluid (SF) from 35
      patients with knee OA, within 1 month of bone scan. RESULTS: SF OC levels
      correlated with 5D4 levels (r = 0.32, P = 0.047) and with abnormalities on
      scintigraphic scan. Mean OC levels were 47% higher (P = 0.016) in patients with
      severely abnormal findings on scans compared with levels in patients with mildly
      abnormal scan findings. No significant association of 5D4 or 3B3 levels and
      perfusion- or late (bone)-phase scintigraphic abnormalities was found.
      CONCLUSION: These data support the hypothesis that there is an association
      between late-phase bone scan abnormalities and SF biochemical markers of bone
      turnover in OA.

PMID- 7818575
TI  - Use of magnetic resonance imaging and P-31 magnetic resonance spectroscopy to
      detect and quantify muscle dysfunction in the amyopathic and myopathic variants
      of dermatomyositis.
AB  - OBJECTIVE: To investigate the use of magnetic resonance imaging (MRI) and P-31
      magnetic resonance spectroscopy (MRS) in characterizing the metabolic and
      functional status of muscles in patients with amyopathic dermatomyositis (DM) and
      to compare the findings with those in patients with classic myopathic DM.
      METHODS: Nine patients with amyopathic DM, 11 patients with myopathic DM, and 11
      normal individuals were studied. MRI images of thigh muscles were obtained, and
      T1 and T2 relaxation times were calculated. Biochemical status was quantitated
      with P-31 MRS, by determining concentrations of phosphate metabolites during rest
      and exercise. RESULTS: Patients with amyopathic DM showed no muscle inflammation,
      and MRS data obtained during rest were normal. During exercise at 25% and 50%
      maximum voluntary contractile force, the MRS data revealed significant
      differences between amyopathic DM patients and control subjects indicating
      inefficient metabolism. In contrast, muscles of patients with myopathic DM showed
      inflammation and metabolic abnormalities even during rest. CONCLUSION: Metabolic
      deficiencies in patients with amyopathic DM were unmasked by exercise, suggesting
      that the 2 DM syndromes may share muscle abnormalities. MRI/MRS may be useful in
      diagnosis and optimization of treatment.

PMID- 7818577
TI  - Increased release of bone sialoprotein into synovial fluid reflects tissue
      destruction in rheumatoid arthritis.
AB  - OBJECTIVE: Bone sialoprotein (BSP) was quantified in synovial fluids and sera
      from rheumatoid arthritis (RA) patients to elucidate whether its release from
      bone relates to the degree of joint tissue destruction. Osteocalcin was assayed
      for comparison. METHODS: BSP and osteocalcin levels were determined by
      immunoassays of knee synovial fluids and of sera from RA patients who were
      selected on the basis of radiographic knee joint tissue damage. RESULTS: Synovial
      fluid concentrations of BSP increased with increasing degrees of knee joint
      damage (rs = 0.6848, P < 0.001). Synovial fluid concentrations of osteocalcin did
      not relate to the degree of joint damage. Serum concentrations of BSP were
      increased, but did not relate to the degree of joint damage. Serum concentrations
      of osteocalcin were normal, but increased within the range of normal during
      progression of joint destruction (rs = 0.4567, P < 0.001). CONCLUSION:
      Quantification of BSP in synovial fluid holds promise as a useful means of
      assessing the degree of tissue damage at the molecular level in patients with RA.

PMID- 7818579
TI  - Elevated interleukin-10 levels in patients with rheumatoid arthritis.
AB  - OBJECTIVE: Interleukin-10 (IL-10) has been shown to exert both antiinflammatory
      and immunostimulatory effects in vivo and in vitro. We therefore sought to
      examine the role of this cytokine in rheumatoid arthritis (RA) by assessing serum
      and synovial fluid IL-10 levels. METHODS: Serum and synovial fluid samples were
      collected from patients with RA and patients with various inflammatory,
      infectious, and noninflammatory arthritides (controls). IL-10 was assayed using
      an IL-10-specific enzyme-linked immunosorbent assay, and messenger RNA (mRNA)
      levels were assessed by semi-quantitative polymerase chain reaction (PCR)
      techniques. RESULTS: Both RA serum and synovial fluid contained significantly
      elevated IL-10 levels compared with levels in normal subjects or in control
      patients (P < 0.01). Some patients with spondylarthropathy also manifested
      increased serum levels of IL-10. Serum levels of IL-10 did not correlate with
      standard measures of clinical activity, but were shown to correlate significantly
      with serum rheumatoid factor (RF) titers and in vitro levels of spontaneous IgM
      RF production (P < 0.05). PCR analyses demonstrated the constitutive expression
      of IL-10 mRNA by the non-T cell population, and semiquantitative PCR analysis
      documented elevated levels of IL-10 mRNA in circulating mononuclear cells of
      those RA patients who were not treated with slow-acting antirheumatic drugs.
      Analysis of IL-10 mRNA revealed the cytokine to be of human, and not viral,
      origin. CONCLUSION: These data suggest that there is increased production of IL
      10 by non-T cells in patients with RA. This may contribute to the diminished T
      cell function and increased antibody and RF production in these patients.

PMID- 7818578
TI  - The role of T cell receptor beta chain genes in susceptibility to rheumatoid
      arthritis.
AB  - OBJECTIVE: To evaluate the role of the T cell receptor beta chain locus (TCRB) in
      genetic susceptibility to rheumatoid arthritis (RA). METHODS: Twenty-eight
      multiplex RA families were recruited from 3 rheumatology outpatient departments.
      All members were genotyped for a highly informative microsatellite (V beta 6.7),
      a V beta 12.2 SSCP marker, and a biallelic C beta restriction fragment length
      polymorphism. Data were analyzed by the SIBPAL program to assess identity-by
      descent in affected sib-pairs. RESULTS: Using the V beta 12.2 marker, there was
      suggestive evidence of increased sib-pair sharing (P = 0.005) in affected
      offspring (a P value of 0.001 is generally taken to establish linkage). Data for
      V beta 6.7 and C beta yielded significance levels of 0.06 and 0.19, respectively.
      CONCLUSION: These data suggest that a gene in or linked to the TCRB complex may
      confer genetic susceptibility to RA in these families. Confirmation in a larger
      panel of families is required.

PMID- 7818580
TI  - Discriminative stimulus properties of diazepam and the novel anxiolytic agent 1
      amino-5-bromouracil in rats.
AB  - A stimulus cue of 1-amino-5-bromouracil (ABU, CAS 127984-93-4) was compared with
      that of diazepam (DZP) using a drug discrimination paradigm in rats. Groups of
      rats were trained to discriminate DZP (1 mg/kg i.p.) or ABU (20 mg/kg i.p.) from
      vehicle. Generalization of the cue of the trained drug to pentobarbital was shown
      in DZP- and ABU-trained rats at a dose of 5 mg/kg. The stimulus cue of ABU showed
      a tendency to generalize to DZP in ABU-trained rats but generalization of that of
      DZP to ABU in DZP-trained rats was only partial. Also partial generalization of
      that of DZP to imipramine and clonidine was found but not to 8-hydroxy-2-(di-n
      propylamino)tetraline (8-OH-DPAT) in DZP-trained rats. Full generalization of the
      stimulus cue of ABU to imipramine and partial generalization of that of ABU to
      clonidine and 8-OH-DPAT was observed in ABU-trained rats. The results suggest
      that the discriminative stimulus properties of ABU differ from those of DZP.

PMID- 7818581
TI  - [The effect of nimodipine on cochlear blood flow in the guinea pig].
AB  - The influence of nimodipine (Nimotop, CAS 66085-59-4), a selectively
      cerebrovascularly acting 1,4-dihydropyridine calcium antagonist, on the cochlear
      blood flow (CBF) was studied in 19 guinea pigs (6 controls). The hydrogen
      clearance measurements were carried out under alpha-chloralose-ethylurethane
      anaesthesia, artificial respiration with simultaneous control of
      electrocardiogram, blood pressure, body temperature and arterial pH (hourly). The
      indirect measurement of CBF was carried out by means of hydrogen clearance in the
      perilymphatic space (basal turn) before and after intravenous application of 1
      microgram nimodipine/kg/min. The mean arterial blood pressure remained within the
      +/- 5% range of the initial value during the experiment. Under treatment with
      nimodipine the CBF showed a non-significant average increase of 4.69% and under
      placebo (20% ethanol, 17% polyethylenglycol 400, citrate buffer), a non
      significant average decrease of 6.16%. The influence of nimodipine on CBF was
      underlined by the overcompensation of the placebo effect.

PMID- 7818582
TI  - Antihypertensive effect of the novel water-soluble calcium antagonist (+/-)-3-(4
      allyl-1-piperazinyl)-2,2-dimethylpropyl methyl 1,4-dihydro-2,6-dimethyl-4-(3
      nitrophenyl)-3,5-pyridinedicarboxylate dihydrochloride in rats.
AB  - The antihypertensive effect of (+/-)-3-(4-allyl-1-piperazinyl)-2,2-dimethylpropyl
      methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate
      dihydrochloride (NKY-722, CAS 117241-46-0) was examined in conscious
      spontaneously hypertensive rats (SHR), normotensive Wistar rats (NWR) and
      anesthetized NWR, and its vasodilatory effect was investigated in the perfused
      NWR mesenteric vascular bed. NKY-722 and nicardipine administered intravenously
      (10-100 micrograms/kg) and orally (0.3-10 mg/kg) lowered blood pressure dose
      dependently with an increase in heart rate in conscious SHR and NWR. The effects
      of NKY-722 were slower in onset and longer-lasting than those of nicardipine, and
      were more marked in SHR than in NWR. The effect of NKY-722 was roughly the same
      as that of nicardipine on intravenous administration. However, NKY-722 was 4-8
      times more potent than nicardipine on oral administration. In anesthetized NWR,
      the hypotensive effects of NKY-722 administered via the femoral vein, portal vein
      and duodenum were examined in comparison with those of nicardipine. The findings
      suggest that NKY-722 is more efficiently absorbed from the gastro-intestinal
      tract and more resistant to the hepatic first pass effect than nicardipine. In
      the perfused NWR vascular bed, NKY-722 and nicardipine (0.01-1.0 microgram)
      attenuated the pressor response to KCl dose-dependently. The effect of NKY-722
      was slower in onset and longer-lasting than that of nicardipine. In conclusion;
      NKY-722 has a potent, slow-onset and long-lasting antihypertensive activity,
      which is mainly attributed to its slow-onset and long-lasting vasodilatory
      action. NKY-722 is expected to be a useful antihypertensive drug.

PMID- 7818583
TI  - Influence of doxazosin on the activity of the endothelium-derived relaxing
      factor.
AB  - This work examined the effect of the selective a1-inhibitor, doxazosin (CAS 74191
      85-8), on the activity of endothelium-derived relaxing factor (EDRF). In vitro,
      the intact thoracic aortic rings of rabbits were contracted with the a-agonist,
      phenylephrine, and then relaxed by sequentially increasing concentrations of the
      EDRF-releasing agent adenosine triphosphate (ATP). In parallel experiments,
      doxazosin (10(-8) mol/l) was added after the contraction but before the addition
      of ATP. Doxazosin enhanced the ATP-induced vasodilation by a factor of 3. Control
      experiments suggested that this was due to the enhanced activity of EDRF, which
      was related to displacement of phenylephrine from a1-adrenoceptors by doxazosin.
      Physiologically relevant concentrations of 6- or 7-hydroxydoxazosin (5 x 10(-10)
      mol/l) had no effect on EDRF activity in vitro. In vivo experiments in the rabbit
      were carried out using bolus, intravenous injections of acetylcholine (ACh),
      which stimulated EDRF release. Threshold doses of doxazosin (2 x 10(-6) g/kg)
      enhanced the hypotensive activity of ACh. Prefeeding the rabbits for 4 weeks with
      a 2% cholesterol diet significantly reduced the sensitivity of the aorta to
      isosorbide-5-mononitrate, a stable EDRF-analog. However, the impairment in
      endothelium-dependent relaxation was attenuated in the presence of doxazosin (2 x
      10(-9) mol/l). The results that in addition to its known antiplatelet activity,
      doxazosin enhances EDRF activity.

PMID- 7818584
TI  - Synthesis and antiplatelet effects of the new antithrombotic agent aspalatone
      with low ulcerogenicity.
AB  - A new compound, aspalatone (acetylsalicylic acid maltol ester), was synthesized
      by esterification of acetylsalicylic acid (ASA) and maltol, an antioxidant, and
      studied for its bleeding time prolongation effect in rats, for its antiplatelet
      aggregation activity in vitro and ex vivo in rats, and for its antithrombotic
      activity in vivo using the mouse thromboembolism test. Aspalatone treatment (15
      mg/kg p.o.) for 10 days prolonged bleeding time by 57% (p < 0.005) in Sprague
      Dawley rats vs control, while ASA treatment (15 mg/kg p.o.) prolonged by 44%. At
      the low dose of 15 mg/kg p.o. at least 8 days of treatment were necessary for
      aspalatone and ASA to prolong the bleeding time significantly. On the other hand,
      salicylic acid maltol ester which lacks the acetyl group did not significantly
      affect bleeding time at a dose of 15 mg/kg. Aspalatone produced a potent
      inhibition of collagen-induced platelet aggregation in vitro with IC50 of 1.8 x
      10(-4) mol/l, but, similar to ASA, did not significantly inhibit ADP-induced
      aggregation. The ability of oral aspalatone to inhibit platelet aggregation in
      rats ex vivo was compared with other reference antiplatelet drugs. Relative
      potency was ASA > dipyridamole approximately equal to aspalatone > ticlopidine. A
      single dose of aspalatone potently prevented death due to collagen-induced
      platelet aggregation in mice in vivo with ED50 value of 32 mg/kg p.o., but failed
      to prevent death due to ADP-induced platelet aggregation. When given for 10 days,
      aspalatone prevented collagen-induced death by 90% (p < 0.001) at 20 mg/kg, and
      this antithrombotic effect lasted after 4 days of wash-out period.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7818585
TI  - [Comparison of the protective effects of roxatidine and misoprostol on diclofenac
      gastroduodenal pathology. An endoscopic, controlled study of volunteers].
AB  - For prophylaxis of gastroduodenal lesions induced by non-steroidal antirheumatic
      drugs (NSAID) acid-lowering as well as mucosa protective substances are used.
      Direct comparison of both therapeutic regimens are lacking. In randomized
      parallel studies the gastroduodenal tolerability of 100 mg diclofenac daily in
      slow-release form was evaluated in the presence and absence of 150 mg roxatidine
      (CAS 78273-80-0) daily as well as in the presence of 75 mg bid roxatidine or 200
      micrograms bid misoprostol (CAS 59122-46-2). The drugs were taken over a period
      of 14 days. Endoscopic controls were performed at entry, as well as after 14 days
      of treatment. A quantitative damaging score was used. Study A: Both treatment
      groups (n = 20) had at entry comparable mucosal damages: placebo/diclofenac: 0.9
      +/- 0.1 (+/- SEM), roxatidine/diclofenac: 0.9 +/- 0.1; after 14 days of treatment
      the score increased in the diclofenac/placebo group to 7.6 +/- 1.9 and, in the
      corresponding diclofenac/roxatidine group, only to 2.1 +/- 0.9. The difference
      between the two treatment groups after 14 days was significant (p < 0.05). Study
      B: Both treatment groups (n = 24) had comparable mucosal damages at entry:
      diclofenac/roxatidine: 0.9 +/- 0.1, diclofenac/misoprostol: 0.8 +/- 0.1.
      Following 14 days treatment with 100 mg diclofenac daily the damaging score in
      both group rose to comparable levels: roxatidine group 2.1 +/- 0.7 and
      misoprostol group 2.0 +/- 0.4 (n.s.). The data suggest that for prophylaxis of
      NSAID-induced gastroduodenal lesions substances with different mechanism of
      action can be used. The findings underline the complex way by which NSAID can
      damage the mucosa of the upper gastrointestinal tract.

PMID- 7818586
TI  - Ranitidine in the treatment of non-ulcer dyspepsia. A placebo-controlled study in
      the Federal Republic of Germany.
AB  - The trial randomly assigned 652 patients with non-ulcer dyspepsia (NUD), defined
      as chronic or recurrent complaints of acid-related (heartburn, acid
      regurgitation, epigastric pain) and non-acid related (fullness/vomiting, nausea)
      symptoms and with no evidence of organic disease, to treatment for 4 weeks with
      150 mg of ranitidine (Zantic, CAS 66357-59-3) twice a day, or placebo, according
      to a double-blind design. The presence and duration of all dyspeptic symptoms
      were recorded by interviews at the beginning and after 2 and 4 weeks of treatment
      as well as by diaries. The complete disappearance of all dyspeptic symptoms after
      4 weeks in the placebo group was 36%; ranitidine treatment resulted in a
      significant improvement after 4 weeks (p < 0.05). The effect of ranitidine was
      slightly more pronounced in acid-related than in non-acid-related symptoms. We
      conclude that suppression of gastric acid secretion is of clinical value in NUD
      patients, especially in those suffering from epigastric pain, acid regurgitation
      and heartburn.

PMID- 7818587
TI  - Glycogenic effect of an alkali soluble fraction from sepia shell.
AB  - The alkali soluble fraction of the sepia shell possesses both anticonvulsant and
      hypoglycemic effect. The investigation regarding the fate of the blood sugar
      during the hypoglycemia revealed that the sepia shell extract acts as a
      glycogenic agent by mobilising the blood sugar towards liver glycogen reserve
      through the modulation of the enzymes glycogen phosphorylase a and ab in normal
      and streptozotocin diabetic mice. The glucose tolerance test (GTT) showed a
      depression in the GTT curve in experimental mice. The available literature on the
      biochemistry of the shell reveals that it contains glucosamines and some amino
      acid residues. The presence of amine group may resemble the sulfonylureas like
      tolbutamide which also possesses both anticonvulsant and hypoglycemic effect.

PMID- 7818588
TI  - Tolerability, pharmacokinetics and dose linearity of azelastine hydrochloride in
      healthy subjects.
AB  - In a double-blind, randomized, 4-period crossover study, single oral doses of
      azelastine hydrochloride tablets (A-05610, Allergodil, Radethazin, Azeptin, CAS
      79307-93-0) were ingested by 12 healthy volunteers (6 males, 6 females, mean age
      25.2 +/- 3.5 years). Dose linearity was demonstrated for 2.2, 4.4, 8.8 and 17.6
      mg of azelastine hydrochloride. The values of AUC0-infinity and Cmax increased
      linear to the dose (means of AUC0-infinity: 47.3, 93.7, 208.0 and 405.90 ng-eq
      h/ml; means of Cmax: 1.5, 3.3, 6.0 and 12.5 ng-eq/ml), whereas tmax and the
      terminal half-life of elimination (t1/2 beta) were obviously not influenced by
      the dose. Mean values over all doses and subjects amounted to 4.6 h (tmax) and
      25.5 h (t1/2 beta). Plasma levels showed relatively high inter- and somewhat less
      intraindividual variations. This is most likely due to a varying degree of
      enterohepatic circulation resulting from alimentary factors. As for the co
      detection of azelastine and the pharmacodynamically active metabolite N-desmethyl
      azelastine by the radio-immuno-assay (RIA) used, the parameters describe the
      pharmacokinetic behaviour as a resultant from both compounds and thus the active
      principle of the drug. Independently of the dosages administered the overall
      tolerance proved to be very good. According to this trial the therapeutic range
      is wide enough to recommend 4.4 mg b.i.d. or single doses of 8.8 mg of azelastine
      hydrochloride per day for therapy in adult patients.

PMID- 7818589
TI  - Synthesis and analgesic activity of new phencyclidine derivatives.
AB  - New phencyclidine derivatives having structural similarities with the well known
      4-phenylpiperidine narcotic analgesics were synthesized characterized and their
      anti-nociceptive activity tested in mice by the hot-plate and tail-flick tests.
      Structure-activity relationships for these compounds further point to the
      importance of a second aryl moiety at position 4 of the piperidine ring of
      phencyclidine. In addition, the presence of a hydroxyl group in close proximate
      to the lipophilic moiety is vital for analgesic activity.

PMID- 7818590
TI  - Thymopentin treatment of rheumatoid arthritis.
AB  - Although the etiology of rheumatoid arthritis (RA) is unknown, there is solid
      evidence that immunological factors play a pivotal role in its pathogenesis. It
      seems that a hyporeactivity of local (intraarticular) T-suppressor cells would
      permit an excessive immune response that ultimately leads to the classical
      symptoms and signs of inflammation and cartilage damage. Thymopentin is a
      synthetic pentapeptide (Arg-Lys-Asp-Val-Tyr) which represents the active biologic
      site (sequence 32-36) of the native thymic hormone thymopoietin, containing 49
      amino acids. Thymopoietin and thymopentin have been shown to possess immuno
      normalizing properties in a number of animal model systems. Low concentrations of
      the hormone characteristically stimulate the OKT4-positive cells, whereas higher
      concentrations additionally induce stimulation of OKT8-positive cells. This
      report summarizes the clinical experience collected by Italian investigators, and
      discusses the results with a view to previously published papers.

PMID- 7818591
TI  - Effect of spironolactone on dimethyl mercury toxicity. A possible molecular
      mechanism.
AB  - The protective activity of spironolactone (CAS 52-01-7) against dimethyl mercury
      intoxication was studied. Dimethyl mercury increased serum glutamate pyruvate
      transaminase (SGPT), serum bilirubin, blood urea nitrogen (BUN), and caused
      impairment of the drug metabolic activity of rat liver in vivo and in vitro. It
      also caused a severe neuropathy to these animals. Administration of
      spironolactone caused a reduction of dimethyl mercury toxicity. It decreased the
      values of SGPT, bilirubin and BUN, and restored the impaired drug metabolism
      caused by dimethyl mercury. The neuropathy produced after administration of
      dimethyl mercury was only mildly ameliorated by the treatment with
      spironolactone. Pregnenolone-16 alpha-carbonitrile (PCN), a potent microsomal
      enzyme inducer, had only a weak action, with the expected exception of the repair
      of the impaired drug metabolism of the liver. A mechanism of the protective
      action of spironolactone against dimethyl mercury intoxication is proposed. It is
      suggested that both the ability to induce drug metabolizing enzymes, here
      demethylases, and the capacity to bind to the demethylated metabolite of the
      organic mercurial, giving a non toxic, easily excretable complex should coexist
      in the protective molecule.

PMID- 7818592
TI  - Effect of fluvastatin sodium on secretion of very low density lipoprotein and
      serum cholesterol levels. In vivo study using low density lipoprotein receptor
      deficient watanabe heritable hyperlipidemic rabbits.
AB  - The hypolipidemic effects of fluvastatin sodium (XU 62-320, CAS 93957-55-2), a
      new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, were examined.
      Fluvastatin sodium was administered to Watanabe heritable hyperlipidemic (WHHL)
      rabbits, a low density lipoprotein (LDL) receptor deficient animal model, for 6
      weeks at doses of 12.5 mg/kg, 25 mg/kg, and 50 mg/kg. Total cholesterol levels in
      serum, in very low density lipoproteins (VLDL), in intermediate density
      lipoprotein, and in LDL decreased dose-dependently. In the 50 mg/kg group,
      cholesterol reduction in each of the aforementioned segments was 50%, 91%, 94%
      and 33%, respectively. The secretion rate of VLDL-cholesterol, as determined by
      intravenous injection of Triton WR-1339, also decreased in a dose-dependent
      manner, showing a reduction of 16% (p < 0.05) in the 50 mg/kg group. In addition,
      the cholesterol content of newly-secreted VLDL also decreased dose-dependently.
      These results indicate that fluvastatin sodium has a potent hypolipidemic effect,
      and suggest that one of the mechanisms responsible for the reduction of serum
      cholesterol may be the suppression of VLDL-cholesterol secretion.

PMID- 7818593
TI  - Activity of 4-quinolones against Pseudomonas aeruginosa.
AB  - The minimum inhibitory concentrations (MICs), bactericidal activities and
      mechanisms of action of ofloxacin (CAS 82419-36-1), levofloxacin (CAS 100986-85
      4) and ciprofloxacin (CAS 86393-32-0) were investigated against Pseudomonas
      aeruginosa. All three 4-quinolones were found to possess higher MICs against
      Pseudomonas aeruginosa than against other Gram-negative bacteria. Despite this,
      however, all three drugs were more rapidly bactericidal and produced a greater
      level of kill against Pseudomonas aeruginosa than against any other bacterial
      species previously tested. Thus MIC tests cannot be used to predict the
      bactericidal activity of 4-quinolones. Furthermore, MIC tests showed
      ciprofloxacin to be more potent than ofloxacin or levofloxacin against
      Pseudomonas aeruginosa. However, bactericidal tests showed levofloxacin to be
      about 10 times more bactericidal than either ciprofloxacin or ofloxacin. Thus MIC
      tests cannot predict the relative bactericidal potency of 4-quinolones against
      Pseudomonas aeruginosa. Therefore, MIC tests should not be used as the sole
      measure for the efficacy of 4-quinolones, as is often the case. Surprisingly, the
      characteristic biphasic dose response curve, normally shown by 4-quinolones
      against other bacteria, was absent when Pseudomonas aeruginosa was tested. This
      unusual effect was explained by the presence of bactericidal mechanism B
      associated with the unique loss of bactericidal mechanism A at high 4-quinolone
      concentrations. This loss of bactericidal mechanism A may explain the recent high
      incidences of chromosomally-mediated 4-quinolone resistance with Pseudomonas
      aeruginosa because it may be easier for Pseudomonas aeruginosa to mutate to
      resist one mechanism of action than to mutate to resist two or more mechanisms of
      action.

PMID- 7818594
TI  - On definition and use of the term bioavailability.
AB  - In common usage, the rate of absorption of an active ingredient or its
      therapeutic moiety is generally not mentioned in the context of bioavailability.
      In this communication it is shown that exclusion of the rate of absorption may
      have serious consequence on the interpretation of bioavailability depending on
      the underlying model for the system under study. In the case of endogenous
      substances, the term "bioavailability" is ambiguous unless one specifies whether
      it refers to availability of the exogenous substance only or the sum total of the
      exogenous and endogenous substances.

PMID- 7818595
TI  - Mast cell distribution in mice.
AB  - A survey on the distribution of mast cells in mice was carried out. Mast cells
      were present in abundance in tongue and to a lesser extent in sciatic nerve.
      Fewer numbers of mast cells were seen in lymph nodes, e.g. cervical, pararenal
      and iliac. Mast cells were not common in mesenteric lymph nodes in contrast to
      rats. Mast cells appeared to be widely distributed in different organs, e.g.
      salivary gland, cervix, vagina, uterus, epididymides, skeletal, muscle, ovaries,
      prostate, seminal vesicles, harderian glands, skin, adipose tissue, preputial
      gland, tail, urinary bladder, trachea, thymus and gall bladder. Mast cells were
      very few in heart, liver, bone marrow and lungs and generally fewer than in rats.
      Mast cells were very rare in spleen and adrenals. Scattered individual mast cells
      were occasionally seen in submucosa and serosa of stomach, oesophagus, small and
      large intestine. Mast cells were not seen in kidney, pituitary, testes, bone,
      spinal cord, brain, optic nerve and eyes. In lymph nodes mast cells appeared
      mainly in medullary sinusoids. There was no clear evidence of a difference
      between numbers of mast cells in animals of different age or sex. There was
      evidence of increased numbers of mast cells in inflammatory lesions and in cases
      of malignant tumours such as lymphomas. Presence of mast cells is incidental and
      is not indicative of any abnormalities.

PMID- 7818596
TI  - Medicaid increases the burden on state budgets.

PMID- 7818597
TI  - Federal health reform--what happened?

PMID- 7818598
TI  - Creativity plus activism equals a formula for managing change.

PMID- 7818599
TI  - Social issues distract.

PMID- 7818600
TI  - Social issues distract.

PMID- 7818601
TI  - Which language for deaf children?

PMID- 7818604
TI  - Joint Committee on Infant Hearing. 1994 position statement.

PMID- 7818603
TI  - Five-year curriculum for the preparation of speech-language pathologists.

PMID- 7818602
TI  - Face to FASCE with strangers. The challenge of cultural diversity.

PMID- 7818605
TI  - Credit where credit is due.

PMID- 7818606
TI  - Otosclerosis.

PMID- 7818607
TI  - Unexplained bradycardia during craniotomy closure: the role of intracranial
      hypotension.

PMID- 7818608
TI  - Obex/nucleus gracilis position: its role as a marker for the cervicomedullary
      junction.
AB  - Traditionally, the decussation for the pyramids has been the designated marker
      for the cervicomedullary junction. With Chiari malformations abnormal caudal
      migration of posterior fossa structures occurs, resulting invariably in a low
      position of the caudal poles of the cerebellar tonsils (i.e. tonsillar
      heterotopia) and a low position of the cervicomedullary junction. Since there is
      considerable variability in normal caudal tonsillar position and because the
      pyramidal decussations are difficult to image, diagnostic confusion may exist
      when the cerebellar tonsils reside in an intermediately low position. This study
      utilized anatomic specimens to establish the normal morphologic relationship
      between the position of the obex/nucleus gracilis (O/NG) and the pyramidal
      decussations; the former consistently lies 5-6 mm rostral to the latter. Having
      established that anatomic relationship, the O/NG position was then used to assess
      the cervicomedullary junction position in a radioanatomic survey of normal brain
      MR examinations. This analysis established a mean O/NG position 10-12 mm above
      the plane of the foramen magnum. The O/NG position was then evaluated in patients
      with low tonsillar position. This analysis revealed, as expected, that patients
      with Chiari II malformation exhibited tonsillar and O/NG positions well below the
      plane of the foramen magnum. It also distinguished between two additional groups
      of patients with less florid MR findings. These include patients who exhibit
      minimally low cerebellar tonsils but essentially normal O/NG position; these
      patients should be considered normal expressing only minor variation of tonsillar
      position. The remaining patients exhibit evidence of both intermediately low
      tonsillar and low O/NG positions, suggesting an underlying anomaly of both tonsil
      and brainstem development.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7818609
TI  - Postpartum bilateral renal vein thrombosis in the primary antiphospholipid
      syndrome.
AB  - A young Caucasian woman developed bilateral deep vein thromboses (DVT) while
      taking the oral contraceptive (OC) in 1984. After a 9-month period of longterm
      anticoagulation therapy with warfarin, she experienced recurrent DVT 2 weeks
      following discontinuation of anticoagulation. She was then maintained with
      warfarin for the following 6 years. Elevated antibodies to cardiolipin (IgG aCL)
      were first detected in 1988. In 1990, warfarin was switched to aspirin and low
      molecular weight heparin as she wished to become pregnant. At 24 weeks she
      developed eclampsia and labor was induced. During the first postpartum week she
      experienced loin pain, associated with rapidly rising creatinine levels and
      features of a nephrotic syndrome. An abdominal ultrasound showed bilateral renal
      vein thrombosis with enlarged kidneys. She was treated with continuous ambulatory
      peritoneal dialysis (CAPD) for 4 months and her renal function is now recovering.
      Our patient is another example of the primary antiphospholipid syndrome.

PMID- 7818610
TI  - A twenty-year retrospective analysis of the efficacy of epidural analgesia
      anesthesia when administered and/or managed by obstetricians.
AB  - OBJECTIVE: The purpose of this study was to retrospectively determine the safety
      and efficacy of epidural anesthesia when administered by obstetricians in a
      community hospital. STUDY DESIGN: Data containing 14,598 epidural procedures from
      31,818 births were obtained from delivery room logs over a period of 20 years,
      from 1972 through 1991. Data were displayed graphically to view trends over time.
      Odds ratios were calculated to determine the associations of epidural anesthesia
      with oxytocin stimulation, episiotomy, assisted vaginal delivery (forceps or
      vacuum extraction), and cesarean section. Particular scrutiny was given to any
      listed complication during labor or delivery. RESULTS: Over the 20-year period
      epidural anesthesia was administered without serious complication by various
      obstetricians with different training. Technique improved as procedures became
      standardized, resulting in an increase in the number of epidural procedures over
      the 20-year period. Incidence was also increased among women requiring oxytocin
      augmentation, episiotomies, and assisted vaginal deliveries. Of the total number
      performed, < 5% of patients required additional anesthesia. CONCLUSION: Over a 20
      year period epidural analgesia or anesthesia has been an effective and safe
      procedure when performed and supervised by obstetricians-gynecologists in a
      community hospital.

PMID- 7818611
TI  - Tissue reaction to expanded polytetrafluoroethylene suburethral sling for urinary
      incontinence: clinical and histologic study.
AB  - OBJECTIVE: The use of expanded polytetrafluoroethylene suburethral sling for
      recurrent urinary incontinence has shown an excellent cure rate but a number of
      complications. This study was designed to evaluate patients who had tissue
      reaction or removal of the sling, to determine potential causes, clinical course,
      and eventual outcome. STUDY DESIGN: A retrospective review of consecutive charts
      was completed for 115 patients who had suburethral sling surgery with expanded
      polytetrafluoroethylene. Patients having tissue reaction or removal of sling
      material were identified, and eight removed sling specimens were analyzed
      histologically with Milligan's trichrome, hematoxylin and eosin, fibrin, Brown
      Brenn bacteria, and Dahl's calcium stains. RESULTS: Twenty-four patients had
      reactions to the sling material, and 23 slings were eventually removed. Seventeen
      of 23 patients having sling removal remained continent. Histologic evaluations
      revealed gram-positive cocci in all expanded polytetrafluoroethylene patch
      interstices. Fibrous tissue, fibroblasts, and collagen were present in one half
      of specimens. CONCLUSION: There is a 23% reaction or removal rate for expanded
      polytetrafluoroethylene suburethral sling procedures. Seventeen of 23 patients
      remained continent in spite of sling removal. Histologic studies showed gram
      positive cocci in the patch interstices, although prophylactic antibiotic
      coverage did not prevent infection and cultures from the vaginal or abdominal
      reaction sites did not reveal a significant growth of organisms. Patients need to
      be aware of the high complication rate for this suburethral sling procedure, and
      physicians need to work further to modify sling materials and techniques to
      reduce complications.

PMID- 7818613
TI  - Move over, George Orwell--things are stranger in 1993.

PMID- 7818612
TI  - Structure-function analysis of antimicrotubule dinitroanilines against
      promastigotes of the parasitic protozoan Leishmania mexicana.
AB  - Although leishmaniasis is a major tropical disease, the currently available drugs
      are toxic and inadequate. We show that the antimicrotubule herbicide trifluralin
      has antileishmania activity. The present study aimed at deducing the relationship
      between the structure of the molecule and its antiprotozoan activity. Nine
      dinitroanilines, all of which were analogs of trifluralin, were compared. We
      found that pendimethalin was 2.5-fold more potent than trifluralin, and the
      higher efficacy may be correlated with molecular structural features that
      increase the accessibility to one nitro group. This association was further
      supported by molecular modeling. Moreover, trifluralin samples from two sources
      differed in their activities by more than threefold, and gas column
      chromatography showed that impurities were present in the more potent sample.

PMID- 7818614
TI  - Clinical rules for phenytoin dosing.
AB  - OBJECTIVE: To develop simple clinical rules for dosing phenytoin (PHT) using
      computer simulations, then to test the rules for accuracy and safety on actual
      patient data. DESIGN: Patients with steady-state PHT plasma concentrations at
      least two different PHT doses were identified from three separate sources of
      patient data. A computerized dosing program calculated pharmacokinetic parameters
      using Bayesian methodology, then predicted how many patients were likely to reach
      potentially toxic PHT plasma concentrations when their daily dosage was increased
      by 30, 50, or 100 mg. Dosing rules were developed to allow fewer than ten percent
      of resultant plasma concentrations to exceed 25 micrograms/mL. The dosing rules
      then were tested on dose/plasma concentration data from a separate group of
      patients. SETTING: All patients were being treated by neurologists either as
      outpatients or inpatients. PATIENTS: All patients were adults with epilepsy being
      treated with PHT; none had clinically significant renal or hepatic disease.
      Patients for the computer simulation were from three sources: (1) patients who
      had an initial PHT plasma concentration < 10 micrograms/mL and required a dosage
      increase; (2) patients admitted to the hospital for PHT intoxication; and (3)
      patients who required consultations specifically for PHT dosing. Patients on whom
      the dosing rules were tested were part of a prospective, randomized trial of
      antiepileptic drug safety and efficacy. MAIN OUTCOME MEASURES: Successful dosing
      rules allowing fewer than ten percent of resulting plasma concentrations in the
      test group to exceed 25 micrograms/mL. RESULTS: The simulations used 167 actual
      dose/plasma concentration pairs from 45 patients. The resulting dosing rules
      were: increase the dosage by 100 mg/d if the initial plasma concentration was < 7
      micrograms/mL; increase the dosage by 50 mg/d if the initial plasma concentration
      is 7 to < 12 micrograms/mL; increase the dosage by 30 mg/d if the initial plasma
      concentration is > or = 12 micrograms/mL. The rules were tested on 129 50- or 100
      mg dosage increases in 77 patients. All 53 dosage increases that were within the
      dosing rules produced plasma concentrations < 25 micrograms/mL, whereas 36
      percent (27 of 74) of the dosage increases that exceeded the dosing rules
      produced plasma concentrations > 25 micrograms/mL. CONCLUSIONS: The proposed
      dosing rules are a simple method for clinicians to estimate PHT dosage changes
      and appear to be safe and accurate when applied retrospectively to actual patient
      data.

PMID- 7818615
TI  - Building an effective therapeutic alliance: competence, trustworthiness, and
      caring.
AB  - Patient counseling and pharmaceutical care require much more than the provision
      of information. They require a commitment on the part of the pharmacist to the
      well-being of the patient. They also require the formation of a therapeutic
      alliance. Patients are not likely to tell pharmacists about problems they have in
      managing their drug therapy if they believe they will be judged or scolded for
      nonadherence. Patients must feel safe enough to present problems or ask
      questions. In responding to how patients manage their illnesses and interpret the
      pharmacists' instructions, pharmacists must treat each patient as unique.
      Pharmacists must develop a flexible system of response. What is comforting to one
      patient might be frightening to another. By developing a flexible system of
      response, pharmacists will be able to treat patients more effectively. There are
      no right or wrong answers, only those that work. A pharmacist's basic
      understanding and true desire to care for the patient will increase the number of
      successful responses.

PMID- 7818617
TI  - Intraarticular pathology in acute, first-time anterior shoulder dislocation: an
      arthroscopic study.
AB  - Intraarticular soft tissue damage after first-time, acute shoulder dislocation
      has been poorly described in the literature. The present study describes 24 cases
      of first-time anterior shoulder dislocation that all were evaluated under
      anesthesia and examined via arthroscopy. All shoulders sustaining anterior
      dislocation show Bankart and Hill-Sachs lesions. They also show anterior
      instability. The arthroscopic findings were uniform and therefore cannot be used
      as predictors for future development of recurrent instability.

PMID- 7818616
TI  - Quality of life in Norwegian kidney donors.
AB  - The Norwegian kidney transplant programme is based on more extensive use of
      living donors than in other countries. Re-examination of the physical health of
      kidney donors has in the majority of studies revealed no long-term medical risk.
      The quality of life after donation has only been described in very few studies,
      and with a small number of donors. This report concerns a cross-sectional study
      of 494 donors with a mean observation time from donation of 6.7 years. A
      standardized questionnaire containing 19 items related to quality of life was
      used. The donors were compared to the general adult population in a county in mid
      Norway. Out of the 19 quality of life items, the donors scored significantly
      better in 13. Donors who had experienced that the corresponding recipient had
      died have been tested separately. The results in this subgroup were equal to the
      population, but inferior compared to the rest of the donors. We conclude that the
      quality of life of Norwegian kidney donors is better than the general population.
      We will continue our policy of an extensive use of living kidney donors.

PMID- 7818618
TI  - Dermis-fat graft after parotidectomy to prevent Frey's syndrome and the concave
      deformity.
AB  - Dermis-fat grafts were performed on 7 patients at the time of parotidectomy to
      prevent Frey's syndrome and the characteristic concave deformity. Only 1 patient
      demonstrated postoperative Frey's syndrome, and 1 demonstrated a slightly concave
      deformity due to fat absorption. Although other barrier materials have been
      reported to achieve success in preventing gustatory sweating, our method
      simultaneously corrects the associated deformity of facial contour as well.

PMID- 7818619
TI  - An epidemic of childhood diabetes in the United States? Evidence from Allegheny
      County, Pennsylvania. Pittsburgh Diabetes Epidemiology Research Group.
AB  - OBJECTIVE: To evaluate IDDM trends in Allegheny County, Pennsylvania, from 1965
      to 1989. RESEARCH DESIGN AND METHODS: A population-based registry established in
      1976--the Allegheny County Registry--was used for this study through a
      retrospective chart review of all cases diagnosed in the county from 1965.
      Through this registry, cases of IDDM patients < 20 yr of age were identified. In
      addition, pediatricians in the county were contacted about IDDM cases they
      diagnosed between 1965 and 1989 in individuals < 20 yr of age. RESULTS: For the
      first time a major increase in IDDM was seen (1985-1989). This increase in IDDM
      was heterogenous with the rise for males being double that for females. The
      increase for non-white males was considerably greater than that seen for white
      males, and an exceptionally large increase in the youngest age-group (0-4 yr of
      age) was observed. CONCLUSIONS: Ecological analyses indicated an association
      between chicken pox infection and IDDM, and this suggested that at least part of
      the rise may be of an infectious origin.

PMID- 7818620
TI  - The acute pediatric scrotum.
AB  - The acute pediatric scrotum is a common clinical condition that can present a
      diagnostic dilemma for even the most experienced physician. The issue of primary
      importance in each case is to ensure testicular viability through proper
      evaluation, prompt diagnosis, and surgical intervention if necessary. A review of
      the various etiologies of acute scrotal disorders in children aids in the
      formulation of a logical and systematic approach to their accurate diagnosis and
      management.

PMID- 7818621
TI  - Unusual coronary patterns and arterial switch outcome.

PMID- 7818622
TI  - An initial multicenter, randomized controlled trial on the safety and efficacy of
      acadesine in patients undergoing coronary artery bypass graft surgery. SPI
      Research Group.
AB  - Acadesine (5-amino-4-imidazole carboxamide riboside) is a purine nucleoside
      analog that has been shown in animals to reduce myocardial ischemic injury by
      selectively increasing the availability of adenosine in ischemic tissues. Because
      patients undergoing coronary artery bypass graft (CABG) surgery are especially
      vulnerable to developing myocardial ischemia, we investigated whether
      perioperative use of this adenosine-regulating drug with potential anti-ischemic
      properties could modify the incidence and severity of perioperative myocardial
      ischemia. The goals of this study were to evaluate safety and the effects of
      acadesine on myocardial ischemia, left ventricular function, and, secondarily, on
      adverse clinical outcomes (myocardial infarction, heart failure, life-threatening
      dysrhythmias, and death) in patients undergoing CABG surgery. One hundred sixteen
      patients were randomized to receive one of three continuous intravenous dosing
      regimens (placebo [control] or one of two doses of acadesine [high- and low-dose
      infusion]) in double-blind fashion intraoperatively and in the early
      postoperative period (total infusion time was 7 h). Multidose cold crystalloid
      cardioplegia (each containing either acadesine or placebo) was used for
      myocardial protection. All were monitored for potentially drug-related adverse
      events and the presence of myocardial ischemia was assessed by continuous Holter
      electrocardiography (ECG) and transesophageal echocardiography (TEE). All
      patients received standardized anesthetic, surgical, and hemodynamic management
      during the intraoperative period. All research data (ECG, TEE, outcome data) were
      evaluated at the coordinating center (San Francisco) in blinded fashion to ensure
      that uniform data analysis criteria were employed. The administration of
      acadesine was safe: mild increases in plasma uric acid (a metabolite of
      acadesine) occurred only in patients receiving high doses (mean increase 1.6 +/-
      0.2 mg/dL) and were without clinical sequelae. Before drug administration in the
      preoperative period (baseline), the incidence and severity of ECG ischemia did
      not differ among the three groups (placebo = 18%; low-dose = 14%; high-dose =
      14%). During prebypass, the incidence of ECG ischemia was similar in all three
      groups (0%, 3%, 3%, respectively). The incidence of TEE ischemia was numerically
      lower in the two acadesine groups (high-dose = 6%, low-dose = 15%) than in the
      control group (19%), but this was not statistically significant (P = 0.22).
      During postbypass, the incidence of ECG ischemia was 11% in the high-dose group,
      22% in the low-dose group, and 18% in the control group (P = 0.42), and TEE
      ischemia was similar in incidence in all groups (placebo = 29%; low dose = 27%;
      high-dose = 24%) (P = 0.86).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7818623
TI  - Eutectic mixture of local anesthetics (EMLA) cream.

PMID- 7818624
TI  - Monitoring for anthracycline cardiotoxicity.
AB  - OBJECTIVE: To review the basis for recommendations of the Cardiology Committee of
      the Children's Cancer Study Group, published in Pediatrics, for serial cardiac
      monitoring of cancer patients during anthracycline therapy and reduction of
      therapy should cardiac studies show abnormalities. DESIGN: Because the effects of
      overall morbidity and mortality should be considered when a recommendation is
      made to withhold potentially lifesaving chemotherapy based on abnormal cardiac
      findings of patients without clinical evidence of cardiac dysfunction, supporting
      studies referenced in the published recommendations were reviewed. Specifically,
      studies were evaluated to determine whether a reduction in anthracycline dose, as
      a result of abnormal cardiac findings by monitoring, reduced cardiac morbidity
      and related mortality compared with a prospectively followed control population
      without dose modification. In addition, the effects of cardiac monitoring and
      subsequent anthracycline dose modification on oncologic morbidity and mortality
      were reviewed in these studies. Finally, the contributions of the cardiac and
      oncologic effects of dose modification were examined to determine the effect of
      this change in therapy on overall morbidity and mortality. RESULTS: None of the
      studies cited in developing these recommendations prospectively determined, with
      controls, the effects of cardiac monitoring and anthracycline dose modification
      on cardiac, oncologic, or overall morbidity and mortality. Therefore, none of the
      studies cited in support of cardiac monitoring and subsequent dose reduction
      demonstrated the efficacy of such an approach. In the absence of such data,
      concerns are raised as to whether such a monitoring program with subsequent dose
      modification might do more harm than good. In addition, none of the methods of
      screening for anthracycline cardiotoxicity has been shown to be adequately
      predictive of early or late cardiac outcomes. Finally, adoption of these
      recommendations would inhibit the investigation of the efficacy of the proposed
      plan. CONCLUSION: Given the absence of supportive data and the potential to do
      harm, no recommendation for dose modification based on abnormal cardiac findings
      in patients without clinical evidence of cardiotoxicity can be endorsed,
      including those of the Cardiology Committee of the Children's Cancer Study Group.
      When clinical evidence of cardiotoxicity is present, anthracycline dose
      modification is recommended. A prospective controlled study to determine the
      effects of dose modification based on cardiac test results is indicated.

PMID- 7818625
TI  - Images in clinical medicine. Quitter's nail.

PMID- 7818626
TI  - Are there differences among nonsteroidal antiinflammatory drugs? Comparing
      acetylated salicylates, nonacetylated salicylates, and nonacetylated nonsteroidal
      antiinflammatory drugs.

PMID- 7818628
TI  - Balloon or bougie for dilatation of benign esophageal stricture?
AB  - Ninety-three adult patients with benign esophageal stricture were randomized to
      receive balloon or bougie dilatation. Eighty-five patients were eligible for
      analysis and were followed prospectively for a year. Twenty-four patients
      required repeat dilatation within a year, but 50 patients completed a year's
      follow-up without further dilatation. The bougie group initially had a better
      symptomatic result, experiencing significantly less dysphagia at five months,
      although this difference had disappeared at one year. Eighteen patients in the
      balloon group required redilatation for symptoms compared with six in the bougie
      group. The bougie group had a significantly greater increase in their stricture
      diameter, and this was still present at one year after dilatation. There was no
      significant difference in safety or patient acceptability. Balloons are probably
      more costly to use than bougies. Bougie dilatation is to be preferred to balloon
      dilatation in adults except in special circumstances.

PMID- 7818627
TI  - Role of viscous guar gums in lowering the glycemic response after a solid meal.
AB  - The aim of the present study was to investigate how guar gum viscosity acts on
      starch digestion and glucose absorption in humans. Six healthy subjects received
      a mixed diet composed of 60.4% carbohydrate in the form of maize glucose or
      pregelatinized starch, to which was added 5.6% low- or high-viscosity guar gums.
      Meals were ingested or instilled in the duodenum and postprandial insulin and
      glucose responses were monitored for 3 h. Infusion of meals containing glucose
      showed that the delay in the diffusion rate to the duodenal mucosa due to bolus
      viscosity was not significant. Infusion of meals containing starch showed that a
      decrease in the digestion rate of starch in the upper small intestine accounted
      for part of the effect of viscosity on glycemic response, whereas the main effect
      of guar gum was apparently to slow gastric emptying.

PMID- 7818629
TI  - Consensus statement on the triage of critically ill patients. Society of Critical
      Care Medicine Ethics Committee.
AB  - The demand for medical services such as critical care is likely to often exceed
      supply. In the setting of these constraining conditions, institutions and
      individual providers of critical care must use some moral framework for
      distributing the available resources efficiently and equitably. Guidelines are
      therefore provided for triage of critically ill patients. There are several
      general principles that should guide decision making: providers should advocate
      for patients; members of the provider team should collaborate; care must be
      restricted in an equitable system; decisions to give care should be based on
      expected benefit; mechanisms for alternative care should be planned; explicit
      policies should be written; prior public notification is necessary. Patients who
      are not expected to benefit from intensive care, such as those with imminently
      fatal illnesses or permanent unconsciousness, should not be placed in the
      intensive care unit. Hospitals should assign individuals the responsibility of
      intensive care triage, and a committee should oversee the performance of this
      responsibility to facilitate the most efficient and equitable use of intensive
      care.

PMID- 7818630
TI  - Firearm violence and public health. Limiting the availability of guns.

PMID- 7818631
TI  - Does asymptomatic bacteriuria predict mortality and does antimicrobial treatment
      reduce mortality in elderly ambulatory women?
AB  - OBJECTIVE: To determine whether asymptomatic bacteriuria in elderly ambulatory
      women is a marker of increased mortality and, if so, whether it is because of an
      association with other determinants of mortality or because asymptomatic
      bacteriuria is itself an independent cause, the removal of which might improve
      longevity. DESIGN: A cohort study and a controlled clinical trial of the effect
      of antimicrobial treatment. SETTING: A geriatric center and 21 continuing care
      retirement communities. PARTICIPANTS: Women without urinary tract catheters.
      MEASUREMENTS: Urine cultures every 6 months (the same organism at 10(5) colony
      forming units or more per mL on two midstream urine specimens defined
      asymptomatic bacteriuria), comorbidity, and mortality. RESULTS: In the
      observational study, infected residents (n = 318) were older, and sicker, and had
      higher mortality (18.7 per 100,000 resident-days) than uninfected residents (n =
      1173; 10.1 per 100,000 resident-days). However, in a multivariate Cox analysis,
      infection was not related to mortality (relative risk, 1.1; P > 0.2), whereas age
      at entry and self-rated health (score 1 [excellent] to 4 [bad or poor]) were
      strong predictors. In the clinical trial, mortality in 166 treated residents
      (13.8 per 100,000 resident-days) was comparable to that of 192 untreated
      residents (15.1 per 100,000 resident-days); the relative rate was 0.92 (95% CI,
      0.57 to 1.47). The cure rates among treated and untreated residents were 82.9%
      and 15.6%, respectively. CONCLUSION: Urinary tract infection was not an
      independent risk factor for mortality, and its treatment did not lower the
      mortality rate. Screening and treatment of asymptomatic bacteriuria in ambulatory
      elderly women to decrease mortality do not appear warranted.

PMID- 7818633
TI  - Medical aspects of the persistent vegetative state (1).
AB  - This consensus statement of the Multi-Society Task Force summarizes current
      knowledge of the medical aspects of the persistent vegetative state in adults and
      children. The vegetative state is a clinical condition of complete unawareness of
      the self and the environment, accompanied by sleep-wake cycles, with either
      complete or partial preservation of hypothalamic and brain-stem autonomic
      functions. In addition, patients in a vegetative state show no evidence of
      sustained, reproducible, purposeful, or voluntary behavioral responses to visual,
      auditory, tactile, or noxious stimuli; show no evidence of language comprehension
      or expression; have bowel and bladder incontinence; and have variably preserved
      cranial-nerve and spinal reflexes. We define persistent vegetative state as a
      vegetative state present one month after acute traumatic or nontraumatic brain
      injury or lasting for at least one month in patients with degenerative or
      metabolic disorders or developmental malformations. The clinical course and
      outcome of a persistent vegetative state depend on its cause. Three categories of
      disorder can cause such a state: acute traumatic and non-traumatic brain
      injuries; degenerative and metabolic brain disorders, and severe congenital
      malformations of the nervous system. Recovery of consciousness from a
      posttraumatic persistent vegetative state is unlikely after 12 months in adults
      and children. Recovery from a nontraumatic persistent vegetative state after
      three months is exceedingly rare in both adults and children. Patients with
      degenerative or metabolic disorders or congenital malformations who remain in a
      persistent vegetative state for several months are unlikely to recover
      consciousness. The life span of adults and children in such a state is
      substantially reduced. For most such patients, life expectancy ranges from 2 to 5
      years; survival beyond 10 years is unusual.

PMID- 7818632
TI  - The clinical efficacy of magnetic resonance imaging in neuroimaging.
AB  - PURPOSE: To assess the clinical efficacy of magnetic resonance imaging (MRI) for
      neuroimaging and to provide guidelines for clinical practice. STUDY SELECTION:
      After a comprehensive literature search, studies of the diagnostic accuracy of
      MRI alone or compared with other tests and of any impact on therapeutic choices
      or patient outcomes were reviewed by independent readers, followed by discussion
      to reach consensus conclusions. DATA EXTRACTION: Of 3125 citations retrieved, 156
      studies with original data could be rated according to methodologic criteria for
      study design. One article contributed grade A quality information about
      diagnostic accuracy, 28 were graded B or C, and 113 were graded D. One randomized
      trial and 2 comparison studies contributed grade B or C information about the
      impact on therapeutic choices. Only 2 studies surveyed health status before and
      after magnetic resonance scanning. RESULTS: For most abnormalities, the
      sensitivity of MRI is equal to or better than competing technologies. Magnetic
      resonance imaging shows greater contrast and detail than computed tomography (CT)
      but also shows more clinically silent abnormalities or incidental findings. A few
      studies found a modest impact on therapeutic choices but no impact on quality of
      life or disability. Costs for MRI are high. Computed tomography is sufficient for
      initial diagnosis of most mass lesions or intracranial hemorrhages requiring
      immediate intervention. Magnetic resonance imaging is more accurate in the
      temporal lobes, posterior fossa, brainstem, and spinal cord. For lumbar
      radiculopathy, MRI and plain spinal CT are as accurate as post-myelographic CT
      and are less invasive. The role of magnetic resonance angiography for carotid
      artery stenosis is being studied. CONCLUSIONS: Although suggestions for
      appropriate use of MRI in clinical practice can be made, the supporting evidence
      in published studies is weak. Firm guidelines for appropriate use of MRI should
      be based on further clinical research using more rigorous methods.

PMID- 7818634
TI  - Pathoanatomic correlation between poststroke pathological crying and damage to
      brain areas involved in serotonergic neurotransmission.
AB  - BACKGROUND AND PURPOSE: The aim of the study was to correlate the severity of
      poststroke pathological crying with lesion size and location. METHODS: Twelve
      selected stroke patients were ranked in terms of overall clinical severity of the
      syndrome of pathological crying, and the size and location of the stroke
      lesion(s) were determined by magnetic resonance imaging. RESULTS: The patients
      with the clinically most severe pathological crying had relatively large
      bilateral pontine lesions without lesions in the hemispheres. The intermediate
      group had bilateral central hemispheric lesions, and the clinically least
      affected patients had mainly unilateral large subcortical lesions. CONCLUSIONS:
      Poststroke pathological crying may be attributable to stroke-induced partial
      destruction of the serotonergic raphe nuclei in the brain stem or their ascending
      projections to the hemispheres.

PMID- 7818635
TI  - An examination of linkage of schizophrenia and schizoaffective disorder to the
      pseudoautosomal region (Xp22.3)
AB  - We investigated linkage between schizophrenia and the loci DXYS14, DXYS17, and
      MIC2 within the pseudoautosomal region in 85 families with two or more siblings
      suffering from schizophrenia or schizoaffective disorder. A maximum lod score of
      2.44 was reached at MIC2, with a dominant model of inheritance at a recombination
      fraction of 0.367 in females and 0.046 in males (a F:M sex ratio > 1, i.e.
      opposite to that expected with a pseudoautosomal locus). Evidence consistent with
      linkage (P = 0.01) was also obtained with a sibling pair analysis at the MIC2
      locus. These data do not support (although they do not definitively exclude) a
      locus within the pseudoautosomal region; they are consistent with the presence of
      a gene that predisposes to schizophrenia in the sex-specific regions of the X and
      Y chromosomes.

PMID- 7818636
TI  - Apolipoprotein E4 and Alzheimer's disease pathology in Lewy body disease and in
      other beta-amyloid-forming diseases.

PMID- 7818637
TI  - Neonatal serologic screening and early treatment for congenital Toxoplasma gondii
      infection. The New England Regional Toxoplasma Working Group.
AB  - BACKGROUND: Most infants with congenital Toxoplasma gondii infection have no
      symptoms at birth, but many will have retinal disease or neurologic abnormalities
      later in life. Early detection and treatment of congenital toxoplasmosis may
      reduce these sequelae. METHODS: In Massachusetts since January 1986, and in New
      Hampshire since July 1988, newborns have been screened for intrauterine infection
      with T. gondii by means of an IgM capture immunoassay of blood specimens
      routinely collected for screening for metabolic disorders. Congenital infection
      is confirmed by assays for specific IgG and IgM antibodies in serum from infants
      and their mothers. For this study, infants with serologic evidence of infection
      underwent extensive clinical evaluation and received one year of treatment.
      RESULTS: Through June 1992, 100 of 635,000 infants tested had positive screening
      tests. Congenital infection was confirmed in 52 infants, 50 of whom were
      identified only through neonatal screening and not through initial clinical
      examination. However, after the serologic results became available, more detailed
      examinations revealed abnormalities of either the central nervous system or the
      retina in 19 of 48 infants evaluated (40 percent). After treatment, only 1 of 46
      children had a neurologic deficit (hemiplegia attributable to a cerebral lesion
      present at birth). Thirty-nine treated children had follow-up ophthalmologic
      examinations when one to six years old; four (10 percent) had eye lesions that
      may have developed postnatally (a macular lesion in one child and minor retinal
      scars in three). CONCLUSIONS: Routine neonatal screening for toxoplasmosis
      identifies congenital infections that are subclinical, and early treatment may
      reduce the severe long-term sequelae.

PMID- 7818638
TI  - Establishing a nicotine threshold for addiction. The implications for tobacco
      regulation.

PMID- 7818639
TI  - Swimming and grommets: a prospective survey.
AB  - AIM: To assess the incidence of otorrhoea after swimming in patients with
      grommets in situ, and discover whether protecting the ears from water affects
      this occurrence. METHODS: A group of children with bilateral patent grommets were
      allowed to swim with head under the water with one ear protected, and the other
      unprotected from water entry. Using a calendar system, each swim was recorded and
      each episode of otalgia or otorrhoea occasioning medical consultation was
      recorded with the outcome of the consultation. RESULTS: Nineteen children
      completed the survey taking a total of 551 swims with head immersion. One child
      suffered bilateral otorrhoea one day after a swim. There were three episodes of
      otalgia sufficiently severe to warrant medical consultation. Two occurred in a
      protected ear and one in an unprotected ear. On each occasion there was no
      evidence of infection. CONCLUSIONS: There appears to be a low incidence of
      otorrhoea during summer in children who swim with grommets in situ. There is no
      evidence that protecting the ears from water entry confers any benefit as far as
      preventing infection in concerned.

PMID- 7818640
TI  - A massive outbreak in Milwaukee of cryptosporidium infection transmitted through
      the public water supply.
AB  - BACKGROUND: Early in the spring of 1993 there was a widespread outbreak of acute
      watery diarrhea among the residents of Milwaukee. METHODS: We investigated the
      two Milwaukee water-treatment plants, gathered data from clinical laboratories on
      the results of tests for enteric pathogens, and examined ice made during the time
      of the outbreak for cryptosporidium oocysts. We surveyed residents with confirmed
      cryptosporidium infection and a sample of those with acute watery diarrhea
      consistent with cryptosporidium infection. To estimate the magnitude of the
      outbreak, we also conducted a survey using randomly selected telephone numbers in
      Milwaukee and four surrounding counties. RESULTS: There were marked increases in
      the turbidity of treated water at the city's southern water-treatment plant from
      March 23 until April 9, when the plant was shut down. Cryptosporidium oocysts
      were identified in water from ice made in southern Milwaukee during these weeks.
      The rates of isolation of other enteric pathogens remained stable, but there was
      more than a 100-fold increase in the rate of isolation of cryptosporidium. The
      median duration of illness was 9 days (range, 1 to 55). The median maximal number
      of stools per day was 12 (range, 1 to 90). Among 285 people surveyed who had
      laboratory-confirmed cryptosporidiosis, the clinical manifestations included
      watery diarrhea (in 93 percent), abdominal cramps (in 84 percent), fever (in 57
      percent), and vomiting (in 48 percent). We estimate that 403,000 people had
      watery diarrhea attributable to this outbreak. CONCLUSIONS: This massive outbreak
      of watery diarrhea was caused by cryptosporidium oocysts that passed through the
      filtration system of one of the city's water-treatment plants. Water-quality
      standards and the testing of patients for cryptosporidium were not adequate to
      detect this outbreak.

PMID- 7818641
TI  - The use of MRI in the diagnosis of occult hip fractures in the elderly: a
      preliminary review.
AB  - Establishing the diagnosis of a non-displaced hip fracture in an elderly patient
      can be a prolonged and costly procedure, involving hospital admission, several
      days of bed rest, and a bone scan 3 to 5 days later. The authors evaluated 10
      hips in 10 patients with a questionable diagnosis of non-displaced hip fracture.
      Magnetic resonance imaging (MRI) soon after admission revealed four patients with
      acute hip fractures who were subsequently treated. The other six patients, whose
      scans were negative for either femoral neck or intertrochanteric fractures, were
      mobilized. The authors show that, through the use of an immediate MRI study of a
      questionable hip fracture, the prolonged recumbency and inherent costs associated
      with awaiting a positive bone scan can be avoided.

PMID- 7818642
TI  - On trust: a basic building block for healing doctor/patient interactions.

PMID- 7818643
TI  - Characteristics of adolescent hallux abducto valgus. A retrospective review.
AB  - The authors review 63 surgical cases of adolescent hallux abducto valgus in 54
      patients from the Foot and Ankle Institute of the Pennsylvania College of
      Podiatric Medicine over a 7-year period. Twenty-five closing base wedge and
      capital osteotomies were evaluated for radiographic changes. Three quarters of a
      group of 65 patients with adolescent hallux abducto valgus were found to have an
      abnormally high metatarsus adductus angle. Patients who had a closing base wedge
      osteotomy had higher preoperative radiographic angles for the intermetatarsal,
      metatarsus adductus, hallux abductus, and proximal articular set angles as well
      as the tibial sesamoid position. Those patients had 4.49 degrees more
      intermetatarsal angle correction than the patients who had a capital osteotomy.
      Implications for evaluation and treatment are discussed.

PMID- 7818644
TI  - Beta carotene, vitamin E, and lung cancer.

PMID- 7818645
TI  - Beta carotene, vitamin E, and lung cancer.

PMID- 7818646
TI  - False positive quitter's nail.

PMID- 7818647
TI  - Anticardiolipin antibodies in an unselected stroke population.
AB  - A pathogenetic role in thrombotic disease, particularly in young people, has been
      postulated for anticardiolipin antibody (ACA). We have carried out a prospective
      controlled study of 262 unselected patients with acute stroke and 226 controls to
      assess the prevalence and relation to age and vascular risk factors of ACA.
      Titres of IgG, IgA, or IgM ACA were above the upper normal limit in 38% of
      patients. The proportions of patients and controls with raised titres did not
      differ significantly (13 vs 8% IgG, 22 vs 29% IgA, 11 vs 7% IgM). IgG titres were
      higher among patients than among controls (mean 3.88 vs 2.86 u/mL [95% CI for
      difference 0.62-0.87], p = 0.0004), whereas IgA and IgM titres were lower in
      patients than in controls (IgA 4.82 vs 5.98 u/mL [1.12-1.60], p = 0.01; IgM 3.00
      vs 3.64 u/mL [1.01-1.45], p = 0.04). However, within age tertiles the only
      significant difference between patients and controls for IgG ACA was in the
      oldest tertile. Analysis by number of risk factors for stroke showed a
      significant difference between the groups only for subjects with one risk factor.
      IgA and IgM ACA titres were higher among controls only in those with no vascular
      risk factors. We found no evidence to support the hypothesis that ACA is an
      independent risk factor for stroke in young people. The increase in IgG titre
      with age and number of vascular risk factors in stroke patients suggests that ACA
      may be a non-specific accompaniment of vascular disease. Routine testing for ACA
      in stroke patients is not justified.

PMID- 7818648
TI  - Effects of low dose versus conventional dose thiazide diuretic on insulin action
      in essential hypertension.
AB  - OBJECTIVE: To see whether low dose thiazide diuretics given to patients with
      essential hypertension might avoid the adverse metabolic consequences seen with
      conventional doses. DESIGN: Double blind randomised crossover study of two 12
      week treatment periods with either low dose (1.25 mg) or conventional dose (5.0
      mg) bendrofluazide given after a six week placebo run in period. SETTING:
      Outpatient clinics serving the greater Belfast area. SUBJECTS: 16 white non
      diabetic patients (9 male) under 65 with essential hypertension recruited from
      general practices within the greater Belfast area. MAIN OUTCOME MEASURES:
      Systolic and diastolic blood pressure and peripheral and hepatic insulin action.
      RESULTS: One man failed to complete the study. There were no differences between
      doses in their effects on systolic and diastolic blood pressure. Bendrofluazide
      1.25 mg had substantially less effect on serum potassium concentration than the
      5.0 mg dose. There were no intertreatment differences in fasting glucose,
      insulin, cholesterol, and triglyceride concentrations. Bendrofluazide 5.0 mg
      significantly increased postabsorptive endogenous glucose production compared
      with baseline (mean 10.9 (SD 1.2) v 10.0 (0.8) mumol/kg/min), whereas
      bendrofluazide 1.25 mg did not. Postabsorptive endogenous glucose production was
      significantly higher with bendrofluazide 5.0 mg compared with 1.25 mg (10.9 (1.2)
      v 9.9 (0.8) mumol/kg/min) but was suppressed to a similar extent after insulin
      (bendrofluazide 5.0 mg 2.8 (1.5) mumol/kg/min v bendrofluazide 1.25 mg 2.2 (1.5)
      mumol/kg/min). Exogenous glucose infusion rates required to maintain euglycaemia
      were not significantly different between doses and were similar to baseline.
      CONCLUSIONS: Bendrofluazide 1.25 mg is as effective as conventional doses but has
      less adverse metabolic effect. In contrast with conventional doses, low dose
      bendrofluazide has no effect on hepatic insulin action. There is no difference
      between low and conventional doses of bendrofluazide in their effect on
      peripheral insulin sensitivity.

PMID- 7818649
TI  - Mother Theresa's care for the dying.

PMID- 7818651
TI  - Clinical judgment.

PMID- 7818650
TI  - Tail docking.

PMID- 7818652
TI  - Promoting research into peer review. Identify referees' institutions.

PMID- 7818653
TI  - Hazards of reducing cholesterol.

PMID- 7818654
TI  - Periocular steroid ointments may cause ocular damage.

PMID- 7818655
TI  - Beta-adrenoceptor blockers in atrial fibrillation: the importance of partial
      agonist activity.

PMID- 7818656
TI  - Comment: enoxaparin--the low-molecular-weight heparin for prevention of
      postoperative thromboembolic complications.

PMID- 7818657
TI  - The question of clarithromycin: a first-line drug for sinusitis?

PMID- 7818658
TI  - Lung volumes and ventilatory flows: report of Working Party.

PMID- 7818659
TI  - Dyskinetic cerebral palsy and birth asphyxia.

PMID- 7818660
TI  - Primary biliary cirrhosis trials and Mayo risk score.

PMID- 7818661
TI  - A patient with primary sclerosing cholangitis ponders pulse: methotrexate paper.

PMID- 7818662
TI  - Firearm violence and public health.

PMID- 7818663
TI  - Firearm violence and public health.

PMID- 7818664
TI  - Anticardiolipin in stroke.

PMID- 7818665
TI  - Preventing biliary stent occlusion.

PMID- 7818666
TI  - Health-care reform issues and role of donors.

PMID- 7818667
TI  - Relation between human papillomavirus type 16 and potential for progression of
      minor-grade cervical disease.

PMID- 7818668
TI  - The brain of Karen Ann Quinlan.

PMID- 7818669
TI  - Withdrawing treatment in the persistent vegetative state.

PMID- 7818670
TI  - DNA fingerprinting dispute laid to rest.
AB  - Two principals in the once-raging debate over forensic DNA typing conclude that
      the scientific issues have all been resolved.

PMID- 7818671
TI  - Transcranial Doppler for emboli.

PMID- 7818672
TI  - The continuing gun debate--puzzling; byzantine and drug abuse?

PMID- 7818673
TI  - Environmental estrogens.

PMID- 7818674
TI  - Extracorporeal carbon chemofiltration under hepatic venous isolation for high
      dose intraarterial chemotherapy of the liver.

PMID- 7818675
TI  - Spontaneous pneumothorax?

PMID- 7818676
TI  - Vaccination against rabies.

PMID- 7818677
TI  - Myocardial infarction and position during sexual intercourse.

PMID- 7818678
TI  - Are ThinPrep smears better than Papanicolaou smears in practice?

PMID- 7818679
TI  - Does the emergency department need a dedicated stat laboratory?

PMID- 7818680
TI  - Storage of lorazepam in polyvinyl chloride bags.

PMID- 7818681
TI  - Use of needle localization for difficult Norplant removal.

PMID- 7818682
TI  - Postimmunization (vaccination) injection-site reactions.

PMID- 7818683
TI  - Put our patients first.

PMID- 7818684
TI  - Intramural coronary artery.

PMID- 7818685
TI  - Decreased heart rate variability in survivors of sudden cardiac death not
      associated with coronary artery disease.

PMID- 7818686
TI  - Controlling the NHS drugs budget. Recommendations may not help.

PMID- 7818687
TI  - Topical steroids for ocular disease.

PMID- 7818688
TI  - Decompression sickness. Role of patent foramen ovale is limited.

PMID- 7818689
TI  - Strength of the genetic effect in schizophrenia.

PMID- 7818690
TI  - HLA-DRB1 antigens in polymyalgia rheumatica.

PMID- 7818691
TI  - IDDM consensus guidelines.

PMID- 7818692
TI  - Blood glucose monitoring for the visually impaired person.

PMID- 7818693
TI  - Somatic dysfunction revisited.

PMID- 7818694
TI  - Effects of closed-head injury on attentional processes: generality of Sternberg's
      additive factor method.
AB  - The present study examined the generality of Shum, McFarland, Bain, and
      Humphreys' (1990) findings that closed-head injury (CHI) selectively impairs
      different processes of attention (operationalized in terms of stages of
      information processing) depending on the severity of, and the time since, injury.
      The procedure of Shum et al. was based on Sternberg's additive factor method
      (AFM), with the mode of information processing involved being a physical
      directional matching of visual stimuli. The present study followed a similar
      procedure except that a name-matching task was used. This task was administered
      to 16 first-year psychology students and two groups of CHI patients (viz., severe
      short-term (SS) and severe long-term (SL)) with matched control groups. The
      results obtained replicated the study by Shum in that the SS group was found to
      be impaired on the identification and response-selection stages of information
      processing whereas the SL group was found to be impaired only on the response
      selection stage. The present study confirms that the AFM is not limited to one
      specific mode of information process and strengthens the validity of the
      conclusions made by Shum et al. regarding the effects of CHI on attention.

PMID- 7818695
TI  - Anticancer antibodies for lung cancer.

PMID- 7818696
TI  - Antiphospholipid antibodies in rheumatic fever chorea.

PMID- 7818697
TI  - Fat necrosis from intramuscular aurothioglucose.

PMID- 7818698
TI  - Efficacy of screening mammography for women in their forties.

PMID- 7818699
TI  - Rationing intensive care.

PMID- 7818700
TI  - Rationing intensive care.

PMID- 7818701
TI  - Treatment of ventricular tachycardia.

PMID- 7818702
TI  - Cholera control among Rwandan refugees in Zaire.

PMID- 7818703
TI  - Apolipoprotein E gene in diffuse Lewy body disease with or without co-existing
      Alzheimer's disease.

PMID- 7818704
TI  - Influence of body mass in endurance cycling.

PMID- 7818705
TI  - Malaria in New Jersey.

PMID- 7818706
TI  - Clinical problem-solving: stopping short of certainty.

PMID- 7818707
TI  - The advantage of rearranging bcl-6.

PMID- 7818708
TI  - Pancreatic cancer and diabetes.

PMID- 7818709
TI  - Drug testing.

PMID- 7818710
TI  - Renal endothelin and hypertension.

PMID- 7818711
TI  - Caution in the interpretation of erythrocyte sedimentation rate in haemodialysis
      and CAPD patients.

PMID- 7818712
TI  - Antineutrophil cytoplasmic autoantibody in two patients with Behcet's disease.

PMID- 7818713
TI  - Use of recombinant erythropoietin in the treatment of anaemia associated with
      multiple myeloma in a haemodialysis patient.

PMID- 7818714
TI  - Recognition of skin cancers.

PMID- 7818715
TI  - Classification.

PMID- 7818716
TI  - Cyriax reexamined.

PMID- 7818717
TI  - The computer and truth.

PMID- 7818718
TI  - Apo E phenotype in atheromatous plaques.

PMID- 7818719
TI  - Perception of needle placement.

PMID- 7818720
TI  - Magnetic resonance imaging of the brain and spine.

PMID- 7818721
TI  - The nature of inquiry: linking quantitative and qualitative research.

PMID- 7818722
TI  - Are dermatologists greedy?

PMID- 7818723
TI  - Technique to reduce air leaks after the resection of emphysematous lung.

PMID- 7818724
TI  - Dietary calcium and plasma lipids.

PMID- 7818725
TI  - Reduction of the acute bioavailability of metformin by the alpha-glucosidase
      inhibitor acarbose in normal man.
AB  - In a double-blind cross-over study, we investigated a possible influence of the
      alpha-glucosidase inhibitor acarbose on the bioavailability of the biguanide
      compound metformin. Each of the six healthy young male volunteers was randomly
      allocated during two consecutive 7 day periods to either acarbose (days 1-3: 3 x
      50 mg day-1; days 4-7: 3 x 100 mg day-1) or placebo. At day 7 and 14 of the
      study, the overnight-fasted subjects ingested 1000 mg metformin with the first
      bite of a standardized breakfast (500 kcal; 60 g carbohydrates) and together with
      either placebo or 100 mg acarbose. Acarbose significantly (P < 0.05) reduced the
      meal-induced increase in blood glucose and plasma insulin levels. Acarbose
      induced a significant (P < 0.05) reduction in early (90, 120, 180 min) serum
      levels, peak concentrations (Cmax: 1.22 +/- 0.14 vs. 1.87 +/- 0.60 mg l-1) and
      area under the curve of metformin (AUC 0-540 min: 423 +/- 55 vs. 652 +/- 55 mg
      min l-1), but did not diminish its 24 h urinary excretion. In conclusion,
      acarbose significantly reduces the acute bioavailability of metformin in normal
      subjects.

PMID- 7818726
TI  - Carbonyl-containing bisphosphonate esters as novel antiinflammatory and
      antiarthritic agents.
AB  - A study of the decomposition of the pyrazoline bisphosphonate ester 2 identified
      3 as the sole bisphosphonate component. Evaluation in a delayed-type
      hypersensitivity granuloma model of chronic inflammation in mice (DTH-GRA) showed
      3 to be a potent inhibitor of granuloma formation (sc, 10 mg/kg, 45%), but in a
      murine model of antigen-induced arthritis (AIA), no significant inhibition was
      observed. As a result, new ketonic bisphosphonate tetraethyl esters were
      synthesized from vinylidenebisphosphonic acid tetraethyl ester 4 and activated
      carbonyl compounds in 13-84% yield. 6 significantly inhibited the pathology of
      both the DTH-GRA (sc, 25 mg/kg, 45%) and AIA models (sc, 25 mg/kg, 55%). Other
      compounds in the series were not as potent. Our results show that bisphosphonate
      ester 6 can inhibit the chronic inflammatory response associated with cutaneous
      granuloma formation and erosive arthritis.

PMID- 7818727
TI  - [Special issue on gastroenterology].

PMID- 7818728
TI  - [Evaluation of the risk of malignant transformation in Barrett esophagus.
      Management before detection of a dysplastic lesion on Barrett's mucosa].

PMID- 7818729
TI  - [Is cancer of the cardia an esophageal cancer or a stomach cancer?].

PMID- 7818730
TI  - [Role of human papillomavirus in esophageal carcinogenesis].

PMID- 7818731
TI  - [Stomach infections in adults].

PMID- 7818733
TI  - [New types of chronic gastritis].

PMID- 7818734
TI  - The small and large intestinal pathologies of non-steroidal anti-inflammatory
      drug ingestion.

PMID- 7818735
TI  - [Intractable infantile diarrhea. A framework to subdivide].

PMID- 7818736
TI  - [Genetic alterations in colorectal cancer].

PMID- 7818732
TI  - [Chronic gastritis associated with Helicobacter pylori in children].

PMID- 7818737
TI  - [Progress on conjunctive tumors of the digestive tube].

PMID- 7818738
TI  - [Digestive manifestations of systemic diseases].

PMID- 7818739
TI  - [Intraoperative monitoring of motor cranial nerves in operations of the neck and
      cranial base].
AB  - Intraoperative monitoring of cranial nerves is performed to minimize
      postoperative cranial nerve dysfunction. We performed electrophysiological
      monitoring of motor cranial nerves with a NIM 2 unit from Xomed Treace and a
      patient multiplexer developed in our clinic. This multiplexer allows simultaneous
      monitoring of 4 cranial nerves and is additionally equipped with a bipolar
      stimulation mode. This intraoperative monitoring was employed during 102 skull
      base operations. Of these 102 operations, 44 were acoustic neuroma removals by
      translabyrinthine approach and 36 by a middle fossa approach. Various operations
      including removal of tumours of the jugular foramen and the infratemporal fossa
      were performed in the remaining 22 patients. The facial nerve, being the most
      frequently monitored nerve, was evaluated both pre- and intraoperatively.
      Electrophysiologic data were evaluated with respect to their predictive value for
      postoperative facial nerve function. The relative per cent decrease in amplitude
      of the EMG after resection compared to that observed before resection seems to be
      of some predictive value for postoperative facial nerve function. A 50-60%
      decrease or more is associated with an increase in the House classification.
      Intraoperative monitoring is a useful tool in skull base surgery allowing for
      safer and faster identification of motor nerves in pathologic anatomic
      conditions. It allows the surgeon a degree of comfort by providing immediate
      information regarding the status of the nerve. It may also improve post-operative
      nerve function and shorten operating time. Additionally, neuromonitoring provides
      some information about expected postoperative facial nerve function.

PMID- 7818740
TI  - [New aspects in surgery of the thyroid gland with intraoperative monitoring of
      the recurrent laryngeal nerve].
AB  - A method for electrophysiological monitoring of the recurrent laryngeal nerve
      during thyroid surgery is described. An electromyographic record from the muscles
      of the vocal folds is obtained using two fine needle electrodes. The electrodes
      are placed endoscopically. The nerve is identified by electrical stimulation, and
      the electromyographic activity is registered using a Nerve Integrity Monitor NIM
      2 (Xomed-Treace). Our experience with this method in 43 patients is described.
      The safety of the integrity of the recurrent laryngeal nerve is increased using
      intraoperative monitoring. This has led to a modification of the operative
      concept in thyroid surgery. Electrophysiological monitoring is mandatory in
      surgery of large goitres, retrotracheal and substernal extension, for re
      operations and malignant diseases of the thyroid gland.

PMID- 7818741
TI  - [The morphology of endonasal cavernous tissue with special reference to muscular
      cushion formation. A light and transmission electron microscopy study].
AB  - Nasal "cavernous" tissue is widely accepted as a key structure for the
      tumefactive mechanism inside the nose; still there is no common understanding of
      the structural composition of this special tissue. In the present paper the
      authors demonstrate the results of their histological and transmission
      electronmicroscopic findings in human nasal "cavernous" tissue, especially
      referring to the structural and ultra-structural pattern of the so-called
      muscular pads or "cushion". Serial sections revealed that these structures occur
      at the transition of communicating vessels; their muscular coat shows a different
      and irregular pattern, compared to the vascular wall structure of other parts of
      nasal "cavernous" tissue. Ultrastructural examination confirmed the impression of
      a variable and complex orientation of smooth muscle cells within the muscular
      "cushions". The cytoplasmic components, however, were the same as in other smooth
      muscle cells of nasal "cavernous" tissue. Localisation and structure of muscular
      "cushions" imply their functional significance for tumescence of the nasal mucosa
      in a variety of rhinological disorders. Therefore, the authors suggest to include
      these special features in therapeutic considerations on the treatment of
      congested nose. Evaluation of the neurovegetative regulation of this tissue could
      be a step in the right direction.

PMID- 7818742
TI  - [Culture of human cartilage tissue using a perfusion chamber].
AB  - In the field of otolaryngology cartilage grafting is commonly performed to
      reconstruct skeletal defects. Knowledge of chondrocyte growth and differentiation
      can now be used to engineer cartilage tissue for grafting. The first condition is
      that chondrocytes maintain their differentiated phenotype besides being able to
      produce a new cartilage matrix. The target of this study was to develop a three
      dimensional culture system for in-vitro formation of vital cartilage transplants.
      Chondrocytes were isolated by digesting the cartilage matrix with collagenase and
      hyaluronidase. After embedding in "low-melting" agarose, the chondrocytes were
      placed into a perfusion culture chamber to provide a constant supply of nutrients
      to the cultures. The peristaltic pump was operated with on/off intervals of 30
      min. Ham's F12 supplemented with 2% FCS and 50 micrograms/ml ascorbic acid was
      employed as culture medium. Monoclonal antibodies specific to collagens type I
      and type II were used to characterise cells and matrix synthesis. Synthesis of
      proteoglycans and collagens was achieved using toluidine blue and azan staining.
      Under the described culture conditions, the chondrocytes maintained a
      differentiated phenotype (expression of collagen type II) with synthesis of
      collagens and proteoglycans. An accumulation of matrix products was achieved
      pericellularly. After 2-8 weeks the obtained tissue exhibited an excellent
      histological appearance showing the typical features of cartilage tissue. The
      results show that the perfusion chamber allows a quick in-vitro fabrication of a
      piece of pure cartilage tissue for transplantation.

PMID- 7818743
TI  - [Nasal positive pressure ventilation (nCPAP) in therapy of obstructive sleep
      apnea: acceptance by 50 patients].
AB  - In a prospective study between 1989 and 1993, 50 patients (45 males, 5 females,
      mean age: 58.4 years; mean AHI = 37.8/h) suffering from obstructive sleep apnoea
      were examined. They underwent nocturnal polysomnography and were provided nightly
      treatment with nasal CPAP (Respironics Sleep-Easy III und REMSTAR, Respironics
      Inc, Monroeville, PA). 41 patients were given primary treatment with nCPAP. Nine
      patients were secondarily treated with a nCPAP mask after other modalities of
      therapy (weight reduction, mandibular positioning appliance, nasal surgery,
      uvulopalatopharyngoplasty) had been applied without success. All patients were
      controlled in the sleep laboratory nine to fourty-two months (mean: 18 months)
      after the masks were fitted. A questionnaire was used to evaluate subjective
      complaints, use of the CPAP mask, technical problems, partner's acceptance of the
      mask etc. 46 patients wore the mask on an average of 6.2 nights per week and 6.5
      hours per night. These self-reported data from the questionnaire correlated only
      in 85 per cent of the cases with the data provided by the time clock installed in
      the CPAP machine. The long-term compliance with nCPAP of the studied group was 92
      per cent. Four patients returned their masks within two months. It was possible
      to provide sufficient respiration to more than 90% of the patients using an
      average pressure between 7 and 8 cm water column. Respiration presented no
      problems for all six patients who had previously been treated with
      uvulopalatopharyngoplasty in our hospital. Despite the mask 41 patients slept
      with their partner in a common room.

PMID- 7818744
TI  - [Congenital choanal atresia and surgical correction].
AB  - 43 cases with congenital choanal atresia were observed in over 20 years. The
      indications for surgery of congenital choanal atresia and the different surgical
      approaches are discussed in detail. The transnasal approach should be performed
      in emergency situations or as first-aid treatment; the transmaxillary approach
      cannot be recommended any longer. The transpalatinal approach with the head in
      inclined position under microsurgical conditions has proved to be the surgical
      procedure of choice in most situations. 40 patients were operated on during
      infancy or childhood and followed up subsequently. 5 children showed bilateral
      choanal atresia; the other patients had unilateral complete atresia. In 9
      patients a transnasal approach was performed, in 7 cases there was recurrence of
      complete stenosis; after transpalatinal re-operations, relapse occurred in one
      case only. One patient was operated on via the transmaxillary approach. In 30
      cases the transpalatinal approach was the method of operation; relapse was seen
      in 6 cases only and could be revised by transpalatinal approach, excepted for one
      case. Our own experience and the present results show that the transpalatinal
      approach is suitable for adults as well as newborn and infants. On account of the
      better view of the operating area and optimal conditions for reconstruction, the
      transpalatinal approach is safer and long-term results are good.

PMID- 7818745
TI  - [Etiologically uncertain nasal obstructions in newborn infants].
AB  - This is a report on two neonates suffering from a severe nasal obstruction with
      respiratory distress. The cause of dyspnoea was identified as an abnormal bony
      narrowing at the level of the apertura piriformis. The etiology of this anomaly
      remains obscure. Surgical treatment was mandatory and performed as a transnasal
      approach using the operating microscope and otosurgical instruments. A special
      stent was used (U-shaped custom-made Portex tube) for several weeks to prevent
      recurrent narrowing. The advantage of a transnasal approach compared to the
      sublabial route is described and discussed.

PMID- 7818746
TI  - [Pleomorphic adenoma of the maxillary sinus].
AB  - Pleomorphic adenoma is the most common benign tumour of the salivary glands,
      especially the parotid gland. In the present paper we introduce the rare case of
      a pleomorphic adenoma of the maxillary sinus in a 82-year-old man who was
      referred to our outpatient clinic with nasal obstruction and occasional events of
      nose bleeding. Thorough investigation, using endoscopy and computed tomography,
      revealed a mass extending from the left maxillary sinus to the nasal cavity; the
      tumour was removed surgically; pathological examination showed a pleomorphic
      adenoma with no signs of malignancy.

PMID- 7818747
TI  - [A personal rhinoplasty concept for patients with cleft lip, jaw, palate].
AB  - In the treatment of patients with cheilognathouranoschisis, rhinoplasty is a
      great challenge, since the cleft lip and palate will also produce nasal
      deformation requiring surgical correction. Unilateral cleft lip and palate is
      usually associated with a pronounced septal deformity resulting in "crooked nose"
      as well as typical asymmetry of the apex of the nose and of the nasal vestibule.
      The anterior part of the septum is dislocated in the direction of the unaffected
      side and the lower border of the septum is at the same time subluxated to the
      opposite side. The dorsal part of the septum presents with a convex deformity
      towards the cleft side extending in horizontal and vertical direction. Severe
      septal deformities cannot usually be adequately corrected on the spot, i.e. loco,
      but since septal correction is of paramount importance for the appearance and
      functioning of the nose we performed an extracorporeal correction of the septum
      in 191 cleft patients during the period from January 1980 through May 1993.
      Another characteristic feature of the cleft nose is the oblique modiolus, or
      columella cochleae, which is shortened on the cleft side, and the S-shaped
      deformity of the lateral alar cartilage, which presents with a cranial
      dislocation in the dome, caudal deviation in the lateral part, and an overhanging
      ala. After correction of the entire cartilaginous nasal framework the surgeon is
      usually confronted with asymmetry of the soft tissue. Satisfactory correction can
      be achieved by means of a three-flap technique in the region of the modiolus,
      nasal ala and vestibular skin: A modiolus-based transpositional flap results in a
      symmetrical height of the modiolus.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7818748
TI  - [Velopharyngeal closure in adolescents after repair of cleft lip, jaw, palate or
      isolated cleft palate].
AB  - We examined two groups of teenagers (between 13 and 21 years of age) who had been
      surgically treated as small children for congenital cheilognathouranoschisis or
      cleft palate. A group of 62 teenagers had been treated by the Dept. of
      Orthodontics at the University of Erlangen-Nuremberg, the other group of 61 by
      the Dept. of Orthodontics at the University of Rostock. There were differences
      between the two departments in sequence and time of the surgical closure as well
      as in the frequence of velopharyngoplasties. The velopharyngeal closure was
      examined in all patients by means of a flexible fibre endoscope which was pushed
      forward endonasally up to the choanae. Simultaneously we judged the audibility of
      the nasal perflation while pronouncing /k/. A residual gap during articulation of
      /k/ with clearly audible or alternately clearly and discreetly audible nasal
      perflation was noted in 8 subjects in Erlangen and 14 subjects in Rostock. In
      subjects whose velum moved only anterior-posteriorly, closure was likely to be
      less good than in those with a circular closing mechanism of velum and lateral
      and/or posterior parts of the pharyngeal musculature. In rare cases we found a
      good velopharyngeal closure in spite of a large gap between the velum and the
      posterior pharyngeal wall at rest. This was the case when the velum moved more
      against the upper than the posterior wall of the nasopharynx. Velopharynxplasty
      did not reduce nasal airflow in case of insufficient function of the velar
      muscles. Differences in the mode of velopharyngeal closure might be due to
      statistically significant regional differences in skull structure.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7818749
TI  - [Digital subtraction dacryocystography (DS-DCG) and evaluation of results of
      endonasal lacrimal duct surgery].
AB  - 103 patients with obstructive epiphora, or illacrimation, underwent endonasal
      lacrimal surgery (dacryocystorhinostomy in the modification of Veis-Cdlaus and
      canaliculorhinostomy). Postoperative complications included local infections and
      were seen in 7 cases (6.8%). After finishing the treatment 90 patients (87.4%,
      Table 4) were free of symptoms and remained so for years of follow-up. Recurrent
      stenosis developed in 13 cases (12.6%). DS-DCG provides valuable information for
      confirming the indication for surgery and determining the surgical procedure in
      obstructive epiphora. In addition it may help to assess a successful outcome of
      the operation in the course of treatment (Fig. 7 and 8). By means of real time
      substraction the successive opacification is visualised on the monitor screen
      during injection thus controlling the examination. Incomplete contrast filling
      and overopacification are avoided. Digitalisation may direct the extent of
      homogenisation of the background of the radiographic image. Anatomical structures
      are preserved and weakly contrasted structures are depicted precisely and
      independent of the background. Stenoses before (Fig. 2 and 3), within (Fig. 4)
      and behind (Fig. 6) the lacrimal sac can be differentiated from complete,
      incomplete (Fig. 4) and functional stenoses.

PMID- 7818750
TI  - Applicability of standard irregular field calculations for high-energy photon
      beams.
AB  - Irregular-field calculations are usually based on a sector-summation technique.
      This technique typically involves separating the dose into primary and scatter
      components. While the conceptual basis for this procedure is valid at lower
      energies, it becomes suspect at higher energies. However, despite this
      limitation, a straightforward application of the technique yields good accuracy
      for 18 MV X-rays if certain limitations are observed. This work describes the
      calculational formalism used and the approximations made. Computed results are
      compared with measurements. The levels of uncertainty in both are discussed.

PMID- 7818751
TI  - A practical alternative to conventional five-field irradiation postmastectomy for
      locally advanced breast cancer.
AB  - A combination of electron and photon beams has been used as an alternative for
      the conventional five-field method to irradiate patients postmastectomy for
      locally advanced breast cancer. Anterior and posterior opposed photon beams treat
      in continuity the lateral chest wall, axilla, and supraclavicular lymph nodes. An
      adjacent anterior electron beam is used at an energy matched to the depth of the
      internal mammary nodes. It includes the anterior chest wall, but bolus is used in
      the lateral aspect to spare underlying lung. This electron beam eliminates the
      diverging junction between the internal mammary and medial tangential fields used
      in the conventional five-field technique. Overlaps along the junction between the
      photon and electron beams are minimized by placing the center of the photon field
      along its medial border. Measurements with an Alderson-Rando phantom show dose
      distribution advantages for this technique over the conventional five-field
      approach. There is less chance of underdosing tumor cells or of overdosing normal
      tissue along beam junctions. Clinical studies on 29 patients treated by this
      technique between July 1985 and December 1989 show increased rates of acute skin
      reactions, but otherwise similar side effects compared with 57 breast cancer
      patients treated with the five-field technique over the same time period. Local
      recurrence rates and patient survival rates were similar for the two groups.
      Given the dose-distribution advantages of this technique and its simple
      adaptation to accommodate unusual surgical scars or cancer recurrences, its use
      should be considered for postmastectomy patients with locally advanced breast
      cancer in well-equipped cancer treatment centers.

PMID- 7818752
TI  - Beam-hardening effects of wedges on a spoiled 6 MV beam.
AB  - The beam-hardening effects of the wedges on a 6-MV spoiled beam has been studied.
      The beam quality of all the wedged beams was found to be the same as the open
      beam. The dmax also stayed unchanged for all the wedges at all field sizes. The
      relative wedge factors were found to reflect the beam-hardening effect, which is
      a function of the wedge angles, depths, and field sizes. For the 15 degrees and
      30 degrees wedges, the relative wedge factor at depths less than 15 cm were found
      to deviate less than +2% for all fields, while those for the 45 degrees and 60
      degrees wedges for the same depth range from +3% to +4%. The surface doses were
      found to decrease with the wedged fields. For 15 degrees, 30 degrees, and 45
      degrees wedges, the decreases were found to be from 0 to -2.0%. For 60 degrees
      wedges, the largest deviation was found to be -2.5% for a field size of 10 cm x
      10 cm at a depth of 2 mm. The wedge factors at dmax were found to depend slightly
      on the field sizes. The use of an averaged wedge factor for each individual wedge
      was found to produce less than +/- 1.2% of error for all field sizes.

PMID- 7818753
TI  - Dose to breast in breast undergoing mantle treatments.
AB  - There is considerable interest in dose to the breast in patients undergoing
      mantle treatment for Hodgkin's disease. This is because the patients are quite
      young (adolescents) and the latency period between irradiation and appearance of
      tumors is long. In a prospective study TLD chips were placed in several positions
      on the breast of the patients undergoing mantle treatment. Some parts of the
      breast were in the irradiated region. TLDs were placed under 2 and 3 cm of
      superflab bolus. Mantle field is irradiated with 10MV X-rays with a 2 cm spoiler
      placed 15 cm from the patient's skin. Treatment is given at 120 cm SAD. Doses in
      the range of 20-30 cGy per fraction were measured underneath the blocks in most
      cases, and doses of 30-50 cGy were measured at the edge of the block. The
      prescription is 200 cGy per fraction. The implication of these results will be
      discussed.

PMID- 7818754
TI  - Comparison of Nucletron and ROCS brachytherapy treatment planning systems for LDR
      and HDR applications.
AB  - The Nucletron Plato system is being used in our Institute for both high dose rate
      (HDR) and low dose rate (LDR) treatment planning, while the radiation oncology
      computer system (ROCS) is used for external beam planning. This paper compares
      both systems, using a gynecological application for the LDR case and an
      esophageal application for the HDR. It is shown that ROCS may be used as a backup
      to the Nucletron treatment planning system for LDR and simple HDR cases. The
      Nucletron planning system is a better system than ROCS for both LDR and HDR
      applications.

PMID- 7818755
TI  - Quality assurance and dosimetric evaluation for an endocavitary unit.
AB  - The use of endocavitary contact therapy for selected rectal carcinomas continues
      to be an effective treatment option. Very small volumes are treated with an
      extremely high dose rate associated with rapid fall-off in depth and an overall
      high dose. The clinical benefits of the high dose rate leads to dosimetric and
      quality-assurance challenges. In addition, the operating room environment creates
      concerns in terms of dosimetry and radiation safety due to varying room line
      voltages and uncontrolled environments. The unit at our facility delivers 50 kVp
      X-rays using an SSD of 35 mm with lead-lined procotscopes of 24 and 29 mm. The
      dose rate is approximately 10 Gy per minute. Establishment of daily, monthly, and
      annual quality assurance reviews have been made and assessed. Parallel-plate
      ionization chambers measure outputs and relative depth dose with different
      phantoms. Silver bromide film is used to evaluate beam profiles. An electron
      diode system was chosen for day-of-treatment output checks. An ion chamber survey
      meter measures scatter and leakage exposure rates. Day-of-treatment output checks
      have assured output stability in various operating rooms. Trends in output have
      been confirmed by monthly ion chamber checks. Percent depth dose measurements
      carried out in liquid water compared well with accepted published data as did
      corrected polystyrene measurements. Radiation survey measurements detected
      acceptable exposure rate levels. The established comprehensive quality assurance
      program incorporates cross checking with multiple dosimetry systems. The
      confidence level of dose delivery has increased with the introduction of a day-of
      treatment output checks.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7818756
TI  - Bilateral arcs using "averaged beam's eye views": a simplified technique for
      delivering 3-D based conformal radiotherapy.
AB  - The purpose of this study is to describe a conformal radiotherapy technique for
      treating only the prostate with bilateral 120 degrees arcs using "averaged beams
      eye-views" (A-BEV). For this study a CT scan from a patient with a large prostate
      but with a low risk for seminal vesicle involvement was chosen for comparing
      several different treatment techniques. Dose volume histograms (DVHs) of the
      prostate, femoral heads, bladder, and rectum were compared for plans using
      "standard" bilateral 120 degree unblocked arcs (8 x 8 and 9 x 9 cm), similar
      sized arcs with "generic" (small corner) blocks applied, arcs using hand drawn
      "semi-conformal" blocks added, and arcs using the A-BEV. The A-BEV was generated
      by averaging the shapes of fixed lateral and oblique BEVs from a six-field plan.
      These arc techniques were compared to four-field conformal (4-FC) and six-field
      conformal (6-FC) techniques. The addition of generic corner blocks to a 9 x 9
      field resulted in a more favorable dose distribution than using open unblocked 9
      x 9 arcs. The technique employing the A-BEV resulted in an improvement in the
      DVHs compared to other arc techniques and to 4-FC techniques. The dose volume
      histograms associated with using this technique approached those associated with
      using a 6-FC technique. Treating only the prostate with blocked arcs generated
      using an A-BEV results in an improved dose distribution compared to unblocked
      arcs and 4-FC techniques. This blocked arc technique also results in a DVH that
      is comparable to using a more complex 6-FC technique. Blocks that are drawn on
      manually reduce the dose to the surrounding normal tissues but are associated
      with a greater risk of underdosing the target volume. This problem is diminished
      when computer generated conformal blocks are used.

PMID- 7818757
TI  - A single isocenter three-field breast irradiation technique using an empiric
      simulation and asymmetric collimator.
AB  - The treatment of abutting fields presents multiple difficulties, including
      problems of field overlaps or gaps, complexity of simulation, and the
      difficulties of daily setup and variation. Multiple techniques have been
      described for the treatment of the breast/chest wall and supraclavicular nodes
      using tangents and a matched supraclavicular field. The techniques described have
      used collimator angles, couch angles, and/or corner blocks in an attempt to match
      these fields with no overlap or gap. Some of these techniques required complex
      calculations or treatment devices to achieve a geometric match between fields. We
      describe a technique for treatment of breast and supraclavicular nodes that uses
      a single isocenter and requires asymmetric collimator jaws to give half-blocked
      fields. The simulation and setup are done empirically, with no complex
      calculations required. The daily setup and treatment can be done rapidly and
      reliably, with no extra equipment required. Custom blocks may be used to conform
      to the chest wall contour and decrease the amount of lung in the treatment
      fields.

PMID- 7818758
TI  - Use of styrene monomer-modified polyester in the fabrication of tissue-equivalent
      phantoms.
AB  - Tissue equivalent materials are often required both for routine quality control
      and for specialized studies in radiological physics. This work describes
      techniques and materials for casting of dosimetry devices from a widely available
      commercial resin suitable for use in a radiotherapy clinic. Methods are described
      for mixing and curing the material in such a way as to ensure complete reaction
      of the resin while maintaining a safe exothermic temperature. The clear plastic
      form of the cured resin is particularly useful for aligning measurement devices
      in the radiation field. Its specific gravity and narrow beam attenuation
      characteristics are similar to those of acrylic. The dosimetric characteristics
      of the material are reported, and its use in the construction of a patient
      phantom is described.

PMID- 7818759
TI  - Evaluation and quality control of a commercial 3-D dose compensator system.
AB  - A commercially available software/hardware system for automated design and
      fabrication of three-dimensional dose compensator molds has been tested for
      accuracy and precision as well as for its ability to provide adequate dose
      compensation at depth. To date, we have used this system to treat more than 50
      patients with either head and neck or lung malignancies. In 19 head and neck
      patients (38 compensators) the use of a customized compensator resulted in an
      average reduction of dose variance in the target volume from 13.8% (range of 7%
      21%) with uncompensated parallel-opposed fields to 4.5% (2%-7%) with custom
      compensated parallel-opposed fields. A similar reduction was seen in the dose
      variation across lung tumor volumes. The custom compensators were also tested for
      accuracy of fabrication and positioning; both were found to be accurate within +/
      1 mm of the design specifications for all compensators tested. Last, the
      dosimetric properties of the compensators were studied. The ratios of measured
      open-beam dose profiles to measured compensated-beam dose profiles were compared
      with the ratio of similar profiles calculated with a treatment planning system.
      These ratios were equal within +/- 2.9%, thus providing evidence of the fidelity
      of the compensator to its design and the accuracy of the treatment planning
      algorithm that designs 34 each compensator.

PMID- 7818760
TI  - A p53 mutation in exon 5 associated with adenovirus transformation.
AB  - The adenovirus type 5 (Ad5) 55-kDa E1B oncoprotein has been shown to form
      complexes with the p53 tumor suppressor protein. These complexes are thought to
      interfere with normal p53 activity and may be responsible for the paucity of p53
      mutations in cells transformed by these viruses. This report describes an example
      of a p53 mutation in exon 5 in an Ad5-transformed cell line that exhibited less
      expression of E1B 55-kDa protein and a longer tumor-latency phenotype than
      another Ad5-transformed cell line expressing wild-type p53. The finding of a p53
      mutation in an Ad5-transformed cell line is unusual, especially considering the
      current theory that p53-E1B interactions play an important role in adenovirus
      transformation. This mutation could represent an alternative method of
      inactivating p53 function in the absence of sufficient levels of E1B 55-kDa
      oncoprotein.

PMID- 7818761
TI  - Expression of epidermal ornithine decarboxylase and nuclear proto-oncogenes in
      phorbol ester tumor promotion-sensitive and -resistant mice.
AB  - This study was undertaken to assess the effects of a single or two sequential
      topical applications of 12-O-tetradecanoylphorbol-13-acetate (TPA) on the
      expression of c-fos, c-jun, junB, c-myc, and ornithine decarboxylase (ODC) in
      promotion-sensitive SSIN mice and the relatively promotion-resistant C57BL/6
      strain. Northern blot analysis demonstrated that a single promoting dose of TPA
      induced ODC mRNA expression 10- to 15-fold in both strains. Treatment of each
      strain with a second dose of TPA, 48 h (in C57BL/6 mice) or 72 h (in SSIN mice)
      after the first, led to hyperinduction of ODC activity. Although this involved
      transcription of new ODC mRNA, the hyperinduction of ODC enzyme activity was
      primarily posttranscriptional. Induction of c-fos mRNA or protein was maximal
      about 3 h after a single treatment in either strain but was sustained for at
      least 6 h in C57BL/6 mice. In contrast, two treatments of SSIN mice with TPA
      caused a rapid, strong c-fos induction 1-2 h after treatment, whereas C57BL/6
      mice responded no more strongly than after a single treatment. c-jun mRNA and
      protein were induced only slightly in either strain, but junB was induced about
      fivefold in SSIN mice and tenfold in C57BL/6 mice. Although c-myc was induced to
      comparable levels in both strains, the response was more prolonged in C57BL/6
      mice. Compared with SSIN mice, C57BL/6 mice responded to TPA treatment, in
      general, with changes in proto-oncogene mRNA to a higher level or for longer or
      both. Thus, although small differences in the expression of these genes were
      observed, they were not positively correlated with the differential sensitivity
      of SSIN and C57BL/6 mice toward tumor promotion by phorbol esters, with the
      possible exception of c-fos.

PMID- 7818762
TI  - Mutation, loss of heterozygosity, and recombination of the p53 gene in mouse
      forestomach tumors induced by 2-amino-3,4-dimethylimidazo[4,5-f]quinoline.
AB  - 2-Amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), a food mutagen, induces
      forestomach tumors in CDF1 mice. We established a polymerase chain reaction (PCR)
      single-strand conformation polymorphism (SSCP) analysis system to detect
      mutations in the mouse p53 gene exons 2-10, which encompass all five regions
      conserved among species, and a system to examine loss of heterozygosity (LOH)
      that uses newly identified polymorphisms between BALB/c and DBA mice, the
      parental strains of CDF1 mice. Four original forestomach tumors (one papilloma,
      two carcinomas, and one lymph-node metastasis) and four cell lines derived from
      four independent forestomach tumors were examined with the PCR-SSCP system and by
      polymorphism analysis. Of the four original tumors, the papilloma had a G-->A
      transition at the second position of codon 171, and one carcinoma had a G-->T
      transversion at the second position of codon 113 with loss of the wild-type
      allele, whereas the other two carcinomas had no detectable mutations. Of the four
      cell lines, two had a base substitution and LOH, and the other two had double
      mutations (a base substitution and a deletion). By amplification of the double
      mutations in a fragment, the two cell lines were shown to have four kinds of
      alleles, indicating induction of recombination within the p53 gene. Our results
      show that our PCR-SSCP analysis system is efficient for detecting p53 mutations
      in mouse genomic DNA and that alteration of the p53 gene plays a significant role
      in MeIQ-induced mouse forestomach carcinogenesis.

PMID- 7818763
TI  - Differential expression of prostaglandin H synthase isozymes during multistage
      carcinogenesis in mouse epidermis.
AB  - An anti-tumor-promoting effect of indomethacin and related nonsteroidal anti
      inflammatory drugs (NSAIDs) as well as the ability of the tumor promoter 12-O
      tetradecanoylphorbol-13- acetate (TPA) to increase the level of prostaglandins in
      murine keratinocytes and mouse epidermis in vivo has been repeatedly documented.
      Here, the expression of prostaglandin H synthase (PGHS) isozymes, which are major
      targets of NSAIDs, was investigated in different stages of tumor development in
      mouse skin. Mouse epidermis in vivo constitutively expressed PGHS-1. PGHS-1
      steady-state levels remained unchanged upon induction of acute or chronic
      epidermal hyperplasia by TPA and in papillomas and carcinomas generated by the
      initiation-promotion procedure, with 7,12-dimethylbenz[a]anthracene as initiator
      and TPA as promoter. Thus, the elevated prostaglandin level in the acute
      hyperplastic epidermis was very likely due to PGHS-2 induction. Repeated
      applications of TPA resulted in stationary hyperplasia and downregulation of PGHS
      2 expression and prostaglandin levels, suggesting that the epidermis had adapted
      to the TPA stimulus. In papillomas and carcinomas, however, constitutive
      overexpression of PGHS-2 was found, with a large amount of prostaglandin E2 and
      prostaglandin F2 alpha. Keratinocyte cell lines corresponding to different stages
      of tumor development also constitutively over-expressed PGHS-2. Considered with
      inhibitor studies, these data suggest that PGHS-2 has a critical role in skin
      carcinogenesis. The anti-tumor-promoting effect of the PGHS inhibitor
      indomethacin is specifically reversed by prostaglandin F2 alpha, indicating that
      this prostaglandin type has a significant role in tumor development.

PMID- 7818764
TI  - Upregulation of gap junctional communication and connexin43 gene expression by
      carotenoids in human dermal fibroblasts but not in human keratinocytes.
AB  - Consumption of dietary carotenoids has been statistically associated with
      decreased risk of cancer at several anatomic sites. In a model murine system of
      carcinogenesis (the 10T1/2 assay), we have previously shown that carotenoids can
      inhibit chemically and physically induced neoplastic transformation. This action
      is strongly correlated with the ability of carotenoids to increase gap-junctional
      communication (GJC) by induction of connexin43 (Cx43) gene expression. Here we
      extend these studies to human foreskin-derived dermal fibroblasts and
      keratinocytes. In fibroblasts, beta-carotene and canthaxanthin at concentrations
      between 10(-5) and 3 x 10(-6) M were found to strongly enhance GJC in a dose- and
      time-dependent manner. This was accompanied by an increase in the number of
      immunofluorescent junctional plaques recognized by an anti-Cx43 antibody and by
      an increase in Cx43 protein level as determined by western blot analysis. No
      decrease in proliferation rates was detected by [H3]thymidine labeling. Human
      keratinocytes grown in monolayer culture did not respond to carotenoids in terms
      of GJC as measured by dye transfer, immunofluorescent analysis of Cx43
      distribution, or Cx43 levels as measured by western blotting. Both cell types
      accumulated high levels of carotenoids. Because canthaxanthin, which has no known
      provitamin A activity in mammals, is as active in fibroblasts as is beta
      carotene, the carotenoid with the highest provitamin A activity, the induction of
      GJC and Cx43 expression by carotenoids in human dermal fibroblasts seems
      unrelated to their provitamin A status. The lack of response of keratinocytes
      suggests differences in regulation of Cx43 expression or in carotenoid
      processing.

PMID- 7818765
TI  - Loss of heterozygosity at chromosome 1q loci in rat mammary tumors.
AB  - To better characterize abnormalities affecting rat chromosome 1 during mammary
      carcinogenesis, tumors were induced by nitrosomethylurea in F1 hybrid rats
      polymorphic at multiple chromosome 1 loci. By means of restriction fragment
      length polymorphism and microsatellite length polymorphism analyses, we observed
      loss of heterozygosity or allelic imbalance affecting various loci on the q arm
      of chromosome 1 in a high percentage of the 49 tumors analyzed. Fifty percent of
      the tumors showed loss or imbalance affecting the most distal (1q55) INS1 (rat
      insulin 1 gene) locus. The MT1PA (metallothionein-1 pseudogene a) locus was
      observed to be affected in 58% of tumors induced in BUF/NCr x ACI/Vsp rats. Most
      of the losses appeared to have occurred by mitotic recombination. No parental
      bias was observed on the affected chromosome 1. Tumors were also screened for
      mutations in codon 12 of the Ha-ras-1 gene, which is located on 1q. We observed
      an association between the presence of mutation and allelic imbalance. These
      studies confirm our previous cytogenetic observations of a high level of
      nonrandom instability affecting rat chromosome 1 during mammary carcinogenesis.
      The observed loss of heterozygosity may indicate the existence of a putative
      tumor suppressor gene within the distal half of the 1q arm. These abnormalities,
      however, could also be related to the early stages of Ha-ras amplification.

PMID- 7818766
TI  - Styrene production, use, and human exposure.
AB  - Styrene is an extremely important commodity chemical used extensively in the
      manufacture of numerous polymers and copolymers, including polystyrene,
      acrylonitrile-butadiene-styrene (ABS), styrene-acrylonitrile (SAN), styrene
      butadiene latex, and styrene-butadiene rubber. Styrene is a component of
      cigarette smoke and automobile exhaust, and it may occur naturally at low levels
      in various types of foods. The highest potential human exposures to styrene occur
      in occupational settings, particularly those involving the production of large
      glass-reinforced polyester products such as boats, which require manual lay-up
      and spray-up operations. Substantially lower occupational exposures occur in
      styrene monomer and polymer production facilities. The general public is exposed
      to very low concentrations of styrene in ambient air, indoor air, food, and
      drinking water.

PMID- 7818767
TI  - Epidemiological studies of styrene-exposed populations.
AB  - The potential human carcinogenicity of styrene has been investigated mainly by
      epidemiological studies of occupationally exposed populations. Several cohort
      studies have suggested that workers exposed to styrene in the chemical industry
      have increased mortality from lymphatic and hematopoietic cancer. However, this
      finding has not been consistent and has not been reproduced in studies of
      reinforced plastics manufacturers, whose exposures to styrene are generally
      higher. The explanation for the observed associations may therefore be
      confounding by concomitant exposures to other chemicals such as benzene and
      butadiene, which are not used in the reinforced plastics industry. Despite their
      large size, the published studies of mortality and cancer incidence lack the
      statistical power to rule out an important hazard from long-term exposure to high
      (> 50 ppm) airborne concentrations of styrene. However, they indicate that any
      risk of cancer from lower levels of exposure is likely to be small.

PMID- 7818768
TI  - Review of the metabolic fate of styrene.
AB  - Styrene and styrene oxide have been implicated as reproductive toxicants,
      neurotoxicants, or carcinogens in vivo or in vitro. The use of these chemicals in
      the manufacture of plastics and polymers and in the boat-building industry has
      raised concerns related to the risk associated with human exposure. This review
      describes the literature to date on the metabolic fate of styrene and styrene
      oxide in laboratory animals and in humans. Many studies have been conducted to
      assess the metabolic fate of styrene in rats, and investigations on the
      metabolism of styrene in humans have been of considerable interest. Limited
      research has been done to assess metabolism in the mouse. The metabolism of
      styrene to styrene oxide and further conversion to styrene glycol (via epoxide
      hydrolase), mandelic acid, and phenylglyoxylic acid has been given considerable
      attention, and is considered to be the major pathway of activation and
      detoxication for humans. While the hydrolysis of styrene oxide to styrene glycol
      historically has been the favored pathway for the rat, studies in more recent
      years have indicated that glutathione conjugation also is a viable and
      significant pathway for both the rat and the mouse. This pathway has not been
      established in humans. Mandelic acid and phenylglyoxylic acid have been used as
      urinary markers of exposure in humans exposed to styrene. Extensive
      investigations have been conducted on the kinetics of styrene and styrene oxide
      in rodents. In people, the kinetics of styrene and styrene oxide in the blood of
      occupationally exposed workers and volunteers have been determined.
      Pharmacokinetic models developed in the last decade have become increasingly
      complex, with the most recent physiologically based model describing the kinetics
      of styrene and styrene oxide. This model shows pronounced species differences in
      sensitivity coefficients for styrene or styrene oxide between mice, rats, and
      humans, where mice are the more sensitive species to the Vmax for both epoxide
      hydrolase and monooxygenase. This result is particularly interesting in light of
      the recent findings of extensive mortality and hepatotoxicity for mice exposed to
      relatively low levels of styrene (250 to 500 ppm), while rats and humans exhibit
      only nasal and eye irritations at exposure concentrations well above 500 ppm.

PMID- 7818769
TI  - Styrene: toxicity studies--what do they show?
AB  - Styrene is efficiently metabolized to styrene oxide, which is itself readily
      detoxified by the same enzymes as those involved in the metabolism of various
      foodstuffs. Styrene oxide, like many intermediate metabolites of foodstuffs, is
      genotoxic and, if introduced directly into the stomachs of rodents in high
      doses/concentrations, gives rise to cancers of the forestomach. Exposing mice to
      doses of styrene high enough to overwhelm the capacity of the body to detoxify
      styrene oxide has been reported to increase lung tumor incidence in mice. The
      findings in eight epidemiological studies provide reassurance that occupational
      exposure to styrene is not associated with increased cancer risk. Tests for
      reproductive toxicity have given negative results, but effects on blood dopamine
      and hypothalamic and pituitary function and menstrual cycling under conditions of
      very high exposure have been reported. In light of all the available information,
      it is concluded that migration of styrene from food-wrapping materials is not a
      matter for toxicological concern.

PMID- 7818770
TI  - Evidence for DNA and protein binding by styrene and styrene oxide.
AB  - Styrene is metabolized to styrene oxide, a direct-acting mutagen and carcinogen.
      Styrene oxide reacts with DNA mainly at the N-7 position in guanine, but also at
      other sites and with other bases. Substitution occurs at both the alpha- and beta
      positions of the styrene molecule. Experiments with radiolabeled styrene and
      styrene oxide demonstrate that both have a low level of DNA binding activity in
      experimental animals. 32P-Postlabeling studies have demonstrated the potential of
      the technique to detect styrene-DNA adducts. Styrene oxide alkylates several
      nucleophilic sites in proteins, particularly cysteine sulfydryl, histidine
      imidazole, lysine amino, aspartic, and glutamic carboxylic groups, and the N
      terminal position. In experimental animals, styrene oxide treatment results in
      cysteine adducts in hemoglobin and albumin, valine adducts in hemoglobin, and
      carboxylic acid adducts in hemoglobin. The extent of alkylation is low compared
      with that produced by ethylene oxide. The available evidence indicates,
      therefore, that styrene and styrene oxide have low DNA and protein binding
      activities in vivo. There is preliminary evidence for the presence of DNA adducts
      and for adducts in hemoglobin and albumin in blood cells of styrene-exposed
      workers. Nevertheless, the applicability and sensitivity of DNA and protein
      adduct detection methods for monitoring human exposure to styrene remain to be
      determined.

PMID- 7818771
TI  - A critical review of the cytogenetic effects of styrene with an emphasis on human
      population monitoring: a synopsis.

PMID- 7818772
TI  - Review of styrene and styrene oxide long-term animal studies.
AB  - Eleven long-term toxicity studies were reviewed on styrene and five on styrene
      oxide in an effort to evaluate the potential carcinogenic activity of these
      chemicals in animals. The styrene studies included inhalation exposure (rats,
      mice, guinea pigs, and rabbits), intragastric gavage (rats and mice), drinking
      water (rats), and intraperitoneal injection (rats), while styrene oxide exposure
      was via intragastric gavage (rats and mice) or skin painting (mice). Each study
      was reviewed and evaluated for details and adequacy of design, adequacy of
      reported data, and interpretation. The results of this review are 1. There was no
      convincing evidence of carcinogenic activity of styrene in animals, although many
      of the studies were considered inadequate. 2. Styrene oxide was carcinogenic to
      the forestomach of both sexes of rats and mice after gavage exposure and was
      associated with an increase in liver neoplasms in male mice in one study. No
      carcinogenic activity was observed in mice after dermal exposure (skin paint). 3.
      None of the studies of styrene or styrene oxide reported here are well suited for
      extrapolating potential carcinogenic activity of either compound to humans
      because all have deficiencies in design, conduct, interpretation, or utilized a
      less than ideal route of exposure. A chronic state-of-the-art inhalation study is
      needed to evaluate this aspect of hazard assessment.

PMID- 7818773
TI  - The neuroepidemiology of styrene: a critical review of representative literature.
AB  - Because exposure to styrene occurs commonly in some industries and styrene is
      highly lipid soluble, it is reasonable to be concerned about the possibility that
      styrene is neurotoxic. Styrene, like many other solvents, volatile anesthetics,
      and drugs, does, at certain concentrations, produce acute changes in
      consciousness with consequent alterations of feelings, cognition, and psychomotor
      functioning. Such acute actions do not imply that styrene also would produce
      reversible or irreversible damage to the nervous system; the evaluation of long
      term exposures to styrene also is necessary to draw conclusions about the full
      range of neural effects that styrene might produce. To that end, several studies
      of workers exposed to styrene for up to 30 years have been undertaken in
      factories in many parts of the world. Epidemiologists have suggested that
      neuropsychological deficits such as slowing of reaction time, loss of color
      vision, and vestibulooculomotor dysfunction are reliably induced by styrene at
      levels near or below current exposure standards, which range from 20 to 50 ppm in
      most of the world. However, the workers so studied always were described as
      healthy, and the effects noted were considered to be subclinical. A detailed
      evaluation of much of the neuroepidemiological literature on styrene (38 papers
      and related literature), however, indicated that the findings were, almost
      universally, false positive outcomes due to (1) type I statistical error, (2) the
      action of some factor other than styrene, and (3) misinterpretation of data.
      Despite the study of workers exposed for many years, no indications of persisting
      damage to the nervous system were evident from this review. The conclusions of
      this review of the neuroepidemiology of styrene are consistent with those based
      on critical reviews of the solvent literature in general, with specific reference
      to the probable absence of such an entity as the "painter's syndrome" or "chronic
      toxic encephalopathy". Because the results on styrene neurotoxicity that provide
      an inclination to lower the current threshold limit values (TLVs) are false
      positive findings, there is no scientific basis for a reduction in the current
      TLV.

PMID- 7818774
TI  - Interpretation and clinical significance of alkaline phosphatase isoenzyme
      patterns.
AB  - Alkaline phosphatase (ALP, EC 3.1.3.1) is a membrane-bound metalloenzyme that
      consists of a group of true isoenzymes, all glycoproteins, encoded for by at
      least four different gene loci: tissue-nonspecific, intestinal, placental, and
      germ-cell ALP. Through posttranslational modifications of the tissue-nonspecific
      gene, for example, through differences in carbohydrate composition, bone and
      liver ALP are formed. Nowadays, most commercially available methods for
      separating or measuring ALP isoenzymes are easy to perform and sensitive and
      allow for reproducible and quantitative results. As more isoenzymes and isoforms
      have been characterized, confusion has arisen due to the many different names
      they were given. For the sake of simplicity and because of structural analogies,
      we propose an alternative nomenclature for the ALP isoenzymes and isoforms based
      on their structural characteristics: soluble, dimeric (Sol), anchor-bearing
      (Anch), and membrane-bound (Mem) liver, bone, intestinal, and placental ALP.
      Together with lipoprotein-bound liver ALP and immunoglobulin-bound ALP, these
      names largely fit the many forms of ALP one can encounter in human serum and
      tissues. The clinically relevant isoenzymes are sol-liver, Mem-liver, lipoprotein
      bound liver, and Sol-intestinal ALP in liver diseases, and Sol-bone and Anch-bone
      ALP in bone diseases. Many different isoenzyme patterns can be found in
      malignancies and renal diseases. This test provides the clinician with valuable
      information for diagnostic purposes as well as for follow-up of patients and
      monitoring of treatment. However, ALP isoenzyme determination will only provide
      clinically useful information if the patterns are correctly interpreted. In this
      respect, care should be taken to use the proper reference ranges, taking into
      account the age and sex of the patient. A normal total ALP activity does not rule
      out the presence of an abnormal isoenzyme pattern, particularly in children.
      Separating ALP into its isoenzymes adds considerable value to the mere assay of
      total ALP activity.

PMID- 7818775
TI  - Diagnosis, pathophysiology, and treatment of chronic twin-to-twin transfusion
      syndrome.
AB  - The discovery of a 'stuck twin' during an ultrasound examination has often been
      equated with twin-to-twin transfusion based to a great extent on postnatal
      confirmation of discordant fetal size and hemoglobin concentration. However, the
      diagnosis of twin-to-twin transfusion cannot be made with certainty after birth
      since virtually all monochorionic gestations have placental anastomoses and there
      are many causes of growth deficiency and abnormal hemoglobin concentration. The
      purpose of this study is to investigate the pathophysiology of chronic twin-to
      twin transfusion syndrome and apply the findings to the development of a
      management algorithm. In 42 twin gestations with stuck twin associated with acute
      hydramnios, we performed targeted ultrasound cordocentesis in each fetus and
      therapeutic amniocentesis. The diagnosis of chronic twin-to-twin transfusion
      syndrome required: sonographic evidence of monochorionicity; rapid reaccumulation
      of fluid after amniocentesis; discordant fetal size, and divergent fetal
      hematocrit measurements with at least one above or below the 95% confidence
      interval for gestational age. These criteria were met in 20 of 42 (48%)
      pregnancies. The mean gestation was 23.8 +/- 2 weeks (range 21-27 weeks). In 4
      pregnancies, the transfer of adult RBCs from the donor to the recipient was
      documented. Monochorionicity was confirmed in all postnatally. All recipients had
      polycythemia and hyperproteinemia. Hydrops developed only in the recipient twin
      (6 of 20) and was associated with an elevated umbilical venous pressure. All
      pregnancies were treated with aggressive serial therapeutic amniocenteses. There
      was no objective evidence that amniocentesis altered the magnitude of the
      shunt.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7818776
TI  - Nucleated erythrocytes in enriched and unenriched peripheral venous blood samples
      from pregnant and nonpregnant women.
AB  - The presence of nucleated erythrocytes was studied before and after enrichment
      with immunomagnetic beads and monoclonal antiglycophorin A (anti-GPA) antibody in
      the peripheral venous blood of 11 pregnant women at 10-16 weeks of gestation.
      Nucleated erythrocytes were identified by alkaline phosphatase antialkaline
      phosphatase immunostaining by means of anti-GPA antibody. In the unenriched cell
      samples, nucleated erythrocytes were found at frequencies of 1/2,800-1/83,000 in
      6 cases. The frequency of nucleated erythrocytes was increased up to 6 times by
      the enrichment.

PMID- 7818777
TI  - Poor pregnancy outcome and anticardiolipin antibodies.
AB  - The present study reports for the first time on the presence of anticardiolipin
      antibodies (aCL) in a population of 259 women with a history of recurrent
      abortion, intrauterine death, and/or neonatal death associated with fetal growth
      restriction, preeclampsia and abruptio placentae. The overall incidence of aCL in
      this study group was 20.5%, a statistically significant increase in comparison
      with a control group. The highest positive rate was observed among women who
      presented both recurrent abortion and intrauterine death (33.3%), the lowest was
      observed among women with a history of neonatal death. Our findings confirm that
      aCL are strongly linked with fetal loss. Thus, before planning a subsequent
      pregnancy, the presence of aCL should be tested in all women with poor pregnancy
      outcome.

PMID- 7818778
TI  - Stress mediators in the amniotic compartment in relation to the degree of fetal
      distress.
AB  - In an attempt to locate biochemical markers specific for fetal distress we
      measured the amniotic concentrations of beta-endorphin, ACTH, cortisol, dopamine,
      norepinephrine and epinephrine with its major metabolite metanephrine (MN) in
      pregnancies with documented fetal well-being and pregnancies complicated by
      hypertension and fetal distress. While higher levels of cortisol and MN were
      found only in a selected subgroup of highly compromised subjects (p < 0.001 and p
      < 0.005, respectively), beta-endorphin increased significantly under conditions
      of moderate or severe intrauterine sufferance (p < 0.001 in both cases). Due to
      higher levels of the opioid even during the initial stage of fetal discomfort we
      evaluated its characteristics as a possible clinical marker. Specificity was
      88.5%, whereas the sensitivity of 65.6% in the moderately compromised subgroup
      increased to 88.9% in severely suffering fetuses. Although more accurate and
      mainly real-time information on the fetal health status is obtained by means of
      biophysical methods, the determination of amniotic fluid beta-endorphin might be
      of clinical usefulness in prenatal diagnosis.

PMID- 7818779
TI  - Fetal abnormalities detected by sonography in low-risk pregnancies: discrepancies
      between pre- and post-termination findings.
AB  - In this geographically based study the findings on 158 abnormal fetuses,
      primarily diagnosed by routine antenatal ultrasound, are correlated with the
      results of the examinations subsequently carried out by a fetopathologist and a
      clinical geneticist. Ninety fetuses (57%) had a single malformation, 66 were
      polymalformed (42%) and 2 had no malformations. In 90% of all these cases, the
      prenatally and postnatally detected anomalies were identical; in 3% the defect
      established at necropsy was different from that diagnosed prenatally, and in 7%
      the predicted anomaly was absent. These values did not depend on whether single
      or multiple malformations were involved. In 57% of the polymalformed cases,
      however, the ultrasound examination missed at least one other diagnosable
      anomaly. On the basis of pathological and clinical genetic expertise, a risk of
      recurrence of the anomaly was revised in 13% of the single malformed cases and in
      53% of the multiple ones, i.e., in 30% of all the cases of malformation on
      average. This study confirms the need for the fetus to be examined by a
      pathologist and a clinical geneticist after termination of a not 'at risk'
      pregnancy in order to check the accuracy of the sonographic procedure, to confirm
      the reasons for terminating the pregnancy to the parents, and to be able to
      monitor the next pregnancy based on an accurate assessment of the risk of
      recurrence.

PMID- 7818780
TI  - Mathematical models for fetal growth: application for biparietal diameter
      measurement.
AB  - Evaluation of the adequacy of fetal growth by measurements of fetal size required
      theoretical formulae for the assessment of present size from previous
      measurements. The various models presented in the literature assume the same
      mathematical formula for the whole pregnancy. In this study, a model of different
      polynomial approximations for the early and late stages of the pregnancy is
      compared to two models which assume a single formula for both stages of the
      pregnancy. The standard error of estimate is lower for the sectioned model.

PMID- 7818781
TI  - Infrared fetoscopy in the sheep.
AB  - The strong light sources used in fetoscopy and embryoscopy may cause eye injuries
      to the fetus. To circumvent this potential hazard, we have successfully used an
      infrared light source and infrared video camera to perform 'night vision'
      fetoscopy in a fetal lamb model.

PMID- 7818782
TI  - Ultrasound-guided cardiac blood sampling of the rabbit fetus.
AB  - The object of the study was to determine whether cardiac sampling of the rabbit
      fetus could be successfully accomplished with minimal procedure-related loss.
      Pregnant rabbit dams were randomized to undergo ultrasound-guided fetal cardiac
      sampling in either the left or right uterine horn at 27 days of gestation;
      cesarean delivery was performed the following day. Liveborn pups from unsampled
      uterine horns underwent cardiac puncture immediately after birth. Fetal
      hematologic parameters were then compared to neonatal parameters. The acute fetal
      mortality from the sampled uterine horns was similar to that of the unsampled
      horns (3.6 vs. 4.5%). Fetal hematologic values were significantly higher than
      neonatal values with the exception of the reticulocyte count. This rabbit model
      offers a new approach for the evaluation of novel treatment modalities for
      hemolytic disease of the human fetus.

PMID- 7818783
TI  - Sickle cell and thiamine deficiency: case report of a fetal death.
AB  - The heterozygous state of the sickle cell trait is not known to be a cause of
      fetal death. This is a report of disseminated placental infarcts associated with
      thiamine deficiency in a patient with the sickle cell trait. This pathological
      association suggests an original physiopathological process.

PMID- 7818784
TI  - Assessment of the fetomaternal circulation in threatened abortion by transvaginal
      color Doppler.
AB  - Transvaginal color Doppler was used to investigate blood flow in the fetomaternal
      circulation of 60 women with threatened abortion and 90 women with normal
      intrauterine pregnancy. The obtained Doppler sonograms were analyzed and the
      resistance index (RI) was calculated in the maternal circulation, while in the
      fetal circulation the pulsatility index (PI) was used. There was no significant
      difference in the RI values of the maternal circulation between women with normal
      pregnancies and pregnancies complicated by bleeding, but with normal pregnancy
      outcome (p > 0.05). No differences in RI values of the uterine, arcuate and
      radial arteries were found between pregnancies with threatened abortion and
      normal pregnancy outcome and women with abnormal outcome (p > 0.05). In 9 of 21
      women with visible retrochorionic hematoma, the RI of the spiral arteries was
      higher on the hematoma side in comparison to the opposite side (p < 0.01). This
      could be a consequence of the mechanical compression caused by the hematoma. In 3
      of 4 cases of missed abortion, the RI of the spiral arteries was lower in
      comparison to the control group. Such findings could be caused by the
      vasodilatating products of inflammation which probably exist in such areas. There
      was no significant difference in terms of the PI of fetal blood vessels between
      normal pregnancy and threatened abortions with normal outcome, as well as between
      threatened abortions with normal outcome and subsequent abortions of live fetuses
      (p > 0.05).

PMID- 7818785
TI  - In utero nephrostomy catheter placement.
AB  - In utero diagnosis of severe oligohydramnios and fetal ureteral pelvic outlet
      obstruction resulted in the placement of nephrostomy catheters in two fetuses.
      The amniotic fluid index improved, mid-chest thoracic circumference increased and
      renal calyceal dilation decreased in both patients. Both neonates had evidence of
      pulmonary hypoplasia but survived. This new technique offers an alternative for
      antenatal management of obstructive uropathy when the bladder is not accessible
      or is distal to the site of the obstruction.

PMID- 7818786
TI  - Rapid exclusion of chromosomal aneuploidies by fluorescence in situ hybridization
      prior to fetal surgery for obstructive uropathy--a case report.
AB  - Ultrasound of a fetus at 17 weeks gestation revealed posterior urethral valve
      syndrome with anhydramnios. Fluorescence in situ hybridization (FISH) to detect
      aneuploidies of chromosomes 13, 18, 21, X and Y was performed on transitional
      cells from the fetal bladder obtained at percutaneous vesicocentesis, followed by
      conventional cytogenetics. Fetal urine was chosen due to unavailability of
      amniotic fluid for karyotypic analysis. A nonlethal (disomic) karyotype was
      suggested by FISH, and thus placement of a vesicoamniotic shunt was performed.
      The ability to prognosticate in cases of obstructive uropathy is not absolute,
      and fetal surgery for relief of urinary obstruction is best performed at the
      earliest possible gestational age. Thus, all available means for rapidly ruling
      out lethal congenital anomalies should be undertaken in cases of obstructive
      uropathy prior to any decision regarding fetal surgery.

PMID- 7818787
TI  - Inherited disorders of cobalamin metabolism.

PMID- 7818788
TI  - Hepatitis B and C viruses in the development of hepatocellular carcinoma.

PMID- 7818789
TI  - c-fos proto-oncogene regulation and function.

PMID- 7818790
TI  - The acute dose-dependent effects of ethanol on canine myocardial perfusion.
AB  - The acute effects of ethanol (1.0 g/kg and 1.5 g/kg, n = 4 and n = 5, yielding
      blood concentrations of 1.3 +/- 0.2 mg/ml and 2.4 +/- 0.3 mg/ml) on myocardial
      perfusion were studied in anesthetized, thoracotomized, artificially ventilated
      dogs by using a radioactive microsphere technique. The control group (n = 5)
      received saline. The smaller dose of ethanol decreased perfusion in the left
      ventricular myocardium from 0.737 +/- 0.122 to 0.555 +/- 0.122 ml/g/min (NS),
      whereas the greater dose nonsignificantly increased it, from 0.744 +/- 0.115 to
      0.819 +/- 0.119 ml/g/min (p < 0.01 between the groups). These changes were most
      evident in subendocardial layers (p < 0.01 both within the groups and between the
      groups). The greater dose of ethanol increased systemic vascular resistance (p <
      0.01 when compared to the control group). The changes in right ventricular
      myocardium were insignificant. The acute effect of ethanol on coronary blood flow
      is dose-dependent with small to moderate doses reducing demand for left
      ventricular flow but with increasing doses evoking not only an increase in demand
      for flow but also an increase in flow.

PMID- 7818791
TI  - Relative and combined effects of ethanol and protein deficiency on gonadal
      function and histology.
AB  - The aim of the present study is to analyse the relative and combined effects of
      ethanol and protein deficiency on serum testosterone and LH, and on gonadal
      histology, in ethanol fed rats. The study was performed in 32 animals divided
      into four groups, fed with the Lieber & DeCarli control, 36% ethanol, 2% protein,
      and 36% ethanol 2% protein containing diets, respectively. Two months later, rats
      were anaesthetized with pentobarbital and sacrificed, and the right testes and
      epididymus were carefully removed. Both ethanol and protein deficiency
      independently lead to a decrease in serum testosterone levels, and to testicular
      atrophy, lowest testosterone levels and highest degrees of atrophy being observed
      in the rats receiving the 36% ethanol, 2% protein containing diet. Both serum
      testosterone and testicular size and weight significantly correlated with final
      weight and serum albumin. Hypospermia, atrophy of the seminiferous tubules, and
      reduced epididymal diameter were also observed in this last group of animals.
      Thus, protein deficiency may contribute to hypogonadism of alcoholics.

PMID- 7818792
TI  - Chronic ethanol consumption prior to retrovirus infection alters cytokine
      production by thymocytes during murine AIDS.
AB  - Chronic ethanol (EtOH) consumption may be a cofactor in the development of
      acquired immune deficiency syndrome (AIDS). As the thymus is an unique site for T
      cell maturation, we investigated whether thymocytes from EtOH consuming mice were
      more predisposed to aberrant cytokine production due to retrovirus infection.
      Adult female C57BL/6 mice were fed 4.5% (v/v) in liquid diet or control liquid
      diet without EtOH for 10 weeks. All diets contained nutrients at only the
      recommended daily intake level for mice. Then all mice were infected LP-BM5
      retrovirus and were fed control liquid diets without EtOH. The body and thymus
      weights were not affected by EtOH consumption. However, thymocyte number and
      proliferation, which had been reduced during murine AIDS, were significantly
      further reduced by EtOH use. The production of IL-2 and IL-6 by thymocytes, which
      was lessened during retrovirus infection, were significantly further suppressed
      by dietary EtOH at 6 weeks postinfection, whereas levels of IL-4 and IFN-gamma by
      thymocytes, which were elevated during retrovirus infection, were significantly
      and slightly further increased by EtOH-treated mice prior to retrovirus
      infection, respectively. These data suggest that dietary EtOH consumption can
      modulate cytokine production by thymocytes, adversely affecting T cell
      differentiation, especially during retrovirus infection. These results provide
      additional evidence that EtOH consumption should be a cofactor during development
      of AIDS via producing altered cytokine production and then disrupting T cell
      differentiation.

PMID- 7818793
TI  - Acute inhibitory effect of alcohol on sodium-lithium countertransport.
AB  - To assess a possible acute effect of environmental factors on sodium-lithium
      countertransport (SLC), we determined the activity of this transport system in 14
      healthy volunteers, who are nonhabitual drinkers, before and 1 hour after intake
      of alcohol (0.8g/kg) with "Coke" as the vehicle. Alcohol significantly increased
      the "leak pathway" component of lithium efflux from a baseline value of 0.21 +/-
      0.02 to 0.24 +/- 0.02 mmol/Lcell.h(p < 0.003); and reduced the Vmax of the
      transporter (0.38 +/- 0.05 to 0.31 +/- 0.04mmol/Lcell.h;p < 0.0005) without
      significantly changing its affinity for external sodium. The reduction in Vmax
      was dependent on the initial activity of the transporter (r2 = 0.5). A plot of
      reduction in Vmax against the product of initial Vmax value and blood alcohol
      level in each subject revealed a stronger relationship (r2 = 0.86), suggesting
      that the observed change in Vmax was also dependent on blood alcohol level. Coke
      alone did not change any of the parameters. We conclude that alcohol acutely
      inhibits SLC as well as alters erythrocyte membrane in a manner that increases
      passive lithium efflux.

PMID- 7818794
TI  - Regulation of operant ethanol-reinforced behavior is genetically independent of
      regulation of withdrawal severity in WSP and WSR mice.
AB  - Selectively bred withdrawal seizure prone (WSP1 and WSP2) and withdrawal seizure
      resistant (WSR1 and WSR2) mice were used to test the extent to which severity of
      ethanol withdrawal response is predictive of the reinforcing effects of ethanol.
      Mice were systematically introduced to ethanol under a fixed ratio 1 (FR 1)
      schedule using adjunctive drinking methods. There were no significant differences
      in ethanol consumption between the lines during training. Subsequently,
      responding for ethanol concentrations of 8%, 0% (vehicle control), and 8% retest
      under a FR 1 schedule in the absence of food induction was measured. Group data
      showed that ethanol did not serve as a reinforcer in the test phase within any of
      the four lines, and there were no significant line differences in rate of
      responding, intake, or blood ethanol concentrations (BEC). Mice were next tested
      for responding for ethanol under a FR 4 schedule. Again, ethanol did not serve as
      a reinforcer for any of the four groups, and there were no significant
      differences between the lines. However, further analysis showed that there were
      individual differences in responding within each group, some animals were
      apparently reinforced by ethanol, while others showed no reinforcement and some
      appeared to avoid ethanol. There was no systematic pattern within or between
      groups for these individual differences in responding. Thus, both the group
      results as well as the behavior patterns of individual animals are consistent
      with the conclusion that genes regulating rewarding effects of ethanol appear to
      be segregating randomly across groups and are independent of genes mediating
      ethanol withdrawal severity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7818795
TI  - Phenotypic characterization of second generation offspring of alcohol-sensitive
      ANT and alcohol-insensitive AT rat lines.
AB  - The alcohol-sensitive ANT and the alcohol-insensitive AT rat lines developed by
      selective breeding for differential sensitivity to motor impairment on the
      tilting plane by a moderate ethanol dose (2 g/kg, IP), were cross-bred to produce
      second generation (F2) offspring to study phenotypic correlations between various
      behavioral and biochemical properties and the degree of initial alcohol
      sensitivity in the tilting plane test. The F2 population (n = 75) was subjected
      to alcohol sensitivity tests using a tilting plane test and a sleep time test,
      and to the elevated plus-maze test of sober activity and anxiety. Finally, the
      animals were sacrificed and the concentrations of dopamine and its acidic
      metabolites were analyzed in their striatal tissues. Serum corticosterone was
      determined to obtain information about the stress responses of the animals after
      the tilting plane test. The behaviors studied had no significant correlations
      with each other, suggesting that the various genetic and environmental factors
      affecting these behavioral phenotypes are different for each behavior. The
      biochemical measures yielded some correlations with the tilting plane test
      results that were contrary to the differences between the parent rat lines
      (dopaminergic indices) or that were confounded by the correlations with the body
      weight of the animals (corticosterone). Body-weight independent correlational
      tendency between the alcohol-induced impairment in motor performance and serum
      corticosterone concentration, however, fitted the differences between the parent
      lines, suggesting that stress mechanisms cannot be fully excluded as factors
      contributing to the differential alcohol sensitivity between the ANT and AT rat
      lines.

PMID- 7818796
TI  - Apoptosis and gene expression: perspectives on alcohol-induced brain damage.
AB  - Apoptosis, genetically preprogrammed death of scattered cells, leaves few
      histological traces and is compatible with autopsy findings in brains of
      alcoholics. This type of cell death could be triggered by chronic exposure to
      alcohol. Interactions between alcohol and the activating and inhibiting molecular
      events of the apoptotic cascade could occur at several different levels. Sites of
      alcohol action could range from the transcription of the apoptosis genes to
      translation and posttranslational modifications of their protein products. The
      recent developments of in situ hybridization technology make it possible to
      determine the levels of the neurotoxic actions of ethanol and to detect early
      stages of toxicity where increased mRNA activity may compensate for losses of
      receptors, enzymes, peptide transmitters, or structural proteins. The potential
      for treatment with antisense nucleotides is discussed.

PMID- 7818797
TI  - Serotonin 5-HT3 antagonists fail to affect ethanol self-administration of rats.
AB  - Five Long-Evans hooded rats were trained to lever press according to fixed-ratio
      5 reinforcement schedules for 0.06 ml dipper deliveries of 8% w/v ethanol during
      daily (M-F) 0.5-h experimental sessions. After ethanol self-administration was
      established, doses of the serotonin 5-HT3 antagonists, ondansetron (0.03-3.0
      mg/kg), granisetron (0.01-1.0 mg/kg), and SC-51296 (0.1-10.0 mg/kg) were
      administered prior to ethanol sessions to determine their effects on ethanol self
      administration. None of the doses of the antagonists had significant effects on
      numbers of obtained ethanol deliveries. Subsequently, each antagonist
      (ondansetron, 0.1 mg/kg; granisetron, 0.3 mg/kg; SC-51296, 0.1 mg/kg) was
      administered b.i.d. for five consecutive daily sessions. During none of these
      chronic tests with the 5-HT3 antagonists were there significant main effects of
      drug administration. Overall, these results do not support the hypothesis that
      the serotonin 5-HT3 antagonists would have robust therapeutic efficacy in the
      treatment of alcoholism.

PMID- 7818798
TI  - Serotonergic neurons in the alcohol preferring rats.
AB  - Previously, we have shown that the serotonin (5-HT) content and fiber density in
      a number of terminal brain regions have been found to be decreased in the
      selectively bred, alcohol preferring (P) rats than in the alcohol nonpreferring
      (NP) rats. In this study, we further report that, compared with NP rats, there
      were fewer 5-HT-immunostained (5-HT-IM) neurons in the major ascending raphe
      nuclei of the P rats. Among the three major groups of 5-HT neurons responsible
      for the majority of ascending projections to forebrain, dorsal raphe (B7), median
      raphe (B8), and B9, there were fewer 5-HT-IM neurons in the median and dorsal
      raphe (not including nucleus oralis) of P rats, compared with NP rats (unpaired
      Student's test). No difference was observed in the B9 group. When the animals
      were treated with pargyline and L-tryptophan to enhance the 5-HT in the neurons,
      the number of 5-HT-IM neurons increased in both lines of rats. However, the
      difference in the number of 5-HT neurons between the rat lines remained. The
      intensity of 5-HT-IM was also found to be lower in the dorsal raphe neurons of
      the untreated P than in the untreated NP rats. The decreased 5-HT-IM was
      supported by high performance liquid chromatography measurement of 5-HT content,
      which also indicated that 5-HT content of the dorsal raphe was lower in the P
      than in the NP rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7818799
TI  - Selective effects of ethanol exposure on metabotropic glutamate receptor and
      guanine nucleotide stimulated phospholipase C activity in primary cultures of
      astrocytes.
AB  - The effects of acute and chronic ethanol exposures on the stimulation of inositol
      specific phospholipase C by metabotropic glutamate receptor activation were
      determined in primary cultures of rat cortical astrocytes. Phospholipase C
      activity was monitored by the formation of [3H]inositol phosphates in the
      presence of lithium in cells prelabelled with [3H]inositol. Acute exposure to 200
      mM ethanol had no significant effect on either basal or L-glutamate stimulated
      [3H]inositol phosphate formation. In cells chronically exposed to ethanol for 4
      days, the [3H]inositol phosphate responses to L-glutamate, quisqualate, and the
      selective metabotropic receptor agonist, 1S,3R-1-amino-cyclopentane-1,3
      dicarboxylic acid (trans-ACPD), were significantly inhibited when compared to
      control (untreated) cells. In contrast, chronic ethanol exposure had no
      significant effect on the [3H]inositol phosphate response to endothelin-1, a
      peptide structurally and functionally unrelated to L-glutamate. Similarly, the
      stimulation of [3H]inositol phosphate formation by the stable GTP analog, guanine
      5'-(gamma-thiotrisphosphate), was also unaffected by chronic ethanol exposure.
      The results suggest that chronic ethanol exposure does not affect the coupling of
      GTP binding proteins to phospholipase C, but rather acts in a selective manner to
      either alter the metabotropic receptor number or to disrupt the normal coupling
      of this receptor to its GTP binding protein, which may in turn affect receptor
      affinity.

PMID- 7818800
TI  - Influence of the 5-HT1A receptor agonist ipsapirone on voluntary alcohol intake
      in rats.
AB  - The effect of the azapirone derivative ipsapirone on anxiety and the free-choice
      consumption of alcohol was studied in male rats. Animals were housed three in a
      cage with a different composition each day to increase anxiety. The animals were
      offered a two-bottle free choice consumption of tap water or a 5% ethanol
      solution. Ipsapirone was given in the drinking fluid daily at about 10 mg/kg per
      day. As expected, social unstable groups exhibited a higher level of anxiety as
      compared to social stable groups. Ipsapirone reduced significantly the anxiety in
      the unstable group. Pretreatment with ipsapirone before alcohol exposure resulted
      in a marked decrease of subsequent ethanol intake by about 45% as compared to
      drug free control animals. Administration of the drug to rats already drinking
      alcohol showed a similar decrease of ethanol intake by about 50%. These results
      indicate that the relatively specific 5-HT1A receptor agonist ipsapirone, given
      orally, reduces anxiety as well as alcohol initiation or maintenance in rats.

PMID- 7818801
TI  - Ethanol disordering of GM1-enriched short-sleep synaptosomal plasma membranes.
AB  - The Long-Sleep (LS) and Short-Sleep (SS) mouse synaptosomal plasma membranes
      differ in ethanol sensitivity at superficial membrane regions, which corresponds
      with the behavioral response of the mice to ethanol hypnosis. The only
      significant difference between these synaptosomal plasma membranes is the
      synaptosomal monosialoganglioside (GM1) content, LS > SS. Here, GM1 was examined
      as a parameter for increasing membrane sensitivity to ethanol effects in the
      ethanol-resistant SS membranes. Synaptosomal plasma membranes from SS mice were
      allowed to incorporate exogenous GM1. Membrane order was then studied at the
      surface, intermediate, and interior regions of the membranes by delayed Fourier
      transform proton NMR in the presence and absence of perdeuterated ethanol.
      Differences in membrane order were observed in all three membrane regions with
      increasing perdeuterated ethanol concentrations depending on the synaptosomal GM1
      content.

PMID- 7818802
TI  - Immobilized-metal-chelate regenerable carriers: (I). Adsorption and stability of
      penicillin G amidohydrolase from Escherichia coli.
AB  - Penicillin G amidohydrolase (PGA) was immobilized on Cu(II)-chelate regenerable
      sorbents. A long spacer was essential for binding, such as bisoxirane in the case
      of Sepharose 4B or glycidoxypropyltrimethoxysilane in the case of silica-based
      carriers. The stability of the PGA-carrier was determined both by the interaction
      forces between PGA and the metal-chelate sorbent and the presence of penicillin G
      (Pen G). The force of interaction between the enzyme and the metal-chelate
      sorbent was low, and Pen G competed for binding sites at high concentrations. The
      carrier with a small pore size demonstrated diffusion restrictions during
      immobilization of PGA, resulting in low activities of the immobilized enzyme.
      This carrier could not be completely regenerated. Carriers with an average pore
      size of 55 nm or larger displayed fewer diffusion restrictions. The corresponding
      Cu(II)-chelate sorbents were regenerated several times.

PMID- 7818803
TI  - Preparation and characterization of biotinylated red blood cells.
AB  - Biotinylation of intact mammalian red blood cells (RBC) was performed either by
      attachment to the amino groups by means of biotin N-hydrosuccinimide ester (NHS
      biotin) or by oxidation of the induced aldehyde groups of the RBC membrane by
      biotin hydrazide. Comparison of these different procedures showed that
      biotinylation by NHS-biotin provided the highest cell recovery (> 90%), the
      binding of approximately 1000 biotin molecules/cell (on mouse RBC) and the 24 h
      survival in circulation was unaffected. In contrast, biotin hydrazide produced
      cell recovery in the 5-30% range (depending on the extent of oxidation), an
      undetectable number of molecules of biotin/cell and negligible 24 h survival.
      Among the NHS derivatives of biotin, further studies were performed on those
      containing a spacer arm of 2.2 nm (22 A) [sulphosuccinimidyl-6-(biotinamido)
      hexanoate]. In vitro this derivative was similar to, or better than, the NHS
      biotin in terms of cell recovery and the number of molecules/cell. In vivo this
      derivative showed a 24 h circulation survival similar to that of NHS-biotin.
      Unfortunately, biotin bound with such a spacer arm is lost after a few days of
      RBC circulation, probably due to plasma biotinidase. Possible applications of
      biotinylated RBCs include the in vivo measurement of RBC volume, the RBC survival
      and the delivery of enzyme and antigens.

PMID- 7818804
TI  - Oligomycin-sensitivity of hexose-sugar catabolism in the bloodstream form of
      Trypanosoma brucei brucei.
AB  - The catabolism of hexose sugars and glycerol by the bloodstream form of
      Trypanosoma brucei brucei incubated with oligomycin was investigated. Oligomycin
      at a concentration of 10 micrograms/10(8) trypanosomes inhibited the catabolism
      of fructose, glucose and mannose by 70-80%, but not that of glycerol.
      Permeabilization of the trypanosome membranes by digitonin did not reverse the
      inhibition by oligomycin. Oligomycin did not inhibit pyruvate production in
      digitonin-permeabilized trypanosomes which were catabolizing exogenous glycolytic
      intermediates. It is concluded that the oligomycin-sensitive glycolysis is
      dependent on trypanosome membrane integrity. Oligomycin caused a rapid increase
      in the levels of hexose phosphates and some triose phosphates, but a decrease in
      the levels of glycerate 2-phosphate and phosphoenolpyruvate. There was a
      crossover point in the sequence of reactions between the formation of glycerol 3
      phosphate and glycerate 2-phosphate during catabolism of the hexoses. Addition of
      the same concentration of oligomycin caused no change in the levels of glycolytic
      intermediates during the catabolism of glycerol. It is proposed that the
      catabolism of hexose sugars requires the transport of glycerol 3-phosphate from
      the glycosome via a glycerol 3-phosphate carrier which is probably inhibited by a
      hexose-sugar derivative formed on inhibition of the mitochondrial Mg(2+)-ATPase
      by oligomycin.

PMID- 7818805
TI  - Industrial design of enzymic processes catalysed by very active immobilized
      derivatives: utilization of diffusional limitations (gradients of pH) as a
      profitable tool in enzyme engineering.
AB  - We have developed integrated studies of enzyme reaction engineering for the
      hydrolysis of penicillin G catalysed by very active penicillin G acylase (PGA)
      derivatives. We have studied the distinct effect of a key variable (pH) on
      different industrial parameters (e.g. activity/stability parameters). In this way
      we have demonstrated, in contrast with that proposed by other authors, that the
      generation of gradients of pH inside the porous structure of very active enzyme
      derivatives may be not a problem but a 'very profitable tool' to improve the
      whole set of industrial parameters. In this way we can establish two distinct
      'optimal pH values': (i) the one inside the particle of the biocatalyst and (ii)
      the one in the bulk solution. The use of an external pH of 8.0 associated with
      the promotion of a controlled decrease in internal pH (e.g. around a mean value
      of 5.5) was very useful to simultaneously obtain interesting values of all
      industrial parameters: (i) very high hydrolytic yields (higher than 97%); (ii) a
      very important increase on the stability of PGA derivatives (higher than a 50
      fold factor); and (iii) a very small decrease in operational activity
      (approximately 15%) as compared with the one of soluble enzyme at pH 8.0 with no
      diffusional hindrances.

PMID- 7818806
TI  - Indirect costs of HIV/AIDS mortality in Canada.
AB  - OBJECTIVE: To estimate and compare the societal impact of HIV infection and AIDS
      with other selected causes of male mortality in terms of the indirect costs of
      future production lost. DESIGN: Descriptive, population-based economic evaluation
      study. PATIENTS: All men aged 25-64 years for whom HIV/AIDS or another selected
      disease was listed as the underlying cause of death in Canada from 1987 to 1991,
      as reported to Statistics Canada. SETTING: Canada. MAIN OUTCOME MEASURES: Present
      value of future earnings lost for men using a human capital approach based on
      potential years of life lost in men aged 25-64 years. RESULTS: Assuming a 2%
      annual growth in earnings and a 3% annual real discount rate, the present value
      of the total loss of future production for all men aged 25-64 years who died in
      Canada during 1987-1991 was estimated to be 39.74 billion 1990 US$. Deaths due to
      HIV/AIDS accounted for 5.3% of this total loss or 2.11 billion in 1990 US$.
      Future production loss due to HIV/AIDS more than doubled during the period from
      1987 to 1991, from 0.27 to 0.60 billion 1990 US$. The loss in future earnings
      attributable to HIV/AIDS was exceeded only by that of ischaemic heart disease
      (15.2%), suicide (9.4%), motor vehicle accidents (6.6%), and lung cancer (6.6%).
      In total, these five causes of death accounted for 43.1% of the total indirect
      cost of production lost for men aged 25-64 years during the 5-year period.
      CONCLUSION: Our findings demonstrated HIV/AIDS mortality is already having a
      dramatic impact on future wealth production in Canada. If the past trend
      continues, the production lost in 1994 should exceed 0.86 billion 1990 US$ and
      will account for more than 10% of the total annual loss for men aged 25-64 years.

PMID- 7818807
TI  - Prevention indicators for evaluating the progress of national AIDS programmes.

PMID- 7818808
TI  - Prevention of HIV infection.

PMID- 7818809
TI  - T-cell proliferation to subinfectious SIV correlates with lack of infection after
      challenge of macaques.
AB  - OBJECTIVES: To analyze correlates of protection in macaques exposed to SIV.
      METHODS: Peripheral blood mononuclear cells (PBMC) from macaques inoculated
      intrarectally with various dilutions of SIV were examined for their in vitro
      proliferative response to SIV envelope peptides and generation of SIV-specific
      antibodies. Some macaques previously exposed intravenously to subinfectious doses
      of SIV were subsequently challenged 16 months later with an infectious
      intrarectal dose of SIV. RESULTS: The viral-specific immune responses of macaques
      exposed to infectious doses of SIV were characterized by generation of antibodies
      and weak or undetectable T-cell-mediated responses. In contrast, macaques
      inoculated with doses of SIV below the threshold required for seroconversion and
      recovery of virus exhibited T-cell proliferation in response to SIV envelope
      synthetic peptides. The macaques that had previously been exposed to SIV resisted
      the subsequent virus challenge, whereas the naive macaques (never exposed to SIV)
      all became infected. CONCLUSIONS: The inability to productively infect macaques
      previously exposed to subinfectious doses of SIV suggests that a T-cell-mediated
      response may confer long-term protection against infection, and that AIDS
      vaccines should be designed to optimize the cellular arm of the immune response.

PMID- 7818810
TI  - Staphylococcal superantigens activate HIV-1 replication in naturally infected
      monocytes.
AB  - OBJECTIVES: To study the effects of microbial superantigens, Staphylococcal
      exotoxins (SE), on HIV replication in monocytes following binding to and
      signalling through major histocompatibility complex (MHC) class II molecules.
      METHODS: We investigated the effects of SE on HIV replication and monokine
      production in three different in vitro models of monocyte culture: chronically
      infected monocytic cell line U1, acute infection of normal monocytes by different
      HIV-1 strains, and naturally-infected monocytes from seropositive patients. p24
      antigen, interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha production was
      measured by specific enzyme-linked immunosorbent assay (ELISA). RESULTS:
      Staphylococcal enterotoxin B and toxic shock syndrome toxin-1 (1-1000 ng/ml) are
      powerful inducers of HIV-1 expression in U1 cells pretreated with granulocyte
      macrophage colony stimulating factor. SE induce viral replication in short-term
      cultures (days 6-21) of monocytes infected in vitro by HIVBa-L, HIVLAI, or
      naturally infected in vivo. Induction of HIV expression requires direct
      interactions of SE with MHC class II molecules but not T-cell receptor binding
      and T-cell-monocyte contact. Anti-TNF-alpha and anti-IL-6 neutralizing monoclonal
      antibodies inhibit by over 61% SE-induced HIV replication. CONCLUSIONS: Using SE
      we have linked two important pathways for the regulation of HIV replication in
      monocytes, namely signalling through MHC class II molecules and monokine
      production potentially mediated by induction of the pleiotropic cellular
      transcription factor NF-kappa B. In HIV-infected patients bacterial infections
      are common and could be an important cofactor in the immunopathogenesis of AIDS
      by inducing HIV replication in latently infected monocytes. Their prevention
      might emerge as beneficial in these patients.

PMID- 7818811
TI  - Genotypic subtypes of HIV-1 in Cameroon.
AB  - OBJECTIVE: The only two HIV-1 strains (ANT70 and MVP5180) reported to date from
      Cameroon are members of the outlier clade (group O). In this study, we assessed
      the prevalence of group O viruses and other HIV-1 subtypes in Cameroon. DESIGN: A
      phylogenetic analysis of 18 HIV-1 strains isolated from seropositive individuals
      from Yaounde and Douala, Cameroon. METHODS: A 900 base-pair fragment of the env
      gene coding for V3, V4, V5, and the beginning of gp41 of 17 out of 18 HIV-1
      isolates from Cameroon was amplified, cloned and sequenced using polymerase chain
      reaction. A phylogenetic tree was constructed. RESULTS: The overall env
      nucleotide sequence divergence among the Cameroon isolates ranged from 6.1 to
      27.5%. In a phylogenetic tree, six subtypes were identified when compared with 23
      reference strains of different geographic origin. Of these 17 Cameroonian
      strains, 11 (61%) were of subtype A of which the interpatient distances at the
      sequence level varied from 6.1% to 18.3% (average, 11.9%). Three (17%) strains
      were of subtype F, and the other three strains (6% each) belonged to subtypes B,
      E and H, respectively. The remaining isolate was classified as belonging to group
      O, on the basis of the sequence of part of the pol gene. A very broad spectrum of
      different tetrameric amino-acid sequences was observed at the apex of the V3
      loop. Eleven strains contained the tetrameric globally predominant GPGQ sequence
      at the tip of the V3 motif. Two strains had the GPGR sequence typical of the
      American and European HIV-1 strains. The remaining tetrameric sequences included
      GPGS, GSGQ, GRGQ, and GLGR. CONCLUSION: These findings on a limited number of
      viruses suggest extensive env gene diversity of HIV-1 strains from Cameroon, and
      could have implications for vaccine development in Africa.

PMID- 7818812
TI  - Interleukin-12 enhances antigen-specific proliferation of peripheral blood
      mononuclear cells from HIV-positive and negative donors in response to
      Mycobacterium avium.
AB  - OBJECTIVE: To determine if the addition of recombinant (r) human interleukin (IL)
      12 enhances in vitro proliferative responses to Mycobacterium avium of peripheral
      blood mononuclear cells (PBMC) from HIV-positive donors with CD4 cell counts <
      100 x 10(6)/l. DESIGN AND METHODS: PBMC proliferative responses to virulent and
      avirulent serovars of M. avium in the presence and absence of exogenously added
      IL-12 were determined in 24 HIV-positive and 11 HIV-negative donors by 3H
      thymidine uptake assay. Changes in CD4 and CD8 cell populations after IL-12
      treatment and M. avium stimulation were analyzed by FACS. RESULTS: IL-12
      significantly enhanced proliferation of PBMC to both virulent and avirulent M.
      avium from all 24 HIV-positive donors (P = 0.0001) although the magnitude varied
      for each donor. In contrast, addition of IL-12 to PBMC from HIV-negative donors
      only increased the proliferative responses to the virulent M. avium serovar 4 (P
      = 0.0044). PBMC from HIV-positive donors in the presence of IL-12 responded
      better to the avirulent serovar of M. avium than the virulent serovar 4.
      Proliferative responses of HIV-positive donors to M. avium alone, however, were
      significantly less (P = 0.0013) than that of HIV-negative donors. Increased
      proliferative responses of HIV-positive donors were independent of CD4 counts. No
      significant changes in the ratio of CD4+ to CD8+ T cells occurred in either HIV
      positive or negative donors under any culture conditions. CONCLUSION: In vitro
      proliferative responses of PBMC from HIV-positive donors to M. avium were
      significantly enhanced by the addition of human rIL-12, which was not dependent
      on their CD4 cell counts. The use of IL-12 as an enhancer of cell-mediated
      immunity in AIDS patients against M. avium infections deserves further study.

PMID- 7818813
TI  - HIV-1 immunogen induction of HIV-1-specific delayed-type hypersensitivity:
      results of a double-blind, adjuvant-controlled, dose-ranging trial.
AB  - OBJECTIVE: To investigate the capacity of an HIV-1 immunogen to induce or augment
      HIV-1-specific delayed-type hypersensitivity (DTH) over a range of doses in
      asymptomatic HIV-1-seropositive adults. DESIGN: A single center, double-blind,
      adjuvant-controlled, dose-ranging trial involving 48 HIV-1-seropositive
      asymptomatic patients. Each dose group consisted of 12 subjects, eight receiving
      HIV-1 immunogen and four incomplete Freund's adjuvant (IFA). The doses studied
      were 50, 100, 200, or 400 micrograms (total protein). The HIV-1 immunogen was
      administered intramuscularly every 4 weeks for 36 weeks, with dosing contingent
      on the lack of an HIV-1 immunogen DTH response. A maximum of six doses was
      permitted. METHODS: Immunogenicity was assessed every 4 weeks by DTH skin testing
      to the inactivated HIV-1 antigen in saline with > 9 mm induration representing a
      response to immunization. Changes in p24-antibody levels were determined by
      endpoint titration using an enzyme-linked immunosorbent assay and Western blot.
      RESULTS: At doses of > or = 100 micrograms, all treated patients demonstrated
      significant differences in the ability to mount an HIV-1-specific cell-mediated
      response relative to adjuvant controls. Dose-related response patterns were
      observed in the period between doses and the occurrence of rises in HIV-1 DTH.
      Treatment appeared to increase p24-antibody titers as well as reactivities to
      other HIV-1 antigens as determined by Western blots. The HIV-1 immunogen was well
      tolerated. CONCLUSIONS: The minimum dose of the HIV-1 immunogen in IFA required
      to induce HIV-1 DTH relative to the IFA control group was 100 micrograms in this
      patient population.

PMID- 7818814
TI  - Community-acquired Pseudomonas aeruginosa pneumonia in patients with HIV
      infection.
AB  - OBJECTIVE: To describe the clinical and radiographic presentation, risk factors,
      response to therapy and outcome of 16 patients with HIV infection and pulmonary
      infections caused by Pseudomonas aeruginosa. DESIGN: Retrospective review of
      medical records. SETTING: An academic tertiary-care hospital. PATIENTS: Sixteen
      patients who met the case definition were included for retrospective review.
      RESULTS: P. aeruginosa pneumonia was community-acquired in 15 patients (94%). The
      majority of patients (94%) had a diagnosis of AIDS with a mean CD4 cell count of
      27 x 10(6)/l cells. Traditional risk factors for the development of P. aeruginosa
      were missing in most patients. Cavitary infiltrates were present on admission
      chest radiograph in eight patients (50%). An additional three patients (19%)
      presented with pulmonary infiltrates that cavitated subsequently. Clinical course
      was extremely varied with an in-hospital mortality of only 19%, but with an
      additional 25% of patients developing chronic or recurrent disease. CONCLUSIONS:
      Community-acquired pneumonia caused by P. aeruginosa occurs in patients with end
      stage HIV infection. The presence of cavitary pulmonary infiltrates on chest
      radiograph in a patient with a low CD4 count should raise suspicion of P.
      aeruginosa infection. Obvious risk factors for P. aeruginosa infection may be
      absent. While the initial mortality rate is lower than that observed in other
      immunocompromised hosts, the potential for chronic or recurrent infection should
      be recognized and patients should be followed closely.

PMID- 7818815
TI  - HIV-1 incidence determined retrospectively among drug users in Bangkok, Thailand.
AB  - OBJECTIVE: To measure trends in the incidence of HIV-1 infection among drug users
      in treatment at Thailand's largest drug detoxification unit. DESIGN: A
      retrospective cohort was established using computed, existing HIV-1 test results
      of 26,396 inpatients and outpatients admitted for 47,907 drug detoxification
      treatment courses from August 1987 to August 1992. METHODS: Matching of patient
      record numbers showed that 10,050 (38.1%) patients had been admitted two or more
      times during the period. From these, we selected a cohort of 7807 initially HIV
      negative patients. Subsequent seroconversions among them were assumed to have
      occurred with uniform probability throughout the interval between the last HIV
      negative and the first HIV-positive tests. RESULTS: There were 2311 (29.6%)
      seroconversions in the cohort. HIV-1 incidence among the 5974 (76.5%) who were
      injecting drug users (IDU) escalated from 20 new infections per 100 person-years
      (PY) of observation in 1987 to a peak of 57 per 100 PY in 1988, then gradually
      declining to a stable rate of about 11 per 100 PY during 1991 and 1992. Non-IDU
      (smokers, inhalers) constituted 683 (8.8%) of the cohort patients, and had HIV-1
      incidence rates varying from 0.2 to five per 100 PY. 'Mixed' drug users, defined
      as individuals reporting different routes of drug administration on different
      admissions, composed 1150 (14.7%) of cohort patients and had an HIV-1 incidence
      rate between that of IDU and non-IDU. Prevalence of HIV-1 seropositivity among
      all IDU increased rapidly, from about 1% in early 1988 to a peak of about 40% by
      early 1989, and has remained stable through 1992. CONCLUSIONS: Prevention efforts
      must continue for IDU, since recent annual HIV-1 incidence remains high at > 10
      per 100 PY. Such a high rate suggests that this group should be considered for
      HIV-1 vaccine efficacy trials. Stable HIV-1 prevalence can mask substantial
      incidence in a population with high turnover.

PMID- 7818816
TI  - Mother-to-child transmission of HIV-1 in Congo, central Africa. Congolese
      Research Group on Mother-to-Child Transmission of HIV.
AB  - OBJECTIVE: To assess the risk of mother-to-child transmission of HIV-1 in a
      central African population and to study maternal factors associated with
      perinatal transmission. DESIGN: Prospective cohort study of infants born to HIV-1
      positive women and controls born to HIV-1-negative women enrolled sequentially in
      two prenatal clinics and one maternity hospital in Brazzaville, Congo. SUBJECTS
      AND METHODS: A total of 118 exposed and 208 control infants were followed from
      birth for at least 2 years. Assessment of infection in children and computation
      of transmission rate were made according to the European Economic Community/World
      Health Organization Ghent guidelines (1992). RESULTS: The transmission rate was
      40.4% [95% confidence interval (CI), 30.7-50.1]. Maternal age, parity, history of
      adverse pregnancy outcome or history of decreased children were not associated
      with transmission. However, independently, women whose relationship with their
      infant's father was less than 1 year, or women who had symptoms of HIV-1 during
      pregnancy had an increased risk of transmission [adjusted odds ratios, 11.1 (95%
      CI, 2.4-50.2) and 10.3 (95% CI, 2.9-37.1), respectively]. CONCLUSION: The
      transmission rate observed in Congo is in the upper range of the rates reported
      in Africa. The uneven distribution of cofactors for perinatal transmission, such
      as the presence of symptoms of HIV disease during pregnancy, may explain some of
      the variation observed across studies.

PMID- 7818817
TI  - Mortality of intravenous drug users living in Milan, Italy: role of HIV-1
      infection. COMCAT Study Group.
AB  - OBJECTIVES: To study the trend in mortality from 1980 to 1991 in a cohort of 2432
      intravenous drug users (IVDU) enrolled between 1 November 1980 and 31 December
      1988. In addition, to evaluate the impact of HIV-1 infection on mortality.
      DESIGN: The vital status of people enrolled in the cohort was ascertained at
      registry offices of the municipalities of residence. Cause of death was
      determined by reviewing death certificates, clinical records and autopsy reports.
      Within the cohort, the causes of death of HIV-1-infected subjects were compared
      with those of subjects of undetermined serologic status. SETTING: Municipalities
      of the metropolitan area of Milan. RESULTS: The cohort was followed-up for 16415
      person-years (PY) and 413 deaths were observed up to 30 June 1991. Mortality was
      25.2 per 1000 PY, 20.5 times greater than that of the general population of the
      same age and sex. The leading cause of death was drug overdose, followed by AIDS
      (death rates 9.2 and 8.8 per 1000 PY, respectively). Mortality remained under 16
      per 1000 PY from 1981 to 1986, and then increased rapidly to 63.8 per 1000 PY in
      the first half of 1991. AIDS and overdose accounted for most of this increase,
      with AIDS becoming the leading cause of death from 1989. Mortality in HIV-1
      infected IVDU was higher than in IVDU as a whole (48.0 versus 19.9 per 1000 PY),
      and the difference was entirely due to AIDS and infectious diseases. CONCLUSION:
      The overall mortality rate and the mortality for AIDS and overdose were markedly
      higher than in other European countries in the same risk group. HIV-1 infection
      does not appear to affect the mortality for causes other than AIDS and infectious
      diseases.

PMID- 7818818
TI  - HIV infection among non-injecting drug users entering drug treatment, United
      States, 1989-1992. Field Services Branch.
AB  - OBJECTIVE: To describe HIV seroprevalence among non-injecting drug users (non
      IDU) entering sentinel drug treatment centers in the United States. DESIGN:
      Anonymous, blinded (unlinked) HIV seroprevalence surveys. SETTING: Sixty-eight
      sentinel drug treatment centers in 37 United States metropolitan areas.
      PARTICIPANTS: Consecutive sample of clients admitted to sentinel drug treatment
      centers from January 1989 through December 1992. Of 84,617 clients, 37,633
      (44.5%) had used illicit drugs but reported no injecting drug use since 1978.
      MAIN OUTCOME MEASURES: Center-specific, metropolitan area-specific, and national
      median HIV seroprevalence rates. RESULTS: National median center-specific HIV
      seroprevalence among non-IDU was 3.2% (range, 0-15.2%). Rates varied widely by
      geographic area. Median rates were highest in the northeast (5.6%; range, 0
      15.2%), intermediate in the south (3.4%; range, 0.6-8.0%), and generally lower
      throughout the rest of the country: midwest (1.3%; range, 0-3.1%) and west (1.8%;
      range, 0-14.5%). When stratified by treatment center, there were few
      statistically significant differences in seroprevalence among African Americans,
      Hispanics and whites. The median rate was 3.4% among men and 2.7% among women.
      Rates among non-IDU were lower than among IDU attending the same drug treatment
      centers, but consistently higher than among heterosexual patients attending
      sexually transmitted disease clinics in the same metropolitan areas. CONCLUSIONS:
      HIV seroprevalence among non-IDU entering drug treatment is high in many
      metropolitan areas. HIV prevention and education efforts in drug treatment
      centers should target sexual as well as drug-use risk reduction for all clients.

PMID- 7818819
TI  - Increasing age is associated with faster progression to neoplasms but not
      opportunistic infections in HIV-infected homosexual men.
AB  - OBJECTIVE: To characterize the associations of age and progression rates to AIDS
      defining neoplasms and opportunistic infections (OI) in HIV-infected homosexual
      men. METHODS: Data from 407 homosexual men with documented dates of HIV
      seroconversion participating in cohort studies from four geographic locations
      were merged. Kaplan-Meier and Cox proportional hazards analyses were conducted
      with respect to the association of age with time from seroconversion to the first
      AIDS-defining neoplasm and OI. RESULTS: Among the 407 participants, 139 (34%)
      were diagnosed with AIDS; 45 (11%) with neoplasms and 90 (22%) with OI. Older age
      at seroconversion was significantly associated with faster progression to
      neoplasms, but not to OI. For each 10-year increase in age the risk for neoplasms
      increased 1.65-fold [95% confidence interval (CI), 1.12-2.43], after adjustment
      for clinical treatments. For OI this risk estimate was 0.98 (95% CI, 0.72-1.34).
      CONCLUSIONS: Increasing age is associated with faster progression to AIDS
      defining neoplasms, but not with progression to OI. This has not been previously
      reported and may explain conflicting results in other studies among homosexual
      men that considered AIDS as a single entity. Our findings suggest that age and
      AIDS manifestations should be considered, particularly in the context of natural
      history studies, clinical trials and mathematical modelling.

PMID- 7818820
TI  - Prevalence of HIV-1 infection in urban, semi-urban and rural areas in Arusha
      region, Tanzania.
AB  - OBJECTIVE: To estimate HIV-1 prevalence among the adult population in the Arusha
      region, northern Tanzania. DESIGN: Cross-sectional study. METHODS: Clusters of 10
      households were randomly selected from urban, semi-urban and rural areas in the
      Arusha region. Informed verbal consent for participation in the interview and HIV
      1 test were obtained from the respondents. HIV-1 antibodies were tested using
      enzyme-linked immunosorbent assay (ELISA) and all ELISA-positive sera were
      confirmed using Western blot. Approximately 66.0% of the eligible registered
      adults (aged 15-54 years) participated in the interview, of whom 56.6% provided
      blood samples for HIV-1 testing. RESULTS: HIV-1 prevalence rates among the study
      population from the low and high socioeconomic status urban areas, semi-urban
      area and rural village were 10.7, 5.2, 2.2 and 1.6%, respectively. HIV-1
      prevalence was significantly higher among women (6.5%) than men (1.7%), and
      infection rates were consistently higher among women than men in all areas
      studied except in the rural village. Divorced and separated individuals had
      significantly higher HIV-1 prevalence (14.8%) compared with married and
      cohabiting individuals (4.0%). Significantly more individuals with multiple
      sexual partners reported regular condom use (19.3%) than those with one sexual
      partner (6.4%). CONCLUSION: HIV-1 prevalence in the Arusha region was higher
      among the urban population than among the rural population. Women living in urban
      areas with low socioeconomic status appeared to be associated with increased risk
      of HIV-1 infection.

PMID- 7818821
TI  - Family support for heterosexual partners in HIV-serodiscordant couples.
AB  - OBJECTIVE: To ascertain the extent of family member support to heterosexual HIV
      serodiscordant couples, and to identify associated sociodemographic and clinical
      characteristics. DESIGN: Discordant couples enrolled in a cohort study of
      heterosexual HIV transmission were interviewed with structured questionnaires to
      obtain sociodemographic data, family member awareness of HIV and perceived
      support from family members. Clinical characteristics were established by medical
      history, physical examination and laboratory tests. RESULTS: Awareness and
      support of family members were associated with sex of family member and HIV
      seropositivity, sex, education, and race of the partner. HIV-seropositive
      partners were more likely to have a sister aware than were HIV-negative partners
      (P = 0.01). More educated HIV-positive partners had fewer aware family members
      than less educated HIV-positive individuals (P = 0.02). Mothers of HIV-positive
      women were more often aware than mothers of all other partners (P = 0.04). Black
      HIV-negative partners had fewer aware family members than whites or Hispanics (P
      = 0.02). CONCLUSION: This research shows both encouraging and disturbing patterns
      of family awareness of HIV and support to serodiscordant partners.

PMID- 7818822
TI  - Surveillance of AIDS-defining conditions in the United States. Adult/Adolescent
      Spectrum of HIV Disease Project Group.
AB  - OBJECTIVE: To examine the reporting of AIDS-defining illnesses using two national
      surveillance systems. METHODS: Comparison of AIDS indicator diseases reported to
      the national AIDS reporting system (ARS) for AIDS cases diagnosed from January
      1990-December 1992 among individuals aged > 13 years in 10 metropolitan areas,
      with that observed in the Adult/Adolescent Spectrum of HIV Disease (ASD) project,
      a surveillance project that monitors the clinical diagnoses of HIV-infected
      individuals receiving medical care. RESULTS: In the 10 metropolitan areas, 39,265
      individuals with AIDS were reported to ARS, and 5969 with AIDS had medical record
      reviews as part of ASD. At initial AIDS diagnosis, the number of indicator
      diseases reported to ARS was almost identical to the number observed in ASD (mean
      number of diagnoses, ARS 1.3; ASD 1.2). However, ASD recorded a greater number of
      diagnoses over time than ARS (mean number of indicator diagnoses > 12 months
      after initial diagnosis, ASD 2.3; ARS 1.4). Conditions that typically occur late
      in the course of AIDS such as Mycobacterium avium infection and cytomegalovirus
      disease, were more frequently recorded by ASD than by ARS. CONCLUSION: ARS
      provides complete, population-based information on the frequency of AIDS-defining
      conditions at initial diagnosis. However, specialized surveillance projects such
      as ASD are needed to accurately describe subsequent AIDS-defining conditions.

PMID- 7818823
TI  - Reasons for the wide variation in reported rates of mother-to-child transmission
      of HIV-1.

PMID- 7818824
TI  - The epidemiology of HIV infection among injecting drug users and other risk
      populations in Thailand.

PMID- 7818825
TI  - Human T-cell leukaemia virus-I/II infection in Equatorial Guinea.

PMID- 7818826
TI  - Influenza immunization of HIV-1-infected patients does not increase HIV-1 viral
      load.

PMID- 7818827
TI  - HIV-1 Tat induces cytokine synthesis by uninfected mononuclear cells.

PMID- 7818828
TI  - Resistance to trimethoprim-sulfamethoxazole and sensitivity to pentamidine
      therapy in an AIDS patient with hepatosplenic pneumocytosis.

PMID- 7818829
TI  - Anal cancer in patients with HIV infection: a report of two cases without
      evidence of immunological dysfunction.

PMID- 7818830
TI  - Autoantibody-mediated platelet phagocytosis in SIV-infected macaques.

PMID- 7818831
TI  - The sharing of injecting paraphernalia among illicit drug users.

PMID- 7818832
TI  - Traditional healers in AIDS control.

PMID- 7818833
TI  - Infection with HIV, a risk factor for epidemic dysentery? A case-control study
      from Zambia.

PMID- 7818834
TI  - Vasodilators after myocardial infarction-ISIS IV.
AB  - Although small trials had suggested unrealistically high benefits from the use of
      vasodilators in acute myocardial infarction (MI), there was considerable
      statistical uncertainty about these benefits. Angiotensin-converting enzyme (ACE)
      inhibitors are clearly beneficial for left ventricular dysfunction after MI, but
      it was uncertain whether there was risk (from hypotension) for some patients in
      the early hours of an MI. After the GISSI-3 and International Studies of Infarct
      Survival (ISIS-4) trials it is now clear that nitrates are safe, but used
      routinely the small mortality reduction was not statistically significant. In
      ISIS-4 the results with magnesium were disappointing, with a worrying small
      excess mortality. On the other hand, routine use of ACE inhibitors in this early
      phase showed a statistically significant 5 to 10% reduction in mortality. There
      was greatest benefit in those with more obvious left ventricular damage. Since it
      is not easy to identify all such patients in the first hours, a policy of initial
      treatment of all, then later reassessment, is safe and would produce the greatest
      overall benefit.

PMID- 7818835
TI  - Mechanistic lessons from the SAVE Study. Survival and Ventricular Enlargement.
AB  - The Survival and Ventricular Enlargement (SAVE) study was designed to test the
      hypothesis that chronic use of the angiotensin-converting enzyme (ACE) inhibitor
      captopril in survivors of myocardial infarction with left ventricular dysfunction
      would prevent a further deterioration of ventricular function and thereby improve
      clinical outcome. The study did demonstrate that randomization to the ACE
      inhibitor resulted in improved survival and, specifically, lessened
      cardiovascular deaths. The prestudy rationale that less ventricular enlargement
      would be observed in ACE inhibitor treated patients was validated by an
      echocardiographic substudy. As anticipated, fewer patients treated with the ACE
      inhibitor went on to manifest the prespecified definitions of more overt
      congestive heart failure. Importantly, not only were the manifestations of
      congestive heart failure reduced, there were fewer fatal events subsequent to
      development of failure. Although this concept of attenuation of progressive
      remodeling leading to benefits was upheld, the study also yielded other
      observations to support the generation of new hypotheses to explain a component
      of the overall benefit of ACE inhibitor therapy. Particularly attractive, and
      supported by observation from the Studies of Left Ventricular Dysfunction (SOLVD)
      studies, is the reduction in myocardial infarction and subsequent death following
      myocardial infarction with chronic ACE inhibitor therapy. These clinical
      observations point to an important potentially modifiable interface between the
      renin-angiotensin system and the risk of experiencing a coronary atherosclerotic
      event.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7818836
TI  - Socioeconomic aspects of ACE inhibition in the secondary prevention in
      cardiovascular diseases.
AB  - Cardiovascular diseases are the leading causes of morbidity and mortality in the
      industrialized world and have become a major economic burden. Therefore, not only
      ethical and medical but also economic reasons suggest more intense efforts in
      primary and secondary prevention of cardiovascular and, especially, coronary
      artery disease. The prevention of the progression of heart failure and of the
      risks inherent in left ventricular dysfunction, including development of heart
      failure, reinfarctions, and death, are major cornerstones in the ambitious but
      economically balanced use of our resources. Major trials in chronic heart failure
      as well as the angiotensin-converting enzyme inhibitor pooling project in heart
      failure of all major studies have shown almost uniformly a reduction in
      hospitalizations attributable to slowing of the progression of the disease. In
      the Munich Mild Heart Failure Trial (MHFT) socioeconomic analysis confirmed the
      high economic burden of progression to the end-stages of disease: Patients with
      progressive heart failure had a four- to fivefold increase in hospital costs. The
      blunting of the progressive course of heart failure was effective enough to
      offset the costs of drug treatment with captopril in an analysis extrapolating
      the results of the socioeconomic analysis to the total trial population.
      Favorable results in preventive treatment of patients with asymptomatic left
      ventricular dysfunction, hypertension, and diabetic nephropathy also suggest that
      part of the additional costs of medication is outweighed by fewer
      hospitalizations and interventions. Thus in many cardiovascular diseases
      angiotensin-converting enzyme inhibitors have a favorable cost-benefit ratio and
      can be recommended for broader use.

PMID- 7818837
TI  - Integrated care concepts with angiotensin-converting enzyme inhibition:
      intervention for life. Introduction.

PMID- 7818838
TI  - Prognostic significance of microalbuminuria.
AB  - Diabetic nephropathy is the only increasing cause of renal failure in the Western
      world. It affects a large proportion of both insulin-dependent (IDDM) and non
      insulin-dependent diabetic (NIDDM) patients. A critical stage in the development
      of diabetic renal disease is the onset of microalbuminuria, defined as an albumin
      excretion rate of 30 to 300 mg/day. Microalbuminuria predicts progression to
      renal failure and early cardiovascular mortality in both IDDM and NIDDM patients.
      Microalbuminuria is associated with a constellation of other risk factors for
      small and large vessel damage which include raised blood pressure, poor glycemic
      control, plasma lipid and clotting factor abnormalities, left ventricular
      hypertrophy, and insulin resistance. Treatment with angiotensin-converting enzyme
      inhibitors corrects microalbuminuria and prevents progression to persistent
      proteinuria. Good blood glucose control significantly reduces the risk of
      progression from normoalbuminuria to microalbuminuria. The treatment of
      microalbuminuria appears highly cost-beneficial and substantially increases life
      expectancy. The development of microalbuminuria, for which all diabetic patients
      aged 12 to 70 years should be screened, should alert the physician to set in
      motion a program of assessment, monitoring, and correction of all risk factors
      for renal and cardiovascular disease.

PMID- 7818839
TI  - Angiotensin-converting enzyme inhibitors versus calcium antagonists in the
      progression of renal diseases.
AB  - In addition to factors such as protein intake or hyperlipidemia, hypertension
      contributes to the progressive deterioration of renal function in experimental
      animal models of renal disease, and has a prominent role in the imbalance of
      intrarenal hemodynamics. Reduction of arterial pressure was shown to alter the
      course of human chronic renal disease. In patients with diabetic as well as
      nondiabetic nephropathy, the lowering of proteinuria by angiotensin-converting
      enzyme inhibitors is greater than that observed with other antihypertensive drugs
      and appears to be independent of blood pressure control alone, whereas
      albuminuria may be unaffected or worsened during nifedipine treatment.
      Angiotensin-converting enzyme inhibitors may afford better protection than
      conventional treatment at various stages of diabetic nephropathy and prevent the
      evolution from incipient to overt nephropathy. In patients with nondiabetic renal
      disease, no unequivocal evidence exists for such a protective effect. In renal
      transplant recipients receiving cyclosporine, converting enzyme inhibitors and
      calcium antagonists are equally effective in the control of hypertension and both
      leave unaltered the glomerular filtration rate. It remains to be demonstrated,
      using adequate study designs, whether a particular class of agent is superior to
      another in patients with chronic renal disease.

PMID- 7818840
TI  - The Captopril Prevention Project (CAPPP): description and status.
AB  - The Captopril Prevention Project (CAPPP) is an ongoing prospective intervention
      study in 10,800 hypertensive patients in Sweden and Finland. Patients are
      randomized to treatment with either conventional antihypertensive therapy, ie,
      diuretics or beta-blockers, or the angiotensin-converting enzyme inhibitor
      captopril. The purpose of the CAPPP Study is to compare the two therapeutic
      alternatives with regard to cardiovascular mortality.

PMID- 7818841
TI  - Comparative study of the effect of ACE-inhibitors and other antihypertensive
      agents on proteinuria in diabetic patients.
AB  - Several studies during the past 15 years have shown that antihypertensive therapy
      with different types of drugs can reduce microalbuminuria or clinical proteinuria
      and retard the progression toward end-stage renal failure. However, some authors
      reported disparate renal protective effects of different antihypertensive drugs
      in diabetic animals and humans. In an attempt to resolve the controversy
      surrounding this possibility, previously we reported a meta-analysis of published
      studies in diabetics with microalbuminuria or overt proteinuria treated with
      conventional agents, angiotensin-converting enzyme (ACE) inhibitors, or calcium
      antagonists (Ca2+ antagonists). Here we present an updated meta-analysis of
      published studies in diabetics with microalbuminuria or clinical proteinuria
      (UProt), treated during > or = 4 weeks with ACE inhibitors, Ca2+ antagonists, or
      conventional therapy (diuretic and/or beta-blocker). Despite similar blood
      pressure (BP) reductions, UProt tended to decrease more on ACE inhibitors (on
      average -45%) than on conventional therapy (on average -23%) or Ca2+ antagonists
      other than nifedipine (on average -35%); in contrast, UProt tended to increase
      slightly on nifedipine (on average 5%, P < .05). On the basis of multiple
      regression analysis, ACE inhibitor-induced UProt changes correlated with BP
      changes (r = 0.77, P < .00001), averaged -28% at zero BP change, and varied 1.5%
      for each percent BP change. On conventional therapy, UProt and BP changes also
      correlated (r = 0.62, P < .005), but UProt began to decrease only after a BP
      reduction of > 5% and the slope was steeper (4% UProt change per percent BP
      change) than on ACE inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7818842
TI  - Therapeutic interventions in the progression of diabetic nephropathy.

PMID- 7818843
TI  - The use of zofenopril and fosinopril in acute myocardial infarction and carotid
      artery disease.
AB  - The potential of angiotensin-converting enzyme (ACE) inhibitors to protect the
      heart is a topic that has emerged recently as matter of scientific discussion.
      Experimental and clinical studies have shown the beneficial effects of ACE
      inhibitors on the metabolism, function, and structure of healthy and damaged
      hearts and these studies support the concept of both primary and secondary
      "cardioprotection" with these drugs. More recently, the prevention of
      atherosclerotic lesions has been demonstrated in animal models, extending the
      concept to a more general definition of "cardiovascular" protection with ACE
      inhibitors involving both the heart and the vessels. The potential role of ACE
      inhibitors on the primary prevention of atherosclerotic disease in humans is
      currently evaluated in PHYLLIS (Plaque HYpertension Lipid Lowering Italian
      Study), a multicenter clinical trial in which fosinopril sodium, a new ACE
      inhibitor, is administered to hypertensive patients with at least one
      uncomplicated carotid artery lesion. The primary aim of the study is to evaluate
      the effect of the drug on the long-term (3 years) progression of carotid artery
      atherosclerosis, noninvasively detected by B-mode ultrasound imaging. In addition
      to studies on primary prevention, some large clinical trials have been conducted
      to establish the role of ACE inhibitors on secondary prevention, in particular in
      patients with acute myocardial infarction (MI). The beneficial effect of these
      drugs is well established when administered in the subacute phase of acute
      MI.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7818844
TI  - Nuclear magnetic resonance studies of the structure of B50/neuromodulin and its
      interaction with calmodulin.
AB  - B50/neuromodulin is a neuronal phosphoprotein that is found in association with
      the inner membrane of nerve cells. In this work, we have studied the structure of
      bovine B50 in aqueous solution (pH 7.5) by 1H nuclear magnetic resonance (NMR)
      spectroscopy and our results indicate that B50 is an unstructured protein under
      these conditions. One-dimensional 1H-NMR titration studies of the interaction
      between B50 and calmodulin (CaM) have shown that B50 does not interact with (or)
      interacts very weakly with apo-CaM in solution; neither does B50 interact with
      Ca(2+)-CaM. These NMR data are consistent with an earlier observation that B50 is
      not capable of binding apo-CaM in vitro unless some nonionic detergent is
      present. We have also detected aromatic NMR peaks for a new posttranslational
      modification that might involve the His residues of the protein. The interaction
      of a 14-residue peptide (I38-L51) encompassing the CaM-binding domain of B50 with
      CaM was also studied by NMR. We have found from two-dimensional transferred
      nuclear Overhauser enhancement experiments that the B50 peptide binds weakly to
      apo-CaM in an alpha-helical conformation; the alpha-helix appears to be induced
      by the binding of the peptide to apo-CaM.

PMID- 7818845
TI  - Recloning of SV40 early gene transfected human endothelial cells repeatedly
      recovers subpopulations with low passage characteristics and morphologies.
AB  - Cultured human umbilical vein endothelial cells (HUVECs) are a valuable model for
      investigation of endothelial functions, but they enter senescence at low passage.
      Transfection of early passage HUVECs with the early genes of SV40 greatly extends
      the replicative potential of these cells, but eventually results in marked
      changes in growth, morphology, and biochemistry. Here we report a modified
      approach that appears to have overcome the problem of late passage decline after
      transfection. Plasmid pX-8 containing the SV40 early genes was transfected into
      passage four HUVECs. At passage five, these transfectants were cloned by limiting
      dilution and selected on the basis of both morphological and biochemical
      resemblance to their untransfected counterparts. Two clones that expressed factor
      VIII and in which the basal and the tumor necrosis factor-alpha inducible levels
      of interleukin 6 and endothelial adhesion molecules were normal were chosen.
      Vimentin and fibronectin distribution in these clones resembled untransfected
      cells. At passage 25, growth pattern changes were becoming evident, but recloning
      these late passage clones recovered numerous subclones of normal, cobblestone
      appearance. Two of these were further characterized and found to resemble their
      original parental clone by all of the biochemical criteria listed above. These
      subclones appeared to transform more rapidly than the parental clone, but
      repeated subcloning again rescued clones with normal morphologies and normal
      biochemical characteristics. We conclude that periodic recloning may indefinitely
      perpetuate lines that are useful equivalents of their original counterparts.

PMID- 7818846
TI  - Interaction of tissue plasminogen activator with a human endothelial cell 45
      kilodalton plasminogen receptor.
AB  - We have investigated the interaction of tissue plasminogen activator (tPA) with
      endothelial cell proteins of the human umbilical vein using the technique of
      ligand blotting. It was observed that tPA interacted with a 45-kilodalton (kDa)
      endothelial cell protein which appeared to be similar to the 45-kDa plasminogen
      receptor. Binding of tPA to the 45-kDa protein could be inhibited by excess cold
      tPA. Moreover, excess lysine could inhibit the binding of tPA to the 45-kDa
      protein in both coincubation and reversibility experiments. These studies
      indicated that like plasminogen, tPA interacts with the 45-kDa protein in a
      kringle-dependent and specific manner. To confirm that tPA and plasminogen are
      interacting with the same protein, we investigated the effect of excess cold
      plasminogen on tPA binding and excess cold tPA on plasminogen binding in
      reversibility experiments. It was observed that binding of tPA to the 45-kDa
      protein was reduced by plasminogen and vice versa. In addition, the 45-kDa
      protein did not cross-react with antibodies to annexin II, a 40-kDa protein that
      binds plasminogen and tPA. These latter properties distinguish the 45-kDa
      receptor from plasminogen/tPA-binding proteins described by others. Therefore,
      the above studies suggest that the 45-kDa protein represents a unique
      plasminogen/tPA receptor on human venous endothelial cells.

PMID- 7818847
TI  - Analysis of the lipoprotein binding site of rat liver membranes.
AB  - Intermediate density lipoproteins (IDL) were shown to bind to high- and low
      affinity binding sites on rat liver membranes. The low-affinity sites were named
      lipoprotein binding sites (LBS), since they bind all classes of lipoproteins.
      This study was undertaken to further characterize the interaction of 125I
      labelled IDL with the LBS of rat liver membranes to determine the chemical nature
      of the LBS. We found that the binding of IDL to the LBS is insensitive to EDTA
      and sensitive to heparin and that it is present on plasma membranes. Also,
      membranes were pretreated with various enzymes that have an effect on the
      membrane constituents, and the activity of the LBS on these treated membranes was
      determined. Our results reveal that the LBS of rat liver membranes is insensitive
      to heparinase I, chondroitinase ABC, and phospholipase C, while it is partially
      sensitive to phospholipase A2 and sensitive to proteases and heat. Rat liver
      membrane proteins were solubilized with Triton X-100, reconstituted in liposomes,
      and analyzed for their ability to bind lipoproteins. 125I-labelled IDL were shown
      to bind to high- and low-affinity sites that are similar, in affinity and
      specificity, to the ones observed with intact rat liver membranes, indicating
      that a LBS activity is detectable on these liposomes. We found that the binding
      capacity of low-affinity sites in liposomes containing either no protein or
      containing proteins solubilized from Escherichia coli membranes is five times
      weaker than low-affinity sites in liposomes containing liver membrane proteins.
      Thus, a protein solubilized from rat liver membranes has LBS activity when
      reconstituted in liposomes. Taken altogether our results provide new information
      on the binding of IDL to the LBS and indicate that the LBS activity is in part
      mediated by a protein. Thus, the LBS appears to be a bona fide receptor.

PMID- 7818848
TI  - Cyclosporin treatment alters protein phosphorylation in kidney membranes.
AB  - Phosphorylation, protein carboxyl methylation, and ADP-ribosylation were assayed
      in renal basolateral membranes and brush border membranes isolated from rats
      treated by subcutaneous administration of 5 or 10 mg/(kg.day) of cyclosporin A
      (CsA) for 10 days to investigate potential alterations in signal transduction in
      kidney cortex. Protein carboxyl methylation of class II measured in membranes and
      in cytosolic fraction was not affected by CsA treatment. ADP-ribosylation
      performed in the presence of pertussis or cholera toxin was also similar in
      control and treated rats. However, changes in phosphorylation of endogenous
      substrates were observed in membranes and cytosol isolated from rats treated with
      10 mg/(kg.day) of CsA. Phosphorylation was increased for two brush border
      membrane proteins (56 and 77 kilodaltons (kDa)) by 47 and 24% and for two
      basolateral membrane proteins (51 and 80 kDa) by 28 and 29%, respectively. In the
      cytosolic fraction, phosphorylation of two proteins (31 and 65 kDa) was increased
      by 37% and that of 25- and 43-kDa proteins was reduced by 29%. Protein kinase A,
      protein kinase C, and tyrosine protein kinase activities were also determined in
      membranes. Increases in protein kinase C and tyrosine protein kinase activities
      were observed in basolateral membranes, but not in brush border membranes after
      cyclosporin A administration. Endogenous substrates for tyrosine kinase were also
      detected with an antiphosphotyrosine (PY20) monoclonal antibody. Densitometric
      analysis indicated that the phosphorylation of three proteins of high molecular
      masses (61, 132, and 183 kDa) was stimulated by CsA in basolateral
      membranes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7818849
TI  - A low molecular weight peptide from snow mold with epitopic homology to the
      winter flounder antifreeze protein.
AB  - Evidence for a small size protein (ca. 3500 kDa) exhibiting epitopic homology to
      the Atlantic winter flounder antifreeze protein (AFP) is found in the snow molds
      Coprinus psychromorbidus, Myriosclerotinia borealis, and Typhula incarnata. The
      protein shows strong cross-reactivity with antisera specific for the flounder
      AFP. Preliminary studies suggest that the protein is synthesized in response to
      lowering the culture temperature, and that it is membrane associated and,
      therefore, may function in an analogous capacity to the fish AFP. Also, the
      protein is shown to have antifreeze properties as determined by nuclear magnetic
      resonance microimaging experiments.

PMID- 7818850
TI  - Characterization of a chymotrypsin-like hydrolytic activity in the opossum kidney
      cell.
AB  - To characterize a chymotrypsin-like hydrolytic activity in the cell surface
      membranes of intact opossum kidney (OK) cells, we partially purified a protease
      from the membrane fractions of OK cells using Suc-Leu-Leu-Val-Tyr-MCA (Suc,
      succinyl; MCA, 4-methylcoumaryl-7-amide), a synthetic substrate for chymotrypsin,
      as the substrate. The semipure enzyme showed seryl chymotrypsin-like
      characteristics such as preferential hydrolysis of Suc-Leu-Leu-Val-Tyr-MCA and
      inhibition by phenylmethylsulfonyl fluoride, diisopropylfluorophosphate, and
      chymostatin. However, it clearly differed from alpha-chymotrypsin in its weak
      ability to hydrolyze Suc-Ala-Ala-Pro-Phe-MCA and in its high molecular mass (250
      300 kDa). The enzyme also had an endopeptidase-like activity in that it cleaved
      human parathyroid hormone(1-84) at the Leu(37)-Gly(38) and Arg(52)-Lys(53) bonds.
      These results suggest that a high molecular mass chymotrypsin-like endopeptidase
      with unique characters is present in the membrane fractions of OK cells.

PMID- 7818851
TI  - Neutral endopeptidase (EC 3.4.24.11): constructed molecular forms show new angles
      of an old enzyme.

PMID- 7818852
TI  - Characterization of parvalbumin cDNA clones and gene expression in normal and
      dystrophic mice of strain 129 ReJ.
AB  - Parvalbumin is a calcium-binding protein found in fast-twitch skeletal muscles
      and selected cells in the brain. In several dystrophic mutants in the mouse, the
      parvalbumin content of skeletal muscles and brain is reduced and this deficiency
      appears to correlate with the inability of these mice to handle enhanced calcium
      uptake associated with the dystrophic process. In this study, two overlapping
      cDNA clones of 392 and 1268 base pairs were isolated from a mouse cDNA library in
      lambda gt11, characterized, and used as probes to study the involvement of the
      parvalbumin gene and its expression in various tissues of dystrophic mice of
      strain 129 ReJ. Southern blot analyses of restriction fragments of genomic DNA
      from normal and dystrophic mice indicate the same number and size of parvalbumin
      specific gene fragments observed by other researchers, suggesting that the size
      of the Pva gene is the same in both normal and dystrophic mice of strain 129 ReJ.
      Northern blot analyses of total RNA from hind-limb muscles using cloned
      parvalbumin cDNA as probes revealed an abundant 800-nucleotide mRNA with lesser
      amounts of a 1000-nucleotide mRNA transcript in both normal and dystrophic mice
      of strain 129 ReJ. The amount of these mRNAs was reduced by 65-77% in dystrophic
      muscles preparations and was similar to the levels of beta-actin mRNA in these
      animals. These results suggest that parvalbumin gene expression is not down
      regulated in dystrophic mice of strain 129 ReJ.

PMID- 7818853
TI  - Gene expression after resumption of development of Artemia franciscana
      cryptobiotic embryos.
AB  - The steady-state levels of six different mRNAs have been studied during Artemia
      franciscana development. Some of these mRNAs are present in the cryptobiotic
      cyst, like those coding for cytoplasmic actins, sarcoplasmic/endoplasmic
      reticulum Ca(2+)-ATPase, and the Na+, K(+)-ATPase alpha-subunit isoform coded by
      the clone pArATNa136. The expression of these mRNAs is markedly induced during
      cyst development. A small increase in mRNA levels can be observed for some genes
      at very early stages of development (2 h). The main increase is observed between
      4 and 16 h of development for all these genes, although the time course of mRNA
      accumulation is different for each one of the genes studied. Some other genes,
      like those coding for muscle actin (actin 3) or the Na+, K(+)-ATPase alpha
      subunit isoform coded by the cDNA clone alpha 2850, are not expressed in the cyst
      before resumption of development and their expression is induced after 10 or 6 h
      of development, respectively. These data on the kinetic of mRNA accumulation
      provide the information required to determine transcriptionally active
      developmental stages, necessary to study in more detail the mechanisms of
      transcriptional regulation during activation of cryptobiotic cysts and resumption
      of embryonic development.

PMID- 7818854
TI  - A nuclear magnetic resonance study of the DNA-binding affinity of Cro repressor
      protein stabilized by a disulfide bond.
AB  - The structure, dynamics, and DNA-binding characteristics of wild-type and cross
      linked Cro repressors are compared by using circular dichroism (CD) and nuclear
      magnetic resonance (NMR) spectroscopies. The Cro repressor is a small dimeric DNA
      binding protein from bacteriophage lambda. Replacement of valine-55 by cysteine
      in the dimer interaction region of each monomer subunit results in the
      spontaneous formation of a disulfide cross-link between the subunits. Two
      dimensional nuclear Overhauser effect spectroscopy and CD data show the variant
      has nearly the same conformation as the wild-type protein. However, by monitoring
      the CD band at 222 nm, the cross-linked protein is shown to have a heat
      denaturation midpoint temperature of 67 degrees C, whereas the wild-type protein
      has a melting temperature of about 47 degrees C. Using 1H-NMR to follow the
      denaturation by heat, the same melting temperature is observed for wild-type Cro
      (47 degrees C), but a much lower melting temperature is seen for V55C Cro (58
      degrees C). This suggests that between 58 and 67 degrees C the cross-linked
      protein exists in a molten globule state with the alpha-helices mainly intact,
      but without the interaction of chemical groups that cause spectral dispersion.
      Binding parameters for interaction of the proteins with DNA were obtained by
      observing the NMR spectrum for the imino protons of a 10 base-pair half-operator
      DNA and titrating in protein. The cross-linked protein binds DNA (Kd = 160
      microM) about eight times more weakly than the wild-type protein (Kd = 19
      microM). Adjustments in protein structure, necessary to form a tight protein-DNA
      complex, appear to be hindered by a loss in protein flexibility caused by the
      intersubunit cross-link.

PMID- 7818855
TI  - The G. W. Harris Prize Lecture. The gut endocrine system and its control.

PMID- 7818856
TI  - The relationship between blood flow and diameter in the iliac artery of the
      anaesthetized dog: the role of endothelium-derived relaxing factor and shear
      stress.
AB  - The quantitative relationship between, increase in blood flow and arterial
      diameter was determined in an anaesthetized dog preparation (pentobarbitone,
      induction 30 mg kg-1 i.v., maintenance 3 mg kg-1 i.v. every 30 min). Changes in
      external iliac artery diameter were measured using piezoelectric ultrasound
      transducers capable of measuring diameters within the range of 2-20 mm with a
      resolution of +/- 0.005 mm. The diameter of the artery was measured at two sites,
      at one of which the endothelium was damaged using a balloon angioplasty catheter.
      Increases in blood flow were brought about by a combination of vasodilatation and
      cardiac stimulation (intra-arterial administration of acetylcholine, downstream
      to the sites of diameter measurement, and electrical stimulation of the left ansa
      subclavia), thereby preventing large changes in blood pressure. The effects of
      both transient and maintained increases in blood flow on mean arterial diameter
      in the section of artery with intact endothelium were measured. Transient
      increases in mean flow from 147 +/- 0.21 to 611 +/- 80.0 ml min-1 caused
      increases in diameter of 0.12 +/- 0.02 mm from a control of 5.42 +/- 0.19 mm. The
      mean delay between maximum flow and maximum diameter was 24.51 +/- 1.1 s and the
      half-time for the return to control diameter was 82.0 +/- 9.6 s, compared with
      12.1 +/- 1.5 s for the return to control flow. Maintained (3-4 min) increases in
      mean blood flow (from 104.7 +/- 15.1 to 694.7 +/- 135.1 ml min-1) produced larger
      increases in diameter of 0.48 +/- 0.30 mm from a control diameter of 4.89 +/-
      0.12 mm. These changes in diameter were abolished by N omega-nitro-L-arginine
      methyl ester (L-NAME. 10-100 mg kg-1 i.v.). In the section of artery with damaged
      endothelium, changes in diameter were relatively small and associated with small
      changes in blood pressure. This effect of a nearly 7-fold increase in flow on
      arterial diameter is dependent upon the integrity of the endothelium and the
      release of endothelium-derived relaxing factor and causes a 29% reduction in
      calculated boundary wall shear stress.

PMID- 7818857
TI  - The effect of frusemide on oxytocin-induced contractions of the rat myometrium.
AB  - Oxytocin-induced contractions of isolated strips of oestradiol-treated rat
      myometrium were found to be affected by exposure to the diuretic frusemide. At a
      concentration of 20 microM. frusemide transiently increased the force of
      contraction over a period of approximately 10 min. After this time there was a
      progressive fall in contractile force. At a higher concentration of 200 microM,
      only the progressive fall in force was seen until contractions were completely
      abolished. Frusemide has been reported to increase the activity of cAMP
      phosphodiesterase in tissue extracts from oestradiol-treated rat myometrium.
      Therefore, the changes in contraction due to exposure to frusemide may be a
      reflection of the changes in intracellular cAMP resulting from a stimulation of
      cAMP-phosphodiesterase activity. In support of this idea, addition of dibutyryl
      cAMP was found to partially restore contractions after frusemide treatment. These
      data suggest that frusemide may be a useful tool in the manipulation of tissue
      cAMP levels in order to determine the different roles of cAMP in the oestradiol
      treated rat myometrium.

PMID- 7818858
TI  - Effects of intracellular pH on calcium currents and intracellular calcium ions in
      the smooth muscle of rabbit portal vein.
AB  - In smooth muscle cells freshly dispersed from the rabbit portal vein, effects of
      intracellular pH (pHi) on Ca2+ channel currents were studied with the whole-cell
      clamp method using nystatin in the pipette. pHi was modified with ammonium
      chloride (NH4Cl) and propionate. Changes in intracellular Ca2+ concentration
      ([Ca2+]i) and pHi were also measured with the fluorescent indicator fura-2 and a
      pH-sensitive dye, respectively, together with the mechanical response in intact
      tissues. Intracellular alkalinization caused by an application of NH4Cl (20 mM)
      markedly potentiated and acidification caused by propionate (20 mM) inhibited
      inward Ca2+ channel currents, without much change in the kinetics. Tension
      development induced by 60 mM K- was inhibited by NH4Cl (20 mM) and potentiated by
      propionate (20 mM), whereas the peak [Ca2+]i level reached during K+ contracture
      was reduced in the presence of NH4Cl and increased in the presence of propionate.
      It was concluded that the modification of Ca2+ channel currents caused by pHi is
      not directly related to the effects of pHi on the mechanical response to excess
      K+. The direct effects of pHi on [Ca2+]i and on contractile machinery are
      considered to be mainly responsible for the mechanical effect of pHi.

PMID- 7818859
TI  - Developmental and gestational changes of phosphoethanolamine and taurine in rat
      brain, striated and smooth muscle.
AB  - Concentrations of taurine and phosphoethanolamine in rat smooth (intestinal and
      uterine), skeletal and cardiac muscle, and brain have been determined, using high
      performance liquid chromatography (HPLC), to examine possible interrelationships
      in their tissue content. Concentrations were determined in fetal and neonatal
      samples, as well as in adult tissue, to investigate whether phosphoethanolamine
      and taurine levels are influenced by developmental state. The effect of
      gestational state was also studied. A marked decrease in cerebral
      phosphoethanolamine concentration during development was found together with a
      concomitant decrease in striated muscle but not in the two smooth muscles
      studied. A rise in uterine phosphoethanolamine during the early postpartum period
      confirmed previous NMR data. This occurred only in the uterus, suggesting it is
      specific to the process of involution within the myometrium. Taurine
      concentrations showed no consistent pattern of change with postnatal development.
      In adult animals, the highest levels of taurine were found in cardiac muscle.
      Pregnancy was associated with a fall in taurine concentration in all tissues,
      suggesting an influence of steroid hormones. As taurine is cotransported with Na+
      in many systems it may be related to the increased water retention seen in
      pregnancy. It is concluded that marked changes in phosphoethanolamine and taurine
      levels occur during development and gestation, but that the changes are not
      interdependent, i.e., the changes are tissue specific.

PMID- 7818860
TI  - Primary and secondary afferent discharges from the same spindle during chain
      fibre contraction in cat tenuissimus muscle.
AB  - Pairs of Ia and II afferent fibres supplying primary and secondary endings lying
      in the same tenuissimus spindles were prepared in barbiturate anaesthetized cats
      in order to compare the variability in the rhythm of discharge of the two endings
      during responses elicited by the contraction of different intrafusal muscle
      fibres, especially by chain fibres. In these spindles, the intrafusal muscle
      fibres supplied by single static gamma-axons were identified with a recently
      developed technique based on the types of primary ending activation observed
      during gamma stimulation at 30 and 100 stimuli/s. The responses of the secondary
      endings to contraction of chain fibres either alone or with bag2 fibres were
      smaller and much more regular than the responses of the primary endings lying in
      the same spindles. This difference is probably related to the position of
      secondary endings along the intrafusal muscle fibres and to the mechanical
      properties of the muscle fibre regions on which the terminals lie. The dynamic
      properties of the encoding site of primary afferent impulses probably contribute
      to the difference. The different degrees of variability observed among secondary
      ending responses elicited either by chain fibres alone or by chain and bag2
      fibres are not related to the type of activated intrafusal muscle fibres.

PMID- 7818861
TI  - The intracortical neuronal connectivity subserving focal epileptiform activity in
      rat neocortex.
AB  - In the anaesthetized rat, regions of the somatosensory cortex have been subpially
      isolated, leaving intact the cortical blood supply and the connectivity via the
      white matter. Application of penicillin or strychnine into layer IV of intact
      cortex resulted in enhancement of amplitude and prolongation of evoked potentials
      together with the appearance of spontaneous epileptiform discharges. Within a
      partially isolated region of cortex, spontaneous and evoked potentials occurred
      as in normal cortex, but application of convulsant drug resulted in no changes in
      evoked potentials and in no spontaneous spiking. With incisions for which the
      surface profile measured 0.9 x 0.9 mm, full-depth isolation resulted in
      interruption of the propensity for epilepsy, whereas half-depth incisions left
      epileptic manifestations unimpaired. With the surface profile measuring 0.5 x 0.5
      mm, half-depth isolation was sufficient to prevent epileptic activity. Results
      from isolated regions of various geometries and sizes indicated that the ability
      of cortical neurones to generate epileptic activity depends on the amount of
      connectivity with surrounding cortex. The propensity of cortex to become
      epileptic is thus a mass action effect and the 'epileptic neuronal aggregate' is
      operationally different from anatomically based modular organizations such as
      thalamo-cortical or cortico-cortical columns. In the small barrel field of the
      somatosensory cortex, partial isolations that prevented the appearance of
      spontaneous epileptiform spiking contained many barrels, indicating that a single
      thalamo-cortical module contains insufficient inherent lateral connectivity to
      support epileptiform activity. Theoretical considerations indicated that the
      excitability of a neurone depends both on its monosynaptic connections with other
      neurones and on the connectivity of these latter with neurones further afield.
      The interruption of epileptiform activity by partial isolation could be mimicked
      by a computer model in which connectivity was mediated via short synaptic paths.
      The model exhibited self-sustaining synchronized neural activity that could be
      prevented by interruption solely of polysynaptic paths.

PMID- 7818862
TI  - Acid-base transport systems in a polarized human intestinal cell monolayer: Caco
      2.
AB  - Acid-base transport systems have been incompletely characterized in intact
      intestinal epithelial cells. We therefore studied the human cell line Caco-2,
      cultured on Teflon membranes to form confluent monolayers with apical microvilli
      on transmission electron microscopy and progressive enrichment in microvillar
      hydrolases. Monolayers (16- to 25-day-old), loaded with the pH-sensitive dye
      BCECF-AM (2',7'-bis (carboxyethyl)-5-carboxyfluorescein), were mounted in a
      spectrofluorometer cuvette to allow selective superfusion of apical and
      basolateral surfaces with Hepes- or HCO(3-)-buffered media. Intracellular pH
      (pHi) was measured by dual-excitation spectrofluorimetry; calibration was with
      standards containing nigericin and 110 mM K+ corresponding to measured
      intracellular [K+] in Caco-2 cell monolayers. In HCO(3-)-free (Hepes-buffered)
      media, bilateral superfusion with 1 mM amiloride or with Na(+)-free media
      reversibly inhibited pHi recovery from an intracellular acid load (NH4Cl pulse)
      by 86 and 98% respectively. Selective readdition of Na+ to the apical or
      basolateral superfusate also induced a pHi recovery, which was inhibited by
      ipsilateral but not by contralateral amiloride (1 mM). The pHi recovery induced
      by apical Na+ readdition had a Michaelis constant (Km) for Na+ of 30 mM and a
      relatively high inhibitor constant (Ki) for amiloride of 45.5 microM. Initial pHi
      in HCO(3-)-buffered media was lower than in the absence of HCO3- (7.35 vs. 7.80).
      pHi recovery from an acid load in HCO3- was Na- dependent but was inhibited only
      18% by 1 mM amiloride. The amiloride-independent pHi recovery was inhibited 49%
      by pre-incubation of cells in 5 mM DIDS (4,4'-diisothiocyanatostilbene-2,2'
      disulphonic acid). These data suggest that Caco-2 cells possess: (a) both apical
      and basolateral membrane Na(+)-H+ exchange mechanisms, the apical exchanger being
      relatively resistant to amiloride, similar to apical Na(+)-H+ exchangers in
      several normal epithelia; and (b) a Na(-)-dependent HCO3- transport system,
      either Na(+)-HCO3- cotransport or Na(-)-dependent Cl(-)-HCO3- exchange.

PMID- 7818863
TI  - A new approach to measuring transepithelial potentials in the bovine lens reveals
      a chloride-dependent component.
AB  - A new approach was used to measure anterior and posterior potentials and
      resistances of the bovine lens. Segments of the anterior, central and posterior
      lens were studied by mounting a disc of tissue from either the front or the back
      of the lens in a double chamber. At 35 degrees C the isolated anterior epithelial
      preparation exhibited a high potential of 9 mV and a low resistance of 279 omega
      cm2. The lens epithelium can therefore be classified as a 'leaky' or low
      resistance epithelium. Amiloride, benzamil and furosemide (frusemide) all reduced
      the anterior transepithelial potential and increased the resistance, amphotericin
      B (aqueous side) abolished the potential, whereas SITS (4-acetamido-4'
      isothiocyanatostilbene-2,2'-disulphonic acid) had no effect. The posterior lens
      preparation was found to have a 'transepithelial' of -4 mV. This potential and a
      proportion of the anterior potential were not sensitive to ouabain, amiloride,
      furosemide, Na+ removal or raised K+, but were abolished by lowering [Cl-] and
      reduced by the Cl- channel blocker NPPB. We conclude that chloride plays a
      significant role in the maintenance of transepithelial potentials at both the
      anterior and posterior surfaces of the lens.

PMID- 7818864
TI  - Sodium and chloride transport across the rumen epithelium of cattle in vitro:
      effect of short-chain fatty acids and amiloride.
AB  - Isolated mucosal sheets of cattle rumen were studied in vitro in Ussing chambers
      using a computer-controlled voltage clamp. Unidirectional fluxes of Na+ and Cl-
      were measured in standard (short-chain fatty acid (SCFA)-free) or SCFA-containing
      Ringer solution under zero voltage clamp conditions. Net NaCl absorption was
      observed under zero voltage clamp conditions, was stimulated by SCFAs and was not
      reduced by 1 mmol l-1 amiloride, although short-circuit current was significantly
      reduced by this concentration of the blocker. A constant coupling ratio of Na+
      and Cl- absorption was observed.

PMID- 7818865
TI  - Interaction of aldosterone and oxytocin to influence renal sodium excretion in
      rats.
AB  - The possibility of an interaction between oxytocin and aldosterone to influence
      renal Na+ excretion was investigated in Inactin-anaesthetized male Sprague-Dawley
      rats. Endogenous plasma concentrations of aldosterone were suppressed by either
      adrenalectomy or bicarbonate infusion. The effects of 2 h intravenous
      administration of oxytocin (0.04 pmol/min) and/or aldosterone (42 pmol/min) on
      renal Na+ handling were studied in 0.077 M NaCl-infused adrenalectomized (Adx)
      rats and groups of intact animals that were infused with 0.077 M NaHCO3.
      Aldosterone alone significantly (P < 0.01) reduced Na+ excretion from
      pretreatment peak value of 5.0 +/- 1.0 to 1.5 +/- 0.4 mumol/min in Adx animals (n
      = 8) and 9.2 +/- 1.2 to 5.2 +/- 1.2 mumol/min in NaHCO3-infused rats (n = 8) by 2
      h after the start of administration. However, combined administration of
      aldosterone and oxytocin was associated with a significantly (P < 0.01) increased
      Na+ excretion rate from a peak pretreatment value of 6.8 +/- 0.7 mumol/min to a
      peak value of 11.5 +/- 1.1 mumol/min by 1 h 40 min after the start of treatment
      in Adx rats (n = 7). In bicarbonate-infused rats (n = 8) Na+ excretion rose
      within 20 min of the start of treatment from a pretreatment peak of 9.0 +/- 0.8
      mumol/min to a peak value of 13.5 +/- 0.8 mumol/min in response to combined
      hormone administration. In conclusion, we have shown that concomitant
      administration of aldosterone and oxytocin increased the rate of excretion of Na+
      in two different preparations, which supports the idea of an interaction between
      the steroid and oxytocin to promote Na+ loss.

PMID- 7818866
TI  - Activation of the vasopressin-sensitive water permeability pathway in the toad
      bladder by N-ethyl maleimide.
AB  - Vasopressin stimulates transepithelial water flow in the toad urinary bladder. We
      report here that N-ethyl maleimide (NEM) (0.1 mM) produces a similar increase in
      osmotic water flow when applied to the mucosal surface of the tissue. NEM-induced
      water flow is sensitive to inhibitors of hormone-induced water flow, including
      serosal acidification, or exposure to quinidine or cytoskeleton-disruptive drugs.
      NEM-induced water flow is additive with that induced by a submaximal, but not a
      maximal, dose of vasopressin. The response to mucosal NEM is not reversed on
      removal of the reagent, but established NEM-induced water flow can be inhibited
      by serosal acidification or quinidine. Like vasopressin, mucosal NEM induces the
      appearance of fusion profiles and intramembranous particle aggregates (putative
      water channels) in the apical plasma membrane of the granular cells, and the
      incidence of particle aggregates correlates with water flow. NEM does not cause
      an increase in intracellular cAMP. Our data suggest that NEM stimulates
      transepithelial water flow by irreversibly activating cellular mechanisms
      normally triggered by vasopressin, hence causing the insertion of water channels.

PMID- 7818867
TI  - Differentiation of the peripherally mediated from the centrally mediated
      influences of adenosine in the rat during systemic hypoxia.
AB  - In two groups of Saffan-anaesthetized, spontaneously breathing rats we have
      attempted to identify the peripheral influences of adenosine in mediating the
      responses evoked by hypoxia by using an adenosine receptor antagonist, 8
      sulphophenyltheophylline (8-SPT, 20 mg kg-1 i.v., Group 1) and adenosine
      deaminase (ADA, 500 units in 0.04 ml infused into the tail artery for 10 min,
      Group 2); neither of these drugs crosses the blood-brain barrier. Recordings were
      made of respiration, heart rate, arterial pressure, blood flow and vascular
      conductance in the femoral artery, with ankle ligated (FBF and FVC, respectively)
      and in the carotid artery with all branches except the internal carotid ligated
      (CBF and CVC, respectively, Group 1 only) in order to indicate responses in
      skeletal muscle and cerebral vasculature. Hypoxia (breathing 8 or 10% O2 for 10
      min) evoked an increase followed by a secondary decrease in respiration,
      tachycardia followed by secondary bradycardia, a fall in arterial pressure, an
      increase in FVC and CVC and an increase, followed by a decrease, in CBF. Neither
      8-SPT nor ADA had any significant effect on the secondary decrease in
      respiration. The secondary bradycardia was unaffected by 8-SPT, but abolished by
      ADA. Both drugs reduced the fall in arterial pressure and the increase in FVC; 8
      SPT had no significant effect on the increase in CVC, but CBF no longer fell with
      arterial pressure. We propose that adenosine contributes to the hypoxia-induced
      fall in arterial pressure by causing vasodilatation in skeletal muscle and
      possibly by causing bradycardia by a direct action on the heart; other evidence
      suggests that adenosine contributes to the secondary decrease in respiration by
      acting on central respiratory neurones. The possibility that the fall in arterial
      pressure and the secondary falls in CBF, respiration and heart rate, can become
      interdependent in a positive feedback manner is discussed.

PMID- 7818868
TI  - Indirect measurement of saliva secretion in sheep fed diets of different
      structures and the effect of such diets on ruminal fluid kinetics and
      fermentation pattern.
AB  - Four Suffolk x Dorset sheep were allocated in a 4 x 4 Latin square design and
      received a hay-barley-molasses diet in one of four different physical structures:
      (1) pelleted; (2) pelleted:chopped (60:40); (3) chopped:pelleted (60:40); or (4)
      chopped. The animals were penned individually and the diet was restricted to
      provide 20 g of dry matter (DM) per kilogram live weight daily. The effects of
      the diets on rumen fluid kinetics, fermentation pattern and microbial nitrogen
      (MN) supply were examined. Saliva secretion was estimated using an indirect
      method based on water balance in the rumen. When the animals were fed the chopped
      diet, the salivation rate, rumen fluid volume and rumen liquid outflow were all
      increased significantly (P < 0.05 to P < 0.01). No consistent effect of dietary
      structure on rumen fluid dilution rate, purine derivative (PD) excretion or MN
      supply was observed. Dietary structure had no effect on the rumen fermentation
      pattern, digestibility of DM or nitrogen.

PMID- 7818869
TI  - An explanation for residual increased tension in striated muscle after stretch
      during contraction.

PMID- 7818871
TI  - A linear relationship between ATP degradation and fatigue during high-intensity
      dynamic exercise in rat skeletal muscle.
AB  - The relationship between changes in work output (fatigue) and metabolite
      concentrations was measured in rat skeletal muscle during the course of dynamic
      exercise (10 s). After 4 s, work output decreased rapidly to approximately 30% at
      8 s. In contrast to the changes in phosphocreatine and lactate, the change in ATP
      concentration paralleled the reduction in work output. A strong linear
      relationship (r = 0.95) was found between the relative decrease in ATP and the
      extent of fatigue. Possible mechanisms underlying this relationship are
      discussed.

PMID- 7818870
TI  - Calcium currents and contraction in frog atrial trabeculae.
AB  - The properties of two types of calcium current (ICa(T) and ICa(L)) and their
      relationship with contraction were studied in isolated frog atrial trabeculae
      using the double mannitol gap technique. In Ringer solution containing TTX the
      calcium currents observed are similar to the ICa(T) and ICa(L) found in single
      frog atrial cells. The results obtained by using inorganic calcium channel
      blockers have shown that the phasic contraction appears only when ICa(T) and
      ICa(L) are simultaneously present. It is proposed that ICa(T) loads the
      sarcoplasmic reticulum (SR) while ICa(L) triggers Ca2+ release from the SR.

PMID- 7818872
TI  - Reflexes and the eye.
AB  - Reflexes are an essential part of protective and homeostatic function, both in
      general terms and with specific reference to ocular structures. A wide range of
      stimuli and responses, with varying degrees of central processing, is involved in
      such reflexes. The simplest reflexes are monosynaptic, such as the stretch or
      myotatic reflex. More complex polysynaptic reflexes are involved in many
      regulatory and protective functions--these include autonomic as well as somatic
      reflexes. Ocular autonomic reflexes include the oculocardiac, pupillary,
      accommodative and lacrimatory reflexes. Ocular somatic reflexes include eyelid
      and extra-ocular muscle reflexes (such as Bell's phenomenon, vestibulo-ocular and
      optokinetic reflexes). An account of the above reflexes is given in the format of
      an essay, modified from the FRACO Part I Examination in Physiology. The topic was
      'Discuss reflex activities with particular reference to the eye'. The content is
      based on several of the texts recommended for the Part I Examination, as listed
      under references.

PMID- 7818873
TI  - The importance of epidemiology in understanding eye disease.
AB  - Most leading causes of visual impairment are age related, so the health care
      implications of an increasing prevalence of eye disease in the elderly are
      significant. Epidemiological research provides the foundation to address
      immediate and long-term needs associated with visual impairment and eye disease.
      It contributes to a community's knowledge of the presence, diagnosis,
      characteristics, and distribution of eye conditions affecting the elderly.
      Obtaining accurate epidemiological information on the extent of visual impairment
      and eye disease in the community is essential to determine and estimate the cost
      of primary and secondary eye health care needs.

PMID- 7818874
TI  - Necrotising anterior scleritis after pterygium surgery.
AB  - Necrotising anterior scleritis is a rare sequela of ocular surgery. Typically an
      intense scleral inflammation develops at or adjacent to the site of the previous
      surgery. Necrosis supervenes and may then progress circumferentially to involve
      much of the anterior sclera. Surgically induced necrotising scleritis (SINS) has
      been previously described after cataract extraction, trabeculectomy, retinal
      detachment and strabismus surgery. We report three cases of SINS following
      pterygium excision. In each case the disease was prolonged, progressive and
      required protracted immunosuppressive therapy.

PMID- 7818875
TI  - Sterile ocular inflammatory reactions to monofilament suture material.
AB  - OBJECTIVE: To report six cases of sterile inflammatory reactions to fine
      monofilament suture materials, which is exceedingly rare in ophthalmology.
      METHODS: We report six patients (four underwent penetrating keratoplasty and two
      underwent cataract surgery) with unusually severe local inflammatory reactions to
      suture material. RESULTS: Patients developed multiple focal inflammatory
      infiltrates and corneal oedema related to 10/0 monofilament nylon sutures. Four
      patients had evidence of either atopy or raised serum IgE and one had an
      autoimmune disorder (systemic lupus erythematosis). Onset was four to 11 days in
      five cases and six weeks in one. Allograft reaction occurred in two of the four
      corneal grafts, and three grafts failed. One of the cataract patients developed
      significant against-the-rule astigmatism. Microbial cultures of corneal
      scrapings, donor corneal rims, and suture material were generally negative.
      Polymorphonuclear leucocytes were noted on Gram stain in four cases, and cytology
      of corneal scrapings demonstrated eosinophils in one case. CONCLUSIONS: Sterile
      inflammatory reactions to monofilament suture material are an uncommon
      complication of ocular surgery which may lead to corneal graft failure, and which
      is more common in atopic individuals. Systemic steroid therapy may be required.

PMID- 7818876
TI  - Age-related medial ectropion of the lower eyelid.
AB  - BACKGROUND: A simplified procedure is proposed for the repair of medial lower
      eyelid age-related ectropion. METHODS: A posterior horizontal incision is made in
      the medial half of the lower eyelid at the inferior border of tarsus. The lower
      eyelid retractors are exposed and then plicated to the tarsus without excision of
      posterior lamellae or the use of everting sutures. The lid is then shortened
      horizontally with excision of a pentagonal section or lateral tarsal strip
      procedure. RESULTS: The procedure was performed in six patients successfully
      without complication. CONCLUSIONS: This is an effective method for repair of
      lower lid medial age-related ectropion.

PMID- 7818877
TI  - Occlusion therapy for strabismic amblyopia.
AB  - OBJECTIVE: To assess the outcome of occlusion therapy in strabismic amblyopia.
      METHODS: The case notes of 369 children requiring strabismus surgery were
      reviewed. RESULTS: Of 369 children requiring surgical correction for strabismus,
      109 had strabismic amblyopia. All of these patients were treated with occlusion.
      Seventy-eight per cent (85 of 109) had improvement of their visual acuity to
      within one Snellen line of the other eye. Another 11% (12 of 109) of patients
      genuinely failed to achieve equal acuity in both eyes despite occlusion and 11%
      (11 of 109) failed to improve due to poor compliance. CONCLUSIONS: Occlusion for
      six hours per day, every day, produced an effective and rapid response in most
      patients. There was no occlusion amblyopia. Admission to hospital for occlusion
      was effective in some refractory cases.

PMID- 7818878
TI  - Community photoscreening of six to nine month old infants for amblyopiogenic risk
      factors.
AB  - Photorefraction (PR) is gaining acceptance as potentially the most effective
      objective screening technique for amblyopia risk factors in the preverbal child.
      This study determined the validity and feasibility of using the Auckland
      eccentric photorefractor in the detection of amblyopiogenic factors in six to
      nine month old infants in an established community-based vision screening
      program. Photographs were analysed and compared to results of clinical
      examination including cycloplegic refraction. Amblyopia risk factors were present
      in 7.2% of the infants clinically examined. Analysis only of readable photographs
      in children who were also clinically examined, gave sensitivities ranging from
      71% to 79%, and specificities ranging from 81% to 86%. Inclusion in the analysis
      of photo-failures lowered sensitivity figures to 56% to 61%, and specificity to
      63% to 70%. Photofailures were predominantly due to poor operator technique.
      Calculation of kappa scores indicated fair observer reliability. In conclusion,
      PR could provide a feasible and sufficiently reliable screening technique in the
      infant, but requires adequate training and auditing of screening personnel
      performance for optimum effectiveness.

PMID- 7818879
TI  - Adult Coats' disease in branch retinal vein occlusion.
AB  - We report a case of adult Coats disease secondary to a branch retinal vein
      occlusion. Angiograms show the relationship of the peripheral telangiectasis,
      aneurysm formation and vascular incompetence to the peripheral retinal ischaemia.
      The possible role of vascular remodelling in the pathogenesis of this uncommon
      complication of a common condition is discussed.

PMID- 7818880
TI  - Scedosporium prolificans sclerokeratitis.
AB  - BACKGROUND: The fungus Scedosporium prolificans was first described as a human
      pathogen in 1984, and has been associated with metastatic endophthalmitis and one
      previously reported case of sclerokeratitis. METHODS: We report a case of S.
      prolificans sclerokeratitis in the setting of late scleral necrosis complicating
      pterygium surgery with adjunctive beta-irradiation. RESULTS: A poor clinical
      response to topical natamycin and amphotericin B, and systemic itraconazole and
      ketoconazole was encountered. Enucleation was required, with subsequent
      microbiological cure. Pathological correlation is described. CONCLUSIONS: S.
      prolificans infections often respond poorly to medical therapy. Early surgical
      intervention is indicated in culture-proven scleritis due to Scedosporium
      prolificans.

PMID- 7818881
TI  - Removable sutures in glaucoma surgery.

PMID- 7818882
TI  - Choroidal folds in Graves' ophthalmopathy.

PMID- 7818883
TI  - Surgically induced astigmatism.

PMID- 7818884
TI  - Autologous blood facilitation of lid laser treatment.

PMID- 7818885
TI  - A method for in vitro DNase I footprinting analysis on supercoiled templates.

PMID- 7818886
TI  - Hints for direct sequencing of PCR-generated single-stranded DNA.

PMID- 7818887
TI  - Easy-read DNA sequencing gels.

PMID- 7818888
TI  - Transporting and storing field-collected specimens for DNA without refrigeration
      for subsequent DNA extraction and analysis.

PMID- 7818889
TI  - Extraction of DNA from fish blood and sperm.

PMID- 7818890
TI  - DNA preparations from Aspergillus and other filamentous fungi.

PMID- 7818891
TI  - Plasmid DNA isolation utilizing a novel nonionic detergent.

PMID- 7818892
TI  - Repeated PCR of a gel band can be used to obtain a single PCR band.

PMID- 7818893
TI  - Hemi-nested quantitative competitive PCR of HIV-1.

PMID- 7818894
TI  - Rapid cDNA cloning by PCR screening.

PMID- 7818895
TI  - An efficient procedure for obtaining long cDNA clones from phage library
      screening.

PMID- 7818896
TI  - A method for construction of bacterial hosts for lac-based cloning and expression
      vectors: alpha-complementation and regulated expression.

PMID- 7818897
TI  - Creation of a rare cutter multiple cloning site.

PMID- 7818898
TI  - Rapid allelotype analysis of p53 knockout mice.

PMID- 7818899
TI  - Nonradioactive, solid-phase DNase I footprints analyzed on an A.L.F. DNA
      Sequencer.
AB  - Solid-phase DNase I footprinting provides a powerful tool for analyzing the
      sequence-specific interactions of DNA binding proteins. Classically this type of
      assay requires radioactively labeled DNA molecules. Substitution of the isotope
      by fluorescein labeling of the DNA fragments enables the analysis of footprint
      patterns on a standard automated laser fluorescent (A.L.F.) DNA Sequencer. The
      combination of solid-phase footprinting technology and fluorescence-based
      nonradioactive detection of fragments has unique advantages over established
      footprinting technologies.

PMID- 7818900
TI  - Improved accuracy in direct automated DNA sequencing of small PCR products by
      optimizing the template concentration.
AB  - Data are presented illustrating the optimum concentration range of reverse
      transcription PCR-generated products under 500 bp for accurate base calling with
      direct automated DNA sequencing. A 357-bp fragment of the human estrogen
      receptor, which includes the DNA binding domain of the protein, was used as a
      representative example of a gene fragment that can be rapidly amplified and
      sequenced. Using the Taq DNA polymerase dye terminator sequencing protocol and
      automated sequencing apparatus from Applied BioSystems, 0.1 to 1.0 pmol of PCR
      product in a 20-microL reaction volume provided > 97% accurate base detection.
      Concentrations greater or lower than this range increased the number of ambiguous
      bases due to alterations in the signal-to-noise ratios. This procedure has been
      successfully utilized with 140-440-bp PCR products within the optimum
      concentration range. These results show that low amounts of PCR products are
      necessary and sufficient for direct sequence analysis.

PMID- 7818901
TI  - Application of cycle dideoxy fingerprinting to screening heterogeneous
      populations of the equine infectious anemia virus.
AB  - Nucleotide sequence heterogeneity in a population of the equine infectious anemia
      virus (EIAV) was investigated using a modification of the dideoxy fingerprinting
      (ddF) technique. PCR-amplified regions of the gag gene from EIAV isolates were
      ligated into plasmid vectors and used to transform bacteria. The single
      dideoxynucleotide sequencing step was performed using plasmid DNA prepared from
      individual bacterial colonies using an 35S end-labeled primer and Taq DNA
      polymerase. Analysis of the products of this reaction was conducted using non
      denaturing polyacrylamide gel electrophoresis. Polymorphism within this gene was
      suggested by the presence of several distinct electrophoretic profiles.
      Significantly, each profile could be correlated with variations in nucleotide
      sequence, which demonstrates that cycle ddF (CddF) offers a rapid and sensitive
      approach to identify polymorphism in PCR-amplified products.

PMID- 7818902
TI  - Comparative sensitivity of alternative single-strand conformation polymorphism
      (SSCP) methods.
AB  - Single-strand conformation polymorphism (SSCP) analysis is a genetic screening
      technique that allows for the rapid detection of single nucleotide substitutions
      in fragments of PCR-amplified genomic DNA or cDNA. Several alternative protocols
      are now being commonly used to resolve differences in electrophoretic mobility of
      single-stranded DNA fragments. The aim of this study was to directly compare the
      sensitivity of three popular SSCP methods using a panel of 19 known human
      mutations/polymorphisms present in genomic DNA samples. Using a single
      electrophoresis protocol, 95% of the mutations were detected using small-format
      PhastGel and the PhastSystem. Large-format gels (5% polyacrylamide and Hydrolink
      MDE) were tested both with and without the addition of 10% glycerol. The
      sensitivity for polyacrylamide and Hydrolink-MDE gels without glycerol was 89%
      and 79%, respectively, and 68% or 63%, respectively, for glycerol-containing
      gels. However, all mutations were detected with either polyacrylamide or
      Hydrolink-MDE when both glycerol and non-glycerol gels were examined. We conclude
      that comparable very high detection efficiency can be achieved using the
      PhastSystem or by using a combination of two large-gel conditions with either
      polyacrylamide or Hydrolink-MDE.

PMID- 7818903
TI  - Large-scale screening of yeast artificial chromosome libraries using PCR.
AB  - The construction of physical maps of the human genome using sequence-tagged site
      content mapping requires that thousands of PCR amplifications be performed. On
      this scale, measures to reduce cost and to increase throughput become serious
      considerations. We describe relatively simple measures developed in our
      laboratory that increase the rate at which these reactions can be performed in a
      cost-effective manner. These measures have been extensively tested in our
      laboratory and are readily applicable in other laboratories including those
      performing library screening on a more modest scale.

PMID- 7818904
TI  - Quantitation of two histochemical markers in the same extract using
      chemiluminescent substrates.
AB  - Factors that influence early events of primary tumor development have been
      cumbersome to evaluate because of the need to either wait for tumor palpability
      after experimental manipulation or use of radiolabel to evaluate cell clearance.
      To facilitate these and similar analyses of cells in vivo, new methods are
      described that utilize histochemical marker genes to quantitate tumor cell number
      in a target tissue through the use of luminescent, enzymatic assays for these
      gene products. 3T3 Cells transfected with either human placental alkaline
      phosphatase or bacterial lacZ genes were injected subcutaneously into athymic
      nude mice. Using luminescent substrates designed for marker gene enzymes,
      extracts from homogenized tumor cell-bearing skins were assayed for the
      corresponding marker enzyme activities, which were optimized for recovery from
      skin extracts and correlated to cell number. The homogenization buffer used for
      these assays was designed to accommodate the optimal and simultaneous recovery of
      cytosolic beta-galactosidase and membrane-linked alkaline phosphatase from the
      skin, as well as from cultured cells. These assays provide an inexpensive,
      sensitive method for quantitatively monitoring the fate of cells genetically
      tagged with marker genes in various in vivo environments.

PMID- 7818905
TI  - Ligand binding assays with recombinant proteins refolded on an affinity matrix.
AB  - This paper describes a procedure for performing ligand binding assays with
      recombinant proteins or protein fragments that can bind to an affinity matrix in
      the presence or absence of a denaturing agent but which require the presence of
      the denaturing agent to remain in solution. The method involves coupling of a
      known amount of the protein in a denaturing medium to a known amount of the
      affinity matrix, replacing the denaturing agent with a physiological buffer, and
      finally using the suspension of this protein-coupled matrix as the source of the
      recombinant protein to be studied for its functional properties. A constant
      volume of this suspension is incubated with different concentrations of a
      radiolabeled ligand. Radioactivity bound to the protein-coupled affinity matrix
      is determined after centrifugation and washing of the pellet. Nonspecific binding
      is determined either by using the uncoupled affinity matrix or by the standard
      technique of measuring the binding in the presence of excess unlabeled ligand.

PMID- 7818906
TI  - A microchip for quantitative detection of molecules utilizing luminescent and
      radioisotope reporter groups.
AB  - Through the marriage of microelectronics and molecular biology, a miniaturized
      device is presented for ultrasensitive detection of labeled molecules. The
      novelty of the approach is the direct integration of a charge-coupled device
      (CCD) and a probe-based assay. Specifically, a CCD detector serves as an active
      solid support that quantitatively detects and images the distribution of labeled
      target molecules near the spatially addressable pixels. The device exploits the
      inherent characteristics of microelectronics that accommodate highly parallel
      assays, ultrasensitive detection, high throughput, integrated data acquisition
      and computation. Hence, the technology presented offers substantial practical
      utility to both research and clinical diagnostic applications that require
      quantitative analysis of bound molecules. Specifically for probe-based assays
      such as reverse dot blots, hybridization of radiolabeled or fluorescently
      labeled, target DNA can be quantitatively assessed within seconds due to the high
      sensitivity and direct coupling employed.

PMID- 7818907
TI  - A survey of nucleic acid services in core laboratories.
AB  - Core facility services related to DNA synthesis and sequencing were surveyed by
      the Association of Biomolecular Resource Facilities. Responses from 85 facilities
      offering DNA synthesis and 37 facilities offering DNA sequencing were obtained.
      Data on instrumentation, volume, number of users, cost, methodology and a number
      of other criteria were obtained. The volume of work performed by these
      centralized core facilities was quite substantial (combined synthesis output of 4
      million bases per year and a combined sequencing output of 35 million bases per
      year). The large number of users supported by these facilities and the high
      sample throughput make these core resource facilities good indicators of
      technological trends.

PMID- 7818908
TI  - Nucleotide sequencing double-stranded plasmids with primers selected from a
      nonamer library.
AB  - Nonamer primers, selected from a nonamer library, were tested by sequencing two
      plasmid subclones containing known insert sequences. These sequences were scanned
      (nonamer-mapped) against the 2391-member nonamer library to identify all members
      that share a 100% match at only one site. A total of 59 nonamers were tested
      using a slightly modified T7 polymerase sequencing procedure for double-stranded
      DNA. The success rate for nonamer primed reactions was about 60%, and single
      stranded coverage was obtained for approximately 90% of each plasmid insert. The
      results presented demonstrate that a nonamer library, with as few as 2391
      members, can greatly aid the completion of many sequencing projects by reducing
      the number of required custom primers. With the development of a technique for
      the rapid identification of all useful library primers for a particular
      sequencing project, one could envision a high-throughput shotgun-type sequencing
      procedure that would not require large numbers of subclones.

PMID- 7818909
TI  - PCR-based DNA typing of saliva on stamps and envelopes.
AB  - In forensic cases involving mail bombs, extortion, kidnapping or threatening
      letters, biological evidence such as the saliva used to attach the stamp and seal
      the envelope could be used for genetic analysis. We have developed a highly
      sensitive semi-nested PCR method for the HLA-DRB1 locus; suitable for the
      analyses of very limited amounts of DNA. When applied to a set of stamps and
      envelopes with saliva from control individuals, typing results were consistent
      with those obtained using hairs drawn from the same individuals. No interference
      was found due to DNA from the fingerprints of people handling the letters. The
      system was applied to three forensic cases with threatening letters. The first
      case resulted in an exclusion of the suspect. In the second case, the suspect
      could not be excluded (probability of identical genotype by chance > 0.01). These
      results demonstrate that biological evidence in cases with threatening letters is
      amenable to genetic typing.

PMID- 7818910
TI  - DNA sequencing: modular primers for automated walking.
AB  - Here we describe our progress in the development of the technology of DNA
      sequencing by primer walking based on the modular primer approach, which
      eliminates the primer synthesis bottleneck. Modular primers are assembled from 5
      mers, 6-mers, or 7-mers selected from a presynthesized library of as few as 1000
      oligonucleotides. This technology is expected to reduce the time per walk by a
      factor of 20 to 50, and the cost of DNA sequencing by a factor of 5 to 15. Both
      time and expense will be saved not only on the primer synthesis per se but, more
      importantly, as a result of the closed-end automation of the complete cycle of
      walking sequencing, where no human intervention will be required between the
      walks. Such closed-end automation has until now been precluded due to the need to
      synthesize a new primer for each walk. As a part of the closed cycle automation
      development, this report deals with modular primers used for sequencing with
      fluorescent dye terminators. The success rate and the quality of automated
      sequencing with modular primers are found similar to those with the conventional
      17-20-base-long primers. One of the advantages of the described technique is
      simple purification without any proteins that need to be removed.

PMID- 7818911
TI  - Detection of a point mutation using short oligonucleotide probes in allele
      specific hybridization.
AB  - Two nonradioactive and simple procedures were developed to detect the A985G point
      mutation that causes medium-chain acyl-CoA deficiency. In both of these assays,
      short oligonucleotide probes were used in allele-specific hybridization combined
      with DNA amplification. The lower limit for a useful probe was found to be
      between 9 and 12 base pairs. Time-resolved fluorometry was utilized as the label
      technology and microtitration plates as the solid support. In one of the assay
      formats, probes labeled with europium and samarium chelates were used to
      simultaneously detect the mutant and normal alleles from the same hybridization
      reaction. In addition, the discrimination efficiency of different probes was
      characterized by cross-reactivity determinations and by measuring affinities of
      the probes towards fully complementary as well as towards mismatch-forming target
      oligonucleotides. All of the 80 coded patient samples analyzed were correctly
      typed in both of the assay formats used.

PMID- 7818912
TI  - Automated DNA sequencing using 4-color fluorescent detection of reactions primed
      with hexamer strings.
AB  - The use of strings of contiguous short primers rather than a single long primer
      has the potential to greatly diminish the cost, time and management efforts
      associated with sequencing by primer walking. For maximum impact, this chemistry
      must be adaptable to current fluorescent automated sequencers, which, while
      allowing automated acquisition of data, have reduced sensitivity when compared
      with radioactive-based sequencing. The ability to use hexamer strings on Applied
      Biosystems DNA sequencers has now been demonstrated for single-stranded
      templates. Procedures are described that allow sequence to be obtained up to 400
      bases from the priming site. Signal strength is sufficient in this region to
      allow single base resolution and highly accurate automatic base calling to be
      performed by the sequencer. While these conditions can no doubt be further
      optimized, these results show the feasibility of inexpensive primer walking using
      hexamer string primers on currently available commercial DNA sequencers. This
      should have a wide range of applications from genome sequencing projects to the
      sequencing of cDNA clones without the necessity of creating nested deletions or
      the necessity of spending inordinate amounts of time and money on oligonucleotide
      synthesis.

PMID- 7818913
TI  - ScreenMax plasmid mini-prep: super rapid plasmid DNA extraction method.
AB  - An ultra-quick method for plasmid DNA extraction using the ScreenMax Plasmid Mini
      prep Kit was optimized. Since the method has fewer steps than current methods,
      the entire process takes only 12 min for two sets of plasmid DNA extractions. DNA
      quality was excellent for further analyses, including DNA sequencing. The kit's
      new medium, MMB, provided 5 times the viable cell count and 7 times the dry cell
      weight compared with the conventional LB medium. The yield of plasmid DNA was 5
      times better than from LB medium. From 200 microL of culture, the maximum yield
      was 7.5 micrograms. The ScreenMax Plasmid Mini-Prep is not only simple and
      economical but also safe because of its mild reagents. This new procedure is both
      reliable and reproducible.

PMID- 7818914
TI  - A new protease activity assay using fluorescence polarization.
AB  - Fluorescence polarization (FP) technology was used to develop an assay for
      protease activity that is more sensitive than other nonradioactive protease
      assays and requires no separations, precipitations or transfers of the reaction
      mixture. FP measures changes in the molecular volume of fluorescently labeled
      molecules. In the assay described in the present studies, changes in molecular
      volume due to the cleavage of intact fluorescein thiocarbamoyl (FTC)-casein
      molecules to smaller FTC peptides were measured. The sensitivity of the FP
      protease assay was compared with a non-FP fluorescent assay. The FP-based assay
      was twofold to twentyfold more sensitive than the non-FP assay, depending on the
      protease tested. Because measurements were taken in real time, the progress of
      the reaction was followed both kinetically and at a single time point. This assay
      provided a sensitive measure of activity for the three common protease classes:
      serine proteases, sulfhydryl proteases and acid proteases.

PMID- 7818915
TI  - Descriptive epidemiology of cancer around the Baltic Sea.
AB  - Baltic Sea countries--Denmark, Estonia, Finland, Germany, Latvia, Lithuania,
      Poland, the Russian Federation and Sweden--have expressed deep interest in
      developing collaborative research projects chiefly in descriptive epidemiology of
      cancer. In order to assess potentials for joint studies, an attempt was
      undertaken to characterize cancer registration, cancer incidence patterns,
      temporal trends in cancer mortality and research productivity between these
      countries. Standards of cancer registration are highest in the Nordic countries
      (Denmark, Finland, Sweden). These countries and Germany are also doing more
      productive research. Great differences in incidence and in mortality trends
      around the Baltic Sea offer promising opportunities for epidemiologic studies.
      Scarcity of well-trained professional epidemiologists and other resources in
      Latvia, Lithuania, Estonia and the Russian Federation is the main factor limiting
      the planning of joint large-scale epidemiologic studies of cancer.

PMID- 7818916
TI  - Protease inhibitors in chemoprevention of cancer. An overview.
AB  - In the search for chemopreventive agents for cancer many natural products have
      been identified. Among them extensive experimental studies have been made on
      protease inhibitors which not only occur naturally in many plant products, but
      have also been synthesized in the laboratory. Many of these studies revealed the
      fact that protease inhibitors are able to prevent carcinogenesis and tumour
      promotion. A review of the reports available to date suggests that protease
      inhibitors are potential chemopreventive agents although their biological role
      and mechanism of action are not very clear.

PMID- 7818917
TI  - Epstein-Barr virus infection, salted fish and nasopharyngeal carcinoma. A case
      control study in southern China.
AB  - Two hundred and five histologically confirmed cases of nasopharyngeal carcinoma
      (NPC) in southern China, and an equal number of matched controls, were
      investigated for their dietary habits, occupational exposure, use of tobacco and
      alcohol, history of relatives with NPC, and IgA against Epstein-Barr virus (EBV)
      capsid antigen (IgA/VCA). Positive IgA/VCA and intake of salted fish were
      associated with a strong excess risk of NPC. The association persisted after
      adjustment for other factors. The combination of salted fish and EBV was strongly
      associated with NPC, and more so than EBV or salted fish per se. Multivariate
      analyses showed that IgA/VCA was the most important predictor of NPC, and salted
      fish the second most important. These results suggest that EBV has a strong
      effect on the development of NPC. The exclusion of EBV and genetic factors in
      earlier epidemiological studies may have resulted in an overestimation of salted
      fish as important etiological factor causing NPC.

PMID- 7818918
TI  - Prognostic studies in breast cancer. Multivariate combination of nodal status,
      proliferation index, tumor size, and DNA ploidy.
AB  - We studied histological samples and clinical data from 111 breast carcinoma
      patients originally treated in 1975-1977 who did not have distant metastases at
      the time of diagnosis. A multivariate survival analysis using the Cox model
      selected the studied variables in the following order according to their
      prognostic association (breast cancer deaths, or deaths from any cause): axillary
      lymph node status, tumor size, mitotic index, and DNA ploidy status. The
      association of the different variables to the prognosis in respect to breast
      cancer deaths was evaluated 1-10 years after treatment by stepwise logistic
      regression. Lymph node status, tumor size, mitotic index, and DNA ploidy all
      showed significant relation to the prognosis but this association varied
      considerably with time of observation.

PMID- 7818919
TI  - Development of a European Organization for Research and Treatment of Cancer
      (EORTC) questionnaire module to be used in quality of life assessments in head
      and neck cancer patients. EORTC Quality of Life Study Group.
AB  - A head and neck cancer specific questionnaire module designed to be used in
      quality of life assessments before, during, and after radiotherapy and surgery,
      with or without combinations with chemotherapy has been developed in accordance
      with guidelines given by the EORTC Quality of Life Study Group. Relevant issues
      were generated by means of literature search, and interviews with specialists and
      patients. Pre-testing of a preliminary questionnaire module was performed in
      patients from Norway, Sweden, Denmark, United Kingdom and French-speaking
      Belgium. The resulting head and neck cancer module, the EORTC QLQ-H&N37, includes
      37 items concerning disease and treatment related symptoms, social function and
      sexuality. By using a combination of the general EORTC QLQ-C30 and the EORTC QLQ
      H&N37, health-related quality of life measurements may be compared between
      studies in different cancer populations, and still be sensitive to changes in the
      target population.

PMID- 7818920
TI  - Coping, psychosocial well-being and anxiety in cancer patients at follow-up
      visits.
AB  - Coping, psychosocial well-being, situation-specific anxiety and cancer-related
      worry were assessed in 197 consecutive cancer patients attending follow-up
      visits. Participants completed questionnaire on three occasions: at the follow-up
      visit, some days later (n = 175) and three weeks later (n = 125). High levels of
      coping styles 'Anxious Preoccupation' and 'Helplessness/Hopelessness' were
      associated with low levels of psychosocial well-being, more situation-specific
      anxiety and more cancer-related worry. High levels of 'Fighting Spirit' and
      'Fatalistic' were found to be associated with high psychosocial well-being and,
      for 'Fighting Spirit', also with less cancer-related worry. Patients with a
      'dismal' prognosis were found to have higher levels of
      'Helplessness/Hopelessness' than patients with a more 'favorable' prognosis.
      Clinical implications of these findings are discussed.

PMID- 7818921
TI  - Management options for primary hepatocellular carcinoma. An overview.
AB  - Hepatocellular carcinoma (HCC) is the seventh most common cancer in men and the
      ninth most common cancer in women with 500,000 to 1,000,000 new cases per year.
      Several risk factors (sex hormones, alcohol, thorotrast, aflatoxin B1, hepatitis
      B or C, haemochromatosis, alpha 1-antitrypsin deficiency, tyrosinemia, porphyria
      cutanea tarda, acute intermittent porphyria, Wilson's disease) associated with
      the development of HCC have been identified from epidemiological studies. The
      diagnosis is usually based on a combination of clinical and laboratory findings
      together with radiographic and histopathologic characteristics. HCC remains
      difficult to treat with a median survival of 3 to 6 months after the onset of
      symptoms. Surgical resection is the mainstay of treatment for HCC. Transcatheter
      arterial embolization and percutaneous ethanol injection have been used but
      neither therapy has been evaluated in a prospective randomized study. Combination
      treatment (e.g. chemotherapy and resection) may be of value but randomized
      controlled trials with long-term follow-up are still needed. Liver
      transplantation should be reserved for carefully selected patients.

PMID- 7818922
TI  - Serum c-erbB-2 in breast cancer patients.
AB  - The c-erbB-2 oncogene product in serum (serum c-erbB-2) was measured by an enzyme
      immunoassay kit. The 12 U/ml cut-off level was estimated as the mean plus two
      standard deviations for 250 healthy women. With this cut-off level increased
      serum c-erbB-2 was found in 12.0% of primary breast cancer cases (n = 25), in
      4.9% of non-recurrent breast cancer patients (n = 82), and in 31.4% of patients
      with recurrent breast cancer (n = 35). In patients with primary and recurrent
      breast cancer, whose sera were assayed concurrently for serum c-erbB-2, CEA and
      CA15-3, the positive rates of these markers were fairly similar. However, their
      combined use significantly increased the sensitivity as compared to the use of
      any one marker alone.

PMID- 7818923
TI  - Thyroid autoantibodies and thyroid function in patients with gastric cancer.
AB  - Antibodies against thyroid antigens are commonly found in patients with chronic
      gastritis type B (20-30%) and pernicious anaemia (50%), two disorders that
      predispose to gastric cancer. In addition, thyroid disease in increased incidence
      has been reported in breast and in colon cancer. In order to determine a) the
      incidence of antithyroid antibodies (ATA) in gastric cancer, b) the thyroid
      function in patients with ATA and c) the correlation between ATA and the presence
      of chronic gastritis, we examined the sera of 32 patients with gastric cancer
      (GC) for the presence of antithyroglobulin and antimicrosomal antibodies. T3, T4
      and TSH values were also measured. The sera of 36 patients with malignant tumours
      of the GI tract other than stomach (OMT) and of 40 healthy blood donors were used
      as controls. Three of the 32 GC patients had antithyroglobulin antibodies, 4 had
      antimicrosomal and one had both types. Of the eight patients with ATA (25%) only
      two had hypothyroidism and another two histologically diagnosed chronic
      gastritis. Three sera of the healthy controls and one of the OMT had also
      antithyroid antibodies. To conclude, a significant number of patients with GC had
      ATA as compared to controls (p < 0.01) but the presence of ATA did not
      necessarily indicate an abnormality of thyroid function. The presence of
      antibodies did not correlate with chronic gastritis type B.

PMID- 7818924
TI  - The value of bone marrow examination in small cell carcinoma of the lung.
AB  - Of 668 consecutive patients with SCLC, 472 underwent bone marrow examination for
      staging. In 330 patients a triple examination (sternal aspiration, iliac crest
      aspiration and biopsy) was performed, otherwise a single procedure. Bone marrow
      infiltration (MI) was found in 37% of the patients with extensive disease, and
      the frequencies of a positive finding in single and triple examination were not
      statistically different. In the group having triple examination performed iliac
      crest aspiration alone disclosed MI in 32%. When all three procedures were
      included still more patients with MI were found (42%) but the two values were not
      significantly different. In 6.6% of patients who would have been classified as
      'limited' did bone marrow examination change the stage to extensive disease.
      Based on these results we recommend iliac crest aspiration, but not triple
      examination with iliac crest biopsy, in the staging of SCLC.

PMID- 7818925
TI  - Factors influencing survival of patients after radical surgery for gastric
      cancer. A regional study of 406 patients over a 10-year period.
AB  - The present retrospective report presents a review of prognostic factors
      influencing the survival of 406 gastric cancer patients radically operated on in
      the Tartu Oncology Hospital, Estonia in 1978-1987. All patients underwent total
      (n = 170) or subtotal (n = 236) gastrectomies with extensive lymphadenectomy (260
      R2- and 146 R3-resections) according to the General Rules for the Gastric Cancer
      Study in Surgery and Pathology established by the Japanese Research Society for
      Gastric Cancer, introduced in our hospital at the end of the 1970s and now used
      as the unavoidable procedure for curative gastric cancer surgery. The 30-day
      postoperative mortality was 5.9% and the overall 5-year survival 46.1%. The
      male:female ratio was 0.95 and the mean age 62.4 years. Only 7.6% of all our
      patients operated on had early gastric cancer with a 5-year survival of 80.7%
      whereas 76.8% had T3-T4 tumours with a 5-year survival of 41.0%. Lymph node
      involvement was found in 44.6% of the patients. Independent favourable prognostic
      factors were (the 5-year survivals are presented within parentheses): limited (N0
      N1) lymph node involvement (56.4 vs. 22.6%), pT 1-2 stage (62.8 vs. 41.0%),
      papillary, tubular or poorly differentiated histological pattern (51.9 vs.
      33.1%), subtotal gastrectomy (55.9 vs. 32.4%) and age below 70 years (51.9 vs.
      35.2%). Sex of patients, Borrmann type, size and site of tumour were not
      statistically associated with prognosis at multivariate analysis. Our results
      also suggested that besides predetermined prognostic factors, the surgical policy
      had a great impact on the prognosis of gastric cancer patients. We conclude that
      gastrectomy with combined resections of neighbouring organs directly invaded and
      with extensive lymphadenectomy at least up to the second node group might be the
      procedure of choice for advanced gastric cancer.

PMID- 7818926
TI  - Carboplatin and etoposide in extensive small cell lung cancer.
AB  - The combination of carboplatin and etoposide was evaluated in 61 previously
      untreated patients with extensive small cell lung cancer. Treatment was given at
      four-week intervals with 450 mg/m2 of carboplatin intravenously (i.v.) on day 1
      and etoposide 100 mg/m2 i.v. on days 1-3. The response was complete in 5 (9%) and
      partial in 28 (50%) of the 56 evaluable patients (overall response rate 59%). The
      median time to progression after response as well as the median survival time in
      all evaluable patients was 4.6 months. WHO grade 3 and 4 leukopenia and
      thrombocytopenia occurred in 8% and 11% of the courses respectively. Two
      treatment-related deaths were registered. The combination of carboplatin and
      etoposide used in the present study produced acceptable response rate and
      toxicity, but duration of response and median survival were shorter than expected
      from earlier studies.

PMID- 7818927
TI  - Metastatic or locally advanced colorectal cancer treated with 5-fluorouracil and
      low dose leucovorin.
AB  - Eighty-one patients with metastatic or locally advanced colorectal cancer were
      treated at four oncological centers in Denmark with a regimen consisting of 5
      fluorouracil 400 mg/m2 and leucovorin 20 mg/m2 for 5 consecutive days every 4
      weeks. The response rate was 21% among all 81 patients (CR 3, PR 14). The median
      survival was 10 months regardless of measurability, sex and location of disease.
      Toxicity was mild, 6 (7%) patients were excluded from the study due to
      gastrointestinal side-effects and 15 (19%) patients had the 5-FU dose reduced due
      to side-effects. The results are comparable to those of other studies using
      different doses of leucovorin.

PMID- 7818928
TI  - CHOP chemotherapy of intermediate and high-grade non-Hodgkin's lymphoma.
AB  - The results of CHOP treatment in 63 patients with intermediate and high-grade non
      Hodgkin's lymphoma (Working Formulation D to I), Ann Arbor stage I to IV were
      analyzed. The response rate was 87%, 71% complete remission and 16% partial
      remission with a mean duration of 22 months. The 5-year actuarial survival was
      61% (95% confidence interval, 51-70%). The treatment was well tolerated and no
      deaths due to acute toxicity were observed. Poor prognostic factors in univariate
      analysis were: high-grade histology, stages III and IV, B symptoms, > or = 4
      affected lymph node regions, Karnofsky index < or = 70, erythrocyte sedimentation
      rate (ESR) > 60 mm, haemoglobin < 100 g/l and elevated lactic dehydrogenase
      (LDH). Poor prognostic factors in multivariate analysis were: high-grade
      histology, stages III and IV, haemoglobin < 100 g/l and elevated LDH. In summary,
      good results were obtained with CHOP chemotherapy, without severe toxicity.

PMID- 7818929
TI  - Results of radiotherapy in craniopharyngiomas analysed by the linear quadratic
      model.
AB  - In 23 craniopharyngioma patients treated by limited surgery and external
      radiotherapy, the results concerning local control were analysed by linear
      quadratic formula. A biologically effective dose (BED) of 55 Gy, calculated with
      time factor and an alpha/beta value of 10 Gy, seemed to be adequate for local
      control.

PMID- 7818930
TI  - Recent developments in the radiobiology of cellular membranes.
AB  - We have reviewed the literature on cellular membrane radiobiology over the last
      ten years and, in particular, report on the development of rapid techniques used
      to identify damage soon after irradiation. It is clear that damage can now be
      quantified after low doses, and further refinements can be expected. From the
      work summarised, it would appear that changes to membranes at low doses may occur
      soon after damage to other important macromolecules by intercommunicating
      processes. We believe that there now exists a variety of rapid methods of
      measuring deposition of damage in vital macromolecules, such as cellular
      membranes and DNA, which can give a fuller picture of the overall effects of
      radiation and lead to predictions of eventual cellular mortality.

PMID- 7818931
TI  - Antileukemic activity studies and cellular pharmacology of the analogues of 2
      hydroxy-1H-isoindole-1,3-dione (HISD) alone and in combination with cytosine
      arabinoside (ara-C) against human leukemia cells CEM/0.
AB  - The 2-hydroxy-1H-isoindole-1,3-dione (HISD) derivatives are inhibitors of
      ribonucleotide reductase (RR). Among the seven new compounds of the PL series,
      three were found to be active in cell lines sensitive (CEM/0) or resistant to ara
      C (CEM/ara-C/7A; CEM/dCk[-]. The compounds PL4, PL7 and PL8 exhibited IC50 values
      in micromolar range against the three CEM cell lines. The 3 compounds showed 100-
      to 1000-fold higher cytotoxicity compared to HU against all three CEM cell lines.
      Combination of each of the three active PL compounds with ara-C showed high
      degree of synergism in comparison to the combinations of HU with ara-C against
      both CEM/0 and CEM/ara-C/7A cell lines. The DNA synthetic capacity of CEM/0 cells
      treated with 10 microM PL4 for 24 or 48 h was inhibited > or = 99.8%
      simultaneously the cellular NTP pools were severely depleted. Treatment of CEM/0
      cells with 10 microM PL4 showed steady depletion in all the dNTP pools at 1 or 2
      h and complete depletion by 4 h. The enzyme activity did not recover up to 48 h
      in presence of the drug suggesting irreversible inhibition of RR.

PMID- 7818932
TI  - The influence of selenium, vitamin E, and oestrogen on the development of tumours
      in mice exposed to 90Sr.
AB  - The primary object of this experiment was to evaluate the potential role of the
      antioxidants, selenium and vitamin E, in the anti-tumour defence of mice
      internally irradiated with 90Sr. Comparison in terms of neoplastic response was
      made between mice kept on a selenium and vitamin E deficient diet and mice given
      the same deficient diet but administered selenium and/or vitamin E in a
      controlled manner. The influence of simultaneous oestrogen treatment, known to
      promote radiogenic osteosarcoma induction, was also investigated. Non-irradiated
      mice were used as controls. Results are presented as crude and actuarial tumour
      incidence. No significant difference in tumour yield or actuarial tumour
      incidence was found when the differently treated mouse groups were compared, and
      accordingly no support was gained for the theory that the antioxidants selenium
      and vitamin E constitute a critical part of the complex defence system against
      neoplasms.

PMID- 7818933
TI  - Pharmacokinetics and tolerance of nicotinamide combined with radiation therapy in
      patients with glioblastoma multiforme.
AB  - The pharmacokinetic properties of nicotinamide and its tolerance were studied in
      seven patients affected by glioblastoma multiforme and treated with two fractions
      per day of radiation therapy. Nicotinamide was given orally at two daily doses of
      4 g and then 2 g separated by a 6-h-interval. The treatment was well tolerated in
      almost all patients and had no effect on blood pressure, cardiac rhythm or body
      temperature. Pharmacokinetic analysis showed peak plasma levels (Cmax) above 100
      mg/l 45 minutes after the administration of both doses. This was followed by a
      biexponential decay of plasma concentrations with a thermal half life of 9.4h.
      Tumours were irradiated 1 hour after each drug dose to match with drug Cmax in
      plasma, and although it is too early to evaluate the tumour response, the drug
      levels achieved should be sufficient to improve radiation therapy.

PMID- 7818934
TI  - Oncogenous osteomalacia--report of a case.

PMID- 7818935
TI  - Is gastric cancer heterogeneity the clue to HLA-DR associated susceptibility?

PMID- 7818936
TI  - The role of radiotherapy in tympanojugular chemodectomas.

PMID- 7818937
TI  - Myocardial ischaemia: metabolic disorders leading to cell death.
AB  - Experimental studies have demonstrated that reperfusion is associated with a host
      of distinctive pathophysiological derangements, among which the most important
      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 they also develop in patients, although the
      existence of malignant reperfusion arrhythmias in humans remains uncertain. Both
      reperfusion arrhythmias and myocardial stunning can ben considered a
      manifestation of sublethal, reversible cellular injury. Although the pathogenesis
      of reperfusion arrhythmias and stunning has not been conclusively established,
      there is considerable evidence that generation of oxygen radicals and
      perturbations of calcium homeostasis play an important role. Accordingly,
      antioxidants or calcium antagonists have been shown to be beneficial in
      mitigating these manifestations of reperfusion injury. In contrast, the existence
      of a lethal reperfusion-induced injury remains highly controversial. Although
      many studies have reported reduction of infarct size with antioxidants, numerous
      other investigation have failed to reproduce these results. As a consequence,
      intense controversy persists regarding whether oxygen radicals contribute to
      extending cell death upon reperfusion and whether reperfusion in itself causes
      cell death. It is unlikely that such controversy will be resolved any time soon
      and that clinical therapies aimed at reducing reperfusion-induced cell death will
      become available in the near future.

PMID- 7818938
TI  - Myocardial damage during ischaemia and reperfusion.
AB  - Large quantities of oxygen free radicals can be generated on reperfusion of the
      ischemic myocardium. This phenomenon is probably responsible for a specific
      component of cell damage separate from ischemic injury and may blunt the
      beneficial effects of thrombolysis. Anti-free radical interventions may reduce
      the severity of this "reperfusion injury". However, reports of treatment failures
      indicate that reperfusion injury is a complex phenomenon, and suggest that the
      beneficial effects of treatment may be critically dependent on factors that are
      not clearly understood.

PMID- 7818939
TI  - Intervention in ischaemia. Reperfusion syndrome. Rationale for trimetazidine.
AB  - Although early reperfusion of cardiac tissue is now considered to be the only
      intervention capable of restoring the various cellular functions altered by
      ischaemia and preventing progression towards necrosis of myocardial cells,
      reperfusion is frequently accompanied by various manifestations grouped under the
      heading of reperfusion syndrome or reperfusion injury. Functional recovery is
      therefore not immediate, but usually appears after a certain delay following a
      period of contractile dysfunction (myocardial stunning) lasting for several hours
      or even days after the start of reperfusion. Characteristics reperfusion-induced
      arrhythmias are also observed. The cellular mechanisms underlying the reperfusion
      syndrome may involve cellular calcium overload, over-production of oxygen-derived
      free radicals, acidosis and/or development of an inflammatory reaction. Numerous
      pharmacological studies have been conducted over several years designed to limit
      such reperfusion injury and, consequently, prevent stunning and/or reperfusion
      induced arrhythmias. A number of experimental studies in this field have
      demonstrated that trimetazidine exerts direct anti-ischaemic effects, limiting
      calcium accumulation and acidosis, inflammation and oxygen-derived free radical
      production following reperfusion. This agent therefore appears to be particularly
      promising clinically in the treatment of reperfusion lesions, for example in
      combination with thrombolysis during the acute phase of myocardial infarction.

PMID- 7818940
TI  - [Therapeutic application of myocardial cytoprotection].

PMID- 7818942
TI  - [Compliance to therapy -- its importance in research and clinical practice].
AB  - Compliance, defined as patients behaviour to treatment schedule over time,
      specially in chronic diseases, is an important parameter to be measured in
      clinical trials. Compliance to a specific drug may compromise the final efficacy
      expected result assumed by phase I II and III studies. The medication events
      monitors systems (MEMS) appeared to get a more specific and sensitive measurement
      than the classic counting pills and drug or markers levels to analyses of
      compliance. The authors made a revision of literature in order to evaluate the
      benefits of compliance measurement in trials (specially hypertension as a
      paradigm of chronic disease) and clinical practice. Partial compliance with
      antihypertensive treatment could be an obstacle to an effective control or to
      demonstrate long term efficacy on decreasing morbidity and mortality. A short
      discussion is made about the possible benefits of using MEMS on clinical trials
      to evaluate patient's quality of life and behaviour to long term treatment for
      chronic diseases.

PMID- 7818941
TI  - [Hemodynamic effects of propafenone in dogs anesthesized with halothane or
      isoflurane].
AB  - OBJECTIVE: Several studies suggest that anaesthetic drugs influence the
      haemodynamic effects of the antiarrhythmic drugs. The aim of this study was to
      compare the haemodynamic effects of a standard dose of propafenone (1.5 mg/kg) on
      dogs anaesthetized with halothane or with isoflurane. DESIGN: Randomized
      laboratory animal study. MATERIAL AND METHODS: Six dogs were anaesthetized with
      1% of halothane-Group I, and six dogs with an equianaesthetic dosage of
      isoflurane (1.5%)-Group II. Dogs breathed in spontaneous ventilation.
      Haemodynamic monitoring was performed with a femural arterial catheter and a flow
      directed pulmonary artery catheter and cardiac output was measured by
      thermodilution. After a haemodynamic assessment considered as initial a bolus of
      1.5 mg/kg of propafenone was given during a period of 30 seconds and similar
      assessments were made 5, 15, 30 and 60 minutes after. RESULTS: Before
      propafenone, heart rate was significantly higher in Group II-isoflurane (p <
      0.05). After propafenone we found: In both Groups, a decrease in the cardiac
      output (p < 0.05) with the mean arterial pressure maintained; in Group I
      (halothane) a decrease in the stroke volume (p < 0.05) which was not found in
      Group II (p = ns); In Group II (isoflurane) a decrease in heart rate (p < 0.05)
      not found in Group I (p = ns). All the changes were higher at the 5th minute
      values. 30th minute and 60th minute values were not significantly different from
      initial values. CONCLUSION: In dogs anaesthetized with halothane 1.2 MAC a
      reduction in the stroke volume, resulting in a cardiac output decrease, was
      observed, suggesting that propafenone increases the negative inotropic action of
      halothane. In dogs anaesthetized with isoflurane 1.2 MAC the decrease in cardiac
      output was similar to the decrease in heart rate, and therefore no reduction in
      the stroke volume was observed. The decrease in the heart rate found in this
      group but not in the halothane group was probably related with the beta-blocker
      action of the propafenone. Looking to the systemic vascular resistances, our
      study suggested that propafenone didn't have any vasodilator effect during
      halogenated anaesthesia.

PMID- 7818943
TI  - [Adrenal gland adenoma sensitive to renin].
AB  - Aldosterone-producing adenomas responsive to renin are an extremely rare subgroup
      of primary hyperaldosteronism and raise some diagnostic problems. In reference to
      the presentation of one case, some theoretical considerations regarding diagnosis
      are made.

PMID- 7818944
TI  - [Multiplanar transesophageal echocardiography: technique, methodology, and
      applications].
AB  - OBJECTIVE: To present the experience of transesophageal echocardiography with a
      multiplane probe, its methodology, the advantages, disadvantages and diagnostic
      improvements of this type of probe. SETTING: Laboratory of Echocardiography of
      the General Hospital Gregorio Maranon. MATERIAL AND METHODS: Analysis of the
      first 1000 examinations performed on hospitalized patients and outpatients, in
      most cases to study either native valvular heart disease and valvular prosthesis
      or to search for embolic sources. We evaluate the advantages, disadvantages,
      initial difficulties and complications of this type of probe. RESULTS: Multiplane
      probe provides continuous imaging from 0 degree to 180 degrees without need of
      intraesophagic movements. This type of probe increases the diagnostic capability
      of transesophagic echocardiography because it performs as a scanning of anatomy
      and pathological features of cardiac chambers and great vessels. Pulmonary artery
      and its branches, right heart chambers and tricuspid valve, inferior and superior
      vena cava, outflow tract of both ventricles, aortic root, pulmonary veins and
      segmental views of both ventricles are well analyzed. Also in native and
      prosthetic regurgitants jets, cardiac tumors and other masses, diagnosis and
      complications of endocarditis, aortic dissection and in anomalous return of
      pulmonary veins, multiplane probe proves to be more informative. There was no
      difficulties in the intubation despite the bigger size of the transducer. No
      severe complications occurred. The higher price and the initial more difficult
      understanding of the images are the only disadvantages we have found.
      CONCLUSIONS: Multiplane probe contributes to increase diagnostic capability of
      transesophageal echocardiography without significant risk and it is an important
      and promising refinement of the transesophageal technique.

PMID- 7818945
TI  - [Vascular rings: surgical treatment].
AB  - From 1982 to 1992, nine patients underwent correction of vascular rings. The
      diagnosis was strongly suggested by symptoms of tracheoesophageal obstruction and
      was confirmed by barium esophagogram and angiography. Endoscopic studies were
      considered unnecessary and potentially harmful. Seven patients had double aortic
      arch, one patient right aortic arch with aberrant left subclavian artery and left
      ligamentum arteriosum and one patient anomalous origin of the left pulmonary
      artery. The anomaly was approached through a left thoracotomy in every patient.
      There were no operative or late deaths. When patients are symptomatic, vascular
      rings should be promptly repaired. The surgical risk is minimal, and the long
      term results are excellent.

PMID- 7818946
TI  - The problem of cardiovascular disease in southern Europe.

PMID- 7818947
TI  - Toxic effects of bis (tributyltin) oxide on the synthesis and secretion of
      zymogen granules in the rat exocrine pancreas.
AB  - Toxic effects of bis (tributyltin) oxide (TBTO) on the rat exocrine pancreas were
      studied with an electron microscope and X-ray microanalyzer. To measure tin
      concentrations in the blood, atomic absorption spectrophotometry was carried out.
      Adult male Wistar rats received an intramuscular injection of TBTO (0.5 ml/kg).
      At 2 h after injection, a marked swelling of mitochondria and an enlargement of
      the cisterns of the rough endoplasmic reticulum appeared in the pancreatic acinar
      cells. Using X-ray microanalysis, tin peaks were preferentially obtained from the
      swollen mitochondria. Heterogeneous zymogen granules with an electron dense core
      and a pale central zone increased in number in the acinar cells between 4 and 8 h
      after TBTO treatment. By 24 h after TBTO injection, the acinar cells had been
      ultrastructurally restored. Atomic absorption analyses showed that blood tin
      concentrations peaked at approximately 1 h after TBTO injection and then
      progressively declined, reaching the zero level at 12 h after injection. The
      effects of TBTO on the synthesis and secretion of zymogen granules were
      investigated with and without caerulein as a stimulant of secretion. Data
      obtained from these experiments indicated that TBTO inhibited both the synthesis
      and secretion of zymogen granules. The inhibition of the protein synthesis and
      secretion might be caused partly by mitochondrial dysfunctions due to the toxic
      effects of TBTO.

PMID- 7818949
TI  - Langerhans cells closely associated with Thy-1-positive dendritic cells in the
      stratified squamous mucosal epithelium of mice.
AB  - An immunohistochemical study was carried out on two types of dendritic immune
      cells, Langerhans cells and Thy-1-positive cells, in the epithelium of the
      forestomach of 1-, 2-, 3-, 4- and 8-week-old mice. Investigation focused on how
      both types of cells were distributed and might interact in the mucosal
      epithelium. Langerhans cells and Thy-1-positive dendritic cells appeared in
      mucosal epithelium at 3 weeks of age, while in the epidermis they were first
      observed just after birth. In contrast with the epidermal Thy-1-positive cells,
      mucosal Thy-1-positive cells were closely associated with Langerhans cells.
      Electron microscopy also confirmed that two types of immune cells interact
      directly in the stratified squamous mucosal epithelium of mice.

PMID- 7818948
TI  - The vascularization of the pituitary gland of the chicken (Gallus domesticus). A
      scanning electron microscope study of vascular corrosion casts.
AB  - Microvascular corrosion casts of the pituitary gland of one to nine-day-old
      chickens (Gallus domesticus, white leghorn hybrids) were analysed with the
      scanning electron microscope. Results show that the chicken median eminence is
      supplied by branches of the infundibular and the neural-lobe arteries. They form
      a flat two-dimensional primary capillary plexus, which lacks any capillary loops
      and is continuous with the plexus in the neural lobe. The capillaries occupy
      about 60% of the total area of the median eminence. A subependymal plexus is
      present, showing no contact with the plexus of the median eminence. The chicken
      neural lobe consists of many hollow buds. These buds are supplied by branches of
      the neural-lobe artery, which gives rise to a two-dimensional capillary meshwork
      similar to that of the median eminence. An anterior group of portal vessels,
      comprising 14-16 vessels with a mean diameter of 37 microns, and a posterior
      group of portal vessels, comprising 2-4 shorter and slightly thinner vessels,
      arise from the median eminence are the sole blood supply for the adenohypophysis
      (distal lobe). Anterior portal vessels supply the cephalic lobe and the most
      rostral area of the caudal lobe, and posterior portal vessels supply the caudal
      lobe of the distal lobe. There are no short portal vessels connecting the neural
      lobe with the distal lobe. The (sinusoidal) capillary bed of the distal lobe is
      laminated. The chicken hypophysis drains into the cavernous sinus, which empties
      into the cerebral carotid veins. Within the period studied (days 1-9 after
      hatching) no age-related changes were found.

PMID- 7818950
TI  - Lamina propria macrophages involved in cell death (apoptosis) of enterocytes in
      the small intestine of rats.
AB  - In the rat small intestine, apoptotic enterocytes are exfoliated at the villus
      tip as a whole cell, in contrast to guinea pig enterocytes which are phagocytosed
      by macrophages in their cell body and shed off only in their apical cortex. While
      macrophages gather in the lamina propria of the intestinal villi in both species,
      their functions seem to differ. Unlike the guinea pig, lamina propria macrophages
      observed in the rat small intestine did not show morphological signs of
      phagocytosis, revealing few cellular elements in their phagosomes. At the
      "shoulder" of the villus, i.e., a certain distance proximal to the villus tip,
      subepithelial macrophages extended a thick process deep into the epithelium;
      their branched terminals penetrated the cytoplasm of enterocytes, resulting in
      the formation of excavated spaces in the cell body. Processes of macrophages
      frequently reached close to the brush border. At the shoulder of the villus, a
      few effete cells showed typical apoptotic signs and appeared to be pushed out
      into the lumen; still, the shedding of apoptotic enterocytes was recognized
      mainly at the very top of the villus, where no intraepithelial processes of
      macrophages could be seen. The present findings indicate that in the rat, lamina
      propria macrophages do not engulf aged enterocytes, but are involved in inducing
      their apoptosis.

PMID- 7818951
TI  - Adrenergic innervation of the urinary bladder body in the cat with special
      reference to structure of the detrusor muscle: an immunohistochemical study of
      noradrenaline and its synthesizing enzymes.
AB  - The distribution of adrenergic nerves in the body detrusor muscle of the cat
      urinary bladder was studied by means of the immunohistochemical identification of
      noradrenaline (NA) and the NA synthesizing enzymes tyrosine hydroxylase, aromatic
      L-aminoacid decarboxylase and dopamine beta-hydroxylase. We identified the basic
      structural organization of the detrusor muscle, which had previously been
      described as lacking discernible layers. In the lateral wall, both outer
      longitudinal and inner circular muscle bundles were present, the latter extending
      in both anterior and posterior directions. The posteriorly running bundles came
      to lie on the outside of the posterior wall where they enabled recognition of
      inner longitudinal muscle bundles. Those running anteriorly were dispersed to
      enter the longitudinal bundles in the anterior wall. NA-immunoreactive nerve
      fibers in the detrusor muscle of the bladder were found to be similar to those
      immunoreactive for NA synthesizing enzymes in both distribution and density. In
      the upper and middle bladder body--including the dome (apex)--immunoreactive
      nerve fibers were always more abundant in the outer part of the detrusor muscle
      than in the inner part, regardless of the course of muscle bundles. Even in
      individual muscle bundles running from the inside to the outer surface, the outer
      part was more richly innervated by immunoreactive fibers than the inner part. In
      the bladder dome, a moderate number of immunoreactive nerve fibers preferentially
      innervated the outer part of the muscle layer. In the lower bladder body, these
      nerve fibers increased in density in the inner part of the detrusor muscle. There
      was no sexual difference in density or distribution of nerve fibers. NA- and NA
      synthesizing enzyme-immunoreactive nerve fibers were markedly decreased in number
      after 6-hydroxydopamine treatment. No dopamine- or phenylethanolamine-N
      methyltransferase-immunoreactive nerve fibers were present in the bladder. The
      findings of this study indicate that the cat bladder musculature includes
      longitudinal and circular muscle bundles, both of which are extensively
      innervated by adrenergic nerves, particularly in the outer part of the bladder.

PMID- 7818953
TI  - Morphology and molecular biology: can the latter ignore the former? An imaginary
      dialogue.

PMID- 7818952
TI  - Ontogeny of milky spots in the fetal lamb omentum.
AB  - Milky spots in the fetal lamb omentum were observed by light and electron
      microscopy under normal conditions and after intraperitoneal carbon injection in
      utero. Rudimentary milky spots first appeared as small aggregations of cells
      along capillaries of the omental branch of the right ruminal artery at 72 days of
      gestation. At 116 days of gestation, macrophages were detected
      immunohistochemically in the milky spots. At 125 days of gestation, T cells were
      detected in the milky spots, but B cells were absent. Under the conditions
      induced by intraperitoneal injection of carbon suspension, openings were observed
      between the omental mesothelial cells, and macrophage aggregations appeared on
      the surface of the omentum through the openings. At 148 days of gestation
      (newborn), the milky spots were noted as black spots because of aggregation of
      carbon laden macrophages. The present study demonstrates that milky spots are
      present at fixed sites in the fetal lamb omentum by the middle of the term, and
      that at birth the macrophages on the spots already possess phagocytotic ability.
      The fetus develops the ability to protect the peritoneal cavity by producing
      peritoneal macrophages from the milky spots in the greater omentum even in utero.

PMID- 7818954
TI  - Advances in rate responsive pacing?

PMID- 7818955
TI  - Appropriate indications for radiofrequency catheter ablation.

PMID- 7818956
TI  - Effect of bystander initiated cardiopulmonary resuscitation on ventricular
      fibrillation and survival after witnessed cardiac arrest outside hospital.
AB  - OBJECTIVE: To describe the proportion of patients who were discharged from
      hospital after witnessed cardiac arrest outside hospital in relation to whether a
      bystander initiated cardiopulmonary resuscitation. PATIENTS: All patients with
      witnessed cardiac arrest outside hospital before arrival of the ambulance and in
      whom cardiopulmonary resuscitation was attempted by the emergency medical service
      in Gothenburg during 1980-92. RESULTS: Cardiopulmonary resuscitation was
      initiated by a bystander in 18% (303) of 1,660 cases. In this group 69% had
      ventricular fibrillation at first recording compared with 51% in the remaining
      patients (P < 0.001). Among patients in whom cardiopulmonary resuscitation had
      been initiated by a bystander 25% were discharged alive versus 8% of the
      remaining patients (P < 0.001). Independent predictors of survival were in order
      of significance: initial arrhythmia (P < 0.001), interval between collapse and
      arrival of first ambulance (P < 0.001), cardiopulmonary resuscitation initiated
      by a bystander (P < 0.001), and age (P < 0.01). Among patients who were admitted
      to hospital alive 30% of patients in whom cardiopulmonary resuscitation had been
      initiated by a bystander compared with 58% of remaining patients (P < 0.001) had
      brain damage and died in hospital. Corresponding figures for death in association
      with myocardial damage were 18% and 29% respectively (P < 0.01). CONCLUSIONS:
      Cardiopulmonary resuscitation initiated by a bystander maintains ventricular
      fibrillation and triples the chance of surviving a cardiac arrest outside
      hospital. Furthermore, it seems to protect against death in association with
      brain damage as well as with myocardial damage.

PMID- 7818957
TI  - Insulin resistance, high prevalence of diabetes, and cardiovascular risk in
      immigrant Asians. Genetic or environmental effect?
AB  - OBJECTIVES: To compare the prevalence of diabetes, hyperinsulinaemia, and
      associated metabolic abnormalities in immigrant Asians, Asians in India, and
      native white British men. DESIGN: Case control study. SETTING: Wythenshawe
      Hospital, Manchester, United Kingdom, and Maulana Azad Medical School, New Delhi,
      India. SUBJECTS: Men with angiographically proved coronary artery disease; 83
      British Asians, 87 white men, and 30 Indian Asians with age matched controls.
      INTERVENTIONS: Fasting lipid concentrations, serum glucose, and total insulin
      concentrations were measured in the fasting state and one and two hours after a
      75 g glucose load by mouth. All subjects had a physical examination by the same
      observer. RESULTS: Asians in the United Kingdom and in India had a higher
      prevalence of diabetes and impaired glucose tolerance than the white British men.
      Patients in all three ethnic groups had higher total insulin concentrations than
      their controls in the fasting state and after the glucose load. British Asian and
      Indian Asian patients and controls had higher total insulin concentrations than
      the white men in the fasting state and after the glucose load. Total insulin
      concentrations were similar in British and Indian Asians, though fasting
      concentrations were higher in British Asians than Indian Asians. White men had
      similar cholesterol, lower triglyceride, and higher high density lipoprotein
      cholesterol concentrations than Asians in the United Kingdom and in India.
      British Asian patients had higher cholesterol concentrations and British Asian
      controls had higher triglyceride concentrations than the Indian Asian groups.
      Asian patients and controls were more active. British and Indian Asian patients
      had higher waist to hip ratios than controls. The waist to hip ratio was
      positively correlated with insulin and triglyceride concentrations and negatively
      correlated with the high density lipoprotein cholesterol concentration. Fasting
      insulin and high density lipoprotein concentrations were independent predictors
      of coronary artery disease in white men, whereas in British Asians the waist to
      hip ratio was the strongest independent predictor. In Indian Asians the waist to
      hip ratio and high density lipoprotein concentration were independent predictors
      of coronary artery disease. CONCLUSIONS: Central obesity in the subgroups of
      Asians studied showed a close association with hyperinsulinaemia and the risk of
      coronary artery disease. A predisposition to insulin resistance and its metabolic
      abnormalities in this group of Asians seems to be genetically determined,
      environmental changes after migration having only a small additional effect.

PMID- 7818958
TI  - Neurohormonal activation in patients with mild or moderately severe congestive
      heart failure and effects of ramipril. The Ramipril Trial Study Group.
AB  - OBJECTIVES: To describe neurohormonal activation in patients with mild or
      moderate heart failure and how it may be modified by treatment with ramipril.
      SETTING: Cardiology departments at 24 hospitals in Denmark, Finland, Norway, and
      Sweden. PATIENTS: 223 patients with mild or moderately severe congestive heart
      failure who were taking diuretics with or without digitalis. DESIGN: Randomised,
      double bind, multicentre, placebo controlled comparison of ramipril and placebo.
      Venous blood samples were drawn at rest, before blind treatment, and after 12
      weeks of treatment with the study drug. A probability prediction score for
      mortality derived by stepwise linear discriminant from neurohormone data in the
      first cooperative north Scandinavian enalapril survival study (CONSENSUS I) was
      used to assess combined activity of the different neurohormonal systems. RESULTS:
      Plasma concentrations of atrial natriuretic peptide were raised at baseline but
      angiotensin II, aldosterone, and noradrenaline concentrations were within normal
      limits. There was, however, a wide interindividual variation. Plasma
      noradrenaline concentration and prediction score were higher among patients with
      class III congestive heart failure according to the New York Heart Association's
      classification than among patients with class II congestive heart failure (P <
      0.05). There was a modest but significant inverse correlation between exercise
      duration at baseline and plasma noradrenaline concentration (r = -0.21, P =
      0.0023), aldosterone concentration (r = -0.14, P = 0.04), and prediction score (r
      = -0.24, P = 0.0004). Prediction score at baseline was significantly higher among
      those who died (n = 10) than among survivors (P = 0.03). Angiotensin converting
      enzyme activity was suppressed and plasma concentrations of aldosterone and
      atrial natriuretic peptide were reduced after 12 weeks of treatment with ramipril
      compared with placebo. In patients with the most pronounced neurohormonal
      activation at baseline (highest third of noradrenaline concentration or
      prediction score), noradrenaline concentration and prediction score were
      significantly lower after 12 weeks of taking ramipril compared with placebo.
      Patients with a prediction score in the highest third at baseline had a higher
      heart rate than to those in the lowest third (P = 0.003). CONCLUSIONS:
      Neurohormonal activation is associated with the degree of symptoms and the
      severity of disease in mild or moderately severe congestive heart failure.
      Treatment with ramipril attenuates neurohormonal activation. This effect is most
      pronounced among patients with the highest circulating concentrations of
      neurohormones before the start of treatment.

PMID- 7818959
TI  - Emergency surgical revascularisation for coronary angioplasty complications.
AB  - OBJECTIVES: To evaluate trends in referrals for emergency operations after
      percutaneous transluminal coronary angioplasty (PTCA) complications; to analyse
      morbidity and mortality and assess the influence of PTCA backup on elective
      surgery. DESIGN: A retrospective analysis of patients requiring emergency
      surgical revascularisation within 24 hours of percutaneous transluminal coronary
      angioplasty. PATIENTS: Between January 1980 and December 1990, 75 patients
      requiring emergency surgery within 24 hours of percutaneous transluminal coronary
      angioplasty. SETTING: A tertiary referral centre and postgraduate teaching
      hospital. RESULTS: 57 patients (76%) were men, the mean age was 55 (range 29-73)
      years, and 30 (40%) had had a previous myocardial infarction. Before PTCA, 68
      (91%) had severe angina, 59 (79%) had multivessel disease, and six (8%) had a
      left ventricular ejection fraction of less than 40%. A mean of 2.1 grafts (range
      one to five) were performed; the internal mammary artery was used in only one
      patient. The operative mortality was 9% and inhospital mortality was 17%. There
      was a need for cardiac massage until bypass was established in 19 patients (25%):
      this was the most important outcome determinant (P = 0.0051) and was more common
      in those patients with multivessel disease (P = 0.0449) and in women (P =
      0.0388). In 10 of the 19 cases a vacant operating theatre was unavailable, the
      operation being performed in the catheter laboratory or anaesthetic room. These
      19 patients had an operative mortality of 32% and inhospital mortality of 47%,
      compared with 2% and 7% respectively for the 56 patients who awaited the next
      available operating theatre. Complications included myocardial infarction, 19
      patients (25%); arrhythmias, 10 patients (3%); and gross neurological event, two
      patients (3%). The mean intensive care unit stay was 2.6 days (range 1 to 33
      days) and the mean duration of hospital admission was 13 days (range 5-40 days).
      CONCLUSIONS: Patients undergoing emergency surgery after PTCA complications have
      a substantially increased inhospital mortality and morbidity. PTCA in this unit
      continues to require surgical cover. Delays in operating on stable patients in
      centres which operate a "next available theatre" backup policy may not differ
      from some units performing PTCA with offsite cover for PTCA complications.
      Particularly in the presence of multivessel disease, however, PTCA complications
      may be associated with the need for "crash" bypass and such patients are unlikely
      to survive hospital transfer. The proportion of patients requiring "crash" bypass
      has increased during the period reviewed because of the extent of disease in the
      emergency surgical group increased. These results indicate that surgery should
      not be denied to these patients.

PMID- 7818961
TI  - Non-smoke spontaneous contrast in left atrium intensified by respiratory
      manoeuvres: a new transoesophageal echocardiographic observation.
AB  - OBJECTIVE: To elucidate why different types of contrast appear in the left atrium
      during transoesophageal echocardiographic contrast studies. This should lead to a
      more uniform definition of true patent foramen ovale. BACKGROUND: The Valsalva
      manoeuvre and cough are routinely used to enhance right to left shunt for the
      detection of patent foramen ovale. No information is, however, available on the
      effect of these manoeuvres on the intrinsic echogenicity of blood in the left
      atrium. METHODS: 30 consecutive patients referred for transoesophageal
      echocardiography were studied. Gain settings were relatively high so that no
      details were lost. The appearance of contrast during normal respiration, cough,
      and the Valsalva manoeuvre was looked for in the left atrium with and without
      venous injection of 10 ml of 5% dextrose. Frequency of contrast appearance in the
      left atrium was expressed as a percentage. Intensity of contrast, when present,
      was graded 1 (mild), 2 (moderate), or 3 (equal to right atrial contrast during
      injection). Timing was assessed in cardiac cycles after the end of respiratory
      manoeuvres. RESULTS: Left atrial contrast appeared as a "snowstorm" flowing from
      the right pulmonary veins towards the middle of the left atrium. It was present
      respectively with and without contrast injection in eight and five patients
      during normal respiration, in 15 and seven during a cough, and in 20 and 14
      during the Valsalva manoeuvre. When present, the mean intensity of contrast was
      1.0 during normal respiration, 1.4 during a cough, and 1.4 during the Valsalva
      manoeuvre. The mean delay of contrast appearance was 3-4 cycles after release of
      the Valsalva manoeuvre and after onset of cough. CONCLUSIONS: Respiratory
      manoeuvres frequently induce the transient appearance of mild to moderate
      contrast in the left atrium, most often independently of venous injections. Mild
      contrast was seen only with high gain settings. This contrast is likely to be
      related to transient stasis in the pulmonary circulation. In some cases
      peripheral venous injections of dextrose solution produced, without any
      respiratory manoeuvre, a similar contrast after the first four cardiac cycles of
      the right atrium filling, which is likely to represent recirculation of the
      injected bolus through the pulmonary capillary bed. Therefore respiratory
      manoeuvres should always be performed before contrast injections to allow better
      distinction between this background and true patent foramen ovale or pulmonary
      arteriovenous fistula.

PMID- 7818960
TI  - Raised plasma endothelin in unstable angina and non-Q wave myocardial infarction:
      relation to cardiovascular outcome.
AB  - BACKGROUND: Among patients with independent evidence of coronary disease and
      recent onset unstable angina or non-Q wave myocardial infarction the incidence of
      subsequent cardiovascular events is high. Markers predictive of adverse cardiac
      outcome in unstable angina and non-Q wave myocardial infarction need to be
      defined more accurately. Endothelin-1 is a potent endothelium derived
      vasoconstrictor peptide that may play a part in the pathophysiology of acute
      myocardial ischaemia. AIM AND STUDY DESIGN: In a study that specifically
      identified high risk patients a group of 16 consecutive patients with either
      unstable angina at rest or non-Q wave myocardial infarction were prospectively
      investigated to establish whether these conditions are associated with high
      plasma immunoreactive endothelin and whether endothelin concentration at
      presentation is related to cardiovascular events within the next 12 weeks.
      Controls consisted of a group of 40 healthy subjects. RESULTS: Patients had
      significantly higher mean (SD) plasma endothelin at presentation than did healthy
      controls (7.4 (1.1) v 5.0 (1.2) pg/ml, P < 0.0001). At nine weeks plasma
      endothelin was still significantly higher in those patients who had subsequent
      cardiovascular events, (n = 9, acute myocardial infarction or refractory angina
      with electrocardiographic changes and revascularisation procedures, 8.5 (2.6)
      pg/ml, P < 0.005 v controls) whereas its concentration returned to normal in
      those patients who had a favourable outcome (n = 7, 5.9 (0.7) pg/ml). Compared
      with those patients who had an uneventful course, patients with subsequent events
      had significantly higher plasma endothelin, both at presentation and at nine
      weeks (P < 0.05 on both occasions). IMPLICATIONS: Endothelin may contribute to
      the pathophysiology of acute coronary syndromes and may relate to subsequent
      cardiovascular outcome.

PMID- 7818962
TI  - Effect of intracardiac repair on biosynthesis of thromboxane A2 and prostacyclin
      in children with a left to right shunt.
AB  - OBJECTIVE: To investigate the effect of intracardiac repair on the abnormal
      biosynthesis of prostacyclin (PGI2) and thromboxane A2 (TXA2) in children with
      congenital heart disease and increased pulmonary blood flow. DESIGN: A
      prospective study with immunoaffinity chromatography and gas chromatography-mass
      spectrometry to measure the urinary excretion products of PGI2 (2,3-dinor-6-oxo
      prostaglandin (PG) F1 alpha (2,3-dinor-6-oxo-PGF1 alpha)) and TXA2 (2,3-dinor
      TXB2) before operation, in the first 12-24 h after operation, and at discharge
      from hospital. SETTING: A supraregional referral centre for patients with
      congenital heart disease. PATIENTS: 15 patients aged 2 to 60 months (median 7
      months) with a left to right shunt who underwent intracardiac repair. RESULTS:
      The preoperative 2,3-dinor-TXB2 excretion rate was greater than that found
      previously in a control group of 16 healthy children with a median (range) age of
      24 (6-36) months (1159(201) v 592(122) ng/g creatinine in controls, P = 0.006).
      The excretion rate rose after operation to 9600(3832) ng/g creatinine (P = 0.01)
      and decreased before discharge to 1071(191) ng/g creatinine (NS), but remained
      greater than that of the control group (P = 0.014). Before operation 2,3-dinor-6
      oxo-PGF1 alpha excretion rates were similar to those of the healthy children
      (482(68) v 589(95) ng/g creatinine in controls) but increased after operation to
      19,668(11,162) ng/creatinine (P = 0.002) and fell at discharge to 1621(245) ng/g
      creatinine although this was higher than both preoperative and control rates (P =
      0.005 and P = 0.0002 respectively). The preoperative ratio of 2,3-dinor-TXB2 to
      2,3-dinor-6-oxo-PGF1 alpha excretion was greater than that of the control group
      (3.2(0.8) v 1.3(0.22) in controls, (P = 0.005)), decreased significantly after
      operation to 0.9(0.13) (P = 0.016), and changed little, to 0.7(0.12), before
      discharge. The last two ratios were similar to those in normal children and
      significantly lower than those before operation (P = 0.004). CONCLUSION: In
      children with a left to right shunt the ratio of the excretion rates of the
      metabolites of TXA2 and PGI2 was abnormal before operation, which favoured
      vasoconstriction and platelet aggregation, but had decreased at discharge from
      hospital. The increase in excretion of PGI2 metabolites over TXA2 metabolite
      after intracardiac repair augurs well for pulmonary vascular recovery.

PMID- 7818964
TI  - Transoesophageal echocardiography as the sole diagnostic investigation in
      patients with suspected thoracic aortic dissection.
AB  - OBJECTIVES: To assess the value and limitations of using transoesophageal
      echocardiography as the sole diagnostic test in patients with suspected thoracic
      aortic dissection. DESIGN: Retrospective data review over a two year period.
      SETTING: A regional cardiothoracic centre. PATIENTS: Data were compiled from
      admission records, surgical records, and lists of patients undergoing diagnostic
      investigations in the hospital. Patient's notes were used to identify
      presentation, management, and outcome. INTERVENTIONS: Patients were managed
      according to the policy of our unit, which is to treat patients with dissection
      affecting the ascending aorta by an operation. Patients with uncomplicated
      dissection sparing the ascending aorta are initially managed medically. MAIN
      OUTCOME MEASURES: In hospital and two year follow-up of patients who were
      investigated by transoesophageal echocardiography alone. RESULTS: Of 48 patients
      referred, 45 underwent transoesophageal echocardiography. Dissection was
      confirmed in 22 patients. Transoesophageal echocardiography showed the proximal
      extent of the dissection in 21/22 (96%) and only one patient required a further
      diagnostic investigation. Ten patients with dissection of the ascending aorta
      underwent graft replacement of the ascending aorta; operative mortality was 10%
      and their two year survival was 80%. Of the eight patients with dissection of the
      descending aorta, six were discharged home, and five were alive at two years. No
      patient without evidence of dissection on their initial transoesophageal
      echocardiographic examination required re-investigation into possible dissection
      in the two years after discharge. CONCLUSIONS: In patients with suspected
      thoracic dissection transoesophageal echocardiography rapidly and safely gives
      all the necessary diagnostic information. Further investigations, including
      coronary angiography, before surgery are unnecessary.

PMID- 7818963
TI  - Temporary iatrogenic fetal tricuspid valve atresia in a case of twin to twin
      transfusion syndrome.
AB  - This report describes the sequence of events in the development and subsequent
      spontaneous resolution of functional tricuspid valve atresia in the donor fetus
      in a case of twin to twin transfusion syndrome. Fetoscopic laser coagulation of
      the placental anastomoses was performed at 20 weeks' gestation. Subsequently,
      there was evidence of increased placental vascular resistance in the donor twin
      and major impairment of right ventricular function with no forward flow through
      the tricuspid valve. During the next four weeks, however, there was spontaneous
      and complete recovery of ventricular function and resolution of the functional
      tricuspid valve atresia. These findings suggest that alterations in fetal
      haemodynamics may result in structural cardiac abnormality and may be the
      precursors of some forms of congenital heart disease.

PMID- 7818965
TI  - Inadequate management of hyperlipidaemia after coronary bypass surgery shown by
      medical audit.
AB  - OBJECTIVE: To audit the detection and management of hyperlipidaemia in patients
      who have had coronary bypass surgery. PATIENTS: 100 consecutive patients (81
      men), mean age 61, who had survived at least 3 months after coronary bypass
      surgery. METHODS: Retrospective review of case notes and computerised
      biochemistry records. RESULTS: 83 patients had at least one lipid measurement in
      the hospital, and of the remaining 17 patients, 10 had undergone urgent or
      emergency surgery. The median (range) total cholesterol was 6.7 (4.0-11.7) mmol/l
      and the triglyceride concentration was 2.1 (0.6-18.4) mmol/l. Only 30 patients
      were referred to a dietician, and 12 were given a lipid lowering drug--these
      interventions were no more frequent in patients with a cholesterol concentration
      above than below the median. CONCLUSIONS: Although a high proportion of patients
      who undergo routine coronary bypass surgery have their plasma lipid
      concentrations measured, many patients with raised cholesterol concentrations,
      who would benefit from lipid lowering interventions, are not offered them.

PMID- 7818966
TI  - A cautionary tale of undetected hyperlipidaemia: implications for coronary artery
      bypass grafting.

PMID- 7818967
TI  - Percutaneous transcatheter retrieval of misplaced therapeutic embolisation
      devices.
AB  - OBJECTIVE: To assess the incidence and subsequent management of misplaced devices
      as a complication of therapeutic embolisation procedures. DESIGN: Retrospective
      review of case notes, cardiac catheterisation reports, and angiograms. SETTING:
      Tertiary referral centre for congenital heart disease. PATIENTS: 205 consecutive
      children and adults undergoing therapeutic embolisation for congenital heart
      disease in the 10 years up to 1 April 1993. This group had 231 therapeutic
      embolisation procedures at 241 sites using coils, umbrella devices, or detachable
      balloons. MAIN OUTCOME MEASURES: Incidences of misplacement and retrieval of the
      device; morbidity and mortality. RESULTS: The incidence of misplacement was 3%
      (10/332) of devices deployed and 4.3% (10/231) of procedures performed. Retrieval
      from distal pulmonary arteries was not attempted in two patients, but
      transcatheter retrieval of coils and umbrellas from systemic and pulmonary
      vessels, using snares or retrieval baskets, was successful in the remaining
      eight. There were no deaths or serious sequelae related to the procedure, but one
      patient required femoral arteriotomy for removal of an umbrella device retrieved
      only as far as the groin. In four of the five most recent cases, the misplaced
      device was retrieved and the therapeutic embolisation was completed at the same
      procedure. CONCLUSIONS: Misplacement of a device during therapeutic embolisation
      is a recognised complication that can be satisfactorily dealt with by
      transcatheter retrieval without recourse to surgery. For retrieval to be
      successful it is important to have a wide selection of retrieval equipment
      available and to be conversant with its use.

PMID- 7818968
TI  - Transcutaneous ultrasound assessment of internal thoracic artery to coronary
      artery grafts in patients with and without ischaemic symptoms.
AB  - OBJECTIVE: To evaluate transcutaneous duplex ultrasound in the assessment of
      internal thoracic artery to coronary artery grafts. SETTING: Regional
      cardiothoracic centre. METHODS: Prospective duplex ultrasound evaluation of 83
      consecutive patients undergoing left internal thoracic artery to coronary artery
      grafts, together with combined angiographic and duplex ultrasound evaluation of
      17 patients with suspected recurrent myocardial ischaemia after internal thoracic
      artery grafting. RESULTS: The grafted internal thoracic artery was imaged in 65
      (78%) of 83 consecutive postoperative patients, and in 13 (75%) of 17 patients
      with suspected graft dysfunction. Grafts were recognised by their characteristic
      position and biphasic blood flow pattern. Resting graft flow was estimated from
      the time averaged velocity and graft cross sectional area. Median resting flow in
      patients without ischaemic symptoms was 36 ml/min (interquartile range 24 to 49
      ml/min). Of 13 patients with recurrent ischaemia in whom the graft could be
      imaged, nine patients with estimated flow in the lowest quartile or abnormal flow
      profiles, or both, had graft disease or anastomotic problems on angiography,
      while four with satisfactory graft flow on ultrasound examination had normal
      graft flow on angiography, but had evidence of native disease progression in
      other vessels. Two of four patients in whom it was not possible to image the
      graft on ultrasound had satisfactory graft function on angiography. CONCLUSIONS:
      For those patients whose internal thoracic artery graft can be imaged,
      transcutaneous duplex ultrasound is a helpful non-invasive guide to graft
      function. The main limitations to the technique are an inability to image the
      graft in about 20% of patients, and possible inaccuracy in estimating graft
      diameter.

PMID- 7818969
TI  - Balloon dilatation of complete obstruction of the superior vena cava after
      Mustard operation for transposition of great arteries.
AB  - Balloon dilatation was successfully performed in two patients with complete
      obstruction of the superior vena cava baffle junction after a Mustard operation
      for transposition of the great arteries. Evidence for complete relief of
      obstruction in the first patient, aged 4 years, was obtained by angiography,
      which showed improved calibre at the site of obstruction and improved
      haemodynamic pressure measurement after the balloon dilatation. In the second
      patient, aged 14 years, the relief was incomplete; in this patient a 3 cm long 3
      mm diameter Palmaz stent was successfully implanted.

PMID- 7818970
TI  - A comparison of cylindrical and Inoue balloon techniques for mitral valvotomy in
      patients in the United Kingdom.
AB  - OBJECTIVES: To compare the use of cylindrical balloons and the Inoue balloon for
      percutaneous mitral valvotomy in patients in the United Kingdom. DESIGN:
      Comparison of the haemodynamic results, complications, and symptomatic outcome of
      balloon dilatation for mitral stenosis in consecutive patients treated by
      cylindrical balloons and a second consecutive series of patients treated by the
      Inoue balloon. SETTING: A tertiary cardiac referral centre in Scotland. PATIENTS:
      70 patients (mean age 60.6 years) treated by the single or double cylindrical
      balloon technique and 70 patients (mean age 58.9 years) treated with the Inoue
      balloon method. MAIN OUTCOME MEASURES: Success in obtaining dilatation at the
      mitral orifice, procedure and screening times, increase in valve area,
      complications, and early symptomatic outcome. RESULTS: Dilatation of the mitral
      valve was obtained in 91% of patients when cylindrical balloons were used and in
      99% of patients treated with the Inoue balloon. Use of the Inoue balloon gave
      significantly shorter procedure and screening times. Technical problems in
      obtaining and maintaining the position at the mitral orifice were more common
      with cylindrical balloons. Improvements in valve area and symptoms were not
      significantly different with use of the two types of balloon. The Inoue balloon
      avoided cardiac tamponade and the creation of larger atrial septal defects, but
      had a higher incidence of increase in mitral reflux. CONCLUSIONS: In these
      elderly patients, the Inoue balloon method was safer and faster for percutaneous
      mitral valvotomy, with a higher success rate for dilatation within the valve
      orifice. Haemodynamic and symptomatic improvement was similar with the two
      techniques.

PMID- 7818971
TI  - Is ventricular ectopy a legitimate target for ablation?
AB  - Radiofrequency ablation has an established role in the treatment of non-ischaemic
      ventricular tachycardia. A few patients present with symptomatic but benign
      ventricular ectopy that can be mapped to the right ventricular outflow tract. The
      successful use of radiofrequency ablation in a patient with drug resistant,
      symptomatic ventricular ectopy is reported. Radiofrequency ablation may have a
      useful role in more benign arrhythmias.

PMID- 7818972
TI  - Persistent root abscess after emergency repair with an aortic homograft.
AB  - A fifty eight year old man with Marfan's syndrome and an aortic composite graft
      with a Bjork-Shiley mechanical prosthesis presented with a large aortic root
      abscess caused by Staphylococcus aureus endocarditis. Despite extensive surgical
      debridement and implantation of an aortic homograft as a composite graft, early
      postoperative transoesophageal echocardiography continued to demonstrate a large
      aortic root abscess and the patient died in a septic shock.

PMID- 7818973
TI  - Preoperative assessment of cor triatriatum in an adult by dynamic three
      dimensional echocardiography was more informative than transoesophageal
      echocardiography or magnetic resonance imaging.
AB  - Classic cor triatriatum is rarely found in adults. Preoperative assessment of
      classic cor triatriatum in a 22 year old man without symptoms by three
      dimensional echocardiography was more informative than transoesophageal
      echocardiography or magnetic resonance imaging, which both showed only a small
      hole in the membrane separating the accessory atrium from the true left atrium.
      The size of the hole indicated a strong likelihood that symptoms would develop in
      this patient. Dynamic three dimensional echocardiography, however, showed a long
      wide hole in the separating membrane. This finding was consistent with the
      absence of symptoms in this patient. Symptom free patients with moderate
      obstruction do not need early surgical correction.

PMID- 7818974
TI  - A comparison of HIV risk between women and men who inject drugs.
AB  - Although there is growing evidence of differences between women and men who
      inject drugs (IDUs) in terms of level of risk for HIV infection, very little
      research has been conducted specifically addressing the risk practices of women
      IDUs. This study formed part of a national study of HIV infection risks in IDUs
      and the purpose of the present analysis was an exploration of gender differences
      in HIV risk practices, focusing on the HIV risk practices of IDU women. 1,245
      IDUs from the inner city area of Sydney took part in this study. Of these, 908
      were men and 331 were women. Notable results were that female respondents were
      more likely to report sharing needles, they injected heroin more times in a
      typical using month and were more likely to have shared with someone they later
      found out was HIV seropositive. Female respondents also reported more sexual
      partners than men, were more likely to engage in prostitution, and were more
      likely to have sexual partners who were themselves IDUs. The results provide
      support for the proposition that women who inject drugs may be at greater risk of
      HIV infection through both their drug taking and their sexual practices. Further
      research is needed to explore the reasons underlying the risk practices of women
      who inject drugs and an understanding of these factors needs to be incorporated
      into HIV risk-reduction and drug harm-reduction policies and programs.

PMID- 7818976
TI  - Self-disclosure of HIV infection to sexual partners after repeated counseling.
AB  - This study, with the objective of examining voluntary self-disclosure of HIV
      infection after repeated counseling, was conducted in a private setting, and
      designed to operate in conjunction with HIV testing. Counseling was provided at
      entry, and then at 3 months, 6 months, and every six months thereafter. The study
      was conducted among 129 HIV-positive adults; the primary risk factor was history
      of: males having sex with males (n = 104); injection drug use (n = 19); or
      heterosexual contact (n = 6). Results showed that after a mean of 2.3 years since
      initial HIV-positive notification, 29 percent of subjects had not disclosed the
      HIV infection to any present partner, and 30 percent to any past sex partner.
      Casual sex and lower perceived social support were significantly associated with
      nondisclosure. The authors conclude that even after repeated individual
      counseling and at least several months to inform others, about one-third of the
      sexually active subjects did not disclose their HIV infection to any present sex
      partner. Clinical and public health implications are covered.

PMID- 7818975
TI  - HIV-infected women and sexual risk reduction: the relevance of existing models of
      behavior change.
AB  - This article utilizes constructs of the AIDS Risk Reduction Model (ARRM) to
      examine condom use in a sample of 215 HIV-infected women in New Jersey. We find
      evidence that processes affecting condom use in HIV-infected individuals are
      similar to those found in HIV-negative individuals. Results suggest that partner
      related factors are important to consistent condom use in HIV-infected women.
      Women are more likely to use condoms consistently if they have high perceived
      power to influence their partner's condom use, have partners who are HIV
      seronegative, and have partners who do not want more children. Conflicts with the
      partner decrease the probability of consistent condom use. Also negatively
      associated with condom use are the woman's use of drugs and/or alcohol and her
      belief that condoms reduce sexual enjoyment. Implications of these findings for
      designing interventions for HIV-infected women are considered.

PMID- 7818977
TI  - Evaluation of a theory-based HIV prevention intervention for college students.
AB  - This study tested the effectiveness of a workshop for college students designed
      to increase HIV-preventive behavior by increasing participants' self-efficacy
      concerning HIV-preventive behavior. The Safer Sex Efficacy Workshop (SSE
      workshop) was compared with a lecture on HIV (HIV lecture) and a lecture on an
      unrelated topic, family violence (FV lecture); the effect of each condition on
      self-efficacy, behavioral intentions, and HIV-preventive behavior was assessed.
      Participants in the SSE workshop and the HIV lecture increased more from pretest
      to posttest in self-efficacy and the intention to use a condom than participants
      in the FV lecture. Participants in the SSE workshop increased their frequency of
      condom use from pretest to two-month follow-up more than participants in either
      of the two control conditions. Changes in the frequency of participants'
      discussion of AIDS and past partners with sexual partners and the intention to
      discuss did not differ among the three intervention conditions.

PMID- 7818978
TI  - Cognitive-behavioral group intervention to assist substance-dependent adolescents
      in lowering HIV infection risk.
AB  - Substance dependent adolescents (N = 19), court referred into a residential drug
      treatment facility received a five-session HIV risk-reduction intervention that
      provided risk education, social competency skills (sexual assertion, partner
      negotiation, and communication skills), technical skills (condom use), and
      problem-solving training. Before and after the intervention, subjects completed
      measures of AIDS risk knowledge, health locus of control, social support,
      attitudes toward HIV prevention, attitudes toward condoms, self-efficacy, and
      perceptions of risk in addition to role-play assessments of behavioral skill
      resisting high-risk coercions. Postintervention, subjects exhibited increased
      knowledge about HIV/AIDS, more favorable attitudes toward prevention, greater
      internal and lower external locus of control scores, more favorable attitudes
      toward condom use, increased self-efficacy, and greater recognition of HIV
      vulnerability. Following intervention, the percentage of participants reporting
      sexual activity in high-risk contexts decreased, substantiating the
      intervention's effectiveness. Self-report data were corroborated by sexually
      transmitted disease treatment records. This uncontrolled demonstration effort
      suggests that skills training based on cognitive-behavioral principles may be a
      promising intervention strategy to lower vulnerable adolescents' risk of HIV
      infection.

PMID- 7818979
TI  - Attitudes and practices of hemophilia care providers involved in HIV risk
      reduction counseling.
AB  - Hemophilia physicians, nurses, and social workers attending a national conference
      were asked to complete a questionnaire assessing their attitudes and practices
      regarding HIV risk-reduction counseling. All of the 150 respondents reported
      recommending the use of condoms to their clients, but only two-thirds felt
      comfortable demonstrating a condom, while fewer could explain condom choices or
      how to make safe sex more pleasurable. Less than half questioned their clients
      about history of STDs, sexual practices, or level of sexual satisfaction. Those
      who devoted 50 percent or more time to HIV risk-reduction efforts reported being
      more complete in their assessment and more comfortable in their counseling role.
      Providers claimed it would help if they had more time (84%) and better skills
      (64%, especially nurses) for this practice. Because HIV prevention services in
      hemophilia are delivered by a team, further studies are required to determine the
      aggregate impact of their intervention on the client.

PMID- 7818980
TI  - Evaluating multicultural approaches in HIV/AIDS educational material.
AB  - In recent years health educators have become more aware of the impact of culture
      on the success of health education programs. This awareness has prompted
      experimentation with the use of cultural elements in HIV prevention and education
      efforts. The literature on multicultural education offers little guidance to the
      health educator on how to evaluate the appropriate and effective use of
      culturally distinctive messages in educational materials. The authors describe
      common errors in the development, pedagogical approach, and design of printed HIV
      educational material and suggest a framework for evaluating the impact of
      cultural elements on HIV education programs. The guidelines help one determine
      how effectively language and visual images are used in a given material, as well
      as how clearly information is conveyed.

PMID- 7818981
TI  - Evaluation of a thicker condom for use as a prophylactic against HIV
      transmission.
AB  - In an evaluation of the breakage rate of a thicker condom when used for anal
      intercourse, one hundred and eight gay men volunteered to use condoms which were
      30% thicker than standard condoms. Of the 772 condoms used, 14 broke during anal
      sex, representing a breakage rate of 1.8%. When one subject was removed from the
      sample because of inappropriate use of the condom, the overall breakage rate was
      1.6%. This compares favorably with the breakage rates reported for condom use
      during anal sex in other investigations, and is similar to the breakage rate for
      condom use during vaginal intercourse.

PMID- 7818982
TI  - Seventh International Conference on AIDS Education. November 13-17, 1993,
      Chicago, Illinois.

PMID- 7818983
TI  - Inositol lipid cycle in the nucleus.

PMID- 7818984
TI  - Altered guanine nucleoside triphosphate binding to transducin by cholera toxin
      catalysed ADP-ribosylation.
AB  - The influence of cholera toxin (CTX)-catalysed ADP-ribosylation on binding of
      guanine nucleoside triphosphates to transducin was studied by measuring the
      binding of the GTP analogue, guanosine 5'-[gamma-thio]triphosphate (GTP[gamma
      S]), to illuminated bovine rod outer segment (ROS) membranes treated with or
      without CTX. Besides the well-documented inhibition of the transducin GTPase
      activity, CTX treatment inhibited binding of GTP[gamma S] to illuminated ROS
      membranes. This inhibition was due to an approximately two-fold lower apparent
      affinity for the nucleotide, while the density of binding sites was not altered.
      CTX decreased the association rate of GTP[gamma S] by a factor of about two.
      Competition experiments with GTP, guanosine 5'-[beta, gamma]iminotriphosphate or
      GDP showed that the apparent affinities for both guanine nucleoside
      triphosphates, but not for GDP, were lowered by about two-fold upon CTX
      treatment. In contrast to CTX, pertussis toxin treatment of ROS membranes reduced
      the density of binding sites available to GTP[gamma S], while the apparent
      affinity of the remaining sites was unchanged. It is concluded that ADP
      ribosylation of transducin by CTX not only inhibits its GTPase activity but also
      decreases the affinity for guanine nucleoside triphosphates, data which suggest
      that the arginine moiety modified by CTX is involved in both binding and
      hydrolysis of GTP.

PMID- 7818985
TI  - Cyclic AMP stimulates Ca2+ entry in rat hepatocytes by interacting with the
      plasma membrane carriers involved in receptor-mediated Ca2+ influx.
AB  - The regulation of Ca2+ influx in rat hepatocytes by glucagon and cyclic AMP
      (cAMP) was investigated. Exposing hepatocytes to glucagon resulted in an increase
      in the initial rate of Ca2+ entry. The concentrations of glucagon producing half
      maximal and maximal stimulation of Ca2+ entry were 10(-10) and 10(-8) M,
      respectively. A similar stimulation of Ca2+ influx was obtained in cells exposed
      to cAMP analogues or to forskolin. Exposing hepatocytes suspended in nominally
      Ca(2+)-free medium to glucagon for 3 min produced a 9% decrease in the size of
      the vasopressin-sensitive Ca2+ pool; in contrast, N6,2'-O-dibutyryladenosine
      3':5'-cyclic monophosphate (Bt2cAMP) slightly augmented the size of this pool.
      Glucagon and Bt2cAMP synergized the initial vasopressin-stimulated Ca2+ and Mn2+
      influx rates, but only moderately increased the initial rate of Ca2+ entry after
      thapsigargin addition. The glucagon- and Bt2cAMP-stimulated Ca2+ influx was
      inhibited by the same antagonists of the plasma membrane Ca2+ carriers that
      mediate Ca2+ entry during stimulation by vasopressin. Thus, cAMP does not
      stimulate Ca2+ entry through either a capacitative type of mechanism or inositol
      phosphate turnover. The authors' findings instead suggest that cAMP acts
      directly, or through protein kinase A on the same Ca2+ carriers that are
      activated by phospholipase C-linked receptor agonists.

PMID- 7818986
TI  - KP-10, a novel protein kinase C substrate in intact mouse epidermal cells, is
      phosphorylated by novel protein kinase C eta and/or zeta.
AB  - Recently this group found an endogenous substrate protein for Ca(2+)-independent
      novel protein kinase C (nPKC), i.e. KP-10 (pI 4.7/25,500 M(r)), in primary
      cultured mouse epidermal cells [Nishikawa, K. et al. (1992) Cell. Signal. 4, 757
      776]. In the present study, the nPKC isozymes which phosphorylate KP-10 in these
      cells were determined. Western blot analysis revealed that PKC alpha, eta and
      zeta were present in epidermal cell 105,000 g supernatants and that the content
      of PKC zeta was much higher than those of PKC alpha and eta. Neither PKC beta,
      delta nor epsilon was detected in the 105,000 g supernatants. Phosphatidylserine
      and phorbol 12-myristate 13-acetate (PMA)-dependent KP-10 phosphorylating
      activity was immunoprecipitated by anti-PKC eta and zeta antibodies, but not by
      antiPKC alpha antibody. These results suggest that PKC eta and/or zeta
      phosphorylate KP-10 and play pivotal roles in intracellular signal pathways in
      intact epidermal cells.

PMID- 7818987
TI  - Forskolin mimics TSH action on the expression of protein kinase C isozymes in pig
      thyroid cell cultures.
AB  - In porcine thyroid cell cultures, phospholipid-dependent protein kinases (PKCs)
      have the same characteristics as intact glands. The overall PKC activity,
      presence of PKC isozymes, chromatographic pattern and endogenous substrates
      specificity were not modified during the two-day culture period. Three PKC
      isozymes (cPKC epsilon, nPKC epsilon and aPKC zeta) were identified by immunoblot
      analysis in the two subcellular fractions: cytosol and particulate extract, both
      in intact glands and two-day-old cultures. In cells cultured for two days in the
      presence of TSH (0.1 mU/ml), the overall PKC activity was stimulated (ca. 200%)
      in the two compartments. This stimulation was parallel to the increase in protein
      expression of the three PKC isoforms (as demonstrated by immunoblot analysis) and
      was accompanied by a redistribution of cPKC alpha and nPKC epsilon toward the
      particulate fraction. In TSH-treated cells, hydroxyapatite chromatography of
      cytosolic PKC revealed an additional peak of PKC activity eluted at 195 mM
      potassium phosphate. Its elution molarity did not correspond to the molarity of
      any known PKC isozyme, and it did not cross-react with antibodies directed
      against cPKC isozymes--: alpha, beta, or gamma. When TSH was replaced by
      forskolin (10(-5) M), identical quantitative and qualitative modifications were
      obtained, suggesting that, in thyroid cells, the cyclic AMP-dependent regulatory
      cascade could be involved in the control of PKC isoforms expression by TSH.

PMID- 7818988
TI  - Erythropoietin stimulates glycosylphosphatidylinositol hydrolysis in rat
      erythroid progenitor cells and inositolphosphate glycan modulates their
      proliferation.
AB  - The involvement of a glycosylphosphatidylinositol/inositolphosphate glycan
      (GPI/IPG) system in the erythropoietin (Epo) signal transduction was
      investigated. Endogenous GPI was evidenced in extracts of normal Epo-responsive
      cells after incorporation of [3H]glucosamine, [3H]inositol and
      [32P]orthophosphate. Incubation of these cells with Epo produced a rapid and
      transient hydrolysis of GPI with parallel release of IPG. IPG production was Epo
      dose dependent and the maximal effect was obtained with the same concentration of
      Epo which gave the maximal mitogenic effect, i.e. 1 U/ml. The number and size of
      erythroid colonies (CFU-E) were increased by the addition of purified rat
      erythroid IPG to the culture medium, but not to the same extent as with a maximal
      Epo treatment. Exogenous IPG effect was dose dependent. In the presence of
      suboptimal Epo concentrations, IPG has been found to potentiate Epo-induced CFU-E
      growth. These results support the hypothesis that a GPI/IPG based signal
      transduction system may be involved in Epo-induced cell proliferation.

PMID- 7818989
TI  - Involvement of protein kinase C in 1,25(OH)2-vitamin D3 regulation of calcium
      uptake by cultured myocytes.
AB  - 1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] produces an acute stimulation of calcium
      influx in cultured chick embryo myocytes through activation of voltage-gated Ca2+
      channels and involvement of cyclic AMP-dependent protein kinase A (PKA). To
      investigate the participation of protein kinase C (PKC) in this hormone-induced
      response, calcium uptake was measured in myocytes treated with PKC activators 12
      O-tetradecanoyl phorbol 13-acetate (TPA, 50 nM) or 1,2-dioctanoyl-rac-glycerol
      (DOG, 50 microM). TPA and DOG decreased 45Ca2+ uptake 37% below control cultures.
      Contrarily, the PKC inhibitors H7 and staurosporine increase myocyte Ca2+ uptake
      51% and 54%, respectively. In addition, PKC activity was augmented in cytosol
      (39%) and membranes (31%) of myocytes after 5 min of treatment with 0.1 nM
      1,25(OH)2D3. Likewise, the hormone induced a fast biphasic formation of
      diacylglycerol, the natural PKC activator, peaking at 30 s (26%) and 3 min (39%).
      On the other hand, the stimulation of Ca2+ uptake induced by compound H7 as well
      as 1,25(OH)2D3 was completely abolished with a specific PKA inhibitor. H7 also
      produced an increase in cAMP levels (172%) and PKA activity (204%). These results
      suggest the participation of PKC in 1,25(OH)2D3 regulated calcium influx in heart
      cells and the operation of a cross-talk mechanism between the PKC and PKA
      pathways.

PMID- 7818990
TI  - Effects of ionizing radiation and caffeine treatment on cyclin dependent kinase
      complexes in V79 hamster cells.
AB  - Exponentially growing V79 Chinese hamster lung fibroblasts irradiated with 7 Gy X
      rays undergo cell cycle arrest in the S and G2 phases. These arrests are
      released, probably on completion of DNA repair. A premature release occurs after
      treatment of irradiated cells with caffeine. This release is accompanied by
      increased activity of the p34cdc2 serine/threonine protein kinase complex [Hain
      et al. (1993) Cancer Res. 53, 1507-1510]. We have investigated in V79 cells
      whether the association of p34cdc2 with its regulatory subunits cyclin A and B is
      affected by irradiation and subsequent caffeine treatment and found that this was
      not the case. The phosphorylation of p34cdc2 as assayed by mobility shift on SDS
      polyacrylamide gels was increased as early as 0.5 h after irradiation and
      decreased after subsequent caffeine treatment. A novel protein p40, detected with
      anti-PSTAIRE antibodies, appeared several fold more abundant than p34cdc2. Its
      phosphorylation state also changed after irradiation and after subsequent
      caffeine treatment.

PMID- 7818991
TI  - The effect of acetylcholine and serotonin on calcium transients and calcium
      currents in identified Helix pomatia L. neurons.
AB  - The results presented demonstrate that in D neurons of the snail Helix pomatia
      L., acetylcholine (ACh) (10 divided by 100 microM) and serotonin (5-HT) (0.1
      divided by 1000 microM) applications reduce both the basal intracellular
      concentration level ([Ca2+]in) and the amplitudes of calcium transients induced
      by membrane depolarization. It is likely that the mechanism of [Ca2+]in changes
      in the suppression of calcium inward currents (ICa). Influences of Ach and 5-HT
      on ICa were studied. Both effects were dose-dependent (ACh--0.01 divided by 100
      microM and 5-HT--0.1 divided by 1000 microM). The half-maximal effects (IC50)
      were evoked by ACh concentration of 0.15 microM and 5-HT--15 microM. Furthermore
      we have also shown that in some cells 5-HT could evoke a transient increase in
      ICa (IC50 = 2 microM). The effects of Ach and 5-HT were nonadditive--the
      subsequent application of ACh after 5-HT, and vice versa, produced no inhibitory
      effects. This may indicate that both substances act through a common intermediate
      (possibly, G-protein).

PMID- 7818992
TI  - Effect of carbon tetrachloride on inositol 1,4,5-trisphosphate dependent and
      independent regulation of rat brain microsomal Ca2+ flux.
AB  - Carbon tetrachloride (CCl4) is a highly toxic industrial solvent with pronounced
      effects on the liver and brain. CCl4 is enzymatically cleaved to produce free
      radicals which attack membrane components, including proteins. Earlier reports
      indicated that CCl4 affects Ca(2+)-regulated events in the brain. Hence, the
      present study was initiated to determine whether CCl4 affects inositol 1,4,5
      trisphosphate (IP3) receptor binding, free-Ca2+ movements across the microsomal
      membrane and protein kinase C (PKC) activity in rat brain, since IP3, Ca2+ and
      PKC are known to be involved in signal transduction. [3H]IP3 binding, free-Ca2+
      movements and 45Ca2+ uptake were determined using rat brain microsomes and PKC
      activity was determined in the cytosolic fraction. CCl4 in vitro decreased
      [3H]IP3 binding to microsomes. IP3 mediated Ca2+ release from microsomes was
      inhibited and also the reuptake of IP3-released Ca2+ into microsomes was
      decreased in the presence of CCl4. CCl4 at concentrations < 2 microM
      independently released Ca2+ from microsomes. Uptake of total Ca2+ into microsomes
      was inhibited by CCl4 as observed with 45Ca(2+)-uptake studies. CCl4 at 1 microM
      inhibited PKC activity by 50%. Thus, perturbations in the binding of IP3 to its
      receptor sites, changes in the Ca2+ flux across the microsomal membrane and
      modulation of PKC activity by CCl4 in vitro suggested that CCl4 may exert
      neurotoxicity by altering signal transduction pathways.

PMID- 7818993
TI  - Effect of prenylcysteine analogues on chemoattractant receptor-mediated G protein
      activation.
AB  - The hypothesis that carboxylmethylation of gamma subunits plays a role in G
      protein activation was tested by examining the ability of N-acetyl-S-farnesyl-L
      cysteine (AFC) and its methyl ester (AFC-ME) to inhibit G protein-mediated
      signalling in intact HL-60 granulocytes and isolated HL-60 plasma membranes.
      Incubation of HL-60 granulocytes with AFC or AFC-ME inhibited superoxide release
      stimulated by fMet-Leu-Phe, but not by opsonized bacteria. AFC-ME, but not AFC,
      inhibited NaF- and PMA-stimulated superoxide release. Addition of AFC to HL-60
      membranes inhibited fMet-Leu-Phe-, leukotriene B4- (LTB4) and C5a-stimulated GTP
      gamma S binding and GTP hydrolysis more potently than it inhibited basal guanine
      nucleotide exchange. AFC-ME inhibited basal- and ligand-stimulated G protein
      activation with equal potency, but less potently than AFC. AFC also inhibited
      mastoparan-stimulated GTP gamma S binding. Binding of fMet-Leu-Phe and LTB4 to HL
      60 membranes was completely inhibited by AFC, while AFC-ME inhibited ligand
      binding by less than 50%. Neither AFC nor AFC-ME inhibited pertussis toxin or
      cholera toxin-catalysed ADP-ribosylation of alpha i. It was concluded that AFC
      interrupts signal propagation in G protein-dependent pathways by multiple
      mechanisms, including inhibition of ligand-receptor interactions, of receptor-G
      protein coupling and of guanine nucleotide binding to G proteins.
      Carboxylmethylation alters the specificity of AFC interruption of signal
      propagation in intact cells and isolated membranes.

PMID- 7818995
TI  - What is the significance of the ratio of the plasma urea to the plasma
      creatinine?

PMID- 7818994
TI  - Glycosaminoglycans in urine and amniotic fluid in congenital nephrotic syndrome
      of the Finnish type.
AB  - The heparan sulphate proteoglycan (HSPG) of the glomerular basement membrane
      (GBM) is considered to be mainly responsible for the charge selectivity of the
      GBM; decreased HSPG results in a decreased anionic charge of the GBM with
      increased heparan sulphate (HS) in the urine and is believed to be responsible
      for the proteinuria of the congenital nephrotic syndromes (CNS). Urinary HS and
      chondroitin sulphate (CS) concentrations in children with CNS of the Finnish type
      (CNF) and the total glycosaminoglycans (GAG) in amniotic fluid of CNF pregnancies
      were measured by three methods: Alcian blue, Safranine O and uronic acid assays.
      The total urinary GAG in CNF and other nephrotic patients was comparable to
      controls with all three methods. Urinary CS and HS in CNF did not differ
      significantly from controls. Total amniotic fluid GAG was also similar in CNF and
      control pregnancies. These results suggest some pathogenetic mechanism other than
      loss of glomerular HS chains in urine for the proteinuria of CNF.

PMID- 7818997
TI  - Haemorrhagic fever with renal syndrome in Korean children. Korean Society of
      Pediatric Nephrology.
AB  - Haemorrhagic fever with renal syndrome (HFRS) is an acute disease caused by
      Hantavirus and clinically characterised by abrupt onset of fever, various
      haemorrhagic manifestations and transient renal and hepatic dysfunction. We
      retrospectively reviewed 63 cases of HFRS in children from 13 different hospitals
      in Korea who presented over a 15-year period. The age of the patients ranged from
      7 to 15 years, with a male to female ratio of 8 to 1. Fifty-four (86%) patients
      were 10 years or older. On admission, 24 (38%) were in the febrile phase and 35
      (56%) were in the oliguric phase. Fever (100%) abdominal pain (91%), headache
      (76%) and vomiting (73%) were the most common symptoms. Backache, subconjunctival
      haemorrhage and hypertension were also noted in about one-third of patients.
      Hypotension was documented in only 7 (11%) patients. Leucocytosis (> 10,000/mm3)
      and thrombocytopenia (< 150,000/mm3) were noted in more than two-thirds of
      patients. Elevated blood urea nitrogen and serum creatinine was observed in 94%
      by the 7th (median) day of illness. Elevated aspartate aminotransferase and/or
      alanine aminotransferase were found in more than two-thirds of patients. Renal
      biopsy was performed in 12 patients and revealed various stages of acute tubular
      necrosis with occasional interstitial cell infiltration and oedema. Only 2 showed
      evidence of interstitial haemorrhage. Eleven patients required 1-3 days of
      dialysis and the remaining patients required only conservative management. Three
      (5%) patients died of shock, respiratory failure and pulmonary haemorrhage. All
      other patients recovered without sequelae. Although childhood cases were much
      less common than adults, clinical and laboratory findings were in general similar
      between children and adults.

PMID- 7818996
TI  - Acute tumour lysis syndrome with no evidence of tumour load.
AB  - Acute tumour lysis syndrome (ATLS) is a well-recognised complication of the
      treatment of a variety of malignant disorders in which a large mass of disease is
      obvious. ATLS may, however, occur even in the absence of bulk disease. We present
      two cases which, together with a review of previously reported cases, suggest
      that a cause of this rare phenomenon is primary renal lymphoma which subsequently
      develops into the leukaemic phase. This is supported by the observation that some
      bone marrow aspirates which are normal at the time of ATLS have shortly
      afterwards demonstrated lymphoblasts. Renal biopsy may not exclude primary
      lymphoma of the kidney. In excluding lymphoproliferative disease in the
      differential diagnosis of acute hyperuricaemia, the importance not only of bone
      marrow examination but of exhaustive investigation of the kidneys is stressed.

PMID- 7818998
TI  - What are the clinical uses of insulin-like growth factor-I in acute and chronic
      renal failure?

PMID- 7818999
TI  - Racial incidence of hemolytic uremic syndrome.
AB  - Hemolytic uremic syndrome (HUS) is the most common cause of acute renal failure
      in children and is caused by infection with verotoxin-producing Escherichia coli.
      There is no consensus on the relative incidence of HUS in blacks and whites. An
      equal racial incidence has been reported by two centers with small black
      populations. A series from Washington D.C. reported a low incidence in blacks.
      The population of Alabama is 32% black and 66% white. The Children's Hospital of
      Alabama admission rate has a similar racial distribution (35% black, 65% white).
      A record review from 1980-1992 identified 45 patients with HUS; 43 (96%) were
      white and only 2 (4%) were black. Based on census data for Alabama in 1980 and
      1990, this gives an average annual incidence of HUS of 0.45 per 100,000 in whites
      and of 0.043 per 100,000 in blacks (P < 0.001, Fischer's exact test). Similar
      results were found in the group of patients with HUS and a history of diarrhea;
      whites 0.39 and blacks 0.02 (P < 0.001). However, in those with no history of
      diarrhea there was no significant racial difference: whites 0.05 and blacks 0.02.
      There were too few blacks to compare clinical course and outcome. We conclude
      that typical diarrhea-associated HUS is a relatively rare disease in blacks
      compared with whites. The reasons are unclear.

PMID- 7819000
TI  - Effects of experimental ureteral obstruction on platelet-derived growth factor-A
      and type I procollagen expression in fetal metanephric kidneys.
AB  - Complete ureteral obstruction in fetal opossum kidneys has been used as an
      experimental method to induce tubulointerstitial damage and interstitial
      fibrosis. However, the molecular events underlying extracellular matrix
      deposition are currently unknown. Cytokines such as platelet-derived growth
      factor (PDGF) are considered possible participants in these processes. In this
      study we used a marsupial model of ureteral obstruction to examine the expression
      of PDGF-A and type I procollagen mRNAs by in situ hybridization. Complete
      unilateral ureteral obstruction was performed in six animals at midtrimester
      human equivalent. Obstructed kidneys, as well as the contralateral and age
      matched sham kidneys, were harvested at 1, 3, 5, 10, and 20 days post
      obstruction. Morphological assessment of the obstructed kidneys harvested between
      1 and 5 days post obstruction showed mild tubulocystic changes, interstitial
      fibrosis, and inflammation compared with controls. Kidneys harvested at days 10
      and 20 showed moderate tubulointerstitial damage compared with kidneys harvested
      after 1 and 5 days. PDGF-A mRNA signal of low abundance was detected within renal
      interstitial cells, urothelial cells of the pelvis, and focally within epithelial
      cells of immature distal convoluted tubules in non-obstructed kidneys. Type I
      procollagen mRNA expression was spatially co-distributed with PDGF-A-expressing
      interstitial cells. PDGF-A and type I procollagen signal intensities in
      obstructed kidneys harvested 10 and 20 days post obstruction were increased
      several fold compared with controls and kidneys harvested 1-5 days post
      obstruction. Both PDGF-A and type I procollagen mRNA increases correlated with
      morphological features of tubulointerstitial damage. Our results suggest that
      PDGF-A may participate in this form of fetal kidney damage.

PMID- 7819002
TI  - Effect of cyclosporine A on long-term allograft function in pediatric renal
      transplant recipients.
AB  - There have been concerns regarding long-term adverse effects of cyclosporine A
      (CSA) on renal allograft function. In a retrospective study, we compared long
      term allograft function up to 70 months after renal transplantation in pediatric
      recipients treated with and without CSA, using iothalamate clearance to assess
      glomerular filtration rate. Patients received CSA, prednisone, and azathioprine
      (CSA group, n = 16) or prednisone and azathioprine alone (Pred/AZA, n = 11). At
      48 months post transplant, the iothalamate clearances (mean +/- SD) were 57.9 +/-
      26.8 ml/min per 1.73 m2 in the CSA group and 68.5 +/- 20.2 in the Pred/AZA group
      (P > 0.05). The mean of the slopes of individual iothalamate clearances versus
      time during the first 70 months following transplantation were -0.156 in the CSA
      group and 0.095 in the Pred/AZA group. Neither slope was statistically different
      from zero. These data suggest that allograft function is not significantly
      depressed by CSA at 48 months post transplantation and that there is no greater
      rate of decline in allograft function up to 70 months post transplantation in
      patients receiving CSA when compared with the AZA/Pred group.

PMID- 7819001
TI  - Serum intact parathyroid hormone and ionised calcium concentration in children
      with renal insufficiency.
AB  - We report our experience of the use of an immunoradiometric assay for intact
      parathyroid hormone (i-PTH) and the measurement of plasma ionised calcium
      concentration (PCa2+) in 73 children with chronic renal insufficiency (CRI);
      plasma creatinine concentration (PCr) 52-856 mumol/l. There was a poor
      correlation between i-PTH and PCr (r = 0.10, n = 552) compared with that for C
      terminal PTH and PCr (r = 0.60, n = 248), suggesting that the i-PTH assay is
      independent of renal function in this group of treated children. A clear response
      of i-PTH to a low total plasma Ca (tPCa) and PCa2+ was observed. There was a
      significant positive correlation between both tPCa and PCa2+ (r = 0.50, n = 389)
      and the fraction of Ca2+ (the fraction of tCa which was ionised) and PCa2+ (r =
      0.50, n = 389). The finding of a low or normal PCa2+ with a low calculated
      fraction of Ca2+ was frequently observed, i.e. the measured tPCa was unexpectedly
      high, suggesting complexing of Ca2+ by accumulated anions in CRI. There was a
      poor relationship between the plasma albumin concentration and both bound plus
      complexed Ca (tPCa minus PCa2+) and the fraction of Ca2+ (r = 0.15 and -0.17,
      respectively). The positive predictive value for a raised i-PTH of a tubular
      reabsorption of phosphate of less than 80% was 0.87, and of an alkaline
      phosphatase greater than 800 U/l was 0.37.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7819003
TI  - Analysis of hypertension in children post renal transplantation--a report of the
      North American Pediatric Renal Transplant Cooperative Study (NAPRTCS).
AB  - Hypertension is common in children after renal transplantation and is associated
      with multiple factors. Data regarding the prevalence of post-transplant
      hypertension and the relationship between immunosuppressive drugs and the
      persistence of hypertension in a large population of North American children have
      not been available. This study was designed by the North American Pediatric Renal
      Transplant Cooperative Study to evaluate in a large diverse multicenter
      population of children the prevalence of hypertension post transplantation, the
      type of antihypertensive medications used to treat this hypertension and to
      determine the relationship between the blood pressure control and the
      immunosuppressive therapy. Analysis of 277 patients showed the following: (1) 70%
      of recipients required antihypertensive medications 1 month post transplant
      compared with 48% pre transplant; the incidence decreased to 59% at 24 months;
      (2) the majority of children received multiple drug therapy to control blood
      pressure; (3) hypertension can be controlled effectively despite inherent
      etiological factors, such as allograft source, prior hypertension and
      immunosuppressive therapy.

PMID- 7819004
TI  - Reliability of haemodialysis urea kinetic modelling in children.
AB  - The reliability of urea kinetic modelling (UKM) in paediatric haemodialysis was
      tested by comparing results of the classic variable volume model (UKM3), a
      recently introduced two-sample modification of this (UKM2) and direct
      quantification by a partial dialysate collection method (PDC). Urea generation
      rate (G) was also found from a 1-week collection of dialysate and urine (OWC).
      Nine children aged 2-18 years and weighing 10.6-39.9 kg were examined over 1 week
      (25 treatments). UKM3 and UKM2 gave almost identical results, but deviated from
      PDC and OWC. The two indirect methods overestimated G by 24% and 18%. However,
      the correlations between the results were very high for all variables and all
      methods (r > or = 0.96). Repeating UKM3 and UKM2 mid-week for 5 consecutive
      weeks, the following coefficients of variation were found: for the normalised
      whole body urea clearance (Kt/V) 10% and 11%, respectively; for normalised
      protein catabolic rate 17% and 14%. It is concluded that all tested methods can
      be used, but each method requires its own reference interval. Results of UKM seem
      to vary somewhat more than in adults. This should be considered when assessing
      children by such methods.

PMID- 7819005
TI  - Residual renal function in children on haemodialysis and peritoneal dialysis
      therapy.
AB  - Residual renal function was studied in 28 haemodialysis (HD) and 31 peritoneal
      dialysis (PD) patients aged 1-20 years observed over 6-43 (median 19) months.
      After the start of dialysis urine volume (UV) decreased to 57%, 46% and 26% of
      initial mean values in HD patients after 6, 12 and 24 months, respectively. In PD
      patients the corresponding figures were 57%, 69% and 62%. Mean UV calculated from
      all individual mean UV measurements observed was higher in PD than HD patients
      (954 vs. 537 ml/m2 per 24 h, P < 0.01). A better conservation of diuresis in PD
      patients was also suggested by a significantly longer persistence of a UV greater
      than 500 ml/m2 per 24 h compared with HD patients. Cox proportional hazard
      analysis identified dialysis modality and pre-dialysis UV of less than 1,000
      ml/m2 per 24 h as the only significant risk factors for UV survival. However, the
      decline of UV per time was similar in both modes of treatment. No significant
      changes of glomerular filtration rate were observed during both HD and PD
      treatment.

PMID- 7819006
TI  - New familial nephropathy involving glomerular and tubular basement membranes.
AB  - We describe two siblings, an 8-year-old boy and a 9-year-old girl, with severe
      mental retardation, dwarfism, optic atrophy and nephropathy. Laboratory
      examination showed beta 2-microglobulinuria, decreased creatinine clearance,
      hypercholesterolaemia and elevated serum levels of muscle enzymes. Renal biopsy
      from one of the patients demonstrated characteristic ultrastructural changes
      involving both the glomerular and tubular basement membrane. This group of
      symptoms and laboratory findings is quite distinct and differs from those of
      other reported familial nephropathy syndromes. We conclude that this disorder may
      represent a new syndrome of autosomal recessive inheritance.

PMID- 7819007
TI  - An unusual skin lesion in a pediatric patient with Wegener's granulomatosis.
AB  - Cutaneous manifestations occur in a significant number of patients with Wegener's
      granulomatosis (WG); however, the presentation and histopathology of these
      lesions are highly variable and may present problems in diagnosis. We report the
      presentation of a single large skin lesion in a pediatric patient with a history
      of WG and the characterization of this lesion by magnetic resonance imaging (MRI)
      and histopathology. MRI was helpful in delineating the extent of the lesion,
      although a skin biopsy was necessary to confirm the diagnosis of the vasculitic
      nature of the lesion.

PMID- 7819008
TI  - Neonatal renal venous thrombosis--a case report describing serial sonographic
      changes.
AB  - Neonatal renal venous thrombosis (NRVT) is a serious complication of newborns.
      Ultrasound is most useful in detecting NRVT. However, there is no detailed
      description of the evolution of ultrasound finding in NRVT. Here we report a
      patient with NRVT with complete ultrasound follow-up. Perivascular streaks were
      first seen at 3 days of age with a diffusely enlarged and echogenic right kidney.
      Echolucency then gradually appeared over the medulla area with shrinking renal
      size. Concomitant loss of renal function was evidenced by dimercaptosuccinic acid
      scan. The kidney became contracted at the age of 1 year. Since the pathognomonic
      perivascular streaks were present for only a few days, early ultrasound scanning
      should be performed for every newborn suspected of having NRVT.

PMID- 7819009
TI  - Fetal renal maldevelopment with oligohydramnios following maternal use of
      piroxicam.
AB  - A female neonate, born by cesarean section at 37 weeks of gestation, presented
      with respiratory distress syndrome, right pneumothorax and anuria. A sonogram
      showed increased echogenicity, with neither hydronephrosis nor macroscopic cysts.
      Peritoneal dialysis was started on the 14th day because of renal insufficiency,
      but the newborn died on the 33rd day. Family history was unremarkable, except
      that the mother received piroxicam at about the 26th week of gestation. A
      sonogram at the 28th week showed oligohydramnios. Histopathological study of the
      kidneys revealed crowded glomeruli and only few differentiated proximal
      convoluted tubules in the inner cortex, abnormally differentiated microcystic
      tubules and microcystic glomeruli in the outer cortex. Periodic acid-Schiff
      staining showed only traces of brush border in the dilated tubules of the outer
      cortex. Immunoperoxidase staining for epithelial membrane antigen was positive in
      the luminal border of all tubules. Electron microscopy confirmed the presence of
      brush border remnants and other proximal tubular characteristics in some
      segments. The renal abnormality bears some similarities to that found in familiar
      renal tubular dysgenesis, but it fits better with those described after maternal
      use of angiotensin converting enzyme inhibitors and nonsteroidal anti
      inflammatory drugs. The lesion in this case appears to have resulted from fetal
      exposure to piroxicam. Recently, a second pregnancy ended in a completely normal
      female newborn.

PMID- 7819010
TI  - Renal cell carcinoma developing in the pediatric recipient of an adult cadaveric
      donor kidney.
AB  - Renal cell carcinoma is an uncommon renal tumor in children, comprising between
      1.8% and 6.3% of all malignant renal tumors of childhood (whereas renal cell
      carcinoma is the commonest renal tumor in adults). We describe a 15-year-old girl
      with chronic renal failure secondary to renal dysplasia and branchio-oto-renal
      syndrome, who received a cadaveric renal transplant at 8 years of age from a 25
      year-old male donor. She developed severe chronic rejection 4 years after the
      transplant. A transplant nephrectomy was performed because of persistent gross
      hematuria. Histopathology of this graft showed chronic severe rejection and
      papillary necrosis. A fortuitous finding was a 1.5-cm renal cell carcinoma at one
      of the poles. We suggest that tumors which occur more commonly in adults and less
      commonly in children must be considered in children receiving adult organ
      transplants.

PMID- 7819011
TI  - Management of fluid overload in infants by tidal peritoneal dialysis: is there a
      benefit compared with continuous cycling peritoneal dialysis?
AB  - Dialysed infants are sometimes characterized by a hyperpermeable peritoneal
      state. In this situation decreasing dwell time and/or increasing dialysate
      tonicity are usually proposed to achieve adequate ultrafiltration (UF). We have
      investigated UF capacity under different peritoneal dialysis modalities in three
      infants. UF was not obtained with isotonic continuous ambulatory peritoneal
      dialysis (CAPD), and was only achieved with short dwell times and hypertonic
      CAPD. For the prescription of automated peritoneal dialysis, a shorter dwell time
      of hourly sequences is needed, which consequently decreases the phosphate
      diffusion time. Continuous cycling peritoneal dialysis with sequences of 1 h
      allowed efficient UF [UF/glucose absorption (UF/G) 4.2 +/- 0.9] but the
      dialysate/plasma (D/P) phosphate ratio was low (0.47 +/- 0.12). In contrast,
      tidal peritoneal dialysis gave a better UF/G ratio (6.8 +/- 0.7) without a
      decrease in the D/P phosphate ratio (0.64 +/- 0.18).

PMID- 7819012
TI  - Neisseria sicca peritonitis in a patient maintained on chronic peritoneal
      dialysis.
AB  - Neisseria sicca, previously classified as a "nonpathogenic" organism, has now
      been recognized as a cause of many infections, including endocarditis and
      meningitis. However, it has not been reported as a cause of peritonitis. We
      present a case of documented N. sicca peritonitis immediately following an
      episode of Staphylococcus aureus peritonitis in a pediatric chronic peritoneal
      dialysis (CPD) patient. N. sicca should be considered as a possible pathogen in
      CPD-associated peritonitis.

PMID- 7819013
TI  - Treatment of hypertension in children.
AB  - This review summarizes the current approach to antihypertensive therapy in
      children. It focuses on newer drugs, taking into account changes in clinical
      practice that have occurred since publication of the second Task Force report.
      Non-pharmacological therapy, including weight reduction, exercise, and dietary
      intervention, has great potential for the effective reduction of blood pressure.
      It should be introduced not only in patients with "significant" hypertension, but
      also in the care of patients with high normal blood pressure and to complement
      drug therapy for patients with "severe" hypertension. The goal of
      antihypertensive drug therapy is reduction of blood pressure to a level below the
      95th percentile for age and sex. Attempts to rapidly achieve normal blood
      pressure immediately after starting therapy are contraindicated. The objective of
      emergency treatment is prevention of hypertension-related adverse events, and
      this usually requires only a modest reduction in blood pressure. Nifedipine has
      become the most commonly used drug for emergency treatment of asymptomatic
      children. Exceptionally severe elevations of blood pressure or the presence of
      symptoms should be treated with more potent intravenous drugs. The converting
      enzyme inhibitors and calcium channel blockers currently are the primary agents
      for chronic treatment of hypertension in children. Diuretics are usually reserved
      for hypertensive patients with renal disease. beta-Adrenergic blocking drugs also
      are effective but have a number of potential adverse effects. Prazosin generally
      is used as a second-line agent, if the above-noted drugs are ineffective.
      Although minoxidil is still one of the most effective antihypertensive agents,
      its associated adverse effects have limited its usefulness.

PMID- 7819015
TI  - Cell adhesion molecules: from kidney morphogenesis to allograft rejection.

PMID- 7819014
TI  - Viral hepatitis in children with renal disease.
AB  - Specific and sensitive diagnostic tests are now available to identify type A, B,
      C, D and E hepatitis. Hepatitis A and E which cause only acute, very rarely
      fulminant, hepatitis are spread largely by the faecal-oral route, having a brief
      viraemic phase. Hepatitis B, C and D which are transmitted parenterally and via
      secretions are often associated with chronic viraemia. Patients with chronic
      renal disease are at particular risk. Impaired immunity due to disease or drugs
      increases the propensity to develop a chronic carrier state which may progress to
      cirrhosis and hepatocellular carcinoma. Limited reports indicate that hepatitis C
      infection may cause cirrhosis more rapidly than hepatitis B. The emergence of
      mutants to both hepatitis B and C is a cause for concern. Treatment with
      interferon is of limited efficacy. Screening of blood products for viral markers
      and prudent handling of potentially infected materials to avoid contamination of
      damaged skin or mucous membrane are the best strategies to prevent infection.
      Hepatitis B vaccination of all newborns, young adolescents and those at risk is
      the most effective means of reducing the carrier frequency.

PMID- 7819018
TI  - Clinical quiz. Tumor lysis syndrome.

PMID- 7819016
TI  - Development biology of the renal kallikrein-kinin system.
AB  - Kinins are endothelium-dependent vasodilators and natriuretic paracrine peptides
      that participate in the regulation of blood pressure, renal hemodynamics and
      sodium excretion. Several lines of evidence suggest an important role for
      intrarenal kinins and their receptors in kidney growth and development. (1) The
      developing rat kidney expresses all the components of the tissue kallikrein-kinin
      system: tissue kallikrein, low molecular weight (LMW) kininogen, kininase II and
      kinin receptors. Also, the developing liver expresses high molecular weight and
      LMW kininogens. Thus, a complete kinin-generating system exists in the developing
      kidney. (2) Gene transcription, mRNA and protein abundance, and enzymatic
      activity of renal kallikrein are all markedly up-regulated during postnatal
      kidney growth, and a positive correlation exists between renal kallikrein
      synthesis and the maturational rise in renal blood flow. (3) Rat glomerular
      mesangial cells in culture express the kinin receptors and proliferate in
      response to bradykinin, suggesting that endogenous kinins and their receptors
      modulate glomerular growth. (4) The newborn period is characterized by an
      activation of kinin receptor gene expression, and chronic pharmacological
      blockade of kinin receptors suppresses DNA synthesis in the developing but not
      adult kidney. Collectively, these data provide the basis for the hypothesis that
      endogenous kinins and the kinin receptors play an important role in the
      developmental biology of the metanephric kidney.

PMID- 7819017
TI  - Proceedings of the American Society of Pediatric Nephrology 1993 Education
      Symposium, Washington, D.C., 4 May, 1993.

PMID- 7819019
TI  - Chronic peritoneal dialysis in a child with Down syndrome.

PMID- 7819020
TI  - Assessment and interpretation of the tubular threshold for phosphate in infants
      and children.

PMID- 7819021
TI  - Pediatric dialysis transplant registries.

PMID- 7819022
TI  - Epidemiological evidence for an infective basis in childhood leukaemia.

PMID- 7819023
TI  - Treatment of advanced pancreatic cancer with 5-fluorouracil, folinic acid and
      interferon alpha-2A: results of a phase II trial.
AB  - Interferon alpha-2a (IFN-alpha) and folinic acid (FA) have been shown to modulate
      the cytotoxic effects of 5-fluorouracil (5-FU) in the treatment of cancer. A
      phase II study was initiated to evaluate the effect of a combination of 5
      FU/FA/IFN-alpha in patients with advanced pancreatic cancer. Sixty previously
      untreated patients with advanced adenocarcinoma of the pancreas were treated with
      500 mg m-2 FU via an intravenous bolus 1 h after the initiation of a 2 h infusion
      of 500 mg m-2 FA. Before starting the FA infusion, 6 million units (MU) of IFN
      alpha was administered subcutaneously. The treatment was repeated once a week. Of
      57 evaluable patients, eight (14%) had a partial response (PR), eight (14%) a
      minor response (MR) and 28 (49%) no change of disease (NC). Thirteen patients
      (23%) had progressive disease (PD). The median survival time was 10 months for
      all patients, 22 months for patients with partial remission and 5 months for
      patients with progressive disease. Many patients with tumour-related pain whose
      tumours were affected in terms of PR, MR, NC were free of pain during treatment
      with this regimen (22/36 patients). The common toxicities observed were fever
      (56%), nausea (37%) and diarrhoea (33%). These data suggest that biochemical
      modulation of 5-FU with FA and IFN-alpha has some positive effects in the
      treatment of pancreatic cancer of moderate toxicity.

PMID- 7819024
TI  - Mitoxantrone in metastatic apudomas: a phase II study of the EORTC Gastro
      Intestinal Cancer Cooperative Group.
AB  - We performed a phase II study with mitoxantrone in patients with carcinoid
      tumours, islet cell tumours and medullary carcinomas of the thyroid. Thirty-five
      eligible patients received mitoxantrone 12 mg m-2 i.v. every 3 weeks. Among 18
      previously untreated patients, three responded (17%, 95% CI = 4-41%); no
      responses were achieved in 17 previously treated patients. Of the 21 patients who
      had carcinoid tumours, 11 were previously untreated and two achieved a response
      (18%, 95% CI = 2-52%). Overall response rate was 9% (95% CI = 2-23%). At a median
      follow-up of 43 months, median overall survival was 16 months. The median
      survival of 21 patients with a normal alkaline phosphatase was 29 months and 9
      months for 14 patients with elevated serum levels (P = 0.005). A similar
      observation was noticed for gamma-glutamyltransferase (P = 0.007). We concluded
      that mitoxantrone is not active in APUD tumours. Elevated alkaline phosphatase
      and gamma-glutamyltransferase are associated with a poor prognosis.

PMID- 7819026
TI  - Prognostic effect of timing of operation in relation to menstrual phase of breast
      cancer patient--fact or fallacy.
AB  - The effects of the timing of operation in relation to menstrual phase and hormone
      receptor protein positivity and concentration of the 5 year survival of 267
      premenopausal women with operable breast cancer were evaluated. The patients were
      treated in the Tampere University Hospital Area in 1980-87, and information about
      menstrual cycle was recorded before the operation. Patients operated on during
      the luteal phase (days 15-32) had a trend towards a better survival rate (80.4%)
      than those treated in the follicular phase (days 1-14) (75.9%), but the
      difference did not reach statistical significance (P = 0.079). There was a small
      difference in the positivity and concentration of hormone receptor proteins,
      depending on the phase of the menstrual cycle. A more sensitive analysis found a
      statistically significant linear association between survival and day since last
      menstrual period (LMP) which was not totally accounted for by the variation in
      hormone receptor levels during the menstrual cycle or other main prognostic
      factors (P = 0.018 by Cox's multivariate regression analysis when LMP was used as
      a continuous variable). One possible mechanism for the effect of timing can be
      that physiological changes related to different phases of menstrual cycle
      unfavourably affect the quality of diagnostic and/or treatment procedures.
      Variation in the lag between the diagnostic confirmation and the operation of the
      patient affects the evaluation of such an effect and may account for the
      inconsistent results reported so far.

PMID- 7819025
TI  - Multiple risk factors associated with arsenic-induced skin cancer: effects of
      chronic liver disease and malnutritional status.
AB  - In order to evaluate the prevalence and multiple risk factors of arsenic-induced
      skin cancer among residents in Taiwanese villages in which chronic arseniasis is
      hyperendemic, a total of 1571 subjects aged 30 or more years were recruited
      between September 1988 and March 1989. All of them were interviewed personally by
      a public health nurse using a structured questionnaire, and 1081 interviewed
      study subjects, including 468 men and 613 women, participated in physical
      examination, giving a participation rate of 68.8%. The overall prevalence of skin
      cancer was as high as 6.1%, showing an increase with age in both men and women.
      There was a significant dose-response relation between skin cancer prevalence and
      chronic arsenic exposure as indexed by duration of residence in the endemic area,
      duration of consumption of high-arsenic artesian well water, average arsenic
      exposure in parts per million (p.p.m.) and cumulative arsenic exposure in p.p.m.
      years. Chronic carriers of hepatitis B surface antigen with liver dysfunction had
      an increased prevalence of skin cancer. Undernourishment, indexed by a high
      consumption of dried sweet potato as a staple food, was also significantly
      associated with an increased prevalence of arsenic-induced skin cancer. All these
      risk factors remained statistically significant in the multiple logistic
      regression analysis. Consistent with animal experiments, the findings imply that
      liver function and nutritional status may affect the metabolism of inorganic
      arsenic and the development of subsequent skin cancers.

PMID- 7819027
TI  - Localised plasmacytomas in Taiwan: comparison between extramedullary plasmacytoma
      and solitary plasmacytoma of bone.
AB  - The clinical features and response to therapy of 32 Chinese patients with
      localised plasmacytoma are presented, and a comparison between extramedullary
      plasmacytoma (EMP) and solitary plasmacytoma of bone (SPB) is made. Twenty-two
      patients had SPB and ten had EMP, accounting for 9% of all of our plasma cell
      neoplasms. Both groups had a male predominance with a median age of 54 years for
      SPB and 63 years for EMP. The common sites of SPB included vertebral bodies (15)
      and the skull (4). Most EMPs occurred in the oronasopharynx (6) and paranasal
      sinuses (2). An M-protein was detected in eight patients with SPB and in six with
      EMP. Seventeen patients with SPB and seven with EMP received radiation therapy,
      and all achieved initial local control. The pattern of failure in 22 patients
      with SPB manifested as local recurrence in two, multiple bone metastases without
      bone marrow plasmacytosis in two, multiple EMP progression in two, and
      development of multiple myeloma (MM) in one. There were two local recurrences,
      one further solitary bone involvement and one MM conversion in the EMP group.
      Local recurrence or dissemination was associated with the appearance of M-protein
      or an increase in the M-protein level in both groups. There was no significant
      difference in M-protein status or incidence and patterns of failure between the
      two groups. Patients with EMP had a more favourable overall survival than those
      with SPB (P = 0.03). The 5 year disease-free survival rate was 79% for EMP and
      58% for SPB (P = 0.53). Patients aged less than 60 years had a better overall
      survival in the SPB group, but location of tumour, presence of M-protein,
      radiation dose and chemotherapy did not influence prognosis in either group. Our
      results indicate that adequate local therapy can result in long-term survival
      with a low frequency of MM progression for patients with localised plasmacytomas,
      and both EMP and SPB appear to be similar in terms of frequency and patterns of
      failure.

PMID- 7819028
TI  - Pharmacokinetics of doxorubicin co-administered with high-dose verapamil.
AB  - The potential for the modification of the pharmacokinetics of doxorubicin (DOX)
      concurrently administered with high-dose verapamil (VER) has been investigated in
      17 patients with advanced neoplasms refractory to drugs belonging to the
      multidrug resistance spectrum. Steady-state concentration of DOX, systemic
      clearance and urinary excretion were analysed. No significant difference was
      found between the kinetic parameters estimated for DOX at different levels of VER
      and those reported for doxorubicin as single agent. It can be concluded that VER
      does not appear to modify DOX kinetics.

PMID- 7819029
TI  - The use of colour-coded and spectral Doppler ultrasound in the differentiation of
      benign and malignant breast lesions.
AB  - The aim of this study was to evaluate the role of colour-coded and spectral
      Doppler sonography to predict the benign or malignant nature of breast lesions. A
      total of 112 women with mammographically suspicious breast lesions were
      investigated prior to surgery. Thirty-nine breast carcinomas and 73 benign
      lesions were evaluated for the resistance index, pulsatility index and the flow
      velocity. A resistance index of > or = 0.70 was characteristic of malignant
      tumours with a sensitivity of 82% and a specificity of 81%. The positive
      predictive value was 70% and the negative predictive value 89%. Doppler
      sonography offers one possible method for further investigation of patients with
      mammographic abnormalities.

PMID- 7819030
TI  - The prognostic significance of DNA flow cytometry in breast cancer: results from
      881 patients treated in a single centre.
AB  - In this single-centre study of 881 patients, S-phase fraction (SPF) was shown to
      be a significant prognostic marker in terms of overall survival (OS), relapse
      free survival (RFS) and survival after relapse (SAR). Further, SPF had
      independent prognostic significance when considering a range of other
      clinicopathological variables, namely tumour grade and stage, nodal status,
      patient age, tumour size, menstrual status and treatment details. For OS and RFS,
      SPF was the second strongest predictor of the clinical course of the disease
      after nodal status, and for SAR it was the strongest prognostic marker. SPF
      correlated positively with histological grade but was the stronger predictor of
      survival. The distribution of SPF values was markedly different for the two
      ploidy classes of tumour, with DNA aneuploid tumours having a significantly
      higher average SPF. However, SPF retained its independent prognostic ability when
      DNA diploid and aneuploid tumours were analysed separately, DNA ploidy itself
      also proved to be an independent prognostic marker but the survival difference
      between the two ploidy classes was much less than that seen for different levels
      of SPF. Tumours with several DNA aneuploid populations (multiploid tumours)
      tended to have a worse prognosis than other aneuploid tumours but this trend did
      not reach statistical significance. In this and other studies from this centre,
      SPF has proved to be a robust predictor of clinical outcome in carcinoma of the
      breast.

PMID- 7819031
TI  - Assessment of the new proliferation marker MIB1 in breast carcinoma using image
      analysis: associations with other prognostic factors and survival.
AB  - The 'growth fraction' of tumours can now be assessed on paraffin sections of
      tissues using the monoclonal antibody MIB1 by a microwave antigen retrieval
      technique. The MIB1 labelling index was studied using a CAS 200 image analyser in
      177 tumours from women with primary operable breast carcinoma in whom long-term
      follow-up data were known. Statistical analysis showed a strong association
      between the MIB1 labelling index and histological grade (P < 0.001), tumour size
      (P = 0.002), tumour type (P < 0.001) and also patient survival (P < 0.001). No
      association with lymph node stage (P = 0.974) or regional recurrence (P = 0.185),
      the presence or absence of distant metastases (P = 0.418), patient age (P =
      0.309), menopausal status (P = 0.181) or oestrogen receptor status (P = 0.401)
      was found in this group of patients. In multivariate analysis for survival, when
      histological grade, lymph node stage and tumour size were included as well as the
      MIB1 labelling index, each was found to be of independent significance. If
      histological grade was not included, MIB1 replaced it as the most important
      variable predicting for survival in this group of patients. The results suggest
      that the tumour growth fraction, as assessed by the MIB1 labelling index, is an
      important predictor of survival.

PMID- 7819032
TI  - Pathological and biological features of mammographically detected invasive breast
      carcinomas.
AB  - The pathological and biological features of a consecutive series of impalpable
      invasive breast carcinoma, detected by mammography in the prevalent round of the
      breast screening programme, have been compared with a clinically presenting group
      of carcinomas in age-matched patients. There was a significantly higher
      prevalence of tubular carcinomas as well-differentiated infiltrating ductal
      carcinomas in the mammographically detected group, and a lower prevalence of
      poorly differentiated infiltrating ductal carcinomas. Lymph node metastasis was
      found in 6.5% of the impalpable group compared with 53% of the clinical group.
      The prevalence of oestrogen receptor was much higher in the impalpable group
      (96%) than in the control group (67%), although there were no significant
      differences for progesterone receptor. The prevalence of pS2 was also much higher
      in the impalpable group, as was cathepsin D. This finding is surprising in view
      of the reported relationship between cathepsin D and poorer survival. p53 and c
      erb-2 proteins were detectable in fewer impalpable carcinomas. The mean MIBI (Ki
      67) index was lower in the impalpable group (11.6) than in the clinical group
      (15.25). Within the mammographically detected group there was a significant
      difference in the MIBI index between tubular carcinomas and the different grades
      of infiltrating ductal carcinomas, with a wide range in each category but no
      association with size. The impalpable carcinomas detected by mammography differ
      from clinically presenting carcinomas in many ways, raising the question of
      whether a proportion or all would progress (dedifferentiate) with time.

PMID- 7819033
TI  - Stromal cell cathepsin D expression and long-term survival in breast cancer.
AB  - Breast cancers with an increased level of cathepsin D in tumour tissue extract
      have been found to have poor prognosis, but studies performed with
      immunohistochemistry have produced variable results. We analysed 213 primary
      invasive breast cancers for cathepsin D expression from archival tissue with
      immunohistochemistry. The minimum follow-up of the patients still alive was 26
      years. Women with ductal cancer that lacked cathepsin D expression in stromal
      macrophage-like cells had a 75% 5 year and 55% 30 year survival rate as compared
      with only a 40% 5 year and 20% 30 year survival rate if stromal cells expressed
      cathepsin D (P = 0.0003), whereas cathepsin D expression of cancer cells was
      associated with neither survival nor the several prognostic factors investigated.
      Stromal cell cathepsin D was more often present in the ductal than in the lobular
      histological type (80% vs 54%, P = 0.002), and its expression was strongly
      associated particularly with a high cell proliferation rate. However, in a
      multivariate analysis stromal cell cathepsin D expression did not have
      independent influence on survival in the entire series. We conclude that high
      stromal cell cathepsin D expression is associated with a poor short- and long
      term outcome in breast cancer.

PMID- 7819034
TI  - E-cadherin expression in primary and metastatic thoracic neoplasms and in
      Barrett's oesophagus.
AB  - Reduced expression of E-cadherin, a Ca(2+)-dependent cell adhesion molecule
      present in normal epithelium, has been associated with invasive and metastatic
      cancer. Immunohistochemistry was used in examining the relationship between E
      cadherin expression and stage in 59 oesophageal and 52 lung cancers. Advanced
      stage oesophageal cancers were associated with both reduced and disorganised E
      cadherin expression (P < 0.01). Advanced-stage lung adenocarcinomas generally
      exhibited disorganised or reduced E-cadherin expression, but no statistical
      association between expression pattern and stage was found (P > 0.05). No
      differences in stage were seen between tumours with reduced or disorganised E
      cadherin expression. Altered E-cadherin expression was detected in dysplastic,
      non-invasive Barrett's oesophagus. Importantly, high-level E-cadherin expression
      was detected in 17 of 17 lymph nodes containing metastatic cancer. E-cadherin
      mRNA expression was decreased in tumours with reduced protein expression, but not
      in tumours with disorganised expression. Expression of alpha-catenin mRNA, an E
      cadherin-associated protein, was detected in tissues with altered E-cadherin
      protein expression. Reduced and disorganised expression of E-cadherin appear to
      be related to transcriptional and post-translational events respectively, and
      both appear to represent altered cell adhesion associated with invasion and
      metastasis in thoracic neoplasms.

PMID- 7819035
TI  - Prognostic models for subgroups of melanoma patients from the Scottish Melanoma
      Group database 1979-86, and their subsequent validation.
AB  - For the past 20 years thickness of the primary tumour has been accepted as the
      most important guide to prognosis for patients with primary cutaneous malignant
      melanoma. The changing epidemiology of melanoma with an increasing number of
      patients with thin tumours has necessitated a reappraisal of this, with
      particular reference to interactions among tumour thickness, the patients' sex
      and the presence or absence of ulceration of the primary tumour. All primary
      cutaneous malignant melanomas diagnosed in Scotland between 1979 and 1986 were
      used as the test group (1978 patients). The proportional hazards model was used
      on all potential risk factors in the database and their two-way interactions, and
      the resulting models based on stepwise procedures were subsequently validated on
      289 melanoma patients first diagnosed in 1987 in the same geographic area. Four
      distinct subgroups of males and females with ulcerated or non-ulcerated lesions
      were identified. For females with ulcerated lesions, tumour thickness, mitotic
      count and anatomical site of primary all gave valuable prognostic information,
      whereas for females with non-ulcerated lesions only tumour thickness was of
      prognostic value. For males with ulcerated lesions, level of invasion was the
      only prognostic guide, while for males with non-ulcerated lesions both tumour
      thickness and level of invasion contributed significantly to prediction of
      prognosis. Prognosis markedly different across subgroups of the melanoma
      population, even to the extent that essential prognostic factors are not the same
      in the distinct subgroups. Verification of these prognostic guides derived from
      1979-86 patients has been achieved for all patients diagnosed with melanoma in
      1987 from the same geographic area. These data will therefore be useful aids for
      clinicians managing patients.

PMID- 7819036
TI  - DNA ploidy and S-phase fraction as prognostic factors in patients with uveal
      melanomas.
AB  - In 96 patients with uveal malignant melanomas the tumours were investigated by
      DNA flow cytometry. Thirty-eight per cent of the melanomas were aneuploid. By
      univariate analysis significant correlations with survival were found for
      histological type, tumour size, DNA ploidy, evidence of 'blind eye' and S-phase
      fraction. By multivariate analysis, significant prognostic variables were found
      to be histological type (P = 0.0008), tumour size (P < 0.0001) and DNA ploidy (P
      = 0.0038). Evidence of 'blind eye' was not significantly correlated with survival
      after adjustments for the other variables mentioned above. The S-phase fraction
      could be estimated in all 60 diploid tumours and in 12 of 36 aneuploid melanomas.
      By univariate analysis this variable was found to be a significant prognostic
      factor, but did not remain so after adjustment for ploidy, histological type and
      tumor size. We further conclude that patients with small DNA diploid uveal
      melanomas of spindle cell type have a rather favourable prognosis.

PMID- 7819037
TI  - The effect of calcium supplements on rectal mucosal proliferation.
AB  - Seventy-nine patients with colorectal adenomata were randomised to receive
      calcium carbonate (3,000 mg) or placebo in a double-blind randomised trial to
      assess the short- and long-term effects on rectal mucosal proliferation measured
      by the in vitro metaphase arrest technique crypt cell production rate (CCPR).
      There was no significant difference in mean CCPR between the groups before
      treatment or after 3 or 12 months. In those patients randomised to calcium, CCPR
      fell at both 3 months [9.0 (2.8) cc c-1 h-1, t = 3.15, d.f = 76, P = 0.002] and
      12 months [9.2 (3.3) cc c-1 h-1 t = 2.7, d.f. = 74, P = 0.009] compared with
      pretreatment CCPR [12.2 (5.5) cc c-1 h-1]. We have demonstrated that calcium had
      no effect on mucosal proliferation compared with placebo. The results on adenoma
      formation are awaited.

PMID- 7819038
TI  - Correlation between sialyl Tn antigen and lymphatic metastasis in patients with
      Borrmann type IV gastric carcinoma.
AB  - The expression of sialyl Tn (STn) antigen in 180 patients with Borrmann type IV
      gastric carcinomas was examined immunohistochemically. The rate of positive STn
      staining was 32% (57/180) for the primary tumours, and this positive staining
      correlated well with tumour extension, lymph node metastasis (P < 0.05) and
      peritoneal dissemination (P < 0.01). One-third (5/15) of patients with positive
      STn-staining cancer cells had a high level of serum STn. Lesions with positive
      STn staining were related to a lower survival rate for the patients (P < 0.05).
      Proliferative activity of the tumour, as measured by proliferating nuclear
      antigen (PCNA) labelling percentage and argyrophilic nucleolar organiser region
      (AgNOR) count, was significantly higher (41.5 +/- 13.0%, 3.78 +/- 0.98) in the
      STn-positive group than in the STn-negative group (34.2 +/- 13.2%, 3.48 +/- 0.85)
      (P < 0.01, P < 0.05 respectively). Estimating STn antigen may be useful for
      predicting the likelihood of lymph node metastasis or peritoneal dissemination
      and the clinical prognosis for patients with Borrmann type IV gastric carcinoma.

PMID- 7819039
TI  - Prognostic value of epidermal growth factor-receptor, T138 and T43 expression in
      bladder cancer.
AB  - Tumour-associated markers defined by monoclonal antibodies have proven useful to
      phenotype bladder tumours. In order to evaluate the prognostic value of such
      markers, we performed an immunohistochemical study on 57 transitional cell
      carcinomas (23 infiltrative and 34 superficial tumours) and ten healthy bladders
      using monoclonal antibodies against the external domain of the epidermal growth
      factor receptor (EGFR) and against the tumour-associated antigens T43, 19A211 and
      T138. Immunohistochemistry was performed on frozen sections using a two-step
      alkaline phosphatase method. The staining pattern obtained with each antibody was
      analysed according to the TNM classification, and results were analysed according
      to the subsequent clinical course. 19A211 preferentially stained superficial
      tumours, and T43, T138 and EGFR preferentially stained invasive tumours. Three
      monoclonal antibodies appeared to have prognostic value, since progression rate
      survival was significantly (log-rank test) associated with their expression of
      EGFR (P = 0.017), T138 (P = 0.0009) and T43 (P = 0.031). T138 expression was
      found to have an independent significant prognostic value using a stepwise
      logistic regression. T138 antibody may add significant information to classical
      pathological parameters.

PMID- 7819040
TI  - p53 immunohistochemistry as an independent prognostic factor for superficial
      transitional cell carcinoma of the bladder.
AB  - Although patients with superficial bladder cancer (Ta, T1) have a generally good
      prognosis, those patients who develop muscle-invasive tumours or metastatic
      disease at recurrence do poorly clinically. In the current study 69 patients
      undergoing complete transurethral resection for superficial transitional cell
      cancer of the bladder were investigated for different clinical and biological
      characteristics as possible prognostic factors: age, sex, performance of
      instillation therapy and immunohistochemical determination of mutational
      inactivation of p53 tumour-suppressor gene (monoclonal antibody PAb 1801) as well
      as immunohistochemical determination of the proliferation rate by staining for
      PCNA (proliferating cell nuclear antigen) (monoclonal antibody PC 10). After a
      median follow-up of 45.8 months, 12 of 14 patients (85.7%) with more than 20% of
      cells positive for p53 had disease progression with muscle-invasive growth
      compared with only one of 55 patients (1.8%) negative for p53 (P < 0.01, chi 2
      test). During univariate analysis histological grade (G1 vs G2) (P = 0.0373),
      positivity for PCNA (> 60% of cells) (P = 0.0033) and positivity for p53 (P <
      0.001) were significant prognostic factors for disease progression (log-rank
      test), while during multivariate analysis only positivity for p53 was a
      significant predictor for relapse of bladder cancer (P = 0.0029) (multivariate
      Cox regression analysis). The immunohistochemical detection of mutations of the
      p53 gene has been demonstrated to be a reliable, easily performed and thereby
      widely available technique for the investigation of fresh-frozen or paraffin
      embedded tumour specimens. The results demonstrate the important role of the p53
      tumour-suppressor gene protein in the development and for the progression of
      bladder cancer. If the high prognostic value of p53 mutations in superficial
      bladder cancer is confirmed in larger prospective trials, more aggressive
      therapeutic strategies could be discussed for patients with p53 mutations in
      their tumour specimens.

PMID- 7819041
TI  - Human papillomavirus status in the prediction of high-grade cervical
      intraepithelial neoplasia in patients with persistent low-grade cervical
      cytological abnormalities.
AB  - The role of human papillomavirus (HPV) detection in the management of patients
      with persistent low-grade (mild dyskaryosis or less) cervical cytological
      abnormalities is unclear. We have analysed cytological material from 167 such
      patients both cytologically and by non-isotopic in situ hybridisation (NISH) for
      HPV 16, 18, 31 and 33 and consensus primer polymerase chain reaction (PCR)
      amplification followed by both generic and specific typing for these HPV types.
      Cervical intraepithelial neoplasia (CIN) 2 or 3 was present in 40 of 167 patients
      (23.9%), and the positive predictive values (PPVs) for the presence of CIN 2 or
      3, of moderate or severe dyskaryosis at repeat cytology and an HPV-positive NISH
      and generic PCR signal were 100%, 66% and 42% respectively. The corresponding
      sensitivities were 48%, 68% and 87%. Addition of cytology to molecular analysis
      improved both PPV and sensitivity, the best combination being NISH and
      cytopathology (PPV 71%, sensitivity 87%). These data demonstrate that the
      presence of CIN 2 or 3 in patients with mild cytological abnormalities can be
      predicted by molecular detection of HPV in some cases, particularly when combined
      with cytological analysis. However, the magnitude of this prediction is dependent
      on the population of patients studied, and the clinical role of this approach
      therefore remains to be defined.

PMID- 7819042
TI  - Bone marrow examination in newly diagnosed Hodgkin's disease: current practice in
      the United Kingdom.
AB  - In the UK Hodgkin's disease is usually treated by either clinical oncologists or
      haematologists. A national study of the performance of bone marrow examination in
      newly diagnosed Hodgkin's disease was undertaken to establish current practice. A
      total of 620 questionnaires were despatched, and replies were received from 60%
      of consultants (45% of clinical oncologists and 70% of haematologists). Bone
      marrow examination was performed in all new cases significantly more often by
      haematologists than by clinical oncologists (74% vs 40%, P < 0.001). Among
      haematologists, there was no correlation between the number of new patients seen
      annually and practice, however clinical oncologists were even less likely to
      perform routine bone marrow biopsies if they saw more than ten patients per year
      (P < 0.02). Where bone marrow examination was performed selectively, the most
      common criteria used were peripheral blood cytopenia and advanced-stage disease.
      These criteria were applied in the same way by both clinical oncologists and
      haematologists. Bone marrow biopsy, an invasive and often painful procedure, is
      currently performed more frequently in Hodgkin's disease than can be recommended
      on the basis of recent studies in the literature and associated guidelines. There
      is a significant difference in practice between clinical oncologists and
      haematologists, and this raises the wider issue of the influence of hospital
      specialisation on patient management.

PMID- 7819043
TI  - Expression of p53 in urothelial cell cultures from tumour-bearing and tumour-free
      patients.
AB  - An explant culture technique was used to culture normal urothelium from patients
      with muscle-invasive bladder cancer (transitional cell carcinoma, TCC) (n = 11)
      and from non-tumour-bearing patients (n = 60). Cell cultures were examined for
      expression of p53 using the monoclonal antibody p53-240. There was a
      statistically significant increase in p53 expression in normal urothelial cell
      cultures from patients with TCC (P < 0.0005). Normal urothelial cultures from
      patients with TCC also showed more rapid proliferation in vitro when compared
      with non-tumour-bearing patients (P < 0.0005). A subgroup of non-tumour-bearing
      patients (n = 14) showed > 5% of cells expressing p53. p53 expression in this
      subgroup was found to correlate with cell proliferation in vitro (r2 = 0.766).
      None of these urothelial specimens was observed to express p53 when paraffin
      embedded preparations were stained with p53-D07 antibody prior to culture. The
      rate of cellular proliferation in this subgroup did not differ from that of
      normal urothelium from TCC patients. Twenty-two paraffin-embedded, muscle
      invasive TCC specimens were also evaluated for p53 expression using p53-D07. The
      expression of p53 in these tumours did not differ from that observed in normal
      urothelial cell cultures from patients with TCC (P = 0.26). This study identifies
      an overexpression of p53 in normal urothelial cells from patients with TCC and in
      proliferating cultures from a significant subgroup of patients without malignant
      disease. Increased p53 expression in normal cultured urothelial cells from
      patients with bladder cancer implies a global change in the mechanisms
      controlling urothelial cell division. This may represent an early step in the
      pathway to carcinogenesis.

PMID- 7819044
TI  - Expression of transforming growth factor alpha, epidermal growth factor receptor
      and epidermal growth factor in precursor lesions to gastric carcinoma.
AB  - Epidermal growth factor (EGF), its related peptide transforming growth factor
      (TGF-alpha) and their common receptor (EGFR) have been implicated in the control
      of cell proliferation and differentiation in the gastrointestinal epithelium and
      may play an important role in gastric carcinogenesis. We compared the
      immunohistochemical expression and topographic distribution of these peptides
      using Western blot analysis in gastric carcinoma precursor lesions and in non
      cancer tissue. We observed: (i) increased and extended expression of TGF-alpha in
      normal mucosa and hyperplasia in carcinoma fields compared with non-cancer
      controls; (ii) increased expression of EGFR in intestinal metaplasia (IM) from
      carcinoma fields compared with controls; (iii) EGF expression was not detected in
      normal mucosa and only weakly in IM; (iv) coexpression of TGF-alpha/EGFR and
      EGF/EGFR was higher in intestinal metaplasia in carcinoma fields than in non
      cancer controls. We conclude that altered expression of TGF-alpha/EGFR is
      associated with morphological changes during gastric carcinogenesis. In this
      regard increased expression of TGF-alpha is a very early event which is
      subsequently followed by up-regulation of EGFR and this has important biological
      and clinical implications.

PMID- 7819045
TI  - O6-methylguanine-DNA methyltransferase activities in biopsies of human melanoma
      tumours.
AB  - Tumour samples obtained from one primary melanoma and several lymph node and skin
      metastases were analysed for O6-methylguanine-DNA methyltransferase (MGMT)
      activity. While lymph node and skin metastases had similar average MGMT activity,
      the variance was significantly higher in lymph node metastases. Variability in
      MGMT activity was frequently observed in different metastases in the same
      individual and to a lesser extent within metastases.

PMID- 7819046
TI  - Reduced topoisomerase II activity in multidrug-resistant human non-small cell
      lung cancer cell lines.
AB  - Multidrug-resistant (MDR) cell lines often have a compound phenotype, combining
      reduced drug accumulation with a decrease in topoisomerase II. We have analysed
      alterations in topoisomerase II in MDR derivatives of the human lung cancer cell
      line SW-1573. Selection with doxorubicin frequently resulted in reduced topo II
      alpha mRNA and protein levels, whereas clones selected with vincristine showed
      normal levels of topo II alpha. No alterations of topo II beta levels were
      detected. To determine the contribution of topo II alterations to drug
      resistance, topo II activity was analysed by the determination of DNA breaks
      induced by the topo II-inhibiting drug 4'-(9-acridinylamino)methane-sulphon-m
      anisidide (m-AMSA) in living cells, as m-AMSA is not affected by the drug efflux
      mechanism in the SW-1573 cells. The number of m-AMSA-induced DNA breaks
      correlated well (r = 0.96) with in vitro m-AMSA sensitivity. Drug sensitivity,
      however, did not always correlate with reduced topo II mRNA or protein levels. In
      one of the five doxorubicin-selected clones m-AMSA resistance and a reduction in
      m-AMSA-induced DNA breaks were found in the absence of reduced topo II protein
      levels. Therefore, we assume that post-translational modifications of topo II
      also contribute to drug resistance in SW-1573 cells. These results suggest that
      methods that detect quantitative as well as qualitative alterations of topo II
      should be used to predict the responsiveness of tumours to cytotoxic agents. The
      assay we used, which measures DNA breaks as an end point of topo II activity,
      could be a good candidate.

PMID- 7819047
TI  - Clomiphene citrate reduces procarbazine-induced sterility in a rat model.
AB  - Chemotherapy with the cytotoxic drug procarbazine (PCB) causes permanent
      infertility in most male patients. Since many patients treated with this
      cytotoxic drug are of reproductive age, it is important to develop a method to
      protect spermatogenesis and fertility. It has been hypothesised that
      'spermatogenic arrest' by pharmacological intervention may render the testes less
      susceptible to the effects of chemotherapy. The present study investigated
      whether recovery of fertility in a male rat model could be achieved by
      suppression of spermatogenesis with high doses of clomiphene citrate (CC) prior
      to PCB administration. It was demonstrated that young male rats treated with a
      combination of CC and PCB partially recovered spermatogenesis and achieved almost
      normal fertility. In contrast, animals treated with PCB alone exhibited abnormal
      spermatogenesis and remained infertile.

PMID- 7819048
TI  - Expression of a 95 kDa membrane protein is associated with low daunorubicin
      accumulation in leukaemic blast cells.
AB  - A 95 kDa membrane protein (P-95) has been previously noted to be overexpressed in
      a doxorubicin-resistant subline of the MCF-7 breast cancer line and in clinical
      samples obtained from patients with solid tumours refractory to doxorubicin. We
      performed Western blotting on blast cell lysates from adults with acute myeloid
      leukaemia, using antisera to P-95. Concomitant flow cytometric assays measured
      daunorubicin accumulation and retention. Blasts from 16/46 patient samples had
      detectable P-95 and had reduced accumulation of daunorubicin compared with the
      negative marrows. Experiments with the P-95 positive MCF-7 multidrug-resistant
      subline demonstrated decreased daunorubicin accumulation and retention relative
      to the sensitive parent line. AML blast cells positive for P-95 also demonstrated
      greater overall in vitro survival in the presence of daunorubicin relative to the
      P-95-negative samples. The expression of P-95 did not correlate with failure to
      achieve an initial complete remission with daunorubicin and cytarabine induction
      chemotherapy. We conclude that the P-95 protein may possess an efflux transporter
      function, and may represent another mechanism responsible for anthracycline
      resistance in acute myeloid leukaemia.

PMID- 7819049
TI  - Decreased expression of messenger RNAs encoding endothelin receptors and neutral
      endopeptidase 24.11 in endometrial cancer.
AB  - In this study, we used reverse transcriptase-polymerase chain reaction (RT-PCR)
      to compare the expression of mRNAs encoding endothelin-1 (ET-1), endothelin
      receptors type A (ETA-R) and type B (ETB-R) and ET-1-degrading enzyme neutral
      endopeptidase 24.11 (NEP) in 15 endometrial cancer tissues and 13 normal
      endometrial tissues. The relative levels of ET-1 mRNA in endometrial cancer
      tissues did not differ from those in normal endometrium. Both ETA-R and ETB-R
      mRNA levels were significantly lower in endometrial cancer tissue than in normal
      endometrium (P < 0.001). The complete lack of NEP mRNA in endometrial cancer
      tissues was in marked contrast to results from normal endometrium (P < 0.001). In
      conclusion, differential expression of mRNAs encoding ET-R and NEP in normal
      endometrium and endometrial cancer suggests that ET action is altered in
      endometrial cancer compared with normal endometrium.

PMID- 7819050
TI  - Alternative therapeutic options in patients with advanced gastrointestinal
      cancer.

PMID- 7819051
TI  - Oesophageal cancer and amplification of the human cyclin D gene CCND1/PRAD1.
AB  - The human CCND1/PRAD1 gene, located in the 11q13 chromosomal region, encodes a
      cyclin D protein with potential oncogenic capacity and is involved in several
      human malignancies. The amplification and expression status of CCND1 was
      investigated in a series of oesophageal tumours. CCND1 is amplified in 54% and
      overexpressed in 63% of the tumours of the squamous cell type.

PMID- 7819052
TI  - Significance of epidermal growth factor receptor and c-erbB-2 protein expression
      in transitional cell cancer of the upper urinary tract for tumour recurrence at
      the urinary bladder.
AB  - An immunohistochemical study of the expression of epidermal growth factor
      receptor (EGFR) and c-erbB-2 protein was performed in fresh-frozen sections from
      30 patients with transitional cell cancers (TCCs) of the upper urinary tract (15
      renal pelvic cancers, 15 ureteral cancers) who underwent total
      nephroureterectomy. We followed them and examined whether TCC appeared in the
      urinary bladder. The follow-up period ranged from 116 to 2348 days (mean 666
      days). The mean period until a secondary urinary bladder cancer appeared was 306
      days (116-829 days). Thirteen of those 30 TCCs (43.3%) showed increased
      expression of EGFR, and 11 TCCs (36.7%) showed increased expression of c-erbB-2.
      In 12 of 30 patients (40.0%), a secondary urinary bladder cancer appeared after
      surgery. In only one of the ten patients (10.0%) whose tumours did not exhibit
      increased expression of either of these receptors the tumour recurred in bladder.
      On the other hand, in 11 of 20 (55.0%) patients whose tumours had increased EGFR
      and/or c-erbB-2 expression, secondary urinary bladder cancers recurred after
      surgery (P < 0.05). Thus, the recurrence rate of TCCs with increased EGFR and/or
      c-erbB-2 expression was significantly higher than that of tumours showing no
      increased expression of these receptors (P < 0.01). These results suggest that
      the immunohistochemical detection of the expression of EGFR and c-erbB-2 in
      urothelial cancers of the upper urinary tract might be a useful method for
      determining the likelihood of secondary bladder cancer recurrences.

PMID- 7819053
TI  - Lymphomas with testicular localisation show a consistent BCL-2 expression without
      a translocation (14;18): a molecular and immunohistochemical study.
AB  - The presence of the BCL-2 protein was studied in nine non-Hodgkin's lymphomas
      with testicular localisation. A consistent presence of the BCL-2 protein was
      found. The chromosomal translocation (14;18) was seen neither by cytogenetic
      analysis (n = 4) nor by polymerase chain reaction amplification and Southern
      blotting (n = 9). Therefore, this translocation is not responsible for the
      presence of the BCL-2 protein in non-Hodgkin's lymphomas with testicular
      localisation. We suggest that the presence of the BCL-2 protein in these
      lymphomas is related to the differentiation stage of the B-lymphocytes or may
      play a role in the pathogenesis of these lymphomas. The consistent finding of the
      BCL-2 protein in lymphomas with testicular localisation may support the clinical
      observation that these lymphomas are a separate entity.

PMID- 7819054
TI  - Interleukin 2-induced increase of vascular permeability without decrease of the
      intravascular albumin pool.
AB  - Interleukin 2 (IL-2) exhibits anti-tumour activity. High-dose IL-2 regimens are
      limited by side-effects such as pulmonary oedema and a systemic vascular leak.
      The mechanisms by which IL-2 mediates transvascular fluid and protein losses in
      humans are largely unknown. We have, therefore, measured the transcapillary
      escape rate (TER) of albumin as a reflection of the vascular permeability by
      injecting [125I]albumin (5 microCi i.v.). In ten melanoma patients pretreated
      with interferon alpha (IFN-alpha) TER of albumin was measured before and after IL
      2 injections (1.5 x 10(6) Cetus-U. s.c. daily for 4 days). The TER of albumin
      increased from 9.4 +/- 2.7% h-1 before to 14.9 +/- 3.3% h-1 (P < 0.001) after IL
      2 injections and the absolute outflux of albumin (Jalb) from 159 +/- 28 mg kg-1 h
      1 to 261 +/- 44 mg kg-1 h-1 (P < 0.001), whereas the intravascular albumin pool
      remained stable (136 +/- 19 g vs 136 +/- 18 g). IL-2 and IL-6 were not detectable
      in the plasma prior to IL-2 injections and increased to 549 +/- 315 U ml-1 (P <
      0.001) and 7 +/- 6 pg ml-1 (P < 0.01), respectively, after IL-2 administration.
      In conclusion, IL-2 increases the vascular permeability in humans, without
      affecting the intravascular albumin pool. This suggests that mechanisms such as
      the lymphatic return can compensate for the severe transendothelial fluid/albumin
      losses.

PMID- 7819056
TI  - Analysis of the p53 gene in human choriocarcinoma cell lines.
AB  - In the present study, we analysed human choriocarcinoma cell lines for
      abnormalities in the tumour-suppressor gene p53 by Southern blotting, Northern
      blotting, non-radioisotopic single-stranded conformational polymorphism (SSCP)
      and complementary DNA sequencing. In all cell lines (Bewo, GCH-1, GCH-2, SCH,
      JAR, JEG-3, NUC-1 and HCCM-5), no p53 gene abnormality was detected by using
      Southern blotting. p53 mRNA of the expected size was detected in all cell lines
      tested by Northern blotting. SSCP analysis revealed abnormalities of p53 cDNA in
      the SCH cell line. Sequencing analysis of the entire coding region of the p53
      gene revealed that both alleles were expressed in the JEG-3 cell line, and one of
      the alleles contained a point mutation (G to T) in codon 167 (Gln to His). In the
      NUC-1 cell line both alleles were point mutated. One allele had a point mutation
      (A to T) that resulted in a codon 17 change (Glu to Asp), and another had a point
      mutation (A to T) that caused a codon 24 change (Lys to Asn). In the SCH cell
      line, AGG was inserted between codon 249 and 250; this insertion resulted in an
      abnormal structure of the p53 protein. In three out of eight human
      choriocarcinoma cell lines, a p53 gene abnormality was detected. Therefore our
      data demonstrate that p53 gene abnormalities are associated with choriocarcinoma
      cell lines.

PMID- 7819055
TI  - An overview of randomised controlled trials of adjuvant chemotherapy in head and
      neck cancer.
AB  - Meta-analysis of the published results from 54 randomised controlled trials of
      adjuvant chemotherapy in head and neck cancer suggests that chemotherapy might
      increase absolute survival by 6.5% (95% confidence interval 3.1-9.9%). The odds
      ratio in favour of chemotherapy is 1.37 (95% confidence interval 1.24-1.5).
      Single-agent chemotherapy given synchronously with radiotherapy increased
      survival by 12.1% (95% confidence interval 5-19%). The benefit from neoadjuvant
      chemotherapy was less: a rate difference of 3.7% (95% confidence interval 0.9
      6.5%). The results suggest that the investigation of optimal agents and
      scheduling for synchronous radiotherapy and chemotherapy might still be important
      in clinical trials in head and neck cancer.

PMID- 7819057
TI  - Ovarian metastases from primary gastrointestinal malignancies: the Royal Marsden
      Hospital experience and implications for adjuvant treatment.
AB  - We investigated the pattern and frequency of ovarian metastases in patients with
      primary gastrointestinal malignancies and evaluated the response to surgery,
      chemotherapy and in three cases radiotherapy. The literature reports that this
      group of patients have a poor prognosis, but no report has specifically addressed
      the response to chemotherapy. Using a database which is generated prospectively,
      we analysed 51 patients with primary gastrointestinal malignancies and ovarian
      metastases. All patients received chemotherapy but only 36 were evaluable for
      response; five had adjuvant treatment and ten had non-measurable disease.
      Seventeen patients had surgical oophorectomy and three patients received
      radiotherapy. The overall response rate to chemotherapy was 22%; eight partial
      responses and no complete responses. When stratified according to site of
      response, 11 (31%) patients had a partial response at sites of extraovarian
      metastases and only five (14%) had a partial response in the ovaries. Seven
      patients with primary colorectal cancer had a differential response in favour of
      extraovarian sites. The median survival was 9 months for the 51 patients. Three
      premenopausal women with resected gastric carcinoma received adjuvant
      chemotherapy and relapsed only in the ovaries. In primary colorectal tumours the
      response of ovarian metastases to chemotherapy is less than that for other sites.
      Therefore, the ovary may be a sanctuary site for metastases which has important
      implications for adjuvant chemotherapy in women. These women could be followed up
      regularly by transvaginal ultrasonography to detect such metastases at an early
      stage when they would be amenable to surgical resection. Surgery should be
      considered for selected patients who develop metachronous metastases, as patients
      may be rendered disease free for several months.

PMID- 7819059
TI  - Homologous blood transfusion: the risks and alternatives.

PMID- 7819058
TI  - A randomised trial of octreotide vs best supportive care only in advanced
      gastrointestinal cancer patients refractory to chemotherapy.
AB  - Octreotide, a somatostatin analogue, has been shown to inhibit the growth of
      gastrointestinal cancers in vitro and in vivo. To assess the anti-tumour effect
      of octreotide, we performed a randomised trial comparing octreotide with best
      supportive care in advanced gastrointestinal cancer patients refractory to
      chemotherapy. A total of 107 patients with advanced gastrointestinal cancer
      refractory to chemotherapy were randomised to receive octreotide at the dose of
      200 micrograms three times a day for 5 days a week, or the best supportive care
      only. The primary outcome variable was the survival duration. Response rate was
      an outcome variable of secondary importance. Fifty-five patients (15 stomach, 16
      pancreas, 24 colon-rectum) received octreotide, while 52 (14 stomach, 16
      pancreas, 22 colon-rectum) received the best supportive care. Patients treated
      with octreotide had a significant advantage in duration of survival with a median
      survival time of 20 weeks vs 11 in the control group (P < 0.0001). This advantage
      was present also considering the survival data for each tumour group. Twenty-five
      patients (45%) given octreotide showed stable disease vs only eight (15%) in the
      control group (P < 0.001). In conclusion, octreotide therapy seems to confer a
      survival benefit in advanced gastrointestinal cancer patients refractory to
      chemotherapy. Additional studies will be needed to confirm these results and to
      clarify other questions about dose and schedule of octreotide.

PMID- 7819060
TI  - The clinical value of detecting gene rearrangements in acute leukaemias.

PMID- 7819061
TI  - Interleukin-3 is an autocrine growth factor of human megakaryoblasts, the DAMI
      and MEG-01 cells.
AB  - Interleukin-3 (IL-3), a cytokine known to be produced by activated T lymphocytes,
      mast cells, eosinophils and neutrophils, is a potent stimulator of normal
      haemopoiesis, particularly megakaryocytopoiesis. However, it remains unknown
      whether leukaemic megakaryoblasts can produce IL-3 and whether IL-3 is involved
      in the pathological process of megakaryoblastic leukaemia. In this study, several
      human leukaemia cell lines with or without megakaryocytic features, the DAMI, MEG
      01, HEL, K562, HL-60 and U937, were chosen as the models. It was first
      demonstrated by reverse transcriptase-polymerase chain reaction (RT-PCR) and
      indirect immunofluorescence assay that IL-3 was expressed in DAMI and MEG-01
      cells, but not in other cell lines, although two erythroleukaemic cells, the HEL
      and K562, also possess some megakaryocytic features. Interestingly, the mRNA for
      IL-3 receptor was detected in nearly all the cell lines except K562 cells,
      suggesting that expression of IL-3 and its receptor may be dissociated in most of
      the cell lines and that co-expression of IL-3 and its receptor exists in
      megakaryoblastic cell lines, the DAMI and MEG-01. Of the cell lines which did not
      express IL-3 under unstimulated condition, only HEL cells were able to express IL
      3 mRNA after treatment with PMA for 72 h. Furthermore, the proliferation of DAMI
      and MEG-01 cells could be enhanced in the presence of IL-3 and suppressed by the
      anti-IL-3 antibody and the IL-3 antisense oligodexyonucleotides (ODNs). These
      findings indicate that IL-3, as an autocrine growth factor, is involved in the
      growth of some megakaryocytic leukaemia cell lines.

PMID- 7819062
TI  - Haemopoiesis of transplanted patients with autologous marrows assessed by long
      term marrow culture.
AB  - We assessed the effect of antitumoural therapy at intensive doses on the
      haemopoietic system using long-term marrow cultures (LTMC) established from 33
      patients (25 with haematological diseases and eight with solid tumours) after
      autologous bone marrow transplantation (ABMT). When compared to 42 pre-graft
      patients, a decreased CFU-GM production and a defect in stromal layer (SL)
      confluence were found after ABMT on day 90 but also on day 365. However, these
      abnormalities were observed only in patients with haematological diseases and no
      differences between pre-graft and post-graft results were found in patients with
      solid tumours. Among the patients with haematological diseases, on day 90 those
      with acute lymphoid leukaemias showed lower CFU-GM production whereas patients
      with non-Hodgkin's lymphomas developed more frequently subconfluent or confluent
      SL. Other factors studied such as sex, patient age, disease status, marrow
      purging and post-graft administration of growth factors did not appear to
      influence post-graft LTMC results. Multivariate analysis including all the
      patients has shown (a) that solid tumours were associated with higher CFU-GM
      production, and (b) that conditioning regimens with total body irradiation (TBI)
      or busulfan led more frequently to non-confluent SL. In conclusion, high-dose
      therapy followed by ABMT can induce a persistent impairment of the stem cell and
      stromal cell compartments, particularly in patients with haematological diseases
      conditioned with TBI, despite the absence of any alloimmune reaction and post
      graft immunosuppressive therapy.

PMID- 7819063
TI  - Impaired TCR signal transduction, but normal antigen presentation, in a patient
      with common variable immunodeficiency.
AB  - We describe a 27-year-old white man with common variable immunodeficiency (CVID)
      who has two healthy histoidentical brothers and one IgA-deficient sister who
      shares one HLA haplotype with the patient. T cells from the patient with CVID
      showed an impaired response to recall antigens (tetanus toxoid, E. coli), whereas
      his IgA-deficient sister and his two healthy histoidentical brothers responded
      normally. Cross-mixing experiments using isolated monocytes and T cells from the
      CVID patient and one histoidentical brother revealed that the patient's monocytes
      were fully functional in processing and presenting antigen to resting T cells of
      his brother, and provided normal accessory cell function for superantigen-induced
      activation of his brother's resting T cells. In contrast, the patient's T cells
      were unable to respond to antigen presented by the brother's monocytes and failed
      to respond with an increase in intracellular free Ca++ to stimulation with
      superantigen, which is known to bind to the TCR V beta-chain outside the antigen
      binding groove. However, stimulation with a combination of PMA and IM, directly
      activating protein kinase C and increasing intracellular free Ca++ by bypassing
      membrane receptors, induced normal Ca++ flux. These data indicate that the
      patient with CVID has a defect in TCR-mediated signalling at the level of the T
      cells which is not present in his histoidentical healthy brothers or in his
      haploidentical IgA-deficient sister.

PMID- 7819064
TI  - A novel mutation in the erythrocyte protein 4.2 gene of Japanese patients with
      hereditary spherocytosis (protein 4.2 Fukuoka).
AB  - Human erythrocyte protein 4.2 (band 4.2; pallidin) is a major membrane protein
      that comprises 5% of the total weight of the human erythrocyte membrane.
      Deficiencies of this protein have been observed in hereditary spherocytosis with
      anaemia, suggesting a role of protein 4.2 in erythrocyte stability and integrity.
      The molecular basis of this disorder remains unknown. As a first step in
      elucidating the pathogenesis of hereditary spherocytosis associated with protein
      4.2 deficiency, we cloned and sequenced the erythrocyte protein 4.2 gene from a
      normal Japanese person. We prepared sets of oligonucleotide primers for
      polymerase chain reaction (PCR) and determined nucleotide sequences of exons and
      exon-intron boundaries of the protein 4.2 gene from three unrelated Japanese
      patients with hereditary spherocytosis due to a complete defect of protein 4.2,
      using PCR-related techniques. Two patients were homozygous for a missense
      mutation in codon 142 with the Ala (GCT)-->Thr (ACT) amino acid substitution that
      has been reported previously (protein 4.2NIPPON), whereas one patient was
      compound heterozygous for the same missense mutation in codon 142 and a guanine
      adenine transition in codon 119 that changes the codon for Trp (TGG) to the
      termination codon (TGA) (protein 4.2Fukuoka). No additional mutation was
      identified in other exons of the protein 4.2 genes. Dot-blot hybridization with
      allele-specific oligonucleotide probes showed that homozygosity for the missense
      mutation in codon 142 and compound heterozygosity for the codon 142 and the codon
      119 mutations were related to protein 4.2 deficiency in the families. Although
      two alleles of missense mutation of the codon 142 were also detected in 100
      alleles of healthy Japanese, results obtained in this study indicate that the two
      mutations described above are closely related to the pathogenesis of hereditary
      spherocytosis due to protein 4.2 defect.

PMID- 7819065
TI  - A variant of spectrin low-expression allele alpha LELY carrying a hereditary
      elliptocytosis mutation in codon 28.
AB  - Allele alpha LELY is a low-expression allele of the erythroid spectrin alpha
      gene. It carries mutations in exon 40 (alpha V/41 polymorphism) and intron 45,
      respectively, and is associated with partial skipping of exon 46. The latter
      phenomenon is thought to impair the recruitment of alpha-chains by beta-chains,
      and would eventually account for the low-expression character. When it occurs in
      trans to an alpha-allele responsible for hereditary elliptocytosis (alpha HE
      allele; alpha HE/alpha LELY diplotype), allele alpha LELY enhances the severity
      of elliptocytosis. Because allele alpha LELY is widespread, we anticipated that
      it would occasionally carry HE determinants. These variants of allele alpha LELY
      will be designated alpha HE-LELY allele. The HE component was the known alpha 28
      Arg-->His mutation. This alpha HE-LELY allele was investigated within the alpha
      HE-LELY/alpha LELY diplotype, a diplotype not described before. Except for the
      neonatal period, the presentation was mild. In a consistent manner, the alpha
      LELY component in cis of the alpha HE mutation counteracted the like component in
      trans.

PMID- 7819066
TI  - RNA transcripts of the beta-thalassaemia allele IVS-2-654 C-->T: a small amount
      of normally processed beta-globin mRNA is still produced from the mutant gene.
AB  - IVS-2-654 C-->T is a common Chinese beta-thalassaemia mutation. Previous studies
      report that this mutation resulted in the formation of an abnormally spliced mRNA
      and the absence of detectable normal beta-globin mRNA, hence the mutation was
      considered to cause beta o-thalassaemia. We recently used the method of PCR
      amplified cDNA copies of circulating erythroid cell mRNA to analyse the mutant
      gene transcripts and found that this IVS-2-654 mutation does not abolish normal
      RNA processing entirely, but that a significant amount (over 15%) of normally
      processed beta-globin mRNA is produced. Microglobin chain biosynthetic analysis
      using the HPLC method showed that beta-globin chain was also present in the blood
      of patients with IVS-2-654 C-->T mutation. Accordingly, this mutant allele leads
      to a beta (+)-thalassaemia. Further, the methodology described in this paper
      provides a new approach towards the detection of RNA transcripts of beta
      thalassaemia alleles as well as the study of gene expression in beta-thalassaemia
      and other genetic diseases.

PMID- 7819067
TI  - In vivo metabolic studies of glucose, ATP and 2,3-DPG in beta-thalassaemia
      intermedia, heterozygous beta-thalassaemic and normal erythrocytes: 13C and 31P
      MRS studies.
AB  - 13C and 31P magnetic resonance spectroscopy was used to characterize the in vivo
      kinetics of glucose metabolism and intracellular ATP and 2,3-DPG concentrations
      in erythrocytes obtained from beta-thalassaemia intermedia, heterozygous beta
      thalassaemic and normal individuals and maintained in suspension. Except for an
      upfield chemical shift in the 2P and 3P resonance of 2,3-DPG in the thalassaemia
      intermedia erythrocytes, the 31P spectra were comparable between all three blood
      types, showing similar concentrations of ATP (from 4.5 to 5.2 mumol/g Hb) and 2,3
      DPG (from 17.2 to 19.7 mumol/g Hb). However, the profile of glucose metabolism
      was quite different in beta-thalassaemia intermedia erythrocytes, whereas glucose
      was consumed at a rate of 0.089 +/- 0.035 fmol/cell/h, significantly higher than
      that of normal (0.032 +/- 0.018 fmol/cell/h; P = 0.01) and heterozygous (0.025 +/
      0.004 fmol/cell/h; P = 0.01) erythrocytes. This near 3-fold faster rate of
      glucose metabolism in the thalassaemia intermedia erythrocytes could not be
      accounted for by any increase in glucose flux via the Embden-Meyerhof pathway,
      since no significant difference in 3-13C-lactate synthesis was observed among the
      three blood types (in units of fmol/cell/h, normal, 0.021 +/- 0.013;
      heterozygous, 0.021 +/- 0.006; beta-thalassaemia intermedia 0.045 +/- 0.025).
      These results reflect an accelerated rate of glucose metabolism in thalassaemia
      intermedia erythrocytes because the contribution of reticulocytes to this altered
      pattern of metabolism could be excluded. As the only other route of glucose
      metabolism in erythrocytes is the pentose phosphate pathway (PPP), these results
      indicate that the PPP is more active in beta-thalassaemia intermedia
      erythrocytes, perhaps as a consequence of their elevated intracellular oxidative
      state.

PMID- 7819068
TI  - Homozygous beta-thalassaemia resulting in the beta-thalassaemia carrier state
      phenotype.
AB  - This paper describes the phenotypic manifestations of a very mild beta
      thalassaemia mutation detected in several members of two families of Italian
      descent. The molecular defect, defined by denaturing gradient gel electrophoresis
      analysis and direct sequencing, consists of a C-->G substitution at position 844
      of IVSII of the beta-globin gene within the consensus sequence of the IVSII
      acceptor splice site. Heterozygotes for this mutation show a haematological
      phenotype ranging in severity from silent beta-thalassaemia to that of a mild
      beta-thalassaemia carrier state, whereas homozygotes have the typical
      manifestations commonly resulting from heterozygosity for a beta-thalassaemia
      mutation. Compound heterozygotes for the IVSII nt844 (C-->G) mutation and a
      severe beta-thalassaemia mutation have the phenotype of thalassaemia intermedia.
      This paper indicates that the presence of borderline red blood cell indices or
      HbA2 values should make one suspect the presence of a very mild or silent beta
      thalassaemia.

PMID- 7819069
TI  - Development of extended multidrug resistance in HL60 promyelocytic leukaemia
      cells.
AB  - In an attempt to mimic clinical conditions for the treatment of leukaemia, the
      HL60 promyelocytic cell line was treated for 18 h with low, clinically relevant,
      levels of the anthracycline epirubicin and the Vinca alkaloid vinblastine. The
      resulting drug-resistant sublines not only expressed P-glycoprotein and the MDR
      phenotype but were also cross-resistant to chlorambucil, methotrexate and
      cisplatinum, and had increased resistance to radiation. Development of resistance
      was associated with an aberrant differentiation phenotype with decreased
      expression of myeloid antigens and expression of glycophorin A, an antigen
      normally associated with erythroid differentiation. The ability of HL60 cells to
      terminally differentiate in response to all-trans-retinoic acid (vitamin A acid)
      was lost in the sublines. These results suggest that either a single novel
      mechanism is responsible for multiple drug resistance or the initial response to
      drug treatment is the co-induction of multiple mechanisms. These cells and the
      method by which they were generated therefore provide a clinically relevant model
      for the study of the initial events in the development of not only multidrug
      resistance but also the extended multiple drug resistance usually encountered in
      the treatment of leukaemia.

PMID- 7819070
TI  - Karyotypic and ras gene mutational analysis in idiopathic myelofibrosis.
AB  - Karyotypic analysis was performed in a total of 69 patients with well
      characterized idiopathic myelofibrosis. Karyotypic abnormalities were detected in
      46% of cases examined during the chronic phase (29/63); with three abnormalities,
      del(13q), del(20q) and partial trisomy 1q, accounting for 75% of all
      abnormalities at diagnosis. The absence of del(5q), trisomy 8 and 21, as well as
      the rarity of monosomy 7, contrasts with pooled published data and may reflect
      our exclusion of closely related disorders, in particular MDS with fibrosis.
      Chromosomal aberrations increased to approximately 90% (8/9) in patients analysed
      during acute transformation. Mutational activation of codons 12, 13 and 61 of N-,
      Ha- and Ki-ras genes were assessed by polymerase chain reaction and hybridization
      with synthetic non-radioactive digoxigenin-labelled probes. Three mutations were
      detected in samples of peripheral blood DNA taken from 50 patients during the
      chronic phase of their disease: one N12 Asp (GGT-->GAT) and two N12 Ser (GGT-
      >AGT) mutations. The results from this study indicate that karyotypic
      abnormalities are present in at least 29% of cases at diagnosis and that
      del(13q), del(20q) and partial trisomy 1q are the most frequent findings. Ras
      mutations were relatively infrequent (6%) and appeared restricted to the N-ras
      gene. Karyotypic analysis at diagnosis was found to be of prognostic
      significance.

PMID- 7819071
TI  - Purification and characterization of human platelet von Willebrand factor.
AB  - Platelet von Willebrand factor (vWf) was purified from human platelet
      concentrates. The multimeric structure of the purified platelet vWf was similar
      to that observed in the initial platelet lysate, and, like the platelet lysate,
      the purified platelet vWf contained higher molecular weight multimers than plasma
      vWf. The apparent molecular weight of the reduced platelet vWf subunit was
      similar to the plasma vWf subunit. The N-terminal amino acid of the purified
      platelet and plasma vWf was blocked. In concentration dependent binding to
      botrocetin- or ristocetin-stimulated platelets, 125I-plasma vWf bound with a
      higher affinity than platelet. The ristocetin cofactor activity per mg of
      purified plasma vWf was 5-fold greater than the platelet vWf activity. Platelet
      and plasma vWf bound to collagen with similar affinities; however, platelet vWf
      bound to thrombin-stimulated platelets and to heparin with a higher affinity than
      plasma vWf. The differences in the binding affinity(s) of plasma and platelet vWf
      to platelet GPIb and GPIIb/IIIa and extracellular matrix proteins may reflect
      different roles for plasma and platelet vWf in the initial stages of haemostasis
      and thrombosis.

PMID- 7819072
TI  - Factor VIII, ABO blood group and the incidence of ischaemic heart disease.
AB  - Relations of factor VIII activity, FVIIIC, and von Willebrand factor antigen
      (vWFAg), with ischaemic heart disease (IHD) were examined in 1393 men aged
      between 40 and 64 years at entry to the Northwick Park Heart Study (NPHS) who
      experienced 178 first major episodes of IHD during an average follow-up period of
      16.1 years. After allowing for the large factor VIII differences between the main
      ABO blood groups, FVIIIC was probably associated with IHD incidence, possibly
      more strongly with fatal than non-fatal episodes. Thus, an increase of 1 standard
      deviation in FVIIIC raised the risk of fatal IHD by about 28%. vWFAg was also
      significantly associated with fatal events. The observed relation of FVIIIC with
      IHD incidence probably underestimates the true strength of the association
      because of the considerable within-person and laboratory variability in factor
      VIII measurements. FVIIIC and vWFAg were strongly correlated (r = 0.57) and in
      statistical terms there may be little to choose between them in long-term studies
      of IHD. Taking account of evidence that haemophiliacs seem to experience less IHD
      than expected, high factor VIII levels may contribute to the incidence of IHD by
      increasing thrombogenic potential. The incidence of IHD was significantly higher
      in those of blood group AB than in those of groups O, A or B, particularly for
      fatal events. There was no evidence that the FVIIIC and vWFAg associations with
      IHD are determined by ABO group. The factor VIII and ABO blood group effects
      therefore appeared to be independent. Group AB may be a genetic marker of
      characteristics influencing other indices of IHD risk such as short stature, NPHS
      men (though not women) of group AB being about 2 cm shorter than those of other
      groups.

PMID- 7819073
TI  - Fraxiparin, a low-molecular-weight heparin, stimulates megakaryocytopoiesis in
      vitro and in vivo in mice.
AB  - The effect of a low-molecular-weight heparin, faxiparin (Nadroparin), on murine
      megakaryocytopoiesis in vitro and in vivo was studied in comparison with
      unfractionated heparin. The addition of fraxiparin at 1-20 IU/ml into plasma clot
      cultures but not serum-free agar culture significantly enhanced MK colony growth.
      Furthermore, fraxiparin was found to potentiate the stimulating activity of
      aplastic anaemia serum (AAS) but not stem cell factor (SCF), interleukin-3 (IL
      3), granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin
      (Epo), on MK colony growth in vitro, and to neutralize the inhibitory effect of
      platelet factor 4 (PF4) in vitro and in vivo. Fraxiparin also acted
      synergistically with heparin cofactor II and antithrombin III to promote
      megakaryocyte colony formation. Intraperitoneal administration of fraxiparin
      twice daily for 4 d at 0.1-25 IU/injection increased in mice the level of blood
      platelet counts and the number of single MKs and CFU-MK in bone marrow. These
      data demonstrate that fraxiparin is able to positively regulate
      megakaryocytopoiesis.

PMID- 7819074
TI  - Possible misdiagnosis using the Xba I polymorphism for prenatal diagnosis of
      haemophilia A.
AB  - A mother of two haemophilia A sons presented at 7 weeks pregnancy for a prenatal
      diagnosis. Southern blot analysis of haemophilia DNA at the factor VIII intron 22
      Xba I restriction fragment length polymorphism (RFLP) site revealed an Xba I
      haplotype of A-B+C-. This haplotype has been alluded to but not reported before,
      and when a 1.6 kb Bst XI fragment of p482.6 is used as a probe the resulting band
      pattern is similar to that of females heterozygous at site A.

PMID- 7819075
TI  - Reactivation of antibodies of donor and recipient origin to platelet antigens
      early after allogeneic bone marrow transplantation: a case report.
AB  - Reactivation of platelet-reactive antibodies of donor and recipient origin is
      described in a patient following allogeneic BMT (donor: anti-HPA-5b; recipient:
      anti-HLA, anti-HPA-1b). The antibodies were detected around day 15 after BMT,
      peaked around day 25, and then decreased. These antibodies are interpreted as an
      antigen-independent reactivation of secondary B-cell responses, activated in the
      context of recognition of host antigens by the graft.

PMID- 7819076
TI  - Treatment of chronic childhood immune thrombocytopenic purpura with intramuscular
      anti-D immunoglobulins.
AB  - Seven patients with chronic immune thrombocytopenic purpura (ITP) were treated
      with intramuscular anti-D (anti-D IgG) five times, on an alternate-day basis, or
      until a platelet count of 100 x 10(9)/l was achieved, and, subsequently, when
      necessary to maintain platelet counts above 50 x 10(9)/l. Five patients responded
      to therapy, two of whom entered long-term remission. Although signs of haemolysis
      were present in all patients, anaemia was never a problem. No patient developed
      haematomas at the site of injection. We suggest that intramuscular anti-D
      represents a safe and relatively inexpensive alternative to intravenous gamma
      globulins (IVGG) for children with severe chronic ITP.

PMID- 7819077
TI  - A spontaneous remission of lymphoid blast crisis in chronic myelogenous leukaemia
      following blood transfusion and infection.
AB  - We report a case of spontaneous remission of lymphoid blast crisis in chronic
      myelogenous leukaemia (CML) which returned to chronic phase, without the use of
      cytostatic chemotherapy, following an episode of viral infection and blood
      transfusion. Although complete remissions of acute leukaemia have been described,
      this evolution is extremely rare and has never been reported in CML blast crisis.
      The role of hypothetical factors leading to such a rare event are briefly
      discussed.

PMID- 7819078
TI  - Recombinant human erythropoietin may correct erythropoietin-deficient
      hyporegenerative anaemia in children given cardiac transplantation.
AB  - Cyclosporin-A reduces erythropoietin production and, together with the inhibitory
      effect of cytokines on erythropoiesis, may be potentially responsible for the
      anaemia observed in some patients after heart transplantation. Two children given
      cardiac transplantation and receiving cyclosporin-A developed transfusion
      dependent hyporegenerative anaemia. Erythropoietin production was inappropriately
      low for the degree of anaemia, with an observed/predicted log(serum EPO) ratio of
      0.54 and 0.49, respectively. The children were treated with rHuEPO at a dose of
      75 U/kg three times weekly for 1 month and then twice weekly via subcutaneous
      injection. No further transfusion was necessary and restoration of normal
      erythroid activity was obtained, with normal haemoglobin values. No adverse
      effects were observed. Our experience suggests that recombinant human
      erythropoietin may be useful in treating the anaemia associated with cardiac
      transplantation.

PMID- 7819079
TI  - Ultrasound examination of pathological cervical lymph nodes in patients with non
      Hodgkin's lymphoma and Hodgkin's disease.
AB  - The choice of treatment of malignant lymphoma may vary considerably and is mainly
      determined by the pathology and clinical stage. Ultrasonography is currently one
      of the most sensitive techniques for evaluation of the cervical area. We set out
      to assess the value of ultrasound imaging when added to conventional staging
      (physical examination, laryngoscopy, computer tomography of thorax and abdomen,
      bone marrow cytology and histology) of malignant lymphoma in 47 patients with
      untreated lymphoma. Hodgkin's disease was present in 14 patients and non
      Hodgkin's lymphoma in 33 individuals. The ultrasound results were independently
      compared with physical examination of the neck. Ultrasonography revealed
      additional pathological lymph nodes in 6/47 cases (13%). Furthermore, the
      diagnosis non-Hodgkin's lymphoma could be established in one patient merely as a
      result of ultrasonography. Ultrasonography of the neck may reveal more
      pathological lymph nodes in a significant number of patients and may be of value
      in the initial staging of patients with malignant lymphoma.

PMID- 7819080
TI  - A biclonal large granular lymphocyte (LGL)/NK-associated (NKa) disorder of CD4+
      and CD8+ lymphocyte subpopulations characterized by the simultaneous presence of
      distinct TCR rearrangements.
AB  - This communication reports a patient with concomitant expansions of CD4+ and CD8+
      large granular lymphocytes. Immunological analyses revealed that the abnormally
      increased CD4+ LGL fraction was phenotypically similar to other reported
      persistent CD4+ LGL expansions, whereas the phenotypic profile for the CD8+ LGL
      component was unusual. Of particular note was the finding that both the CD4+ and
      CD8+ LGL fractions showed high membrane CD45RO isoform expression, thus
      suggesting their 'primed' status. Molecular biology studies of immunomagnetically
      fractionated cells using a T gamma 9 TCR gamma gene primer further revealed that
      the CD4+ and CD8+ components were both clonal but showed different patterns of
      rearrangement. It is suggested that the simultaneous presence of CD4+ and CD8+
      clonal populations are unlikely to have been derived from a common progenitor and
      that they reflect expansions of functionally restricted subpopulations.

PMID- 7819081
TI  - Epstein-Barr virus in familial Hodgkin's disease.
AB  - Hodgkin's disease (HD) has been found to be linked to Epstein-Barr virus (EBV).
      Familial HD (FHD) may be related to a possible unknown agent. We have determined
      whether EBV small RNAs (EBERs) were found in Reed-Sternberg cells from FHD. Five
      families were studied for histological subtype and EBER presence. There was a
      striking similarity in FHD subtypes of each family and 3/11 (27%) of the cases
      were EBER positive. In conclusion, EBV EBERs are only infrequently found in FHD
      and other factors including viruses different from EBV should be further
      investigated in FHD.

PMID- 7819082
TI  - Kinetics of serum cytokines in adults undergoing peripheral blood progenitor cell
      transplantation.
AB  - We investigated the serum cytokine levels (G-CSF, GM-CSF, IL-1 beta, IL-3 and IL
      6) using an ELISA in 14 patients with haematological malignancies undergoing
      peripheral blood progenitor cell transplantation (PBPCT). Serum G-CSF levels in
      all patients rose immediately after PBPCT, then gradually decreased as the
      neutrophil counts began to rise. No detectable serum levels of GM-CSF or IL-1
      beta were observed, but serum levels of IL-3 rose transiently immediately
      following PBPCT. Serum levels of IL-6 rose transiently during a fever in four
      patients. These observations suggest that G-CSF and IL-3 may contribute to the
      early haemopoietic reconstitution in PBPCT.

PMID- 7819083
TI  - The role of CD45RO in antithymocyte globulin's stimulation of primitive
      haemopoietic cells.
AB  - We have found that antithymocyte globulin (ATG), an equine antibody with proven
      efficacy in aplastic anaemia (AA), has a direct stimulatory effect on primitive
      haemopoietic cells from normal donors. This growth stimulation may be mediated
      via anti-CD45RO activity present in the ATG preparation. Addition of unabsorbed
      ATG enhanced colony growth at 21 d in the blast colony forming cell (Bl-CFC)
      assay. Prior absorption of ATG by incubation with the CD45RO+ MOLT-4 cell line
      resulted in the loss of enhancement. Absorption by MOLT-4 cells preincubated with
      anti-CD45RO mAb, UCHL-1, restored ATG's stimulatory effect. The Bl-CFC could also
      be stimulated to grow by the addition of UCHL-1 directly. Incubation of the
      primitive haemopoietic cells for 4 h with ATG was associated with a decline in
      the antigenic density of CD45RO, a tyrosine phosphatase. This down-regulation may
      upset the balance between growth factor-induced tyrosine kinase activation and
      tyrosine phosphate dephosphorylation resulting in increased growth of primitive
      cells, a possible factor in the sustained recovery of haemopoiesis seen in AA
      patients after ATG treatment.

PMID- 7819084
TI  - Successful treatment of essential thrombocythaemia and recurrent abortion with
      alpha interferon.
AB  - A 27-year-old woman with essential thrombocythaemia (ET) had three miscarriages.
      She was treated with alpha interferon which was continued after she became
      pregnant again. The platelet count remained well controlled and at term she
      delivered a healthy baby with normal blood counts. The case demonstrates the
      effectiveness of IFN in preventing recurrent miscarriage associated with ET and
      the safety of IFN with respect to fertility and fetal development.

PMID- 7819085
TI  - Transfusion-associated graft-versus-host disease in fludarabine-treated B-chronic
      lymphocytic leukaemia.
AB  - Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare but serious
      complication of blood component therapy in patients with haematological
      malignancies. B-chronic lymphocytic leukaemia (B-CLL), however, has rarely been
      associated with TA-GVHD. We report three patients with advanced B-CLL who
      developed TA-GVHD. All these had been treated with fludarabine. Suppression of T
      cells by fludarabine may have contributed to an increased susceptibility to TA
      GVHD. The use of irradiated blood products to prevent this complication should be
      considered for patients with advanced B-CLL treated with fludarabine or other
      purine analogues.

PMID- 7819086
TI  - First report of fludarabine in gamma-heavy chain disease.
AB  - We describe a case of gamma-heavy chain disease presenting with lymphadenopathy,
      splenomegaly, lytic lesions and bone marrow infiltration. Chemotherapy with
      epirubicin, chlorambucil and prednisolone produced a partial remission which
      lasted 5 months. The patient was then treated with fludarabine. After six courses
      of fludarabine a good partial remission was achieved which converted to complete
      remission with disappearance of the monoclonal IgG3 in the ensuing 12 months
      without further therapy. This response has, so far, been sustained for 2 1/2
      years after stopping treatment.

PMID- 7819087
TI  - Haemophagocytic lymphohistiocytosis, interferon-gamma-naemia and Epstein-Barr
      virus involvement.
AB  - To clarify the correlation between Epstein-Barr virus (EBV) involvement and
      hypercytokinaemia in haemophagocytic lymphohistiocytosis (HLH), we analysed serum
      interferon-gamma levels and EBV-DNA in biological specimens obtained from 25 HLH
      cases (23 children and two adults). We found that HLH patients showed a wide
      range of serum IFN-gamma levels from 0.2 to 1300 U/ml, with a median 126 U/ml for
      EBV-DNA-positive (n = 9) and 4.5 U/ml for EBV-DNA-negative (n = 16) groups. The
      latter group could be classified further into a group with hyper-IFN-gamma-naemia
      (> 4.5 U/ml) (n = 8) and a group without hyper-IFN-gamma-naemia (n = 8). The
      survival of the hyper-IFN-gamma-naemic cases was significantly poorer than non
      hyper-IFN-gamma-naemic cases. We conclude that EBV is probably involved in one
      third of the HLH cases, all of whom show hyper-IFN-gamma-naemia, and in the half
      of the HLH cases with hyper-IFN-gamma-naemia who have a rapidly fatal outcome.

PMID- 7819088
TI  - Human platelet antigen-5 (Br) genotyping by ASPA: allele-specific primer
      amplification (PCR-SSP)
AB  - We have developed a PCR assay named ASPA (allele-specific primer amplification)
      to determine the HPA-5a and -5b genotypes. It consists of two PCR-reactions. One
      primer of each primer set has a 3'-end nucleotide which is specific for A or G at
      position 505 of the HPA-5b or -5a allele respectively. The HPA-5 genotypes
      determined in this way were strictly concordant with the genotypes established by
      the PCR-ASRA and with the phenotypes established using MAIPA. The ASPA is a rapid
      and reliable technique and can be used for the determination of alleles which
      code for platelet antigen allotypes.

PMID- 7819089
TI  - Erythropoietin treatment and platelet reconstitution in bone marrow
      transplantation.

PMID- 7819090
TI  - Respiratory burst activity in MDS and MPS patients.

PMID- 7819091
TI  - Primary cause of megaloblastic anaemia in Zimbabwe.

PMID- 7819092
TI  - Multiple myeloma: why does the disease escape from plateau phase?

PMID- 7819093
TI  - Evolving strategies for the treatment of myelomatosis.

PMID- 7819094
TI  - Dysplastic haemopoiesis following orthotopic liver transplantation: comparison
      with similar changes in HIV infection and primary myelodysplasia.
AB  - To validate scientifically our prior empiric observations that patients develop
      significant haemopoietic dysplasia following solid organ transplantation, we
      developed a quantitative lineage-specific scoring system to evaluate dysplastic
      features of bone marrow aspirates and core biopsies. We used this scoring system
      to compare retrospectively randomly selected bone marrow aspirates and core
      biopsies from 19 patients undergoing orthotopic liver transplantation (OLT), 21
      with a known history of human immunodeficiency virus (HIV) infection, and 18 with
      primary or chemotherapy-related myelodysplastic syndromes (MDS). Our results show
      that the OLT patient group developed significant but milder haemopoietic
      dysplastic changes than the HIV or MDS groups, and that the MDS group developed
      more severe dysplasia of the myeloid lineage than the other groups. The possible
      roles for drugs and infectious agents in the pathophysiology of dysplastic
      changes are discussed.

PMID- 7819095
TI  - Haemoglobin inhibits GTP-hydrolysis and GDP/GTP-exchange activities of a low M(r)
      GTP-binding protein, ras p21.
AB  - Haemoglobin was observed to inhibit the GDP/GTP-exchange activity of ras protein
      (ras p21) by measurement of [3H]GDP-dissociation activity in time- and dose
      dependent manners. Haemoglobin also inhibited the [32P]GTP-hydrolysis activity of
      ras p21 time- and dose-dependently. These inhibitory effects of haemoglobin were
      lost after incubation of haemoglobin at 80 degrees C for 3 min. Globin showed
      limited inhibition on the [32P]GTP-hydrolysis activity of ras p21, and haemin had
      no effect, indicating that the ternary tetrameric structure of haemoglobin is
      essential for the inhibitory effects on ras p21 activities. Methaemoglobin also
      inhibited both [3H]GDP-dissociation and [32P]GTP-hydrolysis activities of ras p21
      in a very similar manner to that by haemoglobin. The obtained results strongly
      suggest that haemoglobin suppresses the physiological function(s) of ras p21 in
      vivo inhibiting both [32P]GTP-hydrolysis and GDP/GTP-dissociation of ras p21 in
      erythrocytes.

PMID- 7819096
TI  - Human resident peritoneal macrophages: phenotype and biology.
AB  - Macrophages represent the primary line of host defences in the peritoneal cavity.
      In order to study the metabolic activity and maturation stage of human resident
      peritoneal macrophages (PM phi). peritoneal fluid (PF) was taken by Douglas
      puncture from healthy hyperstimulated infertile women undergoing oocyte retrieval
      for in vitro fertilization. Peritoneal fluid and macrophage culture fluids were
      studied for different inflammatory mediators such as interleukin-1 (IL-1), tumour
      necrosis factor (TNF) and interleukin-6 (IL-6). The level of macrophage colony
      stimulating factor (M-CSF), which represents a macrophage proliferation and
      differentiation factor, was determined in the PF and in the serum. Furthermore,
      the macrophage phenotypic profile was analysed, in particular the expression of
      sex steroid hormone receptors. IL-1. IL-6 and TNF were detectable in the PF and
      in the culture supernatants of PM phi whether stimulated or not by IFN-gamma and
      LPS. The mean level of M-CSF in the PF was 6.37 +/- 2.02 ng/ml as measured by
      RIA; this level did not correlate with the concentration of PM phi. The mean PF-M
      CSF level was 1.4-fold higher than in the sera as measured by a EIA. Oestrogen
      and progesterone receptors could not be demonstrated on the PM phi analysed, so
      that a direct relationship between the ovarian steroid concentration in these
      women and the function of PM phi was unlikely. As compared to peripheral blood
      monocytes (Mo). PM phi showed a phenotypic profile, with some more mature
      features, e.g. increased expression of CD14, CD68, FcRII, FcRIII, CR3, CR4 and
      MHC class II determinants. These results indicate that resident PM phi have
      acquired in vivo a certain differentiation and/or activation state under micro
      environmental factors where cytokines secreted by the M phi themselves or by
      other cells such as the mesothelium may play important roles.

PMID- 7819097
TI  - Haemophagocytic lymphohistiocytosis: experience at two U.K. centres.
AB  - Haemophagocytic lymphohistiocytosis (HLH) is a rare disorder of inappropriate
      macrophage activation. Both familial and sporadic forms, which may be infection
      associated, are recognized. Between 1985 and 1991 we treated 23 cases of HLH (12
      male, 11 female). There were eight familial cases, defined by a previously
      affected sibling and/or history of consanguinity, age 3 d to 15 months at
      presentation. The age of the remaining 15 cases varied from 1 month to 9.5 years.
      A potential viral trigger was identified in four cases (EBV, two; parvovirus B19,
      one; echovirus II, one) including one familial case. Six of eight (75%) patients
      who received supportive care alone, including all four familial cases, died
      within 6 months of presentation. Both long-term survivors in this group presented
      at an older age (7.5 and 8 years) and had proven or suspected virus-associated
      HLH. 15 patients were treated with etoposide (150-250 mg/m2 days 1-3 every 21 d)
      and methylprednisolone; 10 patients received intrathecal methotrexate in
      addition. In nine (60%) of these cases a complete (six) or partial (three)
      response was achieved, though one child suffered a fatal 'tumour lysis' syndrome.
      Overall mortality in the treated group was 66.6%, being highest (75%) in patients
      under 2 years at presentation compared to 33% in those over 2 years. Two of three
      familial and one of five sporadic cases relapsed and died 3 d to 20 months from
      diagnosis. Only one familial case survives at follow-up of 11 months. Of the five
      remaining survivors, two received allogeneic bone marrow transplantation (one
      matched related, one haploidentical) and are alive at 11 and 29 months. Three
      cases aged 2.5, 7.5 and 9.5 years remain in remission at 11, 20 and 25 months
      respectively. The high mortality of HLH supports a role for allogeneic BMT in
      selected cases, particularly those with a familial basis or under 2 years at
      presentation.

PMID- 7819098
TI  - A luminescence method for the quantitative determination of phagocytosis of
      erythrocytes, of malaria-parasitized erythrocytes and of malarial pigment.
AB  - A method is described for the quantitative measurement of phagocytosis of human
      erythrocytes, malaria-parasitized erythrocytes and isolated malarial pigment by
      adherent human monocytes. The method utilizes measurement of haem-elicited
      luminescence both for the assay of ingested haemoglobin or malarial pigment haem
      and for the quantification of adherent monocytes. The latter is based on assay of
      luminescence elicited by cytochrome haem. The method utilizes the same low-cost
      reagents and equipment for assay of ingested haem and for quantification of
      adherent monocytes. The method is fast and extremely sensitive. The lower
      sensitivity limit is 500 monocytes and 10 RBC, or RBC equivalents in the case of
      malarial pigment, per assay. A detailed protocol with full calculations of a
      typical phagocytosis experiment of oxidatively damaged RBC, malarial pigment and
      control RBS is presented.

PMID- 7819099
TI  - The endocytic pathway for H-ferritin established in live MOLT-4 cells by laser
      scanning confocal microscopy.
AB  - We have established the intracellular destination of the putative
      immunoregulatory protein, human recombinant H (heavy)-ferritin, in the
      transformed T-cell line MOLT-4, by laser scanning confocal microscopy of live
      cells. A series of confocal images was collected over a 60 min time course using
      indirect immunofluorescence of H-ferritin and transferrin, their respective
      monoclonal antibodies, and fluorescein isothiocyanate (FITC)-labelled IgG. A
      marked drop in FITC fluorescence after 40 min of H-ferritin internalization,
      indicative of an acidic environment, and co-localization with
      tetramethylrhodamine isothiocyanate-labelled-dextran strongly suggests that H
      ferritin is transferred to the lysosome. In contrast, transferrin was observed to
      return to the cell surface. Electron microscopy confirmed that H-ferritin was
      transferred to the lysosome. The receptor-mediated endocytosis and lysosomal
      delivery of H-ferritin may thus potentiate its putative immunoregulatory
      activity.

PMID- 7819100
TI  - Primary plasma cell leukaemia.
AB  - Among 750 previously untreated patients with multiple myeloma, 27 (4%) presented
      with plasma cell leukaemia. All but one patient had high tumour mass and, when
      compared with comparable patients without leukaemia, more frequent extraosseous
      involvement, thrombocytopenia, high serum lactate dehydrogenase and hypodiploid
      plasma cells. Most patients also had complex cytogenetic abnormalities. Treatment
      with standard melphalan-prednisone was ineffective, with a median survival of 2
      months, but more intensive chemotherapy induced responses in approximately one
      half of the patients, with a median survival of 20 months. Primary plasma cell
      leukaemia usually results from the proliferation and extramedullary expansion of
      immature plasma cells and requires prompt and intensive chemotherapy.

PMID- 7819101
TI  - Prognostic value of serum IL-10 and soluble IL-2 receptor levels in aggressive
      non-Hodgkin's lymphoma.
AB  - We investigated the prognostic significance of interleukin-10 (IL-10) and soluble
      interleukin-2 receptor (sIL-2r) levels in the pretreatment serum of 105
      individuals with newly-diagnosed aggressive non-Hodgkin's lymphoma (NHL).
      Commercially available enzyme-linked immunoassay kits were used for cytokine and
      receptor measurements. Detectable levels of IL-10 were found in 42 (40%) patients
      at diagnosis, with no correlation with clinico-haematological parameters, but in
      no control samples (P < 0.001). Pretreatment concentrations of sIL-2r were
      markedly increased in individuals with NHL when compared to controls (2614 +/-
      893 U/ml v 219 +/- 65 U/ml, P < 0.001), patients with stage III/IV presenting
      higher values than those with stage II disease (3885 +/- 1196 U/ml v 1732 +/- 646
      U/ml, P < 0.001). No single parameter was associated with the achievement of
      complete remission, but the combination of elevated IL-10 and of sIL-2r greater
      than 3000 U/ml selected a subset of patients with a high probability of failing
      induction therapy (P < 0.001). Life-table analysis also indicated that patients
      with these characteristics have a significantly shorter event-free survival. In a
      multivariate analysis the combination of IL-10 with sIL-2r was found to have
      greater predictive strength than the combination of IL-10 with beta 2
      microglobulin. We conclude that IL-10 and sIL-2r measurements can be expected to
      improve existing methods of risk assignment in aggressive NHL.

PMID- 7819102
TI  - Metaphase fluorescence in situ hybridization (FISH) in the follow-up of 60
      patients with haemopoietic malignancies.
AB  - Metaphase DNA fluorescence in situ hybridization (metaphase-FISH) was performed
      on follow-up samples from 60 patients suffering from haemopoietic malignancies
      (acute and chronic myeloid leukaemia, acute lymphoblastic leukaemia, non
      Hodgkin's lymphoma and myelodysplastic syndrome). All patients had clonal
      chromosomal trisomies or translocations at diagnosis, and were treated by bone
      marrow transplantation (BMT), chemotherapy (CT) or interferon-alpha therapy.
      Metaphase-FISH was performed during therapy-induced complete haematological
      remission (CR) (BMT and CT patients) using biotin-labelled whole chromosome paint
      probes. 28% of all patients in CR were shown by FISH to have abnormal metaphase
      cells, and 62% of this group suffered a clinical relapse. Of those with negative
      FISH results (72%), 12% relapsed. In three CML patients treated with BMT a small
      population of t(9;22)-positive cells was demonstrated. These cells disappeared
      during follow-up without causing a relapse. One ALL patient had abnormal cells a
      short time after start of therapy but was also later found FISH-negative.
      Furthermore, we demonstrated that metaphase-FISH is a suitable method for
      quantifying the proportion of abnormal cells in CML patients during interferon
      alpha therapy. Metaphase-FISH was also employed to detect a local relapse in an
      ALL patient. Thus, metaphase-FISH was found reliable and sensitive for detection
      of minimal residual disease in patients with haemopoietic malignancies.

PMID- 7819103
TI  - Minimally differentiated acute myeloid leukaemia (AML-M0): cytochemical,
      immunophenotypic and cytogenetic analysis of 19 cases.
AB  - We describe our experience in the identification of 19 cases of AML-M0
      categorized among 200 consecutive AML cases. Leukaemic cells from our cases were
      morphologically marked by agranular basophilic cytoplasm, finely dispersed
      chromatin and prominent nucleoli. In two cases heavily vacuolated and monocytoid
      shaped blasts were also observed. Cytochemistry (MPO, SBB, alpha ANAE, alpha NBE,
      NASDCAE, AP, PAS) was negative in 14 cases, five cases expressing a very faint
      cytoplasmic positivity for alpha NBE (not exceeding 30% of the blasts) and alpha
      ANAE (not exceeding 41%) which was sodium fluoride resistant. In these five cases
      other monocytic markers (e.g. CD14) were not in favour of myelomonocytic
      differentiation. All the cases were anti-MPO positive at frequency > 10%.
      Phenotypic analysis also revealed myeloid features with all the patients having
      at least one myeloid antigen (CD13, CD33, CD15), Tdt was expressed in nine cases
      and CD7 in six cases. All cases but one were positive for CD34. Cytogenetic
      analysis, performed in 16 cases, showed no adequate growth in two cases and no
      consistent abnormality in four; among the remaining 10 cases no consistent
      abnormality was observed, the most common finding was trisomy 8 (two cases) and 4
      (two cases) and aberrations of chromosomes 2, 3, 5, 7, 9, 12 and 21. No cases of
      (t9;22), Ph chromosome were observed. Interestingly three out of five patients
      with faint alpha NBE/alpha ANAE positivity relapsed as typical M4 (one case) or
      M5a (two cases).

PMID- 7819104
TI  - Molecular analysis of the erythropoietin receptor system in patients with
      polycythaemia vera.
AB  - Erythropoietin (EPO) is a potent regulator of the viability, proliferation and
      differentiation of erythroid progenitor cells. Its effect is mediated by binding
      to the erythropoietin receptor (EPO-R), a member of a new cytokine receptor
      family. Alterations of the EPO/EPO-R system have recently been shown to be
      involved in the pathogenesis of familial erythrocytosis and polycythaemia vera
      (PV). In order to define whether genetic changes in the EPO-R gene and its ligand
      play a role in the development of PV, the structure and expression levels of the
      EPO-R and EPO genes were examined in samples from bone marrow and/or peripheral
      blood mononuclear cells of 24 patients with PV. As expected, EPO serum levels
      were low and no detectable level of EPO mRNA was found by reverse polymerase
      chain reaction (RT-PCR) in the peripheral blood mononuclear cells of our PV
      patients. To search for structural alterations of the EPO-R, cDNA samples were
      subjected to PCR and SSCP analysis as well as sequencing. Heterogenous expression
      of EPO-R mRNA was observed without any structural changes, as revealed by RT-SSCP
      analysis using overlapping primers spanning the whole coding region of the EPO-R
      gene. Structural integrity of the EPO-R was further confirmed by sequencing of
      cloned PCR products. These data suggest that the mechanisms for the development
      of PV do not involve structural changes of the EPO-R gene.

PMID- 7819105
TI  - Role of ADP in platelet aggregation at high shear: studies in a patient with
      congenital defect of platelet responses to ADP.
AB  - The in vitro measurement of platelet aggregation (PA) at the high shear levels
      that can be found in the microcirculation may provide useful informations on
      primary haemostasis, which is usually explored in vivo with the skin bleeding
      time (BT). PA at high shear requires von Willebrand factor (vWf) and the platelet
      glycoprotein (GP) complexes Ib/IX/V and IIb/IIIa; controversial results have been
      reported on its requirement of released adenosine diphosphate (ADP). Due to its
      dependence on vWf, PA at high shear may be affected by the vasopressin analogue
      DDAVP, which increases the plasma vWf levels and shortens the prolonged BT of
      patients with congenital or acquired defects of platelet function. We studied PA
      at high shear, BT and plasma vWf levels in a patient with congenital impairment
      of platelet responses to ADP before and after the i.v. infusion of 0.3
      micrograms/kg DDAVP. Two methods to study PA at high shear were used: shear
      induced PA (SIPA) and the filter aggregation test. With both methods, PA at high
      shear of the patient was impaired. The infusion of DDAVP increased plasma vWf
      levels, shortened the prolonged BT and potentiated PA at high shear of the
      patient. In conclusion, PA at high shear is impaired in a patient with congenital
      defect of platelet responses to ADP and prolonged BT and is potentiated by DDAVP.
      Our results suggest that released ADP plays an important role in PA at high shear
      and that potentiation of PA at high shear by DDAVP may be one mechanism by which
      the drug shortens the prolonged BT of patients with congenital or acquired
      defects of platelet function.

PMID- 7819107
TI  - Cys209 Ser mutation in the platelet membrane glycoprotein Ib alpha gene is
      associated with Bernard-Soulier syndrome.
AB  - Molecular genetic analysis has been performed on a patient with Bernard-Soulier
      syndrome (BSS). The patient had characteristically giant platelets and was
      deficient in the glycoprotein (GP) Ib/IX/V complex, the von Willebrand factor
      (vWf) receptor on platelets. Previous studies with monoclonal antibodies directed
      against GP Ib alpha (CD 42b) and GP IX (CD 42a) demonstrated the absence of GP Ib
      alpha and presence of small amounts of GP IX on the surface of the patient's
      platelets. In this study the presence of GP V (CD 42d) is also demonstrated. This
      indicates a defect in the alpha-subunit of glycoprotein Ib. Therefore polymerase
      chain reaction (PCR)-amplification of the genomic DNA coding for GP Ib alpha was
      performed. Nucleotide sequence analysis of the entire coding region of GP Ib
      alpha revealed a homozygous single base pair mutation T-->A, leading to a single
      amino acid substitution cysteine-->serine at position 209 of the mature protein.
      We took advantage of the Mse I target site in the mutant allele, created by the T
      ->A mutation, to analyse all available family members. PCR-ASRA (allele-specific
      restriction enzyme analysis) using the restriction enzyme Mse I, revealed the
      heterozygosity of the mother and the two children of the patient, whereas
      homozygosity of the patient for the Cys209Ser mutation was confirmed. The sister
      of the patient was not found to be a carrier of the mutant allele. The mutation
      identified in the family studied, responsible for the deficiency of the GP
      Ib/IX/V complex, suggests that the cysteine at amino acid position 209 may be
      involved in disulphide bonding.

PMID- 7819106
TI  - Platelet shape change and Ca2+ mobilization induced by collagen, but not thrombin
      or ADP, are inhibited by phenylarsine oxide.
AB  - In this report we have examined the effects of the protein tyrosine phosphatase
      inhibitor phenylarsine oxide (PAO) on receptor-mediated platelet shape change,
      secretion and aggregation. PAO was found to inhibit platelet aggregation induced
      by collagen, thrombin, ADP and epinephrine at IC50 values of 0.35 mumol/l, 2.5
      mumol/l, 0.2 mumol/l and 0.3 mumol/l, respectively. Agonist-induced secretion of
      ATP was inhibited at similar or lower concentrations of PAO. The specificity of
      the interaction of PAO with platelet proteins was demonstrated by the ability of
      the disulfhydryl compound 2,3-dimercaptopropanol, which abstracts PAO from
      proteins to form a stable cyclic adduct, to reverse PAO inhibition of both
      agonist-induced platelet secretion and aggregation. Dimercaptopropanesulphonic
      acid, a membrane-impermeable analogue of dimercaptopropanol, did not reverse
      inhibition of collagen-induced shape change or aggregation by PAO, thereby
      demonstrating that PAO acted intracellularly. PAO inhibited collagen-induced
      shape change and internal Ca2+ mobilization but had no effect on these two
      phenomena when induced by thrombin or ADP. PAO was also unable to prevent
      arachidonic acid-induced shape change, indicating that PAO acts at a site prior
      to the phospholipase A2-mediated release of arachidonic acid to inhibit collagen
      induced shape change. PAO induced the accumulation of a number of phosphotyrosine
      containing proteins and inhibited the collagen-induced phosphorylation of a 40 kD
      protein. The potency and agonist-specific effects of PAO on platelet activation
      suggest that this inhibitor will be of value in elucidation of signal
      transduction pathways involved in receptor-mediated platelet function.

PMID- 7819108
TI  - The development of antiphospholipid antibodies in haemophilia is linked to
      infection with hepatitis C.
AB  - In haemophilia the presence of antibodies to antiphospholipid has been linked
      with HIV infection, but other possibilities have not been fully explored and the
      specificity for various phospholipids not established. In order to investigate
      further the pathogenesis and clinical significance of these antibodies, we have
      determined IgG and IgM antibodies to a variety of phospholipids, including
      cardiolipin, in the serum of 52 haemophiliacs, and related our findings to the
      presence of antibodies to HIV and hepatitis C virus (HCV), as well as to clotting
      factor concentrate usage and blood markers of liver biochemistry. Our results
      demonstrate that the presence of infection with hepatitis C virus is strongly
      associated with raised serum levels of antiphospholipid antibody even in the
      absence of HIV infection. They suggest that earlier conclusions on the
      relationships of antiphospholipid to HIV infection in haemophilia should be
      revised and that chronic infection with the hepatitis C virus should be added to
      the list of infective causes for the development of antiphospholipid antibody.

PMID- 7819109
TI  - Biological effect of desmopressin in eight patients with type 2N ('Normandy') von
      Willebrand disease. Collaborative Group.
AB  - It is generally thought that the plasma increase in factor VIII (FVIII) after
      desmopressin (dDAVP) infusion is related to the plasma increase in von Willebrand
      factor (vWF), which is the plasma carrier for FVIII. The aim of this study was to
      evaluate the FVIII and vWF responses in patients with type 2N vWD, characterized
      by the mild FVIII deficiency related to markedly decreased affinity of vWF for
      FVIII. At different times after one intravenous dose of dDAVP (0.3 or 0.4
      microgram/kg) we measured the FVIII coagulant activity, FVIII antigen, vWF
      antigen and ristocetin cofactor activity, in eight patients with either Arg91Gln
      or Arg53Trp amino acid substitution in mature vWF. In all the patients, whatever
      their mutation, the dDAVP infusion resulted in a 2.3 +/- 0.7-fold increase of vWF
      and a variable rise (9.5 +/- 7.7 times) of FVIII, whereas the vWF capacity to
      bind FVIII was not improved. The FVIII response was more transient than vWF
      response, and FVIII half disappearance time was evaluated to be approximately 3
      h. The data indicate that the stabilizing effect of vWF on FVIII is not
      responsible for the FVIII increase induced by dDAVP. The clinical implication of
      this study is that, in the 2N vWD patients, dDAVP may be a useful prophylactic or
      curative treatment when the test dose has been shown to be effective to reach a
      haemostatic FVIII level.

PMID- 7819110
TI  - Isolation and culture of endothelial cells from human bone marrow.
AB  - Adhesive interactions between haemopoietic progenitor cells and bone marrow
      sinusoidal endothelium are potentially important in the homing of these cells
      back to the extravascular compartment of the marrow to re-establish haemopoiesis
      following stem cell transplantation. A simple method for the isolation and
      culture of human bone marrow endothelial cells is described using bone marrow
      aspirates obtained from patients undergoing bone marrow harvests for autologous
      or syngeneic bone marrow transplantation. The method is based on the selective
      binding of the lectin Ulex europaeus agglutinin-1 (UEA-1) to endothelial cells.
      Magnetic Dynabeads coupled with UEA-1 were incubated with single cell suspensions
      of bone marrow following red cell lysis, and bound cells were isolated with a
      magnet. The isolated cells demonstrated positive immunofluorescence staining for
      von Willebrand factor. Cells were plated onto tissue culture flasks coated with
      extracellular matrix derived from human umbilical vein endothelial cells in an
      endothelial serum-free medium together with 5% fetal calf serum for 24 h. Cells
      were then cultured in endothelial serum-free growth medium supplemented with 5%
      fetal calf serum, endothelial cell growth supplement and heparin. After 2-4 weeks
      in culture, two morphologically different cell populations can be identified. One
      has a polygonal spindle-shaped morphology with a rapid growth rate, the other a
      rounded morphology and a slow growth rate. Both populations have a vesiculated
      cytoplasm. Positive immunostaining of the cells was demonstrated with a number of
      endothelial cell markers including von Willebrand factor, and antibodies to ICAM
      1, VCAM-1, E-selectin, CD31 and BMA120. Weibel-Palade bodies were observed by
      electron microscopy. Culture of these cells will allow detailed in vitro studies
      of adhesion mechanisms in the homing of haemopoietic progenitor cells.

PMID- 7819111
TI  - The reliability of the mean normal prothrombin time of fresh plasmas and of the
      normal value from a lyophilized 'normal' plasma in prothrombin ratio
      determination.
AB  - The mean normal prothrombin time (MNPT) based on the fresh plasma of 20 healthy
      individuals is the recommended way to derive a normal value for the prothrombin
      ratio. This is generally believed to give a reasonable representation of the
      normal in the local population, but there may be difficulty in obtaining a good
      representative sample in some centres. The alternative of a uniform lyophilized
      'normal' plasma has been suggested. The comparative value of a widely used
      commercial 'normal' plasma and the MNPT has been assessed in an international
      study at 37 centres. Two common thromboplastins were tested using the local
      coagulometer methods. The variability of the results and their relative
      performance in local thromboplastin calibration to derive the International
      Sensitivity Index (ISI) were assessed. The reliability of the two types of normal
      in local system ISI calibration with different lyophilized plasma calibrants has
      also been tested. When the lyophilized 'normal' was substituted for the MNPT in
      ISI determination no appreciable difference in the degree of correction for
      coagulometers effects on International Normalized Ratios was found.

PMID- 7819112
TI  - In vitro culture of colony forming unit-megakaryocyte (CFU-MK) in fetal
      alloimmune thrombocytopenia.
AB  - Perinatal alloimmune thrombocytopenia (PAITP) causes intracranial haemorrhage in
      the fetus and neonate. However, the severity of the thrombocytopenia correlates
      poorly with maternal anti-platelet antibody titres. To test the hypothesis that
      reduced platelet production contributes to fetal thrombocytopenia in PAITP,
      maternal sera from three HPA-1a-negative mothers whose pregnancies were
      complicated by anti-HPA-1a (two severe cases, one mild case) were added to colony
      forming unit-megakaryocyte (CFU-MK) cultures from HPA-1a positive and negative
      individuals. Sera from the two severely affected pregnancies containing anti-HPA
      1a caused 66-100% inhibition of HPA-1a-positive fetal and neonatal CFU-MK,
      whereas CFU-MK from two HPA-1a-negative mothers were not inhibited by the anti
      HPA-1a-containing sera. Maternal serum from the case of mild PAITP caused only
      mild inhibition of HPA-1a-positive cord and adult CFU-MK and did not inhibit HPA
      1a-positive fetal CFU-MK. Taken together, these findings suggest that reduced
      megakaryocyte production contributes to fetal thrombocytopenia due to maternal
      anti-HPA-1a antibodies and also that the degree of CFU-MK inhibition correlates
      with severity of fetal thrombocytopenia.

PMID- 7819113
TI  - Novel small deletions of the p53 gene in late-stage B-cell chronic lymphocytic
      leukaemia.
AB  - A group of 20 CLL patients selected for advanced clinical stage p53 mutations
      were analysed by single-strand conformational polymorphism (SSCP) following PCR
      amplification of exons 5-9. In two patients abnormal SSCP of either exon 5 or
      exon 8 was found and PCR products were analysed by direct sequencing. A
      hemizygous or homozygous 12bp deletion at codon 135 and 3bp heterozygous deletion
      at codon 264 were detected; also, in the latter sample a heterozygous mutation at
      codon 282 (Arg to Gln) was found. To our knowledge, this is the first report of
      p53 deletions in B-CLL. The two patients were elderly, and both had a rapidly
      progressive disease in the absence of unfavourable cytogenic abnormalities. These
      findings support a role for p53 alterations in the clinical course of some B-CLL
      patients.

PMID- 7819114
TI  - Correlation between disease activity and T-cell CD3 zeta chain expression in a B
      cell lymphoma.
AB  - The T-cell receptor (TCR)/CD3 complex is the surface molecule responsible for the
      highly specific response to foreign antigens, including tumour-associated
      antigens. and correlations have been observed with disease status. Recently, low
      amounts of CD3 gamma and CD3 zeta chains in the CD3/TCR complex have been
      reported in long-term tumour-bearing mice as a possible mechanism for the
      impaired T-cell responses. In this study we report a B-cell lymphoma in which T
      cell CD3 zeta expression correlated with disease activity.

PMID- 7819115
TI  - Intragenic dinucleotide repeats in factor VIII gene for the diagnosis of
      haemophilia A.
AB  - Two multi-allelic microsatellite polymorphisms within the factor VIII gene were
      studied in 138 Chinese subjects. The allele sizes detected were higher than those
      found in Caucasian populations, whereas the heterozygosity rates were lower,
      being 0.5370 for intron 13 and 0.4444 for intron 22 repeats respectively. Their
      usefulness in diagnosis was compared to other intragenic and extragenic RFLPs,
      using previous data on the same 31 unrelated haemophilia A families. These
      intragenic microsatellite repeat polymorphisms were only informative for 18/31
      families (58%); however, with the combined use of all existing RFLPs, the
      cumulative informativeness would be 100%.

PMID- 7819116
TI  - A distinct coagulopathy associated with interleukin-2 therapy.
AB  - We studied the coagulation profiles of 14 patients with advanced malignancies
      treated with Interleukin-2 (IL-2). A 43% prolongation of the PTT (P < 0.001) and
      a significant decrease in functional levels of factors II, IX, X, XI, and XII
      were observed 6 h post IL-2 treatment in comparison to pretreatment values. These
      parameters normalized within 2-3 d following IL-2 administration. The PT, factors
      V, VII, VIII, fibrinogen and D-dimer levels were unchanged with IL-2 treatment.
      This pattern of coagulopathy has not previously been reported.

PMID- 7819117
TI  - Lack of evidence for parvovirus B19 viraemia in children with chronic
      neutropenia.

PMID- 7819118
TI  - Establishing the incidence of myelodysplasia syndrome.

PMID- 7819119
TI  - Expression of myeloid antigens in acute lymphoblastic leukaemia.

PMID- 7819120
TI  - Morphological detection of X- and Y-chromosomes in smears and paraffin-embedded
      tissues using a non-isotopic in situ hybridization technique (NISH).
AB  - Pharyngeal smears and paraffin-embedded tissue specimens (skeletal muscle,
      kidney) obtained from 10 male and 10 female individuals were evaluated using non
      isotopic in situ hybridization (NISH) with commercial X- and Y-specific
      biotinylated probes which recognize the pericentromeric regions DXZ1 and
      DYZ1/DYZ3 of the X- and Y-chromosome, respectively. The results provide evidence
      that the morphological sex determination of a single cell can be performed by
      critical application of this staining method leading to one nuclear signal in
      "male" cells using the Y-specific probe whereas "female" cells are negative. In
      situ hybridization of "female" tissues with an X-specific probe results regularly
      in 2 signals whereas "male" cells show only one spot in the nucleus.

PMID- 7819121
TI  - Legal medicine in Europe--Quo vadis?

PMID- 7819122
TI  - Immunohistochemical investigation of hypoxic/ischemic brain damage in forensic
      autopsy cases.
AB  - A neuropathological study of 41 forensic autopsy cases of hypoxic/ischemic brain
      damage has been undertaken, using immunohistochemical staining to detect the 70
      kDa heat shock protein (hsp70) and the status of the glial cells. In cases
      surviving 2-5 h after hypoxic/ischemic injury, ischemic cell changes were seen
      whereas glial reactions were not apparent. In cases of longer survival, neuronal
      necrosis and a loss of neurons were seen, and these changes were accompanied by
      proliferation of glial fibrillary acidic protein (GFAP), vimentin-positive
      astrocytes and microglia which transformed into rod cells or lipid-laden
      macrophages. In cases with a history of hypoxic attacks, GFAP-positive and
      vimentin-negative astrocytes had proliferated in the CA3 and CA4 regions of
      hippocampus. The cases of severe hypoxic injury, such as an asthmatic attack and
      choking, showed no ischemic changes in the hippocampal neurons. On the other
      hand, the CA1 pyramidal cells showed neuronal necrosis in a patient suffering
      from tetralogy of Fallot (TOF), who survived for 2 h after a traffic accident.
      Therefore, it is suggested that even moderate hypoxic injury induces astrocytosis
      in the CA3 and CA4 regions and may affect the neuronal proteins and the
      metabolism, and that in cases with a history of hypoxic attacks neuronal damage
      may be severe even several hours after ischemic injury. The protein hsp70
      expression was found in the CA2, CA3 and CA4 regions in cases of long-term
      survival after severe hypoxic/ischemic injury and in cases of alcoholic intake or
      toluene abuse just before acute death.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7819123
TI  - The validation of short tandem repeat (STR) loci for use in forensic casework.
AB  - A quadruplex reaction has been developed which amplifies the short tandem repeat
      (STR) loci HUM-VWA31/A, HUMTHO1, HUMF13A1 and HUMFES/FPS. Detection of the PCR
      products employs denaturing polyacrylamide gels coupled with fluorescent-based
      technology. This system has been evaluated for use in routine forensic casework
      and has been shown to be both robust and reproducible. The quadruplex reaction is
      as sensitive as the commercially available HLA DQ alpha Amplitype typing system
      and can be used on both degraded and aged material. The problems of environmental
      contamination have been shown to be limited provided strict procedural practices
      are followed-i.e. physical separation of sample extraction and amplified
      products; the use of dedicated equipment such as pipettes; the separation of
      amplification preparation area. The ability of the system to detect mixtures and
      the successful analysis of case stains has shown that this system is well suited
      as a tool for forensic investigation.

PMID- 7819124
TI  - Iatrogenic fatal outcome of traumatic axillary aneurysm.
AB  - Five months after dislocation of the left shoulder a 66-year-old patient noted a
      swelling in the left axilla. After CT-scan a malignant tumour was suspected and
      an incisional biopsy was performed. A week later the patient died due to
      hemorrhaging from the biopsy wound. The autopsy revealed a false aneurysm of the
      axillary artery. The incision had damaged the external wall of the aneurysm
      leading to consecutive rupture. Post-mortem findings are presented.

PMID- 7819126
TI  - Expression of mitochondrial benzodiazepine receptor and its putative endogenous
      ligand diazepam binding inhibitor in cultured primary astrocytes and C-6 cells:
      relation to cell growth.
AB  - A recognition site for benzodiazepines structurally different from that linked to
      the gamma-aminobutyric acid receptor subtype A or the "central type"
      benzodiazepine receptor has been located mainly in the outer membranes of
      mitochondria and designated mitochondrial benzodiazepine receptor (MBR). A
      putative endogenous ligand for MBR is the peptide, diazepam binding inhibitor
      (DBI), which inhibits benzodiazepine ligand binding in mitochondrial membranes.
      In this study, DBI- and MBR-like immunoreactivities (LI) were examined at the
      cellular and ultrastructural levels, and their changes during cell growth were
      followed in rat primary cerebellar astroglial and C-6 cell cultures. During the
      early stages of the cultures (7-14 days in vitro), MBR and DBI were expressed
      virtually in all astrocytes and C-6 cells of the cultures. The highest MBR/DBI
      immunoreactivity was observed in dividing cells. When the astrocytes had formed a
      confluent layer (21 days in vitro), MBR staining intensity was significantly
      decreased. Electron microscopic analysis demonstrated an even distribution of DBI
      LI throughout the cytoplasm, while MBR-LI was mainly observed in a close
      association with the outer mitochondrial membranes. However, dividing cells also
      displayed strong MBR immunoreactivity in endoplasmic reticulum, nuclear
      membranes, and centrioles. Treatment of the confluent cultures with MBR ligands
      PK 11195 and Ro 5-4864 at nanomolar concentrations increased the density of MBR
      LI and the progesterone content in the medium 2-3-fold over the basal levels.
      These results demonstrate a close association between DBI and mitochondrial
      benzodiazepine receptors and lend support to the theory that they have a possible
      role in the regulation of steroid production. The relation of MBR and DBI
      expression to cell growth and division suggests a novel role for these elements
      in the regulation of important intracellular events.

PMID- 7819127
TI  - Alternative messenger RNA forms and open reading frames within an additional
      conserved region of the human PAX-2 gene.
AB  - PAX-2 is a member of a family of genes containing a highly conserved paired box
      domain. The paired box domain encodes a DNA binding motif, indicating that PAX
      proteins may function as transcriptional regulators, participating in a
      hierarchical network of gene regulation during embryogenesis. In this report, we
      provide evidence that there is an additional conserved region near the predicted
      COOH-terminus of PAX-2, PAX-5, and PAX-8. We also describe alternative splicing
      of a conserved 83-nucleotide segment in the 3' coding sequence of the PAX-2 gene.
      PAX-2 transcripts that contain the 83-nucleotide insertion encode a putative
      protein with an alternative COOH-terminus. The presence of an additional
      conserved region and alternative splicing within the predicted COOH-terminal
      region of several PAX genes has implications for the evolutionary origins and for
      the DNA binding site specificity of PAX-2, PAX-5, and PAX-8.

PMID- 7819125
TI  - Traumatic lesion of the extracranial vertebral artery--a note-worthy potentially
      lethal injury.
AB  - The autopsy findings from routine neuropathological investigations of the
      cervical spine after any history of trauma emphasized the vulnerability of the
      extracranial vertebral arteries. In 21 cases with trauma to the head and neck,
      normal autopsy procedures did not succeed in revealing an obvious cause of death.
      Traumatic lesions of the spinal cord such as contusion or neurorrhexis were seen
      in 10 cases. In 15 cases we observed different degrees and stages of traumatic
      lesions of the extracranial vertebral arteries. Sudden death due to acute brain
      stem ischemia might be considered as an explanation in some of these cases. Six
      case reports with traumatic vertebral artery (VA) lesions after severe or minor
      extracranial trauma are presented. A review of the literature revealed that this
      vascular injury has only rarely been directly established by gross pathological
      examination. Possible consequences of blunt trauma to the head and neck include
      angiorrhexis, subintimal, intramural and perivascular hemorrhage leading to a
      partial narrowing of the injured vessel. These processes can be complicated by
      thrombosis. Unilateral VA obliteration may be an occult risk of acute brain stem
      ischemia when associated with contralateral reduction of the posterior
      circulation.

PMID- 7819128
TI  - The role of nm23 in transforming growth factor beta 1-mediated adherence and
      growth arrest.
AB  - nm23 has properties of a metastasis suppressor gene and also has been implicated
      in the control of response to transforming growth factor beta 1 (TGF beta 1) by
      studies in melanoma cells. In this report, we have examined the role of nm23 in
      two HT29 colon carcinoma sublines at different stages in tumor progression with
      different responses to TGF beta 1: the HD3 subline, which shows TGF beta 1
      induced growth arrest and differentiation; and the more invasive and tumorigenic
      U9 subline, which induces tumors 7-fold as large as those induced by HD3 cells
      with one-half the latency. Analysis by semiquantitative reverse transcription
      polymerase chain reaction showed that antisense phosphorothiolated
      oligonucleotides to the nm23 initiation site (nm23 AS oligos) decreased nm23 mRNA
      levels 2-8-fold in HD3 and U9 cells when normalized to beta-actin mRNA levels.
      However, a role for nm23 in TGF beta 1-mediated responses could only be found in
      HD3 cells. nm23 AS oligos inhibited the differentiation property of cell
      adherence over 90% in HD3 cells, and this loss of adherence could be partially
      blocked by concurrent treatment with TGF beta 1. In contrast, U9 cell adherence
      was not detectably altered by nm23 AS oligos, whether added in the presence or
      absence of TGF beta 1. The TGF beta 1-induced inhibition of HD3 cell
      proliferation was blocked by nm23 AS oligos, whereas the TGF beta 1-induced
      proliferation of U9 cells was unaffected by nm23 AS oligos.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7819129
TI  - Transforming growth factors beta 1, beta 2, and beta 3 messenger RNA and protein
      expression in mouse uterus and vagina during estrogen-induced growth: a
      comparison to other estrogen-regulated genes.
AB  - Increasing evidence suggests that the differential regulation of multiple peptide
      growth factors by steroid hormones contributes significantly to the pleiotropic
      effects elicited in target tissues. We report here an evaluation of the effects
      of the potent estrogen, diethylstilbestrol, on the expression of the three
      mammalian transforming growth factor beta (TGF beta) isoforms, TGF beta 1, TGF
      beta 2, and TGF beta 3, in both the uterus and the vagina of the prepubescent
      mouse. Immunohistochemical protein detection, in situ hybridization, and Northern
      RNA analyses demonstrate overlapping but distinct time-dependent and site
      specific induction of all three TGF beta genes in the reproductive tract in
      response to estrogen. Temporal analysis of steady-state levels of the TGF beta
      mRNAs in the uterus by Northern blotting clearly demonstrates that
      diethylstilbestrol significantly but transiently up-regulates TGF beta 3 mRNA
      within 30 min and TGF beta 1 and TGF beta 2 mRNAs by 3 h with decreases to/or
      below control levels by 6 h. The vagina also responds to diethylstilbestrol with
      similar kinetics of induction for TGF beta 2 and TGF beta 3 mRNAs as that
      observed in the uterus; however, TGF beta 1 mRNA levels increase gradually and
      peak around 16 h after treatment. Investigation of the steroid specificity
      demonstrates predominant estrogen specificity in the control of TGF beta
      expression in the immature mouse reproductive tract. In situ hybridization
      localizes the mRNAs for all three TGF beta isoforms, primarily to the uterine and
      vaginal epithelium. Unlike the transient nature of TGF beta mRNA induction
      elicited by estrogen, immunohistochemistry demonstrates that estrogen treatment
      results in a more prolonged elevation of the proteins for TGF beta 1, TGF beta 2,
      and TGF beta 3 in the epithelium of both tissues. Investigation of specific
      binding of 125I-TGF beta 1 by affinity labeling reveals the existence of the
      receptor/binding proteins (types I, II, and III) in the uterus. Estrogen
      treatment significantly reduces binding to each of these components in the
      uterus, which suggests that estrogen may modulate TGF beta responsiveness at the
      receptor level. A comparison of TGF beta mRNA expression to the induction of
      other estrogen-regulated genes, TGF alpha, insulin-like growth factor-1, c-myc,
      progesterone receptor and lactotransferrin reveals that, in general, the TGF beta
      transcript levels are regulated in a more transient manner by estrogen.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7819130
TI  - Characterization of platelet-derived growth factor alpha receptor synthesis and
      metabolic turnover.
AB  - Cellular responses to the AA isoform of platelet-derived growth factor (PDGF-AA)
      are mediated via the PDGF alpha receptor. Several studies suggest this receptor
      may signal pathways distinct from those activated by the PDGF beta receptor.
      Because alpha receptors are less well characterized than are beta receptors, and
      because the quantity of cell surface PDGF receptors governs the extent and
      perhaps type of PDGF-stimulated response, we examined the synthesis and
      degradation of alpha receptors in BALB/c-3T3 cells. Our data show that the ligand
      independent half-life of alpha receptors is 3 h and that optimal turnover of
      alpha receptors requires protein synthesis. In the presence of ligand, the half
      life of alpha receptors markedly decreases and is independent of protein
      synthesis. Although PDGF-AA accelerated the rate of alpha receptor turnover,
      pretreatment of cells with PDGF-AA and essentially complete down-regulation of
      alpha receptors did not correspondingly increase the level of alpha receptor
      synthesis. These findings indicate that the number of cell surface PDGF alpha
      receptors is regulated by the rate of internalization of these receptors. Lastly,
      we report that the recovery of PDGF-AA binding following down-regulation of alpha
      receptors is not affected by inhibition of RNA synthesis. Thus, repopulation of
      cell surface PDGF alpha receptors may not necessitate an increase in the level of
      PDGF alpha receptor mRNA.

PMID- 7819131
TI  - Cholesterol sulfate, a novel activator for the eta isoform of protein kinase C.
AB  - Activity of protein kinase C depends on the interaction with polar head-groups of
      two membrane lipids, i.e., phosphatidylserine and diacylglycerol. In the present
      study, we demonstrated a novel activation mechanism of the eta isoform of protein
      kinase C (nPKC eta), which is predominantly expressed in epithelial tissues in
      close association with epithelial differentiation. We found that the nPKC eta was
      activated by cholesterol sulfate, a metabolite of cholesterol formed during
      squamous differentiation. This activation was greater than that by
      phosphatidylserine plus phorbol ester; the Vmax for the activation by cholesterol
      sulfate was 3.6 times that by phosphatidylserine plus phorbol ester, while Kms
      were almost equal. In the presence of cholesterol sulfate, phorbol ester only
      weakly enhanced the activity of nPKC eta. Activation of nPKC eta by cholesterol
      sulfate was further demonstrated by autophosphorylation of the kinase molecule.
      However, the alpha and delta isoforms of protein kinase C were not activated by
      cholesterol sulfate. The present observation affords a new insight into a signal
      transduction pathway of squamous differentiation.

PMID- 7819132
TI  - Etoposide-induced differentiation of U937 promonocytic cells: AP-1-dependent gene
      expression and protein kinase C activation.
AB  - The administration of 150 nM etoposide, an inhibitor of DNA topoisomerase II
      activity, decreased the proliferation and induced the differentiation of U937
      human promonocytic cells, as determined by nitroblue tetrazolium reduction,
      surface accumulation of CD11b/CD18 and CD11c/CD18 integrins, and c-fms
      protooncogene expression. The expression of these differentiation markers started
      to be detected at 24 h of treatment. Etoposide caused little cell damage, as
      determined by trypan blue exclusion and by apoptotic-like DNA degradation, which
      was slightly initiated at 48 h. The treatment induced a transient increase in c
      fos, c-jun, and jun B mRNA levels, with maximum values at 12 h, a transient
      increase in collagenase mRNA level, with maximum value at 48 h, and a progressive
      increase in vimentin and lamin A and C mRNAs. These changes were qualitatively
      similar to those produced by 12-O-tetradecanoylphorbol-13-acetate. Etoposide also
      caused a transient increase of total AP-1 binding activity, with maximum value at
      12 h of treatment, as determined by gel retardation assays. The drug produced an
      early transient activation (3-6 h) of membrane-bound protein kinase C, followed
      by the later activation (48 h) of both the membrane and cytosolic enzyme. The
      protein kinase C inhibitors, sphinganine and 1-(5-isoquinolinylsulfonyl)-2
      methylpiperazine (H7), attenuated the induction of differentiation markers by
      etoposide. These results suggest that protein kinase C and AP-1-dependent gene
      expression could be involved in myeloid cell differentiation by DNA topoisomerase
      II inhibitors.

PMID- 7819133
TI  - Response of the phosphoenolpyruvate carboxykinase gene to glucocorticoids depends
      on the integrity of the cAMP pathway.
AB  - The phosphoenolpyruvate carboxykinase (PEPCK) gene is regulated at the
      transcriptional level by a variety of effectors in a tissue-specific fashion. In
      order to study the parameters involved in the tissue-specific hormonal regulation
      of the PEPCK gene, we have used a transient expression test in well
      differentiated rat hepatoma cells as well as in dedifferentiated variants. In
      this test, the PEPCK promoter is induced by glucocorticoids in well
      differentiated FGC4 cells, but not in H5 dedifferentiated variants, in spite of
      the presence in H5 cells of the glucocorticoid receptor. Study of the PEPCK
      promoter using electrophoretic mobility shift assays reveals binding sites for
      the liver-enriched transcription factors HNF1, vHNF1, HNF3, HNF4, and
      CAAT/enhancer binding protein members. Overexpression of the liver-enriched
      transcription factors absent in the dedifferentiated variants, such as HNF1 and
      HNF4, is not sufficient to restore glucocorticoid response of the PEPCK promoter
      in the variants. Moreover, systematic analysis of the PEPCK promoter reveals that
      the presence of a region covering a cAMP-responsive element (CRE1 at -80) and a
      CAAT box is necessary for full response of the PEPCK promoter to glucocorticoids
      in well-differentiated rat hepatoma cells. In a cotransfection test,
      overexpression of the regulatory subunit of protein kinase A (PKA), causing
      sequestering of PKA, abolishes the glucocorticoid response of the promoter in
      well-differentiated cells. On the other hand, in dedifferentiated variants,
      overexpression of the catalytic subunit of PKA restores the response to
      glucocorticoids. The action of PKA on the glucocorticoid response requires the
      presence of the CRE1 element and is promoter specific because it does not concern
      nonhepatic promoters such as the long terminal repeats of the mouse mammary tumor
      virus. These results suggest that the full response of the PEPCK promoter to
      glucocorticoids requires activation of another signal transduction pathway, the
      cAMP-mediated pathway.

PMID- 7819134
TI  - The enterocyte-like differentiation of the Caco-2 tumor cell line strongly
      correlates with responsiveness to cAMP and activation of kinase A pathway.
AB  - We have investigated the expression of protein kinase C (PKC) and protein kinase
      A (PKA) during the phases of growth and differentiation of the human colon
      carcinoma Caco-2 cells. We studied whether differentiation correlated with the
      responsiveness to cAMP and with an increased transport of the catalytic subunit
      of PKA into the nucleus. Also, we evaluated whether this phenomenon was affected
      by PKC activity. High levels of activated PKC were found in the plasma membranes
      of replicating cells. When the cells began to differentiate, plasma membrane
      activated PKC decreased, while the cytosolic fraction increased. On the contrary,
      PKA holoenzyme increased during differentiation, along with the transport of its
      catalytic subunit into the nucleus. Both types I and II kinase A holoenzymes
      increased during differentiation, with maximal type II activity found when cells
      were fully differentiated. In replicating preconfluent cells, the inhibition of
      PKC by high dose phorbol 12-myristate 13-acetate or sphingosine increased the
      amount of both PKA catalytic subunit in the nucleus and sucrase activity. During
      differentiation, 8-Bromo-cAMP increased PKA catalytic subunit in the nucleus and
      apoliprotein A1 mRNA levels. These effects were inhibited by low-dose phorbol 12
      myristate 13-acetate, which activates PKC in the plasma membranes. Our data
      suggest that PKC is activated in proliferating Caco-2 cells. The inhibition of
      PKC induces the transport of PKA catalytic subunit into the nucleus and the
      expression of the differentiation markers. Differentiated Caco-2 cells show a
      lower activation of PKC and an increased transport of the catalytic subunit of
      PKA into the nucleus.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7819135
TI  - Activation of interleukin-1 beta gene expression during retinoic acid-induced
      granulocytic differentiation of promyeloid leukemia cells.
AB  - We have examined the expression of the interleukin 1 beta (IL-1 beta) gene during
      the granulocytic differentiation of two promyeloid leukemia cell lines, HL-60 and
      NB4. HL-60 is known to differentiate along the granulocytic pathway after
      treatment with 13-trans-retinoic acid (13-trans-RA), whereas treatment with
      phorbol myristate acetate (PMA) leads to development of mature macrophages. NB4
      cells are derived from the bone marrow of an acute promyelocytic leukemia (APL)
      patient in relapse, have a translocated RA receptor-alpha, and are converted into
      nondividing granulocytes by 13-trans-RA treatment. When HL-60 or NB4 were
      cultured in the presence of 13-trans-RA, IL-1 beta mRNA and protein levels were
      increased. In the more mature THP-1 cells which are induced to macrophage-like
      cells by 13-trans-RA treatment, RA was unable to induce any IL-1 beta expression,
      implying that the effect of 13-trans-RA is associated with granulocytic
      differentiation. Moreover, PMA and 13-trans-RA had a strong synergistic effect in
      the induction of IL-1 beta gene expression. Nuclear run-off analysis indicated
      that the increased IL-1 beta gene expression was due to an enhanced rate of
      transcription. When the cells were transfected with an IL-1 beta-X-CAT reporter
      plasmid containing the -2982/-2748 promoter segment of the IL-1 beta gene
      conferring responsiveness to PMA, both NB4 and HL-60 cells responded with
      increased CAT activity when stimulated with 13-trans-RA alone. In contrast to
      PMA, 13-trans-RA was unable to increase AP-1 enhancer activity.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7819136
TI  - The role of cell cycle progression in cisplatin-induced apoptosis in Chinese
      hamster ovary cells.
AB  - Many anticancer drugs arrest cells in G2 of the cell cycle and subsequently
      induce cell death by apoptosis. The current experiments establish a detailed
      sequence of events that occur in Chinese hamster ovary CHO/UV41 cells following
      incubation with cisplatin. Synchronized CHO/UV41 cells were damaged with
      cisplatin in early S. The cells progressed at a normal rate through S but
      arrested in G2. The arrested cells exhibited normal levels of the mitosis
      promoting kinase p34cdc2 in its fully phosphorylated, inactive form. After a
      protracted arrest, the cells dephosphorylated p34cdc2 and underwent an aberrant
      mitosis and cytokinesis in which the chromosomes segregated unequally due to the
      formation of multipolar mitotic spindles. These cells subsequently lost contact
      with the extracellular matrix, and only then digested their DNA in a manner
      characteristic of apoptosis. This sequence of events could be dramatically
      accelerated by the addition of caffeine to G2-arrested cells, which induced
      dephosphorylation of p34cdc2 and passage through an aberrant mitosis. It has
      previously been suggested that protein synthesis is required for both caffeine
      induced premature mitosis and apoptosis. However, when added in G2, cycloheximide
      could inhibit neither the caffeine-induced mitosis nor apoptosis. Inhibition was
      only seen if cycloheximide was added during S before complete synthesis of the
      proteins required for mitosis. These results demonstrate that, in this model, the
      proteins thought to be involved in apoptosis are those required for normal cell
      cycle progression. It is hypothesized that the DNA digestion results from loss of
      signal transduction originating from the extracellular matrix but that earlier
      events leading to loss of cell adhesion are critical for the induction of
      apoptosis.

PMID- 7819137
TI  - Differential induction of apoptosis in human breast tumor cells by okadaic acid
      and related inhibitors of protein phosphatases 1 and 2A.
AB  - To investigate a possible relationship between apoptosis induction and protein
      phosphorylation in human breast carcinoma cells, we treated three such cell
      types, MB-231, MCF-7, and AU-565, with okadaic acid (OA), an inhibitor of protein
      phosphatases 1 and 2A, or phorbol 12 myristate 13-acetate, an activator of
      protein kinase C. We then examined these cells for the appearance of apoptosis
      markers. While OA caused multiplication arrest and cytotoxicity in all three cell
      lines, apoptosis was induced in MB-231 and MCF-7 cells but not in AU-565 cells. A
      similar cell-specific apoptosis induction was also observed after treatment with
      dinophysistoxin-1 (an active OA analogue) and with calyculin A (a structurally
      unrelated protein phosphatase inhibitor) but not with analogues that either are
      inactive or penetrate epithelial cells poorly. Phorbol 12-myristate 13-acetate
      also inhibited cell multiplication but was without effect in inducing apoptosis
      in these cells. Levels of the apoptosis-inhibitory protein BCL2 were examined in
      these cells, but they did not correlate with this differential susceptibility. We
      additionally treated the three cell types with 1-beta-D-arabinofuranosylcytosine
      and genistein to determine whether the AU-565 cell line would also be resistant
      to apoptosis induction by other chemical stimuli. Both of these agents led to the
      induction of apoptosis in all three cell lines. These results indicate that the
      AU-565 cells are specifically resistant to apoptosis induction by inhibitors of
      protein phosphatases 1 and 2A. This cell-specific resistance may thus allow one
      to identify cellular mediators of apoptosis by comparing protein phosphorylation
      patterns in these cells before and after treatment with OA or related inhibitors.

PMID- 7819138
TI  - Homing and in situ differentiation of resident pulmonary lymphocytes.
AB  - At birth, T lymphocytes which colonize the lung are mainly of the gamma delta
      subset, while alpha beta T cells predominate in the spleen. Thus, the lung is a
      preferred site for the homing of gamma delta T cells in the perinatal period.
      However, after birth, the pattern of V gamma gene usage among resident pulmonary
      lymphocytes (RPL) changes with age, from a predominance of V gamma 6 at birth to
      a predominance of V gamma 4 in older mice. The generation of the V gamma 6
      fraction appears to be thymus dependent, since in athymic nude mice, the V gamma
      6 population present at birth is replaced by V gamma 4 T cells. In the postnatal
      period, both RAG-1 and RAG-2 genes are expressed at high levels in the RPL
      population. TCR bearing cells are among those that express RAG genes, indicating
      that maturation of T cells takes place in this organ. In addition, transfer
      experiments reveal that lymphoid precursors are present in the lung. The stage of
      differentiation of these precursors will be characterized in future studies. The
      data presented here indicate that pulmonary T lymphocytes are derived from both
      migrants of thymic origin and from precursors which have undergone
      differentiation and selection in the lung. The population that is generated in
      situ and that has not been selected in the thymus may include cells that are
      typical for the pulmonary environment.

PMID- 7819139
TI  - Cis-acting DNA elements and cell type-specific nuclear proteins which may play a
      role in regulation of mouse CD8 alpha (Lyt-2) gene transcription.
AB  - Fusion of mouse CD8+ class I MHC-restricted T cells with the BW5147 thymoma
      invariably yields CD8- hybridomas in which RNA transcribed from the CD8 alpha
      (Lyt-2) gene is undetectable. To determine whether cis-acting DNA sequences may
      negatively regulate transcription of the Lyt-2 gene in BW5147 cells, one possible
      explanation for the above observation, BW5147 cells were stably transfected with
      the Lyt-2 gene containing 1 - 11,000 nucleotides of 5' flanking DNA and surface
      expression of Lyt-2 was monitored by flow microfluorometry. Initial results
      suggested the presence of a negative element between 1400 and 5000 nucleotides
      upstream of the site of transcription initiation. Further studies suggested the
      presence of two potential negative regulatory elements in this region, one of
      which includes a 269 nucleotide Accl - SstI fragment comprised of nucleotides 
      4700 to -4431 which bound nuclear proteins from CD8+ and CD8- cell lines in
      electrophoretic mobility shift assays (EMSA). EMSA studies performed using
      nuclear extracts from a variety of cell lines and tissues demonstrated that
      unique retarded complexes, called bands 1 and 2, correlated significantly with
      expression or non-expression of Lyt-2 respectively. EMSA analysis of proteins
      fractionated by SDS-PAGE from nuclear extract of the CD8+ VL3 T lymphoma cell
      line revealed proteins of approximately 110-130 kDa (called L2a-P1) and > 200 kDa
      (called L2a-P2) which bind within a 100 nucleotide region of this fragment
      (called L2a) to yield band 1 and 2 respectively, and which may play a role in
      regulation of Lyt-2 gene transcription.

PMID- 7819140
TI  - Involvement of 4F2 antigen expressed on the MHC-negative target cells in the
      recognition of murine CD3+CD4-CD8- alpha beta (V alpha 4/V beta 2) T cells.
AB  - T cells of an unique phenotype (CD3+CD4-CD8- alpha beta TCR+) develop in vitro
      from the hematopoietic progenitors, the majority of which carry homologous alpha
      beta TCR (V alpha 4J alpha 28/V beta 2D beta 1.1J beta 2.6). In the present
      study, antigen corresponding to the particular alpha beta TCR was investigated,
      taking advantage of the fact that growth of T cell hybridomas was arrested by
      their TCR stimulation. Results indicated that both syngeneic and allogeneic
      thymocytes, particularly from newborn mice, could specifically inhibit the
      proliferation of a T cell hybridoma with the V alpha 4/V beta 2 TCR (15H1.2).
      Proliferation of neither TCR-missing hybridoma subclones nor those with unrelated
      alpha beta TCRs was affected at all. It was also found that embryonal carcinoma
      (EC) cells without classical MHC antigens could specifically inhibit the
      proliferation of 15H1.2 cells. We then raised a mAb, 14.37, against an EC line,
      OTF9, that could interfere with the ability of them to inhibit the growth of
      15H1.2. Pretreatment of 15H1.2 cells with anti-V beta 2 and OTF9 cells with 14.37
      mAb respectively completely abrogated the growth inhibition of 15H1.2 by OTF9.
      The 14.37 antigen was a 120 kDa heterodimer glycoprotein consisting of 85 and 36
      kDa proteins. In normal lymphoid tissues, the expression of 14.37 antigen
      exhibited an apparently inverse relationship with that of class I MHC antigens.
      Thus, ontogenically it was strongly expressed in fetal and newborn mice, rather
      rapidly declined thereafter, and remained at very low levels in adult organs. In
      a given stage, the distribution of 14.37 antigen and class I MHC was rather
      exclusive to each other.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7819141
TI  - cAMP up-regulates IL-4 and IL-5 production from activated CD4+ T cells while
      decreasing IL-2 release and NF-AT induction.
AB  - Seven days after activation with concanavalin A and irradiated spleen cells,
      murine CD4+ T cells were re-stimulated with ionomycin and phorbol 12-myristate 13
      acetate (PMA). IL-2 and IL-4 were determined in the supernatant. When cholera
      toxin, forskolin together with phosphodiesterase inhibitors or dibutyryl-cAMP
      were added at the time of re-stimulation, a dose-dependent increase of IL-4 and
      IL-5 release was noted. IL-2 was down-regulated as reported before. The up
      regulation of IL-4 and the down-regulation of IL-2 correlated with an increase of
      IL-4 mRNA and a decrease of IL-2 mRNA as determined by semi-quantitative reverse
      transcriptase polymerase chain reaction. Similar results were found with
      prostaglandin E2 using PMA and ionomycin or plate-bound anti-CD3 antibody as re
      stimulants. These results suggest that, in activated CD4+ T cells, cAMP-elevating
      agents induce a switch of lymphokine production towards a Th2-like phenotype
      through regulation at the transcriptional level. This is supported by the fact
      that complex formation between a synthetic nuclear factor of activated T cells
      (NF-AT) binding site from the IL-2 promoter and nuclear extracts was decreased
      when cholera toxin was added to re-activated CD4+ T cells, suggesting that
      cholera toxin and cAMP down-regulate IL-2 expression via decreased NF-AT binding.
      Finally, since IL-4 has been reported to amplify IL-4 release from activated CD4+
      T cells, the autoinduction of IL-4 may very well function via cAMP.

PMID- 7819142
TI  - The role of the conserved residue in pocket A and the polymorphic residue in
      pocket E of HLA-B*3501 in presentation of human minor histocompatibility peptides
      to T cells.
AB  - We investigated T cell recognition for human minor histocompatibility (hmH)
      peptides using HLA-B*3501 restricted, hmH specific cytotoxic T lymphocytes (CTL)
      clones. These CTL clones killed C1R cells expressing HLA-B*3501 but not C1R cells
      expressing chimeric antigens between HLA-B*3501 and HLA-B*5101. They also failed
      to kill C1R cells expressing HLA-B*3501 mutants at residue 152 (B*3501-V152E) or
      at residue 171 (B*3501-Y171H). The CTL clone failed to kill C1R cells expressing
      these mutant molecules loaded with the hmH peptides isolated from C1R-B*3501
      cells although it killed a self-B cell line expressing HLA-B3501 loaded with the
      specific hmH peptides. The CTL clone also failed to kill T2 cells expressing the
      mutant molecules loaded with the specific peptides whereas it killed T2 cells
      expressing HLA-B*3501 loaded with the specific peptide. On the other hand,
      naturally occurring specific hmH peptides were isolated from purified B*3501
      V152E and B*3501-Y171H molecules, indicating that both HLA-B*3501-V152E and HLA
      B*3501-Y171H molecules can bind the hmH peptides. These findings indicate that
      both the conserved residue 171 in pocket A and the polymorphic residue 152 in
      pocket E are critical in recognition of the T cells but not binding of the hmH
      peptides. Furthermore, these results provide the possibility that the TCR
      recognizes a conformational structure of hmH peptides bound to HLA-B*3501
      molecules.

PMID- 7819143
TI  - The murine BP-3 gene encodes a relative of the CD38/NAD glycohydrolase family.
AB  - The murine BP-3 antigen is a variably glycosylated glycosyl-phosphatidylinositol
      (GPI)-linked molecule that is selectively expressed by early B and T lineage
      cells and a discrete subpopulation of reticular cells in the peripheral lymphoid
      organs. It is also expressed on the brush border of intestinal epithelial cells,
      the lumenal surface of renal collecting tubules and mature myeloid cells. To
      further explore the nature of the BP-3 antigen, we purified the protein, obtained
      peptide sequences and used these to isolate cDNA clones. Two BP-3 cDNA clones
      were found to share the same open reading frame, but to utilize different
      polyadenylation sites. Expression of a full-length cDNA clone confirmed that it
      encodes the BP-3 antigen. Northern blot analysis with this cDNA probe revealed BP
      3 transcripts of 1.3 and 2.3 kb in various tissues and cell lines representing
      myeloid, B and T cell lineages, while a probe containing the most 3' untranslated
      region of the longer cDNA clone hybridized only with the 2.3 kb RNA species.
      Analysis of the BP-3 cDNA sequence indicates that it represents a previously
      undescribed gene that shares significant homology with genes encoding
      nicotinamide adenine dinucleotide (NAD) glycohydrolase of Aplysia californica and
      the CD38 antigens in mouse and human. However, cells expressing the recombinant
      BP-3 protein did not exhibit NADase activity, suggesting that it may be a distant
      relative of NAD hydrolase with different function.

PMID- 7819144
TI  - Alternative complement pathway activation by CD4+ T cells of HIV infected
      individuals: a possible role in AIDS pathogenesis.
AB  - The mechanisms by which CD4+ T cells are eliminated during HIV infection are
      poorly understood. We have previously shown that HIV infected cell lines activate
      and fix C3 via the alternative complement pathway (ACP). In the present study we
      examined the ability of blood lymphocytes from 40 HIV+ individuals to fix C3. A
      large fraction of the CD4+ T cells reacted with anti-gp120 antibodies. These
      cells also carried C3 fragments in vivo and could further fix C3 if exposed to
      human serum in vitro. C3 activation occurred via the ACP. In some cases exposure
      of the lymphocytes to human serum under conditions allowing ACP activation
      resulted in partial elimination of CD4+ T cells. The results suggest that
      complement activation and fixation by CD4+ T cells opsonized with HIV particles
      or gp120 may contribute to their selective destruction.

PMID- 7819145
TI  - Preferential TCR V usage in rat repertoire selection: V alpha 8 imparts both
      positive thymic selection by and alloreactivity to RT1f.
AB  - Using a panel of newly developed mAb to two rat TCR V alpha and four TCR V beta
      segments, TCR V usage in CD4 and CD8 T cells of eight RT1 congenic strains
      sharing the LEW background was analyzed by flow cytometry. While no striking
      effects on V beta 8.2 and 8.5 usage were observed, a 3- to 4-fold over
      representation of V beta 10 in the CD4 as compared with the CD8 subset in all
      strains suggested a preference of V beta 10 for MHC class II products. The degree
      of 'overselection' was mapped to the RT1.B/D region. In addition, an allele
      specific overselection of V alpha 4+ CD4 T cells was mapped to RT1.B/Du and of V
      beta 16+ CD8 T cells to RT1.Au. Finally, a dramatic overselection of V alpha 8+
      CD8 T cells by RT1f (14% in RT1f versus 1-2% in other haplotypes) provides the
      most striking case yet for an intrinsic affinity of a TCR V segment for an MHC
      product. V alpha 8+ CD8 T cells are not only overselected by RT1f in the thymus,
      but also during the alloreactive response of peripheral CD8 T cells to RT1f. The
      implications of these findings for the contribution of TCR V segments to TCR-MHC
      interactions in repertoire selection and alloreactivity are discussed.

PMID- 7819146
TI  - Different types of in vivo induced cytolytic T lymphocytes are all LFA-Ihigh and
      lack CD45 exon 4 (CD45RA) but show distinct CD45RC profiles.
AB  - Due to alternate mRNA splicing of exons 4, 5 and 6 (or A, B and C respectively),
      the CD45 cell surface glycoprotein is structurally heterogeneic in lymphoid cells
      of different lineage or stage of activation. Previous studies show that in vivo
      induced allo- and superantigen reactive rat cytolytic T lymphocytes (CTL)
      preferably belong to the CD45RClow subset, whereas tumour selective CTL express
      high amounts of CD45RC cell surface molecules. In this paper, reverse
      transcription polymerase chain reaction technique (RT-PCR) was utilized to
      evaluate CD45 isoform expression of rat lymphoid cells and in vivo activated rat
      CTL with distinct specificity and CD45RC profile. Cells from lymphoid organs
      expressed six CD45 mRNA isoforms, exon(45678), exon(5678), exon (578), exon(678),
      exon(78) and a novel extensively spliced exon(8) variant. In vivo activated TCR
      alpha beta + CD8+ cells sorted as CD45RClow expressed exon(78), exon(578) and
      exon(8), whereas TCR alpha beta + CD8+CD45RChigh cells expressed exon(78),
      exon(578), exon(5678) and full-length exon(45678). Triple-colour staining
      indicated high expression of LFA-1 in the cytotoxic CD45RCintermediate and
      CD45RClow cells, and low expression of LFA-1 in CD45RChigh non-cytotoxic cells
      from allo- and superantigen activated rats. In contrast, tumour activated TCR
      alpha beta +CD45RChigh cells were divided in LFA-1high and LFA-1low subsets, and
      sorting of these subsets revealed that tumour-selective cytotoxicity was confined
      to the LFA-1high effector cell subset. Furthermore, it was evident that the LFA
      1high effector cell subset expressed high levels of exon(5678), exon(578) and
      exon(78) isoforms and, in contrast to the LFA-1low subpopulation, lacked
      expression of exon 4 containing full-length CD45 mRNA transcript.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7819147
TI  - Specificity of signal transduction through CD16, TCR-CD3 and BCR receptor chains
      containing the tyrosine-associated activation motif.
AB  - FcR gamma III (CD16) is a member of a family of receptor proteins that bind to Fc
      regions of IgG molecules. Ligation of CD16 transduces signal and alters tyrosine
      phosphorylation of proteins in natural killer, B and T cells. However, the
      identity of protein tyrosine kinases (PTKs) involved in CD16 signaling and the
      mode of their interaction with the receptor are not completely understood. Here,
      we show that the transmembrane form of CD16 transfected in a CD3- Jurkat cell
      line associates with p56lck and ZAP-70 PTKs. Using chimeric proteins consisting
      of the extracellular domain of CD16 and the cytoplasmic portions of the zeta
      chain, we find that these PTKs interact with the 17-residue activation motif
      present in the zeta chain. Substitution of tyrosine residues in the motif with
      phenylalanine blocks the interaction of PTKs and abrogates signal transduction.
      Comparative studies demonstrate that similar to zeta, MB1 protein of the IgM
      receptor also binds to p56lck and ZAP-70 in T cells and induces strong activation
      responses, whereas CD3 gamma, delta and epsilon chains do not interact with ZAP
      70 and transduce weak signals. Together, these results demonstrate that: (i) PTKs
      bound to CD16 mediate signal transduction, (ii) ZAP-70 plays a crucial role in
      signaling and (iii) apart from tyrosine residues in the activation motif, other
      structural constraints also regulate the interaction of PTKs with the receptor
      molecule.

PMID- 7819148
TI  - Maturation of medullary thymic epithelium requires thymocytes expressing fully
      assembled CD3-TCR complexes.
AB  - Unlike medullary thymic epithelial cells (TEC) of normal mice, medullary TEC of
      TCR- SCID mice are immature and disorganized. In order to assess directly the
      role of TCR+ cells in the development of medullary TEC, we bred mice which co
      expressed the SCID genetic defect and transgenes encoding clonotypic TCR chains.
      Immunohistologic examination revealed that medullary thymic epithelial cells from
      TCR beta transgenic SCID mice, whose thymocytes only express TCR beta chains that
      inefficiently associate with CD3 and zeta components, remained immature and
      disorganized. In contrast, medullary TEC from TCR alpha beta transgenic SCID
      mice, whose thymocytes express fully assembled CD3-zeta-TCR alpha beta complexes
      were mature and organized. Interestingly, the ability of TCR alpha beta(+)
      zeta(+)-CD3+ thymocytes to induce maturation of medullary TEC appeared not to be
      related to the antigen specificity of the TCR as thymi from positively selecting,
      negatively selecting and non-selecting TCR alpha beta transgenic SCID mice all
      possessed induced medullary thymic epithelial cells. In addition, we found that
      induction of medullary TEC cells was associated with the presence of medullary
      thymocytes, including those of the CD4-CD8- TCR alpha beta+ phenotype. The
      present findings demonstrate that fully assembled CD3-zeta-TCR complexes are
      required to induce maturation of medullary thymic epithelial cells and indicate
      that thymocyte induction of medullary thymic epithelial cells may result from
      signaling independently of their clonotypic TCR chains.

PMID- 7819149
TI  - MHC class II hierarchy of superantigen presentation predicts efficiency of
      infection with mouse mammary tumor virus.
AB  - Superantigens (SAgs) encoded by infectious mouse mammary tumor viruses (MMTVs)
      play a crucial role in the viral life cycle. Their expression by infected B cells
      induces a proliferative immune response by SAg-reactive T cells which amplifies
      MMTV infection. This response most likely ensures stable MMTV infection and
      transmission to the mammary gland. Since T cell reactivity to SAgs from
      endogenous Mtv loci depends on MHC class II molecules expressed by B cells, we
      have determined the ability of MMTV to infect various MHC congenic mice. We show
      that MHC class II I-E+ compared with I-E- mouse strains show higher levels of
      MMTV infection, most likely due to their ability to induce a vigorous SAg
      dependent immune response following MMTV encounter. Inefficient infection is
      observed in MHC class II I-E- mice, which have been shown to present endogenous
      SAgs poorly. Therefore, during MMTV infection the differential ability of MHC
      class II molecules to form a functional complex with SAg determines the magnitude
      of the proliferative response of SAg-reactive T cells. This in turn influences
      the degree of T cell help provided to infected B cells and therefore the
      efficiency of amplification of MMTV infection.

PMID- 7819150
TI  - O-acetyl GD3 ganglioside in human peripheral blood T lymphocytes.
AB  - O-acetyl GD3 ganglioside is a cell surface molecule of some neural, neural crest
      and renal cells. Here we show, by using mAbs specific for O-acetyl GD3 (clone
      27A) and flow-cytometric, biochemical or immunological techniques, that it is
      also expressed at high intensity level on the surface of 49.6% (median) of the
      CD3+ cells (T lymphocytes), at medium level in 16.2% of the CD16+ (natural
      killer) cells, at very low level in 51.9% of CD14+ cells (monocytes) and in 6.9%
      of CD20+ cells (B lymphocytes), but not in other human blood cells. Of the CD4+
      or CD8+ cells, 52.6 or 36.5% respectively were 27A+. Furthermore, 81.6% of the
      CD45RO+ lymphocytes carried the O-acetyl GD3 ganglioside. It was not detected in
      the thymus, although its immediate precursor, the GD3 ganglioside, was present in
      the medullary thymocytes, suggesting that O-acetyltransferases are regulated by
      maturation events taking place in the periphery. The anti-O-acetyl GD3 antibodies
      induced a strong mitogenic response in cultured peripheral blood mononuclear
      cells, but not in purified T cells. However, in combination with phorbol
      myristate acetate the antibodies induced proliferation also in purified T cells,
      suggesting that protein kinase C priming is needed for this effect. This and the
      restricted expression of O-acetyl GD3 suggest a functional role for this
      ganglioside in T cell subpopulations.

PMID- 7819151
TI  - Censoring of self-reactive B cells with a range of receptor affinities in
      transgenic mice expressing heavy chains for a lysozyme-specific antibody.
AB  - Transgenic mice carrying a rearranged Ig gene encoding the H chain of a lysozyme
      specific antibody were used to examine the effect of antigen binding affinity on
      elimination of self-reactive B cells. In H chain transgenic mice, B cells
      expressed surface IgM and IgD composed of lysozyme-specific H chains and many
      different possible L chains from endogenous L chain genes. Immunofluorescent
      staining and flow cytometry revealed a distinct subset comprising approximately
      1% of spleen B cells that bound lysozyme with a high affinity comparable with the
      original lysozyme-specific antibody. Additional subsets accounting for a total of
      5-6% of spleen B cells bound lysozyme more weakly, with the weakest requiring
      10,000-fold higher concentrations of monomeric hen egg lysozyme to attain 50%
      receptor saturation. When the various B cell subpopulations were allowed to
      develop in animals expressing lysozyme as a membrane-bound antigen on autologous
      cells, both low and high affinity lysozyme-binding B cells were undetectable in
      peripheral lymphoid organs. These findings demonstrate the efficacy with which
      low affinity self-reactive B cells can be eliminated in vivo, consistent with the
      notion that this cellular mechanism accounts for the absence of natural IgM
      antibodies against self antigens on the surface of blood cells. The data also
      illustrate the potential use of Ig transgenic mice for analyzing and selecting
      novel receptor-ligand interactions.

PMID- 7819152
TI  - Mechanisms that limit the diversity of antibodies. II. Evolutionary conservation
      of Ig variable region genes which encode naturally occurring autoantibodies.
AB  - Antibody which reacts with phosphatidyl choline can be detected in all normal
      mice. Generation of this specificity requires the use of either the unmutated
      VH11 or VH12 genes, with constraints on the length and sequence of CDR3, and
      specific light chain association. Given that those parts of the antibody that are
      subject to somatically generated diversity are restricted, we hypothesized that
      the germline VH11 and VH12 genes may be evolutionarily conserved to a greater
      extent than other VH genes. The nucleotide sequence was determined from a panel
      of inbred strains and Mus species for VH11 and VH12. The results were compared to
      the three functional members of the S107 VH family and show that VH11 and VH12
      have a total of 13 silent and three replacement mutations while the S107 genes
      have 11 silent and 20 replacement mutations. This implies that there has been
      strong selection to conserve the VH11 and VH12 gene products, which must reflect
      a substantial survival value to the individual. Sequence comparisons also show
      that the alleles present in the recently derived inbred strains arose prior to
      speciation. While there is polymorphism within the inbred strains, there are
      alleles which are shared between species which diverged 3-5 million years ago.
      Conservation at the amino acid and nucleotide levels argues against the idea that
      Ig genes evolve at a rapid rate and suggests that the rate at which mutations are
      incorporated may be determined by the importance of the encoded protein.

PMID- 7819153
TI  - Bias in somatic hypermutation of human VH genes.
AB  - Translationally silent mutations, which are not antigen selected, of human VH6 Ig
      gene rearrangements isolated from human spleen were analyzed for bias to gain
      insight into intrinsic features of the mutation process. Sixty-three clones
      representing 38 VH6DJ rearrangements had an overall mutation frequency of 4.5%, a
      replacement/silent (R/S) mutation ratio of 2.1 and 167 unique silent mutations.
      The silent mutations showed bias in: (i) targeting to CDR1 and CDR2, (ii) an
      increased frequency of mutations of A compared to T nucleotide bases on the
      coding strand, and (iii) an increased frequency of transitions versus
      transversions. Bias of C-->G over C-->A, of G-->C over G-->T and of A-->C over A-
      >T transversions was also present. Hot spots of mutation were observed, some
      which corresponded to potential sites of stem-loop formation. The results suggest
      that the somatic mutation process in man may be targeted to the complementarity
      determining region for some V genes, exhibits specific base substitutions
      favoring transitions and specific types of transversions, and may be occurring on
      only one DNA strand.

PMID- 7819154
TI  - Prevention of insulitis and diabetes in beta 2-microglobulin-deficient non-obese
      diabetic mice.
AB  - beta 2-Microglobulin (beta 2m)-deficient non-obese diabetic (NOD) mice were
      established by crossing beta 2m-deficient 129/Sv mice with NOD mice, and used to
      examine the possible involvement of MHC class I molecules and CD8+ T cells in the
      development of insulitis and diabetes. In these mice, MHC class I molecules were
      not expressed, resulting in no generation of CD8+ T cells. None of eight lines of
      beta 2m-deficient NOD mice (-/-) established developed overt diabetes by 32
      weeks, while control littermates (+/+) became diabetic by 22 weeks. histological
      studies showed no significant lymphocyte infiltration of the islets (insulitis
      score: 0.03 +/- 0.03) in any of the beta 2m-deficient NOD mice (-/-) compared
      with littermate NOD mice (+/+) with overt insulitis (1.42 +/- 0.28). These
      findings support the notion that the expression of MHC class I molecules and/or
      CD8+ T cells plays an essential role in the infiltration of CD4+ T cells in
      islets as well as the development of diabetes in NOD mice.

PMID- 7819155
TI  - Implication of the common gamma chain of the IL-7 receptor in intrathymic
      development of pro-T cells.
AB  - The effects of IL-7 on the growth and differentiation of thymocytes were analyzed
      using murine fetal thymus organ cultures (FTOC) in the presence of mAbs specific
      for the conventional IL-7 receptor (IL-7R) and for the common gamma (gamma c)
      chain. In FTOC, the development of CD4-CD8- double-negative thymocytes to
      CD4+CD8+ double-positive (DP) and CD4+ or CD8+ single-positive (SP) cells was not
      completely blocked by adding these mAbs, although cell growth was reduced by the
      treatment. To define a developing stage sensitive to the mAbs, most immature
      thymocytes, Pgp-1+ c-kit+ cells, were cultured in 2-deoxyguanosine treated fetal
      thymus. In the presence of both mAbs in the culture, neither DP nor SP thymocytes
      developed whereas either of the mAbs partially blocked their development. These
      results indicate that the gamma c chain is involved in early T cell development
      as an indispensable subunit of the functional IL-7 receptor complex.

PMID- 7819156
TI  - "Iso-depth contour map" of a molecular surface.
AB  - The representation and display of protein surfaces are useful in many areas of
      molecular modeling, and surface shape study is particularly important in the
      analysis of protein-ligand interactions. We introduce here the notion of the
      molecular surface convex hull, allowing the depth of any molecular surface point
      to be defined. A two-dimensional (2D) map, the iso-depth contour map, and a three
      dimensional (3D) representation, the iso-depth lines, allow the topography of a
      molecular surface to be displayed in terms of knobs (high depth) and holes (low
      depth).

PMID- 7819157
TI  - Calculated surface electrostatic potentials of molecular sieve models containing
      SiO4, AlO4, and PO4 units.
AB  - Surface electrostatic potentials have been computed at the ab initio HF/STO-5G*
      level for two model systems: a fragment of a zeolite channel wall; and a fragment
      composed of SiO4, AlO4 and PO4 units. The potential above the SiO4 network is
      negative everywhere, despite these units commonly being regarded as electrically
      neutral. In marked contrast, the AlO4 and PO4 units introduce strongly negative
      and positive regions, respectively, giving rise to a much more heterogeneous
      surface potential.

PMID- 7819158
TI  - NanoVision--molecular graphics for the Macintosh.
AB  - NanoVision is a molecular graphics program for the Apple Macintosh. The program
      follows accepted Macintosh design criteria, making it easy to learn by anyone
      familiar with the Macintosh. Molecules containing up to 32,000 atoms may be
      displayed. The program includes a range of molecular display options, including
      skeletal, ball-and-stick, and CPK. Images may be displayed using up to 240
      colors. Color depth cuing is provided, as is Z-clipping. NanoVision images may be
      easily transferred (cut and paste) to drawing programs.

PMID- 7819159
TI  - DNurbs: DNA modeled with NURBS.
AB  - DNurbs (dee-in-urbs) are a small number of bicubic patches wrapping each base
      pair in complementary DNA. NURBS, the nonuniform rational B-spline surfaces now
      popular in computer graphics, are employed for the patches. Control points for
      the surface patches are generated from the molecular surface based on canonical
      base pairs.

PMID- 7819160
TI  - Modeling cytochrome P450 14 alpha demethylase (Candida albicans) from P450cam.
AB  - The tertiary structure of cytochrome P450 14 alpha demethylase--Candida albicans
      (P450 CA) is modeled on the basis of sequence alignment with two closely related
      proteins and the crystallographic structure of Pseudomonas putida P450cam. The
      secondary structure prediction system used combines the information from several
      algorithms and trains the data to offer an optimized prediction of the known
      P450cam. The trained algorithm was then used to predict the secondary structure
      of the other P450 sequences. The prediction of the surface coil regions was aided
      by an alignment between P450 CA and the homologous sequences P450 14 alpha
      demethylase--Saccharomyces cerevisiae (66 SD) and P450 14 alpha demethylase-
      Candida tropicalis (72 SD). The prediction and alignment information was combined
      to establish an alignment between P450 CA and P450cam, and to assign full
      secondary structure to the target protein. This secondary structure was folded
      from the template of P450cam and the predicted structure was relaxed by molecular
      dynamics. Model checking highlighted minor adjustments in the alignment,
      correctly orienting hydrophobic and hydrophilic side chains. The model offers
      explanations for several known experimental results and suggests further
      investigations that may prove fruitful in understanding the structure and
      mechanisms of the P450 family (Porter, T.D. and Coon, M.J. Minireview cytochrome
      P450. J. Biol. Chem. 1991, 266, 13469-13472. Waterman, M.R. Cytochrome P450
      cellular distribution and structural considerations. Current Opinion in
      Structural Biology 1992, 2, 384-387. Aoyama, Y., Yoshida, Y., Sonohdo, Y. and
      Sato, Y. Structural analysis of the interaction between the side-chain of
      substrates and the active site of lanosterol 14 alpha demethylase (P450 14DM) of
      yeast. Biochim. Biophys. Acta 1992, 1122, 251-255.).

PMID- 7819161
TI  - Usefulness of one electron properties in the study of the nitromethane-to-methyl
      nitrite rearrangement.
AB  - Large-scale multiple reference configuration interaction calculations for a
      unimolecular rearrangement reaction of nitromethane to methyl nitrite are
      presented. The complicated structure of potential energy curves is explained in
      terms of interactions between ground and excited states. An explanation for an
      extremely long C--N and C--O bond distances in the transition state is also
      given. The study of corresponding dipole moments and electrostatic molecular
      potentials enhances the overall understanding of the reaction.

PMID- 7819162
TI  - WinMGM: a fast CPK molecular graphics program for analyzing molecular structure.
AB  - A molecular modeling program is presented which has been written for Microsoft
      windows 3.1 and Windows NT operating systems. The program permits interactive
      molecular manipulation and also provides analytical tools such as energy
      computations and solvent accessible surfaces. An extremely fast algorithm is used
      which generates realistic space-filling CPK images in addition to wire frame,
      ribbons, MIDAS, labels, and points. An important feature of this algorithm is a
      highly optimized Z-buffer, which is described.

PMID- 7819163
TI  - Polymer chain packing analysis using molecular modeling.
AB  - This article describes the methodology used in applying molecular modeling to
      investigate the chain packing of polymers. Models for polyethylene and trans
      polyacetylene were developed in order to study the cell packing energy as a
      function of the chain setting angles. This approach was found to yield chain
      setting angle values that corresponded to those determined experimentally by
      other authors. The limitations of the method are also discussed.

PMID- 7819164
TI  - EyeChem 1.0: a modular chemistry toolkit for collaborative molecular
      visualization.
AB  - EyeChem is a network-aware and modular molecular visualization toolkit used
      within the Iris Explorer Visualization program. Use of the toolkit is illustrated
      via four typical EyeChem applications, which consist of Explorer maps constructed
      from chemically oriented modules and developed for use over the new generation of
      fast networks such as the UK SuperJanet system. EyeChem can also be used to
      prepare multimedia style visualizations in Quicktime or MPEG format of molecular
      properties and wavefunctions for archiving via the gopher+ wide area information
      system. The use of such information in electronic publishing of chemical
      information is discussed.

PMID- 7819165
TI  - MacMolecular: a program for visualization of molecular structures on the
      Macintosh.
AB  - MacMolecular displays small- to medium-sized biomolecules, with particular
      emphasis on peptides. It has been developed to run on color Macintosh computers.
      The display can be stick, ball and stick, depth cued by thickness stick, or
      several types of space-filling representations. The program takes input from
      standard PDB files, simple Cartesian coordinate files, and, in addition, from
      Kinemage files in which atom information has been included. The program allows
      color changes of various types as well as the normal functions of translation,
      rotation, and zooming. In addition, animation files may be produced for
      subsequent display. Bonding of atoms is done by a distance algorithm (standard)
      or sequentially to properly display C alpha traces and traces of peptides
      containing simplified representations of amino acids. Stereo viewing is
      available, and manipulated structures which were drawn from PDB files can be
      written out to new PDB files. In addition, PICT files of the drawing window can
      be generated.

PMID- 7819166
TI  - The role of cytokines in ocular inflammation.

PMID- 7819167
TI  - Thromboxane in ocular pathophysiology.

PMID- 7819168
TI  - Factors affecting the success rate of open lacrimal surgery.
AB  - Postoperative soft tissue infection may predispose to failure of open lacrimal
      surgical procedures. Using a retrospective analysis of 413 cases, the failure
      rates for primary and repeat surgery were 12.0% and 8.9% respectively (0.25 < p <
      0.5). Postoperative soft tissue infection is associated with an increased risk of
      failure (p < 0.005); antibiotics decrease the rate of postoperative infection and
      may thus decrease the failure rate. Furthermore, antibiotic therapy decreases the
      rate of failure in cases after previous facial trauma. Curative antibiotic
      therapy for established postoperative infection is less effective than
      preventative therapy at improving the success rate after surgery. Previous trauma
      is also associated with a greater rate of failure (p < 0.02), possibly owing to
      the frequent canalicular problems in such patients. Silicone tubes appear to
      increase neither the rate of infection nor failure (p > 0.5). Trauma, acute
      dacryocystitis, and silicone tubes appear to act on outcome independently of each
      other.

PMID- 7819169
TI  - Long-term results after probing for congenital nasolacrimal duct obstruction.
AB  - The long term results of probing for congenital nasolacrimal duct obstruction
      were reviewed using a parental questionnaire issued to both treated and age
      matched control groups. On follow up 4-13 years after probing in childhood 30% of
      patients still had symptoms of epiphora or discharge. Surprisingly, a similar
      high symptom rate was found in the controls, such that there was no statistically
      significant difference in the rate of symptoms between the two groups. Probing
      had therefore apparently reduced the symptom rate to a level close to normal for
      the age group concerned. All studies on the incidence of congenital nasolacrimal
      duct obstruction must be interpreted with reference to the known high rate of
      spontaneous resolution as a clear trend has been demonstrated towards a lower
      incidence of symptoms the longer the follow up after probing. This finding would
      support a policy of delay before further intervention in patients with mild
      residual symptoms after a technically successful probing.

PMID- 7819170
TI  - Clinical comparison of the ProTon and Tono-Pen tonometers with the Goldmann
      applanation tonometer.
AB  - A clinical evaluation of a new electron ProTon tonometer was performed comparing
      the values of intraocular pressure (IOP) measured using this instrument with
      those determined by a similar instrument, Tono-Pen XL, and by Goldmann
      applanation tonometry. The mean IOP measured in 106 eyes with the ProTon
      tonometer was not significantly different from that determined with Goldmann
      applanation, while the IOP values measured with Tono-Pen XL were significantly
      lower. The 95% limits of agreement between applanation tonometry and ProTon
      tonometry were between -4 mm Hg and 5 mm Hg and between applanation tonometry and
      Tono-Pen XL tonometry between -3 mm Hg and 8 mm Hg. The ProTon tonometer appears
      to have a higher level of accuracy than the Tono-Pen XL tonometer in clinical
      practice.

PMID- 7819171
TI  - Additive effect of latanoprost, a prostaglandin F2 alpha analogue, and timolol in
      patients with elevated intraocular pressure.
AB  - A randomised observer masked clinical study was conducted to assess the additive
      effect of latanoprost (13,14-dihydro-17-phenyl-18,19,20-trinorprostaglandin F2
      alpha-isopropylester) to timolol maleate in patients with elevated intraocular
      pressure (IOP). Patients were randomly assigned to two treatment groups. One
      group (n = 10) received timolol, the other group (n = 9) received latanoprost
      twice daily for 1 week. After 1 week all patients received both timolol and
      latanoprost. Eyes treated with timolol (mean diurnal IOP (SD) day 0, 24.2 (2.8)
      mm Hg) and latanoprost (mean diurnal IOP day 0, 28.5 (5.6) mm Hg) showed an IOP
      reduction of 5.9 (2.3) mm Hg (24%) and 8.9 (2.5) mm Hg (31%), respectively after
      the first week. Adding latanoprost to the eyes treated with timolol as well as
      timolol to the eyes receiving latanoprost gave a further reduction of 2.6 (1.1)
      mm Hg (13%) and 2.6 (2.2) mm Hg (14%), respectively. Only mild transient
      hyperaemia was observed in patients receiving latanoprost. The results indicate
      that latanoprost and timolol can be combined successfully and that complete or
      almost complete additivity is reached even at pressure levels below 20 mm Hg.

PMID- 7819172
TI  - John Martin Wheeler, 1879-1938.

PMID- 7819173
TI  - Myopic shift and its mechanism in nephropathia epidemica or Puumala virus
      infection.
AB  - Nephropathia epidemica (NE) is a zoonose caused by Puumala virus. NE belongs to
      the group of haemorrhagic fevers with renal syndrome. Transient myopia has been
      described in the acute phase of the disease. This prospective study presents the
      changes of refraction and the results of ophthalmic A scan measurements of
      patients who were managed at Savonlinna Central Hospital for NE during an
      epidemic in the winter of 1992-3. This involved 37 patients and 74 eyes. The
      incidence of transient myopia was 8.1% and that of myopic shift 40.5%. A scan
      ultrasound measurements were performed in patients in the acute phase and after
      total recovery of their general illness. Statistical analysis revealed that there
      were significant differences in anterior chamber depth and lens thickness between
      the acute and control phases of the disease and between the patients who had
      myopic shift compared with those who did not have a significant myopic change in
      refraction. Based on these results it seems that the reason for transient myopic
      shift of NE is mainly a combination of two factors: forward movement of the
      anterior diaphragm and thickening of the crystalline lens. The term myopic shift
      should be used rather than transient myopia because it better describes the
      overall refractive change in NE.

PMID- 7819174
TI  - Extended wear soft contact lenses induce corneal epithelial changes.
AB  - The purpose of this study was to determine the corneal epithelial alterations
      induced by various types of contact lenses. By employing the specular microscope,
      the corneal epithelia of 60 patients who had worn contact lenses for more than 1
      year were re-examined along with 15 myopic controls. The morphological changes in
      aphakic patients who changed from extended wear soft to extended wear rigid gas
      permeable lenses were also studied. The mean cell area of the corneal epithelium
      was 621.5 (SD 92.5) microns 2 for daily wear rigid gas permeable lenses (n = 15),
      645.8 (98.1) microns 2 for daily wear soft lenses (n = 15), and 634.7 (88.6)
      microns 2 for extended wear rigid gas permeable lenses (n = 15), none of which
      differed significantly from the control value of 610.5 (98.1) microns 2. Only the
      extended wear soft lens group (n = 15) showed significantly enlarged epithelia
      (806.1 (50.1) microns 2, p < 0.01 versus the other groups). The epithelium
      partially returned to normal after changing from extended wear soft lenses to
      extended wear rigid gas permeable ones. The corneal epithelium showed increased
      cell area only with extended wear soft contact lenses which are known to pose a
      risk for corneal infection.

PMID- 7819175
TI  - Vestibulo-ocular reflex abnormality in Vogt-Koyanagi-Harada syndrome.
AB  - The eye movements of 15 patients with Vogt-Koyanagi-Harada (VKH) syndrome were
      analysed. Transient dizziness occurred in 60% of the patients. Eight patients
      (53%) exhibited horizontal jerk nystagmus that was completely inhibited by visual
      fixation. Eight cases (53%) exhibited the elevation of vestibulo-ocular reflex
      (VOR) gain in darkness. Six of the patients with nystagmus had defective smooth
      pursuit movements with reduced gain on the side ipsilateral to the nystagmus.
      Saccadic and optokinetic eye movements were intact, and visual vestibular
      interaction was also normal. Impaired eye movements in VKH syndrome may be caused
      by asymmetry of the vestibular function secondary to the labyrinthine
      inflammation.

PMID- 7819176
TI  - Effect of interleukin 1 receptor antagonist on the blood-aqueous barrier after
      intraocular lens implantation.
AB  - Interleukin 1 (IL-1) possesses as an intercellular signal a wide spectrum of
      inflammatory, metabolic, haematopoetic, immunological, and reparative properties
      and can be a mediator not only of host defence but also of disease. Reduction of
      IL-1 can decrease the inflammatory host response. A human recombinant IL-1
      receptor antagonist (IL-1ra) was used to block IL-1 after intraocular lens
      implantation in rabbits. Seventeen rabbits underwent intercapsular
      phacoemulsification and posterior chamber lens implantation. A 100 micrograms
      dose (0.1 ml) of IL-1ra (1 mg/ml) was injected into the anterior chamber at the
      end of surgery in seven rabbits. The 10 rabbits serving as the controls received
      no IL-1ra. Postoperatively, all rabbits were observed with a slit-lamp, and the
      aqueous flare intensity was measured with a laser flare cell meter at 12 hours,
      1, 2, 3, and 4 days and thereafter at 1, 2, 3, and 4 weeks. Aqueous flare
      intensity was significantly lower on days 2 and 3, and fibrin deposition much
      less marked in the eyes treated with IL-1ra, compared with the controls. The
      results suggest that IL-1 is involved in the postoperative inflammation that
      occurs after intraocular lens implantation and the use of the IL-1ra would be
      valuable for reducing this problem.

PMID- 7819177
TI  - Localisation of thromboxane A2 receptors and the corresponding mRNAs in human eye
      tissue.
AB  - Thromboxane A2 (TxA2) receptors in human eye sections were identified and
      localised using a potent TxA2 specific agonist, 125-iodinated 5-heptenoic acid 7
      [3-[3-hydroxy-4-[4-(iodo-125I) phenoxy]-1-butenyl]-7- oxabicyclo[2.2.1]hept-2-yl]
      ,[1S-[1a,2a,(Z),3B(1E,3S*),4a]]-C23 H29 IO5 (125I-BOP) in a binding assay. TxA2
      receptors were concentrated in several specific loci within ocular tissues,
      including the corneal epithelium, the ciliary processes, retina, and posterior
      ciliary arteries. In addition, we have used the method of in situ hybridisation
      to observe the distribution of TxA2 receptor mRNA. The distributions of both
      receptor binding sites and receptor mRNAs showed a close correlation. These
      studies employed film autoradiography which does not permit cellular resolution.
      In order to obtain enhanced cellular resolution and more detailed information
      about the localisation of the receptors and their corresponding mRNAs, emulsion
      autoradiography was used after ligand binding and in situ hybridisation. This
      approach showed further that TxA2 receptors are mainly concentrated on non
      pigmented epithelial cells of the ciliary processes, on photoreceptors within the
      retina, and on endothelial cells of the posterior ciliary arteries. These results
      may be helpful for understanding the pathophysiological effects of TxA2 in the
      human eye.

PMID- 7819178
TI  - Rhodopsin mutations in a Scottish retinitis pigmentosa population, including a
      novel splice site mutation in intron four.
AB  - Retinitis pigmentosa (RP) is the name given to a group of disorders, both
      clinically and genetically heterogeneous, that primarily affect the photoreceptor
      function of the eye. Mutations in the genes encoding for rhodopsin, RDS
      peripherin, or the beta subunit of the cGMP phosphodiesterase enzyme can be
      responsible for the phenotype. In this study the rhodopsin gene has been screened
      for mutations in a panel of RP individuals and five different sequence changes
      have been detected to date in three dominantly inherited and two unclassified
      families. One of these, a base substitution in the 3'UTR, has not yet been
      confirmed as disease specific, while three missense substitutions have previously
      been reported and are likely to be responsible for the phenotype. The fifth
      change, a base substitution at the intron 4 acceptor splice site, represents a
      novel mutation and is assumed to be the causative mutation.

PMID- 7819180
TI  - Unusual funduscopic manifestations of an ethmoidal mucocele.

PMID- 7819179
TI  - Ocular blood flow measurement.

PMID- 7819181
TI  - Traumatic ocular haemorrhage related to bungee jumping.

PMID- 7819182
TI  - Infectious endophthalmitis after cataract surgery.

PMID- 7819183
TI  - Horner's syndrome and Fuchs' heterochromic uveitis.

PMID- 7819184
TI  - Identification and rapid screening of a DraI RFLP by PCR in the retinoblastoma
      gene.

PMID- 7819185
TI  - Induction of UV-damage recognition protein by cisplatin treatment.
AB  - The biological functions of DNA damage recognition proteins are not well
      understood. Using the band shift assay, we detected in nuclear extracts from
      human carcinoma cell lines damage recognition protein which bound selectively to
      UV-damaged double-stranded DNA. No consistent correlation was found between
      steady-state levels of the UV-damage recognition protein and either cisplatin
      cytotoxicity or DNA repair activity. However, cisplatin treatment caused
      accumulation of the UV-damage recognition protein. The cisplatin-responsive
      induction of UV-damage recognition protein in the nucleus was higher in cisplatin
      resistant cell lines than in their parental counterparts. These results imply
      that the level of inducibility in response to treatment, but not the constitutive
      binding activity, of UV-damage recognition protein correlates with cisplatin
      resistance. Inhibition of UV-damage recognition protein expression by actinomycin
      and cycloheximide suggests that induction of UV-damage recognition protein
      requires de novo RNA and protein synthesis, rather than post-translational
      modification of pre-existing protein. The increased level of UV-damage
      recognition protein after cisplatin treatment could be a direct response to
      adduct formation, since it correlated with the number of Pt-DNA adducts. However,
      it could also be a secondary effect of DNA replication inhibition following DNA
      damage, since inhibition of DNA synthesis by aphidicolin and hydroxyurea caused
      the same induction of UV-damage recognition protein. Inducibility of UV-damage
      recognition protein binding activity by Pt drug treatment suggests involvement of
      this protein in drug resistance, although a direct link between its function and
      DNA repair or damage tolerance has not been demonstrated.

PMID- 7819186
TI  - DNA inhibits the catalytic activity of the alpha subunit of protein kinase CK2.
AB  - The recombinant alpha subunit of protein kinase CK2 (casein kinase 2) from
      Xenopus laevis is inhibited by the addition of single stranded or double stranded
      DNA. This inhibition is competitive with the casein substrate, having an apparent
      Ki of 160 nM for an 86 bp DNA fragment. Assays with a fragment containing the
      putative promoter of the human CK2 beta gene indicated that the affinity of CK2
      for this fragment was not greater than that of other unrelated DNA. The
      inhibitory capacity of DNA toward the protein phosphorylating activity of CK2
      alpha is greatly reduced by the presence of the beta subunit which can completely
      reverse the inhibition. The interaction of CK2 alpha with DNA can also be assayed
      by the nitrocellulose filter binding assay. This assay demonstrates that the
      interaction of CK2 alpha with the tested DNAs is not sequence specific and that
      the beta subunit can also greatly diminish the binding of CK2 alpha to DNA.
      Casein at substrate concentrations also is inhibitory to CK2 alpha DNA binding.
      Likewise, polyanionic inhibitors of the CK2 catalytic activity, such as heparin,
      poly(U), and copoly(Glu:Tyr) polypeptides, can compete for and inhibit the
      binding of DNA to CK2 alpha. However, quercetin, which also inhibits CK2
      phosphorylation activity, and ATP do not affect DNA binding. A mutant CK2 alpha
      in which glutamic acids replace two lysine residues in positions 75 and 76 of the
      alpha peptide chain is less susceptible to DNA inhibition, indicating that this
      basic region of the molecule is involved in its interaction with DNA.

PMID- 7819187
TI  - Properties of a recombinant human uracil-DNA glycosylase from the UNG gene and
      evidence that UNG encodes the major uracil-DNA glycosylase.
AB  - We have expressed a human recombinant uracil-DNA glycosylase (UNG delta 84)
      closely resembling the mature form of the human enzyme (UNG, from the UNG gene)
      in Escherichia coli and purified the protein to apparent homogeneity. This form,
      which lacks the first seven nonconserved amino acids at the amino terminus, has
      properties similar to a 50% homogeneous UDG purified from human placenta except
      for a lower salt optimum and a slightly lower specific activity. The recombinant
      enzyme removed U from ssDNA approximately 3-fold more rapidly than from dsDNA. In
      the presence of 10 mM NaCl, Km values were 0.45 and 1.6 microM with ssDNA and
      dsDNA, respectively, but Km values increased significantly with higher NaCl
      concentrations. The pH optimum for UNG delta 84 was 7.7-8.0; the activation
      energy, 50.6 kJ/mol; and the pI between 10.4 and 10.8. The enzyme displays a
      striking sequence specificity in removal of U from UA base pairs in M13 dsDNA.
      The sequence specificity for removal of U from UG mismatches (simulating the
      situation after deamination of C) was essentially similar to removal from UA
      matches when examined in oligonucleotides. However, removal of U from UG
      mismatches was in general slightly faster, and in some cases significantly
      faster, than removal from UA base pairs. Immunofluorescence studies using
      polyclonal antibodies against UNG delta 84 demonstrated that the major fraction
      of UNG was located in the nucleus. Furthermore, > 98% of the total uracil-DNA
      glycosylase activity from HeLa cell extracts was inhibited by the antibodies,
      indicating that the UNG protein represents the major uracil-DNA glycosylase in
      the cells.

PMID- 7819188
TI  - NMR sequential assignments and solution structure of chlorotoxin, a small
      scorpion toxin that blocks chloride channels.
AB  - The solution structure of chlorotoxin, a small toxin purified from the venom of
      the Leiurus quinquestriatus scorpion, has been determined using 2D 1H NMR
      spectroscopy. Analysis of the NMR data shows that the structure consists of a
      small three-stranded antiparallel beta-sheet packed against an alpha-helix,
      thereby adopting the same fold as charybdotoxin and other members of the short
      scorpion toxin family [Arseniev et al. (1984) FEBS Lett. 165, 57-62; Martins et
      al. (1990) FEBS Lett. 260, 249-253; Bontems et al. (1991) Science 254, 1521
      1523]. Three disulfide bonds of chlorotoxin (Cys5-Cys28, Cys16-Cys33, and Cys20
      Cys35), cross-linking the alpha-helix to the beta-sheet, follow the common
      pattern found in the other short scorpion toxins. The fourth disulfide bridge
      (Cys2-Cys19) links the small N-terminal beta strand to the rest of the molecule,
      in contrast to charybdotoxin where this disulfide bridge is absent and the first
      strand interacts with the rest of the molecule by several contacts between
      hydrophobic residues. Another structural difference between chlorotoxin and
      charybdotoxin is observed at the level of the alpha-beta turn. This difference is
      accompanied by a change in the electrostatic potential surface, which is largely
      positive at the level of this turn in chlorotoxin, whereas no such positive
      potential surface can be found at the same position in charybdotoxin. In the
      latter protein, the positive surface is formed by different charged residues
      situated on the solvent-exposed site of the C-terminal beta-sheet.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7819189
TI  - Inactivation of arginyl-tRNA protein transferase by a bifunctional arsenoxide:
      identification of residues proximal to the arsenoxide site.
AB  - Aminoacyl-tRNA protein transferases catalyze (posttranslational) aminoacylation
      of specific protein N-termini, using aminoacyl-tRNA as substrate. This
      modification targets the protein for ATP-dependent degradation; in eukaryotes,
      degradation occurs in the ubiquitin-mediated pathway. The eukaryotic transferase,
      which catalyzes Arg transfer to N-terminal Glu or Asp residues, is potently
      inhibited by phenylarsenoxides. The gene encoding Arg-tRNA protein transferase
      from the yeast Saccharomyces cerevisiae was subcloned and overexpressed in
      Escherichia coli to provide large amounts of homogeneous protein for a molecular
      analysis of this inhibition. The bifunctional reagent para-[(bromoacetyl)amino]
      phenylarsenoxide is a potent and irreversible inactivator of the yeast
      transferase; the arsenoxide moiety of the reagent directs binding to the enzyme,
      while the alkyl halide moiety alkylates a residue(s) proximal to the arsenoxide
      site. One mole of 14C-labeled reagent was covalently incorporated during
      inactivation, with the side chain of Cys-315 representing the major site of
      alkylation. Mutation of Cys-315 to Ala yielded a fully active enzyme which was
      still subject to stoichiometric, irreversible inactivation by the bifunctional
      arsenoxide. With the C315A-enzyme, the major fraction of the 14C-labeled
      bifunctional reagent was associated with the side chain(s) of one or more of a
      stretch of Glu residues (Glu 339-341). These results show that phenylarsenoxides
      inhibit Arg-tRNA protein transferase by binding to a site that is either itself
      essential, or regulates an essential site. Inhibition appears to occur through a
      steric blockade mechanism.

PMID- 7819190
TI  - Comparison of Pf1 and Fd gene 5 proteins and their single-stranded DNA complexes
      by NMR spectroscopy and differential scanning calorimetry.
AB  - The Pf1 gene 5 protein forms a large helical nucleoprotein complex (Mr = 3.1 x
      10(7)) with single-stranded viral DNA, from which a 32 amino acid sequence rich
      in alanine, proline, and glutamine residues can be removed from the C-terminus by
      limited proteolysis. Sharp resonances in the 1H NMR spectrum of the Pf1
      nucleoprotein complex indicate that the C-terminal region of the protein subunits
      enjoys remarkable conformational flexibility in the complex. In contrast, the
      globular N-terminal domain of the protein subunits is rigidly held and does not
      contribute to the spectrum. The Fd gene 5 protein lacks this C-terminal flexible
      domain, and no distinct resonances can be observed in the 1H NMR spectrum when
      this protein is complexed to single-stranded viral DNA. Differential scanning
      calorimetry shows that the thermal stability of both the Pf1 and Fd gene 5
      protein is increased by 8 degrees C in the complex with DNA, and the transition
      is highly cooperative. Removal of the C-terminal domain of the Pf1 gene 5 protein
      subunits has no appreciable effect either on the Tm of the DNA-protein complex or
      on the cooperative nature of the thermal transition. It is suggested that the C
      terminal domain of the Pf1 gene 5 protein acts as a dynamic clamp which
      kinetically stabilizes the nucleoprotein complex.

PMID- 7819191
TI  - Complete 1H, 13C, and 15N assignments and secondary structure of the GTPase
      activating domain of Gs.
AB  - Complete 1H, 13C, and 15N assignments for backbone and side-chain atoms of the
      145 residue GTPase activating domain of Gs are presented. The combination of
      gradient-enhanced versions of the HNCACB and CBCA(CO)NNH pulse sequences provided
      enough information to obtain sequential backbone assignments for residues 2-145
      of the polypeptide, as well as assignments of asparagine and glutamine side-chain
      amides. HBHA(CO)NNH, HCCH-TOCSY, and 13C/15N NOESY-HSQC experiments yielded side
      chain 1H and 13C assignments. Chemical shift data and 15N NOESY-HSQC experiments
      provided information on the secondary structure of the domain, which is similar
      to that observed in the cognate domain in transducin, a related G protein. The
      functionally essential C-terminal 15 residues are disordered in solution. These
      assignments provide a basis for determining the solution structure of the domain.

PMID- 7819192
TI  - Structural studies of the roles of residues 82 and 85 at the interactive face of
      cytochrome c.
AB  - A combination of structural, functional, and mutagenic experiments has been used
      to study the roles of the invariant Phe82 and highly conserved Leu85 residues in
      cytochrome c, especially with respect to the complexation interface with electron
      transfer partners and maintenance of the hydrophobic heme pocket. Structural
      analyses show that the F82Y, L85A, and F82Y/L85A mutant proteins all retain the
      characteristic cytochrome c fold, but that conformational alterations are
      introduced in the direct vicinity of the mutation sites. In particular, the
      additional hydroxyl group of Tyr82 is in direct spatial conflict with the side
      chain of Leu85 in the F82Y mutant protein, leading to rotation of the side chain
      of Tyr82 out toward the protein surface. This strain is relieved in the F82Y/L85A
      mutant protein where the phenyl ring of Tyr82 is accommodated in a conformation
      comparable to that of the phenylalanine normally present at this location. In
      addition, the available space vacated by the replacement of Leu85 with an alanine
      allows for the inclusion of two new internal water molecules, one of which is
      bound to Tyr82 and the other to Arg13. In contrast, in the L85A mutant protein,
      no internal water molecules are observed in this exclusively hydrophobic pocket,
      which is partially filled by shifts in nearby side chains. Overall, the
      conformational changes observed result from the optimization of side chain
      packing to reflect the spatial requirements of new side chains, the minimization
      of both vacant internal space and the solvent exposure of hydrophobic groups, and
      the attainment of maximal hydrogen bonding between available polar
      groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7819193
TI  - Tertiary stability of native and methionine-80 modified cytochrome c detected by
      proton-deuterium exchange using on-line Fourier transform infrared spectroscopy.
AB  - The stability of the tertiary structure of cytochrome c and of a methionine-80
      chemically modified form of this protein has been investigated by monitoring on
      line the exchange of amide protons with deuterons using infrared spectroscopy.
      The modified protein has a structural stabilization energy of approximately 50%
      of that of native cytochrome c, whereas the secondary structure is not affected
      by the modification. In the modified protein the fraction of slow exchanging
      amides is smaller compared to that in the native protein, and the exchange rate
      constants are found to be 2-3 times larger for the slow (half-life of 5.5 h) and
      intermediate (half-life of 4.1 min) exchanging fraction of amides. The exchange
      rate of a fast exchanging fraction of amides (half-life smaller than 1 min), most
      likely surface exposed amides, is not influenced by tertiary destabilization of
      the protein. The results in aqueous solution agree well with data obtained by
      monitoring the amide-proton exchange using 1H-nuclear magnetic resonance. In
      films, using attenuated total reflection infrared techniques, this difference in
      tertiary stability between modified and native cytochrome c could also be
      demonstrated. The various advantages and complications of this approach are
      discussed in detail.

PMID- 7819194
TI  - Multinuclear magnetic resonance and mutagenesis studies of the histidine residues
      of human mitochondrial ferredoxin.
AB  - Human mitochondrial ferredoxin is a [2Fe-2S] protein that functions to transfer
      electrons from NADPH-dependent ferredoxin reductase to cytochrome P450 enzymes.
      Two of the three histidines of human ferredoxin are strictly conserved in the
      sequences of all known vertebrate ferredoxins, and one of these (His56) is
      adjacent to Cys55, which serves as one of the ligands to the iron-sulfur cluster.
      All but 16 of its residues show sequence identity with those of bovine
      ferredoxin. It has been proposed for bovine ferredoxin that His56 hydrogen bonds
      with a labile sulfur and that the reduction of the iron-sulfur center is
      accompanied by the uptake of a proton by this histidine [Lambeth, J. D., Seybert,
      D. W., Lancaster, J. R., Jr., Salerno, J. C., & Kamin, H. (1982) Mol. Cell.
      Biochem. 45, 13-31]. In this paper, we report procedures for labeling human
      ferredoxin uniformly with 15N using 15NH4Cl and selectively with 13C by the
      incorporation of [U-13C]histidine. Most of the imidazole 1H, 13C, and 15N
      resonances of the three histidines have been assigned by heteronuclear two
      dimensional single- and multiple-bond correlation spectroscopy. Site-directed
      mutagenesis was used in assigning the NMR signals from His56. The pKa values of
      His10 (6.5) and His62 (5.8) in oxidized human ferredoxin were found to be similar
      to those reported previously for the corresponding residues of bovine ferredoxin
      [Greenfield, N. J., Wu, X., & Jordan, F. (1989) Biochim. Biophys. Acta 995, 246
      254; Miura, S., Tamita, S., & Ichikawa, Y. (1991) J. Biol. Chem. 266, 19212
      19216].(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7819195
TI  - Analysis of the hyperfine-shifted nitrogen-15 resonances of the oxidized form of
      Anabaena 7120 heterocyst ferredoxin.
AB  - Hyperfine-shifted nitrogen signals have been detected in one-dimensional 15N NMR
      spectra of oxidized Anabaena 7120 heterocyst ferredoxin labeled uniformly with
      15N. Several of these have been classified by amino acid type by reference to
      results from selective 15N-labeling studies. Remarkable agreement is seen between
      a dipole-dipole analysis of the 15N T1 relaxation and the distances of several of
      the nitrogens from the irons of the cluster as derived from the X-ray structure
      of this protein [Jacobson, B. L., Chae, Y. K., Markley, J. L., Rayment, I., &
      Holden, H. M. (1993) Biochemistry 32, 6788-6793]. The agreement is within
      experimental error for hyperfine-shifted nitrogens that are at least 4.2 A
      distant from either of the irons of the cluster; however, the simple model
      appears to fail for hyperfine-shifted nitrogens that are closer to the cluster.
      The failure of the model for short distances may stem either from a breakdown of
      the point-dipole approximation and/or from neglect of delocalization of unpaired
      electron density from the iron ions to other atoms. Even with the above
      limitations, dipolar analysis of 15N relaxation should provide useful distance
      constraints for solution-state studies of iron-sulfur proteins.

PMID- 7819196
TI  - NMR of Chromatium vinosum ferredoxin: evidence for structural inequivalence and
      impeded electron transfer between the two [4Fe-4S] clusters.
AB  - The 2[4Fe-4S] ferredoxin from Chromatium vinosum has been investigated by 1H and
      13C nuclear magnetic resonance. 1H NMR sequence-specific assignments have been
      obtained for a large majority of the residues. They indicate that the protein
      folds along a pattern similar to that previously evidenced for shorter 2[4Fe-4S]
      ferredoxins. However, C. vinosum ferredoxin differs from other ferredoxins by the
      occurrence of a turn in an eight amino acid region separating two successive
      cysteines, Cys-40 and Cys-49, liganding one cluster. Also, the unique C-terminal
      end of C. vinosum ferredoxin contains a 10 amino acid alpha-helix which interacts
      with one side of the above turn. The only cysteine of the sequence not involved
      in the ligation of the [4Fe-4S] clusters is Cys-57. Specific NMR experiments
      helped characterizing the signals arising from the ligands of these clusters:
      most of them display properties reminiscent of those of homologous ferredoxins,
      except for the signals associated with Cys-40. Despite the general similarity
      between C. vinosum ferredoxin and other 2[4Fe-4S] ferredoxins, the electron
      paramagnetic resonance and NMR spectra of the former reduced protein are
      significantly different from those previously observed for S = 1/2 [4Fe-4S]+
      clusters. In addition, the intramolecular electron transfer rate in C. vinosum is
      far slower than in other similar cases. This is the first report of impeded
      electron exchange between two [4Fe-4S] clusters expected to be less than 12 A
      apart.

PMID- 7819197
TI  - Site-directed isotope labeling and ATR-FTIR difference spectroscopy of
      bacteriorhodopsin: the peptide carbonyl group of Tyr 185 is structurally active
      during the bR-->N transition.
AB  - The largest secondary structural change occurs in the bacteriorhodopsin (bR)
      photocycle during the M-->N transition. In this work site-directed isotope
      labeling (SDIL) and attenuated total reflection Fourier transform infrared (ATR
      FTIR) difference spectroscopy were used to investigate this conformational
      change. L-Tyrosine containing a 13C isotope at the carbonyl carbon was
      selectively incorporated at Tyr 57, Tyr 147, and Tyr 185 by SDIL. This involves
      the cell-free expression of bR in the presence of Escherichia coli suppressor
      tRNA(CUATyr) aminoacylated with L-[1-13C]Tyr. ATR-FTIR difference spectroscopy
      reveals that of the 11 tyrosines, only the peptide carbonyl group of Tyr 185
      undergoes a significant structural change during the bR-->N transition. Along
      with other spectroscopic evidence, this result suggests that the Tyr 185-Pro 186
      region of the protein is structurally active and may function as a hinge which
      facilitates the tilt of the cytoplasmic portion of the F-helix in
      bacteriorhodopsin during the M-->N transition.

PMID- 7819198
TI  - The three-dimensional solution structure of the reduced high-potential iron
      sulfur protein from Chromatium vinosum through NMR.
AB  - The 1H NMR assignment of the reduced HiPIP from Chromatium vinosum available in
      the literature [Gaillard, J., Albrand, J.-P., Moulis, J.-M., & Wemmer, D. E.
      (1992) Biochemistry 31, 5632-5639] has been extended up to 85% of the total
      protein protons. Ninety percent of the nitrogens have been assigned. Then the
      solution structure has been obtained using as many as 1147 meaningful NOE
      connectivities. The protein is sizably paramagnetic even though the ground state
      is a singlet. Nevertheless, the final RMSD values are 0.62 and 1.19 A for the
      backbone and the heavy atoms, respectively. These values compare well with those
      for diamagnetic proteins of the same size. The solution structure is discussed in
      the light of the available structural information from X-ray data.

PMID- 7819199
TI  - Proximity mapping of the Tet repressor-tetracycline-Fe2+ complex by hydrogen
      peroxide mediated protein cleavage.
AB  - We demonstrate in a quantitative in vitro induction assay that tetracycline-Fe2+
      is a more than 1000-fold stronger inducer of Tet repressor compared to
      tetracycline-Mg2+. Oxidative cleavage of the Tet repressor-tetracycline-Fe2+
      complex with H2O2 and ascorbate results in an Fe(2+)-dependent specific
      fragmentation of the protein. The maximal yield of about 15% and a reaction time
      of less than 30 s are only observed in the presence of the drug, whereas about 1%
      cleavage is obtained after 30 min in the presence of Fe2+ without tetracycline.
      Cleavage is not inhibited by several radical scavengers, suggesting a highly
      localized reactivity of the redox-active oxo intermediates in the proximity of
      the Fe(2+)-tc chelater where they are generated. The products can be separated by
      HPLC only after denaturation, indicating that the complex is not disrupted by
      cleavage. Residues at which the cleavage takes place are identified using the
      masses of the fragments determined by electrospray mass spectrometry and their N
      terminal sequences. The major cleavage site maps to residues 104 and 105 of Tet
      repressor. Less efficient cleavages occur at residues 56 and 136, and the least
      efficiently cleaved sites are around residues 144 and 147. The cleavage
      efficiencies correlate to the distances and orientations of the respective
      peptide bonds to Mg2+ in the crystal structure of the Tet repressor-tetracycline
      Mg2+ complex. We discuss potential reaction mechanisms leading to protein
      cleavage.

PMID- 7819200
TI  - Structural and spectroscopic studies of the copper site of stellacyanin.
AB  - The structure of the copper site in oxidized and reduced Rhus vernicifera
      stellacyanin has been studied by X-ray absorption (XAFS) spectroscopy at
      different pH values. Data for the oxidized protein are consistent with the fourth
      ligand being an O- or N-donating ligand rather than a cysteine from the disulfide
      bridge. The fourth ligand is not present in the inner coordination sphere, but
      makes a more distant interaction 2.7 A from the copper atom. Only minor changes
      in the details of the Cu(II) coordination occur when the pH is varied. Direct
      structural information on reduced stellacyanin is provided. Upon reduction, one
      of the histidine ligands moves away from the copper atom by at least 0.2 A. A low
      Z (O or N) scatterer is present approximately 2.4 A from the Cu(I) atom in the
      protein at low pH, and this ligand is lost at high pH. There is no evidence for
      an S-donating fourth ligand in the reduced protein. The XAFS results are
      presented in relation to the spectroscopic and structural information available
      for some methionine-121 mutants of azurin. The data reveal that there are
      spectroscopic similarities between stellacyanin and some of the mutant proteins,
      but distinct structural differences exist that preclude these proteins as
      suitable models for the copper site of stellacyanin.

PMID- 7819201
TI  - Kinase activity of oxygen sensor FixL depends on the spin state of its heme iron.
AB  - FixL is a ferrous heme protein whose kinase activity is inhibited by oxygen. Here
      we show that met-FixL, which is the ferric unliganded form, has the same activity
      as deoxy-FixL, the ferrous unliganded form, indicating that activity does not
      depend on the oxidation state of the heme iron. The ferric derivative fluoro-FixL
      is fully active, indicating that the presence of a heme ligand is not sufficient
      to cause kinase inhibition. An inverse relation between the rate of
      autophosphorylation of ferric FixL and the fractional saturation with cyanide
      shows that the cyanomet form has zero activity. All our active derivatives were
      high-spin, while our inactive derivatives were low-spin. In mixtures of high- and
      low-spin FixL, resulting from partial saturation with low-spin ligands, the
      activity was that which would be expected for the concentration of the high-spin
      component alone. Therefore the spin state of the heme iron rather than the
      oxidation state or presence of ligands must be the factor that controls FixL's
      kinase activity. On transition from low to high spin, the heme iron moves out of
      the porphyrin plane by 0.4 A. We propose that, as in hemoglobin, this motion
      triggers a long-range conformational change which in FixL is responsible for a
      switch to an active form.

PMID- 7819202
TI  - Involvement of glutamate 268 in the active site of human liver mitochondrial
      (class 2) aldehyde dehydrogenase as probed by site-directed mutagenesis.
AB  - On the basis of chemical modification studies, it was postulated that glutamate
      268 was a component of the active site of liver aldehyde dehydrogenase [Abriola,
      D. P., Fields, R., MacKerell, A. D., Jr., & Pietruszko, R. (1987) Biochemistry
      26, 5679-5684]. To study its role, the residue in human liver mitochondrial
      (class 2) aldehyde dehydrogenase was mutated to an aspartate, a glutamine, or a
      lysine, and the enzyme was expressed in Escherichia coli. The mutations did not
      affect the Km values for NAD or propionaldehyde, but grossly affected the
      catalytic activity of the enzymes when compared to recombinantly expressed native
      enzyme; the mutant enzymes had less that 0.4% of the specific activity of the
      recombinantly expressed native aldehyde dehydrogenase. The mutations also caused
      a long lag phase to occur prior to the steady state phase of the reaction. The
      activity of the mutant enzymes could not be restored by the addition of general
      bases such as sodium acetate, sodium formate, or imidazole. The Kd for NADH was
      essentially identical for the E268Q mutant and native enzyme. The three mutant
      forms of the enzyme possessed less than 0.8% of the esterolytic activity of the
      recombinantly expressed native enzyme. Pre-steady state analysis showed that
      there was no burst of NADH formation in the dehydrogenase reaction or of p
      nitrophenol formation in the esterase reaction. This can be interpreted as
      implying that glutamate 268 may function as a general base necessary for the
      initial activation of the essential cysteine residue (302), rather than being
      involved in only the deacylation or hydride transfer step.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7819203
TI  - Characterization of the role of the stimulatory magnesium of Escherichia coli
      porphobilinogen synthase.
AB  - The synthesis of tetrapyrroles is essential to all phyla. Porphobilinogen
      synthase (PBGS) is a zinc metalloenzyme that catalyzes the formation of
      porphobilinogen, the monopyrrole precursor of all biological tetrapyrroles. The
      enzyme from various organisms shows considerable sequence conservation,
      suggesting a common fold, quaternary structure, and catalytic mechanism.
      Escherichia coli and plant PBGS are activated by magnesium, a property that is
      absent from mammalian PBGS. This stimulatory Mg(II) is called Mgc. Mgc is not
      required for activity and is distinct from the two zinc ions (ZnA and ZnB) common
      to mammalian and E. coli PBGS (PBGSE.coli). For PBGSE.coli, both the Km for the
      substrate 5-aminolevulinic acid (ALA) and the Vmax are altered by the presence of
      Mgc; Mg(II) causes the Km to drop from approximately 3 to 0.30 mM and the maximum
      specific activity to increase from 23 to 50 mumol h-1 mg-1. Mgc also causes the
      saturating concentration of the required Zn(II) to decrease from 0.1 mM to 10
      microM. Maximal activation by Mg(II) occurs at 0.5 mM; thus, in E. coli the Mgc
      site is probably saturated under physiological conditions. Mn(II) is a good
      substitute for Mgc, giving a comparable increase in catalytic activity.
      Consequently, Mn(II) has been used as an EPR active probe of the Mgc binding
      site. Mn(II) binds at a stoichiometry of eight ions per enzyme octamer. The X-
      and Q-band EPR spectra reflect a single type of binding site with rhombic
      symmetry and are consistent with oxygen and/or nitrogen ligands. The addition of
      unlabeled or 1-13C-labeled ALA does not significantly affect the Mn(II) EPR
      spectra.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7819204
TI  - Thermal stability and CD analysis of rat tyrosine hydroxylase.
AB  - Tyrosine hydroxylase is the rate-limiting enzyme of catecholamine biosynthesis.
      It is a homotetramer made up of 56 kDa subunits. We examined the thermal
      stability of tyrosine hydroxylase purified from a rat pheochromocytoma cell line
      and investigated the relationship between enzyme activity and stability. Thermal
      stability was assessed by incubating the enzyme at an elevated temperature.
      Unfolding of the protein was followed by measuring the loss of circular dichroism
      (CD) at 220 nm. The CD loss was biphasic, with half-lives of 2 and 14 min at 55
      degrees C in 100 mM potassium phosphate, pH 6.0. The rate of loss of enzyme
      activity paralleled the longer half-life under these conditions. This indicates
      that the structure of the active site is not appreciably change by the unfolding
      events corresponding to the first phase. Moreover, unfolding as assessed by the
      CD spectrum and activity was not reversible and did not exhibit a well-defined
      midpoint temperature or Tm. The thermal stability of the enzyme was altered by
      several factors that influence activity. The enzyme at pH 6.0 was less stable
      (t1/2 = 6.2 and 29 min) than the enzyme at pH 7.2 (a single t1/2 of 64 min).
      Phosphorylated tyrosine hydroxylase had shorter half-lives (t1/2 of 2 and 16 min)
      than the nonphosphorylated enzyme (t1/2 6.2 and 29 min) at pH 6.0, 50 degrees C,
      in 100 mM phosphate. Moderate changes in phosphate concentration had dramatic
      effects on enzyme stability. Decreasing the phosphate concentration from 50 to 10
      mM (pH 6.0) increased the half-life from 2 and 23 min to greater than 120
      min.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7819205
TI  - Azotobacter vinelandii citrate synthase.
AB  - We have purified the citrate synthase from Azotobacter vinelandii and have
      determined that the size of the subunit is 48,000 Da and the structure of the
      holoenzyme is a hexamer. This contrasts with earlier estimates that indicate a
      58,000 Da subunit and a tetrameric structure. In addition, the enzyme is
      allosteric with a Hill coefficient of 1.5 and is inhibited by NADH. The Hill
      coefficient is changed to about 1 by high ionic strength and AMP. The enzyme is
      thus similar to the citrate synthases of many other Gram-negative, facultative,
      anaerobic organisms. In addition, the amino acid sequence of about 100 residues
      has been determined and found to be highly similar to the sequence of Pseudomonas
      aeruginosa citrate synthase.

PMID- 7819207
TI  - Effect of free and ATP-bound magnesium and manganese ions on the ATPase activity
      of chaperonin GroEL14.
AB  - Hydrolysis of ATP by the GroEL14 chaperonin oligomer is activated and modulated
      by Mg2+ or Mn2+ ions. Mg-ATP and Mn-ATP can serve as substrates of the reaction
      and bind in a positively cooperative manner to the same catalytic sites on
      GroEL14, with similar binding constants in the micromolar range. In addition,
      millimolar amounts of Mg2+ and Mn2+ ions can further activate the GroEL14-ATPase
      while interacting with low-affinity noncatalytic sites on the chaperonin. The
      extent of ATPase activation by Mn2+ is half of that by Mg2+ ions. When both Mg2+
      and Mn2+ ions are present in the same reaction, Mn2+ behaves as a noncompetitive
      partial inhibitor of the Mg-dependent ATPase. This inhibition requires the
      presence of ADP in the catalytic site. The binding affinity of Mn-ADP to the site
      is significantly higher than that of Mg-ADP. A slower release of Mn-ADP from the
      catalytic site thus changes the rate-determining step of the GroEL14-ATPase
      cycle. In the cell, the concentrations of Mg2+ and Mn2+ ions are such that both
      divalent ions may modulate chaperonin activity.

PMID- 7819206
TI  - Action of soybean lipoxygenase 1 on 12-iodo-cis-9-octadecenoic acid and 12-bromo
      cis-9-octadecenoic acid.
AB  - The ferric form of soybean lipoxygenase catalyzes an elimination reaction on 12
      iodo-cis-9-octadecenoic acid (12-IODE) to produce iodide ions and 9,11
      octadecadienoic acid (9, 11-ODA). If excess 13(S)-hydroperoxy-cis-9,trans-11
      octadecadienoic acid (13-HPOD) is present, the reaction proceeds until about one
      half of the racemic 12-IODE is consumed; in the absence of excess 13-HPOD, the
      reaction stops after about three turnovers. Ferric lipoxygenase also catalyzes
      the conversion of 12-bromo-cis-9-octadecenoic acid (12-BrODE) to 9,11-ODA at a
      rate that is less than 25% of that observed with 12-IODE. These elimination
      reactions cannot be detected with ferrous lipoxygenase or with lipoxygenase that
      has been inactivated by 5,8,11,14-eicosatetraynoic acid. In the case of 12-IODE,
      elimination is accompanied by a loss of enzymatic activity; at pH 9.0, about 10
      iodide ions are produced per molecule of enzyme inactivated. No inactivation can
      be detected with 12-BrODE. Ascorbate and hydroxylamine, which can act as free
      radical traps, block the inactivation by 12-IODE but do not inhibit the
      elimination reaction. When the enzyme is inactivated by [1-14C]-12-IODE at pH
      9.0, the amount of radioactivity that is covalently bound to the protein is less
      than 30% of that expected for 1:1 incorporation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7819208
TI  - Competitive triplex/quadruplex equilibria involving guanine-rich
      oligonucleotides.
AB  - Oligonucleotide-directed triple helix formation in the purine motif involves the
      binding of guanine-rich oligonucleotides to duplex DNA. Although this approach
      has been proposed for in vivo gene inhibition, triple helix formation by guanine
      rich oligonucleotides is severely inhibited by physiological concentrations of
      certain monovalent cations (M+), especially K+. To clarify the mechanism of this
      inhibition, electrophoretic gel mobility shift titrations were performed to
      analyze the formation and stability of a purine motif triple helix in the
      presence of M+ and to monitor oligonucleotide aggregation under these conditions.
      M+ inhibition of triplex formation exhibited a concentration and ionic radius
      dependence that correlates with the ability of M+ to stabilize guanine quartet
      structures. In the presence of inhibitory [M+], guanine-rich oligonucleotides
      formed aggregates having characteristics consistent with the involvement of
      guanine quartets. The inhibitory effects of K+ on triplex formation could not be
      reversed by addition of the physiological polyamines spermidine3+ or spermine4+.
      M+ reduced the equilibrium concentration of the triplex primarily by decreasing
      the rate of triplex formation, but M+ also caused a detectable increase in the
      rate of triplex dissociation. Together, these results suggest that triplex
      inhibition under physiological ionic conditions is caused by competing equilibria
      wherein guanine-rich oligonucleotides form aggregates involving guanine quartets.
      Approaches to destabilizing aggregates of guanine-rich oligonucleotides under
      physiological conditions will be required before in vivo applications can be
      realistically considered.

PMID- 7819209
TI  - Kinetic studies by fluorescence resonance energy transfer employing a double
      labeled oligonucleotide: hybridization to the oligonucleotide complement and to
      single-stranded DNA.
AB  - A single 16-base oligodeoxyribonucleotide was labeled at the 3'-end with
      fluorescein and at the 5'-end with x-rhodamine (R*oligo*F); the chromophores
      served as a donor/acceptor pair, respectively, for Forster resonance energy
      transfer. We exploited the striking differences in the steady-state emission
      spectra of the R*oligo*F as a single strand and in a duplex structure to signal
      hybridization in solution and to determine the kinetics of duplex formation as
      the probe bound to its oligomer complement and to its target sequence in
      M13mp18(+) phage DNA. The binding followed second-order kinetics; in 0.18 M NaCl
      (pH 8) with 25% formamide, the rate constant for binding to the oligomer
      complement was 5.7 x 10(5) M-1 s-1, and that to M13mp18(+) was 5.7 x 10(4) M-1 s
      1. The source of the 10-fold decrease in the rate of binding to M13mp18(+) was
      examined to differentiate between multiple nonproductive nucleation and rapid
      fluctuations in the structure around the target site. From simulations based on
      each model combined with associated experimental results, we concluded that the
      slower binding was due to rapid structural fluctuations around the target site,
      with an effective target concentration 0.1 of that of the total. Comparisons of
      total fluorescein emission derived from both steady-state and lifetime
      measurements suggest that the 5'-x-rhodamine induces a conformational change that
      affects the interaction at the 3'-end between the fluorescein and the polymer.
      The effects of salt on the fluorescence were complex.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7819210
TI  - Donor-acceptor distance distributions in a double-labeled fluorescent
      oligonucleotide both as a single strand and in duplexes.
AB  - A 16-mer deoxyribonucleotide was labeled at the 5'-end with x-rhodamine and at
      the 3'-end with fluorescein. Forster resonance energy transfer was used to
      determine the distribution, P(R), of donor-acceptor distances for the oligomer in
      three duplex structures (hybridized to complementary strands having 10, 16, and
      24 bases) and as a single strand; measurements were made in 0.18 M NaCl and 1 M
      KCl solutions. These distributions were derived from lifetime measurements made
      in the frequency domain using a multiharmonic frequency phase fluorometer. The
      fluorescein fluorescence decay for each duplex structure was fit very well with
      P(R) modeled as a shifted Gaussian. On the basis of the mean donor-acceptor
      distance, these structures for the 16-mer and the 24-mer were consistent with
      that of B-DNA. For the 16-mer duplex in 0.18 M NaCl, the distribution was
      centered at 68.4 A with sigma = 6.4 A. For the 10-mer duplex, the mean donor
      acceptor distance, 61.8 A, is much larger than that for a structure with the
      fluorophores extended perpendicular to the helix axis. For the single-strand
      data, various high-quality fits yielded physically unreasonable distributions or
      could not accurately account for the acceptor response. Considered analyses
      suggested that the single-strand distribution was best represented by a shifted
      Gaussian, with R = 51.5 A and sigma = 10.0 A in 0.18 M NaCl. In all cases, sigma
      increased and R decreased in 1 M KCl relative to their values in 0.18 M NaCl,
      consistent with the increased flexibility of the polymer.

PMID- 7819211
TI  - Role of H1 in chromatin folding. A thermodynamic study of chromatin
      reconstitution by differential scanning calorimetry.
AB  - In a series of related papers, we have recently presented the results of a
      thermodynamic approach to the conformational transitions of bulk chromatin
      induced in vitro by different structure-perturbing agents, such as the
      intercalating dye ethidium bromide or the ionic strength. In all these studies,
      we took advantage of the capability of differential scanning calorimetry to
      detect the changes in the melting behavior of the structural domains of chromatin
      (the linker and the core particle) associated with the order-disorder
      transitions. This technique also revealed that the higher-order structure
      undergoes a catastrophic decondensation process in the course of the
      transformation of rat hepatocytes as well as of cultured cells. Therefore,
      several questions arose concerning the biological function (if any) of the
      changes in the degree of condensation of bulk chromatin, as well as the mechanism
      of transition and the nature of the modulating agents. In this paper, we report a
      thermodynamic analysis of the reconstitution of H1-depleted calf thymus chromatin
      with the purpose of establishing (1) the binding mode of H1 and (2) the
      energetics and cooperativity of the transition from the unfolded to the condensed
      state. When H1 is progressively extracted from calf thymus nuclei by high-salt
      treatment, the endotherm at 107 degrees C, characteristic of the core particles
      interacting within condensed domains, converts into the thermal transition at 90
      degrees C, resulting from the denaturation of noninteracting core particles.
      Binding of H1 fully restores the thermal profile of native chromatin. Analysis of
      H1 association shows that binding occurs at independent sites with KA = (3.67 +/-
      0.60) x 10(4) M-1 and each site comprising 180 +/- 10 bp. The experimental
      dependence of the fraction of condensed chromatin on R, the moles of bound H1 per
      nucleosome mole, was compared with a simple thermodynamic model for the
      conformational change. This analysis yields a value of -5 kcal per nucleosome
      mole for the interaction free energy of nucleosomes within the ordered state. The
      process of condensation, is not, however, a highly cooperative (all-or-none) one,
      as expected from a consideration of the solenoidal model for the 30 nm fiber.
      Rather, nucleation of the helical state involves the face-to-face interaction
      between consecutive core particles, and the growth is largely determined by the
      mergence and rearrangement of neighboring clusters of helically arrayed
      nucleosomes.

PMID- 7819212
TI  - Thermodynamic and molecular properties of the interaction between amphioxus
      calcium vector protein and its 26 kDa target.
AB  - Calcium vector protein (CaVP) of amphioxus shares some common structural features
      with Ca(2+)-dependent activators such as troponin C and calmodulin, and is
      associated in vivo with a 26 kDa (CaVPT), a multidomain protein with one IQ- and
      two IgII-motifs. Isolated CaVP binds two Ca2+ ions with very different intrinsic
      affinity constants: K'Ca1 = 4.9 x 10(6) M-1 and K'Ca2 = 7.3 x 10(3) M-1,
      respectively. In the complex with CaVPT, CaVP also binds two Ca2+, but with
      strong positive cooperativity (nH = 1.9) and with distinctly higher affinity:
      K'Ca1 = 2.4 x 10(5) M-1 and K'Ca2 = 1.0 x 10(8) M-1. Since neither in the
      isolated CaVP nor in the complex Ca2+ binding is influenced by 2 mM MgCl2, both
      sites can be considered as Ca(2+)-specific. In the absence of Ca2+, the complex
      is stable under physiological conditions, but the interaction is governed by the
      principle of linked functions and Ca2+ binding to CaVP reinforces the affinity
      between CaVP and CaVPT 70-fold. Both proteins interact with the hydrophobic probe
      2 p-toluidinylnaphthalene-6-sulfonate (TNS), but CaVPT enhances the fluorescence
      45-fold, CaVP-Ca2 and metal-free CaVP only 10- and 5-fold, respectively. Complex
      formation between CaVPT and CaVP leads to a 3-fold reduction of the fluorescence
      enhancement, suggesting that a strong solvent-shielded hydrophobic core is
      formed. CaVP contains two highly reactional thiols (kSH > 0.3 s-1) for 5,5'
      dithiobis-(2-nitrobenzoic acid) (DTNB); CaVPT contains three thiols, two of them
      also with kSH > 0.3 s-1 in the native state.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7819213
TI  - Kinetic properties of the alpha 2 beta 1 and alpha 2 beta 2 isozymes of the Na,K
      ATPase.
AB  - The presence of multiple isoforms of the alpha and beta subunits of the Na,K
      ATPase in most mammalian tissues has hindered the understanding of the roles of
      the individual isoforms in directing Na,K-ATPase function. Expression of the Na,K
      ATPase subunits in insect cells using recombinant baculoviruses has proven to be
      a useful system for the study of Na,K-ATPase function. Using this system, we have
      expressed the rat Na,K-ATPase alpha 2 beta 1 and alpha 2 beta 2 isoforms in Sf-9
      insect cells, a cell line derived from the ovary of the fall armyworm, Spodoptera
      frugiperda. Both beta 1 and beta 2 isoforms can efficiently assemble with the
      alpha 2 subunit to produce catalytically competent Na,K-ATPase molecules. The
      analysis of the kinetic properties of both isozymes showed that alpha 2 beta 1
      and alpha 2 beta 2 have equivalent sensitivities to ouabain, and similar turnover
      numbers and apparent affinities for K+ and ATP. The dependence on Na+, however,
      differs between the isozymes, with alpha 2 beta 2 displaying a slightly higher
      apparent affinity for the cation than alpha 2 beta 1. In addition, the even
      greater kinetic differences between Na,K-ATPase isozymes varying in alpha
      isoforms may be important in further differentiating the enzyme. Thus, when
      compared to the rat alpha 1 beta 1 Na,K-ATPase expressed in Sf-9 cells, the alpha
      2 beta 1 and alpha 2 beta 2 isozymes have a lower apparent affinity for K+ and a
      higher affinity for Na+ and ATP.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7819215
TI  - ADP-ribosyltransferase type A from turkey erythrocytes modifies actin at Arg-95
      and Arg-372.
AB  - Turkey erythrocyte ADP-ribosyltransferase A catalyzes the transfer of ADP-ribose
      from NAD to both monomeric and polymeric skeletal muscle alpha-actin with the
      incorporation of 2 mol of ADP-ribose per mol of actin. In contrast, Clostridium
      perfringens iota toxin ADP-ribosylates only G-actin, with modification at
      arginine-177 [Vandekerckhove, J., et al. (1987) FEBS Lett. 255, 48-42].
      Transferase A-catalyzed modifications are sensitive to 0.5 M neutral
      hydroxylamine, consistent with the arginine side chain modification. Radiolabeled
      peptides ADP-ribosylated by transferase A were generated by tryptic digestion and
      purified by reversed phase high-performance liquid chromatography. Amino acid
      sequence and molecular mass analysis identified the ADP-ribosylation sites as Arg
      95 and Arg-372 of actin; both residues are located within subdomain-1 of the
      actin 3D structure [Kabsch, W., et al. (1990) Nature 347, 37-44]. ADP
      ribosylation did not affect cytochalasin D-stimulated G-actin ATPase, the binding
      of actin to DNase I or to gelsolin, or the ability of actin to polymerize.
      Following ADP-ribosylation, however, a prolonged delay in polymerization was
      observed, consistent with a decreased rate of nucleation.

PMID- 7819214
TI  - Human (MDR1) and mouse (mdr1, mdr3) P-glycoproteins can be distinguished by their
      respective drug resistance profiles and sensitivity to modulators.
AB  - Possible functional differences between P-glycoproteins (P-gps) encoded by the
      human MDR1 and mouse mdr1 and mdr3 genes with respect to drug resistance profiles
      and sensitivity to known modulators have been investigated. For this, the three
      genes were introduced and overexpressed in the same cellular background, that of
      Chinese hamster LR73 ovary cells, and drug-resistant clones expressing comparable
      amounts of the corresponding P-gps were selected under the same conditions.
      Analysis of the specific drug resistance profiles encoded by each P-gp for
      colchicine, adriamycin, vinblastine, and actinomycin D revealed overlapping but
      distinct patterns of drug resistance for the three isoforms. While all three P
      gps conferred levels of resistance to vinblastine that did not vary by more than
      2.5-fold, each isoform could be clearly distinguished by its capacity to confer
      resistance to colchicine and actinomycin D. Likewise, the study of structurally
      related and unrelated P-gp modulators indicated strong isoform-specific
      differences in the capacity of individual modulators to abrogate vinblastine
      resistance in the corresponding mdr transfectants. The study of several
      disubstituted piperazine analogs indicated that minor chemical modifications of
      the linker region of this modulator had strong effects on the sensitivity profile
      of each isoform to the modulator. Together, these results indicate that the three
      P-gp isoforms analyzed have specific and distinguishable functional
      characteristics with respect to interactions with drugs and modulators. These
      findings also suggest that P-gp positive murine transplantable tumors should be
      used with caution in the design and in vivo testing of novel P-gp modulators to
      be used to reverse multidrug resistance to tumor cells expressing human MDR1.

PMID- 7819216
TI  - Rho-ADP-ribosylating exoenzyme from Bacillus cereus. Purification,
      characterization, and identification of the NAD-binding site.
AB  - The ADP-ribosyltransferase produced by a pathogenic strain of Bacillus cereus was
      purified to near homogeneity. The transferase is a 28,000 Da molecular mass
      enzyme with a pI of 10.3. The specific enzyme activity is 7.0 nmol of ADP-ribose
      min-1 mg-1 with a Km for NAD of 0.3 microM. Partial amino acid sequence analysis
      of the exoenzyme reveals no significant homology to Clostridium botulinum C3 nor
      to Clostridium limosum exoenzyme. The novel exoenzyme selectively modifies the
      small GTP-binding proteins of the Rho family presumably at the same acceptor
      amino acid (Asn-41) as determined for C3. Besides cellular Rho, recombinant RhoA
      and -B are substrates for the exoenzyme. However, recombinant Rac1 and CDC42,
      although belonging to the Rho family, are not modified. B. cereus exoenzyme was
      photolabeled with [carbonyl-14C]NAD resulting in inhibition of ADP
      ribosyltransferase and NAD-glycohydrolase activity. A glutamic acid residue was
      identified as part of the NAD-binding site which corresponds to Glu-174 of C3.
      This glutamic acid is located in a domain which shows high homology with the C
      terminal part of C3 exoenzyme, C. limosum exoenzyme, and Staphylococcus aureus
      EDIN and which probably represents the catalytic site of the transferases. The
      data indicate that B. cereus exoenzyme is a novel member of the family of C3-like
      ADP-ribosyltransferases which share the same substrate protein Rho and which have
      an identical highly conserved catalytic domain.

PMID- 7819217
TI  - Observation of a secondary tritium isotope effect in the chorismate synthase
      reaction.
AB  - Chorismate synthase, the seventh enzyme on the shikimate pathway, catalyzes the
      formation of chorismate from 5-enolpyruvylshikimate 3-phosphate (EPSP). This
      reaction involves the loss of phosphate from C(3) and hydrogen from the C(6) pro
      R position of EPSP. In order to probe the mechanism of this reaction, [3-(3)H,
      14C]EPSP has been synthesized and a secondary V/K tritium kinetic isotope
      measured for the reaction catalyzed by Neurospora crassa chorismate synthase. A
      small but significant value of kH/kT = 1.047 +/- 0.012 was observed. The reaction
      is also shown to be effectively irreversible. Previous experiments have measured
      a primary deuterium isotope effect on V/K at C(6) [Balasubramanian, S., Abell,
      C., & Coggins, J. R. (1990) J. Am. Chem. Soc. 112, 8581-8583], and there is
      additionally evidence in support of a flavin intermediate in the mechanism
      [Ramjee, M. N., Coggins, J. R., Hawkes, T. R., Lowe, D. J., & Thorneley, R. N. F.
      (1991) J. Am. Chem. Soc. 113, 8566-8567]. In the light of these observations the
      reaction mechanism probably involves cleavage of the C(6)-H and C(3)-O bonds in
      distinct but partially rate determining steps.

PMID- 7819218
TI  - Fluorescent nucleotide derivatives as specific probes for the uncoupling protein:
      thermodynamics and kinetics of binding and the control by pH.
AB  - Fluorescent 2'-O-dansylated (DANS) purine nucleotides were synthesized. The
      fluorescence of the nucleotide derivatives is quenched in aqueous solutions but
      strongly enhanced on binding to the uncoupling protein (UCP) from brown adipose
      tissue mitochondria. The fluorescence enhancement was 30-, 10-, and 10-fold for
      DANSGTP, DANSATP, and DANSADP. One mole of DANS nucleotide binds to 1 mol of
      dimeric UCP. The binding affinity ranges from 10(5) to 10(8) M-1, similar to that
      of the unsubstituted nucleotides, while dansylation of AMP increases the affinity
      50-fold. The pH dependence in the pKD/pH plots for the DANS nucleotides is
      basically similar to that for the unsubstituted nucleotides, i.e., for nucleoside
      diphosphates the slope delta pKD/delta pH < -1 at pH 5-6.5, = -1 at pH > 6.8, and
      only for triphosphates = -2 at pH > 7.2. Two different protonation sites with a
      pKH approximately 4 (Asp/Glu) and pKH approximately 7.2 (His), only for
      nucleoside triphosphates, are suggested to be involved in binding. The higher
      affinity of DANSGTP indicates additional participation in binding of the C-6
      oxygen on the guanine. The binding as measured with the anion exchange method
      agrees with the fluorescence measurement for DANSGTP, whereas for the more
      loosely binding DANSATP it is 40% lower. This is interpreted in terms of
      tight/loose UCP-nucleotide complexes, 100% tight complex for DANSGTP (as well GTP
      or ATP) but 40% loose complex for DANSATP. By measuring the rapid kinetics using
      the fluorescence signal, the binding rate is found to be fast and fairly constant
      for the various nucleotides, whereas the dissociation is slow and strongly
      nucleotide dependent. The rates are pH dependent with delta pkon/delta pH = 1 for
      all the nucleotides and delta pkoff/delta pH = -1 for DANSNTP but more weakly
      with delta pkoff/delta pH < -0.5 for DANSADP and DAN-ATP. The pH dependence of
      the binding rate corresponds to a protonation at the carboxylate group (Glu/Asp).
      The high pH dependence of the dissociation rate only for DANSNTP is explained by
      deprotonation at the HisH+ which is involved only in nucleoside triphosphate
      binding. This is in line with the very strong pH dependence of nucleoside
      triphosphate affinity above pH 7 with a delta pKD/delta pH = -2 as an important
      regulatory mechanism for the H+ transport activity of UCP. The differences of the
      DANS nucleotides versus the DAN and unsubstituted nucleotides as well as the
      nucleoside tri- versus diphosphate are rationalized in a specific H+ dependent
      regulatory mechanism at the binding site.

PMID- 7819219
TI  - Water requirements in monomer folding and dimerization of triosephosphate
      isomerase in reverse micelles. Intrinsic fluorescence of conformers related to
      reactivation.
AB  - The possibility of using reverse micelles to stabilize monomers prior to
      formation of dimeric triosephosphate isomerase (TPI) from rabbit muscle was
      studied. TPI denatured with guanidine hydrochloride undergoes reactivation in
      reverse micelles formed with n-octane, hexanol, cetyltrimethylammonium bromide,
      and water. Reactivation of around 80% is observed at TPI concentrations of about
      2 micrograms/mL of reverse micelles and water concentrations above 4.0%. With
      3.0% water, reactivation is about 10%. If denatured TPI is incubated for a few
      seconds in reverse micelles with 5.0% water (or higher) followed by incubation in
      3.0% water, reactivation is between 35% and 50%. That is, a brief exposure of
      denatured TPI to reverse micelles with a relatively high water concentration
      yielded a significant amount of structures competent for formation of
      catalytically active dimers. As evidenced by kinetic data, these structures
      correspond to monomers of TPI [Garza-Ramos, G. Tuena de Gomez-Puyou, M., Gomez
      Puyou, A., & Gracy R. W. (1992) Eur. J. Biochem. 208, 389-395]. After a 5-2.0%
      water transition, competent monomers were stabilized for at least 30 min; a
      subsequent rise in water concentration led to dimerization and appearance of
      activity. By changes in the amount of water, it was possible to determine in
      reverse micelles the amount of water required for monomer folding and
      dimerization; i.e., less water was required in the dimerization step. Experiments
      with a model system, trypsin and the soybean inhibitor, showed that, in reverse
      micelles with 2.0% water, protein-protein interactions readily take
      place.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7819220
TI  - Transcriptional activity of a fluorinated vitamin D analog on VDR-RXR-mediated
      gene expression.
AB  - The transcriptional activity of the hexafluorinated derivative of 1,25
      dihydroxyvitamin D3 [1,25-(OH)2D3], 26,26,26,27,27,27-hexafluoro-1,25
      dihydroxyvitamin D3 [F6-1,25-(OH)2D3], was examined in cultured cells by a
      transient expression assay (CAT assay) using expression vectors for the rat
      nuclear vitamin D3 receptor (VDR) and the rat 9-cis-retinoic acid receptor (RXR
      beta), and a reporter plasmid containing a consensus vitamin D3 response element
      (VDRE) consisting of two directly repeated AGGTCA motifs spaced by 3 bp (DR3). At
      physiological concentrations, the transcriptional activity of F6-1,25-(OH)2D3 was
      2-4 times more potent than that of 1,25-(OH)2D3 in both nontarget (HeLa) and
      target (UMR106) cells for 1,25-(OH)2D3. The transcriptional activity of F6-1,25
      (OH)2D3 was also higher when the endogenous target gene (osteopontin), which has
      a VDRE related to the DR3 in its promoter, was induced. A gel-shift assay using
      DR3 as a probe and in vitro synthesized receptors showed that the ligand-induced
      DNA binding of VDR required RXR to form a heterodimer. Moreover, in this assay we
      found that F6-1,25-(OH)2D3 induced the receptor-DNA complex at a 10-fold lower
      concentration than 1,25-(OH)2D3 without influencing the dissociation kinetics.
      However, the binding affinity of F6-1,25-(OH)2D3 for VDR was slightly lower than
      that of 1,25-(OH)2D3. The increased DNA binding of ligand-bound VDR by
      introducing hexafluorines into 1,25-(OH)2D3 may potentiate the transcriptional
      activity. Thus, the higher biological activity of F6-1,25-(OH)2D3 may be exerted
      at least in part by enhanced transcriptional activity.

PMID- 7819221
TI  - Mutational analysis of the catalytic residues lysine 230 and tyrosine 160 in the
      NADP(+)-dependent isocitrate dehydrogenase from Escherichia coli.
AB  - Two site-directed mutants of isocitrate dehydrogenase (IDH) of Escherichia coli
      have been studied by site-directed mutagenesis kinetic and structural studies.
      Substitution of phenylalanine for tyrosine at position 160 (Y160F) showed 0.4% of
      the kcat of wild-type with isocitrate as substrate, while the Km for isocitrate
      remained unchanged. When the postulated intermediate, oxalosuccinate, was
      enzymatically decarboxylated, Y160F showed a higher kcat and a similar Km to the
      wild type values. The rate of reduction of oxalosuccinate to isocitrate by the
      Y160F mutant was greatly decreased relative to the wild-type. Substitution of
      methionine for lysine at position 230 decreased kcat to 1.1% of that of the wild
      type and Km increased by a factor of 500-600. The decarboxylation of
      oxalosuccinate was undetectable for the K230M mutant. The structure of the site
      directed mutants of IDH with and without a bound complex of isocitrate and Mg2+
      was solved at 2.5 A resolution and compared by difference mapping against
      previously determined enzyme structures. The structural studies show that (i) the
      overall protein-folding side chain conformations and active sites of both mutants
      are isomorphous with wild-type enzyme, (ii) isocitrate and magnesium bind to both
      enzyme mutants with the same relative conformation and binding interactions as
      wild-type enzyme, and (iii) the mutated side chains (Phe 160 and Met 230) are
      positioned for catalysis in a similar conformation as that observed for the wild
      type enzyme. Hence, the alteration of the side chain functional groups is
      directly related to the loss of enzyme activity. Possible roles of the active
      site tyrosine and lysine are discussed.

PMID- 7819222
TI  - Structural basis for the sequence-specific DNA strand cleavage by the enediyne
      neocarzinostatin chromophore. Structure of the post-activated chromophore-DNA
      complex.
AB  - Neocarzinostatin chromophore (NCS chrom) belongs to a family of highly potent
      enediyne antitumor antibiotics which bind to specific DNA sequences and cause
      single- and/or double-strand lesions. NCS chrom-DNA complexes have eluded
      structural studies since the native form of the drug is extremely labile in
      aqueous conditions. We report the three-dimensional structure of the stable
      glutathione post-activated NCS chrom (NCSi-glu)-DNA complex [NCSi-glu
      d(GGAGCGC).d(GCGCTCC)] using NMR and distance geometry-molecular dynamics
      simulation methods. NCSi-glu interacts with the GCTC tetranucleotide on one
      strand and with the AGC trinucleotide on the other strand through the unique
      intercalation at the 5'-CT/5'-AG step and minor groove binding. The DNA-drug
      complex exhibits an extended, unwound V-shaped intercalation site and wider and
      shallower grooves than the free DNA duplex. The structure of the complex
      manifests specific van der Waals interactions and H-bond formation between the
      carbohydrate moiety and a specific DNA sugar/phosphate. Prominent among those are
      the contacts of the NCSi-glu residues with the functional groups in the minor
      groove that are characteristic of individual DNA bases. These results provide a
      structural model for understanding the sequence specificity of the single- and
      double-strand cleavage at the AGC and related sites by the enediyne NCS chrom.

PMID- 7819223
TI  - Structure of a duplex oligodeoxynucleotide containing propanodeoxyguanosine
      opposite a two-base deletion in the (CpG)3 frame shift hotspot of Salmonella
      typhimurium hisD3052 determined by 1H NMR and restrained molecular dynamics.
AB  - Structural refinement from solution 1H NMR data was performed on the 5'
      d[ATCGC(PdG)-CGGCATG]-3'.5'-d[CATGCCGCGAT]-3' duplex, in which the adducted
      oligodeoxynucleotide containing the exocyclic lesion 1,N2-propano-2'
      deoxyguanosine (PdG) was annealed with the complementary strand which contained a
      CpG deletion. The resulting duplex required PdG and one adjacent cytosine to be
      unpaired. A total of 352 distances were utilized to restrain molecular dynamics
      calculations, of which 264 were NOE-derived. These distances were calculated
      using complete relaxation matrix methods from hybrid matrices, which were
      comprised of the experimentally determined distances and additional distances
      derived from either A-form or B-form DNA. A simulated annealing protocol combined
      with the distance restraints was able to refine a single structure with an
      average rms deviation of < 1.35 A. The accuracy of the refined structure was
      assessed using full relaxation matrix calculations, which gave good agreement
      with measured NOE intensities. PdG was found to be stacked into the helix below
      base pair C3.G18, whereas C5 was found to be unpaired and extruded toward the
      major groove and parallel to base pair G6.C17. This created a localized bend in
      the DNA helix of approximately 20-35 degrees at the junction between PdG and C5.
      The bending corroborated previous assays performed on this modified sequence
      [Moe, J. G., Reddy, G. R., Marnett, L. J., & Stone, M. P. (1994) Chem. Res.
      Toxicol. 7, 319-328].

PMID- 7819224
TI  - Recognition and cleavage of single-stranded DNA containing hairpin structures by
      oligonucleotides forming both Watson-Crick and Hoogsteen hydrogen bonds.
AB  - A new approach is described to design antisense oligonucleotides targeted against
      single-stranded nucleic acids containing hairpin structures by use of both Watson
      Crick and Hoogsteen hydrogen bond interactions for recognition. The
      oligonucleotide has two different domains, one allowing double helix formation
      involving Watson-Crick base pairs and the other one forming a triple helix
      involving Hoogsteen-type base triplets in the major groove of a hairpin stem.
      Spectroscopic and gel retardation experiments provided evidence for such Watson
      Crick/Hoogsteen (WC/H) recognition of hairpin structures in single-stranded DNA.
      An antisense oligonucleotide designed to form only Watson-Crick base pairs was
      unable to disrupt the stable stem structure of the target under conditions where
      the oligonucleotide designed with the Watson-Crick/Hoogsteen interactions could
      bind efficiently to the hairpin-containing target. The addition of one nucleotide
      to the oligonucleotide at the junction between the double helix and triple helix
      regions in WC/H complexes had an effect on stability which was dependent on the
      relative orientation of the Watson-Crick and Hoogsteen domains in the target. An
      oligodeoxynucleotide-phenanthroline conjugate targeted against such a hairpin
      containing DNA fragment induced specific cleavage in the double-stranded stem.
      This WC/H approach may be useful in designing artificial regulators of gene
      expression.

PMID- 7819225
TI  - Site-specificity of the second-site suppressor mutation of the Asp-285-->Asn
      mutant of metal-tetracycline/H+ antiporter of Escherichia coli and the effects of
      amino acid substitutions at the first and second sites.
AB  - The deleterious effect of the mutation of Asp-285 to Asn of the metal
      tetracycline/H+ antiporter (TetA) of Escherichia coli is suppressed by the second
      site mutation of Ala-220 to an acidic amino acid residue (Yamaguchi, A.,
      O'yauchi, R., Someya, Y., & Sawai, T. (1993) J. Biol. Chem. 268, 26990-26995). In
      this study, site-specific second-site Glu mutants as to 11 different positions
      around position 220 were established from the Asp-285-->Asn mutant TetA protein.
      Among them, only the Ala-220-->Glu mutant completely suppressed the deleterious
      effect of the Asp-285-->Asn mutation, indicating that position 220 is highly
      specific for the suppression. Although E. coli cells producing second-site Glu
      mutants as to positions 213, 216, 217, 218, 219, 221, 222, and 223 of the Asn-285
      mutant were as tetracycline sensitive as the host cells without TetA, Gly-224-
      >Glu and Pro-227-->Glu second-site mutants of the Asn-285 mutant conferred low
      level tetracycline resistance, the levels decreasing in this order. These two
      positions and position 220 are on the same side of putative transmembrane helix
      VII. The Phe-289-->Asp mutation, which is located at a position one-alpha-helical
      turn downstream from Asp-285 in the same putative helix, IX, did not suppress the
      Asn-285 mutation. The introduction of an acidic residue at the second site was
      essential for suppression of the Asn-285 mutation because Lys-220 and Gln-220
      second-site mutants of the Asn-285 mutant showed very low tetracycline
      resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7819226
TI  - DNA damage-induced transcriptional activation of a human DNA polymerase beta
      chimeric promoter: recruitment of preinitiation complex in vitro by ATF/CREB.
AB  - Treatment of hamster cells in culture with the DNA alkylating agent N-methyl-N'
      nitro-N-nitrosoguanidine (MNNG) induces DNA polymerase beta (beta-pol) gene
      expression and cellular levels of the enzyme. Transcriptional activity of a
      cloned beta-pol promoter in transient expression assays is also stimulated. Among
      the requirements for these responses are methylation damage to genomic DNA,
      cellular cAMP-dependent protein kinase, and the ATF/CREB site of the cloned beta
      pol promoter. In the present study, HeLa cell nuclear extract from MNNG-treated
      cells was much more active in an in vitro transcription assay than nuclear
      extract from normal cells. By using an oligonucleotide affinity column to deplete
      the nuclear extract of ATF/CREB, we showed that the difference was due to
      ATF/CREB activator. Purified ATF/CREB activator from MNNG-treated cells was
      approximately 10-fold more active than ATF/CREB purified from normal cells as a
      transcriptional activator for the depleted nuclear extract. ATF/CREB in the
      extract from normal cells is known to activate in vitro transcription by
      increasing the rate of promoter clearance [Narayan, S., Widen, S. G., Beard, W.
      A., & Wilson, S. H. (1994) J. Biol. Chem. 269, 12755-12763]. With ATF/CREB from
      MNNG-treated cells, the amount of preinitiation complex formed was much greater
      than with ATF/CREB from normal cells, and the kinetics of both the closed to open
      preinitiation complex isomerization and promoter clearance were altered. These
      results indicate that the mechanism of transcriptional activation secondary to
      DNA alkylation damage is recruitment of more preinitiation complex and alteration
      of the kinetic scheme of transcription initiation.

PMID- 7819227
TI  - Role of quinone-mediated generation of hydroxyl radicals in the induction of
      glutathione S-transferase gene expression.
AB  - Induction of glutathione S-transferase (GST) Ya gene expression by a variety of
      chemical agents is mediated by a regulatory element composed of two adjacent AP-1
      like binding sites and activated by the Fos/Jun heterodimeric complex (AP-1). We
      have previously shown that the induction of GST Ya gene expression and of AP-1
      binding activity is regulated by intracellular glutathione (GSH) levels. To study
      the role of reactive oxygen species in the induction of AP-1 activity and GST Ya
      gene expression and their effect on intracellular GSH levels, we have exposed
      hepatoma cells to adriamycin and two synthetic quinones, Qcb and Qn, with
      different capacities to generate oxygen radicals. The kinetics of quinone
      mediated generation of hydroxyl radicals were monitored in intact cells by a spin
      trapping technique and EPR spectral measurements. We find that quinones which can
      chelate Fe(III) ions, adriamycin and Qcb, are more effective in hydroxyl radical
      production than the nonchelating quinone Qn. Furthermore, we show that the
      induction of AP-1 binding activity and GST Ya gene expression by these quinones
      correlates with their oxygen radical production, adriamycin and Qcb being
      stronger inducers that Qn. The present study indicates that the AP-1-mediated
      induction of GST Ya gene expression is part of the response to oxidative stress.
      A transient increase by 2.5-fold in the intracellular GSH level was observed 30
      min after exposure of cells to quinone and was followed by a rapid depletion of
      GSH. This increase in the GSH level represents an induction of GSH synthesis
      since it was blocked by buthionine sulfoximine, an inhibitor of gamma
      glutamylcysteine synthetase.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7819228
TI  - Generation and elimination of 8-oxo-7,8-dihydro-2'-deoxyguanosine 5'
      triphosphate, a mutagenic substrate for DNA synthesis, in human cells.
AB  - 8-Oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate (8-oxo-dGTP) is a potent
      mutagenic substrate for DNA synthesis. The present study deals with generation
      and degradation of 8-oxo-dGTP in the nucleotide pool of human cells. (1) 8-Oxo
      dGTP can be generated not only by direct oxidation of dGTP but also by
      phosphorylation of 8-oxo-dGDP by nucleoside diphosphate kinase. (2) 8-Oxo-dGTP is
      rapidly degraded to 8-oxo-dGMP by cellular 8-oxo-dGTPase activity. 8-Oxo-dGMP
      thus produced cannot be rephosphorylated; guanylate kinase, which phosphorylates
      both GMP and dGMP to the corresponding nucleoside diphosphates, is totally
      inactive for 8-oxo-dGMP. (3) 8-Oxo-dGMP is further degraded to 8-oxo
      deoxyguanosine by a nucleotidase. The enzyme was partially purified from an
      extract of human Jurkat cells, and the mode of action was elucidated. 8-Oxo-dGMP
      is the most preferred substrate of the enzyme, and other nucleoside
      monophosphates are cleaved at significantly lower rates: Km for 8-oxo-dGMP is 10
      times lower than that for dGMP, the second best substrate for the enzyme. The
      enzyme appears to convert 8-oxo-dGMP, which accumulates in the cellular
      nucleotide pool, to a form readily excretable to the cell exterior.

PMID- 7819229
TI  - Mutagenic specificity of reductively activated 1-nitropyrene in Escherichia coli.
AB  - 1-Nitropyrene (1-NP), the predominant nitropolycyclic hydrocarbon found in diesel
      exhaust, is a mutagen and tumorigen. Nitroreduction is a major pathway by which 1
      NP is metabolized. In order to study the distribution of DNA adducts and the
      mutational specificity of reductively activated 1-NP, single stranded M13mp18 DNA
      was treated with N-hydroxyl-1-aminopyrene generated in situ to give > 95% of one
      major adduct, N-(deoxyguanosin-8-yl)-1-aminopyrene. A primer was annealed to DNA
      containing different levels of adducts, and polymerase extension on these
      templates was studied. Replication inhibition, primarily at or 3' to guanine
      bases, was observed. Transfection of these M13 DNA in Escherichia coli indicated
      a dose-dependent reduction in viability with concomitant enhancement in
      mutagenesis in the lacZ gene fragment. Approximately two adducts per genome
      constituted one lethal hit (approximately 37% viability). Both survival and
      mutagenesis were increased when SOS functions of the host cell were induced. N
      (Deoxyguanosin-8-yl)-1-aminopyrene mutagenesis appeared to be SOS-dependent. With
      SOS induction, one-base deletions and insertions were the major event (45%),
      although base substitutions also occurred at high frequency (44%). A major
      proportion of the point mutations, and particularly one-base deletions and
      insertions, were detected in 5'-CG, 5'-GC, or 5'-GG sequences. Analysis of the
      mutation data suggested that N-(deoxyguanosin-8-yl)-1-aminopyrene-induced
      mutations occurred predominantly at the adduct site, but mutations at the base
      located next to it have been detected at a significant frequency as well. A large
      fraction of point mutations occurred in a hairpin loop region.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7819230
TI  - Isolation and in vitro phosphorylation of sensory transduction components
      controlling anaerobic induction of light harvesting and reaction center gene
      expression in Rhodobacter capsulatus.
AB  - Anaerobic induction of light harvesting and reaction center gene expression
      involves two transacting factors termed RegA and RegB. Sequence and mutational
      analysis has indicated that RegA and RegB constitute cognate components of a
      prokaryotic sensory transduction cascade with RegB comprising a membrane-spanning
      sensor kinase and RegA a cytosolic response regulator. In this study we have
      purified RegA, as well as a truncated portion of RegB (RegB') and undertaken an
      in vitro analysis of autophosphorylation and phosphotransfer activities.
      Incubation of RegB' with [gamma-32P]ATP and MgCl2 resulted in phosphorylation of
      RegB' (RegB' approximately P) over a 20-min incubation period. Incubation of
      RegB' approximately P with RegA resulted in rapid transfer of the phosphate from
      RegB' to RegA. In analogy to other characterized prokaryotic sensory transduction
      components, mutational and chemical stability studies also indicate that RegB' is
      autophosphorylated at a conserved histidine and that RegA accepts the phosphate
      from RegB at a conserved aspartate.

PMID- 7819231
TI  - Evidence for residual structures in an unfolded form of yeast phosphoglycerate
      kinase.
AB  - The unfolding-refolding transition of phosphoglycerate kinase followed by steady
      state fluorescence has clearly shown the existence of a hyperfluorescent form
      [Missiakas et al. (1990) Biochemistry 29, 8683-8689]. In order to determine the
      contribution of each of the two tryptophans to the fluorescence properties of the
      enzyme in the equilibrium transition and to characterize the hyperfluorescent
      form, two single tryptophan mutants in which tryptophans 308 and 333 were
      replaced by a tyrosine and a phenylalanine, respectively, were constructed.
      Neither the catalytic nor the physicochemical properties of the enzyme are
      significantly altered by these mutations. The unfolding-refolding transitions
      were studied using circular dichroism and tryptophan fluorescence emission. Both
      tryptophans contribute to the hyperfluorescence observed in the first transition.
      For guanidine hydrochloride concentrations higher than 0.9 M, it clearly appears
      that the second transition results from a further unfolding. It is accompanied by
      a decrease in fluorescence intensity and a 5 mm red shift of the maximum emission
      wavelength. When the unfolding is induced by urea, the end of the transition
      corresponds to the hyperfluorescent state. Further addition of guanidine
      hydrochloride induces complete unfolding. These results suggest the presence of
      residual microstructures around tryptophan 308 and tryptophan 333 in the
      hyperfluorescent state. The characterization of these clusters and their
      contribution as starting structures in the folding process are now under
      investigation.

PMID- 7819232
TI  - Structural basis for the catalytic activity of aspartate aminotransferase K258H
      lacking the pyridoxal 5'-phosphate-binding lysine residue.
AB  - Chicken mitochondrial and Escherichia coli aspartate aminotransferases K258H, in
      which the active site lysine residue has been exchanged for a histidine residue,
      retain partial catalytic competence [Ziak et al. (1993) Eur. J. Biochem. 211, 475
      484]. Mutant PLP and PMP holoenzymes and the complexes of the latter (E. coli
      enzyme) with sulfate and 2-oxoglutarate, as well as complexes of the
      mitochondrial apoenzyme with N-(5'-phosphopyridoxyl)-L-aspartate or N-(5'
      phosphopyridoxyl)-L-glutamate, were crystallized and analyzed by means of X-ray
      crystallography in order to examine how the side chain of histidine 258 can
      substitute as a general acid/base catalyst of the aldimine-ketimine
      tautomerization in enzymic transamination. The structures have been solved and
      refined at resolutions between 2.1 and 2.8 A. Both the closed and the open
      conformations, identical to those of the wild-type enzyme, were observed,
      indicating that the mutant enzymes of both species exhibit the same
      conformational flexibility as the wild-type enzymes, although in AspAT K258H the
      equilibrium is somewhat shifted toward the open conformation. The replacement of
      the active site K258 by a histidine residue resulted only in local structural
      adaptations necessary to accommodate the imidazole ring. The catalytic competence
      of the mutant enzyme, which in the forward half-reaction is 0.1% of that of the
      wild-type enzyme, suggests that the imidazole group is involved in the aldimine
      ketimine tautomerization. However, the imidazole ring of H258 is too far away
      from C alpha and C4' of the coenzyme-substrate adduct for direct proton transfer,
      suggesting that the 1,3-prototropic shift is mediated by a water molecule.
      Although there is enough space for a water molecule in this area, it has not been
      detected. Dynamic fluctuations of the protein matrix might transiently open a
      channel, giving a water molecule fleeting access to the active site.

PMID- 7819233
TI  - DNA-nogalamycin interactions: the crystal structure of d(TGATCA) complexed with
      nogalamycin.
AB  - The structure of the self-complementary deoxyoligonucleotide d5'(TGATCA)
      complexed with nogalamycin, an antitumor anthracycline, has been solved to 1.8 A
      resolution using X-ray crystallographic methods. The technique of single
      isomorphous replacement, utilizing the anomalous signal of bromine in derivative
      data collected at three different wavelengths, Cu K alpha, Mo K alpha, and 0.91 A
      synchroton radiation, was used. The complex crystallized in space group
      P4(1)2(1)2 with unit cell dimensions a = 37.2 A and c = 70.1 A. The final
      structure including 116 water molecules has an overall R factor of 19.5% for the
      4767 reflections with F > or = 1 sigma F in the resolution range 10.0-1.8 A. One
      nogalamycin molecule intercalates between each of the d5'(TpG) steps at both ends
      of a distorted B DNA double helix. This structure provides the first three
      dimensional picture of nogalamycin bound to the triplet sequence d5'(TGA), one of
      its favorable natural binding sites. The drug exhibits a strict requirement for
      binding to the 3' side of a pyrimidine and the 5' side of a purine. Nogalamycin
      has bulky sugar groups at either end of a planar aglycon chromophore; therefore,
      in order for intercalation to occur, the DNA must either transiently open or flex
      along the helix axis to allow insertion of the chromophore between the base
      pairs. Conformational change in nogalamycin is observed in the drug-DNA complex
      with respect to free nogalamycin. Nogalamycin binding to DNA induces severe
      deformation to the intercalation site base pairs. In comparison to previously
      reported anthracycline-DNA structures significant differences in base-pair
      geometry, drug hydrogen-bonding patterns, and the extent of hydration are
      observed. The position of the drug in this complex is stabilized by a number of
      nonbonded forces including van der Waals interactions and extensive direct and
      solvent-mediated hydrogen bonds to the DNA duplex.

PMID- 7819234
TI  - Enzymatic and nonenzymatic polarizations of alpha,beta-unsaturated ketosteroids
      and phenolic steroids. Implications for the roles of hydrogen bonding in the
      catalytic mechanism of delta 5-3-ketosteroid isomerase.
AB  - Ketosteroids (e.g., 19-nortestosterone) and phenolic steroids (e.g., 17 beta
      estradiol and 17 beta-dihydroequilenin), which are potent competitive inhibitors
      of delta 5-3-ketosteroid isomerase (isomerase, EC 5.3.3.1) of Pseudomonas
      testosteroni, undergo significant polarization upon binding to the active site of
      the enzyme. The 10 nm red shift of the UV absorption maximum of the enone
      chromophore of 19-nortestosterone, which occurs in the enzyme-steroid complex,
      resembles that observed when this steroid is exposed to strong acid. The UV and
      fluorescence spectral changes of 17 beta-estradiol and 17 beta-dihydroequilenin
      in the enzyme-bound complex resemble the spectra of ionized phenolate species in
      aqueous basic solutions. Since most enzymes bind their substrates and competitive
      inhibitors in a solvent-inaccessible hydrophobic environment, and the generation
      of charges in such nonpolar environments is unfavorable, we investigated the
      possibility that the spectral perturbations of the steroids might arise from
      strong hydrogen bonding in nonpolar environments. For this purpose, the spectral
      properties of model compounds capable of forming intramolecular hydrogen bonds
      were studied in nonpolar solvents. Thus, 4-hydroxyandrost-4-ene-3,17-dione, in
      which the 4-hydroxyl group is intramolecularly hydrogen-bonded to the 3-carbonyl
      group through a five-membered ring, exhibits a lambda max of 276.0 nm, while the
      corresponding 4-methyl ether, 4-methoxyandrost-4-ene-3,17-dione, which cannot
      form an internal hydrogen bond, shows a lambda max of 258.5 nm in aqueous
      solution.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7819235
TI  - Analysis of the kinetic and redox properties of NADH peroxidase C42S and C42A
      mutants lacking the cysteine-sulfenic acid redox center.
AB  - The flavoprotein NADH peroxidase from Enterococcus faecalis 10C1 has been shown
      to contain, in addition to FAD, an unusual cysteine-sulfenic acid (Cys-SOH) redox
      center. The non-flavin center cycles between reduced (Cys-SH) and oxidized (Cys
      SOH) states, and the 2.16 A crystal structure of the non-native cysteine-sulfonic
      acid (Cys-SO3H) form of the wild-type peroxidase supports the proposed catalytic
      role of Cys42. In this study, we have employed a site-directed mutagenesis
      approach in which Cys42 is replaced with Ser and Ala, neither side chain of which
      is capable of redox activity. Reductive titrations of both C42S and C42A mutants
      lead directly to full FAD reduction with 1 equiv of either dithionite or NADH,
      consistent with elimination of the Cys-SOH center. Direct determinations of the
      redox potentials for the FAD/FADH2 couples yield values of -219 and -197 mV,
      respectively, for C42S and C42A peroxidases, indicating that the presence of
      Cys42-SH in the two-electron-reduced wild-type enzyme lowers the flavin potential
      by approximately 100 mV. Anaerobic stopped-flow analyses of the reduction of C42S
      and C42A peroxidases by NADH demonstrate that in both cases flavin reduction is
      rapid; these results are confirmed by enzyme-monitored, steady-state kinetic
      analyses which, in addition, give turnover numbers approximately 0.04% that of
      wild-type enzyme. These results are entirely consistent with the role proposed
      for Cys42 in the catalytic redox cycle of wild-type NADH peroxidase and
      indirectly support its function as a peroxidatic center in the homologous NADH
      oxidase.

PMID- 7819236
TI  - Isomerization of trans-2,delta 5-dienoyl-CoA's to delta 3,delta 5-dienoyl-CoA's
      in the beta-oxidation of delta 5-unsaturated fatty acids.
AB  - The NADPH-dependent reduction pathway for the metabolism of delta 5-unsaturated
      fatty acids involves the isomerization of trans-2,delta 5-dienoyl-CoA, initially
      formed from the dehydrogenation of delta 5-enoyl-CoA, to isomeric delta 3,delta 5
      dienoyl-CoA. The latter intermediates were then isomerized to trans-2,trans-4
      dienoyl-CoA, which then follows the NADPH-dependent pathway mediated by 2,4
      dienoyl-CoA reductase. The isomerization from trans-2,delta 5-dienoyl-CoA to
      delta 3,delta 5-dienoyl-CoA is catalyzed by delta 3,delta 2-enoyl-CoA isomerase.
      In this investigation, we identified the stereoisomers of delta 3,delta 5
      dienoates that were formed in the reaction. Starting from trans-2,cis-5
      decadienoyl-CoA, the isomerization produced cis-3,cis-5- and trans-3,cis-5
      decadienoates. On the other hand, trans-2,trans-5-decadienoyl-CoA yielded cis
      3,trans-5- and trans-3,trans-5-decadienoates. In addition to purified rat liver
      delta 3,delta 2-enoyl-CoA isomerase, acyl-CoA oxidase from Arthrobacter also
      catalyzed the isomerization from trans-2,cis-5-dienoyl-CoA. However, this acyl
      CoA oxidase could not catalyze the similar isomerization of trans-2,trans-5
      dienoyl-CoA. delta 3,delta 5-t-2,t-4-Dienoyl-CoA isomerase used cis-3,cis-5-,
      trans-3,cis-5-, and cis-3,trans-5-dienoyl-CoA's as substrates and converted them
      to trans-2,trans-4-dienoyl-CoA. In contrast, trans-3,trans-5-dienoyl-CoA was not
      a substrate for this isomerization. Extensive purification of acyl-CoA oxidase
      through column chromatography could not remove or diminish the isomerization
      activity associated with acyl-CoA oxidase. Acyl-CoA oxidases derived from Candida
      and rat liver also possess isomerization activity.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7819237
TI  - Oligosaccharide behavior of complex natural glycosphingolipids in multicomponent
      model membranes.
AB  - Wideline 2H NMR of model membranes was used to consider the molecular
      consequences of factors often suggested as modulators of complex
      glycosphingolipid oligosaccharide arrangement and motional characteristics at
      cell surfaces. GM1, asialo-GM1, and globoside were studied as examples of plasma
      membrane recognition sites. The experimental approach involved substitution of
      deuterons (D) for protons at specific locations within the carbohydrate chains.
      Deuterated glycolipids were then dispersed at 7-10 mol% in unsonicated bilayers
      of 1-palmitoyl-2-oleoylphosphatidylcholine. Factors tested for their significance
      to carbohydrate chain conformation and dynamics included glycolipid natural alkyl
      and acyl chain variability, membrane fluidity, and the presence of cholesterol
      and a charged sugar residue (neuraminic acid). Effects of Ca2+ and membrane
      associated protein were briefly considered. Two distinct strategies were employed
      in substituting deuterons for selected protons of carbohydrate residues. Neither
      approach necessitated alteration of the glycolipid natural fatty acid
      composition. (i) Protons of the exocyclic hydroxymethyl group on the terminal Gal
      residue of GM1 and asialo-GM1, and on the terminal N-acetylgalactosamine (GalNAc)
      residue of globoside, were replaced with deuterium (producing -CDHOH) by an
      enzymatic oxidation/reduction cycle. This represents the first application of
      such an approach to deuteration of complex neutral glycolipids. Spectral results
      were compared to those obtained for the similarly-deuterated monoglycosyl lipid,
      galactosylceramide (GalCer), with natural fatty acid composition. Efficacy of
      this labeling method may in principle be influenced by structural variations
      within a given glycolipid family. Also, asymmetric rotation of the deuterated
      group made it less attractive than the second method for relating spectral
      features to receptor geometry. (ii) A general synthetic, nonenzymatic method was
      investigated for replacing amino sugar N-acetyl groups with deuterated acetate (
      COCD3). The acetate group of the GalNAc residue of globoside, GM1, and asialo
      GM1, as well as that on neuraminic acid in GM1, was replaced with -COCD3. This
      second method afforded better signal-to-noise--an important consideration for 2H
      NMR. The NMR technique employed had the potential for detecting changes of as
      little as 10% in oligosaccharide orientation or motional order. Each glycolipid
      demonstrated clear evidence of preferred average oligosaccharide conformations in
      all (fluid) membrane environments examined. The most striking observation was
      that, in fluid matrices, conformation and motional order of the complex
      oligosaccharide chains were only modestly influenced by factors tested, including
      natural variation in the glycolipid hydrocarbon chains, membrane fluidity,
      temperature, and the presence of cholesterol or the N-acetylneuraminic acid
      (NeuAc) residue on GM1.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7819238
TI  - Modification of the electrostatic environment is tolerated in the oxyanion hole
      of the cysteine protease papain.
AB  - The oxyanion hole in cysteine and serine proteases can be viewed as an
      arrangement of prealigned dipoles that complements the changes in charge
      distribution during the enzymatic reaction. Because of the electrostatic nature
      of the interaction involved in the oxyanion hole, the introduction of charged
      residues in that region could have a major effect on the catalytic properties of
      the enzyme. In this study, residue Gln19, which contributes to one of the
      hydrogen bonds in the oxyanion hole of papain, has been replaced by glutamic
      acid, histidine, and asparagine residues. These mutations result in 65-315-fold
      decreases in kcat/KM, supporting our previous finding that the side chain of
      Gln19 contributes to transition state stabilization in the oxyanion hole of
      papain (Menard et al., 1991a). Since papain is active over a wide range of pH
      values, the influence of side chain ionization on activity could be measured
      quantitatively with the mutant Gln19Glu. The pH dependency of kcat/KM for
      Gln19Glu is not of the classical bell-shaped form normally observed for papain,
      but instead is modulated by ionization of the Glu19 side chain with a pKa of
      6.02. The Gln19Glu mutant at low pH, where the Glu19 side chain is neutral, is
      the enzyme that displays activity closest to that of wild-type enzyme, with a
      (kcat/KM)1lim value only 20-fold lower than that for papain. As expected, the
      activity of the Gln19Glu mutant decreases when the Glu19 side chain ionizes.
      However, introduction of the negatively charged glutamate into the oxyanion hole
      of papain leads to a further reduction in activity of only 12-fold, and this
      mutant is still more active than the Gln19Ser enzyme and only 3-fold less active
      than Gln19Asn.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7819239
TI  - Stability studies on maize leaf phosphoenolpyruvate carboxylase: the effect of
      salts.
AB  - The solution stability of phosphoenolpyruvate carboxylase (PEPC) has been
      determined in the presence of various salts by temperature-accelerated enzyme
      inactivation and also by using high-performance size-exclusion chromatography.
      Kosmotropic (water structuring) anions in the Hofmeister series (HPO(4)2-,
      citrate3-, SO(4)2-, F-, OAc-) and glutamate stabilized the enzyme most
      effectively, while Cl- (a borderline Hofmeister anion) and Br- (a chaotropic
      anion) were destabilizing. The effects of the cations on PEPC stability ranged
      from relatively inert (Na+, K+) to destabilizing ((CH3)4N+, NH4+, Li+). The
      observed stabilization of PEPC by specific salts has been interpreted in terms of
      the positive surface tension increment and the water-structuring effects
      conferred on the solution by the specific stabilizing reagents. Both these
      effects enhance hydrophobic interactions of proteins and increase the energy
      required to enlarge the surface area of the solvent cavity in which the protein
      resides. The destabilization of PEPC by some salts at a concentration of 0.5 M
      was associated with the dissociation of the tetrameric enzyme into its dimeric
      and monomeric forms, a process most probably occurring as a result of ion-peptide
      dipole binding, which promotes protein-solvent interaction and a subsequent
      reduction in the free energy of cavity formation. The stabilization of enzyme
      activity by kosmotropic salts depended on the salt concentration with maximum
      stabilization of PEPC in solution at 52 degrees C observed with 0.6-0.8 M sodium
      glutamate, 2 M KF, and 2.2 M KOAc. Higher concentrations of these salts resulted
      in decreased activity. This reduction in activity of PEPC in the presence of high
      concentrations of kosmotropic salts appears to be associated with irreversible
      conformational changes of the tetrameric enzyme.

PMID- 7819240
TI  - Localization of the factor IX propeptide binding site on recombinant vitamin K
      dependent carboxylase using benzoylphenylalanine photoaffinity peptide
      inactivators.
AB  - The propeptide binding/activation site on the vitamin K dependent carboxylase has
      been localized to a region of carboxylase between residues Arg +50 and Glu +225
      by photoinactivation studies using [125I]tyrosyl-labeled benzoylphenylalanine
      (Bpa)-containing analogs of proFIX19, a peptide containing residues -18 to +1 of
      factor IX. Four proFIX19 analogs with Bpa substituents at -16, -13, -7, and -6
      were synthesized. These peptides were specific photoinactivators of carboxylase
      and were used to label a His6-carboxylase construct produced in baculovirus
      infected insect cells. Fragments of the labeled carboxylase produced by V8
      protease digestion were analyzed by peptide-specific antibodies and by
      autoradiography. The propeptide recognition site was localized to the N-terminal
      one-third of the 94 kDa carboxylase. This is consistent with previous studies
      using a carboxylase substrate affinity label, N-(bromoacetyl)-FLEELY [Kuliopulos,
      A., Nelson, N.P., Yamada, M., Walsh, C.T., Furie, B., Furie, B.C., & Roth, D.A.
      (1994) J. Biol. Chem. 269, 21364-21370], indicating that the propeptide binding
      site and the FLEEL binding site are both located within the N-terminal one-third
      of the vitamin K dependent carboxylase.

PMID- 7819241
TI  - Allosteric regulation of the ATP sulfurylase associated GTPase.
AB  - ATP sulfurylase catalyzes and chemically links the hydrolysis of GTP and the
      synthesis of activated sulfate (APS). Like many GTPases, its GTPase activity is
      allosterically regulated, in this case, by APS-forming reactants and their
      analogues. Using these activators, we have been able to mimic many of the
      complexes that form in the native reaction, including an E.AMP intermediate. The
      effects of each of these complexes on GTP hydrolysis are determined. The results
      of pre-steady-state and isotope trapping studies demonstrate that the binding of
      activator and substrate to the enzyme are near equilibrium and that the rate
      determining step appears to be scission of the beta, gamma-bond of GTP. These
      properties of the system allow the energetic consequences of activator binding on
      the ground- and transition-state complexes to be evaluated. Activation occurs
      predominantly by transition-state stabilization, resulting in kcat increases. The
      values for kcat span a 180-fold range and vary with each activator. Km, or ground
      state, effects are relatively small, approximately 3-fold, and are uniform
      throughout the activator series. These studies provide an in-depth view of the
      energetic interactions between the two active sites at each step of the APS
      forming reaction.

PMID- 7819242
TI  - Intramolecular electron transfer and conformational changes in cytochrome c
      oxidase.
AB  - The photolysis intermediates of partially and fully reduced CO-bound cytochrome
      oxidase derivatives were investigated. A gated optical spectrometric multichannel
      analyzer was used to collect visible and near-infrared transient difference
      spectra on time scales from nanoseconds to milliseconds. The spectra were
      analyzed by a singular value decomposition method combined with a global
      exponential fitting procedure. Global analysis of the mixed-valence CO complex
      transient difference spectra shows that five intermediates are present with
      apparent lifetimes of 1.4 microseconds, 4.8 microseconds, 76.7 microseconds, 10.6
      ms, and 21.6 ms. The data were fitted to a kinetic model involving a sequential
      pathway with accompanying equilibria. On the basis of this mechanism, the
      absorption spectra of the intermediates were determined. The first step, also
      present in the fully reduced enzyme, is attributed to a conformational change at
      cytochrome a3. The spectral changes associated with the second step are similar
      to those expected for 1:1 electron transfer from cytochrome a3 to cytochrome a,
      except for a higher absorbance between 480 and 550 nm. A comparison of the
      experimental spectral change associated with this step, (a2+ minus a3+) minus
      (a3(2+) minus a3(3+), and the calculated spectral change, (a2+ CuA+ minus a3+
      CuA2+) minus a3(2+) CuB+ minus a3(3+) CuB2+), allowed extraction of the
      absorbance spectrum of CuA2+ in the 480-550 nm region. The spectral change
      associated with the third step is consistent with the oxidation of cytochrome a.
      A decrease in the 830 nm band on the same time scale indicates that the electron
      acceptor is CuA. The data also suggest that the redox state of CuB significantly
      affects the absorption spectrum of oxidized cytochrome a3 in the visible region.
      The two processes on a millisecond time scale are attributed to CO recombination
      and intramolecular electron transfer.

PMID- 7819244
TI  - Structure and properties of the bacteriochlorophyll binding site in peripheral
      light-harvesting complexes of purple bacteria.
AB  - In this paper, we have examined, using FT resonance Raman spectroscopy, the
      bacteriochlorophyll (BChl) binding sites in the peripheral light-harvesting
      complexes extracted from a number of purple bacterial strains. A comparison of
      interactions of the BChl molecules with their binding sites in these LH2
      complexes, together with the primary sequences of the alpha and beta
      polypeptides, allows three amino acids to be proposed to be involved in the
      hydrogen bonding of the 9-keto carbonyl of one of the 850-nm-absorbing pair of
      BChl molecules. Specifically, we show that one keto carbonyl group, which is
      strongly hydrogen bonded in Rhodobacter sphaeroides LH2, is involved in much
      weaker interactions in the LH2 complexes from all the other species studied
      (i.e., Rhodobacter capsulatus, Rubrivivax gelatinosus, Rhodopseudomonas
      palustris, Rhodopseudomonas acidophila, and Rhodopseudomonas cryptolactis). This
      is correlated with the presence of three polar amino acids in the primary
      sequence of the alpha polypeptide of Rb. sphaeroides which are absent in the
      sequences from all the other bacteria and probably close to a chromophore. These
      three residues are a serine at position -4, a threonine at position +6 and
      another serine at position +17 (numbering relative to the conserved histidine,
      considered as position 0), in the alpha polypeptide of Rb. sphaeroides.
      Furthermore, the study of the interactions in natural B800-820 complexes shows
      that the two 2-acetyl groups of the 820-nm-absorbing BChl molecules are free from
      hydrogen-bonding interactions. In the light of previous site-selected mutagenesis
      studies, the lack of such hydrogen bonds seems to be a general phenomenon,
      associated with the 820-nm absorption of LH2 complexes, and suggests that
      hydrogen-bonding interactions have a precise molecular role in finely tuning the
      functional properties of these complexes.

PMID- 7819243
TI  - Interaction of alpha-crystallin with spin-labeled peptides.
AB  - alpha-Crystallin is a major protein of the vertebrate lens once thought to be
      highly specialized for conferring transparency. However, recent work has revealed
      a wide tissue distribution and a sequence homology to small heat shock proteins,
      suggesting a more general role for the protein. Like other molecular chaperons,
      alpha-crystallin is known to bind to unfolded proteins and suppress nonspecific
      aggregation in vitro. In the present work, spin-labeled derivatives of the
      insulin B chain and melittin were used to investigate the state of these proteins
      bound to alpha-crystallin. Insulin was selected since unfolding can be triggered
      by reduction of the interchain disulfide bonds, a treatment that does not affect
      alpha-crystallin. Upon reduction of insulin, the separated B chains aggregate. In
      the presence of alpha-crystallin, the B chains bind to alpha-crystallin and
      aggregation is suppressed. Melittin, a 26 amino acid peptide from bee venom, was
      selected for study since it is a random coil under physiological conditions, and
      its interaction with alpha-crystallin can be directly studied. EPR analysis of
      the spin-labeled peptides shows that the nitroxide side chains are immobilized in
      a polar environment on alpha-crystallin and that they are separated by 25 A or
      more in the complex, indicating that the bound proteins are not clustered. The
      bound B chains of insulin are not in a fully extended conformation, and melittin
      does not appear to bind to a hydrophobic surface in alpha-crystallin as an
      amphipathic helix, as it does to membranes and some other proteins.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7819245
TI  - On the mechanism of inhibition of the neutrophil respiratory burst oxidase by a
      peptide from the C-terminus of the large subunit of cytochrome b558.
AB  - A peptide (RGVHFIF) from near the carboxyl terminus (residues 559-565) of gp91
      phox, the large subunit of cytochrome b558, was previously shown to inhibit
      activation of the respiratory burst oxidase [Kleinberg, M. E., Malech, H. L., &
      Rotrosen, D. (1990) J. Biol. Chem. 265, 15577-15583]. The peptide has been
      proposed to compete with gp91-phox binding to p47-phox, one of the cytosolic
      oxidase components. In the present studies, we have used a semirecombinant system
      consisting of recombinant cytosolic factors (p47-phox, p67-phox, and Rac1) along
      with isolated plasma membrane to investigate the mechanism by which the peptide
      inhibits oxidase activation. In an in vitro translocation model, the peptide
      inhibited arachidonate-activated translocation of both p47-phox and p67-phox to
      the plasma membrane. The kinetic mechanism of inhibition was examined. Inhibition
      was noncompetitive or mixed with respect to not only Rac and p67-phox but also to
      p47-phox. We suggest that the peptide, rather than competing for cytochrome-p47
      phox interactions, inhibits indirectly, perhaps by binding to and altering the
      conformation of cytochrome b558.

PMID- 7819246
TI  - Heat-stable inhibitor protein derived peptide substrate analogs: phosphorylation
      by cAMP-dependent and cGMP-dependent protein kinases.
AB  - The phosphorylation of substrate peptides derived from PKI, the heat-stable
      inhibitor protein of the cAMP-dependent protein kinase (PKA), has been studied
      with both PKA and the cGMP-dependent protein kinase (PKG) using a variety of
      substitution and deletion analogs. On the basis of Km, kcat and kcat/Km values,
      (Ser21)PKI alpha(14-22) amide (numbering based upon native PKI alpha) is the most
      effective peptide substrate yet discovered for either kinase, although other
      peptides, while phosphorylated considerably less efficiently by PKG, are more
      specific. Although the inhibitory peptide corresponding to this sequence (i.e.,
      with an Ala at position 21) is a much more potent inhibitor of PKA than of PKG
      (approximately 250-fold), PKG actually exhibits a 60% higher kcat than does PKA
      with the (Ser21)PKI alpha(14-22) amide substrate peptide, with only a 20-fold
      higher Km value. The two key PKI residues within this peptide which were found to
      be essential for substrate activity with both kinases were Arg18 (P-3) and Ile22
      (P+1). The Arg19 (P-2) residue, which contributes significantly to both PKI-based
      peptide inhibitors and substrates of PKA, was only a more minor contributor to
      PKG substrate efficacy. Of particular note, the Phe10 (P-11) residue, which
      contributes very substantially to high affinity binding of both PKI and longer
      PKI peptide inhibitors, neither positively nor negatively affects the kinetics of
      either PKA or PKG with PKI-based substrates.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7819247
TI  - Barbiturates inhibit hexose transport in cultured mammalian cells and human
      erythrocytes and interact directly with purified GLUT-1.
AB  - Barbiturates reduce cerebral blood flow, metabolism, and Glc transfer across the
      blood-brain barrier. The effect of barbiturates on hexose transport in cultured
      mammalian cell lines and human erythrocytes was studied. Pentobarbital inhibits
      [3H]-2-dGlc uptake in 3T3-C2 murine fibroblasts by approximately 95% and
      approximately 50% at 10 and 0.5 mM, respectively. Uptake of [3H]-2-dGlc is linear
      with time in the presence or absence of pentobarbital, and the percent inhibition
      is constant. This suggests that hexose transport, not phosphorylation, is
      inhibited by barbiturates. Inhibition by pentobarbital of hexose transport in 3T3
      C2 cells is rapid (< 1 min), is not readily reversible, is not altered by the
      presence of albumin [1% (w/v)], and is independent of temperature (4-37 degrees
      C) and the level of cell surface GLUT-1. The IC50's for inhibition of hexose
      transport in 3T3-C2 cells by pentobarbital, thiobutabarbital, and barbital are
      0.8, 1.0, and 4 mM, respectively. This is consistent with both the Meyer-Overton
      rule and the pharmacology of barbiturates. Neither halothane (< or = 10 mM) nor
      ethanol [< or = 0.4% (v/v)] significantly inhibits hexose transport. Inhibition
      by pentobarbital (0.5 mM) of [3H]-2-dGlc uptake by 3T3-C2 cells decreases the
      apparent Vmax (approximately 50%) but does not alter the apparent Km
      (approximately 0.5 mM). Inhibition of hexose transport by barbiturates, but not
      ethanol [< or = 0.4% (v/v)], is also observed in human erythrocytes and four
      other cultured mammalian cell lines. Pentobarbital quenches (Qmax approximately
      75%) the intrinsic fluorescence of purified and reconstituted GLUT-1 (Kd
      approximately 3 mM). Quenching is independent of Glc occupancy, is unchanged by
      mild proteolytic inactivation, and does not appear to directly involve
      perturbations of the lipid bilayer. We propose that barbiturates can interact
      directly with GLUT-1 and inhibit the intrinsic activity of the carrier. Glc
      crosses the blood-brain barrier primarily via the GLUT-1 of the endothelial cells
      of cerebral capillaries. Partial inhibition of this process by barbiturates may
      be of significance to cerebral protection.

PMID- 7819248
TI  - Human apolipoprotein E mediates processive buoyant lipoprotein formation in
      insect larvae.
AB  - The expression of human apolipoprotein E in tobacco hornworm larvae causes a
      dramatic change in the buoyant density of the insect's endogenous lipoproteins.
      Larvae without apoE have lipoproteins that are found exclusively in the high
      density range. Baculovirus-mediated apoE expression results in the conversion of
      approximately one-fourth of the endogenous lipoproteins to low-density species.
      This density conversion is progressive and parallels a similar change in apoE
      density distribution. ApoE is secreted from the lipoprotein producing fat body
      tissue in a lipid-poor form, but readily associates with circulating insect
      lipoproteins in the hemolymph where the density conversion takes place. Analysis
      of the buoyant lipoprotein particles indicates that they contain apoE and insect
      apolipophorins I and II with few or no other proteins present.
      Immunoprecipitation of apolipophorins I and II results in coprecipitation of
      apoE. This association is disrupted by detergent, consistent with the three
      proteins sharing the same lipoprotein particles. The ability of apoE to influence
      buoyant lipoprotein formation in an invertebrate system leads us to suggest that
      small apolipoproteins such as apoE may play a role in buoyant lipoprotein
      production in mammals.

PMID- 7819249
TI  - Dissecting titin into its structural motifs: identification of an alpha-helix
      motif near the titin N-terminus.
AB  - Titin, also known as connectin, is a giant modular protein specifically found in
      vertebrate striated muscle. Since the huge size of titin does not allow a direct
      structure determination, we have started a long-term project to characterize the
      protein by cutting it into smaller domains or structural units. The major part of
      the titin sequence is assembled by modules approximately 100 amino acids long
      that belong to two major protein superfamilies. Most of these modules are linked
      together by stretches of variable length with unique sequence. No direct
      structural characterization has been achieved so far for any of these linkers. We
      present here a study of a stretch located in the titin N-terminus and part of a
      linker between two modules. Our attention was drawn toward this region because it
      shows 100% probability to form a coiled coil when analyzed by a prediction
      program. A synthetic 38 amino acid peptide spanning such a sequence was studied
      in aqueous solution by circular dichroism, nuclear magnetic resonance, and
      analytical ultracentrifugation at various pH, salt, and peptide concentrations.
      Under all conditions, it shows a strong tendency to form alpha-helical
      structures. In the presence of salt, this conformation is associated with the
      formation of helical bundles below pH 5. Above pH 5, any aggregate breaks, and
      the titin peptide is a monomeric helix in equilibrium with its random coil
      conformation. We discuss the factors which stabilize the helical conformation and
      the possible role of this stretch in vivo.

PMID- 7819250
TI  - Molecular mobility of the Ca(2+)-deficient EF-hand of cardiac troponin C as
      revealed by fluorescence polarization of genetically inserted tryptophan.
AB  - To probe attitudinal features of the Ca(2+)-deficient site (site I) in the Ca2+
      switch of cardiac troponin C (cTnC), we have examined steady-state fluorescence
      emission and polarization of a Trp26 inserted in a recombinant cardiac TnC
      (cTnC3.W) and compared these with the properties of the Ca(2+)-competent site I
      in skeletal TnC (sTnC4.W). The Ca(2+)-induced fluorescence emission in cTnC3.W
      was a fraction (25-30%) of that in sTnC4.W, in agreement with previous
      observations on the Ca(2+)-deficient site incorporated in a cardiac/skeletal
      chimera c1/s.W [Gulati, J. & Rao, V. G. (1994) Biochemistry 33, 9052-9056]. Thus,
      the fractional quantum yield reflected intrinsic properties of the cardiac metal
      ion-deficient site I. Conversely, in sTnC-1.W, where the skeletal site I also was
      made Ca(2+)-deficient by D27-->A substitution, the Ca(2+)-induced quantum yield
      was lower than that in cTnC3.W. Nevertheless, similar steady-state fluorescence
      polarizations for Ca(2+)-saturated sTnC4.W and cTnC3.W indicated
      indistinguishable final conformations in the two activated TnC isoforms. In EGTA,
      the polarization parameter (PEGTA) of sTnC4.W is greater than that of cardiac
      TnC, and the cardiac PEGTA value is closer to the activated PCa. Comparison of
      the chimera c1/s.W with sTnC-1.W indicated that the differences in conformation
      of the site I Trp for the EGTA-treated cardiac/skeletal isoforms were due to the
      structural disparities in this region. This contention was further supported by
      examination of the chimera CBc1/s.W, where the cardiac EF-hand was altered by
      27VLGA30-->DAD substitution. Polarization of the relaxed form was similar to that
      for sTnC4.W. These findings suggest that the relaxed conformation of the cardiac
      Ca2+ switch is more favorably predisposed to activation than the skeletal switch.

PMID- 7819251
TI  - Polyanion-induced alpha-helical structure of a synthetic 23-residue peptide
      representing the lysine-rich segment of the N-terminal extension of yeast
      cytoplasmic aspartyl-tRNA synthetase.
AB  - Conformational studies were performed on the synthetic tricosapeptide N-acetyl
      SKKALKKLQKEQEKQRKKEERAL-amide, representing the highly basic segment (residues 30
      52) of the N-terminal extension of yeast cytoplasmic aspartyl-tRNA synthetase.
      Circular dichroism experiments show that, in aqueous solution at neutral pH, the
      peptide adopts a random conformation. The effects of pH, temperature, addition of
      trifluoroethanol (TFE), and titration with polyanions on the conformation of the
      peptide were studied. In TFE or in the presence of an equimolar concentration of
      (phosphate)18, the peptide adopts a 100% alpha-helical conformation. A partially
      alpha-helical conformation is induced by (phosphate)4 or d(pT)8 (respectively 40%
      and 35% helical content). Raising the pH in aqueous solution promotes 75% alpha
      helicity, with a transition pK of 9.9 reflecting deprotonation of lysine
      residues. On the basis of these results, nuclear magnetic resonance studies were
      carried out in TFE as well as in aqueous solution in the presence of
      (phosphate)18, to determine the structure of the molecule. Complete 1H resonance
      assignments were obtained by conventional two-dimensional NMR techniques. A total
      of 138 interproton constraints derived from NOESY experiments were used to
      calculate the three-dimensional structure by a two-stage distance
      geometry/simulated annealing procedure. The two deduced structures were highly
      similar and show that nine cationic residues are segregated on one face of a
      helical structure, providing an ideal polycationic interface for binding to
      polyanionic surfaces.

PMID- 7819252
TI  - Interaction of tryptophan-182 with the retinal 9-methyl group in the L
      intermediate of bacteriorhodopsin.
AB  - An intense indole N-H stretching vibrational band at 3486 cm-1 in the difference
      Fourier transform infrared spectrum is one of the characteristic features of the
      L intermediate of bacteriorhodopsin [Maeda, Sasaki, Ohkita, Simpson, & Herzfeld
      (1992) Biochemistry 31, 12543]. This band is now assigned to tryptophan-182. The
      Trp182-->Phe (W182F) protein shows specific features in the difference spectrum
      in the visible region upon L formation, and exhibits great delay in the L-M
      conversion. Fourier transform infrared difference spectra further indicate that
      while the intensity of the C-methyl in-plane bending vibration at 1009 cm-1 is
      lost in the L intermediate of the wild type, its intensity remains high in the
      W182F protein. The intensity of the N-H stretching vibration upon L formation is
      diminished considerably in an artificial bacteriorhodopsin containing 9
      desmethylretinal. It also exhibits delayed M formation. These results suggest
      that Trp182 interacts with the retinal side chain through the 9-methyl group, and
      thereby affects the L-to-M conversion.

PMID- 7819253
TI  - Effects of the enediyne C-1027 on intracellular DNA targets.
AB  - We examined DNA damage induced by the enediyne-containing antitumor antibiotic C
      1027 in intracellular nuclear and mitochondrial DNA targets using the episome
      containing cell line 935.1. Strand-scission activity of the C-1027 holoantibiotic
      was measured by the topological forms conversion assay in episomal and
      mitochondrial DNA, as well as in cell-free plasmid DNA. Genomic DNA damage was
      quantitated by filter elution analysis. Comparisons were made to the well
      characterized enediyne neocarzinostatin. From these studies, mixed single- and
      double-strand breaks were observed not only in cell-free, plasmid DNA but also in
      intracellular episomal, mitochondrial, and genomic DNA at low nanomolar
      concentrations. C-1027 cleaved DNA 285-fold more efficiently in cells than in a
      cell-free environment, and displayed preference for intracellular DNA species in
      the following rank order: episome > mitochondrial DNA >> genomic. NCS also
      damaged the non-histone-associated mitochondrial DNA, but not the episome.
      Cleavage of the 935.1 cell episome by C-1027 occurred at specific sites including
      the BPV origin of replication and E6/E7 open reading frame regions, as well as
      the MMTV LTR promoter region.

PMID- 7819254
TI  - Substrate and product structural requirements for binding of nucleotides to H-ras
      p21: the mechanism of discrimination between guanosine and adenosine nucleotides.
AB  - The interaction of the protein product of the H-ras oncogene with a series of
      nucleoside di- and triphosphates has been examined to investigate the tolerance
      of the active site to departures from the GTP or GDP structures. Nucleotides
      which bind relatively strongly could be used as competitors of GDP in a simple
      filter binding assay to give semiquantitave estimates of their affinities. For
      more weakly binding nucleotides or to obtain quantitative data, a transient
      kinetic method was used which was based on determination of the association and
      dissociation rate constants. The results obtained indicate that substantial
      modification of the sugar or phosphate structure is tolerated with little or
      moderate loss of affinity, but that large losses in affinity occur on
      modification of the base structure. In particular, replacing the guanine by an
      adenine residue leads to a dramatic loss of affinity. Thus, discrimination
      against ATP and ADP is very high (relative affinities of ATP and GTP 1:10(7)).
      This is due not only to loss of positive (stabilizing) interactions, but
      especially to the introduction of negative ones.

PMID- 7819255
TI  - 1H NMR investigation of the paramagnetic cluster environment in Pyrococcus
      furiosus three-iron ferredoxin: sequence-specific assignment of ligated cysteines
      independent of tertiary structure.
AB  - One- and two-dimensional 1H NMR data tailored to detect paramagnetically relaxed
      protons near the S = 1/2, three-iron-sulfur cluster of the ferredoxin from the
      hyperthermophile Pyrococcus furiosus are analyzed to sequence specifically assign
      the hyperfine shifted ligated cysteine signals, to determine the nature of the
      secondary structural elements on which these cysteines reside, and to define the
      tertiary contacts of the cluster with the remainder of the previously
      characterized secondary structure remote from the cluster [Teng, Q., Zhou, Z.-H.,
      Busse, S.C., Howard, J.B., Adams, M. W. W., & La Mar, G. N. (1994) Biochemistry
      33, 6316-6326]. Inspection of the geometry of the cluster ligating cysteines in
      the six structurally characterized cubane ferredoxin (Fd) clusters reveals a
      pattern of distances from the cluster iron(s) that indicate that each Cys will
      exhibit one backbone proton that will allow the detection of dipolar
      connectivities to the backbone of adjacent residues. It is expected that the
      first and last of the Cys in the cluster consensus binding sequence will exhibit
      weakly relaxed peptide NH and strongly relaxed C alpha H signals, while the two
      central Cys in that sequence will exhibit strongly relaxed peptide NH but weakly
      relaxed C alpha H peaks. These dipolar contacts are clearly observed for the
      three ligated Cys in 3Fe P. furiosus Fd, providing the first sequence specific
      assignment of ligated cysteines which do not explicitly require knowledge of the
      tertiary structure of the protein. This approach is proposed to have very general
      application to cubane ferredoxins. A combination of steady-state NOEs and short
      mixing time NOESY experiments demonstrate that Cys17 is on a short helix through
      Leu20 and that Cys56 likely initiates a type I turn, as observed in the crystal
      structure of the 3Fe Fd for Desulfovibrio gigas [Kissinger, C. R., Sieker, L. C.,
      Adman, E. T., & Jensen, L. H. (1991) J. Mol. Biol. 219, 693-715]. The observed
      relaxation rates of resolved or partially resolved signals are shown to correlate
      with their proximity to the various iron in the cluster, as determined for the
      homologous residues in D. gigas Fd, providing additional qualitative information
      on tertiary contacts of the cluster.

PMID- 7819256
TI  - Comparison of the hydrogen-exchange behavior of reduced and oxidized Escherichia
      coli thioredoxin.
AB  - Hydrogen-deuterium exchange rates for the amide protons in oxidized (disulfide)
      and reduced (dithiol) thioredoxin have been measured using a series of 15N-1H
      HSQC spectra at various times after buffer exchange into 99% 2H2O. Information on
      exchange rates and protection factors was obtained for both forms of thioredoxin
      for 68 amide protons using this method; in general, the rates obtained by this
      method were for amide protons of residues in the hydrogen-bonded beta-sheet and
      alpha-helix secondary structure of thioredoxin. Estimates of the exchange rate
      for those amide protons that exchanged with rates too fast to measure by hydrogen
      -deuterium exchange were made by saturation-transfer measurements, which were
      particularly useful in defining the hydrogen exchange behavior of the active site
      Cys-Gly-Pro-Cys sequence and of the loops adjacent to it (residues 73-75 and 91
      98). Amide proton exchange rates provide a qualitative estimate of the backbone
      mobility, and the differences in hydrogen exchange behavior between the two forms
      of thioredoxin are consistent with those observed in calculations of polypeptide
      chain dynamics obtained from 15N relaxation measurements [Stone, M. J., et al.
      (1993) Biochemistry 32, 426-435]. For most of the protein, the exchange rates are
      close to identical in the two forms, consistent with their very close similarity
      in structure and backbone dynamics. Significant differences in behavior are
      observed in the active site sequence and in the regions of the protein that are
      close to this sequence in the three-dimensional structure, including portions of
      the beta-strand and alpha-helical sequences immediately adjacent to the active
      site.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7819257
TI  - Three-dimensional solution structure of Callinectes sapidus metallothionein-1
      determined by homonuclear and heteronuclear magnetic resonance spectroscopy.
AB  - Metallothionein is a cysteine-rich metal-binding protein whose biosynthesis is
      closely regulated by the level of exposure of an organism to zinc, copper,
      cadmium, and other metal salts. The metallothionein from Callinectes sapidus is
      known to bind six divalent metal ions in two separate metal-binding clusters.
      Heteronuclear 1H-113Cd and homonuclear 1H-1H NMR correlation experiments have
      been used to establish that the two clusters reside in two distinct protein
      domains. The three-dimensional solution structure of the metallothionein has been
      determined using the distance and angle constraints derived from these two
      dimensional NMR data sets and a distance geometry/simulated annealing protocol.
      There are no interdomain short distance (< or = 4.5 A) constraints observed in
      this protein, enabling the calculation of structures for the N-terminal, beta
      domain and the C-terminal, alpha domain separately. A total of 18 structures were
      obtained for each domain. The structures are based on a total of 364 experimental
      NMR restraints consisting of 277 approximate interproton distance restraints, 12
      chi 1 and 51 phi angular restraints, and 24 metal-to-cysteine connectivities
      obtained from 1H-113Cd correlation experiments. The only element of regular
      secondary structure in either of the two domains is a short segment of helix in
      the C-terminal alpha domain between Lys42 and Thr48. The folding of the
      polypeptide backbone chain in each domain, however, gives rise to several type I
      beta turns. There are no type II beta turns.

PMID- 7819258
TI  - Thermodynamic study of the pH-dependent interaction of chromogranin A with an
      intraluminal loop peptide of the inositol 1,4,5-trisphosphate receptor.
AB  - The secretory vesicles of adrenal chromaffin cells have previously been
      identified as a major inositol 1,4,5-trisphosphate (IP3)-sensitive Ca2+ store,
      and their Ca2+ store role has been attributed to the presence of chromogranin A,
      a high capacity, low affinity Ca2+ binding protein. Chromogranin A has since been
      shown to exist primarily in a dimeric state at pH 7.5 and primarily in a
      tetrameric state at the intravesicular pH of 5.5 and has also been shown to
      interact with the membrane proteins of secretory vesicles at pH 5.5, including a
      260-kDa protein reactive to IP3 receptor antibody [Yoo, S. H. (1994) J. Biol.
      Chem. 269, 12001-12006]. In a recent study, chromogranin A was shown to interact
      with one of the intraluminal loop regions of the IP3 receptor at pH 5.5 but not
      at pH 7.5 [Yoo, S. H., & Lewis, M. S. (1994) FEBS Lett. 341, 28-32]. To gain
      further insight, we have studied the temperature dependence of the pH-dependent
      interaction of chromogranin A with the intraluminal peptide of the the IP3
      receptor by analytical ultracentrifugation, using multiwavelength scan analysis,
      and found that four molecules of the intraluminal domain peptide of the IP3
      receptor bound to each chromogranin A tetramer with delta Go values ranging from 
      23.6 to -27.6 kcal mol-1 in the absence and presence of 35 mN Ca2+.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7819259
TI  - Interaction of the nuclear GTP-binding protein Ran with its regulatory proteins
      RCC1 and RanGAP1.
AB  - The guanine nucleotide dissociation and GTPase reactions of Ran, a Ras-related
      nuclear protein, have been investigated using different fluorescence techniques
      to determine how these reactions are stimulated by the guanine nucleotide
      exchange factor RCC1 and the other regulatory protein, RanGAP1 (GTPase-activating
      protein). The intrinsic GTPase of Ran is one-tenth of the rate of p21ras and is
      even lower in the Ran(Q69L) mutant. Under saturating conditions the rate constant
      for the RanGAP1 stimulated GTPase reaction is 2.1 s-1 at 25 degrees C, which is a
      10(5)-fold stimulation, whereas RanGAP1 has no effect on Ran(Q69L). The intrinsic
      guanine nucleotide dissociation rates of Ran are also very low and are likewise
      increased 10(5)-fold by the exchange factor RCC1. Methods to describe the
      reaction kinetically are presented. The Ran(T24N) mutant, which is analogous to
      the S17N mutant of p21ras, has decreased relative affinities for both GDP/GTP and
      favors GDP binding. However, it was found to interact almost normally with RCC1.
      The combination of these properties leads to stabilization of the Ran(T24N)-RCC1
      complex and may result in vivo in depletion of RCC1 available for stimulating
      guanine nucleotide exchange.

PMID- 7819260
TI  - Identification of N2-(1-carboxyethyl)guanine (CEG) as a guanine advanced
      glycosylation end product.
AB  - Reducing sugars such as glucose react nonenzymatically with protein amino groups
      to initiate a posttranslational modification process known as advanced
      glycosylation. Nucleotide bases also participate in advanced glycosylation
      reactions, producing DNA-linked advanced glycosylation endproducts (AGEs) that
      cause mutations and DNA transposition. Although several protein-derived AGEs have
      been isolated and structurally characterized, AGE-modified nucleotides have not
      yet been reported. We systematically examined the reactivities of the model
      nucleotide bases 9-methylguanine (9-mG), 9-methyladenine (9-mA), and 1
      methylcytosine (1-mC) toward glucose and several glucose-derived reactants. In
      "fast" reactions performed at refluxing temperature and physiological pH, 1 equiv
      of nucleotide base was reacted with 10 equiv of D-glucose, D-glucose 6-phosphate
      (G-6-P), D-glucose 6-phosphate/lysine (G-6-P/Lys), the Schiff base 1-n
      propylamino-N-D-glucoside (SB), or the Amadori product 1-n-propylamino-N-D
      fructose (AP). In every reaction involving 9-mG, N2-(1-carboxyethyl)-9
      methylguanine (CEmG) was a major product which was produced. N2-(1-carboxyethyl)
      9-methylguanine also formed from 9-mG and AP in long-term incubations performed
      at 37 degrees C. Direct treatment of 9-mG with methylglyoxal (MG), a Maillard
      reaction propagator that forms from the decomposition of AP, also produced CEmG
      in high yield. N2-(1-Carboxyethyl)-9-methylguanine appears to result from the
      nucleophilic addition of the primary amino group of guanine to the ketone group
      of MG followed by an intramolecular rearrangement. Methylglyoxal is a known
      prokaryotic mutagen and was shown additionally to be mutagenic in a eukaryotic
      shuttle vector assay system.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7819261
TI  - A DNA aptamer that binds adenosine and ATP.
AB  - We have used in vitro selection to isolate adenosine/ATP-binding DNA sequences
      from a pool of approximately 2 x 10(14) different random-sequence single-stranded
      DNA molecules. One of these aptamers has been characterized and binds adenosine
      in solution with a dissociation constant of 6 +/- 3 microM. Experiments with ATP
      analogs indicate that functional groups on both the base and the sugar of ATP are
      involved in the ligand/aptamer interaction. The binding domain of this aptamer
      was localized to a 42 base sequence by deletion analysis. A pool of mutagenized
      versions of this sequence was then synthesized and screened for functional
      adenosine binding sequences; comparison of the selected variants revealed two
      highly conserved guanosine-rich regions, two invariant adenosine residues, and
      two regions of predominantly Watson--Crick covariation. This data led us to
      propose a model of the ATP-binding DNA structure which is based on a stable
      framework composed of two stacked G-quartets. The two highly conserved adenosine
      residues may stack between the top G-quartet and the two short stems, forming a
      pocket in which the adenosine or ATP ligand binds. Site-directed mutagenesis,
      base analog substitution studies, and the design of highly divergent but
      functional sequences provide support for this model.

PMID- 7819262
TI  - Tests of a model of specific contacts in T7 RNA polymerase-promoter interactions.
AB  - The T7, T3, and SP6 RNA polymerases represent a highly homologous family of
      enzymes that recognize similarly homologous promoter DNA sequences. Despite these
      similarities, the enzymes are highly specific for their respective promoters.
      Studies of mutant RNA polymerases have linked a specific amino acid residue in
      the protein to recognition of bases at positions -11 and -10 in the promoter
      [Raskin, C. A., et al. (1992) J. Mol. Biol. 228, 506-515]. In kinetic analyses of
      transcription from synthetic promoters containing base-analog substitutions, we
      have recently shown that at positions -11 and -10 of the T3 promoter, T3 RNA
      polymerase recognizes functional groups along the nontemplate strand wall of the
      major groove [Schick, C., & Martin, C. T. (1993) Biochemistry 32, 4275-4780]. We
      now extend these studies to the homologous region of the T7 promoter. The results
      confirm extrapolations from the T3 system and show that T7 RNA polymerase
      recognizes corresponding functional groups at positions -11 and -10 of the T7
      promoter. The results are consistent with a direct readout model for recognition
      of these bases [Raskin, C. A., et al. (1992) J. Mol. Biol., 228, 506-515], in
      which the 6-carbonyl and 7-imino groups of the nontemplate guanine at position 
      11 and the 6-amino group of the nontemplate adenine at position -10 of the T7
      promoter are directly involved in binding. The results further support an overall
      model for promoter recognition in which the enzyme binds to one face of the
      duplex DNA in this upstream region of the promoter.

PMID- 7819264
TI  - Mg2+ binding to the active site of EcoRV endonuclease: a crystallographic study
      of complexes with substrate and product DNA at 2 A resolution.
AB  - The type II restriction endonuclease EcoRV was crystallized as a complex with the
      substrate DNA undecamer AAAGATATCTT (recognition sequence underlined). These
      crystals diffract to much better resolution (2 A) than was the case for the
      previously reported complex with the decamer GGGATATCCC [Winkler, F. K., Banner,
      D. W., Oefner, C., Tsernoglou, D., Brown, R. S., Heathman, S. P., Bryan, R. K.,
      Martin, P. D., Petratos, K., & Wilson, K. S. (1993) EMBO J. 12, 1781-1795]. The
      crystal structure contains one dimer complex in the asymmetric unit and was
      solved by molecular replacement. The same kinked DNA conformation characteristic
      for enzyme-bound cognate DNA is observed. Crystals, soaked with Mg2+, show the
      essential cofactor bound at only one active site of the dimer, and the DNA is not
      cleaved. The Mg2+ has one oxygen from the scissile phosphodiester group and two
      carboxylate oxygens, one form Asp74 and one from Asp90, in its octahedral ligand
      sphere. The scissile phosphodiester group is pulled by 1 A toward the Mg2+. After
      substrate cleavage in solution, isomorphous crystals containing the enzyme-
      product--Mg2+ complex were obtained. In this structure, each of the 5'-phosphate
      groups is bound to two Mg2+. The kinked DNA conformation is essentially
      maintained, but the two central adenines, 3' to the cleavage sites, form an
      unusual cross-strand base stacking. The structures have been refined to R factors
      of 0.16 at 2.1-2.0 A resolution maintaining very good stereochemistry. On the
      basis of these structures and inspired by recent kinetic data [Vipond, I. B., &
      Halford, S. E. (1994) Biochemistry (second paper of three in this issue)], we
      have constructed a transition state model with two metals bound to the scissile
      phosphorane group.

PMID- 7819263
TI  - Topological transformations of synthetic DNA knots.
AB  - Two synthetic DNA molecules that can be knotted have been employed as substrates
      for E. coli DNA topoisomerases I and III. Both molecules contain 104 nucleotides,
      including sequences that can form two single-turn helical domains, connected by
      single-stranded oligo(dT) linkers in an X-Y-X'-Y' pairing motif. One of the knots
      can be ligated to form cyclic molecules with the topologies of a circle, a
      trefoil knot with negative nodes, or a figure-8 knot. Cyclic molecules
      constructed from the other molecule can form a circle, a figure-8 knot, and
      trefoil knots with either positive or negative nodes. The topologically negative
      nodes in these knots are derived from right-handed B-DNA, and the positive nodes
      are derived from left-handed Z-DNA. The topoisomerases can catalyze the
      interconversion of the different topological forms of these molecules, as a
      function of solution conditions and the extent to which they favor B-DNA or Z
      DNA. The enzymes appear to catalyze a single strand-passage event at a time. The
      topoisomerases can catalyze strand passage events involving both positive and
      negative nodes as substrates. Gel retention experiments show that both knots can
      bind up to four molecules of E. coli DNA topoisomerase I. The thermal
      denaturation of the domains of a trefoil knot closely related to these knots
      suggests that the two helical domains are uncoupled, so the single-stranded
      linkers in the knots are not taut. Chemical ligation experiments yield a
      distribution of products similar to those of enzymatic ligation, showing that the
      ATP cofactor in DNA knot ligation does not appear to skew the products markedly.
      Knots that are stressed by being placed in unfavorable solution conditions have
      been shown to be a highly sensitive system for detecting topoisomerase activity.

PMID- 7819265
TI  - Divalent metal ions at the active sites of the EcoRV and EcoRI restriction
      endonucleases.
AB  - Restriction enzymes cannot cleave DNA without a metal ion cofactor. The
      specificities of the EcoRV and EcoRI endonucleases for metals were studied by
      measuring DNA cleavage rates with several metal ions and with combinations of
      metal ions. Both EcoRV and EcoRI had optimal activities with Mg2+, were less
      active with several other ions including Mn2+, and had virtually no activity with
      Ca2+. But the activities of EcoRV and EcoRI with either Mg2+ or Mn2+ were
      perturbed by Ca2+. For EcoRI, both Mg2+- and Mn(2+)-dependent activities, at both
      cognate and noncognate sites, were all inhibited by Ca2+. The activity of EcoRV
      at its recognition site with Mg2+ was also inhibited by Ca2+. But the Mn(2+)
      dependent reaction at the EcoRV recognition site was stimulated by Ca2+. EcoRV
      activities at noncognate sites with either Mg2+ or Mn2+ displayed a biphasic
      response to Ca2+: stimulation at low concentrations of Ca2+ and inhibition at
      high concentrations. These observations, together with the known structures of
      the proteins, indicate that EcoRI needs only one metal ion per active site and is
      inactive when Mg2+ is displaced by Ca2+, while EcoRV needs two and that the
      displacement of one by Ca2+ can enhance activity. We propose a mechanism for
      phosphodiester hydrolysis by EcoRV that involves two metal ions.

PMID- 7819266
TI  - Rapid reaction analysis of the catalytic cycle of the EcoRV restriction
      endonuclease.
AB  - We have used the intrinsic tryptophan fluorescence of the EcoRV restriction
      endonuclease to monitor changes in protein conformation during binding and
      cleavage of a duplex oligodeoxynucleotide substrate. Appropriate conditions for
      single-turnover reactions were first determined by steady-state kinetics. When
      single turnovers were monitored by stopped-flow fluorescence, the mixing together
      of EcoRV, oligonucleotide and MgCl2 resulted in a rapid increase in tryptophan
      fluorescence followed by a slow decrease. Further analysis by order-of-mixing and
      quench experiments showed that the transient increase in fluorescence was due to
      a conformational change coupled to DNA binding, while the subsequent decay was
      concomitant with phosphodiester hydrolysis. The rate of the latter step varied
      with the concentration of Mg2+ ions, but another Mg(2+)-dependent transition was
      observed upon the addition of MgCl2 to a preformed enzyme-DNA complex. These
      results lead to a reaction scheme in which one Mg2+ binds to the active site
      prior to phosphodiester hydrolysis but a second Mg2+ is then needed to carry out
      the hydrolytic reaction. This scheme is correlated to the crystal structures of
      the EcoRV endonuclease and its complexes with DNA and Mg2+ ions.

PMID- 7819267
TI  - Glycoconjugates in autoimmunity.

PMID- 7819268
TI  - Phospholipid trafficking and membrane biogenesis.

PMID- 7819269
TI  - Protein translocation in Escherichia coli.

PMID- 7819270
TI  - Somatic genetic changes in human breast cancer.
AB  - Quantitative imbalance in chromosomal material relative to the normal diploid
      situation is the most conspicuous genetic change in breast tumors, affecting
      virtually all chromosomes in varying frequencies. This imbalance is reflected by
      deviant DNA stemlines observed in DNA flow cytometry analysis, by numerical
      chromosome abnormalities in karyotype analysis and by loss of heterozygosity in
      DNA polymorphism studies. Gene amplification might be caused by the same genetic
      mechanisms that cause these chromosomal abnormalities [134]. The number of known
      genes for which there is now good evidence for their role in the development of
      breast cancer is still limited, and basically restricted to TP53 and ERBB2.
      Clearly, the estrogen receptor, not discussed here, can be conjectured to be of
      importance in breast cancer development, yet the significance of the reported
      sequence variants [157] for hormone-independent growth is presently undetermined
      [158]. For many others, such as MYC, CCND1, EMS1, EGF, RB1, NME, DCC and
      prohibitin, the evidence is still largely circumstantial, or obtained only by in
      vitro studies on breast cancer cell lines. In many cases of chromosomal imbalance
      and certainly those affecting whole chromosomes or chromosome arms, it is unclear
      what their effect on tumor growth will be, because multiple potential candidate
      genes are located in the affected region. In addition, it is obvious that
      multiple chromosomes are affected simultaneously in a single tumor, but that the
      total set of chromosome changes varies in different tumors. This intra- and
      intertumor heterogeneity of chromosome involvement suggests that an unknown
      number of the observed abnormalities are not important for tumor development, but
      merely result from genetic instability. On the other hand, there is accumulating
      evidence, particularly from flow cytometry and allelotype studies reviewed here,
      to suggest that the genetic evolution associated with tumor development and
      progression does reach a stage of equilibrium despite the presence of extensive
      tumor heterogeneity. The number of genetic events found per tumor raises the
      question whether each event of heterozygosity loss represents the second step in
      the inactivation of a tumor suppressor gene. Also, LOH observed with polymorphic
      markers can sometimes be interpreted as allelic copy number gain instead of loss.
      Possibly, some of these allelic imbalances contribute to the tumorigenic process
      simply because they create a dosage effect in certain gene products [2]. This
      supposes that the sole presence of allelic imbalance at certain chromosomes is
      sufficient to provide selective growth advantage in certain cases.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7819271
TI  - The role of p21ras in receptor tyrosine kinase signalling.

PMID- 7819272
TI  - Spi-1/PU.1: an oncogene of the Ets family.

PMID- 7819273
TI  - The biology of erbB-2/neu/HER-2 and its role in cancer.

PMID- 7819274
TI  - Growth factor-like effects of lysophosphatidic acid, a novel lipid mediator.

PMID- 7819275
TI  - p53 and the Li-Fraumeni syndrome.

PMID- 7819276
TI  - The G1/S cell-cycle checkpoint in eukaryotic cells.

PMID- 7819277
TI  - Defining origins of replication in mammalian cells.

PMID- 7819278
TI  - Contribution of mutant analysis to the understanding of enzyme catalysis: the
      case of class A beta-lactamases.
AB  - Class A beta-lactamases represent a family of well studied enzymes. They are
      responsible for many antibiotic resistance phenomena and thus for numerous
      failures in clinical chemotherapy. Despite the facts that five structures are
      known at high resolution and that detailed analyses of enzymes modified by site
      directed mutagenesis have been performed, their exact catalytic mechanism remains
      controversial. This review attempts to summarize and to discuss the many
      available data.

PMID- 7819279
TI  - Conformational structure of bombesin as studied by vibrational and circular
      dichroism spectroscopy.
AB  - Raman and Fourier transform infrared (FTIR) spectroscopies and circular dichroism
      (CD) have been applied to investigate the secondary structure of bombesin in the
      solid state and in phosphate buffer solution (pH 3.8). At concentrations around
      10(-5) M, circular dichroism reveals that bombesin exists as an irregular or
      disordered conformation. However, the secondary structure of the peptide appears
      to be a mixture of disordered structure and intermolecular beta-sheets in 0.01 M
      sodium phosphate buffer when the peptide concentrations are higher than around
      6.5 mM. The tendency of bombesin to form aggregated beta-sheet species seems to
      be originated mainly in the sequence of the residues 7-14, as supported by the
      Raman spectra and beta-sheet propensities (P beta) of the amino-acid residues. It
      is the hydrophobic force of this amino-acid sequence, and not a salt bridge
      effect, that is the factor responsible for the formation of peptide aggregates.

PMID- 7819280
TI  - Cadmium-113 and magnesium-25 NMR study of the divalent metal binding sites of
      isocitrate dehydrogenases from pig heart.
AB  - The metal activator sites of NAD(+)-dependent and NADP(+)-dependent isocitrate
      dehydrogenases from pig heart have been probed using 113Cd- and 25Mg-NMR. In the
      presence of isocitrate and ADP, a broad resonance for cadmium bound to NAD
      dependent isocitrate dehydrogenase was observed (-8 ppm) arising from exchange
      with isocitrate (-20 ppm) and/or ADP (27 ppm) complexes. The Cd shift with ADP
      suggests interaction of the metal with the nucleotide ring nitrogen. Increasing
      shifts with excess ADP are indicative of macrochelate formation. 25Mg-NMR
      demonstrates that, unlike manganese, magnesium has a similar dissociation
      constant (1.8 mM) from NADP-dependent isocitrate dehydrogenase as from the enzyme
      isocitrate complex (1.1 mM). The extrapolated line width of bound magnesium
      increases from 674 Hz in the binary complex to 10,200 Hz in the ternary complex.
      The quadrupole coupling constant, calculated from relaxation rates, is larger in
      the ternary complex, indicative of greater distortion in the magnesium
      coordination sphere. The line widths of magnesium complexed to NAD-dependent
      isocitrate dehydrogenase are broader, as expected for the larger octamer. 113Cd-
      and 25Mg-NMR both show that the metal sites have anisotropic octahedral symmetry.
      25Mg relaxation rates yield correlation times corresponding to motions of a
      domain with motion independent of the enzyme multimers.

PMID- 7819281
TI  - Enzyme kinetics by mid-infrared spectroscopy: beta-fructosidase study by a one
      step assay.
AB  - An alternate method for enzyme study is proposed. Multidimensional statistical
      analysis applied on mid-infrared attenuated total reflectance spectra (Cadet et
      al. (1991) Appl. Spectrosc. 42, 166-172) collected during a kinetic allows a
      direct and fast quantification of the remaining substrate, as well as a one step
      enzymatic assay. Furthermore, the combination of these techniques may be used as
      a structural tool. The method applied to the study of beta-fructosidase is
      developed in this paper as an example. With appropriate calibration, the method
      may be extend to any enzyme.

PMID- 7819282
TI  - ADP-ribosylation reactions in Sulfolobus solfataricus, a thermoacidophilic
      archaeon.
AB  - An ADP-ribosylating system was detected in a crude homogenate from Sulfolobus
      solfataricus, a thermophilic archaeon, optimally growing at 87 degrees C. The
      archaeal ADP-ribosylation reaction was time-, temperature- and NAD-dependent. It
      proved to be highly thermostable, with about 30% decrease of 14C incorporation
      from [14C]NAD on incubation at 80 degrees C for up to 24 h. The main reaction
      product was found to be mono-ADP-ribose. Testing both [adenine-14C(U)]NAD and
      [adenine-14C(U)]ADPR as substrates, it was found that acceptor proteins were
      modified by ADP-ribose both enzymatically, via ADP-ribosylating enzymes, and via
      chemical attachment of free ADP-ribose, likely produced by NAD glycohydrolase
      activity. The synthesis of ADP-ribose-protein complexes was shown to involve
      mainly acceptors with molecular masses in the 40-100 kDa range, as determined by
      electrophoresis on polyacrylamide gel in the presence of sodium dodecyl sulphate.

PMID- 7819283
TI  - Cloning and base sequence analysis of a cDNA encoding mouse lung thioether S
      methyltransferase.
AB  - Thioether S-methyltransferase catalyzes transfer of the methyl group from S
      adenosylmethionine to X in compounds of the structure R-X-R', where X may be
      sulfur, selenium, or tellurium, and R and R' may be various organic groups. To
      obtain a cDNA clone of thioether S-methyltransferase, a mouse lung cDNA library
      in lambda gt11 was screened with a 99 base-pair probe obtained by performing the
      polymerase chain reaction on oligo(dT) primed, reverse transcribed, mouse lung
      RNA using two degenerate primers designed from partial amino-acid sequences of
      the enzyme. The entire coding and 3'-untranslated regions were obtained and
      sequenced. The predicted protein contains 264 amino-acid residues and has a
      calculated M(r) of 29,460. The amino-acid sequence of thioether S
      methyltransferase contains three motifs characteristic of many methyltransferases
      and has a high level of identity with the amino-acid sequences of nicotinamide N
      methyltransferase and phenylethanolamine N-methyltransferase. However, in spite
      of the fact that they are both mammalian cytosolic sulfur methyltransferases, the
      sequences of thioether S-methyltransferase and thiopurine S-methyltransferase
      share little identity.

PMID- 7819284
TI  - Rat liver nucleoside diphosphosugar or diphosphoalcohol pyrophosphatases
      different from nucleotide pyrophosphatase or phosphodiesterase I: substrate
      specificities of Mg(2+)-and/or Mn(2+)-dependent hydrolases acting on ADP-ribose.
AB  - Three rat liver nucleotides(5') diphosphosugar (NDP-sugar) or nucleoside(5')
      diphosphoalcohol pyrophosphatases are described: two were previously identified
      in experiments measuring Mg(2+)-dependent ADP-ribose pyrophosphatase activity
      (Miro et al. (1989) FEBS Lett. 244, 123-126), and the other is a new, Mn(2+)
      dependent ADP-ribose pyrophosphatase. They are resolved by ion-exchange
      chromatography, and differ by their substrate and cation specificities, KM values
      for ADP-ribose, pH-activity profiles, molecular weights and isoelectric points.
      The enzymes were tested for activity towards: reducing (ADP-ribose, IDP-ribose)
      and non-reducing NDP-sugars (ADP-glucose, ADP-mannose, GDP-mannose, UDP-mannose,
      UDP-glucose, UDP-xylose, CDP-glucose), CDP-alcohols (CDP-glycerol, CDP
      ethanolamine, CDP-choline), dinucleotides (diadenosine pyrophosphate, NADH, NAD+,
      FAD), nucleoside(5') mono- and diphosphates (AMP, CMP, GMP, ADP, CDP) and dTMP p
      nitrophenyl ester. Since the enzymes have not been purified to homogeneity, more
      than three pyrophosphatases may be present, but the co-purification of
      activities, thermal co-inactivation, and inhibition experiments give support to:
      (i) and ADP-ribose pyrophosphatase highly specific for ADP(IDP)-ribose in the
      presence of Mg2+, but active also on non-reducing ADP-hexoses and dinucleotides
      (not on NAD+) when Mg2+ was replaced with Mn2+; (ii) a Mn(2+)-dependent
      pyrophosphatase active on ADP(IDP)-ribose, dinucleotides and CDP-alcohols; (iii)
      a rather unspecific pyrophosphatase that, with Mg2+, was active on AMP(IMP)
      containing NDP-sugars and dinucleotides (not on NAD+), and with Mn2+, was also
      active on non-adenine NDP-sugars and CDP-alcohols. The enzymes differ from
      nucleotide pyrophosphatase/phosphodiesterase-I (NPPase/PDEaseI) by their
      substrate specificities and by their cytosolic location and solubility in the
      absence of detergents. Although NPPase/PDEaseI is much more active in rat liver,
      its known location in the non-cytoplasmic sides of plasma and endoplasmic
      reticulum membranes, together with the known cytoplasmic synthesis of NDP-sugars
      and CDP-alcohols, permit the speculation that the pyrophosphatases studied in
      this work may have a cellular role.

PMID- 7819285
TI  - Thermodynamic aspects of the CO-binding reaction to cytochrome P-450cam.
      Relevance with their biological significance and structure.
AB  - The CO-binding kinetics of cytochrome P-450cam(+) and P-450cam(-) have been
      measured in the millisecond time domain using a flash photolysis method. We have
      determined the reaction coordinates for free energy, enthalpy and entropy from
      the temperature dependence of the overall rate constants of the bimolecular
      forward (on) and backward (off) reactions. Comparing the thermodynamic profiles
      of P-450cam with that of myoglobin (Mb) reported so far, the enthalpy and the
      entropy coordinates exhibit the following remarkable characteristics. The CO
      binding equilibrium: The stability of the CO-complex is perfectly entropy-driven
      for P-450cam, while enthalpy-driven for Mb. This entropy-driven feature for P
      450cam is enhanced by the dissociating d-camphor. The on and off activation
      processes: The on and off reactions for P-450cam are dominantly controlled by the
      enthalpy and entropy terms, respectively, while those for Mb are rather the
      reverse of the case of P-450cam. The dissociation of d-camphor has a significant
      effect on the on reaction but no effect on the off reaction. Analyzing these
      thermodynamic features on the basis of the physical chemistry in the solution
      reaction, it was found that these characteristic profiles arise from the
      difference in the global structural change between the proteins. Namely, during
      the equilibrium process of the CO binding, this structural change is accompanied
      by a larger increase in the degree of freedom in P-450cam than in Mb. We
      discussed the correlations between the structural changes and their biological
      significance.

PMID- 7819287
TI  - Mycobacterium smegmatis malate dehydrogenase: activation of the lipid-depleted
      enzyme by anionic phospholipids and phosphatidylethanolamine.
AB  - Phospholipid-protein interactions have been investigated in a phospholipid
      requiring enzyme, FAD-dependent malate dehydrogenase isolated from Mycobacterium
      smegmatis membranes, to correlate these interactions with enzyme function. The
      ability of several natural and synthetic phospholipids including CL and PE, which
      are major phospholipids in M. smegmatis membranes, to activate purified, lipid
      depleted, enzymatically inactive malate dehydrogenase was examined. Anionic
      phospholipids and PE activated the enzyme, while zwitterionic phospholipids did
      not. A PE/PC mixture activated the enzyme in the form of both bilayer and non
      bilayer structure. CL/PE mixtures activated malate dehydrogenase much more than
      each single phospholipid species. All anionic phospholipids used stabilized the
      enzyme, while PE and zwitterionic phospholipids did not. CL and a CL/PE mixture
      protected malate dehydrogenase from proteinase digestion, while PE did not. All
      phospholipids and phospholipid mixtures tested caused little secondary structural
      change in malate dehydrogenase. The results obtained in this study suggest that
      CL and CL/PE mixtures could form stable, enzymatically active complexes with
      malate dehydrogenase which might be similar to the native complex in M. smegmatis
      membranes. Although PE could activate malate dehydrogenase in both bilayer and
      non-bilayer form, it formed a complex with malate dehydrogenase which was
      inferior in terms of stability and susceptibility to proteinases, indicating that
      PE alone poorly reconstitutes the active enzyme-phospholipid complex.

PMID- 7819286
TI  - Amyloid precursor protein is not processed by furin, PACE 4, PC1/3, PC2, PC4 and
      PC5/6 of the furin family of proprotein processing enzymes.
AB  - Proteolytic cleavage of the amyloid precursor protein (APP) has previously been
      shown to release its extracellular domain into the medium. The identification of
      the responsible proteinase(s), termed secretase(s), is a high priority in ongoing
      Alzheimer research. This is hampered by the unusual characteristics of these
      enzyme(s) and by the fact that they cleave only membrane associated APP. We
      report here, using a vaccinia virus based expression system, that pig kidney
      PK(15) cells express full-length, membrane bound APP695, but that secretion of
      APP is low. This heterologous expression system allows to assay candidate
      secretases in a cellular context by simple co-transfection of the APP and
      candidate secretase cDNA containing plasmids. Eight different members of the
      mouse and human furin family of proprotein processing enzymes were tested in this
      assay, but none of them enhanced the secretion of APP. Secretion of von
      Willebrand's factor was used as a positive control.

PMID- 7819288
TI  - Isolation and sequence analysis of the gene for arginine kinase from the
      chelicerate arthropod, Limulus polyphemus: insights into catalytically important
      residues.
AB  - The gene for arginine kinase (AK; EC 2.7.3.3) from the horseshoe crab, Limulus
      polyphemus, was cloned and the complete cDNA sequence was determined. An open
      reading frame with 1071 nucleotides was detected that encodes a 357 amino-acid
      protein with a calculated M(r) of 40,238. The coding transcript is flanked by 13
      and 512 nucleotides of 5' and 3' untranslated regions, respectively. The deduced
      amino-acid sequence of Limulus AK displays extensive similarity to other arginine
      kinases, vertebrate and invertebrate creatine kinases (CK) and a glycocyamine
      kinase (GK). Consensus AK and consensus CK sequences, as well as a GK sequence,
      were compared to CK peptide regions containing residues presumed to be important
      in catalysis and/or located in close proximity to the active site. Our
      comparisons revealed some inconsistencies with hypothesized roles of particular
      residues in catalytic function.

PMID- 7819289
TI  - [Basic principles of vascular imaging with spiral CT].
AB  - Vascular investigations by CT have experienced a decisive advance and found a
      high acceptance since the introduction of fast volume scanning (spiral CT). We
      have investigated the underlying physical foundations and optimized the
      operational aspects of the method now introduced as CT angiography (CTA).
      Investigations are carried out with a table feed of 1-10 mm/s. Images are
      reconstructed at 1-2 mm separations by use of algorithms which optimize the layer
      profile. The parameters must be adapted to the region being investigated. The
      diagnosis is generally made with interactive cine runs; for this the original
      images, multiplanar reformations, 3D surface shaded displays (SSD), and maximum
      intensity projection (MIP) images are used. The 3D representations are discussed
      in the context of the principle and illustrative examples. Important applications
      for CTA are the evaluation of aortic aneurysms and dissections, pulmonary
      vessels, renal arteries, and vessel stents. CTA is characterized by short
      examination times, low invasiveness, and relatively low cost; in typical cases it
      is associated with an effective dose of 2-10 mSv. The advantages and
      disadvantages of the new method are discussed in terms of diagnostic value, image
      quality, patient dose, contrast medium techniques, and practical aspects in
      comparison to other angiographic methods.

PMID- 7819290
TI  - [Comments on the topic of determining mean optical density in roentgen images].
AB  - The determination of the mean optical density in an X-ray film by means of an
      integral measurement with a photometer at long distances from the radiograph
      yields values which are too low for the high contrasts in a few portions of the
      image. By arithmetic comparison with the true mean optical density as computed by
      a scan measurement, one can obtain a correction quantity delta D, which, in the
      extreme case, can increase up to a value of 0.7 and has to be added to the result
      of the integral measurement. Because the mean optical density has an influence on
      the image quality and therefore on the diagnostic value of a radiograph, this
      correction has to be taken into account in practice and especially at
      measurements in the "Arztliche Stellen". These institutions are authorized by the
      BAK to check the radiographs made by practitioners and radiologists for a
      sufficient image quality.

PMID- 7819291
TI  - [Status and perspectives of medical technology according to the 1993 public
      health structure regulation].
AB  - The German Health Care System is internationally recognized as having a high
      quality and efficiency for the total population. Rising costs of the Statutory
      Sickness Funds burden the employers and the employees in the same way. With the
      Health Structure Reform Act of January 1, 1993, federally induced systems for
      restructuring in part and for creating more competition are aimed to limit
      further growth rates of compulsory health insurance to a reasonable amount. The
      regulations with respect to electromedical devices and large, hightech systems
      are discussed in detail. But in the health care system technical progress also
      stimulates efficiency, initiates rationalisation, and contributes to a saving in
      costs.

PMID- 7819292
TI  - [Quality, value and risks of pelvic/ leg angiography before PTA (percutaneous
      transluminal angioplasty)].
AB  - This study evaluates the diagnostic value and image quality of 183 angiographies
      performed prior to angioplasty. 56% of the examinations were by arterial and 42%
      by intravenous DSA. Both techniques were underestimating mild and overestimating
      severe stenoses. With arterial DSA, 42% of the images in the iliac, 63% in the
      femoropopliteal, and 53% in the crural region showed an excellent quality. With
      venous DSA, these percentages were 31%, 47%, and 8%, respectively. Newly
      occurring occlusions were observed in the iliac region in 8%, and in the
      femoropopliteal region in 14% of the patients. Venous DSA and other, alternative
      techniques are sufficient in stage II of POVD and after surgery. In stages III
      and IV, as well as in diabetic patients and prior to femoro-crural bypasses, an
      arterial DSA has to be performed. In appropriate lesions, the interval of time to
      the intervention should be as short as possible to avoid progression of arterial
      thrombosis.

PMID- 7819294
TI  - [Rare complications of costal cartilaginous exostoses in childhood].
AB  - Inward projecting cartilaginous exostoses of the ribs may cause severe
      complications such as laceration of the pleura, the lung or the diaphragm.
      Prophylactic excision should be considered.

PMID- 7819293
TI  - [3D-MR myelography in diagnosis of lumbar spinal nerve root compression
      syndromes. Comparative study with conventional myelography].
AB  - 65 patients with nerve root compression syndrome were examined using a new type
      of MR-technique, which is comparable to the conventional X-ray myelography. The
      results of the prospective case study were compared with previous clinical
      experiences (1). For the examinations a 1.0T whole body MR-system (Siemens
      Magnetom Impact) was used. A strong T2*-weighted 3D-FISP sequence (TR = 73 ms, TE
      = 21 ms, alpha = 7 degrees) was applied in sagittal orientation using a
      circularly polarized oval spine coil. To obtain fat suppression a frequency
      selective 1-3-3-1 prepulse was applied prior to the imaging sequence. The
      acquired 3D-data set was evaluated using a Maximum Intensity Projection (MIP)
      program. Our results confirmed earlier experiences which showed that the
      diagnostic sensitivity of 3D-MR myelography (3D-MRM) is comparable to that of
      conventional X-ray myelography. In cases of severe spinal canal stenosis and
      spondylolisthesises, and in cases of postoperative scar tissue with nerve root
      compressions, the sensitivity of the 3D-MRM is higher as compared to that of
      conventional X-ray myelography.

PMID- 7819295
TI  - [Color Doppler controlled compression therapy of puncture aneurysms--a
      noninvasive therapy concept].
AB  - After transfemoral catheterization, pseudoaneurysms can occur in about 0.1-0.05%
      of cases, especially after the use of large instruments and a faulty puncture
      technique. Today, pseudoaneurysms can be easily and accurately diagnosed with the
      help of duplex and color Doppler ultrasound. Apart from its diagnostic
      application, color Doppler ultrasound also offers a noninvasive and cheap
      alternative therapy mode as compared to surgical repair. The purpose of our study
      was to evaluate the therapeutic efficiency of an ultrasound-guided compression
      technique for postpunctional pseudoaneurysms. Over a 12-month period, nine
      patients were sonographically diagnosed with postpunctional pseudoaneurysm of the
      femoral superficial artery. The compression therapy was only applied if no
      contraindications (e.g. rupture, retroperitoneal site of the lesion, infection,
      large haematoma with suspected ischaemia, and necrosis) were present. Two of the
      nine patients were primarily excluded from therapy because of a high risk of
      rupture or a large haematoma. Five patients of the remaining seven have been
      successfully treated. In one of the unsuccessfully treated patients, only a
      partial thrombosis of the aneurysm was obtained, followed by complete spontaneous
      thrombosis 4 days later. The second compression failed because of the 4-month
      time interval between angiography and compression therapy. A successful therapy
      clearly depended on the time interval between puncture and compression. We could
      not find any significant correlation between the aneurysm volume and the duration
      of compression. Color Doppler ultrasound-guided therapy is a noninvasive easily
      applicable, and cheap alternative to surgical repair of postpunctional
      pseudoaneurysms.

PMID- 7819296
TI  - [Spiral computerized tomography of esophageal carcinoma--methodology, problems,
      results].
AB  - Computed tomography (CT) is widely recognized as a part of the routine
      preoperative staging in patients with esophageal carcinoma. Applying a tailored
      technique, CT criteria of transmural growth and infiltration of adjacent
      structures are highly accurate for estimating resectability. The size-based
      assessment of mediastinal and abdominal lymph nodes is usually reported with low
      sensitivity and specificity. Spiral technology (spiral CT) increases image
      quality by a reduction of artifacts due to respiratory motion or cardiac
      pulsation, higher anatomic detail, and peak vascular opacification throughout the
      entire examination. Thus, an improvement of diagnostic accuracy in the staging of
      esophageal carcinoma can be expected. Its targeted application and a comparison
      with the conventional technique are presented.

PMID- 7819297
TI  - [The value of various ultrasound criteria in objective assessment of acute
      reactive cholecystitis. A prospective follow-up study of ventilated intensive
      care patients].
AB  - Ultrasound of the abdomen was performed in 30 artificially respirated patients
      under intensive care conditions for 7 days per patient over a time period of 6
      months to elucidate the therapeutic value of different ultrasonographic findings
      with respect to the diagnosis "reactive acute cholecystitis". Our results show,
      that neither the detection of concrements or sludge within the gallbladder, nor
      the transient dilatation of the bile duct, nor a transient wall-thickening or the
      occurrence of a three-layered wall of the gallbladder can be interpreted as
      reliable sonographic criteria for the occurrence of an acute reactive
      cholecystitis. From this we conclude, that reactive acute cholecystitis leading
      to the indication for cholecystectomy can only be diagnosed from the combination
      of clinical and sonographic findings. However, reactive acute cholecystitis can
      almost certainly be excluded, even in obscure upper abdominal symptoms, when the
      sonogram of the gallbladder is normal.

PMID- 7819298
TI  - [Roentgen findings in spontaneous esophageal perforation (Boerhaave syndrome)].
AB  - Having experienced two cases of Boerhaave's syndrome (spontaneous rupture of the
      oesophagus), one a 42-year-old man, the other a 76-year-old woman, who both died
      of complications failing operative repair, the authors undertook a survey of the
      literature in order to evaluate the role of radiology in the detection of this
      life-threatening condition. An analysis of 118 clinically and 67 radiologically
      well-documented cases yielded pathologic findings in chest X-rays in 90% of the
      cases. Hydropneumothorax was found in 51%, pneumomediastinum in 30%, isolated
      pleural effusion in 25%, and infiltration of the parenchyma in 14% of the
      patients. In all cases it was possible to demonstrate by contrast medium-filling
      of the oesophagus with an aqueous medium.

PMID- 7819300
TI  - [Duodenum inversum in a patient with Crohn disease].
AB  - A case of Morbus Crohn is reported in which duodenum inversum was diagnosed
      incidentally. The importance of this rotational anomaly in the context of modern
      imaging methods is discussed.

PMID- 7819299
TI  - [Leiomyosarcoma of the stomach].
AB  - Leiomyosarcoma of the stomach is a rare occurrence, amounting to only 0.5-3% of
      all stomach malignancies. Because of its extragastral growth, it produce clinical
      symptoms, mostly with bleeding, only at a late stage. The decisive method of
      examination is computed tomography which demonstrates the extraluminal tumor
      lying apparently in the mesenterium with contrast medium up-take at the borders
      and central necrosis. A secure differential diagnosis to leiomyoma is not
      possible by angiography or by computed tomography; this distinction is even
      difficult by histology.

PMID- 7819301
TI  - [CT diagnosis of acute mesenteric vein thrombosis with intestinal infarction].
AB  - Imaging methods provide an important diagnostic basis to clarify mesenteric
      ischemia. Angiography is the definitive method of investigation in such cases.
      Other noninvasive methods such as ultrasonography, computed tomography, and
      magnetic resonance imaging must still prove their importance. We describe three
      cases of unspecific abdominal pain where the CT shows a mesenteric venous
      thrombosis with an infarcted bowel. The venous infarcted bowel is clearly
      demonstrated by CT when other signs for MTV such as ascites, bowel wall
      thickening, bowel dilatation, and pneumatosis intestinalis are present. CT seems
      to be a good procedure in order to identify unspecific abdominal pain as being
      caused by a vascular insufficiency.

PMID- 7819302
TI  - [Computerized tomography of perforated Meckel's diverticulum--a case report].

PMID- 7819303
TI  - [Comments on the article "Focus measurement and geometric lack of focus in
      mammography equipment"].

PMID- 7819304
TI  - [The effect of water and secondary structure on the thermal stability of
      macroradicals in proteins].
AB  - The thermostability of macroradicals located in the protein peptide chain
      segments with the different secondary structure was investigated. It has been
      shown at the dry proteins that just the secondary structure determines the
      thermostability of the macroradicals. In the different proteins the
      thermostability of macroradicals in peptide chain segments with identical
      secondary structure is the same. The thermostability of free radicals is the same
      in aqueous solutions of the different proteins.

PMID- 7819305
TI  - [The complex of aspartate aminotransferase with D-aspartate].
AB  - We report here the x-ray studies of the complex cytosolic aspartate
      aminotransferase from chicken heart with D-aspartate at 2,7 A resolution.
      Crystals of the complex was prepared by diffusing D-aspartate into free enzyme
      crystals; their space group is P 2(1)2(1)2(1) with cell dimensions (A): a =
      62.59; b = 117.83; c = 124.38. They contain one dimeric molecule in the
      asymmetric unit. The x-ray crystallographic analysis proves that the connection
      of the D-aspartate induces small conformational changes in the active site of two
      subunits of the enzyme: considerable conformational changes are determined for
      His 189, Phe 360, Tyr 70, Arg 292, Phe 18 and Glu 141.

PMID- 7819306
TI  - [Study of the spatial organization of the globular fragment of calmodulin. I.
      Conformational analysis of the domain structure].
AB  - Theoretical conformational analysis of dodecapeptide "loop" of one of four
      domains of CaM is carried out. It's shown that one of the lowest energy
      conformations of the "loop" can bring about together E(i)- and F(i)-hands till
      van-der-waals contacts. Predominance and advantages of the calculated
      conformations are discussed in connection with structural organization of the
      domains and their capability to bind Ca(2+)-ions. The proposed "alpha-hairpin"
      structure of the domains is a part of a supersecondary structure of globular lobe
      of CaM.

PMID- 7819307
TI  - [A comparative study of the thermal stability of phenylalanyl tRNA synthetase
      from Escherichia coli MRE-600 and Thermus thermophilus HB 8].
AB  - The thermal stability of phenylalanyl-tRNA-synthetase (PTS) from E. coli and
      T.thermophilus HB 8 was studied in solution at various conditions by scanning
      microcalorimetry. It has been shown that the value of heating rate, concentration
      of the enzyme and Mg2+ ions in the solution affects the parameters of thermal
      denaturation of both enzymes. The higher thermal stability of PTS from T.
      thermophilus was observed as well as the independence of its properties upon
      broad variations of experimental conditions. The role of thermostability of the
      enzymes are discussed with respect to the biological properties of E. coli and
      T.thermophilus.

PMID- 7819308
TI  - [New data on heat denaturation of collagen fibrils].
AB  - Using the differential scanning calorimetry we have found that the structural
      changes due to the aging have the influence on the temperatures of denaturation
      and the values of denaturation heats of the intact collagen (rat tail tendon).
      The magnitude of the specific heat jump at denaturation of the collagen fibrills
      differs from that for the isolated molecules.

PMID- 7819309
TI  - [Study of DNA damage and heterogeneity of cells by a gel microelectrophoresis
      method].
AB  - The influence of some cell parameters--cell size, cell DNA content, cell cycle
      phase--on migration of DNA from individual cell in constant electric field was
      studied on human peripheral lymphocytes and mouse lymphoblasts L5178Y by
      microelectrophoresis (neutral DNA-comet assay). It has been shown that the full
      comet length (l) did not depend on the cell parameters for intact and moderately
      irradiated cells (up to 25 Gy). It is proposed that migration capacity of DNA is
      related with damage to DNA. Then the heterogeneity of intact cells in the comet
      length can mirror the variation of background level of DNA lesions from cell to
      cell in the same population. Lymphoblasts of radiosensitive strain (LY-S cells)
      show higher average DNA-mobility and heterogeneity in DNA-comet length as
      compared to the cells of radioresistant strain (LY-R). This difference is
      suggested to be compatible with relatively higher background DNA-breakage in LY-S
      cells due to deficiency in repair of double-strand breaks in these cells. A
      subpopulation (about 20%) in LY-S cells with very migrating DNA was determined
      with neutral DNA-comet assay. It is reasonable to identify this subpopulation
      with cells of this line showing the lowest DNA repair rate. Thus neutral DNA
      comet assay can be useful for evaluation of damage to and repair of DNA in
      individual cells and their heterogeneity.

PMID- 7819310
TI  - [Statistical analysis of electron microphotographs of bioobjects, labelled by
      electron-dense mercarbide markers].
AB  - A method of statistical processing of electron micrographs of molecular objects
      modified by electron-dense labels containing mercury is proposed. The method
      allows one to study size, degree of modification and heterogeneity of objects.
      Application of the method for study of modified nitrogenase and its Fe-Mo
      containing co-factor, lysozyme, myoglobin, sodium thiomolybdate and
      trichlortriazine has shown the features of chemical modification and electron
      micrographs of these molecules. The method can be used for processing of data
      about complex biological objects modified by electron-dense labels.

PMID- 7819311
TI  - [Microcalorimetric study of the effect of mitoxantrone on chromatin DNA in vivo].
AB  - The influence of antitumor preparation--mitoxantrone on chromatin in tumor cell
      composition of BALB/c mouse spleen tissue was studied by the method of scanning
      microcalorimetry. It was shown that chromatin in normal cell composition
      denatured in two stages. The first stage--thermolabile domain is characterized by
      the transition parameters: T1d = 72, delta T1d = 6.2 degrees C, Qd = 36.5 J/g
      DNA, the second stage--thermostable domain: T2d = 83, delta T2d = 9.0 degrees C,
      Qd = 58 J/g DNA. The intraperitoneal injection of mitoxantrone to healthy mice
      slightly changes the structural parameters of chromatin but promotes the
      significant redistribution of heat between peaks, i.e. the part of
      heterochromatin fraction passes to euchromatin. In the case of leukemia,
      chromatin denatures in three stages with the following transition parameters: the
      first, the most thermolabile domain with T0d = 56.0, delta T0d = 5.0 degrees C,
      Qd = 20 J/g DNA; the second--thermolabile domain with T1d = 72.0, delta T1d = 6.2
      degrees C, Q1d = 16.5 J/g DNA; the third--thermostable domain with T2d = 83.0,
      delta T2d = 9.0 degrees C, Q2d = 58.0 J/g DNA. It is affirmed that the first
      stage is connected with melting of "naked" DNA regions in tumor chromatin
      composition. The injection of mitoxantrone to leukemic mice causes such changes
      in chromatin denaturation parameters that curve profile becomes similar to that
      of normal spleen tissue. We conclude that mitoxantrone causes transformation of
      spleen tumor cells into normal ones in vivo.

PMID- 7819312
TI  - [Analysis of geometric parameters and mechanical properties of erythrocytes by
      filtration through nuclear membrane filters. II. Experimental verification of a
      mathematical model].
AB  - In the accompanying paper the process of erythrocyte passage through pores of
      membrane nuclear filters has been modelled. In order to test the model we have
      studied how the filtration rate of human erythrocyte suspension depends on
      osmoticity of the resuspending medium at various experimental conditions. We have
      tested and verified the model conclusion that the zero filtration rate is reached
      at the critical osmoticity value which depends only on geometrical parameters of
      the pore and the cell and not on other properties of the erythrocyte. It has been
      demonstrated that the relative filtration rate only weakly depends on the
      hydrostatic pressure, in agreement with the model predictions. There is a good
      correspondence between the model and the experimental data about how the
      filtration rate is influenced by the viscosity of the intracellular content and
      the mechanical characteristics of the erythrocyte membrane at various
      temperatures.

PMID- 7819313
TI  - [Diffusion of glucose through the erythrocyte membrane].
AB  - The change of volume of human erythrocytes due to diffusion of glucose through
      their membranes was investigated. The dependence of membrane glucose penetration
      on functional state of the cells was discovered.

PMID- 7819314
TI  - [The effect of low intensity luminescent radiation on erythrocyte membranes].
AB  - It was found that luminescent monochromatized incoherent radiation causes
      inhibition of the ultraviolet light-induced hemolysis of erythrocytes comparable
      to that induced by laser light. The obtained data show reduction of the molecular
      product rate of free radical fat acyclic oxidation in the membranes of intact
      erythrocytes after irradiation by low intensity red light.

PMID- 7819315
TI  - [The possible functional role of the "spiral-helix" transition in the myosin rod
      in muscle contraction].
AB  - In Harrington's model, local helix-coil transition in coiled-coil portion of
      myosin is considered to be an origin of force generation in muscle. However, the
      detailed analysis of this model leads to the conclusion about the different
      functional role of the helix-coil transition in contracting muscle.

PMID- 7819316
TI  - [Photoinduced paramagnetic centers in human blood].

PMID- 7819317
TI  - [Surface activity of blood during hemosorption].
AB  - In the present work we investigate the surface-active property of blood in the
      process of hemosorption with help measuring of (tau-S)-curves of blood solutions.
      The blood's samples were taken on the entry and on the exit of sorption column on
      the 1-st, 20th and 30-th minutes after beginning of hemosorption. The all curves
      have point of bend and divided on the 4 line segments. With help of parameters of
      this segments we reconstruct isotherms and compare the blood isotherms of
      quantitatively. The parameters of segments can be differences for sure and this
      connected, apparently, with change of blood's plasma composition. The number of
      parameters were chosen on the (tau m-S)-isotherm. This is indicates so the stable
      of surface layer as the blood for this parameters.

PMID- 7819318
TI  - [Possible changes in blood vessels during exposure to electromagnetic field].
AB  - A mathematical model for changes in several typical blood vessels (aorta, artery,
      arteriole, capillary, venule, vein) under action of an alternating magnetic field
      (AMF) has been developed. It has been demonstrated that the blood serum ions
      interacting with the AMF have the largest impact in large vessels; changes in
      capillary parameters are small and can be caused mostly by neuronal factors and
      redistribution of the blood from in arteries and arterioles; the venous vessels
      are more susceptible the influence by the AMF as compared to the arterial ones.

PMID- 7819319
TI  - [X-ray diffraction study of adaptive changes in the structure of dense phase
      juice from the duodenum].
AB  - Low-angle X-ray diffraction patterns of canine duodenal juice precipitates taken
      at two stages of digestion, after 20 h fasting and after food stimulation have
      been obtained. Both diffraction patterns are due to glycoproteins. However, the
      glycoproteins contained in the precipitate after food stimulation occur in the
      native form while in fasting animals they are partially degraded.

PMID- 7819320
TI  - [Detection of nitric oxide formed from L-arginine in the murine stomach in vivo
      by EPR].
AB  - Suspension of baker's yeast loaded with a specific trap of nitric oxide (NO), a
      complex of Fe2+ with diethyldithiocarbamate (DETC), was used for the detection of
      NO formed in mouse stomach at its adaptive relaxation or under action of ethanol
      in vivo. NO formation was determined by the increase of intensity of the EPR
      signal due to mononitrosyl iron complex (MNIC) with DETC which appeared in yeast
      cells infused into the stomach. An increase of signal intensity was observed in
      stomach preparations isolated from mice when the doses of yeast suspensions
      injected p/o into mouse stomach for 40 min increased up to 1.5 ml or when 25%
      ethanol solutions were added p/o to the stomach. These effects were attenuated
      when NO-synthase inhibitor, NG-nitro-L-arginine was i/p injected into mice.

PMID- 7819321
TI  - [Analysis of the development of an epidemic during the spread of the leading
      variant of a pathogen. A mathematical model].
AB  - Study the possibility for realization of the biological principle of outstripping
      self-regulating interaction of parasite and host populations. The mathematical
      model of epidemic evolution process is applied to.

PMID- 7819322
TI  - [The carcinogen urethane induces high-amplitudes circaseptan variations in target
      tissues and disrupts the rhythm of cell count in lymphoid organs].
AB  - The presence of tumor is accompanied by biological rhythms disturbance both in
      damaged (target) organ, and in nondamaged systems. As discoordination of
      biorhythms is sometimes one of the causes of pathologic states, we have
      investigated, which changes in system of about 7-day duration (circaseptan)
      biorhythms preceded the tumor appearance. The model of lung carcinogenesis,
      induced by single dose (0.25 mg/g of body weight) of carcinogen urethan in A
      mice, was used. Characteristics of both target organ, and other organs was
      studied at the stage, preceding the tumor appearance. The data obtained were
      compared with the analogous characteristics of the control group, once injected
      with noncarcinogenic analog of urethan, methylcarbamate. The presence of about 7
      day rhythms in several organs, nonsensitive to carcinogenic action of urethan,
      was demonstrated in the control group. The periods of oscillations were: in bone
      marrow (the number of nuclear cells)--5.2 days; in thymus (mass; the number of
      nuclear cells)--7.8, 8.2 days; in liver (mass)--6.2 days; in kidney) mass)--8.9
      days; in blood (the number of leukocytes)--10.6 and 4.0 days, ect. In the control
      lungs low-amplitude rhythm of tissue mechanical characteristics (T = 3.5 days),
      was revealed (these characteristics indicate the extent to which cells are
      integrated into tissue). Single carcinogen injection resulted in statistically
      significant decrease (1.4-1.8 fold) of the periods of the main garmonic in the
      resistant organs. In lungs (target organ) powerful high-amplitude circaseptan
      oscillations, not inherent to the lungs of control mice, arise in this tissue
      after the carcinogen injection.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7819323
TI  - [The effect of polysaccharides on thermal denaturation of sarcoplasmic proteins
      from muscle homogenates].
AB  - When meat sarcoplasmic proteins interact with polysaccharides thermodynamic
      parameters of the systems are changed. The insoluble forms (natural plant matrix
      from wheat bran, cellulose) provide for partial denaturation of proteins at low
      temperatures (30-45 degrees C) and intensify subsequent coagulation processes. An
      increase of enthalpy with their increased concentration was found.
      Carboxymethylcellulose and pectin completely suppress protein coagulation,
      methylcellulose decreases enthalpy almost twice as compared to the solution
      without polysaccharides.

PMID- 7819324
TI  - The family of subtilisin/kexin like pro-protein and pro-hormone convertases:
      divergent or shared functions.
AB  - Six mammalian processing enzymes were recently discovered which exhibit
      significant similarities to both yeast kexin and bacterial subtilisins. These
      subtilisin/kexin-like convertases were called furin/PACE, PC1/PC3, PC2, PACE4,
      PC4 and PC5/PC6. The analysis of the mRNA expression of these convertases in rat
      tissues and cell lines by Northern blot analysis demonstrated a unique pattern
      for each enzyme. Thus, although furin and PACE4 mRNA (4.4 kb each) exhibit a
      widespread tissue distribution only furin is ubiquitously expressed. PACE4
      exhibits a major 4.4 kb mRNA form, and in some tissues a 3.9 kb form is detected.
      PC5 mRNA (3.8 kb major) is more restricted in its distribution than PACE4 and
      furin, and it exhibits the presence of multiple mRNA forms, resulting in variable
      lengths of the C-terminal Cys-rich domain. In addition, like furin and PACE4, PC5
      is expressed in both regulated and constitutively secreting cells. In contrast,
      PC1 (3 and 5 kb) and PC2 (2.8 and 5 kb) are primarily expressed in tissues and
      cells containing secretory granules. Multiple mRNA forms are also detected, but
      as far as is known none affect their open reading frame and only result in a
      variable length of the 3' non-coding sequence. Finally, PC4 mRNA (2.8 kb major
      and 1.9 kb minor) is only expressed in testicular germ cells. Biosynthetic
      analysis of the zymogen activation of PC1 and PC2 and their cleavage specificity
      following their cellular co-expression with a number of precursors, demonstrated
      that although pro-PC1 is rapidly activated to PC1 in the endoplasmic reticulum,
      pro-PC2 conversion into PC2 is rather slow. The cleavage of pro-PC2 into PC2
      starts in the trans Golgi network and is regulated by an endogenous endocrine and
      neural precursor called 7B2. Although the genetic organization of the convertase
      genes is very similar, they exhibit unique promoter sequences and only furin and
      PACE4 genes are localized on the same chromosome.

PMID- 7819325
TI  - Furin-mediated proprotein processing activity: involvement of negatively charged
      amino acid residues in the substrate binding region.
AB  - Furin, which is encoded by the recently discovered FUR gene, appears to be the
      first known mammalian member of the subtilisin family of serine proteases with
      cleavage selectivity for paired or multiple basic residues. A consensus cleavage
      sequence, Arg-X-Lys/Arg-Arg has been proposed. Most likely, furin is primarily
      involved in the processing of precursors of proteins that are secreted via the
      constitutive secretory pathway. Homology modelling of the catalytic domain of
      this protein suggested that negatively charged amino acid residues near or in the
      substrate binding region might contribute to the observed specificity for
      substrate segments with paired and multiple basic amino acid residues. To
      investigate this hypothesis, furin mutants were generated in which negatively
      charged residues, predicted to be located near or in the substrate binding
      pockets and involved in interactions with basic residues of the substrate, were
      replaced by neutral residues. Analysis of processing by these furin mutants of
      wild-type and cleavage mutants of pro-von Willebrand factor (pro-vWF) revealed
      that particular negatively charged residues are critical for specific cleavage
      activity.

PMID- 7819326
TI  - Processing of viral glycoproteins by the subtilisin-like endoprotease furin and
      its inhibition by specific peptidylchloroalkylketones.
AB  - The spike glycoproteins of many enveloped viruses are proteolytically cleaved at
      the carboxytermini of sequences containing the basic motif R-X-K/R-R. Cleavage is
      often necessary for the fusion capacity of the glycoproteins and, thus, for virus
      infectivity. Among these viruses are pathogenic avian influenza viruses, human
      parainfluenza virus, human cytomegalovirus, and human immunodeficiency virus; it
      has been demonstrated that these viruses can be activated by furin. Indigenous
      furin has been identified in T-lymphocytes, which are host cells for HIV. Furin
      has been localized in the TGN and on the surface of cells after vectorial
      expression. Peptidylchloroalkylketones have been designed that inhibit with high
      specificity cleavage and fusion activity of viral glycoproteins, as well as virus
      replication.

PMID- 7819327
TI  - Cleavage of prosomatostatins by the yeast Yap3 and Kex2 endoprotease.
AB  - A previous in vivo study implicated the YAP3 and KEX2 genes in the proteolytic
      maturation of anglerfish prosomatostatins which were heterologously expressed in
      the yeast Saccharomyces cerevisiae. In the present report, we have determined the
      cleavage specificity of these enzymes by incubating them in vitro with synthetic
      peptides mimicking the potential processing sites present in the somatostatin
      precursors and with full length prosomatostatin I. The Yap3 enzyme was prepared
      from a membrane fraction of a YAP3-overexpressing yeast, and a soluble form of
      Kex2 obtained from the culture medium of insect cells which had been infected
      with a recombinant baculovirus expressing the KEX2 gene. The identity of the
      cleavage products was confirmed by amino acid analysis. Our results show that
      both endoproteases generate mature SRIF-28 from prosomatostatin-II but that only
      Yap3 can process the homologous monobasic cleavage site (ie single arginine
      residue) found in prosomatostatin-I. Both enzymes were also shown to recognize
      the Arg-Lys doublet found in prosomatostatin-I producing a lysine-extended form
      of SRIF-14, which indicates that cleavage occurred C-terminal to the arginine
      residue. In addition, Kex2 also hydrolyzed C-terminal to the Pro-Arg motif to
      release a tripeptide-extended form of SRIF-14. However, neither endoprotease
      could cleave after the Arg-Lys doublet to release mature SRIF-14. Taken together,
      our results indicate that the yeast Kex2 and Yap3 endoproteases have distinct,
      though overlapping, substrate specificities. The results also strongly support
      the role of Yap3 as a proprotein convertase which perhaps defines a new family of
      processing enzymes.

PMID- 7819328
TI  - N-arginine dibasic convertase (NRD convertase): a newcomer to the family of
      processing endopeptidases. An overview.
AB  - N-arginine dibasic convertase (NRD convertase) (accession number L27124) is a
      metalloendopeptidase from rat brain cortex and testis which cleaves peptide
      substrates on the N-terminus of arginine residues in basic doublets. Its
      predicted amino acid sequence contains the putative zinc binding motif HXXEH in a
      region which exhibits 35% and 48% similarity with E coli protease III (pitrilysin
      E.C 3.4.99.44) and rat or human insulinase (E.C 3.4.99.45) respectively. This
      feature clearly classifies this endopeptidase as a member of the pitrilysin
      family of zinc-metalloproteases. However, the NRD convertase sequence contains a
      distinctive additional feature consisting of a 71 acidic amino acid stretch. Its
      substrate selectivity and the characteristic motifs of its amino acid sequence
      allow us to propose this new metalloendopeptidase as the first member of a new
      class of processing enzymes.

PMID- 7819329
TI  - Co-expression of PC2 and proenkephalin in human tumoral adrenal medullary
      tissues.
AB  - Expression of PC2, a Kex2-related protease, and of one of its possible
      substrates, proenkephalin, was examined in normal adrenal glands (n = 7) and
      pheochromocytomas (n = 20). PC2 could only be detected in normal adrenal glands
      using the sensitive RT/PCR technique. By Northern blot, PC2 and proenkephalin
      were expressed in 85% and 90% of the 20 pheochromocytomas studied, respectively.
      Moreover, in situ hybridization and immunohistochemistry confirmed expression of
      PC2 in human tumoral adrenal medullary tissue. These results show for the first
      time expression of PC2 in human pheochromocytomas which may be involved in the
      processing of proenkephalin.

PMID- 7819330
TI  - Regional distribution of neuropeptide processing endopeptidases in adult rat
      brain.
AB  - Many peptide hormone and neuropeptide precursors undergo post-translational
      processing at mono- and/or dibasic residues. An enzymatic activity capable of
      processing prodynorphin at a monobasic processing site designated 'dynorphin
      converting enzyme' has been previously reported in rat rain and bovine pituitary.
      In this study the distribution of dynorphin converting enzyme activity in ten
      regions of rat brain has been compared with the distribution of subtilisin-like
      processing enzymes and with the immuno-reactive dynorphin peptides. The
      distribution of dynorphin converting enzyme activity generally matches the
      distribution of immuno-reactive dynorphin B-13 in most but not all brain regions.
      The regions that are known to have a relatively large number of immuno-reactive
      dynorphin-neurons also contain high levels of dynorphin converting enzyme
      activity. The distribution of dynorphin converting enzyme activity does not match
      the distribution of subtilisin-like processing enzyme or carboxypeptidase E
      activities. Taken together the data support the possibility that the dynorphin
      converting enzyme is involved in the maturation of dynorphin, as well as other
      neuropeptides, and peptide hormones.

PMID- 7819331
TI  - T4-lymphocyte endoprotease responsible for the proteolytic processing of HIV-1
      gp160, like Kex2p endoprotease, is a calcium-dependent enzyme.
AB  - In the present study we show that precursor gp160 is cleaved in the HIV-1
      infected CEM (CD4+) cell line preferentially in the presence of calcium ions
      demonstrating that the responsible cellular endoprotease is a calcium-dependent
      enzyme. Taking into account this similarity, a synthetic peptide modelling the
      cleavage site of HIV-1 envelope glycoprotein precursor was used as substrate for
      Kex2p. Results obtained clearly showed that the processing enzyme Kex2p (EC
      3.4.21.61), a subtilisin-like serine protease that is encoded by the KEX2 gene of
      yeast Saccharomyces cerevisiae is able to cleave correctly this peptide at the
      potential cleavage site.

PMID- 7819332
TI  - Prohormone processing in permeabilized cells: endoproteolytic cleavage of
      prosomatostatin in the trans-Golgi network.
AB  - Many peptide hormones are synthesized as larger precursors which undergo
      endoproteolytic cleavage at paired basic residues to generate a bioactive
      molecule. Morphological evidence has implicated either the trans-Golgi network
      (TGN) or immature secretory granules as the site of prohormone cleavage. To
      identify the site where prohormone cleavage is initiated, we have used
      retrovirally infected rat anterior pituitary GH3 cells which express high levels
      of prosomatostatin, proSRIF, (Stoller TJ, Shields D (1988) J Cell Biol 107, 2087
      2095). By incubating these cells at 20 degrees C, a temperature that prevents
      exit from the Golgi apparatus, proSRIF accumulated quantitatively in the TGN and
      no proteolytic processing was evident. Following the 20 degrees C block, the
      cells were permeabilized and proSRIF processing determined. Cleavage of proSRIF
      to the mature hormone was approximately 35-50% efficient, required incubation at
      37 degrees C and ATP hydrolysis, but was independent of GTP or cytosol. The in
      vitro ATP-dependent proSRIF processing was inhibited by inclusion of chloroquine,
      a weak base, CCCP, a protonophore, or by pre-incubating the permeabilized cells
      with low concentrations of N-ethylmaleimide or bafilomycin, both inhibitors of
      vacuolar-type ATP-dependent proton pumps. These data suggest that ATP is required
      for generation of an acidic pH in the lumen of the TGN which is necessary for the
      activity of prohormone processing enzymes. By exploiting a permeabilized cell
      system, we have demonstrated that proSRIF cleavage is initiated in the TGN, in a
      reaction which is facilitated by a Golgi-associated vacuolar type ATPase.

PMID- 7819333
TI  - Identification of a sorting signal for the regulated secretory pathway at the N
      terminus of pro-opiomelanocortin.
AB  - The N-terminal 26 amino acids of the prohormone pro-opiomelanocortin (POMC) were
      investigated to determine whether this region has the capacity to act as a
      sorting signal for the regulated secretory pathway. Constructs were made using
      the N-terminal 101, 50, 26 or 10 amino acids of POMC fused to the chloramphenicol
      acetyltransferase (CAT) reporter protein and expressed in AtT20 cells to show
      that at least the first 26 amino acids were required to sort CAT to the regulated
      secretory pathway. Full length POMC was mutated by deleting amino acids 2-26 from
      the N-terminal region. Analysis of Neuro-2a cells expressing this mutation
      compared to wild type POMC indicated that these 26 amino acids contain
      information essential for sorting POMC to the regulated secretory pathway. The
      results presented here suggest the presence of a conformation-dependent signal in
      the N-terminal 26 amino acids of POMC responsible for sorting POMC to the
      regulated secretory pathway.

PMID- 7819334
TI  - Antibodies to secretogranin II reveal potential processing sites.
AB  - Several events occur during secretory granule maturation in endocrine and
      neuronal cells, one of the most important being the processing of prohormones. In
      addition, secretory granules undergo several changes during storage and
      maturation within the cell. We have been investigating the maturation of
      secretory granules in the neuroendocrine cell line PC12. Our working hypothesis
      postulates that fusion of newly budded secretory granules occurs during
      maturation and results in a larger secretory granule. We have been investigating
      the kinetics and specificity of the prohormone processing enzymes towards
      secretogranin II. Processing of secretogranin II must occur predominantly in the
      maturing secretory granule and could be used as a method to monitor secretory
      granule maturation.

PMID- 7819335
TI  - Peptides derived from the granins (chromogranins/secretogranins).
AB  - This review summarizes the role of granins (chromogranins/secretogranins) as
      precursors to biologically active peptides. We discuss the structural basis of
      the proteolytic processing of the granins, the consequences of their processing
      and the biological effects of granin-derived peptides.

PMID- 7819336
TI  - Post-secretory processing of regulatory peptides: the pancreatic polypeptide
      family as a model example.
AB  - Post-secretory metabolism is an important event in the overall homeostasis of
      regulatory peptides and the enzymes involved in these processes may be suitable
      targets for pharmacological intervention. Some examples are reviewed here.
      Peptide YY and neuropeptide Y, both members of the pancreatic polypeptide family,
      can be processed by dipeptidyl peptidase IV to their (3-36) fragments by removal
      of the N-terminal Tyr-Pro dipeptide, which generates a metabolite of different
      receptor selectivity. Aminopeptidase P and endopeptidase-24.11 also metabolize
      these peptides and the relative levels of these three cell-surface enzymes may
      regulate their interconversion between receptor-selective forms and inactive
      metabolites.

PMID- 7819337
TI  - The role of EC 3.4.24.15 in the post-secretory regulation of peptide signals.
AB  - In the present studies, we characterized the degradation of gonadotropin
      releasing hormone (GnRH) by tissues of the ovine hypothalamo-pituitary axis.
      Membrane and soluble fractions of the medial basal hypothalamus, the pre-optic
      area, the median eminence and the anterior pituitary demonstrated greater GnRH
      degrading activity than either hypophysial-portal or jugular plasma. The primary
      stable product of the membrane fractions was GnRH1-3, while the major product of
      the soluble fractions was GnRH1-5, both fragments were generated by plasma. Of
      all tissue fractions, the highest specific activity was observed in the soluble
      median eminence. Partial purification and characterization of soluble
      hypothalamic peptidase activity suggested that GnRH degradation by this tissue
      occurs via a two-step mechanism involving both post-proline cleaving enzyme and
      the metalloendopeptidase 3.4.24.15.

PMID- 7819338
TI  - Miniglucagon production from glucagon: an extracellular processing of a hormone
      used as a prohormone.
AB  - Glucagon is secondarily processed into its C-terminal (19-29) fragment, referred
      to as 'miniglucagon', which modulates the glucagon action. This extracellular
      processing, occurring at the level of of the glucagon target cells, is due to the
      presence at the cell surface of a new 100-kDa processing enzyme with
      characteristics of both thiol- and metalloprotease.

PMID- 7819339
TI  - Regulated cleavage of the Alzheimer amyloid precursor protein: molecular and
      cellular basis.
AB  - The relative utilization of alternative processing pathways for APP can be
      regulated by the activation state of certain protein phosphorylation signal
      transduction pathways. For example, activation of protein kinase C (PKC), or
      inactivation of protein phosphatases 1 and 2A, leads to a relative increase in
      utilization of the nonamyloidogenic, 'alpha-secretase' cleavage pathway for APP
      processing at the expense of other pathways. The molecular and cellular basis for
      this regulatory event is unknown. The possible mechanisms of regulated APP
      cleavage include (either singly or in combination): 1) substrate (ie APP)
      activation; 2) substrate redistribution; 3) enzyme (ie alpha-secretase)
      activation; or 4) enzyme redistribution. APP is a phosphoprotein; however, recent
      evidence from studies of the metabolism of mutant APP molecules suggests that
      changes in the APP cytoplasmic tail phosphorylation state may not be necessary
      for the phosphorylation-dependent activation of 'alpha-secretase' cleavage.
      Further, indirect immunofluorescent studies of the subcellular distribution of
      APP in the absence or presence of phorbol esters (PKC activators) fail to
      disclose obvious phorbol-induced redistribution of APP immunoreactivity. Taken
      together, current data suggest that major candidate phosphorylation-state
      sensitive targets relevant to the molecular basis of PKC-activated processing (or
      'regulated cleavage') of APP include the APP ectodomain as well as secretase
      enzymes and/or other components of the APP trafficking/processing apparatus.
      Progress in distinguishing among these possibilities is discussed.

PMID- 7819340
TI  - Identification and regulation of the high affinity binding site of the
      Alzheimer's disease amyloid protein precursor (APP) to glycosaminoglycans.
AB  - The specific binding of the amyloid protein precursor (APP) to glycosaminoglycans
      (GAG) suggests that APP is a cell adhesion molecule (CAM) and/or substrate
      adhesion molecule (SAM). In order to characterize this activity of APP in the
      brain at the molecular level, we have purified and characterized the major APP
      species from rat brain. The major isoform isolated was sequenced and found to be
      APP695. In a solid-phase binding assay, the specificity of this brain-specific
      APP isoform-GAG interaction was analysed. The binding of APP to the
      glycosaminoglycan heparin was found to be time-dependent and saturable. A strong
      heparin-binding site within a region conserved in rodent and human APP, APLP1 and
      APLP2, was identified. Saturable binding to heparin through this binding site was
      found to occur at nmol concentrations of APP. This putative high-affinity site
      was then located within a sequence of 22 amino acids in length corresponding to
      residues 316-337 of APP695. This sequence is encoded by APP exon 9 and the first
      three codons of exon 10. Since all APP and L-APP isoforms so far described
      include these exons, the strong heparin binding site is a ubiquitous feature of
      all APP and L-APP isoforms strongly suggesting that the brain-specific and
      neuronal, as well as the non-neuronal and peripheral APPs and L-APPs do have CAM-
      and SAM-like activities. Certain metal ions including zinc (II) have been
      proposed as risk factors in Alzheimer's disease (AD). Recently we showed that APP
      binds zinc (II) at higher nmol concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7819341
TI  - A recombinant form of angiotensin converting enzyme expressed from baculovirus
      infected insect cells.
AB  - A secreted form of the C-domain of angiotensin converting enzyme has been
      expressed from the baculovirus-infected insect cell system. This soluble enzyme
      was purified by affinity chromatography and characterised in terms of its
      carbohydrate side chains and binding of substrates and inhibitors.

PMID- 7819342
TI  - Heterologous biosynthesis and processing of preprovasopressin in Neuro2A
      neuroblastoma cells.
AB  - To obtain a model for the sorting and processing of preprovasopressin (preproVP),
      rat VP cDNA was transfected in murine Neuro2A neuroblastoma cells, which do not
      express VP. The precursor of VP was expressed and processed into the authentic VP
      gene products VP, neurophysin (NP) and glycopeptide (GP) as determined with
      reversed phase HPLC and radioimmunoassay. In addition, Neuro2A-specific forms of
      NP and GP were observed, which may be produced in the constitutive secretory
      pathway in these cells.

PMID- 7819343
TI  - Modulation of the biological activity of thyrotropin-releasing hormone by
      alternate processing of pro-TRH.
AB  - Thyrotropin-releasing hormone prohormone contains multiple copies of TRH linked
      together by connecting sequences. Like other plurifunctional prohormone proteins,
      pro-TRH undergoes differential proteolytic processing in various tissues to
      generate, beside authentic TRH, several other novel peptides corresponding to C
      terminally extended forms of TRH and connecting fragments. The pro-TRH connecting
      peptides are, together with TRH, predominant storage forms of TRH-precursor
      related peptides in the rat hypothalamus. Connecting peptides are co-localized
      with TRH in the median eminence nerve endings and co-released through a mechanism
      involving voltage-operated Ca2+ channels. The connecting peptide Ps4 is involved
      in potentiation of the action of TRH on thyrotropin hormone release by pituitary
      in vitro and in vivo through interactions with a specific pituitary cell receptor
      coupled to dihydropyridine and omega-connotoxin sensitive Ca2+ channels of the L
      type. It also causes dose-dependent increases in the steady state levels of mRNAs
      of TSH and prolactin through stimulation of the respective gene promoter
      activities. These findings indicate that Ps4 and TRH, two peptides which
      originate from a single multifunctional biosynthetic precursor, can function on
      the same target tissues in a coordinate manner to promote hormonal secretion.
      This suggests that differential processing of the TRH prohormone may have the
      potential to modulate the biological activities of TRH.

PMID- 7819344
TI  - Protein processing and morphogenesis of secretory granules in Paramecium.
AB  - The ciliated protozoan Paramecium provides a model system for the study of
      regulated secretion, featuring architecturally complex secretory storage granules
      trichocysts-docked at the plasma membrane, ready to respond to an exocytotic
      stimulus. The trichocysts are characterized by crystalline contents that confer
      upon the organelle a defined shape which can be altered by single gene mutation.
      The crystalline trichocyst contents are built up from a heterogeneous set of
      small acidic polypeptides generated by proteolytic maturation of a family of
      precursor molecules, suggesting an important role for protein processing in this
      system. We have recently shown that the primary defect in several secretory
      mutants lacking functional trichocysts is in intracellular trafficking rather
      than protein processing. However, analysis of how these defects lead to altered
      trichocyst shape supports the notion that the protein processing is essential for
      morphogenesis. Preliminary results of a cloning project reveal that an extensive
      multigene family (approximately 100 genes) codes for the trichocyst matrix
      proteins. Deduced amino acid sequences of putative processing sites indicate that
      (at least) two distinct processing reactions are probably involved in the
      maturation of these proteins, and allow us to speculate that each reaction may
      control a key event of trichocyst biogenesis.

PMID- 7819345
TI  - Expression of the carboxypeptidase E gene: characterization of the initiator
      binding proteins.
AB  - Several of the genes for enzymes involved in peptide hormone processing, such as
      carboxypeptidase E (CPE), do not contain a TATA box. The region surrounding the
      major transcription initiation site of the CPE gene has sequence homology with
      the 'initiator' (Inr) elements of the TATA-less terminal
      deoxynucleotidyltransferase (TdT) gene, and the adenovirus major late (AdML) and
      other promoters. To investigate the promoter region of the CPE gene, GH4C1 cells
      were transiently transfected with constructs containing the luciferase reporter
      gene attached to various portions of the rat CPE gene (-395 to +45). Positive
      regulator elements were detected in positions -84 to -12 and +30 to +47. However,
      the Inr-like element of the CPE gene (-12 to +20) produced detectable luciferase
      activity in the absence of upstream and downstream sequences. This region of the
      CPE gene was much more active when expressed in the normal (sense) orientation
      than when expressed in the antisense orientation. A mutation within the consensus
      sequence between CPE and other Inr elements was much less active than the wild
      type sequence. Interestingly, deletion of the Inr and surrounding sequences
      produced a large increase in the transcription from upstream sites, suggesting
      that proteins which bind at, or near, the Inr sequence suppress transcription
      from other sites. To characterize GH4C1 nuclear proteins which bind to the CPE
      gene, Southwestern blotting, UV cross-linking, and gel shift analyses were
      performed. The Southwestern analysis showed that the CPE and AdML Inr sequences
      labeled several proteins of similar sizes which are distinct from the
      transcription factor USF; this factor has been previously reported to bind to the
      AdML Inr sequence. A CPE Inr-binding protein co-purifies with an AdML Inr-binding
      protein on a CPE Inr affinity column. Gel shift assays showed that with some
      binding conditions, the proteins that bind to the CPE sequence also bind to the
      TdT and AdML Inr elements. Taken together, these results indicate that the -12 to
      +20 region of the CPE gene has the properties of an Inr element which binds some,
      but not all, of the factors which bind to other Inr elements.

PMID- 7819346
TI  - AIDS and the adolescent.
AB  - Recent findings on young people's response to HIV/AIDS and its perceived
      relevance to their sexual lives are reviewed. Research into adolescent sexual
      behaviour suggests a trend, over the last 2 decades, for an earlier age of first
      intercourse and a greater number of recent and lifetime sexual partners. Older
      cohorts of adolescents and those with either multiple partners or more 'steady'
      partners have been found to have lower rates of condom use. Data on the
      prevalence of specific sexual activities such as anal intercourse, while sparse,
      suggests a considerable number of young people engaging in behaviours carrying
      some risk of HIV infection. It is clear that sex education programmes which
      simply advocate 'safer sex' practices without addressing the interpersonal skills
      and emotional implications of negotiating such practices, and which do not
      provide a positive view of sexual health, are failing to influence adolescent
      behaviour. Recent research has highlighted a number of issues that need
      addressing if sex education and HIV/AIDS prevention campaigns are to be
      effective.

PMID- 7819347
TI  - Cerebrospinal fluid proteins in neurosyphilis and HIV infection.
AB  - This paper briefly reviews the factors which influence the concentrations of
      proteins, particularly immunoglobulins, within the CSF and how antibodies which
      are locally synthesized within the central nervous system can be detected by the
      laboratory. The use of nitrocellulose immunoblotting for the identification of
      antibodies which are specific to Treponema pallidum and Human Immunodeficiency
      Virus Type-1 are discussed.

PMID- 7819349
TI  - Attitudes towards and experience of general practice among HIV-positive patients
      in the Republic of Ireland.
AB  - In order to study their attitudes to and experience of general practitioner care,
      150 attenders at the only HIV specialist clinic in the Republic of Ireland were
      asked to complete an anonymous, self administered questionnaire. (81%) of
      respondents reported having a regular GP and 94% of those indicated that the GP
      was aware of their HIV diagnosis. The majority (64%) of patients with a regular
      GP reported seeing their doctor on more than 5 occasions during the previous
      year. Most patients were satisfied with the support which they received from
      their GPs. Even so, the majority of patients (72%) would go directly to the
      hospital clinic for any problem which they perceive to be HIV related.

PMID- 7819348
TI  - GPs, STDs and life insurance.
AB  - We sought to ascertain general practitioners' (GPs) views on their patients'
      attendances at genitourinary medicine (GUM) departments regarding methods of
      referral, record keeping and supplying of information to insurance companies. A
      questionnaire was sent to 429 local GPs of whom 294 (68%) responded. A written
      means of referral was less likely for HIV than for sexually transmitted disease
      (STD) (P < 0.001), and in turn less likely for STD than for other genital
      problems (P < 0.02). The percentage of GPs who did not keep a record of referrals
      were: For HIV testing--29%; STDs--13%; and for other genital problems--8%. Whilst
      48% of GPs did not feel obliged to divulge lifestyle information on a patient,
      21% would feel it necessary to confirm that a patient had suffered from an STD if
      the 'source' on a cytology smear was shown to be that of a GUM department. Only
      23 GPs (8%) felt they had sufficient knowledge as to the use to which the
      information they supplied to insurance companies was put. Many GPs acknowledged
      that their practice, with reference to patient attendance at a GUM department,
      was influenced by life insurance considerations. Bearing in mind the current
      policy of The Association of British Insurers which recommends that all
      applicants for life insurance be asked to declare any previous STD and
      counselling/testing for HIV, we make several suggestions which may aid GPs in
      this difficult area.

PMID- 7819350
TI  - Seroprevalence and incidence of sexually transmitted diseases in a rural Ugandan
      population.
AB  - The aim of the study was to determine in a rural population the age- and sex
      specific prevalence and incidence rates of serological reactivity of 5 common
      sexually transmitted diseases (STDs) and their association with HIV-1 antibody
      status. Of the adult population of two villages (529 adults aged 15 years or
      more) 294 provided an adequate blood specimen both on enrollment and at 12
      months. The sera were tested at 3 collaborating laboratories for antibodies
      against HIV-1, Treponema pallidum, Haemophilus ducreyi, Chlamydia trachomatis and
      herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2). A sample of 45 children
      were tested for HSV-1 and HSV-2. Seroprevalence rates in adults on enrollment
      were 7.8% for HIV-1, 10.8% for active syphilis, 10.4% for H. ducreyi, 66.0% for
      C. trachomatis, 91.2% for HSV-1 and 67.9% for HSV-2. Males were significantly
      more likely than females to be seropositive for H. ducreyi (15.6% versus 6.6%),
      but less likely to be HSV-2 antibody positive (57.0% versus 74.4%). Reactivity to
      H. ducreyi, C. trachomatis and HSV-2 rose with increasing age. In contrast,
      active syphilis showed no age trend. All STDs tended to be more common in those
      HIV-1 seropositive. Incidence rates over the 12 months were nil for HIV-1, 0.5%
      for syphilis, 1.2% for H. ducreyi, 11.3% for C. trachomatis, and 16.7% for HSV-2.
      The results of this exploratory study indicate that all STDs included are common
      in this rural population. The high HSV-2 prevalence rate among adolescents
      suggests that HSV-2 may be an important risk factor for HIV-1 infection.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7819351
TI  - Abdominal pain in women attending a genitourinary medicine clinic: who has PID?
AB  - Eighty-one women who presented to a genitourinary medicine clinic with mild to
      moderate acute or chronic abdominal pain were studied in order to compare the
      clinical features of those who had pelvic inflammatory disease (PID) and those
      who did not. The diagnosis was made by laparoscopy, and PID was detected in 14%,
      adhesions in 11% and endometriosis in 16%. Women with PID were clinically
      indistinguishable from women with other diagnoses or no obvious cause.

PMID- 7819352
TI  - The role of early colposcopy in the management of females with first episode
      anogenital warts.
AB  - 212 females attending a genitourinary medicine (GUM) clinic with first episode
      anogenital warts were screened by cervical cytology and colposcopy/histology for
      the presence of cervical epithelial abnormalities in keeping with infection by
      the human papillomavirus (HPV infection) and/or cervical intraepithelial
      neoplasia (CIN). The prevalence of cervical epithelial abnormalities detected by
      cervical cytology alone was 32%, rising to 56% after colposcopic examination.
      However, the majority of cervical lesions detected by colposcopy alone were of
      low grade (HPV infection and/or CIN I). Histologically-confirmed high grade
      cervical lesions (CIN II or CIN III) were detected more frequently in those
      females in whom cervical cytological examination indicated dyskaryosis in keeping
      with any grade of CIN, compared to females without dyskaryotic changes on
      cervical smear (P < 0.05, chi-squared test with Yates' correction). Early
      colposcopy is indicated for females with anogenital warts in the presence of a
      cervical smear showing dyskaryosis in keeping with any grade of CIN, because of
      the statistically significant increased risk of detecting a potentially
      progressive high grade cervical lesion. In females without dyskaryotic changes on
      cervical smear, the value of early colposcopy is uncertain and warrants larger
      more long-term trials.

PMID- 7819353
TI  - Sexual behaviour among London GUM clinic attenders: implications for HIV
      education.
AB  - The aim of this study was to describe the sexual behaviour of a sample of
      genitourinary medicine (GUM) clinic attenders, 5 years after the launch of the UK
      government HIV media campaigns. A gender-specific and anonymous cross-sectional
      self-completion questionnaire was modified from the National Survey of Sexual
      Attitudes and Lifestyle and completed by 250 men and 250 women. The majority of
      the respondents were in their twenties, lived in London and were employed or
      students. Sixty-eight per cent of the men reported that one or more of their last
      3 partners was not a regular partner. For those men whose last sexual encounter
      was with a new partner, 27% of heterosexuals and 33% of homosexuals reported
      using a condom. Fifty-one per cent of women reported one or more non-regular
      partners among their last 3 partners. For those women whose last sexual encounter
      was with a new partner, 43% of heterosexuals and 75% of bisexuals used a condom.
      Seventy-eight per cent of men and 75% of women had had a previous sexually
      transmitted disease (STD). These findings highlight the persistence of practices
      associated with the risk of contracting or transmitting HIV infection and which
      needs to be addressed in future educational campaigns. The GUM clinic population
      is an important population to monitor over time, either by longitudinal or serial
      cross-sectional studies. The results of this study provide a baseline against
      which to gauge the effects of future educational interventions.

PMID- 7819354
TI  - The use of intravenous pentamidine as prophylaxis against Pneumocystis carinii
      pneumonia in patients with HIV infection.
AB  - The purpose of this study is to report on the use of monthly intravenous
      pentamidine as prophylaxis against Pneumocystis carinii pneumonia (PCP) within a
      central London HIV unit. A retrospective case note analysis of HIV-seropositive
      individuals using intravenous pentamidine as PCP prophylaxis was carried out.
      Aspects examined included reasons for using the regimen, compliance, adverse
      reactions and episodes of PCP. Eight patients were studied. There was no
      prophylaxis failure in 5 patients. Three patients developed PCP whilst on the
      regimen, although their compliance was poor. In patients who are intolerant of
      established prophylaxis regimens, intravenous pentamidine may be a useful
      alternative. It is well tolerated, although compliance is the main problem.
      Further prospective studies are indicated to assess its efficacy.

PMID- 7819355
TI  - Sampling for vaginal candidosis: how good is it?
AB  - In defined patient populations attending a genitourinary medicine department,
      screening for vaginal candidosis resulted in 26.3% positive rate. Microscopy
      using Gram-stained slide was useful in early diagnosis and resulted in the
      detection of 64.8% of symptomatic cases. Samples from the anterior fornix proved
      most sensitive for culture diagnosis while the left lateral vaginal wall proved
      least sensitive (positive predictive value 0.88 cf 0.81).

PMID- 7819356
TI  - High prevalence of herpes simplex virus type 1 in female anogenital herpes
      simplex in Newcastle upon Tyne 1983-92.
AB  - This retrospective study was undertaken to evaluate the prevalence of the viral
      types and temporal epidemiology in patients with ano-genital herpes between 1983
      92. One thousand one hundred and thirty-five patients with anogenital herpes were
      available for analysis. The annual incidence of anogenital herpes nearly tripled
      over the period of 7 years (1986-92) from 59 to 171 cases. The percentage of HSV
      1 infection in female cases (63-79%) was much higher than in other reported
      studies and remained relatively constant over the study period.

PMID- 7819357
TI  - Comparison of the influence of spermicidal and non-spermicidal contraception on
      bacterial vaginosis, candidal infection and inflammation of the vagina--a
      preliminary study.
AB  - This preliminary study compared the signs, symptoms and prevalence of bacterial
      vaginosis (BV) and candidal infections in women using spermicides, with those
      using other forms of contraception, to establish whether nonoxynol-9 had any
      therapeutic value against BV or gave rise to vaginal candidiasis and
      inflammation. Overall results showed that the prevalence of BV in non-spermicide
      users was 35/113 (31%) but was significantly less in spermicide users, 10/66
      (15%), P < 0.05. Nonoxynol-9 was not associated with increased isolation of
      Candida albicans, which was found in 16/113 (14%) of non-spermicide users, and in
      8/66 (12%) of those using spermicides, P > 0.1. Vaginal inflammation and
      discharge were significantly less in spermicide users, 19/66 (29%) than in the
      non-spermicide group, 50/113 (44%), P < 0.05. Nonoxynol-9 contraception was
      associated with a significantly reduced prevalence of BV, but not with increased
      candidiasis or vaginal inflammation.

PMID- 7819358
TI  - Risk behaviours for HIV infection and sexually transmitted diseases among female
      sex workers from Copenhagen.
AB  - In 1990-91, 237 female sex workers from Copenhagen were enrolled in a larger
      study performed in 9 European countries. None of 206 women accepting serological
      testing was HIV-infected despite the fact that 36 (17.5%) were injecting drug
      users (IDU). Whereas 95% of the women always used condoms with clients over the
      last 6 months, this proportion was 25% and 9% respectively for casual and regular
      non-paying partners (P < 0.0001 for both comparisons). Those reporting at least
      one STD over the last year had more non-paying sexual partners than the others (P
      < 0.01) and the frequency of STD was lower in women who always used condoms with
      non-paying partners (7% vs 31%, P = 0.01). Women working on the street were more
      often IDU than others (78% vs 7%, P < 0.001). Independently of drug use, street
      prostitutes also tended to have more clients (P = 0.007) and more STD (P = 0.05).
      The striking differences in condom use with clients as compared to non-paying
      partners and the association between STD and sexual behaviours with such partners
      but not with clients show that specific interventions should be designed to
      promote safer sex with non-paying partners.

PMID- 7819360
TI  - An audit of safer sexual practice and knowledge in patients attending a
      genitourinary medicine department.

PMID- 7819359
TI  - Female genital schistosomiasis as a risk-factor for the transmission of HIV.
AB  - Sexually transmitted diseases increase the probability for HIV transmission,
      presumably through lesions in the genital mucosa. Female genital schistosomiasis,
      a special form of urinary schistosomiasis due to infection with Schistosoma
      haematobium, may be another risk-factor for transmission of HIV. From published
      data there seem to be pathophysiological, immunological and epidemiological
      evidence for an association between genital ulcer disease due to S. haematobium
      and HIV-infection in women. Female genital schistosomiasis could be seen as an
      example of how an interaction between a parasitic disease and HIV facilitates the
      propagation of the latter. As long as the prevalence of HIV is low in the general
      population, interventions targeted to high risk groups will significantly delay,
      or even prevent, widespread dissemination of the HIV infection in the rest of the
      population. If female genital schistosomiasis is a risk factor for the spread of
      HIV like other genital ulcer diseases, there should be interesting ways to
      intervene from the public health point of view.

PMID- 7819361
TI  - Audit of patients' knowledge of their oral contraceptive pill.

PMID- 7819362
TI  - Audit evaluating the value of routine screening of Chlamydia trachomatis urethral
      infections in men.

PMID- 7819363
TI  - Surveillance of sexual behaviour and patients' reasons for requesting HIV tests.

PMID- 7819364
TI  - Time off work and financial implications of genitourinary medicine clinic
      attendance.

PMID- 7819366
TI  - Gonorrhoea in homosexual and bisexual men.

PMID- 7819365
TI  - A survey of Thai sexual behaviour and risk of HIV infection.

PMID- 7819367
TI  - Cervical epithelial abnormalities in females with and without genital warts.

PMID- 7819368
TI  - The prevalence of urogenital Chlamydia trachomatis infection in a refugee
      community in El Salvador.

PMID- 7819369
TI  - Graft-induced recovery of inhibitory avoidance conditioning in striatal lesioned
      rats is related to choline acetyltransferase activity.
AB  - Four groups of male Wistar rats showing disrupted inhibitory avoidance
      conditioning due to striatal lesions received either striatal or ventral
      mesencephalic brain grafts. Two additional non-lesioned groups were used as
      controls. Half of the groups was retrained in an inhibitory avoidance task at
      fifteen days postgraft and the other half at sixty days postgraft. Those animals
      receiving striatal grafts significantly improved their ability to acquire the
      inhibitory avoidance task at fifteen and sixty days postgraft, as opposed to
      those receiving mesencephalic grafts, which did not show behavioral recovery.
      Choline acetyltransferase and glutamate decarboxylase activities, as well as
      dopamine content, were measured in the grafted tissue. Striatal grafts showed
      levels of choline acetyltransferase activity similar to the control group.
      Moreover, a positive correlation was found between the choline acetyltransferase
      activity and the behavioral recovery. In contrast, both glutamate decarboxylase
      activity and dopamine levels were significantly lower in striatal and in
      mesencephalic grafts, as compared to the controls. These results show that
      striatal but not mesencephalic grafts can promote the restoration of the ability
      to acquire an inhibitory avoidance task even at early stages (15 days) of the
      development of the grafts. The results also suggest that acetylcholine plays an
      important role in behavioral recovery.

PMID- 7819370
TI  - Ultrastructural circuitry in retinal cell transplants to rat retina.
AB  - The development of five transplants of fetal retinal tissue to adult rat eyes was
      examined with the electron microscope. The transplants were of 9 to 10 weeks
      total age after conception in four cases and 20 weeks in one case. They were at
      stage E15 when transplanted. Transplants developed in both the epiretinal and
      subretinal spaces. The transplants were heterogeneously developed with some parts
      showing almost normal differentiation and others little. Subretinal transplants
      examined in this study were more developed than epiretinal grafts. Photoreceptor
      cells developed both inner and outer segments. Their synaptic terminals possessed
      output ribbon synapses with postsynaptic processes similar to those seen in
      normal retinas. In regions corresponding to the inner plexiform layer, the adult
      complement of synapses was seen, including advanced features such as serial
      synapses as well as reciprocal synapses at bipolar cell dyads. Incompletely
      differentiated synapses of both the amacrine and bipolar cell types were often
      observed, especially in the rat epiretinal transplants. Ganglion cell processes
      could not be identified with certainty. Although transplant cells were adjacent
      to host photoreceptor cells and pigment epithelium, obvious specializations or
      interactions were not observed. The experiments suggest that embryonic rat
      retinal cell transplants develop most or perhaps all of the structural components
      and neuronal circuitry necessary to transduce light and process some visual
      information.

PMID- 7819371
TI  - Origin of afferent projections into bovine chromaffin cell implants in the rat
      periaqueductal gray determined by retrograde and anterograde tracing.
AB  - We have previously described long-term survival of isolated bovine chromaffin
      cell suspension grafts in the periaqueductal gray of adult rats. Electron
      microscopic analysis of the graft sites revealed synapses on the transplanted
      chromaffin cells. The origin of these synapses is not known, but they are
      probably derived from the host since the initial grafts were suspensions of
      chromaffin cells that were essentially free of other cell types. In order to
      determine the origin of the observed synapses, retrograde and anterograde tracer
      analyses were performed on grafted rats at 4 and 8 weeks after transplantation.
      Following injection of the retrograde tracer (Fluoro-Gold) into graft sites, four
      major host sites were labeled: hindbrain reticular formation, substantia nigra,
      lateral hypothalamus, and cingulate cortex. Injection of anterograde tracer
      (rhodamine-conjugated dextranamine) into the substantia nigra, lateral
      hypothalamus, and cingulate cortex produced labeled fibers and terminals in and
      around 4 and 8 weeks old chromaffin cell graft sites. An increase in both the
      number of retrogradely labeled cells, as well as in the density of anterogradely
      labeled fibers and terminals within the graft site, was observed from 4 to 8
      weeks. This study shows that graft innervation from the host is primarily from
      areas that normally project afferent fibers to the periaqueductal gray. The
      increase in labeled fibers and terminals over 8 weeks suggests that de novo
      synapse formation on grafted bovine chromaffin cells is a continuous process that
      is dependent on the regenerative capacity and plasticity of the host neuronal
      network and the grafted bovine chromaffin cells.

PMID- 7819372
TI  - Optimization of adrenal medullary allograft conditions for pain alleviation.
AB  - Previous findings in our laboratory have demonstrated that transplants of adrenal
      medullary tissue into the spinal subarachnoid space can alleviate pain, most
      likely via sustained local release of pain-reducing neuroactive substances from
      the transplanted chromaffin cells. The success of this work in animal models has
      led to preliminary clinical trials with promising results. However, before large
      scale clinical studies are undertaken, numerous issues should be resolved, many
      of which can be readily addressed initially in the laboratory. One of these is
      the amount of donor adrenal medullary tissue necessary to produce long-term
      antinociception. Although tissue from two adrenal glands has generally been used,
      it is unknown whether less would be equally effective, or more could increase
      analgesic potency. To address this, various amounts of adrenal medullary tissue,
      ranging from one to ten donor glands, were used. Results showed lowered
      antinociceptive benefits when only one adrenal medulla was used, but only small
      and short-lived increases when donor material was increased substantially. In
      addition, assays of catecholamine and Met-enkephalin release in the host spinal
      CSF revealed only slight further increases following the transplantation of more
      than 2-4 glands. These results indicate that a small amount of adrenal medullary
      tissue is necessary and sufficient to produce sustained antinociception, and
      suggest that higher amounts may result in tolerance development or feedback
      inhibition. Another important issue is the ability to retain antinociceptive
      potency if donor tissue is maintained in culture prior to transplantation, since
      the coordination of donor harvesting and recipient availability is often
      difficult. To address this, donor adrenal medullary tissue was maintained in
      explant culture for various periods following dissection. Results indicated that
      adrenal medullary tissue can be maintained in culture for up to 30 days prior to
      transplantation without decrement in antinociceptive potency, and that a period
      of 7-21 days results in improved graft viability. Results of this study indicate
      that some of the critical issues for successful neural transplantation outcomes
      can be initially addressed in pre-clinical studies.

PMID- 7819374
TI  - Analysis of felodipine by packed column supercritical fluid chromatography with
      electron capture and ultraviolet absorbance detection.
AB  - A reproducible and selective supercritical fluid chromatography (SFC) method was
      developed for the analysis of felodipine, a drug indicated for the treatment of
      hypertension. Methanol-modified carbon dioxide was employed as the SFC mobile
      phase with both electron capture detection (ECD) and multi-wavelength detection
      (MWD) being used simultaneously for analyte determination. Chromatography limit
      of detection (LOD) and limit of quantitation (LOQ), linear dynamic range (LDR)
      and injection precision were obtained in order to assess chromatographic and
      detector performance for both the SFC/MWD and SFC/ECD/MWD systems. The method was
      shown to be stability indicating since felodipine could be separated from its
      potential oxidative degradation product, H152/37, in under 6 min (felodipine k' =
      2.44). Sample throughput was increased by 60% with the SFC assay vs LC. The
      optimized SFC method was shown to be equivalent to an existing LC/UV procedure
      for the analysis of a sustained-release tablet while realizing a 92% saving in
      disposable solvent waste. In order to achieve further solvent savings overall,
      supercritical fluid extraction (SFE) with 8% methanol-modified carbon dioxide as
      the extraction fluid was used to extract felodipine from a sustained-release
      tablet (as opposed to traditional solvent extraction). Comparable drug recoveries
      were obtained with SFE sample preparation technique when either SFC or LC extract
      analysis was utilized.

PMID- 7819373
TI  - Effects of intraventricular locus coeruleus transplants on seizure severity in
      genetically epilepsy-prone rats following depletion of brain norepinephrine.
AB  - Audiogenic seizures (AGS) in genetically epilepsy-prone rats (GEPR) of the
      moderate-seizure substrain (GEPR-3s) were investigated to determine whether
      norepinephrine (NE) depletion induced by 6-hydroxydopamine (6-OHDA) microinfusion
      into the locus coeruleus (LC) could alter the efficacy of intraventricular NE
      tissue grafts in promoting reductions in seizure severity in AGS. GEPR-3s were
      stereotaxically infused with 6-OHDA (4 micrograms/side/rat), or vehicle into the
      region of the LC. Following 6-OHDA treatment all animals were subjected to 3 AGS
      tests. GEPR-3s seizure severities were increased in 39.5% of the animals after
      microinfusion of 6-OHDA into the region of the LC. Following the third AGS test,
      each rat was stereotaxically implanted with 17 gestational day rat fetal tissue
      obtained from the dorsal pons and containing the primordia of the LC or with
      tissue obtained from the neocortex or were sham-grafted. Subsequent to grafting,
      rats were subjected to 3 additional AGS tests. 53% (10/19) of 6-OHDA treated
      GEPRs showed a significant reduction in seizure severity following
      transplantation of fetal LC tissue. In contrast, only 20% (1/5) of GEPRs infused
      with saline rather than 6-OHDA showed a reduction of seizure severity following
      fetal LC transplantation. NE content in the cortex and pons/medulla was decreased
      by 78% and 46% respectively following 6-OHDA microinfusion into the LC. Prominent
      grafts with numerous TH positive neurons and neurites were present within the
      third ventricle of grafted animals, while cortex grafts contained no TH
      immunostained structures. These findings suggest that the efficacy of fetal LC
      tissue to promote reductions in seizure severity in GEPRs is increased following
      depletion of central NE by microinfusion of 6-OHDA.

PMID- 7819375
TI  - Binding constant determination of WIN 22169, a novel polymeric ligand.
AB  - WIN 22169 is a co-polymer containing approximately 11 repeating units of
      polyoxyethylene and diethylenetriamine pentaacetic acid (DTPA). WIN 66368, a
      magnetic resonance imaging (MRI) contrast agent, is the gadolinium III complex of
      WIN 22169. WIN 22169 has been characterized with respect to its equivalent
      weight, acidity constants and excess acid or base, as well as its metal ion
      binding constants. The logs of the equilibrium binding constants of the ligand to
      Gd3+, Ca2+, Zn2+ and Cu2+ were found to be 16.6, 7.47, 12.2 and 14.0. The Gd
      selectivity constant, a measure of the preferential binding of the ligand toward
      Gd3+ versus the three in vivo ions: Ca2+, Zn2+ and Cu2+, of WIN 66368 was
      calculated to be 7.9. This value compares favourably to that for Gd DTPA which
      has a Gd selectivity constant of 7.04.

PMID- 7819377
TI  - Probing the conformation of protein (bFGF) precipitates by fluorescence
      spectroscopy.
AB  - Aggregation and precipitation are major events in the handling and aging of most
      protein pharmaceuticals. We demonstrate the utility of fluorescence spectroscopy
      in determining protein conformation in precipitates using basic fibroblast growth
      factor (bFGF) as an example. Conversion of the native to the soluble denatured
      from by chaotropes was accompanied by an increase in tryptophan emission. The
      emission spectra of resuspended precipitates were as reproducible as the spectra
      of the soluble form. The sum of emission spectra of native soluble bFGF and
      denatured precipitated bFGF was superimposable on the spectrum of the
      unfractionated suspension, suggesting that quantitative analysis of denatured
      aggregates in turbid protein formulations is possible. The ratio of tryptophan to
      tyrosine emissions increased with increasing extent of denaturation both in
      solution and in suspension. For example, salting out by ammonium sulphate
      increased the fluorescence index (indicative of denaturation) which was
      reversible upon dissolution. In addition, aging (35 degrees C) of bFGF in the
      presence of sulphated ligands produced precipitates with native-like fluorescence
      index, in contrast to denatured precipitates formed without ligands.

PMID- 7819376
TI  - Analysis of enloplatin by liquid chromatography and of platinum by atomic
      absorption spectrometry in various biological fluids.
AB  - Analytical methods were developed and validated for the determination of
      enloplatin (an anticancer agent) in plasma by reversed-phase LC and for platinum
      (an elemental component of enloplatin) in plasma, plasma ultrafiltrate (PUF) and
      whole blood by flameless atomic absorption spectrometry (FAAS). The LC procedure
      involved protein precipitation with dilute perchloric acid. The supernatant was
      mixed with sodium phosphate buffer and injected into the LC system. A C18 or a
      cyano column was used, depending on sample matrix, with UV detection at 230 nm.
      The LC method was linear from 0.50 to 50.0 micrograms ml-1. Inter-day and intra
      day precision (RSD%) and accuracy (relative error%) were < +/- 14%. The FAAS
      procedure utilized a graphite furnace, a hollow cathode platinum (Pt) lamp, and
      Zeeman background correction. An aliquot of plasma, PUF, or whole blood was mixed
      with a solution of Triton X-100 and Antifoam-B and injected into the FAAS system.
      The FAAS method showed goodness of fit from 0.05 to 10.0 micrograms Pt/ml. Inter
      day and intra-day precision and accuracy were < +/- 15%. The methods were
      developed to support pharmacokinetic studies in humans, dogs and rats.

PMID- 7819378
TI  - Crystallinity, hygroscopicity and dissolution of moricizine hydrochloride
      hemihydrate.
AB  - A typical anhydrous moricizine hydrochloride, an antiarrhythmic agent, is a non
      hygroscopic crystalline material. Three lots of moricizine hydrochloride were
      found to deliquesce within a day at 85% relative humidity, exhibit different X
      ray powder diffraction (XRPD) patterns and have more rapid dissolution rate than
      that of typical anhydrous material. No change in XRPD pattern was observed when
      the solvent (ethanol) was removed from these lots by heating to 80 degrees C. A
      two-step water release was observed by thermogravimetric analysis (TGA): a
      surface water release and a water of hydration release, for these heated samples.
      The stoichiometry of the water of hydration suggests that it is a hemihydrate.
      The dissolution rate of the hemihydrate was faster than that of typical anhydrous
      material. This hemihydrate could be converted to a typical anhydrous material by
      heating to 90 degrees C. The granules obtained by a simulated wet granulation
      process on typical lots and typical lots containing up to 20% of hemihydrate
      exhibited similar physical behaviour to that of typical anhydrous material.

PMID- 7819379
TI  - Determination of MK-383, a non-peptide fibrinogen receptor antagonist, in human
      plasma and urine by radioimmunoassay.
AB  - MK-383 is a novel, non-peptide fibrinogen receptor antagonist. A sensitive and
      specific radioimmunoassay has been developed for the determination of this drug
      candidate in plasma and urine. The immunogen was prepared by coupling to albumin
      via the N-hydroxysuccinimide ester from which the radioligand was also prepared
      by reaction with [I125]iodotyrosine. The method was specific and no
      immunoreactive material other than the parent drug was detectable in plasma and
      urine from dosed volunteers. This direct assay, using 5 microliters of plasma or
      0.5 microliter of urine, is sensitive to 1 and 10 ng ml-1, respectively, without
      matrix interference and has sufficient sensitivity, specificity, accuracy, and
      precision for the analysis of clinical samples.

PMID- 7819380
TI  - Determination of linopirdine and its N-oxide metabolites in rat plasma by liquid
      chromatography.

PMID- 7819381
TI  - A rapid method for the separation and analysis of leaked and liposomal entrapped
      phosphoramide mustard in plasma.
AB  - Pharmacokinetic studies of liposomal drugs should include simultaneous
      determination of leaked and entrapped drug in biological specimens. Due to the
      limited stability of many liposomal preparations in biological samples, a rapid
      analytical procedure is often necessary. Phosphoramide mustard (PM), a key
      cytotoxic metabolite of a widely used alkylating drug cyclophosphamide, has
      recently been entrapped into a liposomal formulation and the preparation has been
      found to be rather unstable in plasma. We have, therefore, developed a rapid
      method for the separation of liposome-associated PM from the unassociated drug
      and a method for their quantitation in plasma. This method involves the use of
      size exclusion mini-gel column and requires minutes to process. Due to the use of
      internal standards, this method tolerates low recovery and requires the
      collection of a single fraction of each of liposome-associated PM and the
      unassociated drug. The recovery of liposomal PM from the first fraction of the
      gel column was found to be 82.4 +/- 7.9% (SD, n = 8), whereas that of liposome
      unassociated PM from the major fraction was 16.8 +/- 2.8% (SD, n = 8). However,
      the low recovery problem of liposome-unassociated PM was circumvented by adding
      the internal standard [alpha, beta-2H8] PM prior to separation, thus compensating
      for the loss of liposome-unassociated PM due to incomplete collection. Two types
      of standard curve were constructed for quantitation of liposome-associated PM and
      unassociated PM and the linearity for both was excellent. Assay validation
      indicated that within-run RSD values at 213 ng, 426 ng and 1065 ng for liposomal
      PM were 4.2, 4.3 and 3.0%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7819382
TI  - Ethanol unfolds firefly luciferase while competitive inhibitors antagonize
      unfolding: DSC and FTIR analyses.
AB  - Firefly luciferase has gained popularity as a protein model in elucidating
      anaesthesia mechanism because the bioluminescence of the purified enzyme system
      is extremely sensitive to volatile anaesthetics. This study analysed the thermal
      unfolding of firefly luciferase by differential scanning calorimetry (DSC) and
      Fourier transform infrared spectroscopy (FTIR). DSC showed that the transition of
      firefly luciferase from the folded (N) to unfolded (D) state occurred at 41.7
      degrees C with the excess heat flow of 1.6 cal g-1 protein. Ethanol decreased the
      transition temperature dose dependently. In contrast, luciferin competitors,
      anilinonaphthalenesulphonate (ANS), toluidinonaphthalenesulphonate (TNS), and
      myristic acid increased the transition temperature. The competitive inhibitors
      antagonized unfolding and stabilized the N-state. Ethanol promoted unfolding and
      stabilized the D-state. Temperature scan by FTIR agreed with the DSC data. The
      intensities of amide-I' and amide-II' bands started to increase at 20-25 degrees
      C. This temperature coincides with the temperature where the bioluminescence of
      firefly luciferase is maximal. The unfolding effect of ethanol was evident even
      at 5 degrees C. ANS, TNS, and myristic acid completely protected the enzyme from
      the thermal unfolding. This is the first demonstration that the noncompetitive
      inhibitors induce the isothermal first-order phase transition in a functional
      protein, whereas competitive inhibitors protect the enzyme from thermal
      unfolding. The action mode of competitive inhibitors on firefly luciferase is
      completely different from that of noncompetitive inhibitors.

PMID- 7819383
TI  - Liquid chromatography determination of liposome components using a light
      scattering evaporative detector.
AB  - Analysis of liposomal components is important in stability testing of
      formulations. An LC method for the analysis of liposomal components cholesterol,
      phosphatidylcholine, phosphatidylglycerol, phosphatidylethanolamine and their
      lyso-forms was developed. The method uses a light-scattering evaporative detector
      and isocratic mobile phase. In addition, components of pH-sensitive liposomes,
      cholesterylhemisuccinate and cationic lipid dimethyldioctadecylammonium bromide
      used in transfections were determined by the method. The separations were carried
      out on a Spherisorb S5 NH2 cartridge column or Zorbax NH2 column (25 cm x 4.6 mm,
      5 microns particle size). The mobile phase consisted of acetonitrile-methanol
      ammonium acetate solution (pH 4.8, 0.1 M) (52:32:16, v/v/v) at a flow rate of 2
      ml min-1. Detection limits were 1.3-8.0 micrograms ml-1 depending on the lipid.
      The precision (RSD) of the method was 1.5-3.3% for lipid standard solutions at 50
      micrograms ml-1 concentration and 2.0-11.8% for lipids analyzed from liposome
      suspensions.

PMID- 7819384
TI  - Determination of bisphosphonate drugs in pharmaceutical dosage formulations by
      ion chromatography with indirect UV detection.
AB  - Application of ion chromatography (IC) to the analysis of non-chromophoric
      bisphosphonate drugs in pharmaceutical dosage formulations is described. The
      method is based on the use of single-column ion chromatography in conjunction
      with indirect UV detection that obviates the need for tedious chemical
      derivatization procedures. Diluted drug samples are chromatographed directly on a
      Waters IC-Pak HR anion-exchange column with dilute nitric acid (1.6-12 mM) as the
      mobile phase which exhibits a UV absorption maximum near 220 nm. Analyte
      detection is monitored by measuring the decrease in absorption of the mobile
      phase. The IC method has been validated and shown to be precise, accurate,
      specific and rugged for routine assay. Application of the method to the
      determination of alendronate sodium tablets, etidronate disodium injectable
      (which requires an eluent pH control for chromatographic resolution of active
      drug from chloride ions) and clodronate disodium injectable is presented. The
      performances of the Waters IC-Pak HR and several equivalent columns are also
      discussed.

PMID- 7819385
TI  - Automated analytical systems for drug development studies. I--A system for the
      determination of drug stability.
AB  - An automated system consisting of a pH-stat, microdialysis sampling and a liquid
      chromatograph was assembled to measure the rate of rapid chemical reactions.
      2',3',5'-Triacetyl-6-azauridine was used as a model compound to validate the
      performance of the automated system. Buffer catalysis was minimized by using a
      non-catalytic concentration of borate buffer along with a pH-stat to maintain the
      pH during the kinetic run. The microdialysis sampling technique permitted sample
      quenching and buffering of the solutions to a pH compatible with the LC column
      materials. The combination of microdialysis sampling and rapid LC analysis
      allowed reactions with a half-life of approximately 1 min to be sampled every 30
      s. The rates of hydrolysis of the drug, measured at different conditions of
      temperature (37-70 degrees C) and pH (9.0-10.5) using the automated system,
      compared well with the previously determined values.

PMID- 7819386
TI  - [Chemical modification of myoglobin by isothiocyanate reagents. The effect of
      modifying the N-terminal amino group on protein conformation].
AB  - Sperm whale met-Mb was chemically modified by fluorescein isothiocyanate (FITC)
      and methylisothiocyanate (MITC) at pH 6.5-7.0. Individual met-Mb derivatives,
      FITC-Mb and MITC-Mb, modified at the alpha-NH2-group of Val I (NAI), were
      obtained by ion exchange chromatography with 10 and 30% yields, respectively, and
      characterised. The His 12 (AI0) residue was found to be additionally
      thiocarbamylated in MITC-Mb. Large amounts of the remaining intact met-Mb (more
      than 50%) were isolated in both cases alongside with small fractions of the
      deeper modified protein. The absorption and CD spectra of met-Mb, FITC-Mb and
      MITC-Mb in the UV and visible spectral regions, the spectrophotometric titration
      curves in the Soret band and tryptophanyl fluorescence of the apo- and
      holomyoglobins in the pH range of 2-13 were investigated. It is shown that
      modification of the N-end had no influence on the conformation (alpha-helicity)
      of the polypeptide chain of Mb but caused specific changes in the absorption and
      CD spectra, pK values of met-hydroxy transition, and the pH-dependent
      fluorescence of the modified species as compared to the native met-Mb. The data
      obtained evidence in favour of both the changed local conformation of the N
      terminal region and the heme environments in FITC-Mb and MITC-Mb.

PMID- 7819388
TI  - [Thermoreactive hydrogels in biotechnology and medicine].
AB  - The properties of thermoreactive hydrogels (TH), i.e., hydrogels formed by
      polymers which exhibit a lower critical solution temperature (LCST) behaviour in
      aqueous solutions, are discussed. TH shrink drastically and lose water on heating
      at temperatures close to LCST resulting in gel collapse. This process is
      reversible, and TH swell again to their initial size. TH can be successfully used
      for concentrating suspensions and protein solutions, for immobilization of
      biocatalysts, in drug delivery systems and in biosensors.

PMID- 7819387
TI  - [A stable conformer of IgG, prepared by an acidic influence: study by
      calorimetry, binding of the C1q complement component, and monospecific anti-IgG].
AB  - Thermal stability and functional activity of rabbit IgG in its native
      conformation and after incubation at pH 2.0 were studied using differential
      scanning calorimetry and binding of conformational probes, i.e., the C1q
      component of the complement and two monospecific anti-IgG antibodies. The latter
      reacted selectively with the "hinge" region joining the Fab and Fc fragments of
      IgG or with the CH2 domain in the Fc fragment. At pH 2.0 complete unfolding of
      rabbit IgG did not occur: the protein demonstrated the presence of secondary and
      compact tertiary structures but differed from the native conformation by
      decreased overall enthalpy and TM of thermal denaturation as well as by changed
      secondary structure parameters as could be evidenced from CD spectroscopy and
      scanning calorimetry data. Incubation at pH 2.0 followed by renaturation at
      neutral pH led to irreversible conformational changes in IgG. The most
      significant differences between the two IgG conformers were demonstrated by
      calorimetry at pH 3.5 which revealed that the acid-treated conformer differs from
      the native one by enhanced thermal stability of the CH2 domain. Using the
      combination of thermodynamic and functional studies, it was shown that the origin
      of stabilization was the increase in the extent of interaction between the CH2
      domain in the Fc fragment and the CHI domain in the Fab fragment. This resulted
      in the increase of the functional link between the antigen-binding domain and the
      C1q binding site in the CH2 domain of the acid-induced IgG conformer. In parallel
      with the increase in stability of the CH2 domain, conformational changes in the
      "hinge" region were found, together with the absence of intrinsic conformational
      changes in the CH2 domain proper as could be judged from C1q and monospecific
      anti-IgG binding assays. The results obtained demonstrate one of possible
      mechanisms whereby functionally significant rearrangements in the IgG molecule
      can be induced by changes in the interactions between invariably folded domains
      rather than by intrinsic changes in the domain conformation.

PMID- 7819389
TI  - [Binding of secreted protein mRNA translation products with artificial
      phospholipid vesicles].
AB  - Translocation of eucaryotic secretory proteins across the phospholipid membrane
      containing no protein components has been studied. The level of translocation was
      found to depend critically on the physico-chemical properties of the membranes.
      It was found also that eucaryotic secretory proteins can pass through the
      phospholipid bilayer by both co- and post-translational interactions.

PMID- 7819390
TI  - [Modification of biochemical changes in developing cultures of chick embryo nerve
      tissue cultures].
AB  - The effects of exogenous ganglioside GM1 (1 microM) from bovine brain on the
      morphological state and biochemical parameters (creatine kinase,
      acetylcholinesterase and adenylate cyclase activities as well as the protein,
      phospholipid and ganglioside content) have been studied in primary cultures of
      trypsin-treated dissociated cells of chicken embryonic brain. Ganglioside GM1
      accelerated the growth and differentiation of cultured cells, increased the
      phospho- and glycolipid content and stimulated the activity of the enzymes.

PMID- 7819391
TI  - [Interaction of native 5'-ATP with rat liver cell membranes and adipose tissue].
AB  - Studies have been carried out to evaluate specific binding and enzymatic
      hydrolysis of native 5'-ATP by rat liver and adipose tissue plasma membranes.
      Addition of [14C]ATP to membranes resulted in sequential nucleotide hydrolysis
      occurring via stepwise enzymatic reactions: ATP-->ADP-->AMP-->adenosine, thus
      indicating a high ecto-phosphatase activity of the plasma membranes under study.
      The ATP-binding kinetic characteristics were studied using a high-speed
      filtration technique under complete inhibition of membrane nucleotidases by
      excess EDTA (40 mM). Comparative analysis of [3H]ATP displacement by other
      nucleotides (ADP, AMP, GTP, GMP) revealed that only ADP was in equimolar
      competition with ATP for its binding sites. Adenosine and beta-glycerophosphate
      did not exert any significant effect on [3H]ATP binding to the membranes.
      Graphical representation of [3H]ATP binding data in a Scatchard plot showed a
      linear dependence, indicating the existence of a single ATP-binding site with Kd
      about 50-60 nM and Bmax of 5-7 pmol/mg protein. It is suggested that these sites
      represent a nucleotide-binding component of P2 purine receptors and are tightly
      coupled with the catalytic site of membrane ecto-ATPase.

PMID- 7819392
TI  - [Study of physiological functions of human ceruloplasmin. The effect of
      ceruloplasmin on immunocytes in a normal state and in pathology].
AB  - The immunomodulating effect of ceruloplasmin (CP) on the major components of the
      immunocompetent system of the organism--the natural resistance system and the
      specific immune response--has been established. CP can exert various influences
      on the level of expression of specific markers of T- and B-lymphocytes (as
      determined by various modifications of the rosette-forming test), on the
      phagocytic activity of neutrophils and monocytes as well as on the activity of
      "respiratory burst" enzymes. CP modulation was found to depend predominantly on
      the initial level of the immunological parameters to be determined, i. e., on the
      extent of immune inflammation in human patients. Thus, it was found that CP not
      only plays the roles of an antioxidant and a copper-transporting protein, but is
      also capable to interact with immunocytes, altering their biological activities.
      The observed immunotropicity of CP, its ability to directly interact with
      immunocytes and to model the immune function at the cell level provides evidence
      for the existence of a universal molecular language of information exchange
      between the macroorganism cells of various nature and origin.

PMID- 7819393
TI  - [ANSA analysis. I. Mixtures of substrates in analyzing proteases: features of the
      kinetics of hydrolysis during competition].
AB  - Studies designed to investigate the utility of mixtures of chromogenic peptide
      substrates for protease analysis are reviewed. Individual applications of
      aminonaphthalenesulfonamide substrates with a variable structure of the leaving
      group are discussed. The kinetic curves describing the mixtures of competing
      substrates are presented and the conditions of the occurrence of S-shaped curves
      specified. The kinetic differences for mixtures of competing substrates split by
      a single enzyme and for those independently split by various substrates are
      demonstrated. A comparison between experimental and calculated kinetic curves is
      made. The cause of erratic results obtained in a number of studies using
      substrate mixtures is indicated.

PMID- 7819394
TI  - [ANSA analysis. II. Aminonaphthalenesulfonamides--detecting groups for
      polysubstrate analysis of proteases].
AB  - The properties and synthetic methods of aminonaphthalenesulfonamides (ANSA) used
      as detectable groups of protease substrates are described. A list of chemical and
      physical properties of seventeen 5.1-ANSA with simple substituents is presented.
      A comparison of condition for the introduction and removal of acyl protecting
      groups (acetyl, trifluoroacetyl, phthaloyl, carbobenzoxy) used in ANSA synthesis
      is given. Examples of applicability of nitronaphthalenesulfonamides as
      intermediate compounds are given. The possibility of ANSA alkylation at both N(C)
      and N(S) is demonstrated. Substituted ANSA--sulfonylaziridenes--are used for the
      production of water-soluble derivatives containing the alcoxy group in the
      sulfonamide fragment. Criteria for the selection of detectable groups for
      polysubstrate analysis are discussed. Eighteen typical procedures for ANSA
      synthesis according to the schemes discussed are presented.

PMID- 7819395
TI  - [ANSA analysis. III. Synthesis of aminonaphthalinesulfonamide chromogenic
      substrates for protease analysis].
AB  - A review of synthetic methods of peptide substrates containing
      aminonaphthalenesulphonamide (ANSA) as the detected leaving group is presented.
      Variations of aminoacylic and peptide ANSA derivatives using ANSA as the C
      protect group at all stages of the peptide synthesis, condensations of the ANSA
      with the N-protected peptide fragment obtained preliminary, the application of
      aminoacyl-ANSA as syntones are discussed. The synthesis scheme used while
      determining optimal ANSA substrates that involves reactions of aminoacyl
      derivatives of aminonaphthalenesulfonylchlorides with amines is shown. The
      application of di-tert-butylpyrocarbonate, DCC, chlorodimethylformiminium
      chloride, alkylchloroformate as condensing agents is described. The protection of
      amino groups was carried out by using Boc- and Cbz- groups.

PMID- 7819396
TI  - [ANSA analysis. IV. Specificity spectra in characterizing proteases and mixtures
      of them].
AB  - ANSA-analysis was used for characterization of proteases and their mixtures, such
      as snake venoms. The method is based on the cleavage by proteases of mixtures of
      competing chromogenic substrates containing substituted
      aminonaphtalenesulfonamide (ANSA) detectable groups. All detectable ANSA groups
      in the substrate mixtures have non-identical modifiers, one or two substituents
      in the sulfonamide fragment and can be determined by chromatographic methods. To
      identify venoms, a mixture of six peptide substrates cleaved at the Arg-ANSA bond
      was proposed. Hydrolysis of this substrate mixture catalyzed by the venoms of
      different Crotalidae and Viperidae species gave characteristic chromatograms
      (ANSA spectra) for each tested sample. A method for quantitative description of
      differences in ANSA spectra has been proposed. Each ANSA spectrum can be
      presented as a vector going from the origin of the coordinated axes to a point in
      an n-dimensional space (n is the number of assayed ANSA products of proteolysis)
      with peak squares of corresponding ANSA as coordinates. The similarity between
      two ANSA spectra will then be characterized by angle between their vectors.

PMID- 7819397
TI  - [ANSA analysis. V. Secondary specificity of peptidases to the structure of
      detected groups of aminonaphthalenesulfamide chromogenic substrates].
AB  - Mixtures of competing aminonaphthalenesulfonamide (ANSA) substrates can be used
      for identifying secondary substrate specificity of peptidases and their mixtures.
      All substrates in the mixture had identical amino acid residues; however, cleaved
      ANSA differed in chromatographic mobilities due to differences in the substituent
      in the sulfonamide residue. ANSA generated by limited proteolysis of the
      substrate mixture by the enzyme preparation were detected chromatographically.
      The chromatogram obtained (the ANSA spectrum) was characteristic of each enzyme
      or enzyme-containing preparation. Using arginyl-ANSA mixtures, informative ANSA
      spectra suitable for enzyme identification were obtained. The correlations
      between the structure of the substituents in the SONR1R2 group of ANSA and the
      efficiency of substrate hydrolysis were studied. The method was used to identify
      snake venoms.

PMID- 7819398
TI  - [ANSA analysis. VI. Activation, inhibition and interaction of proteases in enzyme
      mixtures].
AB  - A new accurate method (ANSA-analysis) is used for studying the interactions of
      proteases with their inhibitors or other proteases. The method is based on the
      cleavage by proteases of mixtures of competing chromogenic substrates containing
      aminonaphthalenesulfonamide (ANSA) detectable groups. Each substrate contained a
      specifically substituted ANSA group which showed its specific retention time
      during chromatographic separation. For the analysis of blood coagulation,
      mixtures of blood-clotting factor substrates were used. Hydrolysis of the
      substrate mixture catalyzed by blood samples gave characteristic chromatograms
      (ANSA spectra) for each sample. The activation time before injection of the blood
      sample into the substrate mixture and the pool of clotting factors and inhibitors
      both had influence upon the ANSA spectrum. The ANSA spectra of mixtures of
      trypsin and/or chymotrypsin with snake venoms are described as A x (the ANSA
      spectrum of a protease) + B x (the ANSA spectrum of a venom) + C x (the ANSA
      spectrum of catalytically active interaction products). They are additive (A = B
      = 1, C = 0), if no proteolysis, inhibition or activation takes place. ANSA
      spectra analysis shows deviations from additivity for some mixtures of Viperidae,
      (including E. carinatus), Naja naja, Agkistrodon contortrix and A. halys venoms.
      Explanations for the inability to detect inhibitors in venoms having a high
      protease activity by previously used methods are given.

PMID- 7819400
TI  - [The role of thyroid hormones in regulating the activity of phospholipases A1 and
      A2 in liver cells and nuclei from rats of varying ages].
AB  - The activity of phospholipases A1 and A2 in liver cells and liver cell nuclei of
      rats of various age and the thyroid status of experimental animals have been
      studied. It was found that phospholipid deacylation and acylation in liver cells
      is under control of thyroid hormones. Age-specific fluctuations in the activity
      of the thyroid gland may be one of possible reasons for phospholipase A1 activity
      and phospholipid level changes in liver nuclei during ontogenesis. Thyroid
      hormones play an important role in regulation of polyunsaturated fatty acid
      metabolism and prostaglandin E2 production in the liver.

PMID- 7819399
TI  - [Closure of Ca2+-dependent pores by cyclosporin A: the role of magnesium ions,
      adenine nucleotides, and conformation status of the ADP/ATP antiporter].
AB  - Effects of ADP and Mg2+ on the ability of cyclosporin A to "reseal" mitochondria
      permeabilized by Ca2+ and P(i) have been studied. Cyclosporin A was completely
      ineffective, when ADP and Mg2+ were not included into the incubation medium. Both
      ADP and Mg2+ used at high concentrations potentiated the effect of cyclosporin A
      and prevented it reversal by carboxyatractylate. Data on the influence of
      different concentrations of ADP and Mg2+ on the resealing efficiency of
      cyclosporin A suggest that the true effector modulating the state of the Ca(2+)
      dependent pore is the ADP-Mg2+ complex, but not ADP or Mg2+ used separately. The
      ability of non-hydrolyzable analogs of adenine nucleotides, ADP-S and ATP-S, to
      potentiate the resealing action of cyclosporin on mitochondria permeabilized by
      loading of different Ca2+ concentrations to that of ADP was compared. ATP-S was
      ineffective when the pore was induced by high concentrations of Ca2+. The results
      obtained are discussed in terms of hypothesis on the direct involvement of the
      ADP/ATP antiporter in regulation of the inner mitochondrial membrane Ca(2+)
      dependent pore state.

PMID- 7819401
TI  - [Mechanism of ovalbumin proteolysis].
AB  - Papain, thermitase and pepsin at pH 4.0 hydrolyze ovalbumin to low molecular
      weight peptides. Simultaneously a stepwise formation of several short fragments
      resulting in the appearance of a group of high molecular weight fragments and a
      subsequent splitting of the latter into two fragments of intermediate molecular
      mass takes place. The fragments are retained in the molecule by noncovalent
      bonds. The fragments formed under the action of different enzymes are similar in
      size, which is suggestive of splitting in the same narrow segments of the
      ovalbumin polypeptide chain. The results obtained indicate that during
      proteolysis of the native ovalbumin two extreme types of the proteolysis--the one
      by-one and zipper types--occur in parallel, while the course of the latter is
      largely determined by the ovalbumin structure.

PMID- 7819402
TI  - [Structure-activity characteristics of cytochrome P-450c21. Immunochemical
      approaches and limited proteolysis].
AB  - To elucidate the general principles of the structural organization and
      functioning among mitochondrial and microsomal steroidogenic cytochromes P-450, a
      comparative study of the molecular organization of microsomal cytochrome P-450c21
      and mitochondrial cytochrome P-450scc from adrenal cortex has been performed
      using immunochemical approaches and limited proteolysis. An efficient method to
      isolate and purify cytochrome P-450c21 has developed and the antibodies against
      the hemoprotein raised and characterized. Limited trypsinolysis of cytochrome P
      450c21 leads to the formation of two fragments tightly bound to the microsomal
      membrane. Proteolytic modification is accompanied by spectral changes and the
      decreases of the catalytic activity. Possible models of the molecular
      organization of cytochrome P-450c21 are discussed in comparison with
      mitochondrial cytochrome P-450scc and liver microsomal cytochrome P-450.

PMID- 7819403
TI  - [Influence of ceruloplasmin on the embryotoxic effect of silver ions].
AB  - The effect of alimentary administration of silver salts upon embryogenesis in
      rats has been studied. Feeding of AgCl to pregnant female rats throughout
      gestation did not result in any alterations in their physiological functions,
      although the active copper-containing ceruloplasmin (Cp) was eliminated from the
      blood stream. However, anomalous development of embryos, their prenatal death or
      total mortality of newborn rats within the first 24 hours after birth were
      evidenced. The copper content in the placenta and embryonic tissues decreased
      appreciably. The Cu,Zn-superoxide dismutase (SOD) activity was diminished in the
      cytoplasm of embryonic cells alongside with its drop, though less pronounced, in
      the tissues of the pregnant females. The embryotoxicity of AgCl was considerably
      reduced by repetitive injections of native Cp to pregnant rats. Such treatment
      caused an increase in the SOD activity in the placenta and embryonic tissues.
      Mortality of the newborns also went down. It is suggested that the embryotoxic
      effect of AgCl is due to its ability to interfere with copper metabolism, by
      altering the copper-transporting function of Cp.

PMID- 7819404
TI  - [Uncoupling of the liver monooxygenase system by perfluorocarbons in vivo].
AB  - Administration of a perfluorodecalin (PFD) emulsion, the liver cytochrome P-450
      II B1/B2 inducer, to experimental animals is followed by a two-fold increase of
      the NADPH oxidation rate in liver microsomes. This phenomenon is caused by the
      presence in the cytochrome P-450 active center of PFD which uncouples microsomal
      hydroxylation. The high rate of NADPH oxidation in liver microsomes after
      administration of the fluorocarbon does not decrease the level of reduced
      pyridine nucleotides in the liver and does not change the glucose concentration
      in the plasma. It is suggested that the accelerated weight loss in starved
      animals following PFD administration is due to the energy dissipation in the
      fluorocarbon uncoupled monooxygenase reactions in the liver.

PMID- 7819405
TI  - [Study of DNA-protein crosslinks induced by UV light in Hela cells].
AB  - UV-Irradiation (lambda = 254 nm) of Hela cells in the monolayer causes a dose
      dependent formation of DNA-protein crosslinks (DPC). The time-dependent protein
      increase unaccompanied by a change in the complex yield was observed for the
      fraction of the DNA-protein complex passing into the aqueous phase by phenol
      extraction, when the cells were transferred to a fresh culture medium after UV
      irradiation. These data suggest that DPC do not repair, while DNA or the protein
      within the complex can firmly bind additional quantity of protein during the post
      irradiation period.

PMID- 7819406
TI  - [Interaction of formaldehyde with nucleic acids and their structural components
      in the presence of amines. V. Isotopic exchange of hydrogen 3H---1H at the C8
      atom of dATP, adenosine, adenine, guanosine, and poly(A)].
AB  - It has been shown that the effect on [8-3H]dATP, [8-3H]A and [8-3H]poly(A) of the
      formaldehyde mixture with the primary aliphatic amine carrying an amino group at
      the chain terminus (glycine, its methyl and ethyl esters, tripeptide Gly-Gly-Gly,
      taurine, ethanolamine, methylamine, ethylamine), under conditions close to
      physiological ones (pH 5.5-9, 40-50 degrees), initiates a fast reaction of
      isotope H2 exchange: 3H-->1H at the C-8 atom of the adenine residue. Substitution
      of the primary amine for a secondary one decreases the rate of hydrogen exchange
      by more than two orders of magnitude. Under the effect of the formaldehyde
      mixture with Gly or Sar on guanosine or of the HCHO-Sar mixture on adenosine, the
      hydrogen exchange at the C-8 atom of the both nucleotides proceeds at the same
      rate. The mechanism of fast hydrogen exchange at the C-8 atom of 9-substituted
      adenines under conditions of the Mannich reaction via the N6,N7-cycloderivative
      (III) is discussed.

PMID- 7819407
TI  - [Determination of homoserine kinase activity by chromatographic separation and
      measurement of reaction products].
AB  - A highly specific procedure for quantitative assay of the homoserine kinase
      activity in an optimized enzymatic reaction using 14C-labelled homoserine or
      [gamma 33P]-ATP as substrates, and paper or thin-layer chromatography for
      separation of the formed o-phosphohomoserine, is described. The procedure is
      simple, sensitive and allows the assay for the activity of both purified and non
      purified homoserine kinases.

PMID- 7819408
TI  - [Co-oxidation of phenols and 4-aminoantipyrene catalyzed by microperoxidase and
      their complexes with proteins].
AB  - The kinetic parameters of 4-aminoantipyrine (AAP) co-oxidation with phenol or p
      iodophenol in a wide range of hydrogen peroxide concentrations were compared for
      microperoxidases MP-8, MP-9, MP-11, horseradish peroxidase (HRP) and peroxidase
      of Arthromyces ramosus (PAR). The peroxidatic activity increased in the following
      order: HRP > PAR > MP-9 > MP-8 > MP-11. Microperoxidase complexes with human
      serum albumin (1:1) retained their peroxidatic activity at high H2O2
      concentrations, protecting haem from destruction by active radicals. Monoclonal
      antibodies against porphyrin decreased the peroxidatic activities of three
      microperoxidases during co-oxidation of AAP and phenol and protected haem. Inert
      proteins (BSA, ovalbumin) had little effect on the HRP activity, whereas enzyme
      specific antibodies strongly activated HRP at high concentrations of hydrogen
      peroxide, thereby forming an immune complex protecting HRP from its dissociation
      down to haem and the apoenzyme.

PMID- 7819409
TI  - [The role of the 3'-CCA sequence in the interaction of tRNA(Phe) from E. coli and
      Thermus thermophilus with homologous phenylalanyl-tRNA-synthetases].
AB  - The 3'-CCA end of tRNA(Phe) from E. coli and Thermus thermophilus was modified by
      stepwise degradation and ligation of the shortened tRNA with different
      trinucleotides (pUpUpA, (pA)3, (pC)3, (pU)3). Kinetic parameters for the
      aminoacylation reaction of modified tRNAs have been determined. The role of the
      3'-terminal trinucleotide of tRNA(Phe) in tRNA binding and aminoacylation by
      phenylalanyl-tRNA synthetases from E. coli and Thermus thermophilus is
      postulated.

PMID- 7819410
TI  - [Regulation of biosynthesis of molecular forms of ceruloplasmin in rat
      ontogenesis].
AB  - Ceruloplasmin (CP) expression at the level of formation of its molecular forms in
      the liver and other rat organs during ontogenesis has been studied. The synthesis
      of CP commenced on day 15th of embryogenesis and coincided in time with the
      completion of formation of the fetal liver. This period of rat embryo development
      was marked by the appearance of two molecular forms of newly formed CP, one of
      which was secreted in vitro by isolated fetal liver, while the other one was
      found in the membrane fraction of extrahepatic embryonic tissues. The proportion
      of CP among the total protein of these fractions increased up to term,
      correlating with the gain in the embryo weight. The relative content of CP
      secreted by the livers of newborn animals remained constant up to day 9th of
      postnatal life and then increased with the age up to approximately 1.5 months. At
      the same time, the serum concentration of CP remained constant up to day 19th of
      postnatal life. The increased rate of secreted CP synthesis in the liver during
      ontogenesis coincided with the appearance of a newly formed non-secreted membrane
      bound form of CP in hepatocytes. The ontogenetic dynamics of synthesis of various
      molecular forms of CP in the liver correlated with the results of immunoblotting
      of CP polypeptides in Golgi membranes isolated from the livers and the livers and
      the liver of a 30-day-old rat.

PMID- 7819411
TI  - ["Classical" apo B,E-receptor does not mediate the activating effect of low
      density lipoproteins on the second messenger system in human platelets and
      vascular smooth muscle cells].
AB  - The possible role of the "classical" LDL receptor (apo B,E-receptor) in
      activation of second messenger systems in human platelets and vascular smooth
      muscle cells (VSMC) has been investigated. The LDL-induced elevation of free
      cytoplasmic Ca2+ in platelets and VSMC was not inhibited by EGTA, which is known
      to block the LDL interaction with the apo B,E-receptor. Heparin abolished the
      binding of LDL to the apo B,E-receptor but did not influence the LDL-induced
      accumulation of inositol phosphates in VSMC. Acetylation or carbamylation of
      lysine residues, or modification of arginine residues of apo B by
      cyclohexanedione treatment did not influence the ability of LDL to activate the
      phosphoinositide turnover in VSMC. It was found also that LDL are capable of
      activating cell-signalling systems in platelets of homozygous
      hypercholesterolemic patients and in VSMC from Watanabe rabbits lacking
      functional apo B,E-receptors. These data indicate that the "classical" high
      affinity LDL receptor does not mediate the activating effects of LDL on platelets
      and VSMC.

PMID- 7819412
TI  - [Atypical binding sites of low density lipoproteins in human vascular smooth
      muscle cells].
AB  - Lipoprotein-binding sites on cultured human omental vascular smooth muscle cells
      have been investigated. Two sites specifically binding low density lipoprotein
      (Kd1 = 1 microgram/ml and Kd2 = 50 micrograms/ml) were found. The properties of
      the high affinity site are similar to those of the previously described
      "classical" apo B,E-receptor. The nature of the second site is not clear. Binding
      to this low affinity site is saturable at physiological concentrations of LDL, is
      reversible and demonstrates a significant selectivity for LDL as compared to
      HDL3. In contrast with the apo B,E-receptor, the interaction of LDL with the low
      affinity site is not heparin-sensitive, does not require the presence of bivalent
      cations and is not abolished after modification of lysine residues of apo B. The
      kinetic characteristics of the LDL interaction with the low affinity site are in
      good correlation with the parameters of activation of second messenger systems.
      The Kd2 value of LDL binding is close to the LDL concentration inducing a half
      maximal elevation of inositol phosphates and cytoplasmic Ca2+ level. Acetylation
      or carbamylation of apo B does not influence the ability of LDL to activate cell
      signalling systems. Also, LDL-induced activation of the phosphoinositide turnover
      is not sensitive to heparin and EDTA. The data obtained support the hypothesis
      that the low affinity LDL-binding site mediates lipoprotein-induced activation of
      second messenger systems in human vascular smooth muscle cells.

PMID- 7819413
TI  - [Lipoxygenase oxidation of arachidonic acid in murine splenocytes and its
      modulation by the lactone ganglioside GM3].
AB  - The main arachidonic acid metabolites released into the medium by mouse
      splenocytes have been identified on the basis of chromatographic and spectral
      studies as well as by mass spectrometry of the derivatives. In the absence or
      presence of exogenous arachidonic acid mouse splenocytes produce mainly 12
      hydroxy-5,8,10,14-eicosatetraenoic and 12,20-dihydroxy-5,8,10,14-eicosatetraenoic
      acids. Both products are constantly released by intact cells into surrounding
      media without stimulation by exogenous substrate or other modulators. For the
      first time it is shown that exogenously added ganglioside GM3 lactone as well as
      ganglioside GM3 itself can influence the arachidonic acid metabolism in
      splenocytes.

PMID- 7819414
TI  - [Secreted serine proteinase from the spore-forming bacteria Bacillus intermedius
      3-19].
AB  - Extracellular serine proteinase has been isolated from the cultural medium of
      Bacillus intermedius 3-19 using CM-cellulose chromatography and affinity
      chromatography on bacitracin-Sepharose. The specificity of the proteinase with a
      wide range of natural and synthetic substrates has been investigated. The
      greatest activity was observed with tripeptides containing C-terminal Leu or Phe.
      The enzyme was completely inhibited by diisopropylfluorophosphate and partly
      inhibited by thiol-specific reagents. It is concluded that B. intermedius
      proteinase is a thiol-dependent serine proteinase pertaining to the subtilisin
      group. The amino acid composition of the enzyme has been determined. The enzyme
      contains one to three 1/2 cysteine residues, one of which is supposedly a Cys
      residue. The N-terminal amino acid sequences of the protein is AQTVPYGIPQIKAPA-.

PMID- 7819415
TI  - [Biochemical study of the A2F4 antigen associated with human pulmonary
      adenocarcinoma].
AB  - The tissue-specific antigen associated with human lung adenocarcinoma had been
      investigated using immunological and biochemical methods. The antigen, which
      represents a new tissue-specific marker, has a molecular weight of 400 kDa.
      Purification of the antigen was achieved by gel chromatography. Antibody binding
      to the antigen was studied using enzyme-linked immunoassay after preincubation
      with enzymes or treatment with periodate. The results obtained testify to the
      proteinaceous nature of the antigenic determinant and the glycoprotein nature of
      the antigen.

PMID- 7819416
TI  - [Kinetics of a single proteolysis stem. Proteolysis of ovalbumin].
AB  - The course of one-by-one proteolysis of ovalbumin was followed by determining the
      residual protein. The reactions were found to be of pseudo-first order. The
      parallel occurring zipper proteolysis had no effect on this result, since it
      brought about only the splitting of ovalbumin into large fragments without any
      split-off of TCA-soluble peptides. The one-by-one proteolysis was completed after
      the protein had been degraded into TCA-soluble peptides; further hydrolysis of
      the latter proceeded with deceleration. Obeying the pseudo-first order kinetics
      could not be due to reversible denaturation or local conformational changes
      preceding the proteolysis. The rate of the one-by-one proteolysis was limited by
      the rate of splitting of the first peptide bond in the protein molecule; its
      course could be described the integral form of the Michaelis-Menten equation. The
      conditions ([S0]/Km values), when the integral form of this equation was
      practically linear, were determined. It may be suggested that the true
      concentration of the protein conformers available to the proteolytic attack
      satisfies these conditions.

PMID- 7819417
TI  - [Participation of adenosine receptors in regulating the functional activity of
      neuronal chromatin by antifeines].
AB  - The regulatory pathways of chromatin transcription in neurons have been studied.
      The metabolic events (adenylate cyclase, Ca/phospholipid-dependent protein kinase
      C) involved in signal transduction via adenosine receptors were investigated with
      the application of pharmacological tools--the memory stimulant ethylnorantifeine
      and its structural analogs. It has been modelled the biochemical condition of A1
      and A2 adenosine receptors in the cortex and the striatum of rat brain. The
      antifeines did not influence AC of A1 or A2 receptors, unlike the non
      metabolizing adenosine derivatives -PIA, NECA and isobutylmethylcanthine. No
      direct effect of antifeines (10(-7)-10(-3) M) on membrane-bound protein kinase C
      was established. The data obtained failed to provide evidence for the antifeine
      effect on the functional activity of chromatin with regard to the triggering role
      of membrane acceptor systems. The possibility of direct control of the chromatin
      functional activity by neuroactive drugs is discussed.

PMID- 7819418
TI  - Quantitation of satellite cell proliferation in vivo using image analysis.
AB  - A nonisotopic, double fluorescence technique was developed to study myogenic
      satellite cell proliferation in posthatch turkey skeletal muscle. Labeled
      satellite cell nuclei were identified on enzymatically isolated myofiber segments
      using a mouse monoclonal antibody (anti-BrdU) followed by fluorescein-5
      isothiocyanate (FITC) conjugated goat anti-mouse IgG secondary antibody. Myofiber
      nuclei (myonuclei+satellite cell nuclei) were counterstained with propidium
      iodide (PI). The myofiber segment length, myofiber segment diameter, and the
      number of PI and FITC labeled nuclei contained in each segment was determined
      using a Nikon fluorescence microscope, a SIT video camera and Image-1 software.
      Data collected by three different operators of the image analysis system revealed
      5.0 +/- 1.4 satellite cell nuclei per 1000 myofiber nuclei and 5284 +/- 462
      microns3 of cytoplasm surrounding each myofiber nucleus in the pectoralis
      thoracicus of 9-week-old tom turkeys. BrdU immunohistochemistry coupled with the
      new approach of PI staining of whole myofiber mounts is an effective combination
      to allow the use of an efficient semi-automated image analysis protocol.

PMID- 7819419
TI  - A device for cutting brain slices.
AB  - A device for cutting brain slices is described as an alternative to cutting angle
      guides and the "brain macrotome." With this new device, slices of uniform
      thickness optimal for assessing morphological detail and photography can be
      produced. A similar but smaller device for cutting pieces of tissue for paraffin
      embedding is also presented. These devices should be useful in either the
      histopathology laboratory or mortuary.

PMID- 7819420
TI  - A technique for assessing the effects of pH and photodegradation on the stability
      of the iron chelate of ethyl N-methyl-4-hydroxy-5-oxo-3-pyrroline-3-carboxylate.
AB  - Ethyl N-methyl-4-hydroxy-5-oxo-3-pyrroline-3-carboxylate forms a deep red chelate
      with iron salts. The color intensity is directly related to the iron
      concentration. The photostability of the red color was determined at pH 1.2 and 5
      by spectrophotometric assay at 484 nm at intervals during irradiation by tungsten
      light at 1020 microW/cm2. After 528 hr of continuous irradiation in deionized
      water, 90.9% of the iron chelate had decomposed. The reaction followed zero order
      kinetics. Maximal stability was observed at pH 5 at both 10(-1) and 10(-2) molar
      concentrations of the iron chelate; no detectable decomposition occurred after
      192 hr of continuous irradiation. The iron chelate in biological tissues is
      stable for 18 months. The staining technique is superior to other histological
      methods for estimating low concentrations of iron in tissue.

PMID- 7819421
TI  - Fibrinogen: a diagnostic marker for early ischemia.
AB  - Although well established myocardial infarcts (MI) are not difficult to identify
      in routine hematoxylin and eosin stained sections, recent MI may present
      diagnostic problems. Fibrinogen is a useful marker for detecting early ischemic
      cell damage. Using immunofluorescence on frozen tissue, albumin, IgG and
      fibrinogen have been found throughout the sarcoplasm of ischemic fibers in human
      hearts. In this report, monoclonal antibodies to all three proteins were reacted
      using the avidin-biotin technique in formalin fixed, paraffin embedded sections
      from autopsy cases of sudden or intraoperative deaths with either subtle or no
      definite ischemic changes evident in routine sections. Strong staining of
      fibrinogen in the fibers associated with coagulative necrosis, contraction bands
      or wavy fibers, and in the fibers presumably associated with acute ischemia.
      Albumin and IgG staining was nonspecific. Fibrinogen is a reliable and
      reproducible marker for recognizing early ischemia. This method can be used to
      diagnose early sudden ischemic and intraoperative deaths due to coronary artery
      bypass graft and prosthesis-related complications and may be particularly useful
      for forensic autopsies.

PMID- 7819422
TI  - Microwaves applied to silver impregnations with ammoniacal silver carbonate.
AB  - Techniques for impregnation with ammoniacal silver carbonate provide valuable
      information on all types of tissue; however, the time investment required to
      impregnate a few sections has limited their application. We have shortened the
      impregnation times by using microwaves in techniques for reticular fibers,
      astrocytes, nerve fibers and chromaffin cells. The results were satisfactory with
      markedly reduced impregnation time and elimination of nonspecific silver
      deposits.

PMID- 7819423
TI  - Immunoenzymatic detection of collagen production by pulmonary fibroblasts in
      serum-free culture.
AB  - We have developed an improved assay for the production of collagen by
      fibroblasts. Early passage adult mouse lung fibroblasts, established and
      maintained in serum-free culture, were employed as the target cells. An enzyme
      immunoassay was used for detection of type I collagen deposited on the
      substratum, permitting adaptation of the technique to cultures in 96-well
      microplates. Approximately two-fold enhancement of collagen deposition was
      induced by exposure to a concentration of 3 ng/ml of transforming growth factor
      beta 1 or of 100 ng/ml of insulin-like growth factor-1 for 48 hr.

PMID- 7819424
TI  - Chemical dehydration for rapid paraffin embedding.
AB  - We describe chemical dehydration with 2,2-dimethoxypropane (DMP) for rapid
      paraffin embedding using a mixture of DMP and mineral oil followed by mineral oil
      as clearing intermediates. This method is useful for classical histological
      techniques as well as for histochemistry and immunocytochemistry.

PMID- 7819425
TI  - A method for isolating and preparing silica bodies in grasses for scanning
      electron microscopy.
AB  - Silica bodies are discrete deposits of dehydrated silica within epidermal cells.
      To describe these bodies completely, surrounding organic and unsilicified
      material must be removed. Methods generally used for isolating and preparing
      silica bodies were unsuitable for most grass species. An effective method for
      studying grasses is described here. After ashing the plant tissue, the ash was
      repeatedly rinsed with HCl in a specialized multiple funnel manifold and
      collected on Nuclepore filters. In addition, the silica bodies were sonicated for
      a few minutes to remove any remaining mineral impurities. Compared to
      conventional procedures, this method has a number of advantages: unsilicified
      material and mineral impurities were removed effectively, smaller quantities of
      plant tissue could be used, and the loss of silica bodies was minimized.

PMID- 7819426
TI  - Methenamine-silver staining: a simple and sensitive staining method for senile
      plaques and neurofibrillary tangles.
AB  - An improved methenamine-silver impregnation method is presented which exhibits
      sensitivity for amyloid substances comparable to that of anti-beta protein
      immunostaining. In optimally treated sections, this technique stained both beta
      amyloid deposits and neurofibrillary tangles, which are known to have a beta
      pleated structure. This simple procedure allows a large number of sections to be
      stained for routine examination.

PMID- 7819427
TI  - Reference materials and reference methods in laboratory medicine: a challenge to
      international cooperation.

PMID- 7819428
TI  - Clinical chemistry in Austria. Past--present--future. Reflections on the occasion
      of the 25th anniversary of the Austrian Society for Clinical Chemistry.

PMID- 7819429
TI  - Vitamin E compared with other potential risk factor concentrations in patients
      with and without coronary artery disease: a case-matched study.
AB  - Thirty six individuals with angiographic evidence of coronary atherosclerosis and
      thirty six individuals without coronary disease, matched for a variety of
      cardiovascular risk factors including age, sex, smoking, hypertension, diabetes
      and family history, were evaluated for their serum concentrations of vitamin E,
      total cholesterol, triacylglycerols, high density lipoprotein-cholesterol, low
      density lipoprotein-cholesterol, apolipoprotein A-I, and apolipoprotein B.
      Apolipoprotein B, low density lipoprotein-cholesterol and total cholesterol
      concentrations were unequivocally higher in patients with coronary artery
      disease. Triacylglycerols were marginally higher in patients with disease. The
      antioxidant vitamin E (alpha-tocopherol) was significantly higher in patients
      with atherosclerosis when compared with controls (35.1 +/- 17.0 mumol/l vs. 29.0
      +/- 13.2 mumol/l, p = 0.017). However, alpha-tocopherol concentrations were
      strongly associated with lipid concentrations and normalization to the total
      cholesterol concentrations produced ratios which were not significantly different
      in the two groups. Logistic regression analysis revealed that the association of
      lipid risk factors with coronary stenosis was determined primarily by the
      difference in total cholesterol values. This study demonstrated that in this
      group of patients referred for angiography and matched for other risk factors,
      higher alpha-tocopherol concentrations were associated with patients with
      coronary disease and were not useful for assessing risk of coronary artery
      disease.

PMID- 7819430
TI  - Immunoreactive creatine kinase-MB and creatine kinase isozyme concentrations
      during treatment of hypothyroid patients.
AB  - Using a highly sensitive enzyme immunoassay (EIA) system, we determined creatine
      kinase isozymes, namely creatine kinase-MB and creatine kinase-MM, in sera of
      patients suffering from primary hypothyroidism with concomitant signs of
      myocardial affections before and during treatment. After oral administration of L
      thyroxine, the augmented mass concentrations of serum creatine kinase-MB and
      creatine kinase-MM, and the increased catalytic activity concentrations of serum
      total creatine kinase and creatine kinase-MB gradually decreased in inverse
      proportion to the increased concentrations of serum triiodothyronine (T3) and
      thyroxine (T4). By the 6th to 8th week after treatment, the elevated levels of
      serum total creatine kinase and creatine kinase-MB catalytic activity
      concentrations (assayed by a routine method) and serum creatine kinase-MM mass
      concentrations (assayed by EIA) declined to normal values, while serum T3, T4,
      and thyroid stimulating hormone attained normal values. Serum creatine kinase-MB
      mass concentrations (assayed by EIA), however, still remained at the higher
      level, without complete recovery from myocardial damage, as shown by
      electrocardiogram (ECG). These data indicate that metabolic distortion still
      exists in the myocardium, as revealed by the high creatine kinase-MB mass
      concentration, especially as assayed by EIA, even though the plasma levels of
      thyroid hormones had returned to normal.

PMID- 7819431
TI  - Affinity chromatographic method for the extraction of ocytocin from human and rat
      plasma.
AB  - A procedure based on affinity chromatography for the extraction of ocytocin is
      described. Ocytocin antibody, covalently attached to a magnetizable iron
      suspension, retains its ability to bind ocytocin from blood plasma. The conjugate
      can be reused several times. Recovery of ocytocin was 60-70%, and the detection
      limit for the extraction assay was about 1 pg per tube. The specificity of the
      extraction method was characterized by HPLC/RIA on specimens extracted from blood
      plasma. The extracted material was found to be chomatographically identical with
      the reference ocytocin preparation. Comparison of RIA data for the same samples
      extracted by immunoextraction (y) and adsorption (x) showed a linear regression
      of y = 0.83 x + 2.12, r = 0.81, n = 17.

PMID- 7819432
TI  - [Long-functioning beta-D-glucose and L-lactate biosensors for continuous flow
      through measurements for "fouling"-resistant and selectivity-optimized serum- and
      hemoanalysis].
AB  - Bioelectrochemical membrane-electrodes for O2-sensitive enzymatic flow-through
      analysis of beta-D-glucose and L-lactate are described. The enzyme-membranes of
      the biosensors consist of glucose-oxidase or lactate-oxidase molecules cross
      linked with glutardialdehyde between two dialysis membranes. The accuracy of the
      biosensors is demonstrated by electroanalysis of diluted control serum and
      compared with redox-mediator-free H2O2 detection and photometric methods.
      Continuous haemoanalysis of uncoagulated blood was carried out, using an
      intermediate carrier stream with additive systems. Tangential streaming to the
      miniaturized dialysis chamber with a circular channel minimizes blockage of the
      pores of the dialysis membrane by erythrocytes, leukocytes or protein. An
      oxygenator pump for the exchange of gases between the buffered solution of the
      intermediate carrier and the surrounding atmosphere guarantees a constant oxygen
      partial pressure within the carrier stream. The pulsations produced by the
      oxygenator pump are dampened by a miniature pressure balance chamber with an
      unsignificant dead space volume for protecting the enzyme membrane of the sensor.
      Glutardialdehyde inhibits growth of microorganisms and any resulting oxygen
      consumption, so that even in protein-containing measuring solutions enzyme
      electrodes can be used without interference from microbial contamination. The
      bioelectrochemical measuring system can therefore also be employed for the
      electroanalysis of fermentation solutions. For continuous flow-through
      measurements, it is necessary to change the glucose-oxidase membranes after 100
      150 days, and the lactate-oxidase membranes after 3-6 weeks.

PMID- 7819433
TI  - Inulin measurement in serum and urine with an autoanalyser, corrected for glucose
      interference.
AB  - A method is described for the semi-automated measurement of inulin concentrations
      in serum and urine in the presence of glucose. The concentration of glucose is
      measured simultaneously and is used to correct for almost all "inulin-like"
      interferences. The inulin standard curve is linear over a wide range (5-2500
      mg/l). Between-run precision is < 6% and recovery from spiked sera is 98%. This
      method offers the possibility of measuring glomerular filtration rate in patients
      with varying glucose concentrations (e.g. diabetics).

PMID- 7819434
TI  - Use of plasma in serum tumour marker assays: cancer-associated serum antigen and
      mammary serum antigen.

PMID- 7819435
TI  - Multi-centre comparison of ABBOTT MATRIX Aero to Pharmacia Standard RAST,
      Modified RAST and skin puncture tests.
AB  - ABBOTT MATRIX Aero is an enzyme immunoassay which measures specific IgE
      antibodies to 14 individually calibrated airborne allergens using a single serum
      specimen. In this study, ABBOTT MATRIX performance was evaluated in comparison to
      the results of skin puncture test and the Standard and Modified RAST procedures.
      The ABBOTT MATRIX demonstrated overall sensitivity of 89% vs. Standard RAST and
      Modified RAST, with specificity greater than 92% vs. both methods. ABBOTT MATRIX
      sensitivity vs. skin test (71%) exceeded that of the Standard and Modified RAST
      procedures (62% and 67% respectively). Positive results reported by ABBOTT MATRIX
      but not RAST were corroborated by skin test results for 3 of 5 allergens
      evaluated. All in vitro systems demonstrated specificity of approximately 90% vs.
      skin test. The ABBOTT MATRIX system provided results which compared favorably
      with the results of skin test and RAST, but required less hands-on time to obtain
      quantitative specific IgE measurements to multiple allergens.

PMID- 7819436
TI  - Approved recommendation on IFCC methods for the measurement of catalytic
      concentration of enzymes. Part 8. IFCC Method for Lactate Dehydrogenase (l
      Lactate: NAD+Oxidoreductase, EC 1.1.1.27). International Federation of Clinical
      Chemistry (IFCC).

PMID- 7819437
TI  - Human sperm-zona pellucida interaction is inhibited by an antiserum against a
      hamster sperm protein.
AB  - During epididymal transit, mammalian spermatozoa acquire new surface antigens
      that may participate in gamete interaction. We have previously described a 26-kDa
      (P26h) epididymal hamster sperm protein that we propose to be involved in
      fertilization. In this study, we have searched for an antigenically related
      protein in the human, and have found that an anti-P26h antiserum recognizes a 34
      kDa (P34H) protein on Western blot of human sperm proteins. Immunostaining showed
      that this protein is localized on the acrosomal cap of human epididymal
      spermatozoa but not on testicular gametes. The effect of the anti-P26h antiserum
      on the fertilizing ability of human spermatozoa was evaluated by use of a human
      zona pellucida binding assay. Compared to the preimmune serum, the antiserum
      caused a highly significant decrease in the number of sperm bound per zona
      pellucida. This inhibition was not due to the induction of a premature acrosomal
      reaction nor to an effect on the motility of the spermatozoa. The antiserum
      recognizing the P34H human sperm protein had no effect on gamete fusion as
      determined by the zona-free hamster test. Our results suggest that the human
      spermatozoon acquires an epididymal protein that shares a common epitope(s) with
      the P26h hamster sperm protein. The possible involvement of this human sperm
      antigen in the binding to the zona pellucida is discussed.

PMID- 7819438
TI  - Localization and quantification of insulin-like growth factor-I (IGF-I) and IGF
      II/mannose-6-phosphate (IGF-II/M6P) receptors in pig embryos during early
      pregnancy.
AB  - To assess a potential role of insulin-like growth factor-I (IGF-I) and -II (IGF
      II) in early embryonic development, the presence of their receptors was
      investigated by both immunohistochemistry and autoradiography experiments on
      whole embryos at Days 4 and 6 of pregnancy, on embryo sections at Days 8 and 10,
      and on placenta at Day 20 of pregnancy. Immunohistochemistry experiments were
      performed by using specific polyclonal antibodies raised against human IGF-I and
      IGF-II/mannose-6-phosphate (IGF-II/M6P) receptors. By autoradiography,
      specificity of [125I]-IGF-I and [125I]-IGF-II binding on embryonic cells was
      assessed by competition with unlabeled IGF-I and IGF-II, and quantification of
      the autoradiographic signal was performed by image analysis. The presence of IGF
      I receptors on porcine trophectoderm cells was detected neither by
      immunohistochemistry nor by autoradioradiography on whole embryos or embryo
      sections. IGF-I receptors were present in the placenta at Day 20 of pregnancy,
      but only on endometrial cells. In contrast, IGF-II/M6P receptors were detected on
      porcine trophectoderm cells by both immunohistochemistry and autoradiography on
      whole embryos, on embryo sections at Day 8 and Day 10 of pregnancy, and on fetal
      and maternal compartments of the placenta at Day 20. The number of IGF-II/M6P
      receptors on trophectoderm cells was greatly heterogeneous between embryos within
      the same litters. There was no relationship between the number of IGF-II/M6P
      receptors on trophectoderm cells and the age or size of embryos between Day 8 and
      Day 10 of pregnancy. The involvement of the IGF-II/M6P receptor in early
      embryonic development in the pig remains to be determined.

PMID- 7819439
TI  - Analysis of the expression of growth factor, interleukin-1, and lactoferrin genes
      and the distribution of inflammatory leukocytes in the preimplantation mouse
      oviduct.
AB  - The oviduct provides the environment in which fertilization of the egg and
      subsequent development of the preimplantation mouse embryo occurs, but little is
      known about the oviduct's capacity to produce growth factors or cytokines that
      may influence these preimplantation events. Northern blot analysis and/or
      immunohistochemistry were employed to examine the expression or cellular
      distribution, respectively, of the growth factors heparin-binding epidermal-like
      growth factor (HB-EGF), transforming growth factor (TGF) alpha, epidermal growth
      factor (EGF), insulin-like growth factor-I (IGF-I), TGF beta 1, TGF beta 2, and
      TGF beta 3; of estrogen-regulated lactoferrin (LF); and of the cytokines
      interleukin (IL)-1 alpha and IL-1 beta in the mouse oviduct during the
      preimplantation period (Days 1-4 [Day 1 = vaginal plug]) and 7 days after
      ovariectomy. The results demonstrated that, except for EGF, each of the growth
      factors and the LF genes are expressed in the ampulla and isthmus regions of the
      oviduct throughout the preimplantation period. Prominent immunostaining in
      secretory epithelial cells was noted for HB-EGF, TGF alpha, IGF-I, TGF beta 1,
      and TGF beta 2, and LF. Less intense immunostaining in the serosa and/or smooth
      muscle was also noted for TGF alpha, IGF-I, and TGF beta 1. In contrast, intense
      immunostaining in smooth muscle was noted for TGF beta 2, and TGF beta 3 was
      detected exclusively in smooth muscle cells. The abundance of these mRNAs was
      relatively constant during the preimplantation period, and ovariectomy did not
      reduce the levels of these mRNAs. In contrast to these growth factors, the
      cytokine mRNAs examined (IL-1 alpha and IL-1 beta) were at or below the limits of
      detection under these experimental conditions, and inflammatory leukocytes (LF
      immunopositive neutrophils, IL-1 beta-immunopositive monocytes/macrophages, or
      peroxidase-positive eosinophils) were not detected in the oviduct, but were
      abundant in the adjacent uterine stroma on Day 1. These studies show that several
      growth factors are synthesized by the mouse oviduct and suggest that ovarian
      steroids do not play a major role in modulating expression of these genes in the
      oviduct during the preimplantation period. Furthermore, unlike the uterus on Day
      1, the oviduct does not exhibit an inflammatory response to mating.

PMID- 7819441
TI  - Removal of cytoplasmic lipid enhances the tolerance of porcine embryos to
      chilling.
AB  - The lipid content of porcine 1-cell stage embryos was reduced (delipated) through
      the use of micromanipulation to remove the lipid layer formed after
      centrifugation. Of 94 delipated embryos chilled to 4 degrees C for 1 h at the 1
      cell or 2- to 4-cell stage, 60 (64%) cleaved in culture with development to the
      morula-blastocyst stage, whereas all of the control embryos lysed within 24 h.
      Significantly more embryos developed beyond the 8-cell stage when they were
      chilled at the 2- to 4-cell stage compared with chilling at the 1-cell stage
      (44%, 20 of 45 vs. 18%, 9 of 49). Fewer embryos developed after chilling if they
      were only partially rather than fully delipated. Developmental rates of partially
      delipated embryos to the 8-cell and blastocyst stages were 33% (13 of 40) and 8%
      (3 of 40), rates significantly (p < 0.001 and 0.05) lower than the rate for fully
      delipated embryos (73%, 38 of 52 and 27%, 14 of 52, respectively). The in vitro
      developmental competence of the unchilled fully delipated embryos was comparable
      to that of intact zygotes (cleavage: 94%, 45 of 48 vs. 87%, 26 of 30; > or =
      blastocyst: 40%, 19 of 48 vs. 57%, 17 of 30). These data demonstrate that the
      sensitivity of porcine embryos to chilling is related to their high lipid content
      and that they can become tolerant to chilling if their lipid content is reduced.

PMID- 7819440
TI  - Recombinant human zona pellucida protein ZP3 produced by chinese hamster ovary
      cells induces the human sperm acrosome reaction and promotes sperm-egg fusion.
AB  - Studies on the role of specific molecules in the human fertilization process and
      additional assessments of potential applications for these proteins are hampered
      by the limited amount of available biological material. However, this drawback
      might be circumvented by the recent cloning of several gamete-specific genes,
      which opens possibilities for the production of recombinant proteins. By use of
      cDNA and genomic DNA fragments of the human ZP3 gene, which encodes a major
      constituent of the zona pellucida surrounding the oocyte, a 2.7-kb minigene was
      constructed containing the natural third and fourth introns of the gene and a
      truncated intron between exons 2 and 3. This ZP3 DNA was transfected to Chinese
      hamster ovary cells, and a single-cell clone producing the recombinant ZP3
      protein (recZP3) was generated. Western blot analysis of culture medium from
      these cells showed that recZP3 has a molecular mass +/- 5 kDa smaller than that
      of natural ZP3. Under reducing conditions, it migrates at an apparent molecular
      mass of 55-60 kDa. RecZP3 induced the sperm acrosome reaction and promoted fusion
      of human spermatozoa with zona-free hamster oocytes, indicating that the
      recombinant protein is biologically active. RecZP3 provides an attractive tool
      for studying the initial stage of the human fertilization process. Furthermore,
      it might have clinical applications in the development of diagnostic tests for
      male infertility and serve as target antigen in the design of contraceptive
      vaccines.

PMID- 7819442
TI  - Evaluation of growth, cell proliferation, and cell death in bovine corpora lutea
      throughout the estrous cycle.
AB  - To evaluate the kinetics of luteal growth, bovine CL were obtained from four
      stages (stage I, Days 1-4; stage II, Days 5-10; stage III, Days 11-17; stage IV,
      Days 18-21) of the estrous cycle, and luteal fresh weight as well as DNA,
      protein, and progesterone contents was determined. To evaluate the relative rate
      of cell proliferation, proliferating cell nuclear antigen (PCNA; a specific
      marker for cell proliferation) was immunolocalized in paraffin-embedded luteal
      tissue sections. To evaluate the relative rate of cell death, nucleosomal
      fragmentation of DNA (a specific marker for apoptosis) was detected by agarose
      gel electrophoresis and also by histochemical localization in paraffin-embedded
      luteal tissue sections. Luteal fresh weight and DNA, protein, and progesterone
      contents increased (p < 0.01) from stage I to stage II, were similar between
      stages II and III, and then decreased (p < 0.01) from stage III to stage IV. The
      ratio of protein to DNA (an index of average cell size) was similar for stages I,
      II, and III and then decreased (p < 0.01) at stage IV. For stage I (corpora
      hemorrhagica), most proliferating (PCNA-positive) cells were located in or around
      the core of the tissue infoldings (presumably thecal-derived areas), whereas
      relatively few proliferating cells were located at the periphery of the tissue
      infoldings (presumably granulosa-derived areas). For stages II, III, and IV, the
      majority of proliferating cells appeared to be small cells (i.e., small
      parenchymal cells, fibroblasts, and endothelial cells). The labeling index (LI;
      percentage of cells that were PCNA-positive) was greatest at stage I (20.3 +/-
      1.1%); it then decreased (p < 0.01) by stage II and was similar at stages II,
      III, and IV (3.4 +/- 1.1%). Apoptosis, as determined by evaluation of nucleosomal
      DNA fragmentation by agarose gel electrophoresis and in situ localization, was
      detectable only at stage IV. These data demonstrate that luteal growth from stage
      I to stage II resulted from cell proliferation as shown by a high LI at stage I,
      accompanied by increased luteal DNA content but no change in average cell size,
      and by similar protein: DNA ratios. Luteal regression from stage III to stage IV
      was primarily associated with cell deletion and decreased cell size as shown by a
      decrease in luteal DNA content and the appearance of apoptosis along with a
      decrease in the luteal protein: DNA ratio.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7819443
TI  - Use of low-salt culture medium for in vitro maturation of porcine oocytes is
      associated with elevated oocyte glutathione levels and enhanced male pronuclear
      formation after in vitro fertilization.
AB  - The effects of sodium chloride (NaCl) in Whitten's medium on intracellular
      glutathione concentration and on cytoplasmic maturation, as determined by
      monospermic penetration and male pronuclear formation of porcine oocytes, were
      examined. Porcine cumulus-oocyte complexes were cultured for 20 h in BSA-free
      Whitten's medium containing different NaCl concentrations (44.50, 68.49, 92.40,
      116.40, or 140.35 mM) and supplemented with 10% porcine follicular fluid and
      hormonal supplements; the complexes were then cultured without hormonal
      supplements for an additional 20-h period. The mean width of the perivitelline
      space of oocytes was increased with decreased concentration of NaCl in the
      culture medium. Intracellular glutathione concentration was elevated in oocytes
      cultured in medium with lower NaCl concentrations. After co-culture with
      spermatozoa for 6 h and culture in modified Whitten's medium for an additional 6
      h, there were no differences in maturation and penetration rates among
      experimental groups. However, the rate of male pronuclear formation was higher in
      oocytes matured in media with the lower NaCl concentrations. In addition, the
      rates of monospermic penetration and male pronuclear formation were higher in
      oocytes matured in medium containing 44.50 mM NaCl (59.3 +/- 8.1 and 70.9 +/-
      2.0%, respectively) than in medium containing 68.49 mM NaCl (39.4 +/- 5.5 and
      57.1 +/- 4.5%, respectively). These data indicated that decreasing NaCl
      concentration in maturation medium for porcine oocytes below the customary level
      improved the quality of the matured oocytes as reflected in higher intracellular
      glutathione content, wider perivitelline space, higher monospermic penetration
      rate, and increased frequency of male pronuclear formation.

PMID- 7819444
TI  - Uterine contractile responses to endothelin-1 and endothelin receptors are
      elevated during labor.
AB  - The purpose of this study was to determine whether the contractile responsiveness
      of the rat uterus to endothelin (ET)-1 and myometrial ET-1 receptors is elevated
      during labor. Uterine contractile responses to ET-1 were measured in isolated
      uterine strips obtained from rats on Day 18 of gestation, during spontaneous
      labor at term, and on Days 1 and 2 postpartum. The mean force (millinewtons)
      generated by cumulative addition of ET-1 (10(-10)-10(-6) M) was measured in
      vitro. Cumulative dose-response curves were created based upon the contractile
      activity vs. log doses of ET-1. The values of the estimated pD2, Emax, and slope
      of the dose-response curves were significantly (p < 0.05) higher in tissues taken
      during delivery than in tissues from animals on Day 18 of gestation or Days 1 and
      2 postpartum. Myometrial ET-1 receptors were also measured during pregnancy and
      labor. Scatchard analysis of the ET-1 binding to myometrial membranes revealed
      that receptor levels were significantly (p < 0.05) elevated in delivering
      animals, without changes in their affinity. Our study shows that the uterus is
      more sensitive and responsive to the contractile effects of ET-1 during labor, at
      term, when the receptor density is increased. The change in ET-1 responsiveness
      at term may play a role in the initiation and/or progression of labor.

PMID- 7819445
TI  - Epidermal growth factor inhibits large granulosa cell apoptosis by stimulating
      progesterone synthesis and regulating the distribution of intracellular free
      calcium.
AB  - The initial study was designed to determine whether all granulosa cells (GCs)
      undergo apoptosis in vitro. GCs were isolated from immature rat ovaries and
      separated on a 15-45% Percoll gradient. Twelve fractions were collected, and GCs
      were pooled according to size: small GCs (approximately 50 mu 2; fractions 2-5)
      and large GCs (> or = 75 mu 2; fractions 6-8). GCs were cultured in serum-free
      medium for 24 h. After 24 h of culture, fragmented DNA, detected by in situ end
      labeling of the 3'OH ends of DNA fragments, was observed within 70-80% of large
      GCs. Similarly, in situ DNA staining demonstrated that at least 50% of large GCs
      possessed apoptotic nuclei. These degenerative changes in DNA were observed
      within < or = 5% of small GCs. These studies demonstrate that in serum-free
      medium, most large GCs die via an apoptotic mechanism within 24 h. Subsequent
      studies focused on the mechanism by which epidermal growth factor (EGF) inhibits
      large GC apoptosis. EGF reduced the percentage of large GCs with apoptotic nuclei
      from 47 +/- 1% for controls to 18 +/- 2% (p < 0.05). EGF also increased
      progesterone (P4) secretion from large GCs (6.3 +/- 0.7 for controls vs. 18.7 +/-
      1.0 ng/ml for EGF treatment; p < 0.05). The effect of EGF on apoptosis was
      mimicked by P4 and attenuated by the P4 antagonist, RU 486, and aminoglutethimide
      (AG), an inhibitor of P4 synthesis. The effect of AG was overridden by P4.
      Therefore, EGF reduces large GC apoptosis by stimulating P4 synthesis, with P4
      mediating its action through its receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7819446
TI  - Steroidogenesis in the preovulatory porcine follicle.
AB  - The expression of four major steroidogenic enzymes in porcine theca and granulosa
      cell layers of preovulatory follicles was related to the levels of steroids in
      follicular fluid and gonadotropin concentrations in peripheral serum at
      slaughter. Ovaries were collected during proestrus, early estrus, and late estrus
      as evidenced by behavioral signs. Follicles were dissected from the ovaries, and
      theca, granulosa, and follicular fluids were pooled for each of 24 sows.
      Cytochromes P450 17 alpha-hydroxylase/17-20 lyase (P450c17), aromatase (P450arom)
      and side-chain cleavage (P450scc), as well as 3 beta-hydroxysteroid dehydrogenase
      (3 beta HSD), were subjected to Northern and Western immunoblot analyses. The
      concentrations of estradiol-17 beta, testosterone, androstenedione, and
      progesterone were determined in follicular fluid, and peripheral serum was
      assayed for estradiol-17 beta, LH, and FSH. Stages of preovulatory development
      were verified by plasma levels of LH, FSH, and estradiol-17 beta. Thecca
      expressed P450c17, P450arom, P450scc, and 3 beta HSD whereas granulosa expressed
      only P450arom and low levels of P450scc. Thecal P450c17, thecal P450arom, and
      granulosa P450arom expression decreased coincidentally as serum estradiol-17 beta
      and follicular fluid estradiol-17 beta, testosterone, and androstenedione levels
      declined after the presumed gonadotropin surge. Unlike P450c17 and P450arom
      P450scc and 3 beta HSD remained relatively constant in theca and granulosa. From
      these data, we suggest that the theca interna may be the primary steroidogenic
      compartment of the porcine follicle during its final stages of preovulatory
      development. Moreover, preovulatory estrogen secretion appears to be controlled
      by the coordinated expression of a triad of enzymes in the porcine follicle that
      includes theca P450c17, theca P450arom and granulosa P450arom.

PMID- 7819447
TI  - Interleukin-1 receptor antagonist suppresses human chorionic gonadotropin-induced
      ovulation in the rat.
AB  - Indirect evidence has implicated the interleukin-1 (IL-1) system in ovulation.
      Thus, the ability of IL-1 beta to induce ovulation in rat and rabbit perfused
      ovaries has been demonstrated. In the present study, the involvement of the IL-1
      system in ovulation was directly tested in vivo, in the rat model. For this
      purpose, the natural inhibitor of the IL-1 system, interleukin-1 receptor
      antagonist (IL-1ra), was administered locally by use of an intrabursal injection
      route. Twenty-six-day-old Sprague-Dawley rats received injections of eCG (10 IU),
      followed 56 h later by hCG (15 IU). IL-1ra (75 micrograms/bursa) was administered
      locally into the periovarian sac, 6 h (n = 5), 2 h (n = 11), and 0 h (n = 5)
      before hCG administration. Control animals (n = 10) received injections of the
      same volume (50 microliters) of vehicle (PBS). IL-1ra administered locally into
      the periovarian sac inhibited ovulation from the treated ovary, reaching 40%
      inhibition (p < 0.05) when injected 2 h prior to hCG, as compared to the
      untreated contralateral ovary (6 +/- 1.4 ova vs. 10 +/- 1.8 ova) and PBS-injected
      control ovaries (6 +/- 1.4 ova vs. 8.2 +/- 0.7). Injection of IL-1ra 6 h before
      or concomitantly with hCG did not affect the ovulation rate. Internucleosomal DNA
      fragmentation was evaluated by 3' end-labeling and autoradiography for detecting
      apoptotic changes. No difference in DNA fragmentation was found between treated
      and untreated ovaries.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7819448
TI  - Effect of diet on the clearance of estradiol-17 beta in the ewe.
AB  - The twinning rate of ewes is poorly related to plasma concentrations of
      gonadotropins. In this study, we tested an alternative hypothesis for the control
      of twinning rate, by testing whether nutritional treatment sufficient to affect
      twinning could alter estrogen metabolism, with a particular focus on the
      enterohepatic recirculation. Groups of 5 ovariectomized ewes were fed either
      above maintenance (supplemented) or below maintenance (restricted). The
      metabolism of estradiol-17 beta was examined by following the fate of a single
      i.v. injection of 1.45 micrograms [3H]estradiol-17 beta. In both groups, 74% of
      the radioactivity was recovered from the feces within 10 days, predominantly as
      free estradiol-17 alpha, but excretion was slower in the nutritionally restricted
      ewes. A further 6% of injected radioactivity was excreted in the urine, mostly
      within 24 h, with no effect of dietary group. Radioactivity in plasma was
      characterized by ion-exchange chromatography and HPLC. Within 30 min of
      injection, the main circulating radioactive compound was estradiol-17 alpha
      sulfate. This remained at a greater concentration than free steroid for the next
      48 h, and was greater after 16 h (p < 0.05) in plasma of nutritionally restricted
      ewes than in the supplemented group. At 0.5 and 2 h, the free steroid was almost
      entirely estradiol-17 beta, but a polar compound, which appeared by 4 h and
      probably arose by recirculation from the intestine, remained the major
      unconjugated metabolite in plasma for the next 24 h. Plasma concentrations of
      this compound were higher (p < 0.05) in the restricted ewes than in the
      supplemented ewes during this period.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7819449
TI  - Age- and lobe-specific responses of the brown Norway rat prostate to androgen.
AB  - We examined the effects of age and of increasing concentrations of testosterone
      on the wet weight, protein content, cell number, and cell size of the ventral,
      dorsal, and lateral lobes of the Brown Norway rat prostate. Young (3 mo of age)
      and aged (15, 17, and 21 mo of age) rats received implants of increasing sizes of
      testosterone-filled Silastic capsules for 3 mo. Wet weights of the prostate were
      the same in untreated young (6-mo-old) and aged (18-24-mo-old) rats. Testosterone
      administration resulted in serum testosterone concentrations ranging from
      physiologic to superphysiologic. Dose-dependent increases in wet weights and
      protein contents were seen in the ventral, dorsal, and lateral prostatic lobes of
      both young and aged rats. For each given dose of testosterone, including doses
      that resulted in serum testosterone concentrations within the physiologic range,
      the weights and protein contents of the dorsal and lateral lobes were greater in
      old (24-mo-old) than in young (6-mo-old) rats, indicating an effect of age in
      these lobes. In contrast, ventral prostate weights and protein contents increased
      equivalently in young and aged rats with increasing testosterone concentration.
      DNA content, a measure of cell number, increased significantly in the dorsal and
      lateral lobes as a function of testosterone dose and age, but in the ventral lobe
      did not differ with testosterone dose or age. Quantitative morphologic analyses
      showed significant hypertrophy of epithelial cells throughout each of the three
      lobes in both young and aged rats treated with testosterone. Taken together,
      these results indicate that the prostate of Brown Norway rats shows age and lobe
      specific responses to androgen with respect to wet weight, protein content, cell
      number, and cell morphology.

PMID- 7819450
TI  - Complementary deoxyribonucleic acid cloning and molecular characterization of an
      estrogen-dependent human oviductal glycoprotein.
AB  - A 120-kDa oviduct-specific glycoprotein is synthesized and secreted into the
      oviductal lumen during estrogen dominance in the human. The objective of this
      investigation was to clone, sequence, and characterize the cDNA to this core
      protein. Rapid amplification of cDNA ends was used to clone a contiguous 3' CDNA
      end and 5' cDNA end. The total length of the cDNA was determined to be 2.2 kb by
      sequence analysis and exhibited a 92% sequence identity with the comparable
      overlapping baboon cDNA (1.2 kb). A high degree of homology was found to the N
      terminal sequence of hamster oviductin and the partial sequence of a homologous
      baboon and bovine oviduct glycoprotein. Northern blots revealed a single mRNA
      species of 2.4 kb. Using RNA from various tissues of an estrogen-treated baboon,
      we found that the mRNA for the oviductal glycoprotein was present only in the
      oviduct. Hybridization was detected to an mRNA of similar size from oviductal
      tissue of the baboon, hamster, and mouse and to an mRNA of slightly smaller size
      in the rabbit, cow, and cat but not to any mRNA species from rat oviductal RNA.
      Slot-blot analysis showed that the message was present in significantly greater
      (p < 0.05) concentrations in RNA from oviductal tissue from the late follicular
      stage than from the early follicular, early or late luteal, or postpartum stages.
      In conclusion, we have isolated the complete cDNA for a human oviductal
      glycoprotein. The presence of significantly greater amounts of the mRNA during
      the late follicular phase of the menstrual cycle is consistent with the proposed
      estrogen control. The mRNA for the oviductal glycoprotein is present only in the
      oviduct of an estrogen-treated baboon, and a cross-hybridizing RNA is found in
      oviductal RNA from various mammals.

PMID- 7819451
TI  - Identification of the Ped gene at the molecular level: the Q9 MHC class I
      transgene converts the Ped slow to the Ped fast phenotype.
AB  - The Ped (preimplantation embryo development) gene, which maps to the Q region of
      the mouse major histocompatibility complex (MHC), controls the rate of cleavage
      division of preimplantation mouse embryos and subsequent embryonic survival. Of
      the ten known MHC class I genes in the Q region of the mouse MHC, four--Q6, Q7,
      Q8, and Q9--are almost identical and encode similar proteins, all called the Qa-2
      antigen. Previous studies have suggested that the Q9 gene encodes the Ped gene.
      To test this directly, one-cell embryos from the CBA/Ca strain (Ped slow) that is
      missing the Q9 gene and the Qa-2 antigen were injected with the Q9 gene from the
      C57BL/10 strain (Ped fast) that possesses the Q9 gene and expresses the Qa-2
      antigen. The resulting Q9 transgenic mice were found to express the Qa-2 antigen.
      In addition, it was found that introduction of the Q9 gene converted the Ped gene
      phenotype of the recipient strain from slow to fast. Therefore, the Ped gene
      product is the Qa-2 antigen encoded by the Q9 gene.

PMID- 7819452
TI  - Effects of interferon-tau and interferon-alpha on proliferation of bovine
      endometrial cells.
AB  - The ruminant conceptus secretes a unique interferon, interferon-tau, that
      regulates endometrial prostaglandin secretion during early pregnancy. Because one
      of the pleiotropic effects of interferons is to inhibit cellular proliferation, a
      series of experiments was conducted to determine whether or not the bovine
      endometrium is sensitive to the antiproliferative effect of interferon-tau and
      the related interferon, interferon-alpha. Endometrial epithelial and stromal
      cells were prepared from the endometrium of cows from Days 11-17 after estrus and
      incubated with recombinant bovine interferon-tau (rbIFN tau; 1-1000 ng/ml),
      recombinant bovine interferon-alpha 1 (rbIFN alpha; 1-1000 ng/ml), recombinant
      human interferon-alpha 2b (rhIFN alpha; 100 ng/ml), or ovine interferon-tau (oIFN
      tau; 100 ng/ml). Proliferation was determined by monitoring uptake of
      [3H]thymidine into DNA. Generally, interferons did not inhibit proliferation of
      endometrial epithelial cells. Exceptions were for 1000 ng/ml rbIFN tau, which
      inhibited proliferation by 23%; 100 ng/ml rbIFN alpha, which inhibited
      proliferation by 28% in one of two experiments only; and 100 ng/ml oIFN tau,
      which inhibited proliferation by 17%. Proliferation of endometrial stromal cells
      was not inhibited by any concentration of any interferon in two separate
      experiments. Therefore, unlike other bovine cells tested previously (lymphocytes
      and oviductal cells), bovine endometrial cells were not consistently inhibited by
      IFN tau or IFN alpha. Such reduced responsiveness of endometrial cells to the
      antiproliferative effects of type I interferons could allow for growth of the
      endometrium during the period of pregnancy when the conceptus produces IFN tau.

PMID- 7819453
TI  - Developmental expression of testis messenger ribonucleic acids in the rat
      following propylthiouracil-induced neonatal hypothyroidism.
AB  - Propylthiouracil- (PTU) induced transient neonatal hypothyroidism increases adult
      rat testis weight 80-100%; this effect involves prolongation of Sertoli cell
      proliferation. To gain insight into developmental effects of PTU on the testis,
      we used Northern analysis to examine chronological expression of Sertoli cell
      mRNA in postnatal rat testes from rats that were untreated (controls) or were
      given PTU from birth to Day 25. Treated rats showed prolonged early expression of
      genes associated with dividing Sertoli cells such as MIS (Mullerian inhibiting
      substance) and c-erbA alpha (thyroid hormone receptor). Expression of several
      other Sertoli cell mRNAs (androgen-binding protein [ABP], clusterin, and inhibin
      beta B) was delayed, as was that of hemiferrin, a spermatid-specific mRNA.
      Temporal expression patterns for other mRNAs (sulfated glycoprotein [SGP]-1,
      transferrin, and inhibin-alpha) were similar in control and treated animals.
      Additionally, thyroid hormone replacement in PTU-treated animals decreased MIS
      and c-erbA alpha mRNA expression to control levels. The altered developmental
      pattern of expression of a number of major Sertoli cell genes reflects a
      prolonged mitogenesis and delayed maturation of Sertoli cells in neonatally
      hypothyroid animals. Furthermore, our results suggest that thyroid hormone may
      directly potentiate molecular events associated with cessation of Sertoli cell
      proliferation and maturation during early testis development.

PMID- 7819454
TI  - Photoperiodic responses in Djungarian hamsters (Phodopus sungorus): importance of
      light history for pineal and serum melatonin profiles.
AB  - Male Djungarian hamsters with previous light experience of long photoperiods of
      16 h of light per day (16L:8D) or short photoperiods (8L:16D) were transferred
      either to the opposite photoperiods or to intermediate photoperiods (14L:10D). It
      was demonstrated that the same intermediate photoperiod could exert inhibitory or
      stimulatory effects on coat color, body weight, and the reproductive system,
      dependent on the previous light history. The response was graduated in accordance
      with the degree of change in day length. Despite opposite responses to the same
      photoperiod, diurnal patterns of melatonin in the pineal glands were identical.
      However, the circadian melatonin pattern in serum of photoinhibited hamsters had
      a more pronounced nighttime elevation than that found in the serum of
      photostimulated animals. In hamsters nonresponsive to short photoperiods, no
      proper short-day pattern was found. Melatonin production is a highly dynamic
      process, causing concentration shifts in the pineal gland and changes in the
      serum amplitude during prolonged exposure to short photoperiods. The different
      reactions to identical photoperiods are associated with different serum melatonin
      patterns, as shown here for the first time.

PMID- 7819455
TI  - Luteinizing hormone and prolactin in mated female meadow voles housed in long and
      short day lengths.
AB  - Fertility differs dramatically between female meadow voles (Microtus
      pennsylvanicus) housed in long (LD; 14 h light/day) and short (SD; 10 h
      light/day) day lengths. All mated LD females ovulate, and 75-100% produce
      litters. In contrast, 40% of SD females that mate only after long contact with a
      male do not ovulate, and fertility for SD females is much lower (30-40% produce
      litters overall). Because copulation causes the surge in LH required for
      ovulation and the increase in prolactin (PRL) needed to maintain corpora lutea,
      we hypothesized that SD females might have lower ovulation rates and litter
      production because of inadequate hormonal responses. Serum LH was measured 24 h
      before, and 30, 60, 90, 120, and 180 min after, mating. Prolactin was measured
      before, and 24 and 48 h after, copulation. LD and SD females that ovulated
      demonstrated a sharp increase in LH levels at 30 and 60 min post mating, but LH
      in non-ovulating females was approximately 50% lower than that of ovulating
      females at 30 and 60 min post mating. PRL in LD females was double baseline
      levels at 24 and 48 h after mating. PRL in SD females increased at 24 h, but
      declined to pre-mating levels by 48 h post mating. These data suggest that
      reduced fertility in short day lengths in female voles may be related to two
      separate problems: 1) The rise in LH following copulation is insufficient in some
      females to cause ovulation. 2) PRL may not remain elevated long enough to support
      functional corpora lutea in some females that ovulate.

PMID- 7819456
TI  - Theca cell cytochrome P450 17-hydroxylase and aromatase messenger ribonucleic
      acid abundance and serum steroid levels during follicular atresia associated with
      incubation behavior in the domestic turkey hen.
AB  - This study was designed to examine changes in cytochrome P450 17 alpha
      hydroxylase (C17) and aromatase (ARO) mRNA contents in the theca layer of
      preovulatory follicles (POF) as turkey hens transit from egg laying to
      incubation. Hens were grouped into the following categories: 1) laying hens--laid
      one egg per day and nested 1-2 times per day; 2) transitional hens--laid one egg
      per day and nested > 4 times per day; and 3) Day 1, Day 3, and Day 5 incubating
      hens--laid no eggs for 2, 4, or 6 days, respectively, and nested > 4 times per
      day. Small white follicles (SWF) and the theca layer from the largest (F1) and
      the third (F3), fifth (F5), and seventh (F7) largest POF were dispersed and
      challenged with testosterone (T) for 5 h. Relative levels of C17 and ARO mRNA
      were examined from the theca layers of F1, F3, F5, F7, and SWF. The number of
      atretic follicles increased from 0 (layers) to 8 (Day 5 incubating hens). Serum
      LH, progesterone (P), and estradiol (E), but not T, declined on Day 1 of
      incubation. Basal levels of P, T, and E from theca and SWF cells declined in
      incubating hens. Both basal and T-stimulated theca and SWF production of E
      decreased in incubating hens. C17 and ARO mRNA declined in SWF, F7, and F5 during
      follicular atresia. It is suggested that reduced gene expression of ovarian
      steroidogenic enzymes may be a partial determinant of reduced circulating sex
      steroid levels in incubating hens.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7819457
TI  - Effect of the conceptus and lack of effect of uterine space on endometrial
      protein secretion during mid-gestation in swine.
AB  - The effect of the conceptus and of reduced uterine space on endometrial protein
      secretion was examined on Days 40, 60, and 80 of gestation in white crossbred
      gilts. Twenty-nine gilts were checked daily for estrus, and 15 were given 5 mg
      estradiol valerate daily from Days 11 to 15 (Day 0 = day of estrus) of the
      estrous cycle to induce pseudopregnancy. The remaining 14 pigs were mated during
      estrus. All pigs were laparotomized on Day 4, and one uterine horn was ligated to
      produce one crowded and one roomy uterine environment. Pigs were killed on Days
      40, 60, and 80 of pregnancy or pseudopregnancy. The reproductive tracts were
      collected, and placental tissues from pregnant pigs and endometrial tissues from
      all pigs were cultured in the presence of 3H-leucine to evaluate protein
      secretion. Conditioned medium was dialyzed, measured for incorporation of
      radioactivity into nondialyzable macromolecules, and then subjected to two
      dimensional (2D)-PAGE to determine the effect of uterine space and day of
      pregnancy or pseudopregnancy on overall protein secretion rate and secretion of
      specific proteins. Fetal survival, fetal weight, and placental weight were
      decreased (p < 0.01) in the crowded uterine environment compared to the roomy
      uterine environment. Incorporation of 3H-leucine into nondialyzable
      macromolecules by endometrial tissue in culture was not affected by uterine
      space. Secretion of nondialyzable macromolecules by endometrium from pregnant
      pigs was not different from that by endometrium from pseudopregnant pigs on Day
      40 but was greater (p < 0.01) on Days 60 and 80.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7819458
TI  - Prostaglandin production during spontaneous labor and after treatment with RU486
      in pregnant rhesus macaques.
AB  - The production of prostaglandins from amnion, chorion, decidua, and myometrium
      was studied in a superfusion system to determine the level of prostaglandin
      production during late pregnancy, during spontaneous labor, and after in vivo
      treatment with RU486. Tissues were divided into three groups: those from pregnant
      control animals, those from animals receiving RU486 (20 mg/kg/day for 3 days) in
      vivo, and those from animals in spontaneous term labor. Tissues were collected at
      cesarean section and placed in the superfusion system. After a 30-min
      equilibration period, fractions of media were collected after passing through the
      tissue chambers and were assayed for prostaglandin F2 alpha (PGF2 alpha) and
      prostaglandin E2 (PGE2). The results showed a significant increase in PGF2 alpha
      from decidua of animals treated with RU486 compared to pregnant controls
      (pregnant: 3.01 +/- 0.45 ng/g/min; RU486: 4.45 +/- 0.28 ng/g/min; p < 0.05).
      There was a dramatic increase in PGE2 production by amnion from animals in
      spontaneous labor but not after RU486 treatment (pregnant: 0.21 +/- 0.06
      ng/g/min; RU486: 0.56 +/- 0.09 ng/g/min; spontaneous labor: 5.83 +/- 0.43
      ng/g/min; p < 0.01). We conclude that while progesterone is important for
      maintaining uterine quiescence during pregnancy, progesterone receptor blockade
      by RU486 does not lead to an increase in PGE2 production by amnion as is shown
      during normal spontaneous labor.

PMID- 7819459
TI  - Comparative aspects of steroid hormone metabolism and ovarian activity in felids,
      measured noninvasively in feces.
AB  - Noninvasive fecal assays were used to study steroid metabolism and ovarian
      activity in several felid species. Using the domestic cat (Felis catus) as model,
      the excretory products of injected [14C]estradiol (E2) and [14C]progesterone (P4)
      were determined. Within 2 days, 97.0 +/- 0.6% and 96.7 +/- 0.5% of recovered E2
      and P4 radioactivity, respectively, was found in feces. E2 was excreted as
      unconjugated estradiol and estrone (40%) and as a non-enzyme-hydrolyzable
      conjugate (60%). P4 was excreted primarily as non-enzyme-hydrolyzable, conjugated
      metabolites (78%) and as unconjugated pregnenolone epimers. A simple method for
      extracting fecal steroid metabolites optimized extraction efficiencies of the E2
      and P4 excretion products (90.1 +/- 0.8% and 87.2 +/- 1.4%, respectively).
      Analysis of HPLC fractions of extracted fecal samples from the radiolabel
      injected domestic cats revealed that E2 immunoreactivity coincided primarily with
      the unconjugated metabolized [14C]E2 peak, whereas progestogen immunoreactivity
      coincided with a single conjugated epimer and multiple unconjugated pregnenolone
      epimers. After HPLC separation, similar immunoreactive E2 and P4 metabolite
      profiles were observed in the leopard cat (F. bengalensis), cheetah (Acinonyx
      jubatus), clouded leopard (Neofelis nebulosa), and snow leopard (Panthera uncia).
      Longitudinal analyses demonstrated that changes in fecal E2 and P4 metabolite
      concentrations reflected natural or artificially induced ovarian activity. For
      example, severalfold increases in E2 excretion were associated with overt estrus
      or exogenous gonadotropin treatment, and elevated fecal P4 metabolite
      concentrations occurred during pregnant and nonpregnant (pseudopregnant) luteal
      phases. Although overall concentrations were similar, the duration of elevated
      fecal P4 metabolites during pseudopregnancy was approximately half that observed
      during pregnancy. In summary, steroid metabolism mechanisms appear to be
      conserved among these physically diverse, taxonomically related species. Results
      indicate that this hormone-monitoring approach will be extremely useful for
      elucidating the hormonal regulatory mechanism associated with the reproductive
      cycle, pregnancy, and parturition of intractable and endangered felid species.

PMID- 7819460
TI  - Avian granulosa cell prostaglandin secretion is regulated by transforming growth
      factor alpha and beta and does not control plasminogen activator activity during
      follicular development.
AB  - The aim of the present study was to determine the role of transforming factor
      alpha (TGF alpha) and beta (TGF beta) in the regulation of prostaglandin (PG)
      secretion, and the relationships between PG and plasminogen activator (PA)
      activity in hen granulosa cells during ovarian follicular development. Cells from
      the first (F1), third (F3), and fifth and sixth (F5-6) largest preovulatory
      follicles were cultured for up to 21 h in the presence of TGF alpha (0.1-10
      ng/ml) and/or TGF beta (4-20 ng/ml) or TGF alpha together with a cyclooxygenase
      inhibitor, indomethacin (0.05-0.5 microM). The release of PG into the incubation
      medium was determined by RIA. Cell-associated (PAc) and secreted (PAs) PA
      activities were measured by a fibrinolysis assay and characterized by zymography.
      Basal PGF secretion from F1, F3, and F5-6 cells was 2.2 +/- 0.3, 2.2 +/- 0.5, and
      1.1 +/- 0.3 ng/micrograms DNA, respectively, and was higher than that of PGE.
      Basal total PA (PAc+PAs) activity from F1, F3, and F5-6 cells was 41 +/- 13,261
      +/- 68, and 958 +/- 268 x 10(3) cpm/micrograms DNA, respectively. TGF alpha
      stimulated PG secretion and PA activity in a dose-dependent manner. The TGF alpha
      induced PA activity was predominantly associated with a molecular mass of 30-35
      kDa, corresponding to that of urokinase PA. The stimulation of PG secretion by
      TGF alpha was maximal in F3 and F1 granulosa cells whereas PA activity in the
      presence of TGF alpha was highest in cells from F5-6 follicles.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7819461
TI  - Effect of macromolecules from oviductal conditioned medium on bovine sperm motion
      and capacitation.
AB  - The effect of macromolecules from oviductal conditioned medium (CM) on sperm
      motility and capacitation was studied. Sperm pooled from three bulls was
      incubated in either luteal isthmic CM, luteal ampullary CM, estrual isthmic CM,
      estrual ampullary CM, or control medium (no CM) for 4 h. Sperm capacitation and
      motility were assessed at 10 min and 4 h. Estrual isthmic CM capacitated
      significantly more spermatozoa at 4 h than estrual ampullary CM or control
      medium. CM also affected lateral head movement (ALH) and beat cross-frequency
      (BCF) of sperm. In a second experiment, the glycosaminoglycan (GAG) content of
      the different types of oviductal CM was quantified. Estrual isthmic CM contained
      more GAG than estrual ampullary CM. Among luteal samples, no difference in GAG
      concentration between the isthmic and ampullary CM was found. Heat treatment (100
      degrees C) of oviductal CM before coincubation with sperm significantly reduced,
      but did not eliminate, the capacitating ability. Because heat treatment denatures
      proteins and decreases the capacitating ability of certain GAG, we concluded that
      the capacitating effect of estrual isthmic CM may be associated with proteins,
      GAG, and proteoglycans in the CM. Isthmic secretions may play a major role during
      in vivo sperm capacitation, given that bovine spermatozoa may reside in the
      oviduct isthmus for up to 18 h before fertilization.

PMID- 7819462
TI  - Protein kinase C second messenger system mediates the antisteroidogenic effects
      of prostaglandin F2 alpha in the ovine corpus luteum in vivo.
AB  - Experiment I was designed to determine the optimal dose of phorbol 12-myristate
      13-acetate (PMA) that inhibited progesterone production when infused into the
      ovarian artery. The most efficacious dose of PMA was 2 mumol. Experiment II was
      designed to determine whether activation of protein kinase C (PKC) inhibited
      progesterone production without initiating luteolysis. Ewes received ovarian
      arterial infusions of 4 alpha-phorbol (2 mumol, n = 4), PMA (2 mumol, n = 8), or
      prostaglandin F2 alpha (PGF2 alpha; 1 mumol, n = 5). Concentrations of
      progesterone in serum decreased by 3 h in PMA-treated ewes and by 5 h in PGF2
      alpha treated ewes (p < 0.05). By 48 h, serum levels of progesterone in PMA
      treated ewes had returned to control values; but in PGF2 alpha-treated ewes they
      remained low for the duration of the experiment. Luteal weights and progesterone
      contents at 48 h were similar in 4 alpha-phorbol- and PMA-treated ewes but were
      decreased in PGF2 alpha-treated ewes (p < 0.05). Experiment III was designed to
      determine whether PGF2 alpha or PKC activation induced oligonucleosome formation
      or influenced mRNA levels for cytochrome P450sec or 3 beta-hydroxysteroid
      dehydrogenase/delta 5-delta 4 isomerase (3 beta-HSD). Ewes received treatments as
      in experiment II, and CL were collected at 3, 12, or 24 h (n = 3-4 per group).
      Luteal weights were decreased (p < 0.05) and oligonucleosome formation was
      increased (p < 0.05) in PGF2 alpha-treated ewes compared to controls or to PMA
      treated ewes by 12 h.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7819463
TI  - [Timely anesthesiologic management of hip prosthesis patients].

PMID- 7819464
TI  - [Total hip endoprostheses--characteristic aspects from the anesthesiologic
      viewpoint].
AB  - Total hip replacement is a frequently practised operation. Depending on age,
      circumstances and individual assessment, cemented, non-cemented and hybrid forms
      are used. Apart from general risks, such as vascular and/or neural injuries,
      thrombosis and infections, there are specific risks, depending on the surgical
      technique. If cemented systems are used, the anesthesiologist must be on the
      alert in respect of a possible multi-causal cardiopulmonary depression during the
      implantation of the prosthesis. Incidents may be reduced or moderated by measures
      such as reduction of pressure from the femoral cavity or anesthetic measures such
      as avoidance of N2O during or after cementation, use of anti-histamines, etc.,
      but there is no absolute protection from severe reactions by the cardiopulmonary
      system. In these cases it is imperative to recognise and treat hypoxic conditions
      immediately, whatever the cause, such as cardiac or pulmonary depression. If a
      non-cemented hip replacement is used or a revision is necessary the main problem
      is usually a higher blood loss. Especially in such cases it is necessary to apply
      a well-organised sequence of blood-saving methods to protect patients from the
      general risks of homologous blood transfusion. Even though the main concern of
      the public is the possibility of contamination of donor blood with the AIDS
      virus, transmission of hepatitis C virus is a much more common problem. Depending
      on the diagnostic methods the occurrence of thrombosis after total hip
      replacement has been reported to be as much as 55%. To minimise this high
      incidence, sufficient prophylaxis, adequate fluid therapy, suitable anesthetic
      techniques and cutting down on the duration of the operation should be taken into
      account. The use of low molecular weight heparins has certain advantages. If deep
      vein thrombosis has occurred, therapy consists of anticoagulation with
      intravenous heparin and immobilisation. A rare but severe complication is a deep
      hip prosthetic infection. More than 50% of infections are caused by coagulase
      negative staphylococci and anaerobic bacteria. To avoid sepsis it is imperative
      to employ adequate high-dosage antibiotics, revisional surgery and, if necessary,
      even excision arthroplasty. There is no "ideal" anesthesiological method for
      total hip replacement. Regional techniques as well as general anesthesia have
      their specific pros and cons which are controversially discussed in respect of
      their priority. To achieve early diagnosis of embolism, especially in the case of
      high risk patients, the exigency of extensive haemodynamic monitoring as well as
      Doppler-ultrasound is discussed.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7819465
TI  - [60 years thiopental].
AB  - In 1994, thiopentone has been in clinical use as an induction agent for 60 years.
      For this reason, a literature review is given dealing with its chemical
      properties and pharmacokinetics with special regard to plasma protein binding,
      recommended speed of injection, diaplacentar transfer to the foetus in Caesarean
      section and the transfer to breast milk. The pharmacodynamics of thiopentone are
      reviewed with emphasis on the effects on the CNS, the cardiovascular system, the
      respiratory system, renal function, liver and the effect in porphyria. Its side
      effects such as local reactions and release of histamine are also reviewed. The
      clinical importance of thiopentone in anaesthesia induction and the present state
      of cerebral protection are discussed, as well as the results of controlled trials
      comparing thiopentone to other induction drugs. Thiopentone has the main
      disadvantage of a slow elimination resulting in minor CNS depression, which seems
      of very limited clinical importance. In most respects thiopentone seems to be
      comparable to its younger competitors.

PMID- 7819466
TI  - [Effects of propofol and fentanyl on the baroreceptor reflex in geriatric
      patients].
AB  - OBJECTIVE: Increasing age and anaesthetics diminish the baroreflex response to
      acute changes in blood pressure. This study was designed to investigate the
      effects of propofol and the combination of propofol with fentanyl on the
      baroreflex activity in geriatric patients. METHODS: Baroreflex sensitivity was
      studied by the method of Smyth et al. in 10 elderly (72 +/- 6 yrs) and in 10
      younger (48 +/- 6 yrs) patients. Nitroprusside (depressor test) and phenylephrine
      (pressor test) were used to induce changes in blood pressure of 20 mmHg each to
      alter the stimulation of the baroreceptor sites. Anaesthesia was induced with
      propofol, 2 mg x kg-1 b.w.m, and maintained by a continuous infusion of 12 mg x
      kg-1 x h-1 for 10 min and thereafter with 6 mg x kg-1 x h-1. Then a bolus of
      fentanyl, 7 micrograms x kg-1 b.w. was injected. Haemodynamic parameters and
      baroreflex activity were measured in the awake state, 10 min after induction of
      anaesthesia and 10 min after the administration of fentanyl. Plasma propofol
      concentrations were determined by HPLC 10 min after induction of anaesthesia with
      propofol and 10 min after injection of fentanyl. The slope of the linear
      regression changes in RR-interval [ms] per changes in systolic pressure [mmHg]
      was used as an index of the baroreflex sensitivity. RESULTS: In the awake state
      the depressor slopes were significantly reduced by 60% in the elderly patients
      when compared to the younger patients. In both groups propofol decreased reflex
      sensitivity by 38% and 41% respectively; this effect was enhanced by the addition
      of fentanyl in the younger patients, while there was no further effect in the
      elderly. The pressor slopes did not change significantly in both groups neither
      with propofol nor with the combination of fentanyl, but again reflex response was
      significantly less in the elderly patients. CONCLUSION: Our data demonstrate that
      in geriatric patients the baroreflex control of heart rate already is attenuated
      in the awake state. Propofol produces a further reduction in reflex sensitivity
      to an acute decrease in blood pressure; this effect is more pronounced in elderly
      patients as compared to younger individuals. Acute changes in posture or
      circulating blood volume during propofol anaesthesia may result in greater
      cardiovascular instability in older patients due to the greater impairment of
      circulatory control mechanisms.

PMID- 7819467
TI  - [Cardiac effects of atropine in patients treated with antidepressive medication].
AB  - It is often suggested that atropine should be avoided in patients on treatment
      with tricyclic or tetracyclic antidepressants. It is feared that the strong
      anticholinergic side effects of these drugs could exaggerate the effects of
      atropine on the heart. METHODS: In a controlled prospective study, 31 patients on
      treatment with tri- or tetracyclic antidepressants were given atropine in
      incremental doses. ECG-changes and changes in heart rate were recorded and
      compared to a control group. Atropine 2 micrograms/kg was administered in 60 sec.
      intervals up to a total dose of 10 micrograms/kg. RESULTS: The patients on
      antidepressant treatment had a higher incidence of common anticholinergic side
      effects (dryness of mouth, accommodation disorders, constipation) due to the
      anticholinergic properties of the antidepressants. In addition, the basal heart
      rate of these patients was significantly higher compared to the control group
      (81/min vs. 73/min). After administration of 2 and 4 micrograms/kg of atropine
      the patients of the control group showed a 5% resp. 4% decrease in heart rate.
      26% of these patients developed conduction disturbvances. These changes could be
      explained by the parasympathetic effect of low doses of atropine. They were less
      pronounced in the patients on treatment with antidepressants. Here, only the
      administration of 2 micrograms/kg of atropine led to a 2% decrease in heart rate.
      Only 6% of these patients developed conduction disturbances. Both groups showed
      an increase in heart rate when higher doses of atropine were administered (8 and
      10 micrograms/kg). However, the increase in heart rate after administration of 10
      micrograms/kg was significantly less in the patients on antidepressant treatment
      compared to the control group (11.4% vs. 16.2%). There were no changes of blood
      pressure during these investigations. CONCLUSION: The results of this study
      suggest that the anticholinergic properties of tri- and tetracyclic
      antidepressants include an increase in basal heart rate, but do not render the
      heart more susceptible to the cardiac effects of atropine.

PMID- 7819468
TI  - [Lymphocyte subpopulations in controlled hypotension with sodium nitroprusside].
AB  - AIM: Induced hypotension is an anaesthesiological method to reduce blood loss in
      surgical patients. The aim of this study was to investigate whether induced
      hypotension with sodium nitroprusside (SNP) causes changes in lymphocyte
      subpopulations. METHODS: In a prospective randomised evaluation 30 patients
      undergoing elective oto-rhino-laryngological interventions were studied. In 15
      patients SNP was administered to reduce the mean arterial pressure to 50 mmHg.
      There was a control group of another 15 patients. Anaesthesia was induced with
      etomidate and maintained with isoflurane. At 7 a.m. on the day of operation (T1),
      10 minutes after induction of anaesthesia (T2), 60 minutes after T2 (T3, end of
      SNP-infusion), 120 minutes (T4) after T2; 180 minutes (T5) after T2, and at 7
      a.m. on the following morning (T6) blood samples were taken. A new method (whole
      blood) was used to mark 6 different lymphocyte subpopulations with monoclonal
      antibodies which were measured by flow cytometry. RESULTS: In both groups a
      significant decrease in total lymphocyte count (from 32.7 x 10(9) cells/l
      preoperatively to 13 x 10(9) cells/l the following morning in the SNP-group and
      from 31 x 10(9) cells/l to 14.2 x 10(9) cells/l the following morning in the
      control group) was observed. In the SNP-group the HLA-DR positive T-lymphocytes
      increased from 11.8% at T1 to 19.2% at T5 and 22.3% at T6. No statistically
      significant changes were found in percentage of T-, T4-, T8-, B-lymphocytes and
      natural killer cells. CONCLUSION: The increase in the percentage of activated T
      lymphocytes is possibly due to an activation of the sympatho-adrenergic system
      after sodium nitroprusside-infusion and a subsequent redistribution of these
      cells from other organs (bone marrow, spleen, lymph nodes). The cell-mediated and
      the humoral immunity are not altered by induced hypotension. In discussing this
      result, the age of the patients, the extent of the surgical trauma, the
      anaesthesiological procedure and the methodological aspects in the lymphocyte
      assay should be taken into consideration.

PMID- 7819469
TI  - [After general anesthesia at least 6 hours of food deprivation should be
      maintained--factor or fiction?].

PMID- 7819470
TI  - [For termination of anesthesia a special room is required--fact or fiction].

PMID- 7819471
TI  - [After intravenous regional anesthesia the bloodless field must be intermittently
      opened--fact or fiction?].

PMID- 7819472
TI  - [The extent of spinal anesthesia depends on the amount of he injected local
      anesthetic--fact or fiction?].

PMID- 7819473
TI  - [Ketamine is contraindicated in craniocerebral trauma--fact or fiction?].

PMID- 7819474
TI  - [Allergic reactions to muscle relaxants are a matter of chance--fact or
      fiction?].

PMID- 7819475
TI  - [In pediatric anesthesia the half-open system is safer than the half closed
      system--fact or fiction?].

PMID- 7819476
TI  - [Abducens paresis after spinal anesthesia].

PMID- 7819477
TI  - [Intraoperative thrombolysis with rt-PA in massive pulmonary embolism during
      venous thrombectomy].
AB  - In patients with deep venous thrombosis, there is a recent trend towards surgical
      thrombectomy to avoid late complications. However, up to 10% of these patients
      suffer from severe intraoperative pulmonary embolism, 30 to 40% of whom die on
      the operating table. Treatment options for massive pulmonary embolism include
      embolectomy (high mortality), transvenous thrombus fragmentation techniques, and
      thrombolytic therapy. However, while thrombolysis is recommended as the treatment
      of choice for PTE, it is usually considered contraindicated in surgical patients
      because of bleeding complications. We report on 5 cases of severe pulmonary
      thromboembolism with marked cardiogenic shock during venous thrombectomy. Three
      patients were treated successfully by intraoperative thrombolysis alone or in
      combination with mechanical fragmentation of the embolus using a catheter
      technique under fluoroscopy (one case). Diagnosis was established by a sudden
      decrease of mean arterial pressure (from 83 to 45 mmHg), a marked increase of
      mean pulmonary artery pressure (MPAP) (from 16 to 43 mmHg), hypoxaemia (SaO2 <
      90%), an increased arterial-to-end-tidal CO2-difference (from 7 to 42 mmHg),
      and/or pulmonary angiography (2 cases). All patients had to be treated with high
      dosages of catecholamines (norepinephrine 0.5 microgram.kg-1.min-1 or epinephrine
      0.1 microgram.kg-1.min-1, and dopamine 6-15 micrograms.kg-1.min-1). Three
      patients required CPR prior to or during thrombolytic therapy. Thrombolysis was
      started intraoperatively with rt-PA with dosages ranging from 20 to 90 mg,
      applied in single injections (5-75 mg) followed by infusions (5 or 10 mg.h-1) for
      up to 8 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7819478
TI  - [Mechanical recanalization and local thrombolysis in a patient with fulminant
      pulmonary embolism and craniocerebral trauma].
AB  - A 77-year-old female patient presenting with recurrent pulmonary embolism and
      shock had a severe craniocerebral trauma after collapsing at home 2 days before
      admission. Since systemic thrombolytic therapy appeared hazardous in this
      patient, percutaneous fragmentation and distal dispersion of the proximal
      pulmonary emboli was performed using a pigtail catheter. This procedure improved
      cardiac output immediately by 15%, whereas the mean pulmonary artery pressure
      dropped only slightly from 48 to 46 mmHg. Thereafter, a streptokinase infusion of
      100,000 IU during 1 h was instituted through the pigtail catheter into the
      pulmonary artery. 12 hours after the treatment was started, cardiac output was
      raised by 70% and mean pulmonary artery pressure was decreased from 48 to 25
      mmHg. 14 days after admission, control ventilation-perfusion scan showed a
      markedly improved pulmonary perfusion, and right heart catheterization revealed
      normal right heart pressures. The patient recovered rapidly and there was no
      evidence of recurrent pulmonary embolism 18 months later. This report
      demonstrates that a percutaneous catheter fragmentation of proximal pulmonary
      emboli combined with local intermediate-dose infusion of streptokinase may be a
      helpful therapeutic option in patients with massive pulmonary embolism in whom
      systemic thrombolytic therapy is contraindicated.

PMID- 7819479
TI  - Analyzing the structure of polypeptides in membranes by fluorescence quenching.

PMID- 7819480
TI  - A liquid crystalline phase in spermidine-condensed DNA.
AB  - Over a large range of salt and spermidine concentrations, short DNA fragments
      precipitated by spermidine (a polyamine) sediment in a pellet from a dilute
      isotropic supernatant. We report here that the DNA-condensed phase consists of a
      cholesteric liquid crystal in equilibrium with a more concentrated phase. These
      results are discussed according to Flory's theory for the ordering of rigid
      polymers. The liquid crystal described here corresponds to an ordering in the
      presence of attractive interactions, in contrast with classical liquid
      crystalline DNA. Polyamines are often used in vitro to study the functional
      properties of DNA. We suggest that the existence of a liquid crystalline state in
      spermidine-condensed DNA is relevant to these studies.

PMID- 7819481
TI  - Role of substrate inhibition kinetics in enzymatic chemical oscillations.
AB  - Two chemical kinetic models are investigated using standard nonlinear dynamics
      techniques to determine the conditions under which substrate inhibition kinetics
      can lead to oscillations. The first model is a classical substrate inhibition
      scheme based on Michaelis-Menten kinetics and involves a single substrate. Only
      when this reaction takes place in a flow reactor (i.e., both substrate and
      product are taken to follow reversible flow terms) are oscillations observed;
      however, the range of parameter values over which such oscillations occur is so
      narrow it is experimentally unobservable. A second model based on a general
      mechanism applied to the kinetics of many pH-dependent enzymes is also studied.
      This second model includes both substrate inhibition kinetics as well as
      autocatalysis through the activation of the enzyme by hydrogen ion. We find that
      it is the autocatalysis that is always responsible for oscillatory behavior in
      this scheme. The substrate inhibition terms affect the steady-state behavior but
      do not lead to oscillations unless product inhibition or multiple substrates are
      present; this is a general conclusion we can draw from our studies of both the
      classical substrate inhibition scheme and the pH-dependent enzyme mechanism.
      Finally, an analysis of the nullclines for these two models allows us to prove
      that the nullcline slopes must have a negative value for oscillatory behavior to
      exist; this proof can explain our results. From our analysis, we conclude with a
      brief discussion of other enzymes that might be expected to produce oscillatory
      behavior based on a pH-dependent substrate inhibition mechanism.

PMID- 7819482
TI  - Stochastic simulation of activation in the G-protein cascade of
      phototransduction.
AB  - Activation of the G-protein cascade underlying phototransduction has been modeled
      by simulating the two-dimensional diffusional interactions that occur at the rod
      disc membrane between the three reacting protein species, which are the activated
      rhodopsin (R*), the G-protein (G), and the effector protein (E, the
      phosphodiesterase, PDE). The stochastic simulations confirm the main predictions
      of a simplified analytical model (Lamb, T. D., and E. N. Pugh, 1992, Journal of
      Physiology 449:719-758), and extend that treatment to more complicated cases,
      where there is a finite probability of reaction or a finite time for reaction.
      The simulations also provide quantitative estimates of the efficiency of coupling
      from activated G-protein (G*) to activated effector (E*) in terms of the
      concentrations, lateral diffusion coefficients, and binding rate constants of the
      participating molecules; the efficiency of coupling from G* to E* is found to be
      not as high as in the previous simplified analytical theory. The findings can be
      extended to other G-protein cascades, provided that the physical parameters of
      those cascades are specified.

PMID- 7819483
TI  - Charge displacements in a single potassium ion channel macromolecule during
      gating.
AB  - Single ion channel currents can only provide indirect information on channel
      molecular events (except for timing). In contrast, the electric displacement
      currents associated with channel gating, termed gating currents, can provide
      direct information regarding the channel molecule's conformational changes.
      However, thus far gating currents have been measured only from ensembles of
      numerous stochastically activated channels and therefore the information they
      provide is limited. This work presents, for the first time, measurements of
      gating currents from a single channel molecule. Averaging close to 8000 pre-open
      currents, aligned to the single channel opening time, enabled the detection of
      single channel gating currents with a resolution of 2 electron charges. The
      measured charge displacements show: 1) a slow component, approximately 2 fA above
      baseline level, assumed to represent stochastic conformational changes, and 2)
      transients, the most significant of which occur 1.1 and 0.3 ms before channel
      opening. The transients most likely represent apparent deterministic stages in
      the gating process. The largest transient current peak was 5.1 +/- 1.6 fA and the
      total equivalent charge transported across the membrane was 4.7 +/- 2.5 electron
      charges. This data is unique also in that it presents monitoring of the behavior
      of a single, well-defined macromolecule.

PMID- 7819484
TI  - Gating of the native and purified cardiac SR Ca(2+)-release channel with
      monovalent cations as permeant species.
AB  - The primary aim of this study was to characterize the steady-state gating of the
      native and the purified cardiac sarcoplasmic reticulum Ca(2+)-release channel
      using monovalent cations (K+ in the purified, Cs+ in the native) rather than Ca2+
      as the permeant ions. The improved resolution of the single-channel events under
      these conditions has provided a more detailed and accurate description of channel
      gating than was previously possible. Micromolar cytosolic Ca2+ activates the
      channel but in the absence of other activating ligands cannot fully open the
      channel. The relationship between the open probability (Po) and cytosolic free
      [Ca2+] in both native and purified channels indicates the binding of at least
      three Ca2+ ions for maximal activation. Lifetime analysis indicates a minimum of
      three open and five closed states for channels activated solely by Ca2+ and
      demonstrates that the primary mechanism for the increase in Po is an increase in
      the frequency of channel opening. Burst analysis also indicates that Ca2+
      activates the channel by binding to closed states of the channel to increase the
      frequency of channel opening. Correlations between successive lifetimes suggest
      the existence of at least two pathways between the open and closed states. At a
      given activating [Ca2+], the Po is lower at negative than at positive holding
      potentials; however, we find no change in the mechanisms of Ca2+ activation at
      different voltages. Po measurements and lifetime analysis indicate that the
      gating of the purified channel when activated by Ca2+ is indistinguishable from
      that of the native channel and indicate that the channels are not modified by the
      purification procedure.

PMID- 7819485
TI  - Voltage dependence of Na-Ca exchanger conformational currents.
AB  - Properties of a transient current (Icont) believed to reflect a conformational
      change of the Na-Ca exchanger molecules after Ca2+ binding were investigated.
      Intracellular Ca2+ concentration jumps in isolated cardiac myocytes were
      generated with flash photolysis of caged Ca2+ dimethoxynitrophenamine, and
      membrane currents were simultaneously measured using the whole-cell variant of
      the patch-clamp technique. A previously unresolved shallow voltage dependence of
      Icont was revealed after developing an experimental protocol designed to
      compensate for the photoconsumption of the caged compound. This voltage
      dependence can be interpreted to reflect the distribution of Na-Ca exchanger
      conformational states with the Ca2+ binding site exposed to the inside of the
      cell immediately before the flash. Analysis performed by fitting a Boltzmann
      distribution to the observed data suggests that under control conditions most
      exchanger molecules reside in states with the Ca2+ binding site facing the
      outside of the cell. Dialysis of the cytosol with 3',4'-dichlorobenzamil, an
      organic inhibitor of the Na-Ca exchange, increased the magnitude of Icont and
      changed the voltage dependence, consistent with a parallel shift of the
      charge/voltage curve. This shift may result from intracellular DCB interfering
      with an Na(+)-binding or Na(+)-translocating step. These observations are
      consistent with Icont arising from a charge movement mediated by the Na-Ca
      exchanger molecules after binding of Ca2+.

PMID- 7819487
TI  - Effect of charged residue substitutions on the thermodynamics of signal peptide
      lipid interactions for the Escherichia coli LamB signal sequence.
AB  - We have used tryptophan fluorescence spectroscopy to characterize the binding
      affinities of an Escherichia coli LamB signal peptide family for lipid vesicles.
      These peptides harbor charged residue substitutions in the hydrophobic core
      region. Titrations of peptides with vesicles composed of 1-palmitoyl-2-oleoyl-sn
      glycero-3-phosphoethanolamine and 1-palmitoyl-2-oleoyl-sn-3-phosphoglycerol
      (65:35 mol%), in conjunction with evaluation of peptide dissociation rates from
      these vesicles, were used to determine binding parameters quantitatively. We find
      that under low ionic strength conditions, point mutations introducing negatively
      charged aspartate residues substantially reduce peptide affinity relative to the
      wild-type peptide. However, the difference between wild-type and mutant peptide
      affinities was much lower under approximately physiological ionic strength. In
      addition, the lipid affinities of model surface-binding and transmembrane
      peptides were determined. These comparative studies with signal and model
      peptides permitted semi-quantitative deconvolution of signal peptide binding into
      electrostatic and hydrophobic components. We find that both interactions
      contribute significantly to binding, although the theoretically available
      hydrophobic free energy is largely offset by unfavorable polar-group effects. The
      implications of these results for understanding the potential roles of the signal
      sequence in protein translocation are discussed.

PMID- 7819486
TI  - Effect of charged residue substitutions on the membrane-interactive properties of
      signal sequences of the Escherichia coli LamB protein.
AB  - Although the central role of the signal sequence in protein export is well
      established, the molecular details underlying signal sequence in vivo function
      remain unclear. As part of our continuing effort to relate signal sequence
      phenotypes to specific biophysical properties, we have carried out an extensive
      characterization of the secondary structure and lipid interactions for a family
      of peptides corresponding to the wild-type E. coli LamB signal sequence, and
      mutants that harbor charged residue point mutations in the hydrophobic core
      region. We used membrane-resident fluorescence quenching according to the
      parallax method to determine the relative depth of insertion of tryptophan
      labeled analogs of these peptides into the acyl chain region of bilayer vesicles
      composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine and 1-palmitoyl
      2-oleoyl-sn-glycero-3-phosphoglycerol. Also, restriction of acyl chain motion
      upon peptide binding was evaluated using steady-state fluorescence anisotropy of
      1,6-diphenyl-1,3,5-hexatriene. Each of these peptides showed evidence of
      insertion into the acyl chain region, although most likely not in a transmembrane
      orientation. The mutant peptides were shown to have a reduced insertion potential
      relative to the wild-type peptide. Furthermore, tryptophan spectral properties
      indicated that insertion of the wild-type and mutant peptides enhances bilayer
      hydration. This effect was particularly pronounced with peptides harboring
      negatively charged aspartate point substitutions. The results are discussed in
      relation to the potential roles of signal sequences in mediating protein
      translocation.

PMID- 7819489
TI  - Mechanically facilitated cell-cell electrofusion.
AB  - Apparatus and methods were developed to enable mechanically facilitated cell-cell
      electrofusion to be performed. The apparatus and methods mechanically place cells
      in contact before fusion. The key component of this fusion system was a newly
      developed fusion chamber. The chamber was composed of two functionally identical
      electrodes that were housed in a multi-layer structure. The layers functioned as
      support for the electrodes. They also allowed adjustment of the distance between
      opposing electrode faces. The electrodes were constructed in a manner that
      allowed cells to be deposited, by vacuum, onto each face. Electrode faces were
      positioned at a predetermined distance from each other to mechanically force cell
      cell contact between the deposited cells. Fusion was induced by delivering direct
      current pulses to the juxtaposed cells. Fusion products were detected and
      quantitated by flow cytometry. Details of the chamber design and a protocol for
      using the fusion chamber are given. Mechanically facilitated cell-cell
      electrofusion was demonstrated by using the chamber to produce fusion products
      from like fusion partners. The practical applicability of the chamber was
      demonstrated by fusing unlike cell types. Mechanically facilitated cell-cell
      electrofusion is not specific to the cells used in this study; the chamber can be
      adapted for use with other cell types.

PMID- 7819488
TI  - Models of stratum corneum intercellular membranes: 2H NMR of macroscopically
      oriented multilayers.
AB  - Deuterium NMR was used to characterize model membrane systems approximating the
      composition of the intercellular lipid lamellae of mammalian stratum corneum
      (SC). The SC models, equimolar mixtures of ceramide:cholesterol:palmitic acid
      (CER:CHOL:PA) at pH 5.2, were contrasted with the sphingomyelin:CHOL:PA
      (SPM:CHOL:PA) system, where the SPM differs from the CER only in the presence of
      a phosphocholine headgroup. The lipids were prepared both as oriented samples and
      as multilamellar dispersions, and contained either perdeuterated palmitic acid
      (PA-d31) or [2,2,3,4,6-2H5]CHOL (CHOL-d5). SPM:CHOL:PA-d31 formed liquid-ordered
      membranes over a wide range of temperatures, with a maximum order parameter of
      approximately 0.4 at 50 degrees C for positions C3-C10 (the plateau region). The
      quadrupolar splitting at C2 was significantly smaller, suggesting an
      orientational change at this position, possibly because of hydrogen bonding with
      water and/or other surface components. A comparison of the longitudinal
      relaxation times obtained at theta = 0 degrees and 90 degrees (where theta is the
      angle between the normal to the glass plates and the magnetic field) revealed a
      significant T1Z anisotropy for all positions. In contrast to the behavior
      observed with the SPM system, lipid mixtures containing CER exhibited a complex
      polymorphism. Between 20 and 50 degrees C, a significant portion of the entire
      membrane (as monitored by both PA-d31 and CHOL-d5) was found to exist as a solid
      phase, with the remainder either a gel or liquid-ordered phase. The proportion of
      solid decreased as the temperature was increased and disappeared entirely above
      50 degrees C. Between 50 and 70 degrees C, the membrane underwent a liquid
      ordered to isotropic phase transition. These transitions were reversible but
      displayed considerable hysteresis, especially the conversion from a fluid phase
      to solid. The order profiles, relaxation behavior, and angular dependence of
      these parameters suggest strongly that both the liquid-ordered CER- and SPM
      membranes are bilayers. The unusual phase behavior observed for the CER-system,
      particularly the observation of solid-phase lipid at physiological temperatures,
      may provide insight into the functioning of the permeability barrier of stratum
      corneum.

PMID- 7819490
TI  - Contribution of electrogenic ion transport to impedance of the algae Valonia
      utricularis and artificial membranes.
AB  - The cell membrane of Valonia utricularis contains an electrogenic carrier system
      for chloride (Wang et al., Biophys J. 59:235-248 (1991)). The electrical
      impedance of V. utricularis was measured in the frequency range between 1 Hz and
      50 kHz. The analysis of the impedance spectra from V. utricularis and its
      comparison with equivalent circuit models showed that the transport system
      created a characteristic contribution to the impedance in the frequency range
      between 10 Hz and 5 kHz. The fit of the impedance spectra with the formalism
      derived from the theory of carrier-mediated transport allowed the determination
      of the kinetic parameters of chloride transport through the cell membrane of V.
      utricularis, and its passive electrical properties. Simultaneous measurements of
      the kinetic parameters with the charge pulse method demonstrated the equivalence
      of both experimental approaches with respect to the evaluation of the
      translocation rate constants of the free and the charged carriers and the total
      density of carriers within the membrane. Moreover, the impedance spectra of the
      protonophor-mediated proton transport by FCCP (carbonylcyanide p
      trifluoromethoxyphenyl-hydrazone) were measured in model membranes. The carrier
      system made a substantial contribution to the impedance of the artificial
      membranes. The analysis of the spectra in terms of a simple carrier system (Benz
      and McLaughlin, 1983, Biophys. J. 41:381-398) allowed the evaluation of the
      kinetic and equilibrium parameters of the FCCP-mediated proton transport. The
      possible application of the measurement of impedance spectra for the study of
      biological transport systems is discussed.

PMID- 7819491
TI  - The temperature-composition phase diagram and mesophase structure
      characterization of monopentadecenoin in water.
AB  - The temperature-composition phase diagram of monopentadecenoin, a
      monoacylglycerol with a cis monounsaturated fatty acid 15 carbon atoms long
      (C15:1c10) in water was constructed using x-ray diffraction. Low- and wide-angle
      diffraction patterns were collected from samples of fixed hydration as a function
      of temperature in the heating direction on x-ray-sensitive film. The temperature
      and hydration ranges investigated were 0-104 degrees C and 0-60% (w/w) water,
      respectively. The phases identified in the system include the lamellar
      crystalline phase, the lamellar liquid crystalline phase, the fluid isotropic
      phase, and two inverted cubic phases belonging to space groups la3d (Q230) and
      Pn3m (Q244). Particular attention has been devoted to the issues of phase
      equilibrium, phase boundary verification, and structure characterization. The
      phase diagrams of monopentadecenoin, monomyristolein (C14:1c9), and monoolein
      (C18:1c9) are compared, and the impact of molecular structure on mesophase
      stability and structure is discussed.

PMID- 7819492
TI  - Bending, hydration and interstitial energies quantitatively account for the
      hexagonal-lamellar-hexagonal reentrant phase transition in
      dioleoylphosphatidylethanolamine.
AB  - We have accounted for the unusual structural change wherein
      dioleoylphosphatidylethanolamine undergoes a hexagonal-lamellar-hexagonal
      transition sequence as the water content is reduced systematically. We describe
      the role played by the energies of bending, hydration, voids in hexagonal
      interstices, and van der Waals interaction in this transition sequence. We have
      used the X-ray diffraction and osmotic stress experiments on the two phases to
      derive the structural parameters and all of the force constants defining the
      energetics of the hexagonal and lamellar phases. We have calculated the chemical
      potentials of lipid and water in both phases and derived the phase diagram of the
      lipid with no free, adjustable parameters. The calculated temperature/osmotic
      stress and temperature/composition diagrams quantitatively agree with experiment.
      The reentrant transition appears to be driven by a delicate balance between the
      hydration energy in the lamellar phase and bending energy in the hexagonal phase,
      whereas the energy of voids in hexagonal interstices defines its energy scale and
      temperature range. Van der Waals attraction between the bilayers in the lamellar
      phase does not appear to be important in this transition.

PMID- 7819493
TI  - Unfixed cryosections of striated muscle to study dynamic molecular events.
AB  - The structures of the actin and myosin filaments of striated muscle have been
      studied extensively in the past by sectioning of fixed specimens. However,
      chemical fixation alters molecular details and prevents biochemically induced
      structural changes. To overcome these problems, we investigate here the potential
      of cryosectioning unfixed muscle. In cryosections of relaxed, unfixed specimens,
      individual myosin filaments displayed the characteristic helical organization of
      detached cross-bridges, but the filament lattice had disintegrated. To preserve
      both the filament lattice and the molecular structure of the filaments, we
      decided to section unfixed rigor muscle, stabilized by actomyosin cross-bridges.
      The best sections showed periodic, angled cross-bridges attached to actin and
      their Fourier transforms displayed layer lines similar to those in x-ray
      diffraction patterns of rigor muscle. To preserve relaxed filaments in their
      original lattice, unfixed sections of rigor muscle were picked up on a grid and
      relaxed before negative staining. The myosin and actin filaments showed the
      characteristic helical arrangements of detached cross-bridges and actin subunits,
      and Fourier transforms were similar to x-ray patterns of relaxed muscle. We
      conclude that the rigor structure of muscle and the ability of the filament
      lattice to undergo the rigor-relaxed transformation can be preserved in unfixed
      cryosections. In the future, it should be possible to carry out dynamic studies
      of active sacromeres by cryo-electron microscopy.

PMID- 7819494
TI  - Oblique section 3-D reconstruction of relaxed insect flight muscle reveals the
      cross-bridge lattice in helical registration.
AB  - In this work we examined the arrangement of cross-bridges on the surface of
      myosin filaments in the A-band of Lethocerus flight muscle. Muscle fibers were
      fixed using the tannic-acid-uranyl-acetate, ("TAURAC") procedure. This new
      procedure provides remarkably good preservation of native features in relaxed
      insect flight muscle. We computed 3-D reconstructions from single images of
      oblique transverse sections. The reconstructions reveal a square profile of the
      averaged myosin filaments in cross section view, resulting from the symmetrical
      arrangement of four pairs of myosin heads in each 14.5-nm repeat along the
      filament. The square profiles form a very regular right-handed helical
      arrangement along the surface of the myosin filament. Furthermore, TAURAC
      fixation traps a near complete 38.7 nm labeling of the thin filaments in relaxed
      muscle marking the left-handed helix of actin targets surrounding the thick
      filaments. These features observed in an averaged reconstruction encompassing
      nearly an entire myofibril indicate that the myosin heads, even in relaxed
      muscle, are in excellent helical register in the A-band.

PMID- 7819495
TI  - A spin label that binds to myosin heads in muscle fibers with its principal axis
      parallel to the fiber axis.
AB  - We have used an indane-dione spin label (2-[-oxyl-2,2,5,5-tetramethyl-3-pyrrolin
      3-yl)methenyl]in dane-1,3-dione), designated InVSL, to study the orientation of
      myosin heads in bundles of chemically skinned rabbit psoas muscle fibers, with
      electron paramagnetic resonance (EPR) spectroscopy. After reversible preblocking
      with 5,5'-dithiobis(2-nitro-benzoic acid) (DTNB), we were able to attach most of
      the spin label covalently and rigidly to either Cys 707 (SH1) or Cys 697 (SH2) on
      myosin heads. EPR spectra of labeled fibers contained substantial contributions
      from both oriented and disordered populations of spin labels. Similar spectra
      were obtained from fibers decorated with InVSL-labeled myosin heads (subfragment
      1), indicating that virtually all the spin labels in labeled fibers are on the
      myosin head. We specifically labeled SH2 with InVSL after reversible preblocking
      of the SH1 sites with 1-fluoro-2,4-dinitrobenzene (FDNB), resulting in a spectrum
      that indicated only disordered spin labels. Therefore, the oriented and
      disordered populations correspond to labels on SH1 and SH2, respectively. The
      spectrum of SH2-bound labels was subtracted to produce a spectrum corresponding
      to SH1-bound labels, which was used for further analysis. For this corrected
      spectrum, the angle between the fiber axis and the principal axis of the spin
      label was fitted well by a Gaussian distribution centered at theta o = 11 +/- 1
      degree, with a full width at half-maximum of delta theta = 15 +/- 2 degrees. The
      unique orientation of InVSL, with its principal axis almost parallel to the fiber
      axis, makes it complementary to spin labels previously studied in this system.
      This label can provide unambiguous information about axial rotations of myosin
      heads, since any axial rotation of the head must be reflected in the same axial
      rotation of the principal axis of the probe, thus changing the hyperfine
      splitting. Therefore, InVSL-labeled fibers have ideal properties needed for
      further exploration myosin head orientation and rotational motion in muscle.

PMID- 7819496
TI  - Protein and acidosis alter calcium-binding and fluorescence spectra of the
      calcium indicator indo-1.
AB  - The fluorescent indicator indo-1 is widely used to monitor intracellular calcium
      concentration. However, quantitation is limited by uncertain effects of the
      intracellular environment on indicator properties. The goal of this study was to
      determine the effects of protein and acidosis on the fluorescence spectra and
      calcium dissociation constant (Kd) of indo-1. With 350 nm excitation light, the
      ratio of indo-1 fluorescence in the absence versus the presence of saturating
      Ca2+ at wavelength lambda (S lambda) and Kd increased with [protein]. At pH 7.3,
      Kd, S400, and S470, which were 210 nM, 0.033, and 1.433 in the absence of
      protein, increased to 808 nM, 0.161, and 2.641, respectively, by adding proteins
      from frog muscle and to 638 nM, 0.304, and 3.039, respectively, by adding
      proteins from rat heart. Effects of protein on indo-1 fluorescence were reduced
      at higher [indo-1]. Acidosis (pH 6.3) had separate effects, which were additive
      to those of protein: in the absence of protein, acidosis increased Kd to 640 nM;
      frog muscle proteins further increased Kd to 1700 nM. Acidosis also changed S
      lambda slightly. In summary, interaction with protein or protons alters indo-1
      calcium-binding and fluorescence. These findings are consistent with several
      previous studies and suggest that indo-1 calibration constants need to be derived
      in the presence of appropriate types of protein, ratio of [indo-1]/[protein], and
      pH.

PMID- 7819497
TI  - Kinetic and thermodynamic studies of the cross-bridge cycle in rabbit psoas
      muscle fibers.
AB  - The effect of temperature on elementary steps of the cross-bridge cycle was
      investigated with sinusoidal analysis technique in skinned rabbit psoas fibers.
      We studied the effect of MgATP on exponential process (C) to characterize the
      MgATP binding step and cross-bridge detachment step at six different temperatures
      in the range 5-30 degrees C. Similarly, we studied the effect of MgADP on
      exponential process (C) to characterize the MgADP binding step. We also studied
      the effect of phosphate (Pi) on exponential process (B) to characterize the force
      generation step and Pi-release step. From the results of these studies, we
      deduced the temperature dependence of the kinetic constants of the elementary
      steps and their thermodynamic properties. We found that the MgADP association
      constant (K0) and the MgATP association constant (K1) significantly decreased
      when the temperature was increased from 5 to 20 degrees C, implying that
      nucleotide binding became weaker at higher temperatures. K0 and K1 did not change
      much in the 20-30 degree C range. The association constant of Pi to cross-bridges
      (K5) did not change much with temperature. We found that Q10 for the cross-bridge
      detachment step (k2) was 2.6, and for its reversal step (k-2) was 3.0. We found
      that Q10 for the force generation step (Pi-isomerization step, k4) was 6.8, and
      its reversal step (k-4) was 1.6. The equilibrium constant of the detachment step
      (K2) was not affected much by temperature, whereas the equilibrium constant of
      the force generation step (K4) increased significantly with temperature increase.
      Thus, the force generation step consists of an endothermic reaction. The rate
      constant of the rate-limiting step (k6) did not change much with temperature,
      whereas the ATP hydrolysis rate increased significantly with temperature
      increase. We found that the force generation step accompanies a large entropy
      increase and a small free energy change; hence, this step is an entropy-driven
      reaction. These observations are consistent with the hypothesis that the
      hydrophobic interaction between residues of actin and myosin underlies the
      mechanism of force generation. We conclude that the force generation step is the
      most temperature-sensitive step among elementary steps of the cross-bridge cycle,
      which explains increased isometric tension at high temperatures in rabbit psoas
      fibers.

PMID- 7819498
TI  - A program for developing a comprehensive mathematical description of the
      crossbridge cycle of muscle.
AB  - We describe a computer modeling system for determining the changes of force,
      fraction of attached crossbridges, and crossbridge flux rate through a
      specifiable transition in response to length changes imposed on a crossbridge
      model of muscle. The crossbridge cycle is divided into multiple attached and
      detached states. The rates of transition from one state to another are defined by
      rate coefficients that can either be constant or vary with the position of the
      crossbridge relative to the thin-filament attachment site. This scheme leads to a
      system of differential equations defining the rates of change for the fractions
      of bridges in each state. Solutions for this system of equations are obtained at
      specified times during and after a length change using a method for systems with
      widely varying time constants (C. W. Gear, 1971, Numerical Initial Value Problems
      in Ordinary Differential Equations, Prentice-Hall, Englewood Cliffs, NJ).
      Crossbridges are divided into discrete populations that differ both in their
      axial displacement with respect to thin filament attachment sites and with
      respect to the twist of the actin helix. Separate solutions are made for the
      individual populations and are then averaged to obtain the ensemble response.
      Force is determined as the sum of the product of the force associated with each
      state multiplied by the fraction of bridges in that state. A measure of metabolic
      rate is determined as the net flux through one of the crossbridge transitions.
      When the force-extension characteristics of the individual crossbridges are
      linear and the filaments are noncompliant the fraction of attached bridges is
      equivalent to sarcomere stiffness. To illustrate the operation of the program, we
      also describe here some results obtained with a simplified scheme.

PMID- 7819499
TI  - Condensation of supercoiled DNA induced by MnCl2.
AB  - Multivalent cations condense DNA in vitro, but it had been thought that a valence
      of at least + 3 was required in aqueous solution. We have found that Mn2+ can
      produce toroidal condensates of supercoiled plasmid DNA, but not of linearized
      plasmid. Mg2+ does not cause condensation, and neither MgCl2 nor NaCl can negate
      the effect of MnCl2, indicating that the condensation mechanism with Mn is not
      primarily electrostatic. Supercoiled MnDNA is more extensively digested than the
      linear form by S1 nuclease. Supercoiling appears to cooperate with Mn2+ in
      stabilizing helix distortions and also provides a "pressure" that enhances
      lateral association.

PMID- 7819500
TI  - Inversion of proton translocation in bacteriorhodopsin mutants D85N, D85T, and
      D85,96N.
AB  - Proton translocation activity of bacteriorhodopsin mutants lacking the proton
      acceptor Asp-85 was investigated using the black lipid membrane technique.
      Mutants D85N, D85T, and D85,96N were constructed and homologously expressed in
      Halobacterium salinarium to yield a membrane fraction with a buoyant density of
      1.18 g/cm3, i.e., identical to that of wild-type purple membrane. In all mutants,
      the absorbance maximum was red-shifted between 27 and 49 nm compared with wild
      type, and the pKa values of the respective Schiff bases were reduced to between
      8.3 and 8.9 compared with the value of > 13 in wild type. Therefore, a mixture of
      chromophores absorbing at 410 nm (deprotonated form) and around 600 nm
      (protonated form) exists at physiological pH. In continuous blue light, the
      deprotonated form generates stationary photocurrents. The currents are enhanced
      by a factor of up to 50 upon addition of azide in D85N and D85,96N mutants,
      whereas D85T shows no azide effect. The direction of these currents is the same
      as in wild type in yellow light. Yellow light alone is not sufficient to generate
      stationary currents in the mutants, but increasing yellow light intensity in the
      presence of blue light leads to an inversion of the current. Because all currents
      are carried by protons, this two-photon process demonstrates an inverted proton
      translocation by BR mutants.

PMID- 7819501
TI  - Measurement and global analysis of the absorbance changes in the photocycle of
      the photoactive yellow protein from Ectothiorhodospira halophila.
AB  - The photocycle of the photoactive yellow protein (PYP) from Ectothiorhodospira
      halophila was examined by time-resolved difference absorption spectroscopy in the
      wavelength range of 300-600 nm. Both time-gated spectra and single wavelength
      traces were measured. Global analysis of the data established that in the time
      domain between 5 ns and 2 s only two intermediates are involved in the room
      temperature photocycle of PYP, as has been proposed before (Meyer T.E., E.
      Yakali, M. A. Cusanovich, and G. Tollin. 1987. Biochemistry. 26:418-423; Meyer,
      T. E., G. Tollin, T. P. Causgrove, P. Cheng, and R. E. Blankenship. 1991.
      Biophys. J. 59:988-991). The first, red-shifted intermediate decays
      biexponentially (60% with tau = 0.25 ms and 40% with tau = 1.2 ms) to a blue
      shifted intermediate. The last step of the photocycle is the biexponential (93%
      with tau = 0.15 s and 7% with tau = 2.0 s) recovery to the ground state of the
      protein. Reconstruction of the absolute spectra of these photointermediates
      yielded absorbance maxima of about 465 and 355 nm for the red- and blue-shifted
      intermediate with an epsilon max at about 50% and 40% relative to the epsilon max
      of the ground state. The quantitative analysis of the photocycle in PYP described
      here paves the way to a detailed biophysical analysis of the processes occurring
      in this photoreceptor molecule.

PMID- 7819502
TI  - pH-induced structural changes in bacteriorhodopsin studied by Fourier transform
      infrared spectroscopy.
AB  - Previous C13-NMR studies showed that two of the four internal aspartic acid
      residues (Asp-96 and Asp-115) of bacteriorhodopsin (bR) are protonated up to pH =
      10, but no accurate pKa of these residues has been determined. In this work,
      infrared spectroscopy with the attenuated total reflection technique was used to
      characterize pH-dependent structural changes of ground-state, dark-adapted wild
      type bacteriorhodopsin and its mutant (D96N) with aspartic acid-96 replaced by
      asparagine. Data indicated deprotonation of Asp-96 at high pH (pKa = 11.4 +/-
      0.1), but no Asp-115 titration was observed. The analysis of the whole spectral
      region characteristic to complex conformational changes in the protein showed a
      more complicated titration with an additional pKa value (pKa1 = 9.3 +/- 0.3 and
      pKa2 = 11.5 +/- 0.2). Comparison of results obtained for bR and the D96N mutant
      of bR shows that the pKa approximately 11.5 characterizes not a direct titration
      of Asp-96 but a protein conformational change that makes Asp-96 accessible to the
      external medium.

PMID- 7819503
TI  - Stereodynamic properties of the cooperative homodimeric Scapharca inaequivalvis
      hemoglobin studied through optical absorption spectroscopy and ligand rebinding
      kinetics.
AB  - The study of the thermal evolution of the Soret band in heme proteins has proved
      to be a useful tool to understand their stereodynamic properties; moreover, it
      enables one to relate protein matrix fluctuations and functional behavior when
      carried out in combination with kinetic experiments on carbon monoxide rebinding
      after flash photolysis. In this work, we report the thermal evolution of the
      Soret band of deoxy, carbonmonoxy, and nitric oxide derivatives of the
      cooperative homodimeric Scapharca inaequivalvis hemoglobin in the temperature
      range 10-300 K and the carbon monoxide rebinding kinetics after flash photolysis
      in the temperature range 60-200 K. The two sets of results indicate that
      Scapharca hemoglobin has a very rigid protein structure compared with other
      hemeproteins. This feature is brought out i) by the absence of nonharmonic
      contributions to the soft modes coupled to the Soret band in the liganded
      derivatives, and ii) by the almost "in plane" position of the iron atom in the
      photoproduct obtained approximately 10(-8) s after dissociating the bound carbon
      monoxide molecule at 15 K.

PMID- 7819504
TI  - Calorimetric study of crystal growth of ice in hydrated methemoglobin and of
      redistribution of the water clusters formed on melting the ice.
AB  - Calorimetric studies of the melting patterns of ice in hydrated methemoglobin
      powders containing between 0.43 and 0.58 (g water)/(g protein), and of their
      dependence on annealing at subzero temperatures and on isothermal treatment at
      ambient temperature are reported. Cooling rates were varied between approximately
      1500 and 5 K min-1 and heating rate was 30 K min-1. Recrystallization of ice
      during annealing is observed at T > 228 K. The melting patterns of annealed
      samples are characteristically different from those of unannealed samples by the
      shifting of the melting temperature of the recrystallized ice fraction to higher
      temperatures toward the value of "bulk" ice. The "large" ice crystals formed
      during recrystallization melt on heating into "large" clusters of water whose
      redistribution and apparent equilibration is followed as a function of time
      and/or temperature by comparison with melting endotherms. We have also studied
      the effect of cooling rate on the melting pattern of ice with a methemoglobin
      sample containing 0.50 (g water)/(g protein), and we surmise that for this
      hydration cooling at rates of > or = approximately 150 K min-1 preserves on the
      whole the distribution of water molecules present at ambient temperature.

PMID- 7819505
TI  - Structural characterization of the micelle-vesicle transition in lecithin-bile
      salt solutions.
AB  - Small-angle neutron scattering (SANS) and dynamic light scattering (QLS) are used
      to characterize the aggregates found upon dilution of mixed lecithin-bile salt
      micelles. Molar ratios of lecithin (L) to taurocholate (TC) studied varied from
      0.1 to 1, and one series contained cholesterol (Ch). Mixed aggregates of L and
      taurodeoxycholate (TDC) at ratios of 0.4 and 1 were also examined. In all cases
      the micelles are cylindrical or globular and elongate upon dilution. The radius
      of the mixed micelles varies only slightly with the overall composition of
      lecithin and bile salt which indicates that the composition of the cylindrical
      micelle body is nearly constant. The transition from micelles to vesicles is a
      smooth transformation involving a region where micelles and vesicles coexist.
      SANS measurements are more sensitive to the presence of two aggregate populations
      than QLS. Beyond the coexistence region the vesicle size and degree of
      polydispersity decrease with dilution. Incorporation of a small amount of
      cholesterol in the lipid mixture does not affect the sequence of observed
      aggregate structures.

PMID- 7819507
TI  - Viscoelasticity of living cells allows high resolution imaging by tapping mode
      atomic force microscopy.
AB  - Application of atomic force microscopy (AFM) to biological objects and processes
      under physiological conditions has been hampered so far by the deformation and
      destruction of the soft biological materials invoked. Here we describe a new mode
      of operation in which the standard V-shaped silicon nitride cantilever is
      oscillated under liquid and damped by the interaction between AFM tip and sample
      surface. Because of the viscoelastic behavior of the cellular surface, cells
      effectively "harden" under such a tapping motion at high frequencies and become
      less susceptible to deformation. Images obtained in this way primarily reveal the
      surface structure of the cell. It is now possible to study physiological
      processes, such as cell growth, with a minimal level of perturbation and high
      spatial resolution (approximately 20 nm).

PMID- 7819506
TI  - Structure of corneal scar tissue: an X-ray diffraction study.
AB  - Full-thickness corneal wounds (2 mm diameter) were produced in rabbits at the
      Schepens Eye Research Institute, Boston. These wounds were allowed to heal for
      periods ranging from 3 weeks to 21 months. The scar tissue was examined using low
      and wide-angle x-ray diffraction from which average values were calculated for
      1) the center-to-center collagen fibril spacing, 2) the fibril diameter, 3) the
      collagen axial periodicity D, and 4) the intermolecular spacing within the
      collagen fibrils. Selected samples were processed for transmission electron
      microscopy. The results showed that the average spacing between collagen fibrils
      within the healing tissue remained slightly elevated after 21 months and there
      was a small increase in the fibril diameter. The collagen D-periodicity was
      unchanged. There was a significant drop in the intermolecular spacing in the scar
      tissues up to 6 weeks, but thereafter the spacing returned to normal. The first
      order equatorial reflection in the low-angle pattern was visible after 3 weeks
      and became sharper and more intense with time, suggesting that, as healing
      progressed, the number of nearest neighbor fibrils increased and the distribution
      of nearest neighbor spacings reduced. This corresponded to the fibrils becoming
      more ordered although, even after 21 months, normal packing was not achieved.
      Ultrastructural changes in collagen fibril density measured from electron
      micrographs were consistent with the increased order of fibril packing measured
      by x-ray diffraction. The results suggest that collagen molecules have a normal
      axial and lateral arrangement within the fibrils of scar tissue. The gradual
      reduction in the spread of interfibrillar spacings may be related to the
      progressive decrease in the light scattered from the tissue as the wound heals.

PMID- 7819508
TI  - Translational diffusion of bovine prothrombin fragment 1 weakly bound to
      supported planar membranes: measurement by total internal reflection with
      fluorescence pattern photobleaching recovery.
AB  - Previous work has shown that bovine prothrombin fragment 1 binds to substrate
      supported planar membranes composed of phosphatidylcholine (PC) and
      phosphatidylserine (PS) in a Ca(2+)-specific manner. The apparent equilibrium
      dissociation constant is 1-15 microM, and the average membrane residency time is
      approximately 0.25 s-1. In the present work, fluorescence pattern photobleaching
      recovery with evanescent interference patterns (TIR-FPPR) has been used to
      measure the translational diffusion coefficients of the weakly bound fragment 1.
      The results show that the translational diffusion coefficients on fluid-like
      PS/PC planar membranes are on the order of 10(-9) cm2/s and are reduced when the
      fragment 1 surface density is increased. Control measurements were carried out
      for fragment 1 on solid-like PS/PC planar membranes. The dissociation kinetics
      were similar to those on fluid-like membranes, but protein translational mobility
      was not detected. TIR-FPPR was also used to measure the diffusion coefficient of
      the fluorescent lipid NBD-PC in fluid-like PS/PC planar membranes. In these
      measurements, the diffusion coefficient was approximately 10(-8) cm2/s, which is
      consistent with that measured by conventional fluorescence pattern photobleaching
      recovery. This work represents the first measurement of a translational diffusion
      coefficient for a protein weakly bound to a membrane surface.

PMID- 7819509
TI  - The movement of spermatozoa with helical head: theoretical analysis and
      experimental results.
AB  - The present work is concerned with the study of the swimming of flagellated
      microscopic organisms with a helical head and a helical pattern of flagellar
      beating, such as Xenopus sperms. The theoretical approach is similar to that
      taken by Chang and Wu (1971) in the study of helical flagellar movement. The
      model used in the present study allows us to determine the velocity of propulsion
      (U) and the frequency of rotation of the sperm head (fh) as a function of the
      frequency of the wave of motion (ft) traveling along the tail. The results
      relative to the case of helical and planar flagellar waves are compared. Our main
      finding is that the helical shape of the head seems to increase the efficiency of
      propulsion of the spermatozoon when compared with the more commonly shaped
      spherical head. Experimentally measured values of fh versus U may be fitted by a
      linear plot whose slope is much higher than that corresponding to the case of
      planar flagellar beating. This fact is consistent with an effectively three
      dimensional (nonplanar) movement of the flagellar tail. However, the results do
      not fit those predicted from a circular helix, suggesting that a different shape
      of the flagellar beating should be considered.

PMID- 7819511
TI  - Diagnostic use of fine needle aspiration in the investigation of pancreatic
      lesions.

PMID- 7819510
TI  - Intrinsic cytosolic calcium buffering properties of single rat cardiac myocytes.
AB  - Intracellular passive Ca2+, buffering was measured in voltage-clamped rat
      ventricular myocytes. Cells were loaded with indo-1 (K+ salt) to an estimated
      cytosolic concentration of 44 +/- 5 microM (Mean +/- SEM, n = 5), and accessible
      cell volume was estimated to be 24.5 +/- 3.6 pl. Ca2+ transport by the
      sarcoplasmic reticulum (SR) Ca-ATPase and sarcolemmal Na-Ca exchange was
      inhibited by treatment with thapsigargin and Na-free solutions, respectively.
      Extracellular [Ca2+] was maintained at 10 mM and, in some experiments, the
      mitochondrial uncoupler "1799" was used to assess the degree of mitochondrial
      Ca2+ uptake. To perform single cell titrations, intracellular Ca2+ ([Ca2+]i) was
      increased progressively by a train of depolarizing voltage clamp pulses from -40
      to +10 mV. The total Ca2+ gain with each pulse was calculated by integration of
      the Ca current and then analyzed as a function of the rapid change in [Ca2+]i
      during the pulse. In the range of [Ca2+]i from 0.1 to 2 microM, overall cell
      buffering was well described as a single lumped Michaelis-Menten type species
      with an apparent dissociation constant, KD, of of 0.63 +/- 0.07 microM (n = 5)
      and a binding capacity, Bmax, of 162 +/- 15 mumol/l cell H2O. Correction for
      buffering attributable to cytosolic indo-1 gives intrinsic cytosolic Ca2+
      buffering parameters of KD = 0.96 +/- 0.18 microM and Bmax = 123 +/- 18 mumol/l
      cell H2O. The fast Ca2+ buffering measured in this manner agrees reasonably with
      the characteristics of known rapid Ca buffers (e.g., troponin C, calmodulin, and
      SR Ca-ATPase), but is only about half of the total Ca2+ buffering measured at
      equilibrium. Inclusion of slow Ca buffers such as the Ca/Mg sites on troponin C
      and myosin can account for the differences between fast Ca2+ buffering in phase
      with the Ca current measured in the present experiments and equilibrium Ca2+
      buffering. The present data indicate that a rapid rise of [Ca2+]i from 0.1 to 1
      microM during a contraction requires approximately 50 microM Ca2+ to be added to
      the cytosol.

PMID- 7819512
TI  - Immunofluorescent staining of metastatic carcinoma cells in serious fluid with
      carcinoembryonic antibody, epithelial membrane antibody, AUA-1 and Ber-EP4.
AB  - Using an indirect immunofluorescence technique, we assessed the accuracy and
      clinical usefulness of a panel of monoclonal and polyclonal antibodies. The panel
      consisted of carcinoembryonic antibody (CEA) and epithelial membrane antibody
      (EMA), AUA-1, and Ber-EP4 conjugated with fluorescein isothiocyanate. Twenty-six
      specimens from pleural, peritoneal or pericardial effusions known to contain
      carcinoma cells (adenocarcinoma or large cell anaplastic carcinoma) and 16
      specimens without carcinoma were first examined. The sensitivity and specificity
      for each of the antibodies were as follows: CEA, 71% and 75%; EMA, 96% and 81%;
      AUA-1, 80% and 100%; and Ber-EP4, 85% and 100%, respectively. The panel of
      antibodies was then applied to a group of 14 'problematic' fluids. These had been
      identified as causing dilemmas in interpretation, either because the cells in the
      fluids were of equivocal appearance on light microscopy, or the cytological
      diagnosis was different from that expected in the light of the clinical condition
      of the patient. Insufficient cellular material was present in one specimen. In
      five (39%) of the cases the immunochemical staining supported the light
      microscopic diagnosis. In four (30%) cases, however, the results indicated that
      the original light microscopic report was incorrect. Two of these were examples
      of large cell carcinoma of the lung, in which false negative reports had been
      issued on pleural fluids. The other two were cases of benign ovarian tumours in
      which a false positive report had been issued. The immunostaining also clarified
      the final diagnosis in the three patients (23%) on whom 'suspicious' cytological
      reports had previously been issued. The remaining case, fluid from a patient with
      a high grade mixed Mullerian tumour of the ovary, was unresolved. We conclude
      that immunofluorescent staining by AUA-1, EMA and Ber-EP4 is an aid in the
      cytological interpretation of serous fluids. CEA is much less helpful.

PMID- 7819513
TI  - Detection of p53 protein and Ki-67 proliferation antigen in human papillomavirus
      (HPV)-positive and HPV-negative cervical lesions by immunohistochemical double
      staining.
AB  - In HPV-associated genital lesions, low or absent expression of p53 has been
      attributed to the rapid degradation of p53 through its binding with HPV E6
      protein. In this study, we examined p53 protein expression with two antibodies
      (CM1 polyclonal and PAb 1801 monoclonal antibodies), and Ki-67 proliferation
      antigen (monoclonal antibody) using an immunohistochemical (IHC) double-staining
      technique in 77 HPV-positive cervical lesions (HPV6, HPV11, HPV16, HPV18, HPV31,
      and HPV33) and in 15 HPV-negative cases. p53 protein expression was detected in
      36/92 (39.1%) of the specimens. Of the p53-positive cases, 80.6% (29/36) were HPV
      positive samples, including 10/23 (43.5%) of HPV16- and 3/10 (30%) of HPV18
      positive biopsies. In 52.8% of the p53-positive samples, the expression was found
      in less than 5% of the basal cells which were also positive for Ki-67. Ki-67
      proliferation marker was found in 91/92 specimens, most intensely in those
      infected by HPV16. p53 was more abundant in progressive or persistent lesions,
      but no differences were found between HPV-positive and HPV-negative samples. The
      positive IHC double-staining of both p53 and Ki-67 proliferation antigen in the
      same basal (and parabasal) cells indicates that these two normal cell-cycle
      proteins are being expressed while the cells are entering from the G1 to the S
      phase of the cell cycle. Since the latter property is only attributed to the wild
      type p53 (but not to mutated p53), the p53 protein detected in HPV lesions by IHC
      is likely to be the wild-type p53 rather than mutated p53, and the result was
      also confirmed by using p53 mutant specific antibody PAb 240. Accordingly, the
      concept of HPV inactivating the wild-type p53 protein should be re-examined, and
      other mechanisms for HPV-mediated carcinogenesis should be considered.

PMID- 7819514
TI  - Evaluation of a cytological scoring system for predicting histological grade and
      disease-free survival in primary breast cancer.
AB  - A simple cytological scoring system was evaluated as a method of predicting
      histological grade and disease-free survival in 79 patients with primary breast
      cancer. The mitotic activity index and oestrogen receptor status were also
      assessed for their predictive value. The concordance between cytological scores
      and histological grades was good (80%) for low-grade lesions, but poor (45%) for
      high-grade lesions. Similar results were found using the mitotic activity index
      as a prognostic indicator. Cytological grading was not found to be an independent
      prognostic indicator after a median follow up of 8 years.

PMID- 7819515
TI  - Aspiration cytology and immunocytochemical study of an unusual carcinoma of the
      pancreas with pleomorphic giant cells.

PMID- 7819516
TI  - Papillary and solid neoplasm of the pancreas: fine needle aspiration cytology.

PMID- 7819517
TI  - Guidelines for cytology procedures and reporting on fine needle aspirates of the
      breast. Cytology Subgroup of the National Coordinating Committee for Breast
      Cancer Screening Pathology.

PMID- 7819518
TI  - The brain beyond the synapse: a review.
AB  - Several topics in contemporary neuroscience are treated in historical
      perspective. These include the localizationist-connectionist model of brain
      function and its influence on experimental neuroscience and clinical management
      of brain damaged persons; brain plasticity; the accumulating evidence for non
      synaptic diffusion neurotransmission (NDN) as a major mechanism of information
      transmission in the brain; and the co-existence of plasticity and localization as
      well as of synaptic and non-synaptic mechanisms. The status of theory in the
      neurosciences is examined.

PMID- 7819519
TI  - Changes in human respiratory sensation induced by acute high altitude hypoxia.
AB  - Respiratory sensation was studied in European low-landers at an altitude of 4382
      m after a helicopter flight in order to investigate the acute and prolonged
      effects of high altitude hypoxia. At rest the ability to detect four inspiratory
      resistive loads can be used to create a sensitivity index P(A) without taking the
      response bias (B) into account, based on the Sensory Decision Theory. In 6
      subjects respiratory sensitivity increased significantly under acute and
      prolonged hypoxia after 3-4 days of high altitude exposure. The respiratory
      sensitivity increased with the hyperventilation and mouth pressure increase
      induced by hypoxia. Hypoxia might also have feedback effects on the peripheral
      and central nervous integration of the respiratory sensation stimuli. One subject
      suffering from acute mountain sickness showed a severe decrease in his
      sensitivity index P(A) under hypoxic conditions, while the parameters of his
      cardiorespiratory function evolved in the same classical way as the other
      subjects who adapted well to altitude hypoxia. The increase in respiratory
      sensation may be the first necessary step in altitude acclimatization and might
      serve as a useful marker of this adaptation.

PMID- 7819520
TI  - Identification of short latency auditory responsive neurons in the cat dentate
      nucleus.
AB  - Intracellular recordings of activity in response to acoustic stimuli were
      obtained from units of the dentate nucleus of conscious cats. Twelve units with
      short latency responses to 70 dB clicks or hisses were injected intracellularly
      with biocytin and identified morphologically. The identified cells were small,
      relatively aspinous, multipolar cells with diameters < 20 microns. Most had
      beaded dendritic varicosities. Six were located centrally, and five were on the
      border of the nucleus. One appeared to be an axonal process. The results provide
      direct evidence that small cells of the dentate nucleus can respond with short
      latencies of 4-14 ms to acoustic stimuli. We suggest that these cells are part of
      a primary ascending auditory transmission pathway between cochlear nuclei and the
      motor cortex.

PMID- 7819521
TI  - Application of automated flow injection analysis to determine nitrite and nitrate
      in mouse brain.
AB  - Nitric oxide level in the mouse brain was estimated by determination of nitrite
      and nitrate using an automated flow injection analyser for NOx. Different
      experimental conditions were examined to determine which produced reproducible
      results. After pretreatment of tissue specimens by the ZnSO4-NaOH method for
      deproteinization, reproducible and constant values were obtained. The values were
      more accurate immediately after sectioning without freezing than after 24 h with
      freezing. Two sacrifice methods, decapitation and microwave irradiation of the
      head, were investigated, but there was no significant difference between the two.
      No substances in the mouse brain exerted a positive or negative influence on the
      results. These results show that our method is indeed applicable to the brain
      tissue.

PMID- 7819522
TI  - Alkalinization during re-oxygenation prevents functional damage by hyperglycaemic
      hypoxia.
AB  - Hyperglycaemia impairs recovery from transient cerebral ischaemia: the importance
      of tissue acidification for this phenomenon has not been clarified in detail. We
      investigated this issue in a less complex in vitro preparation of isolated rat
      dorsal spinal roots exposed for 30 min to hyperglycaemic hypoxia. Peak height of
      compound action potentials recovered minimally in 5 mM bicarbonate. However,
      recovery was greatly improved by addition of the weak base trimethylamine during
      re-oxygenation. Addition of the weak acid propionate had no such effect.
      Cytoplasmic alkalinization improved recovery in a brief time window only:
      application of trimethylamine after 15 min of re-oxygenation was without
      beneficial effect. These data emphasize the importance of cytoplasmic
      acidification for neurophysiological recovery from hyperglycaemic hypoxia during
      the initial period of re-oxygenation.

PMID- 7819524
TI  - Acetylcholine receptor and myogenic factor gene expression in Torpedo embryonic
      development.
AB  - The mRNA levels of acetylcholine receptor (AChR) and myogenic factors were
      followed during embryonic development of Torpedo skeletal muscle and its
      homologue, the electric organ. A different developmental pattern of AChR gene
      expression was found in these two tissues: a slight decrease in the muscle, and a
      marked increase, concomitant with synapse formation, in the electric organ.
      However, the developmental pattern of MyoD and MRF4 mRNA levels was similar in
      both tissues, with no significant changes during development. This is in contrast
      with the sharp increase in the expression of AChR in the electric organ and may
      suggest that the burst in the expression of AChR during the differentiation of
      myotubes into electrocytes is not regulated by changes in the myogenic factor
      mRNA levels.

PMID- 7819523
TI  - beta 2-Syntrophin: localization at the neuromuscular junction in skeletal muscle.
AB  - The syntrophins are a multigene family of proteins which bind C-terminal domains
      of dystrophin, utrophin and homologs thereof. We report here that antibodies
      specific for one isoform, beta 2-syntrophin, labeled only the neuromuscular
      junction (NMJ) in rat skeletal muscle. Anti-alpha 1-syntrophin antibodies gave
      strong labeling of the sarcolemma and NMJ in normal rat and mouse muscle, and
      similar but much weaker labeling in dystrophin-minus mdx muscle. beta 2
      Syntrophin therefore appears to be specific to the NMJ in normal muscle, as is
      utrophin, and may be involved in acetylcholine receptor clustering. alpha 1
      Syntrophin appears to be associated mainly with dystrophin, as expected, but a
      small portion must be associated with another protein, possibly homologs of the
      electric tissue 87K protein.

PMID- 7819525
TI  - Neurotensin transcription is oppositely regulated during development and
      regeneration.
AB  - Our previous work demonstrated that neurotensin mRNA expression was transiently
      up-regulated during development in the hypoglossal motoneurone. The present study
      was carried out to examine how neurotensin mRNA expression changes during nerve
      regeneration. Following either unilateral resection or crushing of the
      hypoglossal nerve, mRNA expression was detected by non-radioactive in situ
      hybridization histochemistry using an alkaline phosphatase-labelled
      oligonucleotide probe. A reduction in neurotensin mRNA was observed on the
      operated side after the nerve injury. It took around 2 months for NT mRNA levels
      to return to normal. Similar down-regulation was observed following crushing, but
      recovery was more rapid than that observed with sectioning, probably due to the
      extent of nerve damage. This finding indicates that neurotensin transcription is
      up-regulated during development but, on the contrary, down-regulated during
      regeneration.

PMID- 7819527
TI  - NK1 receptor expression by cholinergic interneurones in human striatum.
AB  - Neurokinin-1 (NK1) receptor expression in human striatum was analysed using the
      polymerase chain reaction. To determine whether cholinergic interneurones express
      this receptor, in situ hybridization histochemistry was then applied to caudate
      nucleus and putamen. Radioactive oligonucleotide probes specific for choline
      acetyltransferase (ChAT) and NK1 receptor mRNA were used on adjacent cryostat
      sections. All of the 160 identified neurones positive for ChAT were also labelled
      for NK1 receptor. Moreover, in the caudate nucleus, NK1 receptor mRNA was
      detected in a population of large neurones that were not cholinergic. These
      results are consistent with the hypothesis that NK1 receptor-mediated mechanisms
      are involved in the function of cholinergic interneurones. This might be relevant
      to pharmacological or pathophysiological situations where substance P inputs are
      modified.

PMID- 7819526
TI  - Dynamic magnetic resonance imaging of human Rolandic cortex.
AB  - Rolandic cortex was imaged with magnetic resonance (MR) in nine subjects while
      performing a motor activation task. Imaging was performed by a volumetric, T2
      weighted pulse sequence in a conventional 1.5 Tesla scanner during both resting
      conditions and volitional toe flexion and extension of the dominant foot.
      Significant changes in MR signal intensity of 7.8 +/- 2.3% (mean +/- s.e.m.) were
      observed in the medial Rolandic cortex contralateral to the active foot. Changes
      were maximal in the vicinity of the central sulcus, but were also identified
      anteroposteriorly, across successive coronal planes. No significant changes were
      found in the ipsilateral Rolandic cortex or in other brain structures. Volumetric
      functional MRI strategies may provide an important non-invasive tool for
      assessment of cortical motor function.

PMID- 7819528
TI  - Distribution of [3H]alpha,beta-methylene ATP binding sites in rat brain and
      spinal cord.
AB  - The distribution of [3H]alpha,beta-methylene ATP ([3H]alpha,beta-MeATP) binding
      sites in rat brain and spinal cord was examined using autoradiography. It was
      shown that many structures in the CNS are densely labelled, and that the binding
      is displaced by both beta,gamma-methylene ATP and the P2X-purinoceptor
      antagonist, pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS),
      indicating that the binding sites are P2X-purinoceptors. Image analysis revealed
      that the nuclei of the thalamus have the highest density of labelling. Other
      densely labelled structures include: the amygdaloid, substantia nigra, cerebral
      cortex, hypothalamus, caudate putamen, geniculate nuclei, medial habenula and the
      intermediate zone of grey matter in the spinal cord. These results are consistent
      with the limited amount of electrophysiological evidence for the existence of P2X
      purinoceptors in the CNS, and provoke the need for extensive physiological
      studies to establish the roles of P2X-purinoceptors in the CNS.

PMID- 7819529
TI  - Plasticity of mystacial fur representation in SI cortex of adult vibrissectomized
      rats--a 2DG study.
AB  - Localization of cortical representation of the common fur of mystacial pads was
      mapped with 2-deoxyglucose autoradiography in adult rats after vibrissectomy.
      Normal representation of mystacial fur was found in locations outside the
      posteromedial barrel subfield (PMBSF). Vibrissectomy performed in young adult
      resulted in fur inputs activating the PMBSF. This plastic change took more than
      two weeks and less than one month to complete.

PMID- 7819530
TI  - Effect of selective attention on the latency of human frequency-following
      potentials.
AB  - While effects of attention on late and middle latency components of the evoked
      potential have been demonstrated, similar effects on brain stem evoked potentials
      -in particular on the human frequency-following potential (FFP)--are
      controversial. The FFP is a response to tone bursts in the frequency range of
      human language (optimum approximately 350 Hz). It has a latency of approximately
      6.3 ms and is probably generated at a site peripheral to the inferior colliculus.
      We present data showing that the latency of the FFP can be shortened
      significantly (45 microseconds) if the subject is required to attend to the
      evoking auditory tone burst, while the amplitude of the FFP remains unaffected.
      This indicates an attention-controlled influence on signal processing in the
      earliest parts of the auditory pathway.

PMID- 7819531
TI  - Repeated cocaine administration upregulates kappa and mu, but not delta, opioid
      receptors.
AB  - The present study investigated the regulation of opioid receptors following
      chronic repeated cocaine administration. Male Fischer rats were injected with
      saline or cocaine, 45 mg kg-1 day-1, three times daily at 1 h intervals for 14
      days. Using quantitative in vitro autoradiography, the density of kappa receptors
      was significantly higher in the rostral cingulate cortex, rostral caudate
      putamen, caudal olfactory tubercle, and ventral tegmental area following cocaine
      administration. No changes in delta receptor number were detected in any brain
      region examined. Significant mu receptor upregulation was found in the rostral
      cingulate cortex, nucleus accumbens, rostral caudate putamen, and basolateral
      amygdala nucleus of the cocaine-treated animals. These results suggest that
      enhanced dopaminergic activity can regulate mu and kappa opioid receptors.

PMID- 7819532
TI  - Signaling by ATP receptors in astrocytes.
AB  - Treatment of primary cultures of rat cerebral cortical astrocytes with
      extracellular ATP caused a 3- to 4-fold stimulation of mitogen-activated protein
      (MAP) kinase activity. Studies with agonists and antagonists of P1 and P2
      purinergic receptors indicated that this activation is mediated by ATP/P2
      purinergic receptors rather than adenosine/P1 purinergic receptors. Increased
      cAMP levels did not significantly inhibit the activation of MAP kinase by ATP but
      did inhibit the stimulation of MAP kinase by basic fibroblast growth factor, a
      polypeptide growth factor that activates the Ras/Raf kinase signaling pathway.
      These data indicate that ATP/P2 purinergic receptors are coupled to MAP kinase by
      a signal transduction pathway that is independent of the Raf kinase pathway.

PMID- 7819533
TI  - Strong effects of NT/NN peptides on DA D2 receptors in rat neostriatal sections.
AB  - Quantitative receptor autoradiography was performed to test the effects of
      neurotensin (NT)/neuromedin N (NN) peptides on dopamine (DA) D2 receptors in rat
      neostriatal sections. Competition experiments showed that 10 nM of NT, 10 nM of
      NN, and 1 nM of the C-terminal NT-(8-13) fragment produced a 2-fold increase in
      the IC50 value and a 20% decrease in the B0 value of DA for the D2 antagonist
      [125I]iodosulpride binding sites. The results demonstrate a stronger reduction in
      the affinity of DA for neostriatal D2 receptors by the NT/NN peptides in brain
      sections compared with membrane preparations indicating the possible involvement
      of cytoplasmic factors and/or a demand for a more intact membrane structure in
      these receptor-receptor interactions. Further evidence for the hypotheses that
      the C-terminal NT fragments may be among the major ligands for the neostriatal NT
      receptors and that the neostriatal NT receptors may be a new subtype of NT
      receptor has been obtained.

PMID- 7819534
TI  - Herpes simplex virus 1 (HSV-1) helper co-infection affects the distribution of an
      amplicon encoded protein in glia.
AB  - HSV-1 derived amplicons expressing cytoplasmic beta-galactosidase (pA-SF1), or
      plasma membrane targeted TIMP-Thy1 (pA-TT1), were used to transduce glial cells
      in vitro. By monitoring the expression of reporter genes from both amplicons and
      helper virus, we determined that many cells were infected by both particles. In
      glial cells infected only by pA-SF1 beta-galactosidase immunoreactivity was
      restricted to the cytoplasm; co-infection with helper HSV-1 (wild type), resulted
      in additional nuclear beta-galactosidase immunoreactivity. Co-infection of cells
      with amplicon pA-TT1 and helper virus did not affect the plasma membrane
      localization of TIMP/Thy1. Thus, co-infection with wild type helper virus altered
      the localization of an amplicon encoded cytoplasmic, but not plasma membrane
      protein.

PMID- 7819535
TI  - Localization of muscarinic receptor subtypes in brain stem areas regulating
      sleep.
AB  - Muscarinic cholinergic receptors (mAChRs) within the pontine brain stem play a
      key role in generating rapid eye movement (REM) sleep. Using an in vitro
      autoradiographic technique that permits selective labeling of mAChR subtypes by
      radioligand binding, this study provides the first quantitative map of mAChR
      subtypes in cat brain stem areas important for REM sleep generation. M1, M2 and
      M3 mAChR subtypes were distributed heterogeneously throughout the brain stem. For
      all 3 mAChR subtypes, the greatest levels of binding were found in the dorsal
      raphe and locus coeruleus, and the least amount of binding was in the reticular
      formation. These findings are consistent with data from in vivo studies showing
      that multiple mAChR subtypes are involved in REM sleep generation.

PMID- 7819536
TI  - Decreased vasopressin content in parvocellular CRH neurosecretory system of Lewis
      rats.
AB  - Rats possess stress-responsive, vasopressin (VP)-expressing and stress
      nonresponsive, VP-deficient subpopulations of parvocellular corticotropin
      releasing hormone (CRH) neurosecretory cells. Both subpopulations are activated
      by bacterial lipopolysaccharide (LPS) and cytokines. Lewis rats exhibit
      hyporesponsive hypothalamo-pituitary-adrenocortical axes (HPAAs). The Lewis CRH
      neurosecretory system has been reported to be defective in females and normal in
      males. We used post-embedding electron microscopic (EM) immunocytochemistry to
      study baseline levels and LPS-stimulated depletion of neurosecretory vesicles.
      Male Lewis rats possessed normal numbers of CRH+/VP- varicosities and low numbers
      of CRH+/VP+ varicosities, indicating abnormally low release of VP into portal
      blood. This defect contrasts with the reported increase in VP content and release
      in magnocellular neurosecretory cells in Lewis rats.

PMID- 7819537
TI  - KN-62, an inhibitor of Ca2+/calmodulin kinase II, attenuates circadian responses
      to light.
AB  - Expression of immediate early genes and phosphorylation of the transcription
      factor CREB are induced in the suprachiasmatic nucleus after light pulses that
      cause phase shifts of circadian rhythms. To test for a direct role of this
      signalling pathway in mediating circadian responses to light in hamsters, we used
      KN-62 to inhibit the activity of CaM kinase II (known to phosphorylate CREB)
      prior to giving light pulses at times that would normally induce phase shifts.
      Central administration of KN-62 significantly inhibited phase delays and advances
      induced by bright pulses of light. The data support a model for photic responses
      of the circadian clock in the SCN that includes the phosphorylation of CREB by
      activation of CaM kinase II.

PMID- 7819538
TI  - Low dopamine transporter mRNA levels in midbrain regions containing calbindin.
AB  - The dopamine transporter (DAT) is the site at which the neurotoxic metabolite of
      MPTP gains access to midbrain dopaminergic (DA) neurons. However, not all
      midbrain DA neurons degenerate following MPTP treatment. The midbrain DA neurons
      that contain the calcium-binding protein, calbindin-D28k (CALB), are relatively
      invulnerable to MPTP toxicity, compared with DA neurons that lack CALB. Using in
      situ hybridization and immunocytochemical staining techniques in the rat and
      mouse, we now report that there is as much as 10 fold less DAT mRNA in regions
      where DA neurons contain CALB compared with regions where DA neurons lack CALB.
      These data suggest that specific midbrain DA neurons are invulnerable to MPTP
      toxicity not only because they contain CALB, but also because they have
      relatively low DAT activity.

PMID- 7819539
TI  - Regional changes in c-fos mRNA in rat brain after i.v. or i.c.v. NMDA injections.
AB  - These studies were undertaken to determine if convulsant doses of i.c.v. vs i.v.
      administered NMDA exhibit differential specificity for anatomical regions of the
      brain in stimulating c-fos. In rats i.c.v. or i.v. NMDA produced behaviorally
      similar clonic (popcorn) convulsions associated with transient increases in c-fos
      mRNA in different brain areas. Transcription of c-fos mRNA peaked at 30 min post
      treatment regardless of the route of administration. However, the route of
      administration clearly influenced the anatomical specificity of the NMDA-induced
      c-fos mRNA changes. For example, following i.c.v. administration maximal
      stimulation in c-fos mRNA was measured in the cerebellum. In contrast, i.v. NMDA
      produced maximal c-fos mRNA stimulation in the cerebral cortex. Our results
      demonstrate that NMDA has differential anatomical specificity for molecular
      signaling in rat brain and suggest that the route of NMDA administration may
      influence its pathophysiological response.

PMID- 7819540
TI  - C-fos expression in the hypothalamo-pituitary system induced by
      electroacupuncture or noxious stimulation.
AB  - In the anaesthetized rat, low frequency electrical stimulation of the Zusanli
      acupoint (S36) or noxious thermal stimulation caused by immersing the footpad in
      water at 52 degrees C caused marked expression of c-fos in the anterior lobe of
      the pituitary gland, as well as in the arcuate and some nearby hypothalamic
      nuclei. A similar anterior lobe response was caused by immobilization stress in
      awake rats but in this case Fos-immunoreactive cells extended into the
      intermediate lobe and were very abundant in the paraventricular nucleus. It is
      suggested that the anterior pituitary cells that respond to stress are also
      activated by acupuncture or painful stimulation. However, the mechanisms of
      pituitary cell activation seem distinct from those occurring in stress, since
      different hypothalamic nuclei are involved.

PMID- 7819541
TI  - Membrane-associated tubulin in the rat anterior pituitary and GH3 cells.
AB  - Plasma membranes from anterior pituitary lobes of rats and GH3 cells were exposed
      to monoclonal anti-beta tubulin antibodies or normal mouse IgG, and treated with
      FITC-labeled anti-mouse IgG. Specimens were visualized with a microscope equipped
      with epifluorescence optics. Tubulin-specific fluorescence was very prominent in
      membranes incubated with tubulin antibody and was negligible in membranes
      incubated with normal mouse IgG or FITC-labeled anti-mouse IgG alone. Two
      dimensional electrophoresis revealed that 27% of the rat pituitary tubulin is
      beta-tubulin and 73% is alpha-tubulin; 17% of the GH3 cell tubulin is beta
      tubulin and 83% is alpha-tubulin. These results suggest that tubulin is a
      component of plasma membranes of the rat pituitary and GH3 cells.

PMID- 7819542
TI  - c-Fos- and JunB-immunoreactivities in the enteric nervous system of the guinea
      pig ileum.
AB  - We examined the expression of c-Fos and JunB in four immunohistochemical subtypes
      of enteric neurones in the guinea-pig ileum. In whole mount preparations of the
      myenteric and submucous plexuses from isolated segments incubated in normal
      Krebs' solution, increased numbers of many cells expressed visible c-Fos- and
      JunB-immunoreactivities. These increases may have been associated with the
      process of isolation and/or incubation conditions. Depolarizing stimulation by
      veratridine or 50 mM K+ induced further increases of neuronal c-Fos and JunB
      expression with no obvious subtype preference. This probably reflected a non
      specific activation of most enteric neurones by these stimuli and supports the
      idea that expression of c-Fos and JunB in most or all enteric neurones may be a
      useful determinant of activation.

PMID- 7819543
TI  - 'Priming' enhances the relationship of striatal L-dopa concentration to behavior.
AB  - Rats with unilateral 6-hydroxydopamine (6-OHDA) lesions were exposed to L-DOPA
      treatments, 25 mg kg-1 L-DOPA methyl ester/2 mg kg-1 carbidopa, or to saline.
      Fourteen days later, both sets of animals were tested with the L-DOPA/carbidopa
      treatment. The L-DOPA pre-exposed animals exhibited behavioral sensitization as
      indexed by a higher frequency of contralateral rotations. Although striatal L
      DOPA and HVA concentrations were equivalent in the two groups, the L-DOPA
      treatment induced a 10 fold variation in the range of L-DOPA concentrations in
      the 6-OHDA striatum in both sets of animals. Importantly, significant
      correlations between striatal L-DOPA concentration and behavior were obtained
      only for the L-DOPA pre-exposed animals.

PMID- 7819544
TI  - The M1 antagonist pirenzepine suppresses heterosynaptic STD in the CA1 region.
AB  - The effect of the muscarinic M1 and M2 antagonists (pirenzepine and gallamine) on
      heterosynaptic short-term depression (HSTD) of the CA1 population spike was
      studied in rat hippocampal slices. HSTD was evoked by a train of 30-50 pulses at
      5 Hz (theta-like stimulation; TLS) delivered to the stratum oriens. Bath-applied
      pirenzepine (10(-6)-3 x 10(-6) M) significantly suppressed the magnitude of HSTD
      in the tested radiatum input (56 +/- 26% of control, p < 0.05). In contrast,
      gallamine (10(-6)-10(-5) M) did not suppress HSTD (102 +/- 7%). An enhancement of
      HSTD during application of eserine was also antagonized by pirenzepine (71 +/-
      18%, p < 0.01), but not by gallamine (152 +/- 85%). These data suggest that
      acetylcholine synaptically released during TLS of the stratum oriens
      significantly contributes to HSTD in the CA1 region by activation of the M1
      muscarinic receptor subtype.

PMID- 7819545
TI  - Plasticity in spinal opioid control of lower urinary tract function in paraplegic
      cats.
AB  - Spinal cord injury disrupts micturition reflexes, which produces morbidity. The
      contribution of endogenous opioid systems to urinary retention were assessed in
      chronic spinal cats by administering the opioid receptor antagonist, naloxone (5
      500 micrograms kg-1, i.p.), to unanesthetized paraplegic cats while monitoring
      lower urinary tract function and observing hind limb reflexes. While naloxone had
      no overt effect in acute spinal cats, in chronic spinal cats naloxone induced the
      release of large volumes of urine and produced marked hind limb hyper-reflexia.
      Prominent tachyphylaxis and tolerance to the effects of naloxone were evident.
      Immunohistochemical studies indicated a marked increase in leucine enkephalin and
      dynorphin in sacral spinal neurons. Together, these data indicate hyperactivity
      of the endogenous spinal opioid system following recovery from spinal cord injury
      and, furthermore, suggest that the spinal neural circuitry may become 'dependent'
      upon elevated levels of endogenous opioid peptides.

PMID- 7819546
TI  - [The effect of exogenous oxytocin on motor function of mammalian small intestine
      in the lactotrophic period].

PMID- 7819547
TI  - [The sympathetic nervous system does not participate in the development of
      atropine tachycardia].

PMID- 7819548
TI  - [Glycoprotein composition of the supraepithelial mucosa of the digestive tract
      upon administration of pentagastrin and carbacholine].

PMID- 7819549
TI  - [Participation of central opiate receptors in the pathogenesis of adrenal
      arrhythmias].

PMID- 7819550
TI  - [Regularities in the development of aseptic inflammation upon adaptation of the
      body to high-altitude hypoxia].

PMID- 7819551
TI  - [Dynamics of an aseptic inflammatory process in the presence of alpha
      tocopherol].

PMID- 7819552
TI  - [The effect of various lectins on the cholinergic structure of the frog heart].

PMID- 7819553
TI  - [Decrease in the rate of cataract formation in mice with congenital cataract (Cat
      fraser line) under the action of an antioxidant from a screened phenol group].

PMID- 7819554
TI  - [Filterability of EDTA-blood: positive correlation with lymphocyte count].

PMID- 7819555
TI  - [The role of estrogens in regulating expression of prolactin receptors in female
      rat liver cells].

PMID- 7819556
TI  - [Metabolism of sialo-containing compounds in the gastric and intestinal mucosa in
      immobilization stress].

PMID- 7819557
TI  - [Antimutagenic properties of ubiquinone-10].

PMID- 7819558
TI  - [Mechanisms of the vasodilating effect of nitroglycerin and chlorpromazine and
      features of their interaction in a model of a rat isolated thoracic aorta].

PMID- 7819559
TI  - [Ammonium succinate--an effective corrector of cerebral circulatory hypoxia].

PMID- 7819560
TI  - [Pharmacokinetics of antipyrine and isoniazid in rats during dynamics of cold
      adaptation].

PMID- 7819561
TI  - [Regulation of the activity of human natural killer cells by autologous
      interferon].

PMID- 7819562
TI  - [Antioxidant and immunomodulating effect of ceruloplasmin in experimental
      influenza].

PMID- 7819563
TI  - [The role of peritoneal T-lymphocytes and macrophages in triggering stress
      erythropoiesis in vivo after one-time massive blood loss in mice].

PMID- 7819564
TI  - [The phenomenon of death in mice after parenteral introduction of mink blood
      serum].

PMID- 7819565
TI  - [The significance of bacterial agglutination in developing experimental sepsis].

PMID- 7819566
TI  - [Correction of anti-tumor immunity by beta-carotene during experimental
      chemotherapy of malignant neoplasms].

PMID- 7819567
TI  - [Sensitivity of strains of human tumors implanted in immunodeficient mice to
      antineoplastic agents].

PMID- 7819568
TI  - [Ultrastructural analysis of liver biopsies in chronic hepatitis and
      hepatopathies].

PMID- 7819569
TI  - [Morphometric analysis of lung vessels in premature newborn infants].

PMID- 7819570
TI  - [Reactions of arterial and venous skeletal muscle vessels to noradrenaline after
      damage to their endothelium].

PMID- 7819571
TI  - [Asymmetry phenomenon in reactions of frog tongue microvessels].

PMID- 7819572
TI  - [Morphological study of the effect of enzymes on an experimental purulent wound,
      immobilized in textile materials].

PMID- 7819573
TI  - [The effect of experimental hyperprolactinemia on the sexual cycle and
      folliculogenesis].

PMID- 7819574
TI  - [Status of the microcirculatory system, microhemodynamics, and oxygen supply of
      the liver under conditions of disrupted parasympathetic innervation].

PMID- 7819575
TI  - [Morphology of cortical structures in cerebral ischemia and its combination with
      audiogenic seizures].

PMID- 7819576
TI  - [Functional status of the esophagus in cardiospasm from esophagomanometric data].

PMID- 7819577
TI  - Translational research in the San Antonio breast cancer SPORE.

PMID- 7819578
TI  - Translational research in the San Antonio breast cancer SPORE.

PMID- 7819579
TI  - Prognostic factors: rationale and methods of analysis and integration.
AB  - With the proliferation of potential prognostic factors for breast cancer, it is
      becoming increasingly more difficult for physicians and patients to integrate the
      information provided by these factors into a single accurate prediction of
      clinical outcome. Here we review Cox's proportional hazards model, recursive
      partitioning, correspondence analysis, and neural networks for their respective
      capabilities in analyzing censored survival data in the presence of multiple
      prognostic factors, and we present some clinical applications where these models
      have been used.

PMID- 7819580
TI  - Survival analysis of censored data: neural network analysis detection of complex
      interactions between variables.
AB  - Neural networks can be used as pattern recognition systems in complex data sets.
      We are exploring their utility in performing survival analysis to predict time to
      relapse or death. This technique has the potential to find easily some types of
      very complex interactions in data that would not be easily recognized by
      conventional statistical methods. In this paper we demonstrate that there are
      several ways neural networks can be used to find three-way interactions among
      variables. Thus, in data sets where such complex interactions exist, neural
      networks may find utility in detecting such interactions and in helping to
      produce predictive models.

PMID- 7819581
TI  - New magnetic resonance imaging techniques for the detection of breast cancer.
AB  - The importance of contrast agents in enhancing diagnoses from magnetic resonance
      images has been established in numerous cases. However, the development of a
      potent tissue-specific contrast agent, as a sensitive probe for early detection
      and investigation of the physiological characteristics of a tumor, has not yet
      been realized in MR imaging (MRI). In nuclear scintigraphy the technique has been
      demonstrated; however, the poor spacial resolution inherent to the modality and
      the substantial dose of radioactivity administered to the patient has hindered
      its widespread use. This article will review the different classes of contrast
      agents in MRI, with special focus on the strategies involved in the development
      of targeted tissue-specific MRI contrast agents for the early detection of breast
      cancer. The features of a new class of contrast agents for targeted MR imaging
      will be described. Gadolinium-containing melanin polymers (GMP's) have been
      synthesized as MR contrast agents in our laboratory. These GMP's demonstrate
      significantly higher relaxivities than any other paramagnetic contrast agents
      reported; consequently, they are extremely effective contrast enhancing, imaging
      agents by themselves. The successful coupling of these potent GMP's to a
      monoclonal antibody specific for breast carcinoma, the 323/A3 monoclonal
      antibody, suggests that in vivo tissue-specific MR imaging, at the receptor
      level, will become feasible in the near future.

PMID- 7819582
TI  - Immunohistochemical studies of early breast cancer evolution.
AB  - Despite modern therapy, one third to one half of patients who get breast cancer
      will eventually die from it. This disconcerting circumstance has focused
      attention on prevention, and preventing breast cancer will require a much better
      understanding of the biological abnormalities underlying its development and
      progression. Many studies into the mechanisms of invasive breast cancer evolution
      have evaluated presumed precursor lesions (e.g. proliferative disease without
      atypia, atypical ductal hyperplasia, and ductal carcinoma in-situ) for genetic
      alterations known to occur in fully developed invasive carcinomas. This approach
      has shed some light on events which may be important in early malignant
      transformation, including the observations that overexpression of the c-erbB-2
      oncogene and mutations of the p53 tumor suppressor gene are present in
      significant subsets of DCIS, but not PDWA or ADH. Although this approach is
      limited by our incomplete knowledge of cancer genetics, there is still a great
      deal to learn about breast cancer evolution by evaluating cancer-associated genes
      in potential precursor lesions using established techniques such as
      immunohistochemistry and in situ hybridization.

PMID- 7819584
TI  - The p53 tumor suppressor gene in breast cancer.
AB  - Alterations of the p53 tumor suppressor gene are the most common genetic changes
      found so far in breast cancer, suggesting that the gene plays a central role in
      the development of the disease. p53 functions as a negative regulator of cell
      growth, and alterations in the gene lead to loss of this negative growth
      regulation and more rapid cell proliferation. A number of independent groups
      using different methods of detection have shown that p53 alterations are
      associated with more aggressive tumor biologic factors and a poorer prognosis in
      breast cancer patients. Because of its possible role in the regulation of
      apoptosis and response to DNA damage, p53 status could also be a predictive
      marker for response to hormonal or chemotherapy.

PMID- 7819585
TI  - Mechanisms of tamoxifen resistance.
AB  - Though the antiestrogen tamoxifen prolongs disease-free and overall survival in
      the adjuvant setting, and induces remissions in over half of the patients with
      estrogen receptor positive metastatic disease, all patients eventually acquire
      tamoxifen resistance. Furthermore, many of the resistant tumors actually appear
      to be stimulated by tamoxifen just as they are by estrogens. In both animal
      models and clinical specimens, we have found lower tamoxifen uptake and somewhat
      altered tamoxifen metabolism in resistant tumors, but neither appears to explain
      tamoxifen stimulation of the resistant tumors. Nor do estrogen receptor losses or
      mutations appear to explain this phenomenon, although altered expression of
      transcriptional variant forms of the receptor may well contribute. Pure steroidal
      antiestrogens such as ICI 182,780 are capable of reversing tamoxifen-stimulated
      as well as estrogen-stimulated growth of these resistant tumors, and are now in
      clinical trials for this purpose.

PMID- 7819586
TI  - Molecular genetic studies of early breast cancer evolution.
AB  - In the past few years there has been an explosion in the number of patients
      diagnosed with hyperplastic breast disease and in situ breast cancer. Based on
      epidemiological data, these morphologically defined lesions may be categorized as
      those with little malignant potential (e.g. typical hyperplasia or proliferative
      disease without atypia [PDWA], those with significant malignant potential which
      may already be "initiated" (e.g. atypical ductal hyperplasia [ADH]), and early
      "transformed" lesions which are malignant but not yet invasive (e.g. ductal
      carcinoma in situ [DCIS]). They may represent sequential evolutionary stages in
      the ontogeny of invasive breast cancer, with each morphologically defined stage
      resulting from accumulating genetic changes culminating in a transformed clonal
      lineage capable of invasion and metastasis. Using loss-of-heterozygosity (LOH)
      analysis, we are studying the genetic changes associated with these lesions in
      archival tissue samples. 50% (6/12) of the proliferative lesions (PDWA and ADH)
      and 80% of the DCIS shared their LOH patterns with more advanced lesions from the
      same breast, strongly supporting a precursor/product relationship between these
      lesion and the cancers they accompany.

PMID- 7819583
TI  - Tumor suppressor genes and their roles in breast cancer.
AB  - Tumor suppressor genes have been identified by the occurrence of mutations in
      many families with hereditary forms of cancer, exposed during development of the
      tumor by loss of heterozygosity. They have a number of diverse functions. For
      example, both the RB gene of retinoblastoma and the p53 gene, which is commonly
      mutated in breast and colon cancer among others, produce proteins involved in
      distinct steps of cell cycle control, while the nm23 product prevents metastasis.
      Here we review the data developed until now on the possible presence and role of
      mutations in these and other tumor suppressor genes in breast cancer. A more
      complete understanding of the tumor suppressor genes could not only provide
      diagnostic information, but could lead to specific gene therapy to replace
      suppressor functions lost in individual tumors.

PMID- 7819587
TI  - Flow cytometry: potential utility in monitoring drug effects in breast cancer.
AB  - Flow cytometric analysis of DNA ploidy and S-phase fraction are well recognized
      prognostic indicators in breast cancer. The present paper deals with the widening
      of the applications of flow cytometry to monitoring the effectiveness of
      antiestrogen therapy, detecting clonal selection and emergence of drug
      resistance, and monitoring chemosensitizing properties of drugs. Antiestrogen
      activity can be studied by DNA flow cytometry to address clinical research
      problems such as patient-specific pharmacokinetics, dosing compliance, and
      acquired antiestrogen resistance. Patient plasma specimens containing various
      concentrations of triphenylethylenes can be monitored for drug-induced effects
      using cell cycle measurements and correlated to in vivo drug levels. DNA flow
      cytometry has also been instrumental in the study of the effects of prolonged low
      dose (0.5 microM for > 100 days) tamoxifen treatment on human estrogen receptor
      negative MDA-MB-231 cells, where it was shown that tamoxifen may significantly
      alter cell cycle kinetics and tumorigenicity of these cells, selecting a new,
      more aggressive, and rapidly growing clone. Lastly, it has been shown that the
      chemosensitizing properties of another triphenylethylene antiestrogen,
      toremifene, on estrogen receptor negative, multidrug resistant MDA-MB-231-A1
      human breast cancer cells can be studied using flow cytometric analysis.
      Toremifene (and its metabolites N-desmethyltoremifene and toremifene IV) are able
      to "resensitize" MDA-MB-231-A1 cells to vinblastine and doxorubicin, as reflected
      in a marked shift of cells to G2/M phase of the cell cycle. Flow cytometry is a
      widely available technique that might be applied clinically to monitor, at the
      cellular level, drug effects on tumors, including the modulators of drug
      resistance.

PMID- 7819589
TI  - Osteolytic bone metastasis in breast cancer.
AB  - Metastasis of breast cancer cells to bone consists of multiple sequential steps.
      To accomplish the process of metastasis to bone, breast cancer cells are required
      to intrinsically possess or acquire the capacities that are necessary for them to
      proliferate, invade, migrate, survive, and ultimately arrest in bone. These
      capacities are essential for any cancer cells to develop distant metastases in
      organs such as lungs and liver as well as bone. Once breast cancer cells arrest
      in bone, bone is a storehouse of a variety of cytokines and growth factors and
      thus provides an extremely fertile environment for the cells to grow. However,
      breast cancer cells are unable to progress in bone unless they destroy bone with
      the assistance of bone-resorbing osteoclasts. Thus, the capacity of breast cancer
      cells to collaborate with osteoclasts is likely to be specific and is likely
      critical for them to cause osteolytic bone metastases. Evidence to support the
      concept that there is an intimate relationship between breast cancer cells and
      osteoclasts is described using an in vivo bone metastasis model in which human
      breast cancer cells are inoculated into the left ventricle of nude mice. The
      roles of cell adhesion molecules including cadherins and laminin and matrix
      metalloproteinases in the development of osteolytic bone metastases by breast
      cancer are also discussed.

PMID- 7819588
TI  - Heat shock proteins and drug resistance.
AB  - Heat shock proteins (hsp's) are induced in cells when exposed to different
      environmental stressful conditions. We have found that breast cancer cells
      sometimes express high levels of several hsp's, which may both augment the
      aggressiveness of these tumors and make them more resistant to treatment. We have
      shown that hsp70 is an ominous prognostic sign as detected by Western blot assays
      in node-negative breast tumors, and that hsp27 increases specific resistance to
      doxorubicin in breast cancer cell lines. These findings have direct clinical
      application, and suggest that modulating hsp expression may be a therapeutic
      target for reversal of hsp-associated detrimental cellular effects.

PMID- 7819590
TI  - Targeting the EGF receptor in breast cancer treatment.
AB  - Immunotoxins are a relatively new class of cytotoxic agents consisting of a
      catalytic toxin linked to an appropriate targeting ligand. The ligand directs the
      toxin to the surface of a tumor cell, whereupon the toxin enters the cell and
      catalytically inactivates the ribosome, thus disrupting protein synthesis and
      effecting cell death. Monoclonal antibodies (or their fragments) have been most
      commonly used to carry chemically conjugated toxins to proteins or antigens
      overexposed on the tumor cell surface, but specific ligands for tumor cell
      surface receptors could also provide effective targeting. The receptor for
      epidermal growth factor (EGFR) is overexpressed primarily in poor prognosis
      breast cancers that do not respond well to traditional therapies. Because EGFR is
      frequently overexpressed in breast cancer tissue and is associated with a poor
      prognosis, it is an attractive target for antitumor therapy. DAB389EGF is an EGFR
      specific fusion toxin produced with recombinant DNA techniques consisting of
      sequences for the enzymatically active and membrane translocation domains of
      diphtheria toxin plus sequences for human epidermal growth factor. DAB389EGF is a
      potent, EGFR specific, cytotoxic agent which rapidly inhibits protein synthesis
      by a mechanism of action similar to that of diphtheria itself. Preclinical
      studies in the laboratory and in animals now suggest the feasibility of
      investigating such an agent in the targeted therapy of patients with human breast
      cancer.

PMID- 7819591
TI  - Physical exercise and hemostasis.
AB  - A number of hemostatic changes involving platelets, coagulation and fibrinolysis
      have been reported after acute physical exercise. Results have sometimes been
      controversial, due to differences in subjects investigated, type of exercise and
      methods used for hemostatic evaluation. On the whole, physical exercise has been
      shown to induce: (1) increases in platelet number and activity, (2) activation of
      coagulation leading to a slight but significant thrombin generation and (3)
      activation of fibrinolysis. These changes are short lasting. Less known are
      hemostatic changes induced by exercise training programs: a few data are
      available on the effects on platelets and coagulation, whereas studies performed
      on fibrinolysis show a decrease in plasminogen activator inhibitor-1 levels at
      rest and an increase in fibrinolytic capacity after training.

PMID- 7819592
TI  - Monitoring minimal residual disease in acute leukemia: expectations,
      possibilities and initial clinical results.
AB  - Therapy of acute leukemia may be improved by a more accurate assessment of the
      effects of treatment on tumor burden and by anticipating relapse with greater
      precision. The sensitivity limit of assessing residual disease by morphology is
      usually 5%. Several alternative approaches are available to study minimal
      residual disease, defined as the presence of leukemic cells not detectable by
      morphology. These include studies of chromosomal abnormalities by conventional
      karyotyping, flow cytometry, in situ hybridization and polymerase chain reaction
      (PCR), investigation of gene rearrangements by Southern blotting and PCR, and
      immunological methods. Some of these techniques enable the detection of 1
      leukemic cells among 10,000 or more normal cells. In the following, the
      advantages and limitations of sensitive methods for detecting small numbers of
      leukemic cells are reviewed. The rationale for monitoring residual disease in
      acute leukemia and the initial results of studies correlating minimal residual
      disease and clinical outcome are discussed.

PMID- 7819593
TI  - Mast cells and fibroblasts: two interacting cells.
AB  - Mast cell (MC) fibroblast interactions may have a role in health and disease. We
      analyzed the relationships between these cells by utilizing our in vitro model in
      which mucosal (MMC) and connective tissue (CTMC) type MC were cocultured long
      term with different fibroblasts. Mouse 3T3 fibroblasts were used to provide a
      normal microenvironment for MC, while fibroblasts derived from mouse with chronic
      graft-versus-host disease (cGVHD) provided a fibrotic one. We found that both 3T3
      and cGVHD fibroblasts maintain CTMC viability, phenotype and functional activity.
      When MMC were cocultured with 3T3 or cGVHD fibroblasts, they changed their
      phenotype towards that of CTMC. On the other hand, MCs were found to affect
      fibroblast properties. Coculture of MMC on 3T3 monolayers was shown to increase
      Forsmann antigen production and collagen synthesis and stimulate fibroblast
      proliferation. Resting CTMC or CTMC activated by anaphylactic stimuli induced 3T3
      and cGVHD fibroblasts to proliferate more. In addition, CTMC activation increased
      collagen production by 3T3 fibroblasts. In conclusion, fibroblasts were found to
      regulate MC survival and differentiation, whereas MCs were shown to affect the
      biochemical properties of fibroblasts, which can lead to fibrosis.

PMID- 7819594
TI  - Lipoprotein lipase: structure, function and mechanism of action.
AB  - Lipoprotein lipase (LPL) plays a central role in the hydrolysis of circulating
      triglycerides present in chylomicrons, and very low density lipoproteins. The
      active form of the enzyme is a non-covalent homodimer which contains multiple
      functional domains required for normal hydrolytic activity including a catalytic
      domain, as well as sites involved in co-factor, heparin and lipid binding. Recent
      studies involving site-directed mutagenesis, the elucidation of the three
      dimensional crystallographic structure of different lipases, as well as analysis
      of the molecular defects that result in the expression of the familial
      chylomicronemia syndrome have provided new insights into the structure-function
      relationship of LPL. As a result, our understanding of structural domains
      involved in catalysis, heparin, lipid binding, and enzyme-cofactor interaction as
      well as the mechanism of action of LPL as an acylglycerol hydrolase has been
      greatly enhanced.

PMID- 7819595
TI  - Validation of IgA1 and IgA2 measurements by a solid-phase immunoradiometric assay
      in serum and secretions.
AB  - We describe specific, sensitive and reproducible immunoradiometric assays to
      measure total IgA and IgA subclass levels in biological fluids, which take into
      account the problem that polymeric forms are differently recognized in
      immunoassays. Sera from subjects totally deficient in one of the IgA subclasses
      allowed us to ensure the specificity of the subclass assays and to define the
      proportions of IgA1 (84%) and IgA2 (16%) in the normal pooled serum (from 30
      blood donors) used as standard. With purified milk 11-S secretory IgA1 and 11-S
      secretory IgA2, we determined a correction factor for the corresponding polymeric
      forms using, respectively, monomeric IgA1 and monomeric IgA2 from pooled serum as
      standards. With the monoclonal antibodies used, purified 11-S secretory IgA1 was
      similarly recognized by both the total IgA assay and the IgA1 assay; both total
      IgA and IgA1 concentrations were underestimated compared with monomeric IgA or
      monomeric IgA1. In contrast, 11-S secretory IgA2 was better recognized by the
      IgA2 assay than by the total IgA assay and the values were thus overestimates.
      Considering this problem of recognition, we fractionated saliva and lung
      secretions by sucrose density gradient ultracentrifugation before measuring their
      IgA1 and IgA2 levels.

PMID- 7819596
TI  - Treatment of refractory epilepsy with intravenous immunoglobulins. Results of the
      first double-blind/dose finding clinical study.
AB  - Sixty-one refractory epileptic patients (46 with partial epilepsy) were treated
      with intravenous immunoglobulins in a controlled double-blind/dose finding
      clinical trial; 18 (7 females, mean age 18.5 years) received placebo, while 14 (3
      females, mean age 26.2 years, 2 excluded), 14 (4 females, mean age 24.6 years, 1
      excluded) and 15 (5 females, mean age 24.4 years) patients received 100, 250 and
      400 mg/kg per infusion of intravenous immunoglobulins, respectively. Seven
      perfusions were scheduled, four the 1st week, and thereafter one during the 2nd,
      3rd and 6th week. The patients were followed for 6 months. An optional infusion
      was given at the end of the study. A comparison of the mean number of seizures
      per day was made between the baseline (4 weeks before the first infusion) and the
      6th month after the first infusion. Patients were considered responders if they
      had a decrease of at least 50% in daily seizure frequency at the end of the study
      compared with the baseline. We did not find severe adverse events. One patient
      had to stop infusions for possible related side effects (vomiting). When all
      patients were analyzed together, we found a positive trend in favor of
      intravenous immunoglobulin treatment, but this was not significant (P = 0.095).
      There was no relationship between dose and efficacy (P = 0.31). When the largest
      group with partial epilepsy was analyzed separately, we noted 19 responders in
      the test group, compared with 2 in the placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7819597
TI  - Effect of different combinations of antibiotics on experimental septic
      peritonitis in rabbits.
AB  - This study was undertaken to evaluate the efficacy of different combinations of
      antimicrobial agents in the treatment of experimental septic peritonitis. Two
      hundred rabbits, divided into ten groups of 20 rabbits each, were used. Septic
      peritonitis was provoked in two stages: treatment of animals by mechanical lavage
      or antibiotics was performed during the first stage; blood cultures, isolation
      and identification of aerobic and anaerobic bacteria in the peritoneal cavity
      were performed during the second stage. The parameters assessed were survival
      and, in the second phase, the formation of peritoneal abscesses. The most
      significant finding was noted in the first phase, where diffuse peritonitis took
      place, with a very high mortality rate due to bacteremia and sepsis. In both
      blood and pus from the peritoneal cavity cultures in all groups, Escherichia
      coli, Klebsiella pneumoniae and Proteus mirabilis (among the aerobes) and
      Bacteroides fragilis, Clostridium sp. and Peptostreptococcus sp. (among
      anaerobes) were the predominant pathogens identified. High mortality rates
      appeared to be due to the aerobic microbes, particularly Escherichia coli,
      whereas abscess formation was related to the anaerobes, particularly Bacteroides
      fragilis. All antibiotics tested were effective, whether alone or in combination.
      Metronidazole, however, was the most effective in the reduction of intraabdominal
      abscesses. The lowest mortality rate was observed in animals injected with
      piperacillin and a combination of cefoxitin and an aminoglycoside with
      metronidazole. Finally, good peritoneal lavage seemed to be as effective as any
      combination of antibiotic treatment.

PMID- 7819598
TI  - Exogenous CoQ10 preserves plasma ubiquinone levels in patients treated with 3
      hydroxy-3-methylglutaryl coenzyme A reductase inhibitors.
AB  - Ubiquinone is a carrier of the mitochondrial respiratory chain which regulates
      oxidative phosphorylation: it also acts as a membrane stabilizer preventing lipid
      peroxidation. In man the quinone ring originates from tyrosine, while the
      formation of the polyisoprenoid lateral chain starts from acetyl CoA and proceeds
      through mevalonate and isopentenylpyrophosphate; this biosynthetic pathway is the
      same as the cholesterol one. We therefore performed this study to evaluate
      whether statins (hypocholesterolemic drugs that inhibit 3-hydroxy-3
      methylglutaryl coenzyme A reductase) modify blood levels of ubiquinone. Thirty
      unrelated outpatients with primary hypercholesterolemia (IIa phenotype) were
      treated with 20 mg of simvastatin for a 3-month period (group S) or with 20 mg of
      simvastatin plus 100 mg CoQ10 (group US). The following parameters were evaluated
      at time 0, and at 45 and 90 days: total plasma cholesterol, high-density
      lipoprotein-cholesterol, low-density lipoprotein-cholesterol, triglycerides, Apo
      A1, Apo B and CoQ10 in plasma and in platelets. In the S group, there was a
      marked decrease in total cholesterol low-density lipoprotein-cholesterol and in
      plasma CoQ10 levels from 1.08 mg/dl to 0.80 mg/dl. In contrast, in the US group
      we observed a significant increase of plasma CoQ10 (from 1.20 to 1.48 mg/dl)
      while the hypocholesterolemic effect was similar to that observed in the S group.
      Platelet CoQ10 also decreased in the S group (from 104 to 90 ng/mg) and increased
      in the US group (from 95 to 145 ng/mg).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7819600
TI  - What is the correlation between soluble CD23 and IgE levels in human
      immunodeficiency virus-1 infection?

PMID- 7819599
TI  - Cord blood clotting factors in neonates of smoking and non-smoking mothers.
AB  - Since smoking is known to influence hemostasis, the possible impact of maternal
      smoking on hemostatic variables in the newborn was studied. Cord blood clotting
      factors fibrinogen, factor VII, factor VIII:c and factor XIII were measured in
      151 newborns. A significant reduction in birth weight and a rise in the
      placental/birth weight ratio was found in newborns of smoking mothers, which is
      in agreement with the literature. No differences in cord blood clotting factors
      were found between the smoking and non-smoking groups. A possible explanation for
      this, at least for lack of difference in fibrinogen levels, may be that fetal
      lungs were not directly exposed to smoke.

PMID- 7819601
TI  - Peptide sequencing by partial acid hydrolysis and high resolution plasma
      desorption mass spectrometry.
AB  - A method of deriving peptide sequence information using partial acid hydrolysis
      in combination with accurate mass measurements and immonium ion analysis provided
      by high-resolution plasma desorption mass spectrometry has been developed. The
      technique is very simple in terms of the chemistry and involves a short-time (3
      30 min) incubation of the peptide in 1N-6N HCl at 100-110 degrees C with
      subsequent mass spectrometric analysis. Partial acid hydrolysis is found to
      produce sequence-specific segments, often ladder-like, although not always a
      complete set. Two application examples of the method are given: the linear
      peptide bradykinin and desmopressin, a peptide with an internal S-S bond and a
      non-amino-acid constituent. The technique has proved to be particularly useful in
      cases where some a priori information on the peptide structure was already known
      or where the automated Edman degradation technique might yield erratic results or
      not work at all.

PMID- 7819602
TI  - The ultrastructure of the neural plexus in the foot musculature of the desert
      snail Eremina ehrenbergi.
AB  - The foot of the desert snail, Eremina ehrenbergi, is supplied by branches of the
      pedal nerves which enter a coarse-meshed peripheral neural plexus. Light and
      electron microscopic preparations revealed the presence of ganglionic knots
      embedded in the foot musculature. In these knots the neural cell bodies are found
      to be situated on the periphery of neuropile. Cross sections through the
      neuropile demonstrate the presence of many synaptic junctions of the axo-axonic
      type. In some axon profiles light and dense synaptic vesicles are observed. Some
      of the axons which constitute the terminal plexus enter into close apposition
      with muscle cells and definite areas where synaptic transmission in thought to
      occur are well observed. On the basis of these results it can be concluded that
      the neural plexus may be involved in the production of the patterned pedal
      activity in Eremina ehrenbergi.

PMID- 7819603
TI  - Testicular melanin pigments and the gonadal cycle in a tropical wild passerine
      bird, Dicrurus adsimillis (passeriformes, dicruridae).
AB  - Seasonal variation of the coloration of the testes due to the presence of melanin
      pigments was observed in a wild passerine bird Dicrurus adsimillis. The
      proportion of melanin in the testes is highest in the recrudescence period, when
      the lipid content is moderate and cholesterol is present in the tissue in trace
      amounts. In the reproductive period, when lipids are depleted, the melanin
      content is very low; in this stage, cholesterol is stored in the tissue in large
      amounts. During the post-reproductive period, melanin pigment and lipids both
      fall almost to zero level and only traces of cholesterol are to be found. In the
      recrudescence phase, the amount of all three (i.e. melanin pigment, tissue lipids
      and cholesterol) rapidly increases. The probable correlation between
      melanogenesis in testicular tissue and hormones and their lipoid precursors is
      discussed.

PMID- 7819604
TI  - Determination of intracytoplasmic filaments in the chondrocytes of articular
      cartilage.
AB  - Intracytoplasmic filaments were demonstrated in the chondrocytes of articular
      cartilage of cattle at 82 days post partum and at 3 and 4 years of age using
      transmission electron microscopy and immunocytochemistry. Samples of cartilage
      for electron microscopy were processed in a standard way. Immunocytochemical
      procedures were performed with semithin sections made from the material prepared
      for electron microscopy after embedding medium and osmium compounds had been
      eliminated. Vimentin filaments were demonstrated by means of anti-vimentin
      monoclonal antibody visualized by peroxidase-labelled immunoglobulin. Both
      techniques showed that intracytoplasmic filaments were situated around the
      nucleus and only occasionally at the cell periphery, e.g. in cell projections.

PMID- 7819605
TI  - Teratogenic effects of bilirubin--a study using chick embryotoxicity screening
      test (CHEST).
AB  - Using the Chick Embrotoxicity Screening Test (CHEST), two samples of bilirubin of
      different commercial origin were tested on 2, 3 and 4- day old chick embryos.
      Water soluble Bilirubin Lachema (containing 20 mg albumin per 1 ml) had no
      teratogenic effect. On the opposite, Bilirubin Merck (containing 8 mg albumin per
      1 ml) manifested an apparent teratogenic potential when single doses 0.2 and 0.6
      micrograms were administered intraamniotically on day 4. Dose-dependent
      malformations of brain and eyes, cleft beak and reduction deformities of limbs
      were observed. No such effects could be produced by administration of Bilirubin
      Merck on either day 2 and 3. A tentative explanation of the difference between
      teratogenic properties of Merck and Lachema bilirubin preparations may be sougth
      in the different proportion of the free and albumin bound fractions.

PMID- 7819606
TI  - 'Double-head' antlers in red deer Cervus elaphus ssp. in which the antler cores
      survived the death of the cortex.
AB  - An unusual case of spike antlers in male red deer is described in which the
      antler core apparently survived the partial mineralization of the cortex in the
      first rut and then in the next year supported a new, "antleroma-like" growth. On
      one side of the antler beam a "separation gap" developed between the living core
      and the dead cortex. On the opposite side a new growth of antler tissue was
      observed; this was made of spongious bone which in some areas partially resembled
      peruke-like growth and in others resembled antler "pearls". This new tissue,
      which developed probably in the second antler cycle, grew in the right antler
      from the base to the apex but in the left antler it was limited to the lower
      portion of the beam. This new tissue might still have been covered with velvet
      when the deer was shot. It is speculated that hypoandrogenism or partial lack of
      testosterone receptors was responsible for the survival of the antler core and
      the subsequent proliferation of new antler tissue in the following year.

PMID- 7819607
TI  - Development of spatial relations of shoulder and brachium in embryonal chick
      wing.
AB  - The linear marking method was employed to study morphogenetic movements of
      tissues involved in the development of the definitive position and shaping of the
      shoulder and arm. Chick embryos in the range of embryonal day 3.5 to 4.5 were
      used with the following results: -Asymmetrical growth of the early wing bud and
      the oblique position of humerus anlage in the early wing bud as proposed by
      Saunders (1948) and Seichert (1965) were confirmed. -It was found that the
      cranial ascend of the shoulder (Seichert and Knospe 1992) is accompanied by the
      slight ventromedial rotation of the complex consisting of the scapula and
      coracoid. -Torsion along the longitudinal axis of the stylopodium was observed:
      the proximal part of the stylopodium (both the humerus anlage and related soft
      tissues) moves in the sense of supination, the distal part moves in the sense of
      pronation.

PMID- 7819608
TI  - Effect of cadmium chloride on the pituitary, thyroid and gonads in the catfish,
      Clarias batrachus (Linn.).
AB  - The effect of cadmium chloride on the pituitary ACTH cells, gonadotropin- and
      thyrotropin-secreting cells, thyroid gland and gonads of the catfish, Clarias
      batrachus was investigated. Exposure to cadmium chloride caused a significant
      increase in the ACTH cell nuclear indices at day 7, 14 and 28, whereas the
      thyrotropin- and gonadotropin-secreting cells showed inactivation and
      accumulation of secretary products. The epithelial height of the thyroid
      follicles was also significantly reduced (P < 0.001) as compared to that of the
      untreated control fish. In experimental female fish, the gonosomatic index had
      undergone a significant reduction at all intervals studied (day 7, 14 and 28).
      However, in the male catfish a significant reduction in the gonosomatic index was
      observed only after exposure for 28 days. Ovarian maturation seems to have become
      arrested at perinucleolar stage and spermatogenesis at spermatocyte stage. The
      possible involvement of the hypothalamo-hypophyseal system in gonadal regression
      was discussed.

PMID- 7819609
TI  - Hormonal and histological effects of chronic caffeine administration on the
      pituitary-gonadal and pituitary-adrenocortical axes in male rabbits.
AB  - Daily administration of caffeine (30 or 60 mg/kg) to mature male rabbits for four
      consecutive weeks caused an increase in the plasma follicle stimulating hormone
      (FSH) and a decrease in the luteinizing hormone (LH). Testosterone was increased
      with the higher dose only while adrenocorticotrophic hormone (ACTH) was not
      altered by either one. These results suggest that the effects of caffeine on the
      two gonadotrophic hormones, FSH and LH, involve two separate pathways. The light
      microscope study revealed reduced sizes of the seminiferous tubules, inhibited
      spermatogenesis, fatty degeneration of the liver and hepatic lesions. The adrenal
      glands exhibited signs of stimulated steroidogenesis. It is concluded that long
      term intake of caffeine induces suppression of spermatogenesis mainly through
      inhibition of FSH release and this effect is maintained even in the presence of
      normal or high levels of testosterone and LH.

PMID- 7819610
TI  - The neural organization of the paired pedal ganglia of the desert snail Eremina
      ehrenbergi.
AB  - A surface map of the paired pedal ganglia of Eremina ehrenbergi has been
      constructed. The pedal ganglia contain large (phi < 80 microns), middle (phi 40
      60 microns) and small (phi 15-30 microns) sized neurones. Most of the somata are
      ipsilateral to their nerves, but there are few cases in which contralateral
      neurones were observed. The neurones in a ganglion send their axons primarily to
      the nerves originating from the ganglion, but they have also connections with
      neurones in other central ganglia.

PMID- 7819611
TI  - Human pancreatic islet isolation and transplantation.

PMID- 7819612
TI  - Differences in the procurement of organs and tissues by health care
      professionals.
AB  - BACKGROUND: The act of donating organs is familiar to most health care
      professionals (HCPs). However, the process of tissue and cornea donation is not
      nearly as well known. Most studies of the donation process have neglected the
      issue of tissue and cornea donation. This study offers some preliminary data
      concerning the differences between organ and tissue and cornea donation
      processes. As well, this is one of the first studies to report an eligibility
      rate for tissues among hospital deaths. METHODS: During a 5-month period in 1989,
      the charts of all patients (n = 233) who died in the study hospital were reviewed
      on a weekly basis to establish eligibility to donate organs, tissues and corneas.
      A case series of 50 eligible patients cases was selected for in-depth interviews.
      Cases were defined as those patients who were eligible to donate tissues or
      organs. The patient's attending physician, house officer, and primary nurse were
      interviewed using an open-ended interview format. These audiotaped interviews
      focused on the events surrounding the patient's death, focusing on the issue of
      donation. We also collected information concerning HCP knowledge of the medical
      criteria for donation and their attitudes toward donation. Consent was obtained
      from all HCPs before beginning the interview process. RESULTS: Of the 233 deaths,
      4.3% were eligible to donate organs, 11.2% were eligible to donate tissues, and
      18.9% were eligible to donate corneas. On the basis of our interview data we
      found that all eligible organ donors were identified and their families asked by
      at least one member of the patient's health care team to consider donation. HCPs
      were less successful identifying tissue patients: 30 of the 41 tissue donors
      (73.2%) were identified and only 65.9% of donor families were asked to donate.
      Rates of consent to donation were lower than might be expected based on public
      opinion polls. 33.3% of families consented to organ donation while only 29.6%
      consented to donate tissue and cornea. CONCLUSION: HCPs performed less
      efficiently in terms of the procurement process for tissues and corneas as
      compared to organs. They were also less knowledgeable about the donation criteria
      for tissues and corneas than organs. They generally exhibited more positive
      attitudes about corneal donation. More education of HCPs is necessary before we
      can optimally procure tissues for transplantation.

PMID- 7819613
TI  - Rapid detection of cytomegalovirus antigen on alveolar cells in bronchoalveolar
      fluid from transplant patients with cytomegalovirus pneumonia.
AB  - Cytomegalovirus-specific mouse monoclonal antibodies and immunomagnetic beads
      conjugated with sheep anti-mouse immunoglobulin G were used to screen for
      cytomegalovirus (CMV) antigen expressed on the surface of alveolar cells in
      bronchoalveolar lavage (BAL) fluid from 23 transplant recipients with
      interstitial pneumonia. The beads formed rosettes around the cells when CMV
      antigen was present on the cell surface. Results could be evaluated by light
      microscopy within 2 hours of receiving the specimen. Cells in BAL fluid obtained
      from 15 immunocompetent individuals served as controls. Cytomegalovirus antigen
      was expressed on the surface of the alveolar cells from 12 transplant recipients
      and detected by this method as rosette formation on 1-8% of the cells. CMV was
      isolated from culture of cells in BAL fluid and blood from all these patients
      except 1, while intracellular CMV antigen was detected by monoclonal antibodies
      and immunofluorescence in 3 only. Serological changes, indicating an active CMV
      infection, were present in 11/12 patients. One patient with a CMV pneumonia,
      later confirmed by autopsy, failed to respond with any antibody titer. No rosette
      formation occurred on alveolar cells from any of the 15 immunocompetent controls.
      Thus, the method studied appears to be a valuable complement to other diagnostic
      methods for CMV pneumonia in transplant recipients. When correlated with the
      isolation of CMV from culture, the sensitivity was 100% and specificity 92%.

PMID- 7819614
TI  - Pre-emptive renal transplantation in children: report of the North American
      Pediatric Renal Transplant Cooperative Study (NAPRTCS).
AB  - Of 2213 primary transplants reported to NAPRTCS between 1/1/87 and 10/31/92, 581
      (26.3%) were performed without prior dialysis. The rate of pre-emptive
      transplantation (PET) differed by donor source, 35.7% LD and 16.1% CD (p <
      0.001); gender, 29.6% male and 21.1% female (p < 0.001); race, 30.1% white, 16.1%
      black, 19.5% hispanic, and 20.2% other (p < 0.001); recipient age, 0-1 yr 18.7%,
      2-5 yr 27.9%, 6-12 yr 30.5%, and 13-17 yr 22.8% (p < 0.001). The graft survival
      rate was significantly better for both the LD (p < 0.01) and CD (p = 0.01) grafts
      in the pre-emptive group; however, the differences were not significant after
      adjustment for other variables. The major reasons for pre-emptive transplantation
      were the parents' desire to avoid dialysis and the recommendation of the
      nephrologist/surgeon. The data indicate that pre-emptive transplantation does not
      adversely impact on transplant outcome and that the desire to avoid dialysis is
      the primary motivating factor.

PMID- 7819615
TI  - Soluble interleukin-2 receptor monitoring during bacterial and viral infections
      in liver transplant recipients: a comparative evaluation.
AB  - We evaluated the significance of serial sIL-2R serum levels as a differential
      marker of immune activation during bacterial versus viral infections in liver
      transplant recipients. A comparative evaluation of sIL-2R levels was performed in
      76 liver transplant recipients (51 pediatric and 27 adult) during bacterial
      versus viral infections at 7 days prior to infection diagnosis (DAY-7), the day
      of diagnosis (DAY 0), peak sIL-2R level and at the end of therapy (END). There
      were no significant elevations at any time point during bacterial infections in
      either adult or pediatric transplant recipients. However, adult recipients
      demonstrated significant elevations during viral infections when comparing DAY-7
      to PEAK (3840 +/- 830 vs 7225 +/- 2814 p = 0.03), with PEAK levels significantly
      higher during viral versus bacterial infections in this population (7225 +/- 2814
      vs 4195 +/- 1819). Pediatric recipients demonstrated similar increases in sIL-2R
      serum levels during viral infections from DAY-7 to PEAK (4932 +/- 887 vs 11323 +/
      2794 p = 0.0012). Significant decreases from PEAK to END were noted during viral
      infections in both adult and pediatric recipients (7225 +/- 2814 vs 2911 +/- 1376
      p = 0.01 and 11323 +/- 2794 vs 5214 +/- 2403 p = 0.006). Pediatric recipients had
      higher mean sIL-2R levels than adult recipients at all time points during viral
      infections. In conclusion, significant elevations in mean sIL-2R serum levels
      were observed during viral but not bacterial infections in pediatric and adult
      liver transplant recipients. This suggests that serial sIL-2R monitoring is a
      valuable immunologic marker of viral pathogenesis and may be useful in monitoring
      the progression of viral infections as well as response to antiviral therapy.

PMID- 7819616
TI  - Incidence of vascular complications in kidney transplantation: is there any
      interference with the nature of the perfusion solution?
AB  - Two non-randomized groups of 100 kidney transplants each were compared in
      relation to the flush-out solution used. The two groups were similar with the
      exceptions of the number of multiple artery kidneys and the proportion of kidneys
      procured in our center. The rate of vascular complications such as arterial
      venous thrombosis and renal artery stenosis was higher in the Eurocollins (19)
      group than in the UW group (4) p < 0.01, even if the multiple artery kidneys are
      excluded. These results need to be confirmed by a randomized study but it is
      clear that the use of the UW solution leads to a better arterial flow with fewer
      vascular complications.

PMID- 7819617
TI  - Mouse antibody-coated lymphocytes during OKT3 therapy in liver transplantation.
AB  - Flow cytometry has been a technique in search of a use in transplantation. With
      each new monoclonal antibody, it has been hoped that the secrets of rejection
      would be unlocked. The usefulness of CD3+ T-lymphocyte counts to predict
      successful treatment of organ transplant rejection has been called into question.
      CD2+, CD3+, and mouse antibody-coated CD3 lymphocytes were followed by flow
      cytometry in 44 liver transplant patients during OKT3 therapy for induction or
      rejection. CD3+ lymphocyte counts did not predict successful management of
      rejection by OKT3. When expressed as percentages of the total lymphocyte count,
      an increasing trend in CD2+ and mouse antibody-coated CD3+ lymphocytes after day
      7 of OKT3 therapy portended persistent or recurrent rejection within 2 months of
      treatment. It is uncertain if the increasing population of mouse antibody-coated
      CD3 cells is due to an immune phenomen or decreased clearance by an ailing liver.
      Care should be taken when using CD3 lymphocyte counts as indicators of adequate
      OKT3 therapy in liver transplantation.

PMID- 7819619
TI  - Coronary artery surgery.

PMID- 7819618
TI  - Preservation injury in clinical liver transplantation: incidence and effect on
      rejection and survival.
AB  - The distribution of the severity of preservation injury (PI), its association
      with acute early rejection, and its effect on graft and patient survival were
      examined in 151 patients transplanted between 9/88 and 12/91. PI was graded into
      mild, moderate and severe using prothrombin time (PT) on the 2nd POD and peak AST
      and ALT levels of the first 3 days after transplant. Of the 151 patients, 104
      (68.8%) had minimal, 24 (15.9%) had moderate, and 23 (15.3%) had severe PI. The
      rate of early rejection, within 21 days after transplant, (54.8% vs 54.2% vs
      52.2%) and its timing (10.0 +/- 0.5 vs 8.8 +/- 0.8 vs 8.9 +/- 1.4 days) as well
      as the incidence of steroid-resistant rejection (21.4% vs 33% vs 30%) did not
      differ significantly among groups. Graft survival was significantly lower in the
      severe PI group than among patients with minimal PI at 3 months and 24 months
      (65.2% vs 86.2%; p < 0.05 and 58.3% vs 82.7%; p < 0.05, respectively). Patient
      survival at 3 and 24 months was similar among the groups (91.1% vs. 95.8% vs
      86.9% and 81.9% vs 91.1% vs. 74.3%). We conclude that the cellular damage
      associated with preservation injury does not predispose to development of acute
      rejection.

PMID- 7819620
TI  - Imaging and echocardiography.

PMID- 7819621
TI  - Coronary bypass grafting economics, including rehabilitation.

PMID- 7819622
TI  - The biology of saphenous vein graft occlusion: etiology and strategies for
      prevention.
AB  - Saphenous vein graft failure remains a significant clinical and economic burden.
      Although increased use of arterial conduits has improved long-term outcome, the
      majority of bypass procedures continue to use saphenous vein. Early vein graft
      patency is maximized by avoiding damage at the time of implantation, meticulous
      surgical technique, and appropriate use of antithrombotic therapy. No surgical
      technique or pharmacological intervention, however, has been shown to prevent
      late occlusion, which results from the progression of intimal vascular smooth
      muscle cell proliferation and superimposed atheromatous changes. Over the last
      few years, there has been a dramatic increase in our understanding of the biology
      of the vessel wall and the cellular and humoral influences on the process of
      intimal vascular smooth muscle cell proliferation. This has been possible
      principally through the advancement and application of molecular biological
      techniques. Although pharmacological therapies to prevent intimal hyperplasia
      continue to be evaluated, it is again the new series of strategies made possible
      by molecular biology that provide the most exciting prospects for treatment.
      Development of specific antibodies, antisense oligonucleotides, and vascular gene
      transfer represent potentially effective therapies, not only for the prevention
      of vein graft failure but also for a whole range of cardiovascular diseases.

PMID- 7819623
TI  - Coronary bypass surgery in women.
AB  - Cardiac surgeons have long appreciated that coronary artery bypass grafting may
      differ in its success for men and women. Early studies reported that coronary
      artery bypass grafting was associated with a higher early mortality in women,
      although long-term survival was similar in both sexes. A consistent finding was
      that women were more symptomatic, with a greater number of adverse risk factors
      at time of surgery, although they had less coronary disease and better cardiac
      function. Recent studies suggest that their disadvantageous clinical profile
      remains, but that they are now burdened with increased coronary disease and
      poorer cardiac function. There is increasing evidence that women are
      underreferred for coronary angiography, although it would appear that once
      investigated, they receive appropriate referral for coronary artery bypass
      grafting. These findings are not universal, and there are significant differences
      in clinical practice between institutions.

PMID- 7819624
TI  - Coronary artery bypass grafting for left ventricular dysfunction.
AB  - In patients with severe coronary disease and poor left ventricular function,
      coronary artery bypass grafting has a positive impact on long-term survival. In
      presence of angina or documented ischemia, it is beneficial in protecting
      functioning muscle against future infarction. In patients with heart failure and
      no angina, it is a rational option when large areas of akinetic but viable
      myocardium are identified preoperatively; under these circumstances, recovery of
      myocardial function is the goal of coronary revascularization. Obviously,
      reliable methods of assessing myocardial viability and contractile reserve are
      required for an accurate selection of patients. Advances in perioperative
      management, including myocardial preservation, have consistently reduced the
      operative risk in the most recent series, and more appropriate selection criteria
      have substantially contributed to the improved long-term survival. Variables
      associated with higher hospital mortality as well as factors influencing long
      term outcome have been identified. The beneficial effect of coronary artery
      bypass grafting on the functional status of patients has been documented in
      several studies, and the improvement in left ventricular function has been
      objectively demonstrated. The concepts and the data presented in this review may
      help to define the present role of coronary artery bypass grafting in the
      treatment of ischemic cardiomyopathy.

PMID- 7819625
TI  - Factors influencing mortality and myocardial infarction after coronary artery
      bypass grafting.
AB  - Although the mortality for coronary artery bypass graft surgery has declined,
      some categories of patients are still recognized as being at greater risk.
      Because the mortality, even for most patients with risk factors, is less than
      10%, evaluating this risk and any improvement arising from changing techniques
      requires thousands of cases. The need for these large patient numbers makes the
      evaluation of changes difficult. Even when other risk factors are accounted for
      in the mortality estimate, the patient's age remains an important factor,
      although there is no obvious reason why this should be so. Similarly, female sex
      is well recognized as a risk factor. However, the tendency for women to have a
      smaller body surface area and corresponding smaller arterial diameters may be the
      explanation. Perfusion time appears to have a strong influence on mortality after
      it exceeds about 90 minutes, and a similar influence on myocardial infarction
      also appears to be present. The increased risk of myocardial infarction with
      unstable angina may relate to disruption of the normal endothelial vasodilatation
      caused by nitric oxide.

PMID- 7819626
TI  - Cerebral complications after coronary bypass grafting.
AB  - As the mortality associated with coronary artery bypass grafting has fallen,
      morbidity has become an increasing concern both by the medical profession and the
      general public. Postoperative quality of life, including the socioeconomic
      concern of returning to gainful employment, is of supreme importance. It is in
      this regard that brain injury following coronary artery bypass grafting is
      devastating if it leaves the patient with persistent motor, sensory, behavioral,
      or intellectual deficiencies. This paper reviews the cerebral complications
      following surgery for coronary artery disease. The extent of the problem is
      defined, and pathological mechanisms of injury together with methods employed to
      investigate cerebral pathology and physiology are reviewed. Finally,
      interventions which have been and are currently employed in an attempt to reduce
      cerebral injury are discussed.

PMID- 7819627
TI  - Reoperative coronary artery bypass grafting.
AB  - In recent years reoperative coronary artery bypass surgery has become
      increasingly more commonplace. This article reviews the current status of this
      procedure with regard to patient population, risk factors, and long-term follow
      up. Important aspects of the specific technical considerations involved in
      reoperative surgery are also reviewed and evaluated.

PMID- 7819628
TI  - Long-term vein graft patency.
AB  - In spite of their limited long-term patency, saphenous vein grafts continue to be
      widely used in patients undergoing coronary artery bypass surgery. Careful
      surgical technique reduces to some extent the vascular endothelial damage
      occurring during surgery. Antiplatelet and antithrombotic therapy decrease vein
      graft occlusion in the short term but probably not in the long term. Lipid
      lowering therapy improves late vein graft patency, but its long-term benefit must
      be more firmly established. The value of external stenting for reducing intimal
      thickening of vein grafts remains controversial. The role of the internal
      thoracic artery as a bypass conduit is well established, but the mid- and long
      term usefulness of other arterial conduits requires further study. Artificial
      grafts and allografts are still in the early stage of development. The
      indications, technical limitations, and long-term results of reoperation and
      balloon angioplasty have recently become better defined. However, more data are
      needed on the safety and efficacy of new technological devices such as
      intravascular stents, atherectomy, and laser angioplasty. Finally, randomized
      trials comparing different revascularization strategies in the management of high
      risk patients with old, degenerated saphenous vein grafts are needed for the
      future.

PMID- 7819629
TI  - Long-term survival after coronary artery bypass grafting.
AB  - The most quoted long-term outcome studies from the coronary artery bypass surgery
      literature were performed in the 1970s, and these trials--the Coronary Artery
      Surgery Study, the Veterans Administration Study, and the European Cooperative
      Study--added significantly to our knowledge of the efficacy of bypass surgery.
      However, important studies are still being performed and are refining our
      knowledge of long-term outcomes. This review covers early factors that affect
      long-term outcome, and recent information concerning particular subgroups of
      patients undergoing bypass surgery. In addition, new information is becoming
      available about the relative roles of percutaneous transluminal coronary
      angioplasty and coronary artery bypass grafting, and these studies are also
      discussed.

PMID- 7819630
TI  - Coronary stenosis significance: lessons learned from recent trials.

PMID- 7819631
TI  - What's new in transesophageal echocardiography?
AB  - Transesophageal echocardiography continues to evolve as an important
      complimentary technique to transthoracic echocardiography for the diagnosis and
      management of various cardiovascular disorders. Improved transducer technology
      has expanded the indications to include assessment of ventricular function,
      especially in the intraoperative setting. Automatic border detection may further
      simplify the quantitative approach of transesophageal echocardiographic-guided
      assessment of ventricular function. Another area in which the technique continues
      to develop is valvular disease, especially for planimetry of the aortic valve
      area in aortic stenosis. The technique continues to be used in the evaluation of
      endocarditis, especially prosthetic valve involvement, and for the evaluation of
      the patient with a potential cardiac source of emboli. Clearly, transesophageal
      echocardiography plays an important role in evaluating lesions of the aorta,
      particularly dissection, where it may be the diagnostic test of choice.
      Undoubtedly, the technique will continue to evolve with changes driven by
      developments in technology.

PMID- 7819632
TI  - Evolving usage of pediatric cardiac catheterization.
AB  - The use of catheterization for the diagnosis of congenital heart disease has
      decreased dramatically in the last decade. The development of two-dimensional
      Doppler echocardiography has changed the practice of pediatric cardiology,
      combining exquisite imaging with Doppler-derived hemodynamic information.
      Angiographic cardiac imaging is required for those areas inaccessible to
      ultrasonography, such as the distal great arteries and abnormal venous
      connections, and also in complex postoperative conditions. To further decrease
      the need for angiography, transesophageal echocardiography, magnetic resonance
      imaging, radionuclide angiography, and spiral computed tomography have been
      employed as noninvasive substitutes in those areas. Of these modalities, magnetic
      resonance imaging appears to be the most promising. Currently, angiography is
      used almost exclusively for interventional purposes. The increased imaging
      versatility afforded by these new modalities has important financial
      consequences, and requires a responsible economic approach. This article compares
      the role and requirements of invasive cardiac imaging in the catheterization
      laboratory with those of these newly developed techniques.

PMID- 7819633
TI  - Noninvasive imaging of the cardiovascular system with electron beam computed
      tomography and magnetic resonance imaging.
AB  - Two new noninvasive imaging modalities have emerged in recent years that provide
      images of the heart and great vessels with high temporal and spatial resolution:
      electron beam (or ultrafast) computed tomography and magnetic resonance imaging.
      Because both modalities acquire images in three dimensions, they can provide
      unique diagnostic information above and beyond that of more traditional
      noninvasive modalities such as two-dimensional echocardiography and radionuclide
      techniques. This review discusses the technical evolution and clinical
      application of these two imaging techniques, with particular emphasis on progress
      made over the past year. Specific areas addressed for each include technical
      aspects and clinical applications from both the imaging and physiology
      perspective.

PMID- 7819634
TI  - Recent technical advances in digital coronary angiography.
AB  - Digital coronary angiography systems are widely available in interventional
      catheterization laboratories. Although quantitative coronary angiography is an
      important and widely used endpoint for research and clinical trials, the
      capabilities of digital imaging now available are underused in clinical practice,
      and potential capabilities have not yet been developed or practically
      implemented. This paper reviews recently published technical developments in
      digital angiography and fluoroscopy, including radiographic dose reduction
      methods that have minimal impact on image quality, image processing and display
      methods for improving image quality, new algorithms and validations for
      quantitative coronary angiography, and methods for obtaining images of and
      analyzing the complete three-dimensional coronary tree. These advancements may
      lead to reduced radiation exposure, improved image quality, better automated
      stenosis quantitation programs, and extraction of new and useful kinds of
      information from the coronary angiogram.

PMID- 7819635
TI  - Comparison of smoking habits between patients with surgically confirmed herniated
      lumbar and cervical disc disease and controls.
AB  - There have been numerous studies that implicate cigarette smoking as a risk
      factor for the development of back pain or disc disease. The purpose of this
      article is to review patients who underwent surgery for cervical or lumbar
      radiculopathy and to investigate the relationship between cigarette smoking and
      development of surgical disc disease. A cigarette smoking study of 205 surgical
      patients with lumbar and cervical disc diseases was done, with the surgical
      patients compared to 205 age-sex-matched inpatient controls during 1987-1988.
      This study was conducted at the Pennsylvania Hospital in Philadelphia,
      Pennsylvania. There were 163 patients with lumbar disc disease and 42 patients
      with cervical disc disease. The ratio of men to women was 1.5:1 for lumbar disc
      and 2.5:1 for cervical disc disease. Smoking history (current and ex-smokers) was
      strikingly increased in both prolapsed lumbar intervertebral disc (56% vs. 37% of
      controls, p = 0.00029) and cervical disc disease (64.3% vs. 37% of controls, p =
      0.0025). Calculated relative risks for smokers were 2.2 for lumbar disc and 2.9
      for cervical disc diseases. This association between cigarette smoking and disc
      disease was more significant when comparing between current smokers versus
      nonsmokers (p = 0.000011 for lumbar disc disease, and p = 0.00064 for cervical
      disc disease). Relative risks for current smokers were 3.0 for lumbar disc and
      3.9 for cervical disc diseases. This correlation was significant for both males
      (p = 0.000068 for lumbar disc disease, p = 0.043 for cervical disc disease) and
      females (p = 0.018 for lumbar disc disease, p = 0.006 for cervical disc
      disease).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7819636
TI  - Non-specific low-back pain among schoolchildren: a field survey with analysis of
      some associated factors.
AB  - A study population composed of 1,755 children 8-16 years of age were surveyed
      using a 15-item, self-administered questionnaire. The response rate was 97.7%.
      The purpose of the survey was to evaluate the possible association between low
      back pain and certain social factors and predicaments. Descriptive statistics and
      logistic regression analysis showed that parental history of treated low-back
      pain (adjusted odds ratio 2.10; p < 0.001), competitive sports activity (adjusted
      odds ratio 1.73; p = 0.003), and time spent watching television (adjusted odds
      ratio 1.23; p = 0.05) significantly increased the risk for low-back pain among
      children, controlling for the child's age and gender.

PMID- 7819637
TI  - Clinical and roentgenographic results of decompression for lumbar spinal
      stenosis.
AB  - We reviewed 118 patients who underwent lumbar decompression without fusion for
      acquired lumbar spinal stenosis between 1980 and 1991. Fifty of these patients
      (15 men, 35 women) were clinically and roentgenographically reexamined, with
      quantification of postoperative degenerative changes. The presence of
      preoperative spondylolisthesis and a postoperative change in spondylolisthesis
      portended poor outcome. Men had better mean surgical outcome scores than did
      women, and 6% of the men and 28% of the women underwent further surgery for
      recurrent stenosis or instability. Women had larger mean postoperative changes in
      spondylolisthesis than did men. Patients with mild preoperative spondylolisthesis
      developed a larger slip after the procedure than did those with no preoperative
      slip. Women and patients with preoperative spondylolisthesis may require changes
      in existing treatment modalities to improve outcome or alterations in long-term
      expectations after lumbar decompression for stenosis.

PMID- 7819638
TI  - Cross-sectional area of the stenotic lumbar dural tube measured from the
      transverse views of magnetic resonance imaging.
AB  - The cross-sectional area of the lumbar dural tube was calculated from transverse
      slice lumbosacral magnetic resonance images (MRI) using the simple geometric
      formulas and computerized digitizer in 51 patients with low-back pain only, 79
      with mainly radicular symptoms, and 53 with intermittent claudication, and in 39
      controls with confirmed symptomatic lesions at a nonlumbar level or of a
      nonspinal organ. Findings suggesting developmental narrowing of the spinal canal
      were found not only in the intermittent claudication group, but also in the
      radicular pain group. Cross-sectional area of < 100 mm2 at more than two of three
      (L2/3, L3/4, and L4/5) intervertebral levels was highly associated with the
      presence of intermittent claudication. The cross-sectional area value obtained
      with the simplified geometric formulas was highly correlated with that calculated
      with the digitizer, indicating that this simple method can be used with MRI in
      outpatient clinics for the rapid determination of the most stenotic portion of
      the dural tube.

PMID- 7819639
TI  - Biomechanical analysis of screw load sharing in pedicle fixation of the lumbar
      spine.
AB  - Segmental fixation of the spine by means of rods or plates and pedicle screws
      posteriorly usually results in a stable and rigid construct. The magnitude of the
      stresses on the instrumentation particularly at the bone-screw and rod (or plate)
      interfaces will depend on the load distribution between the bone and the implant
      as well as the number of sites of bone purchase of the implant. If a fusion is to
      be obtained in the case of a degenerative spine, the role of the instrumentation
      is to prevent translation of the motion segments, thereby allowing the
      compressive loads to be transmitted through the vertebral bodies and the
      degenerated discs. In the case of a fracture, the instrumentation is made to
      withstand the bulk of the loads since the structural integrity of a motion
      segment may have been lost. This study was undertaken to evaluate the effect of
      different constructs on the stresses in Cotrel-Duboussett (C-D) pedicle (tulip)
      screws close to their junction with the rod bridging the motion segments to be
      immobilized. In order to minimize the effect of anatomical and material property
      variation between spines, adult porcine spines were used, thus providing a
      reproducible experimental model. Fresh 3-year-old porcine spines were potted in
      holders after the soft tissues were removed (with the exception of the
      ligamentous structures).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7819640
TI  - A biomechanical comparison evaluating the use of intermediate screws and cross
      linkage in lumbar pedicle fixation.
AB  - In lumbar fusion, controversy remains regarding the effectiveness of cross
      linking and the necessity of placing pedicle screws at the intermediate levels of
      the segment to be fused. The purpose of this study is to evaluate the stiffness
      of various rod/screw constructs used to instrument a three-level fusion with
      specific emphasis on the effect of cross-linking and the intermediate pedicle
      screws. Nine lumbar calf spines were mounted at L1 and L5. Pedicle screws (TSRH,
      Danek, Memphis, TN) were then placed bilaterally in the L2, L3, and L4 pedicles.
      Random sequence testing of the following constructs was then conducted: TSRH rods
      connected bilaterally to the L2 and L4 pedicles with and without a cross-link,
      and rods connected bilaterally at the L2, L3, and L4 levels with and without a
      cross-link. The tests were conducted on a modified MTS testing machine (MTS,
      Minneapolis, MN) and consisted of cyclic application of axial load, torsion, and
      flexion and extension. The tests yielded axial, sagittal, and torsional stiffness
      values. Statistical analysis was performed using log transformation and Fischer's
      test of least significant difference. In axial testing the use of additional
      screws in the intermediate pedicles increased stiffness an average of 160% (p =
      .007). The addition of a cross-link did not increase stiffness with axial
      loading. In flexion testing the six-screw construct was 84% stiffer when compared
      with the four-screw construct (p = 0.0001). There was no significant change in
      flexion stiffness with addition of cross-links. In torsional testing the six
      screw construct was 38% stiffer than the four-screw construct (p =
      0.042).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7819641
TI  - Lumbar diskectomy for recurrent disk herniation.
AB  - Eighty-two patients who underwent reoperation using a lumbar microdiskectomy
      approach for recurrent back and leg pain were evaluated retrospectively. Patients
      were entered consecutively except for exclusion of those who had a spinal fusion
      in addition to the diskectomy or those where a diskectomy was performed as an
      adjunct to decompression for spinal stenosis. As a percentage of all diskectomies
      performed by us over the 13 years of the study, the overall rate of reoperation
      (including all patients who underwent more than one diskectomy procedure
      regardless of vertebral level and side) was 7.4%, with those having a reoperation
      on the same level and either the same or contralateral side as the initial
      procedure representing 4.5%. Long-term outcomes obtained from 68 questionnaire
      responses (83% compliance) included 56% who had successful leg pain relief, 54%
      who had successful back pain relief, 44% who successfully returned to work, 51%
      who successfully returned to normal activity, and 73% who were satisfied with the
      results of surgery. Poor outcomes correlated most significantly with reoperation
      on the same vertebral level, same side, and short (< or = 1 year) time interval
      between consecutive diskectomies. A major conclusion was that workers'
      compensation patients presenting within 1 year with recurrent complaints after
      diskectomy and whose radiologic findings indicate a same-level, same-side
      recurrence represent extremely poor outcome risks for repeat diskectomy.

PMID- 7819642
TI  - Continuous motion analysis of the head-neck complex under impact.
AB  - The objective of the present study was to analyze the localized kinematic
      biodynamics of the human head-neck complex under impact loading. Unembalmed human
      cadaveric head-neck complexes were subjected to axial compressive forces
      delivered using an electrohydraulic testing device. The head-neck complex was
      aligned along the stiffest-axis; musculature was simulated using preloaded
      springs and cables; and retroreflective targets were inserted into the vertebral
      body, the facet joint articulation, and the spinous process at every level of the
      cervical column. At dynamic loading rates (1.8-5.1 m/min), mid to lower cervical
      spine injuries consistently occurred in these preparations. Continuous motion
      analysis of the components (vertebral body, intervertebral disk, facet joint, and
      the spinous process) at all levels of the cervical spine showed the temporal
      order of the transfer of the external load. Injuries documented by computed
      tomography and cryomicrotomy techniques correlated with the kinematics of the
      structure. The application of dynamic loading to the head-neck complex coupled
      with high-speed, continuous-motion analysis of the intervertebral components of
      the entire cervical column makes possible the definition of the temporal
      kinematic mechanics that are fundamental to the understanding of the biodynamics
      of cervical spine trauma. Using these procedures, we have correlated the
      kinematics with the onset and pattern of neck injury secondary to impact forces.

PMID- 7819643
TI  - Anatomical and morphometric studies in posterior cervical spinal screw-plate
      systems.
AB  - To study potential risks for complications in posterior articular pillar plate
      fixation, screw-plate systems of Roy-Camille, Louis, and Magerl were implanted
      into the cervical spines of cadavers under authentic operation theater conditions
      and in vitro into isolated spine specimens according to the inaugurators'
      recommendations with regard to plate and screw positioning. We compared these
      systems with the method of our preference, using the small AO compression plate
      and monitoring each screw insertion fluoroscopically. The screws were directed
      toward the projection of the pedicles, and their length was measured
      individually. Radiographic analysis of the specimens and cryoplaning after
      implant removal and casting of the screw-plate cavities showed significant
      differences of the four systems with respect to effective screw length, possible
      and desirable screw trajectories, and risk for injuries of the facet joints,
      foraminal neurovascular elements, and vertebral artery, as well as mechanical
      conflict of the plate with adjacent facet joints.

PMID- 7819644
TI  - Posterior decompression and fusion in rheumatoid disease of the cervical spine:
      redressing the balance.
AB  - Forty-seven patients with rheumatoid disease of the cervical spine were followed
      over an 8-year period. Twenty-one patients with isolated atlantoaxial subluxation
      and four with combined atlantoaxial and subaxial disease had their atlantoaxial
      instability treated by posterior decompression and fusion. The incidence of
      surgical mortality was 8%, and clinical improvement was noted in 75%. There was
      no neurological deterioration in those patients who survived long term. We have
      found posterior decompression and fusion to be a satisfactory procedure for the
      treatment of atlantooccipital subluxation. In our experience, anterior
      decompression has not been found necessary for successful treatment of
      atlantoaxial subluxation in patients with rheumatoid cervical spine disease.

PMID- 7819645
TI  - Giant sacral cysts with neurogenic bladder.
AB  - Most sacral cysts are accidentally found on lumbar myelograms and are usually
      asymptomatic. We operated on two patients with giant sacral cysts from S3 nerve
      roots who complained of neurogenic bladder and perianal sensory disturbance as
      well as buttock pain. Morphology of these cysts and intraoperative
      electrophysiological findings of nerve conduction block showed two kinds of
      pathogenesis causing these neurological symptoms. One was attributed to
      conduction block of more caudal sacral nerves squeezed between these giant sacral
      cysts and the other was due to degeneration of nerve root fibers involved in the
      sacral cyst walls. Postoperatively, buttock pain and perianal hypesthesia were
      resolved, but the neurogenic bladder showed only partial recovery.

PMID- 7819646
TI  - Thoracic epidural abscess.
AB  - Twenty-one cases of thoracic spinal epidural abscess occurring over a 10-year
      period were retrospectively reviewed. Diagnosis was made by MRI or myelography
      and confirmed in the operative cases. A bacterial agent was isolated in 18 of the
      cases (86%). When measured, the erythrocyte sedimentation rate was elevated in
      all cases. Four patients who presented without neurologic deficits remained
      intact. All patients who presented with neurological deficits underwent surgical
      intervention in addition to intravenous antibiotics. Of the 15 patients who
      presented with a paraparesis of less than antigravity strength, five eventually
      were independent ambulators and continent. A good outcome resulted in 80% of
      those who underwent decompression within 24 h, as opposed to only 10% of the
      patients decompressed after 24 h. Good results can be obtained despite severe
      neurologic compromise when treated by rapid diagnosis and decompression of the
      spinal canal.

PMID- 7819647
TI  - Hyperextension fracture-dislocation of the thoracic spine with paraplegia in a
      patient with diffuse idiopathic skeletal hyperostosis.
AB  - The case is described of a hyperextension thoracic spine fracture in a patient
      with diffuse idiopathic skeletal hyperostosis (DISH). A 70-year-old woman awoke
      paraplegic after retroperitoneal surgery after having been positioned in the
      hyperextended axially rotated position. Imaging demonstrated a T9-10 fracture
      dislocation with severe pressure on the spinal cord, as well as findings typical
      of DISH. This case emphasizes the danger inherent in manipulating the ankylosed
      hyperostotic spine. It is proposed that patients undergoing surgery in this
      position should be evaluated for DISH as an additional risk factor.

PMID- 7819648
TI  - Development of multiple herniae on the thoracic level in a 2-year period.

PMID- 7819649
TI  - Immunomodulatory effects and therapeutic potential of glutamine in the critically
      ill surgical patient.

PMID- 7819650
TI  - Diarrhea with enteral feeding: prospective reappraisal of putative causes.
AB  - Our objective was to test, in tube-fed patients whether treatment with
      antibiotics, the presence of hypoalbuminemia, or the use of hypertonic tube
      feeding is associated with a higher incidence of diarrhea; how often tube feeding
      actually causes diarrhea; and whether administration of a Lactobacillus
      preparation reduces the incidence of diarrhea. Our study design included a
      randomized, double-blind, placebo-controlled trial of patients on tube feeding
      for at least 5 days. Stool weights and clinical assessment of bowel function were
      used as outcome measures. Diarrhea was defined as > 200 g of stool, or three or
      more liquid stools, in any 24-h period. The tube feeding was considered
      responsible for diarrhea only when the latter resolved on discontinuation of the
      feeding. When diarrhea did not resolve, other causes were sought. Of 62 patients
      enrolled, 41 reached a trial end point. Of these, 34 completed 5 days of feeding
      without diarrhea, and 7 experienced diarrhea. Although diarrhea was associated
      with hypoalbuminemia and with protracted treatment with antibiotics, in only 1
      subject who had a history of gastric surgery was it caused by tube feeding. The
      other 6 cases of diarrhea were caused by factors other than tube feeding, mainly
      drugs administered through the tube. Lactobacillus treatment did not alter the
      risk of diarrhea. Diarrhea occurs more commonly in tube-fed patients who have low
      serum albumin levels and have been treated with antibiotics for long periods, but
      these associations are generally not causal. Hypertonic feeding formulas are not
      associated with increased risk of diarrhea. Most cases of diarrhea in tube-fed
      patients are caused by factors extraneous to the tube feeding.

PMID- 7819651
TI  - Negative catheter-tip culture and diagnosis of catheter-related bacteremia.
AB  - The accuracy of paired quantitative blood cultures (PQtBCs) collected in
      pediatric Isolator 1.5-ml tubes compared to central venous catheter (CVC) segment
      cultures (hub and tip) to diagnose catheter-related bacteremia (CRB) was
      evaluated in 58 bacteremic adult patients. The second aim of this study was to
      state precisely whether the tip or the hub (or both) of the infected device was
      the source of the bacteremia in case of significant results of PQtBC. Fifty-eight
      bacteremic patients with suspected CRB entered the study. In 52 patients, the
      diagnosis was obtained before CVC removal by PQtBC and was confirmed by CVC
      segment cultures: CRB in 30 patients, non-catheter-related bacteremia in 22
      patients. Six patients had CRB not found by PQtBC. 1) PQtBC is 83% sensitive,
      100% specific (negative predictive values 78%, positive predictive values 100%).
      2) Sixteen bacteremic patients had authentic hub-related bacteremia (positive hub
      culture associated with negative tip cultures). When CRB is suspected in
      bacteremic patients, a negative tip culture cannot exclude the diagnosis of CRB.
      In all cases, CVC tip culture must be associated either with PQtBC or with hub
      cultures.

PMID- 7819652
TI  - Branched-chain amino acid supplementation during 30-km competitive run: mood and
      cognitive performance.
AB  - It has been suggested that an elevated concentration of the neurotransmitter
      serotonin (5-hydroxytryptamine, 5-HT) in specific areas of the brain may
      contribute to the development of central/mental fatigue during and after
      sustained exercise. Supplementation with branched-chain amino acids (BCAAs)
      should prevent the exercise-induced increase in the plasma concentration ratio of
      free tryptophan to other large neutral amino acids (including BCAAs) and thereby
      prevent an elevation in the level of 5-HT in the brain. In this study, subjects
      were given either a mixture of BCAAs in a carbohydrate solution or a placebo
      drink that contained only carbohydrates during a 30-km cross-country race.
      Several tasks to measure cognitive performance were performed before and after
      the race. When subjects were supplied with BCAAs, their performance in the
      different parts of the color-word test (words, colors and color words) was
      improved by an average of 3-7% (p < 0.05) after exercise, whereas there was no
      difference in performance before and after exercise in the subjects who were
      given the placebo. Furthermore, the experimental group, supplied with BCAAs,
      maintained their performance in the shape-rotation and figure-identification
      tasks, whereas an impairment in performance in these tests by 25% (p < 0.05) and
      15% (p < 0.05), respectively, was found in the subjects who received the placebo.
      Thus, BCAA supplementation seemed to have an effect on the more complex tasks,
      whereas no effect could be detected on the less demanding tasks. However, an
      intake of BCAAs during exercise modified only slightly the exercise-induced
      changes in mood.

PMID- 7819653
TI  - Fuel utilization and glucose hyperalimentation after liver resection.
AB  - Clinical studies and experiments in rats were carried out to elucidate changes in
      fuel utilization after hepatectomy. In addition, the effect of glucose
      hyperalimentation on energy metabolism in the liver remnant was studied.
      Respiratory quotient (RQ) and substrate oxidation rate for fat and glucose were
      evaluated by indirect calorimetry in eight patients who had undergone liver
      resection. Patients had a reduced nonprotein RQ of approximately 0.85 and a
      reduced ratio of glucose to fat oxidation of approximately 2.0 on the 1st and 2nd
      postoperative days. After 80% hepatectomy, rats received either 30 kcal.kg-1.day
      1 (group 1) or 200 kcal.kg-1.day-1 (group 2) of glucose for 48 h. In both rat
      groups, hepatic mitochondrial ATP synthesis 12 and 24 h after hepatectomy was
      accelerated when palmitic acid was used as the substrate and suppressed when
      pyruvate was used compared with sham-operated groups. This suggests that the
      energy substrate of the remnant liver was principally fatty acids rather than
      glucose, which seems to occur also in humans. Hepatic energy charge was within
      normal limits in group 1 (0.862 +/- 0.008) but decreased significantly in group 2
      (0.818 +/- 0.006, p < 0.01) 12 h after hepatectomy. An abundance of glucose in
      the early postoperative period therefore caused a hepatic energy derangement by
      suppressing endogenous fat oxidation. This suppression was corroborated by the
      findings of lower immunoreactive glucagon and nonesterified fatty acid
      concentration in group 2. Therefore, glucose hyperalimentation in the early
      postoperative period after liver resection is not recommended.

PMID- 7819654
TI  - The role of nutritional support in the management of a high-output stoma.

PMID- 7819655
TI  - pH measurements as guide for establishing short-term postpyloric enteral access.
AB  - Standard antiulcer regimens that use agents such as intravenous ranitidine (50 mg
      every 8 h) and/or intragastric antacids (30 ml every 4 h) do not seem to preclude
      use of pH-sensing feeding tubes in our patient population. The cost of placement
      ($174/successful tube) compared favorably (3-79% less) with the cost of other
      placement methods used at our institution. Immediate establishment of postpyloric
      access by this method can decrease delays in instituting nutritional support.
      Moreover, in patients at increased risk for aspiration, e.g., those with altered
      mental status, postpyloric tube placement may be beneficial in reducing
      aspiration occurrence. The equipment is portable and easy to operate, and the
      placement technique can be easily learned and performed at bedside by nurses and
      physicians. Whereas we feel that the sensitivity and specificity for intestinal
      placement are not sufficient to preclude a confirmatory radiograph, the
      sensitivity and specificity for intragastric placement in our study were both
      100%. Our own policy is to obtain a confirmatory radiograph before institution of
      any nutritional therapy through a central access device (central venous catheter
      or feeding tube). However, depending on hospital or departmental policy, a
      radiograph may be unnecessary when intragastric placement is deemed adequate.
      Finally, this placement method may obviate the need for more intricate and
      expensive methods of feeding-tube placement.

PMID- 7819656
TI  - Malnutrition in the wards of the world.

PMID- 7819657
TI  - Catheter-related bloodstream infection: pathogenesis and diagnosis.

PMID- 7819658
TI  - Nutrition, cognitive performance, and mental fatigue.

PMID- 7819659
TI  - Generic enteral formulas ... a future trend?

PMID- 7819660
TI  - The endgame.

PMID- 7819662
TI  - Stratification and blocking.

PMID- 7819661
TI  - Are genetically engineered foods safe?

PMID- 7819663
TI  - Antioxidant vitamins and cancer risk.

PMID- 7819665
TI  - The skeleton in the hospital closet.

PMID- 7819664
TI  - The skeleton in the hospital closet. 1974.

PMID- 7819666
TI  - The Skeleton in the Hospital Closet--20 Years Late: Malnutrition in Patients with
      GI Disease, Cancer and AIDS. Los Angeles, California, October 1-2, 1994.
      Abstracts.

PMID- 7819667
TI  - [Trends in nursing care requirements in German 1990-2050--results of demographic
      projections].
AB  - Since the political agreement on the financing of elderly primary care, the
      question of the determinants for both the absolute number of elderly persons
      requiring care and the care burden is of particular importance. The probable
      demographic effects of a change in immigration and mortality rates in Germany are
      shown with the aid of various models. A higher life expectancy under the
      condition of a stable age-specific care quota leads to a substantial increase in
      the need for elderly care. Similarly, the future care burden will not remain
      stable with an increased immigration of young people; rather it will increase as
      well. It can thus be predicted that the problem of the care burden as well as its
      financing will remain an important topic in the future for demographic reasons
      alone.

PMID- 7819668
TI  - [The effects of the psychiatric personnel regulation on regional structures of
      psychiatric care].
AB  - The current structure of psychiatric treatment emphasizes inpatient care. When
      implemented, the Psychiatric Personnel Regulation (Psych-PV) will decisively
      influence the structure of services offered by complementary care facilities.
      Using the existing treatment capacity of a German city-state as an example, we
      illustrate the structural changes that implementation of the Regulation may be
      expected to produce and how they will affect complementary care. In particular,
      the emphasis placed on rehabilitation in inpatient care will produce a shift
      toward outpatient services.

PMID- 7819669
TI  - [Patient contact supported effectiveness evaluation of legal guidelines on
      ambulatory care].
AB  - A network of about 100 physicians (general practitioners, internists) has been
      introduced in Lower Saxony, Germany. The participating physicians report on a
      sample of their patient contacts involving frequent complaints (e.g. vertigo, leg
      problems, pain due to rheumatic conditions, and gastrointestinal disturbances).
      The project combines individual, problem-specific patient monitoring with the
      physicians' estimation of both the conditions under which they conduct their
      practice and the state of the regional health care system. A standardized
      questionnaire records sociodemographic variables and major reasons for the
      patients' visit. It also records data about diagnoses, diagnostic and therapeutic
      strategies and changes in therapy. In 1993 special attention was given to an
      assessment of recent health care cost containment legislation and its effects
      upon the quality of ambulatory medical care. 1400 patient contacts have been
      reported on in the first two surveys. Results are presented in this article.

PMID- 7819670
TI  - [Guidelines for social medicine assessment and evaluation of primary
      fibromyalgia].
AB  - Primary fibromyalgia belongs to the spectrum of rheumatic soft tissue disorders.
      It is characterized by wide-spread chronic pain and a low pain threshold. The
      etiology of the disorders is still unknown. Clinical diagnosis requires
      examination by a rheumatologically trained physician pathognomonic findings are
      largely lacking. Classification criteria have been published by Wolfe et al. on
      behalf of the American College of Rheumatology (ACR). The prognosis of FMA is
      unfavourable and does hardly, respond to therapy. FMA patients' work capacity
      cannot be established by mere diagnosis; individual impairments have to be taken
      into account: Clinical, psychosocial and behavioural dimensions have to be
      considered. Neither inpatient rehabilitation nor early retirement seem to
      significantly influence the course of FMA. The patient can usually work fulltime
      in jobs requiring light activities.

PMID- 7819671
TI  - [The epidemiologic significance of varicella].
AB  - A total of 552 persons working in the university hospital of Freiburg, Germany
      (nurses, pediatric nurses, administration--and technical personnel) was screened
      for antibodies to varicella zoster virus. Prevalence of antibodies to VZV among
      men was higher than among women. While the degree of immunity of nurses and
      administration/technical personnel was comparable, pediatric nurses had a
      significantly higher seroprevalence (< 20 years 89.3%, -30 years 95.7%, > 30
      years 98.6%). Therefore, pediatric nurses should be screened and susceptible
      persons should be vaccinated.

PMID- 7819672
TI  - [Immunity to diphtheria of African guest workers and students].
AB  - This study investigated the immuno-protective diphtheria antitoxin titres of 38
      guest workers from Mozambique and 44 students from Cameroon 18 to 35 years of
      age. Two methods were used to analyse the sera: the cell culture method and the
      indirect haemagglutination test. The results of both methods were comparable.
      Approximately 69% of the guest workers from Mozambique showed protective
      diphtheria antitoxin levels (> or = 0.1 IE/ml), 24% had a boosterrequiring basic
      immunity (> or = 0.01-0.09 IE/ml), whereas 7% showed no protective diphtheria
      antitoxin levels. This compared with 46, 35 and 19% respectively among the
      students from Cameroon.

PMID- 7819673
TI  - [The 1990 salmonella epidemic in the commercial city of Lubeck--an epidemiologic
      study as a contribution to determining the etiology of the salmonella outbreak].
AB  - In 1990 in Germany for the first time more than 100,000 cases of enteric
      infections (mostly salmonella enteritidis) were registered. The incidence is
      still increasing. As only one of ten cases is reported the yearly overall loss to
      general economy is estimated up to DM 600,000,000. Many hypotheses on causes were
      suggested but none could be verified (e.g. mass-breeding of animals, modernistic
      habits of eating and drinking, introduction of microwave-cooking, deterioration
      of hygiene in kitchens, insufficient cooling of food). This paper reports on the
      result of retrospective interviews with regard to food- and kitchen-hygiene of
      persons suffering from salmonellosis during an epidemy in Lubeck in autumn 1990.
      As no systematic violations of rules of hygiene could be detected we concluded
      that in future prevention and research should again be concentrated especially on
      the control of animal feed imports, poultry breeding, cooling and technical
      processing of eggs and garbage-sanitation. In Sweden consistent elimination of
      infected poultry stock showed effect. In the Federal Republic of Germany more
      drastic steps in regard of planed EC-Guidelines on the control of zoonoses are
      demanded.

PMID- 7819674
TI  - [The significance of AIDS for mortality in Berlin (West)].
AB  - Following a long-term decline, death rates due to infectious diseases in West
      Berlin men have dramatically increased since 1983. The Berlin mortality
      statistics introduced AIDS as a specific cause of death only in 1989. However,
      opportunistic infections, a negligible quantity until 1983, and pointing to AIDS
      as the underlying cause, show a steep increase in the mid and late eighties. In
      terms of Potential Years of Life Lost, AIDS-related mortality amounts to 8
      percent of total mortality in West-Berlin men in 1989/1990.

PMID- 7819675
TI  - [Female prostitution and HIV/AIDS--review of the literature on epidemiology and
      personal observations in a contact center for drug dependent patients].
AB  - Epidemiological studies show that intravenous drug use represents the main risk
      for HIV/AIDS infection among female prostitutes in Germany. According to current
      information, HIV/AIDS infections are not more prevalent among prostitutes who are
      not intravenous drug users than in the general population. To establish effective
      preventive measures against HIV/AIDS infection, we must differentiate between two
      specific target groups: 1) female intravenous drug users who engage in
      prostitution to finance their drug addiction, and 2) female prostitutes who are
      not intravenous drug users. Instead of mandatory health checks by government
      agencies, registered female prostitutes who rarely use intravenous drugs should
      be offered health counseling and care. Easily accessible offers in contact
      centers for intravenous drug users will help HIV/AIDS prophylactic programs to
      reach women who engage in illegal prostitution to finance their drug addiction.
      Secondary HIV/AIDS preventive measures at these centers include exchange of
      syringes and needles, distribution of condoms, initial contact with a drug
      counselor, treatment of acute medical problems, physician counseling services,
      and facilities for HIV testing. In addition to this, substitutive therapeutic
      regimens as alternatives to withdrawal therapy of drug addiction would contribute
      effectively to HIV/AIDS prevention, particularly for intravenous drug using
      female prostitutes who are HIV-infected and have discontinued withdrawal therapy.

PMID- 7819676
TI  - [Statistical description of health complaints after pyrethroid exposure].
AB  - In 96 pyrethroid-exposed persons data on subjective health impairment were
      collected by means of a questionnaire. The present explorative statistical
      analysis is restricted to a subgroup of 51 out of the 96 persons for which
      pyrethroid concentrations in dust samples from residential dwellings or from work
      places could be determined. Since measurements were taken from dwellings or work
      places, there is in some cases only one common measured value for families or
      teams. In total, we have 34 independent measurements. Based on the type of
      measured exposures, the 51 participants can be divided into 3 groups: 26 cases
      exposed to permethrin and tetramethrin (type-I pyrethroids), 13 cases exposed to
      deltamethrin, cyfluthrin or cypermethrin (type-II pyrethroids), and 12 cases with
      mixed exposure to the mentioned type-I and type-II pyrethroids. For the 3 groups
      we computed weighted mean values of pyrethroid concentrations, each independent
      measurement being weighted with the number of corresponding persons. The mean
      values are 425.7, 56.1, and 958.9 mg pyrethroid/kg dust for the groups in the
      above order. After combining the two highly exposed groups into one new group
      with now 38 members and a mean pyrethroid concentration of 594.1 mg/kg, an
      increased frequency of health complaints was found as compared to the group
      exposed only to type-II pyrethroids.

PMID- 7819677
TI  - [Chlorophenols in urine as an environmental medicine monitoring parameter].
AB  - Chlorophenols occur ubiquitously in the environment. They are taken up as such in
      man or are formed in intermediary metabolism e.g. from chlorobenzenes. In
      particular pentachlorophenol (PCP) is one of those chemical substances used up to
      the early 70's as a component of wood preservatives also indoors; for many years
      it has been at the centre of discussion about the environment. Mono, di, tri and
      tetrachlorophenols as well as pentachlorophenol occur in the urine in the general
      population often in surprisingly high concentrations. An increased chlorophenol
      excretion under certain circumstances also indicates an increased dioxin exposure
      (pre-dioxins). Possible sources of emission and routes of absorption for
      corresponding organochlorine compounds can be found in industry, agriculture and
      also private households. Environmental analysis in the air, in earth or dust do
      not allow any evaluation of health risks. Only biological monitoring with
      qualitative and quantitative determination of the actual concentration of the
      substance taken up by the organism allows a reliable estimation of the individual
      health risk. The background exposure of the general population not occupationally
      exposed to organochlorine compounds can be used for the determination of so
      called norm values. For the determination of the chlorophenol spectrum 50 ml
      urine are necessary. The following values can be given as reference values for
      the most important chlorophenols: 4-monochlorophenol: 7.5 micrograms/l, 2.4
      dichlorophenol and 2.5-dichlorophenol: 33.6 micrograms/l, 2.4.6-trichlorophenol:
      4.7 micrograms/l, 2.4.5-trichlorophenol: 4.5 micrograms/l, 2.3.4.6
      tetrachlorophenol and 2.3.5.6-tetrachlorophenol: 22.0 micrograms/l,
      pentachlorophenol 9.0 micrograms/l urine.

PMID- 7819678
TI  - [Providing medical care as a service--new aspects for quality assurance?].
AB  - The present article attempts to understand medical care as a service. It is not
      the doctor's work which is of primary interest for the demanding patient but the
      result of the treatment. Applied to the quality assurance in medicine this means
      that medical treatment as an integral whole and the patients' satisfaction have
      to be considered as a standard judgement to a greater extent than to date.

PMID- 7819679
TI  - [The federal emission control law/monitoring practice of applications by health
      offices].
AB  - In accordance with a directive of the office of the Regional Government in
      Darmstadt, magistrates and county boards are to be involved in approval
      proceedings under the Pollution Control Act. In these proceedings, the health
      offices review and comment on the individual projects. In many cases the scope of
      the health office review overlaps with that of other public authorities, since a
      precise definition of the public health tasks has been lacking to date. In
      consultation with concerned parties and the approval authority, the Task Force of
      Hessian Health Offices (Arbeitsgemeinschaft hessischer Gesundheitsamter) has
      addressed this issue in principle, and has discussed and established testing
      criteria. In this article, we use two examples of health office reviews to
      present our results. We hope that the article will stimulate an exchange of
      experience with other health offices.

PMID- 7819680
TI  - A sibship with recurrent Kawasaki disease and coronary artery lesion.
AB  - Although epidemiologic studies of Kawasaki disease suggest an infectious
      etiology, the cause of this mysterious disease remains unclear. We describe the
      occurrence of five episodes of Kawasaki disease over a six-year period in three
      siblings. Two of the three children experienced recurrent Kawasaki disease and
      developed coronary artery lesions, which included giant coronary artery aneurysms
      in the youngest child. The non-contemporaneous occurrence of the disease in these
      three children emphasizes the importance of a genetic basis and/or environmental
      factors in the etiology of Kawasaki disease.

PMID- 7819681
TI  - Sepsis, Salmonella and strategy.

PMID- 7819682
TI  - Cardiovascular changes during sustained lung inflations in premature newborn
      lambs.
AB  - We studied the effect of sustained inspiratory inflations (SI) on the
      cardiovascular system by measuring mean central venous pressure (MCVP), mean
      arterial blood pressure (MABP) and heart rate (HR), before and during sustained
      lung inflations in premature lambs (128-133 days' gestation). SI consisted of
      four inflations of 5 s at a peak inspiratory pressure of 35 cmH2O, with a mixture
      of 5% carbon dioxide and 95% oxygen. Each inflation was followed by a positive
      end-expiratory pressure of 5 cmH2O for 5 s. Percentage change from baseline was 
      3.88% for MABP and -2.55% for HR during the first inflation. The changes in MCVP
      fluctuated with each inflation (mean 9.61%; p < 0.01 versus baseline) and
      deflation (mean -3.87%; p < 0.05 versus baseline). These changes were dependent
      on the time after birth and the pressure used for SI. The observed cardiovascular
      changes produced by this procedure are considered clinically relevant when
      managing premature infants with a high risk of intraventricular haemorrhage.

PMID- 7819683
TI  - Airway and body surface sensors for triggering in neonatal ventilation.
AB  - Failure of neonatal patient triggered ventilation may reflect a delay in delivery
      of flow relative to the inspiratory effort of the infant. Transmission of
      diaphragmatic contraction to the sensor site (patient delay) and further
      transmission to and within the sensing device (device delay) both contribute to
      the delay in triggering. Patient and device delays were studied for different
      sensing systems in 36 infants, 24 of whom were intubated. Device delay was long
      (> 40 ms) with a conventional apnoea monitor compared with sensors placed at the
      airway opening (2 ms), the inspiratory (12 ms) and expiratory (3 ms) pressure
      transducers of the ventilator, the Graseby capsule (8 ms), strain gauges (3 ms)
      and oesophageal pressure (6 ms). In near normal infants, the sum of patient and
      device delays for the latter sensors was less than 20 ms and a minor component of
      the total delay. However, in severe lung disease the total delay may be more than
      100 ms even for airway sensors.

PMID- 7819684
TI  - Cerebral blood flow and plasma hypoxanthine in relation to surfactant treatment.
AB  - We have previously reported reduction in EEG activity in preterm babies after
      tracheal instillation of Curosurf. To elucidate the cause of EEG depression, we
      have examined cerebral blood flow (CFB), amplitude-integrated EEG (aEEG), mean
      arterial blood pressure (MABP) and plasma hypoxanthine (Hx) concentration in a
      group of preterm babies before and immediately after administration of
      surfactant. No change occurred in CBF immediately after surfactant treatment
      despite a significant decrease in MABP. At 60 min after surfactant
      administration, a significant reduction in CBF occurred (p < 0.05). However, when
      CBF values were corrected for changes in PaCO2, no reduction in CBF was observed.
      Mean plasma Hx concentration was 11.6 (SD 7.3) mumol/l before surfactant therapy,
      which decreased significantly to 8.1 (5.8) mumol/l (p < 0.05) 15-30 min after
      treatment. No correlations were found between plasma Hx concentration and FiO2,
      a/A pO2, PaCO2, SaO2, arterial blood pressure, CBF or the degree of EEG
      depression. This study indicates that EEG depression observed after surfactant
      instillation is not caused by cerebral ischemia.

PMID- 7819685
TI  - Inter-relationship between serum concentrations of glucose, glucagon and insulin
      during the first two days of life in healthy newborns.
AB  - The relationship between serum concentrations of glucose, insulin and glucagon
      during the first two days of life was studied in healthy newborns. The first
      capillary blood sample was obtained at 3-15 h of age (median 6 h; day 0) and a
      second sample approximately 24 h later (day 1). Serum glucose concentrations in
      the first sample averaged 2.1 +/- 0.07 mmol/l (mean +/- SEM; n = 60) and were
      positively correlated with postnatal age (p < 0.01). Serum glucagon
      concentrations in the first sample averaged 570 +/- 32 pg/ml and were inversely
      correlated with glucose concentrations (p < 0.0001). At the second sampling,
      serum glucose concentrations had increased to 2.9 +/- 0.07 mmol/l (p < 0.001; n =
      57) and serum glucagon concentrations had decreased to 403 +/- 22 pg/ml (p <
      0.001). Serum insulin concentrations were 11.7 +/- 0.3 microU/ml and 10.2 +/- 0.3
      microU/ml at the two samplings and did not correlate with serum glucose
      concentrations. The relationship of serum glucose and hormone concentrations to
      maternal and infant characteristics was studied by stepwise regression analysis.
      Serum glucose concentration on day 0 was positively correlated with postnatal age
      (p < 0.01) and birth weight (p < 0.05) but inversely correlated with duration of
      labour (p < 0.05). Serum glucose concentration on day 1 was positively correlated
      with birth weight (p < 0.0001) and inversely correlated with maternal prep
      pregnancy weight (p < 0.05). Similar analyses of serum hormone concentrations did
      not demonstrate any relationships with maternal or infant
      characteristics.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7819686
TI  - Lactate and pyruvate concentrations in capillary blood from newborns.
AB  - Using high pressure liquid chromatography on strong cation exchange column, we
      analyzed capillary blood from 141 healthy full-term newborns for lactate and
      pyruvate concentrations. Total range of lactate was 367-3245 mumol/l and
      reference interval (mean +/- 2 SD) was 260-2212 mumol/l. Total range of pyruvate
      was 10-141 mumol/l and reference interval (10th/90th percentile) was 12-71
      mumol/l.

PMID- 7819687
TI  - Prevention of neonatal infections by vaginal chlorhexidine disinfection during
      labour.
AB  - Comparison of two different methods of vaginal disinfection was made with regard
      to prevention of neonatal infections. In method I, an antepartum vaginal douche
      with a chlorhexidine solution was used; method II involved the use of
      chlorhexidine gluconate obstetrical gel during vaginal exploration. We studied
      2853 normal deliveries from a total number of 3236 deliveries: 1467 deliveries
      were allocated randomly to receive a vaginal douche whereas 1386 underwent
      vaginal exploration using chlorhexidine gel. A total of 203 neonates were
      transferred to the neonatal unit (120 males and 83 females): 101 belonged to the
      group where the mothers were subjected to method I, whereas in 102 method II had
      been used. Within 48 h postpartum 30 neonates from the method I group and 34
      neonates from the method II group received systemic antibiotics. There was a
      tendency towards a higher proportion of full-term neonates with verified
      septicaemia in the method II group (6 versus 2), whereas the numbers of probable
      infections were 8 versus 12. The corresponding total numbers in preterm infants
      were 3 and 2, respectively. These differences were not statistically significant.
      We conclude that the use of chlorhexidine douche compared with vaginal
      exploration with chlorhexidine gel provides no additional advantages.

PMID- 7819688
TI  - Neonatal Ureaplasma urealyticum colonization and chronic lung disease.
AB  - We studied Ureaplasma urealyticum colonization in 93 intubated infants
      (gestational ages 23-40 weeks) in our neonatal intensive care unit by obtaining
      cultures from endotracheal aspirate and nasopharynx during their first week of
      life. Eighteen infants had positive cultures, giving a colonization rate of 19%.
      No infant more than 30 weeks' gestation had a positive culture. The infants with
      positive cultures had a significantly lower gestational age and birth weight (p <
      0.009 and p < 0.005), with a colonization rate of 33% in infants less than 1000
      g. Among the infants with positive cultures, 10 of 17 developed chronic lung
      disease in contrast with 21 of 72 infants with negative cultures. The development
      of chronic lung disease and duration of oxygen requirement was strongly
      associated with immaturity but only weakly with Ureaplasma urealyticum.

PMID- 7819689
TI  - Chronic childhood idiopathic thrombocytopenia purpura: long-term follow-up.
AB  - An understanding of the natural history of childhood chronic idiopathic
      thrombocytopenia purpura (ITP) could contribute to a rational therapeutic
      approach to its treatment, which remains controversial. In our retrospective
      study of 92 children with ITP, 22 had a chronic course and were followed for 3-14
      years (median 8.6 years). Treatment, when indicated, was individualized: 4
      patients (18.2%) did not receive any treatment, 14 (63.6%) received steroids
      only, while 4 (18.2%) were treated with steroids and one of the following: high
      dose gamma globulin (4 patients), splenectomy (2 patients) or immunosuppressive
      therapy (2 patients). During follow-up, 14 patients (63.6%) achieved complete
      remission, 5 (22.7%) partial remission and only 3 (13.5%) remained severely
      thrombocytopenic, with minimal bleeding tendency. Eleven patients (50%) responded
      to the initial prednisone course (1-5 mg/kg/day), but showed a marked decrease in
      platelet count when steroids were tapered off. In view of the high rates of
      complete and partial remission and the mild course of the few non-responding
      patients, it is suggested that with adequate supportive therapy, follow-up
      problems and fatalities can be kept to a minimum. We believe that aggressive
      therapy, such as splenectomy, should be reserved for the rare symptomatic and
      severely thrombocytopenic patient.

PMID- 7819690
TI  - Clustering of risk factors for coronary heart disease in children and
      adolescents. The Cardiovascular Risk in Young Finns Study.
AB  - Clustering of selected coronary heart disease (CHD) risk factors was studied in a
      cohort of 3457 children and adolescents, aged 3-18 years. Subjects were defined
      as "high-risk" individuals if their values for serum LDL cholesterol, systolic
      blood pressure and obesity index (sum of biceps, triceps and subscapular
      skinfolds) exceeded the age- and gender-specific 75th percentile of the present
      study cohort. Clustering was studied by using the observed/expected ratio (O/E
      ratio). Statistically significant clustering was observed as 3.1% of all subjects
      belonged to the high-risk group (O/E ratio = 2.0, p < 0.001). Under the
      assumption of no association, only 1.56% would have been expected. Clustering was
      stronger in boys (3.6%) than in girls (2.6%). When other lipid variables (total
      cholesterol, HDL cholesterol, triglycerides) or obesity indices (subscapular,
      biceps, triceps skinfolds, the subscapular/triceps ratio and BMI) were used in
      the analyses, the degree of clustering remained essentially the same. The
      tendency of risk factors to cluster increased with age in boys, whereas in girls
      the strongest clustering was usually seen in the age group 9-12 years. When a
      fourth risk factor (low HDL cholesterol) was added to the analyses, the tendency
      of risk factors to occur simultaneously became even greater. Aggregation of
      multiple risk factors was strongest in boys who presented the highest levels of
      these risk factors. Common risk factors for CHD cluster in children and
      adolescents. The gender differences observed here may partly explain why males
      develop CHD more often than females in adulthood.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7819691
TI  - Waist measurement correlates to a potentially atherogenic lipoprotein profile in
      obese 12-14-year-old children.
AB  - Epidemiological studies have indicated a relationship between overweight and
      cardiovascular disease. The present investigation was undertaken to identify
      anthropometric variables in childhood which may reflect the risk of
      cardiovascular disease in terms of unfavourable changes in apolipoprotein and
      lipid concentrations. Twenty-nine obese 14-year-olds and 32 obese 12-year-olds
      were recruited from a school screening programme and anthropometric data
      reflecting overweight and fat distribution were subjected to analysis of
      covariance, with blood pressure, apolipoprotein and lipid concentrations as
      dependent variables. Results from the two groups were adjusted for puberty,
      gender and screening group, allowing pooling of data. After such an adjustment,
      waist circumference was significantly correlated (r = partial correlation
      coefficient) to high density lipoprotein (HDL) cholesterol (r = -0.08, p < 0.05)
      and triglycerides (r = +0.24, p < 0.01). The waist:hip ratio was significantly
      correlated to HDL-cholesterol (r = -0.10, p < 0.01) and triglycerides (r = +0.22,
      p < 0.01). BMI was significantly correlated to triglycerides (r = +0.25, p <
      0.001), and diastolic blood pressure (r = +0.08, p < 0.05). The partial
      regression coefficients for waist circumference versus apolipoprotein B (r =
      +0.07) and the apolipoprotein B:A-I ratio (r = +0.06) were as strong as those for
      waist:hip ratio (r = +0.03 and r = +0.05, respectively). Our results demonstrate
      that abdominal obesity is associated with an unfavourable lipid profile in obese
      12-14-year-old children. This may be related to an increased cardiovascular risk
      later in life. The waist measurement appears to be a convenient and informative
      anthropometric indicator of such metabolic alterations.

PMID- 7819692
TI  - Differentiation of glomerular and non-glomerular hematuria in children by
      measurement of mean corpuscular volume of urinary red cells using a semi
      automated cell counter.
AB  - Urine samples from 110 children and adolescents with micro- or macrohematuria
      were compared using phase-contrast microscopy and a semi-automated cell counter
      to differentiate glomerular from non-glomerular hematuria. Glomerular hematuria,
      defined by clinical criteria from biopsy and standard chemical evaluation, was
      observed in 73 patients (group 1): non-glomerular hematuria was found in 37
      patients (group 2). The latter group underwent urological operation and had
      normal urine before operation. Mean corpuscular erythrocyte volume (MCVU) and
      percent of dysmorphic erythrocytes were determinated. To exclude the influence of
      mean erythrocyte volume of blood erythrocytes (MCVB), MCVB was determined and
      additionally the quotient of MCVU/MCVB was calculated (MCVUB). The percentage of
      dysmorphic erythrocytes differed significantly between the two groups ((75 +/-
      13% in group 1 versus 38 +/- 27% in group 2 (mean +/- SD); p < 0.01), MCVU (34.0
      +/- 11.1 fl in group 1 versus 55.5 +/- 16.3 fl in group 2; p < 0.01) and MCVUB
      (0.41 +/- 0.14 in group 1 versus 0.67 +/- 0.20 in group 2; p < 0.01). When
      glomerular hematuria was defined on the basis of more than 80% dysmorphic
      erythrocytes, the sensitivity of phase-contrast microscopy was 0.52, specificity
      versus 0.96 and efficiency 0.64. When glomerular hematuria was defined as < 50 fl
      MCVU, sensitivity was 0.92, specificity 0.57 and efficiency 0.80 and as < 0.06
      MCVUB, sensitivity was 0.89, specificity 0.62 and efficiency 0.80. The
      correlation coefficient between MCVU and dysmorphic erythrocytes was -0.71 (p <
      0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7819693
TI  - Urinary incontinence and nocturia in healthy schoolchildren.
AB  - A frequency/volume chart was used to investigate the micturition pattern of
      healthy schoolchildren, aged 7-15 years. Of 242 objectively and subjectively
      healthy children, incontinence was recorded by 36 (14.9%). Nocturnal enuresis,
      defined as at least one wet night in three months, occurred in 19 (7.9%) children
      and daytime incontinence occurred with the same frequency. Four girls had both
      symptoms. Twenty-seven (11.2%) children woke up to void during the night of the
      investigation but habitual nocturia was established for only 4.1%. There was no
      difference in the micturition pattern between continent and incontinent children,
      and there was no correlation between incontinence, nocturnal micturitions and
      recorded oral fluid intake. At a follow-up one year later, using a questionnaire
      administrated to the same children, a persistent high rate of incontinence
      confirmed the original findings.

PMID- 7819694
TI  - Anorexia nervosa: who sees the patients and who do the patients see?
AB  - Two samples of patients with DSM-III-R anorexia nervosa, one identified by
      screening of a total population cohort and the other a mixed screening and
      referral group, were contrasted with a comparison group of sex-, age- and school
      matched individuals. The rates and types of services consulted and treatment
      given were analyzed. The groups with anorexia nervosa tended to differ somewhat
      in these respects, although the numbers were too small for meaningful statistical
      calculations to be made. Only half of the total population sample had ever
      received any treatment for the eating disorder, even many years after anorexia
      nervosa onset in the teenage period. The implications of these findings are
      discussed both in terms of clinical needs and as they relate to previous research
      in anorexia nervosa, which has almost exclusively referred to non-population
      based groups of patient.

PMID- 7819695
TI  - Peritoneal dialysis treatment in children and parental stress.
AB  - The burden placed on the parents of a child in dialysis treatment can induce
      negative effects on the medical treatment and on the psychological development of
      the child. To identify which families are at risk, both parents of 14 out of 16
      eligible patients in continuous ambulatory peritoneal dialysis (CAPD) answered an
      extensive questionnaire three times during one year. Large differences were found
      between the families with regard to the amount of stress experienced. Parents of
      older children (> 5 years) (and particularly parents of children with a failed
      transplantation) experienced significantly more stress. The nature of the stress
      was determined more by the psychological aspects than by the medical aspects of
      the treatment. Concern about the future contributed most to the stress
      experienced. Therefore, emotional support as well as practical help for families
      at risk is recommended.

PMID- 7819696
TI  - Infant survival in Norway and Sweden 1985-88.
AB  - In recent years, considerable attention has been attached to the disquieting fact
      that infant survival is much lower in Norway than in Sweden. In the present
      study, comprising all live single births in Norway and Sweden during 1985-88, the
      observed infant mortality was 1.5 times higher in Norway than in Sweden. The
      largest difference between Norway and Sweden was found in infants of young
      mothers with high birth order. Thus for the second births of mothers aged less
      than 20 years the observed mortality ratio of Norway to Sweden was 1.8. The
      infant mortality ratio decreased with increasing maternal age for all birth
      orders, and for the second births of mothers aged 35 years or more the mortality
      ratio was 1.0. The higher infant mortality in Norway was evident throughout the
      first year of life, with the highest mortality ratio observed at 6-8 months of
      life. Adjustment for maternal age, birth order and geographical region did not
      alter the observed infant mortality ratios. In both countries, the highest risk
      was found among infants of young mothers. this suggests a need for a more
      extensive preventive health care system directed at young mothers during their
      pregnancy and the infancy period.

PMID- 7819697
TI  - Hydrops foetalis and chylothorax associated with superior caval vein obstruction
      and resolution following balloon dilatation.
AB  - A female infant (33 weeks' gestation) was delivered by emergency caesarean
      section because of hydrops foetalis. No cause was identified initially;
      haemoglobin, liver and renal functions were normal and there was no evidence of
      sepsis or significant myocardial dysfunction or arrhythmia. There was initial
      improvement with conventional management but bilateral pleural effusions
      persisted, which became overtly chylous after institution of enteral formula
      feeds on day 4. At 5 weeks of age, an obstruction at the superior caval
      vein/right atrial junction was confirmed at angiography and dilated with
      resolution of all remaining oedema and fluid collections. Repeat venography at 9
      months of age showed a normal superior caval vein and she remains well at 15
      months.

PMID- 7819698
TI  - Variable outcome of a congenital cytomegalovirus infection in a quadruplet after
      primary infection of the mother during pregnancy.
AB  - A congenital cytomegalovirus (CMV) infection in a quadruplet has not been
      reported previously in the literature. We describe a congenital CMV infection in
      a quadruplet after primary CMV infection of the mother during pregnancy. One
      infant died antenatally, while another had cholestatic jaundice at birth and died
      of liver failure at three months of age. Of the two surviving infants, one showed
      no signs or symptoms of congenital CMV infection at 18 months of age, whereas the
      other had hearing loss and delayed development. CMV cultures of urine were
      positive at six weeks of age in all three infants born alive. The diagnosis of
      congenital CMV infection after primary CMV infection of the mother during
      pregnancy was made retrospectively by detection of CMV-immediate early antigen in
      three placentas as well as by examination of serum obtained from the mother
      during pregnancy.

PMID- 7819699
TI  - Enterobacter cloacae causing pneumatocele in a neonate.
AB  - Pneumatocele formation, a cyst-like rarefaction that develops within the lung
      parenchyma, is an unusual complication of pneumonia in the neonate. It has been
      reported to occur with Staphlococcus aureus, Escherichia coli, Klebsiella
      pneumoniae, Streptococcus pneumoniae, and Pseudomonas aeruginosa infections. We
      describe a case of a premature neonate with pneumonia and subsequent pneumatocele
      formation caused by Enterobacter cloacae.

PMID- 7819700
TI  - Salmonella enteritidis orchitis in a 10-week-old boy.
AB  - Extraintestinal manifestations of salmonellosis in paediatric patients are found
      predominantly in infants less than three months of age. Genital involvement is a
      rare complication. We present a short review of the literature and describe the
      case of a 10-week-old boy suffering from severe diarrhoea, who presented with a
      swelling of the right testicle after six days of illness. He underwent surgery on
      suspicion of testicular torsion, whereby orchitis was diagnosed. Salmonella
      enteritidis was cultured from the intraoperative swab. All cultures from blood,
      CSF and urine remained sterile. We conclude that orchitis must be taken into
      consideration as an extraintestinal complication of enteric salmonellosis and as
      a differential diagnosis of testicular torsion. In addition, we wish to emphasize
      that any infant less than three months of age with suspected or proven
      salmonellosis, should receive early antibiotic treatment.

PMID- 7819701
TI  - Hazards of ketoconazole therapy in testotoxicosis.
AB  - An eight-year-old boy with Leydig cell hyperplasia (testotoxicosis) was admitted
      with a three-day history of rash, vomiting and diarrhoea, followed by acute onset
      of breathlessness and confusion. He was shocked, with liver cell and renal
      failure, erythematous rash and severe interstitial pneumonitis. He had been
      treated with ketoconazole for four years prior to admission, receiving 1200mg
      daily during the preceding year. Cessation of ketoconazole therapy was associated
      with full clinical recovery but relapse of testotoxicosis. Ketoconazole was
      reintroduced cautiously at a lower dose, with no ill-effect, and reasonable
      control of testotoxicosis. We conclude that this boy's illness, including the
      interstitial pneumonitis, represented a reaction to ketoconazole which was dose
      related rather than idiosyncratic.

PMID- 7819702
TI  - Transient renal artery stenosis in infants: myth or reality?
AB  - We describe two infants with bilateral renal artery stenoses and severe
      hypertension. Adequate control of blood pressure was achieved by medical
      management. Endoluminal balloon dilatation of the renal arteries had been
      deferred because of their small size. On follow-up it was noticed that blood
      pressure had become progressively easier to control, with lesser amounts of
      antihypertensive medication. In fact, medication could be completely discontinued
      and blood pressure remained normal. On repeat arteriogram, bilateral renal artery
      stenoses had almost resolved in both patients. The etiology of the stenoses was
      not established in these patients. However, regardless of etiology, the transient
      nature of hypertension and renal artery stenoses in these two cases demonstrates
      that patient medical management of hypertension in infants can be a valid
      therapeutic option and occasionally obviate the need for unnecessary risky
      procedures.

PMID- 7819703
TI  - Effect of chlamydial antibodies on the outcome of in vitro fertilization (IVF)
      treatment.
AB  - OBJECTIVE: Our objective was to study the relationship between the presence of
      Chlamydia trachomatis antibodies and the success of IVF treatment. DESIGN: We
      evaluated 118 in vitro fertilization and embryo transfer (IVF-ET) treatment
      cycles from 51 couples with a history of infertility lasting for at least 2
      years. All women starting a treatment cycle had their serum chlamydial antibody
      titers measured by indirect immunofluorescent technique. All patients received
      similar ovarian stimulation regimens and the oocytes collected were inseminated
      with similar concentrations of motile sperm. Clinical data from couples where the
      female partner had C. trachomatis ab titers > or = 40 have been compared with the
      equivalent data from couples where the female partner had C. trachomatis ab
      titers < 40. RESULTS: There was no statistically significant difference between
      the two groups concerning age, infertility period, oocytes collected, oocytes
      fertilized, and fertilization rate, and the pregnancy rates were comparable.
      CONCLUSION: Previous exposure to C. trachomatis did not alter the success rate of
      IVF-ET.

PMID- 7819704
TI  - Hydatidiform mole with a coexistent fetus after ovulation induction.

PMID- 7819705
TI  - A plea for a more fastidious and objective use of statistics.

PMID- 7819706
TI  - Prospective randomized comparison of human chorionic gonadotropin versus
      intramuscular progesterone for luteal-phase support in assisted reproduction.
AB  - OBJECTIVE: The purpose of the study was to determine the impact of two forms of
      luteal-phase supplementation, human chorionic gonadotropin (hCG) and progesterone
      (P), during gonadotropin releasing hormone agonist (GnRh-a)/controlled ovarian
      hyperstimulation (COH) cycles. DESIGN AND PATIENTS: The study was a prospective,
      randomized evaluation of 77 patients. Group 1 patients (n = 38) received 2000 IU
      of hCG, injected subcutaneously, on days 3, 6, 9, and 12 after transvaginal
      aspiration of the oocytes (TVA = day 0). Group 2 patients (n = 39) received 50-mg
      daily injections of intramuscular (i.m.) P from days 2 to 14 after TVA. Blood
      tests were performed on days 0, 5, 8, and 12 after TVA. SETTING: The in vitro
      fertilization program of a tertiary care institution was the study setting. MAIN
      OUTCOME MEASURES: The main outcome measures were (1) pregnancy and implantation
      rates; (2) serum estradiol (E), P, and hCG levels; and (3) occurrence of side
      effects. RESULTS: Clinical pregnancy and implantation rates in group 1 versus
      group 2 were similar (36.7 vs 35.3 and 12 vs 14%, respectively). Regardless of
      pregnancy occurrence, on days 8 and 12 after TVA, serum E and P levels were
      higher in group 1 than group 2 but the resulting E/P ratios were similar. Five of
      38 patients (group 1) developed moderate to severe ovarian hyperstimulation
      syndrome (OHSS) right after the first or second supplementary hCG injection. In
      these patients, the mean serum E level on the day of hCG trigger injection was
      about 3250 pg/ml and the number of follicles was between 9 and 17. In 6 of 39
      patients (group 2) allergic reactions were observed at the P injection sites.
      CONCLUSIONS: Based on our data, hCG administration as a form of luteal
      supplementation did not translate, in comparison to P, into significant benefits
      for the patients. At the same time, it significantly increased the risk of
      ovarian hyperstimulation. We suggest that whenever, during COH cycles, serum E
      levels are over 2500 pg/ml and the number of follicles exceeds 10, luteal support
      with hCG should be excluded.

PMID- 7819707
TI  - Evaluation of two gonadotropin-releasing hormone (GnRH) analogues (leuprolide and
      buserelin) in short and long protocols for assisted reproduction techniques.
AB  - PURPOSE: The administration of two GnRH analogues (buserelin and leuprolide
      acetate) in long and short protocols was evaluated prospectively. In the long
      protocol, the analogues were given from day 1 of the cycle for at least 14 days
      and then hMG administration was started, while in the short protocol the
      analogues were initiated from cycle day 1, adding hMG from day 3. The patients
      were divided into four groups according to the protocol used: Group I, buserelin
      long; Group II, buserelin-short; Group III, leuprolide-long; and Group IV,
      leuprolide-short. Serum E2 levels on the day of hCG injection and the number of
      follicles observed, oocytes retrieved, and embryos obtained, as well as
      implantation rates, were significantly higher (P < 0.001) in the long protocols
      than in the short ones. RESULTS: Pregnancy rates were similar in all groups,
      although a trend for better results was observed in buserelin-long compared to
      buserelin-short. There were no differences in the results achieved with buserelin
      or leuprolide. CONCLUSION: The administration of GnRH analogues (buserelin and
      leuprolide acetate) in long protocols induced a more intense ovarian response and
      was associated with significantly higher implantation rates and also a trend for
      higher pregnancy rates, although this difference was not statistically
      significant.

PMID- 7819708
TI  - Three hundred cycles of oocyte donation at the University of Southern California:
      assessing the effect of age and infertility diagnosis on pregnancy and
      implantation rates.
AB  - PURPOSE: Our purpose was to evaluate the effect of age on endometrial receptivity
      and to compare success rates for oocyte donation among groups with differing
      primary diagnoses. DESIGN: This was a retrospective analysis of 300 consecutively
      attempted oocyte donation cycles. SETTING: The setting was the in vitro
      fertilization program at the University of Southern California. METHODS:
      Recipients were divided into groups according to age: Group I, < 30 years (n =
      8); Group II, 30-39 years (n = 59); Group III, 40-49 years (n = 107); and Group
      IV, 50-59 years (n = 18). Additionally, indications for treatment were divided
      into Classes A-G according to a primary diagnosis given to each patient and
      included premature ovarian failure (n = 44), surgical castration (n = 9), genetic
      disease carrier (n = 12), transitional menopause (n = 27), natural menopause (n =
      30), multiple IVF failures (n = 62), and postchemotherapy (n = 8). Recipients
      received oral micronized estradiol and intramuscular progesterone. Oocytes were
      donated by fertile young women utilizing ovarian hyperstimulation with menopausal
      gonadotropins. RESULTS: There were no significant differences among groups or
      classes related to either the number of oocytes received or the number of embryos
      transferred per cycle. Rates for embryo implantation and resorption and the
      clinical and ongoing or delivered pregnancy rates were similarly not different
      among patients except for women who previously received chemotherapy, where a
      significantly elevated rate of spontaneous abortion was noted P < 0.05).
      CONCLUSIONS: The establishment of pregnancy utilizing oocyte donation is not
      adversely affected by the chronological age of the recipient, inferring that the
      age-related decline in fertility is due primarily to oocyte aging, and not to
      loss of endometrial receptivity. Also, prior exposure to chemotherapy may alter
      endometrial integrity and lead to greater pregnancy wastage in women receiving
      donated embryos.

PMID- 7819709
TI  - Sperm:oocyte ratios in an in vitro fertilization (IVF) program.
AB  - PURPOSE: During the past few years, many oocyte insemination techniques,
      including microinjection, have evolved in the treatment of male-factor
      infertility. This preliminary study was designed to evaluate whether microdroplet
      insemination could be considered a reliable technique, especially for semen
      samples with male-factor defects. The first objective was to assess fertilization
      rates obtained by inseminating sibling oocytes using both the conventional IVF
      and the microdroplet method (Group 1). The second objective was to evaluate
      subsequent embryo development and pregnancy rates resulting from microdroplet
      insemination, in addition to formulating adequate sperm:oocyte ratios for various
      semen categories (Group 2). Four semen categories were studied including fresh
      normal sperm, frozen/thawed normal sperm, and male-factor sperm with one defect
      and two or three defects. RESULTS: Group 1 consisted of 54 couples; no
      statistical significance was found in the fertilization rates between test tube
      and microdroplet insemination in all four semen categories. Based on these
      results, patients from Group 2 (48 couples) had their oocytes inseminated only in
      microdroplets with sperm:oocyte ratios ranging from 2000 to 10,000 motile sperm:1
      oocyte. The average fertilization rate for male-factor sperm was 55%, with a 91%
      cleavage rate. CONCLUSION: Higher fertilization rates were observed in the lowest
      range of sperm:oocyte ratios (2000-4000:1) for male-factor sperm with one defect
      and in the highest range (8000-10,000:1) for male-factor sperm with two or three
      defects. Polyspermy occurred in only 0.4% of the oocytes inseminated.
      Microdroplet insemination is an alternative treatment for moderate to moderately
      severe male-factor infertility, establishing a bridge between conventional IVF
      and microinjection. With adequate sperm:oocyte ratios, this technique allows the
      natural selection process of fertilization in vitro to take place, without the
      high incidence of polyspermy or mechanical damage frequently observed in assisted
      fertilization techniques.

PMID- 7819710
TI  - Multiple scientific publications.

PMID- 7819711
TI  - Lipoprotein(a): new insights into an atherogenic lipoprotein.
AB  - Lipoprotein(a) constitutes a macromolecular complex in human plasma that combines
      structural features from the blood clotting and the lipoprotein systems. Aside
      from the discovery of lipoprotein(a) [Lp(a)] as a potential independent risk
      factor for premature cardiovascular disease its physiological role and activity
      remains obscure. Since the site of catabolism has not yet been fully
      characterized, there is intensive search for factors which influence plasma Lp(a)
      levels. Several clinical conditions and metabolic states have been identified to
      be added to the disorders of the lipid metabolism itself that modulate Lp(a)
      plasma levels. Diseases of the kidney and their accompanying factors (proteinuria
      and nephrotic syndrome) as well as end-stage renal disease and their treatment
      modalities (hemodialysis, peritoneal dialysis, and kidney transplantation) have
      all been found to increase Lp(a) plasma levels substantially. Fluctuations in
      Lp(a) also seem to occur in states of hormonal changes, such as in diabetes
      mellitus, after estrogen treatment, and during pregnancy. Recently a plausible
      mechanism for the atherogenic activity of Lp(a) has been ascribed to the
      inhibiting effect of Lp(a) on plasminogen activation, thus decreasing plasmin
      formation which in turn reduces the activation of transforming growth factor
      beta, a potent inhibitor of smooth muscle cell proliferation. Lp(a) exerts its
      pathological effect at plasma levels in the range of 20-30 mg/dl. Therefore, it
      seems mandatory to quantitate Lp(a) levels in patients who are at risk of
      developing progressive atherosclerotic disease to identify those with high levels
      of this unique atherogenic lipoprotein.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7819713
TI  - Elevated endothelin levels in patients with hyperlipoproteinemia.
AB  - We determined lipoproteins, apolipoproteins, and endothelin in 98 patients (58
      female and 40 male, age 18-72 years) with hyperlipidemia (plasma cholesterol >
      2.5 g/l and/or triglycerides > 2.0 g/l) and in 50 healthy subjects (20 female, 30
      male, age 19-68 years). In patients with hyperlipidemia endothelin levels were
      elevated compared to healthy controls. Patients with plasma cholesterol above 2.5
      g/l had higher endothelin and lipoprotein(a) concentrations than patients with
      plasma cholesterol levels less than 2.5 g/l. A positive correlation was found
      between the concentrations of endothelin and apolipoprotein B (r = 0.2137; P <
      0.013). Smoking patients with lipoprotein (a) above 300 mg/l had higher
      endothelin levels than both nonsmoking patients with lipoprotein (a) above 300
      mg/l and smokers with normal lipoprotein(a). In smokers endothelin correlated
      positively with Lp(a) (r = 0.709; P < 0.01). No correlation was found between
      endothelin and triglycerides nor between endothelin and age or sex. The results
      suggest that the vasoconstrictor endothelin contributes to the increased vasal
      tone in hyperlipidemia. Because endothelin also has mitogenic properties, it may
      play a relevant role in the development of premature atherosclerosis in patients
      with hyperlipidemia.

PMID- 7819712
TI  - Metabolism of energy-yielding substrates in patients with liver cirrhosis.

PMID- 7819714
TI  - Influence of selective management on the prognosis and the risk of rupture of
      abdominal aortic aneurysms.
AB  - A total of 199 patients with abdominal aortic aneurysms were followed up to
      investigate the influence of selective management on the prognosis and the risk
      rupture of abdominal aortic aneurysms. Decisions to operate or to continue
      watchful waiting with treatment of risk factors for expansion were based on
      aneurysm size, expansion rate, aneurysm-related symptoms, and individual
      operative risk. Rupture occurred in eight cases. All aneurysms were larger than 5
      cm, and six were larger than 6 cm in diameter at the last measurement before
      rupture. The resulting overall 5-year cumulative rate of rupture was 7.3% (Kaplan
      Meier). The 134 patients who underwent more than one ultrasound examination were
      observed for an average of 4.0 years (536 patient-years). The expansion rate was
      significantly correlated with the initial diameter and the diastolic blood
      pressure (best subset multiple regression analysis: r = 0.403; P < 0.001). A
      correlation with the systolic blood pressure was found only in univariate
      analysis (r = 0.236; P = 0.011). Amplitude of blood pressure, serum cholesterol
      level, low-density and high-density lipoproteins, ratio of low- to high-density
      lipoproteins age, and the extent of smoking habits were not correlated with the
      expansion rate. Our conclusion is that larger diameter and higher diastolic blood
      pressure are important risk factors for expansion of abdominal aortic aneurysms.
      Selective management of abdominal aortic aneurysms based on aneurysmal size,
      expansion rate, and patient characteristics may result in a low rate of rupture.

PMID- 7819715
TI  - A prospective evaluation of sensitivity and specificity of the ankle/brachial
      index in the follow-up of superficial femoral artery occlusions treated by
      angioplasty.
AB  - The aim of this study was to provide estimates of sensitivity and specificity of
      clinical history, pulses, and ankle/brachial index (ABI) in the follow-up of
      atherosclerotic occlusions of the superficial femoral artery treated by
      peripheral transluminal angioplasty (PTA). A total of 116 patients were followed
      prospectively for 1 year after angioplasty with follow-up visits immediately
      after angioplasty, and at 3, 6, and 12 months. All patients underwent digital
      subtraction angiography after 1 year of if they reported a deterioration of their
      symptoms. Reobstruction was defined as reocclusion or as restenosis exceeding
      70%. Patency rates were calculated separately by clinical and ankle/brachial
      criteria; sensitivity and specificity were derived using angiography as standard.
      The presence or absence of pulses distal to the treated vessel segment had a
      sensitivity of 78% and a specificity of 66% for a reocclusion or significant
      restenosis; subjective complaints evaluated by history had a sensitivity of 83%
      and a specificity of 51%. The sensitivity of the ABI was 72% and 66%, with a
      specificity of 82% and 100% for cutoff values of 0.10 and 0.15, respectively. One
      year after PTA the angiographic patency rate was 39% +/- 5%; the patency rate
      based on ABI criteria 34% +/- 5%. A deterioration in the ABI by 0.15 indicated
      with reasonable certainty a reocclusion or significant restenosis whereas the
      sensitivity of the ABI was poor in detecting significant restenosis after PTA of
      occlusions of the superficial femoral artery. When only clinical criteria were
      used, the true patency rate was significantly overestimated as more than half of
      all reobstructions remained asymptomatic.

PMID- 7819717
TI  - Shock wave treatment of salivary duct stones: substantial progress with a
      minilithotripter.
AB  - Extracorporeal shock wave lithotripsy has recently been introduced as the first
      non-operative treatment alternative for patients with sialolithiasis. Using
      conventional multipurpose lithotripters, however, successful treatment was
      achieved in only 36%-53% of patients. Therefore we developed an miniaturized
      lithotripter meeting the special requirements for extracorporeal shock wave
      treatment in the head and neck region. During a 1-year prospective trial clinical
      efficacy and safety were compared in 40 patients treated with a conventional
      electromagnetic lithotripter (group A) to 33 patients treated with the newly
      developed, miniaturized device (group B). The groups did not differ statistically
      regarding stone size or number or the proportion of stones located in the
      submandibular or parotid gland. Successful stone targeting, a prerequisite for
      shock wave treatment, was achieved by means of in-line ultrasonography in 30 of
      the 40 patients in group A and in 29 of 33 patients of group B. The number of
      shock wave impulses administered per session and the maximum shock wave
      intensities did not differ in the two groups. Significantly more frequent
      treatments with a longer mean duration of each session were required in group A
      (2.4 +/- 1.0 treatments, 47 +/- 11 min) than in group B (1.9 +/- 0.7 treatments,
      28 +/- 9 min; P < 0.05). After a 3 month follow-up significantly more patients
      were free of stones in group B (22/33) than in group A (16/40; P < 0.05).
      Correspondingly, the number of patients free of complaints was significantly
      higher in group B (27/33) than in group A (22/40; P < 0.05).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7819716
TI  - Serum levels of adhesion molecules and thrombomodulin as indicators of vascular
      injury in severe Plasmodium falciparum malaria.
AB  - Severe Plasmodium falciparum malaria is characterized by multiple organ
      involvement due to sequestration of infected erythrocytes in small vessels.
      Endothelial cell adhesion molecules play an important role in this interaction.
      During the course of a severe cerebral P. falciparum malaria infection we found
      very markedly elevated levels of the soluble adhesion molecules intercellular
      adhesion molecule-1, E-selectin, and vascular cell adhesion molecule-1, with a
      maximum increase of nine, seven, and eight times, respectively. These very high
      levels of soluble adhesion molecules point to an endothelial cell injury as an
      additional cause to physiological release or shedding due to receptor
      interactions. Soluble thrombomodulin (sTM) levels showed an extremely marked
      elevation up to 332 ng/ml (up to 13 times the normal value) as well. Malaria
      patients without severe organ involvement/cerebral manifestation showed only a
      mild elevation of sTM levels. TM is a parameter independent of the immunological
      system. It is regarded as a marker of vasculitis and endothelial cell
      destruction. Therefore, markedly elevated sTM levels document a substantial
      endothelial cell injury in severe malarial infection and may be of diagnostic and
      prognostic importance.

PMID- 7819718
TI  - Increasing sensitivity and specificity of Doppler sonographic detection of renal
      transplant rejection with serial investigation technique.
AB  - Acute rejection episodes are the most common cause leading to loss of renal
      grafts in the early postoperative phase. Doppler sonography presents a
      noninvasive tool to detect increased arterial blood flow resistance as a result
      of rejection. This can be measured by the increase in the resistive index (RI)
      and the pulsatility index (PI). In a prospective study including 65 consecutive
      patients we investigated whether the detection of rejection episodes is improved
      by determining RI or PI serially twice a week instead of performing a single
      examination in cases of transplant dysfunction. In 330 examinations with a color
      coded Doppler device (Philips QAD 1, Philips Medical Systems Hamburg, Germany)
      flow profiles were obtained by means of pulse-wave Doppler over at least three
      interlobar arteries of the renal transplant and RI and PI were calculated. In 41
      cases primary rejections were better recognized by an increase in PI compared to
      the preceding value than by the absolute PI value (with a sensitivity of 90%;
      specificity was 76% and 42% respectively). The RI was less specific (with a
      sensitivity of 90%; specificity was 47% for the relative RI increase and 30% for
      the absolute RI value). The continuous PI increase started an average of 3.3 days
      (95% CI-15.25 to + 1.55) before rejection was diagnosed. Vascular rejection
      episodes showed higher PI values than interstitial rejections (3.86 +/- 2.14 vs.
      2.19 +/- 0.87; P < 0.01). The serial investigation technique of PI allows better
      recognition of rejection episodes than the single measurement of RI or PI
      performed so far. Doppler sonography recognizes rejection at an early stage.

PMID- 7819719
TI  - Hepatocellular-cholestatic liver injury due to amoxycillin-clavulanic acid
      combination.
AB  - Two cases (first cases from Poland and Eastern Europe) with liver injury due to
      amoxycillin-clavulanic acid (augmentin) are reported. Pruritus and jaundice were
      the main symptoms. Liver biopsy revealed mixed hepatocellular-cholestatic liver
      injury in both cases. In addition, in one case the microgranulomalike aggregate
      of inflammatory cells was found. Clinical and laboratory abnormalities returned
      to normal within 13 weeks.

PMID- 7819722
TI  - Exercise echocardiography and thallium 201 single-photon emission computed
      tomography in male patients after an episode of unstable coronary artery disease.
AB  - To compare modern, digital exercise echocardiography and thallium 201 single
      photon emission computed tomography (SPECT) in patients with unstable coronary
      artery disease, 65 men unselected with regard to echocardiography were
      prospectively investigated 1 month after an episode of unstable angina or non-Q
      wave myocardial infarction. Exercise echocardiography and 201Tl SPECT were
      performed on consecutive days in connection with a standard symptom-limited
      upright bicycle test and analyzed in a 9-segment model. Coronary angiography was
      performed in all but 1 patient and 60 patients had significant coronary lesions.
      Wall motion abnormalities were seen in 53 patients (81%) at rest and perfusion
      defects in 57 patients (88%) at the redistribution images. New or worsening of
      wall motion abnormalities were seen in 55 patients, either seated at peak
      exercise or recumbent after exercise, and 43 patients had reversible or partially
      reversible 201Tl scintigraphic defects (P = .02). The segmental agreement between
      wall motion abnormalities and scintigraphic defects was low (58%). The additional
      value of exercise echocardiography and 201Tl SPECT to exercise test was greatest
      in patients with one-vessel disease. Thus, 1 month after an episode of unstable
      coronary artery disease in men, there is a high incidence of significant coronary
      stenoses as well as signs of ischemia shown both by wall motion abnormalities
      during exercise echocardiography and by postexercise studies with 201Tl SPECT.
      Exercise echocardiography gives a higher diagnostic yield regarding occurrence of
      reversible ischemia.

PMID- 7819721
TI  - Apolipoprotein E phenotype and lipoprotein(a) in familial hypercholesterolaemia:
      implication for lipoprotein(a) metabolism.
AB  - The mechanisms regulating plasma levels of lipoprotein(a) [Lp(a)] are largely
      unknown. A two- to three-fold increase in Lp(a) levels in patients with familial
      hypercholesterolaemia (FH) has implied that LDL receptor activity may be an
      important factor in determining plasma Lp(a) levels, as it is in determining low
      density lipoprotein (LDL) cholesterol concentration. Common apolipoprotein E
      (apoE) variants also affect plasma LDL cholesterol levels. We therefore examined
      the effect of the common apoE variants on plasma Lp(a) levels in 149 patients
      with heterozygous FH. Patients with the apoE2 allele (n = 11) had significantly
      higher plasma levels of LDL cholesterol compared to those with a apoE3E3
      phenotype, while patients with the apoE4 isoform had similar levels. However,
      there was a significant effect of the apoE2 allele in lowering Lp(a) levels,
      compared to the apoE3E3 group. The median Lp(a) concentration in patients
      possessing an apoE2 isoform was 13.1 mg/dl below the median, while in those with
      an apoE4 allele the median Lp(a) levels were 4.13 mg/dl higher. There was a
      marked inverse correlation between plasma Lp(a) and LDL cholesterol concentration
      in the FH patients carrying the apoE2 allele. Our data imply that difference in
      Lp(a) levels observed between FH patients with different apoE isoforms does not
      result from altered clearance of Lp(a) via the LDL receptor pathway, and suggest
      that apoE mediated hepatic up-take, or conversion, of remnant particles may be
      determining Lp(a) production rate.

PMID- 7819723
TI  - Evaluation of left ventricular hypertrophy by M-mode echocardiography in patients
      and experimental animals.
AB  - In validation studies, M-mode echocardiography has been shown to measure left
      ventricular (LV) mass with reasonable accuracy (r > or = .90 v necropsy
      measurements) in species ranging in body size from humans to rats. The
      sensitivity of antemortem echocardiography for the detection of necropsy LV
      hypertrophy as a qualitative abnormality has also been high (85% to 100%).
      Increased LV mass is strongly related to both increased blood pressure and to
      being overweight or to other causes of increased cardiac volume work. LV mass is
      also increased in the presence of exaggerated blood pressure responses to
      everyday activity, high sodium intake and blood viscosity, and genetic factors
      predisposing to hypertension. Indexation of LV mass by body surface area or
      height has advantages for the detection of hypertrophy related to hypertension or
      obesity. Indexation of LV mass for the power of its relation to height (2.7)
      revealed by analysis of growth (allometric) relations may accomplish both these
      goals. Recent research indicates that the level of LV mass measured by M-mode
      echocardiography is a stronger predictor of subsequent morbid events and death
      than blood pressure or other conventional risk factors except age. Preliminary
      findings of close relations between LV mass and arterial disease and between the
      change in LV mass during antihypertensive treatment and subsequent events
      contribute to explaining the strong predictive value of LV mass.

PMID- 7819724
TI  - Two-dimensional echocardiography for determination of left ventricular mass.
AB  - Two-dimensional (2-D) echocardiography is an effective method for determination
      of left ventricular (LV) mass in patients with normal or abnormal LV geometry.
      Two geometric approaches have been validated and are recommended by the American
      Society of Echocardiography: an area-length approach and a truncated ellipsoid
      geometry. Both rely on short-axis imaging for determining myocardial cross
      sectional area. Whereas M-mode LV mass has been widely used in hypertension,
      where LV geometry is usually normal, 2-D echocardiography LV mass has been
      applied less widely. Recent developments in echocardiography will further enhance
      the utility of these methods, including three-dimensional uses of 2-D
      echocardiographic data, automatic edge detection, and multiplanar transesophageal
      imaging.

PMID- 7819725
TI  - Evaluation of left ventricular hypertrophy by magnetic resonance imaging.
AB  - Left ventricular hypertrophy, manifested as an increase in left ventricular mass,
      is commonly seen as a response to heart disease of various etiologies. Regression
      of hypertrophy may serve as a gauge to the efficacy of treatment. Although many
      methods are available for determination of mass, most of these either visualize
      the heart in limited numbers of planes and therefore require that assumptions
      about left ventricular shape be made, or are dependent on homogeneous myocardial
      perfusion. These assumptions may be invalid in disease status. Magnetic resonance
      imaging allows high-resolution visualization of the entire heart, and therefore,
      accurate measurement of left ventricular mass, in a fashion that does not depend
      on shape or perfusion. This is the method of choice for mass determination in
      clinical investigations and for serial evaluation of selected patients.

PMID- 7819720
TI  - Tumor suppressor genes in molecular medicine.

PMID- 7819726
TI  - Atypical presentation of left main coronary artery disease.

PMID- 7819727
TI  - Ethical dimensions of the care of patients with glaucoma.
AB  - The thesis of this report is that ethical considerations frequently take
      precedence over other considerations in the care of patients with glaucoma. This
      relates at least partially to the still incomplete knowledge regarding the
      diagnosis and management of patients with glaucoma. The surest way to avoid
      damaging patients on the basis of incorrect information is to make certain that
      we recall the fallibility of our knowledge and that we listen to the patient with
      all our attention, so that we can truly hear who he or she is and what it is that
      he or she needs or wants. In so doing not only do we have the best chance to
      respect the patient's autonomy, but to avoid doing harm and to be active in
      helping. These are ethical, not technical considerations.

PMID- 7819728
TI  - Congenital Brown's syndrome: clinical and surgical approach.
AB  - Brown's syndrome is a well-recognized clinical disorder of ocular motility
      consisting mainly of a restriction of active and passive elevation in adduction.
      We report a series of 17 patients with true Brown's syndrome and discuss the
      clinical features and results of surgical intervention. Surgery should be
      considered carefully for the treatment of this syndrome as reoperation may be
      necessary and spontaneous resolution is seen during long-term follow-up of some
      patients.

PMID- 7819729
TI  - The effect of acute ethanol consumption on the human retinal circulation: a study
      in diabetic and non-diabetic subjects.
AB  - The effects of acute ethanol consumption on retinal haemodynamics and retinal
      vascular autoregulation to oxygen in the human retinal circulation were studied
      in 10 diabetic (mean age +/- SD: 38.2 +/- 11.1) and 16 non-diabetic (mean age +/-
      SD: 32.4 +/- 8.8) subjects. Subjects drank 0.5 g of ethanol, as vodka, per kg of
      body weight, diluted in sugar-free orange juice. Retinal blood flow was
      determined using laser Doppler velocimetry and computerised image analysis. The
      effect of ethanol on oxygen reactivity, as a measure of autoregulation, was also
      determined after 60% oxygen inhalation. All subjects demonstrated a significant
      fall in mean arterial blood pressure (control group 3.3%, p = 0.04, diabetic
      subjects 5.7%, p = 0.05), after ethanol intake. Ethanol caused no significant
      change in retinal blood flow. Oxygen reactivity was found to be 38.3% (22.4-47.7,
      median and interquartile range) in the non-diabetic subjects at baseline, and
      30.7% (10.8-42.1) after ethanol ingestion. In diabetic subjects, the oxygen
      reactivity was 33.2% (19.8-46.8) at baseline and 24.5% (21.1-32.1) after ethanol.
      In this study ethanol did not significantly affect retinal blood flow or impair
      autoregulation. These results suggest that the retinal circulation may be able to
      autoregulate despite the presence of ethanol, in contrast to other vascular beds
      where ethanol changes flow.

PMID- 7819730
TI  - Risk factors for intraoperative and early postoperative complications in
      extracapsular cataract surgery.
AB  - The risk factors for intraoperative and early postoperative complications were
      evaluated in 351 consecutive cataract operations at the Oulu University Hospital
      in 1990. Bleeding into the anterior chamber during the operation was recorded in
      8.6%, zonular rupture in 6.6%, posterior capsular rupture in 5.4% and vitreous
      loss in 3.2%, On account of the loss of capsular support an anterior chamber
      intraocular lens was implanted in 3.1%. Of the early postoperative complications,
      signs of fibrinous reaction were observed in 24.5%, corneal edema in 53.6% and
      rise of intraocular pressure to 30 mmHg or more in 27.6%. There was no difference
      in the complication rate between men and women or in relation to age. The use of
      anticoagulant (although discontinued before surgery) or antiplatelet medication
      increased the risk of intraoperative bleeding but no sight-threatening bleeding
      occurred. The use of acetylsalicylic acid was also associated with an increased
      risk of postoperative fibrinous reaction. Other systemic diseases like systemic
      hypertension, diabetes, asthma, or cardiac or mental disorders, or medications,
      did not increase the complication rate. Of the various ocular parameters, small
      pupil and exfoliation syndrome were the most important risk factors for both
      intra- and early postoperative complications, and the presence of glaucoma
      increased the risk of vitreous loss, postoperative pressure rise and corneal
      edema. General anesthesia did not seem to reduce the complications rate.

PMID- 7819731
TI  - Serotonin in human tears.
AB  - It has been postulated that serotonergic receptors are present in the corneal
      epithelium and that their activation by serotonin released from subepithelial
      corneal nerves raises the level of cyclic AMP, which in turn stimulates active CI
      secretion by the corneal epithelium. We looked for serotonin in tears because
      these bathe the corneal epithelium. Twenty-two normal subjects, 14 women and 8
      men between 25 and 60 years of age (average 36.5 +/- 9 years), participated in
      this study. Twenty microliters of tears were collected in capillary tubes after
      trigeminal stimulation (pepper in the nose) and were immediately analysed using
      high-performance liquid chromatography with electrochemical detection. Serotonin
      was identified and measured in every subject. Its mean concentration was 2.74 +/-
      1.99 ng/ml. No difference was found between women and men. Emotionally evoked
      tears were obtained from two subjects. The amount of serotonin in these samples
      was much higher than in the samples obtained by trigeminal stimulation. These
      results demonstrate for the first time that serotonin is present in human tears.
      The possible role of this serotonin in chloride transport in the corneal
      epithelium and the probable difference between "emotional" and stimulated tears
      warrants further investigation.

PMID- 7819732
TI  - Macular grid photocoagulation in persistent macular edema due to central retinal
      vein occlusion.
AB  - AIM: Macular edema is still the main cause of poor visual prognosis in central
      retinal vein occlusion (CRVO). This study was designed to establish whether grid
      photocoagulation is effective in the management of this disorder. METHODS: The
      records of 16 patients who had undergone macular grid photocoagulation for
      persistent macular edema due to CRVO were reviewed retrospectively. Pre-treatment
      visual acuity ranged from 20/400 to 20/40, and laser treatment was done six
      months or more after the onset of the disease. RESULTS: Biomicroscopy and
      fluorescein angiography showed the improvement or disappearance of macular edema
      in 14/16 patients (87.5%). Improved visual acuity was observed in eight (50%) and
      no improvement or reduced vision in the other eight (50%). A poorer prognosis was
      statistically correlated with older age (p < 0.03), macular ischemia (p < 0.001),
      foveal avascular zone larger than 1/2 disc diameter (p < 0.05) and pigmentary
      clumps in the foveal area (p < 0.05). Laser treatment was ineffective for most
      patients with systemic vascular risk factors and pre-treatment visual acuity
      below 20/200. CONCLUSION: Macular grid photocoagulation may be effective for
      drying up, or at least reducing, macular edema due to CRVO and some improvement
      of vision can be expected in half the cases.

PMID- 7819733
TI  - Efficacy of collagen shields after extracapsular cataract extraction.
AB  - The efficacy of presoaked porcine collagen shields was compared with
      subconjunctivally injected corticosteroids and antibiotics in reducing ocular
      inflammation after ECCE with IOL implantation, and signs of reduced oxygen
      delivery to the cornea were assessed. Fifty eyes of fifty patients were
      recruited. At the end of surgery 25 eyes (group 1) received a 24-h shield
      presoaked with 0.1% betamethasone disodium phosphate and 0.5% netilmycin. The
      other 25 eyes (group 2) received 1 mg betamethasone disodium phosphate and 250 mg
      piperacillin as a subconjunctival injection. The eyes were then taped closed.
      Inflammatory parameters (anterior chamber flare, fibrin, folds of Descemet's
      membrane, corneal edema) and tolerability of the delivery system (pain, itching)
      were evaluated 24 h after surgery. None of the patients lost the shield and the
      collagen devices were well tolerated. Groups 1 and 2 showed no significant
      differences in the parameters considered. There was, however, transient, slight
      diffuse superficial corneal edema in 24% of group 1 and 4% of group 2, raising
      the question of inadequate oxygen transmission through collagen shields under
      closed lids. The results suggest that collagen shields used with the right
      solution have no significant adverse effect and may be a less invasive
      alternative to subconjunctival injection.

PMID- 7819734
TI  - Lens coloboma and Alport-like glomerulonephritis.
AB  - An unusual case of bilateral lens coloboma and Alport-like glomerulonephritis is
      reported. In a 12-year-old boy and in several family members; Alport-like
      glomerulonephritis was diagnosed without deafness and without ocular signs of
      Alport syndrome. A bilateral lens coloboma however was observed in the
      propositus. To our knowledge this is the first reported case of lens coloboma
      with Alport-like glomerulonephritis.

PMID- 7819735
TI  - p53 protein overexpression in a case of conjunctival micro-invasive carcinoma.
AB  - We analysed by immunohistochemistry the expression of p53 protein in a case of
      micro-invasive carcinoma of the conjunctiva. About 50% of tumor cells showed a
      strong nuclear positivity for p53. This suggests that p53 gene alterations play a
      role in the development of this type of tumor.

PMID- 7819736
TI  - Selective induction of interleukin-4- and interferon-y-producing T cells from
      cord blood naive T cells. Effects of costimulatory signaling through CD28.
AB  - We investigated the effect of costimulation through CD28 and CD11a on the
      differentiation of human naive CD4+ T cells with restricted cytokine production
      profiles. Interleukin (IL)-4 and interferon-gamma (IFN-gamma) were measured by
      ELISA and IL-2 was detected by a bioassay. Naive CD4+ T cells proliferated and
      produced IL-2 upon cross-linking of CD3, and costimulation through CD28 enhanced
      IL-2 production. After repeated stimulation, CD4+ T cells which were stimulated
      in the absence of costimulation through CD28 lost their ability to secrete IL-2
      and started secreting IL-4 and IFN-gamma. Instead in the presence of
      costimulation through CD28, they secreted IL-2, IL-4 and IFN-gamma. Blocking of
      endogenous IL-4 activity with anti-IL-4 Ab suppressed the IL-4 secretion and
      proliferation of T cells.

PMID- 7819737
TI  - Inhibition of cell growth by macrophage membrane lipid molecule.
AB  - Macrophage hybridoma clone 5 suppressed B-cell proliferation induced by
      lipopolysaccharide (LPS). Since paraformaldehyde-fixed macrophages exerted the
      effect, macrophage-derived mediators were excluded from the inhibition. The
      inhibitory property of macrophages was present in the membrane fraction and was
      recovered in the organic phase after extraction using a chloroform/methanol/water
      system followed by hexane extraction. Therefore, the inhibitory activity found in
      macrophage clone 5 was concluded to arise from a lipid component. The inhibitory
      substance was further purified to a homogeneity by LH20 column fractionation
      using methanol/chloroform as the mobile phase. The purified lipid did not have
      any effect on the LPS-mediated induction of MHC class II molecules on the B-cell
      surface. Moreover, the inhibitory property was shown to affect growth of a wide
      variety of tumor cell lines of human origin. These results suggest that a lipid
      molecule found on the cell membrane of cloned macrophage hybridoma may
      participate in the regulation of cell growth through cell contact.

PMID- 7819738
TI  - Localization of intracellular monoclonal antibody specific for mycobacteria in
      experimentally induced pulmonary tuberculous lesion.
AB  - To determine the intracellular localization of intravenously injected infection
      specific monoclonal antibodies (mAbs) in the infected cells, immunohistochemical
      staining was carried out in an animal model having pulmonary tuberculous lesions
      induced by inoculation of heat-killed Mycobacterium tuberculosis H37Rv. One
      milligram of intact mouse mAb against mycobacteria (group I, n = 10) and F(ab')2
      (group II, n = 6) was intravenously injected to the rabbits of each group.
      Immunohistochemical staining using an antimouse Ab was performed at days 1, 3, 5,
      7 and 8 in group I and at days 1, 2 and 3 in group II by the streptavidin-biotin
      method. For the control study, 1 ml of nonspecific polyclonal human IgG (group
      III, n = 10) and 100 micrograms of normal rabbit IgG F(ab')2 (group IV, n = 6)
      was injected to rabbits and guinea pigs having tuberculous inflammation,
      respectively. Both groups (group I and II) showed a positive antigen (Ag)-Ab
      reaction within the cytoplasm of monocytes. A weak but positive reaction was
      observed intracellularly in group III; however, no positive reaction was seen in
      group IV. Our results suggest that an intracellular Ag-Ab reaction plays an
      important role in the localization of infection by immunoscintigraphy using
      specific mAb fragments.

PMID- 7819739
TI  - Nitrocellulose-RAST analysis of allergenic cross-reactivity of Candida albicans
      and Saccharomyces cerevisiae mannans.
AB  - Two chemically purified mannan preparations and one affinity purified mannan
      preparation of Candida albicans and Saccharomyces cerevisiae were analyzed for
      allergenic cross-reactivity. Simultaneous IgE binding in radioallergosorbent test
      (RAST) was studied with all preparations and the chemically purified mannans were
      also used for RAST inhibitions. The yeast mannans were purified with the Peat
      method, using repeated ethanol precipitations and Fehling's precipitation in
      alkaline conditions, and the Cetavlon method, using hexadecyltrimethylammonium
      bromide and ethanol precipitations. Affinity purification of the mannans was
      performed with concanavalin A lectin bound to a Sepharose column. Mannan from
      Pityrosporum ovale was purified with the Cetavlon method for analysis of
      simultaneous RAST reactivity. Simultaneous IgE binding to all the studied yeast
      mannans was generally seen in all the studied sera of patients suffering from
      atopic dermatitis. The strongest responses were seen against C. albicans mannan,
      especially the Cetavlon mannan. In the RAST inhibition studies IgE binding to S.
      cerevisiae mannan was completely inhibited by C. albicans mannan preparations,
      whereas reciprocal inhibition was not complete. These results indicate that in
      atopic dermatitis simultaneous IgE response to yeast polysaccharides occurs and
      that the major sensitizer is C. albicans and IgE antibodies against S. cerevisiae
      mannan are cross-reacting.

PMID- 7819740
TI  - Responsiveness of peripheral blood mononuclear cells from normal and atopic
      donors to microbial superantigens.
AB  - Patients with atopic dermatitis (AD) are frequently colonized with Staphylococcus
      aureus strains secreting exotoxins such as the staphylococcal enterotoxin B (SEB)
      and A (SEA). Nonetheless the role of SEB and SEA in AD is yet unknown. We
      analyzed the responsiveness of peripheral blood mononuclear cells (PBMCs) and
      isolated T cells from donors with AD and from normal donors to SEB and SEA. PBMCs
      as well as T cells from normal donors showed a significantly enhanced
      proliferation after stimulation with enterotoxin B, whereas the 3H-thymidine
      uptake of the T lymphocytes from patients with AD was markedly suppressed.
      Furthermore, we show that IFN-gamma mRNA and protein and mRNA for both chains of
      IL-12 (p35 and p40) are produced in human PBMCs from normal donors upon
      stimulation with SEB and SEA. In contrast to normal donors T cells from donors
      with AD predominantly express mRNA for IL-4, IL-5, and only diminished levels for
      IFN-gamma and IL-12 upon stimulation with SEB and SEA. Furthermore, in contrast
      to normal donors, PBMCs from donors with AD spontaneously produce high levels of
      IgE and express increased levels of CD23, the low-affinity receptor for IgE.
      Nonetheless, the superantigens by themselves, from 0.1 fg up to 1 microgram/10(6)
      cells, induced neither IgE secretion nor CD23 expression on PBMCs. Moreover, the
      addition of superantigens to IL-4-treated PBMC cultures diminished or totally
      suppressed the IL-4-induced IgE synthesis and CD23 expression. No differences
      were observed between PBMCs from normal donors of donors with AD. Both PBMCs
      isolated from normal and atopic donors produced high levels of soluble IL-4
      receptor (up to 210 +/- 90 pg/ml). Addition of soluble IL-4-receptor to PBMC
      cultures downregulated the IL-4-induced IgE synthesis and CD23 expression in
      unstimulated as well as in SEB-stimulated PBMCs from normal donors and donors
      with AD. Our results suggest that superantigen-producing staphylococcal strains
      on the skin of patients with AD may modulate and/or amplify allergic
      inflammation.

PMID- 7819741
TI  - Antibody response against wheat, rye, barley, oats and corn: comparison between
      gluten-sensitive patients and monoclonal antigliadin antibodies.
AB  - The antibody response of patients with gluten-sensitive enteropathy and
      dermatitis herpetiformis against alcohol-soluble prolamines of wheat, rye,
      barley, oats and corn assessed by immunoblotting was compared to the staining
      patterns produced by monoclonal antigliadin antibodies. Both monoclonal
      antibodies (MAbs) and patient serum reacted with wheat, rye, barley and oats, the
      patient serum showing individual variation both in IgA and IgG stainings. A broad
      reactivity with polypeptides from 30 to 68 kD was, however, typical for patient
      serum and comparable to the reactivity of two broadly reacting antigliadin MAbs.
      This kind of broad reactivity of the MAb may suggest that it binds to glutamine
      repeating sequences of highly homologous gliadin polypeptides. Glutamine- and
      proline-containing motifs Pro-Ser-Gln-Gln and Gln-Gln-Gln-Pro are also included
      in the peptides toxic to the celiac small intestinal mucosa. Our study indicates
      that the humoral response of the patients may detect similar structures, in oat
      prolamines as well. Patient serum and one of the MAbs also reacted with a 22-kD
      polypeptide of corn extract. The meaning of this reactivity is not known, and
      further characterization of the antigenic epitopes of different cereals will be
      important.

PMID- 7819742
TI  - Interleukin-5 upregulates intercellular adhesion molecule-1 gene expression in
      the nasal mucosa in nasal allergy but not in nonallergic rhinitis.
AB  - The effect of interleukin-5 (IL-5) on intercellular adhesion molecule-1 (ICAM-1)
      gene expression in human nasal mucosa was studied using the method of gene
      expression quantification. Recombinant human IL-5 was shown to induce ICAM-1 gene
      expression in the nasal mucosa of patients with nasal allergy, but not in the
      mucosa of non-allergic patients. The peak level of ICAM-1 gene expression was
      seen 6 h after IL-5 stimulation. In the nasal mucosa of patients with nasal
      allergy, IL-5 might act not only as an eosinophil chemotactic factor, but also as
      an enhancement factor for the expression of adhesion molecules, thereby
      accelerating eosinophil appearance. The results also suggest that the nasal
      mucosa of patients with nasal allergy somehow favors adhesion molecule induction
      by IL-5.

PMID- 7819743
TI  - Prevalence of atopy and pollinosis in the adult population of Switzerland
      (SAPALDIA study). Swiss Study on Air Pollution and Lung Diseases in Adults.
AB  - The Swiss SAPALDIA study is a large multicenter cross-sectional study initiated
      in 1991 to evaluate the relationship between environment and respiratory symptoms
      and diseases in adults, and included subjects from eight areas in Switzerland
      with distinctive environmental characteristics. We present here prevalence data
      for atopy, pollinosis and atopic asthma obtained from a random sample of 8,357
      adults (18-60 years) assessed by standardized computer-based interview as well as
      by allergy skin prick tests (SPTs) (performed with Phazet) to grass, birch and
      Parietaria pollen, house dust mite, cat and dog epithelia and the moulds
      Alternaria and Cladosporium and by an in vitro allergy screen test (Phadiatop CAP
      FEIA system). On the basis of a positive Phadiatop (total 28.9%; males 32.9%,
      females 25.0%; p < 0.001) and/or a positive SPT (total 23%; males 25.0%, females
      20.8%; p < 0.001), 32.3% of the study population were considered atopic (males
      35.7%, females 28.8%; p < 0.001). Concerning the prevalence of skin sensitization
      (SPT wheal > or = 3 mm), the highest rate was observed for grass (12.7%),
      followed by house dust mite (8.9%), silver birch (7.9%), cat (3.8%) and dog
      (2.8%), whereas moulds and Parietaria elicited less than 1% positive SPTs. The
      prevalence of atopic rhinitis (rhinitis symptoms associated with atopy) was 13.5%
      (males 14.3%, females 12.6%; p < 0.05) and the prevalence of current hay fever
      varied between 9.1% (questionnaire answer and a positive SPT to at least one
      pollen), 11.2% (questionnaire answer and presence of atopy) to 14.2%
      (questionnaire answer only) with no significant difference by sex.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7819744
TI  - Effects of oxatomide and KW-4679 on acetylcholine-induced responses in the
      isolated acini of guinea pig nasal glands.
AB  - The antiallergic drugs oxatomide and KW-4679 were assessed to show inhibitory
      effects on ionic currents and intracellular Ca2+ concentration ([Ca2+]i) increase
      induced by acetylcholine (ACh) in isolated acini of the guinea pig nasal gland.
      Both K+ and Cl- currents evoked by ACh were inhibited by addition of oxatomide
      and KW-4679 at the concentration of 10(-5) M. KW-4679 (10(-5) M) inhibited the
      increase in [Ca2+]i induced by ACh, whereas no effect of oxatomide (10(-5) M) on
      Ca2+ responses was observed. These findings suggest that both drugs suppress
      electrolyte and fluid secretion in the nasal glands by different mechanisms.

PMID- 7819745
TI  - IFN-gamma-stimulated human vascular endothelial cells function as accessory cells
      for superantigen-induced TNF production in human T cells.
AB  - In the presence of IFN-gamma-stimulated vascular endothelial cells which have
      acquired HLA class II molecules, T cells produced tumor necrosis factors (TNF
      alpha and TNF-beta) and IL-2 in response to stimulation with streptococcal
      pyrogenic exotoxin A.

PMID- 7819746
TI  - Murine recombinant interleukin-12 increases the acquisition of allergic contact
      dermatitis in the mouse.
AB  - Interleukin-12 (IL-12) is a heterodimeric cytokine that has pleiotropic effects
      on the immune response. We have studied the effect of recombinant IL-12 on
      allergic contact dermatitis in the mouse. IL-12 substantially up-regulates the
      induction of sensitivity to the contact allergens dinitrofluorobenzene and
      oxazolone.

PMID- 7819747
TI  - Induction of insulin antibodies and insulin allergy under alpha-interferon
      treatment of renal cell carcinoma in a patient with insulin-treated diabetes
      mellitus--a case report.
AB  - The induction of insulin antibodies and the development of an insulin allergy
      were observed in a male diabetic patient treated with insulin during alpha-IFN
      therapy of renal cell carcinoma. Diabetes and renal cell carcinoma were diagnosed
      at the same time. The patient was treated with biosynthetic human insulin and
      nephrectomy was performed. Four months later, antineoplastic chemotherapy was
      started (alpha-IFN, vinblastin). Six weeks after initiation of alpha-IFN
      injections, the patient reported signs of insulin allergy. Significant titers of
      insulin antibodies of both the IgG and IgE subclasses were found in the serum at
      that time and during follow-up, but not before the treatment with alpha-IFN. None
      of the other autoantibodies investigated were positive.

PMID- 7819748
TI  - Idiopathic eosinophilic pneumonia and pregnancy: report of a case.
AB  - A case of chronic eosinophilic pneumonia and pregnancy is reported. In 1989, a 24
      year-old woman with chronic eosinophilic pneumonia became pregnant. We decided
      not to stop steroid therapy. Except for premature preterm rupture of the membrane
      she had a uneventful pregnancy and a male infant with no distress syndrome.

PMID- 7819749
TI  - Cytokines and sleep.
AB  - Infectious challenges induce sleep responses in the host characterized by an
      increase in non-rapid eye movement sleep (NREMS) followed by a period of
      decreased NREMS. Such sleep responses represent one facet of the acute phase
      response and are thus probably beneficial to the host. Certain bacterial cell
      wall products such as lipopolysaccharide and peptidoglycan and viral double
      stranded RNA also induce sleep responses. These microbial products share the
      ability to enhance cytokine production. Some cytokines such as interleukin-1,
      tumor necrosis factor, interferon-alpha and acidic fibroblast growth factor are
      somnogenic. Cytokines in turn alter production of neuroendocrines and
      neurotransmitters, e.g., growth hormone releasing hormone and nitric oxide, which
      are known to be involved in sleep-wake regulation. Microbial-altered sleep thus
      likely involves an amplification of ongoing normal sleep regulatory mechanisms.

PMID- 7819750
TI  - Determination of chlorobiphenyls in cleaned-up seal blubber and marine sediment
      extracts: interlaboratory study.
AB  - An interlaboratory study on the determination of individual chlorobiphenyl
      congeners (CBs) in cleaned-up seal blubber and marine sediment extracts was
      organized by the International Council for Exploration of the Sea, the
      Intergovernmental Oceanographic Commission, and the Oslo and Paris Commissions,
      as the second part of a step-wise-designed interlaboratory study on the
      determination of CBs in marine media. Fifty-eight laboratories from 16 countries
      participated in this exercise, which involved the determination of 10 CBs in a
      standard solution, a cleaned-up seal blubber extract, and a cleaned-up marine
      sediment extract. Suggestions were given for instrument optimization. Standard
      errors of 1.16-1.17 for the standard solution, 1.20-1.33 for the seal blubber
      extract, and 1.31-1.56 for the sediment extract were obtained for CBs 52, 101,
      118, 138, 153, and 180 by all laboratories with the exception of the laboratories
      giving consistently outlying results. The results for CBs 28, 31, 105, and 156
      showed larger standard deviations. The 2 major difficulties for participants in
      this exercise were correct preparation of a calibration solution and
      chromatographic separation. The results of the sediment analysis showed a
      complete lack of agreement. It is recommended that, prior to the organization of
      the third part of this study, participants should install gas chromatographic
      columns with minimum lengths of 50 m and maximum internal diameters of 0.25 mm
      and should prepare calibration solutions from solids of known purity.

PMID- 7819751
TI  - Radionuclides in domestic and imported foods in the United States, 1987-1992.
AB  - Findings from the U.S. Food and Drug Administration's Radionuclides in Foods
      program are summarized for foods collected between October 1, 1986, and September
      30, 1992. Concentrations of radionuclide activity in the Total Diet Study and
      reactor-survey foods were in Range 1 or low in Range II of the surveillance and
      control recommendations of the Federal Radiation Council; no control actions were
      suggested. Dietary intake of 90Sr continued the general decline observed since
      1961. Approximately 2600 test portions of imported foods were analyzed for
      contamination associated with the Chernobyl nuclear accident. Concentrations of
      radionuclide activity were below limits of detection for the vast majority of the
      imported food test portions but were above the levels of concern for 23 portions.
      Since 1986, the fraction of imported food test portions having measurable amounts
      of contamination has steadily declined, as have the average concentrations of
      radionuclide activity; however, contamination is still occasionally found.
      Continued monitoring of both domestic and imported foods is planned.

PMID- 7819752
TI  - Rapid analysis of animal drug residues by microcolumn solid-phase extraction and
      thermal desorption-ion trap mass spectrometry.
AB  - A new approach was developed for the rapid and quantitative determination of an
      anthelmintic drug, phenothiazine, in milk. The technique involves a simple
      extraction procedure using a C18 microcolumn disc, followed by thermal desorption
      of the analyte from the disc directly into an ion trap mass spectrometer. The
      compounds are selectively ionized by isobutane chemical ionization and detected
      by tandem mass spectrometry. With this approach, 10 ppb detection limits were
      achieved with as little as 100 microL milk and only 10 min of analysis time. This
      approach was used to analyze samples of milk taken from a cow administered a one
      time therapeutic dose of phenothiazine. The target compound could be detected at
      56 h post-dosage, corresponding to a concentration of 30 ppb.

PMID- 7819753
TI  - Determination of leucogentian violet in chicken fat by liquid chromatography with
      electrochemical and ultraviolet detection: interlaboratory study.
AB  - A laboratory trial was completed for a liquid chromatographic method that can
      quantitate leucogentian violet (LGV) in chicken fat at 10 ppb. With this method,
      LGV is isolated from the fat matrix by a series of liquid-liquid extractions.
      This trial evaluated 2 detection systems: electrochemical (EC) and ultraviolet
      (UV). The participating laboratories determined incurred residues at 2 levels as
      well as fat samples fortified at 5, 10, and 20 ppb. Using UV detection, the 3
      laboratories reported the following range of recoveries: 71.0-89.6% at 5 ppb,
      74.7-83.9% at 10 ppb, and 77.2-79.0% at 20 ppb. When these same samples were
      chromatographed with EC detection, the 2 reporting laboratories obtained the
      following average recoveries: 79.0 and 92.5% at 5 ppb, 75.9 and 85.4% at 10 ppb,
      and 77.3 and 79.8% at 20 ppb. The average concentrations found for the first
      level of incurred sample were 6.3, 6.3, and 5.4 ppb with coefficients of
      variation (CVs) of 2.4, 7.6, and 33.7%, respectively, when UV detection was used.
      Samples chromatographed with EC detection averaged 6.3 and 6.4 ppb with CVs of
      4.0 and 8.2%, respectively. The second level of incurred sample gave average
      concentrations of 27.6, 29.0, and 10.9 ppb with CVs of 11.0, 5.0, and 42.8%,
      respectively, when the UV detection system was used. With the EC detector, the
      concentrations averaged 27.2 and 30.7 ppb with CVs of 15.7 and 3.5%,
      respectively.

PMID- 7819754
TI  - Extraction and liquid chromatographic analysis of sulfadimethoxine and 4-N
      acetylsulfadimethoxine residues in channel catfish (Ictalurus punctatus) muscle
      and plasma.
AB  - A simple and rapid method was developed for the simultaneous extraction and
      liquid chromatographic (LC) determination of sulfadimethoxine (SDM) and 4-N
      acetylsulfadimethoxine (N-acetyl SDM) in channel catfish muscle and plasma.
      Tissues fortified at 0, 50, 100, 200, 400, and 1000 ppb were examined. Matrix
      solid phase dispersion (MSPD) was used for muscle extraction. Plasma was
      extracted with a modified MSPD procedure in which 100 microL plasma and 400 mg
      C18 were blended by Vortex mixing in a disposable chromatographic column.
      Recovery of SDM based on radioactivity was 79% for muscle and 67% for plasma.
      Standard curves based on extracted fortified samples were used for quantitation
      of N-acetyl SDM. LC run times of 12 min were obtained using a microbore
      analytical column and an isocratic mobile phase of aqueous 0.017M phosphoric acid
      acetonitrile at ratios of 71:29 for muscle and 73:27 for plasma extracts. Method
      detection limits were 26 ng SDM and 26 ng N-acetyl SDM/g muscle, and 33 ng SDM
      and 11 ng N-acetyl SDM/mL plasma. Intra-assay variation was < 10% for both
      compounds at all concentrations examined. Inter-assay variation for SDM was 13%
      for muscle and 14% for plasma, and for N-acetyl SDM was 11% for muscle and 10%
      for plasma.

PMID- 7819755
TI  - Determination of musk ambrette in fragrance products by capillary gas
      chromatography with electron capture detection: interlaboratory study.
AB  - A gas chromatographic method that uses an internal standard additions techniques
      is described for the determination of musck ambrette (MA) in fragrance products.
      A solution containing the product and a known amount of an internal standard,
      musk tibetene (MT), is injected directly into a gas chromatograph equipped with
      an electron capture detector. The chromatographic separation of the components on
      a wide-bore fused silica capillary column is recorded and a response constant is
      calculated from MA and MT peak heights. A similar response constant is also
      calculated for a standard solution containing known concentrations of MA and MT.
      The MA content of the fragrance product is then calculated. Average recoveries of
      MA from fragrance products ranged from 97.6 to 102.3%. The method was also
      evaluated collaboratively by 6 laboratories. In this study, the reproducibility
      relative standard deviation for MA in 6 fragrance test samples ranged from 2.78
      to 22.87%.

PMID- 7819756
TI  - Enzyme-linked immunoassay for detection of Listeria monocytogenes in dairy
      products, seafoods, and meats: collaborative study.
AB  - A collaborative study was conducted to evaluate Listeria-Tek, an enzyme-linked
      immunosorbent assay (ELISA) for detection of Listeria monocytogenes and other
      Listeria spp. in foods. The present ELISA method was compared to the U.S. Food
      and Drug Administration culture method for detection of L. monocytogenes in dairy
      products and seafoods and to the U.S. Department of Agriculture Food Safety and
      Inspection Service method for detection of L. monocytogenes in meats. Replicate
      samples of 6 food types (frankfurters, roast beef, Brie cheese, 2% milk, raw
      shrimp, and crab meat) inoculated with L. monocytogenes and uninoculated control
      samples were analyzed by the collaborators. L. monocytogenes was identified in
      593 samples by the ELISA method and in 574 samples using culture procedures.
      Identical results were obtained for 506 positive samples and 419 negative samples
      using the ELISA and culture methods for an overall agreement rate of 85.6%. The
      enzyme-linked immunoassay for detection of L. monocytogenes in dairy, seafood,
      and meat products has been adopted first action by AOAC INTERNATIONAL.

PMID- 7819757
TI  - Detection of Salmonella in dry foods using refrigerated pre-enrichment and
      enrichment broth cultures: summary of collaborative study.
AB  - A collaborative study was conducted to compare the productivity of refrigerated
      pre-enrichment and enrichment broth cultures with the U.S. Food and Drug
      Administration culture methods for detection of Salmonella. The refrigerated pre
      enrichment and selective enrichment broth culture methods for detection of
      Salmonella in dry foods have been adopted first action by AOAC INTERNATIONAL.

PMID- 7819758
TI  - Identification of Vibrio vulnificus by cellular fatty acid composition using the
      Hewlett-Packard 5898A Microbial Identification System: collaborative study.
AB  - A gas chromatographic method using a capillary column for rapid identification of
      Vibrio vulnificus was examined in a collaborative study. Identifications were
      performed by analysis of cellular fatty acid profiles which were automatically
      searched against reference profiles stored in a computer-generated library. Each
      of the 13 collaborators was sent 15 unknown isolates, which included 10 V.
      vulnificus isolates and 5 negative control isolates. Each collaborator was
      furnished with a computer-generated library, developed by the Dallas U.S. Food
      and Drug Administration laboratory, which contained entries for V. vulnificus, V.
      cholerae, V. fluvialis, V. parahaemolyticus, V. mimicus, and Aeromonas
      hydrophila. Of the 195 isolates sent to the collaborators, results for 190
      isolates were received. The other 5 isolates were nonviable before analyses
      began. Of the 126 V. vulnificus isolates analyzed, 118 (93.7%) were correctly
      identified. Of the 65 negative control isolates sent, one was nonviable, one was
      misidentified as V. vulnificus, and 2 were misidentified as V. parahaemolyticus.
      Of the 64 negative controls analyzed, 95.3% were correctly identified.
      Statistical analysis shows a sensitivity rate of 0.872, specificity rate of
      0.982, false positive rate of 0.010, and false negative rate of 0.206. The gas
      chromatographic method for identification of Vibrio vulnificus by microbial fatty
      acid profile has been adopted first action by AOAC INTERNATIONAL.

PMID- 7819759
TI  - Enzyme-linked immunosorbent assay for detection of zearalenone in corn, wheat,
      and pig feed: collaborative study.
AB  - A direct competitive enzyme-linked immunosorbent assay (ELISA) screening method
      for zearalenone in corn, wheat, and feed at 500 ng/g was evaluated by 23
      collaborators (22 laboratories) in an international collaborative study. Eighteen
      samples of spiked or naturally contaminated corn, wheat, and pig feed were
      prepared by the sponsoring laboratory and sent for testing with complete test
      kits to participating collaborators in Canada, Italy, Sweden, The Netherlands,
      and the United States. Test samples were extracted with methanol-water solution
      (70 + 30) by shaking on a wrist-action shaker for 3 min. A portion of the extract
      was mixed with an equal volume of zearalenone-enzyme conjugate, and the mixture
      was incubated with zearalenone-specific monoclonal antibodies coated onto
      microtiter wells. All test samples were assayed in duplicate. One of 52 (2%)
      blanks was reported positive. Thirty-nine of the 52 (75%) samples that were
      spiked at 500 ng/g were reported as positive. Forty-nine of the 51 (96%) samples
      with concentrations at or above 1000 ng/g were reported as positive. The overall
      incidence of false negatives was 6.0% and the incidence of false positives was
      22.7% by the ELISA method. Only one (3.4%) false negative was reported for
      samples containing > or = 800 ng/g. In the spectrophotometric method, 8
      collaborators determined approximate levels of zearalenone in test samples from
      standard curves constructed from spiked extracts (0-3000 ng/g of each commodity
      tested). This method gave and overall incidence of false negatives of 5.7% and
      false positives of 17.8%. Average relative standard deviations, RSDr
      (repeatability) and RSDR (reproducibility), were 11.6 and 25.1% for spiked
      samples and 11.7 and 33.1% for naturally contaminated samples, respectively.
      Standard curves were constructed with each set of samples assayed. Comparison of
      absorbance values from these standard curves indicate the performance of reagents
      and antibody used in the assay. The ELISA method has been adopted first action by
      AOAC INTERNATIONAL as a screening method for zearalenone at > or = 800 ng/g in
      corn, wheat, and pig feed.

PMID- 7819760
TI  - Extraction of aflatoxins from naturally contaminated peanuts with different
      solvents and solvent/peanut ratios.
AB  - A study was conducted to compare the extraction efficiencies of aflatoxins (B1,
      B2, G1, and G2) from low, medium, and high concentrations (approximately 10, 100,
      and 1000 ppb, respectively) of naturally contaminated peanut samples by using
      different solvents and solvent-to-peanut sample ratios. Solvents used were 80:20
      methanol/water at 2:1, 3:1, and 5:1 solvent to sample ratios; 60:40
      methanol/water at 5:1 solvent to sample ratio; and 90:10 acetonitrile/water at
      2:1 and 4:1 solvent to sample ratios. The solvents 80:20 methanol/water at a 3:1
      ratio of solvent to sample and 90:10 acetonitrile/water at a 2:1 ratio were
      consistently more efficient than all other solvents, regardless of the aflatoxin
      concentration. The solvent 90:10 acetonitrile/water at a 4:1 solvent-to-sample
      ratio was consistently the least efficient regardless of aflatoxin concentration
      based on analytical results with liquid chromatography (LC). The results are
      relevant in selecting an appropriate extraction solvent for use at peanut grading
      points.

PMID- 7819761
TI  - Multifunctional column coupled with liquid chromatography for determination of
      aflatoxins B1, B2, G1, and G2 in corn, almonds, brazil nuts, peanuts, and
      pistachio nuts: collaborative study.
AB  - An AOAC/IUPAC collaborative study was conducted to evaluate the effectiveness of
      a multifunctional column for the determination of aflatoxins. The test portion is
      extracted with acetonitrile-water (9 + 1), the extract is filtered, and the
      filtrate is passed through the column. The aflatoxins in the eluate are
      determined by reversed-phase liquid chromatography after derivatization with
      trifluoroacetic acid. Naturally contaminated corn, almonds, Brazil nuts, peanuts,
      and pistachio nuts spiked with total aflatoxins at 5, 10, 20, and 30 ng/g were
      sent to 12 collaborators in the United States, Denmark, France, Japan, and
      Switzerland. Eleven collaborators completed the study. Average recoveries of
      total aflatoxins for each spike level for the various commodities (excluding
      Brazil nuts at 5 ng/g) were 93, 97, 95, and 95%, respectively; the repeatability
      relative standard deviation (RSDr) ranged from 6.0 to 23.2% and the
      reproducibility relative standard deviation (RSDR) ranged from 12.0 to 69.4%. The
      multifunctional column coupled with a liquid chromatographic method for
      determination of aflatoxins in corn, almonds, Brazil nuts, peanuts, and pistachio
      nuts has been adopted first action by AOAC INTERNATIONAL.

PMID- 7819762
TI  - Determination of nitrate in vegetables by continuous flow: interlaboratory study.
AB  - A collaborative study for the determination of nitrate in leafy vegetables, such
      as endive, lettuce, spinach, and beetroot, by continuous flow (CF) was conducted
      by the Project Group on Collaborative Studies of the Inspectorate for Health
      Protection, Food Inspection Service, in The Netherlands. After extraction with
      water and filtration, samples were cleaned up by dialysis in the CF system.
      Extracted nitrates were reduced to nitrite in the system by metallic cadmium, and
      then the nitrite was reacted with sulfanilamide and N-1-naphthylethylenediamine
      to form a reddish-purple azo dye. This dye was measured colorimetrically at 530
      nm. Fourteen vegetable samples (including 7 blind duplicates) containing nitrate
      at ca 900 to 5200 mg/kg were analyzed singly by the proposed procedure by 13
      laboratories. The data were analyzed by the International Union for Pure and
      Applied Chemistry (IUPAC)-International Organization for Standardization (ISO)
      AOAC protocol for statistics. One collaborator was identified as an outlier for
      all results. For all samples analyzed, the repeatability relative standard
      deviation values varied from 1.7 to 5.5%, whereas the reproducibility relative
      standard deviation values ranged from 3.3 to 5.9%.

PMID- 7819763
TI  - Determination of ethyl carbamate in alcoholic beverages and soy sauce by gas
      chromatography with mass selective detection: collaborative study.
AB  - A method using gas chromatography with mass selective detection for the
      determination of ethyl carbamate (EC; also known as urethane) in alcoholic
      beverages and soy sauce was collaboratively studied by 17 laboratories including
      authors' laboratories. The method uses prepacked columns for extraction of
      liquids with methylene chloride, and n-propyl carbamate as the internal standard.
      A practice sample and 6 samples of distilled spirits, fortified wines, table
      wines, and soy sauces were analyzed by each collaborator. Each matrix included
      blind duplicates of incurred and fortified EC at 3 levels. Distilled spirits
      contained 50-330 ng EC/g (ppb), fortified wine 40-160 ppb, table wine 10-50 ppb,
      and soy sauce 15-70 ppb. The ranges of the repeatability relative standard
      deviations, excluding outliers, were 4.03-6.63% for distilled spirits, 4.01-5.05%
      for fortified wine, 3.94-6.73% for table wine, and 4.70-8.49% for soy sauce. The
      ranges of the reproducibility relative standard deviations, excluding outliers,
      were 8.53-9.49% for distilled spirits, 6.84-12.02% for fortified wine, 8.86
      18.47% for table wine, and 13.87-27.37% for soy sauce. Recoveries of added EC
      ranged from 87 to 93%. Recoveries relative to reference values, labeled as the
      internal standard, obtained by using gas chromatography/tandem mass spectrometry
      with a triple quadrupole mass spectrometer ranged from 89 to 100%.

PMID- 7819764
TI  - Decreasing the number of points in the standard curve for determining iron in
      flour: summary of collaborative study.
AB  - Seven laboratories participated in a collaborative study conducted to (1)
      evaluate the effects of reducing the number of points for the standard curve in
      the AOAC Official Method for iron in flour 944.02A-944.02C(a) from 10 points to 5
      points, and (2) compare the levels of iron found in foods by using the 10-point
      and 5-point standard curves. The 5 points (0.2, 0.6, 1.0, 1.4, and 1.8 micrograms
      Fe/mL) were selected by eliminating every other standard point from the 10-point
      curve after correction for the reagent blank. No differences in the performance
      parameters between method versions were found when blind duplicate analysis was
      used to estimate the performance parameters for each sample analyzed. Results
      from 2 laboratories were excluded from statistical calculations because of
      failure to follow the specific instructions to increase the dilution when sample
      absorbance readings exceeded the highest standard point reading. The 5-point
      standard curve has been adopted first action in method 944.02 by AOAC
      INTERNATIONAL.

PMID- 7819765
TI  - Determination of total phosphorus in foods by colorimetric measurement of
      phosphorus as molybdenum blue after dry-ashing: NMKL interlaboratory study.
AB  - A spectrophotometric method in which the sample is dry-ashed in the presence of
      zinc oxide, and total phosphorus content is measured colorimetrically as
      molybdenum blue was evaluated by 12 participating laboratories from the Nordic
      countries. The study included potato flour, sausage, cold ham, infant formula
      powder, cheese, and skimmed milk powder. The materials were presented to the
      participants as 12 randomly coded samples of 2 blind duplicates of each material.
      The phosphorus content of the materials varied between 0.076 and 0.96 g/100 g.
      The relative standard deviation for repeatability of the method varied from 1.1%
      for 0.96 g phosphorus/100 g to 5.4% for 0.29 g phosphorus/100 g. The relative
      standard deviation for reproducibility varied from 3.6% for 0.96 g phosphorus/100
      g to 7.7% for 0.23 g phosphorus/100 g.

PMID- 7819766
TI  - Gas chromatographic/mass spectrometric confirmation of ten N-methylcarbamate
      insecticides in liver.
AB  - A gas chromatographic/mass spectrometric (GC/MS) confirmation procedure for 10
      phenyl-N-methyl-carbamate insecticides in liver tissue was developed. The extract
      from liquid chromatography (LC) is purified with a C18 solid-phase extraction
      cartridge and then derivatized with heptafluorobutyric anhydride; the derivative
      is injected for analysis by GC/MS with electron ionization and multiple ion
      monitoring. The identity of the derivative is confirmed by comparison of its
      retention time and relative intensity data with those of a standard. Liver
      extracts from the LC procedure containing carbamates at 10 ppb levels were
      successfully confirmed by this procedure.

PMID- 7819767
TI  - Full scan confirmation of tetrahydrophthalimide in whole milk using gas
      chromatography/ion trap mass spectrometry.
AB  - The determination of tetrahydrophthalimide (THPI) in whole milk extracts by gas
      chromatography/ion trap mass spectrometry (GC/ITMS) in the full-scan, electron
      impact (EI) mode is presented. THPI is first isolated from whole milk by a
      procedure including protein precipitation, liquid-liquid partitioning, and 2
      solid-phase extraction (SPE) cleanup steps. GC/ITMS in the EI mode is used for
      the determinative step. The average recovery of THPI at fortification levels
      ranging from 5 to 54 ppb was 85.6% (n = 16, coefficient of variation = 9.13%).
      Full-scan mass spectral confirmation of THPI in milk extracts was obtained at the
      5 ppb fortification level. The limit of detection was estimated to be 0.5 ppb.
      Chemical ionization also was used for THPI determination in whole milk extracts.
      The simultaneous isolation and determination of captan and captofol in whole milk
      are also discussed.

PMID- 7819768
TI  - Development of a new series of agricultural/food reference materials for
      analytical quality control of elemental determinations.
AB  - Ten new Agricultural/Food Reference Materials--Bovine Muscle Powder (National
      Institute of Standards and Technology [NIST], code NIST RM 8414), Whole Egg
      Powder (NIST RM 8415), Microcrystalline Cellulose (NIST RM 8416), Wheat Gluten
      (NIST RM 8418), Corn Starch (NIST RM 8432), Corn Bran (NIST RM 8433), Whole Milk
      Powder (NIST RM 8435), Durum Wheat Flour (NIST RM 8436), Hard Red Spring Wheat
      Flour (NIST RM 8437) and Soft Winter Wheat Flour (NIST RM 8438)--were prepared by
      application of milling, irradiation, sieving, blending, and packaging procedures.
      Excellent material homogeneity was found for virtually all major, minor, and
      trace elements of interest. The reference materials were characterized with
      respect to elemental composition via an extensive international, interlaboratory
      characterization (certification) campaign. Chemical analyses conducted in 73
      cooperating laboratories applying 13 major classes of independently different
      analytical methods led to 278 concentration values for 34 nutritionally,
      toxicologically, and environmentally pertinent elements. A total of 213 best
      estimate and 65 informational concentration values are available for Al, As, B,
      Ba, Br, Ca, Cd, Cl, Co, Cr, Cs, Cu, F, Fe, Hg, I, K, Mg, Mn, Mo, N, Na, Ni, P,
      Pb, Rb, S, Sb, Se, Sr, Ti, V, W, and Zn. These products make a substantial
      contribution to the existing world repertoire of biological reference materials
      with respect to natural matrix and elemental composition. They are expected to be
      useful to analysts for quality control of analytical data. Applications include
      evaluations of analytical methods and instruments used in nutritional,
      toxicological, monitory, regulatory, environmental, agricultural, and other
      investigations. These products are available to the analytical community from the
      Standard Reference Materials Program, NIST, Gaithersburg, MD.

PMID- 7819769
TI  - Determination of tin in canned fruits and vegetables by atomic absorption
      spectrometry and liquid-liquid extraction.
AB  - A method was developed for the determination of tin based on the extraction of
      its 5,5'-methylenedisalicylohydroxamic acid complex with 1.09M isobutyl methyl
      ketone in tributyl phosphate. After the samples were treated with nitric and
      hydrochloric acid, the aqueous phase was made to 0.05M in perchloric acid. When
      the ratio of aqueous phase to organic phase was 4:1 (v/v), the detection limit
      and the relative standard deviation (n = 7, 50 micrograms tin) were 0.20
      microgram/mL and 0.9%, respectively. The proposed method was applied to the
      analysis of tin in canned fruits and vegetables. The results were in good
      agreement with those obtained by the phenylfluorone method.

PMID- 7819771
TI  - Determination of thiabendazole residues in pears by solid-phase
      spectrofluorimetry.
AB  - An analytical procedure for determination of thiabendazole (TBZ) residues in
      pears is described. The method involves extracting the chemical from the chopped
      fruit with buffer solution (acetic acidacetate, pH 4.6), use of Sephadex G-15
      dextrantype gel as a solid support, and determination of TBZ by solid-phase
      spectrofluorimetry (SPF). The relative fluorescence intensity of the Sephadex G
      15 gel-TBZ system, packed in a 1 mm-thickness silica cell, was measured directly
      at lambda ex = 303 nm and lambda em = 350 nm with a solid-phase attachment. The
      applicable concentration range was 5.0-20.0 ppb with a detection limit of 0.5
      ppb. Recoveries were from 98.7 to 102.0% when 15.0 ppb of TBZ was added to the
      fruit.

PMID- 7819770
TI  - Cleanup with two Florisil columns for gas chromatographic determination of
      multiple pyrethroid insecticides in products of animal origin.
AB  - A gas chromatographic method was developed for the simultaneous determination of
      9 pyrethroid insecticides in products of animal origin. The multiresidues of the
      pyrethroids in different samples were extracted with acetone-petroleum ether (1 +
      1), and extracts were cleaned up on a Florisil partition column and a Florisil
      adsorption column. Four animal tissue samples were examined at 0.05-0.25 ppm
      fortification levels. The average recoveries of all insecticides were 76.9-88.0%,
      and the coefficients of variation were < 4.6% for all insecticides except
      permethrin. The detection limits of the method were ca 5 ppb for all insecticides
      but permethrin, which had a detection limit of ca 10 ppb.

PMID- 7819772
TI  - Effectiveness of a one-day procedure for recovery of Salmonella from milk
      powders.
AB  - A rapid procedure for enumerating Salmonella in milk powders was evaluated. Dry
      whole milk and instant nonfat dry milk were rehydrated, artificially inoculated
      with various numbers of Salmonella cells, and stomached. Test portions were then
      treated with Tween 80 and pancreatic trypsin, and incubated for 1 h at 30 degrees
      C. The incubated test portions were centrifuged at 10,000 x g for 15 min at 5
      degrees C, and the resuspended pellets were plated on xylose lysine desoxycholate
      agar. The effectiveness of the procedure was expressed in terms of percentage
      recovery of the inoculum. The procedure, which was evaluated in 76 trials using 7
      Salmonella serovars, recovered < or = 73% of the inoculum for half of the trials
      conducted. Its effectiveness was dependent on the serovar, level of inoculation,
      and type of milk powder used.

PMID- 7819774
TI  - [Education and graduate education in the European Community].

PMID- 7819773
TI  - Reversed-phase liquid chromatographic determination of cromolyn sodium in drug
      substance and select dosage forms.
AB  - This study, presented as a technical communication, describes a reversed-phase
      liquid chromatographic method for select commercial formulations, namely,
      inhalation solution, nasal solution, capsule and inhalation aerosol.
      Miscellaneous validation parameters are also discussed.

PMID- 7819775
TI  - [Indications for ambulatory surgery].
AB  - Outpatient surgery demands a thorough evaluation of indication. It is of prime
      importance, influencing the entire problem of ambulatory operations. Although
      outpatient surgery is basically justified, the actual justification in any
      particular case is dependent upon the type and complexity of the operation as
      well as the anticipated postoperative situation. The decision to operate on an
      outpatient basis is an ongoing and dynamic process-it must take into
      consideration all the problems which might arise up to and even after discharge.
      An operation which is not specifically listed may still be performed on an
      outpatient basis if the individual circumstances justify this. The final decision
      will be determined by a number of factors, meaning that a strict list of
      indications is only of limited value.

PMID- 7819776
TI  - [Applications of forensic DNA technology in Gynecologic practice].
AB  - Genetic characterization of biological material in criminal cases and for
      parentage testing at the DNA level has gained wide acceptance. This paper
      describes the basic methodology of restriction fragment length polymorphism
      (RFLP) and the methodology based on the polymerase chain reaction (PCR). RFLP
      typing is performed in all cases where larger quantities of DNA are available
      because of its high discrimination power. PCR is used when only limited
      quantities of DNA or degraded DNA are available. There is a lot of
      applicabilities for the gynecologist, primarily in the investigation of sexual
      assault cases and in parentage testing of newborns, which is shown by several
      examples of forensic cases.

PMID- 7819777
TI  - [Histochemical characterization of endometrial proliferation using AgNOR
      (nucleolus organizer region)].
AB  - Nucleolar organizer regions (NORs) are loops of DNA that transcribe to ribosomal
      RNA. We used histochemical staining of NORs for 78 sections of endometrial
      tissue, obtained either from curettage or from hysterectomy specimens (normal
      endometrium 14, simple hyperplasia 10, complex hyperplasia 18, atypical
      hyperplasia 8 and adenocarcinoma 28). There was a significant positive
      correlation between mean AgNOR counts and the degree of hyperplasia. In
      adenocarcinoma, no significant difference was found between AgNOR counts in
      tissues of different histologic grades. Our study suggests that AgNOR counts are
      reliable markers of endometrial proliferation and allow a clear distinction
      between benign, premalignant and malignant epithelial changes.

PMID- 7819779
TI  - [An ectopic ureter with communication to the duct of Gartner and opening into the
      cervix--a rare cause of uncontrolled urine loss].
AB  - This is a report of a 22-year-old woman who suffered from a loss of urine via the
      vagina of unknown origin since childhood. The diagnosis of a left ureteral and
      renal duplication with an opening of an ectopic ureter into the cervix was
      established. Due to the result of the retrograde pyelogram we came to the
      conclusion that the opening into the cervix must have been via a segment of a
      Gartner duct. The ectopic system and the Gartner duct were completely removed by
      a combined abdomino-vaginal operation. Genesis, diagnostics, differential
      diagnostics and therapy of ectopic ureters are described.

PMID- 7819778
TI  - [Effect of different follicle puncture methods on hormone homeostasis in the
      woman. Studies within the scope of an in vitro fertilization-embryo transfer
      program].
AB  - Different methods for follicular puncture which were used in an in vitro
      fertilization-embryo transfer program have been analyzed in order to determine
      their influence on plasma levels of estradiol, progesterone, prolactin and beta
      endorphins. Thirty-eight patients awaiting oocyte aspiration were randomized into
      a laparoscopic (n = 20) and an ultrasound-guided oocyte aspiration group (n =
      18). No differences were observed as far as estradiol and progesterone levels and
      embryo transfer rates were concerned. When using the laparoscopic technique,
      prolactin levels were found to be elevated 1.5 times in comparison with the
      ultrasound-guided aspiration procedure, which is highly significant (p < 0.001).
      Also, beta-endorphins peaked at a significantly higher level during laparoscopy
      (27.8 vs. 20.7 mol/l, p < 0.001). The enhanced prolactin and beta-endorphin
      levels reflect an increased stress response during laparoscopy. With respect to
      less trauma and shorter duration of the procedure, we now perform the
      sonographically guided transvaginal aspiration technique in our program almost
      exclusively.

PMID- 7819780
TI  - [Acute pseudo-obstruction of the colon (Ogilvie syndrome) after Cesarean
      section].
AB  - In a 27-year-old woman a spontaneous perforation of the bowel developed after
      cesarean section. The clinical picture, pathophysiological aspects and
      prophylactic treatment of Ogilvie's syndrome are discussed. This rare but serious
      complication could have been avoided if the clinical picture and its simple
      conservative treatment had been known.

PMID- 7819781
TI  - [Why psychosomatic medicine will not become fashionable. Systematic constraints
      in medicine].
AB  - This paper compares two theoretical models of reality, showing the difference
      between classic and psychosomatic medicine and explaining why the classic
      approach is so attractive and successful: it satisfies the great human need to
      reduce complexity for eminently practical reasons. In contrast, the disadvantages
      of psychosomatics are described. They are due to its concept of professionalism
      which contradicts our traditional ideas of professional expertise. The
      contradiction forbids an integration of the two positions. So what are the
      chances of psychosomatic medicine?

PMID- 7819783
TI  - [Conservative therapy of incontinence].

PMID- 7819782
TI  - [Diagnosis of urinary incontinence in general practice].

PMID- 7819784
TI  - [Perioperative management in incontinence operations].

PMID- 7819785
TI  - [4th International Congress of Tropical Medicine in French Language. Martinique,
      15-18 November 1993. Proceedings].

PMID- 7819786
TI  - [Travel medicine].
AB  - Travel Medicine was inherited from Tropical Medicine and was organised around the
      development of intercontinental travels. It concerns all types of travellers,
      especially tourists, migrants and expatriates. It must be universal, scientific,
      but first of all preventive. Its aims to the information of all professionals
      concerned by health and tourism. Its goal is also the training of physicians and
      the education of travellers regarding their own responsibilities.

PMID- 7819787
TI  - [Plasmodium falciparum malaria in urban zones of high endemic regions in black
      Africa. Potential seriousness and possible preventive measures].
AB  - By the year 2000, 40% of the population of sub-Saharan Africa (western and middle
      Africa) will live in urban areas. It is obvious that urbanization reduces the
      transmission of malaria and make treatment easier. However, excessive optimism is
      inappropriate in regions where malaria transmission remains intense and where it
      is unfortunately illusory to hope for any major or geographically extensive
      reduction in transmission outside urban and suburban areas. In this context, the
      benefit of a reduction in malarial morbidity could be compromised by the
      increased risk of severe forms in town-dwellers, who now have little or no
      immunity, when they venture into the surrounding rural zone. The prevention of
      malaria during trips to endemic areas has become a reality for sub-Saharan
      African town-dwellers. We have to conceive and propose specific protective
      measures. This version of the advice to travellers about malaria, intended for
      use in Africa, is fairly similar, in theory, to the advice we give in Europe to
      travellers going to tropical areas: 1) at most, chemoprophylaxis throughout the
      exposure period plus 2 or 4 weeks after their return; 2) in all cases, protection
      against anopheles (take and travel with an impregnated mosquito net) and: 3)
      above all, the systematic and rapid treatment of any suspected attack of malaria
      (take and travel with a medicine pack containing antimalarials). If it seems vain
      to hope to be able to apply these measures in the current socio-economic
      situation in sub-Saharan African, they are nonetheless justified.

PMID- 7819788
TI  - [Environment and malaria in Burundi. Apropos of a malaria epidemic in a non
      endemic mountainous region].
AB  - In March 1991, an unusual increase of the consultations for fever and/or
      cephalgias was reported by the Health Centre of Muhanga. At the same time, the
      administrative authorities worried about the increase of death registration in
      some hills, located around the big swamp of Ruvubu, and next to this Health
      Centre. In this area, hypoendemic for malaria, the epidemic was belatedly
      recognized, entailing a gross death rate between 25.6 and 31.5/1000 person/year
      in 1991, in the three most hit hill-areas whereas this rate is 18/1000
      person/year for the national level. The initiation of the epidemic was favoured
      by the set up of Anopheles funestus and gambiae because of the modification of
      the hydro-agricultural milieu at high altitude, due to the extension of the
      ricefields and piscicultural ponds. Otherwise, there was a light rise of the
      medium temperature in this area in March 1991. In a non-immune population, the
      bouts of malaria were severe, especially in the age group from 0 to 4 years and
      in the pregnant women. By modifying the environment, the leaders of socio
      economic development programs must consider the consequences on the population's
      health and to make the health employees a partner in.

PMID- 7819789
TI  - [Imported dengue in france (1989-1993). Conditions to be met for assuring an
      accurate etiological diagnosis].
AB  - Every year, many travellers are going in endemic zone of dengue for more or less
      long stay. Back home, they show sometimes a feverish and algic syndrome reminding
      the dengue, and the confirmation of the diagnosis is required at the laboratory.
      In most cases, the impossibility to proceed to the isolation of the virus, the
      relative lack of specificity and the cross-reactions, that the available
      serological techniques do not allow to avoid, make delicate even impossible the
      interpretation of the results. A five-year assessment has nevertheless been
      attempted: it allows to establish that probably about several tens of dengue
      cases are imported each year in France. The conditions allowing to confirm
      biologically the clinical diagnosis are recalled and strict interpretation
      criteria are proposed.

PMID- 7819790
TI  - [Simultaneous vaccination against hepatitis A and yellow fever].
AB  - Simultaneous vaccination against hepatitis A and yellow fever has been studied in
      our unit: Sante-Voyage, Bordeaux. This randomised study included 108 healthy
      subjects: 36 received hepatitis A vaccine (Havrix, SKF), 36 received yellow fever
      vaccine and 36 received both. For hepatitis A vaccine protocol comprised one
      injection at day zero, one at D15, and one booster dose at 6 months. Those who
      received yellow fever vaccine had it at D0. Simultaneous vaccination is well
      tolerated and immunogenicity is as good as it is for each vaccine separately.
      This is particularly interesting for tropical travellers who are at risk for
      hepatitis A.

PMID- 7819791
TI  - [Pathology of travelers in the Antilles. Role of imported metropolitan
      pathology].
AB  - A preliminary and retrospective review--with a southern perspective--of some
      traveller's pathologies, mostly imported, and leading to hospital admission in
      Guadeloupe (FWI). End stage patients (cancer, AIDS...) frequently travel for a
      last, "compassional" trip. Ischemic heart disease is the leading pathology
      imported from the mother country (France). As well as in diabetes or psychiatric
      illness, destabilization frequently occurs as a consequence of travel (jet lag).
      Compulsive tennis plus dehydration cause the very common stone passage of
      nephrolithiasis. Concern is growing for heroin withdrawal syndrome or cocaine
      (crack)-abuse, and for supply for rare and expensive anticancer, antigraft
      rejection or antinfective (AIDS) agents. Much more familiar to us are
      photodermatitis, larva migrans, dengue, or ciguaterra, locally acquired. On the
      other hand some pathologies are quite "exotic" to us: Kaposi sarcoma, Lyme, or
      Behcet disease, familial mediterranean fever, brucellosis.

PMID- 7819792
TI  - [Infectious disease observed upon travel return. Retrospective and prospective
      investigation conducted in 1992 with 15 hospitals].
AB  - We report 1,302 cases of patients observed in the Department of Infectious
      Diseases in 15 French hospitals: 1,036 in a retrospective study in 1991; 266 in a
      prospective study in 1992. 48% of patients suffered from malaria, diarrhoea or
      hepatitis; 50% were admitted in the hospital. We have numbered 191 cases of non
      tropical diseases, 14 cases of HIV seropositivity and 14 cases of adverse events
      due to antimalarial chemoprophylaxis.

PMID- 7819793
TI  - [Real information needs of the traveller before his departure. Results of a
      survey by questionnaire].
AB  - This study is based upon 727 questionnaires completed by French travellers 10
      days after intercontinental travel. The response rate was 40%. Two out of 5
      travellers had generally mild health problems: fever (12%), diarrhoea (36%).
      Forty-six of them took drugs, which they had brought with them during their
      travel. Ten per cent had a satisfactory visit to a local physician. Medical
      informations given before departure appears to be sufficient, useful and relevant
      in more than 90% of cases. The traveller would like to receive them from his own
      physician or from vaccination centers. Other informations as insurance,
      assistance, administration, finances, appeared to have been incorrectly perceived
      by 20% of the travellers. The travel agent is the one who should provide adequate
      information. The traveller, in general, plans to do more travelling for his own
      well being if not for his work. Would not the bigger risk for him be "not to
      travel at all".

PMID- 7819794
TI  - [Development and trends from 1986 to 1993 of the attitude of intercontinental
      travellers on departure from France, with respect to malaria prophylaxis].
AB  - Simultaneously to information campaigns on malaria prevention in France, 5
      successive surveys were performed from 1986 to 1993 on the knowledge and
      attitudes of travellers regarding malaria prevention. French travellers
      (principally towards Sub Saharan Africa) know the risk of malaria and the
      measures of prevention (96%). Chimioprophylaxis using chloroquine has been
      progressively replaced by mefloquine and then by the association mefloquine
      proguanil; 25% of travellers know mosquito prevention measures (repellents and
      impregnated bed nets) and 27% know the stand-by treatment. Passive attitude of
      travellers has been modified (in part due to their education) and tend to
      emphasize today their own responsibility.

PMID- 7819795
TI  - [Multiple sclerosis in the black population].
AB  - Numerous epidemiological studies showed that The occurrence of multiple sclerosis
      (MS) was the result of genetic factors varying by ethnic group as well as
      geographical and environmental factors. It is difficult to estimate exactly the
      prevalence of MS among black Africans. Nevertheless it's possible to state that
      the disease is rare but present among those populations. Among black Americans
      prevalence of MS seems related to the degree of mixture with white population.
      Among West Indians the occurrence of MS is closely related to an environmental
      factor acquired in Europe before 15 years of age. Those data confirm the
      existence during childhood and adolescence of a critical period during which an
      environmental factor is acquired in regions of high prevalence for MS.

PMID- 7819796
TI  - [Paraplegia associated with HTLV 1 in Martinique. Study of 271 cases including 70
      with neuromuscular involvement].
AB  - To date, 271 cases of HTLV1-associated paraplegia have been observed in
      Martinique (French West Indies). The clinical picture consisted mostly in a
      spastic paraparesis or paraplegia with sphincter disturbances (80%) and lower
      limbs pains (60%). The severity of the disease appeared variable: after a mean
      disease duration of 6.5 years, 40% of the patients could walk without help, 35%
      used a single crutch, and 25% used a couple of crutches or were confined to a
      wheelchair. A variable neuromuscular component was observed in 70 cases (25.4%).
      In 38 cases, the peripheral signs (SIGNS) or the myositis were only mild. In
      contrast, 25 patients presented with severe amyotrophy evoking amyotrophic
      lateral sclerosis, and 7 other had features of dermatopolymyositis. Lastly, an
      extra-neural spreading of the disease was extremely frequent, including
      lymphocytic alveolitis (76%), sicca syndrome (69%) and more rarely uveitis,
      arthritis or vasculitis.

PMID- 7819798
TI  - [Dengue epidemic in New Caledonia (1989). Environmental factors and prevention].
AB  - An extensive dengue epidemic was reported in New Caledonia en 1989. Environmental
      factors (temperature and rainfalls) directly controlled the mosquitos population
      at the end of 1988. The introduction of a new dengue virus, transmitted by Aedes
      aegypti, was responsible for an epidemic that occurred in January-April 1989 and
      lasted until July 1989. The estimated number of cases was 25,000 and the attack
      rate was close to 120 per thousand inhabitants for a six month-period. The
      epidemic involved mainly the adult population in 84% of cases and 6-8% of
      patients was admitted in hospital with thrombopenia, leucopenia, minor
      haemorrhages in 2/3 of cases and 12 patients died with severe hemorrhagic disease
      or shock syndrome; initial serological results from suspected cases were positive
      against dengue by haemaglutination inhibition. Two dengue viruses were involved
      (dengue 1 and dengue 3) but dengue 3 was by far the most common. Ultra-low volume
      aerosols of diluted insecticide (decamethrine K'Othrine, Roussel) from road
      vehicles and aircraft was used from February to May to kill the adult mosquitoes
      (adulticiding). The efficacy dependent on the interaction of the insecticide and
      the flying mosquitoes is relative and debated but played probably a major role on
      the transmission, though the reduction of breeding sites was primarily uncovered.
      Since the epidemic, only sporadic cases were observed in 1991 and 1992.

PMID- 7819797
TI  - [Primitive Sjogren's syndrome in France and Ecuador. Possible involvement od HTLV
      1].
AB  - The authors study the possible involvement of retrovirus in Sjogren's syndrome.
      They report a preliminary study of 20 French and 13 Ecuadorian patients with a
      primary Sjogren syndrome. A previous epidemiologic study showed a HTLV1
      seroprevalence going from 0.04 to 6% on different regions of Ecuador. The results
      of this study show the presence of anti-HTLV1 antibodies only in 2 Ecuadorian
      patients and does not allow a final conclusion of the role of HTLV1 virus.
      Nevertheless other studies continue on the serie using minor salivary gland
      specimens obtained by biopsy. Recent publications and the notion of an "endogen"
      retrovirus will may be lighten a new day in this research.

PMID- 7819799
TI  - [Hemorrhagic dengue with shock in children in French Polynesia].
AB  - The dengue fever is an intertropical arbovirus, well known in French Polynesia
      where the first cases of dengue haemorrhagic fever appeared at the end of 1989.
      The authors report their experience in the paediatrics ward of the Centre
      Hospitalier Territorial (CHT) of Papeete, where, from 1990 to 1992, 310 cases of
      dengue fever have been registered with 79 cases of dengue shock syndrome (25.5%)
      and 12 deaths (4%). Then, following an epidemiologic summary and a description of
      how the clinical picture evolves in children, they insist on the fact that the
      pathophysiology of dengue fever is unknown, and there is no predictive factor;
      even if, in this study, the young age seems to be factor of severity. Therefore,
      an epidemiologic survey, and a very close monitoring of each case are necessary,
      in order to start an aggressive symptomatic treatment as soon as possible. The
      antivector's fight is still the only prevention against this arbovirosis.

PMID- 7819800
TI  - [Present status of zoonotic hemorrhagic fevers of South America].
AB  - Since 1958, the geographical distribution of Argentine hemorrhagic fever (AHF)
      has especially extended non only into the province of Buenos Aires but also
      towards the provinces of Santa Fe and Cordoba, leading to an estimated population
      at risk of about 1.2 M inhabitants. Recent epidemiological field studies has
      confirmed the major role of Calomys musculinus and C. laucha rodents in both
      transmission to man and conservation of Junin virus in nature. However, the human
      infection may result essentially from contacts with infected C. musculinus.
      Clinical condition of patients with AHF was greatly improved using AHF
      convalescent plasma and additional administration of vidarabin may still improve
      the results of treatment. A live attenuated vaccine, Candid No 1, is presently
      under evaluation in endemic foci of AHF. On the contrary Bolivian hemorrhagic
      fever (BHV) appears at present quite silent. A new disease resembling both AHF
      and BHF, the Venezuelan hemorrhagic fever, appeared in 1989 in the rural areas of
      central Llanos of Venezuela. The mortality was very high, reaching 23% or more
      among severely ill patients. The wild small rodents responsible for the disease
      were identified as Sigmodon alstoni and Zygotontomys brevicauda. Recent extension
      of agricultural practices and massive immigration may probably explain the recent
      emergence of this new viral zoonosis.

PMID- 7819801
TI  - [Current situation of yellow fever in Latin America].
AB  - Yellow fever endemicity is currently stabilized in South America: an average of
      115 cases has officially been notified each year since 25 years (between 12 and
      304 annual cases). These figures are underevaluated but no epidemic has been
      observed since 1983. Only sporadic or limited grouped cases have been reported.
      All declared cases correspond to people who have been infected within sylvatic
      areas, mainly adult forestmen. Within the last years, the majority of cases have
      occurred in Peru and Bolivia; the other cases have been observed in Brazil, in
      Columbia, in Ecuador and in French Guiana (imported strains from Surinam). This
      apparently low virus circulation may be due to massive campaigns of vaccination
      and to mosquito vector control. But this situation could suddenly reverse as
      observed in the past with yellow fever and the spring of the urban Aedes aegypti
      vector. Genetic and immunochemical heterogeneity has been demonstrated between
      South American and African yellow fever strains, which may reveal evolutionary
      divergence due to different ecological environment between the two continents.
      Yellow fever definitely remains a topical disease which requires a constant
      surveillance.

PMID- 7819802
TI  - [Epidemiological characteristics of HIV infection in Martinique].
AB  - The epidemiologic study of HIV infected patients in Martinique from 1985 to 1992
      allowed to point out a stability of new cases by year, and confirm the
      heterosexual transmission in this area. The sexual comportment of Martinicans
      seems to be different of the continental French people and different between men
      and women. This constation is important to know for the preventive strategy of
      the infection.

PMID- 7819803
TI  - [Introduction to water and the environment. Threat to drinking water].

PMID- 7819805
TI  - [Typhoid fever in South Vietnam, 1990-1993].
AB  - In South Viet-nam, typhoid fever remains a considerable intestinal infection.
      Between 1990 and 1993, among 15 districts in the South of the country, a total
      per year of 3,853 to 9,179 cases was registered: from 8 to 31 led to death.
      Recently a large epidemic of typhoid fever broke out in the An Minh district
      (territory of KienGiang, South Viet-nam), affecting 3,049 people and bringing on
      two cases of death. Among the 574 blood samples, 266 strains of S. Typhi, 22 S.
      Paratyphi A and 2 S. Choleraesuis have been isolated. Our investigations on the
      spot led to some epidemiologic and clinical reflexions and enabled us to estimate
      the effectiveness of quinolones (?) in the treatment for typhoid fever. The
      epidemic may be ascribed to different causes: lack of pure water supply in rural
      area; fecal pollution caused by inhabitants of this endemic area defecating
      directly in the waterways; ingestion of contaminated food, especially vegetables
      sprayed with polluted water; quite low level of public sanitation and individual
      hygiene. Clinically, the disease consists in prolonged fever, with digestive
      disorders (anorexia, diarrhoeae, diffuse abdominal aches). Splenomegalia and
      hepatomegalia are inconstant. The dissociation of the pulse from the temperature
      is not frequent and the rosy spots are rare. The antibiogramm applied on the
      isolated strains of S. Typhi revealed their resistance (R) to usual antibiotics
      (chloramphenicol, ampicillin, Bactrim), but S. Typhi is very sensitive to
      quinolones (ofloxacin, fleroxacin, R = 0).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7819804
TI  - [Diarrheic diseases in children. Rationalization of fecal test].
AB  - The level of diarrheic diseases among children in Burkina Faso is very high. The
      identification of aetiologic agents of diarrhoea in hospitalized children (0-36
      months) is one of the objectives of the study. All children less than 37 months
      old admitted to the Pediatric Unit of the National Hospital Souro Sanou of Bobo
      Dioulasso between January 1990 and March 1991, were investigated by a
      standardized clinical examination, and in addition, we do an analysis of a rectal
      swab at admission and a stool to identify aetiologic enteric agents. As a
      conclusion to the study: an agent was isolated in 56% of the children with
      diarrhoea, and in 40% of the children without diarrhoea; some germs (such
      Salmonella, Shigella, Entamoeba) are found in children both with and without
      diarrhoea; also, the total of these examinations comes to 20 US $ per episode, or
      100 US $ per children/year in Burkina Faso where the number of bouts reaches 5
      times per year per infant who is less than 5 years old. Stool samples are not
      beneficial for children with diarrhoea, neither for the diagnosis nor for the
      treatment. There fore these types of routine exams should not be used in Sub
      Saharan Africa.

PMID- 7819806
TI  - [Water and viral hepatitis].
AB  - The main agents responsible for acute viral hepatitis throughout the world are
      the hepatitis A virus (HAV) and the hepatitis E virus (HEV). Both are transmitted
      by fecal-oral route and can provoke large epidemics, HAV in developed countries
      and HEV in developing countries. Water is a major vehicle of spread. However, two
      different epidemiological patterns have to be distinguished: level of HAV
      excretion is short but high. Because of its resistance to physical and chemical
      agents, HAV remains infectious for a long time under environmental conditions.
      Progress in hygiene have nearly stopped the circulation of HAV in industrialized
      countries, making populations more susceptible to the infection and increasing
      the epidemic risk. Conventional measures sometimes fail to prevent HAV
      infections. Vaccine is currently the best way for hepatitis A prophylaxis; HEV is
      excreted briefly and at low concentrations. Viral particles are fragile in vitro
      and their viability in environment is not yet understood. Epidemics mainly occur
      in countries with poor sanitary conditions, resulting from heavy water
      pollutions. High case-fatality rates are observed, especially among pregnant
      women. The control of enterically transmitted viral hepatitis remains a major
      public health challenge. Virological surveillance of waste water could improve
      strategies based on hygiene, sanitation and supply of drinking water.

PMID- 7819807
TI  - [Human protothecosis and environment].
AB  - Protothecosis are uncommon infections caused by Prototheca, considered to be
      achlorophylous algae. Nearly 80 human cases are reported in the literature since
      the first case described by Davies and Wakelin in 1964 in Sierra Leone (11). The
      disease have been identified in Europe, Asia (Japan, Thailand, China), Oceania
      and in the United States with 40 cases, particularly in the Southeast.
      Clinically, three clinical manifestations can be observed: 1) cutaneous lesions:
      papules, plaques or eczematoid, papulo-nodular areas of the extremities, 2)
      olecranon bursitis which occurred in 25% of cases, 3) systemic protothecosis. An
      immunosuppressive factor local or general can be found in half of the cases and
      the first description of algal meningitis was reported in a patient with AIDS in
      association with Cryptococcus neoformans. Because the disease is clinically not
      suspected, the diagnosis is often provided by histology showing a dermic
      granuloma with endospores. The characteristic feature of protothecosis in tissues
      is the presence of specific mature sporangia of Prototheca wickerhamii with the
      pattern of morula. The organism was PAS, Grocott and mucicarmin positive. The
      ecology was studied by Clark (7), Pidoux (23), Pore (25) and Sudman (27).
      Prototheca are ubiquitous inhabitants of sewages and are found in slime flux and
      animal wastes contaminating different aquatic systems. The transmission generally
      occurred by traumatic inoculation. Prototheca are also found in the digestive
      system of man and animals without never invasion of the epithelium and mucosae in
      experimental models. The pathogenicity and virulence are moderate and they are
      considered as rare opportunistic agents.

PMID- 7819808
TI  - [Javelle water and drinking water].
AB  - Because of its exceptional disinfecting properties, hypochlorite bleach is, along
      with vaccines and antibiotics, an outstanding tool in the prevention of water
      borne infectious diseases such as cholera, and especially in tropical
      environments. In addition, hypochlorite bleach is available around the world, and
      at low cost. Moreover, hypochlorite bleach is safe for human when used as
      directed. It is also sale for the environment in household use. In the Public
      Health domain, hypochlorite bleach with its 200-year history remains both a
      modern product and a product of the future.

PMID- 7819809
TI  - [Malaria in Vietnam. Environment, prevention and treatment].
AB  - In Viet-nam, malaria rages in mountainous and wooded areas, as well as in coastal
      areas. In these geographical zones, the diversified features of environment have
      different repercussions on the development of Anopheles species. The main vector
      species have strict oecological requirements: An. dirus, disseminated in the
      forests, colonizes stagnant and shaded water, such as rain water collected in
      ground dips and in cavities of trees and rocks; An. minimus selects its breeding
      sites in pure and slightly current streamlets, in the hilly areas. On the
      contrary, An. sundaicus, first-rate coastal vector, adjusts itself to diversified
      biotopes, which nevertheless all have common features: saltiness of water
      (optimum 1-7 g NaCl/litre), faint sunning, stagnant or slightly current water,
      with floating green algae (Ceratophyllum, Najas). P. falciparum prevails in the
      wooded areas (P. f.: 75%; P. v.: 25%); but in the coastal areas where Anopheles
      hyrcanus pullulates, P. vivax reaches the same ratios as P. falciparum. In Viet
      nam, the prevention and antimalarial fight are centred on three measures:
      diagnosis, treatment and watching of diseases, antivectorial fight, antimalarial
      fight combined with first medical care. Owing to the spreading of P. falciparum
      chemoresistance to chloroquine (27 to 76%) and to Fansidar (22 to 83%), we had to
      have recourse to new antimalarials: artemisinine and artesunate tested in several
      regions of the country (tests in vitro and in vivo during 28 days) revealed their
      high schizonticidal capacity, but the recrudescence reached 30 to 50%.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7819812
TI  - [Prurigo in tropical area. Importance of its association with HIV infection].
AB  - The term prurigo applies to a classic chronic skin disease of children (P.
      strophulus) which is becoming found very seldom in developed countries, but
      remains extraordinarily prevalent in tropical areas. This striking geographical
      distribution relies on its ectoparasitic origin. Some peculiar aspects of
      prurigo, observed in French Guyana (South America), are reported. The original
      point is a new aspect of adult acquired prurigo, associated with HIV infection,
      which appears to be one of the features characteristic of tropical AIDS. This HIV
      associated prurigo (HAP) is the revelating event, in as high as 20% of HIV
      infected people, significatively those with less than 200 CD4 cells. HAP appears
      as a marker of HIV infection with poor sensitivity, but much higher specificity
      (92%), with no correlation with acquisition's risk factors. Just like infantile
      prurigo, HAP can be considered an arthropod bite reaction which seems to be
      enhanced in HIV infected people living in tropical environment.

PMID- 7819811
TI  - [Natural murine infestation by Angiostrongylus costaricensis Morera and Cespedes,
      1971 in Guadeloupe].
AB  - In 1992, two cases of abdominal angiostrongylosis were reported in young
      Guadeloupean children. With a view to determine the natural infestation rate of
      Guadeloupe rodents (Rattus rattus, R. norvegicus) by Angiostrongylus
      costaricensis, 656 rats caught in the country have been examined. Both murine
      species are naturally infested (6.2% in R. rattus and 14.9% in R. norvegicus),
      which gives a total prevalence of 7.5%. This total prevalence is higher in the
      tourist area. A complementary investigation proves to be necessary to identify in
      Guadeloupe the alleged intermediate hosts (slugs, land snails) in which the human
      illness has its direct origins.

PMID- 7819810
TI  - [Early treatment of attacks of pernicious malaria with artemisinine per os].
AB  - 416 cases of P. falciparum cerebral malaria are treated with various anti-M
      drugs: mortality rate is 25% with quinacrine, 12.3%; quinine alone, and 10.1%
      with quinine associated to sulfonamide. During 1991-1992, artemisinin per os is
      used in the early treatment of 21 cases of cerebral malaria, in according to
      propose a regimen practicable at primary health care units, where parenteral
      injection is sometimes unavailable: coma clearance after 14-21 hours in 100%,
      fever clearance after 54-97 hours in 100%, and parasite clearance in 100% after
      101 hours; no case of death is found.

PMID- 7819813
TI  - [Pasteur's theories on the environment].

PMID- 7819814
TI  - The role of fludarabine in hematological malignancies.
AB  - Fludarabine monophosphate, a synthetic nucleoside analog, has been shown to have
      considerable activity in a number of lymphoid malignancies. In chronic
      lymphocytic leukemia the response rates can exceed 70% with a considerable
      proportion of complete remissions being attained. These rates are markedly
      superior to earlier therapies with which complete remission was uncommon. It also
      has significant activity in previously treated patients for whom effective
      salvage regimens were unsatisfactory. In addition, fludarabine shows substantial
      activity in low grade non-Hodgkin's lymphoma, both as initial treatment and as
      salvage therapy. Fludarabine is effective in Waldenstrom's macroglobulinemia and
      is active in other low grade lymphoid malignancies. Major toxicities are
      reversible myelosuppression and depletion of T lymphocytes. The use of
      fludarabine in hematological malignancies will be reviewed, with reference to its
      mode of action and future use in combination therapies.

PMID- 7819815
TI  - Monoclonal gammopathy of undetermined significance.
AB  - Monoclonal gammopathy of undetermined significance (MGUS) accounted for 56% of
      the 1026 patients with a monoclonal plasma cell disorder seen at the Mayo Clinic
      during 1992. Approximately 3% of persons older than 70 years and 1% of those
      older than 50 years had MGUS. In a series of 241 Mayo Clinic patients with a
      serum M-protein but no evidence of multiple myeloma, macroglobulinemia, primary
      amyloidosis, lymphoma, or related disorders, followed up for 20 to 35 years
      (median, 22 years), the condition of 19% remained stable. Ten percent had an
      increase in the serum M-protein to 3.0 g/dL or more but did not require
      chemotherapy, whereas 47% died of unrelated causes. 59 of the 241 patients
      (24.5%) developed a serious disease during the median follow-up period of 22
      years: multiple myeloma in 39 patients, primary amyloidosis in 8, Waldenstrom's
      macroglobulinemia in 7, and other malignant lymphoproliferative disorders in 5.
      The actuarial rate of malignant transformation was 17% at 10 years and 33% at 20
      years. The median interval from diagnosis of MGUS to the diagnosis of serious
      disease was 8.5 to 10.5 years. No single factor can differentiate a patient with
      benign monoclonal gammopathy from one in whom a malignant plasma cell disorder
      will subsequently develop. Therefore, the serum M-protein must be measured and a
      clinical evaluation conducted periodically.

PMID- 7819816
TI  - Use of single donor platelets.
AB  - Advances in apheresis technology have made single donor platelets easier to
      obtain and therefore more plentiful. There are some hypothesized advantages to
      single donor platelets including reduced disease transmission, reduced
      alloimmunization, and superior function and storage characteristics. These ideas
      have swayed some to insist that single donor platelets should become the routine
      platelet transfusion component. While support exists for some of these benefits,
      there is no consensus that the risks to donors, the difficulties of setting up a
      program, and the expenses are sufficiently outweighed that the conversion of
      blood banks to a single donor platelet supply is merited. The major advantage to
      single donor platelets is that the selection of certain donor characteristics,
      such as HLA compatibility, is facilitated since a total dose of platelets is
      coming from one donor.

PMID- 7819817
TI  - Review of neonatal red cell transfusion practices.
AB  - In the United States in 1991, 290,000 or 7.1% of the 4,110,907 live births were
      premature infants; 53,299 or 1.3% were infants with birth weights of less than
      1500 grams. Many if not all of these very low birth weight infants will require
      red blood cell transfusions for one of several reasons. These include exchange
      transfusions for hyperbilirubinemia, but most often transfusions are simple small
      volume transfusion also called 'topper' transfusions. Most of these small volume
      transfusions are given for iatrogenic blood loss or 'bleeding into the
      laboratory.' Studies have demonstrated that the sicker the infant, the more blood
      sampling is needed and the greater the exposure to red blood cell (RBC), platelet
      and plasma products. Simple RBC transfusions may also be given for specific
      clinical indications or to maintain a predetermined hemoglobin concentration.
      This manuscript will review the criteria for RBC transfusion in neonates and
      selection of product as regards anticoagulant and specialized processing. In
      addition, the results of recombinant erythropoietin (r-EPO) clinical trials in
      neonates will be discussed.

PMID- 7819818
TI  - Autologous bone marrow transplantation in acute lymphoblastic leukaemia.
AB  - There has been a great deal of interest in the use of high dose chemotherapy
      and/or radiotherapy, with autologous bone marrow/peripheral blood stem cell
      rescue, in the treatment of haematological malignancies including acute
      lymphoblastic leukaemia (ALL). In this review we assess the role of autologous
      bone marrow transplantation (ABMT) in ALL. The heterogeneity of this disease
      makes the analysis of treatment results in ALL difficult to interpret. There is
      some evidence that ABMT may be useful in second complete remission (CR) and
      increasing interest in ABMT as a therapeutic option in first CR in adults. At the
      moment there is little evidence that such an approach will have an impact in
      childhood ALL. ABMT is considerably less toxic than allogeneic bone marrow
      transplantation and the major cause of 'treatment failure' is disease relapse.
      There has been considerable effort put into purging autologous bone marrow of
      malignant stem cells but whether purging is effective remains controversial and
      not proven. Newer studies involving cytokines post-ABMT to stimulate an
      artificial 'graft versus leukaemia' effect may prove of value.

PMID- 7819820
TI  - Quality of current diagnostic performance--our most serious health care quality
      problem?

PMID- 7819821
TI  - Commentary: diagnosis tracking and health reform.
AB  - Monitoring and feedback of diagnostic errors is essential for quality diagnosis
      and inimical to the direction in which the United States health delivery system
      is heading. Tracking diagnosis evolution longitudinally can provide rich clinical
      insights to improve the timeliness and accuracy of diagnosis, yet we lack even
      primitive systems to accomplish this function. Ten examples are listed,
      illustrating key questions regarding misdiagnosis. A system for tracking
      admitting diagnosis revision is presented as a primitive diagnosis tracking
      prototype. An automated system is required to generalize this system to a
      longitudinal outpatient setting. The perils in the implementation of diagnosis
      tracking include the potential for fear-inducing punitive application, tampering
      with appropriate diagnostic strategies due to failure to distinguish common from
      special cause variation, and the affixing of "price tags" to diagnoses. The
      latter is an especially worrisome side effect of market-driven health reform, and
      threatens the success of the project.

PMID- 7819819
TI  - Prophylaxis against late infection following splenectomy and bone marrow
      transplant.
AB  - There is a well documented risk of late infection following both splenectomy and
      bone marrow transplantation. In asplenic patients, the phagocytic and antibody
      producing roles of the spleen are lost and there is a lifelong susceptibility to
      infection which may be overwhelming and fatal. Patients most at risk are
      children, those with underlying lymphoproliferative disorders and those receiving
      immunosuppressive therapy. Although it is hard to prove benefit from preventative
      strategies, patients are likely to benefit from prophylactic antibiotic therapy
      and from immunisation with pneumococcal, Haemophilus influenzae-B and
      meningococcal vaccine given prior to splenectomy. Following an allogeneic bone
      marrow transplant (BMT), recovery of immune function takes up to a year. During
      this time, patients are at high risk from cytomegalovirus (CMV) and varicella
      zoster virus (VZV) infections and also from pneumocystis pneumonia. Prophylactic
      medications are used to good effect. The major threat of late infection occurs in
      patients with chronic graft versus host disease (cGVHD)--there is increased
      susceptibility to bacterial, fungal and viral infections. Many patients without
      cGVHD recover immune function fully and many develop antibodies to specific
      recall antigens. This does not occur in all patients and although there is a low
      risk of infection with organisms against which vaccines are available. If it is
      not possible to measure specific antibody titres and consequently offer selective
      re-immunisation, then a universal vaccination strategy should be in force.
      Response to vaccines is likely to be poor before one year post BMT. For
      autologous transplant recipients, immune recovery is probably complete and
      routine re-immunisation is not likely to offer much benefit. For both asplenic
      and bone marrow transplant patients, education of patient and physician is
      important.

PMID- 7819822
TI  - Conformance of clinical practice to established recommendations for the diagnosis
      and treatment of venous thromboembolic disease: Robin revisited.
AB  - Over a decade ago, Dr. Robin expressed concern regarding overdiagnosis and
      overtreatment of pulmonary embolism. Since that time, significant advances have
      been forthcoming in the diagnosis and treatment of venous thromboembolic disease.
      Using Continuous Quality Improvement concepts, this study revisits Robin's
      concerns and assesses the conformance of clinical practice at one institution
      with established requirements for the diagnosis and treatment of venous
      thromboembolic disease to identify remaining opportunities to improve care. The
      study design is a retrospective chart review. Medical records of all patients (N
      = 63) discharged from a university-affiliated teaching hospital from 7/1/89 to
      6/30/90 with a diagnosis of primary venous thromboembolic disease were studied.
      Requirements for the diagnosis and treatment were established through review of
      the medical literature. Conformance to these requirements was assessed and
      described. Descriptive statistics were used. Only 7 of 63 charts (11%) met all
      requirements for the diagnosis and treatment of venous thromboembolic disease.
      Fifty-six charts (89%) failed to meet at least one criterion. There was no
      evidence of overdiagnosis of venous thromboembolic disease in patients with a
      discharge diagnosis of pulmonary embolism (N = 17). Eight of 62 patients (13%)
      demonstrated potential overdiagnosis of venous thromboembolic disease involving
      the lower extremities. Nine of 60 (15%) heparin therapies demonstrated
      significant nonconformance to recommendations. Fifty-four of 59 (91%) warfarin
      therapies failed to conform to recommendations. Eighty-three percent of these
      warfarin errors were considered to be technical. However, 17% were determined to
      be clinically significant. Of 5 patients treated with a transvenous filter
      device, 1 failed to meet therapeutic requirements. No patients received
      thrombolytic therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7819823
TI  - Bayesian analysis in the diagnostic process.
AB  - A diagnosis is made by a process in which the physician gathers evidence. The
      physician uses this evidence to put the patient in a class of patients with a
      disease. Bayes' theorem quantifies the effects of the evidence in increasing the
      probability that the patient has the disease. This article will discuss the
      potential of Bayesian analysis for medical diagnosis. Applications of Bayesian
      analysis to the diagnostic process could improve the efficiency of this process.

PMID- 7819824
TI  - Quality improvement and public health--tetanus immunization in the emergency
      department.
AB  - The administration of tetanus toxoid vaccine to both adults and children
      represents an often neglected, but medically necessary procedure for patients who
      receive traumatic injuries to nature's natural surface barrier, the skin. While
      performing retrospective chart reviews, the collaborative practice environment
      fostered in the Emergency Department at Reston Hospital Center, (wherein the
      physician and nursing staff are schooled in Deming's Quality Improvement-FOCUS
      PDCA-methodology, and the concepts of "patient care clinical process ownership,"
      and "professional job enlargement and job enrichment" diffuse throughout the
      Emergency Services Systems design), identified a potential problem with tetanus
      immunization related to existing standing orders. Initial data collection
      utilized count-between methodology. Over a 31-day period, 216 patients who
      required tetanus immunization were identified. Appropriate tetanus toxoid
      administration was "missed" 20 times, with a median of 9 appropriate tetanus
      immunizations before an administration was "missed." Flow chart analysis of the
      tetanus toxioid administration process identified the sources of variation of
      that process. A pilot PDCA cycle was instituted to redefine the process, control
      the variability, and measure the results. Upon completion of the third PDCA cycle
      of 31 days, 367 patients were identified who required tetanus immunization.
      Appropriate tetanus toxoid administration was "missed" 3 times with a median of
      120 appropriate tetanus immunizations before an administration was "missed."
      Conclusions include: a) The appearance of special cause variation, (diaster
      situations), must be recognized as having the potential to disrupt healthcare
      process improvements.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7819826
TI  - Inappropriate clinical care in nursing homes.

PMID- 7819825
TI  - Blood transfusion and blood conservation: cost and utilization issues.
AB  - Approximately 12 million red blood cell units are transfused to nearly 4 million
      patients annually in the United States (1). The conservation of blood has
      historically arisen from awareness that the inventory of this resource is limited
      (2), as well as the knowledge that blood transfusion carries a risk (3).
      Estimates of current blood transfusion risks (4-12), and the costs of transfusion
      complications (13-17), are summarized in Table 1. In addition, emphasis on the
      costs of health care has raised issues related to the costs of blood transfusion
      (18, 19). Finally, recent guidelines have emphasized that in the elective
      transfusion setting, no blood transfusion is a desirable outcome (20, 21).
      Furthermore, these guidelines along with consensus conference recommendations
      (22) have emphasized that if blood is to be transfused, autologous (the patient's
      own) blood is preferable to allogeneic (from an anonymous, volunteer donor)
      blood. Thus, the costs of blood conservation, for which an increasing array of
      technologic procedures and products have become available (Table 2), have also
      become an issue (23). The purpose of this review is to provide an overview of
      emerging data on the cost-effectiveness of blood and blood conservation
      interventions in order to help identify areas important for future investigation.

PMID- 7819827
TI  - Urinary excretion of pyridinolines crosslinks measured by immunoassay and HPLC
      techniques in normal subjects and in elderly patients with vitamin D deficiency.
AB  - Hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) are specific
      constituents of mature skeletal collagens excreted in urine. Their measurement
      represents a sensitive index of bone resorption. In this study, we have measured
      urinary excretion of pyridinolines crosslinks by immunoassay (ELISA) and HPLC
      methods in 80 patients with different bone resorption rates. We chose a sample of
      44 healthy adults (30 men and 14 women) and a sample of 36 elderly patients (7
      men and 29 women) presenting a secondary hyperparathyroidism due to a vitamin D
      deficiency. The correlation between HPLC (x) and ELISA (y) was judged
      satisfactory (y = 0.794x + 6.947, r = 0.92). The sensitivity of pyridinolines
      estimation was 50 nmol/l for immunoassay and 20 nmol/l for HPLC. The intra-assay
      and inter-assay coefficients of variation for the two analytical methods was <
      10%. The mean excretion of crosslinks (nmol/mmol of creatinine) measured by both
      methods in the sample of healthy adults was higher in women than in men. The
      amount of pyridinolines crosslinks excreted by elderly patients with vitamin D
      deficiency are three time higher than those of normal adults when measured by
      ELISA and HPLC methods. The distribution of different molecular forms of urinary
      pyridinoline crosslinks was investigated. Values of pyridinolines measured by
      HPLC in our samples of elderly patients have shown that free and peptide-bound
      pyridinolines with molecular weight (mol. wt.) smaller than 1000 Da represent
      approximately 80% of the total pyridinolines contained in urinary samples. A
      study on the evaluation of the antiserum used in the immunoassay for reacting
      with the different molecular forms isolated from urine showed a high affinity for
      free and peptide-bound pyridinolines with molecular weight smaller than 10,000 Da
      and that do not react strongly with peptide-bound with molecular weight greater
      than 10,000 Da. We conclude that, although this immunoassay does not measure
      total pyridinolines and does not distinguish between HP and LP, it seems
      convenient for diagnostic of metabolic bone diseases.

PMID- 7819828
TI  - Age dependence of the normal/abnormal difference of bone mineral density in
      osteoporotic women.
AB  - Bone mineral density (BMD) is the major factor in bone strength and in the risk
      of suffering osteoporotic fractures. The aim of this study was to examine the
      normal/abnormal difference for antero-posterior (AP) spine, lateral spine,
      proximal femur and total body BMD to assess if age influences discrimination at
      three different decades between 50 and 80 years of age. The BMD was determined in
      61 control women and 60 osteoporotic women (at least one vertebral wedge fracture
      readily visible in the lateral X-rays of the thoracic or lumbar spine).
      Measurements were made by DEXA with a total body scanner. The BMD of the whole
      group of osteoporotic women was markedly lower than that of age-matched controls
      at all skeletal areas (P < 0.001) except at the arms where the difference was
      smaller (P < 0.02). The Z-score (the difference between osteoporotic patients and
      age-matched control divided by the intrapopulation S.D.) was similar
      (approximately -1.7) over the AP spine, femoral neck, Ward's triangle, total body
      and legs. It was significantly lower at the arms (-0.8, P < 0.001), lateral spine
      (-1.4, P < 0.01) and trochanter (-1.3, P < 0.001) compared with the Z-score of
      the AP spine. The analysis of the results by decades of age disclosed that the
      higher Z-score on the 6th and 7th decades corresponded to the AP lumbar spine
      (approximately -2.0). A high descrimination was also observed for the femoral
      neck, Ward's triangle and legs while the Z-score of the lateral lumbar spine,
      total body, trochanter and arms were significantly lower than that of the AP
      lumbar spine. However on the 8th decade the Z-score of the AP lumbar spine
      diminished to -1.2 and was only significantly higher than the Z-score of the arms
      (P < 0.01). The study showed that, in women 50-60 years of age--the period where
      the majority of studies are made for prevention of osteoporosis, none of the
      other skeletal areas were superior to the AP spine in discrimination for spinal
      osteoporosis. Proximal femur and legs densitometry gave lower but not
      significantly different Z-score than the AP spine, while the remaining areas were
      significantly inferior to AP spine in separating osteoporotic and normal women.

PMID- 7819829
TI  - Effect of 1-hydroxyethylidene-1,1-bisphosphonate on membrane-mediated calcium
      phosphate formation in model liposomal suspensions.
AB  - The bisphosphonate, 1-hydroxyethylidene-1,1-bisphosphonate (HEBP), was examined
      for its effect on calcium phosphate precipitation in pH 7.4, 22 degrees C
      suspensions of 7:2:1 PC:phosphatidylcholine (PC):dicetylphosphate
      (DCP):cholesterol (Chol) and 7:1:1 PC:phosphatidylserine (PS):Chol liposomes.
      HEBP (0.5-50 mumol/l) in the suspending medium had little, if any, effect on
      precipitation that formed inside phosphate-rich (50 mmol/l) aqueous interiors of
      liposomes as a result of ionophore (X-537A) driven 2.25 mmol/l Ca2+ influxes from
      the medium. On the other hand, HEBP had a significant negative impact on the
      subsequent spread of the precipitate into the surrounding medium when the latter
      was made metastable with 1.5 mmol/l total inorganic phosphate (PO4). The
      inhibitory effect of HEBP was more strongly felt in the 7PC:1PS:1Chol liposomal
      suspensions, with only 1 mumol/l HEBP needed to effectively block extraliposomal
      precipitation compared to 7.5 mumol/l for 7PC:2DCP:1Chol suspensions. Direct
      encapsulation of HEBP (1-1000 mumol/l) together with PO4 in the aqueous cores of
      7PC:2DCP:1Chol liposomes reduced somewhat (approximately 30%) intraliposomal
      yields and delayed but did not block extraliposomal precipitate development.
      These results provide a possible physicochemical explanation for the suppression
      of matrix vesicle initiated mineralization in ectopically-induced osteoid tissue
      of HEBP treated mice [1]. In particular, the liposome results suggest that
      membrane phosphatidylserine interactions with mineral may enhance HEBP's
      effectiveness in vivo.

PMID- 7819830
TI  - Effect of cyclosporine A on normal human osteoblasts in vitro.
AB  - Cyclosporin-A (CsA) inhibits in vitro proliferation of non-human tumour-cloned
      osteoblasts. Our aims were to study the direct effect of CsA on proliferation of
      normal human osteoblast (NHOb) cultures and to ascertain whether CsA-treated
      patients' sera (CsATPS) may exert effects on the osteoblast which differ from the
      direct effects of CsA. We studied tritiated thymidine ([3H]thymidine)
      incorporation in NHOb cultures incubated with (a) increasing CsA concentrations
      (1.2 to 4800 ng/ml), (b) the same concentrations as in the previous experiment
      but with the addition of 20% fetal calf serum (FCS) or 20% normal human serum
      (NHS), (c) 40% NHS or 40% CsATPS. Results at 96 h in (a) CsA inhibited uptake
      from 300 ng/ml, in (b) CsA inhibited [3H]thymidine uptake from 2400 ng/ml for
      cultures with FCS and 4800 ng/ml for cultures with NHS, in (c) CsATPS produced
      [3H]thymidine uptake inhibition compared with NHS. CONCLUSION: CsA alone
      inhibited [3H]thymidine incorporation in NHOb from concentrations similar to
      therapeutic concentrations. With FCS or NHS, inhibition was produced at higher
      concentrations. CsATPS inhibited at CsA concentrations lower than those of the
      two previous experiments.

PMID- 7819831
TI  - The receptor, metabolism and effects of androgen in osteoblastic MC3T3-E1 cells.
AB  - We investigated the androgen receptor (AR), metabolism and effects of androgens
      in osteoblastic MC3T3-E1 cells. AR was proved as a transcript of a 10-kb mRNA and
      as a 110-kDa protein. An immunocytochemical study showed that AR was located
      mainly in the nuclei. Specific binding of [3H]DHT was observed in both the
      nuclear and cytosol fractions. MC3T3-E1 cells possessed approximately 1190
      binding sites per cell and most of the sites (1150 sites) situated in the
      nucleus. The apparent Kd value in the nuclear fraction was 1.35 nM for [3H]DHT
      binding, and it was similar to that for [3H]testosterone. In the competition
      analysis, there was not much difference in the displacement of the [3H]DHT
      binding from AR between the addition of radioinert DHT and testosterone. In
      studies of 5 alpha-reductase activity and aromatase activity of the cells, both
      activities were lower than the respective values in classical androgen target
      tissues. Androgens stimulated the incorporation of [3H]thymidine into the cell,
      and DHT and testosterone had a similar potency on the cell proliferation. Thus,
      these results suggest testosterone itself acts mainly on the osteoblasts without
      conversion to DHT.

PMID- 7819832
TI  - 1,25-Dihydroxyvitamin D3 and osteocalcin in maternal and fetal guinea pigs.
AB  - Maternal and fetal 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and osteocalcin were
      measured in guinea pigs, to examine their potential use as animal models for
      fetal bone development and calcium homeostasis. Measurements were performed on
      days 42, 57 and 63 of gestation. Maternal serum total 1,25(OH)2D3 concentrations
      were increased only at the end of gestation (day 63). However, because the
      vitamin D binding protein (DBP) and albumin levels were decreased by 35-50% from
      day 42 onwards, the unbound 1,25(OH)2D3, calculated as the 1,25(OH)2D3/DBP molar
      ratio, was increased before day 63. Osteocalcin concentrations during gestation
      were 50-54% of levels found in nongravid animals. Fetal serum total 1,25(OH)2D3
      concentrations were 20% of those in maternal guinea pigs. Since DBP levels were
      only 9-15% of maternal levels, the unbound 1,25(OH)2D3 was consistently higher in
      fetuses, from day 42 onwards. There was a rise in total and unbound 1,25(OH)2D3
      between days 57 and 63 of fetal life. Osteocalcin concentrations were higher in
      fetal than in adult guinea pigs, and reached peak values on day 57 (1023
      micrograms/l, i.e. 4.2 times higher than in adult female guinea pigs). Fetuses of
      guinea pigs that had received a restricted food supply for 14 days (days 49-63)
      had normal 1,25(OH)2D3 concentrations, but decreased osteocalcin concentrations
      compared with normal fetuses. The data obtained in fetal guinea pigs are
      comparable with those found in human fetuses, and suggest that the guinea pig may
      be a suitable model for studies on fetal bone and mineral development.

PMID- 7819833
TI  - Whatever happened to the reform of American health policy?

PMID- 7819834
TI  - Doctors and climatic change.

PMID- 7819835
TI  - Medical informatics: the professional challenge.

PMID- 7819836
TI  - Macroglossia.

PMID- 7819838
TI  - Pressure mounts over patients with hepatitis C.

PMID- 7819837
TI  - The primary health care non-team.

PMID- 7819839
TI  - German parliament investigates HIV infections.

PMID- 7819840
TI  - Oregon's voters approve assisted suicide measure.

PMID- 7819841
TI  - Stress case paves way for damages claims.

PMID- 7819842
TI  - Debate over US Gulf war syndrome continues.

PMID- 7819843
TI  - Satisfied customers grow for NHS.

PMID- 7819844
TI  - Victims of violence flood Rio's hospitals.

PMID- 7819845
TI  - Eclampsia in the United Kingdom.
AB  - OBJECTIVES: To measure the incidence of eclampsia, establish how often it is
      preceded by signs of pre-eclampsia, document the morbidity associated with
      eclampsia, and determine the maternal case fatality rates. DESIGN: A prospective,
      descriptive study of every case of eclampsia in the United Kingdom in 1992.
      Information was collected from reviews of hospital case notes and questionnaires
      to general practitioners. SETTING: All 279 hospitals in the United Kingdom with a
      consultant obstetric unit. RESULTS: Obstetricians and midwives notified 582
      possible cases, and 383 were confirmed as eclampsia. The national incidence of
      eclampsia was 4.9/10,000 maternities (95% confidence interval 4.5 to 5.4). Most
      convulsions occurred despite antenatal care (70%) and within one week of the
      woman's last visit to a doctor or midwife (85%). Three quarters of first seizures
      occurred in hospital, of which 38% developed before both proteinuria and
      hypertension had been documented. Forty four per cent of cases occurred
      postpartum, more than a third (38%) antepartum, and the remainder (18%)
      intrapartum. Nearly one in 50 women (1.8%) died, and 35% of all women had at
      least one major complication. The rate of stillbirths and neonatal deaths was
      22.2/1000 and 34.1/1000, respectively. Preterm eclampsia occurred more commonly
      antepartum and was associated with more maternal complications and fetuses that
      were small for gestational age, as well as with higher rates of stillbirth and
      neonatal mortality. Antepartum eclampsia, which was more likely to occur preterm,
      was associated with a higher rate of maternal complications and a higher neonatal
      mortality. Both factors (gestational prematurity and antepartum occurrence)
      contributed independently to the severity of the outcome. CONCLUSION: Eclampsia
      occurs in nearly one in 2000 maternities in the United Kingdom and is associated
      with high maternal morbidity and fatality in cases. It may present unheralded by
      warning signs. Preterm and antenatal eclampsia seem to be particularly severe.

PMID- 7819846
TI  - Midwife managed delivery unit: a randomised controlled comparison with consultant
      led care.
AB  - OBJECTIVE: To examine whether intrapartum care and delivery of low risk women in
      a midwife managed delivery unit differs from that in a consultant led labour
      ward. DESIGN: Pragmatic randomised controlled trial. Subjects were randomised in
      a 2:1 ratio between the midwives unit and the labour ward. SETTING: Aberdeen
      Maternity Hospital, Grampian. SUBJECTS: 2844 low risk women, as defined by
      existing booking criteria for general practitioner units in Grampian. 1900 women
      were randomised to the midwives unit and 944 to the labour ward. MAIN OUTCOME
      MEASURES: Maternal and perinatal morbidity. RESULTS: Of the women randomised to
      the midwives unit, 647 (34%) were transferred to the labour ward antepartum, 303
      (16%) were transferred intrapartum, and 80 (4%) were lost to follow up. 870 women
      (46%) were delivered in the midwives unit. Primigravid women (255/596, 43%) were
      significantly more likely to be transferred intrapartum than multi-gravid women
      (48/577, 8%). Significant differences between the midwives unit and labour ward
      were found in monitoring, fetal distress, analgesia, mobility, and use of
      episiotomy. There were no significant differences in mode of delivery or fetal
      outcome. CONCLUSIONS: Midwife managed intrapartum care for low risk women results
      in more mobility and less intervention with no increase in neonatal morbidity.
      However, the high rate of transfer shows that antenatal criteria are unable to
      determine who will remain at low risk throughout pregnancy and labour.

PMID- 7819847
TI  - Impact of massive dose of vitamin A given to preschool children with acute
      diarrhoea on subsequent respiratory and diarrhoeal morbidity.
AB  - OBJECTIVE: To assess the impact of vitamin A supplementation on morbidity from
      acute respiratory tract infections and diarrhoea. DESIGN: Double blind randomised
      placebo controlled field trial. SETTING: An urban slum area in New Delhi, India.
      SUBJECTS: 900 children aged 12-60 months attending a local health facility for
      acute diarrhoea of less than seven days' duration randomly allocated to receive
      vitamin A 200,000 IU or placebo. MAIN OUTCOME MEASURES: Incidence and prevalence
      of acute lower respiratory tract infections and diarrhoea during the 90 days
      after termination of the enrolment diarrhoeal episode measured by twice weekly
      household surveillance. RESULTS: The incidence (relative risk 1.07; 95%
      confidence interval 0.92 to 1.26) and average number of days spent with acute
      lower respiratory tract infections were similar in the vitamin A supplementation
      and placebo groups. Among children aged 23 months or less there was a significant
      reduction in the incidence of measles (relative risk 0.06; 95% confidence
      interval 0.01 to 0.48). The incidence of diarrhoea was also similar (relative
      risk 0.95; 0.86 to 1.05) in the two groups. There was a 36% reduction in the mean
      daily prevalence of diarrhoea associated with fever in the vitamin A supplemented
      children older than 23 months. CONCLUSIONS: Results were consistent with a lack
      of impact on acute lower respiratory tract related mortality after vitamin A
      supplementation noted in other trials and a possible reduction in the severity of
      diarrhoea.

PMID- 7819848
TI  - Management of ventricular fibrillation by doctors in cardiac arrest teams.

PMID- 7819849
TI  - Ten year follow up of microprolactinoma treated by transsphenoidal surgery.

PMID- 7819850
TI  - Acute hemiparesis associated with ciprofloxacin.

PMID- 7819851
TI  - Enalapril and bullous eruptions.

PMID- 7819852
TI  - Sleep disturbance in children treated with ofloxacin.

PMID- 7819853
TI  - Prospective study of bacterial meningitis in North East Thames region, 1991-3,
      during introduction of Haemophilus influenzae vaccine.
AB  - OBJECTIVE: To describe the epidemiology of primary bacterial meningitis in the
      North East Thames region over a three year period before and during the
      introduction of the vaccine for Haemophilus influenzae type b. DESIGN: Analysis
      of information on cases of primary bacterial meningitis identified by
      microbiology laboratories in the region, with collection of case data by
      questionnaire. MAIN OUTCOME MEASURES: Annual incidence rates for types of
      meningitis according to age and ethnic group. RESULTS: The annual incidence rates
      for the three major causes of bacterial meningitis in the general population were
      1.9/100,000 for Neisseria meningitidis, 1.6/100,000 for Haemophilus influenzae
      before vaccination, and 1.0/100,000 for Streptococcus pneumoniae. Higher rates of
      H influenzae meningitis were found in Asians compared with white people
      (3.6/100,000 v 1.5/100,000, P = 0.01). As a result of the vaccine programme
      introduced in October 1992 the number of cases of H influenzae meningitis in
      children under 5 years has fallen by 87%. CONCLUSIONS: Bacterial meningitis is a
      serious problem especially in preschool children. There are differences in the
      incidence of some causes of bacterial meningitis in different ethnic groups; with
      H influenzae type b being significantly more common among black and Asian people
      than among white people. The immunisation programme for H influenzae type b in
      the North East Thames region has been successful in reducing the incidence of
      this type of meningitis in Asian and white populations. The numbers were too
      small to evaluate in the black population.

PMID- 7819854
TI  - Diagnosis and management of sinusitis.

PMID- 7819855
TI  - Use of personal medical records for research purposes.
AB  - The established practice of doctors using medical records for research purposes
      is threatened by the recent proposed guidelines from the Department of Health,
      the BMA, and the European Commission. The European Commission has proposed that
      explicit consent should be obtained from each patient before his or her medical
      records can be used; the proposals from the Department of Health and the BMA
      would require all research that needs access to personal medical records to be
      submitted to an ethics committee. We believe that these proposals would seriously
      impair an entire category of research and suggest therefore that another set of
      guidelines, proposed by a Royal College of Physicians' working group, should be
      used to modify the proposals. The guidelines of the working group encourage the
      use of medical records for research and ensure that such use can be made in a
      confidential manner without causing harm.

PMID- 7819856
TI  - WHO in crisis.
AB  - Media attention has been focused on the leadership of the World Health
      Organisation, rather than on the real factors that limit WHO's effectiveness.
      These factors relate to the organisation's structure and also to its current
      priorities, methods, and management. This article examines the objectives and
      strategy of WHO in view of financial constraints and donor countries' demands;
      WHO's stated goal of integrated primary health care; staff morale; and the
      growing dislocation between the regions and headquarters.

PMID- 7819857
TI  - Screening for carriers of cystic fibrosis. Screening before pregnancy is needed.

PMID- 7819858
TI  - Screening for carriers of cystic fibrosis. Psychological consequences are
      unclear.

PMID- 7819859
TI  - ABC of breast disease. Locally advanced breast cancer.

PMID- 7819860
TI  - Pressure sores. Knowledge of risk factors may not improve management.

PMID- 7819861
TI  - Pressure sores. Not considered a priority by medical staff.

PMID- 7819862
TI  - Pressure sores. Compare maximum and minimum pressures.

PMID- 7819863
TI  - Evening primrose oil. Does not show promise in atopic dermatitis.

PMID- 7819864
TI  - Future of inpatient adolescent psychiatric units. NHS reforms address existing
      deficiencies.

PMID- 7819865
TI  - Marginal analysis in practice.

PMID- 7819866
TI  - Diet and cancer.

PMID- 7819867
TI  - Interpreting results of observational research. P values are still useful.

PMID- 7819868
TI  - Persistent post-traumatic stress disorder.

PMID- 7819869
TI  - Generic inhalers for asthma.

PMID- 7819870
TI  - Triglyceride concentration and coronary heart disease.

PMID- 7819871
TI  - Excessive expenditure of income on treatments in developing countries.

PMID- 7819872
TI  - Protection afforded by cycle helmets.

PMID- 7819873
TI  - Vitamin K for neonates.

PMID- 7819874
TI  - Should obesity be treated? Patients with sleep apnoea should be treated.

PMID- 7819875
TI  - Resuscitation and patients' views.

PMID- 7819876
TI  - Reye's syndrome.

PMID- 7819877
TI  - What's happening to AIDS?

PMID- 7819878
TI  - The five years after qualification.

PMID- 7819879
TI  - Diagnosing pulmonary embolism.

PMID- 7819880
TI  - Botulinum toxin in the cerebral palsies.

PMID- 7819881
TI  - Follow up by telephone.

PMID- 7819882
TI  - Doctors are more miserable than ever, says report.

PMID- 7819884
TI  - Italian doctors plan protest action.

PMID- 7819883
TI  - Court upholds force feeding for mental illness.

PMID- 7819885
TI  - Canberra legalises cannabis for patients in trials.

PMID- 7819886
TI  - New inquiry launched into cot death.

PMID- 7819887
TI  - British patients demand to use cannabis.

PMID- 7819888
TI  - Judge bans hepatitis C test kits.

PMID- 7819889
TI  - Paediatrician found guilty of misconduct.

PMID- 7819890
TI  - French doctors criticise new bioethics law.

PMID- 7819891
TI  - Does symptomatic primary HIV-1 infection accelerate progression to CDC stage IV
      disease, CD4 count below 200 x 10(6)/l, AIDS, and death from AIDS?
AB  - OBJECTIVE: To investigate the prognostic significance of symptomatic primary HIV
      1 infection. DESIGN: Prospective study of homosexual men seroconverting to HIV in
      1985 and 1986. Patients were followed up at least three times yearly with
      clinical examinations and T cell subset determinations for an average of 7.2
      years. SETTING: Research project centred on attenders for treatment and screening
      for HIV at the Karolinska Institute, Stockholm. SUBJECTS: 19 patients presenting
      with a glandular-fever-like illness associated with seroconversion to HIV and 29
      asymptomatic seroconverters. MAIN OUTCOME MEASURES: Progression to Centers for
      Disease Control and Prevention stage IV disease, CD4 cell count below 200 x
      10(6)/l, AIDS, and death from AIDS. RESULTS: Symptomatic seroconverters were
      significantly more likely to develop Centers for Disease Control and Prevention
      stage IV disease (95% v 66%), CD4 cell counts below 200 x 10(6)/l (84% v 55%),
      and AIDS (58% v 28%) and die of AIDS (53% v 7%). CONCLUSION: A glandular-fever
      like illness associated with seroconversion to HIV-1 predicts accelerated
      progression to AIDS and other HIV related diseases.

PMID- 7819892
TI  - HIV disease progression in 854 women and men infected through injecting drug use
      and heterosexual sex and followed for up to nine years from seroconversion.
      Italian Seroconversion Study.
AB  - OBJECTIVE: To compare the progression of HIV-1 infection in men and women
      followed up for up to nine years after an accurately estimated date of
      seroconversion. DESIGN: Prospective observational study. SETTING: 16 HIV
      outpatient clinics across Italy. SUBJECTS: 321 women and 533 men infected with
      HIV through injecting drug use or heterosexual sex and with accurately estimated
      dates of seroconversion. MAIN OUTCOME MEASURES: Progression to severe CD4
      lymphocytopenia (CD4 lymphocyte count < 200 x 10(6)/l), development of AIDS
      defining diseases, and death from AIDS. RESULTS: Thirty two women and 67 men
      developed AIDS at Kaplan-Meier progression rates of 25% (95% confidence interval
      13.8% to 35.5%) and 23% (15.6% to 30.4%), respectively, 7 years after
      seroconversion. In a Cox proportional hazards model the relative hazard was 0.93
      (that is, a slightly lower hazard in women) before and 1.10 (0.70 to 1.72) after
      adjusting for age, HIV exposure group, and year of seroconversion. When CD4
      lymphocytopenia and death from AIDS were used as end points the results were
      similar, with adjusted relative hazards of 0.95 (0.63 to 1.42) and 0.72 (0.48 to
      1.79) respectively. In both women and men the risk of developing AIDS before the
      CD4 lymphocyte count had declined below 200 x 10(6)/l was small (3% in women, 6%
      in men). The estimated median count at which AIDS developed in women (34 x
      10(6)/l; 10 x 10(6) to 44 x 10(6)) was similar to that for men (44 x 10(6)/l; 22
      x 10(6) to 60 x 10(6)). CONCLUSION: There seems to be little evidence for
      appreciable differences in the natural course of HIV infection between men and
      women followed up from the time of seroconversion.

PMID- 7819893
TI  - National survey of hospital patients.
AB  - OBJECTIVE: To survey patients' opinions of their experiences in hospital in order
      to produce data that can help managers and doctors to identify and solve
      problems. DESIGN: Random sample of 36 NHS hospitals, stratified by size of
      hospital (number of beds), area (north, midlands, south east, south west), and
      type of hospital (teaching or non-teaching, trust or directly managed). From each
      hospital a random sample of, on average, 143 patients was interviewed at home or
      the place of discharge two to four weeks after discharge by means of a structured
      questionnaire about their treatment in hospital. SUBJECTS: 5150 randomly chosen
      NHS patients recently discharged from acute hospitals in England. Subjects had
      been patients on medical and surgical wards apart from paediatric, maternity,
      psychiatric, and geriatric wards. MAIN OUTCOME MEASURES: Patients' responses to
      direct questions about preadmission procedures, admission, communication with
      staff, physical care, tests and operations, help from staff, pain management, and
      discharge planning. Patients' responses to general questions about their degree
      of satisfaction in hospitals. RESULTS: Problems were reported by patients,
      particularly with regard to communication with staff (56% (2824/5020) had not
      been given written or printed information); pain management (33% (1042/3162) of
      those suffering pain were in pain all or most of the time); and discharge
      planning (70% (3599/5124) had not been told about warning signs and 62%
      (3177/5119) had not been told when to resume normal activities). Hospitals failed
      to reach the standards of the Patient's Charter--for example, in explaining the
      treatment proposed and giving patients the option of not taking part in student
      training. Answers to questions about patient satisfaction were, however, highly
      positive but of little use to managers. CONCLUSIONS: This survey has highlighted
      several problems with treatment in NHS hospitals. Asking patients direct
      questions about what happened rather than how satisfied they were with treatment
      can elucidate the problems that exist and so enable them to be solved.

PMID- 7819894
TI  - Choice of antidepressants: questionnaire survey of psychiatrists and general
      practitioners in two areas of Sweden.
AB  - OBJECTIVE: To identify factors that affect physicians' choice of specific
      antidepressant drugs in order to evaluate the validity of epidemiological studies
      of the risks (particularly suicide) and benefits of different compounds. DESIGN:
      Questionnaire survey of 264 psychiatrists and general practitioners in an urban
      area and a rural area of Sweden with validation of data by independent
      prescription surveys. SETTING: Urban area of greater Stockholm and rural county
      of Jamtland, Sweden. SUBJECTS: 228 physicians (86%) who answered the
      questionnaire. MAIN OUTCOME MEASURES: The drugs used as first line drugs of
      choice, as drugs of choice in particularly severe depression, and as drugs of
      choice for disorders other than depression. RESULTS: Amitriptyline was the most
      common first line drug of choice among both psychiatrists and general
      practitioners. The patterns of choice of antidepressants in the two areas
      accorded with prescribing patterns in two independent prescription surveys.
      Amitriptyline was chosen even more frequently for severe depression and
      depression with severe insomnia. Clomipramine was chosen comparatively more often
      for depression with severe anxiety. Low toxicity compounds (mainly lofepramine,
      mianserin, and moclobemide) were more often the drug of choice in depression
      associated with overt risk of suicide. Amitriptyline and clomipramine were used
      extensively for disorders other than depression (40% and 54% of prescriptions,
      compared with 13-19% for some other major antidepressants). CONCLUSION: Patient
      groups treated with different antidepressant compounds may not be comparable with
      respect to diagnoses and severity of disease. In particular, lofepramine,
      mianserin, and moclobemide, and possibly amitriptyline, seem to be chosen more
      often for patients prone to suicide.

PMID- 7819895
TI  - Impact of HIV infection on Zambian businesses.

PMID- 7819896
TI  - Epitrochlear lymph nodes as marker of HIV disease in sub-Saharan Africa.

PMID- 7819897
TI  - Interpretation of electrocardiograms by doctors.

PMID- 7819898
TI  - Provision of services for cleft lip and palate in England and Wales.

PMID- 7819899
TI  - Effect of non-attenders on the potential of a primary care programme to reduce
      cardiovascular risk in the population. Family Heart Study Group.
AB  - OBJECTIVES: To determine the feasibility of enrolling non-attenders of a
      population based cardiovascular risk reduction programme (the British family
      heart study) into a further, similar programme and to assess the effect of non
      attendance on the effectiveness of the programme. DESIGN: Follow up of non
      attenders by practice nurses, including home visits if necessary, to administer
      questionnaires and obtain physiological measurements. SETTING: Eight general
      practices across England, Scotland, and Wales. SUBJECTS: Non-attenders in a
      cardiovascular risk factor screening and intervention programme compared with
      attenders. MAIN OUTCOME MEASURES: Number of non-attenders enrolled;
      sociodemographic characteristics; personal and family history of coronary heart
      disease; cardiovascular risk factors; and total coronary risk score. RESULTS:
      Data were collected from 106 (17%) of the 608 non-attending families (99 men and
      42 women). Of the 543 non-attending families from five practices that attempted
      complete follow up, 256 had moved away or died. Only 76 were eventually enrolled
      into the study. The prevalence of coronary heart disease and a family history of
      coronary heart disease were similar among non-attenders and attenders as were the
      individual coronary risk factors studied except smoking. Women non-attenders were
      more likely to be current cigarette smokers than attenders (15/42 v 202/948, P =
      0.02). CONCLUSIONS: The intensive follow up of non-attenders resulted in real
      intervention opportunities in only a small number. Since the effect of any
      intervention in a population is reduced by non-attendance audit of preventive
      medical programmes aimed at the population should allow for the effect of non
      attenders on the overall results.

PMID- 7819900
TI  - Glomerulonephritis: diagnosis and treatment.

PMID- 7819901
TI  - Getting started as a medical manager.

PMID- 7819902
TI  - The World Health Organisation. The regions--too much power, too little effect.
AB  - WHO's regional offices make it structurally one of the most decentralised of all
      United Nations agencies. But at what cost and to what effect? This article argues
      that too often the regions give only the illusion of decentralisation while
      wresting power from WHO's governing body and prolonging the time taken for
      resources to reach the point of need.

PMID- 7819903
TI  - Eradication of Helicobacter pylori should be pivotal in managing peptic
      ulceration. Eradication largely prevents relapse.

PMID- 7819904
TI  - Eradication of Helicobacter pylori should be pivotal in managing peptic
      ulceration. Helicobacter pylori is not the causative agent.

PMID- 7819905
TI  - ABC of breast diseases. Prognostic factors.

PMID- 7819906
TI  - Care of dying patients in hospital. Patients' interests should be put before
      research.

PMID- 7819907
TI  - Detecting bilateral isodense subdural haematomas. Patient should lie supine for
      30 minutes.

PMID- 7819908
TI  - Detecting bilateral isodense subdural haematomas. Appearances in scan were
      obvious.

PMID- 7819909
TI  - New resource allocation formula. Agism by stealth.

PMID- 7819910
TI  - New resource allocation formula. Socioeconomic status does not always reflect
      health.

PMID- 7819911
TI  - Moderate drinking and loss of brain cells. Factor converting imperial to metric
      measures was wrong.

PMID- 7819912
TI  - Doctor's right to refuse to perform abortions. Antiabortion views are not
      incompatible with gynaecology.

PMID- 7819913
TI  - Doctors' right to refuse to perform abortions. Law doesn't include GPs and junior
      doctors.

PMID- 7819914
TI  - Health promotion. Target all risk factors.

PMID- 7819915
TI  - Hyperbaric oxygen in crush syndrome.

PMID- 7819916
TI  - Overdosage during patient controlled analgesia. ...and below the level of the
      patient.

PMID- 7819917
TI  - Overdosage during patient controlled analgesia. Follow manufacturers'
      instructions.

PMID- 7819918
TI  - Circadian variation in deliberate self poisoning.

PMID- 7819919
TI  - n of 1 trials.

PMID- 7819921
TI  - Matching inhalers and spacer devices.

PMID- 7819920
TI  - Managing sharps injuries.

PMID- 7819922
TI  - Postnatal sexual health.

PMID- 7819923
TI  - Payment for blood donations.

PMID- 7819924
TI  - Out of hours.

PMID- 7819925
TI  - Fire retardants, biocides, plasticisers, and sudden infant deaths.

PMID- 7819926
TI  - Internal market rules OK.

PMID- 7819927
TI  - Questioning academic integrity.

PMID- 7819929
TI  - Rwanda counts the cost of atrocities.

PMID- 7819928
TI  - Scottish death rates published with health warning.

PMID- 7819930
TI  - Back treatment needs revolution, says report.

PMID- 7819931
TI  - Judge blocks Oregon's assisted suicide measure.

PMID- 7819933
TI  - Surgeon General resigns in masturbation row.

PMID- 7819932
TI  - Sydney surgeon accused of HIV transfer.

PMID- 7819934
TI  - Heart muscle disease related to HIV infection: prognostic implications.
AB  - OBJECTIVES: To determine the natural course of heart muscle disease in patients
      infected with HIV. DESIGN: Prospective echocardiographic survey and observational
      study over four years. SETTING: Edinburgh. SUBJECTS: 296 adults infected with HIV
      (mean age 32.7 years (range 21.5 to 67.6) drawn from all the major groups at risk
      of HIV infection in Britain. MAIN OUTCOME MEASURES: Detection of myocardial
      dysfunction and time to death from index echocardiogram in serial
      echocardiography. RESULTS: Cardiac dysfunction was identified in 44 subjects
      (dilated cardiomyopathy, 13; isolated right ventricular dysfunction, 12;
      borderline left ventricular dysfunction, 19). Dilated cardiomyopathy was strongly
      associated with a CD4 cell count of < 100 x 10(6)/l, in contrast with the other
      forms of cardiac dysfunction. During the study 12/13 (92%) subjects with dilated
      cardiomyopathy, 5/12 (42%) with right ventricular dysfunction, and 8/19 (42%)
      with borderline left ventricular function died of conditions related to AIDS.
      Survival was significantly reduced in the subjects with dilated cardiomyopathy
      compared with those with normal hearts (P < 0.001). The median survival from the
      index echocardiogram was 101 days (95% confidence interval 42 to 146) for the
      subjects with cardiomyopathy compared with 472 days (383 to 560) for those with
      normal hearts and a CD4 cell count of < 20 x 10(6)/l. No significant difference
      existed in survival for subjects with borderline left or isolated right
      ventricular dysfunction. CONCLUSION: Even after adjustment for the significantly
      reduced CD4 cell count with which dilated cardiomyopathy is associated, the
      outlook for patients with HIV infection and dilated cardiomyopathy is poor.
      Isolated right and borderline left ventricular dysfunction are not associated
      with reduced CD4 cells counts and do not carry adverse prognostic implications.

PMID- 7819935
TI  - Role of glycaemic control in development of microalbuminuria in patients with
      insulin dependent diabetes.
AB  - OBJECTIVE: To ascertain which factors determine the progression from very low
      rates of albumin excretion to persistent microalbuminuria in patients with
      insulin dependent diabetes mellitus. DESIGN: A 10 year prospective study of a
      cohort of diabetic patients. SETTING: Outpatient department of the Portsmouth
      District Hospitals. SUBJECTS: 97 patients with insulin dependent diabetes
      mellitus who were initially free of microalbuminuria and hypertension. MAIN
      OUTCOME MEASURE: Urinary albumin: creatinine ratio. RESULTS: Eight of the 97
      patients had developed microalbuminuria (urinary albumin:creatinine ratio > 3
      mg/mmol in three consecutive early morning samples) by the 10 year follow up. The
      group who developed microalbuminuria had higher baseline log10 plasma glucose
      concentrations (mean (SD), 1.210 (0.122) v 0.984 (0.196) mmol/l, P < 0.001) and
      glycated haemoglobin concentrations (1.112% (0.069%) v 0.997% (0.076%), P <
      0.001) and a younger age at onset of diabetes (10.0 (5.5) v 15.6 (7.8) years, P <
      0.05). There was no difference in baseline duration of diabetes, smoking, sex,
      insulin dose, body mass index, serum creatinine concentration, or systolic,
      diastolic, or mean arterial blood pressure between the two groups. Multiple
      linear regression analysis showed that urinary albumin:creatinine ratio at 10
      years was influenced by initial albumin:creatinine ratio (P = 0.006), initial
      glycated haemoglobin concentration (P = 0.002), and duration of diabetes (P =
      0.045). Genotype for angiotensin converting enzyme was not related to the
      development of microalbuminuria nor, in a larger group of patients, the presence
      of any degree of diabetic nephropathy. CONCLUSION: In patients with insulin
      dependent diabetes mellitus the progression of minimal albuminuria and the
      development of microalbuminuria is determined primarily by poor long term
      glycaemic control. There is a weaker relation with longer duration of disease and
      younger age at onset of diabetes, but blood pressure does not seem to be
      implicated. Gene polymorphism for angiotensin converting enzyme is not linked to
      the development of microalbuminuria or established diabetic nephropathy.

PMID- 7819936
TI  - Population based survival rates for childhood cancer in Britain, 1980-91.
AB  - OBJECTIVES: To investigate the survival of children with cancer diagnosed during
      1980-91 in order to assess the impact of developments in medical care on a
      population basis. DESIGN: Retrospective cohort study. SETTING: Great Britain.
      SUBJECTS: 14973 children with cancer diagnosed during 1980-91 and included in the
      population based National Registry of Childhood Tumours. MAIN OUTCOME MEASURES:
      Actuarial survival rates. RESULTS: For all cancers combined, two year survival
      increased from 66% to 76% between 1980-2 and 1989-91, and five year survival
      increased from 57% to 65% between 1980-2 and 1986-8. Significant increases in
      survival rates occurred among children with acute lymphoblastic leukaemia, acute
      nonlymphocytic leukaemia, retinoblastoma, osteosarcoma, Ewing's sarcoma,
      rhabdomyosarcoma, and malignant gonadal germ cell tumours. No trend in survival
      was seen for children with Hodgkin's disease, central nervous system tumours,
      neuroblastoma, or Wilms's tumour. CONCLUSIONS: Nearly two thirds of children who
      have cancer diagnosed can now expect to survive at least 10 years.

PMID- 7819937
TI  - Left ventricular mass in normotensive subjects with autosomal dominant polycystic
      kidney disease.

PMID- 7819938
TI  - Do asthmatic patients correctly record home spirometry measurements?

PMID- 7819939
TI  - Pertussis immunisation of children with histories of neurological problems.

PMID- 7819940
TI  - Anisocoria associated with selective serotonin reuptake inhibitors.

PMID- 7819941
TI  - Arthralgias and omeprazole.

PMID- 7819942
TI  - Erythromycin deafness and cimetidine treatment.

PMID- 7819943
TI  - Parotitis induced by chlormethiazole.

PMID- 7819944
TI  - Organisation of primary care services outside normal working hours.
AB  - OBJECTIVE: To determine the use and organisation of out of hours services in
      primary care. DESIGN: Telephone survey. SETTING: Family health services
      authorities in England and Wales. MAIN OUTCOME MEASURES: Rate of use of out of
      hours care, methods of provision, and role of authorities. RESULTS: 12-25% of
      authorities were unable to answer one or more key questions in the survey because
      of insufficient information. The mean number of night visits made per
      unrestricted principal per 1000 patients per year was 35.3. 13 of the 19
      authorities with averages above 40 covered large towns or cities. 81 authorities
      had at least one commercial deputising service. In 46 metropolitan districts and
      one other district over 75% of general practitioners had consent to use a
      deputising service, although not all did so. Information on cooperation between
      practices was limited. 22 cooperatives were recognised by the authorities, nine
      were not officially recognised, and a further 13 were nearing institution. Only
      two cooperatives were in areas with extensive use of deputising services.
      CONCLUSION: Methods of providing out of hours care are changing, and without good
      information systems family health services authorities will not be able to
      monitor the effect on quality and cost effectiveness of care.

PMID- 7819945
TI  - Out of hours service: the Danish solution examined.
AB  - In Denmark the provision of out of hours care by general practitioners came under
      increasing pressure in the 1980s because of growing demand for services by the
      public and increasing complaints from rural doctors about their heavy workload
      and disproportionately low remuneration in comparison with urban doctors. As a
      result, the out of hours service was reformed at the start of 1992: locally
      negotiated rota systems were replaced with county based services. Each county now
      has a coordination centre, where all patients' calls are received by a team of
      doctors. The doctors may give a telephone consultation, advise the patient to
      attend one of the emergency clinics strategically placed about the county, or
      arrange for a home visit. Doctors on home visiting duty are located at bases
      throughout the county and keep in touch with the coordination centre with mobile
      telephones. Graded fees mean that doctors are encouraged to give telephone
      consultations rather than arrange for clinic consultations or home visits. The
      reforms have reduced doctors' out of hours workload and the number of home visits
      made and have proved acceptable to patients, doctors, and administrators.

PMID- 7819946
TI  - Out of hours primary care centres: characteristics of those attending and
      declining to attend.
AB  - OBJECTIVES: To study the number, demography, and clinical details of patients who
      agreed or refused to attend centralised primary care centres for out of hours
      medical care and to study the satisfaction with the service of those who
      attended. DESIGN: Data collected by telephonists and doctors. Satisfaction
      questionnaires given to patients who attended. SETTING: Five out of hours primary
      care centres in the United Kingdom. SUBJECTS: All patients contacting the
      deputising service to request medical help out of hours who were asked to attend
      a primary care centre. The study terminated when 1000 patients had agreed to
      attend (200 from each centre). 1000 patients not agreeing to attend were also
      sampled. RESULTS: The attendance rate varied from 8.9% to 52.3% in the five
      centres. The overall standardised attendance rate was 22.4%. The attendance rate
      was highest in children under 5 (465/2380, 19.5%) and fell with increasing age.
      Of the 1000 sampled non-attenders, 403 said that they had no transport and 345
      said that they were too ill to attend. Those who attended were seen by the doctor
      more quickly. There was no significant difference between the groups in the
      number who received a prescription (810 attenders v 820 non-attenders, P = 0.57)
      or who were admitted to hospital (59 v 52, P = 0.5). Satisfaction with the
      service among those who attended was very high; 95% (694/731) said that they
      would be prepared to attend under similar circumstances in the future.
      CONCLUSION: Most patients are not able or prepared to attend a central facility
      for primary care out of hours. Substantial cultural change will be necessary and
      careful consideration given to planning if such centres are to provide a major
      part of out of hours care.

PMID- 7819947
TI  - Quality standards for deputising services.

PMID- 7819948
TI  - Cardiology--II: Treatment of heart failure and atrial fibrillation and
      arrhythmias.

PMID- 7819949
TI  - WHO at country level--a little impact, no strategy.
AB  - The acid test of WHO's effect on the world's health is its impact at country
      level. Unless it has an impact there, all of its declarations, its debates at the
      World Health Assembly, its conferences, its pamphlets, its political manouvering
      in Geneva and the regions, all of these come to nothing. Working as it does
      through national governments, WHO insists that it has no role in directly
      managing or delivering health care. Judging WHO's impact in individual countries
      is therefore difficult--its approaches are largely indirect, and initiatives may
      take years to bear fruit. But from the meagre resources that WHO makes available
      at country level it is clear why its country operations are criticised as the
      weakest link in an already weak chain of influence from its headquarters in
      Geneva to the people in its member states. Poorly funded, undertrained, and with
      no clear strategy to follow, its staff at country level stand little chance of
      making an impact.

PMID- 7819950
TI  - Gagging public health doctors.

PMID- 7819951
TI  - An unfree NHS and medical press in an unfree society.

PMID- 7819952
TI  - Irritable bowel or irritable mind? Medical treatment works for those with clear
      diagnosis.

PMID- 7819953
TI  - Irritable bowel or irritable mind? Psychological treatment is essential for some.

PMID- 7819954
TI  - ABC of breast diseases. Psychological aspects.

PMID- 7819955
TI  - Effective top teams: luxury or necessity?

PMID- 7819956
TI  - Medicine's core values. Medical care does add to life expectancy.

PMID- 7819957
TI  - Medicine's core values. Profession should not have to make decisions concerning
      rationing.

PMID- 7819958
TI  - Medicine's core values. The consultation is foundation stone of medicine.

PMID- 7819959
TI  - Medicine's core values. Should include respect.

PMID- 7819960
TI  - Medicine's core values. Statement of intent needed.

PMID- 7819961
TI  - Medicine's core values. The right to speak out.

PMID- 7819962
TI  - The future of public health. Further economic growth may not improve health.

PMID- 7819963
TI  - Unanimity in the profession. Any academy should stay away from realpolitik.

PMID- 7819964
TI  - Unanimity in the profession. Don't pretend to be unanimous.

PMID- 7819965
TI  - Eradicating gonorrhoea. More is needed than just treatment.

PMID- 7819966
TI  - Eradicating gonorrhoea. No "epidemiological" treatment.

PMID- 7819967
TI  - Eradicating gonorrhoea. Open access for screening is vital.

PMID- 7819968
TI  - Initial management of suspected meningococcal infection. Parenteral
      benzylpenicillin is vital.

PMID- 7819969
TI  - Initial management of suspected meningococcal infection. Chief medical officer's
      guidelines are right.

PMID- 7819971
TI  - Mammography after treatment for breast cancer.

PMID- 7819970
TI  - Initial management of suspected meningococcal infection. On the spot treatment
      needed.

PMID- 7819972
TI  - Risk factors for breast cancer. Socioeconomic differences might be explained by
      body mass.

PMID- 7819973
TI  - Medical staffing in general hospitals.

PMID- 7819974
TI  - Purchasing vascular services.

PMID- 7819975
TI  - Rural general practitioners and out of hours cover. New scheme is ill conceived.

PMID- 7819976
TI  - Rural general practitioners and out of hours cover. The need for a humane
      contract.

PMID- 7819977
TI  - The inhumanity of medicine.

PMID- 7819978
TI  - Medical marriages.

PMID- 7819979
TI  - The rich man in his castle.

PMID- 7819980
TI  - The poor man at his gate.

PMID- 7819981
TI  - The animal kingdom bites back.

PMID- 7819982
TI  - The miracle of DICE therapy for acute stroke: fact or fictional product of
      subgroup analysis?
AB  - OBJECTIVE: To determine whether inappropriate subgroup analysis together with
      chance could change the conclusion of a systematic review of several randomised
      trials of an ineffective treatment. DESIGN: 44 randomised controlled trials of
      DICE therapy for stroke were performed (simulated by rolling different coloured
      dice; two trials per investigator). Each roll of the dice yielded the outcome
      (death or survival) for that "patient." Publication bias was also simulated. The
      results were combined in a systematic review. SETTING: Edinburgh. MAIN OUTCOME
      MEASURE: Mortality. RESULTS: The "hypothesis generating" trial suggested that
      DICE therapy provided complete protection against death from acute stroke.
      However, analysis of all the trials suggested a reduction of only 11% (SD 11) in
      the odds of death. A predefined subgroup analysis by colour of dice suggested
      that red dice therapy increased the odds by 9% (22). If the analysis excluded red
      dice trials and those of poor methodological quality the odds decreased by 22%
      (13, 2P = 0.09). Analysis of "published" trials showed a decrease of 23% (13, 2P
      = 0.07) while analysis of only those in which the trialist had become familiar
      with the intervention showed a decrease of 39% (17, 2P = 0.02). CONCLUSION: The
      early benefits of DICE therapy were not confirmed by subsequent trials. A
      plausible (but inappropriate) subset analysis of the effects of treatment led to
      the qualitatively different conclusion that DICE therapy reduced mortality,
      whereas in truth it was ineffective. Chance influences the outcome of clinical
      trials and systematic reviews of trials much more than many investigators
      realise, and its effects may lead to incorrect conclusions about the benefits of
      treatment.

PMID- 7819983
TI  - Handedness and longevity: archival study of cricketers.
AB  - OBJECTIVE: To test whether handedness is associated with a change in longevity.
      DESIGN: Archival survey. SETTING: British Isles. SUBJECTS: All first class
      cricketers born before 1961 whose bowling hand was specified (right, n = 5041;
      left, n = 1132) in a comprehensive encyclopaedia. MAIN OUTCOME MEASURES: Bowling
      hand and life span. RESULTS: Regression analysis of the 5960 players born between
      1840 and 1960 (3387 dead, 2573 alive) showed no significant relation between
      mortality and handedness (P = 0.3). Left handedness was, however, associated with
      an increased likelihood of death from unnatural causes (P = 0.03, log hazard
      0.37, 95% confidence interval 0.04 to 0.70). This effect was especially related
      to deaths during warfare (P = 0.009, log hazard 0.53, 0.13 to 0.92). CONCLUSION:
      Left handedness is not, in general, associated with an increase in mortality.

PMID- 7819984
TI  - Colour blind cricketers and snowballs.
AB  - OBJECTIVE: To determine whether colour blindness affects batting in professional
      cricketers. DESIGN: Comparison of batting averages of colour blind cricketers and
      those with normal vision. SETTING: Players on 18 first class county cricket
      teams. SUBJECTS: 280 of 306 players were tested. MAIN OUTCOME MEASURES: Results
      of Isihara colour blindness tests. RESULTS: Batting average for the colour blind
      group (12 players) was slightly lower than for players with normal vision (20.88
      v 26.31). There was no difference in the number of batsmen and bowlers affected.
      Batting averages before and after the introduction of the white ball into Sunday
      League cricket did not differ significantly. CONCLUSIONS: That batting
      performance is not significantly impaired by colour blindness suggests that to
      some extent these players are self selected. Routine testing of cricketers for
      colour blindness is not recommended.

PMID- 7819985
TI  - How sensitive are cardiac surgeons' fingers?

PMID- 7819986
TI  - Ability to distinguish whisky (uisge beatha) from brandy (cognac).
AB  - OBJECTIVE: To assess ability to distinguish between first rate malt whisky and
      brandy and between different brands of each. DESIGN: Crossover with two sessions
      of 12 blindfold tastings of two whiskies and two brandies before and after
      supper, repeated not more than seven days later. SETTING: Dundas, Ontario.
      PARTICIPANTS: 4 volunteers aged 50-68 years, all moderate drinkers of alcohol and
      members of a wine club. MAIN OUTCOME MEASURES: Proportion of samples correctly
      identified (whisky v brandy) and, of those, the proportion of brands correctly
      identified. RESULTS: Only one participant produced irrefutable statistical
      evidence (P < 0.0001) of being able to distinguish between whisky and brandy,
      correctly identifying 50/51 (98%) samples. Two participants achieved some success
      in identification (72%, P = 0.0031 and 65% P = 0.031). The fourth participant's
      responses reflected pure guesswork. Brandy was no easier to identify than whisky
      (P = 0.84). The participant who was best able to distinguish between whisky and
      brandy was also best able to identify correctly the brand of whisky (100%, P <
      0.0001). CONCLUSION: Despite the fact that not all participants completed the
      full number of tastings the results show that some participants could distinguish
      neither between malt whisky and brandy nor between different brands of whisky and
      brandy. However, the success of one participant shows that "it can be done" and
      that his whisky specific ability is acquired not innate.

PMID- 7819987
TI  - Effect of ale, garlic, and soured cream on the appetite of leeches.

PMID- 7819988
TI  - The killing season--fact or fiction?

PMID- 7819989
TI  - Crocodile bites and traditional beliefs in Korogwe District, Tanzania.
AB  - OBJECTIVES: To investigate why fatal crocodile bites are increasing in a
      Tanzanian district and the importance of traditional beliefs and superstitions in
      determining the residents' response to the crocodiles. DESIGN: Information about
      beliefs was obtained by interview of Korogwe residents. Human and crocodile
      fatality statistics were obtained from the Korogwe Department of Natural
      Resources. SETTING: Villages within Korogwe District. SUBJECTS: Population of
      Korogwe District. RESULTS: Crocodiles have been responsible for 51 deaths in the
      52 months from January 1990 to April 1994. Of these, 18 deaths occurred in the
      first four months of 1994. CONCLUSIONS: Local beliefs and superstitions about
      crocodiles include those about the taming of animals, with implications
      concerning the choice of victim and the penalties that may ensue if a crocodile
      is killed. The recent rise in human fatalities is thought to relate to increasing
      river pollution reducing the fish supply, together with a change in social mores
      at the riverside which has increased the crocodiles' displeasure. A reliable
      pumped water supply would reduce the need to draw water and bathe in the river,
      and eradication of superstition would empower the villagers in the fight against
      a common enemy.

PMID- 7819990
TI  - Come back DDT--all is forgiven.

PMID- 7819991
TI  - Tickborne melanoma?

PMID- 7819992
TI  - Squirrel bites.

PMID- 7819993
TI  - Once bitten, twice shy.

PMID- 7819994
TI  - The price of truth.

PMID- 7819995
TI  - A passage through grief--the Western Australian Rural Pregnancy Loss Team.

PMID- 7819996
TI  - The lean and slippered pantaloon.

PMID- 7819997
TI  - Sartorial eloquence: does it exist in the paediatrician-patient relationship?
AB  - OBJECTIVE: To evaluate children's and parents' perceptions of hospital doctors'
      attire. DESIGN: Questionnaire study asking children and parents to assign
      positive and negative attributes to five photographs of a male or female doctor
      dressed formally and informally. SETTING: Outpatient department, Children's
      Hospital, Birmingham. SUBJECTS: 203 consecutive child-parent pairs attending
      outpatient clinics over three months. MAIN OUTCOME MEASURES: Children's and
      parents' preferences, assessed by comparing proportions. RESULTS: 70% (286/406)
      of children and parents rated doctors' dress as important; more children rated it
      "very important" (27% (54/203) v 14% (29/203), P < 0.01, 95% confidence interval
      for difference 5% to 21%). Of the 99 children responding, 44 regarded the man in
      white coat as most competent (44% v 20% expected by chance, P < 0.01, 34% to 54%)
      and most concerned (32% v 20%, P < 0.01, 23% to 41%). Children also regarded the
      woman in white coat as most competent; however, male and female doctors in white
      coats rated lower for friendliness. Asians and regular surgical attenders
      preferred doctors in white coats. The man in polo shirt and trousers was rated as
      most friendly (40% v 20% expected by chance, P < 0.01, 30% to 50%) and most
      gentle (37% v 20%, P < 0.01, 27% to 46%). The woman in tee shirt and slacks also
      rated most friendly and gentle; however, both casually dressed doctors rated
      lower for competence. Parents preferred more casual dress but expressed
      preferences less strongly, and they poorly predicted which outfits their children
      preferred. CONCLUSIONS: Children regard formally dressed doctors as competent but
      not friendly; they regard casual dress as friendly but not competent.

PMID- 7819998
TI  - John Marshall: the making of true spectacles.
AB  - In 1693 John Marshall of London devised a novel method of grinding batches of
      identical, good quality, lenses of a specified focal length. Its commendation by
      the Royal Society led to a trade war between Marshall and rivals in the
      Worshipful Company of Spectacle Makers. Despite initial opposition the method was
      rapidly adopted by London opticians and, though much modified, it forms the
      unrecognised basis of present day practice.

PMID- 7819999
TI  - Dr Doubledose: a taste of one's own medicine.

PMID- 7820000
TI  - The earliest days of first aid.
AB  - First aid, as a profession in its own right, has a history of only 120 years. It
      evolved from the teachings of the Royal Humane Society and military surgeons, who
      saw the wisdom of training in splinting and bandaging for battlefield wounds. In
      1878 two Aberdeenshire military officers, Surgeon-Major Peter Shepherd of the
      Royal Herbert Military Hospital, Woolwich, London, and Colonel Francis Duncan
      established the concept of teaching first aid skills to civilians. This radical
      new enterprise, conducted under the auspices of the newly formed St John
      Ambulance Association, was a natural evolution from the body's philanthropic and
      ambulance transport work. Shepherd conducted the first class in the hall of the
      Presbyterian school in Woolwich using a comprehensive first aid curriculum that
      he had developed. Within months of that first class, local Woolwich civilians
      used their skills when the pleasure boat Princess Alice sank in the Thames at
      Woolwich, killing 600 people. Within a decade, the new discipline of first aid
      spread rapidly throughout the world, and by the end of the 19th century, hundreds
      of thousands of St John first aid certificates had been awarded in four
      continents. Shepherd's pioneering classes changed the world's concept of the need
      for the provision of skilled prehospital care.

PMID- 7820001
TI  - Adelaide Bartlett and the Pimlico mystery.
AB  - In 1886 Adelaide Bartlett stood trial at the Old Bailey for the murder of her
      husband, Thomas Edwin Bartlett. The court witnessed sensational evidence and the
      case left questions which remain unanswered.

PMID- 7820002
TI  - Frederick Cayley Robinson's Acts of Mercy murals at the Middlesex Hospital,
      London.

PMID- 7820003
TI  - Thank you, Mr Shaw.

PMID- 7820004
TI  - Medicine and the Gulag.
AB  - The nature of the medical treatment of prisoners in the Gulag has emerged from
      accounts published by survivors. Over a period of 70 years some doctors entrusted
      with the medical care of prisoners failed to discharge their ethical duties,
      contributing to the prisoners' neglect and suffering. The medical profession must
      carefully examine what occurred and properly assign responsibility for ethical as
      well as unethical medical acts. Understanding the history of these ominous events
      will alert doctors worldwide to the importance of medical autonomy in the support
      of imprisoned patients.

PMID- 7820005
TI  - Medicine at the centre of the nation's affairs.
AB  - The medical profession was shaped a century or so ago by the interaction of three
      forces. These were a class structure in which doctors were largely held to be
      gentlemen to whom deference was due, a society dominated by the activity of
      production (hence the label of the working class for the majority), and the
      doctrines of liberalism as the guiding star in politics. Prime Minister Gladstone
      defined his task as "opening doors and windows." The outcome was a minimum of
      government interference and control with the belief that professional self
      regulation was the way to ensure that practice matched principle. The state (the
      word was hardly ever used) was self effacing almost to the point of non
      existence. These are ghosts of the past, but it is a comparatively recent past.
      Within memory, the major domestic preoccupation of politicians of all parties was
      how, and to what ends, the working class could be absorbed into the political
      system. Health had a crucial part to play in this task, as Lloyd George and
      others saw early on. The "panel" was very much a forerunner of the NHS. Indeed,
      Bevan based part of his case in 1946 on the claim that 21 million people were
      already on the "panel," clear evidence of the degree to which society was still
      dominated by production. While speaking of Nye Bevan, we might examine his claim
      that the NHS was "pure socialism." In fact, it was rather closer to being "impure
      liberalism" in the consideration with which general practitioners and consultants
      were treated, the considerable freedom enjoyed by local administrations, and the
      low profile of government itself. That is why many remember the period as
      something of a golden age. It suited almost everyone very well.

PMID- 7820006
TI  - Whatalotwegot--the messages in drug advertisements.
AB  - Advertisers are increasingly using symbols to circumvent logical argument when
      trying to persuade people (the "targets" of the advertisement) to make choices
      that are not strictly rational. Symbols can convey covert meanings and awaken or
      exploit subconscious feelings, such as a desire for power or a fear of doing
      harm. Some of the ways in which pharmaceutical advertisements use these
      techniques are examined: advertising by contagion; adding to our worries;
      polarity of choices; teasers; idealisation. Rational prescribing should be based
      on logic, but advertisements do not depend on logical arguments for their most
      powerful effects: the advertisers may subvert us by appealing to our unconscious
      desires.

PMID- 7820007
TI  - Cross words.

PMID- 7820008
TI  - Christmas wishes.

PMID- 7820009
TI  - An audit of excuses.

PMID- 7820010
TI  - De inertia urbanorum.

PMID- 7820011
TI  - Another kind of flying doctor.

PMID- 7820012
TI  - It's not cricket.

PMID- 7820013
TI  - The patient's view.

PMID- 7820014
TI  - The Christmas "clacker".

PMID- 7820015
TI  - Chocolate bars in eye.

PMID- 7820016
TI  - Evidence of birth deformities in 16th century Kent.

PMID- 7820017
TI  - MRI of abdominal hydatid disease.
AB  - Seventy hydatid cysts in 30 patients were studied with magnetic resonance imaging
      (MRI) and computed tomography (CT); all cases were confirmed surgically. MRI
      detected all cysts when confined to solid organs, whereas small-sized cysts (< or
      = 2 cm) may be missed when located in the peritoneal cavity. Hydatid cysts of
      less than 3 cm (noncomplicated) present no specific findings of hydatid disease.
      MRI findings suggesting hydatid disease demonstrate a relatively thick hydatid
      cyst wall, daughter cysts, and germinal membrane detachment. T2-weighted images
      proved to be superior to T1- or PD-weighted images in demonstrating hydatid cyst
      wall thickness, germinal membrane detachment, and daughter cysts. In all spin
      echo sequences, the maternal cystic content presented much higher signal
      intensities than that of daughter cysts. This difference in signal intensity is
      more obvious in T2-weighted images, except in complicated, infected cases. CT
      proved to be superior to MRI in demonstrating wall calcifications.

PMID- 7820018
TI  - MRI manifestations of gastrointestinal lymphoma.
AB  - The magnetic resonance (MR) images of 11 cases of gastrointestinal lymphoma are
      presented. The findings include irregularly thickened mucosal folds, irregular
      submucosal infiltration, annular constricting lesion, exophytic tumor growth,
      mesenteric masses, and mesenteric/retroperitoneal lymphadenopathy. The tumors
      were homogeneous and intermediate in signal intensity on T1-weighted images.
      Heterogeneously increased signal intensities were noted on T2-weighted images.
      There was mild to moderate enhancement after intravenous administration of
      gadolinium dimeglumine (Gd-DTPA). The submucosal tumor infiltration might be
      outlined between the strongly GD-DTPA-enhanced mucosa and the low-intensity
      muscular layer. In one case that received tumor resection, the pathological
      examination showed destruction of most parts of the muscular layer, and the MR
      images did not disclose the low-intensity muscular zone.

PMID- 7820019
TI  - Gastric adenocarcinoma in a patient with common variable immunodeficiency.
AB  - We describe a 46-year-old man with a 20-year history of common variable
      immunodeficiency (CVID) who developed adenocarcinoma of the stomach. Although the
      mechanism is still debated, there is an increased frequency of gastric
      adenocarcinoma of the stomach in patients with CVID. Consequently, gastric
      complaints in patients with CVID should be pursued aggressively.

PMID- 7820020
TI  - Abdominal pseudotumors and simulated lymphadenopathy in MRI: differential
      features with the use of retrograde air insufflation.
AB  - In order to evaluate the contribution of retrograde air insufflation in
      decreasing the occurrence of pseudotumor appearance and mimicked lymphadenopathy
      due to nonair-distended bowel loops, we retrospectively compared two groups of
      magnetic resonance (MR) examinations. In the group receiving retrograde air
      insufflation, 10.8% (67 of 619) of images showed a tumor-like lesion due to
      nonair-distended bowel loop(s), whereas in the group not receiving air
      introduction, a tumor-like lesion was simulated in 45.6% (140 of 307) of images.
      Furthermore, a collapsed bowel loop(s) mimicking an enlarged lymph node close to
      the aorta, inferior vena cava, or bilateral iliac vessels was found in 9.5% (24
      of 252) of images of the latter group, in contrast to only 1.8% (9 of 505) of
      images of the former group. This study shows that retrograde air insufflation
      greatly reduces the occurrence of pseudotumor appearance and false impression of
      paraaortic, paracaval, or parailiac lymphadenopathy secondary to nonair-distended
      bowel loop(s).

PMID- 7820021
TI  - MR findings of hepatic cavernous hemangioma after intraarterial infusion of
      iodized oil.
AB  - Magnetic resonance (MR) imaging was performed on five tumors of three patients
      who had hepatic hemangiomas. Four tumors were given an intraarterial infusion of
      3-8 ml of iodized oil, while one tumor was not. MR images were obtained at 2.0 or
      0.5 T. A single spin echo sequence with TE of 30 ms and TR of 500 ms and a double
      echo sequence with TEs of 60 and 150 ms and TR of 2000 ms, were used to produce
      relatively T1-, T2-weighted, and heavily T2-weighted images, respectively. Follow
      up MR imaging was done 1-5 months after infusion of iodized oil. On relatively T1
      weighted images, hemangiomas showed iso- or hypointensity. On T2-weighted images,
      all tumors showed hyperintensity. However, on heavily T2-weighted images, tumors
      with iodized oil showed heterogeneous, slight hyperintensity, while tumors
      without iodized oil showed characteristic appearance of marked hyperintensity in
      hemangiomas. In hepatic cavernous hemangiomas with intraarterial infusion of
      iodized oil, familiarity with this unusual MR intensity of tumors on heavily T2
      weighted images is useful to avoid the incorrect diagnosis and to reduce the
      frequency of inappropriate hepatic resection.

PMID- 7820022
TI  - Percutaneous placement of biliary stent through T-tube tract.

PMID- 7820023
TI  - Patterns of fluid accumulation in splenic trauma: demonstration by CT.
AB  - Detection of hemoperitoneum in splenic trauma is as important as detection of the
      visceral injury itself. Observation of a consistent spectrum of fluid
      accumulation in patients with splenic trauma prompted us to investigate the
      patterns in more detail. Twenty-three computed tomographic (CT) scans in 20
      patients were evaluated with respect to presence of fluid collections in various
      peritoneal and retroperitoneal compartments. These were correlated with severity
      of injury and operative and pathologic findings. Hemoperitoneum was detected in
      the pelvis (65%), paracolic gutters (52%), left subphrenic space (48%),
      perihepatic space (48%), Morison's pouch (17%) and in the lesser sac (9%). In
      addition to free fluid, pleural fluid (39%) and retroperitoneal hematoma in the
      left anterior pararenal space (13%) were also encountered. These ancillary
      findings may help to substantiate the diagnosis of splenic trauma in equivocal
      cases, particularly when the spleen itself is obscured by artifacts. Early
      detection may reduce mortality and morbidity associated with splenic trauma.

PMID- 7820024
TI  - Radiological prediction of the depth of invasion and histologic type in early
      gastric cancer.
AB  - In cases of early gastric cancer (EGC), the depth of tumor invasion and
      histologic type are important factors in its prognosis. To predict the depth of
      invasion and histologic type by a double-contrast barium study of the stomach,
      304 consecutive patients with EGC were analyzed, comparing barium study with
      pathologic findings. We predicted the depth of invasion and histologic type
      according to the lesion size, surface pattern, and surrounding mucosal pattern.
      The depth of tumor invasion was correctly diagnosed in 65.3% (66 of 101) of
      cancers limited to the mucosal layer (m), and in 59.1% (110 of 186) of cancers
      which have invaded to the submucosal layer (sm). The histologic type was
      correctly predicted in 78.9% (56 of 71) of a differentiated adenocarcinoma, and
      73.1% (57 of 78) of an undifferentiated adenocarcinoma. Prediction of the depth
      of tumor invasion and histologic type was promising and showed good correlation
      to the pathologic findings.

PMID- 7820025
TI  - Transabdominal US staging of gastric cancer.
AB  - Penetration of gastric cancer through the wall is important because the treatment
      modality and prognosis are accordingly different. A prospective study was
      performed to assess the value of transabdominal ultrasonography in the
      differentiation of early gastric cancer limited within the mucosa and submucosa
      from advanced cancer extending into the muscle layer. Fifteen patients with early
      gastric cancer and 29 patients with advanced gastric cancer were evaluated
      preoperatively and compared with histological findings. Patients were referred
      after endoscopy and sonologists were informed of the site of the gastric lesions.
      Patients ingested 600-800 ml of boiled water and transabdominal ultrasonography
      of the gastric lesion was accomplished using a commercially available ultrasound
      equipment with 5.0 and 3.5 MHz transducers. Using the intact middle hyperechoic
      layer on sonogram as the criterion for early cancer, 10 of 15 patients with early
      gastric cancer and 27 of 29 patients with advanced gastric cancer were correctly
      diagnosed (84%). Fourteen of 15 cases with early gastric cancer showed a
      thickness of the lesion below 1.0 cm, while seven of 29 cases with advanced
      cancer showed a thickness 1.0 cm or less. We believe that transabdominal
      sonography may be a valuable method in the differentiation between early and
      advanced gastric cancer.

PMID- 7820026
TI  - Diagnosis of the invasive depth of gastric cancer.

PMID- 7820027
TI  - Angiomyolipomas of the liver in tuberous sclerosis.
AB  - Although the association of tuberous sclerosis and renal angiomyolipomas is well
      established, the occurrence of hepatic hamartomatous lesions in this disease is
      less well documented. We describe two cases of tuberous sclerosis with associated
      multiple intrahepatic angiomyolipomas, and we review the literature on this
      subject. Radiologically, angiomyolipomas can range from entirely lipomatous to
      completely solid, features which are present in our cases. A characteristic
      finding of the hepatic involvement in this disease appears to be the multiplicity
      of the lesions. We suggest that in the setting of tuberous sclerosis it is
      reasonable to assume that intrahepatic lesions represent angiomyolipomas.
      However, in nontuberous sclerosis patients with similar findings malignancy
      cannot be excluded.

PMID- 7820028
TI  - Hepatic angiomyolipoma.
AB  - The imaging and pathological appearances of a hepatic angiomyolipoma are
      presented. On ultrasound (US), the mass was well-defined and echogenic. On
      computed tomography (CT), the lesion appeared of soft tissue density with
      peripheral foci of lower density. The case illustrates the difficulty of
      detecting the fatty content of a tumor by CT when the fatty content represents
      only a small portion of the lesion. Fine-needle aspiration (FNA) cytology and
      needle biopsy did not yield diagnostic material, and the tumor was resected.

PMID- 7820029
TI  - Liver angiomyolipoma: classic and unusual presentations.
AB  - Two cases of liver angiomyolipoma (AML) are presented. The first case has the
      classical imaging findings previously reported. The second case has no fat
      content on the various imaging modalities. AML should probably be included in the
      differential diagnosis of any hypervascular lesion of the liver. Preoperative
      diagnosis with core biopsy is possible.

PMID- 7820030
TI  - Preoperative diagnosis of angiomyolipoma of the liver.
AB  - We experienced a case of surgically proven hepatic angiomyolipoma, a rare primary
      benign lipomatous tumor, which was preoperatively diagnosed by defining of its
      characteristic histologic components and benign radiologic nature with various
      imaging modalities. It was the first case that full radiologic evaluation was
      taken and internal vascular proliferation was defined by using dynamic bolus
      computed tomography (CT) prior to angiography.

PMID- 7820031
TI  - Multiple hepatorenal angiomyolipomas: diagnosis with fat suppression, gadolinium
      enhanced MRI.
AB  - Hepatic angiomyolipoma is a rare tumor which may occur as a solitary mass or as
      an associated finding with tuberous sclerosis. While computed tomography allows
      identification of the fat component of the lesion, magnetic resonance imaging
      (MRI) can provide similar information, as well as multiplanar visualization and
      further characterization of the vascular component of the lesion. MRI utilizing
      fat suppression and gadolinium enhancement may best provide all of the above
      information, as is demonstrated in this case report, thus potentially
      representing the imaging modality of choice.

PMID- 7820032
TI  - Hepatic angiomyolipoma: is fat in the liver friend or foe?

PMID- 7820033
TI  - Abdominal visceral calcification in secondary amyloidosis: CT findings.
AB  - Amyloid fibrils have an affinity for calcium, and radiographically detectable
      calcified amyloid deposits may occur in both primary and secondary amyloidosis.
      However, abdominal visceral calcification is rare. A patient with secondary
      amyloidosis due to juvenile rheumatoid arthritis is described who developed
      extensive liver, adrenal, and renal calcification shown by computed tomography.
      Adrenal calcification in amyloidosis has not been previously described.

PMID- 7820034
TI  - "Segmental" prolonged cortical nephrogram as a result of radiation damage to the
      kidneys.
AB  - We present two cases showing bilateral segmental delayed nephrograms secondary to
      radiation injury which occurred during radiation therapy for retroperitoneal
      adenopathy. The abnormal areas in the affected kidneys were not devoid of a
      nephrogram, but rather showed a persistent corticomedullary separation indicative
      of slowed perfusion. Linear margins not conforming to the normal renal lobular
      configuration were a confirmatory feature. Radiation injury should be included in
      the differential of both the asymmetric prolonged nephrogram and the "segmental"
      nephrogram.

PMID- 7820035
TI  - Nephrocalcinosis, cholelithiasis, and umbilical vein calcification in a premature
      infant.
AB  - A case of calcification of the umbilical vein in a premature infant with
      nephrocalcinosis and cholelithiasis is described. Such an association might have
      resulted from prematurity, bronchopulmonary dysplasia, umbilical vein
      catheterization, total parenteral nutrition, and furosemide therapy. Follow-up
      ultrasound examination at 9 months of age revealed spontaneous resolution of
      calcification of both the gallbladder and the umbilical vein but not of the
      kidneys.

PMID- 7820036
TI  - Regional lymphadenopathies in patients with renal calculi: analysis with
      ultrasound and MRI.
AB  - Thirty-nine patients with renal calculi were retrospectively studied with
      magnetic resonance (MR) imaging and an ultrasound (US). All patients were
      examined as part of a research project for imaging evaluation of complications of
      extracorporeal shock wave lithotripsy. Twelve of the patients showed lymph node
      enlargement in the retroperitoneal perivascular space. Adenopathies were
      visualized by MR imaging but not with US: The presence of large lymph nodes was
      associated with urinary, renal parenchymal, or stone infection. When large lymph
      nodes are found in the retroperitoneal perivascular space in patients with
      lithiasis, urinary tract infection must be assumed as the cause of these
      adenopathies.

PMID- 7820037
TI  - Idiopathic segmental thrombosis of the corpus cavernosum as a cause of partial
      priapism.
AB  - Idiopathic segmental thrombosis of the corpus cavernosum as a cause for partial
      priapism is an uncommon event. Diagnosis and treatment in the past have
      principally involved invasive methods. We present a case in which both
      conventional invasive methods and noninvasive imaging were used.

PMID- 7820039
TI  - 4th International Workshop on Hairy Cell Leukemia. Amalfi, Italy, 4-6 October
      1993. Proceedings.

PMID- 7820038
TI  - Thirty-five years in the progress of hairy cell leukemia.
AB  - Since 1958, when HCL was first recognized as a new clinical, hematologic and
      pathological entity, great progress has been made through the contributions of
      numerous investigators: The hematopathology of the hairy cell and the organs
      involved by the disease have been well established. The early controversies
      concerning the cellular origin of the hairy cell has been clarified and is now
      recognized that the hairy cell of HCL is of B-lymphocyte lineage. The position of
      the hairy cell within the spectrum of B-cell chronic lymphoproliferative
      disorders indicates that the CLL-lymphocyte is in an early stage and the hairy
      cell of HCL in a later stage in mature B-cell development. The hairy cell
      represents an activated B-CLL lymphocyte. The comparison of the immunophenotyping
      patterns of HCL and the other lymphoproliferative disorders is being clarified.
      Monoclonal antibodies raised against hairy cells or with restricted specificity
      for hairy cells, as well as other biological markets such as IL-2 and TNF, are
      being used for monitoring response to treatment and detecting minimal residual
      disease. In the last decade, major advances have been made in the treatment of
      HCL with the advent of interferon and the nucleosides. Our goal today is to
      achieve a complete response of prolonged or permanent duration. For this reason:
      Splenectomy, has only a few indications at present. After 10 years of experience
      with the interferons it is recognized that interferon induces a few complete
      responses and all patients eventually relapse. Currently the nucleosides: dCF and
      2-CdA are the first line of treatment of HCL. Both drugs have acceptable toxicity
      and induce complete remissions in the majority of patients. However, longer
      periods of observation are needed to establish the duration of response and to
      document if any patients will attain a cure by the nucleosides. In the
      continuation of the progress in achieving our goals, we definitely need: better
      parameters for the evaluation of complete response and detection of minimal
      residual disease: to search for the characteristics for prediction of response to
      therapy; long-term randomized studies between dCF and 2-CdA as an initial
      therapy, as well as randomized treatment of relapsed patients to determine the
      incidence of reinduction or cross-resistance. Meanwhile the work has to continue
      with the development of newer strategies and of new drugs, if our goal of cure of
      HCL patients is to be attained.

PMID- 7820040
TI  - Comparison of pentostatin and alpha interferon in splenectomized patients with
      active hairy cell leukemia: an intergroup study. Cancer and Leukemia Group B and
      South-West Oncology Group.
AB  - In 90 splenectomized patients with active HCL, this multi-institutional
      intergroup study showed that as compared to alpha interferon (aIF), pentostatin
      resulted in a higher incidence of response, but the difference was not
      statistically significantly. Pentostatin-induced remissions occurred
      significantly faster and such responses lasted significantly longer when compared
      with aIF induced remissions. there were no unusual toxicities observed in this
      study. This study confirms previous observations that both these agents have
      important place in therapy of hairy cell leukemia.

PMID- 7820041
TI  - Long term results with 2'deoxycoformycin in hairy cell leukemia.
AB  - We have treated 159 patients with hairy cell leukemia (HCL) with
      2'deoxycoformycin (DCF) in a phase II study that started in 1986. 151 patients
      had typical HCL and 8 HCL-variant. Ages ranged from 30 to 81 years. Most patients
      had previously received interferon-alpha, splenectomy or both and 23 had DCF as
      first line; all had active disease. In the first 40 patients DCF was given at 4
      mg/m2 weekly for 4 weeks and every 2 weeks thereafter and in the remainder every
      2 weeks until maximal response. Three patients died early on and were non
      evaluable for response. The response rates in 148 patients with typical HCL were:
      CR 74.3%, PR 22.3% and NR 3.4%. None of the HCL-variants achieved CR; 4 had PR
      and 4 NR. The median number of DCF injections to CR was 9. Lymphopenia and
      neutropenia were seen in 52% and 34%, respectively, but 72% of patients started
      treatment with low leucocyte counts. 27% had infectious complications of which 6%
      were life threatening. The disease free interval of the first 105 remitters (CR +
      PR) was 84% at 4 years with no significant difference between CR (86%) and PR
      (77%). There have been 12 relapses at a median time of 22 months (range 6-60
      months) since stopping DCF, of these, 5 had massive abdominal lymphadenopathy, a
      features seen also in 4 of the 5 primary non-responders. There were 13 deaths but
      7 were unrelated to HCL. The 5-year survival from starting DCF in 110 patients
      with typical HCL was 88% and 97% if we exclude non-HCL deaths.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7820042
TI  - Deoxycoformycin induces long-lasting remissions in hairy cell leukemia: clinical
      and biological results of two different regimens.
AB  - The use of alpha interferon (alpha IFN) and, more recently, of the purine
      analogues deoxycoformycin (dCF) and 2-chlorodeoxyadenosine (2-CdA) has
      dramatically improved the prognosis of patients affected by hairy cell leukemia
      (HCL). DCF has been shown to induce an higher and more durable response rate than
      IFN, with only moderate myelosuppression and relatively few side effects. In this
      paper, we report our experience with dCF in a series of 38 HCL patients who had
      progression of their disease after IFN therapy. Serum interleukin-1 beta (IL-1
      beta), soluble interleukin-2 receptors (sIl-2R) and Tumor Necrosis Factor alpha
      (TNF alpha) levels were also evaluated before, both during and after treatment in
      order to monitor clinical response. Two schedules of treatment were employed: 23
      patients were treated with the EORTC protocol and the following 15 with the NCI
      regimen. The overall response rate was 94.7%; no significant differences in
      response rates were observed between the two schedules. In respect to toxicity,
      we recorded nausea and in two cases a cutaneous rash. Four patients experienced
      localized herpes zoster and one had a fungal pneumonia. Median overall survival
      after therapy is 38.5 months, 55 percent of patients enrolled in the EORTC
      schedule and 77% of those who received the NCI program are currently in CCR at 3
      years. Serum IL-1 beta and sIL-2R levels significantly decreased after treatment,
      while no significant changes in serum TNF alpha levels were observed. In our
      study, dCF was confirmed as an effective agent in HCL, inducing an high response
      rate with only moderate side effects.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7820043
TI  - The Scripps Clinic experience with 2-chlorodeoxyadenosine in the treatment of
      hairy cell leukemia.
AB  - Follow-up data is now available on 144 patients with hairy cell leukemia treated
      with 2-chlorodeoxyadenosine (2-CdA) at the Scripps Clinic. Of 144 patients
      followed for a median of 14.2 months, 123 (85%) obtained complete responses, 17
      (12%) partial responses, 3 (2%) did not respond and 1 patients was unevaluable.
      So far, only 4 patients have relapsed at a median of 36 months. Fever was the
      major toxicity occurring in 43% of patients. Five patients resistant (3 patients)
      or intolerant (2 patients) to 2'-deoxycoformycin were also treated. Of these 5
      patients, 4 obtained complete responses, including 2 patients resistant to 2'
      deoxycoformycin, and 1 patient a partial response, suggesting a possible lack of
      cross-resistance between 2'-deoxycoformycin and 2-CdA in hairy-cell leukemia.
      More than 200 patients have been treated with 2-CdA worldwide with 82% obtaining
      complete remission and 12% partial remissions. Serial peripheral blood
      immunophenotypic analyses have documented the absence of circulating hairy cells.
      When bone marrow biopsies were examined using sensitive immunohistochemical
      staining techniques, residual hairy cells were detected in 25-50% of morphologic
      complete responders. Patients will need to be observed longitudinally to
      determine if this staining is predictive of relapse. A double-blind, placebo
      controlled study of pentoxifylline, a modulator of tumor necrosis factor-alpha
      and other cytokines, was performed in 2-CdA-treated hairy cell leukemia patients
      to determine whether the incidence of neutropenic fever would be reduced.
      Although pentoxifylline resulted in less febrile, hospital and antibiotic therapy
      days than placebo, only the number of days in the hospitalized patients achieved
      statistical significance. 2-CdA is emerging as the treatment of choice for hairy
      cell leukemia given the high percentage of long-lasting, complete responses that
      follow a single course of therapy.

PMID- 7820044
TI  - Hairy cell leukemia: results of 2-chlorodeoxyadenosine therapy in Jerusalem.
AB  - Since the introduction of adenosine deaminase analogues the vast majority of
      patients with Hairy cell leukemia obtain lasting complete remission. In this
      report we describe our experience with 2 CdA in 18 patients with Hairy cell
      leukemia (HCL). Ten of these had failed previous interferon therapy, 6 were
      splenectomized before and of these, 4 had also received interferon. Sixteen of
      the 18 patients receiving 2 CdA achieved complete remission (CR), 1 patient is in
      good partial response (GPR) and 1 patient has relapsed. These results are in
      keeping with those reported from other larger centers and confirm the efficacy of
      2-CdA. In this report IL-2 receptor (sIL-2R) levels were performed in most of the
      patients and found to be an accurate indicator of disease activity. Mean levels
      prior to therapy were 17200 U/ml (+/- 2500) and after successful therapy 970 U/ml
      (+/- 160). We confirm that 2-CdA treatment is the treatment of choice in HCL and
      suggest that sIL-2 levels be used as a parameter of disease activity.

PMID- 7820045
TI  - Paracrine regulation of B-cell growth in hairy cell leukemia.
AB  - There is evidence that the growth of malignant B lymphocytes e.g. hairy cells is
      regulated by cytokines. Several investigators suggested that the stimulating
      cytokines are produced by the malignant B cells indicating an autocrine growth
      regulation. Here we demonstrate that T lymphocyte clones produce soluble
      mediators which stimulate the growth of malignant B lymphocytes. The incidence of
      the growth stimulating T cell clones derived from peripheral blood is identical
      in patients with hairy cell leukemia (HCL) and healthy controls. About 50% of the
      clones stimulate the growth of hairy cells, but not the growth of purified B
      lymphocytes of healthy donors. The stimulating activity of a single clone varies
      when tested on different hairy cells. Interferon alfa but not antibodies against
      tumor necrosis factor alfa or interleukin-2 inhibit completely the growth
      stimulating activity. We propose that interferon alpha inhibits the production of
      soluble mediators produced by normal T-cells. Our results indicate that a
      paracrine growth regulation has to be considered in addition to the postulated
      autocrine loop in the growth regulation of malignant B cells.

PMID- 7820046
TI  - Molecular evaluation of clonal remission in hairy cell leukemia patients treated
      with 2-chlorodeoxyadenosine.
AB  - Several reports have documented complete and long-lasting remissions in hairy
      cell leukemia (HCL) patients after a single one-week course of 0.1 mg/kg/d of 2
      Chlorodeoxyadenosine (2-CdA) administered by intravenous infusion. In these
      studies the evaluation of the clinical response was based on physical
      examination, blood cell counts, as well as cytochemical and immunological
      detection of residual leukemic cells. Since HCL is a chronic lymphoproliferative
      disorder characterized by the expansion of monoclonal B cells, analysis of the
      configuration of the immunoglobulin gene regions represents a valuable tool
      towards a more accurate monitoring of treatment response. We hereby describe the
      molecular assessment of the neoplastic clone in six HCL patients treated with 2
      CdA; in five of them a disappearance of the rearranged bands could be documented
      in bone marrow cells aspirated between 2 and 21 months after a single course of
      continuous infusion 2-CdA. The last HCL case analyzed, revealed molecular
      persistence of the neoplastic clone. In all cases but one, the molecular
      evaluation was in agreement with the definition of clinical response based on
      conventional analysis. This study demonstrates that HCL patients treated with 2
      CdA show a high incidence of molecularly-defined complete remissions, the
      likelihood of which is much greater than for patients treated with Interferon
      alpha.

PMID- 7820047
TI  - Retreatment with 2-CdA of progressed HCL patients.
AB  - Thirty seven hairy cell leukemia (HCL) patients, 35 males and 2 females with a
      median age of 53 years, were treated with a single course of 2
      Chlorodeoxyadenosine (2-CdA) at a dose of 0.1 mg/kg daily for 7 days by
      continuous infusion. Twenty nine (78%) achieved a complete remission (CR) and 8
      (22%) a partial remission (PR); four of the latter progressed after 6, 12, 18 and
      24 months. All have been retreated with 2-CdA and 2 achieved a CR, 1 a PR and the
      last one is not yet evaluable. The overall median duration of response was 18
      months, ranging from 4 to 30 months from the end of therapy. Circulating hairy
      cells and spleen enlargement, when present, disappeared within 2 weeks after
      completing treatment. A significant neutropenia was observed in almost all
      patients mainly in those who had less than 1,000/microliters neutrophils when
      treatment was started, together with a significant lymphocytopenia which lasted
      for more than 12 months. The hemoglobin and platelet levels were marginally
      affected. Fever was observed in 14 patients; in 8 of them it was short-lived (<
      or = 48 hours) and apparently not infection-related, while in the remaining 6 it
      was attributed to infection. Clinical tolerance was very good and none of the
      patients complained of nausea, vomiting or hair loss. In conclusion, our study
      confirms the efficacy of 2-CdA in HCL, including patients who progressed after
      treatment with 2-CdA.

PMID- 7820048
TI  - Specific tissue invasion, localisation and matrix modification in hairy-cell
      leukemia.
AB  - HCs have a distinctive profile of matrix-binding integrin receptors which partly
      reflects their activated nature. HCs show differing functional responses to
      individual adhesive proteins, and these are mediated by particular integrin
      heterodimers. In particular, HCs are motile on Vitronectin (VN), and this
      motility is mediated by alpha v beta 3. HCs are immobile but actively spread on
      Fibronectin (FN) and this response is mediated by beta 1 integrins. M-CSF
      enhances the mobility (chemotaxis and chemokinesis) of HCs, and this response is
      partly mediated by alpha v beta 3. HCs synthesise and assemble fibronectin and
      this is, at least partly, the cause of the distinctive bone marrow fibrosis of
      hairy-cell leukaemia.

PMID- 7820049
TI  - Investigating hairy cell leukemia dysregulations. Looking for interferon alpha
      site of action in hairy cells.
AB  - One of the most striking characteristics of hairy cell leukemia (HCL) is its
      remarkable responsiveness to alpha-interferon (IFN-alpha) therapy. IFN-alpha is a
      multifunctional cytokine able to regulate the growth, differentiation and
      recirculation of normal and malignant B lymphocytes. These activities have been
      extensively studied in hairy cells, but none of these properties has been shown
      to fully account for IFN-alpha responsiveness. Numerous data now support the idea
      that IFN-alpha exerts its therapeutic effect both indirectly, through stimulation
      of immunocompetent cells, and directly on the hairy cells. Our approach to
      investigate the mode action of IFN-alpha in HCL has been to identify
      abnormalities which occur in these tumor cells and then to ascertain whether
      these abnormalities can be rectified by IFN-alpha treatment. A high level of free
      Ca2+ in the cytoplasm of hairy cells was identified. Increases in cytosolic Ca2+
      are believed to be a pivotal signal in regulating cell proliferation, cell
      differentiation and cell death. These high Ca2+ levels in hairy cells could be
      reduced upon treatment with IFN-alpha either in vitro or in vivo, probably acting
      by reducing Ca2+ influx into the leukemic cells. Moreover, the effect of IFN
      alpha on [Ca2+]i seems to be correlated with alteration in the pattern of
      kinase/phosphatase activities and with down-regulation of CD20 phosphorylation, a
      B cell specific phosphoprotein involved in Ca2+ influx across the plasma
      membrane.

PMID- 7820050
TI  - Expression of the IL2 receptor alpha, beta and gamma chains in hairy cell
      leukemia.
AB  - The expression of the interleukin 2 (IL2) receptor chains was investigated by
      immunofluorescence and mRNA analysis in typical and variant hairy cell leukemia
      (HCL) cases. While typical hairy cells express both the alpha and the beta
      chains, variant HCL express the IL2 receptor beta chain on the surface membrane
      but not the alpha chain. Both typical and variant HCL have mRNA transcript of the
      p64 molecule (gamma chain). In B-cell chronic lymphocytic leukemia (B-CLL), EBV
      transformed lymphoblastoid cell lines and normal B lymphocytes the expression of
      the IL2 receptor alpha and beta chains is very weak or negative. Furthermore, in
      B-CLL the IL2 receptor gamma chain shows a weaker expression compared to HCL.
      Both classic and variant HCL cases appear capable of proliferating in the
      presence of exogenous IL2, though the proliferative response of variant HCL
      appears lower than that of typical cases. Since in variant HCL the IL2 receptor
      alpha chain could not be induced by different stimuli, it appears that the CD25
      antigen may not be essential in the process of IL2-promoted growth, while p75 and
      p64 play a primary role in IL2 activation. Taken together, it is suggested that
      the expression of IL2 receptors is up- or down-regulated during the process of B
      cell lineage activation and differentiation.

PMID- 7820051
TI  - Serum interleukin 1 beta levels as a marker in hairy cell leukemia: correlation
      with disease status and sIL-2R levels.
AB  - Hairy cell leukemia (HCL) is a chronic lymphoproliferative disorder of the B cell
      lineage. In the search for specific markers with prognostic significance we
      evaluated the clinical value of IL-1 beta and sIL-2R levels in HCL patients. HCL
      patients (25) were classified according to their clinical status as "active",
      "non active" disease or partial or complete remission and response treatment. We
      found a good correlation between IL-1 beta or IL-2R levels and disease activity:
      improved clinical status or response to different therapies were associated with
      decreasing IL-1 beta or sIL-2R levels. In contrast, lack of response to therapy
      or disease progression was reflected in increases in both IL-1 beta and sIL-2R
      levels. In some patients increases of both cytokines preceded clinical symptoms.
      In conclusion our results show that IL-1 beta and s-IL-2R levels may be used as
      reliable markers for monitoring HCL activity, assessing response to treatment and
      predicting early progression of disease.

PMID- 7820052
TI  - Aberrant rearrangements within the immunoglobulin heavy chain locus in hairy cell
      leukemia.
AB  - The cell surface expression of multiple immunoglobulin heavy chain (IGH)
      isotypes, preferentially observed in hairy cell leukemia (HCL), is incompatible
      with the deletion model of IGH class switching, and alternative models involving
      RNA-splicing have been proposed. To help discriminate between these possibilities
      we have examined the configuration of the IGH locus by DNA blot in 38 cases of
      HCL. Deletion of at least one allele of C mu/C delta was seen in 14 cases (37%).
      Of 12 cases in which IgG and/or IgA were expressed, three exhibited biallelic
      deletion of C mu/C delta compatible with deletional class-switching whereas the
      remaining 9 cases retained both alleles of C mu/C delta. These data indicate that
      both DNA deletion and RNA-splicing mechanisms of class-switching may operate in
      HCL. In a further 17 cases, other unexpected abnormalities of the IGH locus
      mapping to the JH-C mu intron in one of two patterns were observed. First,
      discordance between JH and C mu in BamHI DNA digests was found in 12 cases.
      Similar patterns were observed in only 4/91 cases of B-cell chronic lymphocytic
      leukemia and 0/15 of B-cell prolymphocytic leukemia. To preclude chromosomal
      translocations involving the JH-C mu intron, rearrangements of BCL1, BCL2, BCL3,
      and MYC were sought in 23 cases but none of the cases showed oncogene
      rearrangement to the intron. Second, abnormal-sized C mu fragments arising as a
      consequence of abnormalities of the JH-C mu intron were detected in HindIII,
      BgIII, and/or Xbal digests in 10/23 cases.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7820053
TI  - Effects of lymph node stromal cells on the differentiation of a cell line
      established from an atypical prolymphocytic leukemia with phenotypes of both
      chronic lymphocytic and hairy cell leukemias.
AB  - We investigated the effects of stromal cells, obtained from lymph nodes with
      various lymphoid disorders and characterized immunocytochemically as fibroblasts,
      on the maturation of a cell line "HN" established from an atypical PLL
      (prolymphocytic leukemia) having phenotypic characteristics of both CLL (chronic
      lymphocytic leukemia) and HCL (hairy cell leukemia). Coculture with stromal
      cells, irrespective of the kind of lymphoid disease affecting the lymph node,
      induced a plasmacytoid cytology in HN cells, an increase of cIg gamma, and
      decreases of sIg gamma, CD5, CD21, HC2, and B-ly7. In contrast, coculture with
      the stromal cells produced no marked effects on hairy cells from two HCL
      patients. Similarly, coculture with stromal cell supernatant or with various
      cytokines shown to be produced by bone marrow stromal cells produced no effects
      on HN cells. We propose that lymph node stromal cells play an important role in
      the differentiation of B cells through direct contact and that HN cells will be
      useful for investigating the differentiation pathway of chronic B cell leukemia
      cells.

PMID- 7820054
TI  - The immunophenotype of hairy cell leukemia (HCL). Proposal for a scoring system
      to distinguish HCL from B-cell disorders with hairy or villous lymphocytes.
AB  - We have analysed the immunological profile of cells from 194 patients with a B
      cell disorder associated with circulating hairy or villous lymphocytes. These
      included: 69 typical HCL, 25 HCL-variant and 100 splenic lymphoma with villous
      lymphocytes (SLVL). All cases were HLA-DR+, CD19+, CD2- and most expressed Smlg
      with light chain restriction. The kappa/lambda ratios were: HCL, 1.2; SLVL, 1.5;
      and HCL-variant, 0.55. The majority were FMC7+ (89-96% of cases) and membrane
      CD22+ (73-98% of cases) and often negative with CD5 and CD23, markers
      characteristic of chronic lymphocytic leukemia. CD24 was variably expressed
      ranging from 21% of cases in HCL-variant to 60% in HCL and 89% in SLVL; CD10 and
      CD38 were positive in one third of SLVL but usually negative in HCL and HCL
      variant. Of the four markers considered typical of HCL, CD11c, CD25, HC2 and B-ly
      7, CD25 and HC2 were consistently negative in HCL-variant and a minority of SLVL
      cases expressed CD25 or HC2+ or B-ly-7+; CD11c was positive in all three
      disorders (47 to 97% of cases). Based on the most common phenotype of typical
      HCL: CD11c+, CD25+, HC2+ and B-ly-7+, we propose a scoring system which considers
      the reactivity with each of these four markers and gives 1 point if positive and
      0 points if negative. Scores range from 4 (typical of HCL) to 0 (atypical of
      HCL). 98% of HCL had high scores (3 or 4) whereas 88% of HCL-variant and 77% of
      SLVL scored 1 or 2 and no single case scored 3 or 4.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7820055
TI  - HLA typing in hairy cell leukemia.
AB  - In HCL patients some cases of familial occurrence of the disease were reported,
      without an association with a specific haplotype or HLA antigen. In a series of a
      non familial HCL patients an increase in DR11 frequency was reported. We
      performed HLA class I and class II antigens in a series of 38 consecutive HCL
      patients. An increased frequency of B17 (10/38-27%) and DR11 (22/38-57%) antigens
      compared with the normal Caucasian population was recorded. As clinical
      characteristics, no significant differences were recognized between DR11 positive
      and DR11 negative patients. In response to IFN treatment, a complete response
      (CR) was achieved in 20% of DR11 patients and in 46% of DR11 negative patients.
      In this study an increase frequency of B17 and DR11 antigens was found;
      furthermore DR11 positive patients seem to be less responsive to IFN treatment
      but a larger series of patients will have to be studied in the future in order to
      establish this observation with more certainty.

PMID- 7820056
TI  - Bone-marrow biopsy in hairy cell leukaemia (HCL) patients. Histological and
      immunohistological analysis of 46 cases treated with different therapies.
AB  - Serial bone-marrow biopsies were obtained from 46 hairy cell leukaemia (HCL)
      patients at different time intervals during the course of their disease. The
      patients were treated according to the following schemes: 14 received alpha
      lymphoblastoid interferon (alpha-IFN), 11 2-Chlorodeoxyadenosine (2CdA), and 21
      alpha-IFN first, followed by 2CdA. All the biopsies were studied by
      immunohistochemical means for the detection of minimal residual disease. The
      administration of 2CdA produced the highest reduction of both the tumor burden
      and HC index, with residual hairy cells (HCs) being undetectable at conventional
      light microscopy in most cases. In addition, 2CdA induced a higher degree of
      hypocellularity than alpha-IFN: the reduction in the amount of normal bone
      marrow, however, was less pronounced in patients who had alpha-IFN before 2CdA.
      Of 9 patients who received both alpha-IFN and 2CdA and were followed for more
      than 2 years, 3 relapsed, while the remaining 6 continued to show rare HCs 2
      years after 2CdA administration.

PMID- 7820057
TI  - Bone densitometry and histomorphometry in patients with hairy cell leukemia.
AB  - Tumor necrosis factor alpha, the cytokine that participates in the autocrine
      growth control of hairy cell leukemia has strong bone resorptive properties. This
      prompted us to look for bone involvement in HCL. Bone mineral density (BMD) was
      not decreased in 14 HCL patients who did not have radiographic evidence of bone
      destruction. Osteopenia was found in only two HCL patients with skeletal
      complications of the disease and bone pain preceded diagnosis in both cases.
      Lymphomatous infiltration of the vertebral bodies T 12/L1 was confirmed
      histologically in the female patient while bilateral necrosis of the femoral head
      preceded the diagnosis of HCL in the male patient. Histomorphometry of bone
      biopsy samples was performed in another 12, previously untreated male HCL
      patients. Trabecular bone volume was found to be reduced in 11, greatly reduced
      in 5 of them, while osteosclerosis was found in only one patient. The increase of
      trabecular bone pattern factor, a new parameter for simple quantification of
      trabecular interconnection indicated a poorly connected trabecular lattice in
      eight of these 12 patients.

PMID- 7820058
TI  - Incidence and significance of abdominal lymphadenopathy in hairy cell leukaemia.
AB  - We have investigated the incidence and significance of abdominal lymphadenopathy
      in hairy cell leukemia (HCL) by routinely CT scanning 88 patients. These included
      70 men and 18 women with a median age of 51 years (range 25-83). Abdominal CT
      scans were performed at diagnosis in 29 patients and in 59 during the course of
      the disease. Abdominal lymphadenopathy was documented in 25 patients (28%)
      overall; the incidence of abdominal lymphadenopathy was higher in relapse (56%)
      than at diagnosis (17%). All patients with lymphadenopathy had bone marrow
      disease. There is no association with age or sex but lymphadenopathy tends to be
      more common in patients with long-standing disease (median duration of disease 6
      years v one year in those without nodes) and in patients with bulky disease,
      particularly in the relapse group (splenomegaly/splenectomy in 95% vs 40%). The
      presence of abdominal nodes is also associated with relative resistance to
      treatment, with more treatment failures and fewer complete responses seen in this
      group. Most patients with lymphadenopathy had large, immature-looking hairy cells
      present in both the bone marrow and lymph nodes, when these were examined.
      Abdominal lymphadenopathy in HCL is more common than previously recognised,
      particularly in relapsed patients, and is always associated with active disease.
      The presence of large hairy cells and the relative resistance to treatment
      suggest that this phenomenon represents a form of transformation of the disease.
      Longer follow up is required to confirm this.

PMID- 7820059
TI  - Treatment of hairy cell leukemia in a decade of change. Appraisal of community
      based oncologists' opinions.
AB  - Over the past decade there have been several important new treatment options for
      hairy cell leukemia (HCL). These changes have centered around the emergence of
      new medicines starting with Alpha Interferon in the early 1980's, then
      Pentostatin, and finally in the early 90's with 2-CDA. The object of this study
      was to ascertain the treatment preference, reasons for selection, and
      ramifications of these new therapies on community-based oncologists. A
      questionnaire study was sent to 300 medical oncologists taken from the American
      Society of Clinical Oncology Membership Listings for New York, New Jersey and
      Connecticut. Questions ranging from demographic information of these physicians,
      choice of treatment for HCL reasons for their selections and the impact of these
      selections on the treatment of other diseases, as well as future research on HCL
      were asked. Seventy-eight percent of responding physicians considered 2-CDA the
      treatment of choice. Belief that this was the most effective treatment was their
      reasoning. Eighty percent felt that further research in HCL was still beneficial
      and needed. Perhaps some of this was based on the response that developments in
      the treatment of HCL had interfaced with the potential treatments of other
      diseases.

PMID- 7820060
TI  - Interferon treatment for hairy cell leukemia. An update on a cohort of 69
      patients treated from 1983 to 1986.
AB  - We report follow-up information on 69 hairy cell leukemia (HCL) patients treated
      with interferon alfa-2b (IFN) as primary treatment from 1983 to 1986. Follow-up
      through April, 1993 shows that only 14 patients have expired. Forty-seven of the
      61 patients completing the intended 12 or more months of initial IFN treatment
      were eventually considered IFN failures. Forty-three required re-treatment (41
      received a second course of IFN and 2 received pentostatin). Four patients died
      without further therapy for HCL. The median time to interferon failure was 31.3
      months. Fourteen patients are alive and have not required further treatment after
      completing their initial 12 or more months of interferon. Fifteen patients
      underwent a third course of interferon therapy at a median time after completion
      of a second course of IFN of 1.0 year. Eighteen patients were eventually treated
      with pentostatin and ten with 2-chlorodeoxyadenosine (2-CdA). Thirteen patients
      developed a second malignancy; six of these patients developed a hematologic
      malignancy between 44.6 months and 99.1 months after initiation of interferon
      therapy. We conclude that although interferon provides excellent palliation, that
      most patients will eventually require further treatment with interferon or
      chemotherapy. Future trials in HCL must be aware of the risk of second
      malignancies.

PMID- 7820061
TI  - Splenectomy following complete response to alpha interferon (IFN) therapy in
      patients with hairy cell leukemia (HCL): results of the HCL88 protocol. Italian
      Cooperative Group for the Study of Hairy Cell Leukemia (ICGHCL).
AB  - In December 1987, the Italian Cooperative Study Group for Hairy Cell Leukemia
      (ICGHCL) started a multicenter trial designed with the aim of investigating the
      possible role of splenectomy in HCL patients responding to initial treatment with
      a-IFN. Patients aged less than 65 years, diagnosed within 6 months, were included
      into the trial and treated with a-IFN (3 MU/daily) for 3 additional months after
      the achievement of CR or for a maximum of 12 months, regardless of the quality of
      the response. Patients in CR could undergo splenectomy while patients achieving
      PR after 12 months of treatment were randomized between splenectomy and
      maintenance therapy. By June, 1992, the trial closed, with 182 enrolled patients.
      Nine were subsequently determined to be not eligible while nine additional
      patients were lost at follow up. One hundred and sixty-nine patients were
      assessable for both response and survival. At the end of the induction therapy
      with a-IFN (mean time of treatment 16.9 months), 29 CR (17.7%), 100 PR (61.0%),
      26 minor responses (MR) (15.8%) and 9 (5.5%) treatment failures occurred. At the
      last follow up (March, 1993), with a mean follow up of 39 months, 5 patients had
      died and the overall survival rate at 4 years was 96%. Twelve patients underwent
      splenectomy after CR. After a mean follow up of 8.6 months, 8 relapses occurred.
      Thirty-one out of 100 were randomized between splenectomy (16 cases) and
      maintenance therapy (15 cases). The low accrual was mostly due to the rejection
      of randomization by the patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7820062
TI  - Hairy cell leukemia. An update on a cohort of 93 patients treated in a single
      institution. Effects of interferon in patients relapsing after splenectomy and in
      patients with or without maintenance treatment.
AB  - We retrospectively analysed the results of interferon alpha-2 (IFN) treatment in
      93 patients with hairy-cell leukaemia, of which 31 had previously undergone
      splenectomy. Induction treatment (3 x 10(6) U three times weekly for 12 months)
      was completed in 84 cases (90%). Peripheral hematological response was observed
      in 76 patients. Two patients had persistent splenomegaly, and response was
      observed in both cases after splenectomy. Five additional patients were
      responsive after 18-24 months of induction treatment and 1 was unresponsive. Of
      28 patients on maintenance treatment (1 x 10(6) U 3 x per week), no patient
      relapsed after a median follow-up of 30 months. The toxicity level was acceptable
      and IFN resistance was not observed. On the other hand, of 56 patients without
      maintenance treatment, 37 relapsed at a median of 19 months. Thirty of 32
      evaluable patients remained responsive to a second course of IFN. Of 19 patients
      without relapse, 11 had undergone splenectomy compared to 0/37 patients who
      relapsed (p < 0.001). In conclusion, the study shows the following, (1) IFN,
      provides excellent palliation without major toxic side effects; (2) long term
      maintenance was well tolerated and prevented peripheral haematological relapse;
      (3) lack of maintenance treatment was associated with peripheral haematological
      relapse requiring a second treatment; and (4) certain previously splenectomized
      patients may not require maintenance treatment. These long term results must be
      compared with the effectiveness and toxicity of new drugs, such as pentostatin
      and 2-chloro-deoxy-adenosine.

PMID- 7820063
TI  - Effect of magnesium on NMDA mediated toxicity and increases in [Ca2+]i and cGMP
      in cultured neocortical neurons: evidence for distinct regulation of different
      responses.
AB  - The effect of varying external concentrations of Mg2+ has been studied on NMDA
      induced toxicity, increases in the intracellular calcium concentration, [Ca2+]i,
      and cGMP production in cultured neocortical neurons. The neurotoxic potency of
      NMDA during a 5 h exposure period in 7-day-old cultures was examined in three
      different exposure media: phosphate buffered saline, PBS (137 mM NaCl, 2.7 mM
      KCl, 7.3 mM Na2HPO4, 1.5 mM KH2PO4, 0.9 mM CaCl2, 0.6 mM MgCl2; pH 7.4); PBS
      without addition of Mg2+; and Neuronal Dulbecco's Minimal Essential Medium (NDMEM
      = DMEM with a final concentration of KCl of 25.5 mM KCl; cf. Experimental
      Procedures). In the presence of Mg2+, no toxicity of NMDA was observed in PBS
      (ED50 > 1000 microM) whereas omission of Mg2+ in PBS resulted in an ED50 value
      for NMDA of 9 +/- 3 microM. Using NDMEM as the exposure medium, an intermediate
      neurotoxic potency of NMDA (ED50 = 40 +/- 5 microM) was observed. This
      intermediate value is probably due to partial attenuation of the Mg2+ block of
      the NMDA associated cation channel by the depolarizing conditions in NDMEM (with
      25.5 mM KCl). Diminishing the external Mg2+ concentration also potentiated the
      increase in [Ca2+]i after stimulation with NMDA. This potentiation was maximally
      3-fold (obtained at 300 microM NMDA), and the IC50 was 15 +/- 2 microM.
      Surprisingly, the NMDA induced production of cGMP was not sensitive to variations
      in the external Mg2+ concentration. These findings of distinct regulatory
      mechanisms of different NMDA receptor coupled responses may indicate the
      existence of several types of NMDA receptors.

PMID- 7820064
TI  - A comparison of the developing dopamine neuron phenotype in cultures of embryonic
      rat mesencephalon and hypothalamus.
AB  - Development of the dopamine (DA) neuron phenotype was monitored in cultures of
      embryonic rat mesencephalon (MES) and hypothalamus (HYP) maintained for 1 to 21
      days in vitro (DIV) in the absence of glial support cells. Cell counts following
      immunohistochemistry for tyrosine hydroxylase (TH) demonstrated that the number
      of DA neurons declined by 85% in MES cultures yet increased 5-fold in cultures of
      HYP, so that by 21 DIV equal numbers of DA neurons were present in these culture
      systems. After 21 DIV MES DA neurons exhibited a multipolar morphology, with
      numerous branching processes. HYP DA neurons were primarily fusiform in shape
      with fewer processes and process branch points. Double-label immunohistochemistry
      for TH and microtubule-associated protein 2 identified the majority of TH
      positive processes in either culture system as dendrites. Individual MES but not
      HYP DA neurons were also found to generate axons. Western analysis showed that
      between 1 and 21 DIV the concentration of TH protein increased 2-fold in MES and
      4-fold in HYP cultures. After 21 DIV the concentration of TH protein in MES
      cultures was twice that found in cultures of HYP. In the period between 1 and 21
      DIV levels of tetrahydrobiopterin (BH4) increased by 6-fold in MES and 20-fold in
      HYP cultures. After 21 DIV BH4 content was 3-fold higher in HYP than in MES
      cultures. The abundance of the mRNA encoding for GTP cyclohydrolase I, the rate
      limiting enzyme in BH4 biosynthesis, was similar in MES and HYP cultures despite
      this difference in BH4 levels. In contrast, TH mRNA was 4-fold more abundant in
      MES than in HYP cultures. Treatment of MES cultures with the DA neuron toxin 1
      methyl-4-phenylpyridinium decreased DA cell numbers, TH protein content and BH4
      levels, demonstrating that BH4 is localized primarily to DA neurons. Similar
      treatment of HYP cultures did not effect any of these parameters. Steady-state
      levels of DA and the rate of DA synthesis were both 3-fold higher in MES than in
      HYP cultures. A 95% decline in BH4 content produced by inhibiting BH4
      biosynthesis resulted in 64% and 84% declines in the rate of MES and HYP DA
      synthesis, respectively. Overall, these observations indicate that, with the
      exception of the capacity to synthesize DA, DA neurons in MES and HYP cultures
      share few common properties.

PMID- 7820065
TI  - Ganglioside GM1 reduces ethanol induced phospholipase A2 activity in synaptosomal
      preparations from mice.
AB  - The adaptation (tolerance) to chronic EtOH exposure was explained by the
      development of resistance to the disordering of the membrane phospholipids (PL).
      This phenomenon may be associated with changes in enzymes such as phospholipase
      A2 (PLA2) that govern PL metabolism. The data presented here, using the mouse
      inhalation model, supports and confirms previously reported findings that chronic
      exposure to EtOH substantially increased PLA2 activity in synaptosomal
      preparations from rat brain. We have previously reported that pretreatment with
      ganglioside GM1 reduced the intoxicating effect of EtOH in mice. The present
      study indicates that GM1 pretreatment both in vivo and in vitro reduced the EtOH
      induced activation of PLA2 in synaptosomal preparations. Thus GM1 may exert its
      neuroprotective effects by influencing deacylation/reacylation of membrane
      phospholipids.

PMID- 7820066
TI  - Structure, regional and developmental expression of rat MAP2d, a MAP2 splice
      variant encoding four microtubule-binding domains.
AB  - MAP2, a major component of microtubule polymers in neurons consists of high
      molecular weight (HMW) proteins MAP2a, MAP2b and a low molecular weight (LMW)
      MAP2c, expressed in the developing brain. These isoforms are produced from a
      single gene by alternative splicing and share identical C-termini encompassing 3
      tandem repeats, critical in microtubule binding. We describe the structure,
      regional and developmental expression of a novel MAP2 splice variant, MAP2d,
      containing an insertion whose sequence is homologous to the three and four
      repeats of MAP2 and Tau respectively. This insertion is absent from the mRNAs
      encoding HMW MAP2. MAP2d mRNAs are expressed at higher levels than MAP2c in all
      adult nervous tissues of the rat, and are found at low levels in glial cell
      cultures when compared to primary cultures of cerebellar neurons. Splicing of the
      fourth repeat in mature Tau precedes that in MAP2d during rat brain development.
      The tardive expression of a four microtubule-binding domain LMW MAP2 suggests it
      could play in extended neurites a similar role as mature Tau in axons.

PMID- 7820067
TI  - The release of acetylcholinesterase in vivo is regulated by dopaminergic systems
      in the guinea-pig substantia nigra.
AB  - Acetylcholinesterase (AChE) and dopamine are both stored and released from
      dendrites within the substantia nigra: however, it is as yet unknown whether the
      regulation of these two purported neuromodulators is in any way related. Using a
      sensitive chemiluminescent system to monitor AChE release 'on-line', the effects
      of inhibiting synthesis and storage of dopamine with alpha-methyl-p-tyrosine
      (AMPT: 250 mg/kg, i.p.) and reserpine (6 mg/kg, i.p.), respectively, have been
      studied. Both these agents significantly reduced nigral tissue dopamine levels by
      decreases of 83% and 63%, respectively; however, only AMPT had a significant
      effect in vivo on the spontaneous release of AChE compared to conscious control
      animals (66% decrease). Co-application of both AMPT and reserpine resulted in a
      significant decrease in the tissue dopamine content (95%) and in spontaneous
      release of AChE compared to conscious control guinea-pigs (72%); however, these
      effects were not significantly different from when AMPT was employed alone.
      Application of potassium ions (60 mM) or veratridine (100 microM) both evoked
      release of AChE in control animals: however, when expressed as a percentage of
      basal levels, this increase in release was not influenced by drug treatment or
      state of consciousness. These results suggest that de novo dopamine synthesis may
      at least in part, have an influential effect on release (and possibly storage) of
      AChE in the substantia nigra.

PMID- 7820068
TI  - Presynaptic modulation by dopamine and GABA opens a potassium channel in rat
      cortical, striatal and hippocampal synaptosomes via eicosanoids.
AB  - Using a K(+)-sensitive electrode in synaptosomal preparations, the presynaptic
      modulating effect of dopamine and GABA in opening a K+ channel was investigated.
      In cortical, striatal and hippocampal synaptosomes dopamine D1 and D2 agonists
      and a GABAB agonist promoted the efflux of K+ in all three preparations. The
      effect was blocked by the cyclooxygenase inhibitor, indomethacin suggesting that
      eicosanoids act as second messengers in these systems. The inference in these
      studies is that dopamine and GABA hyperpolarize presynaptic terminals thereby
      reducing Ca2+ influx and thus inhibiting the evoked release of transmitters.

PMID- 7820069
TI  - Characterization of peptidylglycine alpha-amidating monooxygenase in bovine
      hypothalamus.
AB  - In many peptide hormones and neuropeptides, the carboxyl-terminal alpha-amide
      structure is essential in eliciting their biological activity. In the present
      study, an enzymatic activity capable of converting 4-dimethylaminoazobenzene-4'
      sulfonyl-Gly-L-Phe-Gly(Dabsyl-Gly-Phe -Gly) to 4-dimethylaminoazo-benzene-4'
      sulfonyl-Gly-L-Phe-NH2(Dabsyl- Gly-Phe-NH2) was investigated in bovine
      hypothalamus. The concentrations of copper ion and ascorbic acid required for
      maximal enzyme activity were 16 microM and 2 mM, respectively. Amidating activity
      showed a pH profile with two pH optima at acidic pH (around 6.0) and neutral pH
      (around 7.5). Kinetic studies with the enzyme obtained from bovine hypothalamus
      demonstrated two distinct Km and Vmax values. The first Km and Vmax values were
      142.9 microM and 22.2 pmol/microgram/h and the second Km and Vmax values were
      22.7 microM and 4.44 pmol/microgram/h, respectively. Two molecular forms of
      amidating activity were identified by size-exclusion chromatography and the
      molecular weight of the two enzymes were estimated to be 49 kDa and 69 kDa.

PMID- 7820070
TI  - Irreversible blockade of D2 dopamine receptors by fluphenazine-N-mustard
      increases D2 dopamine receptor mRNA and proenkephalin mRNA and decreases D1
      dopamine receptor mRNA and mu and delta opioid receptors in rat striatum.
AB  - The consequences of irreversibly-inhibiting D2 dopaminergic receptors on the
      expression of D1 and D2 dopamine receptor mRNAs and proenkephalin mRNA and on the
      levels of mu- and delta-opioid receptors in rat striatum were studied following
      single or repeated administration of the irreversibly-acting D2 dopamine receptor
      antagonist, fluphenazine-N-mustard (FNM). The density of dopamine and opioid
      receptors was determined by receptor autoradiography and the levels of the mRNA
      for the D1 and D2 dopamine receptors and proenkephalin were measured by in situ
      hybridization histochemistry. Repeated treatment of rats with FNM for 6 days
      produced more than 80% inhibition of D2 dopamine receptors but less than 25%
      inhibition of D1 dopamine receptors. Repeated treatment with FNM also resulted in
      statistically significant increases in D2 dopamine receptor mRNA but decreases in
      D1 dopamine receptor mRNA. In contrast, acute treatment with FNM for 3 h had no
      significant effects on D1 or D2 dopamine receptor mRNAs in striatum. An
      examination of the effects of FNM on the opioid system showed that repeated
      treatment with FNM for 6 days produced more than a 2-fold increase in the
      expression of proenkephalin mRNA in striatum. This was accompanied by significant
      decreases in mu- and delta-opioid receptors in striatum, mainly by reducing the
      size of the patch compartment of striatum. Acute treatment with FNM for 3 h
      produced small increases in proenkephalin mRNA and mu-opioid receptors in
      striatum but had no significant effects on delta-opioid receptors. These results
      suggest that persistent inhibition of D2 dopamine receptors differentially
      regulates the expression of D1 and D2 dopamine receptor mRNA in striatum, and
      that the magnitude, duration and interval of inhibiting dopaminergic transmission
      may be important factors in regulating dopamine receptor mRNA expression. These
      results also suggest that D2 dopamine antagonists indirectly down-regulate opioid
      receptors by increasing the expression of proenkephalin mRNA, thereby increasing
      enkephalin which, in turn, decreases opioid receptors in striatum.

PMID- 7820071
TI  - Interaction of protein kinases A and C in their effects on the proenkephalin gene
      in astroglial cells.
AB  - In several cell types, the expression of the proenkephalin (PEnk) gene is
      enhanced after activation of protein kinase A. In the present study, astroglial
      cells cultured from rat cortex were used to investigate whether protein kinases A
      and C can act in a synergistic manner on the endogenous proenkephalin gene. The
      activator of protein kinase C tetradecanoylphorbolacetate (0.001-1 microM)
      increased the level of proenkephalin-mRNA in a concentration dependent manner.
      When used together with the phosphodiesterase inhibitor Rolipram (1 microM), the
      effect of tetradecanoylphorbolacetate (0.01 microM) was potentiated. 8
      Bromoadenosine 3',5'-cyclic monophosphate (0.01-1 mM) also enhanced the
      expression of the proenkephalin gene. When used together with
      tetradecanoylphorbolacetate (0.01 and 0.1 microM), respectively, both agents had
      additive effects. Inhibition of protein synthesis with cycloheximide (35 microM)
      significantly changed the effects of both agents. While the effect of 8Br.cAMP (1
      mM) on PEnk-mRNA was enhanced, that of tetradecanoylphorbolacetate (0.1 microM)
      was abolished. The results provide evidence for a synergistic effect of protein
      kinase A and C on the expression of the proenkephalin gene in astroglial cells.
      However, the protein kinases seem to act via different transcription factors on
      the expression of the proenkephalin gene.

PMID- 7820072
TI  - Recovery of central noradrenergic neurons one year after the administration of
      the neurotoxin DSP4.
AB  - The long-term effects of the systemic administration of DSP4 (N-(2-chloroethyl)N
      ethyl-2-bromobenzylamine hydrochloride), a selective noradrenergic neurotoxin, on
      the endogenous levels of monoamines and their metabolites and on alpha- and beta
      adrenoceptors in selected brain regions of the rat were examined. After 7 days,
      DSP4 caused a marked reduction (about 80%) of endogenous noradrenaline levels in
      locus coeruleus-innervated regions. At 90, 240 and 300 days after DSP4 injection,
      a partial and gradual recovery (50%, 41% and 25% of control values, respectively)
      of the noradrenaline cortical levels was evident. One year after DSP4
      administration, brain regional noradrenaline stores were almost completely
      recovered. No changes in 5-hydroxytryptamine levels were observed in the three
      time intervals, but a mild decrease in cortical and hippocampal 5
      hydroxyindolacetic acid levels was found 7 days after DSP4 injection. Following
      the profound noradrenaline depletion seen at 7 days, the cerebral cortical
      density of alpha 1-, alpha 2- and beta-adrenoceptors was significantly increased.
      Assessment of adrenergic receptors in cerebral cortex at 365 days after DSP4
      injection, indicated that alpha 1- and alpha 2-adrenoceptor densities did not
      differ from control values; however, the density of beta-adrenoceptors remained
      increased. No changes were observed in the affinities of the three types of
      adrenoceptors studied. These results indicate that after a selective
      noradrenergic denervation induced by DSP4, there is a slow and gradual recovery
      of noradrenaline stores and of alpha 1- and alpha 2-adrenoceptor populations,
      suggesting a possible regrowth and/or collateral sprouting of noradrenergic
      terminals.

PMID- 7820073
TI  - [A model of ionic osmotic homeostasis in cells upon cooling].

PMID- 7820074
TI  - [Hereditary hyperproduction of free radicals. Induction of carcinogenesis].

PMID- 7820075
TI  - [Symbiotic relationships in the complex carrier-pathogen system].

PMID- 7820076
TI  - [Risk of the action of solar ultraviolet radiation on human skin].

PMID- 7820077
TI  - [Detection of free DNA in eukaryotic cell nuclei].

PMID- 7820078
TI  - [Fractionation of comuton oxidase from rat liver].

PMID- 7820079
TI  - [Stable suppression of transcription of human papillomavirus type 18 (HPV 18) E6
      and E7 genes in transformed rat fibroblasts: use of an antisense oligonucleotide
      to the E7 gene].

PMID- 7820080
TI  - [The mechanism of toxic action of cadmium. Suppression of mitochondrial
      respiration by an organic cadmium complex].

PMID- 7820081
TI  - [Identification of a GC-element in the promotor of the murine L32 ribosomal
      protein L32 gene and the 3'-terminal region of the human apolipoprotein A-I gene,
      capable of binding with murine and human cells in vitro].

PMID- 7820082
TI  - [Epidermal growth factor stimulates repair of gamma-irradiated single-stranded
      DNA breaks in HeLa cells predominantly into nontranscribed DNA].

PMID- 7820083
TI  - [Features of EEG in 6-12 year old girls with various dermatoglyphic patterns].

PMID- 7820084
TI  - [The taxonomic status of Lasiopodomys genus voles by histochemical indicators of
      specific skin glands].

PMID- 7820085
TI  - [Amplification of genes from the mdr family in rodent cells resistant to ethidium
      bromide].

PMID- 7820086
TI  - [Selective assessment of anthropogenic risk in inhabited points of the Gomel
      region].

PMID- 7820087
TI  - [Dynamics of biological availability of (137)Cs in the soil-plant system after
      the accident at Chernobyl].

PMID- 7820088
TI  - [The effect of carnosine and carcinine on platelet function].

PMID- 7820090
TI  - [Functional asymmetry of the frontal neocortex and emotions].

PMID- 7820089
TI  - [Solid-phase synthesis of uracil-containing polyamide analogs of oligonucleotides
      (PAO) and their interaction with complementary sequences].

PMID- 7820091
TI  - [Dynamics and mechanisms of measuring the functional reserve of the heart
      ventricle in experimental renal arterial hypertension].

PMID- 7820092
TI  - [Characteristics of cytotoxic proteins secreted by natural killer cells from the
      spleens of nude mice].

PMID- 7820093
TI  - [Genetic archaeology: a new approach to studying the genetic history of the
      population].

PMID- 7820094
TI  - [Interhemisphere relationship of EEG during dominant hunger in man (coherence
      analysis)].

PMID- 7820095
TI  - [Pain sensitivity of trout and analgesia caused by intranasally administered
      dermorphin].

PMID- 7820096
TI  - [Evolution of the migratory process in roe deer].

PMID- 7820097
TI  - Involvement of membrane-bound transglutaminase in the invagination of transferrin
      into rat reticulocyte plasma membrane.
AB  - We demonstrated the invagination of transferrin into reticulocyte plasma membrane
      to learn whether membrane-bound transglutaminase (TGase, a Ca(2+)-dependent
      enzyme) is involved in this invagination. The invagination was assessed by acid
      resistance assay and antibody-inaccessibility assay. The invagination was blocked
      in the absence of ATP. [14C]Putrescine, a substrate for TGase, was incorporated
      into the membrane during the invagination. This incorporation was decreased in
      the absence of ATP or transferrin and was completely blocked in the presence of
      monodansylcadaverine or EGTA. The TGase inhibitor and EGTA also decreased the
      invagination. In the sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      (SDS-PAGE) analysis, the labeling of 43 kDa membrane protein with [14C]putrescine
      and the increase in aggregation of proteins were observed in a transferrin-, ATP-
      and Ca(2+)-dependent manner. These results provide the first evidence for
      modification of protein by TGase accompanying the invagination of transferrin
      into the membrane, and suggest that membrane-bound TGase is involved in the
      invagination step of endocytosis.

PMID- 7820098
TI  - Isolation and characterization of an alicyclic amine N-sulfotransferase from
      female rat liver.
AB  - An alicyclic amine N-sulfotransferase sulfonating 4-phenyl-1,2,3,6
      tetrahydropyridine (PTHP) was purified from female rat liver cytosol and showed a
      homogenous band with a molecular weight of 30500 on sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE). The enzyme, designated NST-1,
      catalyzed sulfonation not only of the alicyclic amine but also
      dehydroepiandrosterone, a typical substrate of hydroxysteroid sulfotransferase
      (STs), but had little sulfonating activity towards 2-naphthol, a typical
      substrate of aryl STs. The N-terminal amino acid sequence for the first 24
      residues had a high homology with those of rat liver hydroxysteroid STs.
      Therefore, it is suggested that NST-1 is classified as a member of the
      hydroxysteroid ST. Immunoblot analysis of male and female rat liver cytosol,
      carried out by using rabbit antisera raised against NST-1, indicated that the
      female cytosol contained a higher level of the enzyme than that of male. The
      marked sex difference in the expression level of NST-1 was in good accordance
      with the previous demonstration that female rat liver cytosol catalyzed
      sulfonation of PTHP to a greater extent than that of male.

PMID- 7820099
TI  - Anti-ulcer effects of lactic acid bacteria and their cell wall polysaccharides.
AB  - The anti-ulcer effects of bifidobacteria, lactobacilli and streptococci were
      examined using the acetic acid-induced gastric ulcer and ethanol-induced erosion
      models in rats. Bifidobacterium breve YIT4014 and 4043, and Bifidobacterium
      bifidum YIT4007 were administered orally, and anti-ulcer effects were confirmed
      for not only these organisms but also their polysaccharide fractions (PSFs). The
      major component of these anti-ulcer polysaccharides was rhamnose. In particular,
      polysaccharides in which the rhamnose content exceeded 60% were more effective in
      healing gastric ulcers. After administration of the PSF from B. bifidum YIT4007,
      the levels of epidermal growth factor and basic fibroblast growth factor
      increased in gastric tissues. Similar results were observed for the culture
      supernatant of gastric epithelial cells cultured with PSF. Furthermore, the
      production of 6-ketoprostaglandin F1 alpha by macrophages was also enhanced by
      PSF. These results indicated that these bacteria and their polysaccharides
      induced host repair and protective systems in the gastric ulcer model.

PMID- 7820100
TI  - Enzymatic sulfation of glycosides and their corresponding aglycones by
      arylsulfate sulfotransferase from a human intestinal bacterium.
AB  - A novel type of arylsulfate sulfotransferase (ASST) from a predominant human
      intestinal bacterium catalyzes the stoichiometric transfer of a sulfate group
      from phenolic sulfate esters to phenols. We clarified that polyphenols were
      better substrates of this enzyme than the corresponding glycosides. Additionally,
      a coumarin derivative, esculetin, was sulfated by ASST at the 6-position to give
      6-monosulfate. Therefore, ASST is more useful for the preparation of sulfated
      polyphenols at their specific hydroxyl groups and would play an important role in
      the metabolism of phenolic compounds in vegetable food and traditional medicines.

PMID- 7820101
TI  - Binding of a catechol derivative of denopamine (T-0509) and N-tert
      butylnoradrenaline (Colterol) to beta 1- and beta 2-adrenoceptors.
AB  - The affinities for beta-adrenoceptors, the subtype-selectivity and the agonistic
      effectiveness of T-0509 (a catechol derivative of denopamine) and colterol (N
      tert-butylnoradrenaline; Col) were compared with those of other beta-agonists
      using a binding assay method. Specific binding of [3H]dihydroalprenolol (3H-DHA)
      to guinea pig left ventricular and lung membranes was saturable, and Scatchard
      and Hill analyses suggested that 3H-DHA bound to both membranes with a single
      population of binding sites with no binding site cooperativity. Addition of 5'
      guanylylimidodiphosphate (GppNHp, 30 microM) led to a rightward shift of the 3H
      DHA binding displacement curves of T-0509 and Col in both membranes, and the
      degree of shift was similar to that of full agonists such as isoproterenol (Iso),
      adrenaline (Adr) and noradrenaline (NA). Both T-0509 and Col were thus considered
      to be full agonists at both beta 1- and beta 2-adrenoceptors, respectively,
      unlike denopamine and procaterol. T-0509 and Col showed considerably high
      affinity for both beta 1- and beta 2-adrenoceptors, and T-0509, like denopamine,
      was as selective for the beta 1-subtype as NA (4.5-fold compared with Iso as a
      non-selective agonist), whereas Col was more selective for the beta 2-subtype
      than Adr (4.5-fold compared with Iso).

PMID- 7820102
TI  - Antifertility activity of Striga orobanchioides.
AB  - Four successive solvent extracts of the whole plant Striga orobanchioides have
      been screened for antifertility activity in albino rats. Of these the ethanolic
      extract was found to be most effective in causing significant anti-implantation
      activity. The antifertility activity was reversible on withdrawal of treatment
      with the extract. The ethanolic extract at 200 mg/kg showed estrogenic activity.
      Histological studies of the uterus were carried out to confirm this estrogenic
      activity.

PMID- 7820103
TI  - Nephrotoxicity induced by adenine and its analogs: relationship between structure
      and renal injury.
AB  - Twenty-four adenine analogs were administered to mice and the relationship
      between the structure of analogs and the occurrence of renal injury was examined.
      Plasma urea nitrogen (UN) and creatinine levels were measured 24 h after oral
      administration of analogs. Both levels increased in the adenine-, 8-azaadenine-,
      isoguanine-, or 6-dimethyl aminopurine (6-DMAP)-administered group, but did not
      increase in the other analog groups. From light microscopy, the damages of
      tubuli, mainly of proximal tubuli, were observed in the kidneys of these four
      groups. The common property of these compounds is the strong basicity of nitrogen
      which binds the 6-position of the purine ring. Furthermore, UN and creatinine
      increased time-dependently with intravenous administration of isoguanine. When
      adenine was intravenously administered, UN slightly increased at 1 h, but
      creatinine was unchanged. No changes were observed in the 6-DMAP- or 8-azaadenine
      administered group. The basicity of nitrogen which binds to the 6-position of the
      purine ring is thus considered to be related to the occurrence of renal injury
      with oral administration, and isoguanine has high affinity with the kidney.

PMID- 7820104
TI  - 4-acylaminophenol derivatives as novel lipoxygenase inhibitors: synthesis and
      inhibitory effect on 5-lipoxygenase and leukotriene B4 production.
AB  - Structure-activity relationships in the inhibitory effects of 4-acylaminophenol
      derivatives on the 5-lipoxygenase (5-LOX) from RBL-1 cells and leukotriene B4
      (LTB4) production by guinea pig neutrophils were studied. When the N-acyl group
      was n-octanoyl or 2-thiophenecarbonyl and the size of the two ortho substituents
      of phenol was varied, the substituents bulkier than isopropyl, i.e., 2,6-di-tert
      butyl and 2,6-dicyclohexyl, substantially weakened the inhibitory activity in
      both enzymatic and cellular systems. Among the 2,6-dimethyl derivatives with an
      acyl group of various carbon-chain lengths (C1-13), those with a n-alkyl chain of
      C5 to C12 showed similarly potent inhibitory activities toward 5-LOX with an IC50
      ranging from 0.27 to 0.66 microM; in contrast, maximal inhibitory activities
      toward LTB4 production were observed in a narrower range of the serial compounds:
      i.e., those with a n-hexyl, n-heptyl, or n-octyl chain on the carbonyl carbon
      formed by far the most inhibitory group of the series and the inhibitory activity
      sharply decreased on either side of the chain length. Nearly all the active
      compounds also inhibited cyclooxygenase (COX), but the IC50 values for COX
      inhibition were more than ten times higher than the corresponding IC50 values for
      5-LOX inhibition in most cases, indicating that the acylaminophenols are
      relatively selective 5-LOX inhibitors.

PMID- 7820105
TI  - TA-2005, a novel, long-acting, and selective beta 2-adrenoceptor agonist:
      characterization of its in vivo bronchodilating action in guinea pigs and cats in
      comparison with other beta 2-agonists.
AB  - Relaxant effects of the beta 2-selective adrenoceptor agonist TA-2005 on
      bronchoconstriction in the anesthetized guinea pig and cat were evaluated in
      comparison with other known beta 2-adrenoceptor agonists. The ED50 values of
      intravenously administered TA-2005, procaterol, formoterol, isoproterenol,
      salbutamol, and salmeterol to inhibit the histamine-induced bronchoconstriction
      of the guinea pigs were 0.024, 0.053, 0.056, 0.099, 0.23, and 2.00 micrograms/kg,
      respectively, and those in serotonin-challenged cats were 0.019, 0.037, 0.039,
      0.042, 0.13, and 0.52 micrograms/kg, respectively, in the same increasing order.
      When guinea pigs were passively sensitized with anti-ovalbumin antiserum, the
      ED50 values of TA-2005, formoterol, procaterol, and isoproterenol to inhibit the
      antigen-induced bronchoconstriction were 0.09, 0.30, 0.65, and 7.0 micrograms/kg,
      i.v., respectively, while those of TA-2005, procaterol, formoterol, and
      salbutamol in actively sensitized animals were 0.24, 0.25, 1.40, and 23.0
      micrograms/kg. When TA-2005 was administered by inhalation to guinea pigs or by
      the intraduodenal route to cats, it exhibited a long-lasting inhibitory effect
      comparable or superior to the effects of salmeterol and formoterol. These data
      indicate that, among the known beta 2-adrenoceptor agonists examined, TA-2005
      exerts the most potent bronchodilating effects with a long duration of action in
      vivo, and its potency ratios to the other reference drugs were greater in antigen
      than spasmogen-induced bronchoconstriction models.

PMID- 7820106
TI  - The monoamine content of the brain in the neurofilament-deficient quail, (the
      Quiver quail).
AB  - Changes in neurotransmission are known to take place in a variety of conditions,
      such as Parkinson's disease. A neurofilament-deficient mutant of the Japanese
      quail, named the Quiver quail, exhibits generalized quivering as a clinical sign.
      The content of monoamines (noradrenaline (NA), dopamine and 5-hydroxytryptamine)
      and the uptake and release of L-[3H]NA were measured in brain of this bird. In
      Quiver, the NA content in neostriatum and thalamus, and the 5-hydroxytryptamine
      content in neostriatum, paleostriatum and thalamus were significantly increased,
      in comparison with the normal quail. The dopamine content and L-[3H]NA uptake and
      release in the Quiver mutant were similar to those in normal quail.

PMID- 7820107
TI  - Physical dependence produced by dihydroetorphine in mice.
AB  - Using various administration schedules, the physical dependence produced by
      dihydroetorphine (DHE) was compared with that of morphine in mice. Physical
      dependence, evaluated by naloxone-precipitated withdrawal signs, did not develop
      following daily treatment with DHE (10, 20, 100 and 1000 micrograms/kg, i.p. or
      30, 100 and 1000 ng/mouse, i.c.v.) for 6 d. However, 5 repeated injections of DHE
      (10 micrograms/kg, i.p.) at 1 or 2 h intervals did produce physical dependence
      and the dependent state disappeared after 2 h. Accordingly, it was demonstrated
      that a sufficient degree of antinociceptive activity needed to be maintained,
      longer than several hours, for the development of physical dependence on DHE and
      that the duration of the dependent state was very short. In the single dose
      suppression test, a single dose of DHE completely suppressed the natural
      withdrawal signs that appeared following abstinence in morphine-dependent animals
      without reappearance of significant withdrawal signs, indicating the suitability
      of DHE as a substitute for morphine. The characteristic properties of DHE, the
      extremely potent antinociceptive effect and minimal dependence, indicate the
      separation of the antinociceptive effect from dependence, and suggest that it may
      be possible to develop a novel drug which may be safely used in clinical
      situations.

PMID- 7820108
TI  - Fibrin-specific fibrinolysis induced by recombinant staphylokinase.
AB  - We compared the thrombolytic properties of recombinant staphylokinase (SAK) with
      those of streptokinase (SK), a tissue-type plasminogen activator (t-PA) and a
      urokinase-type plasminogen activator (u-PA) in the jugular vein thrombosis model
      in the rabbit in vivo and a circulating human plasma system in vitro. 50%
      thrombolysis was observed at 360 min after intravenous infusion into rabbits of
      150 micrograms/kg of SAK or 500 micrograms/kg of t-PA, respectively. And the
      fibrinogen level in the blood was not affected by either agent. 50% clot lysis in
      vitro was observed at 120 min with 1.8 micrograms/ml of SAK, 22.1 micrograms/ml
      of SK, 2.1 micrograms/ml of t-PA, or 4.7 micrograms/ml of u-PA, respectively. All
      the plasminogen activators with the exception of SAK decreased the residual
      fibrinogen level in the circulating plasma at their moderate concentration for
      clot lysis. SAK had less influence on the plasminogen and alpha 2-plasmin
      inhibitor (alpha 2-antiplasmin) levels than the other plasminogen activators.
      These findings suggest that SAK is a potent fibrin-specific thrombolytic agent.

PMID- 7820109
TI  - Generation of active oxygens, cell deformation and membrane potential changes
      upon UV-B irradiation in human blood cells.
AB  - The generation of peroxides (presumably hydrogen peroxide) by UV-B irradiation of
      human blood cells was detected. Non-fluorescent dihydrorhodamine 123 (DHR) is
      oxidized to fluorescent rhodamine 123 (R123) by H2O2 or peroxides with a
      stoichiometry of 1:1 in the presence of exogeneous peroxidase, and the
      fluorescence of R123 within the cells was measured using flow-cytometry. UV
      irradiation gave rise to changes in the cellular volume and the membrane
      potential, whose extent and direction were dependent on the type of blood cells.
      The production of peroxides (H2O2) in polymorphonuclear leukocytes is the largest
      among blood cells at the lower dose (< 0.1 J/cm2), and the production decreases
      with an increase in the dose, while the production in platelets is the smallest
      at the lower dose, but above 0.4 J/cm2 it increases suddenly so that at the
      higher dose (1.2 J/cm2) it amounts to 3.3 x 10(-16) mol/cell. For monocytes and
      lymphocytes, the production increases gradually with the increase in the dose.

PMID- 7820110
TI  - Anti-inflammatory and immunosuppressive effects of 1,6-anhydro-3,4-dideoxy-2
      furfuryl-beta-D-threo-3-enopyranose (MT2221), a novel anhydro-enopyranose
      derivative, on experimental animal models.
AB  - The anti-inflammatory effects of 1,6-anhydro-3,4-dideoxy-2-furfuryl-beta-D-threo
      3-enopyranose (MT2221) were investigated using animal models and compared with
      the effects of dexamethasone (DEX) and cyclosporin A (CYA). MT2221 inhibited
      carrageenan-induced acute inflammation and adjuvant arthritis in rats, as well as
      the delayed-type hypersensitive response and collagen-induced arthritis (CIA) in
      mice. However, it seemed that this compound was more effective against murine CIA
      than upon the other inflammation models. The MT2221 mode of action differed from
      those of conventional non-steroidal anti-inflammatory drugs (NSAIDs) and disease
      modifying anti-rheumatic drugs (DMARDs). All of these drugs are effective against
      acute inflammation or adjuvant arthritis models, but not against murine CIA. DEX
      and CYA did inhibit murine CIA, but in other animal models, their mode of action
      differed from that of MT2221. Moreover, allograft transplantation in mice showed
      that MT2221 slightly prolonged the allograft survival time. These results suggest
      that MT2221 has not only anti-inflammatory but also immunosuppressive effects
      based upon a novel mechanism of action that is different from NSAIDs, DMARDs, DEX
      and CYA.

PMID- 7820111
TI  - Accelerative effect of shikonin, alkannin and acetylshikonin on the proliferation
      of granulation tissue in rats.
AB  - The present study was carried out to compare the accelerative effect of shikonin
      (R-type), alkannin (S-type), and acetylshikonin on the proliferation of
      granulation tissue in rats, and to elucidate the correlation between the potency
      of the effect and their optical activity. Koushikon mainly contained the R-type
      of acetylshikonin, and Nanshikon mainly contained the S-type of acetylshikonin.
      Each compound produced a dose-dependent acceleration of the cotton pellet-induced
      granuloma formation. In comparing identical doses of shikonin, alkannin and
      acetylshikonin, the potency of their accelerative effects on the proliferation of
      granulation tissue was about the same. This result suggests that their absolute
      configurations (R-type or S-type) and their acetylation on the hydroxy group of
      the sidechain of shikonin or alkannin may not be important in producing the
      effect.

PMID- 7820112
TI  - Effects of ascorbic acid on iproniazid-induced hepatitis in phenobarbital-treated
      rats.
AB  - The effects of ascorbic acid (AA) on hepatic injury induced by iproniazid (IPN)
      in phenobarbital-treated rats were investigated by the evaluation of hepatic
      function using the clearance of aminopyrine (AM). Either IPN or
      isopropylhydrazine (IP-Hy), a potent toxic metabolite of IPN, were administered
      as a pretreatment to rats with or without AA. After i.v. injection of AM, the
      blood concentration of AM was determined by capillary gas chromatography by
      isotope dilution analysis using deuterium-labeled AM (AM-d9) as the internal
      standard. The kinetic parameters of AM, Vd, kel and total body clearance, were
      estimated from the time course of blood concentration. Pretreatment with IPN with
      AA led to a marked increase in the kel and in the clearance compared with
      pretreatment using IPN alone. A significant increase in the kel and the clearance
      was also found in the case of combined pretreatment using IP-Hy with AA. The
      effects of AA on the hepatic injury induced by IPN were studied according to its
      histological aspects. In the specimens obtained following the administration of
      IPN or IP-Hy with AA, the degree of cell necrosis was remarkably lowed both
      quantitatively and qualitatively. The present results clearly demonstrate that AA
      was effective in reducing IPN-induced hepatitis.

PMID- 7820113
TI  - Kinetic analysis of neuromuscular blockade. I. Relationship between twitch
      depression and stimulation frequency after d-tubocurarine administration.
AB  - The degree of twitch depression induced by nondepolarizing neuromuscular blocking
      drugs is known to be dependent on the stimulation frequency employed. Train-of
      four (TOF) stimulations with different frequencies (0.67, 1.33 and 2.0 Hz) were
      delivered to a sciatic nerve of a rat and series of four twitch heights of a
      tibialis anterior muscle were measured after d-tubocurarine (d-TC)
      administration. With a decrease of stimulus interval, twitch heights were
      intensely depressed. We hypothesized that the oservations are due to the changes
      of released amount of neuromuscular transmitter, acetylcholine, dependent on
      stimulus interval, and a pharmacokinetic/pharmacodynamic model based on the
      hypothesis was proposed. The model allowed simultaneous fitting of the twitch
      height depression after d-TC administration. It also could give a rationale to
      the fact that TOF stimulation at 2.0 Hz is a more sensitive monitoring method of
      neuromuscular function than single twitch stimulation (0.1-0.2 Hz).

PMID- 7820114
TI  - Kinetic analysis of neuromuscular blockade. II. Train-of-four fade induced by d
      tubocurarine and alpha-bungarotoxin.
AB  - The degree of train-of-four (TOF) fade, i.e., the reduction of the fourth to the
      first twitch height in a train, induced by d-tubocurarine (d-TC) and alpha
      bungarotoxin (alpha-BX) was investigated. The fade induced by d-TC was pronounced
      in comparison with that by alpha-BX, and the difference was analyzed using a
      kinetic model. Based on the assumptions: (1) Acetylcholine (ACh) binds to the
      nicotinic receptor and evokes twitch response. (2) The amount of released ACh is
      dependent on stimulus interval. (3) d-TC interacts competitively with the
      receptor. (4) alpha-BX interacts irreversibly with the receptor. It was suggested
      that the fade by d-TC and alpha-BX can be explained by the difference of the
      receptor occupancy by ACh which was caused by different interaction mechanisms of
      the two muscle relaxants with receptors.

PMID- 7820115
TI  - Percutaneous absorption of physiologically active peptides, ebiratide and
      elcatonin, in rats.
AB  - This study was designed to evaluate the percutaneous absorption of
      physiologically active peptides, ebiratide (a behaviorally potent
      adrenocorticotropic analog) and elcatonin (a hypocalcemic peptide) in an attempt
      to develop an efficient transdermal therapeutic system for the treatment of
      diseases. The [125I]ebiratide penetration through rat skin from gel formulations
      could be described fairly well by a zero-order kinetic profile. Skin penetration
      was the greatest when EDTA, n-octyl-beta-D-thioglucoside (OTG, 1.5%) and
      taurocholate (1.0%) were combined in a gel formulation. The order of flux was:
      EDTA, OTG and taurocholate (formulation 3) > OTG and taurocholate (formulation 2)
      > glucosyl-beta-cyclodextrin and OTG (formulation 4). When the transdermal
      systems of [125I]ebiratide prepared using a corresponding gel formulation were
      applied to rat abdomen, the plasma levels of radioactivity after formulations 3
      and 2 were much higher than those after formulation 1 without enhancers, and the
      radioactivity was observed in the brain, although in a very small quantity. The
      hypocalcemic effect of elcatonin was measured in vivo after application of the
      transdermal systems. The plasma calcium levels decreased comparatively rapidly
      and low levels were maintained for a long period, indicating the effectively
      percutaneous absorption of elcatonin. Formulation 7 containing D-limonen and
      taurocholate as enhancers and/or inhibitors showed much higher hypocalcemic
      effect than two other formulations combined with laurocapram or N,N-diethyl-m
      toluamide, consequently giving the highest pharmacological availability (8.7 +/-
      1.0%). These results clearly demonstrated that the peptides were effectively
      absorbed through rat skin in the presence of enhancers.

PMID- 7820116
TI  - Enhancement of the anti-tumor activity of recombinant interleukin-2 (rIL-2) by
      immunocomplexing with an F(ab')2 fragment of murine monoclonal antibody against
      rIL-2.
AB  - We have investigated the biological properties of an immune complex composed of
      recombinant interleukin-2 (rIL-2) and an F(ab')2 fragment of a monoclonal
      antibody against rIL-2 in mice for the induction of killer cells and anti-tumor
      activity, as well as the pharmacokinetic properties of the immune complex
      injected subcutaneously into mice. The immune complex demonstrated sustained
      serum rIL-2 levels, with a 2.4-times longer "mean-residence-time" than free rIL
      2. A more significant portion of rIL-2 was detected in lymph nodes after the
      subcutaneous injection of the immune complex than with rIL-2 alone. Splenic
      lymphocytes from mice given the immune complex showed higher killer cell activity
      against YAC-1 and P815 cells than those from mice given rIL-2 alone. The immune
      complex also exerted a more significant anti-tumor effect in a dose-dependent
      manner in Meth-A fibrosarcoma-bearing mice than dit rIL-2 alone.

PMID- 7820117
TI  - Anti-diabetic activity present in the fruit body of Grifola frondosa (Maitake).
      I.
AB  - The fruit body of Grifola frondosa (maitake), Basidiomycetes was confirmed to
      contain substances with anti-diabetic activity. When 1 g/d of powdered fruit body
      of maitake was given orally to a genetically diabetic mouse (KK-Ay), blood
      glucose reduction was observed, in contrast to the control group in which the
      blood glucose increased with ageing. Moreover, levels of insulin and triglyceride
      in plasma demonstrated a change similar to blood glucose with feeding of maitake.
      Ether-ethanol-soluble (ES) and hot water-soluble (WS) fractions were prepared
      from the fruit body and their hypoglycemic activity was examined. Blood glucose
      lowering activity was found when ES-fraction or WS-50% ethanol float (X) fraction
      was administered orally, but other WS-fractions were inactive. These results
      suggest that the anti-diabetic activity was present not only in the ES-fraction
      consisting of lipid but also in the X-fraction of peptidoglycan (sugar:protein =
      65:35).

PMID- 7820118
TI  - Adaptive response to low doses of gamma-ray in Chinese hamster cells: determined
      by cell survival and DNA synthesis.
AB  - This study was undertaken to examine the adaptive response in Chinese hamster V79
      cells using the cell survival (colony formation assay) and DNA synthesis
      ([3H]thymidine incorporation) as endpoints. When V79 cells were preirradiated
      with an adapting dose (0.05 Gy), their survival after irradiation with the
      challenging dose (4 Gy) was about 120% of the control without such
      preirradiation. Following irradiation with the challenging dose, the DNA
      synthesis of the preirradiated cells was less reduced than those without it. The
      adaptive responses were considered to be associated with the signal transduction
      via protein kinase C from the results that this response was not observed when
      the cells were preirradiated with the adapting dose in the presence of protein
      kinase C inhibitor, H-7.

PMID- 7820119
TI  - Specific binding of 12-O-tetradecanoylphorbol-13-acetate to histone H1.
AB  - 12-O-Tetradecanoylphorbol-13-acetate (TPA) binds specifically to histone H1
      prepared from HeLa cells and to calf histone H1 with dissociation constants of
      4.3 x 10(-7) and 9.3 x 10(-7) M, respectively. The TPA-binding to histone H1 was
      confirmed immunologically using a monoclonal antibody directed against an
      evolutionally conserved epitope of histone H1. This binding would influence DNA
      structure and the basal level of transcription, and may, in turn, account for the
      cell growth-regulatory activity of TPA.

PMID- 7820120
TI  - Proportionality of protease activities in malignant cells to their metastatic
      potentials.
AB  - It has been suggested that the activities of type IV collagenase and/or
      ectopeptidases possessed by malignant cells are related to their metastatic
      potentials. In the present study, we examined the activities of three
      aminopeptidases, two serine proteases, as well as type IV collagenase, in three
      kinds of cell lines of malignant cells. The activities of the aminopeptidases and
      serine proteases, rather than of type IV collagenase, were found to be
      proportionate to the metastatic potentials of those cell lines. Such activities
      of aminopeptidases were effectively suppressed by the addition of low molecular
      weight inhibitors.

PMID- 7820121
TI  - Age-dependent decrease in platelet aggregation in rats.
AB  - The degree of platelet aggregation induced by ADP and collagen was examined in
      platelet-rich plasma from 7- to 90-week-old rats. The aggregation induced by ADP
      was unchanged at 90 weeks. Collagen-induced aggregation decreased remarkably at
      60 and 90 weeks. Therefore, collagen-induced platelet activation is highly age
      dependent, with rats of advanced age showing a lower response than younger rats.

PMID- 7820122
TI  - Comparison of displacemental potencies of terazosin enantiomers for alpha 1
      adrenoceptor subtypes.
AB  - The present study was designed to assess displacemental potencies of terazosin
      and its isomers for alpha 1 High and alpha 1 Low adrenoceptor subtypes in rat
      brain, heart, bovine prostate and canine aorta using a radioligand binding assay
      method. Although no significant difference in pKi values of each terazosin isomer
      for alpha 1 High in canine aorta and rat brain were observed, the displacemental
      potency of (S-)terazosin for those in rat heart and bovine prostate was stronger
      than that of (R+)isomer (p < 0.01). On the other hand, only in alpha 1 Low
      subtypes of bovine prostate was stronger displacemental potency of (S-)terazosin
      than (R+)isomer (p < 0.05) observed. Thus, these results imply that there is a
      different affinity between (S-)terazosin and (R+)isomer on the alpha 1 High in
      bovine prostate and rat heart and alpha 1 Low in bovine prostate.

PMID- 7820123
TI  - Anti-inflammatory effect of 22-oxa-1 alpha,25-dihydroxyvitamin D3 on carrageenin
      induced inflammation in rats.
AB  - The anti-inflammatory effect of 22-oxa-1 alpha,25-dihydroxyvitamin D3 [22-oxa-1
      alpha,25(OH)2D3], an analogue of the active form of vitamin D3, was studied
      regarding carrageenin-induced inflammation in rats. In the early phase of the
      inflammation, the formation of granulation tissue and the weight of exudate were
      significantly suppressed by both oral and local administrations of 22-oxa-1
      alpha,25(OH)2D3 daily for 4 d (day 0-3) after carrageenin injection, though the
      local injection of 22-oxa-1 alpha,25(OH)2D3 (7 and 10 micrograms/kg) into the
      carrageenin-air-pouch was much more effective than the oral administration of the
      compound (20 micrograms/kg). Similarly, oral and local administrations of 22-oxa
      1 alpha,25(OH)2D3 from day 4 to 7 significantly suppressed the increase in
      exudate and the proliferation of granulation tissue in the late phase of
      carrageenin-induced inflammation in rats. The results suggest that 22-oxa-1
      alpha,25(OH)2D3 has an anti-inflammatory activity on both the acute and
      proliferative phases of inflammation in rats.

PMID- 7820124
TI  - Effects of kamikihito, a traditional Chinese medicine, on neurotransmitter
      receptor binding in the aged rat brain determined by in vitro autoradiography:
      changes in dopamine D1 and serotonin 5-HT2A receptor binding.
AB  - Using in vitro autoradiography, we investigated the effects of Kamikihito (KKT),
      a traditional Chinese medicine, on specific [3H]SCH23390 binding to dopamine D1
      receptors and [3H]ketanserine binding to serotonin 5-HT2A receptors in the rat
      brain. Specific binding of both compounds was affected by aging. Long-term
      administration of KKT resulted in decreases in [3H]SCH23390 binding to the cortex
      and hippocampus in aged rats, and in decreases in [3H]ketanserine binding to the
      caudate/putamen in young rats. These results suggest that the changes in dopamine
      Di and serotonin 5-HT2A receptor binding may be involved in the central effects
      of KKT.

PMID- 7820125
TI  - Nasal absorption of zidovudine and its transport to cerebrospinal fluid in rats.
AB  - The nasal absorption of zidovudine (AZT) and its subsequent transport to
      cerebrospinal fluid (CSF) was examined in rats. Both rapid absorption and a high
      CSF concentration were observed after the nasal application. Plasma and CSF
      concentrations of AZT increased when probenecid was coadministered with AZT.
      Thus, this nasal coadministration of AZT and probenecid could be useful for the
      treatment of AIDS patients with neuropathies.

PMID- 7820126
TI  - Evaluation of a pharmaceutical preparation of 2-[4-(p-fluorobenzoyl)-piperidin-1
      yl]-2'-acetonaphthone hydrochloride with enhanced dissolution rate.
AB  - A granule of 2-[4-(p-fluorobenzoyl)-piperidin-1-yl]-2'-acetonaphthone
      hydrochloride (E2001) with an enhanced dissolution rate (preparation A) prepared
      by a method previously reported (T. Tokumura, T. Tanaka, Yakuzaigaku, accepted)
      was evaluated by the dissolution test and its bioavailability in beagle dogs was
      determined. The dissolution rate of E2001 from preparation A at pH 6.0-6.8 was
      increased significantly in comparison with that from preparation B (a physical
      mixture of the same formula). There was no significant difference in Cmax, area
      under the concentration-time curve (AUC0-6 h), or Tmax between preparations A and
      B when a dose equivalent to 20 mg of E2001 was administered to the beagle dogs.
      However, a significant difference was observed between the AUC0-6 h values after
      oral administration of the two preparations with NaHCO3. These findings suggest
      that the bioavailability of E2001 from the oral administration preparation A will
      be higher than that of preparation B.

PMID- 7820127
TI  - Skin penetration enhancement of acyclovir by prodrug-enhancer combination.
AB  - The effectiveness of prodrug-enhancer combination in skin penetration enhancement
      was studied using acyclovir and its lipophilic prodrug, acyclovir butyrate, with
      octanol/water partition coefficient of 0.0123 and 0.402, respectively. In the in
      vitro diffusion experiment with rat skin, the total amount of acyclovir appearing
      in the receptor phase after administration of the aqueous suspension of acyclovir
      butyrate was smaller than that obtained after administration of acyclovir, but
      their permeability coefficients were almost equal. An enhancer, 1
      geranylazacycloheptan-2-one (GACH) did not show a large penetration enhancement
      of acyclovir (3.37-fold) but demonstrated extensive enhancement effect on the
      prodrug (12.3-fold). Most of the prodrug appeared in the form of acyclovir in the
      receptor phase without GACH, but the appearance ratio of acyclovir to total flux
      decreased with an increase in pretreatment doses of GACH.

PMID- 7820128
TI  - Biopolymers from marine invertebrates. XIV. Antifungal property of Dolabellanin
      A, a putative self-defense molecule of the sea hare, Dolabella auricularia.
AB  - Dolabellanin A (DAA), the antineoplastic and antibacterial glycoprotein purified
      from the albumen gland of Dolabella auricularia, showed an antifungal activity.
      DAA suppressed fungal growth completely at a concentration of over 2
      micrograms/ml, and the colony forming ability of the fungus was significantly
      decreased after contact with DAA. These results indicate that DAA is an
      antifungal protein and its mode of antifungal activity is fungicidal.

PMID- 7820129
TI  - Teleocidins and benzolactams inhibit cell killing by human immunodeficiency virus
      type 1 (HIV-1).
AB  - Teleocidin B-4 and structurally related synthetic benzolactams were found to be
      potent inhibitors of cell killing by HIV-1. One of the benzolactams, (-)-BL-V8
      310, showed a high selectivity index.

PMID- 7820130
TI  - Simultaneous determination of oxidized and reduced coenzyme Q and alpha
      tocopherol in biological samples by high performance liquid chromatography with
      platinum catalyst reduction and electrochemical detection.
AB  - A convenient and sensitive high performance liquid chromatographic method with
      post-column platinum catalyst reduction and electrochemical detection was applied
      to the simultaneous determination of oxidized and reduced coenzyme Q (CoQ and
      CoQH2) and alpha-tocopherol (alpha-TP) in human and rat samples. After the
      separation of oxidized and reduced CoQ homologues (CoQ8-CoQ10 and CoQ8H2-CoQ10H2)
      and alpha-TP on a reversed-phase column, oxidized CoQ homologues were reduced on
      a platinum catalyst reduction column, and then all the reduced forms were
      quantified with an electrochemical detector operated in the oxidation mode (+ 0.6
      V vs. Ag/AgCl). The order of elution was alpha-TP, CoQ8H2, CoQ9H2, CoQ8, CoQ10H2,
      CoQ9, and CoQ10 and all were well separated within 13 min. The detection limits
      at a signal-to-noise ratio of 3 were 20 pg for alpha-TP, 70 pg for CoQ8 and
      CoQ8H2, and 100 pg for CoQ9, CoQ9H2, CoQ10 and CoQ10H2. Quantitative recoveries
      (93-102%) from serum and tissues were obtained for all the analytes studied. This
      method was applied satisfactorily to the simultaneous determination of CoQ, CoQH2
      and alpha-TP in biological materials.

PMID- 7820131
TI  - [Value and clinical indications of measurements of bone density using X-ray dual
      photon absorptiometry. Report of the Comite Scientifique du Groupe dr Recherche
      et d'Information sur les Osteoporoses (GRIO)].

PMID- 7820132
TI  - The origin of synaptic neuroplasticity: crucial molecules or a dynamical cascade?
AB  - What is neuroplasticity and what are its origins? These questions have been the
      subject of intense theoretical and experimental research in the neurosciences for
      decades. Basically, the term neuroplasticity refers to the ability of neurons to
      alter some functional property in response to alterations in input. Traditional
      definitions, however, are often imprecise and restricted to particular 'model'
      neural systems. In the present article we will consider several of the most
      widely studied models of synaptic-level neuroplasticity including alterations in
      response properties of two types of invertebrate sensory neurons, long-term
      potentiation (LTP) in mammalian hippocampus and cortex, and ocular dominance
      shifts in cat visual cortex. While many other forms of neuroplasticity have been
      studied, these examples typify the diversity of the subject, as well as
      illustrate our contention that no unitary model of the phenomena is possible for
      all conditions. This last point is of particular importance for the mammalian
      literature, since many hypotheses concerning the mechanism(s) underlying the
      initiation of neuroplasticity have proposed a single crucial molecular element as
      the primary causal agent. A closer examination of these various hypotheses, in
      concert to several examples from the invertebrate literature, leads, however, to
      the conclusion that synaptic neuroplasticity must arise from a series of inter
      related molecular events of a particular form, a cascade, in which individual
      elements may differ radically from system to system. We next provide an overview
      of our studies of age-dependent regulation of excitatory and inhibitory
      ionotropic neurotransmitter receptor populations in cortex in response to agonist
      and depolarizing stimulation. We provide evidence that such regulation for
      ionotropic receptors is under the control of ionically driven receptor kinase and
      phosphatase activity which is also age-dependent in function. These data provide
      the basis for a cascade model of receptor regulation. Based on this qualitative
      model, we describe a quantitative computer simulation of certain age-dependent
      stages in the receptor regulatory cascade which may interact to produce LTP-like
      effects. While such a model is not exclusive, it nevertheless provides a
      demonstration that elements in the proposed cascade may comprise the necessary
      and sufficient conditions for some forms of neuroplasticity. We also propose some
      of the principles underlying our model as a means of unifying much of the diverse
      phenomenology reported in the literature. Finally, we make a series of explicit
      predictions which are testable with current experimental techniques.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7820133
TI  - The behavioral neurobiology of learning and memory: a conceptual reorientation.
AB  - Research on the neurobiology of learning and memory has been guided by two major
      theories: (i) memory as a psychological process and (ii) memory as a change in
      synaptic neural connectivity. It is not widely recognised that not only are these
      theories different but, moreover, they are fundamentally incompatible. Confusion
      concerning basic concepts in the learning and memory field in mammals has lead to
      the creation of an extensive but often inconclusive experimental literature.
      However, one important conclusion suggested by recent work in this field is that
      experience-dependent changes in neural connectivity occur in many different brain
      systems. Particular brain structures, such as the hippocampus, do not play any
      uniquely important role in experience-dependent behavior. Research in learning
      and memory can be best pursued on the basis of biological studies of animal
      behavior and a cellular approach to brain function.

PMID- 7820134
TI  - The pedunculopontine tegmental nucleus: a role in cognitive processes?
AB  - The cholinergic pedunculopontine tegmental nucleus, located in the brainstem and
      part of the reticular formation, has been traditionally linked to motor function,
      arousal and sleep. Its anatomical connections, however, raise the possibility
      that the pedunculopontine tegmental nucleus is also involved in other aspects of
      behaviour such as motivation, attention and mnemonic processes. This is of
      obvious importance, since the pedunculopontine tegmental nucleus undergoes
      degeneration in human neurodegenerative disorders also characterized by
      attentional and/or mnemonic deficits. Moreover, recent behavioural animal work
      suggests that cognitive processes may be represented in the pedunculopontine
      tegmental nucleus. The difficulty that faces research in this area, however is
      the possible influence of cognition by other processes, such as arousal state,
      motivation and motor function. Nevertheless, by reviewing the literature, the
      pedunculopontine tegmental nucleus seems to be involved in attentional and
      possibly also in learning processes. These processes could be mediated by
      influencing cortical function via the thalamus, basal forebrain and basal
      ganglia. The involvement of the pedunculopontine tegmental nucleus in mechanisms
      of memory, however, seems to be rather unlikely.

PMID- 7820135
TI  - Calcium-activated non-selective channels in the nervous system.
AB  - In the decade, since the first description of calcium-activated non-selective
      (CAN) channels in cardiac myocytes, pancreatic acini and neuroblastoma, this type
      of channel has been shown to have a ubiquitous distribution across a variety of
      tissues. Recently, their role in the function of cells of the nervous system has
      become better delineated. Because CAN channels pass depolarizing current, respond
      to cytoplasmic Ca2+ activity and do not inactivate, they are capable of producing
      maintained depolarization of neurons. This property endows upon CAN channels an
      important role in both physiological functions and pathological processes of the
      nervous system.

PMID- 7820136
TI  - Stage I nonseminomatous germ-cell testicular cancer--management options and risk
      benefit considerations.
AB  - The results obtained with primary retroperitoneal lymph-node dissection (RPLND)
      in 464 patients with clinical stage A nonseminomatous germ-cell (NSGC) testicular
      cancer over a period of 25 years (1965-1989) were reviewed. Results were analyzed
      in clinical terms and subdivided into early (1965-1978) and contemporary (1979
      1989) findings so as to be comparable with series using radiotherapy or
      surveillance. Between 1965 and 1978 (86 clinical stage A patients), the overall
      relapse rate of 15% (n = 13) was similar to that obtained in radiotherapy series
      but the survival (98.8% after RPLND) was superior to that achieved with
      irradiation (87%). From 1979 to 1989, 378 clinical stage A cases had primary
      RPLND, of whom 29% (n = 111) had cancerous nodes. The relapse rate for
      pathological stage A patients (n = 267) was 11% and two patients died. The rate
      of relapse for pathological stage B patients who did not receive adjuvant
      chemotherapy was 32%. No relapse was seen among 46 pathological stage B patients
      given postoperative adjuvant chemotherapy. The mortality of 0.7% observed among
      378 clinical stage A RPLND cases was lower than the 2% value reported in
      surveillance series. Although not statistically significant, these consistent
      results reported for two eras (pre- and postplatinum) spanning a period of 25
      years suggest a sound basis for the surgical approach. The anatomic and medical
      principles in oncology, which have supported this approach, remain cogent today.
      They are discussed herein. Now that nerve-sparing techniques have been developed,
      the one long-term morbidity of RPLND (i.e., anejaculation) can be
      avoided.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7820137
TI  - Genetic factors in malignant germ-cell tumors.
AB  - The etiology of germ-cell tumors is largely unknown. A history of undescended
      testis is the major known risk factor. Epidemiology studies have established the
      importance of (unknown) environmental factors probably operating very early in
      life. However, there are large differences in incidence in different populations
      and races. Familial cases and patients with bilateral cancer have been described,
      and the incidence is greatly increased in individuals with certain malformations
      of the urogenital system. The latter observations point to a genetic component in
      the disease's etiology. In most germ-cell tumors an isochromosome of the short
      arm of chromosome 12, i(12p), can be demonstrated. This highly characteristic
      cytogenetic aberration can be diagnostic of germ-cell tumors and may have
      prognostic importance. This article summarizes the current knowledge about and
      ongoing research on genes involved in the development of germ-cell tumors.

PMID- 7820138
TI  - Vascular considerations in postchemotherapy. Retroperitoneal lymph-node
      dissection: Part I--Vena cava.
AB  - A total of 42 patients underwent inferior vena cava resection (n = 40) or
      intraluminal tumor thrombectomy (n = 2) during retroperitoneal lymph-node
      dissection (RPLND) for bulky abdominal metastatic nonseminomatous germ-cell
      cancer (7% of all postchemotherapy RPLND cases). The three indications for caval
      resection included tumor clearance (38%), caval scar occlusion (14%), and caval
      tumor thrombus (48%). En bloc caval resection to achieve tumor clearance was
      justified by subsequent nodal pathology (cancer in 63% of specimens, teratoma in
      31% specimens). Caval resection in the presence of scar occlusion was required de
      facto by virtue of its incorporation in the specimen. Caval resection or
      thrombectomy is indicated for intraluminal tumor thrombus because thrombus
      pathology (cancer, 35%; teratoma, 45%; fibrosis, 20%) reflected nodal pathology
      in 71% of cancer cases, 78% of teratoma cases, and 100% of fibrosis cases. The
      complications of caval resection were generally transitory. The 71% survival rate
      justifies this intensive surgical approach because these patients had exhausted
      all chemotherapeutic options.

PMID- 7820139
TI  - Vascular considerations in postchemotherapy. Retroperitoneal lymph-node
      dissection: Part II.
AB  - A total of 710 patients underwent postchemotherapy retroperitoneal lymph-node
      dissection (RPLND) from 1965 to 1992. Ten patients, all with bulky disease,
      required aortic replacement either postoperatively (n = 3) or during RPLND (n =
      7). The principal risk factor for aortic rupture after RPLND was an extended
      subadventitial aortic dissection made necessary by tumor fixation. Also, duodenal
      enterotomy or extensive violation of the bowel serosa was a further risk for
      aortoenteric fistula. Prospective aortic grafting may be indicated in the
      presence of these risk factors. In our four elective cases, there was no further
      vascular or bowel complication. Omental interposition further protects against
      fistula formation. Although rarely indicated except under the most extenuating
      circumstances, the exposure requirements of RPLND permit aortic grafting as a
      relatively straightforward procedure that is feasible and well tolerated in this
      small subset of patients.

PMID- 7820140
TI  - Persistent cancer in postchemotherapy retroperitoneal lymph-node dissection:
      outcome analysis.
AB  - Surgery following chemotherapy for treatment of metastatic testis cancer is
      reserved for partial remissions with localized tumors considered resectable.
      After primary chemotherapy, about 90% will have teratoma or necrosis and only 10%
      will have cancer. The concept of two cycles of post operative chemotherapy in
      this small group with cancer is supported by a 70% long term cure rate. A more
      difficult group of patients are those who have had not only primary but also
      salvage chemotherapy for refractory tumor. About 55% of these patients undergoing
      post (salvage) chemotherapy RPLND surgery have persistent cancer in the resected
      specimen. There is no data to support the routine use of repeat salvage
      chemotherapy post operatively. Of 91 patients presenting for surgery post salvage
      chemotherapy, 53 were considered completely resected and 36 incompletely
      resected. Of the 53 realistic candidates for cure with complete resections, 25
      were given post operative repeat salvage chemotherapy and 28 received none. 9
      (36%) receiving more chemotherapy remained NED and 12 (43%) receiving none
      remained NED. 12 in each group died of disease. Therefore, there is no data to
      support routine repeat salvage chemotherapy in patients considered completely
      resected who had already received salvage chemotherapy pre-operatively. Rather
      the outcome in this cohort depends more on the completeness of its resectability.

PMID- 7820141
TI  - Size and status of metastases after inductive chemotherapy of germ-cell tumors.
      Indication for salvage operation.
AB  - Secondary resection of metastases remaining after inductive chemotherapy of
      advanced germ-cell tumors has thus far been obligatory. The absence of malignant
      components in one-third of all residual tumors and the high risk of the operation
      have led several authors to reconsider the criteria for this approach. In a
      retrospective study of 153 cases (127 evaluable) we investigated the histology of
      the primary tumor and the size of the residual tumor with regard to residual
      histology and outcome. Patients were divided into the following three groups
      according to the histology of the primary tumor: group I, pure seminoma (16
      patients); group II, nonseminoma without teratoma (32 patients); and group III,
      nonseminoma with teratoma (79 patients). Among the 16 purely seminomatous tumors,
      the residual masses ranged from 2 to 12 cm; 12 consisted of necrotic tissue only,
      3 contained malignant germ-cell elements, and 1 contained adult teratoma. The
      residuals of primarily teratoma-free nonseminomas measured 2-16 cm; the smallest
      residual tumor containing active malignant elements measured 4 cm, and the
      diameter of the largest necrotic residue was 6 cm. Four residuals contained
      mature teratoma. The size of residuals from teratomatous primary tumors was 3-24
      cm; the smallest malignant tumor measured 5 cm, and the diameter of the largest
      purely necrotic mass was 8 cm. According to our results, a secondary operation
      may be omitted if the residual mass of a primary seminoma is smaller than 5 cm or
      if that of a primary nonseminoma without teratoma is less than 3 cm in
      diameter.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7820142
TI  - Unusual neoplasms detected in testicular cancer patients undergoing
      postchemotherapy retroperitoneal lymphadenectomy.
AB  - Approximately 30% of patients with disseminated testicular cancer who receive
      platinum-based chemotherapy will experience normalization of tumor markers but
      have persistent, radiographically evident disease in the retroperitoneum. These
      patients are usually subjected to retroperitoneal lymph-node dissection (RPLND).
      In all, 45 of 557 patients (8.1%) undergoing postchemotherapy RPLND at Indiana
      University Medical Center (IUMC) were found to have neoplastic elements distinct
      from the classic germ-cell tumor types within their resected specimens. Examples
      included various sarcomas in 14 patients (3.7%), other nonsarcomatous non-germ
      cell cancers in 18 patients (3.2%), and cystic atypical choriocarcinoma in 8
      patients (1.4%). No distinct patient characteristic or histologic pattern in the
      primary tumor was predictive of these unusual findings in the RPLND specimen,
      although sampling error in the orchiectomy specimen could be the reason for this
      lack of correlation. Surgical resection of these chemoresistant tumors is
      potentially curative, with disease-free survival being obtained in 13 of 19
      patients (68.4%) with sarcoma, 10 of 18 patients (55.6%) with nonsarcomatous
      cancers, and 7 of 8 patients (87.5%) with cystic atypical choriocarcinoma at mean
      follow-up intervals of 30.6, 42.5, and 24.7 months, respectively.

PMID- 7820143
TI  - Treatment intensification in disseminated germ-cell tumors.
AB  - Despite major improvements in the treatment of germ cell tumors the results
      remain unsatisfactory in patients with "poor risk" initial presentation, with
      inadequately responding or relapsed disease. The alternating use of
      noncrossresistant drugs or dose-intensified treatment regimens have not proved to
      be superior to conventional regimens, although the role of early treatment
      intensification with the use of hematopoetic growth factors or hematopoetic stem
      cell reinfusion warrants further investigation. In phase I/II trials patients
      considered incurable with conventional treatment regimens have been successfully
      salvaged by high-dose chemotherapy and autologous stem cell reinfusion. Several
      phase III trials to define the role of this novel approach are planned or ongoing
      in the USA and Europe.

PMID- 7820144
TI  - Chemoresistance of renal cell carcinoma: 1986-1994.
AB  - Multidrug resistance (MDR) in a variety of human tumors such as renal cell
      carcinoma (RCC) is thought to be caused by expression of the mdr1 gene and may be
      reversed by applying chemosensitizers such as Dexverapamil that inhibit the mdr1
      gene product P-glycoprotein. On the basis of our preclinical analysis, we
      initiated a clinical (GCP) study with vinblastine (VBL), the most effective--if
      at all--chemotherapeutic agent; dexverapamil; and dexamethasone in patients with
      RCC. All patients had histologically proven RCC that was metastatic and
      progressive at study entry. The statistical design featured a preliminary study
      of two cycles of VBL alone followed by tumor evaluation. If no response was
      documented, with all patients thus serving as their own control, dexverapamil and
      dexamethasone were added for a minimum of three cycles of combination therapy.
      Having obtained institutional permission by the ethical review committee (MEC
      124, 106-1993/12), we enrolled 24 patients on this protocol starting on May 3,
      1993. In the preliminary study, 1 complete response (CR) was achieved with VBL
      alone, and myelotoxicity led to an adequate dose reduction from 2 mg/m2 VBL per
      day given as a 5-day continuous infusion (days 1-5) in 6/10 yet evaluable
      patients to 1.4 mg/m2 per day. In 8/11 yet evaluable patients, dexverapamil doses
      reached > or = 3000 mg/day by 7-day oral uptake (days 0-6, supported by 20 mg
      dexamethasone given twice daily), which is significantly higher than those
      previously reported. The combination of VBL given at 1.4 mg/m2 per day plus,
      dexverapamil given at 3000 mg per day was felt to be safe and well tolerated.
      Nine patients were yet evaluable for response. One partial response and three
      minor responses were noted in this heavily pretreated study population. It
      appears that this innovative approach may have some activity in RCC and may
      eventually lead to a rational treatment modality. Careful evaluation in ongoing
      studies is warranted.

PMID- 7820145
TI  - [Correction of anemia in chronic kidney failure with lyophilized recombinant
      human erythropoietin using a subcutaneous approach].
AB  - The recombinant human erythropoietin (rHuEPO) by subcutaneous route has been
      considered the drug of choice for the correction of the anemia of chronic renal
      patients. PURPOSE--To evaluate the efficacy of a new preparation of rHuEPO in the
      correction of the anemia of chronic renal patients maintained by haemodialysis,
      exclusively administered by subcutaneous route, studying the adverse effects and
      searching for predictive factors for the response to this medication. METHODS-
      Twelve patients in regular haemodialysis were treated with freeze-dried rHuEPO by
      subcutaneous route during 18 months with initial doses of 20U/kg/dialysis. They
      were submitted to a careful clinical and laboratory monitoring for all this
      study. RESULTS--Eleven patients ended the study reaching the target hematocrit
      (Htc) of 30% and keeping it during the whole period of the study. The mean
      correction and maintenance doses of rHuEPO were 65U/kg/dialysis and
      51U/kg/dialysis respectively. At the 12th week of the study a significative
      increase of Htc (18.4 +/- 3.5% vs. 25.4% +/- 3.8%, p < 0.05) was demonstrated. An
      increase of the erythrocytes and hemoglobin was concomitantly observed.
      Leucocytes and platelets increased significantly from the 24th week and kept
      steadily until the end of study. Just potassium increased in the biochemistry
      analysis of the patients at the 4th and the 12th week of the study returning to
      the basal values at the 24th week. The evolution of the iron metabolism
      parameters demonstrated an intermitent and statistically significant decrease of
      transferrin saturation at the 1st, 12th and 24th week, returning to the basal
      levels at the end of study. The serum ferritin did not change (582.7 +/- 700,
      9ng/mL vs. 700.0 +/- 651, 6ng/nL). The weight and the blood pressure did not
      change either, although 2 normotensive patients became hypertensive and 2 others
      with controlled hypertension needed drug rearrange for blood pressure control
      (36%). A patient had a seizure episode with a full recovery. CONCLUSION--The
      rHuEPO has proved to be a safe and an efficient drug with easily controlled
      adverse effect.

PMID- 7820146
TI  - [The role of percutaneous renal biopsy in kidney transplant].
AB  - Percutaneous renal biopsy (PRB) is an useful tool for diagnostic and therapeutic
      orientation in renal transplantation. PURPOSE--To evaluate the current role of
      PRB in post-transplant acute renal dysfunction (ARD) of renal allografts. METHODS
      -Sixty-five renal transplant patients were submitted to 95 valid renal biopsies
      with no major complications. RESULTS--There was disagreement between the clinical
      and the pathological diagnosis in 28 occasions (29.5%). In 36 cases (37.9%) the
      results of the pathological examination led to a modification in patient's
      management. These modifications were most commonly the avoidance or witholding of
      a steroid pulse (8 cases); nephrectomy of the renal allograft (8 cases);
      witholding or decrease of cyclosporine dosage (6 cases); giving a steroid pulse
      (5 cases) and giving antibiotics to treat acute pyelonephritis in 4 cases. The
      use of kidneys from cadaveric donors was significantly associated with an
      increased number of biopsies (p < 0.05). CONCLUSION--These results demonstrate
      that even though several less invasive procedures are currently employed, renal
      biopsy is still an indispensable method to the management of ARD in renal
      transplant patients.

PMID- 7820147
TI  - [Conservative surgery of splenic trauma in children].
AB  - The spleen is an important component of the immunologic system, especially in
      children. Splenectomy may result in immunologic deficiency, and splenic salvage
      is recommended as management in splenic surgery. PURPOSE--Splenic injury
      management, considering splenic salvage as a safe therapeutic option in these
      children. METHODS--One hundred and thirty nine (139) children, aged 5 months to
      12 years were at Joao XXIII Hospital, Belo Horizonte, Brazil, for the period of
      1981 to 1990. The causes of the trauma, the extent and the management of splenic
      injuries were evaluated. Hemodynamic instability with shock occurred in 30% of
      the children. The contusions were responsible for injury in 135 patients (97.2%)
      with 58.7% caused by pedestrian/motor vehicle accidents 41.6% of splenic injury
      were grade I and II, 30.6% were grade III, and 26.5 grade IV e V (Injury Scalling
      Committee). RESULTS--Non operative management was done in 2 patients and 137 were
      operated on. Conservative surgery was performed in 98 patients (71.5%), which
      included: splenorraphy in 81 (82.6); partial splenectomy in 10 (10.2%), and
      laparotomy followed by observation in 7 (7.1%). Post-surgical hemorrhage occurred
      in one case after conservative surgery. Splenectomy was performed in 39 (28.5%)
      of the patients with 75-100% of the splenic injury classified in grades IV and V.
      Multiple associated lesions occurred in 87 children (62.5%). The mortality rate
      was 10.5%. Cranioencephalic trauma was the cause of death in 13 children.
      CONCLUSION--The splenic salvage is a possible option in the management of splenic
      injury in 70% of the cases. Nonoperative treatment of splenic injury depends on
      the physiologic status of the patient, CT scan demonstration of splenic injury
      and intensive care management. If there was an associated abdominal injury, there
      would be an indication for surgery.

PMID- 7820148
TI  - [Intrahepatic cholestasis with situs inversus of the liver].
AB  - Intrahepatic cholestasis with situs inversus of the liver has not been reported
      in the literature. PURPOSE--A follow-up case for approximately 14 years (by one
      of the authors, MM). METHODS--Clinical aspects were studied and several
      laboratory exams as well as three ultrasonography and one computerized tomography
      exams were performed. Percutaneous and endoscopic cholangiographies were
      attempted. RESULTS--Four days after the patient was submitted to a surgical
      replacement of the aortic valve (with extracorporeal circulation), she developed
      jaundice, severe pruritus, dark urine, and pale stools. Serum levels of
      bilirubin, alkaline phosphatase, gama-glutamil transferase, and cholesterol were
      very high. Ultrasonography and computerized tomography exams did not reveal any
      evidence of extrahepatic obstruction. The tomography exam confirmed the existence
      of situs inversus in the stomach and liver. We were not successful in performing
      the cholangiography exams. Clinical and laboratory data as to cholestasis
      returned to normal after 4 months with no recurrence or complication during the
      follow-up period (14 years). CONCLUSION--The differential diagnosis between intra
      and extra-hepatic cholestasis in patients with situs inversus of the liver may be
      difficult. Therefore it will be necessary to collect clinical data and various
      complementary exams such as endoscopic retrograde cholangiopancreatography which
      is very difficult to perform in these patients.

PMID- 7820149
TI  - [Menopause and risk factors for coronary disease].

PMID- 7820150
TI  - [Mechanisms of tumoral resistance to antineoplastic agents].

PMID- 7820151
TI  - [Heart rate variability: significance and clinic application].

PMID- 7820152
TI  - Malignant tumors among Gaviao Indians. Proximity of electromagnetic fields.

PMID- 7820153
TI  - [Clinical and epidemiological aspects of AIDS in the Hospital of the Federal
      University of Mato Grosso].

PMID- 7820154
TI  - [Teicoplanin and vancomycin susceptibility in Staphylococcus aureus and coagulase
      negative staphylococci].
AB  - Members of the genera Staphylococcus are the most common pathogens found in the
      hospital environment and they are acquiring resistance to multiple drugs. PURPOSE
      -To evaluate the in vitro activity of teicoplanin and vancomycin against 195
      strains of staphylococci isolated from in-patients. METHODS--One hundred strains
      of Staphylococcus aureus (50% methicillin-resistant) and 95 strains of coagulase
      negative staphylococci (46.3% strains methicillin-resistant) were tested by the
      agar dilution and the disk diffusion techniques. RESULTS--All strains (100%) were
      susceptible to vancomycin, S. aureus strains presented MIC90 of 0.5 microgram/mL
      whereas strains of coagulase-negative staphylococci showed MIC90 of 1.0
      microgram/mL. For teicoplanin, 98.5% of the strains were susceptible. MIC90
      values were 0.5 microgram/mL for S. aureus strains, 2.0 micrograms/mL for
      coagulase-negative methicillin-susceptible staphylococci strains and 8.0
      micrograms/mL for coagulase-negative methicillin-resistant staphylococci strains.
      CONCLUSION--From the microbiological point of view, the results showed a high
      potential for both drugs as therapeutic agents in staphylococcal infections due
      to multiresistant strains of hospital origin.

PMID- 7820155
TI  - [Hospital organizational structure].
AB  - The basic point for an Institution to work is the existence of a definite
      organizational structure that puts together similar areas allowing decisions and
      the operationalization of different tasks. Knowledge and analysis of structures
      of private and public hospitals and a bibliography review about the issue is the
      purpose of this paper. Suggestions are given about the elaboration of small
      structures and the utilization of matrix management in order to accomplish the
      hospitals objectives.

PMID- 7820156
TI  - [Human infection by Hantavirus in southern and southeastern Brazil].
AB  - The results of serological investigation on Hantavirus antibodies carried out
      between February 1986 and August 1990 in human populations of the States of Sao
      Paulo and Parana, Brazil, which had close contact with urban rats or wild rodents
      and others small mammals are described. OBJECTIVE--To identify the human
      infection caused by Hantaviruses, which are the etiological agents of Hemorrhagic
      fever with renal syndrome. METHODS--Sera from 1063 persons were tested by enzyme
      immunoassay (ELISA) to Hantaan, Seoul and Puumala antigens. Plaque reduction
      neutralization test to the same antigens and indirect immunofluorescent test to
      Hantaan antigen were performed in the positive sera. RESULTS--Antibodies to
      Hantaan, Seoul or Puumala viruses were detected in 32 persons by enzyme
      immunoassay (ELISA) and immunofluorescent test. Plaque reduction neutralization
      test performed in these 32 sera were positive in 5 (3 for Puumala and 2 for Seoul
      viruses). One serum reacted with high titer to Seoul virus in all tests. It was
      from a male resident in the rural area of Ribeira Valley, State of Sao Paulo,
      where he was born and has always lived. He had only travelled inside the State of
      Sao Paulo. CONCLUSION--There are serological evidences of Hantavirus infections
      in residents of the rural areas of the Amparo Island, Paranagua Bay, State of
      Parana and the Ribeira Valley, State of Sao Paulo; in employees of the port of
      Paranagua, State of Parana and in patients of the Emilio Ribas Hospital, Sao
      Paulo, State of Sao Paulo, who had a presumptive diagnosis of leptospirosis.

PMID- 7820157
TI  - [Lymphedemas of the lower limbs: a lymphoscintigraphic study].
AB  - Patients with lymphoedema of the lower limbs (LLL) are usually affected by
      recurrent erysipelas. This bacterial infection is usually admitted as an
      aetiological factor, but it can be a consequence of some previous lymphatic
      abnormality. Classically, the commonest causative factors of LLL are bacterial
      infection, venous ulcers, trauma (leading to secondary lymphoedema) and
      congenital disorders of the lymphatic system (primary lymphoedema--praecox or
      tarda). PURPOSE: To identify previous lymphatics abnormalities in patients with
      LLL, admitted as having secondary lymphatic lymphoedema--as consequences of
      infection, trauma or other factors--, by using lymphoscintigraphic method. To
      observe advantages of this approach in practical assistance and evaluation of LLL
      cases. METHODS: Twelve patients with LLL, supposed to have primary (congenital)
      or secondary disorder affecting one or both lower extremities were submitted to
      lymphoscintigraphy at the Escola Paulista de Medicina of Sao Paulo, Brazil. Each
      patient received an intradermal injection of labelled Dextran (Dx-99mTc) at the
      first interdigital space of each foot and, after one to three hours, images of
      lower extremities, pelvic and abdominal areas were obtained with Gammatome CGR.
      RESULTS: Examination of all 24 lower extremities disclosed clinical diagnosis of
      lymphoedema in 17 (70.8%), being five (41.6%) with clinical signs of lymphoedema
      of both lower limbs and seven (58.3%) of a single one. The lymphoscintigraphic
      images revealed lymphatic disorders in 22 of the 24 extremities (91.7%).
      Lymphoscintigraphic abnormalities in clinically normal lower extremities were
      observed in five cases (41.3%). CONCLUSION: Lymphoscintigraphy is a non-invasive
      useful method to study LLL, with involvement of one or both limbs. It does not
      differentiate between primary and secondary lymphoedema, but makes possible to
      detect cases of normal appearance of the limbs with previous lymphatic defect(s),
      changing aetiological diagnosis. Some cases that appear to be secondary
      lymphoedema could be, in fact, associated with congenital abnormality(ies) of
      lymphatics, triggered by factors like trauma or venous ulcers.

PMID- 7820158
TI  - Transvaginal color Doppler ultrasonography in reproductive gynecology.
AB  - Transvaginal color Doppler sonography (TVSCD) is one of the most important recent
      developments in gynecology. TVSCD provides relevant information on uterine and
      ovarian blood flow and aids in the identification of pregnancy viability as well
      as the early diagnosis of ectopic pregnancy. TVSCD also facilitates differential
      diagnosis of benign and malignant pelvic pathology.

PMID- 7820159
TI  - Osteoporosis prevention with sex hormone replacement therapy.
AB  - It was suggested as long ago as 1941 that there might be a connection between the
      menopause and osteoporosis. Since then, abundant data have confirmed that
      hypothesis as well as showing that such osteoporosis may be prevented by estrogen
      supplementation (ERT--estrogen replacement therapy). In estrogen deficiency,
      increased bone resorption takes place in the process of bone remodeling, leading
      to bone loss. The bone loss occurs universally but to the greatest extent at
      sites rich in trabecular bone. There are uncertainties concerning extent of bone
      loss at various sites at different ages, effect of ERT at varying sites and
      different ages, degree of fracture prevention, and relationship between duration
      of therapy and fracture risk. That optimal fracture risk is not being attained
      now on a population basis is due to apparently low acceptance of ERT by patients
      and lack of strenuous effort in that direction by physicians.

PMID- 7820160
TI  - Luteal phase hyperprolactinemia.
AB  - OBJECTIVE: To determine the incidence of both isolated and repetitive prolactin
      elevations in the luteal phase of otherwise normoprolactinemic women. To see if
      sporadic luteal-phase hyperprolactinemia is associated with progesterone
      deficiency, and to explore a possible physiological basis for sporadic
      hyperprolactinemia by TRH challenge. SETTING: Hospital-based reproductive
      endocrinology/infertility service. DESIGN: Prospective measurement of luteal
      phase serum progesterone and prolactin in normoprolactinemic ovulatory women. TRH
      stimulation testing in volunteers with repetitive luteal phase hyperprolactinemia
      and normoprolactinemic controls. PATIENTS: 133 sequentially selected infertile,
      ovulatory women with normal prolactin levels in the proliferative phase of the
      cycle. INTERVENTIONS: Measurement of serum progesterone and prolactin during the
      luteal phase, based on the day of the LH surge. TRH testing in the midluteal
      phase of the cycle in patients with two or more luteal phase prolactin
      elevations, and in five normoprolactinemic volunteers in both the preovulatory
      and midluteal phase. RESULTS: Of 133 subjects, 85 (64%) had no prolactin level
      exceeding 20 ng/mL in the luteal phase. Thirty-three (25%) had two or more
      elevated levels, and were considered to have repetitive luteal phase
      hyperprolactinemia (LPH). TRH testing in control subjects resulted in a greater
      prolactin response in the preovulatory phase. The group with LPH demonstrated an
      initial elevation of prolactin greater than that of the normoprolactinemic
      controls, but a subsequent drop to levels lower than both preovulatory and
      midluteal normoprolactinemic controls by 45 minutes. CONCLUSIONS: Sporadic luteal
      phase hyperprolactinemia is a relatively common event (36% of 133 subjects in the
      present series). Of these 48 women, 33 (69%) had repetitive elevations,
      suggesting the elevation in these subjects to be more than a random event. The
      physiological validity of this observation is further demonstrated by an abnormal
      response to TRH stimulation, but the normal levels of luteal phase progesterone
      leave questions as to its pathological importance.

PMID- 7820161
TI  - Effect of long abstinence periods on human sperm quality.
AB  - OBJECTIVE: To evaluate the effects of long abstinence periods on semen
      characteristics. DESIGN: Semen analysis was performed on six men after various
      sexual abstinence periods (from 2 to 18 days). The variations in semen parameters
      were analyzed statistically as a function of the duration of abstinence. SETTING:
      The Reproductive Biology Laboratory at the University of Montpellier Medical
      School. RESULTS: Lengthy sexual abstinence was found to affect all semen
      characteristics. Semen volume and concentration and total sperm count showed
      significant increases, whereas motility and normal morphology decreased
      significantly with duration of abstinence. Significant changes in the percentage
      of normal sperm forms were observed after more than seven days' abstinence.
      CONCLUSION: The study indicates that the influence of long sexual abstinence on
      semen quality varies with the variable considered. With regard to fertility, a
      long abstinence period might induce senescence of spermatozoa.

PMID- 7820163
TI  - Effect of cadmium and cigarette smoking on human semen quality.
AB  - OBJECTIVE: In recent years, there have been many nonconclusive studies on
      cigarette smoking and sperm quality. Few studies, if any, have attempted to
      implicate any decrease of sperm quality. The aim of this study was to examine the
      relationship between cigarette smoking, blood and seminal plasma concentrations
      of cadmium and lead, and sperm quality. METHODS: A total of 184 males who were
      undergoing initial screening for infertility were included in the study. Tests
      conducted included semen characteristics (volume, total sperm count, sperm
      viability, motility and morphology of spermatozoa), and blood and seminal plasma
      concentrations of lead and cadmium. RESULTS: More than 50% and 70% of the
      subjects had normal sperm density and motility, respectively. The mean
      concentrations of lead in blood (PbB) and seminal plasma (PbS) were 7.09
      micrograms/dL and 12.98 micrograms/L, respectively, while the mean concentrations
      of cadmium in blood (CdB) and seminal plasma (CdS) were 0.95 micrograms/L, and
      0.58 micrograms/L, respectively. Significant correlations were observed between
      CdB and cigarette-years and sperm density (negative). CdS was significantly
      correlated with cigarette-years and sperm volume (negative). Significant trends
      were observed for different categories of cigarette-years with CdB, CdS and sperm
      density. CONCLUSION: Cigarette smoking appears to affect sperm density,
      especially in heavy smokers. Cadmium (present) in cigarettes could be a possible
      causative agent for the low sperm density among smokers.

PMID- 7820162
TI  - A two-year clinical study of the effects of two triphasic oral contraceptives on
      plasma lipids.
AB  - OBJECTIVE: Oral contraceptive formulations can alter plasma lipid and lipoprotein
      levels; however, lower-dose triphasic tablets show only minimal metabolic effects
      during 6 or 12 cycles of use. Involvement of lipids in chronic cardiovascular
      conditions, plus long-term use of oral contraceptive tablets, prompted this first
      24-cycle study of the effect of triphasic formulations on young women. METHODS:
      69 women assigned randomly to an ethinyl estradiol/levonorgestrel formulation
      (Triphasil) or an ethinyl estradiol/norethindrone formulation (Ortho 7/7/7) and
      25 control women (no hormonal contraception) had blood sampled for lipids and
      lipoproteins pre-trial, and at 3- or 6-cycle intervals for 24 cycles. RESULTS: At
      cycle 24, control women experienced no significant change from baseline in any
      variable except apolipoprotein B (apo B). Plasma apo B increased 42% (P < .01),
      reflecting the LDL apo B increase (42%, P < .01). Both combination formulations
      significantly increased apo B (plasma, VLDL, IDL and LDL); the increases ranged
      between 47% and 84%. Plasma apo A1 rose (15%, P < .001) in the Ortho 7/7/7 group
      only. Plasma and LDL triglycerides were increased significantly (P < .001) by the
      norethindrone product, 43% and 81%, respectively, and plasma and LDL cholesterol,
      14% and 28%, respectively. Cholesterol decreased in all other subfractions,
      including HDL (11%, P < .01). HDL cholesterol decreased significantly in the
      Triphasil group (8%, P < .05); no other cholesterol subfractions changed
      significantly. All cycle-24 lipid and lipoprotein values remained well within
      respective normal ranges. CONCLUSION: Although 2-year exposure to the triphasic
      oral contraceptive formulations changed the lipid risk factors for cardiovascular
      disease only within normal ranges, there remains potential for long-term health
      effects when compounded with other risk factors.

PMID- 7820165
TI  - Hospital pushes envelope on federal antitrust laws.

PMID- 7820164
TI  - Nuclear presence of two lysosomal enzymes in rat implantation sites.
AB  - OBJECTIVE: To test the Szego hypothesis of increased beta-glucuronidase and acid
      phosphatase activities in hormone target tissues. METHODS: The presence of beta
      glucuronidase and acid phosphatase activities in nuclear subcellular fractions
      obtained from decidual (implantation site) and stromal (nonimplantation zone)
      tissues was demonstrated by both biochemical measurements and ultramicrographic
      analysis utilizing a histochemical reaction. RESULTS: Acid phosphatase was almost
      twice as abundant in nuclei and lysosomes of epithelial cells (implantation
      sites), and beta-glucuronidase also was significantly more active in nuclei from
      epithelial and decidual tissues than in nonimplantation tissue. CONCLUSION: Our
      results, utilizing the implantation process as experimental model, support the
      Szego hypothesis of the lysosomal role in hormonal mechanisms of action.

PMID- 7820166
TI  - Can we make a new deal? Entitlement reform sounds alluring, but the reality is
      stark.
AB  - After simmering for more than a decade, the Great Entitlement Debate promises to
      dominate the 1995 congressional agenda. But lost amid a tangle of conflicting
      parochial interests, voter confusion and searing partisan rhetoric are some harsh
      truths about our options.

PMID- 7820167
TI  - Building healthier communities. Neighbor to neighbor, brick by brick.
AB  - From rural Bladen County, NC, to central Harlem in New York to Toms River, NJ,
      hospitals are shredding red tape and blasting organizational boundaries to serve
      the broadest needs of their communities. For their collaborative work, Hospitals
      & Health Networks and the American Hospital Association salute this year's NOVA
      Award winners.

PMID- 7820168
TI  - The paradox of change.
AB  - Is health care totally unique? Or are we facing challenges akin to those in the
      larger world? An analysis drawing on the leading edge in management thought
      examines the change dynamic washing over the business world--and uncovers some
      startling lessons for health care.

PMID- 7820169
TI  - Mr. Smith goes to Washington?. Interview by Renee Blankenau.
AB  - The five freshman congressmen we're profiling in this issue have a lot more going
      for them than Mr. Smith did; most importantly, all bring strong community health
      and welfare concerns to Capitol Hill. A look at representatives of a sometimes
      surprising new crop of citizen-lawmakers.

PMID- 7820170
TI  - Sexually harassed.
AB  - When neurosurgeon Frances Conley resigned her Stanford University Medical School
      professorship over sexual harassment, her case received widespread notoriety. But
      Conley is far from alone in health care.

PMID- 7820171
TI  - San Diego. As a market matures, networks feel growing pains.

PMID- 7820172
TI  - Fighting the 'vampire effect.' Is health care heading for a corporate takeover?

PMID- 7820173
TI  - Profile. Linda Bremner--founder, Love Letters Inc.

PMID- 7820174
TI  - Modeming home. Kaiser's home health staff gives telecommuting a spin.

PMID- 7820175
TI  - Reengineering the old-fashioned way.

PMID- 7820176
TI  - Sim-surgery. Radiologists remove 'virtual' from virtual reality.

PMID- 7820177
TI  - A dog day rebound.

PMID- 7820178
TI  - A kinder, gentler biopsy?

PMID- 7820179
TI  - Robodoc booster.

PMID- 7820180
TI  - Revisiting our ideas about health.

PMID- 7820181
TI  - Cancer biotherapy: the first year.

PMID- 7820182
TI  - The clinical experience with interleukin-2 in cancer therapy.
AB  - In May 1992, interleukin-2 (IL-2) was formally approved by the U.S. Food and Drug
      Administration for use in cancer treatment based on its activity in metastatic
      renal cell carcinoma. IL-2 alone or in combination with activated lymphocytes or
      other cytokines has significant anti-tumor activity against renal cell carcinoma
      and melanoma with response rates of 15-20%, some of which are quite durable.
      Limited anti-tumor effects have been noted in some patients with colorectal
      cancer and lymphoma. Too few patients have been studied to establish the level of
      activity in most other specific tumor types. The mechanism of this anti-tumor
      effect appears to be entirely mediated by the immunostimulatory effects of IL-2.
      Toxicities are dose related, but are substantial and similar regardless of the
      schedule of administration. Randomized trials have failed to establish (1) the
      superiority of high-dose bolus over continuous infusion IL-2, (2) the superiority
      of IL-2 plus interferon over IL-2 alone, or (3) the superiority of IL-2 plus LAK
      cells versus IL-2 alone. Further investigation is needed to determine the optimum
      dose and schedule from the standpoint of cost:benefit and risk:benefit, and to
      determine the role of IL-2 in the therapy of other malignant diseases.

PMID- 7820183
TI  - Growth of tumor derived activated T-cells for the treatment of cancer.
AB  - This report describes the production of Tumor Derived Activated Cell cultures
      (TDAC, also called tumor infiltrating lymphocytes) from patient tumor biopsies
      and our preliminary experience growing these cells to therapeutic levels using
      artificial capillary bioreactor cultures. TDAC were successfully grown in medium
      containing Interleukin 2 from 80% of the 113 tumor biopsies tested. There was no
      significant difference in success (growth to 1 x 10(9) cells) comparing primary
      and metastatic tumors. Many of the tumors were shipped to the laboratory from
      distant sites. Success rate did decrease with the length of time for tumor
      transport. Interleukin 4 was beneficial in the development of 1 of 4 TDAC
      cultures which did not grow with IL-2 only. Seventy-seven bioreactor cultures
      were initiated for 31 patients. On the average, 1.9 x 10(9) TDAC were inoculated
      per bioreactor; 3.3 x 10(10) were harvested in 22 days. Twelve liters of medium
      were required per 1 x 10(10) TDAC produced. TDAC cultures contained T cells with
      variable ratios of CD4 to CD8 cells. Secreted granulocyte monocyte colony
      stimulating factor, interferon gamma and tumor necrosis factor were measured in
      the bioreactor cartridge conditioned medium. Twenty three patients were
      evaluated. Partial responses were observed in 4 patients including a dramatic
      remission of scalp nodules in a patient with renal cancer. Results showed that
      therapeutic amounts of TDAC cells may be produced in a reasonable and cost
      effective manner using artificial capillary bioreactor cultures.

PMID- 7820184
TI  - Induction of cytokines and cytotoxicity against tumor cells by Newcastle disease
      virus.
AB  - The use of NDV as biological adjuvant in vaccines against human cancer is still
      actual in several clinical treatment protocols. In this study, we have
      investigated in vitro-effects of Newcastle disease virus (NDV) strain 73-T on
      isolated mononuclear blood cells and cultured tumor cells. Cellular cytotoxicity
      of PBMC freshly isolated from healthy donors against tumor cells was enhanced
      significantly (p < 0.01) after coincubation of NDV with effector cells. NDV
      failed to enhance cytotoxicity of effector cells when PBMC were stimulated three
      days with 500 IU recombinant interleukin-2 (rIL-2) per ml prior to coincubation
      with the virus. No significant enhancement of cellular lysis was seen when only
      target cells were coincubated with NDV. As shown by depletion of various
      lymphocyte subsets, NK cells were the predominant mediator of lysis. Enhancement
      of cytotoxicity correlated with the induction of interferon-alpha (IFN-alpha) in
      PBMC by NDV. NDV also induced high amounts of tumor necrosis factor-alpha (TNF
      alpha) in PBMC. Induction of interferon-gamma (IFN-gamma) was weak. A direct
      cytopathic effect (CPE) of NDV on different target cells was detected by
      colorimetric measurement of metabolic cell activity. The human tumor cell lines A
      498, A-704, Caki-1, Caki-2, and K-562 and the fibroblast line MRC-5 showed
      progressive cellular destruction 48 h after infection with NDV, whereas PBMC and
      Daudi cells remained unaffected during the observation period. The nontransformed
      monkey kidney cell line CV-1 and the transformed monkey kidney cell line COS-1
      were both lysed by NDV with marginal difference in time course of CPE. Our
      results indicate a reasonable potential of pleiotropic modifications of the
      immune response against tumors by NDV.

PMID- 7820185
TI  - Induction of lymphokine-activated killer (LAK) activity in canine lymphocytes
      with low dose human recombinant interleukin-2 in vitro.
AB  - Interleukin-2 (IL-2) is an immunostimulatory cytokine that induces activation of
      peripheral blood lymphocytes (PBL) which can mediate augmented tumor
      cytotoxicity. Several regimens using IL-2 as treatment for metastatic melanoma
      and renal carcinoma have shown measurable tumor responses in 10-20% of human
      patients. Our overall goals are to determine the efficacy of IL-2 as an adjuvant
      treatment for canine tumors. In order to evaluate the possibility to extend the
      use of IL-2 in vivo in the dog, we examined the ability of a clinically relevant
      (low) dose of human recombinant IL-2 (100 units/ml) to enhance the tumoricidal
      properties of canine PBL in vitro. This was particularly important considering
      the need to establish the effects on canine PBL by IL-2 at a dose that is
      potentially achievable in vivo with acceptable side effects. Our data show, for
      the first time, the ability to separate canine natural killer (NK) cell activity
      from lymphokine-activated killer (LAK) cell activity (induced with a low IL-2
      dose) mediated by canine PBL against two canine cell lines (CTAC and CML-10) used
      as targets in 4 vs. 16 hour killing assays. LAK cells generated by stimulation of
      canine PBL with 100 units/ml of IL-2 for 72 hours, could kill CTAC or CML-10
      targets up to 11 or 18 times more efficiently, respectively, than fresh PBL in a
      4 hour assay. However, the killing of efficiency of the LAK cells was only 2- to
      3-fold greater than that of the fresh PBL in a 16 hour assay. This apparent
      reduction in the killing efficiency of the LAK cells was mostly due to increased
      spontaneous NK activity by the fresh PBL after 16 hours in culture; both the LAK
      cells and the fresh PBL (NK cells) mediated a greater overall cytotoxicity after
      16 hours than they did in the 4 hour assays. These results indicate that a low
      dose of human recombinant IL-2 can augment tumor killing by canine PBL in vitro,
      and suggest that it may be feasible to examine the potential use of IL-2 as an
      immunotherapeutic agent in tumor-bearing dogs.

PMID- 7820186
TI  - Improved delivery through biological membranes. LXI: Design, synthesis, and
      evaluation of a lipolol-based intradermal drug targeting system for 5
      fluorouracil.
AB  - This report describes initial studies with the lipolyl ester of 1
      carboxypropylcarbamoyl-FU (LE-CPCFU) which was designed to enhance the dermal
      delivery of the antitumor agent 5-fluorouracil (FU). The design of LE-CPCFU was
      based upon our previous observation that sulfur-based chemical drug targeting
      systems were localized within the skin and improved the delivery of the parent
      drug to the dermal tissue (Chikhale et al., 1993; Bodor et al., 1982; Bodor and
      Sloan, 1982). In the in vitro test system that used freshly-excised guinea-pig
      skin, LE-CPCFU was found to enhance FU delivery to the skin 2- to 5-fold compared
      to underivatized FU. Neither LE-CPCFU nor its acid metabolite 1
      carboxypropylcarbamoyl-FU (CPCFU) could be detected in the skin or receiver
      during the diffusion experiments even though LE-CPCFU and CPCFU were found to be
      reasonably stable in aqueous pH 7.4 buffer and during the analytical procedure.
      FU which was released from LE-CPCFU in the skin subsequently diffused into the
      receiver. Thus, LE-CPCFU was observed to improve FU delivery to the skin during
      the initial time period of the study (0-4 hr). This study indicates that LE-CPCFU
      in the guinea-pig skin was hydrolyzed to form FU in the skin serving as an
      intradermal drug delivery system for the antitumor agent. Thus, LE-CPCFU could
      prove to reduce the systemic toxicity of FU by enhancing the local skin
      concentration and minimizing the systemic concentration of the antitumor agent as
      compared to underivatized FU.

PMID- 7820188
TI  - [Acrosomal function and male fertility].

PMID- 7820187
TI  - MHC-unrestricted immune surveillance of leukemia.
AB  - The characteristics of natural killer (NK) cells and their role in
      immunosurveillance of cancer is reviewed. Evidence derived from in vitro and in
      vivo experiments is in favor of an important role of NK cells in host resistance
      to leukemia, as illustrated by studies of untreated patients, patients treated
      with biological response modifiers and by bone marrow transplantation.

PMID- 7820189
TI  - [Techniques and indications for using an endoscopic sac in the management of
      ovarian cysts].

PMID- 7820190
TI  - [3D echography in gynecology and obstetrics. State of the art].

PMID- 7820191
TI  - [Ovulation inhibition with medrogestone administered on the 4th through the 24th
      day of the cycle].
AB  - Medrogestone (M) is a derivative of 17 methylprogesterone (P) used for P
      insufficiency at oral doses of 5 to 15 mg/day (D). We studied the ability of M to
      inhibit cyclic pituitary-ovarian activity when given at a dose of 10 mg/d from D4
      to D24. Ten healthy Caucasian females, aged from 21 to 33, volunteered for an
      open 2 consecutive cycle study (cycle 1 = control, cycle 2 = M). At inclusion
      mean (+/- SD) cycle length was 28.6 +/- 1.9 D. Plasma LH, FSH, E2, P, were
      measured daily from D10 to D20 and at D22, 24, 26. During cycle 1, every subject
      showed an ovulatory pattern with mid cycle E2 peak (151-400 pg/ml), LH peak (12
      59 mUI/ml) and luteal P rise (9.4-22.8 ng/ml). Under M ovulatory surges were
      suppressed in each of the 10 subjects and P remained below 0.8 ng/ml. These data
      show that in addition to its known progestomimetic effect, M is a potent
      ovulation inhibitor when given from D4 to D24 of the cycle.

PMID- 7820192
TI  - [Manic depressive disorder, pregnancy, and psychotropic treatment].
AB  - Several therapeutic problems are posed when a manic-depressive patient is or
      wishes to become pregnant. The relative risks and benefits of psychotropic
      treatments must be carefully assessed. Available data on teratogenic risks and
      neonatal complications (overdosage or withdrawal syndromes) are briefly reviewed.
      Treatment guidelines for pregnant bipolar patients are proposed.

PMID- 7820193
TI  - [Diagnostic and therapeutic value of laparoscopic needle biopsies of persistent
      para-uterine cysts: absence of recurrences and consecutive pregnancies. In view
      of ultrasonography-guided biopsies].
AB  - In the presence of a persistent para-uterine cyst, the actual tendency is to
      operate by laparotomy or most frequently by laparoscopic surgery. This leads to
      ablation of 20% of the so called "Functional cysts". A 30 years experience of
      laparoscopic puncture of 745 persistent para-uterine cysts, among which 321 were
      preserved and controlled, shows that 69% of them, of various origin or nature do
      not recur, whereas many pregnancies happen to come at short notice: 59% of 117
      patients who wished to be pregnant had 73 known living children. Young,
      nulliparous or sterile patients, could at a first step, under strict conditions,
      get the benefit of a sonographic-guided diagnostic and therapeutic puncture,
      avoiding a useless endoscopy or ablation.

PMID- 7820194
TI  - [The major Bartholin vestibular glands and their secretion: anatomy, physical
      properties, and physiological roles].
AB  - The present article summarizes observations and experimental data obtained from
      the major vestibular Bartholin's glands in both human and animals with special
      reference to glandular anatomy as wells as chemical composition, physical
      properties and physiological roles of the vestibular secretion.

PMID- 7820195
TI  - [Female orgasmic nodules].
AB  - During experimental female orgasm (or illation), the prominence of five stages
      which correspond to the orgastic raise. This raise leads to the apparition of
      very characteristic nodules, which are structured as they group desquamed vaginal
      cells together with transuded blood cells. Furthermore, the loss of
      pseudocrystallization of the ovulatory cervical phlegm is to be noted ("fern type
      crystallization"). An enzymatic explanation for these phenomena, which lead to
      the intervention of hyaluronidases, may be proposed.

PMID- 7820196
TI  - Pediatric generalist training: graduate medical education at a crossroads.
AB  - There is a growing consensus that the United States is training more physicians
      than it needs or can afford. Public resources are likely be used to bend the
      graduate medical education enterprise increasingly toward the production of
      generalist physicians to practice primary care. Pediatrics, with its generalist
      tradition, can stand tall at this crossroads if it renews its commitment to
      training high quality generalists and assumes a leadership position as graduate
      medical education moves from the hospital into the community.

PMID- 7820197
TI  - Firearm injuries in children and adolescents: epidemiology and preventive
      approaches.
AB  - Firearm injury, now a leading cause of death in childhood and adolescence, had
      jointed the ranks of pediatric conditions that threaten child health and
      development. This paper reviews articles on epidemiology (of firearm injuries and
      the firearms themselves) and prevention. Epidemiology of injuries: 5356 Americans
      under 20 years of age died of firearm injuries in 1991; most of these were
      homicides, and most involved 15 to 19 years olds. The same year, firearm deaths
      exceeded motor vehicle deaths in seven states and the District of Columbia. Case
      control studies showed that handguns in the home raised the risk of homicide
      threefold, and that handguns raised the risk of suicide ninefold; for suicide,
      the risk was greatest (13-fold) in those without psychiatric problems. In Iowa,
      handguns were used disproportionately often in suicides (as compared with other
      firearms). Hospitalized pediatric shooting victims often had social as well as
      medical problems. Epidemiology of firearms: gun ownership was higher among
      incarcerated youths than in community controls (83% vs 22%), but the patterns of
      gun acquisition were similar: mainly handguns for self-protection, most often
      from a friend or family member, or "off the street," cost under $100 per gun.
      Among 5000 families attending pediatric offices, 32% owned handguns or rifles;
      13% of handguns and 1% of rifles were stored unlocked and loaded. In a school
      survey, three-fourths of first and second graders who knew there was a gun at
      home knew where it was. Gun sales are very loosely under the jurisdiction of the
      Bureau of Alcohol, Tobacco, and Firearms; no regulations affect gun design, and
      oversight of commerce is extremely lax.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7820198
TI  - Diagnosis, management, and implications of maternal depression for children and
      pediatricians.
AB  - The past decade has witnessed a marked increase in the quantity and quality of
      research relating to maternal depression and the children of depressed mothers.
      Such children are at heightened psychological risk of problems in adjustment and
      depression. The outcomes in this vulnerable group are determined by many
      influences in the child, the mother, and the family. There is a reciprocal
      relationship between psychological problems in the child and in the mother.
      Recently, the contextual and transactional aspects of maternal depression has
      been emphasized in the literature. Attention has to be given not only to the
      mother and her child but also to acute and chronic family stressors. In this not
      uncommon life event, the pediatrician has a key role in early identification and
      intervention, both preventive and therapeutic.

PMID- 7820199
TI  - Current approaches to measuring health outcomes in pediatric research.
AB  - Because improving health is the ultimate goal of a health care system, the
      measurement of health outcomes in research is a logical and important goal for
      the evaluation of the impact of health services. Although health can be defined
      in various ways, here we employ a conceptualization that has several domains
      including longevity, disease, comfort, perceived well being, activity,
      achievement, and resilience. Given that health is such a broad concept, the
      difficult task for outcomes research is to provide the means of measuring it. As
      this brief summary of current work indicates, a number of approaches have been
      used in recent pediatric studies. Most focus on a small subset of health
      concerns. However, some studies have attempted to broaden the assessment of
      health outcome either by using multiple health measures or developing
      multidimensional instruments for measuring health. Care must be taken in
      evaluating the usefulness of any of the instruments until sufficient data are
      obtained as to their reliability and validity. Further work in this area is
      needed, particularly with regards to multidimensional approaches, which are
      beginning to provide a more sensitive and comprehensive means of assessing the
      impact of health services.

PMID- 7820200
TI  - Informatics and general pediatrics.
AB  - Medical informatics is both a science, which seeks to understand the information
      requirements of medical practice, research, and education, and an engineering
      discipline, which applies new technologies to help manage the explosion of data
      and new knowledge that confront contemporary physicians. Computerization of the
      patient record is expected to resolve long-standing problems with the current
      paper-based system. Medical decision support applications provide patient
      specific advice and remind clinicians about problems that might otherwise be
      overlooked. New methods are required to evaluate the performance of expert
      systems in the medical domain where a single "gold standard" solution may not
      exist. Modern technologies can facilitate communication among multiple providers
      and between clinicians and patients. The need for improvements in user-interface
      design and for standards for recording and interchanging information pose ongoing
      challenges for informatics research.

PMID- 7820201
TI  - Inflammatory bowel disease in children.
AB  - Inflammatory bowel disease in children and adults remains the most challenging
      problem in gastroenterology. There is an increasing body of immunologic and
      genetic evidence to suggest that Crohn's disease and ulcerative colitis are
      different diseases, but that once inflammation begins, many common secondary
      pathways of inflammation are initiated. The major recent conceptual advance is
      the observation that mice in whom different immunoregulatory pathways are
      disrupted develop an inflammatory bowel disease. In the case of interleukin-2
      knockout mice, the lesion restricted to the colon, is virtually identical to
      ulcerative colitis in humans, and is initiated by the normal bacterial flora. Yet
      these mice possess anticolon antibodies, long-considered to be of pathologic
      significance in ulcerative colitis. These animal models will allow detailed
      longitudinal studies to be done, and less reliance will need to be placed on
      cross-sectional studies of chronically inflamed gut from patients.

PMID- 7820202
TI  - Constipation in children.
AB  - Chronic constipation with or without fecal soiling remains an important cause of
      childhood morbidity. A number of articles have appeared in the past year to
      advance our understanding of the pathophysiology, treatment, and long-term
      outcome of functional constipation and to give us a new treatment approach for
      intractable constipation in children. Hirschsprung's disease has been localized
      to chromosome 10. In addition, the number of children with preoperative
      enterocolitis of Hirschsprung's disease has decreased, most likely due to the
      availability of anorectal manometry and better staining methods of the rectal
      biopsies, which has resulted in earlier diagnosis. The mean age at diagnosis
      decreased to 2.6 months. Neuronal intestinal dysplasia does not appear to be a
      unique clinicopathologic entity.

PMID- 7820203
TI  - Lactose intolerance and lactase deficiency in children.
AB  - The term lactase deficiency is widely used to indicate a low or absent level of
      lactase enzyme in the small intestine, leading to lactose intolerance. This term
      is correctly used when the intestinal mucosa is damaged and results in secondary
      lactase deficiency. In the case of the genetically determined decrease of lactase
      activity during childhood, however, low lactase levels suggest that the majority
      of the world's population is "abnormal," whereas individuals from caucasian
      extraction with high levels of lactase enzyme throughout life are then considered
      "normal." It would be better to ascribe racial and ethnic lactose malabsorption
      as the result of genetically determined reduction of lactase activity, rather
      then implying an "abnormality" by the term, "deficiency." Recent studies reveal
      that this genetic control is at the transcriptional level. The symptomatology of
      lactose intolerance varies widely, and the diagnostic method of choice is the
      lactose breath hydrogen test in combination with clinical findings, although
      small intestinal biopsies should be performed when mucosal diseases are
      suspected. Treatment of lactose intolerance depends on the age of the child. In
      young infants complete restriction of lactose containing foods is rarely
      necessary.

PMID- 7820204
TI  - Applications of gastrointestinal endoscopy in infants and children.
AB  - Gastrointestinal endoscopy has become an integral part of defining and treating
      gastrointestinal disease in children. Premalignant conditions that have been
      identified by endoscopy with histologic evaluation include Barrett's esophagus,
      juvenile polyposis coli, generalized juvenile polyposis, familial polyposis,
      Gardner's syndrome, and Turcot's syndrome. Advances in endoscopic instrumentation
      has allowed successful endoscopic retrograde cholangiopancreatography (ERCP) to
      be performed in infants and children. Therapeutic ERCP has been performed to
      remove stones, ligate strictures, and place stents. This review focuses on
      selected advances in gastrointestinal endoscopy and related diseases.

PMID- 7820205
TI  - A 10-day-old boy with direct hyperbilirubinemia.

PMID- 7820206
TI  - Therapeutic use of inhaled nitric oxide.
AB  - Nitric oxide is a gaseous endogenous mediator of vascular dilation, neural
      transmission, defense against microorganisms, and inhibitor of platelet adhesion.
      Endothelium-derived nitric oxide is important in the maintenance of normal
      vascular tone in the systemic and pulmonary circulation. The discovery of a
      selective pulmonary vasodilator has eluded investigators for many years. Inhaled
      nitric oxide can be used to selectively manipulate the pulmonary vasculature and
      represents an important advance in pharmacologic strategies aimed at the
      treatment of the diseased pulmonary circulation. Indeed, preliminary studies of
      the therapeutic use of inhaled nitric oxide in human pulmonary hypertension and
      respiratory failure are yielding encouraging and exciting results. Controlled and
      randomized studies will be required to show improvement in patient outcome and
      the absence of adverse sequelae from inhaled nitric oxide therapy.

PMID- 7820207
TI  - Fetal and pediatric origins of adult cardiovascular disease.
AB  - Adult-onset cardiovascular disease has its origin in childhood. During the past
      year there have been a number of articles that have dealt with the effects of
      fetal nutrition on the development of cardiovascular disease in adult life,
      identification of the child at high risk for the development of essential
      hypertension, the effects of passive smoking as a risk factor for coronary artery
      disease, and strategies for diagnosis and treatment for familial
      hypercholesterolemia. Two of the most important observations over the past year
      are that there appears to be a significant relationship between fetal and early
      childhood nutrition and the risk of developing many of the cardiovascular
      diseases seen in adult individuals and that environmental tobacco smoking,
      including smoke at work, results in an increased risk of developing coronary
      heart disease.

PMID- 7820208
TI  - Ventricular septal defect and left sided obstructive lesions in infants.
AB  - Infants born with ventricular septal defect and left sided obstructive lesions
      display a variety of pathophysiologic features. Some patients have relatively
      straightforward afterload- or preload-induced congestive heart failure, whereas
      others have a mixed pattern. The presence of patent ductus arteriosus may add to
      the left-to-right shunt, or when the physiology is that of preductal coarctation,
      may be associated with a small left ventricular chamber. Over the years, various
      management schemes have been devised for infants with ventricular septal defect
      and left sided obstructive lesions. These have continued to evolve as surgical
      skills and techniques have improved for the neonate. However, differences among
      medical centers remain in 1994 regarding the type and timing of various one- and
      two-stage repairs. Ventricular septal defect and coarctation or interrupted
      aortic arch, especially when associated with other types of left ventricular
      outflow obstruction remains a serious high-risk problem, but affected infants
      appear to have a better long-term prognosis today than in the past. Complete
      repair at the time of diagnosis in the neonate, regardless of whether associated
      obstructions are present, remains the gold standard. However, excellent results
      can be obtained by more conservative approaches to these lesions, especially if
      the ventricular septal defect is not unduly large. For patients with ventricular
      septal defect and mitral stenosis, a series of palliative procedures and
      operations are often required.

PMID- 7820209
TI  - Management strategy in neonates presenting with pulmonary atresia with intact
      ventricular septum.
AB  - The management of neonates with pulmonary atresia and intact ventricular septum
      presents a challenging problem mainly because of the profound heterogeneity of
      the morphology of the right ventricle. This article outlines a different approach
      to the management based on the presence or absence of a well-formed infundibulum
      (outflow) of the right ventricle. In most of the children with a well-formed
      infundibulum, successful biventricular repair can be achieved, after promoting
      the growth of the right ventricle by promoting ategrade flow through it. In
      patients with poorly formed or an absent infundibulum, on the other hand, a
      Fontan procedure is an excellent solution.

PMID- 7820210
TI  - Atopic disease, rhinitis and conjunctivitis, upper respiratory tract infections,
      and insect stings and snake bites.
AB  - In this section we review four broad topics in pediatrics: atopic disease,
      rhinitis and conjunctivitis, upper respiratory tract infections, and insect
      stings and snake bites. The first three topics comprise three of the most
      commonly encountered problems in pediatric practice. Although the fourth topic
      accounts for a relatively small number of office visits, it generates a great
      deal of concern among our patients and their parents. There have been significant
      contributions to the pediatric literature in each of these areas over the past
      year and we review those of particular interest here. The papers that we have
      chosen to review were selected for both their scientific significance and
      practicality. Both review articles and original research are included, but all
      should be relevant to the care of your patients.

PMID- 7820211
TI  - Prenatal diagnosis and treatment of congenital adrenal hyperplasia.
AB  - Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is
      associated with hormonal imbalance which predisposes affected females to prenatal
      development of genital ambiguity. Because the disease is usually not lethal and
      can be treated with glucocorticoids, affected pregnancies are seldom terminated.
      Dexamethasone can be administered to the pregnant mother and is effective in
      correcting the fetus's adrenal hormone imbalance during gestation. Nearly a
      decade's experience with prenatal treatment of CAH indicates that the risk
      benefit ratio is favorable for mother and fetus with careful medical supervision
      of gestationally administered dexamethasone.

PMID- 7820212
TI  - Prenatal diagnosis and treatment of congenital adrenal hyperplasia.
AB  - Advances in technology have made possible the prenatal diagnosis and treatment of
      female fetuses with classical congenital adrenal hyperplasia due to 21
      hydroxylase deficiency. Hormonal measurement of 17-hydroxyprogesterone,
      androstenedione, testosterone and 21-deoxycortisol and HLA typing and DNA
      analysis for 21-OH/C4/HLA class I and II genes in chorionic villus cells and
      amniocytes are utilized for prenatal diagnosis. Maternal dexamethasone
      administration begun in the first trimester has prevented or ameliorated
      virilization in approximately three-fourths of infants. Maternal estriol levels
      appear to be the most accurate measure of fetal adrenal suppression. Maternal
      side effects are not infrequent and include excess weight gain, edema, glucose
      intolerance, hypertension and gastrointestinal problems. Severe permanent striae
      have been reported. Although no complications of prenatal treatment in the
      treated fetus or child have been reported long-term follow-up with careful
      neuropsychologic evaluation is not yet available and is necessary to fully
      evaluate possible long-term side-effects of prenatal dexamethasone treatment.

PMID- 7820213
TI  - Thyroid function in children with perinatally acquired antibodies to human
      immunodeficiency virus.
AB  - We measured T4, T3, TSH, and TBG in 53 children (both asymptomatic and
      symptomatic) with human immunodeficiency virus (HIV) antibodies, and 17 controls.
      Although most had normal T3 and T4 levels, two children with acquired immuno
      deficiency syndrome (AIDS), who were very ill when studied, had low T3 values.
      TBG and TSH levels were higher in children with AIDS than in other HIV-infected
      children or controls (P < 0.005). Increased TSH levels were found in 5 children
      with AIDS who were recovering from severe illnesses. TSH levels returned to
      normal without treatment. In summary: 1) the pattern of thyroid abnormalities in
      children with AIDS was different from that seen in healthy controls, critically
      ill children, other HIV-infected children, and HIV-infected adults; 2) if an
      increased TSH is found, measurement should be repeated before instituting
      thyroxine therapy; 3) an increased TBG is not seen in HIV-infected children until
      clinically evident AIDS is present.

PMID- 7820214
TI  - Decreased T3 and T4 levels following topical application of povidone-iodine in
      premature neonates.
AB  - Thyroid function and iodine levels of 30 preterm neonates were examined before
      and up to five days after topical exposure to 10% povidone-iodine application.
      Urinary iodine excretion significantly increased in the group closest to term
      (8.9 +/- 1.2 mg I/g creatinine x 10) vs controls (3.5 +/- 0.5 mg; p < 0.01). T3
      levels significantly decreased at all sub-group gestational ages vs controls (p <
      0.01-0.05). Similarly, both FT4 and TT4 levels were lower in the subgroups vs
      controls (p < 0.01-0.05). TSH levels however did not rise in any group. These
      data suggest partial failure of thyroid hormone synthesis, in a population of
      high-risk infants possibly already exhibiting features of the euthyroid-sick
      syndrome. Topical iodine-containing antiseptic solutions should be used with
      caution in this population since these antiseptics may modify serum thyroid
      hormone concentrations rapidly.

PMID- 7820215
TI  - Growth follow-up in 100 children with congenital hypothyroidism before and during
      treatment.
AB  - In order to assess the influence of age at onset of treatment on subsequent
      growth, height, weight, head circumference (HC) and bone age as estimated by
      Greulich-Pyle and TW2-RUS methods, 100 children with congenital hypothyroidism
      (CH) were studied before and during adequate treatment up to 5 years of age. The
      patients were divided into five groups according to age at the start of
      treatment: Group 1: < 2 months (n = 26); Group 2: 2-3 months (n = 13); Group 3: 3
      6 months (n = 21); Group 4: 6-12 months (n = 20); Group 5: 12-24 months (n = 20).
      Before treatment, groups 1 and 2 differed significantly from the others in height
      (p < 0.001). With hormone therapy, catch-up growth was observed in groups 3 to 5,
      but at age 5 years no differences were found between groups. In all groups,
      height at 5 years of age correlated significantly with children's midparental
      height (p < 0.002). Bone age was initially retarded in groups 3 to 5, but
      approximated the chronological age by age 5 years. Initially, HC was less
      affected than height and remained relatively larger up to age 5 years in all
      groups. These findings show that thyroid hormone replacement in CH as late as 24
      months corrects the short stature and delayed bone age by age 5 years.

PMID- 7820216
TI  - Endocrine studies in children with myelomeningocele.
AB  - Pituitary-hypothalamic abnormalities due to impaired cerebrospinal fluid
      circulation have long been recognized. The aim of this study was to assess
      pituitary, thyroid, adrenal, and gonadal function in 46 prepubertal (22 M and 24
      F) and 10 pubertal (4 M and 6 F) subjects with myelomeningocele (MMC). Basal
      serum levels of FT3, FT4, TSH, PRL, LH, FSH, T or E2, cortisol, 17-OH-P and DHEA
      S were measured by routine radio-immunoassay methods. Twenty-two prepubertal
      patients had a TRH test for TSH and PRL evaluation, and eight underwent a GnRH
      test. Three patients presented with precocious puberty. Six subjects had modest
      elevations of serum TSH together with normal free thyroid hormone levels. In
      three cases, TSH responses to TRH were significantly exaggerated and prolonged:
      in two patients, TSH responses were delayed. The mean basal plasma FSH level in
      females with ventriculo-peritoneal shunt was significantly higher than in
      controls. In six cases FSH responses to GnRH were significantly higher than in
      controls. Both basal and stimulated PRL levels were elevated in patients with
      shunts; in patients without shunts, basal PRL was normal, but peak PRL levels
      following TRH stimulation were elevated. Our data show an abnormal hypothalamic
      pituitary function in MMC subjects. These findings reinforce the importance of
      physical examination, hormonal evaluation and follow-up of pubertal development
      in patients with myelomeningocele.

PMID- 7820217
TI  - Abnormal alpha cell hypoglycemic recognition in children with insulin dependent
      diabetes mellitus (IDDM).
AB  - Children with IDDM have diminished glucagon responses to hypoglycemia. We
      evaluated possible mechanisms in 60 children and adolescents with IDDM (age 15.4
      +/- 2.6 years, duration 7.8 +/- 3.5 years [mean +/- SD]) and without diabetic
      complications. These were: 1) suppression by hyperinsulinism, 2) autonomic
      neuropathy, 3) a pan-islet cell defect, and 4) a glucotoxic effect. Glucagon and
      pancreatic polypeptide responses to hypoglycemia (insulin bolus 0.15-0.75 U/kg)
      were studied after insulin withdrawal and 3 days of intensive insulin therapy.
      Responses to arginine and mixed meal were also studied. The control group
      consisted of children with non-growth hormone deficient short stature. IDDM
      children had lower glucagon responses to hypoglycemia than controls (p < 0.001),
      the response to arginine did not differ from controls, and was greater than the
      response to hypoglycemia (p < 0.001). Responses to hypoglycemia after insulin
      withdrawal and intensive therapy did not differ. Basal pancreatic polypeptide
      levels were lower in IDDM than in controls (p < 0.05) but responses to
      hypoglycemia did not differ between groups. Thus the diminished glucagon response
      to hypoglycemia reflects a defect in hypoglycemic recognition or response by the
      alpha cells.

PMID- 7820219
TI  - Growth hormone (GH) and the immune system: impaired phagocytic function in
      children with idiopathic GH deficiency is corrected by treatment with
      biosynthetic GH.
AB  - Thirty-seven prepubertal children evaluated for severe growth retardation were
      studied by assessment of total granulocyte, monocyte and lymphocyte count,
      lymphocyte subsets CD3+, CD3+Dr+, CD3+Dr-, CD4+, CD8+, CD8+CD57+, CD8+CD57-,
      CD16+, CD20+ and CD23+, serum immunoglobulin concentrations, and phagocytic
      activity of circulating neutrophils and monocytes (by a flow cytometric assay).
      Idiopathic GH deficiency was diagnosed in 21 of 37 patients; the remaining 16
      healthy subjects served as controls. Fourteen patients received biosynthetic GH
      (rhGH), and their immune parameters were assessed at baseline and after 6 months
      of therapy. Phagocytic function mediated by both polymorphonuclears and monocytes
      was significantly impaired in GH-deficient subjects compared to controls (p <
      0.003 for neutrophils, p < 0.007 for monocytes), while a significant increase of
      phagocytic activity was obtained during long-term rhGH replacement therapy (p <
      0.02 for neutrophils, p < 0.001 for monocytes), thus suggesting that GH may
      affect the functional activity of circulating phagocyte cells. No significant
      differences were found in total granulocyte, monocyte and lymphocyte counts, T-
      and B-lymphocyte subsets and immunoglobulin levels, between GH-deficient patients
      and controls, and between values observed before and during rhGH substitution
      treatment.

PMID- 7820218
TI  - Impaired counterregulatory hormone responses to hypoglycemia in children and
      adolescents with new onset IDDM.
AB  - Children with long-standing IDDM have impaired counterregulatory responses to
      hypoglycemia. To determine whether children with new onset IDDM also have altered
      counterregulation, we studied the counterregulatory responses to hypoglycemia in
      twenty children with new onset IDDM (5-6 days, age 12.6 +/- 2.9 yr, mean +/- SD),
      and compared these responses to 47 subjects with long-standing IDDM (duration 7.8
      +/- 3.6 yr, age 15.3 +/- 2.5 yr) and 21 controls (age 14.2 +/- 2.8 yr). Six new
      onset subjects were restudied three months later during their remission. Glucose
      nadir in new onset (2.7 +/- 0.1 mmol.l-1) was similar to controls (2.4 +/- 0.1
      mmol.l-1), but was higher than in long-standing IDDM (2.2 +/- 0.1 mmol.l-1). Both
      groups of diabetic subjects had lower glucagon responses to hypoglycemia than
      controls (p < 0.005). Glucagon responses in new and long-standing diabetes did
      not differ. Epinephrine was diminished in new IDDM compared to controls (p <
      0.01). Glucose recovery was faster in new onset than in long-standing IDDM (p <
      0.001) and the same as in controls. Responses remained diminished 3 months after
      diagnosis despite increased C-peptide and lower glycosylated hemoglobin. Thus,
      children with IDDM have diminished counterregulatory responses to hypoglycemia at
      diagnosis, that are similar to those in long-standing IDDM. The reasons for this
      impairment and its clinical application in childhood require further
      investigation.

PMID- 7820221
TI  - Clinical and/or biochemical pancreatitis in diabetic ketoacidosis.
AB  - The association between diabetic ketoacidosis and acute pancreatitis is examined
      with reference to four patients. Hypertriglyceridemia was noted in only one of
      the patients. The pancreatitis was relatively mild and resolved rapidly.

PMID- 7820222
TI  - Gonadotrophin-independent precocious puberty and dyschondrosteosis.
AB  - We present a case of gonadotrophin-independent precocious puberty, as seen in
      McCune-Albright syndrome, and Leri-Weill dyschondrosteosis in a six and a half
      year-old girl. Her father also reports having early puberty and is similarly
      affected with dyschondrosteosis. This combination of features has not been
      reported previously, and represents the association of a skeletal dysplasia with
      an endocrinopathy.

PMID- 7820223
TI  - Adult height exceeding target height in a patient with congenital
      panhypopituitarism diagnosed after the age of 25 years.
AB  - This case report concerns a prepubertal patient (height 148.7 cm) with congenital
      anterior panhypopituitarism diagnosed at the chronological age of 25.2 years
      (bone age 12.5). In spite of his advanced age on initiation of hormonal
      replacement therapy this patient achieved an adult height (172.8 cm), exceeding
      those of his father and brothers, because of his markedly delayed bone age. This
      satisfactory height outcome confirms that final height in hypopituitarism depends
      on both height at onset of puberty and height with respect to bone age but not
      chronological age at initiation of growth hormone treatment.

PMID- 7820220
TI  - Neonatal sex-steroid hormones and physical size at four years.
AB  - This study investigated the relationships of neonatal sex-steroid hormones to
      preschool children's size. Two measures of size were considered: a unidimensional
      measure of height and a weight-for-height ratio. Results showed a significant
      positive relationship between girls' neonatal progesterone and the weight-for
      height ratio at age four. A negative association of this ratio with an estrogen
      composite measure was also found. High testosterone girls had higher weight-for
      height ratios than low testosterone girls. A significant positive association
      between the estrogen composite and height was found for boys. These findings
      indicate that neonatal hormone levels are important complements to environmental
      factors (e.g., nutrition) in predicting later growth.

PMID- 7820224
TI  - The illusion of quality in quality management systems: meaningful accreditation.

PMID- 7820225
TI  - Immunohaematology: reminiscences and reflections.

PMID- 7820226
TI  - An assessment of the immunoprecipitation of blood-group antigens using
      biotinylated red cells.
AB  - This study presents a simple protocol for labelling red cell membrane proteins
      and glycoproteins using biotin. The advantages include an increased capacity to
      label and process a large number of cell samples of different phenotypes without
      using large quantities of radionuclides, resulting in no hazardous waste by
      products as in radiolabelling methods, and a fast exposure time for detection of
      the biotinylated component(s). Our assessment on biotinylated red cells was based
      on the retention of antigenic activity with 14 antibodies (13 monoclonals, one
      polyclonal), which have specificities for extracellular and cytoplasmic domains
      of various membrane components, by ELISA, haemagglutination tests and
      immunoprecipitation. A luminescent method was used to detect the
      immunoprecipitates on nitrocellulose membrane after SDS-polyacrylamide gel
      electrophoresis. The development time for band detection was between 5 s and 1
      min. Free amino groups that constitute a part(s) of an antigenic determinant were
      also biotinylated. As a result antibody binding to the red cells was abrogated.

PMID- 7820227
TI  - Identification of recipient Rh phenotype in a chronically transfused child by two
      colour immunofluorescence.
AB  - A child with hyporegenerative anaemia was chronically transfused with group 0 Rh
      negative blood. As typing with anti-D showed a mixed-field pattern, the patient's
      red blood cells (RBC) were identified as D positive. Due to the transfused ccddee
      RBC, it was impossible to determine by simple agglutination whether c was present
      on the patient's RBC. To resolve this question, two-colour indirect
      immunofluorescence was performed using D as a marker of the patient's RBC.
      Likewise, Duffy and Kidd antigens could be determined on the patient's RBC
      despite multiple transfusions.

PMID- 7820228
TI  - Monoclonal antibodies to high-incidence Kell epitopes: characterization and
      application in automated screening of donor samples.
AB  - Monoclonal antibodies, LM313/706 and LM357/828, recognize high-frequency epitopes
      which are absent on red cells of Ko phenotype. Both antibodies have proved
      suitable for automated screening of blood donor samples, with 5 ml of each
      culture supernatant sufficient to screen 3,000 donor samples. In a screen of
      45,545 samples, LM313/706 revealed 11 samples (1:3686) of Kp(a+b-) phenotype.
      Thirty-seven samples of K+k- phenotype were identified in 15,235 samples screened
      with LM357/828 antibody (0.24%). The epitope recognized by LM313/706 was
      inactivated by 2 mM DTT suggesting a possible association with the Jsa/Jsb
      antigen structure. The expression of the k-like epitope detected by LM357/828
      antibody was found to be influenced by pH change.

PMID- 7820229
TI  - Electrokinetic properties of human cryopreserved platelets.
AB  - A method for the cryopreservation of human platelets with glycerol/glucose is
      described which was a simplified modification of the method of Dayian and Pert
      (1979). The effect of cryoinjury of the platelet surface membrane was
      investigated by studying the surface electrokinetic properties of the platelet. A
      significant increase in platelet electrophoretic mobility was found after
      cryopreservation. The fresh platelets had a mean electrophoretic mobility of 1.04
      +/- 0.05 microns s-1 V-1 cm-1 and cryopreserved platelets 1.18 +/- 0.05 microns s
      1 V-1 cm-1, P < 0.05. However, the total platelet sialic acid of fresh platelets
      was 62.5 +/- 5.6 nmol 10(-9) platelets compared to 47.2 +/- 4.6 nmol 10(-9)
      platelets after cryopreservation, P < 0.001. Similarly, the neuraminidase-labile
      sialic acid was 26.4 +/- 4.3 nmol 10(-9) platelets for fresh platelets and 17.6
      +/- 4.0 nmol 10(-9) platelets after cryopreservation, P < 0.001. Using
      polyacrylamide gel electrophoresis with Western blotting, we showed a reduction
      in the platelet glycoprotein Gp Ib after cryopreservation, this was confirmed by
      using crossed immunoelectrophoresis. Electron microscopy revealed a significant
      change in platelet morphology after the cryopreservation procedure with
      disruption of the platelet membrane and also platelet shape change. These
      features may explain the changes in platelet electrokinetic properties.

PMID- 7820230
TI  - Improved strategy for screening prospective blood donors for anaemia.
AB  - Women (568) and men (531) attending blood donation sessions in Wessex in
      September, 1992, were assessed for anaemia by the standard CuSO4 method on finger
      prick (FP) blood samples. The haemoglobin (Hb) concentration on FP samples and on
      venous blood was also checked using the HemoCue. Different FP samples from the
      same donors revealed a wide variation on HemoCue. We recommend retaining the
      CuSO4 method on FP samples as the initial screen, and follow-up of apparent
      failures by determining the Hb concentration on venous sampling with the HemoCue.
      As 54% of females were found on venous samples to be below the current
      recommended threshold (125 g/L) for Hb concentration, we also recommend lowering
      the threshold to 115 g/L for women, and to 130 g/L for men. We further recommend
      a close re-examination of normal haematology values for adults.

PMID- 7820231
TI  - Failure of the revised pre-donation guidelines to prevent people with a history
      of high-risk behaviour from donating blood.
AB  - We have evaluated the effectiveness of the alteration in the literature aimed at
      the self-exclusion of blood donors with a history of high-risk behaviour. Since
      the introduction of anti-HCV screening on 1 September 1991 all HCV-positive
      donors in the Trent Region have been invited for interview by Blood Transfusion
      medical staff to ascertain risk factors for HCV infection. We have compared the 5
      month periods before (1 September, 1992 to 31 January, 1993) and after (1
      February, 1993 to 30 June, 1993) the introduction of the amended literature on 1
      February, 1993. No differences between the two time periods were noted for the
      prevalence rate of HCV infection amongst new or repeat donors, or history of risk
      factors or specific exclusion criteria. The new literature is failing to exclude
      people with a history of high-risk behaviour from donating blood and further
      study of this problem is urgently required.

PMID- 7820232
TI  - Two-years' experience with a Canadian hospital-based autologous blood donor
      programme.
AB  - Two years' experience with a hospital-based autologous blood donor programme is
      described. Of 511 patients enrolled, 86% underwent surgery without use of
      allogeneic blood, and 19% of collected units were not used. For six common
      procedures, a 'target' autologous blood schedule of 2 or 3 units (depending on
      the procedure) was set. If an extra unit for each of 407 patients had been
      collected (i.e. 3 or 4), an additional 20 patients would have been protected from
      exposure to allogeneic blood at a cost of 387 unnecessary collections. The
      difference between the mean haemoglobin (Hb) concentration at entry to the
      programme and the mean pre-operative Hb concentration was not clinically
      important and only 25 of 511 patients were deferred on account of anaemia after
      one or more donations. The autologous blood used represents 3.8% of the units of
      blood or packed red blood cells transfused during the 2 years of study. Adverse
      (vasovagal) reactions were infrequent (2.2%) in spite of liberal acceptance
      criteria.

PMID- 7820233
TI  - Inventory management in Sydney Public Hospital Blood Banks.
AB  - Monitoring the outdating of donated units is one way of assessing the efficiency
      of blood usage. Inventory management in public hospital blood banks in Sydney was
      reviewed with the aim of determining factors which lead to the outdating of donor
      blood. Factors which correlated significantly with increased outdating in
      hospitals included absence of an effective hospital transfusion committee; high
      ratio of average inventory: units transfused; fewer than three routine deliveries
      from the BTS per day; increased time taken for delivery of urgent products; CT
      values greater than 2:1, premature performance of the crossmatch and prolonged
      crossmatching holding time. Hospitals were informed of the initial audit results
      and were alerted to the factors contributing to excessive outdating. They
      received monthly feedback of individual outdating results compared with overall
      outdating. After 6 months there was a significant reduction in overall outdating
      from 5.0 to 0.9% (P < 0.05), which has been maintained for a further 12 months.
      Changes in inventory management associated with an improvement in overall
      outdating included: changes in crossmatching practice which increase the
      effective shelf-life of blood, knowledge of when blood was due to outdate and
      effective stock rotation.

PMID- 7820234
TI  - The low risk of hepatitis C virus transmission among sexual partners of confirmed
      HCV-positive blood donors.

PMID- 7820235
TI  - Transfusion in paroxysmal nocturnal haemoglobinuria: a change of policy.

PMID- 7820236
TI  - Distal chevron osteotomy with lateral release for treatment of hallux valgus
      deformity.
AB  - From 1986 to 1990, 42 feet in 30 patients had a combined chevron osteotomy and
      lateral release to correct their painful bunion deformity. Seventeen patients, 23
      feet, were available for follow-up. The purpose of this study was to evaluate the
      outcome of this procedure and to determine the incidence of avascular necrosis.
      The patients were examined by an independent examiner, radiographs obtained, and
      questionnaires filled out. Avascular necrosis was determined using plain films
      read by a musculoskeletal radiologist who did not know the outcomes. The average
      age was 45 years at the time of the procedure. Average follow-up was 50 months.
      The preoperative intermetatarsal angle averaged 13 degrees and the hallux valgus
      angle averaged 31 degrees. At study follow-up, the intermetatarsal angle averaged
      8 degrees and the hallux valgus angle averaged 17.5 degrees. The results were
      graded by the Mayo Clinic Forefoot Scoring System (75-point scale) and a
      subjective scoring system. Average postoperative Mayo Clinic score was 67.
      Fifteen feet were subjectively rated as excellent, six as good, and two as fair.
      Complications occurred in four feet. Hallux varus occurred in two feet, extension
      contracture in one foot, and an infection in one foot. None of the feet developed
      definite radiographic evidence of avascular necrosis. Distal chevron osteotomy
      combined with a lateral release for corrective bunion surgery has come under
      scrutiny, because of the risk of avascular necrosis of the first metatarsal head.
      However, our study showed no evidence of avascular necrosis on radiographs. In
      addition, 91% of patients had good to excellent results at an average 50-month
      follow-up.

PMID- 7820237
TI  - The effect of hallux sesamoid resection on the effective moment of the flexor
      hallucis brevis.
AB  - In this cadaver study, the functional significance of the hallux sesamoid bones
      was quantified by measuring the effective tendon moment arm (ETMA) of the flexor
      hallucis brevis (FHB) force. (The ETMA differs from the anatomic tendon moment
      arm in that ETMAs are determined by the experimentally measured moment of the
      tendon force, rather than by the actual location and orientation of the tendon
      pull in the joint). The intact case was compared with three levels of progressive
      sesamoid resection: distal half of the medial sesamoid excised, entire medial
      sesamoid excised, and both the medial and lateral sesamoids excised. Five
      dorsiflexion angles of the metatarsophalangeal joint were tested, ranging from 
      10 degrees to 50 degrees. A known active load was applied to the FHB muscle of
      fresh frozen cadaver specimens while the corresponding resisting forces from
      three orthogonally mounted transducers were being recorded. Results showed that
      the ETMAs decreased significantly (P < .05) only with the excision of both
      sesamoids. The percent decrease in ETMA was smallest at dorsiflexion angles of 
      10 degrees and 15 degrees (4.3% and 2.4%, respectively) and largest at
      dorsiflexion angles of 25 degrees, 35 degrees, and 50 degrees (29.2%, 22.4%, and
      26.7%, respectively). The clinical significance of the results is that distal
      hemiresection of the medial sesamoid or full medial sesamoid excision is unlikely
      to appreciably compromise the effective mechanical advantage of the FHB muscle.
      However, this mechanical advantage may be profoundly diminished by excision of
      both hallux sesamoids.

PMID- 7820238
TI  - The ankle joint prosthetic replacement: clinical performance and research
      challenges.
AB  - This article presents an up-to-date summary of ankle joint biomechanics and
      various aspects relevant to the endoprosthetic replacement of this joint
      (specifically, the tibiotalar articulation) when indicated. These aspects are:
      the design requirements, choice of materials, and clinical studies involving
      various designs. The reasons for the disappointing in vivo performance of most
      ankle implants, to date, are suggested and areas for research and development,
      aimed at introducing a new generation of these implants, are identified.

PMID- 7820239
TI  - Gait pattern analysis after ankle ligament reconstruction (modified Evans
      procedure).
AB  - We followed 38 patients with chronic ankle instability treated by a modified
      Evans procedure. Evaluation at an average of 68 months follow-up included a
      standard clinical questionnaire and examination, radiological procedures, and
      gait analysis. Plantar pressure distribution measurements were recorded during
      walking and were compared with data from a group of normal subjects (N = 100).
      The subjective patient questionnaire revealed 87% good or excellent results, but
      residual pain was reported by 40% of the patients. The gait analysis indicated a
      significant increase in midfoot loading (22%) consistent with an observed
      restriction of inversion after surgery. However, the plantar pressure changes
      were not associated with poor clinical outcome. We cannot say whether these
      increased pressures will be associated with long-term outcome.

PMID- 7820240
TI  - Vertical shear fractures of the medial malleolus: a biomechanical study of five
      internal fixation techniques.
AB  - Fifty embalmed human tibias were osteotomized to create a simulated vertical
      shear (supination-adduction) fracture of the medial malleolus and were stabilized
      using one of five internal fixation techniques. In offset axial testing, which
      simulated supination-adduction loading, the fixation strength of tibias
      stabilized with either cortical or cancellous lag screws placed perpendicular to
      the osteotomy was over five times greater than the strength of those treated with
      an antiglide plate and nearly two and a half times greater than those treated
      with cancellous lag screws placed oblique to the osteotomy. The tibias stabilized
      with cancellous lag screws placed perpendicular to the osteotomy exhibited twice
      the fixation strength of the tibias stabilized with an antiglide plate and distal
      lag screw. The tibias stabilized with an antiglide plate and distal lag screw and
      perpendicularly placed cortical or cancellous lag screws demonstrated three times
      greater resistance to displacement to the applied supination-adduction load than
      those stabilized with an antiglide plate alone. In offset transverse testing, to
      simulate loading in external rotation, the mean failure load of the tibias
      stabilized with cancellous lag screws placed perpendicular to the osteotomy was
      over two and a half times greater than those stabilized with an antiglide plate
      and distal lag screw. No significant differences were observed in the resistance
      to displacement for these tests. These results support the use of lag screws
      placed perpendicular to the fracture surface for stabilization of vertical shear
      fractures of the medial malleolus and indicate that the use of an antiglide
      plate, with or without a distal lag screw, does not offer any advantage over lag
      screw fixation.

PMID- 7820241
TI  - The sural nerve in the foot and ankle: an anatomic study with clinical and
      surgical implications.
AB  - Operative procedures and traumatic injuries of the lateral foot and ankle place
      the sural nerve and its branches at risk. Anatomic studies quantifying the course
      of this nerve are sparse. In this study, 17 cadaver specimens were dissected to
      clarify its course and branching patterns. Despite multiple variations of the
      nerve and its branches, description of the course of a "typical" nerve trunk was
      possible. The nerve was found to lie in close proximity to the Achilles tendon at
      a level of 7 cm above the tip of the lateral malleolus. In the hindfoot, the
      nerve coursed 14 mm posterior and 14 mm inferior to the malleolus. Distally, it
      crossed superficial to the peroneus longus and brevis tendons. An anastomotic
      branch coursing into the sinus tarsi area was observed in 24% of specimens. An
      understanding of the course and distribution of the sural nerve may lessen the
      risk of iatrogenic injury.

PMID- 7820242
TI  - The influence of x-ray orientation on the first metatarsocuneiform joint angle.
AB  - The purpose of this study was to determine whether the first metatarsocuneiform
      (MC) joint angle is affected by the orientation of the x-ray beam, whether it can
      be reliably measured, and, therefore, whether it is a valid indication of
      tarsometatarsal fusion as an adjunct to hallux valgus surgery. Each of seven
      cadaver feet were loaded to 350 newtons in a Plexiglas apparatus that maintained
      the foot in a plantigrade position. The loading apparatus was positioned to
      simulate a 10 degrees, 20 degrees, and 30 degrees dorsal angulation of the x-ray
      beam. At each position, simulated weight-bearing radiographs were obtained for
      each foot. Three observers independently measured the first MC angle and the
      first intermetatarsal (IM) angle on all the radiographs. The data collected were
      analyzed by the components of variance. The inclination of the first MC joint
      lessons significantly as the orientation of the x-ray beam changes from a 10
      degrees to a 20 degrees tilt. The three examiners' mean MC angles and mean IM
      angles from the three sets of radiographs were not statistically different from
      each other, implying that there were minimal examiner-to-examiner differences in
      measuring these angles. There were no significant differences in measurements
      between examiners, suggesting that the first MC and first IM angles can be
      measured reliably. There was a significant difference in the first MC angle, with
      different orientations of the foot with respect to the x-ray beam, suggesting
      that this angular measurement should not be used as an indication for
      tarsometatarsal arthrodesis.

PMID- 7820243
TI  - Outpatient foot care: correlation to amputation level.
AB  - A retrospective analysis of Department of Veterans Affairs automated inpatient
      and outpatient records was performed for 3945 patients who underwent lower
      extremity amputation surgery due to peripheral vascular disease during fiscal
      year 1991. Demographic and clinical data were collected from reviewing patient
      database information for all Department of Veterans Affairs Hospitals nationwide.
      Patients were identified from the Physicians' Current Procedural Terminology
      codes for lower extremity amputations, and then divided into three groups (above
      the knee, below the knee, and foot and ankle) based on the most proximal level of
      amputation performed. Results indicate that increased use of designated foot care
      clinics was significantly associated with more distal level amputation surgery.
      Patients with above-the-knee amputations averaged 1.0 foot care clinic visit in
      the 2 years prior to amputation, whereas below-the-knee and foot and ankle
      amputees averaged 2.8 and 5.3 foot care clinic visits, respectively (F[df =
      2,3939] = 94.20, P < .05). The same finding was noted when only users of foot
      care clinics were examined. Patients with a codiagnosis of diabetes were more
      likely to undergo distal amputation than those with other diagnoses (P < .05).
      The results of this study suggest the potential effectiveness of designated foot
      care clinics in preserving limb length in individuals with peripheral vascular
      disease and diabetes.

PMID- 7820244
TI  - A disposable fiberoptic arthroscope: a cadaver study.
AB  - Nine fresh cadaver ankle joints underwent arthroscopy to determine effectiveness
      of a small diameter, disposable, fiberoptic arthroscope. A sequential examination
      of the joint was performed through routine anteromedial and anterolateral
      portals. The anterior aspect of the joint with all anatomical structures was well
      visualized via the two anterior portals. The posterior aspect of the joint was
      also well visualized via anterior portals without distraction due to the
      flexibility of the scope and its small diameter. The quality of the visualization
      of the posterior joint from the anterior portals alone was comparable to that
      from the posterior approach. The results of this study indicate that diagnostic
      arthroscopy of the ankle joint with this disposable 1.6-mm arthroscope is
      comparable to the standard 2.7-mm to 5-mm arthroscopes. The size, flexibility,
      and 30 degrees viewing angle of this scope allow excellent and thorough joint
      visualization by routine anterior portals and minimize the need for joint
      distractors and posterior portals during routine diagnostic ankle arthroscopy.

PMID- 7820245
TI  - Asymmetric bifurcation of the extensor digitorum longus tendon in a case of
      congenital digitus minimus varus.
AB  - Congenital digitus minimus varus (overlapping of the fifth toe) is often
      bilateral and may result from an anatomic deformity of the extensor digitorum
      longus tendon. Although bifurcation of the tendinous slip to the fifth toe has
      been reported as an anatomical variant, in those patients affected with
      overlapping fifth toe, a pronounced asymmetry between the medial and lateral
      components may occur. Not only do the two slips to the fifth toe differ in girth,
      but the morphology of the separate tissues reflects a dissimilar level of
      organization. Surgical techniques for correction of secondary overlap should
      consider the possibility of altered gross and histologic anatomy of the extensor
      tendon when attempting to preserve function.

PMID- 7820246
TI  - Combined rupture of the anterior tibial and posterior tibial tendons: a new
      clinical entity.
AB  - Two patients with combined rupture of the anterior tibial tendon and posterior
      tibial tendon are described. Both were elderly women with a gradually progressive
      valgus deformity of the ankle/hindfoot and severe pain. Arthrodesis procedures
      were performed in both patients; however, postoperative complications prevented
      significant clinical improvement. This combined tendon rupture is presented to
      document a new clinical entity.

PMID- 7820247
TI  - Neglected rupture of the Achilles tendon.
AB  - Delayed treatment of a rupture of the Achilles tendon is a challenge. Operative
      treatment is generally recommended, with a variety of techniques being described
      to appose the tendinous ends and augment the repair.

PMID- 7820248
TI  - Radiographic changes in the first metatarsal head after distal chevron osteotomy
      combined with lateral release through a plantar approach.

PMID- 7820250
TI  - Complementary chromatographic analysis of free diacylglycerols and potential
      glycerophospholipid precursors in human SH-SY5Y neuroblastoma cells following
      incubation with lithium chloride.
AB  - We performed detailed chromatographic analyses on the molecular species of the
      major glycerophospholipids (GPLs) and free sn-1,2-diacylglycerols (DAGs) from SH
      SY5Y human neuroblastoma cells following incubation with or without LiCl. For
      this comparison the inositol, choline, ethanolamine and serine GPLs were
      dephosphorylated with phospholipase C and the released sn-1,2-diacylglycerols
      along with the DAGs were subjected to high-temperature GLC on polar and non-polar
      capillary columns as their trimethylsilyl and tert.-butyl-dimethylsilyl ethers. A
      30-min incubation with 10 mM LiCl increased the total amount of human
      neuroblastoma DAGs by 32-58% (P < 0.05) to 2.6 pmol/micrograms cell protein. This
      was accompanied by a limited qualitative shift in the molecular species pattern,
      the most obvious of which was the increase (13%) in the major saturated
      polyunsaturated molecular species and the ca. 46% increase in the minor 18:1-18:1
      species over control levels. The DAGs originated mainly from the inositol GPLs
      (IGPLs), as indicated by the high levels of the characteristic 18:0-20:4n6 (18:0
      20:3n9) species in both IGPLs and DAGs, and to a lesser extent from the choline
      GPLs (CGPLs), as indicated by the high proportion in CGPLs of the oligoenoic
      species, which were largely absent from IGPLs. Alkenylacylglycerols were not
      detected in DAGs, although they made up some 60% of the total ethanolamine GPLs
      (EGPLs). No significant changes in the molecular species composition of the
      cellular GPLs, including IGPLs, were detected after exposure to LiCl.

PMID- 7820249
TI  - Femtomole detection of amino acids and dipeptides by gas chromatography-negative
      ion chemical ionization mass spectrometry following alkylation with
      pentafluorobenzyl bromide.
AB  - Amino acids and di- and tripeptides were derivatized by extractive alkylation
      using pentafluorobenzyl bromide (PFBBr) followed by reaction with
      heptafluorobutyric anhydride (HFBA) and N,O-bis(trimethylsilyl)trifluoroacetamide
      (BSTFA). Good chromatographic separation and the formation of intense diagnostic
      ions were observed for the derivative when examined using gas chromatography
      negative-ion chemical ionization mass spectrometry (GC-NICI-MS). Of the 20 amino
      acids investigated, only Arg and Glu could not be detected by this method. Also,
      dipeptides which included neutral amino acid residues were derivatized with more
      success than those containing either acidic or basic residues. Each of the amino
      acids or dipeptides formed one major derivative with the exception of Asn which
      formed two derivatives with either one or two HFB groups. This derivatization
      method was optimized with respect to the reaction temperature, reaction time, and
      choice of derivatizing reagents. Recoveries of derivatized [3H]-labeled Phe, Lys,
      and Thr were 76, 55, and 34%, respectively. Linearity was observed from 10 to
      2000 pg of Ala per vial; selected-ion monitoring provided a detection limit of
      less than 150 fg with a signal-to-noise (S/N) ratio of 80 to 1. This method has
      proven to work well with urine samples and shows great promise for the detection
      of small peptides at low levels.

PMID- 7820251
TI  - Quantitation of the fatty acid composition of phosphatidic acid by capillary gas
      chromatography electron-capture detection with picomole sensitivity.
AB  - We describe a relatively simple and sensitive method to measure femtomole amounts
      of phosphatidic acid in cells. Phosphatidic acid was extracted from cells in the
      presence of 1-heptadecanoyl-2-heptadecanoyl-sn-glycero-3-phosphate as an internal
      standard, purified by two-dimensional thin-layer chromatography, and hydrolyzed
      to its constituent free fatty acids which were then derivatized to the
      corresponding pentafluorobenzyl esters. Pentafluorobenzyl esters of fatty acids
      were analyzed by gas chromatography with electron-capture detection. Long-chain
      fatty acids were resolved with excellent signal-to-noise ratios. Using
      heptadecanoic acid as an internal standard for quantitation, as little as 1 fmol
      of pentafluorobenzyl ester of stearic acid was detected with a linear response up
      to 10 pmol. Linear detector responses were obtained for all major classes of
      fatty acids. For phosphatidic acid measurement, the detection limit was at least
      50 fmol thus achieving a 1000-fold increase in sensitivity compared to the most
      sensitive of the previously described methods. An example is provided of
      quantitating phosphatidic acid from minute amounts of biological samples such as
      islets of Langerhans.

PMID- 7820252
TI  - Gas chromatographic profiling and determination of urinary acylcarnitines.
AB  - A method is described for the routine profiling and determination in urine of
      most of the acylcarnitines clinically relevant for the diagnosis of organic
      acidurias. The procedure, which does not require expensive apparatus, involves
      extraction of the acylcarnitines on strong cation-exchange disposable columns,
      mild alkaline hydrolysis and gas chromatography of the liberated monocarboxylic
      acids. The different steps were optimized in order to increase the analytical
      performance. No significant interferences were encountered, the limit of
      detection (signal-to-noise ratio = 3:1) ranged from 0.1 to 4 mg/l and the between
      day coefficient of variation from 3.6 to 17.7%, depending on the acyl species.
      The rapidity of the method results from the application of a single solid-phase
      extraction on disposable columns. The acyl moieties are chromatographed
      underivatized in order to permit the identification of short-, medium- and long
      chain acylcarnitines. The method was assessed by analysing fourteen urine
      specimens from patients presenting an organic aciduria.

PMID- 7820253
TI  - Polymeric 6-aminoquinoline, an activated carbamate reagent for derivatization of
      amines and amino acids by high-performance liquid chromatography.
AB  - A new polymeric reagent containing the 6-aminoquinoline (6-AQ) tag was developed
      and applied for the off-line derivatization of amines and amino acids in high
      performance liquid chromatography (HPLC). The synthesis and characterization of
      this polymeric reagent are described. An authentic external standard of a typical
      amine was synthesized and characterized for the determination of the
      derivatization efficiency. All amines had a derivatization efficiency higher than
      50%; the derivatization of amino acids was performed under optimized phase
      transfer catalysis reaction conditions. Derivatized amines and amino acids were
      separated under conventional reversed-phase conditions and determined by UV and
      FL detectors. To investigate the practical applications, this polymeric reagent
      was also used to derivatize protein hydrolysates.

PMID- 7820254
TI  - Simultaneous determination of leukotrienes B4 and E4 in whole blood and of
      leukotriene E4 in urine of rabbit by reversed-phase high-performance liquid
      chromatography.
AB  - Sulfidopeptide leukotrienes E4 (LTE4) and B4 (LTB4) were simultaneously extracted
      from rabbit whole blood with acetonitrile. LTC4 and LTD4 were converted to LTE4
      by gamma-glutamyl transpeptidase and leucine-amino peptidase before extraction.
      LTE4 was extracted from urine with C18 Sep-Pak cartridges. The compounds were
      resolved and quantitated by reversed-phase high-performance liquid chromatography
      (HPLC) with a diode-array detector; in selected cases the collected fractions
      were assayed for LTB4 and LTE4 by specific enzyme immunoassay (EIA). The
      correlation factor of the measured increase in LTE4 concentrations and addition
      of incremental amounts of LTC4 to blood was r = 0.998; slope of 1.05 +/- 0.01
      (mean +/- S.D.). Concentrations of LTE4 measured by HPLC correlated with those
      obtained with EIA (r = 0.996; slope = 0.98 +/- 0.03 and r = 0.991; slope = 0.97
      +/- 0.04 in blood and urine, respectively). For blood LTB4 the correlation of
      HPLC versus EIA was r = 0.990; slope = 1.12 +/- 0.04. The method described is
      accurate and reproducible, allowing measurement of both LTB4 and LTE4 in whole
      blood after a single extraction procedure. Simultaneous measurement of these
      metabolites after specific stimulation or in pathological conditions is
      recommended for in vivo investigations of LTs production.

PMID- 7820255
TI  - Quantitation of polymerase chain reaction products by capillary electrophoresis
      using laser fluorescence.
AB  - In samples where the amount of DNA is limited, the polymerase chain reaction
      (PCR) can amplify specific regions of the DNA. A quantitative analysis of the PCR
      product would be desirable to ensure sufficient DNA is available for analysis. In
      this study, we examine the use of capillary electrophoresis (CE) with laser
      fluorescence detection for quantitation of PCR products. A coated open tubular
      capillary was used with a non-gel sieving buffer and a fluorescent intercalating
      dye to obtain results within 20 minutes. Using an internal standard, peak
      migration time was below 0.1% relative standard deviation (R.S.D.) with a peak
      area precision of 3% R.S.D. In comparison to quantitation by hybridization,
      (i.e., slot blot) and spectrophotometric analysis, capillary electrophoresis
      shows distinct advantages due to its ability to separate unincorporated primers
      and PCR byproducts from the targeted PCR product. The results demonstrate that CE
      can be used to monitor the quality and quantity of the PCR product.

PMID- 7820256
TI  - Picogram determination of finasteride in human plasma and semen by high
      performance liquid chromatography with atmospheric-pressure chemical-ionization
      tandem mass spectrometry.
AB  - A method based on high-performance liquid chromatography (HPLC) with atmospheric
      pressure positive-ion chemical ionization (APCI)-tandem mass spectrometric (MS
      MS) detection for the determination of finasteride (MK-906, I) in human plasma
      and semen has been developed. The drug and internal standard (II) were extracted
      from biological matrices using a single solid-phase cyano cartridge. The eluent
      from the cartridge was injected directly onto the a 33 x 4.6 mm I.D. C18, 3
      microns column coupled with a base deactivated C18 20 x 4.6 mm I.D., 5-microns
      guard column. The column eluate was passed into the corona discharge APCI source
      by means of a heated nebulizer interface. The analyte and its internal standard
      were detected using multiple reaction monitoring (MRM) mode for enhanced
      selectivity and sensitivity. The chromatographic run time was 3 min, and the
      method had sufficient sensitivity, precision, accuracy and selectivity for the
      analysis of clinical samples containing finasteride at concentration of 0.2
      ng/ml. The assay methodology confirms the versatility of APCI-MS-MS detection,
      combined with HPLC, for the quantitation of selected drugs in the sub-ng/ml range
      in biological fluids.

PMID- 7820257
TI  - Quantitative measurement of a new synthetic hetrazepine derivative, BN50730, in
      human plasma and urine by combined liquid chromatography-negative chemical
      ionization mass spectrometry using a particle beam interface.
AB  - A new simple and sensitive assay has been developed for the quantitative
      measurement of BN50730 at the picomole level in human plasma and urine. The drug
      and the internal standard (BN50765) were measured by combined liquid
      chromatography-negative chemical ionization mass spectrometry with methane as the
      reagent gas. A simple solid-liquid extraction procedure was used to isolate
      BN50730 from complex biological matrices. Mild operating conditions were required
      to assay the parent drug with a particle beam interface from Hewlett-Packard. The
      mass spectrometer was tuned to monitor the intense ion m/z 333, which was
      generated in the ion source by a dissociative capture process. This assay was
      performed with 1 ml of plasma or 0.1 ml of urine, and the quantification limit of
      the method was statistically calculated as 1 ng ml-1. The very low relative
      standard deviation and mean percentage of error calculated during the different
      within-day or between-day repeatability assays clearly demonstrate the ruggedness
      of the technique for the routine determination of BN50730 in the biological
      fluids. Some preliminary results on the pharmacokinetics of the drug are
      presented to illustrate the applicability of this new powerful LC-MS method.

PMID- 7820258
TI  - High-performance liquid chromatographic determination of spironolactone and its
      major metabolite canrenone in urine using ultraviolet detection and column
      switching.
AB  - A rapid and simple column liquid chromatographic method involving a column
      switching system for the determination of spironolactone and its main metabolite
      canrenone in urine is described. Purification and concentration was performed
      using an Hypersil ODS-C18, 30 microns (20 x 2.1 mm I.D.) pre-column. The most
      polar urinary compounds were removed by washing the pre-column with water, and
      the analytes were subsequently switched to a LiChrospher RP C18, 5 microns (125 x
      4 mm I.D.) analytical column and separated by means of an acetonitrile-water
      mobile-phase. Under the proposed conditions, the extraction efficiency was
      approximately 100% over the 0.5-10.0 micrograms/ml concentration range. The
      limits of detection were 20 ng/ml for both compounds. The proposed method has
      been applied to urine samples obtained after the oral administration of
      spironolactone.

PMID- 7820259
TI  - Stability of apomorphine in plasma and its determination by high-performance
      liquid chromatography with electrochemical detection.
AB  - Dilute solutions (50 ng/ml) of apomorphine in plasma are unstable at 37 degrees C
      and pH 7.4. The chemical half-life is only 39 min. Mercaptoethanol (0.01%) is
      effective in stabilizing these samples while sodium metabisulphite (1%), which is
      generally used, is not effective. Biological samples are extracted with diethyl
      ether (recovery 96.5%) and analysed using HPLC with coulometric detection
      (oxidation potential 0.25 V). The stationary phase employed was C18 material (4
      microns) and the mobile phase was phosphate buffer (pH 3)-acetonitrile (70:30,
      v/v). The flow-rate was 1.8 ml/min. This bioanalytical method presents a reliable
      tool for pharmacokinetic studies in man.

PMID- 7820260
TI  - Determination of zuclopenthixol and its main N-dealkylated metabolite in
      biological fluids using high-performance liquid chromatography with post-column
      photochemical derivatization and fluorescence detection.
AB  - A highly sensitive high-performance liquid chromatographic (HPLC) method for the
      assay of cis-(Z)-clopenthixol (zuclopenthixol) in urine and plasma has been
      developed. Following solid-phase extraction, the samples are chromatographed
      using reversed-phase ion-pairing HPLC. After separation, the solutes, having a
      thioxanthene structure, are transformed on-line into thioxanthones in a
      photochemical reactor. The thioxanthones are highly fluorescent compounds, and
      therefore, low detection limits are obtained when using fluorescence detection.
      Detection limits for zuclopenthixol and its N-dealkylated metabolite, in plasma
      as well as in urine, using fluorescence detection with excitation at 260 nm and
      emission at 435 nm, were found to be 0.05 ng/ml and 0.2 ng/ml, respectively. The
      chromatographic system separates the cis-(Z)- and trans-(E)-isomers of
      clopenthixol from its main dealkylated metabolite. Furthermore, the
      chromatographic system is very suitable for study of the photochemical reaction,
      since the chloro-thioxanthone and thioxanthone are well separated from the
      isomers of clopenthixol.

PMID- 7820261
TI  - Isolation, identification and determination of sulfamethoxazole and its known
      metabolites in human plasma and urine by high-performance liquid chromatography.
AB  - From human urine the following metabolites of sulfamethoxazole (S) were isolated
      by preparative HPLC: 5-methylhydroxysulfamethoxazole (SOH), N4-acetyl-5
      methylhydroxysulfamethoxazole (N4SOH) and sulfamethoxazole-N1-glucuronide
      (Sgluc). The compounds were identified by NMR, mass spectrometry, infrared
      spectrometry, hydrolysis by beta-glucuronidase and ratio of capacity factors. The
      analysis of S and the metabolites N4-acetylsulfamethoxazole (N4), SOH, N4
      hydroxysulfamethoxazole (N4OH), N4SOH, and Sgluc in human plasma and urine
      samples was performed with reversed-phase gradient HPLC with UV detection. In
      plasma, S and N4 could be detected in high concentrations, while the other
      metabolites were present in only minute concentrations. In urine, S and the
      metabolites and conjugates were present. The quantitation limit of the compounds
      in plasma are respectively: S and N4 0.10 micrograms/ml; N4SOH 0.13
      micrograms/ml; N4OH 0.18 micrograms/ml; SOH 0.20 micrograms/ml; and Sgluc 0.39
      microgram/ml. In urine the quantitation limits are: N4 and N4OH 1.4
      micrograms/ml; S 1.5 micrograms/ml; N4SOH 1.9 micrograms/ml; SOH 3.5
      micrograms/ml; and Sgluc 4.1 micrograms/ml. The method was applied to studies
      with healthy subjects and HIV positive patients.

PMID- 7820262
TI  - Simultaneous determination of enrofloxacin and its primary metabolite
      ciprofloxacin in bovine milk and plasma by ion-pairing liquid chromatography.
AB  - A simple and sensitive high-performance liquid chromatographic method has been
      developed for the simultaneous determination of enrofloxacin and ciprofloxacin in
      bovine milk and plasma. Sample preparation consisted of mixing equal volumes of
      milk or plasma with acetonitrile-0.1 M sodium hydroxide (1:1, v/v), followed by
      ultrafiltration through 3000 Da molecular mass cut-off filters. Separation of
      these two fluoroquinolones in milk or plasma ultrafiltrate was accomplished by
      ion-pairing liquid chromatography using a reversed-phase analytical column eluted
      with acetonitrile-methanol-water. Ultraviolet absorbance of the column effluent
      was monitored over the 230-350 nm range with a photodiode-array detector (lambda
      max 278 nm). Recoveries of enrofloxacin from bovine milk and plasma were 92-107%
      and 80-84%, respectively. Recoveries of ciprofloxacin from bovine milk and plasma
      were 92-105% and 73-75%, respectively. The limit of detection for the two
      compounds was 5 ng/ml. Enrofloxacin was administered intravenously to a lactating
      cow at a dose of 2.5 mg/kg. Enrofloxacin was detected in milk within 15 min after
      injection and the metabolite ciprofloxacin rapidly appeared in plasma and milk.
      Both enrofloxacin and ciprofloxacin were below the limit of detection (5 ng/ml)
      by 48 h after drug administration.

PMID- 7820263
TI  - Detection and separation of the anthrapyrazole CI-941 and its metabolites in
      serum and urine by high-performance liquid chromatography.
AB  - A high-performance liquid chromatographic method using ion-pairing chromatography
      on reversed-phase C18 material with a mobile phase of acetonitrile-water (19:81,
      v/v) containing 5 mM 1-pentanesulfonic acid was developed for the detection and
      separation of the anthrapyrazole CI-941 (I) and its metabolites. After sample
      clean-up with solid-phase extraction, I and its metabolites were measurable at a
      wavelength of 491 nm. A detection limit of 5 ng/ml was achievable for I. The
      dicarboxylic acid derivative and the isomers of the monocarboxylic acid
      derivative could be separated. Application of the method to a human
      pharmacokinetic study showed two and four metabolites of I in serum and urine
      respectively.

PMID- 7820264
TI  - Determination of methadone and its primary metabolite in human urine by capillary
      electrophoretic techniques.
AB  - Data presented in this paper show that methadone and its primary urinary
      metabolite (M1) can not easily be determined by SDS-based micellar electrokinetic
      chromatography; however, they separate rapidly under cationic capillary zone
      electrophoretic conditions using a borate buffer with a pH of ca. 9. Eight urines
      obtained from individuals undergoing methadone therapy, which tested markedly
      positive for methadone using an enzyme multiplied immunoassay and in which the
      presence of methadone and M1 was also confirmed by GC-MS, have been analyzed.
      Using an extraction procedure with disposable cartridges containing a copolymeric
      sorbent, the presence of methadone and M1 could be confirmed in all urines,
      whereas with direct urine injection, the two compounds could only be determined
      in six urines. Thus, for unambiguous confirmation by capillary electrophoresis,
      extraction of the compounds of interest is preferred. The described assay is
      rapid (with typical run times being less than 6 min), free of interferences from
      coextracting drugs of abuse and/or their major metabolites, and characterized by
      a good reproducibility. After extraction of 5 ml urine, drug concentrations down
      to ca. 20 ng/ml can be monitored unambiguously.

PMID- 7820265
TI  - Determination of plasma fatty acid composition in neonates by gas chromatography.
AB  - Total fatty acids in plasma of neonates have been analysed as their methyl esters
      by gas chromatography. They were separated on a capillary column coated with a SP
      2380 stationary phase. As little as 100 microliters of plasma is used for the
      analysis. The extraction procedure was performed with dichloromethane-methanol
      (2:1) and fatty acids were methylated with boron trifluoride-methanol. The
      quantification of fatty acids is based on an internal standard method. Absolute
      values (micrograms fatty acid per 100 microliters plasma) are given together with
      relative values (%). At a signal-to-noise ratio of 3, the detection limits for
      flame ionisation detection are between 0.08 to 0.51 ng. The high sensitivity and
      precision permits the effective determination of the fatty acids in neonate
      plasma.

PMID- 7820266
TI  - Investigation of meperidine and its metabolites in urine of an addict by gas
      chromatography-flame ionization detection and gas chromatography-mass
      spectrometry.
AB  - A gas chromatographic method with flame ionization detection (FID) for the
      quantitative analysis of meperidine and mass spectrometry (MS) for the
      qualitative analyses of meperidine and its metabolites in urine was established.
      Meperidine, normeperidine and acetyl normeperidine in urine were extracted with
      ether. Free and conjugated meperidinic and normeperidinic acids in urine, which
      are hydrophillic, were hydrolyzed by acid, esterified with methanol and
      derivatized with acetic anhydride. Meperidine and its four metabolites were
      identified by GC-MS. Meperidine was measured by GC-FID during 72 h after
      intramuscular administration of meperidine to an addict.

PMID- 7820268
TI  - Simultaneous determination of antiepileptic drugs and their metabolites,
      including chiral compounds, via beta-cyclodextrin inclusion complexes by a column
      switching chromatographic technique.
AB  - Using beta-cyclodextrin as a mobile-phase additive, a column-switching
      chromatographic system equipped with two 25-mm short ODS cartridge columns and
      two UV detectors was successfully employed for the simultaneous determination of
      some antiepileptic drugs and their metabolites, including chiral compounds, in
      human serum. The compounds examined were phenobarbital, zonisamide, phenytoin and
      its metabolites, S- and R-5-(p-hydroxyphenyl)-5-phenylhydantoin, R- and S
      mephobarbital, carbamazepine and its main metabolites, 10,11-dihydro-10-11
      epoxycarbamazepine and trans-10,11-dihydroxy-10,11-dihydrocarbamazepine (as a
      racemate), and allobarbital (as an internal standard).

PMID- 7820267
TI  - Simultaneous detection of methylphenidate and its main metabolite, ritalinic
      acid, in doping control.
AB  - Two analytical methods for the simultaneous detection in urine of methylphenidate
      and its main metabolite, ritalinic acid, are described. Both procedures are based
      on solid-phase extraction of urine samples on Bond Elut Certify columns, and
      capillary gas chromatographic-mass spectrometric detection of O-trimethylsilyl, N
      trifluoroacetyl derivatives. The former method is used as a general screening
      procedure for the detection of basic polar nitrogen-containing compounds in urine
      such as stimulants, narcotic and adrenergic drugs. The latter procedure is
      proposed as a specific method to confirm methylphenidate ingestion. The two
      methods are sensitive enough to detect methylphenidate and ritalinic acid in
      urine at least for 24 h after administration of a therapeutic dose (20 mg oral
      dose) of methylphenidate.

PMID- 7820269
TI  - Comprehensive assay for pyrazinamide, rifampicin and isoniazid with its hydrazine
      metabolites in human plasma by column liquid chromatography.
AB  - A comprehensive assay for determination of pyrazinamide (PZA), rifampicin (RIF),
      isoniazid (INH) and hydrazine metabolites is described. The method involves
      organic solvent extraction of PZA and RIF, followed by derivatization of INH,
      monoacetylhydrazine (mHYD) and hydrazine (HYD) with salicylaldehyde and
      extraction with diethyl ether. Acetylisoniazid (acINH) and diacetylhydrazine
      (dHYD) were hydrolyzed to INH and mHYD, respectively, and processed as above.
      Using a gradient solvent programmer, PZA and RIF were analyzed on a C8 (5
      microns) column at 248 nm, while INH and metabolites were analyzed on a C18 (5
      microns) ODS2 column at 280 nm.

PMID- 7820270
TI  - Purity control of different bee venom melittin preparations by capillary zone
      electrophoresis.
AB  - A rapid capillary zone electrophoresis method was developed for the determination
      of melittin during its purification from bee venom by column chromatography. Low
      pH buffer was selected to decrease the adsorption of the analytes on capillary
      wall. The average relative standard deviations of the migration time of melittin
      and of the peak area were 1.2 and 2.3%, respectively.

PMID- 7820271
TI  - General strategies and selection of derivatization reactions for liquid
      chromatography and capillary electrophoresis.
AB  - The general strategies, reasons and the different possibilities for the
      derivatization of biomedically important compounds are reviewed. Different
      approaches apply for small versus large analyte molecules, different advantages
      and disadvantages are visualized with pre- and post-column arrangements.
      Particular interest is focused upon solid-phase derivatization reagents.

PMID- 7820272
TI  - Chiral derivatizing reagents for drug enantiomers bearing hydroxyl groups.
AB  - This review extensively summarizes and critically evaluates the recent research
      on the indirect resolution technique for enantiomeric alcohols. Twenty-one chiral
      derivatizing reagents divided in seven types, including chiral acids, activated
      acids, chloroformates, isocyanates, carbonyl nitriles, oxazolidin-2-ones and
      lactones, are described. The derivatization methods of the various chiral
      reagents, the liquid chromatography separation systems, the detection systems
      used for the diastereomeric derivatives of alcohols as well as their limitations
      and the prospects of the indirect resolution technique for the future are
      thoroughly discussed. This paper aims to instruct the application of a particular
      chiral reagent and the technical approach to be used and should be beneficial to
      the development of an indirect resolution method for enantiomeric alcohols as
      well as to the biomedical investigation of the differences between the antipodes
      of chiral alcohols.

PMID- 7820273
TI  - Derivatization reactions for the determination of aflatoxins by liquid
      chromatography with fluorescence detection.
AB  - Various derivatization methods for the fluorometric detection of aflatoxins after
      separation by HPLC are reviewed. In normal-phase chromatography the sensitivity
      for aflatoxins B1 and B2 was improved by using special mobile phases or a flow
      cell packed with silica-gel particles. In the nowadays more popular reversed
      phase methods, the fluorescence intensity of B1 and G1 can be increased by
      precolumn derivatization with trifluoroacetic acid or by postcolumn
      derivatization with iodine or bromine. Optimum conditions for the reactions are
      discussed. In terms of sensitivity, the three derivatization schemes give similar
      results. The methods are compared with respect to experimental convenience,
      selectivity, reproducibility and suitability for automation.

PMID- 7820274
TI  - Labeling of free carboxyl groups.
AB  - The latest trends in the labeling of free carboxyl groups for high-performance
      liquid chromatography are reviewed. The labeling reagents for fluorescence
      detection are mainly discussed according to their reaction type (or functional
      group). Attention is also paid to the reagents used for ultraviolet detection and
      for enantiomeric separation. The reactivity and sensitivity of the reagents used
      for the labeling of carboxylic acids are described.

PMID- 7820275
TI  - Derivatization reactions for neurotransmitters and their automation.
AB  - Many reagents suitable for the derivatization of neurotransmitters are selective
      for the amino function. Others, however, are selective for the carboxyl-, thiol-
      and hydroxyl function, and recently, reagents selective for more than one
      function have been produced. Interest persists in the established reagents, with
      their well understood behaviour which assists automation of analysis as much as
      new technology. Workers appear reluctant to tackle the optimization of many novel
      reagents. Chiral reagents may become important if d-amino acids are shown to be
      significant from a physiological point of view. Solid-phase reagents offer better
      regulated chemistry and combined derivatization/solid-phase extraction, which
      make them an exciting prospect.

PMID- 7820276
TI  - Derivatization of posttranslationally modified amino acids.
AB  - After a brief overview of posttranslational modifications of protein amino acids,
      the use of various derivatizing reagents for amino acid analysis is discussed.
      Derivatization and chromatographic separation of hydroxyproline, methylhistidine,
      and phosphorylated amino acids are discussed in detail to illustrate some of the
      strategies that can be applied to the analysis of posttranslationally modified
      amino acids.

PMID- 7820277
TI  - Solid-phase derivatization reactions for biomedical liquid chromatography.
AB  - Polymeric reagents have been developed for performing off- and on-line
      derivatizations of numerous organic analytes in HPLC-detection modes. Such
      reagents utilize ionic or covalent attachment of labile tags that possess
      specific detector enhancement properties: ultraviolet, electrochemical,
      fluorescence, and so forth. Specific synthetic procedures have evolved to
      generate various linkages of the tag to the underlying, polymeric support,
      usually involving activated ester connections (leashes). The polymer itself may
      play a number of roles in the nature of the overall reactions, such as
      hydrophobic-hydrophillic exclusion, pore size restriction, stabilization of the
      attachment leashes, and protection of the tags from hydrolysis in aqueous media.
      The basic, underlying chemistry of polymeric reagents has evolved to the point
      where it is possible to engineer the polymer support itself, the attachment
      leash, and the various tags that are then transferred to the analyte molecules.
      These procedures have now reached the stage of commercialization and practical
      applicability for real-world drugs and bioorganics in complex biofluid type
      samples. Polymer supported reagents can now be used for direct injection of
      biofluids with solid-phase (hydrophobic) extraction of the analytes of interest,
      followed by sample cleanup, derivatization, elution onto the HPLC column, peak
      compression, gradient HPLC elution, multiple detection, and final data
      interpretation with quantitation. This review summarizes much or most of what has
      been described in the scientific literature over the past decade in the various
      areas where polymeric reagents are being used for derivatization in HPLC and in
      capillary electrophoresis as well.

PMID- 7820279
TI  - Derivatization of thiol-containing compounds.
AB  - The determination of thiol-containing compounds in biological fluids is important
      in biochemistry and clinical chemistry. In this paper, derivatization reagents
      for thiols are reviewed with respect to their reactivity, selectivity,
      spectroscopic characteristics and their applicability especially to high
      performance liquid chromatography. Derivatization used in ultraviolet and
      electrochemical detection. The derivatization reagents contain a functional
      group, e.g. an N-substituted maleimide, active halogen or aziridine, which react
      with the thiol group. Derivatization for use in flow injection analysis, thin
      layer chromatography or gas chromatography-mass spectrometry is also described.

PMID- 7820278
TI  - Determination of enzyme activity by high-performance liquid chromatography.
AB  - The application of high-performance liquid chromatography (HPLC) in the study of
      enzymatic reactions is reviewed. The rationale for using HPLC is given and
      whether the components of the reaction mixture should be derivatized prior to or
      after HPLC. An alphabetical list of enzymes assayed by HPLC is given. Substrate
      and product are included as well the derivatization reagent, detection method and
      biological matrix. Specific examples of these assays in a complex biological
      matrix viz. faeces are given. Future prospects are the detection of new enzymes
      using synthetic substrates and implementation of mass spectrometry to elucidate
      enzyme specificities.

PMID- 7820280
TI  - Derivatization reactions applicable to pesticide determination by high
      performance liquid chromatography.
AB  - The literature dealing with HPLC analytical methods for pesticides employing
      derivatization reactions is reviewed. Included are methods for insecticides,
      acaricides, nematicides, antimicrobials, herbicides and a rodenticide.
      Derivatization reactions are employed mainly for the purpose of increasing
      sensitivity or selectivity for the UV or, more frequently, fluorescence
      detectors. Of the pre-column and post-column derivatization methods reviewed,
      post-column methods are the more commonly used.

PMID- 7820281
TI  - Enantiomeric derivatization for biomedical chromatography.
AB  - Derivatization reactions aimed at creating the basis for the chromatographic
      resolution of biologically and pharmaceutically important enantiomers are
      reviewed, with emphasis on the literature published in the last 10 years. Three
      main aspects of chiral derivatization are discussed. (a) Enantiomers containing
      suitable functional groups (amino, carboxyl, hydroxyl, epoxy, etc.) are
      transformed into covalently bonded diastereomeric derivatives using homochiral
      derivatizing agents. The diastereomers formed (esters, amides, urethanes, urea
      and thiourea, etc., derivatives) can be separated on achiral stationary phases.
      The derivatization reactions often afford further advantages, such as the
      improvement of chromatographic properties and the detectability of the solutes
      using UV and fluorimetric detectors. (b) Covalent but achiral derivatization is
      often necessary even with the use of chiral stationary phases enabling in
      principle direct enantioseparations (Pirkle-type columns, cyclodextrin-bonded
      phases, glycoprotein column and functionalized cellulose columns). The main goals
      of these derivatization reactions (which are analogous to those discussed above),
      are to introduce functional groups into the molecule of the enantiomers that
      improve the possibilities for chiral interactions or block functional groups to
      avoid non-specific interactions. (c) In the broader sense, the dynamic formation
      of diastereomers using chiral mobile phase additives (cyclodextrins, various
      reagents to form diastereomeric ion pairs, adducts, mixed metal complexes) can
      also be considered to be chiral derivatization reactions and is therefore briefly
      discussed also.

PMID- 7820282
TI  - Fluorogenic reactions for biomedical chromatography.
AB  - A number of fluorogenic reactions, which have been used for HPLC detection
      systems by means of pre- and/or postcolumn derivatization, are surveyed with
      respect to both sensitivity and selectivity for the determination of biomedically
      important substances. For the derivatization of the substances, two types of
      fluorogenic reactions, fluorescence-generating and fluorescence-tagging, have
      been studied. The former are usable in most instances for both pre- and
      postcolumn derivatization methods, and the latter only for precolumn
      derivatization methods. HPLC methods utilizing the fluorogenic reactions allow
      analytes to be detected at picomole-subfemtomole levels. In the fluorescence
      generating reactions, several fluorogenic reagents possessing two or more
      reactive sites in the molecule, which show molecular recognition for a variety of
      analytes, permit facile and reproducible detection in HPLC because there are
      fewer interferences from biological matrices.

PMID- 7820283
TI  - The SecY protein family: comparative analysis and phylogenetic relationships.
AB  - We have cloned and sequenced the plastome encoded secY homologue of the
      cryptomonad alga Pyrenomonas salina. In this study we have carried out a
      comparative analysis of all but one fully sequenced proteins of the SecY family.
      We present an alignment of 16 SecY family proteins, containing family signatures,
      putative transmembrane domains, consensus sequence, and conservation grade. A
      phylogenetic tree derived from the conserved blocks of the alignment reveals the
      relationships among this protein family. The tree shows division into two broad
      subfamilies, one consisting of prokaryotic and plastidal sequences and the other
      of eukaryotic as well as archaeal sequences.

PMID- 7820284
TI  - Phylogeny of the steroid receptor superfamily.
AB  - The phylogenetic relationships of 56 nuclear hormone receptors from both
      invertebrates and vertebrates were determined by the parsimony method (PAUP). The
      consensus tree suggests that the ancestral gene diverged into five major
      subfamilies, each of which evolved into at least one cluster of related
      molecules. These subfamilies are represented by: (1) thyroid hormone receptors
      (TR); (ii) steroid receptors (SR); (iii) retinoic acid receptors (RAR), retinoid
      X receptors (RXR), and the chicken ovalbumin upstream promoter transcription
      factor 1 (COUP) group; (ix) peroxisome proliferator-activated receptors (PPAR);
      and (v) vitamin D receptor (VDR) and knirps (kni) group. Although the neighbor
      joining (N-J) method clustered the receptors into a greater number of
      subfamilies, it was evident that the components of the terminal receptor
      subgroups were similar to those found in the PAUP tree. These terminal clusters
      might then represent phylogenetically stable relationships. The positions of some
      orphan receptors were perturbed when a different algorithm was employed in the
      analysis. Both PAUP and N-J evolutionary trees showed that the receptors within
      the subgroups of a major sublineage tend to recognize hormones of very similar
      structure. This finding suggests that the relative phylogenetic position of
      orphans to well-characterized receptors might be exploited to predict the type of
      ligand they would recognize.

PMID- 7820285
TI  - Molecular systematics of hystricognath rodents: evidence from the mitochondrial
      12S rRNA gene.
AB  - Nucleotide sequence variation among 22 representatives of 14 families of
      hystricognathid rodents was examined using an 814-bp region of the mitochondrial
      12S ribosomal RNA (rRNA) gene composing domains I-III. The purpose of this study
      was twofold. First, the phylogenetic relationships among Old World phiomorph
      (primarily African) and New World caviomorph (primarily South American) families
      were investigated, with a special emphasis on testing hypotheses pertaining to
      the origin of New World families and the identification of major monophyletic
      groups. Second, divergence times derived from molecular data were compared to
      those suggested by the fossil record. The resultant 12S rRNA gene phylogeny,
      analyzed separately and in combination with other morphological and molecular
      data, supported a monophyletic Caviomorpha. This finding is counter to the idea
      of a multiple origin for the South American families. The most strongly supported
      relationships within the Caviomorpha were a monophyletic Octodontoidea
      (containing five families) and the placement of New World porcupines (family
      Erethizontidae) as the most divergent family. Although comparisons to other data
      were more equivocal, the most parsimonious 12S rRNA trees also supported a
      monophyletic Phiomorpha that could be subdivided into two major groups, a clade
      containing the Thryonomyoidea (Thryonomyidae and Petromuridae) plus Bathyergidae
      and the more divergent Hystricidae (Old World porcupines). No significant
      differences in rates of 12S rRNA gene divergence were observed for
      hystricognathids in comparison to other rodent groups. Although time since
      divergence estimates were influenced by the fossil dates chosen to calibrate
      absolute rates, the overall divergence times derived from both transversions only
      and Kimura corrected distances and calibrations using two independent dates
      revealed a divergence time between Old and New World groups dating in the Eocene.

PMID- 7820286
TI  - Molecular phylogenetics of cupped oysters based on partial 28S rRNA gene
      sequences.
AB  - Partial sequences of 28S-like rDNA were amplified using PCR and sequenced for
      eight species of oyster and one species of mussel. Phylogenetic relationships
      among seven species of Crassostreinid oyster were inferred from aligned sequences
      by parsimony and maximum-likelihood methods. Of the 315 sites that varied, 90
      were phylogenetically informative in parsimony analysis. Inference by maximum
      parsimony (MP) is consistent with maximum-likelihood (ML) analysis for the major
      lineages, yielding a tree with the topology (Mytilus edulis (Ostrea edulis
      ((Crassostrea rivularis (C. belcheri, C. gigas))(C. virginica, C. rhizophorae,
      Saccostrea cuccullata, S. commercialis)))). MP and ML analyses resolved the
      systematic relationships of the Saccostrea and Atlantic Crassostrea differently
      such that a polytomy linking these four taxa is preferred with the data
      available. Molecular data support a later divergence of the tropical Pacific
      Saccostrea from a common ancestor of the Atlantic Crassostrea species. Molecular
      data from domains D1, D2, and partial D3 of the 28S rDNA supply sufficient
      phylogenetic information to determine systematic relationships among the extant
      oyster taxa, from the major species groups to the family level, thus providing
      valuable characters that are able to supplement the paucity of morphological
      characters so far recognized.

PMID- 7820287
TI  - Variance to mean ratio, R(t), for poisson processes on phylogenetic trees.
AB  - The ratio of expected variance to mean, R(t), of numbers of DNA base
      substitutions for contemporary sequences related by a "star" phylogeny is widely
      seen as a measure of the adherence of the sequences' evolution to a Poisson
      process with a molecular clock, as predicted by the "neutral theory" of molecular
      evolution under certain conditions. A number of estimators of R(t) have been
      proposed, all predicted to have mean 1 and distributions based on the chi 2.
      Various genes have previously been analyzed and found to have values of R(t) far
      in excess of 1, calling into question important aspects of the neutral theory. In
      this paper, I use Monte Carlo simulation to show that the previously suggested
      means and distributions of estimators of R(t) are highly inaccurate. The analysis
      is applied to star phylogenies and to general phylogenetic trees, and well-known
      gene sequences are reanalyzed. For star phylogenies the results show that
      Kimura's estimators ("The Neutral Theory of Molecular Evolution," Cambridge Univ.
      Press, Cambridge, 1983) are unsatisfactory for statistical testing of R(t), but
      confirm the accuracy of Bulmer's correction factor (Genetics 123: 615-619, 1989).
      For all three nonstar phylogenies studied, attained values of all three
      estimators of R(t), although larger than 1, are within their true confidence
      limits under simple Poisson process models. This shows that lineage effects can
      be responsible for high estimates of R(t), restoring some limited confidence in
      the molecular clock and showing that the distinction between lineage and
      molecular clock effects is vital.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7820288
TI  - DNA-DNA hybridization-based phylogeny for "higher" nonpasserines: reevaluating a
      key portion of the avian family tree.
AB  - A matrix of delta T mode values for 10 birds, including 9 nonpasserines and a
      suboscine passerine flycatcher, was generated by DNA-DNA hybridization. Within
      the most derived lineages, all bootstrapped and jackknifed FITCH trees lend
      strong support to sister-groupings of the two swift families, of hummingbirds to
      swifts, and of these to a clade containing both owls and night-hawks. The
      outgroup duck roots the tree between the woodpecker (Piciformes) and the
      remaining taxa, indicating that Piciformes are among the earliest branches within
      nonpasserines. However, the succeeding branches to kingfisher, mousebird, and
      suboscine passerine flycatcher are based on short internodes that are poorly
      supported by bootstrapping and that give inconsistent results in jackknifing.
      Although these 3 orders may have arisen through rapid or near-simultaneous
      divergence, placement of the "advanced" Passeriformes deep within a more
      "primitive" radiation indicates that nonpasserines are paraphyletic, echoing the
      same distinction for reptiles with respect to their advanced descendants. Despite
      significant rate variation among different taxa, these results largely concur
      with those obtained with the same technique by Sibley and Ahlquist, who used the
      delta T50H measure and UPGMA analysis. This agreement lends credence to some of
      their more controversial claims.

PMID- 7820289
TI  - Jackknifing of weighted trees: validation of phylogenies reconstructed from
      distance matrices.
AB  - The jackknife strict consensus has been used to detect topological
      incompatibilities in phylogenetic trees derived from distance data. We here
      extend this approach to account for branch lengths, as well as topological
      relationships, when comparing jackknife pseudoreplicates. The average consensus
      procedure is used to derive a tree reflecting the agreement among the jackknife
      phylogenies. Combining the average tree with a minimum and a maximum consensus
      provides information about jackknife tree variability; the range consensus
      between the minimum and the maximum represents the topological agreement among
      them. We also demonstrate the effect of the number of pseudoreplicates on the
      resulting consensus trees by considering single and multiple deletions. The
      jackknife extensions that we propose are applied to both hypothetical and DNA-DNA
      hybridization distance data. Consideration of branch lengths reveals greater
      stability of the jackknife phylogeny than would be demonstrated by a strict
      consensus based on topology alone.

PMID- 7820290
TI  - Museum policies concerning specimen loans for molecular systematic research.

PMID- 7820291
TI  - Xantusiid lizards, concern for analysis, and the search for a best estimate of
      phylogeny: further comments.

PMID- 7820292
TI  - On the role of finite mixture models in survival analysis.
AB  - In this paper we review the role of finite mixture models in the field of
      survival analysis. Finite mixture models can be used to analyse failure-time data
      in a variety of situations. In particular, they provide a way of modelling time
      to failure in the case of competing risks.

PMID- 7820293
TI  - Effects of frailty in survival analysis.
AB  - Unobserved individual heterogeneity, also called frailty, is a major concern in
      the application of survival analysis. Hazard rates do not give direct information
      on the change over time in the individual risk, but are strongly influenced by
      selection effects operating in the population. The individuals surviving up to a
      certain time will on average be less frail than the original population. Models
      are reviewed that account for this phenomenon, and some medical examples are
      discussed. It is emphasized that the frailty phenomenon may be modelled in many
      different ways, and a stochastic process approach is discussed as an alternative
      to the common proportional frailty model.

PMID- 7820294
TI  - Some approaches to the analysis of recurrent event data.
AB  - Methodological research in biostatistics has been dominated over the last twenty
      years by further development of Cox's regression model for life tables and of
      Nelder and Wedderburn's formulation of generalized linear models. In both of
      these areas the need to address the problems introduced by subject level
      heterogeneity has provided a major motivation, and the analysis of data
      concerning recurrent events has been widely discussed within both frameworks.
      This paper reviews this work, drawing together the parallel development of
      'marginal' and 'conditional' approaches in survival analysis and in generalized
      linear models. Frailty models are shown to be a special case of a random effects
      generalization of generalized linear models, whereas marginal models for
      multivariate failure time data are more closely related to the generalized
      estimating equation approach to longitudinal generalized linear models.
      Computational methods for inference are discussed, including the Bayesian Markov
      chain Monte Carlo approach.

PMID- 7820295
TI  - Generalizations and applications of frailty models for survival and event data.
AB  - A variety of survival models with both discrete and continuously distributed
      frailty is considered within a framework that involves the specification of three
      sub-models. An intensity sub-model specifies how the intensity is related to
      values of covariates and frailty; a measurement sub-model specifies how fallible
      measures of frailty are related to it; and an exposure sub-model specifies how
      frailty is distributed within the population. The models include those in which
      frailty is due to omitted covariates and those where it represents a covariate
      that has been measured subject to error. Multivariate frailty is also considered,
      with particular emphasis on models suitable for application to genetically
      related individuals, notably twins. A numerical example illustrates the use of a
      model with multivariate frailty for data on repeated exercise times.

PMID- 7820297
TI  - A European School for Cardiovascular Pathology.

PMID- 7820296
TI  - Econometric mixture models and more general models for unobservables in duration
      analysis.
AB  - This paper considers models for unobservables in duration models. It demonstrates
      how cross-section and time-series variation in regressors facilitates
      identification of single-spell, competing risks and multiple spell duration
      models. We also demonstrate the limited value of traditional identification
      studies by considering a case in which a model is identified in the conventional
      sense but cannot be consistently estimated.

PMID- 7820298
TI  - Helicobacter pylori: the new bug on the (paraffin) block.
AB  - A nameless spirillar organism in search of a disease only a few years ago,
      Helicobacter pylori has seen its fortunes suddenly reversed. After a rapid
      succession of name changes and some acrimonious disputes across continents, in
      less than a decade H. pylori has been catapulted to the centre stage of
      gastroenterological and microbiological research and has topped the most-wanted
      list of the pharmaceutical industry. The discovery of H. pylori has provided the
      momentum for the formation of the group that eventually created the Sydney
      System. Today, H. pylori is increasingly recognized as one of the most prevalent
      human pathogens worldwide. Its causal association with chronic active gastritis
      is undisputed and its role in the pathogenesis of peptide ulcer disease, although
      still poorly understood, is universally accepted. Furthermore, possible
      connections between chronic H. pylori infection and gastric carcinoma and primary
      gastric lymphoma are now being explored with increasing alacrity. With a few
      notable exceptions, pathologists have remained passive spectators of these
      exciting discoveries and have allowed gastroenterologists and microbiologists to
      set the pace in the quest for the determinants of gastritis, peptic ulcer and
      gastric cancer. This article is intended to outline some of the accepted facts on
      the development, progression, and pathology of H. pylori gastritis and to pose
      questions about this elusive infection. The authors hope that it might also
      contribute to stimulate further research, particularly on those aspects that are
      eminently suited to be addressed by pathologists.

PMID- 7820299
TI  - Nuclear DNA analysis and prognosis in carcinoma of the thyroid gland. A
      nationwide study in Iceland on carcinomas diagnosed 1955-1990.
AB  - The purpose of this study was to ascertain whether DNA ploidy status and S-phase
      fraction affected the prognosis of patients with carcinoma of the thyroid gland.
      We reviewed all malignant thyroid tumours diagnosed in Iceland from 1955 to 1990.
      In all, 494 thyroid carcinomas were diagnosed during that period. By analysing
      tumour material from paraffin blocks by flow cytometry we were able to evaluate
      the ploidy status in 424 tumours and the S-phase value in 417 tumours. We
      detected aneuploid cell populations in 9.7% of papillary carcinomas, 24.3% of
      follicular carcinomas, 42.9% of medullary carcinomas and 78.6% of anaplastic
      carcinomas. Some 57% of tumours, mainly papillary carcinomas, had an S-phase
      value of less then 3%, whereas most of the other histological types of carcinoma,
      including all the anaplastic tumours, had an S-phase value of > or = 3%.
      Univariate analysis indicated that both ploidy status and S-phase fraction were
      significant variables. When taking into account known prognostic variables of
      thyroid carcinoma in a multivariate analysis, however, neither ploidy status nor
      S-phase value proved significant. We conclude that DNA ploidy status and S-phase
      values are not independent prognostic factors in thyroid carcinoma.

PMID- 7820300
TI  - Intraductal papillary-mucinous tumours represent a distinct group of pancreatic
      neoplasms: an investigation of tumour cell differentiation and K-ras, p53 and c
      erbB-2 abnormalities in 26 patients.
AB  - Intraductal papillary growth of mucin producing hypersecreting, columnar cells
      characterizes a group of rare pancreatic exocrine neoplasms which we propose to
      call intraductal papillary-mucinous tumors (IPMT). We analysed the histopathology
      of 26 IPMT in relation to gastro-enteropancreatic marker expression, genetic
      changes and biology. Four IPMT showing only mild dysplasia were considered to be
      adenomas. Nine tumours displayed moderate dysplasia and were regarded as
      borderline. Severe dysplasia-carcinoma in situ changes were found in 13 IPMT
      which were therefore classified as intraductal carcinomas. Six of these
      carcinomas were frankly invasive and two of these had lymph node metastases. The
      invasive component resembled mucinous non-cystic carcinoma in all but one tumour
      which showed a ductal invasion pattern. Immunohistochemically, an intestinal
      marker type was found in most carcinomas, while gastric type differentiation
      prevailed among adenomas or borderline tumours. K-ras mutations (seven at codon
      12 and one at codon 13) were found in 31% of IPMT (2 adenomas, 1 borderline, 5
      carcinomas). Nuclear p53 overexpression was detected in 31% of IPMT (6 carcinomas
      and 2 borderline IPMT) and correlated with p53 mutations (one at exon 8 and the
      other at exon 5) in two carcinomas. p53 abnormalities were unrelated to K-ras
      mutation. c-erbB-2 overexpression was observed in 65% of IPMT, with various
      grades of dysplasia. Twenty-two of 24 patients are alive and well after a mean
      post-operative follow-up of 41 months. Only two patients, both with invasive
      cancer at the time of surgery, died of tumour disease. It is concluded that
      pancreatic IPMT encompass neoplasms which, in general, have a favorable
      prognosis, but are heterogeneous in regard to grade of dysplasia and marker
      expression. Adenoma, borderline tumour, intraductal carcinoma and invasive
      carcinoma can be differentiated. p53 changes but not K-ras mutation or c-erbB-2
      overexpression are related to the grade of malignancy. Most IPMT differ in
      histological structure, marker expression and behaviour from ductal
      adenocarcinoma.

PMID- 7820301
TI  - Ambient pressure stimulates immortalized human aortic endothelial cells to
      increase DNA synthesis and matrix metalloproteinase 1 (tissue collagenase)
      production.
AB  - In the present study, we investigated the effect of ambient pressure on [3H]
      thymidine incorporation and on the production of matrix metalloproteinase 1
      (tissue collagenase/proMMP-1) using human aortic endothelial cells immortalized
      with simian virus 40 (SE-1). Incubation of cells at ambient pressures of 50 and
      100 mmHg for 24 h slightly increased [3H]-thymidine incorporation when directly
      compared with normal culture conditions. The amount of [3H]-thymidine
      incorporated in SE-1 reached a maximum at 150 mmHg, while a further increase in
      pressure to 200 mmHg decreased incorporation. The same ambient pressure slightly
      stimulated human aortic intimal smooth muscle cells (SMC) to increase [3H]
      thymidine incorporation but not medial SMC. Immunoblot analysis also showed that
      ambient pressure, ranging from 50 to 200 mmHg, like 12-O-tetradecanoyl-phorbol-13
      acetate stimulated SE-1 to produce proMMP-1, an effect not seen with either
      intimal or medial SMC. The amount of proMMP-1 produced also reached a maximum
      level at 150 mmHg. We postulate that human endothelial cells are ambient pressure
      sensitive and that relatively lower ambient pressures play an important role in
      the growth of endothelial cells, while higher pressures injure endothelial cells,
      resulting in the initiation of atherosclerosis. This cell line may prove useful
      in the investigation of both the physiological and pathological roles of blood
      pressure on endothelial cell function.

PMID- 7820302
TI  - Gene expression of CD24 core polypeptide molecule in normal rat tissues and human
      tumor cell lines.
AB  - CD24 antigen is a glycoprotein expressed on haematopoietic cells, including B
      cells, T cells and granulocytes and on non-haematopoietic cells, including neural
      cells, ganglion cells and the cells of the adrenal medulla. The antigen is also
      expressed on renal cell carcinoma, small cell lung carcinoma and neuroblastoma.
      We have cloned rat cDNA encoding core polypeptide of CD24 antigen from embryonic
      brain and shown that the core molecule is highly expressed in embryonic brain and
      non-neural tissues. Rat tissue and various human neoplastic cell lines were
      investigated for the gene expression of CD24 core polypeptide by in situ
      hybridization. The transcript was localized in gastrointestinal epithelia, ductal
      and acinar epithelia of the salivary gland, the bronchiolar epithelium, renal
      tubular epithelium, the epithelium of the oviduct, follicular cells of the
      thyroid, medullary cells of the adrenal gland, Auerbach's plexus, B blastoid
      cells in lymph nodes, hair follicles, and the sweat glands of the skin. Among the
      various human neoplastic cell lines investigated, the transcript was detected in
      squamous cell carcinoma of the lung, gastric carcinoma, colon carcinoma,
      choriocarcinoma and renal cell carcinoma. The result suggest that the core
      molecule of CD24 antigen may be expressed in a wider range of epithelial cells
      and carcinoma cell lines than has been reported. Furthermore, we show that gene
      expression of CD24 core polypeptide is confined to the proliferative zone of the
      gastrointestinal mucosa, suggesting that core molecule is transiently expressed
      on the surface of epithelial cells in the process of cellular maturation. We
      discuss a possible role for CD24 antigen in the maturation of epithelial cells in
      the gastrointestinal tract.

PMID- 7820303
TI  - Sequential changes in intercellular junctions between hepatocytes during the
      course of acute liver injury and restoration after thioacetamide treatment.
AB  - Sequential changes of gap junctions (GJs), tight junctions (TJs) and desmosomes
      (DSs) between hepatocytes during restorative proliferation were studied in rats
      after a single intraperitoneal administration of 200 mg/kg thioacetamide (TAA).
      Antibody against connexin 32 was used to demonstrate GJs; simultaneously the
      changes in TJs and DSs were studied using antibodies against 7H6 protein and
      desmoplakins. Propidium iodide and bromodeoxyuridine were used to recognize
      necrotic and proliferative cells. GJs were evenly distributed in early necrotic
      hepatocytes at 16 h after TAA treatment, then disappeared from necrotic and
      surrounding cells at 24 h. At 48 h, GJs had disappeared completely from
      hepatocytes in whole liver lobules, while many hepatocytes were heavily labelled
      with BrdU. At 72 h, GJs reappeared, firstly in perinecrotic areas. At 96 h after
      treatment, when the injured areas had disappeared and restorative proliferation
      ceased, GJs were distributed evenly throughout the lobules. Immunohistochemical
      observation of GJs in centrilobular, perinecrotic and periportal areas after TAA
      induced hepatic necrosis was confirmed by counting the number of connexin-32
      positive spots in the respective areas. TJs and DSs disappeared from necrotic
      cells at 24 h, but then increased between 24 and 48 h in perinecrotic areas,
      though the increased intensity of these junctions was more evident at 48 h. At 72
      h, localization of TJs and DSs returned to normal. These results suggest that
      during the course of acute hepatic injury, GJs (cell-cell communication) behave
      differently from other intercellular junctions.

PMID- 7820305
TI  - Low oxygen and glucose improves the development of fertilized bovine oocytes in
      defined medium without somatic cells.

PMID- 7820304
TI  - X-ray microanalysis of rat mast cells stimulated with compound 48/80 in
      combination with quick-freezing method.
AB  - X-ray microanalysis was performed on rat mast cells prepared by quick-freezing,
      cryosectioning and freeze-drying (QF-FD) method, or quick-freezing and freeze
      substitution (QF-FS) method. Peritoneal cells including mast cells were
      stimulated with compound 48/80 for 0, 10 or 30 s at 17 degrees C, and the mast
      cells stimulated for 30 s started exocytosis. In X-ray spectra of the QF-FD
      specimen, mast cells stimulated for 10 s increased their levels of phosphorus,
      sodium and chlorine in the intergranular cytoplasm prior to exocytosis, and kept
      this increase until 30 s after stimulation. In the QF-FS specimen, where soluble
      elements were removed, peaks of phosphorus, sulphur and potassium could be
      detected as elements in X-ray spectra. Phosphorus increased and potassium
      decreased in intergranular cytoplasm of mast cells stimulated for 10 s, and these
      changes became more obvious after 30 s. However, supplemental increase of other
      cations such as sodium could not be detected in the QF-FS specimens.

PMID- 7820306
TI  - Influence of fatty acids and bovine serum albumin on the growth of human hepatoma
      and immortalized human kidney epithelial cells.
AB  - The protective influence of bovine serum albumin against growth inhibition caused
      by fatty acids was studied in human hepatoma (HepG2) and immortalized human
      kidney epithelial (IHKE) cells. In general, growth inhibition by unsaturated
      fatty acids (0.15 mmol/liter) increased with increasing number of double bonds.
      For HepG2 cells crude albumin (1 g/100 ml) did not greatly modify growth
      inhibition by arachidonic, eicosapentaenoic, and docosahexaenoic acid. With
      oleic, linoleic, and linolenic acids, crude and defatted albumin stimulated cell
      growth. In contrast, for IHKE cells both albumins counteracted growth inhibition
      by unsaturated fatty acids to approximately the same extent. When HepG2 cells
      were cultured in the presence of saturated fatty acids (0.3 mmol/liter), C2, C6,
      and C8 had no or little inhibitory effect. C10 and C12 inhibited cell growth
      appreciably, whereas C14, and especially C16, had poor inhibitory effects. Crude
      albumin counteracted growth inhibition by all these fatty acids. In contrast,
      defatted albumin had little or no effect (except against C10 and C12), and even
      increased the growth inhibition by C14 and C16. With unsaturated fatty acids
      there seemed to be an inverse relationship between cell growth and the
      concentration of thiobarbituric acid reactive substances (TBARS) in media.
      Vitamin E abolished growth inhibition (and the increase in TBARS concentration)
      by unsaturated fatty acids. The complex interaction between fatty acids and
      albumins calls for great caution when interpreting data on growth effects.

PMID- 7820307
TI  - Evaluation of the xenobiotic biotransformation capability of six rodent hepatoma
      cell lines in comparison with rat hepatocytes.
AB  - Phase I and II activities were examined in six rodent hepatoma cell lines and
      compared with those of cultured rat hepatocytes both in basal conditions and
      after exposure to 5 microM methylcholanthrene, 2 mM phenobarbital, and 15 microM
      beta-naphtoflavone. The metabolic profile of testosterone was also studied. The
      highest aryl hydrocarbon hydroxylase and 7-ethoxycoumarin O-deethylase activities
      were found in MH1C1 cells. Comparable values for 7-ethoxyresorufin O-deethylase
      activity, ranging from 21.6 to 42.9 pmol/mg x min, were observed in the
      hepatocytes and hepatoma cells, except the HTC cells. In contrast, only Fao cells
      showed 7-pentoxyresorufin O-depentylase activity at levels similar to those of
      hepatocytes (6.2 +/- 1.0 and 7.4 +/- 1.2 pmol/mg x min, respectively). Rat
      hepatocytes actively hydroxylated p-nitrophenol, but this activity was not
      measurable in hepatoma cells. Glutathione transferase activity was maintained in
      all the hepatoma cell lines at similar levels to those found in hepatocytes (684
      +/- 56 nmol/mg x min). The seven hydroxylated metabolites of testosterone
      produced by cultured hepatocytes were negligible in hepatoma cells. Exposure of
      cells to inducers revealed that aryl hydrocarbon hydroxylase activity was mainly
      increased after treatment with 3-methylcholanthrene and beta-naphtoflavone, and
      the highest values were found in rat hepatocytes followed by MH1C1 and Fao cells.
      3-Methylcholanthrene and naphtoflavone treatment also resulted in a marked
      increase in 7-ethoxyresorufin O-deethylase activity in hepatocytes as well as in
      H4IIC3, McA-Rh7777, MH1C1, and Fao cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7820308
TI  - Growth of brain microvessel endothelial cells on collagen gels: applications to
      the study of blood-brain barrier physiology and CNS inflammation.
AB  - Brain microvessel endothelial cells (BMEC) exhibit the tendency to migrate
      through 3.0-vm pore semipermeable inserts and establish monolayers on both apical
      and basal filter surfaces. This can potentially lead to complications in
      accurately assessing a wide variety of physiologic parameters uniquely associated
      with these cells. To avoid this problem, we have explored growing BMEC on
      Transwell filters coated with hydrated collagen gels. BMEC seeded on such gels
      grow as a monolayer until confluency, but do not invade the subendothelial
      collagen matrix or the underlying support filter. Furthermore, BMEC grown in this
      manner exhibit biochemical, morphologic, and electrophysiologic properties
      reflective of the endothelial cells that comprise the blood-brain barrier in
      vivo. Although the collagen gel acts as an impenetrable barrier to BMEC, and thus
      ensures the growth of only a single layer of cells, it nevertheless can be
      infiltrated by monocytes that have been stimulated by a chemotaxin to undergo
      diapedesis. Thus, growing BMEC on collagen gel-coated Transwells has broad
      applications for the in vitro study of both blood-brain barrier physiology as
      well as the mechanisms underlying central nervous system inflammation.

PMID- 7820310
TI  - Establishment and characterization of immortalized clonal cell lines from fetal
      rat mesencephalic tissue.
AB  - This investigation reports for the first time the establishment of immortalized
      clones of dopamine-producing nerve cells in culture. Freshly prepared single-cell
      suspensions from fetal (12-day-old) rat mesencephalic tissue were transfected
      with plasmid vectors, pSV3neo and pSV5neo, using an electroporation technique.
      Cells were plated in tissue culture dishes which were precoated with a special
      substrate and contained modified MCDB-153 growth medium with 10% heat inactivated
      fetal bovine serum. The immortalized cells were selected by placing the
      transfected cells in a selection medium (modified MCDB-153 containing 400
      micrograms/ml geneticin). The survivors showed the presence of T-antigens and
      were non-tumorigenic. Two cell lines, 1RB3 derived from cells transfected with
      pSV3neo, and 2RB5 derived from cells transfected with pSV5neo revealed only 1 to
      2% tyrosine hydroxylase (TH)-positive cells. Repeated single-cell cloning of
      these cell lines by a standard technique failed to increase the number of TH
      positive cells in any clones. Using three cycles of growth, alternating between
      hormone-supplemented, serum-free medium and serum-containing medium produced a
      cell line (1RB3A) that was very rich in TH-positive cells. The recloning of 1RB3A
      yielded clones some of which contained over 95% TH-positive cells. These cells
      produced homovanillic acid, a metabolite of dopamine, and may be useful not only
      for neural transplant but also for basic neurobiological studies.

PMID- 7820309
TI  - Isolation of a morphologically and functionally distinct smooth muscle cell type
      from the intimal aspect of the normal rat aorta. Evidence for smooth muscle cell
      heterogeneity.
AB  - Recent studies indicate that the neointima of injured rat arteries is composed of
      a subpopulation of smooth muscle cells (SMCs) distinct from medial smooth muscle
      cells. However, SMC diversity in normal adult aorta has remained elusive. This
      study characterizes two morphologically and functionally distinct SMC types
      isolated from different anatomic regions of the normal rat aorta. Rat aortic
      medial smooth muscle cells (MSMCs) were isolated from the media after removal of
      the intimal and adventitial cells. Rat aortic intimal smooth muscle cells (ISMCs)
      were isolated from the intimal aspect of everted rat aortas. The two cell types
      were characterized morphologically and immunohistochemically and were compared
      for their capacity to contract collagen gels in response to endothelin-1. MSMCs
      were spindle-shaped and grew in hills and valleys showing features previously
      described for vascular SMCs. Conversely, ISMCs displayed a polygonal and
      epitheloid shape, grew mainly as a monolayer, and had a higher proliferative
      rate. Both cell types expressed alpha-smooth muscle actin and were negative for
      Factor VIII-RAg. ISMCs produced large amounts of a laminin and type IV collagen
      rich extracellular matrix which had a characteristic pericellular distribution.
      ISMCs, but not MSMCs, rapidly contracted collagen gels in response to endothelin
      1. This study indicates that the normal rat aorta contains two types of SMCs
      located in anatomically distinct regions of the vessel wall. Because of their
      functional characteristics, the SMCs isolated from the intimal aspect of the
      aorta may play an important role in physiologic as well as pathologic conditions.

PMID- 7820311
TI  - Characterization of a fibroblast cell from the urinary bladder wall.
AB  - For the first time we report on the growth, culture, and matrix production
      characteristics of a cell type isolated from the lamina propria of the urinary
      bladder wall. A fibroblastlike cell was identified as distinct from bladder
      detrusor smooth muscle cells and urothelium based on morphology, growth
      characteristics, and immunohistochemical staining. Characterization of
      extracellular matrix synthesis by this cell type using 35S-methionine metabolic
      labeling demonstrated that these cells are capable of secreting components of the
      surrounding connective tissue, including several fibrillar collagens, a basement
      membrane collagen, and fibronectin.

PMID- 7820312
TI  - Adenylate energy charge of rat and human cultured hepatocytes.
AB  - A simple and rapid method for the assay of adenine nucleotides (ATP, ADP, and
      AMP) was established to evaluate the adenylate energy charge
      (ATP+ADP/2)/(ATP+ADP+AMP) of cultured hepatocytes. The effects of inhibitors of
      glycolysis, fatty acid oxidation, or oxidative phosphorylation on the energy
      charge were examined. The energy charges of cultured hepatocytes in rats and
      human were almost identical and were maintained at a high level between 6 and 24
      h after changing the media (rat: 0.908 +/- 0.008 n = 9, human: 0.918 +/- 0.014 n
      = 6, mean +/- SD). Inhibition of glycolysis with sodium fluoride or oxidative
      phosphorylation with antimycin A irreversibly reduced both the adenine nucleotide
      contents and the energy charge. However, the inhibition of fatty acid oxidation
      with 2-tetradecylglycidic acid did not affect the nucleotide contents, and the
      energy charge only decreased transiently to recover within 8 h. When the
      inhibitor of oxidative phosphorylation was removed, the recovery in the energy
      charge preceded the recovery in the adenine nucleotide contents. These findings
      suggest that the adenylate energy charge is a more sensitive measure of the
      changes in energy metabolism than the adenine nucleotide contents. Furthermore,
      energy charge regulates adenine nucleotide contents in cultured hepatocytes. It
      is important to confirm that the high energy charge of the cultured hepatocytes
      is maintained when these cells are used for metabolic studies.

PMID- 7820313
TI  - Constitutive over-expression of transforming growth factor-alpha in rat liver
      epithelial cells leads to increased cell cycling without transformation.
AB  - Over-expression of transforming growth factor-alpha (TGF-alpha) is consistently
      seen in spontaneous transformants of rat liver derived epithelial cells (RLE phi
      13) and has been implicated in the transformation of other cultured cells. We
      have constitutively over-expressed TGF-alpha in RLE phi 13 cells, which are known
      to express epidermal growth factor receptors, to determine if TGF-alpha over
      expression plays a role in transformation or differentiation, or both, of these
      cells. Early passage RLE phi 13 cells were infected with a replication-defective
      murine retrovirus that expresses both the full length coding sequence for human
      TGF-alpha and the neomycin-resistance gene. Integration of the transcriptionally
      active provirus and expression of TGF-alpha mRNA were confirmed. Neither
      morphologic transformation nor molecular evidence for differentiation was noted
      in TGF-alpha-producing clones. However, these clones did exhibit an accelerated
      growth rate, increased expression of several cell cycle related genes including
      mitotic cyclic B1, proliferating cell nuclear antigen, c-myc, and p53 as well as
      increased expression of the preneoplastic marker enzyme, glutathione-S
      transferase. This suggests that over-expression of TGF-alpha results in increased
      cell cycling, and that subsequent events must be necessary for cellular
      transformation or differentiation or both.

PMID- 7820314
TI  - Failure of many new heart-failure drugs: the need for vasoconstrictor rather than
      vasodilator agents?

PMID- 7820315
TI  - Community care and the clinician.

PMID- 7820316
TI  - Phosphate: an abnormal anion?
AB  - In this era of modern medicine it is understandable that medical practitioners
      can lose sight of the more well-established and perhaps less fashionable
      biochemical tests. The determination of plasma phosphate concentration, it could
      be argued, falls into this latter category and is the subject of this review.

PMID- 7820317
TI  - Management of severe cases of paracetamol overdosage.
AB  - Paracetamol overdose is a problem frequently encountered by junior hospital
      doctors. Although the majority of cases are uncomplicated, it is important that
      management guidelines are followed closely to enable the early recognition and
      treatment of the more severely poisoned patients.

PMID- 7820318
TI  - Decision-making in surgery: management of neoplastic colonic polyps.
AB  - The premalignant nature of neoplastic polyps dictates the need for active
      treatment and polyp removal. Practical protocols, based on the likely risk of the
      growth of further polyps, are required for subsequent follow-up.

PMID- 7820319
TI  - Management of post-term pregnancy: to induce or not?
AB  - Perinatal mortality is increased in pregnancies over 42 weeks, but can be reduced
      by the induction of labour. However, clinicians must consult with the patient as
      to whether she would rather experience spontaneous onset of labour or accept this
      increased risk. This article weighs up the important considerations in this
      difficult area.

PMID- 7820320
TI  - Ethical and legal aspects of illustrative clinical recording.
AB  - The rights of patients participating in illustrations for teaching and medical
      publications must always be respected. A contract between patient and clinician
      subsists in written, informed consent procedures, which in turn are enshrined in
      a Confidentiality Code of Practice.

PMID- 7820321
TI  - Psychiatric adjustment in children with chronic physical illness.
AB  - Improved medical treatments for children with chronic illness have resulted in
      better survival rates as well as more morbidity and use of medical resources by
      ill children. Increasingly, interest is being directed at the implications of
      illness for the child's quality of life and psychiatric adjustment.

PMID- 7820322
TI  - On failing to understand informed consent.
AB  - Many doctors view informed consent as merely a medicolegal concept. This article
      points out that other discourses are possible and that patients would benefit if
      doctors were to take a wider view.

PMID- 7820323
TI  - Antithrombotic therapy in stroke prevention.

PMID- 7820325
TI  - Fly Project Orbis.

PMID- 7820324
TI  - Antithrombotic therapy in stroke prevention.

PMID- 7820326
TI  - Drug utilization review on a surgical intensive care unit.
AB  - Drug use reviews (DUR) provide information about drug prescription patterns. At
      the surgical intensive care unit (SICU) of the University Hospital Frankfurt/Main
      we recorded the indication related administration of blood products and
      pharmaceuticals (which were responsible for 60% of the total costs at the SICU in
      the year before) over a 4-month investigation period. Data were recorded and
      analyzed using a notebook-PC. 207 Patients were included, and recorded total
      expenditures came to $551,592. The 10 leading substances, represented by
      antibiotics and blood-products, caused more than 70% of total costs. The usage of
      these high-cost substances and the most expensive complications are identified
      and discussed. We concluded that DURs are useful for obtaining information about
      drug usage patterns and for identifying high cost drugs, which are of economic
      interest. Furthermore, the indications for the application of these substances
      can be identified. Our results suggest, that blood and blood-products should
      always be included in DURs. In our opinion, especially the usage of blood
      products represents a field where considerable cost savings may be expected. As
      certain complications during the postoperative course (e.g. sepsis) may increase
      costs, they should be considered in the reimbursement negotiations between
      hospitals and health insurance.

PMID- 7820327
TI  - Patterns of drug compliance with medications to be taken once and twice daily
      assessed by continuous electronic monitoring in primary care.
AB  - Adherence to drug treatment is difficult to assess in routine medical practice.
      Therefore, electronic compliance monitoring and a new computer software program,
      the PC-RDP (Reader, Display, Printer) system was used. It allows instant
      evaluation of a patient's dosing record, at the patient's return to the practice.
      Compliance was measured in 24 patients on antihypertensive treatment, either
      continuous (n = 8) or newly prescribed treatment (n = 16) in primary care, for a
      total period of 5144 patient days. Fifteen patients received compliance feedback
      by their physician, 9 did not receive feedback. The drugs prescribed were
      triamterene plus hydrochlorothiazide, as a single dose, once daily (QD), and
      nifedipine twice daily (BID). The mean percentages of prescribed doses taken were
      89% (QD) and 88% (BID). Partial compliance was 10 times more often (1243 days)
      than overcompliance (114 days), and days without dosing were observed twice as
      frequently with the QD than the BID regimen. Omissions of doses occurred more
      often on weekends than any other day of the week. With the BID regimen, evening
      doses were omitted twice as often as morning doses. When treatment was initiated,
      compliance was consistently high until the end of the study period, whereas in
      patients on continuous treatment, it decreased over time. Both compliance
      feedback (n = 11/16) and the beginning of treatment may be important factors to
      explain the difference in compliance behavior. An implementation of compliance
      monitoring into practical patient care seems to be feasible and promising.

PMID- 7820328
TI  - Pharmacokinetics of piracetam: a study on the bioavailability with special regard
      to renal and non-renal elimination.
AB  - The basis of this investigation was a trial on the relative bioavailability of a
      recently developed galenic formulation of piracetam. The open, randomized, single
      blind crossover study was performed in 16 healthy male volunteers aged between 20
      and 31 years. Under fasting conditions, they were given a single oral dose of
      1600 mg piracetam either of the test drug or the reference drug. Blood samples
      and urine specimens were collected over 24 hours. The quantitative analysis was
      performed with a high sensitive HPLC-method. The pharmacokinetic analysis was
      carried out with the PC-based program TopFit. An identical bioavailability of the
      test drug was found (AUC0-24, AUC0-infinity, Cmax, by comparison to the reference
      drug. No relevant difference in piracetam excretion between test and reference
      drug was found, however, in contrast to previous references only about two thirds
      of the given oral dose could be detected in the urine after administration. A
      statistically significant difference (p = 0.001) between total clearance and
      renal clearance was observed. Because an incomplete absorption of the drug in the
      upper gastrointestinal tract is excluded, an additional extrarenal pathway of
      piracetam must be discussed; the hypothesis of an exclusive renal elimination of
      this drug should be overruled.

PMID- 7820329
TI  - Pharmacokinetic properties of E3810, a new proton pump inhibitor, in healthy male
      volunteers.
AB  - E3810 is a new H+,K(+)-ATPase inhibitor with a substituted benzimidazole, which
      is under clinical investigation for peptic ulcer treatment in Japan and the USA.
      Three separate studies were conducted to evaluate the safety and to establish the
      pharmacokinetic profile of E3810 after oral administration to healthy male
      subjects. E3810 was administered as: single oral doses (1, 3, 10, 20, 40 and 80
      mg) in fasting conditions, a single oral dose (20 mg) after a meal and repeated
      oral doses (20 and 40 mg) once daily for 7 days. The concentrations of E3810 and
      its metabolites in plasma and urine were determined by HPLC methods with UV
      detection. E3810 was generally well tolerated by all subjects. In the single-dose
      study, Cmax and AUC increased with increasing doses in the dose range examined.
      The mean plasma half-life was about 1.0 hour and was dose-independent. The
      apparent oral clearance of E3810 ranged from 4.37 to 8.40 ml/min/kg. No
      significant deviation from linear pharmacokinetics was observed. Approximately,
      30% of a dose was excreted into the urine as thioether carboxylic acid-E3810 and
      its glucuronide. The mean serum protein binding was 96.3%. No effect of food
      intake on the Cmax and AUC was observed while tmax after a meal was 1.7 hours
      longer than that in the fasting conditions. No appreciable change in drug
      pharmacokinetics was observed during repeated oral dosing of E3810.

PMID- 7820330
TI  - Determination of drug permeability in a flat or distended stirred intestine.
      Prediction of fraction dose absorbed in humans after oral administration.
AB  - Equations published earlier to calculate intestinal permeability (P) from in situ
      or in vivo studies and to predict fraction of dose absorbed (F) after oral
      administration may often be based on some physiologically and pharmacokinetically
      unrealistic assumptions; for example, (a) the intestine behaving like a "fully"
      distended, rigid, cylindrical tube without any intrinsic motility or stirring,
      (b) no accumulation of drug in gut wall or tissue, (c) lack of blood flow effect
      on permeability, (d) lack of back diffusion from absorptive cell to lumen, (e) a
      smooth surface area for absorption, and (f) a well-defined luminal concentration
      profile. An alternative, simple, realistic organ clearance approach is described
      here to re-define and calculate P as apparent absorptive permeability or
      absorptive clearance per unit gross surface area and to predict F based on either
      human or animal data. The approach may prove particularly valuable in view of the
      insignificant impact of "unstirred" water layer on F. The small intestine in
      humans and animals is found to be very flat overall (only about 10 of 30%
      distension in fasting state). The human intestinal luminal flow after normal
      dosing is estimated at about 3 ml/min, sixfold higher than 0.5 ml/min proposed by
      others. The direct consequence of an early assumption that dimensionless P is the
      same between human and rat is pointed out; the permeability coefficient being 7
      10 times higher in rats than in humans, that is, however, not supported by
      experimental data. The apparent success of a widely used approach to estimate F
      based on rat data is rationalized.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7820331
TI  - Transport of various substances through human enamel and dentine.
AB  - The penetration of 14C-labelled alcohols (methanol, ethanol, n-butanol), 14C
      labelled carbonic acids (formic, acidic, propionic, valerianic, octanoic,
      malonic, succinic and lactic acid), 14C-drugs (procain, barbital), and 14C-sugars
      (saccharose, xylose) into about 800 human deciduous or permanent teeth, both
      healthy and carious, was investigated. Dental enamel up to the cemento-enamel
      junction was incubated at a pH-value of 5.0 or 6.8 for 1 or 24 hours. For
      measurement of radioactivity, the dentine of the root was obtained by
      trepanation. Between intact and carious permanent teeth only slight differences
      were observed in case of the diffusion of methanol and ethanol (2% of the
      incubation medium), while n-butanol penetrated the dentine to an extent of 4.2%
      at a pH of 5.0. The monocarbonic acids penetrated the enamel of healthy teeth
      within 24 hours to an extent of 6.6-19.2% of the content of the incubation
      medium, while the dicarbonic (succinic and malonic) acids reached amounts of 3.6
      and 9.2%, and the percentage of lactid acid which penetrated the enamel reached
      2.9%, respectively. Under all conditions tested, saccharose penetration was
      higher in carious than in healthy teeth (3.8 vs 6.5%). The highest uptake was
      found in experiments with barbital; it was more pronounced in deciduous than
      permanent teeth (16.2 vs 12.4%). The data could be of interest in the therapy of
      inflammatory and other processes of the pulp.

PMID- 7820332
TI  - Maternal drug treatment and human milk banking.
AB  - We studied prospectively during one year temporary drug use by mothers donating
      breast milk to assess the problem of drug treatment of donors. Sixty-four of the
      284 mothers (22.5%) had to abstain from donating due to medication. The
      indication was infection in 50/56 treatments (89.3%). Antimicrobial agents were
      prescribed 44/52 times (84.6%). The channelling of milk from mothers in early
      phases of lactation to premature and newborn infants was identified as a special
      risk situation, if mothers on medication are not excluded. The limited number of
      such donors leads to use of milk unpooled or pooled to small volumes with
      increased risk for adverse effects to babies as a consequence. We recommend a
      wash-out period of 5 half-lives of the drug after the last ingested dose. For the
      majority of drugs in this study, with some important exceptions, a wash-out
      period of 1 day was sufficient.

PMID- 7820333
TI  - The influence of gastric pH on the pharmacokinetics of fluconazole: the effect of
      omeprazole.
AB  - AIDS patients may have achlorhydria, a condition that could result in drug
      malabsorption, especially of antifungals. The effect of a reduction in the
      production of gastric acid on the pharmacokinetics of the antimycotic fluconazole
      after a single 100 mg dose was investigated in a randomized two-way crossover
      study with 12 healthy volunteers. Gastric acid production was reduced by
      pretreatment with 20 mg omeprazole/day over a period of 7 days; pH and gastric
      emptying times were measured by a radiotelemetering pH capsule. Omeprazole
      pretreatment significantly raised the median gastric pH (from pH 1.1 to pH 4.7, p
      < 0.0001), but had no significant influence on gastric emptying time of the pH
      capsule (median = 4.3 vs 4.9 hours). The pharmacokinetics of fluconazole were
      unchanged; plasma parameters were Cmax = 2.04 micrograms/ml, tmax = 4.08 h and
      AUC = 98.91 h micrograms/ml after the omeprazole treatment, compared to 2.06
      microliters/ml, 3.92 hours and 97.29 h micrograms/ml, respectively. The median
      bioavailability ratio of fluconazole before and after omeprazole treatment was
      1.00. It is inferred that there is no interference of omeprazole with the plasma
      pharmacokinetics of fluconazole. The findings suggest that changes in gastric pH,
      as in patients with AIDS or those being treated with anti-ulcer drugs, should not
      influence the pharmacokinetics of fluconazole.

PMID- 7820334
TI  - A method for the evaluation of individual bioequivalence.
AB  - A method is presented for the evaluation of individual bioequivalence. The
      approach is simple and effective. It considers two drugs to be inequivalent in
      individuals if their contrast shows larger variation than that observed within
      formulations, which are repeatedly administered to the subjects. The necessary
      information can be obtained in 3- or 4-period crossover trials, in which
      individuals receive not only both drug products but also the replicate
      application of at least one of them. In the implementation of the procedure, it
      is suggested that two drug products could be considered to show individual
      bioequivalence if the upper, one-sided confidence limit for the ratio of
      intraindividual variances estimated between and within formulations does not
      exceed a preset critical value, Fcr. For initial considerations, a confidence
      level of 90% and Fcr = 4.0 are recommended. The intraindividual variances between
      and within formulations can be estimated either by simple, direct calculations or
      by an analysis of variance (ANOVA). The structure of the latter is different from
      that of the ANOVA applied for the assessment of average bioequivalence. Another
      approach assessing individual bioequivalence from an estimated variance component
      is less favoured. Graphical, exploratory analysis of the multiperiod crossover
      trials is recommended and illustrated. The suggested procedures are demonstrated
      on an example evaluating the individual (and average) bioequivalence of
      olsalazine tablets and capsules.

PMID- 7820335
TI  - The cancer control experiment.

PMID- 7820336
TI  - Clinical indications for the radiosurgical treatment of brain tumors.
AB  - Recently there has been an exponential growth in the use of radiosurgery in the
      treatment of brain tumors. Although a place for radiosurgery in the management of
      benign disorders, especially arteriovenous malformations (AVM) is established,
      its role in the treatment of brain tumors continues to be defined. This paper
      reviews the results of recently-published studies of the use of radiosurgery for
      brain metastases, acoustic neuromas, primary brain tumors and tumors at the base
      of skull. An attempt is made to identify a number of clinical questions that need
      to be addressed before radiosurgery can be advocated as the treatment of choice.

PMID- 7820337
TI  - Prevention of weight gain in obese patients who have lost weight.

PMID- 7820338
TI  - The value of bedside examination in an era of high technology--Part 3.

PMID- 7820339
TI  - Diagnosing Marfan syndrome.

PMID- 7820340
TI  - Diagnosis and management of lipid disorders in children.

PMID- 7820341
TI  - Raynaud's phenomenon.

PMID- 7820343
TI  - Contraception for women with congenital heart disease.
AB  - Barrier methods of birth control are less efficacious than other methods but pose
      significantly less risk of systemic complications for women with congenital heart
      disease. These methods require a motivated patient and a cooperative partner.
      Male contraception was not discussed in this article but certainly should be
      considered when counseling a couple. At present, essentially the only permanent
      option for male contraception is a vasectomy, but other methods are under
      investigation. Sterilization is not recommended uniformly in women with
      cardiovascular disease when pregnancy is feasible and not contraindicated. It may
      be considered an option for women with contraindications to pregnancy, but these
      patients may also be at increased risk from the sterilization procedure.

PMID- 7820342
TI  - Percutaneous transluminal coronary angioplasty and coronary artery bypass graft
      surgery in octogenarians: indications and outcome.

PMID- 7820344
TI  - Recognition and management of subarachnoid hemorrhage.
AB  - Aneurysmal SAH is a devastating disease. A missed diagnosis can have unfortunate
      consequences, such as rebleeding, cerebral infarction, and death. Early
      recognition and prompt referral improve the outcome by providing timely surgical
      intervention to prevent rebleeding and aggressive management to prevent or
      minimize the effects of vasospasm. Patients should be managed in a neurological
      intensive care unit experienced with SAH and its complications.

PMID- 7820345
TI  - Guidelines for the management of transient ischemic attacks. Ad Hoc Committee on
      Guidelines for the Management of Transient Ischemic Attacks of the Stroke
      Council, American Heart Association.

PMID- 7820346
TI  - Educational, occupational, and relationship histories of men who were sexually
      and/or physically abused as children.
AB  - Ninety men (mean age 26) at an urban Northeastern university were administered a
      self-report assessment of their early sexual and physical abuse experiences, and
      their educational, occupational, relationship, and substance abuse histories.
      Subjects were classified as sexually abused according to criteria used by Wyatt
      (1985) and Finkelhor (1979). Sixteen men (17.8%) experienced sexual abuse alone,
      22 men (24.4%) physical abuse alone, 15 men (16.7%) both sexual and physical
      abuse, and 37 men (41.1%) were classified as nonabused. Of the 31 men who
      reported sexual abuse, 24 (77.4%) were contact, the rest noncontact. Sexually
      abused men reported significantly greater difficulties than nonabused men at all
      levels of education: grade school, high school and college. They also reported
      more negative job experiences and more negative experiences in relationships.
      Physically abused men showed a similar but less pervasive pattern of
      difficulties. Substance abuse was significantly more prevalent among both
      sexually and physically abused men than among nonabused subjects.

PMID- 7820347
TI  - The psychological impact of sexual abuse: content analysis of interviews with
      male survivors.
AB  - Autobiographical interviews with 26 adult male survivors of childhood sexual
      abuse were audiotaped, transcribed verbatim and content analyzed to identify
      common psychological themes. Approximately equal numbers of men were abused by
      male and female perpetrators, almost half came from disrupted or violent homes
      and a majority had a history of substance abuse. Fifteen psychological themes
      were identified: Anger, Betrayal, Fear, Homosexuality Issues, Helplessness,
      Isolation and Alienation, Legitimacy, Loss, Masculinity Issues, Negative
      Childhood Peer Relations, Negative Schemas about People, Negative Schemas about
      the Self, Problems with Sexuality, Self Blame/Guilt and Shame/Humiliation. The
      themes are discussed and illustrated with examples drawn from the transcripts.

PMID- 7820348
TI  - Traumatic responses among battered women who kill.
AB  - This study compared levels of violence, social support, and post-traumatic stress
      between battered women charged with a violent crime against an abusive partner
      and those seeking help from a mental health clinic. Results indicated that
      forensic battered women were more likely than clinical battered women to report
      experiencing severe violence, including sexual abuse, in their relationships.
      Women in the forensic sample also reported less social support and greater post
      traumatic stress than women in the clinical sample. However, when social support
      and level of violence were accounted for, levels of general post-traumatic stress
      indicators (MMPI-PTSD, CR-PTSD, GSI) were no longer different between groups,
      although levels of specific post-traumatic stress indicators (intrusion,
      avoidance) remained higher for battered women in the forensic sample.
      Implications for understanding battered women's response to violence and their
      post-traumatic reactions to it are discussed.

PMID- 7820349
TI  - A shooting incident in an elementary school: effects of worker stress on public
      safety, mental health, and medical personnel.
AB  - The effects of impact of event and five categories of worker stress were studied
      with 140 police, fire, medical, and mental health personnel who were involved in
      emergency service work following a shooting in an elementary school. A
      questionnaire distributed 6 months after the incident was utilized. Public safety
      personnel reported a recollection of significantly fewer intrusive thoughts than
      medical and mental health professionals immediately following the incident.
      Groups did not differ in intrusive or avoidance scores on the Impact of Event
      Scale 6 months after the event and all groups showed a significant decrease in
      both scores over time. Stepwise linear regression showed that a self-reported
      qualitatively heavy work load predicted intrusiveness and avoidance of thoughts
      both immediately after and at the 6-month anniversary of the incident.
      Additionally, time pressure and quantitatively heavy work load also predicted
      avoidance score at the time of the incident. Results are discussed in terms of
      control models of anxiety and as foci for debriefing with affected personnel.

PMID- 7820350
TI  - Emergency work experience and reactions to traumatic incidents.
AB  - The present study examined the association between volunteer emergency work
      experience, personality, and reactions to a past traumatic incident. Participants
      from randomly selected State Emergency Services and Volunteer Bushfire Brigade
      Units in New South Wales (Australia) completed four questionnaires. The data did
      not support the idea that emergency workers are hardier than most, or have
      particular coping styles. Length of volunteer emergency service was associated
      with both severity and length of reaction to a past traumatic incident. The
      number of emergency callouts and current general symptom severity were associated
      with severity of reaction to a past incident.

PMID- 7820351
TI  - The impact of disaster support work.
AB  - Limited available evidence suggests that disaster support work may have negative
      effects. This study attempts to examine the impact of disaster-related stress on
      helpers offering psychological support to victims of two major disasters, and to
      identify potential moderating factors. Sixty-seven social workers were surveyed,
      measures being taken of psychological symptomatology and wellbeing, personality
      variables, social support, life events, and various aspects of disaster support
      work. Comparison with normative data suggested that subjects were experiencing
      significant levels of stress. Two major sources of disaster-related stress were
      identified: role-related difficulties and contact with clients' distress.
      Approximately one third of the variance in helper response could be explained by
      variables reflecting coping style, prior life events and the aforementioned
      aspects of disaster support work. Follow-up data at 12 months demonstrated
      persisting high levels of stress.

PMID- 7820352
TI  - Psychological, psychosocial, and psychophysiological sequelae in a community
      affected by a railroad chemical disaster.
AB  - Psychological, psychosocial, and psychophysiological sequelae were studied in a
      community which had experienced a railroad chemical spill of 19,000 gallons of
      the toxic pesticide metam sodium. Two hundred twenty exposed residents were
      compared to 114 controls and paired on age, education, gender, race, and number
      of children. A clinical interview and physiological measurements (blood pressure,
      pulse, and cortisol level) were taken, the MMPI-2, IES Scale, Mood Scale,
      Environmental Worry, Perceived Social Support, and Perceived Control Scale and a
      questionnaire were administered. Results indicated greater levels of depression,
      anxiety, and somatic symptoms in the spill residents in addition to greater
      environmental worry and lower perceived social support. Spill residents had
      higher blood pressure and less fluctuation of cortisol levels than controls. No
      difference on litigation status was obtained except on the IES, Intrusion and the
      POMS scales. Chemical disasters are associated with a wide variety of
      psychological, psychosocial, and physiological distress.

PMID- 7820353
TI  - The role of the experimenter in field studies of distressed populations.
AB  - In laboratory research, the experimenter's role is to behave in a standardized
      manner, often following a script, in order to collect data without influencing
      the responses of subjects. However, in field studies of vulnerable or victimized
      populations, experimenters confront tasks and dilemmas at odds with this concept
      of their role. Subjects may cry; experimenters may experience strong feelings
      when witnessing adversity; normative experimental behavior may feel
      inappropriate. This paper reports on issues identified in a graduate seminar for
      nonclinically trained health psychology researchers, and describes the program of
      training provided. Paradoxically, adhering to a more detached, noninfluential
      style of interaction requires adapting a flexible, rather than a rote, behavioral
      style. Relevant skills include explicating values, developing relational and
      communications skills, and training in post-traumatic stress syndromes. By thus
      redefining the experimenter's role, ethical and practical considerations
      introduced in field studies of distressed populations can be balanced with
      laboratory values.

PMID- 7820354
TI  - Race-related PTSD: the Asian American Vietnam veteran.
AB  - This article presents a conceptual framework by which to understand race-related
      post-traumatic stress disorder (PTSD) for the Asian American Vietnam veteran. The
      framework draws from cognitive schema theory, social behaviorism, the notion of
      cumulative racism as trauma, and the assumption that bifurcation and negation of
      one's bicultural identity is injurious. Classifications of race-related stress or
      trauma that may be experienced by Asian American Vietnam veterans, with
      exemplifying clinical case material, are presented. These types of stressors
      include being mistaken for Vietnamese, verbal and physical assaults that are race
      related, death and near-death experiences that are race-related, racial
      stigmatization, dissociation from one's Asian identity, and marginalization. As
      studies of combat trauma and sexual assault forced the psychological stresses
      attendant to war and sexist oppression into public consciousness, so this article
      addresses psychological stress and trauma attendant to racism.

PMID- 7820355
TI  - Stress reactions of school-age children to the bombardment by Scud missiles: a 1
      year follow-up.
AB  - Follow-up long-term stress effects to bombardment by scud missiles were restudied
      1 year following the Persian Gulf war in a group of 326 6th, 8th, and 11th grade
      children from areas hit and not hit by the missiles. Postwar stress reactions
      were assessed by a continuous global symptom score (Frederick and Pynoos, 1988)
      and by a dichotomous PTSD index. Overall, a large drop in stress reactions was
      obtained with lapse of time. Residual long-term stress reactions were found to be
      associated with higher immediate (4-week) stress reactions, a greater degree of
      exposure, and younger age. Results were discussed in relation to residual and
      evaporation of stress reaction effect as well as in terms of childhood
      resilience.

PMID- 7820356
TI  - Post-traumatic stress disorder: evaluation of a behavioral treatment program.
AB  - The relative values of imaginal and real-life exposure exercises were tested in
      this study by randomizing 14 patients who met DSM-III-R criteria for PTSD at
      least 6 months after the initiating trauma to one of two groups. Group 1 (n = 7)
      had four, weekly, hour-long sessions of imaginal exposure followed by four,
      weekly, hour-long sessions of live exposure. Group 2 (n = 7) had the reverse
      order of four live exposure sessions followed by four imaginal exposure sessions.
      both groups improved significantly on both PTSD-specific measures and measures of
      general health post-treatment, and significantly further on 7 out of 12 measures
      at follow up 12 months post-treatment. Clinical improvement was in the older of
      65-80% reduction in target symptoms. On one measure only (problem 2--phobic
      avoidance), live exposure yielded more improvement than imaginal exposure whether
      given first or second. The importance of both live and imaginal exposure to all
      relevant cues, behavioral and cognitive, is discussed, together with the value of
      self-exposure homework for patients with PTSD.

PMID- 7820357
TI  - The historical evolution of PTSD diagnostic criteria: from Freud to DSM-IV.
AB  - The present study examined the evolution of the diagnostic criteria from the
      early writings of Sigmund Freud to the current DSM-IV. Freud's original model of
      neurosis, known as Seduction Theory, was a post-traumatic paradigm which placed
      emphasis on external stressor events. In 1897, due to a confluence of factors, he
      shifted his paradigm to stress intrapsychic fantasy as the focus of analytic
      treatment for traumatic neurosis. Freud's thinking influenced both the DSM-I and
      II classification of stress response syndromes as transient reactive processes.
      However, it is evident from his lectures in 1917-1918 that he understood the
      interrelatedness of what today is the four diagnostic categories in the DSM-IV.

PMID- 7820358
TI  - Depressive features in Holocaust survivors with post-traumatic stress disorder.
AB  - The present study was designed to explore several aspects of depressive
      phenomenology, including current symptoms, dependency (anaclitic) and self
      criticism (introjective) themes, and issues of self-efficacy, in Holocaust
      survivors with and without posttraumatic stress disorder (PTSD). The Depressive
      Subscale of the Symptom Checklist-90 (SCL-90) and the Depressive Experiences
      Questionnaire (DEQ) were administered to 23 Holocaust survivors and 18
      demographically-matched controls. Holocaust survivors with PTSD scored
      significantly higher on the SCL-90 depression scale, and portrayed more self
      criticism on the DEQ, than Holocaust survivors without PTSD and demographically
      matched non-exposed subjects. The data suggest that depressive symptoms in
      individuals who have been severely traumatized are more severe when associated
      with a concurrent PTSD. Furthermore, groups suffering different types of trauma
      may show similarities in psychological dimensions of depression.

PMID- 7820359
TI  - Post-traumatic stress disorder as a sequela of Guillain-Barre syndrome.
AB  - Post-traumatic stress disorder (PTSD) was observed in a 24 year-old female
      following severe Guillain-Barre syndrome (GBS). A review of the literature
      uncovered no previously mentioned examples of PTSD resulting from GBS or other
      medical illnesses. GBS-induced PTSD shared the features of PTSD seen following
      other traumatic events.

PMID- 7820360
TI  - The reported prevalence of physical and sexual abuse among a sample of children
      and adolescents at a public psychiatric hospital.
AB  - In this retrospective analysis of inpatient charts, a total of 298 children and
      adolescents admitted to a public psychiatric hospital over a 1-year period were
      examined for the prevalence of reported histories of physical or sexual abuse.
      Physical abuse was reported in 15% of the cases, while sexual abuse occurred in
      13%. A variety of comparisons were made examining possible differences in gender,
      age, race, diagnosis, and personality trait disturbance among the abused and
      nonabused patients. Relative to known prevalence rates as reported to child
      protective agencies, physical or sexual abuse occurred much more frequently among
      our sample of patients, suggesting the need for careful assessment of such
      histories upon admission and during treatment.

PMID- 7820361
TI  - Group treatment of adult male inpatients abused as children.
AB  - Recent research indicates that childhood abuse experiences characterize a large
      subset of psychiatric inpatients. This paper presents a time-limited pilot group
      developed for adult male abuse survivors in an inpatient setting using: (1)
      techniques adapted from the existing literature on treatment of abuse survivors;
      and (2) approaches deriving from the interface of theory and current
      manifestations of distress. The eclectic therapeutic approach incorporated
      psychoeducational, cognitive, behavioral, and art therapy techniques presented
      below in a session-by-session format.

PMID- 7820363
TI  - Immunocytochemical localization of 5 alpha-reductase in rat brain.
AB  - The presence of steroid 5 alpha-reductase in brain tissue is well-documented. In
      order to determine with precision the brain areas and nerve cell types containing
      this enzyme in adult rat, we have studied its immunocytochemical localization
      using antibodies to the sequence peptide comprising amino acids 227 to 240 of the
      enzyme. At the light microscopic level, 5 alpha-reductase immunoreactive material
      appeared to be present only in glial and ependymal cells, including tanycytes.
      Immunolabeled cells were found in high concentration in the hypothalamus,
      thalamus, hippocampus, cerebral cortex, cerebral cortex, and circumventricular
      organs. Immunoelectron microscopic studies demonstrated that immunoreactive
      material was diffusely distributed throughout the cytoplasm of glial and
      ependymal cells, thus confirming the association of 5 alpha-reductase
      immunoreactivity with nonneuronal cells. These data suggest that glial cells play
      an important role in the conversion of testosterone to dihydrotestosterone or
      progesterone to dihydroprogesterone under in vivo conditions in adult rat.

PMID- 7820362
TI  - Glucocorticoid receptor mRNA ontogeny in the fetal and postnatal rat forebrain.
AB  - Glucocorticoid receptor (GR) ontogeny and distribution in postnatal rat brain
      have been demonstrated, but onset and distribution of GR gene expression during
      fetal life has not been reported. This study focuses on the distribution of GR
      mRNA in the fetal and postnatal rat forebrain, with emphasis on hypothalamic and
      limbic structures. Time pregnant rats were decapitated at 8:30-9:30 AM on
      Gestational Days 14 (F14), F16, F17, F18, and F19. Postnatally, rats were
      sacrificed on Days 1, 4, 6, 10, and 16. Cryostat sections were subjected to in
      situ hybridization, using a cRNA probe directed to the GR-mRNA. GR-mRNA was
      detectible in the hippocamposeptal formation as early as F14. By F16, GR gene
      expression was evident in the hypothalamic paraventricular nucleus (PVN) as well.
      During late gestation (F17-F19), GR-mRNA was localized also in the thalamus,
      hippocampus, amygdala, and discrete cortical regions. Postnatally, GR-mRNA
      abundance was high in the PVN, CA1/CA2 hippocampal field, piriform cortex and
      dorsal endopiriform nucleus, specific amygdaloid nuclei, and the suprachiasmatic
      nucleus. In PVN, GR-mRNA was present prior to the onset of CRH gene expression
      (F17), which may suggest a role for GR in neuronal differentiation.

PMID- 7820364
TI  - The role of the hippocampal mineralocorticoid and glucocorticoid receptors in the
      hypothalamo-pituitary-adrenal axis of the aged Fisher rat.
AB  - The aging process has been frequently associated with hippocampal
      neurodegeneration, loss of corticosteroid receptors, and, at the same time,
      dysfunction of the hypothalamo-pituitary-adrenal (HPA) axis. We were interested
      in characterizing simultaneously the activity of the HPA axis and status of both
      corticosteroid receptors (mineralocorticoid or MR and glucocorticoid or GR) in
      the hippocampus of aged male Fisher-344 rats. We compared intact,
      adrenalectomized (ADX), and corticosterone-replaced ADX young (5-6 months) and
      old (26-27 months) rats, examining all the parameters in the same animals. Aged
      rats exhibited an unaltered basal rhythm and initial corticosterone response to
      restraint stress. However, the same old animals showed a delayed turn-off of the
      stress response and did so at different points of the corticosterone circadian
      cycle. The aged hippocampus showed a 40-50% lower MR and GR binding under all the
      conditions studied. This aging effect was not attributable to changes in the
      kinetics, affinity, or nuclear translocation of MR or GR. Intact aged rats
      exhibited also a 30-40% reduction of hippocampal MR and GR steady-state mRNA
      levels. Interestingly, after 36 h ADX only the aged hippocampus showed
      upregulation of MR and GR mRNA content to levels comparable to those in young
      rats. However, this increase in MR and GR mRNA content was not accompanied by a
      proportional increase in the Bmax of these receptors, suggesting age-related
      translational or post-translational alterations. Moreover, corticosterone
      replacement was able to reverse the ADX-induced increase of MR and GR Bmax in
      young and old hippocampi but it only reversed the upregulated mRNA levels of MR
      (and not GR) in the older group. The fact that corticosterone was able to
      modulate the biosynthetic rate of MR and GR strongly suggests that the decrease
      of receptors is functional and not simply due to cell death in the aged
      hippocampus. We propose that in the aged Fisher rat the loss of hippocampal
      corticosteroid receptors is previous to any change in the circadian rhythm of
      circulating corticosterone. Furthermore, the altered turn-off of the
      corticosterone stress response observed in the same animals may be related to the
      reduction of functional MR and GR but it is not due to high basal levels of
      corticosterone.

PMID- 7820365
TI  - A method for the isolation and culture of rat peripheral nerve vascular
      endothelial cells.
AB  - In studying autoimmune diseases of the human peripheral nervous system (PNS), in
      vitro studies involving the use of cultured rat Schwann cells, neurons, and
      disease-inducing immune system cells have provided basic information about
      disease pathogenesis. For example, T-cells that induce experimental allergic
      neuritis have been shown in vitro to damage Schwann cells, the target cell in
      these diseases. However, before making contact with Schwann cells, these T-cells
      must first pass through the blood-nerve barrier. Despite the importance of this
      interaction, no studies employing PNS endothelial cells in coculture with dorsal
      root ganglia cells to mimic the environment of the blood-nerve barrier have been
      reported. This paper describes a simple method for the isolation and culture of
      peripheral nerve vascular endothelial cells from adult rats that should
      facilitate in vitro studies of the blood-nerve barrier. Endothelial cells were
      identified by their expression of an endothelial cell marker, Factor VIII/von
      Willebrand factor. Their identity was further confirmed by their inability to
      express Thy 1.1, a fibroblast marker, and their in vitro morphology. Purity of
      endothelial cell cultures was ensured by a regular program of Thy 1.1 complement
      depletion of fibroblasts.

PMID- 7820366
TI  - Induction of c-Jun and suppression of CREB transcription factor proteins in
      axotomized neurons of substantia nigra and covariation with tyrosine hydroxylase.
AB  - In adult rats, the expression of transcription factor proteins c-Jun and CREB and
      their colocalization with tyrosine hydroxylase (TH) were investigated in neurons
      of the substantia nigra compacta (SNC) axotomized by stereotaxic unilateral
      transection of the medial forebrain bundle (MFB). Axotomized SNC neurons were
      identified by injection of the retrograde tracer horseradish-peroxidase-coupled
      gold (HRP-gold) into the ipsilateral striatum 5 days prior to MFB transection.
      Nuclear c-Jun immunoreactivity (IR) appeared 36 h after MFB transection in SNC
      neurons, was maximal after 5 days, and declined after 10 days. c-Jun-IR was
      visible in HRP-gold-labeled SNC neurons, demonstrating that c-Jun is in fact
      expressed in axotomized neurons. The constitutively expressed CREB (calcium/cAMP
      response element-binding protein, syn. CREB-1) was present in apparently all
      neuronal and glial cells in the brains of untreated rats including those SNC
      neurons that coexpressed TH. Three days following MFB transection, the nuclear
      CREB-IR disappeared in the axotomized SNC neurons labeled by TH-IR and was almost
      completely absent after 20 days in this neuronal population. The TH-IR rapidly
      declined 5 days after MFB transection, and 10 and 100 days post-axotomy the
      number of TH-labeled neurons was reduced by 52 and 80%, respectively. During this
      period, the majority of surviving TH positive neurons coexpressed c-Jun but were
      immunonegative for CREB. Between 3 and 60 days following MFB transection, the
      number of CREB-labeled glial cell nuclei increased in the ipsilateral substantia
      nigra by about 80%. Concomitantly, expression of GFAP, a marker protein for
      astrocytes, was also enhanced whereas nuclear c-Jun-, JunD-, and c-Fos-IR did not
      change in glial cells. These findings demonstrate that c-Jun can be expressed in
      axotomized neurons during the absence of CREB and suggest a role of c-Jun in the
      transcriptional control of the TH gene.

PMID- 7820367
TI  - Interaction between alcohol and interleukin-1 beta on ACTH secretion and the
      expression of immediate early genes in the hypothalamus.
AB  - We have observed that alcohol does not alter adrenocorticotropin (ACTH) released
      in response to the iv injection of interleukin-1 beta (IL-1 beta). In contrast,
      prior (-30 to -90 min) administration of moderate doses of alcohol (0.5-2.0 g/kg)
      significantly blunts ACTH secretion following the intracerebroventricular (icv)
      injection of the cytokine. We explored two possible mechanisms responsible for
      this phenomenon: Corticosteroid feedback and alcohol-induced inhibition of
      hypothalamic neuronal activation (measured through changes in c-fos and NGFI-B
      mRNA levels). Increasing plasma corticosterone levels by exposing rats to mild
      electroshocks or injecting them with corticosterone did not alter ACTH released
      by rats administered with IL-1 beta into the brain ventricles. Alcohol, which by
      itself did not stimulate c-fos or NGFI-B mRNA levels in the paraventricular
      nucleus of the hypothalamus, significantly blunted the ability of icv IL-1 beta
      to increase the expression of these immediate early genes. We conclude that the
      inhibitory influence exerted by prior alcohol treatment on ACTH released by icv
      administered IL-1 beta may reflect an interference with the stimulatory influence
      of the cytokine on hypothalamic neurons involved in the activation of the
      hypothalamic-pituitary-adrenal axis.

PMID- 7820368
TI  - Adrenalectomy selectively regulates GABAA receptor subunit expression in the
      hippocampus.
AB  - Hippocampal function is modulated by adrenal corticosteroids released in a
      diurnal rhythm or in response to stress. Hippocampal excitability is also
      modulated by the activity of gamma-aminobutyric acid (GABA), the major inhibitory
      neurotransmitter in the mammalian brain. One mechanism of corticosteroid action
      in the hippocampus is likely to be via regulation of the GABA system, including
      corticosteroid regulation of GABAA receptor expression. The GABAA receptor is a
      heterooligomeric complex composed of subunits derived from a number of distinct
      genes. We examined the effects of short-term adrenalectomy and low-level
      corticosterone replacement on mRNA levels for 5 GABAA receptor subunits. In situ
      hybridization studies demonstrated that mRNA levels for GABAA receptor alpha 1,
      alpha 2, beta 2, and gamma 2 subunits were altered in the hippocampus of female
      rats by adrenalectomy. Levels of alpha 1 and gamma 2 mRNA increased in CA3, alpha
      2 mRNA increased in the dentate gyrus, while beta 2 mRNA decreased in the dentate
      gyrus and CA2 relative to sham-operated animals following adrenalectomy. These
      effects were reversed by the addition of 100 micrograms/ml corticosterone to the
      drinking water. Adrenalectomy had no effect on the levels of beta 1 mRNA and no
      effect on any subunit examined in CA1 or the cingulate cortex. These data support
      the conclusion that corticosteroids can modulate hippocampal excitability through
      the site-specific regulation of the expression of specific GABAA receptor
      subunits. Corticosterone-induced changes in subunit expression might alter
      GABAergic synaptic inhibition by altering the density of GABAA receptors or
      altering the subunit composition and thereby the pharmacological properties of
      the receptors.

PMID- 7820369
TI  - Neuropeptide-Y neurons projectioning to the medial septum-diagonal band do not
      have access to fenestrated capillaries in the rat brain.
AB  - The aims of this study were to (1) determine the localization of neuropeptide-Y
      (NPY)-containing perikarya which project to the medial septum-diagonal band
      (MSDB), a brain region rich in gonadotropin-releasing hormone (GnRH) producing
      perikarya, and (2) determine if NPY neurons have access to fenestrated
      capillaries as well. Fluorescent retrograde tracing after microinjection of
      fluororuby (FR) into the MSDB, and peripheral injection of fluorogold (FG), was
      used in combination with immunofluorescence for NPY. Injection of FR into the
      MSDB resulted in retrograde labeling of neurons in the hypothalamic arcuate
      nucleus (ARC) and brainstem noradrenergic cell groups A1 and A2, as well as other
      regions. The largest populations of NPY neurons were located in the ventromedial
      ARC and several of these perikarya contained FR indicating that they project to
      the MSDB. Defined cell groups in the areas A1 and A2 of the brainstem also
      contained large numbers of NPY neuron perikarya, and several of these contained
      FR. In addition, we observed isolated incidences of FR-labeled NPY perikarya in
      the amygdala and hippocampus. A small population of NPY neurons in the ARC
      contained FG, indicating that they are in contact with fenestrated capillaries
      and hence are neuroendocrine cells; however, none of these neurons contained FR.
      We suggest that NPY neurons in the ARC modulate GnRH function via innervation of
      the MSDB and LH release via release into fenestrated capillaries of the
      hypophysial-portal system.

PMID- 7820370
TI  - The role of extracellular calcium in the neuropeptide-Y-induced increase in
      cytosolic calcium in human erythroleukemic (HEL) cells.
AB  - Cytosolic calcium changes were followed in human erythroleukemic (HEL) cells
      loaded with the fluorescent probe fura-2. Peak increases in cytosolic calcium
      were reduced by two-thirds in cells suspended in Ca(2+)-free medium, suggesting
      that calcium entry significantly contributes to the increases in cytosolic
      calcium after NPY receptor stimulation. To establish if Ca2+ entry was a direct
      consequence of receptor stimulation or indirectly via depletion of Ca2+ stores,
      the latter were totally or partially depleted by treatment with cyclopiazonic
      acid or alpha-thrombin, respectively, in Ca(2+)-free medium. Partial depletion
      markedly diminished and full depletion suppressed the NPY-induced response in
      Ca(2+)-free medium. After full depletion, the recovery of the NPY-induced
      increase in cytosolic calcium was dependent on the length of [Ca2+]e reexposure,
      suggesting a direct entry of Ca2+ to the storage sites followed by release to the
      cytosol. After partial depletion, transient reexposure to [Ca2+]e did not by
      itself increase cytosolic calcium levels or refill the stores as NPY stimulation
      did not increase cytosolic calcium if [Ca2+]e was chelated prior to stimulation.
      However, if partially depleted cells were exposed to NPY in the presence of
      readded [Ca2+]3, the peak calcium response was similar to that of control cells,
      indicating that partially depleted calcium stores can be refilled from
      extracellular sources only if NPY receptors are stimulated. Analysis of the data
      suggests that in HEL cells the entry of calcium and mobilization from
      intracellular stores are in series processes and that entry is triggered by
      intracellular levels only under extreme depletion, while under physiological
      conditions calcium entry is coupled to receptor stimulation.

PMID- 7820371
TI  - Pubertal development of estrogen receptors in the rat brain.
AB  - The regional distribution of estrogen receptors (ER) was studied in the brain of
      the female rat over the peripubertal period. Increases were observed in nuclear
      ER occupation as well as cytosolic progestin receptor induction in the period
      leading up to the time of vaginal opening, consistent with an increased
      availability of estrogen to the brain. ER binding capacity, however, was
      remarkably similar in pre- and postpubertal rats. Using a microdissection-based
      nuclear ER assay, small increases in the total ER content of the hypothalamic
      ventromedial and arcuate nuclei were observed in the female at around the time of
      the onset of reproductive cyclicity. In vivo autoradiographic studies confirmed
      the existence of a small increase in estrogen binding in these two brain regions
      at around the time of vaginal opening, as well as transient increases in estrogen
      retention within the preoptic area and bed nucleus of the stria terminalis. These
      changes in estrogen binding in the brain may play a role in pubertal alterations
      in the feedback sensitivity of the brain to circulating estrogen.

PMID- 7820372
TI  - cDNA cloning of regeneration-specific genes in rice by differential screening of
      randomly amplified cDNAs using RAPD primers.
AB  - A simple method for differential screening of randomly amplified cDNAs using
      primers for detection of randomly amplified polymorphic DNA (RAPD) has been
      developed. To detect and clone differentially expressed genes during
      regeneration, we compared mRNAs from rice calli before the induction of
      regeneration, 7 days after induction of organogenesis, and 7 days after induction
      of embryogenesis. The cDNAs were amplified by the polymerase chain reaction (PCR)
      with a single RAPD primer and were separated by agarose gel electrophoresis. A
      number of differentially amplified bands were detected. Five of the specific
      bands were cloned and their expression was analyzed by Northern hybridization. We
      isolated a cDNA clone which is specific to organogenesis, two clones which are
      specific to embryogenesis, and two clones which are common to organogenesis and
      embryogenesis but not present in unorganized calli. Two of the isolated clones
      are expressed at low levels. Thus, this method is useful for cloning of
      differentially expressed genes whose transcripts are of low abundance. Expression
      of one of the embryogenesis-specific cDNA clones, pCRE2, was analyzed in detail.
      The pCRE2 transcript accumulates transiently in calli after the induction of
      embryogenesis, and its accumulation in planta was specific to zygotic embryos.

PMID- 7820373
TI  - Chalcone synthase from Camellia sinensis: isolation of the cDNAs and the organ
      specific and sugar-responsive expression of the genes.
AB  - Three full-length cDNAs (CHS1, CHS2 and CHS3) encoding chalcone synthase (CHS; EC
      2.3.1.74) were isolated from young leaves of Camellia sinensis. Each cDNA encoded
      389 amino acid residues, which showed 93-96% identity to one another.
      Oligonucleotides were synthesized on the basis of the 5'-untranslated sequences
      of the cDNAs and their corresponding transcripts could be distinguished. The
      CHS1, CHS2 and CHS3 transcripts were abundant in the leaves and stems. After an
      initial treatment with water in darkness, the transcripts fell to very low levels
      in the young leaves. These levels were increased by a subsequent treatment with
      fructose, sucrose or maltose in darkness, and they increased still further upon a
      treatment with glucose, sucrose or maltose under continuous light. These results
      indicate that the CHS1, CHS2 and CHS3 transcripts are expressed in various organs
      and respond to sugars in young leaves in a similar manner. The effect of
      continuous light is also discussed.

PMID- 7820375
TI  - Two isolectins from leaves of winged bean, Psophocarpus tetragonolobus (L.) DC.
AB  - Two isolectins were isolated from leaves of winged bean and characterized. They
      differed from each other in terms of their immunological properties,
      hemagglutinating activities, sugar inhibition patterns, and amino acid
      compositions. Both lectins were acidic and one of them (L-I), which was inactive
      toward trypsinized human type O erythrocytes, was similar to one of green shell
      lectins (WGS-1); which resembled basic seed lectin in its immunological
      properties. The amino-terminal sequence of L-I was homologous to that of WGS-1.
      The amino acid composition of L-I was similar to that of basic seed lectin, but
      the extent of the homology between amino-terminal sequences was low when L-I and
      basic seed lectin were compared. Examination by ELISA revealed that L-I and WGS-1
      were distinct from the basic lectins of seeds and tuberous roots. L-I had a
      disulfide bridge between two subunits and it exhibited high hemagglutinating
      activity toward human type A erythrocytes, as compared to its activity toward
      other erythrocytes. By contrast, the properties of a second acidic lectin from
      winged bean leaves (L-II) were very similar to those of acidic lectins from seeds
      and tuberous roots, and the similarities extended as far as the immunological
      properties.

PMID- 7820374
TI  - A serine protease in soybean seeds that acts specifically on the native alpha
      subunit of beta-conglycinin.
AB  - A proteolytic activity directed against the alpha subunit of beta-conglycinin was
      detected in resting mature seeds of the soybean [Glycine max (L.) Merrill]
      cultivar Keburi. The relationship between pH and activity and the effect of
      protease inhibitors revealed that the enzyme was a neutral/alkaline serine
      protease. The proteolysis of the alpha subunit of beta-conglycinin yielded a
      specific product with a molecular weight of about 47,000, as determined by SDS
      PAGE, but the enzyme had no activity against the beta subunit. The amino acid
      composition, the molecular weight and the amino-terminal amino acid sequence of
      the proteolytic product revealed that the action of the enzyme on the alpha
      subunit was specific, with cleavage occurring only at the R126-R127 peptide bond
      of the alpha subunit. These characteristics of the protease indicate that the
      enzyme is a novel protease that has not previously been recognized in soybean
      seeds.

PMID- 7820376
TI  - [Health education in Burundi: peer education in practice].
AB  - Because almost half of the patients diagnosed in health centers in Burundi
      suffered from illnesses related to impure water or inadequate sanitation, the
      Hygiene Education and Training Programme was created to assure the efficient use
      of water and sanitation infrastructures by the population of Burundi. A specific
      organizational unit, linked to the ministry of Public Health was created to
      implement the programme. With the objective of changing non-hygienic behaviour
      related to water use and sanitation, hygiene education was carried out by field
      teams using interpersonal peer communication methods in people's homes during a
      series of education campaigns that each last three months. The programme was
      directed primarily to households composed of men, women and children, with
      particular attention given to women and children, who have the primary
      responsibility for household hygiene. A participatory approach was employed that
      used teams of volunteers chosen by and from the population, and who visited
      households twice during each campaign. Audiovisual materials and messages for
      each campaign were developed in collaboration with the population. The field
      teams were motivated by a regular programme of training, an intense support and
      monitoring system, and the availability of audiovisual materials for hygiene
      education, as well as a system of prizes that was added recently. After 18 months
      of experience, it is possible to say that the approach is both feasible and
      effective. The population reacted positively to the hygiene education that was
      offered and a degree of behaviour change was observed.

PMID- 7820377
TI  - [Fighting cholera in shanty-town. Successful experience of a Quebec project
      adapted to Peru].
AB  - Originally designed in Quebec, the MOI project was a collaboration between two
      professors of social work from Quebec and two members of the Peruvian NGO called
      SUR in Villa de Salvador, one of poorest slum areas on the outskirts of Lima. The
      approach is founded on the notion that the body is the primary instrument through
      which a person can interact with the world around him or her, and that the
      physical and mental health of an individual exists within the context of healthy
      conditions of life that must include at least a basic social and health
      infrastructure as well as healthy hygiene practices on the part of individuals,
      families and the local community. Preschool children (ages 4-6), study a
      different part of the body and its proper care each week through classroom
      observation games. Parents' help is requested to modify unhealthy conditions, at
      the same time to enrich the children's experience and to mobilize the community
      to improve health conditions. During the 1991 cholera epidemic, not a single case
      was counted in the experimental district, despite its clearly socio-economically
      impoverished status, and despite the fact that the Ministry of Health recorded
      86,650 cases in the Lima-Callao district, accounting for about 40% of the total
      number of cases in the Peru. The prior work made it easier to explain how cholera
      is spread and what special new measures needed to be taken in addition to the
      hygiene habits already taught.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7820378
TI  - Gay and lesbian education in Dutch schools.

PMID- 7820380
TI  - Bullying at school. Basic facts and an effective intervention programme.

PMID- 7820379
TI  - Oral rehydration therapy promotion. An education--communication experiment.

PMID- 7820381
TI  - Can we talk of health promotion at a time of so many regressions?

PMID- 7820382
TI  - Towards a sustainable Europe: Helsinki charter on environment and health.

PMID- 7820383
TI  - The role of NGOs in community health and development.

PMID- 7820384
TI  - Reactive airways dysfunction syndrome.
AB  - Reactive airways dysfunction syndrome (RADS) is an asthma-like
      bronchoconstriction state which develops after a short-term exposure to highly
      irritating volatile substances. Although some of the clinical manifestations can
      be considered as very similar to those of asthma (e. g. inflammation,
      hyperresponsiveness and reversibility of the bronchial constriction) the most
      essential difference lies in the absence of asthma attacks after exposure to
      small amounts of causative agents few weeks after onset. Thus, the mechanism of
      RADS cannot be considered to be of an allergic origin. This is supported by the
      results of the pathomorphologic biopsies taken from bronchi which usually show
      neutrophilic and lymphocytic infiltrations as well as frequent and severe
      destruction of the bronchial epithelium. Eosinophilic infiltrations and basement
      membrane thickness have never been found. The therapy of severe dyspnoea attacks
      is similar to that of bronchial asthma. Factors that cause RADS comprise a wide
      range of volatile irritant substances, provided that they occur in high
      concentrations. Exposure to isocyanates in plumbers heating polyurethane pipes
      seems to be the major cause of RADS in Poland.

PMID- 7820385
TI  - Assessment of the respiratory system in workers occupationally exposed to
      phosphorite and apatite dusts.
AB  - The respiratory system in 118 male workers occupationally exposed to phosphorite
      and apatite dusts was assessed. Subjective, physical and spirographic
      examinations were performed and chest X-ray pictures were taken. No significant
      differences between the exposed workers and the control group were found. There
      was only a statistically significant decrease in spirometric parameters in the
      exposed group in comparison with controls. There was no such relationship in
      regard to the length of employment and smoking habit. In the exposed group there
      were no significant disturbances of the lung ventilation efficiency.

PMID- 7820386
TI  - Endotoxin in the occupational environment of bakers: method of detection.
AB  - The present study was conducted in a large mechanical city bakery. The AS-50
      aspirators equipped with cellulose membrane filters were used for dust sampling.
      Airborne microbial content was assessed by means of sedimentation and aspiration
      using an Andersen sampler on Petri plates containing McConkey's medium. The
      following Gram-negative rods were detected in the bakery atmosphere: Erwinia
      herbicola, Acinetobacter Lwoffi and Klebsiella oxytoca, in concentrations ranging
      from 1.4 10(4) to 3.5 10(5) colony forming units per cubic meter (cfu/m3).
      Endotoxin concentration in flour dust sampled in selected work areas of the
      bakery ranged from 6.7 micrograms of endotoxin per gram of dust (micrograms/g) to
      20.3 micrograms/g. Endotoxin level in the air was 0.04-0.05 micrograms of
      endotoxin per cubic meter (micrograms/m3). The results of our show that
      aspiration sampling is necessary for evaluation of airborne bacterial content and
      demonstrate the efficacy of the Limulus test of varying sensitivity to assay
      endotoxin level in the airborne dust. The advantage of this method is the
      possibility of assessing endotoxin in crude dust extracts.

PMID- 7820387
TI  - Spatial distribution of negative health indices in ecological hazard areas in
      Poland.
AB  - Spatial distribution of negative health indices (relative risk, synthetic
      measure) was demonstrated in 27 ecological hazard areas (EHAs) in Poland. For
      comparison reference areas were selected. The health indices were used for
      developing a general index of harmfulness characteristic for individual EHA. The
      health status ranking in EHAs is useful in setting priorities for remediation.

PMID- 7820388
TI  - Study of volatile noxious compounds composition during the use of lubricant
      coolant fluids.
AB  - The aim of the study was the gas chromatography (GC) separation and mass
      spectrometric (MS) identification of volatile compounds mixture generating in the
      air of work environment when lubricant-coolant fluids (LCFs) are used. GC/MS
      method was used for determining mixture ingredients. Hydrocarbons, carbonil
      compounds, esters, oxiranes and aromatic amines were identified in test samples.
      When LCFs are used, monitoring of highly toxic substances (aromatic amines,
      carbonil compounds and oxiranes) makes the assessment of risk and exposure more
      complete.

PMID- 7820389
TI  - Sensory irritating properties of cyanuric chloride as revealed with
      plethysmographic method.
AB  - Sensory respiratory irritation properties of cyanuric chloride (2,4,6
      trichlorotriazine; CC) were studied in mice. For this purpose, the respiratory
      rate was measured in Balb/C male mice by means of the whole body plethysmographic
      method. Each animal was placed in a body plethysmograph attached to a small (0.25
      m3) dynamic inhalation chamber and exposed to various concentrations (2.1, 6.7,
      9.1, 11.7 and 14.6 mg/m3) of CC. Respiratory rates were recorded before, during
      and after termination of the exposure. It was found that exposure to CC caused a
      concentration-dependant decrease of respiratory rates in mice. After termination
      of exposure fast and full recovery of respiratory rates were observed within 5
      minutes. RD50 value calculated with probit method was established as 5.9 (1.3
      13.9 for 95% confidence limits) mg/m3. The slope of the dose response curve was
      1.366 (0.78). It is concluded that cyanuric chloride is a strong respiratory
      irritant.

PMID- 7820390
TI  - Toxic effects of subchronic combined exposure to n-butyl alcohol and m-xylene in
      rats.
AB  - Effects of combined exposure to m-xylene and n-butyl alcohol in the conditions of
      subchronic inhalation experiment in rats were examined. Rats were exposed to
      vapours of individual solvents at concentrations of 50 and 100 ppm and their 1:1
      mixture at concentrations of 50 + 50 ppm and 100 + 100 ppm, 6 h/day, 5 days/week
      for 3 months. No significant changes in body weight gain, in absolute and
      relative organ weights and clinical biochemistry parameters were observed. The
      motor coordination disturbances caused by mixture of m-xylene and n-butyl alcohol
      at concentrations of 100 + 100 ppm were identical as those caused by n-butyl
      alcohol at concentration of 100 ppm. Thus, in condition of combined exposure, the
      toxic effect of m-xylene was not added to the effect of n-butyl alcohol.
      Significant increase in sensitivity to pain in animals exposed to m-xylene at
      both concentrations, and parallel lack of changes in the pain sensitivity in
      animals exposed to n-butyl alcohol and to the solvent mixtures was observed. n
      Butyl alcohol provoked the increase of lipid peroxidation in hepatic microsomes
      without any induction of cytochrome P-450 monooxygenases, m-Xylene did not affect
      the activity of monooxygenase and lipid peroxidation rate in hepatic microsomes
      and moreover, in the case of combined exposure it abolished the effect on n-butyl
      alcohol. Results obtained in condition of acute and subchronic inhalation
      exposure interpreted jointly, indicate the less than additive toxic effect of
      combined exposure to m-xylene and n-butyl alcohol.

PMID- 7820391
TI  - Evaluation of occupational exposure to noise from the hearing conservation point
      of view.
AB  - The paper presents the classification of noise according to its parameters (among
      others to the frequency range) to be considered as responsible for the potential
      hearing damage. Polish and international standards for various types of noise
      assessment at work places (including impulse noise) are discussed. Basic
      instruments for noise measurements are described. Finally, attention is paid to
      various methods used for the reduction of exposure to noise and to protect the
      hearing of workers.

PMID- 7820392
TI  - Is ethics universal?

PMID- 7820393
TI  - Review article: radiation protection in dental radiology.
AB  - Dental radiology represents the most frequent diagnostic radiological
      investigation in the industrialized world, with over 16 million examinations
      performed annually in England and Wales alone. Although individual doses and
      risks are low in dental radiography, the collective dose is not inconsiderable
      and many examinations are performed in younger age groups. Radiation protection
      of patients in dental radiology is achieved in three ways: by appropriate
      selection criteria for patients and equipment, methods of dose limitation and
      quality assurance procedures. There is a lack of agreed radiographic selection
      criteria to guide British dentists and this may lead to overuse of certain
      techniques, principally panoramic radiography. In intraoral radiography the use
      of fast (E-speed) film and rectangular collimation offer dose reductions of
      approximately 50% and 60%, respectively. Constant potential X-ray units and rare
      earth filtration permit further reductions. In panoramic and cephalometric
      radiography, improved collimation offers a simple means of dose limitation, while
      doses can be reduced by up to one-eighth by combining the use of constant
      potential X-ray units, rare-earth intensifying screens and rare-earth filtration.
      Lead protection of the abdomen has little relevance to radiation protection;
      however, thyroid shielding has some value. Concern has been expressed about the
      poor diagnostic quality of radiographs taken in the general dental services.
      Consequently a quality assurance programme plays an essential part in dental
      radiation protection by improving diagnostic yield and limiting repeat
      examinations.

PMID- 7820394
TI  - Low-reflectivity periportal collar on hepatic ultrasound.
AB  - A low attenuation periportal collar is frequently found on computed tomography
      (CT) in association with a variety of liver diseases and other conditions
      (Lawson, T L, Thorsen, M K, Erikson, S J et al, Periportal halo: a CT sign of
      liver disease, Abdom. Imaging, 18, 42-46 (1993)). Abnormal periportal intensity
      has been reported on magnetic resonance imaging (MRI) in various hepatobiliary
      diseases. Transient low reflectivity periportal cuffing has recently been
      described and was presumed to be due to periportal lymphoedema associated with
      malignant lymphadenopathy. We report the finding of such bands in four patients
      with chronic hepatobiliary disease and present the associated histological
      findings.

PMID- 7820395
TI  - Is there still a role for lymphography in the management of early stage carcinoma
      of the cervix?
AB  - The value of lymphography in the management of carcinoma of the cervix is
      controversial and in many institutions has ceased to be used as part of routine
      staging. We present the results of 103 patients with carcinoma of the cervix
      treated by radical radiotherapy alone at the Royal Marsden Hospital between 1984
      and 1990 all of whom had a staging lymphogram and computed tomography (CT) of the
      abdomen and pelvis as part of their routine staging prior to therapy. Our results
      show that 72 patients (70%) had no involved nodes detected on either CT or
      lymphography (LG--ve/CT--ve) while 16 patients (15.5%) were thought to have
      involved lymph nodes on lymphography alone but not on CT (LG+ve/CT-ve). The
      remaining 15 cases (14.5%) had involved lymph nodes on both CT and lymphography
      (LG+ve/CT+ve). There were no patients shown to have involved lymph nodes on CT
      with a negative lymphogram. Survival analysis on these three groups showed that
      patients in the LG+ve/CT+ve group did worse than the other two groups with only a
      28% 5 year survival compared with 60% (LG-ve/CT-ve group) and 64% (LG+ve/CT-ve
      group) (p < 0.1). This effect of lymph node involvement disappeared in a
      multivariate analysis using Cox regression when stage came out as the strongest
      factor affecting survival. After controlling for stage, a further analysis of
      patients with only stage I and II disease has shown that patients who were
      LG+ve/CT+ve still did significantly (p < 0.05) worse (30% 5 year survival) than
      the other two groups: LG-ve/CT-ve group altered clinical management in 5/6
      patients with stage I or IIA disease who avoided radical surgery and who were
      given a parametrial boost to the site of lymph node involvement. The possible
      benefit of this additional treatment to explain the higher survival rate of
      patients in the LG+ve/CT-ve group is discussed further. We conclude that
      lymphography still has a limited role to play in patients with early stage
      disease (I or IIA) who do not appear to have involved lymph nodes on CT scanning.

PMID- 7820396
TI  - Recurrent upper tract urothelial tumours: the use of loopography following
      cystectomy for bladder cancer.
AB  - Recurrent upper tract tumours following cystectomy for transitional cell
      carcinoma are not uncommon. Conventional follow-up to identify preclinical
      recurrent disease often involves a combination of excretory urography and urine
      cytology. This study investigates the possible advantages of loopography in the
      follow-up of these patients. 41 patients who had undergone cystectomy and ileal
      loop diversion for transitional cell carcinoma of the bladder were studied. At
      the time of evaluation with a loopogram, eight out of 41 (19.5%) were
      symptomatic. Loopography was well tolerated by all of the patients with no
      reported side-effects or complications from the procedure. Six out of 41 (14.6%)
      of the loopograms demonstrated an abnormality with recurrent transitional cell
      carcinoma identified in two patients. In only one case was excretory urography
      necessary where a ureteric stricture prevented retrograde imaging of the upper
      tract. Loopography is a safe and well-tolerated investigation for the follow-up
      of these patients. Excretory urography should be reserved for cases where upper
      tract imaging is impaired because of obstruction within the loop or ureters.

PMID- 7820397
TI  - Hepatic ultrasound findings in the glycogen storage diseases.
AB  - Hepatic ultrasonography was performed on 70 patients with the hepatic glycogen
      storage diseases (GSDs) to assess parenchymal echogenicity. 27 patients had GSD
      I, 24 had GSD-III and 19 had GSDs-VI/IX; ages varied from 0.6 to 35.7 years
      (median 11.7). 31 (44%) had normal or mild parenchymal changes, and 41% (11/27)
      of those with GSD-I, 25% (6/24) with GSD-III and 11% (2/19) with GSDs-VI/IX had
      marked changes. No relationships were found between the ultrasonographic
      appearances and other indices of metabolic control, including plasma
      triglycerides, total cholesterol or height standard deviation score. Seven adult
      patients (21-29 years) were found to have hepatic tumours: six with GSD-I and one
      with GSD-III. Those with GSD-I and tumours tended to have the more severe hepatic
      parenchymal changes. We conclude that ultrasonography may be useful in
      identifying patients with GSD-I at risk of hepatic tumour formation.

PMID- 7820398
TI  - Estimation of fetal volume by magnetic resonance imaging and stereology.
AB  - The current methods to monitor fetal growth in utero are based on ultrasound
      image measurements which, lacking a proper sampling methodology, may be biased to
      unknown degrees. The Cavalieri method of stereology guarantees the accurate
      estimation of the volume of an arbitrary object from a few systematic sections.
      Non-invasive scanning methods, and magnetic resonance imaging (MRI) in
      particular, are valuable tools to provide the necessary sections, and therefore
      offer interesting possibilities for unbiased quantification. This paper describes
      how to estimate fetal volume in utero with a coefficient of error of less than 5%
      in less than 5 min, from three or four properly sampled MRI scans. MRI was chosen
      because it does not use ionizing radiations on the one hand, and it offers a good
      image quality on the other. The impact of potential sources of bias such as fetal
      motion, chemical shift and partial voluming artefacts is discussed. The methods
      are illustrated on four subjects monitored between weeks 28 and 40 of gestation.

PMID- 7820399
TI  - Single breath-holding three-dimensional magnetic resonance portography with bolus
      injection of Gd-DTPA in subjects with normal liver: a comparison with two
      dimensional time-of-flight technique.
AB  - Two-dimensional time-of-flight (2D-TOF) magnetic resonance (MR) portography tends
      to produce general image degradation owing to the phase discrepancy caused by
      multiple breath-holding. To solve this problem, three-dimensional (3D)-MR
      portographies were reconstructed from image data acquired with a bolus injection
      of Gd-DTPA with single breath-holding in 20 subjects with normal liver function.
      2D-TOF MR portographies were obtained beforehand for the comparison. All the
      images were displayed in a cine mode for the two MR angiographic techniques.
      Visualization was assessed as positive when the vessel was visualized without
      disruption. 3D-MR portography produced a positive rate of over 80% for all but
      the left first-order branch. With the 2D-TOF techniques, however, only the portal
      trunk and left second-order branches were visualized at this rate. The positive
      rate for most portal branches was significantly higher with 3D-MR portography
      than with the 2D-TOF technique. In conclusion, 3D-MR portography makes it
      possible to depict the portal venous system without disruption using a short
      measurement time with single breath-holding and has the potential to become a
      powerful method for abdominal MR angiography.

PMID- 7820401
TI  - Cine magnetic resonance imaging of pulsatile cerebrospinal fluid flow using
      CSPAMM.
AB  - Spatial modulation of magnetization (SPAMM) is a well established imaging
      technique which superimposes a tagging pattern on conventional magnetic resonance
      (MR) images, allowing movement to be visualized. A modification to the SPAMM
      technique, called complementary spatial modulation of magnetization (CSPAMM),
      which improves the contrast of the tagging pattern is explained. The application
      of CSPAMM to the visualization of pulsatile cerebrospinal fluid flow (CSF) using
      an 8 frame cardiac-gated cine sequence is described. Various combinations of
      binomial pulses, up to the fifth order, were investigated to see which produces
      the optimum tagging pattern in the CSPAMM images. The flip angles of the imaging
      RF pulses were studied to see which would give equal maximum CSF signal intensity
      in all the cine images. The optimized cine CSPAMM technique was compared in vivo
      with SPAMM and CSF motion was found to be more easily visualized in the CSPAMM
      images.

PMID- 7820400
TI  - Non-invasive assessment of diffuse liver disease by in vivo measurement of proton
      nuclear magnetic resonance relaxation times at 0.08 T.
AB  - 44 patients with a range of parenchymal liver diseases diagnosed by biopsy or
      laboratory investigations underwent proton nuclear magnetic resonance (NMR)
      relaxometry of the liver at 0.08 T. T1 maps were produced using an interleaved
      saturation recovery and inversion recovery sequence and T2 maps using a four echo
      Carr-Purcell-Meiboom-Gill sequence. Significantly raised relaxation times
      compared with a previously studied group of 42 normal volunteers were found in
      groups of patients with alcoholic cirrhosis (p < 0.001 for T1 and T2), chronic
      active hepatitis (CAH) (p < 0.01 for T1 and T2) and minor liver abnormalities (p
      < 0.01, T2 only). T1 was significantly higher in cirrhotics than in patients with
      CAH (p < 0.002) and minor abnormalities (p < 0.001). This suggests a role for
      relaxometry in the confirmation of the presence of cirrhosis (sensitivity = 75%,
      specificity approximately 97%, taking T1 > 266 ms as a positivity criterion).
      Reduced T2 values were found in patients with liver iron overload prior to
      venesection (p < 0.001 versus normals, p < 0.02 versus venesected patients).
      Although this latter test has relatively low sensitivity and specificity, it may
      have a role in the monitoring of treatment for iron overload.

PMID- 7820402
TI  - Ultrasound quantitation of respiratory organ motion in the upper abdomen.
AB  - Organ motion can cause artefacts in abdominal imaging particularly with magnetic
      resonance imaging (MRI), and may often limit the diagnostic quality of an image.
      If spatial resolution and image quality are to improve in MRI and other imaging
      techniques, a more detailed understanding of organ motion is required. Despite
      the importance of organ motion little quantitative information is available to
      date. This study was the continuation of work instigated to investigate and
      quantify respiratory movements of upper abdominal organs for a group of healthy
      volunteers in order to provide the design criteria for a motion test object for
      use in MRI. A previous phase of the project allowed construction of a test object
      but refinements were needed to represent respiratory motion more closely as a
      consequence of the data presented in this paper. Improvements in the scanning
      technique and the recording procedure have revealed that, contrary to our initial
      findings, motion of the diaphragm and liver is predominantly in the superior
      inferior (SI) direction with an average displacement (+/- SD) (quiet respiration)
      of 12 +/- 7 mm (range 7-28 mm) and 10 +/- 8 mm (range 5-17 mm), respectively. For
      some volunteers, motion of the kidneys can be complex, especially during deep
      inspiration. New data have been provided by this phase of the motion study on the
      displacement, velocity and acceleration of abdominal organs as a function of
      time. These data show that MRI motion artefact reduction techniques which assume
      that either organ displacement, velocity or acceleration are constant are only
      applicable during certain phases of the respiratory cycle.

PMID- 7820403
TI  - Reduction of radiation doses in leg lengthening procedures by means of audit and
      computed tomography scanogram techniques.
AB  - Children with congenital bone dysplasias may benefit from leg lengthening
      procedures. Such procedures, by necessity, require frequent and regular imaging.
      It is necessary to minimize the total radiation dose to these patients, and
      particularly the dose to the gonads. In the present study the films of 13
      patients who had completed leg lengthening procedures were reviewed. The number
      of films was assessed together with the use of appropriate gonad shielding. In a
      second part of the study, thermoluminescent dosemeter measurements of radiation
      doses to a phantom were made for both plain radiographs (with and without gonad
      protection) and computed tomography (CT) scanograms. The results show that audit
      plays an important role in assessing radiographic practice with respect to
      accurate placement of gonad protection and confirm that a significant dose
      reduction can be accomplished by careful use of this lead shielding. Dose
      reduction can also be achieved by using alternative radiographic techniques such
      as CT scanograms. Other techniques such as ultrasound or dual-energy X-ray
      absorptiometry are briefly discussed. These may play an important additional part
      in the reduction of total radiation dose to the patients.

PMID- 7820404
TI  - Local control versus dose or overall time: from coefficients to percentages.
AB  - When clinical results are analysed to find the treatment variables which affect
      the outcome, two types of multivariate analysis are done. Firstly, a
      determination of which variables are important is made: from age, gender, stage,
      histology, total dose, overall time, etc. Secondly, a quasi-biological model may
      be set up which includes those variables, e.g. Function (p) = Variable 1 +
      Variable 2 + ... + alpha x dose + beta x dose x (dose per fraction) - gamma x
      (overall time) where p is the probability of local control and "Function" is a
      logit or double-log function. The coefficients thus determined are often
      presented simply in raw form, or as ratios such as alpha/beta or gamma/alpha
      where any conversion factors from "Function (p)" to percentages are assumed
      conveniently to cancel out. However, it is mathematically possible to convert
      each coefficient directly into "percent change in local control per unit dose"
      (for alpha), or "percent per unit time" (for gamma), without recourse to the
      obvious convenience of the ratios. These converted values are more understandable
      than the coefficients themselves. They mean the rate of change of local control
      with (for example) total dose if overall time and dose per fraction were held
      constant; or rate of loss of local control with prolongation if total dose and
      dose per fraction were held constant. Even though heterogeneity may alter these
      slopes considerably from the theoretically maximum Poisson slopes, they still
      tell us what is happening averaged over the group of patients being studied, with
      often interesting insights.

PMID- 7820405
TI  - High dose rate versus low dose rate brachytherapy for squamous cell carcinoma of
      the cervix: an economic analysis.
AB  - Brachytherapy is an established and important part of the management of invasive
      carcinoma of the cervix. Available evidence suggests that low dose rate (LDR) and
      high dose rate (HDR) are equivalent in terms of tumour control, adverse effects
      and survival. Proponents of outpatient HDR argue that it is less costly than LDR,
      but no economic evaluation has been published. We compared the costs of HDR and
      LDR (capital, operating, maintenance, source and operating costs) for Nucletron
      intracavitary equipment under alternative assumptions about the number of
      patients treated per year, the number of insertions per patient and discount
      rate. For example, for 3 HDR fractionations compared with 1 LDR fractionation,
      the LDR-3 (Nucletron) is the most cost-effective, practical machine for up to 40
      patients per year. Although LDR-3 is more cost effective for a greater number of
      patients, HDR would be recommended for more than 40 patients a year for practical
      reasons. Similarly, for 5 HDR compared with 2 LDR fractionations, LDR-3 would be
      recommended for up to 20 patients per year and HDR for a greater number of
      patients. Recommendations for other HDR/LDR fractionations and annual number of
      patients seen can be derived from the model. This recommendation is based on no
      cost sharing with other sites. Cost sharing was beyond the scope of this
      analysis, though the principles are similar to the ones used. The model may be
      adapted to help equipment decision-making for a brachytherapy programme for an
      individual centre.

PMID- 7820406
TI  - Absorbed dose distribution measurements in brachytherapy using ferrous sulphate
      gel and magnetic resonance imaging.
AB  - Measurements of spatial dose distribution by means of Fricke gel dosimetry and
      magnetic resonance imaging (MRI) are reported for two different brachytherapy
      applications: a configuration of three parallel linear high dose-rate (HDR)
      microSelectron 192Ir source trains and a low dose-rate (LDR) 106Ru eye
      applicator. The presented results verify that sufficient radiation induced change
      in spin-lattice relaxation time (T1) is obtained within the gel dosimeter to
      achieve satisfactory resolution for both the HDR 192Ir source train and the LDR
      106Ru applicator. Satisfactory spatial resolution is also obtained, so that the
      large dose gradients of the brachytherapy sources can be visualized by MRI of
      irradiated dosimetry gels. A reliable representation of the relative dose level
      is achieved by calculated T1 images. The presented study supports the use of dose
      distribution measurements by means of gel dosimetry and MRI in complex
      brachytherapy applications.

PMID- 7820407
TI  - Radioiodine ablation of residual tissue in thyroid cancer: relationship between
      administered activity, neck uptake and outcome.
AB  - A retrospective review was performed to evaluate the effectiveness of radioiodine
      in the ablation of residual thyroid tissue after surgery for differentiated
      thyroid cancer. 121 patients were treated at the Princess Margaret Hospital,
      Toronto, Canada between 1977 and 1989, with the activity of radioiodine
      determined empirically. Ablation of residual thyroid was determined by 131I
      nuclear scans, using absent visible uptake (compared with background) as the
      criterion for successful ablation. 97 patients (80%) had successful ablation of
      residual thyroid tissue after the first administration of radioiodine. Patients
      with higher iodine uptake in the neck had a tendency to receive higher activities
      of 131I. There were no statistically significant differences in age, sex, type of
      surgery, initial iodine uptake in the neck and administered radioiodine activity
      between those successfully ablated and those that were not. Patients receiving
      less than 3.7 GBq (100 mCi) tended to have lower iodine uptake (< 5% at 24 or 48
      h), but their rate of thyroid ablation was just as high as those given 3.7 GBq or
      more. In order to take advantage of this, we have formalized our approach by
      deriving guidelines to the empiric determination of radioiodine activity based on
      the iodine uptake in the neck. Among the 11 patients treated with lobectomy only,
      the ablation rate was 64%. Although this was not significantly lower than for
      other forms of surgery, we continue to recommend completion thyroidectomy for
      this group of patients, if the goal of treatment is to ablate all thyroid tissue.

PMID- 7820408
TI  - Case report: benign urachal neoplasm.
AB  - Benign urachal neoplasms have been rarely reported. We describe a case of a large
      benign mesenchymal neoplasm (21 x 19 x 14 cm) arising from the urachus, with
      imaging by computed tomography and ultrasound.

PMID- 7820409
TI  - Case report: saccular aneurysm of the intraorbital ophthalmic artery.
AB  - A saccular aneurysm of the intraorbital portion of the ophthalmic artery is
      extremely rare. We report this entity in a 54-year-old man who also had a dural
      arteriovenous malformation (AVM) at the base of the anterior cranial fossa. The
      aneurysmal formation at this unusual site may be explained by a haemodynamic
      stress that derived from the presence of the dural AVM.

PMID- 7820410
TI  - Case report: pedicular cleft associated with bilateral pars interarticularis
      defects and transverse process hypoplasia of a fifth lumbar vertebra.
AB  - The rare anomaly of cleft pedicle co-existing with bilateral pars
      interarticularis defects and ipsilateral transverse process hypoplasia of a
      lumbar vertebra is described in a 39-year-old male presenting with chronic low
      backache. The importance of recognizing pedicular clefts as congenital anomalies
      and distinguishing them from fractures or destructive processes is emphasized,
      and the relationship of pedicular clefts to hypoplastic or absent pedicles is
      discussed.

PMID- 7820411
TI  - Case report: mesenteric lymph node cavitation, an unusual complication of coeliac
      disease.
AB  - We present a case of mesenteric lymph node cavitation diagnosed by computed
      tomography. This is an unusual but recognized complication of coeliac disease
      associated with splenic atrophy.

PMID- 7820412
TI  - Case of the month: a nasty shock on awakening.

PMID- 7820413
TI  - Mesenteric arterial rupture following blunt abdominal trauma: demonstration by
      computed tomography.

PMID- 7820414
TI  - The long-term results of treatment of urinary stones.

PMID- 7820415
TI  - The first record of lithotripsy, in the early Byzantine era.

PMID- 7820416
TI  - The effects of sodium citrate and oral potassium citrate on urease-induced
      crystallization.
AB  - OBJECTIVES: To study the effects of citrate on urease-induced crystallization in
      human urine. MATERIALS AND METHODS: Urine samples were collected from seven
      healthy volunteers with no history of urinary tract infection or stone disease.
      Citrate was removed from the urine samples by decomposition with citrate lyase.
      Citrate was then added to the urine in increasing concentrations. Oral potassium
      citrate was given to the volunteers and their urine was collected. The samples
      were incubated with urease and the crystallization induced was observed by the
      Coulter counter technique, by using an optical microscope and by precipitated
      material analysis. RESULTS: The initiation of crystallization was markedly
      delayed by both the addition of citrate to the urine and after the ingestion of
      citrate. Crystal growth and the resulting precipitation of both calcium and
      magnesium showed a concentration-dependent reduction when citrate was added up to
      a concentration of 4 mM. Crystal growth and precipitation of calcium and
      magnesium were also significantly decreased by oral citrate intake. CONCLUSION:
      Citrate added to the urine or taken orally markedly delays urease-induced
      crystallization in human urine.

PMID- 7820417
TI  - Renal parenchyma-sparing surgery as conservative treatment of renal cell
      carcinoma.
AB  - OBJECTIVE: To evaluate the role of parenchyma-sparing surgery in patients with
      renal cell carcinoma (RCC). PATIENTS AND METHODS: Between 1965 and 1990, 34
      patients with RCC underwent renal parenchyma-sparing surgery. There were 22 men
      and 12 women with a mean age of 62 years (range 40-89). Ten patients underwent
      enucleation (Group A), 15 partial nephrectomy (Group B), and nine a combination
      of procedures (Group C). Conservative surgery was performed in the presence of a
      normal contralateral unit in four patients (12%). RESULTS: Five patients
      developed local recurrence. Metastases appeared in six patients (18%) from 12 to
      58 months post-operatively. Adequate renal function was obtained in 32 of the 34
      patients. The mean follow-up for all patients was 64.6 months overall, 75.6
      months for group A, 64.1 months for group B and 53.4 months for group C. The 3
      and 5 year probabilities of survival for all patients were 77.8% and 69.5%
      respectively. The probabilities of 3 and 5 year survival were 80% for group A,
      80% for group B and 71.4% and 57.1% for group C. CONCLUSION: Enucleation and
      partial nephrectomy are both viable options in the management of solitary or
      bilateral RCC, as there is no decline in effective tumour control and prognosis.
      Larger groups and longer follow-ups are needed to assess the role of renal
      parenchyma-sparing surgery more definitively.

PMID- 7820418
TI  - Partial nephrectomy for incidental renal cell carcinoma.
AB  - OBJECTIVE: To evaluate the role of nephron-sparing surgery in patients with
      incidental renal cell carcinoma and a normal contralateral kidney. PATIENTS AND
      METHODS: A total of 230 patients underwent curative surgery for unilateral renal
      cancer between 1979 and 1991. Of these, 41 had a partial nephrectomy. The numbers
      of patients who underwent partial or radical nephrectomy over the course of the
      study are compared. RESULTS: The number of partial compared to total
      nephrectomies increased from 8% in 1979-84, to 20% in 1984-88 and 30% in 1989-91.
      This reflected increased detection of incidental renal tumours by radiological
      imaging. The local recurrence rate in those patients who underwent partial
      nephrectomy was 2% and survival was 95%, with an average follow-up of 3 years
      (range, 2-13). CONCLUSION: Nephron-sparing excision of small, incidental renal
      tumours achieved comparable early results to radical nephrectomy.

PMID- 7820419
TI  - The effects of acute and chronic JJ stent placement on upper urinary tract
      motility and calculus transit.
AB  - OBJECTIVE: To determine the pathophysiological changes in upper urinary tract
      motility and calculus transit which may occur following JJ stent insertion.
      MATERIALS AND METHODS: The acute and chronic effects of JJ stent placement were
      studied in 24 canine renal units. Intrarenal and intraureteric pressures and
      motility were measured, in addition to transit times for complete passage of
      synthetic calculi from the upper ureter into the bladder. RESULTS: Acute effects
      included raised renal intrapelvic pressure, reduced pelvic and ureteric motility
      and delayed calculus transit time. Prolonged JJ stent placement was associated
      with return of intrapelvic pressure to normal but persistent changes in both
      renal and ureteric motility and also calculus transit time. CONCLUSION: In situ
      JJ stents impair upper urinary tract motility and experimental calculus transit
      time and may delay passage of ureteric calculi or calculus fragments following
      extracorporeal shock wave lithotripsy.

PMID- 7820420
TI  - The effects of various indwelling JJ stents on renal pelvic pressure and renal
      parenchymal thickness in the pig.
AB  - OBJECTIVE: To determine whether indwelling JJ stents significantly alter renal
      pelvic pressure and consequently have deleterious effects on renal function.
      MATERIALS AND METHODS: Thirteen piglets were used totalling 26 renal units. Using
      an open, sterile surgical procedure, 23 renal units were stented with 6 F JJ
      catheters of eight different types: three renal units were not stented and served
      as controls. Intra-pelvic pressure values during diuretic stress were measured
      before and after 6 weeks of intubation. The kidneys were then removed and sent
      for pathological evaluation of renal parenchymal thickness. RESULTS: A marked
      increase in intra-pelvic pressure values was found in two of the 19 stented renal
      units suitable for this measurement. A significant reduction (more than one third
      with respect to the control values) in renal parenchymal thickness was found in
      six of the 21 stented renal units suitable for this measurement, three of which
      had been intubated with a Cook polyurethane stent and three with an Angiomed
      Puroflex stent. CONCLUSION: In the present experimental study some JJ stents
      seemed to cause long-lasting changes in renal pelvic pressure and consequently to
      have deleterious effects on renal function. Although experimental findings are
      not always fully related to clinical practice, a knowledge of the potential
      effects of these prostheses is essential to minimize complications related to
      their use.

PMID- 7820421
TI  - Beta haemolytic group A streptococci causing urinary tract infection.
AB  - OBJECTIVE: To describe the clinical and laboratory findings in patients with
      Group A streptococci (GAS) bacteriuria. PATIENTS: Patients with GAS bacteriuria
      seen in a tertiary care hospital in southern India between 1988 and 1993 were
      identified. Data were collected from the hospital records. RESULT: GAS were
      isolated from 15 women and 11 men. Clinical data were available for 24 of these.
      The condition presented as asymptomatic bacteriuria (nine patients), dysuria or
      frequency (12), and fever without localizing signs (three). All infections
      occurred in individuals with systemic or local conditions predisposing to urinary
      tract infection. All patients responded well to antimicrobial therapy.
      CONCLUSION: GAS bacteriuria is rare and occurs only in individuals with other
      predisposing conditions. Patients with this infection respond well to therapy.

PMID- 7820422
TI  - The Mitrofanoff principle: expanding upon a versatile technique.
AB  - OBJECTIVE: To illustrate how the original principle of an appendicovesicostomy
      can be expanded upon and applied successfully to numerous urological conditions
      utilizing a variety of surgical techniques. MATERIALS AND METHODS: Over the 8
      year period 1985-1993 the Mitrofanoff principle was utilized 105 times in 100
      consecutive patients. Seven different types of catheterizing conduit were
      constructed in conjunction with six varieties of urinary reservoir for patients
      falling into one of seven different categories of uropathy. RESULTS: At a median
      follow-up of 30 months, the continence rate for patients was 91%. The re
      operation rate for conduit complications was 33%. Neither continence rates nor
      complications specific to the Mitrofanoff were related to the underlying
      uropathy, the type of conduit constructed, the urinary reservoir employed, and
      the patient's age at surgery. CONCLUSION: The Mitrofanoff principle of continent
      urinary diversion is a versatile technique with a predictable success rate
      applicable to a wide variety of urological conditions. Patients and surgeons
      should be aware of the significant rates of revision required on the
      catheterizing conduit to enable continence to be ultimately achieved.

PMID- 7820423
TI  - Continent urinary diversion using the Mitrofanoff principle.
AB  - OBJECTIVE: To review the clinical and symptomatic outcome of patients undergoing
      cystectomy and continent urinary diversion using the Mitrofanoff principle.
      PATIENTS AND METHODS: There were seven men and five women (median age 62 +/- 21
      years: range 21-79). The underlying diagnoses were: bladder carcinoma (8),
      neuropathic bladder disease (1), bladder exstrophy (1), tuberculosis (1) and
      interstitial cystitis (1). An ileo-caecal segment was used for construction of
      the reservoir. The appendix was used as a catheterizable conduit in 11 patients
      and a narrowed ileal tube in one patient. Symptomatic outcome was assessed by
      using a modified Visick grading. The median follow-up period was 15 +/- 10 months
      (range 6-39). RESULTS: The median hospital stay was 22 days. There were no post
      operative deaths, but major post-operative complications developed in three
      patients and included intra-abdominal lymphocele (1), intra-abdominal abscess
      formation (1) and prolonged ileus (1). In the late post-operative period (> 30
      days), four patients developed stenosis of the mucocutaneous junction and
      required dilatation. The overall symptomatic outcome was satisfactory in 11
      patients. There were no deaths in the peri-operative period and none of the
      patients has since required revision. Urinary continence was achieved in all 12
      patients during the day. One patient reported minimal, occasional leakage at
      nights. The median catheterization interval was 4 +/- 1 hours during the day
      (range 3-5) and 7 +/- 1 hours at night (range 6-9). CONCLUSION: Our experience
      with the Mitrofanoff procedure has been limited to a small number of patients.
      Despite this, the clinical outcome of the procedure was satisfactory. The
      procedure potentially offers an effective continence mechanism with acceptable
      post-operative morbidity.

PMID- 7820424
TI  - Autoaugmentation gastrocystoplasty: early clinical results.
AB  - OBJECTIVE: To assess the urodynamic and clinical outcome of five patients
      following an autoaugmentation gastrocystoplasty. PATIENTS AND METHODS: Four
      patients, two boys and two girls aged between 8 and 16 years, with a neuropathic
      bladder and incontinence, and one boy, aged 16 years, with an ileal conduit were
      included in the study. The bladder augmentation technique combined
      autoaugmentation and the addition of a demucosalized patch of gastric muscle to
      the created bladder diverticulum. RESULTS: All patients have improved bladder
      function, although one may require further surgery. Three had temporary
      difficulty tolerating full meals. CONCLUSIONS: This new technique seems to have a
      place in the management of the neuropathic bladder, but further laboratory study
      and cautious clinical application is required to ascertain its role in bladder
      augmentation.

PMID- 7820425
TI  - Evaluation of augmentation cystoplasty in childhood with reference to vesico
      ureteric reflux and urinary infection.
AB  - OBJECTIVES: To assess the non-operative treatment of vesico-ureteric reflux in
      patients with abnormal bladder compliance, to determine whether reduction in
      storage pressure by augmentation leads to cessation of reflux and whether
      symptomatic urinary tract infection worsens or renal function deteriorates if
      reflux continues after augmentation and clean intermittent catheterization (CIC).
      PATIENTS AND METHODS: Thirty-nine children (17 boys, 22 girls) who underwent clam
      ileocystoplasty over a 5-year-period were evaluated. The mean age at operation
      was 9.7 years (range 1.5-17.5). Pre-operative assessment included renal imaging
      and slow fill video-cystometry. Vesico-ureteric reflux, if present, was graded I
      V. The frequency and severity of symptomatic urinary tract infections were
      recorded. Cystometry was performed 6 months after reconstruction. Storage
      pressures below 20 cm saline were regarded as safe. The mean follow-up was 3.3
      years (range 10 months-6.1 years). RESULTS: Of the 17 renal units assessed for
      the outcome of reflux, 11 stopped reflux and one showed a lower grade. No patient
      showed worsening of upper tract dilatation or progressive renal scarring. Thirty
      seven patients (95%) had symptomatic urinary tract infection pre-operatively.
      Following bladder augmentation, clean intermittent catheterization and
      trimethoprim prophylaxis, seven continued to have symptomatic infection.
      CONCLUSIONS: Augmentation cystoplasty is effective in resolving reflux in a
      majority of the patients. This is achieved by reducing storage pressures to below
      20 cm saline and emptying the bladder regularly by CIC. There is also a reduction
      in the incidence and severity of symptomatic urinary tract infections. Even when
      reflux persists there is no evidence of deterioration of the upper tracts or
      progressive renal scarring.

PMID- 7820426
TI  - Urodynamic and clinical follow-up of 28 children after gastrocystoplasty.
AB  - OBJECTIVES: To determine the efficacy of gastrocystoplasty in creating a large
      and compliant urinary reservoir. PATIENTS AND METHODS: Twenty-eight children (14
      boys, 14 girls), with a median age of 9 years (range 4-17), were evaluated before
      and for a median of 2 years and 5 months after gastrocystoplasty. Evaluation
      included urodynamic and renal function studies and a survey of their post
      operative complications and their sense of well-being. Renal function was
      assessed by ultrasound and serum creatinine, and electrolytes were measured.
      RESULTS: After gastrocystoplasty bladder size increased, compliance improved,
      hydronephrosis decreased or was stable, and renal function remained stable. There
      were minimal complications and the children's subjective impression of their well
      being was markedly improved. CONCLUSION: Gastrocystoplasty, using our surgical
      technique, is a reliable method of creating a large and compliant urinary
      reservoir. Advantages include the absence of clinical urinary tract infections,
      the absence of mucus and the preservation of renal function. Complications, such
      as haematuria, dysuria and hypochloraemic alkalosis, might be avoided by
      excluding the antrum from the gastrocystoplasty, maintaining the child on a
      normal salt-containing diet, employing catheterization or buffering the urine in
      children with normal urethral sensation.

PMID- 7820427
TI  - Written consent about sexual function in men undergoing transurethral
      prostatectomy.
AB  - OBJECTIVE: To review the written recording of consent about possible sexual
      dysfunction after transurethral resection of the prostate (TURP), and the
      incidence of sexual dysfunction in sexually active men after TURP, from a large
      scale audit of transurethral prostatectomy held in 12 hospital sites in the
      Northern Region. PATIENTS AND METHODS: Over an 8-month period data were collected
      from 12 separate hospital sites within the Northern Region by two independent
      nurse co-ordinators who travelled to each of the sites. Information was gathered
      from medical records, operation lists and theatre books using a standard
      proforma. The Nottingham Health Profile (NHP) was used as a quality of life
      instrument in a subgroup of patients who were asked about sexual function before
      and after operation. RESULTS: Advice about retrograde ejaculation was recorded
      infrequently, with only 30% of case notes including a statement about this (inter
      site variations 0-78%). The mean age of patients in whom a written record was
      made was lower (70 [0.44 SEM] years) than those in whom there was no recording
      (72 [0.25] years; P < 0.001), but marital status did not appear to be a
      significant factor. No significant differences in NHP were found comparing men
      who did or who did not have written evidence about consent regarding retrograde
      ejaculation. In addition, in a subset of men who had been asked pre-operatively
      about sexual function, no significant differences were found in overall NHP
      measurements in those who did or who did not develop retrograde ejaculation. In
      men who were sexually active before operation, the incidence of major sexual
      problems, impotence and retrograde ejaculation were 12%, 11% and 24%
      respectively. CONCLUSION: The incidence of sexual dysfunction following TURP in
      this audit concurred with previously reported studies (4-40%), but despite this
      most urologists in our audit were not recording that they had advised their
      patients about this possible outcome.

PMID- 7820428
TI  - Corpus cavernosal relaxation in impotent men.
AB  - OBJECTIVE: To investigate smooth muscle responsiveness in isolated preparations
      of corpus cavernosum from men with vasculogenic impotence. PATIENTS AND METHODS:
      Biopsies of corpus cavernosum were obtained from 63 men undergoing penile
      surgery. These included a control group of eight men (mean age 59 years, range 38
      82) undergoing penile amputation for carcinoma, 47 men with vasculogenic
      impotence (mean age 58, range 36-72) who were further sub-divided into arterial
      (n = 9), venous (n = 24) or mixed arterial/venous (n = 14) impotence according to
      the results of pre-operative haemodynamic investigation, and eight men with non
      vasculogenic impotence (mean age 49 years, range 34-66). Smooth muscle
      contractile responses to alpha-adrenoceptor activation and relaxant responses to
      stimulation of intrinsic nerves and exposure to papaverine and sodium
      nitroprusside were recorded in tissue strips prepared from the biopsies.
      Morphology was assessed histologically using haematoxylin and eosin staining of
      tissue sections together with immunocytochemical labelling of intrinsic nerves.
      RESULTS: Nerve-evoked relaxation was markedly impaired in tissue from men with
      venous or mixed arterial/venous impotence. A lesser degree of impairment was
      found in tissue from men with arterial impotence alone. Tissue from men with all
      types of vasculogenic impotence also showed a decreased contractile response to
      alpha-adrenoceptor stimulation. The magnitude of relaxant responses to papaverine
      and sodium nitroprusside in the vasculogenic group was similar to that of the
      control. There were no differences in smooth muscle content or nerve density
      between the vasculogenic group and the control. In the non-vasculogenic group
      responses to relaxant nerve stimulation, alpha-adrenoceptor activation and
      relaxant drugs were similar to those of the control. Nerve density in this group
      was similar to the control but smooth muscle content was reduced. CONCLUSIONS:
      The results of this study demonstrate a functional impairment of smooth muscle
      contractility and neurogenic relaxation in corpus cavernosum from impotent men
      with abnormal penile haemodynamics. Altered smooth muscle responsiveness is
      likely to be a factor in the aetiology of impotence in such men and may
      contribute to the relatively poor results of vascular surgery for impotence.

PMID- 7820429
TI  - Preliminary report--combined surgical and radiological penile vein occlusion for
      the management of impotence caused by venous-sinusoidal incompetence.
AB  - OBJECTIVES: To combine surgical and radiological penile vein occlusion therapy in
      the treatment of patients with venogenic impotence, to try to improve on the
      results of either treatment used separately. PATIENTS AND METHODS: Fourteen
      patients, with a mean age of 46 years (range 25-71), with pure venous-sinusoidal
      impotence were treated by surgical ligation of accessible veins and embolization
      of surgically inaccessible veins. The preliminary results over a follow-up period
      of at least 8 months are reported for each patient. RESULTS: Venous embolization
      was considered complete in 11 patients. Overall, 13 had improved erectile
      function. Post-operatively, eight patients developed spontaneous erections and
      four (aged < 40 years) have maintained this for 8-24 months. CONCLUSION: Combined
      surgery and radiology treats the end result of the failure of the sinusoidal
      smooth muscle to relax. Although some patients, the majority of whom are young
      (aged < 40 years), will achieve short-term benefit, all individuals need to be
      fully counselled with regard to the likelihood of long-term benefit before
      undergoing this invasive method of treatment.

PMID- 7820430
TI  - Peyronie's disease and congenital penile curvature: long-term results of
      operative treatment with the plication procedure.
AB  - OBJECTIVE: To evaluate the results of plication of the tunica albuginea in
      patients with a curved penis. PATIENTS AND METHODS: Twenty-two men with
      congenital penile curvatures and 33 men with acquired penile curvatures were
      treated by the plication technique. Their files were studied and all patients
      underwent a follow-up interview and were physically examined. The mean age of the
      patients with congenital penile curvatures was 25.7 (range 17-58) and that of the
      men with acquired penile curvatures was 54.4 (range 28-67). The mean length of
      follow-up was 42 months. RESULTS: The mean angle of deviation in relation to the
      longitudinal axis was 48.2 degrees in the congenital curvatures and 63.3 degrees
      in the acquired curvatures. All congenital curvatures were corrected
      successfully, i.e. the penis was straight and satisfactory intercourse was
      possible. Slight shortening of the penile shaft was noticed by eight patients,
      but none was concerned about this finding. Pre-operatively, 12 of 33 patients
      with acquired curvature were unable to have intercourse because of the
      combination of decreased rigidity and abnormal curvature. Of these patients,
      three were able to have satisfactory intercourse post-operatively. Most of the
      nine patients with a poor result were known pre-operatively to have adverse
      factors affecting erectile function. Of the 21 patients who were only able to
      have intercourse with difficulty preoperatively, intercourse was easier and more
      satisfactory in 18 and more difficult in three post-operatively. Pre-operative
      pain with erection improved in all patients. Complications were mild. Shortening
      concerned only two patients with recurrent Peyronie's disease after re-operation.
      CONCLUSION: Plication of the curved penis is a relatively simple, save and
      effective procedure.

PMID- 7820431
TI  - Congenital and acquired curvature of the penis treated surgically by plication of
      the tunica albuginea.
AB  - OBJECTIVE: To evaluate the effectiveness of plication surgery for patients with
      congenital and acquired curvature of the penis. PATIENTS AND METHODS: Forty-eight
      patients with congenital curvature of the penis and 57 with induratio penis
      plastica were treated by plication of the tunica albuginea. Their average age was
      23 and 56 years, respectively. The operation was performed under local
      anaesthesia, using 2/0 Prolene and a specially designed suture. The average
      observation time in the two groups was 24 and 20 months, respectively. RESULTS:
      Nineteen per cent of patients in the first group and 8% in the second group
      reported normal intercourse pre-operatively. Post-operatively, the numbers
      increased to 81% and 82%, respectively, and all were able to perform intercourse.
      Although 18-19% experienced slight discomfort, mostly related to the cut ends of
      the suture, this minor problem was accepted by all. Five patients needed more
      than one operation. No impotence was recorded post-operatively and no patient
      complained of reduced sensibility of the skin. CONCLUSION: Satisfactory results
      were obtained with the plication technique in the first 105 patients. Since the
      follow-up study was completed more than 2 years ago, another 70 patients have
      been treated by the same procedure.

PMID- 7820432
TI  - The preventive role of chemical sympathectomy on contralateral testicular hypoxic
      parameters encountered during unilateral testicular torsion.
AB  - OBJECTIVE: To evaluate the effect of chemical sympathectomy on lactic acid and
      hypoxanthine concentrations in both testes during unilateral testicular torsion
      in a rat experimental model. MATERIALS AND METHODS: Four groups, comprising 10
      rats each, were studied. Group I was the control group, Group II rats received a
      placebo and underwent unilateral testicular torsion, Groups III and IV received
      guanethidine monosulphate and 6-OH-dopamine hydrobromide respectively, and
      underwent unilateral testicular torsion. The levels of lactic acid and
      hypoxanthine in both testes were measured. RESULTS: In rats in Group II the
      levels of lactic acid and hypoxanthine in both testes were significantly elevated
      when compared to the control group. In the groups of rats that had undergone
      chemical sympathectomy, the levels of lactic acid and hypoxanthine were
      significantly decreased in the contralateral testes compared to rats in Groups I
      and II. CONCLUSION: Chemical sympathectomy prevents the elevation of lactic acid
      and hypoxanthine levels in the contralateral testis of rats with unilateral
      testicular torsion. Therefore, we conclude that contralateral testicular damage
      during unilateral testicular torsion may result through a reflex activating
      sympathetic system.

PMID- 7820434
TI  - Control of torrential haemorrhage of the vena cava using Foley catheters.

PMID- 7820433
TI  - Biochemical analysis of tunica vaginalis fluid in patients with or without
      idiopathic hydroceles.
AB  - OBJECTIVE: To establish the differences, if any, between the biochemical
      composition of idiopathic hydrocele fluid and the fluid normally present in the
      tunica vaginalis. PATIENTS AND METHODS: Aspiration and sclerotherapy of 37
      idiopathic hydroceles from patients who presented to this urology clinic were
      performed. The biochemical content of the fluid was compared with that of the
      tunica vaginalis fluid from a small group of controls (n = 8), taken from
      patients undergoing orchidectomy for carcinoma of the prostate. RESULTS:
      Differences in several measurements were recorded; in particular, there were
      significantly higher concentrations of calcium, albumin, total protein and
      creatine-kinase in the hydrocele group. The levels of potassium, aspartate
      transaminase, alanine transaminase and alkaline phosphatase were significantly
      lower in the hydrocele group. CONCLUSION: Whether these differences have a role
      in the causation of an idiopathic hydrocele is, at this stage, speculative. A
      similar study on a larger scale would probably be more conclusive.

PMID- 7820435
TI  - Repair of the suspensory ligament of the penis: an important step in the
      transpubic approach.

PMID- 7820436
TI  - Purplish penile papule as a presenting sign of Kaposi's sarcoma.

PMID- 7820437
TI  - Ultrasonographic diagnosis and surgical enucleation of an epidermoid cyst of the
      testis.

PMID- 7820438
TI  - Primary classic Kaposi's sarcoma of glans penis--appearance on magnetic resonance
      imaging.

PMID- 7820439
TI  - Ectopic vasal insertion into the posterior urethra.

PMID- 7820440
TI  - Clitoral metastasis secondary to transitional cell carcinoma of the bladder.

PMID- 7820441
TI  - Renal leiomyoma.

PMID- 7820442
TI  - Left varicocele and ejaculatory duct obstruction: successful treatment of patient
      with infertility.

PMID- 7820443
TI  - Epidermal cyst presenting as an intrascrotal tumour.

PMID- 7820444
TI  - Simultaneous emphysematous cystitis and gangrenous cholecystitis. A case report.

PMID- 7820445
TI  - Adverse effects of short-term (up to 2 months) urinary catheterization.

PMID- 7820446
TI  - Iatrogenic ascent of the testis: an underrecognized complication of inguinal
      hernia operation in children.

PMID- 7820447
TI  - Endo-balloon rupture and stenting for pelvic-ureteric junction obstruction.

PMID- 7820448
TI  - Urinary continence after reconstruction of classical bladder exstrophy.

PMID- 7820449
TI  - Definition of dysuria.

PMID- 7820450
TI  - Liposomes for protein delivery: selecting manufacture and development processes.
AB  - The use of liposomes as protein carriers has been investigated for a number of
      possible potential applications in pharmaceutical formulations. These are for
      sustained release to improve adjuvancy for vaccine development, protein
      absorption enhancement, and drug targeting carriers and as vehicles for
      administration of hydrophobic compounds. The majority of current liposomal
      protein formulations are still in various preclinical research stages, with
      relatively little known or reported human clinical findings to date. There are
      still pending challenges to creating commercially stable and bioactive protein
      formulations with lipids. In addition to lipid developmental issues, because the
      stability of proteins may be affected by many physical or chemical manipulations,
      the choice of manufacturing designs for liposomal incorporation becomes somewhat
      more complex. For this reason, solvent-free vesicle procedures should be the
      primary approach to the preparation of protein-based formulations. In this regard
      a variety of recently reported methods are discussed. The advantages or
      disadvantages of these procedures are compared to those of procedures involving
      solvents. Consideration to large-scale manufacturing and protein recovery issues
      is also given.

PMID- 7820451
TI  - Liposomes as immunoadjuvants and vaccine carriers: antigen entrapment.
AB  - Successful use of liposomes as immunological adjuvants in vaccines requires
      simple, easy to scale up technology capable of high-yield antigen entrapment.
      Recent work from this laboratory has led to the development of techniques that
      can generate liposomes of various sizes containing soluble antigens such as
      proteins or particulate antigens such as whole, live, or attenuated bacteria or
      viruses. Entrapment of proteins is carried out by the dehydration-rehydration
      procedure, which entails freeze-drying of a mixture of "empty" small unilamellar
      vesicles and free antigens. Upon rehydration, the large multilamellar vesicles
      that are formed incorporate up to 80% of the antigen used. When such liposomes
      are microfluidized in the presence of nonentrapped material, their size is
      reduced to about 100 nm in diameter, with much of the originally entrapped
      antigen still associated with the vesicles. A similar technique applied to the
      entrapment of particulate antigens (e.g., Bacillus subtilis spores) consists of
      freeze-drying giant vesicles (4-5 microns in diameter) in the presence of spores.
      On rehydration and sucrose gradient fractionation of the suspension, up to 27% of
      the spores used are associated with generated giant liposomes of similar mean
      size.

PMID- 7820452
TI  - Liposomes as carriers for vaccines.
AB  - A liposome vaccine formulation that has been successfully used in both animal
      immunization studies and clinical trials is described. Issues concerning the
      choice of components for the liposomal vaccine formulation are discussed,
      especially with respect to the lipid components and the adjuvant. A procedure is
      described for manufacturing liposomal vaccines using Good Manufacturing Practices
      as promulgated by the U.S. Food and Drug Administration. Quality control testing
      for clinical use is described, with particular emphasis on aspects relevant to
      liposomes. Utilization issues are discussed, including injection volumes, antigen
      and adjuvant doses, and routes of administration.

PMID- 7820453
TI  - Endocytosis and presentation of liposome-associated antigens by B cells.
AB  - B cells have limited endocytic capacity and are reported to endocytose and
      present liposome-encapsulated antigens poorly. B cells also endocytose soluble
      antigens poorly, except those for which their surface immunoglobulin is specific,
      which are taken up and presented efficiently. We present results indicating that,
      in vitro, B cells endocytose small liposomes bearing antigen with affinity for
      their surface immunoglobulin. Antigen encapsulated in liposomes targeted by
      antibody specific for surface immunoglobulin is presented to T cells as
      efficiently as specific antigen in soluble form. These studies provide a rational
      basis for the design of liposomes optimized to stimulate T-dependent B-cell
      responses.

PMID- 7820454
TI  - Liposome-mediated cytoplasmic delivery of proteins: an effective means of
      accessing the MHC class I-restricted antigen presentation pathway.
AB  - Different types of liposomes have been employed to deliver soluble antigen for
      processing and presentation in the major histocompatibility complex class I
      restricted pathway. Anionic pH-sensitive liposomes as well as cationic liposomes
      efficiently sensitize antigen-presenting cells for recognition by the class I
      restricted cytotoxic T lymphocytes (CTL). Cytoplasmic delivery of liposome
      entrapped antigen from an endocytic compartment allows the exogenous antigen to
      gain access to the class I presentation pathway. Cytoplasmic delivery, however,
      is probably not the only mechanism by which liposomes induce the class I
      restricted CTL priming in vivo. Macrophages play a central role in the processing
      of the liposome-encapsulated antigens. The processed antigen fragments are
      probably released by the macrophages and taken up by the nearby dendritic cells
      for antigen presentation. Collaboration between the two types of immune cells
      with the help of the appropriate costimulatory factors is the central theme for
      this hypothesis. In this case, the host immune system utilizes the similar
      mechanism for other membranous, particulate antigens to process and present the
      liposomal antigens.

PMID- 7820455
TI  - Immunoliposomes and PEGylated immunoliposomes: possible use for targeted delivery
      of imaging agents.
AB  - Liposomes can be made target-specific by immobilizing antibodies on their surface
      against characteristic components of target organ or tissue. Possible schemes of
      antibody immobilization on liposomes are briefly considered. The use of
      immunoliposomes for the targeted delivery of diagnostic and therapeutic agents
      within the cardiovascular system is discussed. Immunoliposomes are shown to be
      suitable carriers for targeting blood vessel injuries, lung endothelium, and
      myocardial infarction. The role of polyethylene glycol in the preparation of long
      circulation liposomes is investigated, and a hypothesis explaining the mechanism
      of polymer protective action in terms of physicochemical properties of diluted
      polymeric solutions is suggested. Polyethylene glycol-coated liposomes are
      investigated as possible carriers of imaging agents for gamma and MR
      visualization of different areas of interest in the body, including lymph nodes.
      The possibility of simultaneous immobilization of protective polymer and antibody
      on the liposome surface is proved, and the long-circulating targeted
      immunoliposomes are used for the targeted delivery of radiolabel to necrotic
      areas in rabbits with experimental myocardial infarction.

PMID- 7820456
TI  - Immunoliposomes in vivo.
AB  - Attachment of antibodies to the surface of liposomes was performed to confer
      specificity for a certain cell or organ expressing the targeted antigenic
      determinant. These so-called immunoliposomes are expected to be applied as
      targeted drug carriers. In this article, the literature concerning in vivo
      studies of the targeting of immunoliposomes to various sites in the body is
      reviewed. The anatomical, physiological, and pathological constraints and current
      progress are described. Moreover, perspectives on the therapeutic feasibility of
      this drug targeting system are discussed.

PMID- 7820457
TI  - Systemic targeting of liposome-encapsulated immunomodulators to macrophages for
      treatment of cancer metastasis.
AB  - The therapy of cancer is, in reality, the design of therapeutic strategies for
      therapy of metastatic disease. Metastases consist of unique subpopulations of
      tumor cells that are derived from the primary tumor, colonize distant target
      organs, and are able to subvert host immune responses, establish necessary
      angiogenesis, and obtain a sufficient nutrient supply while evolving to become
      autonomous from homeostatic mechanisms that function within normal,
      differentiated tissues. Attempts at eradication of metastases by conventional
      therapies have generally been unsuccessful due to genetic instability and
      heterogeneity of metastatic tumors; these properties lead to the emergence of
      tumor cells that are resistant to most conventional treatments. It may be
      possible to circumvent this heterogeneity by the activation of tissue macrophages
      to the tumoricidal state. Activated macrophages are able to kill tumor cells
      while sparing normal tissues, and efficient activation can be achieved by
      encapsulation of synthetic muramyl tripeptide analogues into multilamellar
      vesicles composed of phospholipids. Systemic administration of these liposome
      encapsulated compounds leads to tumoricidal activation of alveolar and peritoneal
      macrophages and eradication of established tumor metastasis in numerous animal
      tumor models, and this form of therapy is enhanced by combination with parenteral
      administration of cytokines. Phase III clinical trials of recurrent osteosarcoma
      are currently in progress. Modulation of the tumor microenvironment by activated
      macrophages may prove to be an additional modality in treatment strategies that
      combine the use of biological response modifiers with conventional therapies.

PMID- 7820458
TI  - Mucosal and enterocyte grafts in the intestine.

PMID- 7820459
TI  - Venous ulcer.

PMID- 7820460
TI  - Trauma in pregnancy.
AB  - Trauma is a major cause of maternal death in pregnancy. The pregnant woman who
      has been involved in an episode leading to her arrival in an accident and
      emergency department presents with specific problems that often require
      specialist attention. The correct initial management of such patients should not
      be beyond the capabilities of an average trauma team and such management is
      clearly taught as part of the Advanced Trauma Life Support course now available
      in the UK. This review outlines the physiological changes associated with
      pregnancy that become important during resuscitation and definitive care. It
      discusses the presentation and management of specific problems, and the safety-
      or otherwise--of commonly administered drugs. Only the initial resuscitation of
      the patient is considered; specialist obstetric care is beyond the scope of the
      article.

PMID- 7820461
TI  - Significance of aneuploidy.
AB  - Aneuploidy is a state of abnormal and highly variable DNA and chromosome content
      found in both hereditary disorders and human malignancy. For two decades flow
      cytometry has allowed a wide-ranging survey of aneuploidy in clinicopathological
      series. Although up to 75 per cent of all tumours analysed display aneuploidy,
      its value as a clinical marker of biological aggressiveness is still uncertain.
      New technologies promise to reveal more precisely the genetic and subchromosomal
      changes that constitute aneuploidy and contribute to the malignant phenotype in
      human tumours.

PMID- 7820462
TI  - Macrolides in roles beyond antibiotic therapy.
AB  - Erythromycin and other macrolides with a closely related structure are widely
      used antibiotics. Side-effects related to administration of such drugs are mostly
      gastrointestinal. The direct effect of erythromycin on gastrointestinal motility
      was studied; it was found to have a stimulatory effect proximally, on stomach and
      duodenal motility, with an apparent distal inhibition. Gastric emptying was
      accelerated by erythromycin via an antroduodenal coordination mechanism, an
      effect that has proved to be beneficial in surgical and medical conditions in
      which gastroparesis is a problem. Erythromycin is now used experimentally and
      clinically; it has been found to accelerate gastric as well as gallbladder
      emptying and to have an effect on the oesophagus. Analogues of erythromycin have
      been developed that have potent gastrointestinal activity but little or no
      antibacterial potential. Macrolides modulate the antibacterial action of
      neutrophils, with some action on the oxidative burst. Finally, two new macrolide
      immunosuppressants have been developed that compare favourably with traditional
      drugs.

PMID- 7820463
TI  - Clinical relevance of intraoperative embolization detected by transcranial
      Doppler ultrasonography during carotid endarterectomy: a prospective study of 100
      patients.
AB  - A study was performed to investigate the clinical significance of
      microembolization detected by transcranial Doppler ultrasonography (TCD) by
      determining the quantity and character of emboli and correlating these with
      neurological and psychometric outcome, fundoscopy, automated visual field testing
      and computed tomographic brain scans in 100 consecutive patients undergoing
      carotid endarterectomy. Embolization was detected in 92 per cent of successfully
      monitored operations. Most emboli were characteristic of air and not associated
      with adverse clinical outcome. However, more than ten particulate emboli during
      initial carotid dissection correlated with a significant deterioration in
      postoperative cognitive function. A relationship between persistent particulate
      embolization in the immediate postoperative period, and both incipient carotid
      artery thrombosis and the development of major neurological deficits was
      observed. Immediate intervention, based on TCD evidence of embolization, has the
      potential to avert neurological deficits resulting from particulate embolization.

PMID- 7820464
TI  - Surgical workload as a consequence of screening for abdominal aortic aneurysm.
AB  - A study was performed to evaluate the surgical workload that has resulted from
      screening an at-risk population for abdominal aortic aneurysm (AAA) and to
      forecast the likely workload from an established screening programme. Over an 8
      year period 8944 people aged 65-80 years were screened; 356 were found to have an
      AAA of 3 cm or greater in diameter. There were 288 outpatient consultations
      involving 171 patients, and 43 patients (4.8 per 1000 screened) had surgery
      during the study period. A fully operational screening programme for a population
      of 250,000, screening men and women at a rate of 2000 per year, would be expected
      to produce a surgical workload of nine or ten operations for AAA per year.
      Screening men only would increase this to 34 annually.

PMID- 7820465
TI  - Effect of an endovascular stent on healing of an end-to-end
      polytetrafluoroethylene-artery anastomosis in a canine model.
AB  - A canine model of end-to-end anastomosis between the iliac arteries and
      polytetrafluoroethylene grafts was developed; a self-expanding Wallstent was
      placed across one anastomosis. The opposite limb acted as a control. Animals were
      killed at 4 or 12 weeks. Sections were taken and the intimal thickness and
      luminal area calculated. At 12 weeks intimal thickness was significantly greater
      at anastomoses in control sections (P = 0.007), and at the interface between the
      proximal stent and graft in stented graft limbs (P = 0.01). Control graft limbs
      had significantly enhanced intimal thickness at the anastomotic level at 12 weeks
      compared with that at 4 weeks (P = 0.0002), while there was no such increase for
      the stented side. There was no significant difference in luminal area between
      control and stented graft limbs. Anastomotic neointimal hyperplasia in a canine
      graft-artery bypass model is modified by endovascular stenting.

PMID- 7820466
TI  - Pulse-generated run-off versus dependent Doppler ultrasonography for assessment
      of calf vessel patency.
AB  - Pulse-generated run-off (PGR) is an established technique in the assessment of
      calf vessel patency. Dependent Doppler ultrasonography is proposed as a fast and
      simple alternative. Twenty-six limbs with severe ischaemia were evaluated by PGR,
      dependent Doppler examination and intra-arterial digital subtraction angiography
      (DSA). PGR was performed and scored as previously described. Dependent Doppler
      ultrasonography was performed after 5 min of foot dependency and scored as for
      PGR. Angiograms were scored by an independent radiologist, who awarded 2 for a
      vessel widely patent to the ankle, 1 for a diseased vessel crossing the ankle and
      0 if no vessel was visualized. Of 78 calf vessels evaluated, 59 (76 per cent)
      appeared patent on PGR and dependent Doppler examination but only 33 (42 per
      cent) appeared patent to the ankle with intra-arterial DSA. There was very good
      agreement between PGR and dependent Doppler for detection of patent calf vessels
      (kappa = 0.93). Doppler signals were biphasic in six calf vessels on dependency
      and in 22 vessels with PGR. PGR and dependent Doppler ultrasonography detected 26
      vessels communicating with the pedal arch compared with seven detected
      angiographically. There was good agreement between PGR and dependent Doppler
      examination for diagnosis of the most suitable vessel for distal anastomosis
      (kappa = 0.80). The wide availability and simplicity of dependent Doppler
      ultrasonography mean that no patient with a critically ischaemic limb should be
      denied reconstructive surgery on the basis of angiographic findings alone.

PMID- 7820467
TI  - Patterns of reflux in recurrent varicose veins assessed by duplex scanning.

PMID- 7820468
TI  - Saphenous vein reflux without incompetence at the saphenofemoral junction.
AB  - Duplex ultrasonography was used to assess patients with primary varicose veins to
      determine whether varicosities of the long saphenous vein (LSV) occurred without
      saphenofemoral junction (SFJ) incompetence. Some 167 consecutive patients with
      the clinical diagnosis of primary varicose veins were investigated. Of 190 limbs
      with LSV reflux 63 had no SFJ incompetence, of which only five had incompetent
      perforators; these were midthigh perforators in two limbs and medial calf
      perforators in three. LSV reflux often occurs in the presence of a competent SFJ.
      This indicates that, in such circumstances, saphenofemoral ligation alone is
      unlikely to control varices associated with LSV reflux. It also suggests that the
      development of primary varicose veins may be an ascending rather than a
      descending phenomenon.

PMID- 7820469
TI  - Stripping of the long saphenous vein in the treatment of primary varicose veins.
AB  - Eighty-nine legs with long saphenous vein (LSV) reflux and saphenofemoral
      junction incompetence were treated by saphenofemoral ligation and multiple
      avulsions; patients were randomized to undergo additional stripping of the LSV
      from groin to upper calf (n = 43) or no additional treatment (n = 46). At a
      median of 21 months after surgery recurrence was evaluated by duplex
      ultrasonography, photoplethysmography, clinical examination and patient
      assessment. Fewer persisting incompetent LSVs in the calf were found (21 versus
      38) and median (interquartile range) photoplethysmographic refilling times were
      longer (20 (13-27) versus 14 (11-21) s) when the LSV was stripped than after
      saphenofemoral ligation alone (both P < 0.1). More patients were completely
      satisfied (65 versus 37 percent and were recurrence-free (65 versus 17 per cent)
      when the LSV had been stripped compared with saphenofemoral ligation alone (P <
      0.05 and P < 0.001 respectively). The addition of LSV stripping to saphenofemoral
      ligation and multiple avulsions results in a better overall outcome.

PMID- 7820470
TI  - Kidney retrieval from asystolic donors: a valuable and viable source of
      additional organs.

PMID- 7820471
TI  - Urine testing for acute lower abdominal pain in adults.

PMID- 7820472
TI  - Bradykinin, coronary artery disease and gastro-oesophageal reflux.
AB  - Gastro-oesophageal reflux and coronary artery disease frequently coexist.
      Stimulation of myocardial vagal receptors impairs lower oesophageal sphincter
      (LOS) function and may explain this link. This study examined the role of
      bradykinin, produced in increased quantities by the ischaemic myocardium, in
      activating this reflex. Thirteen dogs had patches soaked in bradykinin 100
      micrograms/ml and saline applied sequentially to the left ventricular epicardium.
      Eleven of these animals were further divided into two subgroups: group 1 animals
      (six dogs) had the above sequence repeated after obliteration of sympathetic
      afferent fibres with phenol and those in group 2 (five animals) underwent
      sequential intravenous and intra-atrial injection of bradykinin 0.2
      micrograms/kg. Epicardial bradykinin produced a fall in mean(s.e.m.) LOS tone
      from 13.3(1.3) to 6.0(0.5) sphinctometer units (P < 0.002), accompanied by a
      reduction in mean(s.e.m.) arterial pressure from 95(4) to 83(5) mmHg (P < 0.002).
      Destruction of sympathetic afferent fibres did not alter the LOS effect. Intra
      atrial, but not intravenous, bradykinin reproduced the LOS effect; this suggests
      a cardiac origin. Myocardial release of bradykinin may play a role in producing
      transient LOS relaxation, predisposing to gastro-oesophageal reflux.

PMID- 7820473
TI  - Prediction of recurrent bleeding after endoscopic haemostasis in non-variceal
      upper gastrointestinal haemorrhage.
AB  - Endoscopic haemostasis by injection of adrenaline was attempted in 135
      consecutive patients with active upper gastrointestinal bleeding. Initial
      haemostasis was obtained in 127 patients following injection of 5-15 ml 1:10,000
      adrenaline; eight patients in whom haemostasis was not achieved underwent
      immediate laparotomy. There was further haemorrhage in 25 patients, which was
      successfully treated by further injection of adrenaline in ten. Fifteen patients
      had major rebleeding requiring emergency surgery. Stepwise logistic regression
      analysis identified three factors that, taken together, were highly predictive of
      the need for surgery: pulse rate on admission, the position of the ulcer and
      whether the patient was obese. A scoring system was derived from the logistic
      analysis equation that was found to predict correctly the need for emergency
      surgery in 84 per cent of patients. In patients with a high probability of
      rebleeding surgery should be considered after initial endoscopic haemostasis and
      stabilization. In the majority of patients endoscopic treatment alone is
      sufficient for permanent haemostasis.

PMID- 7820474
TI  - Long-term results of highly selective vagotomy: a prospective study with
      implications for future laparoscopic surgery.
AB  - Between 1979 and 1984, 141 patients (110 men, 31 women) underwent highly
      selective vagotomy (HSV) by a standard open technique for duodenal ulcer. All
      patients had received preoperative treatment with full-dose H2-receptor
      antagonists. Some 107 of these patients underwent HSV for persistent relapse on
      withdrawal of H2-receptor antagonists (relapsing responders) and 30 because of
      non-response to such drugs. After 4 years of follow-up, non-responders were found
      to be more likely to have symptoms after operation (P < 0.001), but did not have
      a higher rate of recurrent ulceration. At a median of 11 (range 8-14) years after
      operation 126 patients were still alive; 115 (91 per cent) of these were followed
      up. Ten patients (9 per cent) were found to have had endoscopically proven
      recurrence and eight (7 per cent) still had symptoms without evidence of
      recurrence. The endoscopic recurrence rate and symptom rate at 11 years were no
      longer significantly different between relapsing responders and non-responders.
      The preoperative response to H2-receptor antagonist therapy does not help in
      predicting the likelihood of ulcer recurrence or long-term symptoms after HSV.
      Post-operative symptoms do not necessarily predict long-term ulcer recurrence.
      The long-term endoscopic recurrence rate after HSV is low and, if equally good
      results can be obtained laparoscopically, this will be an important and cost
      effective option in the management of duodenal ulcer.

PMID- 7820475
TI  - Surgical treatment of primary duodenal carcinoma: a personal series.
AB  - In a personal series, 22 patients (11 men, 11 women) of median age 60 (range 25
      81) years with primary duodenal adenocarcinoma underwent operation between 1979
      and 1993. Tumours arising from bile duct, ampullary or pancreatic tissue were
      excluded. Principal presenting symptoms were jaundice (12 patients), pain
      (seven), anaemia (six) and vomiting (six). A pre-existing villous adenoma was
      seen in 11 patients and adjacent duodenal dysplasia in 13. Sites of origin were
      mostly the second part of the duodenum (18 patients) but also the third and
      fourth parts (two each). Seventeen patients underwent 'curative' resection with
      one hospital death at 25 days; the 5-year survival rate thereafter was 40 per
      cent. Five patients who received palliative surgery survived for a median of 7
      months. Primary duodenal carcinoma is a distinct entity with a better prognosis
      than pancreatic cancer after radical resection. It favours the descending
      duodenum and is closely linked with villous adenoma and epithelial dysplasia.

PMID- 7820476
TI  - Reconstructive abdominal operations after laparostomy and multiple repeat
      laparotomies for severe intra-abdominal infection.
AB  - Between 1980 and 1993, 18 patients underwent formal laparotomy after laparostomy
      and healing of the peritoneal cavity by granulation. The majority (12 patients)
      were men and the median age was 47 (range 22-67) years. Intraabdominal infection
      following surgery for Crohn's disease (four patients) and necrotizing
      pancreatitis (six) was the most common primary condition requiring laparostomy. A
      total of 23 reconstructive operations were carried out on the 18 patients a
      median of 6 (range 1-18) months after laparostomy. The indication for surgery was
      for closure and/or resection of an enteric fistula in 13 patients. The site of
      the fistula included three gastric, two duodenal, 11 small bowel and seven
      colonic. A further four patients required operation for closure or refashioning
      of a stoma. Five patients subsequently required a second laparotomy: two for
      elective restoration of bowel continuity, two for recurrent fistula and one for
      an acute abdomen. After reconstructive surgery following laparostomy 16 patients
      were discharged home alive and well, one requiring home parenteral nutrition for
      short bowel syndrome. In contrast, the two oldest patients in the series died
      from multiple organ failure immediately after initial reconstructive surgery.
      Both had pre-existing medical problems and in neither was there evidence of
      further intra-abdominal infection after reconstruction.

PMID- 7820477
TI  - Use of coloured undergloves to detect glove puncture.

PMID- 7820478
TI  - Colonic second primary cancers in patients with index tumours of the head and
      neck.

PMID- 7820480
TI  - Genetic susceptibility to colorectal cancer in patients under 45 years of age.
AB  - A study was conducted to assess the genetic contribution to the development of
      colorectal cancer in young probands. Of 83 patients aged 45 years or under
      diagnosed with colorectal cancer in one health region over a 2-year period, 65 or
      their surviving next of kin were available for interview, from whom were obtained
      60 detailed and five limited family histories. Five families fulfilled the
      Amsterdam criteria and a further eight satisfied less strict criteria for
      hereditary non-polyposis colorectal cancer, a total of 20 per cent of the cohort.
      Eleven of these families came from the subgroup of 13 probands who had one or
      more first-degree relatives with colorectal cancer. Overall the relative risk of
      colorectal cancer in close relatives was 5.2 (P < 0.0001). This risk was highest
      for female relatives at 9.7 (P < 0.0001) and relatives of female probands at 6.7
      (P < 0.0001). This study highlights the importance of taking a family history in
      this group of patients. Screening by colonoscopy for all close relatives of young
      patients with colorectal cancer is recommended.

PMID- 7820479
TI  - Survival after peranal and abdominoperineal resection for rectal carcinoma.
AB  - The outcome of a consecutive series of 47 patients with rectal cancer treated by
      endoscopic transanal resection or peranal local excision was contrasted with that
      of 42 patients undergoing abdominoperineal resection. Surgery was considered
      curative for 35 and nine patients treated by abdominoperineal and peranal
      resection respectively (P < 0.001). Patients undergoing peranal excision were
      older than those treated by abdominoperineal resection (median 77 versus 69
      years, P < 0.01). The 5-year survival rate of patients undergoing peranal
      resection was 24 per cent compared with 33 per cent for those treated by the
      abdominoperineal procedure (P < 0.005). When surgery was palliative the survival
      rate after both procedures was the same. Survival after peranal excision was
      significantly poorer than that after abdominoperineal resection but this may be
      acceptable when the stage of disease and age of the patients are taken into
      account.

PMID- 7820481
TI  - Antegrade enemas for the treatment of severe idiopathic constipation.
AB  - The technique of appendicocaecostomy produces a continent catheterizable channel
      through which colonic washouts are given. This procedure was performed on six
      women of mean age 33.5 years with severe idiopathic constipation (mean stool
      frequency less than 1 per week) resistant to medical therapy. All patients had
      prolonged colonic transit times, three had evidence of obstructed defaecation and
      all had reduced or absent voluntary anal squeeze pressure. Patients found the
      appendicocaecostomy and catheterization acceptable, and symptoms of abdominal
      distension and pain resolved. All patients were able to initiate defaecation and
      evacuate the colon within 1 h of irrigation, and no patient had appreciable
      incontinence. Irrigation was necessary every 48-72 h. Adults with intractable
      constipation and pelvic floor weakness would be at risk of faecal incontinence
      after ileorectal anastomosis; it is in these patients that appendicocaecostomy
      has potential for the greatest benefit.

PMID- 7820482
TI  - Comparative audit of colorectal resection with the POSSUM scoring system.
AB  - Comparison of outcome after colorectal resection between different surgical units
      is difficult. Crude rates of morbidity and mortality may give a distorted picture
      as such rates fail to account for variations in case mix and physiological status
      of patients. The simple and validated scoring system POSSUM (Physiological and
      Operative Severity Score for enUmeration of Mortality and morbidity) was used to
      compare outcome after colorectal resection in two units. Consecutive series of
      patients who underwent colorectal resection in unit 1 (a university teaching
      hospital) or unit 2 (a district general hospital) were scored with the POSSUM
      system. Postoperative complications and 30-day mortality were recorded. In unit
      1, 66 patients underwent colorectal resection with a mortality rate of 6 per cent
      and a morbidity rate of 9 per cent. In unit 2 the rates of mortality and
      morbidity were 9 and 26 per cent respectively for 182 patients undergoing
      colorectal resection. However, application of POSSUM predicted a mortality rate
      of 5.2 per cent for patients in unit 1 and 9.8 per cent for those in unit 2 with
      predicted morbidity rates of 11.2 and 23.9 per cent respectively. Direct
      comparison of outcome between these two units would be misleading. Application of
      POSSUM allows more realistic comparative audit of colorectal resection.

PMID- 7820483
TI  - Pudendal neuropathy in patients with idiopathic faecal incontinence progresses
      with time.

PMID- 7820484
TI  - Plasma elastase in venous disease.
AB  - The plasma elastase level was measured as a marker of neutrophil degranulation in
      three groups, each of 15 patients, with uncomplicated varicose veins,
      lipodermatosclerosis (LDS) and venous ulceration. The values obtained were
      compared with those in age- and sex-matched control subjects. Significantly
      higher levels of elastase were found in all patient groups compared with
      controls: median 25.6 ng/ml for patients with uncomplicated varicose veins, 22.1
      ng/ml for those with LDS, 26.0 ng/ml for those with venous ulceration. There was
      no difference in neutrophil count between the patient and control groups. These
      results provide evidence of increased neutrophil degranulation in patients with
      venous disease. The finding of raised elastase levels in all three patient groups
      shows that this was not due solely to the inflammatory process characterizing LDS
      and venous ulceration.

PMID- 7820485
TI  - Role of lipid mediators in the pathogenesis of skeletal muscle infarction and
      oedema during reperfusion after ischaemia.
AB  - During revascularization of skeletal muscle lipid mediators are released that may
      have a role in the pathogenesis of reperfusion injury. This study investigated
      the efficacy of the lipid mediator antagonists U74500A (a lipid peroxidation
      inhibitor), GR32191 (a thromboxane A2 receptor antagonist) and SC41930 (a
      leukotriene B4 (LTB4) receptor antagonist) in altering muscle viability and
      oedema, in a rat hindlimb model of 6-h ischaemia and 4-h reperfusion. Study
      groups comprised normal, ischaemic (6-h ischaemia) and control rats, and animals
      receiving the lipid mediator antagonists. Ischaemia itself did not result in
      muscle oedema or necrosis but both occurred following reperfusion (P < 0.01).
      Muscle viability was preserved by all lipid mediator antagonists (P < 0.01 versus
      controls, P not significant versus normal and ischaemia), with the LTB4 receptor
      antagonist ameliorating limb oedema (P < 0.01 versus controls). These results
      demonstrate a role for lipid mediators in reperfusion injury and suggest that
      their antagonists might aid the management of acute limb ischaemia.

PMID- 7820486
TI  - Asymptomatic popliteal aneurysm: elective operation versus conservative follow
      up.
AB  - In a retrospective study 42 patients with asymptomatic popliteal artery aneurysm
      were followed without surgery to identify variables predicting the risk of
      complications. The mean aneurysm size was 3.1 cm. Abnormal ankle pulses were
      found in 18 of the 42 limbs in which an asymptomatic popliteal aneurysm was
      present. Follow-up was complete (mean 6.2 years). Twenty-five patients developed
      complications at a mean observation time of 18 months. As a result three lost the
      limb, eight had claudication, two needed a fasciotomy and one had a peroneal
      nerve palsy. The cumulative risk of developing complications during follow-up was
      24 per cent at 1 year, rising to 68 per cent at 5 years. Patients with absent
      ankle pulses and those already operated on for abdominal aortic aneurysm proved
      to be especially at risk. Patient survival appeared to be normal for the period
      of observation. It is concluded that asymptomatic aneurysm of the popliteal
      artery is a potentially dangerous lesion that may justify elective surgery; it is
      possible to select those at highest risk.

PMID- 7820487
TI  - Experience with brain biopsy in acquired immune deficiency syndrome-related focal
      lesions of the central nervous system.
AB  - Involvement of the central nervous system (CNS) in patients with acquired immune
      deficiency syndrome (AIDS) is an increasing clinical problem. The most common
      brain complications are toxoplasmosis (50-70 per cent), primary CNS lymphoma (20
      30 per cent) and progressive multifocal leucoencephalopathy (10-20 per cent).
      Almost two-thirds of these conditions can be treated, early diagnosis and therapy
      leading to survival with a good quality of life. Although clinical and
      neuroradiological criteria alone may have high predictive value, they are not
      sufficient to distinguish the broad spectrum of diseases reliably. Consequently,
      biopsy appears necessary for definite diagnosis in some cases. The potential role
      and timing of brain biopsy have been assessed. Twenty-four of 50 human
      immunodeficiency virus-seropositive patients with focal cerebral lesions were
      considered for biopsy between October 1991 and December 1992. Twelve underwent
      brain biopsy, seven stereotactic and five ultrasonographically guided. A
      diagnosis was achieved in 11 patients: six primary lymphoma, three progressive
      multifocal leucoencephalopathy, and one mycotic and one tuberculous abscess. Both
      techniques proved to be safe and reliable, with a 92 per cent diagnostic rate.
      These data confirm the usefulness of biopsy in patients with AIDS with its wide
      range of associated cerebral lesions that require different aggressive
      treatments. On the basis of this preliminary experience and reports in the
      literature, it is considered that brain biopsy is indicated for patients with
      focal enhancing cerebral mass lesions seen on computed tomography and magnetic
      resonance imaging who do not respond to an appropriate trial of empirical
      antitoxoplasmosis therapy and for those showing rapid clinical deterioration in
      whom imaging and serology do not suggest toxoplasmosis.

PMID- 7820488
TI  - Management of goitre in Pendred's syndrome.

PMID- 7820489
TI  - Breast cancer incidence, penetrance and survival in probable carriers of BRCA1
      gene mutation in families linked to BRCA1 on chromosome 17q12-21.
AB  - Eight breast cancer pedigrees with a high probability of containing individuals
      with the BRCA1 gene mutation (odds 79.2-99.9 per cent) were identified through
      genetic linkage analysis using probes located within q12-22 on the long arm of
      chromosome 17. Some 102 female relatives were successfully typed with one or both
      of adjacent markers D17S588 and D17S579, and 41 were probable non-BRCA1 mutation
      carriers. Of the remaining 61 women classified as probable BRCA1 carriers, breast
      cancer was diagnosed in 35. As expected from epidemiological segregation analysis
      studies, 13 of these had bilateral disease. Approximately two-thirds of women
      unaffected by malignancy and alive at the time of observation were non-BRCA1
      carriers. Lifetime disease penetrance of the BRCA1 gene was 88 per cent and this
      plateau was reached earlier (by age 65 years) than that estimated in segregation
      analysis. The survival curve of patients with breast cancer was less steep in
      BRCA1 gene carriers than that in the general population; 5-, 10- and 20-year
      survival rates unadjusted for non-cancer deaths were 83, 63 and 41 per cent
      respectively. The 5-year survival rate was significantly higher in BRCA1 carriers
      than that in an age-matched Scottish population (P < 0.05).

PMID- 7820490
TI  - Colomastology as a subspecialty of surgical oncology.

PMID- 7820491
TI  - Hypotension induced by haemorrhage impairs lower oesophageal sphincter function.
AB  - The effect of haemorrhage-induced hypotension on lower oesophageal sphincter
      (LOS) tone was studied in 11 adult mongrel dogs. Mean(s.e.m.) blood loss of
      760(66) ml, corresponding to 42 per cent of estimated blood volume, was
      associated with a significant fall in LOS tone (14.2(1.0) versus 7.2(0.6)
      sphinctometer units, P < 0.002). This was associated with a reduction in
      mean(s.e.m.) arterial blood pressure (99(7) versus 53(3) mmHg, P < 0.002) and
      heart rate (113(6) versus 106(5) beats per min, P = 0.06). Group 1 animals (n =
      6) received autotransfusion, restoring LOS tone to prehaemorrhage values. Dogs in
      group 2 (n = 5) were given intravenous erythromycin 4 mg/kg, which also restored
      LOS tone. This effect was transient, lasting a mean(s.e.m.) of only 67(7) min.
      Infusion of an equivalent volume of 0.9 per cent saline following cessation of
      the erythromycin effect restored LOS tone to control values although the animals
      remained hypotensive. Reduction in LOS tone with haemorrhage may be part of a
      vagal reflex mediated by myocardial afferent C fibres and may explain the high
      incidence of pulmonary aspiration in shocked patients.

PMID- 7820492
TI  - Long-term effects of postoperative total parenteral nutrition supplemented with
      glycylglutamine on subjective fatigue and muscle protein synthesis.
AB  - Seventeen patients undergoing elective open cholecystectomy were given
      conventional total parenteral nutrition either with (nine patients) or without
      (eight) glutamine supplementation of 20 g/day for 3 days after surgery and
      thereafter ordinary food for the following 27 days. Muscle protein synthesis, as
      assessed by the total concentration of ribosomes, decreased in control patients
      on day 3 following surgery and remained low on days 10, 20 and 30 (P < 0.05). In
      patients who received glutamine the total ribosome concentration was maintained
      on the third day after operation. Concurrently, the subjective feeling of fatigue
      increased on days 3 and 10 after surgery and the nitrogen balance was negative
      after operation in both groups, without any difference related to glutamine
      supplementation. Intravenous glutamine after surgery counteracts a decline in
      muscle protein synthesis only for as long as it is provided.

PMID- 7820493
TI  - Laparoscopic gastroplasty for morbid obesity.

PMID- 7820494
TI  - Percutaneous cystogastrostomy for chronic pancreatic pseudocyst.
AB  - During the years 1984-1992, 74 patients of mean age 45 (range 6-71) years with
      chronic pancreatic pseudocyst were treated by percutaneous cystogastrostomy. They
      comprised 45 men and 29 women. A diagnosis of chronic pancreatitis was verified
      in 55 patients (74 per cent); pain was the indication for treatment in all cases.
      The catheter was successfully placed at the first attempt in 68 patients (92 per
      cent). Immediate complications occurred in four patients (5 per cent); there have
      been none since 1986. Abscess formation was seen in eight patients (11 per cent).
      One patient died 4 days after the procedure from myocardial infarction giving a
      mortality rate of 1 per cent; no death has occurred since 1986. The mean
      observation time was 27 (range 0-108) months. Pain disappeared or decreased in
      almost 90 per cent of patients and weight gain was seen in 80 per cent. The
      method described is less traumatic than operation, and mortality and complication
      rates compare favourably with those seen after surgery; the results are at least
      as good.

PMID- 7820495
TI  - Herniography for occult hernia and groin pain.
AB  - In a prospective 3-year study herniography was used to assess patients with
      unexplained groin pain in whom clinical signs were inconclusive. Fifty-two
      patients were studied. No serious complications were observed. Twenty-two hernias
      were identified in 18 patients. The positive herniographic findings were
      confirmed at operation in 12 patients. Of 34 patients with a negative herniogram,
      none has developed a hernia. Pain settled spontaneously in 29 patients and five
      were referred to a pain clinic for further management.

PMID- 7820496
TI  - Method for treatment of large high rectovaginal fistula.

PMID- 7820497
TI  - Compartment syndrome in experimental chronic pancreatitis: effect of
      decompressing the main pancreatic duct.

PMID- 7820498
TI  - Multicentre audit of death from acute pancreatitis.

PMID- 7820499
TI  - Vascular endoscopy: useful tool or interesting toy.

PMID- 7820500
TI  - Occlusion of a femorofemoral crossover graft by external compression from a
      femoral hernia.

PMID- 7820501
TI  - Oesophagogastrectomy for carcinoma of the oesophagus and cardia.

PMID- 7820502
TI  - Effect of gastric resection, Roux-en-Y diversion and vagotomy on gastric emptying
      in the rat.

PMID- 7820503
TI  - Intravenous digital subtraction angiography versus computed tomography in the
      assessment of abdominal aortic aneurysm.

PMID- 7820504
TI  - Abdominal ultrasonography for the diagnosis of strangulation in small bowel
      obstruction.

PMID- 7820506
TI  - Preventing complications of laparoscopy.

PMID- 7820505
TI  - 'Second-look' laparoscopy in the management of acute mesenteric ischaemia.

PMID- 7820507
TI  - Variation in outcome of surgical procedures.

PMID- 7820508
TI  - Use of conventional instruments at laparoscopic surgery.

PMID- 7820509
TI  - Evaluation of the cost of laparoscopic and open cholecystectomy.

PMID- 7820510
TI  - Abdominal wall metastases following laparoscopy.

PMID- 7820511
TI  - Endothelial cell seeding of vascular grafts: status and prospects.

PMID- 7820512
TI  - Carotid endarterectomy without a temporary indwelling shunt: results and analysis
      of back pressure measurements.
AB  - A consecutive series of 342 carotid endarterectomies for cerebrovascular
      insufficiency without a temporary indwelling shunt is presented. The series is
      clinically analysed regarding the incidence of postoperative neurological
      deficits and mortality and statistically analysed concerning factors that may be
      reliable in identifying patients at risk. A transient neurological deficit
      occurred in five patients (1.5%) and a permanent deficit in six (1.7%). The
      mortality rate was 1.5% (five patients). The combined postoperative stroke and
      mortality rate was 2.6%. There was no statistical difference in the incidence of
      neurological deficits relative to operative indication (symptom-free 2.7%;
      transient ischaemic attack 1.4%; prior stroke 2.4%), and to the condition of the
      contralateral internal carotid artery (normal 1.4%; stenosis 2.9%; total
      occlusion 0%); nor between patients with internal carotid artery back pressure
      measurements > 50 mmHg (1.2%), 25-50 mmHg (2.0%) and < 25 mmHg (3.8%). In
      conclusion, carotid endarterectomy without a shunt is a safe procedure with a low
      combined perioperative stroke and mortality rate.

PMID- 7820513
TI  - Evolution of carotid restenosis after endarterectomy.
AB  - Some 176 consecutive carotid endarterectomies performed during 1987 were assessed
      after 11.5 and 44 months. There were four perioperative deaths. At mean follow-up
      of 32.5 months the 50% restenosis rate progressed from 9.7% to 11.9%. Of the 168
      carotid arteries with a normal patency at discharge, 36 showed progression of
      stenoses as judged by duplex scanning during the observation period of 44 months.
      Twenty-nine stenoses were present within 1 year and seven developed between 12
      and 44 months. Successive assessments revealed marked differences in the
      evolution of restenoses which usually depended on the degree of severity reached
      at the end of the first year: 44% progressed, 28% regressed and only 28% remained
      stable. The risk of late occlusion in vessels with a < 50% restenosis at 1 year
      was below 1% and the risk of progressing to a stenosis > 50% was 3.3%. Assessment
      at 56 months was limited to patients who had a restenotic lesion during the first
      44 months. It confirmed that the disease was still unstable with progression in
      7% of cases and regression in 10%. This study did not demonstrate any significant
      restenosis after 20 endarterectomies using the eversion technique compared with
      an incidence of 13.4% after 156 standard endarterectomies.

PMID- 7820514
TI  - Carotid endarterectomy for non-hemispheric ischaemia: long-term follow-up.
AB  - Earlier results reported by the authors suggest that carotid endarterectomy can
      relieve symptoms of non-hemispheric ischemia in patients who present with
      hemodynamically significant carotid stenosis. Long-term follow-up of a subgroup
      of these patients is described. Some 61 patients with non-hemispheric ischemia
      who underwent carotid endarterectomy were reviewed. Indications for surgery and
      postoperative results (stroke, death, symptom relief) were determined by office
      visit or phone interview. Results in these patients were compared with those of
      an entire patient population who underwent endarterectomy performed by the
      authors. Mean (s.d.) follow-up was available for 42.3 (31.7) months.
      Perioperative stroke rate (4.9%), survival (85.3 and 64.9% at 3 and 5 years
      respectively) and stroke-free survival (77.1 and 63.4% at 3 and 5 years
      respectively) were not different from that entire cohort of 553 patients. During
      follow-up, 11 patients (18%) developed recurrent symptoms of non-hemispheric
      ischemia. Carotid endarterectomy is successful in providing long-term relief of
      symptoms of non-hemispheric ischemia in most patients with significant carotid
      bifurcation stenosis. Results in such patients are similar to those seen in
      patients with symptoms of anterior cerebral ischemia or with symptom-free
      stenoses.

PMID- 7820515
TI  - Surgical management of extracranial internal carotid artery aneurysms.
AB  - Between 1980 and 1991, 13 of 1312 carotid artery reconstructions were performed
      for aneurysms of the extracranial internal carotid artery. The patients included
      12 men and one woman, mean age 56 years. Postoperative aneurysms and aneurysms
      involving the common carotid artery were excluded from the study. In six cases,
      the upper part of the aneurysm was higher than a line joining the mandibular to
      the tip of the mastoid process. Six aneurysms were atherosclerotic, two post
      traumatic, four dysplasic and one post-traumatic and atherosclerotic. Nine
      patients had focal neurological symptoms (seven hemispherical, two ocular), one
      presented with cranial nerve compression, two had non-hemispherical symptoms and
      one was symptom-free. Surgical reconstruction was achieved by 12 venous grafts
      and one aneurysmorrhaphy. A conventional cervical approach was used in seven
      cases; in four cases subluxation of the mandible with resection of the posterior
      belly of the digastric muscle and division of the styloid process and its
      attached muscles was used. An infratemporal approach with release of the 7th
      nerve and opening up of the first portion of the carotid canal was used in two
      patients. There were no deaths or strokes but two patients had a transient
      ischaemic attack. In four cases, a cranial nerve palsy developed; one involving
      the 9th nerve did not recover. Patency was assessed by postoperative angiography
      in all cases. Mean (range) follow-up was 46 (4-126) months. One patient died
      after 2 years as a result of myocardial infarction. One patient had a transient
      ischaemic attack during the 2nd postoperative year. All survivors were assessed
      in January 1992, when all reconstructed arteries were patent.

PMID- 7820516
TI  - Division-endarterectomy-anastomosis of the internal carotid artery: a prospective
      randomized comparative study.
AB  - Saphenous vein patch angioplasty is reported to yield superior results for
      carotid endarterectomy. In order to evaluate an alternative technique, which
      leaves the saphenous vein intact for other possible graft purposes, 200 carotid
      endarterectomies were included in a prospective randomized comparative study.
      Patients were randomized to two statistically equivalent groups: one group
      underwent classical carotid endarterectomy through a longitudinal incision with
      saphenous vein patch angioplasty; the other had endarterectomy through an oblique
      division of the internal carotid followed by in situ anastomosis. Cross-clamping
      time was approximately 5min shorter with the division-endarterectomy-anastomosis
      technique. The overall perioperative (< 30 days) mortality rate was 2.5% and
      cumulative mortality-morbidity rate 8% in the patch group compared with 4% in the
      other (P > 0.05). There were significantly more cranial nerve injuries in the
      patch group, most of which were transient (P < 0.01). The mean follow-up was 365
      days. The late mortality rate was 5.5%. There were no late permanent or fatal
      strokes, but 3% of patients sustained mild transient neurological events. Only
      three significant (> 60%) stenoses developed during follow-up, all within 9
      months. Dilatation and disturbed flow were more pronounced in the patch group (P
      < 0.05). There were no statistically significant differences between both
      techniques on mortality, disabling neurological morbidity and recurrent stenosis.
      In conclusion, the results of the division-endarterectomy-anastomosis technique
      are equivalent to those with patch angioplasty, leaving the patient's venous
      capital intact.

PMID- 7820517
TI  - Carotid endarterectomy for symptom-free stenosis: the patient's point of view.
AB  - Determining the indication for carotid endarterectomy in a given patient with a
      totally symptom-free internal carotid artery stenosis depends on objectively
      assessing the risk of non-operative versus operative treatment, as well as on the
      patient's attitude towards immediate versus long-term risk. In order to study
      patients' attitudes and preferences, four groups of subjects were asked to
      complete two questionnaires: the first examined people's perceived deterioration
      in their quality of life if they sustained a stroke of a defined severity. The
      second checked the attitude towards risk of operative versus non-operative
      treatment at different levels of an expected annual stroke rate without surgery.
      This preliminary study showed the feasibility of studying these subjective
      elements, and also pointed to problem areas in this type of research. The
      existence of individual as well as group differences in patients' values and
      preferences should be considered in the decision-making process.

PMID- 7820518
TI  - Carotid artery surgery and the principle of prophylaxis: recurrence in operated
      and nonoperated patients.
AB  - A total of 700 carotid endarterectomies have been performed over a 24-year period
      at the authors' institute; of these patients 632 (90.3%) had unilateral and 68
      (9.7%) had bilateral disease. Some 71 patients who declined operation were
      followed-up to obtain the natural history of carotid disease. The operative
      results were compared against this untreated group of patients. Surgical
      endarterectomy was recommended for a recovered stroke in 190 patients (27.1%),
      progressive ischaemia in 20 (2.9%) and transient ischaemic attacks in 410
      (58.6%). A group of 100 patients with non-specific symptomatology, who were
      considered 'symptom-free', were also operated on; none of these died or developed
      permanent postoperative neurological defects. The mean age of patients was 56
      (range 28-86) years. The overall operative mortality rate was 0.8%. Perioperative
      neurological deficits occurred in 0.5% and temporary cranial nerve injury in
      1.8%. The follow-up covered a period of 10 years, but was in several instances
      extended to 14 years. The incidence of late neurological events in the patients
      having an endarterectomy was 3%. In the non-operated group, 12% of normotensive
      and 18% of hypertensive patients developed symptoms. The 10-year postoperative
      survival rate was 80% in the symptom-free group of patients, 70% in those with
      transient ischaemic attacks and 60% in those who had a previous stroke.

PMID- 7820520
TI  - Surgical reconstruction of the superior vena cava.
AB  - Ten patients (eight men, two women) who underwent surgical reconstruction of the
      superior vena cava using an expanded polytretrafluoroethylene (ePTFE) prosthesis
      between 1981 and 1991 were reviewed to assess the therapeutic value of such
      surgery. The mean (s.d.) age was 55(12) years. Obstruction of the superior vena
      cava was caused by pulmonary or mediastinal cancer in nine patients and chronic
      mediastinitis in one. Eight patients had superior vena cava syndrome and two had
      symptoms of lung disease. The diagnosis of superior vena cava obstruction was
      made before surgery by computed tomography or superior venacavography in eight
      patients and during the surgical procedure in two. Tumour resection was performed
      in five patients. Venous reconstruction was achieved by interposition of an ePTFE
      graft between the proximal and distal end of the vena cava in three patients and
      between one (four cases) or two (three cases) tributaries of the superior vena
      cava and the right atrium in seven. No patient died during the perioperative
      period. Symptoms of superior vena cava obstruction disappeared promptly after
      operation in all patients. Postoperative patency was assessed by cavography or
      computed tomography; all the grafts were patent. During follow-up no patients
      presented with recurrent superior vena cava syndrome. Eight patients died. The
      cumulative survival rates were 70, 25 and 12.5% at 1, 2 and 5 years,
      respectively. Surgical reconstruction of the superior vena cava with an ePTFE
      prosthesis provided immediate and long-term relief of symptoms of superior vena
      cava obstruction with a low surgical morbidity, even in patients with
      unresectable malignancy.

PMID- 7820519
TI  - Morphological, immunohistological and fibrinolytic features of patch grafts for
      reconstruction of the inferior vena cava.
AB  - Morphological and immunohistological features and fibrinolytic activity of the
      neointima of various grafts implanted in the thoracic inferior vena cava (IVC) in
      dogs were examined. Autologous pericardium (group 1), treated porcine pericardium
      (group 2), treated bovine pericardium (group 3), treated horse pericardium (group
      4) and expanded polytetrafluorethylene (e-PTFE) (group 5) were used as patch
      grafts. Grafts harvested 12-30 (mean 15.2) months after implantation were all
      patent in each group. The luminal surface of the grafts was completely covered
      with endothelial cells, which were positive for immunohistological staining of
      factor VIII and had active fibrinolytic activity. The gross appearance of the
      neointima of the grafts in group 1 was smooth; however, the grafts in groups 2-5
      were severely deformed with retraction. The concavity of the retracted grafts in
      groups 2-5 was filled with thick neointima, which consisted of a superficial
      layer with mature smooth muscle cells and the deeper layer with fibroblast-like
      cells and extracellular collagen fibres. Fibroblast-like cells were thought to be
      a synthetic form of fibroblasts. The deeper layer of the neointima of the
      implanted biografts and e-PTFE graft was considered to be in the active phase in
      cell proliferation, even at > or = 12 months after implantation. It is concluded
      that autologous pericardium is the material of choice for patch grafts in
      reconstruction of the IVC and that biografts and synthetic grafts are less than
      satisfactory.

PMID- 7820521
TI  - Should superior vena caval syndrome be treated by surgery any more?

PMID- 7820522
TI  - Pseudoaneurysm of the external carotid artery following radical neck dissection
      and irradiation: a case report and review of the literature.
AB  - A 54-year-old man developed a pseudoaneurysm of the left external carotid artery
      8 years after concluding treatment for squamous cell carcinoma of the tongue.
      Treatment included radiation therapy, radical neck dissection and a myocutaneous
      pectoralis major flap. Percutaneous transcatheter embolization resulted in
      thrombosis of the pseudoaneurysm. A review of the literature yielded only six
      other reported cases of pseudoaneurysm of the external carotid artery proper.

PMID- 7820523
TI  - Subclavian artery aneurysm: the role of magnetic resonance imaging.
AB  - Subclavian artery aneurysms are rare. Diagnosis is important as complications can
      be life threatening. A case is reported which is diagnosed by magnetic resonance
      imaging; moreover it is suggested that magnetic resonance imaging is now the
      initial imaging modality of choice in the investigation of these lesions.

PMID- 7820524
TI  - Fibromuscular dysplasia as a cause of abdominal aortic aneurysm.
AB  - A 53-year-old woman presented with abdominal discomfort and was diagnosed using
      ultrasonography to have an abdominal aortic aneurysm. Aortography revealed a
      saccular aneurysm 4 cm in diameter of the infrarenal aorta with a 'string of
      beads' appearance. The renal and other visceral arteries appeared to be normal.
      Resection and graft replacement was performed because of the possibility of
      rupture. Histological examination of the specimen revealed the most common type
      of fibromuscular dysplasia, namely medial fibroplasia. Fibromuscular dysplasia
      should be considered as a potential cause of abdominal aortic aneurysm in female
      patients with no atherosclerosis risk factors.

PMID- 7820525
TI  - Left-side inferior vena cava and inflammatory abdominal aortic aneurysms: a case
      report.
AB  - The incidence of isolated left-side inferior vena cava ranges from 0.2-0.5%. This
      anomaly is associated infrequently with an abdominal aortic aneurysm. A case is
      reported of left-side inferior vena cava associated with a symptomatic, 5-cm
      inflammatory abdominal aortic aneurysm. Preoperative computed tomography showed a
      perianeurysmal mantle strongly adherent to a left-side inferior vena cava. This
      report is the first of an infrarenal inferior vena cava anomaly associated with
      an inflammatory abdominal aortic aneurysm. The technical details required to
      perform the aortic reconstruction via a transperitoneal approach are described
      and discussed.

PMID- 7820526
TI  - Reoperative myocardial revascularization: an analysis of 458 reoperations and
      2645 single operations.
AB  - A consecutive series of 2645 patients underwent primary coronary bypass grafting
      while 458 patients underwent reoperative bypass during a 9-year period. The mean
      age (61 years), sex distribution (83% men) and preoperative risk factors were
      identical in the two groups. Significantly more patients belonged to New York
      Heart Association (NYHA) class 4 and were clinically unstable in the reoperative
      group (P < 0.001). The internal mammary artery was used in 43% of the single
      operation group but in only 23% of patients who subsequently required reoperation
      (P < 0.001). In reoperations 61% of the patients had an internal mammary artery
      graft (P < 0.001). The overall operative mortality rate for single operation was
      2.3% (62/2645) versus 9.2% (42/458) for reoperations. Patients with a reoperative
      interval of more than 1 year had a 8.4% mortality rate, compared with 28% in
      those reoperated on 1 year or less after the initial operation (P < 0.01).
      Preoperative myocardial infarction, intra-aortic balloon pump insertion,
      prolonged ventilatory support and ventricular arrhythmias were all prevalent
      after reoperations (all P > 0.001), while postoperative myocardial infarctions
      and re-sternotomy for bleeding did not differ between the groups. Emergency
      operation, preoperative NYHA class 3-4 and poor left ventricular function were
      predictors of perioperative mortality in both groups. Left main stem stenosis was
      an added factor in the reoperative group. After reoperation 93% of the hospital
      survivors were alive at 5 years after surgery; the cardiac event-free rate was
      59% and > 90% of the patients showed improvement of their NYHA class during the
      follow-up. Reoperative coronary artery bypass grafting is effective, but has an
      increased operative mortality and morbidity, especially in patients with unstable
      angina, left main stem stenosis and poor preoperative left ventricular function.

PMID- 7820527
TI  - Assisted circulation in postcardiotomy heart failure: experience with the Bio
      Medicus centrifugal pump in ten patients.
AB  - Between January 1990 and September 1992, ten patients required assisted
      circulation for postcardiotomy heart failure which was unresponsive to inotropic
      drugs and aortic counterpulsation. All patients were supported by a Bio-Medicus
      centrifugal pump (biventricular assist in five, left ventricular in three, right
      ventricular in two); six had ischaemic heart disease, two a congenital
      ventricular septal defect, one an acute mitral valve incompetence and one an
      aortic type 'A' dissection. The mean duration of circulatory support was 5.1 days
      (range 2 hours to 8 days). Six patients were weaned from the device and four were
      discharged; the perioperative deaths among the patients weaned from support were
      the result of cerebral haemorrhage and multiorgan failure respectively. No late
      deaths occurred at a mean follow-up of 15 months. Common complications were
      bleeding (40%), acute renal failure (30%) and sepsis (30%). All patients who
      developed renal failure died. The high incidence of haemorrhagic complications
      makes the use of pre-heparinized circuits desirable as these patients do not then
      require additional anticoagulation.

PMID- 7820528
TI  - Reduction of myocardial necrosis by positioning the intra-aortic balloon pump in
      the ascending aorta.
AB  - The presence of severe peripheral vascular disease may necessitate inserting an
      intra-aortic balloon pump (IABP) directly into the ascending aorta. As
      positioning an IABP into the descending aorta may be hazardous and difficult
      through the ascending aorta, this experimental study sought to determine the
      effects of positioning an IABP in the ascending aorta on myocardial recovery
      during urgent surgical revascularization. The second and third diagonal coronary
      arteries in 30 pigs were occluded with snares for 90 min followed by 30 min of
      cardioplegic arrest and 180 min of reperfusion with the snares released. During
      the period of coronary occlusion, ten pigs received an IABP in the descending
      aorta, ten had an ascending aorta IABP and ten received no IABP support. The best
      recovery of wall motion, least tissue acidosis and lowest area of necrosis
      occurred when an IABP was positioned in the ascending aorta. It is concluded that
      myocardial recovery is enhanced when an IABP is positioned in the ascending aorta
      during urgent surgical revascularization.

PMID- 7820529
TI  - Embolizing fibroelastoma of the aortic valve.
AB  - Papillary fibroelastomas are very rare cardiac tumours that can present with
      embolization of coronary and peripheral arteries and sudden death. The diagnosis
      can be made by two-dimensional or transoesophageal echocardiography. A 53-year
      old man with an aortic valve papillary fibroelastoma who presented with several
      transient ischaemic attacks is reported.

PMID- 7820530
TI  - Intravenous leiomyomatosis extending into the right atrium.
AB  - Intravenous leiomyomatosis, also called benign leiomyoma, is a rare tumour that
      originates from a uterine myoma and spreads intravenously. A 54-year-old woman
      who had experienced faintness after a hysterectomy for uterine myoma 10 years
      earlier presented with this lesion. Ultrasonographic, computed tomographic and
      angiographic examination revealed a long tumour that originated in the uterus and
      extended into the right atrium through the right internal iliac vein and inferior
      vena cava. On the basis of a diagnosis of intravenous leiomyomatosis the neoplasm
      was extirpated by a one-stage cardiotomy and laparotomy with the aid of
      cardiopulmonary bypass. Retrospective histological analysis of the excised uterus
      revealed tumorous thrombosis in the venous cavity of the tunica muscularis. Some
      26 cases in which open-heart surgery has been undertaken for intracardiac tumour
      thrombosis have been reported. These and the case described here are reviewed and
      analysed. In the present case, a full view of the tumour was obtained before
      surgery, and the lesion removed by a one-stage procedure using median sternotomy
      (cardiotomy) and laparotomy. Reports of one-stage procedures are few; only eight
      (30%) of 27 cases.

PMID- 7820531
TI  - Addisonian crisis following pericardiectomy.
AB  - In developing countries tuberculosis is a common cause of constrictive
      pericarditis and its involvement of other organs may sometimes complicate the
      surgical management of such patients. A case is reported of constrictive
      pericarditis in which the patient developed protracted hypotension which was
      unresponsive to inotropic therapy, following pericardiectomy. On investigation
      the cause of hypotension was diagnosed as acute adrenocortical insufficiency,
      secondary to adrenal tuberculosis. The patient was successfully treated with
      corticosteroids. Low cardiac output after pericardiectomy, which is not uncommon,
      should not necessarily be attributed to a 'myocardial factor'. Patients with
      tuberculous pericarditis may have co-existent Addison's disease.

PMID- 7820532
TI  - Ectopic expression of NCAM in mouse fibroblasts stimulates self-aggregation, and
      promotes integration into primary cerebellum cell aggregates.
AB  - We have undertaken aggregation experiments using mouse LMTK(-)-fibroblasts
      transfected with various isotypes of the neural cell adhesion molecule, NCAM. We
      found that self-aggregation of NCAM-positive fibroblasts is enhanced compared to
      control-transfected cells. The aggregation properties are partly dependent on the
      expressed NCAM isotype. Fibroblasts expressing a NCAM 140 isotype with exons a3
      and pi were further tested in primary cerebellum cell re-aggregation experiments.
      While control-transfected fibroblasts could not be found in forming aggregates,
      fibroblasts ectopically expressing NCAM were integrated into neural cell
      aggregates. Time-lapse photography indicated that the nascent primary cell
      aggregates actively participated in the integration process by migration and
      attachment to nearby NCAM-positive fibroblasts.

PMID- 7820533
TI  - Further studies on the interaction of migrating keratinocytes with fibrinogen.
AB  - If glass implants placed under one edge of a skin wound in the adult newt are
      coated with fibrinogen (FGN), keratinocytes from the wound periphery migrate onto
      the implant. To learn more about the site(s) in FGN that permits this migration,
      we exposed keratinocytes to implants coated with forms of FGN containing
      modifications or deletions in the 3 most commonly studied cell binding sites; the
      RGDF sequence at A alpha 95-98, RGDS at A alpha 572-575 and the carboxy terminal
      12 amino acids in the gamma A chain. Recombinant FGN with either RGD sequence
      altered to RGE supported migration as well as unmodified FGN did. Replacement of
      the carboxy terminal 4 amino acids in the gamma A chain by a 20 amino acid
      sequence that disrupts the ability of the gamma terminus to mediate platelet
      aggregation (the gamma' variant) likewise had no effect. Nor did simultaneous
      antibody blockade of the RGDS, RGDF, and gamma A sites have any effect. At its
      best, Dhem1, a fragment containing the RGDS and gamma A sites, produced only
      about half as much migration as the maximum obtained on intact FGN. Dhem2, a
      fragment differing from Dhem1 only by having a gamma' variant in place of gamma
      A, was even less active. Two other D fragments, both of which were missing a
      large part of the A alpha chain, and one of which contained none of the three
      major binding sites, supported considerable migration, suggesting that loss of
      the A alpha chain COOH terminus reveals a site that was not exposed in Dhem1 and
      2. A alpha chain fragments containing the RGDF or RGDS sequence were active, but
      a much larger fragment without RGD was inactive. A soluble peptide consisting of
      the sequence, RGDS, was a potent inhibitor of migration on FGN but RGDF and the
      gamma A pentapeptide, KQAGD, were minimally effective. Longer versions of these
      peptides decreased the effectiveness in all cases. These results suggest that
      under certain circumstances, newt keratinocytes may interact with each of the 3
      major binding sites in FGN as well as a site outside these sequences.

PMID- 7820534
TI  - Adhesion of human epidermal keratinocytes to laminin.
AB  - We have examined the mechanism by which human epidermal keratinocytes adhere to
      the A/B1/B2 (alpha 1 beta 1 gamma 1) form of laminin. Adhesion could be
      completely inhibited with an antibody to the beta 1 integrin subunit or a
      combination of antibodies recognising the alpha 2 beta 1, alpha 3 beta 1 and
      alpha 6 beta 4 integrins. Keratinocytes adhered in the presence of magnesium and
      manganese ions, but calcium ions did not support adhesion and inhibited adhesion
      when combined with magnesium and manganese. The effects of anti-integrin
      antibodies (including a stimulatory antibody to the beta 1 subunit) were not
      influenced by specific cations, with the exception that inhibition by an antibody
      to alpha 2 beta 1 was abrogated by the presence of manganese ions. The E3 and E8
      proteolytic fragments of laminin did not support keratinocyte adhesion and heat
      inactivation of the E8 site in intact laminin did not reduce adhesion. Three
      laminin fragments that did support adhesion were P1, E4 and E1X-Nd, P1 activity
      being attributable at least in part to the RGD site; antibody blocking
      experiments suggested that adhesion to these fragments was primarily via alpha 3
      beta 1. The synthetic peptide GD-6, derived from the carboxy terminus of the
      laminin A chain (included within E3) did support adhesion, but the significance
      of this observation is unclear, since a scrambled control peptide could also
      support adhesion. In conclusion, keratinocyte adhesion to A/B1/B2 laminin
      involves three integrins and multiple binding sites that are different from those
      defined previously.

PMID- 7820535
TI  - A short core region of E-cadherin is essential for catenin binding and is highly
      phosphorylated.
AB  - Classical cadherins associate with three cytoplasmic proteins, termed alpha, 
      beta- and gamma-catenin. This association mediates the attachment of cadherins to
      the microfilament network, which is believed to be of major importance for
      cadherin function. Deletion of the carboxyterminal 72-amino acid residues of E
      cadherin had been previously shown to prevent catenin binding. Here we have
      analyzed additional mutants of E-cadherin with deletions within this region and
      identified a core region of 30 amino acids (E-cadherin pos. 832-862) essential
      for the interaction with catenins. Phosphorylation analysis of wild-type and
      mutant E-cadherin indicates that the catenin-binding domain is highly
      phosphorylated. In particular, the 30 amino acid region contains 8 serine
      residues which are well conserved among cadherins. To elucidate whether
      phosphorylation might be important for cadherin-catenin complex formation, site
      directed mutagenesis experiments were performed. Partial substitutions of up to 5
      of the 8 serine residues in the cluster had no influence on E-cadherin-catenin
      complex formation and E-cadherin mediated cell adhesion, although phosphorylation
      of E-cadherin was reduced. In contrast, substitution of the whole serine cluster
      completely abolished phosphorylation and affected complex formation with
      catenins. These results suggest that E-cadherin-catenin interaction may be
      regulated by phosphorylation of the catenin-binding domain, which might represent
      one molecular mechanism to regulate cadherin mediated cell adhesion.

PMID- 7820536
TI  - Is intercellular communication via gap junctions required for myoblast fusion?
AB  - Fusion of myoblasts to form syncitial muscle cells results from a complex series
      of sequential events including cell alignment, cell adhesion and cell
      communication. The aim of the present investigation was to assess whether
      intercellular communication through gap junctions would be required for
      subsequent membrane fusion. The presence of the gap junction protein connexin 43
      at areas of contact between prefusing rat L6 myoblasts was established by
      immunofluorescent staining. These myoblasts were dye-coupled, as demonstrated by
      the use of the scrape-loading/dye transfer technique. L6 myoblast dye coupling
      was reversibly blocked by heptanol in short term experiments as well as after
      chronic treatment. After a single addition of 3.5 mM heptanol, gap junctions
      remained blocked for up to 8 hours, then this inhibitory effect decreased
      gradually, likely because the alcohol was evaporated. Changing heptanol solutions
      every 8 hours during the time course of L6 differentiation resulted in a lasting
      drastic inhibition of myoblast fusion. We further investigated the effect of
      heptanol and of other uncoupling agents on the differentiation of primary
      cultures of embryonic chicken myoblasts. These cells are transiently coupled by
      gap junctions before myoblast fusion and prolonged application of heptanol,
      octanol and 18-beta-glycyrrhetinic acid also inhibited their fusion. The effect
      of heptanol and octanol was neither due to a cytotoxic effect nor to a
      modification of cell proliferation. Moreover, heptanol treatment did not alter
      myoblast alignment and adhesion. Taken together these observations suggest that
      intercellular communication might be a necessary step for myoblast fusion.

PMID- 7820537
TI  - The role of infection in inflammatory arthritis.

PMID- 7820538
TI  - Molecular pathology of alpha 1-antitrypsin deficiency and its significance to
      clinical medicine.
AB  - alpha 1-Antitrypsin (AAT) deficiency is associated with predisposition to
      developing liver cirrhosis in early childhood, and chronic degenerative lung
      disease in early adult life. The probable molecular basis for the disease
      associations is known. One of the common variants, Z, has the propensity to form
      polymers, a phenomenon which is concentration- and temperature-dependent. This
      results in accumulation of the protein in hepatocytes, the predominant tissue
      source of AAT, and leads to cell damage. AAT deficiency results in loss of
      protection in the lung against neutrophil elastase (NE) the major target for AAT.
      NE is capable of destroying the architecture of the lung, leading to pulmonary
      emphysema. The disease process is exacerbated by cigarette smoke, which is
      capable of oxidizing a critical methionine residue at the active site, rendering
      AAT an inefficient inhibitor of NE. The combination of deficiency and cigarette
      smoking are critical to the development of pulmonary emphysema. We have
      identified a mutation in an enhancer sequence which, in all probability,
      predisposes to disease by a novel mechanism related to diminished expression of
      AAT during inflammation. Our understanding of the mechanisms of disease should
      lead to improved therapeutic interventions.

PMID- 7820539
TI  - The relationship between blood pressure and left ventricular mass in essential
      hypertension is observed only in the presence of the angiotensin-converting
      enzyme gene deletion allele.
AB  - An insertion/deletion polymorphism in the angiotensin-converting enzyme (ACE)
      gene accounts for approximately 50% of the variance in plasma ACE concentration:
      deletion homozygotes (DD) have the highest, and insertion homozygotes (II) the
      lowest ACE concentrations. ACE is responsible for the generation of angiotensin
      II, which is implicated in the development of left ventricular hypertrophy, an
      independent risk factor for morbidity and mortality in hypertension. The aim of
      this study was to investigate the contribution of ACE genotype to the development
      of left ventricular hypertrophy in patients with essential hypertension. Eighty
      five patients with essential hypertension underwent echocardiographic assessment
      of left ventricular mass index (LVMI) and determination of ACE genotype from
      leukocyte DNA by polymerase chain reaction. There was no significant difference
      in LVMI among the genotypes (II, ID, DD). Analysis of covariance modelled for
      LVMI showed a significant interaction with systolic blood pressure (p = 0.036)
      but not diastolic blood pressure (p = 0.453). The relationship between LVMI and
      systolic blood pressure was strongest in the deletion homozygotes (p = 0.002, R2
      = 0.47), and also present in the heterozygotes (p = 0.013, R2 = 0.40). No
      relationship was seen in the insertion homozygotes (p = 0.914, R2 = 0.23). These
      findings suggest that the effect of blood pressure on LVMI in essential
      hypertension is expressed only in the presence of the ACE gene deletion allele.

PMID- 7820540
TI  - Hereditary caeruloplasmin deficiency, dementia and diabetes mellitus.
AB  - We report two brothers with complete caeruloplasmin deficiency. The brothers
      presented with dementia and diabetes mellitus. Twelve relatives have partial
      caeruloplasmin deficiency. There is no copper overload. Transmission is autosomal
      recessive. DNA analysis showed genetic linkage between the deficiency and various
      polymorphic markers flanking the caeruloplasmin gene on chromosome 3q25. This is
      consistent with a mutation of the caeruloplasmin gene. Caeruloplasmin catalyses
      the oxidation of ferrous iron to ferric iron. Both brothers have low serum iron
      and increased liver iron. The index patient was given caeruloplasmin-containing,
      fresh-frozen plasma. A dose of 2.6 mg caeruloplasmin increased serum iron from 5
      microM/l to 10 microM/l. A dose of approximately 72 mg increased serum iron from
      5 microM/l to 19 microM/l. The abnormal serum and liver iron levels, and the
      caeruloplasmin-induced rise in serum iron, confirm a previous suggestion that
      caeruloplasmin maintains the normal rate of flow of iron from store to
      transferrin. Dementia and diabetes mellitus have been described in only one other
      homozygote. The absence of copper overload, and the linkage of the deficiency
      with chromosome 3q25, distinguish this condition from Wilson's disease.

PMID- 7820541
TI  - Birmingham Vasculitis Activity Score (BVAS) in systemic necrotizing vasculitis.
AB  - The continuing morbidity of patients with vasculitis, despite the improved
      prognosis with aggressive therapy, underlines the need for accurate disease
      assessment. We have devised a clinical index of disease activity, and evaluated
      its use in several forms of necrotizing vasculitis. The weighted score is based
      on symptoms and signs in nine separate organ systems. Disease features are only
      scored if they are attributable to active vasculitis. The Birmingham Vasculitis
      Activity Score (BVAS) was compared with two other published vasculitis activity
      scores, with the physician's global assessment (PGA), with outcome, and with
      serological markers of disease activity. In a cross-sectional study of 213
      consecutive patients with different forms of vasculitis, all 107 vasculitis
      patients who were judged completely well on clinical assessment had a BVAS score
      of 0. Twenty-two patients with active vasculitis prior to treatment had a median
      score of 7.5 (range 4-30) and 69 with active disease on treatment had a median
      score of 10 (1-29). Of the 12 who died, median score immediately prior to death
      was 20.5 (9-30). In a serial prospective study, 30 cases had documented episodes
      of active disease. During periods of disease activity, the median BVAS values
      were significantly higher than in remission (15 [range 3-32] vs. 0 [0-2], p <
      0.001); the same was true for CRP values (80 [9-361] vs. 13.5 [5-68], p < 0.001).
      This was not true for erythrocyte sedimentation rate (ESR), haemoglobin (Hb) or
      von Willebrand factor (VWF).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7820542
TI  - Oxidative stress in haemodialysis.
AB  - Patients with chronic renal failure, including those receiving regular long-term
      haemodialysis, have a high incidence of premature cardiovascular disease.
      Oxidative stress, which occurs when there is excessive free-radical production or
      low antioxidant levels, has recently been implicated as a causative factor in
      atherogenesis. The aim of this study was to determine if chronic renal failure
      and haemodialysis were associated with increased oxidative stress. Serum
      malondialdehyde was measured as a marker of lipid peroxidation in 15 patients
      with conservatively managed chronic renal failure (CRF), 15 patients with CRF
      undergoing regular haemodialysis and 15 healthy controls. Selenium, glutathione
      peroxidase and antioxidant vitamins were also measured. Malondialdehyde was
      elevated in dialysis patients in comparison to CRF and control groups (dialysis
      1.16 +/- 0.08 mumol/l, CRF 0.94 +/- 0.07, controls 0.66 +/- 0.10). Antioxidants,
      including vitamin C, selenium and glutathione peroxidase, were decreased in
      dialysis patients and to a lesser extent in the CRF group (vitamin C-dialysis
      16.43 +/- 3.76 mumol/l, CRF 34.5 +/- 8.6, controls 56.11 +/- 7.41; selenium
      dialysis 0.77 +/- 0.07 mumol/l, CRF 0.69 +/- 0.06, controls 1.09 +/- 0.06:
      glutathione peroxidase-dialysis 101 +/- 5 U/l, CRF 160 +/- 11, controls 290 +/-
      10). These findings indicate oxidative stress in patients with CRF which is
      further exacerbated by haemodialysis, as evidenced by increased lipid
      peroxidation and low antioxidant levels. This stress may play a role in the
      development of atherosclerosis in these groups.

PMID- 7820543
TI  - Long-term follow-up after total parathyroidectomy without parathyroid
      reimplantation in chronic renal failure.
AB  - Forty-three patients with secondary or autonomous hyperparathyroidism
      complicating chronic renal failure (CRF) underwent total parathyroidectomy (PTX)
      (follow-up 2-18 years, mean 8.7 years). Five were on conservative treatment for
      CRF, 35 on regular dialysis, and only three had a functioning allograft. At PTX,
      the most frequent findings were uncontrollable hypercalcaemia, musculo-skeletal
      pain, radiographic changes in the phalanges, and raised plasma parathyroid
      hormone (PTH) concentration. Pre-operatively, all patients were loaded with
      dihydrotachysterol or 1-alpha-OH cholecalciferol. Postoperatively, they were
      maintained on tapering doses of the same drugs and, briefly, oral calcium
      supplements. Five glands were identified and removed in two patients, four in 35
      patients, three in three patients and only two in one patient. All had changes of
      hyperplasia and adenoma formation, except for one with a parathyroid carcinoma.
      Prompt symptomatic and radiographic improvement occurred, with normalization of
      plasma calcium and alkaline phosphatase. Postoperative PTH levels were available
      in 33 patients (23 by intact PTH assay): they were persistently high in 10/33
      (2/23 intact); normal in seven (6 intact); low in 11 (3 intact), and undetectable
      in four (3 intact). Thus, PTX was incomplete in the majority of patients.
      Following transplantation, 3/20 (3/18 intact) patients still had detectable PTH.
      Only one patient developed symptomatic recurrent parathyroid disease requiring re
      operation, and complications were few. Small dosages of vitamin D continue to be
      required, but not calcium supplementation, and no clinical effects of possible
      adynamic bone have been noted. At later renal transplantation in 27 patients, an
      easily treatable, uncomplicated hypocalcaemia was noted in 33%.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7820544
TI  - Motor neurone disease--a study of prevalence and disability.
AB  - We conducted a point prevalence study of motor neurone disease in the counties of
      South Glamorgan, Mid Glamorgan and Gwent, whose combined population is estimated
      at 1,394,400. A total of 56 patients were identified, giving a point prevalence
      for motor neurone disease in this area of 4.02/100,000 on 22/06/92. These cases
      were reclassified according to the World Federation of Neurology criteria for
      amyotrophic lateral sclerosis following a further clinical assessment, when
      disability was also evaluated (in 49 cases). Seven patients were reclassified on
      review of their medical records alone. Overall, 38 were classified as either
      definite or probable cases, which gave a point prevalence of 2.73/100,000. Of
      these patients, 94% (46/49) were living at home, 43% (21/49) scored 15 or less on
      the Barthel index, 65% (32/49) had some degree of mobility impairment, and 20%
      (10/49) were wheelchair-dependent. Swallowing speed was reduced (< 10 ml/s) in
      67% (33/49), with three requiring feeding through a percutaneous gastrostomy
      tube. Vital capacity was < 70% of predicted value for age, sex and height in 67%
      (29/43). One patient was receiving domiciliary ventilation. These results give a
      quantitative indication of the dependency in a population of patients with motor
      neurone disease.

PMID- 7820545
TI  - Therapeutic trials in primary biliary cirrhosis.

PMID- 7820546
TI  - Proteasome components with reciprocal expression to that of the MHC-encoded LMP
      proteins.
AB  - BACKGROUND: Intracellular proteins are processed into small peptides that bind
      HLA class I molecules of the major histocompatibility complex (MHC) in order to
      be presented to T lymphocytes. The proteasome, a multi-subunit protease, has
      recently been implicated in the generation of these peptides. Two genes encoding
      proteasome subunits, LMP2 and LMP7, are tightly linked to the TAP peptide
      transport loci in the class II region of the human MHC. Inclusion of the LMP
      subunits may alter proteasome activity, biasing it towards the production of
      peptides with carboxyl termini appropriate for binding HLA class I molecules.
      Nevertheless, mutant cells that lack the LMP genes are able to process and
      present antigens at the cell surface at similar levels to wild-type cells. These
      results raise questions about the role of the proteasome, and in particular of
      the LMP subunits, in antigen processing. RESULTS: We have cloned the genes
      encoding a new proteasome subunit, MB1, which is closely related to LMP7, and
      that encoding a second subunit, Delta, which is closely related to LMP2.
      Expression of the MB1 and delta genes is reciprocal to that of the LMP genes: MB1
      and delta are up-regulated in mutant cell lines lacking LMPs and down-regulated
      in the presence of gamma-interferon. The MB1 and delta genes are found to be
      located on chromosomes 14 and 17, respectively, raising interesting evolutionary
      questions about how the LMP genes independently became incorporated into the MHC.
      CONCLUSIONS: We suggest that the subtle phenotype of LMP-deficient cell lines
      results from the compensatory expression in these lines of two other proteasome
      subunits, MB1 and Delta.

PMID- 7820547
TI  - Chromosomal homogeneity of Drosophila ribosomal DNA arrays suggests
      intrachromosomal exchanges drive concerted evolution.
AB  - BACKGROUND: The individual copies of tandemly repeated genes, such as ribosomal
      DNA (rDNA), evolve coordinately within a species. This phenomenon has been called
      concerted evolution, and is thought to be caused by sequence-homogenizing
      mechanisms, such as gene conversion or unequal crossing-over between individual
      copies of the gene family. As these processes would act between the arrays on
      homologous and non-homologous chromosomes, the whole family of repeats would be
      expected to undergo homogenization in a given interbreeding population. RESULTS:
      In order to study the homogenization process, we have examined polymorphisms
      within the internal transcribed spacer (ITS) of the rDNA in populations of
      Drosophila melanogaster at the sequence level, by DNA sequencing and temperature
      gradient gel electrophoresis. Among 84 ITS clones sequenced from five different
      wild-type strains, we found three polymorphic sites that are apparently in the
      process of homogenization. However, these three sites, as well as combinations of
      them, occurred at different frequencies in the different strains. Moreover,
      temperature-gradient gel electrophoresis analysis of an ITS fragment including
      these three sites shows that single chromosomes from locally interbreeding
      populations can harbor rDNA arrays that are largely homogenized for different
      sequence variants. CONCLUSIONS: The presence of chromosomal arrays that are
      homogeneous for different variants in interbreeding populations of Drosophila
      melanogaster indicates that there is little recombination between the chromosomes
      while new mutations are being homogenized along the individual arrays. The most
      likely explanation for this finding is that intrachromosomal recombination events
      occur at much higher rates than recombination between homologous chromosomes.
      Thus, the first step of the homogenization process would occur mainly within
      chromosomal lines. Such behavior of tandem repeat arrays suggests a simple
      explanation of how selection can act on a multigene family, namely by acting on
      whole chromosomally confined repeat arrays rather than on individual repeat
      units.

PMID- 7820548
TI  - Structures of poliovirus complexes with anti-viral drugs: implications for viral
      stability and drug design.
AB  - BACKGROUND: Picornaviruses, such as the structurally related polioviruses and
      rhinoviruses, are important human pathogens which have been the target of major
      drug development efforts. Receptor-mediated uncoating and thermal inactivation of
      poliovirus and rhinovirus are inhibited by agents that bind to each virus by
      inserting into a pocket in the beta barrel of the viral capsid protein, VP1. This
      pocket, which is normally empty in human rhinovirus-14 (HRV14), is occupied by an
      unknown natural ligand in poliovirus. Structural studies of HRV14-drug complexes
      have shown that drug binding causes large, localized changes in the conformation
      of VP1. RESULTS: We report the crystal structures of six complexes between
      poliovirus and capsid-binding, antiviral drugs, including complexes of four
      different drugs with the Sabin vaccine strain of type 3 poliovirus, and complexes
      of one of these drugs with two other poliovirus strains that contain sequence
      differences in the drug-binding site. In each complex, the changes in capsid
      structure associated with drug binding are limited to minor adjustments in the
      conformations of a few side chains lining the binding site. CONCLUSIONS: The
      minor structural changes caused by drug binding suggest a model of drug action in
      which it is the conformational changes prevented by the bound drug, rather than
      obvious conformational changes induced by drug binding, which exert the
      biological effect. Our results, along with additional structures of rhinovirus
      drug complexes, suggest possible improvements in drug design, and provide
      important clues about the nature of the conformational changes that are involved
      in the uncoating process.

PMID- 7820549
TI  - The activation of phosphatidylinositol 3-kinase by Ras.
AB  - BACKGROUND: Activation of the mammalian phosphatidylinositol 3-kinase complex can
      play a critical role in transducing growth factor responses. The lipid kinase
      complex, which is made up of p85 alpha and p110 alpha regulatory and catalytic
      subunits, becomes associated with a number of activated receptor protein tyrosine
      kinases, but the mechanism of its activation has not yet been defined. Recent
      evidence indicates that Ras can bind to the p85 alpha/p110 alpha complex. We
      describe here the functional regulation of the mammalian phosphatidylinositol 3
      kinase complex by Ras. RESULTS: Expression of p110 alpha, the catalytic subunit
      of phosphatidylinositol 3-kinase, in the fission yeast, Schizosaccharomyces
      pombe, has been used to demonstrate an inhibitory effect of p85 alpha on p110
      alpha activity in intact cells; inhibition did not result from a decrease in p110
      alpha expression. In this cellular context, we have investigated the effect of a
      constitutively active mutant of Ras, v-Ras, either on p85 alpha or p110 alpha
      alone, or on the p85 alpha/p110 alpha complex. In the presence of the p85
      alpha/p110 alpha complex, v-Ras suppressed cell growth, but an effector-domain
      mutant of v-Ras did not. The growth-suppressive effect of v-Ras was not seen for
      any other combination of expressed proteins. The phenotype induced by v-Ras was
      consistent with activation of the p85 alpha/p110 alpha complex: it was sensitive
      to the phosphatidylinositol 3-kinase inhibitor, wortmannin, and the cells
      accumulated 3-phosphorylated polyphosphoinositides. Activation of purified p85
      alpha/p110 alpha by purified recombinant Ras in vitro was also demonstrated.
      CONCLUSIONS: The phosphatidylinositol 3-kinase complex, p85 alpha/p110 alpha,
      shows a suppressed catalytic function in vivo when compared with free p110 alpha.
      This complex can, however, be activated by Ras. We suggest that the
      phosphatidylinositol 3-kinase p85 alpha/p110 alpha complex is a downstream
      effector of Ras.

PMID- 7820550
TI  - Neural signalling. Neuromodulatory astrocytes.
AB  - The discovery that waves of increased cytoplasmic free Ca2+ in astrocytes can
      trigger neuronal Ca2+ responses hints at previously unrecognized active
      neuromodulatory roles for glial cells.

PMID- 7820551
TI  - Plant cell expansion. Unzipped by expansins.
AB  - Newly discovered plant proteins, known as expansins, break hydrogen bonds in the
      cell wall and may play an important role in plant growth.

PMID- 7820552
TI  - Neural coding. Neurons cleverer than we thought?
AB  - Neurons may encode information in more subtle ways than their average firing
      rate; encoding by more complex features of a neuron's firing pattern may allow
      more efficient information transmission.

PMID- 7820553
TI  - Neural development. Fate diverted.
AB  - Signals that alter cell fate are probably crucial in metazoan development. Glial
      growth factor may play such a role in the mammalian neural crest, by regulating
      the generation of neurons and Schwann cells.

PMID- 7820554
TI  - Cell cycle. In and out of the cell cycle.
AB  - Studies of fission yeast are shedding light on how the same genes allow cells to
      respond to their environment either by growing and proliferating mitotically or
      by arresting growth to allow differentiation and meiosis.

PMID- 7820555
TI  - Somatosensory development. A new level of refinement.
AB  - Gene 'knockout' mice lacking a critical NMDA-receptor subunit have a brief life
      span, but have already resolved some long-standing controversies about the
      development of the rodent somatosensory system.

PMID- 7820556
TI  - Trefoil peptides. Coming up clover.
AB  - Now that information on trefoil domain structure is available from X-ray
      crystallographic and nuclear magnetic resonance spectroscopy studies, we can
      begin to understand the functions of these unusual protein motifs.

PMID- 7820557
TI  - Speciation. Spinning the web of life.
AB  - Phylogenetic trees based on molecular and morphological data show that diverse
      spider species found on the Hawaiian islands have evolved following multiple
      colonization events.

PMID- 7820558
TI  - Plant phototransduction. Phytochrome signal transduction.
AB  - Signalling intermediates in plant phototransduction pathways have been
      identified. These new results suggest how plants maintain a hight photosyntheic
      efficiency despite changes in their light environment.

PMID- 7820559
TI  - Plant genetics. Pollen clusters.
AB  - New Arabidopsis mutations that result in all four products of meiosis being held
      together as a tetrad of fused pollen grains may facilitate genetic mapping and
      lead to new insights into pollen biology.

PMID- 7820560
TI  - Synaptic plasticity. A molecular switch for memory.
AB  - The metabotropic glutamate receptor controls a molecular switch that, when
      activated, generates a conditioned state essential for the induction of long-term
      potentiation of synaptic transmission in the hippocampus.

PMID- 7820561
TI  - Image manipulation. Confocal images to go?
AB  - Biologists are no longer restricted to using a single algorithm in their
      manipulation and display of data acquired using confocal microscopy.

PMID- 7820562
TI  - Functional cooperativity of human cortical motor areas during self-paced simple
      finger movements. A high-resolution MRI study.
AB  - Magnetic resonance imaging of changes in cerebral blood oxygenation (CBO)
      delineated areas of neural activation during self-paced unilateral middle finger
      tapping in five normal volunteers. Four contiguous imaging sections parallel to
      the bicommissural plane covered the hand area of the primary sensori-motor cortex
      bilaterally. All measurements were performed at 2.0 T using rapid gradient-echo
      sequences (TR/TE = 63/30 ms) with high spatial resolution (0.8 x 1.6 x 4 mm) and
      both strong (40 degrees flip angle) and weak (10 degrees) radiofrequency
      excitation pulses. This allows differentiation of flow and CBO contributions to
      the observed signal alterations. Functional cooperativity was analysed by a pixel
      by-pixel correlation of signal intensity time courses with the stimulus protocol.
      Areas of activation included the contralateral primary motor cortex, the
      homologue part of the primary sensory cortex, the supplementary motor area (SMA)
      and the lateral premotor areas in all volunteers. Task-related activation of
      ipsilateral primary motor cortex above a threshold correlation coefficient of 0.5
      was seen in two out of five volunteers (at 40 degrees) and one out of five (at 10
      degrees) when performing the right-hand task. The present MRI findings readily
      demonstrate in single subjects that the SMA is involved in self-paced finger
      tapping. Only sparse activation in the ipsilateral primary motor cortex is
      consistent with the motor paradigm used.

PMID- 7820563
TI  - The role of the right hemisphere in the interpretation of figurative aspects of
      language. A positron emission tomography activation study.
AB  - We investigated cerebral activity in six normal volunteers using PET to explore
      the hypothesis that the right hemisphere has a specific role in the
      interpretation of figurative aspects of language such as metaphors. We also
      mapped the anatomical structures involved in sentence comprehension. During
      regional cerebral blood flow measurement subjects were asked to perform three
      different linguistic tasks: (i) metaphorical comprehension; (ii) literal
      comprehension of sentences; and (iii) a lexical-decision task. We found that
      comprehension of sentences compared with the lexical-decision task, induced
      extensive activation in several regions of the left hemisphere, including the
      prefrontal and basal frontal cortex, the middle and inferior temporal gyri and
      temporal pole, the parietal cortex and the precuneus. Comprehension of metaphors
      was associated with similar activations in the left hemisphere, but in addition,
      a number of sites were activated in the right hemisphere: the prefrontal cortex,
      the middle temporal gyrus, the precuneus and the posterior cingulate. We conclude
      that the interpretation of language involves widespread distributed systems
      bilaterally with the right hemisphere having a special role in the appreciation
      of metaphors.

PMID- 7820564
TI  - Brain activity during reading. The effects of exposure duration and task.
AB  - Brain activity during reading tasks was investigated using PET. The aim was to
      account for differences in the results of two previous studies [those of Petersen
      et al. (Science 1990; 249: 1041-4) and Howard et al. (Brain 1992; 115: 1769-82)]
      by systematically varying the type of reading task and the exposure duration of
      the word stimuli. Both variables strongly influenced patterns of brain activity.
      There were three types of task: (i) reading aloud; (ii) reading silently; and
      (iii) lexical decision on visually presented words and pseudowords. Reading aloud
      and reading silently engaged the left middle and superior temporal regions,
      confirming the important role of these areas in visual word processing. The areas
      principally engaged during lexical decision were the left inferior and middle
      frontal cortices and the supplementary motor area; activity in these areas
      suggests that the subjects were using a phonological strategy to perform the
      task. There was also a significant effect of exposure duration, with activity
      being greater for short (150 ms) exposure durations than for long (1000 ms or 981
      ms) exposure durations. We conclude that until we understand how subtle
      variations in experimental design influence brain activity during reading tasks,
      the association of specific processing functions with individual anatomical areas
      activated during reading is premature.

PMID- 7820565
TI  - A graded task approach to the functional mapping of brain areas implicated in
      auditory-verbal memory.
AB  - Positron emission tomography measurements of regional cerebral blood flow (rCBF)
      were performed in normal volunteers during a graded auditory-verbal memory task.
      Subjects were required to remember and then immediately, and freely, recall a
      series of auditorily presented word lists varying from two to 13 words in length.
      Significant regional correlations between rCBF and memory load (word list length)
      were identified using statistical parametric mapping. Increasing memory load
      correlated with increasing rCBF in the cerebellar vermis and hemispheres,
      thalamus bilaterally, the superior and middle frontal gyri bilaterally, anterior
      insular regions bilaterally, anterior cingulate, precuneus and left and right
      lateral premotor areas. Increasing memory load also correlated with decreasing
      rCBF in the left and right superior temporal/insular regions, medial frontal
      gyrus, Brodmann's area 37 bilaterally, cuneus, inferior parietal lobule
      bilaterally and the mid-portion of the cingulate cortex. The pattern of rCBF
      change closely resembled that identified in a previously reported study using a
      cognitive subtraction paradigm and provides further evidence for a widespread
      neural system subserving auditory-verbal memory. The patterns of rCBF response
      suggest that the areas identified are associated with limited capacity processes
      for encoding and retrieval.

PMID- 7820566
TI  - Functional dissociations following bilateral lesions of auditory cortex.
AB  - We present two patients with bilateral lesions of the superior temporal cortex
      who manifested a number of functional dissociations in the auditory domain. The
      perception of speech and environmental sounds were preserved; yet, the perception
      of tunes, prosody and voice was impaired. As the processing of melodic but not
      rhythmic variations in musical sequences was selectively disturbed, the deficit
      cannot be attributed to a general impairment in auditory memory or sequential
      processing. These findings suggest that melody processing is not mediated by a
      general-purpose auditory architecture but by specialized cortical subsystems
      residing within the lesioned areas. Current taxonomies of auditory agnosia and
      models of normal music cognition are evaluated in light of the functional
      dissociations manifested by these patients.

PMID- 7820567
TI  - Erectile dysfunction in multiple sclerosis. Associated neurological and
      neurophysiological deficits, and treatment of the condition.
AB  - Forty-eight men with multiple sclerosis and erectile dysfunction were evaluated.
      Emphasis was placed on the neurological features and the relationship between
      impotence and the bladder dysfunction in multiple sclerosis. Erectile failure was
      invariably associated with pyramidal signs in the lower limbs and with urinary
      symptoms. All of the men with impotence and marked pyramidal dysfunction in their
      legs were found by cystometric studies to have bladder hyperreflexia. The
      severity of the urinary symptoms was related to the degree of pyramidal
      impairment in the lower limbs. The posterior tibial and the pudendal cortical
      evoked potentials were abnormal in most of the men with multiple sclerosis and
      erectile failure. However, recording the pudendal cortical responses in patients
      with multiple sclerosis and impotence provided no more information than the
      tibial cortical evoked potentials. The neurological examination findings together
      with the results of the neurophysiological and cystometric tests suggest that
      erectile dysfunction in multiple sclerosis is due to spinal lesions situated
      proximal to the sacral cord. The feasability of papaverine intracorporeal
      injection therapy for men with multiple sclerosis and impotence was assessed.
      Papaverine intracorporeal injections produced satisfactory erections in the
      majority of the impotent men. Erectile failure in patients with multiple
      sclerosis was successfully managed for up to 2 years, by intracorporeal self
      injection therapy.

PMID- 7820568
TI  - Patterns of oligodendroglia pathology in multiple sclerosis.
AB  - Patterns of inflammation, demyelination and oligodendrocyte pathology were
      studied in acute multiple sclerosis and during early and late exacerbations of
      chronic multiple sclerosis. Cells within lesions were identified by
      immunocytochemistry with markers for T lymphocytes, macrophages, oligodendrocytes
      and astrocytes. In addition, in situ hybridization for proteolipid protein mRNA
      was used to identify myelinating and myelin supporting oligodendrocytes.
      Degenerating cells in the lesions were detected by DNA fragmentation in cell
      nuclei. The inflammatory reaction in all three types of multiple sclerosis
      lesions was shown to be dominated by T lymphocytes and macrophages. In late
      chronic multiple sclerosis lesions, a significant increase in the number of
      immunoglobulin producing plasma cells was found in infiltrates as compared with
      acute and early multiple sclerosis lesions. In all three types of multiple
      sclerosis, confluent plaques of demyelination were found to be present. In acute
      multiple sclerosis, demyelination was found to be associated with extensive
      destruction of other tissue elements, including oligodendrocytes, astrocytes and
      axons, but even in these destructive lesions a considerable number of
      oligodendrocytes was preserved and at disposal therefore, for rapid
      remyelination. During early exacerbations of chronic multiple sclerosis,
      selective demyelination was associated with almost complete preservation of
      oligodendrocytes in the majority of cases. Correspondingly, a high number of
      remyelinating lesions was present at that stage of disease. In lesions developing
      late after onset of multiple sclerosis, demyelination generally accompanied
      extensive destruction and loss of oligodendrocytes. In these lesions,
      remyelination was sparse and restricted to lesional borders. The observed
      patterns of cell death suggest that in some cases oligodendrocytes, in others
      myelin sheaths are the primary target of the destructive process. Our data
      indicate that the type and amount of inflammation, de- and remyelination, and of
      tissue damage vary between different forms of multiple sclerosis and between
      different stages of the disease, possibly reflecting different pathogenic
      mechanisms in a disease spectrum.

PMID- 7820569
TI  - Multiple sclerosis. Immunomodulatory effects of human astrocytes on T cells.
AB  - Using a human culture system, we have previously shown that interferon-gamma-and
      tumour necrosis factor-alpha-stimulated astrocytes are capable of presenting
      antigens to T lymphocytes, but do not support antigen-dependent T cell
      proliferation. To gain further insight into the mechanisms involved in the local
      regulation of intracerebral T cell responses, we have investigated the effects of
      astrocytes on T cell proliferation induced by peripheral blood-derived
      mononuclear cells (PBMC). We found that astrocytes derived from human embryonic
      brain were able to suppress PBMC-dependent proliferation of antigen-specific,
      CD4+ T cell lines. Interferon-gamma production by PBMC-stimulated T cells was
      also suppressed by astrocytes, and this inhibition was seen as early as 6 h after
      initiation of co-culture. The inhibitory effect was observed in the presence of
      both HLA matched and mismatched astrocytes and was mediated by astrocyte-derived
      soluble factor(s) rather than by direct cellular contact. Inhibition of T cell
      proliferation was incompletely reverted by indomethacin, suggesting that
      prostaglandins were partially involved in the suppressive effect. The cytotoxic
      mediator nitric oxide was not involved in astrocyte-mediated inhibition. These
      observations led us to further investigate the contribution of other mediators
      known to down-regulate inflammatory processes. Our astrocyte cultures did not
      synthesize interleukin (IL)-4 or IL-10, whereas they secreted both the latent and
      active forms of transforming growth factor-beta 2. Transforming growth factor
      beta was, however, found not to participate in astrocyte-induced inhibition in
      vitro. The inhibitory properties of human astrocytes may contribute to
      confinement of inflammatory lesions in multiple sclerosis and other inflammatory
      diseases of the central nervous system.

PMID- 7820570
TI  - Myelination in vitro of rodent dorsal root ganglia by glial progenitor cells.
AB  - Oligodendrocytes synthesize myelin in the mammalian central nervous system; they
      develop from glial progenitors which, at least in vitro, are bipotential and also
      differentiate into astrocytes. Maturation of these O-2A progenitors is known to
      be influenced by growth factors and by extracellular matrix molecules. We
      investigated the effect of neurons on glial development by co-culturing highly
      purified rodent embryonic dorsal root ganglia with neonatal O-2A progenitors.
      Neurons produce signals, including platelet-derived growth factor BB and basic
      fibroblast growth factor, which stimulate progenitor cells to synthesize DNA;
      axonal contact is associated with down-regulation in the expression of complex
      ganglioside surface molecules on O-2A progenitors; with maturation, many of these
      cells develop into oligodendrocytes allowing the normal process of myelination to
      take place, but neurons also promote the differentiation of type 2 astrocytes.
      This orchestration of proliferation and differentiation in O-2A progenitor cells
      favours the development of glial-neuronal interactions needed for saltatory
      conduction of the nerve impulse.

PMID- 7820571
TI  - Central demyelination induced in vivo by the calcium ionophore ionomycin.
AB  - The effects of injecting the calcium-selective ionophore, ionomycin, into
      myelinated tracts in the dorsal columns of adult rat spinal cords were examined
      electron microscopically. In vivo, ionomycin induced a primary vesicular
      demyelination, together with a variable degree of axonal degeneration, in a dose
      dependent manner. The results are consistent with previous demonstrations that
      mature oligodendrocytes are more vulnerable to alterations in levels of [Ca2+]i
      than other glial cells. We speculate that demyelination induced by ionomycin in
      vivo occurs as a result of direct activation of endogenous Ca(2+)-dependent
      enzymes and/or as a consequence of oligodendrocyte injury mediated via
      astrocytes.

PMID- 7820572
TI  - Pathogenic factors underlying the lesions in Leigh's disease. Tissue responses to
      cellular energy deprivation and their clinico-pathological consequences.
AB  - In a search for pathogenic factors that might play roles in the selective
      vulnerability of brain regions to the lesions of Leigh's disease, archival
      material from 20 cases of this condition, dying between 1975 and 1992 and aged
      from 4 days to 11.75 years at death, have been examined. Attention was paid to
      the topography of the lesions, their nature and timing in the evolution of the
      disease, the clinico-pathological correlations and the ages of the subjects at
      onset and at death. The following observations would appear to be explicable in
      terms of the present understanding that impairment of cellular energy generation
      is known to be defective in some, and probably all, cases. (i) The characteristic
      lesion of this disease is symmetrical vasculonecrotic damage affecting several
      brainstem centres, the topography of which is variable and may partly depend upon
      the age of the individual. (ii) Early features of this lesion are
      indistinguishable from a small partial infarction and progress similarly. The
      size of the damaged area is generally related to the size of the region affected.
      There is no haemorrhagic component and haemosiderin is not at any time found,
      unlike the lesions of Wernicke's disease. (iii) The process is episodic and total
      tissue damage is thus cumulative. More than one episode of damage may be seen in
      a region, changes of clearly different ages being often present together. (iv) In
      some regions the lesions appear to be age dependent, e.g. inferior olivary
      nuclei, and may be related to behavioral development and neuronal activity. Other
      regions show damage at any age, e.g. substantia nigra. (v) Myelin and sometimes
      axon loss in optic pathways is usually central, the periphery being spared. This
      occurred in more than half the cases and may represent a partial infarct-like
      change. (vi) The characteristic dorsal spinal column degeneration is always
      associated with focal necrosis of central grey and white matter; this also
      resembles a partial infarction with secondary ascending degeneration. (vii)
      Massive myelin loss in the centra semiovalia occurred in one-third of the cases,
      with or without cavitation, often in association with spongy myelin changes
      elsewhere. A mild general spongy change in myelin alone occurred in two cases.
      The massive lesions are focal, infarct-like and analogous to Binswanger's
      disease. (viii) Selective neuronal loss, common in some mitochondrial disorders,
      is not a major feature of Leigh's disease.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7820573
TI  - Effects of cholinergic blockade on language in healthy young women. Implications
      for the cholinergic hypothesis in dementia of the Alzheimer type.
AB  - To investigate the effect of cholinergic blockade on language, 22 healthy young
      women performed tests of reading, spelling and oral language after a subcutaneous
      injection of 0.4 or 0.6 mg scopolamine. The results were compared with the
      performance after 0.6 mg methylscopolamine, which produce no central cholinergic
      effects. The reading and spelling tests were constructed to evaluate the lexical
      and phonological strategies for reading and spelling of single words. After
      scopolamine there were dose-dependent impairments in reading, spelling, verbal
      fluency and object naming. In 25-60% of the subjects receiving 0.6 mg scopolamine
      there were clinically significant impairments on tests assessing the lexical and
      phonological strategies. This pattern is similar to the deficits in reading and
      spelling observed in patients with dementia of the Alzheimer type. Cholinergic
      loss may be associated with the language impairments found in dementia of the
      Alzheimer type.

PMID- 7820574
TI  - Polyneuropathy associated with monoclonal gammopathy of undetermined
      significance. A prospective study of the prognostic value of clinical and
      laboratory abnormalities.
AB  - The natural course of polyneuropathy associated with monoclonal gammopathy of
      undetermined significance (MGUS) is not well known. We therefore studied 32
      untreated patients for a period of 5 years. Fifteen patients had an IgM M
      protein, 15 an IgG and two an IgA. There was a male predominance, a mean age of
      onset at the end of the sixth decade and sensory signs were more pronounced than
      motor deficits. On entry into the study and during the 5 years of follow-up, we
      quantified the neuropathy in a standard way: totals of motor and sensory scores;
      vibration perception threshold; tapping tests; quantified Romberg test;
      electrophysiological parameters. A significant difference in the natural history
      between the polyneuropathy associated with IgM-MGUS and IgG/IgA-MGUS was found
      for the motor and sensory sum scores, the vibration perception threshold and the
      tapping tests. The polyneuropathy in IgM-MGUS is more progressive, with
      significantly more weakness and sensory signs, indicating that the neuropathies
      associated with IgM-MGUS and IgG/A-MGUS may be two different entities. A rapid
      progression of the neuropathy was found in five patients. We found no predictive
      factors for this severe progression of the neuropathy of these five patients. Of
      these five, three (two IgM, one IgG) developed a non-Hodgkin lymphoma.

PMID- 7820575
TI  - Vascular and metabolic factors in the pathogenesis of experimental diabetic
      neuropathy in mature rats.
AB  - The complex interrelationships between metabolic factors (increased nerve
      glucose, fructose and sorbitol and decreased nerve myo-inositol levels) and
      ischaemic-hypoxic vascular factors [decreased nerve blood flow (NBF) and
      increased nerve vascular resistance (NVR)] in the pathogenesis of diabetic
      neuropathy are incompletely understood. This study evaluates, in mature animals,
      the time course and magnitude of changes in factors postulated to be of
      importance in the pathogenesis of experimental diabetic neuropathy (EDN).
      Hyperglycaemia was induced in mature 9-month-old male Sprague-Dawley rats with
      streptozocin (as in studies utilizing immature rats it has been difficult to
      separate effects which are due to the growth retardation and maturational delay
      induced by hyperglycaemia from those arising from diabetes per se). Groups of age
      matched control and diabetic animals were compared 1, 2, 4, 8, 16 and 24 weeks
      after injection. In diabetic animals NBF was decreased and NVR was increased
      after 1 week (P < 0.05); sciatic nerve glucose, sorbitol and fructose levels were
      increased after 1 week (P < 0.05). These changes were maintained for the duration
      of the experiment. Sciatic and caudal nerve conduction velocities were
      significantly decreased after 16 weeks (P < 0.05), although trends were apparent
      after 4 weeks. Diabetic animals showed decreased sciatic nerve myo-inositol
      levels between 2 and 16 weeks (P < 0.05), but there was no significant difference
      at 24 weeks. There were no significant differences in sciatic nerve total
      (Na+K+)ATPase concentrations. Early and sustained alterations in vascular indices
      (NBF and NVR) support the postulate that ischaemic-hypoxic factors may play a
      role in the causation of EDN. The ischaemic-hypoxic postulates do not, however,
      diminish the obvious importance of the multitude of metabolic alterations which
      also occur very early after the onset of hyperglycaemia.

PMID- 7820576
TI  - Acute effects of levodopa on wrist movement in Parkinson's disease. Kinematics,
      volitional EMG modulation and reflex amplitude modulation.
AB  - Acute changes in motor performance due to levodopa were evaluated by a series of
      four motor tests unified by their focus on wrist flexion-extension movements.
      Subjects with idiopathic Parkinson's disease were evaluated with this battery of
      tests before (OFF) and after their usual morning dose of levodopa (ON). The test
      battery consisted of (i) repetitive self-paced movement in which velocity was to
      be maximized; (ii) visually guided tracking of a sinusoid and a square wave; and
      (iii) an assay of stretch reflex modulation during volitional sinusoidal
      tracking. The maximal wrist joint velocity of self-paced reciprocating flexion
      and extension movements increased after levodopa (ON), without significant
      changes in the movement period or amplitude. In the two tracking tasks, some
      subjects improved as evident by a lower root mean square (rms) error, but in
      similar numbers of subjects the rms error increased. Overall, the rms error, peak
      velocity or peak movement amplitude did not change after levodopa in either
      tracking task. Significant and consistent changes did occur after levodopa in an
      assay of reflex modulation during error-constrained tracking (Johnson et al.,
      Brain 1991; 114: 443-60). The amplitude of volitional EMG increased after
      levodopa, with a concurrent reduction in reflex EMG. These changes are consistent
      with the noted increase in movement velocity. These results show that the effects
      of levodopa on movement velocity were not consistently translated into increased
      accuracy. The changes in the long latency reflex gain argue for a central control
      of this reflex, mediated by structures sensitive to levodopa. Finally, the
      results show that the quantitative evaluation of levodopa therapy cannot be
      unidimensional, but requires a battery of motor tests as undertaken in this
      study.

PMID- 7820577
TI  - Vestibular, cervical and visual remembered saccades in Parkinson's disease.
AB  - In order to assess both vestibulo-cervical perception of head rotation and
      saccadic function in Parkinson's disease, 14 patients with idiopathic Parkinson's
      disease were subjected to discrete sigmoid-shaped rotational displacements whilst
      fixating a target aligned with primary gaze in an otherwise dark room. The
      rotational stimuli were applied to (i) the whole body (vestibular stimulus); (ii)
      the trunk whilst the head remained stationary in space (cervical stimulus); (iii)
      to the head alone whilst the trunk remained stationary (combined vestibular and
      cervical stimulus). The fixation target was then extinguished and the subjects
      had to estimate the angle travelled by the head or trunk with an ocular-pointing
      task using information from the preceding rotational stimulus (vestibular and
      cervical 'remembered' saccades). It was found that, although these saccades in
      Parkinson's disease patients were multiple-step and hypometric, the final
      position of the eyes matched the rotational stimulus as accurately as in normal
      subjects. A complementary experiment in six patients showed that visual
      remembered saccads were hypometric, but significantly less so than vestibular
      remembered saccades. It is concluded that (i) vestibular and cervical perception
      of head/neck rotation is normal in Parkinson's disease; (ii) abnormalities of
      'remembered' saccades, previously reported in Parkinson's disease, are not
      confined to the visual modality but involve other sensory modalities as well;
      (iii) across different modalities of memory-guided saccades, visual input
      improves saccadic performance. This result demonstrates that the known increased
      visual dependence found in Parkinson's disease extends to memory-driven tasks.

PMID- 7820578
TI  - Disturbances of kinaesthesia in patients with cerebellar disorders.
AB  - We studied the ability of patients with cerebellar degeneration to perceive
      differences in kinaesthetic stimuli and compared it with that of normal subjects.
      All participants were tested for duration, amplitude and velocity sensation. In
      separate experiments, the responses of muscle spindle afferents and slowly
      adapting cutaneous mechanoreceptors to the kinaesthetic stimuli were recorded.
      The performance of patients with cerebellar degeneration was significantly worse
      than that of normal subjects on the tasks testing for duration and velocity
      perception. Although both spindle afferents and slowly adapting cutaneous
      mechanoreceptors were able to provide relevant sensory information during the
      kinaesthetic tasks, spindle afferents were superior in detecting velocity
      changes. These results suggest that the cerebellum may be involved in processing
      sensory signals that are involved in motor control as well as in conscious
      perception.

PMID- 7820579
TI  - A quantitative assessment of presynaptic inhibition of Ia afferents in spastics.
      Differences in hemiplegics and paraplegics.
AB  - Soleus H-reflex facilitation evoked by a supramaximal conditioning stimulation to
      the femoral nerve was investigated in 28 healthy control subjects and 35 spastic
      patients of whom 17 were paraplegics with bilateral spinal cord lesion and 18
      were hemiplegics with unilateral cerebral lesion. Heteronymous facilitation from
      quadriceps to soleus was measured 0.4 ms after onset, while the monosynaptic Ia
      excitation is still uncontaminated by any non-monosynaptic effect and can be used
      to assess ongoing presynaptic inhibition on Ia terminals to soleus motor neurons.
      In paralegics, this heteronymous Ia facilitation was significantly larger than in
      control subjects (all individual results in these patients being above the mean
      observed in controls). This must reflect a decrease in presynaptic inhibition of
      Ia terminals in the paraplegics explored here. There was no correlation between
      this decreased presynaptic inhibition of Ia terminals and the degree of
      spasticity measured by Ashworth's scale. Surprisingly, the amount of heteronymous
      Ia facilitation in hemiplegics was the same as in normal subjects. This indicates
      that presynaptic inhibition of Ia terminals is unchanged in these patients and
      disagrees with the usual interpretation of reduced vibratory inhibition of the
      soleus H-reflex in hemiplegics. It is argued that this disagreement is due to the
      fact that vibratory inhibition of the reflex also depends on post-activation
      depression following repetitive synaptic transmission.

PMID- 7820580
TI  - Abnormal eye movements in blepharospasm and involuntary levator palpebrae
      inhibition. Clinical and pathophysiological considerations.
AB  - We report on four patients with involuntary eyelid closure and eye movement
      disorders. Three were healthy until the onset of their illness and one had a mild
      generalized choreoathetosis and dystonia due to kernicterus. Electromyographic
      recording revealed solely blepharospasm in two patients and blepharospasm in
      combination with involuntary levator palpebrae inhibition in the other two. The
      eye movement abnormalities were clinically characterized by inability to fix gaze
      and short or prolonged episodes of uncontrollable eye deviations accompanied, in
      two patients, by diplopia in horizontal or vertical directions. These episodes
      occurred independently of a disorder of eyelid movement. Eye movement recordings
      with a double magnetic induction technique showed saccadic intrusions in
      horizontal directions. They consisted of highly frequent square wave jerks in
      three and sporadic macro-square wave jerks in two patients. There were also
      episodes of extraocular muscle dystonia, commonly known as oculogyric crises,
      resulting in involuntary upward eye deviation in all patients and lateral
      deviation in three patients. In one patient, nasal-ward deviations were sometimes
      restricted to one eye. We conclude that these abnormal eye movements do not
      necessarily point to a symptomatic form of dystonia and that they may limit the
      beneficial effect of botulinum toxin or surgical intervention in the therapeutic
      management of involuntary eyelid closure. We suggest that either basal ganglia,
      especially substantia nigra pars reticularis and the brainstem structures,
      especially the paramedian pontine reticular formation, or both, may be involved
      in the pathogenesis of these abnormal movements.

PMID- 7820581
TI  - The interpretation of pain relief and sensory changes following sympathetic
      blockade.
AB  - A comparative study of the effects of sympathetic blockade by stellate ganglion
      block (SGB) and intravenous phentolamine infusion (PhI) was carried out in 24
      patients with presumed sympathetically maintained pain of an upper extremity. A
      total of 15 SGBs and 16 PhIs were performed, with seven patients undergoing both
      procedures. All patients developed a Horner's syndrome with SGB and nasal
      stuffiness and cardiovascular changes with PhI. Similar pain relief was obtained
      with SGB and PhI in six of the seven who underwent both procedures. Pre-procedure
      patient characteristics including age, sex, duration of pain, historical and
      physical examination features suggestive of the reflex sympathetic dystrophy
      syndrome, and sensory disturbances such as allodynia and hyperpathia did not
      predict pain relief from either procedure. Changes in skin temperature following
      the sympatholytic procedure did not correlate with pain relief. For PhI, pain
      relief correlated with the magnitude of decrease in systolic blood pressure.
      After SGB, changes in quantitative thermal sensory testing (QST) suggestive of a
      partial deficit in thermal sensation correlated with pain relief. In 20 normal
      controls, water bath immersion to cool the hand passively by 7 degrees C and warm
      the hand passively by 4 degrees C had small and selective effects on thermal QST
      thresholds, but did not produce a general impairment in thermal sensation. In
      conclusion, the diagnosis of sympathetically maintained pain based on the history
      and physical examination alone cannot be made with confidence and therefore a
      sympatholytic procedure is necessary. When SGB produces pain relief but PhI does
      not, systemic absorption of local anaesthetic and/or sensory blockade by spread
      to somatic nerves may be the reason. Thus, PhI appears to be a less sensitive but
      more specific test than SGB. These two procedures provide complementary
      information and both may be needed to establish the diagnosis of sympathetically
      maintained pain.

PMID- 7820582
TI  - Fimbria-fornix lesions impair spatial performance and induce epileptic-like
      activity but do not affect long-term potentiation in the CA1 region of rat
      hippocampal slices.
AB  - Groups of rats were given bilateral fimbria-fornix lesions and one month later
      grafted into the hippocampus with fetal cholinergic and non-cholinergic
      (hippocampal) neural tissue. Three weeks and 3 months after transplantation the
      animals were trained to find and then to retain the location of a hidden platform
      in the Morris water maze. After the final behavioral testing phase,
      electrophysiological studies of the short- and long-term potentiation (STP and
      LTP) and epileptiform activity of evoked responses were performed in vitro in the
      CA1 region of the hippocampus. The lesions produced a marked deficit in spatial
      function in the early testing phase which showed some recovery at the three month
      time point. Neither the cholinergic nor the non-cholinergic grafts improved
      spatial performance; indeed, on some measures these groups showed a significantly
      greater deficit than the lesion-alone group. Epileptiform activity, which was
      defined as the ratio of the sum of amplitudes of second and third population
      spikes to the amplitude of the first, before tetanization was not significantly
      different for all groups. After tetanization of the radiatum input, however, the
      epileptiform activity in the FFL group was significantly higher in comparison to
      that of the control groups. Grafting of cholinergic tissue decreased this
      parameter to the control level, but non-cholinergic grafts did not modify the
      lesion-induced epileptiform activity. Epileptiform activity after tetanization of
      the oriens input was approximately equal for all groups. There were no
      significant differences between surgical groups in STP and LTP for both the
      oriens and radiatum inputs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7820583
TI  - Intracerebroventricular injection of interleukin-1 beta enhances nociceptive
      neuronal responses of the trigeminal nucleus caudalis in rats.
AB  - To assess the effect of interleukin-1 (IL-1) in the brain on nociception
      electrophysiologically, recombinant human IL-1 beta (rhIL-1 beta) (1 pg/kg to 1
      microgram/kg, i.e., 0.29 pg-0.33 microgram/rat) was microinjected into the
      lateral cerebral ventricle of urethane-anesthetized rats and the changes of
      responses in the wide dynamic range (WDR) neurons in the trigeminal nucleus
      caudalis to noxious pinching of facial skin were observed. A significant
      enhancement in the responses of the WDR neurons to noxious stimuli was observed
      after the injection of rhIL-1 beta between 10 pg/kg and 1 ng/kg, which showed a
      maximal response at a dose of 100 pg/kg (29-33 pg/rat) which began to appear 5
      min after injection, reached a peak within 25 min and then gradually subsided.
      However, this dose of rhIL-1 beta did not affect the responses of low threshold
      mechanoreceptive neurons to skin brushing. An increase in the dose of rhIL-1 beta
      by more than 10 ng/kg (up to 1 microgram/kg) had no effect on the nociceptive
      responses of the WDR neurons. The rhIL-1 beta-induced enhancement of nociceptive
      responses of WDR neurons was completely abolished by pretreatment with either IL
      1 receptor antagonist, Na salicylate or alpha-melanocyte stimulating hormone.
      These results therefore provide electrophysiological evidence that IL-1 beta
      which is produced in the brain induces hyperalgesia in the rat.

PMID- 7820584
TI  - Alpha-, beta II- and gamma-subspecies of protein kinase C localized in the monkey
      hippocampus: pre- and post-synaptic localization of gamma-subspecies.
AB  - Protein kinase C (PKC) has attracted wide attention as a key enzyme for the
      expression of long-term potentiation in the hippocampus, a basic model for
      memory. It is of interest to study the detailed localization of PKC subspecies in
      the monkey hippocampus. We used immunocytochemistry to examine the localization
      of PKC subspecies in the hippocampus of the monkey, Macaca mulatta. Subspecies of
      PKC in the monkey could be separated by hydroxyapatite chromatography and the
      elution profile proved to be similar to that of the rat. Antibodies against each
      alpha, beta II and gamma-subspecies of the rat specifically reacted with the
      respective subspecies of monkey PKC. The alpha-, beta II- and gamma-subspecies
      were distinctly distributed in the hippocampus. The beta I-subspecies was not
      evident in the hippocampus. While both the alpha- and gamma-subspecies
      immunoreactive pyramidal cells were distributed throughout the hippocampus (CA1
      CA3), the beta II-subspecies immunoreactive cells were scattered only in the CA1
      region. The gamma-subspecies was found in granule cells and dendrites in the
      dentate gyrus, in mossy fibers and in their terminals in the CA3 region. The
      alpha-subspecies was also present in granule cells and in the dendrites but not
      in the mossy fibers. Glial cells did not stain with any of the antibodies used.
      Electron microscopy clearly showed that the gamma-subspecies was localized in
      both presynaptic terminals and post-synaptic dendrites. These observations
      suggest that subspecies of PKC in the monkey hippocampus may be involved in
      distinct functions and that the gamma-subspecies of PKC may act pre- and post
      synaptically in pyramidal cells of the hippocampus.

PMID- 7820585
TI  - Effect of administration of 3-acetylpyridine followed by niacinamide injection on
      survival, extent of the inferior olivary complex lesion, and response to
      harmaline in the young rat.
AB  - In the 15 day-old DA/HAN strained rat, i.p. injection of 3-acetylpyridine (3-AP)
      50, 65 or 95 mg.kg-1 was followed 2 to 4 hours later by administration of
      niacinamide (300 mg.kg-1). The percentage of survival and the extent of the
      inferior olivary complex (IOC) lesion, determined histologically, were correlated
      with both the dose of 3-AP administered and the time delay between 3-AP and
      niacinamide injections. Moreover, the tremor elicited by harmaline was also
      correlated with the extent of the IOC lesion. The results show that it is more
      advantageous to administer 95 mg.kg-1 3-AP and to delay niacinamide injection by
      2h30 or less to get the higher percentage of survival (about 90%) and a
      reasonably high percentage of totally IOC lesioned rats (more than 30%). They
      also demonstrate that the harmaline test is not sufficient to acutely judge of
      the extent of the IOC lesion and that, in all cases, histological controls have
      to be done. The results are discussed in terms of interrelationships of the
      variable studied.

PMID- 7820586
TI  - Neuronal activity in normal and deafferented forelimb somatosensory cortex of the
      awake cat.
AB  - Three hundred and seventy-three neurons were recorded from the forelimb
      representation in the primary somatosensory cortex of unanesthetized, quietly
      resting adult cats. Of these, 177 were studied from 2 days to 3 weeks after
      transection of the radial, median and ulnar nerves. Following deafferentation the
      proportion of cells without receptive fields increased from 24 to 82%, however,
      the average rate of spontaneous activity did not change nor did the probability
      of encountering a neuron with a receptive field as a function of depth. Receptive
      field sizes increased dramatically following deafferentation and the response
      changed from a reliable short-latency, brisk discharge to one that did not occur
      on every stimulus. After deafferentation the edges of the receptive field often
      could not be defined accurately. Spontaneous activity in 31% (n = 47) of the
      neurons from deprived cortex could be modulated by manipulations of the body but
      these changes were sufficiently slow and ill-defined that they were not
      classified as a receptive field. In some cases, manipulation of the body
      gradually reduced the discharge rate. This slow decline in activity was different
      from the abrupt inhibition of spontaneous activity elicited by somatic stimuli in
      another class of cells (n = 18). In other cases the manipulation produced a
      gradual increase in the discharge rate. After deafferentation antidromically
      identified corticothalamic and pyramidal tract neurons did not display behaviors
      different from their counterparts in normal cortex. However, the mean latency for
      synaptic activation from the ventroposterior thalamus increased from 2.7 ms to
      4.6 ms. The lost forelimb receptive fields were rarely replaced by inputs from
      adjacent body parts over the two-week duration of this study. Most responses to
      somatic stimuli obtained from cortical neurons in the deafferented cortex were
      clearly abnormal.

PMID- 7820588
TI  - Prenatal exposure to ethanol induces changes in the nerve growth factor and its
      receptor in proliferating astrocytes in primary culture.
AB  - We have analyzed the effect of prenatal exposure to alcohol on the binding,
      internalization and secretion of NGF as well as on the content of the NGF
      receptor (NGFr) in cortical rat astrocytes in primary culture. Secretion of NGF
      was approximately 1.8-fold greater in 6-day control astrocytes than in 13-day
      cells. Intracellular content of NGF was very low. Astrocytes in 6-day cultures
      from control fetuses expressed a relatively large number of NGFr on the cell
      surface with a steady-state constant in the low nanomolar range. NGF was
      internalized by astrocytes at a slow rate. Prenatal exposure to ethanol induces a
      moderate increase in the number of NGFr on the cell surface as well as an
      increase in the intracellular pool of both NGF and NGFr which is accompanied by
      an important reduction in the secretion of this factor. We speculate that this
      decrease in NGF secretion could alter the neuronal migration pattern during
      development, resulting in the presence of ectopic neurons in the cortex.

PMID- 7820587
TI  - Effects of chronic food restriction on mu and kappa opioid binding in rat
      forebrain: a quantitative autoradiographic study.
AB  - It was previously observed that chronic food restriction lowers the threshold for
      lateral hypothalamic self-stimulation in a manner that is reversible by mu- and
      kappa-selective opioid antagonists. The present quantitative autoradiographic
      study was designed to investigate whether chronic food restriction alters
      regional mu and kappa opioid binding in brain. [3H]DAGO (mu) and mu/delta blocked
      [3H]BMZ (kappa) binding were analyzed in 34 brain regions from the medial
      prefrontal cortex to posterior hypothalamus. Significant reductions in mu binding
      were observed in caudal portions of the medial and lateral habenula, and the
      basolateral and basomedial nuclei of the amygdala. kappa binding was similarly
      reduced in medial habenula. Large increases in kappa binding were observed in the
      bed nucleus of the stria terminalis, ventral pallidum, and medial preoptic area.
      The possible involvement of these changes in the sensitization of reward by food
      restriction is discussed.

PMID- 7820589
TI  - Potassium currents in epilepsy: effects of the epileptogenic agent
      pentylenetetrazol on a cloned potassium channel.
AB  - The effect of the epileptogenic agent pentylenetetrazol (PTZ) on the cloned rat
      brain potassium channel Kv1.1 (labelled also RCK1) was investigated in the
      Xenopus laevis oocyte expression system. The Kv1.1 channel was affected by PTZ in
      a voltage-dependent manner. PTZ increased the potassium currents at more negative
      potentials and decreased them at more positive potentials. At a potential of -50
      mV the potassium currents were increased by 0.97 and at -20 mV decreased by 0.21
      of control value with 100 mmol/l PTZ. The potential at which the inversion from
      increase to decrease occurred was -33 mV. The inactivation characteristic of the
      current was shifted to more negative potentials by PTZ. The PTZ effect was
      obtained at a threshold concentration of 1 mmol/l and increased with rising PTZ
      concentrations. After removal of the tissues covering the oocyte membrane, the
      PTZ effect was augmented; with a concentration of 10 mmol/l PTZ the potassium
      currents at 0 mV were decreased by 0.04 in oocytes with covering tissues and by
      0.27 of control value in oocytes without covering tissues. Under current-clamp
      conditions, PTZ decreased small depolarizations and increased larger
      depolarizations. This effect of PTZ represents a 'discriminatory function' that
      may contribute to epileptogenesis in nervous tissues.

PMID- 7820590
TI  - Dentate granule cells as a central cardioregulatory site in the rat.
AB  - Dentate granule cells can be selectively destroyed by intrahippocampal injections
      of colchicine. This study evaluates the consequences of granule cell destruction
      on blood pressure regulation in the normotensive Wistar-Kyoto (WKY) and
      spontaneously hypertensive rat (SHR). Bilateral destruction of dentate granule
      cells at 6 weeks of age produced a significant increase in blood pressure in the
      WKY that lasted for approximately 3 weeks, and a biphasic effect (increase then
      decrease) in the SHR that resulted in a significant hypotensive period that
      persisted for 6 weeks. Granule cell destruction at 11 weeks produced a maximal
      hypertension in the SHR that preceded age-matched controls by 4 weeks, but
      produced only a small transient increase in WKY blood pressure. Dentate granule
      cells are the exclusive source of prodynorphin-derived peptides in the
      hippocampal formation and their synthesis is regulated by glucocorticoids.
      Evidence suggests glucocorticoids may be involved in the regulation of blood
      pressure and hypertension. We determined that chronic high levels of
      corticosterone significantly reduced hippocampal dynorphin B levels in
      normotensive Sprague-Dawley rats. In addition, we confirmed that naive SHRs also
      contain significantly lower levels of hippocampal dynorphin B. These results
      suggest (i) that dentate granule cells represent a discrete neural site that may
      exert a tonic inhibitory influence on blood pressure, (ii) that dentate granule
      cells are not required for the full expression of hypertension in the SHR, and
      (iii) that chronic high levels of corticosterone can reduce dynorphin B levels in
      the dentate granule cells of normotensive rats.

PMID- 7820591
TI  - Serotonergic inhibition of extracellular glutamate in the suprachiasmatic nuclear
      region assessed using in vivo brain microdialysis.
AB  - In previous studies, we showed that localized perfusion of the SCN region with
      serotonin (5-HT) or the non-selective serotonergic, quipazine, using the
      microdialysis technique significantly reduced the extracellular concentration of
      the excitatory amino acid (EAA), glutamate. The present investigation was
      undertaken to extend these findings by characterizing the effects of various
      classes of 5-HT receptor ligands on the extracellular glutamate concentration in
      the SCN. Localized SCN application or i.p. injection of the 5-HT1A receptor
      agonist, 8-OH-DPAT, during the dark phase (6 h after lights-off) significantly
      reduced the extracellular glutamate concentration in the SCN region from baseline
      levels (38.7 +/- 8.7 and 53.4 +/- 11.2%, respectively, of pretreatment values; P
      < 0.05). The effect of systemically applied 8-OH-DPAT was abolished by i.p.
      injection of the 5-HT1A receptor antagonist, NAN-190, administered 20 min before
      the 8-OH-DPAT. Localized perfusion of the SCN with the 5-HT1B receptor agonist,
      TMFPP, also reduced extracellular glutamate but to a lesser degree than 8-OH-DPAT
      (80.1 +/- 3.9% of pretreatment levels; P < 0.05). This effect was prevented by
      i.p. injection of the non-selective 5-HT receptor antagonist, metergoline 20 min
      before TFMPP perfusion. Localized perfusion of the SCN region with the 5-HT2 and
      5-HT3 receptor agonists, alpha-methyl 5-HT and 1-phenylbiguanide, respectively,
      had little effect on extracellular glutamate (both P > 0.1 vs. baseline).
      Systemic treatment with NAN-190 alone had little effect on extracellular
      glutamate, however, similar treatments with metergoline or the 5-HT2 receptor
      antagonist, ritanserin, induced significant increases extracellular glutamate
      levels.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7820592
TI  - Multiple effects of long-term morphine treatment on postsynaptic beta-adrenergic
      receptor function in hippocampus: an intracellular analysis.
AB  - We previously reported that beta-adrenergic receptors are increased in cerebral
      cortex and hippocampus in rats treated chronically with morphine and subsequently
      down-regulated after morphine withdrawal [22,23]. The changes in receptor density
      in hippocampus were accompanied by a corresponding super- and subsensitivity,
      respectively, in beta-adrenergic responsiveness, as assessed
      electrophysiologically by measuring the ability of isoproterenol to augment
      population spike responses in the slice. In this study, we compared the ability
      of isoproterenol to reduce the Ca(2+)-activated K+ slow afterhyperpolarization
      (slow AHP) in pyramidal neurons in hippocampal slices from opiate-naive and
      chronic morphine-treated rats to determine whether such changes in beta
      adrenergic receptor function are localized postsynaptically. Chronic treatment of
      rats with morphine produced a 3.5-fold parallel shift to the left in the
      concentration-response curve for isoproterenol and reduced the EC50 from 4.8 +/-
      1.3 to 1.4 +/- 0.5 nM. In contrast, sensitivity and maximal responsiveness to
      isoproterenol was markedly decreased in pyramidal neurons recorded in slices from
      morphine withdrawn animals. The concentration-response curves for inhibition of
      the slow AHP by carbachol or forskolin were not affected by chronic morphine
      treatment. However, blockade of the slow AHP by forskolin was significantly
      reduced in pyramidal neurons studied after morphine withdrawal. These data
      suggest that the increase in electrophysiological responsiveness to beta
      adrenergic receptor stimulation found in hippocampus after chronic morphine
      treatment most likely resulted from an up-regulation in postsynaptic membrane
      receptors, whereas alterations occurring beyond the receptor level may be
      involved in the desensitization that is associated with morphine withdrawal.

PMID- 7820593
TI  - Intracellular recording from sympathetic preganglionic neurons in cat lumbar
      spinal cord.
AB  - Sympathetic preganglionic neurons (SPN) are responsible for the control of many
      autonomic targets including the heart and blood vessels. Previous intracellular
      studies have examined the morphology of SPN in the thoracic spinal cord, but
      there are no intracellular studies of SPN in the lumbar spinal cord. In this
      study we identified lumbar SPN using intracellular recording and dye-filling so
      that we could study their entire soma-dendritic tree, as well as their axons. At
      the same time, axonal conduction velocity was measured, and any evidence of an
      input in phase with phrenic nerve discharge was noted. Intracellular recordings
      were made from SPN in the L3 (n = 125) and T3 (n = 17) segments of the cat spinal
      cord. Axonal conduction velocities ranged from 0.6-8.4 m/s. In 85 lumbar SPN, the
      recordings lasted long enough to assess respiratory-related modulation. A
      respiratory-related modulation of the membrane potential was seen in 7 of these
      85 neurons. All 7 respiratory-related neurons had a conduction velocity of 2.0
      m/s or less, while none of the SPN with conduction velocities of more than 2.0
      m/s had a respiratory rhythmicity. Histological analysis of 50 biocytin-filled
      SPN, including 3 with a respiratory-related modulation of their membrane
      potential, revealed that they occurred mostly in the principal part of the
      intermediolateral cell column and tended to be elongated in the rostro-caudal
      direction. Dendrites ramified in the intermediolateral cell column, the
      dorsolateral white matter and the ventral and medial gray matter. Axons arose
      either from cell bodies or from primary dendrites and did not bifurcate or have
      varicose intraspinal collaterals. This is the first report of the morphology of
      intracellularly filled SPN in the lumbar spinal cord.

PMID- 7820594
TI  - Correlative light and electron microscopy studies of PrP localisation in 87V
      scrapie.
AB  - The transmissible neurodegenerative diseases, of which scrapie is the archetype,
      are caused by unconventional infectious agents. Prion protein (PrP), a widespread
      host coded, cell surface sialoglycoprotein, is thought to be an essential or,
      controversially, sole component of these agents. During infection, disease
      specific accumulations of PrP may be observed in immunostained brain sections of
      mice infected with the 87V scrapie strain as amyloid plaques or as diffuse or
      granular foci within the neuropil. Using serial light and electron microscopical
      preparations we determined immunocytochemically that infection specific PrP is
      present in amyloid fibrils, and accumulates on the plasmalemma of neurites at the
      periphery of plaques and in the neuropil, irrespective of the morphological form
      of PrP accumulation when viewed by light microscopy. In some brain areas with
      dense granular PrP expression complete disruption of neuropil with loss of
      neurites was associated with fibrils lying free in expanded extracellular space.
      These results suggest that normal PrP may be converted to its pathological form
      at the neuronal plasmalemma or in the extracellular space and, furthermore, that
      amyloid fibrils are formed following the accumulation and aggregation of subunit
      proteins at these sites.

PMID- 7820595
TI  - Role of cell adhesion molecules in brain injury after transient middle cerebral
      artery occlusion in the rat.
AB  - Activated neutrophils appear to be directly involved in tissue injury after focal
      cerebral ischemia and reperfusion. Intercellular adhesion molecules-1 (ICAM-1)
      and CD11/CD18 integrins have been implicated in ischemia-reperfusion induced
      neutrophil endothelial adhesion and transmigration. We therefore investigated the
      roles of CD11a/CD18 (LFA-1) and ICAM-1 in cerebral ischemia-reperfusion injury by
      using monoclonal antibodies, WT1 (anti-CD11a), WT3 (anti-CD18), and 1A29 (anti
      ICAM-1). Rats were subjected to 1 h of middle cerebral artery occlusion (MCAO).
      Individual antibodies were administered at a dose of 5 mg/kg intraperitoneally at
      15 min before ischemia and immediately after reperfusion. Rats were killed at 24
      h after reperfusion, and brain edema, neutrophil infiltration and infarct size
      were measured. Sustained enhancement of ICAM-1 expression on capillaries was
      observed up to 24 h (beginning between 1 and 3 h after reperfusion). While,
      leukocytes began to infiltrate into the ischemic hemisphere between 6 and 12 h
      after reperfusion. Treatment with individual antibodies against cell adhesion
      molecules reduced edema formation and infarct size in addition to neutrophil
      accumulation 24 h after reperfusion. These results strongly implicate the
      invasion of neutrophils in the development of post-ischemic brain injury, and
      suggest that interactions between CD11a/CD18 and ICAM-1 contribute to neutrophil
      infiltration into the ischemic brain.

PMID- 7820597
TI  - Dynamic morphology of the synaptic junctional areas during aging: the effect of
      chronic acetyl-L-carnitine administration.
AB  - The ultrastructural features of hippocampal synaptic contact zones have been
      investigated by means of computer-assisted morphometry in rats of 6, 12 and 22
      months of age and in age-matched animals chronically treated with ALCAR at a
      daily dose of 50 mg/100 g body weight from the age of 1 month up to the day of
      sacrifice. The number of synapses/microns 3 (Nv), the average size of the
      junctional areas (S) and the total area of the synaptic contact zones/microns 3
      (Sv) were measured in tissue samples stained by means of the ethanol
      phosphotungstic acid (E-PTA) preferential technique for synaptic membranes. In
      control animals Nv was constant between 6 and 12 months of age, but significantly
      decreased in 22-month-old rats; S did not show significant differences due to
      age; Sv was unchanged between 6 and 12 months, but it decreased significantly in
      the old animals. In ALCAR treated rats Nv increased and S decreased significantly
      vs. Age-matched controls. Sv showed a lifespan constancy among the groups of age
      analysed. In ALCAR treated rats the number of contact areas smaller than 0.08
      micron 2 increased by 18, 9 and 10% at 6, 12 and 22 months of age, respectively.
      ALCAR administration resulted in a lifespan modulation of synaptic structural
      dynamics. A proper metabolism at nerve terminals is accounted to play a crucial
      role in synaptic remodelling potential: on the basis of current research data, it
      is suggested that ALCAR may improve neuronal bioenergetic mechanisms.

PMID- 7820596
TI  - Somato-sympathetic reflex transmission in the ventrolateral medulla oblongata:
      spatial organization and receptor types.
AB  - Tonic sympathetic activity in vivo is continuously modulated by inhibitory and
      excitatory reflex mechanisms. We studied the properties of somato-sympathetic
      excitatory reflex transmission in the rostral ventrolateral medulla (RVLM) of
      baroreceptor-denervated and vagotomized chloralose-anesthetized cats. Electrical
      stimulation of the left intercostal nerve of the 4th thoracic segment (IC-T4)
      elicited an early spinal and a late supraspinal reflex in the ipsilateral white
      ramus T3 from which recordings were made. Bilateral cooling of the ventral
      surface of the RVLM reversibly reduced the supraspinal reflex amplitude to 18.0
      +/- 3.1% of control (100%). The spinally evoked reflex was enhanced to maximally
      154.7 +/- 5.3%. Cooling of only the ipsilateral side of the RVLM was nearly
      equieffective in both, suppressing the supraspinal and enhancing the spinal
      reflex component. In contrast, cooling of the contralateral side had no
      significant effects on supraspinal reflex transmission but caused slight
      increases of the spinal reflex amplitudes. Similar effects were obtained by
      microinjection (RVLM) of the glutamate antagonist kynurenic acid (5 x 10(-3) M, n
      = 7) and the specific non-NMDA receptor antagonist CNQX (4 x 10(-3) M, n = 4)
      which, however, blocked the supraspinal reflex less effectively. These results
      demonstrate that the RVLM represents an essential relay in the transmission of
      both somatosympathetic reflex components. The experiments further suggest an
      almost completely ipsilateral neuronal pathway for the supraspinal reflex
      component which projects from the RVLM to the intermediolateral cell column
      (IML). The descending inhibition of the spinal reflex, however, receives neuronal
      inputs from the contralateral side.

PMID- 7820598
TI  - Activation of shivering and non-shivering thermogenesis by electrical stimulation
      of the lateral and medial preoptic areas.
AB  - Experiments were conducted to determine if the area of stimulation within the
      preoptic area and/or the magnitude of the electrical stimulus applied to the
      preoptic region would selectively alter the evoked thermogenic responses of
      normothermic and hypothermic rats. Urethane anesthetized male, Long-Evans rats
      kept at 37 degrees C, and later cooled to 34 degrees C, were given unilateral
      electrical stimulation (0.5 ms pulses of 200 microA at 50 Hz for 30 and 300 s)
      into either the medial preoptic area (MPO) or the lateral preoptic area (LPO).
      Temperature changes of intrascapular brown adipose tissue, TIBATs; of
      gastrocnemius muscle, Tms, tail, Tts and colonic Tcs via thermistor probes were
      recorded before and after stimulation along with differential, multi-unit EMG
      activity of the gastrocnemius muscle via implanted stainless steel electrodes.
      The group kept at 37 degrees C and given MPO electrical stimulations evoked
      graded increases in TIBATs above core dependent on the duration of the electrical
      stimulus but shivering did not occur and Tms did not rise. When kept at 34
      degrees C the MPO-stimulated group showed greater increases in TIBATs than
      respective responses seen when the same stimuli were applied at 37 degrees C. The
      group maintained at 37 degrees C and given LPO stimuli over 300 s increased Tms
      as shivering occurred, yet no change in TIBATs were observed. When cooled to 34
      degrees C LPO stimulation (30 or 300 s duration) showed greater shivering
      activity. Interesting, LPO stimulation of animals maintained at 34 degrees C also
      caused TIBAT to increase.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7820599
TI  - Bovine serum albumin selectively increases the low-voltage-activated calcium
      current of NG108-15 neuroblastoma x glioma cells.
AB  - The effect of bovine serum albumin (BSA) on the neuronal Ca2+ current (ICa) has
      been studied in NG108-15 cells. BSA selectively increased the low-voltage
      activated (l-v-a), transient ICa but did not affect the high-voltage-activated (h
      v-a) ICa. The increase of l-v-a ICa was partly due to a small shift of its
      activation curve to more negative values of membrane potential and partly to an
      increase of the maximal activatable current. Fatty-acid-free (FA-free) BSA was
      about equally effective as ordinary BSA; the smallest effective concentration of
      FA-free BSA was between 0.01 and 0.1 mg/ml.

PMID- 7820600
TI  - Conditional immortalization of neuronal cells from postmitotic cultures and adult
      CNS.
AB  - To determine whether postmitotic neurons can be immortalized by oncogenic
      transduction, we used two approaches involving conditional expression of a
      temperature-sensitive SV40 large T antigen (Tts). Initially, Tts was introduced
      into E17 rat embryonal hippocampal cells that were then cultured at the non
      permissive temperature to enrich for postmitotic pyramidal neurons, and
      subsequently cloned at the permissive temperature. One clonal line (HMR10-3)
      expressed neuron-specific proteins upon differentiation, was capable of
      generating action potentials, and formed synapses with primary rat neurons in co
      culture. Replating of these postmitotic cells at the permissive temperature
      resulted in reversible loss of neurofilament expression. Conditionally
      immortalized cell lines were also generated from the brain of an adult mouse
      carrying an inducible Tts transgene. These lines proliferated in a T antigen
      dependent manner and expressed neuron-specific proteins upon differentiation at
      the non-permissive temperature. These results suggest that postmitotic neurons
      can be induced to enter the cell cycle without losing their commitment to a
      neuronal lineage.

PMID- 7820601
TI  - Corticotrophin-releasing factor antagonist inhibits neuronal damage induced by
      focal cerebral ischaemia or activation of NMDA receptors in the rat brain.
AB  - This study investigated the involvement of corticotrophin-releasing factor (CRF)
      in acute neuronal damage induced by focal cerebral ischaemia or pharmacological
      activation of NMDA receptors in the rat brain. Intracerebroventricular injection
      of a CRF receptor antagonist (alpha-helical CRF9-41), markedly inhibited
      ischaemic (61%) and excitotoxic (41%) brain damage. Peripheral injection of a
      glucocorticoid antagonist (RU38486) did not affect ischaemic damage. Ischaemic
      and excitotoxic damage caused increased hypothalamic concentrations of CRF. These
      data indicate that CRF mediates ischaemic and excitotoxic neuronal damage in the
      rat, but that this effect is not dependent on glucocorticoids.

PMID- 7820602
TI  - 2-Mercaptoethanol-independent survival of fetal mouse brain neurons cultured in a
      medium of human serum.
AB  - In primary cultures of fetal mouse brain neurons, medium supplemented with fetal
      calf serum required 2-mercaptoethanol to support the survival and maturation of
      neurons, while medium containing human serum did not require the drug. These
      findings suggest that human serum is more active than fetal calf serum in
      reducing oxidative stress of neurons.

PMID- 7820603
TI  - Reduction of GABAA and GABAB receptor densities in the cerebellar cortex from 3
      acetylpyridine-induced ataxic rats.
AB  - We measured GABAA and GABAB receptor densities in the cerebellar cortex from 3
      acetylpyridine-induced ataxic rats using receptor autoradiography. GABAA and
      GABAB receptor densities were significantly reduced both in the molecular layer
      and the granule cell layer. Reduction of GABA receptor densities may be induced
      by loss of GABA receptors on the degenerated climbing fibers or by secondary or
      compensatory changes of neuronal activities in the cerebellum.

PMID- 7820604
TI  - Phosphorylation in vitro of glial fibrillary acidic protein is increased in rat
      hippocampus by administration of 2,5-hexanedione.
AB  - Rats were treated with 2,5-hexanedione (2,5-HD) daily for 30 days. Hippocampal
      microslices were then incubated with [32P]phosphate and the in vitro rate of
      phosphorylation and the immuno-content of glial acidic fibrillary protein (GFAP)
      were measured. Exposure to 2,5-HD decreased by 25% the immuno-content of GFAP and
      increased by 35% its rate of phosphorylation, resulting in an increase of 88% in
      the ratio phosphorylation rate/immuno-content for this protein.

PMID- 7820605
TI  - Blockade of transmission at NMDA receptors facilitates the electrical and
      synthetic activity of ascending serotoninergic neurones.
AB  - This study examined the influence of N-methyl-D-aspartate (NMDA) receptors upon
      the activity of serotoninergic neurones projecting from the rat dorsal raphe
      nucleus (DRN) to the striatum of rats. The channel blocker (+)-MK 801 (0.04-0.63
      mg/kg, s.c.) augmented striatal accumulation of the serotonin (5-HT) precursor, 5
      hydroxytryptophan (5-HTP), in rats treated with the inhibitor of decarboxylase,
      NSD 1015: the maximal effect of (+)-MK 801 was 164% relative to vehicle values (=
      100%). In analogy, (+)-MK 801 (0.01-0.5 mg/kg, i.v.) increased the firing rate of
      DRN neurones with a maximal effect of 204%. This action was stereospecific in
      that (-)-MK 801, which shows lower affinity at NMDA receptors, enhanced firing
      only at higher doses. The selective, competitive antagonist at the NMDA
      recognition site, CPP (0.5-8.0 mg/kg, i.v.), also facilitated the firing rate of
      DRN neurones, though with a maximal effect (137%) less than that of (+)-MK 801.
      Further, CPP (40.0 mg/kg, s.c.) did not significantly modify striatal 5-HT
      synthesis. While NMDA did not significantly modify DRN firing alone, it abolished
      the facilitatory action of CPP, consistent with a competitive interaction at the
      NMDA recognition site. In conclusion, blockade of NMDA receptors specifically
      facilitates the activity of ascending serotoninergic neurones.

PMID- 7820606
TI  - Calcium-dependent hyperexcitability of hippocampal CA1 pyramidal cells in an in
      vitro slice after ethanol withdrawal of the rat.
AB  - The physiological profiles contributing to hyperexcitability of hippocampal CA1
      neurons following ethanol withdrawal (EW) were examined in an in vitro slice
      preparation obtained from EW rats. Sixty-two percent of CA1 neurons in slices
      from EW rats exhibited intrinsic burst property which was rarely observed in
      those from control animals. The mean duration of plateau component of calcium
      (Ca) spikes was significantly increased after EW. The burst response evoked by
      either synaptic or direct stimulation in hippocampal CA1 neurons from EW rats was
      markedly depressed by high Mg solution but not by flunarizine. Furthermore, 6
      cyano-7-nitroquinoxaline-2,3-dione, a non-NMDA receptor antagonist, markedly
      depressed the synaptically evoked burst response, while [(+/-)-2
      carboxypiperazine-4-yl-]-propyl-1-phosphonic acid, a selective N-methyl-D
      aspartate (NMDA) receptor antagonist, slightly delayed the onset of the response.
      The results indicate that an increase in the number of bursting hippocampal CA1
      neurons associated with an augmentation of the plateau component of Ca spike
      contributes to the genesis of hyperexcitability in EW rats. Furthermore, non-NMDA
      receptor-mediated EPSP is mainly responsible for a synaptic induction of the
      burst response. These results are consistent with the involvement of high
      threshold Ca channels in EW hyperexcitability.

PMID- 7820607
TI  - Systemic administration of CCK-8S, but not CCK-4, enhances dopamine turnover in
      the posterior nucleus accumbens: a microdialysis study in freely moving rats.
AB  - The present study was carried out to examine the effects of peripheral
      administration of sulfatedcholecystokinin octapeptide (CCK-8S) on dopamine (DA)
      turnover in the posterior nucleus accumbens (PNAc) and the caudate-putamen (CP)
      in awake rats. Microdialysis was used to quantify the extracellular
      concentrations of DA and its two metabolites, 3,4-dihydroxyphenylacetic acid
      (DOPAC) and homovanillic acid (HVA). Intraperitoneal injections of CCK-8S (0.3
      mg/kg b.wt.) caused a significant increase in DOPAC and HVA concentrations in the
      PNAc, but did not affect the DA level. Such increases in the metabolite contents
      were not found in the CP. Similar injections of vehicle (1% NaHCO3 solution, 1
      ml/kg b.wt.) did not have an effect in either brain region. In an attempt to
      determine the type of receptor involved in the CCK-8S-induced changes, CCK
      tetrapeptide (CCK-4, 0.3 mg/kg b.wt.) known to have high affinity for CCKB
      subtype or vehicle (10% DMSO-saline, 1 ml/kg b.wt.) was administered
      intraperitoneally. Neither CCK-4 nor vehicle caused significant changes in any of
      extracellular DA, DOPAC and HVA contents in the PNAc. These results suggest that
      peripherally administered CCK-8S has stimulatory effects on the dopaminergic
      system in the PNAc, and raise the possibility that the effect appears to be
      mediated via CCKA receptors.

PMID- 7820609
TI  - Axonal transport of manganese and its relevance to selective neurotoxicity in the
      rat basal ganglia.
AB  - The present study provides evidence for anterograde axonal transport of manganese
      (Mn) in the basal ganglia. Microinjections of 54Mn into rat substantia nigra or
      striatum revealed region-specific accumulation and retention of the isotope in
      globus pallidus, striatum, thalamus and substantia nigra for up to at least 48 or
      72 h respectively. Within 4 h after intrastriatal injection of 54Mn,
      radioactivity accumulated in the substantia nigra, suggesting axonal transport of
      the metal. Subsequent studies using bilateral 54Mn injections into striatum or
      substantia nigra and unilateral colchicine injections into or transection of the
      medial forebrain bundle confirmed axonal transport of Mn through these fibres.
      Selective destruction of the striatonigral or nigrostriatal pathways using
      quinolinic acid or 6-hydroxydopamine 2 weeks before injection of the isotope,
      revealed uptake of 54Mn by cell bodies of both gamma-aminobutyric acidergic
      striatal and dopaminergic nigral neurons and subsequent anterograde transport
      through striatonigral or nigrostriatal fibres. In addition, the quinolinic acid
      lesioned striatum retained three times more radioactivity than the intact
      striatum. In conclusion, the present data suggest that both glial cells and
      striatonigral and nigrostriatal neurons are potential targets for Mn toxicity.
      These results and the selective neurotoxicity of Mn are discussed with respect to
      the iron transport protein transferrin, transferrin receptors, the iron storage
      protein ferritin, and mitochondrial dysfunction.

PMID- 7820610
TI  - Cutaneous hyperalgesia induced by peripheral injection of interleukin-1 beta in
      the rat.
AB  - The contribution of the activity of afferent fiber filaments to pain and
      hyperalgesia after administration of a plantar injection of interleukin-1 beta
      (IL-1 beta) to the hind-paw skin was investigated by recording action potentials
      of the rat dorsal root in response to mechanical and thermal stimuli. Touch
      stimuli were delivered by stroking with a cotton-tipped applicator and thermal
      stimulation was applied by cooling or heating of the skin. After the
      administration of IL-1 beta (100 pg-1 microgram), responses to touch, cold, and
      heat stimulation increased to 143%, 200%, and 392%, respectively, of control
      values on average. IL-1 beta induced transient spontaneous discharge in 50% of
      experiments. The effects of IL-1 beta were apparent within 1 min. To examine
      responses to pressure stimulation, an area of 1 mm2 of the hind-paw skin was
      pressed by a mechanical stimulator. IL-1 beta (0.1 pg-200 ng) decreased the
      threshold value to 58% of the control pressure required for firing. IL-1 beta
      also increased responses to various levels of pressure (range: 1-20 g/mm2). These
      data suggest that IL-1 beta may play an important role in cutaneous hyperalgesia
      by activating polymodal receptors to mechanical and thermal stimulation.

PMID- 7820608
TI  - Effects of steroidal and non steroidal aromatase inhibitors on sexual behavior
      and aromatase-immunoreactive cells and fibers in the quail brain.
AB  - Castrated quail were treated with Silastic implants filled with testosterone (T)
      in association with injections of the aromatase inhibitors, R76713 (racemic
      vorozole; 1 mg/kg twice a day) or 4-hydroxyandrostenedione (OHA; 5 mg/bird twice
      a day). Control birds received no treatment (CX group) or were implanted with T
      capsules only (CX + T group). Both R76713 and OHA strongly inhibited the T
      activated male copulatory behavior. This inhibition had the same magnitude in
      both groups. The growth of the cloacal gland, a strictly androgen-dependent
      process was not affected by these compounds. The treatments significantly
      affected the number of aromatase-immunoreactive (ARO-ir) cells in each of the six
      brain areas that were studied: the anterior and posterior parts of the sexually
      dimorphic medial preoptic nucleus (POM), the septal region, the bed nucleus of
      the stria terminalis (BNST) and the anterior and posterior parts of the tuber.
      This number was significantly increased in all areas by T. In agreement with our
      previous study, R76713 significantly inhibited this effect of T in the tuberal
      hypothalamus but not in the anterior POM nor in the BNST. By contrast the effect
      of T on the number of ARO-ir cells was completely blocked by OHA in all brain
      nuclei. The two inhibitors had statistically different effects in all brain
      regions. Like in a previous study, R76713 increased the intensity of the staining
      of all ARO-ir cells. This effect took several days to develop suggesting a
      progressive build-up of the enzyme concentration. This was also suggested by the
      fact that a rebound in aromatase activity was observed 16 to 24 h after a single
      injection of R76713. The increased immunoreactivity was not observed in OHA
      treated birds. The denser immunoreactivity in R76713-treated birds and the better
      tissue preservation due to the aldehyde fixative that had been used provided here
      a clearer picture of the cellular and subcellular localization of ARO-ir
      material. This allowed to identify new groups of immunoreactive cells, namely in
      the nucleus accumbens, in the area of the paleostriatum ventrale, in the nucleus
      taeniae, in the medial and caudal hypothalamus and in the medial part of the
      mesencephalon and of the pons. Most of the immunoreactive material was located in
      perikarya but some of these cells were also surrounded by dense networks of ARO
      ir fibers often associated with immunopositive punctate structures.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7820611
TI  - Effects of iboga alkaloids on morphine and cocaine self-administration in rats:
      relationship to tremorigenic effects and to effects on dopamine release in
      nucleus accumbens and striatum.
AB  - Ibogaine, a naturally occurring alkaloid, has been claimed to be effective in
      treating addiction to opioid and stimulant drugs and has been reported to
      decrease morphine and cocaine self-administration in rats. The present study
      sought to determine if other iboga alkaloids, as well as the chemically related
      harmala alkaloid harmaline, would also reduce the intravenous self-administration
      of morphine and cocaine in rats. Because both ibogaine and harmaline induce
      tremors, an effect that may be causally related to neurotoxicity in the
      cerebellar vermis, the temorigenic activities of the other iboga alkaloids were
      assessed. Lastly, in view of the involvement of the dopaminergic mesolimbic
      system in the actions of drugs of abuse, the effects of some of the iboga
      alkaloids on extracellular levels of dopamine and its metabolites in the nucleus
      accumbens and striatum were determined. All of the tested alkaloids (i.e.,
      ibogaine, tabernanthine, R- and S-coronaridine, R- and S-ibogamine,
      desethylcoronaridine, and harmaline) dose-dependently (2.5-80 mg/kg) decreased
      morphine and cocaine intake in the hour after treatment; decreases in morphine
      and cocaine intake intake were also apparent the day after administration of some
      but not all of these alkaloids (i.e., ibogaine, tabernanthine,
      desethylcoronaridine, and the R-isomers of coronaridine and ibogamine). In some
      rats, there were persistent decreases in morphine or cocaine intake for several
      days after a single injection or after two or three weekly injections of one or
      another of these alkaloids; R-ibogamine produced such effects more consistently
      than any of the other alkaloids.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7820612
TI  - Effects of corticosterone on CRH mRNA and content in the bed nucleus of the stria
      terminalis; comparison with the effects in the central nucleus of the amygdala
      and the paraventricular nucleus of the hypothalamus.
AB  - We previously reported that corticosterone (CORT) increased corticotropin
      releasing hormone (CRH) mRNA in the central nucleus of the amygdala (CEA), while
      reducing it in the paraventricular nucleus (PVN) of the hypothalamus by using in
      situ hybridization histochemistry. The bed nucleus of the stria terminalis (BNST)
      is closely related to the amygdala, and it is also a source of extrahypothalamic
      CRH; therefore, we examined CRH mRNA changes in the BNST following systemic
      treatment with CORT in adrenally-intact rats. Effects of adrenalectomy on CRH
      mRNA in the BNST, PVN and CEA were also examined. In addition, CRH content in
      these nuclei and in the median eminence (ME) were determined by micropunch
      dissection technique combined with CRH radioimmunoassay in CORT pellet implanted
      rats. Subcutaneous injections of high CORT (5 mg/day, over 14 days) increased CRH
      mRNA in the dorsal part of the lateral BNST (BSTLD) at 2, 4 and 8 days, although
      the low dose of CORT (1 mg/kg/day) had no significant effects. By contrast, in
      the ventral part of the BNST (BSTV) neither the high nor low dose of CORT altered
      CRH mRNA levels. In a second experiment, a slowly-releasing CORT pellet (200 mg,
      60-day release) produced an elevation of CRH mRNA at both 1 and 2 weeks or at 1
      week in the BSTLD or in the BSTV, respectively. These results show that
      glucocorticoids can facilitate CRH mRNA expression in the BSTLD in the same
      manner as seen in the CEA, and that CRH mRNA in the BSTLD can respond to CORT
      more than in the BSTV. In a third experiment, bilateral adrenalectomy, however,
      did not affect CRH mRNA in the BNST although there was a modest decrease in the
      CEA and a robust increase in the PVN. Finally, in CORT pellet (200 mg, for 2
      weeks) implanted rats, CRH content in the ME significantly decreased and modestly
      increased in the CEA compared with control rats, whereas it did not change in the
      PVN and BNST. Taken together, these results suggest that (1) CRH in the BNST and
      the CEA may share some common functions in neuroendocrine and behavioral changes,
      but that (2) mechanisms of CRH synthesis or its releasing sites may be different
      in the BNST and CEA.

PMID- 7820613
TI  - Microzonal decreases in the immunostaining for non-NMDA ionotropic excitatory
      amino acid receptor subunits GluR 2/3 and GluR 5/6/7 in the human epileptogenic
      neocortex.
AB  - Potential alterations in glutamate-utilizing excitatory circuits in resected
      human epileptogenic frontal and temporal neocortex were investigated by using
      immunocytochemical methods to visualize receptor subunits which comprise the
      AMPA/kainate (GluR2/3) and kainate (GluR5/6/7) receptor subtypes. Examination of
      the patterns of immunostaining in regions of neocortex that were identified as
      spiking and non-spiking based on intraoperative electrocorticography revealed
      dramatic, microzonal decreases in immunoreactivity for the receptor subunits
      examined. The patches of decreased immunostaining for GluR2/3 and for GluR5/6/7
      were often coincident with respect to each other. However, such abnormal regions
      were not necessarily correlated with any particular electrocorticographically
      defined regions nor any overtly abnormal cytoarchitectural features in adjacent
      Nissl-stained sections. Moreover in many but not all cases, the focal regions of
      decreased receptor subunit immunoreactivity coincided with small patches of
      decreased parvalbumin immunoreactivity a calcium-binding protein which labels a
      subpopulation of powerful inhibitory GABAergic interneurons. These results
      indicate that in the human epileptogenic neocortex there may be alterations in
      particular excitatory and/or inhibitory synaptic systems at small, multiple
      neocortical foci, and that these alterations are found mostly in the same
      regions. We suggest that these alterations may contribute to the initiation
      and/or propagation of seizure activity.

PMID- 7820614
TI  - Cholecystokinin octapeptide (CCK-8) antagonizes morphine analgesia in nucleus
      accumbens of the rat via the CCK-B receptor.
AB  - The analgesic effect of systemic morphine (4 mg/kg, s.c.) was antagonized in a
      dose-dependent manner by cholecystokinin octapeptide (CCK-8) (0.1-0.5 ng)
      administered bilaterally to the nucleus accumbens of the rat. This effect of CCK
      8 could be reversed by devazepide, a CCK-A receptor antagonist, at 50 ng and 200
      ng and by L-365,260, a CCK-B receptor antagonist, at 5 ng administered
      bilaterally to the nucleus accumbens. A marked potentiation of morphine analgesia
      was achieved by intra-nucleus accumbens injection of 200 ng devazepide or 5 ng L
      365,260. Since the effect of L-365,260 in antagonizing the anti-opioid effect of
      CCK-8 in the nucleus accumbens is 40 times more potent than devazepide, it is
      suggested that the anti-opioid effect of CCK-8 is mediated by CCK-B receptors. In
      conclusion, nucleus accumbens is a strategic site where CCK-8 exerts an anti
      opioid activity, most probably via the CCK-B receptors.

PMID- 7820615
TI  - Working memory performance and cholinergic effects in the ventral tegmental area
      and substantia nigra.
AB  - The nicotinic antagonist mecamylamine has been found to impair working memory
      performance in the radial-arm maze (RAM) after s.c. or i.c.v. administration.
      Mecamylamine has important interactions with dopaminergic (DA) systems.
      Mecamylamine-induced memory deficits in the RAM are potentiated by the D2
      antagonist raclopride and reversed by the D2 agonist quinpirole. The nicotinic
      agonist nicotine has been found to improve working memory performance in the RAM
      after s.c. or i.c.v. administration. Nicotine-induced memory improvement in the
      RAM is potentiated by the D2 agonist quinpirole. The midbrain DA nuclei, the
      substantia nigra (SN) and the ventral tegmental area (VTA) have relatively dense
      concentrations of nicotinic receptors which may be critical sites of action for
      mecamylamine and nicotine. In the current study, the effects of mecamylamine (1,
      3.3 and 10 micrograms/side) infusions into the SN (n = 12) and VTA (n = 13) on
      working memory in the radial-arm maze were examined in adult female Sprague
      Dawley rats. The 10-micrograms/side dose of mecamylamine significantly impaired
      radial-arm maze working memory performance when infused into either the SN or
      VTA. No significant effects of mecamylamine on response latency were seen. The
      nicotinic agonists cytisine (0.1, 0.33 and 1.0 microgram/side) and nicotine (0.3,
      1.0 and 3.3 micrograms/side) were administered in a counterbalanced order. The
      high dose of cytisine (1 microgram/side) nearly caused a significant deficit in
      choice accuracy. Nicotine slightly depressed choice accuracy but not
      significantly in this study. The interaction of nicotine and mecamylamine was
      then studied. A dose of 1.0 microgram/side of nicotine caused a significant
      decrease in choice accuracy. Interestingly, this was significantly reversed by a
      3.3-micrograms/side dose of mecamylamine.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7820616
TI  - Vasotocinergic innervation of sexually dimorphic medial preoptic nucleus of the
      male Japanese quail: influence of testosterone.
AB  - The distribution of vasotocin (VT)-immunoreactive (IR) fibers was described in
      the preoptic and septal regions of the male quail brain. The density of VT-IR
      fibers was measured in the sexually dimorphic preoptic nucleus (POM) and lateral
      septum (SL) of adult male quail (Coturnix japonica) by means of quantitative
      image analysis. Experimental manipulations of the hormonal environment in the
      peripubertal period influenced this distribution. In both regions, the VT
      immunoreactivity was reduced or absent when males were castrated. The
      immunoreactivity was restored to its original level in castrated males by
      Silastic implants of testosterone. These changes were anatomically specific as
      evidenced by the fact that the density of VT fibers did not vary in the
      hypothalamo-neurohypohysial tract as a function of the endocrine condition of the
      subjects. No change was also observed in the number of VT-IR cells in the
      periventricular region close to the POM. Previously published data show that VT
      or its mammalian homolog, vasopressin are implicated in the control of a wide
      range of instinctive behaviors. The steroid-dependent VT afferents to the POM, a
      key area controlling male copulatory behavior in quail could therefore be
      involved in the control of the sexual behavior in this species. The outputs of
      the POM which contains steroid-receptors could therefore be modulated by steroids
      in two different ways: directly through the steroid receptors it contains and
      indirectly through its steroid-sensitive peptidergic afferents.

PMID- 7820617
TI  - Nicotinic and muscarinic acetylcholine responses in the embryo chick ciliary
      ganglion cells.
AB  - Nicotinic and muscarinic acetylcholine (ACh) responses were investigated in
      acutely dissociated chick ciliary ganglion neurons using the nystatin perforated
      patch clamp technique. ACh-induced a rapid transient inward current in 100% of
      the neurons at a holding potential of -60 mV. This rapid inward current was
      mimicked by nicotine but not by muscarine. The reversal potential of the rapid
      inward current was +10.5 mV and the current was inhibited by d-tubocurarine and
      hexamethonium in a dose-dependent manner. In 57.6% of neurons, a slow inward
      current was also induced by ACh at a holding potential of -20 mV. This slow
      inward current was mimicked by muscarine but not by nicotine. The slow inward
      current became smaller at a hyperpolarized potential but not reversed, being
      consistent with the fact that this current was elicited by the inhibition of M
      current. p-Fluorohexa-hydrosiladifenidol (P-F-HHSiD) strongly inhibited the slow
      inward current, suggesting that the current was elicited by the activation of M3
      receptors.

PMID- 7820618
TI  - Selective alterations in macronutrient intake of food-deprived or glucoprivic
      rats by centrally-administered opioid receptor subtype antagonists in rats.
AB  - Two hypotheses have attempted to account for the abilities of opioid agonists and
      antagonists to respectively stimulate and inhibit food intake in rats. The first
      suggests that the opioid system selectively modulates fat intake, while the
      second suggest that the opioid system selectively alters intake of that
      macronutrient which the animal prefers. The present study evaluated these two
      hypotheses by examining total intake and individual macronutrient intake in
      either food-deprived (24 h) rats or rats made glucoprivic with 2-deoxy-D-glucose
      (2DG, 200 mg/kg, i.p.) following either vehicle treatment, systemic
      administration of naltrexone or intracerebroventricular administration of either
      naltrexone, the mu opioid antagonist, beta-funaltrexamine (B-FNA), the mu1 opioid
      antagonist, naloxonazine, the kappa opioid antagonist, nor-binaltorphamine (Nor
      BNI), the delta opioid antagonist, naltrindole or the delta1 opioid antagonist,
      DALCE. Systemic administration of naltrexone (0.5-5 mg/kg significantly reduced
      carbohydrate, fat and total intake in deprived rats, and carbohydrate, fat,
      protein and total intake in glucoprivic rats. Central administration of
      naltrexone (5-50 micrograms) significantly reduced fat and total intake in both
      deprived and glucoprivic rats. B-FNA (5-20 micrograms) significantly reduced
      carbohydrate, fat and total intake in both deprived and glucoprivic rats
      Naloxonazine (10-100 micrograms) significantly reduced carbohydrate, fat and
      total intake in deprived rats, but failed to alter 2DC intake. Nor-BNI (5-20
      micrograms) significantly reduced fat and total intake in glucoprivic rats, but
      failed to alter deprivation intake. Neither naltrindole (20 micrograms) nor DALCE
      (40 micrograms altered intake in deprived or glucoprivic rats. Carbohydrate or
      fat preference in deprived rats significantly increased the amount of explained
      variance in the inhibitory actions of central naltrexone, B-FNA and naloxonazine
      upon deprivation-induced intake. Carbohydrate or fat preference in glucoprivic
      rats significantly increased the amount of explained variance in the inhibitory
      action of systemic and central naltrexone, B-FNA, naloxonazine and Nor-BN upon 2
      DG hyperphagia. These data are discussed in terms of the contentions that opioids
      either selectively alter fat intake pe se or selectively alter the preferred
      macronutrient.

PMID- 7820619
TI  - Bromocriptine protects mice against 6-hydroxydopamine and scavenges hydroxyl free
      radicals in vitro.
AB  - Pretreatment with bromocriptine (5 mg/kg, i.p., 7 days) completely protected
      against the decrease in mouse striatal dopamine and its metabolites induced by
      intraventricular injection of 6-hydroxydopamine after intraperitoneal
      administration of desipramine, but similar pretreatment with L-DOPA/carbidopa
      (75/7.5 mg/kg, i.p., 7 days) showed only partial protective effect. Furthermore,
      in an in vitro system that generated.OH from FeSO4-H2O2, bromocriptine dose
      dependently reduced the number of .OH radicals. These findings indicate that
      bromocriptine has a neuroprotective effect against neurotoxins such as 6
      hydroxydopamine, probably due, in part, to its hydroxyl radical scavenging
      activity and inhibiting effect on dopamine turnover rate. This suggests that
      early introduction of bromocriptine in the therapy of Parkinson's disease may be
      superior to treatment with L-DOPA alone.

PMID- 7820620
TI  - Modulation of temporalis muscle exteroceptive suppression by limb stimuli in
      normal man.
AB  - The effects of noxious and non-noxious limb stimulations on the second
      exteroceptive suppression of voluntary temporalis muscle activity (ES2) were
      studied in healthy human volunteers. Duration of temporalis ES2 was measured on
      averaged rectified responses obtained after stimulating the labial commissure at
      an intensity of 25 mA. Single peripheral electrical stimuli applied over nerve
      trunks or over the skin before the labial stimulus decreased ES2 duration. This
      effect was most pronounced after cutaneous stimuli, especially of the index
      finger, and it was not observed when the conditioning stimulus was a 10 second,
      high frequency train. For stimulation at the index finger, temporalis ES2
      inhibition progressively increased with intensity from 10 mA to 40 mA; it was
      maximal for an interstimulus interval between 50 and 140 ms. After naloxone (0.4
      mg or 4 mg, i.v.) there was a partial reversal of the index-induced ES2
      depression, but this effect was not significant. Immersion of one hand in water
      heated at 47 degrees C produced a short-lasting ES2 reduction. These results are
      comparable, though not similar, to the inhibition of the digastric reflex (or jaw
      opening reflex) observed in animals after limb stimuli and to the depression of
      the spinal flexion reflex reported in man after heterotopic peripheral stimuli.
      Although peripheral stimuli were able by themselves to suppress temporalis EMG
      activity in some subjects, it is likely that they reduce labial-induced ES2 via
      activation of brainstem structures, such as periaqueductal gray matter or raphe
      magnus nucleus, which are thought to inhibit the medullary inhibitory
      interneurons mediating ES2.

PMID- 7820621
TI  - Neuroanatomical organization of GnRH neuronal systems in the lizard (Podarcis s.
      sicula) brain during development.
AB  - The ontogenesis of the GnRH neuronal systems was studied in the brain of the
      lizard, Podarcis s. sicula, by immunohistochemistry. The first GnRH neurons were
      seen in the mesencephalon on the 45th day of incubation. One week later GnRH-ir
      neurons appeared in the infundibulum as well. These neurons never appeared to be
      contiguous with midbrain GnRH neurons. Thus, the adult pattern of distribution of
      GnRH neurons was reached before hatching, which occurred on the 66th day of
      incubation at a temperature of 28 +/- 2 degrees C. Although mesencephalic and
      infundibular GnRH neurons and their fiber projections appeared to be distributed
      in anatomically distinct brain areas, both systems showed a positive reaction to
      chicken-I GnRH (cGnRH-I), chicken-II GnRH (cGnRH-II) and salmon GnRH (sGnRH).
      From the time of hatching, GnRH-ir fibers in the mesencephalon appeared to be
      reaching the optic tectum, tegmentum, cerebellum and rostral dorsal
      rhombencephalon, whereas GnRH fibers in the infundibulum were projecting to the
      caudal basal telencephalon, median eminence and rostral basal rhombencephalon. In
      60-day-old juvenile lizards, the central area of telencephalon contained neurons
      reacting only with anti-cGnRH-I and anti-sGnRH. Such neurons were absent in the
      adult. Neither GnRH cells nor fibers were observed in the nasal area, terminal
      nerve and olfactory bulbs at any stage of development and in the adult. We
      hypothesize that the two GnRH neuronal systems have separate embryonic origins.

PMID- 7820622
TI  - The effects of long-term corticosterone administration on hippocampal morphology
      and cognitive performance of middle-aged rats.
AB  - The main objective of this research was to study the relationship between
      glucocorticoids, aging and the deterioration of cognitive functions. Towards this
      end, an attempt was made to develop an animal model which will enable the
      investigation of such interactions, using subcutaneously implanted sustained
      release corticosterone pellets. The goal was to achieve moderately high
      concentrations of corticosterone in plasma, comparable to the peak basal levels
      or to those found under mild stress. Middle-aged (12 months old) Fischer-344
      rats, used in this study, were divided before the prolonged hormonal treatment
      into cognitively 'impaired' and 'non-impaired' groups using the Morris water
      maze. The cognitive impairment, which was induced by the long-term corticosterone
      administration, was exhibited during acquisition of the 8-arm radial maze only in
      the 'non-impaired' group. Behavioral scores for drug-treated 'impaired' rats were
      not statistically different from those of the placebo-treated 'impaired' group.
      The morphological deterioration in hippocampal areas of the brain was quantified
      and revealed high correlation with the behavioral data. This animal model may
      become extremely useful in testing projected prophylactic therapy against the
      brain damage and cognitive deficits induced by the high corticosteroid-aging
      combination.

PMID- 7820623
TI  - The role of stretch reflex threshold regulation in normal and impaired motor
      control.
AB  - Some hypotheses suggest that stretch reflex threshold regulation may be an
      essential element of motor control. Disturbances in this mechanism may lead to
      motor dysfunction. We investigated this possibility by comparing stretch reflex
      threshold regulation in 11 spastic hemiparetic and 6 normal subjects. Subjects
      sat with their arms fully supported in a forearm and hand mold attached to a
      manipulandum mounted on and controlled by a torque motor. They remained
      completely passive while their elbow was extended from 30 degrees flexion through
      an arc of 100 degrees. Displacement and velocity of the forearm were measured as
      well as EMG signals from 2 elbow flexors and 2 elbow extensors, when the elbow
      flexors were stretched at each of 7 velocities. Velocities ranged from 8 to 160
      degrees/s for hemiparetic subjects and from 32 to 300 degrees/s for normal
      subjects. Phase diagrams (velocity versus angle) were plotted and the threshold
      angles (lambda) for muscle activation at each velocity of stretch were used to
      determine the static stretch reflex threshold (lambda) and the slope (mu) of the
      relationship between the lambda s and velocity. Our main findings were that
      static and dynamic stretch reflex thresholds were decreased in spastic
      hemiparetic compared to normal subjects and that the thresholds depended on
      velocity. The static threshold value correlated with the severity of clinically
      measured spasticity. In addition, the range of regulation of lambda was decreased
      in the patients compared to normal. This may explain some of the problems of
      force and position regulation as well as hypertonus (and weakness) common to
      these patients.

PMID- 7820624
TI  - Animals predisposed to develop amphetamine self-administration show higher
      susceptibility to develop contextual conditioning of both amphetamine-induced
      hyperlocomotion and sensitization.
AB  - It has been shown that rats, like humans, display individual differences in the
      propensity to develop psychostimulant self-administration. Animals showing the
      highest locomotor reactivity to novelty (HRs: High Responders) are more prone to
      develop amphetamine self-administration than rats having a low locomotor response
      to novelty (LRs: Low Responders). The present study was designed to ascertain
      whether individual differences are also present in the conditioning of drug
      effects, a process involved in the maintenance of addiction. After pairing the
      drug effect with a particular set of environmental cues, only HRs showed
      conditioned hyperlocomotion and environment-specific sensitization to the effect
      of amphetamine. Unconditioned sensitization was, however, observed in LRs but not
      in HRs. The environment-specific sensitization disappeared on extinction of the
      conditioned hyperlocomotion in HRs, indicating that conditioning facilitates the
      expression of sensitization. In contrast, an inhibitory influence of conditioning
      on sensitization emerged from the analysis of the same results over all the
      experimental groups, without taking individual differences into account. In
      conclusion, our results show that: (i) locomotor reactivity to novelty predicts
      both vulnerability to develop self-administration and contextual conditioning of
      drug effects, which suggests that the two phenomena are two related features and
      that conditioning plays an important role not only in the maintenance of drug
      intake but also in its development; (ii) conditioned and unconditioned
      sensitization can be developed separately in different individuals which suggests
      that they are independent phenomena; (iii) analysis of individual differences is
      relevant to pharmacological studies, especially with respect to drugs of abuse.

PMID- 7820625
TI  - Quantitative immunofluorescence data suggest a permanently enhanced GAD67/GAD65
      ratio in nerve endings in rat cerebral cortex damaged by early postnatal hypoxia
      ischemia: a comparison between two computer-assisted procedures for
      quantification of confocal laser scanning microscopic immunofluorescence images.
AB  - The aim of the present study was 2-fold: (1) to determine the ratio between the
      amount of GAD67 and GAD65 (two isoforms of the GABA synthetizing enzyme glutamic
      acid decarboxylase) in nerve endings in the mature rat cerebral cortex damaged by
      hypoxia-ischemia during early postnatal life; and (2) to compare two different
      computer-assisted procedures developed for quantitative analysis of
      immunofluorescence images obtained with a confocal laser scanning microscope
      (CLSM). One procedure was based on a program present in the standard Leica CLSM
      software packet for full-field analysis, the other on a specially written program
      for object-oriented analysis run on a Kontron IBAS-KAT image analysis system. To
      this end, rat pups were unilaterally exposed to hypoxic-ischemic conditions and,
      after a survival period of 6.5 months, sacrificed by perfusion fixation. After
      dissection of the brain and vibratome sectioning, three animals with substantial
      damage on one cortical side were selected. Sections of these animals were double
      stained with primary antibodies against GAD67 and GAD65 and fluorophore
      conjugated secondary antibodies and subsequently sampled with a CLSM. Analysis of
      the CLSM images with both computer-assisted procedures showed for all three
      animals a clear tendency to higher GAD67/GAD65 ratios in cortical GABAergic nerve
      endings on the hypoxia-damaged side than in matched areas on the contralateral
      side. This outcome led to the following conclusions. (1) The correspondence
      between the outcome of both analysis procedures indicates that both procedures
      are valid for quantification of immunofluorescence images of nerve endings
      obtained with a CLSM. (2) The outcome lends further support to our view that
      hypoxic-ischemic encephalopathy, sustained during early postnatal life, may
      result in an unstable cortical network generating abnormal synchronizations and
      oscillations which can be amplified and propagated as true epileptic discharges.
      In such a network both excitatory and inhibitory processes are tonically
      enhanced, the latter probably as a homeostatic reaction tending to keep abnormal
      excitation within physiological limits.

PMID- 7820626
TI  - Localization of barosensitive neurons in the caudal ventrolateral medulla which
      project to the rostral ventrolateral medulla.
AB  - A population of depressor neurons in the caudal ventrolateral medulla that
      project to the rostral ventrolateral medulla may mediate the baroreceptor reflex.
      The aim of the present study was to determine the anatomical distribution of the
      population of neurons in the caudal ventrolateral medulla that mediate the
      baroreceptor reflex. Injection of the retrogradely transported tracer, rhodamine
      labelled latex beads, into the pressor area of the rostral ventrolateral medulla
      of rats was used to identify neurons in the caudal ventrolateral medulla with
      projections to that area. Barosensitive neurons were identified by
      immunohistochemical detection of the protein Fos, a marker of neuronal
      activation, following infusion of the pressor agent phenylephrine (10
      micrograms/kg/min, i.v. for 2 h n = 5). Isotonic saline was infused into control
      animals (n = 4). Neurons in the caudal ventrolateral medulla with projections to
      the rostral ventrolateral medulla were located at all rostrocaudal levels
      examined between 1 mm caudal and 0.4 mm rostral of the obex. Compared to saline
      infused rats, phenylephrine infusion induced a significant increase in the
      proportion of those neurons that expressed Fos (14% vs. 1% P < 0.000.1). These
      barosensitive neurons were found mainly at the level of the obex, between the
      lateral reticular nucleus and the nucleus ambiguus. In conclusion, this study is
      the first to show the distribution of the population of barosensitive neurons in
      the caudal ventrolateral medulla that project to the pressor region of the
      rostroventrolateral medulla. The results suggest there is a subpopulation of
      depressor neurons, confined to a small region of the rostral part of the caudal
      ventrolateral medulla, that are likely to be the interneurons that mediate the
      baroreceptor-reflex response.

PMID- 7820627
TI  - Motor expression of kainic acid seizures is attenuated by dopamine depletion in
      mice.
AB  - We studied the effect of striatal dopamine depletion induced by 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP) in mice on kainic acid (KA) evoked seizures.
      MPTP, 36 mg/kgp i.p. for 3 days, caused an 80% drop of striatal dopamine. Animals
      pretreated with MPTP, plus controls treated with saline, were challenged with
      five different convulsant doses of KA (3, 6, 12, 18 and 36 mg/kg i.p.). The
      seizures were monitored by electrographic recording and behavioral observation.
      MPTP pretreatment greatly attenuated the severity of the convulsions and the
      mortality induced by KA. The effect was mostly evident at the intermediate and at
      the high doses of KA. Surprisingly, no differences between the MPTP and control
      groups were found on the intensity and time course of the electrical seizures.
      Increment doses of KA resulted in a more severe electrographic seizure pattern in
      both the saline and the MPTP pretreated groups. Our data suggest that the
      dopamine depletion induced by MPTP does not alter the genesis of KA induced
      seizures, but may alter the function of cerebral structures involved in the
      control of seizure motor expression.

PMID- 7820628
TI  - Characterisation of the DA-ergic system in the mediobasal hypothalamus: a new
      approach to simultaneously monitor the release of DA from the TIDA neurons and
      the PRL secretion from the adenohypophysis in awake rats.
AB  - The TIDA neurons, which constitute part of the arcuate nucleus-ME complex, play
      an important inhibitory role in the regulation of the PRL secretion from the
      adenohypophysis. To simultaneously study the release of DA from the TIDA neurons
      and the PRL secretion from the adenohypophysis in awake rats, a microdialysis
      probe was implanted into the MBH together with a permanent heartcannula in male
      rats. The extracellular levels of DA in the MBH as measured by microdialysis
      decreased to 25% of basal values after local infusion of TTX (1 mumol/l),
      indicating that the released DA was directly derived from neuronal activity.
      DOPAC levels were not affected. This local infusion of TTX into the MBH induced
      parallel to the immediate decrease in DA levels, a profound increase in PRL
      concentration in the blood (from 10 to 55 ng/PRL-RP-2/ml) directly after
      infusion. Thus, the area in which the dialysis probe was inserted indeed included
      the DA-ergic neurons that regulate the PRL secretion. Evidence for a functional
      re-uptake system in the MBH was obtained by local infusion of the re-uptake
      inhibitor nomifensine (5 mumol/l) which induced an increase in DA release to 350%
      of basal values, without affecting the DOPAC levels. In spite of this increase in
      DA levels, the PRL concentration in the blood was not affected. In pseudopregnant
      female rats, relatively high levels of extracellular DA in the MBH were obtained
      during the interphase during which the PRL levels are low, while lower DA levels
      were apparent during the phase the spontaneous nocturnal PRL surge normally
      appears. Taken together, the approach presented in this study, i.e. the
      simultaneous measurements of DA in the MBH and PRL in the blood, establishes an
      advanced method enabling studies on the DA-PRL interactions in awake animals.

PMID- 7820629
TI  - Differential expression of the neuroendocrine polypeptide 7B2 in hypothalami of
      Prader-(Labhart)-Willi syndrome patients.
AB  - Prader-(Labhart-)Willi syndrome (PWS) is characterized by infantile hypotonia,
      early childhood obesity, mental deficiency, short stature, small hands and feet
      and hypogonadism. In 70% of the cases this syndrome is associated with a defect
      of chromosome 15 at 15q11-q13, close to the location of the 7B2 gene (15q13-q14).
      The majority of the remaining PWS patients display maternal uniparental disomy on
      chromosome 15. Since the 7B2 gene products are expressed in neuroendocrine cells
      that are probably affected in PWS, e.g. by a pleiotrophic influence of the
      neighboring deletion, the presence of 7B2 was studied in the supraoptic and
      paraventricular nucleus of the hypothalamus of five subjects clinically diagnosed
      as PWS patients using five antibodies against various parts of the 7B2 precursor
      polypeptide. Three of the five PWS patients studied showed no reaction to the 7B2
      antibody MON-102, whereas all 30 control patients did. However, one of the three
      MON-102 non-reacting PWS patients reacted to other 7B2 antibodies. In conclusion,
      the vanishing of 7B2 gene products is not obligatory for PWS, possibly due to the
      variable genetic background of PWS patients. However, in most patients there is a
      clear modification of 7B2 expression, pointing to altered neuroendocrine
      functions.

PMID- 7820631
TI  - A paradoxical inhibitory effect of xanthines on hippocampal excitability in
      calcium-free media.
AB  - In calcium-free media, neurones in the rat hippocampal slice develop bursts of
      population potentials and lose their sensitivity to adenosine. The present paper
      reports the unexpected and paradoxical finding that the xanthines theophylline
      and cyclopentyltheophylline, the latter of which is selective for A1 purine
      receptors, depressed the excitability of hippocampal pyramidal neurones in
      calcium-free media. Chelating residual calcium with EGTA reduced excitability
      which was additive with the xanthine effect, while 100 microM calcium depressed
      the response to theophylline. The inhibition by xanthines was prevented by
      adenosine, which had no effect by itself, but was not reproduced or modified by
      adenosine deaminase. The xanthine effects were also prevented by baclofen and
      carbamazepine. A common feature of adenosine, baclofen and carbamazepine which
      may account for their antagonism of the xanthines is the blockade of calcium
      fluxes. It is proposed that in the presence of low external concentrations of
      calcium xanthines can reduce excitability by promoting the mobilisation and trans
      membrane movement of residual calcium in the medium or neuronal membranes.

PMID- 7820630
TI  - Calcium/calmodulin-dependent protein kinase II immunostaining is preserved in
      Alzheimer's disease hippocampal neurons.
AB  - Alterations in protein phosphorylation may be important in the pathogenesis of
      Alzheimer's disease and recent observations suggest that a subset of protein
      kinase pathways may be selectively altered. Calcium/calmodulin-dependent protein
      kinase II CaM kinase II) is the most abundant protein kinase in the brain and is
      believed to play an important role in the regulation of synaptic transmission,
      long-term potentiation and other forms of neuronal plasticity. We have now
      evaluated brains of individuals with Alzheimer's disease for changes in the
      distribution and density of immunoreactivity for the alpha subunit of CaM kinase
      II. CaM kinase II immunoreactivity was found in cytoarchitectural areas and
      neurons vulnerable to the formation of neurofibrillary angles and senile plaques.
      Over 80% of neurons bearing neurofibrillary tangles expressed CaM kinase II. Loss
      of CaM kinase II immunoreactivity was found in CA1, commensurate with neuronal
      loss in this area. Remaining CA1 neurons, however, had preserved CaM kinase II
      immunoreactivity. Preservation in the distribution and density of CaM kinase II
      immunoreactivity was observed in other hippocampal regions and in a multimodal
      association area, area 20. These results suggest CaM kinase II expression in the
      Alzheimer's disease brain is unaltered despite marked neuropathological changes.

PMID- 7820632
TI  - Measurement of dopa and immunolocalization of L-dopa-positive nerve fibers in rat
      dental pulp.
AB  - dopa, norepinephrine, and traces of dopamine, epinephrine were present in in rat
      dental pulp. L-dopa was localized in nerve fibers in dental pulp. The results
      suggest that L-dopa-positive nerve fibers are present in dental pulp as well as
      classical adrenergic fibers.

PMID- 7820633
TI  - Parvalbumin-immunopositive neurons in rat globus pallidus: a light and electron
      microscopic study.
AB  - To add to our understanding of the anatomical organization of the globus pallidus
      (GP) of the rat, a light and electron microscopic analysis of parvalbumin (PV, a
      Ca-binding protein) immunoreactive neurons in the GP was performed. Light
      microscopic analysis revealed that the GP contains PV-positive and PV-negative
      neurons. Approximately two-thirds of the GP neurons were PV-positive. The somata
      of PV-positive neurons were, on average, larger than PV-negative ones. The
      proximal dendrites of PV-positive neurons were smooth and often lay parallel to
      the border between the GP and the neostriatum. Distal dendrites of PV-positive
      neurons were varicose. Thin PV-positive fibers with large boutons (with average
      diameter of 1.7 microns) were observed in the neuropil of the GP. Some PV
      positive boutons formed basket-like aggregates surrounding the somata of PV
      positive or negative neurons. Electron microscopic observations revealed that PV
      positive neurons were often large and contained deeply indented nuclei and a
      large volume of cytoplasm. PV-negative neurons had smaller somata that were
      occupied by deeply indented nuclei and a small volume of cytoplasm. Both PV
      positive and negative neurons were contacted by synaptic boutons identical to the
      known striato-pallidal, subthalamo-pallidal, and local collateral boutons. The PV
      positive boutons contained small round or elongated vesicles and often more than
      one mitochondrion. Most of the boutons (i.e. 86%) formed symmetric synapses with
      somata and large dendrites and, the other (14%) formed asymmetric synapses with
      small dendrites. The study indicated that GP projection neurons can be divided
      into two subgroups according to their PV-immunoreactivity. PV-positive and
      negative neurons received similar extrinsic synaptic inputs and both types of
      neurons were connected through their local collateral axons. It is conceivable
      that the physiology of PV-positive and negative neurons might be different
      because of a difference in the Ca-buffering mechanisms in these neurons.

PMID- 7820634
TI  - Central opioid receptor subtype mediation of isoproterenol-induced drinking in
      rats.
AB  - Opioid receptor subtype antagonists differentially alter different types of water
      intake such that mu2 receptors modulate deprivation-induced water intake, kappa
      receptors modulate hypertonic saline-induced water intake, and mu2, delta1 and
      kappa receptors modulate water intake following Angiotensin II (ANG II). Water
      intake stimulated by peripheral administration of the beta-adrenergic agonist,
      isoproterenol is attenuated by naloxone and is thought to be mediated by release
      of renin and production of ANG II. The present study examined whether systemic
      and i.c.v. administration of general opioid antagonists and central
      administration of specific opioid receptor subtype antagonists would selectively
      alter water intake following isoproterenol in rats. Both systemic (1 mg/kg s.c.)
      and central (1-20 micrograms) naltrexone reduced water intake induced by
      isoproterenol (25 micrograms/kg s.c.) over a 2-h period. The mu receptor
      antagonist, beta-funaltrexamine (B-FNA: 1-20 micrograms), but not the mu1
      antagonist, naloxonazine (50 micrograms), dose-dependently reduced isoproterenol
      drinking. Both the kappa antagonist, nor-binaltorphamine (Nor-BNI, 5-20
      micrograms) and the delta1 antagonist, [D-Ala2, Leu5, Cys6]-enkephalin (DALCE, 1
      40 micrograms) also dose-dependently reduced isoproterenol drinking. These data
      implicate mu2, kappa and delta1 sites in the opioid modulation of isoproterenol
      drinking.

PMID- 7820635
TI  - Experimental beta beta'-iminodipropionitrile (IDPN) neuropathy: neurofilament
      profile of sensory, motor and autonomic nerves as seen by immunocytochemistry on
      whole-mount preparations.
AB  - IDPN-induced changes in a variety of sensory, motor and autonomic nerves were
      studied by whole-mount immunocytochemistry. A full range of proximo-distal
      accumulations of neurofilament-like material was found, from paranuclear round
      bodies in perikarya to distal and preterminal axonal dilations. Conversely, both
      terminal areas and nodal-paranodal regions of myelinated axons showed striking,
      sharply localized loss of neurofilament-immunostaining. The latter change, when
      transport of neurofilaments is halted by IDPN, may indicate their local
      processing and/or differential transport at nodal-paranodal regions.

PMID- 7820636
TI  - Inhibition of discharge in inferior colliculus, AII cortex and Ep cortex after
      presentations of click stimuli.
AB  - A temporally related reduction of discharge in response to 70-dB clicks was
      identified in secondary auditory (AII) cortex (48-56 ms after click), posterior
      ectosylvian (Ep) cortex (40-56 ms after click) and inferior colliculus (IC) (56
      76 ms after click). Units in primary auditory (AI) cortex, dorsal cochlear
      nucleus (DCN) and ventral cochlear nucleus (VCN) did not demonstrate a
      significant reduction of discharge at comparable periods. Neurons of AI cortex
      showed increased activity 36-40 ms after click. The timing of the periods of
      inhibited discharge in AII, Ep and IC, taken with the earlier activation of AI,
      supported the hypothesis of an inhibitory auditory pathway emanating from AI,
      affecting secondary auditory cortical regions and IC.

PMID- 7820637
TI  - Inhibition of the A1 area prevents hemorrhage-induced secretion of vasopressin in
      rats.
AB  - In rats, secretion of vasopressin initiated by hemorrhage was completely
      abolished after muscimol-induced inhibition of neuronal function in the A1 region
      of the ventrolateral medulla oblongata. The A1 neurons are essential links in the
      central pathway to hypothalamic vasopressin-synthesizing neurons in this species.

PMID- 7820638
TI  - Induction of Cu,Zn-superoxide dismutase after cortical contusion injury during
      hypothermia.
AB  - To determine the effect of hypothermia on superoxide injury after cerebral
      contusion, the induction of Cu,Zn-superoxide dismutase was examined 6 h after
      contusion in rats using Northern blotting. Cu,Zn-superoxide dismutase gene
      expression increased at the periphery of the contusion, which may indicate the
      severity of the superoxide stimulus. This increase was preserved after contusion
      under hypothermia, which may show that superoxide injury is still severe although
      brain edema is decreased.

PMID- 7820639
TI  - SCP application or B15 stimulation activates cAPK in the ARC muscle of Aplysia.
AB  - Application of small cardioactive peptide (SCP) or stimulation of motorneuron B15
      increases the level of activated cAMP-dependent protein kinase (cAPK) in the ARC
      muscle. SCP application also appears to induce a translocation of cAPK between
      different subcellular compartments of the ARC muscle and this translocation is
      also induced by cAMP addition to muscle homogenates. These results suggest that
      the actions of SCP in the Aplysia ARC neuromuscular system are mediated via the
      cAPK signal transduction pathway.

PMID- 7820640
TI  - Alterations of adenosine A1 receptors in morphine dependence.
AB  - The possibility that central adenosine A1 and A2a receptors mediate opiate
      dependence was examined in morphine-treated mice using radioligand binding
      methods. Mice treated with morphine for 72 h demonstrated significant increases
      in naloxone precipitated abstinence behaviors of jumping, wet-dog shakes, teeth
      chattering, forepaw trends, forepaw tremors and diarrhea compared to vehicle
      treated mice. Increased concentrations of cortical adenosine A1 receptor sites,
      but not striatal adenosine A2a sites, were found in saturation binding studies
      from morphine-dependent mice. Decreases in cortical A1 agonist binding affinity
      values along with increases in agonist binding sites were demonstrated in
      competition binding studies. These results suggest that adaptive changes of
      upregulation and sensitization of adenosine A1 receptors play a role in mediating
      the opiate abstinence syndrome.

PMID- 7820641
TI  - The role of corticosteroids in the acquisition of sensitization to locomotor
      stimulant effects of MK-801.
AB  - In the present study, we investigated the role of corticosterone and
      glucocorticoid receptors in the acquisition of sensitization to locomotor
      stimulant effects of MK-801 in rats. MK-801 (two doses, 0.4 mg/kg i.p. each,
      given twice, 48 h apart) evoked sensitization, observed as enhancement of the
      locomotor activity to a challenging dose of MK-801 (0.4 mg/kg) but not of a
      stereotypy-like activity. Pharmacological manipulations which deplete endogenous
      corticosterone, i.e., administration of the corticosterone synthesis inhibitor
      metyrapone (two injections, 150 and 50 mg/kg, given at 24 and 2 h before the
      first injection of MK-801, 4 mg/kg) or blockade of glucocorticoid receptors by
      administration of the antiglucocorticoid RU 38486 (20 mg/kg, 45 min before MK
      801, 0.4 mg/kg) abolished the acquisition of sensitization. The obtained results
      indicate that the endogenous corticosterone and glucocorticoid receptors (type
      II) are involved in the acquisition of sensitization to locomotor stimulant
      effects of MK-801. Final experiments showed that MK-801 in doses used in the
      present study (0.4 mg/kg) enhanced the plasma concentration of corticosterone and
      that single injection of exogenous corticosterone (10 mg/kg s.c.) enhanced the
      locomotor stimulant effects of MK-801 (0.2 mg/kg). The obtained data indicate
      that the acquisition of sensitization to locomotor stimulant effects of MK-801
      involves secretion of corticosteroids which probably act through glucocorticoid
      receptors, as was found previously for amphetamine and its congeners.

PMID- 7820642
TI  - A quantitative comparison on the effects of benztropine, cocaine and nomifensine
      on electrically evoked dopamine overflow and rate of re-uptake in the caudate
      putamen and nucleus accumbens in the rat brain slice.
AB  - Fast cyclic voltammetry has been used to study the relative importance of
      neuronal dopamine (DA) uptake and D2 autoreceptor stimulation on the control of
      the extracellular concentration of electrically evoked DA in rat brain slices
      containing aCPu and NAc. The degree of potentiation of DA overflow by
      benztropine, cocaine and nomifensine was always greater in the aCPu than in the
      NAc. Although EC50 values for the uptake blockers in the NAc were lower than in
      the aCPu, they were only significantly lower for 1 p with benztropine. One microM
      (-)-sulpiride, significantly potentiated DA overflow evoked by 20 p/20 Hz in both
      regions. In the presence of either 1 microM cocaine or 1 microM nomifensine,
      sulpiride further potentiated DA overflow in the NAc but not in the aCPu. The
      results indicate that in brain slices containing the aCPu, neuronal uptake is the
      main mechanism of controlling extracellular concentrations of DA due to
      electrical stimulation. Whilst in the NAc both uptake and D2 autoreceptor
      activation are important control mechanisms. The rate of removal of DA from the
      extracellular medium was not significantly different in the two regions but was
      decreased in the presence of (-)-sulpiride. This indicates that D2 receptors have
      a modulating effect on the DA neuronal uptake mechanism.

PMID- 7820643
TI  - Effect of pentobarbital on postischemic MK-801, muscimol, and naloxone bindings
      in the gerbil brain.
AB  - We investigated the postischemic alterations in [3H]MK-801, [3H]muscimol, and
      [3H]naloxone binding in the gerbil brain, and examined the effect of
      pentobarbital against these alterations. [3H]MK-801, [3H]muscimol, and
      [3H]naloxone were used to label N-methyl-D-aspartate (NMDA), gamma-aminobutyric
      acidA (GABAA), and opiate receptors, respectively. Transient cerebral ischemia
      was induced for 10 min, and pentobarbital (40 mg/kg) was administered
      intraperitoneally 30 min before ischemia. Five hours after ischemia, no
      conspicuous alteration in [3H]MK-801, [3H]muscimol, and [3H]naloxone binding was
      found in the striatum and hippocampus. Seven days after ischemia, [3H]MK-801 and
      [3H]naloxone binding was significantly decreased in the striatum and hippocampal
      area where histological neuronal damage was noted. By contrast, no significant
      change in [3H]muscimol binding was seen in the above regions except for the
      hippocampal CA3 sector. The treatment of pentobarbital caused a significant
      alteration in the binding of [3H]naloxone and [3H]muscimol in various brain areas
      5 h after ischemia. However, this drug showed no significant change in [3H]MK-801
      binding in the brain. Seven days after ischemia, pentobarbital partly ameliorated
      a significant reduction in [3H]MK-801 and [3H]naloxone binding in the striatum
      and hippocampus. A histological study also showed that pentobarbital afforded
      neuronal protection against the damage to the brain except for the hippocampal
      CA1 sector 7 days after ischemia. These results suggest that NMDA and opiate
      receptors are damaged after ischemia, whereas GABAA receptors are unaffected.
      They also demonstrate that opiate receptors are severe affected by the treatment
      of pentobarbital, compared with NMDA and GABAA receptors. These findings are of
      interest in relation to the mechanism of ischemic neuronal damage.

PMID- 7820644
TI  - Hippocampal corticosteroid receptor mRNA expression and spatial learning in the
      aged Wistar rat.
AB  - The expression of mineralocorticoid (MR) and glucocorticoid receptor (GR) mRNA in
      the hippocampus of aged (18-24 months) and young (7 months) Wistar rats in
      relation to spatial learning in the water maze was investigated. All aged rats
      showed impaired performance of the task to locate a hidden platform compared to
      young controls, but the Wistar strain as a whole showed inferior performance to a
      group of young Lister hooded controls (added for the purposes of comparison) with
      even young Wistar rats apparently failing to learn platform location. The aged
      Wistar rats spent nearly 70% of their time near the side walls of the pool
      throughout the 5 days of training, while the young Wistar controls showed a
      gradual reduction in the percentage time spent there. MR and GR mRNA expression
      were unaltered in any hippocampal subregion in aged rats compared to young
      controls. Plasma corticosterone levels were also unchanged in aged rats. These
      results show that alterations in hippocampal corticosteroid receptor gene
      expression are not an inevitable consequence of aging in the rat, but that aging
      may be associated with strategy changes in the performance of a spatial learning
      task that are independent of glucocorticoid hypersecretion or alterations in
      hippocampal corticosteroid receptor mRNA expression.

PMID- 7820645
TI  - Autoradiographic analysis of L- and N-type voltage-dependent calcium channel
      binding in canine brain after global cerebral ischemia/reperfusion.
AB  - Binding of antagonists to L- and N-type voltage-dependent calcium channels (VDCC)
      was measured in canine brain following global ischemia and reperfusion. Ischemia
      was induced by 10 min cardiac arrest, followed by restoration of spontaneous
      circulation for periods of up to 24 h. Binding of [3H]PN200-110 and [125I]omega
      conotoxin GVIA to frozen sections from hippocampus, striatum, parietal cortex and
      temporal cortex was analyzed using quantitative receptor autoradiography. The
      binding patterns of the two radioligands were similar in cortex and striatum, but
      differed in hippocampus. In the latter tissue, [125I]omega-conotoxin GVIA binding
      was dense over synaptic regions, especially the presynaptic polymorph layer of
      the dentate gyrus, but was virtually absent over cell body layers. In contrast,
      [3H]PN200-110 binding was more homogenously distributed, with highest binding in
      the molecular layer of the dentate gyrus. The binding of [125I]omega-conotoxin
      GVIA was not different from sham controls at any time point following cardiac
      arrest. [3H]PN200-110 binding was decreased in each region immediately following
      ischemia, recovering within 30 min of recirculation. These findings are in
      contrast to earlier findings of rapid increases in L-type VDCC binding to
      membrane fractions obtained from cortex and striatum in this model, and suggest
      that the previously detected increases may be due to a redistribution of channels
      from subcellular compartments to the plasma membrane during ischemia.

PMID- 7820646
TI  - Caudal portions of the spinal trigeminal complex are necessary for autonomic
      responses and display Fos-like immunoreactivity after corneal stimulation in the
      cat.
AB  - Corneal input to the spinal trigeminal nucleus (Vsp) was assessed by examining
      Fos-like immunoreactivity (Fos-LI) after chemical irritant stimulation by mustard
      oil in chloralose-anesthetized cats. The distribution of Fos-LI within the
      ipsilateral Vsp was bimodal: a dominant group of cells within the superficial
      laminae at caudal levels of subnucleus caudalis and a second group of cells
      within the ventrolateral pole of Vsp at obex levels and within the adjacent
      interstitial islands. Few Fos-positive cells were seen within the Vsp rostral to
      the mid-portion of subnucleus interpolaris or within the contralateral Vsp. To
      assess the involvement of caudal portions of the Vsp in mediating the adrenal and
      autonomic responses to corneal stimulation, mustard oil was applied before and
      after lidocaine blockade of the Vsp at obex levels in a second group of cats.
      Corneal stimulation alone increased significantly (P < 0.001) the adrenal
      secretion of catecholamines, adrenal blood flow, mean arterial pressure and heart
      rate. With the exception of heart rate, the adrenal and autonomic responses to
      mustard oil were greatly attenuated or abolished by lidocaine blockade of the
      ipsilateral Vsp at the level of the obex, a region that displayed a high number
      of Fos-positive cells after corneal stimulation. These results indicate that
      neurons within the Vsp at or more caudal than the level of the obex process
      chemical irritant input from the cornea and are necessary for corneal-evoked
      changes in adrenal and autonomic function.

PMID- 7820647
TI  - Glucocorticoid regulation of mRNA encoding (Na+K) ATPase alpha 3 and beta 1
      subunits in rat brain measured by in situ hybridization.
AB  - The effect of glucocorticoids on (Na+K)ATPase mRNA synthesis was studied in 19
      brain areas of adrenalectomized (ADX) rats untreated or receiving dexamethasone
      (DEX). For in situ hybridization, we employed a [35S]oligonucleotide probe for
      the alpha 3-subunit isoform, and a [3H]cDNA coding for the beta 1-subunit of the
      enzyme. Mean levels of grain density for the alpha 3 subunit mRNA of DEX-treated
      rats were significantly higher by a 't' test in medial septum, amygdala lateralis
      (AL) and medialis (AME), gyrus dentatus, CA4 hippocampal area, substantia nigra
      and periventricular gray, compared to untreated rats. For the beta 1-subunit,
      mean levels after DEX were significantly higher in AL and lateral preoptic area.
      In addition, the Kolmogorov-Smirnov test applied to frequency histograms of
      neuronal densities indicated a coordinate increase in alpha 3 and beta 1-subunit
      mRNA expression for the CA2 subfield and preoptic area medialis (POA MED). We
      conclude that (1) glucocorticoids are positive modulators of (Na+K)ATPase mRNA;
      (2) analysis of frequency histograms suggests that glucocorticoids promote in a
      few regions (AL, POA MED, CA2 subfield) a coordinate increase in the biosynthesis
      of the alpha 3 and beta 1-subunit mRNA. In 11 other areas stimulation occurs for
      one subunit mRNA only, whereas 5 areas were insensitive to glucocorticoid effects
      on this enzyme.

PMID- 7820648
TI  - Are ventromedial medulla neuronal properties modified by chronic peripheral
      inflammation? A single-unit study in the awake, freely moving polyarthritic rat.
AB  - In the present work, we recorded the neuronal properties of the ventromedial
      medulla, a brainstem structure involved in the descending spinal control systems
      related to nociception, in awake, freely moving healthy and polyarthritic rats.
      These animals were rendered polyarthritic with a subcutaneous administration of
      the Freund's adjuvant into the tail, and studied at 20 and 30 days post
      inoculation. At the ventromedial medulla level, the single-unit activities were
      recorded by means of a chronically implanted device supporting a 50 microns
      platinum-iridium wire as the recording electrode. With a total of 308 recorded
      neurons, we determined that in both healthy rats, i.e. animals having received
      mineral oil only and arthritic rats, there were ventromedial medulla units with
      common physiological properties, but also changes. In agreement with the results
      from anesthetized arthritic rats at spinal and thalamic levels, the systematic
      analysis of the responses to light touch and mechanical shock revealed that the
      'multimodal, multireceptive' units, excited by innocuous and noxious stimuli,
      were much more responsive to both modalities in arthritic rats. Approximately 7%
      of these neurons displayed a 'paroxysmal' spontaneous activity, also reported in
      the literature for other structures. In addition, we recorded a significant
      number of neurons inhibited or excited-inhibited by innocuous and noxious
      cutaneous stimulations, and a few with a regular spontaneous activity, also
      responding, which has never been the case in healthy rats. We conclude that a
      peripheral chronic inflammation, such as arthritis, can produce changes of the
      ventromedial medulla neuronal properties, as compared to healthy animals.
      Consequently, in addition to its classical role in the spinal control of
      nociception, the ventromedial medulla is able to develop some form of plasticity
      in the case of persistent pain of peripheral origin.

PMID- 7820649
TI  - Monoamine vesicular uptake sites in patients with Parkinson's disease and
      Alzheimer's disease, as measured by tritiated dihydrotetrabenazine
      autoradiography.
AB  - The monoaminergic innervation of the caudate nucleus, putamen and ventral
      striatum was investigated post mortem, in patients with Parkinson's and
      Alzheimer's disease as compared to control subjects, by autoradiographic
      detection of tritiated dihydrotetrabenazine (3H-TBZOH), a specific high affinity
      ligand of the vesicular monoamine transporter. The binding of 3H-TBZOH was
      specific and saturable (Kd 5.3 nM). In control striatum, the pattern of
      distribution of 3H-TBZOH binding was heterogeneous, with higher binding levels in
      the 'matrix' than in the 'striosome' compartment. Changes in ligand binding
      levels were observed in the pathological brains compared to controls. In
      Parkinson's disease (PD), characterized by a severe damage of mesostriatal
      dopaminergic neurons, the density of 3H-TBZOH binding was reduced. A severe
      decrease in 3H-TBZOH binding was observed in all parts of the striatum (caudate
      nucleus: -80%, putamen: -86%, ventral striatum: -94%) in PD brains. The data
      corroborate the deficiency in striatal dopaminergic transmission and suggest that
      in PD brains dopaminergic terminals have disappeared and/or no longer contain
      synaptic vesicles. In Alzheimer's disease (AD), 3H-TBZOH binding was
      significantly reduced by 57% in the ventral striatum and not in the caudate
      nucleus and putamen. The specific decrease of monoaminergic transporter levels in
      the ventral striatum confirm that this nucleus is a target area in AD.

PMID- 7820650
TI  - (2S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl) glycine positively modulates
      metabotropic glutamate receptors coupled to polyphosphoinositide hydrolysis in
      rat hippocampal slices.
AB  - In rat hippocampal slices, the novel metabotropic glutamate receptor (mGluR)
      ligand, (1S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV) enhanced
      the stimulation of polyphosphoinositide (PPI) hydrolysis elicited by quisqualate
      or by submaximal concentrations of ibotenate or (1S,3R)-1-aminocyclopentane-1,3
      dicarboxylic acid (1S,3R-ACPD). The enhancing effect of DCG-IV was (i) specific
      for mGluR agonists, (ii) restricted to hippocampal slice preparation, (iii)
      reversible, and (iv) not subject to homologous desensitization, in addition, DCG
      IV did not interact with L-2-amino-4-phosphonobutanoate (AP4), a noncompetitive
      antagonist of mGluRs coupled to PPI hydrolysis in brain slices [32]. The action
      of DCG-IV on quisqualate-stimulated PPI hydrolysis was insensitive to antagonists
      of ionotropic glutamate receptors and did not appear to be a consequence of a
      reduction in the intracellular levels of cAMP [14]. When the stimulation of PPI
      hydrolysis was measured as a function of the incubation time, DCG-IV potentiated
      quisqualate-stimulated PPI hydrolysis after 60 min of incubation, when
      quisqualate had already reached its maximal effect. Knowing that activation of
      protein kinase C (PKC) limits the extent of mGluR agonist-stimulated PPI
      hydrolysis over time, we have studied the enhancing effect of DCG-IV in the
      presence of the PKC activator, 12-O-tetradecanoylphorbol-13-acetate (TPA). As
      expected [9], TPA reduced quisqualate-stimulated PPI hydrolysis in control
      slices, but was inactive in slices incubated in the presence of DCG-IV. Taken
      collectively, these results suggest that DCG-IV positively modulates the activity
      of mGluRs coupled to PPI hydrolysis through a mechanism, which involves PKC
      mediated phosphorylation processes.

PMID- 7820651
TI  - Protein content and cAMP-dependent phosphorylation of fractionated white perch
      retina.
AB  - In the retinas of teleost fish dopamine, released from interplexiform cells,
      modulates synaptic transmission at both the chemical and electrical synapses of
      retinal horizontal cells. This modulation is due to activation of adenylate
      cyclase and phosphorylation by protein kinase A, perhaps of the synaptic ion
      channel proteins themselves. In this study we have fractionated the white perch
      retina by Percoll density gradient centrifugation in order to identify proteins
      which coenrich with horizontal cells. In addition we have tested retinal
      fractions for phosphorylation by native cAMP-dependent kinase. Our findings
      indicate that there are at least 3 proteins of molecular weights 28, 43/44 and 50
      kDa which coenrich with horizontal cells and 3 proteins of 30/31 kDa, 35 kDa
      (putative rhodopsin) and 48 kDa (putative arrestin) which coenrich with
      photoreceptor fractions. The 43/44 kDa phosphoprotein is a target for cAMP
      dependent protein phosphorylation and thus is apparently an element of the
      dopaminergic modulatory pathway in perch horizontal cells.

PMID- 7820652
TI  - Direct measurement of glutamate release in the brain using a dual enzyme-based
      electrochemical sensor.
AB  - The in vivo measurement of the rapid changes in the extracellular concentrations
      of L-glutamic acid in the mammalian brain during normal neuronal activity or
      following excessive release due to episodes of anoxia or ischemia has not been
      possible to this date. Current techniques for the measurement of the release of
      endogenous glutamate into the extracellular space of the central nervous system
      are relatively slow and do not measure the actual concentration of free glutamate
      in the extracellular space. An enzyme-based electrode with rapid response times
      (about 1 s) and high degree of sensitivity (less than 2 microM) and selectivity
      for L-glutamic acid is described in this paper. This electrode has both L
      glutamate and ascorbate oxidase immobilized on its surface. The latter enzyme
      removes almost completely any interferences produced by the high levels of
      extracellular ascorbate present in brain tissue. The response of the electrode to
      glutamate and other potentially interfering substances was fully characterized in
      vitro and its selectivity, sensitivity and rapidity in responding to a rise in
      extracellular glutamate concentrations was also demonstrated in vivo. Placement
      of the electrode in the dentate gyrus of the hippocampus led to the detection of
      both KCl-induced release of L-glutamic acid and the release induced by
      stimulation of the axons in the perforant pathway. The development of this
      selective, sensitive and rapidly responding glutamate sensor should make it now
      possible to measure the dynamic events associated with glutamate
      neurotransmission in the central nervous system.

PMID- 7820653
TI  - Effects of the lipid peroxidation inhibitor tirilazad mesylate (U-74006F) on
      gerbil brain eicosanoid levels following ischemia and reperfusion.
AB  - The present study measured the production of eicosanoids in the gerbil brain
      during early reperfusion after either a 3-h unilateral carotid occlusion (UCO,
      model of focal ischemia) or a 10-min bilateral carotid occlusion (BCO, model of
      global ischemia). Arachidonic acid (AA) metabolites were examined to determine if
      pretreatment with the 21-aminosteroid lipid peroxidation inhibitor U-74006F
      (tirilazad mesylate) could influence postreperfusion synthesis of brain
      eicosanoids. In the 3-h UCO focal ischemia model, there was an early (5-min)
      postreperfusion elevation in brain levels of PGF2 alpha, TXB2 and LTC4 (P < 0.05
      vs. sham for all three eicosanoids). LTB4 also rose but not significantly. On the
      other hand, PGE2 and 6-keto-PGF1 alpha tended to decrease during ischemia and at
      5-min postreperfusion (P < 0.05 vs. sham for PGE2). Pretreatment with known
      neuroprotective doses of U-74006F in this model (10 mg/kg i.p. 10 min before and
      again immediately upon reperfusion) did not affect the increase in PGF2 alpha or
      TXB2 but significantly blunted the elevations in LTC4 and LTB4. The
      postreperfusion decrease in PGE2 was also attenuated. In the 10-min BCO global
      ischemia model, there was also an increase in each of the measured eicosanoids,
      except LTB4, at 5 min after reperfusion. Pretreatment with U-74006F (10 mg/kg
      i.p. 10 min before ischemia) selectively decreased the rise in LTC4 but did not
      significantly affect the other eicosanoids. In contrast, the antioxidant actually
      caused a significant enhancement of the postreperfusion increase in PGE2 vs.
      vehicle-treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7820654
TI  - Rat substantia nigra pars reticulata neurones are tonically inhibited via GABAA,
      but not GABAB, receptors in vitro.
AB  - Extracellular single unit recordings were made from substantia nigra pars
      reticulata (SNr) neurones in slices of rat brain. Cells fired spontaneous action
      potentials at 11.4 +/- 0.8 Hz. The GABAA receptor agonist isoguvacine (1-10
      microM) reduced firing rate in a concentration-dependent manner [50% of maximal
      inhibition (IC50) with 3.2 microM], as did the GABAB agonist baclofen (0.3-10
      microM; IC50 1.4 microM). The GABAA antagonist bicuculline (30 microM) not only
      blocked the action of isoguvacine, but also increased the basal firing rate to
      187.5 +/- 12.6% of control. The GABAB antagonist CGP 55845A (0.1 microM), while
      blocking the inhibitory action of baclofen, was without effect on spontaneous
      firing rate, as was strychnine (10 microM), the antagonist of glycine and
      taurine, and also Met-enkephalin (10 microM). Tiagabine (50 microM), the blocker
      of GABA uptake, caused an inhibition of firing which could be reversed with
      bicuculline (30 microM) but not CGP 55845A (1 microM). We conclude that the
      firing rate of SNr neurones is under tonic inhibition by GABA in vitro, which can
      be relieved by antagonists of GABAA, but not GABAB receptors, and enhanced by
      blockade of GABA reuptake. The source of this GABA tone is likely to be from
      recurrent axon collaterals of SNr neurones themselves.

PMID- 7820655
TI  - Spinal cord-skeletal muscle cografts: trophic and functional interactions.
AB  - Skeletal muscle from embryonic day 20 (E20) was combined with E15 rat spinal cord
      in the anterior chamber of the eye of adult albino rats. The two grafts were
      either transplanted concomitantly or sequentially, in which case muscle tissue
      was added 4 months after the spinal cord. Control groups received a single graft
      of either spinal cord or skeletal muscle. Survival and intraocular growth were
      observed through the cornea. After maturation in oculo, the double grafts were
      examined immunohistologically utilizing antisera to neurofilament (NF) and
      acetylcholinesterase (AChE). The grafts were also evaluated using electrical
      stimulation to determine functional connectivity. The spinal cord and skeletal
      muscle grafts were found to exert reciprocal trophic effects on each other,
      evidenced as a larger muscle mass in skeletal muscle grafts allowed to develop in
      the presence of spinal cord tissue, and a larger volume of spinal cord grafts
      allowed to develop together with a skeletal muscle graft, respectively.
      Immunohistochemistry revealed NF-positive nerve fibers leaving the spinal cord
      graft and entering the muscle tissue. AChE-positive endplates developed in the
      muscle grafts. Electrical stimulation of the spinal cord part of double-graft
      combinations generally elicited contractile responses in specific areas of the
      muscle cograft. These results demonstrate both structural and functional
      connections between grafts of spinal cord and skeletal muscle tissue in vivo. The
      fact that such connections were also established between a mature (adult) spinal
      cord graft and fetal skeletal muscle tissue suggests that some alpha-motoneurons
      are able to survive for many months in the intraocular grafts without an
      appropriate target, and that they are able to subsequently innervate skeletal
      muscle targets.

PMID- 7820656
TI  - The ontogeny of [3H]gamma-hydroxybutyrate and [3H]GABAB binding sites: relation
      to the development of experimental absence seizures.
AB  - gamma-Hydroxybutyric acid (GHB) is a naturally occurring compound which has the
      ability to induce generalized absence seizures when given to animals. There is
      growing evidence that both gamma-aminobutyric acid (GABA)B- and GHB-mediated
      mechanisms are involved in the pathogenesis of this phenomenon. Because of the
      fact that absence seizures are a disorder of children the ontogeny of [3H]GHB and
      [3H]GABAB binding and the developmental appearance of absence seizures in the GHB
      model of absence was ascertained and compared in developing rats. [3H]GABAB
      binding was present within the first 3 days of postnatal life and rose to levels
      which exceeded those found in adults, peaking between the 3rd and 5th postnatal
      week. [3H]GHB binding on the other hand did not appear until postnatal day 17
      when it was detectable in the CA1 region of the hippocampus. There was a steady
      increase in [3H]GHB binding until adult levels were reached by postnatal day 40.
      Comparison of [3H]GABAB and [3H]GHB binding revealed that both sites were common
      to layer I-III of cortex, but otherwise differed in their regional distribution.
      There was an absolute concordance of the ontogeny of GHB-induced absence seizures
      with the developmental appearance of [3H]GHB binding in the superficial laminae
      of cortex; both appeared at postnatal day 18. These data support the hypotheses
      that the [3H]GHB and [3H]GABAB binding sites are separate from one another and
      suggest that maturational events in thalamus and cortex in the 3rd postnatal week
      are involved in the expression of GHB-induced absence seizures.

PMID- 7820657
TI  - Regional suppression by water intake of c-fos expression induced by
      intraventricular infusions of angiotensin II.
AB  - Intracerebroventricular (i.c.v.) infusions of angiotensin II (AII) reliably
      induced c-fos expression in the supraoptic (SON) and paraventricular (PVN)
      nuclei, as well as other areas of the basal forebrain including the OVLT,
      subfornical organ (SFO), and bed nucleus (BNST). Double-labelling showed that AII
      induced c-fos was observed in both vasopressin (AVP-) and oxytocin (OXY)
      containing neurons of the SON and PVN in male rats. Allowing rats to drink water
      after AII infusions suppressed c-fos expression both AVP- and OXY-stained
      magnocellular neurons. Intragastric infusions of water were also effective,
      showing that oro-pharyngeal stimuli were not critical. Maximal suppression
      occurred in rats in whom water had been infused intragastrically about 5 min
      before i.c.v. AII infusions, suggesting that changes in osmolarity were
      responsible. i.c.v. AII also induced c-fos expression in a number of brainstem
      structures, including the solitary nucleus (NTS), lateral parabrachial nucleus
      (LPBN), locus coeruleus (LC), and the area postrema (AP). These results indicate
      that AVP and OXY-containing neurons in the magnocellular parts of the SON and PVN
      alter their immediate-early gene response to AII after water intake, and that
      this does not depend upon oro-pharyngeal factors. Furthermore, AII can induce c
      fos expression in a number of brainstem nuclei associated with autonomic
      function, and these do not respond to water intake.

PMID- 7820658
TI  - Astrocytic contribution to functioning synapse formation estimated by spontaneous
      neuronal intracellular Ca2+ oscillations.
AB  - Glial contribution to in vitro synaptic function was investigated in a neuron
      glia co-culture system by monitoring spontaneous oscillations of intracellular
      Ca2+ in neurons. Rat cortical neurons, grown stably on a cortical astrocyte
      monolayer, extended neurites resulting in marked functional synapse formation.
      Little synapse formation was observed in neuronal co-culture with meningeal
      fibroblasts or endothelial cells. Aged astrocytes in vitro (C35) were found to
      attenuate synaptic development, while young astrocytes (C5) markedly promoted
      synaptic function. C5 and C35 astrocyte media conditioned yielded no significant
      synaptogenic effect, indicating diffusible factor(s) are not responsible for our
      observation. Modulation of astrocytic proliferation and differentiation by
      gliostatin, a glial growth inhibitor, or dibutyryl cAMP affected neuronal
      synaptic function on the co-cultures. Site-specific analysis in homologous and
      heterologous neuron-astrocyte co-cultures among cortex, hippocampus, septum, and
      striatum revealed that homologous combinations of neurons and astrocytes derived
      from identical brain regions elicited the largest number of synchronizing
      neurons. These results suggest that in vivo neuronal synaptic function
      essentially requires the participation of adjacent astrocytes, which is site
      specific and age-dependent.

PMID- 7820659
TI  - Sensitization to cocaine's motor activating properties produced by electrical
      kindling of the medial prefrontal cortex but not of the hippocampus.
AB  - A substantial body of evidence has accumulated that implicates NMDA systems in
      the neural changes that are associated with the development of both electrical
      kindling of limbic sites and sensitization to the behavioral effects of repeated
      stimulant exposure. This study sought to establish whether electrical kindling of
      the brain was a sufficient condition for inducing sensitization to cocaine's
      motor activating effects and, if so, whether the cross sensitization was a result
      of kindling of a specific locus. Rats received daily electrical stimulation of
      either the medial prefrontal cortex or the hippocampus. Other rats received the
      electrode implants and were handled daily but received no electrical stimulation.
      Stage 5 seizures developed in response to the stimulation in 32-35 days. Once
      this criterion of kindling was established and following a 14 day waiting period
      the effectiveness of cocaine (0.0, 5.0 or 10.0 mg/kg) in elevating horizontal
      motor activity was determined. For all 3 groups (sham controls, prefrontal
      cortical and hippocampal stimulated rats) cocaine produced a dose-dependent
      increase in horizontal activity. The sham controls and hippocampal rats did not
      differ in the magnitude of the cocaine-produced effect. However, rats that had
      received stimulation of the prefrontal cortex showed heightened levels of cocaine
      induced activity that were particularly apparent in response to 10.0 mg/kg
      cocaine. These data suggest that kindling of the prefrontal cortex had sensitized
      rats to the behavioral effects of cocaine.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7820660
TI  - Specific distribution of Ca2+/calmodulin-dependent protein kinase II alpha and
      beta isoforms in some structures of the rat forebrain.
AB  - The immunohistochemical distribution of Ca2+/calmodulin-dependent protein kinase
      II (CaM kinase II) alpha and beta isoforms in the rat forebrain was examined by
      using monoclonal antibodies specific to each isoform. The present study confirmed
      that alpha and beta immunoreactivities are localized only in neuronal elements.
      At the light microscopic level, specific distribution patterns of these isoforms
      and staining characteristics were recognized in some regions of the forebrain as
      follows. Firstly, alpha-immunoreactive neurons were more homogeneously
      distributed throughout the cellular layers of the cerebral cortex (i.e., layers
      II-VI) than beta-immunoreactive ones. Secondly, neurons in the globus pallidus
      were immunostained by the anti-beta antibody, but not by the anti-alpha antibody.
      Thirdly, neurons in the medial habenular nucleus, the subthalamic nucleus and the
      reticular thalamic nucleus were more densely stained with the anti-beta antibody
      than with the anti-alpha antibody. However, marked differences were not observed
      in the hippocampal formation at the light microscopic level. The electron
      microscopic analysis of the cerebral cortex demonstrated that subcellular
      localizations of alpha- and beta-immunoreactive products within the cortical
      neurons were quite dissimilar: (i) the nucleus was stained only with the anti
      alpha antibody, but not with the anti-beta antibody, and (ii) beta-immunoreactive
      products were more sporadically localized in the cytoplasms of the perikarya and
      dendrites than the alpha-immunoreactive ones. These regional and subcellular
      differences between the distribution patterns of alpha and beta
      immunoreactivities suggest the functional diversity of CaM kinase II alpha and
      beta isoforms in the central nervous system.

PMID- 7820661
TI  - GABAergic regulation of tuberoinfundibular dopaminergic neurons in the male rat.
AB  - The purpose of the present study was to examine the effects of gamma-aminobutyric
      acid (GABA)A and GABAB receptor blockade and activation on the activity of
      tuberoinfundibular dopaminergic (TIDA) neurons in male rats. The activity of TIDA
      neurons was estimated by measuring the concentration of the primary dopamine
      metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in the median eminence.
      Administration of the GABAA receptor antagonist SR 95531 increased DOPAC
      concentrations in the median eminence, and decreased plasma concentrations of
      prolactin, in a dose- and time-related manner. Administration of the GABAA
      receptor agonist isoguvacine had no effect per se on DOPAC concentrations in the
      median eminence, but produced a delayed decrease in plasma prolactin
      concentrations. Isoguvacine pre-treatment prevented the increase in DOPAC
      concentrations in the median eminence produced by SR 95531. In contrast,
      administration of the GABAB receptor agonist baclofen decreased DOPAC
      concentrations in the median eminence, and increased plasma prolactin
      concentrations in a dose-dependent manner. Administration of the GABAB receptor
      antagonist 2-hydroxysaclofen had no effect on TIDA neurons per se, but blocked
      baclofen-induced decreases in DOPAC concentrations in the median eminence and
      increases in plasma prolactin concentrations. These results indicate that while
      activation of GABAB receptors inhibits TIDA neurons, these neurons are tonically
      inhibited by endogenous GABA acting at GABAA but not GABAB receptors.

PMID- 7820662
TI  - Neurochemical identification of A13 dopaminergic neuronal projections from the
      medial zona incerta to the horizontal limb of the diagonal band of Broca and the
      central nucleus of the amygdala.
AB  - Studies utilizing fluorescent histochemical techniques first revealed that A13
      dopaminergic (DA) perikarya located in medial zona incerta (MZI) project to
      various regions within the hypothalamus; accordingly, these DA neurons were
      designated the 'incertohypothalamic' DA neuronal system. More recently, it has
      been shown that the anterograde neuronal tract tracer Phaseolus vulgaris
      leucoagglutinin, after injection into MZI, is identified in nerve terminals
      outside of the hypothalamus; for example, in horizontal limb of the diagonal band
      of Broca (HDB) and central nucleus of the amygdala (cAMY). The purpose of the
      present study was to determine, using neurochemical techniques, if A13 DA neurons
      project to the HDB and cAMY. Concentrations of dopamine and one of its
      metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) were determined in HDB and
      cAMY following: (1) electrical stimulation of MZI, (2) electrolytic lesion or
      knife ablation of MZI, and (3) administration of gamma-hydroxybutyric acid (GHBA)
      into MZI. For comparison, similar measurements were made in nucleus accumbens (N.
      Acc.), a terminal region of A10 DA neurons in the ventral tegmental area (VTA).
      Electrical stimulation of MZI increased DOPAC concentrations in HDB and cAMY,
      whereas electrolytic or ablative lesions of MZI decreased dopamine concentrations
      in both of these regions. By contrast, neither stimulation nor lesion of MZI had
      any effect on DOPAC or dopamine concentrations in N. Acc. Intracerebral injection
      of GHBA into MZI increased dopamine concentrations in MZI and HDB, but not in
      cAMY or N. Acc. Intracerebral administration of GHBA into VTA increased dopamine
      concentrations in HDB and N. Acc., but not in MZI or cAMY.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7820663
TI  - Effect of diabetes mellitus on responses of the rat basilar artery to activation
      of beta-adrenergic receptors.
AB  - The goal of this study was to determine whether diabetes mellitus alters
      reactivity of the basilar artery in vivo to activation of beta-adrenergic
      receptors. We measured diameter of the basilar artery in non-diabetic and
      diabetic (streptozotocin 50-60 mg/kg i.p.) rats during superfusion with
      isoproterenol and norepinephrine, which dilate cerebral blood vessels via
      activation of beta-adrenergic receptors. Dilatation of the basilar artery in
      response to isoproterenol and norepinephrine was significantly less in diabetic
      compared to non-diabetic rats. To determine whether impaired dilatation of the
      basilar artery in diabetic rats in response to isoproterenol and norepinephrine
      was related to an alteration in catalytic activity of adenylate cyclase, we
      examined dilatation of the basilar artery in response to forskolin, a direct
      activator of adenylate cyclase. In contrast to that observed for isoproterenol
      and norepinephrine, forskolin produced similar dilatation of the basilar artery
      in non-diabetic and diabetic rats. Thus, the findings of the present study
      suggest that diabetes mellitus impairs dilatation of the basilar artery in vivo
      in response to activation of beta-adrenergic receptors. In addition, impairment
      of beta-adrenergic mediated dilatation of the basilar artery during diabetes
      mellitus does not appear to be related to an alteration in catalytic activity of
      adenylate cyclase.

PMID- 7820665
TI  - Mechanism of the hippocampal loss of adenosine sensitivity in calcium-free media.
AB  - Adenosine depresses the excitability of pyramidal neurones in the hippocampus.
      This effect is lost in calcium-free media and we have now investigated the
      mechanism of this. Extracellular recordings were made of antidromically and
      orthodromically evoked population potentials from CA1 region of rat hippocampal
      slices. It was observed that the activity of adenosine can be restored in the
      presence of procaine or carbamazepine, known inhibitors of sodium channels. The
      GABAB agonist baclofen was able to depress potential size but did not restore
      sensitivity to adenosine. It is concluded that the loss of postsynaptic
      sensitivity to adenosine in calcium-free solution results from the increased
      sodium conductances.

PMID- 7820664
TI  - Potentially amyloidogenic fragment of 50 kDa and intracellular processing of
      amyloid precursor protein in cells cultured under leupeptin.
AB  - The principal neuropathological feature of Alzheimer's disease is extracellular
      deposition of approximately 4-kDa proteinous fragment, designated as beta-amyloid
      peptides (beta/A4 peptides) derived by proteolytic cleavage from amyloid
      precursor protein (APP), a large cell-surface receptor-like protein. There has
      been evidence that APP is proteolytically degraded in the secretory and
      endosomal/lysosomal pathways. The pathway in which APP is cleaved to generate
      beta/A4 peptides is still not identified. To clarify the intracellular processing
      of APP into the generation of beta/A4 peptides, we detected and characterized
      potentially amyloidogenic or non-amyloidogenic fragments using newly established
      monoclonal and polyclonal antibodies in the cultured cells with or without
      leupeptin, potent lysosomal protease inhibitor of lysosome. APP fragments of 50
      and 20 kDa containing full-length beta/A4 peptides were identified in the
      cultured cells. Immunoblot analysis, biochemical study for specific marker enzyme
      activity of the fractions obtained from subcellular fractionation, sucrose
      density gradient centrifugation indicated that the 50-kDa APP fragment was
      produced in the compartment closely related to endosomal/lysosomal system. Our
      data suggest that the endosomal/lysosomal pathway is involved in the processing
      and generation of beta/A4 peptides.

PMID- 7820667
TI  - A period (per)-like protein exhibits daily rhythmicity in the suprachiasmatic
      nuclei of the rat.
AB  - The period (per) gene of Drosophila melanogaster is considered an important
      biological clock gene, since it regulates multiple behavioral rhythms. Per mRNA
      and protein exhibit circadian rhythms in the fruitfly brain and these rhythms
      appear to influence each other through a feedback loop. More recently, using the
      same antibody as was used in the Drosophila studies, PER-like proteins were
      detected in the suprachiasmatic nuclei (SCN) of male rats. This region of the
      brain is considered to be a major neural circadian pacemaker in mammals. The
      purpose of this study was to confirm that PER-like proteins are detectable in the
      SCN of female rats and to determine whether PER-like proteins exhibit a circadian
      rhythm. Female rats were killed at several times of day under both light/dark and
      constant conditions. Using the same anti-PER antibody in Western blots with
      Enhanced Chemiluminescence (Western-ECL) detection, the levels of the PER-like
      proteins were quantified in the SCN and cerebral cortex. The antibody identified
      a doublet band of approximately 170-160 kDa and a single band at 115 kDa. Of the
      three PER-like proteins only the largest exhibited a daily rhythm in the SCN,
      which peaked in the middle of the dark and attained its nadir around lights off;
      levels during the light were intermediate with a tendency towards a second drop
      around lights on. This rhythm did not persist under constant dim red
      light.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7820666
TI  - TNF-alpha increases the frequency of spontaneous miniature synaptic currents in
      cultured rat hippocampal neurons.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a cytokine secreted by activated
      astrocytes and is known to alter evoked synaptic activity in slices of adult rat
      hippocampus. In this paper we show that TNF-alpha increases the frequency of
      spontaneous miniature synaptic currents in cultured hippocampal neurons, acting
      at nanomolar concentrations. In addition, we show that the mRNA for the 55 kDa
      TNF-alpha receptor (TNF-R1) is detected in embryonic rat hippocampal cultures, as
      well as in acutely dissected embryonic and adult rat hippocampi. Possible
      transduction pathways mediating the TNF-alpha effect are discussed.

PMID- 7820668
TI  - Antibodies to reduced glutathione.
AB  - Reduced glutathione was conjugated to carrier proteins with glutaraldehyde.
      Conjugates were reduced by sodium borohydride and injected into rabbits. Using an
      enzyme-linked immunosorbent assay, antibody affinity and specificity were
      determined by competition experiments between glutathione conjugate and related
      conjugated compounds. The resulting cross-reactivity ratios, calculated at half
      displacement, showed that conjugated glutathione was the best recognized
      compound. Non-reduced glutathione conjugate was 50 x less recognized. The other
      related conjugates were not recognized at all. Thus, the high affinity and
      relative specificity make these antibodies potentially valuable tools for
      immunohistochemical detection of reduced glutathione in glutaraldehyde-fixed rat
      brain. Using purified antisera diluted at 1/5000, reduced glutathione was
      preferentially visualized in nerve fibers of cortex, cerebellum and spinal cord.
      These results suggest that concentration of GSH in rat CNS are higher in nerve
      fibers than in neuronal perikaryons.

PMID- 7820669
TI  - Sigma (12-16 Hz) and beta (20-28 Hz) EEG discriminate NREM and REM sleep.
AB  - All night sleep EEG from ten normal students were subjected to FFT spectral
      analyses. Delta (0.3-3 Hz), sigma (12-16 Hz) and beta (20-28 Hz) EEG showed
      strongly oscillating patterns across the night. The scattergram of sigma versus
      beta revealed two separate clusters. One cluster demonstrated a positive linear
      correlation between sigma and beta. The second cluster showed a range of beta,
      but a stable, low level of sigma activity. Points in the former cluster consisted
      of those from NREM epochs, and in the latter, from REM epochs. The present
      results suggest that REM and NREM EEG are composed of two sets of EEG frequency
      components, perhaps reflecting different neuronal pools.

PMID- 7820671
TI  - Adrenocorticotropin and growth hormone secretions after intracerebroventricular
      administration of neostigmine in rats: their relationships to hypothalamic
      monoaminergic neuronal activities.
AB  - Serum adrenocorticotropic hormone (ACTH) and growth hormone (GH) concentrations
      were assessed simultaneously with hypothalamic neuronal activities of
      norepinephrine (NE), dopamine (DA), and serotonin (5-HT) 60 min after the third
      cerebroventricular administration of neostigmine (a cholinesterase inhibitor) in
      awake rats. Serum ACTH and GH concentrations were significantly increased and
      decreased, respectively. Neostigmine caused significant increases in hypothalamic
      NE and DA activities and a significant decrease in hypothalamic 5-HT activity.
      The reciprocal changes of serum ACTH and GH concentrations were similar to those
      of hypothalamic NE and 5-HT activities. Multiple regression analyses with
      stepwise procedure revealed that hypothalamic NE and 5-HT activities were
      respectively significant determinants of serum ACTH and GH concentrations. Apart
      from the direct influence of neostigmine on ACTH and GH secretions, it is
      suggested that the changes in hypothalamic monoaminergic activities play an
      important role in modulating ACTH and GH secretions following the administration
      of neostigmine.

PMID- 7820670
TI  - Intraventricular administration of a FIV-envelope protein induces sleep
      architecture changes in rats.
AB  - Fifteen adult male Sprague-Dawley rats were implanted with a set of electrodes
      for standard sleep recordings. A stainless steel cannula was also implanted into
      the lateral ventricle of these rats. Fifteen additional rats were implanted with
      a cannula alone. Rats with electrodes were habituated for 3 days or more to the
      recording environment, then placed into 3 groups (n = 5). One group received
      saline (i.c.v.), while the other two groups received either the feline
      immunodeficiency virus envelope glycoprotein (FIV SU-Env) or a fragment of the
      Epstein-Barr virus envelope glycoprotein (EB gp105). Rats were then recorded for
      electrographic sleep-wake cycle evaluation for the following 4 h. Core
      temperature was assessed through a thermistor probe inserted into the rectum,
      immediately before and 1, 2, 3 and 4 h after the i.c.v. treatment condition.
      Results demonstrated that compared to saline, FIV SU-Env increased wakefulness
      and decreased REM sleep throughout the 4 h of recording. Likewise, FIV SU-Env
      decreased SWS2 for 2 h. In addition, EB gp105 administration elicited minor
      modifications of the sleep-wake cycle, causing only a transient reduction of REM
      sleep in the first hour of recording. None of the treatments altered body
      temperature. These findings strongly support and extend studies in FIV-infected
      cats in which we have found similar sleep abnormalities. In addition, these
      results are consistent with the hypothesis that the FIV SU-Env proteins are
      responsible for these neurological disturbances.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7820672
TI  - Functional anatomy of taste perception in the human brain studied with positron
      emission tomography.
AB  - Regional cerebral blood flow (rCBF) was measured with positron emission
      tomography (PET) in 10 normal volunteers with the purpose of measuring rCBF
      changes related to taste physiology. Discrimination of 0.18% saline from pure
      water was associated with significantly increased rCBF values in the thalamus,
      the insular cortex, the anterior cingulate gyrus, the parahippocampal gyrus, the
      lingual gyrus, the caudate nucleus, and the temporal gyri. The results indicate
      that rCBF changes in these structures may reflect oral exposure to salt.

PMID- 7820673
TI  - trkB-like immunoreactivity in rat dorsal root ganglia following sciatic nerve
      injury.
AB  - The expression of full-length trkB protein, the functional high affinity receptor
      for BDNF and NT-4, was examined by immunohistochemistry in adult rat L4-L5 dorsal
      root ganglia after different types of sciatic nerve lesions. In normal ganglia,
      52.5% of the neurons showed trkB-like immunoreactivity. Size measurements
      demonstrated that trkB-like immunoreactivity was seen predominantly in small- and
      medium-sized cells. This was confirmed by the finding that 28% of all trkB
      positive neurons showed affinity to RT97, an antibody which labels a
      neurofilament epitope specific for medium-sized and large primary afferent
      neurons. After crush, section or neuroma formation of the sciatic nerve, the
      proportion of trkB-positive cells was 64.5%, 58% and 61.9%, respectively. Since
      trkB-receptors are present in regenerating primary afferent neurons, these data
      could indicate that BDNF and/or NT-4 are involved in sensory nerve fiber
      regeneration after adult injury.

PMID- 7820674
TI  - Copper/zinc superoxide dismutase mRNA levels are increased in sporadic
      amyotrophic lateral sclerosis motorneurons.
AB  - Mutations of the Cu/Zn superoxide dismutase (SOD-1) gene were recently implicated
      in the pathogenesis of familial amyotrophic lateral sclerosis (ALS). We measured
      SOD-1 mRNA levels in motorneurons of the more common sporadic form of the disease
      and found a 42% increase in ALS motorneurons (P = 0.058) as compared with
      controls. These results suggest that oxidative stress may also play a role in the
      pathogenesis of sporadic ALS.

PMID- 7820675
TI  - Immunocytochemical distribution of the brain glucose transporter (GLUT 1) in
      experimental gliosis.
AB  - The present study has examined the immunocytochemical expression of the blood
      brain barrier glucose transporter GLUT 1 as compared with GFAP in models of
      experimental gliosis. In neocortical grafts, gliosis was prominent at the graft
      host interface mostly associated with blood vessels. Consecutive sections
      examined for anti-GLUT 1 showed that the protein was distributed in nearly an
      identical pattern to the anti-GFAP, staining fibrillar processes and all vessels
      and also appeared extracellularly. In stab wounds, GLUT 1 immunoexpression was
      similar to GFAP reactivity and stained injured vessels and glial-like processes
      that were reminiscent of astrocytic end-feet. Normal glial cells and processes in
      unaffected neuropil, however, were never stained. This report suggests that GLUT
      1 protein may be upregulated in non-endothelial components, such as reactive
      astroglia or possibly microglia, that are associated with injured or angiogenic
      vessels.

PMID- 7820677
TI  - N-methyl-D-aspartate receptors contribute to afferent synaptic transmission in
      the medial vestibular nucleus of young rats.
AB  - In the medial vestibular nucleus (MVN), the non-N-methyl-D-aspartate (NMDA)
      subtype of ionotropic glutamate receptors has been reported as operating at
      synapses between ipsilateral vestibular afferents and neurons. In the present
      study, we addressed the question of whether or not NMDA receptors contribute to
      afferent synaptic transmission in the MVN and if so, to what degree. Using
      nystatin-perforated or conventional whole-cell patch clamp methods in brainstem
      slices of young rats (postnatal day 4-6), we found that NMDA receptors contribute
      to a substantial extent to afferent synaptic transmission in the MVN of young
      rats.

PMID- 7820676
TI  - Induction of c-fos-like protein in the spinoparabrachial tract-neurons locating
      within the sacral parasympathetic nucleus in the rat.
AB  - Immunoreactivity against c-fos-like protein (FOS) was induced in many neuronal
      cell bodies within the sacral parasympathetic nucleus (SPN) in urethane
      anesthetized rats by chemical irritation of the urinary bladder with formalin.
      More than half of these FOS-immunoreactive neurons were retrogradely labeled with
      Fluoro-Gold injected into the lateral parabrachial nucleus (PBN1). The results
      indicate that some neurons within the SPN may transmit noxious information from
      the urinary bladder to the PBN1.

PMID- 7820678
TI  - Immunohistochemical localization of the neuron-specific glucose transporter
      (GLUT3) to neuropil in adult rat brain.
AB  - The precise histologic localization of GLUT3, a glucose transporter thought to be
      restricted to neurons, is unknown. Using a high-affinity, specific antiserum
      against rodent GLUT3 for immunocytochemistry, light microscopic staining
      concentrates heterogeneously in the neuropil in a region- and lamina-specific
      manner; intense staining characterizes areas with high rates of glucose
      utilization such as inferior colliculus and pyriform cortex. Neuropil
      localization with little perikaryal staining suggests that GLUT3 may provide the
      energy needed locally for synaptic transmission.

PMID- 7820679
TI  - IT15 gene expression in fetal human brain.
AB  - To examine the expression of the gene which causes Huntington's disease (HD),
      IT15, during development, in situ hybridization of radiolabeled riboprobes was
      performed in human fetal (gestational ages 20-23 weeks) and adult brain. Optical
      densities of autoradiographs were determined in various brain regions and
      compared to cell density in those regions. IT15 expression was found in all
      regions of the fetal and adult brain, and there was a high degree of correlation
      of autoradiographic signal with cell number in all regions but germinal matrix in
      fetal brain and white matter in adult brain. These two regions are notable for
      their significant proportion of glial cells, and suggest that IT15 expression is
      predominantly neuronal. There was no preponderance of IT15 expression in striatal
      compartments in fetal brain as demonstrated by acetylcholinesterase activity, nor
      was there differential expression of IT15 in brain regions known to be
      particularly affected in HD. IT15 gene expression is present by 20 weeks
      gestation in human brain, and at that stage of development exhibits a pattern of
      distribution which is similar to adult brain. If a developmentally-regulated role
      for IT15 exists in the pathogenesis of HD, it must occur prior to 20 weeks
      gestation.

PMID- 7820680
TI  - Developmental changes of protein substrates of Ca2+/calmodulin-dependent protein
      kinase II in the rat forebrain.
AB  - We previously reported that the level of Ca2+/calmodulin-dependent protein kinase
      II (CaM kinase II) alpha and beta proteins increases with postnatal age. In the
      present study, we investigated the developmental changes in whole protein
      substrates of CaM kinase II as compared with those of cAMP-dependent protein
      kinase (A-kinase) in the rat forebrain. Protein substrates were phosphorylated
      with [gamma-33P]ATP, and analysed by two-dimensional gel electrophoresis. More
      than 50 substrates for CaM kinase II were found in the soluble and particulate
      fractions. The phosphorylation level of more than 15 substrates increased in the
      particulate fraction during development. Similarly, that of more than 3
      substrates increased in the soluble fraction. Some substrates for A-kinase also
      increased during development, although some decreased. These findings suggest
      that the expression of some substrates is regulated during development and that
      the phosphorylation reaction involves the regulation of neuronal development.

PMID- 7820681
TI  - Threshold and chromatic sensitivity changes in fish cone horizontal cells
      following prolonged darkness.
AB  - The light-evoked responses of L-type cone horizontal cells in the teleost retina
      were studied following a prolonged period of complete darkness. Intact, isolated
      white perch retinas were superfused in complete darkness for more than 90 min,
      following which horizontal cells were impaled without the aid of any light
      flashes. Following this prolonged darkness, L-type cone horizontal cell light
      responses to dim and bright full-field stimuli were slow and small in amplitude
      and response duration to bright stimuli was considerably longer than stimulus
      duration. In addition, absolute threshold was 2 log units lower than typical for
      cone horizontal cells and spectral sensitivity to shorter wavelengths was
      increased. Following bright light stimulation, light responses became more
      transient and increased in amplitude, reaching 40-50 mV to bright flashes.
      Moreover, absolute threshold increased and responses to spectral stimuli were
      similar to those observed typically for L-type cone horizontal cells after light
      sensitization. These results suggest that following prolonged darkness, cone
      input to cone horizontal cells is reduced and rod input is present.

PMID- 7820682
TI  - Glutamate-induced overexpression of NMDA receptor messenger RNAs and protein
      triggered by activation of AMPA/kainate receptors in rat hippocampus following
      forebrain ischemia.
AB  - Severe forebrain ischemia induces a large increase in expression of NMDA receptor
      subunits in rat brain. One week after ischemia, levels of NMDA-R1 mRNAs in the
      CA1 pyramidal cells of hippocampus are 7 times higher than those observed in
      control rats. At 7 days postischemia, an enhanced immunostaining of the NMDA-R1
      subunit was observed in all hippocampal structures indicating that changes in
      mRNA levels are accompanied by changes in receptor protein level. Riluzole, a
      potent inhibitor of glutamate release and CNQX, a selective AMPA/kainate
      antagonist, drastically reduced the ischemia-induced expression of mRNAs for the
      three NMDA receptor subunits while D-AP5, a selective NMDA antagonist, had
      essentially no effect. Therefore ischemia-induced expression of NMDA receptor
      subunits is associated with glutamate release and proceeds via an AMPA/kainate
      pathway. These results together with those of other groups concerning ischemia
      effects on AMPA and GABAA receptor levels, suggest an important role of the
      induced expression of NMDA receptor subunits in the deleterious effects of
      ischemia.

PMID- 7820683
TI  - Selective suppression of intrinsic but not afferent fiber synaptic transmission
      by baclofen in the piriform (olfactory) cortex.
AB  - The GABAB agonist baclofen has been shown to suppress synaptic transmission in
      subregions of the hippocampus and in the piriform (olfactory) cortex. Here we
      report a laminar selectivity of suppression of synaptic potentials in the
      olfactory cortex. In brain slice preparations, baclofen suppresses
      extracellularly recorded field potentials at the intrinsic fiber synapses
      proximal to the superficial pyramidal cell bodies (layer Ib) while leaving the
      afferent fiber synaptic potentials recorded at the distal dendrites (layer Ia)
      little affected. This dose-dependent selective suppression of intrinsic fiber
      synaptic transmission is also correlated with an increase of paired-pulse
      facilitation. These results suggest that afferent and intrinsic synaptic inputs
      may be differentially modulated by the activation of GABAB receptors and that
      this selective suppression is at least partially mediated via a presynaptic
      mechanism.

PMID- 7820684
TI  - Diazepam attenuates hyperexcitability and mechanical hypersensitivity of dorsal
      horn convergent neurones during reperfusion of the rat's tail following
      ischaemia.
AB  - We have investigated the involvement of the GABAA-benzodiazepine receptor complex
      in nociceptive activity of convergent neurones in the spinal cord during
      ischaemia and reperfusion of their receptive fields on the rat's tail. In
      enflurane anaesthetized rats, extracellular recordings were made from convergent
      neurones located throughout the dorsal horn before, during and after 30 min of
      ischaemia. Following intrathecal saline pretreatment, there was a significant
      increase in spontaneous firing rate during ischaemia (219 +/- 21%, P < 0.02, n =
      10) which persisted during reperfusion. After 10 min of reperfusion, the neurones
      exhibited a greater response than before ischaemia to both innocuous brush (54 +/
      11%, P < 0.05, n = 10) and noxious pinch (72 +/- 14%, P < 0.02, n = 10) and the
      enhanced sensitivity persisted over the 60-min reperfusion period. During
      reperfusion, receptive field size increased in most neurones tested. Intrathecal
      diazepam (100 and 500 micrograms) abolished the hyperexcitability and the
      hypersensitivity to both innocuous and noxious mechanical stimulation during
      reperfusion. The highest dose of diazepam (500 micrograms) also attenuated the
      increase in spontaneous firing rate during ischaemia. Diazepam, at the doses
      tested, had no effect on receptive field enlargements during reperfusion. The
      effect of 100 micrograms of diazepam was partially reversed by flumazenil (1
      mg/kg i.p.) but not by naloxone (1 mg/kg i.p.). In the absence of ischaemia,
      diazepam had no effect on spontaneous firing rate nor on the responses to
      innocuous or noxious mechanical stimulation. Our results support an
      antinociceptive role for benzodiazepines in the dorsal horn elements responsible
      for reperfusion hyperalgesia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7820685
TI  - Metabolism-dependent binding of the heterocyclic amine Trp-P-1 in endothelial
      cells of choroid plexus and in large cerebral veins of cytochrome P450-induced
      mice.
AB  - Trp-P-1 (3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole) is known to be metabolized
      by cytochrome P4501A (P4501A) to reactive intermediates which may bind
      irreversibly to tissue macromolecules. The irreversible binding of [3H]Trp-P-1 in
      the brain of NMRI-mice was studied by microautoradiography. There was a selective
      irreversible binding of radioactivity in endothelial cells following an i.v. or
      i.p. injection of [3H]Trp-P-1 (100 micrograms/kg or 1.5 mg/kg) in mice treated
      with the P4501A-inducing agent beta-naphthoflavone (BNF). The binding of
      radioactivity was highest in capillary loops of the choroid plexus, less marked
      in large cerebral veins and in arachnoidal veins whereas no binding was observed
      in cerebral capillaries, arteries, neurons or in other brain cells. In
      endothelial cells of vehicle-treated control mice injected with [3H]Trp-P-1 no
      binding of radioactivity was observed. At incubation of brain slices with [3H]Trp
      P-1, there was a marked irreversible binding of radioactivity in endothelial
      cells in the choroid plexus of BNF-treated mice but not in vehicle-treated
      control mice. The P4501A inhibitor ellipticine abolished the BNF-induced
      endothelial binding of [3H]Trp-P-1-derived radioactivity in vivo and in vitro.
      The marked binding of Trp-P-1-derived radioactivity in endothelial cells of the
      choroid plexus of BNF-treated mice demonstrate that a BNF-responsive enzyme
      activity, possibly P4501A, may be induced at this site and suggests that a P450
      dependent enzyme activity be part of the blood-cerebrospinal fluid barrier
      regulating the transendothelial passage of compounds.

PMID- 7820686
TI  - Histochemical and scanning electron microscopic studies of supernumerary hair
      cells in embryonic rat cochlea in vitro.
AB  - In the embryonic organ of Corti supernumerary hair cells were observed when
      developed in organotypic cultures. Hair cells ranging in up to two rows of inner
      hair cells (IHCs) and up to nine rows of outer hair cells (OHCs), were observed
      by phalloidin histochemistry. The total number of hair cells may double in some
      explanted cochleae compared to control ones. Cuticular plates of hair cells
      displayed an actin-free zone corresponding to the kinocilium location,
      differently located and indicating different degrees of differentiation and
      maturation. Moreover, some hair cells had a small apical surface area and a
      centrally located kinocilium, revealing immaturity. Under scanning electron
      microscopy, stereocilia appeared to differentiate normally, as compared to the in
      vivo development. The staircase pattern of the stereociliary bundles was reached
      on most of the hair cells with a 'V' shape on the OHCs and hemispherical one on
      the IHCs. Hair cell polarity was not homogeneous along the length of the tissue.
      Organs of Corti explanted at birth developed a weaker number of supernumerary
      hair cells showing a decrease of supernumerary hair cells with the developmental
      stage of the explant. These results provide evidence for supernumerary hair cells
      in the mammalian cochlea in culture, without loss or injury to preexisting hair
      cells.

PMID- 7820687
TI  - Bilateral intranigral NMDA blockade increases status duration and neuronal injury
      from systemic kainic acid.
AB  - Limbic seizures may be under the regulation of the substantia nigra, pars
      reticulata (SNpr). Using microinjection of the NMDA antagonist AP7, we
      investigated the role of SNpr in modulating seizures induced by kainic acid.
      Seizure severity was analyzed electrographically and neural injury assessed by
      measurement of heat shock protein (HSP) expression and acid fuchsin (AF) staining
      of vulnerable hippocampal cells. Intranigral injection of AP-7 increased the
      duration of electrographic seizure discharges and the number of HSP-positive and
      acid fuchsin stained cells in all hippocampal sectors, suggesting that blockade
      of the NMDA receptors in SNpr enhanced neural injury.

PMID- 7820688
TI  - Corticotropin-releasing factor mRNA increases in the inferior olivary complex
      during harmaline-induced tremor.
AB  - This study reports that corticotropin-releasing factor (CRF) expression within
      the inferior olivary complex (IOC) of the cat is increased 8 h after
      administration of the tremor-inducing beta-carboline harmaline. Following
      harmaline treatment, hybridization of an oligodeoxynucleotide complementary to
      CRF mRNA increased significantly in the dorsal accessory olive, subnuclei A and C
      of the medial accessory olive and the dorsal cap of Kooy, a subnucleus thought
      previously to be unresponsive physiologically to harmaline. At this early time
      point, greater increases in CRF mRNA hybridization were present in the caudal
      than the rostral IOC. These results support published reports that harmaline
      mediated effects are more profound within the caudal than the rostral IOC, but
      also suggest that harmaline mediates cellular responses in inferior olivary
      neurons which are not related to activation of rhythmic firing.

PMID- 7820689
TI  - Evaluation of the functional connectivity in the nervous system using time
      dependent scatter diagrams.
AB  - We investigated spike trains of the feline nervous system, which are considered
      to be non-stationary point processes characterized by changes of the functional
      interneuronal connectivities. Ordinary long-term averaged correlation methods are
      useful as processing time series data as a quasi-stationary point process, but
      not as a non-stationary point process. We depicted the joint impulse
      configuration scatter diagram proposed by D. H. Perkel et al. for subsets of the
      neural spike-train to find changes of functional connectivities. The time
      dependent scatter diagram was generated by arranging these scatter diagrams in
      chronological order. Time-dependent scatter diagrams were generated for spike
      trains derived from the anterior ectosylvius sulcus, the coronal sulcus, the
      lateral bank of the presylvius sulcus, the medial wall of the presylvius sulcus,
      and the medial wall of the cruciate sulcus. The patterns of time-dependent
      scatter diagrams for these cortices are considered to change in relation to eye
      movement. Changes of these patterns correspond to those of the functional
      connectivities related to the dynamics of eye movement in the neural system.

PMID- 7820690
TI  - Synaptic connections between pars compacta and pars reticulata neurones:
      electrophysiological evidence for functional modules within the substantia nigra.
AB  - Intracellular recordings were performed in vitro from both pars compacta and pars
      reticulata neurones of the substantia nigra, and their postsynaptic responses to
      electrical stimulation within the nucleus were analysed. Intracellular staining
      by biocytin was used to reveal the morphology and location of the recorded
      neurone and its position and distance to the stimulating electrode. Inhibitory
      postsynaptic potentials in pars compacta neurones were evoked exclusively from a
      specific region of stimulation within the pars reticulata; this field could be
      mapped out as a cone-shaped region surrounding the apical dendrite of the cell
      and perpendicular to the plane of the pars compacta. Furthermore,
      hemitransection, prior to the experiments which eliminated the most likely source
      of extrinsic inhibition (the GABAergic striatonigral pathway) affected neither
      the generation of inhibitory postsynaptic potentials nor its topographic pattern
      during pars reticulata stimulation. In contrast to the response of dopaminergic
      pars compacta neurones, pars reticulata neurones responded to stimulation over
      wide areas of substantia nigra, without any clear site-specific selectivity. It
      is concluded that within the substantia nigra, dopaminergic neurones are arranged
      in functional modules such that most inhibition is derived from a highly local
      circuit with the collaterals of adjacent pars reticulata cells. This module is
      intrinsic to the substantia nigra and may represent the basic functional unit of
      the nucleus.

PMID- 7820691
TI  - Parvalbumin expression reveals a vibrissa-related pattern in rabbit SI cortex.
AB  - The expression of parvalbumin-like immunoreactivity (PV-LIR) was examined in the
      mystacial representation within the primary somatosensory cortex (SI) of
      postnatal day 21 and adult rabbits. PV-LIR was expressed in a prominent vibrissa
      like array of patches in layer IV despite the fact that barrels were indistinct
      in the cytoarchitecture. Each patch consisted of dense terminal-like PV-LIR and a
      preferential concentration of intensely labeled stellate neurons. Layer V
      contained scattered small and large intensely labeled basket cells. Layer Vb had
      a distinct layer of lightly labeled large pyramidal cells that received labeled
      basket cell terminations. Upper layer VI also contained patches of terminal-like
      PV-LIR that were in register with the overlying vibrissae pattern. These patches
      also contained a preferential distribution of labeled non-pyramidal cells as well
      as modified pyramidal cells. These results suggest that PV-LIR in rabbits
      delineates cortical modules composed of thalamocortical afferents and inhibitory
      local circuits in the absence of a distinct barrel cytoarchitecture. In contrast,
      prior studies of rat SI cortex have revealed a distinct barrel cytoarchitecture
      but a uniform distribution of PV-LIR. The differences in PV-LIR between rodents
      and lagomorphs within the vibrissae representation in SI may be related to
      species differences in thalamic and local cortical circuits devoted to the
      whisker sense.

PMID- 7820692
TI  - Inferior colliculus neuronal membrane and synaptic properties in genetically
      epilepsy-prone rats.
AB  - Previous studies using single-unit recording techniques have shown that the
      inferior colliculus is critical for audiogenic seizure initiation in genetically
      epilepsy-prone rats (GEPR). In order to investigate cellular abnormalities that
      may be important in causing audiogenic seizure susceptibility, intracellular
      recordings were made from neurons of inferior colliculus dorsal cortex (ICd) in a
      GEPR variety that exhibits severe audiogenic seizures (GEPR-9). GEPR neuronal
      membrane and synaptic properties were compared to those of normal Sprague-Dawley
      rats (SD), the strain from which GEPR were derived. We found six
      electrophysiological differences between GEPR and normal SD ICd neurons, all of
      which could promote seizures in GEPR. (1) Input resistance was higher in GEPR
      than in normal ICd neurons. (2) Threshold for repetitive action potential firing
      was closer to resting membrane potential in GEPR ICd neurons. (3) GEPR neurons
      showed faster repetitive spike firing than normal SD neurons. (4) Anode break
      spikes occurred at the offset of a hyperpolarizing pulse more often in GEPR than
      in normal SD neurons. (5) Stimulation of the commissure of the inferior
      colliculus caused synaptic paired pulse inhibition in normal ICd neurons, but
      paired pulse facilitation was always observed in GEPR neurons. (6) In GEPR, a
      large epileptiform depolarizing event could be elicited by strong electrical
      stimulation of the commissure of the inferior colliculus. In normal SD rats,
      similar epileptiform activity was seen only after application of bicuculline or
      NMDA. Our results suggest that both abnormal neuronal membrane properties and
      altered synaptic transmission are likely to contribute to seizure predisposition
      and audiogenic seizure initiation in GEPR.

PMID- 7820693
TI  - Activation of protein kinase C in the hypothalamic ventromedial nucleus or the
      midbrain central gray facilitates lordosis.
AB  - Many neurotransmitters and neuropeptides can act through the hypothalamic
      ventromedial nucleus (VMN) or midbrain central gray (MCG) to facilitate lordosis.
      Since these lordosis-facilitating agents can also stimulate the phosphoinositide
      (PI) second-messenger pathway, it was hypothesized that direct activation of this
      pathway can also potentiate the behavior. To evaluate this possibility, a phorbol
      ester, TPA (12-O-tetradecanoyl phorbol 13-acetate), was used to activate a key
      enzyme, protein kinase C (PKC), of the PI pathway in ovariectomized (OVX) rats
      either primed or not primed with estrogen. These female rats were paired with
      males for mating tests before and after an intracerebral infusion of TPA, and
      both the lordosis quotient (LQ) and the lordosis strength (LS) were measured.
      Bilateral infusion of TPA (5 micrograms/0.5 microliter or 0.2 microgram/0.2
      microliter, but not 0.1 microgram/0.2 microliter/side) into the VMN or MCG of
      estrogen-primed subjects facilitated both LQ and LS in 30 min, peaked at 60-90
      min, and the facilitation lasted for more than 180 min. This facilitatory effect
      of TPA was: (1) not observed in OVX rats not primed with estrogen; (2) not
      observed if the infused TPA did not reach both sides of the VMN or MCG; (3) not
      mimicked by 4 alpha-phorbol 12,13-didecanoate, which does not activate PKC; (4)
      blocked by PKC inhibitors (H7 10 mM or staurosporine 1 microM, 0.2
      microliter/side), which by themselves did not facilitate lordosis; and (5) was
      not affected by pretreatment of the progestin antagonist RU486.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7820694
TI  - Intranigral but not intrastriatal microinjection of the NMDA antagonist MK-801
      induces contralateral circling in the 6-OHDA rat model.
AB  - When systemically administered to unilaterally 6-OHDA lesioned rats, the non
      competitive antagonist of N-methyl-D-aspartate (NMDA) receptors MK-801 ((+)-5
      methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine) produces a marked
      rotation response toward the lesioned side. In addition, the same type of
      injection in non-denervated rats increases locomotor activity without direction
      predominance. These findings suggest that MK-801 interacts with the dopaminergic
      pathway to induce motor activity. However, intracerebral injection of MK-801 (5
      micrograms/0.5 microliter) in the substantia nigra pars reticulata (SNr), either
      on the lesioned side or the intact side, induces a significant circling response,
      contraversive to the injection side. A similar injection of MK-801 (5
      micrograms/1.0 microliter) in the striatum causes no rotation response. These
      results show that the non-competitive NMDA antagonist can induce motor activity
      in the presence or in the absence of the dopaminergic pathway and that in the
      latter case its action is exerted predominantly at the level of the substantia
      nigra, perhaps through suppression of the excitatory subthalamic drive.

PMID- 7820695
TI  - Reversal of hemorrhagic shock in rats by oxotremorine: the role of muscarinic and
      nicotinic receptors, and AV3V region.
AB  - In an experimental model of hemorrhagic shock resulting in the death of almost
      all rats within 20-30 min, centrally active cholinomimetic drugs are reported to
      induce a prompt, sustained and dose-dependent improvement in blood pressure and
      survival rate claimed to be due to nicotinic, but not muscarinic actions. In the
      present study, cholinergic receptor agonist, oxotremorine (50 micrograms/kg,
      i.v.) increased mean arterial pressure (from 22 +/- 1 to 123 +/- 3 mm Hg) and 60
      min-survival rate (from 0% to 92%) in rats bled to hypovolemic shock. Atropine (2
      mg/kg, i.v.) pretreatment inhibited the pressor effect of oxotremorine
      significantly, but did not modify its effect on survival rate. On the other hand,
      pretreatment with mecamylamine (50 micrograms, i.c.v.) almost abolished the
      reduction in mortality rate, but inhibited the pressor effect of oxotremorine,
      partially. These results indicate that oxotremorine-induced pressor response and
      decrease in mortality in rats with severe hemorrhagic shock are primarily
      mediated via central muscarinic and nicotinic receptors, respectively. AV3V
      region was previously reported to be involved in pressor and natriuretic effects
      of i.c.v. carbachol in normotensive rats. In the present study, the electrolytic
      lesions of AV3V region significantly inhibited oxotremorine-induced increases in
      both blood pressure and survival rate in rats subjected to hemorrhagic shock.
      These findings indicate that AV3V region plays a major role in cholinergic
      cardiovascular control in hypotensive animals as well as normotensives.

PMID- 7820696
TI  - Pharmacology of the GABAB receptor in amphibian retina.
AB  - Amacrine and ganglion cells in the amphibian retina contain GABAB, as well as
      GABAA, receptors. Baclofen, a GABAB agonist, hyperpolarizes the dark membrane
      potential of these third order neurons and makes their light responses more
      transient. GABAB receptors in the retina have a similar agonist profile to GABAB
      receptors described at other sites in the brain. Namely, preferential activation
      by the R-enantiomer of baclofen, and agonist sensitivity in the order 3
      aminopropylphosphinic acid > baclofen >> 3-aminopropylphosphonic acid. The GABAB
      receptor was not activated by 4-aminobutylphosphonic acid. Several antagonists,
      such as phaclofen, saclofen, and 2-hydroxysaclofen, were ineffective in the
      amphibian retina. However, CGP35348 blocked the action of applied baclofen and
      produced effects on the light response that were opposite to those of baclofen.
      Applied agonists and antagonists support the hypothesis that GABAB receptors
      serve to regulate the balance of sustained and transient signals to the inner
      retina.

PMID- 7820697
TI  - Ammonia stimulates the release of taurine from cultured astrocytes.
AB  - The effect of ammonia on the release of the neuroactive amino acids taurine
      (TAU), gamma-aminobutyric acid (GABA) and D-aspartate (D-ASP), an analog of L
      glutamate (L-GLU), from cultured rat cortical astrocytes was studied. NH4Cl (1
      and 5 mM) induced the release of TAU. TAU release was reduced when Na+ was
      removed, and was almost completely abolished when Cl- was omitted. In contrast,
      TAU basal release was enhanced upon removal of Na+ or Cl-. Ammonia inhibited the
      release of GABA and D-ASP. Ammonia-induced release of astroglial TAU may modify
      the neuronal excitability accompanying hyperammonemic conditions.

PMID- 7820698
TI  - Lesions of the thalamic intergeniculate leaflet block activity-induced phase
      shifts in the circadian activity rhythm of the golden hamster.
AB  - A variety of stimuli, which are associated with acute increases in locomotor
      activity, induce similar phase-dependent shifts in the circadian rhythm of
      locomotor activity in golden hamsters. Treatment with the benzodiazepine,
      triazolam (Tz), or transfer of an animal normally housed without a running wheel
      to a new cage with 1 h of access to a wheel are both examples of such stimuli.
      Phase shifts normally induced by injections of Tz can be blocked by lesions of
      the intergeniculate leaflet (IGL) of the thalamus. Experiments were conducted to
      determine whether phase shifts induced by transfer to a new cage with a running
      wheel also require an intact IGL. Animals normally housed without running wheels
      were transferred to new cages with access to wheels for 1 h a few hours before
      the expected onset of activity. They then received either lesions of the IGL or
      sham lesions and, after recovery, they were again transferred to new cages with
      running wheels for 1 h. Lesions of the IGL blocked phase shifts normally induced
      by wheel access while sham lesions had no effect. The amount of wheel-running and
      total locomotor activity which occurred during access to the running wheel were
      significantly reduced by IGL lesions. These results indicate that the phase
      shifting effect of a novel running wheel depends upon an intact IGL.

PMID- 7820700
TI  - Neurochemical evidence that AMPA receptor-mediated tonic inhibition of
      hypothalamic dopaminergic neurons occurs via activation of inhibitory
      interneurons.
AB  - Blockade of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)
      receptors with 6-nitro-7-sulfamoyl-benzo-[f]quinoxaline-2,3(1H,4H)-dione (NBQX)
      activates tuberoinfundibular (TIDA) and periventricular-hypophysial dopaminergic
      (PHDA) neurons suggesting that these neurons are tonically inhibited by
      endogenous excitatory amino acid neurotransmitters acting at AMPA receptors. The
      purpose of the present study was to identify prospective inhibitory
      neurotransmitters mediating this effect by examining the ability of gamma
      aminobutyric acid (GABA)A and kappa-opioid receptor agonists to reverse the
      stimulatory effects of NBQX on the activity of these neurons (estimated from
      concentrations of 3,4-dihydroxyphenylacetic acid [DOPAC] in the median eminence
      and intermediate lobe of the pituitary). The GABAA receptor agonist isoguvacine
      prevented the NBQX-induced increase in DOPAC concentrations in the median
      eminence but not in the intermediate lobe. The kappa-opioid receptor agonist U
      50,488 had no effect in the median eminence, but attenuated the NBQX-induced
      increase of DOPAC concentrations in the intermediate lobe. These results suggest
      that excitatory amino acid neurotransmitters activate AMPA receptors and increase
      release of GABA, which by acting at GABAA receptors tonically inhibits TIDA
      neurons. On the other hand, AMPA receptor-mediated tonic inhibition of PHDA
      neurons occurs, at least in part, by a mechanism involving endogenous kappa
      opioids.

PMID- 7820699
TI  - Increase of prolactin mRNA in the rat hypothalamus after intracerebroventricular
      injection of VIP or PACAP.
AB  - Vasoactive intestinal peptide (VIP), the structurally homologous pituitary
      adenylate cyclase-activating peptide (PACAP) and the pituitary hormone, prolactin
      (PRL) enhance rapid eye movement sleep (REMS). VIP and PACAP are both inducers of
      PRL gene expression and release in the pituitary gland. Little is known about PRL
      regulation in the brain although it is hypothesized that the REMS-promoting
      activity of i.c.v. administered VIP may be mediated via the activation of
      cerebral PRL. To test whether VIP or PACAP in fact increase intracerebral mRNA,
      the peptides (VIP: 30 or 300 pmol; PACAP: 220 pmol) were injected i.c.v. into
      rats at dark onset. 1 h later, cDNA was synthesized from purified hypothalamic
      mRNA. Standardized amounts were analysed for PRL using the polymerase chain
      reaction followed by Southern blotting and hybridization. Compared with beta
      actin mRNA levels, both VIP and PACAP increased PRL mRNA levels in a dose
      dependent fashion though VIP was more effective on a molar basis. The previously
      reported alternatively spliced PRL mRNA (lacking exon 4) was not detected. The
      data support the hypothesis that the REMS-promoting activity of central VIP and
      PACAP might be mediated by cerebral PRL.

PMID- 7820701
TI  - Purine- and pyrimidine-stimulated phosphoinositide breakdown and intracellular
      calcium mobilisation in astrocytes.
AB  - Phosphoinositide breakdown in cultured cortical astrocytes was assessed by
      measuring the accumulation of [3H]inositol phosphates (IP's) following
      incubations with various purines and pyrimidines. Dose-response relationships
      gave the following order of potency: 2-methylthioadenosine triphosphate (2
      MeSATP) > uridine 5'-triphosphate (UTP) > ATP = ADP > inosine 5' triphosphate
      (ITP). However, 2-MeSATP and UTP were only half as effective as either ATP or ADP
      in stimulating [3H]IP production. Astrocytes were also challenged with combined
      additions of maximally effective concentrations of agonists. Responses to ADP
      plus UTP and 2-MeSATP plus UTP were essentially additive whilst ATP plus UTP
      evoked a response which was only partially additive. ATP-stimulated [3H]IP
      accumulation was markedly reduced in the presence of 2-MeSATP suggesting that the
      latter may be a partial agonist at these receptors. We also examined the ability
      of ATP and UTP to increase intracellular Ca2+ concentrations in these cells.
      Greater than 90% of all cells tested responded to ATP with a release from
      internal Ca2+ stores but less than half of these responded similarly when
      challenged with UTP. Our results indicate that astrocytes possess both P2Y
      purinoceptors and a population of receptors which are also coupled to
      phosphoinositide metabolism and intracellular Ca2+ mobilisation but recognise ATP
      and the pyrimidine nucleotide UTP.

PMID- 7820702
TI  - The effects of chronic treatment with N-tert-butyl-alpha-phenylnitrone on
      cerebellar noradrenergic receptor function in aged F344 rats.
AB  - We examined if a 2 week treatment with the spin trapping agent N-tert-butyl-alpha
      phenylnitrone (PBN) would alleviate age-related deficits in cerebellar
      noradrenergic function of male 21-22 month old F344 rats compared to age-matched
      controls. Noradrenergic receptor function of PBN-treated rats was similar to
      young rats whereas for non-treated rats it was typical of that previously
      recorded in aged rats. Thus, treatment with PBN may reverse age-related deficits
      in cerebellar noradrenergic receptor function.

PMID- 7820703
TI  - Effects of systemic or oral ad libitum monosodium glutamate administration on
      striatal glutamate release, as measured using microdialysis in freely moving
      rats.
AB  - We examined effects of high doses of monosodium glutamate (MSG) on extracellular
      glutamate levels in rat striata, using in vivo microdialysis. Parenteral doses
      (0.5, 1.0 and 2.0, but not 0.25, g/kg, i.p.) caused dose- and time-dependent
      increases, peaking after 40 min (at 174 +/- 47%, 485 +/- 99% and 1021 +/- 301% of
      basal levels, respectively). In contrast, dietary MSG (1.49 +/- 0.10 g/kg/h) was
      ineffective.

PMID- 7820704
TI  - Separation of hippocampal theta dipoles by partial coherence analysis in the rat.
AB  - In order to separate the effect of different theta generators in the hippocampus
      and to characterize the pattern of relationships between them, in this study, we
      calculated the coherence that remains between EEG signals, recorded (1) in the
      stratum oriens of the CA1 region and (2) close to the hippocampal fissure in the
      dentate gyrus of the right or left hippocampus, after the variations, common also
      for a third recording site is eliminated (partialization). We found that in both
      anesthetized and freely moving rats, there is a selective high correlation
      (coherence) between theta rhythmic activities of contralateral homonymous sites
      of the hippocampus. The coherence between field potentials recorded in
      ipsilateral superficial and deep layers was eliminated when allowance was made
      for any of the contralateral hippocampal recordings. On the other hand, coherence
      between contralateral homonymous theta dipoles did not decrease when partialized
      by a heteronymous hippocampal EEG signal. The present results support earlier
      findings on multiple hippocampal theta dipoles and indicate that they can be
      separated using partial coherence analysis. The left and right superficial and
      deep dipoles oscillate as if they formed two separate systems one extending over
      the superficial CA1 layers on both sides and the other consisting of the left and
      right deep hippocampal theta dipoles. The results also suggest an important role
      of the commissural projections in interhemispheric theta synchronization.

PMID- 7820705
TI  - Regulation of peripheral-type benzodiazepine receptors in cultured astrocytes by
      monoamine and amino acid neurotransmitters.
AB  - Exposure of primary cultured astrocytes for 3 days to 1 microM of either
      dopamine, serotonin or norepinephrine resulted in upregulation (25-34% increase
      in Bmax) of the peripheral-type benzodiazepine receptors (PBRs) labeled with
      [3H]Ro5-4864. A similar treatment with gamma-aminobutyric acid [GABA] caused a 2
      fold increase in the affinity (Kd) of [3H]Ro5-4864. The monoamines tested and
      GABA had no effect on the binding parameters of [3H]PK 11195, another selective
      PBR ligand. The present study indicates that Ro5-4864 binding sites are
      susceptible to regulation by specific neurotransmitters and provides further
      evidence for the distinction between Ro5-4864 and PK 11195 binding sites of the
      PBRs in cultured astrocytes.

PMID- 7820706
TI  - Whole-cell recordings of spontaneous synaptic currents in medial preoptic neurons
      from rat hypothalamic slices: mediation by amino acid neurotransmitters.
AB  - Whole-cell recordings in hypothalamic slices from immature rats were used to test
      the hypothesis that inhibitory and excitatory amino acid neurotransmitters
      mediate fast synaptic currents in the medial preoptic area (MPOA). Bicuculline
      methiodide reversibly blocked spontaneous inhibitory postsynaptic currents
      (IPSCs), and 6-cyano-2,3-dihydroxy-7-nitroquinoxaline (CNQX) blocked spontaneous
      excitatory postsynaptic currents (EPSCs). These competitive antagonists act at
      gamma-aminobutyric acid (GABA)A and non-N-methyl-D-aspartate (NMDA) glutamate
      receptors, respectively, thus supporting the hypothesis that these amino acid
      receptors activate most if not all fast synaptic currents in the MPOA.

PMID- 7820708
TI  - Computerised determination of spontaneous inspiratory and expiratory times in
      premature neonates during intermittent positive pressure ventilation. I: A new
      technique.
AB  - A pneumatic capsule applied to the sub-xiphisternum provides a signal of
      spontaneous respiratory effort. Purpose-written software analyses this waveform
      to determine spontaneous inspiratory and expiratory times. Algorithms reject
      artefacts. The computerised system allows continuous measurement of spontaneous
      inspiratory and expiratory times to be made during intermittent positive pressure
      ventilation. The accuracy of the system was measured in 17 infants ventilated for
      respiratory distress syndrome: median (range) gestation and birth weight were 31
      (25-38) weeks and 1195 (506-3260) g. The new technique can measure inspiratory
      time of individual breaths with a mean error of 5.4% and expiratory time with a
      mean error of 1.6%.

PMID- 7820707
TI  - Effects of magnesium sulphate and nitric oxide in pulmonary hypertension induced
      by hypoxia in newborn piglets.
AB  - AIM: To examine the haemodynamic effects of intravenous magnesium sulphate on an
      animal model of neonatal pulmonary hypertension induced by hypoxia. METHODS: The
      cardiac index (Q), pulmonary arterial pressure (PAP), systemic arterial pressure
      (SAP), and pulmonary (PVRI) and systemic (SVRI) vascular resistance indices were
      measured in nine newborn piglets (including three controls). Pulmonary
      hypertension was induced by lowering the FIO2 to 0.12-0.14, after which there was
      a significant increase in PAP and PVRI (37% and 142%, respectively; p < 0.01) and
      a significant fall in SAP and Q (30% and 33%, respectively; p < 0.01). RESULTS:
      Magnesium sulphate was infused intravenously as four doses of 25 mg/kg, 15
      minutes apart, which resulted in a significant mean (SD) increase in serum
      magnesium (0.83 (0.07) mmol/l to 1.82 (0.19) mmol/l; p < 0.01). After the initial
      dose SAP, SVRI, PAP and PVRI decreased, but not significantly. Each subsequent
      dose of (50, 75, 100 mg/kg) was accompanied by further significant reductions in
      these variables from control baseline (p < 0.05). The PVRI:SVRI ratio remained
      unchanged throughout. Inhaled nitric oxide (NO) 40 ppm was administered after the
      last dose of magnesium sulphate. The PVRI:SVRI significantly decreased (p <
      0.05), indicating that reversible pulmonary hypertension remained after a maximum
      dose of magnesium sulphate. CONCLUSIONS: Unlike NO, magnesium sulphate is not a
      selective pulmonary vasodilator and may lead to deleterious effects on systemic
      pressures in critically ill newborns.

PMID- 7820709
TI  - Computerised determination of spontaneous inspiratory and expiratory times in
      premature neonates during intermittent positive pressure ventilation. II: Results
      from 20 babies.
AB  - Twenty premature infants ventilated for respiratory distress syndrome (RDS) were
      studied using a new computerised technique to determine spontaneous inspiratory
      and expiratory times. The technique is continuous and non-invasive. Infants were
      studied during intermittent positive pressure ventilation for periods of up to 45
      minutes. Median birth weight and gestation were 1477 g and 30 weeks. The median
      number of breaths analysed for each baby was 925. The median (range) for
      spontaneous inspiratory time was 0.30 (0.26 to 0.34) seconds and for spontaneous
      expiratory time it was 0.46 (0.34 to 0.66) seconds. The spontaneous inspiratory
      and expiratory times were different from the ventilator settings.

PMID- 7820710
TI  - Comparison of surface properties and physiological effects of a synthetic and a
      natural surfactant in preterm rabbits.
AB  - AIMS: To compare the physical and physiological properties of a synthetic
      surfactant (Exosurf, Wellcome Foundation) and a natural surfactant (Curosurf,
      Chiesi Farmaceutici). METHODS: Surface properties of the surfactant suspensions
      (10 mg phospholipid/ml) were evaluated using the pulsating bubble surfactometer.
      Lung-thorax compliance was determined in 47 immature newborn rabbits with a
      gestational age of 27 days, treated with recommended clinical doses of either
      surfactant (Exosurf 67.5 mg/kg; Curosurf 200 mg/kg). The lungs were examined
      histologically. RESULTS: The mean (SD) contractile forces of the surface at
      maximum and minimum bubble size were significantly lower for Curosurf than for
      Exosurf: 31 (2) and 0 (0) mN/m v 53 (5) and 29 (4) mN/m, respectively. Mean (SD)
      lung-thorax compliance after one hour of ventilation was significantly higher in
      rabbits treated with Curosurf compared with animals receiving Exosurf or those
      serving as controls: 0.60 (0.15) ml/cm H2O.kg v 0.44 (0.03) and 0.34 (0.18) ml/cm
      H2O.kg, respectively. Both surfactants increased alveolar volume density compared
      with results for control animals, but only Curosurf significantly reduced the
      incidence of moderate or severe bronchiolar epithelial disruption. CONCLUSIONS:
      The natural surfactant, Curosurf, reduced the contractile force at an air-liquid
      interface to a greater extent than the synthetic surfactant, Exosurf, and led to
      a greater improvement in compliance and less airway epithelial damage when given
      in clinical treatment doses to immature rabbits.

PMID- 7820711
TI  - Prognostic value of the immediate response to surfactant.
AB  - AIM: To evaluate the association between the immediate response to surfactant
      treatment and morbidity and mortality in infants with severe respiratory distress
      syndrome. METHODS: The response to surfactant was defined as the difference in
      the arterial:alveolar (delta a:A) ratio before and one hour after the first
      surfactant dose. Measurements were obtained from 253 Israeli infants
      participating in the multi-centre Curosurf 4 trial of surfactant replacement
      therapy. RESULTS: Delta a:A ratios ranged from -0.115 to 0.8 and were
      significantly related to both birth weight and gestational age. Among infants
      weighing 1001-1500 g mortality decreased from 40% among very bad responders to
      zero among good responders. The incidence of pneumothorax decreased with better
      response. Logistic regression analysis showed a hierarchy of predictive power for
      mortality: birth weight or gestational age; immediate response to surfactant;
      severity of initial disease. CONCLUSION: The immediate response to surfactant
      treatment is a significant prognostic indicator for mortality and morbidity.

PMID- 7820713
TI  - Presentation of obstructive left heart malformations in infancy.
AB  - This study documents the presentation of acutely life threatening congenital
      heart disease in infancy in order to assess the performance of screening
      examinations soon after birth and at 6 weeks of age. All cases of obstructive
      left heart malformations presenting in infancy in one health region from 1987-91
      were analysed retrospectively. Altogether, 120 infants presented with either
      hypoplastic left heart syndrome, interruption of the aortic arch, coarctation of
      the aorta, or aortic valve stenosis. Twelve became symptomatic or died within 24
      hours. Thirty four had an abnormal neonatal examination, eight of whom were
      referred. Six more became symptomatic before discharge. Ninety four babies went
      home, 51 developed heart failure before 6 weeks, and another seven died without
      diagnosis. Twenty five of 36 (69%) reaching 6 weeks without diagnosis had a
      second examination which was abnormal in 17. Two babies died undiagnosed after 6
      weeks and the other 18 presented at up to 11 months of age. The neonatal and 6
      week examinations perform poorly as screening tests for congenital heart disease.
      A normal neonatal examination does not exclude life threatening congenital heart
      disease.

PMID- 7820712
TI  - Instillation rate effects of Exosurf on cerebral and cardiovascular haemodynamics
      in preterm neonates.
AB  - The acute effects of surfactant instillation rate on the cerebral and
      cardiovascular haemodynamics were studied in a randomised trial of 27 preterm
      neonates with respiratory distress syndrome (RDS). Cerebral blood flow velocity
      (CBFV), mean arterial blood pressure (MABP), blood gases and electroencephalogram
      (EEG) were continuously recorded before, during, and for at least 10 minutes
      after the administration of surfactant. The measurements were repeated one,
      three, and six hours later. Left ventricular output (LVO) and ductal patency were
      assessed 10 minutes before and then one, three, and six hours after surfactant
      administration. Surfactant (Exosurf) was instilled rapidly over five minutes in
      13 infants and slowly over 15 minutes in 14 infants. The rapid group showed a
      significant but transient increase (mean 38%) in CBFV, a rise strongly related to
      an increase in carbon dioxide tension. No significant change in CBFV was observed
      in the slow group. There were no significant changes in EEG, MABP, LVO, or ductal
      shunting in either group. The findings suggest that rapid instillation of Exosurf
      leads to an increase in CBFV and partial carbon dioxide pressure (PCO2) and
      requires a close monitoring of blood gases to maintain adequate ventilation.
      Furthermore, the findings should alert clinicians to the need for slow infusion
      of Exosurf.

PMID- 7820714
TI  - Iodine content of infant formulas and iodine intake of premature babies: high
      risk of iodine deficiency.
AB  - As part of a study of thyroid function in premature babies, the iodine content of
      their mothers' breast milk, that of 32 formulas from different brands used in
      Spain, and that of 127 formulas used in other countries was determined. Breast
      milk contained more iodine--mean (SEM) 10 (1) microgram/dl--than most of the
      formulas, especially those for premature babies. Iodine intakes were therefore
      below the recommended daily amount (RDA) for newborns: babies of 27-30 weeks'
      gestational age took 3.1 (1.1) micrograms/day at 5 days of age and 29.8 (2.7)
      micrograms by 2 months of age. This problem is not exclusive to Spanish premature
      babies as the iodine content of many of the formulas on sale in other countries
      was also inadequate. It is concluded that preterm infants who are formula fed are
      at high risk of iodine deficiency.

PMID- 7820715
TI  - IgA antibodies in human milk: epidemiological markers of previous infections?
AB  - The concept of an enteromammary link in secretory IgA (SIgA) antibody production
      was tested by hypothesising that specific SIgA antibody profiles in human milk
      might be an epidemiological marker for enteropathogens in a community. Milk from
      three subject groups was studied: 64 Sri Lankan women living in poor suburbs of
      Colombo, 20 Asian immigrant women domiciled in Birmingham, for a median period of
      five years (range 14 days-16 years), and 75 white women living in Birmingham. An
      enzyme linked immunosorbent assay (ELISA) was developed for the detection and
      measurement of SIgA antibodies to a panel of 14 crude O and 10 pure
      lipopolysaccharide antigens of diarrhoeagenic Escherichia coli strains well known
      to be endemic in the Indian subcontinent. The number of Sri Lankan and Asian
      immigrant women with SIgA antibodies to all 14 diarrhoeagenic E coli antigens
      (except O127 in Asian women) was significantly higher than in the white controls.
      The amount of E coli O antigen specific SIgA antibody activity as a percentage of
      total SIgA also gave significantly higher median values in Sri Lankan (6%) and in
      Asian immigrant (4%) women than in white controls (0.7%). SIgA antibodies were
      highly O serogroup specific and showed excellent concordance between crude O and
      the corresponding purified lipopolysaccharide antigens. These results suggest
      that milk antibody profiles represent an epidemiological marker of exposure to
      enteral pathogens. The continuing specific milk antibody response in Asian women
      who have been domiciled in the United Kingdom for many years may indicate
      'memory' in the human secretory immune system.

PMID- 7820716
TI  - Use of local neural tube defect registers to interpret national trends.
AB  - To conduct a number of studies into the prevalence of neural tube defects (NTD)
      in the area covered by the Oxford Record Linkage Study (ORLS), multiple sources
      were used to build a local register of cases occurring in Oxfordshire and West
      Berkshire between 1968-1990. One source of potential cases--namely, termination
      and congenital malformation monitoring data available for the locality from the
      Office of Population Censuses and Surveys (OPCS) data--were kept separate.
      Comparison of the local cases recorded by OPCS and those known to the register
      from 1974-1990, using the method of capture-recapture, suggested that national
      data are only about two thirds complete, but that this underreporting is likely
      to be reasonably consistent from year to year. OPCS data can therefore be used to
      study NTD trends if not absolute risks. The local register seemed, by the same
      yardstick, to be very complete and is being used in a variety of studies of the
      occurrence of NTD. Survival to one year in this area, over the period 1968-1990,
      has only improved in the recent past, if at all. Most NTD pregnancies now end in
      termination rather than birth, and there has been a true decline in the
      occurrence of NTDs, and likewise the different subtypes.

PMID- 7820717
TI  - Neonatal abstinence syndrome after maternal methadone treatment.
AB  - Thirty two infants born to mothers taking methadone and 32 matched controls were
      studied to determine the incidence, timing, and frequency of persistence of
      withdrawal signs in infants born to maternal methadone users. Twelve (37%)
      infants received treatment for symptoms of withdrawal. The median length of time
      from birth to initiation of treatment was 23 hours (range 15-64 hours), the
      median length of treatment was six days (range 1-22 days). In the first six weeks
      after birth there was no significant difference in minor withdrawal symptoms and
      signs, general practitioner or accident and emergency visits between the group
      who did not receive treatment for withdrawal and the control group. If immediate
      treatment for withdrawal is not required major symptoms do not subsequently occur
      with great frequency. Late withdrawal signs were not seen in this study.

PMID- 7820718
TI  - Heel blood sampling in preterm infants: which technique?
AB  - Preterm infants undergoing heel blood sampling were randomly allocated to
      specimen collection by heel puncture (Autolet II Clinisafe) or incision
      (Tenderfoot 'preemie'). A total of 187 procedures was observed in 47 infants. No
      significant difference was found in the infants' behavioural response, increase
      in heart rate, or in the frequency of specimen haemolysis. Collection times for
      small to medium sized samples were similar, but for large samples (> 1 ml) the
      Tenderfoot method was superior and fewer repeat procedures were necessary.
      Tenderfoot has the added advantage of improved safety, but it is too costly for
      routine use.

PMID- 7820719
TI  - Poor prognosis after prolonged ventilation for bronchopulmonary dysplasia.
AB  - Of 47 babies mechanically ventilated for more than 27 days for bronchopulmonary
      dysplasia 20 eventually died. There were no neurodevelopmentally intact survivors
      among those who were ventilated for more than 50 days. Days of ventilation more
      powerfully predicted outcome than ultrasound evidence of brain injury.

PMID- 7820720
TI  - Umbilical cord ulceration in association with intestinal atresia in a child with
      deletion 13q and Hirschsprung's disease.
AB  - The case is reported of a baby boy with an interstitial deletion of the long arm
      of chromosome 13 who, in addition to the described associations of Hirschsprung's
      disease and intestinal atresia, had umbilical cord ulceration resulting in
      massive intrapartum haemorrhage. This case provides support for the existence of
      a previously reported association between umbilical cord ulceration and
      intestinal atresia, and suggests that it is aetiologically heterogeneous.

PMID- 7820721
TI  - Aerosolised prostacyclin for pulmonary hypertension in neonates.
AB  - Aerosolised prostacyclin (PGI2) was administered to two neonates with pulmonary
      hypertension to dilate the pulmonary vessels selectively. The alveolar-arterial
      oxygen gradient fell from 73.2 (patient 1) and 71.8 kPa (patient 2) to 33.8 and
      26.7 kPa respectively. Systemic blood pressure remained stable while pulmonary
      blood pressure declined in patient 1. When inhaled, PGI2 seems to improve
      oxygenation, mainly due to reduction of intrapulmonary shunting.

PMID- 7820722
TI  - Hydrops fetalis caused by a blood group antibody usually undetected in routine
      screening.
AB  - A case of isoimmunisation in pregnancy caused by antibodies to the Kpa red blood
      cell antigen is described. The preceding pregnancy had resulted in fetal hydrops
      for which no cause was found as the antibody screening cells used to investigate
      the fetal hydrops were Kpa negative. This case emphasises the importance of
      serological screening at a reference laboratory for low frequency red cell
      antigens before a diagnosis of non-immune hydrops is made.

PMID- 7820723
TI  - Withholding and withdrawing life sustaining treatment in neonatal intensive care:
      issues for the 1990s.

PMID- 7820724
TI  - Diabetes in pregnancy.

PMID- 7820725
TI  - Ambroise Pare (1510-1590): surgeon and obstetrician of the Renaissance.

PMID- 7820726
TI  - Fresh frozen plasma and neonatal sepsis.

PMID- 7820727
TI  - Urea and its bioavailability in newborns.

PMID- 7820728
TI  - EMLA and informed consent in neonates.

PMID- 7820729
TI  - Lipid peroxidation as a measure of oxygen free radical damage in the very low
      birthweight infant.

PMID- 7820730
TI  - Assessment of donor cell survival in fresh allografts (ligament, tendon, and
      meniscus) using DNA probe analysis in a goat model.

PMID- 7820732
TI  - Arthroscopic versus open debridement of penetrating knee joint injuries.
AB  - Arthroscopic debridement of penetrating knee joint injuries has become a common
      treatment method. A comparative study was undertaken to compare this method with
      open joint debridement. Fourteen penetrating knee joint injuries (fourteen
      patients) were treated by arthroscopic examination and debridement and were
      compared to sixteen penetrating knee joint injuries (fifteen patients) treated by
      open debridement. There were no resultant infections or operative complications
      in either group. Of note, the arthroscopic debridement group had a shorter
      postoperative hospital stay [mean of 1.6 days compared to a mean of 2.6 days in
      the open debridement group (p < 0.02)], a significant incidence of additional
      intra-articular injuries detected (p < 0.01), less postoperative pain, and a
      superior cosmetic result. We conclude that arthroscopic debridement of
      penetrating knee joint injuries is a safe and effective method of treatment,
      providing additional diagnostic information while minimizing morbidity and
      reducing hospital stay.

PMID- 7820731
TI  - Total quadriceps sparing, endoscopic single-incision anterior cruciate ligament
      reconstruction using fresh frozen allograft tissue: surgical technique and
      potential pitfalls.

PMID- 7820733
TI  - Limb salvage tumor surgery in children.
AB  - Limb salvage tumor surgery in children is quite popular. Low local recurrence
      rates and patient survival statistics prove it is a viable option for many
      patients. We review the major changes in medicine and paramedical fields that
      have allowed limb salvage to develop. We then discuss patient selection, limb
      salvage goals, review the surgical staging system, and examine common errors in
      evaluating a tumor patient. A discussion (with case examples) of various surgical
      options and a brief look at some current trends is then presented.

PMID- 7820734
TI  - A primer of osteotomy of the weight bearing long bones in children.
AB  - A. Why Perform An Osteotomy In Childhood or Adolescence? 1. Progressive deformity
      for which osteotomy is curative. 2. Cosmesis. 3. To prevent the development of
      late osteoarthritis (unproven). 4. Progressive ligamentous laxity (rare). 5.
      Functionally limiting deformities (rare). 6. Development of adaptive joint
      deformity (rare). B. When To Perform An Osteotomy 1. Immediate correction for
      progressive deformities or functionally limiting deformities that can not be
      expected to improve by the natural history of the deformity. 2. Immediate
      correction if the problems listed under "A" are present such as the development
      of adaptive joint deformity or progressive ligamentous laxity. 3. If no
      indication for osteotomy exists except cosmesis, consider delaying correction to
      avoid the need for repeated osteotomies in disorders for which recurrence is
      common. C. How To Do The Osteotomies 1. Perform the osteotomy at the level of the
      deformity when possible. 2. Choose the simplest, safest method that will
      accomplish specific goals. 3. Complex restoration of perfect mechanical axis and
      joint alignment may not be necessary. The lesser risks of simpler techniques
      should be considered. 4. The specific technique chosen will depend on the
      experience and abilities of the treating physician.

PMID- 7820735
TI  - Mechanoreceptor endings in human cervical facet joints.
AB  - Normal cervical facet capsules, taken from three human subjects, were examined to
      determine the density and distribution of three types of mechanoreceptive nerve
      endings. Clearly identifiable mechanoreceptors were found in 80% of the specimens
      and were categorized according to the classification of Freeman and Wyke. Eleven
      Type I, twenty Type II, and five Type III receptors were identified, as well as a
      number of small, unencapsulated nerve endings. Type I receptors were small,
      globular structures measuring 25-50 microns in diameter. Type II receptors varied
      in size and contour, but were characterized by their oblong shape and broad,
      lamellar capsule. Type III receptors were relatively large, oblong structures
      with a thin, amorphous capsule, within which a reticular mesh-work of fine
      neurites was embedded. Free (nociceptive) nerve endings were found in sub
      synovial, loose areolar, and dense capsular tissues. The presence of
      mechanoreceptive and nociceptive nerve endings demonstrates that cervical facet
      capsules are monitored by the central nervous system, and implies that neural
      input from the facets is important to the function of the cervical spine.
      Previous studies have suggested that protective muscular reflexes modulated by
      these types of mechanoreceptors are important in preventing joint instability and
      degeneration. The complex neural elements identified in this study may be damaged
      inadvertently when surgically exposing the cervical spine. Care should be taken,
      during posterior approaches, to avoid excessive stripping of the facets in
      portions of the spine not being fused.

PMID- 7820736
TI  - Effects of variation of cement thickness on bone and cement stress at the tip of
      a femoral implant.
AB  - With the resurgence of the use of bone cement in total hip arthroplasty, a
      renewed concern in techniques or designs that may reduce cement fixation failure
      has arisen. Analysis of the stresses at the tip of the prosthesis may suggest
      strategies to reduce loosening. Using a three-dimensional finite element model
      this study analyzed stresses in the bone, cement, and prosthesis near the tip of
      a femoral component as a function of cement thickness. A section of an idealized
      circular femoral shaft with implant prosthesis and cement was modeled with
      loading conditions representing the stance phase of gait. Increasing cement
      thickness is predicted to significantly reduce stress in the cement mantle of a
      femoral implant. Tensile stress is reduced by fifty percent while shear stress is
      reduced at least twelve percent. Peak tensile stresses occur on the medial side
      at the tip of the prosthesis in a transverse direction, indicating likelihood of
      failure due to debonding. Local shear stress peaks also occur at the tip. Shear
      stresses in the cement mantle are in the same range as the tensile stresses and
      must be considered when analyzing the possible modes of failure. However, the
      mode of failure in shear is complex, and shear strength of the stem-cement
      interface is unknown at present.

PMID- 7820737
TI  - Osteonecrosis of the femoral head: current concepts and controversies.
AB  - Despite many investigations into ON of the femoral head, many issues remain
      unresolved. The pathogenesis in most cases is only speculative and may involve
      intravascular factors such as microemboli or extravascular factors such as
      increased interosseous pressure. MRI has emerged as the diagnostic test of choice
      for suspected early lesions, and radiographs should be used to diagnose and
      follow advanced lesions. Bone scanning can be useful for early diagnosis and CT
      scanning or tomography may help plan surgical procedures. The role of the
      functional exploration of bone is controversial. The natural history of early
      lesions is unknown; this makes it difficult to evaluate results of treatment.
      Radiographic ON will usually progress to collapse and arthrosis if treated
      nonoperatively. The role of core decompression or other joint preserving
      operations to prevent collapse is controversial, since the reports of success and
      complication rates have been extremely variable. These procedures are ineffective
      if used after radiographic collapse. Total hip replacement is the only
      satisfactory treatment for advanced symptomatic stages, but is relatively
      contraindicated in young active patients. Further research is needed to assess
      the natural history of early ON and evaluate the role of surgery in preventing
      progression.

PMID- 7820738
TI  - Late rupture of the posterior cruciate ligament after total knee replacement.
AB  - To our knowledge there have been no reports of late rupture of the posterior
      cruciate ligament (PCL) as a cause of instability in PCL-retaining total knee
      prostheses. In our experience of 150 total knee replacements using PCL-retaining
      prosthesis, three cases (2.0%) of late rupture of the posterior cruciate ligament
      have occurred, each leading to chronic instability, disabling pain, and revision
      arthroplasty. In each case rupture of the posterior cruciate ligament was
      confirmed at the time of revision arthroplasty. The use of a more constrained
      prosthesis led to a successful outcome in each case.

PMID- 7820739
TI  - The enigmatic diagnosis of posterior tibialis tendon rupture.
AB  - Posterior tibialis tendon rupture is a diagnosis that is often missed. This is
      thought to be secondary to nonspecific clinical findings and the lack of any
      laboratory or radiographic test to reliably confirm the diagnosis. We report
      sixteen cases of surgically confirmed posterior tibialis tendon rupture. Based on
      our review of these patients, the diagnosis of posterior tibialis tendon rupture
      should be strongly suspected in the adult patient presenting with a history of a
      twisting ankle injury and generalized medial ankle pain and swelling. A flexible,
      asymmetric pes planus and forefoot pronation deformity with absence of posterior
      tibialis tendon function on manual testing is seen on examination. This is
      associated with loss of ipsilateral heel inversion on bilateral heel rise. The
      patient is usually unable to perform ipsilateral single leg heel rise and has
      less severe pes planus of the contralateral foot. This study reviews the
      presentation, pathophysiology, diagnosis, and treatment of posterior tibialis
      tendon rupture.

PMID- 7820740
TI  - Fracture of the hook of the hamate: radiographic visualization.
AB  - The diagnosis of fracture of the hook of the hamate is rarely made at the time of
      the initial injury. Routine roentgenograms of the hand in the standard three
      positions do not visualize this structure. The carpal tunnel view (CTV) with
      hyperextension of the wrist may be too painful to position. A computerized
      tomography of the wrist in the transverse or axial plane will clearly and
      painlessly identify the fracture. Placing both hands and wrists in the praying
      position gives excellent comparison and documents any developmental bone
      abnormality. Scintigraphy, when positive, must be followed by tomography or a
      carpal tunnel view.

PMID- 7820741
TI  - Management of major arterial injuries of the limbs in 166 cases.
AB  - The charts of 166 patients with major arterial injuries (175 arterial repairs)
      inflicted during periods of peace and war time were reviewed. One hundred and
      sixty-seven (95%) of the arteries repaired remained patent. Nine patients had
      limbs which developed ischemic contracture. Nine patients required amputations.
      Follow-up data was obtained from seventy-five patients with an average follow-up
      of five years and one month (six months to thirty years). Early diagnosis, prompt
      treatment including fasciotomies when indicated, complete debridement,
      appropriate coverage, meticulous surgical technique, and simultaneous treatment
      of concomitant injuries are all crucial factors in successful limb salvage. Major
      arterial injuries of the limb occur frequently in our patient population,
      especially in time of war. Successful treatment of major arterial injuries may be
      life-saving, as well as allowing limb salvage and restoration of limb function.
      The purpose of this study is to review our experience with repair of major
      arterial injuries.

PMID- 7820743
TI  - Tomas Torquemada and some orthopaedic CPT coding problems (God is a comedian,
      playing to an audience who is afraid to laugh!).

PMID- 7820742
TI  - Treatment of difficult fractures and nonunions of the humerus and elbow with a
      modified Kuntscher nail.
AB  - A series of fourteen difficult fractures and nonunions of the humerus and elbow
      have been treated over a period of twenty-eight years with a modified Kuntscher
      Nail. A total of twenty-six operative attempts had been previously made in this
      group of fourteen patients. One patient had eight failed surgeries prior to
      treatment. Slots were placed along the spine of the nail for transfixion with
      screws. In two instances additional modification of the Kuntscher nail was made
      by attaching a plate to the end of the nail for fixation to the ulna after
      retrograde insertion into the humerus. One such device was used to fuse the
      elbow. The other was used to stabilize a low nonunion in which the elbow was
      already fused. Union was obtained in nine cases with failure in five. Four of the
      failures united with one additional surgery. The one failed case had a surgical
      neck fracture which was eventually treated with a Neer prosthesis. The method
      described may not be superior to other methods; however, it can be successful in
      obtaining union in difficult elbow and humerus fractures or nonunions resulting
      from multiple failed prior procedures.

PMID- 7820744
TI  - Ulnar subluxation of the extensor digitorum communis tendon: a case report and
      review of the literature.
AB  - Ulnar subluxation of the extensor digitorum communis tendon at the MCP joint
      occurs infrequently in the nonrheumatoid patient and is secondary to one of four
      reported etiologies: traumatic, spontaneous, congenital, or epileptic. If
      symptomatic, patients may present with pain, swelling, a sensation of the tendon
      "snapping", "catching", "locking", or the inability to fully extend the MCP
      joint. Conservative and operative interventions have been recommended as
      treatment options. In the acute traumatic dislocation (less than ten days post
      injury), satisfactory results may be obtained with simple splinting with the MCP
      joint in extension. Patients who have failed conservative management or have a
      more chronic or degenerative dislocation may require surgical correction. The
      successful surgical repair must meet two requirements: (1) the tendon must be
      accurately aligned over the MCP joint to diminish the forces causing the
      dislocation to occur, and (2) the repair must be able to withstand the ulnar
      forces incurred during flexion of the joint. Realignment of the extensor tendon
      and direct repair of the radial sagittal band may be sufficient in acute
      traumatic, congenital, or spontaneous cases if the tissue is sufficient. In
      chronic dislocations or in cases with atrophic or degenerative tissue,
      reconstruction with augmentation of the radial restraints to the extensor hood is
      advised.

PMID- 7820745
TI  - Bone metastasis from retinoblastoma.

PMID- 7820746
TI  - Simultaneous ipsilateral fracture of the supracondylar humerus and forearm in a
      child: a case report.

PMID- 7820747
TI  - Biomechanical research at Iowa.

PMID- 7820748
TI  - Anterior elbow dislocation associated with olecranon fractures--review of the
      literature and case report.

PMID- 7820749
TI  - Intraarticular dislocation of the patella.

PMID- 7820750
TI  - Why have we left Charnley low friction arthroplasty?

PMID- 7820753
TI  - The fate of autogenous tendon grafts.

PMID- 7820752
TI  - The collagen in normal ligaments.

PMID- 7820751
TI  - Drug treatment of soft tissue injuries efficacy and tissue effects.

PMID- 7820755
TI  - Magnetic resonance imaging of the epiphysis: an experimental study.
AB  - The purpose of this study was to determine if metabolically altered cartilage
      could be distinguished from normal cartilage in the epiphysis by magnetic
      resonance imaging. Epiphysis from ten New Zealand White rabbits and five newborn
      lambs were imaged before and after heat-killing. The physiological change
      produced was documented with tritiated thymidine and radioactive sulfate
      autoradiography. Magnetic resonance imaging could detect differences in the
      tissues produced by heat-killing. The changes were most pronounced in the marrow,
      less pronounced in the epiphyseal cartilage and least pronounced but still
      detectable in the growth plate.

PMID- 7820754
TI  - MRI in the diagnosis of knee injuries.

PMID- 7820756
TI  - Vertebral compression fractures: differentiation between benign and malignant
      causes.

PMID- 7820757
TI  - Recurrent shoulder dislocation.

PMID- 7820758
TI  - Epiphora associated with dacryops in a dog.
AB  - A six-month-old basset hound was presented with unilateral right epiphora and
      medial canthal and maxillary bone swelling. Skull radiographs and
      dacryocystorhinography revealed a nasal cyst, right nasolacrimal duct dilatation,
      and obstruction. Laboratory examination of the cyst confirmed the diagnosis of
      dacryops, a cyst of lacrimal gland origin. The cyst was treated successfully with
      surgical drainage and curettage.

PMID- 7820760
TI  - Mucinous oligodendroglioma of the spinal cord in a dog.
AB  - Intraspinal neoplasia in the dog is relatively rare and may be classified
      according to the location of the tumor. Extradural tumors are situated outside
      the dura mater. Intradural tumors may be subdivided into two classes, depending
      upon whether the tumor is located outside the spinal cord in the subdural space
      (intradural extramedullary) or within the spinal cord substance (intramedullary).
      Intramedullary tumors are the least commonly reported spinal cord tumors; most
      primary intramedullary tumors are astrocytomas, ependymomas, or
      oligodendrogliomas. Reported here are the clinical, radiographic, and
      pathological findings associated with a spinal cord oligodendroglioma in a dog.

PMID- 7820759
TI  - Canine necrotizing sialometaplasia: a case report and review of the literature.
AB  - Necrotizing sialometaplasia (NS) is a distinct, though rare disease of the
      salivary glands. Histologic findings in humans and dogs are identical, but the
      distribution of affected glands and clinical course are very different. Small
      terrier breeds are predisposed. Clinically, canine NS is characterized by nausea
      (i.e., ptyalism, lip smacking, gulping), dysphagia, and pain in the mandibular
      region. Surgical removal of the affected glands produces minimal, if any,
      improvement; however, transient administration of anticonvulsants has resulted in
      dramatic clinical improvement in three cases.

PMID- 7820761
TI  - Concurrent renal adenocarcinoma and polycythemia in a dog.
AB  - Concurrent renal adenocarcinoma and polycythemia were diagnosed in a 19-month
      old, female Rhodesian ridgeback. An unusually early presentation for this
      neoplasm, it is the second reported case of renal adenocarcinoma in a dog less
      than two years of age. Concurrent renal adenocarcinoma and polycythemia have been
      reported previously in four older dogs. In the dog of this report, clinical signs
      included brick-red mucous membranes, lethargy, a periodic systolic heart murmur,
      and engorged retinal vessels. A large retroperitoneal mass and pulmonary
      metastatic nodules were present at the time of diagnosis. Red blood cell count,
      packed cell volume, and hemoglobin concentration were greatly increased
      (12,940,000 red blood cells/microliter; 73.2%; and 26.6 g/dl, respectively).
      Histopathological diagnosis was renal adenocarcinoma. Polycythemia was the result
      of excessive erythropoietin production by the neoplasm.

PMID- 7820762
TI  - Ulcerative eosinophilic stomatitis in three Cavalier King Charles spaniels.
AB  - Ulcerative eosinophilic stomatitis affecting three Cavalier King Charles spaniels
      is described. The lesions are similar in gross appearance to previously reported
      palatine eosinophilic granulomas, but histologically they lack granuloma
      formation. The cause of the lesions is not known. Treatment with corticosteroids
      led to the resolution of one case and partial resolution of a second. A third
      case resolved spontaneously without therapy.

PMID- 7820763
TI  - Inhalant anesthetics and inspired oxygen: implications for anesthesia in birds.
AB  - A number of factors cause respiratory depression in anesthetized birds.
      Hypoventilation can be due to anesthetic-induced depression of the central
      nervous system, muscular relaxation of the muscles of respiration, and effects on
      central and peripheral chemoreceptors. Compared to mammals, respiratory function
      in birds may be more sensitive to the effects of inhalant anesthetics because of
      their effect on unique carbon dioxide (CO2)-sensitive intrapulmonary
      chemoreceptors located within the avian lung. High fractions of inspired oxygen
      also contribute to hypoventilation, possibly by depressing oxygen-sensitive
      chemoreceptors. This article is a review of the factors that cause respiratory
      depression in anesthetized birds.

PMID- 7820764
TI  - Multiple dental developmental abnormalities following canine distemper infection.
AB  - Multiple dental developmental abnormalities (e.g., dental impaction, partial
      eruption, oligodontia, enamel hypoplasia, and dentin hypoplasia) in a 10-month
      old, female, Tanzanian tropical mixed-breed puppy are reported. Various permanent
      teeth were involved. These included impacted mandibular canine and first and
      third premolar teeth; a partially erupted maxillary canine tooth; oligodontia of
      a mandibular fourth premolar tooth; enamel hypoplasia of the maxillary and
      mandibular canine teeth, incisors, and premolars; and dentin hypoplasia of the
      maxillary incisors, maxillary premolars, and mandibular premolars. The puppy had
      clinical canine distemper at the age of two months and had no history of any
      other systemic nor generalized infection prior to the time when the dental
      abnormalities were observed.

PMID- 7820765
TI  - Adverse side effects of oral antibacterial therapy in dogs and cats: an
      epidemiologic study of pet owners' observations.
AB  - This epidemiologic study surveyed pet owners for observations of adverse
      reactions to oral antibacterials which were prescribed to outpatients at a
      university teaching hospital. Multiple questions were asked of all clients whose
      dog or cat was treated during the 18-month study. The questionnaire was designed
      prospectively to define those reactions that clearly seemed to be medication
      related. In this study, owners noted a significant number of adverse side effects
      with erythromycin stearate administration to dogs. Trimethoprim-sulfadiazine was
      used most often in dogs but did not result in a substantial number of adverse
      reactions.

PMID- 7820766
TI  - Evaluation of the ICAGEN-Target canine ovulation timing diagnostic test in
      detecting canine plasma progesterone concentrations.
AB  - Accuracy of the ICAGEN-Targeta progesterone enzyme-linked immunosorbent assay
      (ELISA) test kit to measure plasma progesterone was compared to that of
      radioimmunoassay (RIA) in 166 canine samples. Overall agreement of ICAGEN-Target
      ELISA and RIA was 85% (141/166). Agreement of ELISA and RIA at high (5 ng/ml or
      greater), medium (greater than 1 ng/ml, less than 5 ng/ml), and low (0 to 1
      ng/ml) plasma progesterone concentrations was 96% (72/75), 73% (19/26), and 77%
      (50/65), respectively. Use of whole blood resulted in unreliable progesterone
      concentration results by ELISA when compared to plasma progesterone
      concentrations measured by RIA (n = 140). Use of this ELISA test kit to determine
      canine ovulation date should start within three to four days after onset of
      proestrus and continue every other day until the first detection of medium
      concentrations (greater than 1 ng/ml, less than 5 ng/ml). Daily plasma testing
      during the time of transition from medium to high (5 ng/ml or greater)
      concentrations was essential for determining ovulation date. The second or third
      day after the first appearance of high plasma progesterone concentrations using
      this kit should be the day of breeding for optimal reproductive performance.

PMID- 7820767
TI  - Primary rib tumors in 54 dogs.
AB  - Fifty-four dogs with primary tumors of the rib were evaluated. Thirty-four dogs
      had osteosarcomas, 15 dogs had chondrosarcomas, three dogs had hemangiosarcomas,
      and two dogs had fibrosarcomas. Forty-nine dogs had en bloc excision. Within the
      osteosarcoma group, nine animals received postoperative adjuvant chemotherapy.
      These animals had significantly longer median disease-free intervals (225 days)
      and median survival times (240 days) than dogs with osteosarcoma treated by
      surgery alone (median disease-free interval, 60 days; median survival, 90 days).
      Chondrosarcoma had a better prognosis (median disease-free interval, 1,080 days;
      median survival, 1,080 days) than osteosarcoma, hemangiosarcoma, or fibrosarcoma
      of the rib. Age, weight, sex, number of ribs resected, tumor volume, and total
      cisplatin dose did not influence survival nor disease-free interval.

PMID- 7820768
TI  - Concurrent lymphangioma, immune-mediated thrombocytopenia, and von Willebrand's
      disease in a dog.
AB  - Lymphangioma, immune-mediated thrombocytopenia (IMT), and von Willebrand's
      disease (vWD) were diagnosed by histology, hematology, and a coagulation profile
      in a 14-month-old, female dachshund. Clinical and laboratory findings included
      ecchymotic inguinolabial swelling, thrombocytopenia, positive platelet factor-3
      assay, prolonged buccal mucosal bleeding time, and subnormal von Willebrand
      factor antigen concentration and factor VIII activity. The IMT resolved with
      immunosuppressive glucocorticoid therapy. Histologic examination identified
      lymphangioma which was too extensive for surgical excision. The history and the
      clinical and laboratory findings were consistent with congenital vWD, although
      acquired vWD secondary to lymphangioma could not be ruled out.

PMID- 7820769
TI  - The intracapsular extraction of displaced lenses in dogs: a retrospective study
      of 57 cases (1984-1990).
AB  - Records of 48 dogs (57 eyes) that underwent intracapsular lens extraction (ICLE)
      of displaced lenses were reviewed. Preoperatively, 73% (19/26 eyes) of eyes with
      anterior luxations had secondary glaucoma compared to 43% (10/23 eyes) with
      subluxations and 38% (3/8 eyes) with posterior luxations. Forty-one of 57 eyes
      (72%) had vision and intraocular pressure (IOP) less than 30 mm Hg four to six
      weeks after surgery. This percentage declined to 61% (22/36 eyes) in three months
      and 53% (8/15 eyes) in 12 months. Eyes with glaucoma before ICLE had a lower
      success rate (66%) than eyes without (82%). Since secondary glaucoma was the most
      common cause of failure, this study suggests that removal of a subluxated lens or
      a posteriorly luxated lens should be recommended before the lens moves into the
      anterior chamber.

PMID- 7820770
TI  - Multiple metaphyseal involvement of a thymic lymphoma associated with
      hypercalcemia in a puppy.
AB  - A six-month-old, female German shepherd dog was presented because of depression,
      anorexia, vomiting, polyuria, and polydipsia of approximately 10 days' duration.
      The puppy was depressed, and pain could be elicited on palpation of both
      shoulders and hips. The most significant results of serum chemistries and
      hematology were hypercalcemia; increased blood urea nitrogen, creatinine, and
      alkaline phosphatase; and leukocytosis with neutrophilia. Thoracic radiographs
      revealed a large thymic mass, diagnosed on histological examination as a thymic
      lymphoma. Radiographs of the shoulders revealed destructive bone lesions
      involving the proximal metaphyses of the humeri, causing slipped epiphyses. Bone
      lesions were found at necropsy on the proximal and distal aspects of both humeri
      and femurs. Bone resorption was due to local neoplastic infiltration and presumed
      humoral factors secreted locally and systemically by neoplastic thymic
      lymphocytes.

PMID- 7820771
TI  - Primary osteosarcoma distal to the antebrachiocarpal and tarsocrural joints in
      nine dogs (1980-1992).
AB  - The medical records of nine dogs with primary osteosarcoma distal to the
      antebrachiocarpal or tarsocrural joint were reviewed. Eight of the nine dogs were
      treated with surgical removal of the primary tumor; seven received adjuvant
      chemotherapy; and one dog was treated with chemotherapy alone. Median survival of
      dogs in this series was 466 days. Six of the nine dogs died of causes
      attributable to osteosarcoma, and both skeletal and pulmonary metastases
      occurred. Survival of dogs with osteosarcoma distal to the antebrachiocarpal or
      tarsocrural joint was somewhat longer than survival of dogs with osteosarcoma of
      more common appendicular sites. However, these are aggressive tumors with a high
      potential for metastasis.

PMID- 7820772
TI  - Evaluation of pulse oximeter probes and probe placement in healthy dogs.
AB  - Placement of two different pulse oximeter probes, a finger (f) probe and a
      multisite (s) probe, was evaluated in six healthy, anesthetized beagles.
      Concurrent arterial blood gas values were compared to determine the most
      consistent (repeatable) and accurate (compared to calculated hemoglobin
      saturations) pulse oximeter probe and probe placement sites for subsequent use in
      awake dogs. Hemoglobin oxygen saturation was determined from arterial blood gas
      analysis (SaO2) and by pulse oximetry (SpO2) at full hemoglobin saturation (mean,
      99.5% SaO2) and at moderate desaturation (mean, 92.9% SaO2). Each probe was
      evaluated with three independent readings at seven different body sites
      (Achilles, ear, flank, lip, tail, toe, and tongue). Values for SpO2 obtained with
      the s probe demonstrated a significant correlation with SaO2 values (p = 0.014, R
      = 0.712) compared to the SpO2 values obtained with the f probe (p = 0.108). The
      best probe placement sites for the clip-on probes in this study were on the lip
      and tongue using the s probe; however, the ear, tail, and toe may be acceptable
      sites in awake dogs using a probe which maintains good contact across these
      vascular beds.

PMID- 7820774
TI  - The peak bone mass of Hawaiian, Filipino, Japanese, and white women living in
      Hawaii.
AB  - Our study compares the bone mass of Hawaiian, Filipino, Japanese, and white women
      living in Oahu, Hawaii. Eligible women ranged in age from 25 to 34; all had bone
      mass measurements at the spine, calcaneus, and proximal and distal radius. Their
      average bone mineral density (BMD) remained stable with age at all four bone
      sites, indicating that the age range 25-34 may represent the peak bone mass. Bone
      mass varied, however, between ethnicities; differences in BMD up to 11% were
      observed. The Hawaiian women had the greatest BMD, and whites had the second
      greatest BMD at the spine and calcaneus. The Japanese most frequently had the
      lowest BMD. Differences in body size partly explained the differences; most
      ethnic differences were reduced or eliminated after adjusting for height and
      weight. At the spine, the ethnic differences for BMD were also apparent with BMC
      and with vertebral area. Hawaiian and white women had greater values than
      Japanese or Filipino women. Differences at the proximal radius resembled the
      spine, except that whites had the widest proximal widths. The results were more
      complex for the distal radius. At the distal radius whites had the lowest BMD of
      the four ethic groups. The difference between whites and Hawaiians derived from
      the greater bone mineral content (BMC) of the Hawaiian women. By contrast, the
      difference between whites and the Japanese and Filipinos derived from the wider
      distal widths of the white women. Compared with the Japanese and Filipino women,
      the white women appeared to disperse their BMC at the distal radius across a
      wider bone width.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7820773
TI  - When should bone density measurements be repeated?
AB  - We calculated how long to wait before repeating bone mineral density (BMD)
      measurements to reassess fracture risk. Correlation results from serial
      measurements of 495 postmenopausal Japanese-American women were used to estimate
      95% confidence intervals (CI) for future BMD. After 7 years of follow-up, BMD
      correlations with the initial measurement ranged between 0.81 and 0.94, depending
      on age group and measurement site. In this analysis, the period between
      measurements was defined as the time required for the lower 95% CI to fall below
      the BMD value corresponding to doubling of fracture risk. Progressive bone loss
      causes fracture risk to double after 10 years, on average. However, the 95% CIs
      indicate that a second BMD measurement will detect risk doubling after only 2 or
      3 years for some women. For untreated, early postmenopausal women, the period
      between measurements was approximately 2-5 years for the radius and 4-6 years for
      the calcaneus, depending on the initial BMD level. The period was approximately 1
      year longer for women age 60 and older. Treatments that halve the bone loss rate
      would increase the period by 1-3 years. In the absence of a second measurement of
      BMD, the CI will continue to expand with time, corresponding to a wider range in
      risk between individuals, and a greater proportion of women will be at increased
      fracture risk. Obtaining a second BMD measurement pinpoints the patient's status
      within the precision of the measurement. We conclude that repeated BMD
      measurements will provide a more accurate estimate of fracture risk than a
      single, baseline measurement.

PMID- 7820775
TI  - Relations between calcidiol serum levels and bone mineral density in
      postmenopausal women with low bone density.
AB  - The relationship between vitamin D and bone density was studied in 150 selected,
      mature (45-74), postmenopausal women with a lumbar spine Z score below 0. Vitamin
      D status was evaluated using calcidiol serum levels. Serum calcitriol and
      parathyroid hormone (PTH) values were also evaluated in some subjects. Bone mass
      was evaluated by ascertaining bone density and Z and T scores in the lumbar spine
      and femur region. The reference group consisted of 25 premenopausal women. The
      postmenopausal group was divided into subgroups according to age, i.e., under or
      over 60 years old. Additionally, the whole group was also subdivided according to
      their lumbar spine Z scores into group I (Z > -1), group II (Z < -1; > -2), and
      group III (Z < -2). Group III of postmenopausal women had higher PTH and lower
      calcitriol levels than premenopausal women. Calcidiol serum levels were lower in
      postmenopausal women groups II or III than in the group I and premenopausal
      women. Calcidiol serum levels and the bone mass values for the lumbar spine were
      correlated positively in all the postmenopausal women; in the women over 60 years
      of age, calcidiol levels also correlated with the bone mass values expressed as
      the bone density in three femur regions: femoral neck, trocanter, and Ward's
      triangle. In conclusion, mature post-menopausal woman showed high PTH levels and
      low calcidiol and calcitriol values. Calcidiol status is significantly related to
      bone mineral density in the lumbar spine and in women over 60 years, calcidiol
      levels also correlated with bone density in the femur regions.

PMID- 7820776
TI  - Persistent bone-sparing effect of interleukin-1 receptor antagonist: a hypothesis
      on the role of IL-1 in ovariectomy-induced bone loss.
AB  - The recent finding that treatment with the interleukin-1 (IL-1) inhibitor,
      interleukin-1 receptor antagonist (IL-1ra) decreases bone loss and bone
      resorption in ovariectomized rats, strongly suggested that IL-1 mediates, at
      least in part, the effects of estrogen deficiency on bone resorption. Although in
      vitro studies have shown that IL-1 activates mature osteoclasts and stimulates
      osteoclastogenesis, the two main mechanisms by which estrogen deficiency
      stimulates bone resorption, it is still unclear whether IL-1 mediates both
      effects of estrogen deficiency in vivo. To investigate this matter, we have
      examined the changes in bone mineral density (BMD) which occur in ovariectomized
      rats after completion of 1 month of estrogen or IL-1ra treatment begun at the
      time of ovariectomy. Ovariectomy caused a marked decreased in BMD which was
      blocked by 17 beta estradiol and decreased by IL-1ra. Cessation of estrogen
      therapy was followed by a rapid induction of bone loss, indicating that estrogen
      blocks the activation and utilization of mature osteoclasts without depleting the
      bone microenvironment of osteoclast precursors and mature, inactive osteoclasts.
      In contrast, ovariectomized rats treated with IL-1ra maintained a stable bone
      density for the first 4 weeks after completion of the treatment. In these rats,
      bone loss resumed not earlier than 6 weeks after discontinuation of the IL-1ra
      treatment. Estrogen deficiency was necessary to unveil the bone-sparing effect of
      IL-1ra because in a control experiment in which rats were treated with IL-1ra for
      the 4 weeks before ovariectomy, BMD began to decrease immediately after
      ovariectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7820777
TI  - Hydrochlorothiazide inhibits osteoclastic bone resorption in vitro.
AB  - Long-term thiazide diuretic use is associated with higher bone mineral density
      and reduced hip fracture rates, which are attributed to increased serum calcium
      levels and decreased parathyroid activity that lead to decreased bone resorption.
      The present study shows that 1-100 microM hydrochlorothiazide (HCTZ) dose
      dependently inhibits bone resorption by isolated rat osteoclasts in the bone
      slice assay with an IC50 of approximately 20 microM. At these concentrations,
      HCTZ did not affect osteoclast survival on bone slices and had no effect on the
      proliferation of UMR-106 rat osteoblasts, indicating that the compound is not
      cytotoxic. However, such concentrations of HCTZ are unlikely to be achieved in
      man where therapeutic doses are usually 12.5-100 mg/day. That the in vitro effect
      of HCTZ on bone resorption may be due to inhibition of osteoclast carbonic
      anhydrase is discussed.

PMID- 7820778
TI  - Islet amyloid polypeptide (amylin) increases the renal excretion of calcium in
      the conscious dog.
AB  - Islet amyloid polypeptide (IAPP) is a member of the calcitonin/CGRP family and
      has been isolated from the beta-cell of pancreatic islets. Recent evidence
      suggests that this peptide may be involved in calcium metabolism in that its
      administration resulted in lowering of serum calcium levels. To determine the
      mechanism of IAPP-induced hypocalcemia, the peptide was infused at 50 pmol/min/kg
      for 90 minutes in conscious male mongrel dogs. Infusion of the peptide resulted
      in a modest decline in the total serum calcium concentration (10.4 +/- 0.2 to 9.4
      +/- 0.2 mg/dl; P < 0.05) and a concomitant increase in urinary calcium excretion
      (3.6 +/- 0.6 to 6.9 +/- 2.0 mg/dl; P < 0.01). Based on an extracellular volume of
      7 liter in a 28 kg dog, the total decrement in calcium due to IAPP was 41.3 +/-
      2.4 mg, whereas the total increase in urinary calcium was 3.2 +/- 0.7 mg. There
      were no detectable changes in calcitonin. We conclude that IAPP lowers serum
      calcium and increases the renal excretion of calcium independently of calcitonin.
      However, the calciuria can only account for a small component of the hypocalcemic
      effect and therefore, an additional calcium lowering effect of IAPP exits.

PMID- 7820779
TI  - Surgically induced uremia in rats. II: Osseous PTH-susceptible signaling systems
      as predictors of bone resorption.
AB  - Predicting the course of parathormone (PTH)-elicited bone turnover in both humans
      and experimental rat models with moderate chronic uremia, using only standard
      clinical chemistry analyses, is often difficult. Consequently, rat bone from 1 +
      2/3 nephrectomized animals, after 230 days of progressive renal failure, was
      examined for PTH-stimulated adenylate cyclase (AC) and phospholipase C (PL-C)
      activities. Correlations to biological parameters related to the function of bone
      and kidney were made. Reduced renal function was demonstrated by increased serum
      creatinine; circulating 1,25 dihydroxyvitamin D3 below detection level;
      diminished renal PTH-elicited AC activity; and decreased urinary cAMP excretion.
      PTH-activated renal PL-C was also reduced. However, no significant differences
      were seen in urine creatinine, calcium, phosphate, and hydroxyproline, nor in
      serum PTH, alkaline phosphatase, calcium, and phosphate. Notwithstanding, renal
      osteodystrophy developed as estimated by increased plasticity of the long bones,
      as well as reduction of the diaphyseal (Dd) and inner femoral mid-shaft (Di)
      diameters. Femoral cancellous bone exhibited a substantial elevation of both
      eroded surface (ES) and osteoid surface (OS) as well as a marked reduction in
      trabecular bone volume (TBV). Calvarial PTH-activated AC was enhanced, whereas
      corresponding PL-C was markedly reduced. PTH-enhanced AC correlated positively
      with ES and negatively with Di, respectively. PTH-enhanced PL-C, however,
      correlated positively with bone calcium content and negatively with ES. Our
      results indicate that bone modeling and remodeling are to a large extent related
      to PTH-elicited signaling systems, and cannot easily be predicted by standard
      clinical chemistry analyses.

PMID- 7820780
TI  - Recovery from pamidronate (APD): a two-year study in the dog.
AB  - The goal of this study was to find out if bone can recover after long-term
      administration of bisphosphonate. Disodium pamidronate (APD) was given orally by
      gavage to mature beagle dogs at doses of 0, 2.5, 12.5, and 25 mg/kg/day for 1
      year (0.1% concentration) and the animals were allowed to recover for another
      year. At sacrifice, the os ilium was used to determine bone mineralization
      profile and, subsequently, each density fraction was analyzed chemically. The
      ribs were used to determine the lattice parameters and the size of the apatite
      crystals of bone. The sternum was used to determine selected morphometric
      parameters using image analysis of specimen X-ray films and, subsequently, to
      determine bone mechanical properties using a 3-point bending technique. We found
      that the 12.5 and 25 mg/kg/day doses exhibit a significant shift towards greater
      mineralization versus control, whereas the lower dose (2.5 mg/kg/day) was
      indistinguishable from the controls. The lattice parameters and crystal size of
      bone apatite remained unchanged. The image analysis shows a dose-related increase
      in trabecular volume and thickness. The connectivity increased with dose but the
      anisotropy of bone remained unchanged. Both the elastic modulus and the maximum
      stress of bone remain unaffected by APD. We conclude that when dogs are treated
      with APD for 1 year, their bones can reestablish their physical-chemical
      characteristics (mineralization profile, chemistry, and crystal size/strain)
      after 1 year of recovery, provided that the treatment dose is 2.5 mg/kg/day. In
      addition, the mechanical properties of the bone remained unaffected and the gains
      in trabecular volume and thickness are maintained.

PMID- 7820781
TI  - Cyclosporin A does not affect the absolute rate of cortical bone resorption at
      the organ level in the growing rat.
AB  - The weanling rat, an animal model of rapid bone turnover, was used to evaluate
      the effects of various doses of cyclosporin A (CsA) on various bones during
      different time periods. Sprague-Dawley male rats were extensively prelabeled with
      3H-tetracycline during 1-3 weeks of age. At 4 weeks of age, four groups of rats
      were given daily subcutaneous injections: vehicle or CsA--low dose (10 mg/kg),
      intermediary dose (20 mg/kg), or high dose (30 mg/kg) for 7, 14, or 28 days.
      Three different whole bones--the femur (low turnover), scapula (moderate
      turnover), and lumbar-6 vertebra (high turnover) were harvested intact at 4, 5,
      6, and 8 weeks of age. The whole bones were assayed weekly for total dry defatted
      weight, calcium mass (formation), and loss of 3H-tetracycline (bone resorption)
      following treatment with CsA. Serum CsA levels, calcium creatinine, and alkaline
      phosphatase were measured weekly. Significant decreases in serum calcium and
      alkaline phosphatase were observed at 1 and 2 weeks, and were normalized by 4
      weeks of treatment. No significant changes in serum creatinine were noted. For
      all three doses of CsA, no effect was observed on the absolute rate of cortical
      bone resorption of three different, whole bones over three time periods. Body
      weight and bone formation in treated animals was significantly smaller in a dose-
      and time-related fashion compared with control animals at sacrifice. However,
      compared with the initial control animals, body weights and bone masses of the
      final treated animals were much larger, suggesting that the smaller bone masses
      were due to insufficient growth and slow gain in bone mass.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7820782
TI  - Alternative splicing of the mouse amelogenin primary RNA transcript.
AB  - A heterogeneous mixture of amelogenins can be extracted from developing tooth
      enamel matrix. In an attempt to discover the extent to which alternative splicing
      of the amelogenin primary RNA transcript can generate unique isoforms, we have
      conducted a thorough search for cDNAs amplified by reverse transcription
      polymerase chain reaction (RT-PCR). Over 2400 colonies were screened by colony
      hybridization. Seven different alternatively spliced amelogenin mRNAs were
      isolated. The predicted translation products of the messages are 194, 180, 156,
      141, 74, 59, and 44 amino acids in length. RT-PCR amplification products not
      predicted by these seven amelogenin cDNAs were characterized. The intron
      separating exons 5 and 6 was cloned and sequenced. Using rapid amplification of
      cDNA ends (RACE) techniques, the 5' ends of the amelogenin mRNAs were cloned and
      characterized. The finding that the same exon 1 is common to all of the cloned
      mRNAs indicates that mouse amelogenin is transcribed from a single promoter. The
      mouse amelogenin transcription and translation initiation sites, the 5'
      untranslated leader, and the segment encoding the signal peptide were determined.
      The distinctly nonamelogenin-like exon 4, first observed in human amelogenin
      cDNAs, has also been found in mice. Antibodies were raised to synthetic exon 4
      encoded polypeptides and used to immunostain Western transfers and histologic
      tooth sections.

PMID- 7820783
TI  - The effects of the insulin-like growth factors and transforming growth factor
      beta on the Jun proto-oncogene family in MC3T3-E1 cells.
AB  - Previous studies have demonstrated that when cells of the mouse osteoblastic cell
      line MC3T3-E1 are exposed to IGF-I and IGF-II they exhibit rapid and transient
      induction of the transcript from the proto-oncogene c-fos [8]. To clarify the
      relationship between induction of cell proliferation and proto-oncogene
      expression in MC3T3-E1 cells, the acute affects of IGF-I and IGF-II, growth
      factors that stimulate cell proliferation, and of TGF-beta 1, which inhibits cell
      proliferation, northern analyses with cDNA-derived probes for the proto-oncogenes
      c-jun, jun-B, and jun-D were undertaken. Concurrent northern analyses with a
      probe for c-fos extended our previous results to include the effect of TGF-beta 1
      on c-fos. IGF-I does not induce the c-jun, jun-B, or jun-D transcripts, the
      former and latter being produced at detectable levels constitutively. After 1
      hour of exposure to IGF-II the c-jun transcript response ranges from onefold to
      13-fold and the jun-D transcript response ranges around two-fold. After 1 hour of
      exposure to TGF-beta 1, the jun-B transcript response ranges from eightfold to 24
      fold, the c-fos transcript response ranges between sixfold and sevenfold. The
      differences observed in the magnitude and kinetics of the induction provoked by
      these growth factors is consistent with the presence of a regulatory circuit
      acting through the Jun family members which may act to stimulate transcription
      differentially when bound to DNA either as homodimers or, with Fos family
      proteins, as heterodimers.

PMID- 7820784
TI  - On animal models for studying bone adaptation.

PMID- 7820785
TI  - On animal models for studying bone adaptation.

PMID- 7820786
TI  - The Part II examination: effect on IMGs.

PMID- 7820787
TI  - Physician happy to be blown north.

PMID- 7820788
TI  - Physicians forced south, prevented from changing fields.

PMID- 7820789
TI  - Physicians forced south, prevented from changing fields.

PMID- 7820790
TI  - Physicians forced south, prevented from changing fields.

PMID- 7820791
TI  - Physicians forced south, prevented from changing fields.

PMID- 7820792
TI  - Interactions between lithium and NSAIDs.

PMID- 7820793
TI  - Guide to pregnancy risk grading a useful template.

PMID- 7820794
TI  - Screening strategies for colorectal cancer.

PMID- 7820795
TI  - Physicians concerned about the environment.

PMID- 7820796
TI  - Size of names in drug ads.

PMID- 7820797
TI  - Why do pregnant women smoke and can we help them quit?
AB  - As observed by Dr. Linda Dodds (see pages 185 to 190 of this issue), there has
      been little change in recent years in the smoking rate of about 30% among
      pregnant women in Nova Scotia. Women who smoke during pregnancy tend to be young,
      unmarried, undereducated and multiparous and tend not to go to prenatal classes.
      Many pregnant women find it extremely difficult to stop smoking even when they
      understand the risks to the fetus. Routine advice given by physicians on smoking
      cessation is clearly ineffective. However, informed physicians who recognize the
      difficulty of quitting and offer support and advice in a systematic way can help
      women to progress through the stages of the smoking cessation process.

PMID- 7820798
TI  - Basic statistics for clinicians: 2. Interpreting study results: confidence
      intervals.
AB  - In the second of four articles, the authors discuss the "estimation" approach to
      interpreting study results. Whereas, in hypothesis testing, study results lead
      the reader to reject or accept a null hypothesis, in estimation the reader can
      assess whether a result is strong or weak, definitive or not. A confidence
      interval, based on the observed result and the size of the sample, is calculated.
      It provides a range of probabilities within which the true probability would lie
      95% or 90% of the time, depending on the precision desired. It also provides a
      way of determining whether the sample is large enough to make the trial
      definitive. If the lower boundary of a confidence interval is above the threshold
      considered clinically significant, then the trial is positive and definitive, if
      the lower boundary is somewhat below the threshold, the trial is positive, but
      studies with larger samples are needed. Similarly, if the upper boundary of a
      confidence interval is below the threshold considered significant, the trial is
      negative and definitive. However, a negative result with a confidence interval
      that crosses the threshold means that trials with larger samples are needed to
      make a definitive determination of clinical importance.

PMID- 7820799
TI  - Availability of thrombolytic therapy in rural Newfoundland and Labrador.
AB  - OBJECTIVE: To determine the availability of thrombolytic therapy in rural
      Newfoundland and Labrador. DESIGN: Self-administered questionnaire mailed to
      staff at health care facilities. Respondents were sent two reminders by mail, and
      questionnaires not returned were completed through telephone interviews. SETTING:
      Rural health care facilities, including hospitals, 24-hour clinics and satellite
      clinics. PARTICIPANTS: All chief medical officers, nursing supervisors and
      administrators in the 34 government-funded rural health care facilities in
      Newfoundland and Labrador. OUTCOME MEASURES: Number of facilities offering
      thrombolytic therapy to patients with acute myocardial infarction (AMI) in 1992.
      For each facility: number of patients presenting with AMI during that year,
      number of these patients who received thrombolytic therapy, number of staff
      trained in advanced cardiac life support, travel time to the nearest referral
      centre, population served and number of beds. RESULTS: Of the 34 rural health
      care facilities in Newfoundland and Labrador, 91% (31/34) responded to the
      survey. Thrombolytic therapy was offered in 93% (13/14) of the rural hospitals,
      22% (2/9) of the 24-hour clinics and none of the single-physician satellite
      clinics. In 1992, 390 patients with AMI presented to these health care
      facilities; 39% of these patients presented to facilities that did not offer
      thrombolytic therapy. CONCLUSIONS: Thrombolytic therapy has been successfully
      introduced in many of the rural and isolated health care facilities in
      Newfoundland and Labrador. An important factor in this success is continuing
      medical and nursing education on the effectiveness of thrombolytic therapy and
      the skills needed to provide it. Cost-effectiveness data are needed to determine
      whether it is reasonable to offer this therapy in isolated, low-volume clinics.
      More research on the outcomes in patients receiving thrombolytic therapy in rural
      facilities is also needed.

PMID- 7820800
TI  - Prevalence of smoking among pregnant women in Nova Scotia from 1988 to 1992.
AB  - OBJECTIVE: To determine the prevalence of smoking during pregnancy in Nova Scotia
      and to identify women at high risk of smoking during pregnancy. DESIGN:
      Population-based descriptive study. SETTING: All hospitals providing obstetric
      services in Nova Scotia. PATIENTS: All 60 754 women residing in Nova Scotia who
      had a baby in hospital between 1988 and 1992; smoking data were available for
      57,750 (95.1%) of them. OUTCOME MEASURES: Proportion of women who smoked during
      pregnancy and the maternal smoking rates by age, marital status, parity,
      attendance at prenatal classes and residence. RESULTS: Overall, 32.4% of the
      women smoked at some point during their pregnancy. The rate was highest among the
      women less than 20 years of age (47.0%) and decreased with each increasing 5-year
      age interval. Overall, the unmarried women were 2.1 times as likely to smoke as
      the married women. The smoking rates were highest among the women who were para 3
      or greater regardless of age (women less than 20 were excluded here, since very
      few had such a parity). Of the nulliparous women, those who attended prenatal
      classes were less likely to smoke during pregnancy than those who did not attend.
      There was no relation between urban or rural residence and smoking rates. The
      smoking rates decreased little between 1988 and 1992 and in fact increased among
      the women 35 and over and among those who were para 3 or greater. CONCLUSIONS:
      The smoking rates among pregnant women in Nova Scotia changed little between 1988
      and 1992. Therefore, it seems that current strategies for smoking cessation have
      not been successful. Since prenatal classes are more likely to attract nonsmokers
      than smokers, other avenues for education and cessation are necessary.

PMID- 7820801
TI  - Critical clue to ethylene glycol poisoning.
AB  - The authors report the case of a man 49 years of age with near-fatal ethylene
      glycol poisoning. Detection of calcium oxalate monohydrate crystals in the urine
      was the only real-time confirmation of the diagnosis. The case illustrates that,
      if the toxin has already been metabolized, familiarity with the appearance and
      significance of this unusual form of calcium oxalate crystal may be the key to an
      accurate diagnosis.

PMID- 7820802
TI  - Islet cell mass and predisposition to non-insulin-dependent diabetes mellitus.
AB  - A research team at the University of Manitoba's Faculty of Medicine is searching
      for the genetic marker that determines pancreatic islet cell mass. If this
      research is successful it may be possible to identify people with a genetic
      predisposition to non-insulin-dependent diabetes mellitus. Little is known about
      islet cells, although it is believed that they achieve peak mass in the neonatal
      period or even in utero. Led by Dr. Liam Murphy, the research team is looking at
      chromosome 6 for the homeobox genes that control foregut and pancreatic
      development. They are at the stage of cross-breeding mice in order to follow a
      trend in their genetic make-up. Once the determinants of islet cell mass in mice
      are found the search for the corresponding genes in humans can begin. Their
      research is expected to take several years to complete.

PMID- 7820803
TI  - Evidence-based medicine.
AB  - Clinical practice guidelines are an important product of the National Committee
      to Advise on Tropical Medicine and Travel (CATMAT). Recent guidelines have been
      published on the guiding principles for clinical practice guidelines. The ninth
      principle states: "Clinical practice guidelines should: (a) cite the specific
      evidence bearing upon the conclusion, (b) indicate the strength of the evidence
      [and] (c) specify the date of the most recent evidence considered." The following
      is CATMAT's statement on evidence-based medicine and the scales used to grade its
      recommendations.

PMID- 7820804
TI  - Statement on travellers' diarrhea. Committee to Advise on Tropical Medicine and
      Travel.

PMID- 7820805
TI  - Low-osmolar-dye intravenous delivery systems.

PMID- 7820806
TI  - Generation X arrives at medical school to find changing expectations, growing
      pressures.
AB  - Students entering medical school today face a health care system that is vastly
      different from the one new students experienced in the 1970s and 1980s. Michael
      OReilly interviewed five first-year students from the University of Western
      Ontario to learn about the hopes and dreams of medicine's next generation and the
      pressures facing these students. The Class of '98 doesn't appear intimidated by
      the cutbacks practising physicians are facing. As one student put it, these
      students won't be yearning for the "good old days" because "we don't have any
      good old days to remember."

PMID- 7820807
TI  - Population-health concept challenges dominance of clinical medicine.
AB  - As the emerging policy concept of population health challenges the dominance of
      clinical medicine in health care, many question how it will affect "grass-roots"
      physicians. Although primarily a planning tool for policymakers that provides a
      framework to study the determinants of health, health outcomes and health
      interventions, population health can also be applied to medical practice. The CMA
      identified population health as a priority issue in March 1994, and has sponsored
      several presentations and workshops on the issue. On Jan. 23 three CMA Councils
      will meet jointly to discuss the implications this new policy holds for
      physicians.

PMID- 7820809
TI  - Another statistic in the war on smoking.
AB  - Bill Trent, a longtime contributor to CMAJ, died last March before he had time to
      write an article chronicling his battle with smoking-related chronic obstructive
      pulmonary disease. His widow Dawn Trent has done the job in his memory. The
      article, which marks Canada's National Non-Smoking Week, details the emotional
      and monetary costs that accompany smoking-related disease.

PMID- 7820808
TI  - They were all children once....
AB  - CMAJ asked Dr. Richard Hodder, the respirologist who treated Bill Trent (see
      following article), to offer his perspective on the war against smoking. In this
      article he recalls some of the patients he lost because of smoking and the steps
      that should be taken to combat tobacco use.

PMID- 7820810
TI  - Marginal capacity: the dilemmas faced in assessment and declaration.
AB  - Ontario is adopting informed-consent legislation that reflects increasing
      emphasis on patient autonomy and self-determination. Capacity assessment and
      declaration by physicians and other health care professionals are pivotal under
      the new legislation. While grossly capable or incapable patients provide few
      management difficulties, marginally capable patients provide a challenge for
      physicians who must assess capacity, and decisions concerning them emphasize the
      ethical dilemma involved in any declaration of incapacity. Our 1994 Logie Medical
      Ethics Essay first-prize winner, Vincent Ho, examines the issues that clinicians
      must consider when assessing marginally capable patients.

PMID- 7820811
TI  - Distribution of three microvillar enzymes along the small intestinal crypt-villus
      axis.
AB  - Aminopeptidase N (ApN), dipeptidyl peptidase IV (DPP IV) and sucrose-isomaltase
      (S-I) are differentially expressed along the pig jejunum crypt-villus axis.
      Quantitative immunoelectron microscopy and enzyme cytochemistry show that DPP IV
      and S-I are expressed in enterocytes along the entire length of the axis, whereas
      ApN is found mainly in the villar and upper crypt enterocytes. All three enzymes
      are detected in the basolateral membrane at all levels along the crypt-villus
      axis, although ApN and S-I only occurred at low intensities in the villus region.
      The microvillar/basolateral labelling ratio for the three enzymes increases to a
      varying degree for the three enzymes along the axis suggesting that the sorting
      efficiency to the apical membrane improves at least for ApN and S-I as the cells
      mature. These findings might indicate that the enterocytes change from a
      transcytotic to a direct apical transport as the enterocytes mature.

PMID- 7820812
TI  - Melanosis (haemosiderosis) ilei.
AB  - We report here a case of melanosis ilei where grossly visible greyish black
      pigmentation of the ileal mucosa was discovered at autopsy. Light microscopy
      showed Prussian blue positive pigment granules in macrophages in the lamina
      propria forming the core of villi. Ultrastructural examination showed that the
      pigment granules had the morphology of siderosomes which are known to be the
      electron microscopic equivalent of the haemosiderin granules seen with the light
      microscope. We know of no previous report where pigmentation of the ileal mucosa
      was ascribed to the presence of haemosiderin.

PMID- 7820813
TI  - Interleukin-2 alters the positions of capillary and venule pericytes in rat
      cremaster muscle.
AB  - Interleukin-2 (IL-2) mediates regression of metastatic cancer, but its
      therapeutic efficacy has been limited by toxicities which occur secondarily to IL
      2 induced macromolecular leakage from microvessels. Previous studies have
      indicated that pericytes function in an endothelial cell junction-dependent
      manner in lung capillaries and cremaster muscle venules, possibly to limit
      cellular and macromolecular leakage. The purpose of this investigation was to
      determine if pericyte positioning on skeletal muscle capillaries was junction
      related, and if it was altered by IL-2. Anesthetized rats received intravenous
      injections of fluoroscein isothiocyanate conjugated to albumin. The cremaster
      muscle model of microcirculation was used in conjunction with intravital
      fluorescence microscopy to monitor changes in interstitial fluorescence which was
      used as an index of macromolecular leakage. IL-2 induced a progressive increase
      in interstitial albumin which started within 30 min of application and continued
      to increase until the end of the experiment at two hours. Cremaster muscle tissue
      was fixed and prepared for examination by transmission electron microscopy. A
      digitizing platter and morphometric software were used to quantify pericytes near
      vs away from endothelial cell junctions of capillaries and venules. In
      microvessels from animals in the control group, pericytes were randomly
      positioned on capillaries, and concentrated at endothelial cell junctions of
      venules. After treatment with IL-2, capillary pericytes were concentrated at
      junctions. Venular pericyte density also increased in endothelial junctional
      regions. IL-2 appears to alter the distribution of pericytes in the
      microcirculation, perhaps by induction of contraction.

PMID- 7820814
TI  - Extensive networks of TMPase positive basal lysosomes are present in fetal rat
      gastric epithelium before overt differentiation.
AB  - The rat gastric epithelium of 17 to 19 days of intrauterine life changes from a
      pseudostratified epithelium to a simple columnar epithelium. From a flat
      epithelium at 17-18 days, groups of epithelial cells begin to invaginate towards
      a cellularly rich mesenchyma and foveolae appear at 19 fetal days.
      Ultrastructural differentiation of the first cells of gastric glands occurs at 19
      days. The ultrastructure of the undifferentiated cells at 17-18 fetal days shows
      extensive distribution of granules in the basal cytoplasm, near the basal lamina.
      To investigate the nature of these structures, enzyme cytochemistry was carried
      out. Acid phosphatase and trimetaphosphatase activities were demonstrated
      cytochemically in the gastric epithelium of the fetal rat. Whereas acid
      phosphatase positive lysosomes were observed mainly in typical round lysosomes,
      near the Golgi, a strong positive reaction for trimetaphosphatase, at 17 and 18
      fetal days, was present in granules and tubular structures located in the basal
      cytoplasm. This reaction was coincident with the observed basal granules. At 19
      days, the number of basal TMPase positive lysosomes was diminished, but other
      lateral tubular and vesicular positive structures were seen. The presence of
      coated pits in the basal membrane and microtubules and coated vesicles between
      tubular lysosomes, at 17-18 days, just before overt differentiation, reinforces
      the possibility of the association of this kind of lysosome with endosomes and
      the internalization of receptors.

PMID- 7820815
TI  - Changes in the neurosecretory axons of the neural lobe of the hypophysis of rats
      treated with met-enkephalin. An ultrastructural study.
AB  - Following administration of met-enkephalin into the third ventricle of rats of
      both sexes, an ultrastructural-morphometric study was carried out of the neural
      lobe of the hypophysis, comparing the results with those obtained in untreated
      animals, controls (injected intraventricularly with distilled water) and animals
      previously receiving naloxone intraperitoneally. In the untreated and control
      animals, both males and females, there was a high percentage (about 70%) of
      neurosecretory axons considered to have a normal morphology; after met-enkephalin
      administration, this percentage decreased and was accompanied by a rise (slightly
      more pronounced in the females) in the percentage of degranulated axons and a
      slight rise in axons with a morphology indicative of regenerative and
      degenerative phases. Previous administration of the opiate antagonist naloxone
      led to a rise in the number of axons in the degenerative phase with respect to
      the other groups of animals; this occurred in both sexes.

PMID- 7820816
TI  - On the ultrastructure of the spermatozoa in the Siberian hamster (Phodopus
      sungorus campbelli).
AB  - Spermatozoa of the Siberian hamster were examined using transmission and scanning
      electron microscopy. The sperm are approximately 119 microns in length and
      exhibit a falciform head typical of murine rodents. A rod-like structure runs
      almost the entire length of the subacrosomal space within the subacrosomal
      cytoskeleton. Scrolls of redundant nuclear membrane are consistently asymmetric
      on concave and convex sides of the sperm head with the convex side presenting
      much more elaborate whorls. Mitochondria in the middle piece number approximately
      133 pairs and present either one or two distinct cross-sectional profiles.
      Determining the number of mitochondrial pairs is presented as a means of
      distinguishing among the various species or subspecies of Phodopus. Viewed in
      longitudinal section, the annulus also presents two different configurations; one
      profile is cuneiform, the other semilunar. The axonemal complex is typical of
      most rodent sperm flagellae. Dense fibers 1, 5 and 6 are substantially larger and
      fiber 9 is somewhat larger in diameter than the rest.

PMID- 7820817
TI  - Actin expression in some Platyhelminthe species.
AB  - Actin expression in some Platyhelminthe species was demonstrated by western
      blotting and immunocytochemical analysis using two distinct anti-actin
      antibodies: the anti-total actin that reacts against all actin isoforms of higher
      vertebrates and the anti-alpha SM-1 that recognizes the alpha-smooth muscle
      (alpha SM) isotype of endothermic vertebrates (Skalli et al., 1986). Western
      blotting experiments showed that all species tested, including some free-living
      Platyhelminthes (Tricladida and Rhabdocoela) and the parasitic Fasciola hepatica,
      were stained by anti-total actin antibody while only Dugesidae and Dendrocoelidae
      showed a positive immunoreactivity against anti-alpha SM-1. These results were
      confirmed by cytochemical immunolocalization using both avidin biotin conjugated
      peroxidase reaction on paraffin sections, and immunogold staining on Lowicryl 4KM
      embedded specimens. Our findings may contribute to the understanding of
      Platyhelminthes phylogeny.

PMID- 7820818
TI  - Lipid-rich residual bodies in the human thyroid gland: ultrastructural,
      histochemical, and morphometric study.
AB  - Eleven samples of surgical and autopsy thyroid tissue were studied by classical
      histology, histochemistry, immunohistochemistry, light microscope quantitation
      and transmission electron microscopy in order to characterize lipid-rich residual
      bodies (LRRBs) previously reported in human myometrium. The following
      observations were made: 1) LRRBs were found largely in follicular epithelial
      cells; 2) they had exactly the same histochemical, immunohistochemical and
      ultrastructural characteristics as LRRBs from myometrium; 3) they had a
      distinctive distribution and morphology compared with lipofuscin; 4) a lysosomal
      nature was confirmed by their content of acid phosphatase and cathepsin D; 5)
      they were virtually absent from both the new-born thyroid and from thyroid
      carcinoma; 6) there was a statistical linear correlation between LRRB frequency
      and patient age. In conclusion, LRRBs have been demonstrated in an extra-uterine
      location, and are confirmed as residual lysosomes, probably having been involved
      in lipid metabolism.

PMID- 7820819
TI  - Atypical basal bodies in a cat with immotile-cilia syndrome.
AB  - Atypical basal bodies from the oviductal mucosa of a female, 2.5-years-old cat
      suffering from immotile-cilia syndrome are described. The microtubular pattern
      was observed in 250 cross-sectional basal bodies. Four basal bodies (1.6%) had a
      defective number of microtubular triplets resulting in the appearance of so
      called 'half-centriole' type. Two out of 100 longitudinal basal bodies showed
      duplicating striated rootlets and only one had an additional set of nine
      subdistal appendages, so that two basal feet arose from a single basal body.
      Electron-dense material and isolated microtubules into the lumen of some basal
      apparatuses were occasionally seen. It is known that centrioles and basal bodies
      show an unusual degree of constancy in size, shape and geometrical configuration,
      so that their abnormalities are very rare.

PMID- 7820820
TI  - Nuclear bodies associated with core particles of hepatitis B virus in a healthy
      carrier.
AB  - An unusual association of nuclear bodies (NB) with core particles of hepatitis B
      virus (HBV) is described in a healthy carrier who histologically showed ground
      glass hepatocytes with occasional sanded-nuclei. Ultrastructurally, many
      hepatocytes had typical features of HBV infection. Unexpectedly, a few cells
      contained previously undescribed complexes of NB studded with a number of HBV
      core particles. The ultrastructural characteristics of these complexes and their
      possible relation to HBV morphogenesis are briefly discussed.

PMID- 7820821
TI  - Repercussion of craniopharyngioma on the morphology of the rostral wall of the
      III ventricle. A combined TEM and SEM study.
AB  - Using a combined scanning and electron microscope technique, the repercussion on
      the rostral wall of the III ventricle in a patient affected with a
      retrochiasmatic craniopharyngioma with growth in the ventricular direction were
      analysed. The apical surface of the ependymocytes was found to be free of cilia,
      although there were numerous microvilli. The most striking finding appreciated
      with the scanning electron microscope was the presence of bulbous protrusions
      towards the lumen of the ventricle; these were formed of cells with shapes, sizes
      and surface characteristics different from the rest of the ependyma, which
      appeared flattened. The ultrastructural study revealed the presence of large
      numbers of filaments and junction complexes both in the ependymal and
      subependymal cells. Additionally, the protruded zones corresponded to areas
      showing different degrees of cellular disorganization.

PMID- 7820822
TI  - Gene therapy for cancer.
AB  - Advances in molecular biology and technology now being made will open the way to
      using gene transfer as a therapeutic option for patients with cancer. Since there
      are > 5,000 known genetic diseases, the potential impact of these techniques is
      enormous. Possibilities for the application of gene therapy are emerging and
      along with them complex safety, ethical, and financial issues that will require
      resolution. Many of these concerns will become relevant to the oncology nurse,
      who will need to understand the science, ethics, safety considerations, and
      impact of this experimental therapy on the patient. Since gene therapy is a
      rapidly evolving method of treatment, it will be a challenge to remain up to date
      and knowledgeable.

PMID- 7820823
TI  - Knowledge of malignant melanoma and how it relates to clinical practice among
      nurse practitioners and dermatology and oncology nurses.
AB  - Cutaneous malignant melanoma (CMM) is a growing health problem in the United
      States. This study evaluated nurses' frequency of skin cancer assessment, ability
      to recognize CMM, knowledge of risk factors and preventive measures, teaching
      practices, and barriers to skin cancer assessment. The sample (n = 178) consisted
      of nurse practitioners (NP), oncology nurses (ON), and dermatology nurses (DN).
      The participants indicated that skin cancer assessment was within their scope of
      practice but reported frequencies of performance were low. NP scored lower in
      overall knowledge, although they had received the highest level of formal skin
      cancer education (p < 0.05). Recognition of melanoma was moderate, with scores of
      54-68% for the three groups. Recognition scores for premalignant and benign
      lesions were lower. Frequency of skin cancer assessment and teaching were higher
      for DN (p < 0.05). Total knowledge scores were not predictive of teaching
      practices. Time limitations and inadequate knowledge were barriers that inversely
      correlated with frequency of skin cancer assessment. Findings suggest that
      individual CMM knowledge and experience correlated highly with frequency of
      assessment and teaching. Programs are needed to educate nurses in skin cancer
      prevention and detection. The broader implications for future research will be
      presented.

PMID- 7820824
TI  - Meaning of touch to hospitalized Puerto Ricans with cancer.
AB  - This ethnographic study was undertaken to elicit the meaning of nurse's touch for
      hospitalized Puerto Rican patients with cancer. The key informants were eight
      cancer patients at a tertiary 12-bed oncology research unit in Puerto Rico. Data
      gathering methods included participant observation and several ethnographic
      interviews during a month period. Content analysis was used to identify pattern
      of behavior and meaning. Analysis of the field notes and interviews was done to
      search for domains. Theme analysis was used in the search for the relationship
      among domains. In the analysis of the patient interviews, two types of touch were
      identified: procedural and affective touch. The predominant theme about
      perception of nurse's touch was that of conveying confidence. Confidence was
      related to the patient's increase in positive expectation as much as the
      possibility of recovery from the cancer illness. The confidence theme was
      represented by two domains: the enhancement of the abilities of the patient for
      coping and through the acceptance of the patient as a person during their illness
      experience.

PMID- 7820825
TI  - Traditional healers and perceptions of the causes and treatment of cancer.
AB  - The observation that some Nigerian patients use alternative health care services
      when they perceive that one medical system has failed them provided the impetus
      for this survey. The purpose of the survey was to understand why some Nigerian
      patients rely on traditional healers for cure of cancer by exploring the
      perceptions of Igbo traditional healers from Anambra State of Nigeria about the
      causes and treatment of cancer. Implications of the different meanings of illness
      and disease to patients and physicians provided the theoretical framework for
      understanding the cultural context of the study. Findings have ethical, moral,
      and cultural implications for professional nursing practice, education, and
      research.

PMID- 7820826
TI  - Attitudes and beliefs regarding spiritual care. A survey of cancer nurses.
AB  - Why nurses neglect spiritual care issues remains unclear. Therefore, a
      questionnaire designed to assess oncology nurse clinicians' attitudes and beliefs
      about spiritual care was mailed to a stratified, random sample of 700 Oncology
      Nursing Society members within the United States. Data from the 181 respondents
      were analyzed using descriptive and multivariate statistics (for quantitative
      items) and content analysis (for essay questions). Analysis of data revealed both
      a positive regard for spiritual care within nursing, and relationships between
      beliefs and attitudes about spiritual care and self-reported spiritually,
      religiosity, ethnicity, work role, and education. Recommendations are for
      inclusion of theoretical and practical aspects of spiritual care in nursing
      education and for further investigation of nurses' attitudes and beliefs
      regarding spiritual care.

PMID- 7820827
TI  - Importance of nausea.
AB  - Oncology nurses and patients identify nausea and vomiting as the two most
      distressing side effects of chemotherapy. The onset and duration of nausea and
      vomiting in patients receiving chemotherapy may vary. Inadequate control of
      emesis in the first 24 h following chemotherapy can lead to anticipatory nausea
      and vomiting and poor control in subsequent cycles of treatment. It may also
      result in delays or refusal by the patient to have further treatment. In
      addition, excessive nausea, as well as vomiting, can lead to a multitude of
      physical, psychologic, and social problems. It is therefore important that nausea
      is controlled equally as well as vomiting. Recent clinical research into new
      antiemetic therapy has highlighted the need for standard criteria for the
      assessment of nausea and vomiting. Assessment should include nausea as a separate
      phenomenon that may occur in the absence of vomiting and can be equally, if not
      more, distressing. Objective measures are suitable for the assessment of
      vomiting, but are not available for assessment of nausea because it is a
      subjective phenomenon. The purpose of this article is to present evidence
      supporting the idea that patient reporting using a four-point scale may be a
      reliable indicator of the degree of nausea and antiemetic efficacy.

PMID- 7820828
TI  - Safe handling of antineoplastic drugs. Results of a survey.
AB  - As research continues to highlight the risks involved in handling antineoplastic
      drugs, the health services are giving increased attention to safety measures. In
      order to establish what protective measures nursing staff employ and what they
      know about antineoplastic drugs, a survey was carried out in The Netherlands. The
      questions were based on the self-study modules by Dunne and the (American)
      Oncology Nursing Society. A total of 1,373 questionnaires were distributed in 10
      hospitals. Of these, 824 were returned, which represents a response rate of 60%.
      Over two-thirds (68%) of the nursing staff reported that they were involved, on a
      daily or weekly basis, in caring for patients being treated with antineoplastic
      drugs. In the view of 94% of the nurses, protective measures are effective. While
      administering antineoplastic drugs, 91% of the respondents said that they wore
      gloves, 21% said that they wore a gown, 18% wore a mask, and 3% used goggles.
      While handling excreta, fewer nurses applied safety measures. Thirty-nine percent
      of the respondents knew that latex gloves offer a greater degree of protection
      than PVC gloves. It appeared that there was not one Dutch hospital whose
      guidelines for the safe handling of antineoplastic material were completely up-to
      date and that nurses do not always follow the guidelines established.

PMID- 7820829
TI  - How well is your patient prepared for an MRI? An insider's perspective.
AB  - Often patients undergoing magnetic resonance imaging (MRI) for diagnostic
      purposes are not adequately prepared to deal with the claustrophobia commonly
      experienced while in the MRI machine. They may have been instructed on the
      procedure and some of the physical sensations they might encounter, but teaching
      about coping strategies to utilize when confronted with the occurrence of
      unanticipated claustrophobia when a sedating medication is not immediately
      available may often be lacking. Drawing on excerpts from a patient's journal that
      vividly describes her struggle to cope with claustrophobia during an MRI, this
      article discusses this commonly encountered experience within the context of
      theoretical perspectives of stress to underscore the importance of assessing for
      indications of rising anxiety. Suggestions for coping strategies to include in
      patient teaching are presented.

PMID- 7820830
TI  - Radiation therapy for oncological emergencies.

PMID- 7820831
TI  - Long-term results of percutaneous aspiration embolectomy.
AB  - PURPOSE: To evaluate percutaneous aspiration embolectomy (PAE) as a therapeutic
      alternative to surgical embolectomy. METHODS: Eighty-five patients underwent 90
      PAEs for embolic occlusions below the inguinal ligament between October 1987 and
      September 1992 in a prospective study with a 96% follow-up. RESULTS: The first
      PAE was clinically successful in 77 limbs (86%). In eight cases, major amputation
      was necessary. Eleven of 13 failures were observed in limbs with acutely
      threatening ischemia, but the success rate was independent of the time interval
      from embolism to the PAE procedure. The 30-day mortality rate was 3.5%. The
      cumulative primary patency rate at 1 and 4 years was 68% and 58%, respectively.
      The limb salvage rate was 88% after 1 year and 86% after 4 years. The patency
      rate was significantly better and the mortality was significantly lower in
      patients receiving long-term anticoagulation with coumadin. CONCLUSION: PAE is
      highly effective in the treatment of embolic occlusions of the lower leg arteries
      and should be considered as an alternative to Fogarty balloon embolectomy.

PMID- 7820832
TI  - Long-term follow-up of the Gunther basket inferior vena cava filter: does
      mechanical instability cause complications?
AB  - PURPOSE: The Gunther basket inferior vena cava filter (GBF) has been withdrawn
      from the market because of its mechanical instability, but a number of patients
      still live with the device. METHODS: In a two-center study, we evaluated the long
      term follow-up of the GBF, based on clinical data in 78 patients, and on imaging
      studies including plain radiographs, Doppler ultrasound, angiography, or computed
      tomography (CT) in 50 patients. RESULTS: In a mean period of 3 years, pulmonary
      embolism was diagnosed in five patients (6.4%), with an overall rate of 0.02
      embolic episodes per patient per year. None of these patients required
      hospitalization, and there were no deaths due to pulmonary embolism. Inferior
      vena cava thrombosis was documented in three patients (3.9%), and occlusive
      venous thrombosis at the access site in seven patients (9%). Spontaneous
      migration was documented in 43% of the examined filters and spontaneous
      disruption in 77%. Dislocated filter fragments were localized by CT in the
      adjacent retroperitoneum in 11%, in the aortic lumen in 2%, and in a peripheral
      pulmonary artery in 7%. None of the patients had symptoms attributable to filter
      migration or disruption. CONCLUSION: Our results indicate that the rate of
      clinically relevant complications with the GBF is no higher than with other vena
      cava filters. Because mechanical instability of the GBF had no clinical
      consequences, we conclude that patients who live with this device may be observed
      and treated in a manner similar to patients with other vena cava filters.

PMID- 7820833
TI  - Transfemoral liver biopsy by forceps: a review of 104 consecutive procedures.
AB  - PURPOSE: Transvenous liver biopsy is performed on patients with contraindications
      to percutaneous biopsy. Transfemoral liver biopsy has not been widely reported,
      and we present our experience of 104 consecutive procedures. METHODS: During a 30
      month period, 88 patients underwent 104 transfemoral liver biopsies. Under
      fluoroscopic guidance a 9 Fr curved introducer catheter is passed into the right
      hepatic vein via a standard femoral sheath. A 7 Fr biopsy forceps is then passed
      into the liver, opened and wedged. Prior to biopsy, the image intensifer is
      rotated so the relation of the capsular surface to the biopsy site is verified
      and capsular perforation avoided. RESULTS: Tissue samples obtained in 97 of 104
      procedures (93%) were adequate for diagnosis in 83 (80%). Complications occurred
      in six procedures (6%) including two capsular perforations; the latter two were
      treated by coil embolization. CONCLUSION: We found transfemoral liver biopsy
      using forceps to be a safe, well-tolerated procedure with a high diagnostic yield
      and it is a technically easy alternative to the transjugular approach using large
      needles.

PMID- 7820834
TI  - Percutaneous recanalization of recent renal artery occlusions: report of 10
      cases.
AB  - PURPOSE: Percutaneous recanalization of renal artery occlusion was attempted in
      10 patients. METHODS: All patients were hypertensive; before the procedure, the
      serum creatinine level was 80 mumol/L in one patient, ranged from 130-250 mumol/L
      in four patients, and was greater than 350 mumol/L in five, three of whom had
      anuria. Nine occlusions were thrombotic, one due to bilateral renal artery
      embolism. In four patients, percutaneous transluminal angioplasty of a
      contralateral renal artery occlusion was bilateral. In three patients,
      complementary local fibrinolysis was necessary. RESULTS: Three technical failures
      and one rethrombosis occurred after 24 h; in three of these cases the date of
      previous occlusion was unknown, whereas a relatively precise data was known for
      the seven other patients. One false aneurysm of the femoral artery was found 1
      month after the procedure. One patient, after six technical successes, died 5
      weeks after the procedure; follow-up for the other five was 6-36 months. Blood
      pressure was unchanged in four patients and improved in two. A significant and
      durable improvement of creatinine serum level (at least a 20% decrease) was
      observed in all six patients, usually after 1 month, thus enabling discontinuance
      of dialysis in three patients. CONCLUSION: Percutaneous recanalization should be
      proposed in cases of renal artery occlusion, especially to avoid terminal
      vascular azotemia and dialysis.

PMID- 7820835
TI  - Excess prevalence of supraaortic artery lesions in renovascular hypertension: an
      arteriographic study.
AB  - PURPOSE: High renin or renovascular hypertension (RVH) has been associated with a
      higher risk of stroke than low-to-normal renin hypertension. Our present purpose
      was to investigate the angiographic prevalence and distribution of lesions of the
      supraaortic arteries in a series of consecutive patients with RVH compared with
      control patients with low-to-normal renin primary hypertension (PH). METHODS:
      Thirty-two consecutive hypertensives (21 females, 11 males, aged 23-72 years)
      were investigated by renal and aortic arch digital subtraction arteriography
      (DSA). None of them had any history or symptoms of cerebrovascular disease. In
      each, the presence and severity of lesions at 17 different segments of the
      supraaortic arteries were evaluated and a score for supraaortic lesions was then
      calculated based on the number and severity of lesions. RVH was diagnosed in 16
      patients with renal artery stenoses and normalization of blood pressure after
      percutaneous transluminal renal angioplasty (PTRA) (n = 12) or surgery (n = 4).
      The cause of renal artery obstruction was fibrodysplasia in 5 patients (31%) and
      atherosclerosis in 11 (69%). PH was diagnosed in 16 patients based on a normal
      renal DSA and exclusion of all other possible causes of hypertension. RESULTS:
      The RVH and PH groups were similar with respect to age, sex, body mass index,
      diabetes, smoking habits, serum triglycerides, cholesterol, and blood pressure
      values, and differed only in plasma renin activity (6.0 +/- 1.7 ng AngI/ml/h in
      RVH vs. 1.4 +/- 0.3 in PH, mean +/- SEM, p = 0.008). The score for supraaortic
      arterial lesions was significantly higher in RVH than in PH (181 +/- 32 vs. 17 +/
      9, p = 0.001). This difference was also evident when the five patients with
      fibrodysplasia were compared with five age- and sex-matched PH patients. The
      sites most frequently involved were the carotid artery bulb and the internal
      carotid artery sinus. At each affected site the score was higher for RVH than for
      PH. CONCLUSION: For the same demographic features and risk profile, RVH was
      associated with a higher prevalence and severity of supraaortic artery lesions
      than PH.

PMID- 7820836
TI  - Percutaneous treatment of pulmonary hydatid cysts.
AB  - PURPOSE: To evaluate the safety and efficacy of percutaneous drainage of
      pulmonary hydatid cysts. METHODS: Eleven pulmonary hydatid cysts in eight
      patients were drained percutaneously after 1-2 years of treatment with
      mebendazole (50 mg/kg/day). Percutaneous needle aspiration was carried out under
      ultrasound (US) in six patients and computed tomography (CT) in two patients.
      Nine cysts were close to, and two cysts were distant from the thoracic wall.
      After aspiration, hypertonic (15%) saline solution was instilled for up to 35% of
      the estimated volume of the cyst and aspirated 5-10 min later. Follow-up ranged
      from 8 to 31 months (mean 16.3 months). RESULTS: Neither anaphylactic shock nor
      death occurred in any of the eight patients. One patient developed fever,
      ipsilateral hydropneumothorax, and contralateral pleural effusion. One patient
      suffered from fever, pneumothorax, and abscess and was treated surgically; one
      developed fever and dyspnea. The volume reduction during follow-up was 47%-93%.
      The cystic contents turned into a pseudotumor appearance with a thick irregular
      contour on CT and higher Hounsfield units. On US, the cysts showed a
      heterogeneous content with internal echoes representing detached and degenerated
      membranes, and the fluid content almost completely disappeared. CONCLUSION: We
      believe that percutaneous therapy of pulmonary hydatid disease is an effective
      alternative to surgical treatment in patients who have failed medical therapy.

PMID- 7820837
TI  - Bronchial arteriography and transcatheter embolization in the management of
      hemoptysis.
AB  - PURPOSE: The purpose of this study was to determine the factors influencing the
      effect of bronchial artery embolization in treating massive hemoptysis and the
      value of bronchial arteriography in the evaluation of patients with hemoptysis.
      METHODS: Thirty-five patients with acute hemoptysis were evaluated by means of
      bronchial arteriography and treated with transcatheter embolization. Specific
      causes for bleeding were bronchiectasis (17), lung cancer (9), tuberculosis (4),
      tetralogy of Fallot (1), and idiopathic hemoptysis (4). The materials used for
      embolization were gelatin sponge in 33 patients, dextran microspheres in 2, and
      stainless coils in 1. RESULTS: The angiographic signs of hemorrhage encountered
      were extravasation of contrast media (14.2%), hypervascularization (94.5%),
      bronchopulmonary shunts (34.2%), and bronchial artery aneurysms (14.2%).
      Immediate control of bleeding occurred in 32 (91.4%) of 35 patients after
      embolization. The rate of recurrent hemoptysis was 20.0% after 2 weeks of the
      procedure, but the hemorrhage was less severe than before treatment. CONCLUSION:
      The data suggest that bronchial artery embolization is an effective method for
      managing patients with hemoptysis. Minor bleeding recurrences appear to be
      relatively frequent.

PMID- 7820838
TI  - Flexible tantalum stents: effects in the stenotic canine urethra.
AB  - PURPOSE: Evaluate the effects of flexible tantalum stents (Strecker) implanted
      into stenotic canine urethras. METHODS: Eight conditioned, adult, German shepherd
      dogs, weighing 30-40 kg, were used. Strictures were created surgically in the
      bulbar urethra just proximal to the os penis. Two months postsurgery, strictures
      were documented radiographically and then balloon dilated. Following dilatation,
      a single Strecker stent was placed across the stricture. Stents were 7 mm in
      expanded diameter and either 2 or 4 cm in length. Retrograde urethrography was
      performed immediately after stent placement and then biweekly for up to 12
      months. Two dogs were sacrificed at 2, 4, 6, and 12 months post-stenting, and
      necropsy was performed. The urethra was excised, fixed, and examined by scanning
      electron and light microscopy. RESULTS: Clinical success was achieved without
      complications in all animals. Hyperplasia of the urothelium was noted 4-6 weeks
      after stent placement and was most pronounced at 4-6 months. Mucosal folds were
      found between the stent struts. Restenosis occurred at the distal end of the
      stent in one dog. Histological alterations were noted in the deeper layers of the
      urethral wall. CONCLUSION: Strecker stents were well tolerated in all animals and
      seem useful for the treatment of urethral strictures.

PMID- 7820840
TI  - Immediate transbiliary embolization of a biliary-hepatic artery fistula
      encountered during access for percutaneous biliary drainage.
AB  - The authors describe a case in which a biliary-hepatic artery fistula was created
      by a glidewire perforation during percutaneous transhepatic biliary drainage and
      was successfully treated by embolization via the transbiliary tract. Great
      caution should be exercised to avoid perforation when a Terumo hydrophilic
      glidewire is used during biliary intervention.

PMID- 7820839
TI  - Plasma treatment effects on the tantalum Strecker stent implanted in femoral
      arteries of sheep.
AB  - PURPOSE: To evaluate the effects of plasma treatment, a cleaning process for
      removal of organic contaminants from the knit-wire surface of tantalum Strecker
      stents, on biocompatibility and thrombogenicity. METHODS: A treated or untreated
      stent was randomly implanted in both femoral arteries of 15 sheep studied for
      periods of 4 (group 1), 15 (group 2), or 42 (group 3) days. Patency, histological
      changes, and mechanical effects were compared by means of radiologic and
      pathologic controls. RESULTS: Plasma treatment did not influence overall patency
      (93.3% vs 86.7%), maximal neointimal hyperplasia in groups 2 and 3 (801 +/- 123
      vs 733 +/- 179 microns), or media thinning in any group (254 +/- 92 vs 285 +/- 72
      microns), but modified the elastic properties of the stents by limiting (p =
      0.01) shortening at implantation. CONCLUSION: Plasma treatment does not affect
      the biocompatibility and thrombogenicity of Strecker stents implanted in normal
      femoral arteries of sheep but modifies their elastic properties. Further studies
      are needed to account for this effect.

PMID- 7820841
TI  - Chronic hepatic encephalopathy due to spontaneous splenorenal shunt: successful
      treatment by transhepatic shunt embolization.
AB  - A spontaneous splenorenal shunt, leading to chronic hepatic encephalopathy, was
      treated by transhepatic occlusion with coils and Enbucrylate. There were no
      complications. Hepatic encephalopathy subsided.

PMID- 7820842
TI  - Pseudoaneurysm of the common femoral vein as a late complication of right heart
      catheterization.
AB  - Complications following venous punctures are unusual. We describe a case of a
      false common femoral vein aneurysm following right heart catheterization in a
      patient with systemic venous hypertension due to tricuspid regurgitation. The
      initial interpretation of the Doppler ultrasound study lead to a digital
      subtraction femoral arteriogram which was normal. Magnetic resonance venography
      demonstrated a femoral venous pseudoaneurysm.

PMID- 7820843
TI  - Relationship between [Ca2+] changes in nucleus and cytosol.
AB  - The free calcium concentration in nucleus ([Ca2+]n) and in cytoplasm ([Ca2+]c) of
      single cells were estimated by confocal laser microscopy using the Ca(2+)
      indicator Indo-1. It is shown that in various cell types a nucleo-cytosolic
      Ca(2+)-gradient is present at rest and during stimulation. The direction and the
      extent of the nucleo-cytosolic Ca(2+)-gradient may vary with the cell type,
      differentiation status, phosphorylation conditions and also with the type of
      agonist. Evidence is given for the role of extra- and intranuclear storage sites
      as well as for Ca(2+)-influx. Finally potential artefactual interference with the
      measurements is discussed.

PMID- 7820844
TI  - Propagation of cytosolic calcium waves into the nuclei of hepatocytes.
AB  - The temporal and spatial organization of [Ca2+] changes within the nucleus of
      Fura-2 loaded hepatocytes maintained in primary culture has been investigated.
      Vasopressin stimulation induced oscillatory waves of cytosolic free [Ca2+]
      increase, which propagated freely through the nuclear region. Based on the
      amplitude of the Fura-2 signals from this region, the morphology of the
      hepatocyte nucleus and the rapid penetration of the nucleus by injected Fura-2,
      it can be concluded that the nuclear Ca2+ responses reflect changes occurring
      within the nucleoplasm. Intranuclear Ca2+ increases occurred as waves that appear
      to be directed by the Ca2+ waves passing through the surrounding cytoplasm. The
      apparent velocity of Ca2+ waves was higher in the nucleoplasm than in the
      cytoplasm (19.5 +/- 2.9 versus 11.0 +/- 1.1 microns/s). The nucleoplasm does not
      contain vesicular Ca2+ stores that might be released by Ins(1,4,5)P3. However,
      the nuclear envelope functions as a Ca2+ store that is sensitive to mobilization
      by Ins(1,4,5)P3. We conclude that the [Ca2+] in the nucleoplasm of the hepatocyte
      is close to equilibrium with the cytosolic [Ca2+] and that oscillatory waves of
      cytosolic [Ca2+] are closely paralleled by similar [Ca2+] changes in the
      nucleoplasm. The nuclear envelope is a component of the intracellular
      Ins(1,4,5)P3-sensitive Ca2+ storage pool and may serve as a reservoir for [Ca2+]
      elevations within the nucleus.

PMID- 7820845
TI  - Nuclear targeting of aequorin. A new approach for measuring nuclear Ca2+
      concentration in intact cells.
AB  - We here describe the measurement of nuclear Ca2+ concentration ([Ca2+]n) with
      targeted recombinant aequorin. Two aequorin chimeras have been constructed,
      composed of the Ca(2+)-sensitive photoprotein and two different portions of the
      glucocorticoid hormone receptor (GR). The shorter chimera (nuAEQ), which contains
      the nuclear localization signal (NLS) NL1 of GR, but lacks its hormone binding
      domain, HBD, is constitutively localized in the nucleus; the longer one
      (nu/cytAEQ), which contains both NLSs (NL1 + NL2) and the HBS of GR, is normally
      localized in the cytosol, but is translocated to the nucleus upon treatment with
      the hormone. When localized to the nucleus, both chimeras give the same estimates
      of [Ca2+]n, both at rest and upon stimulation with the InsP3 generating agonist
      histamine. The [Ca2+]n values appear very close, both at rest and upon
      stimulation, to those of the cytoplasm, measured with cytosolic recombinant
      aequorin, suggesting that, at least in this cell model, the nuclear membrane does
      not represent a major barrier to the diffusion of Ca2+ ions, and that the nucleus
      does not regulate its [Ca2+] independently from the cytosol.

PMID- 7820846
TI  - Calcium signals in and around the nucleus in sea urchin eggs.
AB  - A transient rise in cytoplasmic Ca2+ activity in the sea urchin egg occurs during
      fertilization due to calcium release from an intracellular store. Using a
      combination of the Ca2+ sensitive dye Calcium Green dextran and the Ca2+
      insensitive dye tetramethylrhodamine dextran we have obtained confocal ratio
      images of free cytoplasmic calcium distribution during the fertilization calcium
      wave. We can also trigger calcium release using calcium-releasing agonists such
      as InsP3, ryanodine and cADP-ribose. Calcium levels are in all cases similar
      within nucleus and in the cytoplasm. A striking result from confocal calcium
      imaging is that the fertilization calcium wave is not the only spatio-temporal
      calcium signal observed after fertilization. In fact, a second calcium wave
      propagates through the egg as pronuclear migration begins; this wave also
      originates at the point of sperm entry. A global calcium increase is also
      recorded during the fusion of the male and female pronuclei. We conclude that
      calcium concentrations in the nucleus are similar to those in the cytoplasm
      during these calcium transients, that a remnant at the point of sperm entry can
      originate a second propagating calcium wave and that a global calcium transient
      occurs at the time of pronuclear fusion.

PMID- 7820847
TI  - Nuclear calcium transport and the role of calcium in apoptosis.
AB  - The last decade has been the rapid development of research investigating the
      molecular mechanisms whereby hormones, peptide growth factors and cytokines
      regulate cell metabolism, differentiation and proliferation. One general
      signalling mechanism used to transfer the information delivered by agonists into
      appropriate intracellular compartments involves the rapid Ca2+ redistribution
      throughout the cell, which results in transient elevations of the cytosolic free
      Ca2+ concentration. Ca2+ signals are required for a number of cellular functions,
      including the activation of nuclear processes such as gene transcription and cell
      cycle events. The latter requires that appropriate Ca2+ signals elicited in
      response to agonists be transduced across the nuclear envelope. It has generally
      been assumed that small molecules, metabolites and ions could diffuse freely
      across the nuclear envelope. Nevertheless, several findings during the past few
      years have suggested that nuclear pore permeability can be regulated and that ion
      transport systems and ion-selective channels may exist in the nuclear membranes
      and regulate intranuclear processes. Intranuclear Ca2+ fluctuations can affect
      chromatin organization, induce gene expression and also activate cleavage of
      nuclear DNA by nucleases during programmed cell death or apoptosis. The possible
      mechanisms involved in nuclear Ca2+ transport and the regulation of nuclear
      Ca(2+)-dependent enzymes in apoptosis are discussed in the following sections.

PMID- 7820848
TI  - Calmodulin and calmodulin-binding proteins in the nucleus.

PMID- 7820849
TI  - The nuclear phosphoinositide cycle--does it play a role in nuclear Ca2+
      homoeostasis?
AB  - The probable answer to this question is no. Much of the current evidence
      summarised elsewhere in this issue points to nuclear Ca2+ changes changing in
      response to cytosolic Ca2+, with little evidence for an independently controlled
      nuclear Ca2+ homeostasis. There are InsP3 receptors in the nuclear membrane, and
      it is possible that during nuclear membrane assembly the InsP3 acting on these
      (Sullivan and Wilson, this issue) is formed by an inositide cycle located on the
      assembling nuclear skeleton. But our current experimental data suggest that when
      the nucleus is intact, InsP3 generated by this cycle would have to exit through
      the nuclear pores to act on any known InsP3 receptors. Thus the nuclear inositide
      cycle appears more likely to serve to generate diacylglycerol to activate protein
      kinase C, and/or to generate inositol phosphates such as InsP2, which may have
      distinct intranuclear functions.

PMID- 7820850
TI  - The nuclear inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate
      receptors.
AB  - IP3R is located to the inner nuclear membrane. Nuclear IP3R is recognized as a
      220 kD immunoreactive protein by antisera raised against purified rat brain IP3R.
      Antisera against C-terminal 95-108 peptide fragment derived from rat brain IP3R
      does not reveal immunoreactivity in the nucleus. Nuclear IP3R is sensitive to
      heparin and is phosphorylated by nuclear PKC, enhancing the efficiency of IP3 in
      nuclear calcium release. There are two IP4 binding sites located to the nuclear
      envelope. The nuclear IP4R is sensitive to pH and pH 6.5 is found optimum for the
      ligand binding. The high affinity IP4R is associated with the outer nuclear
      membrane and mediates nuclear calcium uptake by IP4. Low affinity IP4R is
      identified with the inner nuclear membrane and is not involved in IP4 mediated
      calcium entry into the nucleus. The nature of IP4R associated with the outer
      nuclear membrane as compared with the one identified with the inner nuclear
      membrane remains to be elucidated.

PMID- 7820851
TI  - A new role for IP3 receptors: Ca2+ release during nuclear vesicle fusion.
AB  - During nuclear assembly, vesicles derived from the mitotic disassembly of the
      nuclear membranes reform the nuclear envelope. The vesicles first bind to
      chromosomes, specifically recognize other nuclear vesicles and then fuse to
      enclose the chromosomes. The proteins that mediate these events are largely
      unknown. Using reconstituted extracts of Xenopus eggs, we found that nuclear
      vesicle fusion required elevated (microM) concentrations of free Ca2+ [Sullivan
      KMC. Busa WB. Wilson KL. (1993) Cell, 73, 1411-1422]. Our data suggest that Ca2+
      is released from the vesicle lumen by the activation of IP3 receptors (ligand
      gated Ca2+ channels). We propose that the role of IP3 receptors during nuclear
      assembly may be analogous to that of voltage-gated Ca2+ channels during regulated
      secretion: to provide a microdomain of high cytosolic Ca2+ that triggers fusion.
      In this article, we will briefly describe current ideas about nuclear assembly
      and disassembly, and summarize the evidence that IP3 receptors are required for
      nuclear vesicle fusion. We will discuss parallels between our results and the
      role of voltage-gated Ca2+ channels, and Ca2+, in regulated exocytosis. Finally,
      we will address the question of how IP3 receptors are activated during nuclear
      vesicle fusion: is there a signal that stimulates IP3 production, or is the
      channel activated directly?

PMID- 7820852
TI  - The role of calcium in cell division.
AB  - Calcium ions (Ca2+) appear to participate in the regulation of several aspects of
      cell division. Evidence is accumulating that transients or local gradients in the
      [Ca2+] contribute to different events including nuclear envelope breakdown and
      reformation, cleavage furrow formation and growth, and cell plate formation. At
      present there is little direct evidence that Ca2+ transients trigger the onset of
      anaphase. However, studies with exogenously applied Ca2+ indicate that spindle
      fibers and the movement of chromosomes at anaphase are exquisitely sensitive to
      the ion at physiological levels. Although Ca2+ is involved with many processes
      there are many gaps in our understanding, particularly pertaining to exactly when
      and where the ion concentration changes are expressed, which events and
      macromolecules are targeted, and what the processes are that control Ca2+.

PMID- 7820853
TI  - Calcium regulation of immediate-early response genes.
AB  - A rise in intracellular Ca2+ concentration induces the transcription of a number
      of eukaryotic genes through transcription factors interacting with calcium
      response elements. Immediate-early response genes encode proteins that couple
      extracellular signals to phenotypic alterations by modulating the transcription
      rates of target genes. Since the activation of early response genes occurs within
      minutes, this class of genes has served as a paradigm for the understanding of
      the molecular mechanisms by which external signals are conveyed to the nucleus to
      induce changes in genetic programs. In this review, we outline the recent
      information which has been gained specifically on how the Ca2+ messenger system
      modulates early response gene expression. We also discuss some lines of research
      with the intent of linking closer Ca2+ homeostasis and gene expression studies
      which in the past have followed their own separate routes.

PMID- 7820854
TI  - Sequential appearance of muscle-specific proteins in myoblasts as a function of
      time after cell division: evidence for a conserved myoblast differentiation
      program in skeletal muscle.
AB  - Based on the assumption that a conserved differentiation program governs the
      assembly of sarcomeres in skeletal muscle in a manner analogous to programs for
      viral capsid assembly, we have defined the temporal and spatial distribution of
      10 muscle-specific proteins in mononucleated myoblasts as a function of the time
      after terminal cell division. Single cells in mitosis were identified in
      monolayer cultures of embryonic chicken pectoralis, followed for selected time
      points (0-24 h postmitosis) by video time-lapse microscopy, and then fixed for
      immunofluorescence staining. For convenience, the myoblasts were termed x-h-old
      to define their age relative to their mitotic "birthdate." All 6 h myoblasts that
      emerged in a mitogen-rich medium were desmin+ but only 50% were positive for a
      alpha-actin, troponin-I, alpha-actinin, MyHC, zeugmatin, titin, or nebulin. By 15
      h postmitosis, approximately 80% were positive for all of the above proteins. The
      up-regulation of these 7 myofibrillar proteins appears to be stochastic, in that
      many myoblasts were alpha-actinin+ or zeugmatin+ but MyHC- or titin- whereas
      others were troponin-I+ or MyHC+ but alpha-actinin- or alpha-actin-. In 15-h-old
      myoblasts, these contractile proteins were organized into nonstriated myofibrils
      (NSMFs). In contrast to striated myofibrils (SMFs), the NSMFs exhibited variable
      stoichiometries of the sarcomeric proteins and these were not organized into any
      consistent pattern. In this phase of maturation, two other changes occurred: (1)
      the microtubule network was reorganized into parallel bundles, driving the
      myoblasts into polarized, needle-shaped cells; and (2) the sarcolemma became
      fusion-competent. A transition from NSMFs to SMFs took place between 15 and 24 h
      (or later) postmitosis and was correlated with the late appearance of myomesin,
      and particularly, MyBP-C (C protein). The emergence of one, or a string of
      approximately 2 mu long sarcomeres, was invariably characterized by the
      localization of myomesin and MyBP-C to their mature positions in the developing A
      bands. The latter group of A-band proteins may be rate-limiting in the assembly
      program. The great majority of myoblasts stained positively for desmin and
      myofibrillar proteins prior to, rather than after, fusing to form myotubes. This
      sequential appearance of muscle-specific proteins in vitro fully recapitulates
      myofibrillar assembly steps in myoblasts of the myotome and limb bud in vivo, as
      well as in nonmuscle cells converted to myoblasts by MyoD. We suggest that this
      cell-autonomous myoblast differentiation program may be blocked at different
      control points in immortalized myogenic cell lines.

PMID- 7820855
TI  - cAMP-induced morphological changes in an immortalized Schwann cell line: a
      prelude to differentiation?
AB  - Schwann cells (SC), the myelinating cells of the peripheral nervous system, show
      a remarkable capacity to switch from a differentiated state to a proliferative
      state both during development and peripheral nerve regeneration. In order to
      better understand the regulatory mechanisms involved with this change we are
      studying a Schwann cell line transfected with the SV-40 large T gene (TSC). Serum
      free medium combined with elevating intra-cellular cAMP levels produced a slower
      proliferating TSC whose morphology changed from pleiomorphic to process bearing,
      reminiscent of primary SC in culture. This change was abrogated by colcemid but
      was unaltered by cytochalasin D, indicating a major role for microtubules.
      Ultrastructural studies demonstrated numerous microtubules in the cellular
      extensions which correlated with strong immunocytochemical staining for tubulin
      in the processes. Analysis of cytoskeletal fractions from the treated cells
      revealed a greater proportion of tubulin in the polymerized state compared with
      untreated cells which closely resembled the distribution in primary SC. The
      cytoskeletal changes observed in the TSC as a result of elevating the intra
      cellular cAMP levels may reflect the earliest cellular changes in the induction
      of myelination.

PMID- 7820857
TI  - Differential localization of alpha-actinin and the 30 kD actin-bundling protein
      in the cleavage furrow, phagocytic cup, and contractile vacuole of Dictyostelium
      discoideum.
AB  - Dictyostelium discoideum amoebae possess eight different actin crosslinking
      proteins. Immunofluorescence microscopy has been employed in this study to
      investigate the intracellular localization of two of these proteins, alpha
      actinin and the 30 kD actin-bundling protein, to investigate whether they are
      redundant, or alternatively, make distinct contributions to cell structure and
      movement. The 30 kD protein is concentrated in the cleavage furrow of dividing
      cells, while enhanced staining for alpha-actinin is not apparent in this region.
      By contrast, alpha-actinin is concentrated around the contractile vacuole, while
      the 30 kD protein is not preferentially localized in the area of this organelle.
      Association of alpha-actinin with the contractile vacuole was confirmed by
      colocalization with calmodulin, a marker of this organelle. There are temporal
      differences in the localization of the 30 kD protein and alpha-actinin during
      phagocytosis. The 30 kD protein is localized in the phagocytic cup, but
      disassociates from phagosomes soon after internalization [Furukawa et al., 1992:
      Protoplasma 169: 18-27]. alpha-actinin enters the phagocytic cup after the 30 kD
      protein, and remains associated with the phagosome after the 30 kD protein has
      disassociated. These results support the hypothesis that alpha-actinin and the 30
      kD protein play distinct roles in cell structure and movement in Dictyostelium.

PMID- 7820856
TI  - Differential regulation of skeletal muscle myosin-II and brush border myosin-I
      enzymology and mechanochemistry by bacterially produced tropomyosin isoforms.
AB  - In this report, we have compared the physical properties and actin-binding
      characteristics of several bacterially produced nonmuscle and striated muscle
      tropomyosins, and we have examined the effects of these isoforms on the
      interactions of actin with two structurally distinct classes of myosin: striated
      muscle myosin-II and brush border (BB) myosin-I. All of the bacterially produced
      nonmuscle tropomyosins bind to F-actin with the expected stoichiometry and with
      affinities comparable to that of a tissue produced alpha-tropomyosin, although
      the striated muscle tropomyosin CTm7 has a lower affinity for F-actin than a
      tissue-purified striated muscle alpha tropomyosin. The bacterially produced
      isoforms also protect F-actin from severing by villin as effectively as tissue
      purified striated muscle alpha-tropomyosin. The bacterially produced 284 amino
      acid striated muscle tropomyosin isoform CTm7, the 284 amino acid nonmuscle
      tropomyosin isoform CTm4, and two chimeric tropomyosins (CTm47 and CTm74) all
      inhibit the actin-activated MgATPase activity of muscle myosin S1 by
      approximately 70-85%, comparable to the inhibition seen with tissue-purified
      striated muscle alpha tropomyosin. The 248 amino acid tropomyosin XTm4 stimulated
      the actin-activated MgATPase activity of muscle myosin S1 approximately two- to
      threefold. The in vitro sliding of actin filaments translocated by muscle myosin
      II (2.4 microns/sec at 19 degrees C, 5.0 microns/s at 24 degrees C) increased 25
      65% in the presence of XTm4. Tropomyosins CTm4, CTm7, CTm47, and CTm74 had no
      detectable effect on myosin-II motility. The actin-activated MgATPase activity of
      BB myosin-I was inhibited 75-90% by all of the tropomyosin isoforms tested,
      including the 248 amino acid tropomyosin XTm4. BB myosin-I motility (50 nm/s) was
      completely inhibited by both the 248 and 284 amino acid tropomyosins. These
      results demonstrate that bacterially produced tropomyosins can differentially
      regulate myosin enzymology and mechanochemistry, and suggest a role for
      tropomyosin in the coordinated regulation of myosin isoforms in vivo.

PMID- 7820858
TI  - Assembly and bundling of marginal band microtubule protein: role of tau.
AB  - Microtubule protein extracted from dogfish erythrocyte cytoskeletons by
      disassembly of marginal bands at low temperature formed linear microtubule (MT)
      bundles upon reassembly at 22 degrees C. The bundles, which were readily visible
      by video-enhanced phase contrast or DIC microscopy, increased in length and
      thickness with time. At steady state after 1 hour, most bundles were 6-11 microns
      in length and 2-5 MTs in thickness. No inter-MT cross-bridges were visible by
      negative staining. The bundles exhibited mechanical stability in flow as well as
      flexibility, in this respect resembling native marginal bands. As analyzed by SDS
      PAGE and immunoblotting, our standard extraction conditions yielded MT protein
      preparations and bundles containing tau protein but not high molecular weight
      MAPs such as MAP-2 or syncolin. In addition, late fractions of MT protein
      obtained by gel filtration were devoid of high molecular weight proteins but
      still produced MT bundles. The marginal band tau was salt-extractable and heat
      stable, bound antibodies to mammalian brain tau, and formed aggregates upon
      desalting. Antibodies to tau blocked MT assembly, but both assembly and bundling
      occurred in the presence of antibodies to actin or syncolin. The MTs were
      "unbundled" by subtilisin or by high salt (0.5-1 M KCl or NaCl), consistent with
      tau involvement in bundling. High salt extracts retained bundling activity, and
      salt-induced unbundling was reversible with desalting. However, reversibility was
      observed only after salt-induced MT disassembly had occurred. Reconstitution
      experiments showed that addition of marginal band tau to preassembled MTs did not
      produce bundles, whereas tau presence during MT reassembly did yield bundles.
      Thus, in this system, tau appears to play a role in both MT assembly and
      bundling, serving in the latter function as a coassembly factor.

PMID- 7820859
TI  - Fluorescence studies of spectrin and its subunits.
AB  - To better understand the solution structure of spectrin, the environment of its
      tryptophan residues have been examined by fluorescence spectroscopy. The spectra
      and the extent of quenching by several quenching agents have been determined for
      intact spectrin and its alpha and beta subunits. The arsenal of quenchers used in
      the study represented both hydrophilic and hydrophobic species including anionic,
      cationic and neutral compounds. Effects on spectrin fluorescence of ethanol and
      ionic strength, which extend and/or rigidify spectrin, and of glycerol, which is
      commonly used in electron microscopy of the protein, have also been assessed in
      the presence and absence of quenchers. Most of the tryptophans of spectrin are
      either internally quenched or are sequestered, hindering the approach of
      hydrophilic quenching agents. Both the spectral shape and the extent of quenching
      by acrylamide indicate that some tryptophans of the beta subunit are slightly
      more exposed in the isolated chain than in the dimer. Similar effects on spectra
      and on quenching of the intact dimer and of the isolated beta chain are seen when
      the ionic strength is reduced. Ethanol and glycerol reduce spectrin tryptophan
      accessibility to 2-p-toluidinyl napthalene-6-sulfonic acid (TNS). It therefore
      appears that low ionic strength, alpha-beta association and neutral solute (or
      lowered dielectric constant) all induce a similar, but modest conformational
      change in the domain structure. The extent of TNS binding is not increased by
      lowering the ionic strength, suggesting that the expansion and/or stiffening of
      the molecule in low electrolyte solution does not involve exposure of significant
      numbers of hydrophobic sites.

PMID- 7820860
TI  - Striated fibers in trichomonads: costa proteins represent a new class of proteins
      forming striated roots.
AB  - The production of monoclonal antibodies and the use of biochemical techniques
      revealed that B-type costa proteins in trichomonads are composed of several major
      polypeptides with molecular weight detected between 100 and 135 kDa similar to
      those found in the A-type costae. Although differences were observed between the
      two types in their fine structure, we tested whether proteins composing the two
      costa types belong to the same protein family. A polyclonal antibody produced
      against the 118 kDa costa protein of Trichomonas vaginalis also recognized a 118
      kDa costa protein in all other trichomonad genera studied so far whether they
      have A- or B-type costae. Moreover biochemical characteristics of costa proteins
      indicated that these proteins might represent a novel class of striated root
      forming proteins in addition to centrin, giardin, and assemblin.

PMID- 7820861
TI  - Microtubule associated protein MAP1A is an actin-binding and crosslinking
      protein.
AB  - High molecular weight microtubule-associated proteins MAP1A and MAP2 form thin
      projections from microtubule surfaces and have been implicated in crosslinking
      microtubules and other cytoskeletal components. We have purified native MAP1A
      from bovine brain and have studied its interaction with G- and F-actin. Using a
      solid-phase immunoassay we show that MAP1A binds in a dose-dependent manner to
      both G-actin and F-actin. Addition of MAP1A to F-actin causes gelation of F-actin
      and SDS-PAGE analysis shows that MAP1A co-sediments with the gelled network,
      under conditions where F-actin alone does not pellet. The low apparent viscosity
      of F-actin is markedly increased in the presence of MAP1A, suggesting that MAP1A
      can crosslink F-actin. Co-incubation experiments indicate that MAP1A and MAP2 may
      bind to common or overlapping sites on the actin molecule. The widespread
      distribution of MAP1A and its interaction with microtubules, actin, and
      intermediate filaments suggests that it may constitute an important determinant
      of neuronal and non-neuronal cellular morphology.

PMID- 7820863
TI  - Effects of 6-dimethylaminopurine on the length of the cell cycle and on the state
      of phosphorylation of putative intermediate filament proteins in sea urchin
      embryos.
AB  - The effects of 6-dimethylaminopurine (6-DMAP) on the length of the cell cycle and
      on the state of phosphorylation of a putative intermediate filament protein,
      p117, have been studied in sea urchin embryos. Embryos were transferred into sea
      water containing 600 microM 6-DMAP at 0.5, 2 or 5 min after insemination, and
      incubated for 30 or 90 min. The effects of 6-DMAP on cell cycle length were
      studied by determining the time required for completion of mitosis upon return of
      the embryos in normal sea water. In all instances, except for the embryos
      transferred 0.5 min after insemination (AI) and incubated for 30 min, the
      duration of the M phase was shortened compared to controls, being faster in the
      embryos incubated for 90 minutes compared to the 30 min incubation period.
      However, embryos transferred 0.5 min AI have a longer M-phase than those
      transferred 2 minutes or later after fertilization, suggesting that between 0.5
      and 2 min after fertilization, critical phosphorylating events occur which affect
      the commitment of the cells to enter M-phase. To study the pattern of p117
      phosphorylation during the cell cycle, the eggs were transferred 2 minutes after
      fertilization in presence of 600 microM 6-DMAP and with 200 microCi/ml of 32P
      orthophosphate. Analyses of 32P-labelled proteins after exposure of SDS-PAGE gels
      and their corresponding blots suggested that phosphorylation of p117 greatly
      increases at the time of pronuclear fusion, and then declines slightly at
      prophase-metaphase. This decrease is markedly enhanced when the cells are treated
      with 6-DMAP during metaphase in order to induce a premature breakdown of the
      mitotic apparatus. A causal link is suggested between the level of
      phosphorylation of p117 and its state of assembly.

PMID- 7820862
TI  - Microfilament-associated growth cone component depends upon Tau for its
      intracellular localization.
AB  - We report here a novel intracellular localization and function of Tau proteins in
      cultured cerebellar neurons. Immunofluorescence staining of detergent-extracted
      cytoskeletons with antibodies specific for Tau proteins revealed intense labeling
      of growth cone microtubules. Besides, suppression of Tau by antisense
      oligonucleotide treatment results in the complete disappearance of antigen 13H9,
      a specific growth cone component with properties of microfilament- and
      microtubule-associated protein [Goslin et al., 1989: J. Cell Biol. 109:1621
      1631], from its normal intracellular location. This phenomenon is unique to
      neurite-bearing cells, is not associated with the disappearance of microtubules
      from growth cones, and is not reversed by taxol, a microtubule-stabilizing agent.
      In addition, Tau-suppressed neurons display a significant reduction in growth
      cone area and fillopodial number; on the contrary, fillopodial length increases
      significantly. The alterations in growth cone morphology are accompanied by
      considerable changes in the phalloidin staining of assembled actin. Taken
      together, the present results suggest that in developing neurons Tau proteins
      participate in mediating interactions between elements of the growth cone
      cytoskeleton important for maintaining the normal structural organization of this
      neuritic domain.

PMID- 7820864
TI  - A model of flagellar and ciliary functioning which uses the forces transverse to
      the axoneme as the regulator of dynein activation.
AB  - Ciliary and flagellar motion is driven by the dynein-tubulin interaction between
      adjacent doublets of the axoneme, and the resulting sliding displacements are
      converted into axonemal bends that are propagated. When the axoneme is bent in
      the normal beating plane, force develops across the axoneme in the plane of the
      bend. This transverse force (t-force) has maximal effect on the interdoublet
      spacing of outer doublets 2-4 on one side of the axoneme and doublets 7-9 on the
      opposite side. Episodes of sliding originates as the t-force brings these
      doublets into closer proximity (allowing dynein bridges to form) and are
      terminated when these doublets are separated from each other by the t-force. A
      second factor, the adhesive force of the dynein-tubulin attachments (bridges),
      also acts to pull neighboring doublets closer together. This force resists
      termination of a sliding episode once initiated, and acts locally to give the
      population of dynein bridges a type of excitability. In other words, as bridges
      form, the probability of nearby bridges attaching is increased by a positive
      feedback exerted through the interdoublet spacing. A conceptual working
      hypothesis explaining the behavior of cilia and flagella is proposed based on the
      above concepts. Additionally, the feasibility of this proposed mechanism is
      demonstrated using a computer simulation. The simulation uses a Monte Carlo-type
      algorithm for dynein attachment and adhesive force, together with a geometric
      evaluation of the t-force on the key microtubule pairs. This model successfully
      develops spontaneous oscillations from any starting configuration (including a
      straight position). It is compatible with the physical dimensions, mechanical
      properties and bridge forces measured in real cilia and flagella. In operation,
      it exhibits many of the observed actions of cilia and flagella, most notably wave
      propagation and the ability to produce both cilia-like and flagella-like
      waveforms.

PMID- 7820865
TI  - Kinesin-related polypeptide is associated with vesicles from Corylus avellana
      pollen.
AB  - A 100-kDa polypeptide with microtubule-interacting properties was identified in a
      Golgi vesicle-enriched fraction from Corylus avellana pollen. The k71s23 antibody
      (directed to the kinesin heavy chain from bovine brain) [Tiezzi et al., 1992:
      Cell Motil. Cytoskeleton 21:132-137] localized the polypeptide on the external
      surface of membrane-bounded organelles. Some 100-kDa-containing vesicles
      copelleted with microtubules (polymerized from purified bovine brain tubulin)
      either in presence or absence of 5 mM AMPPNP, but they could be released by 10 mM
      ATP or 0.5 M KCl. The pollen microtubule-interacting protein, salt-extracted from
      membranes and partially purified by gel filtration, exhibited an ATPase activity
      (16.2 nmolPi/mg/min) which could be stimulated about 2-fold (32.5 nmolPi/mg/min)
      by addition of bovine brain microtubules. We suppose that the 100-kDa polypeptide
      is part of a molecular complex showing properties of the kinesin class.

PMID- 7820866
TI  - Localization of NuMA protein isoforms in the nuclear matrix of mammalian cells.
AB  - Using a monoclonal antibody 2D3 generated against a kinetochore-enriched human
      chromosome preparation, we identified a high molecular mass protein with nuclear
      staining in interphase and polar staining of the pericentriolar region in the
      mitotic spindle. Initially termed centrophilin, this protein associates with the
      minus-ends of spindle microtubules (MT) and appears to be important in spindle
      organization [Tousson et al., 1991: J. Cell Biol. 112:427-440]. Comparison of a
      partial cDNA sequence obtained for centrophilin with the full length cDNA
      sequence of nuclear mitotic apparatus protein (NuMA) [Compton et al., 1992: J.
      Cell Biol. 116:1395-1408; Yang et al., 1992: J. Cell Biol. 116:1303-1317] has
      indicated that NuMA and centrophilin are the same protein. Using a polyclonal
      NuMA antibody, we have provided further evidence that NuMA exists as isoforms as
      shown by peptide mapping and immunoblots. Sequential fractionation experiments
      along with immunofluorescence, immunoblotting, and EM immunogold labeling have
      demonstrated that NuMA isoforms are novel components of nuclear core filaments.
      Thus, NuMA, a long coiled-coil protein, appears to have dual functions in
      interphase and mitosis during the cell cycle. In interphase, NuMA likely plays a
      structural role in the nucleoskeleton that may be important in nuclear
      organization and functions, whereas in mitosis, NuMA appears to be associated
      with spindle MT organization and chromosome positioning.

PMID- 7820867
TI  - Nanometer scale vibration in mutant axonemes of Chlamydomonas.
AB  - Flagellar axonemes of sea urchin sperm display high frequency (200-400 Hz)
      vibration with nanometer scale amplitudes in the presence of ATP [Kamimura and
      Kamiya, 1992: J. Cell Biol. 116:1443-1454]. To investigate how various axonemal
      components affect the vibration, we examined vibration in wild-type and mutant
      axonemes of Chlamydomonas. At 1 mM ATP, wild-type axonemes underwent vibration at
      100-650 Hz with amplitudes of 4-40 nm. This vibration was similar to, but less
      regular than, that in sea urchin sperm. Axonemes of the mutants ida1 and ida4
      lacking part of the inner arm dynein underwent vibrations indistinguishable from
      that of wild-type. The mutant oda1 lacking the entire outer arm underwent
      vibration at about half the wild-type frequency. Unexpectedly, the paralyzed
      mutants pf18 lacking the central pair and pf14 lacking the radial spokes
      displayed vibration with significantly higher frequencies and smaller amplitudes
      than those in the wild-type vibration. These results indicate that the high
      frequency vibration is common to many kinds of mutant axonemes that lack various
      axonemal substructures, but that its manner is sensitive to the presence of outer
      arm dynein and the central pair/radial spoke system. Simultaneous measurements of
      amplitude and frequency in wild-type and mutant axonemes suggest that the
      velocity of microtubule sliding in vibrating axonemes is lower than the velocity
      of sliding under load-free conditions. The velocity is particularly low in
      pf18.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7820868
TI  - Intermittent swimming in the spermatozoa of the lugworm Arenicola marina (L.)
      (Annelida: Polychaeta).
AB  - Motile spermatozoa of the polychaete Arenicola marina were observed to swim
      intermittently. On the basis of the behaviour of the flagellum, the quiescent
      periods can be classified into two main types. The first are those in which,
      although the generation of the flagellar wave appears to be initiated, its
      passage down the axoneme appears blocked. This results in the formation of an
      acute bend (of approximately 2.65 rad) in the proximal region of the flagellum
      with the remainder of the axoneme remaining straight. These have been termed Type
      I quiescent periods and are very similar to the "cane-shaped" configuration which
      has been described in the spermatozoa of some sea urchins. Sperm may also enter a
      Type II quiescent period, in which both the propagation and the generation of
      flagellar waves appears blocked. The flagellum of such sperm appears straight or
      slightly curved and they can remain in this configuration for several minutes.
      With increased intensity and duration of irradiation, the length of time spent in
      Type II quiescent period was increased significantly. Both types of quiescent
      period were (1) reduced in duration and frequency by deletion of calcium from
      artificial sea water (ASW); (2) either abolished or reduced in duration by the
      addition of 1 mM cadmium chloride to ASW. In addition, flagellar waveforms very
      similar to those displayed by spermatozoa in Type I quiescent periods could be
      induced (if only for a short time) by the addition of the divalent cation
      ionophore A23187 to ASW.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7820869
TI  - Novel touch-induced, Ca(2+)-dependent phobic response in a flagellate green alga.
AB  - The biflagellate green alga Spermatozopsis similis exhibits a remarkable
      avoidance reaction in addition to the photophobic or stop response characteristic
      of such algae. S. similis normally swims forward with its anteriorly attached
      flagella directed posteriorly and propagating sine-like waves base to tip. Upon
      contact with surfaces or other cells, S. similis responds with rapid backward
      swimming, covering distances of up to 50 microns in 140 to 220 msec. This
      reaction, which we term the mechanoshock response, also can be triggered by
      vigorous mechanical stimulation, but not by physiological light intensities. It
      consists of 3 phases: (1) a rapid acceleration phase with average duration of 31
      msec; (2) a phase of about 66 msec with constant high speed (maximal velocities
      of > 600 microns.sec-1) or slow deceleration; and (3) a deceleration phase of
      approximately 83 msec, followed by a stop or short period of circling. The cells
      then resume forward swimming in a random direction. Prior to the mechanoshock
      response the flagella rapidly are brought together into a close parallel
      configuration extending anteriorly of the cell body. They then appear to propel
      the cell by undulatory beating, while the cell describes a pronounced helical
      path. Small decreases in the extracellular Ca2+ concentration, as well as low
      concentrations of Ba2+, strongly suppress the probability of this phobic
      reaction. We conclude that this mechanoshock response involves large Ca2+
      influxes, probably mediated by mechanosensitive and/or stretch-activated ion
      channel(s).

PMID- 7820870
TI  - Novel actin rods appeared in spores of Dictyostelium discoideum.
AB  - When spores of Dictyostelium discoideum matured through normal development were
      stained with rhodamine-phalloidin, rod-shaped fluorescence was found across the
      nucleus and in the cytoplasm. Electron micrographs of the rod shape showed that
      it consisted of long and straight fibers 12 nm in diameter. In contrast, a
      conventional actin rod, which usually is formed under stress conditions, is
      composed of short filaments 6 nm in diameter, and cannot be stained with
      fluorescent phalloidin. Hence it can be inferred that the structure appeared in
      Dictyostelium spores under no stress conditions is a novel actin rod.

PMID- 7820871
TI  - GDP inhibits the activity of the centrosome to nucleate microtubules.
AB  - Microtubule-nucleating ability of the centrosome in the isolated mitotic
      apparatus was investigated under the condition that the centrosomal fragment was
      preincubated with guanine nucleotides or its derivatives. GTP and non
      hydrolyzable GTP analogues such as GTP-gamma S or GMP-PNP consistently supported
      high activity of the centrosome to nucleate microtubules. On the other hand, GDP
      substantially suppressed the microtubule-nucleating activity of the centrosomes.
      Evidence has been presented that this is not simply due to the inhibitory effect
      of GDP on microtubule assembly. This result is consistent with the idea that GTP
      binding proteins such as 51 kDa protein and gamma-tubulin localized to the
      pericentriolar materials in the centrosome are competent for the nucleation of
      microtubules when it is saturated with GTP.

PMID- 7820872
TI  - Behaviour of the germ cell specific lamin through mammalian spermatogenesis as
      probed with monoclonal antibodies.
AB  - We had earlier identified a 60 kDa nuclear lamin protein (lamin(g)) unique to the
      germ cells of rat testis which was subsequently shown to be antigenically
      conserved in germ cells of grasshopper, rooster, frog and plants. We have now
      obtained eight monoclonal antibodies in mouse against this lamin(g) antigen.
      While all the eight Mabs reacted with lamin(g) antigen in an immunoblot analysis,
      only three Mabs (A11C7, A11D4, C1F7) showed strong reactivity in the
      immunofluorescence analysis of the germ cells. The Mabs A11C7 and A11D4 showed a
      slight cross-reactivity with rat liver lamin B. Indirect immunofluorescence
      analysis of pre-meiotic, meiotic and post-meiotic germ cells with Mabs have shown
      that while the lamin(g) is localized in the lamina structures of spermatogonia
      and round spermatids, it is localized to the phase dense regions of pachytene
      spermatocytes which is in conformity with our previous observations using rabbit
      polyclonal antibodies. The localization of the antigen in the germ cells was also
      confirmed by immunohistochemical staining of the thin sections of seminiferous
      tubules. By immunostaining the surface spread pachytene spermatocytes, the
      antigen was further localized to the telomeric ends of the paired homologous
      chromosomes. Using anti-somatic lamin B antibodies, we have also demonstrated the
      absence of somatic lamins in meiotic and post-meiotic germ cells. The lamina
      structure of pre-meiotic spermatogonial nucleus contains both somatic lamin B and
      lamin(g) as evidenced by immunofluorescence studies with two differently
      fluorochrome labelled anti-lamin B and anti-lamin(g) antibodies. The selective
      retention of lamin(g) in the pachytene spermatocytes is probably essential for
      anchoring the telomeric ends of the paired chromosomes to the inner nuclear
      membrane.

PMID- 7820873
TI  - Increased mRNA for CD63 antigen in atherosclerotic lesions of Watanabe heritable
      hyperlipidemic rabbits.
AB  - To identify a set of mRNAs that increases with the progression of
      atherosclerosis, differential hybridization screening of a cDNA library,
      constructed from total RNA in aortae of Watanabe heritable hyperlipidemic (WHHL)
      rabbits, was carried out. Here we report that one of the positive clones encodes
      a rabbit homologue of human CD63 antigen. Nucleotide sequence analysis of the
      cDNA revealed the primary structure of rabbit lysosomal membrane antigen CD63.
      Analysis of the mRNA by in situ hybridization revealed that a significant amount
      of the mRNA is accumulated in atherosclerotic lesions of WHHL rabbits. Northern
      blot analysis of total RNA prepared from aortae of WHHL and normal rabbits
      indicates that expression of the mRNA increased with age in WHHL rabbits,
      suggesting that expression of the mRNA is correlated with the progression of
      atherosclerosis.

PMID- 7820874
TI  - Differential susceptibility of morphologically TPA-resistant and -sensitive
      Balb/c 3T3 variants to TPA-induced cell transformation: relationship to induction
      of membrane ruffling.
AB  - To investigate the responsiveness to phorbol ester-mediated malignant cell
      transformation of Balb/c 3T3 variant clones that were morphologically phorbol
      ester-sensitive and -resistant, we used an in vitro two-stage transformation
      assay in which cells were treated with 0.1 microgram/ml of MCA as an initiator
      and subsequently with 12-O-tetradecanoylphorbol-13-acetate (TPA) as a promoter.
      The morphologically TPA-sensitive variant, TR5, and the parent cells showed a
      relatively low sensitivity to TPA-induced cell transformation, whereas the
      morphologically TPA-resistant variant, TR4 cells, exhibited 50- to 100-fold
      higher sensitivity to phorbol ester-induced cell transformation than the parent
      or the TR5 cells. We investigated the effects of TPA on protein kinase C
      activity, 80 kDa PKC substrate phosphorylation, the organization of actin stress
      fibers, DNA synthesis, and anchorage-independent growth in the three cell clones.
      They showed similar responses to these biological and biochemical events,
      indicating that these PKC-mediated events may not be the causes of the
      differential responsiveness of the variant cells to TPA-induced cell
      transformation. We further examined their responsiveness to growth factor
      mediated and spontaneous induction of membrane ruffling. When these cells were
      stimulated by PDGF in their growing phase, membrane ruffling was rapidly induced
      in the three cells. However, the PDGF-mediated membrane ruffling was completely
      suppressed in parent and TR5 but not TR4 cells in the confluent, contact
      inhibited (steady-state) growth phase. Similar responses were observed by other
      growth factors such as insulin, IGF-I, acidic or basic FGF. In addition, when the
      cells were cultured beyond confluence in the presence of TPA, spontaneous
      membrane ruffling was induced continuously up to termination of culture in TR4
      but not in parent and TR5 cells. These results suggest that the deficiency in
      cell contact-mediated inhibition of membrane ruffling may be responsible for
      hypersensitivity of TR4 cells to TPA-induced cell transformation.

PMID- 7820875
TI  - Selective inhibition of a step of myotube formation with wheat germ agglutinin in
      a murine myoblast cell line, C2C12.
AB  - Myoblast cells, C2C12, which is an established cell line from satellite cells of
      skeletal muscle of C3H mouse, start to fuse and form multinucleated cells
      (myotubes) and begin to express creatine phosphokinase and myosin, when culture
      medium is changed from the growth medium to the differentiation medium. Among the
      12 lectins that we tested, wheat germ agglutinin apparently suppressed the
      myotube development judged by phase-contrast microscopy, but did not affect the
      induction of creatine phosphokinase activity. The addition of N-acetylglucosamine
      or N,N',N"-triacetylchitotriose, which is a specific ligand for wheat germ
      agglutinin, to the differentiation medium, recovered this apparently suppressive
      effect of wheat germ agglutinin on the myotube development. Tachypleus
      tridentatus (Japanese horseshoe crab) lectin that specifically recognizes N
      acetylneuraminic acid, one of the sialic acids, showed no effect on the myotube
      development. It was suggested that wheat germ agglutinin suppressed the process
      through recognizing N-acetylglucosamine containing sugar. Surprisingly, even in
      the presence of wheat germ agglutinin, the ratio of mononucleated cell numbers to
      the genomic DNA content, which represents the fusion level, decreased after
      incubation in the differentiation medium, indicating that even when wheat germ
      agglutinin was present in the medium, cell fusion, which is the initial step of
      the myotube formation, occurred. Immunostaining with anti-skeletal muscle myosin
      antiserum confirmed that the myosin expressing cells actually fused and formed
      multinucleated cells. Their shape, however, was thin compared to that in the
      absence of wheat germ agglutinin. We propose that the membrane fusion step to
      form myotubes is composed of two distinct steps in C2C12; one fusion step is to
      form long and thin myotubes from mononucleated cells and the other one is to
      develop fat myotubes. Wheat germ agglutinin specifically inhibits the latter
      fusion step.

PMID- 7820876
TI  - Redistribution of synapsin I and synaptophysin in response to electrical
      stimulation in the rat neurohypophysial nerve endings.
AB  - To understand the dynamics of synaptic vesicles and synapsin I, we have studied
      the localization of synapsin I and synaptophysin in resting and stimulated nerve
      endings by ultracryomicrotomy and colloidal gold-immunocytochemistry. First, we
      characterized microvesicles in resting nerve endings of the rat neurohypophysis,
      which was chosen as the model of nerve ending in this study. Synaptophysin was
      localized in microvesicles that were clustered beneath the plasma membrane. Quick
      freeze deep-etching electron microscopy showed that short strands cross-linked
      microvesicles to each other, which highly resemble the structures observed in our
      studies of the presynaptic nerve terminals of central and peripheral nervous
      system and in vitro reconstitution of synapsin I and synaptic vesicles.
      Immunocytochemistry showed that synapsin I was localized to the region of cluster
      of microvesicles. Second, using this system, we examined localization of synapsin
      I and synaptophysin in nerve endings after electrical stimulation. Besides
      release of neurosecretory granules, clusters of microvesicles dissappeared and
      both microvesicles and synaptophysin were scattered over nerve endings. These
      changes were also confirmed by quick-freeze, freeze-substitution.
      Immunocytochemistry of the stimulated sample revealed that synapsin I was also
      scattered. The results show that microvesicles in neurohypophysis have similar
      characteristics of typical synaptic vesicles and synapsin I has a role as a
      scaffold to cross-link microvesicles to be clustered in resting nerve endings.
      This scaffold of synapsin I was disengaged after stimulation to redistribute
      microvesicles and synapsin I itself, which may be the mechanism of synapsin I to
      regulate the availability of synaptic vesicles for release.

PMID- 7820877
TI  - Extrahepatic bioactivation of aflatoxin B1 in fetal, infant and adult rats.
AB  - Whole-body autoradiography of 3H-labelled aflatoxin B1 (3H-AFB1) in female non
      pregnant adult and infant Sprague-Dawley rats showed retention of tissue-bound
      radioactivity, in addition to the liver, in the mucosa and some glands in the
      nose, and in the mucosa of the nasopharynx, trachea, bronchioles, colon and
      caecum. The extrahepatic binding was most pronounced in the infant rats. In a rat
      pretreated with the glutathione (GSH)-depleting agent phorone, bound labelling
      was also seen in the superficial part of the mucosa of the glandular stomach.
      Autoradiography of 3H-AFB1 in pregnant rats showed a marked localization of bound
      AFB1-metabolites in the fetal nasal olfactory and tracheal mucosa. In vitro
      experiments demonstrated that the nasal olfactory mucosa had a much higher
      capacity than the liver to form AFB1-metabolites which bound to DNA and protein.
      The bioactivation was observed both pre- and post-natally and increased with age.
      Bioactivation was found also in the caecum, the colon and the lateral nasal gland
      (Steno's gland), but not in the small intestine, oesophagus or Harderian gland.
      Our results indicated that glutathione-S transferase activity catalysing the AFB1
      8,9-epoxide GSH-conjugation was present in the nasal olfactory mucosa and liver
      at all pre- and post-natal ages examined. Several of the extrahepatic tissues
      able to bioactivate AFB1 have been reported to be targets for the carcinogenicity
      of the substance. Our results indicate that the extrahepatic carcinogenicity of
      AFB1 is correlated to a local bioactivation in the sensitive tissues.

PMID- 7820878
TI  - DNA strand breaking by the carbon-centered radical generated from 4
      (hydroxymethyl) benzenediazonium salt, a carcinogen in mushroom Agaricus
      bisporus.
AB  - 4-(Hydroxymethyl)benzenediazonium salt (HMBD), a carcinogen in mushroom Agaricus
      bisporus, was found to generate a carbon-centered radical, 4
      (hydroxymethyl)phenyl radical, during incubation at pH 7.4 and 37 degrees C, when
      estimated by Electron Spin Resonance (ESR) spin-trapping technique using 5,5
      dimethyl-1-pyrroline N-oxide (DMPO), N-tert-butylphenyl-alpha-nitrone (PBN) and
      3,5-dibromo-4-nitrosobenzene sulfonate (DBNBS). Formation of a substantial amount
      of benzyl alcohol during incubation of HMBD in the presence of a hydrogen donor,
      ethanol, supported the generation of the carbon-centered radical. When plasmid
      supercoiled DNA was incubated with HMBD at pH 7.4 and 37 degrees C for 30 min,
      the supercoiled DNA was converted into a nicked circular relaxed form and
      subsequently into a linear form. Sequence analysis indicated that the compound
      cleaved the plasmid DNA strand non-specifically. The intracellular double
      stranded DNA of Escherichia coli was fragmented by the compound, which may be
      responsible for its cytotoxicity. The compound induced mouse micronucleated
      peripheral reticulocytes. The compound was active in breaking DNA strands in the
      absence of molecular oxygen and in the presence of superoxide dismutase and
      catalase, indicating that no oxygen-derived radicals participated in the
      breaking. DNA breaking was inhibited by hydrogen donors butyl hydroxyanisole and
      ethanol, thiol compounds L-cysteine and 2-mercaptoethanol, and spin-trapping
      agents DMPO and PBN, indicating the direct contribution of the carbon-centered
      radical to the breaking.

PMID- 7820879
TI  - Desferal prevents against cell lysis induced by hydrogen peroxide to hypoxic
      hepatocytes: a role for free iron in hypoxia-mediated cellular injury.
AB  - Isolated hepatocytes incubated under hypoxic conditions were more sensitive to
      H2O2-mediated injury as compared to cells kept under aerobic conditions, but only
      for the highest H2O2 concentration tested (8 mM). At lower concentrations (2 and
      4 mM) cells were still able to detoxify H2O2 even under hypoxic conditions.
      Reoxygenation of hypoxic hepatocytes did not result in a cytolytic effect,
      whereas reoxygenation in the presence of H2O2 resulted in an enhanced
      cytotoxicity. The duration of previous hypoxia (before H2O2 addition) did not
      affect the lytic effect induced by H2O2. Enzymatic activities of both catalase
      and glutathione peroxidase were unchanged over 2 h of incubation under hypoxic
      conditions. Preincubation of hepatocytes in the presence of Desferal (5 mM)
      resulted in the abolition of H2O2-mediated lytic effects. A role for free iron,
      released from intracellular stores and acting on H2O2 to yield reactive oxygen
      species is discussed.

PMID- 7820880
TI  - Different metabolic pathways of 2,5-difluoronitrobenzene and 2,5
      difluoroaminobenzene compared to molecular orbital substrate characteristics.
AB  - The in vivo metabolite patterns of 2,5-difluoroaminobenzene and of its
      nitrobenzene analogue, 2,5-difluoronitrobenzene, were determined using 19F NMR
      analysis of urine samples. Results obtained demonstrate significant differences
      between the biotransformation patterns of these two analogues. For the
      aminobenzene, cytochrome P450 catalysed aromatic hydroxylation presents the main
      metabolic pathway. 2,5-Difluoronitrobenzene was predominantly metabolised through
      glutathione conjugation leading to excretion of 5-fluoro-2-(N-acetylcysteinyl)
      nitrobenzene and fluoride anions, and, to a minor extent, through cytochrome P450
      catalysed hydroxylation and nitroreduction. Pretreatment of the rats with various
      inducers of cytochrome P450 enzymes, known also to influence glutathione S
      transferase enzyme patterns, followed by exposure to the 2,5-difluoroamino- or
      2,5-difluoronitrobenzene, generally resulted in metabolite patterns that varied
      only to a small (< or = 12%) extent. Based on these results it was concluded that
      the biotransformation enzyme pattern is not the predominant factor in determining
      the metabolic route of these two model compounds. Additional in vitro microsomal
      and cytosolic incubations with 2,5-difluoroaminobenzene and 2,5
      difluoronitrobenzene qualitatively confirmed the in vivo results. NADPH/oxygen
      supported microsomal cytochrome P450 catalysed hydroxylation was observed only
      for 2,5-difluoroaminobenzene whereas cytosolic GSH conjugation occurred only in
      incubations with 2,5-difluoronitrobenzene as the substrate. Outcomes from
      molecular orbital calculations provided a working hypothesis that can explain the
      difference in metabolic pathways of the nitro- and aminobenzene derivative on the
      basis of their chemical characteristics. This hypothesis states that the chances
      for a nitro- or aminobenzene derivative to enter either a cytochrome P450 or a
      glutathione conjugation pathway are determined by the relative energy levels of
      the frontier orbitals of the compounds. The aminobenzene derivative has
      relatively high energy molecular orbitals leading to an efficient reaction of its
      highest occupied molecular orbital (HOMO) with the singly occupied molecular
      orbital of the cytochrome P450 (FeO)3+ intermediate, but a low reactivity of its
      lowest unoccupied molecular orbital (LUMO) with the HOMO of glutathione. The
      nitrobenzene, on the other hand, has molecular orbitals of relatively low energy,
      explaining the efficient interaction, and, thus, reaction between its LUMO and
      the HOMO electrons of glutathione, but resulting in low reactivity with the SOMO
      electron of the cytochrome P450 (FeO)3+ reaction intermediate.

PMID- 7820881
TI  - Studies on the effect of sulfite on benzo[a]pyrene-7,8-dihydrodiol activation to
      reactive intermediates in human polymorphonuclear leukocytes.
AB  - Sodium sulfite, a hydrolysis product of the environmental pollutant sulfur
      dioxide increased the activation of (-)-trans-7,8-dihydroxy-7,8
      dihydrobenzo[a]pyrene (BP-7,8-diol) to the (+)-anti-enantiomer of trans-7,8
      dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) in phorbol
      myristate acetate (PMA)-stimulated human polymorphonuclear leukocytes (PMNs).
      This effect was potentiated in the presence of DMSO. No significant effect of
      sulfite on BP-7,8-diol activation was observed in resting leukocytes. As revealed
      by the 32P-postlabelling technique the dominant adduct in both intracellular DNA
      and to DNA added to the leukocytes was (+)-anti-BPDE bound to the exocyclic
      nitrogen of deoxyguanosine. The mechanism underlying the stimulatory effect of
      sulfite on diol epoxide production and increased DNA-binding probably involves
      one-electron oxidation of sulfite to a sulfur trioxide radical anion and
      subsequent reaction with molecular oxygen to form the corresponding peroxyl
      radical. This step obviously requires PMA-initiated oxidative burst and thus,
      production of superoxide radical anions (O2-.).

PMID- 7820882
TI  - Some basic properties of ascorbate-dependent antioxidative-defence factors from
      rat liver cytosol.
AB  - Properties of the ascorbate-dependent antioxidative-defence factors from rat
      liver cytosol (Antonenkov and Sies, 1992, Biol. Chem. Hoppe-Seyler 373, 1111
      1116) were investigated. The factors are assayed by their capacity to inhibit
      Fe/ADP-ascorbate (nonenzymatic) lipid peroxidation. Ammonium sulfate
      fractionation and gel-filtration of the dialysed cytosol on Sephadex G-200 or
      Sephacryl S-400 led to the separation of factors A and B, with approximate
      molecular masses of > 400 kDa and 60 kDa, respectively. After fractionation of
      cytosol, factors A and B required the presence of the thiol- reducing agent,
      dithioerythritol, for their activity; factor B more so than factor A. Inhibiting
      activity of factor B is displayed at higher ascorbate concentrations than that of
      factor A. Increasing the ionic strength strongly stimulated the inhibitory
      capacity of factor A, but only slightly that of factor B. Differences were
      observed in pH-dependence, though both factors were more active in neutral media
      (pH 6.2-6.8). Factors A and B had different time-courses of inhibition of TBARS
      formation and suppression of chemiluminescence intensity. Factor B was more
      stable in the course of thermal treatment. Repeated freezing and thawing did not
      affect the activity of both factors. However, factor A could be inactivated by
      ultrasonic treatment, whereas factor B was unaffected. A function of these
      factors could be to create more favourable conditions for the interaction of
      ascorbate as a very hydrophilic molecule with membrane-bound hydrophobic
      radicals.

PMID- 7820883
TI  - Metabolic activation of the olfactory toxicant, dichlobenil, in rat olfactory
      microsomes: comparative studies with p-nitrophenol.
AB  - The tissue-specific toxicity of the herbicide, dichlobenil (2,6
      dichlorobenzonitrile), in the olfactory mucosa is related to a cytochrome P450
      (P450)-dependent metabolism, depletion of glutathione and covalent binding of
      metabolites. Pretreatment of mice with diethyldithiocarbamate (DEDTC) protected
      against the dichlobenil-induced necrosis. Addition of DEDTC abolished the
      covalent binding of [14C]-dichlobenil to rat olfactory microsomes, whereas
      P4502E1-substrates such as ethanol, acetone or p-nitrophenol (NP) had no effect.
      The NP-hydroxylation in olfactory microsomes was > 6 times higher than that in
      liver microsomes and was markedly decreased following addition of dichlobenil,
      DEDTC or metyrapone. In liver microsomes of acetone-treated rats the NP
      hydroxylation was markedly decreased following addition of DEDTC, whereas
      metyrapone and dichlobenil had no effect. In acetone-treated rats, the NP
      hydroxylation and the metabolic activation of [14C]-dichlobenil in olfactory
      microsomes were decreased to 50 and 73% of untreated controls, respectively,
      whereas in liver microsomes these activities increased > 6 and 3.5-fold,
      respectively. An antibody to P4502E1 had no effect on the NP-hydroxylation or
      metabolic activation of [14C]-dichlobenil in olfactory microsomes, whereas the NP
      hydroxylation in liver microsomes of acetone-treated rats was markedly decreased.
      In conclusion, the results do not support a major role for P4502E1 in the
      metabolic activation of dichlobenil or hydroxylation of NP in rat olfactory
      microsomes and suggest that these catalytic activities in the olfactory mucosa
      may represent a common form of P450.

PMID- 7820884
TI  - P450 enzyme CYP2B catalyzes the detoxification of diisopropyl fluorophosphate.
AB  - Phenobarbital and some other enzyme-inducers are known to reduce organophosphate
      toxicity. One suggested mechanism is the induction of liver cytochrome P450
      enzymes catalyzing monooxygenation reactions. The aim of the present study was to
      elucidate the cytochrome P450 subfamily, or P450 isoenzyme(s), participating in
      the detoxification of diisopropyl fluorophosphate (DFP) in the rat. DFP resulted
      in a type I spectrum in liver microsomes from phenobarbital- or RP 52028-treated
      rats (binding constants 0.32 and 0.17 microM, respectively) and in a purified
      P450 preparation enriched with CYP2B. The spectrum was reversible by metyrapone,
      an inhibitor of the CYP2B enzyme subfamily. The 7-pentoxyresorufin O-dealkylase
      activity was inhibited by DFP in liver microsomes from phenobarbital- or RP 52028
      treated rats and in a reconstituted system containing the purified CYP2B
      preparation. In microsomes from phenobarbital-pretreated rats, the inhibition was
      of a mixed type, i.e., competitive-non-competitive (Km = 0.5 microM; Ki = 6
      microM). The microsomal fractions of livers from phenobarbital- or RP 52028
      treated rats detoxified DFP effectively in vitro, as measured by a decrease in
      the DFP inhibition of cholinesterase activity. This detoxification was
      antagonized by metyrapone and by an antibody raised against purified CYP2B
      preparation. Clotrimazole, an inhibitor of P450 enzymes, inhibited the
      detoxification of DFP in rat liver in vivo. A genetically-modified hamster cell
      line expressing CYP2B1 oxidized NADPH in the presence of DFP. No such oxidation
      was detected in the parent cell line. These studies suggest that CYP2B1
      metabolizes DFP and may significantly contribute to the detoxification of this
      organophosphate in vivo.

PMID- 7820885
TI  - Mitomycin C-induced distortions of DNA at minor alkylation sites.
AB  - Reductively-activated mitomycin C (MC) presents a high specificity to the 5'-CG
      site and to a lesser extent the 5'-GG site. However, its affinity is different
      for each 5'-CG site. This was evidenced by using the 3'-5' exonuclease activity
      of T4 DNA polymerase on a short DNA fragment exposed to MC, which was gradually
      activated by several Na2S2O4 additions. The time-delayed appearance of some
      exonuclease digestion stop sites (corresponding to MC-monofunctional adducts)
      suggests that MC discriminates between very fine structural variations. The
      feature of the stop sites suggests a good fit of MC in the DNA groove, in the
      case of the major alkylation sites, but not in the case of a minor 5'-TG
      alkylation site. Furthermore, it is evidenced by the use of the chemical probe
      hydroxylamine (HA) that MC-monoalkylation of 5'-CG (or 5'-GG) does not induce
      notable local structural disturbance of the DNA double helix, as opposed to
      alkylation of the 5'-TG site of minor specificity, which leads to significant
      local DNA distortion. This suggests that the 'in vivo' effect of MC is related,
      not only to amount of alkylated sites (essentially 5'-CG sites), but also to
      possible local DNA deformations (at minor alkylation sites).

PMID- 7820886
TI  - Accumulation of metallothionein and its multiple forms by zinc, cadmium and
      dexamethasone in human peripheral T and B lymphocytes and monocytes.
AB  - Metallothionein (MT) is produced at high rates in isolated monocytes, and T and B
      lymphocytes during induction in vitro. At optimal concentrations, 125 microM for
      Zn and 10 microM for Cd and dexamethasone (dex), MT was demonstrated after only 2
      h in some cases, and in all cell types substantial levels were measured after 1
      day of exposure to all three inductors. With Cd, lower amounts of MT were found,
      but maximum levels were reached faster than with Zn. The same result was found
      for dex compared to Zn. Zn and dex in combination showed the same accumulation
      rate as Zn alone. If the inductors were used in lower concentrations than
      optimal, reduced accumulation rates occurred, particularly during the first part
      of the exposure period. No MT was found for concentrations below 5 microM Zn, 1
      microM Cd or 0.5 microM dex. The constitutive levels of MT (mean +/- S.E.M.) were
      0.11 +/- 0.05, 0.54 +/- 0.3, 0.06 +/- 0.05 and 0.15 +/- 0.08 nmol Cd bound/5 x
      10(6) unseparated mononuclear cells (MNC), monocytes, T lymphocytes and B
      lymphocytes, respectively. Monocytes accumulated 19 times and B lymphocytes 6
      times more MT than T lymphocytes after 2 days of exposure to 125 microM Zn.
      Despite these differences in accumulated amounts of MT, the fold accumulation
      values were rather similar between the cell types, reflecting corresponding
      variations in background MT levels. After exposure of unseparated MNC to 125
      microM Zn for 2 days, removal of the metal caused constitutive MT levels to be
      reestablished in 5 days. Five different MT forms, all capable of Cd complexation,
      were demonstrated in these cells. These forms had kinetically different behaviour
      during Zn exposure among the cell types, and the response to Cd was different
      from the Zn response. The results indicate metals to be closely controlled in MNC
      and emphasize a role for multiple MT forms in the process of regulation.

PMID- 7820888
TI  - Forensic entomology.

PMID- 7820887
TI  - Junctional sites of erythrocyte skeletal proteins are specific targets of tert
      butylhydroperoxide oxidative damage.
AB  - The oxidative denaturation of the erythrocyte membrane, which is considered a
      major cause of the haemolytic process, was evaluated upon 'in vitro' oxidative
      stress with tertbutylhydroperoxide. Biochemical and ultrastructural analyses were
      performed to point out the effect of this substance on the skeletal network,
      which is mainly responsible for red cell shape and viability. Moreover, cell
      morphology was observed by scanning electron microscopy and membrane rigidity
      assessed by EPR measurements. The most relevant features of the membrane
      denaturation were, (i) lipid peroxidation, as assessed by malonidialdehyde
      production, (ii) spectrin and ankyrin degradation with simultaneous globin
      binding to the membrane, as evidenced by electrophoretic pattern of red cell
      ghosts. These phenomena were related to the drug concentration in the incubation
      medium, and accompanied by depletion of intracellular reduced glutathione. The
      denaturation of protein components hindered the release of spectrin in a
      hypotonic extraction medium and could be only partially reversed by
      dithiothreitol. The extensive membrane protein and lipid degradation, at high
      drug concentration, was coherent with a marked increase of membrane order
      (membrane 'rigidity'). No clustering of intramembrane proteins was shown by the
      transmission electron microscopy images. At the same time scanning electron
      microscopy demonstrated shrinking and disco-stomatocytic deformation of
      erythrocytes. Ultrastructural analysis of the membrane skeleton by fluorescence
      labelling of spectrin and actin, allowed to point out that exposure to t-BHP
      caused the marginalization of spectrin and the rearrangement of actin molecules
      with formation of micro aggregates, so that a detachment of actin from the
      spectrin network was suggested. In addition to the generalized damage of red cell
      membrane, tertbutylhydroperoxide was found to induce a specific alteration of the
      skeletal network at the horizontal junction sites involving spectrin, actin, and
      protein 4.1 and thus to modify the cytoskeletal assembly. This effect on the
      membrane skeletal components was consistent with the hypothesis that oxidative
      stress plays a key role in the haemolytic process.

PMID- 7820889
TI  - Helicobacter pylori: after ten years, still an enigma.

PMID- 7820890
TI  - Necrotising lymphadenitis of Kikuchi and Fijimoto in Sri Lanka.
AB  - We present the clinicopathological features of 10 patients with Kikuchi's
      lymphadenitis. It is important to distinguish this unusual form of necrotising
      lymphadenitis, both clinically and histologically, from lymphoma and infective
      lymphadenitis, including mycobacterial infection. The 10 lymph node biopsies
      studied were from young adults (9 women) with fever, cervical lymphadenopathy and
      elevated ESR. This is the first documentation of this condition in Sri Lanka.
      This benign self-limiting condition can be mistaken for lymphoma or infective
      lymphadenitis.

PMID- 7820892
TI  - Econazole and clotrimazole in the treatment of vaginal candidiasis: a double
      blind comparative study.
AB  - OBJECTIVES: To compare the efficacy of treatment with econazole and clotrimazole
      in patients with vaginal candidiasis. DESIGN: A double blind study. Patients with
      vaginal candidiasis were randomly treated with vaginal depot preparations of
      econazole and clotrimazole. Efficacy after treatment by reduction of symptoms, a
      gynaecological examination and microbiological analysis of vaginal fluid. Adverse
      reactions were noted. SETTING: University gynaecological clinic at the de Soysa
      Hospital for Women, Colombo. PATIENTS: 102 patients microbiologically confirmed
      as having vaginal candidiasis. RESULTS: Two weeks after econazole treatment 19%
      still complained of a discharge and 7.5% had pruritus. The respective values for
      clotrimazole were 18% and 12%. The finding on gynaecological examination
      generally supported the reduction of symptoms. Microbiological assessment showed
      that 90.5% in the econazole group and 96% in the clotrimazole group became
      culture negative at two weeks after treatment. Adverse effects were similar in
      incidence and number for both treatment groups. Econazole was less acceptable to
      patients than clotrimazole. CONCLUSIONS: Econazole and clotrimazole are of equal
      efficacy for treatment of vaginal candidiasis. Econazole was less acceptable to
      patients.

PMID- 7820891
TI  - Early complications of packing after nasal surgery with three different
      materials.
AB  - OBJECTIVE: To investigate and compare the early complications of nasal packing
      with three different packing materials after surgical trimming of nasal
      turbinates. DESIGN: From a group of patients admitted to two Ear, Nose and Throat
      Departments for surgical trimming of inferior turbinates, those who consented
      were included in this study. Randomised patient packs were used and randomisation
      was carried out by a third party not directly involved in the study. Patients'
      nostrils were packed with calcium sodium alginate (Kaltostat), glove finger packs
      or trousered paraffin gauze. SETTING: Two District General Hospitals (DGH) in the
      United Kingdom (UK) during the period from February 1989 to June 1990. SUBJECTS:
      92 patients between the age of 16 years and 60 years who consented out of a
      population who were admitted to two DGHs for surgical trimming of inferior
      turbinates. MAIN OUTCOME MEASURES: The state of the nostrils in each patient was
      assessed by the authors (authors 1 and 3 in Hospital 1 and author 2 in Hospital
      2) at the time of discharge and at a postoperative outpatient visit at 3 weeks
      after discharge. RESULTS: 5% of nostrils packed with calcium sodium alginate
      (Kaltostat), 27% of nostrils packed with glove finger packs and 20% of nostrils
      packed with paraffin trouser packs were found to have clots on discharge from the
      hospital. At the post-discharge followup, when each complication was considered
      separately, there were more complications in the group who had their nostrils
      packed for 48 hours (14.2%) than in those who had packs in for 24 hours (7.3%).
      Significantly less complications were seen at 3 weeks with paraffin gauze packs
      (6.6%) than in the other two packing material (13.9%). CONCLUSIONS: Our findings
      suggest that, of the pack types studied 1) nostrils packed with calcium sodium
      alginate (Kaltostat) leave less clots in the nostrils 2) leaving packing in for
      48 hours produces significantly more complications in the early post-operative
      period especially with calcium sodium alginate.

PMID- 7820893
TI  - Hypokalaemic periodic paralysis in central Sri Lanka.
AB  - We describe 14 Sinhalese male patients with hypokalaemic periodic paralysis
      (HPP). The age at onset was between 10 and 32 years. Each paralytic episode
      lasted from 6 to 48 hours (except in one patient who had an attack lasting 5
      days). The frequency of attacks varied from 8 to 10 per month in one patient to
      only 2 attacks over a period of 16 years in another. Four patients (28.6%) had a
      family history of the disease. Hypokalaemia (serum potassium 1.5 to 3 mmol/l) was
      documented during an attack in 11 patients. No cause for hypokalaemia was evident
      in any of them. Investigations including EMG, thyroid hormone level and skeletal
      muscle histology were within normal limits between episodes. All the patients
      responded well to treatment with potassium supplementation, alone or with
      acetazolamide.

PMID- 7820894
TI  - The work of a diabetes clinic: an audit.
AB  - OBJECTIVE: To audit outcome and process of care at the diabetic and medical
      clinics. DESIGN: Prospective interventional study with each patient acting as a
      retrospective control. SETTING: The Sri Jayawardenepura General Hospital (SJGH)
      diabetic clinic. PATIENTS: 250 consecutive patients with NIDDM transferred to the
      diabetic clinic from the general medical clinic. INTERVENTION: Participation in a
      structured scheme of health care delivery which included patient education
      dietary advice and screening for complications. MEASUREMENTS: Fasting blood
      glucose, patients' knowledge score, patient satisfaction, frequency of screening.
      RESULTS: A Significant improvement was seen after attendance at the diabetic
      clinic in fasting blood glucose (8.7 SD 1.3 vs 12.5 SD 3.2 mmol/l, p < 0.05),
      body mass index (26.8 SD 0.6 vs 27.4 SD 0.4 kg/m2, p < 0.05), admission rates
      (10% vs 21%, p < 0.05), patients knowledge score (76 SD 12 vs 42 SD 16%, p <
      0.05) rates of screening for retinopathy (88% vs 6%, p < 0.05) and patient
      satisfaction in clinical care (87% vs 13%, p < 0.05). There was no significant
      improvement in cholesterol levels (5.7 SD 0.1 vs 5.8 SD 0.9 mmol/l). CONCLUSIONS:
      The diabetes clinic is a more efficient system and a more appropriate setting to
      care for patients with NIDDM.

PMID- 7820895
TI  - The use of chloroquine during pregnancy.

PMID- 7820896
TI  - Acalypha indica induced haemolysis in G6PD deficiency.

PMID- 7820897
TI  - Delta-bilirubin: an unrecognised entity.

PMID- 7820898
TI  - The MD or the MRCP? A dilemma for the Sri Lankan physician.

PMID- 7820899
TI  - Family medicine, a postgraduate discipline.

PMID- 7820900
TI  - Inhibitors of sterol synthesis. Synthesis and spectral properties of 3 beta
      hydroxy-5 alpha-cholestan-15-one and its 17 beta-epimer and their effects on 3
      hydroxy-3-methylglutaryl coenzyme A reductase activity.
AB  - 3 beta-Hydroxy-5 alpha-cholestan-15-one (2a) and its 14 beta-epimer 2b were
      prepared from 3 beta-acetoxy-5 alpha-cholest-8(14)-ene (3). Hydroboration of 3 at
      45-50 degrees C gave a mixture of 5 alpha,14 alpha-cholestane-3 beta,15 alpha
      diol and 5 alpha,14 beta-cholestane-3 beta,15 beta-diol, which were separated on
      silica gel as their 3 beta-tert-butyldimethylsilyl ethers 5a and 5b. Oxidation of
      5a with pyridinium chlorochromate, followed by desilylation with
      tetrabutylammonium fluoride gave 2a. Analogous transformations of 5b gave 2b
      contaminated with 2a. Desilylation of 5b followed by oxidation with pyridinium
      chlorochromate resulted in a mixture composed mainly of 5 alpha,14 beta
      cholestane-3,15-dione and 2b. Successive chromatographic separations on silica
      gel and reversed phase media gave 2b of high purity. Compound 2a was also
      prepared by lithium-ammonia reduction of 3 beta-hydroxy-5 alpha-cholest-8(14)-en
      15-one (96% yield) and by selective reduction of 5 alpha-cholestane-3,15-dione
      with lithium tri-tert-butoxyaluminum hydride (90% yield). Isomers 2a and 2b were
      readily epimerized under acidic or basic conditions or under conditions used for
      gas chromatographic analysis. The purities of 2a and 2b were measured from
      nuclear magnetic resonance (NMR) spectra; chromatographic methods gave less
      reliable estimates of purity. NMR data also showed that ring C of the 14 beta
      sterols is predominantly in a chair conformation. The effects of 2a and 2b on the
      levels of 3-hydroxy-3-methylglutaryl coenzyme A reductase have been studied in
      Chinese hamster ovary cells.

PMID- 7820901
TI  - Detection and characterization of the onset of bilayer packing defects by
      nanosecond-resolved intramolecular excimer fluorescence spectroscopy.
AB  - Bilayer packing defects in binary dilinoleoylphosphatidylethanolamine and 1
      palmitoyl-2-oleoylphosphatidylcholine (DLPE/POPC) lipid mixtures have been
      studied by the use of nanosecond-resolved intramolecular excimer fluorescence
      spectroscopy. Frequency-domain fluorescence intensity decays of dual-chain
      labelled dipyrenyl lipids of different chain lengths in DLPE/POPC mixtures were
      acquired at both the monomer (392 nm) and excimer (475 nm) emission channels and
      at 20 degrees C. On the basis of a new intramolecular excimer formation kinetic
      model, the extent of aggregation and the rotational mobility, in terms of the
      equilibrium constant of the monomer to aggregated state and the excimer
      association rate constant, respectively, of the intralipid pyrenes were
      calculated from the frequency-domain data. Within the range of 60-100% DLPE where
      bilayer defects are known to coexist with bilayer and non-bilayer states, a
      prominent peak in the equilibrium constant and a concomitant dip in the excimer
      association constant at approximately 80% DLPE were observed. Our nanosecond
      resolved fluorescence results suggest that the intramolecular excimer kinetic
      parameters of dipyrenyl lipids are very sensitive to the onset of bilayer packing
      defects in lipid membranes. Moreover, the onset of bilayer defect state is
      characterized by the greater extent of aggregation and more hindered rotational
      mobility of the acyl chains as compared with the bilayer (0% DLPE) and non
      bilayer inverted hexagonal (100% DLPE) states of the lipid membranes.

PMID- 7820902
TI  - Synthesis of heterocyclic platelet activating factor analogues.
AB  - The synthesis of heterocyclic analogues of the platelet activating factor is
      described. The preparation starts with acylating rac-tetrahydro-1,3-thiazine-4
      carboxylic acid ethyl ester, with palmitoyl chloride to form the amide linkage.
      Following ester reduction, the phosphocholine part is introduced via 2-chloro-2
      oxo-1,3,2-dioxaphospholane and subsequent ring opening with trimethylamine under
      pressure. Furthermore, the related L-thiazolidine analogue is prepared using the
      same procedure. In addition the sulfinyl and sulfonyl derivatives of this
      compound are obtained by oxidation with 3-chloro-perbencoic acid. From one
      sulfinyl intermediate the diastereomeres are separated and their conformations
      are determinated by 13C-NMR spectroscopy.

PMID- 7820903
TI  - The aggregation behaviour of two structurally isomeric glycolipids.
AB  - The two structurally isomeric glycolipids N-octyl-(1-hexadecylamido)-beta-D
      glucopyranoside (Glc-N-[8/16]) and N-hexadecyl-(1-octylamido)-beta-D
      glucopyranoside (Glc-N[16/8]) were synthesized. The lyotropic phase behaviour of
      these isomers was investigated in order to determine the extent to which the
      relative disposition of the alkyl chains with respect to the amide unit affects
      the aggregation properties of the amphiphiles. Both isomers exhibit lamellar and
      inverse topology cubic mesophases. The extent and polymorphism of the non
      lamellar phases appear to be more pronounced in the Glc-N-[8/16] isomer relative
      to the Glc-N-[16/8] isomer. A molecular mechanics study was undertaken in an
      attempt to rationalize this behaviour.

PMID- 7820904
TI  - Effects of farnesol on the thermotropic behavior of
      dimyristoylphosphatidylcholine.
AB  - Differential scanning calorimetry (DSC) and DPH fluorescence anisotropy have been
      used to investigate the effects of trans-trans farnesol on the physical
      properties of model membranes and extracted cell lipids. Farnesol was shown to
      have a significant effect on the gel to liquid-crystal phase transition
      temperature, the enthalpy of the transition and the transition co-operativity for
      extruded vesicles of dimyristoylphosphatidylcholine (DMPC). The phase transition
      of DMPC vesicles was eliminated at 25 mol% farnesol. Farnesol decreased the
      fluorescence anisotropy of the lipids extracted from human leukemia line CEM-C1
      cells.

PMID- 7820905
TI  - [Joubert syndrome].
AB  - Joubert's syndrome is clinically characterized by attacks of tachypnea
      alternating with respiratory pauses, abnormal ocular movements, psychomotor
      retardation, and ataxia. Anatomic anomalies include cerebellar vermis agenesis
      with dilatation of the fourth ventricle. It is an autosomal recessive disorder;
      onset is in the neonatal period and prognosis is severe.

PMID- 7820906
TI  - [Indications for and limitations of vaginal hysterectomy].

PMID- 7820908
TI  - Frequencies of unstable chromosome aberrations in peripheral blood lymphocytes of
      Chernobyl emergency accident workers.
AB  - On the basis of the investigation of unstable chromosome aberrations in
      peripheral blood lymphocytes of Chernobyl accident emergency workers, of
      residents of the contaminated areas, of patients with blood diseases and of
      donor's blood irradiated in vitro it is stated that presence of unstable
      chromosome aberrations such as dicentrics in lymphocytes of emergency workers and
      residents indicates that they have been overexposed. However, in the absence of
      the described aberrations in individuals involved in emergency work or in
      residents years after accident it is impossible to reject the overexposure.

PMID- 7820907
TI  - [Coexistence of 2 distinct populations of neutrophil granulocytes, one totally,
      the other partially deficient in myeloperoxidase].

PMID- 7820909
TI  - [Prion diseases].

PMID- 7820910
TI  - [Medicine, efficiency and economy in Greek thinking of classical times].

PMID- 7820911
TI  - [Severe neutropenia in infectious mononucleosis].

PMID- 7820912
TI  - Production and characterization of monoclonal antibodies directed against high
      and low molecular weight kininogens.
AB  - HMWK and LMWK were purified from human plasma by ion exchange and affinity
      chromatography and used to raise anti-kininogen monoclonal antibodies. The Ig
      class and affinity of these Mab's that are directed at the heavy chain of the
      kininogens, were determined. Plasma samples of two patients, one with acquired C1
      inhibitor deficiency and angioedema and one with idiopathic angioedema were
      analized by immunoblotting with these Mab's. Both were found to have cleaved HMWK
      during clinical attacks.

PMID- 7820914
TI  - Contact lens practice in the managed care environment.

PMID- 7820913
TI  - Lower incidence of contact lens related ulcers in Sweden: is patient education a
      key?

PMID- 7820915
TI  - Soft contact lenses and corneal astigmatism.

PMID- 7820916
TI  - The annualized incidence of contact lens induced keratitis in Sweden and its
      relation to lens type and wear schedule: results of a 3-month prospective study.
AB  - All cases of contact lens induced keratitis (epithelial defects with an
      underlying infiltrate or ulcer) among cosmetic wearers in Sweden were collected
      in a 3-month prospective study and analyzed for risk factors in relation to lens
      type and wear schedule. Every ophthalmologist in Sweden was invited to
      participate and 100% responded. Viral cases were excluded. The number of lens
      wearers in Sweden, subdivided by lens type and wear schedule, was obtained in a
      parallel 3-month study among 71% of the lens fitters, who counted all their
      wearers, recording lens type and wear schedule as well as revisit and replacement
      schedules. The annualized incidence per 10,000 wearers was 1.48 for daily wear of
      rigid gas permeable lenses, 2.16 for daily wear and 10.00 for extended wear of
      disposable soft lenses, and 2.17 for daily wear and 13.33 for extended wear of
      conventional soft lenses. Thus, extended wear was associated with a significantly
      (P < 0.01-0.001) higher (5-6 times) risk of keratitis than daily wear. There were
      no other significant differences between the incidence figures. The Swedish
      incidence figures were approximately half as high as those reported in the U.S.
      Of the lesions, only 12% were located within the pupillary area and only 8% were
      corneal ulcers. Only three patients (12%) suffered a decrease in visual acuity.
      Severe keratitis was significantly (P < 0.01) more common among conventional soft
      lens wearers (accounting for all ulcers, all lesions within the pupillary area,
      and all decreases in visual acuity) than among wearers of disposable lenses.

PMID- 7820917
TI  - Clinical evaluation of a computerized topography software method for fitting
      rigid gas permeable contact lenses.
AB  - Computerized videokeratoscope software programs now have the ability to assist in
      the design of rigid gas permeable (RGP) contact lenses and simulate fluorescein
      patterns. We evaluated the performance of Computed Anatomy's Topographic Modeling
      System (TMS-1) and its Contact Lens Fitting Program (version 1.41) in fitting RGP
      lenses in 31 subjects. Computerized topographic analysis, balanced manifest
      refraction, slit lamp examination, and keratometry were performed. Initial lens
      parameters were ordered according to manufacturer's programmed recommendations
      for base curve, power, lens diameter, optic zone diameter, and edge lift. Final
      lens parameters were based on clinical performance. Lenses were recorded for base
      curve changes of 0.1 mm or more, power alterations of +/- 0.50 D or more, or for
      any alteration in diameter/optic zone. Twenty-seven patients were analyzed for
      all five recommended parameters. Thirteen of 27 patients (48%) required no
      parameter changes. Nine of 27 patients (33%) required one parameter change, four
      of 27 patients (15%) required two parameter changes, and one patient (4%) needed
      three parameters altered. The most prevalent change was a power alteration,
      required in nine of 27 patients (33%); however, comparisons of all initial to
      final parameters showed no statistically significant differences. Comparison of
      initial base curves to that which would have been chosen via standard keratometry
      also showed no significant difference. This study found the TMS-1 default lens
      recommendations to be clinically unacceptable. This system, however, could be an
      alternative method of initial lens selection if used to titrate a fit or if
      software enhancements are incorporated to account for lens movement and flexure.

PMID- 7820918
TI  - Use of confocal microscopy to determine matrix and surface protein deposition
      profiles in hydrogel contact lenses.
AB  - We present a new method that combines protein-specific fluorescence staining with
      confocal microscopy to simultaneously measure matrix and surface protein deposits
      via optical sectioning of hydrogel contact lenses. Tetramethylrhodamine
      isothiocyanate (TRITC), Texas Red, fluorescein isothiocyanate (FITC), and
      fluorescein succinate were used to selectively react with the lysine residues of
      protein deposits for two lens types (etafilcon A [a 58% water, ionic lens] and
      polymacon [a 38% water, nonionic lens]). Because TRITC and Texas Red gave high
      levels of nonspecific staining, they were discontinued. Following exhaustive
      rinsing of lenses, central lens buttons were analyzed using a Bio-Rad MRC-500
      laser scanning confocal microscope. Optical sections were made every 4 microns at
      200x magnification, and the fluorescence signals were processed using image
      analysis software. The high water ionic material accumulated protein much more
      rapidly than the low water nonionic material. For a given lens type a correlation
      was observed between the wear time and the degree of protein deposition; however,
      we did observe significant inter-subject variations in total protein. From this
      preliminary work, we conclude that this confocal method is feasible and desirable
      for simultaneous determination of surface and matrix protein deposition.

PMID- 7820919
TI  - Lipid deposits on hydrophilic and rigid gas permeable contact lenses.
AB  - Never-worn hydrophilic contact lenses (from each of the four FDA-classified
      groups) and rigid gas permeable (RGP) lenses were individually incubated for 24
      hours at 37 degrees C with constant stirring in a mixture of 992 microL of 0.9%
      saline and 8 microL of a 1:1 chloroform:methanol solution of lipids (20 mg each
      of cholesterol, free fatty acid, triglyceride, fatty acid methyl ester, and
      cholesteryl ester, representative of lipids commonly found in the tear film). The
      lipid material deposited onto each lens was then extracted and its components
      separated using high performance thin layer chromatography. The chromatograms
      were analyzed by densitometry. Results indicate significant lipid deposition onto
      all lens types, with the siloxanyl alkyl acrylate RGP-type lenses accumulating
      two to three times as much total lipid as any of the other lenses. This suggests
      that hydrophobic RGP lenses, which also have lipophilic character, are most prone
      to develop lipid deposits. Among the hydrophilic lenses, nonionic polymer
      matrices and higher water content tended to increase lipid deposition.

PMID- 7820920
TI  - Disinfection efficacy in an integrated ultraviolet light contact lens care
      system.
AB  - We evaluated a new integrated contact lens care system that combines fluid
      turbulence for lens cleaning with ultraviolet (UV) light for solution
      sterilization. The ultraviolet light system was used to clean and disinfect 42
      soft contact lenses (water contents: 38.6%, 43%, 55%, and 70%) and two rigid gas
      permeable lenses. Test lenses were contaminated with 10(6) cells/mL of Bacillus
      pumilus, Aspergillus niger, Pseudomonas aeruginosa, and Acanthamoeba castellanii
      and subjected to a 15-minute cleaning-disinfection cycle. Bathing solutions and
      contact lenses were cultured at various time intervals and at the end of the
      cycle. All bathing solutions and all lenses but one were found to be sterile
      after one cycle. All units effectively disinfected solutions and contact lenses.
      This device may be an effective alternative to existing contact lens care
      systems.

PMID- 7820921
TI  - A measurable subjective patient response to the dry eye.
AB  - Patients with "dry eyes" are often poor prospects for successful contact lens
      wear. Screening out these patients could improve contact lens practice. Currently
      used diagnostic tests, such as the Schirmer strip test or the time for tear film
      breakup, are not very effective in identifying the dry eye patient who may have
      trouble wearing a contact lens. A new test is described here that asks the
      patient to report the time to disappearance of the pillar-like flare image seen
      above a disk light source. A flare image is created by the tear prism in the
      lower lid margin. This test, when it was applied to a small group composed of
      young, middle-aged, and elderly adults, was able to correlate rapid disappearance
      of the flare image with the presence of typical dry eye syndrome complaints in
      two subjects.

PMID- 7820922
TI  - Excimer laser phototherapeutic keratectomy for anterior corneal pathology.
AB  - The argon-fluoride 193 nm excimer laser is currently under investigation in the
      United States for both refractive and therapeutic indications. We report the
      results of phototherapeutic keratectomy (PTK) on 20 eyes of 19 patients. All
      patients had corneal pathology in the anterior one-third of the cornea. Mean
      follow-up was 7.8 months. While results are difficult to quantify because of
      varied indications, visual acuity improved in nine of 20 eyes (45%), remained
      unchanged in 10 eyes (50%), and worsened in one eye (5%). We judged 15 eyes (75%)
      to be functionally improved and one eye (5%) to be functionally worse. Our
      results demonstrate the effectiveness of excimer laser PTK for a wide variety of
      anterior corneal conditions. With continued improvement in patient selection and
      refinements in hardware, software, and surgical technique, PTK holds promise as
      an attractive alternative to more invasive and aggressive surgery.

PMID- 7820923
TI  - The long-term use of the SoftPerm lens on pellucid marginal corneal degeneration.
AB  - Pellucid marginal corneal degeneration (PMCD) is a corneal degeneration often
      confused with keratoconus because of the presence of high regular and irregular
      astigmatism. Vision correction can be achieved with rigid contact lenses, but the
      asymmetric topographic profile often makes obtaining a stable lens fit difficult.
      This study describes the fitting and satisfactory daily wear during 4 years of a
      combination lens design (2 years Saturn II and 2 years SoftPerm) on a patient
      with PMCD. The lens consisted of a central rigid gas permeable portion surrounded
      by a soft hydrophilic "skirt." Although the degree of astigmatism was high, 1.6
      mm (8.00 D) by keratometry and 12.00 D by refraction, the patient was able to
      wear the lens comfortably 12 hours per day and achieve visual acuity of 20/20.
      Routine keratometry, pachymetry, and slit lamp examination showed no significant
      corneal changes resulting from lens wear.

PMID- 7820924
TI  - Topographic evaluation of toric soft contact lens correction.
AB  - The anterior surface of the eye provides the greatest refracting surface to the
      optical system of the eye because of the large difference in refractive index
      between air and tissue. When a contact lens is placed on the eye, its anterior
      surface becomes the greatest refracting surface. Toric soft contact lenses have
      been designed to neutralize ocular astigmatism. We observed that topographic
      analysis of toric soft contact lenses on an astigmatic eye demonstrated residual
      astigmatism on the anterior surface of soft toric contact lenses. In this paper
      we show toric soft contact lens surface astigmatism by videokeratoscopy and
      interpret the origins of the astigmatism.

PMID- 7820925
TI  - Adults with Williams-Beuren syndrome: evaluation of the medical, psychological
      and behavioral aspects.
AB  - In order to evaluate the medical, psychological and behavioral aspects of
      Williams-Beuren syndrome in adulthood, data were collected on 11 patients aged 17
      to 66 years. The medical data did not confirm previous reports of significant
      morbidity. All adults were found to have a moderate or severe degree of mental
      handicap. They showed the same psychological profile as found in children: good
      verbal abilities, poor motor abilities, problems with sequencing and with
      performance tasks. The adults we evaluated showed little disturbing behavior in
      comparison to other mentally retarded subjects. They achieved a good level of
      autonomy. The majority lived at home with one or both parents and attended a day
      centre.

PMID- 7820926
TI  - Clinical features and natural history of Beckwith-Wiedemann syndrome:
      presentation of 74 new cases.
AB  - Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth syndrome with
      variable expression. To define the range and frequency of complications in BWS,
      we have studied a cohort of 76 affected patients (two previously reported). The
      most frequent complications were macroglossia (97%), abdominal wall defect (80%)
      and birth weight or postnatal growth > 90th centile (88%). Other common features
      were ear creases/pits (76%), facial naevus flammeus (62%), nephromegaly (59%) and
      hypoglycaemia (63%). Rarer complications included hemihypertrophy (24%),
      moderate/severe developmental delay (4%), congenital heart defects (6.5%),
      polydactyly (4%), neoplasia (4%) and cleft palate (2.5%). Pre-term labour
      occurred in 53% and polyhydramnios in 33% of BWS pregnancies. The six deaths all
      occurred in babies born pre-term, three of whom had major congenital
      abnormalities. Five patients (6.5%) from four kindreds had an unequivocal family
      history of BWS, but 15 of 68 apparently sporadic cases had a relative with
      possible BWS (minor features only). Incomplete penetrance may lead to familial
      BWS being underdiagnosed.

PMID- 7820927
TI  - Predictive testing for Huntington disease: social characteristics and knowledge
      of applicants, attitudes to the test procedure and decisions made after testing.
AB  - An investigation has been made of the social characteristics and knowledge and
      experience of Huntington disease (HD) for the first 80 individuals considering
      presymptomatic testing (applicants) at the medical genetics centres in Edinburgh
      and Glasgow and of attitudes to the test procedure and decisions made after
      testing for those who received a result. Sixty-one percent of applicants were
      female and 31% were over 40 years old. Almost all had a symptomatic parent but
      38% did not know HD was in their family until they were over 25 years old and 48%
      had never received genetic counselling. Thirty-eight percent of applicants first
      heard of the test at the genetic clinic, 20% from a relative and 20% from the
      media, but none had received information from their GP. Thirty-one applicants did
      not have the test because they voluntarily withdrew (17 individuals), their
      family structure was unsuitable or no informative result was possible (11
      individuals), or they were diagnosed clinically as being affected (3
      individuals). Those who voluntarily withdrew did not differ significantly from
      the 49 who received a result in social characteristics or knowledge and
      experience of HD. Twenty-two individuals were found to be at increased risk (IR)
      (> 50% of becoming affected) and 27 to be at decreased risk (DR) (< 50% of
      becoming affected). There was a median period of 9 months between entering the
      test procedure and receiving a result and the main criticism of the procedure was
      that it took too long to complete and several individuals experienced
      considerable anxiety while awaiting their result.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7820928
TI  - Sister chromatid exchange in families with Angelman or Prader-Willi syndrome.
AB  - Using estimation of numbers of sister chromatid exchanges arising in 15q11q13 as
      a measure, comparisons of the stability of the Prader-Willi syndrome critical
      region have been made. The groups studied included probands with Prader-Willi or
      Angelman syndromes either with or without a cytogenetically visible deletion in
      15q11q13, their parents, specifically those parents who had passed on the
      homologue which had become deleted, and a control group. No significant
      differences were found between any of the four groups, indicating that there was
      no increase in the instability of the PWSCR region as measured by sister
      chromatid exchange.

PMID- 7820929
TI  - Interstitial deletion of 22q11 in DiGeorge syndrome detected by high resolution
      and molecular analysis.
AB  - Two patients with DiGeorge syndrome (DGS), one with and one without
      characteristic dysmorphic facial features, were studied by high resolution
      banding, fluorescence in situ hybridization (FISH) and quantitative Southern
      blotting. In both patients, even in the one with no typical facial stigmata, a
      microdeletion within 22q11.2 was detected. FISH analysis, in particular, is most
      useful in screening for 22q11.2 segmental monosomy in patients with DGS and DGS
      related features.

PMID- 7820930
TI  - Osteoarthropathia psoriatica of one leg: a manifestation of somatic mosaicism?
AB  - A psoriatic osteoarthropathy localized in the left quadrant of a male patient is
      described. Diagnosis was made on the basis of bone scintigraphy (specific
      distribution pattern) and histological evaluation of a bone biopsy. There is no
      indication of psoriasis in the patient's family. Nor is there an association to
      psoriasis-typical HLA markers. Psoriasis of the skin has not been found.
      Environmental factors, including a Kobner phenomenon on the skeleton resulting
      from a trauma 13 years ago (hallux rigidus operation), are discussed in
      connection with this manifestation. The genetic aspects of this unusual
      localization are considered.

PMID- 7820931
TI  - The influence of genetic counselling in the era of DNA testing on knowledge,
      reproductive intentions and psychological wellbeing.
AB  - Subjects of reproductive age at risk of having an affected child with a severe
      single gene disorder such as Duchenne muscular dystrophy (DMD) or cystic fibrosis
      (CF) were surveyed to ascertain: their views on genetic counselling and antenatal
      testing; their knowledge of their risk of having an affected child; and their
      psychological wellbeing. Questionnaires were posted to 209 individuals at 130
      addresses; a 65% response rate was achieved. The majority of those surveyed were
      under 40 years of age (91%), half of them had received genetic counselling only
      once and for 47% the first encounter was after the diagnosis of their affected
      child. Most patients expressed their intention to use prenatal testing. However,
      less than 50% of those counselled knew their risk of having an affected child.
      Knowledge of risk was associated with the type of disease in the family (p <
      0.001) (inheritance of DMD was poorly understood by relevant subjects) and was
      positively associated with the participant's level of education (p < 0.05). We
      did not detect a significant association between the number of intended children
      and the risk of having an affected child. In terms of family relations, genetic
      counselling appears to be beneficial for the nuclear family, the couple and their
      children, but some counselees reported a deterioration in relations with other
      relatives. The results indicate that couples at risk of having a child with a
      severe genetic disorder value the counselling provided, but many of them do not
      remember important facts in relation to their risk status.

PMID- 7820932
TI  - Diphallus and associated anomalies with balanced autosomal chromosomal
      translocation.
AB  - We report a sporadic case of complete diphallus with multiple other anomalies in
      a premature newborn. Chromosomal analysis at the 500 band level showed an
      apparently balanced reciprocal translocation 46,XY, t(1;14)(p36.3;q24.3). The
      mother has a normal karyotype, but the father was not available for chromosomal
      analysis. The significance of this balanced chromosomal rearrangement and the
      possibility that the chromosomal breakpoints contribute to deregulation of
      mesodermal development is discussed.

PMID- 7820933
TI  - A Bgl I polymorphism in the human elastin gene (ELN).

PMID- 7820934
TI  - An alanine29-serine variant in exon 2 of the low density lipoprotein receptor
      gene: no association with hypercholesterolemia.

PMID- 7820935
TI  - DNA polymorphisms at the locus for human cholesteryl ester transfer protein
      (CETP) are associated with macro- and microangiopathy in non-insulin-dependent
      diabetes mellitus.
AB  - The effect of variation at the cholesteryl ester transfer protein (CETP) gene
      locus and in the apolipoprotein (apo) AI-CIII-AIV gene cluster on the
      susceptibility of individuals with non-insulin-dependent diabetes mellitus
      (NIDDM) to atherosclerotic vascular disease was studied in 136 male and 122
      female patients with NIDDM. The prevalence of myocardial infarction was high
      (38%) in patients with the EcoNI genotype 2-2 of the CETP gene locus (= 2-2;
      subjects homozygous for the absence of the restriction site) compared with
      patients with the genotype 1-1 (= 1-1; subjects homozygous for the presence of
      the restriction site) (18%, p < 0.02). The prevalence of any evidence of coronary
      heart disease (CHD) (presence of ischaemic ECG changes or definite myocardial
      infarction) was high in 2-2 (73%) compared with the genotype 1-2 (= 1-2;
      heterozygous for the presence of the restriction site) (52%, p < 0.02) and
      genotype 1-1 (p = 0.06). CHD was more prevalent in men with 2-2 (70%) than in
      those with 1-1 (42%, p < 0.05), but in women no significant differences were
      found in the prevalences of CHD between the EcoNI genotypes. Neuropathy was more
      often present in the patients with 2-2 (31%) than in those with 1-1 (12%, p <
      0.02) or 1-2 (14%, p < 0.01). Plasma total cholesterol and total- and VLDL
      triglycerides were higher in women with the EcoNI genotype 1-1 than in those with
      the genotype 1-2. In men no significant differences in plasma lipids were found.
      In addition, the prevalence of cerebrovascular disease was high (21%) in the
      patients with the genotype 1-1 of the TaqIB polymorphism compared with the
      genotype 2-2 (6%, p < 0.02). None of the alleles defined by four polymorphisms in
      the apo AI-CIII-AIV gene region were associated with an increased risk for
      macroangiopathy. The PstI polymorphism had an effect on plasma triglyceride
      levels. At the CETP locus one pair of loci (TaqIB and EcoNI) and three pairs of
      loci at the apo AI-CIII-AIV gene cluster (SacI and MspI, SacI and PvuII and MspI
      and PvuII) showed significant allelic association. In conclusion, the variation
      of CETP locus modulates the risk for diabetic complications in patients with
      NIDDM and the effect seems to be different between men and women. In contrast,
      the AI-CIII-AIV gene cluster polymorphisms seem not to be related to the risk of
      CHD in NIDDM.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7820936
TI  - Linkage between severe atopy and chromosome 11q13 in Japanese families.
AB  - Atopy, characterised by allergic asthma and rhinitis, is due to increased IgE
      responses to common aeroallergens. An Oxford group has described maternal
      inheritance of atopy, where there is significant linkage between IgE
      responsiveness and a VNTR marker D11S97 and a CA microsatellite within a
      candidate gene, the high affinity IgE receptor beta subunit (Fc epsilon RI beta),
      on chromosome 11q. Attempts at independent replication have produced conflicting
      results. We therefore recruited 270 atopic asthmatic probands in a Japanese
      community population for genetic linkage analysis. Four families, each with more
      than 15 meioses and a clear phenotype for atopy, were selected for genetic
      analysis. Atopy was defined as presence of all of raised total IgE, positive RAST
      and skin tests to three or more aeroallergens; non-atopy, as absence of all these
      criteria. Linkage analysis showed a maximum two-point lod score of 9.35 for
      D11S97 and Fc epsilon RI beta under the assumption of unequal rates of maternal
      and paternal recombination. Two families showed close genetic linkage with Fc
      epsilon RI beta with a pattern of maternal inheritance. These results from a
      Japanese population provide further evidence for genetic linkage between severe
      atopy and chromosome 11q13 and the likelihood of genomic imprinting at the locus.

PMID- 7820937
TI  - Inv dup(15): contribution to the clinical definition of phenotype.
AB  - One of the primary goals in medical genetics is a precise clinical definition of
      chromosomal diseases. This is now possible because of the increased number of
      case reports and new techniques. A male patient, without a clear-cut syndrome,
      was cytogenetically investigated. Chromosomal analysis showed a small
      unidentified bisatellited supernumerary marker. In situ hybridization with a
      biotin-labeled DNA probe for the chromosome 15 centromere (D15Z1) demonstrated
      that the marker was derived from chromosome 15. Hybridization with the Prader
      Willi Syndrome Cosmid biotinylated probe (localized to band 15q11-q13) showed a
      signal on both ends suggesting a marker with a symmetrical inv dup(15) and a
      breakpoint localized in q13. It was then possible to define the karyotype as:
      47,XY,+ inv dup(15) (pter-q13::q13-pter). All cases of inv dup(15) reported in
      the literature were reviewed, paying particular attention to the different
      breakpoints involved, in order to provide a better clinical definition of this
      syndrome.

PMID- 7820938
TI  - A 12-year preventive program for beta-thalassemia in Northern Sardinia.
AB  - From 1980 to 1991, 6.3% of the adult population of the province of Sassari,
      Northern Sardinia, underwent voluntary beta-thalassemia screening. Of the 28,000
      subjects examined, 15.7% proved to be heterozygotes for beta-thalassemia. In
      addition, the screening of 7500 students in 26 villages in Sassari province fixed
      the frequency of beta-thalassemia in this part of Sardinia at 10.4%. Of the 539
      couples at risk to be expected from this figure, the screening detected 43%
      (234). The data suggest that inductive screening played a major role in the
      efficiency of this preventive beta-thalassemia program. Follow up of 221
      pregnancies found to be at risk for homozygous beta-thalassemia and referred to
      the Antenatal Diagnosis Service, Cagliari, Southern Sardinia, showed that
      antenatal diagnosis was carried out in 80% of them. The overall percentage of
      couples refusing antenatal diagnosis was 10.8%, but over the years the acceptance
      rate for the procedure increased from 87% to 96%. Atypical hematological findings
      in 1.5% of 468 members of the couples at risk required globin chain synthesis and
      molecular analyses to define the precise beta-thalassemia genotype. Heterogeneous
      "mild" beta-thalassemia mutations as well as coexisting delta-thalassemia were
      found in silent type I and type II beta-thalassemia carriers which, without chain
      synthesis and DNA investigations, would have escaped detection.

PMID- 7820939
TI  - DNA polymorphisms of human apolipoprotein A-IV gene: frequency and effects on
      lipid, lipoprotein and apolipoprotein levels in a French population.
AB  - Genetic polymorphisms of apolipoprotein (apo) A-IV have been shown to influence
      lipoprotein metabolism in some human populations. In this study, we have
      evaluated the physiological effect of three apo A-IV polymorphisms (Gln360- >
      His, Thr347- > Ser and XbaI within the second intron of the apo A-IV gene), in a
      French population, on seven quantitative traits: total cholesterol and
      triglycerides, cholesterol of HDL, apo A-IV, apo B, apo A-I and glucose. The
      polymorphism at amino-acid 360 was determined by direct analysis of polymerase
      chain reaction products. The allele frequencies were 0.92 for the A-IV1 and 0.08
      for the A-IV2 allele. The genetic polymorphism at codon 347 was investigated by
      allele-specific oligonucleotide hybridization. The allele frequencies of the two
      alleles, A-IV347Thr and A-IV347Ser, were 0.78 and 0.22, respectively. The XbaI
      polymorphism was investigated by polymerase chain reaction followed by XbaI
      restriction enzyme digestion of the amplified products. The frequencies of the
      two apo A-IV alleles, XbaI-1 and XbaI-2, were 0.79 and 0.21, respectively. None
      of the three apo A-IV polymorphisms had a significant effect on lipoprotein,
      apolipoprotein and glucose levels.

PMID- 7820940
TI  - Possible localization of a major gene for cleft lip and palate to 4q.

PMID- 7820941
TI  - Exclusion of linkage to 14q23-24 in a family with Holt-Oram syndrome.
AB  - Holt-Oram syndrome is an autosomal dominant disorder with congenital heart
      defects and skeletal malformations of the upper extremities. A patient with a
      deletion of 14q23-24 and Holt-Oram syndrome has been described. In this report,
      however, genetic linkage to the 14q23-24 region is excluded in a multigeneration
      family with five available individuals affected with Holt-Oram syndrome. Familial
      Holt-Oram syndrome might be different from the syndrome with the 14q23-24
      deletion.

PMID- 7820942
TI  - Unilateral renal aplasia in X-linked Kallmann's syndrome.
AB  - Unilateral renal agenesis is an uncommon association with Kallmann's syndrome
      (KS) (hypogonadotrophic hypogonadism and olfactory defect). We have investigated
      affected individuals from six pedigrees: five with X-linked KS, and one with X
      linked KS and X-linked ichthyosis (XLI). Seventeen affected individuals have had
      renal imaging performed, and six scans demonstrated only one kidney. In addition,
      two pedigrees had males who died in the neonatal period with bilateral renal
      agenesis. Only two of the four affected individuals in the family with X-linked
      KS and X-linked ichthyosis (Pedigree 6) showed unilateral renal agenesis, despite
      all four patients demonstrating an interstitial deletion within the short arm of
      the X-chromosome. These data indicate that unilateral renal agenesis is much
      commoner than previously suspected in patients with X-linked Kallmann's syndrome,
      but that it may have incomplete penetrance within a family.

PMID- 7820943
TI  - Determination of haemophilia A carrier status from hair samples using polymerase
      chain reaction technique.
AB  - The usefulness of intragenic restriction fragment length polymorphisms (RFLPs)
      for BclI, HindIII and XbaI, adapted for polymerase chain reaction (PCR), was
      tested for the detection of haemophilia A carrier status in the consultant of a
      family in which only haematological information was available on the inheritance
      of the trait. Hair follicles were used as the non-invasive source of DNA. The
      mother was found to be homozygous for BclI and heterozygous for HindIII sites,
      whereas her status as regards informativeness could not be established for XbaI.
      On the basis of HindIII RFLP, the daughter was found to be a carrier of the
      haemophilia trait. This was confirmed by sequencing the amplified intron 19 of
      the mother and the daughter. The RFLP for XbaI did not appear to be suitable for
      carrier detection using PCR due to the difficulty of establishing homozygosity or
      heterozygosity from the results of digestion of the amplified product.

PMID- 7820944
TI  - Congenital cardiac defect in a patient with mosaic 45,X/46,XX,i(21q) karyotype.
AB  - A baby is described with 45,X/46,XX,i(21q) mosaicism. DNA analysis indicated that
      the abnormality arose from two independent postzygotic mutations in a 46,XX
      zygote, involving the paternal chromosomes 21 and X. In agreement with previous
      reports, most of the clinical dysmorphisms observed were consistent with Down
      syndrome. Moreover, congenital heart disease consisted of an atrioventricular
      canal associated with slight hypoplasia of the left ventricle and a mitral
      anulus, a complex defect including features found in both Down and Turner
      syndromes.

PMID- 7820945
TI  - A case of de novo interstitial deletion of chromosome 9(p12p13).
AB  - The present paper describes a girl with a small de novo deletion of chromosome
      9(p12p13). This deletion has not been published previously. The deleted fragment
      is clearly outside the region involved in the so-called deletion 9p syndrome. The
      patient had mild dysmorphic features and feeding problems during the first weeks
      of life, but is now developing well. Because of the lack of severe clinical
      features in this patient, we speculate that the deletion may be prevalent in
      other patients who have no clinical indication for chromosome investigation.

PMID- 7820946
TI  - Cholesteryl ester transfer protein: its role in plasma lipid transport.
AB  - 1. The cholesteryl ester transfer protein (CETP) is a hydrophobic glycoprotein
      which acts in plasma to redistribute cholesteryl esters and triglyceride between
      plasma lipoproteins. 2. CETP also plays an important role in determining the
      composition and particle size distribution of high density lipoproteins (HDL). 3.
      Activity of CETP may be regulated in four ways: By factors which influence the
      concentration of CETP in plasma; by the activity of CETP inhibitor proteins; by
      variations in the concentrations and compositions of donor and acceptor
      lipoproteins and by factors which influence the interaction of CETP with plasma
      lipoproteins. 4. The mechanism of action of CETP is uncertain. Two models have
      been proposed: (i) a shuttle model in which CETP physically transports lipids
      between lipoprotein particles and (ii) a ternary complex model in which CETP
      forms a bridge between two lipoprotein particles, enabling them to exchange
      lipids. 5. Evidence is accumulating that CETP may be a pro-atherogenic factor.

PMID- 7820947
TI  - Advantages of permutation (randomization) tests in clinical and experimental
      pharmacology and physiology.
AB  - 1. The statistical procedures that are used most commonly in clinical and
      experimental pharmacology and physiology are designed to test for differences
      between two means. 2. The classical procedures for detecting such differences are
      those in which, under the population model of inference, the test statistic is
      referred to the t- or F-distributions. The validity of statistical inferences
      from these tests depends on a number of assumptions. Foremost among these is that
      the experimental groups have been constructed by taking random samples from
      defined populations. The statistical inferences then apply to the sampled
      populations. 3. In biomedical research this sampling process is seldom followed.
      Instead, samples are usually acquired by non-random selection, and are then
      divided by randomization into experimental groups. This being the case, it is
      theoretically invalid to use the classical t- or F-tests to analyse the
      experimental results. 4. The validity of inferences from the classical tests also
      depends on other assumptions, such as that the sampled populations are normal in
      form and of equal variance. It is difficult to be certain that these assumptions
      are fulfilled when group sizes are small, as they usually are in pharmacology and
      physiology. Breach of them, especially if the groups are unequal in size, can
      lead to serious statistical errors. 5. Exact permutation tests are designed to
      make statistical inferences under the randomization model. These conclusions
      apply only to the results of experiments actually performed. By permuting the
      statistic of interest, such as the difference between arithmetic means, geometric
      means, medians, mid-ranges or mean-ranks of randomized groups of observations,
      the probability is calculated that the observed difference or a more extreme one
      could have occurred by chance. This inferential process is consistent with the
      way most biomedical experiments are designed and conducted. 6. Exact permutation
      tests, or sampled permutation tests based on Monte Carlo random sampling of all
      possible permutations, can now be performed on personal computers. They are
      commended to biomedical investigators as being superior to the classical tests
      for analysing their experimental results when the central tendencies of two
      independent groups, or of two sets of measurements on the same group, are
      compared. 7. When there is doubt that the assumptions for t-tests are satisfied,
      investigators sometimes use non-parametric rank-order procedures such as the
      Wilcoxon-Mann-Whitney rank-sum test for independent groups or the Wilcoxon signed
      rank-sum test for paired observations.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7820948
TI  - Clearance of chylomicron-like lipid emulsions is increased in normal rabbits but
      not in heterozygous Watanabe heritable hyperlipidaemic rabbits following
      treatment with cholestyramine or pravastatin.
AB  - 1. Cholestyramine and pravastatin are two potent hypocholesterolaemic drugs which
      lower plasma cholesterol by increasing the clearance of low density lipoproteins
      by high affinity uptake mechanisms. 2. We gave heterozygous Watanabe heritable
      hyperlipidaemic rabbits (hz-WHHL) cholestyramine and/or pravastatin for a two
      week period to try and ameliorate slow clearance of chylomicron remnants, which
      occurs because of reduced expression of the apolipoprotein B100/E receptor. 3. In
      hz-WHHL rabbits the clearance of chylomicron-like lipid emulsions, traced by the
      decrease in plasma cholesteryl oleate radioactivity was not improved following
      treatment with either of the cholesterol lowering drugs. 4. In contrast, control
      rabbits had significantly less chylomicron-like emulsion cholesteryl-ester
      radioactivity remaining at each time of blood sampling. 5. Similarly, the
      clearance of chylomicron-like emulsion triolein was enhanced in normal rabbits
      receiving cholestyramine or pravastatin, whereas there was no detectable increase
      in clearance in hz-WHHL rabbits. 6. Combined treatment with cholestyramine and
      pravastatin increased the rate of receptor-mediated uptake in vivo in control
      rabbits but not in hz-WHHL rabbits. 7. The plasma lipid profiles of control and
      hz-WHHL rabbits paralleled the patterns of chylomicron-like emulsion clearance.
      Moderate hypertriglyceridaemia was identified in hz-WHHL rabbits compared to
      controls and there was no change in plasma triglyceride or cholesterol following
      drug therapy. In contrast, control rabbits had decreased plasma lipids following
      cholestyramine or pravastatin treatment. 8. It appears that therapy with lipid
      lowering drugs increased chylomicron remnant clearance in control rabbits by up
      regulation of the apolipoprotein B100/E receptor.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7820949
TI  - Evidence for impaired endothelium dependent vasodilation in experimental left
      ventricular dysfunction.
AB  - 1. The full range of vascular reactivity was investigated in the hindlimb
      circulation of conscious, autonomically blocked rabbits with experimental
      (adriamycin-induced) cardiomyopathy. 2. Adriamycin treatment caused a significant
      reduction in left ventricular systolic function, as assessed by echocardiography
      (left ventricular fractional shortening, controls vs adriamycin treatment; 36.7
      +/- 1.7% vs 27.3 +/- 2.6%, P < 0.05). 3. Under pharmacological autonomic effector
      block, the range of the vasodilator response (resistance range, from resting to
      full vasodilatation) to acetylcholine was reduced by 41% (P < 0.05) and by 37%
      for adenosine (P < 0.05). Despite these changes the sensitivity (ED50) of the
      responses were unaltered. 4. The ED50 of constrictor responses to noradrenaline
      and angiotensin II were similarly unaltered, in conjunction with a non
      significant attenuation of the constrictor-response range. 5. These results
      suggest that in this model of experimental left ventricular dysfunction, the
      capacity of the hindlimb circulation to respond to regionally infused endothelium
      dependent vasodilators is attenuated.

PMID- 7820950
TI  - Disease-induced changes in alpha-adrenoceptor-mediated cardiac and vascular
      responses in rats.
AB  - 1. The physiological relevance of cardiac and vascular alpha-adrenoceptors may
      increase in disease states in which beta-adrenoceptors are altered. To test this,
      positive inotropic and vasoconstrictor responses to phenylephrine were measured
      in isolated tissues from rats with experimentally-induced hyperthyroidism,
      hypothyroidism and diabetes as well as in genetically spontaneous hypertensive
      rats (SHR). 2. In left atria, positive inotropic responses to phenylephrine were
      increased in hypothyroid and diabetic rats and abolished in hyperthyroid and SHR.
      3. In contrast, phenylephrine produced increased positive inotropy in left
      ventricular papillary muscles from hyperthyroid rats, increased potency in
      diabetic rats and negative inotropic responses in hypothyroid rats. 4. The
      potency of phenylephrine as a vasoconstrictor in thoracic aortic rings was
      increased in hyperthyroid and SHR and decreased in hypothyroid rats. 5. Thus,
      disease states which alter beta-adrenoceptor responsiveness can independently
      regulate atrial, ventricular and vascular responses to the alpha 1-adrenoceptor
      agonist, phenylephrine. Therefore, these disease states may alter the
      physiological control of the cardiovascular system by noradrenaline and
      adrenaline as well as the responsiveness in disease states to therapeutic agents
      acting via alpha-adrenoceptors.

PMID- 7820951
TI  - No effect of kinins on DNA synthesis in LNCaP prostate cancer cells.
AB  - 1. Prostate has kininogenase activity and expresses members of the tissue
      kallikrein gene family. The present study examined the effect of exogenous and
      endogenous kinins on growth of LNCaP prostate adenocarcinoma cells. 2. Rate of
      DNA synthesis was measured by incorporation over 4 h of [3H]-thymidine into a TCA
      insoluble fraction of LNCaP cells that had been cultured for 24 h. 3. Increased
      [3H]-thymidine incorporation was seen in response to 10 nmol/L testosterone (+103
      +/- 5 s.e.%), dihydrotestosterone (+113 +/- 14%) and R1881 (+64 +/- 10%) (P < or
      = 0.001; n = 4). 4. In contrast 0.05, 5 and 1000 nmol/L lysyl-bradykinin had no
      effect (15 +/- 4, 10 +/- 9 and 5 +/- 3 s.e.%, respectively; n = 7). Des
      Arg9[Leu8]-bradykinin (a B1 receptor antagonist) and/or D-Arg-[Hyp3,Thi5,8,D
      Phe7]-bradykinin (a B2 receptor antagonist), 1 nmol/L, and indomethacin, 5
      mumol/L, also had little or no effect. 5. In conclusion, kallidin and endogenous
      kinins and prostaglandins have little or no effect on DNA synthesis and therefore
      on the growth of LNCaP cells in comparison to the two-fold stimulation produced
      by androgens.

PMID- 7820953
TI  - Growth and metastasis of human breast cancers in athymic nude mice.
AB  - To evaluate critically the merit of utilizing a wound model for growing human
      tumors, a series of increasingly difficult human tumor types were tested for
      growth at sites of trauma in athymic nude mice. In vitro tumor lines as well as
      fresh tumors from the breast, colon, rectum, lung, and a metastasis from an
      unknown primary were intraperitoneally injected into mice subjected to intra
      abdominal organ injury. Successful xenografts were obtained from nine of 10 cell
      lines and 14 of 24 fresh tumors. The latter included five of six (83%) colon
      cancers, one lung tumor, metastatic tumor of unknown primary, three of four (75%)
      metastatic breast cancers and four of six (67%) estrogen receptor (ER)-negative
      breast primary tumors. Six ER-positive breast tumors tested failed to grow in
      mice without estrogen supplementation. Xenografts from two breast, two colon and
      the lung cancers formed spontaneous metastases and all xenografts tested were
      able to yield serial transplants in the surgical wound model. Histologically, all
      xenografts and their metastases were identical to their respective donor tumors.
      Transplantability in mice without exogenous estrogen supplementation was linked
      to the absence of estrogen and progesterone receptors in breast tumors.
      Transplantability of the cell lines was associated with the expression of cell
      surface receptors for fibronectin and hyaluronic acid. Receptors for other
      extracellular matrix components, namely, laminin, vitronectin, collagen,
      fibrinogen or von Willebrand factor were not associated with transplantability.
      These results demonstrate that a large proportion of human tumors, including the
      breast tumors, can be successfully xenografted into athymic mice by providing
      them with a healing wound environment, and that such xenografts grown at ectopic
      sites exhibit metastatic ability.

PMID- 7820952
TI  - Sublethal oxidative stress inhibits tumor cell adhesion and enhances experimental
      metastasis of murine mammary carcinoma.
AB  - We have postulated that murine mammary tumor progression is fueled, in part, by
      tumor-associated macrophages that deliver sub-lethal oxidative stress to tumor
      cells. In the present study, we determined whether oxidative stress would affect
      murine mammary tumor cell attachment to laminin and fibronectin, critical
      functions in the metastatic process. Sublethal oxidative stress generated by
      exposure of cells to hydrogen peroxide (H2O2, 1-1000 microM/L) inhibited tumor
      cell attachment to immobilized laminin or fibronectin. This oxidant effect was
      blocked in the presence of catalase which removes H2O2. The inhibitory effect on
      attachment was rapid, with significant inhibition occurring at 5 min; total
      inhibition was achieved at 60 min with 1 mM H2O2. The oxidative stress effect was
      partially reversible at 20 h post-treatment and occurred at concentrations of
      H2O2 that do not adversely affect cell viability or growth. Pretreatment of tumor
      cells with H2O2 or hypoxanthanine and xanthine oxidase (to generate superoxide
      radical and H2O2) prior to intravenous injection, enhanced experimental lung
      tumor colony formation. The enhancement of experimental metastatic potential with
      enzyme-generated oxidative stress was completely reversed by catalase; the H2O2
      mediated enhancement was only partially reversed with catalase. Thus, treatments
      that inhibit tumor cell attachment to extracellular matrix proteins in vitro
      enhance experimental metastasis in vivo.

PMID- 7820954
TI  - Effects of mast cell-macrophage interactions on the production of collagenolytic
      enzymes by metastatic tumor cells and tumor-derived and stromal fibroblasts.
AB  - Histological examination of the metastatic rat mammary adenocarcinoma line MTLn3
      showed that macrophages and mast cells were frequently localized at the tumor
      periphery in the stromal tissues adjacent to the zones of tumor invasion. The
      interactions of these host cells with tumor cells and tumor-associated
      fibroblasts could be important in stimulating the production of extracellular
      matrix-degrading enzymes that facilitate tumor invasion and metastatic spread.
      Therefore, we examined the effects of isolated, activated macrophages and mast
      cells on the secretion of collagenolytic activities by normal fibroblasts,
      metastatic mammary adenocarcinoma cells and tumor-associated fibroblasts. Medium
      from activated macrophages or degranulated mast cells stimulated significant
      increases in production of collagenolytic activities by normal and tumor
      associated fibroblasts and MTLn3 tumor cells. Medium from activated macrophages
      that had been pretreated with medium from degranulated mast cells, however, were
      less stimulatory to fibroblasts and tumor cell production of collagenolytic
      activities than medium from degranulated mast cells alone. We also examined the
      effects of two cytokines, interleukin-1 alpha and tumor necrosis factor-alpha on
      activated macrophage- and degranulated mast cell-stimulation of fibroblast and
      tumor cell collagenolytic activities. The two cytokines alone or in combination
      stimulated increased production of collagenolytic activities by fibroblasts and
      tumor cells. Addition of the cytokines to degranulated mast cell products
      resulted in secretion of higher collagenolytic enzyme activities by normal
      fibroblasts (but not by tumor-derived fibroblasts or tumor cells) than with
      degranulated mast cell product-treatment of either target cell alone. Cytokines
      used in combination with macrophage-conditioned medium were less effective in
      stimulating fibroblast and tumor cell collagenase activities than cytokines
      alone. Thus normal infiltrating host cells such as macrophages and mast cells can
      have profound effects on the production of degradative enzymes by tumor cells and
      tumor-associated stromal fibroblasts.

PMID- 7820955
TI  - Expression of MHC class I and class II antigens in primary breast carcinomas and
      synchronous nodal metastases.
AB  - Expression of the major histocompatibility (MHC) class I and class II antigens
      was studied by immunohistochemistry in a series of 70 primary breast carcinomas
      and in nodal metastases. In particular, the expression of class I (HLA A-B-C) and
      class II (DP, DQ and DR) molecules was compared in: a) primary breast cancers
      devoid of nodal metastases (n = 36) and tumors exhibiting metastatic deposits (n
      = 34) at the time of surgery, and b) primary breast carcinomas and their
      corresponding synchronous axillary nodal metastases. Reduced or absent HLA A-B-C
      antigen expression was seen in approximately 54.3% of primary breast carcinomas,
      whereas a partial or complete induction of class II products was observed in
      18.5% (DQ), 30% (DP) or 48.5% (DR) of the same cases. An almost complete overlap
      of antigen expression was observed in breast tumors in which no metastases were
      found by histological examination of axillary nodes and in neoplasms showing
      histologically-diagnosed synchronous metastases. The reactivity for class I and
      class II antigens in nodal metastases roughly paralleled that exhibited by
      corresponding primary tumors. A discordant expression was seen in 11 cases (32%)
      stained for HLA A-B-C and in 8 (24%), 7 (21%) and 6 (18%) cases assayed for DP,
      DQ and DR products, respectively. When a discordant expression was detected,
      either decreased or increased staining patterns were observed in metastases. The
      finding of overlapping MHC antigenic profiles in the majority of primary breast
      tumors and nodal metastases casts doubts on the hypothesis that loss of MHC
      antigens can play an important role in the seeding and growth of metastatic
      breast carcinoma cells.

PMID- 7820956
TI  - Overexpression and localization of cathepsin B during the progression of human
      gliomas.
AB  - Degradation of the extracellular matrix is a prerequisite for acquisition of the
      invasive phenotype. Several proteinases released by invading tumor cells appear
      to participate in the focal degradation of extracellular matrix proteins. Using
      an enzyme-linked immunosorbent assay, enzymatic assays, Western and Northern
      blotting techniques, we determined whether increased levels of the cysteine
      protease cathepsin B correlated with the progression and invasion of human
      gliomas. The amount of cathepsin B activity and protein content were highest in
      glioblastomas, lower in anaplastic astrocytomas and lowest in normal brain tissue
      and low-grade gliomas. There were significantly higher amounts of M(r) 25,000 and
      26,000 bands in glioblastoma and anaplastic astrocytoma than in normal brain and
      low-grade glioma tissue extracts as determined by Western blotting with anti
      cathepsin antibodies. In addition, cathepsin B transcripts were overexpressed in
      anaplastic astrocytoma (about two- to three-fold), in glioblastoma (about eight-
      to 10-fold), compared with normal brain tissue and low-grade glioma.
      Immunohistochemical staining for cathepsin B showed intense immunoreactivity in
      tumor and endothelial cells of glioblastomas and anaplastic astrocytomas but only
      weak immunoreactivity in low-grade glioma and normal brain tissues. Therefore, we
      conclude that cathepsin B expression is greatest in highly malignant
      astrocytomas, especially in glioblastomas, and is correlated with the malignant
      progression of astrocytomas.

PMID- 7820958
TI  - [The corticospinal tract lesion of amyotrophic lateral sclerosis--magnetic
      resonance imaging of the spinal cord].
AB  - Magnetic resonance imaging by gradient echo method demonstrated lesions of the
      lateral corticospinal tract at cervical cord levels in three ALS patients.
      Patient 1 was a 43-year-old woman with common form of ALS. She developed right
      side predominant pyramidal signs, and right-side predominant prolongation of
      central motor conduction time. MRI showed hypersignal intensity areas in the
      dorsal region of the lateral column at the 4th and 5th cervical segments with
      right-side predominancy. Patient 2 was a 65-year-old man with pseudopolyneurtic
      form of ALS, who showed lower motor neuron signs without a pyramidal sign. MRI of
      the 3rd and 4th cervical cord segments demonstrated bilateral hypersignal
      intensity areas in the dorsal part of the lateral column. Patient 3 was a 62-year
      old man with common form of ALS, who showed marked bilateral pyramidal signs with
      Babinski's sign. MRI of the 5th cervical spinal cord segment demonstrated
      bilateral hypersignal intensity areas in the dorsolateral column. Thus obtained
      MR images of the spinal cord corresponded well to the postmortem-confirmed
      degeneration of the spinal corticospinal tract. MRI of the spinal cord performed
      by gradient echo method would provide additional information on the upper motor
      neuron involvement in ALS.

PMID- 7820957
TI  - Expression of tissue inhibitors of metalloproteinases: negative regulators of
      human glioblastoma invasion in vivo.
AB  - Tissue inhibitors of metalloproteinases (TIMPs) are negative regulators of matrix
      metalloproteinases (MMPs) which degrade major components of the extracellular
      matrix. The aberrant expression of TIMPs is believed to represent an important
      modulating factor in the invasive capacity of human tumors. In the present study
      we analyzed the expression of TIMPs in human brain tumor tissue samples by an
      enzyme-linked immunosorbent assay (ELISA) and by Northern blotting analysis.
      Quantitation of TIMP-1 and TIMP-2 by ELISA demonstrated low levels of TIMP-1 and
      TIMP-2 proteins in glioblastomas, and moderate levels in anaplastic astrocytomas
      compared with normal brain tissues low-grade gliomas and metastatic tumors (renal
      and breast carcinomas and melanomas). Northern blot analysis of TIMP-1
      transcripts demonstrated higher expression in meningioma, normal brain tissues
      and other metastatic tumors than in anaplastic astrocytoma and glioblastoma. Two
      distinct transcripts of 1.0 and 3.5 kb were observed for TIMP-2 mRNA in normal
      brain tissue and in tumor extracts. In addition, TIMP-2 mRNA expression was lower
      in glioblastoma and anaplastic astrocytoma than in meningioma, normal brain
      tissues and metastatic tumors. These findings suggest that down-regulation of
      both TIMP-1 and TIMP-2 contributes significantly to the invasive potential of
      human glioblastoma multiforme and anaplastic astrocytomas.

PMID- 7820960
TI  - [Effects of CDP-choline on dynamic changes in LCBF and cognitive function in
      demented subjects--an H2 15O-PET study].
AB  - We studied correlations of serial changes in local cerebral blood flow (LCBF)
      after single intravenous (i.v.) injection of cytidine diphosphate choline (CDP
      choline) to changes in cognitive function in demented subjects after its daily
      administration for one week. The study group consisted of 7 patients with
      dementia of vascular origin (VD group; mean age 65.0 years) and 3 patients with
      dementia of non-vascular origin (non-VD group; 64.7 years). Cognitive function
      was evaluated with the Japanese version of the Cross Cultural Cognitive
      Examination (CCCE). After i.v. injection of CDP-choline, mean supratentorial LCBF
      increased with the maximum value at 40 minutes post-injection in the VD-group,
      but decreased in the non-VD group (Type, n.s.; Time, n.s.; Type x Time, p < 0.01;
      ANOVA). The number of the pass-tasks in CCCE increased significantly after the 7
      days-injection of CDP-choline only in the VD group (p < 0.05), while it was
      fairly stable in 15 control patients, who were matched in age and severity of
      dementia to the study patients. In this group, a change in the number of pass
      tasks was significantly correlated with those in LCBF at ROIs in the left and
      right temporal cortices and the right thalamus. In the non-VD group, there were
      no significant changes of mean supratentorial LCBF and of the number of pass
      tasks in CCCE. These results may be attributable to difference in availability of
      the acetylcholine neurotransmitter system in the brain between VD- and non-VD
      patients.

PMID- 7820959
TI  - [Double crush syndrome in patients with cervical spondylosis or ossification of
      posterior longitudinal ligament--a clinicophysiological study].
AB  - To clarify the clinical characteristics of double crush syndrome (DCS), we
      evaluated 207 patients with cervical spondylosis (CS) and 19 with ossification of
      posterior longitudinal ligament of the cervical spine (OPLL)
      clinicophysiologically. A diagnosis of DCS was based on the following criteria;
      1) radiological evidence of CS or OPLL on X-ray films; 2) definite spinal cord
      compression on cervical magnetic resonance imaging (MRI); 3) neurological
      deficits in the upper extremities resulting from CS or OPLL; and 4) clinical
      and/or electrophysiological evidence of entrapment neuropathies in the upper
      extremities, namely carpal tunnel syndrome (CaTS), Guyon's tunnel syndrome (GTS),
      and/or cubital tunnel syndrome (CuTS). Pressure-provocative tests were used to
      confirm clinical entrapment neuropathies. Nerve conduction velocities were also
      examined. We found 28 patients with DCS (23 CS, 5 OPLL; 12.8% of all patients).
      There were 9 patients with clinical and electrophysiological DCS, 5 with clinical
      DCS, and 14 with electrophysiological DCS. Of the total number of patients with
      DCS, 21 proved to have CaTS, 4 had CuTS, 1 had GTS, 1 had both CaTS and CuTS, and
      1 had both CaTS and GTS. Definite spinal cord compression was seen at C5/6 (23
      patients), C4/5 (21), C3/4 (13) and C6/7 (10) on cervical MRI. In the majority of
      patients, neurological deficits of the upper extremities did not result from a
      single peripheral nerve lesion. It is well known that a discrepancy between
      neurological manifestation and neuro-imaging sometimes occurs in CS and OPLL, and
      circulatory disturbance in the spinal cord has been considered a possible
      pathogenetic mechanism of the disorder.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7820961
TI  - [A case of sarcoidosis with frequent recurrence of ophthalmoplegia].
AB  - A 72-year-old woman was admitted to our hospital with the complaint of recurrent
      ophthalmoplegia. During three months before her first consultation, she had
      experienced five episodes of ptosis and diplopia, which had lasted for about 1
      month. No significant abnormality was shown with computed tomography (CT),
      magnetic resonance imaging (MRI) and MR-angiography on her brain. Cerebrospinal
      fluid was normal. Serum angiotensin converting enzyme (ACE) level was mildly
      elevated. The enlargement of hilar lymph nodes which showed non-caseating
      epitheloid granuloma suggestive of sarcoidosis was seen with chest X-ray and CT.
      A few days after the treatment of 60 mg of prednisolone every other day,
      ophthalmoplegia disappeared and no recurrence has been observed. Cranial nerve
      involvement tends to be seen commonly in neurosarcoidosis. By contrast, the
      nerves innervating the extraocular muscles are rarely involved. Although
      relapsing course of neurosarcoidosis is well known, no case with frequent
      recurrence of ophthalmoplegia during a few months has been reported.

PMID- 7820962
TI  - [Acute relapsing sensory-dominant polyneuropathy associated with anti-GQ1b
      antibody and autoimmune hepatitis].
AB  - A 43-year-old male with 2 episodes of sensory impairments in four extremities and
      liver dysfunction, developed an acute exacerbation of both sensory impairments
      and liver dysfunction after administration of interferon-alpha. On admission,
      neurological examination revealed a mild distal weakness of four extremities,
      moderate impairment of superficial sensation in hands and severe impairment of
      deep sensation and areflexia in all extremities. Routine laboratory tests were
      normal except for a mild liver dysfunction. His serum was positive for
      antinuclear antibody, but negative for anti-DNA antibody and LE-test. Since he
      was seropositive for hepatitis B (HB) c antibody but seronegative for HBs antigen
      and antibody, HBe antigen and antibody, he was considered to be a seroconverted
      carrier of HB virus. Liver biopsy revealed chronic active hepatitis with marked
      lymphocytic infiltration. CSF examinations were within normal limits. Sensory
      conduction studies of median and sural nerves showed no response, but motor
      conduction studies of median and peroneal nerves were within normal limits. Light
      and electron microscopic examination of biopsied sural nerve disclosed a moderate
      decrease in large myelinated fibers, but not in either small myelinated or
      unmyelinated fibers. Thin-layer chromatography with immunostaining showed the
      presence of anti-GQ1b antibody in his serum. The anti-GQ1b antibody did not react
      with GT1a. Oral administration of prednisolone alleviated liver dysfunction,
      muscle weakness and superficial sensory impairment of four extremities, but not
      in deep sensation.

PMID- 7820963
TI  - [A case of acute disseminated encephalomyelitis with pathologically-proven acute
      demyelinating lesion in the peripheral nervous system].
AB  - We present a case of acute severe demyelination affecting both CNS and PNS with
      pathological evidence. A 62-year-old man presented with acute onset of coma
      preceded by common cold-like symptoms. He was diagnosed as acute disseminated
      encephalomyelopathy (ADEM), and died of brain herniation in two weeks. At
      autopsy, in addition to severe demyelination of the white matter of the central
      nervous system, there was widespread acute demyelinating process in the
      peripheral nervous system. Myelin destruction by macrophage was most conspicuous
      in the spinal nerve root with preservation of the axon cylinder. So far the
      association of hypertrophic demyelinating neuropathy was reported in cases of
      multiple sclerosis. However, there have not been any papers in which substantial
      involvement of both CNS and PNS in cases of ADEM except for the clinical report
      by Amit. Antigenic cross-reactivity between CNS and PNS against myelin proteins
      or other antigens like glycolipid may elicit similar immune responses producing
      demyelination.

PMID- 7820964
TI  - [A case of opsoclonus-myoclonus syndrome associated with anti-central nervous
      system antibody].
AB  - We reported a case of opsoclonus-myoclonus syndrome. A 63-year-old man was
      admitted to Kenwakai Hospital with rapidly progressing symptoms, including
      lumbago, whole body pain, vertigo, nausea, and anorexia. He became bed-ridden
      because of severe vertigo and truncal ataxia. Five days after admission, he
      developed opsoclonus followed by myoclonus and mild disturbance of consciousness,
      but he showed no appendicular ataxia or pyramidal tract sign. He was treated with
      prednisolone, 40 mg/day, which was effective for disturbance of consciousness,
      but opsoclonus and myoclonus persisted. He died of liver dysfunction and
      ventricular fibrillation 3 weeks after onset. Blood examination revealed high LDH
      (1,106 IU/l), Al-P, and gamma-GTP titers. Tumor markers were normal except for
      increase NSE activity (129 ng/ml). The cerebrospinal fluid showed normal cell
      count, 63.9 mg/dl of protein, 7.3 mg/dl of IgG, and normal glucose. A cranial CT
      scan showed an old lacune only. Chest rentgenogram and CT scan revealed
      mediastinal and hilar lymph node enlargement. An abdominal CT scan showed
      multiple low density masses in the liver. Small cell lung cancer associated with
      opsoclonus-myoclonus syndrome was suspected. Western blot analysis revealed that
      his serum reacted with protein in the cerebellum, cerebrum, and dorsal root
      ganglion with a molecular weight of 77 kDa. This is the first time such an
      antibody was ever been detected in patients with opsoclonus-myoclonus syndrome.
      The molecular weights of the antigens previously found by the serum of patients
      with this syndrome, were 55 kDa and 80 kDa in patients with breast cancer, and
      210 kDa in patients with neuroblastoma.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7820965
TI  - [A case of occipital lobe epilepsy following cerebral infarction].
AB  - We report a rare case of occipital lobe epilepsy following cerebral infarction in
      bilateral occipital lobes. The patient is a seventeen-year-old female, who had
      cerebral infarction in bilateral occipital regions a few days after an open-heart
      surgery at 15 years of age. Thereafter she sometimes complained of visual field
      defects and ictal amaurosis. Seventeen months later, she developed a tonic
      seizure with ictal amaurosis, visual field defects and head deviation. On
      admission, results of the neurological examinations were all normal with the
      exception of peripheral visual field defects. Scalp electroencephalographic (EEG)
      findings showed paroxysmal discharges that were more prominent in the frontal to
      parietal leads than in the occipital leads. Sometimes the laterality of
      paroxysmal discharges changed. Her visual defects were diagnosed as psychogenic
      activity by the ophthalmological visual fields test. Simultaneous recordings of
      pattern reversal visual evoked potential (VEP) and electroretinograms (ERG)
      showed normal in 15 minute checks, but prolongation of bilateral P100 latency in
      30 minute checks. These findings suggested that peripheral visual fields were
      disturbed. In this case, EEG findings and the initial symptoms of amaurosis and
      visual fields defect suggested occipital epilepsy following cerebral infarction
      in bilateral occipital lobes. We wish to emphasize that simultaneous VEP and ERG
      recording is a useful diagnostic tool for estimating visual functions.

PMID- 7820966
TI  - [An adult case of basal encephalomeningocele with recurrent meningitis].
AB  - A 35-year-old man developed meningitis for the first time at the age of 23.
      Thereafter, he repeatedly suffered from meningitis for six times before he was
      admitted to our clinic. Each meningitis was preceded by upper respiratory
      infection. Chronic infection in the head and neck, fracture of the skull base,
      liquorrhea, Mollaret meningitis, and acquired immunodeficiency were all ruled
      out. Nasal fiberscope examination revealed a palpating white tumor in the left
      olfactory cleavage. Coronal CT scanning demonstrated encephalomeningocele at the
      left ethmoidal cavity. The encephalomeningocele was surgically repaired and the
      patient has been free from further meningitis. The causal relationship between
      the encephalomeningocele and recurrent meningitis was discussed.

PMID- 7820967
TI  - [Valproate related syndrome of inappropriate secretion of antidiuretic hormone
      (SIADH)--a case report].
AB  - We report an 82-year-old retired man who developed syndrome of inappropriate
      secretion of ADH (SIADH) caused by sodium valproate (VPA). He had been taking VPA
      for treatment of symptomatic epilepsy due to cardioembolic stroke. Although he
      was clinically asymptomatic, he was found to have decreased level of serum sodium
      concentration (128 mEq/l). Association of hyponatremia, normal urinary sodium
      concentration, high urine osmolality and increased concentration of serum ADH
      strongly suggested the presence of SIADH. There were no underlying disorders
      which can cause SIADH, such as malignant neoplasm with autonomous ADH release,
      non-malignant pulmonary diseases and active disorders of the central nervous
      system. Eight days after discontinuation of VPA administration serum sodium level
      increased (142 mEq/l) to the normal level. Then, we started the administration of
      VPA again to confirm that VPA was responsible for developing hyponatremia. As a
      result, he developed SIADH with hyponatremia (128 mEq/l) again, which improved
      after discontinuation of the administration. Therefore, we concluded that the
      SIADH might have been caused by administration of VPA. This is the first report
      on adverse effect of VPA causing SIADH.

PMID- 7820968
TI  - [Unilateral external ophthalmoplegia caused by ipsilateral oculomotor nuclear
      lesion: analysis with diffusion weighted MRI].
AB  - A 49-year-old man who had been suffering from poorly controlled diabetes mellitus
      for 20 years was admitted to our hospital with the chief complaints of diplopia
      and right ptosis. The onset of his symptoms was sudden. On admission, he had
      right palpebral ptosis, upward and left lateral gaze paresis of the right eye.
      Hess screen chart examination revealed paresis of the right superior rectus,
      inferior oblique and medial rectus muscles. T2 weighted magnetic resonance
      imaging (MRI) revealed high intensity area in the medial part of the right
      midbrain tegmentum where the oculomotor nucleus located, and diffusion weighted
      MRI demonstrated high intensity area which corresponded to the oculomotor
      fascicles of the midbrain. The latter represented Wallerian degeneration of the
      fascicles. The diagnosis of small infarction of the right oculomotor nucleus
      presenting ipsilateral external ophthalmoplegia was made. The superior rectus
      muscle is innervated by the neurons in the contralateral oculomotor nucleus, and
      the other external ocular muscles innervated by the third cranial nerve are
      conducted by the neurons in the ipsilateral oculomotor nucleus; therefore,
      unilateral oculomotor nuclear lesion generally causes ipsilateral ophthalmoplegia
      plus contralateral superior rectus palsy. Our case presented here shows that
      there may be such a case with oculomotor nuclear disturbance which masquerades
      with oculomotor fascicular or infranuclear disturbance; therefore, it is
      important to include these lesions in differential diagnosis.

PMID- 7820969
TI  - [An adult case of tethered cord syndrome with lipoma and thoraco-lumbar
      syringomyelia presenting slow progressive muscular atrophy in the lower limbs].
AB  - A 23-year-old man developed slowly progressive muscle weakness from the age of
      10, followed by paresthesia and urinary disturbance. The physical examination
      showed bilateral muscular atrophy in the lower limbs and dissociated sensory
      disturbance below Th8. Although there was normal appearance of spinal X-P, MRI
      revealed conus medullaris at S2 involved thoraco-lumbar syringomyelia with
      extramedullary lipoma. After the operation for laminectomy of L5-S2 and
      untethering without direct surgery for syringomyelia, post-operated MRI exhibited
      definite shrinkage of the syrinx. It suggested that thoraco-lumbar syringomyelia
      in the present case was not congenital anomaly, but secondary outcome to tethered
      cord syndrome.

PMID- 7820970
TI  - [Electroglottographic evaluation of swallowing in Parkinson's disease].
AB  - The feasibility of using electroglottography (EGG) to record and measure aspects
      of swallowing was tested in 31 patients with Parkinson's disease (72.8 +/- 4.8
      years) and 10 control subjects (74.6 +/- 4.4 years). The patients were divided
      into three groups: those feeling dysphagia frequently (D(+), n = 9), those
      feeling dysphagia occasionally (D(+/-), n = 8), and those not feeling dysphagia
      (D(-), n = 14). The instrument delivered a 250 microA, 52 kHz carrier signal to a
      pair of surface electrodes on each side of the larynx at the level of the thyroid
      lamina. Tissue impedance across the neck was recorded via EGG while the
      swallowing of 10 ml of water. Four trials were performed for each subject. Based
      on the analysis of EGG waveform, latency, number of phases and duration were
      measured. In the EEGs of D(+) group, the reproducibility of waveforms was poor,
      while the waveforms of D(-) group and control group showed higher
      reproducibility. The waveforms of D(+) group had significantly longer latency and
      more phases than those of D(-) and control groups. In D(+), the duration was
      significantly longer than that of control group. These results suggest that the
      EGG is a quantitative and noninvasive technique for analysis of swallowing in
      patients with Parkinson's disease.

PMID- 7820971
TI  - [A case of "forme fruste" of tuberous sclerosis having been treated as genuine
      epilepsy].
AB  - A 30-year-old man had signs of a lumbosacral skin plaque, called "shagreen
      patch", and mental retardation. He had been treated as genuine epilepsy for more
      than twenty years. Neither significant abnormalities nor facial angiofibroma
      (adenoma sebaceum) were detected on physical and neurological examinations. Brain
      CT revealed calcified subependymal nodules. A T2-weighted brain MRI presented
      high signal intensity regions affecting the cerebral cortex, which suggested
      tuberous lesions. Echocardiography showed high echoic lesions on the left
      ventricular wall and papillary muscles, suggesting calcification. The case was
      diagnosed as suffering from "forme fruste" of tuberous sclerosis. The three
      criteria typical of tuberous sclerosis (facial angiofibroma, seizure and mental
      retardation) were not satisfied. The "forme fruste" variant is less known,
      because the pattern of involvement varies, and it may clinically simulate genuine
      epilepsy.

PMID- 7820972
TI  - [A case of isolated vagus nerve palsy with herpes zoster].
AB  - A case of isolated vagus nerve palsy with herpes zoster was reported. A 31-year
      old woman was admitted to our hospital with six days' history of difficulty of
      swallowing of fluid and hoarseness with a painful vesicle on the right ear.
      Neurological examination revealed poor elevation of soft palate on the right
      side, but the pharyngeal reflex was preserved. Herpetic vesicles were present on
      the right concha, within posterior wall of the external auditory meatus. No
      facial palsy, loss of hearing and mucosal lesions in the mouth or pharynx were
      present. This is the first case of isolated vagus nerve palsy due to varicella
      zoster infection, showing the distribution of the auricular branch of the vagus
      (Arnold's nerve) in the ear.

PMID- 7820973
TI  - [A case of acute idiopathic pandysautonomia complicated with acute pancreatitis
      and liver injury].
AB  - A case of acute idiopathic pandysautonomia (AIPD) complicated with acute
      pancreatitis and liver injury was reported. A 43-year-old woman acutely developed
      abdominal pain, low grade fever, lymphoadenopathy and generalized erythema in May
      1992. She was found to have autonomic dysfunctions, such as orthostatic
      hypotension, hypohidrosis, paralytic ileus and urinary retention. A systematic
      investigation of autonomic function revealed an impairment of both sympathetic
      and parasympathetic post-ganglionic nerves. Serum concentrations of amylase,
      lipase, elastase 1, and transaminase and amylase creatinine clearance ratio were
      elevated in the early stage of the disease. No significant serological findings
      for viral infections were detected to suggest any special etiology of the
      disease; the symptoms gradually improved, although incompletely, after several
      months from the onset. AIPD complicated with acute pancreatitis or liver injury
      is uncommon. A possible link between undetectable viral infection and AIPD was
      discussed.

PMID- 7820974
TI  - Glucose-induced thermogenesis in patients with small cell lung carcinoma. The
      effect of acute beta-adrenergic inhibition.
AB  - Seven patients with histologically verified small cell lung carcinoma were given
      an oral glucose load of 75 g on two occasions to examine the effect of glucose on
      whole body and forearm thermogenesis with and without acute beta-adrenergic
      inhibition with propranolol. Whole body energy expenditure was measured by the
      open circuit ventilated hood system. Forearm blood flow was measured by venous
      occlusion strain-gauge plethysmography. The uptake of oxygen in the forearm was
      calculated as the product of the forearm blood flow and the difference in
      arteriovenous oxygen concentration. The glucose-induced thermogenesis in the 120
      min following the glucose load was significantly reduced by beta-adrenergic
      inhibition with approximately 50% from 63.9 +/- 5.8 kJ 120 min-1 (mean +/- SE) to
      27.8 +/- 9.8 kJ 120 min-1 (P < 0.01). Almost the entire reduction took place from
      60 to 120 min (P < 0.005). The integrated glucose-induced forearm oxygen uptake
      in the period 60-120 min following the glucose load was significantly reduced
      after beta-adrenergic inhibition from 103 +/- 28 mumol 100 g-1 60 min-1 to 29 +/-
      29 mumol 100 g-1 60 min-1 (P < 0.05). The noreadrenaline concentration in the
      arterial blood was not increased in the baseline period compared to healthy
      elderly; it increased following the glucose load while there was no demonstrable
      increase in adrenaline concentration in the two experiments. It is suggested that
      these patients have increased sensitivity of the beta-adrenergic receptors and an
      early facultative component of the glucose-induced thermogenesis in part takes
      place in the forearm.

PMID- 7820975
TI  - Cerebral vasodilation capacity: acute intracranial hypertension and supra- and
      infra-tentorial artery velocity recording.
AB  - This experiment is the first to compare cerebral vasomotor reactivity in the
      supra- and infra-tentorial regions in baseline conditions and during progressive
      acute intracranial hypertension. The increase in intracranial pressure was
      performed using liquid pressure transmission in two groups of 16 rabbits by
      elevating a saline infusion bottle connected to the subdural space. Cerebral
      microvessel dilation capacity was studied using acetazolamide arterial infusion
      during three stages of 20 min: at baseline conditions, with an intracranial
      pressure value equal to half the diastolic arterial pressure and with an
      intracranial pressure equal to the diastolic arterial pressure. The effects of
      acetazolamide in the basilar artery and in the carotid siphon were simultaneously
      monitored by transcranial Doppler sonography during all the experiments. The
      changes in cerebral vasomotor reactivity occurred with the same intensity and
      latency in both vascular compartments in baseline conditions. The maximum
      amplitude of changes happened 30 s later in the basilar artery than in the
      carotid siphon. When intracranial pressure was above half the diastolic arterial
      pressure, the vasomotor tone began to decrease in the carotid siphon which
      supplies a small region of the rabbit brain, whereas it was maintained in the
      basilar artery. This effect could be explained by brain tissue hypertension.
      Vasomotor reactivity had nearly disappeared in all the cerebral arteries
      investigated when intracranial hypertension was equal to the diastolic arterial
      pressure. These results show evidence of a direct and late effect of acute
      elevation of intracranial pressure on cerebral microvascular tone. This begins in
      the supra-tentorial region but there is an early local effect on the carotid
      siphon due to the brain tissue pressure.

PMID- 7820977
TI  - Growth hormone (GH) treatment in GH-deficient adults: effects on muscle size,
      strength and neural activation.
AB  - The effects of 6 months of recombinant growth hormone (GH) treatment (0.5 IU kg-1
      per week) on muscle size, strength and neural activation (EMG) was studied in
      eight adults with childhood onset GH deficiency (GHD). Before treatment, height,
      body mass (BM) and lean body mass (LBM) of the GHD subjects were significantly
      lower (P < 0.01) from those recorded in eight healthy controls, while no
      significant differences were found between the body mass index (BMI) of the two
      populations. Thigh muscle + bone cross-sectional area (CSAM+B) and lower limb
      muscle plus bone volume (LLVM+B) of the GHD patients were 66.1 +/- 13.7% and 47.6
      +/- 6.8% of those recorded in the controls (P < 0.01), whereas no difference in
      CSA/height2 was found between the two groups. By contrast, LLVM+B/height3 was
      82.0 +/- 19.0% that of the controls (P < 0.05). Similarly, quadriceps muscle
      strength (MVC) of the GHD patients was 63.2 +/- 12.4% that of controls (P <
      0.01), while no significant differences in the force per unit area (F/CSA) and
      per body mass (F/BM) were found. After 6 months of GH treatment LBM increased by
      6.0 +/- 4.2% (P < 0.02), CSAM+B by 14.5 +/- 12.7% (P < 0.01) and LLVM+B by 10.1
      +/- 7.3% (P < 0.01), absolute differences from the normals still persisting.
      However, the LLVM+B/height3 of the GHD patients after treatment was no longer
      significantly different from that of the controls. Quadriceps MVC increased by
      9.8 +/- 12.0% (P < 0.02), differences from the controls being still significant,
      whereas the F/CSA and F/BM did not change. A right shift of the integrated
      EMG/Force relation, with no change in the maximal integrated EMG (iEMG) activity,
      was observed in the patients after treatment. In conclusion, the current study
      shows that adults with childhood onset GHD have a reduced skeletal muscle mass
      and strength which seem to be positively influenced by 6 months of GH treatment.

PMID- 7820976
TI  - The separate and combined effect of leucine and insulin on muscle free amino
      acids.
AB  - The effect of insulin and leucine on amino acid and protein metabolism in muscle
      is not fully understood. To characterize their separate and combined effects on
      free amino acids in muscle and plasma, 11 volunteers received an infusion of
      either leucine (1 g h-1, Group 1) or glucose (20 g h-1, Group 2) for 2 h followed
      by a combination of the two infusions for an additional 2-h period. In muscle
      both the leucine infusion and the leucine plus glucose infusion increased the
      concentration of free leucine significantly, while the sum of the other branched
      chain amino acids (BCAA), of the aromatic amino acids and of the basic amino
      acids decreased. Glucose infusion alone decreased the sum of the essential amino
      acids, the BCAA and the aromatic amino acids. The combination of leucine and
      glucose augmented the decreases, while the concentrations of glutamate, glutamine
      and alanine were unaffected. In plasma the leucine infusion doubled the leucine
      concentration and decreased alanine, valine, methionine, tyrosine, phenylalanine
      and the sum of the aromatic amino acids. Glucose infusion decreased methionine,
      serine, isoleucine and the sum of the essential amino acids and of the BCAA. The
      combination of leucine infusion and hyperinsulinaemia augmented the decreases.
      The plasma concentrations of the keto acids of valine and isoleucine decreased by
      the leucine infusion while the concentrations of the keto acid of leucine and
      isoleucine decreased by glucose infusion. The combination of leucine and glucose
      had an additive effect. These effects are attributed to a specific effect of
      leucine on the other two BCAA and a depression of muscle proteolysis by both
      leucine and insulin, resulting from glucose infusion.

PMID- 7820978
TI  - Magnesium sulphate infusion decreases circulating calcitonin gene-related peptide
      (CGRP) in women with primary Raynaud's phenomenon.
AB  - The effects of two different vasodilating agents (MgSO4 infusion and the calcium
      antagonist nifedipine) on circulating levels of calcitonin gene-related peptide
      (CGRP) were studied in 12 women with pronounced primary Raynaud's phenomenon
      (PRP) and in 12 healthy females. There were no significant differences with
      regard to basal levels of circulating CGRP between women with PRP and the control
      group; median 15.5 (range 10-48) vs. 14 (range 10-69) pmol l-1, respectively.
      However, treatment with MgSO4 infusion significantly decreased circulating CGRP
      in women with PRP only from median 15.5 (range 10-48) to 10 (range 10-110) pmol l
      1) (P < 0.05). On the other hand 14 days of treatment with nifedipine did not
      affect circulating CGRP in either of the investigated groups. Erythrocyte
      magnesium (ery-Mg) levels increased significantly after MgSO4 infusion in women
      with PRP (2.43 +/- 0.13 vs. 2.52 +/- 0.15 mmol l-1, P < 0.05) but not in the
      controls (2.51 +/- 0.24 vs. 2.57 +/- 0.28 mmol l-1, ns). In conclusion, the
      decrease of circulating CGRP after MgSO4 infusion in women with PRP provides
      further evidence that magnesium plays a significant role in the pathophysiology
      of PRP.

PMID- 7820979
TI  - Biphasic pulmonary clearance of 99mTc-DTPA in smokers.
AB  - We measured the pulmonary clearance of 99mTc-labelled diethylene triamine penta
      acetate (99mTc-DTPA) for 3 h in 17 non-smokers and in 16 healthy smokers. We
      found the clearance of 99mTc-DTPA to be well described by a mono-exponential
      equation in 14 non-smokers, the half-life being 66 +/- 17 min (mean +/- SD). In
      all smokers, a bi-exponential equation yielded a significantly better curve fit.
      The half-life of the slow and fast clearance components was 83 +/- 19 and 13 +/-
      4 min, respectively. The relative amount of radioactivity cleared by the fast
      component was 57 +/- 15% and correlated significantly with cumulated tobacco
      consumption (r = 0.58, P < 0.02) and forced expiratory volume in 1 s in
      percentage of predicted value (r = -0.60, P < 0.02). We conclude that smoking
      induces a rapidly clearing pool of 99mTc-DTPA in the lung, the size of which may
      be related to smoking habits.

PMID- 7820980
TI  - Effects of head-up and head-down tilt on the transmitral flow velocities in
      relation to age: a Doppler echocardiographic study in healthy persons.
AB  - To assess whether age modifies the effects of preload on the Doppler indexes of
      left ventricular filling, 10 younger (mean age 31 years) and 10 older (mean age
      53 years) healthy subjects underwent transmitral flow velocity measurements
      following acute changes of venous return produced by head-up and head-down tilts.
      In the horizontal supine position, almost all Doppler indexes differed
      significantly between the groups. As venous return increased from the head-up to
      the head-down position, the peak early and late transmitral velocities, their
      ratio, and the acceleration and deceleration of the early flow increased while
      the relaxation time shortened. These changes did not differ significantly between
      the younger and older subjects. In conclusion, both age and preload have strong
      effects on the Doppler transmitral velocity indexes. The preload-induced changes
      are not modified by age.

PMID- 7820981
TI  - Growth hormone suppression and glutamine flux associated with cardiac surgery.
AB  - Pharmacological doses of growth hormone (GH) in humans and rats increase plasma
      and muscle glutamine values. As major surgery results in a physiological rise in
      serum GH concentration, we investigated whether this physiological increase in GH
      altered glutamine metabolism. Eighteen patients undergoing coronary artery bypass
      graft (CABG) surgery were randomly assigned to receive somatostatin, 100
      micrograms subcutaneously at induction of anaesthesia and 8 hourly for 48 h, or
      placebo. Somatostatin effectively blocked the physiological surge of GH following
      injury but did not affect plasma or muscle glutamine concentrations, which fell
      significantly in both groups. Plasma glutamine decreased by 31% (P < 0.01) and
      28% (P < 0.01) in the control and somatostatin groups respectively. Muscle
      glutamine was reduced 45% (P < 0.001) in the control group and 50% (P < 0.001) in
      the somatostatin group. There was no difference in muscle or circulating
      glutamate, alanine or branched chain amino acid concentrations or in metabolite
      values between the somatostatin-treated patients and the control group. There was
      no relationship between the GH response to surgery and glutamine metabolism
      following major surgery.

PMID- 7820982
TI  - Noninvasive study of left ventricular function and systemic haemodynamics during
      dipyridamole echocardiography stress test.
AB  - Left ventricular function and systemic haemodynamics were noninvasively assessed
      during cardiac stress testing with dipyridamole (0.84 mg kg-1 i.v.) in 10
      subjects (44-61 years) with normal coronary arteries (group 1), and in 14
      patients (46-77 years) with coronary artery disease either without (group 2, n =
      6) or with (group 3, n = 8) echocardiographic evidence for myocardial ischaemia
      during test. Left ventricular wall motion and dimensions, and aortic root
      pressure and flow were obtained by Doppler echocardiography combined with an
      externally traced subclavian artery pulse calibrated with brachial artery
      pressures. Peripheral arterial resistance, total arterial compliance, and aortic
      characteristic impedance were estimated from aortic root pressure and flow, by
      use of a three-element windkessel model of the systemic circulation. Left
      ventricular ejection fraction improved from baseline to peak stress in group 1
      (mean +/- SD: 62 +/- 6% vs. 65 +/- 6%, P = 0.05), whereas it was not
      significantly changed in group 2 (58 +/- 10% vs. 56 +/- 6%) and decreased in
      group 3 (53 +/- 10% vs. 43 +/- 10%, P < 0.05). Otherwise, the haemodynamic
      response was similar in the three groups: heart rate and cardiac index increased
      by at least 30% and 37%, respectively, whereas stroke index and arterial
      pressures were maintained at or slightly above baseline. Peripheral resistance
      decreased by at least 22%, and total arterial compliance and aortic
      characteristic impedance were not significantly altered during test. The
      worsening of wall motion abnormality at peak stress in group 3 was not
      significantly related to the change in systemic haemodynamics. Thus, dipyridamole
      acted predominantly on the arterioles without significantly influencing the large
      systemic arteries. Myocardial ischaemia during test impaired regional and global
      left ventricular function, but did not influence the systemic haemodynamic
      response.

PMID- 7820983
TI  - [Consequences of prolonged use of psychoactive drugs. Substitute natural
      treatment and individual psychotherapy].
AB  - The history of psychopharmacology shows the differences existing between various
      groups of substances, natural, and more recent synthetic ones. At present,
      benzodiazepine anxiolytic agents are being singled out for their abuse and
      addiction potential. There has been a return to and widespread use of traditional
      natural therapies and more modern psychotherapy. Patients are more than every
      wary of synthetic agents. The production of herbal substances is nowdays
      organized on an industrial scale. The properties of "alternative" herbal agents
      are illustrated that have been known for centuries and are now studied with the
      methods of biochemistry. A large number of studies are concerned in several
      countries with the actions of traditional plants. The WHO encourages this
      tendency which in some countries has attained official status in schools of
      medicine, and amounts to a marked reduction in the cost of health. Nevertheless,
      the past and present importance of the research on synthetic drugs (antibiotics,
      and even psychoactive substances) cannot be denied. The attention of science in
      this field is aimed at finding new molecules that are possibly free of addictive
      properties but are effective in behavioral therapy. A recent example is
      buspirone. Finally, a psychotherapeutic method is briefly described. In his
      comment and conclusions the author poses important questions concerning the
      organization of medical and pharmaceutic studies in the near future.

PMID- 7820984
TI  - [Effects of intravenous administration of clarithromycin on plasma levels of
      gastrin and group I pepsinogen].
AB  - Erythromycin and some of its derivatives have prokinetic gastrointestinal
      properties. In addition, erythromycin has been shown to stimulate isolated chief
      cells of the gastric mucosa, and to activate pepsin secretion. The above study
      was aimed at ascertaining in a group of dyspeptic patients whether
      clarithromycin, a structural analogue of erythromycin, is apt to modify certain
      functional parameters of gastric secretion, above all the patterns of gastrin and
      PG-I secretion. A 20-minute intravenous clarithromycin infusion (1.5 mg/kg) in
      fasting subjects has brought about a significant reduction (at 20 and 45 minutes
      from the start of infusion) of circulating gastrin (about 23%) and, after a meal,
      a 69% increase. No change of plasma PG-I level was observed either after placebo
      or after the active substance. These findings suggest that in vivo and at the
      doses used in our experiment clarithromycin has no influence on plasma PG-I
      release and is apt to modify the fasting and postprandial gastrin releasing
      pattern.

PMID- 7820985
TI  - [Telemestein and variations in blood concentrations of lipoprotein A].
AB  - Twenty patients with high serum levels of Lp(a) were randomly treated with 900
      mg/day telmestein or placebo. We found, in those treated with telmestein, a
      significant decrease of lipoprotein (a) serum levels (p < 0.05).

PMID- 7820986
TI  - [Water-electrolyte and acid-base balance in surgery. Problems in the
      postoperative period].
AB  - In addition to metabolic conditions, water-electrolyte and acid-base balance in
      the postoperative period are of major importance for the success of surgery. The
      principal water-electrolyte changes (hyperhydration and hypotonic dehydration,
      hypertonic dehydration, "third space" syndrome, etc.) and acid-base (acidosis,
      and metabolic and respiratory alkalosis) disorders are briefly described as they
      are observed in the postoperative period together with their pathophysiologic
      mechanisms and therapy. The identification and correction of these changes may
      avoid the onset of patterns due to reduced therapeutic surveillance.

PMID- 7820987
TI  - [Neoplastic involvement of the cranial base. Role of computerized tomography and
      magnetic resonance].
AB  - We discussed in this paper the abilities and limits of CT Scan and MR Imaging in
      the diagnosis of skull base tumors. We stressed the role of computerized
      neuroimaging in the characterization and evaluation of the extension of these
      tumor masses involving the skull base.

PMID- 7820988
TI  - [Role of imaging technics in the identification, characterization and staging of
      lung neoplasms].
AB  - The findings in different imaging techniques in the diagnosis of bronchogenic
      carcinoma are discussed in this report. Conventional radiology is useful for
      diagnosis, but is insufficient for characterising and assessing the extension of
      neoplastic masses of the lung. CT and MR imaging are not essential for the
      diagnosis and characterization of these lesions, but they certainly allow a more
      accurate evaluation of staging than normal X-ray examination.

PMID- 7820989
TI  - [Re-evaluation of bronchogenic carcinoma after radiochemotherapy. Role of CT and
      MR].
AB  - The above paper was intended to evaluate the usefulness of CT and MR in the study
      of radiation and chemotherapy induced pulmonary changes. CT proved very useful in
      the evaluation of the remission rates of the tumor and of radiation-induced
      pulmonary effects and, hence to minimize its confusion with malignancies and
      other abnormalities. On the other hand, MR proved very useful in the
      differentiation between post-therapy fibrosis and recurrent tumor at least 13
      months after chemo-radiotherapy.

PMID- 7820991
TI  - [Future at risk for obese children].

PMID- 7820990
TI  - [Clinical use of progestins].
AB  - The development of progestogens from the thirties till now and their main
      clinical uses are considered. Progestogens play an essential role not only in the
      treatment of dysfunctional uterine bleeding and endometrial carcinoma, but also
      in oral contraception and in hormone replacement therapy for menopausal women. In
      the last two cases the attention is focused on the relationship between the use
      of progestogens and the risk of mammary carcinoma.

PMID- 7820992
TI  - Comparison of various transport media for viability maintenance of herpes simplex
      virus, respiratory syncytial virus, and adenovirus.
AB  - Seven viral transport media (VTM) were compared for effectiveness in preserving
      the infectivity of herpes simplex virus (HSV), respiratory syncytial virus (RSV),
      and adenovirus. The media tested were Richards viral transport, sucrose-phosphate
      glutamate (SPG), Virocult, HH medium, tryptose phosphate broth, cell culture
      medium, and Bartel's viral transport. Two laboratory strains of HSV (McIntyre and
      333) and two clinical isolates (A0301 and A0386), comprising two HSV-1 types and
      two HSV-2 types, were suspended in each transport medium, kept at 4 degrees C and
      22 degrees C, and assayed for surviving virus at various times of up to 2 weeks.
      Similar testing was done with RSV Long strain and adenovirus type 2. Of the seven
      media, Richards viral transport, SPG, Virocult, and HH medium, followed closely
      by tryptose phosphate broth, best preserved HSV infectivity at both 4 degrees C
      and 22 degrees C. Analysis of decay rates of RSV revealed comparatively rapid
      decay in SPG and Virocult. Adenovirus was stable in all media and at both
      temperatures tested. These results indicate that viral transport and subsequent
      culture isolation are possible using many different VTMs if transport times are
      kept to a minimum (< 1 day), but if transport extends to longer times, or low
      levels of virus are present in the specimen, Richards viral transport and HH
      medium appeared to be the best overall transport media for the viruses tested.

PMID- 7820993
TI  - Fluoroquinolone resistance among methicillin-resistant staphylococci after usage
      of fluoroquinolones other than ciprofloxacin in Taiwan.
AB  - The antimicrobial susceptibility to norfloxacin, ofloxacin, and ciprofloxacin of
      methicillin-resistant staphylococci isolated before and after the use of
      fluoroquinolones other than ciprofloxacin in Taiwan was studied by the agar
      dilution method. Before the use of fluoroquinolones, 54 isolates of methicillin
      resistant Staphylococcus aureus (MRSA) and 51 isolates of methicillin-resistant
      coagulase-negative staphylococci (MRCNS) isolated in 1983-1985 were all
      susceptible to the three fluoroquinolones tested. Following the use of
      norfloxacin, enoxacin, and ofloxacin, the MIC90s of norfloxacin, ofloxacin, and
      ciprofloxacin against 46 isolates of MRSA collected during 1989-1990 increased to
      64, 16, and 32 micrograms/ml, respectively, and the rates of resistant strains to
      these three agents were 37.0%, 30.4%, and 34.8%, respectively. The MIC90s against
      42 isolates of MRCNS also increased to 64, 8, and 8 micrograms/ml, respectively,
      with 35.7%, 23.8%, and 33.3% resistant strains.

PMID- 7820994
TI  - A multicenter survey of resistance in The Netherlands using the Etest.
AB  - To obtain data about the prevalence of resistance in bacterial isolates causing
      serious infections in the Netherlands, a multicenter survey was carried out using
      the Etest for quantitative susceptibility testing. More than 6000 isolates
      belonging to ten species were tested against eight antibiotics. Moreover, the
      Etest was validated against the agar dilution method and the reproducibility of
      the Etest was studied. In spite of pH differences between the agar plates used
      for Etesting and agar dilution testing, a good correlation (that is 86%-97%
      within log2 dilution steps) was found between both methods. Comparison of Etest
      values of the participating laboratories and the reference laboratory showed >
      80% conformity within 1 log2 dilution step and 90% within 2 log2 dilution steps,
      indicating a sufficient reproducibility of the Etest. Resistance percentages were
      low for most species and antibiotics, relatively high percentages (10%-20%)
      indicating natural insusceptibility rather than development or increase of
      resistance.

PMID- 7820995
TI  - Penicillin resistance among Streptococcus pneumoniae in Europe.
AB  - Penicillin resistance in Streptococcus pneumoniae, which has been occasionally
      described in European isolates since the early 1970s, presently constitutes a
      general problem, although its rate may vary largely between countries and areas.
      Spain and Hungary show the highest rates of resistance and were probably the
      starting point for further dissemination to adjacent and distant countries. In
      Europe, resistant strains belong predominantly to serotypes 6, 9, 14, 19, and 23,
      and are isolated more frequently from pediatric than from adult patients, and
      from respiratory and CSF samples rather than blood. Although penicillin
      resistance in pneumococci is usually a well-recognized problem, some
      difficulties, mainly related to methodologic aspects of in vitro susceptibility
      testing, still subsist for its proper surveillance, but may be overcome through
      the adoption of adequate diagnostic protocols and tools.

PMID- 7820996
TI  - Inoculum effects on Etests and agar dilution minimum inhibitory concentrations.
      Piperacillin and piperacillin-tazobactam against Staphylococcus aureus.
AB  - Inoculum effects notoriously occur with beta-lactamase-positive staphylococci in
      dilution susceptibility tests with substrate beta-lactams. Etests, like dilution
      experiments, demonstrated such effects with piperacillin and, to a lesser extent,
      with its tazobactam combinations. When Etests were used with the recommended
      inoculum of approximately 10(6) colony-forming units (CFU/plate, the minimum
      inhibitory concentrations (MICs) of piperacillin-tazobactam found for beta
      lactamase-positive Staphylococcus aureus isolates resembled those found by agar
      dilution for inocula of 10(4) CFU/spot but were two- to eightfold below those
      found by agar dilution for inocula of 10(6) CFU/spot; MICs of piperacillin itself
      by Etest were about fourfold below even those found by agar dilution with inocula
      of 10(4) CFU/spot. Inoculum effects for beta-lactamase-negative S. aureus were
      minimal by both methods.

PMID- 7820997
TI  - Optimizing testing of methicillin-resistant Staphylococcus species.
AB  - Selection of the appropriate NaCl concentration for test medium for oxacillin
      susceptibility testing of Staphylococcus aureus and coagulase-negative
      staphylococci has been problematic when using different antimicrobial
      susceptibility testing methods. Broth microdilution, using cation-adjusted
      Mueller-Hinton broth + 2% NaCl, is the currently recommended reference method.
      There is currently no recommendation for the addition of NaCl to agar for
      dilution susceptibility tests when Staphylococcus species are tested with
      oxacillin. We examined the effects of adding 0, 2%, 4%, and 5% NaCl to Mueller
      Hinton agar and broth for agar dilution, Etest, and broth microdilution tests.
      The results of these tests were compared with the reference broth microdilution
      results and with the results of a hybridization assay using a mec gene probe. We
      tested 223 strains of staphylococci, 128 of which were mec gene positive and had
      oxacillin minimum inhibitory concentrations (MICs) > or = 4 micrograms/ml. Seven
      strains of S. aureus were mec probe negative but were oxacillin resistant. Seven
      coagulase-negative strains (three S. epidermidis, one S. haemolyticus, and three
      S. simulans) were mec probe positive and were oxacillin susceptible. The MICs for
      oxacillin-resistant strains increased two- to fourfold with the addition of 2%
      NaCl, but the MICs for oxacillin-susceptible strains were unchanged. Major and
      very major interpretative rates ranged from 18.2% to 20.2% for agar dilution and
      Etest without NaCl added to the medium, and these rates decreased to < 1% with
      the addition of 2% NaCl to the medium. The addition of 4% or 5% NaCl caused major
      error rates of > 17% for all test methods.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7820998
TI  - Problems in minimum inhibitory concentration determinations in coryneform
      organisms. Comparison of an agar dilution and the Etest.
AB  - The antimicrobial susceptibility of 159 coryneform organisms was determined by an
      agar dilution and Etest methods. Overall, the correlation between minimum
      inhibitory concentrations obtained by both techniques was good (> or = 0.09) for
      most antibiotics and organisms although the essential agreement ranged from 59%
      to 88.3%. Most organisms were equally categorized (sensitive, intermediate, or
      resistant) by both methods with only 0.2%, 0.4%, and 3.5% of very major, major or
      minor discrepancies, respectively. Such percentages dropped significantly when
      discrepant strains were retested. The correlation was specially good for
      Corynebacterium jeikeium and Corynebacterium urealyticum.

PMID- 7820999
TI  - Application of the Etest to antimicrobial susceptibility testing of Legionella
      spp.
AB  - Development of susceptibility tests for Legionella spp. has been difficult
      because of the specific growth requirements of this organism. The most commonly
      used media, buffered charcoal-yeast extract (BCYE) agar contains charcoal, which
      is known to inactivate some antimicrobial agents. This study compared five
      antimicrobial (erythromycin, clindamycin, ofloxacin, doxycycline, and rifampin)
      minimum inhibitory concentration (MIC) values as determined by agar dilution
      using BCYE, agar dilution using this same media without the charcoal [buffered
      yeast extract (BYE) agar], and the Etest on BCYE media. The MIC50 and MIC90 for
      this group of Legionella spp. were greater with BCYE than with BYE. Erythromycin
      and ofloxacin (fourfold change) were the most affected by the charcoal in the
      medium. The Etest MIC and agar dilution MIC with BYE were comparable. The Etest
      rifampin results demonstrated that the Legionella spp. strains were very
      susceptible (< 0.016 micrograms/ml, producing very large zones) requiring use of
      one half of the Etest strip, a whole test strip on an individual 100-mm plate of
      BCYE, or use of a new low-MIC-range Etest strip. The Etest on BCYE provides a
      simple, readily available, and accurate method unaffected by medium components
      for susceptibility testing of Legionella spp.

PMID- 7821000
TI  - Etest for susceptibility testing of Mycobacterium tuberculosis and Mycobacterium
      avium-intracellulare.
AB  - Methods currently used for susceptibility testing of Mycobacterium, including
      agar dilution and the Bactec radiometric method, are based on the proportion
      technique using a single critical concentration of antibiotic. Preliminary
      studies were conducted with Mycobacterium species by using the Etest method, a
      gradient minimum inhibitory concentration technique, well described for
      susceptibility testing of other fastidious and slow-growing organisms. Excellent
      correlation was demonstrated between Etest and agar dilution with rifampin
      susceptible and -resistant isolates of M. tuberculosis and ciprofloxacin
      resistant and -susceptible isolates of Mycobacterium avium-intracellulare.

PMID- 7821001
TI  - Etest for routine clinical antimicrobial susceptibility testing of rapid-growing
      mycobacteria isolates.
AB  - The Etest has become a widely accepted alternative susceptibility-testing method
      for difficult-to-assess organisms, including rapid-growing Mycobacterium spp.
      Following an internal validation and literature reviews, the Etest was applied as
      the routine method for testing Mycobacterium chelonae and Mycobacterium fortuitum
      isolates. Results from testing 31 strains confirmed the utility of the Etest and
      the simplicity of the procedure. Mycobacterium chelonae were generally more
      resistant to all drugs except amikacin (MIC90, 32 micrograms/ml), compared with
      M. fortuitum strains that were inhibited (MIC50 in the susceptible range) by
      amikacin (1 microgram/ml), ciprofloxacin (0.032 microgram/ml), doxycycline (0.125
      microgram/ml), and trimethoprim-sulfamethoxazole (0.032 microgram/ml). The
      polymyxin-B disk used as an identification method was confirmed (> or = 10 mm =
      M. fortuitum). The Etest provides a simple and accurate method for selecting
      appropriate therapy for infections caused by rapid-growing mycobacteria (a
      typical case report is presented).

PMID- 7821002
TI  - Determinations of minimum bactericidal concentrations, kill curves, and
      postantibiotic effects with the Etest technology.
AB  - The bactericidal activity of antimicrobial agents is generally determined
      following broth dilution minimum inhibitory concentrations (MIC) procedures.
      These methods are cumbersome, require advanced technical experience, and lack
      proven reproducibility. Etest (AB Biodisk, Solna, Sweden) is a predefined
      antimicrobial gradient on a plastic carrier strip that is used to generate a
      precise MIC on an agar plate. A pilot study was conducted to investigate whether
      a drug's bactericidal effect could be assessed by transferring the "growth
      inhibition pattern" from the Etest MIC ellipse onto a drug-free agar plate. The
      transfer was performed using four techniques of replica plating, a filter method,
      drug inactivation, and sampling of growth alongside the Etest strip. Defined
      antimicrobial-organism models were used to determine the minimum bactericidal
      concentrations (MBCs), killing curves (KCs), and postantibiotic effects (PAEs) of
      several drugs. Preliminary results suggest that the Etest provides an alternative
      method for studies determining the MBCs, KCs, and PAEs of various antimicrobial
      agents.

PMID- 7821003
TI  - Chromate-allergic patients challenged orally with potassium dichromate.
AB  - 30 patients who had positive patch tests to potassium dichromate participated in
      a placebo-controlled oral challenge with 2.5 mg chromium given as potassium
      dichromate. 17 reacted to chromate but not to the placebo, 2 reacted to both
      chromate and the placebo, and 4 reacted to the placebo but not chromate. 7
      patients had no reaction. A specific reaction to chromate was most common among
      patients with dermatitis of the hands and/or feet.

PMID- 7821004
TI  - Delayed-type allergenicity of triforine (Saprol).
AB  - The delayed-type allergenicity of triforine (Saprol), 1,4-bis (2,2,2-trichloro-1
      formamidoethyl) piperazine, was studied. In a mass examination of chrysanthemum
      growers among whom triforine was commonly used, the highest rate of positive
      patch test reaction was seen to triforine (17%) among the 7 pesticides and
      chrysanthemum extracts tested. A higher prevalence rate of work-related skin
      symptoms was seen in subjects with a positive patch test reaction to triforine
      (44%) than in those with negative reactions to all allergens tested (15%) (p <
      0.05). 12 subjects (67%) with positive patch test reactions to triforine were
      also positive to dichlorvos (DDVP), with a high kappa coefficient (0.65). The
      grading of guinea pig maximization test to triforine was grade IV (66%), defined
      as "strong". Cross-sensitization between triforine and dichlorvos was also shown.
      The present results confirm that triforine is capable of including delayed-type
      allergy among chrysanthemum growers and of showing cross-reactivity with
      dichlorvos.

PMID- 7821005
TI  - Echographic evaluation with image analysis of irritant reactions induced by
      nonanoic acid and hydrochloric acid.
AB  - Skin reactions to 40% nonanoic acid in propanol (NON) and to 4% hydrochloric acid
      were evaluated by image analysis of 20 MHz B scan recordings (Dermascan C, Cortex
      Technology). 18 women, aged 18 to 45, were patch tested with 24-h application
      time, and clinical and instrumental evaluations were performed at the beginning
      of the experiment, and 24 and 48 h after patch testing. To check possible
      regional variations in reactivity to NON and HCl, both substances were applied 2
      x on the same forearm. As control tests, saline solution, propanol and sodium
      lauryl sulfate (SLS) 3% were applied. Echographic images were processed by a
      program enabling numerical representation of picture data, based on attribution
      of fictional values to the echoes' amplitudes, selection of amplitude bands of
      interest, binary transformation of the image, and calculation of the extension of
      areas reflecting within the same amplitude range. Sonographic recordings were
      evaluated by an amplitude interval marking hyporeflecting parts of the dermis
      (corresponding to edema and inflammatory infiltration), and by a band
      highlighting the entrance echo (epidermis). Our evaluations showed that extension
      of the hypoechogenic area of the dermis increases according to intensity of
      inflammatory reaction for all irritant substances. A clear decrease in
      reflectivity of the epidermis echo at 24 h was visible at SLS patch test test
      sites, whereas at patch test sites performed with NON and HCl, there was a trend
      towards an increase in values of hyperreflecting pixels. No significant
      variations between data recorded at proximal compared to distal skin sites were
      observed for NON and HCl. In conclusion, the echographic technique provides a
      method for quantification of the dermal inflammatory reaction, and also for
      description of skin reactions induced by irritant substances, according to their
      specific epidermal effects.

PMID- 7821006
TI  - Sesquiterpene lactone mix is not an adequate screen for Compositae allergy.
AB  - 70 patients suspected or known to have contact allergy to Compositae were patch
      tested with 0.1% sesquiterpene lactone mix (SL mix) and individual Compositae
      oleoresins. There were no apparent cases of active sensitization by, or irritancy
      from, the SL mix. 6 patients had allergic reactions to both SL mix and Compositae
      oleoresins, while 11 patients had allergic reactions to Compositae oleoresins
      with a negative reaction to the SL mix. In all but 2 of these, Compositae allergy
      was considered clinically relevant. As 0.1% SL mix picked up only 35% of cases of
      Compositae allergy, we do not consider it an adequate screen.

PMID- 7821007
TI  - Contact allergy to 2-hydroxy-5-tert-butyl benzylalcohol and 2,6
      bis(hydroxymethyl)-4-tert-butylphenol, components of a phenolic resin used in
      marking pens.
AB  - 2-hydroxy-5-tert-butyl benzylalcohol and 2,6-bis(hydroxymethyl)-4-tert
      butylphenol were identified as contact allergens in a phenolic resin used as a
      tackifier in the ink of a marking pen, which, after being used directly on the
      skin, caused an acute contact dermatitis on the hand of a 13-year-old boy. The
      patient also reacted to 4-tert-butylphenol-formaldehyde resin (BPF resin) 1% pet.
      included in the European standard series.

PMID- 7821008
TI  - Sensitization to epoxy resin systems in special flooring workers.
AB  - The use of new products in building and public works is increasing, among them
      being special floor coverings containing epoxy resins and derivatives. These are
      used principally in heavily frequented areas, such as shopping precincts,
      hospitals, civic centres, etc., due to their high resistance to wear and tear,
      environmental factors, etc. In the last 2 years, we have studied 15 cases of men
      sensitized to epoxy resin, or derivatives, who worked with special floorings.
      Speed of sensitization, severity of lesions, and localization to the hands, face
      and legs were characteristic.

PMID- 7821009
TI  - Efficacy of skin barrier creams (IV). The repetitive irritation test (RIT) with a
      set of 4 standard irritants.
AB  - An improved human model for the quantification of skin barrier creams (BCs) is
      described. In contrast to the previously published procedure, the back, instead
      of the forearm, and a total of 4 irritants are used. Due to the larger area, 3 BC
      formulations can be simultaneously compared to the control field, which receives
      the irritant only, without BC-pretreatment. On 10 human volunteers, the irritants
      10% sodium lauryl sulfate (SLS), 1% sodium hydroxide (NaOH), 30% lactic acid (LA)
      and undiluted toluene (TOL) were applied via large Finn Chambers for 30 min, 5 x
      during the 1st week and 4 x during the 2nd week. Taktosan Salbe (water-in-oil
      emulsion) and RAWI Speerschutzcreme (oil-in-water emulsion) were applied 30 min
      before contact with the irritants. In order to assess reproducibility and
      interindividual variation, the BC RAWI was tested in duplicate. Irritant
      cutaneous reactions were quantified by 4 parameters: erythema score,
      transepidermal water loss, blood flow volume and stratum corneum hydration by
      measuring capacitance. The results showed marked differences in efficacy.
      Taktosan significantly suppressed irritation by SLS, NaOH and LA, which was
      apparent in nearly all parameters. RAWI caused significant inhibition of SLS
      irritation, and a positive trend against NaOH and LA was observed. Both BCs
      failed against TOL. The results of duplicate testing with RAWI showed good
      reproducibility. The dogma that oil-in-water emulsions are primarily effective
      against lipophilic irritants, and water-in-oil emulsions against hydrophilic
      irritants, needs to be re-evaluated on the basis of our findings. This model
      seems to have potential for further studies on BCs and might elucidate the
      complex interaction of BCs with irritants.

PMID- 7821010
TI  - Hypertrophic allergic contact dermatitis from hair dye.
AB  - We report a case of hypertrophic allergic contact dermatitis probably due to p
      phenylenediamine (PPDA) in a 26-year-old female, which developed at the sites of
      application of a black hair dye to the skin. Histological examination revealed an
      eczematous process. The lesions subsided completely except for leukoderma that
      remained on the leg. Patch tests showed positive reactions to PPDA, p-aminophenol
      and Disperse Orange 3. PPDA, which was one of the components of the dye, was
      considered to be the primary sensitizer because it was the only substance able to
      reproduce at the patch test site both the hypertrophic pattern and the permanent
      leukoderma found in the patient's lesions. To explain the difference in reaction
      between PPDA and the other 2 para-group substances, we speculate that they are
      due to different quantities of reactive intermediates, oxidation products and
      free radicals, produced by these substances.

PMID- 7821011
TI  - Sulfite contact allergy.
AB  - In the last 2 years, 2,894 consecutive eczematous patients were patch tested with
      sodium metabisulfite 1% pet. Positive reactions were elicited in 50 subjects
      (1.7%). All 50 patients were also positive to potassium metabisulfite 1% pet. and
      sodium bisulfite 1% and 5% pet., while only 2 of them were positive to sodium
      sulfite 1% pet. Prick tests and intradermal tests with a sodium metabisulfite
      solution (10 mg/ml) were negative. No flare-ups of dermatitis or patch test were
      provoked by oral challenge with 30 mg and 50 mg of sodium metabisulfite. The
      dermatitis was taken to be occupational in 7 cases. In only 5 out of 43 non
      occupational cases was the positive reaction considered relevant.

PMID- 7821012
TI  - Efficacies of a barrier cream and an afterwork emollient cream against cutting
      fluid dermatitis in metalworkers: a prospective study.
AB  - We compared the point prevalence of cutting fluid dermatitis and transepidermal
      water vapour loss (TEWL) changes in groups of new machinists who (a) used a
      barrier cream; (b) used an afterwork emollient cream; and (c) did not use any
      cream (controls) over a 6-month period. All machinists handled cutting fluid
      (neat mineral oil) during their work. There was no significant difference in the
      prevalence of cutting fluid dermatitis in the 3 groups throughout the study
      period. The prevalence of cutting fluid dermatitis in all groups increased
      rapidly during the first 6 weeks and thereafter remained steady throughout the
      remainder of the study period. The prevalence of cutting fluid dermatitis was
      slightly lower in machinists using afterwork emollient cream compared to those
      using barrier cream and controls (not significant). The differences in the mean
      TEWL changes during the study period among the 3 groups were also not
      statistically significant. The mean TEWL values in the 3 groups increased rapidly
      during the first 6 weeks of exposure to cutting fluids and thereafter remained
      fairly constant throughout the remainder of the study period. Barrier cream and
      afterwork emollient cream did not appear to have any significant effect against
      either cutting fluid dermatitis or TEWL changes in machinists exposed to cutting
      fluid. However, afterwork emollient cream appeared clinically to help reduce the
      prevalence of cutting fluid irritation.

PMID- 7821014
TI  - Fixed drug eruption induced by ciprofloxacin followed by ofloxacin.

PMID- 7821015
TI  - Occupational contact dermatitis from citrus fruits: lemon essential oils.

PMID- 7821013
TI  - 2 years experience of photopatch testing in Singapore.

PMID- 7821016
TI  - Contact allergy to a synthetic tannin in Tannosynt liquid.

PMID- 7821017
TI  - Intolerance and contact allergy to tar and dithranol in psoriasis.

PMID- 7821018
TI  - Evaluation of patch test reactions by evaporimetry and colorimetry.

PMID- 7821019
TI  - An approach to evaluating patch test results.

PMID- 7821020
TI  - Patch test reactivity in young and aged patient groups.

PMID- 7821021
TI  - Contact dermatitis from Fremontodendron.

PMID- 7821022
TI  - Allergic contact dermatitis from fepradinol: report of 4 cases and review of the
      literature.

PMID- 7821023
TI  - Contact allergy to witch hazel.

PMID- 7821024
TI  - Allergic contact dermatitis due to a moisturizing body cream with chitin.

PMID- 7821025
TI  - Dermatitis associated with orthopaedic prostheses and internal fixations.

PMID- 7821026
TI  - Urticarial reaction to ethylenediamine in aminophylline following mesotherapy.

PMID- 7821027
TI  - Allergic contact dermatitis due to furazolidone in a piglet medication.

PMID- 7821028
TI  - Allergic contact dermatitis from Verbena officinalis L.

PMID- 7821029
TI  - Allergic contact dermatitis due to Centella asiatica extract.

PMID- 7821030
TI  - Cytokine production of peripheral blood mononuclear cells, in response to
      stimulation with allergen, as an aid to the diagnosis of contact sensitivity.

PMID- 7821031
TI  - Allergic contact dermatitis from spironolactone.

PMID- 7821032
TI  - Allergic contact dermatitis from propyl gallate.

PMID- 7821033
TI  - Occupational contact dermatitis due to spectinomycin.

PMID- 7821034
TI  - Mercury allergy.

PMID- 7821035
TI  - Topical thiabendazole allergy.

PMID- 7821036
TI  - Gastric carcinoma.

PMID- 7821037
TI  - [IAAS--International Association of Ambulatory Surgery, Orlando 10 May 1994].

PMID- 7821038
TI  - [Attempts to bypass educational requirements].

PMID- 7821039
TI  - [Important changes in the EMB].

PMID- 7821040
TI  - [Protocol for membership meeting of the BDC 6 April 1994 in Munich, Convention
      Center, Congress Hall].

PMID- 7821042
TI  - [Ambulatory surgical therapy of carpal tunnel syndrome].

PMID- 7821041
TI  - [Ambulatory surgical therapy of carpal tunnel syndrome].

PMID- 7821043
TI  - [Somatostatin receptor scintigraphy in preoperative diagnosis of the site of
      endocrine gastrointestinal tumors].
AB  - To determine the value of somatostatin-receptor scintigraphy in the localization
      of various endocrine gastrointestinal tumors, we compared the results obtained
      with this new technique with the results obtained with computed tomography and
      sonography. We could not find an overall advantage of somatostatin-receptor
      scintigraphy as compared to computed tomography or sonography in the localization
      of intestinal carcinoids (n = 13), gastrinomas (n = 12), functionally non-active
      endocrine pancreatic tumors (n = 8) and various other endocrine pancreatic tumors
      (n = 4). In 2 patients with endocrine pancreatic tumors however, the tumors were
      localized preoperatively only by somatostatin-receptor scintigraphy. Somatostatin
      receptor scintigraphy may occasionally be helpful in the localization of
      gastrointestinal endocrine tumors if these tumors are not localized by
      conventional imaging studies. Somatostatin-receptor scintigraphy does not solve
      the problem to localize small endocrine tumors.

PMID- 7821044
TI  - [The functionally inactive endocrine pancreas tumor].
AB  - Endocrine tumors of the pancreas are extremely rare (1-3%). We present two cases
      with functional inactive tumors--one benign and one malignant--, which were
      immunohistologically secreting glucagon without having clinical symptoms.
      Differential diagnosis, operative strategy and therapy of endocrine tumors of the
      pancreas are discussed.

PMID- 7821045
TI  - [Therapy of unilobar Caroli syndrome by liver resection].
AB  - Caroli's disease is characterized by uni- or bilobar cystic enlargement of the
      intrahepatic biliary tract. Clinical symptoms include recurrent cholangitis,
      right upper quadrant abdominal pain and jaundice. The diagnosis is usually
      established preoperatively based on abdominal ultrasound, computertomography and
      ERCP. Eight patients suffering from unilobar Caroli's disease underwent liver
      resection during a period of six years. The postoperative course was uneventful,
      and after a median follow-up of 39.6 months in one case only a temporary jaundice
      occurred. Liver resection is the method of choice for Caroli's syndrome when
      feasible. Apart from the curative intention liver resection represents also a
      prophylactic method since the risk of malignant transformation to
      cholangiocellular carcinoma in the cystic walls after draining procedures is
      considerably high. For diffuse spread of Caroli's disease in the liver orthotopic
      liver transplantation has emerged as therapeutic option.

PMID- 7821046
TI  - [Prognostic improvement by R1 and R2 lymphadenectomy in stomach carcinoma].
AB  - In 1986 systematic R2 lymphadenectomy was introduced into the surgery for gastric
      carcinoma in our institution. In an historic analysis 381 patients of the years
      1980-1992 were investigated. The effect of R2 lymphadenectomy was studied after
      R0 resection and exclusion of inhospital mortality. 81 matched pairs of patients
      with and without lymphadenectomy (LA) were restaged according to the latest
      classification of the UICC (1987) and compared in an univariate and multivariate
      analysis. A significant improvement of the estimated 5-year survival-rate was
      only seen in UICC-stages II (p = 0.05), IIIA (p = 0.01) and patients without
      lymph node metastases (pN0, p = 0.01). The multivariate analysis did not show an
      independent effect of LA on prognosis but of the oncological parameters pT and pN
      (p = 0.0001). We conclude that LA improves the prognosis of gastric carcinoma in
      certain early stages but the effect is not as impressive as expected.

PMID- 7821047
TI  - [Sigmoid diverticulitis in immunosuppressive drug therapy].
AB  - In a retrospective study we evaluated the data of 92 patients (41 women, 51 men,
      age median: 63 years) with diverticulitis of the sigma who were treated
      surgically in our clinic from January 1986 till December 1992. Twelve patients
      (13%) suffered from suppression of the immune system due to a corticoid therapy
      (n = 3), chemotherapy (n = 1), combination of corticoid therapy and chemotherapy
      (n = 1), combination of chemotherapy and azathioprine, leucopenia due to
      carbimazole therapy as a side effect (n = 1) and immunosuppression with
      prednisone, azathioprine and cyclosporine after renal and heart transplantations
      (n = 5). The therapy was Hartmann's procedure in 5 patients, drainage and loop
      colostomy in one patient, sigma resection with primary anastomosis without a
      protective enterostomy in 5 patients and with a loop ileostomy in one patient.
      One patient died in the early postoperative course. Sigma diverticulitis in
      immunosuppressed patients is a well-known problem especially in large clinics
      with organ transplantation units. In contrast to reports from up to the eighties
      we found no significant difference in the postoperative morbidity and mortality
      after surgical treatment of acute sigma diverticulitis in immunosuppressed
      patients compared to non immunosuppressed patients.

PMID- 7821048
TI  - [Classification of inguinal hernias].
AB  - Classification of inguinal hernia is a necessary prerequisite for a reliable
      analysis of different methods of repair. The underlying categorization is done
      intraoperatively based on the localization ('M' medial, 'L' lateral, 'F' femoral)
      and transverse diameter (I = < 1.5 cm, II = 1.5-3.0 cm, III = > 3.0 cm) of the
      hernial orifice. In cases of combined hernias the diameters of both fascial
      defects is added up, the hernia is classified according to the part of major
      importance for the development of recurrences, the medial defect, with the index
      'c'. The classification can be applied to open as well as laparoscopic
      approaches. The diameters of the tip of the index finger or the length of branch
      of endoscopic scissors (1.5 cm), respectively, serve as standards for
      measurement.

PMID- 7821050
TI  - [Colpotomy for specimen removal in laparoscopic surgery].
AB  - The removal of the specimen is one of the major problems in laparoscopic colon
      surgery. In two female patients we have found a solution in the colpotomy. It is
      easy to perform and hardly recognized by the patient. Other large specimen as a
      kidney or spleen can also be removed this way. An elongation of an incision in
      the abdominal wall can be avoided. The pneumoperitoneum is preserved by a special
      clamp for the extraction via colpotomy. The removal of a specimen via colpotomy
      is a conclusive step towards, minimal invasive surgery'.

PMID- 7821049
TI  - [Thoracoscopic localization of intraparenchymal pulmonary coin lesion using
      intraoperative ultrasound].
AB  - Generally, thoracoscopic resection of peripheral round lesions of the lung is a
      viable alternative to open surgery. However, due to the lack of tactile
      sensitivity intraparenchymal lesions often escape thoracoscopic detection and
      therefore this approach is limited to superficial lesions. The use of
      thoracoscopic endosonography may be valuable to localize intraparenchymal lesions
      which are not visible and enable subsequent thoracoscopic wedge resection.

PMID- 7821051
TI  - [Papillomatosis in a bile duct cyst in an adult].

PMID- 7821052
TI  - [Eccrine spiradenoma of the thoracic wall with ulceration and hemorrhage].
AB  - We report a patient who underwent resection of a bleeding ulcerated eccrine
      spiradenoma of the anterior thoracic wall. Malignant transformation and surgical
      therapy of the tumor are discussed.

PMID- 7821053
TI  - [Juvenile arteriosclerosis: rare cause of generalized dilatative and stenosing
      vascular disease].
AB  - In addition to generalized arteriosclerosis connective tissue disease, systemic
      vasculitis as well as genetic metabolic disease are described to be the cause of
      stenotic and aneurysmatic vessel wall alteration. Although these causes are
      rather unusual, they must be considered for the diagnosis of a generalized
      vascular disease with arterial occlusion as well as aneurysm formation to
      determine the appropriate procedure for the individual. Whereas operative
      treatment should be avoided as far as possible for patients with Behcet's disease
      or Marfan syndrome, it is rather indicated for any kind of juvenile
      arteriosclerosis with arterial stenosis as well as dilatation. In this way the
      patient described in the following could be treated successfully by operation
      even though the cause of the juvenile arteriosclerosis was inexplicable, and in
      addition to local complications also the threatening rupture of the aneurysm
      could be controlled.

PMID- 7821054
TI  - [Laparoscopic management of a Spigelian hernia].
AB  - The Spigelian hernia occurs where the vertical linea semilunaris, along the
      lateral border of the rectus muscle, joins the linea semicircularis. The hernia
      lies in the soft tissue under the aponeurosis of the oblique abdominis muscle;
      incision of that layer can be avoided by laparoscopic techniques. In this case
      the hernial canal was closed, firstly with single titanium staples, and secondly
      with a continuous laparoscopic suture using resorbable material. In suspicious
      cases laparoscopy should be performed to confirm the diagnosis of a Spigelian
      hernia. Laparoscopic hernial repair should be evaluated by further usage of this
      technique.

PMID- 7821055
TI  - ["Surgical congresses and publications--is less more?"].

PMID- 7821056
TI  - [Evaluation of the cost effectiveness and quality of hospital treatment: the
      American Medicare Peer Review Organization model].

PMID- 7821057
TI  - [Comment on the contribution "Civil and legal responsibility of the physician in
      failure to prevent thrombosis in post-hospital and ambulatory care" by K.
      Ulsenheimer].

PMID- 7821058
TI  - [The so-called "minor hand injury" and its socioeconomic sequelae].
AB  - A study was carried out involving 167 patients who had received primary treatment
      in alio loco for injuries diagnosed as 'minor cuts, twists and sprain', and who
      were then seen in the out-patient department at a later date. The patient group
      was analyzed with regard to the following: a more precise identification of the
      initial injury, the initiated treatment regimen and more particularly, the socio
      economic consequences of the injury. Duration of treatment programmes, loss of
      working days and compensatory payments were cost-analyzed. The results showed
      that a delayed primary surgical intervention was possible in only 17% of cases,
      it was necessary to alter the treatment regimen in 29% and in 28% it was no
      longer realistic even to initiate treatment. Comparisons between this population
      and a group of a patients who had received adequate primary care showed that in
      the study group length of treatment and days lost at work was prolonged by the
      factor 1.3; furthermore the number of cases in which the reduction of working
      ability was 20% and more was increased by 2.7. Increased costs incurred by
      financial compensations were approx. DM 27,000/patient.

PMID- 7821059
TI  - [Results of "expanded" arthrolysis of the knee joint].
AB  - This report shows the results of 20 patients, suffering on severe knee stiffness,
      who were treated between 1980-1989 at the Berufsgenossenschaftliche Unfallklinik
      in Tubingen with an expanded knee arthrolysis. The knee stiffness of all patients
      was caused by trauma (65% polytrauma) or infection. More than 2/3 of the patients
      (70%) had a preoperative degree of motion which was less than 60 degrees. In
      average 9 months after the initial trauma the expanded knee arthrolysis was
      performed. The arthrolysis was in most of the cases (n = 15) combined with a
      supracondylar correction osteotomy. The average preoperative range of motion from
      (ext./flex.) 0-15-62 degrees has postoperatively been increased to (ext./flex.) 0
      5-92 degrees which corresponds to a relative improvement of motion of 43%. Eleven
      patients showed good or fair results. The prognosis of knee stiffness is
      influenced by the etiology, the pre-operative loss of motion and the period of
      time between initial trauma and arthrolysis, and as well by the intraoperatively
      achieved range of motion and the post-operative application of continuous passive
      motion. The expanded arthrolysis of the knee is a usefull instrument in the
      therapy of severe posttraumatic knee stiffness.

PMID- 7821060
TI  - [Prevention of para-articular ossifications after endoprosthetic hip joint
      replacement by postoperative irradiation].
AB  - In a prospectively randomized study, 137 patients with 141 hips at high risk for
      heterotopic ossification (HO) received prophylactic radiation therapy (RT).
      Patients were randomly assigned to a low-dose regimen of five fractions of 2 Gy
      each (n = 73) or a high-dose regimen of either 10 fractions of 2 Gy each (n = 7)
      or five fractions of 3.5 Gy each (n = 61). Treatment outcome was assessed by
      comparing immediately postoperative radiographs with radiographs obtained at
      least 6 months after hip surgery (Brooker grading score). Positive responses (ie,
      effective prophylaxis of HO) were seen in 129 (91.5%) hips. Treatment failures
      were observed in 12 (8.5%). Use of a nonsteroidal antiinflammatory drug (NSAID)
      lowered the failure rate in both groups. High RT dose with a short duration (< or
      = 9 days) and use of an NSAID was significantly (p = 0.009) correlated with
      treatment success. RT delivered within a few days after hip surgery is effective
      in preventing HO, even in high-risk patients, and provides an alternative of at
      least equal value for patients with contraindications to long-term medication
      with either NSAIDs or corticosteroids.

PMID- 7821061
TI  - [Arthroscopic distension irrigation in acute postoperative infection of the knee
      joint--long-term follow-up].
AB  - Between 1983 and 1993, 26 patients, 12 patients from our clinic and 14 referred
      patients, had to be treated because of a septic knee joint following open
      ligament repair or subsequent arthroscopic surgery. Immediately after
      arthrocentesis for synovial-fluid analysis a distension-irrigation system was
      established under arthroscopic control as described by R.W. Jackson. Three tubes
      were placed into the knee joint cavity. One was used for inflow and the other two
      for outflow. Distension was performed by open inflow and closed outflow tubes
      each second hour for 10 to 15 min. Systemic antibiotics were administered. In 22
      aspirated materials the cultures revealed bacteria: mostly staphylococcus aureus
      (65%). In two cases in which irrigation of the knee-joint infection was performed
      later than the 10th postoperative day a relapse of the infection occurred and
      required a complete debridement and synovectomy. During follow-up period three
      patients underwent second look arthroscopy due to meniscus tear, rupture of an
      ACL reconstruction and synovial proliferation. 7 +/- 3 (2-13) years after
      treatment, 24 patients were re-examined, all had x-rays and 11 patients had a MRI
      of the knee joint additionally. 19 patients showed excellent or good results: no
      complaints, full ROM, no signs of osteoarthritis on x-rays and nearly normal
      participation in sports 4 out of 11 patients had signs of cartilage lesion and
      synovial proliferation. This retrospective study indicates that the distension
      irrigation system is successful only in early acute cases of knee-joint
      infections of postoperative origins.

PMID- 7821062
TI  - [Results of transgenicular amputation with dorsal skin-muscle flap-plasty in
      patients in the final stage of arterial occlusive disease].
AB  - A modified technique of knee joint disarticulation by using a dorsal
      musculocutaneous flap of the gastrocnemius muscle was first described in 1985.
      The retrospective operative results in 60 patients with gangrene due to
      peripheral vascular disease (mean age 69 +/- 12 [43-93] years, 29 female, 31
      male) with 62 knee disarticulations are reported. After a mean survival period of
      18 (1-53) months 47% (n = 28) of the patients had died due to cardiopulmonal
      reasons after a mean follow-up period of 26 (3-71) months. In-hospital 48 day
      lethality was 10%. 9 patients (15%) were re-amputated at above-knee level and in
      5 patients operative revisions of the soft tissue were performed. After discharge
      from hospital 29 of 54 patients (54%) were able to walk with the aid of a
      prosthesis. We conclude that knee disarticulation with the use of a myocutaneous
      gastrocnemius flap is a safe and functionally acceptable operative method in high
      risk vascular patients.

PMID- 7821063
TI  - [Intraoperative leg length measurement in total hip endoprosthesis].
AB  - Preservation or restoration of the equal length of both legs after total hip
      arthroplasty is best achieved by direct intraoperative measurement. The measuring
      instruments designed for this purpose are presented and their application
      described for the posterior approach to the hip. The instruments are easy and
      quick to use. They can also be used for other approaches to the hip and in
      addition they are a valuable aid when estimating the angles of anteversion and
      inclination of the acetabular component. The high degree of accuracy and the
      significant improvement in results when this instrument was used intraoperatively
      was confirmed by comparison of radiographic measurements of two operation series.

PMID- 7821064
TI  - [Treatment of the ipsilateral femur shaft and femur neck fractures with the
      Russell-Taylor reconstruction nail].
AB  - Eleven ipsilateral neck and shaft fractures of the femur in 11 patients (4
      females, 7 males) were treated between May 1987 and December 1990 at the
      Department of Orthopedic Surgery. University of Louisville, Trauma center level
      one. The mean age was 34.5 (16-60) years. All patients sustained their injuries
      from high energy trauma (8 traffic accidents, 3 falls). All neck fractures were
      closed and there were 8 closed and 3 open (grade I, grade II, grade IIIA = one
      each) shaft fractures. All fractures were operated on the fracture table and all
      were stabilized with the Russell-Taylor reconstruction nail. Thus, antegrade
      reamed nailing of the shaft fracture was followed by internal fixation of the
      neck fracture with 8.0 mm and 6.4 mm lag screws. Those were placed with a
      targeting device through the proximal locking holes of the nail. Then, the distal
      locking bolts were implanted by free hand technique. The mean follow-up was 36.2
      (18-71) months. All fractures of the neck and shaft healed. There was no necrosis
      of the femoral head. No infection was observed. The mean healing time for the
      neck fractures was 13.4 weeks and 16.8 weeks for the shaft fractures. In one case
      autogenous cancellous bone grafting was performed in delayed healing of a shaft
      fracture. There were no varus or valgus malangulations. Five patients had a minor
      limited ROM of the hip joint, another 6 patients an average shortening of 1.3 cm
      of he involved leg. In one case a locking bolt had to be removed due to
      loosening.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7821065
TI  - [The AO external clamp fixator. New techniques in external stabilization of
      tibial fractures].
AB  - A serious disadvantage of conventional external fixators is the opening of the
      medullary canal. This creates a direct communication between the canal and the
      exterior. The new pinless external fixator does not have this disadvantage. The
      clamps of the new fixator system do not penetrate cortical bone, they simply rest
      on the cortical surface. The clinical indications of this easily managed system
      are fractures of the tibial shaft in cases in which primary internal fixation is
      precluded either by precarious local or general conditions, or even by a lack of
      infrastructure. In such situations the pinless external fixator is an excellent
      device to achieve a good fracture stabilisation rapidly, while leaving open all
      subsequent alteration of treatment. In case of secondary change to an
      intramedullary nail the pinless fixator facilitates the procedure, because this
      fixator can be also used as an distractor during nailing. Furthermore this
      fixator can be combined with any intramedullary nail to increase the stability in
      case of very proximal or distal as well as highly instable shaft fractures. The
      clamps of the pinless external fixator set are used in combination with the
      standard AO fixator system.

PMID- 7821066
TI  - [The pre-positioned intracutaneous suture--a method for treatment of soft tissue
      defects after fascia splitting in acute compartment syndrome].
AB  - In the treatment of the acute compartment syndrome open fasciotomy gives rise to
      a wide soft tissue opening. The persistence of this opening prevents a timely
      change to internal osteosynthesis in case of additional fractures usually treated
      by a fixateur externe. Closure of the skin defect itself requires additional
      surgery. The cosmetical results particular in cases of a mesh-grafting are
      unsatisfactory. After open fasciotomy the prepositioned intracutaneous suture is
      a simple operation technique leading to early wound closure with a good
      cosmetical result.

PMID- 7821067
TI  - [Traumatic aneurysm of the axillary artery, a rare and severe complication of
      anterior shoulder dislocation].
AB  - The course of pseudo-aneurysm of the axillary artery, rarely occurring after
      blunt trauma of the shoulder, is analysed. Own experience is reported, the
      literature is reviewed. A high index of suspicion is necessary to recognise and
      repair this serious vascular injury in time in order to avoid permanent brachial
      plexus deficiency.

PMID- 7821068
TI  - [Traumatic pseudoaneurysm of the axillary artery after shoulder dislocation].
AB  - By means of a case report the diagnostic and therapeutic procedures and prognosis
      of a pseudo-aneurysm of the axillary artery after shoulder dislocation are
      demonstrated. The diagnosis of aneurysms of the axillary artery is difficult in
      some cases. It is important to mention a possible vascular injury in case of
      close reduction of the shoulder. Therefore in all patients with a penetrating or
      blunt trauma of the shoulder or the upper arm a thorough neurovascular
      examination is required. In patients with neurologic deficits or alteration of
      the pulse a duplex ultrasound examination should be performed and in dubious
      cases an additional arteriography is indicated.

PMID- 7821069
TI  - [Alkaptonuria and ochronotic arthropathy. Arthroscopic and intraoperative
      findings in implantation of a knee joint surface replacing prosthesis].
AB  - Alcaptonuria is a rare (incidence approx. 1:10(6)), autosomal-recessive
      transmitted metabolic disease. The basic defect is a lack of the enzyme
      homogentisic acid oxidase. During metabolism of phenylalanin and tyrosin to
      fumaric acid and acetoacetic acid this enzymatic defect causes an accumulation of
      the intermediate breakdown product homogentisic acid in bradytrophic tissues
      resulting in pigmentation and calcification of the intervertebral disks. We
      present a 57 year old female patient in whom we diagnosed alcaptonuria by the
      appearance of the typical symptom trias homogentisic acid excretion in the urine,
      ochronosis and arthritis. The anamnesis and results of a knee arthroscopy,
      radiographic and laboratory examinations as well as the intraoperative and
      histological findings during implantation of a knee joint surface replacing
      prosthesis (Gemini-System, Link Co., Hamburg, Germany) are reported.

PMID- 7821070
TI  - [Preventing blood transfusion in a severely burned Jehovah's witness].
AB  - The treatment rationale of a burn victim (35% TBSA) who was child of Jehova's
      witnesses is described. Following a combined approach including erythropoetin and
      blood saving surgical techniques we were able to excise and graft the burn areas
      without blood transfusion. An extremely low hemoglobin of 3.4 g/dl was tolerated
      postoperatively and showed an increase to 10.9 g/dl 25 days later when the child
      was dismissed from the burn unit in stable condition. Possibilities to minimize
      blood loss and to avoid blood transfusions are discussed.

PMID- 7821071
TI  - [Instability of the shoulder joint in the athlete].
AB  - In all shoulder instabilities it is very important to classify the type of
      instability precisely in order to choose the right form of therapy and predict
      the results. The acronyms TUBS, which means traumatic instability,
      unidirectional, Bankart lesion, and good response to surgery, and AMBRI, which
      means atraumatic aetiology, multidirectional, and good for rehabilitation,
      represent the complete range of possible instabilities. We discuss the subtypes
      in the differentiation of various instabilities and the different causes and
      pathologies for instability, the clinical and radiological tests possible, and
      the different surgical treatment options, as well as the results in the
      literature. A modification of the Bankart procedure and the arthroscopic Caspari
      capsulorrhaphy procedure for traumatic instabilities are described. The capsular
      T-shift by Neer and Foster is explained as a surgical treatment for
      multidirectional instability.

PMID- 7821072
TI  - [Rupture of the anterior cruciate ligament in the athlete].
AB  - Athletic trauma is the main cause for rupture of the anterior cruciate ligament
      (ACL). In order to regain joint stability and return to unrestricted sports
      activities operative management is indicated. The patella tendon autograft with
      bone plugs on each end is presently the most commonly used graft to reconstruct
      the ACL. The concept of synthetic augmentation was developed for protection of
      the biological tissue during revascularization and remodeling. We use as
      augmentation device the TETRA-L3, which is a 3-mm-wide and 1-mm-thick Trevira
      braid. The function of the composite graft, which is sufficiently strong to allow
      early stress, is based on the principle of load-sharing. Isometric placement of
      the graft without impingement is achieved by using the miniarthrotomy technique
      and specially designed drill guides. Graft fixation is performed with ligament
      staples. An accelerated rehabilitation program emphasizing full extension and
      weight bearing follows. The total rehabilitation program we recommend-
      preoperative rehabilitation, a reliable surgical procedure, postoperative
      rehabilitation, and the patient's return to activity--is a team effort. A
      detailed follow-up evaluation of 41 athletes with ACL reconstruction using a
      central patellar BTB graft and synthetic augmentation with the TETRA-L3 showed
      that restoration of stability (KT 1000 testing, maximum manual excursion, < 3 mm
      difference) and full ROM, muscle strength and power (> 85% of the uninvolved
      knee) and functional capacity (Hop index > 90%) are the main prerequisites for
      sports activities at the desired level.

PMID- 7821073
TI  - [Acute injury to the lateral ligament of the ankle joint in the athlete].
AB  - The ankle sprain is one of the most common injuries in sports. It is useful to
      classify the grade of injury clinically. Stress x-rays, stress ultrasound or
      radiographic examinations are not necessary. Based on the analysis of 24
      controlled studies we conclude that functional treatment is sufficient. It does
      not lead to higher subjective or objective instability nor to a greater number of
      reinjuries. Functional treatment has no complications. Although controlled
      studies about the treatment of athletes are missing, but there is no reason for a
      different treatment in athletes.

PMID- 7821074
TI  - [Muscle and tendon injuries in the athlete].
AB  - Muscle and tendon injuries are the most common injuries in sports; they are
      mostly caused by overuse and repetitive strain injuries and require special
      diagnosis and treatment. Selective examples are given of surgical therapy (when
      conservative treatment fails) for the most frequent sports injuries (like muscle
      ruptures, jumper's knee, Achilles tendon ruptures, rotator cuff tears,
      tendinitis, dislocation of tendons, compartment syndrome).

PMID- 7821075
TI  - [Complications and errors in use of the gamma nail. Causes and prevention].
AB  - The analysis of 310 cases of fractures of the femur, treated with a Gamma-nail
      osteosynthesis, done in two clinics for trauma surgery in Vienna, revealed to a
      high number of complications. For this reason we decided to start an evaluation
      aming at complications in connection to this type of treatment, with 440 patients
      treated over a five year period. We observed 148 complications, which will be
      described. The intraoperative failures were as follows: False drilling during the
      interlocking procedure 64, wrong length of lag screw 13, breakage of the drill
      bit during interlocking procedure 7, additional shattering of shaft 5, external
      malrotation of diaphysis (> or = 20 degrees) 6, internal malrotation of the
      diaphysis (> or = 20 degrees) 1, elongation of diaphysis (2 cm) 1, mistakes in
      using the proximal nail-plaque 4, breakage of bone elevator, used for reduction
      procedure 1 and 1 failure at the target-device during nailing. The complications
      during the postoperative treatment were: Infection 11, perforation of lag screw
      towards cranial 10, towards central 2, migration of the lack screw within the
      femoral head 7, diaphysial fracture at the distal end of nail 6, movement of
      interlocking bolts 4, osteolytic process at fracture site 2 and 3 haematomas,
      needing a revision. Most of these reported complications were due to technical
      failures, lack of experience or inadequate treatment modality. The specifications
      and descriptions should give information about the reasons of these
      complications, but it is the purpose of this publication too, to figure out the
      technical errors which were responsible for most of the complications described.

PMID- 7821076
TI  - [Gamma nail osteosynthesis of per- and subtrochanteric femoral fractures. 4 years
      experiences and their consequences for further implant development].
AB  - The Gamma nail can be used in all types of per- and subtrochanteric fractures
      because of its biomechanical characteristics. In this prospective evaluation of
      our 330 patients treated between November 1989 and November 1993 the usefulness
      of the Gamma nail for the osteosynthesis of all types of fracture was evaluated.
      The rate of intraoperative and postoperative complications but also gait
      function, postoperative weight bearing, general complications, and survival were
      analysed. We compared the results of four therapy periods to evaluate the
      importance of the expertise of the surgeon and the 'learning curve'. The Gamma
      nail osteosynthesis was performed in 72-98% in unstable per- and subtrochanteric
      fractures. The nail diameters used shifted to the 12 mm nail (99%) and the 130
      degrees angle (93%) in the fourth examination period. The intraoperative
      complication rate is highly dependent from the expertise of the surgeon and the
      experience with the system. The rate decreased from 42.2% in the first to 17.2%
      in the fourth examination period. The most important complications were:
      additional fractures (1.7%), distal locking screw problems (7%), femoral head
      rotation (2,4%), and not sufficient fracture reduction (4.1%). Whereas in general
      these did not influence the postoperative management the use of a too short
      femoral neck screw lead to instability. Postoperative local complications were:
      rotation of the femoral head and neck (0.6-5.5%), related to the gliding of the
      neck screw (0.6-4%), fracture at the end of the nail (1.8-4%), fatigue break of
      the nail (1 case) and hematoma (1.2-8.3%). In all these cases reoperation was
      needed. To reduce the rate of intra- and postoperative complications a new
      gliding nail (GN) is presented. Due to the double T-profile of the femoral neck
      blade the implant is stable for neck rotation. The blade has a collar which makes
      it impossible to implant the blade to deep in the femoral neck. The larger nail
      profile at the femoral neck perforation reduces the risk of implant failure. The
      implant can be used as dynamic compression as well as static implant both in the
      direction of femoral neck and shaft.

PMID- 7821077
TI  - [Structure of the axis--key to the etiology of the dens fracture].
AB  - Fractures of the dens are seen especially in young adolescents but also in
      individuals after the sixth decade of life. The etiology of these fractures and
      the occurrence of non-union after initial treatment is still discussed
      controversially. To address these issues, the axis was removed from thirty-seven
      autopsy cases for histomorphometric analysis. The base of the dens is a region of
      least resistance for fractures due to its reduced trabecular bone volume, a
      poorer trabecular interconnection and a cortical thickness one third that of the
      axis. In all of the cases, trabeculae disconnected from the trabecular lattice,
      and in 30% microcallus formations were demonstrated in the base of the dens. In
      osteoporotics the microarchitectural differences of cancellous bone between the
      base of the dens and the other regions of the axis are increased markedly. The
      obtained data suggest that the bone structure of the axis is responsible for the
      location, the distribution and the frequency of fractures of the odontoid
      process. The deficiency of bone mass within the base also offers a new
      explantation for the occurrence of non-unions even after treatment of fractures
      of the base of the dens.

PMID- 7821078
TI  - [Therapy of unstable sacrum fractures in pelvic ring. Results of of
      osteosynthesis with early mobilization].
AB  - Eight patients with sacrum fractures combined with pelvic ring fractures type C
      were treated using a triangular osteosynthesis after reduction of the fracture.
      The additional vertical stabilization between the lumbar spine and the posterior
      iliac crest caused the stability, which is necessary for immediate mobilization
      of patients. Perfect reduction, correct positioning of the hardware, gentle soft
      tissue treatment, as well as early mobilization of the patient, increases the
      early and late prognosis considerably, and compensates the operative trauma
      completely. We observed no infections or redislocations. The described operative
      treatment is state of the art at our institution.

PMID- 7821079
TI  - [Diagnosis, therapy and prognosis of Pipkin fractures (femur head dislocation
      fractures)].
AB  - Fractures of the femoral head combined with a dislocation of the hip are rare
      injuries. In the period from 1975 to 1993 nine of our 231 operatively treated
      patients who had a hip injury sustained a Pipkin fracture. According to the
      history of our patients and the results of the last 18 years we discuss the
      possibilities of diagnosis, treatment and prognosis of the fracture of the
      femoral head with dislocation of the hip.

PMID- 7821081
TI  - [Functional healing of compartment syndrome of the tibia. An analysis of follow
      up results].
AB  - In a retrospective review 78 compartmental syndromes, treated between 1980 and
      1988, were analyzed. The mean follow-up was 42 months. 43 patients (53%) suffered
      an traffic accident. Direct trauma forces predominated (66 patients). The
      functional results after crush injuries had been worser than after contusion
      injuries or direct trauma forces. The functional results depended from the
      posttraumatic interval of decompression. The later the fasciotomy the worser the
      functional results had been. A wide fascial decompression is necessary. Two cases
      of rebound compartmental syndromes after unilateral fasciotomy reveal the skin as
      an important limiting factor in severe cases of compartmental syndrome.

PMID- 7821080
TI  - [Can unreamed tibial nailing replace external fixators in management of open
      tibial fractures?].
AB  - The recently developed unreamed tibial nail (UTN) offers a new possibility for
      biological osteosynthesis by intramedullary stabilization for tibial fractures
      including those with severe closed and open soft tissue damage. In a
      retrospective study we compared the well established method of external fixation
      with unreamed intramedullary nailing for open tibial shaft fractures. The data of
      our first 15 cases treated primarily by UTN (Group 1) and another 15 cases
      comparable in etiology, severity of trauma, fracture classification, open soft
      tissue damage and the rate for myocutaneous flaps and skin-grafts, treated
      initially by external fixation (Group 2) were reviewed. Septic complications were
      only seen in group 2 and made necessary a lot of following additional operations.
      One angular deformity was seen in each group. Group 1 showed a mean hospital stay
      of 26.3 days compared to 75.7 days in group 2. Full weight-bearing was achieved
      after 1.8 months (group 1) whereas it took 4.5 months in group 2. The first
      clinical experience using the UTN shows an obvious advantage in comparison to
      fracture management by external fixation mainly due to a low complication rate
      and a much shorter over all surgical treatment period.

PMID- 7821082
TI  - [Long-term results of replacement of the anterior cruciate ligament in comparison
      with conservative therapy].
AB  - Between January 1980 and February 1987 92 patients (group I) with chronic
      anterior instability of the knee joint underwent anterior cruciate ligament
      reconstruction using midthird patellar tendon autografts (BTB). 39 patients
      (group II) with the same injury were treated conservatively. The patients were
      followed up postoperatively within a mean period of 8.5 years and stability,
      grade of postoperative arthrosis, subjective view of patients and ability to
      sport were evaluated. In group I the clinical examination showed in 77% the same
      stability on both sides, whereas in group II no cases of bilateral stability of
      same grade were found. Pivot shifting was repaired in 91% of group I and only in
      17% of group II patients. The apparative examination of the stability (KT 2000
      arthrometer testing) measuring the anterior drawer phenomenon on both knees
      showed stable joint conditions (anterior tibia displacement < or = 3 mm) in 86%
      of operatively treated and only in 8% of conservatively treated patients.
      Postoperative x-rays showed no arthrotic changes in 55% of group I patients. All
      patients of group II showed signs of progredient arthrosis in their postoperative
      x-rays. Subjective clinical results were good to excellent in all group I
      patients. Only 50% in group II had a good to excellent result. 67% of group I and
      only 25% of group II patients practiced their former sports activities again. In
      our retrospective review we could observe significant better clinical results of
      surgically treated old isolated anterior cruciate ligament (ACL) tears with
      patellar tendon autografts (BTB) compared to those with conservative treatment.

PMID- 7821083
TI  - [Surgical treatment of fractures of the distal radius--a closed therapy concept.
      Initial results with the bowl osteosynthesis].
AB  - We present our treatment strategy for distal radius fractures, based on
      intrafocal pinning (Kapandji) and further combination with a palmar plate
      resulting in bowl osteosynthesis (Nonnenmacher). Even with a changing surgical
      team, we got more than 80% good results and rapid revalidation. We thus favor
      dynamic minimal osteosynthesis close to the fracture physiopathology. Indication
      for external fixation becomes limited to open or comminutive fractures.

PMID- 7821085
TI  - Modeling the 3-D RNA distribution in the Balbiani ring granule.
AB  - Mature Balbiani Ring (BR) granules in situ were stained with the nucleic acid
      specific stain, osmium ammine-B, recorded by electron spectroscopic imaging and
      reconstructed by electron microscope tomography to examine the three-dimensional
      (3-D) distribution of BR heterogeneous nuclear RNA (hnRNA). The BR2 granules
      contain ca. 37 kb of mRNA. Reconstructed BR granules were selected to emphasize
      one of the prevalent conformations seen in the sectioned salivary glands, the en
      face or "pin-wheel" conformation. A variety of image processing and volume
      rendering operations were applied to the set of reconstructed BR granules. Some
      of the conclusions of this study are the following: (1) RNA distribution is not
      uniform throughout the granule; (2) RNA is condensed into about ten particles per
      granule, which all appear to possess approximately the same RNA stain density;
      (3) heterogeneity exists in the positions and sizes of particles within the
      various BR granules. These data argue for the folding of a beaded ribbon,
      consisting of connected particulate condensations of BR mRNA, possessing
      considerable 3-D flexibility, even in the packaged state. A comparison of this
      beaded-ribbon model and a prior folded hnRNP fiber model is also presented.

PMID- 7821084
TI  - Stably DNA-bound chromosomal proteins.
AB  - DNA accomplishes its biological function in a complex with nuclear proteins. A
      minor protein fraction has been found in chromatin which could not be dissociated
      from DNA by reagents abolishing non-covalent type of interactions. The
      controversy surrounding the nature of the protein moiety and the nature of the
      bond linking the two components on the one hand, and the fact pointing to its
      evolutionary conservatism and metabolic stability on the other, make it necessary
      to critically evaluate the data in view of the possible biological function for
      such proteins.

PMID- 7821086
TI  - A defective non-LTR retrotransposon is dispersed throughout the genome of the
      silkworm, Bombyx mori.
AB  - The presence of long repetitive sequences is demonstrated in the genome of the
      silkworm, Bombyx mori. Members of this BMC1 family reveal several features
      typical of the L1 (long interspersed sequence one) family of mammals, except for
      species specific elements. The number of BMC1 elements is estimated to be
      approximately 3500 per haploid genome. Elements containing the full length unit
      of 5.1 kb are dispersed throughout the genome and their restriction sites are
      conserved, although most members are preferentially truncated to varying extents
      at their 5' ends. DNA sequencing indicates that this element contains six tandem
      repeats of 15 bp CpG-rich sequence in the 5' proximal region. It terminates with
      a 3' oligo(A) stretch, and is flanked at both ends by a 7-10 bp target sequence
      duplication. In addition, there is significant evidence for amino acid sequence
      homology with reverse transcriptase domains of other L1 families, especially F,
      Doc and Jockey of Drosophila melanogaster. No large open reading frame is
      present. The BMC1 element is suggested to be dispersed in the genome by a
      transposition mechanism involving RNA intermediates.

PMID- 7821087
TI  - Interstitial deletions of repetitive DNA blocks in dicentric human Y chromosomes.
AB  - Cytogenetic analysis of aberrant human Y chromosomes was done by fluorescence in
      situ hybridization (FISH) with Y specific repetitive DNA probes. It revealed an
      interstitial deletion of different DNA blocks in two dicentric chromosome
      structures. One deletion includes the total alphoid DNA structure of one
      centromeric region. The second deletion includes the total repetitive DYZ5 DNA
      structure in the pericentromeric region of one short Y arm. Both dicentric Y
      chromosomes were iso(Yp) chromosomes with break and fusion point located in Yq11,
      the euchromatic part of the long Y arm. Their phenotypic appearance was
      "abnormal", resembling small monocentric Yq-chromosomes in metaphase plates.
      Mosaic cell lines, usually included in karyotypes with dicentric Y chromosomes,
      were not observed. It is assumed that both deletion events suppress the
      kinetochore activity in one Y centromeric region and thus stabilize its dicentric
      structure. Local interstitial deletion events had not been described in dicentric
      human Y chromosomes, but are common in dicentric yeast chromosomes. This raises
      the question of whether deletion events in dicentric human chromosomes are rare
      or restricted to the Y chromosome or also represent a general possibility for
      stabilization of a dicentric chromosome structure in human.

PMID- 7821089
TI  - Chemical induction of quadruple and octuple chromosomes in Chinese hamster CHO-K1
      cells and relationship between their three-dimensional structure and spatial
      distribution of BrdU-labeled chromatids.
AB  - Double endoreduplication of Chinese hamster CHO-K1 cells that exhibited quadruple
      chromosomes at metaphase was induced by a combination of rotenone and ammonium
      vanadate treatments. Analysis of sister chromatid differential staining patterns
      (using 5-bromo-2'-deoxyuridine) revealed that approximately 50% of the quadruple
      chromosomes did not keep the scheme of "outside replication" of DNA. Based on the
      ratio of the staining patterns observed, we suggest that the two diplochromosomes
      forming a quadruple chromosome are held together by a physical link connecting
      the two original chromatids. Metaphases with octuple chromosomes were also
      produced by the same treatment. Each chromosome constituting an octuple
      chromosome was longer and thinner than ordinary metaphase chromosomes. This
      suggests incomplete chromosome condensation at metaphase. The majority of octuple
      chromosomes showed the eight constituent chromosomes to be so enmeshed that a
      planar alignment could not be observed in air-dried preparations.

PMID- 7821088
TI  - Physical mapping of 5S rDNA reveals a new locus on 3R and unexpected complexity
      in a rye translocation used in chromosome mapping.
AB  - Using fluorescence in situ hybridization (FISH) with probe pScT7, three different
      5S rDNA loci were detected in the satellite of rye chromosome 1R (5SDna-R1) and
      in the short arms of chromosomes 3R (5SDna-R3) and 5R (5SDna-R2) respectively.
      All three loci showed polymorphism for the hybridization signal intensity. In
      order to determine the localization of these rye 5S rDNA multigene loci with
      higher precision within the corresponding chromosome arms, the probe pScT7 was
      physically mapped by FISH in relation to the following five translocations
      (Wageningen Tester Set): T850W (1RS/4RL), T248W (1RS/6RS), T273W (1RS/5RL), T305W
      (2RS/5RS) and T240W (3RS/5RL). Accurate physical maps of the translocation
      breakpoints had previously been made using electron microscope analysis of spread
      pachytene synaptonemal complexes of heterozygotes for the different
      translocations. The results indicate that locus 5SDna-R3 is located between the
      breakpoint of translocation T240W and the telomere, whereas locus 5SDna-R2 is
      located between the breakpoint of translocation T305W and the centromere, the
      hybridization of probe pScT7 on T305W translocated chromosomes demonstrating the
      complex nature of this translocation. On the other hand, the simultaneous
      detection of probes pScT7 and pTA71 (18S-5.8S-26S rDNA) with two different
      fluorochromes, indicated that the breakpoints of translocations T850W and T248W
      are located between loci Nor-R1 and 5SDna-R1.

PMID- 7821090
TI  - Cell cycle dependent distribution of a centrosomal antigen at the perinuclear
      MTOC or at the kinetochores of higher plant cells.
AB  - Compelling evidence has been obtained in favour of the idea that the nuclear
      surface of higher plant cells is a microtubule-nucleating and/or organizing site
      (MTOC), in the absence of defined centrosomes. How these plant MTOC proteins are
      redistributed and function during the progression of the cell cycle remains
      entirely unknown. Using a monoclonal antibody (mAb 6C6) raised against isolated
      calf thymus centrosomes and showing apparent reaction with the plant nuclear
      surface, we followed the targeted antigen distribution during mitosis and meiosis
      of higher plants. Immunoblot analysis of protein fractions from Allium root
      meristematic cell extracts probed with mAb 6C6 reveals a polypeptide of an
      apparent Mr of 78000. In calf centrosome extracts, a polypeptide of comparable
      molecular mass is found in addition to a major antigen of Mr 180000 after mAb 6C6
      immunoblotting. During mitotic initiation, the plant antigen is prominent on the
      periphery of the prophase nucleus. When the nuclear envelope breaks down, the
      antigen suddenly becomes associated with the centromere-kinetochores until late
      anaphase. In telophase, when the nuclear envelope is being reconstructed, it is
      no longer detected at the kinetochores but is solely associated again with the
      nuclear surface. This antigen displays a unique spatial and temporal
      distribution, which may reflect the pathway of plant protein(s) between the
      nuclear surface and the kinetochores under cell cycle control. So far, such
      processes have not been described in higher plant cells. These observations shed
      light on the putative activity of the plant kinetochore as a protein
      transporter.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7821091
TI  - Meiosis in Drosophila males. I. The question of separate conjunctive mechanisms
      for the XY and autosomal bivalents.
AB  - The conjunctive mechanism of the XY bivalent is believed to differ from that of
      the autosomal bivalents in the achiasmate Drosophila melanogaster male. It has
      been proposed that hypothetical cohesive elements, termed collochores, hold the X
      and Y chromosomes together at or near their nucleolar organizing regions (NORs)
      and that collochores are not exhibited by autosomal bivalents. In electron
      micrographs, unique fibrillar material is observed between the X and Y
      chromosomes at the synaptic site. Recently, the 240 bp nontranscribed spacer
      associated with rRNA genes at the NOR has been implicated as the essential DNA
      sequence for XY pairing. To test whether this DNA sequence is always associated
      with XY pairing and to determine its relationship to the unique fibrillar
      material, we studied the XY bivalent in Drosophila simulans. The D. simulans Y
      chromosome has few, if any, rRNA genes, but does have a large block (3,000 kb or
      12,500 copies) of the nontranscribed spacer repeat located at the distal end of
      its long arm. This is in contrast to the D. melanogaster Y, which has the repeat
      located among rRNA genes on its short arm. Using light and electron microscopy,
      we show that the X does indeed pair with the distal end of the long arm of the D.
      simulans Y. However, no fibrillar material is evident in serial thin sections of
      the D. simulans XY bivalent, suggesting that this material (in D. melanogaster)
      may be remnants of the NOR rather than a morphological manifestation of the
      hypothetical collochores.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7821092
TI  - A monoclonal antibody to lateral element proteins in synaptonemal complexes of
      Lilium longiflorum.
AB  - To identify synaptonemal complex (SC) proteins in Lilium longiflorum (lily),
      monoclonal antibodies were generated using mice immunized with isolated pachytene
      nuclei. While most of the resulting monoclonal antibodies recognized nucleolar or
      chromatin proteins, one monoclonal antibody (anti-LE) was found that binds to
      lateral elements. Anti-LE bound more to lateral elements of SCs digested with
      DNase than to lateral elements that had not been digested with DNase. The
      opposite pattern of labeling was observed using monoclonal antibodies to lily
      chromatin and nucleolar proteins. These results indicate that anti-LE is
      specifically recognizing lateral element proteins and not chromatin or nucleolar
      proteins surrounding the lateral elements. On immunoblots, anti-LE binds to three
      pachytene nuclear proteins (Mr 60000, 66000 and 70000), two tetrad (early
      microspore) nuclear proteins (Mr 60000 and 70000), and two root tip nuclear
      proteins (Mr 52000 and 60000). However, anti-LE does not bind to proteins from
      leaf nuclei. Of these four tissues, leaf is the only one that does not have
      actively dividing cells. This observation suggests that at least some SC proteins
      are related to nuclear proteins from mitotically active cells.

PMID- 7821093
TI  - Nucleotide sequence analysis of precore and proximal core regions in patients
      with chronic hepatitis B treated with interferon.
AB  - The aim of the study was to estimate the prevalence of HBeAg defective mutants
      among patients with chronic hepatitis B (CHB) in the United States and to study
      the effect of interferon-alpha (IFN-alpha) on determining the occurrence of
      mutations in the HBV precore and proximal core regions. Twenty CHB patients who
      were treated with IFN-alpha were studied. Initially, all were HBV DNA positive by
      dot-blot hybridization; 17/20 were HBeAg positive, and 3/20 were anti-HBe
      positive. The precore (87 nt) and proximal core (81 nt) regions were sequenced
      after PCR amplification by the dideoxy chain termination method. In pretreatment
      sera, 15/20 patients harbored wild-type HBV only, while in 5/20 at least one
      nucleotide substitution was found. Mutations that prevent HBeAg synthesis were
      found in three patients, all of whom had G-to-A substitution at nt 1896 and two
      of them were anti-HBe positive. Follow-up sera were available in 18 patients.
      With respect to pretreatment specimen, 15/18 patients had no changes in the
      sequenced regions after therapy. Sequence changes were observed in the remaining
      three patients: In one an HBeAg defective strain was replaced by a wild-type
      strain; in the second a wild-type strain was replaced by an HBeAg defective
      strain; and in the third two mutations changing the deduced amino acid sequence
      of the core protein developed in the wild-type strain. In conclusion, most of our
      patients (85%) were initially infected by HBV strains having no mutations that
      prevented HBeAg synthesis. IFN-alpha therapy infrequently resulted in the
      appearance of mutations in the precore and proximal core regions.

PMID- 7821095
TI  - Adenocarcinoma of the ileum in a patient with cystic fibrosis.

PMID- 7821094
TI  - Carcinomas of the colon with multidirectional differentiation. Report of two
      cases and review of the literature.
AB  - Two cases of colonic carcinomas with multidirectional differentiation are
      presented. Both tumors showed light microscopic and immunohistochemical evidence
      of areas of adenocarcinomatous, squamous cell carcinomatous, and neuroendocrine
      differentiation. Only six similar cases have been previously reported. These
      highly malignant tumors support the recent concept of a multipotential stem cell
      within the mucosa of the gastrointestinal tract capable of differentiation in
      several directions.

PMID- 7821096
TI  - Determination of Helicobacter pylori status by reverse transcription-polymerase
      chain reaction. Comparison with urea breath test.
AB  - We previously reported the development and the possible application of reverse
      transcription-polymerase chain reaction (RT-PCR) assay for the detection of H.
      pylori in gastric mucosal biopsy specimens. In this communication, the
      application of this assay was assessed by comparing its results from 79 gastric
      biopsy specimens obtained from 68 patients with the more traditional [13C]urea
      breath test. When the amplified products were examined, the specificity and
      sensitivity of this RT-PCR assay were 100% and 47% on agarose gels and 80% and
      91% by Southern hybridization, respectively. The specificity and sensitivity of
      urea breath test were 91% and 96% and were generally superior to RT-PCR (negative
      predictive value of 94% for UBT and 59-76% for RT-PCR). Although our RT-PCR
      results compare favorably with other PCR assays applied to gastric biopsy
      specimens for the detection of H. pylori, the use of this method did not add
      significantly to currently available noninvasive diagnostic methods.

PMID- 7821097
TI  - Long-term prospective study of Helicobacter pylori in nonulcer dyspepsia.
AB  - Helicobacter pylori is present in up to 87% of patients with nonulcer dyspepsia.
      This study assessed the effect of eradicating Helicobacter pylori infection on
      the symptoms of nonulcer dyspepsia at four weeks and one year after treatment.
      Dyspepsia was assessed on the frequency and severity of six symptoms [epigastric
      pain (night and day), nausea and vomiting, upper abdominal discomfort, and
      regurgitation] where each symptom was scored from 0 to 4. Helicobacter pylori
      status was assessed before treatment and four weeks after treatment with
      histology and microbiology, and at one year with a carbon-13 urea breath test.
      Eighty-three patients (23 males, 60 females; mean age 56.3 years; mean symptom
      duration 3.6 months) with nonulcer dyspepsia and Helicobacter pylori infection
      entered the study. Seventy-five were available at one year follow-up. Four weeks
      after treatment, the mean symptom score improved in those with eradication (6.95
      2.3, P = 0.01, N = 41) or persistent infection (6.69-3.0, P = 0.015, N = 42). At
      one year, those with persistent Helicobacter pylori infection (N = 38, score
      5.24) had a higher score than those remaining clear of infection (N = 24, score
      1.4, P < 0.0001) and those with reinfection (N = 13, score 2.2, P < 0.0001). In
      addition, persistent Helicobacter pylori infection was associated with more
      additional treatments than those with eradication (34/38 versus 4/37, P < 0.001).
      These results suggest that Helicobacter pylori plays an important role in the
      symptoms of nonulcer dyspepsia.

PMID- 7821098
TI  - Gastric mucosal high-energy phosphate metabolism. Influence of ethanol and PGE2.
AB  - This study investigated potential alterations in gastric mucosal energy
      metabolism following exposure to the damaging agent 50% ethanol (50% EtOH) alone
      and after pretreatment with either 16,16-dimethyl (dmPGE2) or the mild irritant
      25% ethanol (25% EtOH). Fasted rats (n = 12-26/group) were orally given 1 ml of
      normal saline (NS), dmPGE2 in a dose of 5 micrograms/kg, or 25% EtOH. Fifteen
      minutes later, they randomly received 1 ml of NS or 50% EtOH. After 5 min, rats
      were anesthetized and their stomachs rapidly excised, frozen in liquid nitrogen,
      and lyophyllized. Once dried, the surface area (in square millimeters) of mucosal
      lesions was quantitated. Mucosa was then scraped off the underlying muscularis.
      Tissue metabolites (ATP, ADP, AMP, lactate, pyruvate, glucose, and glucose-6
      phosphate) were measured in deproteinized, neutralized samples by enzymatic
      methods. In conjunction with the development of mucosal lesions involving an
      average of 45 mm2, ATP was significantly (P < 0.05) lower and AMP significantly
      higher in 50% EtOH-treated animals (indicating dephosphorylation) when compared
      with NS controls. Although both 25% EtOH and dmPGE2 prevented these lesions, only
      25% EtOH prevented the ATP and AMP alterations. Fifty percent EtOH also
      significantly increased the tissue content of glucose and lactate over control
      values while glucose-6-phosphate was significantly decreased. With both
      protective agents pyruvate levels were significantly reduced, while glucose and
      lactate levels were not affected. In contrast to dmPGE2, the mild irritant (25%
      EtOH) significantly increased glucose-6-phosphate levels over control.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7821099
TI  - Abnormalities in the shape of the duodenal loop on X-ray. Associated with
      idiopathic antral hypomotility?
AB  - We aimed to determine if abnormalities in the shape of the duodenal loop would be
      useful in identifying patients with gastroduodenal dysmotility. Retrospectively,
      126 consecutive patients with suspected functional abdominal symptoms who
      underwent upper gastrointestinal barium x-ray studies and gastrointestinal
      manometry were independently evaluated. Twenty-seven patients (21%) had an
      abnormally shaped duodenal loop (two proximal and 25 distal) by x-ray. An
      abnormal duodenal loop was associated with female gender but the presenting
      symptoms were similar in patients with normal and abnormal loops. Antral
      hypomotility was significantly more common in patients with distal duodenal
      malrotations compared to those with a normal x-ray (56% vs 27%, P < 0.01);
      intestinal dysmotility was not associated with the shape of the duodenal loop.
      The presence of an abnormally shaped duodenal loop in patients presenting with
      functional gastrointestinal symptoms may be a useful marker for idiopathic antral
      hypomotility.

PMID- 7821100
TI  - Effects of nonsteroidal antiinflammatory drugs on ulcerogenesis and gastric
      secretion in pylorus-ligated rat.
AB  - The effects of nonsteroidal antiinflammatory drugs on ulcerogenesis and gastric
      secretion were evaluated in a pylorus-ligated rat model. Oral administration of
      salicylate (50 mg/kg), aspirin (50 mg/kg), and indomethacin (3.5 mg/kg)
      significantly increased ulcerogenesis over the basal value by six- to sevenfold,
      but ibuprofen's (10 mg/kg) fourfold increase was not significant. Aspirin in
      conjunction with histamine (0.5 mg/kg subcutaneously) significantly increased
      ulcerogenesis by 2.7-fold compared to histamine alone. Basal acid secretion was
      increased significantly by 156% after indomethacin, but not by other nonsteroidal
      antiinflammatory drugs. In contrast, all nonsteroidal antiinflammatory drugs,
      except indomethacin, significantly decreased histamine-stimulated acid secretion.
      Non-steroidal antiinflammatory drugs had no effect on pepsinogen secretion.
      Ranitidine pretreatment (25 mg/kg intraperitoneally) significantly decreased
      basal acid and pepsinogen secretion in all treatment groups by > 85% and > 40%,
      respectively, and ulcerations induced by salicylate, aspirin, and indomethacin
      were also inhibited by 90%, 60%, and 60%, respectively. The observed inhibition
      of prostaglandin E2 generation by nonsteroidal antiinflammatory drugs under basal
      secretory conditions appeared to correlate with the extent of ulcerogenesis. Our
      data support the concept that acid, in addition to inhibition of prostaglandin E2
      synthesis, plays an important role in the pathogenesis of nonsteroidal
      antiinflammatory drug-induced gastropathy.

PMID- 7821101
TI  - Serial assay of hepatitis C virus RNA in serum for predicting response to
      interferon-alpha therapy.
AB  - To determine whether the loss of serum hepatitis C virus RNA (HCV-RNA) early in
      interferon therapy would indicate a sustained response to this agent, we detected
      serum HCV-RNA successively during and after therapy. Serum samples for detection
      of HCV-RNA were obtained serially from 36 patients with chronic hepatitis C
      treated with interferon-alpha. In 28 of these patients, results of the assay were
      compared with genotypes and quantitative levels of HCV-RNA in serum before
      therapy. HCV-RNA was detected by a reverse transcription polymerase chain
      reaction using the 5'-noncoding region as a primer. Genotypes were determined by
      using type-specific primers, and serum levels of HCV-RNA were determined by a
      competitive reverse transcription polymerase chain reaction (RT-PCR). HCV-RNA
      disappeared from serum in eight of 10 responders (80%), but in only one of the 26
      nonresponders (3.8%) at the second week of therapy (P < 0.0005). The time until
      the disappearance of HCV-RNA was correlated with the serum level of HCV-RNA
      present before therapy (P < 0.05). The early disappearance of HCV-RNA from serum
      during interferon therapy was useful in predicting a sustained response in
      patients with chronic hepatitis C.

PMID- 7821102
TI  - Gastric emptying response to variable oral erythromycin dosing in diabetic
      gastroparesis.
AB  - Intravenous erythromycin has been shown to improve gastric emptying in diabetic
      gastroparesis. Oral erythromycin also accelerates gastric emptying, but to a
      lesser degree. To determine if this is a dose-dependent phenomenon, gastric
      emptying was measured in 10 insulin-requiring diabetic patients with
      gastroparesis after administration of either 250 mg or 1000 mg of erythromycin or
      placebo. The drugs were orally administered in a randomized, double-blind fashion
      30 min prior to ingestion of a meal containing [99mTc]-sulfur colloid-labeled
      beef stew and [111In]DTPA-labeled orange juice. Anterior and posterior gastric
      images were recorded for 3 hr at 15-min intervals using an externally positioned
      gamma camera. The results demonstrated that both doses of oral erythromycin
      significantly improved solid-phase gastric emptying. The mean half-emptying time
      of solids was decreased from 151 +/- 40 min with placebo to 58 +/- 10 min and 40
      +/- 9 min with 250 mg and 1000 mg of erythromycin, respectively. However, a dose
      dependent relationship was not demonstrated with the two doses of erythromycin
      employed. These results suggest that for most patients with diabetic
      gastroparesis, a single 250-mg dose of erythromycin will significantly improve
      gastric emptying. It is possible that a dose-dependent relationship will be
      demonstrated with doses of erythromycin less than 250 mg.

PMID- 7821103
TI  - Helicobacter pylori infection. A reversible cause of hypergastrinemia and
      hyperchlorhydria which may mimic Zollinger-Ellison syndrome.
AB  - The present report describes two patients with fasting hypergastrinemia, gastric
      acid hypersecretion, and Helicobacter pylori gastritis. Provocative testing for
      Zollinger-Ellison syndrome was negative and imaging studies did not demonstrate
      an intra-abdominal mass. Following eradication of the Helicobacter pylori
      infection, the fasting hypergastrinemia resolved in both patients and in one
      patient the gastric acid hypersecretion also resolved. The implications of this
      case on the differential diagnosis of Zollinger-Ellison syndrome are discussed.

PMID- 7821104
TI  - Effect of plaunotol on hypergastrinemia induced by long-term omeprazole
      administration in humans.
AB  - Omeprazole markedly inhibits basal and stimulated gastric acid secretion and has
      the ability to produce hypergastrinemia and hyperplasia of enterochromaffin-like
      cells in humans. On the other hand, plaunotol, an acyclic diterpene alcohol, has
      been reported to inhibit gastrin release by stimulating endogenous secretion
      release. We investigated the effect of plaunotol on serum gastrin levels after
      six to eight weeks of omeprazole (20 mg/day) administration in 22 patients (16
      males, 6 females; mean age 52.3, range 36-70 years) with peptic ulcer disease.
      The patients were randomized to the following two groups: 11 subjects with
      omerprazole alone (single group) and 11 with omeprazole plus plaunotol (240
      mg/day) (combination group) treatment. There were no significant differences
      between the two groups concerning age, sex, ulcer stage, ulcer history,
      environmental factors, and Helicobacter pylori (HP) prevalence. After complete
      drug(s) administration, serum immunoreactive (ir) -gastrin levels increased
      significantly in the single group (P < 0.001) in contrast to the combination
      group, and plaunotol significantly inhibited hypergastrinemia induced by
      omeprazole administration (P < 0.001). Significant increases in serum ir
      calcitonin gene-related peptide concentrations were observed in the combination
      group compared to the single group (P < 0.05). However, there were no significant
      changes in sereum ir-secretin, somatostatin, and vasoactive intestinal
      polypeptide levels as well as ulcer healing and HP prevalence between the two
      groups. These findings suggest that plaunotol may suppress hypergastrinemia
      induced by long-term omeprazole administration, at least partly, via a certain
      brain-gut hormone affecting gastrin release.

PMID- 7821105
TI  - Endoscopic, radiographic, and manometric findings associated with cardiovascular
      dysphagia.
AB  - The roentgenographic, echocardiographic, endoscopic, and manometric findings were
      studied in five consecutive patients with cardiovascular dysphagia, including
      four with a dilated left atrium and one with an anomalous left subclavian artery.
      Common and different manometric findings were found in the two types of
      cardiovascular dysphagia. The major manometric abnormality in all cases was an
      elevated baseline pressure, with superimposed large rhythmic pressure waves
      occurring at the same frequency as the electrocardiogram in the mid-esophagus.
      This manometric abnormality, produced by pulsatile cardiovascular compression,
      provides direct evidence that cardiovascular dysphagia is caused by esophageal
      luminal obstruction from cardiovascular compression. Indirect evidence supporting
      this mechanism includes smooth extrinsic compression and hang-up of ingested
      barium in the mid-esophagus on esophagogram and transmitted mural pulsations and
      a compressed lumen in the mid-esophagus at panendoscopy. Two of the five patients
      had deranged esophageal peristalsis within the high-pressure zone, which also
      contributed to the dysphagia. Autopsy in one patient with deranged peristalsis
      revealed a band of ischemic esophageal mucosa in the zone compressed by the
      dilated left atrium. A novel manometric maneuver might distinguish dysphagia due
      to an anomalous left subclavian artery from dysphagia due to a dilated left
      atrium. Left arm elevation during manometry in the single patient with the
      anomalous artery significantly increased the mean mid-esophageal baseline
      pressure by 92% (N = 10 trials), and mean pressure wave amplitude by 93% (N = 10
      trials, P < 0.002 for each, nonparametric signed rank test). Left arm elevation
      in this patient also increased the observed luminal obstruction during endoscopy.
      These manometric and endoscopic findings may be explained by increased arterial
      compression of the esophagus produced by arterial stretch and anterior
      displacement with arm elevation.

PMID- 7821106
TI  - Effect of isosorbide dinitrate on gastroesophageal reflux in healthy volunteers
      and patients with Chagas' disease.
AB  - The effect of isosorbide dinitrate (ISD) on gastroesophageal reflux and gastric
      emptying during the 24-min period following a liquid meal was studied in healthy
      volunteers, Chagas' disease patients with normal esophageal motility (CD-1
      group), and Chagas' disease patients with esophageal dysmotility (CD-2 group)
      with dynamic scintigraphy. At random, on two separate days, the subjects received
      5 mg isosorbide dinitrate or an identical-appearing placebo tablet, by the
      sublingual route, and ingested a liquid test meal containing [99mTc]phytate
      colloid before scintigraphic studies were performed. Gastroesophageal reflux
      episodes were more frequent (P = 0.016) and gastroesophageal reflux indexes were
      greater (P < 0.010) after isosorbide dinitrate than after placebo in CD-2 group
      (N = 15) but not in healthy volunteers (N = 14) or CD-1 group (N = 9); six of
      seven CD-2 patients presenting with gastroesophageal reflux after isosorbide
      dinitrate had abnormal clearance of refluxate. Gastric emptying was similar in
      healthy volunteers (N = 13), CD-1 patients (N = 6), and CD-2 patients (N = 13),
      and no effect of isosorbide dinitrate on it was detected in any of the groups. In
      separate studies, 5 mg isosorbide dinitrate reduced the lower esophageal pressure
      (P < 0.01) in seven CD-2 patients. These results indicate that ISD increases the
      tendency towards GER in CD-2 patients, but not in healthy volunteers or CD-1
      patients. This effect is probably related to an exceedingly intense relaxation of
      the LES caused by ISD in CD-2 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7821107
TI  - Bacterial esophagitis associated with CD4+ T-lymphocytopenia without HIV
      infection. Possible role of corticosteroid treatment.
AB  - Although infectious esophagitis is usually due to infection with Candida, herpes
      virus, or cytomegalovirus, bacterial esophagitis is occasionally observed.
      Recently, patients have been reported with CD4+ T-lymphocytopenia without HIV
      infection. Bacterial esophagitis per se has not been reported in these patients.
      We report the case of an 80-year-old patient admitted with a COPD exacerbation
      after being on chronic steroids. The patient developed esophageal symptoms and
      was found to have bacterial esophagitis by biopsy. Her CD4+ counts were found to
      be low, but she denied HIV risk factors and HIV testing was negative. Her CD4+
      counts rose into the normal range as her steroids were tapered, and her
      esophagitis improved on antibiotics. This case is reported to alert physicians to
      the possible association of bacterial esophagitis with CD4+ T-lymphocytopenia
      without HIV infection and to discuss the possible etiological role of
      corticosteroid treatment.

PMID- 7821108
TI  - Cryptosporidium gastropathy. Presentation of a case and review of the literature.

PMID- 7821109
TI  - Acid-suppression did not enhance healing of gastric ulcer associated with
      paraesophageal hernia after hernial reduction.

PMID- 7821110
TI  - Alterations in rat peripheral blood neutrophil function as a consequence of
      colitis.
AB  - Altered peripheral neutrophil function is a feature of IBD that may contribute to
      the chronicity and extragastrointestinal manifestations of this disease, but
      clinical evidence for such alterations is confounded by variations in patient
      characteristics, disease onset, and use of therapeutics that can influence
      neutrophil function. The use of a rat model of colitis has permitted us to
      characterize, in a controlled manner, the causal relationship between colitis and
      altered peripheral neutrophil function. At various times after induction of
      colitis with trinitrobenzene sulfonic acid (TNBS), peripheral neutrophils were
      isolated and assays of phagocytosis, chemotaxis, leukotriene B4 (LTB4) synthesis,
      and superoxide production were performed using a variety of stimuli. Circulating
      neutrophil numbers increased about fourfold within 12 hr of TNBS administration
      and returned to normal levels over the following two weeks. LTB4 synthesis in
      response to calcium ionophore decreased at 12 hr after induction of colitis, then
      returned to control levels. The chemotactic responses of peripheral neutrophils
      to LTB4 and FMLP in vitro and to LTB4 and IL-8 in vivo were profoundly suppressed
      through the two-week study period. Phagocytosis of nitroblue tetrazolium was
      significantly enhanced (ca. threefold) at 12 hr after induction of colitis and
      remained elevated throughout the study period. Superoxide production was also
      significantly elevated in the early phase of colitis (by ca. fourfold), but was
      not different from control levels at seven and 14 days. These results demonstrate
      that colonic inflammation profoundly influences peripheral blood neutrophil
      function, although the direction and magnitude of the alteration varied among the
      various functions assessed. The prolonged depression of chemotactic activity may
      represent a physiological reaction to limit the inflammatory response.

PMID- 7821112
TI  - Serum carboxy terminal propeptide of type I procollagen to amino terminal
      propeptide of type III procollagen ratio is a better indicator than each single
      propeptide and 7S domain type IV collagen for progressive fibrogenesis in chronic
      viral liver diseases.
AB  - Twenty chronic viral hepatitis patients, mainly with hepatitis B related with
      progression to liver cirrhosis were included for an assay of serum collagen
      markers: PICP (carboxy terminal propeptide of type I procollagen), PIIINP (amino
      terminal propeptide of type III procollagen), and 7S-IV (7S-domain type IV
      collagen). PICP is increased in 20% of chronic hepatitis patients with a mean of
      190.3 ng/ml, which is not different from that of the follow-up concentration in
      liver cirrhosis, where 35% of cases were abnormal with a mean of 220.5 ng/ml. The
      serum level and percent of abnormality of PIIICP in chronic hepatitis and in
      liver cirrhosis are 23.5 ng/ml vs 14.8 ng/ml and 90% vs 100%, respectively (P >
      0.05). PICP/PIIINP is significantly higher during liver cirrhosis (15.11 vs
      10.08, P < 0.05). PICP during chronic hepatitis is not related to serum
      biochemical changes, while PICP during liver cirrhosis and PIIINP are correlated
      with hepatic enzymes. 7S-IV in chronic hepatitis and in liver cirrhosis is 14.0
      ng/ml vs 10.9 ng/ml, respectively; both were positively correlated with hepatic
      enzymes. These results suggest that PICP/PIIINP is a better indicator of hepatic
      fibrogenesis than either PICP or PIIINP alone in viral hepatitis. A ratio of more
      than 12 is suggestive of liver cirrhosis.

PMID- 7821111
TI  - Phenotypic and functional characterization of T-cell lines generated from
      colonoscopic biopsy specimens in patients with ulcerative colitis.
AB  - Intestinal T-cell lines were generated from lamina propria mononuclear cells
      isolated from colonoscopic biopsies in ulcerative colitis patients and controls.
      In both ulcerative colitis and controls, expanded cells were constituted largely
      by T-cell receptor alpha beta+, CD4+, CD45RA- (helper), and CD8+, CD11b-
      (cytotoxic) phenotypes. T-cell receptor V beta gene usage was not significantly
      changed after cell expansion and no difference was observed between ulcerative
      colitis and controls. Ulcerative colitis cells, especially those derived from the
      patients with long-standing disease, showed significantly higher levels of
      cytotoxicity against the target cells, including those of colonic epithelial
      origin, and enhanced production of tumor necrosis factor-alpha and interferon
      gamma after short incubation with anti-CD3 antibody. Generation of T-cell lines
      from colonoscopic biopsy specimens may be useful for detailed functional
      characterization of locally infiltrating T cells in ulcerative colitis patients.

PMID- 7821113
TI  - Effect of radiation and radioprotection on small intestinal function in canines.
AB  - Radiation with doses > 7.5 Gy damages the canine intestinal mucosa, and
      pretreatment with WR2721 reduces this damage. However, the effects of radiation
      and of WR2721 on in vivo intestinal transport are unclear. Therefore, we
      determined canine survival, intestinal transport, and mucosal histology following
      unilateral abdominal irradiation. Isoperistaltic ileostomies were prepared in 23
      dogs under general anesthesia and aseptic conditions. After a three-week recovery
      period, animals were given either placebo or WR2721, 150 mg/kg intravenously, 30
      min prior to 10 Gy cobalt-60 abdominal irradiation. Ileal transport and histology
      were determined in both groups before exposure and one, four, and seven days
      after irradiation. Seven-day survival was significantly improved by pretreatment
      with WR2721 (91% vs 33%, P < 0.02). On day 4, both mucosal integrity and net
      intestinal absorption were significantly better (P < 0.05) after WR2721 than
      after placebo. Thus, radiation-induced damage to the ileal mucosa is accompanied
      by a reduction in net ileal absorption of water and electrolytes in vivo. In
      addition, pretreatment with WR2721 improves animal survival while reducing ileal
      damage and improving intestinal absorption.

PMID- 7821114
TI  - Pseudo-Crohn's disease with bloody diarrhea. A case of Munchausen's syndrome.

PMID- 7821115
TI  - Virtue and physicians.

PMID- 7821116
TI  - Crigler-Najjar syndrome type II. New observation of possible autosomal recessive
      inheritance.
AB  - The inheritance of Crigler-Najjar syndrome type II (CNS II) is still unclear.
      Both autosomal dominant transmission with variable penetrance and autosomal
      recessive transmission have been reported. We describe the diagnosis of CNS II in
      an adult patient with unconjugated serum bilirubin levels up to 19.6 mg/dl and no
      detectable activity of bilirubin UDP-glucuronosyltransferase in the liver biopsy.
      Serum bilirubin levels decreased markedly on phenobarbital treatment. The parents
      of our patient are first cousins. The mother and three of the patient's five sibs
      were jaundiced within a few days of birth. Our patient and her jaundiced siblings
      have 11 children, all healthy and anicteric. We conclude from these data that the
      inheritance of this very rare disease follows an autosomal recessive pattern,
      with pseudodominance in this family.

PMID- 7821117
TI  - Use of prostaglandin I2 analog in treatment of massive hepatic necrosis
      associated with endothelial cell injury and diffuse sinusoidal fibrin deposition.
AB  - Endothelial cell damage causes massive hepatic necrosis as a result of fibrin
      deposition in the hepatic sinusoids. When a stable analog of prostaglandin I2,
      beraprost sodium, was administered to rats given either dimethylnitrosamine,
      carbon tetrachloride, or endotoxin following Corynebacterium parvum
      administration, the hepatic necrosis produced in each was attenuated, but to a
      greater extent in the dimethylnitrosamine and endotoxin/Corynebacterium parvum
      models, where fibrin deposition in the hepatic sinusoids occurs, as compared to
      the carbon tetrachloride model, where such fibrin deposition does not occur.
      Beraprost sodium reduced the expected increase of portal venous pressure in the
      endotoxin/Corynebacterium parvum model without affecting plasma thrombin
      antithrombin III complex levels. Beraprost sodium also significantly reduced cell
      killing of both isolated rat hepatocytes and hepatic sinusoidal endothelial cells
      exposed to tert-butyl hydroperoxide when compared to controls. Beraprost sodium
      could prove to be a therapeutic candidate for the treatment of hepatic necrosis,
      particularly in cases associated with fibrin deposition in the hepatic sinusoids
      because of its fibrin clot-clearing action.

PMID- 7821118
TI  - Effects of exercise-induced sympathoadrenergic activation on portal blood flow.
AB  - We examined the relationship between portal venous blood flow and
      sympathoadrenergic activation after muscle exercise. For this purpose, we used
      echo Doppler and measured plasma noradrenaline concentration before and after
      mild (7 metabolic units, N = 8) and maximal exercise (14 metabolic units, N = 8)
      in 16 patients without significant disease. Portal venous flow did not change
      after mild exercise. In contrast, a significant reduction in portal venous flow
      was observed after maximal exercise (P < 0.01). This was due to reductions in
      both cross-sectional area of the portal vein (P < 0.01) and portal venous
      velocity (P < 0.01). Overall, there were significant inverse relationships
      between the change in plasma noradrenaline concentration and that in cross
      sectional area of the portal vein [r = -0.44, P < 0.01 (absolute change); r = 
      0.47, P < 0.01 (relative change)], that in portal venous velocity (r = -0.63, P <
      0.01; r = -0.61, P < 0.01), and that in portal venous flow (r = -0.54, P < 0.01;
      r = -0.59, P < 0.01). These results suggest that the reduction in portal venous
      flow after exercise is related to the degree of sympathoadrenergic activation.
      This reduction may be due mainly to splanchnic vasoconstriction.

PMID- 7821119
TI  - Use of OKT3 monoclonal antibody as induction therapy for control of rejection in
      liver transplantation.
AB  - This report details a single center's experience with OKT3 induction
      immunosuppression for liver transplantation. One hundred ninety-nine consecutive,
      unselected adult liver recipients received OKT3 therapy for 9-10 days combined
      with low-dose steroids and azathioprine. Cyclosporine was begun to overlap with
      the last few days of OKT3 therapy. The average dose of OKT3 was 45 mg. Fifty-two
      patients (26.1%) experienced 57 episodes of acute rejection. The median time of
      onset of rejection was 18 days after grafting. Seventy-eight percent of the
      rejection episodes were steroid-sensitive. Recurrent rejection was uncommon and
      the need for OKT3 retreatment was infrequent. One year actuarial graft and
      patient survival was 79.7% and 82.3% respectively. Based on this evidence, it
      appears that OKT3 prophylaxis provides good control of acute rejection with a
      very low incidence of recurrent rejection.

PMID- 7821120
TI  - Immunomodulation of transplant rejection using monoclonal antibodies and soluble
      receptors.
AB  - The main objective of our studies has been to optimize the effects of monoclonal
      antibodies (MAbs) and other immunosuppressive reagents to enhance organ graft
      survival. One such agent is OKT3, a MAb that is directed against the CD3
      component of the human T-cell receptor (TCR) complex. Treatment of a rejection
      episode with OKT3 results in a rapid and efficient clearing of circulating T
      cells and reversal of most rejection episodes. Its wider use in transplantation
      and in the treatment of immune-mediated disease is limited by adverse reactions
      that follow the initial dose, the production of neutralizing Abs, and the
      transient nature of the immunosuppression. We have engineered CDR-grafted
      "humanized" anti-CD3 MAbs that lack Fc-receptor binding activity through
      mutagenesis of amino acids in the Fc portion of the MAb. This results in an
      immunosuppressive anti-CD3 MAb that is less antigenic and one that does not
      induce the first-dose side effects. In addition, we have pursued a goal of
      developing a therapy that will induce donor-specific tolerance while maintaining
      overall recipient immune competency. Because antigen-specific T-cell activation
      depends not only on TCR-ligand interaction, but also on additional costimulatory
      signals mediated by accessory molecules such as CD28, blocking the binding of
      CD28 on T cells to its ligand B7, during TCR engagement, might modulate
      transplantation responses. Using a soluble fusion protein of human CTLA4, CTLA4
      Ig, that binds B7 with high affinity, inhibition of human pancreatic islet
      rejection that occurs, at least in part, by affecting T-cell recognition of human
      B7+ antigen-presenting cells has been demonstrated.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7821121
TI  - Future of monoclonal antibodies in solid organ transplantation.
AB  - The ultimate objective of immunosuppressive therapy is to block transplant
      recipient reactivity to allograft incompatibilities while sparing other
      responses. Increased clarification of rejection mechanisms has made possible the
      precise suppression of specific elements of the immune response using murine anti
      human monoclonal antibodies. In addition, recombinant DNA technology has made
      available novel agents including "humanized," bispecific, or toxin-conjugated
      molecules, which avoid some of the limitations of murine reagents. Using such
      agents, donor-specific tolerance has been induced in experimental models after a
      limited course of therapy directed against selected effector cell surface
      associated molecules such as CD4, CD25, and CD54. It remains to be determined how
      such observations can be successfully transferred to the human situation. It
      seems likely, however, that as new molecular agents are developed, increasingly
      effective suppression of specific cellular targets will become an essential
      element of clinical protocols. Such agents may provide long-term
      immunosuppression with limited periods of immunosuppressive agent administration.

PMID- 7821122
TI  - Sphincter of Oddi dysfunction after liver transplantation.

PMID- 7821123
TI  - Listeria monocytogenes peritonitis.

PMID- 7821125
TI  - Resolution of nonsyndromic paucity of intrahepatic bile ducts in infancy.

PMID- 7821124
TI  - Effect of endogenous cholecystokinin on postprandial gallbladder refilling.
      Ultrasonographic study in healthy subjects and in gallstone patients.
AB  - The postprandial release of cholecystokinin (CCK) regulates gallbladder (GB)
      contraction but little is known about the role, if any, of the still-elevated CCK
      blood levels on subsequent GB refilling. To assess the role of CCK in GB
      refilling, a CCK-receptor antagonist, loxiglumide, or saline were infused
      intravenously in a random double-blind fashion after the ingestion of a liquid
      test meal in 16 healthy subjects. An identical study protocol was performed in 10
      GB "contractor" patient with radiolucent stones to ascertain whether the reported
      reduced CCK effect on GB emptying also affects GB refilling. GB volumes were
      assessed ultrasonographically in the fasting state and for 150 min at 15-min
      intervals after meal ingestion. GB volumes during postprandial refilling were
      significantly greater during loxiglumide than placebo infusion (P < 0.01), but
      they did not differ between gallstone and control subjects. In conclusion,
      postprandial endogenous CCK has a relevant role in delaying GB refilling, and
      this effect is not altered in patients with radiolucent gallstones.

PMID- 7821126
TI  - Effect of a tricyclic antidepressant on small intestinal motility in health and
      diarrhea-predominant irritable bowel syndrome.
AB  - Antidepressants are used in irritable bowel syndrome (IBS) and may have effects
      on the gut independent of improving mood. We have investigated the actions of a
      tricyclic antidepressant on small intestinal motor function in eight healthy
      volunteers and in six patients with diarrhea-predominant IBS. Fasting ambulatory
      motility was recorded from six small intestinal sites for 16-18 hr while on no
      drug (baseline) and while taking imipramine for five days. Orocecal transit time
      (OCTT) was measured by lactulose hydrogen breath test, during baseline and
      imipramine administration. Imipramine did not alter migrating motor complex
      periodicity, but slowed jejunal phase III propagation velocity in controls from
      7.5 +/- 1.1 to 3.6 +/- 0.5 cm/min (P < 0.01) and in IBS from 7.8 +/- 0.6 to 4.4
      +/- 0.5 cm/min (P < 0.0001). Phase III duration at each site was increased, and
      total recorded phase III was greater during imipramine than baseline studies.
      Imipramine increased the amplitude of phase III contractions. There was no effect
      of imipramine on non-phase-III motility index or discrete clustered contractions.
      Imipramine, prolonged OCTT from 73 +/- 6 min to 97 +/- 8 min in controls (P <
      0.05) and from 61 +/- 9 min to 89 +/- 8 min in IBS (P < 0.05). Although OCTT was
      shorter in the IBS group, no motility differences were seen between controls and
      IBS. This demonstration that a tricylic antidepressant can modify small
      intestinal motor function in health and in IBS supports the view that these drugs
      may have therapeutic actions in IBS unrelated to mood improvement.

PMID- 7821127
TI  - Effect of metformin on postprandial lipemia in patients with fairly to poorly
      controlled NIDDM.
AB  - OBJECTIVE: To quantify the effect of metformin on the metabolism of triglyceride
      (TG)-rich lipoprotein of intestinal origin in patients with non-insulin-dependent
      diabetes mellitus (NIDDM) who had responded to sulfonylurea but still had fasting
      hyperglycemia. RESEARCH DESIGN AND METHODS: Sixteen patients with NIDDM who had
      demonstrated a fall in fasting plasma glucose concentration > 2.2 mmol/l in
      response to glipizide treatment but continued to have fasting plasma glucose
      concentrations > 8.3 mmol/l were studied. Fasting glucose, GHb, lipid and
      lipoprotein concentrations were determined, and resistance to insulin-mediated
      glucose disposal was estimated by measuring the steady-state plasma glucose
      (SSPG) concentration at the end of a 180-min infusion of somatostatin, glucose,
      and insulin. In addition, plasma glucose, insulin, and TG concentrations were
      measured at frequent intervals from 0800 to 2400, with patients eating breakfast
      at 0800 and lunch at 1200. Vitamin A was also given at lunch, and the retinyl
      ester content in plasma and in chylomicron (Svedberg flotation constant [Sf] >
      400) and the chylomicron remnant (Sf 20-400) fractions were used to quantify the
      concentration of postprandial intestinal TG-rich lipoprotein from 1200 to 2400.
      RESULTS: Fasting plasma glucose concentrations (6.8 +/- 0.4 vs. 10.5 +/- 0.4
      mmol/l), GHb levels (7.9 +/- 0.3 vs. 10.8 +/- 0.5%), and day-long plasma glucose
      concentrations were all significantly lower after metformin treatment (P <
      0.001), which was associated with a significant (P < 0.001) fall in SSPG
      concentration (11.0 +/- 0.9 to 9.6 +/- 0.6 mmol/l). In addition, postprandial
      concentrations of glucose, insulin, free fatty acids, and TG were lower (P <
      0.001) following metformin treatment. Postprandial retinyl ester concentrations
      were also lower in plasma by 33 +/- 5.7% (P < 0.001) and in both the chylomicron
      (32 +/- 7.2%, P < 0.001) and chylomicron remnant (26 +/- 7.0%, P < 0.005)
      fractions. CONCLUSIONS: Addition of metformin to sulfonylurea-treated patients
      with NIDDM with less than optimal glycemic control was associated with improved
      glycemic control, lower postprandial insulin and TG concentrations, and a
      decrease in postprandial concentration of TG-rich lipoproteins of intestinal
      origin. All of these changes might be expected to decrease risk of coronary heart
      disease.

PMID- 7821128
TI  - Therapeutic comparison of metformin and sulfonylurea, alone and in various
      combinations. A double-blind controlled study.
AB  - OBJECTIVE: To assess and compare the therapeutic efficacy and safety of metformin
      (M) and sulfonylurea (glyburide, G), alone and in various combinations, in
      patients with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN
      AND METHODS: Of 165 patients (fasting blood glucose [FBG] > or = 6.7 mmol/l)
      initially treated with diet alone, 144 (FBG still > or = 6.7 mmol/l) were
      randomized to double-blind, double-dummy controlled treatment with M, G, or
      primary combination therapy (MG). The dose was titrated, with FBG < 6.7 mmol/l as
      target, using, at most, six dose levels. The first three dose levels comprised
      increasing single-drug therapy (M or G) or primary combination at increasing but
      low dosage (MGL), and the second three levels were composed of various high-dose
      combinations, i.e., add-on therapy (M/G or G/M) and primary combination escalated
      to high dosage (MGH). Medication was maintained for 6 months after completed dose
      titration. RESULTS: The FBG target was achieved in 9% of patients after diet
      alone. Single-drug therapy was insufficient in 36% and MGL in 25% (NS) of the
      randomized patients. There was further improvement in glucose control by the high
      dose combinations. Mean FBG +/- SE was reduced (P = 0.001) from 9.1 +/- 0.4 to
      7.0 +/- 0.2 mmol/l in those maintained on single-drug treatment or low-dose
      primary combination. Those treated with different high-dose combinations had a
      large mean FBG reduction, from 13.3 +/- 0.8 to 7.8 +/- 0.6 mmol/l. HbA1c levels
      showed corresponding reductions, and glycemic levels rose after drug
      discontinuation. Fasting C-peptide rose during treatment with G and MGL but not
      with M, while fasting insulin was not significantly changed. Meal-stimulated C
      peptide and insulin levels were unchanged by M but increased by G and, to a
      lesser extent, by MGL. There were no significant insulin or C-peptide differences
      between the different high-dose combinations (M/G, G/M, and MGH). Body weight did
      not change following treatment with M or combination but increased by 2.8 +/- 0.7
      kg following G alone. Blood pressure was unchanged. Overall effects on plasma
      lipids were small, with no significant differences between groups. Drug safety
      was satisfactory, even if the reporting of (usually modest) adverse events was
      high; the profile, but not the frequency, differed between groups. CONCLUSIONS:
      Dose-effect titrated treatment with either metformin or glyburide promotes equal
      degrees of glycemic control. The former, but not the latter, is able to achieve
      this control without increasing body weight or hyperinsulinemia. Near-normal
      glycemia can be obtained by a combination of metformin and sulfonylurea, even in
      advanced NIDDM.

PMID- 7821130
TI  - Combined analysis of islet cell antibodies that cross-react with mouse pancreas,
      antibodies to the M(r) 64,000 islet protein, and antibodies to glutamate
      decarboxylase in type I diabetic patients.
AB  - OBJECTIVE: A combined analysis of whether islet cell autoantibodies (ICAs) are
      cross-reactive with mouse pancreas, with glutamate decarboxylase (GAD)
      antibodies, and with 64K antibodies was performed in a large sample of recently
      diagnosed type I diabetic patients. The disappearance rates of these different
      autoantibodies were compared in some patients after onset of the disease. The
      aims were to determine patterns in GAD/64K antibodies with regard to cross
      species reaction of ICA and to assess whether GAD could contribute to ICA
      positivity in mouse and human pancreases and whether the simultaneous search for
      all the antibody specificities enhances the detection of autoimmune stigma.
      RESEARCH DESIGN AND METHODS: ICA detected by immunofluorescence in human and
      mouse pancreases, antibodies immunoprecipitating the 64K rat islet antigen, and
      antibodies immunotrapping brain GAD activity were quantified at diagnosis of
      diabetes in 95 patients and in sequential samples during 1 year after diagnosis
      in 13 patients. The contribution of GAD to ICA positivity in mouse and human
      pancreases was evaluated by the analysis of correlations between tests and by the
      ability of brain homogenate to block ICA reactivity in pancreases from both
      species. RESULTS: ICAs were detected in human pancreases in sera from 63 (66%)
      patients, among which 61% bound also to a mouse pancreas. GAD and 64K antibodies
      were strongly correlated (P < 0.0001) and were detected in 69 and 73% of the
      patients, respectively. All but two patients with ICA in human pancreas also
      displayed either ICA in mouse pancreas or GAD/64K antibodies. Among 32 patients
      without ICA in human pancreas, 54% displayed either GAD/64K antibodies or ICA in
      mouse pancreas. Only 16% of the patients displayed neither ICA nor GAD/64K
      antibodies. A correlation (P < 0.005) was found between ICA in human and mouse
      pancreases. GAD or 64K antibodies were strongly correlated with ICA in human
      pancreas (P < 0.0001), but not with ICA in mouse pancreas. After preincubation of
      six sera with GAD-containing brain homogenate, ICA titers were unaffected in
      mouse pancreas but reduced in human pancreas. ICA titers in mouse pancreas were
      decreased after 3 months (P < 0.01) in diabetic patients, contrasting with the
      stability of ICA in human pancreas and GAD antibodies by 1 year after diagnosis.
      CONCLUSIONS: According to cross-species reaction, we confirm the heterogeneity of
      ICA in a large series of type I diabetic patients, ICAs that cross-reacted with
      mouse pancreas being more frequent than ICAs without cross-species reactivity.
      GAD and 64K antibodies were also present in a majority of patients. The
      simultaneous search for all the antibody specificities enhances the detection of
      autoimmune stigma so that only a few patients did not display any autoantibody at
      diagnosis. GAD is not the target of ICAs in mouse pancreas, whereas GAD accounts
      for ICA positivity in human pancreas. The conclusion that ICAs in mouse pancreas
      are not GAD-reactive is reinforced by the fact that they are more transient after
      onset of diabetes than are GAD antibodies or the complex mixture of ICAs in human
      pancreas.

PMID- 7821129
TI  - The effect of recurrent practice at home on the acceptability of capillary blood
      glucose readings. Accuracy of self blood glucose testing.
AB  - OBJECTIVE: To judge how reliably patients perform capillary blood glucose testing
      over time with recurrent practice at home and to assess if a clinic glucose meter
      is an acceptable alternative to the clinical laboratory for monitoring patient
      performance. RESEARCH DESIGN AND METHODS: We compared capillary blood glucose
      readings obtained by patients with their own equipment and the venous blood
      glucose determinations by the clinical laboratory at three biweekly visits during
      the initial phase in 40 subjects attending the diabetes clinic at the Veterans'
      Affairs Medical Center in Phoenix, Arizona. We also compared patient-generated
      readings using their own equipment and the readings obtained by the clinic
      glucose meter and strips at five weekly visits during the second phase in 11
      subjects who continued further participation. Error grid analysis was used for
      both comparisons. Capillary blood glucose readings obtained with clinic glucose
      meter and strips on one hand were correlated with venous blood glucose levels
      determined by the clinical laboratory. RESULTS: During the initial phase, 30
      subjects consistently obtained clinically acceptable comparisons (zone A on the
      error grid, i.e., within 20% of the laboratory value) or improved over time, 9
      subjects showed deterioration, and 1 subject failed to obtain zone A results on
      any of the visits. Three subjects who had consistently obtained zone A results
      during the initial phase maintained their performance, whereas eight subjects who
      had failed to achieve zone A values by the end of the initial phase gradually
      improved and ultimately achieved zone A values by the end of the study. A highly
      significant correlation was noted between clinic meter readings and laboratory
      values (r = 0.93, P < 0.00001). CONCLUSIONS: Clinically acceptable user
      proficiency in capillary blood glucose testing can be maintained in most
      subjects, with recurrent intensive education during follow-up clinic visits.
      Therefore, we recommend that these comparisons be performed and patient's
      technique be observed at each visit to monitor their performance. The clinic
      glucose meter is a suitable alternative to a clinical laboratory for user
      proficiency checks.

PMID- 7821132
TI  - The relationship between serum lipoprotein(a) and insulinemia in healthy
      nondiabetic adult men.
AB  - OBJECTIVE: To test the hypothesis that variations in serum insulin concentrations
      and insulin action may influence serum concentrations of lipoprotein(a) [Lp(a)].
      RESEARCH DESIGN AND METHODS: A cross-sectional analysis of fasting serum insulin
      and Lp(a) concentrations were conducted in a group of 54 healthy adult men 23-61
      years of age. Measures of dietary intake, exercise, smoking, alcohol ingestion,
      body mass index (BMI), fasting plasma lipoprotein lipid concentrations, and serum
      sex hormone and fasting glucose levels were also determined. RESULTS: The fasting
      serum concentrations of insulin and Lp(a) were negatively correlated (r = -0.339,
      P = 0.014) by univariate regression analysis. Several confounding variables were
      also significantly correlated with Lp(a) concentrations: testosterone (r = 0.348,
      P = 0.012), strenuous exercise (r = 0.287, P = 0.041), and BMI (r = -0.276, P =
      0.050). As expected, these additional variables and serum insulin concentrations
      were highly interrelated. In a stepwise regression model, the serum insulin level
      was identified as the single best predictor of Lp(a) levels. Nearly 25% of the
      heterogeneity in serum concentrations of Lp(a) could be predicted by serum levels
      of insulin and testosterone, BMI, and the amount of strenuous exercise.
      CONCLUSIONS: The results of these studies have shown that serum concentrations of
      insulin and testosterone, BMI, and strenuous exercise appear to account for the
      majority of predicted nongenetic variability in serum levels of Lp(a). These
      observations suggest the possibility in this group of healthy men that serum
      concentrations of Lp(a) may be modulated by a complex interplay between insulin
      action, obesity, androgen levels, and strenuous exercise.

PMID- 7821133
TI  - Improved visual evoked potential latencies in poorly controlled diabetic patients
      after short-term strict metabolic control.
AB  - OBJECTIVE: To determine whether short-term strict control of blood glucose can
      improve abnormal visual evoked potentials (VEPs) in poorly controlled diabetic
      patients with no overt diabetic complications. RESEARCH DESIGN AND METHODS: VEPs
      (P100 wave latencies) were recorded in 12 poorly controlled diabetic patients (7
      with insulin-dependent diabetes mellitus and 5 with non-insulin-dependent
      diabetes mellitus) before and after at least 3 days of near normoglycemia
      obtained by continuous subcutaneous insulin infusion (CSII). Exclusion criteria
      were overt diabetic neuropathy or retinopathy. The control subjects were 12
      healthy subjects matched for age and sex. Fifty-two other subjects formed a
      reference control population. The intra-individual coefficient of variation for
      P100 latency was < 3%. RESULTS: The P100 latencies were longer in diabetic
      patients than in control subjects (means of both eyes +/- SD: 116.8 +/- 10.1 vs.
      106.2 +/- 4.5 ms, P < 0.01), and 4 of the 12 diabetic patients had abnormal VEPs.
      After 3 days of close blood glucose control (mean blood glucose profile fell from
      13.7 +/- 2.2 mmol/l to 6.8 +/- 1.2 mmol/l, P < 0.01), the mean P100 latencies
      were significantly shorter (112.5 +/- 7.6 ms, P < 0.01) but were still
      significantly longer than control values. The longer the initial P100 latency,
      the greater the decrease after CSII. There was no correlation between the fall in
      blood glucose and improvement in VEPs. CONCLUSIONS: Short-term blood glucose
      normalization is associated with improved P100 wave latency in uncomplicated
      diabetic patients. These data suggest that abnormal VEPs are partly reversible
      and include functional disturbances related to glucose metabolism.

PMID- 7821131
TI  - Community diabetes care. A 10-year perspective.
AB  - OBJECTIVE: To compare diabetes care and education at the community level in 1981
      and 1991 in order to record progress achieved in the decade of the 1980s,
      determine if there is a gap that must be closed to reach diabetes-related
      objectives for 2000, and establish a baseline to which changes stimulated by the
      Diabetes Control and Complications Trial can be compared. RESEARCH DESIGN AND
      METHODS: In eight Michigan communities, representative primary-care physicians
      (61 in 1981; 68 in 1991) and their diabetic patients (428 and 440) were
      identified. Communities, physicians, and patients were randomly selected.
      Participating patients were interviewed and examined in their community or home
      to assess the kind and extent of diabetes care they had been receiving; their
      metabolic, nutritional, educational, and psychosocial status; their diabetic
      history and current status; and other related factors. The diabetic status, care,
      and education of the 1981 community patients were compared with those of patients
      studied in 1991. RESULTS: Positive changes in diabetes care and education at the
      community level from 1981 to 1991 were seen in the areas of patient glucose
      monitoring, insulin administration practices, hypertension control, exercise
      recommendations in diabetic management; and smoking rates. Negative changes
      occurred in the percentage of non-insulin-dependent diabetes mellitus (NIDDM)
      patients receiving diabetes education and frequency of office visits to the
      patient's primary-care physician. Changes of indeterminate value included a sharp
      decline in primary diabetes admissions to the hospital and a decrease in the
      proportion of NIDDM patients managed with insulin. Many other hoped-for changes
      from 1981 status, such as screening for retinopathy, foot-care practices, and
      overall metabolic control of diabetes, did not occur. CONCLUSIONS: The decade of
      the 1980s produced modest, but not impressive, improvements in diabetes care and
      education at the community level. Progress must be accelerated if the diabetes
      related objectives included in the national targets for health promotion and
      disease prevention for 2000 are to be met.

PMID- 7821135
TI  - Perinatal determinants among children who later develop IDDM.
AB  - OBJECTIVE: The aim of this study was to investigate whether children who develop
      insulin-dependent diabetes mellitus (IDDM) differ in some aspects from a matched
      control group at the time of birth. RESEARCH DESIGN AND METHODS: We studied all
      children who were born in Denmark during the period 1973-1977 and admitted to a
      Danish hospital with a diagnosis of IDDM during 1978-1989. The study was
      conducted by combining two nationwide registries, The National Patient Registry
      and The Birth Registry. RESULTS: The criteria were fulfilled by 837 children.
      Data regarding the age of the parents, the number of previous pregnancies of the
      mother, the month of birth, and the birth weight and length of the children who
      developed IDDM were compared with the data of an age- and sex-matched control
      group of 837 children without IDDM. We did not detect any significant differences
      between the two groups with respect to the parameters studied. CONCLUSIONS: No
      differences in perinatal determinants could be demonstrated among Danish children
      who develop IDDM compared with children without diabetes.

PMID- 7821134
TI  - Glycemic control in a sample of black and white clinic patients with NIDDM.
AB  - OBJECTIVE: To compare glycemic control of black and white patients under
      treatment for non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN
      AND METHODS: Medical records of patients with NIDDM were reviewed at 19 of 24
      clinics or health centers in a specified area of north central Florida. Data were
      abstracted from the charts of all non-Hispanic black (n = 248) or white (n = 280)
      patients who met preset eligibility criteria. RESULTS: The mean +/- SD age was 58
      +/- 14 years; the mean +/- SD duration of diabetes was 9 +/- 7.5 years. Of 528
      patients, 220 were treated with oral hypoglycemic agents, 269 were treated with
      insulin, 28 were treated with diet alone, and 11 were treated with a combination
      of oral agents, diet, and insulin. Glycosylated hemoglobin was > or = 8% for 47%
      of black women, 41% of black men, 38% of white men, and 29% of white women. The
      less favorable control status of the black women persisted within categories of
      age (40-59 years or > or = 60 years), treatment (insulin or oral hypoglycemic
      agents), time since diagnosis (less than versus greater than or equal to the
      median of 7 years), and obesity (noted versus not noted in chart). In multiple
      logistic regression analyses controlling simultaneously for these variables, the
      odds (95% confidence interval [CI]), compared with white women, of having
      glycosylated hemoglobin > or = 8% were 2.2 (1.4, 3.4) for black women and 1.5
      (0.8, 2.9) and 1.4 (0.8, 2.5) for black and white men, respectively. CONCLUSIONS:
      Black women were more likely than white women or men to have glycosylated
      hemoglobin > or = 8%. This difference was not readily explained by age, type of
      treatment, time since diagnosis, or a notation of obesity in the medical record,
      although an effect of obesity cannot be excluded on this basis.

PMID- 7821136
TI  - Frequency and determinants of screening for diabetes in the U.S.
AB  - OBJECTIVE: To determine the prevalence of risk factors for non-insulin-dependent
      diabetes mellitus (NIDDM) and the frequency of screening for NIDDM in U.S.
      adults. RESEARCH DESIGN AND METHODS: A detailed questionnaire was administered to
      a representative sample of 19,680 adults > or = 18 years of age who reported no
      medical history of diabetes in the 1989 National Health Interview Survey (NHIS).
      Information was obtained on risk factors for diabetes, complications related to
      diabetes, and whether the subjects had been screened for diabetes in the past
      year. Women reporting pregnancy in the past year were excluded from analysis. The
      prevalence of undiagnosed NIDDM according to the frequency of risk factors for
      NIDDM was determined based on oral glucose tolerance data from the National
      Health and Nutrition Examination Survey (NHANES) II and Hispanic Health and
      Nutrition Examination Survey (HHANES). RESULTS: Prevalence of undiagnosed NIDDM
      based on the NHANES II and HHANES increased with age, obesity, and family history
      of diabetes, reaching 11.7% in people with all three risk factors. Based on the
      NHIS, 77.5% of U.S. adults with no medical history of diabetes (131 million
      people) had at least one risk factor for NIDDM or complication related to NIDDM,
      and 22.9% (38 million people) had three or more risk factors or complications.
      Approximately 31% of adults reported being screened for diabetes in the past
      year. Screening rates increased with an increasing number of risk factors, but
      even among those with three risk factors, only 38.6% were screened for NIDDM.
      CONCLUSIONS: More than 7 million U.S. adults have undiagnosed NIDDM.
      Nevertheless, screening for diabetes in high-risk groups occurs substantially
      less frequently than necessary to detect undiagnosed NIDDM and institute
      appropriate hypoglycemic treatment.

PMID- 7821137
TI  - Greater effect of diabetes on LDL size in women than in men.
AB  - OBJECTIVE: Coronary heart disease (CHD) is increased two- to fourfold in subjects
      with NIDDM compared with normoglycemic subjects. This excess risk is only
      partially explained by conventional risk factors. We studied the effect of non
      insulin-dependent diabetes mellitus (NIDDM) on the size of low-density
      lipoproteins (LDL). RESEARCH DESIGN AND METHODS: We examined the effect of NIDDM
      on LDL size and subclass pattern B (LDL size < 253.5 A) in 95 diabetic subjects
      and 371 nondiabetic subjects from the San Antonio Heart Study, a population-based
      study of diabetes and cardiovascular disease. RESULTS: LDL size (A) was
      significantly lower in diabetic subjects (men: 252.2 +/- 1.8; women: 254.7 +/-
      1.3) than in nondiabetic subjects (men: 256.1 +/- 0.8; women: 259.7 +/- 0.7) (P =
      0.007). After the use of analysis of covariance to adjust for triglyceride and
      high-density lipoprotein cholesterol, LDL size was still significantly lower in
      diabetic women than in nondiabetic women. In men, however, diabetes was no longer
      significantly associated with LDL size after similar adjustments. Fasting glucose
      was more strongly correlated with LDL size in women (r = -0.30) than in men (r = 
      0.18). CONCLUSIONS: We conclude that LDL size is significantly lower in diabetic
      subjects of both sexes than in nondiabetic subjects, but that diabetic
      dyslipidemia accounts for the association in diabetic men. The stronger
      association between LDL size and diabetes in women than in men may partially
      explain the greater relative risk of CHD observed in women with NIDDM in some
      studies.

PMID- 7821138
TI  - Risk factors for distal symmetric neuropathy in NIDDM. The San Luis Valley
      Diabetes Study.
AB  - OBJECTIVE: To investigate risk factors for distal symmetric (sensory) neuropathy
      among prevalent cases of non-insulin-dependent diabetes mellitus (NIDDM) in a
      population-based study in southern Colorado. RESEARCH DESIGN AND METHODS:
      Prevalent neuropathy was identified in 77 of 277 people with NIDDM by a
      standardized history and neurologic examination. Fifteen known or suspected risk
      factors for neuropathy were determined without knowledge of neuropathy status.
      RESULTS: Older age at examination, longer duration of diabetes, higher
      glycohemoglobin percentage, lower fasting C-peptide, insulin use, and presence of
      retinopathy and nephropathy (microalbumin > or = 200 micrograms/ml) were all
      significantly associated with neuropathy. Sex, ethnicity (Hispanic versus non
      Hispanic white), height, systolic blood pressure, peripheral vascular disease,
      cigarette and alcohol use, and serum lipid levels were not significantly
      associated with neuropathy. In a multivariate logistic model, increasing age
      (odds ratio [OR] = 1.3, 95% confidence interval [CI] = 1.1-1.6), longer duration
      of diabetes (OR = 1.3, CI = 1.0-1.6), increased glycohemoglobin percentage (OR =
      1.5, CI = 1.1-2.1), and insulin use (OR = 2.8, CI = 1.3-6.1) were associated with
      neuropathy. Retinopathy (OR = 3.0, CI = 1.2-7.7), but not nephropathy, was
      important when added to this model. CONCLUSIONS: Worse glycemic control and
      insulin use were independently associated with neuropathy in people with NIDDM.
      Whether insulin use represents another marker for severity of the metabolic
      disturbance or is an independent risk factor for neuropathy requires further
      study. We could not confirm associations of neuropathy with height, with
      nephropathy, or with retinopathy, independent of duration of diabetes.

PMID- 7821139
TI  - Insulin omission in women with IDDM.
AB  - OBJECTIVE: To describe the extent of intentional insulin omission in an
      outpatient population of women with insulin-dependent diabetes mellitus (IDDM)
      and examine its relationship to disordered eating, attitudes toward diabetes,
      other psychosocial factors, long-term complications, and glycemic control.
      RESEARCH DESIGN AND METHODS: Before their routinely scheduled clinic
      appointments, female IDDM patients who were 13-60 years of age completed a self
      report survey (final n = 341). The survey included standardized questionnaires
      assessing disordered eating attitudes and behaviors, psychological functioning
      (general distress, diabetes-specific distress, and hypoglycemic fear), attitudes
      toward diabetes, and self-care behaviors. All subjects were assessed for
      glycosylated hemoglobin within 30 days of survey completion. Long-term
      complications were determined through chart review. RESULTS: Approximately 31% of
      the subject sample, representing women of all ages, reported intentional insulin
      omission, but only 8.8% reported frequent omission. Compared with non-omitters,
      omitters reported more disordered eating, greater psychological distress (general
      and diabetes-specific), more hypoglycemic fear, poorer regimen adherence, and
      greater fears concerning improved diabetes management (which may lead to weight
      gain). Omitters evidenced poorer glycemic control, more diabetes-related
      hospitalizations, and higher rates of retinopathy and neuropathy. Multivariate
      examination revealed only two variables that independently predicted omission:
      diabetes-specific distress and fear of improved glycemic control ("because I will
      gain weight"). Of the omitters, approximately half reported omitting insulin for
      weight-management purposes (weight-related omitters). These subjects evidenced
      significantly greater psychological distress, poorer regimen adherence (including
      more frequent omission), poorer glycemic control, and higher rates of
      complications than did non-weight-related omitters as well as non-omitters. Non
      weight-related omitters tended to fall between weight-related omitters and non
      omitters on most measures of psychological functioning, adherence, and glycemic
      control. CONCLUSIONS: These findings suggest that insulin omission is common,
      that it is not limited to younger women, and that the medical consequences of
      omission, especially frequent omission, may be severe. Although a strong
      association between omission and disordered eating was observed, these data
      suggest that this link may be complicated by important diabetes-specific factors.
      Patients preoccupied with eating and weight concerns may also become emotionally
      overwhelmed by diabetes and/or fearful of normoglycemia (and the associated
      weight-related consequences), thus reinforcing the desire to omit insulin and
      maintain elevated blood glucose levels.

PMID- 7821140
TI  - Insulin withholding for weight control in women with diabetes.
AB  - OBJECTIVE: To provide a description of the clinical characteristics that
      distinguish individuals who withhold insulin for weight control from those who do
      not. Some individuals with insulin-dependent diabetes mellitus (IDDM) control
      their weight by withholding insulin and purging excessive calories. This process
      places patients at risk for developing severe hyperglycemia, diabetic
      ketoacidosis, and increases the risk of long-term complications of diabetes.
      RESEARCH DESIGN AND METHODS: Forty-two women with IDDM, ages 16-40, were
      interviewed and divided into two groups: insulin withholders (IWs) and non
      insulin withholders (non-IWs). These groups were compared on physiological,
      behavioral, psychological, and psychiatric variables. RESULTS: Compared with non
      IWs, patients who withheld insulin to control their weight exhibited poorer
      glycemic control, reported more negative attitudes toward diabetes, were more
      likely to have pathological scores on the Eating Disorder Inventory 2, and were
      more likely to report current or past symptoms of anorexia or bulimia nervosa.
      IWs were also more likely to report lying to physicians about their degree of
      compliance with their diabetes regimens. CONCLUSIONS: The results of this study
      indicated that IWs exhibit more symptoms associated with the spectrum of eating
      disorders than non-IWs. This study showed that insulin withholding for weight
      control not only exists, but is associated with some maladaptive symptoms and
      behaviors that need to be addressed by diabetes treatment teams.

PMID- 7821141
TI  - High prevalence of NIDDM and IGT in an elderly south Indian population with low
      rates of obesity.
AB  - OBJECTIVE--To assess the prevalence of diabetes and impaired glucose tolerance
      (IGT) in the urban and rural elderly population in south India. RESEARCH DESIGN
      AND METHODS--Urban and rural populations > or = 60 years of age and
      representative of the areas (873 urban and 588 rural subjects) were screened for
      diabetes and IGT using fasting and 2-h postglucose capillary blood glucose
      measurements. RESULTS--In the urban area, 211 (23.7%) had diabetes, and 101
      (12.4%) had IGT. In the rural area, 56 (9.9%) had diabetes, and 82 (14.9%) had
      IGT. The ratio of newly diagnosed to known diabetes was 1:3 in the urban and 1:1
      in the rural areas. Positive family history of diabetes, body mass index (BMI),
      subscapular-to-triceps ratio, and waist-to-hip ratio were significantly
      associated with diabetes in the urban population. Only age and BMI showed
      significant association with diabetes in the elderly rural population. None of
      the tested parameters, except age in the urban subjects, showed association with
      IGT. CONCLUSIONS--This study highlights the high prevalence of glucose
      intolerance in elderly south Indians having low mean BMI (mean +/- SD; urban 21.7
      +/- 4.6, rural 17.9 +/- 3.3 kg/m2). Although there was a twofold higher
      prevalence of diabetes in the urban area, the occurrence of IGT was similar in
      urban and rural populations.

PMID- 7821142
TI  - Incidence of type I diabetes in the Liguria Region, Italy. Results of a
      prospective study in a 0- to 14-year age-group.
AB  - OBJECTIVE: To assess updated incidence of insulin-dependent diabetes mellitus
      (IDDM) in 0- to 14-year-old children in Liguria, a northwest region of Italy.
      RESEARCH DESIGN AND METHODS: Incident cases were recorded prospectively from 1987
      to 1991. Incidence rates (IRs) were directly standardized on the basis of the
      1990 world population. The independent effect of age, sex, residence, and
      calendar year was estimated with a Poisson regression model. The degree of
      ascertainment was calculated in accordance with the capture/recapture method.
      RESULTS: During 5 full calendar years, 117 new cases of IDDM in children were
      diagnosed in Liguria. The standardized IR over the 5-year period was 11.72
      cases.100,000(-1).year-1. The sex-specific IR among males and females was 11.45
      and 12.01, respectively. The age-specific IR was higher in the 5-9 age-group.
      CONCLUSIONS: The IR of IDDM in Liguria is among the highest in southern Europe
      and approaches that of northern European countries. In particular, it is much
      higher than those reported in the surrounding Italian regions, except for
      Sardinia. Therefore, the geographical distribution of IDDM does not seem to
      reflect the simple north-south gradient reported in several previous studies.

PMID- 7821143
TI  - A comparison of eating behaviors in newly diagnosed NIDDM patients and case
      matched control subjects.
AB  - OBJECTIVE: To determine whether disordered eating may be problematic in non
      insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: We
      contrasted the eating behaviors and attitudes in 50 newly diagnosed NIDDM
      patients with 50 age-, sex-, and weight-matched control subjects. RESULTS:
      Although 14% of diabetic subjects versus 4% of nondiabetic subjects reported
      episodes of binge eating (P < 0.10), there was no difference between diabetic and
      nondiabetic subjects in the prevalence with which they met criteria for binge
      eating disorder. Diabetic patients with a history of binge eating were
      significantly heavier, had younger age at diagnosis, and had more problems with
      eating in response to situational and emotional cues than did diabetic patients
      who did not binge. CONCLUSIONS: No support was found for greater prevalence of
      binge eating disorder in newly diagnosed NIDDM patients than in matched
      nondiabetic control subjects.

PMID- 7821144
TI  - Differences in peripheral and autonomic nerve function measurements in painful
      and painless neuropathy. A clinical study.
AB  - OBJECTIVE: To examine the differences in peripheral and autonomic nerve function
      measurements between diabetic patients without neuropathy (group 1, n = 38, mean
      age 50.9, range 29-71 years), with painless neuropathy (group 2, n = 32, mean age
      49.2, range 30-71 years), and with painful neuropathy (group 3, n = 52, mean age
      51.5, range 28-73 years). RESEARCH DESIGN AND METHODS: The evaluation of
      neuropathy was based on clinical symptoms, signs, and quantitative sensory
      testing, including current perception threshold (CPT) with a neurometer and
      electrophysiology. RESULTS: The Neuropathy Symptom Score and the Neuropathy
      Disability Score were higher in patients with painful neuropathy compared with
      patients with painless neuropathy (6.8 +/- 2.7 vs. 0.5 +/- 0.8 [mean +/- SD], P <
      0.0001, and 12.5 +/- 6.2 vs. 8.6 +/- 6.8, P < 0.01, respectively). In contrast,
      no differences were found in the quantitative sensory testing, including CPT
      measurements, the electrophysiological measurements, and the autonomic nerve
      system function tests in the two groups. Significant differences were found in
      all the above measurements when groups 2 and 3 were compared with diabetic
      patients without neuropathy (group 1). When all diabetic patients were considered
      as one group, significant correlations were found between CPT and the other
      peripheral nerve function assessments. In particular, peroneal nerve motor
      conduction velocity correlated with CPT at 2 kHz (r = -0.48, P < 0.001) and
      vibration perception threshold (r = -0.50, P < 0.001). CONCLUSIONS: We conclude
      that no difference could be found in the function of small and large nerve fibers
      between painful and painless diabetic neuropathy using conventional tests
      currently used. The CPT evaluation failed to quantify painful symptoms, but it
      compared favorably with other quantitative sensory tests in quantifying
      peripheral neuropathy.

PMID- 7821145
TI  - Effects of postprandial exercise on glycemic response in IDDM subjects. Studies
      at constant insulinemia.
AB  - OBJECTIVE: To determine the influence of postprandial exercise on blood glucose
      responses in insulin-dependent diabetes mellitus (IDDM) subjects. RESEARCH DESIGN
      AND METHODS: Two identical test meals were served with a 7-day interval. On one
      occasion, a 30-min cycle exercise was performed 15 min after the meal. Patients
      had achieved normoglycemia by means of an artificial pancreas (Biostator) before
      the meals, which also ensured constant insulin infusion in the study periods.
      Seven IDDM subjects attending the outpatient clinic at Aarhus Kommunehospital
      were studied. RESULTS: The 30 min of cycling reduced postprandial blood glucose
      response areas by 34 +/- 12% (P < 0.01) from 638 +/- 30 to 492 +/- 61 mmol/l x
      180 min (P < 0.03), whereas similar peak blood glucose values were found (13.7 +/
      0.3 vs. 12.0 +/- 1.3 mmol/l). CONCLUSIONS: Thirty minutes of moderate exercise
      done postprandially reduces the blood glucose response to 50 g carbohydrate by
      about one-third.

PMID- 7821146
TI  - Shanghai, China, has the lowest confirmed incidence of childhood diabetes in the
      world.
AB  - OBJECTIVE: To determine the incidence of insulin-dependent diabetes mellitus in 0
      to 14-year-old children in Shanghai, China, from 1980 to 1991. RESEARCH DESIGN
      AND METHODS: Data were collected from hospitals with pediatric departments. The
      secondary source of validation was primary and middle schools. RESULTS: The
      average crude annual incidence rate was 0.61/100,000 (95% confidence interval,
      0.48-0.77). The ascertainment-corrected incidence rates were 0.72/100,000 (0.57
      0.91). CONCLUSIONS: The incidence of childhood diabetes in Shanghai, China, was
      one of the lowest, if not the lowest, in the world.

PMID- 7821147
TI  - Parallels between treated uncontrolled diabetes and the refeeding syndrome with
      emphasis on fluid and electrolyte abnormalities.

PMID- 7821148
TI  - Type I diabetes masquerading as type II diabetes. Possible implications for
      prevention and treatment.
AB  - Type I diabetes is probably due to the immune-mediated destruction of islet
      insulin-secreting beta-cells. This chronic destructive process is associated with
      both cellular and humoral immune changes in the peripheral blood that can be
      detected months, even years, before the onset of clinical diabetes. Throughout
      this prediabetic period, metabolic changes, including altered glucose tolerance
      and reduced insulin secretion, deteriorate at variable rates toward full-blown
      diabetes. The ability to predict subsequent clinical diabetes in those
      nondiabetic individuals with immune and metabolic changes has led to attempts to
      prevent the disease onset by therapeutic intervention. A small fraction of
      individuals with immune changes develop clinical diabetes that does not require
      insulin treatment. The onset of diabetes in these cases is usually in adult life,
      and because their diabetes is, at least initially, not insulin-dependent, they
      appear clinically to have type II diabetes. Such patients probably have the same
      disease process as patients with type I diabetes in that they have similar human
      leukocyte antigen (HLA) genetic susceptibility as well as autoantibodies to islet
      antigens. It is proposed that non-insulin-dependent diabetic patients who have
      markers that characterize individuals at risk of type I diabetes may be suitable
      candidates for those same therapeutic strategies that seek to prevent progression
      to insulin-dependence or even to reestablish normal glucose tolerance.

PMID- 7821150
TI  - Determination of the area under a curve.

PMID- 7821149
TI  - Islet cell antibodies. Light at the end of the tube?

PMID- 7821151
TI  - Comments on Tai's mathematic model.

PMID- 7821152
TI  - Modeling metabolic curves.

PMID- 7821153
TI  - Revision of improved mean glycemia from HbA1c.

PMID- 7821154
TI  - Prevalence and clinical characteristics of type I and type II insulin-treated
      diabetes in the community.

PMID- 7821155
TI  - Silent coronary artery disease in diabetic patients with cardiac autonomic
      neuropathy.

PMID- 7821156
TI  - Behavioral correlates of metabolic control in people with IDDM in Taipei.

PMID- 7821157
TI  - IDDM incidence in children 0-14 years of age in Piedmont, Italy.

PMID- 7821158
TI  - Resuspension of intermediate-acting insulin as a source of error in insulin
      dosing.

PMID- 7821159
TI  - Severe or life-threatening hypoglycemia in insulin pump treatment.

PMID- 7821160
TI  - American Diabetes Association meetings, 1994. Insulin-dependent diabetes
      mellitus.

PMID- 7821161
TI  - Calling all physicians for the Diabetes Prevention Trial-Type I.

PMID- 7821162
TI  - Prevalence of arterial hypertension in diabetic patients before and after the JNC
      V.
AB  - OBJECTIVE: To compare the prevalence of arterial hypertension in patients with
      insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes
      mellitus (NIDDM) according to blood pressure (BP) criteria from the World Health
      Organization (WHO) and The Fifth Report of the Joint National Committee on
      Detection, Evaluation and Treatment of High Blood Pressure (JNC-V). RESEARCH
      DESIGN AND METHODS: Two cohorts of Caucasian patients attending the outpatient
      clinic at Hvidore Hospital were identified: 1) 957 patients with IDDM; 53% men,
      40 (18-75) years of age (mean [range]); and 2) 549 patients with NIDDM; 53% men,
      60 (20-76) years of age. BP was measured at least yearly, while patients rested
      in a sitting position, with a standard clinical sphygmomanometer. Patients were
      classified as hyper- or normotensive based on average BP during a 3-year follow
      up period. Patients receiving antihypertensive treatment were classified as
      hypertensives. RESULTS: In IDDM patients, the prevalence of arterial hypertension
      rose from 15 to 42% in the normoalbuminuric group, from 26 to 52% in the
      microalbuminuric group, and from 61 to 79% in the macroalbuminuric group when WHO
      and JNC-V criteria were compared. The corresponding rises in NIDDM patients were
      from 51 to 71% (normo-), from 73 to 90% (micro-), and from 82 to 93%
      (macroalbuminuria). Of the untreated hypertensive patients, 78% of IDDM patients
      and 50% of NIDDM patients had stage 1 (140-159/90-99 mmHg) hypertension; 20% of
      IDDM patients and 37% of NIDDM patients had stage 2 (160-179/100-109 mmHg)
      hypertension. Two out of three untreated hypertensive patients had isolated
      systolic hypertension. CONCLUSIONS: The new JNC-V criteria approved by the
      American Diabetes Association leads to a considerable increase in the prevalence
      of arterial hypertension in a population of IDDM and NIDDM patients. Isolated
      systolic hypertension contributes importantly.

PMID- 7821163
TI  - Medial artery calcification predicts cardiovascular mortality in patients with
      NIDDM.
AB  - OBJECTIVE: To study the predictive value of medial artery calcification
      (Monckeberg's sclerosis) in relation to 10-year cardiovascular mortality in
      patients with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN
      AND METHODS: We studied the predictive value of thigh medial and intimal artery
      calcifications to 10-year cardiovascular mortality in a well-characterized group
      of 133 middle-aged, newly diagnosed patients with NIDDM (70 men and 63 women).
      RESULTS: At baseline, medial artery calcifications were found in 17% of the
      patients and intimal-type calcifications were found in 23%. During the follow-up,
      21% of the diabetic patients died from cardiovascular causes. The age-adjusted
      odds ratio for cardiovascular mortality was 4.2 (95% confidence intervals: 1.5
      11.3) for medial-type and 1.6 (0.6-4.3) for intimal-type calcifications. In
      multiple logistic regression analysis, including age, sex, systolic blood
      pressure, low-density- and high-density-lipoprotein cholesterol, very-low-density
      lipoprotein triglycerides, smoking, body mass index, fasting serum insulin, blood
      glucose, urinary albumin, and ischemic ECG changes, as well as the intimal artery
      calcification, the medial artery calcification was the dominant factor predicting
      cardiovascular mortality. CONCLUSIONS: In this study medial artery calcification
      was a strong independent predictor of cardiovascular mortality in patients with
      newly diagnosed NIDDM. Whether these subjects had a longer duration of
      hyperglycemia before the diagnosis than those without medial artery
      calcifications remains unknown.

PMID- 7821164
TI  - Comparison of excess costs of care and production losses because of morbidity in
      diabetic patients.
AB  - OBJECTIVE: To assess and compare excess costs of care and production losses
      because of morbidity in diabetic patients and the general population of a Swedish
      community. RESEARCH DESIGN AND METHODS: Costs of production losses were
      calculated from medical and social insurance records on sickness benefit days
      (short-term illness) and premature retirement (permanent disability) in people
      with diabetes and in the entire population of the community (a municipality
      comprising a town and rural surroundings, with 28,000 inhabitants). Care costs
      included those of consultations and inpatient care, as well as costs of insulin,
      oral antidiabetic medications, other drugs, test material, and treatment devices,
      and they were obtained from patient records, the health care administration, and
      the statistics of community pharmacy sales. RESULTS: Of the diabetic patients <
      65 years of age, above which both diabetic and nondiabetic people get retirement
      pension, and sickness benefits cease, 62% of those on insulin treatment in each
      gender had insulin-dependent diabetes mellitus (IDDM). All insulin-treated non
      insulin-dependent diabetes mellitus (NIDDM) patients were > 40 years of age. Both
      the insulin-treated and the non-insulin-treated diabetic patients were
      prematurely retired twice as often as the average population and had twice as
      many inpatient days. The insulin-treated subjects also had twice as many sickness
      benefit days. The excess costs of production losses as a result of morbidity in
      people with diabetes were about $7,000 per individual and year. The corresponding
      excess costs of inpatient care were $800. The therapeutic expenditures for
      control of diabetes were about $600 per individual and year. If converted to U.S.
      conditions, the costs of lost production as a result of excess morbidity (< 65
      years of age) would be $12 billion and $9 billion for people with insulin-treated
      and non-insulin-treated diabetes, respectively. CONCLUSIONS: If improved
      metabolic control by intensified treatment would reduce excess morbidity in both
      IDDM and NIDDM, the predominant costs of production losses imply that intensified
      antidiabetic treatment might save costs.

PMID- 7821165
TI  - Comparison of World Health Organization and National Diabetes Data Group
      procedures to detect abnormalities of glucose tolerance during pregnancy.
AB  - OBJECTIVE: To compare the one-step procedure proposed by the World Health
      Organization (WHO) with the two-step procedure proposed by the National Diabetes
      Data Group (NDDG) for the identification of abnormalities of glucose tolerance
      during pregnancy. RESEARCH DESIGN AND METHODS: One hundred twenty-seven non
      diabetic Pima Indian women had a 75-g 2-h glucose tolerance test (WHO criteria).
      Those with an elevated 1-h glucose concentration (> or = 7.8 mmol/l) were
      referred for a 100-g 3-h glucose tolerance test (National Diabetes Data Group
      criteria). The effectiveness of the two test procedures was determined by
      comparing the frequency of macrosomia and cesarean section as outcomes of
      pregnancy. RESULTS: Of 42 women with 1-h plasma glucose concentrations > or = 7.8
      mmol/l, 13 had no 100-g test, 27 had a normal test, and 2 had an abnormal test.
      Both women (100%) with abnormal two-step 100-g tests also had abnormal one-step
      75-g tests, but only 2 of the 11 women (18%) with an abnormal one-step test had
      an abnormal two-step test. Sixteen of the 127 women delivered babies weighing >
      or = 4,000 g. Six of these women (38%) were correctly identified as abnormal
      using the one-step test and one (6%) using the two-step test. Of seven women
      delivering by cesarean section, four (57%) had abnormal one-step tests, but none
      had an abnormal two-step test. CONCLUSIONS: The one-step WHO test for glucose
      tolerance during pregnancy was abnormal in a greater percentage of women with
      adverse outcomes than the more cumbersome two-step NDDG test. The one-step test
      has the added advantage of being directly comparable to the standard glucose
      tolerance test used in nonpregnant women.

PMID- 7821166
TI  - The ROC curve in the evaluation of fasting capillary blood glucose as a screening
      test for diabetes and IGT.
AB  - OBJECTIVE: To assess the performance of different cutoff points of fasting
      capillary glycemia (FCG) in the diagnosis of diabetes and impaired glucose
      tolerance (IGT) using the receiver operating characteristics (ROC) curve
      approach. RESEARCH DESIGN AND METHODS: This study included a sample of 4,019
      subjects without a previous history of diabetes who were recruited for a
      confirmatory 2-h post-glucose challenge capillary glycemia from a larger sample
      of 21,847 individuals screened with FCG. The sensitivity and the specificity of
      FCG as a screening test were analyzed in the cutoff range 3.9-8.9 mmol/l, and the
      corresponding ROC curves were plotted to assess the performance of the test.
      RESULTS: The screening test performance was better for diabetes than for IGT in
      the full range of cutoff points studied. Sensitivities ranged between 37.9 and
      97.1% for diabetes and 1.8 and 94.4% for IGT; the areas under the ROC curves were
      0.91 +/- 0.01 and 0.75 +/- 0.01, respectively. The cutoffs showing the best
      equilibrium between sensitivity and specificity approached 5.6 and 5.0 mmol/l for
      diabetes and IGT, respectively. Factors such as age, color, and family history of
      diabetes can affect the screening test performance. CONCLUSIONS: ROC curves can
      provide useful information toward improving the usefulness of FCG as a screening
      test for abnormalities of glucose tolerance.

PMID- 7821167
TI  - Structural equation modeling of symptoms, awareness and fear of hypoglycemia, and
      personality in patients with insulin-treated diabetes.
AB  - OBJECTIVE: To assess the possible influence of personality on self-reported
      awareness, symptoms, and fear of hypoglycemia and also to identify the
      relationship among these self-reported measures using formal structural equation
      modeling. RESEARCH DESIGN AND METHODS: A structured questionnaire, which included
      questions about sociodemographic details, awareness of the onset of hypoglycemia,
      and a list of symptoms of hypoglycemia, was completed by 305 consecutive insulin
      treated diabetic patients attending the diabetic clinic at the Royal Infirmary of
      Edinburgh. They also completed the Hypoglycemia Fear Survey (HFS), and
      personality was assessed using the short form of the shortened Eysenck
      Personality Questionnaire-Revised (EPQ-R). Formal structural equation modeling
      was performed using the following variables: awareness, autonomic symptoms,
      neuroglycopenic symptoms, severe hypoglycemic episodes in the last year, worry
      and behavior (from the HFS), and extroversion and neuroticism (from the short EPQ
      R). This allowed a model to be constructed that expressed the putative causal
      associations among the variables that could be tested statistically. RESULTS: Of
      the 302 patients who had experienced hypoglycemia, 111 (37%) reported reduced
      awareness, and these patients scored higher on the worry subscale of the HFS
      (reduced awareness: 41 +/- 12 vs. normal awareness: 34 +/- 12, P < 0.001). The
      patients with reduced awareness scored higher for neuroticism than did the
      patients with normal awareness (reduced awareness: 6.1 +/- 3.4 vs. normal
      awareness: 4.9 +/- 3.3, P < 0.01) and scored lower for extroversion (reduced
      awareness: 5.8 +/- 3.7 vs. normal awareness: 7.1 +/- 3.7, P < 0.01). In the
      structural equation modeling exercise, neuroticism was a significant putative
      determinant of many of the other variables. CONCLUSIONS: Personality was the
      major determinant of the variance that could be accounted for in this study and
      influenced self-reported symptoms, awareness, and fear of hypoglycemia.
      Personality factors may, therefore, influence self-reports from patients,
      particularly when soft measures, such as symptoms, are assessed and even when
      using validated clinical questionnaires. This finding stresses the importance of
      using additional evidence, such as reports from relatives, to substantiate
      reports from patients of loss of hypoglycemia awareness.

PMID- 7821168
TI  - A practical two-step quantitative clinical and electrophysiological assessment
      for the diagnosis and staging of diabetic neuropathy.
AB  - OBJECTIVE: Early diagnosis of distal symmetric sensorimotor polyneuropathy, a
      common complication of diabetes, may decrease patient morbidity by allowing for
      potential therapeutic interventions. We have designed an outpatient program to
      facilitate diagnosis of diabetic neuropathy. RESEARCH DESIGN AND METHODS:
      Patients are initially administered a brief questionnaire and screening
      examination, designated the Michigan Neuropathy Screening Instrument (MNSI).
      Diabetic neuropathy is confirmed in patients with a positive assessment by a
      quantitative neurological examination coupled with nerve conduction studies,
      designated the Michigan Diabetic Neuropathy Score (MDNS). In this study, 56
      outpatients with confirmed type I or II diabetes were administered the
      standardized quantitative components required to diagnose and stage diabetic
      neuropathy according to the San Antonio Consensus Statement (1) and the Mayo
      Clinic protocol (2). These same patients were then assessed with the MNSI and the
      MDNS. RESULTS: Of 29 patients with a clinical MNSI score > 2, 28 had neuropathy.
      Twenty-eight patients with an MDNS of > or = 7 had neuropathy, while 21 non
      neuropathic patients had a score < or = 6. Of 35 patients with diabetic
      neuropathy, 34 had > or = 2 abnormal nerve conductions. Twenty-one normal
      patients and one patient with neuropathy had < or = 1 abnormal nerve conduction.
      CONCLUSIONS: The results indicate that the MNSI is a good screening tool for
      diabetic neuropathy and that the MDNS coupled with nerve conductions provides a
      simple means to confirm this diagnosis.

PMID- 7821169
TI  - Impact of obesity on neuropathic late complications in NIDDM.
AB  - OBJECTIVE: This cross-sectional study was aimed to investigate the isolated
      influence of obesity on peripheral sensorimotor and autonomic neuropathy in
      patients with long-term non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH
      DESIGN AND METHODS: Ninety-one long-term NIDDM patients with a mean duration of
      13.6 +/- 1.0 years and a mean age of 60.4 +/- 1.0 years were divided into two
      groups according to their body mass index (BMI) (lean with a BMI < 26.5: n = 41,
      age = 58.6 +/- 1.7 years, BMI = 23.7 +/- 0.3 kg/m2; and obese with a BMI > or =
      26.5: n = 50, age = 61.9 +/- 1.2 years, BMI = 30.5 +/- 0.5 kg/m2). The two groups
      were not different in age, duration, gender, current parameters of glycemic
      control, number of smokers, cholesterol, triglycerides, and systolic and
      diastolic blood pressure. Neuropathic late complications were scrutinized by a
      standardized clinical examination that delivers a neuropathy score, pupillary
      autonomic neuropathy assessed by pupillometry, and cardiovascular autonomic
      neuropathy using a standardized test battery. RESULTS: One-way analysis of
      variance revealed that obese patients had poor results in the clinical neuropathy
      test (overall score in obese vs. lean: 71.1 +/- 2.9 vs. 80.6 +/- 3.0 points, 2P =
      0.0266; 100 points were absolutely normal). This was particularly true for the
      discrimination perception (obese vs. lean: 67.0 +/- 4.0 vs. 81.7 +/- 3.3 points,
      2P = 0.0073) and the reflex status (obese vs. lean: 57.4 +/- 4.0 vs. 71.8 +/- 4.3
      points, 2P = 0.0164). Furthermore, obese patients had a poor result in the
      respiratory sinus arrhythmia (RSA) test, one of six autonomic function tests
      (RSA: obese vs. lean in average RSA percentile: 36.9 +/- 4.9 vs. 54.0 +/- 5.9%,
      2P = 0.0264). CONCLUSIONS: Obesity influences sensorimotor and autonomic
      neuropathic late complications. The poor result in RSA in obesity may indicate an
      interrelation between pathogenesis of obesity and disorders of the respiratory
      and heart rhythm-generating control centers in the brain stem. Moreover, it could
      be due to intrathoracic fat deposits that alter lung mobility. Body mass control
      may be an important approach to reduce neuropathic complications. Beyond that, it
      seems necessary to control for body mass when comparing neuropathy in two groups
      of patients with NIDDM.

PMID- 7821171
TI  - Comparison of pharmacokinetics and pharmacodynamics of short- and long-term
      glyburide therapy in NIDDM.
AB  - OBJECTIVE: To examine the pharmacokinetics and pharmacodynamics of glyburide
      after single- and multiple-dose administration in patients with type II diabetes.
      RESEARCH DESIGN AND METHODS: Twenty patients with type II diabetes between 40 and
      70 years of age participated in the study. A 24-h pharmacokinetic evaluation
      including a 4-h Sustacal tolerance test was conducted before instituting
      glyburide therapy (baseline), after the first 2.5-mg test dose of glyburide and
      at weeks 6 and 12 of chronic glyburide therapy. Glyburide doses were titrated
      with a target goal of achieving a fasting plasma glucose of < or = 7.8 mmol/l or
      to reach maximum daily doses of 20 mg. RESULTS: A significant prolongation in the
      elimination half-life (t1/2: week 0, 4.0 +/- 1.9 h; week 6, 13.7 +/- 10.5 h; and
      week 12, 12.1 +/- 8.2 h) and an increased volume of distribution of glyburide was
      observed during chronic dosing. These results strongly suggest possible drug
      accumulation. No differences in pharmacokinetic parameters were noted between
      evaluations at week 6 or week 12. Changes in pharmacodynamic response of glucose,
      insulin, and C-peptide to chronic glyburide therapy were observed. Glyburide
      therapy significantly reduced plasma glucose levels at weeks 6 and 12 (percent
      changes in AUC0-->4. glucose from baseline: week 0, -3 +/- 11%; week 6, -29 +/-
      13%; and week 12, -26 +/- 19%). Pancreatic insulin secretion was acutely enhanced
      and maintained during long-term therapy. Responsiveness to therapy as assessed by
      the ratio of AUC0-->4.glucose:AUC0-->4.C-peptide was significantly improved at
      all weeks compared with baseline. No pharmacodynamic response differences were
      observed between the week 6 and the week 12 evaluations. CONCLUSIONS: This study
      demonstrates that significant differences in glyburide pharmacokinetics and
      pharmacodynamics exist between single-dose and steady-state conditions. These
      differences support the need for careful dosage titration of glyburide to achieve
      a desired therapeutic response in patients with type II diabetes.

PMID- 7821170
TI  - Intraperitoneal insulin delivery decreases the levels of chylomicron remnants in
      patients with IDDM.
AB  - OBJECTIVE: To investigate whether intraperitoneal insulin (IPII) decreases the
      levels of circulating chylomicron remnants in patients with insulin-dependent
      diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS: Eight nonobese,
      normolipidemic IDDM patients were studied twice: before (while on subcutaneous
      insulin) and 6 months after initiation of IPII by a programmable implanted
      medication system. Fasting and mean blood glucose, HbA1, and lipid values were
      determined. Blood samples were also drawn before and every 2 h for 10 h after
      ingestion of a fat meal (corn oil + Vitamin A). Triglycerides (TGs),
      apolipoprotein B (apoB), and retinyl esters were determined over time in two TG
      rich lipoprotein subfractions (Sf > 100 and Sf20-100) isolated from plasma by
      density-gradient ultracentrifugation. RESULTS: IPII slightly decreased the mean
      blood glucose from 7.8 +/- 1.1 to 7.4 +/- 1.1 mmol/l (mean +/- SD, P = 0.027,
      paired Student's t test) and the HbA1 from 9.4 +/- 1.5 to 8.7 +/- 1.2 (NS). TG
      and apoB levels in postprandial Sf > 100 and Sf20-100 were not changed by IPII.
      On IPII, however, retinyl ester levels in Sf > 100 decreased (P = 0.05, analysis
      of variance [ANOVA]) and tended to be lower in Sf20-100 (P = 0.075). In addition,
      following IPII, the retinyl ester:apoB ratio was lower in Sf > 100 (P = 0.0002)
      and marginally lower (P = 0.06) in Sf 20-100. CONCLUSIONS: IPII decreased
      chylomicron remnant levels, which might decrease the atherosclerotic risk in
      IDDM. Since glycemic control was only slightly improved, the effect was most
      likely due to the intraperitoneal route of delivery.

PMID- 7821172
TI  - Hyperproinsulinemia of type II diabetes is not present before the development of
      hyperglycemia.
AB  - OBJECTIVE: To examine proinsulin and insulin levels in first-degree relatives of
      patients with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN
      AND METHODS: Comparison of insulin and proinsulin responses to an oral glucose
      tolerance test in four groups of individuals: 1) 31 patients with newly diagnosed
      NIDDM treated with diet alone, 2) 34 first-degree relatives of NIDDM patients
      with impaired glucose tolerance (IGT), 3) 26 relatives with normal glucose
      tolerance (NGT), and 4) 30 subjects without a family history of diabetes.
      RESULTS: Both fasting and post-glucose levels of proinsulin were elevated in
      patients with diabetes, but not in the relatives with IGT or NGT. Levels of true
      insulin were highest in the diabetic group, followed by the subjects with IGT,
      and were lowest among relatives with NGT. Proinsulin levels correlated with
      glucose levels, suggesting that hyperglycemia is the main stimulus for increased
      proinsulin secretion. CONCLUSIONS: First-degree relatives of NIDDM patients, who
      have a high risk of developing diabetes, do not exhibit elevated levels of
      fasting or glucose-stimulated proinsulin as long as their fasting glucose levels
      remain normal.

PMID- 7821174
TI  - Hospital use among diabetic patients and the general population.
AB  - OBJECTIVE: This register-based linkage study compared hospital use among diabetic
      and nondiabetic populations. The study focused on overall use, use by disease
      categories, and inpatient care caused by complications. RESEARCH DESIGN AND
      METHODS: The patient data were derived from the Hospital Discharge Register and
      the Central Drug Register in Finland. All drug-treated diabetic patients and
      discharges of patients in a 3-year period were included in the study. Hospital
      use was measured by inpatient days, mean length of stay, and discharge rate.
      RESULTS: Among diabetic patients were eligible for drug reimbursement, 14.2% had
      at least one hospital stay because of diabetes in a year, while 50.7% had at
      least one hospital stay for any cause. Only 12.4% of the nondiabetic population
      was hospitalized annually. Patients with diabetes as the principal diagnosis
      consumed about 3% of all inpatient days; patients who had diabetes either as the
      principal or as a subsidiary diagnosis used 8.3%; and people who were eligible
      for antidiabetic drug reimbursement used 13.3% of total inpatient days. Among
      diabetic children, the risk for hospitalization was 6.5 times higher than among
      nondiabetic children. With advancing age, causes other than diabetes increasingly
      dominated hospitalization among diabetic patients. Inpatient days because of
      cardiovascular diseases were 1.6-18 times more common among diabetic patients
      than among nondiabetic patients, depending on gender and age-group. Diabetic
      patients used many more hospital inpatient days than did the nondiabetic
      population for a number of other disease categories that are usually not related
      to diabetes. CONCLUSIONS: Hospital use among diabetic patients is substantially
      greater than that among the nondiabetic population, mainly because of
      cardiovascular and microvascular complications, but also because of diseases
      unrelated to diabetes.

PMID- 7821173
TI  - Impaired glucose tolerance and NIDDM: does a lifestyle intervention program have
      an effect?
AB  - OBJECTIVE: To determine whether a 2-year lifestyle intervention program improves
      glucose tolerance and lipid levels in people with persistent impaired glucose
      tolerance (IGT) or non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH
      DESIGN AND METHODS: Screening for IGT and NIDDM was carried out in 1,752 people.
      Subjects with persistent IGT or NIDDM completed three 2-h oral glucose tolerance
      tests (OGTTs) before the start of the study and after 2 years. A single OGTT was
      carried out every 3 months. A 4-day food diary and a 7-day exercise diary were
      completed, and weight, blood pressure, glycated hemoglobin (HbA1), plasma lipids,
      and fasting and 2-h serum insulin were measured at baseline and every 3 months.
      Subjects were encouraged to make dietary changes and increase exercise. RESULTS:
      Thirty-two subjects with persistent IGT and 20 subjects with NIDDM were
      recruited. Women reported significant decreases in total and saturated fat and an
      increase in carbohydrate, but few subjects reached the recommended intakes. Men
      achieved smaller dietary changes. There were significant decreases in body mass
      index, fasting and 2-h plasma glucose, HbA1, total cholesterol, low-density
      lipoprotein cholesterol, and triglyceride levels in both the IGT and NIDDM groups
      during the study. CONCLUSIONS: Results suggest that a diet and exercise program
      can result in significant improvements in a range of clinical and metabolic
      variables in some people with IGT or NIDDM, although the absence of a control
      group precludes firm conclusions. Screening for IGT in those at high risk for
      developing NIDDM and offering those with persistent IGT a lifestyle intervention
      program could help reduce the progression of IGT to NIDDM.

PMID- 7821175
TI  - Common carotid arterial wall thickness in NIDDM subjects.
AB  - OBJECTIVE: To verify whether carotid arterial intimal plus media thickness (IMT)
      is greater in non-insulin-dependent diabetes mellitus (NIDDM) subjects, known to
      be at high risk for atherosclerosis. Evidence is growing that IMT is increased in
      subjects with coronary heart disease (CHD) risk factors like hypercholesterolemia
      and cigarette smoking. RESEARCH DESIGN AND METHODS: Fifty-four NIDDM subjects and
      54 sex- and age-matched control subjects underwent CHD risk factors assessment
      and echo-Doppler examination of carotid arteries. IMT was measured by computer
      technique in the common carotid artery (CCA). Presence of plaques and/or stenosis
      (carotid atherosclerosis [CA]) was also evaluated by a single-blinded reader.
      RESULTS: NIDDM subjects had larger IMT, higher levels of triglycerides, and lower
      concentrations of high-density lipoprotein (HDL) cholesterol compared with
      control subjects. IMT was positively correlated to age and systolic blood
      pressure and inversely to HDL cholesterol in both groups. The prevalence of CA
      was 46% in NIDDM subjects and 18% in control subjects. In multiple regression
      analysis, IMT was the only variable significantly associated to CA. CONCLUSIONS:
      IMT of CCA is enlarged in NIDDM subjects compared with control subjects. Its
      association with carotid plaques and/or stenosis might be of importance to detect
      early atherosclerotic lesions in the carotid arteries.

PMID- 7821176
TI  - Prevalence of adult-onset IDDM in the U.S. population.
AB  - OBJECTIVE: To investigate the prevalence of adult-onset insulin-dependent
      diabetes mellitus (IDDM) in a nationally representative sample of adults 30-74
      years of age. Although it is a widely held belief that onset of IDDM in adults is
      rare, there are few objective data to support this. Adult-onset IDDM may
      represent a disease that is biologically distinct from youth-onset IDDM, and it
      would be important to distinguish these two entities. RESEARCH DESIGN AND
      METHODS: The Second National Health and Nutrition Examination Survey (NHANES II)
      contained a national probability sample of 12,102 subjects 30-74 years of age in
      the U.S. population. All subjects with diabetes diagnosed by a physician before
      the survey were identified. Cases of IDDM defined by age at diagnosis > or = 30
      years, continuous or nearly continuous insulin treatment since diagnosis of
      diabetes, and relative body weight < or = 125 were classified as adult-onset
      IDDM. RESULTS: Subjects with adult-onset IDDM represented 0.30% of the U.S.
      population 30-74 years of age and 7.4% of all diabetic patients diagnosed at 30
      74 years of age. CONCLUSIONS: These data indicate that onset of IDDM in adults is
      uncommon. Given the limitations of the survey instrument, subclinical or slowly
      progressive IDDM (as distinguished from non-insulin-dependent diabetes mellitus
      with progressive loss of beta-cell function) would not have been detected, and
      these would constitute additional cases of adult-onset IDDM. However, the data
      suggest that a very large population base would be required to identify
      sufficient numbers of adult-onset IDDM cases for study of the etiology and
      pathogenesis of this disease.

PMID- 7821177
TI  - Human leukocyte antigen class II polymorphisms and genetic susceptibility of IDDM
      in Egyptian children.
AB  - OBJECTIVE: To analyze the association between human leukocyte antigen (HLA) and
      insulin-dependent diabetes mellitus (IDDM) in the Egyptian population for the
      first time and, thus, to determine the frequency of risk-associated alleles
      identified by a genomic HLA class II typing. Egyptians are genetically classified
      as North Africans and considered to be between Caucasoids and Africans (closer to
      Caucasoids). RESEARCH DESIGN AND METHODS: HLA class II typing was performed for
      50 IDDM patients and 50 healthy control subjects by a restriction fragment-length
      polymorphism (RFLP) technique. The analysis of position 57 of the DQB1 molecules
      was conducted by polymerase chain reaction and specific sequence oligonucleotide
      hybridization. RESULTS: The frequency of DRB1*0301-DRB3*0201-DQA1*0501-DQB1*0201
      haplotype was 43.9% in the IDDM patients and 7.1% in the control subjects (P <
      0.00001), reflecting the increased prevalence of DQA1*0501 susceptibility allele
      coding for arginine (Arg) in position 52 and DQB1*0201 susceptibility allele non
      coding aspartic acid (Asp) at position 57. Alleles DQB1*0601 and 0603, both
      carrying Asp at position 57 of the beta-chain, and DQA1*0103, encoding a non-Arg
      52 alpha-chain, were significantly decreased among the IDDM patients. The
      presence of four susceptibility residues (two DQA1 Arg 52+ and two DQB1 Asp 57-)
      conferred the highest relative risk at 20.2. On the other hand, homozygous
      genotypes for DQA1 non-Arg 52 and DQB1 Asp 57 were found only in the control
      group. CONCLUSIONS: IDDM susceptibility and resistance in the Egyptian population
      is strongly associated with the expressed DQ alpha- and beta-heterodimers in a
      dose-effective manner, as already defined in many different ethnic groups.

PMID- 7821178
TI  - Cholesterol absorption and cholesterol and bile acid synthesis in two brothers
      with IDDM and diarrhea.
AB  - OBJECTIVE: To determine the best possible treatment for two brothers who had IDDM
      and bile acid malabsorption-associated disabling diarrhea that was resistant to
      cholestyramine, antibiotics, clonidine, loperamide, or anticholinergic drugs.
      RESEARCH DESIGN AND METHODS: Our study paired these two brothers with control
      subjects. Serum noncholesterol sterols and fecal elimination of cholesterol and
      plant sterols were quantitated by gas-liquid chromatography. RESULTS: Fecal
      losses of bile acids exceeded four to six times the control values, and
      cholesterol synthesis was increased two to three times. Cholesterol absorption
      efficiency and serum cholesterol concentrations were, respectively, within the
      high and low control range. CONCLUSIONS: Bile acid malabsorption might have
      resulted from deranged intestinal motility, possibly contributed by
      gastrointestinal neuropathy, and some genetic factor.

PMID- 7821180
TI  - A case of diabetic pregnancy controlled with a percutaneous access device for
      intraperitoneal insulin infusion.

PMID- 7821179
TI  - Rhinocerebral mucormycosis in IDDM. Sequential magnetic resonance imaging of long
      term survival with intensive therapy.
AB  - OBJECTIVE: To describe the clinical course and the utility of computerized
      tomography (CT) and magnetic resonance imaging (MRI) in the successful management
      of an often fatal fungal infection in a 12-year-old patient with insulin
      dependent diabetes mellitus (IDDM). CASE: The patient was admitted to The
      University of Mississippi Medical Center (UMC) for the purpose of diabetic
      ketoacidosis (DKA) management and subsequent intensive therapy for mucormycosis
      according to nationally accepted standards of care. Strict diabetic control was
      instituted with frequent monitoring of blood glucose levels and interval
      assessment of HbA1c. Sequential MRI studies were obtained according to approved
      patient standards; the clinical and MRI course of the infection was charted.
      RESULTS: The patient's DKA resolved within 12 h on intravenous fluid repletion
      and insulin therapy. His sinusitis/rhinitis noted on admission did not respond to
      intravenous antibiotic therapy and progressed with obvious left orbital
      involvement and left cranial nerve palsies by 72 h of hospitalization. CT and MRI
      were invaluable aids to the early diagnosis and design of appropriate surgical
      and antifungal management of this patient, who survived with minimal left cranial
      nerve palsies. CONCLUSIONS: Our patient is among the youngest of IDDM patients
      reported to have survived rhinocerebral mucormycosis. His survival is attributed
      to early recognition of possible mucormycosis with diagnostic support of CT and
      MRI, surgical debridement and antifungal therapy, and intensive blood glucose
      control. Sequential MRI is invaluable to the design of therapy for this type of
      patient and shows the nearly 3-year recovery from mucormycosis.

PMID- 7821181
TI  - Licorice ameliorates postural hypotension caused by diabetic autonomic
      neuropathy.

PMID- 7821182
TI  - Consensus development conference on the diagnosis and management of nephropathy
      in patients with diabetes mellitus. American Diabetes Association and the
      National Kidney Foundation.

PMID- 7821183
TI  - Diuretic treatment of hypertension in diabetes.

PMID- 7821184
TI  - Interference of dapsone in HbA1c monitoring of a type I diabetic patient with
      necrobiosis lipoidica.

PMID- 7821185
TI  - IDDM and epidemics.

PMID- 7821186
TI  - Lipoprotein(a) and silent myocardial ischemia in IDDM.

PMID- 7821187
TI  - Reliability of driving performance during moderate hypoglycemia in adults with
      IDDM.

PMID- 7821188
TI  - American Diabetes Association meetings, 1994. Complications of diabetes mellitus.

PMID- 7821189
TI  - Preserved left ventricular systolic and diastolic function in normoalbuminuric
      insulin-dependent diabetic patients with glomerular hyperfiltration.
AB  - This study was conducted to test the hypothesis that normotensive,
      normoalbuminuric IDDM patients with glomerular hyperfiltration may present
      functional or structural cardiac abnormalities. Eleven normoalbuminuric and
      normotensive IDDM patients with normal glomerular filtration rate and 11 patients
      with hyperfiltration were compared with a group of 17 age and sex matched
      controls. Glomerular filtration rate was measured by the 51Cr-EDTA technique and
      hyperfiltration was defined as a glomerular filtration rate higher than 134
      ml/min/1.73 m2. Phonocardiogram, M-mode and pulsed Doppler two-dimensional
      echocardiograms were performed to evaluate resting left ventricular dimensions,
      systolic and diastolic function. Left ventricular dimensions, fractional
      shortening, mean velocity of fiber shortening, early and late diastolic peak
      filling velocity, deceleration time, mitral flow velocity integral, and
      isovolumic relaxation time were similar (ANOVA P > 0.05) in normal controls,
      diabetic patients with normal glomerular filtration rate, and diabetic patients
      with hyperfiltration. In conclusion, the results of our controlled observations
      indicate that normoalbuminuric and normotensive IDDM patients who have normal
      glomerular filtration rate or hyperfiltration have no Doppler-echocardiographic
      evidence of functional and structural abnormalities.

PMID- 7821190
TI  - Influence of intensified insulin regimen on quality of life and metabolic control
      in insulin-dependent diabetes mellitus.
AB  - Seventy-eight non-randomized patients with IDDM, aged 33.8 +/- 9.6 years (mean +/
      S.D.), with a duration of diabetes of 16.6 +/- 9.5 years and a HbA1c level of
      8.0% +/- 1.5 at baseline were included in the study. The effects of a change from
      a 3-dose insulin regimen using conventional syringes to a treatment mode using 4
      injections per day with a pen injector on metabolic control, perceived distress
      from diabetes on everyday life and correspondence between expectations and
      experiences of treatment during a 1-year trial were assessed. The experience
      measures were registered at baseline and after 3 and 12 months, respectively.
      HbA1c levels were measured every 3 months. Neither the metabolic control nor the
      body mass index or rate of hypoglycemic episodes changed during the study period.
      However, the patients experienced a decreased distress from diabetes, which
      appeared during the first 3 months and remained unchanged thereafter. The
      expectations of advantages from the intensified insulin therapy were generally
      high and were mostly either fulfilled or exceeded by experiences. We conclude
      that multiple insulin injection therapy, under routine treatment conditions, is
      subjectively preferable to patients and has favourable effects on their quality
      of life although something more is required in order to also achieve an
      improvement of metabolic control.

PMID- 7821191
TI  - Galactosemia produces ARI-preventable nodal changes similar to those of diabetic
      neuropathy.
AB  - The present study was designed to examine the development of structural changes,
      characteristic of diabetic neuropathy, in chronic galactosemia and their
      responsiveness to inhibition of the polyol-pathway. Sprague-Dawley rats weighing
      70-90 g were given a 50% galactose diet continued for 4 or 8 months. Half of
      these animals were simultaneously given the aldose reductase inhibitor (ARI) WAY
      121-509. ARI-treatment normalized galactitol and myoinositol levels in the
      sciatic nerve. At 4 months, sciatic nerve conduction velocity (NCV) in
      galactosemic rats was reduced by 30% which was prevented in ARI-treated rats. At
      8 months galactosemia reduced NCV to 58% of control values, while ARI-treatment
      for 8 months improved NCV to 71% of control values. ARI-treatment prevented in
      galactosemic rats nodal structural changes characteristic of diabetic neuropathy,
      whereas axonal atrophy was not affected by ARI-treatment, which may in part
      account for the only partial prevention of the NCV slowing at 8 months. Nerve
      fiber regeneration was increased 4-fold in ARI-treated rats compared with
      untreated galactosemic rats. These data suggest that chronic galactosemia
      produces a neuropathy structurally similar to diabetic neuropathy. The lack of an
      ARI-treatment effect on axonal atrophy suggests that this defect is not polyol
      related in galactosemia.

PMID- 7821193
TI  - Fibrocalculous pancreatic diabetes in infancy--two case reports.
AB  - Fibrocalculous pancreatic diabetes (FCPD) is a form of diabetes secondary to
      tropical calcific pancreatitis (TCP). The usual age of onset of FCPD is between
      15 and 50 years. This paper reports on two unusual cases of FCPD with age of
      onset below 5 years. This is the first report of FCPD in infancy and raises
      intriguing questions about the rapidity with which calcification occurs in this
      entity.

PMID- 7821192
TI  - Retrograde versus antegrade cannulation in the intravenous glucose tolerance
      test.
AB  - To investigate whether drawing blood from a retrogradely cannulated hand vein
      rather than an antegradely cannulated arm vein improves reproducibility in the
      intravenous tolerance test (IVGTT) we compared these two methods directly by
      drawing blood from the two sites on the same arm simultaneously. We found no
      difference in intrasubject coefficients of variation for the measurement of
      insulin response to glucose (21.5% vs. 22.5%) or insulin sensitivity (22.8 vs.
      24.7%) for these two methods. However, the values for insulin response to glucose
      were significantly increased when blood was drawn from the hand site (410.1 vs.
      328.7 pM, P < 0.05). In addition, the failure rate for studies using the
      retrogradely cannulated hand vein was significantly increased (5% of arm veins
      vs. 20% of hand veins cannulated, P < 0.05) particularly in female subjects. In
      conclusion, drawing blood samples from a retrogradely cannulated hand vein
      appears to have no effect on the reproducibility of the intravenous glucose
      tolerance test. The acute insulin response to glucose obtained from samples drawn
      in this manner is, however, significantly increased and this should be borne in
      mind when comparing results from centers using these different methods.

PMID- 7821194
TI  - Effects of diazoxide on alpha- and beta-cell function in isolated perfused rat
      pancreas.
AB  - To elucidate the effects of diazoxide on insulin and glucagon secretion at
      normal, high and low glucose concentrations and 10 mmol/l arginine, we performed
      pancreatic perfusion experiments. The insulin secretion rate in response to 16.7
      mmol/l glucose was dose-dependently suppressed by concomitant infusion of
      diazoxide (100 and 300 mumol/l). Both the first and second phases of glucose
      stimulated insulin secretion were significantly reduced in the presence of
      diazoxide as compared with controls. Basal glucagon secretion rate at 5.6 mmol/l
      glucose was significantly reduced by the administration of both 100 and 300
      mumol/l diazoxide. Furthermore, the glucagon secretion rate at a high glucose
      concentration (16.7 mmol/l) was significantly lower with 300 mumol/l diazoxide
      than in the control. The glucagon secretion rate with glucopenia (1.4 mmol/l) was
      also significantly lower with 100 and 300 mumol/l diazoxide than in the control.
      The insulin secretion rate in response to 10 mmol/l arginine was also dose
      dependently suppressed by concomitant infusion of diazoxide. The glucagon
      secretion rate in response to 10 mmol/l arginine was, however, significantly
      higher with 100 mumol/l diazoxide while not being significantly different with
      300 mumol/l diazoxide. These findings suggest that some mechanism(s) which can be
      inhibited by diazoxide is involved in glucagon, as well as insulin, secretion in
      isolated perfused rat pancreas.

PMID- 7821195
TI  - Protective effect of heparin on renal glomerular anionic sites of streptozotocin
      injected rats.
AB  - Albuminuria at the rate of 500 micrograms/24 h was observed in rats treated with
      50 mg/kg body wt. i.v. streptozotocin (STZ). When STZ was combined with heparin,
      administered twice daily (250 IU/kg subcutaneous injection) after 24 h following
      STZ injection, the daily urinary albumin excretion (U-AE) was less than half the
      amount found in non-heparinized rats (280.3 micrograms/24 h). The observation
      period in both instances was 8 weeks. When animals were permitted to develop
      albuminuria over the first 4 weeks, subsequent heparin administration for another
      4 weeks lowered U-AE from 500 micrograms/24 h to less than half the amount (227.8
      micrograms/24 h). A significantly negative correlation (P < 0.001) existed
      between U-AE and the number of anionic sites (AS) in the lamina rara externa of
      glomerular basement membranes, as visualized by electron microscopy. The number
      of AS per 1000 nm in STZ-injected rats (15.5 +/- 0.2) was lower than that in
      control rats (23.1 +/- 0.6); however, in heparinized animals, regardless of STZ,
      the values were not significantly different from normal. Heparin by itself had no
      effect on the number of AS in normal rats. All STZ-injected animals became
      hyperglycemic (400-550 mg/dl), but received no insulin. Heparin had no effect on
      plasma glucose levels. From these results, it is concluded that heparin
      suppressed both of an increase in U-AE and a decrease in AS count of glomerular
      basement membranes in STZ-injected rats.

PMID- 7821196
TI  - Somatosensory evoked potentials in non-insulin-dependent diabetics with different
      degrees of neuropathy.
AB  - Changes in median nerve somatosensory evoked potential (SEP) in diabetic patients
      have amply been reported. However the relationships between the diabetic
      polyneuropathy and the abnormalities of SEPs are still a matter of discussion. To
      elucidate these relationships, we have studied SEPs in 38 non-insulin-dependent
      diabetics with mild or severe degree of peripheral neuropathy. Our principal
      findings are as follows. (i) The wrist-Erb point (EP) conduction velocity (WECV)
      and the EP-N13 interpeak latency are significantly altered in diabetics. The N11
      N13, N13-N20 and N13-P22, interpeak latencies are within the normal range. (ii)
      The WECV is more reduced in patients with severe neuropathy than in those with
      mild neuropathy, whereas the degrees of neuropathy have no influence on the
      alterations of EP-N13 interpeak latency. (iii) No significant correlation is
      found between the WECV and the EP-N13 interpeak latency. (iv) The WE conduction
      velocity was significantly correlated with both motor and sensory peripheral
      nerve conduction velocities. On the contrary, no correlation is found between
      these latter peripheral parameters and the EP-N13 interpeak latency. These
      findings indicate that the alteration in the tract from brachial plexus to the
      posterior column could not be a parallel process of distal neuropathy of non
      insulin-dependent diabetic patients.

PMID- 7821197
TI  - Elevated adenosine deaminase activity in the serum of patients with diabetes
      mellitus.
AB  - Adenosine deaminase (ADA) is suggested to be an important enzyme for modulating
      the bioactivity of insulin, but its clinical significance in diabetes mellitus
      (DM) is not yet characterized. We measured the serum levels of ADA isoenzymes
      (ADA1 and ADA2) in healthy donors (HD, n = 52), insulin-dependent diabetes
      mellitus (IDDM, n = 53) patients and non-insulin-dependent diabetes mellitus
      (NIDDM, n = 65) patients. The mean serum level of ADA1 in HD, IDDM or NIDDM
      patients was, respectively 6.5, 8.1 or 9.5 units/l (P < 0.001 vs. HD) and that of
      ADA2 in HD, IDDM or NIDDM patients was 7.0, 14.9 (P < 0.001 vs. HD) or 11.2
      units/l (P < 0.001 vs. HD), respectively. Normalization of the blood glucose
      level by the hospitalization was associated with the decrease in ADA2 (but not
      ADA1) activity in 6 of 8 IDDM or 11 of 12 NIDDM poorly controlled patients. ADA2
      (but not ADA1) activity in the poorly controlled NIDDM patients directly
      correlated with the hemoglobin A1c level (P < 0.002). Measurement of serum ADA2
      activity may be important to better understand the clinical aspects of both IDDM
      and NIDDM. The pathogenic role of elevated ADA activity in the sera of DM
      patients was addressed.

PMID- 7821198
TI  - [Immunopathogenesis of allergic bronchial asthma. Detection of activated CD25-CD4
      lymphocytes and release of cytokines in the bronchoalveolar space following
      segmental allergen challenge].
AB  - The aim of this study was to investigate the fundamental processes underlying the
      inflammatory response to allergen in mild non-symptomatic asthmatics, using a new
      model entailing endobronchial segmental provocation. Ten asymptomatic asthmatic
      volunteers (8 male, 2 female; mean age 28.2 [24-41] years) were challenged
      employing the segmental allergen provocation technique. 250 PNU in 5 ml 0.9% NaCl
      solution of either birch (n = 8) or grass (n = 2) pollen were instilled into one
      segment. As control, only the solvent was instilled into a segment of the
      contralateral lung. Bronchoalveolar lavage (BAL) with 100 ml prewarmed saline was
      performed 10 min and 18 h after allergen provocation. The cellular distribution
      and activation state in BAL fluid and peripheral blood was analysed by
      immunofluorescence and flow cytometry. The concentration of various cytokines was
      determined in the BAL fluid using ELISA and bioassays. In blood, segmental
      allergen provocation led to an increase both in numbers of neutrophils (3833
      cells/microliters vs 6830 cells/microliters; P < 0.005) and activated IL-2R
      expressing (CD25+) CD4+ T cells (3.6% vs 4.8% of all CD4+ lymphocytes; P < 0.05).
      No change was observed in eosinophils and other leukocytes and lymphocyte
      subsets. In contrast, a significant 30-fold increase in eosinophils (0.39 x 10(6)
      vs 11.5 x 10(6) cells/100 ml; P < 0.01) and a twofold increase in CD25+ CD4+ T
      cells (P < 0.05) were found in BAL samples 18 h after segmental allergen
      challenge, when compared to the control segment. Analysis of the cytokine profile
      revealed significantly increased levels of several cytokines. Allergen challenge
      of extrinsic asthmatic subjects causes differentiation of activated CD25+ CD4+
      lymphocytes which may contribute to the pathogenesis of the asthmatic
      inflammation through the release of various cytokines.

PMID- 7821199
TI  - [Postmortem diagnosis of tropical malaria].
AB  - Thirteen days after returning from a four week holiday in Kenya a 35-year-old man
      consulted his doctor complaining of feeling unwell. The doctor diagnosed
      influenza and gave him a sickness certificate for three days. Because the patient
      did not reappear at his workplace a search was made and he was found dead in his
      flat seven days after seeing his doctor. A medicolegal autopsy was performed two
      days after the estimated time of death. There was marked swelling of liver and
      spleen together with jaundice and "dirty grey" colouration of the viscera.
      Samples of heart blood and spleen puncture material were taken. Giemsa stained
      preparations (ordinary and thick blood smears) revealed numerous objects 1.2 to
      1.5 microns in size with indistinct reddish blue staining, some of them arranged
      in rosettes reminiscent of schizonts. A few of them contained pigment. In
      material from the spleen there were masses of blackish-brown pigment. The malaria
      immunofluorescence test performed on serum gave a weakly positive titre of 1:40.
      The findings were considered enough to support a diagnosis of fulminant
      falciparum malaria, and this was confirmed by histological changes in various
      organs, notably the typical capillary blockages in the brain. Because of the
      popularity of long-haul tourism, cases of imported malaria are increasingly
      frequent and, in view of the insidiously progressive course of the disease, it
      should always be considered in the differential diagnosis. In cases of
      unexplained death, if there is any suspicion of malaria, blood should always be
      taken for appropriate investigations, in addition to blocks for histological
      examination.

PMID- 7821200
TI  - [Disseminated extrapulmonary tuberculosis in idiopathic CD4-lymphocytopenia].
AB  - A previously healthy, now 42-year-old man suddenly fell ill with bouts of septic
      fever up to 39.5 degrees C, sweats and weight loss without any demonstrable organ
      involvement. Physical examination on hospitalization 3 weeks after onset of the
      illness was unremarkable. Blood sedimentation rate at one hour was 123 mm. There
      was also a moderate increase in gamma-GT and alkaline phosphatase. Routine
      bacteriological and serological tests failed to discover a causative
      microorganism. After imaging tests had provided first indication of splenic and
      hepatic involvement, biopsies of these two organs demonstrated disseminated
      epithelioid granulomas and Langhans giant cells. Staining and culturing of pelvic
      crest biopsy tissue showed evidence of Mycobacterium tuberculosis, but there was
      no evidence of pulmonary involvement. In addition to four-drug tuberculostatic
      treatment the patient was given glucocorticoids for several weeks to control the
      fever bouts. Persistent CD4+ T-lymphocytopenia was demonstrated as the cause of
      the entirely extrapulmonary tuberculosis in this HIV-negative patient. This is an
      only recently described and so far unexplained syndrome.

PMID- 7821202
TI  - [Paroxysmal nocturnal hemoglobinuria--an acquired genetic defect of the
      hematopoietic stem cells].

PMID- 7821201
TI  - [Multicenter prospective study of the current status of treatment for bleeding
      ulcer in Germany].
AB  - The current state of ulcer treatment in Germany was analysed in a prospective
      multi-centre study. It was based on 1139 consecutive patients admitted to the
      participating hospitals because of upper gastrointestinal bleeding. The source of
      the bleeding was identified by diagnostic endoscopy in 1075 patients (94%), from
      a gastric and/or duodenal ulcer in 546 of them (mean age 62 +/- 18 years). Using
      Forrest's classification, 4% of patients were in bleeding stage Ia, 17% in stage
      Ib, 16% stage IIa, 30% stage IIb and 33% stage III. An attempt to arrest bleeding
      through the endoscope was made in 233 patients (43%): more often with tissue
      preserving substances (epinephrine +/- NaCl in 36%, fibrin glue +/- epinephrine
      in 24%) than with tissue-damaging procedures (epinephrine + polidocanol +/- NaCl
      in 26%, epinephrine + thermocoagulation in 7%). Primary haemostasis was achieved
      in 219 patients (94%). There was a total of 66 recurrences of bleeding (12%), but
      the rate was 18% after endoscopic haemostasis. 64 patients (12%) required
      operative intervention, including initial emergency operations. Severe
      complications (infections, organic failure) occurred in 82 patients (16%). 114 of
      the 546 patients were in the high risk group (older than 60 years; high amount of
      bleeding). Their bleeding recurrence and mortality rates (27 and 22%,
      respectively) were significantly higher (P < 0.01) than those of the total group.
      Overall mortality rate was 11% (58 patients). The mortality rate depended on the
      severity of initial bleeding (26% for Forrest group Ia). After recurrent bleeding
      the mortality rate was 34% with conservative and 33% with operative treatment. 7%
      of all deaths were the direct result of bleeding. The following factors
      prognostically closely correlated with mortality rate: age of patient (P < 0.01);
      haemoglobin < 8 g/dl on admission (P < 0.05); initial severity of bleeding
      (Forrest group I; P < 0.05); and recurrence of bleeding (P < 0.001).

PMID- 7821203
TI  - [Pathophysiology of myocardial circulation. III. Preliminary results of ischemia
      using ischemia ("ischemic preconditioning")].

PMID- 7821204
TI  - [New infectious diseases caused by viruses. Current knowledge and preliminary
      information].

PMID- 7821205
TI  - [How selective are cardioselective beta-receptor blockers?].

PMID- 7821206
TI  - [Chronic fatigue syndrome. The necessity for an integrated, interdisciplinary
      approach].

PMID- 7821207
TI  - Wingless can bring about a mesoderm-to-ectoderm induction in Drosophila embryos.
AB  - By means of nuclear transplantations, we make mosaics in which largely wingless-
      embryos contain patches of wingless+ cells. In these genetic mosaics, using a
      standard assay for wingless function (the maintenance of engrailed expression),
      we uncover an induction across germ layers: Wingless made in the mesoderm can
      sustain engrailed expression in the ectoderm. This result makes clear that
      Wingless is expressed in the mesoderm until at least one hour after gastrulation
      and may function in this germ layer in the wild type.

PMID- 7821208
TI  - Cardiovascular development in the zebrafish. II. Endocardial progenitors are
      sequestered within the heart field.
AB  - We have examined the zebrafish embryo to ascertain the location of endocardial
      and myocardial progenitors prior to gastrulation, in an attempt to define the
      earliest stages of cardiac patterning. Currently there is uncertainty as to the
      spatial and lineage relationship of the progenitors for these two phenotypically
      distinct cell types that form the two concentric layers of the primitive heart
      tube. By single-cell injection and tracking, we distinguish a region in the early
      and midblastula which has the properties of a heart field, in that it defines a
      zone of cardiac progenitors within which there is a spatial gradient of
      propensity to generate heart cells, and which regulates, in the sense of adapting
      to the transplantation of pluripotential cells. This zone extends from the future
      ventral axis dorsally along the margin, with cardiogenic propensity tapering off
      laterally and dorsally. Myocardial progenitors are spread throughout this region,
      but endocardial precursors are restricted to the ventral marginal region. The
      cardiovascular progeny of the ventral cells include, in addition to endocardium
      and myocardium, cells in the endothelium and blood.

PMID- 7821209
TI  - Diaphanous is required for cytokinesis in Drosophila and shares domains of
      similarity with the products of the limb deformity gene.
AB  - We show that the Drosophila gene diaphanous is required for cytokinesis. Males
      homozygous for the dia1 mutation are sterile due to a defect in cytokinesis in
      the germline. Females trans-heterozygous for dia1 and a deficiency are sterile
      and lay eggs with defective eggshells; failure of cytokinesis is observed in the
      follicle cell layer. Null alleles are lethal. Death occurs at the onset of
      pupation due to the absence of imaginal discs. Mitotic figures in larval
      neuroblasts were found to be polyploid, apparently due to a defect in
      cytokinesis. The predicted 123 x 10(3) M(r) protein contains two domains shared
      by the formin proteins, encoded by the limb deformity gene in the mouse. These
      formin homology domains, which we have termed FH1 and FH2, are also found in
      Bni1p, the product of a Saccharomyces cerevisiae gene required for normal
      cytokinesis in diploid yeast cells.

PMID- 7821210
TI  - Ectopic induction and reorganization of Wnt-1 expression in quail/chick chimeras.
AB  - When grafted ectopically into the diencephalon of a chick host embryo, a portion
      of met-mesencephalon straddling the met-mesencephalic constriction has the
      capacity to induce En-2 expression in the surrounding host tissue. Subsequently,
      tectal and cerebellar structures, composed of both host and grafted cells, are
      reconstructed in this ectopic location at the expense of the host diencephalon.
      Previous experiments indicated that the induction of En-2 was correlated with Wnt
      1 expression within the graft. The aim of the present study was: (i) to determine
      whether Wnt-1 expression was spatially regulated within the graft, (ii) to
      investigate whether host Wnt-1-expressing cells were also involved in the ectopic
      met-mesencephalic development and, if so, (iii) to localize these Wnt-1-positive
      domains in relation to the patterning of the ectopically developing met
      mesencephalic territory. We studied the expression profile of Wnt-1, in relation
      with that of other positional markers, in quail/chick chimeras where various
      portions of met-mesencephalon had been grafted into the diencephalon. We found
      that Wnt-1 expression was reorganized within the graft, and that it was also
      induced in the host in contact with the graft. Moreover, these ectopic
      expressions of Wnt-1, in both the grafted and the surrounding host tissues, were
      organized in concert to form a continuous positive line at the host/graft
      junction, the location of which depended on the precise origin of the graft.
      Finally, we found that this line was frequently located at the limit between
      territories expressing different positional markers. We propose that Wnt-1
      expression is turned on at the junction between domains of different phenotypes,
      and may be used as a border to stabilize these adjacent differently committed
      territories.

PMID- 7821211
TI  - Apoptosis during macrophage-dependent ocular tissue remodelling.
AB  - We have characterized the nature and pattern of cell death during regression of
      the pupillary membrane, a developmentally transient capillary network found in
      the anterior chamber of the eye. This analysis has revealed that the cellular
      components of the pupillary membrane include vascular endothelial cells in an
      intricate network of fine capillaries as well as attendant macrophages. The
      capillaries are situated on the anterior surface of the lens and held in relative
      position by a cobweb-like meshwork of extracellular matrix fibres that regress
      along with the cellular components of this structure. Cell death during
      regression of the pupillary membrane is characteristic of apoptosis.
      Specifically, apoptotic bodies containing condensed chromatin can be observed in
      vascular endothelial cells and genomic DNA isolated from the pupillary membrane
      shows the nucleosomal fragmentation pattern typical of apoptotic cells. Using a
      method for labelling fragmented DNA in tissue preparations (TUNEL), we have
      assessed the overall pattern of apoptotic cell death during pupillary membrane
      regression. We find that apoptosis occurs either in single cells in healthy
      vessels or synchronously along the entire length of a capillary segment. Both
      morphological and TUNEL analysis indicate that capillary regression occurs from
      junction to junction one segment at a time. We propose a model to explain the
      pattern of capillary regression observed and conclude from these and previous
      experiments (Lang and Bishop (1993) Cell 74, 453-462), that during regression of
      the pupillary membrane, the macrophage elicits target cell death by inducing
      apoptosis.

PMID- 7821212
TI  - Strain-specific differences in mouse oocytes and their contributions to
      epigenetic inheritance.
AB  - Previous experiments revealed a strain-dependent effect of egg cytoplasm on the
      developmental potential of androgenetic (two paternal genomes) mouse embryos.
      Eggs obtained from C57BL/6 mice supported androgenone development to the
      blastocyst stage at a much higher frequency than eggs from DBA/2 mice. Transient
      exposure of paternal pronuclei to DBA/2 egg cytoplasm also compromised
      development, indicating that the DBA/2 egg cytoplasm negatively affected the
      ability of paternal pronuclei to support blastocyst formation. An essential first
      step toward understanding the molecular mechanism by which egg modifier factors
      influence gene expression is to determine the number of loci that are responsible
      for the strain difference. To do this, (B6D2)F1 hybrid females were backcrossed
      to DBA/2 males and the eggs from individual female progeny assayed for their
      ability to support androgenetic development. Approximately one fourth of the
      backcross females produced eggs that failed to support androgenone development,
      indicating that two independently segregating genetic loci are most likely
      responsible for the difference between DBA/2 and C57BL/6 egg phenotypes.
      Comparison of DBA/2 and C57BL/6 oocytes by two-dimensional protein gel
      electrophoresis revealed at least 17 proteins that exhibited significant,
      reproducible, quantitative differences in rates of synthesis. All of these
      proteins were synthesized in (B6D2)F1 oocytes. These data, combined with the
      previous observation that the C57BL/6 egg phenotype is dominant, are consistent
      with a model in which a C57BL/6 allele at either locus provides a protective
      function, either by antagonizing the actions of the DBA/2 alleles or by
      providing, through partial or complete redundancy, a function not provided by the
      DBA/2 alleles.

PMID- 7821213
TI  - Sequential fates in a single cell are established by the neurogenic cascade in
      the Malpighian tubules of Drosophila.
AB  - In each Malpighian tubule of Drosophila, one cell is singled out, the tip cell,
      whose function during embryogenesis is to promote cell division in its
      neighbours. We follow the segregation of this cell, explore the genetic
      interactions that underlie its specification and demonstrate that tip cell
      allocation closely resembles neurogenesis. The tip cell arises by division of a
      tip mother cell, which is selected from a cluster of equivalent cells in each
      tubule primordium. Each cluster is marked out by the expression of proneural
      genes and the selection of a single cell from each group involves lateral
      inhibition, mediated by the neurogenic genes. We confirm the mitogenic role of
      the tip cell during embryogenesis by mutational analysis and show that it
      subsequently adopts a second fate, differentiating neural characteristics. We
      demonstrate that both stages in the differentiation of this cell are established
      by the same sequence of genetic interactions, which have not previously been
      shown to occur outside the neurogenic ectoderm.

PMID- 7821214
TI  - TGF-beta 1 influences the relative development of the exocrine and endocrine
      pancreas in vitro.
AB  - Pancreatic rudiments from E12.5 mouse embryos undergo extensive development and
      differentiation when cultured in three-dimensional gels of extracellular matrix
      proteins for up to 12 days. Whereas collagen gels promote the formation of
      numerous exocrine acini and relatively small clusters of endocrine cells, in
      basement membrane (EHS) matrices the development of endocrine cells is
      dramatically favoured over that of acinar tissue. Buds embedded in a collagen gel
      contiguous to an EHS gel also fail to develop acini, suggesting the involvement
      of diffusible factor(s). Addition of cytokines to cultures of pancreatic buds in
      collagen gels modifies the relative proportions of the epithelial components of
      the gland. In the presence of EGF the proportion of the tissue occupied by ducts
      overrides that of acinar structures, whereas the endocrine portion of the tissue
      is not significantly modified. TGF-beta 1 partially mimicks the effect of EHS
      matrix in inhibiting the development of acinar tissue without decreasing the
      amount of ducts and mesenchyme; TGF-beta 1 also promotes the development of
      endocrine cells, in particular of insulin-containing beta cells and of cells
      expressing genes of the PP-fold family. These results show that cytokines can
      modulate the development of the pancreas and suggest a role for TGF-beta 1 in
      regulating the balance between the acinar and endocrine portions of the gland in
      vivo. More generally, they are compatible with the notion that, during
      organogenesis, cytokines act as paracrine factors responsible for the development
      and maintenance of appropriate proportions of different tissue constituents.

PMID- 7821215
TI  - dachshund encodes a nuclear protein required for normal eye and leg development
      in Drosophila.
AB  - Neural specification and differentiation in the Drosophila eye sweep across the
      unpatterned epithelial monolayer of the eye imaginal disc following a
      developmental wave termed the morphogenetic furrow. The furrow begins at the
      posterior margin of the eye imaginal disc and moves anteriorly as a linear front.
      Progression of the furrow requires the function of hedgehog, which encodes a
      secreted signaling protein. We characterize mutations in dachshund, a gene that
      encodes a novel nuclear protein required for normal cell-fate determination of
      imaginal disc cells. In the absence of dachshund function, cells at the posterior
      margin of the eye disc fail to follow a retinal differentiation pathway and
      appear to adopt a cuticle fate instead. These cells are therefore unable to
      respond to pattern propagation signals such as hedgehog and furrow initiation
      does not occur. In contrast, cells in more anterior portions of the eye disc are
      able to differentiate as retinal cells in the absence of dachshund activity and
      respond normally to patterning signals. These results suggest that posterior
      margin cells are distinct from other cells of the eye imaginal disc by early
      stages of development. dachshund is also necessary for proper differentiation of
      a subset of segments in the developing leg. Null mutations in dachshund result in
      flies with no eyes and shortened legs.

PMID- 7821216
TI  - Mesenchymal regulation of epithelial gene expression in developing avian stomach:
      5'-flanking region of pepsinogen gene can mediate mesenchymal influence on its
      expression.
AB  - The expression of a gene encoding an embryonic chick pepsinogen was investigated
      in developing avian gut. Expression is restricted to the epithelial layer of the
      embryonic proventriculus (glandular stomach). We can therefore regard this gene
      as a marker gene for proventricular epithelial differentiation. There is some
      considerable evidence in favour of epithelial-mesenchymal interactions being
      important during the development of the gastrointestinal system; for example,
      pepsinogen expression is induced in proventricular and gizzard (muscular stomach)
      epithelial by the proventricular mesenchyme but is suppressed by the gizzard
      mesenchyme. In the present paper, we studied how the mesenchymes influence this
      gene expression pattern. For this we produced constructs containing various
      portions of the 5'-flanking region of the embryonic chick pepsinogen gene,
      driving reporter sequences (beta-galactocidase or luciferase), and these
      constructs were transfected into dissociated epithelial cells either from the
      proventriculus or gizzard. We then recombined these cells with mesenchymal cells
      and cultured them as cell aggregates. In this way, we were able to dissect the
      timing and other requirements of the epithelial-mesenchymal interactions for
      expression of embryonic chick pepsinogen gene. We also report that 1.1 kb of 5'
      flanking sequence is sufficient to drive correct expression of embryonic chick
      pepsinogen gene, although further enhancement was seen if the constructs
      contained 3.2 kb of upstream sequence.

PMID- 7821217
TI  - A developmental analysis of oligodendroglial integrins in primary cells: changes
      in alpha v-associated beta subunits during differentiation.
AB  - We have examined the expression of integrins on primary oligodendroglial cells
      during the differentiation of the proliferative oligodendrocyte precursor (O-2A
      progenitor) cell to the postmitotic oligodendrocyte. Cells of the oligodendrocyte
      lineage expressed a limited repertoire of integrins: alpha 6 beta 1 and alpha v
      integrins including alpha v beta 1, alpha v beta 3 and alpha v beta 5, as well as
      a potentially novel integrin alpha v beta 80 kDa. Integrin expression was
      developmentally regulated; during differentiation alpha v beta 1 was reduced and
      alpha v beta 5 upregulated. These results suggest that laminin and vitronectin
      are important extracellular matrix ligands for oligodendrocytes, and provide a
      rational explanation for previous observations that RGD peptides inhibit the
      expression of myelin-specific genes. They also suggest a simple model by which
      switching of integrin beta subunits might regulate differentiation. As chimeric
      beta 1 integrins with a beta 5 cytoplasmic domain support proliferation less well
      than normal beta 1 integrins (Pasqualini and Hemler (1994), J. Cell Biol. 125,
      447-460) the switch from alpha v beta 1 to alpha v beta 5 might play a key
      instructive role in the cessation of proliferation and subsequent
      differentiation.

PMID- 7821218
TI  - Spatiotemporal dynamics of intracellular [Ca2+]i oscillations during the growth
      and meiotic maturation of mouse oocytes.
AB  - Calcium oscillations occur during meiotic maturation of mouse oocytes. They also
      trigger activation at fertilization. We have monitored [Ca2+]i in oocytes at
      different stages of growth and maturation to examine how the calcium release
      mechanisms alter during oogenesis. Spontaneous calcium oscillations occur every 2
      3 minutes in the majority of fully grown (but immature) mouse oocytes released
      from antral follicles and resuming meiosis. The oscillations last for 2-4 hours
      after release from the follicle and take the form of global synchronous [Ca2+]i
      increases throughout the cell. Rapid image acquisition or cooling the bath
      temperature from 28 degrees C to 16 degrees C did not reveal any wave-like
      spatial heterogeneity in the [Ca2+]i signal. Calcium appears to reach highest
      levels in the germinal vesicle but this apparent difference of [Ca2+] in nucleus
      and cytoplasm is an artifact of dye loading. Smaller, growing immature oocytes
      are less competent: about 40% are able to resume meiosis and a similar proportion
      of these oocytes show spontaneous calcium oscillations. [Ca2+]i transients are
      not seen in oocytes that do not resume meiosis spontaneously in vitro.
      Nonetheless, these oocytes are capable of [Ca2+]i oscillations since they show
      them in response to the addition of carbachol or thimerosal. To examine how the
      properties of calcium release change during meiotic maturation, a calcium
      releasing factor from sperm was microinjected into fully grown immature and
      mature oocytes. The sperm-factor-induced oscillations were about two-fold larger
      and longer in mature oocytes compared to immature oocytes. Calcium waves
      travelling at 40-60 microns/second were generated in mature oocytes, but not in
      immature oocytes. In some mature oocytes, successive calcium waves had different
      sites of origin. The modifications in the size and spatial organization of
      calcium transients during oocyte maturation may be a necessary prerequisite for
      normal fertilization.

PMID- 7821219
TI  - FGF2 regulates proliferation of neural crest cells, with subsequent neuronal
      differentiation regulated by LIF or related factors.
AB  - Two of the key early events in the development of the peripheral nervous system
      are the proliferation of neural crest precursor cells and their subsequent
      differentiation into different neural cell types. We present evidence that
      members of the fibroblast growth factor family, (FGF1 or FGF2) act directly on
      the neural crest cells in vitro to stimulate proliferation in the presence of
      serum. These findings correlate with in situ hybridisation analysis, which shows
      FGF2 mRNA is expressed in cells both in the neural tube and within newly formed
      sensory ganglia (dorsal root ganglia, DRG) at embryonic day 10 in the mouse, when
      neural crest precursors are proliferating within the DRG. This data infers an
      autocrine/paracrine loop for FGF regulation of proliferation. Evidence supporting
      this notion is provided by the finding that part of the endogenous proliferative
      activity in the NC cultures is related to FGF. It was also found, in early neural
      crest cultures, that exogenous FGF completely inhibited neuronal differentiation,
      probably as a direct consequence of its mitogenic activity. In order to stimulate
      neuronal differentiation significantly, it was necessary to remove the FGF and
      replace it with leukemia inhibitory factor (LIF) or related factors. Under these
      conditions, 50% of the cells differentiated into neurons, which developed a
      sensory neuron morphology and were immunoreactive for the sensory markers CGRP
      and substance P. These data support a model of neural crest development, whereby
      multipotential neural crest precursor cells are stimulated to divide by FGF and
      subsequent development into sensory neurons is regulated by LIF or other
      cytokines with a similar signalling mechanism.

PMID- 7821220
TI  - The Notch signalling pathway is required for Enhancer of split bHLH protein
      expression during neurogenesis in the Drosophila embryo.
AB  - The Enhancer of split locus is required during many cell-fate decisions in
      Drosophila, including the segregation of neural precursors in the embryo. We have
      generated monoclonal antibodies that recognise some of the basic helix-loop-helix
      proteins encoded by the Enhancer of split locus and have used them to examine
      expression of Enhancer of split proteins during neurogenesis. The proteins are
      expressed in a dynamic pattern in the ventral neurogenic region and are confined
      to those ectodermal cells that surround a neuroblast in the process of
      delaminating. There is no staining in the neuroblasts themselves. We have also
      examined the relationship between Enhancer of split protein accumulation and the
      Notch signalling pathway. Protein expression is abolished in a number of
      neurogenic mutant backgrounds, including Notch, but is increased as a result of
      expressing a constitutively active Notch product. We conclude that Notch
      signalling activity is directly responsible for the accumulation of basic helix
      loop-helix proteins encoded by the Enhancer of split locus.

PMID- 7821221
TI  - Regulatory role of the G alpha 1 subunit in controlling cellular morphogenesis in
      Dictyostelium.
AB  - To determine the function of the Dictyostelium G alpha 1 subunit during
      aggregation and multicellular development, we analyzed the phenotypes of g alpha
      1 null cells and strains overexpressing either wild-type G alpha 1 or two
      putative constitutively active mutations of G alpha 1. Strains overexpressing the
      wild-type or mutant G alpha 1 proteins showed very abnormal culmination with an
      aberrant stalk differentiation. The similarity of the phenotypes between G alpha
      1 overexpression and expression of a putative constitutively active G alpha 1
      subunit suggests that these phenotypes are due to increased G alpha 1 activity
      rather than resulting from a non-specific interference of other pathways. In
      contrast, g alpha 1 null strains showed normal morphogenesis except that the
      stalks were thinner and longer than those of wild-type culminants. Analysis of
      cell-type-specific gene expression using lacZ reporter constructs indicated that
      strains overexpressing G alpha 1 show a loss of ecmB expression in the central
      core of anterior prestalk AB cells. However, expression of ecmB in anterior-like
      cells and the expression of prestalk A-specific gene ecmA and the prespore
      specific gene SP60/cotC appeared normal. Using a G alpha 1/lacZ reporter
      construct, we show that G alpha 1 expression is cell-type-specific during the
      multicellular stages, with a pattern of expression similar to ecmB, being
      preferentially expressed in the anterior prestalk AB cells and anterior-like
      cells. The developmental and molecular phenotypes of G alpha 1 overexpression and
      the cell-type-specific expression of G alpha 1 suggest that G alpha 1-mediated
      signaling pathways play an essential role in regulating multicellular development
      by controlling prestalk morphogenesis, possibly by acting as a negative regulator
      of prestalk AB cell differentiation. During the aggregation phase of development,
      g alpha 1 null cells display a delayed peak in cAMP-stimulated accumulation of
      cGMP compared to wild-type cells, while G alpha 1 overexpressors and dominant
      activating mutants show parallel kinetics of activation but decreased levels of
      cGMP accumulation compared to that seen in wild-type cells. These data suggest
      that G alpha 1 plays a role in the regulation of the activation and/or adaptation
      of the guanylyl cyclase pathway. In contrast, the activation of adenylyl cyclase,
      another pathway activated by cAMP stimulation, was unaffected in g alpha 1 null
      cells and cell lines overexpressing wild-type G alpha 1 or the G alpha 1 (Q206L)
      putative dominant activating mutation.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7821222
TI  - Control of CNS midline transcription by asymmetric E-box-like elements:
      similarity to xenobiotic responsive regulation.
AB  - Central nervous system midline cells constitute a discrete group of Drosophila
      embryonic cells with numerous functional and developmental roles. Corresponding
      to their separate identity, the midline cells display patterns of gene expression
      distinct from the lateral central nervous system. A conserved 5 base pair
      sequence (ACGTG) was identified in central nervous system midline transcriptional
      enhancers of three genes. Germ-line transformation experiments indicate that this
      motif forms the core of an element required for central nervous system midline
      transcription. The central nervous system midline element is related to the
      mammalian xenobiotic response element, which regulates transcription of genes
      that metabolize aromatic hydrocarbons. These data suggest a model whereby related
      basic-helix-loop-helix-PAS proteins interact with asymmetric E-box-like target
      sequences to control these disparate processes.

PMID- 7821223
TI  - Hypoblastic tissue and fibroblast growth factor induce blood tissue (haemoglobin)
      in the early chick embryo.
AB  - We have investigated the temporal and the causal basis of blood tissue
      specification in the chick embryo. Earlier workers have shown that the
      prospective blood-forming area is specified in a horseshoe-shaped area at the
      posterior side of the embryo. We found that cultured explants from the posterior
      marginal zone at stages XI to XIII (consisting of the posterior marginal zone and
      part of Koller's sickle) have a high propensity to form haemoglobin (Hb), which
      could be inhibited at stage XI by adding antibody against basic fibroblast growth
      factor (bFGF) to the neutral culture medium; this treatment had no effect from
      stage XII onwards. The same result was found when whole embryos were cultured
      with an antiserum raised against bFGF, or with heparin. In another series of
      experiments, we found that cultured pieces from the inner-core of stage XIII
      epiblasts (with or without hypoblast tissue) were able to form Hb, whereas inner
      core pieces from the pre-hypoblast stages, namely stages X and XI, did not form
      Hb. The capacity to form Hb, however, could be conferred upon the inner-core
      pieces from stage X epiblasts if bFGF at a concentration of 75-150 ng/ml was
      added to the culture medium. Furthermore, and most pertinently, the capacity to
      form Hb could be conferred on stage X inner-core pieces when they were co
      cultured with hypoblast from a stage XIII embryo in a sandwich explant. Thus the
      inductive role of the hypoblast appears to be mediated via bFGF.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7821224
TI  - The novel homeodomain gene buttonless specifies differentiation and axonal
      guidance functions of Drosophila dorsal median cells.
AB  - We have identified a novel homeodomain gene, buttonless (btn), that is
      specifically expressed in 20 cells of a single type during Drosophila embryonic
      development. These cells, the dorsal median (DM) cells, are arranged as a single
      pair within each segment along the dorsal midline of the CNS. Distinctive
      features of the DM cells include a large cell body and a long thick process
      extending laterally to the muscle attachment site. In the absence of btn gene
      function the initial commitment to the DM cell fate is made but differentiation
      fails to occur and the DM cells are lost. The btn mutation thus specifically
      eliminates the DM cells, and this genetic ablation in turn reveals a requirement
      for DM cells as cellular cues for axonal guidance during transverse nerve
      outgrowth and bifurcation of the median nerve.

PMID- 7821225
TI  - Regulation of scute function by extramacrochaete in vitro and in vivo.
AB  - The pattern of adult sensilla in Drosophila is established by the dosage
      sensitive interaction of two antagonistic groups of genes. Sensilla development
      is promoted by members of the achaete-scute complex and the daughterless gene
      whereas it is suppressed by whereas extramacrochaete (emc) and hairy. All these
      genes encode helix-loop-helix proteins. The products of the achaete-scute complex
      and daughterless interact to form heterodimers able to activate transcription. In
      this report, we show that (1) extra-macrochaete forms heterodimers with the
      achaete, scute, lethal of scute and daughterless products; (2) extramacrochaete
      inhibits DNA-binding of Achaete, Scute and Lethal of Scute/Daughterless
      heterodimers and Daughterless homodimers and (3) extramacrochaete inhibits
      transcription activation by heterodimers in a yeast assay system. In addition, we
      have studied the expression patterns of scute in wild-type and extramacrochaete
      mutant imaginal discs. Expression of scute RNA during imaginal development occurs
      in groups of cells, but high levels of protein accumulate in the nuclei of only a
      subset of the RNA-expressing cells. The pattern is dynamic and results in a small
      number of protein-containing cells that correspond to sensillum precursors.
      extramacrochaete loss-of-function alleles develop extra sensilla and
      correspondingly display a larger number of cells with scute protein. These cells
      appear to arise from those that in the wild type already express scute RNA;
      hence, extramacrochaete is a repressor of scute function whose action may take
      place post-transcriptionally.

PMID- 7821226
TI  - Regulation of a decapentaplegic midgut enhancer by homeotic proteins.
AB  - The clustered homeotic genes encode transcription factors that regulate pattern
      formation in all animals, conferring cell fates by coordinating the activities of
      downstream 'target' genes. In the Drosophila midgut, the Ultrabithorax (Ubx)
      protein activates and the abdominalA (abd-A) protein represses transcription of
      the decapentaplegic (dpp) gene, which encodes a secreted signalling protein of
      the TGF beta class. We have identified an 813 bp dpp enhancer which is capable of
      driving expression of a lacZ gene in a correct pattern in the embryonic midgut.
      The enhancer is activated ectopically in the visceral mesoderm by ubiquitous
      expression of Ubx or Antennapedia but not by Sex combs reduced protein. Ectopic
      expression of abd-A represses the enhancer. Deletion analysis reveals regions
      required for repression and activation. A 419 bp subfragment of the 813 bp
      fragment also drives reporter gene expression in an appropriate pattern, albeit
      more weakly. Evolutionary sequence conservation suggests other factors work with
      homeotic proteins to regulate dpp. A candidate cofactor, the extradenticle
      protein, binds to the dpp enhancer in close proximity to homeotic protein binding
      sites. Mutation of either this site or another conserved motif compromises
      enhancer function. A 45 bp fragment of DNA from within the enhancer correctly
      responds to both UBX and ABD-A in a largely tissue-specific manner, thus
      representing the smallest in vivo homeotic response element (HOMRE) identified to
      date.

PMID- 7821227
TI  - Expression of activin subunits, activin receptors and follistatin in
      postimplantation mouse embryos suggests specific developmental functions for
      different activins.
AB  - Using in situ hybridization we have studied the localization of the messenger
      RNAs encoding the inhibin/activin subunits (alpha, beta A, beta B), the activin
      binding protein follistatin and activin receptors (IIA, IIB) in mouse embryos
      during postimplantation development. From 6.5- to 9.5-days post coitum (p.c.)
      activin beta A and beta B subunit expression was restricted to the decidua, while
      activin receptor type IIB messages were exclusively detected in the embryo.
      Expression of activin receptor type IIA was apparent in the embryo as early as
      9.5 days p.c. In contrast, follistatin transcripts were present in both the
      decidua and the embryo at the early postimplantation stages. In particular, the
      primitive streak region, specific rhombomeres in the developing hindbrain,
      somites, paraxial mesoderm and parietal endoderm cells attached to the Reichert's
      membrane showed strong expression of follistatin. In 10.5- and 12.5-day embryos
      expression of the beta A subunit message was abundant in mesenchymal tissue, in
      particular in the developing face, the body wall, the heart, precartilage
      condensations in the limb and in the mesenchyme of structures that show both
      epithelial and mesenchymal components, including tissues of the embryonic
      digestive, respiratory and genital tracts. The distribution of beta B transcripts
      was quite different from that observed for beta A. beta B is strongly expressed
      in selected regions of the brain, in particular the fore- and hindbrain, and in
      the spinal cord. Specific hybridization signals were also present in the
      epithelium of the stomach and oesophagus. Common sites of beta A and beta B
      expression are blood vessels, intervertebral disc anlagen, mesenchymal
      condensations in the flank region and the gonad primordium. The latter organ is
      the only site in the embryo where the alpha subunit is expressed, and thus where
      inhibit activity may be present. During the period of organogenesis the sites of
      expression of activin receptors type IIA and IIB messenger RNA (mRNA) generally
      coincide with or are adjacent to the sites of beta subunit expression.
      Differences in the expression patterns of the receptor RNAs are the whisker
      follicles, where type IIA is expressed, and the metanephros and the forebrain
      where type IIB transcripts are present. Taken together, the present data suggest
      that follistatin, but not one of the known activin forms (A,B,AB) is involved in
      early postimplantation development.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7821228
TI  - XASH genes promote neurogenesis in Xenopus embryos.
AB  - Neural development in Drosophila is promoted by a family of basic helix-loop
      helix (bHLH) transcription factors encoded within the Achaete Scute-Complex (AS
      C). XASH-3, a Xenopus homolog of the Drosophila AS-C genes, is expressed during
      neural induction within a portion of the dorsal ectoderm that gives rise to the
      neural plate and tube. Here, we show that XASH-3, when expressed with the
      promiscuous binding partner XE12, specifically activates the expression of neural
      genes in naive ectoderm, suggesting that XASH-3 promotes neural development.
      Moreover, XASH-3/XE12 RNA injections into embryos lead to hypertrophy of the
      neural tube. Interestingly, XASH-3 misexpression does not lead to the formation
      of ectopic neural tissue in ventral regions, suggesting that the domain of XASH
      proneural function is restricted in the embryo. In contrast to the neural inducer
      noggin, which permanently activates the NCAM gene, the activation of neural genes
      by XASH-3/XE12 is not stable in naive ectoderm, yet XASH-3/XE12 powerfully and
      stably activates NCAM, Neurofilament and type III beta-tubulin gene expression in
      noggin-treated ectoderm. These results show that the XASH-3 promotes neural
      development, and suggest that its activity depends on additional factors which
      are induced in ectoderm by factors such as noggin.

PMID- 7821229
TI  - Beta-catenin localization during Xenopus embryogenesis: accumulation at tissue
      and somite boundaries.
AB  - beta-catenin is a cytoplasmic protein associated with cadherin adhesion molecules
      and has been implicated in axis formation in Xenopus (McCrea, P. D., Brieher, W.
      M. and Gumbiner, B. M. (1993) J. Cell Biol. 127, 477-484). We have studied its
      distribution in Xenopus embryos by immunofluorescence on frozen sections.
      Consistent with its function in cell-cell adhesion, beta-catenin is present in
      every cell. However, high levels are expressed in certain regions and different
      tissues of the embryo. No simple correlation appears to exist between the levels
      of beta-catenin with the expected strength of adhesion. High levels of beta
      catenin were found in regions undergoing active morphogenetic movements, such as
      the marginal zone of blastulae and gastrulae. This suggests that high expression
      of beta-catenin could be involved in dynamic adhesion events. Surprisingly, beta
      catenin also accumulates on plasma membranes that probably do not establish
      direct or strong contacts with other cells. In particular, high amounts of beta
      catenin are found transiently at boundaries between tissue anlagen and at the
      intersomitic boundaries. This unexpected pattern of beta-catenin expression
      raises the possibility that this molecule participates in developmental
      processes, perhaps independently of its classical role in cell-cell adhesion.

PMID- 7821230
TI  - Identification of a candidate primary sex determination locus, fox-1, on the X
      chromosome of Caenorhabditis elegans.
AB  - Sex in Caenorhabditis elegans (XX hermaphrodite, XO male) is determined by the
      X:A ratio, which is the ratio of X chromosome number to autosomal set number.
      Recent genetic results with X chromosome duplications have suggested that there
      may be only a small number of major numerator sites on the X chromosome that
      contribute to this ratio. Mapping of duplication endpoints delimited a region of
      less than 300 kb, likely to contain one such element. Cosmid clones from this
      region were tested for numerator activity by constructing transgenic lines
      carrying extra copies of each tested cosmid. Most cosmid arrays have no effect on
      the viability of either XX or XO animals. One cosmid array was found to be viable
      in XX animals, but lethal and feminizing in XO animals, consistent with it
      containing a major numerator element. Further experiments defined a region of 12
      30 kb with apparent numerator activity, which is designated fox-1, 'Feminizing
      locus On X'. A cDNA clone hybridizing across part of this region encodes a
      predicted RNA-binding protein.

PMID- 7821231
TI  - Lymphoproliferative response to mitogen (ConA) after treatment of rats with
      gentamicin and doxycyclin: relevance to human therapeutics.
AB  - Interaction of xenobiotics with the immune system may result in undesirable
      effects such as immunosuppression. In the future, it is probable that
      immunological screening tests may be required for safety evaluation of new drug
      candidates as an adjunct to more traditional toxicity testing. The
      lymphoproliferative response to mitogens has been proposed as a screening test.
      This test has been set up and validated in mice, but will probably have to be
      done in rats, the species of choice for drug safety studies. This test has been
      adapted to rats, using both in vivo and in vitro treatments, and used to validate
      drugs, including doxycyclin and gentamicin (with cyclosporin A and
      hydroxycortisone as controls) at the dose levels used in toxicology studies.
      Discrepant results obtained with doxycyclin and hydroxycortisone (effect in vitro
      but not in vivo) suggest that further validation studies are necessary in order
      to assess the reliability of this test.

PMID- 7821232
TI  - Effects of cyclosporin on kidney glutathione metabolism and cytochrome P-450 in
      the rabbit: possible implication of eicosanoid metabolism.
AB  - This study was designed to assess Cyclosporin A (CsA) nephrotoxicity in the
      rabbit-possibly a more sensitive species than the rat-and to explore the
      mechanism of this toxicity with special attention to glutathione metabolism
      disturbances and cytochrome P-450 level in the kidney. CsA given for three days
      at a daily dose of 50 mg/kg (s.c.) induced nephrotoxicity as assessed by
      histological abnormalities and by a significant increase in blood urea nitrogen
      and urinary enzyme activities: N-acetyl-beta-D-glucosaminidase and L-gamma
      glutamyl-transferase. This observed renal injury was of the same order as that
      obtained in the rat. In addition, there was a significant increase in oxidized
      glutathione content (40%) while reduced glutathione level remained unchanged.
      Concurrently, there was a significant decrease in renal cortex glutathione
      reductase (49%) and to a lesser extent in glutathione peroxidase activities (16%)
      whereas that of glutathione-S-transferase was not modified. A significant
      increase in renal cortex cytochrome P-450 (3-fold versus controls) was also
      observed. The mechanism of CsA nephrotoxicity is to be related to a cytochrome P
      450 induction. This event could induce the observed impairments in renal
      glutathione metabolism and Na+K(+)-ATPase activity, via a possible increase in
      eicosanoid metabolism.

PMID- 7821233
TI  - Ten and ninety-day toxicity studies of 1,2-dichloroethane in Sprague-Dawley rats.
AB  - Male and female Sprague-Dawley rats received 1,2-dichloroethane in corn oil by
      gavage for 10 or 90 consecutive days. The doses for the 10-day study were 10, 30,
      100, and 300 mg/kg; the 90-day study doses were 37.5, 75, and 150 mg/kg. There
      were ten animals per sex per dose group. In the 10-day study, all female animals
      died in the high dose group and only 2 of 10 males survived. Final body weights
      and weight gain along with hematology and clinical chemistry findings were not
      different from controls. The only relative organ weight which was significantly
      different was the liver in males exposed to 100 mg/kg. The main histopathological
      lesion exhibited was multifocal to diffuse inflammation of the mucosal and
      submucosal layers of the forestomach in the 100 mg/kg dose group. This change was
      minimal in both males and females. In the 90-day study there were no treatment
      related effects pertaining to clinical observations. Body weight gain and total
      food consumption were significantly decreased in high dose males. There were
      slight but significant differences in hemoglobin, hematocrit, red blood cell
      count, platelets, albumin, and alkaline phosphatase values in the 75 and/or 150
      mg/kg groups in one or both sexes. In males, relative brain, kidney, and liver
      weights were significantly increased at 75 and 150 mg/kg. There were also
      differences in spleen, adrenal, and testes weights (absolute and/or relative). In
      females, absolute and/or relative kidney and liver weights were significantly
      increased at 150 mg/kg (liver) and at 75 and 150 mg/kg (kidney). There were no
      apparent treatment-related effects pertaining to mortality, ophthalmology, gross
      pathology, or histopathology.

PMID- 7821234
TI  - The pharmacokinetics of inhaled 1,1,1-trichloroethane following high milk intake
      in mice.
AB  - In the evaluation of lipophilic halocarbons for neurobehavioral toxicity in
      operant testing, animals often receive large amounts of milk as a behavioral
      reinforcer over time. If this increase of fat in the diet sufficiently impacted
      the lipid depots of the animal, the pharmacokinetics of lipophilic test compounds
      might be significantly affected and thus obscure the accompanying neurobehavioral
      effects. The effects of milk intake, comparable to what was consumed as
      behavioral reinforcer during operant behavioral sessions, on the pharmacokinetics
      of inhaled 1,1,1-trichloroethane (TRI) were therefore examined in the blood and
      nine organ tissues of mice. Male CD-1 mice were food restricted so that their
      body weights would be reduced to and maintained at 80% of their original, and
      received a single gavage dose of 1.0 ml evaporated milk daily for three weeks. A
      control group with similar food restrictions was dosed with the same volume of
      water. Inhalation exposures to 3500 ppm TRI for 100 minutes were conducted at the
      end of the treatment period. Blood and nine organ tissues were sampled at a
      series of time points, and their TRI contents were analyzed by headspace gas
      chromatography. The uptake of TRI was rapid, with near steady state approached in
      blood and most tissues after 40-60 minutes of exposure. All of the tissues except
      fat had similar TRI time-concentration profiles, while TRI concentrations in fat
      tissue were about 20-30 times higher than in other tissues. There was no
      statistically significant difference in the tissue concentrations between the
      milk-dosed group and water-dosed group at all of the time points for all tissues
      measured. Therefore, it appears unlikely that this level of milk intake as a
      reinforcer in behavioral studies will affect the results of operant testing
      evaluations by altering the pharmacokinetics of lipophilic halocarbons such as
      TRI.

PMID- 7821235
TI  - Hypochlorite solution as a decontaminant in sulfur mustard contaminated skin
      defects in the euthymic hairless guinea pig.
AB  - Hypochlorite solutions are thought to be efficacious when used to topically
      decontaminate intact skin. However, few studies have examined the efficacy of
      decontamination of chemically contaminated wounds. Therefore, we compared the
      decontamination efficacy of sodium hypochlorite (0.5% and 2.5% solutions),
      calcium hypochlorite (0.5% and 2.5% solutions) and sterile water to untreated
      controls in wounds exposed to sulfur mustard (HD). Anesthetized euthymic hairless
      guinea pigs (EHGP) (n = 6) were exposed to 20 mg/kg (approximately 0.4 LD50) HD
      in a full-thickness 8 mm surgical biopsy skin defect (i.e., wound). Each animal
      was subsequently decontaminated, after a two-minute intra-wound exposure to
      liquid HD, with nothing or one of the decontamination solutions. Decontamination
      efficacy was determined by the visual grading of the HD-traumatized wound lesion
      and by comparison of the expected HD-induced leukocyte suppression. Leukocyte
      suppression was inconsistent in all animals; therefore, the visual grading was
      the only viable evaluation method. No significant differences were observed among
      wounds decontaminated with any of the solutions. However, the skin surrounding
      non-decontaminated (but exposed) control animals showed the least visual
      pathology. The lesions induced following decontamination are presumed to be due
      to the mechanical flushing of HD onto the peri-lesional skin, or by chemical
      damage induced by the solution, or HD-solution interaction. Further studies are
      required to best delineate the optimal decontamination process for HD
      contaminated wounds.

PMID- 7821236
TI  - Plasmids and antimicrobial drug resistance in bacteria.

PMID- 7821237
TI  - Plasmid profiles of E. coli, Salmonella and shigella organisms isolated in Kenya.
AB  - A number of serotypable E. coli, Salmonella and Shigella strains isolated from
      three districts in Kenya were investigated for carriage of plasmids. This was
      done through extraction of plasmids and separating them by electrophoresis on
      agarose. Most of the strains investigated showed presence of plasmids. The E.
      coli isolates had plasmids ranging in number from 1 to 5, the most common number
      was 2. The plasmid sizes ranged from 80 to 30 megadalton, the commonest of the
      heavy plasmids were 70 megadalton. The Shigella isolates had plasmids ranging in
      number from 1 to 3, the most common number was 1. The plasmid sizes ranged from
      80 to 3.5 megadalton, the commonest of the heavy plasmids were 70 megadalton.
      Various plasmid-sizes have been published as being responsible for pathogenicity.

PMID- 7821238
TI  - Resistance of E. coli strains, recovered from chickens to antibiotics with
      particular reference to trimethoprim-sulfamethoxazole (septrin).
AB  - Thirty-seven strains of E. coli recovered from cases of septicaemia in chicken
      were tested for sensitivity to 6 antibiotics. Minimum inhibitory concentration
      (MIC) determinations done on the strains showed resistance to trimethoprim
      sulfamethoxazole (septrin) (100%), ampicillin (62.2%), tetracycline (51.4%),
      kanamycin (13.5%) and gentamicin (2.7%). All were sensitive to chloramphenicol.
      Conjugation studies showed easy transfer of the resistance factor for septrin to
      the recipient sensitive strain, K12F-, a 60 megadalton plasmid was transferred in
      most of the cases (a number of plasmids moved across to K12F- strains). Septrin
      was chosen as a referral antibiotic because it is used extensively for treating
      diarrhoeal cases in children in Kenya. The results expressed the possibility of
      the chicken being the possible source of the septrin resistance gene (plasmid)
      for humans, and vice versa.

PMID- 7821239
TI  - Antibiotic residues in milk received by dairy cooperative societies in Kiambu
      district, Kenya.
AB  - A survey of antibiotic inhibitors in milk received by dairy cooperative societies
      in Kiambu district was done qualitatively using microbiological assay method. No
      antibacterial inhibitors were detected in all the samples tested. Informal
      discussions indicated a high level of awareness of the withdrawal requirement of
      veterinary drugs after animal treatment in both farmers and the management staff
      of dairy cooperative societies. The results show that milk from this area is free
      of antibiotic residues and farmers could be adhering to the withdrawal
      requirement of veterinary drugs. Such milk therefore does not pose a risk to the
      public and dairy industry.

PMID- 7821240
TI  - HIV seropositivity in children admitted with diarrhoea at Eldoret District
      Hospital, Kenya.
AB  - Fifty seven children aged 2 years and below admitted to Paediatric ward of
      Eldoret District Hospital with a diagnosis of diarrhoea were studied for HIV
      infection. A total of 29 (50.9%) cases were found to be positive with no gender
      difference. 17 (70.8%) of 24 cases with diarrhoea of over 14 days duration were
      positive for HIV compared to 12 (36.7%) cases out of 33 cases with diarrhoea of
      less than 14 days' duration. There was a high (80%) prevalence of HIV positivity
      rate in patients who presented with pneumonia and malnutrition in addition to
      diarrhoea when compared to children who presented with diarrhoea and vomiting
      alone (44.1%).

PMID- 7821241
TI  - Coliform counts and Escherichia coli in raw commercial milk from dairy farmers in
      Kiambu District, Kenya.
AB  - The rate of contamination with coliforms and incidence of Escherichia coli (E.
      coli) in raw milk supplied by farmers to dairy cooperative societies for
      marketing was investigated. About forty two (42.2%) percent of the milk samples
      from farmers cans and 10.3% of samples from cooperative cans were found to be
      free of coliforms, while 89.5% of the samples from farmers cans and 50% samples
      from cooperative cans could be considered to be of good quality with no more than
      50,000 coliforms/ml of milk. Forty two E. coli strains were isolated from milk
      samples, five of which were found to be enteropathogenic, while none was found to
      be of serogroup O157. The results indicated that a good number of farmers draw
      milk under satisfactory conditions, but awareness campaigns on clean milking,
      milk handling and storage practices should be stepped up in order to reach
      farmers who may not be informed. Again the study showed that raw milk can get
      contaminated with enteropathogenic strains of E. coli that can pose a potential
      risk to humans, thus calling for extra care when preparing milk and milk products
      that are to be consumed by human beings.

PMID- 7821243
TI  - Pattern of diverticular disease among Africans.
AB  - Diverticular disease of the colon was found to be a rare but emerging clinical
      problem among Urban Africans where 26 patients were recorded in this 5 year
      retrospective study, giving a hospital prevalence of 5 per 100,000 admissions.
      The pattern was different from that reported in Western communities in that,
      while diverticula were left sided in 77% of cases, 62% were right sided and 73%
      presented with haemorrhage. This confirms a reported experience among African
      Americans. We would like to postulate that it might be the pattern during a
      transition from traditional to Western diet.

PMID- 7821242
TI  - Colo-rectal carcinoma in a tropical African population: an overview report.
AB  - Fifty-one selected cases of colo-ano-rectal carcinoma seen in a tropical African
      population over a period of two decades were reviewed. The patients were divided
      into three groups. Group A were those cases seen under the age of thirty years,
      Group B were the resectable rectal carcinoma because they were bulky and occupied
      the whole of the pelvis. This we referred to as cases with "frozen" pelvis. Our
      modality of treatment consists of surgical excision when possible, the use of
      Levamisole, the use of 5-Fluoro-Uracil either intravenously, intraperitonealy and
      intrarectally as the case requires and radiotherapy when available. For Group A,
      the average survival period is 10.6 months, for Group B, it is 17.3 months and
      for Group C, it is 14.5 months. Symptoms of tenesmus and ascites improved by
      intrarectal and intraperitoneal infusion of calculated dose of 5-Fluoro-Uracil.

PMID- 7821244
TI  - Plasma retinol-binding protein levels of children under five years of age in a
      displaced Sudanese community.
AB  - Blood samples (100-160 microliters) were obtained from 1360 children by a finger
      prick in heparinized collection tubes, and an LC-Partigen retinol-binding protein
      (RBP) kit was used for quantification of RBP in the plasma. Only three boys and
      two girls had plasma RBP that was equal to or more than 3.0 mg/dL, a recommended
      cut-off point for normal values. The mean +/- SD) plasma RBP levels were at 1.150
      +/- 0.613 mg/dL for boys (N = 689) and 1.233 +/- 0.572 mg/dL for girls (N = 671).
      The difference between boys and girls was statistically significant (p < 0.001).
      None of the children included in this study had eye signs of vitamin A
      deficiency. Two hundred eighty-two children (19.6%) received vitamin A
      supplements (200,000 IU) before the beginning of the study. The mean +/- SD for
      plasma RBP for children who received vitamin A supplement were 1.159 +/- .762
      mg/dL for boys and 1.151 +/- 0.470 mg/dL for girls. The observed discrepancy
      between the biochemical and clinical manifestations of vitamin A deficiency was
      discussed.

PMID- 7821245
TI  - Inhibition of bloodmeal digestion in glossina morsitans fed on rabbits immunized
      with tsetse midgut homogenate.
AB  - The efficacy of bloodmeal digestion in teneral Glossina morsitans centralis fed
      on rabbits immunized with tsetse fly midgut extracts was progressively monitored
      over a period of 96 hours. Flies fed on immunized rabbits showed reduced rate of
      bloodmeal digestion as compared to the controls. Although there was insignificant
      difference in the rate of bloodmeal digestion upto 24 hours post-feeding in later
      stages of digestion there was quite a significant difference. Polyacrylamide gel
      electrophoretic patterns of bloodmeal drawn from the posterior sections of the
      midgut demonstrated that, bloodmeal is completely degraded in the midgut after 96
      hours in the control flies, while substantial amount is still undigested in the
      experimental flies. However, not much difference in the rates of digestion was
      observed with bloodmeal drawn from the anterior section of the midgut. These
      results suggests that when flies are fed on rabbits immunized with tsetse fly
      midgut extract, there is an impairment on the efficiency of digestion. The anti
      midgut antibodies could be interfering with either the induction or proteolytic
      activity of the midgut enzymes.

PMID- 7821246
TI  - Maternal mortality and related factors in Ejisu District, Ghana.
AB  - A community-based survey on maternal mortality was carried out in the Ejisu
      health district of Ghana in January and February 1990 to identify all women who
      died in pregnancy, delivery or the puerperium from January 1985 to December 1989,
      determine their characteristics, the presumptive causes of death and related
      factors. Forty-four women who died in pregnancy, delivery or the puerperium were
      identified over the stated period. 59% were aged between 20 and 34 years. Eighty
      two percent were married and sixty-six percent had at least primary education.
      Based on an average crude birth rate of 40 per 1000 population for the district
      over the period, the lowest maternal mortality rate occurred in 1988, 120 per
      100,000 total births and the highest occurred a year later, 235 per 100,000 total
      births. The main presumptive causes of maternal mortality in the district were
      postpartum haemorrhage 45.5%, jaundice in pregnancy 22.7%, obstructed labour
      6.8%, eclampsia 6.8% and fever 4.6%. 59% of them died in a hospital, 2% died at a
      Government Maternity Home and 7% died during referral from health facilities in
      the district. Thirty-four percent of the women who died did not attend any
      antenatal clinic. The actual number of deaths may be underestimated due to the
      sampling method used and the difficulties encountered in linking survey data with
      hospital records. Based on the survey findings and other related PMM research,
      plans have been developed to reduce maternal mortality in the district as outline
      in the conclusion.

PMID- 7821247
TI  - High-risk pregnancies in urban and rural communities in central part of Ethiopia.
AB  - A survey was conducted in 13 urban kebeles and 13 rural villages to assess the
      magnitude of high risk pregnancies. A total of 567 pregnant women were included
      in the study. Of these, 28.6% were younger than 20 or older than 34 years. Early
      marriage below the age of 20 were reported by 85%. 21.7% and 22.2% were
      nulliparous and multiparous women, respectively. 39.2% were illiterate and 42.9%
      with a very low income. 14.6% gave a history of abortion, 13.1% of infant deaths,
      6.3% of postpartum haemorrhage and 1.1% of antepartum haemorrhage. Abnormal
      height was recorded in 18.5%, Albuminuria in 11.5% and abnormal diastolic blood
      pressure in 12.2%, where 2.9% and 9.2% were classified as pre-eclamptic and
      gestational hypertensive. 52.3% were not receiving antenatal care services. Those
      who had at least one of the risk factors were 85%. The results from this study
      indicate the need for increased Family Planning services and appropriate
      training, and use of community health workers.

PMID- 7821248
TI  - Low birth weight deliveries at the Nyanza General Hospital Kisumu, Kenya.
AB  - The results of a four month descriptive study on low Birth weight (LBW)
      deliveries in Nyanza Provincial General Hospital, Kisumu from 15th March to 30th
      July 1987 are presented. The incidence of LBW was 15.0%. Premature labour
      accounted for 55.3% while term small for gestational age contributes 44.7% of all
      LBW babies. 4.8% of the mothers of LBW babies were teenagers. The mean gravidity
      of the mother's was 2.5 with 46.8% being primigravidae. Of the multiparae who
      delivered LBW babies: 26.6%, 25%, 12.9% and 12.1% gave history of previous
      abortion, premature delivery, neonatal death and stillbirth respectively. The
      most common antenatal complications associated with LBW delivery were pyrexia
      (20.2%), premature rupture of membranes before term (16.7%) and multiple
      pregnancy (14.6%). 82.4% of LBW deliveries were spontaneous vertex delivery,
      12.5% vaginal breech delivery and 2.9% caesarean section. The worst perinatal
      outcome was associated with caesarean section while spontaneous vertex delivery
      had the best outcome. Other factors associated with good perinatal outcome were
      increasing birth weight; first stage of labour lasting less than 18 hours and
      small for gestational age babies.

PMID- 7821249
TI  - Anaemia in pregnancy.
AB  - Four hundred and thirty-five pregnant women attending the antenatal clinic at the
      University of Benin Teaching Hospital (UBTH) were investigated. The ages of the
      women ranged from 16-42 years with an average haemoglobin level of 10.52 gms%.
      The prevalence rate of anaemia among these antenatals was 20.7% and 2.8% had
      severe anaemia. This shows that anaemia is still a problem in Nigeria. Mothers in
      the age groups 10-19 years and 30-39 years constituted higher percentages of
      anaemic cases compared to the other age groups. The percentages of the pregnant
      women who were anaemic were also higher in social-classes IV and V contributing
      27.6% and 21.9% respectively. One hundred and eight (49.4%) of the pregnant women
      booked for antenatal care during the 3rd trimester and the percentage of anaemia
      was highest in this group 54 (28.4%). About half of the mothers who were para 5+
      were anaemic. Nutrition education components of the antenatal care should be
      intensified. In this regard, mothers should be encouraged to participate actively
      in income generating activities to improve their economic and nutritional status.
      Also, during the health education activities in the clinics, the importance of
      family planning and early bookings for antenatal care need to be stressed.

PMID- 7821250
TI  - Intralesional triamcinolone acetonide in alopecia areata amongst 62 Saudi Arabs.
AB  - Evaluation of 62 Saudi Arabs with alopecia areata on monthly intralesional
      injection of triamcinolone acetonide, showed complete regrowth in 40 (63%)
      patients at 4 months. Regrowth was likely in young adults with few lesions (less
      than 5 patches), lesions of short durations (less than 1 month) patches less than
      3 cm in diameter. Regrowth was poor when associated with atopy (2 patients) and
      mongolism (1 patient). Side effects of treatment were minimal and the drug was
      well tolerated.

PMID- 7821251
TI  - An experience with trial of scar in 66 Ethiopian women.
AB  - The purpose of this study was to determine the circumstances in which trial of
      scar is conducted in the obstetric unit of Tikur Anbessa Hospital, Addis Ababa,
      Ethiopia, and evaluate the safety of the undertaking in terms of maternal and
      perinatal morbidity and mortality. Between 11 September, 1991 to 10 September,
      1992, 66 women with previous caesarean section were given a trial of scar. The
      main pre-requests to allow a trial of scar were: only one previous lower uterine
      segment section, a cephalic presentation with no disproportion in the current
      labour and, the presence of a functional operating theatre. Labour was being
      monitored by checking the uterine contractions by fundal palpation and counting
      the Foetal heart rate (FHR) using the Pinnard Stethoscope. Compatible blood was
      prior prepared in only 7 (10.6%) labours. Forty seven (71.2%) parturients
      delivered vaginally. In 19 (28.2%) an emergency repeat section was done for
      failure of progress in labour. In one (1.5%) patient, a uterine scar dehiscence
      was detected. The 5th minute APGAR score was 7/10 or more in 64 (94.1%) and 6/10
      in 3 (4.5%) of 68 neonates. There was one prepartum intra-uterine foetal death
      and one neonatal death of a preterm baby making the perinatal mortality rate
      (PNMR) of 29.4 per thousand. There was no maternal death. In conclusion, this
      study demonstrates that a trial of scar was a safe procedure.

PMID- 7821252
TI  - The use of reagent strips for detection of urinary schistosomiasis infection in
      the middle Awash Valley, Ethiopia.
AB  - Reagent strip test was carried out to detect haematuria in urinary
      schistosomiasis infection in ten schools (1114 children) in the middle Awash
      Valley, Ethiopia. In five schools (557 children), were compared with results of
      urine filtration technique conducted simultaneously. The prevalence of infection
      by reagent sticks and urine filtration was 19.5% and 3.1%, respectively.
      Haematuria, detected by the reagent strip, was highly related with the results of
      urine filtration at the 2+ limit rather than the 1+ limit. However, the intensity
      of infection of all children was highly associated with prevalence rate at both
      haematuria limits. The possible use of reagent strips in Ethiopia to monitor
      morbidity (haematuria) due to S. haematobium infection is discussed.

PMID- 7821253
TI  - Thoracic empyema in Dar es Salaam, Tanzania.
AB  - A review of 114 thoracic empyema cases attended in the thoracic unit of the
      Muhimbili Medical Centre from July 1986 to July 1990 is presented. 87.7% of the
      cases were males. Their ages ranged from 9 to 79 years with a mean of 32 years.
      Tuberculosis was the major cause accounting for 63.2% of all the cases. 53.4% of
      the patients underwent either open chest drainage decortication or thoracoplasty.
      The duration of hospital stay ranged from 2-8 months with a mode around 3.5
      months. A 7% mortality was noted.

PMID- 7821254
TI  - Alternative technique of constructing bilateral cleft palate in late childhood: a
      case report and literature review.
AB  - Although great advances in treatment of oro-facial clefts have been made over the
      past 50 years; in developing countries, due to social stigmas and unavailability
      of specialised medical facilities and personnel to the majority of the
      population, there is an increasing incidence of patients coming late for repair
      of oro-facial clefts. This presents a challenge to both plastic, oral surgeons
      and associated specialists. The aim of the present article is to demonstrate, in
      the form of a case report, an alternative surgical technique that has be
      successful in 8 cases for the late repair of severe bilateral cleft palate
      utilizing locally available and affordable materials. The objective of managing
      patients with cleft palate in developing countries is to provide the best repair
      and rehabilitation with as few operations and in-patient care as possible due to
      limited financial resources experienced by the majority of in-patients. A
      multidisciplinary approach to the management of oro-facial clefts is emphasised.

PMID- 7821255
TI  - Ethnicity and the sudden infant death syndrome. Papers from a conference.
      Cardiff, United Kingdom, June 25, 1993.

PMID- 7821256
TI  - Ethnicity and the sudden infant death syndrome: an introduction.

PMID- 7821257
TI  - Ethnic differences in the sudden infant death syndrome: what we can learn from
      immigrants to the UK.
AB  - AIMS: To compare the effect of potential maternal and birth factors on rates of
      sudden infant death syndrome (SIDS) within and between infants born to mothers of
      different ethnic groups. METHODS: Routinely collected obstetric, child health
      data relating to 39,101 residents of three East London Districts born in 1989
      1990 were obtained. These were matched with 312 death registration records to
      validate death and add registered cause of death. Mortality rates were calculated
      in the usual way, and using life-table methods. RESULTS: These related to six
      ethnic groups, the largest of which were Anglo-European and Bangladeshi. Low
      birth-weight was the only factor associated with a greater risk of SIDS in all
      ethnic groups. Maternal smoking was uncommon amongst all Asian groups and African
      mothers, and rates of SIDS were uniformly low amongst non-smokers in all ethnic
      groups except Pakistanis. Adjustment for maternal age, parity, gestational age
      and birthweight would widen the differences between risk of SIDS observed between
      Anglo-Europeans and Bangladeshi infants. CONCLUSIONS: The study has demonstrated
      that local data is more timely and of greater detail than that available
      nationally. Of the risk factors considered, smoking reported during pregnancy is
      the most commonly encountered and is particularly associated with deaths
      attributed to SIDS.

PMID- 7821258
TI  - Observations on ethnic differences in SIDS mortality in New Zealand.
AB  - INTRODUCTION: Within New Zealand the SIDS mortality rate is higher in Maori than
      in non-Maori, predominantly European. AIMS: This paper addresses two questions
      (1) How should ethnicity be defined, by biological or cultural criteria? (2) Why
      is the SIDS rate higher in Maori, because of different risk factors or because of
      a higher prevalence of common risk factors? METHODS: A nationwide case-control
      study. RESULTS: The majority of mothers with some Maori blood (as reported on the
      infants birth registration form) report they are Maori (as recorded in the
      obstetric records or interview). Risk factors for SIDS are similar in the various
      ethnic groups in New Zealand. CONCLUSIONS: Using a biological definition
      underestimates the number of Maori infants compared to the cultural definition.
      Differences in SIDS mortality appear to be explained by differences in prevalence
      of known risk factors, the most important of which, prone sleeping position,
      maternal smoking, lack of breast feeding and bed sharing, are culturally
      determined rather than biologically.

PMID- 7821259
TI  - Infant mortality in ethnic minorities in Yorkshire, UK.
AB  - Post-perinatal infant mortality in Yorkshire 1991-1993 was higher among non
      whites (mainly Pakistanis) than among whites (5.7/1000 vs. 4.9/1000 live births).
      Pakistani families had more deaths from congenital or metabolic abnormalities,
      and from perinatal factors, but far fewer than sudden infant death syndrome.

PMID- 7821260
TI  - SIDS: risk reduction measures.
AB  - Increasing public awareness of the prone sleeping position, maternal smoking and
      overheating as potentially avoidable risk factors for the sudden infant death
      syndrome (SIDS) has been accompanied by a dramatic reduction in mortality. The
      results of two population based studies of SIDS in Avon are compared; the first
      one occurred before these risk factors were widely known and during the second
      study there was a gradual increase in publicity. Between the studies the
      prevalence of prone sleeping in the control populations fell significantly from
      60% to 28% and almost all of the reduction in SIDS mortality (3.5 to 1.7 per
      thousand live births) could be attributed to this change. Other changes were also
      found: the seasonal pattern of incidence was lost, the proportion of expreterm
      babies increased and the male predominance was accentuated. The relative
      importance of smoking and bottle feeding appeared to increase whereas the odds
      ratios for heavy wrapping and overnight heating were no longer significantly
      elevated. Small numbers limit the significance of these individual variations but
      demonstrate that changes are occurring. Local and national public health
      campaigns have been launched in the UK and abroad to encourage infant care
      practices that reduce the risk of SIDS. Monitoring the effectiveness of these
      campaigns is important and may allow new risk factors to be identified which
      could in turn be targeted in future preventative campaigns. Significant
      reductions in mortality have followed these initial campaigns but in order to
      maintain them the message must be regularly renewed using an appropriate approach
      and effective channels of communication to target high risk families within the
      community.

PMID- 7821261
TI  - Infant care practices and the investigation of physiological mechanisms.
AB  - It is strange that some aspects of infant care have been strongly promoted by
      modern medicine while others have been neglected. Thus prone sleeping which has
      been strongly promoted is now related to an increase in SIDS, whereas the
      promotion of breast feeding in developed countries has been less successful.
      Unfortunately there has not been sufficient physiological investigation of many
      infant care practices and some of the proposed mechanisms for SIDS and prone
      sleeping have not been substantiated. Thus further work is needed on hypercapnia,
      hypothermia and periodic breathing and respiratory control. Studying infants
      alone may leave out important physiological mechanisms such as the effect on body
      warmth when the infant is close to the mother. More investigation is needed of
      antenatal factors related to SIDS and it is critically important that
      physiological investigation should not look for single mechanisms but be
      concerned with the interaction of many physiological factors.

PMID- 7821262
TI  - Interactions between infant care practices and physiological development in Asian
      infants.
AB  - Asian infants are less likely to suffer cot death despite apparently higher
      prevalence of some risk factors. This paper compares the development of night
      time body temperature patterns in a small sample of Asian babies with the pattern
      already established for white infants, where babies who develop an adult-like
      night time temperature pattern later than usual share characteristics with
      victims of SIDS. The Asian infants had similar body temperature patterns to
      whites, but tended to develop the adult-like pattern later, not earlier as might
      have been expected. More Asian infants than white in our sample slept in the
      parental bed, and, before the adult-like body temperature patterns appeared, co
      sleeping infants had higher body temperatures than those in their own cots. Asian
      infants slept in significantly warmer rooms than whites, but under similar
      amounts of bedding. These studies do not therefore reveal any physiological
      difference between Asians and whites which might account for low vulnerability to
      cot death, indeed, if anything the reverse.

PMID- 7821263
TI  - Experimental studies of infant-parent co-sleeping: mutual physiological and
      behavioral influences and their relevance to SIDS (sudden infant death syndrome).
AB  - We hypothesize that maternal sensory exchanges, likely involving a combination of
      heat, sound, gas, smells, movement, and touch, induce important physiological
      changes, especially in the healthy infant's arousal patterns, body temperature,
      and sleep architecture as defined by standard physiological measures. We
      summarize the results of two preliminary physiological studies, and some early
      data from a third, in which mothers and infants are monitored using standard
      polysomnographic techniques as they sleep in the same bed, and then in adjacent
      rooms. Our data suggest that infant-parent co-sleeping alters the infant's sleep
      experience as, for example, the characteristics of arousals, the frequency and
      duration of nursing, infant sleep position and the number of maternal
      inspections. For example, while sleeping in the same bed, mothers nurse their
      infants three times more frequently than they do while their infants sleep in an
      adjacent room. These preliminary data demonstrate significant differences between
      routine co-sleeping and solitary sleeping environments. This work underscores the
      importance of studying infant sleep as it unfolds in the co-sleeping environment,
      the environment within which it evolved over at least 5 million years of human
      evolution. Should our preliminary findings be confirmed in future studies they
      will provide a beginning point for considering additional, possibly
      unconventional ways of helping to reduce SIDS risks.

PMID- 7821264
TI  - Ethnicity and the sudden infant death syndrome: anthropological perspectives.
AB  - Comparative data on infant caring practices among Bangladeshi and Welsh families
      in Cardiff, and among Maori and white families in New Zealand, reveal qualitative
      differences in the infant sensory environment. An anthropological perspective is
      adopted to place SIDS, lone infant sleeping and parent:infant co-sleeping in a
      broader cultural context.

PMID- 7821265
TI  - Ethnic differences in infant care practices and in the incidence of sudden infant
      death syndrome in Birmingham.
AB  - Certain infant care practices have consistently been shown to play an important
      role in the aetiology of the sudden infant death syndrome (SIDS). In the UK, the
      incidence of SIDS amongst Asians is less than half that of whites. We conducted a
      questionnaire-based survey of 374 multiparous mothers from a multiracial
      community in Birmingham. We found that the majority of Asian infants slept in the
      parental bedroom at night, 94% compared to 61% of whites, whilst 33% of white
      infants slept alone compared to 4% of Asians. Three times as many white mothers
      as Asians placed infants prone (31% vs. 11%). We, therefore, observed marked
      differences in the infant care practices of Asians compared to whites in the UK,
      which may partly account for the low incidence of SIDS amongst infants of Asian
      origin.

PMID- 7821266
TI  - Ethnicity and SIDS: what have we learnt?

PMID- 7821267
TI  - Benzodiazepine-GABAA receptors in idiopathic generalized epilepsy measured with
      [11C]flumazenil and positron emission tomography.
AB  - The neurochemical basis of absence seizures and the mechanism of their
      suppression by valproate (VPA) are uncertain. We used positron emission
      tomography (PET) to determine whether an abnormality of [11C]flumazenil binding
      to benzodiazepine (BZD)-GABAA receptors exists in patients with childhood and
      juvenile absence epilepsy and to examine the effects of VPA on [11C]flumazenil
      binding. The regional cerebral volume of distribution (Vd) of [11C]flumazenil in
      patients not treated with VPA was not different from that in normal controls; Vd
      was lower in patients treated with VPA, and the number of receptors available for
      binding was significantly reduced in such patients as compared with normal
      controls. There was no evidence of a primary abnormality of the BZD-GABAA
      receptor in childhood and juvenile absence epilepsy (CAE/JAE), but the data
      suggest that treatment with VPA is associated with a reduction in [11C]flumazenil
      binding that may be relevant to its mode of action in CAE/JAE.

PMID- 7821268
TI  - Focal intermittent delta activity in patients with mesiotemporal atrophy: a
      reliable marker of the epileptogenic focus.
AB  - We attempted to determine the significance of background abnormalities and their
      relation with spikes and location of atrophy in 56 patients with temporal lobe
      epilepsy (TLE) and mesiotemporal atrophy (MTA) assessed by volumetric magnetic
      resonance imaging (MRI): 35 patients had unilateral (group I) and 21 had
      bilateral atrophy with lateralized predominance (group II). Trains of delta waves
      over temporal regions were observed in > or = 90% of patients. They lateralized
      with accuracy equal to that of the spikes to the site of atrophy (delta 92% or 29
      of 32 patients in group I and 63% or 12 of 19 of group II; spikes 85% or 28 of 33
      of group I and 65% or 13 of 20 of group II). Delta waves and spikes occurred
      together in > 85% of cases. With respect to their location, a striking
      concordance was observed: delta activity almost always occurred ipsilateral with
      unilateral spiking (90% or 19 of 21 of patients with unilateral and 88% or 7 of 8
      of patients with bilateral atrophy) and bilaterally independently with bilateral
      spiking (67% or 6 of 9 of patients in group I and 100% or 10 of 10 in group II).
      Furthermore, spiking and delta activity were never in disagreement with respect
      to lateralization. In TLE related to MTA, delta transients are a reliable
      indicator of the epileptogenic focus and presumably reflect the epileptogenic
      process rather than the underlying structural pathology.

PMID- 7821270
TI  - Relationship of age at onset, chronologic age, and adequacy of preoperative
      performance to verbal memory change after anterior temporal lobectomy.
AB  - We examined the relationship of age of onset of epilepsy, chronological age at
      time of operation, and adequacy of preoperative memory performance to pre- to
      postoperative verbal memory decline. Patients who underwent left (n = 50) or
      right (n = 51) anterior temporal lobectomy (ATL) were administered tests of
      verbal episodic (list learning, paragraph recall) and semantic memory (visual
      naming, vocabulary), both preoperatively and 6 months postoperatively. As a
      group, left ATL patients showed the classic selective decrease on measures of
      episodic but not semantic memory. However, examination of episodic memory outcome
      showed considerable individual variability. Stepwise regression analyses
      indicated that both later age at onset and older chronologic age were significant
      and selective predictors of episodic memory decrease for left ATL patients.
      Adequacy of preoperative memory performance was a nonspecific predictor,
      associated with decrease in postoperative memory performance for both left and
      right ATL patients and for multiple types of memory indices. The clinical and
      theoretical implications are discussed.

PMID- 7821269
TI  - Language function after temporal lobectomy without stimulation mapping of
      cortical function.
AB  - We studied 95 patients who underwent standard anterior temporal lobectomy (ATL)
      without stimulation mapping of language areas, using neuropsychological
      parameters of language function preoperatively and 1 year postoperatively [Boston
      Naming Test and Verbal Fluency, and the Information, Comprehension, Arithmetic,
      Similarities, Digit Span, and Vocabulary subtests of the Wechsler Adult
      Intelligence Scale (WAIS)]. Verbal IQ (VIQ), Performance IQ (PIQ), Full-Scale IQ
      (FSIQ), and Verbal Deviation Quotient were also evaluated, as were parameters of
      memory function. All patients had hemisphere dominance for language assessed by
      an intracarotid amytal test. Fifty-three patients had a left dominant (LHDL) ATL
      with a mean extent of lateral resection of 4.8 cm, and 10 had a left ATL with
      right or mixed hemisphere dominance (RHDL, MDL). Thirty-two patients had a right
      nondominant ATL. Seizure outcome was 57 and 59% seizure-free for LHDH and right
      nondominant group, respectively, 1 year after operation. Comparison of
      preoperative scores showed the LHDL group to have significantly lower scores than
      the right nondominant group for several parameters of language function and
      memory. The group undergoing left dominant ATL showed no significant loss of
      language function postoperatively and actually showed gains in many parameters.
      Standard ATL without stimulation mapping of language areas and with conservative
      lateral resection is safe for long-term language function. In addition, evidence
      shows preexisting language dysfunction in patients undergoing left dominant ATL.

PMID- 7821271
TI  - Metabolic abnormalities and new-onset seizures in human immunodeficiency virus
      seropositive patients.
AB  - Seizures are a recognized complication of human immunodeficiency virus (HIV)-type
      1 infection. CNS disease processes in these patients include encephalitis, focal
      brain lesions, and meningitis. Metabolic causes of seizures have received little
      attention. In a retrospective study, we selected 68 HIV-seropositive patients
      with new-onset seizures and information available for specified metabolic factors
      on the day of the first seizure. We sought an association of metabolic
      abnormalities with convulsive status epilepticus (CSE), which was the initial
      seizure in 12 patients, predominantly intravenous (i.v.) drug users. HIV
      seropositive patients with new-onset seizures and hypomagnesemia or renal failure
      appeared to be at increased risk for CSE. All HIV-seropositive patients with new
      onset seizures should undergo metabolic screening including renal function and
      serum magnesium levels.

PMID- 7821272
TI  - Epileptic spasms in older children: persistence beyond infancy.
AB  - Although infantile spasms (IS) constitute a well-recognized epileptic syndrome,
      only recently did investigators propose that spasms be classified as a distinct
      seizure type, characterized by axial flexion/extension jerks in clusters. Five
      older children (aged 4.5-14.2 years) who underwent video-EEG monitoring in 1992
      in our epilepsy program for intractable mixed seizure disorder (cryptogenic 1,
      symptomatic 4) demonstrated flexor and extensor spasms in clusters. Seizure onset
      was from birth to 1.33 years. All 5 had spasms during infancy that continued as
      the children aged. Ictal EEG during spasms showed a brief high-amplitude delta
      burst followed by diffuse background attenuation or diffuse background decrease
      with superimposed rhythmic beta or alpha activity. Multiple other seizure types
      were present. Interictal EEGs were markedly abnormal and demonstrated slowing,
      multifocal spikes, generalized slow spike-wave, and polyspike-wave. Two children
      with spasms were unsuccessfully treated with ACTH, and 3 underwent corpus
      callosotomy. We conclude that spasms occur in older children with intractable
      mixed seizure disorders and may persist beyond infancy.

PMID- 7821273
TI  - Cerebral blood flow during spike-wave discharges.
AB  - We used the 133xenon method to assess cerebral blood flow (CBF) during
      generalized spike-wave discharges in a patient with an uncommon form of
      generalized epilepsy with persistent spike-wave discharges. CBF measurements were
      made under four conditions with repeated measures: normal EEG, continuous theta
      state, continuous spike-wave state at rest, and continuous spike-wave discharges
      during performance of a cognitive activation task. CBF was mildly reduced (5.7%)
      during the theta state and decreased further (12%) in the spike-wave state.
      Although globally diminished, CBF was less decreased in the frontal lobes and
      more decreased in the parietal lobes during spike-wave discharges. CBF increased
      to baseline levels during the cognitive activation task. The decrease in CBF
      suggested that the generalized spike-wave discharges caused a net decrease in
      cortical metabolic demand and neuronal activity. The differences in lobar CBF
      during spike-wave discharges may reflect lobar disparities in neuronal firing
      patterns. The theta state noted is novel and intermediate between normal and
      spike-wave.

PMID- 7821274
TI  - Effects of differing dosages of vigabatrin (Sabril) on cognitive abilities and
      quality of life in epilepsy.
AB  - Vigabatrin (VGB) prevents seizures by irreversible inhibition of gamma
      aminobutyric acid (GABA) transaminase and a resulting increase in GABA levels. We
      evaluated the cognitive and quality-of-life (QOL) effects of VGB in a double
      blinded, add-on, placebo-controlled, parallel group dose-response study of
      patients with focal epilepsy whose complex partial seizures (CPS) were difficult
      to control. In a single investigation, patients were randomly assigned to placebo
      (n = 40), 1 g VGB (n = 36), 3 g VGB (n = 38), or 6 g VGB (n = 32), treated for 12
      weeks after a 6-week dose escalation period, and tested at the end of the
      baseline period and at the end of the treatment period with eight cognitive
      measures and three tests of mood and adjustment. The patient groups were highly
      similar at study entry. Results at the end of the study showed substantial relief
      from seizures. The Digit Cancellation Test showed decreases in performance with
      increasing doses of VGB. Performance on no other test showed any decrement with
      increasing dosage. Relief from seizures was not associated with changes on the
      psychological tests. VGB is a useful antiepileptic drug (AED) that has little
      impact on tests of either cognitive abilities or QOL, even at a high dose.

PMID- 7821276
TI  - Effects of MK-801 and phenytoin on flurothyl-induced seizures during development.
AB  - We determined the effects of the N-methyl-D-aspartate (NMDA) receptor blocker MK
      801 (0.05, 0.1, and 0.5 mg/kg intraperitoneally, i.p.) and phenytoin (PHT, 5, 10,
      and 20 mg/kg i.p.) on flurothyl-induced clonic and tonic-clonic seizures in 9-,
      15-, 30-, and 60-day-old male rats. Both agents had seizure-, age-, and dose
      specific effects. The highest dose of MK-801 was anticonvulsant against clonic
      flurothyl-induced seizures only in 9- and 60-day-old rats, but suppressed tonic
      clonic seizures in all ages. The lowest dose of MK-801 (0.05 mg/kg) produced
      significant anticonvulsant effects only in 15 day old rats. PHT did not have any
      effect on clonic seizures throughout development. Both doses of PHT (10 and 20
      mg/kg) were anticonvulsant against tonic-clonic seizures in adult rats but not in
      any other age group. The results indicate that NMDA receptors play an important
      role in tonic-clonic flurothyl-induced seizures throughout development
      (especially in 15-day-old rats) and that the anticonvulsant effects of PHT may
      vary at different stages of brain development.

PMID- 7821275
TI  - ACTH does not control neonatal seizures induced by administration of exogenous
      corticotropin-releasing hormone.
AB  - ACTH has been used extensively for treatment of massive infantile spasms (MIS)
      and other intractable seizures. The mechanisms by which ACTH exerts
      anticonvulsant effects are unknown. ACTH is a neuropeptide with both endocrine
      and neuromodulatory properties; its efficacy against MIS could derive from
      intrinsic anticonvulsant properties or from hormonal effects, either directly or
      through glucocorticoids. We tested ACTH activity against exogenous corticotropin
      releasing hormone (CRH)-induced seizures in the infant rat model. CRH was
      administered into the cerebral ventricles of 85 infant rats aged 5-13 days. ACTH
      was used either 20-60 min before CRH administration or "chronically"
      (pretreatment with four doses of ACTH every 6 h, before CRH administration). In a
      separate group of rat pups, we measured plasma corticosterone to ascertain ACTH
      availability. Administration of CRH, an age-specific endogenous convulsant,
      resulted in a prolonged series of seizures after 2- to 55-min latency. There was
      no difference in latency between controls (9.5 +/- 1.2 min) and ACTH-treated rats
      (12.4 +/- 2.8 min for combined acute and chronic groups). CRH-induced seizure
      duration (88.2 +/- 9 vs. 74.7 +/- 9.4 min) and severity of seizures was also
      unchanged by ACTH treatment. ACTH reached the circulation and caused significant
      increase in plasma glucocorticoids. ACTH does not block the convulsant action of
      exogenous CRH in infant rats. An alternative mechanism for the anticonvulsant
      effect of ACTH may be suppression of synthesis and secretion of an endogenous
      convulsant, i.e., CRH.

PMID- 7821277
TI  - Neuroprotective effect of ketamine administered after status epilepticus onset.
AB  - We investigated the neuroprotective effect of the noncompetitive N-methyl-D
      asparatate (NMDA) antagonist ketamine when administered after onset of lithium
      pilocarpine-induced status epilepticus (SE). Seizures were induced in Wistar rats
      with lithium chloride (3 mEq/kg) and pilocarpine (PC) (30-60 mg/kg
      intraperitoneally, i.p.). Fifteen minutes after SE onset, either ketamine 100
      mg/kg or normal saline was injected i.p., and 3 h after SE onset atropine,
      diazepam (DZP), and phenobarbital (PB) were administered i.p. to terminate the
      seizures. Twenty-four hours later, rats underwent brain perfusion-fixation, with
      subsequent brain processing for light-microscopic examination. Rats adminstered
      saline (n = 5) had neuronal damage in 24 of 25 brain regions examined. Rats
      administered ketamine (n = 7) had significant neuroprotection in 22 of 24 damaged
      regions. Ketamine reduced the amplitude of seizure discharges, and in 3 rats EEG
      seizure activity ceased in 30 min; none of these rats had neuronal damage. In the
      other 4 rats, EEG seizure discharges persisted > 90 min; in these animals, 21 of
      24 damaged regions were protected. In contrast, rats with 1-h high-dose PC
      induced SE (400 mg/kg i.p. without lithium chloride preadministration) had 14
      damaged regions, of which 7 were significantly different from the undamaged
      regions of the ketamine subgroup with persistent electrographic seizures. Thus,
      ketamine is remarkably neuroprotective when administered after onset of SE,
      whether or not seizure discharges are eliminated.

PMID- 7821278
TI  - Effects of glutamate, N-methyl-D-aspartate, high potassium, and hypoxia on unit
      discharges in CA1 area of hippocampal slices of DBA and C57 mice.
AB  - We studied effects of L-glutamate, N-methyl-D-aspartate (NMDA), high K+, and
      hypoxia on spontaneous unit discharges in stratum pyramidale of CA1 region of
      hippocampal slices in DBA and C57 mice aged 3-4 and 5-6 weeks. Application of L
      glutamate (0.5-2.0 mM), NMDA (5-20 microM), high K+ (8.5 mM), and a brief period
      of hypoxia (1 min) to the perfused artificial cerebrospinal fluid (ACSF) all
      produced different degrees of spontaneous high-frequency discharges from CA1 area
      of hippocampal slices of both DBA and C57 mice. Two types of responses recorded
      extracellularly occurred after these manipulations: high-frequency repetitive
      single spikes and bursts of multiple population spikes. The rate and type of
      responses from CA1 region of hippocampal slices after these manipulations were
      different and depended on the strain and age of mice and the nature of
      manipulations. In general, hippocampal slices from audiogenic seizure-susceptible
      DBA mice were more sensitive than those from audiogenic seizure-resistant C57
      mice, and hippocampal slices from younger animals were more susceptible than
      those from older ones. Thus, DBA mice aged 3-4 weeks of age were most susceptible
      and C57 mice aged 5-6 weeks were least susceptible to all these pharmacological,
      ionic, and hypoxic manipulations. Bursts of multiple population spikes were the
      most common responses in DBA mice and in younger animals, and repetitive single
      spikes were the predominant responses in C57 mice and in older animals. In all
      groups of animals, the average spontaneous discharge rate was highest after L
      glutamate perfusion, next highest after NMDA, and lowest after high K+ and
      hypoxia. The latency of the appearance of spontaneous epileptiform activity from
      CA1 region of hippocampal slices was long (> 2 min) after NMDA perfusion and
      short (< 1 min) after L-glutamate, high K+ and hypoxia. The duration of the
      increased spontaneous discharges was short (-1 min) after L-glutamate perfusion,
      long (> 3 min) after high K+ and hypoxia, and between short and long after NMDA
      perfusion. These results suggest that age and strain of animal and nature of
      stimulus precipitate different patterns of epileptiform activity in CNS.

PMID- 7821279
TI  - Palatal tremor of cortical origin presenting as epilepsia partialis continua.
AB  - Palatal tremor (PT) is frequently caused by brainstem lesions. The inferior olive
      plays a major role in the pathophysiologic mechanisms involved. We report a case
      of PT of cortical origin presenting as epilepsia partialis continua. EEG showed
      continuous left frontocentral epileptiform discharges and both single photon
      emission computed tomography (SPECT) and positron emission tomography (PET)
      showed focal hypoperfusion and hypometabolism in the corresponding location.

PMID- 7821280
TI  - Diffuse spike-wave status of 9-year duration without behavioral change or
      intellectual decline.
AB  - Continuous, generalized 2.5 to 3.5-Hz spike-wave (SW) discharges were evident in
      an EEG performed 13 h after a first seizure associated with a viral illness, in
      an 8-year-old girl. On eye opening, the EEG abnormality was suppressed and
      replaced by delta activity and brief spike-wave paroxysms. No alteration in
      consciousness and seizures or behavioral abnormalities accompanied the EEG
      findings. Based on the EEG, she was diagnosed as having "diffuse electrical
      status," the rare EEG phenomenon that occurs during wakefulness without
      associated behavioral changes. Although the child was completely normal
      clinically, the EEG findings persisted during a 9-year-follow-up period.
      Ethosuximide (ESM) 1 gr daily resulted in temporary disappearance of the
      bioelectrical status. During the last 2 years without medication the EEG finding
      tended to be restricted to the posterior regions.

PMID- 7821281
TI  - Serial FDG-PET scans in a patient with partial status epilepticus.

PMID- 7821282
TI  - Symposium of Risk Assessment of Urban Air: Emissions, Exposure, Risk
      Identification, and Risk Quantitation. Stockholm, Sweden, May 31-June 2, 1992.

PMID- 7821283
TI  - Physiologically based assessment of human exposure to urban air pollutants and
      its significance for public health risk evaluation.
AB  - Exact measurements or modeling of human exposures to environmental pollutants are
      of crucial importance for a realistic evaluation of public health risks. Current
      concepts, however, often use assumptions that result in overly conservative
      assessments of public health risks. Too frequently the dose of the pollutant
      retained in the body is approximated by oversimplified predictions assuming that
      all that is inhaled remains in the organism, that pollutant concentrations in
      various microenvironments are identical to those recorded by remote monitors,
      that the residence indicates the site where people spend all their time, and that
      the urban population is continuously exposed to outdoor air for 24 hr/day and 70
      years/lifetime. The review shows that in intermittent exposures only a fraction
      of inhaled toxicants remains in the body, that pollutant concentrations differ
      largely from one microenvironment to another, and that human activity patterns
      must be incorporated in every realistic exposure assessments. Specifically, the
      probability of being exposed to a short peak of ozone is predetermined in
      variable urban concentrations primarily by the coincidence of exercising outdoors
      at the time and site of elevated ozone levels. When combined with a
      physiologically based exposure evaluation, this probabilistic approach provides a
      scientifically sound estimate of actual occurrences of adverse exposures and a
      realistic assessment of potential health hazards.

PMID- 7821284
TI  - Mutagenic and carcinogenic significance and the possible induction of lung cancer
      by nitro aromatic hydrocarbons in particulate pollutants.
AB  - Studies of genotoxicity and carcinogenicity of nitro aromatic hydrocarbons focus
      on their high mutagenicity for bacteria and mammalian cells. Nitrobenzo[a]pyrenes
      (NBPs) and related nitroazaarenes also are extraordinarily mutagenic. 3-Nitro-6
      azabenzo[a]pyren-N-oxide was found to be a more potent mutagen than 1,8
      dinitropyrene. Mutagenicity of NBPs was associated with the position of
      substitution of the nitro function when nitrogen dioxide (NO2) was substituted at
      the third position on the benzo[a]pyrene (BP) structure, as in 3,6
      dinitrobenzo[a]pyrene but not in 1,6-diNBP. The NBPs were reduced by a rat liver
      postmitochondrial fraction to nitroso- and subsequently to amino-derivatives.
      Therefore, tumoral action in rats was induced at significant levels by
      subcutaneous injection of 3,6-diNBP, but no tumors were observed in rats given
      1,6-diNBP. Carcinogenic nitropyrenes were detected in the resected lung of a
      patient with lung cancer. It is suggested that the presence of nitropyrenes and
      the resulting tumor were due to exposure to by-products of combustion of heavy
      oil. The patient was a nonsmoker and farmer who had bred chickens for 40 years.
      He used heavy oil for heating the chicken house. Similarly, a group of Chinese
      people at high risk of developing lung cancer was selected to determine the
      initiator of lung cancer. Lung cancers were obtained from six Chinese female
      nonsmokers who were living in Fuyuan County, China. Polycyclic aromatic
      hydrocarbons were detected in resected lung specimens; they were
      benzo[k]fluoranthene, BP, benzo[g,h,i]perylene, and pyrene. These cases were
      associated with exposure to soot from combustion of coal usually used for heating
      and cooking indoors.

PMID- 7821285
TI  - Atmospheric chemistry of gas-phase polycyclic aromatic hydrocarbons: formation of
      atmospheric mutagens.
AB  - The atmospheric chemistry of the 2- to 4-ring polycyclic aromatic hydrocarbons
      (PAH), which exist mainly in the gas phase in the atmosphere, is discussed. The
      dominant loss process for the gas-phase PAH is by reaction with the hydroxyl
      radical, resulting in calculated lifetimes in the atmosphere of generally less
      than one day. The hydroxyl (OH) radical-initiated reactions and nitrate (NO3)
      radical-initiated reactions often lead to the formation of mutagenic nitro-PAH
      and other nitropolycyclic aromatic compounds, including nitrodibenzopyranones.
      These atmospheric reactions have a significant effect on ambient mutagenic
      activity, indicating that health risk assessments of combustion emissions should
      include atmospheric transformation products.

PMID- 7821286
TI  - Induction of mutation spectra by complex mixtures: approaches, problems, and
      possibilities.
AB  - More complex environmental mixtures have been evaluated for mutagenic activity at
      the hisD3052 allele of Salmonella, primarily in strain TA98, than in any other
      target or mutation assay. Using colony probe hybridization to detect a common hot
      spot deletion, followed by polymerase chain reaction and DNA sequencing, we have
      generated 10 mutation spectra from three classes of mixtures (i.e., urban air,
      cigarette smoke condensate, and municipal waste incinerator emissions). The
      mutation spectra are distinctly different among the three classes of mixtures;
      however, the spectra for samples within the same class of mixture are similar. In
      addition to the hot spot mutation, the mixtures induce complex mutations, which
      consist of a small deletion and a base substitution. These mutations suggest a
      mechanism involving misinsertion of a base opposite a DNA adduct followed by a
      slippage and mismatch. A role for DNA secondary structure also may be the basis
      for the mutational site specificity exhibited by the various mixtures. The
      results suggest that unique mutation spectra can be generated by different
      classes of complex mixtures and that such spectra are a consequence of the
      dominance of a particular chemical class or classes within the mixture. The
      problems associated with this type of research are discussed along with the
      potential value of mutation spectra as a tool for exposure and risk assessment.

PMID- 7821287
TI  - Mutations induced in the hypoxanthine phosphoribosyl transferase gene by three
      urban air pollutants: acetaldehyde, benzo[a]pyrene diolepoxide, and ethylene
      oxide.
AB  - Provisional mutational spectra at the hypoxanthine phosphoribosyl transferase
      (HPRT) locus in vitro have been worked out for acetaldehyde (AA) and
      benzo[a]pyrene diolepoxide (BPDE) in human (T)-lymphocytes and for ethylene oxide
      (EtO) in human diploid fibroblasts using Southern blotting and polymerase chain
      reaction (PCR)-based DNA sequencing techniques. The results indicate that large
      genomic deletions are the predominating hprt mutations caused by AA and EO,
      whereas BPDE induces point mutations that are mainly GC > TA transversions. The
      mutational spectra induced by the three agents are clearly different from the
      background spectrum in human T-cells. Thus, the hprt locus is a useful target for
      the study of chemical-specific mutational events that may help identify causes of
      background mutation in human cells in vivo.

PMID- 7821288
TI  - In vivo metabolism and genotoxic effects of nitrated polycyclic aromatic
      hydrocarbons.
AB  - During incomplete combustion of organic matter, nitro-polycyclic aromatic
      hydrocarbons (nitro-PAHs), are formed in a reaction that is catalyzed by a low
      pH. 2-Nitrofluorene (NF), a marker for nitro-PAHs, is metabolized in vivo by two
      different routes. After inhalation, potent mutagenic metabolites, hydroxylated
      nitrofluorenes (OH-NFs), are formed. The metabolites are distributed by systemic
      circulation. After oral administration, NF is reduced to the corresponding amine,
      a reaction mediated by the intestinal microflora. This metabolite is acetylated
      to 2-acetylaminofluorene (AAF), a potent carcinogen. Further ring-hydroxylation
      of AAF leads to detoxification and excretion. Induction of cytochrome P450s
      affects the metabolism, and more OH-NFs are formed. As a consequence, more
      mutagenic metabolites are found in the circulation. OH-NFs are excreted in the
      bile as, in terms of mutagenicity, totally harmless glucuronide conjugates. When
      these conjugates are excreted via the bile, intestinal beta-glucuronidase can
      liberate direct-acting mutagens in the intestine. Thus, inhalation of NF can lead
      to formation of potent mutagens in the intestine. NF is a direct-acting mutagen
      in bacterial assays and an initiator and promoter of the carcinogenic process,
      and gives rise to DNA adduct formation in laboratory animals.

PMID- 7821290
TI  - Is ambient ethene a cancer risk factor?
AB  - Ethene is, on a molar basis, a major urban air pollutant. It has been shown
      beyond doubt that a fraction of inhaled ethene is metabolized in mammals
      (including humans) via ethylene oxide, an electrophilic reagent that has been
      shown to be mutagenic and carcinogenic. To the extent that the linearity
      hypothesis for dose-response relationships at low levels is accepted, exposure to
      ethene is therefore expected to lead to a risk increment. In order to judge
      whether ethene as a single compound should be considered a risk factor, it has to
      be evaluated whether this risk increment is negligibly small or of concern to
      individuals or societies. The magnitude of the cancer risk from ethene cannot be
      inferred from animal experiments. Because of saturation of the metabolism of
      ethene, sufficient statistical power cannot be attained in long-term animal tests
      with about 100 animals per dose. By application of the radiation-dose equivalent
      of the unit of target dose of ethylene oxide and using the best (although still
      uncertain) value for the conversion factor (about 5%), exposure to 10 ppb ethene-
      a level occurring in urban areas--is expected to lead to a lifetime risk of
      cancer death amounting to approximately 70 per 100,000. According to a recent
      estimate the average exposure in Sweden to ethene is some six times lower. These
      figures are uncertain by a factor of at least three. They indicate ethene to be a
      risk factor of concern.

PMID- 7821289
TI  - Effects of induction and age-dependent enzyme expression on lung bioavailability,
      metabolism, and DNA binding of urban air particulate-absorbed benzo[a]pyrene, 2
      nitrofluorene, and 3-amino-1,4-dimethyl-5H-pyridol-(4,3)-indole.
AB  - The effect of interactions between urban air particulates (UAP) and carcinogens
      on bioavailability, metabolism, and DNA binding was studied in the isolated
      perfused and ventilated rat lung. The availability of benzo[a]pyrene (B[a]P)
      varied from 29 to 60% after intratracheal doses of carcinogen particulates
      dissolving extremely slow and fast, respectively. Several cytochrome P450 enzyme
      (P450) inducers acting as 2,3,7,8-tetrachlorodibenzo[p]dioxin-receptor ligands
      have been identified in UAP extracts. beta-Naphthoflavone (BNF) was used to study
      how P450 induction alters the lung metabolism of carcinogens. Pretreatment
      increased the lung clearance for B[a]P 8-fold and for 2-nitrofluorene (2NF) by a
      factor of four from 0.55 +/- 0.06 ml/min to 2.37 +/- 0.62 ml/min. Studies with
      the intact lung and with isolated lung cells show that carcinogen metabolism and
      pharmacokinetics depend both on the route of exposure and dosage and on the
      distribution of specific enzymes. A cytochrome P450IIB1 enzyme was detected in
      lung epithelial cells where it catalyzes 9-hydroxylation of 2NF. This rat lung
      2NF-9-hydroxylation capacity increases in parallel with the age dependent up
      regulation of lung P450IIB1 expression. Both human and rat lung tissue have the
      capacity to form 9-hydroxy-2-nitrofluorene (9-OH-2NF) that is mutagenic. A BNF
      inducible P450IA1 was detected in endothelial and alveolar type II cells.
      Consequently, aromatic hydroxylation dominated when 2NF was dosed directly into
      the lung circulation. Pretreatment of rats with BNF before intratracheal B[a]P
      dosage induced lung cytochrome P450IA1. The 7,8-dihydroxy-9,10-oxybenzo[a]pyrene
      deoxyguanosine adduct and the total lung DNA adduct levels increased
      significantly from a peak level of 75 +/- 8 to 151 +/- 19 fmole/mg DNA in lungs
      from control and BNF pretreated rats, respectively. 3-Amino-1,4-dimethyl-5H
      pyridol-(4,3)-indole (TRP-P1) is a potent mutagen and carcinogen identified in
      UAP extracts. Dietary BNF pretreatment of rats altered the [14C]TRP-P1
      distribution as analyzed by whole-body autoradiography. An enhanced retention was
      observed in the small intestine, forestomach, esophagus, and lung. UAP catalyzes
      oxygen radical formation and deoxyguanosine-8-hydroxylation, which were inhibited
      when the UAP samples were extracted with organic solvents or when they were
      incubated in the presence of desferroxamine. We therefore postulate that a
      polycyclic aromatic hydrocarbon autooxidation pathway may be responsible for
      generation of hydrogen peroxide, which may be further converted to hydroxyl
      radicals through an iron-dependent reaction.

PMID- 7821291
TI  - Stimulatory effects of sulfur and nitrogen oxides on carcinogen activation in
      human polymorphonuclear leukocytes.
AB  - The occurrence of inflammatory processes and of cancer in the human respiratory
      tract is intimately associated. One of the major factors in this is probably the
      recruitment of and stimulated activity of polymorphonuclear leukocytes (PML) in
      conjunction with the ability of these cells to convert various carcinogens to
      their ultimate active metabolites. In this study, we demonstrate that nitrite and
      sulfite, the major dissolution products of the environmental pollutants nitrogen
      dioxide and sulfur dioxide in water enhance the metabolic activation of trans-7,8
      dihydroxy-7,8-dihydrobenzo[a]pyrene (BP-7,8-dihydrodiol), the proximal carcinogen
      of benzo[a]pyrene, to trans-7,8-dihydroxy-9,10-epoxy-7,8,9,10
      tetrahydrobenzo[a]pyrene (BPDE) and tetraols, the corresponding hydrolysis
      products, in human PML prestimulated with 12-O-tetradecanoylphorbol-13-acetate.
      Nitrite was more efficient than sulfite in stimulating the formation of reactive
      intermediates of BP-7,8-dihydrodiol in PML that covalently bind to extracellular
      DNA and, in particular, to intracellular proteins. The mechanism by which sulfite
      stimulates the metabolism of BP-7,8-dihydrodiol most probably involves the
      intermediate formation of a sulfur trioxide radical anion (SO3.-) the subsequent
      formation of the corresponding sulfur peroxyl radical anion (.OOSO3-) in the
      presence of oxygen. The mechanism underlying the stimulatory action of nitrite is
      less clear but the major pathway seems to involve myeloperoxidase. These results
      offer an explanation for the increased incidence of lung cancer in cigarette
      smokers living in urban areas. The major glutathione transferase (GST) isoenzyme
      in human PML is GST P1-1, a Pi-class form. The GST activity of PML was found to
      be inversely correlated with the extent of binding of BP-7,8-dihydrodiol products
      to exogenous DNA. These results suggest that individuals exhibiting high GST
      activity in the PML may be better protected against the type of carcinogenic
      dealt with in this study.

PMID- 7821293
TI  - Use of quantitative epidemiologic data in regulatory approaches to air pollution.
AB  - Ambient air is a complex mixture containing a variety of substances, some of
      which are known to be carcinogenic. To develop a homogeneous approach for
      regulating the emission of these compounds, their individual carcinogenic
      potential needs to be placed on a comparable scale. The unit risk may be
      considered as an appropriate measure that condensates dose-response analyses of
      epidemiologic data into a single, easily interpretable estimate. Given the
      information on the carcinogenic potency of single compounds, more information on
      the occurrence of the components and the relation of emissions to specific
      emittents needs to be considered. In Germany, an approach has been developed that
      combines different assumptions on complex mixtures for the regulation of the
      overall risk. This paper outlines some of the principal aspects of the underlying
      concepts.

PMID- 7821292
TI  - On cancer risk estimation of urban air pollution.
AB  - The usefulness of data from various sources for a cancer risk estimation of urban
      air pollution is discussed. Considering the irreversibility of initiations, a
      multiplicative model is preferred for solid tumors. As has been concluded for
      exposure to ionizing radiation, the multiplicative model, in comparison with the
      additive model, predicts a relatively larger number of cases at high ages, with
      enhanced underestimation of risks by short follow-up times in disease
      epidemiological studies. For related reasons, the extrapolation of risk from
      animal tests on the basis of daily absorbed dose per kilogram body weight or per
      square meter surface area without considering differences in life span may lead
      to an underestimation, and agreements with epidemiologically determined values
      may be fortuitous. Considering these possibilities, the most likely lifetime
      risks of cancer death at the average exposure levels in Sweden were estimated for
      certain pollution fractions or indicator compounds in urban air. The risks amount
      to approximately 50 deaths per 100,000 for inhaled particulate organic material
      (POM), with a contribution from ingested POM about three times larger, and
      alkenes, and butadiene cause 20 deaths, respectively, per 100,000 individuals.
      Also, benzene and formaldehyde are expected to be associated with considerable
      risk increments. Comparative potency methods were applied for POM and alkenes.
      Due to incompleteness of the list of compounds considered and the uncertainties
      of the above estimates, the total risk calculation from urban air has not been
      attempted here.

PMID- 7821294
TI  - Human exposure to urban air pollution.
AB  - This study deals with some methods of making human exposure estimates, aimed at
      describing the human exposure for selected air pollutants in Sweden that are
      suspected carcinogens. Nitrogen oxides (NOx) have been chosen as an indicator
      substance for estimating the concentration of the urban plume. Earlier
      investigations have shown that the traffic in Swedish cities contributes around
      85% to the measured NOx concentrations, and that most of the mutagenicity in
      urban air originates from traffic. The first section of this paper describes
      measurements in Stockholm of some unregulated light hydrocarbons, such as ethene,
      ethyne, propane, propene, butane, and isobutane. In addition, measurements of
      some volatile aromatic hydrocarbons are presented. Simultaneous measurements of
      carbon monoxide (CO) were made. The ratios between CO and the individual specific
      compounds were determined by linear regression analysis. By analysis of
      relationships between CO and NOx, NOx concentrations can be used as a tracer to
      describe the exposure for these specific compounds. NOx are considered to be a
      better tracer than CO, because NOx or NO2 values exist for many places over a
      long time, while CO is measured mostly in streets with high concentrations. At
      low concentrations, instruments that measure normal CO levels give no detectable
      signals. Through use of atmospheric dispersion models and models that describe
      how people live and work in urban areas it has been possible to describe the
      average exposure to NOx in cities of different sizes. The exposure to NOx for
      people living in the countryside has also been estimated. In this way, it has
      been possible to calculate the average exposure dose for NOx for the Swedish
      population. This figure is 23 micrograms/m3. By use of the relationships between
      NOx and specific compounds the average dose has been calculated for the following
      compounds: polyaromatic compounds (PAH); ethene, propene, and butadiene; benzene,
      toluene, and xylene; formaldehyde and actaldehyde; nickel, chromium (VI),
      arsenic, and cadmium; asbestos; and silicon.

PMID- 7821295
TI  - Urban air pollution by carcinogenic and genotoxic polyaromatic hydrocarbons in
      the former USSR.
AB  - The content of major carcinogenic and genotoxic polyaromatic hydrocarbons (PAH)
      in urban air, vehicle, and industrial emissions is assessed. A sensitive,
      specific, and selective method for PAH and nitro-PAH quantitation was developed
      on the basis of low-temperature luminescence-spectra of frozen polycrystalline
      solutions. Polyarene contents in urban air and urban industrial emissions, as
      well as vehicle exhausts, are compared to the Russian Ministry of Health standard
      of maximal permissible concentration for benzo[a]pyrene in the ambient air.
      Special attention was paid to the study of PAH profiles and characteristics of
      different sources. The feasibility of using benzo[a]pyrene to assess PAH content
      in industrial and vehicle emissions was explored. PAH profiles in the ambient air
      and local emissions are compared. In addition, genotoxicity of the emissions of
      coke plant and diesel engine exhausts are compared to their polyarene content.

PMID- 7821296
TI  - The air quality in Danish urban areas.
AB  - The Danish air pollution abatement is based by and large on emission control.
      Since the ratification of the international sulfur protocol of 1985, there has
      been a continuous tightening of the permissible sulfur content in fuels and of
      the maximum emissions from power plants. As a consequence, the total annual
      emission of sulfur dioxide (SO2) has been reduced from 450,000 tons in the
      seventies to 180,000 tons in 1990. This has had a pronounced effect on the SO2
      levels in Danish urban areas. Thus, in Copenhagen, the yearly averages have
      fallen to about 25%. For nitrogen oxides emitted from the power plants, similar
      regulations are in force. With this legislation, the most important and crucial
      source of air pollution in Danish urban areas is road traffic. The contribution
      of nitrogen oxides from national traffic accounts for nearly half the total
      Danish emission and is increasing steadily; this is consistent with an observed
      increase of nitrogen oxides in ambient air. The permissible levels of lead in
      petrol has been reduced drastically. After an introduction of reduced tax on lead
      free petrol, it now accounts for more than two-thirds of the total consumption.
      As a result, the concentration of lead in urban ambient air has been reduced to
      less than one-sixth. The introduction of 3-way catalytic converters from October
      1990 will result in reductions in the emission of a series of pollutants, e.g.,
      lead, volatile organic compounds, carbon monoxide, and nitrogen oxides. In 1980,
      a Danish air quality monitoring program was established as a cooperative effort
      between the authorities, the Government, the countries, the municipalities, and
      the Greater Copenhagen Council.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7821297
TI  - Ambient air pollutants in upper Silesia: partial chemical composition and
      biological activity.
AB  - The air monitoring system in Upper Silesia has provided abundant data on airborne
      pollutants. Air quality in this region is bad: a concentration of several gases,
      volatile compounds, metals, and complex mixtures of organic compounds carried by
      small particulate matter exceeds both daily and yearly admissible levels. About
      250 individual polycyclic aromatic hydrocarbonds (PAHs) were identified in
      airborne pollutants, and hundreds of not identified compounds are seen on gas
      chromatographic profiles as minor peaks. Among PAHs are present compounds with
      known carcinogenic potency for humans. Seasonal variation with distinctly lower
      concentration of pollutants in summer than in winter was noticed. Fifteen PAHs
      including benzo[a]pyrene (B[a]P) determined by GC-MS method in 20 measuring
      points showed constant relative proportions. Thus B[a]P could be used as a
      representative compound for other PAHs. In urban areas, a core of Silesia values
      for B[a]P concentration ranged from 60 to 90 ng/m3 in winter to 5 to 20
      micrograms/m in summer. Mutagenicity tested on Salmonella strains showed seasonal
      variation with distinctly higher values in winter. Environmentally exposed humans
      showed a higher level of PAH-DNA adducts in WBC than the control population from
      rural area. Total organic extract of small particulate matter exhibited both
      direct and indirect mutagenic activity, induced formation of micronuclei in bone
      marrow cells of BALB/c mice, induced chromosomal rearrangements, and increased
      sister chromatid exchange index.

PMID- 7821298
TI  - Chemical and mutagenic patterns of airborne particulate matter collected in 17
      Italian towns.
AB  - The mutagenicity of airborne particulate matter collected in 17 towns of Italy in
      1990 was assessed using the Ames test. The mutagenicity of crude extract
      correlated with amount of lead, suggesting the direct contribution of gasoline
      car exhausts. Moreover, the mutagenicity correlated with particulate matter
      amounts. An inverse correlation with temperature was observed. The crude extracts
      were fractionated in acid, basic, and neutral fractions. The latter was further
      separated into polycyclic aromatic hydrocarbon (PAH), polar, and nonpolar
      fractions. Acid and polar fractions showed the higher mutagenicity. Average
      recovery of mutagenicity was about 60%.

PMID- 7821299
TI  - Kinetics of tumour necrosis factor-alpha, soluble tumour necrosis factor
      receptors, interleukin 1-beta and its receptor antagonist during serious
      infections.
AB  - Tumour necrosis factor-alpha (TNF) and interleukin-1 beta (IL-1 beta) are the
      central mediators in the genesis of sepsis. The proinflammatory effects of these
      cytokines are counteracted in vivo by natural inhibitors. Soluble TNF receptors
      (sTNFR) are shed upon inflammatory stimuli such as IL-1 beta and TNF itself.
      Circulating TNF can be complexed by these receptors, thus preventing TNF from
      binding to effector cells. The binding of IL-1 beta to its receptor can be
      blocked by high concentrations of interleukin-1 receptor antagonist (IL-1Ra),
      which is produced and released upon nearly the same stimuli as IL-1 beta. This
      review presents some aspects of the kinetic behaviour of native sTNFR and of the
      production of native IL-1Ra during severe infections. It appears that in
      fulminant septicaemia, the plasma concentration of TNF is increased only
      transiently, during the very early stage of the infection. The concentration of
      sTNFR, in contrast, remains elevated much longer, probably due to a slower
      clearance. During the acute stage of severe infectious diseases, peripheral blood
      cells cannot be stimulated to produce IL-1 beta. The production of IL-1 Ra, in
      contrast, is not affected. Thus, the kinetic behaviour and regulation of TNF and
      IL-1 beta, is different from that of their antiinflammatory counterparts.

PMID- 7821300
TI  - Origin and impact of plasmid-mediated extended-spectrum beta-lactamases.
AB  - Resistance to oxyimino cephalosporins was originally highlighted by the emergence
      of plasmid-encoded extended-spectrum beta-lactamases deriving by mutation from
      TEM-1, TEM-2 and SHV type enzymes (class A). The broader spectrum of resistance
      produced by these enzymes is related to more amino acid substitutions, but
      susceptibility to seven alpha-methoxyimino cephalosporins and carbapenems was
      preserved until recently. Clavulanate-sensitive extended-spectrum beta-lactamases
      are distributed worldwide, mainly among Klebsiella pneumoniae isolates. Novel
      clavulanate-sensitive extended-spectrum beta-lactamases deriving from other class
      A enzymes (e.g. MEN-1 from beta la OXY, OXA-11 in Pseudomonas aeruginosa from PSE
      2) have been reported. Recently, clavulanate-resistant extended-spectrum beta
      lactamases (class C) were encountered amongst single isolates, mostly Klebsiella
      pneumoniae. These cephalosporinases or cefamycinases (usually chromosomally
      mediated) have expanded the spectrum of plasmid-encoded resistance to include
      seven alpha-methoxyimino cephalosporins. Thus far, only two isolates (1
      Pseudomonas aeruginosa, 1 Bacteroides fragilis), both recovered in Japan, with
      plasmid-mediated resistance to carbapenems have been found.

PMID- 7821301
TI  - Genetics of extended-spectrum beta-lactamases.
AB  - Bacteria have adapted to the introduction of aztreonam, cefotaxime, ceftazidime,
      ceftriaxone and other oxyimino-beta-lactams by altering existing plasmid-mediated
      class A and class D beta-lactamases so as to expand their spectrum of activity.
      In the TEM and SHV families of extended-spectrum beta-lactamases, relative
      activity toward oxyimino-substrates increases with the number of amino acid
      substitutions but at the price of lowered intrinsic efficiency, so that
      compensatory up-promoter events are often associated with increased enzyme
      expression. Another new mechanism of resistance is the capture on plasmids of
      normally chromosomal genes from Enterobacter cloacae, Citrobacter freundii or
      Pseudomonas aeruginosa, which upon transfer can provide Klebsiella pneumoniae or
      Escherichia coli with resistance to alpha-methoxy-beta-lactams, such as cefoxitin
      or cefotetan, as well as to oxyimino-beta-lactams.

PMID- 7821302
TI  - Risk factors for acquisition of multiply drug-resistant gram-negative bacteria.
AB  - Some bacteria are naturally resistant to many antibiotics and most can become
      multiply resistant. Multiply resistant gram-negative bacteria have proved a
      particular problem over the last 30 years, but the development of new agents has
      lessened their significance for most clinicians. Now, however, clinical practice
      is threatened by the lack of new classes of antibiotics, the widespread emergence
      of resistance and the advent of plasmid-mediated cephalosporinases by which the
      spread of resistance is likely to be rapid. Increased use of prophylaxis in
      immunosuppressed and intensive care patients is likely to aggravate the problem,
      as is the use of new broad-spectrum agents in the community. More directed and
      restricted antibiotic use and better education of patients and prescriber are
      necessary to contain the problem of antibiotic resistance. Improved surveillance
      of sensitivity trends is essential. Many outbreaks also are associated with poor
      infection control techniques. The cost of outbreaks due to multiply resistant
      organisms and lack of compliance with infection control procedures needs to be
      properly studied. While many predisposing factors for the acquisition of these
      organisms and the development of infection are understood, the multifactorial
      nature of illness in many patients complicates the issue, necessitating further
      study of risk factors and preventative and therapeutic measures.

PMID- 7821303
TI  - Clinical significance of extended-spectrum beta-lactamases.
AB  - Extended-spectrum beta-lactamases (ESBLs) have now been described in many
      hospitals worldwide. While they have been detected in many pathogenic gram
      negative bacteria, they are particularly prevalent in Klebsiella isolates. Known
      risk factors for colonization and/or infection with organisms harboring these
      enzymes include admission to an intensive care unit, recent surgery,
      instrumentation, prolonged hospital stay and antibiotic exposure, especially
      exposure to extended-spectrum beta-lactam agents. In this report three recent
      epidemics from the USA will be described in which the role of selective
      antibiotic pressure seems clear. Data from two hospital epidemics, one from New
      York and another from Stanford, California, will be reviewed briefly. In
      addition, recent studies describing the spread of extended-spectrum beta
      lactamases among nursing home patients in Chicago, Illinois, will be outlined.
      The limited data available on treatment options for patients infected with ESBL
      containing strains will be reviewed, focusing on the activity of
      piperacillin/tazobactam and imipenem against these otherwise broadly resistant
      strains. Lastly, attempts to control these organisms, including infection control
      measures and selective bowel decontamination, will be reviewed.

PMID- 7821304
TI  - Differential antibiotic-induced release of endotoxin from gram-negative bacteria.
AB  - Treatment of log phase cultures of Escherichia coli with cell wall active
      antibiotics results in increased exposure of immunologically reactive lipid A
      epitopes of lipopolysaccharide (LPS) and release of soluble LPS into culture
      supernatants. Comparison of the efficacy of two cell wall active antibiotics,
      ceftazidime, a penicillin-binding protein 3 selective antibiotic, and imipenem, a
      penicillin-binding protein 2 selective antibiotic, for their relative efficacy in
      mediating LPS release indicated quantitative but not qualitative differences,
      with the former antibiotic manifesting a significantly broader range of
      concentrations at which LPS release could be demonstrated. Comparison of the
      relative efficacy of these two antibiotics in a mouse bacteraemia model in which
      animals were made hypersensitive to the lethal effects of endotoxin by treatment
      with D-galactosamine indicated that the latter antibiotic may provide a greater
      level of protection. These studies suggest that the release of endotoxin mediated
      by antibiotic treatment may contribute to the pathogenesis of disease in
      infectious due to gram-negative organisms.

PMID- 7821306
TI  - Prevention of coronary heart disease in clinical practice. Recommendations of the
      Task Force of the European Society of Cardiology, European Atherosclerosis
      Society and European Society of Hypertension.

PMID- 7821305
TI  - Haemostatic factors and prevalent coronary heart disease; the FINRISK Haemostasis
      Study.
AB  - We examined the association of haemostatic factors with prevalent coronary heart
      disease (CHD) in the population-based FINRISK Haemostasis Study. Of the 2365
      participants aged 45-64 years, 88 men and 44 women with prevalent CHD were
      identified. The participants with CHD were older and had lower high density
      lipoprotein cholesterol, higher triglycerides and higher body mass index than the
      participants without CHD. Men with CHD had significantly higher plasma fibrinogen
      (P < 0.0001, adjusted for age and smoking) and lipoprotein (a) (Lp (a), P =
      0.001, adjusted for age) concentrations than those without CHD. Among women, the
      findings were consistent with those of men, but only fibrinogen reached the
      conventional level of statistical significance (P = 0.04). No difference was
      observed in factor VII antigen, factor VII activity or in plasminogen. The
      association of Lp (a) with prevalent CHD was dependent on fibrinogen
      concentration (P = 0.02 for the interaction-term) and on non-HDL cholesterol
      concentration (P = 0.01 for the interaction-term). These cross-sectional results
      do not prove causality, but they demonstrate a considerable accumulation of
      prevalent CHD among persons with high Lp (a), fibrinogen and non-HDL cholesterol.

PMID- 7821307
TI  - Report of the ESC Task Force on Digital Imaging in Cardiology. Recommendations
      for digital imaging in angiocardiography.

PMID- 7821308
TI  - Mitral to aortic velocity-time integral ratio. A non-geometric pulsed-Doppler
      regurgitant index in isolated pure mitral regurgitation.
AB  - To determine the clinical value of a simple and non-geometric pulsed Doppler
      regurgitant index, namely the mitral to aortic velocity-time integral (VTI) ratio
      in the semiquantitative assessment of severity of isolated pure mitral
      regurgitation (MR), 109 patients with isolated pure MR and sinus rhythm
      prospectively underwent Doppler echocardiography within 48 h of cardiac
      catheterization. The eccentricity of regurgitant jets was assessed by Doppler
      colour flow imaging and the mitral and aortic VTI and its ratio were derived from
      the pulsed Doppler method. Angiographic grade of MR was evaluated in all patients
      with MR, but haemodynamic regurgitant fraction was determined in only 91
      patients. Fifty patients in sinus rhythm and without valvular disease served as
      controls. In the control group, the mitral VTI (16.2 +/- 2.5 cm) was lower than
      the aortic VTI (20.6 +/- 2.8 cm) (P < 0.001), resulting in a mitral to aortic VTI
      ratio of 0.79 +/- 0.08. In patients with MR, the mitral VTI was significantly
      greater than the aortic VTI (23.1 +/- 6.8 vs 16.9 +/- 4.7 cm, P < 0.001). There
      was a close relationship between the mitral to aortic VTI ratio and the
      angiographic grading of MR (n = 109, r = 0.74, P < 0.001). A ratio > or = 1.3
      classified patients with severe MR (grade III or IV) with a sensitivity of 87%, a
      specificity of 91%, and positive and negative predictive values of 93% and 84%,
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7821309
TI  - Volume loading in predominant right ventricular infarction: bedside haemodynamics
      using rapid response thermistors.
AB  - Intravenous fluid loading is commonly used for the treatment of low cardiac
      output (CO) syndrome complicating severe right ventricular infarction (RVMI). We
      prospectively evaluated the effectiveness of this method in 11 consecutive
      patients (age 66 +/- 14 years) with severe RVMI, using a newer thermodilution
      method with rapid response thermistors. Volume loading was performed until
      pulmonary wedge pressure (PWP) reached 18 to 24 mmHg. Right atrial pressure
      (RAP), pressures of the right ventricle (RV) and pulmonary artery (PA), PWP, RV
      volumes, RV ejection fraction (RVEF), stroke volume (SV), CO, pulmonary vascular
      resistance (PVR) and RAP/PWP ratio were measured before and after volume loading.
      RAP rose from 12 +/- 4 to 19 +/- 5 mmHg (P < 0.0001) and its tracing showed a non
      compliant pattern in all patients. RV end-diastolic pressure rose from 13 +/- 4
      to 20 +/- 5 mmHg (P < 0.0001) and PWP from 14 +/- 3 to 20 +/- 6 mmHg (P <
      0.0001). Mean PA pressure rose from 20 +/- 3 to reach 25 +/- 6 mmHg (P < 0.001),
      while PVR did not change significantly (117 +/- 39 vs 101 +/- 49 dyn.s.cm-5, P
      ns). RAP/PWP ratio rose from 0.85 +/- 0.14 to 1.05 +/- 0.07 (P < 0.01). The end
      diastolic RV volume increased from 95 +/- 26 to 113 +/- 24 ml.m-2 (P < 0.001);
      however, RV end-systolic volume increased from 65 +/- 28 to 83 +/- 29 ml.m-2 (P <
      0.01), thus SV did not change significantly (30 +/- 6 vs 30 +/- 8 ml.beat-1.m-2,
      P ns). RVEF decreased from 32 +/- 11 to 28 +/- 11% (P < 0.001). CO did not
      improve significantly (2.3 +/- 0.42 vs 2.4 +/- 0.62 l.min-1.m-2, P ns) neither
      did the clinical status.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7821311
TI  - Microalbumin excretion in patients with positive exercise electrocardiogram
      tests.
AB  - Thirty-three subjects underwent exercise electrocardiogram testing, 20 had a
      history of myocardial infarction and 13 were age-matched volunteers. Exercise
      electrocardiograms were positive in 15 subjects, negative in 12 and anomalous in
      six. Urinary microalbumin excretion was measured at rest, 30 and 60 min after
      exercise. Urinary microalbumin excretion was expressed as the albumin-creatinine
      ratio in mg.mmol-1. In the positive exercise electrocardiogram group median
      albumin-creatinine ratio increased from 1.0 mg.mmol-1 (95% CI 0.94-1.49) at rest
      to 2.0 mg.mmol-1 (95% CI 1.51-3.94) 30 min after exercise, whilst in the negative
      electrocardiogram group median resting and 30 min post exercise albumin
      creatinine ratio values of 0.85 (95% CI 0.53-1.32) and 1.80 (95% CI 0.63-2.32)
      mg.mmol-1 respectively were not significantly different. These results suggest
      that exercise-induced myocardial ischaemia is associated with increased urinary
      microalbumin excretion.

PMID- 7821310
TI  - Comparison between the effect of L-propionylcarnitine, L-acetylcarnitine and
      nitroglycerin in chronic peripheral arterial disease: a haemodynamic double blind
      echo-Doppler study.
AB  - The haemodynamic effects on the peripheral vascular bed of L-acetylcarnitine, L
      propionylcarnitine, and nitroglycerin were tested by echo-Doppler in a double
      blind cross-over study. Eleven male patients suffering from peripheral arterial
      obliterative disease (PAOD) in the second stage of Fontaine's classification, and
      11 matched control subjects were enrolled in the study. Each subject received one
      of three different treatments on each day of the study in a different order
      following a random assignment. The treatments were either 30 mg x kg of L
      acetylcarnitine (LAC) or 30 mg x kg of L-propionylcarnitine (LPC) or
      nitroglycerin (NTG) 1.25 mg given as a single i.v. bolus injected over 3 min.
      Echo-Doppler measurements of blood flow velocity, and cross-sectional area of the
      femoral artery were performed at baseline and 10, 20, and 30 min after injection
      of the drugs. Pulsatility Index (an index derived from the blood flow velocity
      and related to vascular resistance: PI = Vmax - Vmin/Vmean) was also obtained
      each time. Results were analysed using a Student's t-test for paired data. L
      acetylcarnitine and L-propionylcarnitine showed no haemodynamic effects in either
      group of subjects (controls and PAOD patients) whether blood flow or vascular
      resistance was considered. There were haemodynamic changes (a decrease in blood
      flow velocity and an increase in arterial systemic resistance) only after NTG
      administration. The changes were more evident in controls than in PAOD patients.
      Femoral artery cross-sectional area showed no statistically significant effect as
      regards treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7821312
TI  - Impact of infarct artery patency on the relationship between electrocardiographic
      and ventriculographic evidence of acute myocardial ischaemia.
AB  - Routine invasive evaluations are being abandoned, and thus simple non-invasive
      methods for estimating the extent of jeopardized myocardium during evolving
      myocardial infarction are needed for risk stratification to guide the appropriate
      therapeutic intervention. With this in mind the aim of the paper was to evaluate
      the association between ischaemic changes in the standard electrocardiogram and
      the function of acutely infarcted myocardium in relation to infarct artery
      patency status. Forty consecutive patients with a first acute myocardial
      infarction, admitted within 6 h of symptom onset and without bundle branch or
      fascicular block were included. Summated ST segment elevation in 11
      electrocardiographic leads (aVR excluded) was measured to the nearest 0.05 mV and
      compared to regional wall motion, estimated by the centreline method (SD/chord)
      and global left ventricular ejection fraction (% LVEF) after thrombolytic
      therapy. Acute angiographic and ST segment measurements were performed at a
      median 254 min (range 70-485) after the onset of symptoms. Patients were grouped
      according to infarct artery patency status after intravenous thrombolysis. Of the
      40 patients, 27 had a patent (Thrombolysis In Acute Myocardial Infarction trial
      (TIMI) grade 2-3 flow) and 13 had persistently occluded (TIMI 0-1 flow) infarct
      arteries. Anterior myocardial infarction was present in 13 and seven patients in
      the two groups. In the TIMI 2-3 group, the summated ST elevation did not
      correlate with % LVEF or SD/chord (rs = -0.08; and rs = -0.17, respectively). In
      the TIMI0-1 group the summated ST elevation correlated inversely with both % LVEF
      and SD/chord (rs = -0.70; and rs = -0.56, respectively).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7821313
TI  - Effects of intensive exercise training on lipid levels in high risk post-MI
      patients.
AB  - One hundred and two patients participated in a 4 week programme of intensive
      exercise training early after myocardial infarction. Lipid levels were measured
      before and after exercise training. The mean exercise capacity increased by 49%
      (P = 0.0001). Twenty-one patients who continued smoking and 25 non-beta-blocked
      patients were considered to have an increased risk of recurrent cardiac events,
      as were patients with high initial lipid levels. In the smokers and non-beta
      blocked patients total cholesterol decreased by 0.30 mmol.l-1 (P = 0.031) and
      0.37 mmol.l-1 (P = 0.042) respectively and triglycerides by 0.28 mmol.l-1 (P =
      0.058) and 0.13 mmol.l-1 (P = 0.11). Patients with high initial cholesterol and
      triglyceride levels had the largest cholesterol and triglyceride decrease, r =
      0.43 (P = 0.0001) and r = 0.38 (P = 0.001) respectively. After adjusting for
      initial lipid levels, cholesterol (P = 0.036) as well as triglycerides (P =
      0.034) decreased in patients without beta-blocker treatment whereas smoking no
      longer had an independent effect on lipid level decrease. HDL-cholesterol did not
      change in any group. Thus, after 4 weeks of exercise training lipid profiles were
      improved in patients with an increased risk of recurrent cardiac events. Beta
      blocker treatment, however, seemed to hinder the beneficial effects of exercise
      training on lipid levels.

PMID- 7821314
TI  - Long-term effect of cardioversion on peak oxygen consumption in chronic atrial
      fibrillation. A 2-year follow-up.
AB  - Restoration of sinus rhythm may improve functional capacity in atrial
      fibrillation in the short-term. Little is known, however, about its long-term
      effect on functional status. The aim of the present study was to evaluate the
      long-term effect of cardioversion on peak oxygen consumption (VO2) in patients
      with chronic atrial fibrillation. Patients with such a condition and due to
      undergo electrical cardioversion were eligible for the study. Patients underwent
      treadmill exercise testing with measurement of peak VO2 before cardioversion, and
      at 1 month and 2 years thereafter. Based on the rhythm present at those times
      after cardioversion, patients were categorized into three groups: those in sinus
      rhythm after 1 month and 2 years (Group I); those in sinus rhythm after 1 month,
      but with atrial fibrillation after 2 years (Group II); and those who were in
      atrial fibrillation both at 1 month and 2 years following cardioversion (Group
      III). Thirty-nine patients were included, and underlying heart disease was
      present in 24 of them (62%). In the comparison of the baseline characteristics of
      Group I (n = 17), Group II (n = 11), and Group III (n = 11), underlying heart
      disease was more frequent in Group I (88%, 45%, and 36%, respectively); otherwise
      they were similar. In Group I, peak VO2 showed an insignificant increase from
      21.1 +/- 5.0 to 22.3 +/- 5.0 ml.min-1.kg-1 month after. cardioversion. After 2
      years of sinus rhythm, peak VO2 showed a further increase to 23.8 +/- 5.0 ml.min
      1.kg-1 (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7821315
TI  - Systemic embolism in aortic arch atheromatosis.
AB  - The role of aortic atheromatosis as a risk factor for systemic embolism and its
      relationship to other potential sources of embolism was examined in 335 patients
      undergoing transoesophageal echocardiography for various clinical reasons.
      Multiple logistic regression analysis revealed a significant correlation between
      embolism and moderate (atheroma protruding less than 5 mm into the aortic lumen,
      grade 2) to complex (atheroma protruding at least 5 mm into the vessel lumen with
      or without mobile components, grade 3) atherosclerosis of the aortic arch. Odds
      ratios were 4.0 for grade 2 atheromatosis (95% CI 1.1-14.4; P < 0.05) and 9.7 for
      grade 3 atheromatosis (95% CI 1.5-61.0; P < 0.05). Other significant associations
      were found with cardiac thrombi (odds ratio 4.0, 95% CI 1.7-9.3; P < 0.005) and
      hypertension (odds ratio 1.8, 95% CI 1.0-3.3; P < 0.05). In a subset of 163
      patients in whom results of an ultrasound examination were available,
      atherosclerosis of the carotid arteries was another significant marker of
      embolism (odds ratio 2.0, 95% CI 1.2-3.3; P < 0.01). In conclusion, aortic arch
      atheromatosis, which was predominantly recognized in patients with
      cerebrovascular events of undetermined cause, seems to carry a risk of embolism
      that is comparable to cardiac and carotid atherosclerosis.

PMID- 7821316
TI  - Peri-operative complications following surgical closure of atrial septal defect
      type II in 232 patients--a baseline study.
AB  - This study intends to provide a detailed overview of the types and rates of peri
      operative complications after surgical correction of an isolated ASD II. The
      transvenous approach to the occlusion of atrial septal defects has yielded
      promising results during its first 5 years of clinical trials, but before it can
      be established as a routine measure, definite proof is needed to demonstrate that
      its rate of serious complications does at least not exceed that of the surgical
      closure. Between 1985 and 1992, 232 consecutive patients underwent surgical
      closure of a secundum atrial septal defect. Among the patients 118 were children
      (< 18 years; 79 girls and 39 boys) with a mean age of 8.9 +/- 5.2 years (4 months
      17 years) and 114 adults (74 women and 40 men) with a mean age of 28.5 +/- 10.8
      years (18-69 years). Pre-operatively eight children (6.8%) and eight adults (7%)
      were treated for right heart failure. Mean pulmonary artery pressure was 20.4 +/-
      10.4 mmHg for the children and 19.3 +/- 7 mmHg for the adults. The average
      pulmonary artery to systemic flow ratios were 2.9:1 and 3:1 for children and
      adults, respectively. Thirty children (25.4%) and 15 adults (13.2%) underwent
      patch closure while direct suture was the method used for the remaining patients.
      Average cardiopulmonary bypass time was 35.7 +/- 17.9 min for the children and
      41.5 +/- 19.9 min for the adults. The length of the procedure (skin to skin) was
      a mean of 116 min in the young group, and 141 min in the adult group.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7821317
TI  - Implications of ST changes in reperfusion management of acute inferior myocardial
      infarction.
AB  - ST elevation is the basis of management decisions in acute myocardial infarction
      and may provide a quick means of stratifying patients. This is particularly
      relevant with inferior infarction because of the generally smaller benefit-to
      risk ratio of reperfusion therapy. We studied the relationship between ST changes
      and the perfusion territory of the infarct-related artery in 95 patients: 77 with
      proximal right coronary related infarction (perfusion territory quantitated by an
      angiographic score maximum possible value = 1.0) and 18 with circumflex related
      infarction (divided angiographically into proximal and distal arterial
      occlusions). For right coronary related infarction, the angiographic score ranged
      widely from 0.25 to 0.82 (mean 0.53, standard deviation 0.13). Parameters that
      correlated with the angiographic score on univariate analysis were precordial ST
      depression (r = -0.59), inferior ST elevation (r = 0.51), and number of leads
      with ST change (r = 0.56). On multivariate analysis, only precordial ST
      depression and the number of leads with ST elevation were independent predictors
      of the angiographic score (r = 0.64), with precordial ST depression predicting
      the major portion of its variability. For circumflex related infarction,
      precordial ST depression was the only predictor of a proximal occlusion. Summed
      precordial ST depression > or = 0.3 mV, as compared to less or no ST depression,
      predicted a larger territory of the infarct-related artery (either a right
      coronary angiographic score >0.5 or a proximal left circumflex lesion, kappa =
      0.51, P < 0.001). In acute inferior infarction, deep precordial ST depression
      reflects large jeopardized territory, a subgroup that may benefit more from
      aggressive reperfusion.

PMID- 7821318
TI  - Changes of QRS axis in transient myocardial ischaemia induced by percutaneous
      transluminal coronary angioplasty.
AB  - The QRS axis of 130 consecutive patients with coronary artery disease undergoing
      percutaneous transluminal coronary angioplasty (PTCA) were measured before
      balloon inflation and just before balloon deflation. Patients were divided into
      two groups. Group A (103) had angina pectoris and/or non-transmural old
      myocardial infarction with no abnormal Q waves; group B (27) had an old
      transmural myocardial infarction with abnormal Q waves. In group A, the QRS axis
      had significantly shifted to the left in patients with left anterior descending
      artery (LAD) occlusion (from 68.0 +/- 42.7 degrees to 40.2 +/- 44.6 degrees, P <
      0.001); however in those patients without involvement of the major septal branch,
      significant axis changes were not observed (from 53.6 +/- 34.1 degrees to 49.8 +/
      33.1 degrees). When the right coronary artery (RCA) was occluded in group A, the
      QRS axis shifted to the right significantly (from 63.2 +/- 40.0 degrees to 89.8
      +/- 30.1 degrees. P < 0.01); during left circumflex artery (LCX) occlusion, no
      significant axis shift was observed. In group B, no significant axis shift was
      observed either in patients with occlusion of the LAD or the RCA. It is concluded
      that transient left axis deviation reflects an obstructive lesion of the proximal
      portion of the LAD with involvement of the major septal branch, and transient
      right axis deviation reflects an obstructive lesion of the RCA.

PMID- 7821319
TI  - A clinical study of amiodarone as a single oral dose in patients with recent
      onset atrial tachyarrhythmia.
AB  - Forty-five patients with recent-onset sustained atrial tachyarrhythmia (mean
      heart rate at entry; 140.0 +/- 3.5 beats.min-1) associated with various
      cardiovascular diseases were treated by oral amiodarone, given as a single
      loading dose of 25.7 +/- 0.9 mg.kg-1 body weight. Conversion to sinus rhythm was
      observed in 29 patients during the first 24 h of treatment, leading to a success
      rate of 64.4%. Five additional patients converted to sinus rhythm with
      continuation of oral amiodarone, (10-15 mg.kg-1 by day) with a mean delay of 4.2
      days. A similar population of 27 patients (mean heart rate at entry; 140 +/- 3
      beats.min-1) was treated by intravenous amiodarone, given as a bolus infusion of
      3-5 mg.kg-1 over 30 min (mean; 4.1 +/- 0.2 mg.kg-1), followed by a continuous
      infusion of 10-15 mg.kg-1 for 24 h (mean; 11.1 +/- 0.7 mg.kg-1). Eighteen
      patients converted to sinus rhythm during the first 24 h of therapy, leading to a
      success rate of 66.7%. Minor adverse effects of therapy were observed in two
      patients given oral amiodarone, and in seven given intravenous amiodarone. No
      major effect was observed. We suggest that amiodarone given as a single oral
      loading dose of 25-30 mg.kg-1 body weight is an effective, simple and well
      tolerated therapy, suitable for most patients with recent-onset ATA.

PMID- 7821320
TI  - Atrial flutter can be terminated by a class III antiarrhythmic drug but not by a
      class IC drug.
AB  - In atrial flutter, chemical conversion with class I drugs is often unsuccessful,
      whereas class III drugs seem more promising. The different electrophysiological
      effects of these drugs may explain this discrepancy. To date, only experimental
      data show the differential effects of these drugs on conversion rate and atrial
      flutter cycle length. This study evaluates the effects of the class IC
      antiarrhythmic drug flecainide, and of dofetilide, a new class III drug, on
      conversion rate and flutter cycle length in patients with atrial flutter.
      Flecainide (11 patients) was given as an intravenous bolus of 2 mg.kg-1 in 10 min
      and dofetilide (10 patients) as a maximum intravenous bolus of 8 micrograms.kg-1
      in 15 min. Baseline characteristics were comparable between both groups. Only one
      patient treated with flecainide converted to sinus rhythm. This patient showed
      the largest flutter cycle length increase (280 to 420 ms). By contrast, seven of
      the 10 patients treated with dofetilide converted to sinus rhythm. Patients
      treated with flecainide showed a significantly larger increase in atrial flutter
      cycle length at the end of the infusion compared to the dofetilide-treated
      patients (from 226 +/- 28 to 317 +/- 52 ms vs from 221 +/- 26 to 239 +/- 39 ms,
      respectively). In conclusion, dofetilide is more effective than flecainide in the
      conversion of atrial flutter to sinus rhythm, despite the fact that flecainide
      produced a more prolonged flutter cycle length. Thus, action potential
      prolongation in the absence of conduction slowing seems more effective in
      terminating human atrial flutter than depression of the excitability.

PMID- 7821321
TI  - Prolongation of monophasic action potential duration and the refractory period in
      the human heart by tedisamil, a new potassium-blocking agent.
AB  - The effect of intravenous tedisamil (0.3 mg.kg-1), a newly developed potassium
      blocking agent, on ventricular repolarization was studied in 10 patients (three
      women, seven men; mean age 53 +/- 8 years) with coronary artery disease (stenoses
      < or = 60%). Left ventricular monophasic action potentials, effective refractory
      periods and surface electrocardiograms were recorded during sinus rhythm and
      during constant atrial pacing at cycle lengths of 600, 500 and 400 ms. Under
      tedisamil there was a 12% reduction of heart rate and in parallel a prolongation
      of QTc interval (+10%) and left ventricular monophasic action potential duration
      (+16% at 90% repolarization). QRS duration remained unchanged. Tedisamil
      increased the duration of monophasic action potentials during constant atrial
      pacing, indicating a direct prolongation effect on left ventricular
      repolarization independent of sinus node activity. By increasing the atrial
      pacing rate this prolonging effect diminished. Left ventricular effective
      refractory periods also increased in a frequency-dependent fashion with a greater
      prolongation effect at long cycle lengths as compared to short cycle lengths. The
      ratio between effective refractory period and monophasic action potential
      duration, however, remained constant, independent of heart rate. We conclude that
      tedisamil is bradycardiac at the dose tested and has a reverse use dependent
      prolongation effect on left ventricular repolarization and refractoriness. The
      electrophysiologic profile is consistent with a class III antiarrhythmic
      classification.

PMID- 7821322
TI  - Radiofrequency catheter ablation of accessory pathways associated with a coronary
      sinus diverticulum.
AB  - In two patients with a symptomatic posteroseptally localized accessory
      atrioventricular pathway, but with distinct electrocardiographic patterns, a
      coronary sinus diverticulum appeared to be the site of this connection.
      Radiofrequency catheter ablation in the diverticulum was implemented to interrupt
      the pathway in both cases. This study demonstrates the necessity to perform
      coronary sinus angiography when ablation attempts in the posteroseptal region are
      not immediately successful, or optimal signals are not detected.

PMID- 7821323
TI  - Chronic irregular idiopathic ventricular tachycardia with myocardial dysfunction
      suppressed by verapamil in an adult.
AB  - We report a case of an almost permanent ventricular tachycardia that occurred in
      a 39-year-old man a few weeks before admission to the hospital. This arrhythmia
      was noticeable by its total irregularity and its association with a left
      ventricular dysfunction. The precise nosological frame for the arrhythmia was
      difficult to define. This case presented as an idiopathic left ventricular
      tachycardia, the features of which could be consistent with an atypical
      parasystole. The rapid abolition of the rhythm disturbance by oral verapamil
      without recurrence at 6 months resulted in normalization of the contractile
      function.

PMID- 7821324
TI  - Non-Hodgkin's lymphoma related eosinophilic endomyocardial disease.
AB  - Two patients with eosinophilic endomyocardial disease related to peripheral T
      cell lymphomas are reported. Both patients were free of cardiac symptoms at
      presentation and during follow-up. Routine two dimensional echocardiography
      revealed bi-apical ventricular obliteration, which was also seen on MR imaging.
      On the T1-weighted sequence, the thickened endocardium appeared with an
      isointense signal. Gadolinium DOTA provided an enhanced contrast of the internal
      part of the left ventricular wall. On T2-weighted sequence, a thin hypointense
      curvilinear structure drew a dividing line between the internal, endocardial, and
      the external, myocardial area. Left-ventricular systolic and diastolic functions
      remained unaltered during subsequent follow-up.

PMID- 7821325
TI  - Accelerated coronary artery disease in a young woman with pseudoxanthoma
      elasticum and elevated lipoprotein(a).
AB  - Pseudoxanthoma elasticum frequently has cardiovascular involvement. We describe a
      29-year-old woman with pseudoxanthoma elasticum and accelerated coronary artery
      disease who was found to have a highly elevated lipoprotein(a). This unique
      combination is, most likely, responsible for the clinical presentation of our
      case.

PMID- 7821326
TI  - Importance of maintained atrio-ventricular synchrony in patients with pacemakers.
AB  - The effect of atrial contraction on cardiac function is reviewed in patients with
      dual chamber and rate-responsive ventricular pacemakers. The question posed was
      is there any haemodynamic, clinical or prognostic advantage of AV synchrony in
      dual chamber pacemakers in comparison to rate-responsive ventricular pacemakers?
      Optimal AV delay in dual chamber pacing favours cardiac performance at rest,
      while during exercise the increase in heart rate rather than AV synchrony
      influences cardiac performance and working capacity. However, there is little
      information on the benefit of maintained AV synchrony in patients' daily
      activities. Patients with pacemakers which maintain AV synchrony seem to have
      less morbidity and mortality than patients with ventricular stimulation alone,
      and there are comparable rates of complication in carriers of single and dual
      chamber pacemakers, the former showing problems with the pacemaker syndrome and
      the latter with atrial sensing and pacemaker-induced tachycardias. The
      disadvantage of dual chamber pacemakers are higher costs and time-consuming
      controls.

PMID- 7821327
TI  - Direct aortic distensibility measurements and their reproducibility.

PMID- 7821328
TI  - A bunch of grapes revisited.

PMID- 7821329
TI  - Plasminogen mediates an interaction between microglia and dopaminergic neurons.
AB  - Plasminogen (PGn), which was identified as a secretory product from microglia,
      increased dopamine uptake and the number of tyrosine-hydroxylase-expressing
      neurons in cultured rat mesencephalic neurons. 125I-PGn was found to bind
      specifically much more to mesencephalic neurons compared to other glial cells.
      The binding was also recognized in plasma membrane prepared from embryonic rat
      brain. Furthermore, ligand blotting analysis revealed that 125I-PGn binds to a 45
      kD protein in plasma membrane. These results suggest that PGn-dependent
      neurotrophic effects may be induced through the specific binding of PGn to the 45
      kD PGn-receptor-like protein in neurons.

PMID- 7821330
TI  - Dilemma in the treatment of Parkinson's disease with L-dopa.
AB  - L-Dopa pioneered the symptomatic therapy of Parkinson's disease. While this
      treatment proved effective in the treatment of parkinsonian akinesia, rigidity
      and tremor, prolonged L-dopa treatment was often noted to result in dyskinesia,
      psychosis and 'on-off' phenomena. This increasing disability of L-Dopa-treated
      parkinsonian patients, however, is not correlated with the duration of L-dopa
      treatment. Mortality due to Parkinson's disease has decreased significantly after
      the introduction of L-dopa treatment. The development of D1-selective dopamine
      agonists and the introduction of neuroprotective rather than symptomatic therapy
      are required for treating Parkinson's disease.

PMID- 7821331
TI  - Neuron damage induced by some potent kainoids and neuroprotective action of new
      agonists for metabotropic glutamate receptors.
AB  - Selective and characteristic neuron damage induced by acromelic acid, a potent
      kainate analogue, was investigated in comparison to a kainate-induced one. A
      single systemic injection of acromelic acid A caused behavioral and pathological
      effects distinct from those seen after systemic kainate. There was an initial
      marked tonic extension of the rat hindlimb, often followed by convulsions and, in
      surviving rats, by a transient flaccid paralysis and ultimately, a persistent
      spastic paraplegia. Pathological examination suggested specific lesions of
      interneurons in the lower spinal cord with little or no damage to the hippocampal
      neurons preferentially affected by systemic kainate. Another agonist for kainate
      type receptors, which is not a kainoid, demonstrated neurological symptoms and
      neuron damage quite similar to those of kainate. Pharmacological actions of our
      newly developed agonists for metabotropic glutamate receptors were described with
      special reference to kainate excitotoxicity. Intraventricular DCG-IV, a new
      agonist, caused selective neuron damage in the cingulate cortex and the
      hippocampal subiculum at relatively high doses, but other agonists did not cause
      neuron damage in the rat. DCG-IV considerably alleviated the kainate-induced
      limbic seizures. At relatively low doses, DCG-IV protected some kinds of neurons
      in the hippocampal CA3 and the amygdala against kainate neurotoxicity, when
      intraventricularly injected to the rat. These new agonists would provide useful
      probe for elucidating the mechanism underlying neuron damage induced by kainate
      type agonists.

PMID- 7821332
TI  - Levodopa and dopamine agonists in the treatment of Parkinson's disease:
      advantages and disadvantages.
AB  - Recent studies have suggested that free radicals play a key role in the
      progression of Parkinson's disease (PD). Although levodopa is the most effective
      therapeutic agent in the treatment of PD and has improved the quality of life and
      increased life expectancy, its beneficial effects are not permanent. Long-term
      treatment with levodopa produces a variety of side effects in patients with PD.
      We have previously reported that levodopa may accelerate the progression of PD in
      certain patients. To determine whether neuronal damage can be caused by levodopa
      overdoses, we estimated the effects of levodopa on free radical formation.
      Electron spin resonance spectrometry showed that levodopa oxidation produced
      levodopa radicals. Furthermore, chronic administration of levodopa increased
      thiobarbituric acid-reacting substances (TBARS) in various brain regions of 6
      hydroxydopamine (6-OHDA; i.c.v.)-pretreated mice, although levodopa
      administration in control mice had no effect on TBARS. These results indicate
      that high dose levodopa accelerates neuronal degeneration in some parkinsonian
      brains. We then evaluated the protective effects of bromocriptine on striatal
      dopaminergic neurons, with determination of dopamine (DA) and its metabolites as
      markers. Pretreatment of bromocriptine completely protected mice against the
      decreases in striatal DA and its metabolites induced by intracerebroventricular
      injection of 6-OHDA, while levodopa/carbidopa had no protective effects.
      Furthermore, in an in vitro system that generated .OH from FeSO4-H2O2,
      bromocriptine dose-dependently scavenged .OH. These findings clearly indicate
      that bromocriptine has neuroprotective effects against neurotoxins such as 6
      OHDA, probably due in part to its free redical scavenging activity.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7821333
TI  - Seven-year follow-up study of bromocriptine therapy for Parkinson's disease.
AB  - A 7-year nationwide study of bromocriptine monotherapy and combination therapy
      with bromocriptine and levodopa in Parkinson's disease is reported. Of 22
      patients who had been on bromocriptine monotherapy for 7 years (group B), 16
      remained improved or remained in the same stages of Hoehn and Yahr, and no
      wearing-off phenomenon or dyskinesia was observed. In another 56 patients who
      were started on bromocriptine alone, but in whom combination therapy with
      levodopa was instituted at some time in the 7 years (group BL), disease
      progressed faster than in group B. A wearing-off phenomenon and dyskinesia
      occurred in 34% and 5.4% of the patients, respectively. These manifestations
      appeared only after initiation of levodopa. The favorable course of group B
      suggests possible neuroprotective effects of bromocriptine or may be due to the
      inevitable selection of patients who had a favorable course originally.

PMID- 7821334
TI  - Short review on monoamine oxidase and its inhibitors.
AB  - Since monoamine oxidase is an enzyme catalyzing bioactive monoamines, inhibitors
      of monoamines are expected to prolong the activity of monoamines in tissue.
      Monoamine oxidase type B is an active form in brain, and its preferential
      substrate is dopamine that is the most constantly reduced monoamine in
      Parkinson's disease brain. Therefore, it is natural to expect that monoamine
      oxidase inhibitors, deprenyl or lazabemide, could exhibit beneficial effects on
      parkinsonism, i.e. symptomatic effects. This short review summarizes
      characteristics of monoamine oxidase from biochemical and pharmacological points,
      and then briefly mentions the situation of clinical evaluation studies of
      deprenyl and lazabemide in terms of antiparkinsonian effects in Japan.

PMID- 7821335
TI  - Anti-inflammatories and gastroduodenal damage: therapeutic options.
AB  - The association between use of nonsteroidal anti-inflammatory drugs (NSAIDs) and
      the development of upper gastrointestinal (GI) damage is well established.
      Studies have indicated that 12-30% of NSAID users will develop gastric ulcers and
      that 2-19% will develop duodenal ulcers. Furthermore, many NSAID-induced ulcers
      are "silent" and are only discovered when complications occur. When possible, the
      most effective method of preventing NSAID-induced gastropathy is discontinuation
      of NSAIDs or a reduction in the NSAID dosage. For patients who require continued
      NSAID therapy, four classes of drugs have been evaluated for their potential
      protective effects against NSAID-induced gastroduodenal damage:H2-receptor
      antagonists (eg, ranitidine), proton pump inhibitors (eg, omeprazole), acid
      barrier compounds (eg, sucralfate), and prostaglandin E1 analogues (eg,
      misoprostol). H2-receptor antagonists have not been shown to be effective in
      preventing NSAID-induced gastric ulcers, and sucralfate has not been shown to be
      effective in preventing NSAID-induced gastric or duodenal ulcers. Similarly,
      newer proton pump inhibitors, such as omeprazole, do not appear to protect the
      stomach against NSAID-induced damage. In contrast, misoprostol has proven its
      efficacy in preventing both gastric and duodenal ulcers in arthritis patients
      taking NSAID therapy.

PMID- 7821336
TI  - Arthrotec: a therapeutic option in the management of arthritis.
AB  - Arthrotec (Searle) is a new concept in NSAID therapy that provides powerful anti
      inflammatory efficacy with enhanced upper GI safety. Arthrotec comprises an
      enteric-coated core of diclofenac sodium (50 mg) surrounded by a mantle of
      misoprostol (200 mcg). Two multicentre trials evaluated the efficacy of Arthrotec
      in rheumatoid arthritis (RA) and osteoarthritis (OA) patients who were randomised
      to receive either Arthrotec or diclofenac. The results of all arthritis
      assessments showed Arthrotec to be as effective as diclofenac in treating the
      signs and symptoms of RA and OA. Two endoscopic studies compared the
      antiarthritic efficacy and gastroduodenal safety of Arthrotec and diclofenac. In
      a 12-week study of RA patients, the antiarthritic efficacy of Arthrotec was
      equivalent to diclofenac; in addition, 60% fewer patients taking Arthrotec
      experienced ulcers than did those taking diclofenac (4.4% Arthrotec vs 11.1%
      diclofenac: P = 0.034). In a 4-week study of OA patients, Arthrotec's efficacy
      was equivalent to that of diclofenac and the Arthrotec group developed no ulcers,
      while 3.6% of the diclofenac group had ulcers (P = 0.015). In a trial conducted
      to compare the efficacy and upper gastroduodenal safety of Arthrotec with those
      of piroxicam and naproxen, patients with OA received either Arthrotec BID
      piroxicam 10 mg BID, or naproxen 375 BID for 4 weeks. Arthritis assessments
      showed Arthrotec to be at least as effective as piroxicam and naproxen in
      treating OA. Post-treatment endoscopy data indicated that gastroduodenal ulcers
      developed in 1.5% of patients receiving Arthrotec, 10.3% of patients receiving
      piroxicam, and 8.6% patients in the naproxen group.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7821337
TI  - The economic consequences of NSAID-induced gastrointestinal damage.
AB  - The secondary gastrointestinal effects associated with the use of nonsteroidal
      anti-inflammatory drugs (NSAIDs) are well documented in the medical literature.
      The "iatrogenic" cost arising from the treatment of these secondary effects,
      however, is less well known. Existing epidemiologic and clinical studies report
      that the cost of NSAIDs is multiplied by a coefficient that ranges from 1.36 to 3
      when the cost of treating the induced gastroduodenal damage is taken into
      account. A simple methodology has been developed to calculate the "shadow price"
      of an NSAID by incorporating the costs of treating the gastroduodenal damage,
      thus yielding a figure that reflects the real economic burden of NSAID therapy.
      Using study data from seven countries, the cost effectiveness of prophylactic
      treatment with misoprostol--a prostaglandin analogue whose efficacy has been
      proven in the prevention of gastroduodenal ulcers in arthritic patients treated
      with NSAIDs--is reviewed. In the majority of cases, the financial benefits of
      preventing the ulcers equal or surpass the cost of prevention.

PMID- 7821338
TI  - Historical overview of NSAIDs.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) have become valuable therapeutic
      agents in the treatment of arthritic conditions. In 1971, Vane demonstrated that
      the primary mechanism of action of aspirin and related drugs was inhibition of
      synthesis of prostaglandins from arachidonic acid. Although Vane's prostaglandin
      hypothesis has been generally accepted, various studies have suggested that
      additional mechanisms may have a role in the effects of NSAIDs. With the
      increasing number of NSAIDs available and with recent information on the side
      effects associated with NSAID therapy, it becomes important to examine whether
      these drugs are being used in the most appropriate manner.

PMID- 7821339
TI  - Anti-inflammatory drugs and their effects on cartilage synthesis and renal
      function.
AB  - Growing evidence suggests that nonsteroidal anti-inflammatory drugs (NSAIDs),
      while able to alleviate inflammation, may damage articular cartilage, though both
      chondrodestructive and chondroprotective activities have been observed with
      different NSAIDs. Experiments conducted on explants of normal and osteoarthritic
      human cartilage have shown that certain NSAIDs at pharmacologic concentrations
      achievable in man consistently inhibit glycosaminoglycan (GAG) synthesis. The
      addition of the prostaglandin E1 analogue misoprostol consistently reversed these
      inhibitory effects in a dose-related manner. Paradoxically, with some NSAIDs,
      such as diclofenac and aspirin, misoprostol was also able to enhance GAG
      synthesis above control levels, especially in osteoarthritic cartilage. This
      supports findings from other work that NSAIDs exert effects other than through
      inhibition of cyclooxygenase, direct action on cell membranes being one of these
      alternative mechanisms of action. Additionally it is interesting to note and may
      be of clinical relevance that misoprostol on its own also stimulates GAG
      synthesis in explants of human osteoarthritic cartilage whilst exerting no
      apparent effect on healthy cartilage with a normal GAG turnover. With regard to
      renal aspects, the effects of NSAIDs are readily explicable in terms of
      interference with prostanoid synthesis. The consequent inhibition exerted on
      vasodilatory prostaglandins (PGs), which oppose vasoconstrictor action induced by
      substances such as thromboxane or leukotrienes, upsets the balance that maintains
      renal function. In situations in which there is reduced renal reserve, reduction
      of renal PG synthesis by NSAIDs will adversely affect maintenance of renal blood
      flow and glomerular filtration rate and excretion of sodium, potassium, and
      water. Patients with alcoholic cirrhosis manifest this type of compromised renal
      function and in them misoprostol reverses the adverse effects of indomethacin on
      renal hemodynamics and partially reverses indomethacin-induced renal sodium
      retention. Although the clinical significance of these data is not yet
      established, exogenous administration of specific PGs may be able to minimize the
      deleterious actions of NSAIDs.

PMID- 7821340
TI  - Antidepressant activity of non-competitive and competitive NMDA receptor
      antagonists in a chronic mild stress model of depression.
AB  - The antidepressant properties of the non-competitive NMDA receptor antagonist, MK
      801 (dizocilpine), and the competitive NMDA receptor antagonist, CGP 37849 (DL
      (E)-2-amino-4-methyl-5-phosphono-3-pentonoic acid) and its (R)-enantiomer CGP
      40116, were studied in a chronic mild stress model of depression. In this model,
      animals subjected to a variety of mild stressors for a prolonged period of time
      show a substantial decrease in the consumption of palatable sucrose solution
      (anhedonia). It was previously demonstrated that the chronic mild stress-induced
      anhedonia can be reversed by chronic treatment with various antidepressant drugs.
      In this study we found that the stress-induced deficit in sucrose intake was
      gradually reversed by chronic (4-5 weeks) treatment with MK-801 (0.3 mg/kg i.p.),
      CGP 37849 (5 mg/kg i.p.) and CGP (25 mg/kg p.o.). The magnitude of this effect
      and its time course were comparable to those observed following similar
      administration of imipramine (10 mg/kg i.p. or p.o.). The increase in sucrose
      intake following chronic administration of imipramine and NMDA receptor
      antagonists was specific to stressed animals; the behaviour of non-stressed
      controls was unchanged by any of the drugs tested. These results confirm those of
      previous studies, carried out on 'normal' animals, suggesting that antagonists of
      NMDA receptors may have antidepressant properties.

PMID- 7821341
TI  - Effects of two chemically related new Ca2+ channel antagonists, SR33557
      (fantofarone) and SR33805, on the L-type cardiac channel.
AB  - Fantofarone (SR33557) is a substituted indolizine and SR33805 is a substituted
      indole. These drugs have been shown to specifically bind to the alpha 1 subunit
      of the L-type Ca2+ channel at the same site, distinct from those of the classical
      1,4-dihydropyridine, phenylalkylamine or benzothiazepine Ca2+ antagonists, but in
      negative allosteric interaction with them. The present work shows that
      fantofarone and SR33805 block L-type but not T-type Ca2+ channels in mouse
      cardiac cells in primary culture. This block is voltage-dependent. Fantofarone
      and SR33805 are potent Ca2+ channel blockers in depolarized conditions (i.e. at a
      holding potential of -40 mV) with an EC50 = 1.4 and 4.1 nM, respectively. In
      polarized conditions (i.e. at a holding potential of -80 mV), SR33805 is a better
      Ca2+ channel blocker (EC50 = 33 nM) than fantofarone (EC50 = 0.15 microM).
      Therefore differences in their chemical structures make the blocking action of
      fantofarone more sensitive to voltage than that of SR33805.

PMID- 7821342
TI  - The effect of acetylcholine and related drugs on currents at the frog motor nerve
      terminal.
AB  - Acetylcholine, acetylthiocholine, carbachol, suberyldicholine, propionylcholine,
      succinylcholine, methylfurmethide and F 2268 were tested on motor nerve ending
      currents recorded with an extracellular microelectrode. The isolated and
      transversally cut cutaneous pectoris muscle of frog Rana ridibunda was used. Only
      acetylcholine and acetylthiocholine affected the spike waveforms in a
      concentration-dependent manner. Lower concentrations (1-6 x 10(-4) M) prolonged
      the inward Na+ current and increased the outward K+ current at the proximal and
      central parts of the nerve terminal. Most remote parts of the terminal were not
      affected. At 7 x 10(-4) M and higher, both drugs further prolonged the Na+
      current and eliminated the K+ component of the spike. The potentiating effect of
      acetylcholine and acetylthiocholine on the K+ phase of nerve terminal current
      disappeared after treatment with tetraethylammonium and 4-aminopyridine. The
      effect also disappeared when synaptic cholinesterase was inhibited by the
      anticholinesterases or by treatment with collagenase. Reactivation of
      cholinesterase by dipyroxime restored the facilitating effect of acetylcholine.
      Choline and slight acidification to pH 6.8 did not mimic the acetylcholine action
      on the terminal currents. Facilitation of the K+ current by acetylcholine was not
      calcium-dependent. The results indicate that lower acetylcholine concentrations
      inhibit the delayed rectifier only, whereas 7 x 10(-4) M and higher
      concentrations of acetylcholine depress all outward currents of the terminal.

PMID- 7821344
TI  - Influence of N omega-nitro-L-arginine methyl ester, LY83583, glybenclamide and
      L158809 on pulmonary circulation.
AB  - The effects of N omega-nitro-L-arginine methyl ester, an inhibitor of nitric
      oxide synthase; 6-anilino-5,8-quinolinedione (LY83583), an inhibitor of soluble
      guanylate cyclase; glybenclamide, a ATP-sensitive K+ channel blocking agent; and
      5,7-dimethyl-2-ethyl-3-[[2'-(1H-tetrazol-5-yl)-[1,1']-biphenyl-4- yl]methyl]-3H
      imidazo[4,5-b]pyridine (L158809), an angiotensin II type I receptor antagonist,
      on the response to ventilatory hypoxia were investigated in the isolated blood
      perfused rat lung. Under conditions of controlled pulmonary blood flow, and
      constant left atrial pressure, injections of glybenclamide into the pulmonary
      arterial perfusion circuit significantly increased baseline pulmonary arterial
      perfusion pressure, whereas administration of N omega-nitro-L-arginine methyl
      ester produced smaller increases in baseline tone. Ventilatory hypoxia (3% O2-5%
      CO2-92% N2) significantly increased pulmonary arterial perfusion pressure and the
      response was reproducible with respect to time. Following administration of N
      omega-nitro-L-arginine methyl ester or LY83583, the response to hypoxia was
      significantly increased, whereas the response to hypoxia was not changed by
      glybenclamide or atropine. N omega-Nitro-L-arginine methyl ester also
      significantly enhanced pressor responses to angiotensin II, but had no effect on
      the pressor response to serotonin. When pulmonary vascular tone was increased
      with hypoxia, vasodilator responses to acetylcholine were inhibited by N omega
      nitro-L-arginine methyl ester and vasodilator responses to levcromakalim were
      reduced by glybenclamide. In addition, L158809 did not alter the pressor response
      to hypoxia, whereas responses to angiotensin II were reduced in a selective
      manner.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7821343
TI  - Neuroendocrine responses produced by enantiomeric pairs of drugs that interact
      with phencyclidine and sigma receptors.
AB  - The present study characterized the response of the hypothalamo-pituitary-adrenal
      axis after the acute administration of enantiomeric pairs of drugs that bind to
      phencyclidine (PCP) and sigma receptors. Rats were injected with the enantiomers
      of 1-(1-phenylcyclohexyl)-3-methylpiperidine (PCMP), N-allylnormetazocine (SKF
      10,047), dioxadrol (dexoxadrol and levoxadrol) or pentazocine, and plasma levels
      of adrenocorticotropin (ACTH) and corticosterone were determined by
      radioimmunoassay. The effects of the enantiomers of PCMP and dioxadrol showed
      stereospecificity as both (+)-PCMP and dexoxadrol increased plasma levels of ACTH
      and corticosterone but (-)-PCMP and levoxadrol had no effect. Whereas (-)
      pentazocine produced greater responses than (+)-pentazocine, the two enantiomers
      of SKF 10,047 did not show stereoselectivity. Although the potency of the
      enantiomers of PCMP and dioxadrol parallel their affinity for binding to PCP
      receptors, the potency of the enantiomers of pentazocine did not. These results
      suggest that although the stimulation of the hypothalamo-pituitary-adrenal axis
      by PCP and drugs with PCP-like activity might be due to interactions with PCP
      receptors, the effects of pentazocine also involve interactions at other sites.

PMID- 7821345
TI  - Benzodiazepine receptor ligands modulate ethanol drinking in alcohol-preferring
      rats.
AB  - The effects of benzodiazepine receptor ligands with different intrinsic activity
      profiles were studied on voluntary ethanol consumption in the selectively bred
      alcohol-preferring AA (Alko, Alcohol) rat line, and compared to those of an
      opiate antagonist, naloxone, and a serotonin uptake inhibitor, citalopram. The
      rats were first allowed to develop a strong preference for 10% (v/v) ethanol
      solution in tap water over plain water until their ethanol consumption
      stabilized. Thereafter, the period when ethanol solution was available for the
      rats was gradually reduced to 4 h, 3 times a week, every second working day. The
      acute effects of positive allosteric modulators (agonists) of the gamma
      aminobutyric acid type A (GABAA)/benzodiazepine receptor [midazolam, abecarnil,
      ethyl 5-benzyloxy-4-methoxymethyl-beta-carboline-3-carboxylate (ZK 91296),
      bretazenil, and 2,5-dihydro-2-(4-methylphenyl)-3H-pyrazolo[4,3-C]quinolin-3(5H)
      on e (CGS 9895)] and of negative allosteric modulators [inverse agonists, ethyl 8
      azido-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5- a][1,4]benzodiazepine-3
      carboxylate (Ro 15-4513) and t-butyl 5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5
      a]thieno[2,3- f][1,4]diazepine-3-carboxylate (Ro 19-4603)] were tested after i.p.
      injections of three different drug doses using saline injections as a control
      treatment. The benzodiazepine agonists had rather modest effects on ethanol
      intake, measured 1 and 4 h after the injections, whereas the inverse agonists and
      naloxone strongly decreased ethanol consumption. Acute citalopram had no clear
      effect on ethanol drinking, but it slightly decreased the consumption of novel
      food during the 4-h session, as did all other benzodiazepine agonists except
      bretazenil. Neither the inverse agonists nor naloxone had any significant effect
      on food intake.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7821346
TI  - Glucocorticoid and mineralocorticoid receptors differentially modulate cultured
      dopaminergic neurons of rat ventral mesencephalon.
AB  - Activation of kappa-opioid receptors by U69,593 in a concentration of 1 microM
      maximally inhibited dopamine release. Withdrawal from chronic (4 days) treatment
      with U69,593 (1 microM) induced a long-lasting (at least 7 days) increase (30
      50%) in [3H]dopamine release induced by 25 mM K+ from cultured rat mesencephalic
      neurons without causing functional kappa-opioid receptor desensitization.
      Incubation of these cultured neurons with the glucocorticoid agonist,
      dexamethasone (3 nM), had no effect on basal or 25 mM K(+)-induced dopamine
      release, whereas the steroid completely blocked the development of opiate-induced
      neuronal supersensitivity to depolarization. This blockade was found to be
      concentration-dependent, with an EC50 of about 0.3 nM and was not associated with
      changes in corticotropin-releasing factor (CRF) receptor, dopamine D2
      autoreceptor or kappa-opioid receptor functioning. Therefore, opioid and
      glucocorticoid receptors appear to be co-localized in dopaminergic neurons of rat
      ventral mesencephalon and interact in a functionally antagonistic manner.
      Interestingly, the mineralocorticoid agonist, aldosterone (5 nM), itself
      increased K(+)-stimulated [3H]dopamine release by about 25%, consistent with the
      putative role of mineralocorticoid receptors in maintaining neuronal
      excitability. Moreover, whereas 1 nM corticosterone appeared to mimic the
      dopamine release-facilitating effect of aldosterone, 30 nM corticosterone
      displayed a modulatory effect similar to that of dexamethasone. Thus, whereas
      mineralocorticoid receptors that are already activated at low plasma
      corticosterone levels may uphold neuronal sensitivity to depolarizing stimuli,
      activation of glucocorticoid receptors by higher plasma corticosterone levels may
      prevent the development of neuronal supersensitivity, e.g. following chronic
      activation of kappa-opioid receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7821347
TI  - Impaired oxidation of pyruvate in human embryonic fibroblasts after exposure to L
      dopa.
AB  - The effect of 3,4-dihydroxyphenylalanine (L-dopa) treatment on the ability of
      intact human cells to metabolize substrates for mitochondrial oxidative
      phosphorylation was studied in embryonic fibroblasts. Treatment with L-dopa (100
      400 microM) for 48 h significantly reduced the oxidation of pyruvate but had no
      effect on succinate oxidation. The effect was dose-dependent and was still
      present 2 days after removal of L-dopa. Ascorbic acid (200 microM) protected the
      cells from the effects of L-dopa; ascorbate alone enhanced pyruvate but not
      succinate oxidation.

PMID- 7821348
TI  - Quantitative autoradiography of 4'-ethynyl-4-n-[2,3
      3H2]propylbicycloorthobenzoate binding to the GABAA receptor complex.
AB  - 4'-Ethynyl-4-n-[2,3-3H2]propylbicycloorthobenzoate ([3H]EBOB) binding to the
      GABAA receptor complex was characterized autoradiographically in rat brain and
      then its binding in human brain was investigated. [3H]EBOB binding was saturable,
      specific and identified a single population of binding sites. The Kd obtained
      from saturation studies was 4.59 nM. Picrotoxin produced dose-dependent
      inhibition of [3H]EBOB binding and saturation analysis indicated a competitive
      interaction. Isoguvacine inhibited [3H]EBOB binding with regionally different
      effects. Bicuculline increased [3H]EBOB binding only in the cerebellar granule
      cell layer. In human cerebellum, a high level of [3H]EBOB binding sites was seen
      in the granule cell layer. These results suggest that [3H]EBOB binds to the
      picrotoxin binding site associated with the GABAA receptor complex, that regional
      differences in GABAA agonist and antagonist modulation of [3H]EBOB binding
      reflect underlying regional differences in GABAA receptor subunit composition,
      and that there is a species difference in GABAA receptor distribution between
      human and rat cerebellum.

PMID- 7821349
TI  - Effects of two K+ channel openers, aprikalim and pinacidil, on hypoxic pulmonary
      vasoconstriction.
AB  - This study investigated the effects of two K+ channel openers, aprikalim and
      pinacidil, on hypoxic pulmonary vasoconstriction induced in isolated rat lung
      perfused at constant flow. In order to evaluate the mechanism of the hypoxic
      vasoconstriction we also studied the effects of an inhibitor of the endothelium
      derived relaxing factor (EDRF), NG-nitro-L-arginine methyl ester (100 microM), an
      inhibitor of the guanylate cyclase, methylene blue (30 microM), two K+ channel
      blockers, glibenclamide (1 microM) and tetraethylammonium (20 mM). In normoxia,
      NG-nitro-L-arginine methyl ester, methylene blue, glibenclamide or
      tetraethylammonium did not enhance significantly the baseline perfusion pressure,
      suggesting that neither EDRF nor K+ channels are involved in the modulation of
      the low basal pulmonary vascular tone. In hypoxia, aprikalim and pinacidil (0.03
      3 microM) induced a concentration-dependent decrease of pulmonary pressure,
      exhibiting their spasmolytic effects in acute hypoxia. The hypoxic pressure
      response was significantly increased by NG-nitro-L-arginine methyl ester,
      methylene blue and tetraethylammonium, but not by glibenclamide suggesting that
      EDRF and K+ channels other than ATP-sensitive K+ channels are involved in the
      modulation of the hypoxic pressure response. The spasmolytic effects of aprikalim
      and pinacidil (1 microM) were not modified by NG-nitro-L-arginine methyl ester,
      but were partially reduced by tetraethylammonium and completely abolished by
      glibenclamide, suggesting that these effects are mainly but not exclusively
      mediated through ATP-sensitive K+ channel opening.

PMID- 7821350
TI  - Effect of vitamin K2 (menatetrenone) on osteoclast-like cell formation in mouse
      bone marrow cultures.
AB  - The effects of menatetrenone, a vitamin K2 homologue, on osteoclast-like cell
      formation in mouse bone marrow culture were investigated. After 7 days of
      incubation, menatetrenone at 10(-6) M, 3 x 10(-6) M and 10(-5) M dose dependently
      inhibited the tartrate-resistant acid phosphatase-positive multinucleated cell
      formation induced by 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). The addition of
      menatetrenone for the last 3 days of the 7-day incubation period was required to
      inhibit formation of multinucleated cells in response to 1,25(OH)2D3. Moreover,
      the addition of 1,25(OH)2D3 for the last 3 days was essential for multinucleated
      cell formation, and this activity was markedly inhibited by the simultaneous
      addition of menatetrenone. The inhibitory effects of menatetrenone on
      multinucleated cell formation may contribute to its ameliorative action on bone
      loss in vivo, and may indicate a new mechanism of vitamin K2 activity in bone
      metabolism.

PMID- 7821351
TI  - Role of 5-HT1A receptors in the antinociceptive action of 8-hydroxy-2-(di-n-
      propylamino)tetralin in the rat.
AB  - The role of 5-HT1A receptors in the antinociceptive action of 8-hydroxy-2-(di-n
      propylamino)tetralin (8-OH-DPAT) was investigated by using the shock titration
      test in rats. A subcutaneous injection of 300 micrograms/kg 8-OH-DPAT
      significantly raised the threshold for flinching, jumping and vocalization
      whereas 100 micrograms/kg only inhibited the flinch response. l-Propranolol and
      (+)-[N-tert-butyl-3-4-(2-methoxyphenyl)piperazin-1-yl-2-phenyl propanamide
      dihydrochloride], (+)-WAY100135, two antagonists at 5-HT1A receptors at 10 mg/kg
      s.c. antagonized the effect of 300 micrograms/kg 8-OH-DPAT on all measures. The
      effect of 300 micrograms/kg 8-OH-DPAT on the three measures was unmodified in
      rats which had received 150 micrograms 5,7-dihydroxytryptamine
      intracerebroventricularly 10 days before testing. The results suggest that 8-OH
      DPAT inhibits nociceptive responses by stimulating postsynaptic 5-HT1A receptors.

PMID- 7821352
TI  - Investigation of the role of tachykinin NK1, NK2 receptors and CGRP receptors in
      neurogenic plasma protein extravasation in dura mater.
AB  - The aim of this study was to investigate the role of tachykinin NK1 and NK2
      receptors, and calcitonin gene-related peptide (CGRP) receptors in neurogenic
      plasma protein extravasation, induced by electrical stimulation of the trigeminal
      ganglion, in dura mater of anaesthetised rats and guinea-pigs. This response was
      significantly (P < 0.05) blocked in both species by the selective peptide
      tachykinin NK1 receptor antagonist, GR82334 ([D-Pro9[spiro-gamma
      lactam]Leu10,Trp11]physalaemin-(1-11)) (0.02-0.2 mg/kg i.v.) whilst the selective
      tachykinin NK2 receptor antagonist, (+/-)-SR 48968 ((S)-N-methyl-N-[4-(4
      acetylamino-4-phenylpiperidino)-2-(3,4- dichlorophenyl) butyl] benzamide) (1
      mg/kg i.v.) was without effect. The CGRP receptor antagonist, alpha-CGRP-(8-37)
      (0.1 mg/kg i.v.) significantly (P < 0.05) blocked this response in dura mater of
      guinea-pigs but not rats. These results suggest that substance P, acting via
      tachykinin NK1 rather than NK2 receptors, mediates neurogenic plasma protein
      extravasation in dura mater and that CGRP may have an involvement in this
      response in guinea-pigs.

PMID- 7821353
TI  - Stimulation by carbachol of mucus gel thickness in rat stomach involves nitric
      oxide.
AB  - Instillation of carbachol (150 micrograms/kg) into the gastric lumen in vivo
      increased the thickness of the mucus gel layer. Intravenous administration of the
      inhibitor of nitric oxide (NO) synthase, NG-nitro-L- arginine methyl ester (L
      NAME, 0.4-5 mg/kg) dose-dependently reduced the stimulation by carbachol, the
      half-maximal inhibitory dose being 0.57 mg/kg. This effect of L-NAME was
      abolished by administration of L-arginine but not by D-arginine (100 mg/kg i.v.).
      By contrast L-NAME (5 mg/kg) did not reduce the stimulatory effect of
      intraluminal 16,16-dimethyl prostaglandin E2 (50 micrograms/kg) on mucus gel
      thickness. These results implicate NO in the cholinergic activation of gastric
      mucus secretion.

PMID- 7821354
TI  - Morphine-induced straub tail response: mediated by central mu2-opioid receptor.
AB  - The opioid receptor mechanism involved in the morphine induced straub tail
      response was investigated in mice. Morphine (2.5, 5, 10 and 20 mg/kg s.c.)
      produced a dose dependent straub tail response and analgesia (hot plate test).
      Naloxone (5 mg/kg s.c.) and the mu-opioid receptor antagonist beta-funaltrexamine
      (10 micrograms i.c.v.) blocked both the straub tail response and analgesia while
      the mu 1-opioid receptor selective antagonist naloxonazine (35 mg/kg s.c.)
      blocked only analgesia and did not affect the straub tail response. Morphine (20
      micrograms) administered by the i.c.v. route also produced the straub tail
      response as well as analgesia. Pretreatment with naloxonazine (35 mg/kg s.c.)
      antagonised i.c.v. administered morphine induced analgesia while the straub tail
      response was not affected. The results indicate that the morphine induced straub
      analgesia while the straub tail response was not affected. The results indicate
      that the morphine induced straub tail response is mediated by central mu 2-opioid
      receptors.

PMID- 7821355
TI  - Attenuation of the discriminative stimulus properties of cocaine by delta-opioid
      receptor antagonists.
AB  - The effects of selective delta-opioid receptor antagonists on the discriminative
      stimulus properties of cocaine were examined in rats trained to discriminate
      between cocaine (10 mg/kg) and saline. Pretreatment with naltrindole (a non
      selective delta-opioid receptor antagonist) and naltriben (a selective delta 2
      opioid receptor antagonist), but not 7-benzylidenenaltrexone (a selective delta 1
      opioid receptor antagonist), significantly attenuated the discriminative stimulus
      properties of cocaine. Naltrindole and naltriben attenuated the discriminative
      stimulus properties of doses of cocaine lower than the training dose. Although
      the effects produced by the training dose were not changed, our finding may have
      some bearing on the relative importance of the role of delta-opioid (especially
      delta 2-opioid) receptors in the discriminative stimulus properties of cocaine.

PMID- 7821356
TI  - Differential effects of chronic antidepressant treatment on 5-HT1C receptor
      binding sites in Wistar rat brain.
AB  - The effects of chronic clomipramine, imipramine and clorgyline on 5-HT1C
      receptors were studied in discrete brain regions, in male Wistar rats, using
      [3H]mesulergine to label the receptor binding sites. Clorgyline treatment
      significantly reduced [3H]mesulergine binding (Bmax values) in both the
      hypothalamus and striatum compared to saline-treated animals. There were no
      differences in the maximum number of [3H]mesulergine binding sites following
      clorgyline in the hippocampus, frontal cortex or brainstem. Neither clomipramine
      or imipramine treatment resulted in any significant changes in 5-HT1C receptor
      number in the brain regions examined here. Furthermore, the Kd values (receptor
      affinity) for [3H]mesulergine binding were not significantly different comparing
      treatment groups to control animals. The significant changes in discrete brain
      regions following chlorgyline treatment suggest that 5-HT1C receptors may be
      involved in the clinical efficacy for the treatment of depression and other
      neuropsychiatric disorders.

PMID- 7821357
TI  - Differential antagonism by MK-801 against antinociception induced by opioid
      receptor agonists administered supraspinally in mice.
AB  - Various doses of MK-801 ((+/-)-5-methyl-10,11-dihydro-5H-dibenzo(a,d) cyclohepten
      5, 10-imine maleate), a non-competitive N-methyl-D-aspartic acid (NMDA) receptor
      antagonist (0.001-1 microgram) injected intracerebroventricularly (i.c.v.) alone
      did not show any antinociceptive effect. MK-801 (0.001-1 microgram i.c.v.) dose
      dependently attenuated the inhibition of the tail-flick and hot plate responses
      induced by i.c.v. administered morphine (1 microgram), [D-Pen2, D-Pen5]enkephalin
      (DPDPE; 10 micrograms), and U50,488H (trans-3,4-dichloro-N-methyl-N-[2-(1
      pyrrolidinyl)cyclohexyl]benzeoce tamide ) 60 micrograms). However, the inhibition
      of the tail-flick and hot plate responses induced by i.c.v. administered beta
      endorphin (1 microgram) was not changed by i.c.v. administered MK-801. Our
      results indicate that, at the supraspinal level, NMDA receptors are involved in
      the production of antinociception induced by supraspinally administered morphine,
      DPDPE, and U50,488H but not beta-endorphin.

PMID- 7821358
TI  - Adenosine modulation of primed human neutrophils.
AB  - Human neutrophils have been demonstrated to possess both adenosine A1 and A2
      receptors: activation of adenosine A2 receptors inhibits the respiratory burst,
      assayed as superoxide anion production (O-2) from cells stimulated by the
      bacterial peptide N-formylmethionyl-leucyl-phenylalanine (FMLP). Exposure of
      neutrophils to different combinations of stimuli results in synergistic or primed
      responses. These responses can be measured by challenging the cells either with a
      combination of FMLP and platelet activating factor (PAF), or with a combination
      of PAF and the neuropeptide substance P, which by itself does not induce O-2
      production. In order to evaluate the ability of adenosine receptor agonists to
      inhibit O-2 production by primed or synergistically stimulated neutrophils, a non
      selective adenosine receptor agonist, 2-chloroadenosine, was tested in comparison
      with reportedly selective ligands of adenosine A1 and A2 receptor types, N6
      cyclopentyladenosine (CPA) and 2-[4-(2-carboxyethyl)phenethylamino]-5'-N-ethyl
      carboxamido adenosine (CGS 21680). The order of activity CGS 21680 > 2
      chloroadenosine > CPA indicates that adenosine A2 receptors mediate the
      inhibition of the respiratory burst even when neutrophils are primed or
      synergistically activated. 8-Phenyltheophylline antagonized the effects of these
      adenosine receptor agonists in a competitive way.

PMID- 7821359
TI  - The stereospecific effects of isoflurane isomers in vivo.
AB  - The anesthetic potency of racemic isoflurane and the optically pure stereoisomers
      was examined in rats. The (+) isomer was 53% more potent than the (-) isomer
      (minimum alveolar concentration (MAC) = 1.06 +/- 0.07% vs. 1.62 +/- 0.02%, P <
      0.05). MAC for racemic isoflurane was 1.32 +/- 0.03%. Both stereoisomers and the
      racemic isoflurane produced similar depression of arterial pressure. However, the
      (+) isomer blunted the cardiovascular response to a painful stimulus to a greater
      extent than did an equi-MAC dose of the (-) isomer. These are the first data to
      describe pharmacological differences between stereoisomers of a volatile
      anesthetic administered in vivo by the conventional route (inhaled) and measuring
      the clinically relevant index of anesthesia, MAC. These data are consistent with
      a receptor-mediated anesthetic mechanism by volatile anesthetics.

PMID- 7821360
TI  - In vivo quantification of dopamine D2 receptor parameters in nonhuman primates
      with [123I]iodobenzofuran and single photon emission computerized tomography.
AB  - [123I]Iodobenzofuran ([123I]IBF) is a new single photon emission computed
      tomography (SPECT) tracer for visualization of the dopamine D2 receptors. A
      tracer constant infusion paradigm was developed to measure the binding potential,
      density (Bmax) and affinity (KD) of the dopamine D2 receptor in baboons. Three
      baboons underwent both a single bolus and a constant infusion study. For the
      single bolus experiment, the striatal binding potential (134 +/- 24 ml g-1, mean
      +/- S.D.) was derived by kinetic analysis. For the constant infusion experiments,
      the striatal binding potential (127 +/- 16 ml g-1) was derived by equilibrium
      analysis. The two sets of experiments thus provided consistent data. Low specific
      activity constant infusion experiments were performed to measure KD (0.08 nM) and
      Bmax (12.7 nM). In vitro experiments carried out at 37 degrees C with [125I]IBF
      on rat striatal homogenate membranes provided results in agreement with the SPECT
      data. These studies suggested the feasibility of quantitation of dopamine D2
      receptor parameters with [123I]IBF SPECT imaging.

PMID- 7821361
TI  - Central mechanism of indomethacin analgesia.
AB  - The analgesic effect of indomethacin was investigated by using the visceral pain
      model in rabbits. After intravenous administration of indomethacin (2 mg/kg), the
      maximum increase of the visceral pain threshold was 0.42 +/- 0.31 mA (P < 0.05).
      The analgesic effect lasted 40 min. After intraventricular microinjection of
      indomethacin (50 micrograms), the maximum increase of the visceral pain threshold
      was 0.37 +/- 0.43 mA. After intravenous administration of indomethacin, the
      content of norepinephrine in perfusates of rabbit fourth ventricle was
      significantly increased from 18.10 +/- 8.05 to 32.16 +/- 6.15 mg/40 microliters
      (P < 0.05), compared with data for the control group. The content of beta
      endorphin in the perfusate after indomethacin administration was decreased from 5
      25 min and slightly increased from 25-35 min, compared with the data for the
      control group, but there was no significant difference (P > 0.05). Furthermore,
      intraventricular microinjection of phentolamine (50 micrograms) could block the
      analgesic effect of an intravenous injection of indomethacin, while naloxone
      could not. The results imply that prostaglandins of the central nervous system
      could induce hyperalgesia. Indomethacin injected centrally and peripherally has
      an analgesic effect on visceral pain. This analgesic effect is mediated by alpha
      adrenoceptors. beta-Endorphin does not participate in the analgesic action of
      indomethacin.

PMID- 7821363
TI  - Effect of adrenomedullin on renal hemodynamics and functions in dogs.
AB  - In order to elucidate the role of adrenomedullin in the kidney, we investigated
      the effects of adrenomedullin on renal hemodynamics and urine formation in
      anesthetized dogs. Intrarenal arterial infusion of adrenomedullin (0.8, 4 and 20
      ng.kg-1.min-1) elicited dose-dependent increases in renal blood flow (by 10, 26
      and 37%, respectively) with no change in blood pressure or heart rate, indicating
      a renal vasodilatory action of adrenomedullin. The glomerular filtration rate did
      not increase with the lower two doses, but increased marginally by 9% at the
      highest dose. Infusion of adrenomedullin at the rates of 4 and 20 ng.kg-1.min-1
      increased urine flow and the urinary excretion of sodium and potassium dose
      dependently. Arterial and renal venous plasma renin activity was unaffected by
      adrenomedullin. These findings indicate that adrenomedullin is a potent renal
      vasodilatory peptide with a diuretic action. Since the threshold for the renal
      vasodilatory action of adrenomedullin is close to its physiological concentration
      in human plasma, adrenomedullin may play an important role in the regulation of
      renal function.

PMID- 7821362
TI  - Adenosine A3 receptor stimulation and cerebral ischemia.
AB  - Chronic treatment with the selective adenosine A3 receptor agonist N6-(3
      iodobenzyl)adenosine-5'-N-methylcarboxamide (IB-MECA) administered prior to
      either 10 or 20 min forebrain ischemia in gerbils resulted in improved
      postischemic cerebral blood circulation, survival, and neuronal preservation.
      Opposite effects, i.e., impaired postischemic blood flow, enhanced mortality, and
      extensive neuronal destruction in the hippocampus were seen when IB-MECA was
      given acutely. Neither adenosine A1 nor A2 receptors are involved in these
      actions. The data indicate that stimulation of adenosine A3 receptors may play an
      important role in the development of ischemic damage, and that adenosine A3
      receptors may offer a new target for therapeutic interventions.

PMID- 7821364
TI  - Ca(2+)-inhibition of Ca(2+)-induced small contraction of rat uterine smooth
      muscle.
AB  - Ca2+ has been reported to exert an inhibitory effect on various kinds of smooth
      muscle. The physiological role of this inhibition is unclear. We investigated the
      inhibitory action of Ca2+ on the uterine smooth muscle of the rat in estrus,
      which shows a prominent Ca(2+)-induced inhibition. At concentrations of 0.1-30
      microM Ca2+ inhibited the Ca(2+)-independent contraction of this muscle induced
      by oxytocin in Ca(2+)-free medium. We then investigated the inhibitory action of
      Ca2+ at various concentrations of Ca2+ in the bathing medium and found that Ca2+
      at 1.0-10 microM also inhibited Ca(2+)-dependent contractions, which appeared
      phasically upon the onset of contractions. The magnitude of these phasic
      contractions was inversely proportional to the concentration of Ca2+ (between 1
      10 microM). At 30 microM Ca2+, however, this inhibition was overcome and large
      pendular contractions began. Thus, the inhibition may regulate the initiation of
      smooth muscle contractions. The mechanism of this Ca(2+)-induced inhibition is
      also discussed with regard to an effect on actin.

PMID- 7821365
TI  - Fluoxetine reduces inflammatory edema in the rat: involvement of the pituitary
      adrenal axis.
AB  - The acute effect of the non-tricyclic, pro-serotoninergic, antidepressant drug
      fluoxetine on inflammatory edema was evaluated in the rat. Fluoxetine
      significantly and dose dependently reduced the swelling induced by the injection
      of 10% brewer's yeast suspension in the hindpaw. Both adrenalectomy and
      hypophysectomy prevented the effect of fluoxetine. In contrast pretreatment with
      the corticotropin-releasing hormone antagonist alpha-helical CRH-(9-41) did not
      interfere with the anti-inflammatory action of fluoxetine. Moreover, the drug
      induced a significant increase of corticosterone plasma concentrations in vivo,
      whereas, in vitro, it did not stimulate beta-endorphin release from anterior
      pituitary cells. Our data suggest that fluoxetine exerts a potent anti
      inflammatory action by inducing pituitary-adrenocortical activation via
      serotonin.

PMID- 7821366
TI  - Mechanism underlying nicotine-induced relaxation in dog saphenous arteries.
AB  - In isolated dog saphenous arterial strips denuded of the endothelium, the
      mechanism underlying relaxations induced by nicotine was analyzed. Nicotine
      induced contractions were abolished by treatment with prazosin and alpha,beta
      methylene ATP. In the strips thus treated and contracted with prostaglandin F2
      alpha, nicotine produced a relaxation, which was abolished by hexamethonium. The
      relaxation was inhibited by cyclooxygenase inhibitors and markedly attenuated in
      the strips made tachyphylactic to calcitonin-gene related peptide (CGRP) but not
      to vasoactive intestinal polypeptide. The remaining relaxation in the strips
      treated with indomethacin and CGRP was abolished by NG-nitro-L-arginine, a nitric
      oxide (NO) synthase inhibitor, and the inhibition was reversed by L-arginine but
      not by D-arginine. Perivascular nerves containing NO synthase immunoreactivity
      have been demonstrated in an earlier report. CGRP-immunoreactive nerve fibers
      were observed in the adventitia. It appears that the nicotine-induced relaxation
      is associated with stimulation of vasodilator nerves liberating NO and CGRP, and
      adrenergic neurogenic vasoconstriction predominates over the neurogenic
      vasodilatation in dog saphenous arteries.

PMID- 7821367
TI  - Effect of NE-100, a novel sigma receptor ligand, on phencyclidine-induced
      cognitive dysfunction.
AB  - N,N-Dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]-ethylamine monohydrochloride
      (NE-100) is a selective and potent sigma receptor ligand. We investigated the
      effects of NE-100 on phencyclidine (PCP)-induced cognitive dysfunction in rats in
      a water maze task. NE-100 significantly shortened the PCP-induced prolonged
      swimming latency as did 1-(cyclopropylmethyl)-4-[2'(4"-fluorophenyl)-2'-oxoethyl]
      piperidine monohydrobromide (Dup 734), 4-[2'-(4"-cyanophenyl)-2'-oxoethyl]-1
      (cyclopropyl-methyl)pi peridine (XJ 448), alpha-(4-fluorophenyl)-4-(5-fluoro-2
      pyrimidinyl)-1-piperazine butanol (BMY 14802) and rimcazole, all of which are
      sigma receptor ligands and possibly antagonists. Ritanserin, a 5-HT2 receptor
      antagonist, also showed a tendency to shorten swimming latencies. Latencies of
      haloperidol-, cis-N-(1-benzyl-2-methyl-pyrrolidin-3-yl)-2-methoxy-5-chloro-4-met
      hyl- aminobenzamide (YM-09151-2)- and sulpiride-, dopamine D2 receptor
      antagonists, treated groups did not differ from that seen in the PCP-treated
      group. Thus, PCP-induced cognitive dysfunction may be improved by sigma receptor
      ligands.

PMID- 7821368
TI  - Effects of a novel, selective and potent phosphodiesterase type V inhibitor,
      E4021, on myocardial ischemia in guinea pigs.
AB  - The anti-ischemic effects of a new, selective and potent cyclic 3',5'-guanosine
      monophosphate-specific phosphodiesterase (phosphodiesterase type V) inhibitor,
      sodium 1-[6-chloro-4-(3,4-methylenedioxybenzyl)aminoquinazolin-2-yl ]piperidine-4
      carboxylate (E4021), in a vasopressin-induced guinea pig anginal model were
      examined and compared with those of coronary vasodilators with a guanylate
      cyclase-activating action. An intravenous injection of vasopressin (0.2 IU/kg)
      into anesthetized guinea pigs produced ST segment elevation on the
      electrocardiogram (an index of myocardial ischemia) of 0.28 +/- 0.02 mV (n = 10)
      from the baseline within 30 s. E4021 administered intravenously at doses of 0.03
      and 0.1 mg/kg, 5 min before the injection of vasopressin, significantly inhibited
      the ST segment elevation to 0.15 +/- 0.03 mV (n = 6, P < 0.01) and 0.17 +/- 0.02
      mV (n = 6, P < 0.01), respectively. Three guanylate cyclase activators,
      isosorbide dinitrate (0.1 mg/kg), nicorandil (0.1 mg/kg), and FK409 (0.3 mg/kg),
      also significantly reduced the ST segment elevation to 0.18 +/- 0.03, 0.11 +/-
      0.02 and 0.17 +/- 0.02 mV, respectively. In a second experiment, E4021 was
      administered intraduodenally 30 min before the injection of vasopressin to
      examine its oral effectiveness. Intraduodenal E4021, at doses of 1.0 and 3.0
      mg/kg, also significantly inhibited the ST segment elevation to 0.16 +/- 0.02 mV
      (n = 6, P < 0.01) and 0.13 +/- 0.02 mV (n = 6, P < 0.01), respectively. It is
      concluded that the potent phosphodiesterase type V inhibitor, E4021, administered
      intravenously or intraduodenally, ameliorated myocardial ischemia similarly to
      guanylate cyclase activators. Thus, E4021 may be an orally effective drug in the
      treatment of angina pectoris.

PMID- 7821369
TI  - Platelet aggregation on the endothelium of Schlemm's canal.
AB  - By using monkey eyes and light microscopy, transmission electron microscopy and
      scanning electron microscopy we have studied the role of platelets in Schlemm's
      canal. In eyes connected to a reservoir and subjected to an elevated intraocular
      pressure, there was break-down of the cell membranes facing the invaginations
      into the endothelial cells, resulting in local protrusions from the invaginations
      and ruptures. Other unphysiological openings in the inner wall were due to
      separation of the intercellular junctions. Aggregates of platelets were observed
      at both these types of openings. Small aggregates were observed also in massaged
      eyes and in eyes which had not been touched before fixation. It seems likely that
      the intercellular junctions are fragile, tending to disrupt even under normal
      conditions and that platelets play a role in their repair. It is also suggested
      that platelets tend to restrict the size of the physiological pores.

PMID- 7821371
TI  - Insulin stimulation of retinal outer segment uptake by cultured human retinal
      pigment epithelial cells determined by a flow cytometric method.
AB  - This study investigates the mechanism by which insulin stimulates phagocytosis in
      cultured human retinal pigment epithelium, using a flow cytometric assay of
      retinal outer segment uptake. RPE cells were isolated from adult human donors and
      grown in culture. Retinal outer segments were isolated from fresh bovine eyes and
      covalently labeled with the fluorescent dye carboxy-SNAFL-2. Retinal outer
      segment binding and uptake was quantified by direct visualization and the
      increase in cellular fluorescence measured using a flow cytometer and the methods
      compared. Uptake measured by flow cytometry was further characterized by
      concentration, time, temperature and serum stimulation, and shown to be
      comparable to other published methods. Uptake of retinal outer segments was
      acutely stimulated by insulin in the absence or presence of serum with half
      maximal stimulation occurring between 0.1 and 1.0 microgram ml-1. Theophylline,
      forskolin and cholera toxin all reduced retinal outer segment uptake by RPE
      cells, but had no effect upon insulin stimulation. Measurements of cAMP showed
      that insulin did not change intracellular cAMP concentration compared to controls
      in the absence or presence of added retinal outer segments. One hundred nanomolar
      okadaic acid also inhibited retinal outer segment uptake but not insulin
      stimulated uptake, nor did 100 microM genistein have an effect upon insulin
      stimulated uptake. Preincubation of RPE cells with 25 microM ZnCl2 overnight
      stimulated retinal outer segment uptake and appeared to inhibit the insulin
      stimulation. Preincubation of the cells in 25 mM glucose overnight also increased
      the uptake of retinal outer segments over control and reduced the effect of
      insulin. We conclude that insulin stimulates retinal outer segment phagocytosis
      by an as yet unknown process which may involve specific tyrosine phosphatases.

PMID- 7821370
TI  - Characterization and novel activation of 72-kDa metalloproteinase in retinal
      interphotoreceptor matrix and Y-79 cell culture medium.
AB  - Analysis of bovine interphotoreceptor matrix and conditioned medium from human Y
      79 retinoblastoma cells by gelatin SDS-PAGE zymography reveals abundant activity
      of a 72-kDa M(r) gelatinase. The 72-kDa gelatinase from either source is
      inhibited by EDTA but not aprotinin or NEM, indicating that it is a
      metalloproteinase (MMP). The 72-kDa MMP is converted to a 62-kDa species with
      APMA treatment after gelatin sepharose affinity purification, typical of
      previously described gelatinase MMP-2. The latent 72-kDa gelatinase from either
      bovine IPM or Y-79 media autoactivates without APMA in the presence of calcium
      and zinc after 72 hr at 37 degrees C, producing a fully active mixture of
      proteinase species, 50 (48 in Y-79 medium), 38 and 35 kDa in size. The presence
      of inhibitory activity was examined in both whole bovine IPM and IPM fractions
      separated by SDS-PAGE. Whole IPM inhibited gelatinolytic activity of
      autoactivated Y-79-derived MMP in a dose-dependent manner. Inhibitory activities
      are observed in two protein fractions of 27-42 and 20-25 kDa. Western blots using
      antibodies to human tissue inhibitor of metalloproteinase 1 and 2 (TIMP-1 and -2)
      reveal the presence of two TIMP-1-like proteins at 21 and 29 kDa in inhibitory
      fractions of the bovine IPM. TIMP-2 was not detected in the inhibitory IPM
      fractions, consistent with the observed autoactivation of bovine IPM 72-kDa
      gelatinase. Potential roles for this IPM MMP-TIMP system include physiologic
      remodelling of the neural retina-RPE cell interface and digestion of shed rod
      outer segment as well as pathological processes such as retinal detachment, PE
      cell migration, neovascularization and tumor progression. Cultured Y-79 cells
      appear to be a good model for studying the production and regulation of this
      proteinase system.

PMID- 7821372
TI  - Embryonic rabbit retinal transplants survive and differentiate in the choroid.
AB  - Retinal allotransplants to intraocular locations usually survive well, partly
      because of the relative immune privilege provided by the blood-ocular barriers.
      The choroid, however, is located outside the barriers, and is therefore usually
      considered not to be immunologically privileged. This study was performed to
      investigate if transplants could survive in the choroid, and, if so, if they
      develop some sort of blood transplant barrier. Embryonic retinas from pigmented
      rabbits at stage E 15 (embryonic day 15) or E 22 were dissected and transplanted
      into the choroid of 29 adult animals of the same strain. As controls, a similar
      retinal transplant was placed in the subretinal space in six animals and in the
      subconjunctival space in another six animals. The animals were killed at
      intervals up to 8 weeks and the eyes were analysed by light microscopy,
      immunohistochemistry and morphometry. Some of the animals received Evan's Blue
      intravenously before termination. Eighty-three per cent of the choroidal
      transplants survived until termination. All six subretinal but none of the six
      subconjunctival transplants survived. Both choroidal and subretinal grafts
      developed rosettes, i.e. rounded formations of retinal cells organized in layers.
      The different retinal cells developed normal reactivity for the intracellular
      markers rhodopsin, neurofilament 160 kDa, vimentin and GFAP. Evan's Blue and
      endogenous serum albumin were used as markers for the patency of the blood-ocular
      barriers. Evan's Blue was not excluded from the transplants in the early phase up
      to day 8 after the transplantation. The Evan's Blue content diminished with
      longer survival times, and after 40 days almost no Evan's Blue was present in the
      transplants.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7821374
TI  - Characterization and functional activity of dendritic cells from rat choroid.
AB  - Cell preparations from the posterior eye cup of the eye cultured for 2 days
      exhibited accessory activity for T-cell responses to a mitogenic treatment and
      stimulatory activity in a mixed leukocyte reaction (MLR), two functions
      characteristic of dendritic cells (DC). These activities both partitioned with
      cells having a low buoyant density, another characteristic of DC. Immunomagnetic
      separations with monoclonal antibodies against lymphoid dendritic cell surface
      antigens revealed that the accessory activity of the low-density cells was
      entirely associated with a small population of cells positively selected by these
      antibodies. Immunofluorescent staining with these same antibodies also revealed a
      small subpopulation of low-density cells having the morphology of DC. On cryostat
      sections of eye tissue the positively-stained cells were localized in the choroid
      and were not observed within the sclera or the retina. Based on these results we
      conclude that there are functional DC in the choroid, and we speculate that they
      may have a significant role in the inflammatory process during posterior uveitis.

PMID- 7821373
TI  - Modulating radiation cataractogenesis by hormonally manipulating lenticular
      growth kinetics.
AB  - There is considerable evidence that the lens epithelium is the primary site of
      injury leading to the development of cataracts following radiation exposure. That
      the damaged cells of the epithelium are the progenitors of the aberrantly
      differentiating fibers associated with the cataract is indisputable. So too is
      the observation that post-radiation proliferative activity in the lens epithelium
      is required for cataracts to develop. The natural hormonal regulation of lens
      epithelial mitotic activity in the frog offers the opportunity to alter the cell
      cycle of the lens epithelium in vivo, thus enabling the direct examination of the
      role of lenticular mitosis in the cytopathomechanism of radiation-induced
      cataracts. The cell cycle of the lens epithelium of northern leopard frogs was
      manipulated by hypophysectomy (to halt mitotic activity) and pituitary hormone
      administration (to stimulate baseline mitosis and reverse hypophysectomy-induced
      mitotic suppression). Animals were hypophysectomized, irradiated and injected
      with pituitary hormone replacement. Irradiated animals, irradiated animals +
      hormone replacement and irradiated hypophysectomized animals served as controls.
      Cataract development was evaluated by slit-lamp biomicroscopy and correlated with
      histologic determinations of mitotic index and meridional row disorganization on
      lens epithelial whole mounts. In another study, hypophysectomized-irradiated
      animals received varying concentrations of replacement hormone in an attempt to
      quantitatively modulate lens epithelial mitotic activity and determine the effect
      on cataractogenesis. It was found that irradiated-hypophysectomized (mitosis
      halted) frogs failed to develop opacities, while those with hormonal replacement
      (mitosis reinstated) developed cataracts.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7821375
TI  - Electrophysiological properties of cultured human trabecular meshwork cells.
AB  - Previous studies using cultured bovine trabecular meshwork cells demonstrated at
      least two different cell types which were distinguishable morphologically and
      electrophysiologically. The purpose of the present study was to evaluate the
      electrical membrane properties of cultured human trabecular meshwork cells. Seven
      different human trabecular meshwork cell lines were grown from four different
      donors. One trabecular meshwork cell line was transformed by microinjection with
      SV40 DNA. The electrochemical properties of these TM cells were determined by
      micropuncture with glass microelectrodes. The mean membrane voltage at resting
      conditions differed between the cell lines (-33.3 to -58.7 mV). Application of 10
      mmol l-1 Ba2+ induced repetitive voltage spikes in all cell lines. The voltage
      transients similar to action potentials were inhibited by nifedipine, but
      insensitive to tetrodotoxin. Acetylcholine evoked depolarizations in three cell
      lines which were blocked by atropine. In one cell line isoproterenol caused
      sustained depolarizations sensitive to metipranolol. All three of the cell lines
      tested depolarized upon application of the vasoactive peptide endothelin-1. All
      untransformed cell lines showed voltage spikes typical for smooth muscle cells
      and functional receptors for endothelin-1 and cholinergic agonists. One out of
      three cell lines tested possessed beta-adrenergic receptors influencing the
      membrane voltage.

PMID- 7821376
TI  - Lipoxygenases in corneal epithelia of man and cynomolgus monkey.
AB  - Human and monkey corneal epithelia were investigated for lipoxygenases. The low
      speed supernatant of human corneal epithelium converted arachidonic acid to one
      prominent metabolite, which was identified as 15-hydroxyeicosatetraenoic acid by
      gas chromarography mass spectrometry and by ultra violet analyses.
      Eicosatetraynoic acid, a lipoxygenase inhibitor, reduced the formation of 15
      hydroxyeicosatetraenoic acid, by 90% at 30 microM, while esculetin (30 microM)
      and diclofenac (100 microM) did not inhibit the biosynthesis. Immunohistochemical
      analysis of human cornea using a polyclonal antibody against recombinant human
      reticulocyte 15-lipoxygenase showed staining of the epithelium, but not the
      stroma. The cytosolic fraction of epithelial cells of the monkey, Macaca
      fascicularis, converted [1-14C]arachidonic acid to two major metabolites, which
      were identified as 15S-hydroxyeicosatetraenoic and 12S-hydroxyeicosatetraenoic
      acids by cochromatography with these compounds on reverse-phase, straight-phase
      and chiral high-performance liquid chromatography. Lipoxygenase activity could
      not be detected in the microsomal fraction. The results provide biochemical,
      pharmacological and immunohistological evidence of a 15-lipoxygenase in human
      corneal epithelium and suggest that monkey corneal epithelium contains cytosolic
      12- and 15-lipoxygenases.

PMID- 7821377
TI  - Transforming growth factor beta 2 is the predominant isoform in the neural
      retina, retinal pigment epithelium-choroid and vitreous of the monkey eye.
AB  - Several techniques were utilized to assess the levels, disposition and cellular
      sources of isoforms 1 and 2 of transforming growth factor beta (TGF-beta) in the
      posterior pole of the monkey eye. Freshly dissected tissues, as well as the
      saline vehicles in which dissections were performed, were analysed by sandwich
      enzyme-linked immunosorbent assay. In all tissues TGF-beta 2 was the predominant
      isoform, with beta 2:beta 1 ratios of 6:1 for neural retina (as ng g-1) and 425:1
      for vitreous (as pmol l-1). Retinal pigment epithelium (RPE)-Bruch's membrane
      choroid complex contained approximately 10 times the amount of both TGF-beta
      isoforms as neural retina. For first passage cultures of monkey RPE, TGF-beta 2,
      but not TGF-beta 1, accumulated over time in conditioned media samples.
      Immunoreactivity for TGF-beta 2 was detected both in tissue sections of posterior
      pole, specifically in rod outer segments and RPE, and also in the first passage
      cultures of RPE. Antibodies to specific peptide sequences of both isoforms
      localized TGF-beta to the outer segments of rod photoreceptors. The apparent
      sequestration of TGF-beta 2 in photoreceptor outer segments, as well as the in
      vitro evidence for possible synthesis and release by RPE, suggest that TGF-beta 2
      is an important modulator of visual function acting at the retina-RPE interface.

PMID- 7821378
TI  - Expression of c-jun proto-oncogene in corneal endothelium.
AB  - The cellular proto-oncogenes are important for proliferation, differentiation and
      transformation. To study growth regulation of bovine corneal endothelium (BCE),
      the authors examined the effect of serum on the expression of the c-jun proto
      oncogene in these cells. Increased expression of both c-jun protein and c-jun
      mRNA was found. This response was transient. While the mRNA reached maximum
      levels at 45 min, c-jun protein levels peaked around 2 hr and declined
      thereafter. The peptide growth factors, basic fibroblast growth factor (FGF-2),
      insulin and transforming growth factor beta 1 (TGF beta 1), which are mitogenic
      in BCE, were found to effect c-jun protein expression differentially. Basic
      fibroblast growth factor and 20% fetal calf serum were very effective in inducing
      c-jun protein expression (in 81% +/- 5.2, 73% +/- 3.4 of cells, respectively),
      while insulin and TGF beta 1 were less effective (47% +/- 8.0, 32% +/- 4.3,
      respectively). Since c-jun protein has been shown to be important for cell cycle
      progression in fibroblasts, our data indicate that it may play a similar role in
      corneal endothelial cells. Thus, c-jun can be used as an indicator of growth
      regulatory activity in corneal endothelial cells and further analysis of its
      regulation will contribute to our understanding of the underlying control
      mechanisms in these cells.

PMID- 7821379
TI  - Na(+-) Cl(-)- and HCO3(-)-dependent base uptake in the ciliary body pigment
      pigment epithelium.
AB  - Segments of whole ciliary body dissected from Dutch belted rabbits were incubated
      for 60 min at 36 degrees C in a 30 microM Ca2+ Ringer's. The inner limiting
      membrane with its adherent non-pigmented epithelium then was mechanically removed
      from the surface. The newly-exposed viable layer of pigmented cells was then
      loaded with the fluorescent probe 2'-7'-bis (carboxymethyl)-5(6)
      carboxyfluorescein by incubating the segments for 45 min at RT with the cell
      permeable acetoxymethoxy form of the dye. These loaded tissues were perfused in a
      flow-through chamber, mounted on the heated stage of a microscope equipped for
      quantitative epifluorescence, and the intracellular pH (pHi) of small groups of
      cells was derived from the ratio of emission intensities generated by excitations
      at 490 and 440 nm, respectively. In N[2-hydroxyethyl] piperazine-N"-[2 ethane
      sulfonic acid](Hepes)-buffered Ringer's the intracellular pH was 7.23 +/- 0.21
      (+/- S.D., n = 20). Replacement of 28 mM Hepes by 28 mM HCO3-/5% CO2 led to a
      0.14 +/- 0.04 increase in pHi. This increase required the presence of Na+ and Cl-
      and was inhibited by 0.2 mM diisothiocyanatostilbene-2-2'-disulfonic acid. These
      observations as well as characteristic pHi, responses to the removal or
      introduction of Na+ or Cl- indicated the presence in the pigmented cells of a
      Na(+)- and Cl(-)-dependent HCO3- transporter responsible for base uptake.

PMID- 7821380
TI  - The glucose transporter in the plasma membrane of the outer segments of bovine
      retinal rods.
AB  - The facilitated diffusion glucose transporter in the plasma membrane of intact
      outer segments isolated from bovine retinal rods (ROS) was characterized by
      measurements of: (1) 14C-labeled 3-O-methylglucose fluxes; and (2) glucose
      sensitive binding of 3H-labeled cytochalasin B to ROS membranes. Inhibition of 3
      O-methylglucose influx into ROS, inhibition of 3-O-methylglucose efflux from ROS
      and glucose-sensitive binding of cytochalasin B to ROS showed very similar
      cytochalasin B inhibition/dissociation constants of 0.9 microM, 1.3 microM and
      1.3 microM, respectively. D-glucose inhibited both 14C-labeled 3-O-methylglucose
      transport and cytochalasin B binding. The above results suggest that D-glucose
      sensitive cytochalasin B binding reflects specific binding to the ROS glucose
      transporter and the density of glucose transporter in the ROS plasma membrane was
      determined to be 800 microns-2, comparable to relatively abundant ROS plasma
      membrane proteins such as the cGMP-gated channel and the Na-Ca+K exchanger.
      Displacement of 3H-labeled cytochalasin B by non-transportable hexoses was used
      to localize the hexose transporters to the ROS plasma membrane and to examine a
      simple single-site, alternating conformation model for hexose transport. A
      comparison between the Glut1 glucose transporters of bovine ROS, bovine
      erythrocytes and human erythrocytes suggests that kinetic and pharmacological
      characteristics of glucose transporters cannot be predicted in a simple manner
      from gene type and species.

PMID- 7821381
TI  - Calpains in lens epithelium from patients with cataract.
AB  - Lens epithelium from patients with cataract was obtained during surgery and
      frozen. The samples were subjected to SDS-electrophoresis and Western blotting.
      Calpains were quantified using polyclonal antibodies against m- and mu-Calpain
      could be detected but not the isoenzyme mu-calpain, indicating that m-calpain is
      the significant most important calpain in human lens epithelium. Quantification
      of m-calpain showed no relationship to age or gender, but there were significant
      differences between different types of cataract.

PMID- 7821382
TI  - Molecular characterization of the alpha'-subunit of cone photoreceptor cGMP
      phosphodiesterase in normal and rd chicken.

PMID- 7821383
TI  - The predominant cadherin in fetal human lens is identical to N-cadherin and is
      not a candidate locus for the Marner cataract.

PMID- 7821384
TI  - In vivo release of catecholamines from xenogeneic chromaffin cell grafts with
      antidepressive activity.
AB  - Previous studies in our laboratory have demonstrated that allografts of adrenal
      medullary tissue and xenografts of isolated bovine chromaffin cells to the rat
      frontal cortex can increase antidepressive activity in two separate animal
      models. Biochemical and pharmacological evidence suggest that the most likely
      mechanism of these antidepressive effects is via local release of catecholamines
      into the surrounding cortical parenchyma. The aim of the present study was to
      directly characterize the antidepressive mechanism of chromaffin cell xenografts
      by utilizing in vivo microdialysis to measure extracellular catecholamine levels
      from bovine chromaffin cell and control implanted rat frontal cortex. Following
      transplantation, only bovine chromaffin cell grafted rats displayed significant
      increases in antidepressive activity, as assessed by the forced swimming test,
      compared to rats with grafts of bovine adrenal medullary fibroblasts or
      nontransplanted rats. In vivo microdialysis results revealed remarkably elevated
      levels of epinephrine (EPI) and norepinephrine (NE), but not dopamine, in
      dialysates from bovine chromaffin cell-transplanted frontal cortex. The most
      likely source of these enhanced EPI and NE levels is the grafted xenogeneic
      chromaffin cells. The results of this study directly demonstrate that xenografts
      of bovine chromaffin cells to the rat frontal cortex provide a releasable pool of
      catecholamines for antidepressive activity.

PMID- 7821385
TI  - Early reduction in insulin-like growth factor gene expression in diabetic nerve.
AB  - Diabetic neuropathy is a common and disabling complication of diabetes mellitus
      whose pathogenesis remains unknown. Insulin-like growth factors (IGFs) have been
      recently implicated in the development and maintenance of the peripheral nervous
      system, and circulating IGF levels are decreased in experimental and clinical
      diabetes. Therefore, we tested the hypothesis that IGF gene expression is reduced
      in peripheral nerves early after the onset of diabetes. Sciatic nerves from
      nondiabetic and streptozotocin-treated rats were removed 5-7 days after the
      induction of diabetes. RNA was isolated and analyzed by Northern and slot blots.
      IGF-I mRNA content was significantly decreased per milligram wet weight nerve (P
      < 0.025) as well as per poly(A)+ RNA (P < 0.01) in diabetic vs nondiabetic
      nerves. Likewise, the amount of IGF-II mRNA was significantly decreased per
      milligram wet weight nerve (P < 0.01) as well as per poly(A)+ RNA (P < 0.005).
      These effects were selective because histone 3.3 mRNA content, as well as
      poly(A)+ mRNA content, per milligram nerve were unchanged. Insulin treatment
      partially prevented this decline in IGF-I and IGF-II mRNA levels. The diminished
      IGF mRNA content is one of the earliest biochemical abnormalities to be observed
      in the diabetic nerve, supporting the hypothesis that a reduction in IGF activity
      in diabetic nerves precedes and contributes to the development of neuropathy.

PMID- 7821387
TI  - Neurite degeneration elicited by apolipoprotein E peptides.
AB  - Apolipoprotein E (apoE) has been localized to the neurofibrillary tangles and
      beta-amyloid-containing plaques found in the cortex of patients with Alzheimer's
      disease (AD) (14, 28), suggesting that apoE may play a role in this disorder.
      Recently, synthetic peptides containing a sequence within apoE (amino acids 141
      155) were found to be cytotoxic to T lymphocytes in culture. In the present
      study, tandem presentation of the apoE sequence E141-155, as well as longer
      monomeric peptides that include this domain, was found to cause extensive and
      specific degeneration of neurites from embryonic chick sympathetic ganglia in
      vitro. These results, together with the observation of strong beta A4/apoE
      binding in vitro and the disproportionate occurrence of the epsilon 4 allele in
      both familial and sporadic AD patients, suggest that peptide sequences associated
      with apoE may contribute directly to neurodegenerative processes.

PMID- 7821386
TI  - Specific regeneration of cutaneous sensory afferent fibers in the amphibian
      spinal cord.
AB  - Regeneration of cutaneous sensory fibers within the spinal cord was studied in
      frogs after lesions of sensory axons in dorsal roots. Sensory fibers were
      disrupted by repeatedly freezing the exposed brachial dorsal root in
      postmetamorphic frogs. Previous experiments indicated that this procedure
      destroyed virtually all sensory axons within the dorsal root. The pattern of
      regrowth of these fibers within the spinal cord was then assessed at different
      times by labeling them with horseradish peroxidase applied to the superior
      cutaneous ulnar nerve in the front leg. Arborizations of cutaneous axons within
      the spinal gray matter were remarkably similar to those in normal frogs. The
      arborizations were restricted to dorsal levels of the cord, never projecting
      ventrally to the region where muscle spindle sensory axons terminate. These
      experiments complement earlier studies demonstrating that muscle spindle
      afferents also regenerate specifically. Together these studies indicate that
      sufficient cues exist in the mature amphibian spinal cord to allow different
      classes of sensory fibers to reinnervate their appropriate target areas.

PMID- 7821388
TI  - Specific patterns of defective HSV-1 gene transfer in the adult central nervous
      system: implications for gene targeting.
AB  - Viral vectors are a means by which genes can be delivered to specific sites in
      the adult central nervous system. Nevertheless, the interaction between the viral
      vector and cells of the nervous system, which forms the basis for specific gene
      transfer, is not well understood. In this study a nonreplicating defective herpes
      simplex virus type 1 vector, expressing the marker gene lacZ, was stereotaxically
      injected at varying titers into the rat central nervous system. Three sites were
      targeted: the caudate nucleus, dentate gyrus, and cerebellar cortex, and the
      resulting patterns of beta-galactosidase activity were examined. Many cells of
      neuronal and glial morphology, and of differing neuronal subtypes, expressed beta
      galactosidase at each of the injection sites. However, beta-galactosidase
      activity was also detected in distant secondary brain areas, the neurons of which
      make afferent connections with the primary sites. This strongly suggested that
      the retrograde transport of defective virus was the basis for the enzyme activity
      observed at a distance. Moreover, retrograde transport to secondary sites was
      found to be highly selective and restricted to certain retrograde neuroanatomical
      pathways in a specific and titer dependent fashion. The pathways observed were
      predominantly, but not exclusively, monoaminergic in origin. This finding is
      supported by reports of specific tropism by HSV for monoaminergic circuits in
      experimental encephalitis and transneuronal tracing studies. Our observations
      suggest that certain functional neuronal populations, which are permissive for
      the retrograde transfer of defective HSV-1 vectors, might be specifically
      targeted for gene transfer using this approach. Conversely, a knowledge of the
      pathways permissive for viral uptake, retrograde transfer, and subsequent gene
      expression will be essential in order to predict the consequences of gene
      transfer using viral vectors.

PMID- 7821389
TI  - Implantation of polymer-encapsulated human nerve growth factor-secreting
      fibroblasts attenuates the behavioral and neuropathological consequences of
      quinolinic acid injections into rodent striatum.
AB  - Delivery of neurotrophic molecules to the central nervous system has gained
      considerable attention as a potential strategy for the treatment of neurological
      disorders. In the present study, a DHFR-based expression vector containing the
      human nerve growth factor gene (hNGF) was transfected into a baby hamster
      fibroblast cell line (BHK). Using an immunoisolatory polymeric device,
      encapsulated BHK-control cells and those secreting hNGF (BHK-hNGF) were
      transplanted unilaterally into rat lateral ventricles. Three days later, the same
      animals received unilateral injections of quinolinic acid (QA, 225 nmol) or the
      saline vehicle into the ipsilateral striatum. Approximately 2 weeks following
      surgery, animals were tested for apomorphine-induced rotation behavior. Animals
      which received BHK-hNGF cells rotated significantly less than those animals
      receiving BHK-control cells or QA alone. Histological analysis 29-30 days
      following capsule implantation demonstrated that BHK-hNGF cells attenuated the
      extent of host neural damage produced by QA as assessed by a sparing of ChAT- and
      NADPH-d-positive neurons. Moreover, a lessened GFAP reaction was apparent within
      the striatum of animals receiving BHK-hNGF cells. As measured by ELISA, hNGF was
      released by the encapsulated BHK-hNGF cells prior to implantation and following
      removal. Morphology of retrieved capsules revealed numerous viable and
      mitotically active BHK cells. These results suggest that implantation of polymer
      encapsulated hNGF-releasing cells can be used to protect neurons from excitotoxin
      damage.

PMID- 7821390
TI  - Nerve growth factor influences the distribution of sympathetic sprouting into the
      hippocampal formation by implanted superior cervical ganglia.
AB  - Following cholinergic denervation of the hippocampal formation, peripheral
      sympathetic fibers from the superior cervical ganglion (SCG) sprout into
      hippocampal tissue. The molecular mechanism controlling this process is unknown,
      although a role by trophic factors seems likely. In the present study, neonatal
      SCG were used as biological probes to investigate the association between NGF
      immunoreactive regions in the hippocampal formation and areas innervated by
      regrowing sympathetic fibers. Cholinergic deafferentation of the hippocampal
      formation was achieved by a fimbria-fornix transection and neonatal SCG were
      placed into the lesion cavity, abutting the rostral pole of the hippocampus. At
      16 days following ganglia transplantation, NGF immunoreactivity within the
      hippocampal formation appeared indistinguishable from unlesioned controls and was
      localized within the mossy fiber region of the dentate gyrus and CA3 and CA2
      hippocampal subfields. Sympathetic innervation, revealed in adjacent sections by
      dopamine beta-hydroxylase or p75LNGFR immunoreactivity, was also restricted
      primarily to the mossy fiber region. Ablation of the entorhinal cortex at the
      time of transplantation resulted in the appearance of an additional discrete band
      of NGF immunoreactivity within the outer molecular layer of the dentate gyrus. In
      animals receiving an entorhinal lesion concurrent with the SCG transplant,
      sympathetic fibers were observed not only within the mossy fiber region but also
      within the outer molecular layer of the dentate gyrus where the lesion-induced
      NGF immunoreactivity appeared. These results support the hypothesis that
      topographic distributions of NGF may be used in the hippocampal formation to
      define terminal fields for sprouting NGF-sensitive neuronal populations.

PMID- 7821391
TI  - Cytoarchitectonic development, axon-glia relationships, and long distance axon
      growth of porcine striatal xenografts in rats.
AB  - Porcine fetal lateral ganglionic eminence cells were transplanted into the
      quinolinic-acid-lesioned corpus striatum of immunosuppressed adult rats. The
      resulting grafts were analyzed for graft development with respect to donor age,
      donor cell dosage, and survival time from 5 to 22 weeks postimplantation. Graft
      development is prolonged by a factor of 3-4 times in porcine xenografts as
      compared to rat allografts. As grafts matured, neuronal somata developed in
      clusters that expressed acetylcholinesterase (AChE), tyrosine hydroxylase, and
      dopamine- and cAMP-associated phosphoprotein. These clusters were interspersed
      with AChE-poor graft regions consisting of small densely packed cells that
      stained for glial fibrillary acidic protein and porcine cluster of
      differentiation factor 44 (a species-specific glial marker). Graft axons could be
      selectively stained for 70-kDa neurofilament and were preferentially associated
      with AChE-poor, glial-rich regions in younger grafts (8 weeks), but AChE-rich
      neuronal regions in older grafts (22 weeks). Both graft axons and graft glial
      fibers projected for long distances into the host internal capsule, external
      capsule, corpus callosum, and anterior commissure. Donor axons also innervated
      host target structures including the globus pallidus and substantia nigra. This
      demonstrates a prolonged development of striatal cells that is appropriate to the
      donor species and which produces long-distance target-specific axonal growth
      within the adult host brain.

PMID- 7821392
TI  - Increased nerve growth factor level in the distal stump of transected sciatic
      nerve in relation to aging and its application for neural grafting.
AB  - The nerve growth factor (NGF) level in the distal stump of mouse sciatic nerve
      transected 24 h before increased significantly compared with that in the
      nontransected contralateral side. This level was higher in aged (24-month-old)
      mice than in aging (12-month-old) or in young (1-month-old) mice. Adrenal
      medullary tissue mixed with the pretransected (24 h before) distal stump of the
      sciatic nerve of aged mice was cografted into the ipsilateral striatum of aged
      mice with a unilateral 6-hydroxydopamine lesion of dopaminergic system. Two and 4
      weeks after transplantation, cografted mice showed partial functional
      compensation in amphetamine-induced motor asymmetry while mice with adrenal
      grafts alone did not show the functional recovery. The immunocytochemical
      staining of tyrosine hydroxylase revealed large numbers of chromaffin cells
      surviving in cografted animals. It is concluded that NGF level in the distal
      stump of pretransected peripheral nerve is increased even in aged animals and
      cografting of this nerve stump with adrenal medulla can be effectively utilized
      in aged animals with nigrostriatal insufficiency.

PMID- 7821393
TI  - Axonal transport of endogenous nerve growth factor (NGF) and NGF receptor in
      experimental diabetic neuropathy.
AB  - There is increasing evidence that deprivation of the retrogradely transported
      neurotrophic protein nerve growth factor (NGF) accounts for some functional
      deficits known to occur in experimental diabetic neuropathy. Here we have studied
      changes in the axonal transport of endogenous NGF, NGF receptor (NGFR), and NGFR
      saturation (NGF/NGFR ratio) in the rat sciatic nerve after 2 months of
      streptozotocin (STZ)-induced diabetes mellitus. Compared with vehicle-treated
      control rats (blood glucose: 6-12 mM), there was a very clear reduction in the
      retrograde transport of NGF by 50% (P < 0.001) in STZ-treated, diabetic animals
      (blood glucose: 33-62 mM). No significant reduction in NGF axonal transport was
      observed in a subpopulation of STZ-treated rats (poor responders) with nearly
      normal glucose levels (range: 9-12 mM). No change was observed in any group in
      the retrograde transport of NGFR. Compared with control rats, however, the
      apparent NGFR saturation was reduced by 45% (P < 0.002) in STZ diabetics, whereas
      no change in NGFR saturation was observed in the STZ-poor responders. Moreover,
      the NGFR saturation and amount of retrogradely transported NGF were negatively
      correlated to the individual glucose concentration in diabetics (r2 = 0.47 and
      0.55, respectively; P < 0.0001). These findings indicate that, while NGFR
      expression is normal in the STZ-diabetic neuropathy model, the marked decrease in
      receptor saturation observed in diabetics may reflect low peripheral NGF levels,
      which in consequence leads to the apparent deprivation of neuronal NGF in
      diabetic rats.

PMID- 7821394
TI  - The neurotrophins NT-4/5 and BDNF augment serotonin, dopamine, and GABAergic
      systems during behaviorally effective infusions to the substantia nigra.
AB  - Brain-derived neurotrophic factor (BDNF) and neurotrophin-4/5 (NT-4/5) have both
      been identified as ligands for the TrkB receptor, yet differences have emerged in
      terms of their in vitro potencies for neuronal survival and differentiation. This
      has prompted the in vivo study of their effects on behavior and neuro-chemical
      parameters associated with dopamine, serotonin, and GABAergic neurons in the
      basal ganglia. Two-week supranigral infusions of NT-4/5 and BDNF were similar in
      their ability to augment levels of the dopamine metabolite homovanilic acid (HVA)
      (63 and 78%, respectively) and the ratios of dihydroxphenylacetic acid/dopamine
      (DOPAC/DA) (39, 48%) and HVA/DA (85, 77%) in the caudate-putamen of the
      hemisphere ipsilateral to the nigral infusion. Striatal concentrations of DOPAC
      were elevated 45% by BDNF but not by NT-4/5. The 3-MT/dopamine ratio, an
      indicator of dopamine release, was elevated by 38 and 32% in the striata of BDNF-
      and NT-4/5-infused rats, respectively. Striatal indoleamine metabolism,
      determined by the ratio of 5-hydroxyindoleacetic acid (5HIAA)/serotonin was also
      elevated by NT-4/5 and BDNF in the caudate-putamen (29, 32%), and the 5HIAA
      content of the substantia nigra was elevated by both factors (43, 40%). The
      activity of GAD within the superior colliculus was elevated 21 and 41% by BDNF
      and NT-4/5, respectively. A contraversive rotational bias was induced in BDNF and
      NT-4/5-treated rats challenged with d-amphetamine, and these responses were
      blocked by pretreatment with selective D1 or D2 receptor antagonists but not by
      opiate receptor antagonism. Thus, NT-4/5 and BDNF can elevate the turnover of
      dopamine through both metabolic and release pools and augment the behavioral
      response to d-amphetamine. The role for dopamine in this behavioral response is
      indicated by the requirement of unoccupied D1 and D2 receptors, but may also
      involve changes in serotonergic, GABAergic, or other pathways. The TrkB receptor
      specific actions of BDNF and NT-4/5 may have implications for understanding the
      etiology or treatment of basal ganglia disorders.

PMID- 7821395
TI  - Studies of myelin formation after transplantation of human Schwann cells into the
      severe combined immunodeficient mouse.
AB  - We have previously demonstrated (J. Neurosci., 14: 1309-1319) that Schwann cells
      (SCs) isolated from adult human peripheral nerve in tissue culture and then
      transplanted into an immune-deficient rat can enhance axonal regeneration and
      myelinate regenerating peripheral axons. We have now (a) compared the capacity of
      both primary and expanded populations of cultured human SCs to form myelin around
      regenerating mouse axons when transplanted into a gap within the sciatic nerve of
      severe combined immunodeficiency (scid) mice and (b) also compared the
      myelinating capability of these cultured SCs to their counterparts in the native
      human peripheral nerve xenograft. Schwann cells were isolated from adult human
      peripheral nerve. Semipermeable guidance channels were filled with a 30% Matrigel
      solution mixed with either primary human SCs or human SCs expanded with mitogens
      both at a density of 120 million cells/ml. These channels or a human peripheral
      nerve xenograft were implanted within a 5-mm gap in the transected sciatic nerve
      of the scid mice and analyzed after a period of 6 weeks. The presence of human
      myelin segments was confirmed in both the guidance channels containing human SCs
      and the xenografts by immunostaining with a monoclonal antibody (592) which
      specifically recognizes a prominent myelin component, P0, in the human but not in
      the mouse. Within both the guidance channels and the xenografts there was an
      invasion of the transplant by host SCs which went on to form myelin around
      regenerating mouse axons. In this report, we also demonstrate that human SCs that
      have been expanded in culture with mitogens are capable of forming myelin after
      transplantation in this experimental paradigm.

PMID- 7821396
TI  - Sources of human Schwann cells and the influence of donor age.
AB  - We evaluated several tissues as possible sources for culturing human Schwann
      cells. The average cell yield (total cell number/mg of nerve fascicle) obtained
      from adult autopsy cases and transplant organ donors was similar (2 x 10(4) and
      2.9 x 10(4), respectively), but significantly higher yields were obtained from
      dorsal roots of pediatric patients undergoing selective dorsal rhizotomy (6.1 x
      10(4)). Fresh tissue was not essential since cells isolated from 0 to 20 h
      postmortem were equally viable. However, we found evidence that donor age affects
      the intrinsic growth rate of Schwann cells and perineurial fibroblasts in
      culture.

PMID- 7821397
TI  - Regional differences in reactive gliosis induced by substrate-bound beta-amyloid.
AB  - Regions of gliosis surround deposits of beta-amyloid peptide (beta AP) in senile
      plaques of Alzheimer's disease (AD). The association between reactive astrocytes
      and beta AP in senile plaques is most pronounced in cortex and hippocampus but
      not at other anatomical sites of beta AP deposition. We hypothesized that this
      region-specific pathology in AD could be attributed to differences in glial
      reactivity in different parts of the central nervous system (CNS). To test this
      hypothesis, we assayed astrocytes from cerebral cortex, hippocampus, cerebellum,
      and spinal cord for cellular responsiveness to substrate-bound beta AP in vitro.
      Astrocyte reactivity was monitored by morphological changes, increased deposition
      of chondroitin sulfate proteoglycan-containing matrix, and alterations in
      proteoglycan metabolism. Based on these criteria, only cortical and hippocampal
      astrocytes showed marked reactivity to immobilized beta AP. In cortical and
      hippocampal cultures only, immobilized beta AP resulted in increased total
      radiosulfate incorporation into proteoglycans which was mainly found in the
      cell/matrix rather than in the media-associated compartment. There were also
      differences in the proteoglycan synthesis patterns of astrocyte cultures isolated
      from these CNS regions. These findings suggest that (1) astrocytes are regionally
      heterogenous in their reactive response to beta AP and (2) that specific
      molecules, in addition to beta AP, may exist following trauma or disease which
      trigger reactive states in astroglia in the cerebellum or spinal cord. These
      local differences in the interaction between beta AP and surrounding astrocytes
      may play a role in the region-specific pathogenesis of Alzheimer's disease.

PMID- 7821398
TI  - Apoptotic mechanisms in targeted neuronal cell death by chromophore-activated
      photolysis.
AB  - Apoptosis influences early development and later refinement in adult tissues.
      Experiments in which embryonic neurons or multipotent neural precursor cells are
      transplanted into regions of neuronal degeneration following targeted photolytic
      cell death show similar regulation of neuronal migration and differentiation. In
      those experiments, transplanted cells sought to restore normal cytoarchitecture
      by preferential migration into neuron deficient regions, assumption of pyramidal
      morphology, and early process elongation. Control transplants into intact and
      kainic acid lesioned cortex failed to elicit similar responses. We investigated
      the possibility that mechanisms of neuronal death common to apoptosis and
      targeted photolysis could explain the similar developmental influences. We
      assessed the pathways of cellular injury and eventual cell death in neuroblastoma
      and PC12 cell cultures labeled with nanospheres carrying the chromophore NH4
      chlorin e6 and subjected to photoactivation (1) pharmacologically by scavengers
      of singlet oxygen and inhibitors of lysosomal proteases, (2) histologically by
      electron, fluorescence, and light microscopy, and (3) biochemically with binding
      of cellular DNA by propridium iodide, 3'-OH DNA end terminal labeling, and gel
      electrophoresis. We found that nanospheres were incorporated into lysosomes, and
      exposure to light energy led to singlet oxygen (1O2) production and cell death
      within both neuroblastoma and PC-12 cell lines. Scavengers of 1O2 prevented cell
      toxicity, while inactivation of lysosomal proteases reduced cell death.
      Morphologically, degenerating cells revealed release of proteases from lysosomes
      and disruption of cytoskeletal proteins. Apoptotic characteristics including
      early loss of cell adhesion, plasma membrane blebbing, and nuclear condensation
      and convolution were observed. Biochemically, DNA fragmentation was present in
      cells stained with propridium iodide and observed by 3'-OH end terminal labeling
      and gel electrophoresis. Thus, cells targeted by photolytically generated 1O2
      undergo a form of cell autolysis whose final common pathway is apoptotic. The
      slow, nonnecrotic process of targeted neuronal cell death in vivo may activate
      many of the same physiological cues activated by programmed cell death during
      normal development and during organizational refinement in the adult vertebrate
      nervous system. This may potentially explain the migration and differentiation of
      neocortical neurons and neural precursors transplanted into these regions of
      neuronal degeneration.

PMID- 7821400
TI  - Theileria: improved species discrimination using oligonucleotides derived from
      large subunit ribosomal RNA sequences.
AB  - Partial nucleotide sequences of large subunit ribosomal RNA (LSU rRNA) coding
      genes of Theileria parva and T. taurotragi were determined. Alignment of the T.
      parva and T. taurotragi sequences revealed species-specific regions within the
      LSU rRNA genes. A major species-variable region, located between the first and
      second conserved secondary structure domains of LSU rRNA, was identified. The
      sequence of the major species-variable region was determined for T. annulata, T.
      buffeli, and an unclassified Theileria species isolated from buffalo. Species
      specific oligonucleotides complementary to LSU rRNA sequences were designed for
      five species of Theileria. The oligonucleotide probes discriminated between
      Theileria species when hybridized to amplified parasite LSU rRNA genes or
      directly to parasite rRNA. Three species-specific oligonucleotides derived from
      nonoverlapping sequences were developed for each of T. parva and T. taurotragi. A
      simplified procedure was developed in which T. parva- and T. taurotragi-specific
      oligonucleotides were used to discriminate the two species under nonstringent
      hybridization and washing conditions. Use of the nonstringent conditions also
      increased the sensitivity of target detection. Comparison of Theileria species
      specific oligonucleotides derived from large subunit and small subunit rRNA genes
      demonstrated that, for closely related species, probes derived from LSU rRNA
      sequences had improved specificity.

PMID- 7821399
TI  - Morphine inhibits Purkinje cell survival and dendritic differentiation in
      organotypic cultures of the mouse cerebellum.
AB  - The effects of morphine on the morphogenesis and survival of calbindin-D28k
      immunoreactive Purkinje cells were studied in organotypic explant cultures
      isolated from 1- or 7-day-old mouse cerebella. To reduce experimental
      variability, bilaterally matched pairs of organotypic cultures were used to
      compare the effects of opiate drug treatment. One explant within each pair was
      untreated, while the remaining explant was continuously treated for 7 to 10 days
      with morphine, morphine plus naloxone, or naloxone alone. In explants derived
      from 1-day-old mice, morphine treatment significantly reduced Purkinje cell
      dendritic length compared to symmetrically matched untreated control explants.
      The concentration of morphine estimated to cause a half-maximal reduction (EC50)
      in dendritic length was 4.9 x 10(-8) M. At higher concentrations (EC50 = 3.6 x
      10(-6) M), morphine also significantly decreased the number of Purkinje cells in
      explants from 1-day-old mice compared to untreated explants. Electron microscopy
      identified increased numbers of degenerating Purkinje cells in explants derived
      from 1-day-old mice. This showed that high concentrations (10(-5) M) of morphine
      reduced Purkinje cell numbers by decreasing their rate of survival. In explants
      derived from 7-day-old mice, morphine (10(-5) M) neither affected Purkinje cell
      dendritic length nor cell numbers compared to symmetrically matched untreated
      (control) explants. Collectively, these findings suggest that morphine per se,
      through a direct action on the cerebellum, can affect Purkinje cell
      differentiation and survival. The results additionally suggest that there is a
      critical period during development when Purkinje cells are especially vulnerable
      to the effects of morphine.

PMID- 7821401
TI  - Amino acid exchange activity of the alanine transporter of Giardia intestinalis.
AB  - The influx and efflux of alanine and other amino acids was studied in
      trophozoites of Giardia intestinalis. Transport of L-[2,3-3H]alanine was used as
      the index of influx. On the basis of the competition of L-[2,3-3H]alanine uptake
      by analogues of alanine, the substrate specificity of the alanine transporter was
      determined. The transporter is an antiport. Influx of alanine or those analogues
      which inhibited alanine influx caused the efflux of intracellular alanine and a
      number of amino acids structurally related to alanine. Amino acids unrelated to
      alanine, such as glutamate, effluxed at a slow rate, and the efflux was not
      stimulated by extracellular alanine or alanine analogues. However, there was a
      subset of intracellular amino acids, the alanine subset comprising alanine,
      serine, glycine, and threonine, the efflux of which was stimulated by external
      alanine or alanine analogues. Direct measurement by amino acid analysis
      demonstrated intracellular accumulation of alanine analogues concomitant with the
      efflux of the alanine subset. These data indicate unequivocal evidence of
      exchange of intracellular alanine with extracellular alanine analogues, with a
      1:1 molar stoichiometry. This is the first demonstration in G. intestinalis of
      the antiport function of an amino acid transporter.

PMID- 7821402
TI  - Giardia lamblia: in vitro cytopathic effect of human isolates.
AB  - The variable clinical course of human giardiasis may be due in part to
      differences in the virulence of various strains of Giardia lamblia. To address
      this issue, the in vitro cytopathic effect of isolates obtained from human
      symptomatic or asymptomatic infections was assessed by ultrastructural and
      electrophysiological methods. Axenic trophozoites of 10 strains of G. lamblia
      isolated from children with infections in Mexico City were cultured for 12 to 24
      hr on live MDCK epithelial cells. No decrease in transepithelial resistance of
      MDCK monolayers mounted in Ussing chambers was detected with any of the isolates
      analyzed. On the contrary, trophozoites or media in which the isolates grew
      produced up to a twofold increase in transepithelial resistance. Transmission and
      scanning electron microscopy revealed that all isolates of G. lamblia,
      irrespective of their origin, gave rise to focal regions of microvilli depletion.
      These modifications were induced by the close attachment of the ventrolateral
      flange of the parasite adhesive disk to the apical surface of MDCK cells. The
      circular imprints evolved progressively to larger areas devoid of microvilli. In
      conclusion, under in vitro conditions, isolates of G. lamblia trophozoites
      derived from symptomatic or asymptomatic human infections damage epithelial
      cultured cells mainly by depleting their microvilli. None of the isolates showed
      evidence of an invasive effect.

PMID- 7821403
TI  - Schistosoma mansoni: interleukin-1 increases phagocytosis and superoxide
      production by hemocytes and decreases output of cercariae in schistosome
      susceptible Biomphalaria glabrata.
AB  - Decreases in the number of Schistosoma mansoni cercariae released from
      susceptible M-line Biomphalaria glabrata were detected following injection with
      the recombinant human cytokine, interleukin-1. No differences in either the time
      post-exposure at which shedding began or the percentage of snails shedding
      cercariae were detected between interleukin-1 injected, heat-inactivated
      interleukin-1 injected, or sham injected controls. However, sham injected and
      heat-inactivated interleukin-1 injected snails maintained significantly higher
      (approximately three-fold) levels of cercarial production compared to interleukin
      1 injected snails over 8 weeks of cercarial shedding. Injection of interleukin-1
      into schistosome-susceptible (M-line) and resistant (13-16-R1) strains of B.
      glabrata increased hemocyte phagocytosis of target particles and phagocytosis
      stimulated O2- production in both snail strains at 24 hr postexposure to the
      parasite. Resistant 13-16-R1 snails maintained, on average, 2.4 times the number
      of O2- producing phagocytic cells than did M-line susceptible snails, indicating
      that the incomplete abrogation of cercarial shedding in M-line snails may be due
      to an inadequate number of activated circulating effector cells in these snails.
      These data strongly support the contention that the evolutionarily conserved
      cytokine, interleukin-1, or a molecule in snail plasma with interleukin-1-like
      immunospecificity, biological activity, and function plays a significant role in
      the maintenance of susceptibility or resistance to S. mansoni infection in B.
      glabrata. Finally, these data also supply evidence for the evolutionary
      conservation of the function and role of interleukin-1, O2-, and antioxidant
      defense mechanisms in this host-parasite relationship.

PMID- 7821404
TI  - Schistosoma mansoni: interaction of nuclear extracts with the CCAAT-binding site
      revealed by the gel shift assay.
AB  - Analysis of the 5'-flanking region of the gene encoding the 28-kDa glutathione S
      transferase of Schistosoma mansoni (Sm28GST) indicated the presence of motifs
      identical to AP-1 and CCAAT-family transcription factor recognition sequences.
      Gel retardation experiments showed that nuclear extracts from adult S. mansoni
      bound to an oligodeoxynucleotide containing at CCAAT box. A DNA fragment
      corresponding to the region of Sm28GST containing the CCAAT motif was
      demonstrated to interact with schistosome nuclear proteins. This binding was
      dependent on the presence of the CCAAT pentanucleotide motif. Nuclear factor Y
      (NF-Y) is a member of the CCAAT transcription factor family that has absolute
      requirement for the CCAAT sequence and that is highly conserved throughout
      evolution. The results of a PCR-based strategy aimed at cloning the NF-YA protein
      of S. mansoni are presented.

PMID- 7821405
TI  - Schistosoma mansoni: characterization of the gene encoding Sm23, an integral
      membrane protein.

PMID- 7821406
TI  - The hsp83 intergenic region in Leishmania: conservation of sequence and function
      across two species.

PMID- 7821407
TI  - A rapid technique for the detection of DNA polymorphisms in Plasmodium.

PMID- 7821408
TI  - Schistosoma mansoni: characterization of excretory-secretory polypeptides
      synthesized in vitro by daughter sporocysts.
AB  - Excretory-secretory (ES) products of daughter sporocysts have been implicated in
      the modulation of snail host reproductive physiology. Because of the potentially
      important role of ES products in snail reproduction, newly synthesized ES
      polypeptides of in vitro-cultured Schistosoma mansoni daughter sporocysts were
      examined in pulse-chase studies using [35S]methionine followed by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), fluorography, and scanning
      densitometry. Fluorograms of SDS-PAGE-separated ES proteins revealed that
      sporocysts released a wide variety of polypeptides ranging in molecular weight
      from 17 to 200 kDa into supernatants during 6 days of in vitro culture at 26
      degrees C. Moreover, the general pattern of synthesis and release of daughter
      sporocyst polypeptides into culture supernatants differed from those ES
      components previously described from primary or mother sporocysts. Although
      quantitative densitometry revealed that total labeled ES protein released into
      culture supernatants was consistent for all three pulse-chase periods, there were
      significant differences in the quantities of individual polypeptide peaks. The
      dynamics of the synthesis and release of eight polypeptides chosen for further
      analysis varied over time. Several ES polypeptides (110, 95, and 25 kDa) were
      released in relatively constant amounts, while some (69 and 44 kDa) increased and
      others (38 and 35 kDa) decreased in quantity over the same period of culture. It
      is hypothesized that the 38- and 35-kDa polypeptides may be important candidate
      inhibitory molecules because of the correlation between their early release into
      culture supernatants and the inhibitory effect of Day 1-2 daughter sporocyst ES
      products on polysaccharide synthesis in the albumen gland of the snail
      host.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7821410
TI  - Toxoplasma gondii: stable complementation of sag1 (p30) mutants using SAG1
      transfection and fluorescence-activated cell sorting.
AB  - Toxoplasma gondii and the related Apicomplexan protozoan pathogens, Plasmodium,
      Cryptosporidium, and Eimeria, are obligate intracellular parasites which cause
      severe disease in their hosts. The recent development of transient transfection
      of Toxoplasma permits the development of strategies utilizing "reverse genetics"
      to identify molecules critical to parasite survival within the host. We have
      utilized transfection of Toxoplasma tachyzoites to stably complement a sag1 (or
      p30) mutant that does not make detectable SAG1. Transfection of mutants with the
      wild-type SAG1 gene resulted in transient expression of SAG1 in approximately 15
      20% of the transfected population. Stable transformants were enriched by repeated
      sorting of live parasites using a fluorescein-labeled monoclonal antibody
      specific for SAG1. Cloned recombinant parasites expressed SAG1 at wild-type
      levels and maintained expression for over 5 months after transfection
      (approximately 300 divisions). Cloned transformants (which proved to be siblings)
      carried both the mutated gene and one copy of the transfected gene which had
      inserted randomly into the Toxoplasma genome.

PMID- 7821409
TI  - Schistosoma mansoni hexokinase: cDNA cloning and immunogenicity studies.
AB  - DNA encoding a Schistosoma mansoni hexokinase (SHEX) was amplified from cDNA by
      the polymerase chain reaction using opposing oligonucleotide primers designed to
      hybridize with two short segments of hexokinase coding sequences that are well
      conserved through evolution. The resulting DNA fragment was then used as a probe
      to identify a full-length hexokinase cDNA clone. SHEX cDNA encodes a 50-kDa
      protein that is approximately 46% homologous to rat hexokinase, 40% to rat
      glucokinase, and 34% to yeast hexokinase A. SHEX coding DNA was expressed within
      Escherichia coli cells and the 50-kDa recombinant product (rSHEX) was partially
      purified. Mice repeatedly immunized with rSHEX produced antibodies which
      recognize rSHEX but this offered no significant protection against subsequent
      cercarial challenge. On Western blots, rSHEX is weakly recognized by antisera
      against rat brain hexokinase but not by sera from three strains of mice
      experimentally infected with S. mansoni parasites or from numerous human
      schistosomiasis patients. Thus, unlike other reported S. mansoni glycolytic
      enzymes, hexokinase appears to be poorly immunogenic during schistosome infection
      and of limited potential as a vaccine candidate.

PMID- 7821411
TI  - Plasmodium falciparum: role of activated blood monocytes in erythrocyte membrane
      damage and red cell loss during malaria.
AB  - The role of Plasmodium falciparum and blood monocytes in the erythrocyte damage
      and pathogenesis of anemia has been investigated using two strains of the
      parasite; one laboratory-established strain (FSJ-M) and one wild, fresh, clinical
      isolate (PfPGI). Peripheral blood monocyte-induced growth inhibition of the
      parasites, erythrocyte membrane lipid peroxidation as seen by the formation of
      lipid peroxide products, and sensitivity to peroxide hemolysis at atmospheric
      oxygen were evaluated. The growth inhibition of FSJ-M by activated blood
      monocytes was greater than that of PfPGI. The extent of lipid peroxidation and
      sensitivity to hemolysis increased significantly as the parasites matured. These
      adverse effects were more marked following exposure to activated monocytes,
      especially in synchronized, parasitized RBCs. In addition, uninfected
      erythrocytes within the PfPGI parasite culture revealed a significant increase in
      the lipid peroxide formation (P < 0.01) and susceptibility to lysis (P < 0.05)
      under similar oxidant stress induced by monocytes from normal healthy donors.
      Furthermore, there was a direct correlation between membrane lipid peroxidation
      and peroxide hemolysis, both before and after monocyte exposure, suggesting a
      primary role of membrane peroxidation in red cell lysis. The contribution of
      intraerythrocytic parasites and nonspecific activation of blood monocytes in the
      pathophysiology of erythrocyte damage and anemia of P. falciparum infection is
      discussed.

PMID- 7821412
TI  - Brugia pahangi: differential granulomatous reactivity of infected jirds (Meriones
      unguiculatus) to fractions of adult worm extract.
AB  - Soluble extracts of adult Brugia pahangi (SSE) were fractionated by lectin
      affinity chromatography, followed by reversed phase HPLC. The immunologic and in
      vivo inflammatory reactivity of the resulting fractions were compared in jirds
      with acute and chronic infections of B. pahangi. When separated by SDS-PAGE, all
      fractions possessed bands which were recognized in Western blots by antibodies
      from jirds with both acute and chronic infections. Fractions were coupled to
      sized Sepharose beads that were subsequently embolized into the lungs of infected
      and uninfected control jirds. Granulomas were induced by SSE, the lectin column
      eluate, and HPLC fractions E, F, and G in acutely infected jirds. These reactions
      were significantly reduced in chronically infected jirds. HPLC fractions B, C,
      and D did not elicit an in vivo inflammatory response. A perivascular infiltrate
      of eosinophils and mononuclear cells was also observed in lungs of acutely
      infected jirds which received granuloma-inducing coated beads but not in lungs of
      similar jirds which received beads that did not induce this inflammatory
      response. Proliferative responses of splenocytes stimulated with SSE or the
      lectin eluate and lymph node cells and splenocytes stimulated with HPLC fractions
      B, C, or D corresponded to the in vivo granulomatous response to homologously
      coated beads. Correlations between in vivo inflammatory responses and in vitro
      proliferative responses were not seen using other fractions in these assays.
      These data indicate that varying degrees of granulomatous inflammation are
      induced by different filarial proteins mixtures and that the in vivo granuloma
      induction by antigen-coated beads will be useful in the identification of
      specific proteins involved in the induction, maintenance, and regulation of
      filariae-elicited inflammatory reactions. Although the size of these granulomas
      corresponds to severity of granulomatous inflammatory responses visualized within
      the jird lymphatics during the course of infection, the reaction does not
      correlate in all instances to lymphoproliferative responses of cells from
      peripheral lymph nodes or the spleen. Distinct differences between antibody and
      granulomatous reactivity to some fractions were noted.

PMID- 7821413
TI  - Babesia bigemina: host factors affecting the invasion of erythrocytes.
AB  - Babesia bigemina merozoites enter their host's erythrocytes by an unknown
      mechanism that likely involves parasite surface components. Identification of the
      parasite ligands involved in invasion is hampered by a lack of basic information
      about the invasion characteristics of Babesia bigemina. Therefore, restrictions
      on the species of red blood cells (RBC) that are susceptible to invasion were
      examined as well as the roles of erythrocyte ligands. An invasion assay and a
      proliferation assay were developed for this study. Unlike some other species of
      Babesia that infect cattle, B. bigemina failed to enter RBC from most animals
      that are not natural hosts, suggesting that a species restricted receptor
      mechanism mediates invasion. Two carbohydrates which are prominent on the surface
      of bovine erythrocytes, N-acetylglucosamine and N-acetylgalactosamine, when added
      to cultures, reduced the ability of B. bigemina merozoites to invade
      erythrocytes. Neuraminidase or trypsin treatment of bovine erythrocytes
      significantly decreased their susceptibility to invasion whereas chymotrypsin had
      little effect. These data imply that proteinaceous erythrocyte ligands and
      carbohydrate residues may be involved in the invasion process. Identification of
      a species-specific pattern of invasion and RBC treatments that render cells
      refractory to invasion may provide the basis for the characterization of B.
      bigemina erythrocyte binding molecules based on their differential binding to
      invasion competent and refractory cells.

PMID- 7821414
TI  - Leishmania donovani: enhanced expression of soluble acid phosphatase in the
      presence of sinefungin, an antiparasitic agent.
AB  - Sinefungin, an antileishmanial nucleoside, induces morphological and
      ultrastructural changes in promastigotes of Leishmania donovani. The most
      important modifications are the enlargement of the flagellar pocket and the
      increased activity of the Golgi apparatus. Cytoenzymatic labeling demonstrates an
      increased activity of the soluble acid phosphatase in the flagellar reservoir of
      sinefungin-treated cells. The affinity constant remained unchanged. Analyzes by
      Western blot demonstrate an increased amount of the enzyme in the treated cells.
      The increased amount was not due to impaired enzyme release, as in the external
      medium the acid phosphatase was also enhanced but to a lesser extent. Under
      identical conditions the membrane-bound acid phosphatase was not modified. These
      results indicate that the enlargement of the flagellar pocket is the consequence
      of the accumulation of acid phosphatase and other Golgi-mediated enzyme provoking
      unbalanced cytoplasmic exchange. Sinefungin has the same effects on Leishmania
      tropica promastigotes. However, these effects are not specific to sinefungin.
      Another molecule, taxol, also induced cell rounding accompanied by increased acid
      phosphatase activity. Under conditions where cell rounding is not observed, in
      stationary phase or with compounds which stopped proliferation without shape
      change, no increase in the amount of acid phosphatase could be observed. These
      results clearly demonstrate a correlation between morphological, ultrastructural
      changes and the stimulated expression of acid phosphatase.

PMID- 7821415
TI  - Ascaris suum: characterization of transmural and hypodermal potentials.
AB  - Electrophysiological measurements demonstrate that an electrochemical potential
      exists across the body wall of parasitic nematodes. The ionic dependence of this
      transmural electrical potential (Etm) in the gastrointestinal nematode Ascaris
      suum was investigated using conventional electrophysiological techniques. Etm
      recorded from intact A. suum maintained in artificial pseudocoelomic fluid (APF)
      was -40 +/- 12 mV. This potential was more sensitive to external acetate than to
      Na+, K+, or Cl-, although elimination of most Na+ from the medium significantly
      hyperpolarized the body wall. An Ussing chamber and isolated segments of A. suum
      body wall were used to delineate the barrier characteristics of the individual
      components of the body wall: the cuticle and the inward- and outward-facing
      membranes of the hypodermis. The cuticle (i.e., muscle and hypodermis scraped
      away) is highly permeable to both inorganic and organic ions, with the rank-order
      of permeability among ions tested being K+ > Na+ = Cl- > acetate- > gluconate-.
      The inward- and outward-facing membranes of the hypodermis were more polarized
      than the body wall complex, exhibiting potentials in APF of -47.6 +/- 6 mV (Ei)
      and -74.9 +/- 7 mV (Eo) versus -26 +/- 8 mV (Etm for isolated body wall
      segments), respectively. The electrical potential across the hypodermal membranes
      became depolarized when high K+ medium or low acetate medium was added to the
      muscle side, but not when added to the cuticle side of isolated body wall
      segments. Etm, Eo, and Ei were unaffected by reduction of Na+, K+, or Cl-
      concentrations in the recording medium. All three potentials, however, became
      markedly depolarized when the temperature of the incubation medium was reduced.
      These results indicate that the cuticle/hypodermis complex of A. suum is
      differentially permeable to both inorganic and organic ions and suggest that
      active transport of ions or outward diffusion of metabolic end-products
      contributes extensively to the maintenance of transmural electrochemical
      gradients.

PMID- 7821416
TI  - Crithidia fasciculata as feeder cells for malaria parasites.
AB  - Crithidia fasciculata was used to replace murine peritoneal wash cells as feeder
      cells for the adaptation of Plasmodium falciparum isolates to continuous culture
      in vitro, thus avoiding the need to sacrifice animals. Fourteen of 17 malaria
      parasite isolates in one study, and 12 of 12 isolates in a second study, were
      successfully adapted to continuous culture in the presence of C. fasciculata,
      while only 5 of 17 parallel control isolates in the first study, and 2 of 12
      isolates in the second study, were adapted in the absence of any feeder cells.
      Biochemical assays were performed to investigate various hypotheses put forward
      to explain the mode of action of feeder cells. No effect of C. fasciculata feeder
      cells was observed on lactate removal, osmotic pressure, or glucose or amino acid
      content of the malaria culture media. This feeder cell system was shown to reduce
      the pH of the malaria culture medium. Neither this feeder system nor another
      system, murine peritoneal macrophages, had any effect on the cysteine content of
      the culture medium. C. fasciculata was shown to reduce the redox potential of the
      culture medium, as were other malaria growth enhancers including cysteine and
      glutathione. This effect on the redox potential of the culture medium is proposed
      to be a possible mode of action for the feeder cell systems studied.

PMID- 7821417
TI  - Persistent oxidative stress in cancer.
AB  - DNA of cancers such as renal cell carcinoma and mammary invasive ductal
      carcinoma, is persistently exposed to more oxidative stress than that of adjacent
      normal tissue. We suggest that the concept of 'persistent oxidative stress in
      cancer' may open up a new research area, explaining part of the characteristic
      tumor biology of cancer such as activated transcription factors and proto
      oncogenes, genomic instability, chemotherapy-resistance, invasion and metastasis.

PMID- 7821418
TI  - A catalytic subunit of calpain possesses full proteolytic activity.
AB  - Previous studies on the refolding of calpain, a heterodimer comprising a
      catalytic 80 kDa subunit and a regulatory 30 kDa subunit, indicate that both
      subunits are required for the expression of full protease activity. We reexamined
      the conditions for refolding of calpain and found that under optimized conditions
      the renatured 80 kDa subunit has full enzyme activity even in the absence of the
      30 kDa subunit. The 30 kDa subunit stabilizes the 80 kDa subunit rather than
      enhancing its activity. The theory that calpain functions as a dimer requires
      reexamination.

PMID- 7821419
TI  - The immediate vicinity of mouse metallothionein-I gene contains two sites
      conferring glucocorticoid inducibility to the heterologous promoter.

PMID- 7821420
TI  - Alternating purine-pyrimidine tract activates transcription from the Rouse
      sarcoma virus LTR lacking promoter and enhancer elements.
AB  - The transcriptional control region of the Rouse sarcoma virus long terminal
      repeats (LTR) was shown to contain enhancer and promoter elements located within
      200 base pairs upstream from the transcription initiation site [Cullen et al.
      (1985) Mol. Cell. Biol. 5, 438-447]. Deletion of these elements results in
      significant loss of LTR transcriptional activity. In the present paper it is
      shown that a short alternating purine-pyrimidine sequence can restore the
      constitutive activity of the Rouse sarcoma virus LTR in the absence of upstream
      elements when inserted in close proximity to the transcription initiator site.
      The possible molecular bases of this phenomena are discussed.

PMID- 7821421
TI  - Temperature-induced micellar-lamellar transformation in binary mixtures of
      saturated phosphatidylcholines with sodium cholate.
AB  - The transition states of binary mixtures of dipalmitoyl- and
      dimyristoylphosphatidylcholines with sodium cholate at the reversible temperature
      induced micellar-lamellar transformation were characterized by turbidimetry,
      electron microscopy, 31P NMR and differential scanning calorimetry. This
      transformation is triggered by the phospholipid acyl chain melting, and appears
      to include two structural pathways: (i) from discoidal mixed micelles to network
      like structures composed of long interlaced rod-like micelles, then to multilayer
      membrane structures, and finally to multilamellar vesicles; and (ii) from
      discoidal micelles to membrane fragments and finally to unilamellar vesicles.

PMID- 7821422
TI  - A novel pancreatic beta-cell isoform of calcium/calmodulin-dependent protein
      kinase II (beta 3 isoform) contains a proline-rich tandem repeat in the
      association domain.
AB  - There is evidence for a role for calcium/calmodulin-dependent protein
      phosphorylation in regulation of insulin secretion but the molecular nature of
      the kinase(s) responsible is unknown. In this study, the screening of a neonatal
      rat islet cDNA library resulted in the isolation of a 2 kb clone that was 99%
      homologous to the beta' isoform of calcium/calmodulin-dependent protein kinase
      II. The predicted 589 amino acid sequence with a calculated mass of 64,976 Da
      contained a 24 amino acid deletion in addition to the 15 amino acid deletion that
      differentiates the beta' from the beta isoform, and included an 86 amino acid
      novel domain consisting of a tandem repeat of proline-rich residues. The
      expression of this new isoform of calcium/calmodulin-dependent protein kinase II
      (beta 3) was confirmed in beta-cell lines and testis by DNA amplification of the
      sequence encoding the inserted domain by reverse transcriptase-polymerase chain
      reaction, followed by Southern analysis.

PMID- 7821423
TI  - An A-form of poly[d(A-C)].poly[d(G-T)] induced by mercury (II) as studied by UV
      and FTIR spectroscopies.
AB  - The conformational changes of poly[d(A-C)].poly[d(G-T)] induced by Hg(ClO4)2 in
      aqueous solution have been studied using UV absorption and fourth derivative
      spectrophotometries, and FTIR spectroscopy. The UV absorption and fourth
      derivative spectra reflect changes in the polynucleotide stacking interactions as
      a result of the metal-polynucleotide interaction. The fourth derivative spectra
      do not indicate a Z-form either at low or at high metal-to-polynucleotide ratios.
      Furthermore, the infrared spectrum at high metal-to-polynucleotide ratio (r =
      1.2; r = [Hg(ClO4])2/[nucleotide] molar ratio) has the main features of an A
      form, in contrast with previous CD studies which proposed that the polynucleotide
      adopts a Z-form under these conditions. The nature of a different conformation of
      the polynucleotide induced at low r-ratios (r < or = 0.2) is discussed.

PMID- 7821424
TI  - The 'CheA' and 'CheY' domains of Myxococcus xanthus FrzE function independently
      in vitro as an autokinase and a phosphate acceptor, respectively.
AB  - FrzE is a chemotaxis protein in Myxococcus xanthus which has sequence homology to
      two different chemotaxis proteins of enteric bacteria, CheA (autokinase) and CheY
      (phosphate acceptor) [Proc. Natl. Acad. Sci. USA 87 (1990) 5898-5902]. It was
      also shown that a recombinant FrzE protein was autophosphorylated when incubated
      in the presence of ATP and Mn2+ [J. Bacteriol. 172 (1990) 6661-6668]. In this
      study, we further investigated the biochemical properties of FrzE. Two
      recombinant proteins were produced: one containing only the 'CheA' domain of FrzE
      and the second only the 'CheY' domain. The CheA domain polypeptide contained the
      autokinase activity which was absent from the CheY domain polypeptide. The
      phosphorylated CheA domain polypeptide as well as the intact FrzE protein were
      able to transfer phosphate groups to the CheY domain peptide. These results
      indicate that FrzE has structural as well as functional homologies to CheA and
      CheY in a single polypeptide.

PMID- 7821425
TI  - Chloroplast import and sequential maturation of pea carbonic anhydrase: the roles
      of various parts of the transit peptide.
AB  - Chloroplast pea carbonic anhydrase is synthesised in the cytosol with an
      unusually long bipartite N-terminal extension of the mature sequence previously
      proposed to serve as a transit peptide. Studies of import into pea chloroplasts
      show that the N-terminal 69 amino acids of the previously proposed transit
      peptide is sufficient for translocation and localisation to the stroma, while the
      acidic C-terminal part does not seem to have any function in these processes.
      Processing of the in vitro imported precursors is shown to be at a new cleavage
      site located in the middle of the actual transit peptide. The results indicate
      that maturation occurs in more than one step. The time-course does not seem to be
      dependent on the age of the chloroplast but on the age of the translocated
      precursor.

PMID- 7821426
TI  - Modulation of GSK-3-catalyzed phosphorylation of microtubule-associated protein
      tau by non-proline-dependent protein kinases.
AB  - The phosphorylation of bovine tau, either by GSK-3 alone or by a combination of
      GSK-3 and several non-proline-dependent protein kinases (non-PDPKs), was studied.
      GSK-3 alone catalyzed the incorporation of approximately 3 mol 32P/mol tau at a
      relatively slow rate. Prephosphorylation of tau by A-kinase, C-kinase, or CK-2
      (but not by CK-1, CaM kinase II or Gr kinase) increased both the rate and extent
      of a subsequent phosphorylation catalyzed by GSK-3 by several-fold. These results
      suggest that the phosphorylation of tau by PDPKs such as GSK-3 (and possibly MAP
      kinase, cdk5) may be positively modulated at the substrate level by non-PDPK
      catalyzed phosphorylations.

PMID- 7821427
TI  - Cysteine biosynthesis in plants: isolation and functional identification of a
      cDNA encoding a serine acetyltransferase from Arabidopsis thaliana.
AB  - A cDNA encoding for serine acetyltransferase which catalyzes the committing step
      of cysteine biosynthesis has been cloned from Arabidopsis thaliana. The plant
      protein has a predicted molecular weight of 32.8 kDa and shows up to 43% of amino
      acid homology to bacterial serine acetyltransferases. It complements a serine
      acetyltransferase negative E. coli mutant and can be enzymatically determined in
      the heterologous host. The corresponding mRNA is predominantly expressed in light
      exposed tissue and represents one of at least two related genes.

PMID- 7821428
TI  - Detection of tryptase TL2 and CD26 antigen in brain-derived cells non-permissive
      to T-cell line-tropic human immunodeficiency virus type 1.
AB  - Tryptase TL2 purified from MOLT-4 human T cells binds to the envelope protein of
      human immunodeficiency virus type 1 (HIV-1). Tryptase TL2 and CD26 antigen are
      supposed to play roles in HIV-1 entry into cells. Although CD4 is a principal
      receptor for HIV-1, brain cells expressing the CD4 antigen are not permissive to
      HIV-1 strains infectious to monocyte or T-cell lines. We examined whether the non
      permissiveness of the brain-derived cells to standard HIV-1 strains could be
      explained by a lack of tryptase TL2 or CD26. Western blots showed that the
      amounts of tryptase TL2 expressed in cell lysates prepared from the brain-derived
      cells were similar to those prepared from various cells susceptible to HIV-1
      strains. Furthermore, flow cytometry revealed the presence of the CD26 antigen on
      the cell surface of many types of cells. The resistance of the brain-derived
      cells to standard HIV-1 strains is not due to a lack of tryptase TL2 or CD26.

PMID- 7821429
TI  - Active site titration of bovine beta-trypsin by N alpha-(N,N-dimethylcarbamoyl)
      alpha-aza-lysine p-nitrophenyl ester: kinetic and crystallographic analysis.
AB  - Kinetics of bovine beta-trypsin (trypsin) with the N alpha-(N,N
      dimethylcarbamoyl)-alpha-aza-lysine p-nitrophenyl ester (Dmc-azaLys-ONp) was
      obtained at pH 6.2 and 21.0 degrees C. Dmc-azaLys-ONp shows the characteristics
      of an optimal active site titrant in that it (i) gives titrations in a short
      time, (ii) is a stable and soluble compound with a stoichiometric reaction that
      is easily and directly detectable, and (iii) allows titrations over a wide range
      of enzyme concentration. Moreover, the three-dimensional structure of the
      trypsin.N alpha-(N,N-dimet hylcarbamoyl)-alpha-aza-lysine acyl.enzyme adduct has
      been solved by X-ray crystallography at 2.0 A resolution (R = 0.145). The Dmc
      azaLys moiety of the active site titrant is sited in the serine proteinase
      reaction center, and is covalently linked to the OG atom of the Ser195 catalytic
      residue.

PMID- 7821430
TI  - Refined structure for the complex of D-gluco-dihydroacarbose with glucoamylase
      from Aspergillus awamori var. X100 to 2.2 A resolution: dual conformations for
      extended inhibitors bound to the active site of glucoamylase.
AB  - The crystal structure at pH 4 of the complex of glucoamylase II(471) from
      Aspergillus awamori var. X100 with the pseudotetrasaccharide D-gluco
      dihydroacarbose has been refined to an R-factor of 0.125 against data to 2.2 A
      resolution. The first two residues of the inhibitor bind at a position nearly
      identical to those of the closely related inhibitor acarbose in its complex with
      glucoamylase at pH 6. However, the electron density bifurcates beyond the second
      residue of the D-gluco-dihydroacarbose molecule, placing the third and fourth
      residues together at two positions in the active site. The position of relatively
      low density (estimated occupancy of 35%) corresponds to the location of the third
      and fourth residues of acarbose in its complex with glucoamylase at pH 6. The
      position of high density (65% occupancy) corresponds to a new binding mode of an
      extended inhibitor to the active site of glucoamylase. Presented are possible
      causes for the binding of D-gluco-dihydroacarbose in two conformations at the
      active site of glucoamylase at pH 4.

PMID- 7821431
TI  - Structure and differential response to abscisic acid of two promoters for the
      cytosolic copper/zinc-superoxide dismutase genes, SodCc1 and SodCc2, in rice
      protoplasts.
AB  - We determined the 5'-flanking sequences of two nuclear genes (SodCc1 and SodCc2)
      encoding cytosolic copper/zinc-superoxide dismutase in rice (Oryza sativa L.).
      Utilizing transient beta-glucuronidase (GUS) reporter assays, functional promoter
      GUS analysis was performed in rice protoplasts exposed to the phytohormone
      abscisic acid (ABA) or the antioxidant sulfhydryl reagent, dithiothreitol (DTT).
      Transcriptional activities from both SodCc-GUS fusions were stimulated by DTT,
      which induces the promoter activity of the tobacco SodCc gene [Proc. Natl. Acad.
      Sci. USA 90 (1993) 3108-3112]. ABA had no effect on SodCcl-GUS expression but
      specifically induced the gene expression of the SodCc2-GUS fusion. The
      simultaneous application of ABA and gibberellin A3, however, abolished the
      enhancing effect of ABA. These results indicated that two rice SodCc promoters
      differentially respond to externally supplied ABA and that one of the regulatory
      factors for plant SodCc expression is ABA in addition to cellular redox
      modulating antioxidants.

PMID- 7821432
TI  - Molecular characterization and cell cycle-regulated expression of a cDNA clone
      from Arabidopsis thaliana homologous to the small subunit of ribonucleotide
      reductase.
AB  - A cDNA clone isolated from an Arabidopsis thaliana cell suspension library showed
      highly significant homology to the small subunit of ribonucleotide reductase (R2)
      from different species. The 340 amino acid-long deduced putative protein contains
      all the residues that are important for the enzyme activity and structure. In A.
      thaliana this enzyme is encoded by a single-copy gene. In synchronized tobacco
      BY2 cells the corresponding mRNAs specifically accumulate during the S phase of
      the cell cycle.

PMID- 7821433
TI  - Stoichiometry of the EF-Tu.GTP complex with aminoacyl-tRNA: ternary of
      quinternary?
AB  - The stoichiometry of the complex formed between the Escherichia coli polypeptide
      elongation factor EF-Tu, GTP and valyl-tRNA(val) has been determined by non
      enzymatic deacylation studies on mixtures of the components at well-defined
      concentrations. A titration end-point was found corresponding to a 1:1 complex of
      EF-Tu.GTP with the aminoacylated-tRNA i.e. formation of a ternary complex. The
      result conforms to the classical model of the elongation step and not to the
      revolutionary proposition of the formation of a 2:2:1 complex; quinternary
      complex (EF-Tu.GTP)2.aa-RNA.

PMID- 7821434
TI  - PMA-induced down-regulation of the receptor for alpha 2-macroglobulin in human
      U937 cells.
AB  - Transcription and expression of the urokinase (uPA) receptor (uPAR) are strongly
      stimulated by PMA. As for uPAR, the expression of alpha 2-MR is regulated by PMA
      in U937 cells. Ligand blotting experiments with the 39 kDa receptor-associated
      protein RAP, a ligand for alpha 2-MR, indicated that alpha 2-MR levels first
      increased and then decreased after PMA treatment. FACscan as well as
      immunoblotting analysis with alpha 2-MR-specific antibodies showed an identical
      trend: alpha 2-MR levels increased within the first day of treatment with PMA,
      decreased at later times, and totally disappeared by three days of treatment. The
      effect of PMA was not due to transcriptional down-regulation, as the alpha 2-MR
      mRNA level did not decrease at later times. Sensitivity of U937 cells to uPA
      saporin, a toxin conjugate that reguires binding to uPAR for killing activity,
      was also markedly decreased. These results suggest that uPAR-mediated endocytosis
      depends on alpha 2-MR expression.

PMID- 7821435
TI  - T cell receptor-mediated stimulation of mouse thymocytes induces up-regulation of
      the GM2/GD2 synthase gene.
AB  - cDNA clones of the mouse GM2/GD2 synthase (EC 2.4.1.92) gene were isolated, and
      their analyses revealed that the protein has a type II transmembrane structure
      with 533 amino acids, which was very similar to the human homolog except for the
      mRNA size. The mRNA level in thymocytes dramatically increased after treatment
      with anti-CD3 monoclonal antibody, whereas it was not elevated when treated with
      prostaglandin E2. In situ hybridization showed an elevation of mRNA levels in
      medullar thymocytes, suggesting that T cell receptor-mediated signaling induces
      up-regulation of the GM2/GD2 synthase gene in mature thymocytes.

PMID- 7821436
TI  - Prolactin induces growth inhibition and promotes differentiation of CHO cells
      stably transfected with prolactin receptor complementary DNA.
AB  - We have characterized a stable and functional transfectant of the rabbit
      prolactin receptor in Chinese hamster ovary cells, and investigated the action of
      prolactin (PRL) on the growth and differentiation of this transfectant (clone
      E32). PRL induced a significant inhibition of E32 cell proliferation. Growth
      inhibition correlated with gene induction of the molecular marker of ovarian
      differentiation cholesterol side chain cleavage P450 (P450scc). Both effects were
      inversely proportional to cell confluence. The limits and potential development
      of such transfected cellular systems are discussed.

PMID- 7821437
TI  - Human A-myb gene encodes a transcriptional activator containing the negative
      regulatory domains.
AB  - The myb gene family has three members, c-myb, A-myb, and B-myb. A-myb mRNA is
      mainly expressed in testis and peripheral blood leukocytes. A-Myb can activate
      transcription from the promoter containing Myb-binding sites in all cells
      examined. In addition to the two domains (a DNA-binding domain and a
      transcriptional activation domain), two negative regulatory domains have been
      identified in A-Myb. These results indicate that A-Myb functions as a
      transcriptional activator mainly in testis and peripheral blood cells, and the
      regulatory mechanism of A-Myb activity is similar to that of c-Myb.

PMID- 7821438
TI  - Photosensitive nitrile hydratase intrinsically possesses nitric oxide bound to
      the non-heme iron center: evidence by Fourier transform infrared spectroscopy.
AB  - Nitrile hydratase (NHase) from Rhodococcus sp. N-771 is a photosensitive enzyme
      that catalyzes hydration of nitriles to the corresponding amides. Light-induced
      Fourier transform infrared difference spectra between the inactive and active
      forms of NHase were measured with both the natural (14N) and 15N-labeled NHases.
      The results showed, for the first time, that NHase intrinsically possesses nitric
      oxide (NO) molecules bound to the non-heme iron center. The possible role of NO
      in the photoactivation process of NHase is discussed.

PMID- 7821439
TI  - delta-L-(alpha-aminoadipoyl)-L-cysteinyl-D-valine synthetase: the order of
      peptide bond formation and timing of the epimerisation reaction.
AB  - delta-L-(alpha-Aminoadipoyl)-L-cysteinyl-D-valine (ACV) synthetase catalyses the
      formation of the common precursor tripeptide of both the penicillin and
      cephalosporin antibiotics from the L-enantiomers of its constituent amino acids.
      Replacement of cysteine with L-O-methylserine in preparative-scale incubations
      led to the isolation of both L-O-methylserinyl-L-valine and L-O-methylserinyl-D
      valine dipeptides. The dipeptides were characterized with the aid of authentic
      synthetic standards by both 1H NMR and electrospray ionization MS. A revised
      mechanism for ACV biosynthesis involving formation of the cysteinyl-valine
      peptide bond before the epimerisation of valine and subsequent condensation with
      the delta-carboxyl of L-alpha-aminoadipate is therefore proposed.

PMID- 7821440
TI  - [Two dentistry-related specialties: forensic dentistry and oral genetics].

PMID- 7821441
TI  - [Posterior palatal sealing in Hungarian dental practice].
AB  - The purpose of the survey was to receive data about the methods, materials and
      instruments used in the development of the border seal at pharyngeal region. The
      problem concerned how the theoretical principles are realised in the everyday
      practice. A questionnaire consisting of 10 questions was given out to 35 dental
      laboratories in 31 towns of the country. 33 completed forms were returned. On the
      basis of the survey's results the authors conclude that in everyday practice
      practically nothing realizes from the recommendations of dental literature. The
      shape of the upper complete dentures' palatal seal is made by dental technicians,
      regretfully without the cooperation of dentists and what is more disappointing
      without their instructions. Dental technicians are left to their own resources to
      form the pharyngeal seal by mechanical engraving of the casts.

PMID- 7821442
TI  - [Microbiological study of the correlation between pontics and their mucosal and
      bone bases].
AB  - Authors investigated the possible relationship between different types of ponties
      and the development of dental plaque. Microbiological examinations revealed, that
      keeping to the strictest hygiene rules, even the least proposed saddle ponties
      should be omitted. Attention is called to the utmost importance of motivation and
      instruction in case of patients wearing bridges.

PMID- 7821443
TI  - [Laszlo Nemeth and dentistry].
AB  - Laszlo Nemet (1901-1975) was one of the most prominent representative of the XXth
      century's Hungarian literature. He has graduated as a medical doctor in 1925 and,
      between 1925-1929 when he was a novice writer--he was working as a dentist. He
      studied dentistry at the Department of Stomatology of the Holy Order of Charity's
      Hospital in Budapest. In his curriculum vitae he writes about the beginning of
      his private practice and its difficulties.

PMID- 7821444
TI  - [Anchoring of partial dentures using OT-CAP precision attachments].
AB  - The authors have examined a precision attachment recently invented in Hungary.
      They are reporting about the experience gained during clinical examination of
      dentures made in different classes on the basis of the Fabian and Fejerdy
      classification of partial edentulousness.

PMID- 7821445
TI  - [Measurement of the polished surface of upper and lower complete dentures].
AB  - The authors measured the polished surface of fifty upper and lower complete
      dentures, with regard to sex. The measurements were performed using a special
      computer assisted stereo-fotogrammetric method in the National Cartographic
      Institute. The results show that the average area of the lower complete denture's
      polished surface is 2.096 mm2, and the upper's is, 3644 mm2. The authors did find
      any not differences according to sexes.

PMID- 7821446
TI  - [Use of Dormicum (midazolam) injection in oral surgery under local anesthesia].
AB  - Authors report on the sedative anxiolytic and anterograde amnesia causing effect
      of "Dormicum", in connection with 170 dental and/or oral surgery interventions.
      Initial dose of Dormicum was 0.1 mg/body weight kgs,--necessary repetitions
      occurred with 0.02-0,03 mg/body weight kgs. In 75% of the patients an acceptable
      level of sedation developed by using 0.1 mg/body weight kgs. In more than 90% of
      the cases anterograde amnesia could be observed, which seemed to be the most
      important element of this kind of treatment.

PMID- 7821447
TI  - [Unilateral space-creating extraction in orthodontics].
AB  - Space maintaining extraction on one side is a controversial point in
      orthodontics, yet relevant references in literature are only few and far between.
      The author has summed up the attitudes towards the unilateral Space maintaining
      extraction by levelling. Among other things, he emphasizes the importance of
      avoiding extraction on one side, however when in one quadrant there is smaller
      room than that of a pre-molar would occupy, an extraction as a concession might
      be made. When making extraction distal removal is indicated (in such cases the
      extraction of a molar is also possible) and to avoid non-preferable deformities
      very soon a strong and rigid are needs to be applied. Teeth in situations which
      are not meant to be changed, should be fixed. Care should be taken that the
      central line will not be displace to the direction of extracting. Generally
      speaking, it is not possible to establish an excellent occlusion in the case of
      unilateral extraction. After the treatment, the wisdom tooth which pushes forward
      might cause the displacement of the central line. In the case of unilateral
      extractions, the patient should be reported on the visible consequences that
      might occur.

PMID- 7821448
TI  - [Possibilities of improving surface properties of medical implants 1].
AB  - The work is planned in three parts. The first reviews the various modification of
      the surface-treatment procedures for medical implants. A separate section deals
      with procedures involving the application of material or the removal of material,
      and those is which material is not applied or removed. Special consideration is
      paid to the surface-treatment procedures for facial or mandibular implants, and
      techniques involving calcium phosphate and hydroxylapatite coatings.

PMID- 7821449
TI  - [Combined use of Ceros-80 an lyodura in dental implantations].
AB  - The histological examination plays an important role in the determination of the
      clinical use of hydroxylapatite ceramics (HA). In the presented case, the
      periodontally compromised tooth was removed and the alveolus filled with HA and
      covered by Lyodura. 20 months later a blade type of implant was inserted, which
      was surrounded with HA again. At the time of the operation a biopsy was taken,
      and the subsequent histological examination showed a complete osseous healing.

PMID- 7821450
TI  - [Water absorption and water solubility of prosthetic materials].
AB  - Denture base materials investigated with using surface coating polymers fulfilled
      requirements of ISO Standards 1567 for water sorption and water solubility. The
      heat-cured polymer gave up water in a greater extent comparing to the cold-cured
      one. Further amount of water was retained by the surface treatment of coating. A
      five times increase of water solubility in samples of cold-cured resin was found
      comparing to the heat-cured ones. A significant decrease of water sorption was
      measured by using the surface coating.

PMID- 7821452
TI  - [Treatment of xerostomia with lactoperoxidase-containing mouthwashes and
      toothpaste].
AB  - The aim of the study was to determine the effect of a lactoperoxidase-
      hypothiocyanate enzyme system on the subjective complaints and symptoms of
      patients suffering from "dry mouth syndrome" with diseases of the oral mucosa.
      The objective changes in the oral microbiological flora and cytological pattern
      were also assessed. The lactoperoxidase-enzyme system-containing products--like
      Oralbalance gel (in combination with Biotene toothpaste)--seems to be a useful
      tool of choice for symptomatic therapy in patients, complaining of "dry mouth
      syndrome".

PMID- 7821451
TI  - [Study of the atrophy of the jaws].
AB  - Examining 230 edentulous patients, a significant degree of atrophy in the maxilla
      and mandible relatively often has been found. Atrophy could be detected more
      often in the mandible of female patients. For these forms of manifestation, among
      others, systemic causes: osteoporosis, diabetes and periodontal disease could be
      found. The results and their classification may help to draw the attention in the
      course of treatment to strong dissimilarities or similarities of the edentulous
      mouth. The degree of atrophy observed on both jaw-bones--among other factors--is
      significant for the planning and prognosis when indicating total prosthetic
      treatment.

PMID- 7821453
TI  - [Remembering Dr. Imre Foldvari (1894-1976)].

PMID- 7821454
TI  - Recurrent corneal erosion: clinical features.
AB  - The clinical features of a group of 30 patients with recalcitrant recurrent
      corneal erosions (i.e. those who failed to respond to conventional therapy) were
      evaluated. Associated ocular and facial abnormalities were documented. Meibomian
      gland dysfunction was present in all patients as manifest by dropout and
      inspissation of the meibomian glands, reduced tear film break-up time and debris
      in the tear film. Dropout of meibomian glands was present in 25 (83%) patients
      and was maximum in the medial half of the lid in 21 (84%) of these 25 patients.
      Tear film break-up time was reduced in all patients, being instant in 7 (23%),
      between 1 and 5 seconds in 22 (74%) and between 10 and 15 seconds in 1 (3%)
      patient. Superficial corneal abnormalities were present in 28 (93%) patients as
      manifest by maps, dots and fingerprints. Facial abnormalities such as
      telangiectasia, rhinophyma and acne rosacea were present in 22 (73%) patients.
      The findings of our study suggest an association between recalcitrant recurrent
      corneal erosions and meibomian gland dysfunction.

PMID- 7821455
TI  - Phototherapeutic keratectomy for recurrent corneal erosions.
AB  - Recurrent corneal erosion may be a difficult disorder to treat, with a number of
      patients suffering persistent symptoms despite conventional therapy. We present a
      series of 15 patients (17 eyes) who underwent excimer laser phototherapeutic
      keratectomy (PTK) for recurrent corneal erosion. In 9 patients a previous episode
      of corneal trauma could be identified, while in 6 (8 eyes) the problem had
      occurred spontaneously. The mean duration of symptoms prior to PTK was 13 months
      (range 6-60 months). All patients had received lubricant ointments, 7 had tried
      bandage contact lenses and 4 had undergone epithelial debridement with no
      amelioration of their symptoms. The affect area of epithelium was removed and a
      20-30 pulse (5-7 microns) ablation was performed to Bowman's membrane. Great care
      was taken to avoid the edges of treatment zones from encroaching on the axial
      cornea. In 11 patients (13 eyes) there was a marked improvement in symptoms post
      operatively with no recurrences. The mean follow-up was 11 months (range 6-24
      months). Four patients experienced recurrent episodes 3-6 months after PTK and 2
      have subsequently been retreated, 1 of whom has been symptom-free for 12 months.
      Post-operative best corrected visual acuity was unaltered in 9 eyes and improved
      by at least one Snellen line in 8 eyes. Excimer laser PTK appears to be a safe
      and promising procedure for recurrent corneal erosion in cases refractory to
      medical treatment. Further studies are indicated to compare its effectiveness
      with established surgical procedures.

PMID- 7821456
TI  - Oral tetracycline in the treatment of recurrent corneal erosions.
AB  - We report the results of a prospective, randomised controlled, 24 week trial to
      assess the efficacy of oral tetracycline and oral tetracycline with topical
      prednisolone in the treatment of recalcitrant recurrent corneal erosions, i.e.
      those which fail to respond to standard therapy. A total of 30 patients were
      randomly allocated to either standard treatment (group A), standard treatment and
      oral tetracycline (group B) or standard treatment, oral tetracycline and topical
      prednisolone (group C). Treatment groups B and C were instructed to perform daily
      lid hygiene. There was a significant reduction in the number of recurrent corneal
      erosions during the 24 week study period in group B (p = 0.04) and in group C (p
      = 0.0003) but not in group A (p = 0.66). There was a significant difference in
      the accelerated healing time of recurrent corneal microerosions between groups A
      and B (p = 0.001) and between groups A and C (p = 0.001). There was a significant
      improvement in the symptom scores during the study in treatment groups B and C (p
      = 0.005) but not in group A (p = 0.15). We conclude that lid hygiene and oral
      oxytetracycline 250 mg twice daily for 12 weeks with or without topical
      prednisolone for the first 7 days is beneficial in the management of recalcitrant
      recurrent corneal erosions.

PMID- 7821457
TI  - Vascular changes over trabeculectomy blebs.
AB  - Low-dose anterior segment fluorescein angiography was performed on 10 eyes before
      and after trabeculectomy with a limbal-based conjunctival flap. Post
      trabeculectomy angiography shows that all successful trabeculectomies have an
      area of decreased capillary vascular perfusion over the bleb site not
      coincidental with the area of the bleb and that there is delayed filling of
      vessels running over the bleb.

PMID- 7821458
TI  - The predictive value of post-operative intraocular pressures following
      trabeculectomy.
AB  - The value of post-operative intraocular pressure (IOP) in predicting the outcome
      of trabeculectomy was investigated in a retrospective study of single eyes of 203
      Caucasian patients with uncomplicated chronic open angle glaucoma from the
      Birmingham and Midland Eye Hospital. Post-operative IOPs were recorded on day 1,
      at 2 weeks, and at 3, 6, 12 and 24 months. Surgical failure, defined as an IOP of
      21 mmHg or above throughout the study period, occurred in 66 eyes by 24 months
      (32.5% failure). Discriminant analysis for the first day post-operative IOP
      showed a reliability of prediction of success (RPS) and failure (RPF) of 76.4%
      and 74.4% respectively, with an accuracy of prediction of success (APS) and
      failure (APF) of 92.6% and 42.6%. At 2 weeks, APS remained high (90.3%) and APF
      increased with time (63.2%). Certainty of success prediction at any stage is high
      and certainty of failure prediction becomes greater with time. In terms of IOP on
      the first post-operative day, 92.6% of successes may be correctly predicted if
      the IOP < 17 mmHg and 42.6% of failures may be predicted if the IOP > or = 17
      mmHg. This study suggests that identification of patients at risk of failure on
      the basis of IOP in the early post-operative period is possible and that closer
      follow-up and early medical or surgical intervention may be indicated.

PMID- 7821459
TI  - Simultaneous bilateral trabeculectomy.
AB  - In a retrospective study, 24 patients who had undergone simultaneous bilateral
      trabeculectomy over a 6-year period were reviewed. The duration of disease was at
      least 2 years, indicating that surgery was not performed as a primary procedure.
      No patients suffered complications leading to bilateral blindness, although 6
      (25%) patients had reduced vision in both eyes at the first postoperative visit,
      with 3 (13%) worse than 6/36 binocularly. There was no evidence of an asymmetric
      response in the fall in intraocular pressure following trabeculectomy, after a
      mean follow-up of over 3 years. Compared with a matched group of patients
      undergoing unilateral trabeculectomy, the simultaneous bilateral group had a
      similar period of hospital stay. However, this was no shorter than that found in
      a group having staged bilateral surgery during the same admission, over the same
      study period. When separate admissions were required for bilateral drainage
      operations, though, there was a significant increase in the total length of
      inpatient stay. No convincing advantage was found for simultaneous bilateral
      trabeculectomy.

PMID- 7821460
TI  - A comparison of the efficacy of Holmium laser sclerostomy ab externo versus
      trabeculectomy in the treatment of glaucoma.
AB  - We compared 15 patients who had undergone Holmium laser sclerostomy ab externo
      with 15 who had had trabeculectomy. In the short term, laser sclerostomy led to
      adequate control of intraocular pressure, but in the longer term it compared
      unfavourably with trabeculectomy in terms of efficacy, complications and
      reoperation rate. At 1 year follow-up, 8 patients in the laser group had had to
      undergo a second operation compared with none in the control trabeculectomy
      group, and 7 were still on glaucoma medication compared with 2 in the control
      group. Iris prolapse into the internal sclerostomy ostium within 2 months
      accounted for most failures, and was only partially amenable to Nd:YAG peripheral
      iridectomy. This common complication seems to be related to anterior chamber
      depth. There also appears to be a tendency for blockage of the sclerostomy with
      cellular or fibrinous debris. Recent literature is reviewed and modifying
      strategies discussed.

PMID- 7821461
TI  - Improving the sensitivity of the OKP visual field screening test with the use of
      neutral density filters.
AB  - Oculokinetic perimetry (OKP) has been developed to screen for glaucomatous field
      loss but has relatively poor sensitivity when compared with threshold perimetry.
      Forty-two eyes from 42 patients with glaucomatous field loss on Humphrey
      threshold perimetry and 32 normals performed hand-held OKP under controlled
      conditions of refraction and lighting. Those who passed the standard test had
      their OKP cutoff determined with increasing neutral density filters (NDFs) at a
      new point 15 degrees from fixation in the inferotemporal field (where first
      glaucomatous defects are rarest). OKP was then repeated with a NDF that increased
      the ambient light by 0.3 log units from cut off. Of the 16 glaucomatous eyes to
      pass standard OKP, 9 failed the NDF test, improving the sensitivity from 62% to
      83% (p < 0.05). These 9 eyes had field defects that were significantly less
      severe (mean defect 4.85 vs 7.91 (p < 0.05) and corrected pattern standard
      deviation 4.12 vs 7.00 (p < 0.05) and were from younger patients (mean age 56 vs
      66 years; p < 0.05) than those who failed standard OKP. None of the 32 normals
      failed standard OKP and only 1 of 32 failed the NDF test. The use of NDFs to
      customise OKP, producing essentially a staged suprathreshold contrast sensitivity
      test, appears to increase the sensitivity of the OKP screener without degrading
      its specificity, particularly in younger subjects.

PMID- 7821462
TI  - Clinical experience with a fixed dose combination therapy of timolol and
      pilocarpine used twice daily in the management of chronic open angle glaucoma.
AB  - Twenty-five eyes of 25 patients with primary chronic open angle glaucoma deemed
      controlled for 12 months were converted from timolol 0.25% or 0.5% b.d. and
      pilocarpine 2% q.i.d. to a combination drop (TP2) of combined timolol 0.5% and
      pilocarpine 2% given b.d. Mean intraocular pressures (IOP) were 18.68 +/- 2.84
      mmHg at 1 month, 18.81 +/- 2.56 mmHg at 3 months and 18.56 +/- 2.01 mmHg at 6
      months. These values were significantly higher than the initial IOP of 17.48 +/-
      2.2 mmHg (p values 0.0006, 0.0001 and 0.0004 respectively). However, 1 month
      following reconversion to initial therapy the IOP was 17.68 +/- 2.67 mmHg, which
      was not significantly higher than the initial IOP (p = 0.46). In addition, of 8
      eyes uncontrolled during the course of the study, 6 became controlled following
      reconversion to initial treatment. Combination therapy of TP2 b.d. cannot be
      recommended to control IOP satisfactorily in patients maintained on timolol 0.25%
      or 0.5% b.d. and pilocarpine 2% q.i.d.

PMID- 7821463
TI  - Cyclocryotherapy for chronic glaucoma after vitreoretinal surgery.
AB  - The case records were reviewed of 27 patients with chronic glaucoma after
      vitreoretinal surgery who underwent 28 cyclocryotherapy procedures between March
      1987 and March 1992. The average intraocular pressure after 3 months was between
      11.0 and 13.3 mmHg with an average fall of 24-26 mmHg. More than 85% had
      intraocular pressures of less than 21 mmHg after 3 months; 28% were hypotonic
      (IOP < 6 mmHg). Six months postoperatively, 68% maintained or had improved
      vision. The hypotonic eyes were found to have deterioration in vision more
      frequently than those with an intraocular pressure > 5 mmHg (57% compared with
      24%). The odds of a hypotonic eye losing vision were 4.27 times greater than for
      a non-hypotonic eye. Cyclocryotherapy was successful in relief of pain in all 4
      eyes which were painful pre-operatively.

PMID- 7821464
TI  - Circumferential argon laser photocoagulation for prevention of retinal
      detachment.
AB  - Circumferential argon laser photocoagulation was administered as preventive
      treatment for retinal detachment in 53 eyes with extensive areas of lattice
      degeneration and/or retinal breaks and at least one additional high-risk factor
      for retinal detachment. Laser burns were applied in several continuous rows 360
      degrees around the peripheral retina at the junction between the posterior border
      of the lesions and the unaffected retina. The retina posterior to the treated
      areas remained attached in 51 eyes (96.2%) during a mean follow-up period of 85.8
      months (range 6 months to 18 years). The treatment did not affect visual acuity.
      The only complication was the appearance in 2 eyes (3.8%) of a delicate
      epiretinal membrane which, however, did not require surgical intervention.

PMID- 7821465
TI  - Indirect diode laser treatment for stage 3 retinopathy of prematurity.
AB  - Eight infants with stage 3+ retinopathy of prematurity (ROP) were treated using
      the diode laser through a binocular indirect ophthalmoscope. Two infants with
      zone I disease were treated prethreshold as soon as the signs of plus disease
      developed. Successful regression was achieved in all cases, though 3 infants
      required repeat treatment. All infants were followed up for a minimum of 3
      months. Keeler acuity scores were in the normal range in 4 of the 8 infants.

PMID- 7821466
TI  - Axial length biometry in infants with retinopathy of prematurity.
AB  - Ultrasound axial length measurements were obtained on infants under a birthweight
      of 1500 g or 32 weeks gestation undergoing screening for retinopathy of
      prematurity (ROP). A total of 496 readings were obtained on 171 infants between
      32 and 41 weeks post-conceptual age. Other details recorded were maximum stage of
      acute ROP, birthweight, gestational age, sex, and biparietal and occipitofrontal
      head diameters. The relationship of these variables to axial growth of the eye
      was examined using analysis of covariance with a repeated measures approach. Mean
      axial length increased from 15.27 mm to 16.65 mm in the left eye during this
      period. Following adjustment for repeated readings a growth rate of 0.18 mm/week
      was obtained for both eyes. Male infants were found to have longer axial lengths
      despite correction for birthweight, gestation and head size (p < 0.0001 right and
      left). Higher stages of acute ROP were also associated with shorter axial length
      (p < 0.05 for all stages of both eyes) but the rate of growth during the study
      period did not demonstrate significant differences between stages. Stage 3
      infants reaching the threshold for cryotherapy had shorter axial length than
      stage 3 infants not receiving treatment. The effect of prematurity on the growth
      of the eye and the significance of these findings with respect to the subsequent
      development of refractive errors in premature infants are discussed.

PMID- 7821467
TI  - Three subgroups of patients from the United Kingdom with Leber hereditary optic
      neuropathy.
AB  - Variations in classic Leber hereditary optic neuropathy (LHON) include recovery
      of vision and association with other neurological abnormalities. Sixteen multi
      generational Australian families originating from the United Kingdom with LHON
      were studied by the one examiner, using the same protocol. In particular,
      recovery of vision and other neurological abnormalities were noted. One very
      large family (Tas2) and one small family (Vic2) were found to have frequent
      recovery of vision (50% of patients). They both had the 14484 T to C mutation in
      their mitochondrial DNA (mtDNA). One apparently unique family (Qld1) was found to
      have frequent juvenile encephalopathy and peripheral neurological signs. They had
      the 4160 T to C and 14484 T to C mutations. The remaining 13 families rarely
      showed visual recovery or associated neurological abnormalities. They had the
      common 11778 G to A or the 3460 G to A mutations. Thus mitochondrial genotypes in
      LHON are associated with variable phenotypes.

PMID- 7821468
TI  - Detection of diabetic retinopathy by scanning laser ophthalmoscopy.
AB  - A scanning laser ophthalmoscope (SLO) was used to examine the fundi of 54
      diabetic patients through undilated pupils and the results compared by an
      experienced ophthalmologist with clinical examination through dilated pupils to
      assess the effectiveness of the SLO in detecting diabetic retinopathy. Whilst the
      SLO was not as good at detecting cotton wool spots and subtle intraretinal
      microvascular abnormalities, it did not miss any active new vessel formation and
      all eyes needing treatment would have been referred.

PMID- 7821469
TI  - Meta-analysis of systemic anti-fibrinolytics in traumatic hyphaema.
AB  - We report a meta-analysis of randomised, controlled, clinical trials of systemic
      anti-fibrinolytics in traumatic hyphaema. Outcome measures were rate of secondary
      haemorrhage and final visual acuity. An estimate of the overall odds ratio for
      each outcome measure was calculated both by combining the logarithms of the odds
      ratios, and by the Mantel-Haenszel method. The results confirm a beneficial
      effect of systemic antifibrinolytics on the rate of secondary haemorrhage, but
      not on final visual acuity.

PMID- 7821470
TI  - The efficacy of systemic corticosteroids in sight-threatening retinal vasculitis.
AB  - This study was undertaken to assess the efficacy of a standard regime of high
      dose systemic oral corticosteroids in the management of retinal vasculitis. The
      study was performed because the single most common reason for referral to our
      specialist clinic is the apparent failure of patients to respond to a course of
      systemic steroids, which in most cases appeared to be due to an inadequate
      initial dose. A retrospective study of 29 patients (30 treatment episodes) with
      sight-threatening retinal vasculitis managed initially with high-dose systemic
      steroids was evaluated 1 year after treatment. Patients included in the study all
      started treatment with > or = 1 mg/kg prednisolone and remained on a high steroid
      dose (> or = 40 mg prednisolone) for at least 5 weeks. No patient was on any
      other immunosuppressive agent at the start of the study. Therapeutic success for
      this regime, as judged by improvement in visual acuity, was 60%, improving to 77%
      with addition of other immunosuppressive agents. Eight patients required
      additional immunosuppressives. Although documented side-effects of steroids were
      common (50% of cases managed on steroids alone), in only 5 patients were they
      therapeutically important. Twelve of the 22 patients managed on high-dose
      steroids alone were off treatment at 12 months. There was no correlation at any
      stage between visual acuity, activity index or relapses and the final visual
      outcome at 12 months. Seven cases had a poor visual outcome and the causes for
      this included relapse in the twelfth month of follow-up, persistent cystoid
      macular oedema and lens opacity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7821471
TI  - Severe granular dystrophy: a pedigree with presumed homozygotes.
AB  - Three siblings with severe granular corneal dystrophy are described. They are
      most likely to be homozygous for the dominantly inherited gene. They are
      offspring of a consanguineous marriage, with both parents affected with corneal
      dystrophies. The case reports describe the severe course of this condition,
      requiring multiple grafting procedures. Clinical pictures of the family are
      shown.

PMID- 7821473
TI  - Ivermectin and onchocercal optic neuritis: short-term effects.
AB  - In 1982 the macrocyclic lactone, ivermectin, was first tested in human patients
      with onchocerciasis. It has since undergone phase I to IV trials and is now being
      widely distributed in onchocercal areas. The previous microfilaricide,
      diethylcarbamazine citrate (DEC), is known to precipitate or exacerbate active
      optic neuritis in some onchocercal patients, as part of a wider inflammatory
      response (the Mazzotti reaction). Ivermectin may also cause a mild reaction,
      especially in people with high microfilarial loads. Few data are available
      concerning the effect of ivermectin on active optic neuritis. A large,
      randomised, double-masked, phase IV trial is reported. Individuals were screened
      for evidence of optic nerve disease (OND), and those identified as possible cases
      of OND underwent detailed ophthalmic examination, including fluorescein
      angiography, before being dosed with ivermectin or placebo. A total of 6831
      persons were screened of whom 856 (13%) underwent angiography prior to dosing. At
      7-14 days after dosing an attempt was made to re-examine 50% of adults over the
      age of 20 years, including all those with OND. Six hundred and eighty-eight
      repeat or new angiograms were performed. During this period, 5 new cases of
      active optic neuritis and one case of exacerbation of existing optic neuritis
      were identified. Five of these individuals had received placebo and one
      ivermectin. Two individuals with optic neuritis before dosing had improved after
      7-14 days. One had received placebo, the other ivermectin. Ivermectin does not
      appear to precipitate or exacerbate optic neuritis at a period of 7-14 days.

PMID- 7821472
TI  - Lens hardness in mature cataracts.
AB  - A cataract is said to be mature when all the cortical fibres become opaque.
      Depending on the pathophysiological processes that cause the cortical fibre
      opacification this phenomenon may be associated with a varying degree of nuclear
      sclerosis. A relationship between lens hardness and degree of nuclear sclerosis
      in non-mature cataracts has been demonstrated previously. This study aimed to
      investigate the relationship between the hardness of mature cataracts and the
      transmitted nuclear colour, age and rate of progression of the cataract. Thirty
      eight patients with mature cataracts were assessed prior to extracapsular
      cataract surgery. The nuclear colour that was transmitted through the opaque
      cortex was graded using reference photographs. Age and duration of visual
      symptoms were recorded and lens hardness was measured by a specially designed
      lens guillotine. Multivariate analysis of data indicates a relationship between
      hardness of a mature cataract and the transmitted nuclear colour and age
      (adjusted R2 = 0.59). There is also a tendency for hardening of the lens as the
      duration of visual symptoms increases. By considering these clinical markers, the
      cataract surgeon can estimate the hardness of the lens and therefore its
      suitability for phacoemulsification.

PMID- 7821474
TI  - Use of topical diclofenac in association with external ocular compression.
AB  - This study investigated the effect of pretreatment with topical diclofenac 0.1%
      on the changes in intraocular pressure (IOP) associated with use of an external
      ocular compression device. The IOP reduction in eyes receiving pretreatment was
      significantly greater than in controls after 40 minutes of compression, and the
      recovery in IOP after removal of the compression device was significantly
      reduced. We conclude that the IOP rise after such compression is largely
      prostaglandin mediated, and suggest that use of ocular compression devices is
      associated with marked intraocular prostaglandin release.

PMID- 7821476
TI  - Subclinical operating microscope retinopathy: the use of static perimetry in its
      detection.
AB  - Focal retinal pathology and dysfunction as a sequel to manifest damage due to
      operating microscope illumination is well recognised. We wished to determine
      whether retinal dysfunction could be identified in the absence of clinically
      visible lesions. We therefore have conducted a prospective controlled study on 36
      patients undergoing cataract surgery and 27 control subjects. A Wild M690 zoom
      operating microscope was used for each procedure. No filters were used. The
      Humphrey visual field equipment was employed to determine threshold retinal
      sensitivity at predetermined loci above and below fixation in both groups. No
      clinically visible retinal lesions were seen in any patient. However, post
      operative investigation revealed a statistically significant depression in
      retinal sensitivity at points most exposed to operating microscope illumination
      (p < 0.05). This was most noticeable following longer total operating times and
      in patients with the longest time intervals between lens extraction and
      completion of the procedure. It is concluded that operating microscope position
      and centration, and the position of the eye, should be adjusted to place the
      image of the illuminating element away from the foveola. Also retinal
      illumination should be kept to a minimum, particularly after an intraocular lens
      has been implanted.

PMID- 7821475
TI  - A comparison of amethocaine cream with lignocaine-prilocaine cream (EMLA) for
      reducing pain during retrobulbar injection.
AB  - A prospective, randomised, double-masked, placebo-controlled study was carried
      out on 169 patients undergoing cataract extraction to compare the topical
      anaesthetic cream amethocaine with EMLA (eutetic mixture of local anaesthetic,
      lignocaine and prilocaine) and placebo in reducing pain during retrobulbar
      injection. Fifty-eight patients received EMLA, 55 amethocaine and 56 the placebo.
      The pain was assessed objectively by the anaesthetist and subjectively by the
      patient. Significantly lower pain scores were observed in those patients who had
      amethocaine (p < 0.001) or EMLA (p < 0.005) in comparison with those who had
      placebo, but there was no statistical difference between amethocaine and EMLA (p
      > 0.1; t-test). No systemic or local side-effects were encountered in any group.

PMID- 7821477
TI  - Back pain in ophthalmologists.
AB  - A questionnaire regarding the working practices and incidence of back pain was
      sent to all 498 consultant ophthalmologists in the United Kingdom. Three hundred
      and twenty-five (65.3%) questionnaires were analysed by time spent in speciality,
      and time spent operating each week. One hundred and seventy-four ophthalmologists
      (54%) had significant attacks of back pain, with the longest-serving consultants
      having an increased incidence. The number and duration of acute attacks increased
      with years in speciality but was unrelated to time spent operating. Treatment
      included analgesics in 97 (56%), physiotherapy in 40 (23%), and 'alternative'
      medical treatment including osteopathy and chiropraxy in 14 (8%); no treatment
      was needed in 56 (32%). Investigation and treatment increased with years spent in
      speciality, 49 (28%) seeking medical advice, usually from a specialist, and 69
      (39%) requiring further investigations including plain radiographs, CT scans,
      myelograms and MRI scans. Nine surgeons needed surgery for back pain.

PMID- 7821478
TI  - Learning phacoemulsification: the surgeon-in-training.
AB  - With the increasing trend towards phacoemulsification a perceived increased
      complication rate during the learning curve gives rise to a dilemma as to the
      best stage at which a surgeon-in-training can safely learn the technique. We
      prospectively analysed the complications and visual outcome of the first 160
      phacoemulsification procedures performed by three surgeons-in-training. The main
      outcome measures included posterior capsule tear, vitreous and nuclear loss,
      surgical re-intervention rate and visual outcome. Posterior capsule tear occurred
      in 7 eyes (4.4%) and vitreous loss in 6 (3.8%). No nucleus was lost in the
      vitreous. Surgical re-intervention was required in 1 eye. Best corrected visual
      acuity was 6/12 or better in 88% of eyes. These results compare favourably with
      reports of surgeons-in-training learning extracapsular surgery and also with
      recently reported phacoemulsification series. This study indicates that with
      careful case selection and supervision phacoemulsification can be a safe
      procedure.

PMID- 7821479
TI  - Giant retinal tear caused by hydraulic injury.

PMID- 7821480
TI  - Pyogenic granuloma or lobular capillary haemangioma.

PMID- 7821481
TI  - Paget's disease presenting with exophthalmos.

PMID- 7821482
TI  - Bacterial keratitis following excimer laser photorefractive keratectomy: a case
      report.

PMID- 7821483
TI  - Blepharophimosis syndrome: an atypical case.

PMID- 7821484
TI  - Vitelliform macular dystrophy: a cause of macular holes with retinal detachments.

PMID- 7821485
TI  - Cytokine levels in amniotic fluid and inflammatory changes in the placenta from
      normal deliveries at term.
AB  - Cytokine levels in amniotic fluid have been shown to increase towards term in
      normal pregnancies, and may play a regulatory role in parturition by stimulating
      the local production of prostaglandins. The work reported in the present paper
      was conducted in order to test the hypothesis that the increased cytokine levels
      may be induced by a subclinical inflammatory reaction in intrauterine tissues.
      The concentrations of tumor necrosis factor (TNF), interleukin 1 (IL-1),
      interleukin 2 (IL-2) and interleukin 6 (IL-6) were determined in samples of
      amniotic fluid from 38 women in delivery at term, after a clinically normal
      pregnancy. In 33 of the cases, tissue material was available for histological
      examination. In these, the extent of inflammatory cell infiltration was assessed
      in the fetal membranes, placenta and umbilical cord. A close interrelation was
      observed between the levels of the mediators typically released during
      inflammatory processes (TNF, IL-1, IL-6). Frank chorioamnionitis was not found in
      any of the histological specimens, although most placentae showed varying degrees
      of granulocyte infiltration in the fibrin layer under the chorion, sometimes also
      in the chorionic membrane. The degree of such leukocytic infiltration correlated
      positively with the levels of TNF, IL-1 and IL-6. These findings lend support to
      the hypothesis that a low-level inflammatory process may be a normal occurrence
      in the term placenta, and that this process may induce the production of
      cytokines, which, in turn, may play a role in the regulation of parturition. Such
      inflammation could be due to exposure of the fetal membranes to microbial
      material from the vagina, as the cervix dilates towards term.

PMID- 7821486
TI  - Urological complications associated with caesarean section.
AB  - We analysed 1438 deliveries by caesarean section (CS) with regard to urological
      complications such as urological infections and urinary tract injuries. There
      were five accidental cystotomies, but no ureteral injury and no urogenital
      fistula. Serious urological complications are rare and further complications,
      such as urogenital fistulae and urosepsis, can be avoided if the injury is
      recognised and repaired properly during the operation. On the other hand,
      significant bacteriuria after CS is common. It was found in > 11% of the
      patients, most probably because of routine catheterization. Symptomatic urinary
      tract infection (UTI) must be treated as soon as symptoms appear, but routine
      antibiotic prophylaxis is not recommended.

PMID- 7821487
TI  - The prevalence of cocaine abuse during pregnancy in Barcelona.
AB  - The aim of our study was to determine the prevalence of cocaine abuse, by means
      of positive urine toxicology screens or targeted questionnaire, among women in
      labor at our hospital. The prospective study included 1773 women who delivered
      consecutively in our institution. All of them underwent a standardized
      questionnaire including drug use and demographic data. Urine samples were
      obtained during labor. Urine toxicology screens for cocaine and its metabolites,
      opiates, and ethanol were performed by enzyme multiplied immunoassay technique.
      Information was coded in order to maintain anonymity. Among the 1773 women in
      labor we screened, the mean age was 27.8 years and the overall prevalence of a
      positive questionnaire for cocaine was 0.3% and a positive urine toxicology was
      0.8%. Results by drug and by demographic items are analysed. There was a
      substantial denial of cocaine use among the toxicologically positive patients,
      since only 43% of them referred its use at any time during pregnancy, in
      conclusion, the use of illicit drugs is common among pregnant women in our
      institution, but cocaine does not seem to be as prevalent as it is in the USA,
      while in the labor room most women with a positive test do not refer the use of
      the drug. Urine toxicology screening increases the rate of detection of substance
      abuse in this population of women. These studies are necessary to target
      educational programs among pregnant women.

PMID- 7821488
TI  - The use of the hand-grip test for predicting pregnancy-induced hypertension.
AB  - To assess the potential of the hand-grip exercise test as a screening test for
      pregnancy-induced hypertension a prospective non-interventional study was carried
      out in a teaching hospital antenatal clinic. The hand-grip test was performed on
      200 nulliparous, normotensive subjects at 28-32 weeks gestation. The main outcome
      measurement was the subsequent development of pregnancy-induced hypertension or
      pre-eclampsia. The sensitivity of the technique in predicting pregnancy-induced
      hypertension was 53% and the specificity was 94%. The sensitivity of the test in
      predicting pre-eclampsia was 80% and the specificity was 92%. The time-consuming
      nature of the hand-grip test probably restricts use of the technique to research
      studies where selection of a high-risk group is required.

PMID- 7821489
TI  - Results of curettage for postmenopausal vaginal bleeding in women treated with
      tamoxifen and megestrol acetate for progressive metastatic breast carcinoma.
AB  - Tamoxifen and megestrol acetate are used as a hormonal treatment for metastatic
      breast carcinoma. It is suggested that the use of tamoxifen may induce
      endometrial cancer. In this article we describe nine patients under hormonal
      treatment for metastatic breast cancer with, firstly, tamoxifen and, later,
      megestrol acetate. These nine patients all had symptoms of postmenopausal vaginal
      blood loss during therapy with megestrol acetate, an indication to perform a
      diagnostic dilatation and curettage. By histopathological examination the
      curettings showed a decidualized stroma with an infiltration of lymphocytes, some
      plasma cells and many eosinophils. In none of the patients was atypical
      hyperplasia or malignancy found. The dilatation and curettage had also a
      therapeutic effect, since only one of the patients still had complaints, while
      the other eight did not complain of postmenopausal bleeding again. We review the
      literature and discuss the value of a diagnostic dilatation and curettage.

PMID- 7821490
TI  - Laparoscopic management of malignant ovarian cysts: a 78-case national survey.
      Part 1: Pre-operative and laparoscopic evaluation.
AB  - This paper reports a retrospective multi-institutional French survey carried out
      in 1992 to determine the incidence of laparoscopic management of malignant
      ovarian cysts. Of 5307 ovarian lesions treated endoscopically, 78 were malignant
      (1.47%) including 60 borderline tumors and 18 ovarian cancers. In 33% of cases
      preoperative diagnosis indicated that the tumor was benign. Preoperative findings
      were suspicious in 59%. Laparoscopic treatment was puncture in 23% of cases,
      partial exeresis in 51% and total removal in 26%.

PMID- 7821491
TI  - Vulvar sarcoma: clinical implications.
AB  - This is a review of the histories of 47 patients with vulvar sarcoma, consisting
      of leiomyosarcoma (25), malignant fibrous histiocytoma (5), epithelioid sarcoma
      (8), dermatofibrosarcoma protuberans (9), including 7 from our own institute.
      When compared to the biological behaviour of sarcomas from other anatomic sites
      of the body, no essential differences were found. The prognosis after the
      appearance of regional or distant recurrence was poor and prevention of local
      recurrence by wide excision was the best way to improve the prognosis of
      leiomyosarcoma and dermatofibrosarcoma protuberans. However, the poor prognosis
      of epitheloid sarcoma did not change. Elective treatment of regional lymph nodes
      was not indicated in the four tumor types discussed and dissection of metastatic
      inguinal nodes was rarely beneficial. However, distressing local problems were
      prevented in a patient with epithelioid sarcoma and lasting benefit was seen in a
      patient with malignant fibrous histiocytoma who developed an inguinal metastasis
      after a 3-year disease-free interval. The beneficial effect of resection of
      pulmonary metastasis needs more attention.

PMID- 7821492
TI  - Amniotic fluid erythropoietin levels in normal and Down's syndrome pregnancies.
AB  - The aim of this study was to measure the levels of erythropoietin in amniotic
      fluid from normal and trisomy 21 pregnancies at 10 to 20 weeks gestation. Samples
      of amniotic fluid were collected from 142 women with singleton pregnancies after
      genetic amniocentesis; 110 had a normal fetal karyotype and 32 had trisomy 21.
      Erythropoietin was measured using a double antibody radioimmunoassay. Amniotic
      fluid erythropoietin levels in normal pregnancies increased from 10 weeks (mean
      3.2 mU/ml; range < 2.0-6.3 mU/ml) to 20 weeks gestation (mean 7.9 mU/ml; range
      2.0-11.5 mU/ml). There was a significant linear correlation between gestational
      age and erythropoietin levels (r = 0.543; P < 0.0001). For the 32 patients with
      trisomy 21 pregnancies the median multiple of the median (MoM) was 1.11 (range
      0.42-2.1). There was no difference between erythropoietin levels in amniotic
      fluid from normal and Down's syndrome pregnancies (U = 2352, P = 0.75, 95% CI = 
      0.11, 0.18); (Mann-Whitney U-test).

PMID- 7821493
TI  - Therapeutic strategies in cervical pregnancy.
AB  - Cervical pregnancy is a rare condition associated with a high maternal morbidity
      rate. Standard recommendations for the management of this ectopic pregnancy are
      not available. This paper presents a case report and reviews the respective
      literature. In many cases hysterectomy was the ultimate solution. In order to
      avoid hysterectomy chemotherapy using methotrexate has been suggested. Local
      injections of prostaglandins or vasopressin have also been proposed. Based on
      data collected from the literature and our own experience it is concluded that
      the management of cervical pregnancy requires individualized therapeutic
      strategies to minimize the rate of hysterectomies.

PMID- 7821494
TI  - Intra-partum fetal death due to thrombosis of the ductus venosus: a
      clinicopathological case report.
AB  - Thrombosis of the umbilical cord vessels is a rare but life-threatening event,
      usually leading to the death of the fetus. This report presents a case of an
      intra-partum fetal death due to thrombosis of the ductus venosus, hitherto not
      described in the literature. Labour was induced with intravenous oxytocin in a 21
      year-old nulliparous woman because of postmaturity at 43 weeks gestation. Abrupt
      fetal bradycardia developed at 5 cm dilatation and fetal demise occurred within
      minutes without any sign of abruptio placentae or uterine hyperactivity. A
      cesarean section was performed because of failure to deliver the macrosomic fetus
      by vacuum extraction. On autopsy a fresh occlusive thrombus was found at the
      beginning of the ductus venous in the portal sinus. Maternal and fetal risk
      factors known to be associated with umbilical cord thrombus formation were
      excluded. Repeated assessment of Bishop scores is thought to have caused local
      infection of the membranes at the internal cervical os, resulting in general
      amnionitis and vasculitis of the umbilical cord. Secondary to the infection
      thrombus formation took place either primarily in the portal sinus and ductus
      venosus or in the umbilical vein with subsequent detachment and embolisation into
      the portal sinus, therewith occluding the ductus venosus leading to fetal death.

PMID- 7821495
TI  - Prolonged premature rupture of membranes in the preterm infant: a 7 year study.
AB  - AIM: To review the outcome of infants born following prolonged and preterm
      rupture of the membranes. DESIGN: retrospective and partially prospective
      observational study. SETTING: babies born in and referred to a tertiary neonatal
      centre. PATIENTS: 117 preterm infants, median gestation (range) = 29.5 (25-36)
      weeks, seen over a 7 year period with membranes ruptured for more than 4 days;
      median (range) = 9 (4-119) days. OUTCOME MEASURES: survival and cause of death,
      compression deformities, pulmonary hypoplasia and infection. RESULTS: 23 infants
      died, 11 from pulmonary hypoplasia and 11 as a direct consequence of prematurity
      (3 from hyaline membrane disease, 7 from bronchopulmonary dysplasia and one from
      necrotising enterocolitis developed on day 17). One infant had a lethal
      congenital abnormality and died untreated of overwhelming infection. No other
      infants died of infection. 94% of infants were treated with broad-spectrum
      antibiotics after birth. Compression deformities were seen in 25 infants: median
      duration of membrane rupture 28 days, range 4-119. In those without deformity,
      median duration was 7 days, range 4-105. Sixteen infants had pulmonary hypoplasia
      (median 31, range 14-119), 11 died (median 37, range 21-112) and five survived
      (median 23, range 14-119). Although the median duration of membrane rupture in
      infants dying of pulmonary hypoplasia was longer than in those who did not have
      hypoplasia (31 compared to 7 days), 13 of 27 (48%) of infants whose membranes
      were ruptured for 4 weeks and 4 of 7 (57%) whose membranes were ruptured more
      than 70 days survived. CONCLUSION: death from pulmonary hypoplasia is a much more
      serious problem following preterm prolonged membrane rupture than is infection.
      Pulmonary hypoplasia is not inevitable even after prolonged periods of membrane
      rupture.

PMID- 7821496
TI  - The effect of fetal infection with human immunodeficiency virus type 1 on
      birthweight and length of gestation. SIGO Study Group of HIV Infection in
      Pregnancy.
AB  - We sought to evaluate the effect of vertical transmission of human
      immunodeficiency virus type 1 (HIV-1) on birthweight and length of gestation. For
      this purpose we used maternal and pregnancy data of 559 HIV-1-seropositive
      pregnant women delivered at 13 Italian centers from 1985 to 1991. The mother-to
      child transmission rate of HIV infection was 18.2% (84/461). After adjustment for
      potential confounders with multiple linear regression analysis, there were no
      differences in birthweight, gestational age, and proportion of expected
      birthweight (observed birthweight/expected birthweight) between infected and
      uninfected children. Intravenous drug abuse during current pregnancy was the
      factor which correlated best with a reduction in birthweight (mean reduction,
      214.4 g; 95% confidence interval (CI), 61.7-367.1), length of gestation (mean
      reduction, 9.3 days; 95% CI, 3.9-14.7) and proportion of expected birthweight
      (mean reduction, 12.1%; 95% CI, 4.7-19.5%). In our population, HIV-1 infection of
      the fetus has little effect on length of gestation and birthweight.

PMID- 7821497
TI  - Risk factors for spontaneous preterm birth in a Saudi population.
AB  - Preterm birth (< 37 weeks completed gestation), the primary predictor of infant
      morbidity and mortality, can result from diverse biologic and sociodemographic
      variables. A case-control study was undertaken to determine risk factors that
      were significantly associated with preterm birth in our population. Pertinent
      data were collected by structured interviews with eligible subjects and by
      medical record abstraction. The study population consisted of 118 mothers of
      singleton, preterm, appropriate for gestational age infants (cases) and 118
      mothers of singleton, term, appropriate for gestational age infants (controls). A
      multiple logistic regression analysis indicated that significant risk factors for
      preterm birth were first or second trimester vaginal bleeding during current
      pregnancy, a previous preterm birth, inadequate prenatal care, consanguinity,
      maternal body mass index of < 23, and short inter-pregnancy interval. Awareness
      of such risk factors is essential in planning public education programs and in
      considering appropriate perinatal care options for women at potentially higher
      risk for preterm delivery.

PMID- 7821498
TI  - Erythrocyte count and indices during normal pregnancy of non-smoking and smoking
      women.
AB  - OBJECTIVE: To compare the erythrocyte count and the erythrocyte indices of
      smoking and non-smoking women at different stages of normal gestation. STUDY
      DESIGN: In 247 non-smoking and 123 smoking healthy pregnant women the erythrocyte
      count and indices were compared at four different stages of pregnancy: 0-10, 10
      20, 21-30 and 31-40 weeks. Exclusion criteria were a diastolic pressure > or = 90
      mmHg, an endocrine disease or a coagulation disorder. A woman was considered a
      smoker if she smoked 4 or more cigarettes/day. Blood samples were run on the
      Sysmex NE-8000. RESULTS: The erythrocyte count was significantly lower in smokers
      than in non-smokers (3.86 T/l versus 3.96 T/l in the last 10 weeks). Comparing
      the erythrocyte count during the beginning and the end of pregnancy there were
      significant lower values in both groups (4.32 T/l to 3.96 T/l in the non-smoking
      and 4.24 T/l to 3.86 T/l in the smoking group). The differences in the median Hb
      and Ht levels were neglectable. The MCV was significantly higher in women who
      smoked, as was the MCH (MCV 91 fl and MCH 1.90 fmol in the non-smoking versus MCV
      94 fl and MCH 1.95 fmol in the smoking group in the last 10 weeks). CONCLUSION:
      Smoking in pregnancy leads to a lower erythrocyte count and a higher MCV which
      might create a hypoxic condition of the fetus.

PMID- 7821499
TI  - Is routine appendectomy beneficial in the management of ovarian cancer?
AB  - A retrospective analysis of 136 patients with ovarian carcinoma subjected to
      appendectomy as a part of surgical procedure was carried out to assess the
      importance of appendectomy in patients with ovarian cancer. Of the 136 patients
      studied, 94 had epithelial and 38 had non-epithelial type of primary ovarian
      carcinoma. In the remaining 4 patients, the primary operation was performed with
      an intraoperative diagnosis of ovarian carcinoma but the final pathological
      examination revealed appendiceal carcinoma metastatic to ovaries. The overall
      appendiceal involvement in the study group with primary ovarian cancer was found
      to be 32.5% (43/132). This figure was 15.7% and 39.3% for non-epithelial and
      epithelial tumors, respectively. Involvement of the appendix ranged from 8.8% for
      patients with stage I disease to 46.0% for patients with stage III-IV disease.
      Four of the appendices found to be inflamed during the surgical explorations were
      later reported as acute appendicitis. The frequent occurrence of metastatic
      disease in the appendix in patients with ovarian cancer suggests routine
      appendectomy is appropriate for staging early cases and for contributing to
      maximal cytoreduction in advanced cases.

PMID- 7821500
TI  - Three cases of sarcoma occurring after radiation therapy of breast cancers.
AB  - We report 3 cases of sarcomas following irradiation for breast carcinoma. Median
      latent period ranged from 7 to 17 years. Histologic types were 1 malignant
      fibrous histiocytoma, 1 osteochondrosarcoma, 1 chondrosarcoma. Diagnosis was
      often delayed because of non-specific clinical features. The prognosis of these
      postirradiation sarcomas was poor with the median survival ranging from 10 to 70
      months. One patient had a complete resection and is alive at 70 months. In the
      other 2 non-resectable patients, chemotherapy and/or radiotherapy did not induce
      an objective response. The poor prognosis when these tumors are diagnosed late
      emphasizes the need for increased awareness, which should lead to earlier
      diagnosis and, it is hoped, permit radical surgical treatment.

PMID- 7821501
TI  - Analysis of menstrual calendars and serum alpha 2-PEG in women on hormone
      replacement therapy for 12 months.
AB  - This study was conducted to assess endometrial protection in women on a cyclical
      combined hormone replacement regimen with 1 mg norethisterone BP, and to evaluate
      the use of the bleeding pattern and serum alpha 2-PEG in monitoring the
      endometrial response to exogenous hormone therapy. Fifty-one postmenopausal women
      attending the Menopause Research Unit at Leicester Royal Infirmary, UK, completed
      the study. All patients were at least 1 year after the menopause, with an average
      of 26 months since the last menstrual period. All women were prescribed a regimen
      of two tablets of Hormonin (oestriol 0.27 mg, oestrone 1.4 mg, and oestradiol 0.6
      mg) continuously, with 1 mg of norethisterone added for 12 days out of each 28
      day treatment cycle. Menstrual diaries were collected and analysed. The secretory
      changes were assessed by histology, menstrual bleeding pattern and a biological
      marker of secretory activity (alpha 2-PEG). Withdrawal bleeding occurred on
      average on days 11, 12, 11, 12 and 13 on months 2, 3, 6, 9 and 12, respectively.
      There was a poor degree of consistency in the bleeding pattern. The level of
      alpha 2-PEG increased from the average baseline measurement of 2.7 ng/ml (S.D.,
      4.12) to 8.5 ng/ml (S.D., 4.16) after progestogen treatment. This rise, although
      significant, did not correlate with the uterine bleeding pattern. There was no
      statistically significant correlation between the level of alpha 2-PEG and
      endometrial histology. The findings highlight the fact that cycle predictability
      on HRT, as exemplified in this regimen, is poor. The level of alpha 2-PEG is a
      poor predictor of the endometrial histology and has a poor correlation with the
      day of onset of bleeding.

PMID- 7821502
TI  - Increased phagocytic activity of polymorphonuclear leukocytes during pregnancy.
AB  - Many immunological parameters are depressed during pregnancy. For this reason, an
      evaluation was made of the phagocytic activity, representing non-specific
      immunity, of polymorphonuclear leukocytes from pregnant women. The cells were
      isolated from heparinized venous human blood of pregnant women of 10 or more
      weeks' gestation and non-pregnant women (controls), 20-30 years old. The results
      indicate that the phagocytosis of inert particles (latex beads) does not
      significantly change in pregnancy. However, the attachment, ingestion and
      digestion of Candida albicans significantly increased in pregnancy, with the
      greatest difference from controls being in the second trimester. These findings
      suggest that the phagocytic activity in pregnant women is enhanced and that this
      increased non-specific immunity may compensate in part for weakened specific
      immunity of the maternal host.

PMID- 7821503
TI  - Excretion of prostacyclin and thromboxane metabolites before, during, and after
      pregnancy-induced hypertension.
AB  - The aim of the present study was to assess whether changes in prostacyclin (PGI2)
      and thromboxane (TXA2) generation precede the manifestation of pregnancy-induced
      hypertension (PH). The metabolites 6-oxo-PGF1 alpha and TXB2 were measured in the
      urine of 69 randomly selected pregnant women from 16-20 weeks of gestation (wg)
      until delivery and more than 6 weeks postpartum. Between 16-20 and 21-24 wg 6-oxo
      PGF1 alpha excretion did not change in patients who later developed PIH (n = 6)
      but increased significantly in the control group (n = 63). In contrast, a marked
      rise in TXB2 excretion was found in the PIH group but not in controls. Thereafter
      significant differences between both groups persisted from 25 wg until delivery.
      The 6-oxo-PGF1 alpha/TXB2 ratio was below the 10th percentile from 21-24 wg until
      delivery in patients with developing PIH. The excretion of both metabolites was
      substantially lower in the non-pregnant state without any difference between
      patient groups. These results show an altered urinary excretion of both 6-oxo
      PGF1 alpha and TXB2 preceding the onset of the disease. A pathophysiological role
      of PGI2 deficiency and increased TXA2 formation in PIH appears substantiated.

PMID- 7821504
TI  - The Dalkon syndrome--a rare condition?
AB  - A patient who presented acutely with severe pelvic sepsis related to Dalkon
      shield is reported. Although the Dalkon syndrome has been described (Tatum HJ,
      Connell EB. Intrauterine contraception. Duvant: Creative Informatics, 1985) the
      term is not widely used and controversy surrounds this condition. However, the
      condition may still present to the modern day gynaecologist.

PMID- 7821505
TI  - Vesicocervical fistula--a rare cause of urinary incontinence.
AB  - A vesicocervical fistula is reported. This extremely rare and late sequela of
      caesarean section, secondary to a lesion in the bladder and unrecognized
      intraoperatively, was followed with a distressing, long-lasting urinary
      incontinence unreactive to conservative treatment. Not until 7 years after the
      primary operation was this lesion diagnosed and treated successfully by vaginal
      approach. Etiological factors, clinical features and treatment possibilities are
      discussed.

PMID- 7821506
TI  - Postpartum ovarian veins thrombophlebitis.
AB  - Puerperal ovarian vein thrombophlebitis (POVT) is a rare postpartal complication.
      Its incidence is about 0.05%. POVT can follow a term pregnancy, a premature
      delivery, an abortion or an ectopic pregnancy. POVT usually presents as a
      syndrome consisting in lower abdominal pain and fever which does not respond to
      adequate antibiotics. We present a case report, in which the diagnosis was based
      upon computed tomography.

PMID- 7821507
TI  - Are multiple cesarean sections safe?
AB  - To assess the maternal and neonatal risk associated with high-order cesarean
      sections, a case-control study was carried out in two university affiliated
      maternity wards. The outcome of 154 pregnancies of women undergoing cesarean
      section for the 4th time or more was compared with 148 women sectioned for the
      2nd or 3rd time and 132 women of similar age and parity after spontaneous birth.
      The main outcome measures were maternal operative and postoperative morbidity and
      neonatal prematurity and its complications, Apgar scores, and the need for
      intensive care. Women undergoing multiple (> or = 4) cesarean sections had
      significantly more intra-abdominal adhesions (P < 0.0001) than women sectioned
      for the 2nd or 3rd time. However, the time interval from incision to delivery and
      the total duration of operation were similar. The postoperative course was not
      adversely affected by multiple cesarean sections. A high incidence (16.2%) of
      preterm cesarean deliveries was noted in the study group. This was due to non
      elective repeat cesarean delivery rather than to poor timing of scheduled
      cesarean sections. The significantly increased (P < 0.05) need for neonatal
      intensive care was explained by the higher occurrence of prematurity. Low Apgar
      scores (< or = 7) at 1 and 5 min were significantly (P < 0.01) related to
      multiple cesarean sections, even after controlling for the effect of gestational
      age. We conclude that multiple cesarean sections pose little risk for the mother,
      but may be associated with increased neonatal risk, attributed mainly to preterm
      non-elective cesarean sections.

PMID- 7821508
TI  - The gene encoding human ribosomal protein L27 is developmentally regulated in
      human kidney.

PMID- 7821509
TI  - Sequence analysis of the 5' flanking sequence of ovine lipoprotein lipase (LPL).

PMID- 7821510
TI  - Using differential display in the study of adipocyte differentiation.

PMID- 7821511
TI  - The differentiation of a potential mesenchymal stem cell population within ovine
      bone marrow.

PMID- 7821512
TI  - Metallothionein and heavy metal poisoning.

PMID- 7821513
TI  - Expression of the XCOUP transcription factor in Xenopus laevis.

PMID- 7821514
TI  - Sox gene expression during neuronal development.

PMID- 7821515
TI  - The role of oncogene products in neutrophil apoptosis.

PMID- 7821516
TI  - Human monocyte-conditioned medium inhibits neutrophil apoptosis in vitro.

PMID- 7821517
TI  - Changes in intracellular calcium in neutrophils of newborn infants following
      hypoxic ischaemia at birth.

PMID- 7821518
TI  - The effects of hypoxia and drugs on intracellular calcium in neonatal
      neutrophils.

PMID- 7821519
TI  - Low temperature-induced adaptations in lipid metabolism and physiological
      function in Acanthamoeba castellanii cultures of different ages.

PMID- 7821520
TI  - The effect of thiolactomycin analogues on fatty acid synthesis in peas (Pisum
      sativum cv. Onward).

PMID- 7821521
TI  - The effects of pesticides on lipid synthesis in olive fruits and tissue cultures.

PMID- 7821522
TI  - Plant fatty acid elongation: sensitivity to thiocarbamate herbicides and their
      sulphoxides.

PMID- 7821523
TI  - Characteristics of two forms of acetyl-CoA carboxylase from maize leaves.

PMID- 7821524
TI  - Ontogenic and regional changes in kinetic constants of alpha-methyl-D-glucoside
      transport in chicken small intestine.

PMID- 7821525
TI  - Hexose uptake and intestinal epithelial surface area in low Na+ adapted chickens.

PMID- 7821526
TI  - The effects of age on glucose-6-phosphatase in an animal model of diabetes.

PMID- 7821527
TI  - Cloning and sequencing of the ovine intestinal Na+/glucose transporter (SGLT1).

PMID- 7821528
TI  - Further evidence for the presence of two facilitative glucose transporter
      isoforms in the brush border membrane of the syncytiotrophoblast of the human
      full term placenta.

PMID- 7821529
TI  - Effect of phorbol 12-myristate 13-acetate on hypoxanthine transport in LLC-PK1
      renal epithelia.

PMID- 7821530
TI  - Glucose and amino acid transport in human peripheral lymphocytes.

PMID- 7821531
TI  - Immunolocalization of GLUT1 and GLUT3 glucose transporters in human placenta.

PMID- 7821532
TI  - Rapid chemiluminescent detection of facilitative glucose transporter mRNAs (GLUTs
      1-4) with digoxigenin end-labelled oligonucleotides.

PMID- 7821533
TI  - Occlusion of sodium by the Na/glucose cotransporter.

PMID- 7821534
TI  - Apoptosis is regulated by the rate of glucose transport in an IL-3-dependent
      haemopoietic cell line.

PMID- 7821535
TI  - Production of functional GLUT1 by co-expression of N- and C-terminal half
      molecules in Xenopus oocytes.

PMID- 7821536
TI  - Mutagenesis of the galactose-H+ symporter, GalP, of Escherichia coli.

PMID- 7821537
TI  - The interaction of forskolin with the galactose-H+ transport protein (GalP) of
      Escherichia coli.

PMID- 7821538
TI  - Investigation of interdomain communication in flavocytochrome b2 by generation of
      interspecies hybrid enzymes.

PMID- 7821539
TI  - Flavocytochrome b2: probing domain mobility by introducing disulphide bridges.

PMID- 7821540
TI  - The use of deletion mutants in the hinge region as functional probes of
      flavocytochrome b2.

PMID- 7821541
TI  - Manipulation of the substrate specificity of flavocytochrome b2.

PMID- 7821542
TI  - Further studies on redox-related activation and deactivation of E. coli nitrate
      reductase: a possible physiologically relevant role for the low potential [4Fe
      4S] centres.

PMID- 7821543
TI  - Duodenal ferric reductase: purification and characterisation.

PMID- 7821544
TI  - E.p.r. characterisation of the molybdenum centre of Rhodobacter capsulatus
      dimethylsulphoxide reductase: new signals on reduction with Na2S2O4.

PMID- 7821545
TI  - Storage effects on the ligand binding properties of bovine heart cytochrome c
      oxidase.

PMID- 7821546
TI  - Inhibitors of electron transport in the cytochrome bd complex of Azotobacter
      vinelandii.

PMID- 7821547
TI  - EPR, ENDOR and ESEEM studies on recombinant benzene dioxygenase.

PMID- 7821548
TI  - Phorbol esters, kainate and ischaemia influence protein kinase C alpha, delta and
      zeta in the rabbit retina, in vitro.

PMID- 7821549
TI  - Effects of propofol on cAMP and Ins(1,4,5)P3 formation and [3H]noradrenaline
      uptake and release from SH-SY5Y cells.

PMID- 7821550
TI  - Down-regulation of protein kinase C isoform gene expression in degenerating
      thalamic neurones--lack of induction in reactive glial cells.

PMID- 7821551
TI  - Peptidyl dipeptidase activity in the haemolymph of insects.

PMID- 7821552
TI  - Metabolism of AF1 (KNEFIRF-NH2) in the nematode Ascaris suum.

PMID- 7821553
TI  - Nicotinic acetylcholine receptors in primary cultures of hippocampal neurons:
      pharmacology and Ca++ permeability.

PMID- 7821554
TI  - Nitric oxide effects on polyamine pathways in cultured hepatocytes.

PMID- 7821555
TI  - In vitro NO and N2O inhibition of the branch point enzyme vitamin B12 dependent
      methionine synthase from rat brain synaptosomes.

PMID- 7821556
TI  - DNA methylation in plants: involvement of two different methyltransferases.

PMID- 7821557
TI  - Histone H1- mediated inactivation of methylated templates in vitro.

PMID- 7821558
TI  - Fluorescent substrates for the EcoRV restriction endonuclease.

PMID- 7821559
TI  - Rapid reaction kinetics on the EcoRV restriction endonuclease.

PMID- 7821560
TI  - An Ile-to-Leu mutant of the EcoRV restriction endonuclease that requires Mn2+ as
      catalytic cofactor.

PMID- 7821561
TI  - Purification and characterisation of the SfiI restriction endonuclease.

PMID- 7821562
TI  - Synapsis by Tn3 resolvase: speed and dependence on DNA supercoiling.

PMID- 7821563
TI  - The aspartic proteinase of equine infectious anaemia virus.

PMID- 7821564
TI  - Aspartic proteinases from the human malarial parasite Plasmodium falciparum.

PMID- 7821565
TI  - A rapid assay for lipocortins using a continuous fluorescence displacement assay
      for phospholipase A2.

PMID- 7821566
TI  - A Ca2+/phospholipid dependent protein kinase from suspension cultures of lucerne.

PMID- 7821567
TI  - Heparin-substituted nylon tubing as a model for the study of lipoprotein
      interactions and metabolism.

PMID- 7821568
TI  - Chemical modification of the alginate lyase from Klebsiella pneumoniae.

PMID- 7821569
TI  - Chemical analysis of alginates from mucoid strains of Pseudomonas aeruginosa.

PMID- 7821570
TI  - Electrophoretic analysis of stimulated cat parotid saliva.

PMID- 7821571
TI  - Electrophoresis of human serum proteins following acute myocardial infarction.

PMID- 7821572
TI  - Studies on DNA and protein synthesis inhibitors using cells in culture.

PMID- 7821573
TI  - Characterisation and Ca(2+)-dependency of the soluble and particulate
      Ins(1,4,5)P3 5-phosphatase in bovine tracheal smooth muscle.

PMID- 7821574
TI  - Comparison of the properties of human group II phospholipase A2 with other
      secretory phospholipases.

PMID- 7821575
TI  - The effect of endotoxin on the activity of group II rat liver phospholipase A2.

PMID- 7821576
TI  - Some properties of a human group II phospholipase A2 expressed from a synthetic
      gene in E. coli.

PMID- 7821577
TI  - Studies of dissociation-association processes in clostridial glutamate
      dehydrogenase.

PMID- 7821578
TI  - Steady-state kinetics and transient studies of substrate and coenzyme analogue
      binding to clostridial glutamate dehydrogenase (GDH) during oxidative
      deamination.

PMID- 7821579
TI  - The changed pattern of substrate specificity in the K89L mutant of glutamate
      dehydrogenase of Clostridium symbiosum.

PMID- 7821580
TI  - Venturicidin titrates a redox cofactor of mitochondrial ATP synthase.

PMID- 7821581
TI  - Hypothesis: a controlled chaotic attractor constitutes the central oscillator of
      the circadian clock.

PMID- 7821583
TI  - Membrane potential studies of Saccharomyces cerevisiae during cider fermentation.

PMID- 7821582
TI  - Hydrogenosomes in trichomonads are calcium stores and have a transmembrane
      electrochemical potential.

PMID- 7821584
TI  - Neutrophil activation and priming during engagement of CD11b/CD18 integrins.

PMID- 7821585
TI  - In vivo cytotoxic effects of antisera raised to individual polypeptide components
      of ovine adipocyte plasma membranes in Clun lambs.

PMID- 7821586
TI  - The interaction of positively charged phospholipid vesicles with bacteria.

PMID- 7821587
TI  - A theoretical approach to polyhydroxy-mediated interactions between liposomes and
      bacterial biofilms.

PMID- 7821588
TI  - Dinitrogenase reductase ADP-ribosyl transferase and dinitrogenase reductase
      activating glycohydrolase in Gloeothece.

PMID- 7821589
TI  - Cellular proteins associated with the E5 oncoprotein of human papillomavirus type
      16.

PMID- 7821590
TI  - Analysis of the physical state of human papillomavirus type-16 in early cervical
      intraepithelial neoplasia.

PMID- 7821591
TI  - Detection of protein aggregates, but not virus-like particles, when the major
      (L1) coat protein of a wild-type human papillomavirus type 16 (HPV-16) is
      expressed in insect cells.

PMID- 7821592
TI  - Expression of human papillomavirus type 16 (HPV-16) major (L1) and minor (L2)
      capsid proteins in insect cells as polyhistidine fusion proteins.

PMID- 7821593
TI  - Comparison of capsid-associated RNA-dependent RNA polymerase activity of double
      stranded RNA virus-like particles from different yeast genera.

PMID- 7821594
TI  - Effect of essential fatty acid deficiency & immunopathological stresses on blood
      brain barrier (B-BB) in Lewis rats: a biochemical study.

PMID- 7821595
TI  - Effect of dietary cholesterol on membrane properties and immune functions in
      rainbow trout.

PMID- 7821596
TI  - Species differences in the circulating pool of lipoprotein lipase.

PMID- 7821597
TI  - Homocysteine induced endothelial cell toxicity and its protection.

PMID- 7821598
TI  - A rat vein perfusion model for studying homocysteine induced toxicity.

PMID- 7821599
TI  - Insulin-like growth factor binding proteins in serum and tissue in hypertension.

PMID- 7821600
TI  - The acute effects of inflammation upon protein synthesis rates in spontaneously
      hypertensive rats.

PMID- 7821601
TI  - Effects of angiotensin converting enzyme inhibition on cardiac collagen in
      hypertensive and normotensive rats.

PMID- 7821602
TI  - A hyperresponsive 15-lipoxygenase phenotype in rabbit and human populations:
      relationship to atherosclerosis.

PMID- 7821603
TI  - Atrophic changes in skeletal muscle due to osmotic diarrhoea.

PMID- 7821604
TI  - Variable responses of chronic ethanol feeding on protein metabolism in different
      regions of the gastrointestinal tract.

PMID- 7821605
TI  - Tumour necrosis factor, interleukin-6 and growth hormone binding protein in acute
      and chronic experimental ethanol toxicity.

PMID- 7821606
TI  - The effect of chronic alcohol administration upon cardiac nucleotide
      concentrations and histomorphometry.

PMID- 7821607
TI  - Identification of differentially expressed genes during the progression of
      diabetic nephropathy.

PMID- 7821608
TI  - An investigation of the role of atrial natriuretic factor in the development of
      diabetic nephropathy.

PMID- 7821609
TI  - Molecular analysis of a candidate developmentally regulated gene from human fetal
      kidney.

PMID- 7821610
TI  - Partial sequence of the GDP-mannose dehydrogenase gene from Azotobacter
      vinelandii.

PMID- 7821611
TI  - The two ccaat-enhancer binding protein isoforms, IL-6DBP and C/EBP delta, are
      induced by interleukin-6 to promote gene transcription in hepatocytes via
      different mechanisms.

PMID- 7821612
TI  - Lurching, reeling, waddling and staggering in mice--is carbonic anhydrase (CA)
      VIII a candidate gene?

PMID- 7821613
TI  - A molecular phylogeny of the British species of Callithamnion based on
      restriction site data.

PMID- 7821614
TI  - A comparison of calcium channel currents in vascular smooth muscle cells from
      Watanabe hereditary hypercholesterolaemic and New Zealand white rabbits.

PMID- 7821615
TI  - Galactose residues in Plasmodium falciparum glycoproteins: incorporation and
      elimination.

PMID- 7821616
TI  - Sialyltransferases of the bonnet monkey cervical epithelium: isolation and
      characterization.

PMID- 7821617
TI  - Interaction of a peptide corresponding to the amino terminus region of the S
      protein of hepatitis B virus with liposomes.

PMID- 7821618
TI  - Ionic dependence of the sialidase activity of hemagglutinin-neuraminidase
      glycoprotein in Newcastle disease virus membrane.

PMID- 7821619
TI  - The nature of thermal transitions in purple membranes from Halobacterium
      halobium.

PMID- 7821621
TI  - Determination of membrane fluidity: a comparison of biophysical methods.

PMID- 7821620
TI  - Comparative differential scanning calorimetry study of erythrocyte ghosts from
      different mammalian species.

PMID- 7821622
TI  - Surfactant protein-C enhances lipid aggregation activity of surfactant protein-A.

PMID- 7821623
TI  - ESR and ENDOR characterization of flavodoxin from Anabaena sp. PCC 7119.

PMID- 7821624
TI  - Deacylated pulmonary surfactant protein SP-C has different effects on the
      thermotropic behaviour of bilayers of dipalmitoylphosphatidyl-glycerol (DPPG)
      than the native acylated protein.

PMID- 7821625
TI  - Reconstitution of rat liver gap junctions into liposomes.

PMID- 7821626
TI  - Activation of phospholipase A2 by TNF alpha in transformed and non transformed
      fibroblasts.

PMID- 7821627
TI  - Alterations in membrane permeability is an early event in the cytotoxic effect of
      TNF alpha.

PMID- 7821628
TI  - X-ray diffraction studies of the mixed dispersion of dioleoyl-derivatives of
      phosphatidylcholine and phosphatidyl-ethanolamine in aqueous-dimethylsulphoxide.

PMID- 7821629
TI  - Differences between basolateral and apical plasma membrane enriched fractions
      from parietal cells: presence of P2y receptors.

PMID- 7821630
TI  - Effect of sorbitol on the phase transition temperatures of
      dipalmitoylphosphatidilcholine.

PMID- 7821631
TI  - Thermal stability of photosystem II of Arabidopsis mutants deficient in fatty
      acid desaturation.

PMID- 7821632
TI  - Probing protein conformation by infrared spectroscopy.

PMID- 7821633
TI  - Chemical modification of Ca(2+)-ATPase from sarcoplasmic reticulum with
      phenylglyoxal.

PMID- 7821635
TI  - Differential scanning calorimetry study of the thermal unfolding of sarcoplasmic
      reticulum Ca2+, Mg(2+)-ATPase from rabbit skeletal muscle.

PMID- 7821634
TI  - Time-resolved phosphorescence anisotropy as a tool to study the conformation and
      oligomeric structure of ion-transport ATPases.

PMID- 7821636
TI  - Direct targets of homeotic gene control in Drosophila.

PMID- 7821637
TI  - Mechanisms of heritable gene silencing during Drosophila development.

PMID- 7821638
TI  - Molecular basis of limb development.

PMID- 7821639
TI  - Sonic hedgehog: a key mediator of anterior-posterior patterning of the limb and
      dorso-ventral patterning of axial embryonic structures.
AB  - Sonic hedgehog is expressed in several sites during embryogenesis which are known
      to be important in directing the development of neighbouring tissues, including
      Hensen's node, the notochord, the floor plate of the neural tube, and the
      posterior of the limb bud. A unity in signalling mechanisms utilized by these
      inducers was first indicated because they all can provide a source of limb
      polarizing activity, assayed by grafting into the anterior of a limb bud. The
      hypothesis that they share a common signal is substantiated by the fact that they
      all express Sonic. Moreover, ectopic expression of Sonic in vivo suggests that it
      is responsible for the polarizing activity of the ZPA and plays an important role
      in dorso-ventral patterning of the spinal cord. The isolation of Sonic heralds a
      new era in the investigation of the molecular mechanisms of these key inductive
      interactions in vertebrate development.

PMID- 7821640
TI  - The expression of retinoic acid receptors in Xenopus development.

PMID- 7821641
TI  - Complex regulation of Xenopus HoxAI and HoxDI.

PMID- 7821642
TI  - The role of fibroblast growth factors in early Xenopus development.

PMID- 7821643
TI  - Genes and apoptosis.

PMID- 7821644
TI  - The role of protein kinase C in myeloid cell apoptosis.

PMID- 7821645
TI  - Mechanisms of programmed cell death and Bcl-2 protection.

PMID- 7821646
TI  - A tumour-derived immunosuppressive factor induces apoptosis: evidence for in
      vitro and in vivo activity.

PMID- 7821647
TI  - The regulation of apoptosis in thymocytes.

PMID- 7821648
TI  - Surfactant--pesticide--plant interactions.

PMID- 7821649
TI  - Herbicides inhibiting acetyl-CoA carboxylase.

PMID- 7821650
TI  - Thiocarbamates and surface lipid synthesis.

PMID- 7821651
TI  - Carotenoid biosynthesis: a target site for bleaching herbicides.

PMID- 7821652
TI  - The effects of antifungal compounds on growth and sterol metabolism in plants and
      protozoa.

PMID- 7821653
TI  - Steroid metabolism as a target for insect control.

PMID- 7821654
TI  - The variability of kinetic parameters for sugar transport in different mutants of
      the galactose-H+ symport protein, GalP, of Escherichia coli.

PMID- 7821655
TI  - Mechanisms of Na(+)-glucose cotransport.

PMID- 7821656
TI  - The pre-steady-state kinetics of conformational changes in sugar transporters.

PMID- 7821657
TI  - Dietary regulation of the intestinal sodium-dependent glucose cotransporter
      (SGLT1).

PMID- 7821658
TI  - Hepatic microsomal glucose transport.

PMID- 7821660
TI  - Targeting of the insulin-regulatable glucose transporter (GLUT-4).

PMID- 7821659
TI  - Mammalian glucose transporters: intracellular signalling and transporter
      translocation.

PMID- 7821661
TI  - Glucose transporters in mammalian brain.

PMID- 7821662
TI  - Insulin signalling and the stimulation of glucose transport.

PMID- 7821663
TI  - Expression of the hexose transporters GLUT1-GLUT5 and SGLT1 in clones of Caco-2
      cells.

PMID- 7821664
TI  - Regulated expression of GLUT2 in diabetes studied in transplanted pancreatic beta
      cells.
AB  - GLUT2 disappearance is a marker of the beta cell glucose-unresponsiveness
      associated with diabetes. Understanding the factor(s) leading to this dysfunction
      may shed light on pathogenesis of diabetes. Since the regulation of GLUT2
      expression in diabetes can so far only be studied in in vivo experiments, we
      developed a novel experimental approach to study the genetic regulation of GLUT2
      in diabetes. By encapsulating islets or cell lines in semi-permeable membranes,
      these cells can be exposed to the diabetic environment of rats or mice and can be
      retrieved for analysis of GLUT2 expression and for the change in the secretory
      response to glucose. Immunocytochemical analysis of transporter expression
      reveals changes in protein expression while transcriptional analysis of GLUT2
      gene expression could be performed in cells transfected with promoter-reporter
      gene constructs. Using this last approach we hope to be able to characterize the
      promoter regions involved in the beta cell- and diabetes-specific regulation of
      GLUT2 expression and possibly to determine which factors are responsible for this
      regulation.

PMID- 7821665
TI  - Design and synthesis of simplified energy-converting proteins.

PMID- 7821666
TI  - The tetrahaem cytochromes associated with photosynthetic reaction centres: a
      model system for intraprotein redox centre interactions.

PMID- 7821667
TI  - Variations on a theme of Fe-O-Fe proteins.

PMID- 7821668
TI  - The binding of cyanide and carbon monoxide to bacterial cytochrome bo.

PMID- 7821669
TI  - Haem, flavin and oxygen interactions in Hmp, a flavohaemoglobin from Escherichia
      coli.

PMID- 7821671
TI  - Metal-redox centre interactions in photosynthetic reaction centres.

PMID- 7821670
TI  - Flavin to haem electron transfer in flavocytochrome b2.

PMID- 7821672
TI  - Long-distance spin-spin interactions with iron-sulphur clusters as observed by
      e.p.r. spectroscopy.

PMID- 7821673
TI  - Electron transfer reactions of cellobiose oxidase.

PMID- 7821674
TI  - Inhibitory mechanisms and clinical applications of anticholinesterases.

PMID- 7821675
TI  - Multi-level regulation of acetylcholinesterase biosynthesis and maturation.

PMID- 7821676
TI  - Expression and ligand specificity of acetylcholinesterase and the nicotinic
      receptor: a tale of two cholinergic sites.
AB  - The functional design of the nAChR and AChE rather than their recognition
      capacities requires divergence in structure of the two binding sites. The
      receptor requires co-operativity to link ligand occupation to the response, rapid
      conformational transitions of activation, and slower transitions of
      desensitization. Hence, its binding sites have evolved at subunit interfaces. By
      contrast, AChE functions with a large kcat and a comparatively large Km. To do
      so, it must force acetylcholine through a low-energy transition site that
      features tetrahedral rather than the ground-state, trigonal conformation around
      the carbonyl carbon. This requires a high affinity (KD approximately 10(-17) M)
      for the enzyme complex of the transient transition state. Interestingly, the
      three-finger peptide toxins (alpha-bungarotoxin and fasciculin), though closely
      homologous, use different interaction sites on the receptor (the agonist
      recognition site) and AChE (a peripheral site). Finally, although the two
      proteins show co-ordinated expression during muscle differentiation, the receptor
      relies primarily on transcriptional control while AChE expression is post
      transcriptional, being controlled by mRNA stability.

PMID- 7821677
TI  - Three-dimensional structures of acetylcholinesterase and of its complexes with
      anticholinesterase agents.

PMID- 7821678
TI  - Non-cholinergic functions of acetylcholinesterase.

PMID- 7821679
TI  - A novel acetylcholinesterase inhibitor, Ro 46-5934, which interacts with
      muscarinic M2 receptors.

PMID- 7821680
TI  - Trimethylsilylated trifluoromethyl ketones, a novel class of acetylcholinesterase
      inhibitors: biochemical and pharmacological profile of MDL 73,745.

PMID- 7821681
TI  - Monoamine oxidase inhibition.

PMID- 7821682
TI  - Biochemical and pharmacological evaluation of 2,4
      difluorobenzyldimethylsilylmethanamine, a new highly selective inhibitor of
      monoamine oxidase-B.

PMID- 7821683
TI  - Role of cholesterol as a structural and functional effector of the nicotinic
      acetylcholine receptor.

PMID- 7821684
TI  - New insights into the structure of cell membranes from single particle tracking
      experiments.

PMID- 7821685
TI  - Fluorescence energy transfer as a tool to locate functional sites in membrane
      proteins.

PMID- 7821686
TI  - Assembly of gap junction intercellular communication channels.

PMID- 7821687
TI  - Phosphorylated and non-phosphorylated connexin-32 molecules in gap junction
      plaques are protected against calpain proteolysis after phosphorylation by
      protein kinase C.

PMID- 7821688
TI  - Protein engineering for the elucidation of the mechanism of electron transfer in
      redox proteins.

PMID- 7821689
TI  - High-resolution, non-crystallographic structural studies of large integral
      membrane proteins.
AB  - The work described here clearly demonstrates that n.m.r. is a viable method with
      which to resolve molecular details about membrane proteins and can give
      information at a resolution comparable with that gained from crystallographic
      studies, where, in the limited number of cases studied so far, such information
      is available. Sensitivity is not a major problem although other difficulties may
      prevent particular kinds of information being resolved. However, because bond
      orientational details are obtained ab initio, the method is quite model
      independent and interpretationally unique. The requirements for solid-state
      n.m.r. methods to be applied to a large membrane protein are that: a sufficient
      amount of functionally active protein is available; the protein should be located
      in bilayers; and suitable specific isotopic enrichment is achieved, in ideal
      cases, either by chemical or biosynthetic means. Achieving these requirements
      will need to draw on a range of skills, possibly genetic or chemical or both, and
      a full understanding of the biochemistry is essential to ensure that any
      structural information gained is functionally relevant. The structural
      information potentially available includes: (a) conformation details about
      specific parts of a protein or its binding sites; (b) distance measurements
      between specific labels introduced into the protein; (c) dynamics of particular
      parts of the protein; (d) chain folding and residue orientation; and (e) the
      mechanistic changes that can occur during a functional cycle. Much developmental
      work still needs to be done both on the sample handling instrumental side and
      with the theoretical aspect of the method.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7821690
TI  - Structure and function of the proton-conducting sector of the vacuolar H(+)
      ATPase.

PMID- 7821691
TI  - Agonist-induced Ca2+ influx in human neutrophils is not mediated by production of
      inositol polyphosphates but by emptying of the intracellular Ca2+ stores.

PMID- 7821693
TI  - Molecular cloning and functional expression of potassium channels from the
      adrenal medulla.

PMID- 7821692
TI  - Regulation of the glucose transporter GLUT1 in mammalian cells.

PMID- 7821694
TI  - Lipid-protein interactions and Ca(2+)-ATPase function.

PMID- 7821695
TI  - Structural aspects of the Ca(2+)-ATPase from sarcoplasmic reticulum.

PMID- 7821696
TI  - Conformational transitions in the function of cation transport ATPases.

PMID- 7821697
TI  - Phospholipase-C-promoted liposome fusion.

PMID- 7821698
TI  - Inhibition of ecdysone biosynthesis in flies by a hexapeptide isolated from
      vitellogenic ovaries.
AB  - The only identified insect peptides known to be involved in controlling the
      biosynthesis of ecdysone, the steroid moulting hormone of arthropods, are the
      prothoracicotropic hormones (PTTH). These neuropeptides stimulate ecdysone
      biosynthesis. Recently, a hexapeptide (NPTNLH) with folliculostatic and trypsin
      modulating activity was isolated from vitellogenic ovaries of the fleshfly
      Neobellieria bullata. Here we report that the hexapeptide, when tested in vitro
      on the isolated ring gland of flies, inhibited ecdysone biosynthesis immediately
      and completely (EC50 = 5 nM). The hexapeptide is the first known factor with
      'prothoracicostatic activity' and may form part of the endocrine system that
      controls ecdysone biosynthesis in vivo.

PMID- 7821699
TI  - Topography of the Leydig cell mitochondrial peripheral-type benzodiazepine
      receptor.
AB  - Native MA-10 mouse Leydig tumor cell mitochondrial preparations were examined by
      transmission electron (TEM) and atomic force (AFM) microscopic procedures in
      order to investigate the topography and organization of the peripheral-type
      benzodiazepine receptor (PBR). Mitochondria were immunolabeled with an anti-PBR
      antiserum coupled to gold-labeled secondary antibodies. Results obtained indicate
      that the 18,000 MW PBR protein is organized in clusters of 4-6 molecules.
      Moreover, on many occasions, the interrelationship among the PBR molecules was
      found to favor the formation of a single pore. Taking into account recent
      observations that the 18,000 MW PBR protein is functionally associated with the
      pore forming 34,000 MW voltage-dependent anion channel (VDAC) these results
      suggest that (i) the mitochondrial PBR complex could function as a pore, thus
      allowing the translocation of cholesterol and other molecules to the inner
      mitochondrial membrane, and (ii) the native receptor is a multimeric complex of
      an approximate 140,000 MW composed on an average of five 18,000 PBR subunits, one
      34,000 VDAC subunit, and associated lipids.

PMID- 7821700
TI  - Characterization of 17 beta-hydroxysteroid dehydrogenase type 1 in
      choriocarcinoma cells: regulation by basic fibroblast growth factor.
AB  - 17 beta-Hydroxysteroid dehydrogenase type 1 (17-HSD type 1) is a steroidogenic
      enzyme catalyzing reversible interconversion of estradiol and estrone. 17-HSD
      type 1 is actively expressed in human placenta. We characterized 17-HSD type 1
      expression and its regulation by basic fibroblast growth factor (bFGF) in JAR,
      JEG-3 and BeWo choriocarcinoma cell lines. Based on Southern and Northern
      analysis, as well as measurement of catalytic activity and immunoreactive
      protein, all the choriocarcinoma cell lines contained and expressed the gene
      coding for 17-HSD type 1, identical to that of normal human cells. However, the
      cell lines showed marked quantitative differences in the levels of expression of
      the enzyme, being lowest in JAR cells and highest in BeWo cells, as measured by
      immunofluorometric assay, Northern analysis and catalytic activity. These
      differences in the basal level of expression were most probably not based on any
      sequence differences in the putative proximal promoter area of the gene in
      different cell lines, since no dissimilarities were observed in the 806 bp region
      upstream from the transcription start site of 1.3 kb mRNA coding for 17-HSD type
      1 except for frequent polymorphism characteristic of normal human cells using
      polymerase chain reaction/single-strand conformation polymorphism (PCR-SSCP)
      analysis. The reductive (estrone-->estradiol) activity was about 4-7 times higher
      compared with the oxidative activity (estradiol-->estrone) in all the cell lines
      studied, indicating that in these choriocarcinoma cell lines, 17-HSD activity
      favours estradiol formation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7821701
TI  - Widespread tissue distribution of steroid sulfatase, 3 beta-hydroxysteroid
      dehydrogenase/delta 5-delta 4 isomerase (3 beta-HSD), 17 beta-HSD 5 alpha
      reductase and aromatase activities in the rhesus monkey.
AB  - Dehydroepiandrosterone-sulfate (DHEA-S), the main secretory product of the human
      adrenal, requires the presence of steroid sulfatase, 3 beta-hydroxysteroid
      dehydrogenase/delta 5-delta 4 isomerase (3 beta-HSD), 17 beta-hydroxysteroid
      dehydrogenase (17 beta-HSD), 5 alpha-reductase, and aromatase to form the active
      androgen dihydrotestosterone (DHT) and the estrogens 17 beta-estradiol (E2) and 5
      androst-ene-3 beta,17 beta-diol (delta 5-diol) in peripheral target tissues.
      Because humans, along with non-human primates are unique in having adrenals that
      secrete large amounts of DHEA-S, the present study investigated the tissue
      distribution of the enzymatic activity of the above-mentioned steroidogenic
      enzymes required for the formation of active sex steroids in the male and female
      rhesus monkey. Estrone and DHEA sulfatase activities were measured in all 25
      tissues examined, and with the exception of the salivary glands, estrogenic and
      androgenic 17 beta-HSDs were present in all the tissues examined. The adrenal,
      small and large intestine, kidney, liver, lung, fat, testis, prostate, seminal
      vesicle, ovary, myometrium, and endometrium all possess the above-mentioned
      enzymatic activities, thus suggesting that these tissues could possibly form the
      biologically active steroids E2 and DHT from the adrenal precursor DHEA-S. On the
      other hand, the oviduct, cervix, mammary gland, heart, and skeletal muscle
      possess all the enzymatic activities required to synthesize E2 from DHEA-S. The
      present study describes the widespread tissue distribution of steroid sulfatase,
      3 beta-HSD, 17 beta-HSD, 5 alpha-reductase, and aromatase activities in rhesus
      monkey peripheral tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7821702
TI  - Long-term co-culture of bovine granulosa cells with microvascular endothelial
      cells: effect on cell growth and cell death.
AB  - The intraovarian axis between granulosa cells and thecal cells is regulated by
      locally produced autocrine and paracrine factors. Until now, microvascular
      endothelial cells (MVEC) have not been included in such studies. Bovine granulosa
      cells from medium-sized antral follicles were plated at low density into the
      lower compartment of 24-well-culture plates on day 0. MVEC derived from bovine
      corpus luteum were seeded on appropriate inserts and placed as the upper
      compartment on day 1. Control granulosa cell cultures and MVEC co-cultures were
      maintained in serum-containing medium. On day 21, control cultures displayed an
      epithelioid monolayer and the coculture displayed a multilayer. Histochemical
      staining for 3 beta-HSD activity and for the lipid droplet stain with the
      fluorescent dye Nile Red were strong, suggesting augmented steroidogenesis in the
      multilayer. Yet the progesterone levels of supernants corrected for 10,000 cells
      were similar in monolayers and in multilayers. Co-cultures contained
      approximately three times more granulosa cells than control cultures as evaluated
      with a Coulter counter. Additionally, the occurrence of dead cells was quantified
      with the fluorescent DNA stain, ethidium homodimer, in 11-day-old control
      cultures and MVEC co-cultures which were deprived of serum, MVEC, or both for an
      additional 40 h. Serum and MVEC suppressed the occurrence of granulosa cell
      death. It is concluded that MVEC produce survival factors for the growth and
      maintenance of granulosa cells.

PMID- 7821703
TI  - The effects of gonadotropin on the phosphatidylinositol pathway in the primate
      corpus luteum.
AB  - The current study was designed to investigate the effects of gonadotropin on
      basal and prostaglandin (PG) F2 alpha-induced activity of the
      phosphatidylinositol pathway in corpora lutea (CL) of rhesus monkeys. Luteal
      progesterone production in vitro was significantly stimulated (P < 0.05) by human
      chorionic gonadotropin (hCG). Neither basal nor PGF2 alpha-induced
      phosphatidylinositol 4,5-bisphosphate hydrolysis was significantly influenced by
      hCG in CL of various ages (P > 0.10). Gonadotropin did induce a slight, yet
      sustained, increase (P < 0.05) in [Ca2+]i in approximately 70% of luteal cells.
      The maximal increase in [Ca2+]i in response to hCG (approximately 100 nM) was
      about one-tenth that induced by PGF2 alpha (approximately 1000 nM). hCG treatment
      did not alter (P > 0.10) the increase in [Ca2+]i induced by PGF2 alpha Treatment
      induced changes in [Ca2+]i did not differ between small (17-21 microns) and large
      (23-28 microns) luteal cells. Therefore, luteolytic agents are more potent
      activators of the phosphatidylinositol pathway than luteotropins. This is
      consistent with the hypothesis that the phosphatidylinositol pathway is involved
      in primate luteal regression. The inability of hCG to acutely alter the
      responsiveness of this pathway to PGF2 alpha suggests that CG may rescue the CL
      of early pregnancy via a mechanism other than direct inhibition of the luteolytic
      actions of PGF2 alpha.

PMID- 7821704
TI  - Functional expression of a stably transfected parathyroid hormone/parathyroid
      hormone related protein receptor complementary DNA in CHO cells.
AB  - Chinese hamster ovary (CHO) cells were stably transfected with OK-O complementary
      DNA encoding the parathyroid hormone/parathyroid hormone related protein
      (PTH/PTHrP) receptor derived from opossum kidney (OK) cells (Juppner et al.,
      1991). A subclone of transfected CHO cells, CHO-E2, presented high affinity
      binding of 125I-labeled [Tyr36]chickenPTHrP(1-36)amide ([125I]chPTHrP(1-36)) (Kd
      1.28 +/- 0.10 nM) similar to that of wildtype OK cells (Kd 2.23 +/- 0.16 nM) (P <
      0.01). Photoaffinity labeling of the PTH/PTHrP receptors using N
      hydroxysuccinimidyl-4-azidobenzoate modified [125I]chPTHrP(1-36) revealed the
      same specifically labeled 90 kDa protein in CHO-E2 and OK cells. In CHO-cells,
      chPTHrP(1-36) stimulated cyclic AMP accumulation in dose-dependent fashion (EC50
      0.15 +/- 0.04 nM) and raised peak cytosolic free calcium concentration (EC50 2.90
      +/- 0.36 nM) independent of extracellular calcium, and stimulated phosphate
      uptake (EC50 0.21 +/- 0.07 nM). Both, chPTHrP(1-36) and 12-O-tetradecanoylphorbol
      13-acetate stimulated phosphate uptake were suppressed by staurosporine. But, Sp
      cyclic adenosine-3',5'-monophosphothioate did not affect phosphate uptake in CHO
      E2 cells. In conclusion, a PTH/PTHrP receptor stably expressed in CHO cells is
      linked to stimulation of phosphate uptake. Receptor coupling presumably occurred
      through the protein kinase C rather than the protein kinase A pathway.

PMID- 7821705
TI  - Glucocorticoid and phorbol ester effects in 3T3-L1 fibroblasts suggest multiple
      and previously undescribed mechanisms of glucocorticoid receptor-AP-1
      interaction.
AB  - A number of mechanisms have been proposed to account for glucocorticoid hormone
      and mitogen effects observed on the transcription of engineered exogenous target
      genes. However, the effect of the co-addition of these agents on the full range
      of endogenous responsive genes in a given cell type has not been addressed. We
      detected 19 metabolically labeled proteins or in vitro translation products whose
      synthesis was altered in 3T3-L1 fibroblasts in response to glucocorticoid hormone
      using two-dimensional electrophoresis on large-format gels. Co-addition of the
      mitogenic phorbol ester, tetradecanoylphorbolacetate (TPA), with glucocorticoid
      hormone resulted in independent (one species), synergistic (six species), and
      antagonistic (five species) effects on the glucocorticoid regulation of
      individual gene products, while seven other glucocorticoid regulated species were
      not affected. These and additional observations suggest direct and gene-specific
      effects of glucocorticoid receptor and AP-1 on the transcription of responsive
      genes, and for some of these genes the pattern of regulation is not accounted for
      by mechanisms described to date. In addition, the pattern of regulation of five
      species is consistent with a role in mediating the opposing physiological effects
      of glucocorticoid hormone and growth factors in these cells.

PMID- 7821706
TI  - Inhibition of estrogen-induced progesterone receptor in MCF-7 human breast cancer
      cells by aryl hydrocarbon (Ah) receptor agonists.
AB  - 17 beta-Estradiol (E2) induces progesterone receptor (PR) binding, immunoreactive
      protein, nuclear PR formation and PR mRNA levels in MCF-7 human breast cancer
      cells. Gel mobility shift analysis of nuclear extracts from E2-treated cells also
      exhibited a higher intensity retarded band associated with formation of a PR
      complex with a consensus [32P]progesterone/glucocorticoid responsive element. In
      contrast, 1 nM 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alone did not alter or
      decrease these same responses in MCF-7 cells; however, in cells co-treated with 1
      nM TCDD plus 1 nM E2, TCDD significantly inhibited all the E2-induced responses.
      Scatchard analysis of PR binding demonstrated that TCDD decreased the number of
      E2-induced PR cellular binding sites but not the binding affinity of the PR for a
      radiolabeled promegestrone. In parallel studies, 3-methylcholanthrene, a
      prototypical polynuclear aromatic hydrocarbon, also inhibited E2-induced PR
      binding and immunoreactive protein. For a series of halogenated aromatics
      including 2,3,7,8- and 1,2,7,8-tetrachlorodibenzofuran, 1,3,7,8-TCDD and 6-methyl
      1,3,8-trichlorodibenzofuran, their rank order potency for inhibiting E2-induced
      PR binding paralleled their rank order binding to the aryl hydrocarbon (Ah)
      receptor. These results support a role for the Ah receptor in mediating the
      antiestrogenic activity of polynuclear and halogenated aromatic hydrocarbons and
      illustrate cross-talk between the Ah and estrogen receptor signal transduction
      pathways.

PMID- 7821707
TI  - Developmental regulation of Sertoli cell lactate production by hormones and the
      testicular paracrine factor, PModS.
AB  - Testicular peritubular cells produce a paracrine factor termed PModS that
      mediates mesenchymal-epithelial interactions and modulates Sertoli cell functions
      essential for the process of spermatogenesis. Sertoli cells produce lactate as a
      preferred energy metabolite for developing spermatogenic cells. The current study
      was designed to examine the actions of PModS and hormones on Sertoli cell lactate
      production at various stages of pubertal development. Sertoli cells were isolated
      from pre-pubertal (10 day), mid-pubertal (20 day) and late pubertal (35 day) rat
      testes. Lactate accumulation in the conditioned-medium of cultured Sertoli cells
      was measured. Basal lactate production increased approximately fivefold during
      pubertal Sertoli cell development. Therefore, lactate production increases as the
      Sertoli cell differentiates during pubertal development. The ability of
      regulatory agents such as FSH or a combination of FSH, insulin, retinol and
      testosterone (FIRT) to stimulate lactate production decreased during pubertal
      development as Sertoli cell differentiation increased. Purified PModS stimulated
      lactate production in Sertoli cell preparations throughout pubertal development.
      PModS had a greater effect than FSH in stimulating late pubertal Sertoli cell
      lactate production. PModS in combination with FIRT resulted in an additive
      stimulation of lactate production suggesting a distinct mechanism of action for
      PModS. Observations support the proposal that the locally produced paracrine
      factor PModS mediates mesenchymal-epithelial cell interactions during pubertal
      development and that these interactions promote Sertoli cell differentiated
      functions (i.e. lactate production) required for the developing spermatogenic
      cells.

PMID- 7821708
TI  - Differential gene expression of fibroblast growth factor receptor isoforms in rat
      ovary.
AB  - The gene expression of four fibroblast growth factor receptors (flg, bek, FGFR-3,
      and FGFR-4) in rat ovary cells was studied. Northern blot hybridization revealed
      that flg and bek mRNAs were detectable during all stages except a diestrus stage,
      whereas FGFR-3 and FGFR-4 mRNAs were almost undetectable throughout the cycles.
      In situ hybridization also demonstrated that only flg and bek gene expression was
      detectable. A modest flg mRNA signal was detected in developing antral follicles
      and it was more prominent in the theca-interstitial cells than in the granulosa
      cells. A modest to weak flg mRNA signal was seen in the hypertrophied theca
      interstitial cells of atretic follicles and a very weak flg mRNA signal was
      observed in the corpora lutea. On the other hand, a weak bek mRNA signal was seen
      in granulosa and theca-interstitial cells in developing follicles and also
      hypertrophied theca-interstitial cells of atretic follicles, but not in the
      corpora lutea. Intense signals for both flg and bek mRNAs were unexpectedly found
      in the epithelium of paroophoron at the hilus. These results demonstrate that the
      bFGF receptor isoforms are expressed differentially in the rat ovary cells.

PMID- 7821709
TI  - Overexpression of rainbow trout estrogen receptor domains in Escherichia coli:
      characterization and utilization in the production of antibodies for
      immunoblotting and immunocytochemistry.
AB  - Complementary DNA fragments that encode central and C-terminal domains of rainbow
      trout estrogen receptor (rtER) were expressed in Escherichia coli as fusion
      proteins with glutathione-S-transferase (GST). Both fusion proteins were induced
      by IPTG and could readily be detected as a 53-55 kDa band in crude extracts or in
      insoluble fraction after polyacrylamide gel electrophoresis and Coomassie blue
      staining. These recombinant proteins were solubilized and partially purified (ca.
      60-75%) using centrifugation and different concentrations of urea. Gel mobility
      shift assays revealed that the hybrid protein containing ER central domain forms
      a specific complex with a synthetic estrogen-response-element. Similarly, we
      showed by steroid-binding assays that the hybrid protein containing the ER C
      terminal domain binds specifically estrogen and not other steroids. These hybrid
      receptors were further isolated by electroelution after electrophoresis and used
      to immunize rabbits. Polyclonal antibodies from each antiserum were purified
      using GST-rtER fusion proteins. The specificity of these purified antibodies was
      confirmed by Western blot analysis using extracts from yeast and COS-1 cells
      transfected with rtER cDNA expression vectors. In these cells, rtER level was
      about 300-500 fmol/mg of protein, and the receptor was found as a single band
      migrating as a 65 kDa polypeptide. Interestingly, Western blot analysis with both
      purified antibodies directed against central or C-terminal regions of rtER
      revealed two receptor forms in trout liver nuclear extracts: a major form
      migrating as 65 kDa protein also observed in transfected cells, and a minor band
      at 71 kDa specific to the liver. Both receptor form levels were strongly induced
      by estradiol whereas they were virtually undetectable in untreated male trout
      livers. Immunocytochemistry performed on brain and pituitary of female trout
      revealed the presence of rtER in neurons located in the ventral telencephalon,
      preoptic area and mediobasal hypothalamus, as well as cells in the proximal pars
      distalis of the pituitary.

PMID- 7821710
TI  - Autoradiographic anomaly in 125I-melatonin binding revealed in ovine adrenal.
AB  - Conventional in vitro autoradiographical techniques have been used to screen a
      number of ovine peripheral tissues for the presence of specific 2
      [125I]iodomelatonin binding sites. Intense specific labelling (defined as that
      displaced by 1 microM melatonin) was observed in the adrenal cortex, and less
      intense specific binding in the spleen. Subsequent attempts to characterize these
      adrenal binding sites using in vitro binding assays were unsuccessful. The level
      of specific binding to both crude membranes and to dispersed whole cell
      preparations was negligible, and was not correlated with increasing protein or
      cell concentration. Using quantitative in vitro autoradiography, melatonin was
      found to competitively inhibit 2-[125I]iodomelatonin binding to sections of the
      adrenal cortex, but with a considerably lower affinity (IC50 of 1 microM) than
      that obtained for the ovine pars tuberalis (IC50 of 150 pM) under identical
      conditions. These results suggest that under the conditions of in vitro
      autoradiography, 2-[125I]iodomelatonin binds to a finite number of non-receptor
      sites which are restricted to the ovine adrenal gland. The ability to visualize
      these sites in the present study may arise through the use of an inappropriately
      high excess of unlabelled melatonin (1 microM). Consequently to avoid this
      potential problem, non-specific labelling should perhaps more appropriately be
      defined as binding in the presence of a concentration of melatonin at
      approximately 100-fold the value of the Kd (i.e. 10 nM).

PMID- 7821711
TI  - NIH/3T3 cells transformed with the activated erbB-2 oncogene can be
      phenotypically reverted by a kinase deficient, dominant negative erbB-2 variant.
AB  - A single missense mutation in the human erbB-2 proto-oncogene (HER2N) efficiently
      transforms cultured NIH/3T3 fibroblasts. The transforming allele (HER2VE)
      contains a glutamic acid residue at position 659, instead of a valine, in the
      transmembrane region of the growth factor receptor. Receptor action is dependent
      on oligomerization. We have investigated the ability of erbB-2 gene variants with
      mutations in the intracellular tyrosine kinase domain to revert the transformed
      phenotype of cells. These variants most likely form hetero-oligomers with the
      transforming oncogene. Two receptor variants were constructed and introduced into
      cells expressing the oncogenic form of the human erbB-2 gene, HER2VE. The mutant
      HER2N delta contains a deletion of a large part of the kinase domain including
      the ATP binding site. This mutant had no effect on the growth of transformed
      cells, although it was found to interact with HER2VE. HER2N delta is
      phosphorylated in the presence, but not in the absence of HER2VE. A second mutant
      was constructed, HER2VEK753A, which contains both a mutation in the transmembrane
      region and a mutation in the ATP binding site of the kinase domain. This mutant
      led to a reversion of the transformed phenotype and significantly decreased
      growth in soft agar of HER2VE transformed cells. A concomitant increase in
      phosphorylated receptors was observed. These results indicate that an intact
      kinase domain is required for the oncogenic action of HER2VE and that
      transformation parameters can be suppressed by kinase domain mutants.

PMID- 7821712
TI  - Cytochrome P-450scc activity and substrate supply in human placental
      trophoblasts.
AB  - The degree of saturation of cytochrome P-450scc with cholesterol and the
      substrate turnover number of the cytochrome in cultured trophoblasts and
      mitochondria from the human placenta were investigated. Cholesterol sulfate was
      found to be a suitable substrate for probing the degree of saturation of
      cytochrome P-450scc with substrate during culture and in isolated mitochondria,
      since it enabled the maximum velocity of the cholesterol side-chain cleavage
      reaction to be estimated. In contrast, 25-hydroxycholesterol and low density
      lipoprotein supported trophoblast progesterone production at lower rates than
      that measured with saturating cholesterol sulfate. In the absence of exogenous
      substrate, the highest rate of progesterone synthesis by trophoblasts was
      observed at the beginning of the culture. With cholesterol sulfate as substrate,
      the turnover number of cytochrome P-450scc in cultured cells was 2.8 min-1 and
      was not significantly different to the turnover number of the cytochrome for
      placental mitochondria, where cholesterol is known to be saturating. Results
      indicate that cholesterol is limiting for progesterone synthesis in cultured
      trophoblasts even in the presence of lipoprotein rich medium and 8-bromo-cAMP.
      The concentration of cytochrome P-450scc in trophoblasts was only 20% of that
      measured for placental homogenate suggesting an induction of the cytochrome
      occurs when the trophoblasts fuse in vivo to form syncytiotrophoblasts.

PMID- 7821713
TI  - Evidence against roles for pertussis toxin sensitive G proteins or diacylglycerol
      generation in insulin-like growth factor-1 stimulated DNA synthesis in MG-63
      osteosarcoma cells.
AB  - A pertussis toxin-sensitive G protein has been reported to play a role in the
      mitogenic response to insulin-like growth factor-I (IGF-I) in mouse fibroblasts,
      and diacylglycerol generation has been shown to accompany growth stimulation by
      IGF-I of several cell lines. We have examined the roles of pertussis toxin
      sensitive G proteins and diacylglycerol generation in signaling by the insulin
      like growth factor-I receptor in a cell line that is very responsive to IGF-I,
      the human osteosarcoma cell line, MG-63. Pertussis toxin failed to inhibit IGF-I
      induced [3H]-thymidine incorporation into DNA. Furthermore, the stable analog GTP
      gamma S had no effect on the binding of 125I-labelled IGF-I to MG-63 membrane
      preparations. Following addition of IGF-I to growth-arrested MG-63 cells there
      was no increase in diacylglycerol levels over 30 min. We conclude that the
      activated IGF-I receptor does not use pertussis toxin sensitive G proteins or
      diacylglycerol generation in a pathway leading to DNA synthesis in MG-63 cells.

PMID- 7821714
TI  - The androgen receptor of the urogenital tract of the fetal rat is regulated by
      androgen.
AB  - To provide insight into androgen-mediated virilization, we measured the androgen
      receptor in tissues of male and female rat fetuses prior to and during the period
      of phenotypic sex differentiation. Western immunoblotting was performed utilizing
      an antibody directed against the 21 amino-terminal segment of the androgen
      receptor. In immunoblots prepared from urogenital tract tissues of day 17 male
      and female fetal rats, this antibody specifically recognizes a 110K protein band
      characteristic of the androgen receptor. Androgen receptor levels were low to
      undetectable in a variety of non-urogenital tract tissues. After day 18 of fetal
      development, the amount of androgen receptor decreased in female urogenital
      tissues, and by day 22 the amount of immunoreactive androgen receptor was higher
      in the male urogenital sinus and tubercle than in the corresponding tissues of
      the female. Administration of 5 alpha-dihydrotestosterone to pregnant rats at a
      dose of 50 mg/kg body weight per day from day 12 to day 22 caused an increase in
      immunoreactive androgen receptor in the female urogenital sinus and tubercle to
      levels approaching those in male tissues. Administration of the androgen
      antagonist flutamide (100 mg/kg body weight per day) during the same interval
      caused a reduction in androgen receptor level in the urogenital sinus and
      tubercle of the male. These findings suggest that androgens modulate the amount
      of androgen receptor in the embryonic urogenital tract either by inducing the
      proliferation of androgen-responsive cells or by increasing androgen receptor
      levels in individual cells.

PMID- 7821715
TI  - Quantitative increases in DNA binding affinity and positional effects determine 9
      cis retinoic acid induced activation of the retinoid X receptor beta homodimer.
AB  - Retinoid X receptors (RXRs) exert transcriptional activities through
      heterodimerization with members of the nuclear hormone receptor superfamily. RXRs
      also act as homodimers and stimulate transcription from an RXR responsive element
      (RXRE) when bound to 9-cis-retinoic acid (9cRA). Here direct effects of 9cRA have
      been examined on biochemical and mechanistic parameters of RXR beta. It is shown
      that 9cRA significantly increases RXR beta homodimer binding affinity to an RXRE
      (Kd without ligand = 18 nM, Kd with ligand = 6 nM), while decreasing
      significantly the affinity of RXR beta/thyroid hormone receptor (T3R alpha)
      heterodimer binding to the same element. Effects on other response elements are
      also examined. The RXR beta homodimer was found to contact both halves of the
      RXRE direct repeat, irrespective of the effect of added ligand, while the RXR
      beta/T3R alpha heterodimer contacted the element only through a specific half
      site. Binding of the homodimer to the element functionally activates RXR beta,
      since RXR beta enhanced transcription in vitro from a specific template in a
      ligand-dependent fashion. In agreement, transfection of RXR beta alone (but not
      RXR beta/T3R alpha) led to ligand-dependent activation of a reporter containing
      the RXRE. Taken together, 9cRA facilitates functional activation of the RXR beta
      homodimer in an element-dependent manner.

PMID- 7821716
TI  - hCG-induced changes in LH/CG receptor mRNA transcript levels in the testis of
      adult hypophysectomized, ethane dimethyl sulphonate-treated rats.
AB  - To elucidate the molecular mechanisms involved in the development of precursor
      cells into functional Leydig cells, effects of hCG on the expression of the
      luteinizing hormone (LH)/chorionic gonadotrophin (CG) receptor gene were
      investigated in the testis of adult hypophysectomized, ethane dimethyl sulphonate
      (EDS)-treated rats. The alkylating drug EDS specifically destroys Leydig cells in
      the adult rat testis. In hypophysectomized rats, in the absence of LH, this is
      not followed by the formation of new Leydig cells, leaving a testis in which
      Leydig cell precursors are presumed to be the only cell type that possess LH
      receptors. The absence of Leydig cells was confirmed by determining the gene
      expression of two key steroidogenic enzymes, 3 beta-hydroxysteroid
      dehydrogenase/isomerase (3 beta HSD) and P-450 17 alpha-hydroxylase/C17-20 lyase
      (P-45017 alpha) in these animals. Northern blot analysis revealed that
      hypophysectomy, followed by EDS treatment decreased the total amount of LH/CG
      receptor mRNA and drastically changed the pattern of LH/CG receptor mRNA
      transcripts. In the testis of intact adult rats, the expression of the LH/CG
      receptor gene results in multiple mRNA transcripts with molecular sizes of
      approximately 7.0, 4.2, 2.5, 1.8 and 1.2 kb. The most abundant species observed
      in the testis of adult hypophysectomized, EDS-treated rats was the 1.8 kb mRNA
      transcript, whereas the levels of the other mRNA transcripts were decreased. To
      stimulate the development of precursor cells into functional Leydig cells,
      hypophysectomized, EDS-treated rats were treated with high doses of hCG (100 IU)
      for different periods of time.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7821717
TI  - Thyroid hormone and glucocorticoid independently regulate the expression of
      estrogen receptor in male Xenopus liver cells.
AB  - Earlier studies from our laboratory had shown that triiodothyronine (T3) strongly
      potentiates the activation by estradiol (E2) of silent vitellogenin (Vit) genes
      and the autoinduction of estrogen receptor (ER) mRNA in primary cultures of male
      Xenopus hepatocytes (Rabelo and Tata, 1993). It was, however, not known if T3, or
      other hormones, could up-regulate ER mRNA in the absence of exogenous E2. We now
      show that T3 and dexamethasone (Dex), but not progesterone and testosterone,
      directly induce ER mRNA within 4 h by separate pathways, at doses compatible with
      the Kd values of their receptors. This induction of ER mRNA is accompanied by a
      marked enhancement of the activation of the silent Vit B1 gene if E2 is added by
      12 h after T3 and Dex, thus suggesting an elevated level of functional ER induced
      by the two hormones. This conclusion was supported by a higher rate of
      transcription from an estrogen response element (ERE)-tk-CAT construct
      transfected into cultured hepatocytes pre-treated with T3 and Dex before
      incubation with estrogen. Our findings emphasize the importance of hormonal
      interplay via auto- and cross-regulation of nuclear hormone receptors.

PMID- 7821718
TI  - Localization of urokinase- and tissue-type plasminogen activator mRNAs in rat
      testes.
AB  - The expressions of urokinase (uPA) and tissue-type plasminogen activators (tPA)
      in different stages of the rat seminiferous epithelial cycle were analyzed by in
      situ and Northern hybridizations combined with zymographic analysis. Irradiated
      rat testes were used to assess the cell localization. Both of the plasminogen
      activators were expressed in a strictly stage specific manner. Maximal expression
      of uPA mRNA was seen in Sertoli cells during stages VII-VIII of the cycle. The
      same expression in the basal compartment of the tubules was detected at 7 days
      post-irradiation (p-i), during a selective reduction of spermatogonia and
      preleptotene spermatocytes. Levels of tPA mRNA started to accumulate in Sertoli
      cells at stage VIII and were high during stages IX-XII and detectable during
      stages XIII-XIV. At 26 days p-i, reduction of pachytene spermatocytes, which are
      shown to be immunoreactive for tPA, did not have an effect on tPA mRNA
      expression. Catalytic activities of uPA and tPA changed concomitantly to their
      RNA levels in different stages of the cycle. However, at 7 days p-i, uPA activity
      was decreased at stages VII-VIII of the cycle suggesting that germ cell Sertoli
      cell interaction is important for uPA activity.

PMID- 7821719
TI  - Ontogeny of glucocorticoid and D2 receptors in the rat pituitary: an in situ
      hybridization study.
AB  - The expression of glucocorticoid and D2 dopamine receptors (GR and D2R) during
      rat pituitary ontogenesis was studied by in situ hybridization (ISH). On early
      stages, E13-E14, a weak specific signal for GR mRNA was obvious in the whole
      Rathke's pouch (RP) whereas subsequently, from E17-E18, strong labelling was
      restricted to the anterior lobe (AL) and the neural lobe (NL). At the same time,
      D2R mRNAs appeared in the intermediate lobe (IL) and the long isoform of the D2R
      (D2R 444) was detectable with specific probes. On the postnatal stages, until
      adult, GR mRNA, if present, was always undetectable in the IL using the
      conventional ISH technique. These data indicate a possible early regulation of
      POMC gene expression by glucocorticoid in corticotrophic cells of the AL and by
      dopamine in the melanotrophic cells of the IL. The possibility of a negative
      regulation of GR mRNA by dopamine (DA) in the IL as soon as E17 is discussed.

PMID- 7821720
TI  - Immunocytochemical localization of prolactin receptors in rat liver cells: I.
      Dependence on sex and sex steroids.
AB  - The peculiarities of cellular and tissue distribution of prolactin receptors
      (PRLR) in the liver of female and male rats with different sex steroid status
      were investigated in paraplast-embedded tissue with the indirect immunoperoxidase
      technique. Two clones of antibodies directed outside the PRL-binding site (U6) or
      to the PRL-binding site (T6) of the receptor were used. PRLR-specific
      immunoreactivity was identified essentially in hepatocytes. PRLR can be
      visualized in sinusoidal domains of cellular membranes, in cytoplasmic granules
      and sometimes in the perinuclear area of hepatocytes. The staining
      characteristics were similar with both antibodies. There were no prominent
      differences in the intensity of PRLR-positive staining among hepatocytes of
      different zones of hepatic lobules with the exception of some hepatocytes around
      central veins. Sex differences in the intensity of immunostaining (strong in
      females, and faint in males) but not in the amount and distribution of PRLR
      containing cells were observed. Gonadectomy of animals caused the disappearance
      of sex differences in the intensity of PRLR-positive staining as a result of its
      decrease in females and increase in males. The essential elevation in the
      intensity of PRLR-specific immunoreactivity was revealed in hepatocytes of
      gonadectomized females and males after prolonged estradiol administration (10
      micrograms for 14 days). The cytoplasmic staining of some hepatocytes surrounding
      central veins was much more pronounced in estrogenized animals. PRLR-specific
      immunoreactivity in the perinuclear area was identified in these cells. Androgen
      treatment (3 mg of testosterone-propionate for 3 days) of gonadectomized animals
      caused a decrease in the intensity of hepatocyte PRLR-positive staining similarly
      in both sexes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7821721
TI  - G-proteins and adenylyl cyclase in ovarian granulosa cells of amago salmon
      (Oncorhynchus rhodurus).
AB  - The involvement of guanine nucleotide-binding regulatory proteins (G-proteins)
      and adenylyl cyclase in the gonadotropin stimulation of cAMP was investigated
      using crude membrane fractions from granulosa cells of amago salmon (Oncorhynchus
      rhodurus) postvitellogenic ovarian follicles. Although cholera toxin-catalyzed
      ADP ribosylation occurred in 45- and 50-kDa proteins, only the former was
      recognized by an antibody against the alpha-subunit of Gs. With pertussis toxin,
      only the 41-kDa protein was ADP-ribosylated. This 41-kDa protein was recognized
      by an antibody against the alpha-subunit of Gi. Partially purified chum salmon
      gonadotropin (SGA) stimulated adenylyl cyclase activity in crude membrane
      preparations of granulosa cells only in the presence of pertussis toxin in the
      incubation medium. Adenosine inhibited adenylyl cyclase in the presence of GTP
      and pertussis toxin reversed it. Unlike SGA, forskolin, which acts upon adenylyl
      cyclase without G-protein interaction, markedly stimulated adenylyl cyclase
      activity in the absence of pertussis toxin. These results provide evidence that
      both stimulatory (Gs) and inhibitory (Gi) regulation by adenylyl cyclase operates
      in the granulosa cells of amago salmon postvitellogenic ovarian follicles. It is
      possible that, although a stimulatory receptor interacts with Gs, its activity is
      influenced by the functional state of Gi.

PMID- 7821722
TI  - Signal transduction in the inhibition of juvenile hormone biosynthesis by
      allatostatins: roles of diacylglycerol and calcium.
AB  - The effects of pharmacological agents that interfere with the 1,4,5-inositol
      trisphosphate (IP3)/diacylglycerol (DAG) pathway on juvenile hormone (JH)
      biosynthesis by corpora allata (CA) of the cockroach Diploptera punctata have
      been investigated. These effects were assessed in the presence of the inhibitory
      neuropeptides, allatostatins, with a view to elucidating the pathway for signal
      transduction in the inhibition of JH biosynthesis. Treatment of CA with
      inhibitors of DAG kinase to elevate the concentration of DAG within the CA cells,
      resulted in a significant, dose-dependent decrease in JH biosynthesis.
      Simultaneous treatment of glands with both DAG kinase inhibitors and
      allatostatins further enhanced this effect, suggesting that DAG is an
      intermediate in the allatostatin-induced inhibition of JH production. The
      inhibitory actions of the phorbol ester activator of PKC, PDBu, or of
      allatostatin on JH biosynthesis were partially blocked by pre-incubating the CA
      with PKC inhibitors. Treatment of CA with the calcium-mobilizing drug
      thapsigargin resulted in a significant stimulation in JH biosynthesis in glands
      from mated females producing JH at high rates. Thapsigargin was also able to
      reverse the effect of allatostatins in high-activity mated CA. This suggests an
      involvement of the other product of phosphoinositide hydrolysis, IP3, in the
      modulation of JH biosynthesis at specific developmental times and in glands
      showing specific levels of activity.

PMID- 7821723
TI  - Proceedings of the Minkowski Prize Winner symposium. Held on the occasion of the
      29th annual meeting of the EASD, Istanbul, 4-5 September 1993.

PMID- 7821724
TI  - Implantable insulin pumps and metabolic control.
AB  - The development of implantable, remote-controlled insulin pumps dates back to the
      early 1970's when it was recognized that conventional insulin therapy may be
      inadequate to control microvascular complications. For the first prototypes the
      intraperitoneal access route was favoured because of a physiological
      portal/peripheral insulin gradient. With intraperitoneal insulin delivery
      excellent metabolic control can be obtained with glycohaemoglobin values close to
      the upper normal range. Although long-term studies in insulin-dependent diabetic
      patients show comparable results with respect to glycaemic control and
      intermediary substrate levels with intensive conventional therapy, the advantage
      of intraperitoneal insulin delivery may lie in the low rate of hypoglycaemic
      episodes.

PMID- 7821725
TI  - Glucose induces oscillatory Ca2+ signalling and insulin release in human
      pancreatic beta cells.
AB  - Mechanisms of pulsatile insulin release in man were explored by studying the
      induction of oscillatory Ca2+ signals in individual beta cells and islets
      isolated from the human pancreas. Evidence was provided for a glucose-induced
      closure of ATP-regulated K+ channels, resulting in voltage-dependent entry of
      Ca2+. The observation of step-wise increases of capacitance in response to
      depolarizing pulses suggests that an enhanced influx of Ca2+ is an effective
      means of stimulating the secretory activity of the isolated human beta cell.
      Activation of muscarinic receptors (1-10 mumol/l carbachol) and of purinergic P2
      receptors (0.01-1 mumol/l ATP) resulted in repetitive transients followed by
      sustained elevation of the cytoplasmic Ca2+ concentration ([Ca2+]i). Periodic
      mobilisation of intracellular calcium was seen also when injecting 100 mumol/l
      GTP-gamma-S into beta cells hyperpolarized to -70 mV. Individual beta cells
      responded to glucose and tolbutamide with increases of [Ca2+]i, manifested either
      as large amplitude oscillations (frequency 0.1-0.5/min) or as a sustained
      elevation. Glucose regulation was based on sudden transitions between the basal
      and the two alternative states of raised [Ca2+]i at threshold concentrations of
      the sugar characteristic for the individual beta cells. The oscillatory
      characteristics of coupled cells were determined collectively rather than by
      particular pacemaker cells. In intact pancreatic islets the glucose induction of
      well-synchronized [Ca2+]i oscillations had its counterpart in 2-5 min pulses of
      insulin. Each of these pulses could be resolved into regularly occurring short
      insulin transients. It is concluded that glucose stimulation of insulin release
      in man is determined by the number of beta cells entering into a state with
      Ca(2+)-induced secretory pulses.

PMID- 7821726
TI  - Functional aspects of mouse islets transplanted to the kidney.
AB  - To test whether the transplantation of pancreatic islets affects their basic
      functions, collagenase-isolated mouse islets were inserted under the left renal
      capsule of recipient animals. After various periods of time, grafts were removed
      from the kidney and examined for insulin content and secretory dynamics in a
      perifusion system. During syngeneic (C57BL/6, BALB/c) or subsyngeneic (NMRI)
      intrastrain transplantation, the graft insulin content fell drastically during
      the first week and stayed low for at least 6 weeks; first-phase secretion in
      general appeared suppressed. Immunosuppression by cyclosporin A had little effect
      on (sub)syngeneic grafts but markedly improved the performance of
      allotransplants. Daily injections of the calcium antagonist, verapamil, enhanced
      the insulin secretory responses of isolated grafts, whether (sub)syngeneic or
      allogeneic. In syngeneic and subsyngeneic grafts, the potentiating effect of
      acetylcholine on glucose-induced insulin release was markedly diminished, whereas
      that of caffeine was not. Transplanted islets also exhibited a subnormal
      responsiveness to the inhibiting action of noradrenaline. It is concluded that
      chronic denervation and transplantation of pancreatic islets may cause
      fundamental changes in the beta-cell responses to physiological regulators of
      insulin release.

PMID- 7821727
TI  - Insulin receptor internalization: molecular mechanisms and physiopathological
      implications.
AB  - The initial interaction between insulin and its receptor on target cell surface
      is followed by a series of surface and intracellular steps which participate in
      the control of insulin action. Abnormalities of any of these steps could result
      in mishandling of the receptor leading to defective modulation of receptor number
      on the cell surface and to inappropriate cell sensitivity to the hormone. Thus,
      the identification of each of these steps as well as understanding the mechanisms
      governing them is obligatory to unravel some aspects of the pathogenesis of
      insulin resistance states. This was the goal of the studies we have carried out
      during recent years using combined molecular and cellular biology as well as
      biochemical techniques. These studies allowed us to propose the following ordered
      sequence of events: 1) insulin binds to receptors preferentially associated with
      microvilli on the cell surface; 2) insulin triggers receptor kinase activation
      and autophosphorylation which not only results in initiation of the various
      biological signals leading to insulin action but also in redistribution of the
      hormone-receptor complex in the plane of the membrane; 3) on the non-villous
      domain of the cell surface, insulin receptors anchor to clathrin-coated pits
      through specific "internalization sequences" present in their cytoplasmic
      juxtamembrane domain; 4) insulin-receptor complexes are internalized together
      with other receptors present in the same clathrin-coated pits through the
      formation of clathrin-coated vesicles; 5) the complexes are delivered to
      endosomes, the acidic pH of which induces the dissociation of insulin molecules
      from insulin receptors and their sorting in different directions; 6) insulin
      molecules are targetted to late endosomes and lysosomes where they are degraded;
      7) receptors are recycled back to the cell surface in order to be reused.

PMID- 7821728
TI  - Signalling through the insulin receptor and the insulin-like growth factor-I
      receptor.
AB  - The insulin receptor and the insulin-like growth factor I receptor belong to the
      family of tyrosine kinase receptors. Both receptors appear as a disulphide-linked
      dimer; each half of the dimer consisting of a 130 k M(r) alpha-subunit linked to
      a 90 k M(r) beta-subunit. Both halves of the dimer are linked together by
      disulphide bonds to form an alpha 2 beta 2 structure. The insulin receptor
      functions as an allosteric enzyme in which the binding of the hormone to the
      alpha-subunit leads to a series of conformational changes resulting in activation
      of the beta-subunit tyrosine kinase. Upon multisite autophosphorylation the
      latter becomes competent to phosphorylate cellular substrates resulting in the
      biological responses of insulin. Recent findings have recognized the mitogen
      activated protein kinase cascade as a central signalling circuitry linking cell
      surface receptors, such as the insulin receptor, to the nucleus, and playing a
      role in regulation of metabolism, growth and differentiation.

PMID- 7821729
TI  - The structural basis of insulin and insulin-like growth factor-I receptor binding
      and negative co-operativity, and its relevance to mitogenic versus metabolic
      signalling.
AB  - Insulin and insulin-like growth factor-I exhibit a set of non-classical receptor
      binding properties suggestive of negative co-operativity or site-site
      interactions between the two receptor halves: curvilinear Scatchard plots,
      acceleration of dissociation of bound labelled ligand at high dilution in the
      presence of unlabelled ligand. The alpha 2 beta 2 receptor dimer binds only one
      ligand molecule with high affinity. The dose-response curve for the acceleration
      of 125I-insulin by unlabelled insulin is bell-shaped, with a disappearance of the
      negative co-operativity at insulin concentrations over 0.1 mumol/l. This
      phenomenon had been attributed to insulin dimerization, but new data with non
      dimerizing analogues and insulins modified at the hexamer-forming surface
      indicate the presence of a second binding site on the insulin molecule's hexamer
      face. This site binds to a second domain on the receptor. A new binding model for
      insulin and insulin-like growth factor-I is proposed where the bivalent ligand
      bridges the two receptor alpha subunits alternatively at opposite sites in a
      symmetrical receptor structure. The implications of the model for negative co
      operativity, bell-shaped biological curves, and the divergence between mitogenic
      and metabolic signalling are discussed in the context of the evolution of the
      properties of insulin and insulin-like growth factor-I.

PMID- 7821730
TI  - Modulation of insulin receptor signalling: significance of altered receptor
      isoform patterns and mechanism of hyperglycaemia-induced receptor modulation.
AB  - Insulin resistance of the skeletal muscle plays a key role in the development of
      the metabolic endocrine syndrome and its further progression to non-insulin
      dependent diabetes (NIDDM). Available data suggest that insulin resistance is
      caused by an impaired signal from the insulin receptor to the glucose transport
      system and to glycogen synthase. The impaired response of the insulin receptor
      tyrosine kinase which is found in NIDDM appears to contribute to the pathogenesis
      of the signalling defect. The reduced kinase activation is not caused by
      mutations within the insulin receptor gene. We investigated two potential
      mechanisms that might be relevant for the abnormal function of the insulin
      receptor in NIDDM, i.e. changes in the expression of the receptor isoforms and
      the effect of hyperglycaemia on insulin receptor tyrosine kinase activity. The
      insulin receptor is expressed in two different isoforms (HIR-A and HIR-B). We
      found that HIR-B expression in the skeletal muscle is increased in NIDDM.
      However, the characterisation of the functional properties of HIR-A and HIR-B
      revealed no difference in their tyrosine kinase activity in vivo. The increased
      expression of HIR-B might represent a compensatory event. In contrast,
      hyperglycaemia might directly inhibit insulin-receptor function. We have found
      that in rat-1 fibroblasts which overexpressing human insulin receptor an
      inhibition of the tyrosine kinase activity of the receptor may be induced by high
      glucose levels. This appears to be mediated through activation of certain protein
      kinase C isoforms which form stable complexes with the insulin receptor and
      modulate the tyrosine kinase activity of the insulin receptor through serine
      phosphorylation of the receptor beta subunit.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7821731
TI  - Mechanisms modifying glucose oxidation in diabetes mellitus.
AB  - The Glucose Fatty Acid Cycle as formulated 30 years ago and reviewed in the
      Minkowski lecture in 1966 described short term effects of fatty acids (minutes)
      to decrease uptake, glycolysis and oxidation of glucose in heart and skeletal
      muscles. Such short term effects have since been extended to include inhibition
      of glucose uptake and glycolysis and stimulation of gluconeogenesis in liver and
      these effects have also been convincingly demonstrated in man in vivo. More
      recently a longer term effect of fatty acid metabolism to decrease glucose
      oxidation (hours) has been shown in heart and skeletal muscle and liver. This
      effect increases the specific activity of pyruvate dehydrogenase kinase, which in
      turn results in enhanced phosphorylation and inactivation of the pyruvate
      dehydrogenase complex. Activity of the pyruvate dehydrogenase complex is the
      major determinant of glucose oxidation rate. It seems likely that longer term
      effects of fatty acids on this and other aspects of glucose metabolism could be
      important in the development of insulin resistance in diabetes mellitus in man.

PMID- 7821732
TI  - The pathogenesis of NIDDM.
AB  - Improvements in the specificity and sensitivity of assays for insulin-related
      molecules in the circulation have proved to be necessary and informative in
      studies of the pathogenesis of non-insulin-dependent diabetes (NIDDM). Of
      particular interest has been the close relationship between increases in des
      31,32 split proinsulin and susceptibility to loss of glucose tolerance and the
      insulin resistance syndrome. It is suggested that the analogy can be drawn
      between this measurement and the measurement of HbA1c. The amount of this
      partially processed precursor of insulin in the circulation indicates the degree
      of glucose stimulus applied to the beta cell combined with the inherent capacity
      of the insulin secretory system to respond. Further improvements of the
      sensitivity and specificity of the assay of proinsulin related molecules are
      desirable. Deterioration of the early insulin response to oral glucose is a major
      feature of the loss of glucose tolerance associated with the transition from
      normal to impaired glucose tolerance and to NIDDM. The extent to which this loss
      of insulin secretion reflects a major predisposing factor in the aetiology of
      this type of diabetes or is secondary to glucose toxicity or amyloid accumulation
      remains to be determined. A relationship between birth weight and impaired
      glucose tolerance, NIDDM and the insulin resistance syndrome has now been
      observed in two populations in the UK, in Mexican Americans and in Pima Indians.
      It is therefore reproducible and applicable to widely differing populations. Much
      further research is indicated to determine, amongst many questions, how much
      diabetes is associated with this link and what factors explain it.

PMID- 7821733
TI  - Central nervous system and peripheral abnormalities: clues to the understanding
      of obesity and NIDDM.
AB  - To study the impact on glucose handling of the observed hyperinsulinaemia and
      hypercorticism of the genetically obese fa/fa rats, simplified animal models were
      used. In the first model, normal rats were exposed to hyperinsulinaemia for 4
      days and compared to saline-infused controls. At the end of this experimental
      period, the acute effect of insulin was assessed during euglycaemic
      hyperinsulinaemic clamps. White adipose tissue lipogenic activity was much more
      insulin responsive in the "insulinized" than in the control groups. Conversely
      muscles from "insulinized" rats became insulin resistant. Such divergent
      consequences of prior "insulinization" on white adipose tissue and muscle were
      corroborated by similar divergent changes in glucose transporter (GLUT 4) mRNA
      and protein levels in these respective tissues. In the second model, normal rats
      were exposed to stress levels of corticosterone for 2 days. This resulted in an
      insulin resistance of all muscle types that was due to an increased glucose-fatty
      acid cycle, without measurable alteration of the GLUT 4 system. In genetically
      obese (fa/fa) rats, local cerebral glucose utilization was decreased compared to
      lean controls. This could be the reason for adaptive changes leading to increased
      levels in their hypothalamic neuropeptide Y levels and median eminence
      corticotropin-releasing-factor. Thus, in a third model, neuropeptide Y was
      administered intracerebroventricularly to normal rats for 7 days. This produced
      hyperinsulinaemia, hypercorticosteronaemia, as well as most of the metabolic
      changes observed in the genetically obese fa/fa rats, including muscle insulin
      resistance. These data together suggest that the aetiology of obesity-insulin
      resistance of genetically obese rodents has to be searched within the brain, not
      peripherally.

PMID- 7821734
TI  - Recombinant human insulin-like growth factor-I: a therapeutic challenge for
      diabetes mellitus.
AB  - Insulin-like growth factor I (IGF I) is an endocrine hormone that mediates most
      of the effects of pituitary growth hormone. Other important regulatory factors of
      serum IGF I levels are insulin and nutrition. Most of the circulating IGF I is
      bound to three IGF binding proteins (BP), mostly IGFBP-3, BP-2 and BP-1. IGF I is
      also produced by many cells in the body where it exerts autocrine and/or
      paracrine effects. IGF I has a specific receptor on most cells, the so-called
      type 1 IGF receptor. When IGF I is administered intravenously as a bolus it leads
      to acute hypoglycaemia in a similar way to insulin and mainly with the insulin
      receptor. Chronic administration of IGF I to hypophysectomized or diabetic rats
      leads to prominent anabolic effects and growth. In this manuscript, metabolic and
      endocrine effects of recombinant IGF I are discussed. Recombinant IGF I therapy
      increases energy expenditure and lipid oxidation and decreases proteolysis and
      protein oxidation. These effects occur despite a partial inhibition of insulin
      and growth hormone secretion. The therapeutic spectrum of recombinant IGF I,
      consisting of inhibition of catabolism, stimulation of anabolism, decreases of
      triglyceride and cholesterol levels and a striking increase in insulin
      sensitivity, renders IGF I a very interesting, powerful tool for insulin
      resistant states such as non-insulin-dependent diabetes mellitus.

PMID- 7821736
TI  - Transcription of the insulin gene: towards defining the glucose-sensitive cis
      element and trans-acting factors.
AB  - Previous work has shown that the sequence -196 to -247 of the rat insulin I gene
      mediates the stimulatory effect of glucose in fetal islets. We have used adult
      rat and human islets to delineate the glucose-sensitive cis-element to the
      sequence -193 to -227. In electrophoretic mobility shift assays, a 22 bp
      nucleotide corresponding to the sequence -206 to -227 bound all the nuclear
      proteins that could be bound by the entire minienhancer sequence -196 to -247.
      The rat insulin I sequence -206 to -227 formed three major complexes; in
      contrast, the corresponding human insulin sequence formed one single band with
      human and rat islet nuclear extracts, corresponding to the complex C1 of the rat
      insulin gene. Incubation of islets with varying glucose levels resulted in a dose
      dependent increase in the intensity of the C1 band, while the other nuclear
      complexes formed with the insulin sequence, or the AP1 and SP1 binding activities
      used as control, were glucose insensitive. This is thus the first demonstration
      of a physiologic glucose-sensitive trans-acting factor for the insulin gene,
      whose further study may markedly enhance our understanding of the regulation of
      insulin biosynthesis in normal and diabetic beta cells. Furthermore, once cloned,
      the introduction of this glucose sensitive factor may enable the construction of
      truly physiologic artificial beta cells.

PMID- 7821735
TI  - Protein phosphorylation and beta-cell function.
AB  - The central role of reversible protein phosphorylation in regulation of beta-cell
      function is reviewed and the properties of the protein kinases so far defined in
      beta cells are summarised. The key effect of Ca2+ to initiate insulin secretion
      involves activation of a Ca2+/calmodulin-dependent protein kinase. Potentiation
      of secretion by agents activating protein kinase A or C appears to involve an
      increase in the sensitivity of the secretory system to intracellular Ca2+. The
      effects of MgATP on the binding of [3H]-glibenclamide to the beta-cell
      sulphonylurea receptor suggest that the properties of this receptor, which
      controls the activity of ATP-sensitive K-channels, are modulated by
      phosphorylation. The identity of the kinases and phosphatases responsible is not
      known but the presence in beta-cell membranes of various kinases not dependent on
      Ca2+ or cyclic AMP, and including tyrosine kinase, is documented, together with
      the presence of both Ca(2+)-dependent and Ca(2+)-independent protein
      phosphatases. Protein phosphorylation is also involved in regulation of beta-cell
      Ca2+ fluxes and evidence is presented that protein kinase C activation inhibits
      Ca2+ signalling by reducing influx of Ca2+ into the beta cell. The identity of
      the Ca2+/calmodulin-dependent protein kinase activity in beta cells is discussed.
      Comparison of its properties towards substrates and inhibitors with those of
      brain Ca2+/calmodulin-dependent protein kinase II suggests that the beta-cell
      enzyme may be similar or identical to the brain enzyme.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7821737
TI  - Regulation of insulin secretion: the role of second messengers.
AB  - This review summarises briefly studies performed in the last 5-6 years concerning
      the role of second messengers in the regulation of insulin secretion, using
      intact and electrically permeabilized rat islets of Langerhans. It is concluded
      that cyclic AMP (through protein kinase A), calcium (through calcium-calmodulin
      dependent protein kinases) and diacylglycerol (through protein kinase C) may be
      important second messengers in modulating the effects of specific secretagogues
      on insulin release. However, recent studies strongly suggest that neither protein
      kinase A nor protein kinase C are directly involved in the regulation of insulin
      secretion by glucose. The possible involvement of other second messengers, nitric
      oxide and arachidonic acid, in the regulation of secretion is also briefly
      reviewed.

PMID- 7821738
TI  - The beta cell in NIDDM: giving light to the blind.
AB  - Impairment of glucose-induced insulin secretion in non-insulin-dependent diabetes
      mellitus (NIDDM) may be caused by GLUT 2 underexpression in the pancreatic beta
      cell, a mutation of the glucokinase gene, glucose 6-phosphatase overactivity, FAD
      linked glycerophosphate dehydrogenase deficiency, a mitochondrial DNA defect
      and/or a secondary phenomenon of so-called glucotoxicity possibly involving
      glycogen accumulation in the beta-cell. It is proposed tht the methyl esters of
      succinic acid and related molecules may represent new tools with which to bypass
      these defects in glucose transport, phosphorylation and further catabolism and,
      hence, to stimulate both proinsulin biosynthesis and insulin release in NIDDM.

PMID- 7821739
TI  - Short-term regulation of glucokinase.
AB  - The activity of liver glucokinase is controlled in the short term by the
      concentration of its substrate glucose and by a regulatory protein, which acts as
      a competitive inhibitor with respect to glucose. In mammalian species, the effect
      of this protein is modulated by fructose 6-phosphate, which reinforces the
      inhibition, and by fructose 1-phosphate which antagonizes it. In the rat, the
      regulatory protein is found in the two tissues that express glucokinase, i.e.,
      the liver and the pancreatic islets. Of particular interest is the fact that the
      regulatory protein is absent from the liver in those species that have no hepatic
      glucokinase. These results indicate that the two proteins form a functional unit.
      The regulatory protein appears in rat liver before birth, whereas glucokinase is
      only synthesized after 15 days of extrauterine life. The concentration of
      regulatory protein in the liver of the adult rat decreases by about 50% during
      starvation and in diabetes mellitus. Under these conditions, the difference
      between the concentrations of regulatory protein and glucokinase remains constant
      at about 0.4-0.5 nmol/g.

PMID- 7821740
TI  - Insulin secretory granule biogenesis and the proinsulin-processing
      endopeptidases.
AB  - The insulin storage granule of the pancreatic beta cell is assembled within the
      trans Golgi network from around 50 or so gene products many of which are
      synthesized coordinately with the major component, proinsulin. An important
      contribution to our understanding of the regulation of this process has come from
      studies of the post-translational processing of proinsulin and of other proteins
      which are stored in the granule, particularly the processing enzymes themselves.
      The present review focusses on recent insights into the molecular nature of the
      processing machinery, and the granule Ca(2+)-dependent subtilisin-related
      endopeptidases which catalyse the initial rate-limiting step in the enzymic
      conversion of proinsulin.

PMID- 7821741
TI  - Physiologic relevance of heterogeneity in the pancreatic beta-cell population.
AB  - In vitro studies on purified rat beta cells have indicated a functional diversity
      among insulin-containing cells. Intercellular differences were found in the rates
      of glucose-induced insulin synthesis and release. They are attributed to
      differences in cellular thresholds for glucose utilization and oxidation, as can
      be caused by varying activities in rate limiting steps such as glucokinase
      dependent phosphorylation. The percent of functionally active beta cells
      increases dose-dependently with the glucose concentration, making cellular
      heterogeneity and its regulation by glucose major determinants for the dose
      response curves of the total beta-cell population. Beta cells which are already
      responsive to low glucose concentrations are characterized by a higher content in
      pale immature granules; their activated biosynthetic and secretory activity
      accounts for preferential release of newly-formed hormone by the total beta-cell
      population. At any glucose level, the amplitude of insulin release depends on the
      percent glucose-activated cells and their cyclic AMP content, an integrator of
      (neuro)hormonal influences. The in vitro described heterogeneity in beta-cell
      functions may bear physiological relevance as several of its characteristics are
      also detectable in intact pancreatic tissue; furthermore, in vitro signs of
      heterogeneity can be altered by prior in vivo treatment indicating that they
      express properties of the cells in their in situ configuration. Elevated basal
      levels of (pro)insulin may reflect the existence of an increased number of beta
      cells that are activated at low physiologic glucose concentrations.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7821742
TI  - Proinsulin processing in the regulated and the constitutive secretory pathway.
AB  - Proinsulin is converted to insulin in beta-cell granules. Conversion involves
      endoproteolytic cleavage at the two pairs of basic residues linking the insulin A
      and B-chains to C-peptide. The sequence of events leading to complete conversion
      differs from one proinsulin species to the next. In man, the structure of the
      proinsulin molecule is such as to favour cleavage at the B-chain/C-peptide
      junction leading to the generation of des-31,32 split proinsulin as the
      predominant, naturally occurring conversion intermediate. Under normal
      circumstances, proinsulin conversion is largely completed before secretion, and
      neither the intact prohormone nor conversion intermediates are thus encountered
      in large quantities in the circulation. In some pathological situations,
      including non-insulin-dependent diabetes, insulinoma and familial
      hyperproinsulinaemia, unusually high ratios of des-31,32 split proinsulin and/or
      proinsulin to insulin have been reported. As we understand the biochemistry of
      proinsulin conversion in increasingly fine molecular detail, it should become
      possible to make use of such unusual ratios to provide insight into lesions
      underlying altered beta-cell function in disease states.

PMID- 7821743
TI  - Molecular biology of IDDM.
AB  - The clinical onset of insulin-dependent diabetes is associated with several
      autoimmune phenomena including islet cell antibodies, glutamic acid decarboxylase
      (the GAD65 isoform) autoantibodies (GAD65Ab) as well as insulin autoantibodies.
      The molecular cloning of these autoantigens has permitted the development of
      precise and reproducible antibody immunoassays to identify marker-positive
      patients and control subjects. Among patients with new-onset diabetes about 70%
      were GAD65Ab positive compared to 1.5% among control subjects while 46% of
      patients had IAA compared to 1% among control subjects. The autoreactive sites or
      epitopes of GAD65 and insulin remain to be determined. The disease association
      with HLA on chromosome 6 may help to define the epitope specificity of the
      autoimmune reaction. Recent data suggest that 95% of new-onset IDDM children (0
      15 years of age) are positive for either DQ2, DQ8 or both compared to about 50%
      of healthy control subjects. HLA-DQ6 is negatively associated with the disease.
      Both HLA-DQ2 and DQ8 therefore seem to be necessary, but not sufficient for
      diabetes. Molecular modelling suggests comparable physicochemical properties of
      DQ2 and DQ8 but are widely different from DQ6. In 1984, the conclusion was that
      molecular cloning of the genes for the autoantigens, antibodies, T-cell
      receptors, as well as HLA class I and II molecules associated with diabetes are
      essential for analysing the components which control the development of
      pancreatic beta-cell autoimmunity. In 1994, autoantigens and HLA molecules have
      been cloned and recombinant reagents developed to be used in experiments aimed at
      testing whether it will be possible to predict IDDM.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7821744
TI  - On the pathogenesis of IDDM.
AB  - A model of the pathogenesis of insulin-dependent diabetes mellitus, i.e. the
      initial phase of beta-cell destruction, is proposed: in a cascade-like fashion
      efficient antigen presentation, unbalanced cytokine, secretion and poor beta-cell
      defence result in beta-cell destruction by toxic free radicals (O2- and nitric
      oxide) produced by the beta cells themselves. This entire process is under
      polygenetic control.

PMID- 7821747
TI  - The care and feeding of structural biologists.

PMID- 7821745
TI  - IDDM: an islet or an immune disease?
AB  - Insulin-dependent diabetes develops as a consequence of the selective destruction
      of insulin-producing cells by an autoimmune reaction. However, the precise series
      of events which trigger anti-islet autoreactive T cells is still being
      investigated. Major issues will need to be raised before a comprehensive view of
      the anti-islet autoimmune reaction can be delineated. These include defining the
      primary site of activation of autoreactive lymphocytes and exploring hypotheses
      to explain the chronicity of the diabetes process. These issues all relate with
      the more general dilemma of the actual role of the islets of Langerhans in
      breaking self tolerance to beta-cell antigens. By studying non-obese diabetic
      mice deprived of beta cells following a single injection of a high dose of
      alloxan at 3 weeks of age, we recently obtained evidence that the activation of
      autoreactive T cells requires the presence of target islet cells in order to
      develop.

PMID- 7821746
TI  - Does C-peptide have a physiological role?
AB  - Short-term administration of physiological amounts of C-peptide to patients with
      insulin-dependent diabetes was found to reduce the glomerular hyperfiltration in
      these patients as well as augment whole body glucose utilization. It could also
      be shown that C-peptide administration increases blood flow, oxygen uptake and
      capillary diffusion capacity of exercising forearm muscle in IDDM patients,
      probably by increasing capillary recruitment in the working muscle. Studies under
      in vitro conditions have shown that C-peptide stimulates glucose transport in
      skeletal muscle with its maximal effect within the physiological concentration
      range. The findings in a clinical study in which IDDM patients were given C
      peptide and insulin or insulin alone for 4 weeks in a double-blind randomized
      study design, indicate that C-peptide improves renal function by reducing urinary
      albumin excretion and glomerular filtration, decreases blood retinal barrier
      leakage and improves metabolic control. Preliminary findings suggest that C
      peptide administration on a short-term basis (3h) may ameliorate autonomic
      neuropathy by restoring to near normal the heart rate variability in response to
      expiration and inspiration. Insight into a possible mechanism of action of C
      peptide is provided by the finding that C-peptide stimulates Na+K(+)-ATPase
      activity in renal tubular segments. In conclusion, the present results suggest
      that, contrary to the prevailing view, C-peptide possesses important
      physiological effects.

PMID- 7821748
TI  - Intramolecular signaling upon complexation.
AB  - Crystal habits can be used as indicators of conformational changes in their
      constituent proteins. As in the conversion of unliganded hemoglobin to the
      oxygenated form, the addition of a small hapten to a suspension of platy crystals
      of an unliganded Fab (NC6.8) results in the immediate disintegration of the
      plates and their replacement with prisms of the ligand-protein complex.
      Examination of the native and liganded forms by X-ray crystallography reveals
      that the space groups and protein structures are different. During complexation
      there are ligand-induced conformational changes both in the antigen combining
      site (local alterations) and in more distal portions of the molecule (allosteric
      changes). There is an extension of the light chain (10 A increase in length), a
      commensurate shortening of the heavy chain (by flexing), and a decrease in the
      "elbow bend" angle of 31 degrees (184 degrees to 153 degrees). Relative to the
      variable domains, the constant domain pair moves mainly as a unit in such a way
      that the carboxyl end of the heavy chain is displaced by 19 A. In an intact
      antibody this displacement may be relayed as a tug (by tensile forces) on the
      segment connecting the Fab to the Fc region, perhaps altering the orientations of
      the constituents responsible for such effector functions as complement
      activation.

PMID- 7821749
TI  - Structure of an anti-idiotypic Fab against feline peritonitis virus-neutralizing
      antibody and a comparison with the complexed Fab.
AB  - The crystal structure of anti-idiotopic Fab 409.5.3, made against an E2 specific
      feline infectious peritonitis virus-neutralizing antibody 730.1.4, has been
      determined in its free from, at 2.9 A resolution by molecular replacement. This
      antibody, used as an immmunogen, elicits the production of anti-anti-idiotypic
      antibodies that in turn neutralize the virus. The structure of the uncomplexed
      Fab was refined using constrained-restrained least squares minimization and
      simulated annealing in combination with conjugate gradient techniques to a
      crystallographic R of 0.22 based on 16,482 unique reflections between 20.0 and
      2.9 A. The free antiidiotypic Fab shows, when compared to its complexed form, a 5
      degrees rotation of its variable light with respect to its variable heavy domain
      and rearrangement of complementarity determining region loops, which permits
      optimization of the stereocomplementarity between interacting molecules. This
      finding supports the induced fit hypothesis for antibody antigen interaction.

PMID- 7821750
TI  - Oligosaccharide-protein interactions in IgG can modulate recognition by Fc gamma
      receptors.
AB  - X-ray crystal structures of IgG-Fc provide evidence of extensive noncovalent
      interactions between the protein and carbohydrate moieties, and glycosylation, at
      Asn-297 within the Fc, has been shown to be important for effector functions
      mediated through Fc gamma receptors expressed on leukocytes. We have applied
      protein engineering in an attempt to define protein/carbohydrate interactions
      essential to wild-type biological activity. We demonstrate that replacement of
      Lys-246, Asp-249, and Glu-258, which make contacts with GlcNac and Gal on the
      outer alpha[1-->6] arm, do not affect recognition of human chimeric IgG3 by human
      Fc gamma RI and Fc gamma RII. However, replacement of Asp-265, which make
      contacts with the primary GlcNac sugar residue and is covalently attached to Asn
      297, resulted in loss of recognition of both Fc gamma RI and Fc gamma RII.
      Similarly, replacement of Asp-265 in mouse IgG2b resulted in loss of recognition
      by mouse Fc gamma RII. These results suggest that noncovalent contacts of Asp-265
      with the primary GlcNac residue are important for maintenance of recognition of
      IgG by Fc gamma receptors whereas contacts with GlcNac and Gal on the alpha [1-
      >6] arm do not have a measurable effect. This conclusion was supported by
      experiments in which galactose-deficient and fully galactosylated forms of a
      human IgG4-Fc fragment were shown to be equivalent in their ability to inhibit
      superoxide generation by IgG4 stimulated U937 cells.

PMID- 7821751
TI  - NMR observation of interactions in the combining site region of an antibody using
      a spin-labeled peptide antigen and NOESY difference spectroscopy.
AB  - A spin-labeled peptide antigen (TEMPOVEVPGSQHIDSQ) was used to measure NOESY
      difference spectra that show interactions in the binding site region of the Fab
      fragment of the anti-cholera toxin peptide antibody TE33. In addition to
      identification of peptide-Fab interactions and interactions within the bound
      peptide, these difference spectra show well-resolved cross peaks due to
      interactions within the large Fab fragment (50 kDa). These difference spectra
      indicate that the conformational changes in the Fab upon peptide binding are
      confined to the combining site region of the antibody. The NOESY difference
      spectra of selectively deuterated Fab molecules were used in combination with
      HOHAHA measurements to assign the interactions to amino acid type and to identify
      the interactions within the Fab as either inter- or intraresidue interactions.
      The assignment of interactions within the Fab to corresponding aromatic residues
      in the Fab sequence was facilitated by an earlier NMR-derived model calculated on
      the basis of NOE restraints on Fab-peptide and intra-bound-peptide distances. The
      new restraints on distances within the Fab, combined with the previously obtained
      restraints, were used to generate a refined NMR-derived model for the TE33
      peptide complex.

PMID- 7821752
TI  - Identification of specificity-determining residues in antibodies.
AB  - The successful identification of the residues that contact ligand has important
      implications, especially in view of the increasing use of antibodies in various
      medical and industrial applications. Analysis of the crystallographically
      derived, three-dimensional structures of five antibody-antigen complexes and of
      the available amino acid sequence data on antibody variable regions reveals that
      the residues that contact antigen are in the main also the most variable. It is
      proposed that a good first guess of the identity of the specificity-determining
      residues can be made from an examination of the variability values at sequence
      positions. New boundaries for the complementarity-determining regions are
      proposed.

PMID- 7821753
TI  - Beta PDGFR-IgG chimera demonstrates that human beta PDGFR Ig-like domains 1 to 3
      are sufficient for high affinity PDGF BB binding.
AB  - To localize human beta PDGFR binding determinants, we constructed a fusion
      protein comprising beta PDGFR Ig-like domains 1 to 3 and an IgG1 Fc domain (beta
      PDGFR-HFc). beta PDGFR-HFc was expressed as a 200 kDa dimeric molecule and
      contained Fc epitopes as demonstrated by anti-mouse Fc antibody recognition.
      Scatchard analysis revealed that PDGF BB possessed a dissociation constant of 1.5
      nM for beta PDGFR-HFc. Thus, beta PDGFR Ig-like domains 1 to 3 are sufficient for
      high affinity PDGF BB binding. We exploited this fusion protein technology to
      identify and characterize beta PDGFR antagonists using a sensitive beta PDGFR
      immunosorbent assay. In this assay, beta PDGFR-HFc half-maximally bound to PDGF
      BB with an affinity of around 150 pM. Suramin, as well as bacterially expressed
      and refolded human alpha PDGFR domains 1-3, inhibited beta PDGFR-HFc binding to
      PDGF BB half-maximally at 25 microM and 10 nM respectively. Therefore, alpha
      PDGFR D1-3, like beta PDGFR D1-3, are sufficient for high affinity PDGF BB
      binding. Furthermore, the beta PDGFR-HFc immunosorbent assay will be useful to
      identify beta PDGFR antagonists as well as to study alpha and beta PDGFR
      substitution mutants which further map receptor binding determinants.

PMID- 7821754
TI  - Milestones in structural immunology.

PMID- 7821755
TI  - A structural view of CD4 and CD8.
AB  - CD4 and CD8 are cell-surface glycoproteins that participate in molecular
      complexes involved in both T cell development and antigen recognition by T cells.
      CD4 and CD8 interact with nonpolymorphic regions of class II and class I major
      histocompatibility complex (MHC) molecules, respectively, and these interactions
      result in increased intercellular adhesion and enhanced stimulation of T cells. A
      src-like tyrosine kinase, p56lck, is associated with the cytoplasmic domain of
      both CD4 and CD8 and may be involved in transmembrane signaling. Crystal
      structures of extracellular regions of CD4 and CD8 have been determined and have
      provided a basis for understanding and probing CD4 and CD8 function. The
      structures of CD4 and CD8 are reviewed here, along with the implications of these
      structures for CD4 and CD8 function.

PMID- 7821756
TI  - Structural studies of class I major histocompatibility complex proteins: insights
      into antigen presentation.
AB  - The three-dimensional structures of three human and two murine class I molecules,
      in complex with single peptides and with mixtures of endogenous peptides, have
      now been determined to high resolution. These structures have afforded important
      insights into the way in which antigenic peptides are bound by an MHC class I
      molecule, and how a given MHC molecule can bind a large number and variety of
      peptides, for presentation to a T cell receptor. Peptides are bound in a cleft
      located in the alpha 1/alpha 2 domain of a class I molecule. They are tethered by
      an array of hydrogen bonding interactions many of which are conserved among the
      different structures. Binding is also accomplished through van der Waals
      interactions between two or three peptide residues and complementary pockets in
      the cleft. The location and the characteristics of its pockets are unique to a
      given MHC class I molecule, and so determine the identity of the anchor residues
      of the set of peptides that bind. The antigenic epitope recognized by the TCR
      consists of residues on the MHC as well as the side chains of those peptide
      residues that point out from the cleft. The various strategies used to expand the
      repertoire of peptides bound and presented are discussed.

PMID- 7821757
TI  - Antigenic peptides.
AB  - Although most short, linear peptide fragments of proteins are unstructured in
      aqueous solution, a number of immunogenic and antigenic peptides have been shown
      to have conformational preferences for structured forms. By using mainly NMR and
      CD spectroscopy, it has been possible to detect and quantify quite small
      populations of beta-turn, helical, and nascent helical conformations. Recent
      studies have been published indicating that the presence of structured forms is
      correlated with the location of T cell and/or B cell epitopes in peptide
      sequences. X-ray crystal structures of complexes between peptides and anti
      peptide antibodies frequently show the peptides bound in beta-turn conformations,
      and the presence of helix in one peptide-antibody complex has been shown by NMR
      spectroscopy. Studies of peptides free in solution and bound to anti-peptide
      antibodies in the crystal indicate that the structure of the principal
      neutralizing determinant of HIV-1 probably includes at least one beta-turn in a
      highly conserved region. These results can potentially be used in the design of
      peptide-based vaccines.

PMID- 7821758
TI  - Anti-idiotypic antibodies: biological function and structural studies.
AB  - Under a variety of circumstances antibodies can be elicited against the variable
      region of other antibody molecules (anti-idotypic antibodies, anti-ids). Some of
      the antibodies are directed against the binding sites of the eliciting
      antibodies. Of particular interest are the antibodies that recognize epitopes of
      the original antibody that are in contact with antigen. Antibodies of this kind
      have been produced and used in a variety of situations including attempts at
      using them as therapeutic agents. In recent years structural data at the atomic
      level have emerged for anti-idiotypic antibodies from X-ray diffraction studies.
      These studies provided structural basis for molecular mimicry of anti-ids. For a
      large globular antigen (lysozyme), where epitope is noncontinuguous, molecular
      mimicry is not present at the atomic level. In this case, idiotopes are largely
      composed of CDR residues, but framework residues are also used. For an epitope
      that is sequence-specific (anti-FIPV system), molecular mimicry appears to be
      present as evidenced by the sequence homology between the CDR loops of the anti
      id and the epitope of the original antigen. In the case of a small hormone
      antigen (angiotensin II), an internal image of the eliciting antigen appears to
      be represented in a single CDR loop of the antiiodiotypic antibody.

PMID- 7821759
TI  - Cytokines and their receptor complexes.
AB  - The 3-dimensional structures that resulted from X-ray diffraction and nuclear
      magnetic resonance analyses of a variety of cytokines are reviewed. These
      proteins form distinct, well-defined superfamilies based on the structures of
      their monomers, even in the absence of significant sequence homology. However, in
      several cases, where the active form of a cytokine is a dimer or higher oligomer,
      these similar monomers adopt very different modes of dimerization. Two examples
      of complexes of cytokines with receptor molecules are described and the
      implications for signal transduction are discussed.

PMID- 7821760
TI  - Three-dimensional structures of alpha and beta chemokines.
AB  - Members of the chemokine family of proteins play a key role in the orchestration
      of the immune response. This family has been further divided into two
      subfamilies, alpha and beta, based on sequence, function, and chromosomal
      location. To date, the three-dimensional structures of two members of the alpha
      subfamily, interleukin-8 (IL-8) and platelet factor 4, and one member of the beta
      subfamily, human macrophage inflammatory protein-1 beta (hMIP-1 beta), have been
      solved by either NMR or X-ray crystallography. In this review, we discuss their
      three-dimensional structures and their possible relationship to function. The
      structures of the monomers are very similar, as expected from the significant
      degree of sequence identity between these proteins. The quaternary structures of
      the alpha and beta chemokines, however, 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. Platelet
      factor 4 is a tetramer comprising a dimer of dimers of the IL-8 type. The IL-8
      dimer comprises a six stranded anti-parallel beta-sheet, three strands
      contributed by each subunit, on top of which lie two antiparallel helices
      separated by approximately 14 A, and the symmetry axis is located between
      residues 26 and 26' (equivalent to residue 29 of hMIP-1 beta) at the center of
      strands beta 1 and beta 1'.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7821761
TI  - Structural immunology: problems in molecular recognition.

PMID- 7821762
TI  - Single-chain Fvs.
AB  - Single-chain Fvs (sFvs) are recombinant antibody fragments consisting of only the
      variable light chain (VL) and variable heavy chain (VH) domains covalently
      connected to one another by a polypeptide linker. Due to their small size, sFvs
      have rapid pharmacokinetics and tumor penetration in vivo. Single-chain Fvs also
      show a concentration-dependent tendency to oligomerize. Bivalent sFvs are formed
      when the variable domains of a sFv disassociate from one another and reassociate
      with the variable domains of a second sFv. Similar rearrangement and
      reassociation of variable domains from different sFvs can result in the formation
      of trimers or higher multimeric oligomers. Each Fv in a bivalent or multivalent
      Fv is composed of the VL domain from one sFv and the VH domain from a second sFv.
      Modifying linker length or the inclusion of antigen may stabilize the VL/VH
      interface against rearrangement such that specific multimeric or monomeric forms
      of sFvs may be isolated. Nuclear magnetic resonance studies have shown that
      McPC603-derived Fv and sFvs have similar structures, and that the sFv linker is a
      rapidly moving, highly flexible peptide with a random coil-like structure. In X
      ray crystallographic investigations of three different sFvs, linkers have also
      been found to be disordered. Indirect evidence suggests that a monomeric sFv has
      been crystallized in one case, and dimeric sFvs in the other two.

PMID- 7821763
TI  - Preferential expression of CD30 by human CD4+ T cells producing Th2-type
      cytokines.
AB  - A large panel of human CD4+ T helper (Th) cell clones with established Th1, Th2,
      or Th0 profiles of cytokine secretion were examined for the expression of CD30, a
      member of the tumor necrosis factor receptor superfamily. Th1 clones expressed
      poor or no CD30 mRNA, and showed low or undetectable expression of both membrane
      and soluble CD30 (sCD30) protein, whereas Th2 clones showed both CD30 mRNA and
      membrane CD30 and released substantial amounts of sCD30. Th0 clones exhibited an
      intermediate pattern of CD30 expression and release. When T cells from the same
      donor were stimulated with three different antigens (purified protein derivative,
      PPD; Toxocara canis excretory/secretory antigen, TES; Lolium perenne group I, Lol
      p I), production of high concentrations of IFN-gamma, but not expression of CD30
      or production of IL-4 and IL-5, were observed at any time after stimulation with
      PPD. In contrast, both CD30 expression and production of IL-4 and IL-5, but not
      of IFN-gamma, were concomitantly detectable in TES- and Lol p I-reactive T cells,
      suggesting a temporal relationship between CD30 expression and beginning of Th2
      type cytokine production. Finally, CD4+CD30+ T cells specific for Lol p I and
      inducible to production of Th2-type cytokines were sorted out from the
      circulation of grass-sensitive patients in concomitance with the onset of
      allergic symptoms during the seasonal exposure to grass pollen. Thus, CD30
      expression appears to be associated with the differentiation/activation pathway
      of human T cells producing Th2-type cytokines.

PMID- 7821764
TI  - Analysis of antigenic surfaces of proteins.
AB  - The processes underlying molecular evolution have proved difficult to understand
      due to the complexity and obscurity of the selective pressures at work. The
      strong selective pressure to optimize antigen recognition means that antibody
      paratopes are more favorable systems than most in which to investigate these
      processes, as are viral epitopes, which evolve under an inverse pressure, rapidly
      changing to avoid recognition. Because recognition is a property of the surfaces
      of these molecules we expect that their evolutionary development may be read in
      the changes in the 3-dimensional array of chemical groups displayed on their
      surface. We have analyzed the bulk properties of these surfaces and find that
      there are significant differences in exposed amino acid preferences among 1) a
      control group of immunologically secluded proteins, 2) binding surfaces of
      immunoglobulins, and 3) the outer surfaces of picornaviruses. Compared to the
      control group, the immunoglobulin complementarity determining regions possess a
      relative excess of serine residues whereas picornaviruses suppress serine but
      overuse threonine residues, suggesting that the differing selective pressure has
      led to perturbations in the population of amino acid types on the surface of
      these proteins. Although these changes may be rationalized in terms of the
      structure and chemistry of the different side chains, we suggest that there may
      be a further, genetic component behind the observations: point mutations in the
      respective codons for serine and threonine lead to markedly different forms of
      structural variability. The high rate of reselection observed for these residues
      is in line with this second mechanism.

PMID- 7821765
TI  - Structural features of the reactions between antibodies and protein antigens.
AB  - Antibodies bind protein antigens over large sterically and electrostatically
      complementary surfaces. Van der Waals forces, hydrogen bonds, and occasionally
      ion pairs provide stability to antibody-antigen complexes. In addition, water
      molecules contribute hydrogen bonds linking antigen and antibody, and increase
      the complementarity of antigen-antibody interfaces. In qualification to a strict
      'lock and key' mechanism, evidence of conformational changes between free and
      complexed antibodies indicate some accommodation to the antigen. Antibody-protein
      antigen reactions are enthalpically driven with varying degrees of entropic
      compensation, often dependent on the magnitude of the enthalpy of the reaction.
      In the case of two antibody-combining sites studied by X-ray diffraction, the
      relative arrangements of the variable domains of the light and heavy chains of
      the antibody change slightly from the free to the antigen-bound state.
      Furthermore, the contacting residues of both antibodies exhibit similar reduced
      mobilities when complexed to antigen, suggesting that differences in 'solvent
      entropy' rather than in conformational freedom may be the source of different
      entropic compensation factors. In concert, data from structural studies, reaction
      rates, calorimetric measurements, molecular dynamics simulations, and site
      directed mutagenesis are beginning to detail the nature of antibody-protein
      antigen interactions.

PMID- 7821766
TI  - Metalloantibody design.
AB  - Metal-binding sites were designed within the antigen-binding pocket of the
      catalytic antibody 43C9 based on a 3-dimensional antibody model and
      crystallographic structures of Zn-binding metalloenzymes. These tetrahedral Zn
      binding sites were designed to mimic both secondary and tertiary structural
      characteristics of catalytic metal sites in enzymes. Each site was planned to
      have two His ligands across from each other on adjacent antiparallel beta
      strands. Sites were selected to sequester the metal ion from bulk solvent and
      place an open metal coordination position next to the antigen or potential
      substrates. Three distinct metal-site designs, with ligands in the variable light
      domain, in the variable heavy domain, and in both domains, were later implemented
      experimentally and shown spectroscopically to bind metal ions as predicted. These
      results demonstrate the success of our design approach, the versatility of the
      antibody structure for metalloprotein design, and the validity of the 3
      dimensional model. The ability to predictably design multiple metal sites in the
      ordered antigen-recognition region at the bottom of the pocket allows tuning of
      metal ion placement and enhances the likelihood of interaction with putative
      substrates.

PMID- 7821767
TI  - Isolation of growth hormone and in vitro translation of mRNA isolated from
      pituitaries of the gilthead sea bream Sparus aurata.
AB  - Growth hormone (GH) polypeptide was purified from pituitary glands of the
      gilthead sea bream (Sparus aurata) by a two-step procedure involving gel
      filtration on Sephadex G-100 and reverse-phase high-performance liquid
      chromatography (rpHPLC). At each stage of purification, fractions were monitored
      by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and by immunoblotting using
      anti-bonito GH antiserum. The molecular weight of the sea bream GH was estimated
      by SDS-PAGE to be 21 kDa when electrophoresed in the absence of beta
      mercaptoethanol (nonreduced conditions) and 22 kDa when electrophoresed under
      reduced conditions (in the presence of 1% beta-mercaptoethanol). Pituitary RNA
      was used to direct cell-free translation. When specific immunoisolation from 35S
      labeled proteins was conducted, using antisera against Sparus or tilapia GH, a
      larger prehormone was immunoprecipitated. The size of the pre-GH was estimated to
      be 27-28 kDa under reduced conditions and 26-27 kDa under nonreduced conditions,
      in agreement with the calculated molecular weight of Sparus pre-GH of 26,296
      based on the deduced amino acid sequence of Sparus GH cDNA. The specificity of
      the immunoprecipitation reaction was demonstrated by the ability of recombinant
      tilapia GH to compete with the radioactively labeled translation product. No such
      competition was found after the addition of BSA. Our results demonstrate that the
      sea bream GH is similar in its size to other purified fish GHs and provide direct
      evidence for the synthesis of GH as a prepeptide, thus supporting the conclusions
      presented earlier by GH cDNA cloning.

PMID- 7821769
TI  - Episodic growth hormone secretion in the grass carp, Ctenopharyngodon idellus (C.
      & V.).
AB  - The secretory pattern of growth hormone (GH) was studied in sexually immature
      grass carp (0.5-1.0 kg body wt). Serial blood samples were taken at 15-min
      intervals during 4- to 6-hr sampling periods via a dorsal aorta cannula. During
      each 4- to 6-hr sampling period plasma GH profiles demonstrated episodic
      secretion. Two patterns were observed, consisting either of one episodic of GH
      secretion (single or several pulses clustered) or two episodes of GH secretion
      during each sampling period. The interval between the two episodes of GH
      secretion was 2.6 hr. This is the first demonstration of episodic GH secretion in
      a teleost.

PMID- 7821768
TI  - Active immunization with vasoactive intestinal peptide prevents the secretion of
      prolactin induced by electrical stimulation of the turkey hypothalamus.
AB  - Immunoneutralization of endogenous vasoactive intestinal peptide (VIP) by active
      immunization with chicken VIP (cVIP) reduced both basal circulating prolactin
      (PRL) and steady-state levels of pituitary PRL mRNA in the turkey. This
      immunoneutralization severely curtailed the plasma PRL response induced by
      infusion of cVIP into the median eminence, and totally blocked the plasma PRL
      release effected by electrical stimulation of the medial preoptic nucleus. This
      is the first demonstration that a stimulated PRL secretion can be blocked by
      neutralizing VIP availability. These findings imply that among the neurochemicals
      released by electrical stimulation, only VIP directly stimulates PRL secretion.
      In addition to serving as a PRL releasing factor, VIP also appears to be involved
      in the regulation of pituitary PRL mRNA expression.

PMID- 7821770
TI  - Seasonal changes of plasma prolactin concentration in the reproduction of the
      crested newt (Triturus carnifex Laur).
AB  - Plasma prolactin (PRL) and vitellogenin (VTG) concentrations were determined
      during the annual reproductive cycle of the newt Triturus carnifex Laur. Plasma
      PRL was measured by a radioimmunoassay using purified newt (Cynops pyrrogaster)
      PRL as standard and radioligand and its antibodies. Using ELISA, plasma VTG
      titers were related to ovarian weight. The trends in PRL differed in the two
      sexes: the PRL changes seemed to be related with vitellogenic processes in the
      female, whereas they were more related to reproductive behavior in the male.

PMID- 7821771
TI  - The corticosteroidogenic response of brown and rainbow trout alevins and fry to
      environmental stress during a "critical period".
AB  - Postemergent salmonid fry experience a "critical period" in their development,
      during which there may be a high mortality rate, so determining the long-term
      success of the year class. The mechanism(s) underlying this phenomenon are not
      fully understood but physiological stress may be a contributory factor. This
      study sought to establish at what point in their development, posthatch,
      salmonids become stress responsive in terms of activation of the hypothalamic
      pituitary-interrenal (HPI) axis. Immunoreactive corticosteroids were measured in
      tissue extracts of rainbow trout at intervals from 4 weeks prehatch to 27 weeks
      posthatch and in brown trout from 5 to 22 weeks posthatch. Corticosteroids were
      detectable throughout this period in both species. Simultaneous determination of
      whole-body immunoreactive corticosteroid levels (IRC) and plasma cortisol levels
      in fingerling trout validated the use of whole-body levels as an indicator of
      stress-induced elevation of corticosteroids. However, the dynamics of the
      circulating cortisol response to stress were not fully conveyed by whole-body
      measurements. From 5 weeks posthatch IRC increased significantly within 30-60 min
      following mechanical disturbance and confinement, suggesting a functional HPI
      axis to be present. An ectoparasite (Ichthyobodo sp.) infestation during this
      period caused a substantial increase in IRC levels in both species indicating
      that the HPI axis in these fish was sensitive to naturally occurring stressors.
      The response of fry to acute and chronic stress resembled that of adult fish in
      terms of duration. These data indicate that the early pre- and postemergent
      stages of salmonid fish are likely to be able to benefit from the adaptive
      advantage of HPI activation during episodes of acute stress but may also be
      susceptible to the deleterious consequences of prolonged activation of the HPI
      axis under conditions of chronic stress.

PMID- 7821772
TI  - Effects of lamprey gonadotropin-releasing hormone-III on steroidogenesis and
      spermiation in male sea lampreys.
AB  - The biological activities of lamprey gonadotropin-releasing hormone-III (GnRH
      III) were determined in the adult male sea lamprey, Petromyzon marinus. One
      injection of lamprey GnRH-III at 0.1 or 0.2 microgram/g body wt stimulated plasma
      estradiol and progesterone levels in adult male sea lampreys undergoing final
      maturation. Four successive injections of lamprey GnRH-III at 0.1 microgram/g of
      lamprey GnRH-1 at 0.2 microgram/g induced spermiation in 78 or 30% of the
      lampreys, respectively, compared to 0% in controls by Day 16. In summary, lamprey
      GnRH-III is biologically active in stimulating the pituitary-gonadal axis in
      adult male lampreys.

PMID- 7821773
TI  - Salmon gonadotropin-releasing hormone and gonadotropin are involved in precocious
      maturation induced by photoperiod manipulation in underyearling male masu salmon,
      Oncorhynchus masou.
AB  - The relationship between gonadal maturation, salmon gonadotropin-releasing
      hormone (sGnRH), and gonadotropin (GTH) subunit contents in the brain and
      pituitary was investigated in underyearling masu salmon, Oncorhynchus masou.
      Gonadal maturation was manipulated by changing photoperiod to examine the
      involvement of these hormones in this process. Fish were divided into short (8 hr
      L: 16 hr D) and long photoperiod (16 hr L:8 hr D) groups in mid-June and
      maintained for 4 months until October. Gonadal maturation occurred in most males
      (precocious males), while a few remaining males and all females did not mature
      throughout the experiment irrespective of photoperiodic group. In precocious
      males, pituitary contents of sGnRH, GTH I beta, and GTH II beta increased faster
      under short photoperiod than under long photoperiod, and spermiation was observed
      in August. Under long photoperiod, these hormones gradually increased until
      October when spermiation occurred. sGnRH concentrations in the telencephalon of
      precocious males were high when spermiation occurred; in August, they were higher
      in the short photoperiod than in the long photoperiod group; in October, they
      were higher in the long photoperiod group. The increases of sGnRH and GTH in the
      pituitary and sGnRH in the brain appear to be involved in precocious maturation
      inducible by manipulation of photoperiod.

PMID- 7821774
TI  - Activation of salmon gonadotropin-releasing hormone synthesis by 17 alpha
      methyltestosterone administration in yearling masu salmon, Oncorhynchus masou.
AB  - Juvenile salmonid pituitary gonadotropin (GTH) contents are elevated after
      steroid hormone treatment, but the involvement of gonadotropin-releasing hormone
      (GnRH) is unclear. Activation of salmon GnRH (sGnRH) synthesis by 17 alpha
      methyltestosterone (MT) administration has been examined in the brain of yearling
      masu salmon (future precocious males and immature females) using an in situ
      hybridization technique combined with radioimmunoassay. Oral MT application
      markedly increased pituitary GTH II beta, but not GTH I beta, contents in both
      sexes. In future precocious males, MT treatment increased the number of cells
      expressing sGnRH mRNA in the preoptic area about threefold, whereas there were no
      significant differences in the olfactory bulbs and the ventral telencephalon. No
      significant changes were observed in cell sizes nor the numbers of silver grain
      per 100 microns2 cell in any of the brain regions. Thus, in future precocious
      males, preoptic sGnRH neurons may be activated by sex steroids. In contrast, no
      significant changes were observed in sGnRH mRNA levels of immature females after
      MT treatment. These differences in responses to sex steroids of sGnRH cells in
      the preoptic area between future precocious males and immature females suggest
      that MT has indirect actions via sGnRH and/or direct actions on the pituitary in
      the former, and that MT acts directly on the pituitary in the latter.

PMID- 7821775
TI  - Calcitonin gene-related peptide relaxes cholecystokinin-induced tension in Iguana
      iguana gallbladder strips.
AB  - The presence of a calcitonin gene-related peptide (CGRP)-like material was
      demonstrated in the iguana, Iguana iguana, gallbladder using immunocytochemistry.
      An intense reaction was observed in nerves located in the smooth muscle layers
      and associated blood vessels but no immunoreactive cell bodies were found. In
      vitro tension studies using gallbladder strips showed that chicken CGRP was more
      potent in relaxing cholecystokinin-induced tension than either human or rat CGRP.
      The use of glibenclamide and L-NG-nitro-arginine methyl ester suggested that this
      relaxation is mediated by either nitric oxide release from nerves stimulated by
      CGRP or by CGRP acting directly on the gallbladder smooth muscle.

PMID- 7821776
TI  - Characterization of crustacean hyperglycemic hormone from the crayfish
      (Procambarus clarkii): multiplicity of molecular forms by stereoinversion and
      diverse functions.
AB  - The complete amino acid sequence of two forms of crustacean hyperglycemic hormone
      (CHH) from the X-organ sinus gland complex of crayfish (Procambarus clarkii) has
      been determined. There are two variants of P. clarkii CHH (Prc-CHH), I and II,
      which can be separated by reversed-phase high-performance liquid chromatography
      (RP-HPLC). Each variant was oxidized by performic acid and then cleaved with
      lysyl endopeptidase. Intact hormone was also digested with trypsin and
      endoproteinase Asp-N, successively. The resulting fragments were separated by RP
      HPLC and subjected to sequence analyses by a gas-phase sequencer and tandem mass
      spectrometry. Both variants contain 72 amino acid residues with three disulfide
      linkages, at positions 7-43, 23-39, and 26-52, and differ from each other by the
      D/L epimerization of phenylalanine at position 3; Prc-CHH-II contains D-amino
      acid. Injections of Prc-CHH-I and Prc-CHH-II at a dose of 12.5 pmol resulted in
      significant increase of hemolymph glucose levels in the crayfish. The hormones
      are also active in repressing ecdysteroid synthesis at concentrations of 250 mM
      (Prc-CHH-I) and 25 nM (Prc-CHH-II) in Y-organ culture. These results may indicate
      that the stereoinversion in the CHH molecule leads to an important alternation in
      hormonal functions during crustacean development.

PMID- 7821777
TI  - Binding characteristics of an androgen receptor in the ovaries of coho salmon,
      Oncorhynchus kisutch.
AB  - Androgen receptors were identified in the cytosol from ovaries of juvenile coho
      salmon, Oncorhynchus kisutch. The binding for the synthetic androgen mibolerone
      was specific and saturable (Kd = 0.32 +/- 0.02 nM; Bmax = 15.31 +/- 4.31 fmol/mg
      protein). Bound [3H]mibolerone was much higher in ovarian cytosol than in
      cytosolic extracts from heart, liver, and muscle. [3H]mibolerone specific binding
      was 50% lower in the plasma than in the ovarian cytosolic extracts.
      [3H]mibolerone binding was displaced most effectively by those 17 alpha
      methylated synthetic androgens (mibolerone, methyltestosterone,
      methylandrostanolone) that can induce functional masculinization in fish. The
      naturally occurring androgens 11-ketotestosterone and 5 alpha-dihydrotestosterone
      both displaced [3H]mibolerone binding, but they were 10- to 100-fold less
      effective than the 17 alpha-methylated androgens. Testosterone, 11 beta
      hydroxyandrostenedione, estradiol, progesterone, and 17 alpha,20 beta
      dihydroxyprogesterone were not potent competitors. [3H]mibolerone specific
      binding was reduced after preincubation with trypsin. About 25% of the binding in
      the cytosolic extract had DNA binding affinity under experimental conditions. The
      characteristics of this androgen binding site are consistent with a model of
      receptor-mediated steroid-induced sex inversion.

PMID- 7821778
TI  - The effect of environmental temperature on episodic growth hormone release of
      meat-type chickens selected for 6 week body weight or for improved feed
      efficiency between 3 and 6 weeks of age.
AB  - The effect of a high (33 degrees C) compared to a normal (23 degrees C) ambient
      temperature on the pulsatile release of growth hormone (GH) has been studied in 4
      week-old, cannulated male meat-type chickens selected for high body weight (GL
      line) or for improved feed efficiency (FC line). When reared in the normal
      temperature environment, overall circulating mean and amplitude GH values of FC
      chickens were significantly higher than those of GL chickens. There were no
      differences in GH pulse length or frequency between genotypes. The high rearing
      temperature completely abolished the pulsatility of GH in the plasma in both
      lines, but without affecting overall mean GH levels.

PMID- 7821779
TI  - Influence of gonadectomy and steroid hormone replacement therapy on the
      gonadotropin-releasing hormone neuronal system in the anterior preoptic area of
      the frog (Rana esculenta) brain.
AB  - Effects of gonadectomy and sex steroid replacement therapy were studied on the
      anterior preoptic area-located GnRH-immunoreactive neurons in males and females
      of the frog, Rana esculenta. Removal of gonads caused a drastic reduction in the
      immunostaining as well as in the number of GnRH neurons in the anterior preoptic
      area of the brain in both sexes. Replacement therapy with estradiol-17 beta,
      testosterone, and 5 alpha-dihydrotestosterone, given alone or in combination,
      enhanced the somal accumulation of immunoreactive material in GnRH neurons and
      also their number. These effects, however, varied to some extent from steroid to
      steroid, a combination of testosterone and 5 alpha-dihydrotestosterone being most
      effective in gonadectomized males, whereas that of estradiol-17 beta and
      testosterone was most effective in gonadectomized females. The present data are
      the first to demonstrate that androgen and estrogen can influence the
      immunoreactive GnRH neurons in the anterior preoptic area of the amphibian brain.

PMID- 7821780
TI  - Ultrastructural features of neurosecretory cells in the medulla externa of the
      crayfish eyestalk.
AB  - A conglomerate of 8-12 neurons in the medulla externa of the crayfish eyestalk
      was explored in their reaction to a polyclonal antibody against the tyrosinated
      octapeptide Red Pigment Concentrating Hormone (Tyr-RPCH). These are large neurons
      with diameters within a range of 33-43 microns and they were all positively
      stained with neutral red. By intracellular staining with lucifer yellow, the
      neurons were found to branch extensively within the medulla externa and the
      lamina ganglionaris of the eyestalk. Each neurite bifurcates at about 40 microns
      from the soma. Both branches run to the medial edge of the eyestalk; one proceeds
      distally to the lamina ganglionaris, while the other runs proximally to the
      medulla interna. Both end freely in multiple arborizations, covering from the
      medial to the lateral edges of the eyestalk. No branches were found to the sinus
      gland, the main neurohaemal organ of the eyestalk. A group of 4 neurons in the
      conglomerate consistently rendered positive reaction to the anti-Tyr-RPCH
      antibody (A-RPCH). They are superficially located in the cluster, and at the
      electron microscope, they showed the usual features of a secretory cell, i.e.,
      clear and dense granules, an active and well-developed Golgi apparatus, and rough
      endoplasmic reticulum. The dense granules were larger (mean diameter: 101.5 nm)
      than the clear granules (mean diameter: 90.3 nm). The immunopositive reaction at
      the electron microscope was found to be largely confined to the dense-cored
      granules.

PMID- 7821781
TI  - Regional distribution and immunocytological localization of red pigment
      concentrating hormone in the crayfish eyestalk.
AB  - A polyclonal antibody was raised against synthetic tyrosinated crustacean red
      pigment concentrating hormone (RPCH-Tyr) with the sequence Tyr-Leu-Asn-Phe-Ser
      Pro-Gly-Trp-NH2 with a tryptophan amide at the carboxyl terminal end. Its
      specificity was tested in comparison with peptides of similar structure. It
      appears to recognize the three to five residues near the carboxyl terminal.
      Native RPCH in the crayfish eyestalk was determined by two methods: (a)
      immunoenzymatic assay (ELISA) using the aforementioned antibody; and (b) bioassay
      on segments of isolated crayfish tegumentary epithelium. The unitary content in
      whole eyestalks was 5.5 +/- 1.0 nmol for samples (n = 18) taken at night. The
      regional distribution of RPCH content in the eyestalk was determined. The
      greatest proportion (40%) was found in the sinus gland, and the lowest in the
      retina plus lamina ganglionaris (6%). The medulla interna, medulla externa, and
      medulla terminalis contained similar proportions (about 16% each). The highest
      specific content was in the sinus gland (65.0 vs 24.4 pmol/micrograms protein for
      the whole eyestalk). Immunopositive neurons were identified in the various
      regions of the eyestalk. In 22 preparations, an average of 7 cells were
      identified in the ventromedial rim of the medulla terminalis, sending axons to
      the sinus gland, after branching in the neuropil of the medulla terminalis.
      Dorsally, 2 cells were identified in the medulla interna and 4 large cells and 11
      small cells were located in the medulla externa in close proximity to the lamina
      ganglionaris: none of these cells appeared to project to the sinus gland. Profuse
      immunopositive fibers were found in the lamina ganglionaris projecting distally
      toward the base of the retina. Immunopositive axons were also found in the optic
      nerve.

PMID- 7821782
TI  - Identification of alpha-adrenergic receptors in catfish liver and their
      involvement in glucose release.
AB  - This study aimed to characterize alpha-adrenergic receptors in catfish
      hepatocytes in which catecholamine-induced calcium transients have been observed.
      alpha-Adrenergic binding sites were studied in purified liver membranes using the
      specific alpha 1-receptor antagonist [3H]prazosin. At 22 degrees C specific
      binding of [3H]prazosin is saturable, reversible, and linear as a function of
      tissue concentration; the association reaches a maximum at 15 min, and the half
      time for dissociation is about 4 min. Analysis of binding data suggests a single
      class of binding sites with a Kd of 1.6 nM and a Bmax of 182.1 fmol/mg protein.
      The relative potency of selective adrenoceptor ligands points to the presence in
      catfish liver of alpha-adrenergic receptors in addition to the beta-adrenergic
      receptor population previously characterized. Moreover, the binding data have
      been correlated to the glucose release from isolated hepatocytes suspended and
      perifused in a BioGel column, suggesting the involvement of alpha-adrenergic
      receptors in the glycogenolytic response to catecholamines in catfish
      hepatocytes.

PMID- 7821783
TI  - An enzyme immunoassay for salmon gonadotropin-releasing hormone and its
      application to the study of the effects of diet on brain and pituitary GnRH in
      the sea bass, Dicentrarchus labrax.
AB  - The effects of two different diets [diet 1 (D1), high protein-low carbohydrate;
      diet 2 (D2), low protein-high carbohydrate] on brain and pituitary gonadotropin
      releasing hormone (GnRH) contents, as well as circulating steroids and
      vitellogenin, were studied over the reproductive period of the sea bass. Salmon
      GnRH was measured using a newly developed competitive enzyme immunoassay with an
      enzymatic tracer made of sGnRH covalently coupled to acetylcholinesterase from
      the electric organ of the eel Electrophorus electricus. The pituitary GnRH
      content of animals of both sexes fed D1 was significantly reduced at the time of
      spawning compared with the pre- and postspawning stages, whereas fish fed D2 did
      not exhibit such changes. In the brain only minor differences in the GnRH content
      were observed between the two diets. It is concluded that GnRH release rather
      than synthesis is affected in fish fed a low protein-high carbohydrate regimen.
      Plasma sex steroids and vitellogenin were not greatly affected by the diet.

PMID- 7821784
TI  - Photoperiodic differences during development in the dwarf hamsters Phodopus
      sungorus and Phodopus campbelli.
AB  - The dwarf hamsters Phodopus sungorus and to a lesser extent Phodopus campbelli
      are widely used to study pineal physiology and seasonal reproduction because of
      their marked responses to photoperiod in adulthood. These species are frequently
      confused, partly because the common names "Siberian hamster" and "Djungarian
      hamster" are applied to both, often interchangeably. The current study examines
      whether the effects of photoperiod on reproductive maturation and prolactin
      secretion differ between these closely related species. Both male and female P.
      sungorus and P. campbelli were gestated and raised in long days (LD) of 16 hr
      light: 8 hr dark or in short days (SD) of 8 hr dark: 16 hr light. They were
      raised in pairs of the same sex after weaning at 21 days of age. Reproductive
      organ weights and serum prolactin concentrations were studied at 35 and 70 days
      of age. Whereas reproductive development proceeded rapidly in LD in both male and
      female P. sungorus, SD photoperiod completely inhibited growth of the gonads
      during this study. There were also marked differences in serum prolactin
      concentrations in both sexes of P. sungorus at all ages: levels were
      approximately 10-fold higher in LD than in SD. In P. sungorus of both sexes, SD
      also significantly decreased body weight relative to conspecifics raised in LD.
      In P. campbelli, reproductive maturation in LD occurred even more rapidly than in
      P. sungorus. Although significant effects of photoperiod were still apparent, the
      magnitude of its effect was less marked than in P. sungorus, and a substantial
      degree of reproductive development was observed in SD-reared males and
      females.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7821785
TI  - Effects of environmental salinity on pituitary growth hormone content and cell
      activity in the euryhaline tilapia, Oreochromis mossambicus.
AB  - Studies were undertaken to determine whether several indicators of growth hormone
      (GH) cell activity, namely GH content, fine structure, and volume of the GH
      region, differ in the pituitaries of freshwater (FW) and seawater (SW) tilapia,
      Oreochromis mossambicus. Tilapia raised from the stage of yolk-sac absorption for
      7 months in SW contain significantly more GH in their pituitaries than in those
      of fish reared in FW. Pituitary growth hormone content in tilapia raised in FW
      for 7 months and transferred to SW for 49 days is greater than that in sibling
      tilapia retained in FW. Conversely, GH content is significantly lower in the
      pituitaries of SW-reared tilapia transferred to FW for 49 days than that in the
      pituitaries from fish retained in SW. Likewise, the volume of the GH region and
      activity of the GH cells are enhanced in pituitaries from SW-reared tilapia over
      that seen in pituitaries from FW fish. Taken together, all data indicate
      heightened GH cell activity in SW-raised tilapia and suggest that GH may play a
      causal role in the greater growth rates observed in SW tilapia compared to FW
      fish and/or that GH may be involved in SW osmoregulation. The latter suggestion
      is supported, in part, by our observation that in vivo oGH treatment (2
      micrograms/g body wt) stimulated gill Na+,K(+)-ATPase activity.

PMID- 7821786
TI  - Anatomy of the stimulative sequences flanking the ARS consensus sequence of
      chromosome VI in Saccharomyces cerevisiae.
AB  - We have analyzed the relationship between autonomously replicating sequence (ARS)
      structure and function for three ARS (ARS605, ARS607 and ARS609) from chromosome
      VI of Saccharomyces cerevisiae by systematic XhoI-linker mutation in the ARS
      consensus sequence (ACS) and flanking sequences. All mutations that encroached
      upon the ACS destroyed ARS activity. DNA sequences stimulative for ARS function
      were identified on either side of the ACS of ARS605 and only on the 3'-side of
      the ACS of ARS607. In ARS609, however, no such stimulative sequences were
      observed. Base substitutions complementary to the wild-type sequence of those
      stimulative regions, in ARS605 and ARS607, that did not change the delta G of
      unwinding nor affected ARS activity suggests that these regions have, at least, a
      function as DNA-unwinding elements (DUE). ARS605, ARS607 and ARS609 DNA are of
      low delta G value and showed hypersensitivity to single-strand-specific nuclease
      when inserted in negatively supercoiled plasmid. Linker mutations inhibitory for
      ARS activity (5L11 and 7L14) also caused significant changes in local nucleotide
      (nt) sensitivity within the ACS and its adjoining regions. Complementary base
      substitutions, however, did not affect these changes in local nt sensitivity.
      These results imply that the stimulative regions flanking the ACS are necessary
      to produce an optimum conformation around the ACS which may be important for full
      ARS activity.

PMID- 7821787
TI  - Cloning, expression and characterization of thymidylate synthase from
      Cryptococcus neoformans.
AB  - The thymidylate synthase (TS)-encoding gene from Cryptococcus neoformans (Cn) has
      been isolated from cDNA and genomic libraries. The 1127-bp gene contains three
      introns and a 951-bp open reading frame encoding a 35,844-Da protein. The cDNA
      clones lack 324 bp of the 5' coding region of the gene. The complete coding
      sequence was assembled as an expression cassette in pUC19 using parts of the
      coding sequence from the cDNA and genomic DNA and completing the sequence using
      synthetic DNA. Production of active TS from Cn (CnTS) was first demonstrated by
      complementation of a thymine(Thy)-requiring Escherichia coli strain. The
      expression cassette was subsequently subcloned into the T7 polymerase vector
      pET15-b. In this construct, CnTS is produced as approximately 10% of the total
      soluble protein in E. coli. Homogeneous enzyme was obtained at a 36% yield after
      consecutive chromatography on DEAE-cellulose, Q-Sepharose, phenyl-Sepharose and
      Affi-Gel Blue. Steady-state kinetic analysis showed that the Km values for dUMP
      and CH2H4.folate were 2.7 +/- 0.5 microM and 38.2 +/- 2.5 microM, respectively,
      and the kcat was 5.1 s-1. The enzyme was stable upon storage at -80 degrees C in
      Tris.HCl pH 7.4 and thiol.

PMID- 7821788
TI  - Structure of the gene encoding pig phosphoglucose isomerase.
AB  - Genomic clones encoding pig phosphoglucose isomerase (PGI) have been isolated and
      partially sequenced. The gene (Pgi) contains 18 exons, 17 introns and spans about
      32 kb. This structure is partially conserved between plant and animal. A major
      transcription start point (tsp) has been identified 74 nucleotides (nt) upstream
      from the AUG. The nt sequence around the tsp is very G+C rich; a 5'-ATAAA
      sequence, as well as four putative Sp1-binding sites, are present. In the 3'
      flanking region, an AATAAA signal has been identified. Extending from the 5'
      flanking region to the first intron, a 0.6-kb CpG island has been identified. The
      Pgi structural gene contains several DNA repetitive elements in its non-coding
      regions.

PMID- 7821789
TI  - Construction of a human full-length cDNA bank.
AB  - We aimed to construct a full-length cDNA bank from an entire set of human genes
      and to analyze the function of a protein encoded by each cDNA. To achieve this
      purpose, a multifunctional phagemid shuttle vector, pKA1, was constructed for
      preparing a high-quality cDNA library composed of full-length cDNA clones which
      can be sequenced and expressed in vitro and in mammalian cells without subcloning
      the cDNA fragment into other vectors. Using this as a vector primer, we have
      prepared a prototype of the bank composed of full-length cDNAs encoding 236 human
      proteins whose amino acid sequences are identical or similar to known proteins.
      Most cDNAs contain a putative cap site sequence, some of which show a pyrimidine
      rich conserved sequence exhibiting polymorphism. It was confirmed that the vector
      permits efficient in vitro translation, expression in mammalian cells and the
      preparation of nested deletion mutants.

PMID- 7821790
TI  - Characterization of hUCRBP (YY1, NF-E1, delta): a transcription factor that binds
      the regulatory regions of many viral and cellular genes.
AB  - The UCRBP (YY1, delta, NF-E1) protein has been isolated for its ability to bind
      to the UCR (upstream conserved region) site present in the conserved murine
      leukemia virus long terminal repeat. UCRBP carries a highly charged N-terminal
      domain and four C2-H2-type zinc fingers at its C-terminal end. The present study
      reveals the following results: (i) The UCR site is present in the upstream and/or
      regulatory regions of numerous mammalian cellular and viral genes to which both
      recombinant and cellular UCRBP bind. UCR sites are also found in the regulatory
      regions of repetitive sequences including human LINE-1 elements and mouse
      intracisternal-A particle sequences. (ii) By immunological and UV cross-linking
      experiments, we found that two proteins, of approx. 68 kDa and an antigenically
      related protein of approx. 40 kDa, account for much of the UCR-binding activity
      in T-lymphocytes. (iii) There is evidence that UCRBP acts as a phosphoprotein.
      Eight consensus phosphorylation sites are found in the deduced amino-acid
      sequence of human UCRBP. The cellular UCR-binding activity was abolished by
      phosphatase treatment, and there is an incremental increase in apparent molecular
      mass between the cytoplasmic and nuclear forms of the protein, suggesting
      phosphorylation. (iv) Although UCRBP has been previously shown to act as a
      transcriptional repressor, we show here that UCRBP can also act as a positive
      transactivator of a reporter driven by UCR elements when used in co-transfection
      assays. This transactivation occurred in a dose-restricted manner and was absent
      at high concentrations of a UCRBP expression plasmid, indicating a complex mode
      of function.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7821791
TI  - A copy-number-controlled expression vector for the fission yeast
      Schizosaccharomyces pombe.
AB  - A novel expression vector for the fission yeast Schizosaccharomyces pombe carries
      the neomycin-resistance-encoding gene regulated by the SV40 early promoter, and
      its copy number is controlled by the level of Geneticin (G418). Foreign gene
      expression is driven by the human cytomegalovirus (hCMV) promoter which is
      transcriptionally active in S. pombe. Moreover, the vector expresses foreign
      genes at high levels, due to the 5'-untranslated region (5'-UTR) containing an A
      + T-rich sequence of about 50 nucleotides located between the TATA box of the
      hCMV promoter and the start codon. Recombinant human lipocortin I was produced at
      levels of up to 50% of the total soluble protein in the presence of 100-200
      micrograms/ml of G418 in the media. Southern and Northern blotting showed that
      this high level of expression was due to an increase in copy number induced by
      G418, the high transcriptional activity of the hCMV promoter and the high
      translational efficiency of the 5'-UTR. We modified the vector into an 'ATG
      vector', named pTL2M, that maintains the 5'-UTR optimized for gene expression and
      into which any foreign gene, whose exact sequence is known, can be easily
      inserted.

PMID- 7821792
TI  - Schizosaccharomyces malidevorans and Sz. octosporus homologues of Sz. pombe rad9,
      a gene that mediates radioresistance and cell-cycle progression.
AB  - The rad9 gene of Schizosaccharomyces pombe is involved in promoting resistance to
      ionizing radiation and UV light, as well as regulating cell cycle progression
      after irradiation. We have isolated functional rad9 cognates from two other
      fission yeasts, Sz. malidevorans and Sz. octosporus, that can restore
      radioresistance and the radiation-induced G2 delay response to Sz. pombe
      rad9::ura4 cells. The Sz. pombe and Sz. malidevorans genes are identical at the
      nucleotide sequence level, which reflects their close evolutionary relationship.
      Each bears three introns and codes for a 47 464-Da protein that contain 426 amino
      acids (aa). In contrast, Sz. octosporus rad9 contains five introns and codes for
      a 48 210-Da protein that is 432-aa long. The Sz. pombe rad9 product is only 65%
      identical and 80% similar to the corresponding Sz. octosporus gene product. All
      of the strains synthesize a rad9 RNA of approx. 1.6 kb. The presence of a rad9
      like gene in these yeasts suggests that the cellular process(es) mediated by
      rad9, and used by these organisms to increase survival and transiently delay
      cycling in G2 after irradiation, are conserved. The isolation, analyses and
      comparison of rad9 genes from different organisms should aid in elucidating the
      specific biological role of the corresponding protein and especially help
      pinpoint regions important for function.

PMID- 7821793
TI  - Isolation and characterization of an Aspergillus nidulans gene encoding an
      alkaline protease.
AB  - We have cloned an Aspergillus nidulans gene (prtA) encoding an alkaline protease
      (Alp) by probing an A. nidulans library with a fragment amplified from an
      Aspergillus oryzae Alp-encoding gene. The nucleotide (nt) sequence of prtA was
      determined. The structure of prtA is similar to that of the A. oryzae Alp
      encoding gene. The prtA gene is composed of four exons which are separated by
      three introns of 59, 57 and 54 nt. The deduced amino acid sequence of the prtA
      product shows a high degree of similarity to proteases from A. oryzae, A.
      fumigatus and A. flavus. Southern blot analysis suggests that only one copy of
      this gene is found in the genome of A. nidulans. The extracellular proteases of
      A. nidulans are regulated by nitrogen, carbon and sulfur metabolite repression.
      The prtA RNA levels were analysed under different nutrient conditions. No prtA
      transcript was detected in mycelium grown in medium containing glucose, NH4+ and
      sulfate. However, prtA transcript levels were high in mycelia transferred to
      medium lacking a nitrogen, carbon or sulfur source.

PMID- 7821794
TI  - An autonomously propagating luciferase-encoding vector for Dictyostelium
      discoideum.
AB  - We have constructed a luc reporter vector for Dictyostelium discoideum using a
      626-bp fragment from the nuclear-associated plasmid Ddp2. The ori from Ddp2 is
      localized within this fragment and was used to provide an autonomous replication
      sequence for the reporter vector. This reporter vector was stably retained in D.
      discoideum AX3K cells without alteration. The vector molecule was also found to
      exist in relatively low copy number compared to other Dictyostelium vectors in
      the transformed cells. We demonstrated the utility of this vector as a reporter
      vector with glycogen synthase promoter/luc fusions of varying sizes.

PMID- 7821795
TI  - The cryptomonad histone H4-encoding gene: structure and chromosomal localization.
AB  - Cryptomonads are unicellular flagellates whose plastids are surrounded by four
      membranes. A periplastidal compartment, containing eukaryote-type ribosomes,
      starch grains and a so-called nucleomorph, is located between the inner and outer
      membrane pairs. The nucleomorph has been shown to be the vestigial nucleus of a
      eukaryotic endosymbiont. In order to obtain more information about the chromatin
      structure of the nucleomorph and the host nuclear chromosomes, we studied the
      distribution of the histone, H4. H4 was not detectable in the nucleomorph by
      immunolocalization, thus supporting earlier findings by Gibbs [In: Wiesner et al.
      (Eds.), Experimental Phycology 1, 1990, pp. 145-157]. Likewise, no H4 DNA was
      demonstrable in the nucleomorph by Southern hybridization. Sequence analysis, and
      Southern and Northern blot data of a cryptomonad gene, H4, indicate an
      intermediate position for these genes between animals and plants.

PMID- 7821796
TI  - Mutational analysis of the proteolytic cleavage site of glycoprotein B (gB) of
      Marek's disease virus.
AB  - The Marek's disease virus (MDV) glycoprotein B (gB) precursor, gp100, is
      proteolytically cleaved into two disulfide-linked subunits, gp60 and gp49. In the
      gB homologs of most other herpesviruses, a tetrapeptide, Arg-Xaa-Arg-Arg, is
      immediately upstream from the predicted cleavage site. We have investigated the
      specificity of the proteolytic cleavage in gp100 by introducing mutations within
      its predicted cleavage site (Arg-Leu-Arg-Arg) and expressed these mutants in
      recombinant fowlpox virus (FPV). The results show that all three Arg residues at
      the predicted cleavage site play an important role in the specific proteolytic
      cleavage of gp100. Furthermore, we demonstrated that the cleavage of gp100 is not
      necessary for transport of gB to the cell surface.

PMID- 7821797
TI  - Biological activity and intracellular location of the Tat protein of equine
      infectious anemia virus.
AB  - The Tat protein of equine infectious anemia virus (EIAV) was synthesized in
      Escherichia coli using the inducible expression plasmid, pET16b, which contains a
      His.Tag leader, thus allowing for rapid and efficient enrichment of the histidine
      tagged protein by metal affinity chromatography. Yields of up to 20 mg of Tat
      were obtained from 10(11) bacterial cells. The recombinant Tat protein was shown
      to potently trans-activate the EIAV long terminal repeat (LTR) following its
      introduction into canine cells by 'scrape loading'. The EIAV Tat protein was
      found to localize predominantly within the cytoplasm, in contrast to HIV-1 Tat.
      The availability of large amounts of purified functional EIAV Tat protein should
      greatly facilitate detailed structure-function analyses.

PMID- 7821798
TI  - Identification of the promoter region of chicken anemia virus (CAV) containing a
      novel enhancer-like element.
AB  - The single promoter region in the cloned genome [Noteborn et al., J. Virol. 65
      (1991) 3131-3139] of chicken anemia virus (CAV) in chicken T-cells was analysed
      via CAT assays. A unique region containing four or five near-perfect direct
      repeats (DR) of 21 bp with one 12-bp insert was proven to be the main
      transcription-activation element, with enhancer-like characteristics. PCR studies
      revealed that CAV isolates from across the world all contained this promoter
      sequence. Electrophoretic mobility-shift assays (EMSA) showed that individual DR
      units, as well as the 12-bp insert, can bind to nuclear factors of chicken T
      cells. Competition assays revealed that the DR units bound to factors other than
      the 12-bp insert. A synthetic oligodeoxyribonucleotide containing an SP1-box (5'
      GGGCGG) could compete with factors binding to the 12-bp insert. Purified human
      SP1 was shown to have very strong affinity for the 12-bp insert.

PMID- 7821799
TI  - Expression of the tyrosinase-encoding gene in a colorless melanophore mutant of
      the medaka fish, Oryzias latipes.
AB  - In the medaka fish Oryzias latipes many mutants for body colors have been
      isolated. Among them, a colorless melanophore mutant b, carrying b alleles
      homozygously, has pigmented black eyes but orange-colored skin with amelanotic
      melanophores, suggesting the presence of a tissue-specific mechanism of melanin
      formation. To cast light on the molecular basis of the mechanism, we have cloned
      cDNAs for tyrosinase (Tyr), a key enzyme in melanin biosynthesis, from the wild
      type (wt) fish. DNA sequence analysis revealed that all clones encode a protein
      of 540 amino acids, having five potential glycosylation sites and two copper
      binding sites that are characteristic features of Tyr. Genomic DNA blot analysis
      disclosed that the Tyr gene is present as a single copy in the fish genome. Using
      a cDNA clone as a probe, RNA blot analysis was carried out. In the wt, the 2.2-kb
      Tyr mRNA was expressed in eyes and skin but not in liver, corresponding to tissue
      specific melanin formation. In the b mutant, contrary to expectation, the mRNA
      was detected not only in eyes but also in amelanotic skin. Therefore,
      pigmentation of the skin controlled by b is not directly related to expression of
      the Tyr gene.

PMID- 7821800
TI  - Production of a functional full-length Xenopus laevis c-Myc protein in insect
      cells.
AB  - C-Myc is a nuclear phosphoprotein whose normal cellular function has not yet been
      clearly defined. Studies with this protein have always been constrained by the
      difficulty of obtaining full-length c-Myc in an active form, whatever the
      expression system used. We report here experimental conditions optimized to
      increase the solubility and the purification of c-Myc in a baculovirus expression
      system. Such conditions allow the production of both soluble and active full
      length c-Myc. Interestingly, soluble c-Myc is found associated with a 500-kDa
      high-molecular-mass complex comparable to that found in human and Xenopus laevis
      embryos, and which may be required for its function in vivo.

PMID- 7821801
TI  - Identification and characterization of a cDNA encoding ribosomal protein S12 from
      Xenopus laevis.
AB  - The complete nucleotide (nt) sequence of the cDNA clone XL-S12, encoding a
      Xenopus laevis (Xl) homologue of the mammalian ribosomal protein S12, has been
      determined. The sequence predicts a Xl S12 protein of 132 amino acids (aa) with a
      molecular mass of 14.7 kDa. Xl S12 shares 95 and 97% aa sequence identity with
      the human and murine S12 proteins, respectively. Analysis of nt substitution
      patterns and rates indicates that S12 is a very highly constrained protein,
      evolving at an estimated rate of only 0.03 x 10(-9) non-synonymous (protein
      altering) substitutions per site per year.

PMID- 7821802
TI  - Characterization of the 5' region of the Atlantic salmon (Salmo salar)
      transferrin-encoding gene.
AB  - A genomic fragment encompassing the first two exons and 1.3-kb 5'-flanking
      sequence of the Atlantic salmon transferrin (Tf)-encoding gene (sTf) has been
      isolated and characterized. The transcription start point of sTf was mapped to 48
      nucleotides upstream from the translation start codon. In the proximal promoter
      region (-118 to +1), sTf displays sequence similarity to the chicken, mouse and
      human Tf, and contains a TATA-box, CCAAT-box and CAAAC motif conserved during
      evolution. Putative binding sites for the transcription factors AP-2, AP-3, Sp1,
      CF1, NF-IL6, HNF-5, GCF and GATA-1 were identified in the sTf 5'-flanking
      sequence. An element with dyad symmetry is located between -219 and -201, and an
      alternating purine-pyrimidine (APP) sequence (a 24-bp imperfect CA repeat) is
      located at -187 to -164. A minisatellite consisting of 25 tanden repeats of a 37
      bp motif occupies the region between -1338 and -417. The Atlantic salmon has two
      Tf genes. Comparison of the 5'-end sequences (nt -383 to +80) of the two sTf
      revealed only minor differences, except that the length of a CA repeat differs by
      12 bp.

PMID- 7821803
TI  - Cloning of cDNAs coding for the G alpha i1 and G alpha i2 G-proteins from chick
      brain.
AB  - We have cloned and characterized several cDNAs coding for G-protein inhibitory
      alpha subunits (G alpha i) from a chick brain cDNA library. Based on homology to
      G alpha subunits from other eukaryotes, these clones were designated chick G
      alpha i1 and G alpha i2. On the deduced amino-acid level, G alpha i1 and G alpha
      i2 were found to be 98 and 95% identical to rat G alpha i1 and G alpha i2,
      respectively. Using RNase protection analysis, the G alpha i1 and G alpha i2
      mRNAs were found to be expressed in chick atria, ventricle, lung, liver, brain
      and kidney.

PMID- 7821804
TI  - Sequence and expression of murine cDNAs encoding Xlr3a and Xlr3b, defining a new
      X-linked lymphocyte-regulated Xlr gene subfamily.
AB  - Using a subtractive cDNA approach we have identified two nearly identical genes,
      Xlr3a and Xlr3b (X-linked lymphocyte regulated), expressed at a consistently high
      level in 14 out of 14 murine plasmacytoma cell lines, at a high level in 1 out of
      8 B-lymphoma cell lines, and at a very low level in 2 out of the 8 B-lymphoma
      cell lines. The messages are not detected in 10 pre-B-lymphoma cell lines. These
      genes express 2.0-kb mRNAs that encode 226-amino-acid proteins that are extremely
      basic, with an estimated pI of 8.1 and 9.0, respectively. By sequence comparison
      they are homologous to Xlr1, an acidic nuclear protein that is produced in
      lymphoid cell lines corresponding to the late stages of lymphocyte
      differentiation. Xlr2 is a highly homologous gene that is expressed in
      differentiating male germ cells. Xlr3a and Xlr3b are members of a new subfamily
      in the Xlr multigene family. Like Xlr1, they are up-regulated during B-cell
      terminal differentiation in normal and neoplastic B-cells, and cross-hybridize
      with a message in testis RNA. Also, like Xlr1, they do not cross-hybridize with
      human genomic DNA.

PMID- 7821805
TI  - Cloning of the Dck gene encoding rat deoxycytidine kinase.
AB  - In order to study the mutational inactivation of deoxycytidine kinase (Dck) in a
      rat model for acute myeloid leukemia we have cloned the complete coding region of
      the rat Dck gene. Using primers chosen from the human Dck cDNA sequence, we
      obtained a rat-specific probe via PCR and used it to isolate two clones from a
      rat lymphocyte cDNA library. The ORF showed 89.7 and 92.2% nucleotide identity
      with the human and mouse Dck, respectively, and encodes a 260-amino-acid protein,
      that is 91.9 and 94.6% homologous to human and mouse Dck, respectively. Northern
      blot analysis of rat tissues revealed high expression of a 4.1-kb Dck transcript
      in the thymus, whereas spleen, liver and lung samples showed weak expression of
      the gene. This tissue-specific expression pattern was confirmed by cDNA-PCR
      analysis.

PMID- 7821806
TI  - Cloning and sequencing of a full-length rat sucrase-isomaltase-encoding cDNA.
AB  - Sucrase-isomaltase (SI) has been widely used as a marker enzyme to study cellular
      differentiation in the small intestine. We isolated a 6.1-kb SI cDNA clone
      (GC1.4) from a size-fractionated cDNA library from rat intestine. Sequencing of
      this cDNA clone showed 6066 nucleotides (nt) with an open reading frame (ORF) of
      1841 amino acids (aa). The nt sequence correctly predicts several known aa
      stretches in the protein. The deduced as sequence showed 78 and 75% overall
      identity with the rabbit and human SI, respectively. At the active sites of both
      S and I, the rat nt sequence encodes stretches of 14 and 16 aa, respectively,
      which show 100% identity to rabbit and human SI. In the region immediately beyond
      the transmembrane domain, the rat sequence encodes an extra 10 aa, as compared to
      rabbit and human. This 10-aa insertion consists almost entirely of Pro, Ser and
      Thr, and may be responsible for additional O-glycosylations of rat SI. The cDNA
      contains a 3'-UTR (untranslated region) of 499 nt with polyadenylation signal
      sequence and a poly(A) tract. The ATG start codon was found 41 nt downstream from
      the 5' end of the cDNA. Primer extension experiments showed the cap site to be 61
      nt upstream from the start codon. The results indicate that our cDNA clone lacks
      only 20 nt in the 5'-UTR. Given that this cDNA encodes the entire coding region
      of SI, it should be useful in elucidating the regulatory mechanisms of SI
      biosynthesis, localization and targeting during rat intestinal development and
      differentiation.

PMID- 7821807
TI  - Isolation of a potentially functional HPRT processed pseudogene from the hill
      kangaroo Macropus robustus.
AB  - A highly conserved hypoxanthine phosphoribosyltransferase processed pseudogene
      (KPH) has been isolated from a female kangaroo (Macropus robustus) lambda EMBL3
      genomic library. The pseudogene contains only transcribed material with all of
      the introns precisely removed and has possible direct repeats at either end of
      the message. It has a 654-nucleotide open reading frame (ORF) from the Met start
      codon to the stop codon that contains no additions, deletions or premature stops
      relative to expressed HPRT genes and, therefore, the possibility exists that it
      is expressed in vivo. Possible CAAT and GC boxes are present in the region 5' to
      the ORF and a polyadenylation signal is present in the region 3' to the ORF. If
      not expressed, the age of the pseudogene is estimated to be 10.7 million years.
      We propose that integration into the genome occurred specifically in a
      homocopolymeric region within a highly repeated region unique to the kangaroo
      genome.

PMID- 7821808
TI  - Sequencing of the ovine interleukin-8-encoding cDNA using the polymerase chain
      reaction.
AB  - The nucleotide (nt) sequence encoding the ovine homologue of interleukin-8 (IL-8)
      was determined. The mRNA is 1494-nt long with an ORF of 101 codons. The long 3'
      non-coding element contains several ATTTA repeats implicated in the swift
      turnover of other chemokine mRNAs. The encoded protein of 11 kDa before
      processing, and 9 kDa as mature protein, contains the Cys-Xaa-Cys motif common to
      alpha-chemokines, and has conserved amino acids (aa) at positions identified as
      receptor contact sites for IL-8. Identities with other published IL-8 aa
      sequences are: dog, 91%; pig, 87%; rabbit, 84%; human, 78%; guinea pig, 69%. A
      49% aa identity is also found with a chicken embryo fibroblast protein.

PMID- 7821809
TI  - Sequence and chromosomal localisation of the gene encoding ovine latent
      transforming growth factor-beta 1.
AB  - Transforming growth factor-beta 1 (TGF-beta 1) plays important roles in
      pathologic processes. To further investigate the actions of this cytokine in
      sheep, the entire 1170-bp ovine TGF-beta 1 pro-protein-encoding sequence has been
      determined by the cloning and sequencing of specific polymerase-chain-reaction
      amplification products of TGF-beta 1 cDNA sequences. In addition, these sequences
      have been used to estimate the length of the TGF-beta 1 mRNA as 1.5-1.7 kb by
      Northern blot hybridization and determine that the ovine TGF-beta 1 gene occupies
      a single locus in the sheep genome by chromosomal in situ hybridization.

PMID- 7821810
TI  - Cloning and identification of the pig ribosomal gene promoter.
AB  - Pig ribosomal RNA-encoding gene (rDNA) clones were obtained by screening a pig
      genomic DNA library. A 742-bp segment containing the promoter was sequenced.
      Using total pig RNA, the tsp (transcription start point) was defined by primer
      extension. A promoter-like region was found immediately upstream from the active
      promoter. Promoter function was studied by transfection of pig tissue culture
      cells and assayed by a highly sensitive RT-PCR method. Alignment of five
      mammalian rDNA promoter sequences, human, mouse, rat, rabbit and pig, showed five
      conserved subregions which may be important in transcriptional regulation. An
      unusual feature of the pig rDNA promoter is that instead of a G at -16, which is
      conserved in eukaryotes, there is a C.

PMID- 7821811
TI  - Cloning, sequencing and partial functional characterization of the 5' region of
      the human p75 tumor necrosis factor receptor-encoding gene (TNF-R).
AB  - A 1887-bp region at the 5' flank of the human p75 tumor necrosis factor receptor
      (p75 TNF-R)-encoding gene was found to be active in driving expression of the luc
      (luciferase-encoding) reporter gene, suggesting that it contains the promoter for
      the receptor. Rather unexpectedly, a 1827-bp region at the 3' end of the first
      intron of the p75 TNF-R gene also displayed promoter activity. This activity may
      be artefactual, reflecting only the presence of an enhancer in this region; yet
      it also raises the possibility that p75 TNF-R is controlled by more than one
      promoter and that it encodes various forms of the receptor, or even other
      proteins. We present here the nucleotide sequences of the 5' flanking and intron
      regions. Possible implications for the transcriptional regulation of the p75 TNF
      R gene are discussed.

PMID- 7821812
TI  - The effect of intron sequences on expression levels of Ig cDNAs.
AB  - Several cDNA expression vectors were constructed and tested by stable
      transfection into a murine lymphoid cell line in order to compare secretion rates
      of a human immunoglobulin (Ig) light chain (LC). When the cDNA was under
      transcriptional control of the SV40 promoter and enhancer and preceded by the
      SV40 19S late mRNA intron, a weak LC production was detected. Secretion rate was
      not improved by replacing the SV40 promoter and enhancer by a combination of a
      murine Ig heavy chain (HC) gene promoter and enhancer even with insertion of
      additional Ig enhancers. In contrast, replacement of the 19S intron by a large
      intron derived from a human Ig HC gene and containing the intronic enhancer
      dramatically increased the secretion rate. High-level production was also
      obtained with the same enhancer-containing intron placed downstream from the LC
      cDNA. Stable transfectants were obtained that secreted the human LC in amounts
      comparable to those obtained with Ig genes. Our results suggest that the SV40 19S
      late mRNA intron used in several expression vectors is not appropriate when the
      purpose is to produce large amounts of antibody molecules. By providing
      transcriptional, splicing and polyadenylation signals, the presently described
      vectors will be useful for easy cloning and high-level expression in lymphoid
      cells of cDNAs or PCR products encoding antibody molecules.

PMID- 7821813
TI  - Sequence of the 5'-flanking region of the gene encoding human muscle glycogen
      synthase.
AB  - The 5'-flanking region of the gene encoding human muscle glycogen synthase was
      isolated from a human placental genomic library and sequenced. The sequence is
      TATA-less and G+C-rich, and putative transcription-controlling sequences were
      identified. Furthermore, a simple (dC-dA)n sequence repeat was identified about 4
      kb upstream from the start codon. This sequence was highly polymorphic and five
      alleles were typed in the Japanese population using the polymerase chain
      reaction.

PMID- 7821814
TI  - Cloning and characterization of the human gene encoding aspartyl beta
      hydroxylase.
AB  - Sequence information for aspartyl beta-hydroxylase (AspH), which specifically
      hydroxylates one Asp or Asn residue in certain epidermal growth factor (EGF)-like
      domains of a number of proteins, is so far only described for bovine species. We
      have isolated a 4.3-kb cDNA encoding the human AspH (hAspH) by immunoscreening of
      a human osteosarcoma (MG63) cDNA library in lambda ZAP with an antiserum raised
      against membrane fractions of these cells. Northern blot analyses revealed two
      transcripts with lengths of 2.6 and 4.3 kb. The deduced amino acid (aa) sequence
      of this cDNA encodes a protein of 757 aa (85 kDa). Comparison with the deduced
      bovine AspH (bAspH) aa sequence showed striking differences in the N-terminal
      portion of this protein. In vitro transcription and translation in the presence
      of canine pancreas microsomes yielded a 56-kDa protein. Western blot analyses of
      membrane fractions from MG63 cells with AspH-specific antibodies revealed a
      protein of the same M(r). These results suggest a posttranslational cleavage of
      the catalytic C terminus in the lumen of the endoplasmic reticulum.

PMID- 7821815
TI  - The Saccharomyces cerevisiae homologue of ribosomal protein S26.
AB  - The nucleotide sequence of RPS26, the gene encoding a homologue of ribosomal
      protein small subunit S26 in Saccharomyces cerevisiae, was determined. The
      deduced amino-acid sequence showed significant identity with its counterparts
      from Neurospora crassa, human, rat and Arabidopsis thaliana. Disruption of RPS26
      resulted in the formation of micro-colonies, suggesting that it is important for
      the normal cell growth of S. cerevisiae.

PMID- 7821816
TI  - Corrected sequence of the yeast neutral trehalase-encoding gene (NTH1):
      biological implications.
AB  - We have identified a sequencing error in the neutral trehalase-encoding gene NTH1
      [Kopp et al., J. Biol. Chem. 268 (1993) 4766-4774]. This error extends the
      deduced amino acid (aa) sequence at the N terminus by 58 aa. The biological
      implications of this include the presence of an additional phosphorylation site,
      which is believed to regulate trehalose hydrolysis.

PMID- 7821818
TI  - Cloning and analysis of the gene encoding lectin from the acorn barnacle
      Megabalanus rosa.
AB  - In the acorn barnacle Megabalanus rosa, two types of galactose-binding C-type
      lectins (BRA-2 and BRA-3) have been identified. Here, we report the isolation and
      characterization of BRA-2 cDNA and genomic clones. In contrast to the BRA-3 gene,
      which consists of four exons, BRA-2 is encoded by a single exon, implying
      differences in the physiological roles of the two lectins.

PMID- 7821817
TI  - An improved cosmid vector for the cloning of equine herpesvirus DNA.
AB  - We have modified the commercial cosmid vector, triple helix vector (THV), such
      that I-Sce-I restriction endonuclease sites flank the cloning site. I-Sce-I is a
      rare-cutting endonuclease which recognizes an 18-bp sequence. It does not
      restrict the genome of either of the equine herpesvirus 1 or 4 (EHV-1 and EHV-4)
      strains we have cosmid cloned. Thus, cosmid-cloned EHV fragments can be excised
      intact from the vector by I-Sce-I digestion, facilitating production of large
      overlapping EHV fragments for use in transfections to produce recombinant virus.

PMID- 7821819
TI  - A rapid procedure for the humanization of monoclonal antibodies.
AB  - An efficient and rapid procedure for the humanization of murine monoclonal
      antibodies (MumAb) is described. It consists of site-directed mutagenesis (SDM)
      to transfer the murine complementarity-determining regions (MuCDR) onto human
      framework regions (HuFR), followed by polymerase chain reaction (PCR) of the SDM
      product. Using SDM/PCR, rapid and correct humanization of MumAb heavy chains is
      clearly demonstrated. Compared to current protocols this method considerably
      reduces the time and labour required to generate humanized mAb.

PMID- 7821820
TI  - A eukaryotic expression vector for the study of nuclear localization signals.
AB  - We describe a new vector designed to produce beta-galactosidase fusion proteins
      which can be used to assess subcellular localization of target peptide fragments
      or proteins in eukaryotic cells. The vector was constructed in such a way as to
      produce the peptide of interest in fusion via a short linker of proline residues
      to the N terminus of the reporter protein. Efficiency of the transport machinery
      is optimized using this particular protein fusion construction. This vector has
      potential uses for readily testing putative nuclear localization sequences and
      identifying their crucial amino-acid residues.

PMID- 7821821
TI  - A human cDNA encoding the small subunit of RNA polymerase II transcription factor
      SIII.
AB  - A full-length cDNA encoding a human homolog of the 15-kDa subunit (p15) of RNA
      polymerase II elongation factor SIII was isolated and sequenced. Comparison of
      the open reading frames of the human p15 cDNA and the previously characterized
      rat p15 cDNA [Garrett et al., Proc. Natl. Acad. Sci. USA 91 (1994) 5237-5241]
      indicates that they encode identical proteins and are 93% conserved in nucleotide
      sequence.

PMID- 7821822
TI  - Lissencephaly-1 is one of the most conserved proteins between mouse and human: a
      single amino-acid difference in 410 residues.
AB  - The nucleotide (nt) sequence of the LIS-1 cDNA encoding the murine lissencephaly
      1 (LIS-1) protein has been determined. The deduced protein shows a very high
      degree (99.8%) of homology with human LIS-1, having a single conservative amino
      acid (aa) change out of 410 aa and is identical to a subunit of bovine platelet
      activating factor (PAF) acetylhydrolase.

PMID- 7821823
TI  - The sequence of a human mitochondrial glycerol-3-phosphate dehydrogenase-encoding
      cDNA.
AB  - A 2618-bp cDNA that encodes the human mitochondrial glycerol-3-phosphate
      dehydrogenase has been isolated from a HeLa cell cDNA library and the nucleotide
      sequence determined. An open reading frame encodes a protein of 727 amino acids
      that is 96% similar to the rat protein and, like the rat protein, contains sites
      homologous to the Ca(2+)-binding sites of calmodulin, as well as FAD- and
      putative glycerol-phosphate-binding sites.

PMID- 7821824
TI  - Putting a face on Alzheimer's disease.

PMID- 7821825
TI  - Impotence: should primary care physicians give penile injections?

PMID- 7821826
TI  - When your patient needs surgery: weighing risks versus benefits.
AB  - The likelihood of being a candidate for elective or emergency surgery increases
      with age. The higher rates of perioperative morbidity and mortality seen in older
      patients result in part from co-existing medical illnesses. Age alone should not
      be a contraindication for surgery, however, and the long-term benefits of
      procedures such as coronary artery bypass grafting appear similar for young and
      old. Emergency operations account for 39 to 75% of all surgery after age 70 and
      carry a 20-fold increase in mortality compared with elective procedures.
      Appropriate surgical interventions, therefore, should not be deferred simply
      because the patient is elderly. Age-associated changes in body composition and
      organ physiology contribute to the risk of perioperative complications.

PMID- 7821827
TI  - Pressure ulcers: a strategic plan to prevent and heal them.
AB  - Pressure ulcers are common in frail, disabled, or acutely ill older patients in
      the home, hospital, or nursing home. Prevention is the most important aspect of
      pressure ulcer care, and physician and nurse share in this responsibility. A
      nosocomial pressure ulcer adds significantly to mortality, morbidity, and
      hospital length-of-stay. Risk factor assessment scales can help identify patients
      who need prevention efforts, such as pressure relief, incontinence care, and
      nutritional supplements. When an ulcer does occur, careful documentation is
      required, including staging, size and depth description, and review of the
      interdisciplinary care plan. Knowledge of wound biology and cost-effectiveness
      should guide the choice of wound healing products.

PMID- 7821828
TI  - How to manage depression and psychosis in Alzheimer's disease.
AB  - Depression and psychosis each occur in about 30 to 50% of patients with
      Alzheimer's disease (AD). Depressive syndromes range from grieving and mild
      depressive symptoms to major depression. Depression can also mimic the signs and
      symptoms of AD, a condition known as dementia syndrome of depression. Psychotic
      syndromes include paranoid delusions, misidentification syndrome, and
      hallucinations. The diagnosis of both depression and psychosis is based on a
      careful history and a mental status examination. Treatment includes psychosocial
      intervention and, when symptoms are severe, drug therapy. The newer
      antidepressants are recommended for depressive syndromes, whereas psychosis is
      treated with high-potency neuroleptics.

PMID- 7821829
TI  - [Severe pre-eclampsia and HELLP syndrome].
AB  - This is a review of 15 cases of severe pre-eclampsia with HELLP syndrome. The
      patients presented with severe arterial hypertension, the main symptoms were
      epigastric and right hypochondrial pain that were present in 66.6% of the
      patients, nausea and vomit in 53.8% and edema of the lower limbs in 60%. The most
      frequent age was in the third decade of life, and in the third trimester of
      pregnancy for all the cases, the main complication was acute renal insufficiency
      in 80% on the patients. Three patients died (20%), the causes were ARDS, brain
      hemorrhage and hypovolemic shock.

PMID- 7821830
TI  - [IUD insertion during cesarean section and its most frequent complications].
AB  - A prospective and cooperative study was done in 152 patients that were submitted
      to cesarean section. Seventy eight patients received intrauterine device (IUD) T
      CU 220 during cesarean section, and the other 74 patients only got the cesarean
      section without IUD. The events that were analyzed during the puerperium were
      pain, bleeding and infection. We didn't find any difference in the results
      between both groups, these were analyzed with the help of the square chi (X2).
      These results suggest that with an adequate selection of the patients, the
      insertion of the IUD during the cesarean section is a secure and helpful method
      for the fertility control for patients with high risk of reproduction.

PMID- 7821831
TI  - [Disseminated peritoneal leiomyomatosis with malignant degeneration. A case
      report].
AB  - Leiomyomatosis peritonealis disseminata (LPD), is a rare condition of unknown
      cause, characterized by the development of numerous nodules throughout the
      peritoneal cavity which appear during reproductive age, especially with pregnancy
      or associated with prolonged exposure to oral contraceptive agents.
      Histologically the nodules have the appearance of benign leiomyomata. LPD is
      thought to have originated from metaplasia of submesothelial multipotential
      mesenchymal cells. The treatment of the this disorder has been surgical
      castration, presumably to remove the hormonal stimulus necessary for tumor
      growth. Only two cases of malignant leiomyomatosis peritonealis disseminata have
      been reported. We report one more case of LPD with malignant degeneration which
      appears to be extremely rare.

PMID- 7821832
TI  - [Uterine estrogen sulfotransferase and estrogen sulfatase in embryo
      implantation].
AB  - The relation conjugated/unconjugated estrogens associated with reproductive
      processes has brought about the interest to study the biological role and
      regulation of the estrogen sulfotransferase and estrogen sulfatase which
      participate in the formation and hydrolysis of estrogen 3-sulfates, respectively.
      In this paper, both activities were measured through the reciprocal conversion of
      3H-estrone sulfate and 3H-unconjugated estrogen during in vitro incubation with
      implantation sites (SI) and non-implanted sites (SNI) from the rat uterus, during
      the process of embryo implantation. Contrasting enzyme activities were found in
      these tissues. While sulfotransferase activity was higher in SI than in SNI
      (0.205 vs 0.144 pmol of E1S formed/mg protein/h, the inverse was found for the
      sulfatase (1.470 vs 1.977 pmol of E1 formed/mg protein/h). These results indicate
      the presence of both enzymes in the rat uterus and suggest the existence of a
      mechanism in SI that locally regulate the concentration of free and
      sulfoconjugated estrogens in which these enzymes participate.

PMID- 7821834
TI  - [A simplified method in determination of blood 17-hydroxyprogesterone by
      radioimmunoanalysis].
AB  - A practical method to measure 17-OHP, in peripheral blood by radioimmunoanalysis
      using a highly specific antiserum, is described. The method usefulness described
      in dependability studies present a sensitivity of the pattern curve of 10
      picograms; precision shows a variation rate intranalysis < or = 11.9% and
      interanalysis of < or = 10.0%. Accuracy was > or = 95% and specificity is
      demonstrated by antiserum characterization with other steroids. Measuring 17-OHP4
      in ng/ml in plasma of women under different physiological conditions, it was
      found that the levels of this hormone on day -5 of proliferative phase were 0.31
      +/- 0.24 nanograms (ng)/ml, and at day +7 of secretory phase of 1.47 +/- 0.65
      ng/ml. In patients with stimulation with ACTH show as to the basal sample an
      increase (double) of levels at 30 minutes, that keeps increasing until 90 minutes
      with certain trend to diminish at 120 minutes. This study shows that it is
      possible, to measure 17-OHP4 in human plasma with good dependability degree and
      easy handling reducing, in addition, operative cost.

PMID- 7821833
TI  - [Treatment of puerperal endometritis. Evaluation of the efficacy and safety of
      clindamycin + gentamycin vs. penicillin + chloramphenicol + gentamycin].
AB  - This was a prospective, single-blind, comparative study in patients with
      diagnosis of puerperal endometritis, carried out at the Loayza Hospital in Lima,
      Peru. The objective of this study was to evaluate the efficacy and safety of
      clindamycin and gentamicin in the management of endometritis vs. penicillin,
      chloramphenicol and gentamicin for 10 days. Sixty-five patients were enrolled and
      62 were evaluable for efficacy. Both treatment groups were comparable in the pre
      treatment period in terms of age, history of pregnancies, controls by
      gynecologist, days of disease and fever, clinical symptoms like fever, pelvic
      pain, pulse, uterine size and in laboratory, in hematocrit and leukocytes count.
      In the culture of endometrium tissue, 27/32 patients (84.4%) in Group A
      (penicillin + CAF + gentamicin) and 27/30 patients (90%) in Group B (clindamycin
      + gentamicin) had positive cultures at baseline; 18 and 22 patients showed
      anaerobes; 8 and 4 patients showed anaerobes plus aerobes and, one patient in
      each treatment group showed aerobes only. Peptostreptococcus and Bacteroides
      fragilis were the most frequently isolated pathogens. Improvement in lochia
      fetidity was more rapid in Group B, it turned transparent and not fetid since day
      3. Complete cure was significantly better in Group B 24/30 (80%) in comparison
      with Group A 16/32 (50%) (p = 0.02). Partial response was found in 15 patients
      (43.3%) in Group A and 5 patients (16.6%) in Group B. Only one case was
      considered as bacteriological failure in Group A and only one patient in Group B
      was considered as failure and required an additional operation due to residual
      abscess.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7821835
TI  - [Typhoid fever in pregnancy. Clinical course, treatment and perinatal
      repercussions].
AB  - In Mexico typhoid fever (TF) is still a disease of major importance. The reports
      of TF complicating pregnancy are few in number, nevertheless the majority of
      authors agree than pregnancy does not alter the clinical presentation or the
      laboratory findings of the patient with TF. In these cases data suggest
      unfavorable perinatal outcome with a greater frequency of abortions and premature
      delivery. We report five cases of TF complicating pregnancy; one patient aborted,
      one had a preterm labor with neonatal dead of the product, and the other three
      had a normal pregnancy without abnormalities of the newborns. An improved outcome
      of the pregnant women complicated with TF is associated with a proper diagnosis
      and early treatment with ampicillin of ceftriaxone. Chloramphenicol is
      contraindicated during pregnancy.

PMID- 7821836
TI  - [Evaluation of sensitivity and specificity of 3 reagents of direct
      immunofluorescence in the diagnosis of Chlamydia trachomatis].
AB  - The sensitivity, specificity, positive and negative predictive values and
      positive and negative false percentage of three monoclonal immunofluorescence
      reagents for direct diagnosis of Chlamydia trachomatis infections were evaluated,
      150 cervical specimens and 50 samples of peritoneal liquid of patients with
      pelvic inflammatory disease, were studied. The results showed that the reagents
      against the main protein of external membrane of Chlamydia introduced high
      sensitivity but minor specificity than the reagent of immunofluorescence direct
      against then chlamydial lipopolysaccharide.

PMID- 7821837
TI  - Ovarian function after radical hysterectomy.

PMID- 7821838
TI  - Squamous cell carcinoma of the cervix metastatic to a drain site.
AB  - A squamous cell carcinoma of the cervix metastatic to the skin at the site of a
      previous retroperitoneal drain is detailed. A review of the literature concerning
      skin metastases in cervical cancer is also presented. This is the only case the
      authors can find in the literature of squamous carcinoma of cervix metastasizing
      to a drain site.

PMID- 7821839
TI  - Taxol as salvage therapy for epithelial ovarian cancer.

PMID- 7821840
TI  - Adjuvant therapy in cervical cancer.

PMID- 7821841
TI  - Problem of the patient with the abnormal pap smear, in whom a colposcopy and an
      ECC is negative.

PMID- 7821842
TI  - The role of serum tetranectin, CA 125, and a combined index as tumor markers in
      women with pelvic tumors.
AB  - Serum tetranectin (Se-TN) and CA-125 were measured in 315 patients with a pelvic
      tumor and 458 healthy females. At a false-positive rate of 0.7% the sensitivity
      for ovarian cancer stage 1 and 2 was 33% for Se-TN and 76% for both CA 125 and an
      index based on Se-TN and CA 125 (Index 1). At a false-positive rate of 0.4% the
      sensitivity was 29% for Se-TN, 62% for CA 125 (35 U/ml), and 76% for Index 1. A
      negative correlation was found between the Se-TN level and the stage of cancer.
      The sensitivity for benign tumors was 6% for Se-TN, 17% for CA 125, and 21% for
      Index 1 at a false-positive rate of 0.4%. In the present study the sensitivity
      and specificity levels of Se-TN were not sufficiently high to warrant the use of
      Se-TN as an individual marker for ovarian cancer. The sensitivity rose with the
      index-based Se-TN and CA 125 without causing a concomitant increase in the rate
      of false-positive results. None of the markers rose to levels that would allow
      their use in clinical diagnosis to discriminate between localized cancer and
      benign tumors.

PMID- 7821843
TI  - Adenocarcinoma of the endometrium: survival comparisons of patients with and
      without pelvic node sampling.
AB  - From 1969 to 1990, 649 patients with adenocarcinoma of the endometrium were
      surgically managed by gynecologic oncologists from the University of Alabama at
      Birmingham. All patients underwent TAH-BSO and washings. Two hundred twelve
      patients had multiple-site pelvic node sampling (mean number of nodes, 11), 205
      patients had limited site pelvic node sampling (mean number of nodes, 4), and in
      208 patients, nodes were not sampled. Historical prognostic features, including
      tumor grade, depth of invasion, adnexal metastasis, cervical involvement, and
      positive cytology, were equally distributed in the three groups. Mean follow-up
      was 3 years. Patients undergoing multiple-site pelvic node sampling had
      significantly better survival than patients without node sampling (P = 0.0002).
      When patients were categorized as low risk (disease confined to the corpus) or as
      high risk (disease in the cervix, adnexa, uterine serosa, or washings) multiple
      site pelvic node sampling again provided a significant survival advantage
      compared to patients without node sampling (high risk, P = 0.0006; low risk, P =
      0.026). In a comparison of patients receiving whole pelvic radiation for grade
      III lesions or deep myometrial invasion, patients with multiple-site pelvic node
      sampling had better survival than those in whom nodes were not sampled (P =
      0.0027). The significant survival advantage for patients having multiple-site
      node sampling, overall and in high- and low-risk groups, strongly suggests a
      therapeutic benefit. Additionally, adjuvant therapy may be more appropriate
      directed in these patients.

PMID- 7821844
TI  - The fate of the ovaries after radical hysterectomy and ovarian transposition.
AB  - To assess the effectiveness of lateral ovarian transposition in preserving normal
      ovarian function, the medical records of 200 consecutive women with stage I-IIA
      cervical cancer treated primarily with radical hysterectomy and pelvic
      lymphadenectomy were reviewed. Lateral ovarian transposition was performed at the
      time of radical hysterectomy in 132 (66%) patients and 28 (21%) received
      postoperative pelvic radiation therapy. Menopausal symptoms (vaginal dryness, hot
      flushes) and follicle-stimulating hormone (FSH) levels were used to define
      ovarian function. Only 3/104 (2.9%) patients who underwent lateral ovarian
      transposition without postoperative pelvic radiotherapy experienced menopausal
      symptoms; however, FSH levels in all three cases suggested continued ovarian
      function. In 14/28 (50%) patients who received postoperative pelvic radiation
      therapy ovarian failure occurred. The risk of ovarian failure with pelvic
      radiation therapy after lateral ovarian transposition was significant (RR = 17.3;
      95% CI = 5.35-56.13). The incidence of adnexal disease in transposed ovaries
      requiring analgesics or further surgery was 3%. These data suggest minimal risk
      to the patient when the ovaries are conserved. Unfortunately, lateral ovarian
      transposition preserves ovarian function in only 50% of patients undergoing
      pelvic radiotherapy following radical hysterectomy.

PMID- 7821845
TI  - Staging laparotomy for endometrial carcinoma: assessment of peritoneal spread.
AB  - To evaluate surgical staging procedures in women with endometrial carcinoma, we
      examined the techniques used to assess the peritoneal cavity in 295 clinical
      stage I patients treated between 1985 and 1993. These patients were felt to be at
      increased risk for extrauterine disease because of significant myometrial
      invasion, high-grade (2 or 3), or variant histology (papillary serous, clear
      cell, or mixed). Patients had a mean of two intraperitoneal samples taken: 224
      patients (76%) had at least an omental biopsy and peritoneal cytology. Additional
      peritoneal biopsy sites included pericolic gutters (50), pelvic peritoneum (45),
      bowel serosa/mesentery (24), diaphragm (22), appendix (11), and adhesions (7). At
      the time of staging laparotomy, 22 patients (7.5%) had gross evidence of
      peritoneal spread, which was readily confirmed by directed biopsy. In the 273
      women without gross peritoneal disease, 3 (1%) had occult metastases detected by
      routine biopsy, 3 (1%) had microscopic metastases in palpably abnormal biopsies,
      and 22 had positive cytology as the only evidence of peritoneal disease. Only
      three operative complications were potentially attributable to peritoneal
      assessment: cystotomy (1), partial small bowel obstruction (1), and ileus (1).
      Peritoneal failures have been noted in 12 patients over a mean follow-up interval
      of 39 months. Seven of these patients had obvious peritoneal disease at
      laparotomy. Two of the remaining 5 had optimal peritoneal sampling and represent
      false-negative cases. A staging laparotomy that included total abdominal
      hysterectomy with adnexal resection, cytology, omental biopsy, and biopsy of
      grossly abnormal sites would have potentially identified all patients with known
      peritoneal disease. Routine biopsy of other grossly normal peritoneal sites is
      associated with extremely low yield and is not recommended.

PMID- 7821846
TI  - Isolation and preliminary characterization of an ovarian carcinoma cell line from
      a patient with familial ovarian cancer.
AB  - An epithelial ovarian cancer cell line is established from a patient with
      recurrent familial ovarian cancer. Two of the patient's sisters and her mother
      have also had ovarian cancer. The histological resemblance of the cell line to
      the patient's Stage IV, Grade 3 papillary serous ovarian primary cancer is
      striking. The cell line does not secrete CA125 and is estrogen and progesterone
      receptor negative. Overexpression of the p53 tumor suppressor gene but not the
      HER-2/neu oncogene was detected by immunohistochemical analysis. An unusual
      chemosensitivity to cisplatin, doxorubicin, etoposide, and taxol is demonstrated,
      suggesting that a chemosensitivity mechanism might explain prolonged survival of
      some patients with familial ovarian cancers. This truly unique cell line should
      prove invaluable in the further evaluation of molecular genetic changes
      associated with familial ovarian cancers.

PMID- 7821847
TI  - A 30-year experience in the management of primary carcinoma of the vagina:
      analysis of prognostic factors and treatment modalities.
AB  - This retrospective study of 100 cases of primary carcinoma of the vagina treated
      at Magee-Women's Hospital of the University of Pittsburgh from 1962 to 1992
      analyzes disease and treatment-related prognostic factors and treatment results.
      Fifty percent of patients had previous hysterectomies prior to the diagnosis of
      vaginal cancer. The tumor was limited to one-third of the vaginal canal in 64
      patients, but involved more than one-third of the canal in 36 patients. Treatment
      consisted of surgery in 40 patients, radiation therapy in 47 patients, and
      surgery plus radiation therapy in 13 patients. With a median follow-up of 11.2
      years, the 5-year actuarial disease-free survival (DFS) was 67% for Stage I (23
      patients), 53% for Stage II (58 patients), 0% for Stage III (9 patients), and 15%
      for Stage IV (10 patients). Using univariate and multivariate analysis, treatment
      with surgery, disease limited to one-third of the vaginal canal, and FIGO Stage I
      and II disease were significantly favorable prognostic factors for DFS. Treatment
      with surgery was superior to radiation therapy alone in Stage II patients (P =
      0.00004). There appeared to be a selection bias in Stage II patients, as the more
      unfavorable cases were treated with radiation therapy. Although radiation therapy
      will often be the treatment of choice, excellent results and limited morbidity
      accompany selected cases surgically resected.

PMID- 7821848
TI  - Characterization and radiosensitivity of UT-EC-2A and UT-EC-2B, two new highly
      radiosensitive endometrial cancer cell lines derived from a primary and
      metastatic tumor of the same patient.
AB  - UT-EC-2A was established from a patient with moderately differentiated Stage III
      endometrial adenocarcinoma with squamous metaplasia. UT-EC-2B was established
      from the same patient 17 months later from a metastasis in the left
      supraclavicular fossa. The origin of these cell lines was confirmed by DNA
      identity testing. Nude mice tumors produced by UT-EC-2A and UT-EC-2B cells
      recapitulated the histology of the original human tumors. Flow cytometric DNA
      contents of both primary and metastatic human tumors as well as corresponding
      nude mice tumors were diploid. The S-phase fractions of both cell lines were > or
      = 30%. The UT-EC-2A cell line was cytogenetically normal. The UT-EC-2B cell line
      had quite simple karyotype at low passage with an extra i(18p) and a deletion
      21q, but at higher passages an additional three-way translocation 5;14;19 was
      observed. Radiosensitivity of the cell lines was tested with the 96-well plate
      clonogenic assay. The areas under the survival curves corresponding to the mean
      inactivation doses of UT-EC-2A and UT-EC-2B were 0.65 +/- 0.10 and 0.60 +/- 0.06
      Gy, respectively. Measured survival at 2.0 Gy (SF2) was 0.042 for UT-EC-2A, 0.044
      for UT-EC-2B, and 0.2 for skin fibroblasts. These cell lines are among the most
      radiosensitive human cancer cell lines described in the literature. Studying the
      characteristics of primary and metastatic cells derived from the same patient
      provides an opportunity to evaluate tumor progression.

PMID- 7821849
TI  - A clinicopathologic study of 30 patients with Paget's disease of the vulva.
AB  - Clinical and pathologic analyses were performed in 30 patients with Paget's
      disease of the vulva to investigate the risk factors for recurrence. From 1971 to
      1993, we carried out histologic examinations in 27 resected vulvae to detect
      Paget's cells at the surgical margin. Prior to 1981, 9 patients underwent the
      examination, and 6 of them had positive surgical margins, and 2 of these 6
      patients had local recurrence. After 1982, the preoperative multiple biopsy and
      intraoperative frozen section diagnosis of the surgical margins were performed,
      and as a result, cases of the lesions remaining as stumps on the vaginal side
      decreased in 7 of 18 examined patients. In these 7 cases, 2 cases had local
      recurrence. The patients were further divided into three groups according to
      histologic findings to investigate their prognosis: 10 patients with
      intraepithelial Paget's disease (IEP), 9 patients with minimally invasive Paget's
      disease (MIP), and 11 patients with underlying carcinoma (UC) including 2 cases
      of carcinoma in situ. Four locally recurrent cases were found in IEP or MIP, and
      the longest period from surgery to recurrence was 8 years and 4 months. The
      invasive UC lesions persisted or recurred shortly after surgery (median, 10
      months) and 5 of the 6 patients with general metastasis. For IEP and MIP,
      surgical margins of the vaginal side should be carefully examined with
      preoperative multiple biopsy and intraoperative frozen section, and also a long
      term follow-up is necessary. With regard to invasive UC patients, their prognosis
      was found to be very poor for general metastasis.

PMID- 7821850
TI  - A follow-up study of patients with cervical cancer after resection, with special
      emphasis on the incidence of second primary cancers.
AB  - The causes of death in long-term survivors after resection of cervical cancer
      were investigated in a follow-up study of 375 women, focusing especially on the
      postoperative development of second primary cancers. The 5- and 10-year overall
      survival rates were 75.0 and 66.0%, respectively, in cases that showed frank
      invasion, 94.7 and 92.8%, respectively, in those showing microinvasion, and 96.2
      and 96.2% respectively, in those showing carcinoma in situ. Multivariate analysis
      identified patient age and cancer stage at the time of diagnosis as separate
      factors prognostic for overall survival. During the observation period, 10
      patients developed a second primary cancer, but no significantly elevated risk of
      developing a second primary cancer was demonstrated. However, during the same
      period, 20 patients also died of noncancerous disease, 9 of this number
      succumbing to acute myocardial infarction and/or heart failure. These results
      suggest that patients with cervical cancer may not have an increased risk of
      developing second primary cancer. It is felt that continued follow-up of long
      term cervical cancer survivors should be pursued in order to prevent or arrest
      the development of noncancerous disease and/or second primary cancer, so that
      increased prolongation of survival can be achieved.

PMID- 7821851
TI  - A phase 2 trial of ifosfamide/mesna as salvage therapy in patients with ovarian
      cancer refractory to or relapsing after prior platinum-containing chemotherapy.
AB  - Continuous 24-hr infusion of ifosfamide (IFX) with mesna was studied in 19
      patients with advanced epithelial ovarian cancer refractory to or recurrent after
      platinum-containing chemotherapy. The patients received IFX 5 g/m2 as a 24-hr
      i.v. infusion. Mesna (total dose 8 g/m2) was given i.v. 3 hr before, together
      with, and 0 and 6 hr after IFX infusion, respectively. Cytotoxic therapy was
      repeated every 4 weeks. Of 19 evaluable patients, none achieved a complete
      response, 2 showed a partial response, and 8 had stable disease. Median survival
      for all patients was 6 months, and median time to progression was 4 months.
      Toxicity was moderate. Leucopenia WHO grade III-IV was observed in 3 patients.
      Thrombocytopenia WHO grade III-IV was not observed. Nausea/vomiting WHO grade III
      IV occurred in 8 patients. One patient experienced mild reversible confusion. No
      patients had macro-or microscopic hematuria and there was no deterioration of
      renal function. We conclude that IFX given as a 24-hr infusion is moderately well
      tolerated, but has only limited activity in patients with ovarian cancer
      refractory to or relapsing after prior platinum-containing chemotherapy.

PMID- 7821852
TI  - Smoking, obesity, and survival in squamous cell carcinoma of the vulva.
AB  - One hundred thirty-six patients with invasive squamous cell carcinoma of the
      vulva were studied retrospectively to determine prognostic factors for survival.
      In the regression analysis, three variables were statistically significantly
      related to survival: smoking history, tumor size, and node status. Smokers had a
      6.3 times greater risk than nonsmokers, node positivity imparted an 8.3 times
      greater risk than node negativity, and for each 1-cm increase in the size of the
      tumor, the risk of death increased by 46%. A relative decrease in survival in
      smokers was observed, despite a younger age and fewer positive nodes at diagnosis
      compared to nonsmokers. Increased surveillance in these patients may be
      warranted.

PMID- 7821853
TI  - Intraepithelial neoplasia of the vulva.
AB  - Intraepithelial neoplasia of the vulva is being seen with increasing frequency.
      Awareness of this should prompt the clinician to carefully inspect the vulva on
      all patients. Reports strongly suggest a relationship between infection with
      human papillomavirus and vulvar intraepithelial neoplasia. The frequency with
      which this disease progresses to invasive carcinoma is unknown at present.
      However, it is obvious that it does occur. Both the warty and basaloid types of
      vulvar intraepithelial neoplasia are associated with HPV infection and are often
      associated with invasive squamous cell carcinoma of the vulva demonstrating
      similar morphologic characteristics. These changes are seen more often in younger
      women who smoke than in the older nonsmoking woman whose lesions do not appear to
      be HPV related. Both local excision and the carbon dioxide laser are effective
      for treating vulvar intraepithelial neoplasia. The choice of which approach to
      take depends upon the location and size of the lesion or lesions. Whichever
      approach is utilized, preservation of the normal vulvar anatomy and function are
      of paramount importance.

PMID- 7821854
TI  - Leiomyosarcoma of the broad ligament: a case report and literature review.
AB  - Solitary tumors of the broad ligament are rare. The most frequent solid tumor of
      the broad ligament is leiomyoma. Leiomyosarcoma of the broad ligament (LBL) is an
      extremely rare malignant tumor. Nine cases of leiomyosarcoma of the broad
      ligament had been reported previously. A 59-year-old woman with LBL is reported.
      Treatment consisted of resection and total abdominal hysterectomy with bilateral
      salpingo-oophorectomy. No evidence of metastasis is noted after 12 months follow
      up. We conclude that the management of LBL is excision of the leiomyosarcoma as
      completely as possible and postoperative adjuvant chemotherapy.

PMID- 7821855
TI  - A complete hydatidiform mole coexisting with a normal fetus was confirmed by
      variable number tandem repeat (VNTR) polymorphism analysis using polymerase chain
      reaction.
AB  - The diagnosis of a complete hydatidiform mole coexisting with a live fetus is
      often difficult because of the morphological similarity to a partial mole, but it
      is crucial to management in the postmolar course. We present a recent case in
      which DNA polymorphism analysis clearly revealed a different genetic origin for
      the fetal and molar parts. DNA polymorphisms on three different variable number
      tandem repeat loci, which were detected by polymerase chain reaction, indicated
      that the cord/placenta and molar tissue were parental and androgenetic,
      respectively. Subsequently, the patient was admitted for chemotherapy of
      metastatic trophoblastic disease.

PMID- 7821856
TI  - Foreign body reaction (gossypiboma) masking as recurrent ovarian cancer.
AB  - Surgical is an absorbable sterile mesh composed of oxidized cellulose used to
      control capillary or venous bleeding. Although the manufacturer recommends its
      removal after hemostasis is achieved, in clinical practice it is usually left in
      situ to reabsorb spontaneously, usually with no untoward effect. We report the
      first case of foreign body reaction (gossypiboma) masking as recurrent malignancy
      discovered 13 months post-cytoreductive surgery for ovarian carcinoma.

PMID- 7821857
TI  - Mature cystic teratomas of the ovary with intestinal wall structures harboring
      intestinal- type epithelial neoplasms.
AB  - Mature cystic teratomas of the ovary frequently contain intestinal-type tissues,
      but these rarely organize into complete intestinal walls, including all layers,
      and even more rarely develop secondary neoplasms. The present report documents
      two mature teratomas with formation of complete segments of intestinal wall, one
      also containing a benign mucinous cystadenoma of the appendiceal type and the
      other an intestinal-type adenocarcinoma infiltrating into the neoplastic bowel
      wall but not the surrounding ovarian parenchyma. The latter patient is alive and
      well 5 years after surgery. These cases expand the repertoire of secondary
      neoplasms, benign and malignant, developing in mature cystic teratomas.

PMID- 7821858
TI  - [The basic aspects and principles of gene therapy].

PMID- 7821859
TI  - [Dermatoses in pregnancy].

PMID- 7821860
TI  - [Genetic dermatoses in gynecology and obstetrics].

PMID- 7821861
TI  - [Prenatal diagnosis of genetic dermatoses].

PMID- 7821862
TI  - [Differential diagnosis of hair loss in women].

PMID- 7821863
TI  - [Acne].

PMID- 7821864
TI  - [Malignant melanoma with special reference to gynecologic aspects].

PMID- 7821865
TI  - [Allergic and pseudoallergic drug reactions].

PMID- 7821866
TI  - [Allergies to latex gloves. What is the significance and what the gynecologist
      should consider].

PMID- 7821867
TI  - [Drug therapy in gynecology and obstetrics in inducible porphyria].

PMID- 7821868
TI  - [Fatal amniotic fluid embolism 20 hours after secondary cesarean section].

PMID- 7821869
TI  - [The child as damage].

PMID- 7821870
TI  - Effects of a dietary load of acid or base on changes induced by lactose in rats.
AB  - Feeding lactose or other slowly digestible carbohydrates to adult mammals may
      induce a variety of effects including hyperplasia and neoplasia. The most
      fundamental effect probably is the increased production in the large intestine of
      short-chain fatty acids (SCFA) resulting from increased fermentation of
      carbohydrate residues. To find out whether the increased production of these
      acidic compounds is involved in the induction of certain alterations caused by
      low-digestibility carbohydrates, the modifying effects of an acidifying (NH4Cl)
      or an alkalizing (KHCO3) diet supplement on lactose-induced changes in rats were
      studied. Three groups of 50 rats per sex were fed a 20% lactose diet
      unsupplemented or supplemented with 1% NH4Cl or 2% KHCO3, for at most 2.5 yr. One
      control group was fed the basal diet which contained wheat starch instead of
      lactose. Feeding lactose resulted in wet faecal pellets, reduced pH of the
      faeces, higher intake of food and water, lower body weights, increased caecal
      weights and fewer deaths. These effects were not significantly modified by NH4Cl
      or KHCO3. Feeding lactose increased urinary calcium levels, the effect being
      enhanced by NH4Cl and reduced by KHCO3. Lactose also tended to increase blood
      values of alkaline phosphatase and to decrease those for bicarbonate and base
      excess. These tendencies were generally more marked with NH4Cl, and less marked
      or absent with KHCO3. In addition, rats fed lactose showed decreased severity of
      nephrosis, increased mineralization and hyperplasia of the renal pelvic
      epithelium, and relatively high incidences of Leydig cell hyperplasia and
      neoplasia. NH4Cl supplementation was associated with a relatively small number of
      single and multiple tumours, with decreased incidences of hyperplasia and
      mineralization of the renal pelvis epithelium and with a markedly reduced
      incidence of proliferative changes in the adrenal medulla. With the KHCO3
      supplement the incidences of Leydig cell proliferation and of bladder tumours
      were relatively high. These findings, in particular the differences between the
      diet groups in urinary calcium levels and possibly also the variations in blood
      levels of alkaline phosphatase, bicarbonate and base excess, suggest that the
      acidic end products of carbohydrate fermentation (SCFA) act as an acid load on
      the body.

PMID- 7821871
TI  - Analysis of the potential carcinogenicity of coffee and its related compounds in
      a medium-term liver bioassay of rats.
AB  - The potential carcinogenicity of coffee and related compounds was examined using
      a medium-term liver bioassay based on the induction of glutathione S-transferase
      placental form (GST-P)-positive foci in F344 rats. A total of 230 males were
      initially injected with diethylnitrosamine (200 mg/kg body weight, ip) or saline
      as controls and 2 wk later were fed on diet or drinking water supplemented as
      follows for 6 wk: 5% regular instant coffee; 5% decaffeinated instant coffee;
      freshly brewed coffee, 8 g in 140 ml water; 0.1% caffeine, 0.2% methylglyoxal,
      0.2% glyoxal; or 0.3% theophylline in the drinking water (w/v); and 0.4%
      theobromine in the diet (w/w). All rats were subjected to two-thirds partial
      hepatectomy at wk 3 and killed at wk 8. The resultant values for GST-P-positive
      hepatic focus induction were slightly increased with methylglyoxal and decreased
      with glyoxal and theobromine compared with the corresponding controls. Although
      the increase in number of foci for methylglyoxal was statistically significant at
      P < 0.05, the value was within the historical control levels. Regular and
      decaffeinated instant coffee as well as fresh-brewed coffee, caffeine and
      theophylline exerted no effects on focus development. Thus, the coffee-related
      compounds examined demonstrated no obvious enhancing potential, and it is
      therefore concluded that coffee and its main constituents are not carcinogenic
      for the rat liver.

PMID- 7821872
TI  - Effects of caffeine on glandular stomach carcinogenesis induced in rats by N
      methyl-N'-nitro-N-nitrosoguanidine and sodium chloride.
AB  - The modifying effects of caffeine ingestion on glandular stomach carcinogenesis
      induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and sodium chloride (NaCl)
      were investigated in male Wistar rats. Animals were given a MNNG solution (100
      ppm) as their drinking water and simultaneously fed a diet supplemented with 5%
      NaCl for 8 wk. They then received 0.25% caffeine solution (groups 1 and 3) or tap
      water (groups 2 and 4) as the drinking water, and were fed the NaCl diet (groups
      1 and 2) or basal diet (groups 3 and 4) for the following 32 wk. Both caffeine
      and NaCl treatments exerted growth retardation effects, the suppression being
      stronger with caffeine than NaCl, and animals in group 1 (NaCl plus caffeine)
      showing the lowest body weight. The incidence of adenocarcinomas in the pylorus
      was significantly decreased in group 1 compared with the group 2 (NaCl) value (P
      < 0.05). The incidence of atypical hyperplasias in the fundus was also lower in
      group 1 than in group 2, although in both cases significantly higher (P < 0.05
      and P < 0.01) than in group 4 (no treatment). These results were in good
      agreement with short-term assay findings whereby lipid peroxidation in the
      glandular stomach mucosa induced by 4% NaCl ingestion was inhibited by caffeine
      treatment. In group 3 (caffeine), caffeine intake by itself did not modulate
      glandular stomach tumour development. The results thus suggest that caffeine
      inhibits the gastric tumour promotion activity of NaCl in rats.

PMID- 7821873
TI  - Stimulation of rat hepatic UDP-glucuronosyl transferase activity following
      treatment with green tea.
AB  - Studies were conducted to investigate whether aqueous extracts of green tea,
      administered to rats at concentrations consumed by humans, could influence the
      phase II conjugation reactions in the liver, and so contribute to its established
      anticarcinogenic activity. Exposure of rats to green tea (2.5%, w/v), as the sole
      drinking fluid, for 4 wk did not influence sulfotransferase, epoxide hydrolase
      nor glutathione S-transferase activities. UDP glucuronosyl transferase activity,
      when determined using 2-aminophenol as the substrate, was increased by 100%
      following treatment with tea. Finally, green tea had no effect on the enzymes
      affording protection against reactive oxygen species, namely catalase,
      glutathione peroxidase and superoxide dismutase. It is postulated that the
      enhanced glucuronidation may contribute to the anticarcinogenic effect of green
      tea by facilitating the metabolism of chemical carcinogens into inactive, readily
      excretable products.

PMID- 7821874
TI  - Cytotoxic and clastogenic effects of benzyl isothiocyanate towards cultured
      mammalian cells.
AB  - Benzyl isothiocyanate (BITC), a compound found in cruciferous vegetables present
      in the human diet, has previously been shown to induce chromosome aberrations in
      an Indian muntjac cell line. The results of this study show that it also induces
      both chromosome aberrations and sister chromatid exchanges (SCEs) in Chinese
      hamster ovary (CHO) cells in the absence of an exogenous metabolic activation
      system and induces DNA strand breaks as measured by the single-cell gel
      electrophoresis assay. However, whereas it increased the number of aberrations
      four-fold, it was not able to raise SCE levels by more than 50% and there was a
      levelling-off in the dose-response curve. Whereas the survival curve of CHO cells
      exposed to BITC was linear in shape, that of the human colorectal adenocarcinoma
      cell line HT29 was found to fit the exponential model (with an alpha equivalent
      of 0.28 and a beta equivalent of 2.80, where the concentration of BITC is
      measured in micrograms/ml). This pattern of clastogenic and cytotoxic activities
      is reminiscent of that generated by ionizing radiation and certain radiomimetic
      chemotherapeutic agents.

PMID- 7821875
TI  - Toxicological studies on ratanjyot oil.
AB  - Ratanjyot (Jatropha curcas) grows wild in many parts of India and Brazil.
      Experimental studies on the toxicity of its oil are scarce despite its use as a
      cathartic purgative, for treatment of many ailments in human medicine and in
      industrial applications. This study aims to provide data on its toxicity. The
      proximate composition of the kernels and physicochemical characteristics of its
      oil were determined. The kernels constitute 62% of the seed and contain 52% oil,
      which is reported to contain phorbol esters. A toxic fraction (2.4%) containing
      the phorbol esters was isolated from the oil. The acute oral LD50 of the oil was
      found to be 6 ml/kg body weight in rats. The oil caused severe diarrhoea and
      gastro-intestinal inflammation. The isolated toxic fraction, when applied to the
      skin of rabbits and rats, produced a severely irritant reaction followed by
      necrosis; in mice, this fraction had a dermally toxic and lethal effect. The oil
      and the toxic fraction at 25 and 1 mg respectively in 10 ml saline showed
      haemolytic activity, disrupting red blood cells. Detoxification or complete
      removal of the potent toxins present in ratanjyot oil is essential before its use
      in industrial applications or in human medicine can be considered.

PMID- 7821876
TI  - Nitrosation of Nigerian medicinal plant preparations under 'chemical' and
      'simulated' gastric conditions.
AB  - Preparations of some tropical plants of medicinal importance, collected from the
      savannah vegetational belt of Nigeria, were nitrosated and analysed for volatile
      N-nitrosamines formed under chemical and simulated gastric conditions. N
      Nitrosamines were determined on a Thermal Energy Analyser following gas
      chromatographic separation. Mean concentrations of N-nitrosodimethylamine (NDMA)
      in the range of 7 to 58 ppb and N-nitrosodiethylamine (NDEA) in the range of 23
      to 26 ppb were formed in 31 and 7%, respectively, of the preparations using
      artificial gastric juice (simulated gastric condition). Under chemically optimal
      conditions, relatively high levels of NDMA (72-2008 ppb), NDEA (23-1528 ppb) and
      N-nitrosopyrrolidine (20-405 ppb) were formed in 100, 75 and 32% of the
      preparations, respectively; N-nitrosomethylethylamine, N-nitrosodibutylamine and
      N-nitrosomorpholine were formed in fewer preparations. These findings suggest
      that the endogenous formation of N-nitroso compounds from precursors present in
      medicinal plants might be another source of human exposure to environmental
      carcinogens in Nigeria and other developing countries.

PMID- 7821877
TI  - Persistence of organochlorines in breast milk of women in Victoria, Australia.
AB  - Existing information on the exposure of Australian infants to environmental
      contaminants through maternal milk is inadequate for assessing the safety of
      breast feeding. This study was undertaken to determine the extent of
      organochlorine (OC) contamination in the milk of mothers resident in Victoria, to
      monitor OC elimination by the nursing mother and to estimate the infant's daily
      intake of OCs from breast milk. Organochlorines were extracted from the
      lipophilic fraction of the breast milk samples and analysed by selected ion
      monitoring on a gas chromatograph-mass spectrometer (GC-MS). There was widespread
      contamination of milk with dichlorodiphenyltrichloroethane (p,p'-DDT) and its
      metabolite dichlorodiphenyldichloroethene, hexachlorobenzene (HCB),
      polychlorinated biphenyls (PCBs), oxychlordane and hexachlorocyclohexane, with
      p,p'-DDT and HCB being found in nearly all samples. Dieldrin and heptachlor
      epoxide were detected in 43 and 30% of samples respectively. PCBs were detected
      in 79% of samples and chlordane in 76%. A number of infants had daily intakes
      above the acceptable daily intake for total chlordane, total DDT, dieldrin,
      heptachlor epoxide and total PCBs. These findings have implications for
      strategies for the reduction of environmental contamination.

PMID- 7821878
TI  - Effects of contact sensitizers neomycin sulfate, benzocaine and 2,4
      dinitrobenzene 1-sulfonate, sodium salt on viability, membrane integrity and IL-1
      alpha mRNA expression of cultured normal human keratinocytes.
AB  - The toxic effect of three potential contact sensitization chemicals [the
      aminoglycosidic antibiotic neomycin sulfate, the local anaesthetic benzocaine and
      the primary sensitizer 2,4-dinitrobenzene 1-sulfonate, sodium salt (DNBS)], on
      cultured human keratinocytes was examined. The three chemicals were compared with
      respect to their cytotoxic potential (determined by crystal violet staining
      assay), their membrane disruptive potential ([3H]arachidonic acid release assay),
      and their effects on interleukin 1 alpha (IL-1 alpha) mRNA expression [reverse
      transcription-polymerase chain reaction (RT-PCR)]. At the concentrations used,
      neomycin sulfate (0.004-0.32%) and benzocaine (0.0165-0.165%) did not show
      relevant cytotoxicity or membrane perturbation. On the other hand, DNBS (0.001
      1%) caused a significant dose-dependent cytotoxic response at concentrations
      higher than 0.1%, while the [3H]arachidonic acid release assay indicated absence
      of membrane perturbation activity in all the range of DNBS concentrations
      examined. The effects of the three sensitizers on IL-1 alpha mRNA expression were
      varied; neomycin sulfate caused a dose-dependent induction of IL-1 alpha mRNA,
      benzocaine did not significantly affect its signal, and DNBS suppressed IL-1
      alpha gene expression.

PMID- 7821879
TI  - Monosodium L-glutamate: a double-blind study and review.

PMID- 7821880
TI  - The very intolerant peanut.

PMID- 7821881
TI  - [Diagnosis of acute dissection of the thoracic aorta. Status of noninvasive
      methods].

PMID- 7821882
TI  - [Acupuncture inhibits secretion of gastric acid. Prospective randomized study
      series with various acupuncture procedures].

PMID- 7821883
TI  - [Differential diagnosis of "rheumatoid nodules"].
AB  - Rheumatic nodules occur in some 20 to 25% of cases of chronic polyarthritis, and
      need special diagnostic, in particular differential diagnostic, consideration.
      They have to be differentiated from numerous other nodules in rheumatoid and non
      rheumatoid diseases. To achieve this, palpation, a knowledge of the preferred
      sites, and the use of such technical means as laboratory and x-ray investigations
      are all useful.

PMID- 7821884
TI  - [Does methotrexate induce "rheumatoid nodules"? Case report and discussion of the
      literature].
AB  - A 58-year-old woman with chronic polyarthritis rapidly developed a large number
      of rheumatic nodules under treatment with methotrexate. A comparison with other
      cases reported to date showed that the sudden onset of such nodules after
      initiation of treatment, and their disappearance again after discontinuation of
      the drug make the causal relationship highly likely. Although the predominantly
      anti-inflammatory actions of methotrexate control the chronic polyarthritis in
      almost all cases so far reported, they are unable to prevent the primarily
      immunological tissue necrosis (rheumatic nodules) and may even promote their
      development through the liberation of adenosine. Only in very rare cases does the
      severity or localisation of the nodules--e.g. vasculitis, pulmonary or cardial
      manifestation--necessitate the discontinuation of methotrexate.

PMID- 7821885
TI  - [Diagnosis and therapy of tumor pain. 3: Centrally acting analgesics--opiates].

PMID- 7821887
TI  - Melanoses of the gastrointestinal tract.
AB  - Electronmicroscopy and electron probe energy dispersive X-ray analysis studies
      have substantially contributed to our understanding of the various
      gastrointestinal tract melanoses. The nature of the pigment granules which occur
      in the various melanoses is discussed; their pattern of distribution in melanosis
      coli, melanosis ilei, melanosis duodeni and melanosis oesophagi is summarized and
      current knowledge of the aetiology and pathogenesis of these conditions is
      reviewed. Brief mention is also made of other examples of lipofuscin
      pigmentation, and a case of haemosiderosis ilei is described.

PMID- 7821886
TI  - [Effect of acarbose on postprandial increase in blood glucose. Additive acute
      effect of once daily administration in insulin treated diabetes].
AB  - Only few controlled studies have been conducted on the influence of additive
      treatment with the glucosidase inhibitor acarbose on post-prandial blood sugar
      levels in insulin-dependent diabetics. To date, the behavior of blood sugar
      levels under treatment with acarbose has not been studied in insulin-dependent,
      type II diabetics. METHOD: Forty-six diabetics--36 insulin-dependent type II, and
      10 type I--were enrolled in a double-blind, placebo-controlled randomized
      parallel group study with the aim of investigating the influence of acarbose on
      the primary variable maximum blood glucose increase following a standard
      breakfast eaten after 7 days of treatment. The patients were to have an HbA1
      value of > 9%, and a post-prandial increase in blood glucose 90 minutes after a
      standardised breakfast (3 white bread units) of at least 50 mg/dl as compared
      with the fasting blood sugar during a one-week run-in period. INTERVENTION: The
      patients were randomized to treatment consisting of either one tablet of 100 mg
      acarbose or a single placebo tablet taken daily with breakfast. RESULTS: While
      the placebo group showed a mean further rise in maximum blood glucose levels
      after 7 days of treatment from 76.1 +/- 13.1 mg/dl to 84.3 +/- 17.8 mg/dl over
      the baseline value, there was a decrease in the acarbose group from 80.5 +/- 12.8
      to 46.3 +/- 12.8 mg/dl. The difference between the two groups was statistically
      significant (p = 0.0001). No significant correlation was found between the
      treatment and type of diabetes. Mild adverse events such as meteorism, flatulence
      and diarrhea did not lead to any interruption of the study, and had cleared up by
      the end of the trial in all patients. CONCLUSION: The use of a single dose of 100
      mg acarbose at breakfast time can result in a marked flattening of elevated post
      prandial morning blood glucose profiles in both insulin-dependent type II and
      type I diabetics.

PMID- 7821888
TI  - Guidelines for the diagnosis and interpretation of hepatic granulomas.

PMID- 7821889
TI  - Hepatic granulomas in Northern Ireland: a thirteen year review.
AB  - The finding of epithelioid cell granulomas within liver biopsies is a not
      uncommon occurrence. We undertook this study to investigate the underlying
      conditions responsible for a diagnosis of granulomatous hepatitis in Northern
      Ireland during the thirteen year period 1980-1992. One hundred and sixty-three
      patients with hepatic granulomas were identified, accounting for 4% of all liver
      biopsies undertaken during the period of the study. In 145 cases (89%) a definite
      clinical diagnosis was established. The most common clinical diagnoses were
      primary biliary cirrhosis which accounted for 90 cases (55%) and sarcoidosis
      which accounted for 30 cases (18%). Other less common conditions associated with
      hepatic granulomas included tuberculosis (3 cases), Crohn's disease (3 cases),
      chronic active hepatitis (2 cases), drug hypersensitivity (2 cases) and extra
      hepatic biliary obstruction (2 cases). Six patients were identified with a
      clinical diagnosis of psoriasis. Other miscellaneous conditions accounting for
      single examples of granulomatous inflammation were schistosomiasis, gout,
      Hodgkin's disease, secondary adenocarcinoma, collapse and necrosis of tumour
      following radiotherapy and chemotherapy, granulomatous inflammation within the
      wall of an abscess cavity and idiopathic cirrhosis. Only eighteen cases (11%)
      remained idiopathic with no definite diagnosis established after detailed
      investigation. The findings confirm the wide range of clinical conditions which
      can result in hepatic epithelioid cell granulomas. This has been emphasised in
      several previous major studies which are reviewed in this paper.

PMID- 7821890
TI  - Monoclonal antibody HML-1 reactivity with adult T-cell leukaemia/lymphoma and
      other lymphomas.
AB  - Human T-cell leukaemia/lymphoma virus type 1 (HTLV-1), a causative virus of adult
      T-cell leukaemia/lymphoma (ATLL), is known to be transmitted by breast-feeding.
      Using a monoclonal antibody HML-1 which labels human intestinal intra-epithelial
      T lymphocytes, we have immunohistochemically examined ATLL tissues in order to
      evaluate the possibility that HTLV-1 infected intestinal T cells are the origin
      of ATLL cells. Previously this antibody was reported to react with intestinal T
      cell malignant lymphomas but not with peripheral tumours, or any B-cell
      lymphomas. We investigated 181 patients with malignant lymphomas and found that
      19 out of 113 ATLLs were positive for HML-1. T-cell malignant lymphomas excluding
      ATLL also reacted with HML-1 (7/24), but all the B-cell lymphomas 0/33) and non
      neoplastic lymph node and skin lesions (0/10) were negative for HML-1. In
      patients with ATLL and other T-cell malignant lymphomas, the positivity level of
      HML-1 was relatively higher in stomach (3/7) and tonsil (2/6) than that in lymph
      nodes (15/100) and skin (8/47). We observed one HML-1 positive ATLL patient with
      tumour formation in the skin and lymphadenopathy and marked infiltration of the
      large intestine but minimal involvement of other organs. Although HML-1 was
      frequently expressed in gastric infiltration of ATLL, the level of positivity was
      too low in lymph nodes to support the hypothesis that HTLV-1 infected intestinal
      T cells are the origin of ATLL cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7821891
TI  - Immunohistochemical detection of bcl-2 protein in liver lesions: bcl-2 protein is
      expressed in hepatocellular carcinomas but not in liver cell dysplasia.
AB  - A proto-oncogene, bcl-2, encodes a protein that inhibits programmed cell death
      (apoptosis) and may play a role in cell and tissue differentiation. As bcl-2
      appears to be involved in the turn-over of stem or precursor cells, it is thought
      to be operational in carcinogenesis pathways. However, apart from certain
      lymphomas, only limited data are available on the frequency of its expression in
      solid tumors. Immunohistochemical analysis with an antibody specific for bcl-2
      protein was used to detect the protein in hepatocellular carcinomas and in one of
      the putative precursor lesions, liver cell dysplasia. We detected bcl-2 protein
      in 5 of 37 hepatocellular carcinomas. Immunoreactivity was not related to type,
      grade, or extent of PCNA staining of the tumours. No bcl-2 protein staining was
      observed in three types of liver cell dysplasia. Thus, bcl-2 is abnormally
      expressed in some hepatocellular carcinomas but not in potential tumour precursor
      cells.

PMID- 7821892
TI  - c-erbB-3 protein expression in human breast cancer: comparison with other tumour
      variables and survival.
AB  - c-erbB-3 protein expression was investigated immunohistochemically in a series of
      97 malignant breast tumours using the monoclonal antibody RTJ1. Twenty-eight
      cases (28.8%) showed c-erbB-3 overexpression, 31 cases (32%) showed normal levels
      of c-erbB-3 and 38 cases (39.2%) were c-erbB-3 negative. c-erbB-3 overexpression
      was positively but not significantly related to negative lymph node status and
      survival over a 10-year follow-up period.

PMID- 7821893
TI  - Integrated decision support system/image archive for histological typing of
      breast cancer using a relation oriented inference system.
AB  - Histological typing of invasive breast cancer according to the World Health
      Organisation criteria is prognostically relevant, because some histological
      subtypes have a markedly better prognosis. However, reproducibility of
      histological typing is not high because of the absence of strict typing criteria,
      variations in the application of the typing criteria and the usually limited
      illustration of the relevant criteria. The aim of this study was to develop an
      expert system based on highly structured histological typing criteria, integrated
      with high-quality microscope images to illustrate the typing criteria. This
      system should be useful as a decision support system in the diagnosis of breast
      cancers and should increase the reproducibility of histological typing. Criteria
      for typing were extracted from textbooks and, based on experience, these criteria
      were structured and implemented in the Relation Oriented Inference System (ROIS),
      in which information can be structured by defining relations. Illustrative black
      and white images were digitized and integrated into the shell. The performance of
      the resulting decision support system was evaluated by a group of six
      pathologists using a set of slides covering the spectrum of the most frequently
      occurring histological types of invasive breast cancer. The pathologists first
      assessed histological type according to standard morphological procedures. The
      cases were then reassessed with the decision support system available for
      consultation. The use of the decision support system appeared to influence the
      previously assessed histological type in about half of the cases. Using the
      decision support system, histological typing was more uniform and more in accord
      with a 'gold standard' set by two experts.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7821894
TI  - Perineurioma (storiform perineurial fibroma): clinico-pathological analysis of
      four cases.
AB  - Four cases of perineurioma (storiform perineurial fibroma) arising in the dermis,
      subcutis, or deep soft tissue have been studied. Two patients were female and two
      were male with ages ranging from 19 to 45 years. One lesion each arose on the
      chest wall, shoulder, neck, and elbow. Follow-up information in three patients
      revealed no recurrence. Histologically, the neoplasms were circumscribed but non
      encapsulated lesions and were composed of spindle cells with elongated bipolar
      cytoplasmic processes, inconspicuous fusiform nuclei and well-defined palely
      eosinophilic cytoplasm. These cells were arranged in whorls or lamellar-like
      structures and often demonstrated a storiform growth pattern. In areas, the
      tumour cells appeared larger with more rounded nuclei. Immunohistochemically,
      most of the tumour cells stained positive for epithelial membrane antigen and
      vimentin, but failed to stain for S-100 protein, neurofilament, desmoplakin, and
      CD34. Ultrastructurally, two cases showed fusiform tumour cells with long, thin
      cell processes separated by abundant collagen bundles. Tumour cells were covered
      by discontinuous external lamina, showed many pinocytic vesicles and occasionally
      desmosome-like structures. The morphology and EMA immunopositivity of
      perineurioma are similar to meningioma, especially to cutaneous meningioma type
      II. We believe that perineurioma and meningioma are closely related, but
      morphologically distinguishable, neoplasms.

PMID- 7821895
TI  - The extent of apoptosis in different types of high grade prostatic carcinoma.
AB  - Apoptosis is the genetically mediated mechanism by which individual cells are
      deleted from living tissues. The extent of apoptosis in human tumours has not
      been examined in detail. In this study, apoptotic indices were assessed
      semiquantitatively by light microscopy in routine haematoxylin and eosin (H & E)
      stained sections of 15 high-grade carcinomas of the prostate by light microscopy,
      using the 40 x objective, counting 2000-2500 tumour cells per case. The mean
      apoptotic index for nine solid undifferentiated carcinomas was 1.7% (range 0.2
      2.4%), for three small cell undifferentiated carcinomas 25.2% (range 10-37%), and
      for three secondary transitional cell carcinomas of the prostate 5.5% (range 2.4
      9.1%). In general, apoptosis was easily identified, using the 40 x objective.
      There were minor variations in apoptosis from field to field in each tumour, and
      greater variability in the apoptotic index was observed among the small cell
      undifferentiated carcinomas and transitional cell carcinomas. In conclusion,
      assessment of apoptosis in routine H & E sections of human tumours is feasible,
      but it remains to be determined whether the extent of apoptosis correlates with
      other determinants of biological behaviour.

PMID- 7821896
TI  - Nodular hyperplasia surrounding fibrolamellar carcinoma: a zone of arterialized
      liver parenchyma.
AB  - We report a case of acetaminophen-induced liver necrosis in a 14-year-old girl.
      At autopsy, a 9 cm subcapsular nodule was present in the right lobe of the liver
      which showed distinct zonation: a central greyish white area of fibrolamellar
      carcinoma with a peripheral fleshy, tan-coloured rim ranging from 1 to 2 cm in
      thickness. This peripheral zone consisted of nodular, hyperplastic parenchyma
      resembling the changes seen in focal nodular hyperplasia, and stood out from the
      adjacent necrotic parenchyma. The sparing of this zone from the deleterious
      effects of acetaminophen provides indirect evidence of a predominantly arterial
      rather than portal blood supply to this region. The arterial supply was most
      probably derived from the tumour vasculature and may explain the parenchymal
      hyperplasia sometimes reported adjacent to a fibrolamellar carcinoma. Awareness
      of this phenomenon is essential when evaluating a needle biopsy, as sampling of
      this region may lead to a false negative diagnosis.

PMID- 7821897
TI  - Dieulafoy's vascular malformation and primary pulmonary hypertension in a 10-year
      old girl.

PMID- 7821898
TI  - Multifocal mucinous neoplasia of the female genital system.

PMID- 7821899
TI  - Intravascular malignant lymphomatosis (angiotropic large-cell lymphoma). A case
      report with evidence for T-cell lineage with polymerase chain reaction analysis.

PMID- 7821900
TI  - Primary carcinoma of the prostate with diffuse oncocytic changes.

PMID- 7821901
TI  - Sclerosing thymoma--a possible phenomenon of regression.

PMID- 7821902
TI  - Primary lymphoma of the breast and lymphocytic lobulitis.

PMID- 7821903
TI  - Orange-red birefringence of gold particles.

PMID- 7821904
TI  - Hyaline globules in ovarian tumours.

PMID- 7821905
TI  - Cholestasis: a retrospective.

PMID- 7821906
TI  - Immunohistochemical detection of p53 protein as a prognostic indicator in
      prostate cancer.
AB  - Mutation of the p53 gene is the most common genetic alteration in human cancers.
      The mutant p53 protein is more stable than the wild type and can be detected by
      immunohistology. The objective of the current study was to evaluate the
      immunohistological detection of p53 protein in prostate cancer and its utility as
      a prognostic indicator. We used a monoclonal anti-p53 antibody and immunostained
      primary prostate adenocarcinomas (stages A1 to D1) from 109 patients with a mean
      follow-up of 3.8 years (range, 1.3 to 9.3 years). Immunoreactivity for p53 was
      seen in 23 cancers (21%). There were 12 instances of progression (14%) among the
      p53-negative cancers versus seven (30%) among the p53-positive group. Survival
      analysis using three univariate statistical tests showed that p53 reactivity (P <
      .03), Gleason score (P < .01), and stage (P < .05) had significant effects on
      time to progression of prostate cancer. Multivariate analyses showed that Gleason
      score was significant with all three tests; p53 reactivity was significant with
      the Wilcoxon test but only approached significance by the log rank and Cox tests.
      When the analyses included only patients with Gleason scores 2 to 7 (N = 94),
      univariate analyses showed that p53 reactivity was strongly related to
      progression of prostate cancer (P < .007). Stage also was significant (P < 0.04),
      but Gleason score was not. Multivariate analyses showed only p53 reactivity to be
      significant (P < .007). In conclusion, mutation of the p53 gene may be involved
      in prostate cancer carcinogenesis. p53 reactivity marks an aggressive subset of
      prostate cancer and appears to be an independent prognostic indicator that is
      particularly valuable among the low to intermediate grade cancers.

PMID- 7821907
TI  - Hantavirus pulmonary syndrome in the United States: a pathological description of
      a disease caused by a new agent.
AB  - An outbreak of an acute respiratory disease in the southwestern United States has
      led to the recognition of a new hantaviral illness. This report describes a
      unique spectrum of antemortem and postmortem pathological findings seen in a case
      series of nine surviving patients and 13 who died. Clinical, laboratory, and
      autopsy findings were derived from a consecutive series of individuals confirmed
      to have hantavirus pulmonary syndrome. Laboratory studies included chemical,
      hematological, and bone marrow analyses as well as flow cytometric and
      immunohistochemical phenotyping. Autopsy tissues were examined by routine
      histological stains, immunohistochemical methods, and transmission electron
      microscopy. The lung is the primary target organ in this illness. Pulmonary
      abnormalities include pleural effusions, alveolar edema and fibrin, and an
      interstitial mononuclear cell infiltrate. Large immunoblast type cells are seen
      in the lungs, blood, bone marrow, lymph nodes, liver, and spleen. A tetrad of
      hematological findings includes left-shifted neutrophilic leukocytosis,
      thrombocytopenia, hemoconcentration in severe cases, and circulating
      immunoblasts. In contrast to previously described nephropathic hantaviral
      syndromes, hantavirus pulmonary syndrome is characterized by a unique
      constellation of pulmonary, hematological, and reticuloendothelial pathological
      findings. The pulmonary findings are distinguishable from fatal adult respiratory
      distress syndrome. The data suggest a capillary leak syndrome restricted to the
      pulmonary circulation. Likewise, the hematological picture is unique and may be
      valuable in the rapid identification of cases for further diagnostic studies.

PMID- 7821908
TI  - Lethal arthrogryposis with anterior horn cell disease.
AB  - Fifteen infants (11 families) with lethal arthrogryposis and anterior horn motor
      neuron loss are described. The clinical presentation was the fetal akinesia
      deformation sequence (FADS) with multiple contractures and facial anomalies. At
      autopsy neurogenic muscular atrophy was present in all infants. The spinal cord
      showed a paucity of anterior horn motor neurons in the 12 infants studied. Both
      male and female infants were affected. Nine cases were sporadic, whereas in two
      families there were three affected cases. Consanguinity between the parents was
      reported in one family with one affected child. This and the recurrence of the
      condition speak for autosomal recessive inheritance. Detailed neuropathological
      examination and documentation of the clinical features are needed for a better
      delineation of and genetic counseling for perinatally lethal arthrogryposis.

PMID- 7821909
TI  - Giant cell myocarditis: monocytic immunophenotype of giant cells in a case
      associated with ulcerative colitis.
AB  - Giant cell myocarditis (GCM) is a rare condition whose histologic hallmark, the
      multinucleate giant cell, is of debated origin (monocytic v myogenic). We report
      the case of a 46-year-old woman with a previous diagnosis of ulcerative colitis
      who rapidly deteriorated and died as the result of refractory ventricular
      tachyarrhythmias. Postmortem examination showed a diffuse infiltration of the
      myocardium by round cells and multinucleate giant cells. Immunohistochemically,
      round cells were demonstrated to be T lymphocytes admixed with monocytes.
      Multinucleate giant cells expressed monocytic markers (MAC 387, lysozyme) and
      were negative for muscle markers (actin, desmin, myoglobin). This case
      illustrates the monocytic and macrophagic nature of multinucleate giant cells and
      lends support to the autoimmune hypothesis of GCM by the concurrence of the
      latter with ulcerative colitis.

PMID- 7821910
TI  - Adenosquamous carcinoma of the prostate.
AB  - We describe a patient with adenosquamous carcinoma of the prostate. His history
      suggests a common histogenesis of the glandular and squamous elements of the
      tumor. A 60-year-old white man had adenocarcinoma of the prostate diagnosed by
      biopsy and then underwent radical prostatectomy, which showed adenosquamous
      carcinoma. Immunoperoxidase in the glandular component was positive for prostate
      specific antigen (PSA), prostatic acid phosphatase (PAP), and low molecular
      weight keratin CAM 5.2 but was negative for high molecular weight keratin AE-3.
      The squamous component was negative for PSA, PAP, and CAM 5.2 but positive for AE
      3. Previously reported patients with adenosquamous carcinoma of the prostate
      share a history of radiation or hormonal therapy followed much later by
      prostatectomy, suggesting that adenosquamous carcinoma consists of residual
      primary adenocarcinoma and metaplastic squamous epithelium caused by radiation or
      hormonal treatment. However, the present case lacks this history, suggesting that
      the two types of epithelia may have developed concurrently.

PMID- 7821911
TI  - Pathological staging and prognostic indicators in rectal cancer.

PMID- 7821912
TI  - Tumors of pineal parenchymal cells: a correlation of histological features,
      including nucleolar organizer regions, with survival in 35 cases.
AB  - We studied 35 parenchymal neoplasms arising in the pineal gland, including 11
      pineoblastomas, 21 pineocytomas, and three mixed pineocytoma-pineoblastomas.
      Pineoblastomas were most commonly found in children (mean age, 12.6 years). The
      median postsurgical length of survival for seven patients, including five with
      remote metastases, with fatal outcome was 24 months. The 21 pineocytomas were
      found in older individuals (mean age, 26.8 years). Four patients with pineocytoma
      died; two before surgery and two in the immediate postoperative period. The
      remaining 17 patients survived for intervals between 6 and 118 months after
      surgery. Two mixed pineocytoma-pineoblastomas were found in infants who died a
      few months after biopsy, whereas a third patient, an adult, was alive at 46
      months after excision and irradiation. Both pineoblastoma and pineocytoma
      exhibited variable immunoreactivity to neurofilament proteins, synaptophysin,
      glial fibrillary acidic protein, S-100 protein, retinal-S antigen, and rhodopsin;
      the highest percentages of positive cells stained with synaptophysin. Three
      pineocytomas exhibited ganglionic differentiation and two of them also showed a
      glial component. Prognosis could not be correlated with the degree of divergent
      differentiation. Comparison of silver-stained nucleolar organizer region (AgNOR)
      counts between pineoblastomas and pineocytomas suggests that the former are more
      actively proliferative than the latter, with mixed pineocytoma-pineoblastoma
      showing intermediate activity. There was no correlation between AgNOR score and
      prognosis within the three tumor groups.

PMID- 7821913
TI  - Image cytometry determination of ploidy level, proliferative activity, and
      nuclear size in a series of 314 transitional bladder cell carcinomas.
AB  - Image cytometry was carried out on 281 superficial (Ta and T1) and 33 invasive
      (T2 to T4) bladder cancers. The parameters used to characterize these bladder
      tumors were: (1) histopathological grading, (2) clinical staging, (3) tumor size,
      (4) deoxyribonucleic acid (DNA) index (DI), (5) DNA histogram type (DHT), (6)
      percentage of euploid (diploid plus tetraploid) cells, (7) percentage of
      polyploid cells (> 5C DNA content), (8) proliferative activity (S phase fraction
      value), and (9) nuclear area (NA). The proliferative activity of the tumors was
      not related to either histopathological grade or to clinical stage, but it was
      related to the DHT parameter, which made it possible to identify diploid,
      hyperdiploid, triploid, hypertriploid, tetraploid, and polymorphic tumors. The
      hypertriploid tumors exhibited a significantly lower proliferative activity than
      the nonhypertriploid ones. Although both the DI and the NA values correlated
      significantly with histopathological grading, only the NA values correlated
      significantly with clinical staging. We further observed that some grade III
      bladder tumors were definitely diploid, whereas some grade I tumors were highly
      aneuploid. We thus hypothesize that the ploidy level of a given tumor reflects
      its age directly and its aggressiveness only very indirectly. In our opinion
      aneuploidy is only an indirect marker of aggressiveness because it reflects the
      fact that a malignant tumor is old, ie, has been present in a patient over a long
      period of time and has had ample time to express its malignancy at the clinical
      level. A significant relationship was accordingly obtained between tumor size and
      ploidy level with the highest proportion of aneuploid tumors and the highest
      percentage of polyploid cell nuclei being observed among the largest bladder
      tumors.

PMID- 7821914
TI  - Impact of the Crohn's-like lymphoid reaction on staging of right-sided colon
      cancer: results of multivariate analysis.
AB  - The presence of lymphoid aggregates within the muscularis propria or pericolic
      fibroadipose tissue apposing invasive colorectal carcinoma, termed the Crohn's
      like lymphoid reaction, has been related to improved patient length of survival
      according to univariate statistical analysis. We tested the Crohn's-like lymphoid
      reaction as an indicator of prognosis in a multivariate statistical analysis of
      344 resected right-sided colonic cancers. Improved 5-year survival in univariate
      analysis was associated with low tumor grade, regular tubule configuration,
      expanding tumor growth pattern, prominent peritumoral lymphocytic infiltration,
      absence of tumoral invasion of extramural veins, all levels of intramural and
      extramural invasion short of widespread local tumor permeation, conspicuous
      Crohn's-like lymphoid reaction, and absence of both nodal metastasis and nodal
      independent tumor nodules in pericolic fat. By the Cox proportional hazard model
      using the stepwise method, depth of tumor invasion, lymph node metastasis,
      Crohn's-like lymphoid reaction, and metastatic tumor nodules in pericolic fat
      retained independent prognostic significance. Combining the four variables to
      formulate pathological prognostic categories yielded a highly favorable
      prognostic group-92% 5-year survival and 95% confidence limits (88% to 96%)-
      encompassing 53% of the study population. It included all Dukes' stage A
      carcinomas, 66% of Dukes' stage B adenocarcinomas, and 11% of Dukes' stage C
      cancers. Lymph node metastases coupled with intramural and extramural extent of
      tumor invasion are the cornerstones of colorectal cancer staging. Addition of
      other variables improves prognostication for the cecum and ascending colon. From
      this study the Crohn's-like lymphoid reaction and metastatic tumor nodules in
      pericolic fat emerge as significant independent indicators of prognosis for right
      sided colon cancer. Complex correlations of both indicators with nonselected
      variables were observed.

PMID- 7821915
TI  - Splenic marginal zone cell lymphoma: report of an indolent variant without
      massive splenomegaly presumably representing an early phase of the disease.
AB  - Splenic marginal zone (MRZ) cell lymphoma is a recently described neoplasm
      arising in a unique compartment of splenic white pulp, producing massive
      splenomegaly and spreading to bone marrow and distant lymph nodes. We report
      three cases of splenic lymphoma that morphologically and immunohistochemically
      appear to originate from MRZ cells that presented as indolent neoplasms involving
      the spleen but with no or only moderate enlargement of the organ, presumably
      representing an early clinical stage of this disorder. Despite the evidence of
      involvement of the liver in one case, lymph nodes and bone marrow proved to be
      uninvolved. Histologically, the three spleens showed similar features, being
      characterized by the involvement of white pulp follicles and periarteriolar
      lymphoid sheaths by medium-sized lymphoid cells with slightly irregular nuclei
      and ample cytoplasm. Immunohistochemically, all the specimens expressed a series
      of B-lineage markers that, in contrast to specimens of monocytoid B cell lymphoma
      (MBCL) and hairy cell leukemia (HCL) studied for comparison, did not react with
      KiB3, LN1, and DBA.44 monoclonal antibodies.

PMID- 7821916
TI  - Mitotic frequency as a prognostic factor in breast cancer.
AB  - Grading of tumor malignancy in breast cancer should contribute essential
      information both for the prospective outcome of the individual patient as well as
      for TNM staging. In a series of 104 breast cancer patients we tested the
      prognostic validity and reproducibility of mitotic figure counting compared with
      TNM staging, Bloom and Richardson grading, DNA single cell cytometry, and
      morphometry. Four-micrometer thick hematoxylin-eosin-stained routine slides were
      investigated. Mitotic figures were counted in representative areas of the tumor
      in 10 159-microns 2-sized high power fields (HPFs) at a 400X magnification; the
      median value was seven and the threshold for the 25th percentile was three. This
      value should replace the common but prognostically invalid threshold of 10.
      Univariate survival analysis showed that mitotic figure counting allows the
      identification of three groups of patients (< or = 3, 4 to 20, > 20 mitoses per
      HPF) with significantly different survival probabilities (P < .0001; P = .0178).
      Depending on the number of mitotic figures, length of survival was significantly
      different within the group of T1N0 tumors (P = .0082) and the group of T1N1 or
      T2N0 tumors (P = .0251). In a Cox stepwise regression model mitotic frequency
      counting added prognostic information to tumor size and was of higher prognostic
      significance than lymph node status, DNA ploidy, or mean nuclear area. The 95%
      confidence limit for interobserver reproducibility, tested in 20 cases, was
      plus/minus 8 mitoses. After quartilization an agreement of 75% was observed.

PMID- 7821917
TI  - Differentiation potential of ovarian dysgerminoma: an immunohistochemical study
      of 15 cases.
AB  - An immunohistochemical study of 15 ovarian formalin-fixed, paraffin-embedded
      dysgerminomas showed positive staining of tumor cells for vimentin in all cases.
      Ten dysgerminomas stained for cytokeratin 18. Desmin positivity of single tumor
      cells was detected in four dysgerminomas. Glial fibrillary acidic protein was
      present in two tumors. Prominent human beta chorionic gonadotropin staining was
      seen in one tumor. S-100 protein was found in two and carcinoembryonic antigen in
      one of the dysgerminomas. Placental alkaline phosphatase was present in 12 of the
      15 tumors studied. The heterogeneity of the cytoskeletal profile and of other
      markers showed some similarities to our previously published results on
      testicular seminomas. Thus, in contrast to previous concepts, dysgerminoma, as is
      the case with its testicular counterpart the seminoma, appears to be capable of
      further differentiation, albeit at a primitive level. Our observations also may
      help to elucidate the relationship between dysgerminoma and other
      nondysgerminomatous ovarian germ cell tumors, and may be of help in the
      differential diagnosis with poorly differentiated carcinoma, ovarian lymphoma, or
      other germ cell tumors.

PMID- 7821918
TI  - Prognostic significance of an interface pattern of central fibrosis and tumor
      cells in peripheral adenocarcinoma of the lung.
AB  - Fifty-nine surgically resected pulmonary adenocarcinomas were histologically
      classified into four types (A, B, C, and D) according to the pattern of invasion,
      ie, the extent of invasive tumor cell growth in the interface zone between
      alveoli replaced by cancer cells and the central region of fibrosis (so-called
      "scar"). In pattern A cancer cells proliferate along the alveolar walls without
      forming a frankly invasive lesion. In pattern B invasive lesions occupy less than
      30% and in pattern C more than 30% of the fibrosing area. Pattern D refers to
      invasion of the bronchial lumen by cancer cells. The 59 tumors included 14 of
      pattern A, 12 of pattern B, 16 of pattern C, and 17 of pattern D. The 5-year
      survival rate for patients with pattern A tumors was 100%, and the rates for
      patients with pattern B, C, and D tumors were 64.2%, 30.0%, and 11.8%,
      respectively. Each difference between pairs of survival curves was statistically
      significant (P < .05). We found a correlation between the pattern of invasion and
      other prognostic factors. However, even in the cases evaluated as favorable by
      other prognostic factors (stage I, tumor less than 35 mm in diameter, negative
      for lymph node metastases, well-differentiated histology, negative for subpleural
      invasion, negative for vascular invasion) the survival curves became steeper
      going from pattern A to patterns B, C, and D. We conclude that the pattern of
      invasion is correlated with the prognosis of surgically treated patients. Our
      study may provide new histological criteria for the prognostic evaluation of
      pulmonary adenocarcinoma.

PMID- 7821919
TI  - Placentoid bullous lesion of the lung.
AB  - Four adult patients presented with unilateral multicystic lung disease. The cysts
      had been detected years previously on chest radiographs in three patients. Two
      patients had histories of repeated childhood pneumonias. Preoperative diagnosis
      of bullous emphysema with rupture was made in three patients who presented with
      pneumothorax. Lobectomy was done in two patients and pneumonectomy in two
      patients. Macroscopically, each lung was spongy with cysts that contained
      gelatinous vesicular or grape-like structures resembling normal or molar
      placental tissue. Bullous emphysema was evident in one lung and marked panacinar
      emphysema in another. In one patient who had a lobectomy, the ipsilateral lobe of
      compressed lung re-expanded after surgery and proved to be cystic as well on
      subsequent radiographs. The vesicular and grape-like structures
      histopathologically are papillary structures with central edematous cores and a
      covering of cuboidal epithelial cells. Degenerate villi became either
      hydatidiform, fibrotic, or calcified. At low magnification the histology was
      similar to that of placenta with hydatidiform change. Emphysematous lung in which
      villiform structures appeared at the edges of bullae was found histologically in
      two patients. Lymphangiectasia was present in all patients. The placentoid
      bullous lesion has distinct macroscopic and microscopic features and is
      clinically unusual in that the cysts are unilateral and appear in otherwise
      healthy young adults. We do not know whether the lesion is a malformation or a
      peculiar devolution of localized bullous emphysema. We favor the latter
      interpretation. Torsion of lung may cause the lymphangiectasia and contribute to
      the unusual histology. Excision is curative.

PMID- 7821920
TI  - Fetal thrombotic vasculopathy: the clinical significance of extensive avascular
      villi.
AB  - Thrombosis of large fetal vessels in the placenta leads to regions of downstream
      avascular villi (AV). Avascular villi have been associated with adverse outcomes
      in anecdotal reports, but no controlled study of their significance has been
      done. We prospectively gathered cases of extensive AV (n = 29) occurring over a 2
      year period at the Institute of Pathology at Case Western Reserve University and
      compared obstetric history, coexistent placental pathology, and neonatal outcome
      to gestational age-matched controls in a case control study. The diagnosis of
      extensive AV required one or more of the following characteristics: 2.5% or more
      of total villous parenchyma affected, foci in multiple sections, or a single
      lesion measuring 0.25 cm2 or larger. Women with AV placentas had increased rates
      of intrauterine growth retardation (IUGR), acute and chronic monitoring
      abnormalities, oligohydramnios, and maternal coagulation disorders. Placentas
      with AV were more likely to have coexistent chronic villitis, membrane
      hemosiderin, meconium in all three membrane layers, and villous chorangiosis.
      Finally, among the subgroup of neonates older than 34 weeks gestation without
      congenital malformations or coexistent placental pathology (n = 18), we
      identified significant abnormalities, including major thrombotic events (n = 5),
      neonatal death (n = 2), umbilical artery pH less than 7.10 (n = 4), platelet
      count less than 150,000 (n = 4), increased nucleated red blood cell (NRBC) counts
      (n = 7), and transient hypoglycemia (n = 4). Placental features correlating with
      clinical abnormalities included percentage of greater than 30% AV, recent
      platelet and fibrin aggregates, and multifocal disease involving more than one
      histological section.

PMID- 7821921
TI  - Expression of vascular permeability factor (vascular endothelial growth factor)
      and its receptors in breast cancer.
AB  - Solid tumors must induce a vascular stroma to grow beyond a minimal size, and the
      intensity of the angiogenic response has been correlated with prognosis in breast
      cancer patients. Vascular permeability factor (VPF), also known as vascular
      endothelial growth factor (VEGF), is a secreted protein that has been implicated
      in tumor-associated angiogenesis. Vascular permeability factor directly
      stimulates endothelial cell growth and also increases microvascular permeability,
      leading to the extravasation of plasma proteins, which alter the extracellular
      matrix in a manner that promotes angiogenesis. To determine whether VPF has a
      role in breast cancer, we used in situ hybridization to study VPF mRNA expression
      in normal breast tissue (13 specimens), comedo-type ductal carcinoma in situ
      (DCIS) (four specimens), infiltrating ductal carcinoma (12 specimens),
      infiltrating lobular carcinoma (two specimens), metastatic ductal carcinoma
      (three specimens) and metastatic lobular carcinoma (one specimen). Vascular
      permeability factor mRNA was expressed at a low level by normal duct epithelium
      but was expressed at high levels in tumor cells in all cases of comedo-type DCIS,
      infiltrating ductal carcinoma, and metastatic ductal carcinoma. In contrast, VPF
      mRNA was not expressed at high levels in infiltrating lobular carcinoma. We also
      used in situ hybridization to study the expression of two recently described
      endothelial cell surface VPF receptors, flt-1 and kdr. Vascular permeability
      factor receptor mRNA was strongly expressed in endothelial cells of small vessels
      adjacent to malignant tumor cells in DCIS, infiltrating ductal carcinoma, and
      metastatic ductal carcinoma. In contrast, no definite labeling for receptor mRNA
      was detected in infiltrating lobular carcinoma or nonmalignant breast tissue. The
      intense expression of VPF mRNA by breast carcinoma cells and of VPF receptor mRNA
      by endothelial cells of adjacent small blood vessels provides strong evidence
      linking VPF expression to the angiogenesis associated with comedo-type DCIS,
      infiltrating ductal, and metastatic ductal breast carcinoma.

PMID- 7821922
TI  - Biliary epithelial expression of pyruvate dehydrogenase complex in primary
      biliary cirrhosis: an immunohistochemical and immunoelectron microscopic study.
AB  - It has been reported recently that there is a unique distribution of the E2
      subunit of the pyruvate dehydrogenase complex (PDC-E2) on biliary epithelial
      cells in patients with primary biliary cirrhosis (PBC) but not primary sclerosing
      cholangitis. This distribution has been demonstrated using a mouse monoclonal
      antibody, coined C355.1. The epitope recognized by C355.1 is near the lipoic acid
      binding site of PDC-E2. C355.1 inhibits PDC-E2 activity in vitro and, unlike a
      panel of other monoclonal antibodies against different regions of PDC-E2, appears
      to bind not only to mitochondria but also to a unique antigen expressed
      predominantly on the luminal side of biliary epithelial cells in PBC. We have
      extended these observations by studying the subcellular reactivity of C355.1
      using postembedding immunoelectron microscopy on the intrahepatic small bile
      ducts of PBC livers, extrahepatic biliary obstruction (EBO) livers, and normal
      livers. We report that the reactivity of C355.1 can be classified into two
      categories. The first category is characterized by small foci of reaction
      products that were randomly dispersed in cytoplasm, particularly in supranuclear
      areas; the ultrastructural characterization of these foci was impossible to
      define but was similar in PBC and EBO. However, of particular interest was the
      second category of reactivity, which was characterized by deposition of reaction
      products around the biliary lumen, including microvilli and adjacent subluminal
      ectoplasm and secretory substances in the biliary lumen. This staining pattern
      was frequent in PBC livers, only occasionally evident in EBO livers, and not
      found in normal livers. These data further define and highlight the unique
      subcellular distribution of PDC-E2 around the biliary lumen in PBC livers and
      suggest that this abnormality is related to the pathogenesis of bile duct
      lesions.

PMID- 7821923
TI  - DNA ploidy status in 84 ocular melanomas: a study of DNA quantitation in ocular
      melanomas by flow cytometry and automatic and interactive static image analysis.
AB  - Deoxyribonucleic acid (DNA) ploidy was quantified in 84 ocular melanomas (median
      follow-up, 11-years) by flow cytometry, CAS 200 interactive image analysis, and
      Pathology Image Processing Environment (PIPE; Department of Quantitative
      Pathology, Free University, Amsterdam, The Netherlands) automatic image analysis
      (75). Overall, 32.1% of the melanomas were aneuploid, 2.3% were tetraploid, and
      66.6% were diploid. Pathology Image Processing Environment analysis estimated DNA
      ploidy in 12 tumors that were unprocessable by flow cytometry. Of 10 tumors that
      were diploid by flow cytometry, PIPE detected stemline aneuploidy in five and
      some aneuploid cells in five more. Seven tumors were aneuploid by PIPE but
      diploid by CAS 200, five of which contained occasional DNA aneuploid cells on the
      CAS 200 histograms. Pathology Image Processing Environment analysis quantified
      tumor samples with an average of 500 (250 to 1,050) cells in less than 10
      minutes. All cells classified as spindle A according to the Callender system
      (more than 10,000) were diploid. Spindle B and epithelioid cells occupied both
      diploid and aneuploid peaks on the DNA histograms. Dioxyribonucleic acid
      variables did not correlate with established prognosticators, such as Callender
      cell type, largest tumor dimension, or glaucoma, nor did they reach significance
      by univariate and multivariate analyses. The value of these findings as a
      diagnostic support in uveal melanoma, particularly in combination with fine
      needle aspiration biopsy, is discussed.

PMID- 7821924
TI  - Role of lymphoid organs in the pathogenesis of human immunodeficiency virus (HIV)
      infection.
AB  - The pathogenic mechanisms of HIV disease are multifactorial and multi-phasic. The
      common denominator of the disease is the profound immunosuppression that occurs
      in the vast majority of infected patients. Studies in lymphoid tissues in HIV
      disease have provided considerable insight into the pathogenic processes involved
      from the earliest phases of infection through the advanced stages. Following
      primary infection, virus is disseminated throughout the body and seeds the
      lymphoid tissue where its replication is only incompletely suppressed and where a
      reservoir of virus is established. Extracellular virus is trapped within the FDC
      of the lymph node germinal centers and serves as a source of infection for cells
      which reside in or migrate through the lymph node throughout the course of
      infection even during the early and often prolonged asymptomatic period.
      Eventually, the architecture of the lymphoid tissue is destroyed, compounding the
      immune dysfunction that results from the depletion of CD4+ T cells. In this
      regard, the lymphoid tissue of LTNPs is relatively intact and viral burden and
      replication is considerably lower in the peripheral blood and lymph node mono
      nuclear cells of LTNPs than in individuals whose disease progresses. Cytokines
      probably play a major role in the modulation of HIV expression in the milieu of
      the lymphoid tissue. Further understanding of the pathogenic mechanisms operative
      in the lymphoid tissues of HIV-infected individuals will have important
      implications in the design of therapeutic strategies involving both
      antiretroviral and immunomodulatory approaches.

PMID- 7821925
TI  - Antigenic variation of primate lentiviruses in humans and experimentally infected
      macaques.
AB  - Neutralizing antibodies in primate lentivirus infections closely parallel the
      pathogenic process. Fast progression to disease is concomitant with lack of
      neutralizing antibodies to autologous virus. Slow or no progression to disease is
      linked with production of neutralizing antibodies to autologous virus. Moreover,
      there is evidence from the monkey model that the extent to which neutralizing
      antibodies cross-react may also be linked with the pathogenic process.
      Accordingly, slow progression to disease is associated with the capacity to
      neutralize several isolates and, conversely, fast progressors neutralize single
      autologous isolates, if any at all. In humans, transmission of HIV-1 from mother
      to child occurs more frequently in absence of autologous and/or heterologous
      neutralizing antibodies to primary isolates. Thus there is evidence that virus
      neutralization-perhaps in concert with the biological properties of the virus-is
      an important factor in primate lentivirus pathogenesis and transmission. Open
      questions are i) the extent of heterologous neutralization in slow or
      nonprogressor HIV-1- and HIV-2-infected individuals, ii) role of neutralizing
      antibodies in sexual transmission, and iii) what governs the specificity, broad
      or narrow, of the neutralizing antibody response in different hosts. If we can
      answer these questions we may be able to design preventive measures against HIV
      infection and/or disease. Studies on the interaction of virus and immune system
      in the infected host may therefore not only teach us about the pathogenetic
      process, but also help in developing an HIV vaccine.

PMID- 7821926
TI  - The role of CD4 and its downmodulation in establishment and maintenance of HIV-1
      infection.

PMID- 7821927
TI  - Changing virus-host interactions in the course of HIV-1 infection.

PMID- 7821928
TI  - Cytokines from lymphoid organs of HIV-infected patients: production and role in
      the immune disequilibrium of the disease and in the development of B lymphomas.

PMID- 7821929
TI  - Role of TH1/TH2 cytokines in HIV infection.
AB  - Different experimental approaches were used to prove or disprove the "TH1/TH2
      switch theory" of HIV-infection. No increase, or even a decrease, in the
      production of TH2-type cytokines (IL-4, IL-5, and IL-10) by either bulk
      circulating mononuclear cells or CD4+ T-cell clones generated by PHA stimulation
      of single T cells from HIV-infected individuals in all stages of disease compared
      to HIV-negative donors was observed. However, enhanced proportions of CD4+ T-cell
      clones able to produce both TH1-type and TH2-type cytokines (TH0 clones) were
      derived from either skin-infiltrating, in vivo-activated, T cells or in vitro
      antigen-stimulated peripheral blood T cells of HIV-infected individuals. Of note,
      TH1, TH2 and TH0 clones obtained from HIV-seronegative healthy donors showed
      different ability to support viral replication after infection with HIV in vitro.
      All TH2 and most TH0 clones supported HIV replication efficiently, whereas TH1
      clones did not. These results suggest preferential HIV replication in T cells
      producing TH2-type cytokines rather than TH1/TH2 switch in HIV infection.

PMID- 7821930
TI  - Structural rearrangements in the transmembrane glycoprotein after receptor
      binding.

PMID- 7821931
TI  - Current trends in transcatheter treatment of cardiac arrhythmias.
AB  - Catheter ablation has become established as a gold standard therapy for patients
      suffering from many supraventricular and ventricular arrhythmias, offering a
      curative alternative to these patients by way of destroying or isolating the
      arrhythmia substrate. Radiofrequency has been used as a primary source of energy
      for transcatheter ablation due to its safety and efficacy. Another technique is
      transcoronary chemical ablation, consisting of the infusion of ethanol through
      the coronary blood supply to the site of origin of the arrhythmia. Most
      supraventricular arrhythmias like atrial tachycardia, atrioventricular nodal
      reentrant tachycardia and arrhythmias related to atrioventricular accessory
      pathways can be managed with radiofrequency catheter ablation. However, some
      concerns exist regarding the value of this technique for the treatment of atrial
      flutter and ventricular tachycardia. In this review we discuss the state-of-the
      art in catheter ablation of cardiac arrhythmias and its future perspectives.

PMID- 7821932
TI  - Atrial contribution to left ventricular filling in mitral stenosis: effects of
      balloon mitral valvuloplasty.
AB  - Doppler echocardiographic contribution of atrial systole to left ventricular
      filling (AC) was studied in 20 patients with mitral stenosis and compared with
      that obtained from 15 matched controls in a prospective study. AC in mitral
      stenosis as a percentage of total filling volume was 8 +/- 2.8% compared to 12.5
      +/- 3.3% in control subjects (p < 0.001) and was weakly correlated to diastolic
      filling period (r = -0.45), mitral valve orifice resistance (r = -0.36) and heart
      rate (r = 0.36). An increase in mitral valve orifice area following balloon
      mitral valvuloplasty (0.78 +/- 0.12 to 1.72 +/- 0.4 cm2, p < 0.0001) resulted in
      an increase in AC to near normal values (8 +/- 2.8% to 12.5 +/- 3.8%, p < 0.001)
      coupled with an increase in cardiac index and a significant decrease in diastolic
      filling period and left atrial size. In conclusion, AC in young patients with
      severe mitral stenosis is decreased proportionately less than that reported in
      the older patients, is weakly correlated to mitral orifice resistance and
      normalises following a successful mitral valvuloplasty.

PMID- 7821933
TI  - Multiplane transesophageal echocardiography: our initial experience.
AB  - We present our experience in the diagnostic assessment of a wide spectrum of
      cardiovascular disorders using multiplane transesophageal echocardiography (MP
      TEE). Two hundred and seventeen patients in the age range of 11-71 years were
      subjected to MP-TEE from January to November 1993. The male:female ratio was
      1.1:1. One hundred and ten patients had predominantly mitral valve disease of
      rheumatic origin, eleven had mitral valve prolapse, twenty patients had aortic
      valve disease and thirty seven patients had more than one valve involvement. Six
      patients with suspected prosthetic heart valve dysfunction and ten patients of
      hypertrophic cardiomyopathy were also studied. Two patients had unexplained
      pulmonary hypertension, three had pericardial disease and three had proximal
      aortic dissections. Twenty six patients with congenital heart disease were
      studied of which nineteen had atrial septal defects, one had corrected
      transposition of great vessels with pulmonic stenosis and one adult had Ebstein's
      anomaly of the tricuspid valve. In our experience, MP-TEE enhances the
      versatility of TEE by providing incremental diagnostic information and enhancing
      delineation of pathology. The procedure was well-tolerated and no complications
      occurred.

PMID- 7821934
TI  - Comparative clinical and electrophysiologic effects of adenosine and verapamil on
      termination of paroxysmal supraventricular tachycardia.
AB  - The efficacy and electrophysiologic effects of adenosine and verapamil in
      termination of paroxysmal supraventricular tachycardia (SVT) were compared in 18
      patients (age 18-48 years, mean 33 +/- 9 years) with recurrent sustained and
      inducible SVT. Ten patients had atrioventricular nodal reentrant tachycardia
      (AVNRT) and 8 had atrioventricular reentrant tachycardia involving a retrograde
      accessory pathway (cycle length of SVT 280-360 msec; mean 315 +/- 20 msec). Each
      patient served as his own control. After induction of SVT, adenosine was
      administered first (6 mg i.v. bolus). If the tachycardia was not terminated, a
      bolus of 12 mg was given. Ten minutes later, verapamil (5 mg i.v. over 30 sec)
      was administered after reinduction of SVT. If the tachycardia was not terminated,
      a 5 mg dose was repeated every 5 minutes upto 20 mg. Adenosine terminated the SVT
      in 16 cases (6 mg - 7 patients, 12 mg - 9 patients). Verapamil was effective in
      11 patients (5 mg - 6 patients, 10 mg - 4 patients, 15 mg - 1 patient, 20 mg -
      nil). The overall efficacy of adenosine (89%) was significantly greater than that
      of verapamil (61%; p < 0.05). Adenosine terminated the tachycardia more quickly
      than verapamil (mean 24 +/- 11 sec versus 142 +/- 40 sec; p < 0.01). Termination
      of tachycardia by both drugs was related to antegrade block of the
      atrioventricular node in all patients except one with AVNRT in whom adenosine
      blocked the retrograde fast pathway. Ventricular premature beats were seen
      transiently in 5 patients following adenosine. Transient side effects such as
      flushing, burning and chest pain were frequently observed with adenosine and
      correlated with the termination of tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7821935
TI  - Influence of alcohol intake on high density lipoprotein cholesterol levels in
      middle-aged men.
AB  - To study the influence of alcohol (ethanol) intake on high density lipoprotein
      cholesterol (HDLC) levels, we studied 210 healthy middle-aged men (age 45 +/- 8
      years). Other factors influencing HDLC (physical exercise, diet, smoking and body
      mass index) were also studied. Individuals were classified according to daily
      ethanol consumption. There were 39 teetotallers, 29 took drink, 30 took 1-1.9, 25
      took 2-2.9, 26 took 3-3.9, 28 took 4-4.9 and 33 took 5 or more drinks per day (1
      drink = 14 gm ethanol). The overall mean serum total cholesterol was 191.4 +/- 53
      mg/dl and HDLC was 46.4 +/- 9 mg/dl. Total cholesterol in teetotallers was not
      different from those consuming different amounts of alcohol. HDLC in teetotallers
      (44.5 +/- 8 mg/dl) was significantly lower than in those taking 1-1.9 drinks
      (46.7 +/- 11 mg/dl, p < 0.05) and 2-2.9 drinks/day (51.4 +/- 9 mg/dl, p < 0.01)
      but was not different from those consuming > or = 3.0 drinks. There was a weak
      positive linear correlation between ethanol and HDLC (r = 0.016). HDLC levels
      were significantly lower in smokers (43.5 +/- 9 vs 47.2 +/- 11 mg/dl in non
      smokers), in non-vegetarians (43.5 +/- 10 vs 46.2 +/- 9 mg/dl in vegetarians) and
      in those with sedentary habits (42.4 +/- 7 vs 46.1 +/- 10 mg/dl in physically
      active). Low level ethanol consumption (< 3 drinks or 42 gm per day) is
      associated with increased HDLC levels.

PMID- 7821936
TI  - A follow up study of major intimal dissections treated with perfusion balloon
      catheter.
AB  - Major intimal dissections during coronary angioplasty are an important cause of
      early morbidity and mortality. In the recent past various non-surgical modalities
      to manage such dissections have been developed. The choice of therapy among these
      needs knowledge not only of immediate success but also of long term results. Data
      on long term follow up of patients managed with prolonged balloon inflations
      using a perfusion balloon catheter is limited. We herein report our experience of
      twenty seven consecutive patients managed by prolonged dilatations using Stack
      perfusion balloon catheter. All the patients had a long dissection with luminal
      compromise, 6 (22%) had in addition an acute complete occlusion, and in 4 (15%)
      there was a thrombus. Only 6 (22%) needed an emergency CABG, with the remaining
      having an event free hospital stay. At follow up after 6-26 months, 7/21 (33%)
      had severe symptoms and 5 of them underwent coronary arteriography with four
      having a repeat successful dilatation. The findings of this study suggest that
      the perfusion balloon catheter is a useful modality for management of major
      dissections with a restenosis rate similar to that of primary PTCA. Randomised
      controlled trials are required to assess its efficacy vis a vis the newer
      therapeutic options like stents, lasers and atherectomy.

PMID- 7821937
TI  - Study of platelet ultrastructure in ischemic heart disease.
AB  - The present work was undertaken to study the ultrastructural morphology of blood
      platelets in angiographically proven patients of ischemic heart disease by
      scanning and transmission electron microscopy. Various morphological forms of
      platelets viz. discoid, pseudotubular, membranous, saccular, pseudopodical and
      hyaline were observed. They showed varying degrees of alterations in organelles
      and membrane systems. These morphological changes prove that platelets are in an
      activated state in ischemic heart disease, explaining the functional alterations
      that have been extensively studied in previous reports.

PMID- 7821938
TI  - Congenital left ventricular inflow obstructions--an echocardiographic study.
AB  - Thirty nine consecutive cases of congenital left ventricular inflow obstructions
      (LVIO) diagnosed by two dimensional and Doppler echocardiography are described.
      The commonest referral diagnosis was severe pulmonary arterial hypertension.
      Confirmation by cardiac catheterisation and/or surgery was available in twenty
      one of these cases. The ages ranged from one month to 15 years (mean 3.8 +/- 4.5
      years) and 28 were males. Four types of LVIO were defined: i) Congenital mitral
      stenosis (22 cases). Ventricular septal defect was the commonest association. ii)
      Cor-triatriatum (7 cases) Out of three patients operated, in one it was found to
      be a supravalvular mitral ring and not cor-triatriatum as earlier thought on
      echocardiography. iii) Pulmonary venous obstruction (8 cases). Atrial septal
      defect and ventricular septal defect were the common associations. iv)
      Supravalvular mitral ring (2 cases). Double outlet right ventricle and a large
      ventricular septal defect were associated with one case each. In our experience,
      two dimensional and Doppler echocardiography is a very useful and reliable
      investigation for defining the various types of congenital left ventricular
      inflow obstructions and their hemodynamic significance.

PMID- 7821939
TI  - Primary pulmonary hypertension: natural history and prognostic factors.
AB  - A retrospective cohort study was carried out in 61 patients (30 males, 31
      females, age 24.6 +/- 11.8 years) with primary pulmonary hypertension diagnosed
      by strict clinical and hemodynamic criteria, to obtain an understanding of the
      natural history and prognostic markers. While 15 patients were alive, 46 patients
      (76%) had expired during the follow up period. Two, five and ten years survivals
      were 48%, 32% and 12% respectively. Median survival duration from time of
      diagnosis was 22 months. The survivors had significantly higher age of onset,
      cardiac index and significantly lower right atrial mean pressure, right
      ventricular end diastolic pressure, cardiothoracic ratio from chest rontgenogram
      and calculated pulmonary vascular resistance as compared to non survivors. While
      pulmonary artery systolic pressure was not significantly different, pulmonary
      artery diastolic and pulmonary artery mean pressures were significantly lower in
      survivors than in non-survivors. Lower New York Heart Association class, right
      atrial mean pressure < or = 7 mm Hg, right ventricular end diastolic pressure <
      or = 10 mmHg, cardiac index > 2.5 L/min/m2, pulmonary arterial oxygen saturation
      > 60%, were associated with significantly longer survival. The degree of
      pulmonary arterial hypertension had an indirect prognostic effect through the
      above parameters. Vasodilator therapy did not significantly alter the outcome of
      patients with primary pulmonary hypertension.

PMID- 7821940
TI  - Carotid artery occlusion causes reversible brain damage in rat.
AB  - In order to assess the density and distribution of brain damage after pure focal
      ischemia uncomplicated by hypotension or hypoxia, ischemia was produced by
      occlusion of one and/or both common carotid arteries (CCA) temporarily or
      permanently in the rat, followed by 3 months recovery. The brains were perfusion
      fixed with formaldehyde, embedded in paraffin, subserially sectioned, and stained
      with hematoxylin-eosin/cresyl violet. Mild ipsilateral neuronal damage was
      observed after unilateral permanent occlusion, but confined only to the
      hippocampus. Damage of neocortical neurons began to appear after 1 day following
      bilateral permanent occlusion. Damage was worst over the superolateral convexity
      of both hemispheres, CA 4 and subiculur neurons; subsequently other sectors of
      hippocampus and other brain structures were affected. Some damaged neurons in the
      superficial cortex and CA 1 sector of hippocampus, and almost all in the other
      regions of brain reverted to normal profile by 3 months of recovery. All brain
      structures showed normal profiles, except a relative neuronal rarefication in
      neocortex and CA 1 sector of hippocampus after 3 months of recovery. These
      results suggests that only CCA occlusion causes partial/incomplete ischemia in
      the rat brain, where damaging effects are counterbalanced by metabolic and
      circulatory adjustments.

PMID- 7821941
TI  - Right to left shunting in atrial septal defect due to isolated right ventricular
      hypoplasia.

PMID- 7821942
TI  - Torsade de pointes complicating treatment with astemizol.

PMID- 7821943
TI  - Occurrence of torsade de pointes with use of astemizole.

PMID- 7821944
TI  - Twiddler's syndrome--a remedy.

PMID- 7821945
TI  - [Campylobacter fetus subsp. fetus in a patient with liver cirrhosis].

PMID- 7821946
TI  - [Diagnosis and therapy of chronic viral hepatitis].

PMID- 7821948
TI  - [Sepsis--septicemia--sepsis syndrome].

PMID- 7821947
TI  - [Wellcome research stipends for clinical virology 1994].

PMID- 7821949
TI  - [Microbiological diagnosis of sepsis].
AB  - The detection of microorganisms responsible for septicemia from blood and their
      susceptibility testing against antimicrobial agents is the main requirement to
      treat this life threatening infection. The sample of specimens, their transport
      and the handling of blood cultures in the microbiological laboratory are really
      important, e.g. the number of blood cultures needed, the proper interval between
      these cultures, the volume of blood cultures and the use of sterile techniques.
      Recommendations are given for this important management. Conventional methods for
      blood cultures as well as new automatically working techniques are described.

PMID- 7821950
TI  - [Immune mechanisms of post-traumatic hyperinflammation and sepsis].
AB  - Major trauma and consecutively associated infectious complications have a major
      impact on the mechanisms of the specific immune response and the nonspecific
      inflammatory reaction. The trauma-induced host defense abnormalities become
      strikingly evident with the analysis of cytokine synthesis patterns. The
      dissociation of cell-mediated immune responses following trauma is based upon an
      overrepresentation of suppressor-active monocytes and inadequate T-cell help in
      parallel. Corresponding dysregulation of cytokine production appears within many
      facets. Complement, endotoxin and antigen antibody complexes cause a massive
      activation of monocytes with an abnormal release of essential mediators, like
      PGE2, IL-1, IL-6, IL-8, TGF-beta and TNF-alpha. The regulation of cytokine
      synthesis under stressful conditions is differentially regulated for the
      individual mediators, either on a transcriptional or a posttranscriptional level.
      In our opinion, the endogenous provisions of the organism for survival following
      major injury are inadequate and from this hypothesis we derive the necessity for
      a substantial exogenous therapeutic intervention. The primary target of modern
      immunotherapy must be to inhibit the conversion of a systemic inflammatory
      reaction in immunocompromised patients towards a status of bacterial sepsis.
      Different approaches appear to be feasible to avoid the development of late
      multiorgan failure. These interventions have to be utilized preventively in a
      controlled manner as early as possible after trauma has occurred, and they must
      effectively protect different cell systems (lymphocytes, monocytes, PMNs and
      endothelial cells).

PMID- 7821951
TI  - [Fingerprinting with the polymerase chain reaction: confirmation of a
      Enterobacter cloacae epidemic in a neonatal intensive care unit].
AB  - Between end December 1993 and end January 1994 a cluster of children
      infected/colonized with Enterobacter cloacae was seen in the neonatal intensive
      care unit of the University Hospital Nijmegen. The results of the epidemiological
      investigation are reported, which was aimed to differentiate between a random
      cluster of endogenously acquired Enterobacter strains and those possibly acquired
      exogenously via cross-infection. 5 isolates of the 7 patients were available for
      fingerprinting using interrepeat PCR. According to the fingerprint pattern, 4 of
      these isolates were identical, thereby suggesting cross-infection among the
      children. 3 neonates were colonized/infected with genotypically different
      isolates, suggesting that the infection/colonization developed endogenously. A
      control strain isolated from a patient at another ward showed the same genotype
      as the outbreak isolates. The transmission took probably place through one of the
      surgeons who, among all possible health care workers, were the only professional
      group treating patients in both units.

PMID- 7821952
TI  - [Comparison of serological tests for Chlamydia with particular emphasis on
      anticellular antibodies].
AB  - The influence of anticellular antibodies on reading and interpretation of
      Chlamydia-specific antibodies was investigated with selected sera in three
      commercial tests before and after absorption with noninfected cells. In two tests
      using C.trachomatis-L2-infected BGM- and L 929 cells, respectively, several sera
      could not be evaluated by unspecific reactions. The test system using only
      elementary bodies of C.trachomatis L2 showed no unspecific reactions.

PMID- 7821953
TI  - [Comparison of granulocyte function in diabetes mellitus type 1 and type 2].
AB  - The phagocytosis rate of polymorphonuclear leucocytes was measured by flow
      cytometry. Vital bacteria were incubated in whole blood. 111 blood samples were
      measured, 54 in diabetic patients (14 type 1 and 40 type 2), the rest of 57
      samples in healthy controls. Results showed firstly, that a decompensation in
      glucose metabolism in diabetic patients correlated with a decrease in
      phagocytosis. The HbA1 level was more closely correlated than the glucose level.
      The second result was, that despite a similar grade of decompensation in type 1
      and type 2 diabetic patients, the phagocytosis was significantly lower in type 1
      diabetes. No correlation was found concerning age and sex. These findings show,
      that the impact on granulocytic function in diabetes is of multifactorial origin,
      not only a shorter or longer elevation of the serum glucose level can explain it
      solely.

PMID- 7821954
TI  - Anti-class II MHC antibodies prevent and treat EAE without APC depletion.
AB  - We have demonstrated that a murine IgG1 anti-class II major histocompatibility
      complex (MHC) antibody (OX6) is able both to prevent and treat experimental
      autoimmune encephalomyelitis (EAE) in the Biozzi AB/H mouse. We have confirmed
      that this antibody is poorly cytotoxic, allowing mechanisms of action other than
      depletion of antigen-presenting cells (APC) to be assessed. Despite its effect on
      disease, OX6 administration does not prevent priming of T cells in the draining
      lymph node, implying an alternative mechanism for regulation of the autoimmune
      disease process.

PMID- 7821955
TI  - Human monoclonal rheumatoid factors: incidence of cross-reactions with tissue
      components and correlation with VH gene usage.
AB  - Human monoclonal antibodies with rheumatoid factor (RF) activity, derived from
      lymphocytes from the synovial tissue of rheumatoid arthritis (RA) patients and
      the peripheral blood of healthy individuals were examined for cross-reactivity
      with tissue and cellular antigens. The majority of IgM RF from RA patients (68%)
      showed reactivity with at least one component, and were frequently multispecific.
      A very significantly smaller proportion (28%) of the RF derived from healthy
      individuals demonstrated reactivities against tissue/cellular antigens (P =
      0.004). RF from RA patients most commonly reacted with gastric glands (61%),
      nuclei (50%) and smooth muscle (50%), whereas RF from healthy donors most
      commonly reacted with gastric glands (20%), smooth muscle (16%), endothelium
      (16%) and glomeruli (16%). The most striking difference between the two groups
      was the reactivity with nuclear components, demonstrated by 50% of the RA RF, but
      by none of the healthy donor RF. As the two groups of antibodies share the same
      specificity for IgG Fc, but show differences in variable region segment usage, we
      investigated the relationship between VH gene usage and tissue/cell cross
      reactivity using these antibodies and anti-blood group antibodies. Antibodies
      using VH3 or VH4 gene segments showed a very significantly greater frequency of
      tissue/cell reactions than those using VH1 (P = 0.0095 and 0.0004 respectively).

PMID- 7821956
TI  - Discrimination between alternatively spliced STP-A and -B isoforms of CD46.
AB  - CD46 (membrane cofactor protein; MCP) is ubiquitously expressed on nucleated
      human cells; it has a protective function, binding C3b and C4b, which are then
      cleaved by serum factor I. CD46 molecules (55,000-65,000 MW) have four short
      consensus repeats (SCR): the function of SCR-1 and -2 is unknown; SCR-3 and -4
      bind C3b and C4b. These are succeeded by the STP region, which can contain three
      separate regions (STP-A, -B, -C) rich in serine, threonine and proline and which
      are heavily glycosylated, succeeded by transmembrane and cytoplasmic tail regions
      (of which there are several). Multiple isoforms exist due to the different
      splicing of exons: STP-A and -B can thus be present or absent. So far these
      products can only be detected separately by polymerase chain reaction (PCR) and
      RNA studies; we now describe their detection by anti-peptide antibodies. Peptides
      whose sequences corresponded with those of STP-A and STP-B were synthesized and
      used for the immunization of mice; although they differ in only seven of 21 amino
      acids, monoclonal antibodies (mAb) that reacted specifically with STP-A but not
      with STP-B, and mAb that reacted specifically with STP-B but not with STP-A, were
      produced; these reacted specifically with native CD46 on human tissues and cell
      lines. STP-A mAb reacted with tissues in which STP-A RNA had been found, some
      leukaemias and cell lines; in normal tissue expression was mainly found in the
      intestine (large and small) and salivary gland. Anti-STP-B reacted with most
      tissues and cell lines. The antibodies should be of use in defining the
      expression and function of CD46 in different tissues.

PMID- 7821957
TI  - Dendritic cells of the oral mucosa and the induction of oral tolerance. A local
      affair.
AB  - The oral mucosa is an important site to induce immunological tolerance to protein
      antigens. Previously we have established that oral contacts to allergen can lead
      to systemic tolerance in both humans and experimental animals. Because of the
      importance of tolerance induction as a possible way to modulate allergic
      reactivity, we wished to study the mechanisms involved in efficient tolerance
      induction via the oral mucosa. Dendritic Langerhans' cells in both skin and oral
      epithelium are the first cells to encounter antigen. Therefore, possible
      functional differences between Langerhans' cells from skin and oral mucosa were
      studied by migration and transfer experiments. It was found that dendritic cells
      derived from the oral mucosa were not able to transfer tolerance, but that they
      acted as antigen-presenting cells in sensu stricto irrespective of the source and
      route of antigen administration.

PMID- 7821958
TI  - Pulmonary surfactant inhibits monocyte bactericidal functions by altering
      activation of protein kinase A and C.
AB  - Pulmonary surfactant, the main function of which is to reduce surface tension in
      the alveoli, is also known to affect the functions of monocytes. Two protein
      kinases play a role in the regulation of the bactericidal functions of
      phagocytes, i.e. cAMP-dependent protein kinase A (PKA), which is involved in
      inhibition, and Ca2+/phospholipid-dependent PKC, which is involved in stimulation
      of these functions. In the present study we investigated whether altered
      activation of PKA and/or PKC plays a role in the surfactant-induced inhibition of
      both the intracellular killing of Staphylococcus aureus and the production of
      reactive oxygen intermediates (ROI) by monocytes. The significance of increased
      activation of PKA was demonstrated by the following findings. Firstly, surfactant
      induced a sustained increase in the intracellular cAMP concentration in
      monocytes. Secondly, dibutyryl-cAMP (db-cAMP), a membrane-permeable cAMP
      analogue, mimicked the inhibitory effects of surfactant on both the killing
      capacity and the production of ROI by monocytes. Thirdly, an inhibitor of PKA
      partially restored the impaired bactericidal functions of monocytes incubated
      with surfactant. The involvement of decreased activation of PKC in the impaired
      bactericidal functions of monocytes incubated with surfactant was evident from
      two findings. Firstly, surfactant attenuated the phorbol myristate acetate (PMA)
      mediated translocation of PKC. Secondly, surfactant inhibited the production of
      O2- by monocytes upon stimulation with PMA. Therefore, the mechanism involved in
      the surfactant-induced inhibition of the bactericidal functions of monocytes
      comprises both activation of an inhibitory pathway, which includes cAMP and PKA,
      and inactivation of a stimulatory pathway, in which PKC is involved.

PMID- 7821959
TI  - Rat macrophage lysosomal membrane antigen recognized by monoclonal antibody ED1.
AB  - The monoclonal antibody (mAb) ED1 is being used widely as a marker for rat
      macrophages. The distribution of the recognized antigen in tissues and isolated
      cells strongly supports this use as a macrophage marker, since the majority of
      macrophages are recognized and only seldomly are other cell types stained by mAb
      ED1. In the present study we further characterized the recognized antigen by a
      detailed description of the localization of the antigen and by determining
      biochemical and functional properties. We show that the antigen is expressed on
      the membranes of cytoplasmic granules, like phagolysosomes, as well as on the
      cell surface. The amount of ED1 expression in a single cell can be correlated to
      phagocytic activity of the respective cell type, but the mAb ED1 is not able to
      block latex phagocytosis or bacterial killing. The mAb ED1 appears to recognize a
      heavily glycosylated protein of 90,000-110,000 MW, depending on the cell type
      used as antigen source. A possible relation with other known lysosomal
      glycoproteins with a similar molecular weight is discussed.

PMID- 7821960
TI  - The type of interaction with Fc gamma R in human monocytes determines the
      efficiency of the generation of oxidative burst.
AB  - Receptors for the Fc fragment of IgG (Fc gamma R) have a well-documented role in
      the generation of oxidative burst. It is tempting to speculate that the type of
      interaction with Fc gamma R could be a mechanism of regulation of this process.
      Here we report on a comparative study of the induction of oxidative burst in
      human monocytes activated by means of different types of interaction with Fc
      gamma R. We studied non-primed monocytes obtained by centrifugal elutriation from
      healthy donors. These cells were submitted to Fc gamma R interactions following
      two distinct models: one, using particulate material (IgG-SRBC leading to
      phagocytosis or rosetting), and another using soluble reagents followed by cross
      linking of the receptors (monoclonal antibodies against Fc gamma RI and Fc gamma
      RII and natural ligands, namely several isotypes of murine and human IgG).
      Phagocytosis and oxidative burst were studied simultaneously in the monocytes,
      following the methodology described recently. Human non-primed monocytes were
      able to generate a very obvious oxidative burst response after activation of Fc
      gamma R by particulate material. The same response was observed when Fc gamma RII
      was blocked by monoclonal antibodies. Ingestion was not necessary for activation
      of the oxidative burst, since the model of rosetting induced a level of burst
      generation similar to the one obtained in the phagocytic process. Cross-linking
      of Fc gamma RI by soluble reagents induced production of reactive oxidative
      intermediates (ROI) only when the ligand-binding site of the receptor was
      involved. These data lead to the conclusion that Fc gamma R interaction with
      soluble or particulate material induces oxidative burst in non-primed human
      monocytes only when the binding site of natural ligands is involved. The type of
      interaction also determines the efficiency of the generation of ROI. This fact
      could represent a regulatory mechanism.

PMID- 7821961
TI  - Concomitant in vivo production of 19 different cytokines in human tonsils.
AB  - Accumulating data indicate that cytokines, peptides involved in regulation of
      both physiological and pathological immune responses, are produced predominantly
      at the site of local antigen stimulation. Cytokine-producing cells were detected
      at the protein level in human tonsil tissue obtained from children with recurrent
      tonsillitis or infectious mononucleosis (IM). Concomitant production of 19
      different human cytokines, interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-1
      receptor antagonist (ra), IL-2, IL-3, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13,
      granulocyte-macrophage colony-stimulating factor (GM-CSF), G-CSF, tumour necrosis
      factor-alpha (TNF-alpha), TNF-beta, interferon-gamma (IFN-gamma) and transforming
      growth factor-beta 1-3 (TGF-beta 1-3), was identified at a single-cell level by
      indirect immunohistochemical staining procedures and use of carefully selected
      cytokine-specific antibodies (Ab). Fresh frozen sections were fixed with 4%
      paraformaldehyde and permeabilized by 0.1% saponin treatment, eluting cholesterol
      from the cell-surface membrane and the Golgi complex. The intracellular
      localization of all cytokines, except IL-1 and IL-1ra, was demonstrated by a
      characteristic local cytoplasmic perinuclear configuration in producer cells. In
      addition, the immunoreactivity for certain cytokines (IL-2, IL-4, IL-5, G-CSF and
      GM-CSF) was expressed on the cell membranes and extended over a large
      extracellular area encompassing the producer cell. Localization of the cytokine
      to the Golgi organelle was established by co-staining with a monoclonal antibody
      (mAb) specific to the Golgi complex. Both the extra- and intracellular cytokine
      staining reactions could be blocked by preincubation of the cytokine-specific Ab
      with the corresponding purified natural or recombinant cytokine. A complex
      cytokine pattern was established in both groups studied, where most T-helper type
      1 (Th1) and Th2 lymphokines were expressed in the tonsils but at different
      frequencies and localizations. Cells expressing IL-4, IL-5, IL-10 and IL-13, (Th2
      response) were evident at higher frequencies in recurrent tonsillitis compared to
      sections from IM, which were associated with a more pronounced IL-2, IFN-gamma
      and TNF-beta expression.

PMID- 7821962
TI  - Limiting dilution analysis reveals the precursors of interleukin-4-producing CD4+
      cells induced by protein immunization.
AB  - Although cytokine-producing T cells play a key role in the response to
      vaccination, they are not always revealed by antigen stimulation of primed
      lymphoid cells in vitro. In this study, mice were immunized subcutaneously with
      alum-precipitated keyhole limpet haemocyanin (KLH) in adjuvant to activate
      interleukin-4 (IL-4)-producing CD4+ T cells. IL-4 mRNA was the dominant cytokine
      mRNA species found in draining lymph nodes (LN) 7 days after immunization and its
      levels were increased after in vitro stimulation with KLH for 24 hr. IL-4
      protein, on the other hand, was not detected in the supernatants of such antigen
      stimulated cultures. The presence of T cells primed for IL-4 production was
      nevertheless suggested by the findings that primed LN cells produced low IL-4
      titres in response to anti-CD3 antibody, whereas normal LN cells did not, and
      primed CD4+ LN cells produced readily detectable IL-4 levels in response to
      antigen after one or more cycles of in vitro restimulation. Culture at limiting
      dilution showed that 1-2% of 7 day KLH-primed CD4+ LN cells were clonogenic and
      specific for KLH without prior expansion in vitro, and that this frequency was
      markedly increased by repeated stimulation in bulk culture. Most clonogenic cells
      in primed LN gave rise to IL-4-secreting clones and a smaller number gave rise to
      interferon-gamma (IFN-gamma)-producing clones. The precursor frequency of IL-4
      producing CD4+ cells in primed LN and the average IL-4 titre per cloned cell
      support the conclusion that these two parameters account for the low levels of IL
      4 produced in bulk culture by LN cells from immunized mice.

PMID- 7821963
TI  - Enhancement of human lymphocyte proliferative response to purified protein
      derivative by an anti-interleukin-2 receptor alpha chain antibody (CD25).
AB  - While it is clear that the beta subunit of interleukin-2 receptor (IL-2R) plays a
      pivotal role in IL-2-induced signal transduction, the function of the alpha
      subunit, other than modulating the association rate of IL-2, is still unknown. It
      has been reported that the interaction between IL-2 and the IL-2R alpha subunit
      of several IL-2-dependent murine T-cell lines may result in a negative regulatory
      signal. To confirm this finding, we investigated the effect of an anti-IL-2R
      alpha antibody, CD25-8D8, on the proliferative response of human peripheral blood
      lymphocytes. Lymphocytes from purified protein derivative (PPD)-positive donors
      were cultured with PPD and various concentrations of CD25-8D8 for up to 9 days,
      and [3H]thymidine uptake was measured. Whereas the proliferative response of
      human lymphocytes to PPD was suppressed by high concentrations of CD25-8D8,
      subinhibitory amounts of CD25-8D8 enhanced lymphocyte proliferation by 3.5-fold
      (range 2.2-6.2-fold) on the second day after maximal [3H]thymidine uptake had
      occurred. By itself, CD25-8D8 could not induce proliferation of washed 5-day PPD
      activated lymphocytes during reculturing; instead, growth enhancement by CD25-8D8
      was dependent on the presence of PPD-activated culture supernatant or moderate
      levels of exogenous IL-2. The enhancing effect of anti-IL-2R alpha antibody,
      observed in both murine and human systems, reinforces the possibility that
      binding of IL-2 to the IL-2R alpha chain plays a negative regulatory role in
      signal transduction.

PMID- 7821964
TI  - Influence of CD28 co-stimulation on cytokine production is mainly regulated via
      interleukin-2.
AB  - Interaction of CD28 with its ligand B7 plays an important role in the initiation
      of immune responses. The co-stimulatory signal generated by cross-linking of CD28
      molecules results in enhanced T-cell proliferation and augmentation of cytokine
      production. In particular, mRNA levels of T-helper 1 (Th1)-type cytokines, such
      as interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) are reported to be
      strongly increased. We investigated the effect of CD28 co-stimulation on the
      production of Th2-type cytokines. CD28 mAb induced a strong augmentation of IL-2
      secretion in activated T-cell clones. Production of IFN-gamma was also enhanced,
      but the increase in IL-4 secretion was generally moderate. Augmentation of IL-4
      production by CD28 was most pronounced in clones that produced low amounts of IL
      2, compared to clones producing high levels of IL-2. It was found that the up
      regulation of IL-4 by CD28 co-stimulation was mainly controlled indirectly via an
      increase of IL-2. Some clones could produce IL-4 in an IL-2-independent manner;
      in these situations CD28 co-stimulation had no augmenting effect on the
      production of IL-4. The secretion of IL-4 by peripheral blood CD4+ T cells, that
      were activated with B7-expressing transfectants, was also found to be dependent
      on IL-2. Finally, Northern blot analysis confirmed that co-stimulation of CD28
      primarily affected IL-2 production, and that inhibition of IL-2/IL-2 receptor
      interaction abolished the augmenting action of CD28 monoclonal antibody on the
      production of the Th2-type cytokines IL-4, IL-5 and IL-10 and of the Th1 cytokine
      IFN-gamma.

PMID- 7821965
TI  - Adoptive immunotherapy mediated by anti-TCR/IL-2-activated tumour-draining lymph
      node cells.
AB  - The adoptive immunotherapy of cancer with sensitized T lymphocytes is well
      documented in several animal models. These studies indicate the existence of
      precursor lymphocytes, in the tumour-bearing animals, which can acquire
      therapeutic efficacy after in vitro manipulations. To generate immune effector
      cells, these precursor lymphocytes have to be antigenically stimulated in vitro
      by the tumour of origin. Using the weakly immunogenic MCA 205 and MCA 203 murine
      sarcomas, we demonstrate here that this in vitro antigenic stimulation can be
      achieved by sequential activation with anti-T-cell receptor (TCR) monoclonal
      antibody and interleukin-2 (IL-2). The culture of tumour-draining lymph node
      (TDLN) cells with anti-TCR/IL-2 resulted in an up to eightfold increase in cell
      numbers. The adoptive transfer of these activated cells mediated a significant
      reduction of 3-day established pulmonary metastases. Although this antibody could
      activate all of the TCR alpha beta-bearing T cells non-specifically, the
      therapeutic efficacy mediated by anti-TCR/IL-2-activated cells was tumour
      specific. Treatment of MCA 205 advanced pulmonary metastases resulted in
      prolongation of survival, and 30% of treated mice were tumour free for more than
      90 days. These tumour-free mice rejected a challenge of MCA 205 but not MCA 203,
      indicating the development of long-lasting systemic tumour immunity. In spite of
      their in vivo anti-tumour efficacy, the anti-TCR/IL-2-activated TDLN cells did
      not exhibit detectable in vitro cytotoxicity. These results demonstrate that this
      activation method could be an alternative way to generating potent anti-tumour
      effector T cells.

PMID- 7821966
TI  - ICAM-1/LFA-1 interactions in T-lymphocyte activation and adhesion to cells of the
      blood-retina barrier in the rat.
AB  - To identify the signals involved in the adhesion and subsequent migration of
      lymphocytes across the endothelium (REC) and pigment epithelium (RPE) of the
      blood-retina barrier we have studied the effects of monoclonal antibodies (mAb)
      to rat adhesion/accessory molecules on the binding of normal and concanavalin A
      (Con A)-activated rat spleen lymphocytes to cultured unstimulated and interferon
      gamma (IFN-gamma)-stimulated RPE and REC. Forty to 48% of unactivated T cells
      were found to bind to normal REC or RPE by leucocyte function-associated antigen
      1/intercellular adhesion molecule-1 (LFA-1/ICAM-1)-independent mechanisms,
      despite constitutive expression of ICAM-1 by the RPE cells and LFA-1 by the T
      cells. Con A-activated lymphocytes showed an enhanced adhesion to both RPE and
      REC. However, IFN-gamma-stimulated RPE and REC did not demonstrate a significant
      increase in adhesiveness for normal lymphocytes highlighting the importance of
      lymphocyte integrin activation from low-affinity to high-affinity state.
      Activated lymphocyte adhesion to unstimulated RPE and REC was significantly
      blocked by LFA-1 mAb (35%, P < 0.0001) and ICAM-1 mAb (20%, P < 0.001).
      Inhibition of adhesion by antibody to CD2 was not significant. Both ICAM-1 and
      LFA-1 mAb also significantly (P < 0.05) blocked antigen presentation following
      retinal extract stimulation of lymphocytes from immunized rats in proliferation
      assay. These data suggest that the ICAM-1/LFA-1 system is important in lymphocyte
      trafficking into the eye only after lymphocyte activation.

PMID- 7821967
TI  - Hepatic regulation of lymphocyte adhesion to, and activation on, syngeneic
      endothelial monolayers.
AB  - Endothelial monolayers were prepared from neonatal heart or liver tissue of Lewis
      (Le) rats. Cells in their first passage of culture were used to investigate the
      short-term (1 hr at 37 degrees) binding of 51Cr-labelled Le rat lymphocytes
      prepared from the mesenteric lymph node (MLN), peripheral lymph node (PLN) or
      Peyer's patches (PP) to those endothelia, or the activation by concanavalin A
      (Con A) or irradiated (Lewis x Brown Norway)F1 (LBNF1), of Le cells on the
      monolayers after 84 hr in culture. MLN and PP showed preferential binding to, and
      activation on, liver endothelium compared with heart endothelium (approximately
      twofold difference), while the converse was seen with PLN. No inhibition of
      binding was seen with antibodies to intracellular adhesion molecule-1 (ICAM-1) or
      lymphocyte function-associated antigen-1 (LFA-1). Preincubation of endothelial
      cells with plasma isolated from the portal or hepatic vein of normal adult mice
      (5% plasma, 37 degrees for 14 hr) caused a 1.5-2-fold stimulation of binding of
      MLN/PP to heart endothelium, which was inhibited (> or = 75%) by anti-ICAM-1 or
      anti-LFA-1, and a fourfold stimulation of binding to liver endothelium, which was
      not inhibited by these monoclonal antibodies (< or = 25% inhibition). In
      contrast, antibodies to tumour necrosis factor-alpha (TNF-alpha) or interleukin-6
      (IL-6) caused inhibition of activation of liver endothelium (> or = 75%), while
      producing little affect on activation of heart endothelium. Similar results were
      seen when lymphocyte activation on endothelial cells rather than adhesion cells
      was investigated. Our data suggest a heterogeneity in lymphocyte-endothelial
      interactions, which is further regulated, under physiological conditions, by the
      liver.

PMID- 7821968
TI  - Platelet-activating factor and endotoxin induce tumour necrosis factor gene
      expression in rat intestine and liver.
AB  - We have shown previously that endotoxin, tumour necrosis factor (TNF) and
      platelet-activating factor (PAF) are important in the pathogenesis of bowel
      injury, and that endotoxin and TNF induce PAF formation in bowel tissue. In the
      present study we investigated the effects of endotoxin and PAF on TNF gene
      expression. Adult rats were injected with endotoxin (2 mg/kg), PAF (1
      microgram/kg) or endotoxin plus PAF, and were killed after 30 min. Endotoxin had
      little systemic effect. PAF induced transient hypotension and mild bowel injury.
      Endotoxin plus PAF caused profound shock, severe haemoconcentration, leukopenia
      and intestinal necrosis. Sham-operated rats had barely detectable TNF mRNA in the
      liver or intestine. Endotoxin or PAF induced a marked increase in TNF mRNA,
      especially in the distal ileum and in the liver, but much less in the jejunum.
      Endotoxin plus PAF did not further increase TNF mRNA, probably due to development
      of tissue injury. Serum TNF levels in animals treated with endotoxin, PAF and
      endotoxin plus PAF were elevated. Endotoxin induces TNF gene expression probably
      via both PAF-dependent and PAF-independent pathways, since TNF mRNA formation was
      only partially blocked by PAF antagonist.

PMID- 7821969
TI  - Signal transduction pathways involved in tumour necrosis factor secretion by
      Plasmodium falciparum-stimulated human monocytes.
AB  - Tumour necrosis factor (TNF) plays a pivotal role in the induction of cerebral
      complications during Plasmodium falciparum malaria. TNF secretion by macrophages
      can be induced by lipopolysaccharide (LPS) and by P. falciparum antigens, but it
      is unclear whether similar mechanisms control the monokine expression in both
      cases. The signal transduction pathway by which parasite antigens induce TNF
      secretion remains to be established. The results reported here, using various
      inhibitors of second messenger pathways, clearly demonstrate that the signal
      transduction leading to TNF secretion is mediated partly through protein kinase C
      and calmodulin-dependent protein kinase activation. Furthermore, this signal
      seems to be differentially regulated after LPS or parasite stimulation, since
      cyclo-oxygenase inhibition by indomethacin resulted in twofold more TNF
      production enhancement with LPS stimulation than with parasite stimulation. The
      nature of the receptor involved in the parasite induced-macrophage stimulation
      remains obscure. However, the results discussed here indicate that parasite
      antigens stimulate multiple signal transduction pathways via G protein.
      Identification of the different pathways involved in these receptor-mediated
      events may be invaluable in the development of specific inhibitors against TNF
      over-production during cerebral malaria.

PMID- 7821970
TI  - Protection against natural killer cells by interferon-gamma treatment of K562
      cells cannot be explained by augmented major histocompatibility complex class I
      expression.
AB  - Prior study has revealed that the expression of certain major histocompatibility
      complex (MHC) class I molecules on the membranes of normal or transformed cells
      can prevent natural killer (NK)-cell-mediated killing. This has been explained by
      either (1) the target interference model, or (2) the effector inhibition model.
      In both cases, MHC class I molecules are concerned but the precise mechanisms are
      still unclear. The erythroleukaemia K562 cell is known as a NK-sensitive target.
      This sensitivity has been explained mostly as being due to lack of MHC class I
      antigens on the K562 membrane. However, several recent studies have indicated
      that the expression of MHC class I antigens on the cell does not solely explain
      the protection against NK cells. To elucidate the mechanism of NK-cell-mediated
      killing, we investigated the killing profiles of the K562 cells by NK cells.
      Previous studies indicated that the NK-sensitive K562 cells can express some MHC
      class I antigens on their surface, and become protective against NK-cell killing
      after treatment with human interferon-gamma (hIFN-gamma). In the present study,
      we show that this resistance is not rendered by MHC class I expression, because
      addition of anti-MHC class I monoclonal antibodies (mAb) in the killing assay of
      hIFN-gamma-treated K562 cells, which express MHC class I antigens as the target,
      did not restore the sensitivity to NK cells. Moreover, we show that spontaneously
      occurring K562 clones which could not express MHC class I antigens even after
      hIFN-gamma treatment, could be protected after treatment with the cytokine. Taken
      together, these results strongly suggest that the susceptibility of K562 cells to
      NK cell killing is due to some elements distinct from those related to MHC class
      I antigens.

PMID- 7821971
TI  - Relationship of HIV-1 provirus load, CD8+ CD11+ T cells and HIV-1 envelope
      specific cytotoxic T lymphocytes in HIV-infected asymptomatic offients.
AB  - The course of human immunodeficiency virus (HIV) infection progresses from an
      acute infection, through a prolonged asymptomatic phase, to an immunocompromised
      state. Some of the possible mechanisms underlying immune dysfunction include
      decreased HIV-specific cytotoxic T lymphocyte (CTL) activity, increased
      suppressor T cells, and/or increased HIV load. However, no study has been carried
      out to correlate all these factors. In this study, 26 patients showed > 3 log DNA
      copy number/10(6) CD4+ T cells, and seven patients had < 3 log DNA copy/10(6)
      CD4+ T cells. Patients with higher virus load had greater than 15% (19-45%) CD8+
      CD11+ T cells. HIV-1 envelope-specific, HLA-restricted CTL activity (> 10%) was
      observed in 11 of 25 asymptomatic patients, and the remaining 14 patients lacked
      CTL activity (< 10%) in bulk assay. Although CTL activity was undetectable in
      these individuals, there was no significant difference in the frequency of
      activated CTL and their precursors in limiting dilution analysis. The patients
      with undetectable CTL activity had a higher percentage of CD8+ CD11+ T cells and
      a higher HIV-1 DNA copy number/million CD4+ T cells. Each of these parameters
      were significantly correlated with CD4+ T-cell numbers. The inverse relationship
      of CD8+ CD11+ T cells and virus load with HIV-specific CTL activity observed in
      this study may be one of the underlying factors which determines the course of
      HIV infection.

PMID- 7821972
TI  - Involvement of gamma delta T cells in immunity to trypanosomiasis.
AB  - In this study the involvement of peripheral gamma delta T cells, prepared by flow
      cytometry, in the immune response of cattle to primary infection with Trypanosoma
      congolense was assessed. Negligible in vitro proliferative responses were
      observed in gamma delta T cells isolated from trypanosusceptible Boran (Bos
      indicus) cattle at all stages examined post-infection when stimulated in vitro
      with parasite antigens. In contrast, both CD8+ T cells and gamma delta T cells
      from trypanotolerant N'Dama (Bos taurus) cattle proliferated markedly when
      stimulated in vitro with a complex of invariant trypanosome antigens with MW
      between 100,000 and 140,000 (100,000 MW complex). Neither species of cattle
      exhibited significant T-cell recognition of trypanosome variable surface
      glycoprotein (VSG). To study further the functional and phenotypic
      characteristics of the gamma delta T-cell response, four T-cell lines were
      established from infected N'Dama cattle. These cell lines were comprised of up to
      96% gamma delta (WC1+) T cells, the remainder being CD8+ T cells. Two of these
      gamma delta T-cell lines exhibited 100,000 MW complex antigen specificity which
      was not major histocompatibility complex (MHC) restricted in one line.

PMID- 7821973
TI  - MRL/lpr mice produce anti-Ro 52,000 MW antibodies: detection, analysis of
      specificity and site of production.
AB  - MRL/lpr mice are studied as one of the animal models of the human autoimmune
      disease Sjogren's syndrome. The mice develop inflammatory exocrinopathy
      resembling that of patients with Sjogren's syndrome. To investigate if MRL/lpr
      mice produce the anti-Ro/SS-A and anti-La/SS-B autoantibodies common to Sjogren's
      syndrome patients, mouse sera were tested in ELISA and Western blot with
      recombinant Ro 60,000 MW, Ro 52,000 MW and La antigen. Thirty per cent of mice
      aged 4 months and 5% of mice aged 2 months produced antibodies to human Ro 52,000
      MW. Antibodies to Ro 60,000 MW and La were found in a low percentage of the older
      mice but not at all in the younger mice. Immunohistological staining of mouse
      organ sections demonstrated anti-Ro 52,000 MW-producing cells in spleen, lymph
      nodes and salivary glands of seropositive animals. These findings provide further
      evidence for the usefulness of the MRL/lpr mouse as a model for Sjogren's
      syndrome.

PMID- 7821974
TI  - The effects of T cells and their products on in vitro healing of epitenon cell
      microwounds.
AB  - The purpose of the present investigation was to study the activity and behaviour
      of rat epitenon cells cultured in the presence of activated helper/inducer T
      lymphocytes and T-cell-derived cytokines interleukin-1 (IL-1), IL-2, transforming
      growth factor-beta (TGF-beta) and interferon-gamma (IFN-gamma). We measured the
      speed of healing of microwounded monolayers of epitenon cells as well as
      intercellular adhesion, cell proliferation and fibronectin production. The speed
      of monolayer healing was increased in the presence of activated CD4+ T
      lymphocytes and cytokines: TGF-beta > IL-2 > IL-1 > IFN-gamma. TGF-beta and IL-2
      were also found to promote cell-cell adhesion; other cytokines had a minor
      effect. IL-2, IL-1 and IFN-gamma promoted [3H]thymidine incorporation in epitenon
      cells whereas TGF-beta had an inhibitory effect. Fibronectin production was
      studied with immunofluorescence staining methods. Activated CD4+ T lymphocytes
      and TGF-beta stimulated the deposition of fibronectin whereas other cytokines did
      not have a significant effect. Our results suggest that activated T lymphocytes
      and T-cell-derived cytokines, especially IL-2 and TGF-beta play a crucial role in
      the regulation of epitenon cell proliferation, adhesion and extracellular matrix
      production during in vitro microwound healing. As epitenon cells are the main
      cell type participating in tendon repair, factors regulating their activity may
      find application in clinical practice.

PMID- 7821976
TI  - Differential rate of protein synthesis by antimesometrial and mesometrial
      decidual cells of rat.
AB  - Incorporation, in vitro, of labelled methionine into proteins of artificially
      induced decidual tissue shows the presence of an active protein synthetic
      machinery in the decidualising endometrium of rats. During the progressive phase,
      antimesometrial and mesometrial decidual cells, restricted to specific anatomical
      sites of the endometrium, synthesize proteins at varying rates and the rate of
      incorporation of methionine into proteins of mesometrial decidual cells is
      higher. Resolution of proteins on acrylamide gels following SDS electrophoresis
      shows qualitative changes in endometrial proteins at different stages of
      morphogenesis of decidual cells. Results are discussed in relation to
      characteristic morphological features of two decidual cell populations and
      differential gene expression in the decidualising endometrium.

PMID- 7821975
TI  - A human T-cell receptor recognizes 'O'-linked sugars from the hinge region of
      human IgA1 and IgD.
AB  - A receptor which binds secretory IgA (sIgA) is expressed on human T cells from
      patients with systemic lupus erythematosus, rheumatoid arthritis, Behcet's
      syndrome and IgA nephropathy and on normal T cells following phytohaemagglutinin
      (PHA) stimulation. The specificity of this receptor was initially probed with a
      panel of normal serum immunoglobulins in competitive inhibition assays with sIgA
      using two-colour immunofluorescence. While the receptor showed the strongest
      affinity for IgA1 (IC(50)10(-6) M), IgD which has a similarly glycosylated hinge
      region to IgA1, also bound to the receptor (IC50 10(-5) M). IgA2, which lacks the
      'O'-glycosylated hinge region, did not significantly inhibit the binding at these
      concentrations suggesting that the IgA determinants for this receptor might be
      the oligosaccharides present in the hinge region of IgA1. IgA1 has up to 10 'O'
      linked oligosaccharides and four N-linked oligosaccharides per molecule. In order
      to probe the role of the 'O'-linked hinge sugars in the binding event, a sugar
      library was prepared from IgA1 by a procedure designed to release 'O'-linked
      oligosaccharides preferentially, and to retain them in the natural closed ring
      formation. The sugars were released by hydrazinolysis at 65 degrees and the
      resulting oligosaccharide library analysed by high voltage paper electrophoresis
      (HVE) and P4 gel permeation chromatography. Competitive inhibition studies
      demonstrated that both the library and the individual 'O'-linked sugars
      associated with IgA1 were implicated in the binding of IgA1 to this receptor
      (IC50 between 1 x 10(-5) M and 6 x 10(-5) M). Within this range the individual
      sugars showed small differences in their affinity for the receptor in the
      following order: Gal beta 3GalNAc = NeuNAc2 alpha 3(6)Gal beta 3GalNAc > NeuNAc2
      alpha 3(6)Gal beta 3[NeuNAc2 alpha 6]GalNAc > or = GalNAc.

PMID- 7821977
TI  - Immunogenic activity of viral polypeptides of an Indian isolate of infectious
      bursal disease virus.
AB  - An Indian isolate of infectious bursal disease virus, i.e. IBDV-P/AD/81, was
      analysed for immunogenic activity of its structural polypeptides. Virus was
      purified from infected bursal homogenate by sucrose density gradient
      centrifugation. It showed five different structural polypeptides of 75.8, 45,
      40.7, 33.1 and 27 kDa molecular weights in sodium dodecyl sulphate polyacrylamide
      gel electrophoresis (SDS-PAGE). Anti infectious bursal disease virus (IBDV)
      antibodies were tested using enzyme-linked immunosorbent assay (ELISA) and
      neutralization test (NT). Polypeptide 40.7 kDa (VP2) was known to have
      neutralizing epitopes. However, polyclonal anti VP2 failed to neutralize the
      virus. It was interpreted that VP2 had labile neutralizing epitopes which get
      altered confirmationally by SDS. Surprisingly, polyclonal anti 33.1 kDa (VP3) had
      mild neutralizing activity.

PMID- 7821978
TI  - Effect of size and shape of the allogeneic bone grafts in bridging experimental
      ulnar gap in rabbits.
AB  - Partially decalcified allogeneic bone matrix was cut into the sizes and shapes of
      cylinders, bone strips and pulverized bone powder. Large osteoperiosteal gaps
      were created in rabbit's ulnae. A total of 14 gaps were filled with bone strips,
      20 with powder, six with cylinders and two were left unbridged to serve as
      control. The healing of gap was assessed at intervals with a maximum follow up of
      24 weeks. Clinically at 12 weeks the bone strips could not be moved separately
      from each other, the whole tubular bone had also united whereas gaps filled with
      bone powder did not diminish in size. Radiologically union occurred earlier
      (around 12 weeks) in bone strips as compared to cylinders (approx-18 weeks). With
      bone powder only a faint line of the remnants was visible. Gross examination
      findings of the grafted area were in concurrence with the clinical and
      radiological findings. Overall the gaps filled with bone strips had 100 per cent
      success with early osteo induction and remodelling as compared to long cylinders
      whereas gaps filled with bone powder had complete failure.

PMID- 7821979
TI  - Down regulation of tumour necrosis factor activity in experimental hepatitis by a
      herbal formulation, Liv. 52.
AB  - A herbal hepatoprotective formulation Liv 52 down regulated the tumour necrosis
      factor (TNF) production in Charles Foster Rats treated with CCl4. Inhibition of
      TNF activity was proportional to the hepatoprotective activity.

PMID- 7821980
TI  - Changes in Na and K ions in mouse liver following in vivo exposure to ultrasound.
AB  - Mouse liver was exposed in vivo to a continuous and unfocussed ultrasound of 875
      KHz at 5, 10 or 15 W/cm2 for 300 sec spread over five days and excised on day 0,
      1, 5 and 10 for studying the changes in Na+ and K+ reserves and Na-K-ATPase
      activity. At 5 and 10 W intensities the change in ionic concentrations and Na-K
      ATPase activity were almost in linear. At 15 W intensity the loss of both the
      ions and suppression of Na-K-ATPase indicated the damage of hepatic tissue caused
      by high intensity ultrasound. By day 10, all the animals of three exposures
      showed a normal ionic concentration with an optimum Na-K-ATPase activity in liver
      indicating the recovery process. The results indicate that ultrasound induces
      permeability changes in a glandular tissue exposed in vivo.

PMID- 7821981
TI  - Studies on peripheral actions of isatin.
AB  - The possible peripheral actions of isatin were studied in vivo and in vitro
      preparations in different experimental models, using conventional techniques. The
      results showed spasmogenic responses of isatin on guinea pig, rat and rabbit
      ileum and fundus of rat stomach. Histamine induced broncho-constriction could be
      antagonised by isatin. Isatin had cardioinhibitory effect on isolated frog heart
      and had hypotensive and respiratory depressant activities in dog. Isatin had
      antidiuretic effect. It was devoid of any effect on inflammation and gastric
      activities. The present results suggest a possible involvement of heterogenic 5
      HT3 receptors in gastrointestinal smooth muscle.

PMID- 7821982
TI  - Antinociceptive action of N-octanoyl GABA--a new GABA mimetic agent.
AB  - A new derivative of gamma-aminobutyric acid (GABA) was synthesized. The compound,
      N-octanoyl GABA (O-GABA), exhibited positive analgesic response in four different
      models in mice--tail immersion, hot plate, tail clip and acetic acid induced
      writhing. The antinociceptive activity was significantly blocked by picrotoxin
      but not by bicuculline or 3-mercaptopropionic acid. Naloxone failed to reverse
      the antinociceptive response of O-GABA but a synergistic action was observed with
      pethidine. Pretreatment with atropine significantly reduced the antinociceptive
      action of O-GABA. Biochemical tests revealed that O-GABA significantly increased
      brain GABA levels.

PMID- 7821983
TI  - Effects of DSP-4-induced depletion of brain norepinephrine on appetitive and
      aversive memory retrieval.
AB  - This study examined whether depletion of central norepinephrine produces an
      improved retrieval of aversive memories in the same way as pre-exposure to
      inescapable footshocks, in rats. Animals conditioned in a T-maze with appetitive
      (10% sucrose) and aversive (2.0 mA footshock) events were given a single dose of
      DSP-4 (100, 200 or 400 micrograms/rat) or drug vehicle ICV 24 hr later. The
      retention performance and activity were assessed 48 hr after the treatment with
      this neurotoxin. DSP-4 had no effect on open field activities but enhanced
      latencies to enter both, previously shocked and appetitively reinforced,
      goalboxes. The data thus, suggest that central administration of DSP-4 does not
      result in selective enhanced aversive memories. On the contrary, post-trial NE
      depletion with this neurotoxin might interfere with the retrieval of previously
      learned association with appetitive stimuli. DSP-4 significantly reduced
      monoamines, depending upon the brain regions assayed and the doses studied.
      However, only decreased NE in striatum coincided with the memory changes
      suggesting that NE innervation to striatum may participate in the retrieval
      process.

PMID- 7821984
TI  - p-Aminobenzene sulphonyl morpholine, compound 82/208 a new anticonvulsant agent.
AB  - p-Aminobenzene sulphonyl morpholine, compound 82/208, was evaluated for acute
      toxicity and anticonvulsant action in mice against tonic seizures induced by
      supramaximal electroshock and pentylene tetrazole and strychnine induced seizures
      and for its effect on blood pressure and respiration in cat. Diphenyl hydantoin
      (DPH) was used as reference standard. Compound 82/208 exhibited anticonvulsant
      activity against electroshock induced seizures and PTZ induced tonic seizures in
      mice. The compound had several distinct advantages over DPH in experimental
      evaluation in mice.

PMID- 7821985
TI  - Some naturally occurring phytophototoxins for mosquito control.
AB  - Alpha-terthiophene (alpha-T) and erythrosin-B, the naturally occurring plant
      secondary metabolites, were tried for their phototoxic properties against
      Anopheles and Culex larvae under dark, ordinary tube light (1.9-2.4 w/m2) and sun
      light (680-840 w/m2). LC50 values of alpha-T for Anopheles larvae (4th instar)
      were found to be 154, 92 and 11 ppb under dark, tube light and sunlight,
      respectively. For Culex larvae corresponding LC50 values under different light
      conditions were 129, 97 and 22 ppb. Erythrosin-B under all photoregimens was
      found to be less toxic to larvae of both Anopheles and Culex sps. Also, the
      susceptibility of the mosquito species decreased with age, towards alpha-T and
      erythrosin-B. Cumulative effects in terms of delay in metamorphosis were also
      observed among survivors of such exposures. The effects of these compounds were
      also seen on the adults and developing unhatched embryos of a common aquatic
      snail (Lymnaea sps). The LC50 values of alpha-T for adults were found to be 39,
      23 ppm and 77 ppb under dark, tube light and sunlight and for developing
      unhatched embryos the corresponding values were 620, 41 and 13 ppb. Erythrosin-B
      was found to be much less toxic under sunlight and dark, to both adults and
      embryos as compared to the toxicity of alpha-T. Potential use of such
      biodegradable and eco-friendly compounds of natural origin in mosquito control is
      discussed.

PMID- 7821986
TI  - Subacute toxicity of fenvalerate in broiler chicks: concentration, cytotoxicity
      and biochemical profiles.
AB  - Subacute toxicity study of fenvalerate was carried out in broiler chicks after
      oral administration @ 525.6 mg/kg once daily for 28 days. The blood concentration
      of fenvalerate following 1 day post-administration (pd) was 39.65 +/- 2.67
      micrograms/ml and maintained plateau thereafter up to day 21 pd, and then
      declined (18.46 +/- 1.47 micrograms/ml) on day 28 pd. Intestine contained maximum
      residue (7.46 +/- 1.96 micrograms/g) followed by fat (5.95 +/- 1.16
      micrograms/g), brain (5.06 +/- 0.96 micrograms/g), liver (3.93 +/- 0.51
      micrograms/g), kidney (3.79 +/- 0.72 micrograms/g) and heart (1.72 +/- 0.35
      micrograms/g). Histopathological examinations showed focal areas of necrosis in
      liver, proliferation and fibrosis of bile duct, larger size of glomeruli,
      glomerular and tubular necrosis in treated birds. Fenvalerate significantly
      increased the cholesterol level in brain, GPT activity in liver and heart, GOT
      activity in heart, and alkaline phosphatase activity in heart and brain tissue.
      It significantly decreased the glycogen content in liver and heart, GOT activity
      in brain and acid phosphatase activity in all the tissues analyzed. It appears
      that comparatively fowl is resistant to fenvalerate toxicity.

PMID- 7821987
TI  - Modulation of resistance to chloroquine by ascorbic acid and cyproheptadine in
      Plasmodium berghei in vivo.

PMID- 7821988
TI  - Effect of ethyl 2-cyanoacrylate adhesive on rabbit vaginal mucous membrane.

PMID- 7821989
TI  - Future issues in health care reform.

PMID- 7821990
TI  - The ghost of health care future.

PMID- 7821991
TI  - The distributional effects of employer and individual health insurance mandates.
AB  - This paper assesses the impact of different kinds of employer and individual
      mandates on the cost to individuals, business, and government. We also examine
      the distribution of health care expenditures across individuals in different
      income groups, assuming that individuals ultimately bear the cost of employer
      payments through lower wages and the cost of government payments through tax
      contributions. A major conclusion is that net benefits to lower income
      individuals improve under all alternatives to the current system with relatively
      small increases in payments by individuals in any income group. Additionally,
      while employer mandates reduce individuals' direct payments, individual mandates
      can have lower costs to the government and better distributional outcomes. A 50%
      employer mandate also has many desirable features.

PMID- 7821992
TI  - Supplementing managed competition.
AB  - President Clinton's proposal for health care reform calls for managed competition
      within global expenditure targets. However, it is unlikely that health plans will
      have sufficient leverage with providers to negotiate arrangements consistent with
      expenditure targets in nonurban areas. This paper describes a reimbursement
      system based on competitive prospective payment and capitation (CPPC) which can
      supplement managed competition in less populous areas or replace managed
      competition should that strategy prove unsuccessful. The CPPC system is capable
      of enforcing an expenditure target while encouraging the formation of capitated
      networks and creating strong incentives for efficiency. It is generally
      compatible with the Clinton administration's version of managed competition.

PMID- 7821993
TI  - Physician income targets: new evidence on an old controversy.
AB  - This study uses a unique set of data to identify the factors that affect
      physician income targets among a nationally representative sample of young (under
      age 40) physicians in 1987. The study reveals that income targets respond
      directly to actual income, but that this relationship is rather inelastic. Among
      self-employed physicians, for example, a 10% decline in actual income would
      reduce the target by only 3%. Thus, our study provides the first direct evidence
      to quantify how a decline in income will increase the divergence between actual
      and target income. Moreover, in quantifying this divergence, our results provide
      an upper bound on the dollar value of any demand inducement that may ensue. The
      results suggest that targets are set, at least in part, to compensate physicians
      for pecuniary and nonpecuniary costs associated with medical practice.
      Discrimination, dissatisfaction, financial risks, and training costs all appear
      to raise income targets. Physicians may desire higher incomes to compensate them
      for discrimination or other difficulties they have encountered in practicing
      medicine.

PMID- 7821994
TI  - The uninsured access gap: narrowing the estimates.
AB  - Measuring the cost of universal coverage requires estimates of the uninsured
      access gap--the additional care that the uninsured would consume. Estimates of
      this gap from existing literature span a wide range. Using databases that are the
      source of these estimates, this paper explores differences that might account for
      the range of estimates including time, populations, control variables, and
      definitions. Adjusting for these differences, estimates of the uninsured access
      gap are considerably narrowed. The new estimates indicate that health consumption
      by the uninsured would increase 50%--implying an increase in total health care
      spending of about 2%.

PMID- 7821995
TI  - Are subsidies enough to encourage the uninsured to purchase health insurance? An
      analysis of underlying behavior.
AB  - A growing concern over gaps in health insurance coverage has led to proposals for
      reform. Some proposals rely on incentives to encourage the purchase of private
      health insurance, while others rely on mandatory purchase. This paper explores
      families' demand for private health insurance, with an emphasis on lower income
      families, in order to understand the factors that affect purchasing decisions.
      The study uses data from the 1977 National Medical Care Expenditure Survey to
      show which factors are important in determining whether or not families purchase
      private health insurance as well as the quantity of insurance purchased. Results
      indicate that it is the combination of income, price, and substitutes for private
      health insurance that impact families' decision to purchase private health
      insurance. As long as a safety net of substitutes exists for low-income families,
      subsidies may not be enough to encourage more extensive private health insurance
      coverage.

PMID- 7821996
TI  - Health insurance and health status: implications for financing health care
      reform.
AB  - Self-reported health status measures from the 1987 National Medical Expenditure
      Survey indicate significant differences among each of five population groups
      defined by current health insurance coverage. These differences in health status
      imply that the groups are likely to exhibit different patterns of expenditures,
      even if enrolled in the same health insurance after health care reform. The
      healthiest group along most dimensions is the population covered by employer
      sponsored insurance, followed in order by the population with nongroup private
      insurance, the uninsured population, the population that qualifies for public
      coverage based on income, and the population that qualifies for public coverage
      based on medical need. While the general health and mental health of the
      uninsured are slightly worse in comparison to the privately insured, the
      uninsured have fewer chronic health problems. The uninsured who recently lost
      private insurance or who live in working families are significantly healthier
      than the long-term or low-income and nonworking uninsured.

PMID- 7821997
TI  - Premium elasticities of health plan choice.
AB  - We estimate out-of-pocket premium elasticities of health plan choice using panel
      data from five Twin Cities employers. Using simple methods and a small data set,
      we replicate the findings of our previous study, which was considerably more
      detailed, difficult, and expensive. An increase of $5 in 1984 dollars ($6.95 in
      1993) in the relative out-of-pocket premium for single coverage is predicted to
      decrease that plan's share of the single coverage market by .112 percentage
      points. The corresponding elasticity is approximately -7.9. This simple analysis
      should be repeated by other analysts in their market areas to determine the
      consistency of findings across geographic areas and over time.

PMID- 7821998
TI  - Asymmetric information and the demand for Medigap insurance.
AB  - The Medigap insurance market has been characterized as having considerable cross
      policy variation in contract design and relatively high premiums vis-a-vis
      average risk exposure. One explanation for these characteristics is that adverse
      selection exists in the Medigap market. The purpose of this study is to
      investigate adverse selection effects among those purchasing Medigap insurance.
      Findings are consistent with the presence of adverse selection in the Medigap
      market and premium cross-subsidization from low- to high-risk insured
      individuals.

PMID- 7821999
TI  - Antibodies to capsular polysaccharides are not protective against experimental
      Staphylococcus aureus endocarditis.
AB  - The protective efficacy of antibodies to the Staphylococcus aureus capsular
      polysaccharide was examined in a rat model of catheter-induced endocarditis.
      Capsular antibodies were induced either by active immunization with killed S.
      aureus or by passive immunization with hyperimmune rabbit antiserum to S. aureus.
      Control rats were injected with phosphate-buffered saline or passively immunized
      with normal rabbit serum or rabbit antiserum to a nonencapsulated strain. Animals
      with indwelling catheters were challenged intravenously with 5 x 10(4) to 4 x
      10(6) CFU of the homologous S. aureus strain (capsular serotype 5 strain Reynolds
      or serotype 1 strain SA1 mucoid). Both immunized and control rats developed S.
      aureus endocarditis. The numbers of S. aureus cells recovered from the blood and
      aortic valve vegetations of immunized rats were similar to those of control rats,
      indicating that capsule-specific antibodies were not protective. To determine
      whether the presence of an indwelling catheter interfered with antibody-mediated
      protection against S. aureus endocarditis, catheters were removed 2 h after
      insertion in additional groups of rats. An inoculum of 10(8) CFU of strain
      Reynolds was needed to provoke endocarditis in rats catheterized for 2 h,
      compared with 5 x 10(4) CFU for rats with indwelling catheters. Passively
      transferred capsular antibodies were not protective since both immunized and
      nonimmunized animals developed endocarditis, and quantitative cultures of blood
      and valvular vegetations revealed no differences between immunized and control
      animals. The findings of this study indicate that antibodies to the capsular
      polysaccharide are not protective in the rat model of experimental S. aureus
      endocarditis.

PMID- 7822000
TI  - Induction of inflammatory cytokines in bovine alveolar macrophages following
      stimulation with Pasteurella haemolytica lipopolysaccharide.
AB  - Bovine tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta)
      cDNAs were generated by reverse transcription and then by PCR amplification from
      lipopolysaccharide (LPS)-stimulated alveolar macrophage RNA. The amplified cDNAs
      were cloned into pPow and expressed in Escherichia coli DH5 alpha. The expressed
      proteins were confirmed as TNF-alpha and IL-1 beta by Western blot (immunoblot)
      analysis and bioassays. We then used the cloned genes as probes in Northern (RNA)
      blots and investigated the kinetics of TNF-alpha and IL-1 beta mRNA expression in
      bovine alveolar macrophages stimulated with purified LPS from Pasteurella
      haemolytica 12296. The effect of LPS on TNF-alpha and IL-1 beta gene expression
      was dose dependent, and induction was observed at a concentration of 0.01
      microgram/ml. Both TNF-alpha and IL-1 beta mRNA expression were detectable within
      0.5 h after stimulation with 1 microgram of LPS per ml, peaked at 1 to 2 h,
      steadily declined up to 16 h, and were undetectable by 24 h. Secreted TNF-alpha
      measured by bioassay peaked at 4 h and accumulated at a lesser concentration in
      conditioned medium throughout the 24 h. By contrast, secreted IL-1 beta was
      induced at 8 h and reached a maximal concentration at 24 h after stimulation. The
      ability of LPS to induce TNF-alpha and IL-1 beta gene expression and secretion of
      bioactive proteins were suppressed by polymyxin B. Our findings support a role
      for LPS from P. haemolytica in the induction of inflammatory cytokines in bovine
      pneumonic pasteurellosis.

PMID- 7822001
TI  - Subjects recovering from human ocular chlamydial infection have enhanced
      lymphoproliferative responses to chlamydial antigens compared with those of
      persistently diseased controls.
AB  - Cell-mediated immune responses to chlamydial and common recall antigens were
      measured in 26 subjects whose clinical signs of trachoma persisted over 6 months
      of follow-up and in 21 subjects whose clinical signs resolved spontaneously over
      the same period. Seven-day lymphocyte proliferative responses to chlamydial but
      not common recall antigens were significantly greater in subjects whose disease
      resolved spontaneously. There was, however, no detectable difference between the
      two groups in gamma interferon levels in supernatants from lymphocyte cultures
      stimulated with these antigens. These results are consistent with the hypothesis
      that cell-mediated immune responses play an important role in the clearance of
      ocular chlamydial infection in humans.

PMID- 7822002
TI  - Resistance of a Tn4351-generated polysaccharide mutant of Porphyromonas
      gingivalis to polymorphonuclear leukocyte killing.
AB  - In this study, we describe the development of an efficient transpositional
      mutagenesis system for Porphyromonas gingivalis using the Bacteroides fragilis
      transposon Tn4351. Using this system, we have isolated and characterized a Tn4351
      generated mutant of P. gingivalis A7436, designated MSM-1, which exhibits
      enhanced resistance to polymorphonuclear leukocyte (PMN) phagocytosis and
      killing. P. gingivalis MSM-1 was initially selected based on its colony
      morphology; MSM-1 appeared as a mucoid, beige-pigmented colony. Analysis of P.
      gingivalis MSM-1 by electron microscopy and staining with ruthenium red revealed
      the presence of a thick ruthenium red-staining layer that was twice the thickness
      of this layer observed in the parent strain. P. gingivalis MSM-1 was found to be
      more hydrophilic than strain A7436 by hydrocarbon partitioning. Analysis of
      phenol-water extracts prepared from P. gingivalis A7436 and MSM-1 by Western
      (immunoblot) analysis and immunodiffusion with hyperimmune sera raised against
      A7436 and MSM-1 revealed the loss of a high-molecular-weight anionic
      polysaccharide component in extracts prepared from MSM-1. P. gingivalis MSM-1 was
      also found to be more resistant to PMN phagocytosis and intracellular killing
      than the parent strain, as assessed in a fluorochrome phagocytosis microassay.
      These differences were statistically significant (P < 0.05) when comparing PMN
      phagocytosis in nonimmune serum and intracellular killing in nonimmune and immune
      sera. P. gingivalis MSM-1 was also more resistant to killing by crude granule
      extracts from PMNs than was P. gingivalis A7436. These results indicate that the
      increased evasion of PMN phagocytosis and killing exhibited by P. gingivalis MSM
      1 may result from alterations in polysaccharide-containing antigens.

PMID- 7822003
TI  - A tissue culture bilayer model to study the passage of Neisseria meningitidis.
AB  - A tissue culture bilayer system has been developed as a model to study the
      mechanisms of attachment and invasion involved in the pathogenesis of Neisseria
      meningitidis. The model incorporates epithelial and endothelial cell layers
      separated by a microporous membrane and makes it possible to observe and quantify
      the passage of bacteria through the multiple layers and to study the mechanisms
      by which they make this passage. This model is adaptable to a wide variety of
      microbial pathogens and can be modified by substituting any physiologically
      relevant eucaryotic cells for the component layers. The system's makeup of cells
      of human origin and its reproducibility give it advantages over animal and
      primary organ culture models, while the added complexity of multiple layers
      allowing cell-to-cell communication makes it a more realistic human tissue model
      than standard cell monolayers.

PMID- 7822004
TI  - Immunoglobulin G1 (IgG1) and IgG3 antibodies are markers of progressive disease
      in leprosy.
AB  - Mycobacterium leprae-specific and polyclonal immunoglobulin G (IgG) subclass and
      IgE antibodies in leprosy patients across the histopathological spectrum were
      determined by using a quantitative enzyme-linked immunosorbent assay. Antibody
      responses to M. leprae sonicates were detected only in IgG1, -2, and -3
      subclasses. Even at 100-times-lower dilutions, very little IgG4 and IgE antibody
      activity against M. leprae was detected in any group of leprosy patients.
      Quantitatively, antibody responses were highest at the lepromatous pole and
      decreased towards the tuberculoid pole. The greatest quantitative difference in
      antibodies between the lepromatous and tuberculoid poles was observed with IgG1
      (140-fold), this was followed by the difference with IgG3 antibodies (32-fold).
      Polyclonal antibodies, on the other hand, were elevated for all four IgG
      subclasses as well as IgE in both lepromatous and tuberculoid leprosy patients
      compared with healthy controls from a leprosy-endemic area. Selective elevation
      of M. leprae-specific antibody responses in IgG1 and IgG3 subclasses, therefore,
      could not be attributed to selective polyclonal activation in these particular
      subclasses. Furthermore, polyclonal activation for IgE was observed in both
      lepromatous and tuberculoid leprosy patients, with higher levels in the
      tuberculoid group, which does not support selective TH2 activation in lepromatous
      leprosy patients. IgG1 and IgG3 antibodies also showed the highest Spearman rank
      correlation with the bacterial index in these patients (rho = 0.748 and P < 0.001
      for IgG1; rho = 0.721 and and P < 0.001 for IgG3). Thus, disease progression in
      leprosy showed a significant correlation with selective increases in IgG1 and
      IgG3 responses.

PMID- 7822005
TI  - Binding of type 1-piliated Escherichia coli to vaginal mucus.
AB  - To better understand the interactions involved in bacterial adherence and the
      role of mucus in the pathogenesis of urinary tract infections, we developed a
      system to study the binding of a recombinant Escherichia coli strain, HB101/pWRS1
      17, expressing type 1 pili, to vaginal mucus collected from 28 women. Bacteria
      bound to differing extents to all specimens examined, and preincubation of
      bacteria with mannose inhibited binding by 50 to 89%. Additionally, all mucus
      samples showed reactivity with anti-mannose antibody, and the levels of
      reactivity correlated with the levels of bacterial binding, suggesting that the
      mannose-terminal saccharides present on these glycoproteins are the receptors for
      the binding of type 1-piliated bacteria. Mucus specimens collected over periods
      of 5 days and 12 weeks exhibited significant variation in bacterial binding,
      indicating temporal differences in the ability of vaginal mucus to act as a
      receptor for type 1-piliated E. coli. The results show that vaginal mucus can
      bind bacteria and may thus influence the initial attachment and subsequent
      colonization of the vaginal and urinary tract epithelium by E. coli.

PMID- 7822006
TI  - Staphylococcal enterotoxin A and toxic shock syndrome toxin compete with CD4 for
      human major histocompatibility complex class II binding.
AB  - We have examined the role of the CD4 molecule in primary T-lymphocyte responses
      to the staphylococcal enterotoxins SEA, SEB, SEC1, and the toxic shock syndrome
      toxin TSST-1. Proliferating cells were predominantly CD4+; however, the responses
      to SEA and TSST-1 were most sensitive to inhibition by the anti-CD4 antibody Leu
      3a. T-lymphocyte responses to the bacterial superantigens were inhibited by site
      directed mutations of residues in the DR beta membrane-proximal domain (DR beta
      2) that are also known to be important for interactions with CD4. SEA and TSST-1
      binding to DR was reduced by the DR beta 2 mutations and by competition with
      soluble recombinant CD4. We propose that bacterial superantigens sequentially, or
      simultaneously with CD4, stabilize complexes of T-cell antigen receptors and
      major histocompatibility complex class II molecules. The superantigen qualities
      of these toxins may be due, in part, to a molecular mimicry of CD4 and other
      adhesion molecules.

PMID- 7822007
TI  - Identification of a new intestinal spirochete with pathogenicity for chickens.
AB  - Two intestinal spirochete isolates obtained from chickens with diarrhea were
      examined by electron microscopy, biochemical tests, rRNA gene restriction pattern
      analysis, and multilocus enzyme electrophoresis. One isolate (strain 91-1207/C1)
      was pathogenicity tested in vivo in chickens. The chicken spirochetes were
      morphologically indistinguishable from Serpulina innocens and Serpulina
      hyodysenteriae and phenotypically similar to S. innocens. However, the chicken
      spirochetes could be distinguished from S. innocens, S. hyodysenteriae, and other
      swine intestinal spirochetes by rRNA gene restriction pattern analysis and
      multilocus enzyme electrophoresis. In pathogenicity tests in 1-day-old chicks and
      14-month-old hens, chicken spirochete 91-1207/C1 produced pale-yellow, watery
      cecal contents and mild lymphocytic typhlitis. These findings support the
      conclusion that avian intestinal spirochetes can be pathogenic to commercial
      poultry and that the microorganisms are different from intestinal spirochetes
      that infect pigs.

PMID- 7822008
TI  - Interaction of pneumolysin-sufficient and -deficient isogenic variants of
      Streptococcus pneumoniae with human respiratory mucosa.
AB  - Streptococcus pneumoniae is the most common cause of community-acquired
      pneumonia, and pneumolysin, a hemolytic toxin, is thought to be an important
      virulence factor. We have studied the interaction of a pneumolysin-sufficient
      type II S. pneumoniae strain (PL+) and an otherwise identical pneumolysin
      deficient derivative (PL-) with human respiratory mucosa in an organ culture with
      an air interface for up to 48 h. Ciliary beat frequency (CBF) was measured by a
      photometric technique, and adherence to and invasion of the epithelium were
      assessed by scanning and transmission electron microscopy. PL+ and PL- caused a
      progressive fall in CBF compared with the control which became significant (P <
      0.01) at 24 h for PL+ and at 48 h for PL-. At 24 h, there was a significant
      increase in the percentage of the mucosa of the organ culture that was damaged
      for PL+ compared with the control (P < 0.01) and PL- (P < 0.02). At 48 h, there
      was a significant increase in mucosal damage for both PL+ (P < 0.005) and PL- (P
      < 0.05) compared with the control. At 24 and 48 h, PL+ and PL- adhered
      predominantly to mucus and damaged cells. PL+ infection alone caused separation
      of tight junctions between epithelial cells, and at 48 h PL+ cells were adherent
      to the separated edges of otherwise healthy unciliated cells. PL+ and PL- both
      caused damage to the epithelial cell ultrastructure. S. pneumoniae infection
      caused patchy damage to the respiratory mucosa and a lowered CBF. These changes
      were more severe and occurred earlier with the pneumolysin-sufficient variant.

PMID- 7822009
TI  - A pneumolysin-negative mutant of Streptococcus pneumoniae causes chronic
      bacteremia rather than acute sepsis in mice.
AB  - Pneumolysin is a cytoplasmic virulence factor of Streptococcus pneumoniae that
      can interfere with phagocyte function in vitro. We have examined the effects of
      pneumolysin in vitro and in vivo and have found that it protects intravenously
      injected pneumococci against infection-induced host resistance. We employed a
      virulent capsular type 2 pneumococcal strain, D39, and its isogenic pneumolysin
      negative mutant, PLN. Strain D39 exhibited exponential net growth in mice
      (doubling time, 1.4 h); 24 to 28 h after infection with 10(4) CFU, the numbers of
      pneumococci reached 10(9) to 10(10) CFU/ml and the mice died. Strain PLN yielded
      identical net growth in mice until reaching 10(6) to 10(7) CFU/ml at 12 to 18 h
      postinfection. At this time, the increase in the level of PLN CFU per milliliter
      ceased and remained constant for several days. PLN exhibited wild-type growth
      kinetics in mice when coinfected simultaneously with strain D39. This observation
      suggests that pneumolysin exerts its effects at a distance. By 12 to 18 h
      postinfection with PLN, mice exhibited the following evidence of an induced
      inflammatory response: (i) elevated plasma interleukin-6, (ii) a halt in the net
      growth of PLN, and (iii) control of the net growth of pneumolysin-producing D39
      pneumococci upon subsequent challenge. Our data suggest that pneumolysin plays a
      critical role in sepsis during the first few hours after infection by enabling
      pneumococci to cause acute sepsis rather than a chronic bacteremia. However, once
      chronic bacteremia was established, it appeared that pneumolysin was no longer
      able to act as a virulence factor.

PMID- 7822011
TI  - Transmission blockade of Plasmodium falciparum malaria by anti-Pfs230-specific
      antibodies is isotype dependent.
AB  - By use of the parental hybridoma cell line 63F2A2 that produces specific
      antibodies of immunoglobulin isotype G1 (IgG1; 63F2A2.1) against Pfs230, we
      attempted to enrich for the synthesis of the downstream switch variant IgG2b and
      IgG2a monoclonal antibodies (MAbs) of the hybridoma cell line (63F2A2.2b and
      63F2A2.2a, respectively). The parental IgG1 did not reduce the Plasmodium
      falciparum transmission in a bioassay irrespective of the presence of complement.
      MAbs 63F2A2.2b and 63F2A2.2a were effective in reducing the infectivity of P.
      falciparum parasites to Anopheles gambiae mosquitoes in membrane-feeding
      experiments. A transmission reduction of 91% was accomplished by the 63F2A2.2b
      switch variant, and a reduction of greater than 99% was accomplished by the
      63F2A2.2a switch variant, but only in the presence of active human complement.
      Subsequently, the transmission-reducing effect of MAb 63F2A2.2b or 63F2A2.2a was
      confirmed in vitro by the rapid lysis of newly formed macrogametes or zygotes in
      the presence of active complement. MAb 63F2A2.1 did not lyse the newly formed
      macrogametes or zygotes irrespective of the presence of complement.

PMID- 7822010
TI  - Serum antibodies from malaria-exposed people recognize conserved epitopes formed
      by the two epidermal growth factor motifs of MSP1(19), the carboxy-terminal
      fragment of the major merozoite surface protein of Plasmodium falciparum.
AB  - The major merozoite surface protein of Plasmodium falciparum (PfMSP1) is a
      candidate antigen for a malaria vaccine. A 19-kDa C-terminal processing product
      of PfMSP1 (PfMSP1(19)) is composed of two domains sharing a cysteine-rich motif
      with epidermal growth factor (EGF) and is the target of monoclonal antibodies
      which block erythrocyte invasion in vitro. We have evaluated human antibody
      responses to PfMSP1(19) by using recombinant proteins representing the EGF motifs
      encoded by the two main alleles of the MSP1 gene. We find that both EGF motifs
      are antigenic but that only 10 to 20% of malaria-exposed individuals have serum
      antibodies that recognized either of the motifs. When both EGF motifs were
      expressed together as a single protein, they were recognized by more than 40% of
      sera from malaria-exposed individuals. Major epitopes recognized by human
      antibodies are dependent upon the correct tertiary structure of the protein and
      are cross-reactive between the different allelic sequences of PfMSP1(19). This
      suggests that antibodies induced by vaccination with one or the other allelic
      forms of the protein could recognize all strains of P. falciparum. Immunoglobulin
      G (IgG) subclass-specific enzyme immunoassays indicate that PfMSP1(19) antibodies
      are predominantly of the IgG1 subclass.

PMID- 7822012
TI  - Protection of gerbils from amebic liver abscess by immunization with recombinant
      Entamoeba histolytica 29-kilodalton antigen.
AB  - The goal of our study was to obtain a highly conserved Entamoeba histolytica
      recombinant antigen for study as a subunit amebiasis vaccine. We screened a Uni
      Zap cDNA library of E. histolytica (strain HM1:IMSS) with human immune sera and
      isolated a dominant 804-bp cDNA clone. A 33-kDa fusion protein expressed from the
      cDNA clone was determined by monoclonal antibody binding, DNA hybridization, and
      nucleotide sequence to be the complete E. histolytica 29-kDa antigen. Serum
      antibodies to the recombinant protein were detected by enzyme-linked
      immunosorbent assay in 80% of subjects from Egypt and South Africa with amebic
      liver abscess. Similar results were found with the native 29-kDa protein. Native
      and recombinant 29-kDa antigens induced proliferation of lymphocytes harvested
      from patients with amebic liver abscess (P < 0.01 compared with controls).
      Intraperitoneal immunization of gerbils with the recombinant fusion protein (10
      micrograms) with Titermax adjuvant elicited an antigen-specific serum
      immunoglobulin G antibody response and was partially protective (54%) against
      intrahepatic challenge with 5 x 10(5) virulent axenic trophozoites (strain
      HM1:IMSS). In summary, the recombinant form of the E. histolytica 29-kDa antigen
      demonstrated serologic specificity for amebic liver abscess, exhibited conserved
      T-cell epitopes, and was effective as a subunit vaccine in an experimental animal
      model of amebic liver abscess.

PMID- 7822013
TI  - Pathogenicity of Saccharomyces cerevisiae in complement factor five-deficient
      mice.
AB  - We have previously determined the relative virulence of isolates of Saccharomyces
      cerevisiae on the basis of differences in proliferation and resistance to
      clearance in CD-1 mice. These infections were not fatal. To further characterize
      S. cerevisiae pathogenesis, we studied a virulent clinical isolate, YJM128, and
      an avirulent nonclinical isolate, Y55, in C5-deficient mice. DBA/2N mice were
      infected intravenously with YJM128 or Y55, and temporal burdens of yeast cells in
      various organs were determined. After infection with 10(7) CFU, Y55 increased by
      13-fold and YJM128 increased by 20-fold in the brain from day 0 to 3. In
      addition, YJM128 increased by 4-fold in the kidneys, whereas Y55 decreased by 16
      fold. Both isolates declined in number in other organs. In all studies, 90% of
      mice infected with 10(7) CFU of YJM128 died between days 2 and 7, whereas no mice
      infected with equivalent numbers of Y55 died. No mice died after infection with
      10(6) CFU of Y55 or YJM128. The importance of C5 was confirmed by studies using
      B10.D2/oSnJ (C5-) mice and their congenic C5+ counterparts. Again, the C5- mice
      were most susceptible to infection with S. cerevisiae, with 63% infected with
      YJM128 dying by day 7; no C5+ mice died. No Y55-infected mice died, and mean
      burdens in the brain at day 14 were sevenfold lower in C5+ mice than in C5- mice.
      Seven of 10 other S. cerevisiae isolates were also more virulent in DBA/2N than
      CD-1 mice, causing > or = 40% mortality. These data indicate that C5 is a
      critical factor in host resistance against S. cerevisiae infections and further
      confirm the pathogenic potential of some isolates of S. cerevisiae.

PMID- 7822014
TI  - Characterization of an insect cell-derived Theileria parva sporozoite vaccine
      antigen and immunogenicity in cattle.
AB  - Previous data showed that six out of a group of nine cattle inoculated with NS1
      p67, a recombinant form of a 67-kDa Theileria parva sporozoite surface protein,
      were immune to East Coast fever. This bacterially expressed antigen encoded all
      709 amino acid residues of p67 fused to the C-terminal end of 87 residues derived
      from NS1, a structural protein of influenza virus, and a linker DNA sequence. NS1
      p67 lacked reactivity with TpM 12, a monoclonal antibody to native p67, and had
      an estimated molecular mass of 110 kDa, as opposed to the calculated mass of
      85,000 Da. We have used the baculovirus expression system in an attempt to
      express this parasite protein in a native form and thereby increase the
      protective capacity of the antigen. However, Spodoptera frugiperda SF21AE cells
      infected with recombinant virus expressed p67 as a 100-kDa molecule. The host
      cells exhibited a limited capacity to glycosylate this molecule to a 110-kDa
      form, and p67 was not exported to the surface membrane. TpM 12 did not bind to
      these recombinant forms but, at time points late during viral infection, reacted
      with a molecule of about 70 kDa. Since the bulk of insect cell-derived p67 was
      not expressed in an appropriate form, we tested the immunogenicity of these
      partially processed recombinant p67 forms in cattle. Two groups of three cattle
      were inoculated with antigen formulated either with saponin or Freund's adjuvant.
      As seen previously with NS1-p67, all animals developed high levels of anti-p67
      antibodies that neutralized sporozoite infectivity in vitro, but antigen-specific
      T-cell proliferative responses were not detected in peripheral blood. Given the
      caveat of the small number of cattle analyzed, insect cell-derived p67 does not
      appear to be superior to NS1-p67 as an immunogen, and the latter remains the
      molecule of choice for the development of vaccines against East Coast fever.

PMID- 7822015
TI  - A mutation at histidine residue 135 of toxic shock syndrome toxin yields an
      immunogenic protein with minimal toxicity.
AB  - Structure-function studies have revealed that the region between amino acids 115
      and 141 of toxic shock syndrome toxin 1 (TSST-1) constitutes a biologically
      active domain. A critical residue appears to be histidine 135, since a site
      directed mutation that alters the histidine to alanine (H135A) results in a loss
      of mitogenic activity and an absence of toxicity as measured in a rabbit
      infection model of toxic shock syndrome. We have characterized the mutant toxin
      further and report here on its immunogenic activity in rabbits and on the
      protective ability of mutant-specific antibodies in two animal models of toxin
      mediated shock. Antibodies raised in rabbits by immunization with the purified
      H135A are fully cross-reactive with staphylococcal TSST-1 and wild-type
      recombinant TSST-1 (rTSST-1) expressed in Escherichia coli. The H135A antibodies
      neutralized the mitogenic activity for murine splenic T cells equally well as did
      TSST-1-specific polyclonal and monoclonal antibodies. In addition, the H135A
      antibodies blocked the production of tumor necrosis factor by spleen cells
      stimulated with rTSST-1. The toxicities of rTSST-1 and H135A were compared in D
      galactosamine (D-GalNH2)-sensitized MRL-lpr/lpr mice. The nontoxicity of H135A
      was confirmed in this murine model of superantigen-induced septic shock. No
      toxicity of H135A was demonstrable at doses of 60 micrograms, while doses of
      rTSST-1 as low as 2 micrograms caused significant mortality within 24 to 72 h
      after challenge. Furthermore, subsequent to challenge of mice with H135A, no
      elevation in the serum levels of interleukin-2 or tumor necrosis factor was
      measurable. Passive immunization with H135A antibodies also protected MRL-lpr/lpr
      mice against lethal challenge with rTSST-1. Finally, rabbits actively immunized
      with purified H135A did not succumb to infection with a transformed strain of
      Staphylococcus aureus expressing rTSST-1. Additional animal studies will be
      required to confirm the immunizing potential of H135A and the efficacy of H135A
      antibodies as a neutralizing antitoxin.

PMID- 7822016
TI  - Role of CD8 T cells in primary Chlamydia infection.
AB  - The role of CD4 and CD8 T cells in primary Chlamydia trachomatis pneumonia was
      investigated by using in vivo depletion techniques to eliminate T-cell
      populations. Reduction of either CD4 T cells or CD8 T cells caused a significant
      increase in organism burden in the lungs, as measured by both quantitative
      culture and detection of chlamydial antigen on day 14 postinfection. Chlamydia
      specific antibody levels in plasma or antigen-induced gamma interferon (IFN
      gamma) production by spleen cells was dramatically reduced by depletion of CD4
      cells. The reduction in IFN-gamma achieved by depletion of CD8 cells did not
      reach statistical significance. In the survival studies, depletion of CD4 cells
      led to a significant increase in mortality. Although there was a trend toward
      higher mortality, depletion of CD8 cells did not significantly increase
      mortality. The role of CD8 T cells in host defense was clarified in studies using
      beta 2-microglobulin-deficient (major histocompatibility class I antigen
      deficient, C1D) mice which are defective in CD8 T-cell function. In this model, a
      significant increase in organism burden was seen during infection in C1D mice
      compared with that C57BL/6 controls and a significant increase in mortality was
      observed as well. However, surviving C1D mice were able to clear the infection by
      day 34. C1D mice had increased numbers of CD4 T cells in both the spleen and the
      lungs during infection compared with those of C57BL/6 controls. IFN-gamma in
      C57BL/6 mice was produced by both CD4 and CD8 cells. Thus, there is a protective
      role for both CD4 and CD8 cells in host defense against Chlamydia infection, but
      the former appear to be dominant.

PMID- 7822017
TI  - Human lipopolysaccharide-binding protein potentiates bactericidal activity of
      human bactericidal/permeability-increasing protein.
AB  - Human bactericidal/permeability-increasing protein (BPI) from neutrophils and a
      recombinant amino-terminal fragment, rBPI23, bind to and are cytotoxic for gram
      negative bacteria both in vitro and ex vivo in plasma or whole blood. To function
      in vivo as an extracellular bactericidal agent, rBPI23 must act in the presence
      of the lipopolysaccharide-binding protein (LBP), which also binds to but has no
      reported cytotoxicity for gram-negative bacteria. LBP, which is present at 5 to
      10 micrograms/ml in healthy humans and at much higher levels in septic patients,
      mediates proinflammatory host responses to gram-negative infection. On the basis
      of these previous observations, we have examined the effect of recombinant LBP
      (rLBP) on the bactericidal activity of rBPI23 against Escherichia coli J5 in
      vitro. Physiological concentrations of rLBP (5 to 20 micrograms/ml) had little or
      no bactericidal activity but reduced by up to approximately 10,000-fold the
      concentration of BPI required for bactericidal or related activities in assays
      which measure (i) cell viability as CFUs on solid media or growth in broth
      culture and (ii) protein synthesis following treatment with BPI. LBP also
      potentiated BPI-mediated permeabilization of the E. coli outer membrane to
      actinomycin D by about 100-fold but had no permeabilizing activity of its own.
      Under optimal conditions for potentiation, fewer than 100 BPI molecules were
      required to kill a single E. coli J5 bacterium.

PMID- 7822018
TI  - Response to stimulation with recombinant cytokines and synthesis of cytokines by
      murine intestinal macrophages infected with the Mycobacterium avium complex.
AB  - Current evidence suggests that the gut is the chief portal of entry for organisms
      of the Mycobacterium avium complex (MAC) in AIDS patients. Bacterial invasion of
      intestinal mucosa presumably occurs through epithelial cells, and M cells in the
      Peyer's patches, where the bacteria have contact with immunocompetent cells such
      as macrophages and T and B lymphocytes. As mucosal macrophages are probably the
      first line of defense against MAC, we examined their ability to inhibit
      intracellular growth of MAC when properly stimulated. Mouse intestinal
      macrophages were purified, infected with MAC 101, serovar 1, and MAC 86-2686,
      serovar 16, and subsequently stimulated with recombinant tumor necrosis factor
      alpha (TNF-alpha), gamma interferon (IFN-gamma), granulocyte-macrophage colony
      stimulating factor (GM-CSF), or macrophage colony-stimulating factor (M-CSF).
      Viable intracellular bacteria were quantitated at 24 h after infection and again
      after 4 days of infection. Stimulation with TNF-alpha, IFN-gamma, and GM-CSF, but
      not M-CSF, was associated with mycobacteriostatic and/or mycobactericidal
      activity in macrophages. Treatment with 10(3) U of TNF-alpha, GM-CSF, and IFN
      gamma per ml at 24 h prior to infection with MAC resulted in a significant
      enhancement in killing of MAC at 4 days after infection, compared with that
      observed for macrophages exposed to cytokines after infection. When stimulated
      with lipopolysaccharide or live MAC, intestinal macrophages had produced
      significantly less TNF-alpha and transforming growth factor beta than had splenic
      and peritoneal macrophages, although the levels of production of interleukin 6
      and interleukin 10 among the three populations of cells were similar. Intestinal
      macrophages can be stimulated with cytokines to inhibit the intracellular growth
      of MAC, but they have differentiated abilities to produce cytokines which can
      modulate the anti-MAC immune response.

PMID- 7822019
TI  - Cytokine expression in the liver during the early phase of murine tularemia.
AB  - Cytokine expression was determined in the livers of mice inoculated
      subcutaneously with Francisella tularensis LVS. During the first 48 h of
      infection, there was a logarithmic increase of bacteria in the liver, with a
      doubling time of 2.5 h. Within 48 h, tumor necrosis factor alpha (TNF-alpha),
      interleukin 10 (IL-10), IL-12, and gamma interferon (IFN-gamma) mRNAs were
      expressed, and production of TNF-alpha and IFN-gamma was demonstrated. There was
      no expression within 96 h of mRNA from IL-2, IL-3, or IL-4. After subcutaneous
      inoculation of heat-killed LVS, no expression of any of the cytokine mRNAs and no
      increase in the levels of TNF-alpha or IFN-gamma occurred. The expression of TNF
      alpha, IL-12, and IFN-gamma is held to be important to evoke an early T-cell
      independent host defense against F. tularensis as well as to drive the expansion
      of a protective Th1 cell response.

PMID- 7822020
TI  - Mice immunized by primary vaginal Candida albicans infection develop acquired
      vaginal mucosal immunity.
AB  - It has been postulated that systemic cell-mediated immunity (CMI) is an important
      host defense mechanism against Candida infections of the vagina. However, in an
      estrogen-dependent murine model of experimental vaginal candidiasis, we recently
      showed that systemic Candida-specific Th1-type CMI induced by immunization with
      Candida culture filtrate antigen had no effect on vaginal Candida population
      levels during the course of a vaginal infection. In the present study, mice given
      a second vaginal inoculation in the presence of peripheral Candida-specific Th1
      type CMI induced by prior vaginal infection had anamnestic-type increased delayed
      type hypersensitivity (DTH) responses, concomitant with significantly fewer
      Candida organisms in the vagina than in primary-infected mice. In addition,
      organisms in secondary-infected mice were fragmented and superficial penetration
      into the epithelium was reduced. The systemic presence of Candida-specific T
      suppressor (Ts) cells that significantly suppressed the infection-derived
      anamnestic DTH reactivity did not abrogate the protective effect in the vagina.
      Additional experiments showed that vaginally immunized mice were not protected
      from gastrointestinal or systemic candidiasis and, in contrast to mice with a
      second vaginal infection, did not demonstrate anamnestic DTH reactivity. These
      results suggest that a moderate level of local protection against a Candida
      vaginal infection can be achieved by vaginal immunization but that the protective
      role of acquired peripheral Candida-specific Th1-type reactivity at the vaginal
      mucosa appears to be limited.

PMID- 7822021
TI  - Induction of opsonizing antibodies after injection of recombinant Plasmodium
      falciparum vaccine candidate antigens in preimmune Saimiri sciureus monkeys.
AB  - We have previously shown that Plasmodium falciparum recombinant antigens PfEB200,
      R23, and Pfi72 inhibit opsonization of infected erythrocytes by hyperimmune
      Saimiri sera, indicating that they contain target epitopes involved in the
      phagocytosis of infected erythrocytes. We have investigated in this study the
      immune response of Saimiri monkeys with previous experience of malaria infections
      (preimmune monkeys) after injection of these recombinant antigens, administered
      alone or simultaneously. The humoral response to the recombinant antigens was
      monitored by radioimmunoassay, and the response to P. falciparum blood stages was
      assayed by immunofluorescence. The relative proportion of protective versus
      nonprotective immunoglobulin subtypes was investigated by using 3A2/G6 and 3E4/H8
      monoclonal antibodies, and the capacity of the antisera to promote in vitro
      phagocytosis of infected erythrocytes was evaluated. The antigens evoked in most
      cases a secondary-type antibody response, resulting in important increases in
      antigen-specific antibody titers and concomitantly in anti-P. falciparum titers.
      The ratio of 3A2/G6 to 3E4/H8 immunoglobulin subtypes varied with the immunogen
      used. Opsonizing antibodies were boosted in several animals, the most promising
      combination being the mixture of PfEB200 and R23 that induced long-lasting
      production in five of five animals. The detectable opsonizing activity appearing
      after immunization of the animals was antigen specific, as it was lost after
      adsorption of the recombinant antigens. The challenge of the animals with blood
      stage parasites confirmed previous findings showing a correlation between the
      presence of detectable opsonizing antibodies in serum and protection.

PMID- 7822022
TI  - Immunization with live recombinant Salmonella typhimurium aroA producing F1
      antigen protects against plague.
AB  - An attenuated Salmonella typhimurium strain which expressed the F1 capsular
      antigen of Yersinia pestis was constructed by transformation of S. typhimurium
      SL3261 with plasmid pFGAL2a, a derivative of pUC18 which contained the caf1 gene
      without the leader sequence. The recombinant was used to vaccinate mice
      intragastrically and intravenously. The immunity induced was able to protect mice
      against challenge with a virulent strain of plague. Protection correlated with
      the induction of high titers of immunoglobulin G in serum samples and a specific
      T-cell response.

PMID- 7822023
TI  - Adherence of Candida albicans to human buccal epithelial cells: host-induced
      protein synthesis and signaling events.
AB  - The synthesis of proteins by Candida albicans was studied following adherence of
      blastoconidia to human buccal epithelial cells (HBEC). Initially, labeling of
      HBEC, C. albicans, and HBEC-C. albicans with [35S]methionine was performed. After
      a 3-h incubation and prior to labeling with [35S]methionine, the cultures were
      treated with cycloheximide to prevent HBEC protein synthesis. The HBEC-C.
      albicans mixture as well as C. albicans and HBEC incubated separately were
      extracted with beta-mercaptoethanol (beta-ME). These extracts as well as the cell
      residue (solubilized by boiling with sodium dodecyl sulfate [SDS]) were examined
      by SDS-polyacrylamide gel electrophoresis and autoradiography. In comparison to
      cultures of C. albicans incubated without HBEC, proteins with molecular masses of
      approximately 52 to 56 kDa from beta-ME extracts and from SDS-solubilized cells
      were observed only from adhering cultures. In addition, unlabeled beta-ME
      extracts were electrotransferred to nitrocellulose and immunoblotted with
      antiphosphotyrosine antibodies to determine whether cell signaling events were
      occurring during adherence. Proteins with molecular masses of 54 and 60 kDa were
      recognized only in mixed cultures of C. albicans and HBEC. These data indicate
      that following adherence of C. albicans to HBEC, new Candida proteins are
      expressed. Further, these events are accompanied by the expression of signal
      proteins, presumably of Candida origin.

PMID- 7822024
TI  - Antibodies to Cryptococcus neoformans glucuronoxylomannan enhance antifungal
      activity of murine macrophages.
AB  - Monoclonal antibodies (MAbs) to the capsular polysaccharide of the pathogenic
      fungus Cryptococcus neoformans can prolong survival and decrease organ fungal
      burden in experimental murine cryptococcosis. To investigate the mechanism of
      antibody-mediated protection, the interaction of C. neoformans and murine
      macrophage-like J774.16 cells was studied in the presence and absence of MAbs
      differing in isotype. Immunoglobulin G2a (IgG2a) and IgG2b isotype switch
      variants were isolated from an IgM hybridoma to complete the IgG subclass set.
      IgM, IgG1, IgG2a, IgG2b, IgG3, and IgA MAbs were studied for their ability to
      promote phagocytosis and reduce the number of CFU in C. neoformans and J774.16
      cell cocultures. The MAbs in this set had similar if not identical fine
      specificities and were derived from a single B cell. All isotypes promoted
      phagocytosis; however, the IgG subclasses were more effective opsonins than IgM
      or IgA. All isotypes enhanced J774.16 anti-C. neoformans activity in vitro, as
      measured by a reduction in the number of CFU. The IgG1 MAbs were consistently
      more active in promoting opsonization and reducing the number of CFU. Addition of
      IgG1 MAb to C. neoformans and J774.16 cocultures resulted in rapid reduction in
      the number of CFU, which is consistent with fungal killing. Electron microscopy
      revealed that MAb-opsonized C. neoformans cells were internalized and appeared
      damaged. Administration of IgM, IgG1, IgG2a, and IgG2b isotype switch variant
      MAbs revealed that the IgG2a and IgG2b subclasses were the most and least
      effective isotypes, respectively, in prolonging survival in an intraperitoneal
      murine infection model. The results indicate that murine antibody subclasses
      differ in their ability to enhance macrophage anti-C. neoformans activity and
      suggest that antibody enhancement of macrophage function is a mechanism by which
      antibodies modify infection in vivo.

PMID- 7822025
TI  - Antigenic and structural similarities between Mycobacterium tuberculosis 50- to
      55-kilodalton and Mycobacterium bovis BCG 45- to 47-kilodalton antigens.
AB  - The relationship between Mycobacterium tuberculosis 50- to 55-kDa protein and
      Mycobacterium bovis BCG 45- to 47-kDa antigen was examined by using immunological
      and biochemical criteria. Reciprocal cross-reactivity with a rabbit polyclonal
      antiserum against the M. bovis BCG protein and with a monoclonal antibody raised
      against the M. tuberculosis antigen was observed. The epitope recognized by this
      antibody was apparently present only in proteins of M. tuberculosis and M. bovis
      BCG among the 11 mycobacterial species tested. The amino-terminal sequences and
      total amino acid contents of these proteins showed strong similarities. Both
      antigens are glycoproteins as assessed by binding of concanavalin A, labeling of
      carbohydrate moieties with biotin-hydrazide, and digestion of carbohydrates with
      jack bean alpha-D-mannosidase, which produced a reduction of the molecular
      weights of the proteins and totally eliminated concanavalin A binding. Both M.
      tuberculosis and M. bovis BCG proteins are secreted, since they were found mainly
      in the culture medium. Analysis of M. tuberculosis 50- to 55-kDa antigen by two
      dimensional gel electrophoresis showed at least seven different components, as
      previously described for the M. bovis BCG antigen. Solid-phase immunoassays
      showed that the purified M. tuberculosis 50- to 55-kDa protein was recognized by
      serum specimens from 70% of individuals with pulmonary tuberculosis from a total
      of 77 Mexican patients examined.

PMID- 7822026
TI  - Use of adhesion-defective mutants of Staphylococcus aureus to define the role of
      specific plasma proteins in promoting bacterial adhesion to canine arteriovenous
      shunts.
AB  - We used an ex vivo canine arteriovenous shunt model, previously developed to
      study plasma protein adsorption and thrombogenesis on polymeric biomaterials, to
      define the role of host proteins in promoting adhesion of Staphylococcus aureus.
      Either polyethylene or polyvinyl chloride tubings were exposed to canine blood
      for 5, 15, or 60 min at a flow rate of 300 ml/min and then were flushed in
      phosphate-buffered saline (PBS), cut into 1.5-cm segments, and stored at -70
      degrees C. After thawing, each segment was preincubated in 0.5% albumin in PBS to
      prevent nonspecific staphylococcal attachment to surfaces that were not exposed
      to blood. Each segment was then incubated with 4 x 10(6) CFU of [3H]thymidine
      labelled S. aureus per ml for 60 min at 37 degrees C in an in vitro adhesion
      assay. Two site-specific mutants of S. aureus were tested: one specifically
      defective in adhesion to surface-bound fibronectin (FnAd-def) and the other
      defective in adhesion to fibrinogen (FgAD-def) [corrected]. Compared with their
      respective parental strains, the FgAd-def, but not the FnAd-def, mutant of S.
      aureus showed a strong (> 80%) decrease in attachment to ex vivo tubings. The
      adhesion of each strain of S. aureus onto polyethylene was consistently more than
      twofold higher than the adhesion onto polyvinyl chloride segments exposed to
      flowing blood for 5 or 15 min, but adhesion became similar to that on polyvinyl
      chloride after 60 min of exposure. In conclusion, the specific adhesion-defective
      mutants of S. aureus suggested that fibrinogen was the most active adhesion
      promoting protein in a short-term blood-material interaction. The experimental
      approach described in this study should prove useful for screening materials
      thought to be resistant to protein-mediated staphylococcal adhesion and
      colonization.

PMID- 7822027
TI  - High tumor necrosis factor alpha (TNF-alpha) production in Trypanosoma cruzi
      infected pregnant mice and increased TNF-alpha gene transcription in their
      offspring.
AB  - Since tumor necrosis factor alpha (TNF-alpha) is known to be involved in the feto
      maternal relationship, this cytokine was studied in Trypanosoma cruzi-infected
      pregnant BALB/c mice and their fetuses and offspring. Pregnant chronically
      infected mice displayed significantly higher levels of circulating TNF-alpha than
      animals either only infected or only pregnant. TNF-alpha was undetectable in sera
      of uninfected and nonpregnant mice as well as in breast milk obtained from
      infected and uninfected animals. Fetuses from infected mice exhibited
      significantly more cells containing TNF-alpha mRNA in their thymus than fetuses
      from uninfected mothers. When infected 2 months after birth, offspring born to
      infected and uninfected mothers displayed similar amounts of circulating TNF
      alpha during chronic infection, whereas this cytokine was only weakly detectable
      during the acute phase of the disease. An intravenous injection of
      lipopolysaccharide during acute infection strongly increased the production of
      TNF-alpha in offspring born to infected mothers to levels higher than those in
      progeny from uninfected mice. These results suggest that TNF-alpha is an
      important cytokine in the feto-maternal relationship during T. cruzi infection
      and that fetuses and offspring of infected mothers are primed to produce elevated
      levels of TNF-alpha.

PMID- 7822028
TI  - Humoral and cell-mediated immunity to the Plasmodium falciparum ring-infected
      erythrocyte surface antigen in an adult population exposed to highly endemic
      malaria.
AB  - A parasitological and immunological survey was carried out in an area in Papua
      New Guinea highly endemic for malaria. Two hundred fourteen adult individuals
      were selected for studies to assess their immune responses against the malaria
      vaccine candidate ring-infected erythrocyte surface antigen (RESA). Total
      immunoglobulin G (IgG) antibodies directed against RESA as well as specific IgG1,
      IgG2, and IgG3 antibodies were determined. Humoral responses directed against
      RESA were frequent in all IgG subclasses. Only IgG3 responses were found to be
      age dependent. Total anti-RESA IgG antibodies were not correlated with protection
      against malaria as measured by parasite prevalence, parasite density, or health
      center attendance. In contrast, cytophilic antibodies (IgG1 and IgG3) were
      associated with reduced Plasmodium falciparum prevalence and reduced health
      center attendance. T-cell proliferation in general was low and very infrequent.
      No correlation between humoral and cellular immune responses could be found.
      Parasite density, parasite prevalence, and health center visits tended to be
      reduced in individuals with good humoral and cell-mediated immune responses.

PMID- 7822029
TI  - Differential expression of interferon regulatory factor 1 (IRF-1), IRF-2, and
      interferon consensus sequence binding protein genes in lipopolysaccharide (LPS)
      responsive and LPS-hyporesponsive macrophages.
AB  - Macrophages secrete interferon (IFN), as well as other cytokines, following
      lipopolysaccharide (LPS) stimulation. The interferon regulatory factors (IRFs)
      comprise a family of DNA-binding proteins that have been implicated in the
      transcriptional regulation of IFN and certain IFN-inducible genes. We therefore
      characterized basal and LPS-inducible levels of IRF-1, IRF-2, and interferon
      consensus sequence binding protein (ICSBP) mRNA in LPS-responsive macrophages and
      compared the expression of these genes in macrophages that typify two murine
      models of LPS hyporesponsiveness. In the first model, the LPS-hyporesponsive
      phenotype of the C3H/HeJ mouse is genetically determined and maps to the Lps
      locus on mouse chromosome 4. In the second model, normally LPS-responsive
      macrophages acquire a transient LPS-hyporesponsive phenotype following a prior
      exposure to LPS, a phenomenon referred to as "endotoxin tolerance." Using reverse
      transcription PCR, we detected basal levels of IRF-1 mRNA in LPS-responsive
      (Lpsn) macrophages that were approximately 15 times higher than those found in
      LPS-hyporesponsive (Lpsd) macrophages. Conversely, Lpsd macrophages expressed
      basal levels of IRF-2 mRNA that were approximately 18 times higher than those
      expressed in Lpsn macrophages. LPS stimulation resulted in a dose- and time
      dependent accumulation of IRF-1, IRF-2, and ICSBP mRNA only in Lpsn macrophages.
      Cycloheximide inhibited the accumulation of LPS-stimulated IRF-2 and ICSBP mRNA,
      but not IRF-1 mRNA, thus designating IRF-1 an immediate-early, LPS-inducible
      gene. Finally, macrophages rendered tolerant to endotoxin expressed elevated but
      nonmaximal mRNA levels for all three transcription factors that are not reinduced
      upon secondary challenge with LPS. Thus, the IRFs may represent yet an additional
      molecular pathway in the complex response to LPS.

PMID- 7822030
TI  - Streptococcus salivarius ATCC 25975 possesses at least two genes coding for
      primer-independent glucosyltransferases.
AB  - Fractionation of the culture medium showed that Streptococcus salivarius ATCC
      25975 secreted a glucosyltransferase (Gtf) that was primer independent. On the
      basis of this observation, a gene library of S. salivarius chromosomal DNA cloned
      into lambda L47.1 was screened for a gene(s) coding for such an activity. As a
      result of this screening process, two new gtf genes, gtfL and gtfM, both of which
      coded for primer-independent Gtf activities, were isolated. GtfL produced an
      insoluble glucan that was refractory to digestion by the endo-(1-->6)-alpha-D
      glucanase. of Chaetonium gracile, while GtfM produced a soluble glucan that was
      readily degraded by the glucanase. Comparison of the deduced amino acid sequences
      of gtfL and gtfM with 10 other available Gtf sequences allowed the relatedness of
      the conserved catalytic regions to be assessed. This analysis showed that the 12
      enzymes did not form clusters based on their primer dependencies or on their
      product solubilities. Further analysis of the YG repeats in the C-terminal glucan
      binding domains of GtfJ, GtfK, GtfL, and GtfM from S. salivarius showed that
      there was strong homology between a block of contiguous triplet YG repeats
      present in the four alleles. These blocks of YG repeats were coded for by a
      region of each gene that appeared to have arisen as a result of a recent
      duplication event(s).

PMID- 7822031
TI  - DNA sequence of the serum opacity factor of group A streptococci: identification
      of a fibronectin-binding repeat domain.
AB  - The serum opacity factor (SOF) is a group A streptococcal protein that induces
      opacity of mammalian serum. The serum opacity factor 22 gene (sof22) from an M
      type 22 strain was cloned from an EMBL4 library by screening for plaques
      exhibiting serum opacity activity. DNA sequencing yielded an open reading frame
      of 3,075 bp. Its deduced amino acid sequence predicts a protein of 1,025 residues
      with a molecular weight of 112,735, a size that approximates that of the SOF22
      protein isolated from both the original streptococcal strain and Escherichia coli
      harboring the cloned sof22 gene. The molecule is composed of three domains: an N
      terminal domain responsible for the opacity reaction (opacity domain), a repeat
      domain with fibronectin-binding (Fn-binding) activity, and a C-terminal cell
      attachment domain. The C-terminal end of SOF22 is characterized by a hexameric
      LPXTGX motif, an adjacent hydrophobic region, and a charged C terminus, which are
      the hallmarks of cell-bound surface proteins found on nearly all gram-positive
      bacteria. Immediately upstream of this cell anchor region, SOF22 contains four
      tandem repeat sequence blocks, flanked by prolinerich segments. The repeats share
      up to 50% identity with a repeated motif found in other group A streptococcal Fn
      binding proteins and exhibit Fn-binding activity, as shown by subcloning
      experiments. According to deletion analysis, the opacity domain is confined to
      the region N terminal to the repeat segment. Thus, SOF22 is unique among the
      known Fn-binding proteins from gram-positive bacteria in containing an
      independent module with a defined function in its N-terminal portion. Southern
      blot analysis with a probe from this N-terminal region indicates that the opacity
      domain of SOF varies extensively among different SOF-producing M types.

PMID- 7822032
TI  - Extracellular virulence factors in Bacillus cereus endophthalmitis: methods and
      implication of involvement of hemolysin BL.
AB  - Bacillus cereus is a common cause of highly fulminant posttraumatic and
      metastatic endophthalmitis. Exotoxins or enzymes likely contribute to the
      severity of the infection, but specific virulence factors have not been
      identified. We developed two methods for the identification of B. cereus ocular
      virulence factors. In an in vitro assay that allows screening of multiple
      samples, retinal toxicity was estimated by measuring the release of lactate
      dehydrogenase from retinal buttons treated with B. cereus toxins. The results
      from this assay were confirmed with a sterile endophthalmitis model in which the
      histopathologic effect of intravitreally injected toxins was assessed. We tested
      pure hemolysin BL (HBL), a tripartite dermonecrotic vascular permeability factor
      of B. cereus, and crude exotoxin (CET) preparations, consisting of concentrated,
      cell-free B. cereus culture supernatant. In the in vitro assay, both CET and HBL
      caused rapid release of lactate dehydrogenase and retinal disintegration. In
      vivo, the toxins caused endophthalmitis clinically characteristic of B. cereus
      within 4 h. Histological changes included rapid retinal necrosis and detachment,
      choroidal edema, detachment and disruption of the retinal pigment epithelium, and
      rapid infiltration of polymorphonuclear leukocytes. Neutralization of HBL in CET
      preparations inhibited toxicity in vitro by 54%, and pure HBL was less toxic than
      CET with equal HBL contents in both methods. The results suggest that B. cereus
      ocular virulence is multifactorial and that HBL contributes to virulence.

PMID- 7822033
TI  - Binding of the fibrillar CS3 adhesin of enterotoxigenic Escherichia coli to
      rabbit intestinal glycoproteins is competitively prevented by GalNAc beta 1-4Gal
      containing glycoconjugates.
AB  - We have attempted to characterize the binding specificity of the coli surface 3
      (CS3) subcomponent of colonization factor antigen II of enterotoxigenic
      Escherichia coli, by means of an immunoblot method in which the binding of
      fimbriated bacteria to sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      separated rabbit intestinal cell membranes was evaluated. Isolated CS3 fibrillae
      as well as bacteria expressing CS3 on their surface bound to several intestinal
      cell membrane structures, i.e., structures present in the electrophoretic front
      and in the 30- to 35-kDa range and, most prominently, 120- to 140-kDa structures.
      Delipidization and protein digestion of the rabbit brush borders revealed that
      CS3 bound to structures of a proteinaceous nature. Sodium meta-periodate
      oxidation of the intestinal cell membranes abolished all their CS3 binding
      activity, indicating that CS3 bound to carbohydrate moieties of glycoproteins.
      The binding of CS3 to the separated intestinal proteins could also be inhibited
      by preincubation with the lectin derived from Maackia amurensis, indicating that
      CS3 bound to galactoproteins in the rabbit intestine. Inhibition experiments
      using equimolar amounts of various gangliosides demonstrated that GM1, asialo
      GM1, and GM2 inhibited the binding of CS3 equally well, whereas GM3 was not as
      effective. These results suggested that the critical CS3 binding epitope
      consisted of the carbohydrate sequence GalNAc beta 1-4Gal. This was supported by
      electron microscopic experiments showing that this disaccharide, O linked to
      bovine serum albumin via a spacer, localized around CS3-positive bacteria but not
      at all around corresponding CS3-negative mutants. Furthermore, CS3-expressing
      bacteria recognized this neoglycoprotein when it was immobilized on
      nitrocellulose. The GalNAc beta 1-4Gal disaccharide has also been implicated as a
      binding structure for other pathogenic bacteria such as enteropathogenic E. coli
      and Pseudomonas aeruginosa.

PMID- 7822034
TI  - Cultivation of Ehrlichia chaffeensis in mouse embryo, Vero, BGM, and L929 cells
      and study of Ehrlichia-induced cytopathic effect and plaque formation.
AB  - We successfully propagated Ehrlichia chaffeensis in mouse embryo, Vero, BGM, and
      L929 cells inoculated with host cell-free ehrlichiae, indicating that E.
      chaffeensis is capable of entry, survival, and growth in a relatively wide range
      of cell types derived from different species. We demonstrated rapid adaptation of
      E. chaffeensis in these cell lines, so that typical morulae could be detected as
      early as 5 days after inoculation. E. chaffeensis-induced cytopathic effect with
      different morphological characteristics in mouse embryo, Vero, and L929 cells.
      The earliest cytopathic effect appeared in untreated and irradiated mouse embryo
      cells at 4 days postinoculation. As the infected foci gradually expanded, the
      center of the foci showed necrotic cells with pyknotic nuclei and degraded
      morulae. E. chaffeensis caused cell lysis in untreated and irradiated L929 cells,
      with formation of distinct, round macroscopic plaques at 18 days postinoculation.
      In untreated and irradiated Vero cells, E. chaffeensis produced infected foci
      composed of loosely interwoven necrotic cells, spaces of detached cells, cells
      filled with morulae, and uninfected cells, resulting in characteristic reticular
      foci. Irradiated cells generally contained many large morulae and presented
      larger cytopathic foci. DH82 and BGM cells did not develop obvious cytopathic
      foci under the conditions employed. The findings reported herein offer the
      opportunity to study the pathogenic mechanism of cell injury by E. chaffeensis,
      the basis for quantification of infectious E. chaffeensis, improved approaches
      for recovery of ehrlichiae from human patients and tick hosts, and additional
      methods for cultivation of E. chaffeensis for molecular analysis.

PMID- 7822035
TI  - Lipopolysaccharides of Actinobacillus pleuropneumoniae bind pig hemoglobin.
AB  - A previous study indicated that lipopolysaccharides (LPS) extracted from
      Actinobacillus pleuropneumoniae bind two low-molecular-mass proteins, of
      approximately 10 and 11 kDa, present in porcine respiratory tract secretions (M.
      Belanger, D. Dubreuil, and M. Jacques, Infect. Immun. 62:868-873, 1994). In the
      present study, we determined the N-terminal amino acid sequences of these two
      proteins, which revealed high homology with the alpha and beta chains of pig
      hemoglobin. Some isolates of A. pleuropneumoniae were able to use hemoglobin from
      various animal species as well as other heme compounds as sole sources of iron
      for growth, while other isolates were unable to use them. Immunoelectron
      microscopy showed binding of pig hemoglobin at the surface of all A.
      pleuropneumoniae isolates as well as labeling of outer membrane blebs. We
      observed, using Western blotting (immunoblotting), that the lipid A-core region
      of LPS of all isolates was binding pig hemoglobin. Furthermore, lipid A obtained
      after acid hydrolysis of LPS extracted from A. pleuropneumoniae was able to bind
      pig hemoglobin and this binding was completely abolished by preincubation of
      lipid A with polymyxin B but was not inhibited by preincubation with
      glucosamines. Fatty acids constituting the lipid A of A. pleuropneumoniae,
      namely, dodecanoic acid, tetradecanoic acid, 3-hydroxytetradecanoic acid,
      hexadecanoic acid, and octadecanoic acid, were also binding pig hemoglobin. Our
      results indicate that LPS of all A. pleuropneumoniae isolates tested bind pig
      hemoglobin and that lipid A is involved in this binding. Our results also
      indicate that some A. pleuropneumoniae isolates are, in addition, able to use
      hemoglobin for growth. Binding of hemoglobin to LPS might represent an important
      means by which A. pleuropneumoniae acquires iron in vivo from hemoglobin released
      from erythrocytes lysed by the action of its hemolysins.

PMID- 7822036
TI  - Involvement of bactericidal factors from thrombin-stimulated platelets in
      clearance of adherent viridans streptococci in experimental infective
      endocarditis.
AB  - Platelets activated with thrombin release bactericidal factors. We studied the
      role of the susceptibility of viridans streptococci to these bactericidal factors
      in the development of infective endocarditis (IE). By using the experimental
      endocarditis rabbit model, the initial adherence and the development of IE were
      assessed for 10 viridans streptococcal strains differing in their
      susceptibilities to releasate (material released) from thrombin-activated
      platelets. Six strains were susceptible and four strains were resistant to these
      releasates. The numbers of vegetations (VGs) colonized at 5 min and 48 h after
      intravenous challenge with 10(4) CFU were determined. At 5 min after challenge,
      significantly more VGs were colonized with bacteria of the six platelet releasate
      susceptible strains than with bacteria of the four releasate-resistant strains (P
      < 0.005). In the releasate-susceptible group of strains, the number of colonized
      VGs decreased significantly between 5 min and 48 h after intravenous inoculation
      (P < 0.001). Such a decrease was not observed with the releasate-resistant
      strains. As a result, the final developments of IE due to releasate-susceptible
      and -resistant strains were not significantly different. The releasate
      susceptible strain 1 and the releasate-resistant strain 2 were selected for more
      detailed experiments. Rabbits were killed at 5 and 30 min and 2, 4, and 48 h
      after inoculation. The number of culture-positive VGs as well as the number of
      adherent bacteria on the individual VGs were determined. The 90% infective dose
      for each strain was 10(5) CFU. At low inoculum concentrations (10(3) and 10(4)
      CFU) a larger proportion of the inoculated bacteria of both strains was found to
      be adherent on VGs than at higher challenge doses. The number of culture-positive
      VGs as well as the number of adherent bacteria per VG decreased rapidly in the
      first 30 min after challenge with strain 1 but not after challenge with strain 2.
      Additional experiments with the platelet releasate-susceptible strain S224 and
      the platelet releasate-resistant stain S182 confirmed the data obtained with
      strains 1 and 2 and indicated that releasate-susceptible strains disappeared from
      the VGs with time, whereas releasate-susceptible strains persisted. In vitro
      studies with VGs excised 5 min after challenge with stain 1 or 2 showed that
      clearance of the releasate-susceptible strain 1 was not caused by complement
      bactericidal activity or surface phagocytosis by polymorphonuclear cells.
      Bacterial cells of strain 1 adherent on excised VTGs were rapidly cleared by
      exposure to fresh clotting blood or to releasates from thrombin-stimulated
      platelet suspension.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7822037
TI  - Relationship of secretion pattern and MPB70 homology with osteoblast-specific
      factor 2 to osteitis following Mycobacterium bovis BCG vaccination.
AB  - Significant homology was found between MPB70 and each of four repeat domains of
      osteoblast-specific factor 2 (OSF-2). Two internal homology regions within each
      repeat domain of OSF-2 presumed to be related to the active site(s) of this bone
      adhesion molecule showed the highest homology. A literature search concerning
      osteitis after Mycobacterium bovis BCG vaccination in neonates revealed that
      MPB70-high-producer substrains were associated with an increased incidence of
      osteitis following vaccination. These observations indicate that the function of
      MPB70 is related to the interaction between bacilli and the host following
      vaccination or infection with mycobacteria.

PMID- 7822038
TI  - Identification of the Chlamydia trachomatis RecA-encoding gene.
AB  - DNA sequencing of the major outer membrane protein (MOMP) gene (omp1) from
      Chlamydia trachomatis shows that some strains have a mosaic structure suggestive
      of homologous recombination between two distinct omp1 genes. On the basis of this
      conjecture, we attempted to clone by complementation and sequence the chlamydial
      recA homolog from C. trachomatis serovar L2. Chlamydial genomic DNA was partially
      restricted with XbaI, and fragments of 2 to 4 kb were ligated into pUC19. The
      recombinant plasmid was electroporated into Escherichia coli HB101 (RecA-), and
      colonies were selected in the presence of methyl methanesulfonate (MMS). A 2.1-kb
      fragment of C. trachomatis DNA in pUC19 conferred relative MMS resistance to E.
      coli HB101. When this recombinant plasmid (pX203) was electroporated into E. coli
      JC14604 (RecA- lacZ), lac+ recombinants were isolated. Rabbit polyclonal
      antibodies produced to purified E. coli RecA were immunoreactive in an immunoblot
      assay with a 35-kDa antigen in RecA- strains of E. coli transformed with pX203.
      The 2.1-kb insert was cycle sequenced by the dideoxy chain termination method. An
      open reading frame of 1,056 bp encoding 352 amino acids that had 44% sequence
      identity with E. coli RecA was identified. The finding of a recA homolog in C.
      trachomatis suggests that homologous recombination may occur in this organism.
      The cloned C. trachomatis RecA-encoding gene will be useful for the construction
      of a recA mutant once a gene transfer system is developed for chlamydiae.

PMID- 7822039
TI  - Inhibition of the Fc receptor-mediated oxidative burst in macrophages by the
      Yersinia pseudotuberculosis tyrosine phosphatase.
AB  - Suppression of host-cell-mediated immunity is a hallmark feature of Yersinia
      pseudotuberculosis infection. To better understand this process, the interaction
      of Y. pseudotuberculosis with macrophages and the effect of the virulence plasmid
      encoded Yersinia tyrosine phosphatase (YopH) on the oxidative burst was analyzed
      in a chemiluminescence assay. An oxidative burst was generated upon infection of
      macrophages with a plasmid-cured strain of Y. pseudotuberculosis opsonized with
      immunoglobulin G antibody. Infection with plasmid-containing Y.
      pseudotuberculosis inhibited the oxidative burst triggered by secondary infection
      with opsonized bacteria. The tyrosine phosphatase activity of YopH was necessary
      for this inhibition. These results indicate that YopH inhibits Fc receptor
      mediated signal transduction in macrophages in a global fashion. In addition,
      bacterial protein synthesis was not required for macrophage inhibition,
      suggesting that YopH export and translocation are controlled at the
      posttranslational level.

PMID- 7822040
TI  - Immunization of rats with the 260-kilodalton Entamoeba histolytica galactose
      inhibitable lectin elicits an intestinal secretory immunoglobulin A response that
      has in vitro adherence-inhibitory activity.
AB  - The 260-kDa galactose-inhibitable lectin of Entamoeba histolytica mediates
      binding of amebic trophozoites to purified colonic mucins and intestinal
      epithelial cells. Parenteral immunization of Lewis rats with immuno-affinity
      purified lectin with Freund's adjuvant and then intra-Peyer's patch inoculation
      of lectin with cholera toxin B subunit as adjuvant elicited a significant anti
      lectin secretory immunoglobulin A response in the bowel lumen. Purified
      intestinal secretory immunoglobulin A from three or four immunized animals
      studied possessed inhibitory activity (P < 0.02) in an in vitro assay of
      trophozoite galactose-specific adherence to Chinese hamster ovary cells.

PMID- 7822041
TI  - Dissociation of endotoxic activities in a chemically synthesized lipid A
      precursor after acetylation.
AB  - In a previous study, a chemically synthesized disaccharide precursor of lipid A
      (406; identical to lipid IVA) was shown to have dramatically reduced lethality, B
      cell mitogenicity, and tumor necrosis factor induction in macrophages when its
      hydroxyl groups were replaced with either succinyl or acetyl residues (K.
      Tanamoto, FEBS Lett. 351:325-329, 1994). Succinylated 406 was found to lose
      Limulus amoebocyte lysate gelation activity completely as a result of the
      modification (about 10(5)-fold), too, as expected. However, acetyl 406,
      surprisingly, exhibited activity comparable to that of the original 406. Both
      succinylated and acetylated 406 lost pyrogenicity completely. These results
      indicate that one of the typical endotoxic activities was dissociated from the
      others and that the ability to induce Limulus amoebocyte lysate gelation is not
      always representative of endotoxin activity.

PMID- 7822042
TI  - Karyotype analysis of virulent Plasmodium falciparum strains propagated in
      Saimiri sciureus: strain adaptation leads to deletion of the RESA gene.
AB  - The squirrel monkey, Saimiri sciureus, is an important experimental model for the
      study of the human malaria parasite Plasmodium falciparum. A detailed karyotype
      analysis of four different P. falciparum strains propagated in S. sciureus was
      done using various subtelomeric antigen gene probes. We observed deletion of the
      complete RESA gene from chromosome 1 in all four strains. Interestingly, a loss
      of RESA was observed immediately upon adaptation to the squirrel monkey,
      suggesting that this DNA rearrangement is fundamental for the P. falciparum
      infection of S. sciureus erythrocytes. However, a RESA-specific gene probe
      hybridized with chromosome 1 of wild isolates from 28 different patients,
      indicating that this gene is maintained during infection of humans.

PMID- 7822043
TI  - The gene encoding protein D (hpd) is highly conserved among Haemophilus
      influenzae type b and nontypeable strains.
AB  - The molecular conservation of a surface-exposed lipoprotein, protein D, of
      Haemophilus influenzae was studied by cloning and sequencing of the gene encoding
      protein D from three encapsulated type b strains and three nontypeable strains of
      H. influenzae. These nucleotide sequences were analyzed with previously reported
      sequences from one type b strain and one nontypeable strain. The nucleotide
      sequences and the deduced amino acid sequences for protein D were highly
      conserved. The deduced amino acid sequence (364 amino acids) of protein D from
      six strains differed only in two amino acids near the C-terminal end. The
      remaining two strains, one type b and one nontypeable, differed from the
      consensus sequence in 7 amino acids each. Protein D is 64 and 36% identical and
      77 and 56% similar to the glycerophosphodiester phosphodiesterases (GlpQ) of
      Escherichia coli and Bacillus subtilis.

PMID- 7822044
TI  - Use of heme and hemoglobin by Escherichia coli O157 and other Shiga-like-toxin
      producing E. coli serogroups.
AB  - The virulence properties of Escherichia coli O157 isolates were compared with
      those of Shiga-like-toxin-producing E. coli of non-O157 serogroups. The growth of
      all E. coli O157 isolates was stimulated by both heme and hemoglobin, and all
      produced enterohemolysin. The incidence of these properties was significantly
      lower in the non-O157 isolates. This may contribute to the greater virulence and
      higher incidence of human infection caused by E. coli O157.

PMID- 7822045
TI  - Cloning of an Enterococcus faecalis endocarditis antigen: homology with adhesins
      from some oral streptococci.
AB  - Serum from a patient with Enterococcus faecalis endocarditis was used to identify
      the gene efaA cloned in Lambda ZapII in Escherichia coli. Nucleotide sequence
      analysis revealed a 924-bp open reading frame encoding a protein with a predicted
      molecular weight of 34,768. The amino acid sequence of EfaA shows 55 to 60%
      homology to a group of streptococcal proteins, FimA from Streptococcus
      parasanguis, SsaB from Streptococcus sanguis, ScaA from Streptococcus gordonii,
      and PsaA from Streptococcus pneumoniae. Members of this group have been shown to
      be adhesins, and we hypothesize that EfaA may function as an adhesin in
      endocarditis.

PMID- 7822046
TI  - Attenuated live cholera vaccine strain CVD 103-HgR elicits significantly higher
      serum vibriocidal antibody titers in persons of blood group O.
AB  - Persons of blood group O are at increased risk of developing cholera gravis. In a
      randomized, placebo-controlled, double-blind safety-immunogenicity trial of live
      oral cholera vaccine CVD 103-HgR in 5- to 9-year-old Chilean children,
      vibriocidal antibody seroconversion (74% overall) did not differ by blood group.
      However, the reciprocal geometric mean titer (GMT) in blood group O vaccines (GMT
      = 486) was higher than that in non-O vaccines (GMT = 179) (P < 0.02).

PMID- 7822047
TI  - Utilization of transferrin-bound iron by Haemophilus influenzae requires an
      intact tonB gene.
AB  - Haemophilus influenzae can utilize iron-loaded human transferrin as an iron
      source for growth in vitro. H. influenzae tonB mutants, containing a
      chloramphenicol acetyltransferase gene within their tonB genes, could bind iron
      charged human transferrin to their cell surfaces, but they were unable to utilize
      this serum glycoprotein as the sole source of iron for growth in vitro. In
      contrast, these tonB mutants were able to utilize an iron chelate (ferric
      ammonium citrate) for growth. Transformation of a tonB mutant with a plasmid
      encoding a wild-type H. influenzae tonB gene restored the ability of a tonB
      mutant to utilize iron-charged human transferrin. These results indicate that the
      uptake of iron from human transferrin by H. influenzae is a TonB-dependent
      process.

PMID- 7822048
TI  - Arthritogenicity of genetically manipulated Yersinia enterocolitica serotype O8
      for Lewis rats.
AB  - Yersinia enterocolitica strains of serotype O8 but not strains of other human
      pathogenic serotypes (e.g., O3 or O9) are able to induce a reactive arthritis
      like disease in Lewis rats after intravenous inoculation (J. L. Hill and D. T.
      Yu, Infect. Immun. 55:721-726, 1987). To assess which bacterial components or
      pathogenic factors are crucial for arthritis induction, six genetically
      manipulated Y. enterocolitica O8 derivatives have been compared with the parental
      strain in Lewis rats. Neither differences in the length of the lipopolysaccharide
      side chain (smooth to semirough) of Y. enterocolitica O8 nor replacement of the
      virulence plasmid (pYVO8) of Y. enterocolitica O8 with that of the
      nonarthritogenic Y. enterocolitica O9 (pYVO9) had a significant influence on
      arthritogenic potential or virulence in rats. Transposon insertional inactivation
      of the plasmid gene yadA encoding the Yersinia adhesin and the collagen-binding
      protein or of the secretion of YopH resulted in decreased arthritogenicity
      (increase of the arthritogenic infectious dose) and pathogenicity (decreased
      persistence of the pathogen in spleens and livers of rats and increase of the 50%
      lethal dose for mice). However, mutants impaired in yersiniabactin production or
      uptake proved to be nonarthritogenic for rats, probably because of pronounced
      attenuation in virulence. From these results, we conclude that the arthritogenic
      potential of Y. enterocolitica serotype O8 is closely related to the virulence
      potential determined as the 50% lethal dose in mice and the ability to persist in
      lymphatic tissue of Lewis rats. A specific arthritogenic determinant of Y.
      enterocolitica could not be identified.

PMID- 7822049
TI  - Differential induction of macrophage-derived cytokines by live and dead
      intracellular bacteria in vitro.
AB  - Marked differences in the abilities of living and heat-killed Brucella abortus
      and Listeria monocytogenes organisms to induce production of tumor necrosis
      factor alpha by in vitro-cultured macrophages were observed. Interleukin-1 and
      interleukin-6 appeared to be under different control. The results are discussed
      in relation to the induction of gamma interferon-producing Th1 cells and acquired
      cellular resistance to infection by living vaccines but not killed vaccines.

PMID- 7822051
TI  - Functional conservation among members of the Salmonella typhimurium InvA family
      of proteins.
AB  - InvA, which is essential for Salmonella spp. to enter cultured epithelial cells,
      is a member of a family of proteins involved in either flagellar biosynthesis or
      the secretion of virulence determinants by a number of plant and mammalian
      pathogens. The predicted overall secondary structures of these proteins show
      significant similarities and indicate a modular construction with a hydrophobic
      amino-terminal half, consisting of six to eight potential transmembrane domains,
      and a hydrophilic carboxy terminus which is predicted to reside in the cytoplasm.
      These proteins can be aligned over the entire length of their polypeptide
      sequences, with the highest degree of homology found in the amino terminus and
      clusters of conserved residues in the carboxy terminus. We examined the
      functional conservation among members of this protein family by assessing the
      ability of MxiA of Shigella flexneri and LcrD of Yersinia pseudotuberculosis to
      restore invasiveness to an invA mutant of Salmonella typhimurium. We found that
      MxiA was able to complement the entry defect of the invA mutant strain of S.
      typhimurium. In contrast, LcrD failed to complement the same strain. However, a
      plasmid carrying a gene encoding a chimeric protein consisting of the amino
      terminus of LcrD and the carboxy terminus of InvA complemented the defect of the
      Salmonella invA mutant. These results indicate that the secretory systems in
      which these proteins participate are functionally similar and that the Salmonella
      and Shigella systems are very closely related. These data also suggest that
      determinants of specificity may be located at the carboxy termini of these
      proteins.

PMID- 7822050
TI  - Sequencing of the gene encoding the major pilin of pilus colonization factor
      antigen III (CFA/III) of human enterotoxigenic Escherichia coli and evidence that
      CFA/III is related to type IV pili.
AB  - The plasmid-encoded structural gene cofA necessary for the production of the
      major pilin subunit of pilus colonization factor antigen III (CFA/III) of human
      enterotoxigenic Escherichia coli was identified, and the nucleotide sequence of
      the gene was determined. cofA consists of 714 nucleotides encoding a 238-amino
      acid protein (molecular weight of 25,309). CofA seems to be a precursor of
      CFA/III pilin, because the first 23 residues of the N-terminal amino acid
      sequence of the purified CFA/III pili coincided with the deduced amino acid
      sequence for residues 32 to 54 of CofA. Western blot (immunoblot) analysis of
      CofA also indicated its processing to form mature pilin in the presence of the
      downstream region of cofA. These results suggest that the major pilin of CFA/III
      pili is produced as a precursor form which is posttranslationally modified to the
      mature pilin and forms morphological pili after cleavage of the Gly-30-Met-31
      junction, probably by a protease encoded by an as-yet-unknown gene located
      downstream of cofA. Interestingly, the N-terminal 30-amino-acid sequence of
      mature CFA/III shows the highest identity (76.7%) to TcpA pilin of Vibrio
      cholerae, which is a type IV class B pilin.

PMID- 7822052
TI  - Identity of Streptococcus mutans surface protein antigen III and wall-associated
      protein antigen A.
AB  - Preparations of Streptococcus mutans surface proteins AgIII and antigen A from
      different laboratories were compared with regard to amino acid composition, N
      terminal amino acid sequence, electrophoretic mobility, and antigenic similarity.
      Despite previous observations of differences in physical properties, data
      indicate that these two preparations represent the same protein.

PMID- 7822053
TI  - Drug-resistant strains of Mycobacterium tuberculosis exhibit a range of virulence
      for mice.
AB  - A panel of clinical isolates of Mycobacterium tuberculosis, several of which were
      resistant to one or more antimycobacterial drugs, were tested for their capacity
      to give rise to active disease following aerogenic infection of normal
      immunocompetent mice. The panel exhibited a range of virulence in this model,
      which followed no clear trend in terms of geographical source, degree of drug
      resistance, or rate of growth in vitro. Several isolates grew very quickly over
      the first 20 days in mouse lungs before being contained by emerging immunity. In
      view of this latter observation, we hypothesize that it is possible that such so
      called fast growers may be responsible for the rapid fatality sometimes seen in
      immunocompromised patients with tuberculosis. Moreover, the results of the study
      do not support the belief that increased drug resistance usually associates with
      loss of virulence of the isolate.

PMID- 7822054
TI  - Dental amalgam--what are the alternatives?
AB  - Alternatives to amalgam include glass ionomer cements, direct placement
      composites, composite inlays, and ceramic inlays. Glass ionomer cements are
      suitable only in minimally stress-bearing areas but have the advantages of
      reliable adhesion and fluoride release. For the larger cavity, resin inlays offer
      a viable alternative to direct placement composites because of better control of
      contour and contact areas, and management of polymerisation shrinkage. However,
      there are reservations regarding the long-term marginal quality in view of
      possible wear of the cement lute. Ceramic inlays offer maximum aesthetics, but
      similar cement lute concerns have been expressed. The cost of the restoration to
      the patient is in the order direct resin < resin inlay < ceramic inlay. Tooth
      coloured resin or ceramic alternatives to amalgam are indicated for aesthetic
      restoration of moderate lesions, in patients with good oral hygiene.
      Contraindications include high caries rate, inability to obtain perfect moisture
      control, heavy occlusal stress, and poor or absent marginal enamel.

PMID- 7822055
TI  - Periodontal conditions and treatment needs (CPITN) in a worker population in
      Araraquara, SP, Brazil.
AB  - This research was carried out to assess the periodontal conditions and treatment
      needs in a worker population at Sugar and Alcohol Refineries in Araraquara, SP,
      Brazil. A sample of 528 workers aged 18-64 years was examined by one examiner,
      previously trained, using the CPITN. The results showed that calculus was the
      most frequently observed periodontal condition in the age groups 18-19, 20-24, 25
      29 and 30-34. In the age groups 35-44 and 45-64, the periodontal condition most
      frequently observed was shallow pockets. The analysis of the results showed that
      treating all conditions in all persons would demand an amount of care that could
      not be provided by any dental service. Therefore, the priority should be based on
      population strategy and primary prevention programmes to benefit the periodontal
      health of the majority of people.

PMID- 7822056
TI  - How to integrate prevention into a successful practice.
AB  - Research in the last three decades has shown the infectious nature of dental
      caries and periodontal diseases, and the feasibility of their prevention. This
      well established, albeit incomplete, knowledge has the potential to entirely
      change the way in which most dental practices are now operating. This change
      should ideally turn the traditional treatment-oriented practice into a different
      type in which the main emphasis is placed on preventive care. This goal can be
      achieved in most dental offices if the dentist follows some simple rules and
      guidelines which are currently accepted as effective measures to prevent oral
      diseases. Finally, personal data is presented suggesting that such preventive
      measures can be successfully implemented in a private practice.

PMID- 7822057
TI  - Cost: benefit of prevention in practice.
AB  - An enquiry among 50 successful, general dental practitioners working under a
      capitation payment system for the treatment of children, showed that they all
      thought that prevention on selected patients was of value to their practice. They
      said that prevention enhances the reputation of the practice, adds to the job
      satisfaction of the dentist and is part of modern dental philosophy. However,
      only when practised selectively would it be cost: beneficial. The most popular
      preventive treatments were fissure sealants, particularly when used on selected
      patients, oral hygiene demonstrations and, among a group of enthusiastic
      dentists, dietary counselling. Dentists who employed hygienists had a
      significantly higher 'mean preventive awareness score' than those who did not.

PMID- 7822058
TI  - Some aspects of trends and relationships in dental and medical education.
AB  - Dental education is dynamic. Many factors--economic, pedagogical, managerial,
      logistic, trends in disease patterns and delivery systems--are influencing its
      future directions and relationships with medical and other health professions'
      education. This article attempts to highlight those trends and relationships, at
      least in part of the world.

PMID- 7822059
TI  - Enamel opacities and dental caries in children who used a low fluoride toothpaste
      between 2 and 5 years of age.
AB  - A recent clinical trial investigated the cariostatic effectiveness of a low (550
      ppm) fluoride toothpaste in comparison with a standard (1050 ppm) control paste
      in pre-school children who were 2-years-old at the start of the 3-year trial. The
      present study has investigated the prevalence of enamel opacities in permanent
      incisor teeth and of caries in children who had taken part. As well as children
      from test and control groups, a third group of non-trial children were included
      in the sample. A total of 1,523 children were examined in schools and had
      photographs taken of their upper permanent incisor teeth. The latter were scored
      using the Thylstrup and Fejerskov (TF) index for fluorosis and the modified
      Developmental Defects of Enamel (DDE) index. Differences between the groups were
      small in real terms but using the TF index the child and tooth prevalence of
      opacities were significantly lower in the children who had used the test paste
      with a lower fluoride content; the same trend was seen in diffuse defects scored
      using the modified DDE index. There was no significant difference in the
      prevalence of caries in either primary or permanent teeth although the trend in
      both cases was for slightly more disease in children who had used the test paste.

PMID- 7822060
TI  - Survey of infection control procedures in New Zealand dental practices.
AB  - A national survey was conducted to investigate current procedures in New Zealand
      dental practices for control of cross-infection, and to gauge dentists'
      perceptions of their current procedures. A questionnaire was sent to all dental
      practices in New Zealand, and non-returns were followed up by two further
      mailings. From three mailings 767 useable questionnaires were returned (71.3 per
      cent of those sent out, 79.0 per cent of those potentially valid). Responses
      indicated that formal guidelines were generally well received, but varying
      proportions thought that some recommendations were unrealistic or irrelevant.
      Asked whether the dental practice offered treatment to 'high risk' (HIV-positive
      or HBAg-positive) patients, 25.3 per cent responded that none sought treatment.
      Almost all practices (92.0 per cent) had an autoclave, but only 42.8 per cent of
      practices autoclaved dental handpieces, and 10.9 per cent of practices wiped,
      cold disinfected or boiled extraction forceps. The large majority of responses
      complied with guidelines, but specific difficulties were identified with regard
      to sterilisation of handpieces.

PMID- 7822062
TI  - The transmission of knowledge from dentistry and dental science to the press
      during the period 1981-1990.

PMID- 7822061
TI  - Analysis of dental adhesive systems using scanning electron microscopy.
AB  - This study used scanning electron microscopy (SEM) to evaluate the effects of
      various acid conditioners (etchants) on dentine surfaces. The conditioners
      completely removed the smear layer from dentine and opened the dentinal tubules,
      but some also left debris or a reaction product on the surface. The study also
      evaluated the resin-dentine interfaces produced by five new-generation dentine
      bonding systems: All-Bond 2, Amalgambond, Gluma 2000, OptiBond, and Scotchbond
      Multi-Purpose. All-Bond 2, Amalgambond, OptiBond, and Scotchbond Multi-Purpose
      formed acid-resistant hybrid layers and intra-tubular resin tags when they were
      applied to visibly moist dentine.

PMID- 7822063
TI  - The relation between upper arm dimensions and maximal oxygen uptake during arm
      exercise.
AB  - The relationship between upper arm dimensions and maximal oxygen uptake (VO2peak)
      during arm exercise was investigated. Nineteen almost untrained male subjects (22
      +/- 2 yrs, 183 +/- 5.5 cm, 74 +/- 7.5 kg; mean +/- SD) volunteered to take part
      in the study. The following anthropometrical upper arm data were obtained for
      each subject: upper arm circumference, biceps and triceps skinfold thickness,
      upper arm length. From these data the cross-sectional area of the muscles, of the
      muscles plus bone of the upper arm, and the upper arm muscle volume were
      calculated. Upper arm volume was determined by water immersion. The subjects
      performed arm cranking with an increasing load of 10 watt each minute (Wpeak 125
      +/- 17.4 watt, VO2peak: 2.54 +/- 0.33 l/min; mean +/- SD). Multiple regression
      analyses showed that VO2peak could be best explained by the cross-sectional area
      of the muscles plus bone of the upper arm (r = 0.65, p < 0.005). Other factors
      did not add significantly. The variables as body mass, fatfree body mass, upper
      arm volume and total arm volume correlated less well with VO2peak (r < 0.5). In
      conclusion it is suggested to use the easily obtainable cross-sectional area of
      the muscles plus bone of the upper arm to standardize VO2peak of arm cranking.

PMID- 7822064
TI  - Effects of exercise training modality on glucose tolerance in men with abnormal
      glucose regulation.
AB  - To determine the effects of exercise training modality on glucose tolerance in
      men with untreated abnormal glucose regulation, 26 untrained men (age 54 +/- 9
      years; mean +/- SD) with either non-insulin-dependent diabetes mellitus (N = 8),
      impaired glucose tolerance (IGT) (N = 12) or hyperinsulinemia with normal glucose
      tolerance (N = 6) were studied before and after 20 wk of either strength training
      (ST) (N = 8), aerobic (treadmill walk/jog) training (AT) (N = 8), or no exercise
      (control group; N = 10). Plasma concentrations of glucose and insulin were
      measured after a 12-14 hr fast and during a standard oral glucose tolerance test
      (OGTT) before and after training. The ST program significantly reduced total
      plasma glucose area (mmol.l-1.120 min-1) under the OGTT curve (1348 +/- 251 vs
      1190 +/- 329, p < 0.05), and plasma glucose levels (mmol.l-1) at 60 min (p <
      0.05), 90 min (P < 0.05), and 120 min (p < 0.05) after glucose ingestion.
      Strength training also lowered the total plasma insulin area (pmol.l-1.120 min-1)
      under the OGTT curve (60082 +/- 25467 vs 46727 +/- 11273, p < 0.05) as well as
      plasma insulin levels (pmol.l-1) at fasting (p < 0.05) and at 90 min (p < 0.01)
      and 120 min (p < 0.05) after glucose ingestion. All men with IGT (four in each
      training group) normalized their glucose tolerance following the training. There
      were no significant differences in OGTT results between ST and AT and no changes
      were observed in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7822065
TI  - Stretch reflex responses following mechanical stimulation in power- and endurance
      trained athletes.
AB  - The basic stretch reflex responses evoked by the mechanical stimuli were
      investigated among different athletic groups. The tests were performed by a
      special ankle ergometer, which created dorsiflexion velocities from 25 deg x s-1
      to 115 deg x s-1 around the ankle joint. The EMG activity of soleus (SO),
      gastrocnemius (GA) and tibialis anterior (TA) muscles was recorded with surface
      electrodes. In all subjects higher angular velocities caused higher stretch
      reflex responses. The endurance-trained athletes were more sensitive to the used
      stimuli than the power-trained athletes, because of their shorter latency times
      (43 +/- 7 ms vs 45 +/- 7 ms, p < 0.001 for the SO muscle and 40 +/- 8 ms vs 43 +/
      6 ms, p < 0.001 for the GA muscle), longer duration of action potentials and
      shorter recovery times of the monosynaptic reflex. Thus, the neural control of
      reflex movements in skeletal muscles was dependent on the training background of
      the subjects. Additionally, the findings may be explained by differences in the
      motor unit composition as well as by possible differences in the muscle spindle
      density of the two subject groups.

PMID- 7822066
TI  - Spironolactone administration and training-induced hypervolemia.
AB  - The purpose of this study was to determine the contribution of aldosterone to
      plasma volume expansion accompanying short-term exercise training. Twelve healthy
      males (age = 26.5 +/- 5.8) cycled for 120 min on three consecutive days at a
      relative exercise intensity of 65% VO2max. Half of the subjects were treated with
      25 mg of spironolactone taken four times daily to suppress the effects of
      aldosterone. Resting plasma volume increased significantly (501 +/- 83 ml, p <
      0.05) from pretraining in control subjects, but not for drug-treated subjects
      (163 +/- 94 ml). Spironolactone attenuated gains in resting plasma volume, serum
      sodium content, and serum osmolal content by 67%, 79% and 66%, respectively.
      Spironolactone-treated and non-treated subjects experienced similar increases in
      total serum protein content sufficient to increase the plasma volume by
      approximately 290 ml. It was not determined why drug-treated subjects attained
      less of a plasma volume expansion than that expected by the increase in oncotic
      pressure. In conclusion, two-fifths of the plasma volume expansion induced by 3 d
      of endurance cycling could be attributed to aldosterone activity, and the
      remaining three-fifths could be explained by the expansion of intravascular
      protein mass. Other neurohormonal influences may have contributed to the overall
      plasma volume expansion but this experiment did not allow for their exclusion.

PMID- 7822067
TI  - Coincidence of lactate threshold and HR-power output threshold under varied
      nutritional states.
AB  - The purpose of this study was to cross-validate the method of Conconi et al. (5)
      that purports to determine "anaerobic threshold" based on a deflection point
      between heart rate (HR) vs power output. Eight males (22.6 +/- 1.6 y) were tested
      with maximal progressive cycle ergometry under normal (NG) and glycogen-depleted
      (GD) conditions. During the last min of each stage, HR was monitored via EKG and
      blood was sampled for lactate determination. Computerized data analysis was then
      conducted to determine the deflection points for lines respectively fit to each
      HR vs power output (heart rate threshold; HRT) and lactate vs power output
      (lactate threshold; LT) distribution. Under NG conditions, HRT and LT occurred at
      200.4 +/- 33.3 and 211.4 +/- 46.5 watts, respectively (equivalent to VO2 = 2.455
      +/- 0.368 and 2.618 +/- 0.507 l/min), with a correlation of r = 0.68 between HRT
      vs LT (S.E.E. for prediction of LT from HRT = 36.7 watts). However, under GD
      conditions, HRT = 182.9 +/- 43.3 watts and LT = 227.0 +/- 41.1 watts (equivalent
      to VO2 = 2.395 +/- 0.413 and 2.944 +/- 0.578 l/min) with HRT vs LT r = -0.04 and
      S.E.E. = 44.4 watts. Across the two conditions, < 4% of the variance in the
      change in LT was accounted for by the change in HRT. These data indicated that 1)
      under NG conditions the modest association between HRT and LT was not causally
      linked and 2) HRT was not a stable predictor of LT across varying nutritional
      states such as those common to prolonged exercise.

PMID- 7822068
TI  - Body-mass-modified running economy and step length in elite male middle- and long
      distance runners.
AB  - To minimize the influence of body mass on oxygen uptake (VO2) during running,
      submaximal and maximal VO2 should preferentially be expressed as ml.kg-0.75.min
      1. In this study, the levels of such body-mass-modified running economy were
      investigated at different velocities in elite runners and related to step lengths
      and anthropometric measures. Twenty-six Swedish National Team middle- and long
      distance runners performed submaximal (4 velocities) and maximal treadmill tests.
      In 17 runners repeated (2-4) tests were performed within 6 months. The maximal
      oxygen uptake (VO2max; 214 vs 202 ml.kg-0.75.min-1) and running velocity at 4
      mmol.l-1 blood lactate were higher in the long- (n = 12) than in the middle
      distance group (n = 14). The oxygen uptake at 15 km.h-1 (VO2 15) was lower (129
      vs 138 ml.kg-0.75.min-1, p < 0.01) and the VO2/velocity slope higher in the long
      distance runners, with similar VO2 18 in the two groups. Step lengths at 18 (168
      vs 173 cm) and 15 km.h-1 did not differ significantly between the groups, but the
      increase in step length per km.h-1 velocity raise was greater in the middle
      distance runners. Step lengths at these velocities were positively related to
      body mass and stature, negatively to relative leg length. Stature and leg length
      were greater in runners displaying low VO2 15, whereas no corresponding
      difference was seen for VO2 18. The figures for running economy at 15 and 18 km.h
      1 were poorly related to the concomitantly determined step lengths at the
      respective velocities.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7822069
TI  - Differential expression of interleukin-2 receptor alpha and beta chains in
      relation to natural killer cell subsets and aerobic fitness.
AB  - Immunophenotyping by dual parameter flow cytometry was used to compare the
      expression of interleukin-2 receptor alpha and beta chains on lymphocyte subsets
      in the peripheral blood of 7 trained and 6 untrained volunteers (respective
      VO2max 57.0 +/- 6.1 and 39.0 +/- 4.5 ml.kg-1.min-1). Venous blood samples were
      collected at least 36 h after the most recent exercise session. The trained
      subjects had higher circulating counts (10(9).l-1) of total leukocytes (5.80 +/-
      0.83 vs. 4.63 +/- 0.21, p < 0.05), granulocytes (3.14 +/- 0.72 vs. 1.90 +/- 0.30,
      p < 0.05), and NK cells (CD16+, 0.32 +/- 0.14 vs. 0.16 +/- 0.05, p < 0.05; CD56+,
      0.41 +/- 0.14 vs. 0.21 +/- 0.03, p < 0.01), but lower lymphocyte counts than
      their sedentary peers (1.90 +/- 0.22 vs. 2.26 +/- 0.25, p < 0.05). Counts for T
      cells (CD3+) and B cells (CD19+), and the CD4+/CD8+ ratio did not differ between
      the two subject groups. The p55-IL-2 receptor alpha expression (CD25+: 0.63 +/-
      0.11 vs. 0.69 +/- 0.17) was unrelated to training, but the p70-75-IL-2 receptor
      beta expression was higher in the active group (p70/Mik-beta 1+: 0.42 +/- 0.09
      vs. 0.20 +/- 0.06, p < 0.001; p75/TU27+: 0.36 +/- 0.08 vs. 0.17 +/- 0.07, p <
      0.005). Beta chain co-expression was also higher on NK cell subsets (p < 0.001)
      in trained than in sedentary subjects. Aerobic power was strongly correlated with
      IL-2R beta expression (r = 0.914, p < 0.001 for Mik-beta 1; r = 0.884, p < 0.005
      for TU27).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7822070
TI  - Immunological status of competitive cyclists before and after the training
      season.
AB  - The total number of leucocytes, T lymphocyte subsets, mitogen induced
      proliferation of lymphocytes, Il-2 generation, adherence capacity and
      chemiluminescence of granulocytes were measured and a leukergy test performed in
      fifteen young cyclists. The investigations were carried out at rest at the
      beginning of a training season and after six months of intensive training and a
      racing season, cycling approximately 500 km a week. Baseline values of the tested
      immune parameters were within the range observed in 16 non-trained healthy
      controls except significantly increased non stimulated neutrophil
      chemiluminescence. The second cyclo-ergometer test in August showed a marked
      improvement in the performance capacity of the cyclists. Significant decrease in
      absolute numbers of CD3+ and CD4+ cells, diminished IL-2 generation and fMLP and
      PMA stimulated chemiluminescence of neutrophils were noted. Surprisingly, a
      marked increase in lymphocyte proliferation induced by PHA and anti-CD3 MoAb and
      normalisation in non stimulated neutrophil chemiluminescence were also observed
      at rest after the training season. We conclude that long-lasting intensive
      training may result in significant alterations in lymphocyte number and
      composition and in neutrophil oxidative burst capacity, but their actual
      significance for immunity is seen controversially.

PMID- 7822071
TI  - Morphological and clinical aspects of heterotopic ossification in sports. A case
      study.
AB  - Heterotopic ossification (HO) caused through sport injuries is a rare, clearly
      defined lesion. In a considerable number of cases, however, no adequate trauma
      can be remembered or otherwise established in the "sporting history".
      Differential diagnosis of this non-traumatic HO variant often presents many
      problems which may lead to the wrong diagnosis of sarcoma. We looked at 28 cases,
      in which in more than 50% a sarcoma was discussed as primary diagnosis. These
      difficulties arise mainly in cases where clinical features suggest a tumor,
      radiological changes are unspecific, and the diagnosis is based on a small biopsy
      sample. We demonstrate and discuss the problems involved in differential
      diagnosis using the history of a matchgrade sportsman as a sample. Unlike in
      sarcoma, patients with HO usually suffer severe pain, and well over 50% of all
      patients develop the disease during the 2nd or 3rd decade. Over 90% of all
      patients with soft tissue sarcoma, however, are over the age of 30. From the
      morphological point of view, the different histological pattern of HO has to be
      taken into account, since early stages may mimick a sarcomatous lesion. If the
      clinical findings suggest the presence of HO, surgical intervention including the
      taking of biopsy sample should be postponed, so that instead of early highly
      mitotic active phases more mature bone structures, which are easier to classify,
      will be available for evaluation. Only a profound knowledge of the different
      phases of HO, together with clinical and radiological features, will clarify the
      differential diagnostic problems of the non-traumatic variant of this lesion in
      sportsmen.

PMID- 7822072
TI  - The influence of ankle sprain injury on muscle activation during hip extension.
AB  - The likely influence of a localised injury in a distal joint on the function of
      proximal muscles is an important consideration in assessment and treatment of
      musculoskeletal injuries. However, little experimental evidence in humans exists
      in this area. Accordingly, a controlled study was carried out, in which the
      function of muscles at the hip was compared between subjects who had suffered
      previous severe unilateral ankle sprain and matched control subjects. The pattern
      of activation of the gluteus maximus, the hamstring muscles and the ipsilateral
      and contralateral erector spinae muscles was monitored through the use of surface
      electromyography during hip extension from prone lying. Analyses revealed that
      the pattern of muscle activation in subjects with previous injury differed
      markedly from normal control subjects, and that changes appeared to occur on both
      the uninjured and the injured sides of the body. A significant difference between
      the two groups was the delay in onset of activation of the gluteus maximus in
      previously injured subjects. The existence of remote changes in muscle function
      following injury found in this study emphasise the importance of extending
      assessment beyond the side and site of injury.

PMID- 7822073
TI  - Altitude training did not speed up the progression of running performance in man.

PMID- 7822074
TI  - Validity of the Cosmed K2 instrument as a telemetric VO2 detector in playing
      athletes directly on the game court.

PMID- 7822075
TI  - Serotonin1C,2 receptors and endurance performance. An illustration of the limits
      of pharmacological tools in exercise science.

PMID- 7822076
TI  - Kaposi's sarcoma.

PMID- 7822077
TI  - Cutaneous scars: Part II.

PMID- 7822078
TI  - Do environmental factors play any role in the pathogenesis of mycosis fungoides
      and Sezary syndrome?

PMID- 7822079
TI  - Women in dermatology: a personal view. IX.

PMID- 7822080
TI  - Xeroderma pigmentosum variant: DNA ploidy analysis of various skin tumors and
      normal-appearing skin in a patient.
AB  - BACKGROUND: The patient with xeroderma pigmentosum provides an appropriate human
      model for the evaluation of tumor development and progression. METHODS: We
      describe a patient with variant-type xeroderma pigmentosum who developed actinic
      keratoses, a squamous cell carcinoma, and its metastasis into a lymph node. DNA
      ploidy was measured and analyzed in cells of these tumors and the patient's sun
      exposed as well as sun-shielded skin. RESULTS: The sun-shielded skin showed a
      normal diploid DNA distribution pattern, while the sun-exposed skin had an
      increased number of hyperdiploid cells. The actinic keratosis showed further
      increased hyperdiploid cells. The squamous cell carcinoma showed a large number
      of hyperdiploid cells and formed an aneuploid cell fraction. Histographically,
      the aneuploid cell fraction became more apparent and was revealed to be a major
      fraction in the metastatic squamous cell carcinoma. CONCLUSIONS: The changes in
      the DNA ploidy pattern well reflect the clinical and histologic characteristics
      of the respective skin conditions and likely provide the cellular basis for the
      sequential or stepwise carcinogenic process in the patient's xeroderma
      pigmentosum skin. Further studies are necessary to determine whether the present
      results explain the similar carcinogenic process in sun-damaged skin of the
      nonpredisposed general population.

PMID- 7822081
TI  - Statistical definition of nailfold capillary pattern in patients with psoriasis.
AB  - BACKGROUND: The microvasculature plays an important role in the pathogenesis of
      psoriatic skin lesions. Our purpose was to try to define a psoriatic pattern in
      the nailfold capillary, to clarify the relationship between nailfold capillary
      microscopic changes and nail involvement and to note the general clinical
      features of psoriasis. METHODS: Image analysis of nailfold capillaries was
      performed in 62 patients with psoriasis. The capillary pattern was defined
      statistically comparing it with that of 51 healthy volunteers. We attempted to
      differentiate the psoriatic pattern from normal controls with "canonical
      discriminant analysis." RESULTS: Forty-nine of 62 patients with psoriasis could
      be differentiated from normal controls by our definition of psoriatic pattern
      that was significantly correlated with periungual psoriatic plaque, nail pitting,
      onycholysis, and the extent of the involved area. CONCLUSIONS: Our data suggest
      that nailfold capillary changes reflect microvascular changes of psoriasis and
      that the nailfold capillary pattern is a useful tool in evaluating nail
      involvement and the severity of psoriasis.

PMID- 7822082
TI  - Elevated serum nickel concentration in psoriasis vulgaris.
AB  - BACKGROUND: Psoriasis vulgaris is a common skin disease afflicting 1-3% of the
      American population. Its pathogenesis remains unknown despite concerted research
      efforts. Our purpose was to study baseline serum nickel concentrations in
      psoriasis vulgaris subjects and in healthy control subjects. METHODS: Sixteen
      psoriasis vulgaris subjects with active disease (in 14 of moderate to marked
      severity), and 11 age- and sex-matched healthy control subjects were studied.
      Serum nickel determinations were performed using electrothermal atomic absorption
      spectrophotometry (ETAAS). RESULTS: Despite the relatively small sample size,
      significant elevation of mean serum nickel concentration was found in the
      psoriasis group compared to the control group (P = 0.019). CONCLUSIONS:
      Recognition of abnormal nickel homeostasis could point the way to greater
      understanding of the primary biochemical defect in the psoriatic process.
      Alternatively, this finding may mark an association without pathogenic
      significance. Further investigation is needed.

PMID- 7822083
TI  - Ultrasound imaging of psoriatic skin: a noninvasive technique to evaluate
      treatment of psoriasis.
AB  - BACKGROUND: The aim of our study was to image psoriasis plaques by ultrasound to
      assess the changes in psoriasis and to measure and quantify them objectively.
      MATERIALS AND METHODS: Thirty-one psoriasis plaques were studied in 19 patients.
      Measurements of skin thickness were obtained with a high resolution B-mode
      echographic system. RESULTS: Some changes were seen in psoriatic skin. A new
      structural element was observed: a wide subepidermal nonechogenic band. The other
      changes were a decrease in dermal echoes that were less intense and less dense,
      and an increase in the epidermal and dermal skin thicknesses. The skin thickness
      was increased in all psoriasis plaques as compared to apparently normal skin (P <
      0.001). The average increase was 67% for whole skin and 200% for epidermis.
      CONCLUSIONS: Ultrasound imaging of psoriatic skin allowed the identification of
      different skin changes induced by psoriasis, and particularly, the
      differentiation between epidermal and dermal alterations. We presume that
      epidermal thickness reflects epidermal proliferation and desquamation, and the
      increase in the dermal and whole skin thickness reflects infiltration. We feel
      that ultrasound imaging of psoriatic skin is a quantitative method that is as
      easy and noninvasive as the psoriasis area and severity index (PASI). It could be
      used for following up patients with psoriasis and could achieve widespread use,
      especially in research protocols.

PMID- 7822084
TI  - Fibroepithelial papilloma of the umbilicus.

PMID- 7822085
TI  - Colloid milium associated with multiple myeloma.

PMID- 7822086
TI  - Verruca vulgaris inoculated during tattoo placement.

PMID- 7822087
TI  - Rheumatoid neutrophilic dermatitis.

PMID- 7822088
TI  - Microcystic adnexal carcinoma: successful management using Mohs' micrographically
      controlled surgery.

PMID- 7822089
TI  - Treatment of oral pemphigus vulgaris.
AB  - BACKGROUND: Oral pemphigus is considered to represent either an initial stage of
      pemphigus vulgaris that should be treated with high doses of immunosuppressive
      drugs to prevent its spread to the skin or a variety of the disease that does not
      need aggressive treatment. The absence of a widely accepted therapeutic method
      and the obscure nature of this disease prompted this study. METHODS: Twenty-eight
      patients with oral pemphigus were randomly divided into three groups. The first
      group received only steroids at a dose of 40 mg of prednisone equivalent. In the
      other two groups the same dose of steroids was administered, but combined with
      either 100 mg of cyclophosphamide or 5 mg/kg of cyclosporine as an adjuvant.
      Direct immunofluorescence studies were performed on specimens obtained from both
      buccal mucosa and oral skin. RESULTS: There was no significant difference in the
      duration of treatment required to achieve remission and in the relapse rate among
      the three groups. The incidence of complications was higher with combination
      treatment. Deposited immunoreactants were detected with equal frequency in
      specimens obtained from the buccal mucosa and normal skin. CONCLUSIONS: Oral
      pemphigus most likely represents an initial stage of a disease that can become
      generalized. Administration of moderate doses of steroids alone is effective in
      controlling the disease.

PMID- 7822090
TI  - Efficacy of short-contact therapy with dithranol in childhood psoriasis.
AB  - BACKGROUND: Dithranol is a potent reducing substance and is thought to achieve
      its effect on psoriasis by reduction of cell turnover. It was shown to be
      efficacious in adults, but its efficacy has not been documented in children.
      METHODS: The efficacy of short-contact therapy, a dithranol cream preparation,
      was retrospectively evaluated in 58 children with psoriasis. Dithranol cream (0.1
      2%) was applied daily for 30 minutes to affected skin areas. Patients were
      evaluated at 1-4-week intervals. RESULTS: The median duration of therapy before
      the onset of remission was 2 months. Remission was achieved in 81% of the
      children. The median duration of remission was 4 months. Mild adverse skin
      reactions occurred in 20% of patients, but only one patient had to discontinue
      therapy. CONCLUSION: Short-contact therapy with dithranol cream preparation is an
      effective and well-tolerated treatment for childhood psoriasis. A thorough
      explanation of the disease and mode of therapy to patients and their parents is
      essential for good compliance and subsequent success.

PMID- 7822091
TI  - Induction of psoriasiform changes in guinea pig skin by propranolol.
AB  - BACKGROUND: The ability of beta-adrenergic blocking agents to induce psoriasis as
      an adverse effect prompted us to use such an agent to induce psoriasis in guinea
      pigs. METHODS: Thirty female albino guinea pigs were divided into four groups.
      Group 1 received propranolol, 0.1 mg/day, dissolved in 2 mL of normal saline,
      orally by gavage for 30 days. Group 2 was given the same treatment, but in
      addition intradermal injections of propranolol with Freund's complete adjuvant,
      injected at weekly intervals. Group 3 (five animals) received 2 mL saline, and
      group 4 additional injections of adjuvant without propranolol. Groups 3 and 4
      served as normal controls. RESULTS: All animals of group 2 (which received
      propranolol orally and in addition intradermal injections of adjuvant) developed
      psoriasiform epidermal hyperplasia with acanthosis. Parakeratosis,
      papillomatosis, and formation of microabscesses, all characteristic signs of
      psoriasis, have not been seen in any of the skin samples of this group. Skin
      samples from group 1 animals receiving propranolol orally showed normal epidermis
      and dermis. They showed exactly the same histologic picture as the control groups
      3 and 4. CONCLUSIONS: Beta-blockers given orally for 30 days do not cause any
      significant skin changes in guinea pigs. When given with a weekly intradermal
      injection of Freund's complete adjuvant, they cause psoriasiform epidermal
      hyperplasia. Although the overall histologic appearance of the skin of group 2
      resembled psoriasis, it lacked important histologic features characteristic of
      this disease. It seems, therefore, that the model, per se, does not fulfill the
      initial expectations as an experimental model for psoriasis; however, this model
      has potential in the study of adverse drug reactions. Perhaps by introducing
      modifications to the experimental protocol, we may succeed also in developing a
      better model for experimental psoriasis.

PMID- 7822092
TI  - Treatment of plane warts by tretinoin-induced irritant reaction.

PMID- 7822093
TI  - Geography of dermatology publication.

PMID- 7822094
TI  - Successful therapy of a complicating periorbital angiomatous nevus with oral
      prednisolone.

PMID- 7822095
TI  - Protected peptide disulfides by oxidative detachment from a support.
AB  - A new and efficient procedure for the preparation of protected cyclized and
      protected symmetrical dimeric peptide disulfides is described. A thiol is
      immobilized onto a solid phase through coupling of the thiol function with a
      resin-linked trityl group. Following conventional peptide assembly using the Fmoc
      strategy, detachment is performed by oxidation with iodine in a suitable organic
      solvent. When N,N-dimethylformamide is used as the solvent, and the peptide chain
      contains an acetamidomethylthio function, located N-terminally in a N alpha-(9
      fluorenylmethyloxycarbonyl), or N alpha-tert-butyloxycarbonyl cysteinyl residue,
      or occurring in the chain, then the corresponding fully protected cyclic peptide
      disulfide will be obtained in high yield and purity. In other solvents (e.g.
      dioxane or chloroform-methanol 1:1, v/v), the iodine-mediated oxidation gave not
      only the cyclic product, but also substantial amounts of the parallel symmetrical
      dimeric peptide retaining Cys(Acm) at the two identical N-termini.

PMID- 7822096
TI  - Structural characteristics of diproline: a new crystal form of tBoc-Pro-Pro-OH.
AB  - The structure of a new crystalline form of tBoc-Pro-Pro-OH (C15 H24 N2 O5) has
      been determined. The crystals were monoclinic, P2(1), a = 14.667(5), b =
      16.600(4), c = 15.502(3) A, beta = 117.84(2) degrees, V = 3337.2 A3 and Z = 8, Dc
      = 1.24 g/cm3. There are four molecules in the asymmetric unit, each displaying
      polyproline-type structure but differing in the proline pucker. All four
      molecules display a twist conformation in the first proline ring, with molecules
      A, B and C being beta gamma T (P approximately 183 degrees, tau approximately 33
      for A and B, tau approximately 18 for C) and molecule D between gamma beta T and
      gamma E (P = 10 degrees, tau approximately 38). The second residue of all four
      molecules has an envelope conformation. Molecules A and B display an alpha E
      conformation (P approximately 126 degrees, tau approximately 25) and molecules C
      and D display a beta E conformation (P approximately 168 degrees, tau
      approximately 37). The molecules are hydrogen-bonded (O...OH), forming helical
      channels along the alpha-axis.

PMID- 7822097
TI  - Diketopiperazine formation and N-terminal degradation in recombinant human growth
      hormone.
AB  - A new degradation process has been identified that occurs in recombinant DNA
      derived human growth hormone. Non-enzymatic cyclization of the first two amino
      acids from the N-terminus and subsequent cleavage results in the formation of a
      diketopiperazine and a truncated variant of rhGH. The truncated protein was
      separated using hydrophobic interaction chromatography and identified as
      desPhe1Pro2-rhGH using N-terminal sequence analysis, tryptic mapping, and mass
      spectrometry.

PMID- 7822098
TI  - Conformations of cyclic pentapeptide endothelin receptor antagonists.
AB  - The solution conformations in methanol and chloroform of the endothelin A
      receptor antagonists cyclo(dV-L-dW-dD-P), 1, and cyclo(dV-N alpha-MeL-dW-dD-P),
      2, have been studied by NMR spectroscopy at room temperature and below. In these
      solvents, both peptides were found to have a well defined peptide backbone
      conformation composed of a type II beta turn at the Leu-D-Trp and a gamma' turn
      at Pro. This conformation is in agreement with results reported for 1 in other
      solvents and consistent with the expected location of the N-methyl substituent in
      that backbone. In methanol, both peptides show NOE and chemical shift evidence of
      close contact between the Leu and D-Trp side chains. This interaction is greatly
      reduced or absent in chloroform, and is stronger in methanol at 203 K than at 298
      K.

PMID- 7822099
TI  - Structure-activity and conformational studies of a series of modified C-terminal
      hexapeptide neurotensin analogues.
AB  - Neurotensin (NT), is a linear tetradecapeptide (pGlu1-Leu2-Tyr3-Glu4-Asn5- Lys6
      Pro7-Arg8-Arg9-Pro10-Tyr11-Ile12-Leu13) that has been found in the central
      nervous system and peripheral tissues and appears to have a variety of
      physiological properties. A C-terminal hexapeptide analogue [N alpha Me-Arg-Lys
      Pro-Trp-Tle-Leu, (1) Tle = tert-leucine] has recently been reported to have high
      affinity for the NT receptor and appears to possess central activity after
      systemic administration. In an effort to probe the structure-activity and
      conformational properties of the dipeptide, Pro-Trp for binding and functional
      activity, these residues have been substituted with several natural and unnatural
      amino acids. Some of these analogues have binding affinities similar to compound
      1, while in other cases, such as D-amino acid substitutions, the peptides had
      negligible binding affinity. In general, the Pro10 position seems more tolerant
      of substitution by amino acids that favor a reverse turn, rather than those that
      favor an extended conformation. The Trp11 position accepted extra steric bulk
      more readily than conformational constraints.

PMID- 7822100
TI  - Secondary structure prediction from multiple sequence data: blood clotting factor
      XIII and Yersinia protein-tyrosine phosphatase.
AB  - Predictions of protein structure are best tested without prior knowledge of the
      protein three-dimensional structure. Three-dimensional atomic models will soon be
      determined by X-ray crystallography for the alpha-subunit of human blood clotting
      factor XIII and members of the family of protein tyrosine specific phosphatases.
      Accordingly, we here present secondary structure predictions for each of these
      proteins. The secondary structure predictions were generated from aligned sets of
      protein sequences. This technique has previously provided reliable predictions
      for the Annexins and the SH2 domains. The factor XIII alpha prediction contains
      39 regions predicted in strand conformation (34% of the protein) with only 3
      helices (4%). The protein tyrosine phosphatases have 12 predicted strands and 5
      helices (30 and 17%, respectively). We expect greater reliability from regions of
      alignments that show clear patterns of residue conservation (61% of factor XIII
      alpha and 57% of the protein tyrosine phosphatases). The aligned protein tyrosine
      phosphatases show two regions (L39-L80 and I138-E253) with clear patterns of
      residue conservation separated by a region of variable amino acid composition. We
      suggest this indicates that the tyrosine phosphatase fold comprises two domains
      separated by an exposed linker. Potential phosphate binding sites are identified
      in the protein tyrosine phosphatases.

PMID- 7822101
TI  - alpha-Amylases from Thermoactinomyces vulgaris: characteristics, primary
      structure and structure prediction.
AB  - Two amylolytic active protein fractions (named alpha-amylase 1 and alpha-amylase
      2) were isolated from the bacterium Thermoactinomyces vulgaris strain 94-2A.
      alpha-Amylase 1 had a molecular mass of 51.6 kDa, whereas alpha-amylase 2
      consists of two fragments which have molecular masses of 17.0 and 34.6 kDa,
      respectively. These two fragments are products from a proteolytic cleavage of
      alpha-amylase 1 at amino acid position 303 (tryptophan) by a serine protease
      (thermitase) which is also produced by T. vulgaris. The purified alpha-amylase 1
      and 2 follow the Michaelis-Menten kinetics in the presence of starch as substrate
      with Km values of 1.37 +/- 0.07 and 1.29 +/- 0.18 mg/mL, respectively. In effect
      they differ in their stability characteristics. The amino acid sequence of alpha
      amylase from T. vulgaris derived from DNA sequence (1) was compared with those of
      other alpha-amylases. It reveals high homologies to alpha-amylases from other
      microorganisms (e.g. B. polymyxa, A. oryzae, S. occidentalis and S. fibuligera).
      A three-dimensional structure model for alpha-amylase 1 on the basis of the 3 A X
      ray structure of Taka-amylase was constructed.

PMID- 7822102
TI  - Design and synthesis of novel inhibitors of prohormone convertases.
AB  - Prohormone convertase-1 (PC1) and furin are subtilisin-like endopeptidases
      involved in the biosynthesis of peptide hormones. Five decapeptides representing
      the junction between the pro-region and the catalytic region of PC1 were
      prepared. The core sequence corresponded to D-Tyr-Arg-Ser-Lys-Arg- Xaa-Val-Gln
      Lys-Asp where D-Tyr replaces the native Glu residue and Xaa, representing the P1'
      position, corresponds to L-Ser, L-Leu or the unnatural amino acids, D-Ser, beta
      Ala, gamma-Abu, beta-Cha or gamma-Hyp. Another analog incorporating an Orn
      residue in place of the Arg at the P1 site was also prepared. These peptides,
      synthesized by solid-phase Fmoc chemistry, were fully characterized by FAB-MS, 1H
      NMR and amino acid composition. Except for Orn, gamma-Hyp, L/D-Ser and L-Leu
      containing analogs, the others were found to be moderate to potent competitive
      inhibitors of hPC1 activity in the following order: gamma-Abu > beta-Cha > beta
      Ala, with Ki values ranging from 1 to 8.6 microM. Both L-Ser and L-Leu analogs
      were correctly cleaved at the acyl carbon COOH-terminal to the Lys-Arg pair by
      human PC1, whereas beta-Cha, gamma-Abu, beta-Ala and D-Ser analogs proved to be
      very poor substrates. The Orn and gamma-Hyp derivatives were not cleaved by the
      enzyme at all. The three analogs containing beta-Cha, gamma-Abu and beta-Ala also
      proved to be potent inhibitors of the human furin activity in the following
      order: beta-Ala > beta-Cha > gamma-Abu, with Ki ranging from 0.8 to 2.2
      microM.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7822103
TI  - Inductive effects on the structure of proline residues.
AB  - 4(S)-Hydroxyproline (Hyp) residues constitute about 10% of most forms of
      collagen, the most abundant protein in vertebrates. X-Ray diffraction analysis
      was used to ascertain how the structure of proline residues is affected by the
      inductive effect elicited by the hydroxyl group of Hyp residues. N-Acetylproline
      methylester (1), N-acetyl-4(S)-hydroxyproline methylester (2) and N-acetyl-4(S)-
      fluoroproline methylester (3) were synthesized, and their crystalline structures
      were determined at high resolution. The amide bond of crystalline 1 was in the
      cis conformation, which is the minor isomer in solution, and the pyrrolidine ring
      of 1 had C gamma-endo pucker. In crystalline 2 and 3 the amide bonds were in the
      trans conformation, and the pyrrolidine rings had C-exo pucker. The lengths of
      the bonds between sp3-hybridized carbon atoms in the pyrrolidine ring were
      significantly shorter in 2 and 3 than in 1, as was predicted by ab initio
      molecular orbital calculations at the RHF/3-21G level of theory. No significant
      change in bond length was observed in the other bonds of 1,2 or 3. The
      pyramidylization of the nitrogen atom increased dramatically in the order: 1 < 2
      < 3. Together, these results indicate that electron-withdrawing substituents in
      the 4-position of proline residues can have a significant influence on the
      structure of these residues. In particular, the change in pyramidylization
      suggests that such substituents increase the sp3-character of the prolyl nitrogen
      atom and could thereby alter the rate of prolyl peptide bond isomerization.

PMID- 7822104
TI  - Amino acid sequence and properties of vasopressin-associated elephant
      neurophysin.
AB  - The primary structure of an elephant neurophysin, homologous to vasopressin
      associated neurophysins, is reported. The protein contains a Tyr for Asn
      substitution at position 75, a position in direct contact with residues 77 and 78
      of the monomer-monomer interface. This Tyr residue therefore serves as a
      potential reporter of the path involved in the long-range linkage between peptide
      binding and dimerization in this system. NMR studies of the protein in unliganded
      and liganded states demonstrated normal dimerization properties and the expected
      increase in dimerization associated with binding peptide. In keeping with an
      elevated pKa of 11.1 assigned to Tyr-75 by UV spectrophotometric titration, the
      NMR signals from the 3,5 and 2,6 ring protons of Tyr-75 were shifted 0.3 and 0.2
      ppm upfield, respectively, relative to their positions in small peptides,
      indicating significant shielding and/or hydrogen bonding. The Tyr-75 ring proton
      signals narrowed slightly, with no discernible change in chemical shift, on
      conversion from dimer to monomer in the unliganded state. Ring protons of Tyr-49,
      distant from the monomer-monomer interface, but adjacent to the peptide-binding
      site, were markedly perturbed by dimerization, in accord with their behavior in
      bovine neurophysins. The results suggest that the secondary and tertiary
      structure of the region 75-78 is largely unchanged by dimerization, and argue
      against an important role for this region in dimerization-mediated conformational
      changes that alter the binding site in the unliganded state.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7822105
TI  - Structural and mechanistic implications of incorporating naturally occurring
      aberrant mutations of human dihydropteridine reductase into a rat model.
AB  - Phenylketonuria (PKU) is a debilitating hereditary disorder related to an
      individual's inability to convert phenylalanine to its usual tyrosine product.
      The genetic errors occur in three regions: in the cooperative enzymes
      phenylalanine hydroxylase (PAH) and dihydropteridine reductase (DHPR), and in the
      biosynthetic pathway from GTP to the hydroxylation cofactor, tetrahydrobiopterin
      (BH4). Many instances of naturally occurring defects in DHPR metabolism have been
      identified, and in most cases the error has been equated with an altered enzyme
      gene sequence. Using computer graphics, this report analyses the altered
      structural characteristics of eight of the enzymes encoded by mutant gene
      sequence and provides logical explanations for their diminished enzyme
      activities. In one instance, that of a threonine insertion, a mutant construct of
      the rat analog has been expressed in Escherichia coli and the DHPR isolated and
      characterised, confirming the marked changes this insert can create.

PMID- 7822106
TI  - Efficient Fmoc/solid-phase synthesis of Abu(P)-containing peptides using Fmoc
      Abu(PO3Me2)-OH.
AB  - The synthesis of the two 4-phosphono-2-aminobutanoyl-containing peptides, Leu-Arg
      Arg-Val-Abu(P)-Leu-Gly-OH.CF3CO2H and Ile-Val-Pro-Asn-Abu(P)-Val-Glu-Glu
      OH.CF3CO2H was accomplished by the use of Fmoc-Abu(PO3Me2)-OH in Fmoc/solid-phase
      peptide synthesis. The protected phosphoamino acid, Fmoc-Abu(PO3Me2)-OH, was
      prepared from Boc-Asp-OtBu in seven steps, the formation of the C-P linkage being
      effected by the treatment of Boc-Asa-OtBu with dimethyl trimethylsilyl phosphite.
      Peptide synthesis was performed using Wang Resin as the polymer support with both
      peptides assembled by the use of PyBOP for the coupling of Fmoc amino acids and
      20% piperidine for cleavage of the Fmoc group from the Fmoc-peptide after each
      coupling cycle. Cleavage of the peptide from the resin and peptide deprotection
      was accomplished by the treatment of the peptide-resin with 5% thioanisole/TFA
      followed by cleavage of the methyl phosphonate group by 1 M
      bromotrimethylsilane/1 M thioanisole in TFA.

PMID- 7822107
TI  - Comparative conformational analyses of mu-selective dermorphin and delta
      selective deltorphin-II in aqueous solution by 1H-NMR spectroscopy.
AB  - Two-dimensional 1H-NMR methods have been used to obtain complete proton resonance
      assignments and possible solution conformations of dermorphin (H-Tyr-D-Ala-Phe
      Gly-Tyr-Pro-Ser-NH2) and deltorphin-II (H-Tyr-D-Ala-Phe-Glu-Val-Val-Gly-NH2),
      naturally occurring mu- and delta-selective opioids, respectively, in order to
      examine the conformational characteristics that are closely related to the
      selectivities towards mu/delta-opioid receptors. With the use of the proton
      proton distances derived from ROESY measurements in aqueous solution, 50 possible
      3D structures are generated by means of distance geometry calculations. The
      conformers which satisfy the distance constraints and the torsion angles
      estimated from JNHC alpha H vicinal coupling constants within the allowable range
      are then subjected to molecular dynamics simulations for 10 ps after
      equilibration. Although dermorphin and deltorphin-II are both in equilibrium
      among many flexible conformers, some conformational differences are observed
      between these peptides: many conformers of dermorphin show a structure rounded at
      the N-terminal Tyr-D-Ala-Phe-Gly-Tyr and C-terminal Gly-Tyr-Pro-Ser-NH2 moieties,
      which are almost at right angles to each other, while those of deltorphin-II are
      characterized by a 'hook'-shaped backbone structure in which the nearly extended
      conformation of the Val-Val-Gly-NH2 sequence is located under the folded
      conformation of the N-terminal Tyr-D-Ala-Phe-Glu sequence. The possible
      relationship between these conformational characteristics and the mu/delta-opioid
      receptor selectivities is discussed.

PMID- 7822108
TI  - Recent advances in community psychiatry and psychosocial rehabilitation in Greece
      and the other southern European countries.
AB  - During the late 1960s and early 1970s community psychiatry and the transformation
      of psychiatric services was introduced in several Northern European countries. In
      Southern Europe, with the exception of Italy, changes in the mental health care
      delivery system regarding mental health legislation and decentralisation of
      services have only taken place since the mid-1980s. In this report several issues
      related to developments in institutional and community psychiatric care in
      Greece, Italy, Portugal and Spain are presented. A comparison is provided between
      some socioeconomic and psychiatric morbidity indicators and the availability of
      alternative community based care and rehabilitation in these countries.

PMID- 7822109
TI  - Psychopathology and long-term adjustment after crises in refugees from East
      Germany.
AB  - OBJECTIVE: In this study we examined psychopathology, diagnoses, social
      adjustment and the course of symptoms over two and a half years in East German
      refugees who suffered a crisis immediately after migrating to West Berlin just
      prior to or shortly after the breaching of the Wall in autumn 1989. METHODS: One
      hundred and twenty two refugees seeking crisis intervention in a psychiatric
      outpatient unit after arrival were investigated. Six months later 59% and two and
      a half years after migration 30% of the patients were re-examined. RESULTS: The
      patients had been exposed to prolonged stress situations in East Germany and were
      suffering from anxious-depressive syndrome with vegetative complaints. Sixty
      patients required more than one crisis intervention during the first six months
      after resettlement. During the follow-up period symptoms decreased significantly.
      At the second follow-up interview 81% of the patients had a satisfactory job, and
      89% acceptable accommodation. CONCLUSIONS: Satisfactory classification of the
      psychiatric disorders induced in East German refugees by prolonged stress was not
      possible according to the DSM-III-R criteria. Initial crises are not necessarily
      associated with poor long-term adjustment after migration.

PMID- 7822110
TI  - Relationship of migrant status (refugee or immigrant) to mental health.
AB  - This study investigated and compared mental health levels among refugees and
      immigrants living in New Zealand. One hundred and twenty-nine Indochinese
      refugees, 57 Pacific Island immigrants and 63 British immigrants to New Zealand
      were surveyed. A questionnaire and the Hopkins Symptom Checklist-25 (HSCL-25) in
      English and in three Indochinese translations, were administered face-to-face.
      The hypothesis that migrant status (being a refugee or immigrant) affects mental
      health and that refugees experience more emotional distress than immigrants was
      only supported by the comparison with British immigrants. Both Indochinese
      refugees and Pacific Island immigrants experienced relatively low levels of
      mental health. However, the incidence of clinical depression and clinical total
      emotional distress tended to be higher among Indochinese refugees than in either
      immigrant group. In contrast clinical anxiety occurred most often among Pacific
      Islanders.

PMID- 7822111
TI  - Cultural sensitivity: ICD-10 versus DSM-III-R.
AB  - This article is the outcome of a comparison of the ICD-10 (International
      Classification of Diseases, 10th Revision) and DSM-III-R (Diagnostic and
      Statistical Manual, Third Edition, Revised). The study indicates that the ICD-10
      has made great progress in widening the international scope of contemporary
      systems of classification in psychiatry and that the inclusion of certain
      cultural elements into a classificatory system could enrich its worldwide
      perspective.

PMID- 7822112
TI  - Asians presenting to a sex and marital therapy clinic.
AB  - This paper presents the findings of a retrospective analysis of the clinic
      registration forms and case files of Asian attenders of a sex and marital
      problems clinic over a three year period. An age/sex matched English control
      group was selected for comparison. Diagnoses, presenting patient complaints,
      sociodemographic characteristics, time between referral and first attendance and
      outcome of therapy were examined. Our samples of Asian and English attenders of
      equal educational and occupational status, when examined as two populations, did
      not differ in terms of diagnoses, sociodemographic characteristics, time from
      referral to first attendance and outcome of therapy. Differences in presenting
      complaints reflected individual unique evaluations of changed sexual functioning.
      There were, however, clearly problems for the Asian group related to differences
      of language and culture. It may be that our population of Asians was too
      heterogenous to enable a valid demonstration of these differences between English
      and Asian samples.

PMID- 7822113
TI  - Effect of psychiatric labels on attitudes toward mental illness in a Turkish
      sample.
AB  - The influence of specific psychiatric labels and types of psychopathology on
      various attitudes were investigated in a sample (N = 84) of visitors of patients
      in a Turkish hospital. Vignettes representing two types of psychopathology with
      and without labels were used as the stimulus material and the attitudes toward
      those descriptions were assessed with the use of a questionnaire. Statistical
      analyses showed that labels had significant influence on recognition of mental
      illness, social distance, expected physical burden, and perception of treatment
      necessity. Type of psychopathology significantly influenced recognition of mental
      illness, social distance, expected physical burden, prognosis, and treatment
      choice. The results were discussed within the context of previous findings and
      the need for research pointed out.

PMID- 7822114
TI  - The eating attitudes and behaviours of Asian and British schoolgirls: a pilot
      study.
AB  - This study set out to examine dietary, weight and eating attitudes of 12-18 year
      old British and Asian girls. Ninety-six subjects from a state school completed
      the Eating Attitudes Test (EAT-26), the Binge Eating Questionnaire (BEQ) and a
      questionnaire concerning the perceived level of integration into British society.
      The mean EAT-26 score was higher than any other study has found using a school
      population. No significant correlation was found between age and EAT-26 score,
      and there was no significant difference between the Asian and British mean EAT-26
      scores. The EAT-26 scores were not significantly higher in girls from families of
      higher socioeconomic class compared to those from lower socioeconomic class.
      There was however some support for the prediction that resentment in the Asian
      girls was expressed in higher EAT-26 scores. No significant group difference was
      found between Asian and British girls with regard to vomiting behaviour. The
      results are discussed in terms of the literature on eating disorders.

PMID- 7822115
TI  - Needs not diagnosis.

PMID- 7822116
TI  - Ca2+, N-methyl-D-aspartate receptors, and AIDS-related neuronal injury.

PMID- 7822117
TI  - The role of the amygdala in emotional learning.

PMID- 7822118
TI  - Excitotoxicity and neurological disorders: involvement of membrane phospholipids.
AB  - Excitatory amino acids and their receptors play an important role in membrane
      phospholipid metabolism. Persistent stimulation of excitatory amino acid
      receptors by glutamate may be involved in neurodegenerative diseases and brain
      and spinal cord trauma. The molecular mechanism of neurodegeneration induced by
      excitatory amino acids is, however, not known. Excitotoxin-induced calcium entry
      causes the stimulation of phospholipases and lipases. These enzymes act on neural
      membrane phospholipids and their stimulation results in accumulation of free
      fatty acids, diacylglycerols, eicosanoids, and lipid peroxides in
      neurodegenerative diseases and brain and spinal cord trauma. Other enzymes, such
      as protein kinase C and calcium-dependent proteases, may also contribute to the
      neuronal injury. Excitotoxin-induced alterations in membrane phospholipid
      metabolism in neurodegenerative diseases and neural trauma can be studied in
      animal and cell culture models. These models can be used to study the molecular
      mechanisms of the neurodegenerative processes and to screen the efficacy of
      therapeutic drugs.

PMID- 7822119
TI  - Processing of Alzheimer A beta-amyloid precursor protein: cell biology,
      regulation, and role in Alzheimer disease.

PMID- 7822120
TI  - Injury-related behavior and neuronal plasticity: an evolutionary perspective on
      sensitization, hyperalgesia, and analgesia.

PMID- 7822121
TI  - Molecular neurobiology of the GABAA receptor.

PMID- 7822123
TI  - [Value of imaging procedures in diagnosis of arrhythmia].

PMID- 7822122
TI  - The pharmacology and function of central GABAB receptors.
AB  - In conclusion, GABAB receptors enable GABA to modulate neuronal function in a
      manner not possible through GABAA receptors alone. These receptors are present at
      both pre- and postsynaptic sites and can exert both inhibitory and disinhibitory
      effects. In particular, GABAB receptors are important in regulating NMDA receptor
      mediated responses, including the induction of LTP. They also can regulate the
      filtering properties of neural networks, allowing peak transmission in the
      frequency range of theta rhythm. Finally, GABAB receptors are G protein-coupled
      to a variety of intracellular effector systems, and thereby have the potential to
      produce long-term changes in the state of neuronal activity, through actions such
      as protein phosphorylation. Although the majority of the effects of GABAB
      receptors have been reported in vitro, recent studies have also demonstrated that
      GABAB receptors exert electrophysiological actions in vivo. For example, GABAB
      receptor antagonists reduce the late IPSP in vivo and consequently can decrease
      inhibition of spontaneous neuronal firing following a stimulus (Lingenhohl and
      Olpe, 1993). In addition, blockade of GABAB receptors can increase spontaneous
      activity of central neurons, suggesting the presence of GABAB receptor-mediated
      tonic inhibition (Andre et al., 1992; Lingenhohl and Olpe, 1993). Despite these
      electrophysiological effects, antagonism of GABAB receptors has generally been
      reported to produce few behavioral actions. This lack of overt behavioral effects
      most likely reflects the modulatory nature of the receptor action. Nevertheless,
      two separate behavioral studies have recently reported an enhancement of
      cognitive performance in several different animal species following blockade of
      GABAB receptors (Mondadori et al., 1992; Carletti et al., 1993). Because of their
      small number of side effects, GABAB receptor antagonists may represent effective
      therapeutic tools for modulation of cognition. Alternatively, the lack of overt
      behavioral effects of GABAB receptors may indicate that these receptors are more
      important in pathologic rather than normal physiological states (Wojcik et al.,
      1989). For example, a change in receptor affinity or receptor number brought on
      by the pathology could enhance the effectiveness of GABAB receptors. Of
      significance, CGP 35348 has been shown to block absence seizures in genetically
      seizure prone animals, while inducing no seizures in control animals (Hosford et
      al., 1992; Liu et al., 1992). Thus, GABAB receptors may represent effective sites
      for pharmacological regulation of absence seizures. Perhaps further behavioral
      effects of these receptors will become apparent only after additional studies
      have been performed using the highly potent antagonists that have been recently
      introduced.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7822124
TI  - [Imaging methods in cardiology. Heart failure (acute, chronic)].

PMID- 7822125
TI  - [Imaging methods in hypertensive heart disease].

PMID- 7822126
TI  - [Imaging methods in cardiology. Acute and chronic pulmonary hypertension].

PMID- 7822127
TI  - [Imaging methods in cardiology. Coronary heart disease].

PMID- 7822128
TI  - [Cyanosis and hourglass nails in chronic liver disease].

PMID- 7822129
TI  - [40-year-old Turkish patient with spinal epidural tumor and sacroiliitis].

PMID- 7822130
TI  - [Does hyperbilirubinemia in Meulengracht disease (Gilbert syndrome) need
      treatment?].

PMID- 7822131
TI  - [Pruritus in internal diseases].

PMID- 7822132
TI  - [Response to the letter by K. Kochsiek, Wurzburg].

PMID- 7822133
TI  - [Imaging methods in the diagnosis of congenital heart defects].

PMID- 7822134
TI  - [Imaging methods in acquired heart valve defects].

PMID- 7822135
TI  - [Imaging procedures in diagnosis of aortic dissection].

PMID- 7822136
TI  - Endotoxin-induced uveitis and nitrous oxide.

PMID- 7822137
TI  - The roles of bicarbonate and CO2 in transendothelial fluid movement and control
      of corneal thickness.
AB  - PURPOSE: To determine whether maintenance of corneal hydration is dependent on
      bicarbonate ions and whether these ions can be derived from metabolic or
      exogenous CO2, and to investigate the relationship of transendothelial fluid
      movement to control of hydration. METHODS: The thickness of intact or
      deepithelialized rabbit corneas was measured while superfused on the endothelial
      surface with either 33 mM HGO3-/5% CO2 buffered media or 10 mM HPO4- buffered
      media in the presence and absence of inhibitors of ion transport and respiration.
      The corneal surface was covered with either silicone oil ("normal" corneas) or
      with the same media used for superfusion ("swollen" corneas). ATP and Na+,K(+)
      ATPase activity were measured in endothelia scraped from the tissues after
      superfusion. RESULTS: Intact and deepithelialized corneas covered with oil
      swelled at a negligible rate (4 to 8 microns/hour) in 33 mM HCO3- medium but at
      45 to 60 microns/hour in HPO4- medium. Antimycin A altered neither of these
      swelling rates, but ethoxzolamide (0.1 mM) caused swelling in HCO3-/CO2
      (approximately 12 microns/hour above controls) with no change of rate in HPO4-.
      Ouabain (0.1 mM) increased swelling to 45 to 50 microns/hour in HCO3-/CO2 but had
      no effect in HPO4-. Saturating the oil on deepithelialized corneas with 5% CO2,
      or putting HCO3-/CO2 medium on the epithelial surface of intact corneas, did not
      alter the swelling rates seen with HPO4- superfusion. The equilibrium thickness
      of deepithelialized corneas swollen with HCO3-/CO2 on both surfaces was 35
      microns less than that of corneas swollen in HPO4-. The difference was abolished
      by ouabain, which caused corneas in HCO3-/CO2 to swell an additional 30 microns
      but did not alter the equilibrium thickness of corneas swollen in HPO4-.
      Ethoxzolamide and DIDS (0.2 mM) increased the thickness in HCO3-/CO2 but not in
      HPO4-. Na+,K(+)-ATPase activities of endothelia were similar after HCO3-/CO2 and
      HPO4- superfusions, but the concentration of ATP in the HPO4(-)-superfused
      tissues was increased 35%. CONCLUSIONS: Normal corneal thickness can be
      maintained in vitro only in media that contain HCO3- at concentrations of more
      than 20 mM. Neither metabolic CO2 nor CO2 present in air-equilibrated, nominally
      HCO3(-)-free media can supply this requirement for HCO3-, even though these
      sources support the presumably related processes of transendothelial fluid
      movement and intracellular pH regulation.

PMID- 7822138
TI  - Potassium conductances in cultured bovine and human retinal pigment epithelium.
AB  - PURPOSE: To identify K+ conductances on the apical and basolateral membranes in
      cultured monolayers of fetal bovine and human retinal pigment epithelium (RPE).
      METHODS: Bovine and human RPE cells were grown on a permeable substrate for an
      average of 4 and 25 months, respectively, mounted in a modified Ussing chamber
      that allowed rapid solution changes at both membranes, and perfused with modified
      Ringer's solutions. Conventional microelectrode recording techniques were used to
      record intracellularly from RPE cells. RESULTS: Electrical parameters under
      control conditions for bovine (n = 11) and human (n = 7) cultures respectively,
      were: transepithelial potential, 0.6 +/- 0.2 and 3.2 +/- 0.5 mV; Rt, 70 +/- 12
      and 227 +/- 30 ohm.cm2; and Vap, -61 +/- 3 and -51 +/- 2 mV (mean +/- SEM). The
      relative K+ conductance (TK) was estimated from responses to 10-fold increases in
      [K+]o. For the apical and basal membranes, the values for TK were 0.65 and 0.37,
      respectively, in bovine and 0.33 and 0.45, respectively, in human RPE. Barium
      applied to either surface of the cultures produced membrane depolarizations and
      suppressed the responses significantly to K+. In bovine, a 10-fold decrease in
      basal [K+]o hyperpolarized Vba by 2 +/- 1 mV; a similar decrease in apical [K+]o
      hyperpolarized Vap by 14 +/- 1 mV. At both membranes, perfusion with Ba2+
      unmasked a significant membrane depolarization induced by lowering [K+]o; this
      phenomenon, observed previously at the apical membrane in fresh explant bovine,
      frog, and toad RPE, appears to be an unmasking of Na+/K+ pump modulation by K+.
      CONCLUSIONS: These results indicate the presence of Ba2+ sensitive K+
      conductances at the apical and basal membranes of confluent monolayers of
      cultured fetal human and bovine RPE and the presence of Na+/K+ pump sites at both
      membranes of cultured bovine cells.

PMID- 7822139
TI  - Quantitative evaluation of leukocyte dynamics in retinal microcirculation.
AB  - PURPOSE: Leukocyte rheology may play a key role in microcirculation because
      leukocytes have unique properties, such as large cell volume, high cytoplasmic
      rigidity, and low deformability. However, only a few methods are available to
      study the dynamic behavior of leukocytes in retinal microcirculation. The authors
      developed a new method to analyze directly movements of leukocytes in the retinal
      vessels of primates. METHODS: Acridine orange, which has been used as a nuclear
      stain in histochemistry and cytochemistry, was injected intravenously into
      cynomolgus monkeys for a vital staining of leukocytes. The fundus image was
      generated with the argon blue laser and a scanning laser ophthalmoscope. The
      images were recorded on a magnetic tape and evaluated with a personal computer
      based image analysis system. RESULTS: Each leukocyte was recognized as a single
      fluorescent dot moving in the retinal vessels. It was possible to analyze the
      spatial and temporal dynamics of individual leukocytes in the capillaries. Some
      leukocytes passed through the capillaries, plugging transiently under the
      physiological condition. Leukocytes that stayed in the same position for a few
      minutes may have stuck to the endothelium as a result of leukocyte-endothelial
      interactions. In the postcapillary vessels, leukocytes tended to be displaced
      from the center stream toward the vessel walls. The mean flow velocity of
      leukocytes in the perifoveal capillary was 0.92 +/- 0.32 mm/sec. CONCLUSIONS:
      This study clearly demonstrated that rheologic behaviors of leukocytes in the
      retinal microcirculation can be studied through the vital staining with acridine
      orange in vivo. The authors' results suggest a potential role of leukocytes in
      retinal vascular flow disturbances. This study may open the door to the
      investigation of leukocyte hemodynamics in the retinal microcirculation in vivo.

PMID- 7822140
TI  - Perfluorinated organic liquid as an intraocular oxygen reservoir for the ischemic
      retina.
AB  - PURPOSE: Liquid perfluorocarbons are used as temporary vitreous substitutes in
      the surgical management of complicated retinal detachment. The purpose of this
      study was to determine if physiologic benefits could also be derived from the
      high oxygen solubility of perfluorochemicals relative to vitreous, especially
      during retinal ischemia. METHODS: The normal vitreous humor of the rabbit eye was
      replaced with either perfluorotributylamine (FTBA) or balanced salt solution
      (BSS). Retinal ischemia was then induced by increasing the intraocular pressure
      above the peak systolic blood pressure for intervals of 10, 30, or 90 minutes.
      RESULTS: Over a 10- or 30-minute period of ischemia, during which
      electroretinographic (ERG) responses were recorded, FTBA-filled eyes and BSS
      filled eyes showed decreases in the a- and b-wave amplitudes. However, wave
      amplitudes were significantly greater in FTBA-filled eyes at most times examined
      (P < .05). ERG responses were maintained throughout a 30-minute ischemic interval
      in oxygenated FTBA-filled eyes, but not in oxygenated BSS- or deoxygenated FTBA
      filled eyes. When examined 1 day after a 90-minute interval of ischemia,
      oxygenated FTBA-filled eyes maintained 45% and 57% of the preischemic ERG a- and
      b-wave amplitudes, respectively, compared to a 5% and 3% retention of wave
      amplitudes in oxygenated BSS-filled eyes. On light microscopic examination of
      these eyes, FTBA-exposed retinas showed less ischemic damage than BSS-exposed
      retinas. CONCLUSIONS: When used as a vitreous substitute, FTBA exerts a
      neuroprotective effect on the ischemic retina that appears to relate to an
      increased retinal oxygen supply compared to BSS.

PMID- 7822141
TI  - Novel human ocular glutathione S-transferases with high activity toward 4
      hydroxynonenal.
AB  - PURPOSE: To study the distribution and expression of glutathione S-transferase
      isozymes involved in detoxification of endogenously generated toxic products of
      lipid peroxidation, namely, 4-hydroxynonenal (4-HNE) in human lens, retina,
      cornea, iris, ciliary body and to study their kinetic and structural properties.
      METHODS: The authors have previously cloned and sequenced cDNA of mouse mGSTA4-4,
      which shows high activity towards 4-HNE. They have expressed it in Escherichia
      coli and have raised antibodies against the recombinant mGSTA4-4. In the present
      study, these antibodies were used in Western blot analysis and immunoaffinity
      chromatography to study the expression and to purify the human ortholog(s) of
      mGSTA4-4 from ocular tissues. RESULTS: Western blot analyses of human ocular
      tissues indicated that a glutathione S-transferases (GST) isozyme immunologically
      similar to mGSTA4-4 was expressed in cornea, retina, and iris and ciliary body,
      but not in lens. This isozyme designated as hGST 5.8 was purified to homogeneity
      from human retina, cornea, and iris and ciliary body by immunoabsorption on
      immobilized antibodies against mGSTA4-4. The human ortholog of mGSTA4-4,
      designated as hGST 5.8 purified from all these tissues and pI value of 5.8,
      subunit Mr value of 25 k and blocked N-terminal. Amino acid sequences of CNBr
      fragments of hGST 5.8 isozymes of human ocular tissues showed a high degree of
      primary structure homologies with the corresponding regions of mGSTA4-4. There
      were noticeable differences in the amino acid sequences of hGST 5.8 of cornea,
      retina, and iris and ciliary body, suggesting the presence of several closely
      related hGST 5.8 subunits in the ocular tissues. This heterogeneity was due to
      tissue-specific expression rather than simple allelic polymorphism. The hGST 5.8
      had about sixfold to eightfold higher activity toward 4-hydroxynonenal than 1
      chloro-2,4-dinitrobenzene, or CDNB. The catalytic efficiency (Kcat/Km) of ocular
      hGST 5.8 for 4-HNE was about 100-fold higher than those for the alpha, mu, or pi
      classes of GST. In addition, hGST 5.8 expressed glutathione peroxidase activity
      toward phospholipid hydroperoxides and GSH-conjugating activity toward 9,10-epoxy
      stearic acid. CONCLUSIONS: The results indicate that hGST 5.8 isozyme(s) distinct
      from the alpha, mu, and pi classes of GSTs, are differentially expressed in human
      ocular tissues and may play an important role in protective mechanisms against
      endogenous toxicants generated during lipid peroxidation.

PMID- 7822142
TI  - A corneal epithelial inhibitor of stromal cell collagenase synthesis identified
      as TGF-beta 2.
AB  - PURPOSE: To determine the molecular mechanisms whereby substances released by
      corneal epithelial cells act to inhibit the elaboration of collagenolytic
      activity by corneal stromal cells and to determine whether inhibitory activity
      might be mediated by interleukin-1 receptor antagonist (IL-1ra) or transforming
      growth factor (TGF)-beta. METHODS: Conditioned media were generated from primary
      cultures of rabbit corneal epithelial cells, from passaged cultures of rabbit
      corneal stromal fibroblasts, and from cells of the rabbit corneal epithelial cell
      line, SIRC. Pure populations of stromal cells were isolated from rabbit cornea
      and used directly for bioassay of the conditioned media to detect substances that
      inhibit collagenase synthesis. The mink lung epithelial cell line, Mv1Lu, was
      used for bioassay of TGF-beta-like activity. The addition of specific
      neutralizing antisera to bioassays allowed an assessment of the contribution of
      each isoform to the net regulatory activity. Reverse transcription-polymerase
      chain reaction and Northern blot analysis were employed to detect the presence of
      IL-1ra or TGF-beta mRNA species in cells from cultures used to generate
      conditioned media. RESULTS: Both stimulatory and inhibitory substances that
      regulate the synthesis of stromal cell collagenase are released by corneal
      epithelial cells in primary culture. In contrast, only stimulatory activity is
      produced by corneal fibroblasts or SIRCs. MRNAs for a TGF-beta isoform, TGF-beta
      2, and IL-1ra were identified in epithelial cells. Stromal fibroblasts also
      expressed TGF-beta 2 mRNA, but no evidence was found for expression of TGF-beta 3
      mRNA in any of the three cell types. TGF-beta 2 is released by epithelial cells
      in both active and latent forms. This cytokine mediates the major portion of the
      net inhibitory activity against stromal cell collagenase synthesis produced by
      corneal epithelial cells. CONCLUSIONS: This study demonstrates the expression of
      TGF-beta 2 and IL-1ra by corneal epithelial cells in culture. It is the TGF-beta
      2 that acts as the major inhibitor of collagenase synthesis by corneal stromal
      cells in culture. However, IL-1ra and TGF-beta 2 are likely to play important
      roles in epithelial-mesenchymal interactions regulating corneal development,
      homeostatic maintenance, and repair.

PMID- 7822143
TI  - Characterization of arachidonic acid metabolism and the polymorphonuclear
      leukocyte response in mice infected intracorneally with Pseudomonas aeruginosa.
AB  - PURPOSE: To examine the activity of myeloperoxidase (MPO) and the concentrations
      of the proinflammatory metabolites of arachidonic acid (AA) in ocular tissue of
      mice that are either capable or incapable of restoring corneal clarity during an
      intraocular Pseudomonas aeruginosa infection. METHODS: For a period of 11 days
      after infection, whole eyes were enucleated and homogenized in buffer from mice
      given only an initial infection as well as from mice given a subsequent infection
      in the previously uninfected eye either 4 or 8 weeks after the initial infection.
      Tissue-free supernatants from the ocular homogenates were used for the
      determination of MPO activity by quantitating the conversion of specific
      substrate by spectrophotometric methods and for the quantitation of AA
      metabolites by ELISA: RESULTS: Overall, animals reinfected at 4 and 8 weeks had a
      lower inflammatory response when compared to the mice given only the initial
      infection. The lowest levels of LTB4 and MPO activity, indicators of PMN
      involvement, were observed in the the 8-week reinfected mice, which restored
      corneal clarity in an enhanced manner. CONCLUSIONS: These results suggest that
      induced ocular PMN responses may play a role, in part, in the inflammatory
      response leading to the tissue destruction observed during ocular P. aeruginosa
      infection.

PMID- 7822144
TI  - Rod outer segment-associated N-acetylgalactosaminylphosphotransferase.
AB  - PURPOSE: To determine the exact location of a cell surface glycosyltransferase (N
      acetylgalactosaminylphosphotransferase, (GalNAcPTase) immunochemically identified
      in mammalian rod outer segments (ROS), to determine whether anti-GalNAcPTase
      antibody recognizes retinal molecules that possess transferase activity and to
      characterize ROS transferase enzyme activity and acceptors. The GalNAcPTase is
      known to be associated with the adhesion molecule N-cadherin in embryonic avian
      retinas and with E-cadherin in mammalian pancreatic islet cells. METHODS:
      Purified, fixed ROS were reacted with anti-chick GalNAcPTase antibody followed by
      secondary antibody conjugated to colloidal gold and were examined by electron
      microscopy. Fractions of retinal and ROS proteins enriched in the transferase
      were obtained through batch adsorption on Sepharose, separated by gel
      electrophoresis, transferred to nitrocellulose, and either reacted with anti
      GalNAcPTase antibody or assayed for transferase activity. Interphotoreceptor
      matrix (IPM) was examined for the presence of immunoreactive GalNAcPTase by gel
      electrophoresis and immunoblot. The kinetics and endogenous acceptors of the cow
      ROS transferase were characterized. RESULTS: ROS are specifically labeled by anti
      GalNAcPTase antibody at the cell surface. The immunogold label was associated
      with the cell surface and with flocculent material adherent to the cell surface.
      In addition, soluble and particulate fractions of the IPM showed GalNAcPTase-like
      immunoreactivity. The transferase appears as single immunoreactive band at or
      near 220 kd. Transferase enzyme activity was present at this position on Western
      transfers of retinal and ROS proteins. In whole ROS, transferase activity was
      directed toward endogenous acceptors of very high molecular mass. CONCLUSIONS:
      The GalNAcPTase is localized on ROS in association with the cell surface and with
      components of the IPM. The molecule recognized by the anti-GalNAcPTase antibody
      possesses transferase activity toward itself and a few other proteins, but mostly
      toward very large molecules that may be IPM proteoglycans. It is not yet known
      whether the enzyme of the adult retina specifically transfers sugar or sugar
      phosphate groups to its acceptors. It is proposed that the ROS GalNAcPTase is
      involved in the modulation of adhesive phenomena between or within photoreceptors
      or between photoreceptors and the interphotoreceptor matrix.

PMID- 7822145
TI  - A quantitative system to evaluate diabetic retinopathy from fundus photographs.
AB  - PURPOSE: To evaluate a quantitative system to measure the early lesions of
      diabetic retinopathy seen in stereoscopic fundus photographs. METHODS: Using a
      quantitative classification system, photographs of 4657 eyes (7 stereo pairs of
      35-mm slides per eye) were scored for 16 diabetic lesions. A single severity
      level (identical to the ETDRS Interim Scale) was calculated for each eye. The
      reliability of this technique, and its reproducibility by independent examiners,
      was evaluated for individual lesions and severity levels using percent agreement,
      kappa, and weighted kappa statistics. RESULTS: This quantitative technique
      demonstrated an "almost perfect" agreement (weighted kappa > or = 0.810) on all
      but one lesion by independent observers. For the severity levels, there was a
      95.7% perfect agreement (kappa = 0.9428). The reproducibility of agreement over
      time was "almost perfect" on all but four lesions; with 88% perfect agreement
      (kappa = 0.8394) for severity levels. CONCLUSIONS: When used to evaluate the
      early lesions of diabetic retinopathy, the Vanderbilt Classification System is
      highly reliable between graders and over time. This system can gather
      quantitative data and evaluate incremental changes in an accurate, reproducible
      manner.

PMID- 7822146
TI  - The relationship of age-related maculopathy, cataract, and glaucoma to visual
      acuity.
AB  - PURPOSE: To investigate the relationship of age-related maculopathy, cataract,
      and glaucoma to visual acuity in the population-based Beaver Dam Eye Study.
      METHODS: A cross-sectional, population-based study was performed in people 43
      through 86 years of age residing in Beaver Dam, Wisconsin, who were identified
      between 1987 and 1988 and examined (n = 4926) between 1988 and 1990. Of those who
      participated, 99.4% were white. Visual acuity was measured (n = 4886) using a
      modification of the Early Treatment Diabetic Retinopathy Study protocol.
      Stereoscopic color fundus photographs and slit lamp and retroillumination
      photographs of the lens were graded in a masked fashion using standardized
      protocols to determine the presence of age-related maculopathy and central
      cataract. RESULTS: Fifty-seven percent of those who were legally blind had late
      age-related maculopathy in both eyes. The frequency of visual acuity of 20/200 or
      worse was not significantly different in eyes with exudative macular degeneration
      (48%) than in eyes with pure geographic atrophy (42%). While controlling for
      other factors (age, central cataract, and glaucoma) in participants with both
      gradable age-related maculopathy and visual acuity measurable in at least one eye
      (n = 4716), investigators found that each of the early age-related maculopathy
      lesions was associated with a decrease in visual acuity of approximately two
      letters or fewer when compared to eyes without these lesions. Late age-related
      maculopathy was associated with a decrease of approximately seven lines of
      letters read correctly. CONCLUSION: These data demonstrate that exudative macular
      degeneration and pure geographic atrophy are the most important causes of legal
      blindness in this population and that early age-related maculopathy, central
      cataract, and glaucoma had a small effect on visual acuity.

PMID- 7822147
TI  - Primary open-angle glaucoma is not associated with photoreceptor loss.
AB  - PURPOSE: To determine if photoreceptors die in primary open-angle glaucoma.
      METHODS: Retinas were examined in a masked fashion from nine standard locations
      of 14 eyes with documented open-angle glaucoma and from nine age-matched control
      eyes. The number and density of photoreceptors, as well as the area and height of
      the outer nuclear layer, were calculated with an automated image analysis system.
      The number of photoreceptors per 0.1 mm of retina was determined. RESULTS: No
      significant difference was seen between control and glaucomatous eyes in
      comparisons of photoreceptor density, outer nuclear layer height, or
      photoreceptors per 0.1 mm of retinal length in nine retinal zones. There was no
      detectable association between photoreceptor number and severity of glaucoma
      (defined as mild, moderate, or severe), visual field, and optic nerve fiber loss.
      In eyes in which damage predominated in the upper or lower visual field, no
      corresponding difference in photoreceptor number in upper compared to lower
      retinal zones was observed. CONCLUSION: Photoreceptors are not lost in
      substantial numbers in primary open-angle glaucoma.

PMID- 7822148
TI  - Cloning and in situ hybridization of rabbit decorin in corneal tissues.
AB  - PURPOSE: To develop molecular probes and to identify the cell types responsible
      for decorin synthesis in healing cornea. METHODS: Adult rabbit cornea and rabbit
      corneal stromal cell (keratocyte) culture cDNA libraries were constructed. The
      libraries were screened with commercially available human cDNA and
      oligonucleotide probes. Positive clones were sequenced to obtain a full length
      rabbit decorin cDNA. Synthetic oligonucleotides for rabbit decorin were chosen as
      probes for Northern blot analysis and in situ hybridization of healing rabbit
      corneas. RESULTS: The cDNA sequences of the positive clones from the two
      libraries were identical in areas of overlap. The combined cDNA sequence
      indicated a 1.5-kb length with a complete open reading frame for decorin. The
      cDNA and deduced amino acid sequences are 90% and 88% identical, respectively, to
      previously reported human fibroblast and bovine bone decorin sequences. A
      hypervariable region near the N-terminal has little homology to decorins of other
      species or other rabbit protein. Northern blot analysis detected a 2.0-kb and a
      2.3-kb band in mRNA from rabbit keratocyte cultures. Decorin mRNA was detected in
      keratocytes of normal and healing rabbit corneas by in situ hybridization. Label
      in the healing tissue was markedly increased above normal. Normal endothelium and
      epithelium in normal and healing cornea failed to show label. CONCLUSIONS:
      Decorin mRNA from normal adult rabbit cornea is identical to decorin mRNA from
      keratocytes in culture and is highly homologous to decorin from other animal
      species. In situ hybridization indicated an upregulation of decorin message in
      cells adjacent to and within the healing tissue. Both stroma-derived and
      endothelium-derived cells in the wound synthesize message for decorin.

PMID- 7822149
TI  - Hypophysectomy-induced regression of female rat lacrimal glands: partial
      restoration and maintenance by dihydrotestosterone and prolactin.
AB  - PURPOSE: Previous studies have implicated androgens and one or more as yet
      unknown pituitary or pituitary-dependent factors in the regulation of certain
      lacrimal gland functions. Many observations suggest that prolactin (PRL) might
      well be one of these factors. This study was designed to determine the effect of
      hypophysectomy on biochemical markers of exorbital lacrimal gland secretory
      capacity and to determine the extent to which dihydrotestosterone (DHT) and
      prolactin reverse these changes. METHODS: Female rats were hypophysectomized and,
      5 days later, were treated for 2 days with DHT (0.25 or 1 mg/kg), PRL (1 or 5
      mg/kg), combinations of the low or high doses of DHT and PRL, or vehicle only.
      The animals were killed, and crude membrane fractions were isolated from their
      lacrimal glands. An untreated group served as control. RESULTS: Lacrimal glands
      atrophied rapidly after hypophysectomy, losing 40% of their total and membrane
      associated protein and 50% of their total DNA within 5 days. Total Na+,K(+)
      ATPase and acid phosphatase activities and beta-adrenergic receptor number were
      decreased by half, whereas alkaline phosphatase activity and muscarinic
      cholinergic receptor number were reduced by 25% to 30%. DHT treatment increased
      total DNA above control values; it partially restored the amount of protein in
      the gland, the Na+,K(+)-ATPase and acid phosphatase activities, and the beta
      adrenergic receptor number; and it fully restored the alkaline phosphatase
      activity. Prolactin treatment partially restored the amount of protein in the
      gland and the Na+,K(+)-ATPase activity; it fully restored the alkaline
      phosphatase activity and cholinergic receptor number; but it had no effect on the
      acid phosphatase activity or the beta-adrenergic receptor number. The high dose
      of DHT reduced the increase in cholinergic receptor number elicited by PRL. The
      high dose of PRL reduced the increases of total Na+,K(+)-ATPase and acid
      phosphatase elicited by DHT. CONCLUSIONS: These findings suggest that DHT and PRL
      exert general trophic actions on the lacrimal gland and specifically on lacrimal
      Na+,K(+)-ATPase, acid phosphatase, and neurotransmitter receptors. They also
      suggest that excessive levels of either hormone may be deleterious to secretory
      function. Because sex hormone levels are prone to wide fluctuations in women, our
      results also suggest a plausible hypothesis to account for the greater incidence
      in women of lacrimal insufficiency.

PMID- 7822150
TI  - Evidence for a major gene for cortical cataract.
AB  - PURPOSE: To examine the possible presence of a major gene determining
      susceptibility to cortical cataract. METHODS: The percentage of the lens area
      involved with cortical opacity, summed over both eyes, was evaluated in 1275
      individuals from the Beaver Dam Eye Study. After adjusting for the effects of age
      and sex, these measures of cortical cataract were subjected to sibling
      correlational analysis, commingling analysis, and segregation analysis. The Box
      and Cox power transformation was applied to the data for the commingling and
      segregation analyses. Using regressive models, four modes of transmission were
      examined, and under each mode three hypotheses and a general model were fitted by
      maximum likelihood and compared. RESULTS: Sister-sister and brother-brother
      correlations of the adjusted measures of cortical cataract are significant and
      similar; the brother-sister correlation is not significantly different either
      from these correlations or from zero. Two commingled distributions give the best
      fit to the data, especially after power transformation. Under each of four modes
      of transmission, the hypothesis that best fits the data is one in which there are
      only two distributions (and, hence, dominance under mendelian transmission), the
      power transformation parameter is fixed at the estimate obtained from commingling
      analysis, and there is residual sibling correlation. The data thus suggest the
      existence of a major effect for cortical cataract. Random environmental
      influences can be rejected as a cause of this major effect. Our analysis
      indicates the existence of a significant effect of sex on the residual variance.
      Allowing for this, the data suggest transmission of a single major gene, though
      this may not be the sole cause of the commingled distributions. CONCLUSIONS:
      Assuming a common variance for the two sexes, a single major gene can account for
      58% of the variability of age- and sex-adjusted measures of cortical cataract.
      With the variance sex dependent, a major gene can account for 75% and 45% of the
      total variability among males and females, respectively.

PMID- 7822151
TI  - Label-retaining cells are preferentially located in fornical epithelium:
      implications on conjunctival epithelial homeostasis.
AB  - PURPOSE: To determine the cell kinetic properties of epithelial cells from
      various zones of the conjunctiva. METHODS: The morphology and cell kinetics of
      bulbar, fornical, and palpebral conjunctival epithelium were studied in neonatal
      and adult SENCAR mice. To examine the proliferative rate of the conjunctival
      epithelium, a single administration of tritiated thymidine (3H-TdR) was used to
      detect cells in "S" phase. Proliferative rates were also assessed by determining
      mitotic activity after an intraperitoneal injection of colchicine to arrest cells
      in mitosis. To detect slow-cycling cells, mice received 3H-TdR continuously for 1
      week. After a 4-week chase, animals were sacrificed and eyes were surgically
      removed. All tissues were immediately fixed in formalin and processed for
      histology and autoradiography. RESULTS: Slow-cycling cells, detected as label
      retaining cells (LRCs), were identified in bulbar, fornical, and palpebral
      epithelia, as well as in limbal epithelium. The greatest number of LRCs was found
      in fornical epithelium. In addition, we found a number of label-retaining goblet
      cells. This cell population was shown to incorporate 3H-TdR after a single pulse
      administration, and mitotic figures were seen in goblet cells after colchicine
      treatment, indicating that conjunctival goblet cells have proliferative
      capabilities. CONCLUSIONS: These findings are consistent with earlier in vitro
      data that the fornical epithelium may be a zone enriched in conjunctival
      epithelial stem cells. This has important implications in conjunctival epithelial
      development and is relevant in wound repair. Furthermore, the concept that goblet
      cells are slow-cycling cells with proliferative capabilities provides new
      insights into the area of conjunctival homeostasis.

PMID- 7822152
TI  - Immunoreactivity against tau, amyloid precursor protein, and beta-amyloid in the
      human retina.
AB  - PURPOSE: Increased immunoreactivity (IR) of beta-amyloid and the amyloid
      associated proteins tau and amyloid precursor protein (APP) in the brain have
      been linked to the pathogenesis of neurodegenerative disorders such as
      Alzheimer's disease. However, the expression of these proteins has not been
      investigated in the normal or diseased human retina. METHODS: Using
      immunohistochemical techniques, we examined the distribution and age-related
      changes of anti-tau-1, anti-tau-2, anti-APP, and anti-beta-amyloid IR in the
      human retina at various ages (n = 24), in retinitis pigmentosa (RP, n = 6), and
      in age-related macular degeneration (ARMD, n = 10). RESULTS: Tau-1
      immunoreactivity was intense in the inner retinal layers and did not change with
      age or in RP. Eyes with ARMD showed less intense staining but exhibited a similar
      distribution. Tau-2 IR was faint and did not change with age but was mildly
      increased in the retinal pigment epithelium (RPE) of eyes with RP and in the
      retina of eyes with ARMD. APP IR was most prominent in the ganglion cell and
      nerve fiber layer, and it appeared to increase in ganglion cells of older persons
      and in RPE cells of eyes with RP and ARMD. Beta-amyloid IR was only detected
      focally in sub-RPE deposits in eyes from older persons. CONCLUSIONS: The proteins
      investigated in this study are present in the human retina. The staining pattern
      of tau is different from the brain, but it shows no age-related changes. The
      increased immunoreactivity of APP in retinal ganglion cells of older eyes and in
      RPE cells of eyes with RP and ARMD, as well as the patchy staining of beta
      amyloid within sub-RPE deposits, might indicate a relationship of these proteins
      to retinal aging and possibly to retinal degeneration in RP.

PMID- 7822153
TI  - Quantification of optic nerve blood flow changes using magnetic resonance
      imaging.
AB  - PURPOSE: To evaluate the possibilities of magnetic resonance imaging (MRI) for
      quantification of pharmacologically induced changes in optic nerve
      microcirculation. METHOD: T2-weighted MRI sequences were used to image the eye,
      optic nerve, and frontal cortex in rats. Two sets of control images before and
      one set during Gd (DTPA) infusion were recorded. Blood flow values for two
      regions of the optic nerve (an anterior part, including the optic nerve head, and
      a more posterior part) and the frontal cortex were calculated by image analysis
      from the change in signal intensity, as already reported for cerebral blood flow.
      For each rat, a control experiment before drug administration and a second
      experiment 30 minutes after subcutaneous injection of either placebo (n = 7),
      timolol (n = 7), or SDZ GLC-756, a dopamine D-1 antagonist and D-2 agonist (n =
      7), were carried out in a double-blind fashion. RESULTS: Mean basal blood flow
      values were found between 29.4 and 45.6 ml/100 g per minute in the anterior part
      of the optic nerve, 38.3 and 42.9 ml/100 g per minute in the posterior part of
      the optic nerve, and 68.0 and 75.0 ml/100 g per minute in the frontal cortex.
      Placebo and timolol did not cause significant changes. SDZ GLC-756 significantly
      increased blood flow by 238% +/- 65% in the anterior part and by 87% +/- 40% in
      the posterior part of the optic nerve. CONCLUSIONS: These results suggest that
      MRI provides quantification of optic nerve blood flow and that dopaminergic
      substances increase optic nerve blood flow.

PMID- 7822154
TI  - C-fos gene expression in rat retinal cells after focal retinal injury.
AB  - PURPOSE: To examine the expression of c-fos proto-oncogene in the rat retina
      after focal retinal injury. METHODS: A penetrating wound was made by pushing a 22
      gauge hypodermic needle through the retina into the vitreous. The retinas were
      analyzed by in situ hybridization using single-stranded RNA probes for c-fos
      transcripts and by immunocytochemistry using anti-S100 protein antibody. RESULTS:
      Thirty minutes after the penetrating wound, c-fos mRNA was expressed in the inner
      nuclear layer (INL) and the ganglion cell layer (GCL) of the retina.
      Immunocytochemistry before in situ hybridization demonstrated c-fos mRNA
      surrounding the S-100 protein immunoreactive cytoplasm in the middle layer of the
      INL. CONCLUSIONS: Focal retinal injury of the rat retina induced the expression
      of c-fos mRNA in retinal cells. In the INL, it is suggested that the major cells
      that express c-fos mRNA after focal retinal injury were the Muller cells. These
      results suggest that c-fos may be involved in the transcription in the Muller
      cells after injury to the retina.

PMID- 7822155
TI  - Polyclonal use of T-cell receptor alpha for human T-cell lymphotropic virus type
      1-infected T cells.
AB  - PURPOSE: To understand better the immunopathology of HTLV-I uveitis by
      investigating the clonality of HTLV-I-infected T-cell clones. METHODS: Eleven T
      cell clones were established from the aqueous humor (six clones) and the
      peripheral blood (five clones) of a patient with HTLV-I uveitis, and the
      clonality of the HTLV-I-infected T cells was investigated by sequencing the T
      cell receptor (TCR) alpha gene after the amplification of TCR alpha cDNA using an
      adaptor-ligation method and reverse transcriptase-polymerase chain reaction (RT
      PCR). RESULTS: TCR alpha use was different for each of 11 T-cell clones,
      encompassing eight different HTLV-I-infected T-cell clones (four from the aqueous
      humor and four from peripheral blood) and three HTLV-I-negative T-cell clones.
      CONCLUSIONS: This study demonstrated polyclonal use of TCR alpha for HTLV-I
      infected T cells in the ocular lesion and the peripheral blood. Results suggested
      that these T cells are not precursors of the leukemic cells associated with
      malignant transformation. Instead, they might be randomly infected with HTLV-I in
      the process of HTLV-I uveitis.

PMID- 7822157
TI  - Excimer laser corneal surgery: new strategies and old enemies.

PMID- 7822156
TI  - Expression of E6/E7 or SV40 large T antigen-coding oncogenes in human corneal
      endothelial cells indicates regulated high-proliferative capacity.
AB  - PURPOSE: Human corneal endothelial cells are thought to have limited capacity for
      proliferation. Little is known about the mechanisms that regulate the
      proliferation of these cells. The authors introduced oncogenes into human corneal
      endothelial cells to modulate proliferation. In addition, they sought to
      establish cell lines to facilitate study of human corneal endothelial cells.
      METHODS: Early-passage human corneal endothelial cells were transduced with
      disabled retrovirus (pLXSN16E6/E7) coding for the human papilloma virus type 16
      transforming oncoproteins E6 and E7. Early-passage cells were also stably
      transfected by electroporation with the pMTV-D305 plasmid vector, in which SV40
      large T antigen (SV40 LTAg) mRNA expression is positively regulated by the mouse
      mammary tumor virus promoter. Expression of E6/E7 mRNA or SV40 LTAg mRNA in cell
      lines was monitored with the polymerase chain reaction. SV40 LTAg protein
      expression was detected by immunocytology and Western blot analysis. RESULTS:
      Human corneal endothelial cells were efficiently infected with disabled
      retrovirus coding for E6/E7, and seven strains of cells have continued active
      proliferation for more than 50 population doublings (PD) (< 8 control PD). E6/E7
      mRNA was expressed by each cell strain. E6/E7 transformed cells proliferate
      rapidly and form a monolayer of cells with a high degree of contact inhibition.
      Transfection with pMTV-D305 is less efficient, and only a single strain was
      developed. pMTV-D305-transfected endothelial cells (dexamethasone induced)
      proliferated at a lower rate than E6/E7-transduced cells or cells transfected
      with a vector (pSV3neo) in which SV40 LTAg is constitutively regulated. In the
      absence of dexamethasone, the proliferation of pMTV-D305-transfected cells was
      even slower, but cells continued to produce SV40 LTAg mRNA and protein. The
      latter results indicated that SV40 LTAg mRNA continued to be synthesized at
      significant levels in pMTV-D305-transfected cells in the absence of the inducer
      dexamethasone. CONCLUSIONS: This study suggests that human corneal endothelial
      cells have a high capacity for proliferation. Thus, cell division is normally
      controlled in human corneal endothelial cells by poorly characterized, but
      efficient, mechanisms. Because the E6 and E7 proteins, as well as the SV40 large
      T antigen, specifically bind to and interfere with the activity of the
      retinoblastoma (RB) and p53 tumor suppressor proteins, our results suggest that
      these proteins have critical roles in regulating the proliferation of human
      corneal endothelial cells.

PMID- 7822158
TI  - Ocular inoculation of monkeys with simian varicella virus: clinical and
      histopathologic observations.
AB  - PURPOSE: To explore the possibility that inoculation of the eyes of African green
      monkeys with simian varicella virus (SVV) induces the symptoms of herpes zoster
      ophthalmicus (HZO), as seen in humans, and to develop a realistic and
      reproducible animal model of herpes zoster ophthalmicus for experimental studies.
      METHODS: In the first experiment, the right eyes of three African green monkeys
      were inoculated by intrastromal and subconjunctival injections with a suspension
      of SVV-infected Vero cells. In the second experiment, three additional monkeys
      were pretreated with intramuscular injections of methylprednisolone (41 mg/kg)
      for 7 days before ocular inoculation with SVV and for 3 weeks at 14 mg/kg after
      virus inoculation. The eyes were examined by slit-lamp biomicroscopy. Histologic,
      immunohistochemical, and electron microscopic studies were performed. RESULTS: In
      the first experiment, all three animals developed high titers of anti-SVV
      antibodies (IgG). Diffuse stromal opacity, with keratitic precipitates, stromal
      edema, and mild vascularization of the cornea, appeared 12 to 14 days after
      inoculation. The onset of ocular disease was correlated with the rise in serum
      antibody levels. There was no clinical evidence of a systemic viral infection
      resulting from the corneal inoculations in these monkeys. In the second
      experiment, all three animals treated with methylprednisolone developed severe
      ocular pathology within 1 week of inoculation. The clinical appearance of the
      diseased eyes strongly indicated that local viral infection had occurred.
      Dendritiform keratitis, corneal erosion, and stromal necrosis with
      vascularization of the cornea was seen in all the eyes. The disease resolved
      within 4 to 5 weeks of inoculation, leaving opaque, vascularized corneas.
      Histologic studies showed that inflammatory cells and viral antigens were
      widespread throughout the diseased corneas. A high titer of anti-SVV antibody
      (IgG) was detected in the immunosuppressed monkeys, but no evidence of systemic
      viral infection was observed. CONCLUSIONS: The authors propose that inoculation
      of the eyes of methylprednisolone-treated African green monkeys with simian
      varicella virus provides an appropriate animal model for studies of the virology
      and immunopathology of ocular varicella virus infection.

PMID- 7822159
TI  - Effect of topically applied anti-CD4 monoclonal antibodies on orthotopic corneal
      allografts in a rat model.
AB  - PURPOSE: Monoclonal antibodies (mAb) have generated interest as therapeutic
      agents. Limited data are available on the treatment of corneal graft rejection.
      The purpose of this study was to assess the use of topically applied mAb on
      experimental corneal grafts. METHODS: W 3/25, an IgG 1 mouse antirat mAb that
      recognizes a CD4+ cell subset, was used to treat Lewis recipient rats that
      received orthotopic corneal grafts of Wistar-Furth donors. Recipients were
      randomly assigned to receive topically applied drops of liposome-incorporated
      anti-CD4 mAb (LIP-anti-CD4 mAb), an equivalent amount of free anti-CD4 mAb, an
      isotype-matched control mAb encapsulated in liposomes (LIP-control mAb), or empty
      liposomes (emp-LIP) 5 times daily for 10 days. To investigate the immunologic
      effect of mAb treatment, flow cytometry of the targeted cells and cytotoxic
      activity of lymphocytes were analyzed. RESULTS: Application of LIP-anti-CD4 mAb
      was effective in reducing the rejection rate (P < .05) and in prolonging the mean
      survival time of corneal grafts that underwent rejection (P < .05). In contrast,
      no significant effect on graft outcome was observed after the application of
      control agents. Flow cytometry analysis did not reveal systemic depletion of the
      targeted lymphocyte subset in any anti-CD4 mAb treated animals. Rejected grafts
      elicited a cellular cytotoxic immune response in a cell-mediated lymphocytotoxic
      assay independent of the treatment given. CONCLUSION: The results suggest that
      treatment with topically applied LIP-anti-CD4 mAb prolongs graft survival in
      orthotopic corneal grafts in a rat model. The beneficial effect of LIP-anti-CD4
      mAb, probably due to enhanced intraocular delivery, was achieved by using
      relatively low doses of mAb.

PMID- 7822160
TI  - Functional abnormalities in transgenic mice expressing a mutant rhodopsin gene.
AB  - PURPOSE: To evaluate the consequences of the expression of a mutant mouse opsin
      gene on rod- and cone-mediated function. Experimental conditions were chosen to
      provide a basis of comparison to the results reported for patients with autosomal
      dominant retinitis pigmentosa (ADRP) in whom the proline at position 23 has been
      replaced by a histidine (P23H). METHODS: The mutated gene product resulted in
      three substitutions in the rhodopsin molecule: P23H, glycine for valine at
      position 20 (V20G), and leucine for proline at position 27 (P27L). Mice positive
      for the transgene were differentiated from normal littermates by the polymerase
      chain reaction. Electroretinograms (ERGs) were obtained from anesthetized mice
      between 1 and 9 months of age. After photically bleaching approximately 18% of
      the available rhodopsin, the time course of rod dark adaptation was examined by
      monitoring rod ERG amplitude recovery. Rhodopsin densitometry was used to
      determine the relative amounts of rhodopsin in the retinae of normal and
      transgenic mice. RESULTS: ERGs obtained from transgenic mice showed a significant
      reduction in rod-mediated response amplitude at 1 month of age and a relatively
      slow progressive decrease thereafter. Cone-mediated ERGs, on the other hand, were
      nearly normal in amplitude for approximately the first 5 months after birth, but
      at later ages response amplitudes also underwent a progressive decline. In the
      normal retina, rod ERG amplitudes returned to prebleach levels within 30 minutes,
      whereas in transgenic mice response amplitudes did not recover within a 2-hour
      test period. The age-related decline in rod-mediated electroretinal potentials
      seen in transgenic mice was paralleled by a concomitant fall in rhodopsin
      density, and the sensitivity losses obtained electroretinographically could be
      accounted for solely on the basis of reduced quantal absorption. CONCLUSIONS: The
      pattern of functional changes seen in the transgenic mice are in good agreement
      with those reported in patients with ADRP with the P23H mutation in the rhodopsin
      gene. Particularly noteworthy is the fact that the changes in rhodopsin density
      and visual sensitivity are associated with a progressive shortening of the rod
      outer segments; the histologic changes induced by the disease process in patients
      with ADRP have yet to be determined.

PMID- 7822161
TI  - Cloning and characterization of rod opsin cDNA from the Old World monkey, Macaca
      fascicularis.
AB  - PURPOSE: Opsin sequences from different phyla have been compared to examine the
      structural and functional regions of this molecule and to assess the molecular
      evolution of genes in the animal kingdom. Of all the sequences reported, there is
      only one primate sequence (human) for rod opsin. To extend our knowledge of the
      primate family of opsins, the authors cloned and characterized the opsin cDNA for
      the Old World monkey Macaca fascicularis and determined its position in the
      phylogenetic tree of the opsin gene family. METHODS: A fragment of the monkey
      opsin cDNA was generated using specific primers and the polymerase chain
      reaction. This fragment was then used as a probe to isolate several cDNA clones
      from a M. fascicularis retinal cDNA library. The nucleotide sequence of monkey
      opsin was determined and translated into an amino acid sequence. The amino acid
      sequences of opsins from a variety of organisms ranging from mollusks,
      arthropods, and vertebrates, including monkey, were then compared to identify
      highly conserved amino acid residues and to construct a phylogenetic tree of the
      rod opsins. RESULTS: The monkey has a single major 2.2-kb transcript for opsin
      and minor transcripts of 1.5, 4.8, and 8.9 kb. The major transcript is highly
      abundant in the monkey retina and is localized to the inner segments of rod
      photoreceptor cells, typical of opsin mRNAs in other organisms. The sequence of
      monkey opsin closely resembles the human sequence at the nucleotide and the amino
      acid levels, with the latter having only 7 differences out of 348 residues.
      Comparison of the monkey sequence with the amino acid sequences from diverse
      organisms shows that all opsins share only 34 conserved amino acids, with the
      highest concentration of these residues occurring in the first cytoplasmic loop
      of rhodopsin. A hypothetical phylogenetic tree of the opsins suggests that both
      human and monkey opsin shared an ancestral gene with the mammalian Order
      Carnivora. CONCLUSION: The opsins of man and Old World monkeys have diverged
      little from the time they shared a common ancestor. Comparison of opsins from
      diverse phyla, however, shows that only 34 residues have been conserved. These
      conserved residues are likely to be important in the structure and function of
      rhodopsin.

PMID- 7822162
TI  - Na,K-ATPase response to osmotic stress in primary dog lens epithelial cells.
AB  - PURPOSE: Na,K-ATPase activity increases in lens cells exposed to hypertonic
      stress. To test whether the increase in activity involves stimulation of Na,K
      ATPase expression, dog lens epithelial cells were subjected to hypertonic stress,
      and the time course of Na,K-ATPase protein and mRNA response was measured.
      METHODS: Primary cultures of dog lens epithelial cells were maintained in
      isotonic or hypertonic media over the course of several days. Rubidium-86 uptake
      measurements, immunoreactive protein, and northern blot analysis were performed.
      RESULTS: Dog lens epithelial cells exposed to hypertonic stress from culture
      medium supplemented with 150 mM NaCl or 250 mM cellobiose showed a twofold
      increase in Na,K-ATPase activity. The increase in activity was blocked by
      cycloheximide and was reversible when the cells were returned to isotonic medium.
      This activity was unaffected by the aldose reductase inhibitor, tolrestat. Na,K
      ATPase protein and mRNA levels increased in cells exposed to medium containing
      150 mM NaCl. Northern blot analysis showed that the alpha-1 and beta-1 mRNA
      levels increased as early as 6 hours and maximally increased 1.5-fold to twofold
      by 12 to 24 hours. CONCLUSIONS: Elevation of Na,K-ATPase activity in dog lens
      epithelial cells exposed to hypertonic stress was associated with increased
      expression of Na,K-ATPase subunit mRNAs and was dependent on protein synthesis.
      These results suggest that upregulation of the enzyme activity is the result of
      an induction of Na,K-ATPase.

PMID- 7822163
TI  - Evaluation of therapeutic measures for treating endophthalmitis caused by
      isogenic toxin-producing and toxin-nonproducing Enterococcus faecalis strains.
AB  - PURPOSE: Management of endophthalmitis typically includes antibiotic combinations
      to arrest bacterial growth and antiinflammatory agents to limit inflammatory
      damage to sensitive tissues. Little research has been reported that
      systematically evaluates the contribution of each therapeutic component for
      treating infections caused by organisms of varying virulence. The authors
      determined the relative value of the antinflammatory corticosteroid,
      dexamethasone, as an intravitreal therapeutic adjunct for the treatment of
      infection caused by either Enterococcus faecalis expressing a cytolytic toxin
      previously shown to contribute to the course and severity of infection, or an
      otherwise identical strain of E. faecalis specifically attenuated in expression
      of the cytolytic toxin. METHODS: Endophthalmitis in rabbits was monitored using
      electroretinography (ERG). Eyes were infected with 100 colony forming units of
      either the cytolytic or the noncytolytic E. faecalis strain. Intravitreal
      ampicillin and gentamicin were administered at postinfection day 1, and
      intravitreal dexamethasone was either omitted or administered at day -1, 1, or
      1.5. RESULTS: ERG B-wave amplitude declined precipitously throughout the course
      of infection with cytolytic toxin-producing E. faecalis, despite the
      administration of antibiotics and regardless of the time of dexamethasone
      administration. In fact, the ultimate course of infection caused by cytolytic E.
      faecalis did not differ from the course in untreated controls. In contrast,
      infections caused by specifically attenuated, noncytolytic strains of E. faecalis
      responded well to antibiotics augmented by antiinflammatory therapy when the
      latter was administered either 1 or 1.5 days after the initiation of infection.
      In these cases, no loss in ERG B-wave response was observed. CONCLUSIONS: These
      results underscore the importance of bacterial toxins in infectious diseases of
      the eye and their contribution to treatment failures. These results further
      suggest that in cases of endophthalmitis caused by toxin producing bacteria,
      significant improvement in clinical outcome will require specific therapeutic
      targeting of the toxins involved.

PMID- 7822164
TI  - Pertussis toxin-sensitive melatonin receptors negatively coupled to adenylate
      cyclase associated with cultured human and rat retinal pigment epithelial cells.
AB  - PURPOSE: Studies were conducted to investigate the influence of melatonin on
      adenylate cyclase activity in cultured human and rat retinal pigment epithelial
      (RPE) cells. METHODS: Adenylate cyclase activity was assessed by measurement of
      cAMP levels in cultured RPE cells using a specific cAMP-binding protein isolated
      from bovine adrenal cortex to detect cellular cAMP by competition with a standard
      amount of tritiated cAMP. The effects of melatonin on basal cAMP levels and those
      induced by the direct activator of adenylate cyclase, forskolin, were studied.
      RESULTS: Exposure of human RPE cells to 100 microM of melatonin had no effect on
      basal cAMP levels, but it caused a 41% reduction in the forskolin (5 microM)
      stimulation of cAMP. This melatonin-induced reduction in forskolin-stimulated
      adenylate cyclase activity was dose dependent, with half-maximal (EC50) reduction
      at 4.2 x 10(-10) M. 2-iodomelatonin, 6-chloromelatonin, and 6-hydroxymelatonin
      mimicked the melatonin effect with EC50 values of 3.5 x 10(-10) M, 4.3 x 10(-9)M,
      and 1.9 x 10(-7)M, respectively. Preexposure of cells to pertussis toxin (100
      ng/ml) for 18 hours completely attenuated the ability of melatonin to influence
      the forskolin stimulation of cAMP levels. Propranolol did not influence the
      action of melatonin but did antagonize the ability of serotonin to reduce the
      forskolin-elevated cAMP levels. Thus, melatonin receptors are distinct from
      serotonin receptors. Melatonin receptors negatively linked to cAMP metabolism are
      also associated with cultured hooded rat RPE cells. Melatonin and iodomelatonin
      caused dose-dependent reductions in forskolin-stimulated cAMP production with
      half-maximal values of 2.4 x 10(-9)M and 3.28 x 10(-9)M, respectively.
      CONCLUSIONS: The results show that human and rat RPE cells possess melatonin
      receptors negatively coupled to adenylate cyclase and sensitive to pertussis
      toxin.

PMID- 7822165
TI  - Health system reform is very much alive.

PMID- 7822166
TI  - Post-mortem on health system reform.

PMID- 7822167
TI  - Correct coding for Medicaid EPSDT.

PMID- 7822169
TI  - Finding the best consultant.

PMID- 7822168
TI  - Iowa's Workers' Compensation System.

PMID- 7822170
TI  - How capitation works.

PMID- 7822171
TI  - Primary malignant melanoma of the lower lip.
AB  - Melanomas in the anatomically complex area of the head and neck impose formidable
      obstacles to treatment. Mucosal melanomas, for reasons which remain uncertain,
      are associated with a poorer prognosis. Because no systemic treatment is known to
      be effective, increased awareness by patients and a high index of suspicion is
      warranted. The disease is potentially curable if diagnosed and treated at an
      early stage.

PMID- 7822172
TI  - An Osler year.

PMID- 7822173
TI  - Moratorium on multi-institutional head and neck cancer trials.

PMID- 7822174
TI  - A call for participation in intergroup trials.

PMID- 7822175
TI  - Follicular carcinoma of the thyroid.
AB  - BACKGROUND: Follicular carcinomas of the thyroid are less common than papillary
      carcinomas of the thyroid, and the available data on prognostic factors are
      relatively scant. A retrospective study covering four decades was undertaken to
      evaluate clinical and pathologic findings with regard to their effect on
      prognosis. METHODS: In 195 cases of follicular carcinoma treated from 1954 to
      1991 age, sex, histologic type (minimally invasive vs. widely invasive), tumor
      size, and local, regional, and distant spread as well as the contribution of
      treatment to survival were evaluated in relation to prognosis. RESULTS: Age was a
      significant prognostic factor: there was 100% survival of patients younger than
      20 years of age at diagnosis and only one death in the 20-39 year age group. Sex
      was not a significant prognostic factor, although there was a tendency to a
      better prognosis in females. Tumor size was significant, more than 6 cm having a
      poor prognosis. Blood vessel invasion influenced prognosis for the first 10
      years. The presence of distant metastases was significant regarding survival.
      Lymph node involvement had a negative effect on the outcome. CONCLUSIONS: The
      factors of age, tumor size, invasion of blood vessels, and distant metastases are
      significant predictors of survival for patients with follicular carcinoma,
      whereas sex is not; regional spread needs to be evaluated further.

PMID- 7822176
TI  - Precancerous lesions of the larynx: clinical and pathologic correlations and
      prognostic aspects.
AB  - BACKGROUND: Medical literature on the development of malignancy shows wide
      ranging limitations depending on the criteria considered, but all authors agree
      that the presence of dysplasia in the sample is an important prognostic sign.
      METHOD: This is a retrospective study of 248 patients controlled and treated at
      the ENT and Pathology Departments of the Hospital Clinic in Barcelona between
      1981 and 1991 for larynx lesions. Biopsy studies of the following pathologic
      entities were carried out: keratosis, chronic inflammation, and papilloma of the
      adult. The degree of dysplasia present in each sample was assessed. RESULTS: The
      overall percentage of malignancy was 15.6% in this series. Malignancy developed
      in 8.7% of the cases without dysplasia and in 31% (p < 0.0001) with dysplasia.
      The groups were correlated with gender, age, and smoking habit. The presence of
      epithelial dysplasia is an important prognostic factor. The risk of malignant
      transformation increases if the dysplasia occurs in smokers.

PMID- 7822177
TI  - Tongue flaps for reconstruction of the oral cavity.
AB  - Pedicled tongue flaps (anterior, posterior, double) have proved to be an
      effective method of repairing defects due to tissue loss in the oral cavity.
      Their central position, mobility, and excellent blood supply make the use of
      these flaps feasible in a variety of sites.

PMID- 7822178
TI  - Recurrence of laryngeal or hypopharyngeal primary tumor after radical neck
      dissection for postradiotherapy neck nodal metastases.
AB  - BACKGROUND: When the primary tumor in the larynx or hypopharynx responds well to
      radiotherapy, nodal metastasis in the neck may persist or recur. The primary site
      is usually left alone when no lesion is evident, but its long-term control is
      uncertain. METHODS: Radical neck dissection was performed in 23 patients who had
      nodal metastasis, while the primary tumor in the larynx or hypopharynx was
      controlled after radiotherapy. The primary site was left alone and kept under
      surveillance. RESULTS: Seven patients (30%) had recurrence at the primary site on
      follow-up. Two significant risk factors for development of recurrences at the
      primary site were identified; the neck node staging at presentation (p < 0.03)
      and presentation with persistent neck lymph nodes (p < 0.03). The 2-year survival
      of those patients with recurrences at the primary site was 29%. CONCLUSION:
      Radical neck dissection alone was justified, but close surveillance of the
      primary site after surgery is mandatory, especially for those patients with high
      risk factors.

PMID- 7822179
TI  - Functional status and coping in patients with oral and pharyngeal cancer before
      and after surgery.
AB  - BACKGROUND: Few studies, prospective or retrospective, exist that describe the
      quality of life of patients with oral or pharyngeal cancer. This study describes
      functional status, measured by the sickness impact profile (SIP), and coping,
      measured by the sense of coherence (SOC) scale, in a group of patients treated by
      surgery for oral or pharyngeal cancer. METHODS: Forty-two patients, divided into
      two groups, participated in the study. Twenty-seven patients completed SIP and
      SOC scale 12 months after treatment (the 12-month follow-up group), and 15
      patients completed SIP and SOC scale before surgery and SIP 2-4 months and 12
      months after treatment (the prospective group). The patients were also classified
      according to the extensiveness of their surgery: minor, moderate, or major.
      RESULTS: The psychosocial and physical functioning as well as the functions of
      recreation/pastimes, sleep/rest, home management, work, and eating were rated as
      being impaired 2-4 months and also 12 months after treatment. However, the
      obtained values were spread over a wide range, with large individual differences.
      Functional limitations were related to more extensive surgery and also to less
      successful coping. CONCLUSION: This study reveals the need of individualized
      rehabilitation for these patients, and that the SIP and the SOC scale may serve
      as evaluation tools in a rehabilitation program.

PMID- 7822180
TI  - Assessment of cryoprecipitate-thrombin solution for dural repair.
AB  - BACKGROUND: After resection of cranial and skull base tumors, fibrin-thrombin
      solutions can provide a temporary biologic seal of dural closures until final
      healing occurs. We investigated several variables affecting the strength of these
      "tissues glues" for repair of dural defects using in vitro methods to model
      clinical repairs. METHODS: The competence of human cryoprecipitate-thrombin (CPT)
      "tissue glues" in providing a watertight seal for patched rat fascia and human
      cadaveric dural defects was assessed. A saline column was fabricated to allow for
      controlled pressure (up to 700 mm) to be applied over an open aperature
      containing the repaired defect. Variables of repair included time after repair,
      defect size, and mixing temperature. RESULTS: Wide variations in the strength of
      different cryoprecipitate glues were found. Time allowed after repair did not
      significantly affect the repair strength. Cooling the components of the glue
      solution prior to mixing significantly increased repair strength. Similar results
      were found for different defect sizes. CONCLUSIONS: Under controlled in vitro
      conditions, integrity of fibrin glue repairs varied widely. This was not
      attributable to differences in solution fibrinogen concentration. Cooling the
      "tissue glue" components prior to mixing significantly increased repair strength
      of patched tissue defects.

PMID- 7822182
TI  - Skull base chondroma of extracranial origin.
AB  - METHODS: Two cases of chondroma at the skull base, most probably of extracranial
      origin, are presented: one at the apex of the petrous pyramid and the other in
      the infratemporal fossa. RESULTS: In the second case, the surgical findings
      suggested that the tumor originated in the cartilagineous part of the eustachian
      tube. The world literature was reviewed and only three cases of extracranial
      chondromas at the skull base, and ten cases of chondromas of the nasopharynx have
      been described so far. CONCLUSIONS: The potential origins of chondromas at the
      skull base are discussed: Cartilagineous remnants at the basisphenoid and
      basiocciput or the cartilagineous part of the eustachian tube seem to be the most
      probable origin.

PMID- 7822181
TI  - Craniofacial resection at the University of Virginia (1976-1992): survival
      analysis.
AB  - BACKGROUND: The purpose of this study is to evaluate the survival of patients
      treated at the University of Virginia Health Sciences Center with an anterior
      craniofacial resection in conjunction with radiotherapy and/or chemotherapy for
      malignancies of the superior sinonasal cavity. In addition, the impact of
      aggressive salvage therapy for patients with recurrent disease is considered.
      METHODS: Between June 1976 and December 1992, a total of 45 patients underwent a
      craniofacial resection by the Departments of Otolaryngology-Head and Neck Surgery
      and Neurological Surgery at the University of Virginia. One patient was excluded
      from the analysis because his neoplasm was benign. Another patient died 2 days
      postoperatively from multiple strokes. The remaining 43 patients were divided
      into two subgroups: (1) patients with esthesioneuroblastoma (24 patients) and
      patients with non-esthesioneuroblastoma malignancies (19). Their survival curves
      were estimated for the percent survival free of disease by month of follow-up
      using the product limit of Kaplan and Meier. In addition, the salvage treatment
      for recurrences was examined for both groups. RESULTS: The 5-year disease-free
      survival rate for the entire group was 77%, with a 2.3% postoperative mortality.
      The 5-year disease-free survival for the esthesioneuroblastoma patients was 90%,
      and that for the non-esthesioneuroblastoma group was 59.1% (p = 0.028). Four of 8
      esthesioneuroblastoma patients who recurred and were treated with aggressive
      salvage therapy were without evidence of disease 5 years after completion of
      therapy, and 3 of the 10 non-esthesioneuroblastoma patients salvaged were without
      evidence of disease 57.3 months after therapy (39% surgical salvage).
      CONCLUSIONS: There is a statistically significant difference between the 5-year
      disease-free survival for the esthesioneuroblastoma patients and the non
      esthesioneuroblastoma patients (90% vs 59.1%; p = 0.028), and aggressive salvage
      therapy appears to be a more successful option in the esthesioneuroblastoma group
      of patients.

PMID- 7822183
TI  - Squamous cell carcinoma arising in Hashimoto's thyroiditis.
AB  - The case of a 76-year-old white woman with squamous cell carcinoma of the thyroid
      gland arising in a background of Hashimoto's thyroiditis is presented. Squamous
      cell carcinoma of the thyroid gland is a very rare and aggressive tumor, and only
      a few cases are reported as arising in Hashimoto's thyroiditis. Although
      Hashimoto's thyroiditis alone does not necessarily predispose patients to
      malignancy, the finding of a prominent nodule in such a patient should suggest
      the possibility of malignancy, and an aggressive search and treatment regimen,
      including surgical intervention, should be pursued.

PMID- 7822184
TI  - Large thyroglossal duct cyst with laryngeal extension.
AB  - BACKGROUND: A thyroglossal duct cyst typically presents as a long-standing neck
      mass that becomes symptomatic when inflamed. Hoarseness is an uncommon complaint,
      and its association may suggest encroachment on and destruction of the larynx.
      Following removal of the cyst with the Sistrunk procedure, the larynx may need to
      be reconstructed. METHODS: A case is reported of a patient who was initially seen
      with hoarseness and a long-standing midline neck mass. Computed tomography (CT)
      demonstrated a large cystic neck mass that eroded the thyroid cartilage and
      encroached on the pre-epiglottic space and right paraglottic space. Although the
      clinical impression was that of laryngeal neoplasm, the CT diagnosis was that of
      a cyst. At surgery, a thyroglossal duct cyst was found and successfully removed
      with the Sistrunk procedure. Because the thyrohyoid membrane and thyroid
      perichondrium were preserved, the glottis did not require reconstruction. This
      case is presented and the literature of thyroglossal duct cysts that extend into
      the larynx is reviewed. CONCLUSIONS: The clinical and radiographic criteria that
      suggest encroachment of a thyroglossal duct cyst on the larynx are reviewed. The
      management and indications for laryngeal reconstruction are discussed.

PMID- 7822185
TI  - Undifferentiated nasopharyngeal carcinoma presenting as a parotid mass.
AB  - BACKGROUND: Nasopharyngeal carcinoma has a variety of presentations. However, in
      more than 50% of cases it may present with serous otitis or cervical metastases.
      Although the metastases usually occur in the neck, the lymphatic network of the
      parotid may also serve as a site for the metastatic deposits. We present a case
      in which the initial manifestation of nasopharyngeal carcinoma of the
      lymphoepithelioma type was a parotid mass. METHODS: Case study. RESULTS: A
      patient who was initially seen with an isolated parotid mass was found to have an
      undifferentiated carcinoma of the lymphoepithelial type. Further evaluation
      identified an occult nasopharyngeal carcinoma, and the patient underwent
      radiotherapy. CONCLUSIONS: A diagnosis of a malignant lymphoepithelial lesion of
      the parotid gland or undifferentiated carcinoma of the lymphoepithelial type
      mandates a search for an occult primary nasopharyngeal tumor.

PMID- 7822186
TI  - Aneurysmal bone cyst of the zygomatic arch.
AB  - BACKGROUND: Aneurysmal bone cysts are rare vascular lesions that are most
      commonly found in the long bones. They are rare in the head and neck. Only two
      prior cases of aneurysmal bone cysts of the zygoma have been reported in the
      world literature. RESULTS: We report a case of aneurysmal bone cyst arising in
      the zygomatic arch with intracranial extension treated with selective arterial
      embolization and complete excision via an intratemporal fossa approach. This is
      the first such case reported in the head and neck surgery literature.
      CONCLUSIONS: Selected cases of aneurysmal bone cyst may be safely treated with
      selective arterial embolization and complete resection.

PMID- 7822187
TI  - Bilateral parotid neoplasms.
AB  - In this case, the experts come out of the starting blocks disagreeing. One expert
      (Dr. Myers) does not routinely use FNA, relying instead on clinical signs to
      suspect a malignancy. the other physicians (Drs. Robbins and Suen) obtain an FNA
      for each parotid mass and use the information in counseling patients. MRI is an
      important preoperative tool for one physician (Dr. Suen). When faced with
      bilateral tumors, one approach is to stage the operations to avoid possible
      bilateral facial nerve injury (Dr. Myers). Other approaches include operating on
      the larger tumor first if both are benign, the malignant tumor first if one is
      benign and one malignant, and on both sides under the same anesthetic if both are
      malignant (Dr. Robbins). The other consultant agrees with this latter approach,
      with the exception being that in the case of bilateral benign tumors, he would
      operate on the smaller side first (Dr. Suen). Regarding the role for further
      surgery, one expert would reoperate if there were a suspicion for residual gross
      tumor on the facial nerve (Dr. Robbins). The others (Drs. Myers and Suen) agree
      that the positive margin likely reflects microscopic disease and further surgery
      is not warranted. Radiotherapy is recommended by all the experts. There is no
      proven role for chemotherapy. There is disagreement regarding whether the facial
      nerve should have been removed on the left side. Two experts (Drs. Myers and
      Suen) agree on peeling tumor off the nerve and following with radiotherapy.
      However, one physician (Dr. Robbins) believes that the facial nerve should have
      been removed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7822188
TI  - Diagnosing strategic performance of the hospital information systems planning
      cycle.
AB  - Hospital information systems planning (HISP) involves large expenditures. Often
      the evaluation of its performance is unstructured, giving no direction for future
      strategic choices for information systems (IS) development. This article
      formulates the challenge facing senior management when it must define priorities
      for the next IS planning cycle. New IS applications are selected to enhance the
      IS portfolio profile and the users' functionality, taking account of the past and
      anticipated response to resources invested. A methodology, new tools, and
      analyses for conducting the diagnosis of the last planning cycle are described.

PMID- 7822189
TI  - The contribution of hospitals to a local economy: a case study in Iowa and
      Illinois.
AB  - This study assessed the importance of the hospital sector to a regional economy
      by examining the estimated effects of direct and indirect hospital spending on
      the income and employment of a metropolitan region in Iowa and Illinois. The
      evaluation included the role of hospital services as a regional "export." In
      addition, the stabilizing impact of hospital spending during business cycles was
      examined. Results of the study indicated that the hospitals played a vital role
      in the economic stability and growth of the local community.

PMID- 7822190
TI  - Hospital bankruptcies: an exploration of potential causes and consequences.
AB  - Although small in number, hospitals are increasingly seeking bankruptcy
      protection. This article explores the potential forces that might motivate
      hospitals to seek bankruptcy protection and the potential consequences for
      hospitals that obtain it. Case reviews of 11 hospital bankruptcies that occurred
      in 1990 and 1991 are presented. The findings should assist hospital executives,
      trustees, financial analysts, and legal counsel as they assess bankruptcy as an
      option for distressed hospitals.

PMID- 7822191
TI  - Determining costs associated with quality in health care delivery.
AB  - This article examines the costs associated with quality in health care delivery.
      A model applicable to health care settings is specified according to investments
      in quality and the cost of not achieving quality. The premises and basic theories
      underlying the model are explored. The model was developed at Lovelace Health
      Systems in Albuquerque, New Mexico, as a decision making tool. The specific cost
      elements comprising the quality cost model are identified and illustrated using
      the working model adopted at Lovelace. The managerial impact of the quality cost
      model and the implications for other health care organizations are examined.

PMID- 7822192
TI  - Determinants of union victory in the health care sector.
AB  - Union win rates in the health care sector (October 1988 to September 1992) were
      significantly higher in multiple union elections, small bargaining units, and non
      AFL-CIO single union elections. The 1991 Supreme Court Decision (AHA v. NLRB)
      negatively affected union win rates in hospitals.

PMID- 7822193
TI  - Implementing organized delivery systems: an integration scorecard.
AB  - Organized vertically integrated health systems are in a key position to play a
      major role in present health care reform efforts. To demonstrate a competitive
      advantage in the new health care environment, however, integration efforts must
      be successful. Based on a national study of nine organized delivery systems, this
      article develops measures of three types of integration that occur in vertically
      integrated health systems--functional, physician-system, and clinical. These
      measures can be used as a "scorecard" to assess progress toward achieving
      integration objectives.

PMID- 7822194
TI  - The looming fight over health care reform: what we can learn from past debates.
AB  - There have been numerous debates over reforming our health care system. A careful
      examination of the outcome of these debates may indicate what lies ahead for you
      when you make your next doctor's appointment.

PMID- 7822195
TI  - HCMR dialogue: the Johnson-Brown debate continues.

PMID- 7822196
TI  - [The tumor suppressor gene p53 and its significance for dermatology].
AB  - The product of the p53 tumour suppressor gene is a sequence-specific DNA-binding
      protein that acts as a transcription factor and can inhibit transformation in
      vitro. Mutational inactivation of p53 is the most frequent genetic alteration
      found in human cancer. Point mutations of the p53 gene have been detected in
      about 50% of squamous cell carcinomas, basaliomas and cases of Bowen's disease. A
      significant portion of these mutations were CC-->TT or C-->T transitions
      suggestive of UV involvement in mutagenesis. Increased concentrations of p53
      protein were immunohistochemically detected in cutaneous malignant melanomas, but
      p53 mutations are rare in this tumour.

PMID- 7822197
TI  - [Extracorporeal photopheresis].
AB  - Extracorporeal photopheresis is a new therapeutic approach developed by Edelson
      et al.; it is conceptually designed for the management of diseases mediated by
      malignant lymphocyte pathology, such as cutaneous T-cell-lymphoma (CTCL), and
      other disorders mediated by aberrant lymphocyte function, e.g. autoimmune
      diseases. The treatment is described in this paper, and theories on the
      mechanisms of action are discussed. In addition, the indications for treatment
      with extracorporeal photopheresis are discussed.

PMID- 7822198
TI  - [Group sports as adjuvant therapy for patients with atopic eczema].
AB  - The therapeutic value of regular physical exercise for patients with atopic
      eczema (AE) and other chronic inflammatory dermatoses has not yet been
      investigated systematically. At our institution an adjuvant group sports
      programme for voluntary inpatients has been in place for 3 years. Using a
      standardized questionnaire we found positive psychological influences of this
      program on the patients' mood and psychosocial wellbeing. Since most
      dermatologists, however, regard sweating as detrimental for patients with AE, we
      studied the impact of regular sports activities on the skin condition of AE
      patients otherwise subdued to usual dermatotherapy (yet without corticosteroids)
      by aid of a standardized symptomscore system. Thirty inpatients with AE
      participated regularly in the sports programme, another 30 inpatients with AE
      (the control group) did not. The skin condition improved similarly the two groups
      over the study period of about 3 weeks. Cutaneous thermoregulation (with one arm
      in a 41 degrees C water bath as thermic stimulus) was examined in patients with
      AE before and after the study period. While many AE patients initially showed
      paradoxical, i.e. decreasing, skin temperature in the contralateral arm, after 3
      weeks of physical training most of the participants had normalized consensual,
      i.e. increased, temperature reaction to the same warmth exposure. The conclusion
      is drawn that regular sports may be of adjuvant therapeutic value in patients
      suffering from AE, except in the acute stages of the disease.

PMID- 7822199
TI  - [Modification and optimization of tap water iontophoresis].
AB  - Tap water iontophoresis is the therapy of choice in hyperhidrosis palmoplantaris.
      Therapeutic regimens, however, vary greatly. The aim of the present study was to
      develop an optimized therapeutic scheme. The main methodologic parameters
      subjected to systematic experimental study included the effects of current
      polarity, the duration of a single treatment session, the addition of
      electrolytes to the tap water and the treatment interval during maintenance
      therapy. The following procedure is proposed. During the initial phase,
      treatments are carried out three times weekly for 10 min each time. The anode is
      kept on one extremity until normhidrosis is reached on this extremity. Then,
      polarity is changed until sweating is reduced to normal on the other extremity
      (constant polarity). In the subsequent maintenance phase, patients are treated at
      intervals of 6-8 days for 10 min each time. Polarity is switched from treatment
      to treatment (alternating polarity). Plain tap water is used without additives.

PMID- 7822200
TI  - [Value of nucleolus organizer regions (AgNORs) in dermatologic oncology].
AB  - Nucleolus-organizing regions (Ag-NORs) are silver-stained loops of DNA
      transcribing to ribosomal RNA. Quantitative analysis helps to differentiate
      normal tissue from malignant tissue and can be used for diagnosis in several
      kinds of tumours. The analysis of AgNORs can also be used in dermatopathology for
      diagnostic and prognostic purposes. Apart from skin tumours such as basal, cell
      carcinomas and squamous cell carcinomas, this technique is of interest
      principally for melanocytic lesions. Benign naevi can be distinguished from
      malignant melanomas by simple counting of the AgNOR dots. For the differentiation
      of dysplastic naevi, Spitz naevi and malignant melanomas, this parameter alone is
      not sufficient. By combination of several AgNOR parameters (number, size, pattern
      of dispersal) only, significant differentiation could be achieved. The prognostic
      value of AgNORs remains to be examined.

PMID- 7822201
TI  - [Pregnancy after drug therapy of severe andrological disorder].
AB  - Initial examination of an andrological patient revealed high-grade
      oligoasthenoteratozoospermia and ureaplasma infection. An elevated FSH level and
      significantly reduced testicular size were indicative of severely damaged
      testicular parenchyma. The presence of macrophages in the sperm smear was
      interpreted as a sign of chronic epididymitis. Antibiotic couple therapy with
      doxycycline, followed by a 3-month recovery period with combined treatment with
      vitamin C and E and zinc, resulted in a significantly improved spermiogram. After
      another 2 months intrauterine insemination resulted in pregnancy, and the birth
      of a healthy daughter followed. Preparation of the ejaculate was done by
      glasswool filtration. At that time, the patient had only mild teratozoospermia.

PMID- 7822202
TI  - [Chronic sclerodermiform graft versus host disease (GvHD)].
AB  - We report on a 41-year-old patient who developed extensive chronic
      sclerodermatous graft-versus-host disease (GvHD) subsequent to an allogeneic bone
      marrow transplantation from his HLA-identical sister. Chronic GvHD is to be
      expected in 30% of bone marrow transplantations. It is a serious multisystem
      disorder which leads to a polymorphic clinical picture with lichenoid or
      sclerodermatous skin changes. It may also affect nails, hair and mucous
      membranes. In the absence of causal therapy GvHD should be managed with
      symptomatic local treatment and systemic immunosuppression.

PMID- 7822203
TI  - [Erythrokeratolysis hiemalis. Erythematosquamous genetic dermatosis with seasonal
      manifestation].
AB  - Erythrokeratolysis hiemalis, keratolytic winter erythema or Oudtshoorn skin has
      been reported from the South African district of Oudtshoorn as a dominantly
      inherited dermatosis beginning in early childhood, in some cases with circinar
      scaling erythemas. Seasonal manifestation in winter-time and a characteristic
      multi-form histology distinguish this dermatosis from other childhood scaling
      erythemas. We present clinical, histological and preliminary immunohistological
      data of a 4-year-old girl with the attributes of erythrokeratolysis hiemalis. No
      ancestors from the endemic region were traced. The lack of further cases in the
      family is interpreted as indicative of a spontaneous dominant new mutation.

PMID- 7822204
TI  - [Topical therapy of extramammary Paget's disease].
AB  - A case of locally extensive perigenital Paget's disease in an 84-year-old man is
      presented. Topical application of 5-fluorouracil emerged as the safest and most
      effective treatment because of the patient's poor general condition and the
      extensive involvement of the pubic and genital skin.

PMID- 7822205
TI  - [Successful topical treatment of chronic cutaneous leishmaniasis with paromomycin
      sulfate (15%) and methylbenzethonium chloride (12%)].
AB  - A 19-year-old male patient with chronic cutaneous leishmania is was treated
      topically with paromomycin sulphate (15%) and methylbenzethonium chloride (12%)
      in petrolatum album. After application twice daily for two periods of 32 and 44
      days the lesions were completely healed. Previous treatment for 9 months with
      ketoconazole (400 mg/day) together with the topical application of thiabendazole
      (2.5%) in base had been unsuccessful. No major side effects were observed after
      paromomycin sulphate application.

PMID- 7822206
TI  - [Initial visceral involvement with diffuse systemic scleroderma].
AB  - Progressive systemic sclerosis (PSS) is characterized in most patients by
      initially unspecific symptoms like acrocyanosis. Raynaud's phenomenon, general
      malaise or acral paresthesia. Clinical manifestations appear with an edematous
      inflammatory stage of disease leading to a chronic-progressive phase with
      increasing fibrosclerosis of the skin and internal organs. Dermal involvement and
      the demonstration of immunopathological abnormalities in the peripheral blood
      precede visceral fibrosis in most cases. We report on an unusual case of diffuse
      PSS with preceding involvement of internal organs. Early visceral fibrosis is
      demonstrated by histomorphological results and is correlated with laboratory
      findings. Serum antinuclear antibodies could not be obtained until 4 months ante
      finem and the liver was also involved in the fibrotic process.

PMID- 7822207
TI  - [Unilateral eyelid swelling in naevus flammeus faciei. Problems in differential
      diagnosis of unilateral eyelid swelling].
AB  - A 32-year-old white woman presented with persistent swelling of the right upper
      eyelid for diagnosis and therapy. History and physical examination revealed a
      faint nevus flammeus on the right side of her face and neck and bilateral
      blepharochalasis, both of which can produce unilateral periorbital swelling. A
      biopsy taken for histology was diagnostic in this case, since it showed
      lymphoedema secondary to lymphangiectasias associated with the patient's port
      wine stain. Many other possible causes of unilateral lid swelling have to be
      considered and excluded before a definite diagnosis can be established. The
      differential diagnosis is discussed.

PMID- 7822208
TI  - [Gout tophi and Heberden nodules in hyperuricemia].
AB  - The tophus is a characteristic and pathognomonic sign of chronic gout. Before
      effective drugs were available for the treatment of hyperuricaemia about 50-60%
      of patients with gout developed clinically and radiologically apparent urate
      crystal deposits. Clinical cutaneous manifestations of chronic gout are now
      rarely observed. However, the presence of degenerative tissues, as in idiopathic
      osteoarthritis of the fingers, may predispose to the deposition of urate
      crystals. We report on a patient with secondary--probably diuretic-induced-
      hyperuricaemia and gout tophiin Heberden's nodes.

PMID- 7822209
TI  - [Tetracycline-induced pigmentation of the teeth in adults].

PMID- 7822210
TI  - [Report of the 8th Congress of the Study Group "Epidemiology, Biostatistics, and
      Informatics" of the German Dermatologic Society of the Study Circle "Dermatology"
      of the German Society of Medical Informatics, Medical Biometry and Epidemiology
      on 21-22 January 1994 at the Wurzburg University Dermatologic Clinic].

PMID- 7822211
TI  - [Biology of the hair follicle].

PMID- 7822212
TI  - Kinetic microphotometric evaluation of in situ hybridization for mRNA of slow
      myosin heavy chain in type I and C fibres of rabbit muscle.
AB  - The present study was undertaken in order to test the possibility of
      microphotometric evaluation of in situ hybridizations. The histochemical
      detection of mRNA specific to the slow myosin heavy chain (HCI), in fibre cross
      sections of normal and transforming rabbit muscles with a digoxigenin-labelled
      complementary RNA (cRNA) probe was used as a model. Scanning densitometry of
      Northern blot hybridizations showed that the detection of cRNA/mRNA hybrids by a
      staining reaction catalysed by alkaline phosphatase coupled to an anti
      digoxigenin antibody occurs in a concentration-dependent manner and follows a
      linear time course. These findings were the basis for elaborating a comparative
      microphotometric evaluation of in situ hybridization in tissue sections by
      measuring the reaction rate of the alkaline phosphatase-catalysed formazan
      production. Relative amounts of HCI mRNA were thus determined by comparing
      reaction rates instead of by single point microphotometry. This method was
      applied to studies on the distribution of HCI mRNA in different fibre types of
      normal rabbit muscles and and muscles undergoing fast-to-slow fibre
      transformation in response to low-frequency stimulation. The different fibre
      types were identified by histochemical staining for myofibrillar actomyosin
      ATPase (mATPase) in cross sections adjacent to the sections processed for in situ
      hybridization. On the average, type I fibres displayed 2.3-fold higher reaction
      rates than the mean value recorded for C fibres. According to the pronounced
      scattering of the values measured in single C fibres, these fibres represented a
      heterogeneous population in the transforming muscle.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7822213
TI  - Ependyma: phylogenetic evolution of glial fibrillary acidic protein (GFAP) and
      vimentin expression in vertebrate spinal cord.
AB  - The phylogenetic evolution was studied of both glial fibrillary acidic protein
      (GFAP) and vimentin expression in the ependyma of the adult vertebrate spinal
      cord. Eleven species from different vertebrate groups were examined using
      different fixatives and fixation procedures to demonstrate any differences in
      immunoreactivity. GFAP expression in the ependymal cells showed a clear inverse
      relation with phylogenetic evolution because it was more elevated in lower than
      in higher vertebrates. GFAP positive cells can be ependymocytes and tanycytes,
      although depending on their structural characteristics and distribution, the
      scarce GFAP positive ependymal cells in higher vertebrates may be tanycytes.
      Ependymal vimentin expression showed a species-dependent pattern instead of a
      phylogenetic pattern of expression. Vimentin positive ependymal cells were only
      found in fish and rats; in fish, they were tanycytes and were quite scarce, with
      only one or two cells per section being immunostained. However, in the rat spinal
      cord, all the ependymocytes showed positive immunostaining for vimentin. The
      importance of the immunohistochemical procedure, the cellular nature of GFAP
      positive ependymal cells and the relationship between tanycytes and ependymocytes
      are discussed, as well as GFAP and vimentin expression.

PMID- 7822215
TI  - Sensitive detection of human growth hormone mRNA in routinely formalin-fixed,
      paraffin-embedded transgenic mouse tissues by non-isotopic in situ hybridization.
AB  - A sensitive technique of non-isotopic in situ hybridization (NISH) is presented,
      which permits the detection of human growth hormone (hGH) mRNA in routinely
      formalin-fixed, paraffin-embedded transgenic mouse tissues and human post mortem
      pituitaries; the latter were used as positive tissue controls in this study. In
      addition, a double staining procedure combining NISH and immunohistochemistry for
      the visualization of both hGH and hGH mRNA in the same paraffin section is
      described. Digoxigenin-labelled antisense hGH RNA was used for NISH of hGH mRNA.
      The NISH protocol was based upon an established radioactive method. Alkaline
      phosphatase and horseradish peroxidase-based immunoenzymatic procedures for the
      detection of digoxigenin-labelled RNA probes using different chromogens [4-nitro
      blue tetrazolium chloride (NBT), Fast Blue BB, New Fuchsin, and 3,3'
      diaminobenzidine tetrahydrochloride (DAB) with or without intensification of the
      DAB staining] were compared. The proteolytic tissue pretreatment and the
      detection procedure were found to be the most critical steps for successful
      visualization of hGH mRNA. After optimization of the permeabilization conditions,
      hGH mRNA could be visualized in each case studied when alkaline phosphatase/NBT
      based detection was employed. The NISH technique presented here, performed either
      separately or in combination with immunohistochemistry, permits retrospective
      analyses, of hGH (trans)gene expression in archival, paraffin-embedded specimens.

PMID- 7822214
TI  - Thiamine pyrophosphatase cytochemistry in rat endometrium during the oestrous
      cycle.
AB  - The functional morphology of the Golgi apparatus was studied in various types of
      cells in the rat endometrium during the oestrous cycle. A cerium-based enzyme
      cytochemical method was used for the ultrastructural visualization of the
      activity of thiamine pyrophosphatase (TPPase). The cerium-based method was
      evidently superior to the classical lead technique, which was used for
      comparison. TPPase activity in luminal and glandular epithelial cells displayed
      cyclical modulation and redistribution. It was restricted to only one or two
      narrow trans lamellae during dioestrus but extended during proestrus and oestrus
      into nearly all trans-to-cis lamellae of the well-compartmentated Golgi
      apparatus. A homogeneous staining reaction, which was particularly intense during
      the latter two phases and only partly due to unspecific alkaline phosphatase, was
      confined to the apical and basolateral plasma membranes of luminal epithelial
      cells. In the stromal fibroblasts, only one short Golgi saccule was positive at
      dioestrus, whereas three or more trans Golgi lamellae were filled with reaction
      product during oestradiol-dominated oestrus. TPPase activity was furthermore
      observed in the lysosomes in epithelial cells, stromal fibroblasts, capillary
      endothelial cells and pericytes. The present findings of cyclic changes in TPPase
      activity in epithelial cells and stromal fibroblasts provide the first evidence
      of cyclic modulation and redistribution of this enzyme in the endometrium.

PMID- 7822216
TI  - Immunogold localization of TGF beta 1 protein and mRNA in human skin using a
      colloidal gold/digoxygenin system.
AB  - Tissue preservation, and immunogold cytochemical and in-situ hybridization
      labelling intensities vary according to the preparatory protocols used. We wished
      to determine which preparative protocols produce optimal preservation, protein
      and mRNA labelling. Nine combinations of fixative and embedding resin were
      therefore studied using postembedding immunoelectron microscopy and a novel
      immunogold digoxygenin in situ hybridization (ISH) system, to quantitate the
      presence of transforming growth factor beta 1 (TGF beta 1) protein and message in
      human skin. The best preservation was observed in tissue fixed in 1%
      glutaraldehyde and embedded in LR White resin or low acid glycolmethacrylate
      resin (LA-GMA). Preservation was poor in tissue fixed with 1% glutaraldehyde and
      fair in 4% paraformaldeyde, when embedded in Unicryl. Ethanediol dehydration
      coupled with LA-GMA embedding resulted in reasonable preservation. Based on
      quantitative measures of the labelling density for TGF beta 1 protein and mRNA,
      immunogold labelling was adequate with 1% glutaraldehyde fixation coupled with LR
      White or LA-GMA resins, and also with 4% paraformaldehyde and LR White resin, but
      was best with ethanediol dehydration and LA-GMA embedding. ISH labelling under
      basal conditions was best in LA-GMA with 1% glutaraldehyde or 4%
      paraformaldehyde. The ISH label in tissue fixed with 1% glutaraldehyde and
      embedded in LA-GMA was significantly increased by treatment with proteinase K.
      Overall, ethanediol dehydration was associated with a good immunoelectron
      microscopic (IEM) label while LA-GMA with 1% glutaraldehyde or 4%
      paraformaldehyde resulted in a consistently detectable ISH label. LA-GMA
      embedding with 1% glutaraldehyde fixation gave a good result with both IEM and
      ISH labelling.

PMID- 7822217
TI  - Morphological study of rat mast cells stimulated with compound 48/80 at different
      temperatures.
AB  - Changes of mast cells stimulated with compound 48/80 were morphologically
      investigated at different temperatures. Peritoneal mast cells of male rats were
      stimulated in vitro at 4 or 17 degrees C. At 17 degrees C, mast cells stimulated
      for 10 s gave decreased fluorescent reactions for phalloidin. At 30 s
      stimulation, they showed typical exocytosis initiated by fusions of peripherally
      located secretory granules to the plasma membrane. In contrast, mast cells
      stimulated at 4 degrees C exhibited neither decrease of phalloidin reactions nor
      typical excytosis even after 30 s. It was inferred that the fusions were mediated
      by cytoplasmic elements, probably the actin filaments previously suggested to
      prevent release of secretory granules. Furthermore, the space between the
      perigranular membrane and granular contents was enlarged in some mast cells
      stimulated at 4 degrees C. The morphological changes suggested that equivocal
      events occurred also in the cytoplasm of these cells. The mast cells showed no
      typical exocytosis at 4 degrees C.

PMID- 7822218
TI  - Microbial metabolism and biotransformations of styrene.

PMID- 7822219
TI  - Assessment of microwave-based clinical waste decontamination unit.
AB  - A clinical waste decontamination unit that used microwave-generated heat was
      assessed for operator safety and efficacy. Tests with loads artificially
      contaminated with aerosol-forming particles showed that no particles were
      detected outside the machine provided the seals and covers were correctly seated.
      Thermometric measurement of a self-generated steam decontamination cycle was used
      to determine the parameters needed to ensure heat disinfection of the waste
      reception hopper, prior to entry for maintenance or repair. Bacterial and
      thermometric test pieces were passed through the machine within a full load of
      clinical waste. These test pieces, designed to represent a worst case situation,
      were enclosed in aluminium foil to shield them from direct microwave energy. None
      of the 100 bacterial test pieces yielded growth on culture and all 100 thermal
      test pieces achieved temperatures in excess of 99 degrees C during their passage
      through the decontamination unit. It was concluded that this method may be used
      to render safe the bulk of of ward-generated clinical waste.

PMID- 7822220
TI  - Metabolic activities of pseudomonads in batch cultures in extract of minced lamb.
AB  - Pseudomonas fragi, Ps. lundensis and Ps. fluorescens were studied in axenic batch
      cultures growing in a lamb juice (pH 6.0) aerobically or in an atmosphere (Ps.
      fragi only) enriched with carbon dioxide at 4 degrees C. With all but a glucose
      dehydrogenase-deficient strain of Ps. fluorescens there was a sequential
      catabolism of glucose and lactate. Diauxic growth was observed in a nutrient
      deficient meat juice supplemented with glucose and lactate. A transient peak in
      the concentration of gluconate and pyruvate was associated with the catabolism of
      glucose and lactate respectively. With Ps. fluorescens deficient in glucose
      dehydrogenase there was simultaneous catabolism of glucose and lactate. The
      stereoisomers of lactate were catabolized simultaneously in a laboratory medium.
      Glucose-6-phosphate was oxidized to 6-phosphogluconate by Ps. fragi and Ps.
      lundensis under aerobic conditions only. Creatine and creatinine were catabolized
      by Ps. fragi under aerobic conditions only. There was a slight decrease in the
      concentration of total amino acids (ninhydrin-reactive material) during the
      exponential phase of growth. The results suggest that the dominance of Ps. fragi
      in the climax populations in meat is due to catabolism of amino acid related
      substrates, creatine and creatinine.

PMID- 7822221
TI  - A study of the microbiological status of Irish farmhouse cheeses with emphasis on
      selected pathogenic and spoilage micro-organisms.
AB  - Ninety-six 25 g samples from 25 Irish farmhouse cheeses, two Irish non-farmhouse
      cheeses and four foreign cheeses were evaluated for the presence of a variety of
      micro-organisms, namely, coliforms, faecal streptococci, Staphylococcus aureus,
      yeasts, moulds, salmonellas and shigellas. Seventeen cheeses, i.e. the soft and
      semi-soft types, were examined for Listeria monocytogenes. Most of the farmhouse
      cheeses are currently manufactured from raw milk, but some producers now use heat
      treated milk. The incidence of coliforms and faecal coliforms was higher in soft,
      semi-soft and semi-hard cheeses than in hard types. High levels of contamination
      by faecal streptococci and non-pathogenic (coagulase-negative) Staph. aureus
      prevailed in a high proportion of the cheeses. Pathogenic (coagulase-positive)
      staphylococci, however, were also isolated from 50% of the cheeses, some of which
      were manufactured from pasteurized milk. Yeasts were found mainly in
      unpasteurized varieties, especially in the category of soft cheeses. Moulds were
      isolated from five non-mould-ripened cheeses, as well as from mould-ripened
      varieties. Salmonellas, shigellas and Listeria monocytogenes were not detected
      after direct enrichment.

PMID- 7822222
TI  - Bacteriological evaluation of groups of beef carcasses before the wash at six
      Alberta abattoirs.
AB  - A method has been developed for the bacteriological evaluation of groups of beef
      carcasses which can be used to measure the degree of control over hygiene during
      hide removal and carcass dressing in abattoirs. This method, which enumerates
      aerobic mesophilic bacteria automatically using a hydrophobic grid membrane
      filter, was applied at six abattoirs. Two hundred excision samples (5 x 5 x 0.5
      cm) were taken at 10 sites on the external surface of a group of 20 carcasses
      (five carcasses were sampled on each of four consecutive daily visits) for group
      carcass evaluation at each abattoir. For each abattoir, the mean log10 Most
      Probable Number of Growth Units (MPNGU) and between-carcass variance component
      were obtained for each site and the average over sites. Using the average within
      abattoir variance of this study and previously published studies involving 76
      additional carcasses (Jericho et al. 1993), it was determined that 20 carcasses
      are more than adequate to estimate the mean log10 MPNGU per cm2 within 0.5 units
      at a site. The distribution of the log10 MPNGU per cm2 over the 10 sites was
      compared for the abattoirs, and sites were found to cluster into 2-4 homogenous
      groups. The means over sites of log10 MPNGU per cm2 for the abattoirs ranged from
      1.52 to 2.64 and were unrelated to line speed.

PMID- 7822223
TI  - Isolation of a 43 kDa protein from Mycobacterium tuberculosis H37Rv and its
      identification as a pyridine nucleotide transhydrogenase.
AB  - A 43 kDa protein (TB43) was isolated from the cell sonicate (CS) of Mycobacterium
      tuberculosis H37Rv with immobilized metal affinity chromatography (IMAC) on a Ni
      nitrilotriacetic acid column. Two-dimensional electrophoresis of the IMAC
      fraction showed a major spot with an M(r) of 43,000 and a pI of approximately
      6.0. The N-terminal amino acid sequence of TB43 was met-arg-val-gly-ile-pro-asn
      glu-thr-lys-asn-asn-glu-phe-arg-val-ala- ile-thr-pro-ala. It showed 86% homology
      with the N-terminal end of the alanine dehydrogenase of Myco. tuberculosis and
      65% homology with the N-terminal end of the alpha-subunit of the Escherichia coli
      pyridine nucleotide transhydrogenase (Tsh). TB43 did not show any alanine
      dehydrogenase activity and did not react with monoclonal antibody (MAb) HBT10,
      which is known to recognize the 40 kDa alanine dehydrogenase of Myco.
      tuberculosis. It was also not recognized by MAb F29-29 which is known to react
      with a 43 kDa protein of Myco. tuberculosis complex. This protein exhibited
      strong Tsh activity. A similar 43 kDa protein showing Tsh activity was also
      isolated by IMAC from Myco. bovis CS. However, the pI of the protein was
      approximately 7.0. A similar protein could not be isolated from the CS or culture
      filtrate of Myco. bovis BCG and Myco. tuberculosis H37Ra. TB43 is a cell
      associated pyridine nucleotide transhydrogenase and is distinct from the 40/44
      kDa secreted alanine dehydrogenase of Myco. tuberculosis.

PMID- 7822224
TI  - Typing of Clostridium perfringens by in vitro amplification of toxin genes.
AB  - The strains of Clostridium perfringens are classified according to major toxins
      produced. Classically, this determination involves the seroneutralization of
      their lethal effect in mice. However, this method requires specific antisera and
      a large number of mice. In this work, a new typing method was developed based on
      the amplification of toxin genes by polymerase chain reaction (PCR). By
      combination of several pairs of primers, the toxinotype of a Cl. perfringens
      strain was determined by looking at the pattern of bands on an agarose gel
      electrophoresis. This mixture contained primers amplifying simultaneously a part
      of alpha-toxin, beta-toxin, epsilon-toxin and enterotoxin genes. In order to
      distinguish between toxinotype A and E, the l-toxin gene fragment must be
      amplified in a separate PCR reaction. Moreover, with the primers combination, in
      most cases, a PCR product corresponding to the alpha-toxin gene was obtained from
      direct enrichments of animal intestinal contents.

PMID- 7822225
TI  - Oxygen tolerance estimates in Campylobacter species depend on the testing medium.
AB  - Oxygen tolerance of the microaerophile Campylobacter jejuni subsp. jejuni varied
      with different brands of complex media which were used for plating the dilute
      cell suspensions. The tryptone component was one factor. With some tryptones
      growth occurred at 21% oxygen whereas with others there was no growth at oxygen
      levels of 15% or higher. A chemically-defined, agar-solidified plating medium was
      used to estimate the oxygen tolerance of Camp. jejuni subsp. jejuni, Camp. coli
      and Camp. fetus subsp. fetus, and also to assess the effect of added scavengers
      of reactive oxygen intermediates on the oxygen tolerance. Some scavengers such as
      allopurinol, azelaic acid, caffeine, cimetidine, TEMPOL and pyruvate enhanced
      oxygen tolerance markedly whereas others such as carnosine, dimethyl thiourea,
      spermidine and superoxide dismutase had little effect.

PMID- 7822226
TI  - Salvage synthesis of purine nucleotides by Helicobacter pylori.
AB  - The incorporation of purine nucleotide precursors into Helicobacter pylori and
      the activities of enzymes involved in nucleotide salvage biosynthetic pathways
      were investigated by radioactive tracer analysis and nuclear magnetic resonance
      spectroscopy. The organism took up the nucleobases adenine, guanine and
      hypoxanthine, and the nucleosides adenosine, guanosine and deoxyadenosine. Any
      incorporation of deoxyguanosine by the cells was below the detection limits of
      the methods employed. The activities of adenine-, guanine- and hypoxanthine
      phosphoribosyl transferases were established. The bacterium showed high levels of
      adenosine and guanosine nucleosidase activities and lesser activity for
      deoxyadenosine; no hydrolysis of deoxyguanosine was detected. Phosphorylase
      activities were not observed with any of the nucleosides. Phosphotransferase
      activities with similar rates were demonstrated for adenosine, guanosine and
      deoxyadenosine; and a weaker activity was detected for deoxyguanosine. No
      nucleoside kinase activities were observed with any of the nucleosides. The
      presence of adenylate kinase was established, but no guanylate kinase activity
      was observed. The study provided evidence for the presence in H. pylori of
      salvage pathways for the biosynthesis of purine nucleotides.

PMID- 7822227
TI  - Simple method of purification and sequencing of a bacteriocin produced by
      Pediococcus acidilactici UL5.
AB  - A bacteriocin produced by a strain of Pediococcus acidilactici was successfully
      purified sequentially by acid extraction (at pH 2) and reverse-phase high
      performance liquid chromatography (HPLC). Cell extracts of derivative strains
      deficient in bacteriocin production exhibited a similar HPLC elution profile to
      the active extracts except for the two peaks containing bacteriocin activity. The
      sequence of the antibacterial peptide consisted of 44 amino acid residues of
      which 42 were identified, and its molecular weight was 4624 Da, as determined by
      mass spectrometry. Moreover, according to the molecular weight of the peptide,
      the unidentified residues in the bacteriocin sequence must correspond to two
      tryptophan residues, confirming that the peptide isolated from Ped. acidilactici
      UL5 is pediocin PA-1. However, oxidized forms of the bacteriocin produced during
      storage also showed bacteriocin activity and resulted in a second peak with
      activity in the chromatograms. HPLC chromatograms of cell surface preparations
      from the active and from the deficient strains were confirmed by capillary
      electrophoresis. The purification method used is simple and effective in
      comparison with traditional methods, permitting a selective recovery of cell
      associated bacteriocin at low pH, and its isolation in pure form for sequencing.

PMID- 7822228
TI  - Survival of genetically-engineered and wild-type strains of the yeast
      Saccharomyces cerevisiae under simulated environmental conditions: a contribution
      on risk assessment.
AB  - A genetically-engineered strain of Saccharomyces cerevisiae employed for the
      industrial production of the human coagulation Factor XIIIa (rhFXIIIa) was used
      for a survival study under simulated environmental conditions. The homologous
      strain devoid of the recombinant plasmid and the homologous strain bearing the 2
      microns-based vector plasmid without the rhFXIIIa-encoding DNA insert were
      compared. The strains were introduced into natural soil/water suspension, into
      soil/medium suspension and into waste water. After intervals, samples of cell
      suspensions were taken and viable cell numbers were determined by plating on
      antibiotic-containing medium. In addition, a non-radioactive technique involving
      enhanced chemiluminescence was employed to detect plasmid-bearing yeast cells.
      The rhFXIIIa expression plasmid showed a high stability during the simulated
      environmental condition. No differences in survival rates, however, could be
      detected for the plasmid-bearing and plasmid-less strains under the three
      conditions tested, suggesting that the presence of plasmid does not confer
      selective advantages on the survival of the yeast cells. It is concluded that,
      even after accidental release of the engineered yeast cells into the environment,
      elimination rates would be comparable to those for non-recombinant yeast strains.

PMID- 7822229
TI  - Identification of Campylobacter jejuni, Campylobacter coli and campylobacter lari
      by the nucleic acid amplification system NASBAR.
AB  - NASBAR, an isothermal amplification technique for nucleic acids, was evaluated
      for the specific identification of Campylobacter jejuni, Camp. coli and Camp.
      lari. A set of primers and a probe were chosen from the 16S rRNA sequence of
      Campylobacter. The probe was hybridized in solution with the amplified nucleic
      acids of 12 Campylobacter species and nine other Gram-negative bacteria. The
      probe was shown to hybridize specifically to the amplified single-stranded RNA of
      Camp. jejuni, Camp. coli and Camp. lari in an enzyme-linked gel assay (ELGA). In
      a Camp. jejuni model system the combination of NASBAR and ELGA was able to detect
      ca 1000 rRNA molecules. The presence of an excess of Gram-negative bacteria did
      not influence the sensitivity of detection. A number of 6 cfu of Camp. jejuni,
      present in a total count of 4 x 10(6) cfu of Gram-negative bacteria, resulted in
      a positive hybridization signal.

PMID- 7822230
TI  - Effect of heating rate on the thermal inactivation of Listeria monocytogenes.
AB  - In order to quantify the effect of heating rate on the thermal inactivation of
      Listeria monocytogenes an accurate means of describing the inactivation kinetics
      at near instantaneous heating was used. Survivor curves for L. monocytogenes, at
      near instantaneous heating, were obtained over the temperature range 50-64
      degrees C. The use of a linear function to describe the data would have given
      only a poor approximation of the true inactivation kinetics. With a model based
      on a logistic algorithm extremely accurate descriptions were made. In processes
      which had rates of heating < or = 5.0 degrees C min-1, significant deviations of
      real kill from predicted kill were observed. Predicted kill assumed that heating
      rate did not affect the inactivation kinetics of a thermal process. At rates of
      heating between 5.0 and 0.7 degrees C min-1 the deviation greatly increased as
      the rate of heating decreased; approximately a 1.7 x 10(5)-fold difference at 0.7
      degrees C min-1. Maximum thermotolerance was induced at rates of heating < or =
      0.7 degrees C min-1. The increased thermotolerance during slow rates of heating
      was analogous to the induction of the heat-shock response. The models described
      in this work allow for confident assessments of safety to be made not only at
      near instantaneous heating but also when the heating rate varies.

PMID- 7822231
TI  - Microbial succession and intestinal enzyme activities in the developing rat.
AB  - The succession of gut bacteria and selected intestinal enzyme activities in
      developing 7-35-d-old rats was studied. Aerobes and anaerobes were identified as
      members of four broad major bacterial groups, i.e. Gram-positive rods, Gram
      positive cocci, Gram-negative rods and obligate anaerobes. The enzyme activities
      of nitro and azo reductases, beta-glucuronidase, dechlorinase and
      dehydrochlorinase were determined by anaerobic incubation of intestinal
      homogenates with 3,4-dichloronitrobenzene, methyl orange, p-nitrophenyl-beta-D
      glucuronide, and p,p'-DDT respectively. Nitroreductase and azo reductase
      activities increased significantly with the appearance of anaerobes in the large
      intestine. No increase in either nitroreductase or azo reductase activities in
      the small intestine was found. The early and high level of beta-glucuronidase
      activity in the small and large intestines coincided with high numbers of
      coliforms recovered in 7 and 14 d animals. Dehydrochlorinase activity appeared
      early but was undetectable at both 21 and 28 d. Its activity increased at 35 d.
      Dechlorinase activity was variable in development. The rapid changes in the
      microbial flora and intestinal enzyme activities may influence the susceptibility
      of pre-pubescent rats to a variety of toxicants. Therefore, age-dependent
      toxicity may be important in the risk assessment of some environmental chemicals.

PMID- 7822232
TI  - Rapid identification of Aeromonas species using 16S rDNA targeted oligonucleotide
      primers: a molecular approach based on screening of environmental isolates.
AB  - Published 16S rDNA sequencing data for Aeromonas species were analysed and the
      validity of signature sequences derived from our investigations of these
      sequences was examined by sequencing the corresponding 16S rDNA regions of 67
      environmental isolates from sewage effluents and receiving waters around Sydney
      and one clinical isolate, all previously classified as Aeromonas species. Species
      specific probes for Aer. hydrophila and Aer. veronii were designed and tested in
      PCR assays and clearly discriminated these species from the other Aeromonas
      isolates as identified by 16S rDNA sequences.

PMID- 7822233
TI  - Mathematical model of the interactions between Micrococcus spp. and Pseudomonas
      aeruginosa on agar surface.
AB  - The interactions between six different Micrococcus species and two strains of
      Pseudomonas aeruginosa were studied on an agar surface. This type of interaction
      on solid surface could act as a model of situations occurring either in the
      environment, in food or in man. The hypothesis of an amensalistic relationship
      between a Micrococcus spp. and Pseudomonas aeruginosa, due essentially to Ps.
      aeruginosa bacteriolytic enzymes, is retained as the basis for a mathematical
      model of the variations of the colony surface of Micrococcus spp. (S) with
      respect to the distance (d) from Ps. aeruginosa cells. The diffusion of the
      bacteriolytic substance in agar explains the limitation of the growth of the
      Micrococcus spp. This model S = Smax (1-e-md2) is shown to be adapted to all the
      interactions studied.

PMID- 7822234
TI  - Microbial endoglycosidases for analyses of oligosaccharide chains in
      glycoproteins.
AB  - Microbial endoglycosidases are useful for elucidating the structure and function
      of the oligosaccharide chains of glycoconjugates. Most of the microbial endo-beta
      N-acetylglucosaminidases including Endo-H can preferentially act on high-mannose
      type chains of asparagine-linked oligosaccharides of various glycoproteins. Among
      them, Flavobacterium sp. enzyme is produced in large amounts by the inducing
      cultivation. Using this enzyme, the role of oligosaccharide chains in various
      microbial glycoenzymes such as Rhizopus glucoamylase, and yeast invertase was
      examined. The findings suggested that the oligosaccharide chains of them are
      essential participants in the stabilization of the enzyme and in the protection
      from proteolytic inactivation. Novel endo-beta-N-acetylglucosaminidases were also
      found in the culture broths of microorganisms. Unlike most microbial endo-beta-N
      acetylglucosaminidases, Endo-M of Mucor hiemalis could act on a complex type
      oligosaccharide chains, which is similar to Endo-F2 in multiple form of Endo-F
      from Flavobacterium meningosepticum. The complete amino acid sequences of Endo
      F1, -F2, -F3, -H, and Flavobacterium sp. enzyme were determined. All of them had
      two highly conserved regions common to a number of chitinases. Endo-alpha-N
      acetylgalactosaminidase which hydrolyzes the O-glycosidic linkages in
      glycoproteins was found in the culture broth of only a few microorganisms. The
      production of Alcaligenes sp. enzyme was highly induced by the addition of
      porcine gastric mucin in the culture medium. There is some evidence that endo
      alpha-N-acetylgalactosaminidases may recognize not only the glycon but also the
      aglycon amino acids.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7822235
TI  - Local environmental change from the G- to F-form of the actin molecule detected
      on anisotropy decay measurement.
AB  - The fluorescence intensity has been reported to increase 10 to 25 times when N-(1
      pyrene)-iodoacetamide (PIAA)-conjugated actin polymerizes from the G- to the F
      form. To elucidate the molecular mechanism underlying this process, we measured
      the time-averaged anisotropy of PIAA-actin in both the G- and F-forms. The
      anisotropy ratio of PIAA-G-actin (0.137 +/- 0.008) was smaller than that of PIAA
      F-actin (0.221 +/- 0.008). Similar results were obtained when N-(1-pyrene)-3
      iodopropionamide (PIPA), a PIAA analogue with an extra carbon-chain in its
      reactive group, was conjugated with actin. The anisotropy ratio increased from
      0.096 +/- 0.042 to 0.199 +/- 0.035 when PIPA-actin was transformed from the G- to
      the F-form. Further more, we measured the anisotropy decay of PIAA-actin in both
      the G- and F-forms. Least-square fitting revealed that the decay pattern was well
      fitted the wobbling-in-cone model. In the G-form, the pyrene of PIAA actin
      diffused in a cone region with a vertical half angle of 33.4 degrees. This value
      decreased to 25.9 degrees when the actin was transformed to the F-form. Because
      PIAA and PIPA were conjugated at Cys-374 of actin, our results suggest that a
      small cleft exists in the actin molecule in the vicinity of Cys-374, and this
      cleft becomes narrow upon polymerization, resulting in an increase in
      fluorescence intensity.

PMID- 7822236
TI  - Cloning of a mouse Rabphilin-3A expressed in hormone-secreting cells.
AB  - Rab3A, a ras p21-related small GTP-binding protein, is implicated in the
      exocytosis of neurotransmitters. Recently, Rabphilin-3A, a putative target
      protein for Rab3A, was identified and its cDNA has been cloned from bovine brain.
      In this study, we isolated a cDNA encoding a mouse Rabphilin-3A homolog from the
      insulin-secreting cell line, MIN6. Mouse Rabphilin-3A is a protein of 681 amino
      acids exhibiting overall 88.5% identity with bovine Rabphilin-3A. The amino acid
      identity between mouse and bovine Rabphilin-3A is highest in their carboxyl
      terminal halves (97.8% identity) and amino-termini (93.0% identity), which
      contain the region of the two internal repeats homologous to the regulatory
      domain (C2 domain) of protein kinase C and the putative Rab3A-binding region,
      respectively. RNA blot analysis revealed that Rabphilin-3A mRNA is expressed in
      endocrine and hormone-secreting clonal cells, including rat adrenal glands, MIN6,
      the hamster insulin-secreting cell line, HIT-T15, and the rat catecholamine
      secreting cell line, PC12, as well as rat brain. These results suggest that
      Rabphilin-3A might be involved in the exocytosis of secretory vesicles in hormone
      secreting cells as well as in neurons.

PMID- 7822237
TI  - Mutational analysis of the Sar1 protein, a small GTPase which is essential for
      vesicular transport from the endoplasmic reticulum.
AB  - SAR1 encodes a 21-kDa GTPase, which is required for vesicle formation from the
      endoplasmic reticulum in yeast. Although it belongs to the expanding small GTPase
      superfamily, there are interesting structural features that are unique to the
      Sar1 protein. We performed a site-directed mutational study to identify the amino
      acid residues that are essential for the Sar1p function. Among seven mutants we
      constructed, four are functionless by themselves, while two confer temperature
      sensitivity to cells. When the mutant proteins are overproduced in wild-type
      cells, all of these six show a dominant negative effect on cell growth. The
      replacement by serine of the only cysteine residue present in Sar1p caused no
      significant change in the growth phenotype. These findings are not only important
      for analyzing the mechanism of the Sar1p action in yeast, but will also be very
      useful for studying the function of Sar1p counterparts in higher eukaryotes.

PMID- 7822238
TI  - Reconsideration of the essential role of a histidine residue of L-2-halo acid
      dehalogenase.
AB  - His20 of L-2-halo acid dehalogenase from Pseudomonas cepacia MBA4 was suggested
      to serve as a catalytic base [Biochem. J. (1993) 292, 69-74]. In this study, we
      substituted Asn or Leu for His19 of L-2-halo acid dehalogenase from Pseudomonas
      sp. YL, which corresponds to His20 of the P. cepacia enzyme. Although the
      substrate specificity was affected by the substitution, the susceptibilities of
      substrate halo acids were not substantially diminished, and the Km and kcat
      values of the mutant enzymes for L-2-chloropropionate were not significantly
      different from those of the wild-type enzyme. In addition, the wild-type and
      mutant enzymes showed the same pH optimum. Accordingly, His19 is not essential
      for catalysis of L-2-halo acid dehalogenase.

PMID- 7822239
TI  - Indomethacin inhibition of hog gastric H+/K(+)-ATPase arises from its effect on
      both the enzyme protein and the lipid bilayer.
AB  - Indomethacin showed a dose-, time-, and pH-dependent, noncompetitive inhibitory
      effect on hog gastric H+/K(+)-ATPase. Four percent of total indomethacin in the
      buffer (0.20 mmol/liter) bound to the H+/K(+)-ATPase vesicles (15 micrograms/ml).
      It markedly quenched the intrinsic fluorescence of the enzyme, and decreased the
      membrane fluidity. Thus, the inhibitor effect of indomethacin may arise from both
      a direct effect on the hydrolytic and H+ transport functions of the enzyme and a
      disturbing effect on the lipid bilayer of the vesicle.

PMID- 7822240
TI  - Large and cholesteryl ester-rich high-density lipoproteins in cholesteryl ester
      transfer protein (CETP) deficiency can not protect macrophages from cholesterol
      accumulation induced by acetylated low-density lipoproteins.
AB  - High-density lipoprotein (HDL) has been speculated to have an anti-atherogenic
      function. Many in vitro studies have demonstrated that HDL has the ability to
      remove cholesteryl ester (CE) from lipid-laden macrophages. However, the effect
      of alteration in chemical composition and particle diameter on the in vivo
      function of HDL is unknown. In the study described here, we have isolated the HDL
      from patients homozygous for cholesteryl ester transfer protein (CETP) deficiency
      and examined its function in vitro, in order to clarify the anti-atherogenic
      property of HDL in CETP-deficient subjects. Apolipoprotein (apo) E-free HDL2 from
      the patients, separated by heparin-Sepharose column chromatography, was rich in
      CE, poor in triglycerides (TG), and enlarged in size on 4-30% nondenaturing
      polyacrylamide gradient gel electrophoresis. In contrast, HDL3 from the patients
      was normal in size and in its chemical composition. First, we examined the effect
      of HDL on CE accumulation in macrophages. After mouse peritoneal macrophages had
      been incubated with both acetylated low-density lipoproteins (Ac-LDL) and HDL,
      cellular CE content was determined by an enzymatic, fluorometric method. Ac-LDL
      alone induced a 9-fold accumulation of CE. The addition of apo E-free HDL2 and
      HDL3 from controls and patients' HDL3 prevented CE accumulation in macrophages,
      while patients' HDL2 had no preventive effect. We next investigated the in vitro
      ability of HDL to remove cellular CE from lipid-laden macrophages after
      incubation with Ac-LDL. After loading of macrophages with cholesterol by Ac-LDL,
      HDL was added to the culture medium and the cellular CE content was
      measured.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7822241
TI  - Measurement of chlorophyllase activity in olive fruit (Olea europaea).
AB  - Chlorophyllase activity in olive fruit (Olea europaea) was measured using the
      enzyme solubilized from the protein precipitate. The reaction was stopped by
      freezing the mixture at -20 degrees C, to avoid dilution of the sample and
      consequent reduction of the substrate levels to below the detection limits of the
      analytical system. Separation of the substrates and products of the enzymatic
      reaction was performed by reverse-phase HPLC using a gradient solvent system of
      water and ion suppressor/methanol/acetone. These conditions allowed direct
      resolution of the reaction mixture prior to centrifugation, without the need for
      the transfer of any of the components to other solvents. Olive chlorophyllase in
      the crude enzymatic extract showed maximum activity at 50 degrees C and the
      optimum pH was 8.5 in acetate-phosphate-borate buffer for all substrates used,
      chlorophylls (a and b) and pheophytins (a and b). The Km and Vmax values obtained
      for hydrolysis of these substrates showed that chlorophyllase had a greater
      affinity for chlorophyll b, while the highest maximum rate of reaction occurred
      with pheophytin a. Substrate inhibition was observed with pheophytin b.

PMID- 7822242
TI  - Differences related to the production of arachidonic acid between collagen- and
      thrombin-stimulated human platelets.
AB  - The effects of collagen and thrombin on the liberation of free arachidonic acid
      were investigated in human platelets by fluorometric high-performance liquid
      chromatography. Collagen induced a concentration-dependent increase in the extent
      of platelet aggregation, as well as an accumulation of arachidonic acid in human
      platelets. By contrast, thrombin effectively provoked a potent aggregation at
      relatively low concentration without any accumulation of free arachidonic acid,
      although the accumulation of arachidonic acid was detected at a high
      concentration of thrombin (> 0.1 U/ml) that induced full aggregation. The
      selective liberation of arachidonic acid was found in thrombin-stimulated
      platelets. Non-selective liberation of fatty acids occurred in platelets that had
      been stimulated with a high concentration of collagen (10 micrograms/ml), as well
      as in platelets stimulated with A23187. The net amount of free arachidonic acid
      in collagen-stimulated platelets was estimated by use of eicosatetraenoic acid
      (ETYA), which is an inhibitor of both cyclooxygenase and lipoxygenase. ETYA
      markedly potentiated the accumulation of free arachidonic acid in collagen
      stimulated platelets without changing the amounts of other fatty acids in the
      cell.

PMID- 7822243
TI  - Regulation of Ca2+ entry in rat aortic smooth muscle cells in primary culture.
AB  - We characterized Ca2+ entry in rat aortic smooth muscle cells (SMCs) maintained
      in primary culture by measuring uptake of 45Ca2+ or Mn2+ from a normal balanced
      salt solution and the extracellular Ca(2+)-induced increase in the intracellular
      Ca2+ concentration ([Ca2+]i) in a medium [high pH (pH 8.8)/high Mg2+ (20 mM)
      medium containing a sarcoplasmic reticulum Ca(2+)-ATPase inhibitor, thapsigargin]
      that inhibits removal of Ca2+ from the cytoplasm. Such measurements in the
      presence or absence of a dihydropyridine (DHP) calcium channel antagonist (PN200
      110) or hyperpolarizing agent (valinomycin) revealed that DHP-sensitive voltage
      gated Ca2+ channels (VGCCs) are activated in these SMCs under resting conditions
      and that DHP-sensitive Ca2+ entry occurs mostly via these VGCCs. We found that
      receptor stimulation by endothelin-1 in these SMCs resulted in activation of
      neither DHP-sensitive nor -insensitive Ca2+ entry, but rather resulted in marked
      suppression of the former. Utilizing the DHP-sensitive extracellular Ca(2+)
      induced increase in [Ca2+]i as a monitor of activity of the DHP-sensitive VGCCs,
      we investigated the effects of protein kinase activators and phosphatase
      inhibitors on the regulation of these VGCCs. We found that the DHP-sensitive
      VGCCs were inhibited by endothelin-1 through the activation of protein kinase C.
      We also found that they were inhibited by 8Br-cGMP, okadaic acid, and calyculin
      A.

PMID- 7822244
TI  - Specific assay method for the activities of cathepsin L-type cysteine
      proteinases.
AB  - We have established a new differential assay method for cathepsin L-type
      proteinases using specific inhibitors, E-64 for all cysteine proteinases, CA-074
      for cathepsin B, and PLCPI for cathepsin L-type proteinases with Z-Phe-Arg-MCA as
      the substrate. The value of cathepsin B calculated by this method did not
      coincide with value assayed directly in terms of the hydrolysis of Z-Arg-Arg-MCA,
      a specific substrate for cathepsin B. The activities of cathepsin L-type
      proteinases, cathepsins B and J in rat liver and kidney were assayed at the same
      time using this new assay method as a representative example.

PMID- 7822245
TI  - The NhaB Na+/H+ antiporter is essential for intracellular pH regulation under
      alkaline conditions in Escherichia coli.
AB  - We isolated a mutant of Escherichia coli which was defective in an Na+/H+
      antiporter and grew poorly under alkaline conditions [Ishikawa, T., Hama, H.,
      Tsuda, T., and Tsuchiya, T. (1987) J. Biol. Chem. 262, 7443-7446]. Later, it was
      concluded that the defective Na+/H+ antiporter in the mutant was the NhaB system,
      and the nhaB gene was mapped to 25.6 min on the E. coli chromosome [Thelen, P.,
      Tsuchiya, T., and Goldberg, E.B. (1991) J. Bacteriol. 173, 6553-6557]. We found
      that the NhaB-defective cells cannot grow in a high pH medium. Furthermore,
      intracellular pH in the mutant cells was almost the same as extracellular pH
      between 7.9 and 9.1, that is, intracellular pH was not regulated at this pH
      range. On the other hand, intracellular pH of the wild-type cells was maintained
      at about 7.6 when the extracellular pH was between 7.6 and 8.5. Thus, the NhaB
      Na+/H+ antiporter is essential for the regulation of intracellular pH under
      alkaline conditions in E. coli. Introduction of nhaA gene into the mutant cells
      increased Na+/H+ antiporter activity, but did not restore the defective growth
      and defective intracellular pH regulation under alkaline conditions.

PMID- 7822246
TI  - A novel peptide probe for studying the transbilayer movement of
      phosphatidylethanolamine.
AB  - Ro09-0198 is a cyclic peptide isolated from Streptoverticillium
      griseoverticillatum which recognizes strictly the structure of
      phosphatidylethanolamine (PE) and forms an equimolar complex with the
      phospholipid on biological membranes. To use the peptide as a probe for analyzing
      the transbilayer movement of PE, we labeled the amino-terminal amino acid of the
      peptide with biotin without changing either the reactivity or specificity of the
      peptide. The amount of the peptide bound to the membrane was measured by enzyme
      linked immunosorbent assay (ELISA) after extraction of the peptide from the
      membrane. The peptide showed a strict temperature-dependent binding to human
      erythrocytes and the binding increased with increasing temperature. Since the
      peptide bound to PE in a temperature-independent manner and the binding to
      membrane PE is not affected by membrane proteins, the present temperature
      dependent binding of the peptide to the cell membranes was likely to reflect
      temperature-dependent translocation of PE. The binding of the peptide to
      erythrocytes differed greatly among animal species. The peptide also showed
      temperature-dependent binding to a human histocytic lymphoma cell line, U937,
      suggesting that the peptide will provide a novel and convenient probe for
      analyzing the transbilayer movement of PE in eukaryotic cells.

PMID- 7822247
TI  - Chemical structure of a new family of bile pigments from human urine.
AB  - Seven bilirubin metabolites negative to the diazo reaction were identified in the
      urine of healthy persons by enzyme-linked immunosorbent assay (ELISA) using the
      anti-bilirubin monoclonal antibody 24G7. Two of the seven metabolites were
      isolated and their chemical structures were determined using fast-atom
      bombardment-mass spectroscopy (FAB-MS) and 1H-NMR. The two metabolites are
      1,14,15,17-tetrahydro-2,7,13-trimethyl-1,14- dioxo-3-vinyl-16H-tripyrrin-8,12
      dipropionic acid and 1,14,15,17-tetrahydro-3,7,13-trimethyl-1,14-dioxo-2-vinyl
      16H- tripyrrin-8,12-dipropionic acid. They are regioisomers of each other. The
      two bilirubin metabolites are novel tripyrrole biocompounds and belong to a third
      group of bile pigments following biliverdin and bilirubin. We gave these
      compounds the generic names biotripyrrin-a and biotripyrrin-b, respectively.

PMID- 7822248
TI  - Mitogen-activated protein (MAP) kinase phosphorylation of MAP kinase kinase:
      determination of phosphorylation sites by mass spectrometry and site-directed
      mutagenesis.
AB  - Mitogen-activated protein kinase kinase (MKK) phosphorylates and activates
      mitogen-activated protein kinase (MAPK) in response to stimulation of various
      eukaryotic signaling pathways. Conversely, a recent report showed that MAPK
      phosphorylates MKK in vitro [Matsuda, S., Gotoh, Y., and Nishida, E. (1993) J.
      Biol. Chem. 268, 3277-3281]. To gain insight into the function of this feedback
      phosphorylation, we identified the major sites targeted for phosphorylation by
      MAPK and examined whether such a modification plays a role in regulating the
      basal and stimulated MKK activities. Two phosphopeptides generated by tryptic
      digestion of MAPK-phosphorylated MKK were identified by electrospray ionization
      mass spectrometry. Cyanogen bromide cleavage also yielded two phosphopeptides
      whose sequence overlapped with the tryptic phosphopeptides. Both sets of
      phosphopeptides contained candidate MAPK target sites at Thr292 and Thr386 that
      fit the consensus sequence ProXThr*Pro. Replacement of either Thr292 or Thr386
      with alanine by site-directed mutagenesis reduced the phosphate incorporation
      respectively to 32 or 75% that of wild type MKK. Replacement of both threonine
      residues with alanine reduced phosphate incorporation to 2.5% that of wild type
      enzyme. Comparison of MAPK-phosphorylated vs. unphosphorylated MKK showed no
      significant differences in basal or Raf-1-stimulated MKK activity. We conclude
      that the phosphorylation of MKK at Thr292 and Thr386 does not interfere with
      catalysis in vitro.

PMID- 7822249
TI  - Immunochemical evidence for the occurrence of Mu class glutathione S-transferase
      in human fetal livers.
AB  - Immunoblot analysis showed that alpha-class glutathione S-transferase (GST),
      which is one of the major forms in adult human liver, was expressed in human
      fetal liver. Mu-class GST was also expressed in fetal liver. The majority of mu
      class GST expressed in adult liver consisted of a subunit with a molecular weight
      of 27 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS
      PAGE), whereas two subunits of 27 and 26 kDa were detected in fetal liver as
      proteins immunochemically related to mu-class GST. On reverse-phase HPLC, these
      two subunits cross-reactive with antibodies to rat GST 3-3 in fetal liver were
      indistinguishable from each other in their retention time; though, they could be
      separated by chromatofocusing analysis. The molecular weights of GSTs
      immunochemically related to rat GST 3-3, eluted at pH 7.1, 6.4, and 5.7, were 27,
      27 and 26, and 26 kDa, respectively. In addition, the N-terminal amino acid
      sequence of these subunits suggested that GSTs related to rat GST 3-3 expressed
      in fetal liver may be homodimeric and heterodimeric proteins. As expected, pi
      class GST was found to be a major form of GST in fetal liver but not in adult
      liver. In contrast, the GST immunochemically related to rat GST Yrs-Yrs, which is
      classified as theta-class GST, was detected in adult liver but not in fetal
      liver. These results indicate that several isoenzymes of GST are expressed in
      human fetal liver, but they are not the same as those in adult liver.

PMID- 7822250
TI  - Extracellular transport of pseudoazurin of Alcaligenes faecalis in Escherichia
      coli using the COOH-terminal domain of Serratia marcescens serine protease.
AB  - A large COOH-terminal domain of Serratia marcescens serine protease (SSP) is
      essentially required for the excretion of the mature protease region through the
      outer membrane in Escherichia coli. For investigation of the possibility of
      transporting foreign periplasmic proteins by utilizing the function of the COOH
      terminal domain of SSP, the pseudoazurin (PA) gene of Alcaligenes faecalis was
      fused to three different lengths of the COOH-terminal domain via a BglII linker
      sequence (AGATCT) which would be translated into Arg-Ser, one of the cleavage
      sequences of the OmpT protease. The outer membrane fractions of E. coli JM105
      harboring each of the fused genes on a multicopy plasmid was found to contain the
      PA-SSP hybrid protein without the signal sequence as well as the COOH-terminal
      domain of SSP processed at the Arg-Ser sequence. Trypsin-treatment of intact and
      cold osmotically shocked cells suggested that the COOH-terminal domain of SSP in
      the hybrid protein was rigidly integrated in the outer membrane, while the PA
      part of the hybrid protein was exposed on the cell surface. The localization of
      the PA part was confirmed by immunolabelling of intact cells with the anti-PA
      antibody. Furthermore, exogenous addition of purified SSP to the intact E. coli
      cells containing the hybrid protein liberated the PA part from the cells into the
      medium, probably by cleavage at or very near the site processed during the normal
      secretion of intact SSP.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7822251
TI  - The role of human factor X activation peptide in activation of factor X by factor
      IXa.
AB  - We studied the interaction of factor X activation peptide (XAP) with factor IXa
      and factor Xa and the effect of XAP on factor IXa-catalyzed activation of factor
      X. XAP associated with factor Xa in the presence of 5 mM Ca2+ was dissociated
      from factor Xa by gel chromatography using Ultrogel AcA54 in 5 mM EDTA, or in 8 M
      urea-0.1% SDS. An exogenous isolated XAP inhibited the factor IXa-catalyzed
      factor X activation both in the presence and absence of factor VIIIa. 4
      Amidinophenylmethylsulfonyl (aPMS)-factor Xa independent of XAP also inhibited
      the factor X activation more effectively than XAP alone in the presence of factor
      VIIIa. However, aPMS-factor Xa independent of XAP hardly inhibited the factor X
      activation in the absence of factor VIIIa. The binding of 125I-labeled factor X
      to the aPMS-factor IXa fixed to a microwell plate was inhibited by unlabeled
      factor X or XAP, but not by aPMS-factor Xa with or without XAP. Factor IXa
      directly bound to XAP and aPMS-factor Xa with XAP, but did not bind to aPMS
      factor Xa without XAP. These findings suggest that the region of XAP in factor X
      directly interacts with factor IXa, and factor Xa region other than XAP interacts
      with factor VIIIa. Desialation or deletion of N-linked carbohydrates of XAP
      reduced the inhibitory activity of XAP for the factor X activation by factor IXa
      to approximately 50% of that of the intact XAP. This suggests that the sialic
      acids in the carbohydrate chains of the XAP region partly contribute to the
      interaction with factor IXa during its activation.

PMID- 7822252
TI  - Vasoactive intestinal peptide induces tyrosine phosphorylation in PC12h cells.
AB  - Vasoactive intestinal peptide (VIP) is a neuropeptide that induces neuronal
      differentiation through a cAMP-dependent mechanism. We have previously shown that
      VIP induces tyrosine phosphorylation and activation of MAP kinases in PC12h cells
      [J. Biochem. 115, 304-308 (1994)]. In the present study, we showed by Western
      blotting with anti-phosphotyrosine antibodies that in PC12h cells VIP induced
      tyrosine phosphorylation of proteins of 140, 120, 110, and 70 kDa in addition to
      MAP kinases. The immunoprecipitates with anti-phosphotyrosine antibody from VIP
      treated cells contained high activity of protein kinase phosphorylating poly(glu
      tyr) and enolase; the activity from VIP-stimulated cells was 1.5-2 times higher
      than that from unstimulated cells. In vitro kinase reaction without extrinsic
      substrates resulted in tyrosine phosphorylation of doublet proteins which
      migrated slower than pp125FAK on SDS-PAGE. An increase in kinase activity of the
      immunecomplex was detected when the cells were stimulated with forskolin. These
      results suggest that protein tyrosine phosphorylation is involved in
      differentiation of neuronal cells stimulated by VIP and that it is regulated by a
      cAMP-dependent mechanism.

PMID- 7822253
TI  - Depolarization-induced tyrosine phosphorylation in PC12h cells.
AB  - Depolarization induced by KCl was found to induce tyrosine phosphorylation of
      cellular proteins in PC12h cells. By Western blotting with anti-phosphotyrosine
      antibody, we detected tyrosine phosphorylation of proteins with molecular weights
      of 120, 110, 105, 95, 75, 70, 66, 44, and 42 kDa in response to KCl. The
      immunoprecipitates from KCl-treated cells with the antibody contained large
      amounts of tyrosine-phosphorylated proteins and increased activity of tyrosine
      kinase. Incubation of the immunoprecipitates with [gamma-32P]ATP resulted in
      tyrosine phosphorylation of two proteins with the molecular weights of 120 and
      140 kDa. These effects were completely abolished by the addition of EGTA before
      KCl treatment, suggesting that the depolarization-induced tyrosine
      phosphorylation may require calcium entry into the cells from the medium.
      Increased activity of tyrosine kinase phosphorylating the 120 and 140 kDa
      proteins was also recovered from cells stimulated with nerve growth factor, basic
      fibroblast growth factor, epidermal growth factor, and vasoactive intestinal
      peptide. Among them, depolarization by KCl elicited the strongest effect. These
      results indicate that a protein tyrosine kinase that phosphorylate the 120 and
      140 kDa proteins is phosphorylated or activated in response to calcium ion, cAMP,
      and growth factors acting through tyrosine kinase receptors.

PMID- 7822254
TI  - Inhibition of Ca(2+)-induced aggregation of porcine intestinal brush-border
      membranes by lipid peroxidation.
AB  - The effects of lipid peroxidation on Ca(2+)-induced aggregation of porcine
      intestinal brush-border membranes were examined using a system consisting of
      ascorbic acid/Fe2+/tert-butyl hydroperoxide (t-BuOOH). Incubation of the
      membranes with ascorbic acid/Fe2+/t-BuOOH resulted in inhibition of Ca(2+)
      induced aggregation of the membranes with the formation of thiobarbituric acid
      reactive substances, depending on the hydroperoxide concentration and the
      incubation time. The inhibition of the membrane aggregation associated with
      ascorbic acid/Fe2+/t-BuOOH treatment was effectively prevented by the addition of
      an antioxidant, 3(2)-tert-butyl-4-hydroxyanisole, to the reaction mixture.
      Studies with 8-anilino-1-naphthalenesulfonate (ANS) revealed that there is a
      linear relationship between the apparent dissociation constants (Kd) of ANS
      membrane complexes and the aggregating efficiencies of the membranes with
      different levels of lipid peroxidation This suggests that inhibition of the
      membrane aggregation by lipid peroxidation involves a change in the membrane
      surface charge density. Modification of the membranes with malondialdehyde also
      resulted in a decrease in the aggregating efficiency of the membranes with a
      decrease in the Kd value of ANS-membrane complex. In addition, the contribution
      of the lipid organization to membrane aggregation was examined by measuring the
      fluorescence anisotropy of diphenylhexatriene-labeled membranes in the presence
      of a lipid fluidizer, benzyl alcohol. The results are discussed in terms of
      peroxidation-induced inhibition of intramembrane interactions of the membranes.

PMID- 7822255
TI  - Entire nucleotide sequence for Bacillus brevis Nagano Grs2 gene encoding
      gramicidin S synthetase 2: a multifunctional peptide synthetase.
AB  - Bacillus brevis Nagano grs2 gene, which encodes gramicidin S synthetase 2 (GS2)
      catalyzing activation and combination of four constituent amino acids of
      gramicidin S, namely, proline, valine, ornithine, and leucine, has been
      sequenced. The open reading frame of grs2 gene specifies a 4,450-amino acid
      protein with a calculated molecular weight of 508,658. There are four domains
      with a mean of 1,042 amino acid residues containing a repeated sequence of about
      600 amino acids, which is highly homologous to the amino-terminal half of
      gramicidin S synthetase 1 (GS1) (about 40-50% identity). Three domains of grs2
      protein, excluding the first one, show homology over the entire sequences of
      1,042 amino acids, but the first domain only shows homology in the conserved 600
      amino acid sequence. The last 300-amino acid sequence of grs2 protein following
      the fourt domain has no homology with any of the above sequences. Translation
      products of subcloned fragments containing the third or the fourth domain
      catalyzed ornithine- or leucine-dependent ATP-32Pi exchange, respectively. These
      results, together with a previous report on a proline-activation domain indicated
      that the repeated and conserved domains are the individual activation sites of
      the constituent amino acids; the activation sites are arranged in the order of
      peptide elongation on GS2. Several motifs of grs2 protein are conserved among the
      multiple domains of peptide synthetases and aminoacyl or acyl adenylate-forming
      enzymes.

PMID- 7822257
TI  - Purification and characterization of platelet-activating factor acetylhydrolase
      from peritoneal fluid obtained from guinea pigs after endotoxin shock.
AB  - Platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine; PAF)
      acetyl-hydrolase is an enzyme that hydrolyzes the acetyl ester of PAF. We
      purified this enzyme, which accumulated in the peritoneal cavity during endotoxin
      shock, by ammonium sulfate precipitation, and sequential use of butyl-Toyopearl,
      heparin-Sepharose, Con A-Sepharose, chelating-Sepharose, and MonoQ column
      chromatographies. We identified a monomeric polypeptide with a molecular weight
      of approximately 63 kDa on SDS-PAGE. This molecular weight differs from those of
      previously described acetylhydrolases. The purified enzyme did not degrade
      phospholipids with a long chain fatty acyl group at the sn-2 position. In
      addition, the enzyme activity was not inhibited by either pBPB or quinacrine.
      Accordingly, this enzyme is distinct from phospholipase A2. In addition, this
      enzyme also hydrolyzed some oxidatively fragmented phospholipids with PAF-like
      biological activities such as 1-O-hexadecyl-2-glutaroyl-sn-glycero-3
      phosphocholine and 1-O-hexadecyl-2-succinoyl-sn-glycero-3-phosphocholine.

PMID- 7822256
TI  - Accumulation of platelet-activating factor acetylhydrolase in the peritoneal
      cavity of guinea pig after endotoxin shock.
AB  - We examined the production of PAF, a mediator of shock, and LysoPAF, an inactive
      metabolite of PAF, in the guinea pig peritoneal cavity after i.p. administration
      of Escherichia coli LPS. Within 1 h of LPS administration, the level of PAF in
      the peritoneal fluid increased from 4.9 to 37.2 pmol/animal and decreased to the
      control value thereafter. In contrast, the level of lysoPAF gradually rose from
      63.5 to 268 pmol/animal for up to 6 h. The activity of acetylhydrolase, which
      converts PAF to lysoPAF, in the peritoneal cavity increased in parallel with the
      increase in the lysoPAF level. The enzyme was distinguishable from phospholipase
      A2, because p-bromophenacylbromide (p-BPB), Ca2+, and ethylenediaminetetraacetic
      acid (EDTA) did not affect its enzymatic activity. In addition, this
      acetylhydrolase revealed similar biochemical properties to that detected in
      plasma. Both acetylhydrolases were resistant to trypsin treatment and had the
      same apparent molecular weight, as shown by gel-filtration column chromatography.
      These results suggest that the acetylhydrolase, which accumulates in the
      peritoneal cavity, infiltrates from the plasma in response to LPS, and then
      participates in the exclusion of PAF during endotoxin shock.

PMID- 7822258
TI  - 3-Phosphohistidine/6-phospholysine phosphatase from rat brain as acid
      phosphatase.
AB  - A phosphatase hydrolyzing 3-phosphohistidine and 6-phospholysine was purified
      from rat brain cytosol to 90% homogeneity on polyacrylamide gel electrophoresis
      in the presence of sodium dodecyl sulfate. One milligram of protein of the
      purified phosphatase released inorganic phosphate from 3-phosphohistidine, 6
      phospholysine, AMP, GMP, and p-nitrophenyl phosphate at velocities of 6.5, 15.6,
      15.0, 6.9, and 8.3 mumol/min, respectively. However, the purified enzyme could
      not hydrolyze N omega-phosphoarginine and phosphocreatine, which are substrates
      for phosphoamidase [EC 3.9.1.1]. The molecular masses of the holoenzyme and the
      subunit were 94 and 50 kDa, respectively, and the sedimentation coefficient of
      the native enzyme was 6.3 s, indicating that it was a dimeric enzyme of identical
      subunits. The enzyme functioned well under acidic conditions, and 50% of the
      activity was inhibited by 30 microM tartrate, 4 microM vanadate, 20 microM
      molybdate, 4 microM VCl3, or 13 microM MoCl5. These results indicate that the
      present hydrolase belongs to the acid phosphatase group [EC 3.1.3.2].

PMID- 7822259
TI  - Recombinant human tyrosine hydroxylase types 1-4 show regulatory kinetic
      properties for the natural (6R)-tetrahydrobiopterin cofactor.
AB  - Human tyrosine hydroxylase (hTH) exists in four isoforms. The four recombinant
      hTH isoenzymes types 1-4 (hTH1-4) produced in and purified from Escherichia coli
      showed regulatory kinetic properties for the natural (6R)-L-erythro
      tetrahydrobiopterin (RBPH4) as a cofactor. In contrast, the unnatural cofactor
      (6S)-L-erythro-tetrahydrobiopterin (SBPH4) and a synthetic cofactor (6RS)-methyl
      tetrahydropterin (6MPH4) showed usual kinetic characteristics with each of hTH1
      4. Substrate inhibition by tyrosine was observed for each of hTH1-4 with natural
      RBPH4. Two different Km values for pterin cofactor were observed at a high
      concentration (200 microM) of L-tyrosine only with natural RBPH4, in contrast to
      a single Km value for unnatural SBPH4 or synthetic 6MPH4. The present results
      suggest that in the presence of relatively high concentrations (approximately 100
      microM) of tyrosine in vivo, RBPH4 cofactor may have a regulatory role for the
      activity of all four human isoenzymes in vivo. We also found that recombinant
      hTH1 and 3 were more unstable than hTH2 and 4, suggesting that the 4-amino-acid
      insertion in hTH2 and 4 may be responsible for the relative stability of hTH2 and
      4 isoenzymes.

PMID- 7822260
TI  - Production of human salivary type cysteine proteinase inhibitors (cystatins) by
      an Escherichia coli system and partial characterization of recombinant cystatin S
      and its mutant (117 arginine-->tryptophan).
AB  - The cDNAs encoding the precursors of cystatin SN, cystatin S, and two mutants of
      cystatin S (-18R-->W; 117R-->W) were expressed in Escherichia coli JM109 with
      isopropyl-beta-D-thio-galactoside (IPTG) induction. Premature cystatin S with the
      original signal [-20MARPLCTLLLLMATLAGALA] was processed and a large amount of the
      mature form was produced. A mutation (-18R-->W) in the signal reduced its
      accumulation in periplasmic space remarkably. The amount of cystatin SN
      accumulated in the periplasm was slightly smaller than that of cystatin S. The
      periplasmic fraction was prepared by cold osmotic-shock treatment and the
      expressed cystatins were detected using anti-cystatin S antibody. Recombinant
      cystatin S and its mutant (117R-->W) were purified from the periplasmic fractions
      with an ion exchange column of DEAE-cellulose. The amino (N-) terminal 10
      residues of recombinant cystatin S was sequenced to be SSSKEENRII-, which is
      exactly identical to that of the authentic mature cystatin S. Recombinant
      cystatin S and the mutant showed virtually the same inhibitory properties for
      ficin, papain and cathepsin B as the native cystatin S and its monophosphorylated
      form. The inhibitory activity of the both recombinant cystatins for cathepsin C
      was weaker than those of the native cystatin S and phosphorylated cystatin S.

PMID- 7822261
TI  - Electron microscopic filament lengths of connection and its fragments.
AB  - Connectin (titin) is an extraordinarily long filamentous protein of striated
      muscle. The particle lengths of alpha-connectin (titin 1) and its proteolytic
      products, beta-connectin (titin 2) and 1,200 kDa fragment, were measured with
      rotary-shadowed images of the filaments after orientation by centrifugation. It
      was observed that the 1,200 kDa fragment was frequently folded into a double
      strand, beta-connectin was partly folded, and alpha-connectin was easily split
      into beta-connectin and 1,200 kDa fragment. Taking these features into
      consideration, the average lengths of alpha- and beta-connectin and 1,200 kDa
      fragment were estimated to be approximately 1,250, 920, and 360 nm, respectively.

PMID- 7822262
TI  - Tissue distribution of isoforms of type-1 protein phosphatase PP1 in mouse
      tissues and its diabetic alterations.
AB  - The amounts of four isoforms of the catalytic subunit of type-1 protein
      phosphatase, PP1 alpha, PP1 gamma 1, PP1 gamma 2, and PP1 delta have been
      determined in extracts of various mouse tissues including brain, liver, skeletal
      muscle, kidney, small intestine, heart, lung, spleen, thymus, and testis by
      Western blot analysis. Immunoreactive bands for PP1 isoforms were detected at
      39.5, 38.5, and 40 kDa for PP1 alpha, PP1 gamma 1, and PP1 gamma 2, respectively,
      and at 39 and 37 kDa for PP1 delta. The amount of PP1 alpha was at comparable
      levels in all tissues examined except skeletal and heart muscles, in which it was
      detected slightly or not detectable, respectively. The amount of PP1 gamma 1 was
      at higher levels in brain, small intestine, and lung, being 2 to 3 times those in
      other tissues except heart and spleen, in which PP1 gamma 1 was not detectable.
      The amount of PP1 gamma 2 was extremely large in testis, small in brain, lung,
      spleen, and thymus, but it was not detectable in the other tissues. The amount of
      PP1 delta was at comparable levels in all the tissues except skeletal muscle, in
      which it was at a low but detectable level. Then, the amounts of the four PP1
      isoforms were determined in non-obese diabetic (NOD) mice. The amounts of PP1
      alpha were progressively decreased in livers of NOD mice as a function of
      increasing concentrations of blood glucose, whereas the amounts of PP1 gamma 1
      and PP1 delta were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7822263
TI  - cDNA cloning and characterization of mitochondrial import stimulation factor
      (MSF) purified from rat liver cytosol.
AB  - We identified a liver cytosolic protein factor that stimulated the import of
      wheat germ lysate-synthesized precursor proteins into mitochondria. It was termed
      mitochondrial import stimulation factor or MSF [Hachiya, N. et al. (1993) EMBO J.
      12, 1579-1586]. It consisted of 32-kDa (MSFL) and 30-kDa (MSFS) polypeptides as
      assessed by SDS-PAGE. MSF recognized the presequence portion of mitochondrial
      precursor proteins and catalyzed the depolymerization and unfolding of in vitro
      synthesized mitochondrial precursor proteins in an ATP-dependent manner. We
      report here the cDNA cloning and characterization of MSF. Microsequencing of MSFL
      and MSFS showed that they belonged to a highly conserved, widely distributed
      eukaryotic protein family, collectively designated as 14-3-3 proteins. We cloned
      the cDNA of MSFL and that of one component of MSFS (MSFS1) from a rat liver cDNA
      library. The cloned cDNAs were separately expressed in Escherichia coli and the
      expressed proteins were purified to homogeneity. The purified recombinant MSFL
      and MSFS1 stimulated mitochondrial import of adrenodoxin precursor (pAd)
      synthesized in vitro with wheat germ lysate translation system. Recombinant MSFL
      or MSFS1 had the ability to bind with denatured pAd and they kept the precursor
      in an import-competent state. Rabbit polyclonal antibodies raised against the
      recombinant proteins inhibited the import-stimulation activity of rat liver
      cytosol as well as that of authentic purified MSF. Identification of MSF as 14-3
      3 proteins establishes a novel function for this family of proteins and indicates
      their role as cytosolic chaperones to aid many important cellular events.

PMID- 7822264
TI  - Identification of phosphorylation sites on glial fibrillary acidic protein for
      cdc2 kinase and Ca(2+)-calmodulin-dependent protein kinase II.
AB  - We identified the phosphorylation sites of glial fibrillary acidic protein (GFAP)
      for cdc2 kinase and Ca(2+)-calmodulin (CaM)-dependent protein kinase II. GFAP was
      phosphorylated to approximately 0.2 mol of phosphate/mol of GFAP by cdc2 kinase,
      and this phosphorylation did not induce disassembly of the filament structure. On
      the other hand, GFAP was phosphorylated to approximately 1.9 mol of phosphate/mol
      of GFAP by Ca(2+)-CaM-dependent protein kinase II, and this phosphorylation did
      induce disassembly of the filament. Sequential analysis of the purified
      phosphopeptides revealed that only Ser8 on GFAP was phosphorylated by cdc2
      kinase, whereas Ser13, Ser17, Ser34, and Ser389 on GFAP were phosphorylated by
      Ca(2+)-CaM-dependent protein kinase II.

PMID- 7822265
TI  - Phosphocholine-bonded galactosylceramides having a tri-unsaturated long-chain
      base from the clam worm, Marphysa sanguinea.
AB  - Seven glycosphingolipids were obtained in the pure state from the clam worm,
      Marphysa sanguinea, by preparative HPLC with a reversed-phase column in a
      recycling mode. Their structures were elucidated based on detailed analyses of 1H
      and 13C-NMR spectra of the intact compounds. The position and the geometry of
      double bonds in the long-chain base (LCB) were determined by the two-dimensional
      NMR (COSY, NOESY, and HMBC) analyses. All compounds are phosphocholine-bonded
      monogalactosylceramides and two of them have tri-unsaturated long-chain bases.

PMID- 7822266
TI  - Biosynthesis of human endothelins in transformants expressing cDNAs for human
      prepro-endothelins.
AB  - To understand the biosynthesis of the human ET family, three kinds of cloned cDNA
      for human prepro-endothelin-1 (prepro-ET-1), prepro-ET-2, and prepro-ET-3 were
      stably expressed in Chinese hamster ovary cells (CHO-K1). Immunoreactive (ir-) ET
      polypeptides in the culture media of the transformants were purified by reverse
      phase high-performance liquid chromatography (HPLC) coupled with sandwich-type
      enzyme immunoassay (EIA). Amino acid sequencing and FAB mass spectrometry of the
      purified ir-ET polypeptides revealed the presence of human big ET-1 (1-38), big
      ET-2 (1-38), and big ET-3 (1-41)NH2 as intermediate forms. These results directly
      revealed the biosynthetic pathways of three human ETs at the peptide level.

PMID- 7822267
TI  - Serum immunoglobulins in Heymann's experimental nephritis modulate binding of
      properdin and factor-H to sulpho-glycosphingolipids II3SO3(-)-Gg3Cer and III3SO3(
      )-,II3SO3(-)-Gg3Cer.
AB  - The nephropathic effects of Heymann's experimental nephrites involve autoallergic
      serum antibodies directed against rat kidney membrane constituents. In assessing
      the action of glycolipids as possible autoallergens in these conditions, it was
      found that heterologous and autologous Heymann's nephritis sera antibodies
      recognize that rat kidney sulphatides, II3SO3(-)-Gg3Cer (Stri1), and III3SO3(-)
      ,II3SO3(-)-Gg3Cer (Stri2). Two antibody populations in Heymann's sera, each
      reacting with only one of the two sulphatides, could be observed. It was further
      shown that human factor-H and properdin, pivotal regulators of the alternative
      pathway of complement activation, both bound to Stri2 in vitro. This binding of
      factor-H and properdin was differentially affected by affinity-purified anti
      Stri2 antibodies of Heymann's nephritis sera. Whereas the interaction between
      factor-H and Stri2 was inhibited by the antibody, that of properdin was enhanced.

PMID- 7822268
TI  - Purification and characterization of a novel acrosin-like enzyme from boar cauda
      epididymal sperm.
AB  - A trypsin-like protease was extracted with 1% cetyltrimethylammonium bromide
      (CTAB) at pH 7.0 from boar cauda epididymal sperm nuclei whose acrosin had
      previously been removed by acid extraction. The CTAB-extracted sperm protease
      (CSP) was purified by ion-exchange chromatography on CM-23, gel filtration on
      Sephadex G-100, affinity chromatography on benzamidine-CH-Sepharose 4B, and HPLC
      on CM-5PW. CSP is a two chain protein composed of M(r) 2.6K and M(r) 37K chains,
      which are covalently cross-linked by disulfide bonds. CSP exhibited a pH optimum
      between pH 8.0 and 9.0, and was inhibited by diisopropyl phosphorofluoridate,
      antipain, leupeptin, and 1-chloro-3-tosylamide-7-amino-L-2-heptanone. The
      activity of CSP was enhanced about 1.2-fold with 50 mM CaCl2, with which acrosin
      is enhanced 2.0-fold. The catalytic efficiency (kcat/Km) of CSP toward Bz-L-Arg
      OEt, Tos-L-Arg-OMe, and Tos-L-Lys-OMe in the presence of 50 mM CaCl2 differed
      from that of acrosin by factors of 0.53, 1.2, and 0.80, respectively. Amino acid
      sequencing of V8-digested peptides of CSP, and its L- and H-chains showed that
      the amino acid sequence of CSP was closely related to, but different from, that
      of acrosin. These results suggest that CSP is a novel acrosin-like enzyme that
      differs from acrosin in its location in the sperm head, the effect of calcium
      ions on its activity, and its substrate specificity.

PMID- 7822269
TI  - Lipid modifications of trimeric G proteins.
AB  - G protein alpha subunits and beta gamma dimers are covalently modified by lipids.
      The emerging picture is one in which attached lipids provide more than just a
      nonspecific "glue" for sticking G proteins to membranes. We are only beginning to
      understand how different lipid modifications of different G protein subunits
      affect specific protein-protein interactions and localization to specific
      cellular sites. In addition, regulation of these modifications, particularly
      palmitoylation, can provide new ways to regulate signals transmitted by G
      proteins.

PMID- 7822270
TI  - Alternatively spliced juxtamembrane domain of a tyrosine kinase receptor is a
      multifunctional regulatory site. Deletion alters cellular tyrosine
      phosphorylation pattern and facilitates binding of phosphatidylinositol-3-OH
      kinase to the hepatocyte growth factor receptor.
AB  - The hepatocyte growth factor (HGF) receptor is a tyrosine kinase receptor that
      mediates signal transduction upon ligand stimulation. This receptor is present in
      mouse tissues as two major isoforms differing by a 47-amino acid segment in the
      juxtamembrane domain, an alternatively spliced cytoplasmic region adjacent to the
      transmembrane domain of the receptor. We report here that the juxtamembrane
      domain of the receptor is involved in the regulation of downstream signal
      transduction. The two receptor isoforms were transiently expressed in COS-7
      cells. Both exogenous receptors underwent autophosphorylation and subsequently
      stimulated a set of protein tyrosine phosphorylations that were not present in
      control cells. Comparisons of phosphotyrosine profiles of transfected cell
      lysates induced by receptor isoforms demonstrated that at least three
      phosphorylated proteins of approximately 62, approximately 35, and approximately
      30 kDa were differentially induced by the receptor isoforms, suggesting that the
      juxtamembrane domain of a kinase receptor can play a role in selective signal
      transduction. Furthermore, the p85 subunit of phosphatidylinositol-3-OH kinase
      (PI3 kinase) co-precipitated with the small isoform of the HGF receptor, and this
      association was dramatically inhibited by treatment with 12-O
      tetradecanoylphorbol-13-acetate. Since removal of the juxtamembrane domain
      facilitates the binding of p85 to the receptor, it is likely that the
      juxtamembrane region plays a role in negative regulation of the binding of PI3
      kinase to the HGF receptor. Our study establishes novel molecular sequelae of
      alternative splicing of an intracellular domain of the HGF receptor.

PMID- 7822271
TI  - Cloning and characterization of the human megakaryocyte growth and development
      factor (MGDF) gene.
AB  - The megakaryocyte growth and development factor (MGDF) is a cytokine that
      regulates megakaryocyte development and is a ligand for the MPL receptor. In this
      study, we describe the genomic structure of the human MGDF gene. The MGDF gene
      was found to consist of seven exons and six introns spanning 8 kilobases. The
      protein is encoded by exons 3 through 7. The human MGDF gene has been mapped to
      chromosome 3q26.3. In addition to the previously described full-length cDNA, two
      cDNA variants were isolated from human fetal liver. Comparison of these two cDNA
      sequences with the genomic sequence indicates that they arise by differential
      splicing.

PMID- 7822272
TI  - Protective protein as an endogenous endothelin degradation enzyme in human
      tissues.
AB  - An enzyme hydrolyzing the carboxyl terminus of endothelin-1 was detected in
      control human tissues but was deficient in tissues from a patient with
      galactosialidosis, a metabolic disease caused by the protective protein gene
      mutation. It was proportional to the amount of immunologically estimated mature
      protective protein. An antibody against the lysosomal protective protein/beta
      galactosidase complex precipitated the enzyme activity almost completely.
      Transfection of the human cDNA for protective protein resulted in high expression
      of the enzyme activity in transformed fibroblasts from a galactosialidosis
      patient. These results indicated that the mature protective protein is a major
      soluble endogenous endothelin degradation enzyme in human tissues.

PMID- 7822273
TI  - Cysteine 707 is involved in the dehydrogenase activity site of rat 10
      formyltetrahydrofolate dehydrogenase.
AB  - The enzyme, 10-formyltetrahydrofolate dehydrogenase (10-FTHFDH) (EC 1.5.1.6)
      catalyzes both the NADP(+)-dependent oxidation of 10-formyltetrahydrofolate to
      tetrahydrofolate and CO2 and the NADP(+)-independent hydrolysis of 10
      formyltetrahydrofolate to tetrahydrofolate and formate. The COOH-terminal domain
      of the 10-FTHFDH (residues 417-902) shows a 46% identity with a series of NAD(+)
      dependent aldehyde dehydrogenases (EC 1.2.1.3). All known members of the aldehyde
      dehydrogenase family and 10-FTHFDH have a strictly conserved cysteine (Cys-707
      for 10-FTHFDH), which has been predicted to be at the active site of these
      enzymes. Rat liver 10-FTHFDH was expressed in a baculovirus system, and site
      directed mutagenesis has been used to study the role of cysteine 707 in the
      activity of 10-FTHFDH. 10-FTHFDH with alanine substituted for cysteine at
      position 707 had no dehydrogenase activity, while hydrolase activity and binding
      of NADP+ were unchanged. Light scattering analysis revealed that wild type and
      mutant 10-FTHFDH exist as tetramers. We conclude that cysteine 707 is directly
      involved in the active site of 10-FTHFDH responsible for dehydrogenase activity,
      and there is a separate site for the hydrolase activity.

PMID- 7822274
TI  - Structural analysis of myosin heavy chain kinase A from Dictyostelium. Evidence
      for a highly divergent protein kinase domain, an amino-terminal coiled-coil
      domain, and a domain homologous to the beta-subunit of heterotrimeric G proteins.
AB  - We report here the cloning and characterization of the gene encoding the 130-kDa
      myosin heavy chain kinase (MHCK A) from the amoeba Dictyostelium. Previous
      studies have shown that purified MHCK A phosphorylates threonines in the carboxyl
      terminal tail portion of the Dictyostelium myosin II heavy chain and that
      phosphorylation of these sites is critical in regulating the assembly and
      disassembly of myosin II filaments in vitro and in vivo. Biochemical analysis of
      MHCK A, together with analysis of the primary sequence, suggests that the amino
      terminal approximately 500 amino acids form an alpha-helical coiled-coil domain
      and that residues from position approximately 860 to the carboxyl terminus
      (residue 1146) form a domain with significant similarity to the beta-subunit of
      heterotrimeric G proteins. No part of the MHCK A sequence displays significant
      similarity to the catalytic domain of conventional eukaryotic protein kinases.
      However, both native and recombinant MHCK A displayed autophosphorylation
      activity following renaturation from SDS gels, and MHCK A expressed in
      Escherichia coli phosphorylated purified Dictyostelium myosin, confirming that
      MHCK A is a bona fide protein kinase. Cross-linking studies demonstrated that
      native MHCK A is a multimer, consistent with the presence of an amino-terminal
      coiled-coil domain. Southern blot analysis indicates that MHCK A is encoded by a
      single gene that has no detectable introns.

PMID- 7822275
TI  - Evidence for intermediate channeling in mitochondrial beta-oxidation.
AB  - The accumulation of beta-oxidation intermediates was studied by incubating normal
      and beta-oxidation enzyme-deficient human fibroblasts with [2H4]linoleate and L
      carnitine and analyzing the resultant acylcarnitines by tandem mass spectrometry.
      Labeled decenoyl-, octanoyl-, hexanoyl-, and butyrylcarnitines were the only
      intermediates observed with normal cells. Intermediates of longer chain length,
      corresponding to substrates for the beta-oxidation enzymes associated with the
      inner mitochondrial membrane, were not observed unless a cell line was deficient
      in one of these enzymes, such as very-long-chain acyl-CoA dehydrogenase, long
      chain 3-hydroxyacyl-CoA dehydrogenase, or electron transfer flavoprotein
      dehydrogenase. Matrix enzyme deficiencies, such as medium- and short-chain acyl
      CoA dehydrogenases, were characterized by elevated concentrations of
      intermediates corresponding to their respective substrates (octanoyl- and
      decenoylcarnitines in medium-chain acyl-CoA dehydrogenase deficiency and
      butyrylcarnitine in short-chain acyl-CoA dehydrogenase deficiency). These
      observations agree with the notion of intermediate channeling due to the
      organization of beta-oxidation enzymes in complexes. The only exception is the
      incomplete channeling from thiolase to acyl-CoA dehydrogenase in the matrix. This
      situation may be a consequence of only one 3-ketoacyl-CoA thiolase being unable
      to interact with the several acyl-CoA dehydrogenases in the matrix.

PMID- 7822277
TI  - Conservation of a common motif in enzymes catalyzing ADP-ribose transfer.
      Identification of domains in mammalian transferases.
AB  - Bacterial toxin ADP-ribosyltransferases, e.g. diphtheria toxin (DT) and pertussis
      toxin, have in common consensus sequences involved in catalytic activity, which
      are localized to three regions. Region I is notable for a histidine or arginine;
      region II, approximately 50-75 amino acids downstream, is rich in
      aromatic/hydrophobic amino acids; and region III, further downstream, has a
      glutamate and other acidic amino acids. A similar motif was observed in the
      sequence of the glycosylphosphatidylinositol-linked muscle ADP
      ribosyltransferase. Site-directed mutagenesis was performed to verify the role of
      this motif. Proteins were expressed in rat adenocarcinoma cells, released from
      the cell with phosphatidylinositol-specific phospholipase C, and quantified with
      polyclonal antibodies. Transferase His114 in region I aligned with His21 of DT;
      as with DT, the H114N mutant was active. Aromatic/hydrophobic amino acids (region
      II) were found approximately 30-50 amino acids downstream of this histidine.
      Although transferase has a Glu278-Tyr-Ile sequence characteristic of region III
      in DT, Glu278 was not critical for activity. In an alternative region III
      containing Glu238-Glu239-Glu240, Glu238 and Glu240 but not Glu239 were critical.
      Glu240 aligned with critical glutamates in DT, Pseudomonas exotoxin, and C3
      transferase. Thus, the mammalian ADP-ribosyltransferases have motifs similar to
      toxin ADP-ribosyltransferases, suggesting that these sequences are important in
      ADP-ribose transfer reactions.

PMID- 7822276
TI  - The 39-kDa receptor-associated protein modulates lipoprotein catabolism by
      binding to LDL receptors.
AB  - The 39-kDa receptor-associated protein (RAP) is cosynthesized and co-purifies
      with the low density lipoprotein receptor-related protein (LRP)/alpha 2
      macroglobulin receptor and is thought to modulate ligand binding to LRP. In
      addition to binding LRP, RAP binds two other members of the low density
      lipoprotein (LDL) receptor family, gp330 and very low density lipoprotein (VLDL)
      receptors. Here, we show that RAP binds to LDL receptors as well. In normal human
      foreskin fibroblasts, RAP inhibited LDL receptor-mediated binding and catabolism
      of LDL and VLDL with Sf 20-60 or 100-400. RAP inhibited 125I-labeled LDL and Sf
      100-400 lipoprotein binding at 4 degrees C with KI values of 60 and 45 nM,
      respectively. The effective concentrations for 50% inhibition (EC50) of cellular
      degradation of 2.0 nM 125I-labeled LDL, 4.7 nM 125I-labeled Sf 20-60, and 3.6 nM
      125I-labeled Sf 100-400 particles were 40, 70, and 51 nM, respectively. Treatment
      of cells with lovastatin to induce LDL receptors increased cellular binding,
      internalization, and degradation of RAP by 2.3-, 1.7-, and 2.6-fold,
      respectively. In solid-phase assays, RAP bound to partially purified LDL
      receptors in a dose-dependent manner. The dissociation constant (KD) of RAP
      binding to LDL receptors in the solid-phase assay was 250 nM, which is higher
      than that for LRP, gp330, or VLDL receptors in similar assays by a factor of 14
      to 350. Also, RAP inhibited 125I-labeled LDL and Sf 100-400 VLDL binding to LDL
      receptors in solid-phase assays with KI values of 140 and 130 nM, respectively.
      Because LDL bind via apolipoprotein (apo) B100 whereas VLDL bind via apoE, our
      results show that RAP inhibits LDL receptor interactions with both apoB100 and
      apoE. These studies establish that RAP is capable of binding to LDL receptors and
      modulating cellular catabolism of LDL and VLDL by this pathway.

PMID- 7822278
TI  - Thrombin, phorbol ester, and cAMP regulate thrombin receptor protein and mRNA
      expression by different pathways.
AB  - Human mesangial cells have been used to study the regulation of thrombin receptor
      protein and mRNA expression during cross-talk between different signal
      transduction pathways. Persistent activation of thrombin receptor by thrombin led
      to homologous down-regulation of thrombin receptor protein. However, thrombin
      receptor mRNA expression was not affected, suggesting that increased receptor
      degradation is responsible for homologous down-regulation. Chronic activation of
      protein kinase C by phorbol 12-myristate 13-acetate (PMA) and of adenylylcyclase
      by prostaglandin E1 (PGE1) resulted in heterologous down-regulation of thrombin
      receptor protein. In contrast to thrombin, PMA and PGE1 reduced in parallel
      thrombin receptor mRNA levels to 51% and 24% of control, respectively, indicating
      that heterologous down-regulation of thrombin receptor protein is, at least in
      part, due to inhibition of receptor mRNA expression. The mechanisms of
      heterologous down-regulation of thrombin receptor protein have been studied in
      detail and compared to homologous down-regulation. PMA-induced down-regulation
      was completely blocked by GF 109 203 X, an inhibitor of protein kinase C.
      However, the loss of thrombin receptor induced by thrombin was not prevented by
      GF 109 203 X, indicating that homologous regulation is not dependent on protein
      kinase C activation. The heterologous effect of PGE1 was mimicked by 8-bromo
      cAMP, isobutylmethylxanthine, and forskolin, suggesting that an increase in
      intracellular cAMP level is involved in heterologous regulation. Interestingly,
      heterologous down-regulation induced by PGE1 seems not to require previous
      internalization of thrombin receptor. These data indicate that thrombin receptor
      protein and mRNA expression can be regulated in homologous and heterologous ways
      by different mechanisms.

PMID- 7822279
TI  - The transforming receptor tyrosine kinase, Axl, is post-translationally regulated
      by proteolytic cleavage.
AB  - Several receptor tyrosine kinases generate soluble ligand binding domains either
      by differential splicing resulting in a truncated RNA transcript, or by
      proteolytic cleavage. Although the exact role in vivo of these soluble
      extracellular domains is unclear, proteolysis may function to down-regulate the
      receptor, and soluble extracellular domains (ECD) may compete with the intact
      receptor binding to ligand. Axl is a member of a new class of receptor tyrosine
      kinases characterized by an ECD resembling cell adhesion molecules and unique
      sequences in the kinase domain. In addition, Axl is transforming in both
      fibroblast and hematopoietic cells, and appears to be involved in mesenchymal
      development. We now find that Axl is post-translationally processed by cleavage
      in a 14 amino acid region immediately NH2-terminal to the transmembrane domain
      resulting in a soluble ECD and a membrane bound kinase domain. The sequence of
      this putative cleavage site shares no homology with recognition sites of known
      proteases. Characterization of this proteolytic processing shows that it does not
      require protein synthesis or transport but is augmented by phorbol ester
      treatment. Since the cleavage of Axl enhances turnover of the kinase on the cell
      surface, we suggest that proteolytic processing down-regulates Axl kinase
      activity.

PMID- 7822280
TI  - A limulus intracellular coagulation inhibitor type 2. Purification,
      characterization, cDNA cloning, and tissue localization.
AB  - We described in a foregoing report findings on serpin, a serine protease
      inhibitor, newly identified in horseshoe crab (Tachypleus tridentatus) hemocytes
      and we name it limulus intracellular coagulation inhibitor, LICI (Miura, Y.,
      Kawabata, S., and Iwanaga, S. (1994) J. Biol. Chem. 269, 542-547). This serpin
      specifically inhibits limulus lipopolysaccharide-sensitive serine protease,
      factor C. In ongoing studies on limulus serpin, we have found another inhibitor,
      LICI type-2 (LICI-2), which inhibits not only factor C (k1 = 7.1 x 10(4) M-1 S-1)
      but also limulus clotting enzyme (k1 = 4.3 x 10(5) M-1 S-1). LICI-2 inhibits
      mammalian serine proteases, including alpha-thrombin, salivary kallikrein,
      plasmin, and tissue plasminogen activator. The inactivation of plasmin is the
      most rapid (k1 = 1.2 x 10(6) M-1 S-1). The purified LICI-2 is a single chain
      glycoprotein with an apparent M(r) = 42,000. A cDNA for LICI-2 was isolated and
      the open reading frame coded for a mature protein of 386 amino acids, of which
      160 residues were confirmed by peptide sequencing. Although LICI-2 shows
      significant sequence similarity to the previous limulus serpin, LICI-1 (42%
      identity), LICI-2 contains a unique putative reactive site, -Lys-Ser-, distinct
      from that of LICI-1 (-Arg-Ser-). Northern blotting revealed expression of LICI-2
      mRNA only in hemocytes, and not in heart, brain, stomach, intestine, coxal gland,
      and skeletal muscle. The immunoblot of large and small granule components with
      antiserum against purified LICI-2 suggests that LICI-2 is stored specifically in
      large granules, as in the case of LICI-1, and is released in response to external
      stimuli. We propose that the LICIs be classified into a new subfamily of
      intracellular serpins, regulated secretory serpins.

PMID- 7822281
TI  - Isoprenylation of plant proteins in vivo. Isoprenylated proteins are abundant in
      the mitochondria and nuclei of spinach.
AB  - Protein isoprenylation in vivo is demonstrated using spinach seedlings labeled
      with [3H]mevalonate. This report provides evidence for the occurrence of a large
      number of isoprenylated proteins in plants. Seedlings, without roots, were
      labeled quantitatively through the cut stem. Mevinolin treatment of the seedlings
      resulted in increased incorporation of radiolabel into proteins. Approximately 30
      labeled bands could be detected after autoradiography of SDS-polyacrylamide gel
      electrophoresis-separated polypeptides, ranging in molecular mass from 6 to 200
      kDa. Methyl iodide hydrolysis resulted in the release of covalently bound
      farnesol, geranylgeraniol, phytol, and some unidentified isoprenoid compounds
      from mevalonate-labeled proteins. It was found that all cellular fractions
      contained some isoprenylated proteins, although most were located in the
      mitochondria and nuclei. Subfractionation of the nucleus revealed that the
      majority of isoprenylated proteins in this compartment were components of the
      nuclear matrix. The results demonstrate that in vivo labeling of a complex
      organism can be performed using a plant system in order to study protein
      isoprenylation and distribution of modified proteins in different cellular
      compartments.

PMID- 7822282
TI  - Structure of metal site in azurin, Met121 mutants of azurin, and stellacyanin
      investigated by 111mCd perturbed angular correlation (PAC).
AB  - The geometries of the metal sites in cadmium-substituted azurins have been
      investigated by 111mCd perturbed angular correlation (PAC). The study includes
      wild type azurin as well as Met121 mutants of azurin, where methionine has been
      substituted by Ala, Asn, Asp, Gln, Glu, and Leu. The nuclear quadrupole
      interaction of wild type azurin analyzed in the angular overlap model is well
      described as coordination of His46, His117, and Cys112 and cannot be described by
      coordination of Met121 and/or Gly45. For most of the mutants, there exist two
      coordination geometries of the cadmium ion. With the exception of the Glu and Asp
      mutants, one of the conformations is similar to the wild type conformation. The
      other coordination geometries are either best described by a coordinating water
      molecule close to the original methionine position or by coordination by the
      substituting amino acid. These experiments show that even though the methionine
      does not coordinate it plays an important role for the geometry of the metal
      site. The nuclear quadrupole interaction of stellacyanin was also measured. The
      value resembles the most prominent nuclear quadrupole interaction of the Met121-
      >Gln mutant of Alcaligenes denitrificans azurin, indicating that the structures
      of the two metal sites are similar.

PMID- 7822283
TI  - Agonist-induced desensitization of the mu opioid receptor-coupled potassium
      channel (GIRK1).
AB  - In Xenopus oocytes expressing the rat mu receptor and the G protein-gated,
      inwardly rectifying K+ channel (known as KGA or GIRK1), application of [D
      Ala2,MePhe4,Glyol5]enkephalin) a mu opioid agonist, evoked a dose-dependent
      increase in K+ conductance. With sustained agonist exposure, the amplitude of the
      response decayed with a t1/2 of 8 +/- 2 min. In oocytes coexpressing the mu and
      5HT1A receptors with GIRK1, stimulation of either receptor resulted in
      heterologous desensitization of the subsequent response to the other. Injection
      of guanosine 5'-O-(thiotriphosphate) (1 mM) increased the basal GIRK1 activity
      and the total response to the application of agonist, but did not affect the rate
      of desensitization. Basal channel activity in the absence of agonist also
      desensitized at the same rate when the oocytes were exposed to high K+ (96 mM)
      solution. The above results indicate that the desensitization of the response
      occurred at a site downstream of the receptor, possibly at the channel. The rate
      of desensitization was not significantly altered by any of the following
      treatments: removal of external Ca2+, preloading the oocytes with 1,2-bis(o
      aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-tetra-(acetoxymethyl)-ester (0.5-1
      mM), elevation of cAMP levels, treatment with phorbol esters (1 microM),
      staurosporine (0.5 microM), okadaic acid (1 microM), or cytochalasin B (0.5
      microM). These results suggest that desensitization may not involve a calcium or
      phosphorylation-dependent mechanism.

PMID- 7822284
TI  - The pH-sensitive actin-binding protein hisactophilin of Dictyostelium exists in
      two isoforms which both are myristoylated and distributed between plasma membrane
      and cytoplasm.
AB  - The histidine-rich protein hisactophilin is known to be associated with the inner
      surface of the plasma membrane and to be present as a soluble protein in the
      cytoplasm of Dictyostelium discoideum cells. Mass spectrometry of hisactophilin
      from the cytosol or extracted from a membrane fraction showed that none of the
      hisactophilin purified from D. discoideum cells had the mass predicted from the
      known cDNA-derived amino acid sequence of the protein. Electrospray mass
      spectrometry and liquid secondary ion mass spectrometry of tryptic fragments
      separated by reversed-phase high performance liquid chromatography (HPLC)
      identified the most hydrophobic peptide as a myristoylated fragment from the N
      terminus of hisactophilin. Taken together the analytical data, it is concluded
      that all hisactophilin in D. discoideum cells is N terminally modified by
      myristoylation. By reversed-phase HPLC, two isoforms of hisactophilin, HsI and
      HsII, were recovered from the cytosolic as well as the membrane fraction of D.
      discoideum cells. Whereas the masses of HsI fragments produced by trypsin fit
      into the previously published sequence of hisactophilin (myristoylation
      considered), HsII is another protein distinguished from HsI by several amino acid
      exchanges. HsI and HsII can form homo- and heterodimers by disulfide bridges.
      Hisactophilin is phosphorylated in vivo. Both isoforms proved to be substrates of
      membrane-associated threonine/serine kinase from D. discoideum, which may
      regulate the interaction of hisactophilin with the plasma membrane.

PMID- 7822285
TI  - Biological activation of pro-HGF (hepatocyte growth factor) by urokinase is
      controlled by a stoichiometric reaction.
AB  - Hepatocyte growth factor (HGF) is a paracrine inducer of morphogenesis and
      invasive growth in epithelial and endothelial cells. HGF is secreted by
      mesenchymal cells as an inactive precursor (pro-HGF). The crucial step for HGF
      activation is the extracellular hydrolysis of the Arg494-Val495 bond, which
      converts pro-HGF into alpha beta-HGF, the high-affinity ligand for the Met
      receptor. We previously reported that the urokinase-type plasminogen activator
      (uPA) activates pro-HGF in vitro. We now show that this is a stoichiometric
      reaction, and provide evidence for its occurrence in tissue culture. Activation
      involves the formation of a stable complex between pro-HGF and uPA. This complex
      was isolated from the in vitro reaction of pure uPA with recombinant pro-HGF, as
      well as from the membrane of target cells, after sequential addition of uPA and
      pro-HGF. On the cell membrane, the uPA-HGF complex was bound to the Met receptor.
      Monocytic cell lines, and primary monocytes after adhesion, activated efficiently
      pro-HGF both on their surface and in the culture medium. This activation was
      inhibited by anti-catalytic anti-uPA antibodies, and occurred by a stoichiometric
      reaction. The stoichiometry of the activation reaction suggests that the
      biological effects of HGF can be titrated in vivo by the level of uPA activity.
      Adequate amounts of uPA can be locally provided by the macrophages, which would
      condition the tissue microenvironment by rendering HGF bioavailable to its target
      cells.

PMID- 7822286
TI  - Defective binding of neutral lipids by a carboxyl-terminal deletion mutant of
      cholesteryl ester transfer protein. Evidence for a carboxyl-terminal cholesteryl
      ester binding site essential for neutral lipid transfer activity.
AB  - The plasma cholesteryl ester transfer protein (CETP, 476 amino acids) transfers
      cholesteryl ester (CE) from high density lipoprotein (HDL) to triglyceride-rich
      lipoproteins and plays a major role in HDL catabolism. Using deletional and site
      directed mutagenesis, we previously showed that the carboxyl terminus of human
      CETP comprises the epitope of a neutralizing monoclonal antibody and is necessary
      for neutral lipid transfer activity. To assess the nature of the involvement of
      the COOH terminus in cholesteryl ester transfer activity, we characterized a
      deletion mutant of CETP lacking amino acid residues 470-475 in terms of CE
      transfer kinetics, association with HDL, and capacity to bind CE, triglyceride
      (TG), and phosphatidylcholine (PC). Kinetic analysis indicated a major catalytic
      defect of the deletion mutant, as shown by markedly decreased maximum cholesteryl
      ester transfer activities (apparent Vmax) for donor (HDL) and acceptor (low
      density lipoprotein (LDL)) lipoproteins but there were no significant changes of
      concentrations of the donor and acceptor at 50% Vmax (apparent Km). The binding
      of CETP to HDL, as determined by native gel electrophoresis, was similar for wild
      type and mutant protein. When egg PC/CE vesicles were incubated with wild type
      CETP and then separated by gel filtration chromatography, there was maximum
      binding of about 1 mol of CE/mol of CETP. Under similar conditions the mutant
      CETP bound 0.09-0.37 mol of CE/mol of protein. Similarly, when egg PC/TG vesicles
      were incubated with the CETP proteins, there was a maximum binding of 0.5 mol of
      triglyceride/mol of wild-type CETP, whereas there was only 0.00-0.07 mol of
      TG/mol of deletion mutant. The binding of phosphatidylcholine was similar for
      wild-type and the deletion mutant. The studies suggest that amino acids 470-475
      (forming part of a COOH-terminal amphipathic helix) are involved in CE and TG
      binding by CETP but are not required either for the binding of PC by CETP or the
      association of CETP with HDL. The COOH terminus of CETP may comprise a neutral
      lipid binding site directly involved in the lipid transfer mechanism.

PMID- 7822287
TI  - Stoichiometric interaction of the epidermal growth factor receptor with the
      clathrin-associated protein complex AP-2.
AB  - Plasma membrane clathrin-associated protein complexes (AP-2) have been shown to
      co-immunoprecipitate with the epidermal growth factor (EGF) receptor (Sorkin A.,
      and Carpenter, G. (1993) Science 261, 612-615). Hence, we analyzed the
      stoichiometry of the EGF receptor interaction with AP-2 using a new antibody that
      efficiently immunoprecipitates native AP-2. EGF receptor AP-2 complexes were
      isolated from 35S-labeled cells treated with EGF by EGF receptor affinity
      chromatography followed by precipitation with the antibody to AP-2. Quantitation
      of the relative molar concentrations of the proteins found in the complex
      revealed that 1 mol of AP-2 was associated with approximately 1.1 mol of EGF
      receptor. No other proteins were present in significant molar concentrations
      relative to AP-2, indicating that other proteins are not stoichiometrically
      involved in the interaction of EGF receptors and AP-2 in vivo. Co
      immunoprecipitation experiments in cells expressing a mutant EGF receptor
      demonstrated that the cytoplasmic carboxyl-terminal 214 residues of the EGF
      receptor are essential for interaction with AP-2.

PMID- 7822288
TI  - Interactions among proteins involved in bud-site selection and bud-site assembly
      in Saccharomyces cerevisiae.
AB  - Bud formation in yeast involves the actions of the Ras-type GTPase Rsr1, which is
      required for the proper selection of the bud site, and the Rho-type GTPase Cdc42,
      which is necessary for the assembly of cytoskeletal structures at that site. The
      Cdc24 protein is required both for proper bud-site selection and bud-site
      assembly and has been recently shown to display guanine-nucleotide-exchange
      factor (GEF) activity toward Cdc42. Here, we demonstrate, using recombinant
      proteins, that Cdc24 can also bind directly to Rsr1. This binding has no effect
      on the ability of Rsr1 to undergo intrinsic or GEF-stimulated GDP-GTP exchange.
      However, Cdc24 can inhibit both the intrinsic and GTPase-activating protein
      stimulated GTPase activity of Rsr1 and thereby acts as a GTPase-inhibitor protein
      for Rsr1. Cdc24 thus appears to bind preferentially to the activated form of
      Rsr1. The SH3 domain-containing bud-site assembly protein Bem1 also binds
      directly to Cdc24, and we show here that this interaction is inhibited by Ca2+.
      Neither Bem1 nor Cdc42 affects the GTPase-inhibitor protein activity of Cdc24
      toward Rsr1, and neither Bem1 nor Rsr1 affects the GEF activity of Cdc24 toward
      Cdc42. Taken together, these results suggest that Cdc24 enables the direct
      convergence of a Ras-like protein (Rsr1) and a Rho-like protein (Cdc42) with the
      SH3-domain-containing protein (Bem1) and that independent domains of Cdc24 are
      responsible for these different interactions. These results also suggest that
      rather than directly controlling the GEF activity of Cdc24, the primary roles of
      Rsr1 and Bem1 might be to control the positioning of Cdc24 within the cell.

PMID- 7822289
TI  - Functional compartmentation of dCTP pools. Preferential utilization of salvaged
      deoxycytidine for DNA repair in human lymphoblasts.
AB  - The utilization of dCTP derived from de novo synthesis through ribonucleotide
      reductase in exponentially growing CCRF-CEM cells was compared with the metabolic
      fate of dCTP produced by the salvage pathway. Exogenous dCyd was not effectively
      incorporated into replicating DNA; instead, dCTP derived from ribonucleotide
      reductase (labeled by [5-3H]Cyd) was the main precursor for that purpose,
      apparently because of functional compartmentation of the dCTP pool in these
      cells. Studies of the metabolic route of incorporation of exogenous [5-3H]dCyd
      into DNA of growing CCRF-CEM cells demonstrated that it was mainly incorporated
      through the DNA repair pathway. Incorporation of [5-3H]dCyd into DNA of
      synchronized cell populations was maximal in G1 cells, whereas [3H]dThd
      incorporation occurred predominantly in S phase cells. When cellular DNA was
      density labeled by incubation with BrdUrd, repaired DNA, which was less dense
      than replicated DNA, was preferentially labeled by [5-3H]dCyd. In contrast,
      replicated DNA was labeled by both [3H]dThd and [5-3H]Cyd. The DNA-damaging
      agents methylmethanesulfonate, ultraviolet irradiation, and gamma-irradiation
      inhibited [3H]dThd incorporation, whereas they stimulated the accumulation of [5
      3H]dCyd in DNA. Based on these results, we propose that the dCTP pool is
      functionally compartmentalized in growing CCRF-CEM cells. dCTP derived from the
      salvage pathway is utilized predominantly for DNA repair, whereas the de novo
      pathway supplies dCTP for DNA replication.

PMID- 7822290
TI  - Utilization of aspartate as a nitrogen source in Escherichia coli. Analysis of
      nitrogen flow and characterization of the products of aspartate catabolism.
AB  - 15N NMR, reverse-phase high performance liquid chromatography and gas
      chromatography/mass spectrometry have been used to follow nitrogen metabolism in
      Escherichia coli labeled on medium containing L-[15N]aspartate. The flow of 15N
      through various nitrogen-containing metabolites was followed over the course of
      the labeling period. For wild-type E. coli labeled on L-[15N]aspartate as sole
      source of nitrogen, significant 15N labeling was detected only in the
      intracellular L-glutamate, L-alanine, L-aspartate, and putrescine pools.
      Intracellular concentrations of L-aspartate and L-glutamate differed
      significantly in extracts of an arginine auxotroph (argG-), which is deficient in
      a potential aspartate-assimilating reaction. When the L-[15N]aspartate containing
      labeling medium was supplemented with unlabeled arginine, extracts of wild-type
      E. coli were shown to contain significant amounts of unlabeled ammonia and
      putrescine. There was substantial dilution of 15N in the glutamate pool. The
      observation that glutamate, aspartate, and alanine are 15N-labeled, but ammonia
      is not, suggests that these amino acids are not the immediate source of ammonia.
      Our results suggest that arginine may be an intermediate for the degradation of
      some of the aspartate and that arginine may be an intermediate for ammonia
      production during nitrogen-limited growth. Our results also strongly suggest the
      presence of a previously uncharacterized pathway of arginine degradation.

PMID- 7822291
TI  - Insulin regulates transcription of the CCAAT/enhancer binding protein (C/EBP)
      alpha, beta, and delta genes in fully-differentiated 3T3-L1 adipocytes.
AB  - The effect of insulin on expression of CCAAT/enhancer binding protein (C/EBP)
      alpha, beta, and delta was investigated in fully-differentiated 3T3-L1
      adipocytes. Treatment of adipocytes with insulin stimulated rapid
      dephosphorylation of C/EBP alpha, and repressed the expression of C/EBP alpha
      within 2-4 h, with > 90% suppression occurring at 24 h. While insulin induced
      expression of C/EBP beta and C/EBP delta within 1 h and caused a > 20-fold
      increase by 4 h, expression returned to nearly pretreatment levels by 24 h. The
      insulin concentration dependence of these effects was consistent with involvement
      of the insulin receptor. Gel shift analysis revealed that 6 h of insulin
      treatment decreased the binding of nuclear C/EBP alpha while increasing binding
      of nuclear C/EBP beta and C/EBP delta. The reciprocal effects of insulin on the
      steady-state levels of C/EBP transcription factors can be accounted for
      kinetically and quantitatively by changes in their mRNA levels, which can be
      accounted for by effects on gene transcription. The effects of insulin on
      adipocyte gene transcription (e.g. GLUT4) may be mediated, at least in part, by
      down-regulation of C/EBP alpha and/or its dephosphorylation.

PMID- 7822292
TI  - A non-peptide mimetic of Ras-CAAX: selective inhibition of farnesyltransferase
      and Ras processing.
AB  - Cysteine farnesylation of the carboxyl-terminal tetrapeptide CAAX (C = Cys, A =
      Leu, Ile, or Val, X = Met or Ser) of the oncogene product Ras is required for its
      malignant transformation activity. As a consequence farnesyltransferase (FTase),
      the enzyme responsible for this lipid modification, has become one of the most
      sought-after targets for anticancer drug development. We have recently designed
      peptide mimics of the COOH-terminal Cys-Val-Ile-Met of KB-Ras where the dipeptide
      Val-Ile was replaced by aminobenzoic acid derivatives. Although these
      peptidomimetics are potent inhibitors of FTase in vitro, they retain several
      undesirable peptide features that hamper their use in vivo. We report here the
      design, synthesis, and biological activity of the first non-peptide mimetics of
      CAAX where the tripeptide AAX was replaced by biphenyl derivatives. (R)-4-[N-(3
      mercapto-2-aminopropyl)]amino-3'- carboxybiphenyl, where the cysteine is linked
      to the biphenyl derivative through a secondary amine, contains no amino acids,
      lacks peptidic features, and has no hydrolyzable bonds. This peptidomimetic is a
      potent inhibitor of FTase in vitro (IC50 = 50-150 nM) and disrupts Ras processing
      in whole cells. Furthermore, this non-peptide mimetic of CAAX is highly selective
      for FTase (666-fold) relative to the closely related geranylgeranyltransferase I.
      This selectivity is also respected in vivo since the processing of Ras but not
      the geranylgeranylated Rap1A was disrupted in whole cells. Structure activity
      relationship studies revealed that FTase recognition and inhibitory potency of
      CAAX peptidomimetics require free thiol and carboxylate groups separated by a
      hydrophobic moiety, and that precise positioning of these functional groups must
      correspond to that of the parent CAAX. The true CAAX peptidomimetic described in
      this manuscript has several desirable features for further development as a
      potential anticancer agent. It is not metabolically inactivated by FTase, does
      not require a pro-drug strategy for inhibition in vivo, and is selective for
      farnesylation relative to geranylgeranylation.

PMID- 7822293
TI  - Role of clathrin-coated vesicles in glycoprotein transport from the cell surface
      to the Golgi complex.
AB  - Plasma membrane glycoproteins recycle to the Golgi complex, but the route
      followed by these proteins is not known. To elucidate the pathway of transport,
      the involvement of clathrin-coated vesicles was tested. This was accomplished by
      comparing the traffic of wild type low density lipoprotein receptor (LDLR) and FH
      683, a mutant receptor whose endocytosis from the cell surface in coated vesicles
      is reduced by 90-95%. Wild type LDLR traveled from the cell surface to the
      sialyltransferase compartment of the Golgi with a half-time of 2.5 h in K562
      human leukemia cells expressing receptor from a transfected cDNA. In contrast, FH
      683 LDLR recycled to the Golgi at 33% of the wild type rate, suggesting that wild
      type LDLR is largely transported to the Golgi by a pathway that involves clathrin
      coated vesicles. Moreover, because clathrin-coated vesicles that bud from the
      plasma membrane are transported to endosomes, surface-to-Golgi transport probably
      involves an endosomal intermediate. Finally, because there was substantial
      transport of mutant LDLR to the Golgi even though its endocytosis in coated
      vesicles was greatly reduced, there may be a second pathway of surface-to-Golgi
      traffic. Our results suggest that wild type LDLR may move from plasma membrane to
      Golgi by two routes. Two-thirds of the traffic proceeds via a coated vesicle
      mediated pathway while the remainder may follow a clathrin-independent pathway.

PMID- 7822295
TI  - Active site mutations of Pseudomonas aeruginosa exotoxin A. Analysis of the
      His440 residue.
AB  - Pseudomonas aeruginosa exotoxin A (ETA) is a member of the family of bacterial
      ADP-ribosylating toxins which use NAD+ as the ADP-ribose donor. By analogy to
      diphtheria and pertussis toxins, the His440 residue of ETA has been proposed to
      be one of the critical residues within the active site of the toxin. In this
      study the role of the His440 residue was explored through site-directed
      mutagenesis which resulted in the production of ETA proteins containing Ala, Asn,
      and Phe substitutions at the 440 position. The His440-substituted ETA proteins
      were purified and analyzed. All substitutions at the 440 site displayed severely
      reduced ADP-ribosylation activity (> 1000-fold). However, NAD glycohydrolase
      activity remained intact and in the case of ETAH440N actually increased 10-fold.
      NAD+ binding is not affected by substitutions at the 440 site as indicated by
      similar Km values for the ETA variants tested. Conformational integrity of the
      mutant toxins appears to be largely unaffected as assessed by analysis with a
      conformation-sensitive monoclonal antibody as well as sensitivity to proteinase
      digestion. In view of the location of His440 residue within or close to the
      proposed NAD(+)-binding site, these results suggest that His440 may be a
      catalytic residue involved in the transfer of the ADP-ribose moiety to the EF-2
      substrate.

PMID- 7822294
TI  - The sodium-calcium antiport of heart mitochondria is not electroneutral.
AB  - Heart mitochondria contain a nNa+/Ca2+ antiport that participates in the
      regulation of matrix [Ca2+]. Based largely on a single study (Brand, M. D. (1985)
      Biochem. J. 229, 161-166), there has been a consensus that this antiport promotes
      the electroneutral exchange of two Na+ for one Ca2+. However, a recent study in
      our laboratory (Baysal, K., Jung, D. W., Gunter, K. K., Gunter, T. P., and
      Brierley, G. P. (1994) Am. J. Physiol. 266, C800-C808) has shown that the Na(+)
      dependent efflux of Ca2+ from heart mitochondria has more energy available to it
      than can be supplied by a passive 2Na+/Ca2+ exchange. We have therefore re
      examined Brand's protocols using fluorescent probes to monitor matrix pH and free
      [Ca2+]. Respiring heart mitochondria, suspended in KCl and treated with ruthenium
      red to block Ca2+ influx, extrude Ca2+ and establish a large
      [Ca2+]out:[Ca2+]matrix gradient. The extrusion of Ca2+ under these conditions is
      Na(+)-dependent and diltiazem-sensitive and can be attributed to the nNa+/Ca2+
      antiport. Addition of nigericin increases the membrane potential (delta psi) and
      decreases delta pH to 0.1 or less, but has virtually no effect on the magnitude
      of the [Ca2+] gradient. Under these conditions a gradient maintained by
      electroneutral 2Na+/Ca2+ antiport should be abolished because the mitochondrial
      Na+/H+ antiport keeps the [Na+] gradient equivalent to the [H+] gradient. The
      [Ca2+] gradient is abolished, however, when an uncoupler is added to dissipate
      delta psi or when the exogenous electroneutral antiport BrA23187 is added. In
      addition, [Ca2+] influx via the nNa+/Ca2+ antiport in nonrespiring mitochondria
      is enhanced when delta psi is abolished. These results are consistent with Ca2+
      extrusion by an electrophoretic antiport that can respond to delta psi but not
      with an electroneutral antiport.

PMID- 7822296
TI  - Activation of acyl-coenzyme A:cholesterol acyltransferase by cholesterol or by
      oxysterol in a cell-free system.
AB  - Acyl-coenzyme A:cholesterol acyltransferase (ACAT) is an intracellular enzyme
      that catalyzes the conjugation of long chain fatty acid and cholesterol to form
      cholesteryl esters. It is an integral membrane protein located in the endoplasmic
      reticulum. Experiments performed in intact mammalian cells have shown that the
      rate of cholesteryl ester synthesis in intact cells, as well as the ACAT activity
      from cell extracts, are greatly activated by the addition of low density
      lipoprotein (LDL) or oxygenated sterols such as 25-hydroxycholesterol to the
      growth medium. However, the molecular mechanism(s) by which sterol(s) stimulate
      the ACAT activity remains to be elucidated. Recently, our laboratory reported the
      expression cloning of human ACAT cDNA (Chang, C. C. Y., Huh, H. Y., Cadigan, K.
      M., and Chang, T. Y. 1993) J. Biol. Chem. 268, 20747-20755). In the current
      study, we report the expression of human ACAT cDNA in insect Sf9 cells.
      Uninfected Sf9 cells do not express detectable ACAT-like activity. Infecting
      these cells with recombinant virus containing ACAT cDNA caused these cells to
      express high levels of ACAT protein and high levels of ACAT activity when assayed
      in vitro. The catalytic properties of ACAT expressed in these cells were found to
      be similar to those found in human tissue culture cells. The combination of high
      level of ACAT protein expression and the low level of cellular cholesterol
      content in the infected cells have provided us a novel opportunity to establish a
      simple cell-free system, whereby stimulation of ACAT by sterols can be readily
      demonstrated. Using this system, we have shown that cholesterol itself can serve
      as an ACAT activator in vitro, in addition to its role as an ACAT substrate. The
      current work provides the experimental basis to hypothesize that, inside
      mammalian cells, cholesterol itself may serve as a physiological regulator of
      ACAT.

PMID- 7822297
TI  - Structural recognition of a novel fibrinogen gamma chain sequence (117-133) by
      intercellular adhesion molecule-1 mediates leukocyte-endothelium interaction.
AB  - In addition to its role in hemostasis, fibrinogen is obligatorily required to
      mount competent inflammatory responses in vivo. A molecular prerequisite of
      fibrinogen-dependent inflammation may reside in its ability to associate with
      intercellular adhesion molecule-1 (ICAM-1), and enhance monocyte adhesion to
      endothelium by bridging the two cell types. Structure-function characterization
      of the novel ICAM-1 recognition of fibrinogen was carried out by synthetic
      peptidyl mimicry of the fibrinogen gamma chain. A novel peptide sequence, N117NQ
      KIVNLKEKVAQLEA133, designated gamma 3, dose-dependently inhibited (IC50
      approximately 20-40 micrograms/ml) binding of 125I-fibrinogen to endothelial
      cells or ICAM-1-expressing B lymphoblastoid Daudi cells. In contrast, none of the
      previously identified vascular cell fibrinogen interacting sequences was
      effective. Increasing concentrations of gamma 3 completely inhibited fibrinogen
      mediated adhesion of peripheral blood mononuclear cells or vitamin D3
      differentiated monocytic HL-60 cells to endothelium, but did not affect leukocyte
      endothelium interaction in the absence of fibrinogen. 125I-Labeled gamma 3 bound
      specifically and saturably to genetically engineered ICAM-1 transfectants, but
      not to control non-transfected cells, and associated with ICAM-1 on cytokine
      activated endothelium with a Kd of 34 microM. Consistent with functional
      recognition of ICAM-1, immobilized gamma 3 supported adhesion of JY lymphoblasts
      in a dose-dependent reaction inhibited by monoclonal antibodies to ICAM-1. We
      conclude that a novel fibrinogen gamma 3 sequence N117NQKIVNLKEKVAQLEA133 binds
      to ICAM-1 and modulates ICAM-1-dependent adhesion. These findings define the
      structural basis of fibrinogen:ICAM-1 recognition and provide a potential
      selective target for inhibiting fibrinogen-dependent inflammatory responses.

PMID- 7822298
TI  - Induction of ferritin synthesis by oxidative stress. Transcriptional and post
      transcriptional regulation by expansion of the "free" iron pool.
AB  - Ferritin, by regulating the "free" intracellular iron pool, controls iron
      catalyzed generation of reactive oxygen species, but its role in oxidative damage
      is still unclear. We show that ferritin synthesis is significantly stimulated in
      the liver of rats subjected to oxidative stress by treatment with phorone, a
      glutathione-depleting drug. RNA-bandshift assays document reduced activity of
      iron regulatory factor, in particular of IRFB, the cytoplasmic protein that post
      transcriptionally controls ferritin mRNA translation. Furthermore, Northern blot
      analysis shows increased accumulation of H and L subunit mRNAs, and nuclear run
      on experiments provide evidence of transcriptional activation. Direct
      measurements of intracellular free iron levels by EPR indicate that the increased
      ferritin synthesis can be mediated by an expansion of the free iron pool. An
      early drop of ferritin content after phorone treatment indicates that part of the
      iron that fuels the free pool might derive from ferritin degradation. Present
      data seem to suggest that, under conditions of oxidative stress, liver ferritin
      can represent either a pro- or an anti-oxidant in a time-dependent manner. In
      fact, its early degradation contributes to expand the intracellular free iron
      pool that, later on, activates multiple molecular mechanisms to reconstitute
      ferritin content, thus limiting the pro-oxidant challenge of iron.

PMID- 7822299
TI  - Regulation of the human C-reactive protein gene in transgenic mice.
AB  - Human C-reactive protein (hCRP) is a major acute-phase reactant in man. The
      regulation of the hCRP gene in transgenic mice is similar to that in humans. To
      map DNA regions required for the correct regulation of the hCRP gene, several
      constructs have been generated, and their expression in transgenic mice has been
      analyzed. Constructs lacking DNA regions surrounding the poly(A) site of the gene
      are not expressed either before or after induction in transgenic mice. Minimal
      regions 540 base pairs upstream and 1.2 kilobases downstream of the hCRP gene are
      sufficient for liver-specific expression. Extended 5'- and 3'-flanking regions
      are required to silence the expression prior to induction. Our findings
      demonstrate that regulatory sequences shown to confer inducible expression of the
      hCRP gene in hepatoma cell lines are insufficient in transgenic mice.

PMID- 7822300
TI  - Stimulation of protein phosphatase-1 activity by insulin in rat adipocytes.
      Evaluation of the role of mitogen-activated protein kinase pathway.
AB  - In this study, we examined the distribution of protein serine/threonine
      phosphatase-1 (PP-1) and analyzed the effect of insulin on PP-1 and its mechanism
      of activation in freshly isolated rat adipocytes. The adipocyte particulate
      fraction (PF) constituted approximately 80% of cellular PP-1 activity, while PP
      2A was entirely cytosolic. Insulin rapidly stimulated PF PP-1 in a time- and dose
      dependent manner (maximum stimulation at 5 min with 4 nM insulin).
      Immunoprecipitation of PF with an antibody against the site-1 sequence of rabbit
      skeletal muscle glycogen-associated PP-1 (PP-1G) subunit indicated that
      approximately 40% of adipocyte PP-1 activity was due to PP-1G form of the enzyme.
      Insulin stimulated PP-1G (120% over basal levels) without affecting the other
      forms of PP-1 in the PF. Insulin activation of PP-1 was accompanied by > 2-fold
      increase in the phosphorylation state of the 160-kDa regulatory subunit of PP-1.
      Stimulation of p21Ras/mitogen-activated protein kinase pathway (MAP) with GTP
      analogues also resulted in stimulation of PP-1 similar to insulin. The insulin
      effect on MAP kinase and PP-1 activation was blocked by a GTP antagonist, guanyl
      5'-yl thiophosphate. The inhibitors of MAP kinase activation (viz. cAMP agonists,
      SpcAMP and ML-9) also blocked PP-1 stimulation by insulin. The time course of MAP
      kinase activation preceded the phosphorylation of PP-1 regulatory subunit and PP
      1 activation. We conclude that insulin rapidly activates a membrane-associated PP
      1 in adipocytes, which may be similar to rabbit skeletal muscle PP-1G, and the
      activation is mediated by p21Ras/MAP kinase pathway.

PMID- 7822301
TI  - Identification of the protein 4.1 binding interface on glycophorin C and p55, a
      homologue of the Drosophila discs-large tumor suppressor protein.
AB  - Protein 4.1 is the prototype of a family of proteins that include ezrin, talin,
      brain tumor suppressor merlin, and tyrosine phosphatases. All members of the
      protein 4.1 superfamily share a highly conserved N-terminal 30-kDa domain whose
      biological function is poorly understood. It is believed that the attachment of
      the cytoskeleton to the membrane may be mediated via this 30-kDa domain, a
      function that requires formation of multiprotein complexes at the plasma
      membrane. In this investigation, synthetically tagged peptides and bacterially
      expressed proteins were used to map the protein 4.1 binding site on human
      erythroid glycophorin C, a transmembrane glycoprotein, and on human erythroid
      p55, a palmitoylated peripheral membrane phosphoprotein. The results show that
      the 30-kDa domain of protein 4.1 binds to a 12-amino acid segment within the
      cytoplasmic domain of glycophorin C and to a positively charged, 39-amino acid
      motif in p55. Sequences similar to this charged motif are conserved in other
      members of the p55 superfamily, including the Drosophila discs-large tumor
      suppressor protein. Our data provide new insights into how protein 4.1,
      glycophorin C, p55, and their non-erythroid homologues, interact with the
      cytoskeleton to exert their physiological effects.

PMID- 7822302
TI  - Arrestin interactions with G protein-coupled receptors. Direct binding studies of
      wild type and mutant arrestins with rhodopsin, beta 2-adrenergic, and m2
      muscarinic cholinergic receptors.
AB  - Arrestins play an important role in quenching signal transduction initiated by G
      protein-coupled receptors. To explore the specificity of arrestin-receptor
      interaction, we have characterized the ability of various wild-type arrestins to
      bind to rhodopsin, the beta 2-adrenergic receptor (beta 2AR), and the m2
      muscarinic cholinergic receptor (m2 mAChR). Visual arrestin was found to be the
      most selective arrestin since it discriminated best between the three different
      receptors tested (highest binding to rhodopsin) as well as between the
      phosphorylation and activation state of the receptor (> 10-fold higher binding to
      the phosphorylated light-activated form of rhodopsin compared to any other form
      of rhodopsin). While beta-arrestin and arrestin 3 were also found to
      preferentially bind to the phosphorylated activated form of a given receptor,
      they only modestly discriminated among the three receptors tested. To explore the
      structural characteristics important in arrestin function, we constructed a
      series of truncated and chimeric arrestins. Analysis of the binding
      characteristics of the various mutant arrestins suggests a common molecular
      mechanism involved in determining receptor binding selectivity. Structural
      elements that contribute to arrestin binding include: 1) a C-terminal acidic
      region that serves a regulatory role in controlling arrestin binding selectivity
      toward the phosphorylated and activated form of a receptor, without directly
      participating in receptor interaction; 2) a basic N-terminal domain that directly
      participates in receptor interaction and appears to serve a regulatory role via
      intramolecular interaction with the C-terminal acidic region; and 3) two
      centrally localized domains that are directly involved in determining receptor
      binding specificity and selectivity. A comparative structure-function model of
      all arrestins and a kinetic model of beta-arrestin and arrestin 3 interaction
      with receptors are proposed.

PMID- 7822303
TI  - Phosphatidylethanolamine is required for in vivo function of the membrane
      associated lactose permease of Escherichia coli.
AB  - Experiments with mutant Escherichia coli cells lacking phosphatidylethanolamine
      (PE) as a membrane component (DeChavigny, A., Heacock, P. N., and Dowhan, W.
      (1991) J. Biol. Chem. 266, 5323-5332) were carried out to establish whether or
      not PE is necessary for full function of the lac permease in vivo. The Vmax for
      active transport of both lactose (in cells lacking beta-galactosidase, lacZ) and
      the unhydrolyzable lactose analog, methyl-beta-D-galactopyranoside (TMG), by
      mutant cells lacking PE was reduced 5-10-fold relative to cells containing PE,
      while the Km for the uptake of both substrates was the same in both types of
      cells. The low rate of TMG and lactose uptake by PE-deficient cells was
      unaffected by the presence of a protonophore (uncoupler) and for TMG uptake was
      on the order of the greatly reduced rate of uptake in uncoupler-treated cells
      containing PE. The rate of entry of lactose into lacZ+ derivatives of both types
      of cells, as a measure of facilitated diffusion, was nearly the same. The Km for
      lactose (lacZ cells) and TMG transport in PE-deficient cells was unaffected by
      the presence of an uncoupler which had a small effect on Vmax. In PE-containing
      cells these kinetic parameters for TMG transport were reduced by an uncoupler to
      the level found with PE-deficient cells while an uncoupler reduced lactose uptake
      by PE-containing (lacZ) cells to below measureable levels. Inverted membrane
      vesicles made from both types of cells could be loaded with TMG, but energizing
      TMG-loaded vesicles by ATP only induced rapid, uphill, permease-dependent efflux
      of TMG from PE-containing vesicles. The decrease in apparent active transport
      activity of cells with no PE was not due to a change in membrane permeability, to
      a reduced delta microH+ (proton electrochemical gradient) across the cell
      membrane, or to a reduced level of membrane-associated lac permease protein.
      These results suggest that in the absence of PE the lac permease cannot couple
      substrate uptake to delta microH+ in order to effect accumulation of substrate
      and as a result only carries out facilitated diffusion.

PMID- 7822304
TI  - A kinetic analysis of the folding of human carbonic anhydrase II and its
      catalysis by cyclophilin.
AB  - The kinetics of unfolding and refolding of human carbonic anhydrase II (HCAII)
      and its catalysis by the peptidyl-prolyl-cis/trans-isomerase cyclophilin were
      investigated. HCAII contains 15 trans- and 2 cis-prolyl peptide bonds, and, when
      long-term denatured, virtually all unfolded molecules contain non-native prolyl
      isomers. In unfolding these molecules (Us) are produced slowly in a biphasic
      process reflecting the isomerization of several trans-prolines and of one cis
      proline. In refolding, the rapid formation of an intermediate of the molten
      globule type is followed by several slow prolyl isomerizations, which determine
      the rate of reactivation. By a short 10-s incubation in 5.0 M guanidinium
      chloride at 2 degrees C, unfolded HCAII species with all prolines still in the
      native conformation (Uf) could be produced. Surprisingly, only a fraction of Uf
      refolds rapidly, but the other molecules refold slowly. Evidently, some prolyl
      peptide bonds isomerize early in refolding, at the stage of the molten globule
      and as a consequence, molecules with incorrect prolyl isomers are formed in
      competition with the productive folding of Uf. This fraction of slow-folding
      molecules is strongly increased when cyclophilin is present, because it
      accelerates the formation of non-native prolyl isomers as long as the molecules
      remain in the molten globule state. Later cyclophilin catalyzes the isomerization
      of these prolyl peptide bonds toward the native state, which are stabilized in
      their conformation by further folding to the native state. This catalysis is very
      efficient, because only prolines that are accessible in the molten globule are
      involved in this sequence of isomerization and reisomerization.

PMID- 7822305
TI  - Enthalpy-entropy compensation in DNA melting thermodynamics.
AB  - We investigate enthalpy-entropy compensation for melting of nearest-neighbor
      doublets in DNA. Based on data for 10 normal doublets and for doublets containing
      a mispaired or analog base, the correlation of delta Szero with delta Hzero
      follows a rectangular hyperbola. Doublet melting temperature relates linearly to
      delta Hzero by Tm = T(o) + delta Hzero/a, where T(o) = 273 K and a = 80 cal/mol
      K. Thus Tm is proportional to delta Hzero + aTo rather than to delta Hzero alone
      as previously thought by assuming delta Szero to be constant. The term aTo = 21.8
      kcal/mol may reflect a constant enthalpy change in solvent accompanying the DNA
      enthalpy change for doublet melting and is roughly equivalent to breaking four H
      bonds between water molecules for each melted doublet. The solvent entropy change
      (aTo/Tm) declines with increasing Tm, while the DNA entropy change (delta
      Hzero/Tm) rises, so the combined DNA + solvent entropy change stays constant at
      80 cal/K/mol of doublet. If such constancy in DNA + solvent entropy changes also
      holds for enzyme clefts as "solvent," then free energy differences for competing
      correct and incorrect base pairs in polymerase clefts may be as large as enthalpy
      differences and possibly sufficient to account for DNA polymerase accuracy. The
      hyperbolic relationship between delta Szero and delta Hzero observed in 1 M salt
      can be used to evaluate delta Hzero and delta Szero from Tm at lower,
      physiologically relevant, salt concentrations.

PMID- 7822306
TI  - Interactions between the methylation sites of the Escherichia coli aspartate
      receptor mediated by the methyltransferase.
AB  - Mutations made at and near the methylation sites of the Escherichia coli
      aspartate receptor were found to affect the methylation rates of the remaining
      methylation sites. The results supported a model in which the methyltransferase
      enzyme contacts a residue seven amino acids to the C terminus of a site being
      methylated. The presence of a negatively charged residue at that position
      inhibits methylation, whereas a neutral residue has no effect. Methylation sites
      in the wild type receptor may also influence the methylation of other sites which
      are 7 residues away through a physical contact with the methyltransferase.

PMID- 7822308
TI  - GH3 pituitary tumor cells contain heteromeric type I and type II receptor
      complexes for transforming growth factor beta and activin-A.
AB  - Transforming growth factors beta (TGF-beta s) and activins induce and inhibins
      block secretion of follicle-stimulating hormone by rat GH3 pituitary tumor cells.
      Cheifetz et al. (Cheifetz, S., Ling, N., Guillemin, R., and Massague, J. (1988)
      J. Biol. Chem. 263, 17225-17228) reported that GH3 cells express a approximately
      50-kDa surface protein, termed the type IV TGF-beta receptor, that directly binds
      all of these peptide hormones. Here we show that GH3 cells express the previously
      identified type I and type II receptors for TGF-beta and activin-A.
      Immunoprecipitation of affinity-labeled surface binding proteins with antisera
      specific to known receptors demonstrated independent heteromeric complexes of TGF
      beta types I and II receptors and of activin types I and II receptors. As judged
      by ligand-binding and cross-linking analysis, TGF-beta binding to the TGF-beta
      receptors is not inhibited by activin-A and activin-A binding to its receptors is
      not inhibited by TGF-beta. Screening of a cDNA library from GH3 cells for
      potential receptor serine-threonine kinases yielded the known types I and II TGF
      beta and activin receptors. The presumed common intracellular signaling pathway
      for TGF-beta and activin in GH3 cells appears to be mediated by distinct cell
      surface receptors.

PMID- 7822307
TI  - A novel method to co-localize glycosaminoglycan-core oligosaccharide
      glycosyltransferases in rat liver Golgi. Co-localization of galactosyltransferase
      I with a sialyltransferase.
AB  - 4-Methylumbelliferyl-beta-xyloside (Xyl beta MU) primes glycosaminoglycan
      synthesis by first serving as an acceptor for the addition of 2 galactoses and 1
      glucuronic acid residue to make the typical core structure, GlcUA beta 1, 3Gal
      beta 1,3Gal beta 1,4Xyl beta MU. To investigate the relative localization of
      these biosynthetic enzymes, intact and properly oriented rat liver Golgi
      preparations were incubated with Xyl beta MU and 1 microM UDP-[3H]Gal and then
      chased with 5 microM of unlabeled UDP-Gal, UDP-GlcUA, UDP-GlcNAc, UDP-GalNAc, and
      CMP-Neu5Ac. Under these conditions, no intervesicular transport occurs and
      acceptor labeling depends entirely upon transporter-mediated delivery of the
      labeled sugar nucleotides into the lumen of a vesicle and co-localization of the
      appropriate glycosyltransferases. The labeled products were isolated from the
      incubation medium and from within the Golgi and their structures analyzed by C18,
      anion-exchange, and amine adsorption high performance liquid chromatography in
      combination with glycosidase digestions. Surprisingly, the major products within
      the Golgi were two sialylated xylosides (Sia alpha 2,3Gal beta 1,4Xyl-beta MU and
      Sia alpha 2,8Sia alpha 2,3Gal beta 1,4Xyl beta MU) rather than the expected group
      of partially completed GAG core structures. Less than 10% of the products within
      the Golgi are the expected core structures containing a second Gal residue or, in
      addition, GlcUA. The amount of the sialylated products is only partially
      decreased if the chase is omitted or if the chase is done in the absence of added
      CMP-Sia, suggesting a pool of previously transported CMP-Sia drives synthesis of
      the major products. Conversely, when detergent permeabilized vesicles are
      provided with high concentration of the same sugar nucleotides, the ratio of
      sialylated products is reduced and replaced by an increase in GAG-like products.
      These results argue that GAG core-specific Ga1 transferase I and II are not
      extensively co-localized within the same Golgi compartment. By contrast,
      glycosaminoglycan core Gal transferase I is substantially co-localized with an
      alpha-2,3-sialyltransferase and an alpha-2,8-sialyltransferase. Incubating intact
      Golgi vesicles with exogenous diffusible acceptors offers a novel method to
      assess the functional co-localization of glycosyltransferases of multiple
      pathways within the Golgi compartments.

PMID- 7822309
TI  - A rat pituitary tumor cell line (GH3) expresses type I and type II receptors and
      other cell surface binding protein(s) for transforming growth factor-beta.
AB  - A rat pituitary tumor cell line (GH3) has been reported to express transforming
      growth factor-beta (TGF-beta) binding components of 70-74 kDa (ligand included),
      denoted TGF-beta type IV receptor. We investigated whether the type IV receptor
      corresponds to any of the recently cloned type I receptors for proteins in the
      TGF-beta super-family. TGF-beta type I receptor (T beta R-I) complexes of 69-72
      kDa formed a heteromeric complex with T beta R-II in GH3 cells, as detected by
      immunoprecipitation. In addition, TGF-beta formed complexes of 72-74 kDa, which
      were different from T beta R-I and the other known type I receptors, and were not
      dependent on T beta R-II for binding. The GH3 cells were resistant to the growth
      inhibitory activity of TGF-beta, but a transcriptional response was activated by
      TGF-beta in this cell line, presumably through the T beta R-II and T beta R-I
      complex. These results indicate that GH3 cells have T beta R-I and T beta R-II
      and, in addition, other binding protein(s) which form 72-74-kDa complexes with
      TGF-beta; the function of the latter component(s) remains to be elucidated.

PMID- 7822310
TI  - Substitution of Asp for Asn at position 132 in the active site of TEM beta
      lactamase. Activity toward different substrates and effects of neighboring
      residues.
AB  - Using a random, combinatorial scheme of mutagenesis directed against the
      conserved SDN region of TEM beta-lactamase, and selective screening in ampicillin
      plates, we obtained the N132D mutant enzyme. The kinetic characterization of this
      mutant indicated relatively small effects compared to the wild-type. Both pK1 and
      pK2 for catalysis were decreased about 1 unit relative to the pK's for the wild
      type. This effect was predominantly due to changes in Km. In contrast to the wild
      type, the pH-rate profiles of the mutant showed that Km for several side chain
      containing penicillin substrates increases when the pH is above 5.5. 6
      Aminopenicillanic acid, which lacks a side chain, did not show this effect. With
      benzylpenicillin, ampicillin, and carbenicillin, kcat for the mutant showed a
      similar pH dependence as the wild type. With 6-aminopenicillanic acid, kcat for
      the mutant was greater than that for the wild type. The nature of the 104 side
      chain may affect the environment of Asp132; double mutants N132D/E104X (where X
      can be Q or N) are unable to confer antibiotic resistance to bacterial cells. The
      computed contact interactions from modeling substrate complexes between
      benzylpenicillin or 6-aminopenicillanic acid with the N132D mutant confirmed the
      importance of the protonation state of residue Asp132 for the complex stability
      with side chain-containing substrates. The data indicate that the contact between
      the side chain of residue 132 and the substrate is relevant for the ground state
      recognition, but because of close contact with several important groups in its
      neighborhood, residue 132 is also indirectly involved in the catalytic step of
      the wild-type enzyme.

PMID- 7822311
TI  - A new TEM beta-lactamase double mutant with broadened specificity reveals
      substrate-dependent functional interactions.
AB  - Using a random combinatorial mutagenesis of TEM beta-lactamase, directed against
      residues potentially involved in substrate discrimination, followed by selection
      on third generation cephalosporins, we obtained the double mutant E104M/G238S.
      Additionally, by using cloning strategies and site-directed mutagenesis we
      constructed the individual single mutants and also the single modification E104K
      and the double mutant E104K/G238S, which broaden the specificity of clinically
      isolated TEM beta-lactamase variants. The kinetic characterization of the
      purified double mutant E104M/G238S and its single counterparts E104M and G238S
      was carried out. The single mutant E104M exhibited increased kcat values against
      all substrates tested. Km values remained similar to the values shown by the wild
      type enzyme. The mutation at E104M was responsible for the increased hydrolysis
      rate against cefuroxime shown by the double mutant E104/G238S. The effect of
      mutation G238S varied more pronouncedly, depending on the substrate. In general,
      a lower Km was observed, but also a decreased kcat. The double mutant E104M/G238S
      exhibited a higher hydrolytic rate against cefotaxime compared with the
      corresponding single mutations. We observed nearly a 1000-fold greater kcat/Km
      for the double mutant than for the wild type. This improvement in catalysis was
      the consequence of increased kcat and decreased Km values. Computed contact
      interactions from modeling substrate complexes show reliable results only for
      benzylpenicillin. The modeling results with this substrate confirmed the observed
      enzyme activities for the different single and double mutants. Analysis of the
      apparent coupling energies, as calculated from the kinetic parameters of the
      single and double mutants, showed that the quantitative effect of a second
      mutation on a single mutant was either absent, additive, partially additive, or
      synergistic with respect to the first mutation, depending on the substrate
      analyzed.

PMID- 7822312
TI  - Epigenetic gene inactivation induced by a cis-acting methylation center.
AB  - In this report we test the hypothesis that a cis-acting methylation center can
      induce epigenetic gene inactivation. The cis-acting element used is an 838-base
      pair fragment that was shown previously to provide a de novo methylation signal
      (Mummaneni, P., Bishop, P. L., and Turker, M.S. (1993) J. Biol. Chem. 268, 552
      558). Its normal location is approximately 1.3 kilobase pairs upstream of the
      mouse aprt (adenine phosphoribosyltransferase) gene. To determine if the
      methylation center could induce inactivation of the aprt gene, a plasmid
      construct was created in which the methylation center was moved next to the aprt
      promoter. Transfection experiments demonstrated inactivation of the aprt gene on
      the hybrid construct. The inactivation event was shown with a Southern blot
      analysis to correlate with hypermethylation and to be reversible by treatment
      with 2-deoxy-5'-azacytidine, a demethylating agent. Interestingly, gene
      inactivation induced by the methylation center required truncation of the aprt
      promoter. The results demonstrate that epigenetic gene inactivation can be
      induced by a DNA methylation center.

PMID- 7822313
TI  - Binding of the pyruvate dehydrogenase kinase to recombinant constructs containing
      the inner lipoyl domain of the dihydrolipoyl acetyltransferase component.
AB  - The dihydrolipoyl acetyltransferase (E2) component of the mammalian pyruvate
      dehydrogenase complex forms a 60-subunit core in which E2's inner domain forms a
      dodecahedron shaped structure surrounded by its globular outer domains that are
      connected to each other and the inner domain by 2-3-kDa mobile hinge regions. Two
      of the outer domains are approximately 10 kDa lipoyl domains, an NH2-terminal
      one, E2L1, and, after the first hinge region a second one, E2L2. The pyruvate
      dehydrogenase kinase binds tightly to the lipoyl domain region of the oligomeric
      E2 core and phosphorylates and inactivates the pyruvate dehydrogenase (E1)
      component. We wished to determine whether lipoyl domain constructs prepared by
      recombinant techniques from a cDNA for human E2 could bind the bovine E1 kinase
      and, that being the case, to pursue which lipoyl domain the kinase binds. We also
      wished to gain insights into how a molecule of kinase tightly bound to the E2
      core can rapidly phosphorylate 20-30 molecules of the pyruvate dehydrogenase (E1)
      component which are also bound to an outer domain of the E2 core. We prepared
      recombinant constructs consisting of the entire lipoyl domain region or the
      individual lipoyl domains with or without the intervening hinge region.
      Constructs were made and used both as free lipoyl domains and fused to
      glutathione S-transferase (GST). Using GSH-Sepharose to selectively bind GST
      constructs, tightly bound kinase was shown to rapidly transfer in a highly
      preferential way from intact E2 core to GST constructs containing the E2L2 domain
      rather than to ones containing only the E2L1 domain. GST-E2L2-kinase complexes
      could be eluted from GSH-Sepharose with glutathione. Delipoylation of E2L2 by
      treatment with lipoamidase eliminated kinase binding supporting a direct role of
      the lipoyl prosthetic group in this association. Transfer to and selective
      binding of the kinase by E2L2 but not E2L1 was also demonstrated with free
      constructs using a sucrose gradient procedure to separate the large E2 core from
      the various lipoyl domain constructs. E2L2 but not E2L1 increased the activity of
      resolved kinase by up to 43%. We conclude that the kinase selectively binds to
      the inner lipoyl domain of E2 subunits and that this association involves its
      lipoyl prosthetic group. We further suggest that transfer of tightly bound kinase
      between E2L2 domains occurs by a direct interchange mechanism without formation
      of free kinase (model presented).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7822314
TI  - The C-terminal region of membrane type matrix metalloproteinase is a functional
      transmembrane domain required for pro-gelatinase A activation.
AB  - We identified a new matrix metalloproteinase (membrane type matrix
      metalloproteinase (MT-MMP)) that has a potential transmembrane (TM) domain at the
      C terminus and reported its expression on the surface of invasive tumor cells.
      The expression of MT-MMP induced specific activation of 72-kDa pro-gelatinase A
      (Sato, H., Takino, T., Okada, Y., Cao, J., Shinagawa, A., Yamamoto, E., and
      Seiki, M. (1994) Nature 370, 61-65). Thus, MT-MMP on the cell surface is thought
      to play an important role in various physiological and pathological processes
      accompanying tissue remodeling. In this study, we demonstrated that the potential
      TM domain deduced from the amino acid sequence functions as a membrane linker
      when it is fused to a secretory protein, tissue inhibitor of matrix
      metalloproteinases-1. The pro-gelatinase A activation function of MT-MMP was
      abolished by truncation of the TM domain and recovered by fusing the MT-MMP
      mutant with the TM domain of interleukin 2 receptor alpha-chain. The truncated MT
      MMP was released from the cells into the medium and detected as processed or
      modified forms. In spite of the deletion of the TM domain some portions of the
      mutant MT-MMP were still retained on the surface of cells. Thus, MT-MMP has an
      additional device to keep it on the cell surface. The TM domain however, plays an
      essential role in the pro-gelatinase A activation function of MT-MMP, probably
      regulating its fine orientation or the localization that is necessary to interact
      with substrate.

PMID- 7822315
TI  - Oscillations of reaction center II-D1 protein degradation in vivo induced by
      repetitive light flashes. Correlation between the level of RCII-QB- and protein
      degradation in low light.
AB  - The D1 protein subunit of the photochemical reaction center II (RCII) turns over
      rapidly in oxygenic photosynthetic organisms exposed to the light. At high photon
      flux densities (PFD), photoinactivation of RCII precedes the degradation of the
      D1 protein. We found that the apparent quantum yield for the D1 protein
      degradation in Chlamydomonas cells is severalfold higher at low PFDs (10-100
      mumol m-2 s-1) as compared to that observed at PFDs which induce
      photoinactivation of RCII (1.5-3 x 10(3) mumol m-2 s-1). Relative high levels of
      reduced RCII secondary plastoquinone acceptor, QB-, are induced in cells exposed
      to low PFDs as determined by thermoluminescence measurements. The probability of
      generating elevated levels of QB- which may recombine with the S2,3 oxidized
      states of the oxygen evolving complex decreases with increase in the light
      intensities at which consecutive double reduction of QB and exchange with the
      plastoquinone pool prevail. We have used light flashes to test if a correlation
      exists between the degradation of D1 protein and the relative level of QB-. D1
      protein degradation could be induced in dark-incubated cells exposed to a series
      of 1.4 x 10(3) single light flashes given at intervals compatible with generation
      of elevated levels of QB- and its decay by charge recombination. Oscillations of
      the QB- level in cells exposed to 960-1440 series of 1 to several flashes
      correlated with oscillations of the D1 protein degradation in Chlamydomonas cells
      and in the Scenedesmus wild type but not in the LF-1 mutant lacking photosystem
      II donor side activity. In this mutant the "S state cycle" and QB- oscillations
      are abolished. We propose that the process of recombination of long lived RCII-QB
      with the S2,3 states may involve damaging events related to the D1 protein
      degradation induced by light flashes or continuous low light in vivo.

PMID- 7822317
TI  - Proline-directed and non-proline-directed phosphorylation of PHF-tau.
AB  - To gain insight into the abnormal phosphorylation of PHF-tau, we have determined
      the phosphorylation sites by identifying phosphopeptides by means of ion spray
      mass spectrometry followed by sequencing of ethane-thiol-modified peptides.
      Nineteen sites have been identified; all but Ser-262 are localized to the amino-
      and carboxyl-terminal flanking regions of the microtubule-binding domain. Eleven
      sites correspond to fetal type sites. Unexpectedly, 10 are non-proline-directed,
      whereas the others are proline-directed. Thus, the abnormal phosphorylation of
      PHF-tau can be considered to consist of fetal type phosphorylation and additional
      proline-directed and non-proline-directed phosphorylation. This non-fetal type
      phosphorylation may provide PHF-tau with the unusual characteristics.

PMID- 7822316
TI  - Isolation of a protein target of the FKBP12-rapamycin complex in mammalian cells.
AB  - The immunosuppressive drug, rapamycin, interferes with an undefined signaling
      pathway required for the progression of G1-phase T-cells into S phase. Genetic
      analyses in yeast indicate that binding of rapamycin to its intracellular
      receptor, FKBP12, generates a toxic complex that inhibits cell growth in G1
      phase. These analyses implicated two related proteins, TOR1 and TOR2, as targets
      of the FKBP12-rapamycin complex in yeast. In this study, we have used a
      glutathione S-transferase (GST)-FKBP12-rapamycin affinity matrix to isolate
      putative mammalian targets of rapamycin (mTOR) from tissue extracts. In the
      presence of rapamycin, immobilized GST-FKBP12 specifically precipitates similar
      high molecular mass proteins from both rat brain and murine T-lymphoma cell
      extracts. Binding experiments performed with rapamycin-sensitive and -resistant
      mutant clones derived from the YAC-1 T-lymphoma cell line demonstrate that the
      GST-FKBP12-rapamycin complex recovers significantly lower amounts of the
      candidate mTOR from rapamycin-resistant cell lines. The latter results suggest
      that mTOR is a relevant target of rapamycin in these cells. Finally, we report
      the isolation of a full-length mTOR cDNA that encodes a direct ligand for the
      FKBP12-rapamycin complex. The deduced amino acid sequence of mTOR displays 42 and
      45% identity to those of yeast TOR1 and TOR2, respectively. These results
      strongly suggest that the FKBP12-rapamycin complex interacts with homologous
      ligands in yeast and mammalian cells and that the loss of mTOR function is
      directly related to the inhibitory effect of rapamycin on G1- to S-phase
      progression in T-lymphocytes and other sensitive cell types.

PMID- 7822318
TI  - Characterization of the scatter factor/hepatocyte growth factor gene promoter.
      Positive and negative regulatory elements direct gene expression to mesenchymal
      cells.
AB  - Scatter factor/hepatocyte growth factor (SF/HGF) and its receptor c-Met represent
      a paracrine signaling system involved in mesenchymal-epithelial interactions
      during development and during tumor progression. We have examined the promoters
      of the mouse and human SF/HGF genes by deletion mapping followed by CAT assays as
      well as by gel retardation and footprinting analysis. The promoter sequences are
      highly conserved (89.5% identity) up to position -453 from the major
      transcription start site but diverged considerably further upstream. Both
      promoters are active in mesenchymal but not epithelial cells thus reflecting the
      expression pattern of the SF/HGF gene in cells in vitro and in vivo. We have here
      identified two regulatory sequences in the SF/HGF promoter: a negative element at
      positions -239 to -258 and a positive element near the major transcription start
      site; specific deletions destroyed the activities of these elements. We were not
      able to localize elements on the SF/HGF promoter region that mediate the
      previously described effects of transforming growth factor beta, 12-O
      tetradecanoylphorbol-13-acetate, and coculture of epithelial cells on SF/HGF gene
      expression. This study represents a first step toward understanding the
      intricately regulated and cell type-specific expression of the paracrine acting
      SF/HGF.

PMID- 7822319
TI  - Nuclear factor kappa B functions as a negative regulator for the rat androgen
      receptor gene and NF-kappa B activity increases during the age-dependent
      desensitization of the liver.
AB  - Transcriptional regulation of the steroid hormone receptor genes plays a central
      role in temporal changes of target cell sensitivity during development,
      maturation, and aging. Sequence-specific DNA-protein interactions mediate these
      regulatory functions. Progressive 5' deletion of the rat androgen receptor (rAR)
      gene immediately beyond the -572 base pair (bp) region causes a marked increase
      in its promoter activity. DNase I footprinting with nuclear proteins revealed a
      protected area encompassing -574- to -554-bp positions that begins with a
      perfectly palindromic nuclear factor kappa B (NF-kappa B) motif. Electrophoretic
      mobility shift analyses (EMSA) showed that the decameric rAR NF-kappa B site at
      positions -574 to -565 cross-competes with the authentic kappa immunoglobulin
      light chain enhancer for specific protein binding. Supershift with specific
      antibodies to NF-kappa B subunits confirmed that the two retarded bands observed
      in the EMSA with the labeled rAR probe are due to p50/p65 and p50/p50 dimers of
      the NF-kappa B/Rel proteins. Fragments of rAR promoter with either deletion or
      point mutation of the NF-kappa B site are found to be about 2- to 3-fold more
      effective as compared to the wild type control in driving a heterologous reporter
      gene in cellulo. Thus, unlike most other known cases, NF-kappa B acts as a
      negative regulator for the rAR gene. The physiological relevance of this
      repressor function is evident from a 10-fold increase in the p50/p50 form of the
      NF-kappa B activity in the liver of aged rats exhibiting hepatic androgen
      desensitization. The newly identified repressor element is a rare example of a
      naturally occurring perfect palindromic binding motif for the NF-kappa B/Rel
      family of transcription factors. This repressor factor and the positively acting
      age-dependent factor, ADF, described earlier (Supakar, P. C., Song, C. S., Jung,
      M. H., Slomczynska, M. A., Kim, J.-M., Vellanoweth, R. L., Chatterjee, B. & Roy,
      A. K. (1993) J. Biol. Chem. 268, 26400-26408) function to coordinate the tissue
      specific down-regulation of the rAR gene during aging.

PMID- 7822320
TI  - Membrane topology of a cysteine-less mutant of human P-glycoprotein.
AB  - A human P-glycoprotein devoid of cysteine residues was constructed by site
      directed mutagenesis for studying its topology. The cDNA for human P-glycoprotein
      A52 in which codons for cysteines 137, 431, 717, 956, 1074, 1125, 1227, 1288, and
      1304 were changed to Ala, was transfected into NIH 3T3 cells and analyzed with
      respect to its ability to confer resistance to various drugs. The cysteine-less P
      glycoprotein-A52 retained the ability to confer resistance to vinblastine,
      colchicine, doxorubicin, and actinomycin D with only a small decrease in
      efficiency relative to wild-type enzyme. Cysteine residues were then reintroduced
      into predicted extracellular or cytoplasmic loops of the cysteine-less P
      glycoprotein-A52, and the topology of the protein was determined using membrane
      permeant and impermeant thiol-specific reagents. It was found that 8 of 15
      cysteine residues introduced into P-glycoprotein-A52 could be biotinylated, when
      cells expressing the mutant P-glycoprotein were incubated with membrane-permeant
      biotin maleimide. Biotinylation of a cysteine residue placed in predicted
      extracellular loops between transmembrane segment (TM) 5 and TM6, TM7 and TM8, or
      TM11 and TM12 was blocked by pretreatment of the cells with a membrane-impermeant
      maleimide, suggesting that these residues have an extracellular location. By
      contrast, biotinylation of cysteine residues located in the predicted cytoplasmic
      loops between TM2 and TM3, TM4 and TM5, TM8 and TM9, or TM10 and TM11 were not
      blocked by pretreatment with membrane impermeant maleimide, suggesting that these
      residues were in the cytoplasm. These results are consistent with the model of P
      glycoprotein, which predicts six transmembrane segments in each of the two
      homologous halves of the molecule.

PMID- 7822321
TI  - Inhibition of zona pellucida gene expression by antisense oligonucleotides
      injected into mouse oocytes.
AB  - During murine oogenesis, the zona pellucida proteins (ZP1, ZP2, and ZP3) are
      synthesized and secreted to form an extracellular matrix that surrounds the
      oocyte and mediates specific biological functions essential to mammalian
      fertilization and early development. To investigate the relationship among the
      zona proteins during zona matrix assembly, we have undertaken to inhibit de novo
      biosynthesis of specific zona proteins with antisense oligonucleotides
      complementary to the 5'-ends of ZP2 (nucleotide position 19-42) and ZP3
      (nucleotide 21-44) mRNAs. When injected into the cytoplasm of growing mouse
      oocytes, the antisense oligonucleotides targeted specific zona mRNAs for
      degradation, as confirmed by a RNase protection assay. Individual zona pellucida
      protein synthesis was followed by immunoprecipitation with ZP2- and ZP3-specific
      monoclonal antibodies. New zona protein synthesis from the targeted mRNA was
      abolished, but nontargeted zona protein continued to be synthesized.
      Interestingly, abolishment of either ZP2 or ZP3 protein synthesis prevented the
      incorporation of the other protein into the extracellular zona matrix. These
      results suggest that ZP2 and ZP3 proteins are independent of each other in their
      biosynthesis but are dependent upon each other for their incorporation into the
      zona pellucida matrix. This study provides an experimental system in which
      destruction of a targeted mRNA generates a transient loss-of-expression phenotype
      during mouse oocyte growth.

PMID- 7822322
TI  - Purification, characterization, and partial amino acid sequence of a G protein
      activated phospholipase C from squid photoreceptors.
AB  - Invertebrate visual transduction is thought to be initiated by photoactivation of
      rhodopsin and its subsequent interaction with a guanyl nucleotide-binding protein
      (G protein). The identities of the G protein and its target effector have
      remained elusive, although evidence suggests the involvement of a phospholipase C
      (PLC). We have identified a phosphatidylinositol-specific PLC from the cytosol of
      squid retina. The enzyme was purified to near-homogeneity by a combination of
      carboxymethyl-Sepharose and heparin-Sepharose chromatography. The purified PLC,
      identified as an approximately 140-kDa protein by sodium dodecyl sulfate
      polyacrylamide gels, hydrolyzed phosphatidylinositol 4,5-bisphosphate (PIP2) at a
      rate of 10-15 mumol/min/mg of protein with 1 microM Ca2+. The partial amino acid
      sequence of the protein showed homology with a PLC cloned from a Drosophila head
      library (PLC21) and lesser homology with Drosophila norpA protein and mammalian
      PLC beta isozymes. Reconstitution of purified squid PLC with an AlF(-)-activated
      44-kDa G protein alpha subunit extracted from squid photoreceptor membranes
      resulted in a significant increase in PIP2 hydrolysis over a range of Ca2+
      concentrations while reconstitution with mammalian Gt alpha or Gi 1 alpha was
      without effect. These results suggest that cephalopod phototransduction is
      mediated by G alpha-44 activation of a 140-kDa cytosolic PLC.

PMID- 7822323
TI  - Stimulation of Drosophila mitochondrial DNA polymerase by single-stranded DNA
      binding protein.
AB  - Mitochondrial DNA polymerase from Drosophila embryos has been characterized with
      regard to its mechanism of DNA synthesis in the presence of single-stranded DNA
      binding protein from Escherichia coli. The rate of DNA synthesis by DNA
      polymerase gamma was increased nearly 40-fold upon addition of single-stranded
      DNA-binding protein. Processivity of mitochondrial DNA polymerase was increased
      approximately 2-fold, while its intrinsic rate of nucleotide polymerization was
      unaffected. Primer extension analysis showed that the rate of initiation of DNA
      strand synthesis by DNA polymerase gamma was increased 25-fold in the presence of
      single-stranded DNA-binding protein. Our results indicate that the stimulation of
      Drosophila DNA polymerase gamma by single-stranded DNA-binding protein results
      primarily from an increased rate of primer recognition and binding. Concurrent
      achievement of maximal activity and processivity by mitochondrial DNA polymerase
      in the presence of binding protein suggests that DNA polymerase gamma, like other
      replicative DNA polymerases, associates with accessory factors in vivo to
      catalyze efficient and processive DNA synthesis.

PMID- 7822324
TI  - Studies on the metabolism of retinol and retinol-binding protein in transthyretin
      deficient mice produced by homologous recombination.
AB  - Tissue needs for retinoids are believed to be satisfied through the delivery in
      the circulation of retinol by its specific plasma transport protein, retinol
      binding protein (RBP), which circulates as a 1-to-1 protein complex with
      transthyretin (TTR). The binding of RBP to TTR is thought to prevent filtration
      of retinol-RBP in the kidney and to play a role in secretion of RBP from
      hepatocytes. Recently a strain of mice (TTR-) that totally lacks immunoreactive
      TTR was produced by targeted mutagenesis. We have explored the effects of TTR
      deficiency on retinol and RBP metabolism in this mutant strain. In pooled plasma
      from the TTR- mice retinol levels averaged 6% of those of wild type animals.
      Similarly, plasma RBP in the TTR- mice was found to be 5% of wild type levels.
      Hepatic retinol and retinyl ester levels were similar for mutant and wild type
      mice, suggesting that the mutation affects neither the uptake nor storage of
      dietary retinol. Levels of retinol and retinyl esters in testis, kidney, spleen,
      and eye cups from TTR- mice were normal. Plasma all-trans-retinoic acid levels
      for the TTR- mice were 2.3-fold higher than those of wild type (425 versus 190
      ng/dl). Kidney RBP levels were similar for the mutant and wild type mice and we
      were unable to detect intact RBP in urine from TTR- mice. Hepatic RBP levels in
      the TTR- mice were 60% higher than those of wild type mice (39.8 versus 25.0
      micrograms of RBP/g of tissue). These data may suggest that there is a partial
      blockage in RBP secretion from TTR- hepatocytes that leads to lessened plasma
      levels of retinol-RBP.

PMID- 7822325
TI  - Decreased profilaggrin expression in ichthyosis vulgaris is a result of
      selectively impaired posttranscriptional control.
AB  - Ichthyosis vulgaris is an autosomal dominant disorder of keratinization
      characterized by mild hyperkeratosis and reduced or absent keratohyalin granules
      in the epidermis. Profilaggrin, a major component of keratohyalin granules, is
      reduced or absent from the skin of individuals with ichthyosis vulgaris. In this
      report, we have further characterized the molecular basis of low profilaggrin
      expression, which occurs in this disease. In situ hybridization revealed little
      profilaggrin mRNA in ichthyosis vulgaris-affected epidermis. In keratinocytes
      cultured from the epidermis of affected individuals, the abundance of
      profilaggrin was reduced to less than 10% of normal controls, while the mRNA
      level was decreased to 30-60% of controls. Expression of K1 and loricrin, other
      markers of epidermal differentiation, were not affected. Nuclear run-on assays
      indicated that the decrease in mRNA levels was not caused by aberrant
      transcription. Nucleotide sequencing of 5'-upstream, 3'-non-coding, and flanking
      regions of the profilaggrin gene from ichthyosis vulgaris-affected individuals
      revealed only minor changes, probably due to genetic polymorphisms. Our results
      indicate that defective profilaggrin expression in ichthyosis vulgaris is a
      result of selectively impaired posttranscriptional control.

PMID- 7822326
TI  - Analysis of the binding site on intercellular adhesion molecule 3 for the
      leukocyte integrin lymphocyte function-associated antigen 1.
AB  - Intercellular adhesion molecule 3 (ICAM-3, CD50) is a member of the
      immunoglobulin superfamily and is a constitutively expressed ligand for the
      leukocyte integrin LFA-1 (CD11a/CD18). ICAM-3 is expressed at high levels by all
      resting leukocyte populations and antigen presenting cells and is a major ligand
      for LFA-1 in the resting immune system. ICAM-3 is a signal transducer and may
      play a key role in initiating immune responses. Mutant ICAM-3 Fc-chimeric
      proteins were quantitatively analyzed for their ability to bind COS cells
      expressing human LFA-1. The LFA-1-binding site on ICAM-3 is located in the N
      terminal 2 Ig domains. Domains 3-5 do not significantly contribute to adhesion.
      The binding site has been further resolved by rational targeting of 14 point
      mutations throughout domains 1 and 2, coupled with modeling studies. Within
      domain 1 a cluster of residues (Glu37, Leu66, Ser68, and Gln75), that are
      predicted to lie on the CC'FG face of the Ig fold, play a dominant role in LFA-1
      binding.

PMID- 7822327
TI  - Studies in transgenic mice reveal potential relationships between secretin
      producing cells and other endocrine cell types.
AB  - We have produced transgenic mice expressing fusion genes consisting of 1.6
      kilobase pairs of the secretin gene 5' flanking region to direct the expression
      of human growth hormone (hGH) or simian virus 40 large T antigen to secretin
      producing cells. Analysis of different mouse tissues for hGH transcripts revealed
      expression in each of the major secretin-producing tissues, namely the intestine
      and endocrine pancrease. Multiple label immunohistochemistry demonstrated that
      the transgene was correctly directed to secretin cells in the intestinal tract,
      including a previously unrecognized population of secretin cells in the colon of
      adult and developing mice. In the small intestine, subpopulations of hGH
      containing cells frequently coexpressed substance P, serotonin, and
      cholecystokinin, whereas in the colon, cells expressing hGH frequently
      coexpressed glucagon, peptide YY, or neurotensin. Transgenic mice expressing
      large T antigen in secretin cells developed poorly differentiated neuroendocrine
      tumors of the small intestine, well differentiated colonic tumors containing
      glucagon-expressing cells, and insulin-producing tumors in pancreas. These
      studies indicate that the major cis-regulatory sequences necessary for secretin
      expression in enteroendocrine cells and fetal islets are localized with 1.6
      kilobase pairs of the transcriptional start site. Coexpression of reporter
      transgenes with several gastrointestinal hormones suggests a potential
      relationships between secretin cells and other enteroendocrine cell types, as
      well as pancreatic beta cells.

PMID- 7822329
TI  - Involvement of the Ets family factor PU.1 in the activation of immunoglobulin
      promoters.
AB  - The B cell-specific expression of immunoglobulin (Ig) genes is controlled by the
      concerted action of variable (V) region promoters and intronic or 3' enhancers,
      all of which are active in a lymphoid-specific manner. A crucial highly conserved
      element of the V region promoters is the octamer site -ATTTGCAT-, which can be
      bound by ubiquitous (Oct-1) as well as B cell-specific (Oct-2) factors. Another
      less conserved element found in many Ig promoters is pyrimidine-rich and has been
      shown to be functionally important, in particular for those Ig promoters that
      have only an imperfect octamer site. In this study we have analyzed the factors
      binding specifically to the pyrimidine-rich motif of the V kappa 19 promoter, a
      light chain gene promoter with an imperfect octamer site. Using nuclear extracts
      prepared from B cells, we detected two sets of specific complexes in
      electrophoretic mobility shift experiments. One complex appears to be ubiquitous
      but enriched in lymphoid cells and represents the binding of a potentially novel
      factor with an apparent molecular mass of approximately 50 kDa. The other complex
      was found only with extracts from pre-B or B cells as well as from a macrophage
      cell line and appears to be caused by the binding of PU.1, a factor of the Ets
      family. We show that on this Ig promoter Oct factors (Oct-1 or Oct-2) and PU.1
      can bind concomitantly but without synergism. By transfection experiments in non
      B cells we demonstrate that PU.1 is indeed able to activate this promoter in
      concert with Oct-2. Furthermore, we show that PU.1 can bind with varying
      affinities to the pyrimidine-rich elements of several other Ig promoters. These
      data suggest a more general role for PU.1 or other members of the Ets family in
      the activation of Ig promoters.

PMID- 7822328
TI  - Purified horseshoe crab factor G. Reconstitution and characterization of the (1-
      >3)-beta-D-glucan-sensitive serine protease cascade.
AB  - Horseshoe crab hemocyte lysate responds to (1-->3)-beta-D-glucans, initiating an
      enzymatic cascade, which culuminates in clot formation. We have purified to
      homogeneity the serine protease zymogen factor G, which is directly activated by
      (1-->3)-beta-D-glucans and which initiates the hemolymph clotting cascade. Factor
      G is a heterodimeric protein composed of two noncovalently associated subunits
      alpha (72 kDa) and beta (37 kDa). In the presence of (1-->3)-beta-D-glucans such
      as curdlan and paramylon, factor G is autocatalytically activated to an active
      serine protease named factor G. This activation is accompanied by limited
      proteolysis of both subunits: the 72-kDa subunit alpha is cleaved to 55-kDa and
      17-kDa fragments, and the 37-kDa subunit beta is shortened to 34 kDa. Longer
      incubations with (1-->3)-beta-D-glucans result in cleavage of the 55-kDa fragment
      to 46 kDa and the 34-kDa fragment to 32 kDa, with concomitant loss of amidase
      activity. Reconstitution experiments using purified proteins participating in the
      hemolymph clotting cascade demonstrate that factor G is capable of activating
      proclotting enzyme directly, resulting in the conversion of coagulogen to
      coagulin gel. Thus, purified factor G is shown to be the primary initiator of the
      (1-->3)-beta-D-glucan-sensitive coagulation pathway in the horseshoe crab
      hemocyte lysate.

PMID- 7822330
TI  - Functional consequences of alterations to amino acids at the M5S5 boundary of the
      Ca(2+)-ATPase of sarcoplasmic reticulum. Mutation Tyr763-->Gly uncouples ATP
      hydrolysis from Ca2+ transport.
AB  - The roles of the hydrophobic side chains of residues Phe760, Ile761, Tyr763,
      Leu764, and Ile765 located at the M5S5 boundary of the Ca(2+)-ATPase of
      sarcoplasmic reticulum were analyzed by site-directed mutagenesis. Substitution
      of Tyr763 with glycine resulted in a new phenotypic variant of the Ca(2+)-ATPase
      that catalyzed a high rate of Ca(2+)-activated ATP hydrolysis without net
      accumulation of Ca2+ in the microsomal vesicles. The ATPase activity of the
      Tyr763-->Gly mutant displayed characteristics similar to the ATPase activity of
      the wild-type enzyme measured in the presence of calcium ionophore, and the
      mutant was able to form the ADP-insensitive phosphoenzyme intermediate. Mutants
      Phe760-->Gly, Ile761-->Gly, Leu764-->Gly, and Ile765-->Gly were able to
      accumulate Ca2+. In mutants Leu764-->Gly and Ile765-->Gly, the turnover rate was
      low due to inhibition of dephosphorylation of the ADP-insensitive phosphoenzyme
      intermediate. On the other hand, mutant Leu764-->Lys dephosphorylated rapidly.
      Mutants Phe760-->Gly and Leu764-->Lys displayed apparent Ca2+ affinities that
      were reduced two and three orders of magnitude, respectively, relative to that of
      the wild-type.

PMID- 7822331
TI  - Separation of transactivation and AP1 antagonism functions of retinoic acid
      receptor alpha.
AB  - Retinoic acid receptors (RARs) regulate gene expression either by directly
      binding to the RAR-responsive elements or by antagonizing the action of c-Jun/c
      Fos (AP1). AP1 is involved in the expression of metalloproteases, cytokines and
      other factors which play critical roles in the turnover of extracellular matrix,
      inflammation and hyperproliferation in diseases such as psoriasis, rheumatoid
      arthritis and in tumor metastases. We demonstrate here that synthetic retinoids
      inhibit 12-O-tetradecanoylphorbol-14-acetate-induced transcription from the
      stromelysin AP1 motif through RAR alpha, -beta, and -gamma. Interestingly, these
      diaryl acetylenic retinoids, which are potent agonists only for RAR beta and RAR
      gamma, but not for RAR alpha, in transactivation assays, are able to inhibit AP1
      dependent gene expression through RAR alpha. Thus these analogs can
      differentially affect the transactivation and AP1 antagonistic functions of RAR
      alpha. These results demonstrate that the transactivation and AP1 antagonistic
      functions are separable, and it should be possible to develop retinoids that are
      completely specific for AP1 antagonism through all RARs. Furthermore, using an
      RAR-selective ligand, we also demonstrate the separation of ligand binding and
      AP1 antagonism functions of RARs.

PMID- 7822332
TI  - Stage-specific isoforms of complex II (succinate-ubiquinone oxidoreductase) in
      mitochondria from the parasitic nematode, Ascaris suum.
AB  - Complex II from mitochondria of the adult parasitic nematode, Ascaris suum,
      exhibits high fumarate reductase activity and plays a key role in the anaerobic
      electron transport observed in these organelles. In contrast, mitochondria
      isolated from free living second stage larvae (L2) of A. suum show much lower
      fumarate reductase activity than those from adults, whereas succinate
      dehydrogenase activities of mitochondria in both stages are comparable. In the
      present study, biochemical and antigenic properties of the partially purified
      enzymes from both larval and adult mitochondria were compared. Larval complex II
      eluted from the DEAE-Cellulofine column chromatography at a lower salt
      concentration than adult enzyme, whereas the apparent molecular size of both
      enzyme complexes estimated by gel permeation column chromatography was the same.
      The fumarate reductase activity of larval complex II was less than 3% of that of
      adult enzyme, and the Km values for substrates were significantly different
      between the two complexes. The flavoprotein subunit of larval complex II could be
      distinguished from that of adult complex II by two-dimensional gel
      electrophoresis and peptide mapping. The antibody against the smallest subunit
      (small subunit of cytochrome b558) of the adult enzyme did not cross-react with
      that of the larval enzyme. These results suggest that larval complex II differs
      from adult enzyme and is more similar to aerobic mammalian enzymes with low
      fumarate reductase activity. This is the first direct indication of the two
      different stage-specific forms of mitochondrial complex II.

PMID- 7822333
TI  - Transcriptional regulation of the intercellular adhesion molecule-1 gene by
      inflammatory cytokines in human endothelial cells. Essential roles of a variant
      NF-kappa B site and p65 homodimers.
AB  - Intercellular adhesion molecule-1 (ICAM-1) is greatly up-regulated on endothelial
      cells at sites of inflammation and is involved in leukocyte attachment and
      extravasation. Previously, we had shown that the ICAM-1 gene expression in human
      umbilical vein endothelial cells (HUVECs) was transcriptionally regulated by
      tumor necrosis factor-alpha (TNF-alpha) (Wertheimer, S. J., Myers, C. L.,
      Wallace, R. W., and Parks, T. P. (1992) J. Biol. Chem. 267, 12030-12035). In the
      present investigation, TNF-alpha-induced transcription was found to be initiated
      exclusively at two sites, 40 and 41 base pairs upstream of the translation start
      site. Deletion analysis of the 5' regulatory region of the ICAM-1 gene revealed a
      92-base pair sequence which was both necessary and sufficient to confer TNF-alpha
      responsiveness to a linked luciferase reporter gene in transient transfection
      assays. This TNF-alpha-responsive region contained a variant NF-kappa B site at 
      187 to -178, which when mutated, completely abolished ICAM-1 promoter activation
      by TNF-alpha, interleukin-1 beta, and lipopolysaccharide. Two inducible nuclear
      protein complexes bound to the ICAM-1 kappa B and were identified as the NF-kappa
      B p65 homodimer and p65/p50 heterodimer. Overexpression of p65, but not p50,
      transactivated the ICAM-1 promoter in a kappa B site-dependent manner in HUVECs.
      In addition, p65-mediated transactivation was suppressed by co-expression of p50.
      Our results suggest that cytokine activation of the ICAM-1 promoter in HUVECs may
      critically depend on p65 homodimers binding to a variant kappa B site.

PMID- 7822334
TI  - F2(Pmp)2-TAM zeta 3, a novel competitive inhibitor of the binding of ZAP-70 to
      the T cell antigen receptor, blocks early T cell signaling.
AB  - Signaling by the T cell antigen receptor (TCR) is mediated by 17-residue tyrosine
      based activation motifs (TAM) present in the cytoplasmic tails of the TCR zeta
      and CD3 chains. TAMs become tyrosine-phosphorylated upon TCR stimulation,
      creating a high affinity binding site for the tandem SH2 domains of ZAP-70. In
      permeabilized T cells, the association of TCR and ZAP-70 was inhibited by a
      protein tyrosine phosphatase (PTPase)-resistant TAM peptide analog, in which
      difluorophosphonomethyl phenylalanyl (F2Pmp) residues replaced phosphotyrosine.
      Inhibition of this association prevented TCR-stimulated tyrosine phosphorylation
      of ZAP-70 and reduced ZAP-70 kinase activity to basal levels. The reduction in
      ZAP-70 activity coincided with reduced tyrosine phosphorylation of a number of
      substrates. Such PTPase-resistant peptides, capable of disrupting SH2 domain
      mediated protein-protein interactions, should prove useful in further dissection
      of multiple signaling pathways and may serve as models for rationally designed
      chemotherapeutic agents for the treatment of autoimmune and neoplastic disorders.

PMID- 7822335
TI  - DNA polymerase beta conducts the gap-filling step in uracil-initiated base
      excision repair in a bovine testis nuclear extract.
AB  - The G:U mismatch in genomic DNA mainly arises from deamination of cytosine
      residues and is repaired by the base excision repair pathway. We found that a
      bovine testis crude nuclear extract conducts uracil-initiated base excision
      repair in vitro. A 51-base pair synthetic DNA substrate containing a single G:U
      mismatch was used, and incorporation of dCMP during repair was exclusively to
      replace uracil. A neutralizing polyclonal antibody against DNA polymerase beta
      (beta-pol) inhibited the repair reaction. ddCTP also inhibited the repair
      reaction, whereas aphidicolin had no significant effect, suggesting that activity
      of beta-pol was required. Next, the base excision repair system was reconstituted
      using partially purified components. Several of the enzymatic activities required
      were resolved, such that DNA ligase and the uracil-DNA
      glycosylase/apurinic/apyrimidinic endonuclease activities were separated from the
      DNA polymerase requirement. We found that purified beta-pol could restore full
      DNA repair activity to the DNA polymerase-depleted fraction, whereas purified DNA
      polymerases alpha, delta, and epsilon could not. These results with purified
      proteins corroborated results obtained with the crude extract and indicate that
      beta-pol is responsible for the single-nucleotide gap filling reaction involved
      in this in vitro base excision repair system.

PMID- 7822337
TI  - Both interleukin 4 and interleukin 13 induce tyrosine phosphorylation of the 140
      kDa subunit of the interleukin 4 receptor.
AB  - We have investigated tyrosine phosphorylation of cellular proteins induced by
      interleukin (IL) 4 and compared it with the effects of three related cytokines,
      IL-2, IL-7, and IL-13. We show here that both IL-4 and IL-13 stimulate tyrosine
      phosphorylation of the 140-kDa IL-4 receptor subunit, which suggests that this
      receptor protein is used by both cytokines. Receptor phosphorylation induced by
      IL-13 was both weaker and slower than with IL-4. Stimulation of cells with IL-2
      and IL-7 induced identical phosphorylation patterns to each other but not
      phosphorylation of the 140-kDa IL-4 receptor subunit. The only signal appearing
      upon stimulation with any of the four cytokines was the weak phosphorylation of
      an unidentified protein of 160 kDa. SH2 domains of p56lck and p59fyn precipitated
      the same proteins as anti-phosphotyrosine antibodies after IL-4 stimulation,
      which suggests that a src-type kinase may be involved in signal transduction
      through the IL-4 receptor.

PMID- 7822336
TI  - Multiple forms of mouse PG-M, a large chondroitin sulfate proteoglycan generated
      by alternative splicing.
AB  - We have isolated and sequenced cDNA clones that encode the core protein of PG-M
      like proteoglycan produced by cultured mouse aortic endothelial cells (Morita,
      H., Takeuchi, T., Suzuki, S., Maeda, K., Yamada, K., Eguchi, G., and Kimata, K.
      (1990) Biochem. J. 265, 61-68). A homology search of the cDNA sequence has
      suggested that the core protein is a mouse equivalent of chick PG-M(V1), one of
      the alternatively spliced forms of the PG-M core protein, which may correspond to
      human versican. Northern blot analysis revealed three mRNA species of 10, 9, and
      8 kilobases (kb) in size. The analysis of PG-M mRNA species in embryonic limb
      buds and adult brain revealed the presence of other mRNA species with different
      sizes; the one with the largest size (12 kb) was found in embryonic limb buds,
      and the ones with smaller sizes of 7.5 and 6.5 kb were in adult brain. Sequencing
      of cDNA clones for the smaller forms in the adult brain showed that they were
      different from PG-M(V1) in encoding the second chondroitin sulfate attachment
      domain (CS alpha) alone. Occurrence of the PCR products striding over the
      junction of the first and second chondroitin sulfate attachment domains suggested
      that a mRNA of 12 kb in size corresponded to a transcript without the alternative
      splicing (PG-M(V0)). It is likely, therefore, that multiforms of the PG-M core
      protein may be generated by alternative usage of either or both of the two
      different chondroitin sulfate attachment domains (alpha and beta) and that
      molecular forms of PG-M may vary from tissue to tissue by such an alternative
      splicing.

PMID- 7822338
TI  - Structure-function relationships in human interleukin-11. Identification of
      regions involved in activity by chemical modification and site-directed
      mutagenesis.
AB  - Chemical modification approaches combined with site-directed and deletion
      mutagenesis have been used to identify functionally critical regions/residues of
      recombinant human IL-11 (rhIL-11). Incubation of rhIL-11 with iodoacetic acid
      results in specific alkylation of a single methionine residue, Met58, and a 25
      fold reduction of in vitro biological activity on mouse plasmacytoma cells. A
      similar decrease in activity is observed when Met58 is substituted with Ala, Leu,
      Gln, Glu, or Lys by site-directed mutagenesis. Treatment of rhIL-11 with succinic
      anhydride leads to modification of the amino-terminal amino group and partial
      labeling of 2 lysines, Lys41 and Lys98, and to a 3-fold decrease in activity. The
      activity losses can be attributed to modification of the lysine residues, since
      the succinyl derivative of the amino terminus is fully active. In addition,
      carboxyl-terminal deletion mutagenesis studies have demonstrated that removal of
      the last 4 residues reduces rhIL-11 activity 25-fold, whereas removal of 8 or
      more amino acids results in an inactive molecule. Based on secondary structure
      predictions and the location of exon/intron boundaries in the IL-11 genomic
      structure, we propose a four-helix bundle topology as a structural model for rhIL
      11. This model has been tested by limited proteolysis using three side chain
      specific endoproteinases. A limited number of protease-sensitive cleavage sites
      are present in rhIL-11, and all but two are located in the postulated helix
      interconnecting loops or at helix termini. alpha-Helices, which in the proposed
      structure form a compact core of the molecule, are inaccessible to digestion
      under limiting conditions. According to the model, Met58, Lys41 and Lys98 are
      located on the surface of the molecule, in agreement with their preferential
      accessibility to chemical modifications. By analogy with human growth hormone, we
      postulate that Met58 and the carboxyl terminus of rhIL-11 are involved in the
      primary receptor binding site (site I), whereas Lys41 and Lys98 may be a part of
      binding site II.

PMID- 7822339
TI  - Horseshoe crab (1,3)-beta-D-glucan-sensitive coagulation factor G. A serine
      protease zymogen heterodimer with similarities to beta-glucan-binding proteins.

PMID- 7822340
TI  - The expression of platelet-derived growth-factor gene in Dupuytren contracture.
AB  - Dupuytren contracture is a disease of the palmar fascia characterized by nodular
      fibroblastic proliferation; its etiology and pathogenesis are poorly understood.
      Growth factors are polypeptides that regulate cell growth and differentiation and
      extracellular matrix production. Platelet-derived growth factor is known to cause
      fibroblastic proliferation, and it may be involved in the pathogenesis of
      Dupuytren contracture. The purpose of this study was to determine if the gene for
      the B chain of platelet-derived growth factor is expressed in Dupuytren
      contracture. Tissue from patients who had Dupuytren disease was examined
      immunohistochemically with the 5B5 antibody, which is a marker for fibroblasts.
      Polymerase chain reaction, gel electrophoresis, Southern blotting, and in situ
      hybridization were also used to study gene expression in the tissue as well as in
      normal fascia, A172 cells, and MRC5 cells. Total cellular RNA was extracted from
      tissue and cells. Polymerase chain reaction was done with oligonucleotide primers
      complementary to a portion of the platelet-derived growth-factor-B and platelet
      derived growth-factor-receptor genes. The platelet-derived growth-factor-B gene
      was expressed in all six specimens from the patients who had Dupuytren
      contracture as well as in the A172 cells, but not in the normal fascia lata or
      the MRC5 cells. These results were confirmed with Southern blotting of the
      products of the reaction with a platelet-derived growth-factor-B probe. The gene
      for the platelet-derived growth-factor receptor was expressed by all tissues and
      cells studied.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7822341
TI  - Abnormal findings on magnetic resonance images of asymptomatic shoulders.
AB  - Magnetic resonance images of the shoulders of ninety-six asymptomatic individuals
      were evaluated to determine the prevalence of findings consistent with a tear of
      the rotator cuff. The scans were reviewed independently by two diagnostic
      radiologists who are experienced in the interpretation of magnetic resonance
      images of the shoulder. The over-all prevalence of tears of the rotator cuff in
      all age-groups was 34 per cent (thirty-three). There were fourteen full-thickness
      tears (15 per cent) and nineteen partial-thickness tears (20 per cent). The
      frequency of full-thickness and partial-thickness tears increased significantly
      with age (p < 0.001 and 0.05, respectively). Twenty-five (54 per cent) of the
      forty-six individuals who were more than sixty years old had a tear of the
      rotator cuff: thirteen (28 per cent) had a full-thickness tear and twelve (26 per
      cent) had a partial-thickness tear. Of the twenty-five individuals who were forty
      to sixty years old, one (4 per cent) had a full-thickness tear and six (24 per
      cent) had a partial-thickness tear. Of the twenty-five individuals who were
      nineteen to thirty-nine years old, none had a full-thickness tear and one (4 per
      cent) had a partial-thickness tear. Magnetic resonance imaging identified a high
      prevalence of tears of the rotator cuff in asymptomatic individuals. These tears
      were increasingly frequent with advancing age and were compatible with normal,
      painless, functional activity. The results of the present study emphasize the
      potential hazards of the use of magnetic resonance imaging scans alone as a basis
      for the determination of operative intervention in the absence of associated
      clinical findings.

PMID- 7822342
TI  - Fracture of the acetabulum during insertion of an oversized hemispherical
      component.
AB  - A hemispherical metal-backed acetabular component that was oversized by two or
      four millimeters was introduced without cement into thirty fresh or embalmed
      cadaveric acetabula that were fifty, fifty-two, fifty-four, fifty-six, or fifty
      eight millimeters in diameter. Manual tapping was used to insert the component
      into ten fresh and ten embalmed specimens, and a materials testing machine was
      used for the remaining five fresh and five embalmed specimens. The magnitude of
      force and the number of pulses necessary to seat the component were determined
      for the insertions performed with the materials testing machine; 2000 and 3000
      newtons of force were required to insert the cups that were oversized by two and
      four millimeters, respectively. Visual and radiographic assessments were used to
      identify any resulting acetabular fractures. Over-all, eighteen (60 per cent) of
      the thirty acetabular specimens fractured. Of the eighteen fractures, only
      fifteen were detectable radiographically: ten on en face or lateral radiographs
      of the cup and five only on oblique radiographs of the cup. The remaining three
      fractures were apparent only after the removal of the acetabular
      component.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7822343
TI  - The effect of the medial collar in total hip arthroplasty with porous-coated
      components inserted without cement. An in vivo canine study.
AB  - We performed an in vivo study in a canine model to compare the results of the use
      of a porous-coated collared femoral component with those of the use of a porous
      coated collarless femoral component in total hip arthroplasties without cement.
      Our study focused on the comparative proximal strain pattern, bone ingrowth, and
      cortical porosity of the two types of prostheses. We used a trochanteric wire
      marker to measure subsidence. The use of the limb was assessed with gait
      analysis. Twelve weeks after the operation, the collarless components had
      significantly greater bone ingrowth proximally (p = 0.003) and were associated
      with significantly lower cortical porosity (p = 0.006). There were no differences
      between the groups with regard to either axial or hoop strain. While the group
      that had a collarless prosthesis had significantly less proximal-medial
      radiolucency (p = 0.03), there were no differences between the groups with regard
      to subsidence.

PMID- 7822344
TI  - Bilateral non-union of the carpal scaphoid in a child. A case report.

PMID- 7822345
TI  - Successful operative treatment of a displaced subcapital fracture of the hip in
      transient osteoporosis of pregnancy. A case report and review of the literature.

PMID- 7822346
TI  - Proliferative myositis in a child. A case report.

PMID- 7822347
TI  - Tuberculous arthritis of the sternoclavicular joint. A report of three cases.

PMID- 7822348
TI  - Glomus tumor in the patellar ligament. A case report.

PMID- 7822349
TI  - Fractures about the ankle.

PMID- 7822350
TI  - Determination of acetabular coverage of the femoral head with use of a single
      anteroposterior radiograph.

PMID- 7822351
TI  - Cathepsin G and alpha 1-antichymotrypsin in the local host reaction to loosening
      of total hip prostheses.
AB  - The tissue localization and content of the proteolytic enzyme cathepsin G and its
      inhibitor alpha 1-antichymotrypsin were studied in the local host reaction to
      loosening of total hip-replacement prostheses in eleven patients and were
      compared with those in samples of non-inflammatory tissue from the synovial
      capsule obtained during arthroscopies of the knee. Immunostaining demonstrated
      cellular localization of cathepsin G in 71 per cent of monocyte or macrophage
      like cells and in 46 per cent of fibroblast-like cells in the samples of
      interface tissue between the bone and the loose acetabular component obtained at
      the time of the total hip replacements, and in 59 and 42 per cent, respectively,
      in the samples of pseudocapsular tissue obtained at the same time, whereas the
      synovial lining cells in the samples of non-inflammatory tissue from the synovial
      capsule revealed only a slight immunoreactivity to cathepsin G. Cathepsin-G
      activity was also measured with synthetic succinyl-alanine-alanine-proline
      phenylalanine-paranitroanilide as a substrate, the degradation of which was
      monitored spectrophotometrically. In accordance with results from
      immunohistochemical studies, cathepsin-G activity was found in the samples of
      interface tissue (31.6 international units per liter) and the samples of
      pseudocapsular tissue (15.5 international units per liter) obtained during the
      total hip replacements, whereas the level of cathepsin-G was low in the samples
      of non-inflammatory synovial capsular tissue (2.5 international units per liter).
      Cathepsin-G activity in the samples of pseudosynovial fluid obtained at the time
      of the total hip replacements was low (2.4 international units per liter),
      although immunoblot analysis showed marked immunoreactive cathepsin G in the
      samples of pseudosynovial fluid. This low activity of cathepsin G might be
      explained by the presence of alpha 1-antichymotrypsin, which was detected by
      laser nephlometric immunoassay and immunoblot analysis. These results demonstrate
      increased concentration of cathepsin G locally in the tissues around loose total
      hip-replacement prostheses. Because cathepsin G is not only able to act on
      extracellular matrix components (such as gelatin, proteoglycan, elastin, and
      laminin) at a physiological pH but also is able to activate collagenase,
      gelatinase, and stromelysin proenzymes, to inactivate tissue inhibitor of
      metalloproteinases, and to modulate tumor necrosis factor-alpha, it may play an
      important role in the degradation of periprosthetic connective tissue and in the
      lysis of bone around the implant, thus contributing to the loosening of
      prostheses.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7822352
TI  - Ingrowth of blood vessels in disc degeneration. Angiographic and histological
      studies of cadaveric spines.
AB  - Angiograms were made of twenty-two cadaveric lumbar spines to determine the
      presence of any new blood vessels between adjacent lumbar vertebrae and
      corresponding discs. The annulus and adjacent longitudinal ligaments were also
      analyzed histologically. A total of 105 intervertebral spaces were studied. It
      was found that the normal anastomosing arteries in the posterior longitudinal
      ligament were significantly obliterated with advancing degeneration of the disc
      (p < 0.001), whereas several tiny tortuous arteries--often running between the
      osteophytic spurs--were seen in the anterolateral aspects of the intervertebral
      spaces connecting the adjacent vertebrae. Histological examination of the
      anterolateral part of the annulus showed that the vascularity of the annulus
      increased significantly with degeneration of the disc (p < 0.001), and most of
      the arteries had a vertical orientation. Regression analysis showed that vascular
      changes occurred before degeneration of the disc at every lumbar level,
      suggesting that disturbances in the nutritional supply may precede degeneration.
      The correlation coefficient was 0.77 (95 per cent confidence limit, 0.52 to 0.90)
      for the increase in annular vascularity with an increase in the age of the
      individual at the time of death and 0.86 (95 per cent confidence limit, 0.69 to
      0.94) for the increase in degeneration of the disc with an increase in age.

PMID- 7822353
TI  - Lumbar foraminal stenosis: critical heights of the intervertebral discs and
      foramina. A cryomicrotome study in cadavera.
AB  - One hundred lumbar intervertebral foramina from eighteen spines of fresh cadavera
      were studied to assess the relationship between compression of the nerve root and
      the height of the intervertebral disc and the morphological characteristics of
      the intervertebral foramen as determined on cryomicrotome sections. The critical
      posterior disc height and the critical foraminal height that were associated with
      entrapment and compression of the nerve root were determined. Significant
      positive correlations were demonstrated between compression of the nerve root and
      the posterior disc height, the foraminal height, and the foraminal cross
      sectional area for the four intervertebral levels between the second lumbar and
      first sacral vertebrae. Nerve-root compression was evident in twenty-one of the
      100 foramina, in eight of the ten foramina in which the posterior disc height was
      four millimeters or less, and in four of the five foramina in which the foraminal
      height was fifteen millimeters or less. These critical dimensions may be
      indicators of foraminal stenosis in the lumbar spine. However, compression of a
      spinal nerve root does not always cause sciatica, and the clinical findings must
      always be taken into account when a diagnosis of stenosis is considered.

PMID- 7822354
TI  - Posterior arthrodesis and instrumentation in the immature (Risser-grade-0) spine
      in idiopathic scoliosis.
AB  - We performed a retrospective study of the long-term results of posterior
      instrumentation and arthrodesis of the spine in forty-three patients who had
      idiopathic scoliosis and a Risser grade of 0 at the time of the operation. The
      average age of the patients was 12.4 years (range, 6.7 to 15.5 years) at the time
      of the operation. The triradiate cartilages were open in twenty-three patients
      and closed in twenty. At the time of the latest follow-up evaluation (average
      duration of follow-up, four years; range, two to eleven years), seventeen
      patients had a Risser grade of 5; twenty-two, 4; two, 3; one, 2; and one, 0. The
      crankshaft phenomenon, a progressive deformity resulting from continued growth of
      the anterior aspect of the spine after posterior arthrodesis, was seen in only
      one patient who had closed triradiate cartilages and in ten patients who had open
      triradiate cartilages (p = 0.004). The most common radiographic finding was a
      progressive rib-vertebra angle difference, which increased more than 10 degrees
      in seven of the eleven patients who had the crankshaft phenomenon. The mean
      increase in these eleven patients was 22 degrees, compared with no increase in
      the thirty-two other patients (p < 0.0001). Open triradiate cartilages (r = 0.58,
      p = 0.0001) and a younger age at the time of the operation (p < 0.0001) were
      predictive of the amount of progression as a result of the crankshaft phenomenon.
      In patients who had open triradiate cartilages, less skeletal maturity was also
      predictive of progression as a result of the crankshaft phenomenon (r = -0.72, p
      = 0.0002).

PMID- 7822355
TI  - Childhood scoliosis: clinical indications for magnetic resonance imaging.
AB  - We retrospectively reviewed the magnetic resonance imaging studies that had been
      made for ninety-five patients who had idiopathic scoliosis. We wished to
      determine if we could identify any criteria that should be met before these
      studies are performed. The study group included thirty-one male patients and
      sixty-four female patients. The average age at the time of the imaging study was
      thirteen years (range, one to twenty-eight years). The average curve was 41
      degrees (range, 11 to 95 degrees). Fourteen patients were seen to have an
      intraspinal abnormality on the imaging study: twelve had a syrinx, one had a
      syrinx and an astrocytoma of the spinal cord, and one had dural ectasia. Five of
      the eight patients who were less than eleven years old and who had a left
      thoracic curve had an intraspinal abnormality on the imaging study, but this
      combination of factors did not indicate the need for operative intervention. Four
      of the intraspinal abnormalities in the fourteen patients necessitated
      neurosurgical intervention; if the criteria for obtaining the imaging study had
      been restricted to neck pain and headache--particularly with exertion--and
      neurological findings such as ataxia, weakness, and a cavus foot, these
      abnormalities would have been diagnosed.

PMID- 7822356
TI  - Massive allografts in the treatment of osteosarcoma and Ewing sarcoma in children
      and adolescents.
AB  - A retrospective review was performed of the results of all allograft
      reconstructions that had been done after the resection of an osteosarcoma or an
      Ewing sarcoma in a skeletally immature patient between 1982 and 1989 at The
      Hospital for Sick Children in Toronto. There were twenty-six patients. Six
      reconstructions were intercalary, sixteen were resection arthrodeses, three
      followed resection of a bone segment including the epiphysis (osteoarticular
      reconstruction), and one was a replacement of the entire humerus. Resection
      arthrodesis about the knee was performed with a smooth intramedullary rod and
      with one growth plate left intact. Six procedures were performed in the upper
      extremity. Excluding the patients who died, the average duration of follow-up was
      five years and three months. Twenty-one of the twenty-six patients had reached
      skeletal maturity at the time of follow-up. Eighteen (69 per cent) of the
      patients had a good or excellent result, four (15 per cent) had a fair result,
      and four had a failure. Twenty patients (77 per cent) had at least one
      complication (other than a limb-length discrepancy), and fourteen (54 per cent)
      sustained at least one fracture of the allograft. Fifteen patients who had had a
      reconstruction in the lower extremity had survived with survival of the allograft
      at the time of the latest follow-up. A limb-length discrepancy of at least two
      centimeters developed in nine of the fifteen patients. Five were managed with a
      contralateral epiphyseodesis, and one of them had an unsuccessful attempt at limb
      lengthening as well. The patients who had a limb-length discrepancy of more than
      three centimeters at the time of follow-up had been significantly younger (p <
      0.05) at the time of the reconstruction than those who had a smaller discrepancy.
      Three allografts (12 per cent), two of which were implanted early in the series,
      became infected. Soft-tissue coverage is of paramount importance for the
      prevention of infection, and we now routinely perform primary muscle
      (gastrocnemius or latissimus dorsi) transfers when dealing with an inadequate
      muscle envelope. Twelve patients were followed for more than four years (average,
      six years and seven months); they had no complications other than increased limb
      length discrepancy and one subluxation of the shoulder after the first four years
      following the reconstruction. Although the rate of complications is higher than
      in adults, allograft reconstruction remains a useful option for the management of
      skeletally immature individuals.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7822357
TI  - The use of a lateral patellar autologous graft for the repair of a large
      osteochondral defect in the knee.
AB  - An autologous graft from the lateral facet of the patella was used to repair a
      large osteochondral defect of the weight-bearing surface of the femoral condyle
      in ten patients who were then followed for an average of six and one-half years
      (range, four to nine years). Function was improved and symptoms were alleviated
      in all of the patients. Four patients had mild pain in the anterior part of the
      knee and two patients had a flexion deformity, which was 5 degrees in one and 10
      degrees in the other. Small osteophytes developed laterally in five of the
      patients; three of the five had pain in the anterior part of the knee and two had
      a mild lateral patellar tilt.

PMID- 7822358
TI  - Periacetabular and intertrochanteric osteotomy for the treatment of
      osteoarthrosis in dysplastic hips.
AB  - The results of periacetabular osteotomy, with and without intertrochanteric
      osteotomy, performed between January 1984 and December 1990, were reviewed for
      forty-two patients who had osteoarthrosis in a congenitally dysplastic hip. There
      were eight male and thirty-four female patients. The average age of the patients
      at the time of the operation was thirty-seven years (range, eleven to fifty-six
      years). Ten patients had combined periacetabular and intertrochanteric
      osteotomies. The preoperative severity of the osteoarthrosis, according to the
      criteria of Tonnis, was grade 1 in fifteen patients, grade 2 in eighteen, and
      grade 3 in nine. The average duration of follow-up was four years (range, two to
      eight years). Complications included heterotopic ossification in fourteen
      patients (33 per cent), non-union of the pubic osteotomy in two patients (5 per
      cent), and pain related to the hardware that led to its removal in nine patients
      (21 per cent). There were no major neurovascular complications. One patient had
      dysesthesias in the area supplied by the lateral femoral cutaneous nerve. Six
      patients had a subsequent total hip arthroplasty and three patients had an
      additional intertrochanteric osteotomy. five of the nine patients who had a
      second major operation had had grade-3 osteoarthrosis before the periacetabular
      osteotomy. The Harris hip score improved from an average of 62 points (range, 33
      to 95 points) preoperatively to an average of 86 points (range, 29 to 100 points)
      postoperatively (p < 0.0001, paired t test). The result was excellent or good for
      thirty-two of the thirty-three patients who had had grade-1 or 2 osteoarthrosis.
      Eight of the nine patients who had had grade-3 osteoarthrosis had a Harris hip
      score of less than 70 points at the latest follow-up evaluation.

PMID- 7822359
TI  - Total hip replacement with insertion of an acetabular component without cement
      and a femoral component with cement. Four to seven-year results.
AB  - One hundred and fifty-three so-called hybrid total hip replacements were
      performed in 142 patients from 1985 to 1987 at Rush-Presbyterian-St. Luke's
      Medical Center. A hemispherical porous-coated acetabular component was inserted
      without cement and was fixed with screws, and a femoral stem was inserted with
      the use of so-called third-generation cementing techniques. The average age of
      the patients at the time of the operation was sixty-seven years (range, thirty
      nine to eighty-five years). The average preoperative Harris hip score was 46
      points (range, 9 to 73 points). One hundred and eleven patients (120 hips) were
      available for clinical review; 100 of these patients (109 hips) had a complete
      set of radiographs available. The average Harris hip score was 86 points (range,
      29 to 100 points) at the time of follow-up (average duration, sixty-two months;
      range, forty-eight to eighty-five months). There was progressive migration of one
      cup (1 per cent); another cup migrated one centimeter in the first two years
      after the operation, with no additional migration evident after that time. The
      remaining acetabular components were stable. Two femoral components (2 per cent)
      were determined to be definitely loose. The remaining femoral components were
      stable. This population of patients had a good result after so-called hybrid
      total hip replacement with insertion of a porous-coated acetabular component
      without cement and a femoral component with cement for the reconstruction of a
      painful hip.

PMID- 7822360
TI  - The effect of operative fit and hydroxyapatite coating on the mechanical and
      biological response to porous implants.
AB  - Femoral intramedullary implants were constructed by threading 4.0-millimeter
      thick disks with a titanium-alloy (Ti-6Al-4V) porous bead coating onto a two
      millimeter-diameter threaded rod. Each porous-coated disk, which was 6.0, 8.0,
      9.0, or 10.0 millimeters in diameter, was separated by a two-millimeter-thick
      acrylic disk with a diameter of ten millimeters. Implants with and without a
      hydroxyapatite coating of twenty-five micrometers were inserted into fifteen
      skeletally mature adult mongrel dogs. The femoral canal was sequentially reamed
      bilaterally to a ten-millimeter diameter, resulting in uniform initial implant
      bone interface gaps of 0.0, 0.5, 1.0, and 2.0 millimeters. Each animal received
      paired hydroxyapatite-coated and uncoated implants. Three animals each were
      killed at four, eight, twelve, twenty-four, and fifty-two weeks after the
      implantation. The harvested femora were sectioned through the acrylic spacers,
      transverse to the long axis, to produce individual push-out test specimens for
      mechanical testing. Characteristics of interface attachment were determined with
      test fixtures that supported the surrounding bone to within 150 micrometers of
      the interface. Histological sections were prepared, and the amount of bone within
      the porous structure and the amount of the original gap that was filled with new
      bone were quantified with a computerized video image-analysis system. Mechanical
      attachment strength and bone ingrowth were found to increase with the time after
      implantation and with a decrease in the size of the gap. Placement of the implant
      in proximal (cancellous) compared with distal (cortical) locations had no
      significant effect on the strength of attachment, bone ingrowth, or gap-filling.
      However, implants with a large initial gap (1.0 or 2.0 millimeters) demonstrated
      greater attachment strength in cancellous bone than in cortical bone. With a few
      exceptions, hydroxyapatite-coated implants with an initial gap of 1.0 millimeter
      or less demonstrated significantly increased mechanical attachment strength and
      bone ingrowth at all time-periods. Interface attachment strengths were positively
      correlated with bone ingrowth, the time after implantation, the use of a
      hydroxyapatite coating, and decreasing initial gap size. CLINICAL RELEVANCE:
      Initial implant-bone apposition is thought to be a prerequisite for good
      biological fixation. This apposition is often not achieved because of the design
      of the implant or instruments and the operative technique. Poor initial fit
      during the operation may decrease the longevity of the implant. The results of
      the present study indicate that attachment strength and bone ingrowth are
      significantly affected by gaps in the interface, particularly those of more than
      1.0 millimeter.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7822361
TI  - Body-weight related to loss of reduction of fractures of the distal tibia and
      ankle.
AB  - A series of 3061 patients with fracture of the distal tibia or ankle was studied
      for a possible link between overweight and failed reduction. The relative body
      weight was recorded as the preoperative self-reported body mass index (BMI) of
      each patient. There were 109 patients (3.6%) with failure of internal fixation or
      of closed reduction severe enough to necessitate refixation or corrective
      osteotomy. The mean BMI in all age- and gender-specific groups studied was found
      to be significantly higher in patients with failed reduction than in those with
      an uneventful course (p < 0.01). The relative risk of loss of reduction for
      patients with a BMI greater than 1SD above the BMI of the corresponding age and
      gender group of the general population was 3.72 for distal tibial fractures and
      3.04 for ankle fractures. Overweight should be recognised as a significant factor
      in predicting a complicated course after a fracture of the lower leg. Awareness
      of the increased risk of loss of reduction in overweight patients is important in
      all phases of management.

PMID- 7822362
TI  - Fracture of the cuboid in children. A source of leg symptoms.
AB  - We report eight cases of fracture of the cuboid in seven children under four
      years of age, collected during a two-year period. There was no history of trauma
      in five of the patients. This fracture is rarely diagnosed and has probably been
      under-reported. Small children are poor historians and difficult to examine, and
      early radiographs may be normal or have only subtle abnormalities. Cuboid
      fracture should be considered in the differential diagnosis of limping toddlers,
      and a bone scan may be needed to confirm the diagnosis earlier than radiography.
      These fractures heal completely, without sequelae. Treatment in a short-leg
      walking cast is recommended, primarily for reasons of comfort.

PMID- 7822363
TI  - Femoral derotation for increased hip anteversion. A new surgical technique with a
      modified Ilizarov frame.
AB  - We describe a technique of femoral derotation osteotomy performed according to
      the Ilizarov principles of percutaneous corticotomy and fixation with a frame. We
      performed 24 femoral osteotomies in 16 patients, four with cerebral palsy and 12
      with idiopathic femoral anteversion. All had rapid union and there were few
      complications. The advantages of the method include early ambulation, good
      control of rotation and axial alignment, and minimal scarring.

PMID- 7822364
TI  - Early aseptic loosening of uncemented femoral components in primary total hip
      replacement. A review based on the Norwegian Arthroplasty Register.
AB  - The Norwegian Arthroplasty Register recorded 24,408 primary total hip
      replacements from 1987 to 1993; 2907 of them (13%) were performed with uncemented
      femoral components. We have compared the results of eight different designs, each
      used in more than 100 patients. Survivorship of the components was estimated by
      the Kaplan-Meier method using revision for aseptic loosening of the femoral
      component as the end-point. At 4.5 years, the estimated probability of revision
      for aseptic loosening for all implants was 4.5%, for the Bio-Fit stem 18.6% (n =
      210) and for the Femora stem 13.6% (n = 173). The PM-Prosthesis and the
      Harris/Galante stem prostheses needed revision in 5.6% and 3.6%, respectively.
      The clockwise threaded stem of the Femora implant needed revision in 20% of right
      hips, but in only 4% of left hips. The short-term results of the four best
      uncemented femoral components (Corail, LMT, Profile and Zweimuller) were similar
      to those for cemented stems, with revision for loosening in less than 1% at 4.5
      years. The importance of the control of innovative designs and the registration
      of early results is discussed.

PMID- 7822365
TI  - Reciprocating orthoses for children with myelomeningocele. A comparison of two
      types.
AB  - Since 1987, 22 children with myelomeningocele have been fitted with reciprocating
      orthoses. The level of the spinal lesions ranged from T10 to L4 and 13 had
      associated spinal deformities. Twelve of the patients currently use a
      Reciprocating Gait Orthosis, seven use a Hip Guidance Orthosis or Parawalker, one
      has progressed to a Knee Ankle Foot Orthosis, one has died and one has been lost
      to follow-up. The reciprocating orthoses are worn for a mean of 3.5 hours per day
      (1 to 6.5); daily usage by girls is almost twice that by boys. The mean daily
      usage by community walkers is 4.2 hours (13 children) as against 2.8 hours by
      household ambulators (8 children). Active hip flexion is not essential and fixed
      flexion contractures up to 35 degrees can be accommodated. The average breakdown
      rate is 0.45 per year with an average of 1.5 adjustments each year. The average
      annual cost of a reciprocating orthosis is Aus$750 (375 pounds, US$570); this
      includes fabrication, adjustments and repairs.

PMID- 7822366
TI  - Absence of the dorsalis pedis pulse in the parents of children with club foot.
AB  - There is some evidence that the anterior tibial vascular tree is poorly developed
      in children with club foot. We have found a significantly greater prevalence of
      absence of the dorsalis pedis pulse in the parents of such children. We also
      found significantly more tobacco smokers among the club-foot parents than in the
      control group.

PMID- 7822367
TI  - Closing-wedge posterior osteotomy for ankylosing spondylitis. Partial
      corporectomy and transpedicular fixation in 22 cases.
AB  - From 1990 to 1993 we treated 22 consecutive patients who had progressive spinal
      kyphosis due to ankylosing spondylitis by a closing-wedge posterior vertebral
      osteotomy with partial corporectomy of L4 and transpedicular fixation. The
      average correction was 32 degrees (24 to 52) with a mean loss of correction after
      operation of 2.7 degrees (0 to 13). The average operating time was 185 minutes
      (135 to 240) and blood loss was 2500 ml (1200 to 5000). The osteotomy corrected
      all patients sufficiently to allow them to see ahead and their posture was
      improved. There were no fatal complications, but in two cases there was failure
      of the instrumentation and one patient needed reoperation for nerve compression.
      Two deep wound infections required removal of the implant and six patients had
      superficial skin infections under the plaster. The use of a circoelectric bed and
      intermittent prone lying eliminated this problem.

PMID- 7822368
TI  - Unstable degenerative spondylolisthesis of the cervical spine.
AB  - Unstable degenerative spondylolisthesis of the cervical spine is very rare. Slip
      usually occurs at the C3 on C4 or C4 on C5 levels, immediately above a stiff
      lower cervical spine. There are two clinical patterns: that with neurological
      involvement causing cervicobrachial pain or myelopathy and that with neck pain
      alone. The diagnosis can be made by flexion/extension radiography. All of our
      eight patients had localised fusion, three anterior and five posterior, and all
      had satisfactory results one to seven years after operation.

PMID- 7822369
TI  - Oophorectomy predisposes to degenerative spondylolisthesis.
AB  - We performed a case-control study on the influence of oophorectomy on the
      development of degenerative spondylolisthesis, including a clinical review and
      determination of serum oestradiol levels. We also compared the radiological
      appearance of the lumbar spine at L4/5 in patients with and without
      spondylolisthesis and with and without oophorectomy. Oophorectomy was a risk
      factor for degenerative spondylolisthesis with an odds ratio of 7.5 (95%
      confidence interval, 1.6 to 46). The incidence of degenerative spondylolisthesis
      in 69 oophorectomised patients was about three times higher than in 69 non
      oophorectomised matched control subjects. There was also a difference in spinal
      variation between oophorectomised and non-oophorectomised patients with
      spondylolisthesis. A high incidence of sagittal-plane orientation of the L4/5
      facet and an increase in pedicle-facet angle were seen in both groups and are
      typical radiological features of this disease. An increase in lumbosacral angle
      and in disc-space narrowing was seen only in the non-oophorectomised patients
      with this condition. Our results suggest that the abrupt decrease in oestradiol
      level caused by oophorectomy may be a predisposing factor in degenerative
      spondylolisthesis at L4/5.

PMID- 7822370
TI  - Thoracic myelopathy due to isolated ossification of the ligamentum flavum.
AB  - We report a 72-year-old patient with thoracic myelopathy due to isolated
      ossification of the ligamentum flavum at T9-T10. Severe paraparesis had developed
      before the lesion was identified when thinning of a segment of the lower thoracic
      spinal cord was suspected on a second MRI examination. The diagnosis was then
      established by CT.

PMID- 7822371
TI  - Role of melatonin deficiency in the development of scoliosis in pinealectomised
      chickens.
AB  - We studied the possible role of melatonin deficiency in experimentally-induced
      scoliosis. A total of 90 chickens underwent pinealectomy on the third day after
      hatching: 30 were treated with serotonin, 30 with melatonin and 30 received no
      therapy (control group). Scoliosis developed in all the control group, in 22 of
      the serotonin group, and in only 6 of the melatonin group. The six melatonin
      treated chickens with scoliosis had less severe spinal deformities than those in
      the serotonin-treated group. There were lower blood melatonin concentrations in
      chickens with scoliosis than in those without. Our findings suggest that
      melatonin deficiency contributes to the aetiology of this experimental scoliosis,
      probably by interfering with the normally symmetrical growth of the
      proprioceptive system involving the paraspinal muscles and the spine.

PMID- 7822372
TI  - Human bone-cell proliferation in vitro decreases with human donor age.
AB  - We have measured the effect of age on the rate of outgrowth of cells from human
      trabecular bone, using a quantitative dye-binding technique. In cultures
      supplemented with autologous serum, there were significant negative correlations
      between the age of the donor and both the proportion of fragments from which
      outgrowths were seen after 7 days (r = -0.70; p < 0.001) and the total cell
      number after 14 days (r = -0.78; p < 0.005). The autologous serum supported
      greater cell proliferation than did fetal calf serum in all subjects regardless
      of age. Taken with previous observations that the in vitro growth kinetics of
      passaged human bone cells are independent of age, our results show that the
      number of proliferative precursor cells on trabecular-bone surfaces is higher in
      younger subjects. There is a marked decrease in precursor numbers in the second
      and third decades of life to a level which is maintained into old age.

PMID- 7822373
TI  - Bone mineral density in children with mild osteogenesis imperfecta.
AB  - We used dual-energy X-ray absorptiometry (DEXA) to compare the bone mineral
      density (BMD) of nine children aged from 2 years 7 months to 13 years 5 months
      who had mild osteogenesis imperfecta with an age- and sex-matched control group.
      The patients had only mild clinical symptoms but DEXA detected highly significant
      differences in BMD between them and the controls. The mean BMD in the children
      with osteogenesis imperfecta was 76.7% of normal in the lumbar spine (p < 0.001)
      and 71.2% of normal in the femoral neck (p < 0.001). DEXA is an objective,
      reproducible and sensitive method of measurement of BMD in children. It may help
      to establish the diagnosis, to assess prognosis and possibly to monitor the
      response to different types of treatment.

PMID- 7822374
TI  - Biochemical markers of nutrition in type-I and type-II osteoporosis.
AB  - We studied nutritional deficits, using as markers the levels of transferrin,
      retinol-binding protein, and prealbumin, in 20 women with osteoporotic hip
      fractures (type II), 40 women with vertebral fractures (type I), and two groups
      of age-matched control subjects. The concentrations of all three nutritional
      markers were lower in the two groups of patients than in their matched controls,
      and in type-I as compared with type-II osteoporosis. In the osteoporotic
      patients, simple linear regression showed a significant correlation between the
      variables which we studied (r2 ranged from 0.5 to 0.7; p < 0.001), the best
      correlation being between prealbumin and retinol-binding protein in type-II
      osteoporosis. Our results suggest that there is a more marked nutritional deficit
      in type-II than in type-I osteoporosis.

PMID- 7822376
TI  - Stress fracture of the acromion: an unusual mechanism and review of the
      literature.

PMID- 7822375
TI  - The swallow-tail sign: a test of deltoid function.

PMID- 7822378
TI  - Tendon and ligament injuries in adults with osteogenesis imperfecta.

PMID- 7822377
TI  - Suture fixation of osteochondral fractures of the patella.

PMID- 7822379
TI  - Imaging of fractures with external fixators using flexible cassettes.

PMID- 7822380
TI  - Tibiofibular impaction: obstruction to tibial fracture reduction.

PMID- 7822382
TI  - Bifocal fractures of the tibia and fibula.

PMID- 7822381
TI  - Simultaneous bilateral quadriceps rupture: a complication of anabolic steroid
      abuse.

PMID- 7822383
TI  - Traction lesions of nerves.

PMID- 7822384
TI  - Antiplatelet therapy to prevent thrombosis after hip fracture.

PMID- 7822385
TI  - Central grafting for tibial nonunion.

PMID- 7822386
TI  - Osteotomy for hallux valgus.

PMID- 7822387
TI  - Mycobacterium avium intracellulare infection.

PMID- 7822388
TI  - Failure of the cement-bone interface.

PMID- 7822389
TI  - Migration of the Charnley stem in rheumatoid arthritis and osteoarthritis. A
      roentgen stereophotogrammetric study.
AB  - Migration of 65 Charnley stems implanted with modern cementing techniques was
      studied by roentgen stereophotogrammetry. There were 25 patients with rheumatoid
      arthritis (RA) and 40 with osteoarthritis (OA) followed up for two years. In 43
      cases a bone sample for histomorphometric analysis was obtained from the femur
      during the operation. In 22 cases the mean subsidence of the prosthetic head was
      0.40 mm and in 20 the mean posterior migration was 1.25 mm. There was no
      difference in migration between the two diagnostic groups (p = 0.8) after
      adjusting for variations in gender, age and weight. Male gender was associated
      with increased subsidence (p = 0.006). Histological examination showed that the
      RA series had more osteoid surface (p = 0.04), but neither this, nor any of the
      other histomorphometric variables, influenced migration. These results suggest
      that, unlike the acetabular socket, the cemented Charnley femoral component is
      equally secure in osteoarthritis and in rheumatoid arthritis, and that its
      initial fixation is not influenced by the quality of the local cancellous bone.
      Our results provide data with which the early performance of new prosthetic
      designs and fixation methods can be compared.

PMID- 7822390
TI  - Revision for aseptic stem loosening using the cemented Charnley prosthesis. A
      review of 351 hips.
AB  - We reviewed 351 cemented revisions of femoral stems performed for aseptic
      loosening. At a mean of six years after the revision operation 72.1% of the
      patients were pain-free and 21.4% had only mild or occasional discomfort. The
      latest radiographs showed definite stem loosening in 10 (2.8%) and 20 hips (5.7%)
      had required rerevision, only nine (2.6%) of which were for mechanical failure of
      the stem. Survivorship analysis, taking the end point as rerevision of the stem,
      gave 97.0% survival at eight years and 91.6% at 11 years. Excellent results both
      clinically and radiologically can be achieved by cemented revision of the femoral
      stem for aseptic loosening.

PMID- 7822391
TI  - Diagnosis of infection by frozen section during revision arthroplasty.
AB  - We assessed the efficacy of intraoperative frozen-section histology in detecting
      infection in failed arthroplasties in 106 hips and knees. We found inflammatory
      changes consistent with infection (an average of one or more neutrophil
      polymorphs or plasma cells per high-power field in several samples) in 18 cases;
      there was a significant growth on bacterial culture in 20 cases. Compared with
      the bacterial cultures, the frozen sections provided two false-negative results
      and three false-positive results (sensitivity, 90%; specificity, 96%; and
      accuracy, 95%). The positive predictive value was 88%, the negative value, 98%.
      These results support the inclusion of intra-operative frozen-section histology
      in any protocol for revision arthroplasty for loose components.

PMID- 7822392
TI  - Pharmacological thromboprophylaxis and total hip replacement.

PMID- 7822393
TI  - A quantitative system for staging avascular necrosis.
AB  - Much of the current confusion and contradiction on the treatment of avascular
      necrosis of the femoral head is caused by the lack of an agreed efficient,
      quantitative system for evaluation and staging. We have used a new system to
      evaluate over 1000 hips with avascular necrosis during a period of 12 years; it
      has proved to be very valuable. The system is based on the sequence of
      pathological events known to take place. It allows accurate quantification in
      both early and later stages, does not use older, invasive diagnostic procedures,
      and incorporates the newer techniques of bone scanning and MRI. Clinical records
      of pain and reduced function are not a specific part of the system, although they
      help to determine treatment and outcome. Hips are first placed into one of seven
      stages from 0 to VI, based upon the type of radiological change. The extent of
      involvement is then measured. This allows more accurate evaluation of progression
      or resolution and better comparison of different methods of management. The
      system also helps to provide a prognosis and to decide on the best available
      method of treatment.

PMID- 7822394
TI  - Long-term results of core decompression for ischaemic necrosis of the femoral
      head.
AB  - We have studied the long-term results of core decompression as the sole treatment
      for Ficat stages I, II and III ischaemic necrosis of 128 femoral heads in 90
      patients. The 5-, 10- and 15-year survival rates for the three stages were
      respectively: stage I 100%, 96% and 90%; stage II 85%, 74% and 66%; and stage III
      58%, 35% and 23%. At a mean follow-up of 11 years (4.5 to 19), 55 hips had failed
      (43%). No further surgery had been needed for 88% of stage-I, 72% of stage-II and
      26% of stage-III hips; but despite the generally satisfactory clinical results,
      56% of the hips had progressed radiographically by at least one Ficat stage.
      Complications of the core procedure included four fractures, all from
      postoperative falls, and one head perforation due to technical error. We conclude
      that core decompression delays the need for total hip replacement in young
      patients with ischaemic necrosis.

PMID- 7822395
TI  - Low tibial osteotomy for osteoarthritis of the ankle. Results of a new operation
      in 18 patients.
AB  - Primary osteoarthritis of the ankle with no history of trauma is rare. We report
      the use of a low tibial osteotomy on 18 ankles in 18 patients, two men and 16
      women. The osteotomy is designed to correct the varus tilt and anterior opening
      of the distal tibial joint surface where it has been shown by weight-bearing
      radiographs and arthroscopy that there is healthy articular cartilage on the
      lateral side of the ankle. An opening-wedge osteotomy was used to achieve slight
      overcorrection. Follow-up of the 18 ankles at an average of 6 years 11 months
      (2.7 to 12.10) showed the results by our own scoring system to be excellent in
      six ankles, good in nine, and fair in three with no poor results. Of the three
      patients with fair results, two had been undercorrected and the third had little
      residual articular cartilage. Arthroscopic examination of ten ankles showed
      repair by fibrocartilage in seven. We conclude that slight overcorrection of
      deformity by low tibial osteotomy is effective in treating intermediate-stage
      primary osteoarthritis of the ankle.

PMID- 7822396
TI  - A new operation for chronic lateral ankle instability.
AB  - We have treated 45 patients (47 ankles) for chronic lateral instability by a new
      reconstructive procedure. The operation includes lateral shift of the entire
      lateral capsule-ligament complex and proximal advancement of the talocalcaneal
      ligament and the inferior extensor retinaculum. We reviewed 39 patients (39
      ankles) at a mean of 4.6 years (2 to 7) after operation. There were 29 men and 10
      women with an average age of 27 years (19 to 43); 11 of them were competitive
      college-level athletes and 28 were recreational athletes. The functional rating
      was excellent in 26 patients, good in 8, fair in 3 and poor in 2. Thirty-six
      patients (92%) were satisfied with the result and 34 (9 of 11 college-level
      athletes and 25 of 28 recreational athletes) have been able to return to their
      preinjury level of sport. At the last review, there had been only three episodes
      of recurrent ankle instability, all in recreational athletes; none had required
      further surgery. The unsatisfactory results were associated with pre-existing
      degenerative changes in the ankle.

PMID- 7822397
TI  - Death and thromboembolic disease after total hip replacement. A series of 1162
      cases with no routine chemical prophylaxis.
AB  - We studied 1162 consecutive total hip replacements (THR) to establish the
      incidence of fatal pulmonary embolism (PE), clinical non-fatal PE and deep-vein
      thrombosis (DVT) in the six months after surgery. Chemical thromboprophylaxis had
      not been routinely used. We used a validated questionnaire supplemented by post
      mortem records and a review of the clinical notes. Follow-up was 100%. The death
      rate from PE was 0.34% (95% CI 0.09 to 0.88), with one fatal PE after discharge
      40 days after operation. The clinical PE rate confirmed by imaging was 1.20% (CI
      0.65 to 2.02), with 0.7% of patients readmitted. The venographically-confirmed
      clinical DVT rate was 1.89% (CI 1.11 to 2.76), with 1.13% readmitted. The total
      thromboembolic morbidity was 3.4% (95% CI 2.5% to 4.7%); prophylaxis to reduce
      this would be justifiable if the complications of such prophylaxis did not
      produce an alternative morbidity. The fatal PE rate after THR without routine
      chemical prophylaxis was low; a very large randomised clinical trial would be
      required to demonstrate directly whether any prophylactic measure could reduce
      this. There is a large discrepancy between the high DVT rate reported in clinical
      trials using universal screening venography and the symptomatic DVT rate shown in
      this study. We found insufficient evidence to recommend continuing
      thromboprophylaxis after discharge from hospital.

PMID- 7822398
TI  - A combined open and percutaneous technique for repair of tendo Achillis.
      Comparison with open repair.
AB  - A combined open and percutaneous operative technique has been devised for repair
      of tendo Achillis. This minimises postoperative scarring. We compared the long
      term results of 12 patients treated by this method with the results of 10 who had
      undergone an open repair. The combined open and percutaneous repair gave
      significantly better relief of symptoms during everyday activities (p < 0.05),
      better single-limb hopping (p < 0.02) and a greater chance of returning to sport
      (p < 0.01). There were no significant differences between the two treatments as
      regards to active range of ankle motion, calf circumference or the ability to
      stand on tiptoe. The new technique gave better cosmetic results.

PMID- 7822399
TI  - Tissue expansion in late repair of tendo Achillis rupture.

PMID- 7822400
TI  - Semiconstrained elbow replacement for distal humeral nonunion.
AB  - We have reviewed 36 of 39 consecutive patients with an average age of 68 years
      who had semiconstrained elbow replacement for distal humeral nonunion at an
      average follow-up of 50.4 months (24 to 127). Of these, 31 (86%) had satisfactory
      results, three (8%) had fair, and two (6%) had poor results; 32 patients (88%)
      had moderate or severe pain before and 91% had no or only mild discomfort after
      the procedure. Motion had improved from a mean arc of 29 degrees to 103 degrees
      before operation to 16 degrees to 127 degrees after surgery. All five flail
      extremities were stable at last assessment. There were seven complications (18%):
      two patients had deep infection, two had particulate synovitis, two had ulnar
      neuropathy and one had worn polyethylene bushes. Five of these seven, excluding
      the two with transient nueropathy, required reoperation (13%). Joint replacement
      arthroplasty can be a safe and reliable treatment for this difficult clinical
      condition, seen most commonly in elderly patients. This is a significant advance,
      since repeated osteosynthesis has been shown to be ineffective in most patients.

PMID- 7822401
TI  - Coracoid transposition for recurrent anterior instability of the shoulder. A 20
      year follow-up study.
AB  - We report the 20-year results of Bonnin's modification of the Bristow-Latarjet
      procedure in 14 patients operated on by one surgeon. All but one patient had had
      traumatic dislocations. At review, the Rowe scores were excellent in five, good
      in eight and fair in one. The functional outcome was satisfactory, with a mean
      Constant-Murley score of 80 points (68 to 95), but 12 patients had restriction of
      external rotation (86%). There were radiological degenerative changes in ten
      shoulders (71%): six in Samilson grade I, one in grade II, and three in grade
      III. Isometric power was considerably reduced in patients with grade-III
      degenerative change. This operation provides good long-term shoulder stability,
      but the high incidence of radiological degenerative change is a cause for
      concern.

PMID- 7822402
TI  - Sonography of the injured ulnar collateral ligament of the thumb.
AB  - We used high-resolution ultrasonography to image the ulnar collateral ligament in
      39 patients who had sustained recent injuries of the metacarpophalangeal joint of
      the thumb. All the patients were subsequently operated on and the lesions of the
      ligament were recorded. In 36 patients the preoperative ultrasonographic
      diagnosis was correct. Five of these showed no rupture of the ligament. In the
      other 31, ultrasonography correctly distinguished between rupture in situ (15)
      and rupture with dislocation of the ligament (16). Misdiagnosis by
      ultrasonography in three cases was due to delay of the investigation (three weeks
      after injury) in one, to technical error in one and to misinterpretation of the
      image in one.

PMID- 7822403
TI  - Retrograde locked nailing of humeral shaft fractures. A review of 39 patients.
AB  - We treated 39 patients with fractures of the humeral shaft by closed retrograde
      locked intramedullary nailing, using Russell-Taylor humeral nails. The mean
      healing time of all fractures was 13.7 weeks. After consolidation, shoulder
      function was excellent in 92.3% and elbow function excellent in 87.2%. Functional
      end-results were excellent in 84.6% of patients, moderate in 10.3% and bad in
      5.1%. One patient had a postoperative radial nerve palsy, which recovered within
      three months. There was additional comminution at the fracture site in three
      patients (7.7%) which did not affect healing, and slight nail migration in two
      older patients (5.1%). Two patients (5.1%) needed a second procedure because of
      disturbed fracture healing. One screw breakage was seen in a patient with delayed
      union. Retrograde locked humeral nailing appears to be a better solution for the
      stabilisation of fractures of the humeral shaft than anterograde nailing or plate
      and screw fixation. We found the complication rate to be acceptable and shoulder
      and elbow function to recover rapidly in most cases.

PMID- 7822404
TI  - Nonunion of intertrochanteric fractures of the femur. Treatment by modified
      medial displacement and valgus osteotomy.
AB  - Nonunion of intertrochanteric fractures is uncommon but its effects are
      disabling. We describe a modification of the medial displacement and valgus
      osteotomy of Dimon and Hughston (1967) which we used in seven fractures, six of
      which united within 16 weeks. Postoperatively, hip function was good. The method
      provides good initial stability, a source of cancellous bone graft, good
      postoperative hip abductor function and reliable healing of the nonunion without
      the need for intraoperative imaging.

PMID- 7822405
TI  - Local antibiotic therapy for severe open fractures. A review of 1085 consecutive
      cases.
AB  - We reviewed 1085 consecutive compound limb fractures treated in 914 patients at
      the University of Louisville over a nine-year period. Of these fractures, 240
      (group 1) received only systemic antibiotic prophylaxis and 845 (group 2) were
      managed by the supplementary local use of aminoglycoside-polymethylmethacrylate
      (PMMA) beads. There were no significant differences in age, gender, fracture
      type, fracture location or follow-up between the two groups. All had copious
      wound irrigation, meticulous debridement and skeletal stabilisation, but wound
      management and the use of local antibiotic depended on the surgeon's individual
      preference and there was no randomisation. In group 1 there was an overall
      infection rate of 12% as against 3.7% in group 2 (p < 0.001). Both acute
      infection and local osteomyelitis showed a decreased incidence in group 2, but
      this was statistically significant only in Gustilo type-IIIB and type-IIIC
      fractures for acute infection, and only in type-II and type-IIIB fractures for
      chronic osteomyelitis. Our review suggests that the adjuvant use of local
      antibiotic-laden PMMA beads may reduce the incidence of infection in severe
      compound fractures.

PMID- 7822406
TI  - Nonunion of the scaphoid in children treated by Herbert screw fixation and bone
      grafting. A report of five cases.
AB  - In children, nonunion of fractures of the waist of the scaphoid is uncommon.
      Treatment has included bone grafting without internal fixation, bone grafting
      with Kirschner-wire fixation, and screw fixation without bone grafting. We report
      the successful use of Herbert screw fixation and iliac-crest bone grafting in
      five cases, all of which healed without further surgery. At an average follow-up
      of 3.3 years, the range of motion, grip strength, carpal stability, and
      radiological appearances were all excellent.

PMID- 7822407
TI  - A new role for motor proteins as couplers to depolymerizing microtubules.

PMID- 7822408
TI  - Antibodies to the kinesin motor domain and CENP-E inhibit microtubule
      depolymerization-dependent motion of chromosomes in vitro.
AB  - Chromosomes can move with the ends of depolymerizing microtubules (MTs) in vitro,
      even in the absence of nucleotide triphosphates (Coue, M., V. A. Lombillo, and J.
      R. McIntosh. 1991. J. Cell Biol. 112:1165-1175.) Here, we describe an
      immunological investigation of the proteins important for this form of motility.
      Affinity-purified polyclonal antibodies to kinesin exert a severe inhibitory
      effect on depolymerization-dependent chromosome motion. These antibodies
      predominantly recognize a polypeptide of M(r) approximately 250 kD on immunoblots
      of CHO chromosomes and stain kinetochores as well as some vesicles that are in
      the chromosome preparation. Antibodies to CENP-E, a kinetochore-associated
      kinesin-like protein, also recognize a 250-kD electrophoretic component, but they
      stain only the kinetochroe region of isolated chromosomes. Polyclonal antibodies
      that recognize specific domains of the CENP-E polypeptide affect MT disassembly
      dependent chromosome motion in different ways; antibodies to the head or tail
      portions slow motility threefold, while those raised against the neck region stop
      motion completely. Analogous antibodies that block conventional, ATP-dependent
      motility of cytoplasmic dynein (Vaisberg, G., M. P. Koonce, and J. R. McIntosh.
      1993. J. Cell Biol. 123:849-858) have no effect on disassembly-dependent
      chromosome motion, even though they bind to kinetochores. These observations
      suggest that CENP-E helps couple chromosomes to depolymerizing MTs. A similar
      coupling activity may allow spindle MTs to remain kinetochore-bound while their
      lengths change during both prometaphase and anaphase A.

PMID- 7822409
TI  - Structural changes accompanying GTP hydrolysis in microtubules: information from
      a slowly hydrolyzable analogue guanylyl-(alpha,beta)-methylene-diphosphonate.
AB  - We have used cryoelectron microscopy to try to understand the structural basis
      for the role of GTP hydrolysis in destabilizing the microtubule lattice. We have
      measured a structural difference introduced into microtubules by replacing GTP
      with guanylyl-(alpha,beta)-methylene-diphosphonate (GMPCPP). In a stable GMPCPP
      microtubule lattice, the moire patterns change and the tubulin subunits increase
      in size by 1.5 A. This information provides a clue to the role of hydrolysis in
      inducing the structural change at the end of a microtubule during the transition
      from a growing to a shrinking phase.

PMID- 7822410
TI  - The role of microtubules in growth cone turning at substrate boundaries.
AB  - To understand the role of microtubules in growth cone turning, we observed
      fluorescently labeled microtubules in neurons as they encountered a substrate
      boundary. Neurons growing on a laminin-rich substrate avoided growing onto
      collagen type IV. Turning growth cones assumed heterogeneous morphologies and
      behaviors that depended primarily in their extent of adhesion to the substrate.
      We grouped these behaviors into three categories-sidestepping, motility, and
      growth-mediated reorientation. In sidestepping and motility-mediated
      reorientation, the growth cone and parts of the axon were not well attached to
      the substrate so the acquisition of an adherent lamella caused the entire growth
      cone to move away from the border and consequently reoriented the axon. In these
      cases, since the motility of the growth cone dominates its reorientation, the
      microtubules were passive, and reorientation occurred without significant axon
      growth. In growth-mediated reorientation, the growth cone and axon were attached
      to the substrate. In this case, microtubules reoriented within the growth cone to
      stabilize a lamella. Bundling of the reoriented microtubules was followed by
      growth cone collapse to form new axon, and further, polarized lamellipodial
      extension. These observations indicate that when the growth cone remains adherent
      to the substrate during turning, the reorientation and bundling of microtubules
      is an important, early step in growth cone turning.

PMID- 7822411
TI  - The role of microtubule dynamics in growth cone motility and axonal growth.
AB  - The growth cone contains dynamic and relatively stable microtubule populations,
      whose function in motility and axonal growth is uncharacterized. We have used
      vinblastine at low doses to inhibit microtubule dynamics without appreciable
      depolymerization to probe the role of these dynamics in growth cone behavior. At
      doses of vinblastine that interfere only with dynamics, the forward and
      persistent movement of the growth cone is inhibited and the growth cone wanders
      without appreciable forward translocation; it quickly resumes forward growth
      after the vinblastine is washed out. Direct visualization of fluorescently tagged
      microtubules in these neurons shows that in the absence of dynamic microtubules,
      the remaining mass of polymer does not invade the peripheral lamella and does not
      undergo the usual cycle of bundling and splaying and the growth cone stops
      forward movement. These experiments argue for a role for dynamic microtubules in
      allowing microtubule rearrangements in the growth cone. These rearrangements seem
      to be necessary for microtubule bundling, the subsequent coalescence of the
      cortex around the bundle to form new axon, and forward translocation of the
      growth cone.

PMID- 7822412
TI  - Nuclear spreads: I. Visualization of bipartite ribosomal RNA domains.
AB  - Visualization of nuclear architecture is key to the understanding of the
      association between RNA synthesis and processing. This architecture is obscured
      by the high density of components in most nuclei. We have developed a method of
      spreading nuclei and nucleoli that reduces overlap of weakly associated
      components. Strong interactions among nuclear components are not disrupted by
      this method. Spread nucleoli remained structurally distinct and functionally
      competent in ribosomal RNA synthesis. Nascent ribosomal RNA colocalized with RNA
      polymerase I and fibrillarin, a protein required for processing of ribosomal RNA.
      Colocalization of nascent transcripts and fibrillarin was seen in nucleoli spread
      over several microns, suggesting a strong interaction. These data suggest that
      nucleoli are superassemblies of bipartite domains, each composed of a ribosomal
      RNA synthesis center tightly associated with areas likely to be involved in
      ribosomal RNA processing.

PMID- 7822413
TI  - Roles of hepatocyte growth factor/scatter factor and the met receptor in the
      early development of the metanephros.
AB  - Several lines of evidence suggest that hepatocyte growth factor/scatter factor
      (HGF/SF), a soluble protein secreted by embryo fibroblasts and several fibroblast
      lines, may elicit morphogenesis in adjacent epithelial cells. We investigated the
      role of HGF/SF and its membrane receptor, the product of the c-met protooncogene,
      in the early development of the metanephric kidney. At the inception of the mouse
      metanephros at embryonic day 11, HGF/SF was expressed in the mesenchyme, while
      met was expressed in both the ureteric bud and the mesenchyme, as assessed by
      reverse transcription PCR, in situ hybridization, and immunohistochemistry. To
      further investigate the expression of met in renal mesenchyme, we isolated 13
      conditionally immortal clonal cell lines from transgenic mice expressing a
      temperature-sensitive mutant of the SV-40 large T antigen. Five had the
      HGF/SF+/met+ phenotype and eight had the HGF/SF-/met+ phenotype. None had the
      HGF/SF+/met- nor the HGF/SF-/met- phenotypes. Thus the renal mesenchyme contains
      cells that express HGF/SF and met or met alone. When metanephric rudiments were
      grown in serum-free organ culture, anti-HGF/SF antibodies (a) inhibited the
      differentiation of metanephric mesenchymal cells into the epithelial precursors
      of the nephron; (b) increased cell death within the renal mesenchyme; and (c)
      perturbed branching morphogenesis of the ureteric bud. These data provide the
      first demonstration for coexpression of the HGF/SF and met genes in mesenchymal
      cells during embryonic development and also imply an autocrine and/or paracrine
      role for HGF/SF and met in the survival of the renal mesenchyme and in the
      mesenchymal-epithelial transition that occurs during nephrogenesis. They also
      confirm the postulated paracrine role of HGF/SF in the branching of the ureteric
      bud.

PMID- 7822414
TI  - Identification of brain-derived neurotrophic factor promoter regions mediating
      tissue-specific, axotomy-, and neuronal activity-induced expression in transgenic
      mice.
AB  - The structure of rat brain-derived neurotrophic factor (BDNF) gene is complex;
      four 5' exons are linked to separate promoters and one 3' exon is encoding the
      BDNF protein. To analyze the relative importance of the regulatory regions in
      vivo, we have generated transgenic mice with six different promoter constructs of
      the BDNF gene fused to the chloramphenicol acetyl transferase reporter gene. High
      level and neuronal expression of the reporter gene, that in many respects
      recapitulated BDNF gene expression, was achieved by using 9 kb of genomic
      sequences covering the promoter regions that lie adjacent to each other in the
      genome (promoters I and II and promoters III and IV, respectively) and by
      including sequences of BDNF intron-exon splice junctions and 3' untranslated
      region in the constructs. The genomic regions responsible for the in vivo
      upregulation of BDNF expression in the axotomized sciatic nerve and in the brain
      after kainic acid-induced seizures and KCl-induced spreading depression were
      mapped. These data show that regulation of the different aspects of BDNF
      expression is controlled by different regions in vivo, and they suggest that
      these promoter constructs may be useful for targeted expression of heterologous
      genes to specific regions of the central and peripheral nervous systems in an
      inducible manner.

PMID- 7822415
TI  - Viral proteins E1B19K and p35 protect sympathetic neurons from cell death induced
      by NGF deprivation.
AB  - To study molecular mechanisms underlying neuronal cell death, we have used
      sympathetic neurons from superior cervical ganglia which undergo programmed cell
      death when deprived of nerve growth factor. These neurons have been microinjected
      with expression vectors containing cDNAs encoding selected proteins to test their
      regulatory influence over cell death. Using this procedure, we have shown
      previously that sympathetic neurons can be protected from NGF deprivation by the
      protooncogene Bcl-2. We now report that the E1B19K protein from adenovirus and
      the p35 protein from baculovirus also rescue neurons. Other adenoviral proteins,
      E1A and E1B55K, have no effect on neuronal survival. E1B55K, known to block
      apoptosis mediated by p53 in proliferative cells, failed to rescue sympathetic
      neurons suggesting that p53 is not involved in neuronal death induced by NGF
      deprivation. E1B19K and p35 were also coinjected with Bcl-Xs which blocks Bcl-2
      function in lymphoid cells. Although Bcl-Xs blocked the ability of Bcl-2 to
      rescue neurons, it had no effect on survival that was dependent upon expression
      of E1B19K or p35.

PMID- 7822416
TI  - NCAM polypeptides in heart development: association with Z discs of forms that
      contain the muscle-specific domain.
AB  - Previous studies of neural cell adhesion molecule (NCAM) cDNAs have revealed an
      alternatively spliced set of small exons (12A, 12B, 12C, and 12D) that encode a
      region in the extracellular portion of the molecule known as the muscle-specific
      domain (MSD). The entire MSD region can be expressed in skeletal muscle, heart,
      and skin; only exons 12A and 12D have been found in brain. These studies did not
      reveal which NCAM polypeptides contain the MSD region or the immunohistochemical
      distribution of these NCAM molecules. To address these questions, we prepared
      antibodies against the oligopeptides encoded by exons 12A and 12B and by exons
      12C and 12D, and we used these antibodies to study the forms of NCAM containing
      the MSD region expressed during embryonic chicken heart development. These
      antibodies recognize certain forms of NCAM found in the heart, but they do not
      recognize brain NCAM. In the heart, each of the splice variants of NCAM (large
      cytoplasmic domain, small cytoplasmic domain, and small surface domain) that
      differ in their mode of attachment to the plasma membrane or in the size of their
      cytoplasmic domain is expressed in a form that contains and in a form that lacks
      the MSD region. No microheterogeneity is observed in the size of NCAM molecules
      containing the MSD region, even at the level of cyanogen bromide fragments,
      suggesting that exons 12A-D are expressed as a single unit. Depending on the site
      and the stage of development, the percent of NCAM molecules containing the MSD
      region can vary from nearly 0 to 100%. In general, this percentage increases
      during development. In immunohistochemical studies of hearts from stage 18
      embryos, forms of NCAM containing the MSD region colocalized with Z discs. No
      other adhesion molecules were found in this distribution at this early stage of
      development. Studies on isolated cells in vitro demonstrate that the
      colocalization with Z discs of NCAM molecules containing the MSD region does not
      depend on cell-cell contact, and they raise the possibility that this form of
      NCAM is involved in cell-extracellular matrix interactions. The association of
      NCAM molecules containing the MSD region with Z discs suggests that this form of
      NCAM is involved in early myofibrillogenesis.

PMID- 7822417
TI  - Human COL2A1-directed SV40 T antigen expression in transgenic and chimeric mice
      results in abnormal skeletal development.
AB  - The ability of SV40 T antigen to cause abnormalities in cartilage development in
      transgenic mice and chimeras has been tested. The cis-regulatory elements of the
      COL2A1 gene were used to target expression of SV40 T antigen to differentiating
      chondrocytes in transgenic mice and chimeras derived from embryonal stem (ES)
      cells bearing the same transgene. The major phenotypic consequences of transgenic
      (pAL21) expression are malformed skeleton, disproportionate dwarfism, and
      perinatal/neonatal death. Expression of T antigen was tissue specific and in the
      main characteristic of the mouse alpha 1(II) collagen gene. Chondrocyte densities
      and levels of alpha 1(II) collagen mRNAs were reduced in the transgenic mice.
      Islands of cells which express cartilage characteristic genes such as type IIB
      procollagen, long form alpha 1(IX) collagen, alpha 2(XI) collagen, and aggrecan
      were found in the articular and growth cartilages of pAL21 chimeric fetuses and
      neonates. But these cells, which were expressing T antigen, were not properly
      organized into columns of proliferating chondrocytes. Levels of alpha 1(II)
      collagen mRNA were reduced in these chondrocytes. In addition, these cells did
      not express type X collagen, a marker for hypertrophic chondrocytes. The skeletal
      abnormality in pAL21 mice may therefore be due to a retardation of chondrocyte
      maturation or an impaired ability of chondrocytes to complete terminal
      differentiation and an associated paucity of some cartilage matrix components.

PMID- 7822418
TI  - Type X collagen gene expression in mouse chondrocytes immortalized by a
      temperature-sensitive simian virus 40 large tumor antigen.
AB  - Mouse endochondral chondrocytes were immortalized with a temperature-sensitive
      simian virus 40 large tumor antigen. Several clonal isolates as well as pools of
      immortalized cells were characterized. In monolayer cultures at the temperature
      permissive for the activity of the large tumor antigen (32 degrees C), the cells
      grew continuously with a doubling time of approximately 2 d, whereas they stopped
      growing at nonpermissive temperatures (37 degrees C-39 degrees C). The cells from
      all pools and from most clones expressed the genes for several markers of
      hypertrophic chondrocytes, such as type X collagen, matrix Gla protein, and
      osteopontin, but had lost expression of type II collagen mRNA and failed to be
      stained by alcian blue which detects cartilage-specific proteoglycans. The cells
      also contained mRNAs for type I collagen and bone Gla protein, consistent with
      acquisition of osteoblastic-like properties. Higher levels of mRNAs for type X
      collagen, bone Gla protein, and osteopontin were found at nonpermissive
      temperatures, suggesting that the expression of these genes was upregulated upon
      growth arrest, as is the case in vivo during chondrocyte hypertrophy. Cells also
      retained their ability to respond to retinoic acid, as indicated by retinoic acid
      dose-dependent and time-dependent increases in type X collagen mRNA levels. These
      cell lines, the first to express characteristic features of hypertrophic
      chondrocytes, should be very useful to study the regulation of the type X
      collagen gene and other genes activated during the last stages of chondrocyte
      differentiation.

PMID- 7822419
TI  - Calnexin and BiP act as sequential molecular chaperones during thyroglobulin
      folding in the endoplasmic reticulum.
AB  - Before secretion, newly synthesized thyroglobulin (Tg) folds via a series of
      intermediates: disulfide-linked aggregates and unfolded monomers-->folded
      monomers-->dimers. Immediately after synthesis, very little Tg associated with
      calnexin (a membrane-bound molecular chaperone in the ER), while a larger
      fraction bound BiP (a lumenal ER chaperone); dissociation from these chaperones
      showed superficially similar kinetics. Calnexin might bind selectively to
      carbohydrates within glycoproteins, or to hydrophobic surfaces of secretory
      proteins while they form proper disulfide bonds (Wada, I., W.-J. Ou, M.-C. Liu,
      and G. Scheele, J. Biol. Chem. 1994. 269:7464-7472). Because Tg has multiple
      disulfides, as well as glycans, we tested a brief exposure of live thyrocytes to
      dithiothreitol, which resulted in quantitative aggregation of nascent Tg, as
      analyzed by SDS-PAGE of cells lysed without further reduction. Cells lysed in the
      presence of dithiothreitol under non-denaturing conditions caused Tg aggregates
      to run as reduced monomers. For cells lysed either way, after in vivo reduction,
      Tg coprecipitated with calnexin. After washout of dithiothreitol, nascent Tg
      aggregates dissolved intracellularly and were secreted ultimately. 1 h after
      washout, > or = 92% of labeled Tg was found to dissociate from calnexin, while
      the fraction of labeled Tg bound to BiP rose from 0 to approximately 40%,
      demonstrating a "precursor-product" relationship. Whereas intralumenal reduction
      was essential for efficient Tg coprecipitation with calnexin, Tg glycosylation
      was not required. These data are among the first to demonstrate sequential
      chaperone function involved in conformational maturation of nascent secretory
      proteins within the ER.

PMID- 7822420
TI  - Targeting of the yeast plasma membrane [H+]ATPase: a novel gene AST1 prevents
      mislocalization of mutant ATPase to the vacuole.
AB  - We have characterized a class of mutations in PMA1, (encoding plasma membrane
      ATPase) that is ideal for the analysis of membrane targeting in Saccharomyces
      cerevisiae. This class of pma1 mutants undergoes growth arrest at the restrictive
      temperature because newly synthesized ATPase fails to be targeted to the cell
      surface. Instead, mutant ATPase is delivered to the vacuole, where it is
      degraded. Delivery to the vacuole occurs without previous arrival at the plasma
      membrane because degradation of mutant ATPase is not prevented when
      internalization from the cell surface is blocked. Disruption of PEP4, encoding
      vacuolar proteinase A, blocks ATPase degradation, but fails to restore growth
      because the ATPase is still improperly targeted. One of these pma1 mutants was
      used to select multicopy suppressors that would permit growth at the
      nonpermissive temperature. A novel gene, AST1, identified by this selection,
      suppresses several pma1 alleles defective for targeting. The basis for
      suppression is that multicopy AST1 causes rerouting of mutant ATPase from the
      vacuole to the cell surface. pma1 mutants deleted for AST1 have a synthetic
      growth defect at the permissive temperature, providing genetic evidence for
      interaction between AST1 and PMA1. Ast1 is a cytoplasmic protein that associates
      with membranes, and is localized to multiple compartments, including the plasma
      membrane. The identification of AST1 homologues suggests that Ast1 belongs to a
      novel family of proteins that participates in membrane traffic.

PMID- 7822421
TI  - Depletion of calcium from the lumen of endoplasmic reticulum reversibly inhibits
      passive diffusion and signal-mediated transport into the nucleus.
AB  - Nuclear pore complexes provide channels for molecular transport across the
      nuclear envelope. Translocation of most proteins and RNAs through the pore
      complex is mediated by signal- and ATP-dependent mechanisms, while transport of
      small molecules is accomplished by passive diffusion. We report here that
      depletion of calcium from the lumen of the endoplasmic reticulum and nuclear
      envelope with ionophores or the calcium pump inhibitor thapsigargin rapidly and
      potently inhibits signal mediated transport of proteins into the nucleus. Lumenal
      calcium depletion also inhibits passive diffusion through the pore complex.
      Signal-mediated protein import and passive diffusion are rapidly restored when
      the drugs depleting lumenal calcium are removed and cells are incubated at 37
      degrees C in calcium-containing medium. These results indicate that loss of
      calcium from the lumen of the endoplasmic reticulum and nuclear envelope
      reversibly affects properties of pore complex components located on the
      nuclear/cytoplasmic membrane surfaces, and they provide direct functional
      evidence for conformational flexibility of the pore complex. These methods will
      be useful for achieving reversible inhibition of nucleocytoplasmic trafficking
      for in vivo functional studies, and for studying the structure of the passive
      diffusion channel(s) of the pore complex.

PMID- 7822422
TI  - Sequence and domain organization of scruin, an actin-cross-linking protein in the
      acrosomal process of Limulus sperm.
AB  - The acrosomal process of Limulus sperm is an 80-microns long finger of membrane
      supported by a crystalline bundle of actin filaments. The filaments in this
      bundle are crosslinked by a 102-kD protein, scruin present in a 1:1 molar ratio
      with actin. Recent image reconstruction of scruin decorated actin filaments at 13
      A resolution shows that scruin is organized into two equally sized domains bound
      to separate actin subunits in the same filament. We have cloned and sequenced the
      gene for scruin from a Limulus testes cDNA library. The deduced amino acid
      sequence of scruin reflects the domain organization of scruin: it consists of a
      tandem pair of homologous domains joined by a linker region. The domain
      organization of scruin is confirmed by limited proteolysis of the purified
      acrosomal process. Three different proteases cleave the native protein in a 5-kD
      Protease-sensitive region in the middle of the molecule to generate an NH2
      terminal 47-kD and a COOH-terminal 56-kD protease-resistant domains. Although the
      protein sequence of scruin has no homology to any known actin-binding protein, it
      has similarities to several proteins, including four open reading frames of
      unknown function in poxviruses, as well as kelch, a Drosophila protein localized
      to actin-rich ring canals. All proteins that show homologies to scruin are
      characterized by the presence of an approximately 50-amino acid residue motif
      that is repeated between two and seven times. Crystallographic studies reveal
      this motif represents a four beta-stranded fold that is characteristic of the
      "superbarrel" structural fold found in the sialidase family of proteins. These
      results suggest that the two domains of scruin seen in EM reconstructions are
      superbarrel folds, and they present the possibility that other members of this
      family may also bind actin.

PMID- 7822423
TI  - Inhibition of CapZ during myofibrillogenesis alters assembly of actin filaments.
AB  - The actin filaments of myofibrils are highly organized; they are of a uniform
      length and polarity and are situated in the sarcomere in an aligned array. We
      hypothesized that the barbed-end actin-binding protein, CapZ, directs the process
      of actin filament assembly during myofibrillogenesis. We tested this hypothesis
      by inhibiting the actin-binding activity of CapZ in developing myotubes in
      culture using two different methods. First, injection of a monoclonal antibody
      that prevents the interaction of CapZ and actin disrupts the non-striated bundles
      of actin filaments formed during the early stages of myofibril formation in
      skeletal myotubes in culture. The antibody, when injected at concentrations lower
      than that required for disrupting the actin filaments, binds at nascent Z-disks.
      Since the interaction of CapZ and the monoclonal antibody are mutually exclusive,
      this result indicates that CapZ binds nascent Z-disks independent of an
      interaction with actin filaments. In a second approach, expression in myotubes of
      a mutant form of CapZ that does not bind actin results in a delay in the
      appearance of actin in a striated pattern in myofibrils. The organization of
      alpha-actinin at Z-disks also is delayed, but the organization of titin and
      myosin in sarcomeres is not significantly altered. We conclude that the
      interaction of CapZ and actin is important for the organization of actin
      filaments of the sarcomere.

PMID- 7822424
TI  - Drosophila development requires spectrin network formation.
AB  - The head-end associations of spectrin give rise to tetramers and make it possible
      for the molecule to form networks. We analyzed the head-end associations of
      Drosophila spectrin in vitro and in vivo. Immunoprecipitation assays using
      protein fragments synthesized in vitro from recombinant DNA showed that
      interchain binding at the head end was mediated by segment 0-1 of alpha-spectrin
      and segment 18 of beta-spectrin. Point mutations equivalent to erythroid spectrin
      mutations that are responsible for human hemolytic anemias diminished Drosophila
      spectrin head-end interchain binding in vitro. To test the in vivo consequence of
      deficient head-end interchain binding, we introduced constructs expressing head
      end interchain binding mutant alpha-spectrin into the Drosophila genome and
      tested for rescue of an alpha-spectrin null mutation. An alpha-spectrin minigene
      lacking the codons for head-end interchain binding failed to rescue the lethality
      of the null mutant, whereas a minigene with a point mutation in these codons
      overcame the lethality of the null mutant in a temperature-dependent manner. The
      rescued flies were viable and fertile at 25 degrees C, but they became sterile
      because of defects in oogenesis when shifted to 29 degrees C. At 29 degrees C,
      egg chamber tissue disruption and cell shape changes were evident, even though
      the mutant spectrin remained stably associated with cell membranes. Our results
      show that spectrin's capacity to form a network is a crucial aspect of its
      function in nonerythroid cells.

PMID- 7822425
TI  - The anatomy of flagellar microtubules: polarity, seam, junctions, and lattice.
AB  - Although the overall structures of flagellar and cytoplasmic microtubules are
      understood, many details have remained a matter of debate. In particular, studies
      of the arrangement of tubulin subunits have been hampered by the low contrast of
      the tubulin subunits. This problem can now be addressed by the kinesin decoration
      technique. We have shown previously that the recombinant kinesin head domain
      binds to beta-tubulin, thus enhancing the contrast between alpha- and beta
      tubulin in the electron microscope; this allows one to study the arrangement of
      tubulin dimers. Here we describe the lattices of the four different types of
      microtubules in eukaryotic flagellar axonemes (outer doublet A and B, central
      pair C1 and C2). They could all be labeled with kinesin head with an 8-nm axial
      periodicity (the tubulin dimer repeat), and all of them showed the B-surface
      lattice. This lattice is characterized by a 0.92-nm stagger between adjacent
      protofilaments. The B-lattice was observed on the axonemal microtubules as well
      as on extensions made by polymerizing porcine brain tubulin onto axonemal
      microtubules in the proximal and distal directions. This emphasizes that axonemal
      microtubules serve as high fidelity templates for seeding microtubules. The
      presence of a B-lattice implies that there must be a helical discontinuity
      ("seam") in the wall. This discontinuity is now placed near protofilaments A1 and
      A2 of the A-tubule, close to the inner junction between A- and B-microtubules.
      The two junctions differ in structure: the protofilaments of the inner junction
      (A1-B10) are staggered roughly by half a dimer, those of the outer junction (A10
      B1) are roughly in register. Of the two junctions the inner one appears to have
      the stronger bonds, whereas the outer one is more labile and opens up easily,
      generating "composite sheets" with chevron patterns from which the polarity can
      be deduced (arrow in the plus direction). Decorated microtubules have a clear
      polarity. We find that all flagellar microtubules have the same polarities. The
      orientation of the dimers is such that the plus end terminates with a crown of
      alpha subunits, the minus end terminates with beta subunits which thus could be
      in contact with gamma-tubulin at the nucleation centers.

PMID- 7822426
TI  - Identification and partial characterization of mitotic centromere-associated
      kinesin, a kinesin-related protein that associates with centromeres during
      mitosis.
AB  - Using antipeptide antibodies to conserved regions of the kinesin motor domain, we
      cloned a kinesin-related protein that associates with the centromere region of
      mitotic chromosomes. We call the protein MCAK, for mitotic centromere-associated
      kinesin. MCAK appears concentrated on centromeres at prophase and persists until
      telophase, after which time the localization disperses. It is found throughout
      the centromere region and between the kinetochore plates of isolated mitotic CHO
      chromosomes, in contrast to two other kinetochore-associated microtubule motors:
      cytoplasmic dynein and CENP-E (Yen et al., 1992), which are closer to the outer
      surface of the kinetochore plates. Sequence analysis shows MCAK to be a kinesin
      related protein with the motor domain located in the center of the protein. It is
      60-70% similar to kif2, a kinesin-related protein originally cloned from mouse
      brain with a centrally located motor domain (Aizawa et al., 1992). MCAK protein
      is present in interphase and mitotic CHO cells and is transcribed as a single 3.4
      kb message.

PMID- 7822427
TI  - Inhibition of ATP-sensitive potassium channels causes reversible cell-cycle
      arrest of human breast cancer cells in tissue culture.
AB  - The purpose of this study was to determine if potassium channel activity is
      required for the proliferation of MCF-7 human mammary carcinoma cells. We
      examined the sensitivities of proliferation and progress through the cell cycle
      to each of nine potassium channel antagonists. Five of the potassium channel
      antagonists produced a concentration-dependent inhibition of cell proliferation
      with no evidence of cytotoxicity following a 3-day or 5-day exposure to drug. The
      IC50 values for these five drugs, quinidine (25 microM), glibenclamide (50
      microM), linogliride (770 microM), 4-aminopyridine (1.6 mM), and
      tetraethylammonium (5.8 mM) were estimated from their respective concentration
      response curves. Four other potassium channel blockers were tested at supra
      maximal channel blocking concentrations, including charybdotoxin (200 nM),
      iberiotoxin (100 nM), margatoxin (10 nM), and apamin (500 nM), and they had no
      effect on MCF-7 cell proliferation, viability, or cell cycle distribution. Of the
      five drugs that inhibited proliferation, only quinidine, glibenclamide, and
      linogliride also affected the cell cycle distribution. Cell populations exposed
      to each of these drugs for 3 days showed a statistically significant accumulation
      in G0/G1 phase and a significant proportional reduction in S phase and G2/M phase
      cells. The inhibition of cell proliferation correlated significantly with the
      extent of cell accumulation in G0/G1 phase and the threshold concentrations for
      inhibition of growth and G0/G1 arrest were similar. The G0/G1 arrest produced by
      quinidine and glibenclamide were reversed by removing the drug, and cells
      released from arrest entered S phase synchronously with a lag period of
      approximately 24 hours. Based on the differential sensitivity of cell
      proliferation and cell cycle progression to the nine potassium channel
      antagonists, we conclude that inhibition of ATP-sensitive potassium channels in
      these human mammary carcinoma cells, reversibly arrests the cells in the G0/G1
      phase of the cell cycle, resulting in an inhibition of cell proliferation.

PMID- 7822428
TI  - 1,25-Dihydroxyvitamin D3 stimulates the phosphorylation of two acidic membrane
      proteins of 42,000 and 48,000 daltons in rat colonocytes: an effect modulated by
      vitamin D status.
AB  - Our laboratory has recently demonstrated that 1,25-dihydroxyvitamin
      D3(1,25(OH)2D3) rapidly stimulated membrane polyphosphoinositide breakdown and
      increased intracellular calcium, as well as activated protein kinase C (PKC) in
      vitamin D-sufficient rat colonocytes. These effects of 1,25(OH)2D3 were, however,
      lost in vitamin D-insufficient rats and restored by the in vivo repletion of
      1,25(OH)2D3. In the present studies we have examined the ability of 1,25(OH)2D3
      to stimulate the phosphorylation of colonic membrane proteins in intact D
      sufficient cells. In addition, we investigated the effects of vitamin D status on
      the phosphorylation of these membrane proteins in broken cell preparations. These
      studies demonstrated that 1,25(OH)2D3 increased the phosphorylation of at least
      two colonic membrane proteins with apparent molecular weights of 42,000 (pp42)
      and 48,000 (pp48) in intact cells of vitamin D-sufficient rats. Moreover, in
      vitamin D-sufficient rats, treatment of colonocytes with 1,25(OH)2D3 or 12-O
      tetradecanoyl phorbol 13-acetate (TPA), a known activator of PKC, significantly
      increased the phosphorylation of pp42 and pp48 in broken cell preparations. The
      kinetics of these phosphorylations in response to 1,25(OH)2D3 were both rapid and
      transient. In addition, PKC19-36, a specific PKC inhibitor, decreased the
      phosphorylation of pp42 and pp48, whereas okadaic acid (OA), a type 1 and 2A
      protein phosphatase inhibitor, further augmented their phosphorylation in
      response to 1,25(OH)2D3. The isoelectric points of pp42 and pp48 were 5.79 and
      5.97, respectively, and both were predominantly phosphorylated on threonine
      residues. In contrast to our findings in colonocytes from vitamin D-sufficient
      animals, basal phosphorylation of pp42 and pp48 were increased in membranes
      prepared from vitamin D-insufficient rats. Moreover, these phosphorylations
      failed to change in response to 1,25(OH)2D3-treatment of colonocytes from vitamin
      D-insufficient rats. The basal phosphorylation of each of these proteins was
      restored to control levels, as was their ability to respond to the direct
      addition of 1,25(OH)2D3 following the in vivo repletion of vitamin D-insufficient
      rats with this secosteroid. In summary, we have identified two acidic membrane
      proteins from rat colonocytes that are phosphorylated in both intact and broken
      cell preparations in response to 1,25(OH)2D3 treatment, an event modulated by
      vitamin D status and mediated, at least in part, by PKC.

PMID- 7822429
TI  - Iron transport mechanisms in reticulocytes and mature erythrocytes.
AB  - The mechanism of iron transport into erythroid cells was investigated using
      rabbit reticulocytes and mature erythrocytes incubated with 59Fe-labelled Fe(II)
      in isotonic sucrose or in solutions in which the sucrose was replaced with
      varying amounts of isotonic NaCl or KCl. Iron uptake was inhibited at all
      concentrations of NaCl, in a concentration-dependent manner, but with KCl
      inhibition occurred only at concentrations up to 10 mM. Higher KCl concentrations
      stimulated iron uptake to the cytosol of the cells, but inhibited its
      incorporation into heme. This effect became more marked as the iron concentration
      was raised. It was found that KCl inhibits iron incorporation into heme and
      stimulates iron uptake by mature erythrocytes, as well as by reticulocytes. It is
      concluded that erythroid cells can take up nontransferrin-bound Fe(II) by two
      mechanisms. One is a high-affinity mechanism that is limited to reticulocytes,
      saturates at a low iron concentration, and is inhibited by metabolic inhibitors.
      The other is a low-affinity process that is found in both reticulocytes and
      erythrocytes, becomes more prominent at higher iron concentrations, and is
      stimulated by KCl, as well as RbCl, LiCl, CsCl, and choline Cl. The KCl
      stimulation is inhibited by amiloride, but not by metabolic inhibitors, and its
      operation is not dependent on changes in cell volume or membrane potential, but
      it does require the presence of a permeant extracellular anion. Iron uptake by
      this process appears to occur by facilitated transport and is possibly associated
      with exchange of Na+. A further aspect of this study was a comparison of iron
      uptake by reticulocytes from Fe(II)-sucrose and Fe(II)-ascorbate using a variety
      of incubation conditions. No major differences were observed.

PMID- 7822430
TI  - Effects of glucose supply on myeloma growth and metabolism in chemostat culture.
AB  - The effects of the glucose supply on growth and metabolism of an SP2/0 derived
      recombinant myeloma cell line were studied in chemostat culture during growth on
      IMDM medium at a fixed dilution rate of 0.032 h-1. Lowering of the feed medium
      glucose concentration from 25.0 to 1.4 mmol/L resulted in a decrease of steady
      state viable cell concentration from 1.9 x 10(9) to 1.0 x 10(9) L-1, whereas
      viability remained above 90%. Mass balances indicated that only a minor amount of
      glucose was utilized via the TCA cycle irrespective of the glucose concentration
      in the feed medium. The apparent biosynthetic yield of cells from ATP was
      independent of the ratio between the specific glucose and glutamine consumption
      rate. It is concluded that the primary role of glucose is the provision of
      intermediates for anabolic reactions. In addition, glucose may play an indirect
      catabolic role in the process of glutaminolysis by providing the pyruvate for the
      transamination of glutamate to alanine and alpha-ketoglutarate. At low glucose
      concentrations in the feed medium, glutamine is probably the sole energy source
      for this myeloma in chemostat culture.

PMID- 7822432
TI  - Role of ascorbic acid in procollagen expression and secretion by human intestinal
      smooth muscle cells.
AB  - The role of ascorbate in the production and secretion of procollagen by human
      intestinal smooth muscle cells and the conditions in culture for optimal
      ascorbate bioefficacy were studied. Procollagen synthesis and secretion were
      determined by the incubation of cells with L-[5-3H]proline, and the quantitation
      of radiolabelled procollagen bands in the cell layer and the culture medium by
      polyacrylamide slab gel electrophoresis and densitometry. When cells were
      cultured without ascorbate in the culture medium, procollagen secretion into the
      medium was 75% less than in cells receiving fresh ascorbate daily. In the cell
      layer, in contrast, procollagen accumulation was fourfold greater in the
      scorbutic cells than in the ascorbate-replete cells. These findings contrasted
      with those in a control line of scorbutic human dermal fibroblasts in which a 95%
      decrease in procollagen secretion was not associated with any procollagen
      accumulation in the cells. In the intestinal smooth muscle cells, the absence of
      ascorbate resulted in a 25 and 50% decrease in steady-state levels of procollagen
      I and III mRNA, respectively, compared to a 40 and 75% decrease in fibroblasts.
      Heat inactivation of the serum in the culture medium augmented the promotion of
      procollagen secretion by ascorbate two- to fourfold. L-ascorbate phosphate did
      not increase the activity of L-ascorbate when replaced in medium either daily or
      every 4 days, and its efficacy was not augmented by serum heat inactivation. The
      changing of culture medium induced collagen secretion in the absence of
      ascorbate, but this process was markedly enhanced by ascorbate and induced a
      transient decrease in the steady-state levels of both procollagen and
      nonprocollagen mRNAs. The predominant action of L-ascorbate on HISM cells in
      vitro is to promote procollagen secretion and not procollagen synthesis. L
      ascorbate-phosphate is not an adequate substitute for L-ascorbate in this cell
      line.

PMID- 7822431
TI  - Expression of tissue-type plasminogen activator and its inhibitor couples with
      development of capillary network by human microvascular endothelial cells on
      Matrigel.
AB  - Human omental microvascular endothelial (HOME) cells seeded on Matrigel begin to
      migrate within 1 h, forming honeycomb-like structures and capillary-like networks
      within 18 h. Cross-sections of the capillary networks show them to be tube-like
      structures. Northern blot analysis showed that tissue-type plasminogen activator
      (t-PA) mRNA synthesis increased from the initial state at 0 h after seeding on
      Matrigel, reaching a steady state after 4 h. This elevated cellular t-PA mRNA
      level decreased markedly at 24 h. In contrast, the cellular plasminogen activator
      inhibitor-1 (PAI-1) mRNA level demonstrated biphasic curves during the 24 h after
      seeding on Matrigel: the PAI-1 mRNA level was increased eightfold initially at 4
      h over that at 0 h, then declined, and again secondarily increased to greater
      than tenfold at 18 h. Cellular levels of both 72 kD type IV collagenase and
      tissue inhibitor of metalloproteinase (TIMP-2) mRNA were increased only a
      slightly within 2-4 h. These elevated mRNA levels were maintained for 18 h, while
      the TIMP-1 mRNA level increased up to 18 h, reaching around three times the level
      at 0 h. However, on collagen-coated dishes, cellular levels of t-PA, PAI-1, 72 kD
      type IV collagenase, TIMP-1, and TIMP-2 mRNA were not greatly changed during
      incubation for 24 h. On Matrigel, the cellular t-PA mRNA level at 18 h after
      seeding was greatly increased when treated with specific anti-transforming growth
      factor-beta (TGF-beta) antibody. In contrast, both PAI-1 and TIMP-1 mRNA levels
      at 18 h were reduced in the presence of anti-TGF-beta antibody. Development of
      the capillary network on Matrigel was inhibited in the presence of anti-t-PA
      antibody. Epidermal growth factor (EGF) enhanced t-PA gene expression and TGF
      beta inhibited its expression in HOME cells cultured on collagen-coated dishes.
      On the other hand, TGF-beta enhanced cellular expression of the PAI-1 gene. The
      formation of a capillary network by HOME cells on Matrigel appears to be balanced
      by angiogenic EGF and anti-angiogenic TGF-beta through modulation of PA activity.

PMID- 7822433
TI  - Regulation of human ornithine decarboxylase expression following prolonged
      quiescence: role for the c-Myc/Max protein complex.
AB  - WI-38 cells can remain quiescent for long periods of time and still be induced to
      reenter the cell cycle by the addition of fresh serum. However, the longer these
      cells remain growth arrested, the more time they require to enter S phase. This
      prolongation of the prereplicative phase has been localized to a point early in
      G1, after the induction of "immediate early" G1 genes such as c-fos and c-jun but
      before maximal expression of "early" G1 genes such as ornithine decarboxylase
      (ODC). Understanding the molecular basis for ODC mRNA induction can therefore
      provide information about the molecular events which regulate the progression of
      cells out of long-term quiescence into G1 and subsequently into DNA synthesis.
      Studies utilizing electrophoretic mobility shift assays (EMSA) of nuclear
      extracts from short- and long-term quiescent WI-38 cells identified a region of
      the human ODC promoter at -491 bp to -474 bp which exhibited a protein binding
      pattern that correlated with the temporal pattern of ODC mRNA expression. The
      presence of a CACGTG element within this fragment, studies with antibodies
      against c-Myc and Max, the use of purified recombinant c-Myc protein in the
      mobility shift assay, and antisense studies suggest that these proteins can
      specifically bind this portion of the human ODC promoter in a manner consistent
      with growth-associated modulation of the expression of ODC and other early G1
      genes following prolonged quiescence. These studies suggest a role for the c
      Myc/Max protein complex in regulating events involved in the progression of cells
      out of long-term quiescence into G1 and subsequently into S.

PMID- 7822434
TI  - Regulation of autocrine gastrin expression by the TGF alpha autocrine loop.
AB  - Gastrin is transcriptionally responsive to EGF stimulation (Merchant et al.,
      1991, Mol. Cell. Biol., 11:2686-2696). Consequently, we hypothesized that
      previously recognized gastrin autocrine loops (Hoosein et al., 1990, Exp. Cell.
      Res., 186:15-21), might be controlled by autocrine TGF alpha in human colon
      carcinoma cells. Therefore, we examined the interaction between these two
      autocrine growth factors in two colon carcinoma cell lines which utilize TGF
      alpha. The FET cell line requires exogenous TGF alpha/EGF for optimal growth and
      has a classical TGF alpha autocrine loop which is disrupted by TGF alpha or
      epidermal growth factor receptor (EGFr) antibodies. The HCT 116 cell line is not
      dependent on exogenous TGF alpha/EGF and exhibits a nonclassical TGF alpha
      autocrine loop which is not disrupted by neutralizing antibodies to either TGF
      alpha itself or the EGFr. Basal gastrin mRNA production is significantly higher
      in HCT 116 than FET as measured by RNase protection assay. In the FET cells,
      exogenous EGF stimulates gastrin mRNA production but not in HCT 116. When the TGF
      alpha autocrine loop in HCT 116 is disrupted by constitutive expression of
      antisense TGF alpha mRNA, the gastrin mRNA level is significantly repressed. In
      xenografts derived from these antisense clones, TGF alpha reverted to high
      expression, and the gastrin mRNA level was again increased. This interaction
      between the strong TGF alpha loop in HCT 116 and the gastrin autocrine loop may
      confer a growth advantage to these colon cells. Such interactions between growth
      factors may promote enhanced tumorigenicity to transformed cells with these
      strong, nonclassical autocrine loops.

PMID- 7822435
TI  - Regulation of c-fos expression in senescing Werner syndrome fibroblasts differs
      from that observed in senescing fibroblasts from normal donors.
AB  - The Werner syndrome (WS) is a segmental progeroid syndrome caused by a recessive
      mutation (WRN) mapped to 8p12. The replicative life spans of somatic cells
      cultured from WS patients are substantially reduced compared to age-matched
      controls. Certain molecular concomitants of the replicative decline of normal
      fibroblast cultures have recently been defined, and it appears that multiple
      changes in gene expression accompany normal cell senescence. If the mechanisms by
      which WS cells exit the cell cycle were entirely comparable, the molecular
      markers of senescence should be identical in normal and WS cells. We find that
      this is not the case. The constitutive expression of statin, a nuclear protein
      associated with the nonproliferating state, was comparably expressed in normal
      and WS senescent cells. Likewise, the steady state levels of p53, a protein known
      to be involved in the G1 checkpoint of the cell cycle, were similar in early
      passage fibroblasts from normal and WS subjects. The levels of p53 were not
      increased in senescent fibroblasts, whether derived from normal or WS subjects.
      By contrast, the inducibility of mRNA and protein expression of the c-fos
      protooncogene is preserved in late-passage WS cells. This is in contrast to what
      is observed in late-passage fibroblasts from normal subjects. Additional
      genotypes will have to be examined, however, to determine the specificity of this
      new aspect of the WS phenotype.

PMID- 7822436
TI  - Kinetics of myo-inositol transport in rat ocular lens.
AB  - Myo-inositol (MI) influx as a function of concentration in rat lens consisted of
      a saturable component, fit by a rectangular hyperbola, and a linear component
      which was more distinct at high myo-inositol concentrations suggesting passive
      diffusion. The hyperbolic component was half-maximally saturated (Kt) at 61.3
      microM and had a maximal transport rate (Jmax) of 44.6 mumol/kg wet wt/h. The
      linear component had an apparent permeability coefficient of 1.44 x 10(-6) s-1.
      Sorbitol, which distributed rapidly in the extracellular space (6.83 ml/100 g wet
      wt), also appeared to enter the intracellular space with a permeability
      coefficient of 1.37 x 10(-6) s-1, similar to that of myo-inositol. The influx of
      myo-inositol was critically dependent on the concentration of extracellular
      sodium consistent with a sodium-myo-inositol cotransport. The kinetics of influx
      activation by sodium suggested an apparent 2:1 coupling ratio for sodium and myo
      inositol. When potassium was used as sodium substitute, a significantly stronger
      influx inhibition was observed than with nondepolarizing sodium substitutes,
      indicating that myo-inositol was driven by the electrochemical gradient of sodium
      rather than the chemical gradient only. Reducing the extracellular Na
      concentration increased the MI concentration at which transport was half
      maximally activated, suggesting an ordered binding sequence of Na followed by MI.
      Myo-inositol influx was competitively inhibited by phlorizin with an inhibitory
      coefficient (Ki) of 35 microM. Phloretin also was capable of inhibition but with
      a much lesser efficacy. Myo-inositol desaturates from the lens at a rate of
      0.00862 h-1. Approximately 19% of the efflux can be inhibited with phlorizin,
      suggesting that it represents carrier-mediated flux. The phlorizin insensitive
      flux has a rate of 0.00695 h-1 or 1.93 x 10(-6) s-1, similar to the Na
      independent passive influx. MI influx is due to a Na-dependent, phlorizin
      sensitive active transport while the efflux consists largely of a phlorizin
      independent passive leakage.

PMID- 7822437
TI  - Influence of age, sex, and dietary restriction on intracellular free calcium
      responses of CD4+ lymphocytes in rhesus monkeys (Macaca mulatta).
AB  - The influence of aging and dietary restriction on increase in intracellular free
      calcium ([Ca2+]i) of CD4+ lymphocytes from Macaca mulatta was examined after
      stimulation with anti-CD3 mAb. We used a flow cytometric assay with the dye indo
      1 and either direct or reciprocal immunofluorescent staining to identify CD4+
      cells. After stimulation with anti-CD3 mAb, intracellular free calcium responses
      were reduced in CD4+ lymphocytes from old male and female ad libitum fed monkeys
      compared to young and adult male or female monkeys. Old female monkeys had
      significantly lower [Ca2+]i than did old male monkeys. The reduced responses were
      in part related to a decreased percentage of responding cells. Dietary
      restriction of males over a four-year period did not alter [Ca2+]i response
      compared to ad libitum fed male monkeys. Female monkeys of all ages (which were
      restricted only for four months) also had similar [Ca2+]i responses to ad libitum
      fed controls. Our data suggest that age-related changes in [Ca2+]i responses are
      similar between humans and M. mulatta, and that over these intervals, no effects
      of caloric restrictions can be detected.

PMID- 7822438
TI  - Open sesame, goodbye calcium.

PMID- 7822439
TI  - Case in point. Ovarian carcinoma mimicking ascites.

PMID- 7822440
TI  - Heaven, Hell, and bioenergetics.

PMID- 7822441
TI  - Heart failure, supraventricular tachycardia, and cardiomyopathy.

PMID- 7822442
TI  - Case in point. Madura foot (mycetoma).

PMID- 7822443
TI  - Gastric adenocarcinoma: where are we headed?
AB  - In Japan, screening for gastric cancer is cost-effective, and intervention in
      advanced disease often includes radical lymphadenectomy. Such strategies may be
      applicable elsewhere, along with nonsurgical management strategies, especially if
      ways can be found to focus screening on high-risk groups.

PMID- 7822445
TI  - Annualizing our approach to influenza.

PMID- 7822444
TI  - Management decisions in subclinical thyroid disease.
AB  - Subclinical hypo- and hyperthyroidism are common, well-defined conditions that
      often progress to overt disease. In addition, there have been concerns that the
      subclinical states may contribute to hyperlipidemia, cardiac dysfunction, and
      osteoporosis. The author discusses the issues and outlines a rational approach to
      management that identifies patients who will benefit from treatment.

PMID- 7822446
TI  - Taking on a computer partner.

PMID- 7822447
TI  - Leg pain and numbness in an elderly man.

PMID- 7822448
TI  - Pregnancy in diabetes: reducing the risks.
AB  - Meticulous glucose control that begins long before conception is fundamental to
      protecting the fetus and mother. Maternal hypertension, retinopathy, renal
      disease, and neuropathy may lead to complications, but optimal education, care,
      and fetal monitoring can reduce the risks.

PMID- 7822449
TI  - Diagnosis and treatment of Parkinson's disease.
AB  - At its inception, the disease may be among the hardest neurologic disorders to
      recognize. Other problems may arise later, both from the disease and from its
      treatment. Indeed, adverse drug effects range from orthostatic hypotension to
      drug-induced dyskinesias and psychiatric disorders. For many such difficulties,
      clinical experience can offer practical suggestions.

PMID- 7822450
TI  - Health care reform is dead, long live health care reform?

PMID- 7822451
TI  - Robert Koch and the modern investigator.

PMID- 7822452
TI  - Detection of hepatitis A, B and D virus by the polymerase chain reaction.

PMID- 7822453
TI  - The packaging signal in hepatitis B virus pregenome functions only at the 5' end.
AB  - When the hepatitis B virus (HBV) replicates, a full-size transcript of the viral
      genome, called pregenome RNA, is made and is selectively packaged into virus core
      particles. This selective encapsidation is dependent upon the presence of a
      specific cis-acting sequence called the packaging signal that is found at the 5'
      end of the pregenome RNA. Deletion analysis revealed that this packaging signal
      was located in a 70 bp stretch of nucleotides. Packaging defective virus genome
      containing the 70 bp packaging signal sequence at several locations, showed that
      the packaging occurs effectively only when the signal is located near the 5' end
      of the pregenome RNA. Packaging also occurred with a 2.4 kb viral RNA whose 5'
      region sequence was different from that of the pregenome RNA, but which has the
      packaging signal sequence inserted at the 5' region.

PMID- 7822454
TI  - Typing of human papillomaviruses by consensus polymerase chain reaction and a non
      radioactive reverse dot blot hybridization.
AB  - A non-radioactive reverse dot blot hybridization method was developed for typing
      of human papillomavirus (HPV) consensus primer generated polymerase chain
      reaction (PCR) products in a single test. In the PCR biotin-14-dATP was
      incorporated into the amplified DNA, which was then used as a probe in
      hybridization with a membrane, on which different genital HPV types had been
      immobilized. Of cervical brush samples from women referred to a colposcopy clinic
      (n = 58) and from women attending a health control program (n = 14) which had
      been found positive by PCR with consensus HPV primers but negative using primers
      specific for the HPV types 6, 11, 16, 18, 31, 33 and 35, 25 (43%) and 3 (21%),
      respectively, could be typed by this method. The additional HPV types found were
      34, 39, 40, 45, 52, 53, 56 and 58. Of the samples from the colposcopy clinic (n =
      33) and the health control group (n = 11) which could not be typed, 23 and 5,
      respectively, showed HPV X which cross-hybridized with various HPV types under
      conditions of low stringency. It is possible to type by this fast and easy method
      consensus primer-generated PCR products of a wide range of HPV types or to verify
      the presence of HPV DNA of unknown types.

PMID- 7822455
TI  - Quantitative detection of hepatitis B virus DNA in serum using chemiluminescence:
      comparison with radioactive solution hybridization assay.
AB  - A quantitative, non-radioactive hybrid capture HBV DNA assay (Digene
      Diagnostics), which uses an efficient solution hybridization procedure coupled to
      a sensitive chemiluminescent signal amplification system, was compared with the
      quantitative, radioactive solution hybridization assay (Genostics, Abbott
      Laboratories), in hepatitis B virus carriers, particularly in those undergoing
      antiviral therapy. The qualitative reproducibility of the chemiluminescent
      method, tested on 30 sera, was acceptable, with a reproducibility rate of 93.3%.
      A comparison of this hybrid capture HBV DNA assay with the radioactive test on
      113 sera obtained from 48 patients (39 HBsAg-positive patients) gave a
      sensitivity of 87.2%, a specificity of 100% and an agreement between the two
      tests of 89.4% (101 sera including 82 HBV DNA positive and 19 negative samples).
      Changes in HBV DNA levels measured by the two assays showed a good correlation
      with each other during interferon therapy. However, the hybrid capture values
      were higher than the radioactive assay values, with the ratio of the two values
      being variable in the same patient during the course of treatment. The Genostics
      assay therefore seems to be a more accurate procedure for evaluating changes in
      viral replication, particularly at high HBV DNA levels. However, the hybrid
      capture method is faster and has the advantage of being a non-radioactive
      procedure. This chemiluminescent assay is easy to perform as a routine diagnostic
      procedure and may be a useful alternative to the radioactive solution
      hybridization method.

PMID- 7822456
TI  - An efficient and easy method of infection of mosquito larvae from virus
      contaminated cell cultures.
AB  - A new method for efficient infection of Aedes aegypti larvae by the Aedes
      albopictus densovirus, AaPV is described. It consists of placing first or third
      instar larvae in culture flasks containing a chronically infected mosquito cell
      line. After 24 or 48 h of exposure to the contaminated culture, the larvae
      acquired the virus by feeding on infected cells. Using this technique, up to 95%
      of first instar Ae. aegypti larvae were found infected by the AaPV.

PMID- 7822458
TI  - A sensitive assay system screening antiviral compounds against herpes simplex
      virus type 1 and type 2.
AB  - A highly sensitive and accurate assay system was developed for in vitro
      evaluation of anti-herpes simplex virus (anti-HSV) agents using 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and human embryonic
      lung fibroblast (MRC-5) cells. This assay system was found to be highly sensitive
      for both HSV-1 and -2. Confluent MRC-5 cells were infected with either HSV-1 KOS
      strain or HSV-2 G strain of 25 TCID50 in the presence of various concentrations
      of test compounds. The optical density of formazan was used to determine cell
      viability. The EC50 values of acyclovir and several other anti-HSV agents were
      found to be similar to those obtained by the plaque reduction method. These
      results indicate that this MTT assay is useful for screening anti-HSV-1 and -2
      agents.

PMID- 7822457
TI  - A one-tube quantitative HIV-1 RNA NASBA nucleic acid amplification assay using
      electrochemiluminescent (ECL) labelled probes.
AB  - Quantification of HIV-1 viral RNA based on co-amplification of an internal
      standard Q-RNA dilution series requires a number of NASBA nucleic acid
      amplification reactions. For each internal standard Q-RNA concentration a
      separate NASBA amplification has to be performed. The development of an
      electrochemiluminescent (ECL) detection system with a dynamic signal detection
      range over 5 orders of magnitude enabled simplification of the Q-NASBA protocol.
      Three distinguishable Q-RNAs (QA, QB and QC) are mixed with the wild-type sample
      at different amounts (i.e. 10(4) QA, 10(3) QB and 10(2) QC molecules) and co
      amplified with the wild-type RNA in one tube. Using ECL-labelled oligonucleotides
      the wild-type, QA, QB and QC amplificates are separately detected with a semi
      automated ECL detection instrument and the ratio of the signals determined. The
      amount of initial wild-type RNA can be calculated from the ratio of wild-type
      signal to QA, QB and QC signals. This one-tube Q-NASBA protocol was compared to
      the earlier described protocol with six amplifications per quantification using
      model systems and HIV-1 RNA isolated from plasma of HIV-1-infected individuals.
      In all cases the quantification results of HIV-1 RNA were comparable between the
      two methods tested. Due to the use of only one amplification per quantification
      in the one-tube Q-NASBA protocol the QA, QB and QC internal standard RNA
      molecules can be added to the sample before nucleic acid isolation. The ratio of
      QA:QB:QC:WT RNAs, from which the initial input of WT-RNA is calculated, will
      remain constant independent of any loss that might occur during the nucleic acid
      isolation.

PMID- 7822459
TI  - Improved detection of persistent foot-and-mouth disease infection in cattle by
      the polymerase chain reaction.
AB  - Persistent foot-and-mouth disease (FMD) infection of cattle was established by
      exposure to infected pigs. Oesophageal-pharyngeal fluid samples collected ante
      mortem and tissue samples obtained post-mortem were tested for virus by
      conventional means and for viral RNA by the polymerase chain reaction (PCR). The
      results showed that the PCR was superior for detecting the carrier state in
      tissue samples. A high neutralising activity in tissues probably influenced the
      yields of virus obtained by infectivity assay.

PMID- 7822460
TI  - Use of non-radioactively labeled DNA probes for the detection of a baculovirus
      from Penaeus monodon by in situ hybridization on fixed tissue.
AB  - Clones isolated from a genomic library of the baculovirus PmSNPV (= MBV) were
      used to prepare DNA probes for detection of PmSNPV in shrimp tissue. Davidson's
      AFA fixed shrimp tissues were probed using DNA that had been labeled with the
      hapten, digoxigenin, by an in situ hybridization assay. The DNA probes readily
      distinguished PmSNPV-infected from uninfected shrimp tissue. The reactions were
      localized to the hepatopancreas and midgut, the sites where this virus is
      detected by standard histological methods. The probes did not react to shrimp
      infected with Baculovirus penaei (BP = PvSNPV).

PMID- 7822461
TI  - Quantitation of human cytomegalovirus DNA in leukocytes by end-point titration
      and duplex polymerase chain reaction.
AB  - The presence of human cytomegalovirus (CMV) DNA and cellular DNA in leukocytes
      was detected by duplex polymerase chain reaction (PCR) and quantitated by end
      point titration. Two different duplex PCR methods were used to co-amplify CMV DNA
      and a 536 bp fragment of globin DNA. MIE-globin PCR amplified a 435 bp fragment
      of the major immediate early (MIE) gene of CMV DNA whereas the LA-globin PCR
      amplified a 200 bp fragment of the late antigen (LA) gene of CMV DNA. PCR
      products were separated by electrophoresis in 3% agarose gels and detected by
      ethidium bromide staining. Amplification of globin DNA was included in the PCR as
      a positive control to monitor the accuracy and reproducibility of the PCR assay
      and to provide a reference point for CMV DNA levels. End-point titration PCR
      using known amounts of recombinant CMV DNA and human placental DNA showed that
      the end-point titres of the amplified CMV DNA correlated directly with the amount
      of CMV DNA in the sample. The limit of detection of MIE-globin and LA-globin PCR
      was 1 ng for placental DNA, and 10 fg (1000 copies) for CMV-MIE DNA and 1 fg (100
      copies) for CMV-LA DNA, respectively. The amount of CMV DNA was quantitated in
      leukocytic lysates of 16 immunocompromised patients, who were tested for the
      presence of CMV in blood by cell culture, and of four normal controls. The blood
      concentration of CMV DNA, calculated as the number of copies of CMV DNA per
      microgram of leukocyte DNA, varied between 10(4) and 10(7) in the seven bloods
      that were CMV-cell-culture-positive, and between 10(2) and 10(4) in the blood of
      five patients that were CMV-cell-culture-negative. CMV DNA was undetected by PCR
      in the blood of another eight CMV-negative cases. This study shows that end-point
      titration and duplex PCR can be used as a simple and rapid method to quantitate
      CMV DNA in blood of patients that are either CMV-positive or CMV-negative by cell
      culture. Quantitation of CMV DNA in blood by end-point titration PCR has
      potential to differentiate between asymptomatic CMV infection and symptomatic CMV
      disease, and to monitor viral load during viral therapy.

PMID- 7822462
TI  - Multimeric non-radioactive cRNA probes improve detection of potato spindle tuber
      viroid (PSTVd).
AB  - Experimental data showed that multimeric, complementary RNA (cRNA) probes,
      labelled with non-radioactive digoxigenin (DIG), improved sensitivity of
      detection of the potato spindle tuber viroid (PSTVd) RNA by 2- to 30-fold as
      compared with corresponding multimeric cDNA probes. The degree of PSTVd
      detectability improvement depended upon the type of alkaline phosphatase
      substrate (colorimetric vs. chemiluminescent) used. Use of hexameric DIG-labelled
      cRNA probes in combination with chemiluminescent (Lumi-Phos 530) substrate
      resulted in detection of 0.48 pg of PSTVd RNA. The size of the synthesized cRNA
      probes corresponded to the size of the respective PSTVd cDNA templates.
      Interestingly, there was no relationship between the size of the synthesized, DIG
      labelled DNA probes and that of the PSTVd cDNA template. This type of anomaly was
      not observed with other plant viral cDNA templates. Monomeric or multimeric cDNA
      probes detected both a mild and a severe PSTVd strain in viroid-infected potato
      leaf extracts diluted 1024 to 2048 times. In comparison, cRNA probes exhibited a
      much greater dilution end point; PSTVd RNA was detectable in viroid-infected
      potato leaf tissue diluted up to 16,384 times. Comparable levels of PSTVd
      sensitivity of detection were obtained with viroid-infected potato tuber tissue.

PMID- 7822463
TI  - Enhancement of infectivity of hantavirus in cell culture by centrifugation.
AB  - Centrifugation was introduced during virus adsorption to Vero E6 cells to improve
      the infectivity of hantavirus. Centrifugal adsorption of a stock solution of
      Hantaan virus strain 76-118 to a monolayer of Vero E6 cells enhanced virus
      infectivity depending on the centrifugation time and the centrifugal force. The
      maximum level of infectivity (3.1 x 10(6) FFU/ml) was enhanced after a 2 h
      centrifugation at 671 x g, which was almost 9-times higher than that of
      conventional adsorption of the virus at 37 degrees C for 1 h. Vero E6 cells were
      inoculated with a new hantavirus strain, KI-91-40, isolated with a low infectious
      titer (400 FFU/ml) from an urban rat and adsorbed by centrifugation. A higher
      virus titer was detected sooner compared to when using conventional adsorption.
      To analyze the mechanism of the enhancement, the centrifugation was carried out
      before and after virus adsorption. The infectivity was reduced when Vero E6
      monolayers were centrifuged before virus inoculation. When the centrifugation
      proceeded after inoculation, the infectivity was almost equal to that without
      centrifugation. The infectivity was only enhanced when centrifugation was carried
      out during inoculation. These results indicate that centrifugation promotes a
      very early event of infection, probably attachment of the virus to cells.

PMID- 7822475
TI  - Adhesion molecule expression and lymphocyte adhesion to cerebral endothelium:
      effects of measles virus and herpes simplex 1 virus.
AB  - Expression of endothelial cell (EC) adhesion molecules is increased in
      inflammatory neurological disorders and this may regulate lymphocyte homing to
      the central nervous system (CNS). Viral encephalitis is characterised by
      lymphocytic infiltration of the CNS and one mechanism of this response may be EC
      adhesion molecule induction with consequent inflammatory cell/EC binding. This
      report characterises the effects of herpes simplex 1 (HSV1) or measles virus (MV)
      infection of BALB/c brain microvascular EC in vitro on adhesion of naive syngenic
      splenocytes and levels of ICAM-1. Adhesion was enhanced by 42% for MV-infected
      cells and by 73% for HSV-1-infected EC. At the multiplicities of infection
      employed, levels of ICAM-1 were upregulated on HSV-1-infected EC, but not on MV
      infected EC. It is concluded that ICAM-1/ligand interactions do not play a role
      in mediation of MV enhancement of adherence, but represent one mechanism
      responsible for increased lymphocyte adherence to HSV-1-infected cerebral EC.

PMID- 7822476
TI  - cAMP accumulation in T-cells inhibits anti-CD3 monoclonal antibody-induced actin
      polymerization.
AB  - The results presented in this report offer a novel explanation for how
      stimulation of the beta-adrenergic receptor (beta AR) inhibits the ability of T
      cells to proliferate after interaction with immobilized anti-CD3 monoclonal
      antibody (mAb). Accordingly, T cells binding to immobilized anti-CD3 mAb but not
      anti-CD4 mAb undergo time-dependent F-actin assembly with concomitant formation
      of pseudopodia. This process is completely inhibited in the presence of
      isoproterenol (ISO) indicating that stimulation of the beta AR on T cells
      interferes with the biochemical processes responsible for the assembly of actin.
      To confirm these observations, we quantitated the formation of F-actin in T cells
      stimulated with immobilized anti-CD3 mAb in the presence of cAMP elevating
      agents. The results show that stimulation of the beta AR on T-cells, as well as
      the addition of forskolin or dibutyryl cAMP, abrogates the formation of F-actin.

PMID- 7822477
TI  - Thrombomodulin in the sera of patients with multiple sclerosis and human
      lymphotropic virus type-1-associated myelopathy.
AB  - Damage to the blood-brain barrier, which mainly consists of cerebral endothelial
      cells, has been demonstrated in multiple sclerosis (MS) clinically and
      histochemically. To investigate the endothelial cell damage, we evaluated the
      presence of soluble thrombomodulin in the sera of patients with MS and human T
      lymphotropic virus type-1-associated myelopathy (HAM) using an enzyme-linked
      immunosorbent assay. Serum thrombomodulin levels were significantly increased in
      patients with acute relapsing MS during an exacerbation and chronic progressive
      MS as compared with those of controls (P < 0.001, respectively). Patients with
      HAM also had higher serum levels of thrombomodulin than did controls (P < 0.001).
      There was significant difference between patients with HAM and seropositive non
      HAM carriers (P < 0.01). These results suggest that the detection of serum
      thrombomodulin could be used as a marker of endothelial cell damage in
      inflammatory diseases such as MS and HAM.

PMID- 7822478
TI  - Human malignant astrocytes express macrophage phenotype.
AB  - Six well-characterized specimens of cultured astrocytoma cells were investigated
      with a panel of macrophage markers. Our results show that the macrophage markers
      OKM-1(CD11b), OKM5(CD36), EBM11(CD68), HAM56, Factor 13, alpha-1
      antichymotrypsin, alpha-1-antitrypsin, ferritin and lysozyme are clearly reactive
      to neoplastic astrocytes whereas astrocytes in normal brain specimens are not
      reactive. In order to obtain further confirmation concerning the reactivity of
      tumor cells in vivo, we simultaneously measured by flow cytometric analysis DNA
      content and HAM56 immunoreactivity in a freshly obtained tumor specimen. In this
      experiment we found a marked reactivity of aneuploid cells to HAM56. The
      macrophage phenotype of malignant astrocytes may reflect a similarity in
      functions of these cells and tumor-associated macrophages which promote tumor
      growth via the production of growth factors and angiogenic factors. Furthermore,
      our findings implicate that demonstration of macrophages within malignant
      astrocytomas by using macrophage-specific antibodies must be cautiously
      considered.

PMID- 7822479
TI  - Presence and isotype of anti-ganglioside antibodies in healthy persons, motor
      neuron disease, peripheral neuropathy, and other diseases of the nervous system.
AB  - Antibodies of the IgM, IgG and IgA class against GM1, asialo-GM1, GD1b and GM2
      gangliosides were determined in the sera of patients with motor neuron disease
      (MND), peripheral neuropathy, other neurological diseases (OND) and healthy
      individuals. Antibodies of the three immunoglobulin classes were present in
      healthy persons. MND patients did not differ from OND or controls in anti-GM1
      titers of the three isotypes. In the group of peripheral neuropathy, no
      elevations of antibody titers were observed in patients with sensory or sensory
      motor neuropathy; however, four out of 12 patients with the motor variety had
      very high levels of IgM or IgG antibodies. Two of these four patients also had
      increased titers of IgA antibodies, but no patients exhibited high titers
      restricted to this isotype.

PMID- 7822480
TI  - Interferon-gamma-inducible genes in primary glial cells of the central nervous
      system: comparisons of astrocytes with microglia and Lewis with brown Norway
      rats.
AB  - We compared the expression of various interferon-gamma (IFN-gamma)-inducible
      mRNAs in primary rat astrocytes and microglia. Of 11 different mRNAs inducible by
      IFN-gamma in a macrophage cell line, RAW 264.7, only eight were induced in both
      types of glia, which included mRNAs encoding the transcriptional factors, IRF-1,
      LRF-1 and ZIF-268; members of the chemokine family, crg-2/IP-10 and MIG; beta 2
      microglobulin and metallothionein-II. The patterns of induction of the mRNAs were
      more similar between astrocytes and microglia than with RAW 264.7 cells.
      Comparison of astrocytes from Lewis and Brown Norway rats showed no major
      differences in the levels of the crg mRNAs or in the amount of Crg-2 protein
      induced by IFN-gamma.

PMID- 7822481
TI  - Stress-induced reduction in the rat mixed lymphocyte reaction is due to
      macrophages and not to changes in T cell phenotypes.
AB  - Exposure to aversive events or stressors modulates various aspects of immune
      function. We have previously reported that exposure to an acute stressor,
      inescapable tail shock (IS), resulted in a shift in T cell subpopulations in rat
      mesenteric lymph nodes but not in cervical lymph nodes (Fleshner et al. (1992) J.
      Neuroimmunol. 41, 131-142). The mesenteric CD4+/CD8+ ratio was increased
      immediately after exposure to IS and was due primarily to an increase in the
      percent of CD4+ cells. The present experiments were designed to determine the
      relationship between the IS-associated phenotypic shift and its significance in
      the function of CD4+ T cells. The function assessed was the in vitro
      proliferative response to alloantigens coded for by the Major Histocompatibility
      Complex (MHC). Using the mixed lymphocyte reaction (MLR), we report that exposure
      to IS resulted in a decrease in the MLR response of cells from both cervical and
      mesenteric lymph nodes. Depletion of macrophages (nylon wool adherent cells)
      eliminated the IS-induced reduction and co-culture of macrophages (irradiation
      insensitive cells) from shocked rats produced the suppression. One interpretation
      of these data is that exposure to IS resulted in the activation of macrophages
      and the release of a suppressive factor which reduced the MLR response of
      peripheral lymph node lymphocytes.

PMID- 7822482
TI  - Expression of vimentin increases in the hippocampus and cerebral cortex after
      entorhinal cortex lesioning and in response to transforming growth factor beta 1.
AB  - Entorhinal cortex lesions (ECL) that damage the perforant path to the dentate
      gyrus of the hippocampal formation were used to model the regulation of vimentin
      (VIM) mRNA. ECL increased VIM mRNA in the ipsilateral hippocampus and in the
      ipsilateral cortex including the wound cavity within 1 day. By in situ
      hybridization, at 4 days post-ECL, VIM mRNA increased two-fold in the molecular
      layer of the dentate gyrus. VIM protein was co-localized by immunocytochemistry
      to astrocytes and microglia/macrophages. Transforming growth factor-beta 1 (TGF
      beta 1), which was previously shown to increase in microglia/macrophages of the
      molecular layer after hippocampal deafferentation by ECL, was investigated as a
      regulator of VIM expression. Infusions of TGF-beta 1 into the lateral ventricle
      induced VIM mRNA with dose-dependence, e.g. infusion of 100 ng TGF-beta 1
      increased VIM mRNA three-fold. The increase in VIM mRNA was localized by in situ
      hybridization to astrocytes and microglia in the molecular layer of the dentate
      gyrus. These findings further implicate TGF-beta 1 as a regulator of cytoskeletal
      proteins during synaptic reorganization.

PMID- 7822483
TI  - Antigen presentation by thymoma epithelial cells from myasthenia gravis patients
      to potentially pathogenic T cells.
AB  - Thymomas associate strongly with myasthenia gravis (MG). We now show that
      cultured thymoma epithelial cells can present synthetic acetylcholine receptor
      (AChR) peptides to HLA-sharing responder T cell lines/clones nearly as
      efficiently as blood mononuclear cells. Responses depended strictly on the
      specific antigen added. Processing of longer recombinant AChR polypeptides was
      clearly less efficient than by blood mononuclear cells, and was selectively
      abolished by preculture with chloroquine. The T cell responses depended on the
      presence of LFA-3 on the thymoma cells. This study demonstrates that thymoma
      epithelial cells have the capacity to stimulate T cells and perhaps, therefore,
      to autosensitize against AChR in vivo.

PMID- 7822484
TI  - Differential activation of adrenal steroid receptors in neural and immune tissues
      of Sprague Dawley, Fischer 344, and Lewis rats.
AB  - Sprague Dawley (SD), Fischer 344 (F344), and Lewis (LEW) rats are used in a wide
      variety of laboratory studies. Compared to SD and LEW rats, F344 rats show
      significantly greater corticosterone secretion in response to stress, or to
      immune challenge. These strain differences in hypothalamic-pituitary-adrenal
      (HPA) axis responsivity have been the basis for many comparative studies
      investigating immunological and behavioural differences between the three
      strains. However, the effects of these strain differences in HPA axis
      responsivity have not been investigated at the level of adrenal steroid receptor
      activation in target tissues. The present study demonstrates that compared to SD
      and LEW rats, F344 rats exhibited a greater magnitude of Type II adrenal steroid
      receptor activation in brain tissues during stress. In contrast, Type II receptor
      activation in immune tissues of F344 rats following stress was similar to that of
      SD rats. Importantly, LEW rats exhibited the lowest magnitude of activation of
      Type II receptors in immune tissues during stress. No differences were observed
      between strains in the extent of stress-induced Type I adrenal steroid receptor
      activation. The observed differences between strains in corticosteroid-binding
      globulin (CBG) levels in plasma, pituitary, and immune tissue may mediate the
      differential access of corticosterone to neural versus immune tissues. These
      results indicate that strain differences in corticosterone secretion are
      manifested by differences in Type II receptor activation in neural as well as
      immune tissues. Moreover, they suggest that increased access of corticosterone to
      adrenal steroid receptors in brain areas of F344 rats may contribute to
      behavioural differences between strains, whereas decreased access of hormone to
      receptors in immune tissues of LEW rats may contribute to strain differences in
      susceptibility to autoimmune disease.

PMID- 7822485
TI  - Phenotypic analysis of migrant, efferent lymphocytes after implantation of cold
      preserved, peripheral nerve allografts.
AB  - Cold-preservation of peripheral nerve allografts in vitro (3 weeks, 5 degrees C)
      was performed to determine its effect on local lymphocyte migration patterns in
      vivo. Lymphocyte migration was assessed by continuously monitoring the cell
      output in the regional lymph for nearly 1 month. Cold-preservation delayed or
      prevented the typical biphasic increase in efferent lymphocyte output observed
      after fresh allograft implantation. It also decreased the output of activated
      lymphocytes (CD 5 and MHC class II positive) compared with that seen in the fresh
      allograft response. These changes suggest that the host immune response to
      preserved nerve allografts is altered over a prolonged period in vivo (3 weeks).
      Cold-preservation may be a useful method of reducing allograft immunogenicity,
      thereby limiting systemic immunosuppression requirements for the successful
      clinical utilization of peripheral nerve allografts.

PMID- 7822486
TI  - Monoclonal antibody against human glioblastoma multiforme (U-87MG)
      immunoprecipitates a protein of molecular mass 38 kDa and inhibits tumor growth
      in nude mice.
AB  - A monoclonal antibody 6DS1 against a human glioblastoma multiforme cell line U
      87MG recognizes a tumor-specific, cell surface antigen of human glioblastoma cell
      lines. Partial cross-reactivity is observed with two human neuroblastoma cell
      lines, SK-N-SH and SK-N-MC, with little or no reactivity towards a rat glioma
      cell line C6 or normal human adult and fetal brain tissues. The antibody
      recognizes an antigen of molecular mass 38 kDa as inferred from Western blot
      analysis and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the
      immunoprecipitate. The monoclonal antibody 6DS1 inhibits both the attachment to
      substratum and growth of U-87MG cells. It strongly cross-reacts with
      xenotransplants of U-87MG cells and inhibits tumorigenesis (subcutaneous implants
      of U-87MG cells) in nude mice.

PMID- 7822487
TI  - Analysis of CD27 surface expression on T cell subsets in MS patients and control
      individuals.
AB  - Within the peripheral blood, CD4+CD27- T cells only reside within the CD45RA-
      (memory or primed) T cell subset. Cells with this phenotype have characteristics
      of specialized effector T cells according to their cytokine secretion profiles
      and the expression of tissue-specific adhesion molecules. This subset was
      previously found to be increased in certain diseases that are associated with
      immune activation. Therefore we analyzed CD27 expression of peripheral blood and
      CSF T cells in MS patients. Within the CD4+ T cell subset no differences were
      seen between MS patients and controls in proportions of CD45RA-CD27- cells.
      However, when the CD3+ T cell compartment was analyzed, CD27- cells were also
      found within the CD45RA+ subset. These cells, most likely CD8+, are significantly
      reduced in PBL and CSF of MS patients as compared with OND patients. In MS and
      OND groups the level of CD27- cells in peripheral blood correlated significantly
      with that in CSF, indicating a balanced migration of CD27- cells between the two
      compartments. In OIND patients, however, this equilibrium was lost. The
      correlation of the level of CD27+ cells with the amount of intrathecally produced
      IgG in MS patients may suggest that CD27+ cells are responsible for B cell help
      in this disease.

PMID- 7822488
TI  - Ultrastructural and immunocytochemical analysis of the circuitry of two putative
      directionally selective ganglion cells in turtle retina.
AB  - Two well-stained, horseradish peroxidase-filled varieties of putative ON-OFF
      directionally selective ganglion cells, G14a and G15, that project to the
      dorsolateral optic tectum (Guiloff and Kolb [1992a] Vis. Neurosci. 8:295-313)
      were studied qualitatively and quantitatively. Both were bistratified ganglion
      cells with one tier of dendrites in the OFF sublamina and the other in the ON
      sublamina of the inner plexiform layer (IPL). The cells were serially sectioned
      and examined for synaptic inputs by electron microscopy. Portions of the
      dendritic trees were also analyzed after postembedding immunocytochemistry for
      neurotransmitter candidates gamma aminobutyric acid (GABA), glycine, choline
      acetyltransferase (ChAT), and glutamate in presynaptic neurons. Both G14a and G15
      are dominated by amacrine cell inputs and have only minor bipolar cell
      involvement. Probably at least two different types of bipolar cell are
      presynaptic. Both ganglion cells receive some GABA-positive (GABA+) amacrine
      inputs and G14a receives ChAT+ amacrine inputs. Glycine+ and glutamate+ inputs
      could not be detected in either cell. The GABA+ inputs appeared to be regionally
      arranged in the dendritic trees. The general distribution of amacrine and bipolar
      inputs to the two tiers of dendrites in both cell types appeared to be
      asymmetrical, both along the radial extent of the dendritic trees and within the
      depth of the IPL. Our data support some aspects of the current models for
      directional selectivity. We suggest candidate bipolar and amacrine cells that
      could have input to these ganglion cells. Since many of the putative presynaptic
      amacrine cells coincide with directionally selective types recorded and stained
      by other authors, we propose that in turtle retina directional selectivity arises
      in neurons presynaptic to the ganglion cells.

PMID- 7822489
TI  - Localisation of parvalbumin-immunoreactive structures in primate caudate-putamen.
AB  - To investigate the morphology, distribution, and connections of parvalbumin
      containing neurones in the caudate-putamen of primates, perfuse-fixed sections
      were stained to reveal parvalbumin immunoreactivity. In agreement with previous
      observations, the caudate-putamen was rich in parvalbumin-positive neurones and
      neuropil. The neuropil staining was uneven such that the dense background
      staining was interspersed with zones of relatively weak staining. The
      distribution corresponded to the striosome/matrix system as defined by substance
      P or met-enkephalin immunostaining in adjacent sections. Because parvalbumin
      positive neurones are present in regions known to project to the caudate-putamen
      and the majority of parvalbumin-positive terminals in the matrix formed
      asymmetric synapses, it is concluded that the uneven staining is probably due to
      afferents of the neostriatum. The morphology of the parvalbumin-immunoreactive
      neurones varied between the striosomes and matrix; those in the matrix were
      smaller and possessed dendritic arborisations that were relatively uniform,
      whereas those in the striosomes were generally more extensively stained and
      possessed a greater variation in their dendritic branching patterns. The
      dendrites frequently crossed the boundary between the striosomes and matrix. A
      population of giant parvalbumin-immunoreactive neurones was also observed in the
      putamen. Electron microscopic analysis revealed that, in addition to terminals
      forming asymmetric synapses, a smaller population formed symmetric synaptic
      specialisations and are presumed to be derived from the local parvalbumin
      immunoreactive neurones. Terminals of the latter group formed synapses with
      medium-sized spiny neurones. Because parvalbumin-positive neurones receive input
      from the cortex, they may transmit cortical information to spiny neurones.

PMID- 7822490
TI  - Response properties of nociceptive and low-threshold neurons in rat trigeminal
      pars caudalis.
AB  - There is little doubt that trigeminal nociceptive neurons play a critical role in
      signaling the presence of harmful, or potentially harmful, orofacial stimuli.
      Unfortunately, there is only a limited understanding of how these neurons code
      such stimuli and whether this code is maintained in those structures responsible
      for generating overt reactions. The present series of experiments were designed
      to quantitatively document the response properties of nociceptive neurons in the
      rat trigeminal pars caudalis using the same electrical and innocuous and/or
      noxious mechanical and thermal stimuli employed in the characterization of
      nociceptive neurons with orofacial receptive fields in the rat superior
      colliculus. Neurons were classified as either low-threshold mechanoreceptive,
      wide-dynamic-range, or nociceptive-specific (type I, II) depending on their
      responsiveness to these stimuli. Nociceptive pars caudalis neurons (92/135, 68%)
      had receptive field organizations and input fibers (as indicated by latencies to
      electrical stimuli) quite different from those of low-threshold neurons (43/135,
      32%). Nociceptive stimulus-response relationships for the population of wide
      dynamic-range and nociceptive-specific type I neurons to contact heat stimuli
      were positively accelerating power functions with exponents of 3.9 and 4.4,
      respectively. This contrasted sharply with the low-threshold component of wide
      dynamic-range neurons which was a negatively accelerating power function with an
      exponent of 0.7. All categories of nociceptive neurons also responded vigorously
      to cold stimuli. The thresholds of both hot and cold stimuli were often below
      psychophysical estimates of thermal pain, suggesting that "nociceptive" neurons
      process far more information than that required to signal potentially harmful
      stimuli. The fundamental similarities in nociceptive properties in pars caudalis
      and other structures of the central nervous system suggest that there is little
      transformation of the information encoded at successive levels of the neuraxis.
      This is consistent with the idea that the functional role of nociceptive neurons
      is reflected more in which circuits they are integrated and less in differences
      in their physiological properties.

PMID- 7822491
TI  - Peptides related to the Diploptera punctata allatostatins in nonarthropod
      invertebrates: an immunocytochemical survey.
AB  - The allatostatins are a family of peptides isolated originally from the
      cockroach, Diploptera punctata. Related peptides have been identified in
      Periplaneta americana and the blowfly, Calliphora vomitoria. These peptides have
      been shown to be potent inhibitors of juvenile hormone synthesis in these
      species. A peptide inhibitor of juvenile hormone biosynthesis has also been
      isolated from the moth, Manduca sexta; however, this peptide has no structural
      homology with the D. punctata-type allatostatins. Investigations of the phylogeny
      of the D. punctata allatostatin peptide family have been started by examining a
      number of nonarthropod invertebrates for the presence of allatostatin-like
      molecules using immunocytochemistry with antisera directed against the conserved
      C-terminal region of this family. Allatostatin-like immunoreactivity (ALIR) was
      demonstrated in the nervous systems of Hydra oligactis (Hydrozoa), Moniezia
      expansa (Cestoda), Schistosoma mansoni (Trematoda), Artioposthia triangulata
      (Turbellaria), Ascaris suum (Nematoda), Lumbricus terrestris (Oligochaeta), Limax
      pseudoflavus (Gastropoda), and Eledone cirrhosa (Cephalopoda). ALIR could not be
      demonstrated in Ciona intestinalis (Ascidiacea). These results suggest that
      molecules related to the allatostatins may play an important role in nervous
      system function in many invertebrates as well as in insects and that they also
      have an ancient evolutionary lineage.

PMID- 7822492
TI  - Neocortex provides direct synaptic input to interstitial neurons of the
      intermediate zone of kittens and white matter of cats: a light and electron
      microscopic study.
AB  - The existence of direct synaptic input from the neocortex to intermediate zone
      and white matter interstitial neurons was examined in both neonate and adult
      cats. This projection was studied by injecting the anterograde tracer Phaseolus
      vulgaris leucoagglutinin (PHA-L) into the neocortex and examining whether
      cortical efferent axons formed synapses in the intermediate zone or white matter.
      Anterogradely labeled boutons establishing synapses in the intermediate zone and
      white matter were found at the electron microscopic level after injecting PHA-L
      into the primary visual, somatosensory, and suprasylvian cortex. Although labeled
      synapses were found in the intermediate zone of kittens injected at postnatal
      days 2 and 6, their morphological features appeared immature compared to those
      found in kittens aged 3 weeks or in adults. Postsynaptic targets of efferent
      cortical axons were studied in serial sections and shown to be dendritic shafts
      and spines. This paper shows that cortical efferent axons contribute synapses to
      interstitial neurons located in the intermediate zone of kittens and white matter
      of adults. The functional role of the corticointermediate zone/white matter
      projection remains to be determined.

PMID- 7822493
TI  - Localization of salmon gonadotropin-releasing hormone mRNA and peptide in the
      brain of Atlantic salmon and rainbow trout.
AB  - The decapeptide gonadotropin-releasing hormone (GnRH) is a key hormone for the
      central regulation of reproduction. The distribution of salmon GnRH (sGnRH),
      which is the major form in salmonids, has been studied in different fish species
      by immunocytochemistry. Discrepancies in data concerning the distribution of
      sGnRH perikarya led us to investigate this problem in two species, the Atlantic
      salmon and the rainbow trout, with in situ hybridizaiton of sGnRH messenger, a
      highly specific molecular tool. By Northern blot analysis, the rainbow trout
      sGnRH messenger appears to be about 500 bases in length, which is close to those
      isolated from Atlantic salmon or masu salmon and characterized previously. In
      situ hybridization with riboprobes generated with Atlantic salmon sGnRH cDNA
      demonstrated that sGnRH perikarya are restricted to the ventral part of olfactory
      bulbs, telencephalon, and preoptic area. They are distributed on a nearly
      continuous line extending from the olfactory bulbs to the preoptic area in both
      salmonid species studied. Despite the presence of GnRH-like immunoreactivity in
      the preoptic magnocellular nucleus (NPOm) and in the tegmentum of the midbrain
      (MT), the sGnRH mRNA is not present in these two structures. Stained cells in
      NPOm could be target cells for GnRH and immunoreactive neurons in MT are likely
      to be chicken GnRH-II containing cells. Our study not only gives a precise
      distribution of the sGnRH system in two salmonids, Atlantic salmon and rainbow
      trout, but also clarifies the ambiguous data published up to now in rainbow
      trout.

PMID- 7822494
TI  - VGF expression in the brain.
AB  - VGF is a neuronal polypeptide first identified as a cDNA clone in a gene library
      from nerve growth factor-stimulated PC12 cells. In the present paper, the
      expression of VGF is examined for the first time throughout the adult rat central
      nervous system with immunocytochemistry and Northern blot analysis. VGF RNA was
      found in all brain regions studied, including hypothalamus, hippocampus,
      cerebellum, olfactory bulb, and cortex. In contrast to the relatively strong
      immunostaining of hypothalamic neurons, the level of VGF RNA expression in the
      hypothalamus was relatively low in comparison with other brain regions. With the
      aid of antisera raised against bacterially produced recombinant proteins
      containing parts of the VGF sequence, immunoreactive neurons were detected
      throughout the brain, including regions of the olfactory tubercle, caudate
      putamen, thalamus, cortex, amygdala, hypothalamus, midbrain, and hippocampus. VGF
      immunoreactive neurons did not contain detectable amounts of nerve growth factor
      receptor; other neurons that showed nerve growth factor receptor immunoreactivity
      expressed no VGF immunoreactivity. The lack of colocalization of VGF and nerve
      growth factor receptor suggests that, unlike expression in PC12 cells, VGF
      expression in neurons from the central nervous system does not require nerve
      growth factor stimulation. Within the hippocampus, the location of VGF
      immunoreactive cells was suggestive of inhibitory interneurons. VGF
      immunoreactive axons and terminals were found throughout the brain. These
      observations extend our earlier work on VGF expression in the hypothalamus to
      other regions of the brain and support the conclusion that although VGF
      expression is only detected in subsets of neurons in each brain region, these
      subsets are widely distributed throughout the central nervous system.

PMID- 7822495
TI  - Expression of GAP43 mRNA in normally developing and transplanted neurons from the
      rat ventral mesencephalon.
AB  - These experiments were designed to determine whether the neuronal growth-related
      protein GAP43 is expressed at high levels by neurons that collateralize
      extensively or have long periods of synaptogenesis. We also evaluated the effects
      of target availability on GAP43 expression. Dopaminergic neurons of the rat
      ventral mesencephalon (VM) were chosen for investigation because they undergo
      extensive collateralization and synaptogenesis during postnatal development.
      Double label in situ hybridization histochemistry (ISHH) and immunocytochemistry
      (ICC) were used to measure changes in GAP43 mRNA levels within tyrosine
      hydroxylase (TH)-immunoreactive and -nonimmunoreactive neurons of the VM during
      postnatal development (p5-adult). TH neurons show higher levels of GAP43 mRNA
      than do non-TH neurons throughout normal postnatal development and in the adult.
      This result may be due to more extensive axonal arborization and synaptic
      remodeling on the part of TH neurons as they innervate the striatum. To test the
      effects of target availability on GAP43 utilization, grafts of embryonic (e15) VM
      were placed within previously 6-hydroxydopamine (6-OHDA)-lesioned striata and
      allowed to develop for 10-28 days. Levels of GAP43 mRNA in grafted TH neurons
      were reduced at all time points. The short distance to target in the graft
      paradigm may shorten the overall axonal process length, resulting in lower
      requirements for growth-related proteins such as GAP43. However, grafted non-TH
      neurons had elevated levels of GAP43 mRNA, perhaps attributable to prolonged
      target seeking by neurons that have been isolated from their normal targets.

PMID- 7822496
TI  - Verrucous carcinoma of the skin and mucosa.
AB  - The concept of verrucous carcinoma as a clinicopathologic variant of squamous
      cell carcinoma is worthy of recognition. It is known by a confusing array of
      names, such as Ackerman's tumor, Buschke-Loewenstein tumor, florid oral
      papillomatosis, epithelioma cuniculatum, carcinoma cuniculatum, and cutis
      papillomatosis carcinoides of Gottron. Its apparent clinical benignity may lead
      to lengthy periods of misdiagnosis, during which it is likely not to spread to
      distant lymph nodes, but rather to destroy a nose, mandible, or penis as it
      slowly but relentlessly extends into underlying tissue. Morphologically warty or
      verrucous, its relatively bland histologic features are often more suggestive of
      a verruca vulgaris or pseudoepitheliomatous hyperplasia than of squamous cell
      carcinoma to those unfamiliar with the diagnosis. Alternatively, when it extends
      into underlying tissues, it may be mistaken histologically for a benign adnexal
      tumor or even an epidermoid cyst. Therapy may also be challenging because
      recurrences are common and concerns about potential anaplastic transformation
      after radiotherapy are often expressed.

PMID- 7822497
TI  - Guidelines of care for nevi. II. Nonmelanocytic nevi, hamartomas, neoplasms, and
      potentially malignant lesions. Committee on Guidelines of Care.

PMID- 7822498
TI  - Guidelines of care for contact dermatitis. Committee on Guidelines of Care.

PMID- 7822500
TI  - Clinical pearl: use of self-adhesive, compressive wraps in the treatment of limb
      hemangiomas.

PMID- 7822499
TI  - A pharmacogenetic basis for the safe and effective use of azathioprine and other
      thiopurine drugs in dermatologic patients.

PMID- 7822501
TI  - Atrophoderma of Pasini and Pierini: atrophy of dermis or subcutis?

PMID- 7822502
TI  - Hyperkeratosis of the nipple and areola simultaneously developing with cutaneous
      T-cell lymphoma.

PMID- 7822503
TI  - Perforating granuloma annulare: response to treatment with isotretinoin.

PMID- 7822504
TI  - Zosteriform cutaneous T-cell lymphoma.

PMID- 7822505
TI  - Milia-like idiopathic calcinosis cutis and multiple connective tissue nevi in a
      patient with Down syndrome.

PMID- 7822506
TI  - A case of partial face-sparing lipodystrophy combining features of generalized
      lipodystrophy.

PMID- 7822507
TI  - Ranitidine-related toxic epidermal necrolysis in a patient with idiopathic
      thrombocytopenic purpura.

PMID- 7822508
TI  - Multicentric reticulohistiocytosis associated with recurrence of malignant
      melanoma.

PMID- 7822509
TI  - Isotretinoin-associated normalization of hyperbilirubinemia in patients with
      Gilbert's syndrome.

PMID- 7822510
TI  - Generalized bullous pemphigoid controlled by tetracycline therapy alone.

PMID- 7822511
TI  - Efficacy of human intravenous immune globulin in pyoderma gangrenosum.

PMID- 7822513
TI  - Hepatitis and HIV risk review.

PMID- 7822512
TI  - Partial unilateral lentiginosis.

PMID- 7822514
TI  - Estrogen dermatitis.
AB  - BACKGROUND: Autoimmune progesterone dermatitis includes pruritus, urticaria,
      papulovesicular eruptions, and bullous erythema multiforme. Sensitivity to
      estrogen has not been described, although it was probably first recognized almost
      50 years ago. OBJECTIVE: Our purpose was to assess sensitization to selected
      hormones in women with a significant premenstrual flare of skin lesions. METHODS:
      Intradermal skin tests to 18 hormones and control substances were performed in
      seven patients and four control subjects and read for immediate urticarial and
      delayed type reactions. Six other control subjects had only estrone and
      progesterone skin tests. The effect of the antiestrogen tamoxifen on the course
      of the dermatosis was studied. RESULTS: Seven women exhibiting severe
      premenstrual exacerbations of papulovesicular eruptions, urticaria, eczema, or
      generalized pruritus proved to have an unrecognized sensitivity to estrogen. Five
      patients had a positive delayed tuberculin-type skin test to estrogen. Two
      patients with generalized chronic urticaria had only an urticarial reaction to
      intradermal estrogens. Antiestrogen therapy with tamoxifen proved effective in
      all five patients, whereas elimination of oral estrogen therapy cured the other
      two patients. CONCLUSION: Women can become sensitized to their own estrogens; the
      major clue is worsening of the skin problem premenstrually. Positive intradermal
      skin tests to estrogens are diagnostic. Tamoxifen is a specific therapy. We have
      named this disorder estrogen dermatitis.

PMID- 7822515
TI  - Edematous, scarring vasculitic panniculitis: a new multisystemic disease with
      malignant potential.
AB  - BACKGROUND: Hydroa vacciniforme (HV) is a disease of unknown origin characterized
      by erythema, vesicles, necrosis, and varicelliform scars in light-exposed skin.
      Systemic involvement is absent. A few patients have been reported with "severe
      HV" with systemic involvement, development of non-Hodgkin's lymphoma, and a poor
      prognosis. OBJECTIVE: Our purpose was to characterize and differentiate our
      patients' disease from HV. METHODS: We performed a retrospective
      clinicopathologic study of 14 children previously diagnosed as having "severe
      HV." RESULTS: The extension and severity of the cutaneous lesions, fever,
      wasting, failure to thrive, hepatosplenomegaly, vasculitis, panniculitis, and
      potential development of lymphoma are features that clearly differentiate
      edematous scarring vasculitic panniculitis from HV. CONCLUSION: Edematous
      scarring vasculitic panniculitis is a novel multisystemic disease with malignant
      potential that is not related to classic HV.

PMID- 7822516
TI  - Allelic instability in the mitosis model and the inheritance of psoriasis.
AB  - BACKGROUND: Allelic instability in mitosis has been proposed as a model for
      dominantly inherited diseases. OBJECTIVE: Our purpose was to analyze our own and
      published data on the inheritance of psoriasis according to the predictions of
      the allelic instability-in-mitosis model. METHODS: Frequency of psoriasis in
      father, mother, and siblings was extracted or calculated from data in the
      literature. Our case records were reviewed and supplemented by telephone or
      personal interviews when records were incomplete. Inheritance rates from each sex
      of parent were compared. Correlation between ages at onset in affected siblings
      was determined. RESULTS: From our own data and the literature summary, the
      preponderance of inheritance from the father over the mother is statistically
      significant. A direct correlation exists between ages at onset in affected
      siblings. Age at onset in parent and child is also positively correlated. Average
      age at onset in parents is greater than in offspring. CONCLUSION: Both data from
      literature and our own data are in agreement with the predictions of the allelic
      instability in mitosis model. This provides evidence that an unstable gene may
      contribute to the genetics of psoriasis.

PMID- 7822517
TI  - Cumulative effects from repeated exposures to suberythemal doses of UVB and UVA
      in human skin.
AB  - BACKGROUND: The skin is repeatedly exposed to solar UV radiation. Long-term
      photodamage is a consequence of cumulative UV radiation injury. Hence an
      examination of the repetitive effects of UV exposure is more likely to yield
      clues to the early alterations that lead to photoaged skin than a single
      exposure. OBJECTIVE: We examined the effects of repetitive low-dose UV
      irradiation on human skin with the aim of identifying UVA-induced effects that
      may have a different wavelength dependence than acute erythema. METHODS: Areas on
      the lower part of the back were each exposed to a suberythemal dose (0.5 minimal
      erythema dose [MED]) of solar simulated radiation (290 to 400 nm) and of UVA (320
      to 400 nm) once daily, 5 days a week, for 28 doses. One site was also treated
      daily with a sunscreen having a sun protection factor of 22 and then exposed to
      11 MEDs of solar simulated radiation for the same duration. Epidermal and dermal
      changes were analyzed and quantified by histochemical stains in combination with
      computer-assisted image analysis of tissue sections. RESULTS: At equal 0.5 MED
      doses, UVA induced greater cumulative changes than solar simulated radiation, as
      assessed by development of a greater cumulative erythema response in the first
      week of treatment, the presence of epidermal hyperplasia and stratum corneum
      thickening, depletion of Langerhans cells, dermal inflammatory infiltrates, and
      deposition of lysozyme on elastin fibers. These changes were not prevented by the
      sunscreen. A single short-term dose of UVA did not elicit these changes.
      CONCLUSION: These findings suggest that UVA may contribute significantly to long
      term actinic damage and that the spectral dependence for cumulative damage does
      not parallel the action spectrum for acute injury (erythema) in human beings.

PMID- 7822518
TI  - Persistent actinic epidermolytic hyperkeratosis.
AB  - BACKGROUND: Epidermolytic hyperkeratosis is a distinctive histologic change noted
      in a variety of acquired and congenital dermatoses. Its pathogenesis is unknown.
      We have observed acquired epidermolytic hyperkeratosis in four Japanese men.
      OBJECTIVE: Our purpose was to report four cases of acquired epidermolytic
      hyperkeratosis induced by sun exposure. METHODS: Four cases were studied
      clinically, histopathologically, electron microscopically, and by tissue culture.
      RESULTS: Flat, keratotic, slightly elevated, depigmented papules were located on
      the upper back, shoulders, and anterior aspect of the thighs. They appeared after
      excessive sun exposure. Depigmented macules coexisted with the pigmented macules.
      Histologic and ultrastructural examination revealed epidermolytic hyperkeratosis.
      Thick bundles of tonofilaments, which were also present in the cutaneous lesions,
      were seen in newly proliferated keratinocytes in cultures taken from depigmented
      papules. CONCLUSION: These results suggest that acquired epidermolytic
      hyperkeratosis may be induced by excessive sun exposure. We propose the term
      persistent actinic epidermolytic hyperkeratosis for these lesions.

PMID- 7822519
TI  - Calcipotriene ointment 0.005% for psoriasis: a safety and efficacy study.
      Calcipotriene Study Group.
AB  - BACKGROUND: Plaque psoriasis of mild to moderate severity is routinely treated
      with topical steroids and coal tar along with emollients. A safe and convenient
      new treatment modality would be of value to most patients with psoriasis.
      OBJECTIVE: Our purpose was to evaluate the safety and efficacy of a new vitamin
      D3 analogue, calcipotriene, for the treatment of plaque psoriasis. METHODS: Twice
      daily dosing of calcipotriene was compared with its vehicle, for up to 8 weeks,
      in a double-blind study of 277 patients at 10 study centers in the United States.
      Two hundred forty-seven patients completed the trial. The clinical
      characteristics of plaque elevation, erythema, scaling, and overall disease
      severity were evaluated at baseline and after 1, 2, 4, 6, and 8 weeks of
      treatment. A Physician's Global Assessment of improvement or worsening of the
      disease was performed after 1, 2, 4, 6, and 8 weeks of treatment. Blood and urine
      samples, for routine clinical laboratory tests, were collected at baseline and
      after 1, 2, 4, and 8 weeks of treatment. RESULTS: As early as the week 1
      evaluation, patients treated with calcipotriene ointment 0.005% had significantly
      lower mean scores (p = 0.043) than the vehicle-treated patients for the disease
      characteristics of plaque elevation, erythema, and scaling. This trend continued
      through week 8 of treatment when 70% of the calcipotriene-treated patients showed
      75% or more improvement compared with only 19% of vehicle-treated patients. Only
      minor treatment-related adverse events were observed. There were no abnormal
      laboratory results judged related to treatment and the rare instances of elevated
      serum calcium values were equally distributed between active and vehicle
      treatments. CONCLUSION: This study provides evidence that calcipotriene is a
      safe, effective, and promising new agent for the treatment of moderately severe
      plaque psoriasis.

PMID- 7822520
TI  - Short-duration treatment of fingernail dermatophytosis: a randomized, double
      blind study with terbinafine and griseofulvin. LAGOS III Study Group.
AB  - BACKGROUND: Dermatophytic infections of the fingernail can be effectively treated
      with oral antifungal agents; however, a long duration of treatment, generally
      several months, is required for cure. OBJECTIVE: Our purpose was to compare the
      efficacies of short-duration treatment with terbinafine and griseofulvin in the
      management of fingernail dermatophytosis. METHODS: In this randomized, double
      blind study 180 patients with fingernail dermatophytosis were treated with daily
      doses of either terbinafine, 250 mg/day, or microsized griseofulvin, 500 mg/day,
      for 12 weeks. Patients subsequently received placebo for 12 weeks and were
      observed for an additional 24 weeks. Drug efficacy was assessed by mycologic
      examination and measurement of the growth of unaffected nail. RESULTS: At the end
      of the study 76% of the group who received terbinafine and 39% of those who
      received griseofulvin were found to be completely cured (p = 0.001). Drug
      tolerability was equally good in both treatment groups, without any clinically
      relevant changes in laboratory biochemical values. CONCLUSION: Short-duration
      treatment (3 months) for fingernail dermatophytosis with terbinafine and
      griseofulvin is well tolerated. However, terbinafine was associated with a higher
      cure rate.

PMID- 7822522
TI  - Guidelines of care for warts: human papillomavirus. Committee on Guidelines of
      Care.

PMID- 7822521
TI  - Low-dose short-term cyclosporine versus etretinate in psoriasis: improvement of
      skin, nail, and joint involvement.
AB  - BACKGROUND: High-dose cyclosporine therapy significantly alleviates psoriasis
      within 2 to 4 weeks but is associated with a high rate of side effects. Reports
      are conflicting on the frequency and promptness of relapse after discontinuation
      of cyclosporine therapy. OBJECTIVE: Our purpose was to compare the efficacy and
      safety of low-dose cyclosporine with that of etretinate and the stability of
      remission after replacing cyclosporine therapy with topical anthralin during
      tapering of cyclosporine. METHODS: In a multicenter study 210 patients with
      moderate to severe chronic plaque-type psoriasis were randomly assigned to
      treatment with cyclosporine or etretinate. The initial dosages were 2.5 mg/kg/day
      for cyclosporine and 0.5 mg/kg/day for etretinate, which could be individually
      adjusted to 5.0 and 0.75 mg/kg/day, respectively. After a treatment phase of 10
      weeks (phase 1) patients receiving cyclosporine were again randomly assigned to a
      group in which cyclosporine was replaced by topical dithranol (anthralin), or to
      another group in which the drug was tapered during the next 12 weeks (phase 2).
      All patients treated with etretinate discontinued therapy after 10 weeks and used
      topical dithranol. RESULTS: Mean Psoriasis Area and Severity Index decreased by
      71% in the cyclosporine group and by 47% in the etretinate group during phase 1.
      After 10 weeks of treatment 47% of the patients treated with cyclosporine and 10%
      of those treated with etretinate showed a reduction of more than 80% in skin
      involvement. Sixty-four percent of the cyclosporine group and 48% of the
      etretinate group did not require an increase in the initial dosage, resulting in
      a mean daily dose of 3.0 and 0.53 mg/kg, respectively. There was significant
      alleviation of nail involvement and joint complaints in both groups. In phase 2
      the increase in mean Psoriasis Area and Severity Index and the incidence of
      relapse were significantly higher in patients in whom cyclosporine was
      discontinued and replaced by dithranol than in patients in whom cyclosporine was
      tapered or who were pretreated with etretinate. During treatment four patients
      from the cyclosporine group and three patients of the etretinate group
      discontinued the study because of side effects. CONCLUSION: Low-dose short-term
      cyclosporine therapy for psoriasis is, in comparison with etretinate, highly
      effective and well tolerated. Individually adjusted cyclosporine therapy allows
      the majority of patients to continue the low dosage of 2.5 mg/kg/day and still
      achieve a good clinical response. Remission can be better preserved by tapering
      the drug than by discontinuing treatment abruptly.

PMID- 7822523
TI  - High resolution GRASE MRI of the brain and spine: 512 and 1024 matrix imaging.
AB  - OBJECTIVE: Our goal was to implement 512 and 1024 matrix MRI of the brain in
      clinically acceptable imaging times. MATERIALS AND METHODS: With use of the GRASE
      (gradient-SE) imaging technique, 3 signals are refocused from each of 16 SEs,
      giving a total of 48 echoes per echo train, for a speed advantage of 1/48 over
      conventional SE imaging. Images in 1024 matrices are acquired in 2D Fourier
      transform (FT) multisectional MRI. In related experiments, multislab 3D FT GRASE
      imaging is performed using 16 partitions/slab, providing thinner 1 to 2 mm
      sections. In all imaging experiments, higher spatial resolution is obtained with
      stronger and faster gradients, 24 mT/m in 625 microseconds rise time, on a
      standard commercial MRI system. RESULTS: The 2D FT 1024 matrix images of the head
      were acquired in 4:20 min, with 20 sections and TR/TE 7040/115 ms in a
      rectangular FOV to obtain .28 x .27 mm2 spatial resolution. Small anatomic
      structures, including cochlea of inner ear, cranial nerves, and vascular detail,
      are readily demonstrated. The 512 matrix images were obtained in 4:40 min, with
      16 sections and TR/TE 3,500/104 ms in a 24 cm FOV. The 3D FT technique
      substantially increased slice coverage as well as image signal-to-noise ratio.
      CONCLUSION: The results show that 1024 matrix MRI is technically feasible in
      clinically acceptable imaging time and offers advantage for high resolution
      imaging. Optimization of 1024 matrix and 3D FT GRASE imaging should improve the
      delineation of anatomic regions of interest.

PMID- 7822524
TI  - MR appearance of periosteal chondrosarcoma of the foot.
AB  - OBJECTIVE: To assess the role of MRI in evaluating periosteal chondrosarcoma in
      the foot, an anatomically complicated location. MATERIALS AND METHODS: Three
      cases of surgically and histologically confirmed periosteal chondrosarcomas
      occurring in the foot (58-year-old woman, 57-year-old woman, and 63-year-old man)
      were retrospectively reviewed with an emphasis on MR findings. RESULTS: Magnetic
      resonance successfully delineated the hypovascular nature and lobulating pattern
      of the lesion suggesting the cartilaginous component, the periosteal location
      with sparing bone marrow, and the extent of involvement of adjacent structures.
      These findings were either not seen or less clearly seen on CT in the former two
      cases. CONCLUSION: In cases of periosteal chondrosarcomas in the foot MRI can
      play a significant role both in the characterization of the lesion and in
      planning surgical therapy.

PMID- 7822525
TI  - Significance of QCT bone mineral density and its standard deviation as parameters
      to evaluate osteoporosis.
AB  - OBJECTIVE: A study using quantitative CT (QCT) of the spine was carried out to
      determine whether the standard deviation (SD) of the bone mineral density (BMD)
      within a given region of interest (ROI) could be used as a parameter to evaluate
      osteoporosis. MATERIALS AND METHODS: A low dose single energy protocol was used.
      The elliptical ROIs inside the trabecular bone of the vertebral bodies T12-L3
      were analyzed for four patient groups: Group 1, 52 healthy premenopausal women
      (age 41 +/- 2 years); group 2, 119 healthy early postmenopausal women (53 +/- 4
      years); group 3, 45 postmenopausal relatively healthy women (age 65 +/- 5 years);
      group 4, 26 osteoporotic women (age 67 +/- 5 years). Average group mean BMD
      values and their coefficients of variation (CV = SD/BMD) were calculated. The t
      values, percent decrements, z-scores, and analysis of variance (ANOVA) served to
      compare capabilities of the BMD and the CV to discriminate groups pairwise using
      all possible group combinations. RESULTS: The use of z-scores and percent
      decrements gave ambivalent and mostly insignificant results. The CV performed
      better than BMD in separating group pairs (1,3), (1,4), (2,3), and (2,4), but BMD
      was superior for group pairs (1,2) and (3,4). Using SD as an independent variable
      in addition to age and BMD in the ANOVA did not significantly change r2 or the
      standard error of the estimate. The t test showed highly significant better
      discriminatory capabilities for BMD compared to CV> CONCLUSION: The results of
      our study did not indicate a significant potential of the BMD SD as measured in
      trabecular single energy low dose spinal QCT to improve the discriminatory
      capabilities of BMD for a separation of osteoporotic from nonosteoporotic
      subjects.

PMID- 7822526
TI  - Accuracy of surface fit registration for PET and MR brain images using full and
      incomplete brain surfaces.
AB  - OBJECTIVE: The accuracy of a surface-fitting image registration technique has
      been investigated for matching [18F]fluorodeoxyglucose (FDG) and [15O]H2O PET
      brain images with MR images. Use of partial-brain surfaces (a single hemisphere
      or a limited number of slices) was investigated to simulate cases in which severe
      brain defects or limited axial field of view would preclude using the entire
      brain surface. MATERIALS AND METHODS: Three FDG and three H2O scans were
      performed on five volunteers, in addition to volume MR studies. Fiducial markers
      were placed on the subjects' scalps to provide references for registration
      accuracy. The registration procedure was applied to each PET-MR set, using the
      surfaces defined by locating the brain edge in multiple slices for each set.
      RESULTS: The surfaces fit well, with only 1% scaling necessary for the best fit.
      Errors in fiducial marker positions between MRI and transformed PET were < 2 mm
      in the transverse directions and < 4.5 mm in the axial direction. Fits based on
      the partial surfaces worked well and gave results very similar to the full-brain
      fits. CONCLUSION: The surface-fitting technique is accurate for FDG and H2O PET
      studies, even when part of the brain surface cannot be used.

PMID- 7822527
TI  - MR evaluation of intrapulmonary hematoma.
AB  - We report a case of circumscribed intrapulmonary hematoma, in which MR findings
      were useful in establishing the diagnosis. It is usually easy to make a diagnosis
      of intrapulmonary hematoma using conventional methods, when clinical history of
      trauma and regression of the mass can be observed on serial radiography. However,
      in this case the mass remained almost unchanged 4 months after trauma on chest
      radiography and CT. Magnetic resonance revealed a hyperintense mass with an even
      higher signal rim on T1-weighted imaging and an irregular hyperintense mass on
      T2*-weighted imaging. We made a diagnosis of pulmonary hematoma based on these MR
      findings. Follow-up chest radiography and CT taken 1 year after the injury,
      revealed a substantial decrease in the size of the mass, which confirmed the
      diagnosis. As in this case, some intrapulmonary hematomas regress very slowly or
      may even increase in size, and diagnosis can be difficult with conventional
      methods. In such cases, MRI can be helpful.

PMID- 7822528
TI  - Detection of Palmaz-Schatz stent by ultrafast CT.
AB  - We present a case of Palmaz-Schatz stent in the anterior descending coronary
      artery in a patient in whom restenosis occurred repeatedly after balloon
      angioplasty. The location of the stent was confirmed by ultrafast CT. The Palmaz
      Schatz stent is barely visible by fluoroscopy and confirmation of its location by
      fluoroscopy is difficult after failure of stent delivery. However, ultrafast CT
      enabled the clear detection of a Palmaz-Schatz stent without artifacts and may be
      valuable in confirming its location.

PMID- 7822529
TI  - Epidermoid cyst of the liver complicated by microscopic squamous cell carcinoma:
      CT, ultrasound, and pathology.
AB  - Though cystic hepatic lesions may have features that help characterize them by
      noninvasive imaging modalities, these findings are often nonspecific and may be
      unable to establish the presence of malignancy. This is illustrated here by
      describing an epidermoid cyst of the liver containing microscopic foci of
      squamous cell carcinoma. The importance of totally resecting an epidermoid cyst
      of the liver is emphasized.

PMID- 7822530
TI  - CT demonstration of portal vein remnant within metastatic liver tumor.
AB  - We describe a patient with a metastatic liver tumor that showed a cordlike shadow
      traversing the tumor on CT. Histopathologically, this cordlike shadow within the
      metastatic liver tumor was proved to be an infiltrated portal vein without blood
      flow surrounded by fibrous tissue. Vascular structures traversing a focal lesion
      may be seen not only in focal fatty infiltration or lymphoma but also in
      metastatic liver tumor.

PMID- 7822531
TI  - Dropped gallstones after laparoscopic cholecystectomy mimicking appendicitis: CT
      features.
AB  - We present a case in which clinical and ultrasonographic features of dropped
      gallstones after laparoscopic cholecystectomy mimicked appendicitis.

PMID- 7822532
TI  - Juxtaglomerular cell tumor: MR findings.
AB  - Juxtaglomerular (JG) cell tumor is a rare benign neoplasm of the kidney that
      typically presents with hypertension, secondary hyperaldosteronism, hypocalcemia,
      and hyperreninism. We describe a case of JG cell tumor diagnosed with MRI.

PMID- 7822533
TI  - Segmental autotransplantation of the distal pancreas to the thigh: CT and
      ultrasound features.
AB  - In select patients with pancreatitis, pancreatectomy may be the only alternative
      for treatment of abdominal pain. Segmental autotransplantation of the distal
      pancreas to the thigh has been shown to be successful in preventing or reducing
      the severity of diabetes following pancreatectomy. We present the postoperative
      anatomy and potential complications identified on cross-sectional imaging.

PMID- 7822534
TI  - CT and MR patterns of spinal involvement in Richter syndrome.
AB  - Richter syndrome is the transformation of chronic lymphocytic leukemia (CLL) into
      large cell lymphoma. Besides the involvement of lymph nodes, liver, and spleen,
      bone lesions occur infrequently. We report one case of a patient with a
      paraspinous mass and destruction of the vertebra by large cell transformation of
      CLL seen on CT and MRI. There was nothing specific about the clinical
      presentation, imaging characteristics, and histopathological pattern of bone
      biopsy that would allow for confident differentiation from infectious
      spondylitis.

PMID- 7822535
TI  - CNS Nocardia in AIDS patients: CT and MRI with pathologic correlation.
AB  - OBJECTIVE: Since CNS nocardiosis is an often fatal yet potentially treatable
      infection in HIV patients, we sought to identify and characterize imaging
      features that may suggest the diagnosis in the appropriate clinical setting.
      MATERIALS AND METHODS: The CT scan (six), MR scans (one), or both (two) were
      evaluated in nine HIV patients with pathologically proven CNS Nocardia
      asteroides. Chest X-ray films were available in seven patients. Findings were
      correlated with pathologic examination. RESULTS: All nine patients had brain
      abscesses, and in seven that received intravenous contrast agent, all lesions
      demonstrated ring enhancement. Five of nine patients had hydrocephalus and four
      of these had clinical evidence of meningitis. Small subependymal nodules were
      seen in five of nine patients and four of these also had meningitis. Pathologic
      examination in three of nine cases demonstrated a dense inflammatory infiltrate
      lining the ventricles that extended through the ependymal lining, producing small
      subependymal abscesses. Six of seven available chest X-ray films demonstrated
      infiltrates due to Nocardia. CONCLUSION: Our radiologic-pathologic correlation
      indicates that in an HIV-positive patient with enhancing parenchymal lesions, the
      additional findings of subependymal nodules and/or meningitis may suggest the
      diagnosis of nocardiosis. An associated pulmonary infiltrate can provide a clue
      to the diagnosis and serve as more accessible site for biopsy or culture.

PMID- 7822536
TI  - Internal carotid artery dissection associated with pituitary apoplexy: MR
      findings.
AB  - Pituitary apoplexy almost invariably occurs following hemorrhage into a pituitary
      neoplasm. We report a case in which pituitary apoplexy occurred in the setting
      of, and probably secondary to, dissection of the internal carotid artery.

PMID- 7822537
TI  - Post-traumatic epidermoid cyst: CT appearance.
AB  - We report development of an intracranial epidermoid cyst 2 years after a
      depressed skull fracture. The epidermoid cyst is presumed to be the result of
      introduction of epidermal elements at the time of trauma. Post-traumatic
      intracranial epidermoid cysts are rare and appear to be less common than those
      occurring in the spine.

PMID- 7822538
TI  - CT findings in pulmonary endometriosis.

PMID- 7822539
TI  - Fibrovascular polyps of the esophagus: MRI findings.

PMID- 7822540
TI  - The temporalis tendon: CT and MR appearance.

PMID- 7822541
TI  - MRI of an accessory semimembranosus muscle.

PMID- 7822542
TI  - Cine MRI of the TMJ: need for initial closed mouth images without the Burnett
      device.
AB  - OBJECTIVE: To evaluate the Burnett device when studying functional and
      morphologic aspects of internal derangements of the temporomandibular joint (TMJ)
      with cine MRI. MATERIALS AND METHODS: A patient with clicks in the TMJ cycle was
      studied with dynamic cine MRI both prior to the placement of the Burnett device
      and with the Burnett device in position. RESULTS: Review of MRI revealed clear
      anterior displacement of the disk in relation to the condylar head in true closed
      mouth position without the Burnett device in place. CONCLUSION: Closed mouth off
      sagittal imaging of the disk in the closed mouth position should be included
      prior to appliance placement to detect anterior displacements with very early
      recapture.

PMID- 7822543
TI  - MR evaluation of acoustic schwannoma with fractional contrast doses.
AB  - OBJECTIVE: To investigate the utility of lower contrast medium doses for the
      detection and conspicuity of acoustic schwannomas. MATERIALS AND METHODS: The L/B
      (L, lesion; B, background) ratios or lesion contrast of 17 pathologically proven
      acoustic schwannomas studied with a standard dose (0.1 mmol/kg) of gadopentetate
      dimeglumine was measured. In addition, 22 patients with acoustic schwannomas were
      studied prospectively with fractional doses using the incremental dose technique.
      Each patient received an initial bolus injection of one-eight the standard dose
      (0.0125 mmol/kg) followed by an injection of one-eighth, one-fourth, and one-half
      the standard dose at 5 min intervals to achieve a cumulative dose of one-fourth,
      one-half and full dose, respectively. Imaging was performed immediately after
      each injection. RESULTS: Standard dose--The L/B ratios of pathologically proven
      acoustic schwannomas to mastoid air cells ranged from 14.8 to 41.2 (mean +/- SEM,
      28.0 +/- 1.95), which were approximately 17 times more than those of
      intraparenchymal lesions. Fractional cumulative dose--Qualitative visual analysis
      demonstrated that all acoustic schwannomas showed apparent enhancement at one
      fourth dose. Intense enhancement was noted at one-half and full dose.
      Quantitative analysis demonstrated the mean L/B ratios between the acoustic
      schwannomas and mastoid air cells of the precontrast and one-eighth, one-fourth,
      one-half, and full dose studies were 8.33 +/- 0.52, 11.21 +/- 0.75, 13.02 +/-
      0.83, 15.38 +/- 0.98, and 18.03 +/- 1.36, respectively. CONCLUSION: The L/B
      ratios or lesion contrast of acoustic schwannomas at various fractional contrast
      medium doses was significantly higher compared with that of intraparenchymal
      lesions. Thus, the standard contrast medium dose may not be necessary for
      detection of acoustic schwannomas, and a fractional dose may be sufficient.
      Although the optimal fractional dose remains to be determined, one-half of the
      standard dose (0.05 mmol/kg) appears to be sufficient because of intense
      enhancement at this dose.

PMID- 7822544
TI  - Does postcontrast MR enhancement in lumbar disk herniation have prognostic value?
AB  - OBJECTIVE: The aim of our study was to evaluate the prognostic value, if any, of
      Gd-enhanced MR in patients with lumbar disk herniation. MATERIALS AND METHODS:
      Fifteen patients undergoing conservative treatment for acute lumbar disk
      herniation were included in a prospective Gd-DTPA follow-up MR study. In each
      patient, the size of the herniation was measured, and, according to the changes
      in pathology that occurred, patients were divided into four categories. In
      addition, on the basis of the clinical outcome patients were divided into three
      classes. RESULTS: In 11 of 15 patients, MR performed in the acute phase of the
      disease showed Gd-DTPA enhancement around the herniated disk; in all cases, disk
      herniation was markedly reduced at follow-up MRIs. The clinical outcome was good.
      In the remaining four cases, no enhancement was evident in the acute phase or at
      follow-up MRIs; no modification in the size of disk herniation was demonstrated
      at follow-up in two. Symptoms were unchanged in two patients and mildly improved
      in one. CONCLUSION: Epidural enhancement, which is likely related to an
      inflammatory process, seems to play a role in the modification of the size of
      disk herniation.

PMID- 7822545
TI  - Video loop MRI of ocular motility disorders.
AB  - OBJECTIVE: Our aim was to evaluate a novel means of assessing ocular motility
      disorders using MRI. MATERIALS AND METHODS: A GE image of the orbit was acquired
      in a set plane each time the patient fixed on a series of points spread across
      the field of view. The images were transferred in sequence to a video recorder to
      create a cineloop of ocular movement. The technique was used in 33 patients with
      a range of ocular motility disorders including thyroid eye disease, posttraumatic
      diplopia, and Duane syndrome. RESULTS: In addition to anatomical detail,
      functional information could be derived from motion of the globe, motion of the
      optic nerve, and contractility of individual muscles. This is of particular use
      to the ophthalmic surgeon in disorders of ocular motility following eye surgery.
      CONCLUSION: A method of recording eye movements using MRI is described that
      offers useful functional information in the evaluation of disorders of ocular
      motility.

PMID- 7822546
TI  - Dual kV CT to detect calcification in solitary pulmonary nodule.
AB  - OBJECTIVE: At the high kVp values used in CT scanning, almost all interactions in
      soft tissues occur by Compton scattering. By lowering the kVp close to the k-edge
      of calcium, beam attenuation by calcium will be greater and will be reflected as
      an increase in density reading (DR). The presence of calcification in solitary
      pulmonary nodules (SPNs), and thus an implied benign etiology, is currently being
      diagnosed on CT by using reference phantoms. We explored the possibility of
      utilizing low kVp (i.e., 80 kVp) to detect the presence of such calcification in
      SPNs, thus obviating the need for expensive and cumbersome reference phantoms.
      MATERIALS AND METHODS: We first tested this phenomenon of photoelectric
      interaction by CT and its effect on DRs by scanning various dilutions of calcium
      bicarbonate solution at the standard 140 kVp and at a lower, 80 kVp, setting.
      After confirming the hypothesis, we conducted a prospective clinical study of 27
      consecutive SPNs and scanned them at 140 and 80 kVp to detect the presence of
      calcification by measuring their DRs at both kVp values. RESULTS: All calcium
      solutions showed an increase in DR on the 80 kVp scan. Of the 27 nodules, 11
      (41%) showed an increase in DR, suggesting the presence of calcification: 10
      (91%) were benign, and 1 (9%) was malignant. CONCLUSION: Our study demonstrates
      that dual kVp CT could be reliably used to identify calcifications in SPNs, very
      similar to the use of the reference phantoms currently being applied for the
      purpose.

PMID- 7822547
TI  - Lipoid pneumonia: CT findings.
AB  - OBJECTIVE: To assess the CT findings of lipoid pneumonia. METHODS: Chest
      radiography and CT performed in six patients with proven lipoid pneumonia were
      reviewed by two observers. Diagnosis was confirmed by biopsy (five cases) or
      bronchoalveolar lavage (one case). The clinical history of taking oily substance
      could be obtained retrospectively in all patients. RESULTS: Chest radiography
      showed bilateral air space consolidation in three cases, irregular mass-like
      lesions in two, and a reticulonodular pattern in one case. Computed tomography
      demonstrated diffuse parenchymal consolidation in three cases, localized areas of
      consolidation in two, and subpleural pulmonary fibrosis in one case. In two
      cases, fat with localized areas of consolidation could be seen on CT. In three
      cases with diffuse consolidation the attenuation was decreased but higher than
      that of subcutaneous fat. In one case with subpleural fibrosis no areas of low
      attenuation could be seen on CT. CONCLUSION: We conclude that in patients with
      lipoid pneumonia CT may demonstrate areas with low attenuation diagnostic of fat
      or areas with nonspecific low attenuation or soft tissue density.

PMID- 7822548
TI  - Pulmonary nocardiosis: CT findings.
AB  - OBJECTIVE: To evaluate CT findings of pulmonary nocardiosis in immunocompromised
      patients. MATERIALS ALND METHODS: Five patients with bacteriologically confirmed
      pulmonary nocardiosis were evaluated. Four patients were receiving
      corticosteroids with or without other immunosuppressive drugs for lupus nephritis
      (two patients), idiopathic thrombocytopenic purpura (one patient), and renal
      transplantation (one patient), and one patient had long-standing diabetes.
      Nocardia asteroides was isolated from blood culture, bronchial washing,
      pleuropulmonary aspirates, or open lung biopsy. Plain chest radiography and CT
      were performed on all patients, and follow-up CT was performed on one patient.
      RESULTS: On CT there were pleural effusion (four patients), air-space
      consolidation with internal low attenuation with or without cavities (four
      patients), multiple noncavitating pulmonary nodules and subpleural pulmonary
      nodules (three patients), and chest wall extension (three patients). Follow-up CT
      after treatment showed marked improvement of the pleural and pulmonary lesions.
      CONCLUSION: In the immunocompromised and chronically debilitated host, pulmonary
      nocardiosis should be included in differential diagnosis if chest CT shows
      consolidation with low attenuation areas with or without cavitation, multiple
      pulmonary nodules, pleural effusion, and chest wall extension.

PMID- 7822549
TI  - MRI of coronary arteries: 2D breath-hold vs 3D respiratory-gated acquisition.
AB  - OBJECTIVE: Respiratory motion degrades MR images of the coronary arteries. The
      purpose of this study was to assess and compare two methods of reducing the
      effects of respiration in coronary artery MRI. Single-slice 2D imaging with
      breath-holding and a respiratory-gated 3D technique were used. MATERIALS AND
      METHODS: A comparison was made in 10 normal subjects between a 2D multiple breath
      holding approach and a 3D technique with and without retrospective respiratory
      gating in imaging the coronary arteries. RESULTS: Respiratory gating improved the
      image quality in 76% of the 3D images. Both the 2D and the 3D approaches were
      capable of visualizing the proximal parts of the coronary arteries, with
      comparable vessel length and diameter. The image quality was somewhat better for
      images obtained by breath-holding in 83% of the vessels, probably due to less
      blurring by remnant respiratory motion and higher inflow contrast. CONCLUSION:
      The 2D breath-holding approach reveals a better image quality. However, the 3D
      respiratory-gated acquisition is less operator dependent, faster, and less
      strenuous for patients.

PMID- 7822550
TI  - MR-guided localization of suspected breast lesions detected exclusively by
      postcontrast MRI.
AB  - OBJECTIVE: We describe and evaluate a preoperative MRI localization procedure for
      suspected breast lesions. MATERIALS AND METHODS: Fourteen consecutive patients
      underwent MR localization of suspected breast lesions discovered with contrast
      enhanced MRI but not detected by conventional mammography or ultrasound. In each
      case diagnostic MRI was repeated after the application of special skin markers. A
      non-magnetic wire was subsequently inserted into the breast and a second MRI
      performed to document the position of the wire tip relative to the lesion.
      RESULTS: The procedure was successful in all 14 patients, enabling excision of
      the lesion and allowing histological diagnoses. CONCLUSION: We found the
      described procedure to be quite useful.

PMID- 7822551
TI  - Dynamic MRI of the diaphragm.
AB  - OBJECTIVE: To demonstrate the appearance of the diaphragm on single-slice dynamic
      MRI. MATERIALS AND METHODS: We evaluated the diaphragm using gadolinium-enhanced
      single-slice dynamic MR in 53 patients. RESULTS: The diaphragm was partially
      depicted in 49 cases (92.5%). Its thickest part measured 4.4 +/- 2.2 mm, range 3
      to 15 mm. Enhanced high-intensity thin layer structures were partially identified
      between the diaphragm and liver parenchyma in 46 cases (86.8%) at 16 to 144 s
      (mean +/- SD, 65.7 +/- 32.6 s) after intravenous injection of Gd-DTPA.
      CONCLUSION: Dynamic MR has value and limitations in demonstrating the diaphragm.

PMID- 7822552
TI  - The optimal temporal window for CT of the liver using a time-density analysis:
      implications for helical (spiral) CT.
AB  - OBJECTIVE: Scanning protocols for conventional CT of the liver have been
      proposed. Current availability of helical CT with a four- to sixfold decrease in
      scan time requires significant adjustments in these protocols. The present study
      assesses the implications of time-density curves on the performance of helical
      liver CT. MATERIALS AND METHODS: Twenty patients without liver lesions were
      studied for time-density analysis of the aorta, inferior vena cava (ICV), portal
      vein, and liver. Scans were performed at the level of the portal vein at baseline
      and every 15 s for 3 min following uniphasic administration of 150 ml (300 mg
      I/ml) nonionic contrast agent. Regions of interest were used to measure three
      areas in each anatomic structure over time. Median and mean peak enhancement
      times were calculated for all 20 patients. Cubic spline interpretation was
      employed to determine the point of equilibrium. RESULTS: Results demonstrated the
      following average maximum enhancement values and times for peak enhancement:
      aorta: 227 HU (75 s); liver: 123 HU (105 s); portal vein: 187 HU (90 s); IVC: 142
      HU (90 s). Hepatic enhancement achieved 67 HU over baseline. Peak portal
      enhancement occurred 15 s prior to liver enhancement (p = 0.001). Aortic and
      hepatic curves became parallel (onset of equilibrium) at a median time of 120 s.
      CONCLUSION: Helical scanning requires a longer delay (70-80 s) than used for
      conventional CT. Upon application of these principles, scan initiation occurs
      higher on the liver enhancement curve, improving liver enhancement without
      impinging on equilibrium.

PMID- 7822553
TI  - Phased array RF coils for high-resolution MRI of the inner ear and brain stem.
AB  - OBJECTIVE: The spatial resolution in MRI is predominantly limited by the
      available signal-to-noise ratio (S/N). To increase the S/N, a four coil phased
      array consisting of bilateral pairs of semioval coils was constructed for high
      resolution imaging of the temporal bone and brainstem. MATERIALS AND METHODS:
      Coil sizes of 10 x 6 and 6 x 4.5 cm were tested. The S/N values were measured in
      vivo and with homogeneous phantoms and compared to commercial 3 in receive and
      quadrature head coils. RESULTS: At a depth of 4-5 cm, phantom studies yielded S/N
      improvements of a factor of 1.26-1.37 with the large array compared to the 3 in
      coil and 2.33-1.74 compared to the head coil. Similar improvements (1.16 and
      2.37) were obtained in inner ear images. No further improvement was achieved at
      this depth with the small array. At a depth of 8 cm, phantom studies yielded
      similar S/N for the quadrature head coil and two bilaterally placed large array
      coils, while a factor of 1.27 was obtained in brainstem images. CONCLUSION: The
      use of phased array coils yields significantly increased S/N and is thus valuable
      for high resolution MRI.

PMID- 7822554
TI  - Inflammatory pseudotumor of the liver: radiologic-pathologic correlation.
AB  - OBJECTIVE: To report the imaging appearance of inflammatory pseudotumor of the
      liver with pathologic correlation in three cases. MATERIALS AND METHODS:
      Sonography and CT were performed in all cases. Two lesions were evaluated with
      MRI. All lesions were resected, and imaging data and histopathology were
      correlated. RESULTS: In all three cases ultrasonography revealed a hypoechoic
      well-circumscribed mass. In one case CT showed a hypodense homogeneous lesion
      with central calcifications. No enhancement was demonstrated on postcontrast CT.
      The lesion appeared hypointense relative to the adjacent liver on T1-weighted MRI
      and isointense on T2-weighted MRI. A perilesional rim was detected in all cases
      on postcontract CT and/or MRI. This rim correlated with the histopathologic
      demonstration of a fibrous capsule in all three cases. CONCLUSION: The following
      features may be encountered in inflammatory pseudotumor: a homogeneous avascular
      appearance on CT, isointense signal on T2-weighted MRI, and the presence of a
      capsule. All these findings correlated well with histopathologic findings.

PMID- 7822556
TI  - Staging of colon carcinoma using water enema CT.
AB  - OBJECTIVE: To determine the accuracy of water enema CT (WECT) for staging colon
      carcinoma. MATERIALS AND METHODS: Thirty patients with colon cancer, diagnosed by
      barium enema and/or colonoscopy, underwent preoperative WECT. Dynamic contrast
      enhanced CT studies were performed after rectal administration of < or = 2 L
      lukewarm tap water. Images were prospectively analyzed for depth of tumor
      invasion, nodal involvement, and distant metastases by investigators blinded to
      the results of barium enema and colonoscopy. Surgical/pathologic proof was
      obtained in all cases. RESULTS: Using WECT, 23 of 30 patients were correctly
      staged. Correct staging occurred in 2 of 2 patients with Stage A, 3 of 3 patients
      with Stage B1, 6 of 9 patients with Stage B2, 1 of 2 patients with Stage C1, 5 of
      8 patients with Stage C2, and 6 of 6 patients with Stage D tumors. Of the
      patients incorrectly staged, 4 were understaged and 3 were overstaged; all were
      due to errors in predicting lymph node involvement. Sensitivity and specificity
      for evaluating nodal involvement were 60 and 79%, respectively. CONCLUSIONS:
      Water enema CT allows for accurate depiction and staging of colon carcinoma.
      Aqueous distention of the colon avoids artifacts seen with positive contrast
      agents yet allows accurate evaluation of the bowel wall and pericolonic
      structures.

PMID- 7822555
TI  - Torsion of the wandering spleen: CT and angiographic appearance.
AB  - OBJECTIVE: To seek CT and angiographic appearances that characterize torsion of
      the wandering spleen. MATERIALS AND METHODS: The CT and angiographic findings of
      two cases of preoperatively diagnosed torsion of the wandering spleen were
      reviewed, and the findings were closely compared with intraoperative and
      histopathological findings. RESULTS: Characteristic CT appearance seemed to be a
      whirled appearance formed at the medial side of the displaced spleen. The
      angiographic finding that was characteristic of the disease was a tapered and
      abruptly twisted distal splenic artery. CONCLUSION: These findings were useful in
      making the early and correct diagnosis of this rare but fulminant condition.

PMID- 7822557
TI  - Atraumatic osteolysis of the distal clavicle: MR findings.
AB  - OBJECTIVE: The purpose of this study was to describe the MRI appearance in
      atraumatic osteolysis of the distal clavicle (AODC). MATERIALS AND METHODS: We
      retrospectively evaluated MRI, medical records, ancillary diagnostic imaging
      studies and clinical course in five men and two women (mean age, 39 years) in
      whom the final clinical diagnosis of AODC was established. None of the patients
      had significant shoulder injury, but all participated in activities involving
      repetitive strain of the acromioclavicular (AC) joint. In three of these
      patients, we performed follow-up MRI (ranging from 5 1/2 to 15 months after the
      initial MRI). RESULTS: In all seven patients, signal intensity changes within the
      intramedullary portion of the distal clavicle on MRI were consistent with diffuse
      bone marrow edema. Marrow edema was most conspicuous on STIR imaging and
      occasionally could be misinterpreted as normal marrow signal patterns on spin
      echo imaging. Cortical thinning or irregularity of the distal clavicle was seen
      in six cases and tiny subchondral cysts were seen in three, corresponding to
      subtle cystic changes on shoulder radiography. Limited bone scans obtained in two
      patients showed markedly increased uptake of radiotracer at the distal clavicle
      and AC joint. Histologic examination in one case showed disruption of articular
      cartilage, subchondral cysts, and metaplastic bone formation with increased
      osteoclastic activity. Follow-up MRI in three patients who were asymptomatic
      following conservative therapy showed normalization of marrow signal intensity.
      CONCLUSION: Atraumatic osteolysis of the distal clavicle is a relatively uncommon
      but important cause of shoulder pain. Particularly when the clinical history is
      suggestive of repetitive AC joint stress, MRI of the distal clavicle should be
      examined closely for marrow edema, cortical irregularity, and cystic changes.
      Such abnormalities may be especially conspicuous when STIR imaging techniques are
      used.

PMID- 7822558
TI  - Signal, contrast, and resolution in optimized PD- and T2-weighted turbo SE images
      of the knee.
AB  - OBJECTIVE: Signal and contrast behavior, delineation of anatomical details, and
      flow artifacts were compared in dual echo SE and turbo SE (TSE) sequences.
      Results were correlated with theoretical aspects of the TSE technique. MATERIALS
      AND METHODS: A TSE sequence (TR = 3,500 ms, TEeff = 19, 93 ms, ETL = 3) and a
      conventional SE sequence (TR = 2,500 ms, TE = 20, 70 ms) were applied to 64
      patients with knee injuries. Signal intensities of anatomical structures were
      measured in regions of interest. Contrast and edge sharpness of menisci and
      posterior cruciate ligament were evaluated by three independent observers.
      RESULTS: The TSE sequence yielded similar signal and contrast behavior compared
      with SE. Visual evaluation revealed nearly equivalent contrast and edge sharpness
      of menisci and posterior cruciate ligament in proton-density (PD)-weighted TSE
      images. Contrast and edge sharpness of menisci were significantly lower in T2
      weighted TSE images. Reduced flow artifacts were found in PD- and especially in
      T2-weighted TSE images. Differences between both techniques are interpreted,
      taking into account influence of TEeff, ETL, k-space trajectory, magnetization
      transfer effects, and J-coupling. CONCLUSION: The TSE sequence yielded good image
      quality in PD-weighted, but slightly inferior quality in T2-weighted, images,
      reducing the time of acquisition by 50%.

PMID- 7822559
TI  - Celebrating Diversity in Education and Science. AADS 72nd annual session and
      exposition. San Antonio, Texas, March 11-14, 1995. Abstracts.

PMID- 7822560
TI  - Gender roles as mediators of sex differences in expressions of pathology.
AB  - This study tested the extent to which gender role attributes and gender role
      ideology account for sex differences in internally directed psychological
      distress and in externally directed deviant behavior in a random sample of 2,013
      adolescents. Results indicate that gender roles substantially mediate sex
      differences in both types of pathology: Masculine instrumental attributes reduce
      internalized distress, whereas feminine expressive attributes reduce externalized
      behavior problems. In addition, conventional gender role attitudes were
      positively related to externalizing problems among male adolescents, but were
      unrelated to pathology among female adolescents. These associations were largely
      equivalent across Black and White racial groups and across age groups (13 to 19
      years). Two alternative theoretical models linking gender roles and pathology are
      discussed.

PMID- 7822561
TI  - Assessment of psychopathy as a function of age.
AB  - The assessment of psychopathy was examined as a function of age in 889 male
      prison inmates between the ages of 16 and 69. Ratings of psychopathy were made
      with the Psychopathy Checklist (PCL), which measures 2 correlated factors. Factor
      1 describes a cluster of affective-interpersonal traits central to psychopathy.
      Factor 2 describes traits and behaviors associated with an unstable, unsocialized
      lifestyle, or social deviance. Cross-sectional analyses revealed that mean scores
      on Factor 1 were stable across the age-span; mean scores on Factor 2 declined
      with age. The prevalence of antisocial personality disorder, and, to a lesser
      extent of PCL-defined psychopathy, also declined with age. The results are
      consistent with a conceptualization of psychopathy as encompassing 2 correlated
      but distinct constructs. They also suggest that age-related differences in traits
      related to impulsivity, social deviance, and antisocial behavior are not
      necessarily paralleled by differences in the egocentric, manipulative, and
      callous traits fundamental to psychopathy.

PMID- 7822562
TI  - Social perceptions and borderline personality disorder: the relation to mood
      disorders.
AB  - We used the Structural Analysis of Social Behavior (SASB) to compare the social
      perceptions of borderline, unipolar, and bipolar-depressed inpatients. As
      predicted, borderline subjects differed from bipolar-depressed and unipolar
      subjects in their social perceptions. Borderline subjects viewed their
      relationships to their mother, hospital staff, and other patients as more hostile
      and autonomous than did mood disordered subjects. The results are discussed in
      terms of an integrative theory of borderline personality that considers the
      psychobiology of interpersonal relationships and attachment disruptions.

PMID- 7822563
TI  - A dual-task analysis of resource allocation in dysthymia and anhedonia.
AB  - Research has shown dysthymic individuals to be hyporesponsive at various stages
      of information processing, yet it is not clear whether dysthymics are deficient
      in the amount of available attentional resources for information processing or,
      instead, in the allocation of those resources. To distinguish between these
      possibilities, the authors compared dysthymics to anhedonic and normal control Ss
      during the performance of memory tasks, under conditions of varying task priority
      and difficulty. Although there were no performance differences, dysthymics and
      anhedonics exhibited a consistently smaller P300 component of the event-related
      potential. Furthermore, P300 results indicated that dysthymics and anhedonics
      responded differently from controls to variations in task demands. Thus, although
      evidence was obtained for group differences in both resource capacity and
      resource allocation strategy, the overall pattern of results is interpreted as
      favoring the latter.

PMID- 7822564
TI  - Perceptions of parental and peer attachments by women with mood disorders.
AB  - The relationship between perceptions of parental and peer attachments at various
      ages and adult mood disorders was examined in 156 women classified as having
      bipolar disorder or unipolar depression or as nonpsychiatric controls.
      Nonpsychiatric controls reported a decreased attachment to their parents over
      time, but they also reported an increased closeness to their mothers in adulthood
      following a distant adolescence. Never hospitalized, moderately depressed
      subjects showed a similar trend toward decreased relatedness, but moderately
      depressed subjects did not report reestablishment of a close relationship with
      their mothers after adolescence. Severely depressed and bipolar subjects reported
      little attachment to their mother at all ages. Bipolar subjects also reported
      little connectedness to their fathers throughout their lifespan and severely
      depressed women felt less attached than nonpsychiatric controls to peers during
      development. None of the psychiatric groups reported difficulties with parental
      overcontrol.

PMID- 7822565
TI  - Common and specific dimensions of self-reported anxiety and depression:
      implications for the cognitive and tripartite models.
AB  - The common and specific symptom dimensions of anxiety and depression proposed by
      the tripartite (L.A. Clark & D. Watson, 1991 c) and cognitive (A.T. Beck, 1976,
      1987) models were investigated in 844 psychiatric outpatients and 420
      undergraduates. Principal-factor analyses with oblique rotations performed on the
      42 items of the Beck Depression Inventory and Beck Anxiety Inventory for both
      samples revealed that there were 2 correlated factors. Depression and Anxiety.
      Second-order factor analyses of the interfactor correlation matrices indicated a
      large general distress or negative affect factor underlying the relationship
      between the 2 first-order factors. Specific depression and anxiety dimensions
      were apparent even after we controlled for negative affect. The results were
      consistent with both the tripartite and cognitive models, with the cognitive and
      motivational symptoms specific to depression and the physiological arousal
      symptoms unique to anxiety.

PMID- 7822566
TI  - Negative reactions to depressive behaviors: a communication theories analysis.
AB  - Interpersonal aspects of depression have received considerable research attention
      in the past 2 decades. This work often has been guided by J. C. Coyne's (1976b)
      interactional model of depression or P. M. Lewinsohn's (1974) social skill
      deficit theory of depression. A review of this research indicates that depressed
      people reliably experience rejection from those in their social environment and
      that depression generally is associated with impairments in social behavior.
      However, this research does not explain exactly what depressed people do to
      elicit rejection, or exactly why others react negatively to them. Research
      derived from communication theories on responsiveness, politeness, and
      expectations for nonverbal involvement illuminates the interpersonal cycle in
      depression. The role of these impairments in the cause, symptoms, course,
      subtypes, and therapy of depression is discussed.

PMID- 7822567
TI  - Dependency, self-criticism, and perceptions of socialization experiences.
AB  - This study explored the relationship of dependency and self-criticism to
      perceptions of socialization experiences using 132 bipolar, nonbipolar depressed,
      and nonpsychiatric control female subjects. After controlling for level of
      depression and diagnosis, dependency was related to a distant relationship with
      fathers during development and was marginally related to perceptions of increased
      parental attention and overindulgence. Self-criticism was related to perceptions
      of difficulties in the quality of affective bonds with fathers and peers during
      childhood and was related marginally to perceptions of increased paternal power
      and control during development. No unique socialization experiences were
      associated with high dependency and self-criticism jointly, but women with both
      dispositional tendencies were likely to be severely depressed.

PMID- 7822568
TI  - A multimethod analysis of families with a polydrug-dependent or normal adolescent
      daughter.
AB  - We compared behavioral interactions and perceived relationships in families of
      drug-dependent and normal adolescent girls. A total of 29 family triads including
      father, mother, and teenage daughter participated. L. S. Benjamin's (1974)
      structural analysis of social behavior model and methodology were used to code
      videotaped interactions and to rate self and other in perceived relationships.
      Observations of parental behavior toward their daughters did differentiate
      families of drug abusers from control families, but daughters' behavior did not.
      Parents communicated a conflictual message of both greater affirmation and
      condemnation of their daughter's autonomy. Both parents and daughters in the drug
      dependent group blamed the daughters, despite their actual behavior, for the
      family's problems. The findings are interpreted as consistent with social
      developmental and psychoanalytic theories of adolescent substance abuse as
      derailed individuation from the family.

PMID- 7822569
TI  - Subtyping major depression: a taxometric analysis.
AB  - Taxometric procedures were used to test claims for the content and latent
      structure of 5 proposed subtypes of major depression: an endogenous form,
      sociotropic and autonomous forms proposed by A. Beck (1983), a self-critical form
      proposed by S. J. Blatt (e.g., S. J. Blatt & E. Homann, 1992), and a hopelessness
      form proposed by L. Y. Abramson, G. I. Metalsky, and L. B. Alloy (1989). Analysis
      of self-reported symptom and personality profiles of 531 consecutively admitted
      outpatients with a primary major depressive diagnosis sought to determine whether
      the clinical features proposed by the respective accounts systematically covary;
      which features are central to the respective latent structures; and whether these
      structures are discrete or continuous. Clear evidence for discreteness was found
      only for the endogenous subtype. The other proposed forms lacked internal
      coherence or were more consistent with a continuous or dimensional account.

PMID- 7822570
TI  - Fear of physical sensations and trait anxiety as mediators of the response to
      hyperventilation in nonclinical subjects.
AB  - Three studies were conducted to compare the ability of a measure of fear of
      physical sensations (Anxiety Sensitivity Index; ASI) and a measure of trait
      anxiety (State-Trait Anxiety Inventory; STAI) to predict response to
      hyperventilation. In the first study subjects (N = 43) were selected who differed
      in scores on the ASI but were equated on levels of trait anxiety. Two other
      studies were conducted in which subjects (ns = 63 and 54) varied randomly on ASI
      and STAI scores. The results indicate that scores on the ASI account for a
      significant proportion of variance in the response to hyperventilation that is
      not accounted for by scores on the STAI.

PMID- 7822571
TI  - Psychopathy and conduct problems in children.
AB  - Factor analysis of a measure of psychopathy was conducted in a sample of 95
      clinic-referred children between the ages of 6 and 13 years. These analyses
      revealed 2 dimensions of behavior, one associated with impulsivity and conduct
      problems (I/CP) and one associated with the interpersonal and motivational
      aspects of psychopathy (callous/unemotional: CU). In a subset of this sample (n =
      64), analyses indicated that scores on the I/CP factor were highly associated
      with traditional measures of conduct problems. In contrast, scores derived from
      the CU factor were only moderately associated with measures of conduct problems
      and exhibited a different pattern of associations on several criteria that have
      been associated with psychopathy (e.g., sensation seeking) or childhood
      antisocial behavior (e.g., low intelligence, poor school achievement, and
      anxiety). These analyses suggest that psychopathic personality features and
      conduct problems are independent, yet interacting, constructs in children,
      analogous to findings in the adult literature.

PMID- 7822572
TI  - Unconditioned stimulus rehearsal and the retention and enhancement of
      differential "fear" conditioning: effects of trait and state anxiety.
AB  - In 2 experiments, the effect of anxiety on the cued-unconditioned stimulus (UCS)
      rehearsal phenomenon was investigated (T. Jones & G. C. L. Davey, 1990). In
      Experiment 1, postconditioning rehearsal of the unconditioned stimulus (UCS)
      resulted in an increase in conditioned response (CR) strength during extinction,
      but only in subjects with high levels of trait anxiety. An induced mood procedure
      was used in Experiment 2, and a postrehearsal increase in CR strength was found
      in subjects who had undergone induced somatic anxiety but not in subjects who had
      undergone induced worrying or who underwent a neutral induction procedure. In
      both experiments, the increase in CR strength following UCS rehearsal was
      associated with inflated ratings of the aversiveness of rehearsing the UCS. These
      results are discussed in terms of the ways in which anxiety might influence UCS
      rehearsal and facilitate physiological CRs to the conditioned stimulus.

PMID- 7822573
TI  - Affective and social-behavioral correlates of physical and social anhedonia in
      schizophrenia.
AB  - The association between scales measuring physical and social anhedonia, self
      reports of affective response to emotion-eliciting films, and role play measures
      of social skill was evaluated in patients with schizophrenia, schizoaffective
      disorder, and bipolar affective disorder. We hypothesized that patients with
      schizophrenia would report significantly greater anhedonia than the bipolar
      patients and that higher scores on the anhedonia scales would be related to
      attenuated reports of the experience of positive affect and poorer social skill.
      Patients with schizophrenia and schizoaffective disorder did not differ in
      ratings of anhedonia, but both groups had higher physical and social anhedonia
      scores than did bipolar patients. Higher scores on the physical anhedonia scale,
      but not the social anhedonia scale, were related to attenuated reports of
      positive affect following viewing of affect-eliciting films in schizophrenia
      schizoaffective disorder patients. Neither anhedonia scale was related to role
      play measures of social skill performance for any patient group.

PMID- 7822574
TI  - Dependency characteristics of partner assaultive men.
AB  - Men who had physically assaulted female partners (PA group; N = 24) were compared
      with maritally discordant nonviolent men (DNV group; N = 24) and happily married
      nonviolent men (HNV group; N = 24) on measures of dependency and related
      constructs. PA men reported higher interpersonal dependency, higher spouse
      specific dependency, and lower self-esteem than both contrast groups, but did not
      differ significantly on a measure of jealously. Data reduction indicated two
      constructs underlying these measures: perceived personal inadequacy and emotional
      investment in the primary relationship. PA men were high on both, while DNV men
      had moderate perceived inadequacy and low emotional investment and HNV men had
      low perceived inadequacy and high emotional investment. The findings support the
      clinical observation that interpersonal dependency is an important factor in the
      motivational dynamics of relationship violence.

PMID- 7822575
TI  - Depressive deficits in recognition: dissociation of recollection and familiarity.
AB  - Dysphoric and nondysphoric students (48 women and 24 men) participated in an
      experiment that was designed to separate automatic and controlled uses of memory
      in a modified recognition paradigm. First, they judged the relation of target
      words to paired words. Later they made recognition decisions on target items
      alone or in the context of the original paired item. The use of L.L. Jacoby's
      (1991) process dissociation procedure revealed depressive deficits in estimates
      of recollection but not in estimates of familiarity. The paired test improved
      recollection for all subjects and showed a trend in the direction of increased
      familiarity. These outcomes support approaches to depressive cognition that
      emphasize impaired cognitive control.

PMID- 7822576
TI  - Relationship of sociotropy/autonomy and dependency/self-criticism to DSM-III-R
      personality disorders.
AB  - Relationships between Beck's constructs of sociotropy/autonomy and Blatt's
      constructs of dependency/self-criticism and the Diagnostic and Statistical Manual
      of Mental Disorders (3rd ed., rev.; American Psychiatric Association, 1987) Axis
      II personality disorders were examined. Two measures of personality styles and a
      structured diagnostic interview for personality disorders were administered to
      138 outpatients. Significant relationships were found between both sets of
      constructs and a number of personality disorders using both categorical and
      dimensional measures of Axis II psychopathology. These relationships were
      consistent with previous theory, supporting recent conceptualizations extending
      the range of psychopathology associated with these personality styles from
      depression to the personality disorders. However, the autonomy/self-criticism
      dimension was correlated with a broader range of personality disorder traits and
      diagnoses than anticipated.

PMID- 7822577
TI  - The syntactic role of pauses in the speech of schizophrenic patients with alogia.
AB  - This study examines the relation between alogia and pausing. The authors analyzed
      the flow of speech of 17 male schizophrenic patients during an interview,
      particularly the pauses that occurred within and between syntactic clauses and
      those that occurred as the turn switched from the interviewer's question to the
      patient's response. The strongest predictor of alogia ratings was the duration of
      switching pauses; the frequency of long within-clause pauses was also
      significantly related to alogia, but the frequency of between-clause pauses
      showed a trend toward a negative relation with alogia. Words following within
      clause pauses were more likely to be content words than function words, and the
      content words were less frequent in the English language than the speaker's other
      words. This suggests that alogic patients have difficulty in word finding and in
      thought formulation, as well as a general increase in the duration of all pauses.

PMID- 7822578
TI  - Dichotic-listening measures of brain laterality in mania.
AB  - Dichotic syllable and complex tone tests were used to compare performance
      asymmetries in manic patients (n = 35) with normal controls (n = 26) and to
      determine whether there were changes in laterality with remission of the manic
      state. Relationships of performance asymmetries to treatment outcome and symptom
      features were also examined. Compared with normal controls, manic patients showed
      overall poorer accuracy, particularly for complex tones presented to the left
      ear, and they failed to show the normal left-ear (right-hemisphere) advantage for
      complex tones. Abnormal laterality for complex tones was present in patients who
      later responded to treatment but not in nonresponders. In the euthymic state,
      patients showed improved left-ear accuracy for complex tones and more normal
      perceptual asymmetry. These findings suggest that mania is associated with a
      decrement in right-hemisphere processing of complex tonal information.

PMID- 7822579
TI  - Anxiety disorders and marital quality.
AB  - This study compared perceived marital quality among couples in which neither,
      one, or both spouses met criteria for an anxiety disorder. Phobic husbands and
      their wives reported poorer marital quality than did other spouses. Husbands'
      panic disorders had similar but weaker effects on perceived marital quality, and
      wives' panic disorders predicted poor perceived marital quality by by husbands.
      Wives with generalized anxiety disorder perceived their marriages to be less
      satisfying than did other wives. The effects of husbands' generalized anxiety
      disorders were strongest in the presence of comorbid depression or alcohol or
      drug dependence but the effects of husbands' phobias and of panic disorders did
      not vary with comorbidity. Spouse concordance for phobias was related to more
      favorable marital reports, but concordance for other anxiety disorders was
      unrelated to marital quality.

PMID- 7822580
TI  - Electrodermal activity and clinical status in chronic schizophrenia.
AB  - The present study investigated the association between electrodermal
      nonresponsiveness and clinical state in schizophrenia. Sixty-three patients with
      a DSM-III diagnosis of chronic schizophrenia served as subjects. Clinical status
      was assessed using multiple measures, including age of onset, symptom severity,
      illness duration, hospitalization history, global functioning, and occupational
      functioning. Electrodermal hypoactivity was found to be associated with poorer
      functioning and a more severe form of illness. In addition, hyporesponsive
      patients displayed more conceptual disorganization and alogia.

PMID- 7822581
TI  - Childhood emotional expressions, educational attainment, and age at onset of
      illness in schizophrenia.
AB  - This study examined the relation between preschizophrenic subjects' facial
      expressions of emotion in childhood home movies and two criterion variables:
      educational level (highest grade completed) and age at onset of illness. Earlier
      research suggest that premorbid affective blunting is associated with an earlier
      onset of illness and poorer prognosis in schizophrenia. It was, therefore,
      predicted that lower rates of both positive and negative facial expressions would
      be associated with lower levels of educational attainment and earlier age at
      onset of illness. The results indicated that childhood emotional expressions were
      not associated with educational level but were linked with age at onset.
      Preschizophrenic subjects who showed lower rates of negative emotion during late
      childhood/adolescence were younger at illness onset. Findings are discussed in
      light of previous reports linking affective symptoms with better prognosis in
      schizophrenia.

PMID- 7822582
TI  - Priming effects in schizophrenia: associative interference and facilitation as a
      function of visual context.
AB  - Irrelevant stimuli that flank a fixated target may cause either facilitation or
      interference with target classification. Twenty schizophrenic patients, 20
      depressed control patients, and 20 normal control subjects were compared on a
      flanker priming task that involved the linear display of a target surrounded by
      two flanking letters or digits. Choice reaction time between letter and digit
      targets was examined as a function of flanker condition and onset asynchrony
      between flankers and target. Facilitative priming occurred only with prior
      exposure of flankers compatible with the response required and was greater in
      degree with schizophrenic and depressed than with normal subjects. Interference
      from flankers incompatible with the response required less among schizophrenics
      than among other groups. Several different processes may be involved in the
      inhibition of irrelevant information by schizophrenics.

PMID- 7822583
TI  - Smoking outcome expectancies: factor structure, predictive validity, and
      discriminant validity.
AB  - Recent models of addiction posit that drug outcome expectancies are influential
      determinants of drug use. The current research examines the dimensional
      structure, predictive validity, and discriminant validity of expectancies for
      cigarette smoking in a prospective study. There was a good fit between the factor
      structure of the Smoking Consequences Questionnaire and the observed data. In
      addition, the internal consistency of each scale was satisfactory. Moreover,
      there was considerable evidence for the predictive and discriminant validity of
      expectancies. Expectancies of positive outcomes (positive reinforcement, negative
      reinforcement, and appetite-weight control) predicted withdrawal severity.
      Negative reinforcement expectancies and expectancies of negative consequences
      predicted cessation success. Predictive relations remained significant after
      controlling for related constructs: negative affect, stress, and dependence
      measures.

PMID- 7822584
TI  - Effects of cue exposure and deprivation on cognitive resources in smokers.
AB  - This research examines the effects of manipulations designed to induce an urge to
      smoke on cognitive resources. Two cue-exposure experiments were conducted in
      which current smokers' reported urge to smoke and cognitive resources, as
      measured by a secondary reaction time (RT) probe, were assessed. In each study,
      subjects came to the laboratory twice, once while deprived of smoking for 12 hr
      and once when they were nondeprived. During each session, subjects were exposed
      to both smoking and control cues. Results indicated that experimental
      manipulations designed to elicit a strong urge to smoke led to an increase in
      self-reported urge to smoke and a decrease of available cognitive resources, as
      measured by RT. In addition, these 2 measures were significantly correlated.
      These data, in conjunction with previous findings using alcohol-dependent
      subjects (M. A. Sayette et al., 1994), lend support to the validity of RT as an
      objective measure of the effects of cue exposure on cognitive resources.

PMID- 7822585
TI  - Patients' and informants' reports of personality traits during and after major
      depression.
AB  - The influence of major depression on patients' and informants' reports of
      personality traits was examined using the Structured Interview for DSM-III
      Personality Disorder, both before and after successful antidepressant or placebo
      treatment (N = 58). According to patients' reports, Cluster A and C traits
      decreased significantly from pre- to posttreatment, but Cluster B traits were
      unchanged, excluding an increase in histrionic traits. According to informants'
      reports, Cluster A and B traits did not change from pre- to posttreatment, but
      Cluster C traits decreased significantly after treatment, not including passive
      aggressive traits. Moreover, informants generally reported much higher levels of
      maladaptive personality traits than patients themselves. These results suggest
      that informants should be used in future research on personality disorders until
      better assessment techniques are developed.

PMID- 7822586
TI  - An in vivo assessment of physiological arousal in posttraumatic stress disorder.
AB  - The present study measured physiological function (heart rate [HR], systolic
      blood pressure [SBP], diastolic blood pressure [DBP], sublingual temperature, and
      respiration rate) in a nonresearch setting--the medical triage area of a large
      Veterans Affairs Medical Center while patients were awaiting physical
      examination. Subjects were 32 Vietnam veterans with combat-related posttraumatic
      stress disorder (PTSD) and 26 Vietnam-era veterans with no combat experience.
      Results indicated that PTSD veterans had significantly higher HR, SBP, and DBP,
      but not sublingual temperature or respiration rate. These data support the
      position that individuals with PTSD do indeed demonstrate higher levels of
      cardiovascular arousal across settings.

PMID- 7822587
TI  - Hemispheric laterality and memory bias for threat in anxiety disorders.
AB  - The authors examined auditory perceptual asymmetries and explicit memory biases
      for threat in patients with panic disorder and generalized anxiety disorder
      relative to healthy control subjects. They did not find a greater explicit memory
      bias for threat in the anxiety patients. However, explicit memory biases for
      threat were associated with perceptual asymmetry scores; patients with a greater
      right-ear (left hemisphere) advantage exhibited an explicit memory bias for
      threat material, whereas patients with a lower right-ear advantage displayed
      apparent cognitive avoidance of threat material. Memory for threat words was
      unrelated to perceptual asymmetry in healthy control subjects. These findings
      suggest that neuropsychological variables may partly determine the degree to
      which anxiety patients process threatening stimuli.

PMID- 7822588
TI  - Neuropsychological performance on tests of frontal-lobe functioning and
      aggressive behavior in men.
AB  - The authors tested the relationship between frontal-lobe functioning and physical
      aggression in young men in a laboratory setting. Seventy-two men completed two
      putative neuropsychological measures of frontal-lobe functioning--the Self
      Ordered Pointing (SOP) Task and the Conditional Association Task (CAT)--and an
      abbreviated version of the Wechsler Adult Intelligence Scale--Revised. Aggression
      was measured with a modified version of the Taylor reaction-time aggression
      paradigm, whereby electric shocks are received from and administered to a
      fictitious "opponent" during a competitive task within high- and low-provocation
      conditions. High and low provocation levels were defined by the intensity of
      shocks the subjects received. Results demonstrated that aggression was
      significantly related to performance on the CAT but not the SOP. The findings are
      discussed with regard to the hypothesized link between frontal-lobe functioning
      and aggressive behavior.

PMID- 7822589
TI  - Relation of media exposure to eating disorder symptomatology: an examination of
      mediating mechanisms.
AB  - Although investigators have postulated that the thin ideal for women espoused in
      the media is related to the high rates of eating disorders among females, little
      research has examined the relation between media exposure and eating pathology.
      This study assessed the relation of media exposure to eating disorder symptoms
      and tested whether gender-role endorsement, ideal-body stereotype
      internalization, and body satisfaction mediated this effect. In data from 238
      female undergraduates, structural equation modeling revealed a direct effect of
      media exposure on eating disorder symptoms. Furthermore, mediational linkages
      were found for gender-role endorsement, ideal body stereotype internalization,
      and body satisfaction. The results support the assertion that internalization of
      sociocultural pressures mediate the adverse effects of the thin ideal.

PMID- 7822590
TI  - The future of homoeopathy and other complementary therapies as part of the
      British National Health Service.

PMID- 7822591
TI  - Philosophy, biology and mental disorder.
AB  - The biological model has become the touchstone for our thinking on mental
      disorder. The success of this model has relegated opposing views to the
      sidelines. Philosophers have been considering the nature of mind for well over
      2500 years, and their speculations may provide a useful antidote to the creeping
      reductionism and materialism inherent in simple biology. The emphasis in
      philosophical theories is on the nature of the mental and the structuring role of
      the mind in our construction of reality. This paper focuses on three
      philosophers, Kant, Heidegger and Husserl, and their contribution to our
      understanding of the nature of psychopathology. The biological theory is re
      examined from the differing perspectives offered, and some of the assumptions on
      which it is based are subjected to criticism. The emphasis, found in the
      philosophical theories, on the mental as opposed to the physiological aspects of
      the mind, is considered to be more germane to the practical and therapeutic
      concerns of those who must deal with the dis-ease of mental disorder.

PMID- 7822592
TI  - Depression and issues of control among elderly people in health care settings.
AB  - This descriptive study investigated the relationship between both demographic
      characteristics and type of health care setting and elderly people's attributions
      for control, functional status, mood, type of helplessness, and perception of
      self-efficacy. Results of the study demonstrate that elderly people in long-term
      care settings are more vulnerable to experiencing learned helplessness and
      depression than elderly people in acute or rehabilitation settings. The findings
      indicate that the critical period for the development of learned helplessness and
      depression is for subjects with a length of stay of 7 weeks to 6 months. The
      study supports other research which concludes that depression in elderly people
      is better explained by the original learned helplessness theory rather than being
      related to attributions about the cause of loss of control.

PMID- 7822593
TI  - Nurses' attitudes towards older people: a comparison between nurses working in
      acute medical and acute care of elderly patient settings.
AB  - Drawing on a sample of 76 nurses from two health authorities working in acute
      medical or acute care of elderly patient wards, a quantitative approach was taken
      to compare their attitudes. A questionnaire which identified possible predictors
      of attitude, knowledge about older people (via a modified Palmore's Facts on
      Ageing Quiz) and attitudinal disposition (via Kogan's Old People Scale) was
      distributed. Results indicated a statistically significant difference (P = 0.03)
      in attitudes, with elderly care nurses scoring more favourably. Factors which
      might explain such a finding are identified, namely post-basic gerontological
      education, age of respondent and knowledge of older people, and their relative
      influences discussed. Conclusions are based on the premise that any variation
      based on specialist area is unacceptable since care of older people is now within
      every nurse's remit, and suggested interventions are outlined.

PMID- 7822594
TI  - The meal situation in geriatric care--intentions and experiences.
AB  - Meals in geriatric institutions are often served in a dining room. The elderly
      patients--endowed with their socialized table manners and diet habits--who enter
      this milieu are affected by diseases and handicaps, reducing their ability to
      eat. In the present study individual patients' meals in geriatric care
      institutions were studied with respect both to nursing staffs' intentions and
      assessments of patients, as well as to those patients' experiences and the amount
      of influence they expected to have. The research approach was ethnographic.
      Eighteen newly admitted, mentally orientated patients and their primary enrolled
      nurses were allocated. The results indicated that the idea of both the nurses and
      the elderly patients was to reach a meal situation that was as natural and
      independent as possible. Compared with the elderly patients, the nursing staff
      had broader standards for acceptable table manners, and carried out collective
      dining of all 18. The elderly patients strove to behave in accordance with their
      standards and suffered because of their own limited eating competence and the
      experience of other patients' problems. The elderly patients avoided expressing
      their needs, and some enrolled nurses thought they were prying if they asked
      questions about such issues. These different, culturally dependent, perceptions
      resulted in care that was not congruent with the needs of the elderly patients.

PMID- 7822595
TI  - The subjective and psychosocial nature of breathlessness.
AB  - Dyspnoea, also referred to as breathlessness, is a concern of nurses in most
      clinical settings. Nursing interventions are directed toward preventing or
      treating dyspnoea in a timely manner. Even though dyspnoea is a common phenomenon
      found in clinical settings and discussed in the literature, it has not been added
      formally to the list of diagnoses developed by the North American Nursing
      Diagnosis Association, most likely because it is an isolated, observable sign.
      However, breathlessness, the related construct, is a distinctly different
      phenomenon from dyspnoea. The terms dyspnoea and breathlessness are used
      interchangeably in the literature. Traditionally, dyspnoea is defined as
      difficult or laboured breathing observable to another person. Breathlessness is
      the subjective feeling of laboured breathing with and without dyspnoea and/or
      abnormal pulmonary functions. These authors submit that the nursing diagnosis of
      breathlessness consists of two essential defining criteria, the subjective
      feeling of difficulty in breathing and anxiety, in the presence or absence of
      dyspnoea and/or abnormal pulmonary functions. A biopsychosocial model is
      presented to guide research and nursing care for individuals who experience
      breathlessness.

PMID- 7822596
TI  - A victimization assessment tool: instrument development and clinical
      implications.
AB  - Although most health care providers now recognize the importance of crisis
      intervention, support, and/or treatment for survivors of violence and abuse, such
      care is compromised unless early detection becomes a routine part of intake and
      assessment protocols in nursing and other facets of health care. This paper
      describes the development of a tool to assist nurses and other primary care
      providers with routine assessment for victimization in diverse health and mental
      health settings. It includes outcomes of preliminary validity and reliability
      studies, and concludes with suggestions for use in clinical work with
      victims/survivors of abuse in an era of increasing international concern
      regarding the health implications of violence.

PMID- 7822597
TI  - The psychosocial needs of patients who have attempted suicide by overdose.
AB  - This is an exploratory study using qualitative methods to investigate and
      highlight psychosocial needs as perceived by individuals who have survived an
      attempted suicide through self-poisoning. Respondents consisted of a convenience
      sample of six people (three male and three female). Data were collected through
      interviews and analysed using the principles of content analysis devised by Field
      and Morse. Major needs identified include the need to be loved, the need to
      maintain a high level of self-esteem, the need to have control of one's life and
      the need to be supported. Findings indicate that these needs are not being met by
      the current mental health care delivery system. In addition, nurses must begin to
      pay greater attention to assessment and planning of care for this group of
      patients. A wider use of psychosocial therapies such as crisis intervention and
      family therapy are urgently required. Above all there is a need for more in-depth
      understanding and improved communication with patients who have attempted suicide
      by self-poisoning.

PMID- 7822598
TI  - Nurses' responses to patient anger: from disconnecting to connecting.
AB  - Caring for angry patients can be a threatening experience. Grounded theory
      research was used to explore female nurses' reactions and feelings as the
      recipients of patient anger. The data were collected by interviewing nine female
      registered nurses in two hospitals in south-western Nova Scotia. The participants
      were asked to discuss their feelings and responses to an intense encounter with
      an angry patient. Anger was defined as a multi-dimensional concept with negative
      cogitations. The concept of self-efficacy emerged as the major area of concern
      for the participants. The findings suggest that when the threat to self was high,
      nurses managed anger situations by disconnecting from the angry patient. Low or
      controllable threats were generally managed by connecting with the angry patient.

PMID- 7822599
TI  - Monitoring the pressure sore problem in a teaching hospital.
AB  - During 1989 and 1990 a series of three prevalence surveys were undertaken in a
      West Midlands teaching hospital to identify the numbers of patients at risk of
      developing pressure sores and the actual number of patients with pressure sores,
      prior to the purchase of pressure relieving equipment. A further survey was
      undertaken in January 1993 to examine any improvement in pressure sore prevention
      strategies and in the care of those with established pressure sores. All in
      patients were assessed using the Waterlow score. Full details of all pressure
      sores and any pressure relieving equipment in use was recorded. The findings were
      compared with those of the first survey in 1989. The prevalence for 1989 was
      8.77%, and this had reduced slightly to 7.9% in 1993. There was no significant
      difference in these figures. However, in 1989 35 patients had 64 pressure sores
      and in 1993 32 patients had 46 pressure sores. There was a significant reduction
      in the actual numbers of pressure sores. There was no significant difference in
      the grades of sores and the sacrum was the most frequent position in both
      surveys. The survey showed an improvement in the management of established
      pressure sores. There was little change in the patient populations with respect
      to the degree of risk of pressure sore development. Using the Waterlow score, the
      numbers of patients found to be in the no risk, at risk, high risk and very high
      risk categories remained remarkably stable. These surveys will continue to
      provide a basis for selecting pressure relieving equipment.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7822600
TI  - The superiority of rectal thermometry to oral thermometry with regard to
      accuracy.
AB  - Electronic oral thermometry is performed routinely in most medical centres. From
      the studies available on this subject it seems difficult to find any
      documentation for this practice. We have conducted clinically controlled studies
      in which the accuracy of electronic oral thermometry (CRAFTEMP and TERUMO WCT)
      and that of electronic rectal thermometry (TERUMO WCT) were tested. Rectal glass
      mercury thermometry was used as a reference method. Two studies were designed. In
      study 1, 184 patients (72 women, 112 men), median age 70 (18-95) years were
      investigated. In study 2, 91 patients (41 women, 50 men), median age 59 (18-96)
      years were investigated. Electronic oral thermometry was found unacceptably
      inaccurate under daily routine conditions. Electronic rectal thermometry was
      found to be accurate. Calculations of mean temperature difference between
      reference measurements and test measurements (mean +/- SD) were found to be:
      routine oral CRAFTEMP at 0.70 +/- 0.50 degrees C, optimum oral TERUMO WCT at 0.75
      +/- 0.74 degrees C, routine rectal TERUMO WCT at 0.08 +/- 0.26 degrees C and
      optimum rectal TERUMO WCT at 0.02 +/- 0.17. In the screening procedure for fever
      oral thermometry showed low sensitivity (routine CTAFTEMP 0.47 and optimum TERUMO
      WCT 0.59) whereas rectal thermometry showed high sensitivity (routine TERUMO WCT
      0.74 and optimum TERUMO WCT 0.91). It was concluded that rectal thermometry must
      be preferred to oral thermometry for daily routine measurements.

PMID- 7822601
TI  - Testicular cancer health education: an integrative review.
AB  - Cancer of the testis is the most common malignancy in men between the ages of 15
      and 35, yet it is one of the most curable cancers. The optimistic prognosis that
      results from early detection and treatment of testicular cancer underscores the
      critical need for teaching testicular self-examination (TSE). However, an
      integrative review of the health education literature suggests that the men most
      susceptible are virtually unaware of the symptoms of testicular cancer and how to
      detect them. Although educational materials have been available, very little
      intervention research has been published on testicular cancer. The literature to
      date has focused on the pyschosocial factors associated with the practice of TSE
      and increasing knowledge of testicular cancer. Although an important beginning
      step, knowledge of testicular cancer alone as a preventive health behaviour is
      not sufficient if young men either do not know how to do the examination on their
      own testicles or do not believe it is important to them. Nurses should
      incorporate health education for testicular cancer and TSE in the delivery of
      routine primary health care. Furthermore, future research should aim to (a)
      increase knowledge through the educational curricula of high schools and colleges
      by use of video presentations, (b) examine the efficacy of using silicone models
      to ensure that men can be trained to detect the symptoms of testicular cancer,
      and (c) study compliance with recommendations to perform TSE.

PMID- 7822602
TI  - The function of home visits in maternal and child welfare as evaluated by service
      providers and users.
AB  - This study looks at how public health nurses and clients of maternal and child
      welfare clinics evaluate the function and meaning of home visits. Another concern
      is with the options available to the service user. The data were collected during
      November and December 1992 from a total of 203 health centres across Finland;
      responses were obtained from 263 public health nurses and 323 clients. The
      results are presented in the form of frequencies, percentages and cross
      tabulations. According to the results, the clients felt that the most important
      function of home visits was to have a competent professional examination of the
      newborn. They also attached much importance to the information function, i.e.
      learning about the growth and care of small children. The public health nurses,
      on the other hand, felt that the most important function of home visits was to
      support and encourage parents and to ensure the continuity of care. The
      advantages of meeting in the client's home environment were equally stressed by
      both sides. By contrast, clients and public health nurses had very different
      views on the options available to the client. Almost all nurses said that the
      client can freely choose between home visits and visiting the clinic; however,
      only about half the clients felt they could choose the service they best
      preferred.

PMID- 7822603
TI  - Student nurses' involvement with death: the image and the experience.
AB  - A qualitative study of student nurses' images of nursing revealed that features
      related to death were prominent in both entry and experience-mediated images.
      These features appeared in entry images as part of 'the bad' of nursing and were
      affirmed in this respect through experience. However, mediated through students'
      encounters with reality, death-related experiences also acquired characteristics
      of 'the good'. The 'involvement' entailed in caring for the dying represented a
      poignant but emotionally draining aspect of students' clinical experiences.
      Regardless of the degree of accuracy of students' entry images, the 'knowing'
      that came through experience made adjusting to death-related encounters a
      particular challenge for students. A clear implication was the need for effective
      guidance and support to be provided by the system and by individual members of
      teaching and clinical staff.

PMID- 7822604
TI  - Integrating what is taught with what is practised in the nursing curriculum: a
      multi-dimensional model.
AB  - The discrepancy between nursing as it is taught in the classroom (theory) and
      nursing as it is experienced by students in the clinical setting (practice) has
      long been a source of concern to teachers, practitioners and learners. This paper
      provides an overview of the literature on the theory-practice gap, exploring some
      of the many reasons cited for its existence as well as suggested ways of bridging
      the gap. Drawing upon the findings, a comprehensive and multi-dimensional model
      designed to integrate theory and practice of nursing is proposed for use by
      curriculum planners. Fundamental to the model is the notion of collaboration
      between education and service staff at all stages of the curriculum process. The
      model highlights eight key areas for the curriculum team to consider: the
      curriculum model to be used, sequencing of taught content and clinical practice,
      the content of the course, teaching methods to be used, assessment criteria, the
      role of tutors in the learning process, the contribution of service staff, and
      the influence of the hidden curriculum. It is argued that only through such a
      comprehensive model can integration of theory and practice within the curriculum
      be achieved. Adoption of the model, however, will require considerable individual
      and organizational commitment.

PMID- 7822605
TI  - The implementation of problem-based learning: changing pedagogy in nurse
      education.
AB  - Problem-based learning (PBL) employs approaches to teaching and learning in nurse
      education that develop meaningful links between theory and practice. The adoption
      of such approaches, however, may require changes in pedagogical beliefs and
      practices which reflect a student-centred approach to teaching and learning. This
      paper focuses on a group of volunteer nurse educators (n = 14) who attended a 7
      month professional development programme centred on introducing pedagogical
      changes when adopting PBL. From this group, three nurse educators participated in
      an in-depth study which aimed to examine the processes of conceptual change
      associated with adopting PBL as part of alternative teaching strategies. These
      three participants held common concerns about the changes required to their
      current teaching practices when moving to a new pedagogical approach. On
      completion of the programme, varying degrees of change in existing instructional
      practices were evident. This change was found to result from engaging educators
      in reflection about practice, providing opportunities to implement the new
      approaches on a trial basis, and providing feedback and support throughout the
      change process.

PMID- 7822606
TI  - When your patient is silent.
AB  - In the process of caring for patients, nurses encounter patients who are silent.
      A number of problems may arise when silence occurs in an interpersonal situation.
      Among these problems is the different meanings that silence may have from culture
      to culture. This paper describes the meaning that silence may have across
      cultures and delineates guidelines for the nurse in responding to the patient who
      is silent.

PMID- 7822607
TI  - Making anthropology clinically relevant to nursing care.
AB  - Transcultural nursing is generally seen as the interface between anthropology and
      nursing. A prime objective of transcultural nursing has been the translation of
      concepts from anthropology and nursing into the nursing process to guide a
      culturally informed clinical practice. To date, there has been a general
      inability of transcultural nursing to operationalize the concept of culture to
      develop culturally competent clinicians; that is, nurses who are capable of
      knowing, utilizing, and appreciating the effects of culture in the resolution of
      an individual, group, community, and/or family problem. A model of transcultural
      nursing is described, for incorporating the concept of culture into patient care.
      It includes the concepts of cultural brokerage, simultaneous dual ethnocentrism,
      multiple clinical realities, the patient as cultural informant, and cultural
      assessment of patient views of clinical reality. The problems of making
      anthropology and transcultural nursing clinically relevant through the
      transcultural nursing model are presented and methods are recommended for
      addressing such problems.

PMID- 7822608
TI  - The strengths and weaknesses of quantitative and qualitative research: what
      method for nursing?
AB  - The overall purpose of research for any profession is to discover the truth of
      the discipline. This paper examines the controversy over the methods by which
      truth is obtained, by examining the differences and similarities between
      quantitative and qualitative research. The historically negative bias against
      qualitative research is discussed, as well as the strengths and weaknesses of
      both approaches, with issues highlighted by reference to nursing research.
      Consideration is given to issues of sampling; the relationship between the
      researcher and subject; methodologies and collated data; validity; reliability,
      and ethical dilemmas. The author identifies that neither approach is superior to
      the other; qualitative research appears invaluable for the exploration of
      subjective experiences of patients and nurses, and quantitative methods
      facilitate the discovery of quantifiable information. Combining the strengths of
      both approaches in triangulation, if time and money permit, is also proposed as a
      valuable means of discovering the truth about nursing. It is argued that if
      nursing scholars limit themselves to one method of enquiry, restrictions will be
      placed on the development of nursing knowledge.

PMID- 7822609
TI  - Unlimited liability? Emotional labour in nursing and social work.
AB  - At the heart of the 'new nursing' is an emphasis on developing a close, holistic
      relationship between nurse and patient. Through this not only will healing be
      facilitated, and patients be encouraged to take responsibility for their own
      health, but the nurse will be placed firmly at the centre of the network of
      health professionals. Individual practitioners and the profession as a whole will
      achieve a clearer and more satisfying mission. This casting of the nurse as
      pivotal enabler parallels attempts to systematize social work theory and practice
      in the 1970s, and many common intellectual sources on relationship-building are
      used. But what are the supposed characteristics of the 'good relationship'? The
      paper argues that, while the new nursing endeavours to emphasize the social
      context of patients, health and illness, much of the psychotherapeutic literature
      called in support is essentialist: the social world is treated as a hindrance to
      the goal of 'authenticity'. Thus acquired professional knowledge and skills are
      devalued. Added to the potential of this for personal stress are risks for the
      profession itself. In circumstances of permanent financial pressure,
      foregrounding hard-to-measure criteria of success, like the quality of
      relationships, is very hazardous.

PMID- 7822610
TI  - Approaches to the problem of respondent attrition in a longitudinal panel study
      of nurses' careers.
AB  - Longitudinal panel studies have several distinct methodological and analytical
      advantages over cross-sectional studies for gaining an understanding of nurses'
      careers and developing strategies to facilitate retention. Panel studies do,
      however, present the researcher with a number of substantial challenges if
      maximum potential is to be achieved from the investment of time and resources
      that such studies entail. Respondent attrition at successive phases of data
      collection, for example, is a major problem, often with the consequence that
      respondents are not representative of the study group as a whole. This paper
      discusses reasons for choosing a longitudinal panel design for a programme of
      research into careers of midwives and nurses. The way in which the problem of
      respondent attrition has been approached in one of the projects in the programme,
      that focusing on the careers of registered general nurses, is then described.

PMID- 7822611
TI  - Nurses' creativity, tedium and burnout during 1 year of clinical supervision and
      implementation of individually planned nursing care: comparisons between a ward
      for severely demented patients and a similar control ward.
AB  - The aim of this study was to study creativity and innovative climate, tedium and
      burnout among the nurses on two wards during 1 year of systematic clinic
      supervision combined with the implementation of individualized care on an
      experimental ward (EW) for severely demented patients, as compared with a similar
      control ward (CW). EW nurses had systematic clinic supervision and each patient
      had his/her nursing care carefully planned, documented and evaluated. The
      intervention was evaluated by means of the Creative Climate Questionnaire,
      Burnout Measure and the Maslach Burnout Inventory. Creativity and innovative
      climate improved significantly among the EW nurses (n = 19) in eight out of 10
      factors during the year of intervention while there was no change on the control
      ward (n = 20). Tedium and burnout decreased significantly among the EW nurses
      while no change was seen in this respect among the CW nurses. It seems reasonable
      to assume that systematic clinical supervision and individualized planned care
      decreases the negative outcome of stress caused by the psychological burden
      imposed by nursing care. It also increases nurses' creativity, which, in turn,
      may benefit patient care. The findings of this study point to the necessity for a
      support system that focuses on the work itself, i.e. the nursing care.
      Individualized planned care and systematic clinical supervision may offer this
      kind of support.

PMID- 7822612
TI  - A staff development programme to support the incorporation of the McGill model of
      nursing into an out-patient clinic department.
AB  - In order to adopt a nursing model as a framework for professional practice in an
      out-patient department of a paediatric tertiary care hospital, a staff
      development programme was instituted. The nursing model chosen was the McGill
      model of nursing, which emphasizes the complementary role of nursing and focuses
      on people's health, strengths and potentials. Staff development initially
      consisted of a journal club and clinic nurses were exposed to such concepts as
      family, coping, and health. As the nurses acquired theoretical knowledge, the
      staff development programme was concerned with applying this knowledge to
      clinical situations. As well as the nursing in-service training, clinical
      supervision with small groups of nurses was instituted. A study showed that staff
      development helped nurses to build a larger repetoire of family nursing skills.
      The nursing role in the department evolved. Nurses developed a more professional
      practice and provided health services which were complementary to those offered
      by other health professionals.

PMID- 7822613
TI  - A comparative analysis of Orem's self-care model and Peplau's interpersonal
      theory.
AB  - The process of choosing a nursing model or theory to guide one's clinical
      practice, curriculum development or theoretical framework for research can be
      facilitated by analysis of and comparison of existing theories, with each other
      and then with one's personal philosophies. This paper summarizes the major
      concepts and assumptions of Dorothea Orem's self-care model and Hildegard
      Peplau's interpersonal theory, and then compares the two for similarities and
      differences in their origins of theory development, meanings related to nursing
      metaparadigm concepts, logical adequacy, usefulness and generalizability,
      parsimony and testability.

PMID- 7822614
TI  - The measurement of nurse performance and its differentiation by course of
      preparation.
AB  - This paper addresses the concept of nurse performance, its measurement and its
      differentiation by programme of preparation. It is evident from the research
      conducted to date that a variety of methodologies have been used to explore and
      compare nurse performance. The process of direct observation, however, has been
      selected to a lesser degree, and it is argued that its potential has yet to be
      realized. Further, in recognition of the methodological challenges inherent
      within research of this nature it is suggested that nurse performance should be
      explored from a variety of perspectives, using a multi-method research design.
      Significantly, educational preparation as a potential discriminator of
      performance has been explored only to a limited extent and studies carried out in
      the United States predominate. In view of recent nurse education changes in the
      United Kingdom and the introduction of Project 2000, empirical work comparing
      outcomes of the different courses of pre-registration preparation is urgently
      required. The authors are currently engaged in a comparative study of outcomes of
      pre-registration nurse education programmes funded by the English National Board
      for Nursing, Midwifery and Health Visiting. This paper draws upon the literature
      reviewed to date.

PMID- 7822615
TI  - Expert: a discussion of the implications of the concept as used in nursing.
AB  - The concept 'expert' has become common in the nursing literature since Benner's
      (1984) work more than a decade ago. Whilst the term has a common meaning, it is
      apparent that when used in nursing it refers to a multitude of attributes and
      lacks clear definition. This paper uses the strategy for concept analysis
      developed by Walker & Avant (1988) to seek an operational definition for the
      concept of 'expert', and suggests the defining attributes of: possession of a
      specialized body of knowledge and skill; extensive experience in a field of
      practice; highly developed levels of pattern recognition, and acknowledgement by
      others. These are discussed in relation to nursing practice and the circumstances
      under which the concept is used. Development of cases is carried out to exemplify
      the concept, and the antecedents and consequences of the attributes are
      discussed, suggesting that the concept lacks clarity, both in conceptualization,
      and in use. A first definition of the concept is posed to open debate concerning
      the relevance of the term for the future. The conclusions reached suggest that
      whilst an operational definition is unlikely to be found, because of the problems
      of definition and measurement, it is possible, through various strategies, to
      recognize expert practice and use it to further develop nursing. Furthermore, it
      is likely to become increasingly important to recognize and reward expert
      practitioners, given the political and economic constraints in health care today.

PMID- 7822616
TI  - First International Conference for Clinical Nurse Specialists on the theme
      'clinical nurse specialism: the way to advanced nursing practice'. The Albert
      Hall, Nottingham, England, 16-19 May 1994, organized by Nursing Times Open
      Learning and Nursing Times.

PMID- 7822617
TI  - In the middle: department heads.

PMID- 7822618
TI  - Public policy. The cost of clinical preventive services.

PMID- 7822619
TI  - The nurse executive. The NMDS is a trend, not a fad.

PMID- 7822620
TI  - Professional practice. A home of their own.

PMID- 7822621
TI  - Research. Selection of a research instrument: revisiting issues.

PMID- 7822622
TI  - A mandate for nursing education leadership: change.
AB  - Changes occurring in both the internal and external environments are causing the
      role of the nurse education executive to undergo a major revolution. Health care
      reform, and numerous other events in society, are causing organizations,
      corporations, and states to experience an unprecedented rate of change to
      redesign administrative and work group structures and functions, and to realign
      decision making. Because of the complexity and magnitude of change, it is
      imperative that faculty and administration design the work of the organization to
      prevent duplication of effort and be active, innovative, and creative in their
      respective areas of responsibility. The nurse education executive's challenge is
      to be prepared to lead change and to manage rapid change in an ambiguous and
      flexible environment.

PMID- 7822623
TI  - Role socialization of graduating student nurses: impact of a nursing practicum on
      professional role conception.
AB  - This study examined graduating student nurse role conception changes that
      occurred during a concentrated clinical preceptorial. A Nursing Role Conceptions
      Questionnaire was administered to nursing students before (n = 44) and
      immediately after (n = 41) a 4-week Nursing Practicum; to the students' staff
      nurse clinical teaching associates (n = 34); and to nursing program faculty (n =
      18). Respondent perceptions of ideal nursing behaviors and actual nursing
      behaviors within three major nursing roles (professional, service, and
      bureaucratic) were identified and differences between ideal and actual scores
      (role discrepancy) were calculated. Findings showed that student role orientation
      in selected areas changed from a faculty role orientation to a staff nurse role
      orientation over the 4-week period. The Practicum seemed to effectively
      facilitate role socialization of graduating student nurses into the work setting,
      easing the necessary transition from education to practice.

PMID- 7822624
TI  - Graduate education for nurse practitioners: are advanced degrees needed for
      practice?
AB  - Although the number of master's prepared nurse practitioners has expanded in the
      last 30 years, few master's level behaviors seem to be incorporated into the
      role. This study compared both actual and ideal role behaviors of master's and
      non-master's prepared nurse practitioners. These behaviors included the technical
      behaviors that all nurse practitioners should perform and master's level nursing
      behaviors. Two hundred state-certified nurse practitioners were mailed
      questionnaires asking them to identify their actual and ideal role behaviors. The
      results showed no difference in the actual role behaviors performed by both
      groups. In terms of ideal role behaviors, non-master's prepared nurse
      practitioners rated the majority of the technical and master's level behaviors
      higher than master's prepared nurse practitioners. In light of the upcoming
      changes in our health care system and the potential demand for more nurse
      practitioners, this study questions the need for all nurse practitioners to be
      educated at the master's level.

PMID- 7822625
TI  - Professionalism and the evolution of nursing as a discipline: a feminist
      perspective.
AB  - The evolution of nursing knowledge and nursing as a practice discipline has been
      stunted by the quest for professionalism. Liberal and socialist feminist theory
      clarifies the hazards inherent in the masculine institution of professionalism
      for a predominately female discipline. Socialist feminist theoretical
      perspectives facilitate a vision of nursing that includes altering social
      structure such that caring is valued.

PMID- 7822626
TI  - Effects of experimenter and mother presence on the attentional performance and
      activity of hyperactive boys.
AB  - The attentional performance, activity, and off-task behavior of hyperactive boys
      with and without conduct problems and normal boys were compared on a cancellation
      task under three conditions: when performing the task alone, with mother present,
      and with experimenter present. Results indicated that both the hyperactive groups
      achieved poorer attentional scores than normal subjects in the alone and mother
      present conditions, but improved in the experimenter present condition. The
      performance of the hyperactive boys with conduct problems was particularly
      affected by this condition. The activity and off-task behavior scores of both the
      hyperactive groups were higher than controls in all conditions, although the
      hyperactive boys with conduct problems decreased in off-task behavior when the
      experimenter was present. Attention and behavior scores were not significantly
      correlated. The implications of these findings for assessment of hyperactivity,
      and the role of noncompliance in the attentional behavior of hyperactive
      children, are discussed.

PMID- 7822627
TI  - Differential predictive value of parents' and teachers' reports of children's
      problem behaviors: a longitudinal study.
AB  - This study investigated the prediction of signs of disturbance in 946 children
      originally aged 4 to 11 years from the general population across a 6-year period.
      Parents' and teachers' ratings obtained via the Child Behavior Checklist (CBCL)
      and Teacher's Report Form (TRF) were tested as predictors of (a) academic
      problems, (b) school behavior problems, (c) receipt of mental health services,
      (d) child's need for professional help, (e) suicidal behavior, and (f) police
      contacts. Total problem scores in the deviant range on the CBCL or TRF were
      significantly associated with poor outcomes 6 years later. The combination of
      deviant scores on both the CBCL and TRF was a powerful predictor of poor outcomes
      with 56% of the girls, and 36% of the boys with total problem scores in the
      deviant range on both instruments maladjusted 6 years later. The CBCL syndromes
      Attention Problems and Delinquent Behavior, and the TRF syndromes Delinquent
      Behavior, Somatic Complaints, and Social Problems significantly predicted poor
      outcomes. Teachers' reports predicted poor outcomes equally well or even somewhat
      better than parents' reports. It is important to include teacher information in
      the diagnostic assessment of children.

PMID- 7822628
TI  - Tests of three hypotheses regarding the predictors of delinquency.
AB  - Three hypotheses regarding the predictors of criminal activity in children and
      adolescents were assessed. These dealt with family, peer, and attitudinal
      variables, and they were explored in relation to indices based on seriousness of
      criminal activity and reoffending. The data were based on a sample of 338 youths
      who had been convicted of crimes and received probation or custody dispositions.
      The results provided general support for a model implicating family, peer, and
      attitudinal variables in youthful criminal activity. They did not, however,
      provide support for hypothesized interactions between family relationship and
      family structuring dimensions or between family relationship and peer association
      variables. The results did support an hypothesis regarding the independent
      contribution of an antisocial attitudes variable to the prediction of criminal
      activity.

PMID- 7822629
TI  - Methylphenidate influences on both early and late ERP waves of ADHD children in a
      continuous performance test.
AB  - Although it has frequently been reported that hyperactive children have
      abnormally small P3 amplitudes of the event-related potential (ERP), which are
      normalized by the stimulant drug methylphenidate (MPH), the literature is
      inconsistent concerning earlier ERP waves. The aim of the present study was to
      investigate whether the normalizing effect of a 10-mg dose of MPH was also
      apparent on earlier waves, such as the N1, the P2, and the N2, besides the P3.
      Twelve attention deficit with hyperactivity disorder (ADHD) children performed a
      Continuous Performance Test involving a button-press response to the letter X
      (CPT-X) under the influence of MPH in a double-blind placebo controlled acute
      dosage design. ERPs were recorded at Oz, Pz, Cz, and Fz. The expected increase of
      the parietal P3, both to targets and nontargets, was apparent, as well as a
      significant increase in percentage of hits. There also was a significant increase
      of an earlier, negative going, wave, the N2, with a frontal maximum, under the
      influence of MPH. This wave was probably a manifestation of an increase in
      processing negativity for target stimuli only, after the intake of the stimulant
      drug. No effect of MPH was found on the N1 or the P2.

PMID- 7822630
TI  - Observations and ratings of tics in school settings.
AB  - This paper describes the findings of a school-based tic assessment procedure
      (direct observations, teacher rating scales) for hyperactive children with
      comorbid tic disorder. Rates of motor tic frequency were found to be moderately
      stable across both days and school settings. Correlations between direct
      observations of tics and clinician rating scales were generally in the low to
      moderate range as were correlations between teacher and clinician rating scales.
      Overall rates of hyperactive/disruptive behaviors were not associated with rates
      of motor tic occurrence, and the behavioral symptoms of both disorders were also
      independent for specific intervals of time.

PMID- 7822631
TI  - A test of interpersonal theory of depression in children and adolescents using a
      projective technique.
AB  - Using a projective technique among child and adolescent psychiatric inpatients,
      we tested several hypotheses derived from Coyne's (1976b) interpersonal theory of
      depression. First, we predicted that depression would be associated with
      rejection, even controlling for the effects of aggression. Depression and
      rejection were associated only when aggression effects were covaried. Second, we
      hypothesized that the depression-rejection relation would display symptom
      specificity. Consistent with this hypothesis, we found that depression, but not
      anxiety, was related to rejection. Third, we assessed whether an index of
      interpersonal style--reliance on others--moderated the depression-rejection
      relation. Results suggested that depression and overreliance were both associated
      with high rejection scores, whereas the combination of low depression and low
      reliance on others was associated with low rejection scores. We found that
      results held across age groups. The implications of our findings for the
      interpersonal theory of depression in youngsters are discussed.

PMID- 7822633
TI  - Adolescent depressed mood and young adult functioning: a longitudinal study.
AB  - The present study examined two aspects of depressed mood in adolescence: (1)
      stability across the adolescent years and (2) ability to predict functioning in
      young adulthood. Participants included 82 Caucasian individuals (46 females and
      36 males) who were assessed one time per year for 4 consecutive years during
      adolescence (mean age at initial assessment = 13.5 years) and again during young
      adulthood (mean age = 19). The results indicated that depressed mood, as measured
      by the Children's Depression Inventory (CDI), remained relatively stable across
      at least 3 consecutive years of data collection during adolescence. In addition,
      adolescent CDI scores predicted young adult functioning in each of four areas:
      prosocial competence, self-esteem, externalizing problems, and internalizing
      problems.

PMID- 7822634
TI  - Intrabony lymphoma simulating periradicular inflammatory disease.
AB  - Intrabony lymphoma can mimic periradicular inflammatory disease of pulpal origin.
      Mismanagement of such cases can result if the clinician presumes the condition is
      inflammatory and fails to submit a tissue specimen for evaluation. This article
      reviews the features of jaw lymphoma and documents the importance of early
      diagnosis and histopathologic examination.

PMID- 7822632
TI  - Peer ratings of depression, anxiety, and aggression in inpatient and elementary
      school children: rating biases and influence of rater's self-reported depression,
      anxiety, and aggression.
AB  - Using parallel self-, peer, and teacher rating scales, several rating biases in
      children's peer ratings of depression, anxiety, and aggression were examined.
      Participants were 66 inpatient and 133 elementary school children (N = 199, 109
      boys, 90 girls; 61% white, 39% black) aged 8 to 12, and their teachers. Results
      showed significant halo bias in both the children's peer ratings and the
      teachers' ratings. Children's self-reports on each of the three traits were
      significantly related to their peer ratings of the same trait, while adjusting
      for socioeconomic status and the peers' teachers' ratings of the same trait.
      Children who rated themselves as high on each trait rated their peers
      significantly higher on the same trait than children who rated themselves as
      medium or low; and for depression and anxiety, those who rated themselves as
      medium rated their peers significantly higher on those traits than those who
      rated themselves as low. For both depression and aggression, children's self
      reports on the trait were significantly related to their peer ratings of the same
      trait, but not significantly related to their peer ratings of different traits.
      Disagreements between children's and teachers' ratings of the peers on all three
      traits were significantly related to child self-reports on each trait, indicating
      a possible distortion in children's peer ratings due to self-report. The
      implications of the results for both peer and others' assessments are discussed,
      and further investigation of rating biases in other informants' assessments is
      encouraged.

PMID- 7822636
TI  - A needed remarriage: dentistry and dental technology.

PMID- 7822635
TI  - Using the existing prosthesis as a provisional restoration.
AB  - The remaking of a fixed prosthesis provides a unique opportunity of converting
      the existing prosthesis to a provisional restoration for use while a replacement
      is being made. This article describes a technique for using existing prostheses
      that offers several advantages: less potential wear, increased provisional
      strength and retention, decreased clinical time and esthetically acceptable
      contours.

PMID- 7822637
TI  - For members only.

PMID- 7822638
TI  - Generalists and specialists.

PMID- 7822639
TI  - Perspectives on TMD.

PMID- 7822640
TI  - CDC issues TB guidelines.

PMID- 7822641
TI  - Porous bone mineral grafts boost long-term implant success.

PMID- 7822642
TI  - AIDS/HIV information hotline available.

PMID- 7822643
TI  - Researchers probe biochemistry of TMD.

PMID- 7822644
TI  - U.S. adult knowledge of risk factors and signs of oral cancers: 1990.
AB  - A sample of U.S. adults were asked questions to assess their knowledge of oral
      cancer as part of the 1990 Health Promotion and Disease Prevention Supplement of
      the National Health Interview Survey. Tobacco use was the only risk factor most
      adults identified correctly. Only 25 percent of those surveyed could identify one
      sign of oral cancer. Overall, there is extensive misinformation and a general
      lack of knowledge.

PMID- 7822645
TI  - Co-carcinogenesis and field cancerization: oral lesions offer first signs.
AB  - This article describes two cases of multifocal synchronous cell squamous cell
      carcinoma in high-risk patients. The initial presentation in both instances was
      an erythroplakic oral lesion. The importance of the team approach between the
      dentist and the oncologist for quality patient care is underscored.

PMID- 7822646
TI  - Assessing physicians' and dentists' oral cancer knowledge, opinions and
      practices.
AB  - Oral cancer is responsible for more than 8,000 deaths each year. This mortality
      may be attributed to lack of effective oral examinations by dental and medical
      primary care clinicians. This pilot project assessed the knowledge, opinions and
      practices of a group of Maryland physicians and dentists in oral cancer
      prevention, diagnosis and detection. Dentists performed more oral cancer
      examinations, although physicians saw more high-risk patients.

PMID- 7822647
TI  - A review of oral fungal infections and appropriate therapy.
AB  - Dental health care providers must recognize oral fungal pathogens that often are
      markers for early signs of immune deterioration. After accurate identification,
      appropriate therapy can be initiated. Predisposing factors for development of
      oral fungal infections, identification of oral fungal infections, treatment
      options and their relative costs are reviewed.

PMID- 7822648
TI  - Direct immunofluorescence vs. culture for detecting HSV in oral ulcers: a
      comparison.
AB  - Diagnostic tests may be necessary to determine the cause of oral ulcers. Direct
      immunofluorescence staining of oral smears supplies results much more quickly
      than viral culture, the "gold standard" for diagnosing HSV lesions. This study
      compares the sensitivity and specificity of direct immunofluorescence staining
      vs. viral culture and evaluates the usefulness of the two techniques for the
      general dental practitioner.

PMID- 7822649
TI  - The efficacy of an intraosseous injection system of delivering local anesthetic.
AB  - This article describes the clinical testing of a new system for the intraosseous
      delivery of local anesthesia. The author concluded that the system delivered
      local anesthetic very effectively (in some situations more effectively than the
      traditional delivery method), thus offering a great potential advantage to both
      dentists and patients.

PMID- 7822650
TI  - Assessing viral retention and elimination in rotary dental instruments.
AB  - The authors of this article used a laboratory model of herpes simplex virus
      infection to assess the potential for contamination of dental handpieces by a
      human viral pathogen. They found that although all the handpieces in the study
      were fitted with anti-retraction valves, it was not until the units were flushed
      internally and disinfected externally that the pathogens were eliminated.

PMID- 7822651
TI  - Occlusal trauma: a case in perspective.
AB  - The decision to initiate occlusal therapy as part of periodontal treatment is
      often controversial. This case report illustrates an indication for providing
      such therapy and suggests an appropriate sequence to follow for achieving a
      desirable outcome.

PMID- 7822652
TI  - Netherton's syndrome: a syndrome of elevated IgE and characteristic skin and hair
      findings.
AB  - Netherton's syndrome is a rare symptom complex characterized by greatly elevated
      IgE levels with atopic manifestations, an ichthyotic skin disorder (ichthyosis
      linearis circumflexa and/or congenital lamellar ichthyosis), and the
      characteristic hair abnormality trichorrhexis invaginata. It may be confused with
      atopic dermatitis but does not respond to topical corticosteroid treatment.
      Netherton's syndrome is therefore of considerable importance to allergists. In
      this article we report the results of the clinical and immunologic evaluation of
      a previously unreported patient who responded to treatment with 12% ammonium
      lactate lotion and management of his allergic disease. Furthermore, we have
      reviewed the English literature and compared the findings in our patient with
      those of 43 other reported patients. Our patient shared the features of other
      previously reported patients with this disorder. We conclude that this disease
      should be included among the other disorders with elevated IgE. Patients may
      benefit from evaluation and treatment of their allergic symptoms and topical skin
      treatment with ammonium lactate.

PMID- 7822653
TI  - Acquired deficiency in C1-inhibitor associated with signet ring cell gastric
      adenocarcinoma: a probable connection of antitumor-associated antibodies,
      hemolytic anemia, and complement turnover.
AB  - BACKGROUND: Acquired deficiency in C1-inhibitor (C1-INH) associated with
      malignancy is often asymptomatic because clinical manifestations are not
      dependent on a critical complement threshold (in contrast to hereditary C1-INH
      deficiency). Increased complement consumption involving different kinds of
      antibodies is the postulated mechanism for this disease, but other factors must
      play an important role. CASE REPORT: A 76-year-old woman with unremarkable
      medical history experienced three episodes of angioedema over 6 months.
      Investigations revealed a complement profile characteristic of acquired
      deficiency in C1-INH, a hemolytic anemia, and a signet ring cell adenocarcinoma
      (linitis plastica). A gastrectomy and a splenectomy were performed. The
      postoperative course was characterized by a complete disappearance of the
      symptoms of angioedema and hemolytic anemia. A local recurrence of the tumor 5
      months later could not be resected. The patient died 17 months after the initial
      surgery was performed. RESULTS: Quantitative and functional analyses of the
      complement factors showed persistent excessive complement consumption. Markers of
      hemolytic anemia disappeared after tumor removal but recurred in the second part
      of the disease evolution. Immunohistochemical findings in tumor tissue showed
      loss of normal blood group antigens but expression of Lea antigen, as well as C1q
      deposition. CONCLUSION: To explain the whole clinical and laboratory picture, we
      hypothesize a connection between tumor immunohistochemical profile, complement
      consumption, and hemolytic anemia. Tumor cell surface antigens might lead to a
      permanent but asymptomatic complement consumption that is worsened and becomes
      clinically manifest by superimposed hemolytic anemia caused by cross-reactive
      antibodies to newly expressed blood group antigens on tumor cells. This
      hypothesis should be confirmed by other observations.

PMID- 7822654
TI  - alpha-Amylase contained in bread can induce food allergy.

PMID- 7822655
TI  - The effects of nebulized recombinant interferon-gamma in asthmatic airways.

PMID- 7822656
TI  - Immediate, late, and delayed skin test responses to Centruroides vittatus
      scorpion venom.

PMID- 7822657
TI  - Anaphylaxis to Laminaria.

PMID- 7822658
TI  - Latex: a potential hidden "food" allergen in fast food restaurants.

PMID- 7822659
TI  - Oral versus repository corticosteroid therapy after hospitalization for treatment
      of asthma.
AB  - Tapering regimens of oral steroids may be difficult or confusing for some
      patients. Repository steroids have been shown to be as effective as tapering oral
      doses in preventing relapse after emergency treatment. This study was undertaken
      to determine whether repository steroids are as effective as tapering oral
      steroids in preventing relapse after hospitalization for treatment of asthma.
      Twenty-six patients with acute exacerbations of asthma requiring treatment for 24
      to 72 hours with parenteral steroids were randomized into two groups. Both groups
      received oral prednisone, 60 mg daily, when parenteral steroids were
      discontinued. At discharge, one group received intramuscular placebo and oral
      prednisone tapered over 8 days, and the other received 80 mg intramuscular
      methylprednisolone sodium acetate and oral placebo. At discharge and 2-week
      follow-up, patients were interviewed and examined, and spirometry results were
      obtained. There was little difference between groups in ratings of symptoms at
      discharge or follow-up. Both groups had less wheezing at follow-up than at
      discharge, though the improvement was significant only in the repository steroid
      group (p < 0.05). Mean forced expiratory volume in 1 second, forced vital
      capacity, peak expiratory flow rate improved at follow-up in both groups. No
      significant differences in outcome were found between the oral and repository
      steroid groups.

PMID- 7822660
TI  - Evaluation of serum eosinophilic cationic protein as a marker of disease activity
      in chronic asthma.
AB  - BACKGROUND: Serum eosinophil cationic protein (ECP) has been promoted as a direct
      marker of eosinophilic inflammation of the bronchi, especially helpful in
      patients with asymptomatic asthma. OBJECTIVE: To evaluate serum ECP against
      indirect clinical markers of disease activity, we compared symptom score,
      bronchial obstruction, bronchial responsiveness, and blood eosinophil counts with
      serum ECP levels in children with symptomatic and asymptomatic chronic asthma and
      assessed ECP in others with allergic rhinitis alone. METHODS: Twenty-four
      children with symptomatic asthma, 10 children with asymptomatic asthma, and 16
      children with allergic rhinitis were studied. Measurements were made by
      standardized symptom questionnaire, spirometry, inhalation challenge with
      histamine or methacholine, blood eosinophil counts, and radioimmunoassay of serum
      ECP. RESULTS: There was no difference in serum ECP levels between the symptomatic
      asthma, asymptomatic asthma, or rhinitis groups, and most values were within the
      normal range. Activated eosinophil counts were higher in subjects with
      symptomatic asthma than in those with asymptomatic asthma but not in subjects
      with rhinitis. Serum ECP correlated with eosinophil counts (p < 0.01) but not
      symptom score, forced expiratory volume in 1 second (FEV1), forced expiratory
      flow, mid-expiratory phase (FEF25-75), or provocative concentration causing a 20%
      fall in FEV1 (PC20). Symptom scores correlated with PC20 (p < 0.005) and FEF25-75
      (p < 0.01). CONCLUSION: Serum ECP is a poor indicator of disease activity in
      chronic asthma and cannot differentiate bronchial from nasal inflammation.

PMID- 7822661
TI  - Budesonide treatment of moderate and severe asthma in children: a dose-response
      study.
AB  - OBJECTIVE: The purpose of the study was to evaluate the dose-response
      relationships of the inhaled corticosteroid budesonide in a double blind
      crossover study in 19 children with moderate and severe asthma. METHODS: A 2-week
      placebo treatment period (run-in) was followed by three 4-week treatment periods
      during which 100, 200, and 400 micrograms of budesonide were given per day in
      randomized order. Urinary cortisol excretion, lung functions, and protection
      against exercise-induced asthma were assessed at the end of run-in and each
      treatment period. Furthermore, morning and evening peak expiratory flow rates,
      day and night symptoms, and use of rescue beta 2-agonists were recorded
      throughout the study. RESULTS: One hundred micrograms of budesonide per day
      markedly improved symptoms, morning and evening peak expiratory flow rates, and
      use of rescue beta 2-agonists (p < 0.01). No further improvement was seen in
      these parameters with increasing doses of budesonide. In contrast, a significant
      dose-response effect was found on lung functions measured at the hospital and
      fall in lung functions after exercise (p < 0.001); 200 micrograms was
      significantly better than 100 micrograms, and 400 micrograms was significantly
      better than 200 micrograms. About 53% of the maximum effect against exercise
      induced asthma was achieved by the lowest budesonide dose (p < 0.001), and about
      83% by the highest dose. No significant differences were seen in urinary cortisol
      excretion between run-in and the various budesonide doses. CONCLUSIONS: Low doses
      of budesonide, which are not associated with any systemic side effects, have a
      marked antiasthma effect in children. Protection against exercise-induced asthma
      requires higher doses than achievement of symptom control.

PMID- 7822662
TI  - Self-management teaching programs and morbidity of pediatric asthma: a meta
      analysis.
AB  - BACKGROUND: Self-management teaching programs are becoming an important asset in
      the management of pediatric asthma. OBJECTIVE: The study was designed to evaluate
      the impact of self-management teaching programs on the morbidity of pediatric
      asthma. METHODS: The meta-analysis included randomized clinical trials, published
      between 1970 and 1991, addressing the outcome of morbidity. Studies were
      retrieved from searches of MEDLINE, American Journal of Nursing International
      Index, and Dissertation Abstracts Online Database. The quality of studies was
      assessed with the scale of Chalmers. The pooled effect size was calculated by the
      method of Hedges. RESULTS: The literature search retrieved 23 randomized clinical
      trials, but 12 studies had to be excluded. Global score of quality of studies
      (Chalmers' scale) was fair, 51.6% +/- 9.9%. As indicated by the effect size (ES)
      of the pooled studies, self-management teaching did not reduce school absenteeism
      (ES: 0.04 +/- 0.08), asthma attacks (ES: 0.09 +/- 0.14), hospitalizations (ES:
      0.06 +/- 0.08), hospital days (ES: -0.11 +/- 0.08), or emergency visits (0.14 +/-
      0.09). CONCLUSION: Self-management teaching programs do not seem to reduce
      morbidity, and future programs should focus more on intermediate outcomes such as
      behavior.

PMID- 7822663
TI  - The effect of MK-0591, a novel 5-lipoxygenase activating protein inhibitor, on
      leukotriene biosynthesis and allergen-induced airway responses in asthmatic
      subjects in vivo.
AB  - BACKGROUND: The 5-lipoxygenase metabolites of arachidonic acid are likely to be
      involved in the pathophysiology of atopic asthma. We investigated the effect of
      pretreatment with MK-0591, a novel 5-lipoxygenase activating protein inhibitor,
      on allergen-induced early asthmatic reactions (EARs) and late asthmatic reactions
      (LARs), and subsequent airway hyperresponsiveness to histamine. METHODS: Eight
      atopic men with mild to moderate asthma aged 19 to 31 years, (forced expiratory
      volume in 1 second [FEV1] > or = 67% of predicted value, histamine provocative
      concentration causing a 20% fall in FEV1 [PC20] < 4 mg/ml) and documented EAR and
      LAR to house dust mite extract participated in a two-period, double-blind,
      placebo-controlled, crossover study. During each study period histamine PC20 was
      measured 2 days before and 1 day after a standardized allergen inhalation
      challenge test. MK-0591 was administered in 3 oral doses of 250 mg each at 24,
      12, and 1.5 hours before inhalation of allergen. Biochemical activity of MK-0591
      was determined by calcium ionophore A-23187-stimulated leukotriene (LT)B4
      biosynthesis in whole blood ex vivo and by urinary LTE4 excretion. Airway
      response to allergen was measured by FEV1 (percent fall from baseline). The EAR
      (0 to 3 hours) and the LAR (3 to 8 hours) were expressed as corresponding areas
      under the time-response curves. RESULTS: MK-0591 and placebo did not differ in
      their effects on prechallenge FEV1 (p = 0.10). As compared with the value before
      pretreatment, MK-0591 blocked LTB4 biosynthesis and LTE4 excretion by a mean of
      98% (range, 96% to 99%; p < 0.002) and 87% (range, 84% to 96%; p < 0.046),
      respectively, from 0 to 24 hours after allergen challenge. Both the EAR and the
      LAR were significantly reduced after administration of MK-0591 as compared with
      placebo, with a mean inhibition of 79% (p = 0.011) and 39% (p = 0.040),
      respectively. Allergen-induced airway hyperresponsiveness was not significantly
      different between the two pretreatment periods (p = 0.37). CONCLUSIONS: In this
      study oral MK-0591 prevented leukotriene biosynthesis after allergen challenge in
      patients with mild to moderate asthma. The results of our study indicate that 5
      lipoxygenase products play an important role during the EAR, whereas their
      contribution to the pathophysiology of the LAR seems to be of less importance.

PMID- 7822664
TI  - Extrathoracic and intrathoracic airway responsiveness in sinusitis.
AB  - BACKGROUND: Asthma associated with sinusitis is supposed to be sustained by
      bronchoconstrictive reflexes originating in extrathoracic airway (EA) receptors.
      OBJECTIVE: The study was designed to evaluate the relationship between EA
      responsiveness and bronchial responsiveness in sinusitis. METHODS: We performed
      histamine inhalation challenge in 106 patients with chronic sinusitis, during
      disease exacerbation and after treatment with antimicrobials and nasal
      flunisolide (100 micrograms daily) for 2 weeks. Forced expiratory volume in 1
      second (FEV1) and maximal mid-inspiratory flow (MIF50) were the respective
      indexes of bronchial and EA narrowing; the histamine concentrations causing a 20%
      fall in FEV1 (PC20) and 25% drop in MIF50 (PC25MIF50) were used as thresholds of
      bronchial and EA responsiveness. Thresholds of 8 mg/ml or less were assumed to
      indicate bronchial hyperresponsiveness (B-HR) or EA hyperresponsiveness (EA-HR).
      RESULTS: During sinusitis exacerbation 76 patients had EA-HR, which in 46 was
      associated with B-HR. The values of PC20 were closely related with those of
      PC25MIF50 (p < 0.001). EA-HR and B-HR were strongly associated with pharyngitis.
      After treatment, mean PC25MIF50 and PC20 were significantly increased (p <
      0.001). The improvement of PC25MIF50 was closely related to that of PC20 (p <
      0.001) and to the decrease in neutrophils in nasal lavage (p < 0.05). EA-HR
      reversed in 58 patients and improved in 10; B-HR reversed in 29 and improved in
      12. CONCLUSIONS: Our findings suggest that in sinusitis, B-HR may be sustained by
      constrictive reflexes originating in pharyngeal receptors, made hypersensitive by
      seeding of the inflammatory process.

PMID- 7822665
TI  - Protein content in bronchoalveolar lavage fluid of patients with asthma and
      control subjects.
AB  - BACKGROUND: Secretory component (SC), Clara cell protein (CC10) and to some
      extent, IgM are proteins locally synthetized in airways. Albumin, alpha 2
      macroglobulin and alpha 1-antitrypsin are mainly plasma proteins. In patients
      with asthma, blood proteins may occur in greater amounts in bronchoalveolar
      lavage fluid (BALF) than in control subjects because of plasma extravasation.
      These proteins were measured in BALF to define markers of local synthesis and
      plasma exudation. METHODS: Twenty-four patients with asthma (mean age, 40 +/- 3.1
      years) and 24 control subjects (mean age, 29 +/- 11 years) were tested. Five
      aliquots of saline solution (50 ml) were instilled, and the recovered BALF was
      stored. Clara cell protein was measured by a sensitive immunoassay technique
      based on the agglutination of latex particles. SC, immunoglobulins, alpha 2
      macroglobulin, alpha 1-antitrypsin, and albumin were measured by an
      immunoradiometric assay. Protein concentrations were normalized to albumin.
      RESULTS: In BALF from patients with asthma there was a significant increase in
      alpha 2-macroglobulin and IgM and a significant decrease of SC, alpha 1
      antitrypsin, and Clara cell protein compared with control subjects. Also, the
      ratio to albumin was significantly increased for alpha 2-macroglobulin and IgM
      and decreased for SC. There was no correlation between the severity of asthma and
      the amount of proteins. CONCLUSIONS: BALF protein content is significantly
      different in patients with asthma and control subjects, for proteins produced
      locally and derived from plasma.

PMID- 7822666
TI  - Establishment of human IgE system in severe combined immunodeficient mice with
      peripheral blood mononuclear cells from asthmatic children.
AB  - The frequency of allergic diseases, such as asthma, has increased rapidly during
      the past decade; however, the exact mechanisms have not been established. In this
      study we tried to establish an in vivo system to investigate immune regulation of
      allergic diseases by using severe combined immunodeficient (SCID) mice.
      Peripheral blood mononuclear cells isolated from asthmatic children or normal
      adults were injected into peritoneal cavities of SCID mice. Human IgG, IgA, IgM,
      and IgE could be detected in SCID mice reconstituted with human PBMCs (SCID-PBL
      hu mice) 3 weeks later. Moreover, the mice injected with peripheral blood
      mononuclear cells from asthmatic children had much higher IgE levels than mice
      reconstituted with cells from normal adults. Phenotypic analysis of spleen cells
      and peritoneal exudate cells from SCID-PBL-hu mice demonstrated that human
      lymphocytes could survive in the peritoneal cavity and spleen for several months.
      After intraperitoneal immunization, mite-specific IgE antibodies could also be
      detected in SCID-PBL-hu mice. This study indicates that the human IgE system can
      be established in SCID mice and that this model can be used to study the
      regulation of IgE production and the immunopathogenesis of human allergic
      disease.

PMID- 7822667
TI  - A reduction in allergen-induced Fc epsilon R2/CD23 expression on peripheral B
      cells correlates with successful hyposensitization in grass pollinosis.
AB  - BACKGROUND: The cellular basis for the mechanism of specific hyposensitization is
      still unclear. OBJECTIVE: We prospectively studied the effect of immunotherapy on
      allergen-induced proliferation and Fc epsilon R2/CD23 expression of lymphocytes.
      METHODS: Mononuclear cells prepared from the peripheral blood of 22 patients with
      grass pollen (GP) allergy before, during, and after a preseasonal immunotherapy
      period with GP were stimulated with GP or control antigens. Tritiated thymidine
      uptake and percentage of CD23+ B cells were determined daily during days 6 to 8
      and compared with lymphocyte responsiveness of 11 only symptomatically treated
      atopic patients and 14 nonatopic individuals. RESULTS: GP-induced lymphocyte
      proliferative response of both hyposensitized and symptomatically treated GP
      allergic patients decreased markedly before the pollen season and rose again
      after seasonal allergen exposure, whereas a long-lived decrease in GP-induced Fc
      epsilon R2/CD23+ B cells was only observed in GP-treated patients. Alterations in
      Fc epsilon R2/CD23 expression were closely related to changes in symptoms and
      medication requirement during the following pollen season. In contrast,
      immunotherapy had no effect on Fc epsilon R2/CD23 expression of B cells without
      stimulation or on B cells cultured in the presence of control antigens.
      CONCLUSION: Because Fc epsilon R2/CD23 expression on B cells is antagonistically
      regulated by the cytokines interleukin-4 and interferon-gamma, the decrease of
      allergen-induced Fc epsilon R2/CD23+ B cells indicates an altered cytokine
      secretion pattern of the allergen-specific T lymphocytes with a predominance of
      interferon-gamma.

PMID- 7822668
TI  - Immunotherapy: a one-year prospective study to evaluate risk factors of systemic
      reactions.
AB  - BACKGROUND: We did a prospective study in Atlanta, Georgia, during 1991 on the
      rate of systemic reactions caused by immunotherapy in a clinic that uses aqueous
      allergen extracts. METHODS: Immunotherapy reactions were monitored. Symptoms were
      recorded with respect to time of onset, involvement of respiratory tract or skin,
      and presence of hypotension. RESULTS: There were 98 systemic reactions in 96
      patients (1 per 1600 visits or 1 per 47 patients). There was no direct
      relationship to seasonal pollen counts. There was, however, a correlation with
      the August to October increase in mold counts. There was no correlation between
      reactions and the age of the patient or the age of the extract. Patients were
      more likely to experience a reaction during the buildup phase than during
      maintenance therapy. The time of onset and the severity of the reaction were in
      agreement with previous reports. Severe reactions that included hypotension all
      occurred less than 30 minutes after the injection. In contrast to previous
      reports, patients with asthma were not at higher risk for a systemic reaction.
      CONCLUSION: Immunotherapy has a significant but low rate of systemic reaction.
      Potentially serious reactions may be mitigated by taking extra precautions during
      the earlier phases of an immunotherapy program and during seasons when mold
      counts are high.

PMID- 7822669
TI  - Latex allergen in respirable particulate air pollution.
AB  - OBJECTIVE: Urban air samples contain numerous irregular respirable black
      particles, which may be airborne tire fragments. A major component of tires is
      natural latex. Proteins of natural latex can act as adjuvants and as antigens
      capable of eliciting immediate hypersensitivity, making their presence in
      particulate air pollution an important clinical issue. METHODS: Particulate air
      pollutants were collected by volumetric sampling devices and characterized by
      optical microscopy, chemical solubility tests, and mass spectrometry. Extracts of
      rubber tire fragments were tested for elutable latex antigens by antibody
      inhibition assays. RESULTS: Identification of latex in air samples and milled
      material from automobile tires was supported by mass spectrometry results and was
      further confirmed by physical appearance and chemical solubility studies.
      Competitive immunoassay confirmed the presence of extractable latex antigens from
      rubber tire fragments. CONCLUSIONS: Latex antigens are extractable from rubber
      tire fragments, which are abundant in urban air samples. Given the adjuvant and
      sensitizing effects of latex, these airborne particles could contribute, through
      direct and indirect mechanisms, to the increase in both latex sensitization and
      asthma. The impact of these particles should be considered in the issue of
      morbidity and mortality rates associated with respiratory diseases and air
      pollution.

PMID- 7822670
TI  - Localization of histamine N-methyltransferase messenger RNA in human nasal
      mucosa.
AB  - BACKGROUND: Histamine is metabolized mainly by histamine N-methyltransferase
      (HMT) to N tau-methylhistamine in human nasal mucosa. Human HMT cDNA has been
      cloned and expressed in COS cells. The purpose of this study was to determine the
      localization of HMT METHODS: The fragment (nucleotide residues 430-1055) of human
      HMT cDNA was subcloned in a Bluescript vector (Stratagene, La Jolla, Calif.), and
      HMT sense anti-sense RNA probes were made with T7 and T3 RNA polymerases. In situ
      hybridization with digoxigenin-labeled RNA probes was performed on surgical
      specimens of human nasal turbinates. RESULTS: HMT mRNA was localized in cells in
      the epithelium and submucosa, and densely in endothelial cells of vessels. No HMT
      mRNA was identified in the submucosal glands. The presence of HMT mRNA was
      confirmed by Northern blot analysis, and HMT activities were also detected in
      nasal mucosa. CONCLUSION: Our study indicates that endothelium expresses HMT
      mRNA, whereas cells in the epithelium and submucosa, which remain unidentified,
      are an additional source of HMT mRNA.

PMID- 7822671
TI  - 51st Annual Meeting of the American Academy of Allergy and Immunology. New York
      City, New York, February 24-March 1, 1995. Abstracts.

PMID- 7822672
TI  - Disposable lenses and the marginal dry eye patient.
AB  - BACKGROUND: The patient with marginal dry eye can experience difficulty wearing
      soft contact lenses. Various lens types have been prescribed for the marginal dry
      eye patient. The introduction of disposable soft lenses adds another lens type
      that may be useful for this patient population. METHODS: This double-blind pilot
      study involved 10 subjects. The marginal dry eye subjects were fit with thin
      (0.07 mm at -3.00) and standard (0.105mm at -3.00 thickness), high water content
      (58 percent) disposable soft contact lenses. The lens type was alternated on a
      weekly basis for 3 weeks. Patient preference regarding acuity, comfort, and
      overall impression was determined. Corneal response was also evaluated. RESULTS:
      If there was a preference, the marginal dry eye subjects preferred the thinner
      lens, which also produced the least adverse corneal response. The average daily
      wearing time was 9 hours, and lens lubricants were used an average of three times
      per wearing period. CONCLUSIONS: This pilot study indicates that high water
      content, disposable soft lenses used on a daily wear basis can be worn by the
      marginal dry eye patient. Although individual variation exists, the thinner lens
      design was more readily accepted.

PMID- 7822673
TI  - The effects of gender and birth control pill use on spontaneous blink rates.
AB  - BACKGROUND: Two major reference works suggest that men and women blink
      spontaneously at different rates, but they disagree with regard to which gender
      blinks faster. METHODS: Spontaneous blink rates of 59 males and 86 females, 44 of
      whom were taking birth control (BC) pills, were measured for 5 consecutive
      minutes. Schirmer test results and tear break-up times (TBUTs) were also
      obtained. RESULTS: Females taking BC pills blinked at a mean rate of 19.6 times
      per minute, females not taking birth control pills blinked 14.9 times per minute,
      and males blinked 14.5 times per minute. There were very large differences
      between blink rates for individuals in each of the groups. No strong associations
      were found between spontaneous blink rates and a history of contact lens use,
      tear break-up time, Schirmer test results, temperature or humidity in the
      examination room, subject age, or menstrual cycle phase. CONCLUSIONS: The 32
      percent increase in mean blink rate for females taking BC pills suggests that the
      pills affect at least one of the mechanisms that control spontaneous blinking,
      but it is unclear how they accomplish this.

PMID- 7822674
TI  - Patient-induced power changes in rigid gas permeable contact lenses: a case
      report and literature review.
AB  - BACKGROUND: The tendency for rigid gas permeable contact lenses to suffer
      parameter changes is well known. The following case report identifies an
      infrequently reported instance of marked power change associated with
      inappropriate abrasive cleaning. METHODS: A patient presented to our clinic with
      contact lens-related decrease in vision that was determined to have been the
      result of a patient-induced lens power change. A review of the literature
      uncovered similar reported cases. Further evaluation revealed the existence of
      common etiological factors. RESULTS: Consideration of elements common to this
      particular case and the available literature allows for the construction of a
      profile of a patient at risk for this lens complication. These include prior
      history of PMMA wear, use of an abrasive cleaner, silicone-acrylate lenses, and
      digital cleaning. CONCLUSIONS: Contact lens patients may present with complaints
      of decreased vision that are secondary to a number of different causes. One
      potential problem identified in this report is that of lens power change induced
      by inappropriate patient cleaning. It is hoped that this will serve to alert
      other practitioners to patients who correspond to this profile.

PMID- 7822675
TI  - Multisite comparison of contact lens modalities. Daily disposable wear vs.
      conventional daily wear in successful contact lens wearers.
AB  - BACKGROUND: RESULTS are reported for the first year of one facet of an ongoing
      multisite clinical investigation. In this article, one subpopulations of subjects
      wearing soft contact lenses on a daily disposable wear schedule (DDW is compared
      to a second subpopulation wearing lenses on a conventional daily wear (CDW)
      basis. METHODS: All subjects recruited were successfully wearing lenses on a
      conventional daily wear basis at the time of enrollment. In addition to an
      initial visit, follow-up visits occurred at 1, 4, 12, 26 and 52 weeks. Areas of
      assessment included vision, comfort, ocular health, subject-reported symptoms,
      lens surface deposits and overall satisfaction. A total of 70 subjects were
      dispensed lenses on a daily disposable schedule and 125 subjects were dispensed
      lenses on a conventional daily wear schedule. RESULTS: Five DDW subjects and 15
      CDW subjects discontinued before the 52-week follow-up visit. When the findings
      of the 52-week follow-up visit were compared, the DDW group performed
      significantly better than the CDW group in the following areas: Snellen visual
      acuity, subjective vision and comfort assessment, symptomatology, lens deposits
      and overall satisfaction. In addition, while performance levels tended to improve
      in the DDW group when the results from the 52-week follow-up visit were compared
      with the 1-week follow-up visit, they tended to decline in the CDW group over
      this period of time. Subjects wearing lenses on a daily disposable basis were
      significantly less likely to report for an unscheduled visit than subjects
      wearing lenses on a conventional wear basis, with the DDW subjects reporting with
      less serious ocular health problems. CONCLUSIONS: Patients who were wearing
      conventional reusable daily wear lenses and refit into lens wear on a daily
      disposable basis realized clinically significant advantages compared to a similar
      population of patients who were refit with lenses worn on a conventional daily
      wear basis.

PMID- 7822676
TI  - Spectacles and custom toric hydrogel contact lenses: a comparison of vision.
AB  - BACKGROUND: The quality of vision obtained through spectacles and toric hydrogel
      contact lenses is important when determining which correction type is best.
      METHODS: Twenty-six subjects with 0.75D-3.50D of refractive astigmatism were
      selected to wear Sunsoft Custom toric hydrogel contact lenses. Snellen acuity and
      contrast sensitivity measurements were gathered with both toric hydrogel lenses
      and spectacles. At the conclusion of the study each subject completed a
      questionnaire rating his or her preference for spectacles or toric hydrogel
      lenses based on the quality of vision with each. RESULTS: Our findings reveal no
      statistically significant difference when comparing contrast sensitivity
      thresholds, Snellen acuity thresholds or subjective preference between spectacles
      and toric hydrogel lenses. CONCLUSIONS: Based on quality of vision, practitioners
      should not hesitate to recommend toric hydrogel lenses in addition to the
      traditional spectacle correction as a viable method of correction for the
      moderately astigmatic patient.

PMID- 7822677
TI  - Effects of long term extended wear of PMMA lenses on corneal function: a case
      report.
AB  - BACKGROUND: Recent studies have shown that some long-term PMMA contact lens
      wearers who are presumably exposed to hypoxia can develop modest but permanent
      changes in corneal structure and function. What is not known is the corneal
      effects that may result from severe and long-term exposure to an hypoxic
      environment. This case report is presented to illustrate an extreme example of
      the effects of the cornea from prolonged exposure to hypoxia. METHODS: A 37-year
      old male who had worn PMMA lenses on a 2-week extended wear basis for 20 years
      was examined in the laboratory to assess changes in corneal structure and
      function. Function was determined by monitoring the rate at which the cornea
      recovered from induced edema and is expressed as a percent recovery per hour
      (PRPH). Morphology was studied via specular microscopy. RESULTS: For this
      subject, the PRPH was 39.6 percent/hr and 40.5 percent/hr for right and left eyes
      respectively; these values are substantially reduced compared to the reported
      55.3 percent/hr for an age-matched, non-contact lens wearing population. Specular
      microscopy demonstrated reduced cell counts of 1,052 cells/mm2 OD and 1,741
      cells/mm2 OS compared to an age adjusted normal population with 2,853 +/- 320
      cells/mm2. CONCLUSIONS: This case example appears to represent an extreme case of
      contact lens abuse and the effects of long-term hypoxic contact lens wear on
      corneal function.

PMID- 7822678
TI  - The effects of daily wear contact lenses on goblet cell density.
AB  - BACKGROUND: Some patients can wear contact lenses with a low tear breakup time
      while others with an identical tear breakup time cannot wear lenses. This
      suggests the current method of tear film assessment is inadequate at
      differentiating between these two types of patients. The study attempts to expand
      our knowledge of the tear film with special attention directed to a critical yet
      little studied component: mucin. Mucin is vital to maintenance of the tear film
      and functions as a tear film stabilizer. The condition of the precorneal tear
      film is a major determinant in the success of contact lens wear. METHODS:
      Eighteen subjects free of ocular surface disease who had never worn contact
      lenses had the goblet cell density of their inferior bulbar conjunctiva
      determined by impression cytology. The subjects were then fit in a 38 percent
      water polymacon lens and their goblet cell density determined on a monthly basis
      for 6 months. RESULTS: Nearly a 2-fold increase in goblet cell density was
      observed in 88 percent of the subjects over the 6-month period. The first
      statistically significant increase occurred 5 months after the initiation of lens
      wear when the goblet cell density rose from 4.19-7.84 percent. CONCLUSIONS: We
      speculate the increase in goblet cells is an adaptive response of the ocular
      surface to a coated daily wear contact lens.

PMID- 7822679
TI  - Presbyopic drivers' vision through a convex rear view mirror.
AB  - BACKGROUND: Monovision is a commonly used modality for the presbyope who wants to
      wear contact lenses. If the add for near vision is in the left eye, driving an
      automobile creates a circumstance whereby the lens wearer cannot obtain a clear
      image in that eye of distant objects seen in the driver's side outside rear view
      mirror. METHODS: We have discovered that a stick-on convex mirror eliminates this
      problem by neutralizing either some or all of the power of the add. RESULTS: The
      driver wearing an add in the left eye can then obtain a clear image in that eye
      of objects behind and to the side of the automobile.

PMID- 7822680
TI  - Review of oximes available for treatment of nerve agent poisoning.
AB  - A review was conducted of papers describing the use of N-methyl-2
      pyridinealdoxime (PAM), toxogonin or HI-6 as antidotes to the nerve agents tabun,
      sarin, soman and VX. The review included use of the oxime alone, oxime plus
      atropine and oxime plus atropine plus diazepam, given therapeutically, i.e. after
      nerve agent, in all cases. Experiments with any of these compounds given
      prophylactically were not considered. The review also included protocols of
      pyridostigmine prophylaxis and oxime-atropine therapy (with or without diazepam).
      It was difficult to draw conclusions as to the best oxime to use, because of lack
      of data in many cases. The identity of the oxime did not appear to be important
      when pyridostigmine prophylaxis was combined with atropine-oxime-diazepam
      therapy; in these cases, very good protection was observed in guinea pigs against
      all four nerve agents. The choice of oxime based on the data presently available
      may well depend on factors other than protection against lethality, such as cost
      and availability of the oxime and human toxicity of the oxime. This last factor
      was also reviewed, and the results showed that toxogonin is likely to cause more
      side-effects than PAM or HI-6. The efficacy of the oximes against the emerging
      threat agent GF was also reviewed.

PMID- 7822681
TI  - Chromium-induced micronuclei in fish.
AB  - An investigation of the cytogenetic effects of chromium (Cr(VI) and Cr(III)) in
      Prussian carp (Carassius auratus gibelio) was made. For detecting cytogenetic
      damage, micronuclei induction in fish erythrocyte cells was employed. Fish were
      investigated 100 m above and 400 m below the discharge of leather waste products
      into the river Ljubljanica, and by exposing fish to three doses of chromium
      (Cr(VI) and Cr(III)) in the laboratory. The exposure of fish to various
      concentration levels (sub-lethal) of chromium under laboratory and field
      conditions caused an increase in the frequency of micronuclei compared with the
      control groups.

PMID- 7822682
TI  - Early hepatic changes induced by nuarimol in rats.
AB  - It is commonly believed that in short-term tests hepatic cytochrome P-450b
      inducers stimulate liver enlargement and mitogenesis in the absence of overt
      hepatotoxic effects. In this investigation male Wistar rats received naurimol (an
      organochlorine pesticide) in one, three and five oral doses of 31.5, 62.5 and 125
      mg kg-body wt. day-, whereupon the effects on liver were determined. The early
      effects were dose-dependent increases in p-nitroanisole metabolism, hepatocyte
      proliferation (DNA synthesis and mitotic activity) and liver weight. Five
      administrations of the lowest does (31.5 mg kg-1 body wt. day-1) did not change
      liver weight, despite increased p-nitroanisole metabolism and hepatocyte
      proliferation. In contrast to p-nitroanisole metabolism and hepatomegaly,
      proliferation was only transient and disappeared even when treatment continued.
      The increase in binuclear hepatocytes and signs of necrosis suggested that the
      hepatomitogenic effect of nuarimol reflected a regenerative response, which may
      simulate the proliferation caused by partial hepatectomy.

PMID- 7822683
TI  - Effects of lead loads on branchial osmoregulatory mechanisms in the rainbow trout
      Oncorhynchus mykiss.
AB  - Exposure of rainbow trout to lead chloride (PbCl2, 1 ppm) in fresh water killed
      all animals within 16 days. Exposure to this lethal dose for 6 days only showed a
      significant increase in the haematocrit. Calcium, sodium and chloride
      concentrations in plasma were not notably modified. Both the influx and the net
      flux of sodium fluctuated much less than the diffusional water fluxes through
      secondary lamellae in gills. Branchial Na,K-ATPase, Ca-ATPase and HCO3-ATPase
      activities were not sensitive to lead toxicity. Lead caused a cellular 'wave
      shaped' degeneration and renewal with modification in the number and morphology
      of chloride cells. Results are discussed in relation to the hydromineral balance
      of the trout.

PMID- 7822684
TI  - Effect of protein malnutrition on the neurobehavioural toxicity of styrene in
      young rats.
AB  - Neurotoxic effects of styrene on certain biochemical and behavioural indices were
      studied in young rats kept deficient in protein during the weaning period. Young
      rats fed a low-protein diet showed a significant decrease in the level of
      dopamine and an increase in frontocortical [3H]serotonin binding in comparison to
      the group of rats fed a normal protein diet. These rats also showed a significant
      increase in foot shock-induced aggressive behaviour, while no changes in
      amphetamine-induced locomotor activity, levels of norepinephrine and serotonin
      and binding of [3H]spiperone to striatal membrane were observed. On exposure to
      styrene, rats fed a normal protein diet showed a decrease in dopamine level and
      an increase in foot shock-induced aggressive behaviour only, with no significant
      change in other parameters, in comparison to the respective controls. It was,
      however, interesting to note that when rats fed a low-protein diet were exposed
      to styrene they showed a significant decrease in the levels of norepinephrine,
      dopamine and serotonin and an increase in the binding of [3H]spiperone and [3H]5
      HT to striatal and frontocortical membranes, respectively. A significant increase
      in foot shock-induced aggressive behaviour and amphetamine-induced locomotor
      activity was also observed in this group of animals in comparison to those fed a
      low-protein diet. The biochemical and behavioural data indicate that protein
      deficiency makes young animals more vulnerable and it is an important
      predisposing factor in the neurobehavioural toxicity of styrene.

PMID- 7822685
TI  - Teratological assessment of stobadine after single and repeated administration in
      mice.
AB  - Teratological studies were performed with stobadine, a compound with
      antiarrhythmic and antihypoxic activity. Single i.v. injections of stobadine in
      the form of dihydrochloride (DH 1011) to ICR mice on days 3, 6, 9 or 12 of
      gestation at doses of 1 and 3 mg kg-1 had no teratogenic effect. Slight fetal
      toxicity was manifested by decreased fetal weight after treatment on days 3 and
      6, increased incidence of rudimentary ribs after treatment on days 9 and 12 of
      gestation and non-significantly increased postimplantation loss after injection
      on day 6 of gestation. The effect of repeated oral administration in the form of
      dipalmitate salt (DP 1031) was studied in doses of 12.2, 61.0 and 122.0 mg kg-1
      on days 4-16 of gestation. Oral exposure to 61.0 mg kg-1 DP 1031 resulted in
      significant reduction of implantations, live fetuses and litter weight, and after
      122.0 mg kg-1 DP 1031 the fetal weight was significantly decreased. External and
      skeletal examinations of the fetuses revealed no evidence of teratogenesis. The
      relevance of the two routes of stobadine administration for risk involvement is
      discussed.

PMID- 7822686
TI  - Method for preserving erythrocytic delta-aminolevulinic acid dehydratase activity
      that facilitates population studies on lead intoxication.
AB  - A method preserving the activity of the erythrocytic enzyme delta-aminolevulinic
      acid dehydratase (EC 4.2.1.24) was developed using a vehicle of 50% aqueous
      glycerol containing dithiothreitol (80 microM). Whole heparinized blood (0.5 ml)
      was added to 0.75 ml of this mixture in a cryovial tube (capacity 1.3 ml), mixed
      well and stored in a freezer at -20 degrees C for 21 days. Statistical comparison
      of the enzyme activity when freshly assayed and after storage indicated excellent
      agreement for quantitation of the non-activated enzyme (intraclass correlation
      coefficient = 0.99) and the activated enzyme (intraclass correlation coefficient
      = 0.98). This storage method will facilitate future population studies on lead
      intoxication, particularly those in remote locations.

PMID- 7822687
TI  - Ex vivo technique for evaluating the effect of chemical vapours on mucociliary
      activity.
AB  - An experimental protocol has been developed for the use of rat tracheal explant
      to evaluate the effects of inhaled chemicals on the mucociliary function. Rats
      were exposed for 4 h or 7 days (24 h per day) to different concentrations of
      toluene diisocyanate (TDI). Each rat trachea was subsequently removed rapidly and
      placed in a humid chamber maintained at 37 degrees C. Mucociliary function was
      evaluated by video measurements of the two following parameters: mucociliary
      beating frequency (MCBF) and number of active (A+), partially active (A +/-) and
      inactive areas (A-). In control tracheas; all areas were active and the MCBF
      showed hardly any variation around 15.3 Hz. In rats exposed to ca. 0.27 or 0.54
      ppm of TDI for 4 h, tracheas showed a significant decrease in the number of
      active areas and a significant decrease in the MCBF. The same changes were
      observed in tracheas from rats exposed to approximately 0.05 and 0.10 ppm of TDI
      for 7 days. After a 7 days recovery period the number of active areas and the
      MCBF were similar in exposed and control rats except in the group exposed for 7
      days to the highest concentrations; these showed only partial recovery. The
      results of this study showed that this ex vivo method is useful for detecting
      mucociliary dysfunction.

PMID- 7822688
TI  - Nickel hydroxy carbonate increases tumour necrosis factor alpha and interleukin 6
      secretion by alveolar macrophages.
AB  - The aim of the current study was to assess the in vitro effects of nickel hydroxy
      carbonate (NiHC) at noncytotoxic concentrations on the production of cytokines
      such as tumour necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) in
      alveolar macrophages (AMs). The effect of NiHC was evaluated in both unstimulated
      AMs and cells activated by lipopolysaccharide (LPS). Cytotoxicity was related to
      lactate dehydrogenase release and ATP cell content. The results confirm that NiHC
      at concentrations of 0.125, 1.25 and 3.125 micrograms NiHC 10(-6) cells was not
      cytotoxic. The NiHC exposure of unstimulated AMs significantly increased the
      release of TNF-alpha at all concentrations and that of IL-6 at 1.25 micrograms
      NiHC 10(-6) cells. LPS addition significantly increased the secretion of both
      cytokines. However, NiHC did not cause a significant increase in the release of
      TNF-alpha and IL-6 in LPS-stimulated cells. In conclusion, the ability of NiHC to
      activate AMs and to release increased amounts of pro-inflammatory mediators may
      be responsible, at least partly, for inflammation and pneumotoxicity associated
      with nickel exposure.

PMID- 7822689
TI  - Oxidant radical release by alveolar macrophages after cadmium chloride exposure
      in vitro.
AB  - Chronic exposure to cadmium can cause lung emphysema, the mechanism of which is
      unknown. Current concepts on the pathogenesis of emphysema largely emphasize the
      role of a protease-antiprotease imbalance. The aim of this work was to study the
      effects of cadmium on the regulation of antiprotease activity and the release of
      oxidant radicals from alveolar macrophages. Guinea pig alveolar macrophages (AM)
      were exposed overnight to cadmium chloride (CdCl2) in vitro. To define the
      cytolytic threshold dose, cell lysis was evaluated by trypan blue exclusion and
      lactate dehydrogenase release. Non-cytolytic concentrations were then used (0.1,
      0.4 and 0.8 ppm) to simulate chronic exposure conditions. Overnight exposure to
      0.1, 0.4 and 0.8 ppm CdCl2 decreased intracellular ATP (mean +/- SD: 91 +/- 8%,
      72 +/- 7%, 50 +/- 8% of control cells, respectively), suggesting that even at non
      cytolytic doses, Cd2+ can cause cell injury. The assessment of oxygen radical
      release from AM after overnight exposure to CdCl2 showed a dose-dependent
      decrease to 54.3 +/- 8.2%, 32.2 +/- 4.3% and 25 +/- 3% of control after exposure
      to 0.1, 0.4 and 0.8 ppm Cd2+, respectively. At non-cytolytic concentrations (0.1,
      0.4 and 0.8 ppm) CdCl2 did not decrease alpha 1-proteinase inhibitor activity
      either in the absence of AM or in the presence of AM and myeloperoxidase. In
      conclusion, our in vitro results do not suggest that a protease-antiprotease
      imbalance is involved in the pathogenesis of cadmium-induced emphysema.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7822690
TI  - Two-generation reproduction study on commercial hexane solvent.
AB  - The reproductive effects of inhalation exposure to commercial hexane vapors were
      evaluated in Sprague-Dawley rats. Males and females were exposed to commercial
      hexane vapor at target concentrations of 0, 900, 3000 or 9000 ppm for 6 h a day,
      5 or 7 days a week, over two generations. In addition to pre-breed exposures of
      10 weeks' duration, exposures continued through mating, gestation and lactation.
      At both the F0 breed to produce F1 litters and the F1 breed to produce F2
      litters, reproductive parameters were unaffected by commercial hexane exposure.
      The mating, fertility and gestational indices, as well as litter size and
      postnatal survival, were not significantly different between exposure groups.
      However, reductions in body weight and body weight gain were observed in both F1
      and F2 litters exposed to 9000 ppm. Effects on body weight were not observed in
      offspring exposed to the two lower concentrations of commercial hexane.
      Histopathological examination of selected tissues revealed hyaline droplet
      nephropathy in adult F0 and F1 males exposed to 9000 ppm. This finding was
      anticipated and is not believed to be relevant for the assessment of human health
      effects. No other treatment-related histopathological lesions were observed.
      Thus, exposure of rats to commercial hexane for two generations resulted in
      reduced body weight gains at 9000 ppm but no adverse effects on reproduction.
      These findings suggest that occupational exposure to commercial hexane vapors at
      currently recommended threshold limit value concentrations (i.e. TLV for n-hexane
      is 50 ppm and TLV for other hexane isomers is 500 ppm) should not pose a
      reproductive hazard.

PMID- 7822691
TI  - [Bouchut tubercles and AIDS. Apropos of 3 cases].
AB  - Tuberculosis choroidal granulomas ("tubercules de Bouchut") are rare, even in
      patients with AIDS and active tuberculosis. The authors report the clinical and
      angiographical findings of three cases. Choroidal involvement was bilateral, with
      multiple lesions, mostly located at the posterior pole. The size of the granuloma
      ranged from 1/8 to 1/2 of a disc diameter. Fluorescein angiography showed early
      prolonged hypofluorescence and late moderate hyperfluorescence. The lesions
      remained stable for months despite treatment of tuberculosis, and then gradually
      subsided. In two cases, the choroidal granulomas were discovered before the
      diagnosis of disseminated tuberculosis and guided the investigations, which
      allowed the identification of Mycobacterium Tuberculosis bacillus in the body. In
      the third case, pulmonary tuberculosis had already been diagnosed. The number of
      tuberculosis cases is increasing together with the number of AIDS cases. This
      should make the observation of tuberculosis choroidal granulomas more frequent.
      The discovery of the typical aspects of granulomas described above during fundus
      examination of AIDS patients can help in diagnosing tuberculosis.

PMID- 7822692
TI  - [Transcanalicular endodacryocystorhinostomy using Neodymium:YAG laser].
AB  - We describe a new technique of dacryocystorhinostomy (DCR) and we present our
      first clinical cases. The principle of this technique is to create a fistula
      between the lacrimal sac and the nose with a quartz fibre advanced through a
      canaliculus and connected to a Neodymium:YAG. TECHNIQUE: An 800 microns outer
      diameter metallic pipe was inserted through a lacrimal canaliculus up to bone
      contact. An optical fibre light probe was inserted through the pipe in order to
      locate the lacrimal sac in the nasal fossa by translumination using a nasal video
      endoscope. The optical fibre light probe was then replaced with a laser fibre and
      a lacrimo-nasal fistula (approximately 5 mm diameter) was created in a few
      minutes by juxtaposition of twenty or more 10 watt energy pulses. Finally, a
      silicone stent was positioned for 6 months. MATERIAL AND METHOD: We have operated
      41 DCR using this transcanalicular method with the Nd:YAG laser. Our mean follow
      up was 6 months (max 16 months). Indications were stenosis of the naso-lacrimal
      duct, failed classical DCR, abscesses of the lacrimal sac uncurable by
      antibiotherapy and canaliculary stenosis. RESULTS: Success rate was 75%, both for
      primary procedures and for operations after failed classical DCR. CONCLUSION: The
      advantages of this method are its simplicity, its atraumatic feature, minimal
      bleeding, the absence of scar and its ability to treat obstructions located at
      all levels of the excretory lacrimal system. Minimal operating traumatism makes
      it a very convenient method for out patient clinic.

PMID- 7822694
TI  - [Treatment of coloboma pitS of the optic nerve complicated by serous detachment
      of the neuroepithelium].
AB  - PURPOSE: The pathogenesis of the sensory retinal detachment of the macula
      associated with congenital pit of the optic nerve remains controversal. Based on
      our cases and the cases reported in literature, we propose a management plan for
      macular retinal detachment associated with optic nerve pit. METHODS: In this
      retrospective study ten eyes were treated for progressive visual loss. Treatment
      modalities were different depending on the time period: laser photocoagulation
      (to the juxtapapillary region) alone, laser combined with intraocular gas
      injection (C3 F8), laser combined with vitrectomy and intraocular gas tamponnade
      (S F6, C3 F8), laser combined with vitrectomy and temporary silicone oil
      tamponade. RESULTS: The follow-up period ranged between one and five years (mean
      follow-up thirty three months). We had eight successes and two definitive
      failures (an old macular detachment treated only by one laser session, and a
      young girl who had not kept the prone position after gas injection). In the group
      of six eyes treated by laser alone, only two retinal treatments were directly
      successfully treated; in three other eyes, the detachment recurred and was
      treated with success in a second step by a gas injection; the sixth eye is the
      first definitive failure (old detachment). In the five eyes treated by laser
      combined gas injection with or without pars plana vitrectomy (including three
      failures of laser alone), the retina remained attached in four eyes during the
      follow-up period; the sixth eye was the second definitive failure (the young
      girl). In the both eyes treated by vitrectomy and silicon oil injection, the
      retina has flattened. CONCLUSION: The results suggest that laser photocoagulation
      alone is not so efficient and that vitrectomy is not necessary with gas
      injection. Complete resorption of subretinal fluid occurred in eight eyes: two
      with laser photocoagulation alone, and six with a long term tamponnade combined
      with a peripapillary laser photocoagulation. In first treatment, this technique
      (laser with tamponade) is a valuable approach to manage serous macular detachment
      associated with optic nerve pit.

PMID- 7822693
TI  - [Severe keratomycosis. Diagnosis and treatment].
AB  - We reported three consecutive cases of severe fungal keratitis initially
      undiagnosed by corneal scrapping. Corneal biopsy showed fungal elements of
      Paecilomyces lilacinus, Fusarium solani, Scedosporium apiospermum. Most cases of
      fungal keratitis could be treated successfully if adequate antifungal therapy
      were started early. Early and accurate diagnosis is of major importance. The
      results of our cases confirm the superiority of corneal biopsy over corneal
      scrapping. Corneal biopsy is a procedure of choice in suspected cases of
      keratomycosis in which corneal scrapings fail.

PMID- 7822695
TI  - [Retinal detachment after surgery of congenital cataract].
AB  - We conducted a retrospective study of retinal detachments after congenital
      cataract surgery managed during the last twelve years so as to determine whether
      the surgical prognosis has been improved by the use of vitreoretinal
      microsurgery. The study included 25 eyes of 23 consecutive patients. The time
      interval between cataract surgery and the onset of retinal detachment ranged from
      1 month to 46 years. It was 10 to more than 30 years in 60% of patients. Fourteen
      patients (60.8%) were over 26 years old. Nine eyes (36%) showed PVR grade B to
      D3. Preoperative fundus examination was hindered by anterior segment changes
      secondary to cataract surgery in 18 eyes. Microsurgical management included
      reconstruction of the anterior segment via the pars plana in 7 eyes, vitrectomy
      in 10 eyes, gas injection in 15 eyes and the use of liquid perfluorocarbon in 1
      eye. Anatomic success with at least a six month-follow-up was achieved in 22 eyes
      (88%). It is concluded that the surgical prognosis of retinal detachment after
      congenital cataract surgery has been improved by modern vitreoretinal
      microsurgery.

PMID- 7822696
TI  - [Treatment of diabetic macular edema with neuroepithelium detachment combining
      high-dose corticotherapy and photocoagulation].
AB  - The clinical course of background diabetic retinopathy in its oedematous form
      (macular and diffuse posterior pole edema), leads to serous macular retinal
      detachment. At this stage, even if the laser burns are observed on the retinal
      pigment epithelium, laser photocoagulation is unsuccessful in such a serous
      detachment, because retinal neuroepithelium is far from the retinal pigment
      epithelium. We have previously noticed that high doses of oral steroid drug (one
      milligram per kilo a day) for fifteen days may allow a partial or complete
      macular flattening. This flattening is only correctly evaluated by contact glass
      biomicroscopy, and often associated to a visual improvement. Favourable outcome
      was observed in 76% of the fifty-eight eyes, which have been laser treated. When
      laser photocoagulation was successful, the results were stable with an
      improvement of two or four lines. If flattening did not occur, laser
      photocoagulation was not performed. Oral steroids treatment for long-term insulin
      treated diabetic patients required a very close daily diabetic or/and internist
      survey. At our institution, it was possible because the internist was at the
      patient's bed once or twice a day: for this reason, this technique seems to be
      the first study in the literature. Some very unexpected visual improvements
      incite us to use classic laser treatment as early as possible for macular or
      diffuse posterior pole oedema, before a serous retinal detachment occurs and
      renders treatment impossible excepted with the help of high doses steroids.

PMID- 7822697
TI  - [Course of trachoma under treatment with 1% oxytetracycline ophthalmic solution].
AB  - PURPOSE: In order to optimize the trachoma treatment duration, we carried out a
      prospective study to observe the disease course over a long period of treatment
      by a 1% oxytetracycline (chlorhydrate) suspension. METHODS: The study involved 50
      children between 2 and 12 years living in three Malian villages. The existence of
      an active trachoma was clinically characterized by the presence of at least 5
      follicles associated with a papillary hypertrophy of the upper tarsal
      conjunctiva. The treatment was administered daily 4 times a day, for two months.
      All patients were examined before being treated, then on the 15th, 30th and 60th
      day. The presence and the importance of the follicles, papillae and trachomatous
      scarring were scored. During treatment, no patient manifested a case of
      follicular score aggravation. The moderate cases reacted more rapidly than the
      severe ones. In most cases the reduction in the number of follicles became
      evident only after two weeks of treatment. On the other hand, the inflammatory
      hyperplasia diminished rapidly from the 15th day. The cicatricial score was
      constant and pre-existing scars were not aggravated. After treatment, 33 patients
      out of 50 (66%) could be considered cured. CONCLUSION: The analysis of data
      suggests that a longer period of treatment would have led to a higher healing
      percentage. In fact, all forms of intense trachomatous inflammation, likely to
      cause blindness, diminished before the end of the control period.

PMID- 7822698
TI  - [J.J. a daltonic painter].
AB  - Mr. J.J., painter, has been a professional artist for thirty years. On clinical
      examination of the color vision by pseudo-isochromatic plates, City University
      Colour Vision Test, standard and desaturated Panel-D 15, Farnsworth 100-hue test
      and Nagel's anomaloscop evidenced a typical hereditary deuteranopia. Neverless,
      the recognition and the denomination of coloured samples, presented singly or in
      simultaneous chromatic contrast, evidenced only a few errors. In an interview,
      the subject explained his difficulties with colours, mainly with green, and the
      procedures used to avoid mistakes in painting: knowledge of the names of colors
      written on tubes; precise order of arranging the tubes; use of a palette
      restricted to some basic hues, avoiding green. The subject artistic technique is
      based on drawing, on better perceived colours (i.e. the blues) and on value
      contrasts. He also enumerated his difficulties with colours in casual situations:
      clothes, traffic, food. Some reproductions of the works of the painter illustrate
      this study.

PMID- 7822699
TI  - [Central retinal artery occlusion in surgery of the cervical vertebrae].
AB  - Retinal artery occlusion related to ocular compression is an uncommon but severe
      complication of general anaesthesia, most of the time results in blindness. We
      report a case of central retinal artery occlusion following spinal surgery. We
      discuss the mechanism of blindness and review the circumstances that may lead to
      this complication. Proper positioning of the head and avoidance of ocular
      compression will prevent the occurrence of retinal occlusion during general
      anaesthesia.

PMID- 7822700
TI  - [Orbital mucocele].

PMID- 7822701
TI  - [Immature palpebral capillary angioma. A case commented on].
AB  - A three-year-old girl presented a voluminous capillary haemangioma associated
      with amblyopia. This case failed to respond to steroid treatment. Surgical
      treatment was necessary. The authors describe evolution, complications and
      therapeutic management of eyelid angiodysplasia.

PMID- 7822702
TI  - [Caruncular site of pyogenic granuloma. Apropos of an anatomo-clinical case].
AB  - A clinico-pathologic case of a pyogenic granuloma is reported in a 34-year-old
      male patient. Clinically, a nodular painless reddish tumour with a fibrinous
      membrane covered top, developed at the right caruncle. After surgical excision,
      the histopathological study established the diagnosis of a pyogenic granuloma,
      partially covered by a conjunctival epithelium, and a fibrinous membrane at its
      top.

PMID- 7822703
TI  - [Controversies in the pathogenesis and medical treatment of thyroid
      ophthalmopathy].

PMID- 7822704
TI  - [Complication during cataract surgery: how to continue the operation?].

PMID- 7822705
TI  - [Tamoxifen in the treatment of breast cancer].
AB  - Tamoxifen is the most often prescribed non steroidal antioestrogenic agent in the
      world for breast cancer. Worldwide collaboration. has centralized the results, of
      different trials throughout the world on oral adjuvant therapy in the early
      stages of breast cancer. A significative regression of the tumour was observed in
      most cases. Moreover, recent epidemiological studies suggest that tamoxifen could
      prevent new contralateral primary tumours. The risk of the disease should thus be
      reduced by the prophylactic use of antioestrogens such as tamoxifen.
      Investigations using a variety of models have evaluated the effect of tamoxifen
      on tumour promotion and cell growth. Tamoxifen-induced growth inhibition is
      associated with major changes in biochemical events in cultured human breast
      cancer cells including cell proliferation or growth factor production. Growth
      inhibition of oestrogen-responsive human breast cancer cells is associated with
      an induced secretion of autoinhibitory polypeptides (TGF beta) and an
      antagonistic effect on the synthesis of proliferative proteins (TGF alpha,...).
      The first step in the mechanism of action of the drug is binding of tamoxifen to
      the oestrogen receptors. Development of resistance to tamoxifen treatment is a
      great problem in treatment of breast cancer patients and the mechanism of
      resistance will require further study: under the influence of the drug, tumours
      could become remodelled as selected subpopulations emerge resistant-tamoxifen.
      The fact that some breast cancers which are oestrogen receptor-negative respond
      to antioestrogen suggests that parallel but separate pathways for oestrogen and
      antioestrogen action may exist. This paper summarizes the results of the most
      recent studies concerning this promising drug.

PMID- 7822706
TI  - [The endothelium of the corpus cavernosum].
AB  - Recently, it has been demonstrated that the endothelium of corpus cavernosum
      plays an important role in the physiology of erection. Endothelial cells
      synthesize and release constricting and relaxing factors. These factors are
      essentially represented by endothelin and nitric oxide. Endothelin is a peptide
      generated by endothelial cells with potent vasoconstrictor properties. This
      peptide provokes more sustained constriction of corpus cavernosum smooth muscles
      than noradrenaline. This effect suggested that endothelin may play a role in the
      regulation of tone in penile vascular and cavernous tissues in man. In addition,
      recent experimental studies showed an important role of nitric oxide for
      cavernous smooth muscle relaxation. This factor may act as an inhibitory
      neurotransmitter in penile corpus cavernosum smooth muscle. The characteristics
      of these substances are reviewed.

PMID- 7822707
TI  - [Delay of the formation of retroperitoneal fibrosis after lymphadenectomy. An
      experimental study].
AB  - The goal of our study was to evaluate peritoneal and retroperitoneal healing and
      therefore to assess the optimal date for surgery after laparoscopic
      lymphadenectomy. A para-aortic lymphadenectomy was carried out in 5 groups of 5
      New Zealand female rabbits. The perivascular cicatricial tissue was dissected
      after specific delay for each group (48 hours, 1 week, 2 weeks, 4 weeks, and 6
      weeks). Peritoneal reconstruction was observed in 80% of the "48 h" group, and in
      100% in the other groups (from 1 to 6 weeks). Vascular injury complicated
      dissection in 40% for the "1 week" group, in 80% for the "2 weeks" group, and in
      20% for the "6 weeks" group. No vascular complication was observed in the "48 h"
      and "4 weeks" groups. The results of "1 week" and "2 weeks" were combined. The
      results of the "4 weeks" group were compared, with the Fisher test, to the
      results of a "1 week" and "2 weeks" combined group as well as to the results of
      the "six weeks" group. Four weeks seem to be the optimal date for a possible
      surgical excision after a laparoscopic lymphadenectomy.

PMID- 7822708
TI  - [Transvaginal pulsed color Doppler ultrasound in the study of the menstrual
      cycle].
AB  - Pulsed colour-Doppler imaging in the latest development in transvaginal
      sonography. Our objective is to study the uterine and ovarian perfusion during
      the menstrual cycle in normal fertile conditions. We studied 11 healthy volunteer
      women free of hormonal treatment. All studies were performed by the same
      operator, with the same sonograph. Measurements are made in the uterine arteries
      and their branches (arcuate, radial, spiral arteries) and in the ovarian vessels.
      The resistance index of Pourcelot (RI = [sequence: see text]) is used as
      reference. The statistic test is the non-parametric test of Kruskall-Wallis. The
      uterine and ovarian vascularization varied greatly during the menstrual cycle.
      Blood flow increased significantly in the luteal phase in the uterine arteries
      and their branches even in the active ovarian arteries. So, in the uterine
      artery, the RI was 0.43 in the follicular phase, 0.50 during the ovulatory peak,
      and 0.41 in the luteal phase. These variations were significant (p = 0.04). These
      results were the same all along the uterine artery. In the acurate arteries, the
      RI was respectively 0.75, 0.93, 0.72 at the same time of the menstrual cycle (p =
      0.04). In an anovulatory cycle, blood flow remained unchanged and the arterial
      compliance remained stable. Quick and reproductible blood flow measurements are
      possible with transvaginal colour-Doppler. Millimetric vessels such as arcuate,
      radial and spiral arteries can be studied. This non-invasive technology can be
      used as a part of routine work in the management of infertility.

PMID- 7822709
TI  - [Laparoscopically-prepared vaginal hysterectomy. Our personal experiences
      (apropos of 35 cases)].
AB  - We report our personal experience with 35 laparoscopically prepared vaginal
      hysterectomies performed over a 3 year period, for January 1990 to January 1993.
      We give our indications for this new technique present our results. We compared
      our results with those reported in the literature evaluating indications,
      technique and complications and demonstrate the numerous advantages of this new
      technique. Finally, a decision protocol has been prepared in order to chose the
      optimal approach according to the preoperative work-up.

PMID- 7822710
TI  - [Ovarian hyperstimulation syndrome and thrombosis. Apropos of a case of
      thrombosis of the internal jugular vein. Review of the literature].
AB  - Thrombosis of the internal jugular vein was associated with a severe syndrome of
      ovarian hyperstimulation. After in vitro fertilization, a twin pregnancy was
      obtained in a 31-year-old patient with severe endometriosis. On the day of
      follicle collection, plasma oestradiol was 3050 mg/ml. Ten ovocytes were
      collected and 3 embryos were implanted. A syndrome of severe ovarian
      hyperstimulation (ascites, pleural effusion) developed 3 weeks later and
      symptomatic treatment was given. Phlebitis of the upper left limb was diagnosed
      at 9 weeks amenorrhoea and echo-Doppler confirmed the diagnosis of subclavian and
      internal jugular venous thrombosis. Search for a cause was negative excepting a
      frank drop in protein S activity to 35%. Post-partum assay and assay in family
      members confirmed that the deficiency was acquired during pregnancy. The clinical
      course was favourable with anticoagulant therapy (heparin, then low-molecular
      weight heparin). Intra-uterine death of one of the fetuses occurred at 21 weeks
      amenorrhoea and a 2,550 g girl was born by vaginal delivery at 36 weeks. The
      Apgar score at birth was 10/10. In a review of the literature on vascular events
      in fertilization, programmes showed that severe syndromes of ovarian
      hyperstimulation, endogenous hyperestrogenism, multiple pregnancy and
      predominance of upper limb are the most frequently observed criteria. We
      emphasize the importance of preventing these thromboembolic events with
      subcutaneous heparin during the first trimester of pregnancy followed by low
      molecular weight heparin, particularly in patients with a history of
      thromboembolism and/or patients with severe ovarian hyperstimulation.

PMID- 7822711
TI  - [Laparoscopic treatment of ovarian tumors in menopausal women].
AB  - OBJECTIVE: The authors report their experiences in the laparoscopical therapy of
      ovarian tumours with 94 postmenopausal women. STUDY DESIGN: The patients were
      treated in the Department of Gynecology at Goppingen Medical Center from March 1,
      1992 until December 31, 1993. Tumour marker CA 125 was not within normal limits
      (< 35 U/ml) in all patients. Preoperatively all findings were verified by
      ultrasound examination. In some cases, cysts were single-chambered, smooth
      bounded or without endovegetations. Choice therapy has been bilateral adnectomy
      without opening the ovarian cyst and without trauma to the ovary capsula.
      Adnectomy was performed by bipolar coagulation and sharp preparation. In every
      case the specimen was positioned intact in a "Lap-Sac" and then removed via
      second puncture. In case of ultrasonographic or laparoscopic-macroscopic
      conspicuous findings an obligatory fast microscopic random sample was performed.
      RESULTS: In one case the microscopic test sample revealed carcinoma of the ovary-
      the operation was terminated by standard laparotomy. No other cases showed signs
      of malignancy. There were no peri- or postoperative complications. The average
      operation lasted 35 min (20-80 min), all operations were performed without
      significant blood-loss. Usually the patients were discharged at the 4th to 6th
      postoperative day. CONCLUSION: This operation-technique guaranteed "oncological
      aseptic" results at any time of operation. Therefore you can waive the standard
      laparotomy for the benefit of laparoscopy in many elderly patients even with
      suspicious findings.

PMID- 7822712
TI  - [Immature teratoma of the ovary. Apropos of 3 cases. Review of the literature and
      an evaluation].
AB  - Immature teratoma of the ovary is a rare tumour (1% of cancer of the ovary)
      usually seen in adolescents or young women. It is a malignant tumour derived from
      an abnormal germ-cell which undergoes meiotic division. The diagnosis is based on
      the pathological examination which reveals immature tissue derived from two or
      three types of embryonic tissue (endo-, meso- and ectoderm). Intraperitoneal
      dissemination occurs and immature or mature recurrence is observed. The prognosis
      was particularly severe before the use of polychemotherapy which has also made
      conservative surgery possible. At the present time, the consensus is to reduce
      the duration of the chemotherapy with a regular clinical and laboratory (tumour
      markers, aFP) monitory. A second look laparotomy verifies successful treatment.

PMID- 7822713
TI  - [Primary malignant lymphoma of the uterine body. Apropos of a case and review of
      the literature].
AB  - We observed a case of primary malignant lymphoma located in the uterine body
      which was discovered fortuitously after hysterectomy in a 75-year-old patient who
      suffered from post-menopausal bleeding. Search for extension did not reveal extra
      genital involvement. This localization is exceptional and only 7 cases have been
      reported in the literature. The most frequent histological type is diffuse large
      cell lymphoma. Surgical treatment is indicated with possible secondary
      radiotherapy and/or chemotherapy depending on the clinical presentation.

PMID- 7822714
TI  - [Langerhans-cell histiocytosis in an adult with initial vulvar involvement: 2
      cases].
AB  - Langerhans' histiocytosis is a proliferation of atypical Langerhans cells which
      may affect several different organs. Two women had lesions of the vulva which led
      to the diagnosis. Vulvular involvement is the most frequent in gynaecological
      localization of Langerhans' histiocytosis. Pathological and immunohistochemical
      tests confirm the diagnosis.

PMID- 7822715
TI  - [Pruritus specific to pregnancy].
AB  - Many pregnancies are complicated by a pruritus. A study of the liver functions,
      including a determination of plasma bile acids, and a biopsy of each doubtful
      dermatological lesion with direct immunofluorescence allow to distinguish the
      specific pruritic diseases of the pregnancy: pemphigoid gestationis, papulous and
      pruritic dermatitis and cholestasis of pregnancy. The pemphigoid gestationis is
      an autoimmune bullous acquired dermatosis, which recurs at each pregnancy; a
      positive direct immunofluorescence is specific of the disease; the fetal
      prognosis seems to be good; a systemic corticotherapy is necessary. The papulous
      and pruritic dermatitis are the most common dermatosis during the gestation: the
      maternal and fetal prognosis are excellent, but this diagnosis remains a
      diagnosis of elimination. The cholestasis of pregnancy is characterized by an
      isolated pruritus which rapidly disappears in the postpartum period; its
      pathogeny probably includes many factors, but it seems to be favoured by a
      genetic ground; the determination of plasma bile acid, even if it is not
      specific, leads toward the diagnosis. The mother often requires an aggressive
      symptomatic treatment but the delivery can be delayed till the pulmonary maturity
      is obtained.

PMID- 7822716
TI  - [Non-steroidal anti-inflammatory agents and pregnancy. A study of renal and
      digestive toxicity of niflumic acid in the perinatal period].
AB  - We report a case of intrauterine exposure to niflumic acid in a preterm neonate
      (35 weeks of gestation). The mother received niflumic acid (750 mg daily) during
      the last four days of gestation. Severe oligohydramnios was present. A transient
      neonatal renal failure, but also abdominal complications were observed for
      several days. Maternal and neonate niflumic acid levels were studied and showed
      an important placental transfer. Niflumic acid is a prostaglandin synthetase
      inhibitor. It is important that the nephrotoxicity of this vasoactive drug be
      known. Maternal administration of niflumic acid during the last days of gestation
      can induce fetal and neonatal adverse effects, especially renal failure.
      Prescription of all nonsteroidal anti-inflammatory drugs must be very cautious
      during pregnancy.

PMID- 7822717
TI  - [Cerebral complication in eclampsia].
AB  - Many brain complications occur during eclampsia with various degree of gravity.
      The pathogenesis of these lesions continues to be a source of considerable
      controversy. Five cases of eclampsia with severe neurologic manifestations were
      treated in our surgical intensive care unit. The CT image appeared to be related
      to haemorrhagic lesions (3 cases) and ischaemic lesions (2 cases). The clinical
      course was favourable, often reversible, in cases with oedema and ischaemia
      maternal prognosis was poor in the case with haemorrhage.

PMID- 7822718
TI  - [The value of anatomo-pathologic examination of the placenta in areas of endemic
      malaria and low socio-cultural levels].
AB  - OBJECTIVES: Determine the sensitivity of the pathology examination of the
      placenta as a screening examination for malaria and the consequences of this
      infection on prematurity and birth-weight. METHODS: Eighty placentas were
      examined at the Mjunga, Madagascar dispensary at the beginning of the rainy
      season. The aspect of the placenta was compared with a malaria index and to
      malaria disease state as a function of parity and anti-malarial prophylaxis used
      by the mother as well as with the state of the infant. RESULTS: Among the
      placentas examined, 41.3% were considered normal and abnormal or clearly
      pathological in 58.7%. Estimating the gestational age on the basis of the
      histological examination of the amniotic cells was in agreement with the
      gestational age calculated from the last cycle in 53 cases and in disagreement in
      8 cases. The percentage of cases of malaria discovered by the pathology
      examination (20%) was greater than that after thick swab screening (10%). 75% of
      the mothers has Plasmodium falciparum infection at the time of delivery and 13.8%
      of the mothers with negative thick drops had malaria lesions of the placenta. The
      parity of infected mothers was similar to non infected mothers. All the premature
      newborns had pathological placentas included 12.5% with malarial lesions. 90% of
      the hypertrophic newborns had pathological placentas included 50% with malarial
      lesions. No case of congenital malaria was observed. CONCLUSION: Pathology
      examination of the placenta is as sensitive as blood drop tests for screening for
      malaria. The histological examination of amniotic cells can give a good
      estimation of gestational age in developing countries.

PMID- 7822719
TI  - [Returning the fetus to the family for the purpose of burial].

PMID- 7822720
TI  - [Did the Romans know about forceps?].

PMID- 7822721
TI  - [Is systematic examination using uterine revision of the anterior segment
      cesarean section scar justified after a successful uterine test?].

PMID- 7822722
TI  - Molecular genetics: what's left for clinicians?

PMID- 7822723
TI  - Basal ganglia: functional anatomy and physiology. Part 2.
AB  - Advances in knowledge about basal ganglia function and circuitry are reviewed.
      Despite the voluminous available literature on this subject, the role of basal
      ganglia in health and disease remains controversial. Experimental data on the
      effects of stimulation and ablation of the basal ganglia are summarized. The
      roles of the basal ganglia in the preparation for and execution of cortically
      initiated movement are described. Newer roles ascribed to the basal ganglia in
      sensory-motor gating, cognition, emotion, and motivation are discussed. The old
      and current concepts of information flow between the cerebral cortex, striatum,
      pallidum, thalamus, and back to the cerebral cortex are reviewed. The "funnel"
      system of information flow has been discarded in favor of several parallel and
      largely segregated loops pertaining to motor, oculomotor, cognitive, and limbic
      functions. The anatomic substrate of each of these loops is described. The
      specific roles of the striatum, pallidum, substantia nigra, and thalamus in
      information flow as related to movement are described. The roles of the basal
      ganglia in reinforcing wanted behavior and suppressing unwanted behavior via
      direct and indirect striatal loops are discussed. The implications of these loops
      in the genesis of Parkinson's disease and Huntington's chorea are described.
      Alteration in basal ganglia neurotransmitters and neuromodulators in Huntington's
      chorea, Tourette's syndrome, and Parkinson's disease are described.

PMID- 7822724
TI  - Electrodiagnosis of infantile botulism.
AB  - Analysis of the literature on the electrophysiologic features of infantile
      botulism was undertaken. Small compound muscle action potential amplitude is a
      very sensitive feature but lacks specificity. The decremental response to 2- to 3
      Hz repetitive nerve stimulation is inconsistent and not a reliable sign. Tetanic
      and posttetanic facilitation are highly sensitive and highly specific. Absence of
      posttetanic exhaustion is also highly specific for infant botulism and shared
      only by hypermagnesemia. We conclude that the findings of low compound muscle
      action potential amplitude in combination with tetanic facilitation or
      posttetanic facilitation and absence of posttetanic exhaustion constitute the
      triad on which the electrodiagnosis of infantile botulism can be supported.

PMID- 7822725
TI  - Tolstoy's description of Tourette syndrome in Anna Karenina.

PMID- 7822726
TI  - Neuropsychological profile of children with neurofibromatosis, brain tumor, or
      both.
AB  - Neurofibromatosis type 1, a common autosomal dominant genetic disorder, is
      associated with numerous physical and medical anomalies as well as an increased
      incidence of learning disability. Tumors of the central nervous system have been
      estimated to occur in 15%, but their contribution to neuropsychological status is
      unknown. This study examines the relative contribution of neurofibromatosis and
      brain tumor to the cognitive profile of children with neurofibromatosis. A
      comprehensive battery of neuropsychological and behavioral tests was administered
      to a group of 65 children with neurofibromatosis type 1. Fourteen were then
      matched on demographic variables with two other groups of children who had either
      a brain tumor in addition to neurofibromatosis or a brain tumor alone. The two
      brain tumor groups were also matched on tumor type, location, and therapy. Mean
      scores of the neurofibromatosis-brain tumor group were generally the lowest of
      the three groups; those of the brain tumor group were highest, and performance of
      the neurofibromatosis group was generally between the other two groups. These
      results suggest that neurofibromatosis is, by itself, associated with significant
      cognitive morbidity, but that the severity of the problems is increased somewhat
      if a brain tumor is also present.

PMID- 7822727
TI  - Use of a calcium channel blocker (nicardipine HCl) in the treatment of childhood
      moyamoya disease.
AB  - Moyamoya disease is a cerebrovascular disease characterized radiologically by
      progressive narrowing and occlusion of the arteries contributing to the circle of
      Willis and its branches. There is formation of an exuberant collateral network of
      blood vessels at the base of the brain, which is thought to arise in response to
      chronic ischemia. Clinically, the course is variable, with patients having
      repeated transient ischemic attacks, strokes, migraine, and seizures. Effective
      treatment is not available. The etiology and pathophysiology of moyamoya disease
      are largely unknown. Two patients with arteriographically proven moyamoya disease
      were identified. Both patients were symptomatic before age 5 years. Despite
      successful encephaloduroarteriosynangiosis revascularization procedures, they
      continued to experience an inexorable downhill course. A calcium channel blocker
      (nicardipine HCl) was introduced in order to prevent further symptoms. After the
      introduction of nicardipine, no further strokes occurred in either patient. There
      were no further episodes of transient ischemic attacks, seizures, or headache in
      one patient and decreased frequency in the other. In patients with moyamoya
      disease, nicardipine may have a beneficial effect on cerebral hemodynamics and
      may prevent ischemic sequelae by optimizing existing collateral circulation.

PMID- 7822728
TI  - Acute childhood ataxia: 10-year experience.
AB  - Forty cases of acute childhood ataxia were retrospectively assessed for main
      etiologies and for factors that can be used in planning the most effective and
      cost-efficient management. The most common discharge diagnoses were acute
      cerebellar ataxia, ingestion, and Guillain-Barre syndrome, encompassing 80% of
      all cases. The remaining 20% included various isolated causes. Acute cerebellar
      ataxia was primarily seen in children less than 6 years of age who had preceding
      viral syndromes or varicella. Ingestions were also most frequent in children less
      than 6 years of age, but a second peak occurred in adolescents. History was
      suggestive of drug ingestion in 61.5% of cases, and in addition to ataxia,
      lethargy was an associated symptom. The drug screen was the most informative
      laboratory test, with 17 of 35 being positive. Lumbar punctures were positive in
      seven of 25, with pleocytosis in six and elevated protein in two. Of 26 computed
      tomographic scans and magnetic resonance imaging scans performed, only two were
      positive, one for cerebellar infarct and one for cerebral edema. Acute ataxia in
      childhood has multiple etiologies, but it is usually due to a benign, self
      limited process. A thorough history, physical examination, and drug screen should
      be performed before other costly and invasive tests and before admission to the
      hospital. This approach may eliminate the need for hospitalization of some
      patients with postinfectious acute cerebellar ataxia and ingestion. Neuroimaging
      studies should be used judiciously in the evaluation of acute ataxia, considering
      their low yield.

PMID- 7822729
TI  - Band heterotopia.

PMID- 7822730
TI  - Accessory brains (extracerebral heterotopias): unusual prenatal intracranial mass
      lesions.
AB  - Prenatal ultrasonographic evidence of intracranial mass lesions generally results
      in a diagnosis of primary glial or primitive neuroectodermal neoplasm. We
      describe two infants, one who was stillborn at 25 weeks' estimated gestational
      age and one term infant who was born live and died shortly after birth with large
      intracranial space-occupying lesions that exerted significant mass effect. At
      autopsy, large soft-tissue spheres of partially organized brain tissue containing
      neurons, astrocytes, oligodendroglia, ependyma, and choroid plexus were found
      adjacent to intact, fully formed cerebral hemispheres with normal brain stems and
      cerebelli within the cranial cavity. We have termed these extracerebral
      heterotopias "accessory brains." The telencephalic vesicles arise as lateral
      outpouchings at the rostral end of the developing embryo during the 5th week of
      embryogenesis. These accessory brains may arise embryologically from an accessory
      third evagination inferior to the telencephalic vesicles.

PMID- 7822731
TI  - Long-term MRI changes in brain after pediatric open heart surgery.
AB  - We performed magnetic resonance imaging (MRI) on the brain and neurologic
      examinations on 23 children after open heart surgery for congenital heart
      disease. Twenty children also had psychometric assessments. Examinations were
      performed at a mean age of 66 months (range, 26 to 180 months). Age at operation
      was less than 1 month in 43% and more than 6 months in 45%. Abnormal scans were
      found in 17 (74%) and showed diffuse findings consistent with hypoxic-ischemic
      encephalopathy, with or without areas of cortical infarction; focal cortical
      infarction alone; and (in one patient) callosal agenesis and abnormal neuronal
      migration. Normal IQ and neurologic examinations were found in all six of those
      who had a normal MRI, and five of six children with changes consistent with focal
      cortical infarction without diffuse change had a normal neurologic examination.
      Cerebral palsy and mental retardation was common in the group with diffuse
      abnormality (in eight of nine children), and this was more likely to occur in
      those who underwent prolonged (> 45 minutes) hypothermic circulatory arrest and
      operation during early infancy (P = .004). Focal cortical findings without
      diffuse changes were more likely in those who underwent open heart surgery
      without hypothermic circulatory arrest and were older than 6 months at operation,
      and these children were less likely to have frank neurodevelopmental sequelae.
      Thus, in our population, focal cortical lesions were common after open heart
      surgery, and, in addition, diffuse brain abnormality on MRI plus neurologic
      sequelae were common after prolonged hypothermic circulatory arrest.

PMID- 7822732
TI  - Myelinoclastic diffuse sclerosis (Schilder's disease): report of a case and
      review of the literature.
AB  - The clinical, neuroimaging, and neuropathologic features of Schilder's disease in
      a 17-year-old girl are presented and compared to 11 well-documented cases
      reported since 1912. The evolution of knowledge about Schilder's disease and the
      confusion in nomenclature are reviewed. Signs and symptoms in this case and
      others reported in the literature are nonspecific and may mimic mass lesions.
      Neuroimaging studies also may mimic brain tumor or abscess; however, the absence
      of significant edema, the irregular and incomplete ring enhancement, the
      discrepancy between size of the lesions and the associated mass effect, and the
      absence of other lesions elsewhere in the brain may help differentiate Schilder's
      disease from neoplasm, infection, and other demyelinating lesions. Although
      frozen sections of these lesions are often interpreted as astrocytoma, the
      inflammatory, primarily histiocytic, nature of Schilder's disease is more easily
      recognized in paraffin-embedded material. Unique features of this case include
      multiple unilateral lesions and the cyst-like degeneration present in both
      lesions. Multiple lesions in Schilder's disease are characteristically bilateral.
      The examination of aspirated fluid is the first such report in Schilder's
      disease. The limitation of multiple lesions in our case to one hemisphere calls
      for reexamination of the restrictive 1985 criteria of Poser for the diagnosis of
      Schilder's disease.

PMID- 7822733
TI  - Psychogenic seizures in children: long-term analysis of 43 cases.
AB  - Forty-three patients exhibiting psychogenic seizures with onset before the age of
      16 years were studied. All patients underwent intensive electroencephalography
      and video-electroencephalography monitoring. Thirty-two were female and 11 male.
      Mean age of the population at seizure onset was 12.4 years (range, 5 to 16
      years). Twenty-one patients (48.8%) were taking anticonvulsants. Neurologic past
      history was abnormal in nine cases. Family history of epilepsy was found in 15
      cases (34.9%). Median seizure frequency was one seizure every 5 days. Clinical
      characteristics of the seizures varied. However, unresponsiveness with
      generalized violent and uncoordinated movements involving the whole body (n = 19)
      or with generalized trembling (n = 11) were the most common features.
      Neuropsychological testing, carried out in 22 cases, failed to show major
      abnormalities in most of the cases. Significant personal and family distress was
      found in most of the cases. An important impact on patient's quality of life was
      evident when the seizures were present as compared to the seizure-free periods.
      There were no statistically significant predictors of clinical outcome.

PMID- 7822734
TI  - Sanfilippo type D presenting with acquired language disorder but without features
      of mucopolysaccharidosis.
AB  - A 7-year-old girl presented with a language disorder reminiscent of verbal
      auditory agnosia. Later, she proved to have defective N-acetylglucosamine-6
      sulfate sulfatase, the enzyme deficient in Sanfilippo D syndrome. She did not
      show clinical features of mucopolysaccharidosis. The language disorder had a
      fluctuating course, which eventually evolved into a progressive dementing
      encephalopathy.

PMID- 7822735
TI  - Atelencephalic aprosencephaly.
AB  - Absence of the telencephalon and diencephalon characterizes the syndrome of
      aprosencephaly, while in atelencephaly, only the telencephalon is absent.
      Atelencephalic aprosencephaly is characterized by the presence of at least a
      rudimentary diencephalon. Embryologically, aprosencephaly is thought to occur
      after the optic vesicles form but before the cerebral vesicles appear. The
      syndrome is quite rare, with only 10 cases previously reported. We describe two
      fetuses with atelencephalic aprosencephaly. A 25-week estimated gestational age
      fetus was born to first-cousin parents and had a prenatal ultrasonographic
      diagnosis of anencephaly. The second, a 19-week estimated gestational age fetus,
      was thought to have semilobar holoprosencephaly by prenatal ultrasound. At
      autopsy, neuropathologic examination in both cases showed virtual absence of the
      cerebral hemispheres with an incomplete diencephalon. Microscopic examination in
      one case revealed disorganized neuropil with a proliferative vasculopathy. The
      optic globes were completely formed and attached to hypoplastic optic nerves, but
      retinal dysplasia was apparent histologically in both cases, and bilateral
      colobomata were present in one case. The findings in these cases demonstrate a
      spectrum of congenital variations that lie between the syndromes of atelencephaly
      and aprosencephaly, underscoring the complexity of the congenital anomalies.

PMID- 7822736
TI  - Infantile spasms: an early epileptic manifestation in some patients with the
      congenital bilateral perisylvian syndrome.
AB  - We report four patients with infantile spasms and the congenital bilateral
      perisylvian syndrome. Onset of spasms occurred during the first 6 months of life.
      Response to corticotropin treatment was prompt and resulted in resolution of
      seizures in all patients. Epilepsy developed in the four children after an
      interval of 2 to 12 years. Developmental outcome was variable; three were
      severely restricted and one was married and lived independently. Imaging studies
      revealed bilateral perisylvian lesions characteristic of polymicrogyria.
      Infantile spasms may be the presenting seizure type in some patients with the
      congenital bilateral perisylvian syndrome.

PMID- 7822737
TI  - Neuropathology of Rett syndrome: case report with neuronal and mitochondrial
      abnormalities in the brain.
AB  - Neuronal changes in the brain of a Rett syndrome patient were examined in a
      frontal lobe biopsy performed at age 3 years and in the postmortem brain at age
      15 years. In the brain biopsy, frontal cortex contained numerous scattered
      pyramidal neurons with cytoplasmic vacuolation and increased cytoplasmic density,
      with no neuronophagia or inflammation detected; electron microscopy showed these
      neurons to have large, lucent-appearing mitochondria, very abundant ribosomal
      content, and some lipofuscin granules. Postmortem brain 12 years later showed
      scattered neurons in frontal cortex, substantia nigra, and cerebellar folia, with
      increased electron density of the cytoplasm, stacks of ribosomal endoplasmic
      reticulum, and large amounts of disorganized membranous material, including
      autophagic-type organelles. Mitochondria of these neurons contained electron
      dense, finely granular matrix inclusions; in the substantia nigra, some spherical
      mitochondrial inclusions completely filled the matrix space. Golgi preparations
      of (autopsy) frontal cortex and cerebellar folia showed truncation and thickening
      of dendrites and a degenerate appearance of cortical pyramidal neurons, similar
      to changes found in aged brain. Synaptophysin immunohistochemistry indicated that
      the density of synapses was not greatly altered compared to controls in frontal
      cortex and cerebellum. The patient also had a second genetic defect, severe
      combined immunodeficiency with thymic aplasia, which may be X-linked.

PMID- 7822738
TI  - The treatment of infantile spasms by child neurologists.
AB  - Infantile spasms is a refractory seizure disorder for which a number of different
      treatment regimens are available. No information is available on which treatment
      regimens are most widely used and which would be of practical importance in
      designing clinical trials to determine efficacy of new treatments. We proceeded
      to gather data on the most commonly employed methods of treating infantile
      spasms. A survey was mailed in 1991 to all junior, active, and emeritus members
      of the Child Neurology Society asking details about the treatment of infantile
      spasms. Telephone follow-up on a random sample of nonresponders was made. The
      total response rate was 58.3%. Most respondents who treat infantile spasms use
      corticotropin (ACTH) as their drug of first choice (88%). The most frequently
      used dosage was 40 IU per day, and the most frequent duration of treatment was 1
      to 2 months. The most frequently reported side effects of ACTH or oral
      corticosteroid treatment were cushingism, behavior changes or irritability,
      hypertension, topical infections, and systemic infections. Of those not using
      ACTH, valproic acid was the next most commonly employed agent, followed by oral
      corticosteroids. The results were similar for all respondents regardless of age,
      sex, type of practice, number of cases of infantile spasms seen, location (United
      States or abroad) or whether the survey was completed by mail or telephone. These
      data suggest that there is a relative uniformity among child neurologists in the
      management of infantile spasms despite the publication of many alternative
      treatment strategies.

PMID- 7822740
TI  - Are the pupils of premature infants affected by intraventricular hemorrhage?
AB  - The size and reactivity to light of the pupil in infants with intraventricular
      hemorrhage has been variously described in the literature. These descriptions
      have included miosis, reactivity to light, nonreactivity to light, and
      anisocoria. We studied the size and light reactivity of 20 infants with
      intraventricular hemorrhage compared with 30 controls. Both groups displayed a
      mean pupil diameter in relative darkness of 3.0 to 4.0 mm at various
      postconceptional ages (P > .05). The age of first response to light was about 30
      weeks after conception in each group (P > .05). The severity of intraventricular
      hemorrhage as determined by ultrasound was not related to the pupil diameter in
      relative darkness. In general, the pupils of neonates are not affected by
      intraventricular hemorrhage.

PMID- 7822739
TI  - MRI, clinical, and biochemical features of partial pyruvate carboxylase
      deficiency.
AB  - We report a boy with a partial deficiency of pyruvate carboxylase as documented
      in enzyme assays of skin fibroblasts, lymphocytes, and hepatic tissue. Magnetic
      resonance imaging at age 20 months demonstrated a leukodystrophic process
      involving the brain stem and subcortical white matter, which, except for the
      brain stem, improved after biotin treatment. The lymphocyte pyruvate carboxylase
      activity of both heterozygous parents slightly increased after receiving oral
      biotin for 1 month, but a definitive enzymatic response to biotin was not
      confirmed in our patient. At age 6 years, he is dysarthric with a spastic
      quadriparesis despite improvements in development and myelination. This is the
      first demonstration of magnetic resonance imaging changes in this disease.

PMID- 7822741
TI  - Unilateral megalencephaly and tuberous sclerosis: related disorders?

PMID- 7822742
TI  - Treatment-resistant eosinophilic polymyositis in a child.

PMID- 7822743
TI  - Handedness and spastic diplegia from premature birth.

PMID- 7822744
TI  - Intracranial plasma cell granuloma.

PMID- 7822745
TI  - Solitary mastocytoma producing symptoms mimicking those of a seizure disorder.

PMID- 7822746
TI  - Recent advances in pediatric epilepsy: 1. Experimental mechanisms and new
      diagnostic techniques.

PMID- 7822747
TI  - Inherited epilepsies of childhood.
AB  - Recent advances in neuroepidemiologic and molecular biological techniques have
      facilitated a growing understanding of the role that inherited factors play in
      epileptogenesis. During the last few years linkage analysis has mapped gene loci
      associated with the following epilepsy syndromes: benign familial neonatal
      convulsions, juvenile myoclonic epilepsy, Unverricht
      Lundborg/Baltic/Mediterranean progressive myoclonic epilepsies, the juvenile form
      of ceroid lipofuscinosis, sialidosis I, and the myoclonus epilepsy with ragged
      red fibers (MERRF) syndrome. In addition, characterization of the inheritance
      patterns of other syndromes such as childhood epilepsy with occipital paroxysms
      and febrile convulsions has improved. It is apparent that a significant amount of
      clinical and genetic heterogeneity exists, which emphasizes the importance of
      accurate clinical classification. As genetic markers are found for well-defined
      groups of patients, traditional means of classification (seizure type, pathologic
      markers, progressive course, etc.) become less meaningful. It is proposed that
      the components of the phenotype of an epilepsy syndrome (eg, age of onset,
      seizure type, electroencephalographic pattern) may be controlled by multiple
      genes.

PMID- 7822748
TI  - Developmental principles of antiepileptic drug therapy.
AB  - Antiepileptic drug therapy in children can be challenging because seizure
      semiology and drug disposition change dramatically over time. Close monitoring of
      drug clearance is required in early life because of the rapid ontogenesis of drug
      eliminating organs. Large variations in serum peak and trough antiepileptic drug
      concentrations increase the risk for both adverse drug effects and unsatisfactory
      seizure control. Antiepileptic drug adverse effects also differ, probably
      relative to different receptor sensitivities in children. Failure to appreciate
      the developmental differences between children and adults can result in
      medication noncompliance, breakthrough seizures, and unacceptable adverse
      effects.

PMID- 7822749
TI  - Testing antiepileptic drugs in children.
AB  - Few drugs have been approved by the Food and Drug Administration specifically for
      the treatment of pediatric patients with epilepsy in the United States. There are
      many factors that make tests of drugs in this group different from studies among
      adults. This report reviews issues that must be considered in designing studies
      that will help bring to market antiepileptic drugs for children. Information on
      the wide variety of antiepileptic drugs rapidly being developed can only be
      obtained through well-controlled, well-designed clinical trials. Despite the
      obstacles and pitfalls, trials among the pediatric population are necessary to
      establish the unique efficacy and safety profile of each drug and to determine
      the target, population most likely to benefit from each drug.

PMID- 7822750
TI  - Experimental models of epilepsy in young animals.
AB  - Seizures occur more frequently early in life. Some of these early seizures may
      eventually become epilepsy. Others are reactive seizures due to excessive
      environmental stimuli that, in any other age group, might not have elicited a
      similar response. To understand the developmental aspects of seizures and
      epilepsy in humans, it is important to study these processes in animals of
      equivalent ages. In this paper, we describe several animal models of
      developmental seizures, including their electroclinical manifestations and their
      validity in respect to human epileptic syndromes. There are several factors that
      may account for the increased seizure susceptibility of the immature brain,
      including the delayed development of effective systems or synaptic networks that
      are involved in the suppression of seizures. A better insight of the basic
      pathophysiology of seizures as a function of age in animal models will lead to
      the development of new therapeutic approaches for the treatment of age-specific
      epileptic disorders in humans.

PMID- 7822751
TI  - New antiepileptic drugs for children: felbamate, gabapentin, lamotrigine, and
      vigabatrin.
AB  - After a 15-year hiatus, several new antiepileptic drugs have been approved or are
      under Food and Drug Administration investigation for use in the United States.
      This article reviews four of these new drugs--felbamate, gabapentin, lamotrigine,
      and vigabatrin. Although these drugs have been primarily developed for use in
      adults with partial seizures, they will also likely be used in children with
      partial epilepsy. Pediatric experience with several of these drugs has
      demonstrated safety and efficacy in other seizure types and epilepsy syndromes.
      These drugs will be an important addition to the therapeutic armamentarium for
      pediatric epilepsy. Additional studies are needed to fully explore the safety and
      efficacy of these drugs in a variety of pediatric epilepsies and to compare them
      to existing antiepileptic drugs.

PMID- 7822752
TI  - Electroencephalographic-video monitoring in neonates, infants, and children.
AB  - Electroencephalographic (EEG)-video monitoring is a valuable tool in the
      evaluation and management of neonates, infants, and children suspected of having
      seizures or those with confirmed epilepsy. Monitoring may provide the basis for
      detection, characterization, and quantification of seizures in each of these age
      groups. The basic functional components of monitoring include: EEG, polygraphic
      measures, video, and synchronization devices that assure that all recorded
      modalities can be precisely correlated in time. Monitoring techniques may vary
      depending on patient age, clinical condition, and clinical questions to be
      addressed. Specially designed instrumentation is required to perform monitoring;
      however, the role of the technologist is central in conducting a study with
      maximum clinical yield in the most efficient manner. The clinical
      neurophysiologist must recognize the specific objectives of each monitoring study
      and appreciate the age-dependent features of the EEG and the types of clinical
      paroxysmal events that may occur at different ages. Neonates, infants, and older
      children all demonstrate special features to be considered in the conduct and
      analysis of EEG-video monitoring.

PMID- 7822753
TI  - Long-term EEG monitoring for difficult seizure problems.
AB  - Long-term electroencephalographic (EEG) monitoring, initially popular in the form
      of 24-hour video-EEG telemetries developed for the evaluation of patients who
      were candidates for epilepsy surgery, is now possible in diverse configurations.
      Studies can be designed to evaluate a variety of diagnostic problems and can be
      individualized to address specific clinical questions for each patient. A great
      variety of severe epilepsies present in infancy and childhood with daily
      seizures, often presenting difficult diagnostic problems. Extending the benefits
      of long-term EEG monitoring to these patients early in the course of the
      epileptic process can be expected to result in more accurate diagnoses, more
      effective treatment, and improved prognoses. Long-term EEG monitoring is needed
      to improve our understanding of the nosology of infant epilepsy, which is
      incomplete.

PMID- 7822754
TI  - Long-term monitoring with digital technology for epilepsy.
AB  - The use of video-electroencephalography for the evaluation of children is
      reserved for inpatients with intractable "seizures." Prolonged video
      electroencephalographic monitoring is used to ascertain whether the events are
      epileptic in nature, or to evaluate the medically intractable patient with
      epilepsy for surgical management of seizures. The increasing interest in the
      evaluation of patients with intractable epilepsy and recent technologic advances
      have led to a greater sophistication and versatility in patient evaluation. This
      paper reviews currently available technologies and newer digital acquisition and
      playback systems, and discusses ways of optimizing the evaluation of patients
      with intractable seizures.

PMID- 7822755
TI  - Functional neuroimaging with SPECT in children with partial epilepsy.
AB  - Single-photon emission computed tomography (SPECT) is being used increasingly in
      the investigation of children with intractable partial seizures. SPECT imaging of
      regional cerebral blood flow with 99mTc-hexamethylpropylene amine oxime,
      iodinated radiopharmaceuticals, and 133Xe typically reveals decreased cortical
      perfusion interictally and increased cortical perfusion ictally in the region of
      the epileptic focus. Studies in both adults and children indicate significantly
      greater sensitivity and specificity with ictal injection of radiopharmaceutical,
      with interictal SPECT not infrequently revealing nonlocalizing or falsely
      localizing information. Recent SPECT studies employing iodinated neuroreceptor
      ligands report altered receptor binding in the region of the epileptic focus,
      providing insight into the underlying neuropharmacology of partial epilepsy.
      SPECT has an established role in the presurgical localization of seizure foci in
      children with intractable partial seizures and may be a useful modality to study
      the functional anatomy and clinical semiology of partial seizures in childhood.

PMID- 7822756
TI  - The role of PET in childhood epilepsy.
AB  - Functional brain imaging with positron emission tomography (PET) has led to
      significant advances in the diagnosis and management of various forms of
      childhood epilepsy. Interictal PET in temporal lobe epilepsy typically shows
      decreased glucose utilization (hypometabolism) in one or both temporal lobes.
      Children with early-onset refractory extratemporal lobe epilepsy who do not
      manifest structural abnormalities on magnetic resonance imaging often show single
      or multiple cortical foci of hypometabolism indicating underlying microdysgenesis
      that corresponds to the area of epileptogenicity. The findings of focal cortical
      metabolic lesions and metabolic activation of subcortical structures (brain stem
      and lenticular nuclei) in patients with infantile spasms have allowed many
      infants with intractable spasms to be treated surgically with cortical resection,
      and have altered our concepts regarding the pathophysiology of these seizures.
      New observations in Lennox-Gastaut syndrome, Sturge-Weber syndrome, tuberous
      sclerosis, hemimegalencephaly, Landau-Kleffner syndrome, and other pediatric
      epilepsy syndromes have been documented with PET and have improved our
      understanding of these disorders. Recent PET studies of several neurotransmitter
      receptors in adult epileptic patients suggest that this approach holds great
      promise in the study of childhood epilepsy. The current guidelines indicating
      which patients with epilepsy should be referred for a PET study are outlined.

PMID- 7822757
TI  - Triple immunohistochemical staining for bromodeoxyuridine and catecholamine
      biosynthetic enzymes using microwave antigen retrieval.
AB  - A method was developed for detection of bromodeoxyuridine (BrdU) in conjunction
      with other antigens in formalin-fixed paraffin sections with microwave antigen
      retrieval. The method was applied to rat adrenal medulla to demonstrate S-phase
      nuclei in epinephrine-producing cells stained for immunoreactive
      phenylethanolamine-N-methyltransferase and in norepinephrine-producing cells
      stained for immunoreactive tyrosine hydroxylase. The quality of staining for all
      three antigens was comparable to or better than that previously obtained with
      other techniques. This method provides an efficient tool for studying turnover of
      subpopulations of adrenal chromaffin cells. It should also be widely applicable
      to other cells and tissues.

PMID- 7822758
TI  - Single-laser three-color immunolabeling of a histological section by laser
      scanning microscopy: application to senile plaque-related structures in post
      mortem human brain tissue.
AB  - We describe a method for observing three-color immunofluorescence simultaneously
      in a histological section under a confocal laser scanning microscope. In this
      study we investigated the spatial relationship of blood vessels, reactive
      microglia, and amyloid beta-protein (A beta) deposits in post-mortem brain tissue
      of patients with Alzheimer's disease. HLA-DR was employed as a marker for
      activated microglia and von Willebrand factor (vWF) as a marker for vascular
      endothelial cells. HLA-DR was labeled with R-phycoerythrin (R-PE) and vWF with
      fluorescein isothiocyanate. A beta-protein was immunostained with the tandem
      conjugate of R-PE and cyanin 5. Three images were obtained serially by scanning a
      tissue section with a 488-nm laser beam in combination with an appropriate
      emission filter for each fluorochrome. Overlaying of these three images permitted
      simultaneous observation of three distinct structures: activated microglia, blood
      vessels, and A beta deposits. This technique provides an improved way to study
      the localization of three different antigens in a single tissue section.

PMID- 7822759
TI  - Electron microscopic immunocytochemical evidence for the involvement of the
      convertases PC1 and PC2 in the processing of proinsulin in pancreatic beta-cells.
AB  - Endoproteolytic cleavage of pairs of basic amino acids is the key mechanism in
      the specific processing of precursor hormone molecules. Two endoproteases, PC1
      (or PC3) and PC2, have recently been implicated in the conversion of proinsulin.
      Using antibodies against these proteases and proinsulin, followed by protein A
      gold complex, we performed an immunocytochemical study for precise identification
      of the subcellular compartments involved in the processing of insulin. Both PC1
      and PC2 immunoreactivities followed a pattern of gradually increasing density
      along the secretory pathway, being higher in the immature granules. Proinsulin
      labeling was detected in the Golgi apparatus and in the coated immature secretory
      granules located mainly in the Golgi area. Using double labeling, we demonstrated
      the presence of PC1 and/or PC2 in the majority of proinsulin-rich granules. In
      addition, we provided evidence that PC1 and PC2 are co-localized within the same
      granules. Co-expression of PC1 and PC2 with proinsulin in islet beta-cells
      indicates that these proteases are actively involved, probably in a sequential
      manner, in the conversion of proinsulin into insulin.

PMID- 7822760
TI  - Ultrastructural study of proliferating cells with an improved immunocytochemical
      detection of DNA-incorporated bromodeoxyuridine.
AB  - We designed an improved method to observe proliferating cells with well-preserved
      ultrastructure. After IP injection of bromodeoxyuridine (BrdU) into rats, the
      pituitaries were fixed in 4% paraformaldehyde with 0.05% or 0.2% glutaraldehyde
      and post-fixed with ferrocyanide-reduced osmium. They were embedded in LR White
      and polymerized by heat. BrdU incorporated into DNA was detected with a
      commercial anti-BrdU monoclonal antibody (MAb) by the immunogold or the
      immunogold-silver staining method. Using these methods, proliferating cells
      labeled by BrdU were observed with well-preserved ultrastructure. By light
      microscopy, the number of labeled cells was almost the same regardless of the
      fixative used. By electron microscopy, localization of gold particles that
      indicate incorporated BrdU varied according to the cells and was mainly observed
      in two patterns, one in which gold particles were localized in condensed
      chromatin scattered in the nucleus and the other in which gold particles were
      dispersed evenly all over the nucleus. These results showed that with our
      improved method fine ultrastructure and good immunoreactivity of BrdU can be
      obtained in proliferating cells. We consider that this method is very useful for
      ultrastructural study of cell proliferation and differentiation.

PMID- 7822761
TI  - The SA/rABC technique: a new ABC procedure for detection of antigens at increased
      sensitivity.
AB  - Since its introduction, the avidin-biotin-peroxidase (ABC) complex has become an
      invaluable detection system for a wide variety of bioanalytical applications. In
      these techniques, avidin and biotin-peroxidase are mixed at a pre-determined
      ratio so that the soluble ABC complex retains biotin binding sites. Consequently,
      the complex contains an excess of avidin over biotinylated peroxidase residues.
      On theoretical considerations, however, an ABC complex designed for maximal
      signal intensity must consist of an excess of peroxidase over avidin molecules.
      Therefore, ABC complexes with reversed molar ratios of biotinylated peroxidase to
      avidin (rABC complexes) were prepared and an intermediate streptavidin step was
      introduced to bind the rABC complexes to biotinylated IgG molecules. The signal
      generating power of this new streptavidin-rABC sequence proved superior to that
      of the conventional ABC technique in ELISA assays and in immunostaining of tissue
      sections.

PMID- 7822762
TI  - Simultaneous immunoenzymatic staining of catecholamines, catecholamine
      biosynthesizing enzymes, and bromodeoxyuridine in adrenal medullary cells of the
      rat.
AB  - The rat adrenal medulla consists mainly of low proliferating, highly
      differentiated parenchymal cells. By immunocytochemical techniques, two types of
      parenchymal cells can be identified, norepinephrine (NE)- and epinephrine (E)
      storing cells. Bromodeoxyuridine (BrdU), a thymidine analogue often used to
      identify proliferating cells, can also be detected by immunocytochemical
      techniques. We developed double- and triple-labeling procedure(s) for
      simultaneous visualization of NE, E, dopamine beta-hydroxylase (DBH),
      phenylethanolamine-N methyltransferase (PNMT), and BrdU in rat adrenal medulla.
      BrdU was administered to 7-week-old Wistar rats by mini-osmotic pumps. Tissues
      were fixed by perfusion with 4% paraformaldehyde and embedded in paraffin. By
      immunocytochemistry, first NE, E, DBH, and/or PNMT was detected by an indirect
      immunoalkaline phosphatase technique with Fast Red or Fast Blue as substrate.
      Next, incorporation of BrdU was detected with an indirect immunoperoxidase
      procedure using diaminobenzidine (DAB). Both NE- and E-storing cells, as well as
      endothelial cells, can incorporate BrdU, i.e., are able to divide. Occasionally,
      we also found BrdU-stained mitotic figures in E, PNMT and DBH immunoreactive
      cells. No BrdU incorporation was found in the post-ganglionic neurons of the
      adrenal medulla. The procedures described enable a detailed cell kinetic study of
      the NE- and E-storing cells in the adrenal medulla, particularly in the rat,
      which can lead to a better understanding of cell renewal in the adrenal medullary
      tissue under normal and pathological conditions.

PMID- 7822763
TI  - Expression of MxA protein in inflammatory dermatoses.
AB  - The human MxA protein can be detected in the cytoplasm of IFN-alpha/beta-treated
      cells, whereas other cytokines, including IFN-gamma, are poor inducers. Because
      IFN-alpha/beta is predominantly synthesized in response to viral infections, MxA
      protein should be detectable in virally infected tissue. Biopsy specimens (n =
      64) of 12 different dermatoses were therefore screened with an MxA-specific
      monoclonal antibody on formalin-fixed, paraffin-embedded and microwave-treated
      tissue sections. As expected, high amounts of MxA protein were found in acute
      viral skin lesions (chickenpox, Herpes zoster, and Herpes labialis). In addition,
      MxA protein was also detected in some inflammatory skin lesions of unknown
      etiology (lupus erythematosus, lichen planus, Schoenlein-Hennoch's anaphylactoid
      purpura and psoriasis). MxA protein was not found in non-viral infections
      (bacterial, mycotic, and parasitic) and was also not detectable in various other
      dermatoses (eczema, scleroderma, urticaria, granulomatous and bullous disorders).
      MxA staining proved a reliable, sensitive histochemical viral marker for
      infectious dermatoses. The positive results in non-infectious inflammatory
      dermatoses might implicate viral involvement or activation of the IFN system by
      thus far unknown mechanisms.

PMID- 7822764
TI  - In situ hybridization of parathyroid hormone-related protein in normal skin, skin
      tumors, and gynecological cancers using digoxigenin-labeled probes and antibody
      enhancement.
AB  - We describe a novel procedure for in situ hybridization that combines the use of
      digoxigenin-labeled oligonucleotide probes with an antibody enhancement step that
      can be performed on formalin-fixed, paraffin-embedded tissues. Addition of a
      second antibody enhances the visibility of parathyroid hormone-related protein
      (PTHrP) mRNA expression from barely to highly discernible and interpretable, with
      virtually no nonspecific background expression. This technique has allowed
      visualization of PTHrP mRNA in normal human skin and epithelium-derived tumors.
      PTHrP mRNA expression was confined to the basal and spinous keratinocyte layers
      of skin. There was strong hybridization in the spinous keratinocyte layer and a
      low level of hybridization in the basal layer. An extensive panel of positive and
      negative controls included poly d(T) probe to indicate total mRNA present in the
      sections. Squamous cell carcinomas and basal cell carcinomas of the skin, from
      pathology archives, were examined for the presence of PTHrP mRNA. The results
      reflected previous immunohistochemical studies, with every squamous cell
      carcinoma hybridizing strongly with the PTHrP probes. The basal cell carcinomas
      showed no expression of PTHrP mRNA, although the total mRNA signal was very
      strong. The localization of PTHrP mRNA in the tumors of the gynecological tract
      also reflected the immunohistochemical findings, with expression found in the
      squamous cell carcinomas but not in the adenocarcinomas. In situ hybridization
      with digoxigenin-labeled oligonucleotide probes and antibody enhancement has
      provided a sensitive, highly specific procedure for detection of PTHrP mRNA in
      tumors and normal tissue.

PMID- 7822765
TI  - Differential detection of rat islet and brain glutamic acid decarboxylase (GAD)
      isoforms with sequence-specific peptide antibodies.
AB  - We studied the distribution of the M(r) 65,000 and M(r) 67,000 isoforms of
      glutamic acid decarboxylase, GAD65 and GAD67, in rat islets and brain by
      immunocytochemistry. Synthetic peptides representing selected GAD65 or GAD67
      sequences were used to produce sequence-specific antibodies, allowing
      differential immunocytochemical detection of the two isoforms. GAD-specific
      reactivity of each peptide antiserum was confirmed by ELISA, immunoblotting, and
      immunoprecipitation. Immunostaining specificity was verified by displacement with
      either immunizing or irrelevant peptide. Dual immunostaining with GAD isoform
      specific antibodies and polyclonal antibodies to glucagon showed that GAD65 was
      primarily detected in rat pancreatic islet beta-cells, whereas alpha-cells had
      weak GAD65 staining. In contrast, GAD67 was detected primarily in alpha-cells. In
      rat brain, GAD65 and GAD67 were present in neuron cell bodies and processes.
      These data demonstrate that antibodies raised against the N-terminus of GAD allow
      differential immunocytochemical identification of GAD67 and GAD65. Differential
      expression of GAD isoforms within islet alpha- and beta-cells supports the role
      of GAD65 in autoimmune diabetes and stiff-man syndrome.

PMID- 7822766
TI  - Immunohistochemical localization of rK9, an enzyme of the kallikrein gene family,
      in the rat ventral prostate.
AB  - The rat kallikrein family consists of multiple closely related proteins. Most of
      these proteins have been purified from rat submandibular gland (SMG), among them
      rK9, an enzyme that has a direct vasoconstrictory effect on isolated aortic
      rings. Recently, two members of the kallikrein family, rK8 and rK9, were also
      purified from rat prostate, whereas other family members were not detected in
      this organ. In the present study, the immunohistochemical localization of rK9 was
      determined in rat prostate by the indirect immunofluorescence technique with
      polyclonal antisera against rat SMG rK9 in the first layer. The crossreactivity
      pattern of the antiserum against rat prostate tissue extract was established by
      flat-bed isoelectrofocusing and immunoblotting. The antiserum reacted with
      prostate rK9 but not with prostate rK8. Specificity of the immunofluorescent
      staining reaction was verified by staining with the primary antiserum after
      addition of purified SMG or prostate rK9, or other members of the kallikrein
      family including prostate rK8. rK9-specific immunofluorescence was detected in
      the prostate ductal structures. In the distal (acinar) segments, rK9 was found in
      the cytoplasm as granular staining in the middle third of the cell, in the
      luminal cell wall, and in the secretion within the lumen. In the intermediate
      segments, strong rK9-specific staining was observed adhering to the luminal wall
      as well as abundantly within the ductal lumen.

PMID- 7822767
TI  - Immunocytochemical observation of the 90 KD heat shock protein (HSP90): high
      expression in primordial and pre-meiotic germ cells of male and female rat
      gonads.
AB  - We used immunocytochemistry to detect the 90 KD major heat shock protein (HSP90),
      a potential regulator of gene expression, during male and female rat gonad
      development. In the Day 13.0 post-coital (dpc) fetal gonad, strong
      immunoreactivity to anti-HSP90 antibody was shown in the cytoplasm of primordial
      germ cells (PGCs). Other somatic cells in the gonad showed only faint reactivity.
      During testicular development, strong immunostaining was observed in the
      cytoplasm of embryonic germ cells and in spermatogonia and spermatocytes of the
      pre-pubertal testis. In adult testis reactivity of spermatogonia and pachytene
      spermatocytes was strong but reactivity of post-meiotic spermatogenic cells,
      i.e., secondary spermatocytes and spermatids, was extremely reduced. During
      ovarian development, immunostaining was also observed in the oogonia and the
      oocytes of pre-pubertal ovary. However, the staining of oocytes was reduced with
      the development of primordial follicles during the first week after birth. This
      study revealed that HSP90 is highly expressed in PGCs and continues to be
      expressed in both male and female pre-meiotic germ cells. The HSP90 accumulation
      may be essential for both male and female mammalian pre-meiotic germ cells.

PMID- 7822768
TI  - Use of a new fluorogenic phosphatase substrate in immunohistochemical
      applications.
AB  - We used the phosphatase substrate 2-(5'-chloro-2'-phosphoryloxyphenyl)-6- chloro
      4-[3H]-quinazolinone, with standard alkaline phosphatase-mediated
      immunohistochemical techniques, to visualize a number of antibodies that bind to
      adult zebrafish retinal tissue. This compound, known as the ELF (enzyme-labeled
      fluorescence) phosphatase substrate, produces a precipitate that fluoresces at
      approximately 500-580 nm (bright yellow-green). We show that the precipitated
      product from the ELF phosphatase substrate has a number of characteristics that
      make it superior to fluorescein-labeled secondary reagents. The staining produced
      with the ELF substrate is much more photostable than that produced by fluorescein
      labeled secondary reagents, thus allowing time to examine, focus, and photograph
      the ELF-labeled tissue under high magnification. Moreover, the ELF precipitate
      exhibits a Stokes shift of greater than 100 nm, a characteristic that has enabled
      us to overcome the problem of distinguishing signal from background in this
      autofluorescent tissue. In addition, we show that the ELF product's large Stokes
      shift makes the ELF substrate ideal for multicolor applications.

PMID- 7822770
TI  - A novel, simple, reliable, and sensitive method for multiple immunoenzyme
      staining: use of microwave oven heating to block antibody crossreactivity and
      retrieve antigens.
AB  - We report a simple and reliable method for detection of two or more antigens
      within tissue sections by indirect immunoenzyme staining using mouse monoclonal
      antibodies (MAbs). This technique involves treating sections with two 5-min
      microwave (MW) oven heatings between sequential rounds of three-layer
      immunoenzyme staining (mouse MAb, goat anti-mouse IgG, and mouse PAP or mouse
      APAAP) and color development. Discrete staining of cell surface, cytoplasmic, and
      nuclear antigens was evident within individual cells. This technique has a number
      of advantages over those currently available. First, MW treatment denatures bound
      antibody molecules, thereby completely blocking crossreactivity between
      sequential rounds of staining. This allows the use of primary (and other)
      antibodies raised in the same species and the use of a sensitive three-layer
      staining method. Second, antigen retrieval after MW treatment markedly increases
      the sensitivity of cytoplasmic and nuclear antigen detection. Third, inactivation
      of peroxidase and alkaline phosphatase enzymes present in PAP and APAAP complexes
      prevents inappropriate color development. Finally, this method can be used in
      both paraformaldehyde-fixed cryostat sections and formalin-fixed paraffin tissue
      sections. In conclusion, this is a simple, reliable, and sensitive technique that
      will be useful in many areas of diagnosis and research.

PMID- 7822769
TI  - The gene encoding vitamin K-dependent anticoagulant protein S is expressed in
      multiple rabbit organs as demonstrated by northern blotting, in situ
      hybridization, and immunohistochemistry.
AB  - Vitamin K-dependent protein S is an anticoagulant plasma protein that functions
      as a co-factor to activated protein C in the degradation of coagulation factors
      Va and VIIIa. We investigated the tissue/cellular distribution of protein S
      synthesis by Northern blotting, in situ hybridization, and immunohistochemistry.
      Northern blotting together with in situ hybridization, using specific
      oligodeoxynucleotide probes, demonstrated protein S mRNA in liver, lung, testis,
      epididymis, ovary, uterus, and brain. In the reproductive system, protein S mRNA
      was present in the cytoplasm of Leydig cells, interstitial cells of the ovary,
      epithelial cells of the epididymis, and in the endometrium, including endometrial
      mucous glandular membrane in the myometrium. Bronchial epithelial cells and
      alveolar macrophages were positive in the respiratory system. In the central
      nervous system, pyramidal neurons in the cerebral cortex and in the hippocampal
      region, and dentate fascia neurons gave strongly positive signals.
      Immunohistochemistry with monoclonal antibodies yielded a staining pattern that
      correlated well with results of in situ hybridization. In conclusion, results
      from Northern blotting, in situ hybridization, and immunohistochemistry suggested
      that rabbit protein S is expressed in several extrahepatic tissues. The presence
      of protein S transcripts in these fully differentiated cells suggests a cell type
      specific gene expression which may be related to local anticoagulation or to
      other as yet unknown protein S functions.

PMID- 7822771
TI  - Probing for the bradykinin B2 receptor in rat kidney by anti-peptide and anti
      ligand antibodies.
AB  - The kallikrein-kinin system is involved in the inflammatory process, in blood
      pressure regulation, and in renal homeostasis. The presence of kallikreins,
      kininogens, and kinins in renal tissues and fluids is well established; however,
      the occurrence and distribution of the bradykinin (B2) receptor in the kidney are
      unknown. Using chemically cross-linked conjugates of bovine serum albumin and the
      B2 agonist bradykinin or the potent B2 antagonist HOE140, followed by antibodies
      to the respective ligand and the peroxidase-anti-peroxidase system, we were able
      to detect the B2 receptor. The receptor has been found in straight portions of
      the proximal tubules, in distal straight tubules, in connecting tubules, and in
      collecting ducts of rat kidney. The staining patterns produced by the ligand
      conjugate-antiligand approach are in agreement with those obtained by
      conventional autoradiography using [125I]-Tyr0-bradykinin. Immunocytochemical
      localization of B2 receptor by antipeptide antibodies to the receptor confirmed
      these findings and demonstrated the presence of B2 receptor in the basal
      infoldings and luminal membranes of the tubule cells, and in smooth muscle cells
      of the cortical radial artery and of afferent arterioles. Co-localization of the
      B2 receptor with kallikrein and kininogens in connecting tubule cell and
      collecting duct cell layers, respectively, provides a structural basis for the
      hypothesized physiological functions of the kallikrein-kinin system in the
      kidney.

PMID- 7822772
TI  - Immunoelectron microscopic localization of mannose-terminal glucocerebrosidase in
      lysosomes of rat liver Kupffer cells.
AB  - Knowledge of the cellular distribution and subcellular localization of mannose
      terminal glucocerebrosidase after intravenous infusion is necessary for
      understanding the efficacy of targeted enzyme replacement therapy for Gaucher's
      disease. Selective uptake of mannose-terminal glucocerebrosidase by Kupffer cells
      in rat liver has been previously demonstrated biochemically. In this study we
      used immunohistochemical and immunogold labeling techniques to provide direct
      visual proof for the localization of the delivered enzyme. Light microscopy
      confirmed biochemical data identifying non-parenchymal cells as the primary
      target of the modified glucocerebrosidase. Using a primary antibody specific for
      glucocerebrosidase and a secondary gold-conjugated antibody, we used
      immunoelectron microscopy to quantify the extent and distribution of exogenous
      enzyme in various cell types in rat liver and its localization within their
      respective subcellular organelles. Thirty minutes after intravenous
      administration of mannose-terminal glucocerebrosidase, enzyme was localized
      primarily in lysosomes of Kupffer cells. Of eight intact Kupffer cells counted,
      16 of 21 lysosomes (78%) contained immunogold conjugates (average concentration
      293 gold particles/micron 2). Of 589 particles counted in these lysosomes, 485
      (82%) were localized within the lumen of the lysosome; only 104 (18%) were
      membrane-associated. Five of the 21 lysosomes counted were negative for gold. No
      gold particles were found in the mitochondria of Kupffer cells and very few
      particles (8.2/microns 2) were found over the nucleus. The density of gold
      particles was also low over the nucleus (7.2/microns 2), mitochondria
      (8.8/microns 2), and lysosomes (7.9/microns 2) of hepatocytes. No specific
      labeling was observed in erythrocytes, platelets, lymphocytes, pit cells, fat
      storing cells, or bile duct. Background labeling of control liver sections from
      rats receiving saline injection was 8.2 +/- 1.4 gold particles/microns 2. We
      conclude that mannose-terminal glucocerebrosidase is delivered to the lysosomes
      of Kupffer cells in liver and that it is distributed both within the lumen (82%)
      and over the membrane (18%) of the lysosome, with a slight preferential
      association with the membrane. These findings may provide insights into the
      design of more effective therapeutic enzyme preparations for the treatment of
      Gaucher's disease.

PMID- 7822773
TI  - Immunocytochemical distribution of the calcium-binding protein p9Ka in normal rat
      tissues: variation in the cellular location in different tissues.
AB  - The family of S-100-related proteins consists of a number of small potential
      calcium-binding proteins of unknown function. Elevated expression of one of these
      proteins, p9Ka, or of its mRNA, correlates with the metastatic potential of
      cultured mammary epithelial cells from rat or mouse. Over-expression of p9Ka by
      transfection of benign rat mammary epithelial tumor cells with the gene for p9Ka
      induces the metastatic phenotype. At present there is little information on the
      occurrence of p9Ka in normal rat tissues. A specific antiserum
      immunocytochemically detects p9Ka intracellularly in most normal adult rat
      tissues studied, including smooth muscle, brown adipose tissue, and liver. In
      other tissues, p9Ka is localized specifically to some absorptive and keratinized
      epithelia, the acid-secreting parietal cells of the stomach, the neuronal cells
      within plexuses of the autonomic nervous system, and a proportion of cells of the
      immune system in spleen, lymph nodes, bone marrow, and blood. p9Ka is found
      widely in both arteries and veins, particularly in the smooth muscle and in the
      endothelium of smaller veins. In mammary gland, the pattern of staining suggests
      that p9Ka is extracellularly located in a region surrounding the ducts.

PMID- 7822774
TI  - Immunocytochemical detection of phosphatidylinositol 4,5-bisphosphate
      localization sites within the nucleus.
AB  - Phosphatidylinositol 4,5-bisphosphate (PIP2) is a key element of signal
      transduction, being the preferential substrate of specific phospholipases that
      produce second messengers such as inositol trisphosphate (IP3) and diacylglycerol
      (DG). Because PIP2 has been cytochemically identified by monoclonal antibodies
      not only in the cytoplasmic membranes but also in the nuclear envelope and within
      the nucleus, we performed a study by immunoblotting and by confocal and electron
      microscopic immunocytochemistry to identify the nuclear sites of PIP2
      localization and to exclude any cross-reactivity of the antibody with other
      nuclear molecules. The results confirm the specificity of the immunolabeling and
      indicate that PIP2 is localized at precise intranuclear sites both in in situ and
      in isolated nuclei. They also show that a significant amount of the phospholipid
      is retained by the cytoskeleton and by the inner nuclear matrix in in situ matrix
      preparations. Moreover the sensitivity of the immunocytochemical reaction is
      capable of detecting quantitative variations of PIP2 nuclear content induced by
      agonists that modulate the signal transduction system at the nuclear level.

PMID- 7822775
TI  - Antigen retrieval immunohistochemistry under the influence of pH using monoclonal
      antibodies.
AB  - Antigen retrieval (AR) incorporating high-temperature microwave (MW) heating of
      tissue sections before immunostaining is a revolutionary technique that can
      unmask the antigens in formalin-fixed tissue sections, thus making them available
      for immunohistochemical staining. Although high temperature is believed to be the
      primary mechanism in retrieval of antigens, a variety of chemical solutions have
      been tested to define an optimal AR solution. We tested the hypothesis that pH of
      the AR solution may influence the quality of immunostaining by using seven
      different AR buffer solutions at a series of different pH values ranging from 1
      to 10. We evaluated the staining of monoclonal antibodies to cytoplasmic antigens
      (AE1, HMB45, NSE), nuclear antigens (MIB-1, PCNA, ER), and cell surface antigens
      (MT1, L26, EMA) on routinely formalin-fixed, paraffin-embedded sections under
      different pH conditions with MW heating for 10 min. The intensity of
      immunostaining was graded in a blinded fashion. The pH value of the AR buffer
      solution was carefully measured before, immediately after, and 15 min after the
      AR procedure. The influence of pH on AR immunohistochemical staining can be
      summarized into three patterns. Some antigens (L26, PCNA, AE1, EMA, and NSE)
      showed excellent retrieval throughout the pH range. Other antigens (MIB1 and ER)
      showed strong intensity of immunohistochemical staining at very low pH and at
      neutral to high pH, but a dramatic decrease in the intensity of the AR
      immunostaining at moderately acidic pH (pH 3-6). Still others (MT1 and HMB45)
      showed increasing intensity of the AR immunostaining with increasing pH, but only
      weak immunostaining at low pH. Among the seven buffer solutions at any given pH
      value, the intensity of AR immunostaining was very similar. However, Tris-HCl
      buffer tended to produce better results at higher pH, compared with other
      buffers. Although high-temperature heating is believed to be the most important
      factor for the AR technique, the pH value of the AR solution is an important co
      factor for some antigens. Optimization of the AR system should therefore include
      optimization of the pH of the AR solution. Our results indicate that AR
      immunostaining of Tris-HCl or sodium acetate buffer at pH 8-9 may be suitable for
      most antigens, although certain nuclear antigens show optimal staining at low pH.

PMID- 7822776
TI  - Regional and maturation-associated expression of endothelin 2 in rat
      gastrointestinal tract.
AB  - Endothelin 2 (ET2), also referred to as vasoactive intestinal contractor peptide,
      is a member of a family of vasoactive peptides. ET2 is a potent constrictor of
      intestinal smooth muscle, and the mRNA that encodes it has been detected in
      murine intestinal extracts. To further investigate the potential physiological
      roles of ET2, we characterized the cellular distribution of ET2 gene expression
      in adult rat gastrointestinal tract. Using an RNAse protection assay, an overall
      proximal to distal gradient of increasing ET2 gene expression was observed from
      stomach to colon. In situ hybridization studies confirmed this finding and
      demonstrated ET2 mRNA localized in lamina propria stromal cells. Moreover, ET2
      gene expression in stromal cells increased from crypt to villous tip. The results
      demonstrate that ET2 is produced by stromal cells in villi throughout the
      intestine. Increased ET2 gene expression at the villous tip is associated with
      more mature overlying epithelial cells, suggesting a possible role for this
      vasoactive peptide in intestinal epithelial differentiation or secretory
      activity.

PMID- 7822777
TI  - Developmental patterns of histamine-like immunoreactivity in the mouse.
AB  - We studied the appearance and distribution of histamine (HA) during mouse
      embryogenesis, neonatal period, and adulthood using a specific rabbit HA
      antiserum and indirect immunofluorescence. HA first appeared on the Embryonic Day
      13 (E13) in scattered mast cells in the gastrointestinal (GI) muscularis externa
      and liver. The splenic primordium contained a dense population of intensely HA
      immunoreactive (HA-ir) cells from E13 on. From E15 to the birth, HA was detected
      in many embryonic cell types. On E15, the first HA-ir epithelial endocrine cells
      appeared in the oxyntic mucosa. In addition to the HA-ir cells in GI tract and
      liver, some nerve cells in ganglia of the peripheral nervous system (PNS), some
      fibers in spinal and cranial nerves, nerve fibers in mesenterium, and nerve
      plexuses of the gastrointestinal muscularis externa were HA-ir from E15 on.
      Occasional HA-ir nerve fibers were detected within the glandular epithelium of
      the oxyntic mucosa, pancreas, and salivary glands during late embryogenesis.
      During the same period, bright fluorescence was observed in cells of the kidney
      convoluted tubules and pancreatic islet cells. From E14 on, mast cells exhibiting
      bright fluorescence were scattered throughout the connective tissue of the fetus,
      and their number increased rapidly with age. Their density was especially high in
      subcutaneous connective tissue. Embryonic epidermal cells showed faint HA
      immunoreactivity. In musculoskeletal tissues, developing bone and occasional
      striated muscle cells exhibited HA immunoreactivity. Interestingly, most cells in
      liver showed transiently weak HA immunoreactivity during embryogenesis. In adult
      mouse, HA was stored only by scattered mast cells, oxyntic epithelial cells, and
      neurons in the tuberomamillary nucleus of the brain. The other HA-containing
      embryonic cells were negative for HA in adult mouse. In conclusion, HA
      immunoreactivity is widely distributed in epithelial, neuronal, and mast cells in
      various organs during mouse embryogenesis.

PMID- 7822778
TI  - CD28 costimulation up-regulates long-term IL-2R beta expression in human T cells
      through combined transcriptional and post-transcriptional regulation.
AB  - Costimulatory molecules such as CD28 are required for induction of T cell clonal
      expansion and for prevention of T cell unresponsiveness. In combination with
      either CD3 or CD2 triggering, CD28 was shown to enhance T cell proliferation,
      cytolytic activity, production of cytokines and especially of IL-2, and
      expression of the IL-2R alpha-chain (IL-2R alpha). We and others have
      demonstrated that the costimulatory effect of CD28 on both IL-2 and IL-2R alpha
      expression results from a coordinated transcriptional activation of their genes
      and transcript stabilization. We show here that the CD28 stimulation, together
      with CD2, leads to a prolonged up-regulation of the constitutive expression of
      the IL-2R beta-chain in human peripheral T cells. As for IL-2R alpha, the
      increase in IL-2R beta gene expression seems to result from both transcriptional
      activation and transcript stabilization. In addition, IL-2 differentially
      regulates its own receptors, as only expression of IL-2R alpha, but not of IL-2R
      beta, is largely inhibited, at both the mRNA and protein levels, by blocking IL
      2R mAbs. We propose that the long lasting T cell proliferation mediated by the
      CD2 and CD28 costimulation is mainly the consequence of the high and prolonged
      expression of both the IL-2R alpha- and beta-chains.

PMID- 7822779
TI  - Inhibition of antigen-specific T cell activation by staphylococcal enterotoxins.
AB  - The staphylococcal enterotoxins SEA, SEB, SEC2, and TSST-1 bind to MHC class II
      molecules and stimulate polyclonal T cell populations on the basis of the
      expression of responsive TCR V beta domains. CL-1 is a human T cell clone that is
      specific for a peptide derived from influenza hemagglutinin (HA 307-319)
      presented in the context of HLA-DR1. CL-1 expresses the TCR V beta 13.1 domain,
      and does not respond to SEA, SEB, or TSST-1. This T cell was used to test the
      effect of nonstimulatory staphylococcal enterotoxins on a response to antigenic
      peptide. These toxins inhibit peptide-specific activation of CL-1 in a
      concentration-dependent manner. These toxins also inhibit the response of an HLA
      DR1-specific alloreactive T cell clone. This inhibition seems to be a result of
      impaired access of TCR to the MHC/peptide complex rather than negative signaling
      by toxin via class II interaction or induction of T cell anergy. SEA, but neither
      SEB nor TSST-1 impedes avidin access to a biotin group attached to the amino
      terminus of HA 307-319. SEA partially impairs access of avidin to HA peptide
      biotinylated at residue 313, but is unable to inhibit avidin access to biotin at
      residue 318. This demonstrates that SEA binds to HLA-DR molecules that have also
      bound the antigenic peptide and suggests a topology for the interaction of SEA
      with class II, whereby the toxin interferes with peptide/MHC-TCR contact.

PMID- 7822780
TI  - Morphologic and functional alterations of mucosal T cells by cholera toxin and
      its B subunit.
AB  - Despite the mucosal immunogenicity and adjuvanticity in vivo of cholera toxin
      (CT), both CT and CT B subunit are strong inhibitors of T cell activation in
      vitro. This study asked whether such T cell inhibition is relevant to the mucosal
      effects of CT in vivo. The activation of T cells pulsed in vitro for only 15 to
      120 min with CT or CT B subunit, respectively, was inhibited, consistent with the
      expected short exposure times in vivo. Although both CD8+ and CD4+ T cells were
      inhibited in vitro, CD8+ T cells bound more toxin and were inhibited to a greater
      degree than were CD4+ T cells. Intestinal gavage of mice with 10 micrograms CT
      did not alter the overall composition of Peyer's Patch, mesenteric lymph node, or
      spleen but did cause a marked depletion of intraepithelial lymphocytes, mainly
      CD8+ T cells, and of lymphocytes in the dome epithelium over Peyer's Patch. To
      determine whether such inhibition of T cells was functionally relevant in vivo, T
      cells from mice fed keyhole limpet hemocyanin (KLH) were adoptively transferred
      into naive recipients, who were then parenterally immunized. T cells from mice
      fed KLH alone inhibited both the systemic IgG and secretory IgA anti-KLH
      response, but T cells from mice fed KLH plus CT did not, indicating that
      mucosally applied CT was able to abrogate the induction of this suppressor T
      cell. We conclude that one of the mechanisms of CT's mucosal effects in vivo is
      the inhibition of certain mucosal T cell functions and alteration of the
      regulatory T cell environment in gut-associated lymphoid tissue.

PMID- 7822781
TI  - Specific suppression by prostaglandin E2 of activation-induced apoptosis of human
      CD4+CD8+ T lymphoblasts.
AB  - Receptors (Rs) for prostaglandin E2 (PGE2) of the EP2 subtype are expressed at
      high levels in rodent and human thymuses, with preferential localization on
      immature thymocytes. Human cultured lymphoblasts of the Tsup-1 line express CD4
      and CD8 but only a low level of CD3, typical of immature thymocytes, and bear EP2
      type Rs for PGE2 that were identified by binding of [3H]PGE2 and Ab to
      recombinant EP2Rs, and by cAMP responses to PGE2. PGE2 protected Tsup-1 cells
      from apoptosis initiated by diverse stimuli, including mitogenic lectins and anti
      Fas or anti-CD3 plus anti-CD28 Abs, but not ionomycin, as assessed by suppression
      of both fragmentation of [3H]thymidine-labeled DNA and appearance of free 3'-OH
      ends of cleaved DNA. An EP2R-selective synthetic agonist also significantly
      suppressed lectin-induced apoptosis of Tsup-1 cells. Phosphodiesterase inhibition
      synergistically enhanced PGE2-induced increases in cAMP and decreases in
      apoptosis in parallel, which suggests that the EP2R-specific protective effect of
      PGE2 is mediated predominantly by cAMP suppression of apoptosis. Dibutyrylcyclic
      AMP alone protected Tsup-1 cells against lectin-induced apoptosis, but the
      maximal effect was less than that for PGE2. The thromboxane A2 mimetic U46619
      initiated apoptosis of Tsup-1 cells that was suppressed significantly by PGE2.
      Immune negative selection of immature thymocytes thus may be regulated by
      opposing effects of endogenous eicosanoids that include destruction by
      thromboxane A2 and protection by PGE2.

PMID- 7822782
TI  - Acquisition of peptides by MHC class II polypeptides in the absence of the
      invariant chain.
AB  - Association of invariant chain with class II molecules has been suggested to
      inhibit binding of peptides that are available while the class II complex is
      present in the endoplasmic reticulum (ER) and subsequently transported to
      endosomes. We tested HLA-DR-transfected rat2 fibroblast cells lacking expression
      of invariant chain for their ability to form SDS stable class II dimers
      indicative of peptide binding in the class II cavity. No SDS-resistant class II
      dimers originating from short pulse-labeled immunoprecipitates can be identified.
      Prolonged ER retention of DR polypeptides by Brefeldin A treatment does not
      induce any stable class II dimers. In pulse-chase experiments, heat labile class
      II dimers are readily detectable after a 60-min chase, increasing in amounts by 4
      h of chase. In vitro incubation of rat2DR cell lysate with DR3-binding peptides
      converts pulse-labeled class II molecules to SDS-resistant dimers. This indicates
      the ability of ER-resident DR dimers to bind peptides. Inhibition studies were
      conducted to define the intracellular site where stable class II complexes are
      formed in rat2DR cells. The lysosomotropic reagent chloroquine abrogates the
      appearance of SDS-resistant DR complexes in invariant chain-free rat2DR cells,
      which is consistent with the impact of chloroquine on peptide loading in other
      APCs. Leupeptin treatment strongly reduces the amount of heat-labile class II
      molecules but does not impair peptide loading when DR3-specific peptides were
      added to viable cells or to cell lysates. This result suggests that leupeptin
      inhibits intracellular degradation of polypeptides and thereby depletes the
      endocytic pathway of peptides available for class II binding.

PMID- 7822783
TI  - Role of TCR specificity in CD4 versus CD8 lineage commitment.
AB  - We have examined the role that TCR-alpha beta specificity plays in lineage
      commitment of thymocytes. Thymocytes in the process of selection have been
      distinguished by the expression of high levels of CD69 and CD5. The phenotype of
      most of these selected thymocytes is either CD4highCD8low or CD4lowCD8high, but
      some are CD4lowCD8low, a phenotype referred to as double-positive dull. Analysis
      of the phenotype of apoptotic thymocytes shows that double-positive dull cells
      make up many of the cells undergoing negative selection. Thymocytes from MHC
      class I- or class II-deficient mice and from MHC class I- and class II-restricted
      TCR transgenic mice have been analyzed for cells undergoing positive and negative
      selection. This analysis shows that the TCR specificity is a critical factor in
      the lineage determination of thymocytes, and any stochastic component to lineage
      commitment is minor.

PMID- 7822784
TI  - Requirement of CTLA-4 counter receptors for IL-4 but not IL-10 elevations during
      a primary systemic in vivo immune response.
AB  - The CD28/CTLA-4 costimulatory signal is required for TCR-mediated T cell
      activation resulting in increased IL-2 production in vitro, but its role in IL-4
      production is unclear and few studies have examined the function of CTLA-4/CD28
      in the in vivo immune response. We have examined the in vivo effects of blocking
      the interaction of B7 with its ligands, CTLA-4 and CD28, in an IL-4 dominant in
      vivo immune response to goat anti-mouse IgD. This response is characterized by
      elevations in serum Igs preceded by elevations in IL-2 and the Th2 cytokines: IL
      4, IL-9, and IL-10. The fusion protein CTLA4-Ig administered during the in vivo
      immune response to goat anti-mouse IgD caused an inhibition in elevations of IL
      2, IL-4, and IL-9 gene expression at both day 3 and day 6 after immunization. In
      contrast, IL-10 cytokine gene expression as late as day 6 after immunization was
      not decreased. Cell sorting analysis demonstrated that TCR-alpha beta +, CD4+ T
      cells were the primary source of the elevated IL-10, suggesting that T cell
      activation leading to IL-10 gene expression may not require CTLA-4 ligand
      interactions. Similarly CTLA4-Ig completely blocked elevations in the number of
      IL-4- but not IL-10-secreting cells, as measured by ELISPOT, in both unsorted
      splenic cells and sorted CD4+, TCR-alpha beta+ T cells. In situ staining of
      spleen sections also showed inhibition of IL-4-producing cells. These results
      suggest that, with the notable exception of IL-10, interaction, of B7 with its
      ligands is required for elevated Th2 cytokine gene expression and secretion
      during a primary systemic IL-4-dominant response.

PMID- 7822785
TI  - Genetic evidence for difference between intracellular and extracellular peptides
      in influenza A matrix peptide-specific CTL recognition.
AB  - During the course of extensive mutagenesis of HLA-A2.1, we examined influenza A
      matrix peptide (FMP)-specific CTL recognition of HMy2.C1R (C1R) cells expressing
      mutant HLA-A2.1 molecules, sensitized with synthetic peptide, FMP 58-66,
      (exogenous peptide), or infected with influenza A virus (endogenous peptide).
      Most mutants showed equivalent presentation of exogenous and endogenous peptides
      to FMP-specific CTL. However, five of the mutants differed in this property. Two
      of the five mutants, F9L and T134K, present exogenous peptide to FMP-specific
      CTL, but fail to present endogenous peptide to CTL. Western blot analysis using
      anti-matrix protein Ab indicates that the matrix protein is expressed in these
      mutants after infection with virus. Interestingly, transfection of these two
      mutants with a minigene encoding FMP 58-66 results in efficient lysis by FMP
      specific CTL. Peptide-binding assays demonstrate that the two mutations
      dramatically decrease the binding of FMP. However, these mutants bind FMP as well
      as wild type in the presence of exogenously added human beta 2-m, suggesting that
      the lower affinity for beta 2-m leads to the inability to present endogenous
      peptide. The remaining three mutants, Y27N, Q32K, and S132C, fail to present
      exogenous peptide, but present endogenous peptide to FMP-specific CTL. Pulse
      chase analyses followed by endoglycosidase-H treatment show that the rate of
      maturation and processing of the five mutant HLA-A2 molecules in C1R cells is
      identical to that of wild type. Overall, this study suggests that the assembly
      and subsequent recognition of endogenous peptide differs from that of exogenous
      peptide.

PMID- 7822786
TI  - CD43 diminishes susceptibility to T lymphocyte-mediated cytolysis.
AB  - CD43 is a major membrane sialoglycoprotein expressed by cells of hematopoietic
      origin. One property of CD43 is its ability to interfere with heterotypic and
      homotypic cellular adhesion. To determine whether CD43 expression can affect cell
      functions requiring intercellular adhesion, we compared a CD43-positive human T
      cell line (CEM) and its CD43-negative counterpart derived by gene targeting for
      susceptibility to cell-mediated lysis. CD43-negative CEM cells were more
      susceptible than CD43-positive cells to lysis by allospecific T cell lines
      derived from several donors. Induction of CD43 expression on transfected HeLa
      cells also imparted resistance to lectin-mediated lysis by a CD8+ T cell clone.
      The effect of CD43 expression on reducing susceptibility to lysis was more
      pronounced in short-term cytotoxicity assays and tended to disappear as the time
      of contact between the effector cell and its target increased. The enhanced
      susceptibility of CD43-negative cells to lysis was not associated with increased
      expression of adhesion molecules known to mediate antigen-independent cellular
      adhesion. Sialic acid residues on CD43 contributed to the CD43 protective effect.
      These results suggest that either diminished CD43 expression or incomplete
      sialylation may render hematopoietic cells more susceptible to T lymphocyte
      mediated cytolysis.

PMID- 7822787
TI  - Memory B lymphocytes in human tonsil do not express surface IgD.
AB  - To clarify the phenotype of memory B lymphocytes, we have determined the
      frequency of somatic hypermutations in purified tonsil B cell populations. Our
      particular interest was the controversial question of whether any memory B-cells
      express IgD. Ig heavy chain gene rearrangements that used the nonpolymorphic VH6
      gene were amplified by PCR, cloned, and sequenced. All eight sequences obtained
      from the surface IgD (sIgD)-negative fraction contained point mutations, with
      frequency of one mutation in every 24 bases of sequence. In contrast, only 4 of
      12 sequences obtained from the sIgD-positive fraction contained point mutations,
      with a mutation frequency of one in 600. This frequency was similar to that found
      for cord blood B cells (one in 550), a population that does not contain memory B
      cells. These results indicate that although memory B cells are present in the
      sIgD-negative fraction, no memory cells can be detected in the sIgD-positive
      fraction of tonsil B lymphocytes.

PMID- 7822788
TI  - Induction of murine gamma delta T cells cytotoxic for xenogeneic rat cells.
AB  - C57BL/6 mice deprived or nondeprived of CD4+ and CD8+ T cells by mAbs were
      challenged with a rat T cell line, W7TM-1. Spleen cells obtained from CD4- and
      CD8-depleted animals rejecting W7TM-1 were examined by cytofluorometry, which
      demonstrated the presence of highly increased gamma delta type CD4-CD8- T cell
      population (30 to 50% of entire T cells). In vitro sensitization of these spleen
      cells with W7TM-1 generated a mixture of gamma delta and alpha beta type CD4-CD8-
      CTL for W7TM-1. Repeated stimulation of these cells with W7TM-1 resulted in a
      gamma delta-type T cell population with more than 95% purity by day 45. In
      contrast, alpha beta type CD8+ CTL for W7TM-1 were induced from mice nondeprived
      of CD4+ and CD8+ T cells. Both gamma delta-type CD4-CD8- CTL and alpha beta type
      CD8+ CTL were cytotoxic for rat cells in a species-specific manner. However, only
      reactivity of gamma delta type CD4-CD8- CTL, but not alpha beta type CTL, was
      inhibited by a mAb for TCR-gamma delta. The gamma delta type CD4-CD8- CTL clones
      were also prepared from spleen cells derived from CD4- and CD8-depleted mice.
      They were also reactive for xenogeneic cells in a species-specific manner. Spleen
      cells derived from CD4- and CD8-depleted mice rejecting the whole-layer rat skin
      grafts were in vitro sensitized with rat spleen cells, which also generated gamma
      delta type CD4-CD8- CTL specific for rat cells. V gamma 1 was detected as a major
      V gamma gene expressed in this gamma delta population by reverse transcriptase
      PCR. Cytotoxicity for xenogeneic cells may represent one of major function of
      gamma delta T cells.

PMID- 7822789
TI  - Human p59fyn(T) regulates OKT3-induced calcium influx by a mechanism distinct
      from PIP2 hydrolysis in Jurkat T cells.
AB  - The earliest biochemical event after cross-linking of TCR is the tyrosine
      phosphorylation of a variety of substrates. At least three nonreceptor tyrosine
      kinases have been implicated in this signaling cascade: p59fyn(T), p56lck, and
      ZAP-70. Recently, PLC gamma 1 has been shown to be tyrosine phosphorylated in T
      cells after receptor activation. This increase in tyrosine phosphorylation
      correlates with the increased activity of the enzyme. The substrate for PLC gamma
      1, phosphatidylinositol 4,5-bisphosphate (PIP2), is hydrolyzed to the protein
      kinase C activator diacylglycerol and inositol 1,4,5-triphosphate (IP3), which
      promotes calcium release from the endoplasmic reticulum. These results lend
      support to the notion that calcium mobilization after TCR cross-linking is
      mediated by increased levels of IP3. In this study we have cloned and transfected
      a human p59fyn(T) cDNA in the anti-sense configuration into the human T cell
      line, Jurkat, resulting in decreased expression of the protein. We find that cell
      lines expressing significantly reduced levels of p59fyn(T) exhibit significantly
      lower calcium influx following OKT3 activation. However, the level of IP3
      production was unchanged and IP1 and IP2 levels were elevated. These data
      indicate that p59fyn(T) can regulate calcium influx by a mechanism distinct from
      PIP2 hydrolysis.

PMID- 7822790
TI  - Protein kinase C activation inhibits TCR-mediated calcium influx but not inositol
      trisphosphate production in HPB-ALL T cells.
AB  - The regulation by protein kinase C (PKC) of TCR-mediated changes in
      phosphoinositide metabolism and intracellular calcium ([Ca2+]i) was investigated
      in HPB-ALL T cells. Low concentrations (< 1 microgram/ml) of the anti-CD3 OKT3
      mAb triggered large calcium signals but not detectable increase in D-myo-inositol
      1,4,5-trisophate (IP3) production. CD3-CD4 coligation amplified the calcium
      signal twofold, compared with CD3 cross-linking alone, but this protocol also did
      not stimulate IP3 production. At higher OKT3 concentrations (> 2.5
      micrograms/ml), IP3 production was detected but was not inhibited by activating
      PKC with phorbol ester. In contrast, PKC activation caused a marked inhibition
      (53 to 64%) of the CD3- or CD3-CD4-triggered calcium signals, but had only a
      small inhibitory effect (20 to 30%) on the release of intracellular Ca2+. PKC
      activation also inhibited by 47% calcium signals triggered by thapsigargin, an
      inhibition that was completely reversed by addition of the specific PKC inhibitor
      RO 31-8220 (1 microM). Addition of 1 microM RO 31-8220 caused a twofold
      stimulation of CD3-induced calcium signals. This effect was not mediated at the
      level of Ca2+ influx, because RO 31-8220 did not significantly increase
      thapsigargin-triggered calcium signals. However, RO 31-8220 did slightly increase
      the CD3-induced release of intracellular Ca2+, suggesting that amplification of
      Ca2+ influx may be secondary to increased release of Ca2+ from intracellular
      stores. Our results indicate that PKC regulates TCR-mediated changes in [Ca2+]i
      in HPB-ALL T cells by two distinct mechanisms. First, PKC activation causes a
      marked inhibition of Ca2+ influx by a mechanism independent of changes in IP3
      production, possibly involving inhibition of ion channels. Second, PKC activity
      causes a small inhibition of intracellular Ca2+ release, most likely by promoting
      Ca2+ sequestration.

PMID- 7822791
TI  - The receptor tyrosine kinase-related gene (ryk) demonstrates lineage and stage
      specific expression in hematopoietic cells.
AB  - We attempted to isolate novel receptor tyrosine kinase, which may play a role in
      hematopoietic development by screening for expressed sequences with conserved
      tyrosine kinase catalytic domains. Among the known tyrosine kinases identified in
      this screen, we found a gene with characteristics of a receptor tyrosine kinase
      but unusual motifs in the catalytic domain. This gene is identical to ryk
      described independently by other investigators. Chromosomal fluorescence in situ
      hybridization localization of human ryk was clarified by using monochromosomal
      hybrids and placing it as a single locus in 3q22. Although Northern analysis
      reveals widespread expression in adult mouse tissues, we have found that ryk
      expression is not ubiquitous. Expression increased in bone marrow cells from mice
      treated with 5-fluorouracil. Northern analysis on cell lines indicates expression
      in CD3-, CD4-, CD8- T cells (at a low level), pre-T cells, thymic epithelial
      cells, and mature myeloid cells, but not myeloid precursors or B cell precursors.
      Expression analysis with the use of RT-PCR on mouse bone marrow cells separated
      on the basis of cell surface markers (B220, CD4, CD8, Gr-1, Mac-1) reveals that
      this receptor is expressed in differentiated cells (Lin+) but is not expressed in
      the precursor cells (Lin-). Flow cytometric analysis with a monospecific anti-Ryk
      Ab demonstrates that Ryk+ cells constitute 36.7% and Lin+/Ryk+ cells constitute
      33.7% of low density bone marrow cells whereas Ryk+ cells represent only 0.3% of
      the Lin- population. We conclude that ryk expression is regulated during
      hematopoietic development by lineage commitment and stage of maturation.

PMID- 7822792
TI  - Split tolerance in spleen chimeras.
AB  - Transferring small doses of T cells to heavily irradiated F1 mice expressing
      isolated MHC class I or class II differences invariably leads to rapid death from
      graft-vs-host disease (GVHD). Paradoxically, GVHD is mild or absent when
      irradiated F1 mice are reconstituted with large doses of unseparated parental
      strain spleen cells. This applies when bulk populations of B6 spleen cells are
      transferred to irradiated class II-different (B6 x bm12)F1 mice or class I
      different (B6 x bm1)F1 mice. In this study, we examined whether the donor T cells
      in long-term spleen chimeras become tolerant to host MHC Ags. On the basis of
      skin-allograft rejection and induction of GVHD on adoptive transfer, the results
      show that the donor T cells display strong tolerance to host antigens; this
      applies to CD4+ cells in class II-different chimeras and to CD8+ cells in class I
      different chimeras. In marked contrast to the profound tolerance seen by these in
      vivo parameters, little or no tolerance is observed in standard in vitro assays.
      The results illustrate that typical in vitro tests for alloreactivity are an
      imprecise guide to physiologic tolerance of T cells in vivo.

PMID- 7822793
TI  - Analysis of homology-directed recombination in VDJ junctions from cytoplasmic Ig-
      pre-B cells of newborn mice.
AB  - We previously showed that most VD and DJ gene combinations from newborn surface
      Ig- pre-B cells had one to three predominant junctions, all of which occurred at
      the sites of short sequence homologies between the two coding ends. Because the
      majority of sequences that are present in pre-B cells are in-frame, however, the
      possibility existed that the frequency of occurrence of predominant IgH junctions
      was skewed by proliferation of pre-B cells with productive rearrangements. In
      this study, we analyzed cytoplasmic Ig- pre-B cells, because these cells should
      not yet be subject to such selection. Two-thirds of the rearrangements from this
      population in the adult were out-of-frame, suggesting that these rearrangements
      are unbiased. In newborn cIg- pre-B cells, DJ junctions still showed the same
      predominant sequences as sIg- pre-B cells, but there was less use of predominant
      junctions in VD junctions for three of four different VH genes analyzed. For
      those three VH genes, an average of 30% of the sequences were in-frame. When only
      the in-frame rearrangements from these cIg- newborn cells were analyzed,
      frequencies of predominant VD junctions were comparable to those in sIg- pre-B
      cells. For sequences using the VHS107/V11 gene, however, 67% of the junctions
      were created at the site of the same dinucleotide in the V gene, and as a result,
      73% of the sequences were in-frame. Thus homology-directed recombination does not
      initially produce as much junctional homogeneity as anticipated in all VD
      combinations, although it is a frequently used mechanism in the early
      fetal/neonatal gene rearrangements.

PMID- 7822794
TI  - Ontogeny of TCR V beta 1 expression revealed novel invariant alternative
      transcripts.
AB  - Analysis of TCR-beta gene recombination and expression was performed by
      quantitative PCR amplification technique throughout chicken embryogenesis and
      development. Our data demonstrated that TCR V beta 1 promoters were turned on by
      day 10 of embryogenesis, 2 days before detection of TCR-beta gene recombination.
      The V to D recombination step was first detected by day 11 of embryogenesis
      whereas DJ and V(D)J rearranged genes were detected 1 day later, on day 12 of
      embryogenesis. Thus, transcription of unrearranged TCR-beta genes in chickens
      precedes the expression of V(D)J recombinase activity as in mammals. In contrast,
      although TCR-beta rearrangement starts with the D to J recombination step in
      mammals, it can start either by the VD or the DJ step in chickens. Furthermore,
      reverse transcriptase-PCR amplification of TCR-beta transcripts revealed the
      presence of two kinds of alternative transcripts. These novel alternatively
      spliced products appeared in thymocytes from embryonic thymus during colonization
      periods and were absent in transformed T cell lines. Splicing sites are located
      in the middle of V beta 1 segments and lead to delta V beta 1-C beta and delta V
      beta 1-D beta-J beta-C beta transcripts. delta V beta 1-C beta transcripts might
      lead to synthesis of invariant truncated TCR beta-chains containing the
      aminoterminal portion of the V beta 1 region followed by the C beta region.
      Because this type of splicing can be generated by using all known V beta 1
      members, these invariant forms could play a role in thymocyte development.

PMID- 7822795
TI  - Molecular cloning, characterization, and chromosomal localization of a human
      lymphoid tyrosine kinase related to murine Blk.
AB  - Triggering of Ag receptors on lymphocytes induces rapid phosphorylation of
      several receptor-associated protein tyrosine kinases (PTKs), implicating their
      role in controlling cellular growth and differentiation. In this study, we report
      the cloning of a human cDNA encoding a nonreceptor PTK with a calculated M(r) of
      about 58 kDa. The kinase has an overall amino acid identity of approximately 87%
      with the murine Blk. However, in the unique domain there is only 58% homology and
      an insertion of six amino acids in the N-terminal region. The nature of this
      insertion suggests a functional role in membrane attachment. Northern blot
      analysis showed expression in all stages of B cell development and in T cell
      lines. The message was not observed in the nonlymphoid tissues examined. In
      contrast, expression of murine blk in plasma cells and T lymphocytes has not been
      reported. Importantly, transcripts were seen in human embryonic liver as early as
      7.5 wk of gestation before the rearrangement of Ig H chain locus. Furthermore,
      transcripts were detected in human thymocytes and not in mature T cells. Southern
      blot analysis revealed polymorphism of this gene in a Caucasian population but
      not in a Gambian population, indicating a recent origin of this polymorphism. The
      gene was localized to chromosome 8p22-23. The homology at the protein level
      suggests that this kinase may be the human homologue of murine Blk. Expression of
      BLK in immature T cells suggests that BLK may play an important role in
      thymopoiesis.

PMID- 7822796
TI  - Major differences in transporter associated with antigen presentation (TAP)
      dependent translocation of MHC class I-presentable peptides and the effect of
      flanking sequences.
AB  - The MHC-encoded transporter associated with Ag presentation (TAP) translocates
      peptides from the cytosol to the ER lumen, where association with MHC class I
      molecules occurs. The MHC class I/peptide complex is subsequently transported to
      the cell surface for presentation to CD8+T cells. We studied TAP-dependent
      translocation of defined MHC class I presentable murine peptides by competition
      for translocation of a radiolabeled model peptide, to address whether efficient
      peptide presentation by MHC class I molecules is preceded by equal efficient
      peptide translocation by TAP. Surprisingly, we observed that four immunodominant
      viral peptides of 16 peptides tested were very inefficiently transported by TAP.
      Inefficient translocation could be overcome by substitution of a proline residue
      present at position 3 in the peptides. Furthermore, addition of natural flanking
      amino acids directly surrounding a poorly transported peptide could considerably
      improve translocation by TAP. Our data suggest that some peptides are efficiently
      transported by TAP in their optimal size for MHC class I binding, whereas other
      peptides are transported as larger peptide fragments that need further trimming
      in the ER for MHC class I binding.

PMID- 7822797
TI  - IL-10 inhibits tumor antigen presentation by epidermal antigen-presenting cells.
AB  - IL-10 inhibits Langerhans cell (LC) Ag presentation to Th1 clones. As LC are
      capable of presenting tumor-associated Ags (TAA) for primary and secondary tumor
      immune responses, we examined the effect of IL-10 on LC Ag presentation in a
      model of immunity to the S1509a spindle cell tumor (H-2a). Because induction of
      immunity to S1509a requires exposure of LC to granulocyte-macrophage (GM)-CSF,
      this system also allowed us to study the regulatory interactions of GM-CSF and IL
      10 on LC. Naive CAF1 (H-2a/d) mice could be immunized against S1509a by injection
      with GM-CSF-exposed and TAA-pulsed epidermal cells (EC) as assessed by inhibition
      of the growth of inoculated tumor cells. Incubation of EC in IL-10 before GM-CSF
      exposure completely inhibited Ag presentation in this system. Significantly,
      neither co-incubation of EC in IL-10 and GM-CSF (without preincubation in IL-10)
      nor IL-10 treatment after GM-CSF incubation was able to exert a down-regulatory
      effect. The ability of IL-10 to modulate EC presentation of TAA for a secondary
      immune response was also examined. EC were pulsed with TAA in vitro and then
      injected into a hind footpad of tumor-immune mice with 24 h swelling assessed as
      a measure of delayed-type hypersensitivity. Preincubation in IL-10 before TAA
      exposure significantly inhibited elicitation of delayed-type hypersensitivity
      with or without subsequent exposure to GM-CSF. Co-incubation of EC in IL-10 and
      GM-CSF or exposure to IL-10 after GM-CSF led to a normal response. These data
      indicate that IL-10 may serve as an important regulator of LC Ag-presenting
      function for tumor immune responses. IL-10 appears to specifically prevent the GM
      CSF-induced maturation of LC Ag-presenting function when treatment with IL-10
      occurs before exposure to GM-CSF but does not reverse the established mature
      state.

PMID- 7822798
TI  - Docosahexaenoic acid, a major constituent of fetal serum and fish oil diets,
      inhibits IFN gamma-induced Ia-expression by murine macrophages in vitro.
AB  - Decreased Ia expression by macrophages may account for the increased
      susceptibility of fetuses and neonates to infection. We chose to investigate the
      role of docosahexaenoic acid (DHA), an omega-3 fatty acid, on Ia expression in
      vitro, because neonatal serum concentrations of DHA (100-150 microM) are
      approximately 50 times higher than in the adult. In addition, DHA is a major
      component of fish-oil diets that ameliorate some autoimmune diseases and prevent
      renal allograft rejection. DHA inhibited IFN-gamma-induced Ia expression with a
      half-maximal inhibitory concentration of 25 microM. The inhibition was not caused
      by nonspecific damage, because oxidative metabolism via the mitochondrial
      electron-transport chain was not inhibited. There were strict biochemical
      requirements for inhibition of Ia expression. Polyenoic fatty acids with 22
      carbons were more inhibitory than those with 20 carbons. Among 22-carbon fatty
      acids, those with more double bonds, and, in particular, with a double bond in
      the omega-3 position, were more inhibitory. Although DHA is known to inhibit
      cyclooxygenase and thus the production of eicosanoids, indomethacin did not
      inhibit Ia expression. This indicated that inhibition of cyclooxygenase was not
      responsible for inhibition of Ia expression. We divided induction of Ia
      expression by IFN-gamma into four phases, with IFN-gamma being present only
      during the second phase. DHA was most inhibitory when given before or with the
      IFN-gamma. This indicated that DHA inhibited early steps in IFN-gamma-induced Ia
      expression. Consistent with this idea, we found that DHA inhibited the increase
      in mRNA transcripts for Ia beta b, as assayed by Northern blotting. In summary,
      we found that DHA, a major component of fetal and neonatal sera as well as fish
      oil diets, inhibited IFN-gamma-induced macrophage Ia expression in vitro by
      preventing increases in Ia mRNA transcripts.

PMID- 7822799
TI  - Activation of the 55 kDa TNF receptor is necessary and sufficient for TNF-induced
      liver failure, hepatocyte apoptosis, and nitrite release.
AB  - The systemic inflammatory response is characterized by release of circulating TNF
      which may cause multiorgan failure including septic liver failure. We studied TNF
      signaling in an appropriate in vitro system with primary murine hepatocyte
      cultures from normal and genetically altered animals. Either one of the three
      different TNF species, huTNF-alpha, huTNF-beta, or muTNF-alpha (at concentrations
      > 1 ng/ml) induced direct hepatocytotoxicity preceded by DNA fragmentation in
      cells prepared from wild-type C57BL mice. TNF-induced cytotoxicity was preceded
      by oligonucleosomal DNA fragmentation. Further cellular responses to TNF exposure
      were induction of nitric oxide synthase and secretion of serum amyloid A. None of
      the above events occurred in hepatocytes lacking the gene for the 55-kDa TNF
      receptor (TNF-R1), even after stimulation with > 1 micrograms/ml TNF. However,
      selective stimulation of the TNF-R1 in wild-type hepatocytes with huTNF-alpha
      elicited a pattern of responses essentially similar to that seen with muTNF
      alpha. We obtained analogous results when we examined the hepatotoxicity of TNF
      in D-galactosamine-sensitized mice, i.e., DNA fragmentation and liver failure was
      noted in wild-type mice, whereas TNF-R1-deficient mice were completely resistant.
      We conclude that the TNF-R1 is not only necessary, but also sufficient for TNF
      signaling in murine hepatocytes.

PMID- 7822800
TI  - Endotoxin-mediated dendritic cell release from the intestine. Characterization of
      released dendritic cells and TNF dependence.
AB  - Dendritic cells (DC) acquire Ag in peripheral tissues and transport it to lymph
      nodes where they efficiently activate resting T cells. We have shown that i.v.
      endotoxin causes increased release of intestinal DC into lymph. In this paper we
      further characterize the release of DC and the properties of the released cells.
      A total of 50 micrograms of endotoxin injected i.v. causes an increase in DC
      output within 6 h that peaks between 12 and 24 h, with a maximum output of 8 to
      15 times normal. At the same time lymphocyte output is markedly decreased. The
      increased output of DC is followed by a decrease to subnormal levels. The
      stimulated release of DC is almost totally blocked by a monoclonal anti-TNF-alpha
      Ab. A second injection of TNF-alpha does not result in further DC release. DC are
      not released from lymph nodes into efferent lymph by endotoxin. DC collected from
      lymph after endotoxin treatment show increased expression of the p55 IL-2
      receptor and the OX48 Ag but otherwise resemble normal lymph DC. In functional
      assays they show no significant differences from normal in their ability to
      stimulate a MLR or to present Ags to sensitized T cells. Immunocytochemistry with
      the use of MRC OX62 suggests that the DC are released into lymph from the lamina
      propria of the small intestine. The stimulated release of DC mediated by TNF
      alpha may be important in regulating Ag presentation in lymph nodes draining
      inflammatory sites.

PMID- 7822801
TI  - Human granulocytes contain an opiate alkaloid-selective receptor mediating
      inhibition of cytokine-induced activation and chemotaxis.
AB  - Human peripheral blood granulocytes previously were found to contain opioid delta
      2-receptors mediating stimulation by opioid peptides of chemotaxis. Studies
      presented in this work indicate that granulocytes also contain opiate alkaloid
      selective, opioid peptide-insensitive receptors mediating inhibition by morphine
      and other opiates of cytokine-induced activation and chemotaxis. Binding studies
      with [3H]morphine and [3H]diprenorphine ([3H]DPN) indicated the presence of
      receptor sites, at considerable density with affinities and selectivity for
      opiates comparable with those of the mu 3-receptor of human peripheral blood
      monocytes (macrophages). The influence of the guanosine 5'-triphosphate (GTP)
      analogue GppNHp on binding indicated that the granulocyte receptor was linked to
      a G protein. Morphine but not opioid peptides interfered with activation and/or
      chemotaxis of the granulocytes induced by TNF-alpha, IL-1 alpha, IL-8, and FMLP
      (chemotactic peptide). These effects of morphine were blocked by the antagonist
      naloxone. Levorphanol inhibited TNF-alpha-induced activation, and also
      potentiated the inhibition by morphine. Furthermore, in binding assays,
      levorphanol enhanced the affinity of the receptor for morphine. Dextrorphan had
      no effect on activation or chemotaxis, and it also had no effect on binding,
      indicative of stereoselectivity for the effect of levorphanol. It is concluded
      that human granulocytes contain opiate alkaloid-selective mu 3-receptors that
      mediate inhibitory effects of morphine on cellular activation by cytokines.

PMID- 7822802
TI  - Inhibition of mature IL-1 beta production in murine macrophages and a murine
      model of inflammation by WIN 67694, an inhibitor of IL-1 beta converting enzyme.
AB  - The proinflammatory cytokine IL-1 beta is synthesized by activated monocytes and
      macrophages as a 31-kDa, biologically inactive precursor that is proteolytically
      processed to the biologically active 17-kDa mature molecule by the IL-1 beta
      converting enzyme (ICE). WIN 67694, Z-Val-Ala-Asp-CH2O(CO)[2,6-(CI2)]Ph, is a
      potent, selective inhibitor of human ICE. In activated murine peritoneal
      macrophages, WIN 67694 inhibited the release of mature IL-1 beta with an IC50 of
      1.8 microM without any effect on the release of IL-1 alpha, IL-6, or TNF-alpha.
      The effect was specific to mature IL-1 beta release; the ICE inhibitor did not
      effect IL-1 beta RNA levels or precursor protein synthesis. In vivo, WIN 67694
      was also able to inhibit selectively the release of IL-1 beta in a dose-dependent
      manner in a subcutaneous tissue chamber implant model of inflammation. IL-1 beta
      levels in tissue chamber fluid were inhibited 35 and 55% at 10 and 100 mg/kg,
      respectively. IL-1 alpha, IL-6, and TNF-alpha levels were not affected. The
      ability to selectively inhibit mature IL-1 beta release in vivo with ICE
      inhibitors will allow for detailed studies of the role of IL-1 beta and ICE in
      inflammatory diseases.

PMID- 7822803
TI  - IL-1 is a potent inducer of eosinophil accumulation in rat skin. Inhibition of
      response by a platelet-activating factor antagonist and an anti-human IL-8
      antibody.
AB  - The aim of the present study was to investigate directly and characterize the
      ability of IL-1 beta in inducing eosinophil accumulation in vivo. For this
      purpose, we studied the recruitment of 111In-labeled eosinophils in rat skin in
      response to intradermally injected rat rIL-1 beta. Rat rIL-1 induced a dose
      dependent accumulation of 111In-labeled eosinophils, with the maximal response
      being detected at 5 x 10(-13) mol/site. This response was slow in onset,
      progressively increasing over the 4-h period investigated. Rat rIL-1 also induced
      a small level of edema, as measured by the local accumulation of i.v. 125I
      labeled albumin, which developed with a time course similar to that of 111In
      labeled eosinophil accumulation. Co-administration of the cytokine with the IL-1R
      antagonist, IL-1ra, or actinomycin D, significantly inhibited the 111In-labeled
      eosinophil accumulation, and reduced the edema formation, induced by rat rIL-1.
      In addition, the 111In-labeled eosinophil accumulation was significantly
      suppressed in animals treated with the PAF antagonist UK-74,505 or an anti-human
      IL-8 mAb DM/C7. These observations demonstrate for the first time that IL-1 beta
      is a potent inducer of eosinophil accumulation in vivo. Moreover, the results
      reveal that this activity of IL-1 beta is receptor mediated and dependent on the
      induction of proteins that may be involved in the local generation of secondary
      inflammatory mediators including PAF and an IL-8-like molecule. These findings
      are consistent with the view that endogenously generated IL-1 may play an
      important role in the recruitment of eosinophils at sites of allergic
      inflammation.

PMID- 7822804
TI  - IFN-gamma and lipopolysaccharide induce DNA binding of transcription factor PU.1
      in murine tissue macrophages.
AB  - The transcription factor PU.1, the Spi-1 oncogene product, is found principally
      in B cells and macrophages. PU.1 binds to a purine-rich sequence of DNA with a
      core consensus sequence of 5'-GAGGAA-3'. By using an electrophoretic mobility
      shift assay, we have been able to identify PU.1 in nuclear extracts of murine
      tissue macrophages. When macrophages are stimulated with IFN-gamma, an increase
      in PU.1 binding is observed. This increase is gradual, peaking at 6 to 9 h and
      decaying to basal levels 24 h after stimulation. The increase in PU.1 binding is
      unaffected by inhibiting protein synthesis, but is attenuated by either an
      inhibitor of the NA+/H+ antiporter or elevations in cAMP. In addition, we have
      found that low doses (1 ng/ml) of bacterial LPS induce PU.1 binding.

PMID- 7822805
TI  - Dexamethasone or cyclosporin A suppress mast cell-leukocyte cytokine cascades.
      Multiple mechanisms of inhibition of IgE- and mast cell-dependent cutaneous
      inflammation in the mouse.
AB  - In allergic diseases, exposure of sensitized subjects to allergen induces the
      activation of tissue mast cells that results in an immediate-type
      hypersensitivity response and, in some individuals, a a late phase response. We
      previously have reported that the neutrophil infiltration associated with IgE
      dependent cutaneous inflammation in mice is mast cell-dependent and that TNF
      alpha contributes significantly to this response. We report here that either
      dexamethasone or cyclosporin A can inhibit mouse mast cell TNF-alpha production
      in vitro, and that these agents also can significantly suppress the tissue
      swelling and leukocyte infiltration associated with two forms of TNF-alpha
      associated inflammation in vivo: the entirely IgE- and mast cell-dependent
      inflammation at sites of passive cutaneous anaphylaxis reactions and the entirely
      TNF-alpha-dependent inflammation that is elicited by the direct intradermal
      injection of recombinant mouse TNF-alpha. Taken together, our in vitro and in
      vivo findings in mice indicate that dexamethasone or cyclosporin A can have at
      least three actions that interfere with the pathogenesis of IgE, mast cell, and
      cytokine-dependent inflammatory reactions:suppression of the IgE-dependent
      increase in TNF-alpha mRNA by mast cells, inhibition of the IgE-dependent
      production of TNF-alpha protein by mast cells, and diminution of the
      responsiveness of target cells to TNF-alpha. Our findings in mice raise the
      possibility that similar actions of these agents in humans may account for some
      of the clinical efficacy of corticosteroids and cyclosporin A in allergic
      diseases.

PMID- 7822806
TI  - Inhibition of lipopolysaccharide-induced IL-1 beta transcription by cyclic
      adenosine monophosphate in human astrocytic cells.
AB  - The response to LPS includes synthesis by monocytes of the inflammatory mediator
      IL-1 beta. Although the intracellular signaling pathways activated by LPS that
      lead to IL-1 beta production have been studied extensively in monocytes, these
      pathways have not been investigated in astrocytes, an important source of IL-1
      beta in the central nervous system. cAMP has been implicated in LPS signaling as
      a positive regulator of IL-1 beta mRNA accumulation in monocytes. In this study,
      we demonstrate that in human astrocytes (both fetal and the astrocytoma cell
      line, U-373 MG), agents that elevate intracellular cAMP decrease LPS-induced IL-1
      beta mRNA accumulation. Elevated intracellular cAMP does not affect IL-1 beta
      mRNA stability, but inhibits LPS-induced transcription initiation of IL-1 beta in
      U-373 MG cells. Elevated intracellular cAMP may be a negative feedback regulatory
      mechanism to inhibit IL-1 beta production employed by astrocytes that (unlike
      monocytic cells) lack a glycosyl-phosphatidylinositol (GPI)-anchored form of the
      LPS receptor, CD14. Whether cAMP inhibits an LPS-inducible signaling pathway or
      negatively affects cAMP-dependent transcription factors remains to be determined.

PMID- 7822807
TI  - CDR3-independent gamma delta V delta 1+ T cell expansion in the peripheral blood
      of HIV-infected persons.
AB  - A majority of circulating gamma delta T cells in humans express the V delta 2
      variable segment associated with the V gamma 9 segment. A minor subset uses the V
      delta 1 gene mainly paired with a V gamma-chain from group I. Although little is
      known about the function and the Ags recognized by V delta 1 T cells, their
      expansion has been described in several diseases. Significant alterations of
      gamma delta subset distribution have been observed in PBMC from HIV-infected
      persons. In addition to their significant increase, gamma delta T cells showed an
      alteration in their subset representation because most of them expressed the V
      delta 1 receptor and, concomitantly, the V delta 2+ subset was under-represented.
      To gain insight into the mechanisms involved in this selective expansion, we
      characterized the V delta 1-J delta 1 junctional diversity in PBMC from healthy
      donors and HIV-infected individuals at different stages of the disease. We
      confirmed that the V delta 1 repertoire is restricted in most of the healthy
      donors. In HIV-infected subjects, we found that the increase of V delta 1 T cells
      is independent to a particular V gamma-chain expression, and the characterization
      of the TCR-delta diversity demonstrated a similar restricted V delta 1-J delta 1
      rearrangement pattern, not significantly different from the pattern of healthy
      donors. Moreover, no amino acid junctional motif could be identified either in
      control or in HIV-infected donors. This report demonstrates that the V delta 1
      selective expansion in the course of HIV infection is not the consequence of the
      emergence of some specifically CDR3-dependent expanded V delta 1 T cell clones.
      Interestingly, this subset showed an increased ability to be expanded in vitro in
      the presence of IL-2 alone and, although they did not harbor ex-vivo the
      phenotype of fully activated cells, they did express the activation marker CD38,
      a marker for disease progression. Altogether this report indicates that, although
      the patients' V delta 1 T cells seem to be in a pre-activated state, their
      selective expansion in the course of HIV infection is not the consequence of a
      peripheral CDR3-dependent antigenic selection.

PMID- 7822808
TI  - Balance of IL-1 receptor antagonist/IL-1 beta in rheumatoid synovium and its
      regulation by IL-4 and IL-10.
AB  - The spontaneous production of IL-1 beta (IL-1 beta) and IL-1 receptor antagonist
      (IL-1Ra) by rheumatoid arthritis (RA) synovium, and the regulation of their
      production by IL-4 and IL-10, were studied. Supernatants from cultured synovium
      pieces from 19 RA patients were assayed for IL-1 beta and IL-1Ra production using
      ELISA and RIA, respectively. After 10 days of culture, spontaneous production of
      IL-1Ra was 1.42 +/- 0.43 ng/ml/100 mg of synovium whereas spontaneous production
      of IL-1 beta was 4.03 +/- 0.90 ng/ml/100 mg of synovium (n = 19). The addition of
      IL-4 reduced IL-1 beta production by 2.3-fold (p = 0.001) and increased that of
      IL-1Ra by 2.8-fold (p = 0.003). IL-10 had no significant effect on IL-1Ra
      production and suppressed IL-1 beta production (primarily in samples producing
      high levels of IL-1 beta). However, IL-10 was less potent than IL-4 in
      suppressing IL-1 beta production. IL-1Ra was mainly produced by rheumatoid
      synovial monocytes/macrophages. IL-4 was more potent than IL-10 in inducing IL
      1Ra production by monocytes/macrophages purified from RA synovium, as well as
      from RA blood. Thus, RA synovium is characterized by an imbalance between IL-1Ra
      and IL-1 beta production, in favor of the latter. IL-4, and to a lesser extent IL
      10, shift this balance in favor of an anti-inflammatory situation.

PMID- 7822809
TI  - Activation of human thymocytes after infection by EBV.
AB  - The discovery of EBV in certain T cell malignancies and the expression of the EBV
      receptor, CR2/CD21, on a population of immature thymocytes, T lymphoblastoid cell
      lines, and childhood acute T lymphoblastic leukemia cells suggested that EBV
      receptor interactions on T cells may be of importance. We have shown that, within
      the thymus, a population of large, immature cells expresses CD21. EBV altered the
      activation responses of immature thymocytes in vitro. Triggering through CD2 is
      mitogenic for mature, but not immature, T cells. However, during infection by
      EBV, ligation of CD2 caused thymocytes to proliferate in the absence of exogenous
      cytokines. This function was a result of the interaction of EBV with its
      receptor, CD21, but was caused by infection rather than surface signaling,
      because neither specific mAb nor the P3HR-1 strain of virus mimicked the effect
      of B95-8. Immature thymocytes were infected by EBV, as determined by the
      internalization of the viral genome and its transcriptional activity. Consistent
      with the activity of B95-8, EBNA-2 transcripts were identified within infected
      thymocyte populations. In addition, components of the viral replicative pathway
      were expressed during infection of thymocytes. These components included
      transcription of BZLF-1, an early gene that characterizes EBV-infected B cells
      after disruption of latency. A second transcript was identified as encoding the
      recently characterized RAZ, which also is associated with replicative infection.
      The consequences of EBV infection of T cells at an early stage of differentiation
      may lead to failure of normal T cell repertoire development, autoimmunity, or
      malignancy.

PMID- 7822810
TI  - Selection of oligoclonal V beta-specific T cells in the intradermal response to
      Kveim-Siltzbach reagent in individuals with sarcoidosis.
AB  - Sarcoidosis is a multiorgan granulomatous disorder of unknown etiology
      characterized by noncaseating granulomas in involved tissues. A positive Kveim
      Siltzbach reaction is a granulomatous response to an intradermal injection of a
      suspension of sarcoid tissue extract in individuals with sarcoidosis. The
      protracted time course and granulomatous features of this reaction have a
      striking resemblance to the Mitsuda reaction in tuberculous leprosy, which
      suggests that the Kveim-Siltzbach reaction is a response to an unknown Ag(s). To
      evaluate whether this reaction is Ag-driven, an analysis of the TCR V beta
      repertoire in 15 Kveim-Siltzbach reaction sites was performed using a PCR
      technique and primers specific for 20 V beta gene families. Results of this
      analysis demonstrated a pattern of V beta expression dominated by expression of V
      beta 2, V beta 3, V beta 6, or V beta 8 to levels > 20% of total V beta gene
      expression in nine of 15 individuals. Analysis of paired biopsy and blood
      specimens revealed a preferential expression of specific V beta genes, such as V
      beta 3, V beta 5, and V beta 8, at sites of Kveim-Siltzbach reactions to levels
      four to seven times that of the corresponding peripheral blood. Sequence analysis
      demonstrated that preferential expression of specific V beta genes at Kveim
      Siltzbach reaction sites is oligoclonal. Furthermore, the dominant V beta 8
      sequence present at one of the reaction sites contained a sequence motif in the
      variable-diversity-joining junctional region previously identified in sarcoid
      lung and blood T cell populations. These results suggest that the Kveim-Siltzbach
      reaction is characterized by a limited TCR beta-chain repertoire consistent with
      an Ag-driven T cell immune response.

PMID- 7822811
TI  - T cell activation and anergy to islet cell antigen in type I diabetes.
AB  - Early exposure to cow milk proteins was linked to the development of type I
      diabetes by consistent epidemiology, and by feeding and tolerization studies in
      diabetes-prone rodents. Dietary BSA was suggested as the culprit because patients
      and relevant rodents have elevated anti-BSA Abs that precipitate the recently
      cloned protein, p69, from beta cell lysates. A total of 68 of 78 children with
      recent onset diabetes had BSA-reactive T cells at the time of diagnosis. Here we
      1) map the fine specificity of these T cells, 2) delineate a homologous peptide
      sequence near the N-terminus of p69, and 3) demonstrate T cell recognition of
      this p69 sequence (T cell epitope p69, Tep69) by patient T cells. The Tep69
      sequence is conserved in p69 of patients and diabetes-prone rodents. Whereas BSA
      triggers T cell proliferation, recombinant p69 and a synthetic Tep69 peptide
      induce early stages of T cell activation (IL-2R transcription) but insufficient
      IL-2 production and thus anergy. Exogenous IL-2 overrides anergy and allows
      proliferative expansion of p69-responsive T cells. In mixing experiments, p69 and
      Tep69 peptide prevented proliferative responses to BSA even at 100-fold smaller
      concentrations. These findings imply that high-affinity self-peptide triggers
      anergy, whereas low-affinity mimicry Ag triggers proliferative expansion of these
      T cells. This implies a disease model in which mimicry Ag would rescue
      autoreactive cells from ablation by self-Ag.

PMID- 7822812
TI  - IL-12 reverses cytokine and immune abnormalities in Sezary syndrome.
AB  - Cutaneous T cell lymphoma is a lymphoproliferative disorder typically
      characterized by skin invasion of clonally derived malignant CD4+ lymphocytes
      that phenotypically resemble mature Th cells. Sezary syndrome (SzS) represents an
      advanced form of cutaneous T cell lymphoma associated with generalized
      erythroderma and involvement of the peripheral blood by the malignant cell
      population. We have previously demonstrated aberrant cytokine production by PBMC
      in SzS characterized by increased IL-4 and deficient IL-2 and IFN-gamma
      production, as well as increased expression of mRNA for IL-4 and IL-5 within
      active skin lesions, suggesting that the clonal T cell population is derived from
      the Th 2 subset of helper T lymphocytes. These findings have been associated with
      a constellation of immune abnormalities that have been attributed to the cytokine
      abnormalities. Because IL-12 is a potent inducer of IFN-gamma production, and
      causes the activation of cytotoxic lymphocytes, we examined the production of IL
      12 by PBMC from SzS patients and whether IL-12 could alter the unfavorable
      cytokine balance typical of SzS and thus lead to correction of immune defects.
      Despite normal numbers of peripheral blood monocytes and normal TNF-alpha
      production, mean Staphyloccus aureus and LPS-induced IL-12 p40 and p70 production
      by SzS PBMC was significantly decreased compared with PBMC from normal controls.
      Mean IFN-gamma production by patient PBMC in response to PHA alone was depressed,
      but increased to levels comparable with normal after addition of 1 ng/ml IL-12.
      Pretreatment of PBMC for 24 h with IL-12, IFN-alpha, or both together resulted in
      a decrease in PHA-stimulated IL-4 production from a base line of 1818 pg/ml to
      1520, 1350, and 1058 pg/ml, respectively. Lastly, culture of patient PBMC with IL
      12 for 24 h also resulted in significant increases in NK activity against K562
      cells. These results indicate that PBMC from patients with SzS manifest a defect
      in IL-12 production and that the cytokine abnormalities associated with SzS can
      be favorably altered by IL-12.

PMID- 7822813
TI  - Influence of IL-1 receptor blockade on the human response to endotoxemia.
AB  - Although the experimental administration of IL-1 induces several aspects of the
      inflammatory response, such as fever, tachycardia, and acute phase proteinemia,
      the contribution of IL-1 to the human responses to injury or infection remains
      unclear. A specific IL-1R antagonist (IL-1ra), which effectively blocks the
      actions of IL-1, was utilized to evaluate the influence of endogenous IL-1 during
      experimental human endotoxemia. Eighteen healthy volunteers each underwent one
      control study day, followed 3 days later by one of three randomly chosen
      treatments: a 6-h infusion of IL-1ra alone (133 mg/h), 20 U/kg national reference
      endotoxin alone, or both endotoxin and IL-1ra infusion. IL-1ra administration
      alone was not associated with any observable response. Despite achieving high
      circulating levels of IL-1ra (34 +/- 3 micrograms/ml), there were no significant
      differences in hemodynamic parameters, core temperature, or resting energy
      expenditure in those endotoxemic volunteers receiving IL-1ra when compared with
      those who did not. Furthermore, leukocyte kinetic and circulating cytokine, acute
      phase protein, and endocrine responses were similar in both endotoxemic groups.
      However, IL-1 blockade did significantly reduce the subjective severity of
      symptoms experienced by the endotoxemic volunteers (p < 0.05). This study
      demonstrates that an endogenous IL-1 response does not play a significant role in
      the hemodynamic, immunologic, and metabolic responses to mild endotoxemia in
      humans.

PMID- 7822814
TI  - Distinct signal transduction in mouse CD4+ and CD8+ splenic T cells after CD28
      receptor ligation.
AB  - Current evidence suggests that recognition of Ag/MHC by the TCR alone is
      insufficient to lead to T cell proliferation or effector function. For a Th cell
      to produce sufficient IL-2 to allow autocrine-driven clonal expansion, there is a
      requirement for so-called "costimulatory" or "accessory" signals in addition to
      TCR ligation by Ag/MHC. Although the first signal delivered by TCR ligation has
      been well characterized, information regarding the biochemical nature of second
      signals is limited. In the present report, using a newly generated mAb specific
      for CD28, signal transduction by the CD28 receptor has been studied in mouse
      splenic T cells. When freshly isolated splenic T cells were assessed, cross
      linking of CD28 by mAb did not induce increases in intracellular calcium
      concentration were assessed, cross-linking of CD28 by mAb did not induce
      increases in intracellular calcium concentration whereas TCR cross-linking was
      able to induce calcium mobilization. In contrast, when T cells were activated by
      phorbol ester treatment or by in vitro culture, CD28 ligation was able to induce
      calcium mobilization in 60 to 70% of splenic T cells. Unexpectedly, the CD28
      induced calcium response was mainly limited to T cells of the CD4+ subset,
      whereas both CD4+ and CD8+ T cell subsets showed increases in [Ca2+]i of similar
      magnitude after CD3 epsilon ligation. The temporal nature of the CD28-induced
      signal was also different from TCR-induced calcium mobilization. CD28-induced
      signals were delayed in onset and sustained in duration in contrast to TCR
      signals that had short latency and brief duration. Differential expression of
      CD28 on the surface of activated CD4+ or CD8+ T cells did not appear to account
      for the differences in signal transduction between the two T cell subsets. The
      preferential responsiveness of the CD4+ T cell population to CD28-induced
      signaling was also observed in downstream events such as the induction of IL-2R,
      CD69 expression, and in cellular proliferation. These results indicate that the
      costimulatory signal delivered by CD28 may have fundamentally different
      biochemical properties in CD4 and CD8 T cell subsets, and therefore the
      functional role of CD28 may differ in these T cell subsets.

PMID- 7822815
TI  - Extension of the four-parameter logistic model for ELISA to multianalyte
      analysis.
AB  - The standard implementation of enzyme-linked immunosorbent assay (ELISA) for
      single analytes can lead to false conclusions if cross reacting compounds are
      present in the sample. This paper discusses the extension of the usual four
      parameter logistic model for ELISA to the case of multiple cross-reacting
      analytes. The use of the extended model in multianalyte analysis (MELISA) is
      illustrated and compared with a more simplistic approach. Data on the analysis of
      a binary mixture of s-triazines suggests the superiority of the proposed model.
      This model is also suitable for other forms of immunoassay that use the four
      parameter logistic curve.

PMID- 7822816
TI  - An improved fluorescence assay for the determination of lymphocyte-mediated
      cytotoxicity using flow cytometry.
AB  - The use of the chromium-release assay to determine cytotoxicity of effector
      against target cells has various limitations mostly due to the inherent
      properties of the radioactive substance. We have developed an improved flow
      cytometric method that is able to measure cytotoxicity, based on two fluorescent
      dyes. Calcein-AM, a non-fluorescent substance which is intracellularly converted
      to the green fluorescent calcein by esterase activity in viable cells, is
      initially used to stain target cells. After incubating targets with effectors for
      2 h, ethidium homodimer-1, a red DNA stain non-permeable to viable cells, is
      added. Dead target cells are distinguished by their double (green-red) staining.
      Data analysis is performed by gating the regions of living target, dead target
      and living effector cells, based on appropriate controls. Non-specific events are
      subtracted from the dead target region and the ratio of specific dead target
      events to total target events is expressed as percent cytotoxicity. The method is
      used to quantify natural killer (NK) and lymphokine-activated killer (LAK)
      activities against the human K562 and Daudi cell lines and the murine YAC-1 and
      L1210 cell lines respectively, as well as cell-mediated lympholysis (CML) exerted
      by tumor-infiltrating lymphocytes (TIL) against autologous and allogeneic human
      breast cancer tumor cells. The method is fast, reliable and correlates well with
      the standard 51Cr-release assay.

PMID- 7822817
TI  - Assessment of cell proliferation by means of an enzyme-linked immunosorbent assay
      based on the detection of the Ki-67 protein.
AB  - A new ELISA system for the estimation of cell proliferation based on the
      detection of the Ki-67 protein is described. This protein has turned out to be
      strictly correlated to all active parts of the cell cycle, i.e., G1, S, G2, and
      mitosis, but is absent in G0. In addition, it is not detectable during DNA
      repair. In cultures of cell line cells as well as stimulated peripheral blood
      cells the values obtained with this ELISA system paralleled the [3H]thymidine
      uptake in different cell cultures. Thus, this assay provides a simple, non
      radioactive assessment of proliferation of cultured cells.

PMID- 7822818
TI  - A flow cytometric long-term cytotoxicity assay.
AB  - A method to evaluate cytotoxic effects applicable over a wide range of incubation
      times has been developed. It is based on quantification by flow cytometry of dead
      and viable target cells stained by covalently binding the fluorescent dye
      fluorescein isothiocyanate (FITC). The staining with FITC did not affect cell
      viability and growth parameters and was stable enough to identify target cells
      for at least 2 days. The flow cytometric analysis of the cell mixture was
      performed in a test system with activated CD8+ lymphocytes as effector cells and
      melanoma M21 cells as targets in the presence of appropriate bispecific
      antibodies and revealed a rather complex pattern composed of several distinct
      cell subsets which were identified by use of antibodies to lymphocyte antigens.
      The assay compared favourably with results from a conventional 51Cr release assay
      obtained after 4 h and 8 h of incubation and from a target cell adherence assay
      obtained after 24 h of incubation. The application of the method described herein
      is especially advantageous for the evaluation of long-term cytotoxic effects.
      Furthermore, it provides valuable multi-parameter information which is useful for
      elucidating mechanisms of cytotoxicity.

PMID- 7822820
TI  - Cytofluorometric quantification of IgE and IgE receptors on individual mast
      cells.
AB  - Information about the IgE receptor and IgE content of mast cells under different
      conditions in vivo is essential for further understanding the functions of the
      mast cell-IgE system. A cytofluorometric method for measuring cell-bound IgE on
      individual mast cells was therefore explored using peritoneal mast cells of
      Sprague-Dawley rats infected with the nematode N. brasiliensis and rat basophilic
      leukaemia cells (RBL-1) as experimental models. We systematically studied the
      effects of variables such as fixation, incubation time, temperature and
      concentrations of antibody on the fluorescence emission of the mast cells.
      Optimum conditions were selected for the quantitative measurement of IgE at the
      single-cell level using direct labelling with FITC-conjugated goat anti-rat
      IgE(Fc). Polystyrene beads with a defined fluorophor content and a fluorescent
      uranyl glass were used to standardise the measurement procedure. A linear
      relationship between fluorescence intensity and IgE concentration was obtained by
      fluorescence measurements on RBL-1 cells incubated in rat IgE. In the case of rat
      peritoneal mast cells it was possible to saturate the IgE receptors by incubating
      the mast cells in rat IgE. By measuring the mast cells before and after IgE
      incubation, the relative content of IgE, the relative number of IgE receptors and
      the degree of receptor saturation could be estimated. In this way we measured the
      IgE content of peritoneal mast cells of Sprague-Dawley rats maintained under
      pathogen-free conditions. The distribution of IgE content in the mast-cell
      populations was extremely variable. Up to 30% of the mast cells in individual
      populations contained little or no IgE, but very few if any of the cells lacked
      IgE receptors. On average, 60-70% of the receptors available for binding were
      occupied by IgE in these normal rats.

PMID- 7822819
TI  - Theoretical and experimental epitope mapping of thymosin beta 4.
AB  - Two rabbit polyclonal antisera, one directed against thymosin beta 4 and the
      other one against the peptide fragment thymosin beta 4 (1-14) were characterised
      by epitope mapping. Hexapeptides representing the whole sequence of the native
      peptide and overlapping by one amino acid were synthesised on polystyrene pins.
      The antigenic determinants were identified in microtitre plates with an ELISA
      procedure. The polyclonal serum against thymosin beta 4 detected three epitopes
      (N-terminal, mid-region and C-terminal) whereas the polyclonal serum against the
      fragment contained only antibodies specific for the N-terminal epitope. These
      experimental results are consistent with theoretical predictions.

PMID- 7822821
TI  - On the interaction between single chain Fv antibodies and bacterial
      immunoglobulin-binding proteins.
AB  - Using four bacterial immunoglobulin-binding proteins, we have analyzed the
      binding characteristics of a panel of 34 human single chain Fv antibodies,
      expressed in E. coli and with known specificity and sequence. Several of the
      single chain Fv antibodies showed affinity for staphylococcal protein A and
      peptostreptococcal protein L, but not for the streptococcal proteins G or H. The
      affinity of the binding was higher for protein L (4.5 and 1.4 x 10(9) M-1) than
      for protein A (7.7 and 6.7 x 10(8) M-1), using the two single chain Fv antibodies
      displaying the strongest binding activity to these ligands. The binding was shown
      to be specific by Western blotting, and the single chain Fv antibodies could be
      purified from crude bacterial culture media by affinity chromatography on protein
      L- or A-Sepharose. Protein A, which has affinity for the VH domain of the scFv
      antibodies, was tested against scFv antibodies containing VH1, VH3, VH4 and VH5
      domains, and its binding was restricted to approximately half of the scFv
      antibodies with a VH3 domain. Protein L, which has affinity for the VL domain,
      was tested against kappa 1, kappa 4, lambda 1, lambda 2 and lambda 3 domains, and
      it bound all kappa 1 domains, one lambda 2 and one lambda 3 domain. Comparison of
      the amino acid sequences of binding and non-binding VL domains demonstrated that
      amino acid residues crucial to the binding of protein L were distributed over a
      large area outside the hypervariable antigen-binding regions.

PMID- 7822822
TI  - Reduction of escapee formation in flow cytometric analysis of lymphocyte subsets.
AB  - Most experienced flow cytometrists performing immunophenotyping of lymphocyte
      subsets are aware of the escape phenomenon, in which some positive cells are
      found outside a lymphocyte gate based on forward and right angle scatter.
      However, little information is available on the levels of escapees formed with
      different antibodies, the roles of fluorochromes and lysing agents, the mechanism
      explaining the phenomenon, or methods to reduce it. We thus performed a
      systematic analysis of the escapee phenomenon to clarify these issues. A panel of
      monoclonal antibodies, including a phycoerythrin (PE) conjugate and a fluorescein
      isothiocyanate (FITC) conjugate of the same antibody from one manufacturer, was
      used to treat whole blood specimens, after which red cells were lysed using 0.15
      M ammonium chloride (AmChl). The percentages of gated lymphocytes expressing CD3,
      CD8, CD19, and HLA-DR, but not CD2, CD4, CD16, and CD25, were significantly lower
      in FITC-stained versus PE-stained preparations. Correlated analysis of green
      fluorescence and forward scatter showed that, on average, 18% of CD3+ events, 24%
      of CD8+ events, and 25% of CD19+ events were escapees when using the FITC
      conjugate. In dual color analysis, CD3+ escapees were positive for CD62-P, CD13,
      and CD14, indicating that the escapee events consisted of FITC-anti-CD3-coated
      lymphocytes complexed with platelet-coated myeloid cells. In studies of the role
      of lysing agent, essentially no escapees were found in specimens treated with
      FACS lysing solution, which contains formaldehyde. We therefore included a
      similar denaturing agent, paraformaldehyde (0.1%), in the AmChl lysing agent, and
      found that the occurrence of escapees was markedly reduced. These findings show
      that the escapee phenomenon occurs when using some FITC-conjugated monoclonal
      antibodies in conjunction with AmChl lysing agent, and can be reduced by
      inclusion of paraformaldehyde in the lysing agent.

PMID- 7822823
TI  - Construction of a human B cell line, TKHMY, suitable for production of stable
      human hybridomas.
AB  - In order to produce stable hybridomas for generation of human monoclonal
      antibodies (HMAbs), an attempt was made to construct a suitable human parental B
      cell line with double selection markers, the strategy being to produce HMAbs by
      fusing a parental B cell line with EBV-transformed B cells producing specific
      antibodies. The resultant TKHMY cell line, constructed by transfecting the
      Blasticidin S resistant (bsr) gene into the HAT sensitive human B cell line LTR
      228 could be used as a fusion partner for very efficient production of human
      hybridomas. Secretion of IgG monoclonal antibodies to antigens on lung cancer
      cells by one such hybridoma was very stable, indicating that this TKHMY cell line
      has practical advantage in the area of antibody production.

PMID- 7822824
TI  - The use of caprylic acid for the extraction of the immunoglobulin fraction from
      egg yolk of chickens immunised with ovine alpha-lactalbumin.
AB  - The extraction and purification of serum-derived immunoglobulin fraction in the
      egg yolk of hens by the combined treatment of the raw egg yolk with caprylic
      (octanoic) acid and ammonium sulphate is described. This simple two-step method
      proved to be both rapid, reproducible and suitable for batch processing of pooled
      egg yolk. The method recovered in excess of 130 mg of immunoglobulin per egg
      yolk. Two chickens were inoculated at two weekly intervals with 100 micrograms
      each of ovine alpha-lactalbumin over a ten week period. The alpha-lactalbumin
      antigen was purified by a hydrophobic-interaction chromatographic procedure and
      further purified by a gel excision-elution process. No precipitating antibodies
      could be demonstrated in gel diffusion techniques with this antibody. The
      specificity and specific activity of the antibody were monitored by western
      blotting and demonstrated the presence of highly specific antibodies to ovine
      alpha-lactalbumin in the treated egg yolk. The extraction procedure had no
      adverse effects on antibody titre. We concluded, and confirmed previous reports,
      that the use of chickens for the production of highly specific antibodies to
      mammalian proteins with particular reference to milk proteins presented numerous
      advantages over conventional procedures.

PMID- 7822825
TI  - Application of the gel shift assay to study the affinity and specificity of anti
      DNA autoantibodies.
AB  - We have demonstrated that the gel shift assay, a powerful method to study
      protein.DNA interactions under equilibrium conditions, is both an accurate and
      precise method to measure the affinity of anti-DNA.DNA immune complexes. One
      difficulty in performing gel shift assays is disruption of protein.DNA equilibria
      during the time needed for complexes to enter the gel matrix. However, we have
      found that highly cross-linked polyacrylamide gels which are known to form non
      restrictive matrices, do not perturb anti-DNA.DNA complexes. Using anti-ssDNA
      BV04-01 as a model antibody, we find good agreement between the dissociation
      constants (Kd) measured in the gel shift assay using a 5.4% polyacrylamide gel
      cross-linked with 0.6% (bis)acrylamide, and those obtained previously by
      fluorescence quenching. Because gel shift assays require only nanogram quantities
      of analyte and can be performed in several hours, it is well suited for a range
      of anti-DNA binding studies.

PMID- 7822826
TI  - Tumor necrosis factor (TNF) alpha quantification by ELISA and bioassay: effects
      of TNF alpha-soluble TNF receptor (p55) complex dissociation during assay
      incubations.
AB  - It has been previously reported that different quantitative results can be
      obtained when TNF alpha is measured in biological fluids by bioassay and
      immunoassay. This is thought to be related to the presence of antigenic forms of
      TNF alpha that cannot be detected by bioassay, such as complexes with soluble
      receptors (sTNF-R) or TNF alpha monomers. In this work we have observed
      discrepancies between antigenic and bioactive TNF alpha even when we used a
      sandwich-ELISA, unable to detect TNF alpha monomers, based on antibodies that
      bind epitopes overlapping with the soluble-receptor binding site of TNF alpha.
      Moreover, we found that antigenic TNF alpha levels in the presence of p55-sTNF-R
      (sTNF-R1) measured by different immunoassays were variable, depending on the
      immunoreagents and incubation time. To investigate whether TNF alpha-soluble
      receptor complex dissociation occurring during assay incubations contributes to
      the variability of results, we studied the kinetics of TNF alpha-soluble receptor
      interactions and examined the effect of complex dissociation using different
      analytical systems. TNF alpha association (k(on)) and dissociation (koff) rate
      constants with sTNF-R1, measured by real-time biospecific interaction analysis,
      were 5.01 x 10(5) s-1 M-1 and 2.8 x 10(-4) s-1, corresponding to an equilibrium
      constant (Kd) of 0.59 nM and to a half life for these complexes of 38 min.
      Complex dissociation and differential changes in the TNF alpha-sTNF-R1 bound:free
      ratio, in different analytical systems, markedly affects TNF alpha
      quantification.

PMID- 7822827
TI  - Efficient optimization of ELISAs.
AB  - In this paper, we describe a technique for using the statistical method of
      fractional factorial design in the optimization of an ELISA. Fractional factorial
      design dramatically reduces the total number of experiments required in the
      optimization. In addition, this technique enables us to determine the parameters
      that give the maximum sensitivity range with the most accuracy for the ELISA
      studied.

PMID- 7822828
TI  - A sensitive ELISA for measuring the adhesion of leukocytic cells to human
      endothelial cells.
AB  - A new, sensitive ELISA using monoclonal antibodies reactive with surface
      molecules specific for various leukocytes was devised to measure the attachment
      of these cells to cultured monolayers of human umbilical vein endothelial cells.
      Preparations of peripheral blood mononuclear cells, a human monocytic cell line
      (THP-1) and a human lymphoblastic T cell line (MOLT-4) were used to test the
      sensitivity of this method and compare it with the conventional 51Cr-radiolabeled
      cell assay. The extent of adhesion to endothelial cells was assayed by measuring
      the optical density produced by a complex of peroxidase-labeled streptavidin,
      biotin-conjugated F(ab')2 anti-mouse Ig and monoclonal antibody on fixed
      leukocytic cells that had adhered to endothelial cells. This method is fast and
      sensitive, eliminates the use of radioisotopes, and, because the detection uses a
      specific marker on the cell of interest, can be used in preparations of
      unseparated mixtures of cells. As this is a microassay, using relatively small
      number of cells and reagents, the methodology can be applied to screen a large
      number of therapeutic agents that may regulate adhesion. Using this method, the
      anti-inflammatory corticosteroid, dexamethasone, was found to inhibit the
      adhesion of THP-1 and MOLT-4 cells to cytokine-activated endothelial cells.

PMID- 7822829
TI  - Multicolor flow cytometric analysis of the CD45 antigen provides improved
      lymphoid cell discrimination in bone marrow and tissue biopsies.
AB  - Samples from bone marrow or non-hematopoietic tissue such as solid organ biopsies
      often contain an excess of non-leukocytes exhibiting lymphocyte-like light
      scatter characteristics, making it sometimes difficult to define satisfactory
      light scatter lymphocyte gates. To circumvent this, we describe here a
      multiparametric method of identifying lymphoid cells by expression of the CD45
      antigen, in conjunction with light scatter parameters. A 'third color'-conjugated
      anti-CD45 antibody was included with every FITC/PE double staining, thereby
      permitting live or list mode analysis gating on CD45 positive cells. The triple
      staining technique was applied to (a) human bone marrow, showing that special
      attention has to be given to the enumeration of B cells, and (b) to liver
      biopsies, where gating on CD45 fluorescence and orthogonal light scatter was
      shown to clearly resolve all lymphocyte subsets from debris. All cell types
      examined in tissue biopsies as well as T and NK cells in bone marrow were best
      distinguished by gating on bright CD45 expression in conjunction with low
      orthogonal light scatter, while accurate identification of marrow B cells relied
      upon including all levels of CD45 intensity. The multicolor gating procedure,
      aimed mainly at immune-monitoring of non-malignant tissues, is applicable to most
      kinds of single cell samples, and may prove to be an aid for lymphocyte gating in
      cases where leukocyte populations are not clearly resolved on a light scatter
      basis alone.

PMID- 7822830
TI  - Characterisation of monoclonal antibodies against human interleukin-10 and their
      use in an ELISA for the measurement of this cytokine.
AB  - Biological and biochemical characteristics of monoclonal antibodies (MABs) raised
      against human interleukin-10 (IL-10) are described as well as their use in the
      design of a specific ELISA for the measurement of the cytokine. 21 murine anti
      human interleukin-10 (IL-10) MABs were obtained by fusion of splenocytes from
      mice immunized against human recombinant IL-10 with SP2/0 myelomatous cells.
      These antibodies define three major antigenic areas on the IL-10 molecule, one of
      which comprises epitopes involved in receptor binding and induction of biological
      activity. They recognize recombinant human IL-10 with affinities ranging from 1.3
      x 10(-7) to 3 x 10(-11), as well as natural IL-10. Most of them also recognize
      viral IL-10 (vIL-10) encoded by the Epstein-Barr virus (EBV). A specific human-IL
      10 ELISA has been developed using two MABs (18 and 19) as capture antibody and
      one MAB (17) as detector. The sensitivity (3 pg/ml), precision (intra-assays <
      4%), reproducibility (interassay < 3%), and accuracy (recoveries, ranging between
      84 and 107%, in several fluids) of the assay, plus its excellent performance in
      dilution tests, and the lack of interference when in the presence of possible
      cross-reactive substances, permits accurate cytokine measurement in biological
      fluids such as serum, plasma, bronchoalveolar lavage, urine and culture
      supernatants. Using the assay, IL-10 was measurable in the plasma of patients
      with septic shock (range 11-2740 pg/ml) whereas IL-10 plasma levels were < 7.8
      pg/ml in healthy volunteers.

PMID- 7822831
TI  - A novel multispecific competitor fragment for quantitative PCR analysis of
      cytokine gene expression in rats.
AB  - Competitive polymerase chain reaction (PCR) is a sensitive method for
      quantification of cytokine mRNA expression. Co-amplification of an internal
      standard serves as control for comparing the efficiency of PCR in different
      samples. We have developed a novel control fragment for multiple analyses of rat
      cytokine gene expression containing primers for IL-1 beta, IL-2, IL-4, IL-5, IL
      6, IL-10, TNF-alpha, TGF-beta 1, IFN-gamma and MIP-2. Additional primers were
      incorporated to analyse the content of T cells (CD3), activated T cells (CD25)
      and housekeeping genes (beta-actin and HPRT). As an example we demonstrate
      analysis of IL-2 mRNA expression in small pieces of kidney tissue obtained from
      rats after kidney allotransplantation. The IL-2 expression decreased tenfold
      during treatment with an anti-rat CD4 monoclonal antibody as compared to
      untreated animals.

PMID- 7822832
TI  - Development of a radioimmunoassay method for ethynylestradiol in plasma using a
      monoclonal antibody.
AB  - An ethynylestradiol (EE2) radioimmunoassay method (RIA) using a monoclonal
      antibody (MAB) reagent is described. 76 plasma and 67 buffer blanks spiked with
      known concentrations of EE2 were used as positive samples. The steroid was
      extracted using dichloromethane method with an extraction efficiency of 78 +/-
      2.6%. The plasma extracts were not purified. Separation of the free from bound
      tritiated EE2 was by centrifugation with dextran-coated charcoal suspension in
      phosphate-gelatin buffer. Within 95% confidence limits, the sensitivity of the
      assay was 10 pg/ml in buffer samples, and 43 pg/ml in unpurified plasma samples.
      The accuracy and precision of the method were lower for the plasma samples than
      for the buffer solutions but within accepted limits (i.e., 80-120% for accuracy,
      and up to 20% for precision). The mean recovery accuracy (R) of the method for
      measuring 38 pg/ml EE2 in buffer was 101 +/- 0.9% (n = 67), while for 2.39 pg/ml
      to 18.0 pg/ml EE2 in plasma was 97 +/- 12% (n = 76). The buffer solutions and
      plasma samples containing 600 pg/ml EE2 had a mean R of 102% (n = 18) and 90% (n
      = 16), respectively. The average interassay variation (%CV) between buffer
      samples was 14 +/- 1.2%, and between plasma samples was 19 +/- 8%. Plasma samples
      with 18 pg/ml and 2.39 pg/ml EE2, together with the blank negative plasma samples
      showed high interassay variations (CV > 20%). Except for the above samples,
      however, the precision of the method in all sample groups was within accepted
      limits. The intra-assay variation of replicate assays of a single plasma sample
      containing 1.2 ng/ml EE2 and 4 ng/ml levonorgestrel was 13% (n = 7). In the
      presence of very high concentration of closely related levonorgestrel, the R of
      the method was 106%. The increase in average variability (%CV) between results
      for the plasma samples (CV 19 +/- 8%) over that of the spiked buffer solutions
      (CV 14 +/- 1.2%) suggest some possible interference by co-extracted materials
      from plasma, for example lipids, which interfered in the ligand-antibody
      reactions. Further investigation may prove that a pre-assay purification of the
      sample, e.g., HPLC, would eliminate this interference. Nevertheless, the
      immunoassay described above completely eliminates the problem of cross-reactivity
      caused by the natural estrogens in plasma with the conventional polyclonal
      antibodies. It possesses an acceptable intra- and interassay variation with very
      high specificity to EE2.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7822833
TI  - A lactate dehydrogenase (LDH)-based immunoassay for detection of cell surface
      antigens and its application to the study of MHC class I-binding peptides.
AB  - A lactate dehydrogenase (LDH)-based immunoassay, referred to as CPEIA (cell
      panning enzyme immunoassay), has been developed for the detection of cell-surface
      antigens. CPEIA is similar to a panning assay, in that it is based on the capture
      of cells bearing an antigen of interest by means of an antibody immobilized to a
      96-well microtiter plate. Attachment of the cells is then measured by addition of
      a substrate for the intracellular enzyme lactate dehydrogenase. The substrate
      solution also contains the nonionic detergent Triton X-100 to lyse the cells and
      release LDH, which converts the substrate p-iodonitrotetrazolium violet (INT)
      from yellow to red. The intensity of the color resulting from the LDH-catalyzed
      reaction is proportional to the number of cells bound to the plate. The procedure
      does not require fixation of the cells, centrifugation, and blocking steps,
      resulting in a more convenient assay. CPEIA has been used for the detection of
      MHC class I antigens and other molecules on the surfaces of mouse cell lines and
      concanavalin A (ConA)-stimulated T lymphocytes. In addition, the assay has been
      used to detect peptide binding to Db and Kb MHC class I molecules on the surface
      of the mutant cell line RMA-S. The half-maximal responses for peptide-MHC class I
      interactions at different peptide concentrations can be determined with the
      assay, allowing the apparent dissociation constants to be calculated.

PMID- 7822834
TI  - Radioresistance of interleukin-2 producing cryopreserved human peripheral blood
      mononuclear cells.

PMID- 7822835
TI  - Thiophilic adsorption: rapid purification of F(ab)2 and Fc fragments of IgG1
      antibodies from murine ascitic fluid.
AB  - A thiophilic adsorption method has been developed for rapid purification and
      separation of mouse F(ab)2 and Fc fragments obtained after proteolytic digestion
      of IgG1 monoclonal antibodies. Partially purified Mabs were digested with papain.
      Thiophilic chromatography was performed using stepwise elution with decreasing
      concentrations of ammonium sulphate. Most contaminating proteins did not react
      with the thiophilic adsorbent, and chromatography efficiently resolved the F(ab)2
      and Fc fragments, as judged by electrophoresis. Fractions containing the F(ab)2
      fragments retained about 90% of the total antibody activity loaded onto the
      column.

PMID- 7822836
TI  - Solution-phase binding of monoclonal antibodies to bee venom phospholipase A2.
AB  - The binding of monoclonal anti-bee venom phospholipase A2 antibodies to their
      antigen was monitored by size-exclusion high performance liquid chromatography.
      As judged by this panel of six antibodies, honeybee venom phospholipase A2
      contains five binding sites, three of which are completely independent epitopes.
      The study revealed that this PLA2 can accommodate three different antibodies
      simultaneously. The results demonstrate the utility of size-exclusion high
      performance liquid chromatography in epitope analyses, such as its ability to
      compare the relative expansiveness and conformational state of the epitopes and
      to enumerate the antibodies that the antigen can accommodate simultaneously. The
      data provide compelling evidence that one of the monoclonal antibodies, M5 (which
      activates the enzyme), recognizes a different conformation of phospholipase A2
      than do the other antibodies. The results also demonstrate that different pairs
      of monoclonal antibodies differ in their predilection to form high molecular
      weight complexes with the antigen.

PMID- 7822837
TI  - Evaluation of alternative CD4 technologies for the enumeration of CD4
      lymphocytes.
AB  - Enumeration of CD4+ T cells from persons infected with the human immunodeficiency
      virus (HIV) is important. Traditionally this measurement has been calculated by
      multiplying the percent of lymphocytes that are CD4+ T cells (from flow
      cytometry) and the number of lymphocytes per microliter of blood (from hematology
      measures). Recently, several manufacturers have developed new techniques for
      determining absolute numbers of CD4+ and CD8+ cells without the need for the flow
      cytometer and hematology analyzer. We evaluated these methods for accuracy
      (comparison with traditional methodology) and precision (variability of replicate
      determinations) as well as for use with specimens older than 1 day. Precision of
      the assays as determined by the coefficients of variation (CV) from replicates
      varied from about 3% to about 12%, depending on the assay and the HIV status of
      the patient. Correlation coefficients of test method results with the standard
      methodology (r) were all greater than 0.9, and in most cases slopes were close to
      1.0 for both CD4 and CD8. Though each methodology will meet different
      requirements in the laboratory, our results indicate that these assays are all
      acceptable for enumerating CD4 and CD8 cells in HIV+ as well as HIV- patients.

PMID- 7822838
TI  - Flow cytometric evaluation of LDL receptors using DiI-LDL uptake and its
      application to B and T lymphocytic cell lines.
AB  - Low density lipoprotein receptors (LDL-R) on Daudi Burkitt's lymphoma (BL) cells
      were assessed using fluorescent DiI (3,3'-dioctadecylindocarbocyanine iodide)-LDL
      and flow cytometric analyses. Receptor-specific binding of DiI-LDL is followed by
      internalization of the bound complex and lysosomal hydrolysis of the ligand.
      Increase in the fluorescence intensity per cell is hence used as a measure of DiI
      LDL uptake and, implicitly, as an indication of LDL-R presence. Our results show
      that uptake was observed in > 98% of the Daudi cells, and the level of uptake was
      significant and clearly distinguishable from autofluorescence, suggesting that:
      (a) this assay is comparable to the iodinated LDL uptake assay, although the ED50
      values for the ligands are different; (b) this assay is comparable to the flow
      cytometric detection of LDL-R using a commercial antibody directed against the
      receptor itself, and superior to a similar assay based on an antibody directed
      against membrane-bound LDL; (c) LDL uptake could be monitored along with
      transferrin uptake, suggesting that multiple endocytic receptor activities can be
      concurrently studied; (d) DiI-LDL uptake can be examined along with fluorescein
      conjugated anti-CD10, -CD19, and -CD71, with little cross-interference, offering
      the added advantage that endocytic uptake and phenotyping can be simultaneously
      monitored; (e) the expression of LDL-R is intrinsically elevated in diverse cell
      lines such as Daudi, Raji, Ramos, Jurkat, and WIL2-NS, but not in normal
      lymphocytes. Our results therefore indicate that flow cytometric analysis of DiI
      LDL uptake has potentially useful applications in the detection and study of
      endocytic receptor LDL-R in B and T lymphocytic cell lines.

PMID- 7822839
TI  - Development of an enzyme-linked immunosorbent assay (ELISA) combined with a
      streptavidin-biotin and enzyme amplification method to detect anti-2,3-di-o
      acyltrehalose (DAT) antibodies in patients with tuberculosis.
AB  - IgG antibodies against the 2,3-di-o-acyltrehalose glycolipid of Mycobacterium
      tuberculosis were determined in a set of 49 sera from patients with pulmonary
      tuberculosis and 65 negative control subjects. We compared a conventional ELISA
      method using a beta-galactosidase anti-human IgG conjugate developed with ONPG,
      with an amplification ELISA system constituted of an anti-human IgG biotinylated
      conjugate, a streptavidin-alkaline phosphatase complex, and NADP as a substrate.
      The resulting NAD was measured by using a redox enzymatic recycling system of
      alcohol dehydrogenase, diaphorase and iodonitrotetrazolium as chromogen. With
      specificity set at 92.31% in both methods, we obtained a sensitivity of 42.86% in
      the conventional method and a sensitivity of 61.22% in the amplified method. We
      conclude that by using a more sensitive method we can detect cases that otherwise
      could be identified as false negatives.

PMID- 7822840
TI  - Validation of a quantitative ELISA for comparison of monoclonal antibody
      affinities for isolates of bluetongue virus.
AB  - The ability of an ELISA-based system to reliably assess the relative affinities
      of separate monoclonal antibodies (MAbs) for heterologous isolates of bluetongue
      virus (BTV) was tested. The demonstration that a BTV serogroup-specific MAb
      (20E9B7G2) possessed equivalent binding properties with the majority of virus
      isolates tested, permitted a reliable estimation of the relative amount of
      individual test viruses present in the assay. Subsequent correction for the
      relative amounts of test viruses and homologous virus present, then allowed
      monoclonal antibody affinities for heterologous virus isolates to be
      quantitatively expressed as a function of their homologous binding level and
      enabled comparisons of individual MAb affinities between virus isolates to be
      made.

PMID- 7822841
TI  - Characterization of a monoclonal antibody to the capsule of Haemophilus
      influenzae type b, generated by in vitro immunization.
AB  - Monoclonal antibodies to polyribosylribitolphosphate (PRP), the capsular
      polysaccharide of Haemophilus influenzae type b (Hib), are useful tools in the
      investigation of the molecular and cellular mechanisms causing Hib meningitis. A
      better understanding of these mechanisms may lead to improved therapeutic
      strategies. A number of different in vivo immunization techniques in BALB/c mice
      were used, which did not however reveal detectable serum levels of antibodies to
      PRP. Therefore a modified in vitro immunization technique, originally established
      for in vitro immunization of human B lymphocytes, was used for this weak
      immunogen in mice. After 5 days of in vitro stimulation with purified PRP the
      splenic lymphocytes of BALB/c mice were fused with the mouse myeloma line P3-X63
      Ag8.653. One hybridoma produced an IgM antibody (12E7) which recognized the
      capsular polysaccharide in ELISA and specifically labelled all tested Hib strains
      in immune fluorescent microscopy. The blotted polysaccharide PRP was
      immunostained with monoclonal antibody 12E7. Preincubation of Hib with this
      antibody enhanced the oxygen radical metabolism of polymorphnuclear leucocytes in
      a chemiluminescence assay. There was no cross-reactivity with the supernatants of
      other Haemophilus influenzae serotypes and other bacterial species, as shown by
      counterimmunoelectrophoresis.

PMID- 7822843
TI  - Illness-disease-sickness--paradigm.

PMID- 7822842
TI  - Molecular analysis of T cell receptor V beta chain to detect leukemia cell
      clonality in patients by adaptor ligation-mediated polymerase chain reaction.
AB  - We have developed a simple and rapid method to analyze the clonality of leukemia
      cells. After three rounds of amplification by adaptor-ligation polymerase chain
      reaction (PCR), the cDNA is cut with AluI, HaeIII, RsaI, and Sau3AI, and analyzed
      by polyacrylamide gel electrophoresis. The size of the restriction fragments is
      compared to that of the published restriction fragments size each TCR-beta
      subfamily V region. The sensitivity of adaptor-ligation PCR restriction enzyme
      analysis (AL-PCR-REA) was 10(-4) MOLT-4 T-ALL cell population in the normal
      peripheral blood lymphocytes (PBL). Application of AL-PCR-REA to PBL and bone
      marrow (BM) cells from eight clinical leukemia samples indicated that a detection
      sensitivity was rather low, but revealed the clonality of all eight clinical
      samples. This AL-PCR-REA method can detect clonality without the need for either
      radioisotopes or sequencing procedures.

PMID- 7822844
TI  - Humoral immunity response in malignancies with special reference to the effect of
      radiotherapy.
AB  - In view of the variability in the findings recorded by different authors in the
      level of immunoglobulins in patients suffering from malignancies, a study on 34
      cases of six types of malignancies treated with radiotherapy (telecobalt and
      telecesium) was carried out to record the humoral response and also to compare
      the response during radiotherapy and after radiotherapy in these cases. Serum of
      20 age-matched normal volunteers served as normal control. The study recorded
      that the pretherapy levels of IgA and IgG were raised in most of the cases; but
      the IgM was decreased than that of the control level. This is probably due to the
      fact that the selective clones of cells producing different types of
      immunoglobulins are responding to the malignancies in different ways. The
      midtherapy level of all immunoglobulins showed the value lower than the
      pretherapy level, but recovery was observed in the post-therapy period with all
      immunoglobulins in all the cases irrespective of the histological types of
      malignancies. It was also apparent from this study that the post-therapy gain in
      the level of immunoglobulins over midtherapy level was more pronounced in cases
      having telecobalt therapy. Assessment of humoral response in 25 patients
      suffering from squamous cell carcinoma of different grades revealed that the
      midtherapy fall and subsequent post-therapy gain had no definite correlation with
      grading.

PMID- 7822845
TI  - Gynaecological neoplasms in postmenopausal women of Himachal Pradesh.
AB  - A controlled prospective study was conducted on 300 postmenopausal women
      attending the Kamla Nehru Hospital from November, 1990 to August, 1992. The
      incidence of gynaecological neoplasms was 31.3% in both the study group (300
      postmenopausal women) and the control group (300 premenopausal women). The
      incidence of malignant neoplasms was 24.6% in study group and 8.6% in control
      group. This difference was highly significant (p < 0.001). Carcinoma cervix (16%)
      was the commonest gynaecological malignancy followed by ovarian cancer (6%). The
      incidence of benign neoplasms was lower in the study group (6.6%) as compared to
      the control (22.6%).

PMID- 7822846
TI  - Infection in haematological malignancies.
AB  - Fifty-six febrile episodes in 30 haematological malignancy cases were evaluated.
      Of these episodes 60.7% were in leukaemia cases. Clinical evaluation and
      investigation suggested infection in 42 episodes (75%) of fever and in rest 14
      (25%) no identifiable cause could be found. Bacterial infection predominated with
      an incidence of 80.9% followed by fungal infection in 11.9% and parasitic
      infection in 7.1% of the febrile episodes. Gram-negative bacteria were more
      frequently isolated (22/34) than Gram-positive bacteria (12/34). Staph aureus was
      the commonest Gram-positive organism. Kl pneumoniae and Esch coli were the common
      Gram-negative pathogens. The commonest organisms were sensitive to cephalosporin
      and gentamicin. Incidence of fever due to infection was significantly higher (p <
      0.001) in patients with absolute neutropenia, in whom the mortality rate was
      significantly higher (p < 0.001).

PMID- 7822847
TI  - Hyperuricaemia and perinatal outcome in pregnancy induced hypertension.
AB  - The effect of hyperuricaemia on perinatal outcome was evaluated in 40
      primigravidae with pregnancy induced hypertension and 20 normotensive women in
      the 3rd trimester of pregnancy. Serum uric acid level was a better indicator than
      blood pressure as an index of foetal prognosis. Even severe hypertension without
      hyperuricaemia was associated with better prognosis for the foetus. Conversely
      when hypertension was mild and hyperuricaemia was severe, the prognosis for the
      foetus was poor. A rise in serum uric acid level > or = 5.5 mg% is associated
      with increased perinatal morbidity and mortality. Women in pregnancy induced
      hypertension group with serum uric acid level > or = 5.5 mg% had a higher
      incidence of intra-uterine growth retardation, low birthweight, and stillbirth
      making perinatal mortality rate of 200/1000 total births. The results of this
      study indicate that serum uric acid level > or = 5.5 mg% can reflect the
      perinatal outcome.

PMID- 7822848
TI  - Hepatic histology in chronic liver disease in hepatitis B surface antigen
      positive cases.
AB  - The spectrum of histological changes in needle biopsies of the liver tissue was
      analysed in 43 patients with chronic liver disease who were positive for
      hepatitis B surface antigen (HBsAg) in their sera. Majority of the patients were
      around 40 years and there was a male predominance. According to histopathological
      pattern, there were 18 (41.8%) cases of chronic active hepatitis, 16 (37.2%)
      cases of inactive cirrhosis, 3 (6.9%) cases of chronic persistent hepatitis and 2
      (4.7%) cases of chronic lobular hepatitis and hepatoma each. Two (4.7%) cases
      could not be exactly categorised into any particular histological entity. The
      inflammation, hepatic cell necrosis and fibrosis were more marked in cases of
      chronic active hepatitis without past history of jaundice. Micronodular cirrhosis
      was the most common histological pattern in the study. Shikata orcein stain for
      detection of HBsAg in the hepatocytes was positive in 8 (18.6%) cases only.

PMID- 7822849
TI  - A clinicopathological study of multidrug therapy in borderline tuberculoid
      leprosy.
AB  - A study was undertaken to evaluate the efficacy of multidrug therapy as per WHO
      recommendation in 50 fresh cases (46 males and 4 females) suffering from
      borderline tuberculoid leprosy. All were given multidrug therapy consisting of
      rifampicin 600 mg once a month and dapsone 100 mg daily for 6 months. At the end
      of 6 months all were evaluated clinically and histopathological examinations of
      the lesions were studied. The lesions were still active in 60% of patients
      clinically; 32% cases receiving multidrug therapy had shown marked improvement.
      Histologically lymphocytic infiltration in skin still persisted in all the slides
      examined and nerve infiltration was still present in 68% of cases at the end of 6
      months after receiving multidrug therapy. The study shows that treatment with
      multidrug regimen for 6 months may not be sufficient to treat borderline
      tuberculoid leprosy cases.

PMID- 7822850
TI  - Cytopathological study of bone tumours.
AB  - Fine needle aspiration biopsy is now widely used for detection of any
      pathological lesions like neoplasm, specific inflammation, cysts, etc. In a study
      of 22 cases, 17 (77.2%) were diagnosed by aspiration. Specific diagnosis was
      found in 59% cases and in 18.2% cases suggestive diagnosis was confirmed by
      histopathological examinations from biopsy materials. Like other investigative
      methods it is accurate and informative. It is also simple, can be done quickly
      and cheaper economically.

PMID- 7822851
TI  - Localised malignant mesothelioma of visceral pleura.

PMID- 7822852
TI  - Spondylo-epiphyseal dysplasia tarda with progressive arthropathy.

PMID- 7822853
TI  - Pemphigus in Goa.

PMID- 7822854
TI  - Current opinion in cardiopulmonary resuscitation.

PMID- 7822855
TI  - CPA and medical services: missing prerequisite.

PMID- 7822856
TI  - An easy method to remove self-retained Foley catheter.

PMID- 7822857
TI  - Quality circles in Medicare.

PMID- 7822858
TI  - Formation of autoantibodies, including anti-cytokine antibodies, is a hallmark of
      the immune response of early B cells.

PMID- 7822859
TI  - Novel autoantibodies in human diseases.

PMID- 7822860
TI  - Naturally occurring autoantibodies to interleukin-1 alpha, interleukin-6,
      interleukin-10, and interferon-alpha.

PMID- 7822861
TI  - Specific autoantibodies directed against interferon-alpha in pharmaceutically
      prepared human immunoglobulin preparations.

PMID- 7822862
TI  - Natural antibodies to interferon-gamma in humans: inhibition of the biological
      activity of IFN-gamma by human anti-IFN-gamma antibodies.

PMID- 7822863
TI  - Natural IgG autoantibodies in the sera of healthy individuals.

PMID- 7822864
TI  - Standardization of cytokines and their ligands.

PMID- 7822865
TI  - Human antibodies to recombinant factor VII in hemophiliacs.

PMID- 7822866
TI  - Porcine factor VIII in factor VIII antibody-positive hemophiliacs.

PMID- 7822867
TI  - Human antibodies to recombinant interleukin-2 in patients with hypernephroma.

PMID- 7822868
TI  - Induction of anti-granulocyte-macrophage colony-stimulating factor antibodies
      against exogenous nonglycosylated GM-CSF: biological implications.

PMID- 7822869
TI  - Human antibodies to insulin in diabetes.

PMID- 7822870
TI  - Distribution of interferon-alpha 2 genes in humans.

PMID- 7822871
TI  - Interferon antibodies in thrombocythemia.

PMID- 7822872
TI  - Recombinant interferon-alpha 2 antibodies in chronic lymphocytic leukemia.

PMID- 7822873
TI  - Recombinant interferon-alpha 2 antibodies in renal cell carcinoma. Delta-P Study
      Group.

PMID- 7822874
TI  - Different specificities of SLE-derived and therapy-induced interferon-alpha
      antibodies.

PMID- 7822875
TI  - Specificities of therapy-induced anti-interferon-alpha antibodies.

PMID- 7822876
TI  - Incidence and clinical significance of therapy-induced neutralizing antibodies
      against interferon-beta.

PMID- 7822877
TI  - Clinical relevance of recombinant interferon-alpha 2a antibodies in patients with
      hairy cell leukemia.

PMID- 7822878
TI  - Clinical significance of recombinant interferon-alpha 2 neutralizing antibodies
      in hepatitis patients.

PMID- 7822879
TI  - Autoimmunity and antibodies to interferons in patients with carcinoid tumors-
      clinical consequences.

PMID- 7822880
TI  - Roferon (rIFN-alpha 2a) is more immunogenic than intron A (rIFN-alpha 2b) in
      patients with chronic myelogenous leukemia.

PMID- 7822881
TI  - Topical capsaicin as an adjuvant analgesic.
AB  - Topical capsaicin has been studied in a variety of conditions by uncontrolled and
      controlled trials. It is attractive because it is a simple, safe treatment.
      Although these studies suggest an analgesic effect, even placebo-controlled
      trials have been impossible to blind due to the burning sensation induced by the
      capsaicin. A high placebo response rate in the controlled trials is an
      interesting observation and may account for the apparent salutary effect reported
      in the studies lacking a control. A careful scrutiny of the results of these
      trials to date as well as clinical experience indicate at best a modest effect
      with the currently available preparations with many patients failing to find
      relief, finding the relief unsatisfactory, or being unable to tolerate the
      burning sensation. Occasional patients appear to have a very good result, and
      these unusual cases may not be reflected by clinical trials. Topical capsaicin is
      generally not satisfactory as a sole therapy for chronic painful conditions,
      although it may serve as an adjuvant to other approaches.

PMID- 7822882
TI  - Centrally acting skeletal muscle relaxants and associated drugs.
AB  - A review of available studies supports a role for muscle relaxants in the
      treatment of painful musculoskeletal disorders. The utility of these drugs is
      limited by sedation and other side effects, as well as by the potential for abuse
      and dependency. Other drugs can also be used in the treatment of muscle spasm,
      specifically diazepam, baclofen, dantrolene sodium, and quinine sulfate. The
      pharmacology of the muscle relaxants and these other agents is discussed and
      practical suggestions for use are offered.

PMID- 7822883
TI  - Corticosteroids as adjuvant analgesics.
AB  - Corticosteroids have multiple effects as adjuvant drugs in pain management. Their
      pharmacologic characteristics will be described. Studies documenting the efficacy
      of corticosteroids for different pain syndromes and other cancer-related symptoms
      will be reviewed. Practical guidelines will be given and directions for future
      research suggested.

PMID- 7822884
TI  - The neuroleptics as adjuvant analgesics.
AB  - The role of neuroleptic drugs as adjuvant analgesics has been a subject of
      longstanding controversy. Despite frequent claims of efficacy, evidence from
      controlled trials supports neither claims of intrinsic analgesic properties nor
      the routine use of the neuroleptics as a means to reliably induce clinically
      useful analgesia. Methotrimeprazine is unique in that there is evidence for
      reliable dose-related analgesia that is comparable to opioid-mediated analgesia,
      although routine use is not recommended. Despite probable interaction with opioid
      receptors, there is insufficient evidence to support a role for the butyrophenone
      category of neuroleptics as adjuvant analgesics. Limited trials of the
      neuroleptics may be considered for pain that has been unresponsive to more
      conventional pharmacologic approaches, especially when associated with headache,
      nerve injury, or psychological distress. The neuroleptics have an important role
      in the symptomatic management of agitation, delirium, and nausea, particularly in
      patients with cancer.

PMID- 7822885
TI  - A retrospective study of risk factors of akathisia in terminally ill patients.
AB  - Akathisia is a distressing disorder that manifests as a state of restlessness and
      motor agitation. We aim to highlight the problem of akathisia to the palliative
      care physician by identifying and quantifying risk factors in the terminally ill.
      A retrospective case-control study was utilized to investigate risk factors for
      akathisia. Medical records of cases (N = 100) and controls (N = 365) archived in
      a computerized database were downloaded and risk factors determined using
      conditional logistic regression analyses. Exposure to pharmacologically similar
      drugs, such as haloperidol [odds ratio (OR), 18.4; 95% confidence interval (CI),
      8.2-41.4], prochlorperazine (OR, 8.1; 95% CI, 3.0-21.8), and promethazine (OR,
      3.3; 95% CI, 1.3-8.0), conferred an increased risk. Other significant variables
      were exposure to morphine (OR, 5.3; 95% CI, 1.9-14.2), sodium valproate (OR, 2.5;
      95% CI, 1.0-6.4), and sodium bicarbonate/tartrate (Ural) (OR, 4.2; 95% CI, 1.2
      15.3). Highlighting factors that predispose patients to akathisia emphasizes that
      this syndrome should not be forgotten when treating the terminally ill. It is
      recommended that those drugs identified should be judicially used and carefully
      monitored.

PMID- 7822886
TI  - Cold-pressor pain tolerance in opiate and cocaine abusers: correlates of drug
      type and use status.
AB  - The objective of this study was to describe pain tolerance in drug abusers.
      Research suggests that drug dependence and pain perception share common
      neuroanatomical and neurophysiological substrates; thus the abuse of psychoactive
      drugs was hypothesized to relate to pain tolerance. We examined cold-pressor pain
      tolerance in 122 male, current and former opioid and cocaine abusers, across use
      status and primary drug of abuse. Descriptive analyses showed that the ratio of
      pain-sensitive to pain-tolerant persons was considerably higher than that
      described in the normative cold-pressor pain literature. Two-way analysis of
      variance revealed a significant main effect for using status, indicating that
      current drug use is associated with decreased pain tolerance. The main effect for
      drug type approached significance, implying that persons who abuse opioids
      manifest less pain tolerance than cocaine users. The findings emphasize the
      importance of studying pain tolerance and drug abuse as interrelated phenomena.

PMID- 7822887
TI  - A probabilistic model for detecting coding regions in DNA sequences.
AB  - A probabilistic model is presented to predict whether or not an anonymous
      sequence of DNA contains exons. The method is shown to be at least as reliable as
      Grail, a well-known neural network solution to the problem, and to be
      significantly more amenable to customization for specific prediction problems.

PMID- 7822888
TI  - Balancing sexual partnerships in an age and activity stratified model of HIV
      transmission in heterosexual populations.
AB  - A mathematical model of the transmission dynamics of HIV-1 in a heterosexual
      population stratified by age, sex, and sexual activity (defined by rates of
      sexual partner acquisition) is presented. The model represents an extension of
      previous studies with a special focus on patterns of mixing or contact between
      sexual activity and different age classes of the two sexes. A range of mixing
      patterns between these groups is specified for both sexes. Mixing is described on
      two scales from fully assortative to fully disassortative, with random defined
      either according to numbers of sexual partnerships or numbers of people. The
      sexual partnerships in the model are balanced by changes in the rates of sexual
      partner acquisition between particular groups and a range of changes, from only
      women changing behaviour to only men changing behaviour, are analysed. The
      pattern of mixing is most influential in determining the shape and magnitude of
      the epidemic, but the manner in which people choose partners (i.e. dependent on
      numbers or proportions in the population) is also important. The relative
      importance of variation in transmission probabilities and mean rates of partner
      change on the course of the HIV epidemic is also illustrated. The analysis of the
      sensitivity of predictions to changing parameters in the force of infection term
      of the model provides a theoretical basis from which the influence of control
      strategies and the demographic effects of HIV can be analysed.

PMID- 7822889
TI  - Sodium ion transport in the intestinal wall: a mathematical model.
AB  - A theoretical approach to study the uptake of sodium ions across the
      gastrointestinal mucosa and the concentrations at which they are taken up into
      the underlying blood capillaries has been attempted. A two-phase model of the
      mucosa is considered, consisting of an extracellular phase and a cellular phase.
      The model takes into account two important modes of transport: diffusion under
      concentration gradient and potential gradient (electrodiffusion) and active
      transport which is ATPase enzyme mediated. Appropriate partial differential
      equations for the two mechanisms of transport are derived and are solved by
      iterative methods. An approximate distance from the lumen where the capillaries
      lie is somewhere between 10 and 15% of the total wall length. The mean
      concentration of sodium ions made available for absorption at the capillaries is
      studied with time. A functional form for the variation of potential with respect
      to distance is proposed, and by comparing model solutions with experimental data
      it is calculated explicitly.

PMID- 7822890
TI  - Stochastic models for geriatric in-patient behaviour.
AB  - Departments of geriatric medicine engage in two distinct forms of clinical
      activity: acute/rehabilitative and long-stay care. These are organizationally
      distinct and have very different resource needs. Current hospital planning
      models, however, assume that patients all move through the system at the same
      rate, thereby ignoring this effect of inherent heterogeneity in patient
      behaviour. The present paper describes the movement of patients through geriatric
      hospitals by a two-stage continuous-time Markov model, where the stages represent
      acute/rehabilitative and long-stay patients respectively. Patients are initially
      admitted to the first stage, from which they may depart from the system, by death
      or discharge, or move into the second stage, from which they eventually depart by
      death or discharge (unlikely). Admissions are modelled in two ways: either as
      replacements for departures or as a Poisson stream. Expressions for the
      distribution and movement of numbers of patients are derived and evaluated for
      data from a number of hospitals. Such an approach has the advantage, over
      previous crude models, of taking into account different types of patients and
      introducing variability, thus making it possible to extract variances as well as
      means of numbers of geriatric patients requiring hospital care.

PMID- 7822891
TI  - Non-invasive pressure measurement in arterial disease.

PMID- 7822892
TI  - For how long should carotid endarterectomy surveillance be continued?
AB  - Early restenosis represent the most important and more common failure after
      carotid endarterectomy. For this reason, after its first description made in 1976
      by Stoney and String, it raised general interest among vascular surgeons. In
      spite of the efforts to clear the causes of this phenomenon, none of the numerous
      papers published in the literature has defined a specific cause determining
      restenosis. Nevertheless, at present, this hyperplastic response of the arterial
      wall to trauma after operation is generally considered benign because it is
      rarely responsible for new neurological symptoms or early internal carotid artery
      occlusion. This unanimous conviction has been achieved after years of
      instrumental and clinical postoperative follow-up performed all over the world.
      At the same time and probably for these reasons, recently, a new discussion has
      begun about the usefulness and cost-effectiveness of prolonged Duplex scanning
      postoperative surveillance of the endarterectomized carotid arteries. This new
      question raised our curiosity in verifying the validity of this new approach, so
      we reviewed accurately our laboratory follow-up registry and the data regarding
      onset, evolution and clinical outcome of early restenosis. These data associated
      with a meticulous review of the experience of other authors convinced us that the
      patients operated on, need, in most cases, a short even aggressive period of
      careful follow-up (generally the first six months).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7822893
TI  - Arterial aneurysms in Behcet's disease.
AB  - Six cases of arterial aneurysms, due to "Behcet's disease" located in various
      arteries are presented. Surgical reconstruction included: Resection of the
      lesions and replacement with corresponding grafts with satisfactory results. In
      spite of the macroscopic similarity of the aneurysms found in "Behcet's disease"
      as compared to those of mycotic origin, the presence of any microorganism could
      not be detected in various cultures or pathological specimens. Meticulous
      diagnosis on the nature of the aneurysm, close follow-up and careful
      postoperative anticoagulant treatment, is imperative for satisfactory immediate
      and late results.

PMID- 7822894
TI  - Diminished platelet yield and enhanced platelet aggregability in platelet-rich
      plasma of peripheral vascular disease patients.
AB  - Centrifugation of citrated whole blood (cit-WB) for platelet rich plasma (PRP)
      preparation resulted in a significantly diminished platelet yield compared to
      when blood was collected in citrate + aspirin (acetylsalicylic acid; ASA) or EDTA
      anticoagulants in both apparently healthy young subjects and peripheral vascular
      disease (PVD) patients. The loss in platelets was significantly greater in PVD
      patients than in young apparently healthy subjects when using cit-WB. Median
      platelet volume (MePV) of PRP preparations was not different between PVD patients
      and apparently healthy subjects. The MePV of EDTA-PRP preparations was
      significantly bigger than cit-PRP and cit + ASA-PRP in both PVD patients and
      apparently healthy subjects. Citrate and citrate + ASA-PRP of patients was
      significantly more aggregable to adrenaline. In EDTA-PRP, adrenaline-induced
      aggregation did not occur. These findings indicate that platelet hyperactivity
      occurs in PVD even in the presence of ASA. Furthermore, studies involving the use
      of PRP may not be representative in PVD due to the significant loss of platelets
      during centrifugation. The methodology described here can be used by those who do
      not have facilities designed specifically for platelet research.

PMID- 7822895
TI  - Carotid atherosclerosis: echographic patterns versus histological findings.
AB  - The study was carried out on 25 whole carotid arteries explanted from a corpse
      and perfused at constant pressure to reproduce the conditions of an in vivo
      examination as much as possible. Out of 5 samples with intimal thickening
      detected by echo, fibrosis of the tunica media was observed by the pathologist in
      4 and microcalcification in 1. In 4 vessels with soft plaques at echo scanning, a
      wide necrotic area (2 cases), slack connective tissue (1 case) and cystic lesions
      (1 case) were observed. Hard lesions with (5 cases) or without (2 cases) a cone
      of shadow at echo evaluation corresponded to fibrous (2 cases) or fibrocalcific
      (3 cases) plaques. The histological study of the two echo-diagnosed thrombi
      showed an intermediate echographic pattern and the main feature of the non
      occluding thrombus was the absence of a lumen-lesion interface. Mixed plaques
      were diagnosed at echo in 9 arteries and the correspondent histological aspect
      was a typical atheromatous lesion in all cases. Thus, the comparison of the
      ultrasound image with the histological findings proved the reliability of
      echography in the detection of atheromatous lesions with an excellent agreement
      between the results at the 2 examinations. Since the type of carotid lesions has
      an impact upon clinical events these results might support the use of vascular
      ultrasound images in clinical applications.

PMID- 7822896
TI  - Toe systolic blood pressure after local cooling in primary Raynaud's phenomenon.
AB  - First toe systolic blood pressures (FTSBP) before and after first toe cooling
      were measured with the laser Doppler method in 17 normal women and 10 female
      patients with primary Raynaud's phenomenon (PRP). The room temperature was
      maintained at 26 degrees C. There was no significant difference in toe-arm
      systolic blood pressure ratio between the two groups. After toe cooling at 10
      degrees C, the PRP group had a significantly greater reduction in FTSBP than the
      normal group. Measurement of FTSBP before and after toe cooling is a useful
      method for assessing Raynaud's phenomenon in the toes of patients with PRP.

PMID- 7822897
TI  - External banding valvuloplasty of the superficial femoral vein in the treatment
      of primary deep valvular incompetence.
AB  - Primary deep venous insufficiency (PDVI) represents an important cause of chronic
      venous insufficiency (CVI). The clinical picture is generally related to a
      congenital weakness of the vein wall at the level of the valvular ring which may
      dilate its diameter with consequent lengthening and prolapse of the valvular
      cusps. However, in an initial stage of PDVI the leaflets are normally formed and
      may undergo restorative surgery. In this condition an external banding
      valvuloplasty (EBV) with a Dacron sleeve around the incompetent valve may restore
      the competence. The authors report 54 cases of superficial femoral vein EBV
      performed over a period of 1986 to 1991. The patients were affected by signs of
      CVI and/or relapsing, complicated or atypical varices in which descending
      venography showed a grade II, III or IV primary deep reflux. In a mean follow-up
      of 38 months (4 to 63 months) deep reflux had disappeared in 41 patients (76%),
      had significantly decreased in 8 (14.8%) and was completely unmodified in 5
      (9.2%). According to the experience of other authors, these results suggest the
      therapeutic validity of EBV in the initial stage of PDVI.

PMID- 7822898
TI  - Apo-lipoprotein profile in subjects with extracranial carotid atherosclerosis.
AB  - Relationships between plasma lipoproteins and cerebrovascular atherosclerosis are
      not completely clear. In a group of asymptomatic nondiabetic normolipidemic
      subjects, plasma lipid and apolipoprotein profiles have been related to
      extracranial carotid atherosclerotic lesions, as assessed by B-mode
      ultrasonography and independent relations between lipid and clinical parameters
      and carotid atherosclerosis have been evaluated. We have found that subjects with
      atherosclerotic lesions (both intimal thickening or plaque) had TG levels and
      CHO/HDL-C and LDL-C/HDL-C ratios significantly higher and HDL-C and apo A-I
      levels significantly lower in comparison with subjects with normal arteries. When
      patients were divided according to the lesions of carotid arteries subjects with
      atherosclerotic plaque presented HDL-C and apo A-I levels significantly reduced
      and TG and apo B levels and CHO/HDL-C and LDL-C/HDL-C ratios significantly
      increased in comparison with subjects with normal arteries, and HDL-C levels
      reduced and CHO/HDL-C and LDL-C/HDL-C ratios increased in comparison with
      subjects with intimal thickening. Patients with intimal thickening and normal
      subjects differed for HDL-C and TG levels and CHO/HDL-C and LDL-C/HDL-C ratios.
      At multivariate analysis HDL-C levels (negatively), age, hypertension and
      cigarette smoking (positively) resulted independently associated with
      cerebrovascular atherosclerosis. Our data seem to show that, although several
      lipid and apoprotein abnormalities are able to initiate the atherosclerotic
      process in extracranial carotid district, probably the presence of low HDL
      cholesterol levels is an important condition to determine the further worsening
      of the lesions.

PMID- 7822899
TI  - The prevalence of peripheral vascular disease in type 2 diabetic patients with
      and without proteinuria.
AB  - It has been reported that albumin excretion rate may reflect not only an
      indication of renal disease but also a widespread vascular damage. We studied the
      relationship between overnight albumin excretion rate (AER) and peripheral
      vascular disease (PVD), using Doppler ultrasound, and its major risk factors in
      80 Type 2 (non-insulin-dependent) diabetic patients. Thirty-eight of these
      patients had normoalbuminuria (AER < 30 micrograms/min), 22 had microalbuminuria
      (30-200 micrograms/min) and 20 had macroalbuminuria (> 200 micrograms/min).
      Patients with macroalbuminuria were older than those with normoalbuminuria (p <
      0.01) and they also had a longer duration of diabetes (p < 0.05). Patients with
      elevated albumin excretion rates had elevated prevalence of PVD (macroalbuminuric
      40%, p < 0.01; microalbuminuric 27.2%, p < 0.05; vs normoalbuminuric 7.8%). Among
      the risk factors analysed, hypertension and triglyceride concentrations were
      higher in the proteinuric diabetics (macroalbuminuric p < 0.001, p < 0.01;
      microalbuminuric p = NS, p < 0.01 respectively), while HDL-C levels were found to
      be significantly lower in this group (p < 0.05). In the diabetic group as a
      whole, raised AER was correlated with PVD (p < 0.05), duration of diabetes and
      systolic blood pressure (p < 0.01). We conclude that the prevalence of PVD was
      significantly higher in Type 2 diabetic patients with elevated albumin excretion
      rate. Furthermore, these patients had higher blood pressure and low HDL-C.

PMID- 7822900
TI  - Prevalence of peripheral arterial occlusive disease and associated risk factors
      in a sample of southern Sardinian population.
AB  - We studied a sample of adult population over 20 years old of Donori (totally 2049
      inhabitants), a small town near Cagliari, South Sardinia, to: (1) Evaluate the
      prevalence of peripheral arterial occlusive disease of lower limbs (PAOD)
      diagnosed by standard questionnaire and US CW Doppler examination and associated
      risk factors in South Sardinia. (2) Compare the reliability of these two
      diagnostic methods. Our study included the answers to a standard anamnestic
      questionnaire (according to the WHO recommendations), physical examination and CW
      Doppler study of the lower limb arteries, the determination of the arterial
      systolic and diastolic pressure, ankle/arm pressure ratio, Body Mass Index, blood
      glucose, total and HDL-cholesterol, triglycerides and fibrinogen (the
      hematochemical examination only on 50% of the sample). The surveyed sample was of
      577 subjects (37.96% of 1520, the eligible subjects over 20 years old), 237 males
      and 340 females. An arteriopathy was diagnosed by means of CW Doppler in 27
      subjects, 20 M and 7 F. The overall prevalence of PAOD was 4.67% of the sample
      (2.06% of females, 8.43% of males). Prevalence steadily increased with age, and,
      surprisingly, the disease was not absent in young people (2 cases within males
      with age < or = 40 years). Conversely only 18.5% of PAOD patients were
      symptomatic. The overall prevalence of associated risk factors was: diabetes
      3.6%, hypercholesterolaemia 59.1%, smoking 21.3%, arterial hypertension 21.6%,
      obesity 17.9%, hypertriglyceridaemia 9.3%, hyperfibrinogenaemia 4.67%. Among the
      males a significant correlation has been found, among the values of BMI vs age
      and total cholesterol, age vs total cholesterol, systolic blood pressure,
      diastolic pressure, fibrinogenaemia. Among the females, the systolic and
      diastolic pressure, BMI, total cholesterol, LDL-cholesterol, triglycerides and
      fibrinogen are significantly correlated with age; BMI correlates with systolic
      and diastolic blood pressure, fibrinogen; a nearly significant correlation has
      been found between BMI and triglycerides.

PMID- 7822901
TI  - The effect of mannitol on reperfusion after severe induced subtotal ischemia of
      the leg. A hemodynamic, biochemical and metabolic study in a pig hind limb model.
AB  - Revascularization of acutely ischemic muscle tissue is followed by edema,
      decreased oxygen utilization, increased vascular resistance and massive efflux of
      intracellular compounds indicating loss of cellular integrity, with resultant
      irreversible damage. In this pig hindlimb study, 8 pigs were submitted to
      standardized subtotal ischemia of one leg and mannitol was administered i.v.
      prior to and during 2.5 hours of reperfusion. Compared to 9 controls, the
      mannitol treated pigs had increased blood flow to the legs, increased oxygen
      consumption and decreased release of intracellular compounds (CK). This indicates
      that mannitol attenuates the ischemia/reperfusion syndrome. Muscle energy
      metabolic parameters showed a similar response to ischemia for both mannitol
      treated pigs and controls and no differences in recovery were detected during 2.5
      hours of reperfusion between the groups.

PMID- 7822902
TI  - The use of medicinal leeches, Hirudo medicinalis, to restore venous circulation
      in trauma and reconstructive microsurgery.
AB  - Following replantation of complete or incomplete nonviable amputations of digits
      and hands, as well as microsurgical free tissue transfer, there is often a
      critical need for adjuvant therapy in order to restore sufficient venous
      drainage. In 24 out of 29 patients, venous insufficiency was successfully treated
      with the use of medicinal leeches. In a group of patients who had undergone
      replantation procedures (11 patients total), 9 patients (8 with digit and 1 with
      hand amputations) had venous drainage successfully restored with medicinal
      leeches, while in a group of patients who had free tissue transfers (18 patients
      total), 15 had the venous congestion treated successfully with leeches. The
      results indicate that medicinal leeches are a valuable, alternative method for
      the treatment of venous congestion in both replantation patients and those who
      have undergone free tissue transfer.

PMID- 7822903
TI  - The effect of hydroxyethylrutosides on capillary filtration in moderate venous
      hypertension: a double blind study.
AB  - The aim of this study was to evaluate the effect of hydroxyethylrutosides on
      capillary filtration in subjects with mild to moderate venous incompetence-
      superficial varicose veins and/or deep venous disease and ankle oedema--using the
      vacuum suction chamber (VSC) device applied to the internal perimalleolar region
      and the wheal vanishing (WV) time. Subjects entered in to the study were
      randomised to receive either hydroxyethylrutosides (1 g twice daily for 4 weeks)
      or placebo for four weeks. The two groups entering and completing the study were
      comparable. Microcirculatory parameters (laser-Doppler resting flux, the
      venoarteriolar response, transcutaneous PO2 and PCO2) remained constant during
      the four week study in both groups. The WV time, which was comparable in the two
      groups at the beginning of the study decreased significantly [from a median 55
      min (interquartile 955 min), to a median 45 minutes (interquartile 65-40 min) in
      the treated group, p < 0.01]. No change was observed in the WV time in the
      placebo group. Subjective symptoms measured with an analogue scale improved
      following treatment with hydroxyethylrutosides [foot oedema (p < 0.005), ankle
      oedema (p < 0.001), and paraesthesia (p < 0.01)]; only night cramps were reported
      less in patients receiving the placebo (p < 0.05). In conclusion, the WV time can
      be used to assess the beneficial effect of therapy on capillary filtration in
      subjects with mild-moderate venous hypertension, even after a short period of
      treatment, and before other microcirculatory parameters change. Furthermore, the
      changes observed in WV time correlate well with an improvement in patients
      symptoms.

PMID- 7822904
TI  - Epidemiology of varicose veins. A review.
AB  - Disease of the venous system is a major problem affecting western societies,
      resulting in considerable morbidity in the population and cost to the health
      service. In many countries "varicose veins are probably the commonest disorder
      presenting to general surgeons" and an average of 30% of district nursing time is
      estimated to be spent caring for patients with venous ulcers. For the patient
      with varicose veins or leg ulceration, there is often persistent discomfort and
      disability extending over long periods of time. Despite this, little
      epidemiological research has been carried out on venous disease, perhaps partly
      because of society's perception that venous disease is not a major problem and it
      is not normally a cause death. More recently however, efforts have been made to
      conduct structured epidemiological studies to identify risk factors and to
      clarify the geographical variations suggested in the past by anecdotal evidence.
      This article reviews recent epidemiological studies, discusses the prevalence of
      varicose veins and presents evidence for and against the differing theories of
      causation.

PMID- 7822905
TI  - Atheromatous embolization precipitated by oral anticoagulants.
AB  - Five patients with a "blue or purple" toe syndrome due to atheromatous
      embolization probably precipitated by oral anticoagulant therapy are reported. In
      four, the symptoms started a few weeks after initiation of oral anticoagulants
      and in the fifth they were clearly aggravated by coumarinic drugs. Prior to
      anticoagulation, one patient had received a course of thrombolytic therapy and
      two had undergone an arterial catherization without embolic events. A diagnostic
      arteriography performed in four patients caused no new symptoms. All patients had
      advanced atherosclerosis. A shaggy aorta and/or pelvic arteries were found in
      four and in the fifth a highly stenotic femoral lesion appeared the source of
      peripheral embolization. Oral anticoagulants were interrupted in all five and
      four underwent reconstructive vascular surgery to eradicate the nidus of
      atheromatous emboli. One died postoperatively from multiple organ failure. The
      poor condition of the fifth patient precluded aorto-iliac surgery. No new
      episodes of embolization occurred and the symptoms disappeared, although one
      patient needed a toe amputation for a skin lesion that had proceeded to gangrene.
      The possible role of anticoagulant drugs in precipitating atheromatous
      embolization is discussed and the importance of recognizing the syndrome is
      emphasized.

PMID- 7822906
TI  - The endoscopic diagnosis and possible treatment of nerve root avulsions in the
      management of brachial plexus injuries.
AB  - The spinal cord, dorsal rootlets, and ventral rootlets at the cervical level were
      visualized by endoscopy in ten goats. It is currently possible to visualize and
      document avulsed rootlets. With refinement in techniques and instruments, it will
      be possible to perform repairs, transfers or implantation of avulsed rootlets in
      the brachial plexus.

PMID- 7822907
TI  - A burn caused by the operating microscope light during brachial plexus
      reconstruction.
AB  - A case of an accidental burn caused by the operating microscope light during
      brachial plexus reconstruction is reported along with the various factors which
      could lead to such an injury.

PMID- 7822909
TI  - Internal splints for prevention of first web contracture following severe
      disruption of the first web space.
AB  - Different internal spring-splint configurations were examined to determine the
      most effective in preventing adduction contracture after severe injuries
      disrupting the first web space.

PMID- 7822908
TI  - A comparative study of the heterodigital neurovascular island flap in thumb
      reconstruction, with and without nerve reconnection.
AB  - 41 heterodigital neurovascular island flaps were used to cover defects of the
      tactile pad of the thumb in 17 years. With an average follow-up of 75.5 months,
      30 patients were reviewed. 17 were treated by the original Littler technique and
      13 were treated with the same flap reconstruction but with division of the
      digital nerve innervating the flap and re-anastomosis of this nerve to the
      proximal nerve end of the ulnar digital nerve of the thumb. Good aesthetic and
      functional results were achieved in both groups. Sensory acuity did not appear to
      decrease with time. The nerve reconnection technique solves the "double
      sensibility" phenomenon (present in 41.1% of our cases treated by the original
      technique), but two-point discrimination is less than that achieved by the
      Littler technique. Most complaints were related to the donor site such as
      hypertrophic scarring or scar contracture and cold intolerance, but these did not
      cause any real functional impairment.

PMID- 7822910
TI  - Repair of acute scapho-lunate dissociation facilitated by the "TAG" suture
      anchor.
AB  - A case of acute scapho-lunate dissociation is described in which the operative
      treatment was facilitated by the use of the "TAG" suture anchor.

PMID- 7822911
TI  - Frayed ulno-triquetral and ulno-lunate ligaments as an arthroscopic sign of
      longstanding triquetro-lunate ligament rupture.
AB  - In patients with chronic wrist pain of more than 6 months duration, arthroscopy
      may reveal fraying of the ulno-triquetral and ulno-lunate ligaments. This can be
      a sign of longstanding triquetrolunate dissociation. We present a prospective
      study in which frayed ulno-triquetral (UT) and ulno-lunate (UL) ligaments were
      sought on wrist arthroscopy and correlated with longstanding triquetro-lunate
      (TL) rupture.

PMID- 7822912
TI  - Incidence of cartilaginous and ligamentous lesions of the radio-carpal and distal
      radio-ulnar joint in an elderly population.
AB  - 51 wrists of 30 embalmed cadavers have been used to perform an anatomical and
      radiological study relating cartilaginous and ligamentous lesions of the wrist
      with sex, age, ulnar variance (UV) and the state of the triangular fibrocartilage
      complex (TFCC) in an elderly population (mean 76.6 years). Two-thirds of all
      wrists (66%) showed cartilaginous lesions, mainly on the lunate (22, or 44%). The
      TFCC was perforated in 23 wrists (46%), and most were central degenerative
      perforations. Correlations were found between ulnar variance and TFCC thickness
      (P < 0.05) and ulnar variance and TFCC perforations (P < 0.05). A significant
      relation was observed between age and proximal row intercarpal ligamentous
      ruptures (P < 0.05) and between age and ulnar variance (P < 0.05). No statistical
      correlation was seen between ulnar variance and cartilaginous lesions on the
      lunate (P < 0.05) in this slightly ulnar negative population (mean-0.37 mm).

PMID- 7822913
TI  - Traumatic dislocations of the distal carpal row.
AB  - 13 patients who sustained high-energy crush or blast injury of the carpal bones
      were reviewed after a mean follow-up period of 30 months. These complex injuries
      resulted in unusual disruptions of the distal carpal row and adjacent
      metacarpals. Frequent involvement of the carpometacarpal (CM) joints and
      violation of the proximal carpal row were also demonstrated. Nine were open
      injuries, with the majority accompanied by significant soft tissue damage.
      Treatment included either closed reduction or open reduction and Kirschner wire
      fixation, and soft tissue procedures as indicated. In this series, the majority
      of the open injuries gave unfavourable functional results despite adequate carpal
      alignment. Several cases had disastrous outcomes related to associated vascular
      injuries. Closed injuries, on the contrary, followed a relatively benign course.
      Nevertheless, decreased grip strength persisted in both groups for a long time.
      Patients with such a complex carpal injury should expect a less favourable
      prognosis due to the severe nature of the trauma.

PMID- 7822914
TI  - Chip fractures of the triquetrum. Mechanism, classification and results.
AB  - Of 231 patients with fractures of the triquetrum, 65 were followed up after a
      mean period of 46.8 months. The fractures were classified and radiological and
      clinical follow-up was carried out. Pathomechanical aspects of the origin of the
      fracture were also considered. It appears that the chisel action of the dorso
      proximal edge of the hamate striking against the fully extended and ulnar
      deviated wrist is the major cause of the dorsal chip fracture of the triquetrum.
      Conservative therapy involving immobilization of the injured wrist for 3 weeks
      proved to be successful. If the bone fragment healed, it took 6 to 8 weeks. There
      was no indication for surgical intervention. We found no signs of post-traumatic
      instability of the joint. There was good vascularization of the bone, which
      excluded the possibility of avascular necrosis. All fractures involving the main
      body of the triquetrum united.

PMID- 7822915
TI  - Distal radial osteotomy for malunion of wrist fractures in young patients.
AB  - Malunion after a fracture of the distal radius in a young patient causes a
      significant disturbance of wrist function. We have performed distal radial
      osteotomies in 11 patients to correct radial malunion. Surgery was indicated in
      young patients with functional disability in the wrist due to limited wrist
      motion and pain. Many had an unacceptable cosmetic appearance of the wrist. In
      all patients surgery consisted of opening wedge osteotomies to correct radial
      tilt and radial angle. In some instances it was not possible completely to
      restore radial length without a reduction in ulnar length. Post-operatively
      combined dorsal and volar flexion improved from a mean of 34 degrees to 72
      degrees. Combined pronation and supination improved from a mean of 68 degrees to
      106 degrees. Pain assessed on a simple four-point functional score was decreased
      from a mean of 3.3 to 1.3.

PMID- 7822916
TI  - Remodelling of a displaced phalangeal neck fracture.
AB  - Phalangeal neck fractures are uncommon in children. When these injuries to the
      proximal and middle phalanges are displaced and not treated operatively the
      fracture may heal in a malunited position with loss of motion at the IP joint.
      Remodelling in the area of the phalangeal neck is thought to be reduced because
      of its distance from the physis. In cases of malunion osteotomy of the phalangeal
      neck may be required to restore anatomy and motion. A case is described which
      demonstrates complete remodelling of a displaced middle phalangeal neck fracture
      in a child and recovery of a normal range of motion without operative
      intervention.

PMID- 7822917
TI  - Initial treatment of closed metacarpal fractures. A controlled comparison of
      compression glove and splintage.
AB  - A prospective clinical trial compared two forms of initial management for closed
      stable fractures of the shaft of the finger metacarpals. Patients were randomized
      to treatment with a compression glove and early mobilization (21 patients) or to
      immobilization in a plaster splint (21 patients). The mean loss of total active
      flexion (MP+PIP+DIP) in the second week after injury was 56 degrees in the glove
      group and 84 degrees in the splint group (P = 0.0036). In the third week, the
      mean loss of flexion was 23 degrees and 46 degrees respectively (P = 0.0010).
      Hand volume and PIP joint circumference were significantly smaller in the glove
      group in the second week but not in the third and fourth weeks. Within each
      group, however, there was no correlation between range of motion and swelling,
      suggesting that these were independent variables in this study. The support of
      the glove helped to relieve pain. Use of a compression glove avoided the loss of
      function imposed by splintage and was associated with a greater range of movement
      during the second and third weeks.

PMID- 7822918
TI  - Rolling belt injuries in children.
AB  - The rolling belts on agricultural machinery attract children who unconsciously
      grab them. The injuries produced include friction burns, injuries to flexor
      tendons, digital nerves and arteries, skin in zone 2 and fractures. Subtotal or
      total amputation may occur. We present the results of such injuries to 44 fingers
      in 16 children aged 1 to 9. The functional results are not satisfactory. In order
      to grade the results we have devised a classification to this injury. The
      survival rate for all fingers was 71%, but in the fingers with circulatory
      problems the survival rate was 50%. On functional assessment seven patients had a
      good result, seven moderate, and two fair.

PMID- 7822919
TI  - Sellotape ischaemic injury to the fingertip.
AB  - A case is reported of significant ischaemic damage to a fingertip from the use of
      Sellotape. The elasticity of Sellotape has been tested and compared with that of
      Elastoplast, illustrating the stiffness of Sellotape and thus emphasizing its
      unsuitability. The general public needs to be aware of the dangers of using non
      proprietary dressings and the medical profession must remain vigilant about the
      elasticity of dressings.

PMID- 7822920
TI  - The rupture rate of acute flexor tendon repairs mobilized by the controlled
      active motion regimen.
AB  - A series of 233 patients with complete divisions of flexor tendons in zones 1 and
      2 underwent operation following emergency admission over a period of 3.5 years.
      These included 203 patients with 317 divided tendons in 224 fingers injuries in
      zones 1 and 2 and 30 patients with 30 complete divisions of the flexor pollicis
      longus tendon in zones 1 and 2. All of these patients were mobilized post
      operatively in a controlled active motion regimen. 13 (5.8%) fingers and five
      (16.6%) thumbs suffered tendon rupture during the post-operative period. Patients
      treated during the last year of the study were followed prospectively for a
      minimum period of 3 months; ten of the 16 (62.5%) fingers with zone 1 repairs, 50
      of the 63 (79.4%) fingers with zone 2 repairs, all three (100%) FPL divisions in
      zone 1 and three of four (75%) FPL divisions in zone 2 had good and excellent
      results on assessment by the original Strickland criteria (Strickland and
      Glogovac, 1980). These results confirm the safety of this regimen as an
      alternative to other regimens of post-operative flexor tendon repair mobilization
      in zone 1 and 2 finger injuries. However, in the unmodified form used in this
      series, this regimen has too high a rupture rate for FPL mobilization.

PMID- 7822921
TI  - Type 4 median nerve entrapment after elbow dislocation.
AB  - A rare case of median nerve entrapment after posterior elbow dislocation is
      reported. Nerve entrapment was both in the healed medial epicondyle fracture and
      within the elbow joint and we recommend placing this type of entrapment
      separately in an extended classification of median nerve entrapment following
      elbow dislocation.

PMID- 7822922
TI  - Bifid median nerve compression due to a musculotendinous anomaly of FDS to the
      middle finger.
AB  - A case is presented of a bifid median nerve whose longest portion had a normal
      course while the other portion passed through a hole in the FDS tendon of the
      middle finger, at its musculotendinous junction. This caused nerve compression
      during muscle contraction, producing pain and dysaesthesia in the middle finger
      suggesting carpal tunnel syndrome.

PMID- 7822923
TI  - Comparison of proximal and distal one portal entry techniques for endoscopic
      carpal tunnel release. A cadaver study.
AB  - Reported complications of endoscopic carpal tunnel release have increased as more
      surgeons use this technique to release the flexor retinaculum. We used a cadaver
      model to compare the results of endoscopic carpal tunnel release through a one
      portal distal (Group A, 15 specimens) and a one-portal proximal (Group B, 15
      specimens) entry site with a new endoscopic technique. Our custom-made glass tube
      of three different sizes (5, 7, and 9 mm in diameter) is designed to house an
      endoscope and accommodate a meniscus knife for releasing the flexor retinaculum.
      Complete release of the flexor retinaculum was obtained in all limbs in both
      groups. In Group A the one complication (7%) was loss of the cotton tip from the
      cotton swab stick within the carpal tunnel. In Group B, there was a single case
      of injury to the superficial palmar arch in one hand and breakage of a glass tube
      in another hand, for a total complication rate of 13%. No other damage to
      anatomical structures was noted.

PMID- 7822924
TI  - Factors associated with poor outcome following primary carpal tunnel release in
      non-diabetic patients.
AB  - A retrospective study was performed of 112 non-diabetic patients (133 hands) who
      had open surgical treatment for carpal tunnel syndrome, to determine the factors
      associated with poor outcome. None of the patients had a previous carpal tunnel
      release and all had a positive nerve conduction study to confirm the clinical
      diagnosis of carpal tunnel syndrome. Outcome was assessed at least 18 months
      after surgery and classified as excellent, good or poor. Outcome was deemed poor
      when symptoms were minimally improved, unchanged or worse after surgery. This
      occurred in 13.5% of treated hands. There was a higher chance of poor outcome in
      patients with physically strenuous work activities. All these heavy or repetitive
      manual workers were also involved in compensation and their poor outcome
      correlated with their inability to return to their original work. Other
      predisposing factors, associated hand conditions, duration of symptoms prior to
      surgery, the presence of bilateral or nocturnal symptoms, and the severity of the
      pre-operative nerve conduction deficit did not affect the final outcome after
      surgery.

PMID- 7822925
TI  - Outcome of carpal tunnel release in diabetic patients.
AB  - A retrospective study of 15 diabetic patients (20 hands), who underwent carpal
      tunnel release, was performed to determine the outcome. All patients had a
      minimum of 18 months of follow-up. Outcome was considered excellent if there was
      complete resolution of symptoms and this occurred in 35% of the treated hands.
      Eight hands (40%) had a good outcome with significant improvement of pre
      operative symptoms. Outcome was considered poor when symptoms were minimally
      improved, unchanged, or worse after surgery and this occurred in 25% of treated
      hands. All hands with a poor final result had either no electrodiagnostic
      evidence of localized compression or only mild compression in pre-operative nerve
      conduction studies. It was postulated that the contribution of localized
      compression to pre-operative hand symptoms was less than the contribution of
      peripheral neuropathy in these hands.

PMID- 7822926
TI  - Cystic radio-lucency of carpal bones in haemodialysis patients. An early
      indicator of the onset of carpal tunnel syndrome.
AB  - Patients receiving haemodialysis for more than 10 years were selected for this
      study in order to clarify an apparent sequential association of cystic lesions of
      carpal bones and carpal tunnel syndrome. X-rays and computed tomographs of 138
      hands of 69 patients revealed cystic radiolucency of carpal bones in 35% of the
      hands. Radiographs were classified into three groups: Group A--cyst growing,
      Group B--cyst not growing, and Group C--cyst absent. The prevalence of carpal
      tunnel syndrome was 100% (27/27) in Group A, 5.6% (1/18) in Group B, and 6.5%
      (6/93) in Group C. Growth of the cyst precedes the development of carpal tunnel
      syndrome by about 2 or 3 years. Growth of the bone cyst indicates that
      inflammation had already extended to the tenosynovium and median nerve. Cystic
      radio-lucency of the carpal bones appears to be a useful indicator of the onset
      of carpal tunnel syndrome.

PMID- 7822927
TI  - Cubital tunnel syndrome in a patient in long-term haemodialysis.
AB  - The onset mechanism of cubital tunnel syndrome and carpal tunnel syndrome may be
      similar in haemodialysis patients. Carpal tunnel syndrome is well recognized as a
      consequence of dialysis-associated amyloidosis. This case report documents the
      development of cubital tunnel syndrome in a patient on haemodialysis treatment
      for 10 years. Proliferating granulation tissue at the elbow had entrapped and
      displaced the ulnar nerve. This was corrected surgically, and the patient
      experienced immediate relief of the numbness and the "tingling", but the muscular
      atrophy had not improved after 8 months.

PMID- 7822928
TI  - Extensive subcutaneous calcification of the forearm in systemic lupus
      erythematosus.
AB  - We report two cases with long-standing systemic lupus erythematosus (SLE) who
      developed widespread calcification in subcutaneous tissue and peri-articular
      structures. To our knowledge only 26 case reports have appeared concerning this
      abnormality in SLE. However, there has been no report of calcification in an SLE
      patient in the literature of orthopaedic surgery. The calcifications of the
      forearm were marginally removed because of pain surrounding them. X-ray analysis
      revealed that the calcification was made of pure calcium phosphate.

PMID- 7822929
TI  - Soft tissue calcification in children with terminal transverse defects of the
      upper limb--is it tumoral calcinosis?
AB  - We report five children with transverse defects of the upper limb who developed
      calcified deposits at the distal end of the limb. The lesions were excised from
      two children and had the typical histological appearance of tumoral calcinosis
      but on clinical grounds it is unlikely that this is the same condition as that
      previously described as tumoral calcinosis.

PMID- 7822930
TI  - Tumoral calcinosis associated with congenital malformations of the hand.
AB  - Two cases of tumoral calcinosis are reported in children with congenital hand
      malformations. After excision of large calcific masses, reconstruction was
      performed using a free phalangeal graft in one case and a free toe transfer in
      the other.

PMID- 7822931
TI  - Abductor digiti minimi transfer for the restoration of opposition in children.
AB  - Abductor digiti minimi transfer was used to restore opposition in 20 patients,
      the majority suffering from congenital anomalies of the hand. The transfer was
      shown to be effective in restoring abduction, but less effective in restoring the
      rotational component of opposition in these cases. The donor site was critically
      reviewed and found to be acceptable. The surgical techniques and benefits of this
      transfer are reviewed.

PMID- 7822932
TI  - Myoelectric prostheses in the management of Poland's syndrome. A report of 2
      cases.
AB  - Two cases of Poland's syndrome are reported in whom myoelectric prostheses have
      been used. The rare congenital sporadic disorder of Poland's syndrome
      characterized by absence of pectoralis major and varying degrees of ipsilateral
      upper limb deficiency has been reported by various authors (Rasjad and Sutiaksa,
      1991, Gausewitz et al, 1984; David, 1982; Ireland et al, 1976). Management of the
      upper limb deficiency depends on the degree of functional and cosmetic
      disability. We report two cases of Poland's syndrome where myoelectric prostheses
      have been successfully used. We have been unable to find any published report of
      the use of a myoelectric prosthesis in Poland's syndrome.

PMID- 7822933
TI  - Extensor tendon sheath stenosis resulting in triggering of the little finger.
AB  - An isolated constriction of the tendon sheath of extensor digiti minimi caused
      triggering of the little finger. Incision of the tendon sheath resulted in
      recovery of frictionless gliding of the tendon.

PMID- 7822934
TI  - Predictors of neurovascular displacement in hands with Dupuytren's contracture.
AB  - A prospective study of hands with Dupuytren's contracture was designed to test
      the association of three variables, the presence of an interdigital soft tissue
      mass, the presence of flexion contractures at each digital joint, and the
      duration of contracture, with the formation of spiral nerves. 66 digits in 37
      hands affected by Dupuytren's disease were examined intra-operatively. Of the 34
      digits (52%) with spiral nerves, 28 had soft tissue masses (42%). The sensitivity
      of a soft tissue mass alone as a predictor of a spiral nerve was 59% and the
      specificity 75%. The presence of a flexion contracture at the PIP joint had a
      sensitivity of 88% and a specificity of 62% for the presence of a spiral nerve.
      The combination of a soft tissue mass and a PIP joint contracture was a very
      specific (94%) but not a particularly sensitive (50%) test for spiral nerve
      formation. The formation of a spiral nerve is progressive, occurring most often
      in hands with significant PIP joint contractures with or without soft tissue
      interdigital masses.

PMID- 7822935
TI  - A medieval casebook: hand cures documented in the Icelandic Sagas of bishops.
AB  - The Sagas of Icelandic bishops composed in and around the 13th century reveal
      something of the incidence and treatment of various hand conditions in the
      medieval period. A selection from the relevant material is translated and
      discussed.

PMID- 7822936
TI  - Upper arm and forearm tourniquet tolerance.

PMID- 7822937
TI  - Location, location, and location: real estate and inflammation.

PMID- 7822938
TI  - Expression of CD21 and synthesis of its ligands by HeLa cells after growth in
      serum-free medium.
AB  - We examined the synthesis of C3 and the expression of CD21 (complement receptor
      type 2) by epithelial cells in serum-free culture to eliminate the effects of
      competing C3 fragments from serum supplementation. The mean C3 content of HeLa
      supernatants was twice that of lysates after 4 hours in culture.
      Immunoprecipitation of metabolically labeled proteins from supernatants and
      lysates detected the structures of pro-C3 and native C3 in both supernatants and
      lysates, with C3 fragments iC3b and C3dg detected in supernatants only.
      Hybridization of total RNA with a human C3 complementary DNA probe revealed bands
      consistent with the full-length C3 message at 5 to 6 kb, implying that the C3
      fragments found in the supernatants were the result of posttranslational
      processing. Hybridization of HeLa messenger RNA with complementary DNA probes for
      human complement receptors revealed strong expression of CD21 message but failed
      to detect message for CD35 (complement receptor type 1) or CD18 (beta chain of
      complement receptor types 3 and 4). Immunofluorescence with the monoclonal
      antibodies OKB7 and HB-5 confirmed abundant surface expression of CD21 under
      serum-free conditions. In a [3H]thymidine uptake assay polyclonal anti-C3
      inhibited HeLa proliferation for 4 hours compared with an identical concentration
      of polyclonal anti-C5 as control. Thus, in contrast to previous reports, we have
      observed abundant CD21 message at approximately 5 kb and strong surface
      fluorescence with anti-CD21 monoclonal antibodies in HeLa cells cultured under
      serum-free conditions. Serum-free conditions may help to promote the interaction
      of constitutively produced C3 or C3 fragments with CD21 on malignant epithelium.

PMID- 7822939
TI  - Sustained vasoconstriction associated with daily cyclosporine dose in heart and
      lung transplant recipients: potential pathophysiologic role of endothelin.
AB  - Transient decreases in glomerular filtration rate (GFR) and renal plasma flow
      (RPF) have been associated with each daily dose of cyclosporine (CYA) in patients
      with renal allografts. We examined the differential dose effects of CYA on native
      renal function in 24 recipients of heart or lung transplants (treated with 7.3 +/
      0.5 mg/kg/day [mean +/- SEM]) and in seven patients with psoriasis (treated with
      4.2 +/- 0.7 mg/kg/day). GFR and RPF were measured by urinary inulin and para
      aminohippuric acid clearances 2 hours before the morning CYA dose and for 6 hours
      after. The age of heart and lung transplant recipients at renal study (2 months
      after transplantation) was 47 +/- 2.0 years. Their serum creatinine levels rose
      from 80 +/- 4.0 mumol/L during the first week after transplantation to 120 +/-
      4.0 mumol/L at renal study (p < 0.0001). Their GFR and RPF were decreased before
      the CYA dose at 64 +/- 2.4 and 340 +/- 16 ml/min per 1.73 m2 and did not vary
      during the study. In comparison, the age of patients with psoriasis was 51 +/-
      4.6 years at renal study (24 +/- 4.0 months after CYA treatment). Their serum
      creatinine levels rose from 80 +/- 4.0 mumol/L before treatment to 100 +/- 10
      mumol/L at renal study (p = 0.07). Transient decreases of their baseline GFR and
      RPF (85 +/- 7.4 and 380 ml/min per 1.73 m2) with a nadir occurring during the
      first 2 hours of CYA ingestion were observed together with the recovery of these
      parameters toward baseline by the end of the study.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7822940
TI  - Cardiac baroreflex sensitivity and sodium excretion are reduced both by a deficit
      and an excess of dietary salt in the conscious dog.
AB  - In 10 conscious, chronically instrumented beagle dogs we studied the effects of
      four different dietary sodium intakes (mmol Na/kg body wt/day: 14.5 [excess], 7.5
      [high], 2.5 [normal], and 0.5 [low] [plus an additional standardized sodium
      depletion produced by peritoneal dialysis several days before the experiments])
      on cardiac baroreflex sensitivity and renal response to an acute saline load.
      Full sigmoid barocurves were produced by intravenous injection of phenylephrine
      (2.5 to 20 micrograms/kg) and nitroglycerine (2.5 to 30 micrograms/kg). The gain
      of this relationship was significantly decreased by both an excess and low sodium
      intake (8.0 +/- 1.0 and 8.3 +/- 0.8 beats/min/mm Hg, respectively) when compared
      with the 2.5 and 7.5 (12.1 +/- 1.4 and 16.0 +/- 1.7 beats/min/mm Hg,
      respectively) mmol Na/kg/day sodium intake. Water and sodium excretion in
      response to saline infusion were lower in the 0.5 and 14.5 mmol/kg/day sodium
      intake groups in spite of the higher atrial natriuretic peptide and lower plasma
      renin activity and plasma aldosterone levels in the latter. Mean arterial blood
      pressure, heart rate, and central venous pressure increased during saline loading
      in all groups; hematocrit and plasma protein concentration decreased similarly in
      all groups. The results suggest that the rapid renal homeostatic response to an
      acute salt load in animals kept chronically on normal or moderately increased
      dietary sodium intake is regulated by baroreflex control of the renal homeostatic
      response. Excess dietary sodium intake attenuates baroreflex sensitivity and
      delays sodium and water excretion after acute loading.

PMID- 7822941
TI  - Diabetes mellitus: can abnormally controlled wound healing lead to
      glomerulosclerosis?

PMID- 7822942
TI  - Toward an understanding of the pathophysiologic mechanism of thrombosis in the
      antiphospholipid antibody syndrome.

PMID- 7822943
TI  - Rationale for juxtacrine regulation of neutrophil interactions with the
      stimulated endothelium.

PMID- 7822944
TI  - Oxidants and signal transduction in vascular endothelium.

PMID- 7822945
TI  - In vivo effects of hyperglycemia on the outcome of acute mesangial injury in
      rats.
AB  - To assess the effects of high blood glucose concentration on glomerular changes
      after the acute mesangial cell injury in the rat, the monoclonal anti-Thy1.1
      antibody OX-7 was injected into streptozoticin-induced diabetic rats or normal
      rats. The increase in proliferating cell nuclear antigen-positive cells in
      glomeruli at day 4 and glomerular hypercellularity at day 18 was less prominent
      in diabetic rats than in normal rats. The expansion of mesangial matrix area
      assessed by fibronectin immunostaining was more prominent, and segmental
      glomerulosclerosis was observed at day 60 in the diabetic rats. These data
      suggest that the insulin-deficient group may reflect impaired "wound-healing,"
      leading to the prolonged ECM accumulation under the hyperglycemic condition in
      vivo.

PMID- 7822946
TI  - Acquired protein C dysfunction but not decreased activity of thrombomodulin is a
      possible marker of thrombophilia in patients with lupus anticoagulant.
AB  - Lupus anticoagulants (LAs) are acquired antiphospholipid antibodies, and the
      occurrence of LA is associated with an increased risk of developing thrombosis.
      In a population of 46 patients with LA with or without LA-associated
      thrombophilia, it was analyzed whether the concentration of LA could be
      correlated to the individual thrombotic risk in patients with LA. No significant
      difference was found in the concentrations of LA measured by routinely used
      functional and immunologic assays in patients with LA with thrombophilia when
      compared with patients with LA without thrombophilia. Inhibition of
      thrombomodulin (TM) activity by LA has been postulated to be one of the major
      pathogenic mechanisms causing thrombophilia in LA. Therefore the inhibition of
      endothelial cell-dependent TM activity by LA was analyzed by using a protein C
      (PC) activation assay. Reduced rates of PC activation were found in only 2 out of
      the 46 cases, ruling out that inhibition of TM activity is a common phenomenon in
      patients with LA. However, anionic phospholipids are necessary to ascertain the
      anticoagulant activity of activated PC (APC). To prove the hypothesis that the
      anticoagulant activity of APC is inhibited by LA, the anticoagulant response of
      purified APC added to LA-containing plasma was measured through the amount of
      factor VIII inactivation. Thirteen out of 14 patients with recurrent thrombotic
      events and 10 out of 19 patients with one single episode of thrombosis showed an
      APC response outside the mean--2 SD range of normal human controls. In contrast,
      among 13 patients with LA without symptoms, only one showed an abnormal APC
      response. From these data it is concluded that LA inhibits the APC anticoagulant
      activity and that this type of acquired APC dysfunction may contribute to the
      pathogenesis of LA-associated thrombophilia. Moreover, the APC anticoagulant
      response assay may prove to be a useful marker to identify patients with LA with
      a high thrombotic risk.

PMID- 7822947
TI  - Effects of immature recruitable collaterals on myocardial blood flow and infarct
      size after acute coronary occlusion.
AB  - This study assessed the ability of immature recruitable coronary collateral
      vessels to alter regional myocardial blood flow and to protect jeopardized
      myocardium from infarction after acute coronary occlusion. An inflatable balloon
      occluder was placed around the left circumflex coronary artery of 7 dogs (group
      A), while nine dogs (group B) underwent placement of an Ameroid constrictor
      around the circumflex artery proximal to a balloon occluder. Group A dogs were
      studied 2 to 3 days after surgery; those in group B were studied 12 days after
      surgery, when partial collateralization had occurred. The circumflex artery was
      acutely occluded in both groups for 4 hours. Myocardial blood flow was measured
      with radioactive microspheres before, immediately after, and 4 hours after
      coronary occlusion. Infarct size, expressed as percent of left ventricular area
      at risk, was determined by triphenyl tetrazolium chloride staining after infusion
      of colored dyes to delineate perfusion beds. Flows in the ischemic circumflex bed
      90 seconds after coronary occlusion decreased in both groups for both endocardial
      (0.04 +/- 0.02 ml/min/gm vs 0.09 +/- 0.04 ml/min/gm) and epicardial (0.19 +/-
      0.07 ml/min/gm vs 0.26 +/- 0.08 ml/min/gm) layers. Four hours after coronary
      occlusion, endocardial flow did not rise significantly in group A (0.11 +/- 0.05
      ml/min/gm), but increased significantly in group B to 0.52 +/- 0.13 ml/min/gm (p
      < 0.05). Epicardial flow at 4 hours was also significantly greater in group B
      (1.03 +/- 0.15 ml/min/gm) than in group A (0.55 +/- 0.13 ml/min/gm, p <
      0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7822948
TI  - Activation of monocytes via their Fc alpha R increases procoagulant activity.
AB  - There is increasing evidence in experimental models of glomerulonephritis,
      including IgA nephropathy, that macrophages accumulate within the affected
      kidneys. Increased procoagulant activity (PCA) consequent on the influx of these
      cells has been associated with the progression of kidney disease. We have studied
      the effect of activation of the monocyte Fc alpha receptor (Fc alpha R) on PCA.
      Immune complexes of immunoglobulin A (IgA) isotype formed in situ or the addition
      of aggregated IgA resulted in a dose-dependent increase of monocyte PCA. Maximal
      effect was achieved after 6 hours of incubation. PCA induced by Fc alpha R was
      consistent but was less than that observed after addition of endotoxin to
      monocyte monolayers or after activation via the Fc gamma R or mannose receptor.
      Specificity of the interaction of the ligands with Fc alpha R was shown;
      galactose inhibited effects mediated via the Fc alpha R but not via the Fc gamma
      R. Corticosteroids inhibited Fc alpha R monocyte-induced PCA. These results are
      likely to be relevant in the immunopathogenesis of IgA-mediated disease,
      particularly IgA nephropathy.

PMID- 7822949
TI  - Idiotypic and anti-idiotypic antibodies interfere in a standard radioimmunoassay
      for beta-endorphin.
AB  - Human anti-beta-endorphin and anti-idiotypic antibodies competitively inhibited
      the binding of rabbit anti-beta-endorphin antibodies to beta-endorphin.
      Furthermore, human and rabbit antibodies demonstrated cross-reactive idiotypic
      binding interactions. Competition for binding to beta-endorphin and idiotypic
      binding between human and commercially produced rabbit antibodies interfered in a
      standard radioimmunoassay to detect beta-endorphin. Purified human anti-beta
      endorphin antibodies falsely elevated the calculated concentrations of samples
      with standardized concentrations of beta-endorphin. Anti-beta-endorphin
      antibodies were also falsely measured as beta-endorphin in samples that did not
      contain beta-endorphin. In contrast, anti-idiotypic antibodies lowered the
      calculated concentrations. These data suggest the occurrence of complex
      competition between several competitors rather than inhibition by a single
      competitor (i.e., unlabeled peptide) in subjects that produce specific antibody.
      Competitive and idiotypic binding interactions between human and animal
      antibodies may affect radioimmunoassay for other substances in subjects that
      produce specific antibodies.

PMID- 7822951
TI  - Managed care conference.

PMID- 7822950
TI  - Low-density lipoprotein stimulation of mesangial cell fibronectin synthesis: role
      of protein kinase C and transforming growth factor-beta.
AB  - Low-density lipoprotein (LDL) cholesterol has been implicated in the pathogenesis
      of glomerulosclerosis in diabetes and other forms of glomerular injury. In the
      present study we evaluated the effect of LDL on fibronectin synthesis in cultured
      rat mesangial cells (MCs) and the roles of protein kinase C (PKC) and
      transforming growth factor-beta (TGF-beta) in mediating this LDL action. In MCs,
      25 micrograms to 100 micrograms/ml LDL increased PKC activity within 15 minutes,
      as reflected by enhanced in situ phosphorylation of the 80 kd myristoylated
      alanine-rich C kinase substrate protein, a specific endogenous substrate of PKC
      in MC. The same concentrations of LDL subsequently (18 to 72 hours) enhanced
      fibronectin synthesis, as reflected by increased incorporation of labeled
      methionine into fibronectin. GF 109203X, a selective inhibitor of PKC, blocked
      increases in both PKC activity and fibronectin synthesis induced by LDL in MCs.
      Furthermore, prior downregulation of PKC to less than 1% of basal activity by
      exposure of MCs to 0.5 mumol/L phorbol myristate acetate (PMA) also prevented LDL
      stimulation of fibronectin synthesis. The activation of PKC by LDL seen after 15
      minutes of exposure was transient and was not observed after 4 or 48 hours of
      exposure of MCs to LDL. However, exposure to LDL for 48 hours, but not for 15
      minutes or 4 hours, increased both maximal PKC responses to phorbol dibutyrate
      (PDBu) and tritiated PDBu binding to MCs by 30%. These findings suggest that
      chronic exposure to LDL increases the total PKC content in MCs and thereby might
      modulate responses to other PKC agonists. Neither the cyclooxygenase inhibitor
      piroxicam nor the thromboxane/prostaglandin endoperoxide receptor blocker Sq
      29548 altered LDL stimulation of fibronectin synthesis in MCs, suggesting that
      this action of LDL was not mediated by changes in MC eicosanoid generation. By
      contrast, antibody to TGF-beta blocked LDL stimulation of fibronectin synthesis
      in MCs. TGF-beta bioactivity, determined with the mink lung epithelial cell
      assay, was two to three times higher in the medium of MCs cultured with LDL for
      24 to 48 hours as compared with corresponding control values. Total TGF-beta
      bioactivity examined after heat activation of latent TGF-beta was also two times
      higher in the medium of MCs exposed to LDL as compared with that of controls.
      Prior down-regulation of PKC by exposure of MCs to PMA blocked the increases in
      TGF-beta bioactivity induced by LDL.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7822952
TI  - Vandals at the gates of medicine (Part II)

PMID- 7822953
TI  - Raging rivers: doctors to the rescue.

PMID- 7822954
TI  - Philanthropy and the free society.

PMID- 7822955
TI  - The Balkans--delivering hope amidst tragedy.

PMID- 7822956
TI  - Philanthropy and citizenship.

PMID- 7822957
TI  - Making a difference in Haiti. Can-do doctors confront the agonies of health care
      desparation in Haiti.

PMID- 7822958
TI  - Hypertension, a controllable risk factor--does it really matter?

PMID- 7822959
TI  - Forestalling malpractice. Providing quality health care in a war zone.

PMID- 7822960
TI  - Antitrust reform from the physicians' perspective.

PMID- 7822961
TI  - White House releases task force documents.

PMID- 7822962
TI  - Is it pseudo or is it science?

PMID- 7822963
TI  - Health care reform: an historic perspective.

PMID- 7822964
TI  - Managed competition: a day with Paul Ellwood, MD.

PMID- 7822965
TI  - Re: Guns in the medical literature (March and May)

PMID- 7822966
TI  - Re: Guns in the medical literature (March and May)

PMID- 7822967
TI  - Re: Guns in the medical literature (March and May)

PMID- 7822968
TI  - Re: Guns in the medical literature (March and May)

PMID- 7822969
TI  - Health Reform Consensus Act of 1994.

PMID- 7822970
TI  - Doctors fight government intervention with judicial activism.

PMID- 7822971
TI  - Avoiding managed care's liability risks.

PMID- 7822972
TI  - Physician, bail thyself out!

PMID- 7822973
TI  - Litigation's impact on society.

PMID- 7822974
TI  - The role of nondepolarizing neuromuscular blocking agents in mechanically
      ventilated patients.
AB  - Prolonged use of the nondepolarizing neuromuscular blocking agents in the
      critical care setting has greatly increased in the recent past. Accompanying the
      increased use of these agents are numerous accounts of long-lasting adverse
      outcomes such as muscular atrophy and neuropathy that can be attributed to
      pharmacologic paralysis. There has been a financial impact on hospitals as well.
      Responding to these facts, the medical staff at the Medical College of Georgia
      Hospital and Clinics recently approved guidelines for the use of nondepolarizing
      neuromuscular blocking agents in the intensive care setting. These guidelines
      recommend clinical indications for these agents and dosing ranges reflecting
      current medical opinion.

PMID- 7822975
TI  - The malpractice reform conundrum: does reducing frivolous claims simply lead to
      more pre-trial appeals?

PMID- 7822976
TI  - Health system reform.

PMID- 7822977
TI  - HTLV-I antibody screening in donated blood and thalassemic patients.
AB  - The HTLV-I antibody screening by passive partial agglutination test, Serodia HTLV
      I (Fuji-rebio Inc) was performed in a total of 1,225 male and 468 female blood
      donors from September 1992 to March 1993. In addition, a total of 64
      multitransfused thalassemic patients were also studied. All of the sera from
      donors and patients in both study groups showed no reactive results for HTLV-I
      antibody. This finding indicated that the HTLV-I infection is not yet a problem
      in blood transfusion in Thailand. However, the scattered reports of HTLV-I
      infections from our region should urge the national authority on the surveillance
      of this infection by epidemiological survey and occasional screening in blood
      donors.

PMID- 7822978
TI  - Transmission of HIV infection by seronegative blood in Thailand.
AB  - In Thailand, the prevalence of HIV infection in the general population and in
      donor blood (DB) has sharply increased since 1987. The HIV seropositive rate in
      DB was increased from 0.0065 per cent in 1987 to 0.95 per cent in 1993 (150 times
      in 6 years). Heterosexual transmission is the major route of spreading.
      Therefore, HIV seronegative blood (SNB) poses significant hazard to the
      recipients because of the risk of viraemia during the window period of early HIV
      infection. In Thailand HIV Ab screening in all units of blood was started in 1987
      and was compulsory nationwide in early 1989. Donor self exclusion (DSE) has been
      implemented since 1990. It is not fully effective in the prevention of
      transfusion associated AIDS (TAA) because of many limiting factors. However, DSE
      should be promoted to practice in every blood bank particularly those that can
      not do HIV Ag screening. During 1990-1992, there were 30 reported cases of TAA by
      SNB. The study of risk figure (HIV Ag positive-neutralization with HIV Ab
      negative) in DB was 1:3,400 and 1:10,000 in two reports in 1991. Under all these
      circumstances, the national AIDS committee has documented the policy to do HIV Ag
      screening in every unit of blood from August 1991 and allocated a 10 million baht
      budget (year 1992) for Ag testing. Several hospitals and NBC reported the risk
      figures which varied from 1:3,400 to 1:25,000. A certain amount of blood is
      processed to 2-4 blood components given to 2-4 patients which will increase the
      number of TAA by SNB.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7822979
TI  - Neonatal intensive care: present and future trends in Thailand.

PMID- 7822980
TI  - Early neonatal mortality and causes of death in Ramathibodi Hospital: 1981-1990.

PMID- 7822981
TI  - Neonatal septicemia and immunotherapy.

PMID- 7822982
TI  - Effects of multivitamin supplementation for improvement of thiamin, riboflavin,
      and retinol nutrition in pediatric patients.
AB  - The effect of multivitamin supplementation on thiamin, riboflavin and retinol
      nutrition was studied in ten male chronic pediatric patients at Ramathibodi
      Hospital. MTV forte (Government Pharmaceutical Organization) was given 1 tablet
      daily for ten days and the effect was compared with the preceding ten-day control
      period. Anthropometric biochemical, clinical and dietary assessments were
      performed throughout the study. Biochemical assessments of vitamin nutrition at
      the beginning and the end of a 10-day non-supplementation period revealed
      multiple vitamin deficiencies in the subjects, though clinical manifestation was
      not seen. Hospital diets improved vitamin nutrition of some patients but most of
      them still showed subclinical vitamin deficiencies. Improvement of vitamin
      nutrition was clearly shown in most patients after MTV supplementation. Multiple
      vitamin supplements should be prescribed in high-risk patients since there was no
      definite pattern of vitamin deficiencies in various diseases and early detection
      of vitamin deficiency was difficult to perform. The dosage between 1-2 times of
      RDA was considered adequate in most of our patients.

PMID- 7822983
TI  - Acute myelopathy in children.

PMID- 7822984
TI  - Vitamin E status, glutathione peroxidase activity and the effect of vitamin E
      supplementation in children with thalassemia.
AB  - Vitamin E and selenium statuses were studied in thalassemic children in
      comparison with 16 normal controls. Twelve Hb H disease, 46 beta-thal/Hb E and 7
      beta-thal major patients had lower plasma vitamin E level than controls but
      plasma vitamin E/total lipids ratio of Hb H disease subjects was not different
      from normal. Twelve Hb H disease and 33 beta-thal/Hb E patients had normal RBC Se
      but increased RBC GSH-Px activity. Ten vitamin E-deficient thalassemic subjects
      had been supplemented with 200 mg of oral vitamin E for 4-8 weeks. After
      supplementation, their plasma vitamin E increased and H2O2 hemolysis decreased to
      normal values. Their RBC GSH-Px activity also decreased but hematocrit did not
      change significantly. The results demonstrate that some types of thalassemic
      patients have vitamin E deficiency and support that vitamin E and selenium have
      related functions in the prevention of RBC oxidation. Vitamin E supplementation
      increased RBC resistance to oxidative damage.

PMID- 7822985
TI  - Stable asthma. How stable is it?

PMID- 7822986
TI  - Etiology, treatment and outcome of hospitalized pneumonia in young children at
      Ramathibodi Hospital.

PMID- 7822987
TI  - Apnea documentation for determination of brain death in Thai children.

PMID- 7822988
TI  - Nasopharyngeal continuous positive airway pressure in postextubation stridor
      infants.

PMID- 7822989
TI  - Evaluation of a computerized spirometer used in children.

PMID- 7822990
TI  - Correlation of roentgenologic diagnosis and etiologic agents of pneumonia in thai
      children under 5 years of age.
AB  - An attempt to distinguish between viral and bacterial pneumonia from radiographs
      is usually difficult unless there is a pathognomonic type of infiltration such as
      parahilar peribronchial infiltration commonly seen in viral pneumonia which can
      be usually be differentiated easily from that of bacterial pneumonia. Percentage
      of agreement of roentgenographic diagnosis for bacterial pneumonia, viral
      pneumonia and mixed infection is about 53, 73.3 and 63.9 per cent respectively.

PMID- 7822991
TI  - Primary vesicoureteric reflux in Thai children with urinary tract infection.
AB  - Four hundred and forty-three pediatric patients were analysed retrospectively for
      GU anomalies especially for primary VUR. Genito urinary tract anomalies were
      found in 46 per cent of investigated patients. Primary VUR was found in 29 per
      cent of patients who had GU anomalies and were the most common anomalies found.
      The GU anomalies were found more in younger males, and older females. Low to
      medium grade VUR tended to have spontaneous resolution and correlated well with
      degrees of controlling infection. In high grade VUR, fewer patients may have
      spontaneous resolution, surgery can correct the reflux but not the progression of
      the damage.

PMID- 7822992
TI  - Spinal cord tumors in children: a clinical study at Ramathibodi Hospital.

PMID- 7822993
TI  - Laboratory investigation utilization in pediatric out-patient department
      Ramathibodi Hospital.
AB  - HYPOTHESES: Laboratory investigations are inappropriately utilized in the
      Pediatric OPD of Ramathibodi Hospital and this is due to lack of knowledge and
      unawareness of the cost of tests. OBJECTIVES: 1) To obtain information on
      laboratory utilization. 2) To evaluate the appropriateness of the residents' test
      ordering behavior. 3) To estimate the cost of unnecessary tests. 4) To reduce the
      utilization by combined education, feedback, and peer-review strategies. STUDY
      DESIGN: Randomized controlled trial carried out from January 1987 to May 1988,
      consisting of pre-intervention period (Jan-May 1987). intervention period (June
      November 1987), and post-intervention period (July 1987-May 1988). STUDY
      POPULATION: There were 3 intervention groups and 3 control control groups which
      were stratified by level of seniority as 10 first year residents (R1I vs R1C), 8
      second year residents (R2I vs R2C), and 18 staff (SI vs SC). INTERVENTION: For
      the residents, education on diagnostic tests, chart audit and feedback on their
      test ordering behavior were provided twice a week. The second year residents also
      played an active role in giving comments on the first year residents'
      performances. For the staff, the strategy used was peer-review. The simulated
      cases derived from the actual medical records serviced by the residents were
      reviewed and rated, according to the appropriateness of the residents' test
      ordering behavior, from 0 (poor) to 10 (excellent). A score of less than 5 was
      considered to indicate inappropriate ordering behavior. OUTCOME: 1) Numbers and
      cost of tests per patient for each group. 2) The achievement of a score
      indicating appropriate test ordering behavior of the resident groups. STATISTICAL
      ANALYSIS: Kruskal-Wallis test, Mann Whitney test, Wilcoxon test and Chi-square
      test. RESULTS: 1. The utilization pattern was not correlated to the level of
      seniority of the physicians. 2. There was inappropriate laboratory utilization in
      this group of residents: overutilization defined as should not be ordered
      (26.9%), and underutilization defined as should have been ordered (17.7%). Most
      of the inappropriateness occurred in the ordering of microbiology (50%) and
      special blood chemistry (40%). 3. Only the number of tests per patient ordered by
      the R2I group was significantly lower than that of the R2C group in the late post
      intervention period. The cost of tests per patient ordered by the R2C group was
      significantly increased as compared to their baseline. This suggested that the
      combination of education, chart audit and active feedback strategies was more
      effective than each strategy alone. 4. The appropriateness of the test ordering
      behavior of the resident intervention groups improved during the post
      intervention period, although the change was not statistically significant. The
      control groups' behavior was statistically worse. This suggested that the
      strategy prevented the inappropriateness of test ordering behavior. 5. With the
      intervention, the overutilization significantly decreased while the
      underutilization increased. The underutilization might be a consequence of cost
      containment on laboratory utilization. 6. The cost of unnecessary tests accounted
      for 17.6 per cent of the total cost of tests ordered by the residents.

PMID- 7822994
TI  - Screening for congenital hypothyroidism in Thailand: has its time come?
AB  - The incidence of congenital hypothyroidism at Ramathibodi Hospital was
      approximately 1:2,486-1:3,843 livebirths, comparable to those found in other
      industrialized countries. The screening program utilizing TSH measured by a kit
      manufactured in Thailand was accurate and cost-benefit. It is time to organize
      TSH screening at least in a university hospital in Thailand to prevent the social
      burden of raising mentally-handicapped children.

PMID- 7822995
TI  - Childhood trauma, country report (Thailand).
AB  - In Thailand, each year approximately 15,000 people die from accidents, a figure
      exceeded only by cardiovascular diseases. Motor vehicle accidents (MVA) is the
      principal cause of death and injuries in children of all ages except preschool
      group. In 1988 there were 554,452 cases of injuries out of which 10,031 died from
      MVA. In Bangkok alone MVA accounts for an average of 300 childhood and teenage
      death and 1,900 cases of injuries each year. Falls, burns and poisonings are
      relatively high in children less than 4 years old while MVA and injuries from
      sharp and blunt objects of both accidental and non-accidental cases increase with
      age and become the two leading causes of injury in older children. The sex ratio
      (F:M) in preschool ages are 1:1.4 and 1:2 in preteen. Poisonings, though less
      common, are considered to be very important because of their severity. Drugs,
      hydrocarbon, insecticides, lead and corrosive substances are leading agents. As
      for injuries caused by animals, 150 cases of rabies were reported each year while
      around 5,000 cases of snake bites were found in 1987 and 20 per cent of the
      victims were children. The study from Ramathibodi Hospital revealed that the
      majority of accidents (65-72%) occur at home and 20 per cent in the street in
      children younger than 12 years. Peak incidence were found between 5-9 pm. During
      weekend and holidays the incidence is higher. Ninety-five per cent of the
      accidents reported were mild cases, 15 per cent moderate, 3 per cent severe and
      less than 1 per cent caused death.

PMID- 7822996
TI  - Double aneuploidy: 46,X, +21 a combination of Down syndrome and Turner syndrome.

PMID- 7822997
TI  - Neonatal lupus erythematosus in Thailand.
AB  - Systemic lupus erythematosus (SLE) is not uncommon in Thai children and adults
      but neonatal lupus erythematosus has never been reported in Thailand. A case of
      NLE born of a mother without prior history of SLE was reported. He was initially
      misdiagnosed as congenital self-healing histiocytosis because of seborrheic
      dermatitis-like lesions, petechiae, hepatosplenomegaly and thrombocytopenia.
      Features supporting the diagnosis of NLE in this case were presented.

PMID- 7822998
TI  - Disseminated Burkitt's lymphoma in a child with AIDS.
AB  - Rarity of HIV-associated disseminated lymphomas in children initiated this
      report. The patient was an 18-month-old girl who had a history of chronic
      cervical lymphadenopathy since 6 months of age. She was first seen because of
      rapid enlargement of an inguinal lymphnode. The bone marrow aspirate was
      compatible with Burkitt's lymphoma, L3 cell-type. She was treated with
      chemotherapy without satisfactory success. She developed neurological involvement
      of lymphoma. Accidental sharp injury which contaminated her blood, in a medical
      personnel leaded to having her blood tested for anti-HIV and it was found
      positive. Her mother had positive anti-HIV presumably acquired from blood
      transfusion after an abortion in early 1988. It occurred before the donated blood
      was compulsively tested for anti-HIV. She died at the age of 24 months.

PMID- 7823000
TI  - Intestinal myiasia: a case report.

PMID- 7822999
TI  - Aeromonas hydrophila epiglottitis: a case report.

PMID- 7823001
TI  - Congenital complete absence of GH, TSH and PRL in infants: a consequence of Pit-1
      gene deletion.
AB  - The patient was the first child of a short mother (140 cm) born at term with a
      birthweight of 2,700 g. On arrival, she was 1 4/12-year-old, weighed 4,150 g and
      47 cm long. Her bone age was at the 6 month-old level. Endocrine investigation
      revealed undetectable plasma growth hormone (GH), thyrotropin (TSH) and prolactin
      (PRL) levels. CT scan of ovaries revealed bilateral ovarian agenesis in spite of
      normal, 46 XX karyotype. MRI of the brain did not demonstrate intracranial tumor
      or congenital malformation. Peak plasma GH level after oral clonidine
      provocation, insulin induced hypoglycemia, and I.V. GH-RF stimulation were 0.6,
      0, and 0 ng/ml respectively. Peak plasma TSH response after I.V. TRH stimulation
      was 0.04 microU/ml. The patient could not secrete PRL at any time after insulin
      induced hypoglycemia, TRH and metoclopramide stimulations. On the other hand the
      child had elevated basal plasma cortisol (38 micrograms/dl at 8.00 AM) and raised
      24 hr urinary 17 OHCS excretion (50 mg/1 g Cr against normal value of 3 mg/1 g
      Cr) without evidence of Cushing syndrome probably indicate partial glucocorticoid
      resistance. Peak plasma cortisol responses after intravenous metoclopramide and
      insulin induced hypoglycemia were 46 and 42.9 micrograms/dl respectively.
      Dexamethasone administration reduced plasma cortisol to 2.9 micrograms/dl. The
      child had also elevated basal plasma FSH (36 microU/ml) and LH (5 microU/ml) with
      further elevation to the peak of 123 and 99 microU/ml respectively after LHRH
      stimulation. All evidence suggested the diagnosis of congenital complete absence
      of GH, TSH, and PRL which is characteristic of Pit-1-gene deletion.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7823002
TI  - Hepatopathy-thrombocytopenia vs infection-induced hemophagocytic syndrome in
      Wilms' tumor: a case report.
AB  - A 3-year-old boy with Wilms' tumor, post operative left nephrectomy stage, had
      HTS on day 99 of the combined chemotherapy which lasted for more than 20 days. He
      had severe respiratory distress due to a moderate amount of ascites and marked
      pleural effusion. Because of high fever, thrombocytopenia and marked
      hemphagocytosis in the bone marrow, he received IVIG for 2 days. Normal platelet
      count and markedly decreased pleural fluid were attained within 3 days. He
      subsequently tolerated full doses of combined chemotherapeutic agents with an
      additional one (doxorubicin). In cases of HTS, IAHS should be suspected. The bone
      marrow should be done and treatment accordingly so that there is no need to
      decrease, the dosage of chemotherapeutic agents afterwards.

PMID- 7823003
TI  - Multiple sclerosis in children: a report of 17 Thai pediatric patients.

PMID- 7823004
TI  - Prolactin (PRL) release in normal and growth hormone deficient children after
      oral metoclopramide.
AB  - Studies were done to determine plasma PRL in response to oral MC 0.2 mg/kg in 17
      normal children (NC), 12 males and 5 females aged between 4.7-12.8 years and in
      26 idiopathic growth hormone deficient children (IGHD), 15 M, 11 F, between 1.5
      14.7 years old. Peak serum GH levels above 10 ng/ml after clonidine test and
      during insulin induced hypoglycemia were used to distinguish these 2 groups. None
      of the subjects had secondary sex characteristics. Adrenocortical and thyroid
      disorders were excluded. The subjects were fasted overnight. Blood samples for
      PRL determination were obtained at 0, 60, 90, 120 min after oral MC. In 17 NC the
      basal serum PRL values ranged from 0 to 19.2 ng/ml with the mean +/- SE of 7.24
      +/- 1.7 ng/ml. The peak serum PRL response to MC ranges were from 33 to 127 ng/ml
      with the mean +/- SD and +/- SE of 64.45 +/- 24.22 and +/- 5.88 ng/ml
      respectively giving the cut point-2SD value of 16.01 ng/ml. Among 26I GHD, only 2
      patients (7.69%) being all male, had peak PRL response to MC below 16.01 ng/ml,
      whereas, the rest (92.31%) had peak PRL levels above it. It is concluded that
      oral MC 0.2 mg/kg is the potent PRL stimulator in children, which can be safely
      used to test pituitary PRL secretion effectively. The majority (92.31%) of
      idiopathic GH deficient children had adequate serum PRL response to oral MC,
      whilst 7.69 per cent disclosed inadequate response which might indicate different
      etiologies.

PMID- 7823005
TI  - Comparison of efficacy of peptilose-base ORS (ORALNU) and WHO-ORS.
AB  - We examined whether replacing glucose with Peptilose into standard ORS would be
      advantageous over WHO-ORS. A study was carried out on 134 diarrheal children with
      mild to moderate dehydration. They received either WHO-ORS or Peptilose-ORS by
      randomized selection. In only two cases in each group, diarrhea was caused by
      Vibrio cholerae non 0-1. Significant per cent weight gain was observed in
      patients with Peptilose-ORS compared to those treated with WHO-ORS (P = 0.046).
      The patients could voluntarily take a higher amount of Peptilose-ORS and had
      significantly less stool output in the combined mildly and moderately dehydrated
      patients. It is concluded that Peptilose-ORS is more advantageous and acceptable
      than the standard WHO glucose-ORS for treatment of non cholera and 2 cases of
      cholera dehydrating diarrhea in children.

PMID- 7823006
TI  - Gastroesophageal reflux in children: correlation of symptoms with 24-hour
      esophageal pH monitoring.
AB  - To evaluate the clinical significance of suspected symptoms of GER, 24-hour
      esophageal pH monitoring was performedin 55 children (mean age of 23.9 months).
      We used 24-hour esophageal pH monitoring as a gold standard for the diagnosis of
      pathological GER. The primary indication for the study included frequent
      vomiting, dysphagia and respiratory diseases (recurrent pneumonia, aspiration
      pneumonia, hyperreactive airway, apnea and stridor). Forty-seven per cent of
      these 55 children had pathological GER and 61.5 per cent of them were less than 1
      year-old. The sensitivity of frequent vomiting, dysphagia and aspiration
      pneumonia as symptoms of GER was lowest (7.7%) Recurrent pneumonia had highest
      sensitivity (50%) but had lowest specificity (31%) among other presenting
      symptoms. All the other symptoms had high specificity (82.8-100%). Dysphagia,
      hyperreactive airway and apnea were the presenting symptoms with high positive
      predictability (100%, 80%, and 75% respectively). We suggest that all children
      who have a history of dysphagia, hyperreactive airway and apnea should be
      evaluated for GER.

PMID- 7823007
TI  - Two dimensional echocardiographic measurement of the pulmonary arteries in
      patients with tetralogy of Fallot angiographic correlation and therapeutic
      implications.

PMID- 7823008
TI  - Spontaneous closure of small ventricular septal defect first six months of life.
AB  - This study was designed to determine the incidence, types of the defects and the
      rate of spontaneous closure of the small ventricular septal defect (VSD) in
      infants who were born at Ramathibodi Hospital during the one year period April 1,
      1991 to March 31, 1992. The diagnosis was confirmed by 2D-echocardiogram and
      Doppler and color flow imaging. RESULT: During the study period, the 15 infants
      diagnosed with small VSD, an incidence of 1.95 per 1,000 livebirths. The male to
      female ratio was 9 to 6. There were 11 muscular and 4 membranous VSD. Small VSD
      had a maximal diameter of 3 mm. of less. Spontaneous closure occurred in 9 to 15
      (60%) during 6 months follow-up. The small muscular VSD spontaneously closed in 9
      of 11 (82%) patients. CONCLUSION: This data supports the previous studies that
      the rate of spontaneous closure of small VSD is high and the muscular defect has
      a higher incidence of spontaneous closure.

PMID- 7823009
TI  - Histiocytoses in children: analysis of 120 cases and the bone marrow findings in
      infection-induced hemophagocytic syndrome vs malignant histiocytosis.
AB  - Retrospective analysis of childhood histiocytoses treated at the Department of
      Pediatrics, Ramathibodi Hospital from May 1970 till June 30, 1992 to verify the
      prevalence according to the recent classification, course and prognosis was
      conducted. Among 120 cases, 54 were Class I or Langerhan Cell Histiocytosis (LCH,
      previously called Histiocytosis-X). Nineteen cases were Class II: Infection
      Associated Hemophagocytic Syndrome (IAHS) and Sinus Histiocytosis. Forty-seven
      cases were class III which included acute monocytic leukemia, juvenile CML;
      malignant histiocytosis, HMR, and histiocytic lymphoma. Excellent prognosis
      (cure) was seen in all cases of Hand-Schuller Christian Disease, eosinophilic
      granuloma, sinus histiocytosis with massive lymphadenopathy and many cases of
      Class II (except IAHS). The worse prognosis (100% mortality rate) was seen in HMR
      and juvenile CML. The intermediate prognosis (50%, 54%, 58.8% and 66.7% mortality
      rate) was seen in MH, HL, LSD and IAHS respectively. To differentiate between
      IAHS and MH/HMR, the prominent bone marrow findings in 12 cases of IAHS revealed
      that every case showed prominent hemophagocytosis by the promono
      histiocytes/histiocytes, the maximal total erythroblasts (TE) were only 7.5 per
      cent except for 3 cases; in which one case with agranulocytosis from co
      trimoxazole had 84 per cent erythroid cells, one case with prior co-trimoxazole
      treatment had 37 per cent TE, the last one had 40 per cent TE with massive GI
      bleeding while in the recovery stage of DHF. All 5 cases of HMR had prominent
      hemophagocytosis and increased TE (> 22%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7823010
TI  - Thrombotic risk of children with thalassemia.
AB  - Pulmonary microthromboembolism is one of the serious complications found in
      patients with thalassemia. The pathogenesis is undetermined. The thrombotic risk
      in 44 patients (26 males, 18 females) with beta-thalassemia/hemoglobin E disease
      and without clinical symptoms of thrombosis were studied. The age ranged from 3
      19 yr (X +/- SD = 10 +/- 4). Neither of them had chronic hepatitis B infection.
      They were divided into three groups according to clinical manifestations as
      follows: (1) Mild form (n = 12). They did not require blood transfusion. The mean
      +/- SD of hematocrit was 23.3 per cent +/- 2.3; (2) Severe form (n = 19). They
      required frequent blood transfusion. The mean +/- SD of hematocrit was 17.7 per
      cent +/- 1.5; (3) Severe form with splenectomy (n = 13). They seldom required
      blood transfusion. The mean +/- SD of hematocrit was 21.8 per cent +/- 3.5. Most
      of the patients had delayed growth. They had high serum ferritin reflecting iron
      overload status which was prominent in the severe groups (group 2 & 3). The
      prothrombin time and serum albumin were slightly decreased, and the serum alanine
      transaminase were slightly increased; all of which reflected mild alteration of
      liver function. The plasma AT III, PC and PS antigen in the three groups were
      similar. The mean +/- SD of AT III antigen was 106.7 per cent +/- 22.2 which is
      normal. The mean +/- SD of PC antigen was 44.2 per cent +/- 14.2 and PS antigen
      level was 77.2 per cent +/- 17.8.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7823011
TI  - Chemotherapy in patients with retinoblastoma.
AB  - Chemotherapy composed of vincristine, cyclophosphamide, procarbazine and
      intrathecal thiotepa/methotrexate (in the indicated ones) were given for 1.5
      years in the doubtful and very unfavorable (Reese-Ellsworth classification) cases
      of retinoblastoma. There were 58 new cases treated at the Department of
      Ophthalmology and the Department of Pediatrics, Ramathibodi Hospital from October
      1, 1985 to December 31, 1991. Eight cases had refused the surgery prior to
      admission. Nine cases were not given chemotherapy due to the very advanced cases
      and refusal. Forty-nine cases received chemotherapy. Eighteen cases were not
      followed. Among 31 evaluable cases, three cases had progression of the disease.
      Twenty-eight cases (90%) were clinically well 2 months-6 years after
      discontinuation of chemotherapy. The good result could be attributable to
      spontaneous regression (minimal percentage), surgery, radiation therapy or
      chemotherapy. However, obvious chemotherapeutic effects were seen in some cases.
      Even though 28 cases seemed to have good result including three of the 8 cases
      who had refused surgery before admission, we should stress that retinoblastoma is
      a curable disease provided that early diagnosis and treatment are rendered.
      Ophthalmologic examination in first degree relatives should be done in the
      bilaterally involved cases.

PMID- 7823012
TI  - Blood levels of diazepam after single rectal administration in children.

PMID- 7823013
TI  - Care of Thai hemophilia patients from 1969 to 1991.

PMID- 7823014
TI  - Coupling as a way of life.

PMID- 7823015
TI  - y(+)-type cationic amino acid transport: expression and regulation of the mCAT
      genes.
AB  - The transport of cationic amino acids across animal cell membranes is largely
      mediated by a small group of well-described transport system (y+, bo,+, Bo,+).
      Only recently have genes encoding transport proteins in some of these systems
      been isolated. Two genes, mCAT-1 and mCAT-2, encode related multiple membrane
      spanning proteins that share substantial amino acid sequence identity and
      virtually superimposable hydrophilicity profiles. mCAT-1 and mCAT-2 proteins
      expressed in Xenopus oocytes are functionally indistinguishable and similar to
      transport system y+, but have distinct tissue distribution patterns. mCAT-1
      expression is nearly ubiquitous and produces a single protein, while mCAT-2 is
      highly tissue-specific, has two distinct protein isoforms encoded by a single
      gene and is expressed in different tissues using at least two widely separated
      promoters. All three proteins facilitate the ion-independent transport of
      arginine, lysine and ornithine. Both mCAT-1 and mCAT-2 proteins have low amino
      acid sequence similarity but strikingly similar hydrophilicity profiles with
      amino acid antiporters, uniporters and symporters of yeast, fungi and eubacteria.
      Current work will elucidate whether any of the mCAT proteins interact with
      members of a newly identified family of single membrane-spanning proteins, such
      as rBAT, 4F2 and NAA-Tr, which are thought to modulate or activate y+L and/or
      bo,+ transport systems.

PMID- 7823016
TI  - A new family of proteins (rBAT and 4F2hc) involved in cationic and zwitterionic
      amino acid transport: a tale of two proteins in search of a transport function.
AB  - The currently identified cDNA clones of mammalian amino acid transporters can be
      grouped into five different families. One family is composed of the proteins rBAT
      and the heavy chain (hc) of the cell surface antigen 4F2. RNAs encoding these two
      proteins induce a system b(o,+)-like (rBAT) and a system y+L-like (4F2hc)
      activity in Xenopus oocytes. Surprisingly, rBAT and 4F2hc do not seem to be pore
      forming proteins. This finding supports the hypothesis that rBAT and 4F2hc are
      subunits or modulators of the corresponding amino acid transport systems.
      Expression of rBAT in oocytes induces high-affinity transport of cystine, which
      is shared with transport of cationic and zwitterionic amino acids. The rBAT gene
      is expressed mainly in kidney and small intestine. The rBAT protein is localized
      to the microvilli of proximal straight tubules of the kidney and mucosa from the
      small intestine. This finding is consistent with the involvement of rBAT in a
      high-affinity resorption system for cystine in the proximal straight tubule of
      the nephron. All of these characteristics suggest that rBAT is a good candidate
      for a cystinuria gene. Cystinuria is an inheritable defect in high-affinity
      transport of cystine, shared with cationic amino acids, through epithelial cells
      of the renal tubule and intestinal tract. Very recently, point missense mutations
      have been found in the rBAT gene of cystinuria patients. The most frequent rBAT
      mutation, M467T (threonine substitution of methionine at residue 467) nearly
      abolished the amino acid transport activity elicited by rBAT in oocytes. This
      result offers convincing evidence that rBAT is a cystinuria gene. Biochemical,
      cytological and genetic approaches are now needed to delineate the mechanism of
      action of rBAT and 4F2hc in the transport of amino acids.

PMID- 7823017
TI  - Metamorphosis of research on ion-coupled metabolite transport.

PMID- 7823018
TI  - Structure, function and evolution of solute transporters in prokaryotes and
      eukaryotes.
AB  - In both prokaryotes and eukaryotes, transport systems of organic solutes can be
      classified as passive transporters, such as channels and facilitated
      transporters, and active transporters, which utilize diverse energy-coupling
      mechanisms. In the past decade, our understanding of the biochemistry and
      molecular biology of transporters from Escherichia coli has progressed
      significantly, whereas the analysis of mammalian transporters has initially been
      limited by the ability to purify membrane proteins. The recent development of
      methods to detect the activity of recombinant proteins in individual cells,
      however, has led to the cloning of several novel mammalian transporter cDNAs. One
      of the most useful expression cloning systems is Xenopus oocytes in conjunction
      with uptake studies and electrophysiological experiments. Overall, the sequence
      information and the functional data derived from many transporters has revealed
      unifying designs, similar energy-coupling mechanisms and common evolutionary
      origins. Here, I will provide a general survey of the known transport systems in
      bacteria, yeast, plants, insects and vertebrates and illustrate the different
      types of transport systems in mammals by discussing transporters recently studied
      in our laboratory.

PMID- 7823019
TI  - Ca2+ transport in Saccharomyces cerevisiae.
AB  - Cytosolic free Ca2+ is maintained at submicromolar levels in budding yeast by the
      activity of Ca2+ pumps and antiporters. We have recently identified the
      structural genes for two Ca2+ pumps, PMC1 [correction of PCM1] and PMR1, which
      are required for Ca2+ sequestration into the vacuole and secretory organelles,
      respectively. The function of either Ca2+ pump is sufficient for yeast viability,
      but deletion of both genes is lethal because of elevation of cytosolic [Ca2+] and
      activation of calcineurin, a Ca(2+)- and calmodulin-dependent protein
      phosphatase. Calcineurin activation decreases Ca2+ sequestration in the vacuole
      by a putative Ca2+ antiporter and may also increase Ca2+ pump activity. These
      regulatory processes can affect the ability of yeast strains to tolerate high
      extracellular [Ca2+]. We propose a model in which the cellular response to
      changes in the environmental levels of Ca2+ is mediated by calmodulin and
      calcineurin which, in turn, modulate the various types of Ca2+ transporters.

PMID- 7823020
TI  - Renal and small intestinal sodium-dependent symporters of phosphate and sulphate.
AB  - Homeostasis of inorganic phosphate (P(i)) and sulphate (Si) is largely achieved
      by absorption in the mammalian small intestine and by reabsorption in the
      proximal tubule of the kidney. Under normal physiological conditions, the kidney
      appears to play the major role in maintaining the extracellular concentration of
      these anions. In both epithelia, reabsorption of P(i) and to some extent also of
      Si underlie a variety of regulatory acute and chronic control mechanisms. Acute
      regulatory mechanisms are predominantly found in renal P(i) reabsorption, whereas
      chronic regulation of transepithelial P(i) transport is observed in both tissues.
      Also, in both epithelia, apically located sodium-dependent transport systems
      (Na+/P(i) and Na+/Si symport) represent major targets for known regulatory
      factors. By expression cloning using oocytes of Xenopus laevis, renal and small
      intestinal Na(+)-dependent phosphate and sulphate transport systems have been
      identified. Evidence has been obtained that cloned Na+/P(i) and Na+/Si symporters
      are localized in the apical membrane of proximal tubular or small intestinal
      epithelial cells respectively. Furthermore, recent results indicate that one of
      the cloned Na+/P(i) symporters is involved in the physiological and
      pathophysiological regulation of proximal tubular P(i) reabsorption.

PMID- 7823021
TI  - The lactose permease meets Frankenstein.
AB  - The lactose permease (lac) of Escherichia coli is a paradigm for membrane
      transport proteins. Encoded by the lacY gene, the permease has been solubilized,
      purified to homogeneity, reconstituted into phospholipid vesicles and shown to
      catalyse the coupled translocation of beta-galactosides and H+ with a
      stoichiometry of unity. Circular dichroism and other spectroscopic approaches
      demonstrate that the purified permease is about 80% helical. Based on hydropathy
      analysis of the primary amino-acid sequence, a secondary structure has been
      proposed in which the protein has 12 hydrophobic domains in alpha-helical
      conformation that traverse the membrane in zigzag fashion connected by
      hydrophilic loops. A variety of other approaches are consistent with the model
      and demonstrate that both the N and C termini are on the inner surface of the
      membrane, and studies on an extensive series of lac permease/alkaline phosphatase
      fusion proteins provide exclusive support for the topological predictions of the
      12-helix motif. This presentation concentrates on the use of site-directed
      fluorescence spectroscopy to study structure-function relationships in the
      permease.

PMID- 7823022
TI  - 'Active' sugar transport in eukaryotes.
AB  - Sugar transporters in prokaryotes and eukaryotes belong to a large family of
      membrane proteins containing 12 transmembrane alpha-helices. They are divided
      into two classes: one facilitative (uniporters) and the other concentrative
      (cotransporters or symporters). The concentrative transporters are energised by
      either H+ or Na+ gradients, which are generated and maintained by ion pumps. The
      facilitative and H(+)-driven sugar transporters belong to a gene family with a
      distinctive secondary structure profile. The Na(+)-driven transporters belong to
      a separate, small gene family with no homology at either the primary or secondary
      structural levels. It is likely that the Na(+)- and H(+)-driven sugar
      cotransporters share common transport mechanisms. To explore these mechanisms, we
      have expressed cloned eukaryote Na+/sugar cotransporters (SGLT) in Xenopus laevis
      oocytes and measured the kinetics of sugar transport using two-electrode voltage
      clamp techniques. For SGLT1, we have developed a six-state ordered model that
      accounts for the experimental data. To test the model we have carried out the
      following experiments. (i) We measured pre-steady-state kinetics of SGLT1 using
      voltage-jump techniques. In the absence of sugar, SGLT1 exhibits transient
      carrier currents that reflect voltage-dependent conformational changes of the
      protein. Time constants for the carrier currents give estimates of rate constants
      for the conformational changes, and the charge movements, integrals of the
      transient currents, give estimates of the number and valence of SGLT1 proteins in
      the plasma membrane. Ultrastructural studies have confirmed these estimates of
      SGLT1 density. (ii) We have perturbed the kinetics of the cotransporter by site
      directed mutagenesis of selected residues.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7823023
TI  - Porters and neurotransmitter transporters.
AB  - Uptake of neurotransmitters involves multiple transporters acting in different
      brain locations under different physiological conditions. The vesicular
      transporters are driven by a proton-motive force generated by a V-ATPase and
      their substrates are taken up via proton/substrate exchange. The plasma membrane
      transporters are driven by an electrochemical gradient of sodium generated by a
      Na+/K(+)-ATPase. Two distinct families of transporters were identified in this
      group. One cotransports sodium with glutamate and other amino acids and requires
      additionally an outwardly directed potassium gradient. The second cotransports
      sodium, chloride and a variety of neurotransmitters, including gamma-aminobutyric
      acid (GABA), glycine and monoamines. Genes and cDNA encoding several members of
      the latter family have been cloned and studied in detail. The structure and
      function as well as the evolutionary relationships among these neurotransmitter
      transporters are discussed.

PMID- 7823024
TI  - Neurotransmitter transporters: three important gene families for neuronal
      function.
AB  - Three distinct gene families encode transporter proteins that aid in temporal and
      spatial buffering of neurotransmitter and neurotransmitter metabolite
      concentrations and allow neurons to cycle and recycle transmitter molecules.
      Analyses of these gene families and their products are likely to enhance
      understanding of the molecular neurobiology of neuronal function and may
      elucidate contributors to the genetic etiologies of neurological and psychiatric
      disease.

PMID- 7823025
TI  - Sodium-coupled neurotransmitter transport: structure, function and regulation.
AB  - The removal of neurotransmitters by their transporters--located in the plasma
      membranes of nerve terminals and glial cells--plays an important role in the
      termination of synaptic transmission. In the last 3 years, many neurotransmitter
      transporters have been cloned. Structurally and functionally they can be divided
      into two groups: glutamate transporters, of which to date three have been cloned,
      couple the flow of glutamate to that of sodium and potassium. The second group of
      transporters includes those for GABA, glycine, taurine, norepinephrine, dopamine
      and serotonin. They are sodium- and chloride-dependent, but do not require
      potassium for function. One of these, the GABAA transporter, encoded by GAT-1, is
      perhaps the best characterized. It has been purified and reconstituted and has a
      molecular mass of around 80 kDa, of which 10-15 kDa is sugar. Amino and carboxyl
      termini (around 50 amino acids each) are not required for function. The
      transporter is protected against proteolysis at multiple sites by GABA, provided
      that the two cosubstrates--sodium and chloride--are present. Several amino acid
      residues that are critical for function have been identified in the GABA
      transporter. These include arginine-69 and tryptophan-222 located in the first
      and fourth putative transmembrane helices, respectively. The first is possibly
      involved in the binding of chloride. The tryptophan appears to serve as a binding
      site for the amino group of GABA.

PMID- 7823026
TI  - Biochemistry and molecular biology of the vesicular monoamine transporter from
      chromaffin granules.
AB  - Prior to secretion, monoamines (catecholamines, serotonin, histamine) are
      concentrated from the cytoplasm into vesicles by vesicular monoamine transporters
      (VMAT). These transporters also carry non-physiological compounds, e.g. the
      neurotoxin methyl-4-phenylpyridinium. VMAT acts as an electrogenic antiporter
      (exchanger) of protons and monoamines, using a proton electrochemical gradient.
      Vesicular transport is inhibited by specific ligands, including tetrabenazine,
      ketanserin and reserpine. The mechanism of transport and the biochemistry of VMAT
      have been analyzed with the help of these tools, using mainly the chromaffin
      granules from bovine adrenal glands as a source of transporter. Although
      biochemical studies did not suggest a multiplicity of VMATs, two homologous but
      distinct VMAT genes have recently been cloned from rat, bovine and human adrenal
      glands. The VMAT proteins are predicted to possess 12 transmembrane segments,
      with both extremities lying on the cytoplasmic side. They possess N-glycosylation
      sites in a putative luminal loop and phosphorylation sites in cytoplasmic
      domains. In rat, VMAT1 is expressed in the adrenal gland whereas VMAT2 is
      expressed in the brain. In contrast, we found that the bovine adrenal gland
      expressed both VMAT1 and VMAT2. VMAT2 corresponds to the major transporter of
      chromaffin granules, as shown by partial peptidic sequences of the purified
      protein and by a pharmacological analysis of the transport obtained in
      transfected COS cells (COS cells are monkey kidney cells possessing the ability
      to replicate SV-40-origin-containing plasmids). We discuss the possibility that
      VMAT1 may be specifically addressed to large secretory granules vesicles, whereas
      VMAT2 may also be addressed to small synaptic vesicles; species differences would
      then reflect the distinct physiological roles of the small synaptic vesicles in
      the adrenal gland.

PMID- 7823027
TI  - Molecular physiology of norepinephrine and serotonin transporters.
AB  - Cocaine- and antidepressant-sensitive norepinephrine and serotonin transporters
      (NETs and SERTs) are closely related members of the Na+/Cl- transporter gene
      family, whose other members include transporters for inhibitory amino acid
      transmitters, neuromodulators, osmolytes and nutrients. Availability of cloned
      NET and SERT cDNAs has permitted rapid progress in the definition of cellular
      sites of gene expression, the generation of transporter-specific antibodies
      suitable for biosynthetic and localization studies, the examination of structure
      function relationships in heterologous expression systems and a biophysical
      analysis of transporter function. In situ hybridization and immunocytochemical
      studies indicate a primary expression of NET and SERT genes in brain by
      noradrenergic and serotonergic neurons, respectively. Both NET and SERT are
      synthesized as glycoproteins, with multiple glycosylation states apparent for
      SERT proteins in the brain and periphery. N-glycosylation of NET and SERT appears
      to be essential for transporter assembly and surface expression, but not for
      antagonist binding affinity. Homology cloning efforts have revealed novel NET and
      SERT homologs in nonmammalian species that are of potential value in the
      delineation of the precise sites for substrate and antagonist recognition,
      including a Drosophila melanogaster SERT with NET-like pharmacology.
      Electrophysiological recording of human NETs and SERTs stably expressed in HEK
      293 cells reveals that both transporters move charge across the plasma membrane
      following the addition of substrates; these currents can be blocked by NET-and
      SERT-selective antagonists as well as by cocaine.

PMID- 7823029
TI  - Special transport and neurological significance of two amino acids in a
      configuration conventionally designated as D.
AB  - We point out an ability of certain amino acids to be recognized at a biological
      receptor site as though their amino group bore, instead of an alpha relationship
      to a carboxylate group, a beta, gamma or delta relationship to the same or a
      second carboxylate group. For aspartate, the unbalanced position of its amino
      group between a pair of carboxylates allows its occasional biorecognition as a
      beta-rather than as an alpha-amino acid, whereas for proline and its homologs,
      their cyclic arrangement may allow the imino group, without its being replicated,
      to be sensed analogously as falling at either of two distances from the single
      carboxylate group. The greater separation might allow proline to be seen as
      biologically analogous to gamma-aminobutyric acid. This more remote positioning
      of the imino group would allow the D-form of both amino acids to present its
      amino group in the orientation characteristic of the natural L-form. The dual
      modes of recognition should accordingly be signalled by what appears to be low
      stereospecificity, actually due to a distinction in the enantiorecognition of the
      two isomers. Competing recognition for transport between their respective D- and
      L-forms, although it does not prove that phenomenon, has been shown for proline
      and, significantly, even more strongly for its lower homolog, 2-azetidine
      carboxylate. Such indications have so far revealed themselves rather
      inconspicuously for the central nervous system binding of proline, reviewed here
      as a possible feature of a role suspected for proline in neurotransmission.

PMID- 7823028
TI  - Structure, function and brain localization of neurotransmitter transporters.
AB  - We studied four different cDNAs encoding GABA transporters and three different
      cDNAs encoding glycine transporters in mouse and rat brains. A genomic clone of
      two of the glycine transporters (GLYT1a and GLYT1b) revealed that they derive
      from differential splicing of a single gene. The third glycine transporter
      (GLYT2) is encoded by a separate gene. Antibodies were raised against seven of
      these neurotransmitter transporters and their cytochemical localization in the
      mouse brain was studied. In general, we observed a deviation from the classical
      separation of neuronal and glial transporters. It seems that each of the
      neurotransmitter transporters is present in specific places in the brain and is
      expressed in a different way in very specific areas. For example, the GABA
      transporter GAT4, which also transports beta-alanine, was localized to neurons.
      However, GAT1, which is specific for GABA, was localized not only to neurons but
      also to glial cells. The recently discovered glycine transporter GLYT2 was of
      particular interest because of its deviation from the general structure by a very
      extended N terminus containing multiple potential phosphorylation sites. Western
      analysis and immunocytochemistry in frozen sections of mouse brain demonstrated a
      clear caudal-rostral gradient of GLYT2 distribution, with massive accumulation in
      the spinal cord and brainstem and less in the cerebellum. Its distribution is
      typically neuronal and it is present in processes with varicosities. A
      correlation as observed between the pattern we obtained and that observed
      previously from strychnine binding studies. The results indicate that GLYT2 is
      involved in the termination of glycine neurotransmission at the classical
      inhibitory system in the hindbrain. The availability of four different GABA
      transporters made it possible to look for specific binding sites upon the
      neurotransmitter transporters. An extensive program of site-directed mutagenesis
      led us to identify a potential neurotransmitter binding site on the GABA
      transporters.

PMID- 7823030
TI  - Cation antiports of animal plasma membranes.

PMID- 7823031
TI  - Role of the invertebrate electrogenic 2Na+/1H+ antiporter in monovalent and
      divalent cation transport.
AB  - In recent years, an electrogenic 2Na+/1H+ antiporter has been identified in a
      variety of invertebrate epithelial brush-border membranes of gut, kidney and gill
      tissues. The antiporter differs significantly in its physiological properties
      from the electroneutral 1Na+/1H+ antiporter proposed for vertebrate cells. In all
      invertebrate cells examined, the antiporter displayed a 2:1 transport
      stoichiometry, responded to an induced transmembrane potential and exhibited a
      high binding affinity for the divalent cation Ca2+, which acted as a competitive
      inhibitor of Na+ transport. A monoclonal antibody specific for the crustacean
      electrogenic antiporter inhibited 2Na+/1H+ exchange, but was without effect on
      Na(+)-dependent D-glucose transport. Immunoreactivity was localized at
      hepatopancreatic brush-border and vacuolar membranes, antennal gland coelomosac
      podocytes and posterior gill epithelial cells-all locations were published
      reports described unique cation exchange kinetics. Significant fractions of Ca2+
      transport into invertebrate cells across brush-border membranes occurred by an
      electrogenic, amiloride-sensitive exchange process, probably by the 2Na+/1H+
      antiporter, and this transport was markedly inhibited by exogenous zinc and
      cadmium. A recently identified electroneutral, amiloride-sensitive,
      hepatopancreatic epithelial basolateral Na+/H+ antiporter was uninfluenced by the
      brush-border monoclonal antibody, exhibited an apparent 1:1 transport
      stoichiometry and possessed a minimal divalent cation specificity. Calcium
      transport at this epithelial pole occurred by the combination of a Ca2+/Na+
      antiporter, an ATP-dependent Ca(2+)-ATPase and a verapamil-sensitive calcium
      channel. These crustacean brush-border and basolateral transporters may play
      significant roles in calcification and heavy metal detoxification.

PMID- 7823032
TI  - Molecular structure and regulation of vertebrate Na+/H+ exchangers.
AB  - Na+/H+ exchangers (NHE), also called antiporters, are vital transmembrane
      transporters involved in multiple cellular functions including the regulation of
      intracellular pH, the control of cell volume and transepithelial ion transport.
      These transporters are highly regulated by a remarkably wide variety of stimuli
      which can modulate their expression level and activity. Five isoforms of Na+/H+
      exchangers have been cloned and characterized to date; they define a new gene
      family of vertebrate transporters. These isoforms share the same overall
      structure but exhibit differences with respect to amiloride-sensitivity, cellular
      localization, kinetic variables, regulation by various stimuli and plasma
      membrane targeting in polarized epithelial cells. Biochemical techniques and
      molecular genetics tools provide the means of analyzing these transporters at the
      molecular level. The purpose of this manuscript is to give an overview of the
      main features of the Na+/H+ exchangers with emphasis on recent advances in
      comprehension of the structure-function relationship and regulation mechanisms of
      the ubiquitous isoform: NHE-1.

PMID- 7823033
TI  - Unique permeability barrier of the apical surface of parietal and chief cells in
      isolated perfused gastric glands.
AB  - Although many factors can influence intracellular pH (pHi), some of the most
      important are those that involve the movement of acids and bases across the cell
      membrane. We will discuss recent results concerning barriers to the movement of
      H+, NH3 and CO2 across the apical cell membranes of gastric gland cells. Cell
      membranes are generally highly permeable to small, lipophilic molecules such as
      NH3 and CO2. In fact, only two examples are known of membranes relatively
      impermeable to NH3 and none membranes permeable to CO2. We recently developed a
      technique for perfusing the lumen of a single hand-dissected gastric gland on the
      stage of a microscope, while monitoring pHi with a fluorescent dye. We observed
      the expected pHi changes when we exposed the basolateral (i.e. blood-side)
      membrane to a pH 6.4 solution (a large, rapid pHi decrease), to a pH 7.4 solution
      containing approximately 0.3 mmoll-1 NH3 (a large and rapid pHi increase) or to a
      pH7.4 solution equilibrated with 1% CO2 (a rapid pHi decrease of -0.08). However,
      pHi was not significantly affected by perfusing the lumen with a pH 1.4 solution,
      with a pH 7.4 solution containing as much as 2.7 mmoll-1 NH3 or with a pH 6.1
      solution equilibrated with 100% CO2. These data indicate that a barrier at or
      near the apical membrane has a uniquely low permeability to H+, NH3 and CO2.

PMID- 7823034
TI  - K+/H+ antiport in the tobacco hornworm midgut: the K(+)-transporting component of
      the K+ pump.
AB  - The midgut of the tobacco hornworm secretes K+ across the apical plasma membrane
      of its goblet cells. This secondary K+ transport results from K+/H+ antiport
      energized by the proton-motive force generated by a primary, H(+)-transporting
      plasma membrane V-ATPase. Thus, the lepidopteran midgut constitutes a well
      established example of the emerging concept that the proton-motive force is an
      alternative to the classical sodium-motive force for the energization of animal
      plasma membranes. K+/H+ antiport in the tobacco hornworm midgut is
      electrophoretic, exchanging 2H+ for 1K+. Under physiological conditions, it is
      energized by the voltage component of the proton-motive force. The strong
      coupling of electrophoretic K+/2H+ antiport with the electrogenic V-ATPase
      provides, in principle, the minimal device for the alkalization of the midgut
      lumen to pH values higher than 11. K+/H+ antiport is insensitive to bafilomycin
      A1, but is inhibited by amiloride or Concanavalin A. Lectin staining of blots
      after SDS-PAGE revealed several glycosylated polypeptides in the goblet cell
      apical membrane which are not part of the V-ATPase and thus are candidates for
      the antiporter protein. Current efforts are focused on the isolation of the K+/H+
      antiporter.

PMID- 7823035
TI  - Na+/Ca2+ antiport in the mammalian heart.
AB  - The cardiac Na+/Ca2+ antiporter moves 3 Na+ across the plasma membrane in
      exchange for a single Ca2+ moving in the opposite direction. It is the principal
      Ca2+ efflux mechanism in myocardial cells; however, it also contributes to Ca2+
      influx under certain conditions. It is particularly abundant in the heart, but is
      also expressed in other tissues such as smooth and skeletal muscle, the kidney
      and the brain. The cardiac antiporter itself is a protein of 938 amino acids,
      with a cleaved NH2-terminal signal sequence, 11 putative transmembrane segments
      and a large hydrophilic domain of 520 amino acids between the fifth and sixth
      transmembrane segments. Alternative mRNA splicing mechanisms generate tissue
      specific isoforms in a limited region within the hydrophilic domain. Most of the
      hydrophilic domain can be deleted without altering the kinetics of the transport
      reaction; the regulatory properties of the antiporter are markedly affected by
      this deletion however. Two different modes of regulation of antiport activity
      have been characterized and appear to involve two different inactive states of
      the carrier. The first is promoted by the presence of cytosolic Na+ in the
      absence of ATP and the second is promoted by the absence of cytosolic Ca2+. ATP
      dependent regulation of antiport activity may involve interactions with the
      cellular cytoskeleton, since the effects of ATP depletion can be mimicked by
      cytochalasin D. Ca(2+)-dependent regulation of antiport activity appears to
      involve the interaction of cytosolic Ca2+ with two acidic amino acid sequences
      within a limited region of the hydrophilic domain.

PMID- 7823036
TI  - Na+/H+ antiport: modulation by ATP and role in cell volume regulation.
AB  - Na+/H+ antiport is a major determinant of intracellular pH (pHi) and also plays
      an important role in the maintenance of cellular volume. Na+/H+ exchange through
      NHE-1, the ubiquitous isoform of the antiporter, is accelerated by cytosolic
      acidification and also by osmotically induced cell shrinking, thereby promoting
      recovery of the physiological pHi and volume, respectively. Although hydrolysis
      of ATP is not required for transport of ions through the antiporter, metabolic
      depletion exerts a marked inhibitory effect. Depletion of ATP also prevents
      osmotic activation and volume regulation. Contrary to earlier suggestions,
      however, changes in the phosphorylation state of the antiporter itself are not
      involved in the effects of either metabolic depletion or osmotic stimulation.
      Nevertheless, the cytosolic carboxy-terminal segment of the antiporter, which
      contains the major phosphorylation sites, is essential for the ATP dependence as
      well as for osmotic activation. It is conceivable that this domain interacts with
      ancillary phosphorylated or nucleotide-binding proteins, with the cytoskeleton
      and/or with specific phospholipids, which modulate the rate of transport.
      Nucleotide dependence and osmotic sensitivity have been compared in three
      different isoforms of the antiporter, heterologously expressed in fibroblastic
      cells. Like NHE-1, NHE-2 and NHE-3 were severely inhibited by depletion of ATP.
      In contrast, whereas NHE-2 was stimulated by osmotic shrinkage, NHE-3 was
      inhibited. The possible physiological significance of the ATP-dependence and
      osmotic responsiveness of the antiporter isoforms is discussed.

PMID- 7823037
TI  - Endosomal accumulation of pH indicator dyes delivered as acetoxymethyl esters.
AB  - Intracellular distributions of the putative cytosolic pH indicator dyes BCECF
      [2',7'-bis-(2-carboxyethyl)-5(and 6)-carboxyfluorescein], C.SNARF [5(and 6)
      carboxy-seminaphthorhodafluor-1], and C.SNARF-calcein have been examined in
      Neurospora crassa and in murine fibroblasts (NIH-3T3 cells) under conditions in
      which both kinds of cells produce visible microscopic vacuoles. All three dyes
      were administered in electroneutral forms, with the hydroxyl and carboxyl groups
      esterified (designated as -AM esters). As judged qualitatively from fluorescence
      levels, hydrolytic derivatives of the two heavily esterified dyes (BCECF-AM and
      C.SNARF-calcein-AM) accumulated in the vacuoles after exposures of approximately
      15 min or more, while the simpler dye (C.SNARF-AM) and its derivatives were
      almost excluded from visible vacuoles. Fluorescence from this dye, alone among
      the three, also washed out of Neurospora rapidly upon removal of extracellular
      dye. There was no evidence for stable accumulation of any of the dyes in cytosol
      per se. For BCECF(-AM), comparison of the distribution of fluorescence with the
      size distribution of vacuoles in Neurospora strongly suggests that the dyes are
      also accumulated by endomembranal vesicles (EMVs) which lie below the limit of
      resolution in the light microscope, and the same inference can be drawn for the
      fibroblasts. Uptake of -AM dyes by EMVs, including frank vacuoles, probably
      results from the action of intravesicular esterases, following diffusional entry
      of lipophilic neutral molecules or partially de-esterified anions. Calculations
      of actual cytosolic pH values, or even changes of pH, based on intracellular
      fluorescence of these dyes, clearly depend upon quantitative knowledge of the
      subcellular dye distribution. Therefore, until the problem is reliably solved of
      how to visualize submicroscopic vesicles in living cells, the safest approach to
      the use of BCECF, C-SNARF and their congeners for cytosolic pH measurement would
      be to devise methods for coaxing uptake of the ionic forms of these dyes and to
      abandon use of the esterified forms.

PMID- 7823038
TI  - Bacterial and plant antiporters.

PMID- 7823039
TI  - Molecular physiology of the Na+/H+ antiporter in Escherichia coli.
AB  - All living cells maintain an inwardly directed Na+ gradient and a constant
      intracellular pH. Na+/H+ antiporters have been assigned an essential role in
      these homeostatic mechanisms in all cells. In Escherichia coli, two Na+/H+
      antiporter genes, nhaA and nhaB, have been cloned. Deletion of either one or both
      showed that NhaA is essential for adaptation to high salinity, for growth at
      alkaline pH in the presence of Na+ and for challenging Li+ toxicity. NhaB confers
      tolerance to low levels of Na+ and becomes essential when the activity of NhaA
      limits growth. The adaptive response to Na+ is mediated by the positive regulator
      nhaR, which transduces the signal (intracellular Na+) to expression of the nhaA
      gene. We have identified Glu-134 of NhaR as part of the 'Na+ sensor' of NhaA. In
      agreement with the role of NhaA in pH homeostasis, its Na(+)-dependent expression
      is enhanced at alkaline pH. Reconstitution of pure NhaA and NhaB in
      proteoliposomes demonstrates that, whereas both are electrogenic (the H+/Na+
      stoichiometry of NhaA is 2), only NhaA is pH-dependent, increasing its activity
      1000-fold between pH 7 and 8.5. Mutating all the histidines of NhaA shows that
      His-226 is part of the 'pH sensor' of NhaA.

PMID- 7823040
TI  - The role of monovalent cation/proton antiporters in Na(+)-resistance and pH
      homeostasis in Bacillus: an alkaliphile versus a neutralophile.
AB  - Both neutralophilic Bacillus subtilis and alkaliphilic Bacillus firmus OF4 depend
      upon electrogenic Na+/H+ antiporters, which are energized by the gradients
      established by respiration-coupled proton extrusion, to achieve Na(+)-resistance
      and pH homeostasis when the external pH is very alkaline. The interplay of proton
      and sodium cycles is discussed. In B. subtilis, pH homeostasis, up to pH9, can be
      achieved using K+ when Na+ is unavailable or when the gene encoding the Na+/H+
      antiporter that is involved in Na(+)-dependent pH homeostasis is disrupted. That
      gene is a member of the tetracycline efflux family of genes. A second gene,
      encoding a Na+/H+ antiporter that functions in Na(+)-resistance, has been
      identified, and candidates for the K+/H+ antiporter genes are under
      investigation. Aggregate Na+/H+ antiport activity in B. subtilis is as much as 10
      times lower than in the alkaliphile, and the neutralophile cannot regulate its
      internal pH upon a shift to pH 10.5. Upon such a shift, there is a pronounced
      reduction in the generation of a primary electrochemical proton gradient. The
      alkaliphile, by contrast, maintains substantial driving forces and regulates its
      internal pH in an exclusively Na(+)-coupled manner upon shifts to either pH 8.7
      or 10.5. One gene locus has been identified and a second locus has been inferred
      as encoding relevant antiporter activities.

PMID- 7823041
TI  - Bacterial anion exchange: reductionist and integrative approaches to membrane
      biology.
AB  - Studies of two different bacterial anion exchange proteins (antiporters) led us
      to conclude that both reductionist and integrative approaches contribute to
      progress in understanding membrane biology. We have used a reductionist
      perspective in applying cysteine scanning mutagenesis to probe individual amino
      acid positions of UhpT (uptake of hexose phosphate transporter), the carrier
      responsible for transport of glucose 6-phosphate by Escherichia coli. This work
      has established experimental criteria that should allow one to identify and
      localize the translocation pathway in such membrane proteins. An integrative view
      is exemplified by work with OxlT (oxalate transporter), the carrier used by an
      anaerobe Oxalobacter formigenes to catalyze the antiport of divalent oxalate and
      monovalent formate. The activity of OxlT is functionally coordinated with that of
      a cytosolic oxalyl decarboxylase; together, these vectorial and scalar activities
      constitute a metabolic proton pump, allowing O. formigenes to display
      decarboxylative phosphorylation. The role played by OxlT argues that membrane
      carriers can assume unanticipated emergent properties when their biochemical
      functions are properly articulated in relation to other aspects of cell function.

PMID- 7823042
TI  - Hexose/H+ symporters in lower and higher plants.
AB  - A well-studied transporter of plant cells is the hexose/H+ symporter of the
      unicellular alga Chlorella kessleri. Its properties, studied in vivo, are briefly
      summarized. In part, they are atypical and it has been suggested that this porter
      acts in an asymmetric way. Three genes coding for Chlorella hexose transport
      activity have been identified (HUP1, HUP2 and HUP3). HUP1 cDNA expressed in a
      mutant of Schizosaccharomyces pombe not transporting any D-glucose has been
      studied in detail. Several mutants with changed Km values for substrate were
      obtained, some by random polymerase chain reaction mutation and selection for
      decreased sensitivity towards the toxic sugar 2-deoxyglucose, some by site
      directed mutagenesis. The amino acids affected clustered in the centre of the
      putative transmembrane helices V, VII and XI. Large families of hexose
      transporter genes are found in higher plants (Arabidopsis, Chenopodium, Ricinus).
      Their functional role is discussed. Finally, the progress made in studying plant
      transporters in a vesicle system energized by cytochrome c oxidase is summarized.

PMID- 7823043
TI  - Uniporters, symporters and antiporters.

PMID- 7823044
TI  - Gene-product designations for amino acid transporters.
AB  - The molecular cloning of genes that encode amino acid transporters presents the
      scientific community with the opportunity to name their gene products using a
      scheme that could usefully recall the well-defined transport system most similar
      in properties to the newly identified cloned gene product. To avoid the problem
      of rising confusion, we propose to take advantage of established designation
      methods that indicate the types of amino acids transported and the co-substrate
      ion requirement of their transport. The economy obligated by the necessity to
      keep the number of symbols in a gene name to a minimum will rarely permit a
      listing of the full range of substrates, since amino acid transport systems have
      broad substrate specificities with co-substrate requirements that can differ in a
      substrate-specific manner. Hence, the use of established systems to codify groups
      of amino acid transport systems, which allow identification of the substrate
      range by using 1-3 letters, e.g. A, L or even ASC, could be integrated with a
      system used to indicate the ion-dependence of transport. The discoverers of
      transporters are mainly proceeding with commendable reserve and are inviting
      discussion, a desire which this essay urges be facilitated by more formal
      arrangements for further planning. These discoverers have also shown, along with
      an expressed desire for guidance, well-advised spontaneity in making reference to
      the substrate range, two trends that together suggest that a good set of
      designations can evolve that will be highly descriptive.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7823045
TI  - Thermodynamics of symport and antiport catalyzed by cloned or native
      transporters.
AB  - Thermodynamic measurements are required to confirm whether cloned transport
      associated proteins in a membrane truly constitute a functional transport system.
      Symport or antiport, catalyzed by native systems or by cloned proteins in
      membranes, can lead to steady-state intracellular accumulation of solute when the
      electrochemical potentials of activator ion and solute are energetically coupled.
      Secondary active transport can occur if an appropriate physical coupling
      mechanism exists in the membrane. Driving forces for secondary active transport
      are ultimately established by primary active transport or respiration. Steep
      steady-state gradients of solute can be maintained when the ion:solute coupling
      ratio is greater than one and/or when coupling includes an electrical component.
      Although the steady-state accumulation of substrate is independent of the exact
      physical mechanism of transport, non-equilibrium and equilibrium transport
      kinetics aid in interpreting the rate, direction (symport versus antiport) and
      control of ion-coupled flux across a membrane. In some cases, the activator ion's
      chemical gradient alone is energetically adequate to maintain steady-state
      intracellular accumulation of solute, as demonstrated in invertebrate epithelial
      cells. To interpret accumulation ratios accurately, it is necessary to measure
      the intracellular activity coefficients for ions. For example, liquid ion
      exchange microelectrode measurements demonstrate that over 30% of intracellular
      Na+ can be sequestered in epithelial cells.

PMID- 7823046
TI  - Energizing porters by proton-motive force.
AB  - It is generally accepted that the chemistry of water was the most crucial
      determinant in shaping life on earth. Among the more important chemical features
      of water is its dissociation into protons and hydroxyl ions. The presence of
      relatively high proton concentrations in the ambient solution resulted in the
      evolution of proton pumps during the dawn of life on earth. These proton pumps
      maintained neutral pH inside the cells and generated electrochemical gradients of
      protons (proton-motive force) across their membranes. The existence of proton
      motive force enabled the evolution of porters driven by it that are most probably
      among the more primitive porters in the world. The directionality of the
      substrate transport by the porters could be to both sides of the membranes
      because they can serve as proton symporters or antiporters. One of the most
      important subjects of this meeting is the mechanism by which proton-motive and
      other ion-motive forces drive the transport processes through porters. Is there a
      common mechanism of action for all proton-driven porters? Is there some common
      partial reaction by which we can identify the way that porters are energized by
      proton-motive force? Is there a common coupling between proton movement and
      uptake or secretion of certain molecules? Even a partial answer to one of these
      questions would advance our knowledge... or confusion. As my mentor Efraim Racker
      used to say: 'If you are not totally confused you do not understand the issue'.

PMID- 7823047
TI  - Ionic circuit analysis of K+/H+ antiport and amino acid/K+ symport energized by a
      proton-motive force in Manduca sexta larval midgut vesicles.
AB  - Amino acid/K+ symport (cotransport) across a model epithelium, the lepidopteran
      midgut, is energized by an electrogenic H+ V-ATPase (H+ pump) in parallel with an
      electrophoretic K+/H+ antiporter (exchanger). Attempts to analyze this process
      using well-known equilibrium thermodynamic equations (Nernst, Gibbs), diffusion
      equations (Nernst, Planck, Einstein, Goldman, Hodgkin, Katz) and equations based
      on Ohm's law (Hodgkin, Huxley) have all encountered major difficulties. Although
      they are useful for analyzing nerve/muscle action potentials, these state
      equations assume that brief perturbations in membrane conductance, gm, and
      membrane voltage, Vm, occur so rapidly that no other parameters are significantly
      disturbed. However, transport studies often extend for minutes, even for hours.
      Perturbation of one parameter in complex transport systems invariably results in
      a state change as all of the other elements adjust to the prolonged stress. The
      development of a comprehensive mathematical treatment for transport systems that
      contain pumps and porters (transporters) has been hampered by the empirical
      nature of the concept of membrane permeability and conductance. The empirical
      definition of permeability was developed before pumps and porters were known.
      Thus, 'permeability' is a gross parameter that, in practice if not in theory,
      could describe all transport pathways including pumps, porters and channels. To
      surmount these difficulties, we have applied ionic circuit analysis to vesicular
      systems containing insect midgut transport proteins. In this analysis, pumps,
      porters and channels, as well as ionic concentration gradients and membrane
      capacitance, are components of ionic circuits that function to transform
      metabolic energy (e.g. from ATP hydrolysis) into useful metabolic work (e.g.
      amino acid uptake). Computer-generated by an H+ V-ATPase to K+/2H+ antiport and
      amino acid/K+ symport in the lepidopteran midgut.

PMID- 7823048
TI  - Na(+)-independent transport (uniport) of amino acids and glucose in mammalian
      cells.
AB  - Recent advances have made possible the isolation of the genes and their cDNAs
      encoding Na(+)-independent amino acid transporters. Two classes of amino acid
      'uniporters' have been isolated. One class contains the mCAT (murine cationic
      amino acid transporter) gene family that encodes proteins predicted to span the
      membrane 12-14 times and exhibits structural properties similar to the GLUT
      (glucose transporter) family and to other well-known transporters. The other
      class consists of two known genes, rBAT (related to B system amino acid
      transporters) and 4F2hc, that share amino acid sequence similarity with alpha
      amylases and alpha-glucosidases. They are type II glycoproteins predicted to span
      the membrane only once, yet they mediate the Na(+)-independent transport of
      cationic and zwitterionic amino acids in Xenopus oocytes. Mutations in the human
      rBAT gene have been identified by Palacin and his co-workers in several families
      suffering from a heritable form of cystinuria. This important finding clearly
      establishes a key role for rBAT in cystine transport. The two classes of amino
      acid transporters are compared with the well-studied GLUT family of Na(+)
      independent glucose transporters.

PMID- 7823049
TI  - Serial proton magnetic resonance spectroscopy in a patient with the interval form
      of carbon monoxide poisoning.
AB  - Serial proton magnetic resonance spectroscopy (1H-MRS) studies were performed
      from immediately after the appearance of sequelae in a patient with the interval
      form of carbon monoxide (CO) poisoning. The volume of interest was set over the
      frontal lobe white matter. In the early period a persistent increase in choline
      was found, which was thought to reflect the course of progressive demyelination.
      The appearance of lactate and decrease in N-acetylaspartate reflected the point
      at which neuron injury became irreversible. These were followed later by the
      finding of irreversible changes on MRI and single photon emission computed
      tomography. The findings suggest that 1H-MRS may be a useful modality to
      determine neuron viability and prognosis early in the course of the interval form
      of CO poisoning.

PMID- 7823050
TI  - Evidence for increased nitric oxide production in multiple sclerosis.

PMID- 7823051
TI  - Progressive dural venous sinus thrombosis treated with local streptokinase
      infusion.

PMID- 7823052
TI  - Cervical dystonia as an isolated sign of a basal ganglia tumour.

PMID- 7823053
TI  - Debrisoquine hydroxylase gene polymorphism in Parkinson's disease and amyotrophic
      lateral sclerosis.

PMID- 7823054
TI  - Glioependymal cyst of the cerebellopontine angle.

PMID- 7823055
TI  - Double intraspinal enterogenous cysts.

PMID- 7823056
TI  - Craniopharyngioma: early and long term recurrence after partial removal.

PMID- 7823057
TI  - Psychosocial factors in chronicity of epilepsy.

PMID- 7823058
TI  - Spinal somatosensory potential monitoring in three cases of neurological
      deterioration after laminectomy for cervical spondylotic myelopathy.

PMID- 7823059
TI  - Different criteria in the assessment of visuospatial neglect.

PMID- 7823060
TI  - Memory for context but not for content: a neuropsychological follow up.

PMID- 7823061
TI  - Surveying multiple sclerosis in the United Kingdom.

PMID- 7823062
TI  - Multiple sclerosis in island populations: prevalence in the Bailiwicks of
      Guernsey and Jersey.
AB  - The aim of this study was to establish for the first time the prevalence of
      multiple sclerosis in the Bailiwicks of Guernsey and Jersey, as representing the
      most southerly part of the British Isles. All patients with multiple sclerosis in
      the Channel Islands resident on prevalence day were identified by contacting all
      medical practices, Multiple Sclerosis, and Action Research for Multiple Sclerosis
      societies by letter and visits. The crude overall prevalence rates were
      113/100,000 (95% confidence interval (95% CI) 90.3-135.7) and 86.7/100,000 (95%
      CI 63.3-110.0) for the Bailiwicks of Jersey and Guernsey respectively. When
      standardised to the age and sex structure of a previously reported Northern
      Ireland population the standardised prevalence ratios were 120.2/100,000 (95% CI
      96.0-144.3) for Jersey and 95.6/100,000 (95% CI 69.9-121.3) for the Bailiwick of
      Guernsey. When compared with recent studies in the northern United Kingdom the
      prevalence rates for multiple sclerosis in the Channel Islands lend some support
      to the proposed latitudinal gradient in the British Isles although the
      standardised prevalence ratio in the Bailiwick of Jersey is similar to those
      found in recent studies of southern Britain. The standardised prevalence rates of
      probable and definite multiple sclerosis for the male populations were
      37.3/100,000 (95% CI 17.9-56.7) for the Bailiwick of Guernsey and 45.5/100,000
      (95% CI 26.3-64.7) for the Bailiwick of Jersey whereas the standardised
      prevalence rates for the female populations were 97.5/100,000 (95% CI 73.9-143.5)
      and 139.5/100,000 (95% CI 112.6-181.2) respectively. Thus there is a striking and
      unexplained 43% higher prevalence of probable and definite multiple sclerosis in
      the female population of Jersey compared with that of the Bailiwick of Guernsey.
      This seems to be due to an unusually low prevalence of the disease among the
      female population of the Bailiwick of Guernsey compared with that of the United
      Kingdom mainland.

PMID- 7823063
TI  - A prevalence survey of multiple sclerosis in Sussex.
AB  - A first survey of the Brighton and Mid-Downs health districts in Sussex showed a
      prevalence of multiple sclerosis of 111 per 100,000 (95% confidence interval (95%
      CI) 103-120) in a population of 596,594 on prevalence day, 1 July 1991. Cases
      were notified by multiple sources and to maximise case notification patients were
      not contacted. Cases were classified by hospital and family practitioner notes.
      The Poser criteria were used for classification. These criteria are precise and
      exclude cases of isolated spinal cord syndrome. The Allison and Millar criteria
      used in the surveys in Scotland may lack specificity and it is concluded that the
      high prevalence of multiple sclerosis in Scotland needs to be reassessed with the
      more precise criteria. Until this is done, the latitude effect within the United
      Kingdom remains not proved.

PMID- 7823064
TI  - Brain magnetic resonance imaging and multimodal evoked potentials in benign and
      secondary progressive multiple sclerosis.
AB  - Brain MRI and multimodal evoked potentials (EPs) were obtained for 13 patients
      with benign multiple sclerosis and 13 patients with secondary progressive
      multiple sclerosis, matched for age and duration of the disease, to investigate
      the nature of the disability in multiple sclerosis. Patients with secondary
      progressive multiple sclerosis had significantly greater lesion loads for five of
      seven periventricular regions and for three of nine regions separate from the
      ventricles. Patients with secondary progressive multiple sclerosis also had more
      severe infratentorial atrophy scores (p = 0.04), whereas there were no
      differences between the two groups in number and extent of enhancing lesions. The
      frequencies were significantly higher and severities greater for multimodal EP
      abnormalities of all the modalities in patients with secondary progressive
      multiple sclerosis. At least one EP component was absent in 12 (92%) patients
      with secondary progressive multiple sclerosis but in only one patient (8%) with
      benign multiple sclerosis (p < 0.001). There was neurophysiological evidence for
      cervical cord involvement in eight (61%) patients with secondary progressive
      multiple sclerosis and in one with benign multiple sclerosis (p < 0.01). These
      data indicate that the total amount of lesions, the distribution, and the nature
      of the pathological process might all account for the development of disability
      in multiple sclerosis.

PMID- 7823065
TI  - Neuropsychological impairments in chronic fatigue syndrome, multiple sclerosis,
      and depression.
AB  - To examine the degree and nature of cognitive impairments in chronic fatigue
      syndrome, a comprehensive neuropsychological battery was given to patients with
      chronic fatigue syndrome, multiple sclerosis, depressed patients, and healthy
      controls. The battery included tests of attention and concentration, information
      processing speed, verbal and visual memory, intellectual ability, and concept
      formation. Measures of depression and anxiety were also obtained. The chronic
      fatigue syndrome group did not differ from the depressed group in overall
      neuropsychological performance, but differed from the multiple sclerosis and
      control groups. The most significant impairment was in information processing
      speed in the chronic fatigue syndrome group. Depression and anxiety were not
      related to neuropsychological performance. The influence of reduced information
      processing on other areas of cognition is discussed.

PMID- 7823066
TI  - Phenobarbitone, phenytoin, carbamazepine, or sodium valproate for newly diagnosed
      adult epilepsy: a randomised comparative monotherapy trial.
AB  - Recent studies have shown that most newly diagnosed epileptic patients can be
      satisfactorily treated with a single antiepileptic drug. We therefore undertook a
      prospective randomised pragmatic trial of the comparative efficacy and toxicity
      of four major antiepileptic drugs, utilised as monotherapy in newly diagnosed
      epileptic patients. Between 1981 and 1987 243 adult patients aged 16 years or
      over, newly referred to two district general hospitals with a minimum of two
      previously untreated tonic-clonic or partial with or without secondary
      generalised seizures were randomly allocated to treatment with phenobarbitone,
      phenytoin, carbamazepine, or sodium valproate. The protocol was designed to
      conform with standard clinical practice. Efficacy was assessed by time to first
      seizure after the start of treatment and time to enter one year remission. The
      overall outcome with all of the four drugs was good with 27% remaining seizure
      free and 75% entering one year of remission by three years of follow up. No
      significant differences between the four drugs were found for either measure of
      efficacy at one, two, or three years of follow up. The overall incidence of
      unacceptable side effects, necessitating withdrawal of the randomised drug, was
      10%. For the individual drugs phenobarbitone (22%) was more likely to be
      withdrawn than phenytoin (3%), carbamazepine (11%), and sodium valproate (5%). In
      patients with newly diagnosed tonic-clonic or partial with or without secondary
      generalised seizures, the choice of drug will be more influenced by
      considerations of toxicity and costs.

PMID- 7823067
TI  - Which factors predict cognitive decline in Parkinson's disease?
AB  - The study assessed cognitive decline in non-demented, non-depressed patients with
      well defined Parkinson's disease and determined the predictive value for
      cognitive decline of different motor symptoms. Motor disability was measured with
      the Unified Parkinson's disease rating scale, impairment in activities of daily
      living, levodopa test, and long term clinical follow up. Neuropsychological
      evaluations included modified mini mental state, fluency, Wechsler logical
      memory, Wisconsin card sorting test, and the Montgomery and Asberg depression
      rating scale. Fifty three patients fulfilling clinical criteria for idiopathic
      Parkinson's disease were studied. Cognitive performance on initial testing was
      significantly correlated with education and disease duration but not with age at
      disease onset. Cognitive performance on retesting after three years of follow up
      was significantly reduced. This reduction was significantly greater in the late
      onset group, in patients with isolated dystonic dyskinesiae, and in patients with
      a lower percentage of motor improvement on levodopa. Cognitive decline in
      idiopathic Parkinson's disease may depend on both the prevalence of non
      dopaminergic lesions and the topography of dopaminergic denervation. Predictive
      factors for cognitive decline, especially in executive tasks, relate more to non
      dopaminergic than to dopaminergic lesions.

PMID- 7823068
TI  - Amyotrophic cervical myelopathy in adolescence.
AB  - The clinical and radiological features in seven patients who had asymmetric
      muscular atrophy of the hand and forearm when young are reported and a new
      hypothesis for its aetiology is proposed. Investigation of body growth curves (a
      surrogate for velocity of arm growth) showed close relation between (a) the age
      when the body height increased most rapidly and the onset age of this disorder,
      and (b) the age when the rapid body growth period ended and the age when symptom
      progression ceased. Cervical radiological evidence is provided showing asymmetric
      anterior cord atrophy, disappearance of slackness of dorsal roots in neck
      extension, and anterior and lateral displacement of the lower cervical cord
      against the posterior aspects of the vertebral bodies during neck flexion. These
      results suggest that disproportionate shortening of the dorsal roots is further
      accentuated during the juvenile growth spurt, which determines the onset and self
      limited course of the condition, and that repeated neck flexion causes micro
      trauma and relative ischaemia of anterior horn cells, which finally results in
      atrophy of the muscles innervated by motoneurons with long axons. Predisposing
      anatomical factors are a straight neck due to lack of physiological cervical
      lordosis and the presence of foreshortened dorsal roots.

PMID- 7823069
TI  - Mistletoe.

PMID- 7823070
TI  - Inherited Creutzfeldt-Jakob disease in a British family associated with a novel
      144 base pair insertion of the prion protein gene.
AB  - A case of familial Creutzfeldt-Jakob disease associated with a 144 base pair
      insertion in the open reading frame of the prion protein gene is described.
      Sequencing of the mutated allele showed an arrangement of six octapeptide
      repeats, distinct from that of a recently described British family with an
      insertion of similar size. Thirteen years previously the brother of the proband
      had died from "Huntington's disease", but re-examination of his neuropathology
      revealed spongiform encephalopathy and anti-prion protein immunocytochemistry
      gave a positive result. The independent evolution of at least two distinct
      pathological 144 base pair insertions in Britain is proposed. The importance of
      maintaining a high index of suspicion of inherited Creutzfeldt-Jakob disease in
      cases of familial neurodegenerative disease is stressed.

PMID- 7823072
TI  - Bilateral simultaneous optic neuropathy in adults: clinical, imaging,
      serological, and genetic studies.
AB  - To elucidate the cause(s) of acute or subacute bilateral simultaneous optic
      neuropathy (BSON) in adult life, a follow up study of 23 patients was performed
      with clinical assessment, brain MRI, HLA typing, and mitochondrial DNA analysis.
      The results of CSF electrophoresis were available from previous investigations in
      11 patients. At follow up, five (22%) had developed clinically definite multiple
      sclerosis, four (17%) had mitochondrial DNA point mutations indicating a
      diagnosis of Leber's hereditary optic neuropathy (LHON). The remaining 14
      patients (61%) still had clinically isolated BSON a mean of 50 months after the
      onset of visual symptoms: three of 14 (21%) had multiple MRI white matter lesions
      compatible with multiple sclerosis, three of 14 (21%) had the multiple sclerosis
      associated HLA-DR15/DQw6 haplotype, and one of seven tested had CSF oligoclonal
      IgG bands; in total only five (36%) had one or more of these risk factors. The
      low frequency of risk factors for the development of multiple sclerosis in these
      14 patients suggests that few will develop multiple sclerosis with more prolonged
      follow up. It is concluded that: (a) about 20% of cases of BSON without affected
      relatives are due to LHON; (b) multiple sclerosis develops after BSON in at least
      20% of cases, but the long term conversion rate is likely to be considerably less
      than the rate of over 70% seen after an episode of acute unilateral optic
      neuritis in adult life.

PMID- 7823071
TI  - Imaging the adult brain.

PMID- 7823073
TI  - Prognosis of deeply comatose patients on ventilators.
AB  - Although the concept of brain death has been widely accepted, the criteria
      required for making the diagnosis remain controversial. This prospective study
      was undertaken to examine the reliability of a set of clinical criteria adopted
      in Taiwan. One hundred and forty deeply comatose patients (101 men, 39 women;
      mean age 49.5 (SD 17.6) years) requiring ventilation were studied. Seventy three
      patients met the clinical criteria for brainstem death; all developed cardiac
      asystole (97% within seven days) despite continued full cardiorespiratory
      support. Brainstem death was diagnosed in only two of the 21 patients with
      hypoxic or ischaemic insults. This stresses the rarity of hypoxic or ischaemic
      encephalopathy as a cause of brainstem death. The results show that if strict
      attention is paid to preconditions and exclusions, brainstem death can be
      reliably diagnosed on clinical grounds alone.

PMID- 7823074
TI  - Verbal fluency in dementia of frontal lobe type and dementia of Alzheimer type.
AB  - This study compares semantic (category) and letter-initial verbal fluency
      performance in dementia of frontal lobe type, dementia of Alzheimer type, and
      control subjects matched for age, sex, and level of education. As well as
      demographic characteristics, patients were matched for severity of dementia as
      estimated by the mini mental scale (23.2 (SD 4.9)). All patients with dementia of
      frontal lobe type had a frontal hypoperfusion on single photon emission computed
      tomography whereas patients with dementia of Alzheimer type showed mainly
      posterior deficits. Patients had significantly lower verbal fluency than controls
      but those with dementia of frontal lobe type did not differ from those with
      dementia of Alzheimer type in the number of words generated, intrusions, or
      preservations. Category fluency was more impaired than letter fluency in both
      dementias. No correlation between frontal index, frontal/parietal index, and
      fluency was found. Verbal fluency tests are sensitive tools for detecting
      dementia but do not seem useful in distinguishing between patients with dementia
      of Alzheimer type and those with dementia of frontal lobe type in early disease.

PMID- 7823075
TI  - An improved diagnostic assay for Lambert-Eaton myasthenic syndrome.
AB  - A new immunoprecipitation assay has been established for detecting antibodies to
      voltage-gated calcium channels (VGCCs) in Lambert-Eaton myasthenic syndrome
      (LEMS), using 125I-omega-conotoxin MVIIC, which binds to P-type VGCCs, to label
      extracts of human cerebellum. Fifty six of 66 serum samples (85%) from patients
      with clinically and electrophysiologically definite LEMS were positive for the
      presence of VGCC antibodies, defined as a titre > 3 SD above the mean for the
      healthy controls (n = 10). All disease controls (n = 40) were negative. This
      sensitive immunoassay should prove valuable in the diagnosis of LEMS.

PMID- 7823076
TI  - Idiopathic orbital inflammation (orbital inflammatory pseudotumour): an unusual
      cause of transient ischaemic attack.
AB  - A patient with idiopathic inflammation of the right orbit, established by biopsy,
      developed episodes of transient left sensorimotor hemiparesis. Neuroimaging
      showed intracranial extension of the disease with pronounced narrowing of the
      right internal carotid artery in its intracavernous portion. Oral
      cyclophosphamide induced gradual improvement. Transient ischaemic attack is
      rarely found in association with orbital disease and indicates possible
      intracranial extension.

PMID- 7823077
TI  - Horizontal eye movement disorders after posterior vermis infarctions.
AB  - The horizontal saccade, smooth pursuit, and vestibulo-ocular reflex gains were
      recorded in 19 patients with cerebellar infarction documented with MRI, and in a
      group of control subjects. Bilateral saccade hypometria and a decrease in
      ipsilateral smooth pursuit gain were found only in patients with a lesion
      affecting the posterior vermis. These results in humans support experimental
      findings suggesting that the posterior vermis controls both saccade accuracy and
      smooth pursuit velocity.

PMID- 7823078
TI  - Somatosensory evoked blink response: findings in patients with Miller Fisher
      syndrome and in normal subjects.
AB  - Reflex blinking was elicited by the electrical stimulation of peripheral nerves
      and various parts of the body of seven of 11 patients with Miller Fisher
      syndrome. This reflex blinking disappeared during recovery. Reflex blinking was
      elicited in normal subjects only with specific stimulation of the peripheral
      nerves of their upper extremities. This response may be due to a release
      phenomenon transmitted via the brainstem reticular formation and may be useful in
      detecting latent CNS involvement in patients with Miller Fisher syndrome.

PMID- 7823079
TI  - Recruitment of a projection neuron determines gastric mill motor pattern
      selection in the stomatogastric nervous system of the crab, Cancer borealis.
AB  - 1. In the isolated stomatogastric nervous system of the crab Cancer borealis
      (Fig. 1), the muscarinic agonist oxotremorine elicits several distinct gastric
      mill motor patterns from neurons in the stomatogastric ganglion (STG; Fig. 2).
      Selection of a particular gastric mill rhythm is determined by activation of
      distinct projection neurons that influence gastric mill neurons within the STG.
      In this paper we identify one such neuron, called commissural projection neuron 2
      (CPN2), whose rhythmic activity is integral in producing one form of the gastric
      mill rhythm. 2. There is a CPN2 soma and neuropilar arborization in each
      commissural ganglion (CoG). The CPN2 axon projects through the superior
      esophageal nerve (son) and the stomatogastric nerve (stn) to influence neurons in
      the STG (Figs. 3 and 4A). 3. CPN2 activity influences most of the gastric mill
      neurons in the STG. Specifically, CPN2 excites gastric mill neurons GM and LG
      (gastric mill and lateral gastric, respectively) and inhibits the dorsal gastric
      (DG), anterior median (AM), medial gastric (MG), and inferior cardiac (IC)
      neurons (Figs. 5 and 6). CPN2 also indirectly inhibits gastric mill neurons Int1
      and VD (interneuron 1 and ventricular dilator neuron, respectively) through its
      activation of LG. The CPN2 excitatory effects are mediated at least partly via
      discrete excitatory postsynaptic potentials (EPSPs; Fig. 4B), whereas its
      inhibitory effects are produced via smooth hyperpolarizations. 4. Within the CoG,
      CPN2 receives excitatory synaptic input from the anterior gastric receptor neuron
      (AGR), a gastric mill proprioceptive sensory neuron (Fig. 7) and inhibitory
      synaptic input from the gastric mill interneuron, Int1 (Fig. 8). 5. During one
      form of the gastric mill rhythm, CPN2 fires rhythmically in time with the gastric
      mill motor pattern, whereas it is silent or fires weakly during other gastric
      mill rhythms (Fig. 9). 6. When CPN2 rhythmic activity is suppressed during a CPN2
      influenced gastric mill rhythm, the gastric mill rhythm continues, but the
      pattern is altered (Fig. 10). Moreover, transiently stimulating CPN2 during any
      ongoing gastric mill motor pattern can reset the timing of that rhythm (Fig. 11).
      7. Tonic activity in CPN2 is insufficient to elicit a gastric mill rhythm (Fig.
      12). Phasic activity in CPN2 can elicit a gastric mill rhythm only in
      preparations in which gastric mill neurons are already in an excited state (Figs.
      12 and 13). 8. CPN2 recruitment plays a pivotal role in determining the final
      form of the gastric mill rhythm.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7823080
TI  - Neurokinin 1 and 2 antagonists attenuate the responses and NK1 antagonists
      prevent the sensitization of primate spinothalamic tract neurons after
      intradermal capsaicin.
AB  - 1. Activation of neurokinin receptors contributes to the excitation of many
      dorsal horn neurons by cutaneous sensory stimuli, particularly noxious stimuli.
      In the present study we investigate the role of neurokinin receptors in the
      activation of primate spinothalamic tract (STT) neurons by cutaneous mechanical
      stimuli and by intradermal injection of capsaicin. This was done by testing the
      responses of these neurons to a battery of cutaneous stimuli before and during
      infusion by microdialysis of antagonists selective for NK1 and NK2 receptors. 2.
      The NK1 receptor antagonists cis-3-(2-methoxybenzyl-amino-2
      benzhydrylquinuclidine (CP96345) and D-Pro9-[Spiro-y-lactam]-Leu10,Trp11)
      Physalaemin(1-11) (GR82334) did not significantly reduce the responses of STT
      cells to mechanical stimulation of the skin. Both NK1 antagonists did, however,
      produce a significant reduction in the responses of STT neurons to an intradermal
      injection of capsaicin. Finally, despite having no effects on responses to
      mechanical stimuli, both NK1 antagonists prevented the sensitization of the
      responses to cutaneous stimuli that is usually observed after intradermal
      injections of capsaicin. 3. The NK2 selective antagonists PhCO-Ala-Ala-D-Trp-Phe
      D-Pro-Pro-Nle-NH2 (GR98400) and [Tyr5,D-Trp6,8,9,Lys10]-NKA (4-10) (MEN10376) had
      effects very similar to those of the NK1 antagonists, but with an important
      difference. Neither NK2 antagonist affected the responses of STT neurons to
      noxious or innocuous mechanical stimulation of the skin, but they did reduce the
      responses to intradermal capsaicin injections. These compounds failed to prevent
      capsaicin-induced sensitization. In fact, cells exposed to GR98400 or MEN10376
      showed unusually sustained increases in the responses to mechanical stimuli after
      the first capsaicin injection, suggesting that these compounds actually induced
      sensitization. 4. These results support the contention that both neurokinin
      receptors participate in the processing of nociceptive information in the dorsal
      horn, especially responses to strong stimuli such as intradermal injection of
      capsaicin. NK1 receptors are also involved in the sensitization of STT neurons
      after peripheral injury. A clearer understanding of the role of NK2 receptors in
      sensitization requires further studies with improved antagonists.

PMID- 7823081
TI  - Independent control of limb position and contact forces in cat posture.
AB  - 1. It has previously been demonstrated that a set of geometric and kinetic
      parameters are invariant in cats standing at their preferred interfoot distance
      and weight distribution. Thus the length and the angle of orientation relative to
      the vertical of each limb axis remain approximately constant when the supporting
      platform is tilted in the sagittal plane. The direction of the tangential contact
      forces is similarly constrained in response to horizontal translations. The main
      aim of the present study is to assess whether or not the control of limb position
      is independent of the control of the contact forces at the feet. To this end we
      have examined cat posture under a number of different conditions expressly
      designed to increase the range of postural variability. We considered that if the
      specification of limb position is a mere byproduct of the neural control of
      contact forces (or vice versa), geometric and kinetic parameters would covary
      interdependently. If instead limb position and contact forces are controlled in
      parallel and independently of each other, they will tend to follow different laws
      of variation. 2. Limb position and contact forces were measured in intact cats
      standing freely on a support platform. In a first series of experiments the pitch
      angle of the platform was randomly changed, as were the interfoot distance and
      head orientation. In another series of experiments cats were tilted in the
      presence of an external load tending to shift the weight distribution. The same
      load was applied in two different manners: 1) it made contact with a very limited
      surface of the body, and 2) it was attached by means of a long vest that made
      contact with most of the trunk and produced abnormal somesthesic cues to the
      body. 3. The range of different experimental conditions resulted in substantial
      trial-to-trial variations of the length and orientation of the axis of the limbs,
      as well as variations of the magnitude and orientation of the net contact forces.
      We found that the changes of the orientation of the contact force vector are
      uncorrelated with the corresponding changes of limb orientation, thus providing a
      first line of evidence in favor of the existence of a separate neural control of
      geometric and kinetic parameters. 4. Another line of evidence is provided by the
      specific form of the laws of variation of geometric parameters and tangential
      forces in different animals. Under normal (unloaded) conditions the values of the
      limb joint angles tend to covary linearly.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7823082
TI  - Coordinate transformations in the control of cat posture.
AB  - 1. Global geometric variables represent high-order parameters in the control of
      cat posture. In particular, limb length and orientation are accurately controlled
      in response to tilts of the support platform. There is now electrophysiological
      evidence, obtained in anesthetized cats, that spinal sensory neurons projecting
      to the cerebellum are broadly tuned to limb length and orientation. Limb length
      and orientation specify the position of the limb end-points in body-centered
      polar coordinates. They define an intended posture in a global manner, leaving
      the detailed geometric configuration of the limbs undetermined. The planar
      covariation of limb joint angles described in the accompanying paper suggests the
      existence of an intermediate processing stage that transforms endpoint
      coordinates into the angular coordinates of the joints (inverse mapping). In this
      paper we address the question of the nature of this coordinate transformation.
      Because the number of degrees of freedom of angular motion in each limb exceeds
      that of endpoint motion in world space, several different angular configurations
      are compatible with any given endpoint position in world space. Thus the problem
      of coordinate transformation is a priori indeterminate. We have tested a number
      of different hypotheses. 2. Coordinate transformation could be accomplished
      implicitly by means of discrete kinematic synergies. Any given geometric
      configuration of the limb would result from a weighed combination of only two
      distinct patterns of angular covariations, the first pattern affecting
      selectively limb length and the second pattern affecting limb orientation. This
      decomposition, however, was found in only a few sporadic cases. 3. We also tested
      the possibility that the coordinate transformation involves the Moore-Penrose
      generalized inverse. We found that this algorithm produces a planar covariation
      of the joint angles, but with an orientation orthogonal to the experimental
      plane. By contrast, a linear transformation with constant, position-independent
      terms can fit the experimental plane of angular covariations but predicts large
      errors in endpoint position. 4. The particular orientation in joint space of the
      experimental plane, coupled with the scatter of data points around the plane,
      bears a specific implication for the problem of inverse mapping. The experimental
      plane crosses the constant position lines (the loci of all possible changes of
      the joint angles that correspond with an invariant position of the endpoint) at
      an acute angle. Consequently the specification of limb orientation is little
      sensitive to joint configurations: relatively small changes in orientation can be
      produced by large changes in joint configurations.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7823083
TI  - Identification of molecular components of A-type channels activating at
      subthreshold potentials.
AB  - 1. Xenopus oocytes injected with rat brain mRNA express a transient K+ current
      similar to the A current that activates transiently near the threshold for Na+
      action potential generation (ISA) seen in somatic recordings from neurons. We
      used hybrid arrest with antisense oligonucleotides to investigate which of the
      cloned K+ channel proteins might be components of the channels responsible for
      the ISA expressed from brain mRNA. An oligonucleotide complementary to a sequence
      common to all known mammalian Shal-related mRNAs [KV4.1, KV4.2, and KV4.3 (the
      nomenclature of Sh K+ channel genes of Chandy and colleagues was used in this
      paper)] blocked the expression of the ISA. An oligonucleotide complementary only
      to the KV4.2 mRNA, the most abundant Shal-related transcript in rat brain RNA
      preparations, was also quite efficient in arresting the expression of the ISA
      from brain. These experiments indicate that Shal-related proteins are important
      components of the channels carrying the ISA expressed in oocytes injected with
      brain mRNA. However, there are several significant differences between this ISA
      and the currents expressed in the same oocytes by in vitro transcribed KV4.1 or
      KV4.2 cRNA. Most of these differences are eliminated if KV4.1 or KV4.2 cRNA is
      coinjected with brain poly-(A) RNA treated with antisense oligonucleotides which
      arrest the expression of the ISA, or with a 2-4Kb rat brain poly-(A) RNA fraction
      which does not express detectable K+ currents under the same recording
      conditions. These data support the hypothesis that ISA channels such as those
      expressed from brain mRNA contain Shal proteins that can be modified by proteins
      encoded in RNAs that by themselves do not express K+ currents.

PMID- 7823084
TI  - Blockade of NMDA-activated channels by magnesium in the immature rat hippocampus.
AB  - 1. N-methyl-D-aspartate (NMDA)-receptor single-channel currents were examined in
      outside-out patches from thin slices of rat hippocampus to examine possible age
      dependence in the Mg(2+)-block of NMDA-mediated responses. The kinetics of Mg2+
      block, among other channel properties, were compared between CA1 pyramidal cells
      from neonatal and 2-wk-old animals and dentate gyrus granule cells from neonatal
      and 4-wk-old animals. 2. Two distinct conductance states were seen consistently
      in nominally Mg(2+)-free solutions. The main conductance state was 50 and 56 pS
      in pyramidal cells and granule cells, respectively. The difference in NMDA
      receptor channel conductance between the two cell types was statistically
      significant at all ages examined. Both cell types exhibited a less frequent 35-
      to 40-pS conductance state. 3. Channel closing rates showed no intrinsic voltage
      dependence in Mg(2+)-free solutions in any group. Open times became strongly
      voltage dependent when Mg2+ was added. The rate of block by Mg2+ was similar in
      all groups. 4. Voltage and Mg2+ influenced primarily the shortest time constant
      of shut-time distributions. Longer components varied relatively little with
      voltage or [Mg2+]. The effects of voltage and [Mg2+] suggest that brief shuttings
      represent closed states in the absence of Mg2+ and primarily a Mg(2+)-blocked
      state in the presence of Mg2+. 5. The rate of unblocking by Mg2+ was similar in
      all groups. Thus the dissociation constant for Mg2+ binding (i.e., the ratio of
      the unblocking and blocking rates) also showed little variation. 6. NMDA-receptor
      channels in two regions of the hippocampus behaved in a qualitatively similar
      fashion both in neonates and 2-or 4-wk-old rats. These observations are
      inconsistent with previous studies obtained using other methods, which suggested
      that block of NMDA receptor channels by Mg2+ increases substantially with age.
      Nevertheless, subtle developmental and regional differences in other aspects of
      NMDA-receptor channel behavior were detected, perhaps reflecting variations in
      molecular structure tailored to specific functional requirements.

PMID- 7823085
TI  - Modulation of Ca(2+)-channel currents by protein kinase C in adult rat
      sympathetic neurons.
AB  - 1. Modulation of Ca(2+)-channel currents by phorbol-12-myristate-13-acetate (PMA)
      was investigated in acutely dissociated adult rat superior cervical ganglion
      neurons using the whole cell variant of the patch-clamp technique. 2. PMA (500
      nM) increased the current amplitudes, accelerated the inactivation of step
      currents, retarded the deactivation of tail currents, and shifted the tail
      current activation to more negative potentials. 3. The effects of PMA were
      concentration and voltage dependent and mediated through activation of protein
      kinase C (PKC). PMA also increased Ca2+ currents recorded with the perforated
      patch technique. 4. PMA affected the N-type Ca2+ channels and an omega-conotoxin
      GVIA-resistant current component. Ca2+ currents affected by PMA were not
      sensitive to omega-agatoxin IVA or nimodipine. 5. PMA not only attenuated Ca(2+)
      channel inhibition induced by alpha 2-adrenoceptor agonist, which modulates Ca2+
      channels via a pertussis toxin (PTX)-sensitive pathway, but also attenuated
      current inhibition by vasoactive intestinal polypeptide, which modulates Ca2+
      channels via a PTX-insensitive but cholera toxin-sensitive pathway. 6. PMA
      reversed Ca(2+)-channel inhibition induced by tonic activation of G-protein in
      the absence of neurotransmitter (even in neurons pretreated with PTX) or induced
      by activation of G-proteins with guanosine 5'-O-(3-thiotriphosphate) (GTP)-gamma
      S. 7. Inhibition of phosphatase by okadaic acid or substitution of Ba2+ for Ca2+
      in the external solutions accelerated the PMA effect. 8. Our results suggest that
      activation of PKC antagonizes G-protein mediated inhibition of Ca2+ channels by
      shifting Ca2+ channels from the "reluctant" state to the "willing" state. The G
      proteins and, more likely, the N-type Ca2+ channels may be the target of PKC
      phosphorylation. Protein phosphatases may be involved in counteracting the PKC
      phosphorylation in rat sympathetic neurons.

PMID- 7823086
TI  - Glutamate metabotropic receptors increase a Ca(2+)-activated nonspecific cationic
      current in CA1 hippocampal neurons.
AB  - 1. We studied the currents evoked in CA1 pyramidal neurons by the selective
      metabotropic glutamate receptor (mGluR) agonist 1S,3R-1-aminocyclopentane-1,3
      dicarboxylate (1S,3R-ACPD; 100 microM, 2.30-5 min) with the single-electrode
      voltage-clamp technique in the continuous presence of tetrodotoxin (1 microM),
      bicuculline (10 microM), 6-cyano-7-nitroquinoxaline-2,3-dione (15 microM), and D
      2-amino-5-phosphonovaleric acid (50 microM) to depress action potentials and
      synaptic activity. Microelectrodes were filled with 3M CsCl or 2 M Cs2SO4. 2.
      With CsCl-filled microelectrodes, bath application of 1S,3R-ACPD induced an
      inward current of -308 +/p 50 (SE) pA amplitude [holding potential (VH -60 mV, n
      = 12)] associated with a conductance decrease (26.5 +/- 5.6%, P < or = 0.0022, n
      = 12). The current-voltage (I-V) relation of the 1S,3R-ACPD-induced (difference)
      current investigated using ramp voltage commands from -130 to +10 mV had a V
      shape with two reversal potentials: -99.6 +/- 3.4 and -17.5 +/- 3.0 mV (n = 12).
      3. In contrast, in the presence of external K+ channel blockers (2 mM Ba2+ and 6
      mM Cs+ or 25 mM tetraethylammonium, 6 mM Cs+, and 3 mM 4-aminopyridine), 1S,3R
      ACPD also generated an inward current, albeit of smaller amplitude (-114.2 +/-
      27.5 pA, P < or = 0.003, VH -60 mV, n = 8). This current was associated with a
      conductance increase (20.7 +/- 3.1%, P < or = 0.0117, n = 8), decreased linearly
      with depolarization (from -130 to -60 mV), and reversed polarity at an estimated
      potential of -20.7 +/- 3.6 mV (n = 8). We refer to this current recorded in the
      presence of K+ channel blockers as IACPD. 4. In the presence of Cd2+ (200 microM,
      to block voltage-dependent Ca2+ channels that are readily activated in the
      presence of K+ channel blockers) and a low Ca2+ concentration (100 microM), IACPD
      decreased linearly from -130 to +10 mV and reversed polarity at -15.8 +/- 8.5 mV
      (n = 5).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7823087
TI  - Characteristics of somatotopic organization and spontaneous neuronal activity in
      the region of the thalamic principal sensory nucleus in patients with spinal cord
      transection.
AB  - 1. We explored the region of the principal sensory nucleus of thalamus (Vc)
      during stereotactic surgical procedures for treatment of patients with pain after
      spinal cord transection (n = 23). Receptive fields (RFs) of thalamic single
      neurons and locations of sensations evoked by stimulation (projected field, PF)
      were determined by standard methods. The cellular thalamic region where
      sensations were evoked at < 25 microA was termed the "region of Vc." The region
      of Vc in spinal patients was subdivided into different areas according to RF and
      PF locations. Areas that were distant from the representation of the anesthetic
      part of the body were termed "spinal control" areas, whereas those that were
      adjacent to or included in the representation of the area of absolute sensory
      loss were termed "border zone/anesthetic" areas. The region of Vc in movement
      disorder patients were termed the "control" area. 2. Border zone/anesthetic areas
      of thalamus often exhibited increased representations of the border of the
      anesthetic part of the body in comparison with the representation of the same
      parts of the body in control and spinal control areas. 3. In control and spinal
      control areas the locations of RFs and PFs were usually well matched. However, in
      border zone/anesthetic areas of the thalamus there was frequently a mismatch
      between the location of RFs and PFs (RF/PF mismatch). In border zone/anesthetic
      areas, RFs were often located on the border of the anesthetic part of the body
      whereas PFs were referred to anesthetic parts of the body. 4. Analysis of first-
      and higher-order properties of spontaneous neuronal activity revealed that spike
      trains could be classified into two groups with distinct patterns of activity.
      The R group (n = 49) was characterized by independence of sequential interspike
      intervals (ISIs), a Poisson distribution of ISIs, initially inhibitory or flat
      autocovariance function (acvf), and low level of high-frequency bursting. The O
      group (n = 26) was characterized by correlation of sequential ISIs, large
      sustained postspike facilitation on the acvf, and high prevalence of high
      frequency bursting--all consistent with a bursting pattern of activity. A third
      group of spike trains (n = 17) had an initially inhibitory or flat acvf and a
      unimodal, positively shifted, ISI distribution that did not meet criteria for a
      Poisson distribution. 5. Spike trains in the R group were much more common in
      control and control spinal areas, whereas those in the O group were more common
      in border zone/anesthetic areas.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7823089
TI  - The learning of novel finger movement sequences.
AB  - 1. Experienced typists typed phrases containing words in which one isolated
      letter was typed with one hand, while the remaining letters were typed with the
      contralateral hand. 2. The translational and rotational motion of the fingers and
      wrist of the right hand were obtained optoelectronically from the location of
      reflective markers placed on the fingers. 3. Midway through the experiment, the
      key corresponding to the isolated letter was physically switched with another key
      on the keyboard, and subjects typed the letter in its new location (for 140
      trials). The letter "n," typed with the right index finger, was either switched
      with letters normally typed with the same finger (u), with a different finger but
      same hand (o), with the same finger of the left hand (v), or with a different
      finger of the left hand (w). 4. When the words were typed normally, the interkey
      intervals were relatively short, and the onset of movement of the right hand
      began before the preceding keypress with the left hand. Thus the movement of the
      two hands overlapped. Furthermore, the movement to the isolated key was highly
      stereotypical, with little trial-to-trial variability. 5. After the transposition
      of keys, there were prolongations in the interkey intervals, with the largest
      delay occurring directly before the typing of the transposed key. Switches
      between homologous fingers (involving mirror movements) delayed the onset of
      keypresses to a lesser extent than did other switches. With practice, these
      delays were reduced but never reached the control level. 6. After the keyswitch,
      the onset of movement to the isolated key did not occur on average until after
      the last keypress with the contralateral hand, except when the switch involved
      the use of homologous fingers. In the latter case, overlapping movement of the
      two hands was maintained. Thus the learning of a series of discrete movements
      does not necessarily require that each movement segment be performed
      sequentially. 7. After the transposition of keys, the movement pattern and time
      course to a given key were similar to the movement patterns for that key observed
      during control trials in all conditions. Thus the learning of a series of
      movements may involve the use of previously learned movements under new
      conditions. 8. The results suggest that typing movements may be organized at
      several levels, including the individual keystroke and word level.

PMID- 7823088
TI  - The synaptic activation of N-methyl-D-aspartate receptors in the rat medial
      vestibular nucleus.
AB  - 1. We examined the synaptic activation of N-methyl-D-aspartate (NMDA) receptors
      by stimulation of primary vestibular afferent projections to second-order neurons
      in the medial vestibular nucleus (MVN) using whole cell patch-clamp recording
      methods in rat brain stem slices maintained in vitro. 2. Stimulation of the
      vestibular nerve (nVIII) evoked monosynaptic excitatory postsynaptic potentials
      (EPSPs) in second-order MVN neurons. Bath application of the gamma-aminobutyric
      acid receptor antagonist bicuculline (10 microM) revealed a late, slow EPSP that
      was blocked by the NMDA receptor antagonist D-2-amino-5-phosphonovalerate (D-AP5;
      50 microM) and displayed a voltage-dependent reduction at hyperpolarized
      potentials in the presence of external magnesium (1 mM). The early component of
      the nVIII-evoked EPSP in the presence of bicuculline was blocked by the alpha
      amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist 6,7
      dinitroquinoxaline-2,3-dione (DNQX; 10 microM) and displayed linear current
      voltage relations in the presence of external magnesium. 3. In some cells both
      components of the EPSP were blocked by DNQX, whereas only the late component was
      sensitive to D-AP5, indicating that NMDA receptors also mediate excitation via
      intrinsic pathways within MVN. 4. The NMDA receptor-mediated excitatory
      postsynaptic current (EPSC) evoked by nVIII stimulation was recorded in voltage
      clamped MVN neurons in a magnesium-free saline containing bicuculline (10 microM)
      and DNQX (10 microM). At -80 mV the NMDA receptor-mediated EPSC (latency = 2.7
      ms) displayed a slow rise time (10-90%, 5.8 ms) and exhibited a biexponential
      decay [time constant of fast component of decay (tau s) = 27.6 ms, time constant
      of slow component of decay (tau s) = 147.4 ms].(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7823090
TI  - Adenosine inhibition of synaptic transmission in the substantia gelatinosa.
AB  - 1. We studied adenosine's action on synaptic transmission from primary afferent
      fibers to neurons of the substantia gelatinosa (SG) using tight-seal whole cell
      recordings in transverse slices of hamster spinal cord. Adenosine had two
      actions, hyperpolarization of the postsynaptic membrane and depression of the
      excitatory postsynaptic currents (EPSCs) evoked by dorsal root stimulation. 2.
      Under voltage clamp adenosine elicited a sustained outward current at a holding
      potential of -70 mV. The outward current was blocked by a combination of
      intracellular cesium and tetraethylammonium, an effect characteristic of
      potassium channels. The adenosine-induced current reversed at -97 +/- 6 (SD) mV,
      close to the potassium equilibrium potential. These observations suggest that
      adenosine activates a potassium conductance in SG neurons so as to inhibit
      primary afferent synaptic transmission postsynaptically. 3. Adenosine reduced the
      miniature EPSC frequency without significantly changing the amplitude. In
      contrast, the glutamate receptor competitive antagonist 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX) substantially reduced the amplitudes of
      miniature EPSCs while producing a much smaller effect on the miniature frequency
      than adenosine. In evoked EPSCs adenosine reduced unitary content without
      reducing unitary amplitude. The effects on both miniature and evoked EPSCs
      suggest that adenosine inhibits synaptic currents by suppressing presynaptic
      transmitter release. 4. EPSCs evoked by dorsal root stimuli were subdivided into
      monosynaptic and polysynaptic categories. Adenosine at superfusion concentrations
      of 20-300 microM suppressed all polysynaptic EPSCs. Less than half of
      monosynaptic EPSCs were inhibited, usually those evoked by the slowest-conducting
      primary afferents. These observations were interpreted to indicate that a
      principal action of adenosine in SG is on interneuronal communication.

PMID- 7823091
TI  - Nicotinic and muscarinic activation of motoneurons in the crayfish locomotor
      network.
AB  - 1. We investigated the effects of acetylcholine (Ach) on identified motoneurons
      (MNs) using an in vitro preparation of the crayfish thoracic nervous system.
      Discontinuous current-clamp and single electrode voltage-clamp recordings from 50
      MNs were performed along with micropipette pressure ejection of Ach (or agonists)
      close to the recording electrode. 2. Localized ejections of relatively large
      volumes (500-2,500 pl) of Ach (10(-2) M) or of the muscarinic agonist
      oxotremorine (Oxo, 10(-2)M) onto the MN neuropile region, usually (90% of the
      cases) induced a slow, alternating rhythmic activity in antagonistic MNs. In
      other cases (4 experiments), with similar deliveries of Ach or Oxo, MNs developed
      the ability to fire rhythmically but only when depolarized by sustained current
      injection. Pressure ejections of smaller volumes (50-200 pl) of Ach (10(-2)M)
      close to the recorded MN could give rise to a fast (1-2 s) large amplitude (< or
      = 20 mV) membrane depolarization (12%), a long-lasting (10 s to several minutes)
      and small (2-5 mV) depolarization (14%), and a combination of the two (74%).
      These responses appeared to involve different regions of the neurite because they
      changed when the drug-ejection pipette was displaced in the neuropile. Moreover,
      fast and long-lasting depolarizing components resulted from a direct effect of
      Ach onto the MNs because they persisted under tetrodotoxin (TTX, 10(-6)M) and
      cobalt (Co2+, 5 x 10(-3) M) superfusion. 3. Whereas the membrane resistance
      decreased during the fast Ach-induced depolarization, it increased during the
      long-lasting depolarization. The increase in membrane resistance was more
      pronounced at depolarized potentials more than -55 mV and involve a reduction in
      K+ conductance. 4. Superfusion with nicotinic and muscarinic antagonists revealed
      that the fast Ach-induced depolarization involved nicotinic receptors, muscarinic
      receptors, or both, whereas the slow depolarization was exclusively muscarinic.
      5. The Ach-evoked inward currents were studied under voltage clamp. The fast
      nicotinic component (Inic) increased with hyperpolarizing holding potentials and
      decreased with depolarizing potentials, reversing at between 10 and 30 mV. The
      fast muscarinic current (Ifmus) displayed similar characteristics and reversed at
      about -10 mV. Whereas both fast components were voltage independent, the long
      lasting muscarinic component (Ismus) was voltage dependent. The response grew
      with membrane depolarization, but when the holding potential was hyperpolarized
      below resting level, the response declined to disappear at about -60 mV and
      beyond.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7823092
TI  - Neural responses related to smooth-pursuit eye movements and their correspondence
      with electrically elicited smooth eye movements in the primate frontal eye field.
AB  - 1. Intracortical microstimulation of a portion of the monkey frontal eye field
      (FEF) lying in the floor and posterior bank of the arcuate sulcus evokes smooth,
      rather than saccadic eye movements. To further explore this region's involvement
      in pursuit, we recorded from FEF neurons in the vicinity of sites from which
      smooth eye movements (SEMs) were elicited electrically and studied their
      responses during smooth-pursuit and saccadic tasks. In this report, we describe
      the neurons' responses during visually guided smooth pursuit and compare their
      locations and response properties with those of elicited SEMs. 2. One hundred and
      ninety-three neurons, recorded from the FEF region in six hemispheres of three
      rhesus monkeys, were classified as "pursuit neurons". These neurons responded
      during smooth-pursuit tracking of moving visual stimuli but had no, or only
      minimal, responses in conjunction with visually guided saccades. Pursuit neurons
      were located in a small region of the arcuate fundus and posterior bank that
      overlapped, and extended slightly beyond, the region from which SEMs were
      elicited with microstimulation. 3. All pursuit neurons had a preferred pursuit
      direction, and all directions were represented with no strong bias toward
      ipsilateral, contralateral, up, or down. The directional tuning of 80 pursuit
      cells was measured quantitatively by testing pursuit in several directions and
      fitting the responses to a Gaussian function. Tuning indices (the sigma parameter
      of the Gaussian fit) varied between 13 degrees and 136 degrees. The median tuning
      index, 44.5 degrees, corresponds to a full width at half maximum of 105 degrees.
      The ubiquity of selectivity for pursuit direction and the wide distribution of
      preferred directions indicates that pursuit direction uses a place-code type of
      representation in FEF; however, the broad directional tuning of most neurons
      suggests that pursuit direction is given by a weighted average of optimal
      directions across the population of pursuit neurons active at any given time. 4.
      In general, the responses of pursuit neurons increased with pursuit velocity. Of
      13 neurons formally tested with 2 s of constant-velocity tracking in their
      preferred direction across a range of target speeds, pursuit velocity sensitivity
      ranged from 0.24 to 1.42 spikes.s-1.deg-1.s-1, with an average sensitivity of
      0.70. This relationship suggests that pursuit neurons represent pursuit magnitude
      using a rate code; this parallels our previous observation that at most SEM
      sites, the velocity and acceleration of the electrically elicited eye movements
      increased as a function of the stimulation current.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7823093
TI  - Vibration-entrained and premovement activity in monkey primary somatosensory
      cortex.
AB  - 1. Primary somatosensory cortical (SI) neurons exhibit characteristic activity
      before the initiation of movements. This premovement activity (PMA) may result
      from centrally generated as well as from peripheral inputs. We examined PMA for
      55 SI neurons (10, 13, 28, and 4 in areas 3a, 3b, 1, and 2, respectively) with
      activity that was entrained to vibrotactile stimulation (i.e., was temporally
      correlated with the stimulus). We sought to determine whether the temporal
      characteristics of vibration-entrained discharges would change throughout the
      reaction time period, and, if they did, whether these changes might be accounted
      for by central inputs. 2. Monkeys made wrist flexions and extensions in response
      to sinusoidal vibration (27, 57, or 127 Hz) of their palms. Vibration remained on
      until the animal moved at least 5 degrees from the initial hold position. Mean
      firing rate (MFR), a measure of the level of activity, was derived from the
      number of spikes per vibratory cycle. The correlation between the vibration and
      the neuronal firing was described by the mean phase (MP) of the vibratory cycle
      at which spikes occurred. The degree of entrainment was quantified as
      synchronicity (Synch), a statistical parameter that could change from 0 for no
      entrainment to 1 for responses at a constant phase. 3. Premovement MFR increases
      (activation) and decreases (suppression) were observed. Moreover, two changes in
      MFR often were observed for the same neuron (2-event PMA). Many MFR shifts,
      especially the first in the two-event PMA, preceded electromyographic (EMG)
      onset. The pre-EMG MFR shifts more often had the same sign both for flexion and
      extension movements rather than having opposite signs. However, with equal
      frequency, post-EMG PMA events had the same or opposite sign for different
      movement directions. We suggest that the pre-EMG PMA has an origin different from
      movement-related peripheral reafference. 4. Premovement activation was
      accompanied by shifts of MP corresponding to earlier responses to the ongoing
      vibratory stimulus and by decreases of response Synch. Premovement suppression
      was not associated with consistent shifts of MP and Synch. We suggest that during
      premovement activation, asynchronous (uncorrelated with vibration) signals are
      integrated with the vibratory input. These asynchronous signals may make neurons
      more likely to discharge and to do so earlier with respect to the vibratory
      stimulus. The asynchronous component may also disrupt the vibration-entrained
      activity pattern.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7823094
TI  - Interactions between the eye and hand motor systems: disruptions due to
      cerebellar dysfunction.
AB  - 1. We tested the hypothesis that interactions occur between eye and hand
      movements produced in conjunction. This was accomplished by having human subjects
      with cerebellar dysfunction and age-matched controls perform two tasks: 1)
      tracking a moving target with the hand and 2) performing a pointing movement to
      intercept the target. Our prediction was that the inaccuracies that are
      characteristic of eye and hand movements generated in isolation by cerebellar
      subjects would be accentuated in each system during combined eye-hand tasks. 2.
      The cerebellar subjects took longer to respond to the onset of target motion in
      both tasks. This was true for both the eyes and hand, regardless of whether the
      eye and hand movements were generated in isolation or in conjunction with each
      other. 3. The cerebellar subjects also displayed a larger degree of error and/or
      variability in their hand movements than the control subjects. A significant
      amount of this increased variability was due to systematic changes in the
      trajectory of the hand during the critical periods leading up to and after each
      ocular saccade. These systematic changes were consistent with an overestimation
      of target velocity in the perifoveal visual field. 4. The increased variability
      of the cerebellar subjects' hand movements was markedly reduced by restricting
      eye movements. A similar reduction in variability occurred when vision of the
      hand was restricted in the tracking task. This effect was accompanied by improved
      eye movements. 5. For both sets of subjects the eye movements were affected by
      the hand movements produced in the tracking task. In particular, eye movement
      accuracy was improved in the controls and degraded in the cerebellar subjects
      when compared with the eye movements generated in isolation. In contrast, no
      changes were observed in the interception task. 6. Taken together, these results
      imply that a reciprocal interaction occurs between the eye and hand motor systems
      and/or that common "upstream" sites influence each of these systems in a similar
      manner. The functional anatomy and neurophysiological characteristics of several
      sites where such interactions may take place are discussed.

PMID- 7823095
TI  - Inhibition of glutamate release by presynaptic kappa 1-opioid receptors in the
      guinea pig dentate gyrus.
AB  - 1. Activation of kappa 1-opioid receptors inhibits excitatory transmission in the
      hippocampal dentate gyrus of the guinea pig. The present studies used both
      anatomic and physiological approaches to distinguish between a pre- and
      postsynaptic localization of these receptors. 2. The entorhinal cortex was
      lesioned unilaterally to cause degeneration of perforant path afferents to the
      dentate molecular layer, and kappa 1-opioid binding sites were measured by
      labeling with the selective agonist, [3H]-U69593. Binding density was reduced
      significantly in the dentate gyrus molecular layer ipsilateral to the lesion
      compared with the contralateral molecular layer and with sham-lesioned controls.
      3. Paired-pulse facilitation is a neurophysiologic paradigm that has been used to
      differentiate pre- and postsynaptic sites of action for agents that inhibit
      excitatory neurotransmission. U69593 reduced the amplitude of single population
      spikes and increased the degree of paired pulse facilitation. The potentiation of
      paired-pulse facilitation was maintained when the stimulation intensity was
      increased to compensate for the inhibition of excitatory transmission. These
      effects of kappa 1-receptor activation were similar to those seen after
      presynaptic inhibition of excitatory neurotransmitter release and support the
      hypothesis that U69593 presynaptically inhibits excitatory amino acid release in
      the dentate gyrus. 4. Local application of glutamate by pressure ejection in the
      dentate molecular layer evoked field excitatory postsynaptic potentials that
      mimicked those evoked by electrical stimulation of the perforant path. Both
      responses were sensitive to the non-N-methyl-D-aspartate glutamate receptor
      antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione. U69593 inhibited responses
      evoked by perforant path stimulation but had no effect on responses evoked by
      glutamate application.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7823096
TI  - Developmental regulation of plasticity in cat somatosensory cortex.
AB  - 1. The neocortical response to deprivation of somatic sensory input in young
      animals of different ages was compared with the same manipulation in adults. The
      response was measured through the use of 2-deoxyglucose (2DG) mapping. Although
      several features of the cortical response were similar in animals of all ages,
      the metabolic patterns evoked by somatic stimulation differed substantially from
      each other at all ages. 2. When adult cats receive a digit amputation and survive
      from 2 to 8 wk, the pattern of stimulus-evoked metabolic uptake expands
      dramatically in the somatosensory cortex contralateral to the deprived forepaw.
      Comparisons between the normal and experimental somatosensory cortices reveal
      that the distribution of activity on the experimental side was roughly an
      expanded version of the normal pattern. 3. Unilateral digit amputations of digit
      2 were conducted on kittens 2, 4, or 6 wk old. They survived until 3-4 mo and
      then received a 2DG experiment, during which digit 3 was stimulated bilaterally.
      Evaluation of the evoked metabolic pattern indicated substantial differences from
      the activity elicited in adults undergoing identical manipulations. 4. The
      individual patches of activity that made up the metabolic pattern were similar in
      intensity in both hemispheres when the digit amputation was conducted at either
      2, 4, or 6 wk. After a digit amputation at 2 wk, the patches were significantly
      narrower in the experimental hemisphere; after a digit amputation at 6 wk, the
      patches were significantly wider in the hemisphere receiving from the deprived
      forepaw. 5. Two-dimensional maps of 2DG uptake in areas 3b and 1 of the
      somatosensory cortex reveal that after a digit amputation at 2, 4, or 6 wk, the
      distribution of activity in the hemisphere receiving from the digit amputation
      was more dispersed and widespread than in the normal hemisphere. The dispersed
      pattern of uptake was not an expanded version of the normal pattern, but
      scattered over a wider region of somatosensory cortex. This observation is
      similar to the normal pattern of evoked activity seen in developing animals. 6.
      The total area of 2DG uptake in the somatosensory cortex contralateral to a digit
      amputation conducted at 2 or 4 wk was not greater than that in the normal
      hemisphere, even though it was more widespread. After a digit amputation at 6 wk,
      however, the area of evoked activity was greater in the experimental hemisphere
      but not of the magnitude as the same manipulation in an adult.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 7823097
TI  - Network interactions among limbic cortices, basal forebrain, and cerebellum
      differentiate a tone conditioned as a Pavlovian excitor or inhibitor:
      fluorodeoxyglucose mapping and covariance structural modeling.
AB  - 1. The objective was to examine how opposite learned behavioral responses to the
      same physical tone were differentiated by the pattern of interactions between
      extraauditory neural regions. This was pursued using a new approach combining
      behavior, neuroimaging, and network analysis to integrate information about
      differences in regional activity with differences in the covariance relationships
      between brain areas. 2. A tone was used as either a Pavlovian conditioned excitor
      or inhibitor. Rats were conditioned with reinforced trials of a conditioned
      excitor (A+) intermixed with nonreinforced trials of a tone-light compound (AX-).
      The tone was the excitor (A+) for the tone-excitor group and was the inhibitor (X
      ) for the tone-inhibitor group. After conditioning, all rats were injected with
      [14C(U)]2-fluoro-2-deoxyglucose (FDG) and presented with the same tone. 3. FDG
      autoradiography was used to measure regional activity and to generate
      interregional correlations of activity resulting from the presentation of the
      tone. A stepwise discriminant analysis was used to select brain regions that
      differentiated the excitor from the inhibitor effects. 4. Network analysis
      consisted of constructing an anatomic model of the brain regions, selected by the
      discriminant analysis, linking the regions with their known anatomical
      connections. Then, functional models for the tone-excitor and -inhibitor groups
      were constructed using structural equation modeling. Correlations of activity
      between regions were decomposed to calculate numerical weights, or path
      coefficients, for each anatomic path. These path coefficients were used to
      compare the interactions for the tone-excitor and -inhibitor models. 5. Regional
      differences in FDG uptake were found in the sulcal frontal cortex (SFC), lateral
      septum (LS), medial septum/diagonal band (MS/DB), retrosplenial cortex (RS), and
      dentate-interpositus nuclei of the cerebellum (DEN). Discriminant analysis
      selected three other regions that significantly discriminated the tone-excitor
      and -inhibitor groups: perirhinal cortex (PRh), nucleus accumbens (ACB), and the
      anteroventral nucleus of the thalamus (AVN). 6. Structural equation modeling
      identified two functional circuits that differentiated the groups. One involved
      the basal forebrain regions (LS, MS/DB, ACB) and the other limbic thalamocortical
      structures (SFC, RS, PRh, AVN). Differences in the interactions within these
      circuits were mainly in sign of the covariance relationships between regions,
      from positive for the tone-excitor model to negative path coefficients for the
      tone-inhibitor model. The path coefficient between the basal forebrain circuit
      and the limbic thalamocortical circuit showed the largest magnitude difference.
      This quantitative difference was mediated by a path from the MS/DB to
      PRh.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7823098
TI  - Encoding of amplitude and rate of forces applied to the teeth by human
      periodontal mechanoreceptive afferents.
AB  - 1. The encoding of force amplitude and force rate by human periodontal
      mechanoreceptive afferents was studied. Recordings were obtained from 19 single
      periodontal afferents in the inferior alveolar nerve with the use of tungsten
      microelectrodes. Loads consisting of a force increase (loading ramp), a phase of
      maintained force (static phase), and a force decrease (unloading ramp) were
      applied to the receptor bearing tooth, which was most often an incisor. The
      static forces applied ranged between 0.05 and 5 N, and the rate of force applied
      during the loading ramps ranged between 0.4 and 70 N/s. The forces were primarily
      applied in one of six directions (lingual, labial, mesial, distal, upward, or
      downward) that evoked the greatest discharge activity. 2. For each force
      application, the steady-state response was defined as the mean discharge rate
      during a 1-s period starting 0.5 s after the end of the loading ramp. Most
      afferents (15/19) exhibited a "hyperbolic" (viz., negatively accelerating)
      relationship between the amplitude of the stimulation force and the steady-state
      response, featuring a pronounced saturation tendency: the highest sensitivity to
      changes in static force was observed at force levels below 1 N. At higher force
      levels the sensitivity gradually diminished. Moreover, the dynamic sensitivity
      similarly decreased with increasing amplitude of static background force. For a
      subsample of afferents studied, comparable stimulus-response relationships were
      obtained in directions other than the most responsive one, but the discharge
      rates were lower. 3. In contrast to the response of most afferents, four (4/19)
      differed in that they consistently exhibited a nearly linear relationship between
      force amplitude and the steady-state response. Moreover, these afferents
      maintained their dynamic sensitivity as the amplitude of the background force was
      increased. 4. The steady-state response of all afferents was well described as a
      constant times F/ (F + c), where F represents the steady-state force, and c the
      force generating one-half the estimated maximum discharge rate that could be
      evoked by steady-state force stimulation. The c-parameter was on average 0.42 N
      (range 0.05-1.1 N) for the afferents exhibiting hyperbolic stimulus-response
      relationships. In contrast it ranged between 5 and 22 N for those exhibiting
      "nearly linear" relationships. A hypothetical model of the mechanics of the
      periodontal ligament supporting the F/(F + c) transform is proposed. 5. A general
      transfer function was developed to predict the instantaneous discharge rate of an
      individual afferent to arbitrary force profiles applied to the receptor bearing
      tooth.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7823099
TI  - Short-term homeostasis of active sleep and the architecture of sleep in the rat.
AB  - 1. Sixteen rats were recorded continuously for 3 days using an automated system
      that detected, quantified, and stored the incidence of cortical delta waves,
      cortical sigma spindles, hippocampal theta rhythm, and electromyographic
      activity. A time series then was constructed wherein 15-s epochs were ascribed to
      one behavioral state: wakefulness (W), quiet sleep (QS), or active sleep (AS, a
      state also referred to as REM sleep). From those series, AS episodes and non-AS
      intervals could be determined. Episodes and intervals were defined as lasting at
      least two epochs and the one-epoch episodes and intervals were incorporated to
      the ongoing state. 2. Having established the length of each AS episode and non-AS
      interval, pairings were made, on the one hand between episodes and their
      preceding intervals, and on the other, between episodes and the intervals that
      followed. 3. Highly significant correlations were found between the length of AS
      episodes and the length of the non-AS intervals that followed. Correlations were
      also significant when calculated separately versus the amount of QS and of W
      within the following interval. Correlations improved when they were performed
      against the log of the interval and when only intervals with a predominance of QS
      were selected. 4. No significant correlation was found between the length of AS
      episodes and the length of the preceding non-AS intervals, except for a negative
      one that was present only when the statistical analysis was performed in the
      unsmoothed array where the one-epoch episodes and intervals were preserved. 5.
      These results suggest that there is a short-term homeostasis operating within the
      spontaneous architecture of sleep in rats. This homeostatic mechanism is not
      manifested by the regulation of the length of AS episodes. Instead, there is a
      forward regulatory mechanism that, given the duration of an AS episode,
      permissively controls the interval that the animal may abstain from AS, and hence
      the timing of the triggering of a new AS episode.

PMID- 7823100
TI  - Spread of epileptiform activity in the immature rat neocortex studied with
      voltage-sensitive dyes and laser scanning microscopy.
AB  - 1. Adult rats and rats with a postnatal age of 3-29 days (PN 3-29) were used for
      the preparation of in vitro slices of the frontal neocortex. Epileptiform
      activity was induced by bath application of the gamma-aminobutyric acid-A (GABAA)
      receptor antagonists bicuculline or picrotoxin. 2. The voltage-sensitive dye RH
      414 and a laser scanning microscope were used for multiple-site optical
      recordings of membrane potential changes associated with epileptiform activity.
      Optical signals were compared with simultaneously measured extra-cellular field
      potentials. 3. Optical signals could be reliably recorded for the duration of the
      experiments (2-4 h). Extracellular recordings of convulsant-induced paroxysmal
      depolarizing shifts (PDSs) in slices stained with RH 414 were comparable with
      those obtained in unstained slices. Changes in dye signals in response to
      reductions in extracellular calcium, addition of tetrodotoxin (TTX), or
      application of excitatory amino acid receptor antagonists indicate that the
      fluorescence changes correlate well with established electrophysiological
      measures of epileptiform activity. 4. In slices from adult animals, dye signals
      were observed at all recording sites. The response with the shortest latency
      occurred invariably at the site of stimulation, and activity spread rapidly in
      both vertical and horizontal directions. Spread was significantly faster in the
      vertical than in the horizontal direction. 5. Epileptiform activity was absent or
      only weakly expressed in slices from PN 3-9 animals. Activity was detectable
      predominantly in upper cortical layers. 6. Dye signals were observed at all
      measurement points in slices from PN 10-19 animals. In this age group, peak
      amplitude increased with spread of activity from lower to upper cortical layers.
      There was no significant difference between the speed of propagation in the
      vertical and in the horizontal directions. Spontaneous epileptiform activity
      occurred at a high rate in the PN 10-19 age group, and signals associated with
      spontaneous epileptiform events were largest in upper layers. 7. In the PN 10-19
      age group, optical signals were characterized by the repetitive occurrence of PDS
      discharges superimposed on a sustained response. The amplitude of the sustained
      response decreased with increasing distance from the site of stimulation.
      Analysis of the latencies revealed that the superimposed PDS-like events were
      generated at multiple sites within the scanning area. Amplitude and rate of rise
      were largest in slices from PN 10-19 animals. These values declined with ongoing
      development.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7823101
TI  - Homosynaptic facilitation of transmitter release in crayfish is not affected by
      mobile calcium chelators: implications for the residual ionized calcium
      hypothesis from electrophysiological and computational analyses.
AB  - 1. Evoked neurotransmitter release at the crayfish neuromuscular junction was
      measured in the presence of the cell-permeant calcium chelator 1,2-bis(2
      aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetotoxymethyl (BAPTA-AM).
      Excitatory post-synaptic potentials were greatly diminished after application of
      the intracellular chelator, an effect resulting from attenuation of the rise in
      the concentration of cytoplasmic Ca2+ ([Ca]i) that is necessary for
      neurotransmission. However, short-term homosynaptic facilitation of release, the
      magnitude and time course of which is thought to depend on the accumulation and
      removal of residual Ca ions (Ca2+), was not affected. Application of the cell
      permeant form of ethylene glycol-bis-(beta-aminoethyl ether)-N,N,N',N'
      tetraacetic acid (EGTA) gave similar results. 2. To interpret these results we
      developed a reaction-diffusion model in 3D rectangular coordinates for Ca2+
      diffusion in the presence of mobile and immobile buffers. Solutions of the model
      in response to influx of Ca2+ through one or six channels for different diffusion
      coefficients and no nondiffusable buffer, predict that 1) the time course of
      residual Ca2+ is very brief, 2) an unrealistically low Ca2+ diffusion coefficient
      is required for residual calcium, 3) the spatially distributed Ca2+ signal is
      attenuated by intracellular BAPTA, 4) the rate at which free Ca2+ returns to
      resting levels, after entry (residual Ca2+) is faster with more mobile buffer,
      and 5) when pulse trains of Ca2+ channel current are used as input, computed
      facilitation is comparable to experimental measurements without buffer, but is
      abolished in the presence of exogenous buffer. 3. When the diffusion coefficient
      of Ca2+ in water is used, there is no residual Ca2+; however, when 0.1-1.6 mM
      nondiffusable buffer is present with a fast binding coefficient comparable to
      BAPTA, there is a very small residual Ca2+ due to the unbinding from the fixed
      binding sites. The nondiffusable buffer is saturated next to a Ca2+ channel. For
      this case of the diffusion coefficient of calcium in H2O and nondiffusable
      buffer, when a moderate amount of diffusable buffer is added to the system
      containing nondiffusable buffer, the very small residual Ca2+ is substantially
      reduced. This is because the product of diffusable buffer and Ca2+ is carried
      away as diffusable product, in contrast to the nondiffusable product releasing
      Ca2+, after Ca2+ entry ceases. 4. The model predicts that mobile calcium buffers
      with appropriate physical properties will attenuate facilitation and hasten its
      decay by removing residual calcium.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7823102
TI  - Activity of multiple identified motor neurons recorded intracellularly during
      evoked feedinglike motor programs in Aplysia.
AB  - 1. The firing patterns of 22 motor neurons were determined by simultaneously
      recording intracellularly from up to 7 neurons during evoked feedinglike buccal
      motor programs (BMPs). Intracellular stimulation of cerebral-buccal interneuron 2
      (CBI-2) or tactile stimulation of the odontophore were used to elicit BMPs in a
      reduced preparation. 2. Evoked BMPs were identified as either ingestive-like
      (iBMP) or egestive-like (eBMP) on the basis of their similarity to those
      previously recorded in select neurons in freely behaving animals. Neurons were
      divided into the p-group, r-group, or c-group, on the basis of the phase
      relationships of rhythmic membrane depolarizations and hyperpolarizations during
      evoked BMPs. Depolarization of the p-, r-, and c-group neurons was associated
      with radular protraction, retraction, and closure, respectively. With one
      exception, the motor neurons segregated into the same groups during iBMPs and
      eBMPs. The exception, B7, was categorized as a c-group neuron during iBMPs, but
      as an r-group neuron during eBMPs. 3. Every motor neuron exhibited cyclic
      membrane depolarizations and hyperpolarizations, and over one-half of the neurons
      fired bursts of action potentials, during both iBMPs and eBMPs. The neurons fired
      in patterns that would be likely to release both their conventional and peptide
      transmitters. 4. A marked hyperpolarizing step in the p-group neurons coincident
      with a depolarization in the r-group neurons was observed during both iBMPs and
      eBMPs, suggesting a degree of shared premotor circuitry for the two BMPs. 5. A
      shift in the timing of activity in c-group neurons relative to that in p- and r
      group neurons during iBMPs and eBMPs was observed and correlates well with the
      shift in phase of radular closure relative to protraction and retraction, which
      is useful in distinguishing ingestion from egestion in the behaving animal. 6.
      The firing patterns recorded in neurons that innervate overlapping populations of
      muscle fibers suggested that there would be complex interactions of multiple
      transmitters. This is particularly intriguing in the case of I3a muscle fibers,
      which are innervated by two excitatory and one inhibitory neuron. The firing
      patterns recorded in these neurons suggest that the inhibitory motor neuron may
      serve to not only block inappropriate contractions, but also to specifically
      shape evoked contractions during feeding.

PMID- 7823103
TI  - Coupling of spinal locomotor networks in larval lamprey revealed by receptor
      blockers for inhibitory amino acids: neurophysiology and computer modeling.
AB  - 1. Receptor blockers for inhibitory amino acids were applied to part or all of
      the spinal cord of larval lamprey during brain stem-initiated locomotor activity.
      Blocking glycinergic inhibition with strychnine applied to the entire spinal cord
      converted the locomotor pattern from left-right alternation to synchronous left
      right bursting. The results suggest that left and right oscillators are connected
      by relatively strong reciprocal inhibitory (glycinergic) connections in parallel
      with weaker reciprocal excitatory connections. This possible organization was
      supported by results from a computer model consisting of left and right
      oscillators connected by reciprocal inhibition and excitation in parallel. In
      addition, the results suggest that reciprocal inhibition is not required for left
      right rhythmicity but rather is involved primarily with phasing of left-right
      activity. 2. Locally blocking glycinergic inhibition with strychnine in the
      rostral spinal cord resulted in synchronous left-right burst activity in that
      region of the cord as well as in more caudal areas of the cord in which
      reciprocal inhibition should still be functional. 3. Blocking glycinergic
      inhibition in the caudal spinal cord converted the pattern in that region of the
      cord to left-right synchronous activity. The effects in the ascending direction
      on the burst patterns in more rostral areas of the spinal cord were less than
      those mentioned above in the descending direction with application of strychnine
      to the rostral spinal cord. 4. With glycinergic inhibition or GABAergic
      inhibition blocked in the entire spinal cord, stable longitudinal coupling along
      the spinal cord persisted. This and the neurophysiology results mentioned above
      suggest that the main mechanism for longitudinal coupling between locomotor
      networks in adjacent regions of the spinal cord is ipsilateral excitatory
      connections and not crossed inhibitory connections. This possible organization
      was supported by results from a computer model, which consisted of a pair of
      oscillators in the more rostral and more caudal spinal cord that could be
      connected by various types of coupling schemes. 5. The neurophysiological data
      above suggest that ipsilateral, excitatory coupling is stronger in the descending
      direction than in the ascending direction. In the computer model, a dominant
      descending coupling is a necessary requirement to produce positive longitudinal
      phase lags.

PMID- 7823104
TI  - Distributed actions and dynamic associations in respiratory-related neuronal
      assemblies of the ventrolateral medulla and brain stem midline: evidence from
      spike train analysis.
AB  - 1. Considerable evidence indicates that neurons in the brain stem midline and
      ventrolateral medulla participate in the control of breathing. This work was
      undertaken to detect and evaluate evidence for functional links that coordinate
      the parallel operations of neurons distributed in these two domains. 2. Data were
      from 51 Dial-urethan-anesthetized, bilaterally vagotomized, paralyzed,
      artificially ventilated cats. Planar arrays of tungsten microelectrodes were used
      to monitor simultaneously spike trains in two or three of the following regions:
      n. raphe obscurus-n. raphe pallidus, n. raphe magnus, rostral ventrolateral
      medulla, and caudal ventrolateral medulla. Efferent phrenic nerve activity was
      recorded to indicate the phases of the respiratory cycle. Electrodes in the
      ventral spinal cord (C3) were used in antidromic stimulation tests for spinal
      projections of neurons. 3. Spike trains of 1,243 neurons were tested for
      respiratory modulated firing rates with cycle-triggered histograms and an
      analysis of variance with the use of a subjects-by-treatments experimental
      design. Functional associations were detected and evaluated with cross
      correlograms, snowflakes, and the gravity method. 4. Each of 2,310 pairs of
      neurons studied included one neuron monitored within 0.6 nm of the brain stem
      midline and a second cell recorded in the ventrolateral medulla; 117 of these
      pairs (5%) included a neuron with a spinal projection, identified with antidromic
      stimulation methods, that extended to at least the third cervical segment. Short
      time scale correlations were detected in 110 (4.7%) pairs of neurons. Primary
      cross-correlogram features included 40 central peaks, 47 offset peaks, 4 central
      troughs, and 19 offset troughs. 5. In 14 data sets, multiple short-time scale
      correlations were found among three or more simultaneously recorded neurons
      distributed between both midline and ventrolateral domains. The results suggested
      that elements of up to three layers of interneurons were monitored
      simultaneously. Evidence for concurrent serial and parallel regulation of impulse
      synchrony was detected. Gravitational representations demonstrated respiratory
      phase dependent synchrony among neurons distributed in both brain stem regions.
      6. The results support a model of the brain stem respiratory network composed of
      coordinated distributed subassemblies and provide evidence for several
      hypotheses. 1) Copies of respiratory drive information from rostral ventrolateral
      medullary (RVLM) respiratory neurons are transmitted to midline neurons. 2)
      Midline neurons act on respiratory-related neurons in the RVLM to modulate phase
      timing. 3) Impulse synchrony of midline neurons is influenced by concurrent
      divergent actions of both midline and ventrolateral neurons.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 7823105
TI  - Calcium-dependent potassium channels play a critical role for burst termination
      in the locomotor network in lamprey.
AB  - 1. The possible involvement of calcium-dependent potassium channels (KCa) in the
      termination of locomotor bursts was investigated by administration of a specific
      blocker, apamin, in the lamprey spinal cord in vitro. The effects were examined
      by recording the efferent activity in ventral roots and by intracellular
      recording from interneurons and motoneurons. During fictive locomotion induced by
      N-methyl-D-aspartate (NMDA), apamin was found to affect both the frequency of
      bursting and the regularity of the locomotor pattern. 2. At the single cell
      level, NMDA can induce pacemaker-like membrane potential oscillations in
      individual neurons after administration of tetrodotoxin. Apamin (2.5 microM)
      produced a marked increase of the duration of the depolarizing plateau phase
      occurring during these NMDA-induced oscillations; this shows that the
      repolarization of the plateau is initiated by a progressive activation of apamin
      sensitive KCa-channels. 3. The action potential is followed by an
      afterhyperpolarization (AHP) with a fast and a slow phase (sAHP). The latter is
      known to be caused by apamin-sensitive KCa-channels. During repetitive firing,
      the interspike interval is dependent on the amplitude and the duration of the
      sAHP. Apamin caused a reduction of the spike frequency adaptation with a
      concomitant increase in the firing frequency. In some cells, apamin in addition
      reduced the threshold for the action potential. Apamin-sensitive KCa-channels
      thus will be involved in controlling both the onset and the duration of neuronal
      firing in the lamprey spinal cord. 4. During fictive locomotion induced by NMDA
      (40-200 microM), a blockade of KCa-channels by apamin produced an increase of the
      coefficient of variation (mean = 167%, n = 26), which was statistically
      significant in 21 out of 26 experiments. At 40-150 microM NMDA, an average
      increase in cycle duration was 77% and statistically significant in 15 out of 20
      preparations. At 200 microM NMDA (corresponding to higher burst rate), on the
      other hand, the average increase was only 6% and the increase was statistically
      significant in only 1 out 6 cases. For a given experiment, the strength of the
      apamin effect depended on the level of NMDA drive used, being more pronounced at
      slow rhythms, when it often caused a complete disruption of the locomotor
      pattern. At high burst rates, however, the cycle duration was less affected and a
      disruption of the regular burst pattern did not occur.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7823106
TI  - Endogenous bursts underlie seizurelike activity in solitary excitatory
      hippocampal neurons in microcultures.
AB  - 1. I compared the relative contributions of synaptic potentials and endogenous
      bursting to seizurelike activity in a simple model system. The system consisted
      of a solitary excitatory hippocampal rat neuron in a microculture. Each solitary
      excitatory neuron was grown in kynurenate and elevated magnesium and had
      excitatory autapses. 2. In normal physiological solution most neurons displayed
      the characteristic type of interictal epileptiform activity, the paroxysmal
      depolarizing shift (PDS). A minority of neurons displayed ictuslike epileptiform
      activity consisting of runs of PDSs with a sustained neuronal depolarization. 3.
      I analyzed the synaptic and nonsynaptic components underlying these forms of
      epileptiform activity. The synaptic and calcium current components of the
      epileptiform activity were removed by using a "synapse blocking solution" in
      which calcium was replaced with magnesium, and glutamate receptor activity was
      blocked using the glutamate antagonists 2-amino-5-phosphonovalerate and 6-cyano-7
      nitroquinoxaline-2,3-dione. Neurons that had only PDSs in normal physiological
      solution typically displayed only one or two action potentials in this synapse
      blocking solution. In contrast, neurons that had sustained depolarizations in
      normal physiological solution generally displayed bursts of action potentials in
      the synapse blocking solution, and some of the bursts had plateau depolarizations
      that lasted as long as several seconds. 4. The seconds-long endogenous plateau
      depolarizations were suppressed by tetrodotoxin, indicating involvement of
      persistent sodium currents. 5. The plateau depolarizations were shortened or
      abolished by 8 microM phenytoin, but there was only a small effect of phenytoin
      on nonplateau sustained repetitive firing of action potentials. 6. Elevation of
      extracellular potassium to 8 mM typically intensified the endogenous activity,
      usually converting action potential bursts to bursts with plateaus. 7. This study
      demonstrates that a sodium-dependent endogenous bursting underlies ictuslike
      epileptiform activity in this model system of seizurelike activity. The ability
      of phenytoin to attenuate this endogenous bursting suggests that a similar
      mechanism might underlie epileptiform bursting in less reduced systems such as
      brain slices or intact animals.

PMID- 7823107
TI  - Organization of single motor units in feline sartorius.
AB  - 1. We depleted single motor units in feline sartorius muscles of glycogen by
      stimulating their motoneurons intracellularly. We mapped the intramuscular
      distribution of depleted fibers by inspecting histological cross-sections
      throughout the length of sartorius. 2. We selected ten depleted motor units for
      detailed study and quantitative analysis. Nine motor units were located in the
      anterior head of sartorius. One was located in a muscle whose distal half
      appeared to have been damaged some time before the acute experiment. A single
      motor unit was located in the medial head of sartorius. 3. Five motor units were
      composed of fast-twitch glycolytic (FG) muscle fibers, two of fast-twitch
      oxidative glycolytic (FOG) muscle fibers, and three of slow-twitch oxidative (SO)
      muscle fibers. Estimates of the numbers of depleted fibers in motor units of
      anterior sartorius indicated that FG motor units were larger (mean 566 fibers)
      than FOG and SO motor units (SO mean 190, FOG mean 156 fibers). The SO motor unit
      in the damaged muscle had 550 fibers. One motor unit depleted in the medial head
      of sartorius had 270 fibers with FG profiles. 4. Muscle fibers belonging to each
      anterior motor unit were never distributed throughout the whole cross-section of
      anterior sartorius at any proximodistal level. Furthermore, fibers were
      distributed nonuniformly along the proximodistal axis of the muscle. In most
      muscles at least a few depleted fibers were found at all proximodistal levels.
      However, in one normal muscle and the damaged muscle, depleted fibers were
      confined to the proximal end. 5. The fibers in the medial motor unit were
      confined to a strip that did not extend across the whole cross-section of the
      muscle head. Fibers within this strip were scattered quite evenly from origin to
      insertion. This medial FG motor unit occupied a smaller territory and contained
      fewer fibers than anterior motor units of the same histochemical type. 6. These
      results show that sartorius motor units are not distributed uniformly in the
      mediolateral plane; those in anterior sartorius were distributed asymmetrically
      in the proximodistal axis as well. This finding has important functional
      implications for the way in which we model force development and transmission in
      sartorius and other long muscles.

PMID- 7823109
TI  - Serotonin has different effects on two classes of Betz cells from the cat.
AB  - 1. Intracellular recording from cat Betz cells in vitro revealed a strong
      correlation between the dominant effect of serotonin (5-HT) and the Betz cell
      subtype in which it occurred. In large Betz cells that show posthyperpolarization
      excitation (termed PHE cells), 5-HT evoked a long-lasting membrane
      depolarization, whereas 5-HT evoked an initial hyperpolarization of variable
      duration in smaller Betz cells that show posthyperpolorization inhibition (termed
      PHI cells). 2. Voltage-clamp studies revealed that 5-HT caused a depolarizing
      shift of activation of the cation current Ih, which resulted in the
      depolarization in PHE cells, whereas the hyperpolarization in PHI cells is caused
      by an increase in a resting potassium conductance. 3. The effect of 5-HT on
      firing properties during constant current stimulation also differed consistently
      in the two types of Betz cells. In PHE cells the initial firing rate increased
      after 5-HT application, but the steady firing was unaffected. The depolarizing
      shift of Ih activation caused the increase of initial firing rate. 4. In PHI
      cells 5-HT caused a decrease in spike frequency adaptation. The decrease in
      adaptation was caused by a combination of two conductance changes. First, 5-HT
      caused a slow afterdepolarization in PHI cells that could trigger repetitive
      firing in the absence of further stimulation. The sADP depended on calcium entry
      through voltage-gated channels and was associated with a decrease in membrane
      conductance. Second, 5-HT caused reduction of a slow calcium-dependent potassium
      current that normally contributes to slow adaptation. 5. In conclusion, the
      effect of 5-HT on excitability differs systematically in Betz cell subtypes in
      part because they have different dominant ionic mechanisms that are modulated. If
      we assume that PHE cells and PHI cells represent fast and slow pyramidal tract
      (PT) neurons respectively, 5-HT will cause early recruitment of fast PT cells and
      delay recruitment of slow PT cells during low levels of synaptic excitation.

PMID- 7823108
TI  - Neuromuscular regeneration by buccal motoneuron B15 after peripheral nerve crush
      in Aplysia californica.
AB  - 1. We studied regeneration of neuromuscular connections by identified buccal
      motoneuron B15 after axotomy produced by crushing nerve 4; the intact
      contralateral nerve 4 served as control. Electrophysiological recordings,
      intracellular dye injections, and light and electron microscopy were used to
      characterize the nature and time course of neuromuscular reinnervation as well as
      the fate of the isolated distal stump of the motor axon. 2. Axonal outgrowth or
      sprouting in the form of numerous "regenerites" occurred from the proximal stump
      of the transected B15 axon, and these regenerites projected through the crush
      site along the length of the nerve to innervate target muscles at the periphery.
      3. Reinnervation of one of the target muscles, the accessory radula closer (I5),
      was first detected 3 wk after nerve crush. Neuromuscular excitatory postsynaptic
      potentials measured in individual I5 muscle fibers were initially small and
      approached control amplitudes by 8 wk postlesion. Newly regenerated neuromuscular
      synapses displayed facilitation and depression to repeated B15 stimulation with
      properties similar to those of control synapses, even at early times postlesion.
      4. Reinnervation of other buccal muscles by B15, such as I4, appeared slightly
      delayed relative to that observed for I5. No evidence of abnormal or enlarged
      fields of innervation were observed, and as in control preparations, regenerated
      neuromuscular connections were strictly limited to muscles ipsilateral to the B15
      cell body. 5. Physiological evidence suggested that the distal axon stumps of
      B15, although isolated from their cell bodies, survive for several weeks after
      axotomy. In addition, several large axon profiles indicative of motor axons were
      seen in cross-sections of nerve 4 taken close to the muscle and distal to the
      crush site, indicating survival of distal axon stumps. 6. When B15 was
      selectively stimulated, the newly formed regenerites failed to fire the distal
      axon stump of B15, demonstrating that the regenerites do not reinnervate the
      distal stump. 7. Degeneration of axons in nerve 4 distal to the crush site was
      observed in cross-sections of the nerve at 8 wk postlesion; using ultrathin
      sections we found cellular debris in individual axon profiles as well as large
      acellular masses within nerve 4, the latter likely representing the concretion of
      many axons. Additional evidence for such degenerative changes appeared in the
      form of autofluorescing spherical bodies or "spheroids" both in individual axons
      and the nerve distal to the crush site.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7823110
TI  - Properties of the sodium current in rat chromaffin cells exposed to nerve growth
      factor in vitro.
AB  - 1. This paper examines the electrophysiological properties of cultured rat
      adrenal chromaffin cells at different stages of neuron-like morphological
      differentiation in response to nerve growth factor (NGF). 2. Chromaffin cells
      display a large variability in the morphological changes after exposure to NGF.
      However, a marked tendency to neuronal phenotypic transformation prevails after
      two weeks in culture. 3. The voltage dependence of the macroscopic Na currents,
      judged by the current to voltage relationship, did not change significantly as a
      result of NGF treatment. Moreover, when kinetics, half-activation, and half
      inactivation parameters of Na currents were compared between control and NGF
      treated cells, no significant differences were observed. 4. Peak Na currents in
      control cells remained < 1 nA throughout the 17 d of observation, whereas
      currents > 1 nA became more frequent after the first week of NGF exposure. Cells
      with Na currents > 2 nA were found routinely in cultures exposed to NGF for > or
      = 15 d, but inadequate voltage control and neurite spiking prevented a thorough
      examination. Sodium current density in the population of NGF-treated chromaffin
      cells increased progressively over time, until an apparent plateau (3.5-fold
      increase) was reached by the end of the second week. No significant changes were
      observed in control, untreated cells. 5. The increase in Na channel density
      induced by NGF in chromaffin cells in compatible with the acquisition of the
      neuronal phenotype. Interestingly, the increase in Na channel expression occurs
      in slower time scale than in their neoplastic correlate, the PC12 cells. Na
      channels newly expressed by chromaffin cells after NGF treatment are functionally
      indistinguishable from those already present before treatment.

PMID- 7823111
TI  - Cross-correlation analysis of cuneothalamic interactions in the rat somatosensory
      system: influence of receptive field topography and comparisons with
      thalamocortical interactions.
AB  - 1. We simultaneously recorded neuronal responses to cutaneous stimulation from
      matched somatotopic representations in the nucleus cuneatus and ventrobasal
      complex of intact, halothane-anesthetized rats. A total of 95 cuneate and 86
      thalamic neurons representing hairy skin on the forelimb were activated by hair
      movements produced by air jets at multiple skin sites. Mean responsiveness was
      higher among neurons in nucleus cuneatus (34.4 spikes per stimulus) than in
      thalamus (23.7 spikes per stimulus), a result that was consistent with the
      greater proportion of "sustained" responses recorded in nucleus cuneatus (80%)
      than in the thalamus (62%). 2. Cross-correlation analysis of 166 pairs of cuneate
      and thalamic neurons showed that 56 neuron pairs displayed time-locked
      correlations in activity that were characterized primarily by excitatory
      interactions (44 pairs) or a combination of excitatory and inhibitory
      interactions (10 pairs). Unilateral interactions in the cuneothalamic direction
      (31 pairs) and reverse direction (11 pairs) were observed, as well as multiphasic
      interactions in both directions (14 pairs). Most excitatory interactions involved
      intervals of 1-7 ms between successive cuneate and thalamic discharges, whereas
      most inhibitory influences involved intervals > 7 ms. Connection strength,
      defined by the ratio of time-linked interactions to the number of cuneate
      discharges, varied widely among neuron pairs but was largest for interactions
      involving interspike intervals of < or = 15 ms. 3. The relationship between
      connection strength and receptive field topography was analyzed in 103 cuneate
      thalamic neuron pairs. The region of skin shared by both neurons varied
      substantially among neuron pairs and the probability of detecting interactions
      increased proportionately with larger amounts of receptive field overlap. Neuron
      pairs with moderate (25-50%) amounts of receptive field overlap had connection
      strengths 3-4 times greater than neuron pairs with minimal (0-25%) overlap.
      Connection strength was essentially identical, however, for neuron pairs with
      moderate or large (> 50%) amounts of overlap. 4. Cuneate-thalamic neuron pairs
      displaying functional connections were usually tested at multiple peripheral
      sites, but only 37% (18 of 49) of these neuron pairs displayed interactions at
      more than one stimulation site. Stimulation at different sites altered the timing
      of interactions in seven neuron pairs, including three that showed timing shifts
      across time zero in the cross-correlation histogram. In neuron pairs displaying
      interactions at multiple sites, connection strengths for 67% of the cases were
      strongest when stimulation was delivered within the region of receptive field
      overlap.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7823112
TI  - Properties of neuroprotective cell-permeant Ca2+ chelators: effects on [Ca2+]i
      and glutamate neurotoxicity in vitro.
AB  - 1. Cell-permeant Ca2+ chelators such as 1,2-bis-(2-amino-phenoxy)ethane-
      N,N,N',N'-tetraacetic acid acetoxymethyl ester (BAPTA-AM) protect neurons against
      excitotoxic and ischemic neuronal injury in vitro and in vivo. Here we provide
      the first steps toward characterizing the mechanisms by which these agents
      produce their neuroprotective effects. 2. Cultured mouse spinal neurons were
      simultaneously loaded with the Ca2+ indicator fura-2 and with one of three
      permeant chelators derived from the fast Ca2+ buffer BAPTA, or with ethylene
      glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid acetoxymethyl ester
      (EGTA-AM). Adding these chelators did not interfere with the fluorescence
      spectrum of fura-2 and had no effect on baseline [Ca2+]i. 3. The neurons were
      challenged with 250 microM L-glutamate for 50 min, producing a marked transient
      [Ca2+]i increase followed by a decay of [Ca2+]i to a lower "plateau." About 80%
      of control neurons succumbed to this excitotoxic insult. Neurons that survived
      adjusted their plateau [Ca2+]i to lower levels than those that succumbed. 4.
      Neurons that were pretreated with permeant Ca2+ chelators became more resistant
      to these neurotoxic challenges. 5. We examined whether this reduction in
      glutamate neurotoxicity could be related to the given buffer's known Ca2+
      affinity (Kd), its Ca2+ binding kinetics, and its ability to attenuate glutamate
      induced [Ca2+]i increases. 6. Pretreatment of neurons with BAPTA analogues having
      Kds ranging from 100 to 3,600 microM 1) attenuated the amplitude and 2)
      lengthened the time constant describing the rise and decay of the glutamate
      evoked [Ca2+]i transient. The magnitude of these effects paralleled the affinity
      of the chelator for Ca2+. 7. BAPTA-AM and its analogues dramatically attenuated
      the early neurotoxicity of glutamate, reducing cell deaths by up to 80%. However,
      in contrast with the graded effects of chelators having different Ca2+ affinities
      on Ca2+ transients, all BAPTA analogues were equally protective. These protective
      effects did not relate to the chelators' Ca2+ affinity within a Kd range of 100
      nM (for BAPTA) to 3,600 nM (for 5,5'-dibromo BAPTA). 8. BAPTA-AM protected
      neurons in a concentration-dependent manner with 50% protection obtained with 10
      microM, a concentration having no effect on the [Ca2+]i transient amplitude. 9.
      EGTA, a slow Ca2+ buffer with a similar Ca2+ affinity to BAPTA produced the same
      effects as BAPTA on [Ca2+]i transient kinetics. However, it was far less
      protective than BAPTA. 10. The time course of early glutamate neurotoxicity was
      altered by the BAPTA analogues, but not EGTA. BAPTA analogues caused a small
      increase in cell deaths in the first minutes of each experiment, followed by
      relative sparing from further neurodegeneration. 11. The ability of low Ca2+
      affinity chelators such as 5,5'-dibromo BAPTA to protect neurons without markedly
      attenuating measured [Ca2+]i increases conflicts with the hypothesis that global
      elevations in [Ca2+]i are responsible for triggering neurotoxicity.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7823113
TI  - Oscillatory synaptic interactions between ventroposterior and reticular neurons
      in mouse thalamus in vitro.
AB  - 1. The thalamic reticular nucleus (RTN) has reciprocal connections with relay
      neurons in the dorsal thalamus. We used whole cell recording in a mouse in vitro
      slice preparation maintained at room temperature to study the synaptic
      interactions between the RTN and the ventroposterior thalamic nucleus (VP) during
      evoked low-frequency oscillations. 2. After a single electrical stimulus of the
      internal capsule, postsynaptic potentials (PSPs) were recorded in all VP and RTN
      neurons. In 76% of slices, there was an initial response followed by recurrent
      PSPs lasting for up to 8 s and with a frequency of approximately 2 Hz in both the
      VP and RTN. 3. In RTN neurons the initial response consisted of a fast excitatory
      postsynaptic potential (EPSP) that generated a burst of action potentials.
      Recurrent PSPs consisted of barrages of EPSPs that often reached burst threshold.
      The structure of subthreshold EPSP barrages in RTN neurons suggested that they
      were generated by bursting VP neurons. 4. In VP neurons the stimulus usually
      evoked a small EPSP followed by a large inhibitory postsynaptic potential (IPSP)
      that was often followed by a rebound burst. This initial response was often
      followed by a series of recurrent IPSPs presumably generated by RTN bursts,
      because intrinsic inhibitory neurons are absent in rodent VP. 5. IPSPs in VP
      neurons and recurrent EPSPs in RTN neurons were completely abolished by
      application of a gamma-aminobutyric acid-A (GABAA) receptor antagonist. A GABAB
      receptor antagonist produced no or little change in either the initial or
      recurrent response. 6. Recurrent IPSPs in VP neurons were abolished by glutamate
      receptor antagonists before the initial IPSP, which always remained stimulus
      dependent. 7. The dependency of recurring IPSPs in VP and recurring EPSPs in RTN
      upon GABA-mediated inhibition and excitatory amino acid-mediated excitation, plus
      the character of recurring EPSPs in the RTN strongly suggest that the recurring
      events were generated through reverse-reciprocal synaptic interactions between VP
      and RTN neurons. These synaptic interactions most likely play an important role
      in thalamic oscillations in behavior.

PMID- 7823114
TI  - Effect of neck posture on the activation of feline neck muscles during voluntary
      head turns.
AB  - 1. To determine whether neck posture affects the usage of neck muscles during a
      specific motor task, we recorded the electromyographic (EMG) patterns of neck
      muscles in four cats, which made horizontal, head-turning movements to fixate
      eccentrically placed targets. In some trials, the cervical column was oriented
      vertically whereas in other trials, the cervical column was oriented more
      horizontally. 2. During horizontal head movements, five muscles (obliquus capitis
      inferior, splenius, levator scapulae, complexus, and biventer cervicis) displayed
      activation patterns that were consistent from cat to cat and did not change when
      the cats adopted a different neck posture. Most of these muscles are large,
      superficial muscles that attach to the skull and span many cervical joints. 3.
      Posturally dependent patterns of activation were observed in five other neck
      muscles (semispinalis cervicis, longissimus capitis, levator scapulae ventralis,
      scalenus anterior, and obliquus capitis superior). Most of these muscles lie
      deeper and more laterally within the neck musculature and generally span fewer
      cervical joints than the muscles that displayed invariant patterns of activation.
      4. These results suggest that the set of invariantly activated muscles may
      compose part of a basic motor program that is triggered during head movements in
      the horizontal plane. This motor program appears to be modified by the selective
      activation of ancillary muscles, which are recruited in a manner related to the
      neck posture. The deep positioning of the ancillary muscles may permit them to
      regulate the mobility of the cervical column and to adjust the net muscular force
      applied across the neck to the skull. Organizing the motor output in this manner
      might simplify the task of computing the appropriate patterns of neck-muscle
      activation.

PMID- 7823115
TI  - A cephalothoracic command system controls stridulation in the acridid grasshopper
      Omocestus viridulus L.
AB  - 1. In the acridid grasshopper Omocestus viridulus, I performed intracellular
      recording and stimulation of descending brain neurons simultaneously with the
      recording of the stridulatory hindleg movements in a minimally dissected
      preparation. The descending B-DC-3 interneurons were identified with
      intracellular staining techniques. In each half of the brain at least two sibling
      B-DC-3 interneurons exist. Main features of the neurons are a medial soma
      position and a pronounced dendritic arborization within the medial dorsal
      posterior protocerebrum. The axon descends contralaterally and occupies an
      extreme medial position in the cervical and thoracic connectives. 2. The
      occurrence of stridulatory behavior is strictly coupled with tonic spike activity
      in the B-DC-3 interneurons. During spontaneous stridulation these interneurons
      discharge action potentials at a rate of approximately 100 action potentials per
      second. 3. Individual B-DC-3 interneurons are sufficient to initiate and maintain
      the species-specific leg movements of courtship stridulation. During gradual
      depolarization stridulation is elicited at discharge rates of approximately 70
      action potentials per second. On pulselike depolarization the neurons show a
      phasic-tonic discharge pattern. 4. The interneurons are necessary for the
      generation of stridulatory leg movements. Inhibition of an individual B-DC-3
      interneuron can stop spontaneous stridulatory motor activity. 5. Depolarization
      of an individual B-DC-3 interneuron during ongoing spontaneous stridulation
      increases the repetition rate and amplitude of the stridulatory leg movements.
      Thus the B-DC-3 interneurons can also modulate the output of the stridulatory
      pattern generator. 6. Because of their number, structure, and properties, the B
      DC-3 interneurons have to be regarded as the command system of stridulation in
      the acridid grasshopper O. viridulus.

PMID- 7823116
TI  - Dissociation between perception and visuomotor transformation during reproduction
      of remembered distances.
AB  - 1. In complete darkness subjects were presented with two visual stimuli whose
      distance was randomly varied. The subjects were required to reproduce the
      interstimulus remembered distance in two conditions. In one condition
      (reproduction by pointing) they pointed to a virtual position in space. In the
      other condition (visual reproduction) they used two other visual stimuli. One of
      them was fixed, and the other could be manually moved. Constant and variable
      errors were measured in the two conditions. 2. Constant error varied between the
      two conditions. In the pointing task subjects slightly overestimated the shorter
      distances, and underestimated the longer ones. During visual reproduction, they
      consistently overestimated all distances, and the error of overestimation tended
      to increase with distance. Statistical comparison between the errors in the two
      conditions was significant. Variable error increased with distance in both
      conditions, but did not show any significant difference between the two tasks. 3.
      The results of the present experiment support the hypothesis that perception and
      visuo-motor transformation are two separate processes in which the same object
      attributes are independently analysed. However, the finding that variable error
      did not change between the two tasks suggests that some stages are common to the
      two processes.

PMID- 7823117
TI  - A novel cholinergic induction of long-term potentiation in rat hippocampus.
AB  - 1. We studied long-term cholinergic effects on synaptic transmission in submerged
      hippocampal slices using intra- and extracellular recording techniques. 2. Bath
      application of submicromolar concentrations of carbachol (CCh) produced a
      gradually developing, long-lasting increase in the CA1 excitatory postsynaptic
      potential and population spike. This potentiation was blocked by atropine and,
      hence, named muscarinic long-term potentiation (LTPm). Application of DL-2-amino
      5-phosphonovaleric acid had no effect on LTPm, indicating that this phenomenon is
      N-methyl-D-aspartate receptor independent. 3. These effects of CCh were not
      likely to be due to the blockade of one of several K+ conductances by the drug;
      the time and concentration dependence of LTPm were different from those
      associated with cholinergic blockade of K+ conductances. 4. Removal of
      extracellular calcium (Cao2+) from the bath blocked synaptic transmission. CCh
      added in calcium-free medium induced LTPm, which was revealed upon removal of the
      drug by washing with normal calcium-containing medium. Neither cutting CA1-CA3
      connections nor cessation of synaptic stimulation interfered with LTPm induction.
      5. Application of thapsigargin or H-7 together with CCh blocked LTPm, suggesting
      the involvement of intracellular calcium (Cai2+) stores and protein kinases,
      respectively, in the LTPm mechanism. 6. Subthreshold cholinergic stimulation
      coupled with subthreshold tetanic stimulation caused LTP. CCh had no effect when
      administered after the LTP mechanism had been saturated by repeated
      suprathreshold tetani. Tetanic stimulation failed to cause LTP when applied after
      LTPm had been induced by CCh. These experiments indicate that tetanus-induced
      potentiation and LTPm share a common mechanism and provide a direct link between
      ACh and mechanisms of synaptic plasticity.

PMID- 7823118
TI  - Botulinum neurotoxin alters the discharge characteristics of abducens motoneurons
      in the alert cat.
AB  - 1. The effects of botulinum neurotoxin (BoTx) injected into the lateral rectus
      muscle were examined in alert cats by recording the extracellular activity of
      abducens motoneurons during spontaneous eye movements. 2. A single high dose (3
      ng/kg) of BoTx produced a complete paralysis of abduction that lasted for more
      than 2 mo. In addition, changes were found in the discharge pattern of abducens
      motoneurons. Motoneurons discharged steadily at a low firing rate (15-50
      spikes/s), which in some instances showed a complete independence of eye
      position. Their increases in activity during ON-directed saccades were markedly
      reduced with respect to controls. The loss of inhibitory signals for OFF-directed
      saccades was even more evident. 3. A low dose (0.3 ng/kg) of BoTx also produced a
      paralysis of the lateral rectus muscle that lasted for approximately 1 mo. In
      this case, only minor modifications in the firing characteristics of abducens
      motoneurons were observed. 4. The present findings indicate that the effects of
      BoTx observed in the discharge pattern of abducens motoneurons might be due not
      only to target disconnection, but also to a central action of the neurotoxin on
      the motoneuron.

PMID- 7823119
TI  - Simple spike responses of gaze velocity Purkinje cells in the floccular lobe of
      the monkey during the onset and offset of pursuit eye movements.
AB  - 1. We recorded the simple spike firing rate of gaze velocity Purkinje cells (GVP
      cells) in the flocculus/ventral paraflocculus of two monkeys during the smooth
      pursuit eye movements evoked by a target that was initially at rest, started
      suddenly, moved at a constant velocity, and then stopped. 2. For target motion in
      the preferred direction, GVP-cells showed a large transient increase in firing
      rate at the onset of pursuit, a smaller but sustained increase during the
      maintenance of pursuit, and a smooth return to baseline firing with little
      undershoot at the offset of pursuit. For target motion in the nonpreferred
      direction, GVP-cells showed a small decrease in firing rate at the onset of
      pursuit, a similar sustained decrease during the maintenance of pursuit, but a
      large transient increase in firing rate at the offset of pursuit before returning
      to baseline firing. 3. We pooled the data in our sample of horizontal GVP-cells
      by subtracting the population average of firing rate recorded during pursuit in
      the nonpreferred direction from the population average recorded during pursuit in
      the preferred direction. We transformed this net population average by passing it
      through a model of the brain stem final common pathway and the oculomotor plant.
      This yielded a signal that closely matched the observed trajectory of eye
      velocity during pursuit. We conclude that the transient overshoots exhibited in
      the firing rate of GVP-cells can provide appropriate compensation for the lagging
      dynamics of the oculomotor plant.

PMID- 7823120
TI  - Morphological analysis of dendritic spine development in primary cultures of
      hippocampal neurons.
AB  - We monitored developmental alterations in the morphology of dendritic spines in
      primary cultures of hippocampal neurons using confocal laser scanning microscopy
      (CLSM) and the fluorescent marker Dil. Dissociated rat hippocampal neurons were
      plated on polylysine-coated glass cover slips and grown in culture for 1-4 weeks.
      Fixed cultures were stained with Dil and visualized with the CLSM. Spine density,
      spine length, and diameters of spine heads and necks were measured. Some cultures
      were immunostained for synaptophysin and others prepared for EM analysis. In the
      1-3 week cultures, 92-95% of the neurons contained spiny dendrites. Two
      subpopulations of spine morphologies were distinguished. At 1 week in culture,
      "headless" spines constituted 50% of the spine population and were equal in
      length to the spines with heads. At 2, 3, and 4 weeks in culture headless spines
      constituted a progressively smaller fraction of the population and were, on
      average, shorter than spines with heads. Spines with heads had narrower necks
      than headless spines. At 3 weeks in culture, spines were associated with
      synaptophysin-immunoreactive labeling, resembling synaptic terminals. At 4 weeks
      in culture, only 70% of the Dil-filled cells had spiny dendrites, and the density
      of spines decreased. Ultrastructurally, the majority of dendritic spine-like
      structures at 1 week resembled long filopodia without synaptic contacts. The
      majority of axospinous synapses were on short "stubby" spines. At 3 weeks in
      culture, the spines were characteristic of those seen in vivo. They contained no
      microtubules or polyribosomes, were filled with a characteristic, filamentous
      material, and formed asymmetric synapses. These studies provide the basis for
      further analysis of the rules governing the formation, development, and
      plasticity of dendritic spines under controlled, in vitro conditions.

PMID- 7823121
TI  - Adoption reverses the long-term impairment in glucocorticoid feedback induced by
      prenatal stress.
AB  - The development of the organism is subjected to critical and complex influences
      during the perinatal period. Prenatal and postnatal stresses can have different
      long-term behavioral effects, and appropriate postnatal manipulations can
      counteract the behavioral effects of prenatal stress. In the present study, we
      investigated the involvement of changes in the activity of the hypothalamo
      pituitary-adrenal (HPA) axis in the long-term effects of prenatal and postnatal
      events and of interactions between them. We investigated stress-induced
      corticosterone secretion and hippocampal corticosteroid receptors in male adult
      rats submitted to prenatal and/or postnatal manipulations. Repeated restraint
      during the last week of pregnancy was used as prenatal stressor, and adoption at
      birth was used to change the postnatal environment. We found that (1) prenatal
      stress prolongs stress-induced corticosterone secretion in adult rats, which was
      attributed to the observed decrease in central corticosteroid receptors; (2)
      adoption, irrespective of the stress experience of the foster mother, reverses
      the effects of prenatal stress; and (3) adoption per se increases maternal
      behavior and decreases the stress-induced corticosterone secretion peak in the
      adult offspring. In conclusion, certain prenatal and postnatal manipulations
      appear to have opposite long-term effects on the activity of the HPA axis, and
      adoption, probably by modifying maternal behavior, can protect against the
      effects of prenatal stress. Thus, changes in the activity of the HPA axis may be
      one of the biological substrates of the long-term effects of certain perinatal
      events.

PMID- 7823122
TI  - Cytotoxic effects of sigma ligands: sigma receptor-mediated alterations in
      cellular morphology and viability.
AB  - The morphological effects of several neuroleptics as well as other novel and
      prototypic sigma ligands were examined by addition to cultures of C6 glioma
      cells. Sigma ligands caused loss of processes, assumption of spherical shape, and
      cessation of cell division. The time course and magnitude of this effect were
      dependent on the concentration of sigma ligand. Continued exposure to sigma
      compounds ultimately resulted in cell death. However, the morphological effect
      was reversible when sigma ligand was removed shortly after rounding. The potency
      of compounds to produce these effects generally correlated with binding affinity
      at sigma receptors of C6 glioma cell membranes labeled with [3H](+)-pentazocine.
      At a concentration of 100 microM, haloperidol, reduced haloperidol, fluphenazine,
      perphenazine, trifluoperazine, BD737, LR172, BD1008, and SH344 produced
      significant effects in 3-6 hr of exposure. Other compounds, such as
      trifluperidol, thioridazine, and (-)-butaclamol, produced significant effects by
      24 hr of exposure. Despite the requirement of micromolar concentrations of ligand
      (some compounds were effective at 30 microM), the effect showed a remarkable
      specificity for compounds exhibiting sigma receptor binding affinity.
      Neuroleptics lacking potent sigma affinity [e.g., (-)-sulpiride, (+)-butaclamol,
      and clozapine] and other compounds that lack significant sigma affinity but that
      are agonists or antagonists at dopamine, serotonin, adrenergic, glutamate,
      phencyclidine, GABA, opiate, or muscarinic cholinergic receptors were without
      effect on cellular morphology at concentrations up to 300 microM over a period of
      72 hr. Likewise, blockers and activators of Na+, K+, and Ca2+ channels and a
      monoamine oxidase inhibitor devoid of sigma affinity were without effect.
      Interestingly, 1,3-di-o-tolylguanidine (DTG), (+)-3-(3-hydroxyphenyl)-N-(1
      propyl)piperidine [(+)-3-PPP], (+)-pentazocine, (+)-cyclazocine, and other sigma
      active benzomorphans and morphinans appeared inactive in up to 72 hr of culture.
      However, these compounds interacted synergistically with a subeffective dose of
      BD737 (30 microM) to produce effects usually in 6 hr or less. Also, the pH of the
      culture medium had a profound effect on the activity of sigma compounds.
      Increasing the pH from the normal range of 7.2-7.4 to pH 8.3-8.5 shifted the dose
      curves (30, 100, 300 microM) for all sigma compounds to the left. Under these
      conditions, DTG, (+)-3-PPP, and benzomorphans produced effects in 24 hr or
      less.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7823123
TI  - Functional anatomical studies of explicit and implicit memory retrieval tasks.
AB  - Across three experiments, PET scans were obtained while subjects performed
      different word-stem completion and FIXATION control tasks designed to study the
      functional anatomy of memory retrieval. During each of three different word-stem
      completion scans, word-stem cues were visually presented in uppercase letters.
      The RECALL task required explicit retrieval of study words presented prior to the
      PET scan. The PRIMING task addressed the implicit effects of the prior study
      words without requiring intentional recall. The BASELINE task encouraged
      retrieval of information from a general knowledge store. Across experiments, the
      similarity between study words and word stems was manipulated by presenting
      prescan study words in either uppercase letters identical to the stems, in
      lowercase letters, or auditorily. The PRIMING task was not studied with auditory
      presentation. Many activations were consistent across experiments. The BASELINE
      task activated several regions in response to the reading and verbal-response
      demands of the task (visual, motor, and premotor cortices, cerebellum), as well
      as a left prefrontal region. The RECALL task additionally activated regions in
      anterior right prefrontal cortex. Bilateral occipitotemporal regions showed blood
      flow reductions during the PRIMING task as compared to the BASELINE task.
      Activation in the right hippocampal/parahippocampal region was observed only in
      one experiment, and no experiment showed activation in the left medial temporal
      lobe. These experiments suggest that areas of frontal cortex play a role in
      explicit recall and that an effect of priming may be to require less activation
      of perceptual regions for the processing of recently presented information.

PMID- 7823124
TI  - Facilitatory coupling between a glutamate metabotropic receptor and
      dihydropyridine-sensitive calcium channels in cultured cerebellar granule cells.
AB  - The effect of metabotropic glutamate receptor activation on Ca dihydropyridine
      (DHP)-sensitive channels recorded in the presence of 1 microM Bay K 8644 was
      examined on cultured cerebellar granule cells using the patch-clamp technique in
      the cell-attached configuration. Bath-applied agonist (trans-ACPD, 1S,3R-, and
      1R,3S-ACPD isomers, and glutamate or quisqualate in the presence of CPP and CNQX)
      evoked an increase in Ca channel activity with a variable latency of 8.9 +/- 8.6
      sec in 40% of the recorded cells. Neither L-CCG1, L-AP3, L-AP4, nor AMPA or NMDA
      activated Ca channels. Two dihydropyridine-sensitive channels present in this
      cell type were activated by trans-ACPD: the classical 24 pS L-type channel and a
      smaller-conductance 7 pS channel. The effect was shown to be mediated by neither
      intracellular Ca2+ nor a pertussis toxin (PTX)-sensitive G protein. Interestingly
      treatment with BAPTA-AM increased the number of responding patches and the
      activity was more sustained throughout the drug application. After overnight PTX
      treatment, activation of the Ca channels persisted even after washout of the
      agonist. These results indicate that mGluR1/mGluR5 probably mediate the
      facilitation of dihydropyridine-sensitive Ca channels.

PMID- 7823125
TI  - Cholinergic regulation of neurite outgrowth from isolated chick sympathetic
      neurons in culture.
AB  - Neurotransmitters have been reported to regulate neurite outgrowth in several
      vertebrate and nonvertebrate species. In this study, cultures of isolated
      embryonic day 12 (E12) chick sympathetic neurons were grown in the presence of
      cholinergic receptor agonists or antagonists. Both ACh and the nonhydrolyzable
      cholinergic agonist carbamylcholine (CCh) inhibited neurite outgrowth. ACh (0.1
      1.0 mM) decreased the percentage of neurons bearing neurites, but had no
      significant effect on cell survival. The effect of ACh was increased in the
      presence of the cholinesterase inhibitors BW284C51 (1 microM), Tacrine (20
      microM), and edrophonium (200 microM). Neurite outgrowth was strongly inhibited
      by the muscarinic receptor agonist oxotremorine (5-100 microM) and weakly
      inhibited by nicotine (50 nM to 10 microM). The inhibitory effect of CCh was
      decreased by the muscarinic receptor antagonist atropine (10 microM),
      demonstrating that the effect of CCh on neurite outgrowth was mediated, at least
      in part, through a muscarinic receptor. The possibility that AChE can influence
      neurite outgrowth directly, through a noncatalytic mechanism, was also examined.
      When dissociated chick brain or sympathetic neurons were grown on plates
      precoated with purified AChE, neurite outgrowth was strongly stimulated. However,
      the neurite outgrowth-promoting effect of AChE was strictly dependent upon the
      presence of substratum-bound heparan sulfate proteoglycans (HSPG). Pretreatment
      of AChE with diisopropylfluorophosphate to inhibit the esterase activity did not
      abolish this effect, suggesting that the neurite outgrowth-promoting effect of
      AChE was associated with a noncatalytic mechanism, a view supported by the
      observation that soluble AChE had no effect on neurite outgrowth.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7823126
TI  - Beta 2-adrenergic receptors are expressed by glia in vivo in the normal and
      injured central nervous system in the rat, rabbit, and human.
AB  - Previous studies have demonstrated that glial cells in culture express several
      subtypes of functional adrenergic receptors. To determine if similar receptors
      are expressed by glia in vivo, we examined the expression of adrenergic receptors
      in the normal, crushed, and transected optic nerves of the rabbit and rat using
      quantitative receptor autoradiography. Additionally, we examined the expression
      of adrenergic receptors in the normal and damaged human optic nerve. High levels
      of alpha 1-, alpha 2-, beta 1-, and beta 2-adrenergic receptors were identified
      in the rabbit and rat forebrain. In the normal rabbit, rat, and human optic
      nerves, only alpha 1 and beta 2 receptors were observed, and these were present
      in low to moderate densities. Combined immunohistochemistry and autoradiography
      suggests that the majority of beta 2-adrenergic receptors in the rabbit, rat, and
      human optic nerve are expressed by astrocytes. After unilateral optic nerve crush
      or transection, only beta 2- adrenergic receptors were significantly increased.
      This increase in beta 2 receptors was first detectable at days 7 and 28 post
      transection in the rabbit and rat, respectively. The expression of beta 2
      receptors in the transected optic nerve continued to increase with time, so that
      by 90 d post-transection the density of beta 2 receptors in both the rabbit and
      rat optic nerve was among the highest of any area in the forebrain. Taken
      together with previous studies, these results suggest that in vivo, beta 2
      adrenergic receptors may provide a therapeutic target for regulation of astrocyte
      functions including glycogen metabolism, cytokine release, and the hypertrophy
      and proliferation that occurs in response to neuronal injury.

PMID- 7823127
TI  - Perineurial defect and peripheral opioid analgesia in inflammation.
AB  - Opioid receptors have been demonstrated on sensory nerves in both inflamed and
      normal subcutaneous tissue but locally applied opioid agonists produce analgesia
      in inflamed tissue only. Inflammation confers a disruption of the perineurial
      barrier that can also be induced deliberately by hyperosmolar solutions. The
      present study examines at which stage of Freund's adjuvant-induced inflammation
      peripheral opioid analgesic effects become manifest and whether a perineurial
      defect contributes to the appearance of such effects. To this end we have
      monitored the temporal evolution of inflammatory signs (swelling, temperature,
      hyperalgesia) and of peripheral antinociceptive effects (by the paw pressure
      test) of mu-, delta-, and kappa-selective opioids. Using horseradish peroxidase
      histochemistry, the perineurial barrier was assessed in normal and inflamed
      tissue and following its artificial disruption by hyperosmolar saline and
      mannitol in vivo. Finally, we sought to elicit analgesia in normal tissue by the
      concomitant application of mannitol and receptor-selective opioids or by an
      extremely lipophilic opioid agonist (fentanyl). We found that peripheral opioid
      antinociception and perineurial leakage occur simultaneously at a very early
      stage (within 12 hr) of the inflammatory reaction and that both can be mimicked
      by the administration of hyperosmolar solutions in normal tissue. Fentanyl
      produced peripheral antinociception in noninflamed tissue that was potentiated by
      mannitol or inflammation. Our findings demonstrate that the perineurium is a
      crucial determinant for peripheral opioid analgesia and that the efficacy of
      locally applied hydrophilic or lipophilic neuromodulatory compounds can be
      improved dramatically by the concomitant modulation of perineurial
      permeability.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7823128
TI  - Influences of vestibular and visual motion information on the spatial firing
      patterns of hippocampal place cells.
AB  - Hippocampal place cells show location-specific firing as animals locomote in an
      environment. A possible explanation for these place fields is that each cell is
      simply driven by environmental sensory inputs available in its field. This cannot
      provide the full explanation, however, since cells can maintain stable place
      fields even in the absence of reliable environmental orienting cues. This
      suggests the cells are also influenced by movement-related information, since
      this is the only available, ongoing indicator of current location when external
      orienting cues are not present. Two candidates for the movement-related
      information are vestibular activation, and visual motion. To test for these
      influences, place cells were recorded as animals locomoted in a cylindrical
      apparatus that was made so that its wall (painted with vertical black and white
      stripes) and floor could be independently rotated, to provide visual motion and
      vestibular inputs, respectively. The results showed that both these inputs could
      influence place fields. Sometimes they caused a predictable locational shift, so
      that the field rotated its location on the apparatus floor in a way that was
      compatible with the movement indicated by the vestibular and/or visual motion
      input. This updating was most reliably obtained when the two inputs were
      presented in combination. In other cases, the apparatus rotations caused
      unpredictable changes in firing characteristics, so that cells either stopped
      firing, or developed place fields that were altered in overall size, shape, and
      eccentricity. Interestingly, the probability of these changes increased with
      experience with the rotational manipulations, suggesting a learned component.

PMID- 7823130
TI  - Differential regulation of neuronal sodium channel expression by endogenous and
      exogenous tyrosine kinase receptors expressed in rat pheochromocytoma cells.
AB  - The biological activity of growth factors that act through receptor tyrosine
      kinases (RTKs) can differ dramatically, depending on both the properties of the
      RTKs and the cellular environment in which the RTKs are expressed. To determine
      the ability of different RTKs to elicit ras-independent responses central to
      neuronal differentiation, we analyzed voltage-dependent sodium (Na) channel
      expression in rat pheochromocytoma (PC12) cells after activation of a variety of
      endogenously and exogenously expressed RTKs. In PC12 cells expressing trkB (Ip et
      al., 1993), the increase in Na current density caused by brain-derived
      neurotrophic factor (BDNF) was similar to that observed upon activation of
      endogenous trkA by NGF. BDNF also increased type II Na channel mRNA expression,
      as did neurotrophin-3 in PC12 cells expressing trkC (Tsoulfas et al., 1993). In
      contrast, insulin did not increase type II Na channel mRNA expression or Na
      current density in PC12 cells, while epidermal growth factor (EGF) elicited
      small, yet reproducible increases in type II Na channel mRNA and Na current
      density when compared to NGF, even upon coexpression of an EGF receptor/p75
      receptor chimera (Yan et al., 1991). Finally, in PC12 cells expressing beta
      platelet-derived growth factor (PDGF) receptors (Heasley and Johnson, 1992), PDGF
      increased type II Na channel mRNA and Na current density to the same extent as
      NGF. The results show the capabilities of these RTKs in eliciting Na channel
      expression and the specificity arising due to differences in their intrinsic
      properties.

PMID- 7823131
TI  - Activation of a metabotropic glutamate receptor increases intracellular calcium
      concentrations in neurons of the avian cochlear nucleus.
AB  - Metabotropic glutamate receptors have been shown to stimulate
      phosphatidylinositol metabolism, and subsequently liberate Ca2+ from
      intracellular stores, in a variety of tissue and cell types. We previously
      demonstrated that glutamate could stimulate phosphatidylinositol metabolism,
      generating inositol-1,4,5-trisphosphate (IP3), in isolated cochlear nucleus
      tissue from the chick. Using the calcium indicator dye fura-2 and ratiometric
      fluorescent imaging, this study examined the ability of glutamate and its analogs
      to liberate Ca2+ from intracellular stores of neurons of the avian cochlear
      nucleus, and qualitatively characterized the pharmacological profile of such an
      action. In normal, Ca(2+)-containing medium, glutamate, kainate (KA), alpha-amino
      3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA), NMDA, quisqualate (QUIS), and
      (+/-)-aminocyclopentane-trans-dicarboxylate (ACPD) elicited increases in
      intracellular calcium concentrations ([Ca2+]i). In the absence of external Ca2+,
      glutamate, quisqualate, and ACPD evoked increases in [Ca2+]i. In normal medium,
      the ionotropic glutamate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione
      (CNQX) and the NMDA receptor antagonist 2-amino-5-phosphonovalerate (APV)
      attenuated but did not abolish the glutamate-evoked response and had no effect on
      the ACPD-evoked response. The putative metabotropic glutamate receptor antagonist
      2-amino-3-phosphonopropionate (AP3) was without effect on the glutamate- and ACPD
      evoked increases in [Ca2+]i in Ca(2+)-free medium. We conclude that a
      metabotropic glutamate receptor (mGluR) is present on cochlear nucleus neurons
      and is able to stimulate the phosphatidylinositol metabolism--Ca2+ signal
      transduction cascade.

PMID- 7823129
TI  - Specialized neuronal and glial contributions to development of the hamster
      lateral geniculate complex and circadian visual system.
AB  - The intergeniculate leaflet (IGL) is an integral part of the adult circadian
      visual system. It is characterized by the presence of retinal afferents and
      peptidergic cells projecting via a geniculohypothalamic tract (GHT) to the
      suprachiasmatic nucleus (SCN), site of the mammalian circadian clock. The adult
      IGL also contains abundant reactive astrocytes immunoreactive to GFAP. Because
      glia have a large role in brain development, we examined the ontogeny of the
      hamster IGL with respect to both glial and neuronal markers. Neuropeptide Y
      immunoreactive (NPY-IR) cells destined for the IGL appear on embryonic day 11
      (E11) in a matrix of vimentin (VIM)-IR radial glia. Migratory ellipsoid NPY-IR
      cells with long leading and trailing processes become oriented between the
      reticular thalamic neuroepithelial lobule, and the developing IGL. Most NPY-IR
      cells arrive in the IGL by E14 and extend axons ventrally into the GHT. These
      penetrate the SCN at P3 and arborize to an adult-like stage by P10. A specialized
      GFAP-IR radial glial path coinciding with the migratory route of NPY-IR cells
      appears by E14. As early as E15, cells contributing to this path are found
      displaced away from the ventricle. As the glial path disappears from the maturing
      brain, the entire length of the IGL becomes filled with GFAP-IR astrocytes. These
      features are consistent with translocation and transformation of a specialized
      set of radial glia into IGL astrocytes. The results demonstrate that the IGL is a
      large, developmentally important, feature of the lateral geniculate complex that
      is embryologically distinct from adjacent dorsal and ventrolateral geniculate
      nuclei.

PMID- 7823132
TI  - Transforming growth factor-beta 1 and forskolin modulate gap junctional
      communication and cellular phenotype of cultured Schwann cells.
AB  - Following peripheral nerve injury, Schwann cells undergo a series of cellular
      alterations that are thought to assist the regenerative process. Some of these
      changes are stimulated by the local release of cytokines and mitogenic factors.
      To test the hypothesis that cytokine regulation of gap junctional communication
      between cells helps to coordinate Schwann cell responses, cultured rat Schwann
      cells, from sciatic nerve, were utilized to study phasic changes induced by
      transforming growth factor-beta 1 (TGF beta 1), a cytokine released after nerve
      injury, or forskolin in combination with bovine pituitary extract (F-BPE), known
      for its mitogenic effects in vitro. In mitotically quiescent cultures, TGF beta 1
      significantly decreased both electrical and dye coupling mediated by gap
      junctions. Single-channel analysis revealed that cultured Schwann cells expressed
      gap junctions with two distinct channel sizes of about 26 pS and 44 pS. TGF beta
      1 treatment reduced coupling due to both populations of channels. Exposure to TGF
      beta 1 had a minimal effect on proliferation but significantly altered cellular
      morphology; cell bodies became flattened with multipolar processes within 72 hr.
      Additionally, immunolabeling for both low-affinity nerve growth factor receptor
      (L-NGFR) and glial fibrillary acidic protein (GFAP) were reduced, suggesting
      increased differentiation. In contrast, treatment with F-BPE significantly
      enhanced both electrical and dye coupling and stimulated Schwann cell
      proliferation. Additionally, cell bodies became more rounded with polarized,
      cytoplasmic processes contiguously aligned with adjacent cells. F-BPE reduced
      immunolabeling for L-NGFR but increased expression of both GFAP and the major
      peripheral myelin protein, P0. These data indicate that TGF beta 1 and/or F-BPE
      induce phenotypic changes in Schwann cells, including the coordinated regulation
      of proliferation and modulation of intercellular communication via gap junctions.
      Such mechanisms may underlie phasic responses that orchestrate recovery from
      nerve injury, indicating that Schwann cell gap junctions may be critical for
      peripheral nerve function.

PMID- 7823133
TI  - Expression and antibody inhibition of P-type calcium channels in human small-cell
      lung carcinoma cells.
AB  - P-type channels, a recently described form of voltage-gated calcium channels, are
      found in many central and peripheral neurons. In the present study, a partial
      cDNA clone sharing extensive nucleotide identity with a putative P-type voltage
      gated calcium channel alpha 1 subunit was isolated from a small-cell lung
      carcinoma (SCLC) cell line. Anti-peptide antibodies generated to a unique acidic
      stretch in the IVS5-S6 linker region of the putative SCLC P-type channel reacted
      specifically with a SCLC fusion protein produced in bacteria and with a cell
      surface molecule in SCLC cells. Calcium currents in SCLC cells, measured by whole
      cell patch clamp, were inhibited by these antibodies and by the P-type channel
      specific toxin omega-agatoxin IVA. The inhibitory effects of the antibody and the
      toxin were not additive, consistent with their proposed action on the same type
      of channel. These results provide evidence for the expression of P-type calcium
      channels by SCLC cells. The expression of neuron-related molecules by these cells
      is of particular interest because small-cell lung carcinoma is frequently
      associated with paraneoplastic disorders affecting the nervous system.

PMID- 7823134
TI  - Muscular production of individuated finger movements: the roles of extrinsic
      finger muscles.
AB  - Individuated finger movements--those in which one or more fingers are moved
      relatively independently of the movement or posture of other body parts--are
      produced in part by the action of the extrinsic finger muscles. Flexion/extension
      movements of the fingers are particularly dependent on these extrinsic muscles,
      most of which are multitendoned. How can contraction of multitendoned muscles
      move one digit without producing equivalent motion in other digits? This question
      was addressed by recording EMG activity from muscles of the forearm as trained
      rhesus monkeys performed flexion and extension individuated movements of each
      digit of the hand and of the wrist. Recordings showed that during movements of
      different fingers, a given muscle could act as an agonist, antagonist, or
      stabilizer of the digits it serves. Furthermore, during a given finger movement,
      several different muscles typically were active. A three-level connection model
      was developed that computed the relative motion of the digits during each finger
      movement based on the changes in EMG activity in the recorded muscles. The model
      showed that EMG activity changes in the extrinsic finger muscles, and the thenar
      muscles, could account for most of the motion of both the instructed digit and
      noninstructed digits. These results indicate that individuated finger movements
      were produced not by independent sets of muscles acting on each digit, but by the
      activity of several muscles, many of which act on more than one digit, combined
      such that the net effect was movement of one digit more than others.

PMID- 7823135
TI  - Forskolin and camptothecin induce a 30 kDa protein associated with melatonin
      production in Y79 human retinoblastoma cells.
AB  - The synthesis of melatonin in Xenopus retinas, chick and quail retinal cell
      cultures, and Y79 human retinoblastoma cells is stimulated by cAMP through a
      protein synthesis-dependent mechanism. In Y79 retinoblastoma cells, combined
      treatment with the RNA synthesis inhibitor camptothecin and agents that elevate
      cAMP, such as forskolin, causes a synergistic elevation of melatonin. Using two
      dimensional gel analysis we have identified a 30 kDa cytosolic protein (p30)
      whose radiolabeling was consistently increased in parallel with increases in
      arylalkylamine N-acetyltransferase activity and melatonin production that were
      induced by forskolin and/or camptothecin. Pulse-chase experiments suggest that
      the elevation in radiolabeling of p30 is due to increased synthesis. Three
      candidate proteins found in the mammalian pineal, protein 14-3-3, malate
      dehydrogenase, and recoverin, do not comigrate with p30.

PMID- 7823136
TI  - Sharp wave-associated high-frequency oscillation (200 Hz) in the intact
      hippocampus: network and intracellular mechanisms.
AB  - Sharp wave bursts, induced by a cooperative discharge of CA3 pyramidal cells, are
      the most synchronous physiological pattern in the hippocampus. In conjunction
      with sharp wave bursts, CA1 pyramidal cells display a high-frequency (200 Hz)
      network oscillation (ripple). In the present study extracellular field and unit
      activity was recorded simultaneously from 16 closely spaces sites in the awake
      rat and the intracellular activity of CA1 pyramidal cells during the network
      oscillation was studied under anesthesia. Current source density analysis of the
      high-frequency oscillation revealed circumscribed sinks and sources in the
      vicinity of the pyramidal layer. Single pyramidal cells discharged at a low
      frequency but were phase locked to the negative peak of the locally derived field
      oscillation. Approximately 10% of the simultaneously recorded pyramidal cells
      fired during a given oscillatory event. Putative interneurons increased their
      discharge rates during the field ripples severalfold and often maintained a 200
      Hz frequency during the oscillatory event. Under urethane and ketamine anesthesia
      the frequency of ripples was slower (100-120 Hz) than in the awake rat (180-200
      Hz). Halothane anesthesia prevented the occurrence of high-frequency field
      oscillations in the CA1 region. Both the amplitude (1-4 mV) and phase of the
      intracellular ripple, but not its frequency, were voltage dependent. The
      amplitude of intracellular ripple was smallest between -70 and -80 mV. The phase
      of intracellular oscillation relative to the extracellular ripple reversed when
      the membrane was hyperpolarized more than -80 mV. A histologically verified CA1
      basket cell increased its firing rate during the network oscillation and
      discharged at the frequency of the extracellular ripple. These findings indicate
      that the intracellularly recorded fast oscillatory rhythm is not solely dependent
      on membrane currents intrinsic to the CA1 pyramidal cells but it is a network
      driven phenomenon dependent upon the participation of inhibitory interneurons. We
      hypothesize that fast field oscillation (200 Hz) in the CA1 region reflects
      summed IPSPs in pyramidal cells as a result of high-frequency barrage of
      interneurons. The sharp wave associated synchronous discharge of pyramidal cells
      in the millisecond range can exert a powerful influence on retrohippocampal
      targets and may facilitate the transfer of transiently stored memory traces from
      the hippocampus to the entorhinal cortex.

PMID- 7823137
TI  - Calcium modulates the rapid kinetics of the odorant-induced cyclic AMP signal in
      rat olfactory cilia.
AB  - Although the cAMP and phosphoinositide (PI) second messenger systems are involved
      in olfactory signal transduction, aspects of their roles remain unclear. We have
      further examined the rapid kinetics of cAMP fluctuations in response to odorants
      in rat olfactory cilia isolated by calcium shock. Odorants cause a rapid and
      transient subsecond elevation of cAMP levels, as well as a more sustained signal
      lasting 5-10 sec. Basal cAMP levels demonstrate a biphasic calcium dependence;
      calcium enhanced both adenylyl cyclase (AC) and phosphodiesterase (PDE)
      activities. The odorant-induced cAMP response also demonstrated a biphasic
      dependence on calcium, with peak activity at 10 microM free calcium. All odorants
      tested were found to stimulate cAMP accumulation, and the dose-response curves
      were multiphasic, with less stimulation seen at higher concentrations. Dose
      response curves performed for isovaleric acid at two free calcium concentrations
      demonstrated that calcium can influence cellular responsiveness to odorants and
      may be involved with signal potentiation as well as desensitization.

PMID- 7823138
TI  - Characterization of voltage-activated currents in Hermissenda type B
      photoreceptors.
AB  - Two distinct voltage-dependent K+ currents have been previously identified in the
      type B-photoreceptors of Hermissenda: an early, rapidly inactivating K+ current
      (IA), and a late, 4-AP- and TEA-resistant voltage and Ca(2+)-dependent current
      (IK(Ca)). Using conventional two-electrode voltage-clamp techniques, we have
      characterized two additional currents, a late voltage-dependent outward K+
      current (IK(v)) and a voltage-dependent inward current identified as an inward
      rectifier (Iir). In addition, we have further studied the activation-inactivation
      kinetics of IA. In 0-Na+ ASW, Iir activates at a potential of > -50 mV, is
      steeply voltage-dependent and noninactivating, and reaches steady-state within
      800 msec to 3 sec at -100 mV. In addition to the variability in activation
      kinetics, there was also considerable variability in Iir magnitude (-5 to -80 nA,
      at -100 mV). Iir was blocked by external 4-AP (5 mM), external and internal TEA,
      internal Cs+, but not external Ba2+. The major component of outward K+ current in
      type B-photoreceptors is IK(v), the delayed rectifier. IK(v) was isolated after
      removal of IA and IK(Ca). IK(v) activates at around -25 mV or more positive
      membrane potentials and its activation and inactivation are strongly voltage
      dependent. IK(v) inactivation to steady state is reached within 1.5-2.5 sec. The
      wide range of activation-inactivation rates suggests that there may be kinetic
      subtypes of IK(v). The proposed "slow" IK(v) peaked in 50-90 msec at +30 mV, and
      decayed with a single exponential component with an average tau off of 279 msec.
      Proposed "intermediate" and "fast" IK(v) subtypes peaked within 12-50 msec at +30
      mV, and had a decay fitted by two exponentials, with an average tau 1 of 147 msec
      and tau 2 of 275 msec, respectively. IK(v) exhibited marked twin-pulse
      inactivation with a recovery time of 30-40 sec, and also exhibited time- and
      voltage-dependent cumulative inactivation to repeated depolarizing pulses. Both
      types of inactivation were quickly removed by a prepulse hyperpolarization. 4-AP
      (5 mM) produced partial to complete block of the inactivating component of IK(v),
      leaving only a residual sustained component. Complete block of the transient and
      sustained components of IK(v) was obtained by 100 mM TEA. Reliable voltage
      separation of IA from IK(v) was achieved by activating IA in the range of -50 to 
      20 mV, from a Vh of -80 mV. Voltage-dependent steady-state inactivation curves
      for IA were determined, yielding an average h0.5 value of -56 mV.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7823139
TI  - Novel classes of responsive and unresponsive C nociceptors in human skin.
AB  - One hundred ninety-four cutaneous C-fibers were recorded from the human peroneal
      nerve; 118 units were found by mechanical stimuli and 76 units were detected by
      electrical stimulation through a surface electrode. Needle electrodes were then
      inserted for electrical intradermal stimulation in the innervation territory of
      the units. Afferent and efferent sympathetic C-fibers were identified by slowing
      of conduction velocity after activation either by physical or chemical skin
      stimuli, or by arousal maneuvers eliciting sympathetic reflexes. In addition to
      mechano-heat-responsive C units (CMH) also found in previous studies, we here
      report on novel classes of C nociceptors in human skin, namely, units responding
      only to mechanical stimuli (CM), units responding only to heating (CH), and units
      that were insensitive to mechanical and heating stimuli and also to sympathetic
      provocation tests (CMiHi). With the electrical search technique we found 45% CMH,
      13% CM, 6% CH, 24% CMiHi, and 12% sympathetic units. Excitation by topically
      applied mustard oil occurred in 58% of CMH units, and in one-third of CM and
      CMiHi units, respectively. Some CM, CH, and CMiHi units were sensitized to
      heating and/or to mechanical stimuli after topical application of mustard oil or
      capsaicin. These units then acquired responsiveness to a stimulus modality to
      which they previously were insensitive. Such recruitment of previously silent
      nociceptors implies spatial summation to the nociceptive barrage at central
      levels, and may contribute both to primary hyperalgesia to heat and pressure
      after chemical irritation, and to secondary hyperalgesia as a consequence of
      central sensitization.

PMID- 7823140
TI  - Dopamine modulation of transient potassium current evokes phase shifts in a
      central pattern generator network.
AB  - Bath application of dopamine modifies the rhythmic motor pattern generated by the
      14 neuron pyloric network in the stomatogastric ganglion of the spiny lobster,
      Panulirus interruptus. Among other effects, dopamine excites many of the pyloric
      constrictor (PY) neurons to fire at high frequency and phase-advances the timing
      of their activity in the motor pattern. These responses arise in part from direct
      actions of dopamine to modulate the intrinsic electrophysiological properties of
      the PY cells, and can be studied in synaptically isolated neurons. The rate of
      rebound following a hyperpolarizing prestep and the spike frequency during a
      subsequent depolarization are both accelerated by dopamine. Based on theoretical
      simulations, Hartline (1979) suggested that the rate of postinhibitory rebound in
      stomatogastric neurons could vary with the amount of voltage-sensitive transient
      potassium current (IA). Consistent with this prediction, we found that dopamine
      evokes a net conductance decrease in synaptically isolated PY neurons. In voltage
      clamp, dopamine reduces IA, specifically by reducing the amplitude of the slowly
      inactivating component of the current and shifting its voltage activation curve
      in the depolarized direction. 4-Aminopyridine, a selective blocker of IA in
      stomatogastric neurons, mimics and occludes the effects of dopamine on isolated
      PY neurons. A conductance-based mathematical model of the PY neuron shows
      appropriate changes in activity upon quantitative modification of the IA
      parameters affected by dopamine. These results demonstrate that dopamine excites
      and phase-advances the PY neurons in the rhythmic pyloric motor pattern at least
      in part by reducing the transient K+ current, IA.

PMID- 7823141
TI  - Impairments on nonspatial self-ordered and externally ordered working memory
      tasks after lesions of the mid-dorsal part of the lateral frontal cortex in the
      monkey.
AB  - Monkeys with lesions of the mid-dorsal part of the lateral frontal cortex, which
      extends above the sulcus principalis as far as the midline (MDL lesions), were
      shown to exhibit severe and long-lasting impairments on certain nonspatial
      working memory tasks: the self-ordered and externally ordered tasks (experiments
      1, 2, 3, 5, 6, and 8). These tasks, which were modeled on similar ones previously
      used with patients, measure the capacity to monitor, within working memory, self
      generated choices and the occurrence of externally ordered stimuli. Monkeys with
      lesions of the adjacent posterior dorsolateral frontal cortex, which surrounds
      the arcuate sulcus (PA lesions), performed as well as the normal control animals
      on these tasks. Experiments 4 and 5 showed that the critical variable accounting
      for the impairment on the self-ordered and externally ordered working memory
      tasks by monkeys with MDL lesions is the size of the set of stimuli that must be
      monitored. Furthermore, the MDL lesions did not affect basic recognition memory
      (experiment 6), or primacy and recency mnemonic effects [i.e., the capacity to
      discriminate between the initial (or final) items and other items in a list of
      stimuli (experiments 4 and 7), or the capacity to select from a set of stimuli on
      the basis of a learned fixed sequence (experiment 9)]. Thus, lesions of the mid
      dorsal part of the lateral frontal cortex give rise to an impairment in working
      memory that depends on the size of the set of the stimuli that have to be
      monitored.

PMID- 7823142
TI  - Neonatal endotoxin exposure alters the development of the hypothalamic-pituitary
      adrenal axis: early illness and later responsivity to stress.
AB  - The long-term consequences of neonatal endotoxin exposure on hypothalamic
      pituitary-adrenal axis (HPA) function were assessed in adult female and male Long
      Evans rats. At 3 and 5 d of age, pups were administered endotoxin (Salmonella
      enteritidis, 0.05 mg/kg, i.p.) at a dose that provokes a rapid and sustained
      physiological response, but with no mortality. As adults, neonatally endotoxin
      treated animals exhibited significantly greater adrenocorticotrophic hormone
      (ACTH) and corticosterone responses to restraint stress than controls. In
      addition, dexamethasone pretreatment was less effective in suppressing ACTH
      responses to restraint stress in endotoxin-treated animals than in controls,
      suggesting decreased negative-feedback sensitivity to glucocorticoids. Neonatal
      endotoxin treatment elevated resting-state median eminence levels of
      corticotropin-releasing hormone (CRH) and arginine vasopressin in adult male
      animals, and arginine vasopressin in both adult males and females. Neonatal
      exposure to endotoxin also increased CRH mRNA expression in the paraventricular
      nucleus of the hypothalamus of adult males, with no difference in females.
      Finally, glucocorticoid receptor density was reduced across a wide range of brain
      regions in the neonatal endotoxin-treated, adult animals. These data illustrate
      the interactive nature of immune and endocrine systems during development. It
      appears that endotoxin exposure during critical stages of development decreases
      glucocorticoid negative-feedback inhibition of ACTH secretagogue synthesis, thus
      increasing HPA responsiveness to stress. The implication of these findings is
      that exposure to gram-negative LPS in early life can alter the development of
      neural systems which govern endocrine responses to stress and may thereby
      predispose individuals to stress-related pathology.

PMID- 7823143
TI  - Neuron-specific enolase: a neuronal survival factor in the retinal extracellular
      matrix?
AB  - To identify soluble proteins of the retinal interphotoreceptor matrix (IPM), we
      isolated IPM from the bovine eye by gentle lavage and subjected it to SDS-PAGE.
      In the resultant gel, a 46 kDa band was particularly prominent and appeared to be
      a single protein. This protein was electroblotted to nitrocellulose membrane,
      digested with trypsin, and selected peptides were isolated by HPLC and subjected
      to Edman microsequencing. The amino acid sequences of the peptides were found to
      be virtually identical to that of human neuron-specific enolase (NSE). A
      monoclonal antibody specific for human NSE confirmed the presence of this enzyme
      in the bovine IPM by both Western blotting and immunocytochemical analysis.
      Immunofluorescence microscopy demonstrated that NSE is mainly localized to the
      basal domain of the IPM surrounding photoreceptor cells but is also prominent in
      the inner segments of the cone photoreceptor neurons. When NSE was added to
      cultures of human retinoblastoma cells, no effect on morphology was observed.
      However, a positive effect on cell growth and/or survival was readily apparent.
      It thus seems that not only is NSE a significant component of the retinal
      extracellular matrix, but that it could function as a survival (neuronotrophic)
      factor for photoreceptor neurons.

PMID- 7823144
TI  - Developmental and growth factor-induced regulation of nestin in oligodendrocyte
      lineage cells.
AB  - The expression and regulation of nestin, an intermediate filament protein
      associated with neuroepithelium-derived progenitor cells, was studied in
      developing oligodendrocytes. We analyzed glial cells cultured from late embryonic
      rat cerebral cortex, tissue prints from neonatal rat brains, and the
      oligodendrocyte cell line CG-4. Using cortical- or CG-4-derived oligodendrocyte
      lineage cells, Northern blot analysis demonstrated that nestin mRNA was highly
      expressed in proliferating O-2A progenitors, but downregulated in differentiated
      oligodendrocytes. Immunocytochemistry of cultured cells and tissue prints
      demonstrated that pre-O-2A cells and O-2A progenitors expressed high levels of
      the nestin protein. In contrast, nestin expression decreased during the pro
      oligodendroblast stage, and the majority of oligodendrocytes were not labeled
      with anti-nestin antibodies. Culture conditions (PDGF+bFGF or B104-conditioned
      medium) that maintained O-2A progenitor proliferation and prevented
      differentiation enhanced expression of nestin mRNA transcripts and protein. In
      comparison, analysis of cortical astrocyte cultures demonstrated that type 1
      astrocytes, but not type 2, expressed nestin mRNA and protein. Our findings
      demonstrate that nestin is expressed in developing glial cells, which is
      suggestive that this intermediate filament protein may play an important role
      during gliogenesis.

PMID- 7823145
TI  - Monopolar cell axons in the first optic neuropil of the housefly, Musca domestica
      L., undergo daily fluctuations in diameter that have a circadian basis.
AB  - Two types of monopolar cell interneurons, each with a single representative in
      every unit cartridge of the first optic neuropil, or lamina, of the housefly's
      optic lobe, have axons that undergo cyclical changes in diameter. The axons are
      largest during the beginning of day in a normal LD light cycle and smallest
      during the middle of the night, changes that were however significant only for
      one of the cells (L2). The axon cross-sectional area and its cyclical change for
      both L1 and L2 were both larger in the proximal lamina. The changes are not a
      simple consequence of relative osmotic change. Dehydration paradoxically
      increases axon size, and also fails to alter the day/night rhythm of axon size
      changes. Under conditions of constant darkness, both axons decrease in size, and
      one of the cells (L2) retains its cyclical size changes, being larger in the
      subjective day than in the subjective night. Under conditions of constant light,
      both axons increase in size, and L2 again shows a cyclical size change, just as
      under conditions of constant darkness. These changes seen under constant
      conditions are, by definition, circadian in origin. The effects of exposure to
      light or darkness can partially reset these circadian changes. One extra hour of
      light during the day increases the size of L1 and L2, whereas 1 hr of extra dark
      during the night does not decrease their size. It takes 13 hr of light to reverse
      the rhythm in size. The mechanism for all these changes is unclear but may
      involve ionic fluxes, possibly that are secondary to osmotic shifts and probably
      that involve at least two independent processes.

PMID- 7823146
TI  - Transforming growth factor-beta blocks myelination but not ensheathment of axons
      by Schwann cells in vitro.
AB  - Mechanisms regulating Schwann cell differentiation into a myelinating or a mature
      nonmyelinating phenotype during development are poorly understood. Humoral
      factors such as members of the transforming growth factor-beta (TGF-beta) family,
      which are found in the developing and adult mammalian nervous system and are
      known to affect cell differentiation, could be involved. We tested the effects of
      TGF-beta isoforms on the ensheathment and myelination of dorsal root ganglion
      (DRG) neurons by Schwann cells in vitro. Rat embryonic DRG neurons and Schwann
      cells from the sciatic nerve were isolated, purified, and recombined. In serum
      free conditions, TGF-beta blocked both Schwann cell myelination and the
      expression of the myelin-related molecules galactocerebroside, P0, myelin
      associated glycoprotein, and myelin basic protein. In contrast, the expression of
      molecules characteristic of mature nonmyelinating Schwann cells, including neural
      cell adhesion molecule, L1, and nerve growth factor receptor, was maintained when
      compared to Schwann cells in nondifferentiated cultures. Notably, the expression
      of glial fibrillary acidic protein, which is expressed only in mature
      nonmyelinating Schwann cells in vivo, was increased 10-fold in our cultures by
      TGF-beta. Electron microscopic analysis indicated that in the presence of TGF
      beta, basal lamina deposition by Schwann cells was slightly increased. Most
      importantly, many axons in TGF-beta-treated cultures received ensheathment
      typical of mature nonmyelinated nerves. These effects of TGF-beta were partially
      reversed by specific neutralizing anti-TGF-beta antibodies. We interpret these
      results as evidence that TGF-beta regulates Schwann cell differentiation in vitro
      by blocking the expression of the myelinating phenotype and promoting the
      development of the nonmyelinating phenotype.

PMID- 7823147
TI  - Dynamics of protein phosphorylation in sensory neurons of Aplysia.
AB  - Protein phosphorylation plays important roles in the mechanisms underlying
      serotonin (5-HT)-induced presynaptic facilitation of Aplysia sensory neurons. To
      study mechanisms involved in facilitation, we investigated the pattern of protein
      phosphorylation in sensory neurons as a function of different durations of 5-HT.
      Two minutes and 1.5 hr treatments with 5-HT altered the phosphorylation of 5 and
      10 proteins, respectively. These different duration treatments with 5-HT produced
      unique effects on the phosphorylation of different sets of proteins. This result
      suggests that cells may encode and measure the duration of a stimulus by the
      pattern of specific proteins that are phosphorylated or dephosphorylated. In
      addition, because the changes in phosphorylation produced by 2 min treatments
      with 5-HT were not observed after 25 min treatments with 5-HT, mechanisms must
      exist for the transient phosphorylation of some proteins even when the 5-HT
      treatment persists. Anisomycin, an inhibitor of protein synthesis, blocked the
      effect of 1.5 hr treatments with 5-HT on the phosphorylation of six proteins but
      had no effect on the phosphorylation change of four other proteins. Both CPT-cAMP
      (an activator of protein kinase A) and PDAc (an activator of protein kinase C)
      mimicked the effects of 5-HT on four proteins. Interestingly, the effect of 5-HT
      on these four proteins did not require protein synthesis. CPT-cAMP, but not PDAc,
      mimicked the effect of 5-HT on one protein (L55) and, the effect of 5-HT on this
      protein appeared to require protein synthesis. Because both activation of PKA and
      protein synthesis are involved in the induction of long-term facilitation,
      protein L55 is a good candidate for a protein that might play a key role in long
      term facilitation. Finally, the effects of 5-HT on four proteins were not
      mimicked by either CPT-cAMP or PDAc. This finding raises the interesting
      possibility that some effects of 5-HT are mediated by second-messenger systems
      other than PKA or PKC.

PMID- 7823148
TI  - Retrograde transport of plasticity signals in Aplysia sensory neurons following
      axonal injury.
AB  - Following injury to their peripheral branches, mechanosensory neurons in Aplysia
      display long-term plasticity that is expressed as soma hyperexcitability,
      synaptic facilitation, and neurite outgrowth. To investigate the nature of
      signals that convey information about distant axonal injury, we have investigated
      the development of injury-induced soma hyperexcitability in two in vitro
      preparations. In isolated ganglia, proximal nerve crush caused hyperexcitability
      to appear sooner than did distal crush, and the difference in development of
      hyperexcitability indicated that the injury signal moved at a rate (36 mm/d)
      similar to previously reported rates of retrograde axonal transport in this
      animal. This hyperexcitability was not due to interruption of continuous
      retrograde transport of trophic substances (a negative signal) because inhibitors
      of axonal transport applied to uncrushed nerve segments did not induce
      hyperexcitability. Indeed, inhibitors of axonal transport blocked crush-induced
      hyperexcitability, indicating that positive injury signals are involved. Crush
      induced hyperexcitability was unaffected by bathing the nerve in tetrodotoxin or
      the ganglion in Cd2+, suggesting that the retrograde signals depend upon neither
      spike activity in the nerve nor synaptic transmission in the ganglion. Close
      excision of sensory neuron somata (which largely eliminated delays attributable
      to axonal transport) produced soma hyperexcitability that was expressed after 10
      hr and lasted at least 17 d. These data indicate that axonal injury mobilizes
      signal molecules that are conveyed by retrograde axonal transport into the soma
      and possibly the nucleus, where they induce long-term plasticity similar to that
      expressed by these cells during learning and memory.

PMID- 7823149
TI  - Inhibition of voltage-gated K+ channel gene expression by the neuropeptide
      thyrotropin-releasing hormone.
AB  - Many neurotransmitters regulate action potential activity in neuronal, endocrine,
      and cardiac cells by rapidly modulating the gating of K+ channels.
      Neurotransmitters might also produce prolonged effects on excitability by
      regulating the expression of K+ channel genes. Here we show that the neuropeptide
      thyrotropin-releasing hormone (TRH) down-regulates Kv1.5 and Kv2.1 K+ channel
      mRNAs in clonal pituitary cells. The effect on Kv1.5 mRNA expression does not
      require protein synthesis and is due to decreased transcription. Immunoblots
      demonstrate that Kv1.5 and Kv2.1 immunoreactivities are significantly reduced by
      TRH within 12 hr. The change in channel protein expression is associated with a
      decrease in voltage-gated K+ currents. Thus, TRH enhances excitability by
      inhibiting K+ channel gene expression. Neuropeptide regulation of K+ channel gene
      expression may produce long-term changes in neuronal action potential activity
      and synaptic transmission.

PMID- 7823150
TI  - Muscarinic receptors modulate N-, P-, and L-type Ca2+ currents in rat striatal
      neurons through parallel pathways.
AB  - Muscarinic modulation of calcium currents was studied in acutely isolated
      striatal neurons from the adult rat using the whole-cell configuration of the
      patch-clamp technique. Muscarinic agonists reduced calcium currents through two
      distinct signaling pathways. One pathway depended upon PTX-sensitive G-proteins
      and targeted N- and P-type currents. The other pathway depended upon PTX
      insensitive G-proteins and was rendered inactive by high intracellular
      concentrations of BAPTA and targeted L-type currents. The modulation of N- and P
      type currents was relieved by strong depolarizing prepulses, whereas the
      modulation of L-type currents was not. These findings support the proposition
      that parallel signaling pathways exist between muscarinic receptors and calcium
      channels.

PMID- 7823151
TI  - Gamma (40-100 Hz) oscillation in the hippocampus of the behaving rat.
AB  - The cellular generation and spatial distribution of gamma frequency (40-100 Hz)
      activity was examined in the hippocampus of the awake rat. Field potentials and
      unit activity were recorded by multiple site silicon probes (5- and 16-site
      shanks) and wire electrode arrays. Gamma waves were highly coherent along the
      long axis of the dentate hilus, but average coherence decreased rapidly in the
      CA3 and CA1 directions. Analysis of short epochs revealed large fluctuations in
      coherence values between the dentate and CA1 gamma waves. Current source density
      analysis revealed large sinks and sources in the dentate gyrus with spatial
      distribution similar to the dipoles evoked by stimulation of the perforant path.
      The frequency changes of gamma and theta waves positively correlated (40-100 Hz
      and 5-10 Hz, respectively). Putative interneurons in the dentate gyrus discharged
      at gamma frequency and were phase-locked to the ascending part of the gamma waves
      recorded from the hilus. Following bilateral lesion of the entorhinal cortex the
      power and frequency of hilar gamma activity significantly decreased or
      disappeared. Instead, a large amplitude but slower gamma pattern (25-50 Hz)
      emerged in the CA3-CA1 network. We suggest that gamma oscillation emerges from an
      interaction between intrinsic oscillatory properties of interneurons and the
      network properties of the dentate gyrus. We also hypothesize that under
      physiological conditions the hilar gamma oscillation may be entrained by the
      entorhinal rhythm and that gamma oscillation in the CA3-CA1 circuitry is
      suppressed by either the hilar region or the entorhinal cortex.

PMID- 7823152
TI  - Enduring effects of chronic corticosterone treatment on spatial learning,
      synaptic plasticity, and hippocampal neuropathology in young and mid-aged rats.
AB  - Prolonged treatment with stress levels of corticosterone has been reported to
      produce changes in the hippocampus. In the experiments reported here, we examined
      for functional and morphological consequences of this treatment. First, young
      adult or mid-aged male Long-Evans rats were treated for either 1 or 3 months with
      corticosterone, at a dose sufficient to mimic the elevated hormone levels
      observed following exposure to mild stress. Two weeks following the termination
      of treatment, the animals were tested in the Morris water maze to assess spatial
      learning. No behavioral deficits were observed after 1 month of treatment. A 3
      month treatment period also had no effect in young rats, but produced a learning
      impairment in the mid-aged rats. We then examined whether the effect of elevated
      corticosterone in mid-aged animals could be produced by a physiological stressor.
      Mid-aged rats were maintained for 6 months under conditions of low or high social
      stress. Six months of exposure to high social stress produced significant spatial
      learning impairments in the Morris water maze. These effects were absent in high
      social stress animals that had been previously adrenalectomized (with low-level
      corticosterone replacement), suggesting that elevated glucocorticoid levels
      mediate the effects of stress on spatial memory in older animals. In a final
      experiment, mid-aged rats were treated with corticosterone at levels that
      mimicked those naturally occurring at the diurnal peak (medium-B: 12-17
      micrograms/dl) or in response to stress (high-B: 25-32 micrograms/dl). Only rats
      exposed to high levels of corticosterone demonstrated impaired performance in the
      Morris water maze.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7823153
TI  - Head direction cells recorded in the anterior thalamic nuclei of freely moving
      rats.
AB  - Previous studies have identified neurons in the postsubiculum which discharge as
      a function of the animal's head direction in the horizontal plane, independent of
      its behavior and location in the environment. Anatomical studies have shown that
      the postsubiculum contains reciprocal connections with the anterior thalamic
      nuclei (ATN). In order to determine how the head direction (HD) cell signal is
      processed in the brain, single-unit recordings were monitored in the ATN of
      freely moving rats in order to characterize their behavioral and spatial
      correlates. Animals were trained to retrieve food pellets thrown randomly into a
      cylindrical apparatus containing a single orientation cue. Single unit recordings
      in the ATN showed that approximately 60% of the recorded cells discharged in
      relation to the animal's head direction in the horizontal plane. Observation of
      the animal and quantitative analyses showed that HD cell firing was not dependent
      on the animal's behavior, trunk position, linear speed, angular head velocity, or
      location in the environment. Most of these cells were localized to the anterior
      dorsal thalamic nucleus. Each HD cell contained only one head direction at which
      the cell discharged maximally and the firing rate decreased linearly away from
      this preferred direction. The preferred firing directions from all cells recorded
      were distributed over a 360 degrees range. Quantitative analysis showed that
      these cells contained similar discharge parameters (peak firing rate, directional
      firing range) to values reported previously for postsubicular HD cells (Taube et
      al., 1990a). Experiments involving rotation of the orientation cue showed that
      the preferred firing direction could be controlled by a salient visual cue. In
      contrast to postsubicular HD cells, passive rotation of a restrained animal
      showed that most ATN HD cells ceased discharging when the animal's head was
      oriented in the preferred direction. These findings demonstrate the presence of
      HD cells in the ATN and indicate the potential importance of this area for
      spatial navigation. The origin of the head direction signal is discussed and it
      is concluded that because of the presence of reciprocal connections between the
      postsubiculum and the ATN, further studies are required in order to determine the
      direction in which this head-directional information is flowing. Finally, ATN HD
      cells differ from postsubicular HD cells by appearing to require volitional
      motoric input.

PMID- 7823154
TI  - Inhibition of long-term potentiation in the dentate gyrus of freely moving rats
      by the metabotropic glutamate receptor antagonist MCPG.
AB  - Metabotropic glutamate receptors (mGluRs) are critically involved in the
      maintenance of long-term potentiation (LTP) (Reymann and Matthies, 1989; Behnisch
      et al., 1991; Izumi et al., 1991; Bashir et al., 1993). In order to assess
      further the physiological role of MGluRs in LTP, we injected freely moving rats
      with the recently available, competitive mGluR antagonist (R,S)-alpha-methyl-4
      carboxyphenylglycine (MCPG) intraventricularly and recorded extracellularly the
      population spike (PS) as well as the field excitatory postsynaptic potential
      (fEPSP) of the granule cells of the dentate gyrus in response to stimulation of
      fibers of the perforant path. MCPG was administered in two concentrations (A = 20
      mM/5 microliters; B = 200 mM/5 microliters) either 30 min prior to or 5 min after
      LTP induction. Sodium chloride infusion served as a control. Normal synaptic
      transmission was not altered by MCPG. However, the mGluR antagonist inhibited LTP
      in a concentration-dependent manner. Concentration A did not influence the
      potentiation shortly after the tetanus. In the PS, short-term potentiation (STP),
      which is decremental in its time course, occurred normally, but in contrast to
      controls the potentiation declined back to baseline values after 2-3 hr. This
      dose also reduced the posttetanic increase in the slope function of the fEPSP,
      and led to a time course of potentiation similar to that for the PS.
      Concentration B completely abolished the tetanus-induced potentiation. This block
      was similar to that obtained for the NMDA antagonist 2-amino-5
      phosphonopentanoate (AP5). Both MCPG concentrations had no influence on the time
      course of preestablished LTP. These effects seem to be due to the action of the
      (+)-isomer of MCPG, since intracerebroventricular application of the (-)-isomer
      was without effect on the duration and magnitude of LTP. In addition, we were
      interested in the mGluR subtypes involved in the blocking mechanism of MCPG.
      1S,3R-aminocyclopentane-1,3-dicarboxic acid (ACPD)-activated PPI hydrolysis in
      hippocampal slices was competitively inhibited by MCPG at a concentration of 1 mM
      or higher. In contrast, this concentration of MCPG did not affect the reduction
      of forskolin-stimulated cAMP formation by ACPD. These results corroborate recent
      findings that mGluRs are required for the induction of LTP in CA1 and CA3 in
      vitro (Bashir et al., 1993; Sergueeva et al., 1993) and in vivo (Riedel and
      Reymann, 1993). The process of STP is found to be independent of mGluR
      activation.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7823155
TI  - CNS myelin and oligodendrocytes of the Xenopus spinal cord--but not optic nerve-
      are nonpermissive for axon growth.
AB  - In vitro assays reveal that myelin and oligodendrocytes of the Xenopus spinal
      cord (SC) are--unlike corresponding components of the optic nerve/tectum (OT)-
      nonpermissive substrates for regenerating retinal axons. The number of growth
      cones that crossed SC oligodendrocytes is low but increases significantly (four-
      to fivefold) in the presence of the antibody IN-1, in which case their numbers
      are similar to the number of growth cones (approximately 60%) that cross OT
      oligodendrocytes with or without IN-1. IN-1 neutralizes neurite growth inhibitors
      (NI) of rat CNS myelin, indicating that mammalian-like NI are associated with
      Xenopus SC myelin and oligodendrocytes but not with the OT. IN-1
      immunocytochemistry on sections supports this view: SC myelin was stained with IN
      1, whereas OT myelin and PNS myelin were not.

PMID- 7823156
TI  - Human trks: molecular cloning, tissue distribution, and expression of
      extracellular domain immunoadhesins.
AB  - Using molecular cloning techniques, human homologs of the known members of the
      trk family of neurotrophin receptors have been cloned and sequenced. Overall,
      there is a high degree of similarity between the human sequences and those from
      other mammals; however, there are differences in splicing patterns. There are two
      spliced forms of the extracellular domain of trkC in the human, a finding that
      has not been described in other species. In contrast, fewer spliced forms were
      detected of the intracellular domains of human trkB and trkC than has been
      described in other mammals. Northern analysis and in situ hybridization
      experiments indicate that the human trks are expressed in a similar pattern to
      that described in other mammals. Expression of the trk extracellular domains as
      fusion proteins with IgG heavy chain yields soluble molecules that mimic intact
      trks in their binding specificity and affinity. These soluble chimeras block the
      biological activity of their cognate neurotrophin(s) in vitro.

PMID- 7823157
TI  - Clustering of Na+ channels and node of Ranvier formation in remyelinating axons.
AB  - Polyclonal antibodies were raised against a well conserved region of the
      vertebrate Na+ channel and were affinity purified for use in immunocytochemistry.
      Focal demyelination of rat sciatic axons was initiated by an intraneural
      injection of lysolecithin and Na+ channel clustering was followed at several
      stages of myelin removal and repair. At 1 week post-injection axons contained
      long, fully demyelinated regions. Na+ channel clusters appeared only at heminodes
      forming the borders of these zones, and at widely spaced isolated sites that may
      represent former nodes of Ranvier. Over the next few days proliferating Schwann
      cells adhered to axons and began to extend processes. Clusters of Na+ channels
      appeared at the edges of these structures. As the Schwann cells elongated, the
      clusters seemed to move with them, since they remained at edges and the distance
      between aggregates increased. Clusters associated with different Schwann cells
      ultimately approached each other and appeared to fuse. Na+ channels then
      coalesced further at these sites, forming new nodes of Ranvier in regions that
      previously were internodal. If Schwann cell proliferation were blocked by
      mitomycin, no new clusters of Na+ channels appeared within internodes. Under
      these conditions, heminodal clusters remained visible at 1 week postinjection,
      but by 2 weeks they were no longer detectable, suggesting that proliferating
      Schwann cells are required for their maintenance. Clusters at normal nodes of
      Ranvier remained. It is concluded that Na+ channel aggregation and mobility in
      demyelinated nerve fibers is controlled by adhering Schwann cells, resulting in
      the formation of stable new nodes of Ranvier during remyelination.

PMID- 7823158
TI  - Pharmacologically distinct, pertussis toxin-resistant inward currents evoked by
      metabotropic glutamate receptor (mGluR) agonists in dorsolateral septal nucleus
      (DLSN) neurons.
AB  - We have reported previously that a selective metabotropic glutamate receptor
      (mGluR) agonist, (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD),
      caused a slow membrane depolarization in rat dorsolateral septal nucleus (DLSN)
      neurons. Using single electrode voltage-clamp recording methods, we now
      investigate the pharmacological properties of the receptor that mediates ACPD
      induced membrane currents in DLSN neurons recorded from pertussis toxin (PTX)
      treated rats. Two pharmacologically distinct inward currents, that is, the ACPD
      current and Qm current, have been identified based on their agonist preference
      and sensitivity to various antagonists. The ACPD current is blocked by L-2-amino
      4-phosphonobutyric acid (L-AP4), but is insensitive to L-aspartic acid-beta
      hydroxamate (L-AA beta H), (+)-alpha-methyl-4-carboxyphenylglycine (+)-MCPG), or
      L-2-amino-3-phosphonopropionic acid (L-AP3). The Qm current is blocked by L-AA
      beta H and (+)-MCPG, but is insensitive to L-AP3 or L-AP4. These two inward
      currents distribute differentially within subpopulations of DLSN neurons. The
      ACPD current is the only current observed in most DLSN "burster" neurons, while
      the Qm current is observed more frequently in DLSN "nonburster" neurons. The
      pharmacological profiles of these currents suggest that the Qm current is likely
      mediated by mGluR1 or mGluR5, while the ACPD current is mediated by receptors
      that are pharmacologically distinct from any of the currently cloned mGluRs.

PMID- 7823159
TI  - Overexpression of synaptophysin enhances neurotransmitter secretion at Xenopus
      neuromuscular synapses.
AB  - Previous studies have suggested the importance of synaptophysin (p38), a major
      integral membrane protein of the synaptic vesicle, in transmitter secretion, but
      few have directly addressed its functional role at intact synapses. In the
      present study, injection of synthetic mRNA for synaptophysin into one of the
      early blastomeres of a Xenopus embryo resulted in elevated synaptophysin
      expression in 1 and 2 d embryos and in cultured spinal neurons derived from the
      injected blastomere, as shown by immunocytochemistry. At neuromuscular synapses
      made by neurons overexpressing synaptophysin [p38(+)] in 1 d cell cultures, the
      spontaneous synaptic currents (SSCs) showed a markedly higher frequency, as
      compared to control synapses. This increase in frequency was not accompanied by a
      change in the mean amplitude or the amplitude distribution of the SSCs,
      suggesting that synaptophysin is not involved in determining the size of
      transmitter quanta. The impulse-evoked synaptic currents (ESCs) of synapses made
      by p38(+) neurons showed increased amplitude as well as reduced fluctuation and
      delay of onset of ESCs. Under high-frequency tetanic stimulation at 5 Hz, the
      rate of tetanus-induced depression was faster for p38(+) neurons. Taken together,
      these results suggest a role for synaptophysin in the late steps of transmitter
      secretion, affecting the probability of vesicular exocytosis and/or the number of
      synaptic vesicles initially docked at the active zone.

PMID- 7823160
TI  - Calcitonin gene-related peptide: possible role in formation and maintenance of
      neuromuscular junctions.
AB  - The expression and content of calcitonin gene-related peptide (CGRP) and
      secretogranin II (SgII) in adult rat motor neurons were examined by in situ
      hybridization, Northern blot analysis, and immunocytochemistry. Normal motor
      nerve terminals did not contain detectable CGRP or SgII. Ten to 15 days after a
      peripheral nerve crush about 80% of the motor nerve terminals reinnervating the
      soleus (SOL) muscle contained detectable CGRP but no SgII. Thereafter, the
      percentage of CGRP-positive terminals declined towards zero. In the spinal cord,
      CGRP expression was higher than normal 1 d after a sciatic nerve crush and
      increased during the next few days. No increase in SgII expression was observed.
      Nerve blocks by tetrodotoxin (TTX) and botulinum toxin (BoTX) increased CGRP
      content and expression in motor neurons but had no effect on SgII. After 10 d of
      BoTX treatment and 33 d of TTX treatment (the longest time points studied), more
      than 90% of the motor nerve terminals stained for CGRP. The density of large
      dense core vesicles (LDCVs) was also higher than normal in such terminals. Some
      increase in CGRP content and expression occurred in the nontreated side. In a
      group of rats, the peroneal nerve was stimulated electrically with brief,
      intermittent pulse trains at 100 Hz. The stimulation was applied below a TTX
      block that had started 7 or 19 d earlier. One minute of such stimulation was
      sufficient to remove CGRP from most of the terminals.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7823161
TI  - Diazepam, given postischemia, protects selectively vulnerable neurons in the rat
      hippocampus and striatum.
AB  - Following cerebral ischemia, certain populations of neurons degenerate. Excessive
      accumulation of excitatory amino acids in the synaptic cleft, activation of
      excitatory amino acid receptors, and influx of calcium into neurons play a key
      role in the development of ischemia-induced neuronal death. We hypothesized that
      neuroprotection may be achieved by enhancing inhibitory (i.e., gamma-aminobutyric
      acid, GABA) neurotransmission to offset excitation. Diazepam, a drug that
      increases GABA-induced chloride channel opening, was administered (10 mg/kg,
      i.p.) to rats 1 and 2 hr following 15 min of transient global ischemia, when
      hippocampal GABA levels, increased during ischemia, returned to basal. Rats were
      maintained normothermic during ischemia and became hypothermic following the
      injections of diazepam. Four days later, rats were sacrificed and the brains were
      examined for neuronal degeneration and the presence of GABAA receptors labeled by
      35S-t-butylbicyclophosphorothionate (35S-TBPS). There was substantial
      neuroprotection of striatal neurons and pyramidal neurons in the CA1 area of the
      hippocampus. In addition, diazepam prevented the loss of 35S-TBPS binding sites
      in the striatum and in the dendritic fields of the CA1 hippocampus following
      ischemia. Since hypothermia, itself, is neuroprotective, we determined if
      hypothermia was required for the ability of diazepam to produce neuroprotection.
      Diazepam was microinjected into the CA1 hippocampus 1 and 2 hr following
      ischemia, and rats remained normothermic. Four days later, diazepam still
      produced substantial protection of hippocampal neurons. Thus, postischemic
      hypothermia may have contributed to the neuroprotection by diazepam when it was
      administered systemically, but the neuroprotective effect of diazepam did not
      require hypothermia. We conclude that delayed enhancement of GABAergic
      neurotransmission directly at the site of vulnerability following an ischemic
      event protects the vulnerable neurons from death.

PMID- 7823162
TI  - Maintenance and degradation of proteins in intact and severed axons: implications
      for the mechanisms of long-term survival of anucleate crayfish axons.
AB  - Protein maintenance and degradation are examined in the severed distal
      (anucleate) portions of crayfish medial giant axons (MGAs), which remain viable
      for over 7 months following axotomy. On polyacrylamide gels, the silver-stained
      protein banding pattern of anucleate MGAs severed from their cell bodies for up
      to 4 months remains remarkably similar to that of intact MGAs. At 7 months
      postseverance, some (but not all) proteins are decreased in anucleate MGAs
      compared to intact MGAs. To determine the half-life of axonally transported
      proteins, we radiolabeled MGA cell bodies and monitored the degradation of newly
      synthesized transported proteins. Assuming exponential decay, proteins in the
      fast component of axonal transport have an average half-life of 14 d in anucleate
      MGAs and proteins in the slow component have an average half-life of 17 d. Such
      half-lives are very unlikely to account for the ability of anucleate MGAs to
      survive for over 7 months after axotomy.

PMID- 7823163
TI  - Topological precision in the thalamic projection to neonatal mouse barrel cortex.
AB  - Somatosensory thalamus and cortex in rodents contain topological representations
      of the facial whisker pad. The thalamic representation of a single whisker
      ("barreloid") is presumed to project exclusively to the cortical representation
      ("barrel") of the same whisker; however, it was not known when this
      correspondence is established during early development, nor how precise the
      thalamocortical projection is at birth, before formation of barrels and
      barreloids. To answer these questions, we retrogradely labeled thalamocortical
      projection neurons in fixed brain slices from 0-8 d old (P0-P8) mice, by placing
      paired deposits of two fluorescent dyes in adjacent barrels or (before barrel
      formation) in adjacent loci in upper cortical layers. At all ages studied, a
      negligible fraction of the retrogradely labeled cells was double labeled,
      implying that branches of single thalamocortical axons never extended within
      layer IV over an area wider than a single barrel. In P0 preparations, 70% of
      paired dye deposits placed 75-200 microns apart resulted in statistically
      significant segregation of labeled cell clusters in the thalamus. Quantitative
      analysis indicated that on P0 about 70% of thalamocortical axons were within 1.3
      presumptive barrel diameters from their topologically precise target. In P4-P8
      preparations, the great majority of thalamic cells retrogradely labeled from a
      single barrel were found in a single barreloid, implying a 1:1 projection of
      barreloids to barrels. The postnatal increase in topological precision was
      reproduced by a computer simulation, which assumed that many aberrant axons
      corrected their initial targeting error by extending terminal arborizations
      asymmetrically, towards the center of their appropriate barrel.

PMID- 7823164
TI  - CD9, a major platelet cell surface glycoprotein, is a ROCA antigen and is
      expressed in the nervous system.
AB  - We previously generated a monoclonal antibody (mAb), ROCA1, which binds
      preferentially to rostral versus caudal sympathetic ganglia and intercostal
      nerves. Two other mAbs, ROCA2 and B2C11, bind to the same structures but not in
      rostrocaudal gradients. All three mAbs recognize a 26 kDa cell surface protein.
      Amino acid sequence data obtained from the affinity purified 26 kDa protein
      showed some homology with human CD9, a tetraspan protein implicated in
      intercellular signaling in hematopoietic cells. Using the PCR, we obtained cDNA
      clones representing the entire rat CD9 coding sequence from sciatic nerve and
      sympathetic ganglia. ROCA1, ROCA2, and B2C11 each immunoprecipitate a 26 kDa
      protein from CHO cells stably transfected with one of the clones, demonstrating
      that the ROCA cell surface antigen is indeed rat CD9. We find that CD9 mRNA is
      widely expressed, with particularly high levels present in a number of neural
      tissues. In situ hybridization demonstrates that peripheral neurons and Schwann
      cells, as well as adrenal chromaffin cells express CD9 mRNA. Consistent with
      immunoblot analyses showing that, unlike the ROCA1 epitope, the 26 kDa protein is
      not expressed in a rostrocaudal gradient, we find similar levels of rat CD9 mRNA
      in rostral and caudal intercostal nerves. In developing postnatal rat sciatic
      nerve, CD9 mRNA levels are coordinately regulated with the expression of myelin
      genes. These results provide another example of a cell surface protein expressed
      by both hematopoietic and neural cells, and suggest a role for CD9 in
      intercellular signaling in the nervous system.

PMID- 7823165
TI  - An anti-CD9 monoclonal antibody promotes adhesion and induces proliferation of
      Schwann cells in vitro.
AB  - We have recently found that CD9, a cell surface glycoprotein involved in
      intercellular signaling in hematopoietic cells, is also expressed by neurons and
      glia in the peripheral nervous system. Antibody perturbation experiments were
      conducted to examine the function of CD9 in neural cells. Three anti-CD9
      monoclonal antibodies (mAbs) (ROCA1, ROCA2, B2C11) were tested for their ability
      to promote adhesion of several Schwann cell lines (S-16, RN22, JS1), primary
      Schwann cells and PC12 cells. Only B2C11 promotes adhesion in all cells tested.
      Although ROCA2 immunolabels living cells strongly, it had no effect on the
      adhesion of any of these cells. In addition, ROCA1 and several positive-staining,
      control mAbs also had no effect. Another mAb, 192-IgG, directed against the low
      affinity NGF receptor, also promotes the adhesion of S-16, PC12, and primary
      Schwann cells. In addition to adhesion, contact of S-16 Schwann cells with B2C11
      specifically induces morphological changes and robust proliferation. None of the
      other mAbs, including 192-IgG, induce proliferation of S-16 cells. These results
      provide evidence that CD9 may be involved in signaling, activation and growth
      regulation of cells in the nervous system.

PMID- 7823166
TI  - Regulation of c-ski transgene expression in developing and mature mice.
AB  - The control of c-ski transgene expression and muscle hypertrophy have been
      investigated in transgenic mice. In adult animals, the level of transgene
      expression is linked to the specialized phenotype of individual muscles, high
      levels occur in fast muscles and significantly lower levels in muscles with high
      metabolic activity (diaphragm, soleus). These findings have led us to propose
      that a threshold must be passed before ski-induced growth can occur. We now show
      that within fast muscles, induced hypertrophy uniquely involves IIb fibers. This
      pattern of expression is under development control; levels of c-ski mRNA are low
      in all muscles at birth. In the diaphragm, there is a sevenfold increase in c-ski
      message levels between 5 d and maturity. By contrast, in fast extensor digitorum
      longus and anterior tibial muscles, there is a 24-fold increase in levels between
      5 and 12 d postpartum. Muscle hypertrophy and antibody staining for c-ski protein
      in myofiber nuclei emerge concurrently. This pattern of c-ski expression
      parallels the appearance of IIb myosin heavy chain transcripts (Wydert et al.,
      1987) and differentiation of IIb fibers, suggesting that amplification of c-ski
      mRNA levels is linked to the development of IIb fiber specialization.
      Manipulations that are known to perturb IIb fiber development, neonatal
      denervation, and neonatally induced hypothyroidism inhibit high levels of c-ski
      expression and hypertrophy. In the adult fast EDL, denervation leads to rapid
      atrophy of IIb fibers and a significant decline in levels of c-ski mRNA. The
      results suggest that the environment of differentiated IIb fibers permits the
      expression of high levels of c-ski mRNA and this, in turn, induces hypertrophy.

PMID- 7823167
TI  - Cellular basis of EEG slow rhythms: a study of dynamic corticothalamic
      relationships.
AB  - A slow oscillation (< 1 Hz) has recently been described in intracellular
      recordings from the neocortex and thalamus (Steriade et al., 1993c-e). The aim of
      the present study was to determine the phase relations between cortical and
      thalamic neuronal activities during the slow EEG oscillation. Intracellular
      recordings were performed in anesthetized cats from neurons in motor and
      somatosensory cortical areas, the rostrolateral sector of the reticular (RE)
      thalamic nucleus, and thalamocortical (TC) cells from ventrolateral (VL) nucleus.
      The EEG was used as time reference for alignment of activities in different,
      simultaneously recorded neurons, including dual impalements of cortical cells as
      well as cortical and TC cells. The spontaneous EEG oscillation was characterized
      by slowly recurring (0.3-0.9 Hz) sequences of surface-positive (depth-negative)
      sharp deflections, often followed by oscillatory activity within the frequency
      range of sleep spindles (7-14 Hz) or at faster frequencies. Cortical and RE cells
      were similarly hyperpolarized during the depth-positive EEG waves and were
      depolarized during the depth-negative EEG deflections. In many instances, the
      cell depolarization was associated with oscillations at the spindle frequency or
      with tonic firing at rates related to the level of depolarization. TC neurons
      were hyperpolarized during the depth-positive EEG waves and displayed a series of
      IPSPs, at the spindle frequencies, during the depth-negative EEG waves. Depending
      on the membrane potential (Vm), TC cells could fire spike bursts at the onset of
      the EEG depth-negativity, or their firing could be delayed by subsequent IPSPs.
      The sequence of spontaneous EEG and cellular events described above also
      characterized the responses to cortical and thalamic stimulation. Simultaneous
      intracellular recordings of pairs of cortical cells or cortical and TC cells
      showed that spontaneous transitions from less synchronized to more synchronized
      EEG states were marked by a simultaneous hyperpolarization, coincident with an
      overt depth-positive EEG wave. We conclude that during low-frequency oscillatory
      states, characteristic of slow-wave sleep, neocortical and thalamic neurons
      display phase relations that are restricted to narrow time windows, and that
      synchronization results from a generalized inhibitory phenomenon. Moreover, EEG
      synchronization is reflected as active inhibition in TC neurons. That this
      pattern is also present in states of hypersynchronization, such as seizure
      activity, is shown in the following paper (Steriade and Contreras, 1994).

PMID- 7823168
TI  - Relations between cortical and thalamic cellular events during transition from
      sleep patterns to paroxysmal activity.
AB  - We investigated in anesthetized cats the progressive development from EEG
      synchronized sleep patterns to low-frequency (< 15 Hz) paroxysmal activities,
      most of them consisting of epileptic-like seizures with spike-wave (SW) complexes
      at 2-4 Hz. We used multisite extra- and intracellular recordings of neocortical,
      reticular thalamic (RE), and thalamocortical (TC) neurons, including dual
      impalements of cortical and TC cells. A subsample (40%) of TC cells discharged
      spike bursts at 2-4 Hz, in close time relation with the spiky, depth-negative
      field components of SW seizures in related neocortical areas. Full
      synchronization among TC cells that were resonant with the cortical seizure
      activity was progressively reached toward the end of the SW paroxysm. The
      remaining TC cells (60%) were inhibited during the cortical SW seizures. We show
      that the duration and amplitude of hyperpolarization in TC cells paralleled the
      extent of cortical EEG paroxysm. Dual intracellular recordings of cortical and TC
      neurons demonstrate that during the cortical SW seizure, consisting of a tonic
      depolarization with superimposed paroxysmal spike bursts, the simultaneously
      recorded TC neurons displayed a tonic hyperpolarization associated with
      repetitive IPSPs, closely time related with cortical cell bursts. The inhibition
      of TC cells was presumably mediated by GABAergic RE thalamic neurons. Indeed,
      simultaneously recorded RE and TC neurons during the cortical SW paroxysm showed
      that cortical and RE cell excitation was accompanied by corresponding IPSPs in TC
      cells. We emphasize the progressive development from sleep patterns to some forms
      of epileptic-like activities. We propose that the inhibitory processes found in a
      significant number of TC cells during cortical SW seizures may contribute to the
      loss of consciousness, due to obliteration of synaptic transmission through the
      thalamus.

PMID- 7823169
TI  - Chronic depolarization prevents programmed death of sympathetic neurons in vitro
      but does not support growth: requirement for Ca2+ influx but not Trk activation.
AB  - Continuous exposure of many types of neurons in cell culture to elevated
      concentrations of K+ greatly enhances their survival. This effect has been
      reported to be mediated by a sustained rise of cytoplasmic free Ca2+
      concentration caused by influx of Ca2+ through voltage-gated channels activated
      by K(+)-induced chronic depolarization. In this report we investigate the effects
      of elevated K+ on the programmed death that embryonic rat sympathetic neurons
      undergo in culture when deprived of NGF. Elevated K+ in the culture medium did
      not significantly prevent death of NGF-deprived cells until after the third day
      following plating of embryonic day 21 neurons. On the fifth day after plating,
      incrementally increasing K+ concentrations in the culture medium from 5 to 100 mM
      caused chronic depolarization of neurons and had a biphasic effect on survival of
      NGF-deprived cells. Enhanced survival was steeply related to membrane potential,
      increasing from no enhanced survival in cells held at potentials between -51 and 
      34 mV to 90-100% of control survival at about -21 mV. At potentials positive to 
      21 mV, survival decreased. Associated with the chronic depolarization was a
      sustained rise of steady-state free Ca2+ concentration that showed a biphasic
      relationship to membrane potential roughly similar to that exhibited by survival.
      Steady-state Ca2+ concentration increased with increasingly lower membrane
      potentials to a peak at about -23 mV (to approximately 240 nM from approximately
      40 nM at about -51 mV) and then decreased at more positive potentials. The
      elevation of intracellular Ca2+ was largely blocked by dihydropyridine and
      phenylalkylamine Ca2+ channel antagonists and was potentiated by a
      dihydropyridine Ca2+ channel agonist. Neither the rise of Ca2+, or survival was
      affected by the Ca2+ channel antagonist, omega-conotoxin. Therefore, the Ca2+
      elevation was probably caused by Ca2+ influx through L-type, but not N-type,
      channels. Antagonists of L channels blocked both survival and the sustained
      increase of steady-state free Ca2+ at similar concentrations, suggesting that the
      relevant factor determining survival of depolarized cells was Ca2+ influx rather
      than some other effect of depolarization. Surprisingly, however, there was no
      clear correlation between the sustained rise of Ca2+ and survival. Some membrane
      potentials that induced similar increases of Ca2+ concentration produced widely
      different levels of survival. While chronic depolarization promoted survival of
      neurons in the absence of NGF, cells supported in this manner showed little
      growth as measured by neurite extension, total cellular protein, and mean somal
      diameter.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7823170
TI  - Functional synaptic connections made by regenerated retinal ganglion cell axons
      in the superior colliculus of adult hamsters.
AB  - Regenerated synaptic connections in the damaged mammalian visual system were
      studied in adult hamsters in which retinal ganglion cells (RGCs) regrew their
      axons through autologous peripheral nerve grafts directed from the stump of the
      transected optic nerve to the superior colliculus (SC). Unitary responses to
      illumination of small areas of the visual field were recorded within the
      superficial laminae of the reinnervated SC 23 to 60 weeks after grafting. Each
      element of a typical bursting response to light consisted of a terminal potential
      (TP) (half width 164 +/- 25 microseconds, amplitude up to 171 microV) arising
      from a regenerated RGC axon terminal arborization, followed at a latency of 268
      +/- 63 microseconds by a longer duration negative focal synaptic potential (FSP)
      (half width 938 +/- 396 msec, amplitude up to 188 microV) reflecting EPSPs in
      neurons within the terminal field of the regenerated RGC axon. The FSP but not
      the TP was attenuated in a dose-dependent manner by iontophoretic application of
      GABA. In some cases spikes arose from FSPs after the first two or three impulses
      of a train, presumably reflecting summation of EPSPs to threshold for excitation
      in SC neurons contacted by the regenerated RGC axon terminals. Up to one-third of
      the area of the SC can be infiltrated by arborizations of the regenerated RGC
      axons that enter the SC through a nerve graft inserted in the lateral aspect of
      the SC. These experiments indicate that terminal arborizations of individual
      regenerated RGC axons can synapse with multiple neurons in the SC and that
      convergence of inputs from regenerated RGC axons is not required for activation
      of SC neurons in response to light.

PMID- 7823171
TI  - Immortalized murine striatal neuronal cell lines expressing dopamine receptors
      and cholinergic properties.
AB  - Immortalized hybrid cells were generated by somatic cell fusion of 18-d-old
      embryonic corpus striatum of the mouse strain C57BL/6J with the N18TG2
      neuroblastoma. One of the cell populations obtained was treated with a
      combination of 1 mM n-butyric acid and 10 microM SKF 38393 (a specific D1
      agonist), and a surviving cell population (E1X) was subcloned. Twenty-seven
      monoclonal cell lines were obtained and screened for the expression of striatal
      specific characteristics including gamma-aminobutyric acid (GABA), choline
      acetyltransferase (ChAT), acetylcholine (ACh), mRNA for specific dopamine
      receptors, and dopamine- and adenosine 3':5'-monophosphate-regulated
      phosphoprotein, M(r) 32,000 (DARPP-32), and functional D1 and D2 dopamine
      receptors. Neither the parent hybrid cell population (E1X) nor any of the
      monoclonal cell lines examined expressed GABA levels significantly different than
      that of the N18TG2 parent neuroblastoma cells (1.36 +/- 0.07 micrograms/mg
      protein). The range of ChAT activity in the monoclonal hybrid cell lines was 5.5
      +/- 0.3 to 921.3 +/- 97.4 pmol/min/mg protein. Two of the cell lines expressing
      ChAT activity (X52 and X58) contained ACh (49.64 +/- 4.23 and 1.78 +/- 0.07 ng/mg
      protein, respectively). The neuronal origin of four of the monoclonal hybrid
      lines was shown by their immunoreactivity, following differentiation with 10
      microM forskolin, to neurofilament protein, a neuron-specific marker. The
      monoclonal hybrid cell lines, but not the N18TG2 neuroblastoma, were shown to
      express an array of D1, D2, and D5 receptor mRNA as well as DARPP-32 mRNA. Two
      monoclonal cell lines expressed D1 receptor binding sites (X57, 29.2 +/- 4.5
      fmol/mg protein and X62, 43.8 +/- 6.8 fmol/mg protein) which mediated the
      stimulation of adenylate cyclase activity. One cell line, X58, expressed only D2
      dopamine receptors (80.9 +/- 9.8 fmol/mg protein) which were negatively coupled
      to adenylate cyclase activity. These findings suggest that the immortalized
      monoclonal hybrid cell lines are of neuronal origin and have incorporated
      elements of the medium spiny and cholinergic neurons of the developing striatum.

PMID- 7823172
TI  - Visual deprivation does not affect the orientation and direction sensitivity of
      relay cells in the lateral geniculate nucleus of the cat.
AB  - Visual deprivation in early life profoundly affects the characteristic
      sensitivity of visual cortical cells to stimulus orientation and direction.
      Recently, relay cells in the lateral geniculate nucleus (LGNd) have been shown to
      exhibit significant degrees of orientation and direction sensitivity. The effects
      of visual deprivation upon these properties of subcortical cells are unknown. In
      this study cats were reared from birth to 6-12 months of age in total darkness;
      the orientation and direction sensitivities of area 17 (striate cortex) and LGNd
      cells were compared. All cells were studied using identical quantitative
      techniques and statistical tests designed to analyze distributions of angles. The
      results confirm previous work and indicate that the orientation and direction
      sensitivities of cells in area 17 are profoundly reduced by dark rearing. In
      marked contrast, these properties of LGNd relay cells are unaffected. The result
      is that, unlike in the normal cat, in dark-reared cats the orientation and
      direction sensitivities of cells in the LGNd and visual cortex do not differ. It
      is concluded that (1) the orientation and direction sensitivities of cortical
      cells contribute little, if at all, to the sensitivities of LGNd cells since LGNd
      cells exhibit normal sensitivities even though the cortical cells projecting to
      them exhibit greatly reduced sensitivities and (2) during normal development
      intracortical mechanisms appear to expand upon and/or modify the weak orientation
      and direction sensitivities of their inputs. These intracortical mechanisms
      depend upon normal visual experience since in dark-reared cats, but not normal
      ones, the orientation and direction sensitivities of cells in the LGNd and visual
      cortex do not differ quantitatively or qualitatively.

PMID- 7823173
TI  - Endogenous GABA attenuates CNS white matter dysfunction following anoxia.
AB  - We studied the effects of GABA on anoxia-induced injury in CNS white matter using
      optic nerves exposed to 60 min of anoxia. Injury was assessed by recording pre-
      and postanoxic compound action potentials (CAPs). GABA (1 microM) significantly
      increased postanoxic CAP recovery when applied 60 min prior to anoxia. This
      effect was bicuculline (100 microM) insensitive, mimicked by baclofen (1 microM),
      blocked by GABA-B antagonists, and not mimicked by selective GABA-A agonists.
      GABA therefore acted at GABA-B receptors. High concentrations of GABA and
      baclofen did not influence recovery, possibly indicating GABA-B receptor
      desensitization at high agonist concentrations. Pertussis toxin (PTX) treatment
      reduced postanoxic CAP recovery in the presence of 1 microM GABA to control
      levels, indicating the recruitment of a G-protein-linked intracellular pathway.
      Protein kinase C (PKC) activation with 12-myristate 13-acetate (PMA) mimicked the
      effects of GABA. Inhibition of PKC with 1-(5-isoquinolinesulfonyl)-2
      methylpiperazine dihydrochloride (H7) or staurosporine reduced postanoxic
      recovery in the presence of GABA to lower levels than under control conditions,
      confirming the involvement of PKC in the protective effect of GABA and indicating
      that this GABA-B receptor/G-protein/PKC protective pathway might be active under
      control conditions. This was confirmed by the observation that GABA-B receptor
      blockade, in the absence of exogenous GABA, significantly reduced postanoxia
      recovery. Thus, activation of the protective mechanism under control conditions
      is due to endogenous GABA release. Increasing the level of endogenous
      extracellular GABA by blocking GABA uptake with 1 mM nipecotic acid also
      protected against anoxia. We propose a model where release of GABA in white
      matter helps to limit nerve fiber injury during anoxia via recruitment of a G
      protein/PKC pathway with subsequent phosphorylation of an unknown target protein.

PMID- 7823174
TI  - Conditioned fear-induced changes in behavior and in the expression of the
      immediate early gene c-fos: with and without diazepam pretreatment.
AB  - The synthesis of Fos, the protein product of the immediate early gene c-fos, was
      used to map metabolically some of the neural substrates of conditioned fear in
      the rat. Analysis of the behaviors emitted by the rats during the test session
      provided strong evidence that the conditioning procedure was effective. Exposure
      to the environment in which they had previously received footshock significantly
      increased the number of Fos-like immunoreactive neurons in nearly 50 brain
      regions, both cortical and subcortical. Among the structures showing the most
      dramatic increases in fear-induced c-fos expression were the cingulate, piriform,
      infralimbic, and retrosplenial cortices, the anterior olfactory nucleus,
      claustrum, endopiriform nucleus, nucleus accumbens shell, lateral septal nucleus,
      various amygdalar nuclei, paraventricular thalamic nucleus, ventral lateral
      geniculate nucleus, the ventromedial, lateral, and dorsal hypothalamic nuclei,
      the ventral tegmental area, and the supramammillary area. These data demonstrate
      that a relatively simple classical conditioning procedure activates a large
      number of widely dispersed cortical and subcortical structures. Some of the
      structures showing increased c-fos expression have important autonomic functions
      and may therefore have reflected centrally mediated changes in blood pressure and
      respiration produced by the anxiogenic stimuli. In a second experiment, the
      effects of pretreatment with the anxiolytic drug diazepam (2.5, 5.0, or 10 mg/kg)
      were evaluated. The benzodiazepine produced dose-related decreases in the
      frequency of crouching (freezing) elicited by the aversively conditioned
      contextual cues. Diazepam also produced dose-related decreases in conditioned
      stress-induced c-fos expression in all but one structure, the effects being
      statistically significant in 38 of 60 sampled structures. Diazepam dose
      dependently increased fear-induced c-fos expression in the central nucleus of the
      amygdala. There was considerable regional variability with respect to sensitivity
      to diazepam, the retrosplenial cortex and the supramammillary area being the only
      two structures to show decreases after the lowest dose of diazepam. In contrast,
      the entorhinal cortex, nucleus accumbens core, ventromedial and posterior
      hypothalamic nuclei, median raphe, and locus coeruleus were particularly
      resistant to diazepam, all failing to show statistically significant decreases in
      conditioned fear-induced c-fos expression even at the highest dose. The extent to
      which diazepam decreased conditioned stress-induced c-fos expression was
      unrelated to previous estimates of benzodiazepine receptor density in the sampled
      structures.

PMID- 7823175
TI  - Alcohol selectively attenuates stress-induced c-fos expression in rat
      hippocampus.
AB  - The ability of ethyl alcohol to modify responses to stress has been well
      documented (cf. Pohorecky, 1990). However, the structural substrate mediating
      these effects of alcohol remains undefined. Using immediate early gene (IEG)
      expression in the brain as a marker of altered neuronal response, we investigated
      the effect of acute alcohol exposure on the activity of brain regions of rats
      exposed to 15 min of restraint stress. Immunocytochemical localization c-Fos
      protein demonstrated that restraint stress led to an induction of c-Fos
      expression in several brain structures including cingulate and piriform cortex,
      cortico-amygdaloid and hippocampo-amygdaloid transition zones, hippocampus,
      hypothalamus, supramammillary nucleus, and centromedial nucleus of thalamus. An
      intraperitoneal injection of 2 g/kg alcohol prior to stress decreased c-Fos
      expression in several but not all of these structures. In particular, alcohol
      strongly attenuated the stress-induced expression of c-Fos in hippocampus and
      cingulate cortex. Using slot-blot hybridization, significant induction of c-fos
      mRNA after restraint stress was demonstrated both in hippocampus and cortex, but
      prior alcohol exposure specifically attenuated c-fos induction only in the
      hippocampus. The response of c-fos mRNA expression to stress and alcohol differed
      from the effects on jun-B, c-jun and jun-D mRNA levels. Perhaps surprisingly,
      acute exposure to alcohol in otherwise unstressed rats did not induce significant
      changes in expression of IEGs in comparison to control (saline-injected) animals
      even with doses sufficient to elevate plasma corticosterone. In summary, these
      studies demonstrate a selective sensitivity of stress-induced activity of neurons
      of hippocampus and cingulate cortex to acute alcohol exposure.

PMID- 7823176
TI  - Delta and mu enkephalins inhibit spontaneous GABA-mediated IPSCs via a cyclic AMP
      independent mechanism in the rat hippocampus.
AB  - The effects of enkephalins selective for delta and mu opioid receptors on
      inhibitory postsynaptic currents (IPSCs) mediated by GABA were studied in
      chloride-loaded CA1 pyramidal neurons in adult rat hippocampal slices. The mu
      agonist DAMGO (0.1 microM) significantly reduced the amplitudes of evoked
      monosynaptic IPSCs, recorded following the antagonism of excitatory glutamate
      receptors, and this effect was reversed by the mu antagonist CTOP (1 microM). The
      selective delta receptor agonists DPDPE and D-Ala2-deltorphin II (both 0.1-0.5
      microM) had no effect on these evoked currents. In contrast, the frequency of
      tetrodotoxin-resistant spontaneous miniature GABA-mediated currents (m-IPSCs) was
      significantly reduced by both DPDPE (0.1-0.5 microM) and DAMGO (0.1-0.5 microM),
      while the amplitudes of these events were unaltered. These effects were reversed
      by the selective delta antagonist ICI 174,864 (1 microM) and the selective mu
      antagonist CTOP (1 microM), respectively. To investigate the mechanisms of this
      mu and delta receptor-mediated modulation of GABA release, and the possible
      involvement of a cAMP-sensitive K+ conductance, spontaneous action potential
      dependent IPSCs (s-IPSCs) were measured following pretreatment with 8-bromo-cAMP
      (8-Br-cAMP). 8-Br-cAMP (250 microM) had no effect alone on the amplitude or
      frequency of s-IPSCs, nor did it alter the inhibitory effects of the delta and mu
      agonists. These results indicate that delta and mu opioid receptor activation
      inhibits spontaneous GABA release, independently of cAMP, through direct actions
      at inhibitory nerve terminals, and that delta opioids inhibit spontaneous but not
      evoked GABA release in the hippocampus.

PMID- 7823177
TI  - Regulation of protease nexin-1 expression in cultured Schwann cells is mediated
      by angiotensin II receptors.
AB  - Protease nexin-1 (PN-1) is a potent inhibitor of serine proteases, such as
      thrombin and plasminogen activators, which is secreted into the extracellular
      space. Since PN-1 is induced following lesion of the sciatic nerve, the effect of
      substances known to accumulate at the site of injury was examined in primary
      cultures of Schwann cells. Among the cytokines, growth factors, mitogens,
      neurotrophins, and neuroactive peptides analyzed, only angiotensin II (Ang II),
      calcitonin gene-related peptide (CGRP), and vasoactive intestinal peptide (VIP)
      were found to regulate the expression of PN-1 on Schwann cells. While Ang II and
      CGRP caused downregulation, VIP acted as a positive modulator of PN-1.
      Displacement of Ang II binding using the selective ligands losartan and CGP 42112
      led to a severalfold increase of PN-1 protein and mRNA over basal levels,
      indicating that the observed effect was mediated by specific binding sites.
      Indeed, the presence of AT1 and AT2 angiotensin receptor subtypes was
      demonstrated in cultured Schwann cells as well as in the rat sciatic nerve.
      Moreover, the detection of angiotensinogen- and renin-mRNA in these cultures
      suggested an endogenous production of Ang II. This data identified one of the
      mechanisms regulating PN-1 synthesis. Altogether our results indicate that
      neuropeptides can differentially control the proteolytic activity of the
      microenvironment, providing new aspects of neuron-glia interactions in the intact
      tissue and following nerve injury.

PMID- 7823178
TI  - Cutaneous activation of the inhibitory L30 interneurons provides a mechanism for
      regulating adaptive gain control in the siphon withdrawal reflex of Aplysia.
AB  - The functional role of inhibition in the neural network underlying the siphon
      withdrawal response (SWR) of Aplysia was assessed by examining a recurrent
      circuit comprised of identified inhibitory interneurons (L30s), and excitatory
      interneurons (L29s). We previously showed that activity-dependent potentiation of
      the L30 inhibitory synapse onto L29 can regulate the net excitatory input
      elicited by tactile siphon stimulation onto siphon motor neurons (LFS cells)
      (Fischer and Carew, 1993a). To explore the functional significance of L30
      potentiated inhibition, we have examined how a behaviorally relevant stimulus
      that activates the L30 interneurons modulates the SWR circuit. Utilizing a
      reduced preparation, we show that weak tactile stimulation of the tail strongly
      activates the L30s, and leads to significant potentiation of the L30 synapse.
      Next, we demonstrate that similar weak tail stimulation produces significant
      inhibition of siphon tap-evoked responses in both L29 interneurons and LFS motor
      neurons. We further show that this form of inhibition is transient, having a time
      course of approximately 60 sec. Finally, we directly tested the role of the L30s
      in mediating this form of inhibition by hyperpolarizing two (of three) L30
      interneurons during tail stimulation. L30 inactivation significantly attenuated
      tail stimulation-induced inhibition of siphon-evoked input to both L29
      interneurons and LFS motor neurons. Based on these results, we suggest that L30
      potentiated inhibition may have an important adaptive role in optimizing the
      signal-to-noise ratio for activation of the SWR circuit by providing
      stabilization of SWR responsiveness under a wide range of environmental
      conditions.

PMID- 7823179
TI  - Interneurons and inhibition in the dentate gyrus of the rat in vivo.
AB  - Inhibitory cells are critically involved in shaping normal hippocampal function
      and are thought to be important elements in the development of hippocampal
      pathologies. However, there is relatively little information about the extent and
      pattern of axonal arborization of hippocampal interneurons and, therefore, about
      the sphere of influence of these cells. What we do know about these cells is
      based largely on in vitro slice studies, in which interneuronal interactions may
      be severely attenuated. The present study was carried out to provide a more
      realistic picture of interneuron influence. Intracellular recordings were
      obtained from dentate interneurons in the intact brain of anesthetized rats, and
      cells were intracellularly labeled with biocytin. The axonal arbors of two
      classes of dentate interneurons were traced through the hippocampus; each was
      found to extend long distances (up to half of the total septotemporal length of
      the hippocampus) perpendicular to the hippocampal lamellae and to target
      preferential strata. These results suggest that dentate interneurons have far
      reaching effects on target cells in distant hippocampal lamellae. One implication
      of this finding is that dentate neurons should receive more inhibitory synaptic
      drive in vivo than in slice preparations, in which many inhibitory axon
      collaterals are amputated. Synaptic responses to perforant path stimulation were
      examined in granule cells, mossy cells, and CA3 pyramidal cells in vivo, for
      comparison with previously published results from hippocampal slice studies. In
      vivo, all cell types showed excitatory synaptic responses that were brief and
      limited by robust IPSPs that were larger in amplitude and conductance than
      responses to comparable stimuli recorded in vitro. This difference could not be
      explained by a change in the intrinsic physiological properties of the cells in
      the slice preparation, because those parameters were similar in vivo and in
      vitro. We conclude that dentate gyrus inhibitory interneurons can affect the
      excitability of neurons in distant areas of the hippocampus, and that these
      distant influences cannot be appreciated in conventional in vitro preparations.

PMID- 7823180
TI  - A single identified interneuron gates tail-shock induced inhibition in the siphon
      withdrawal reflex of Aplysia.
AB  - The marine mollusc Aplysia has proven very useful for a mechanistic analysis of
      behavioral modification. Among the stimuli used to modify the behavior of
      Aplysia, a noxious stimulus, tail shock, is one of the most effective. In
      addition to the extensively analyzed facilitatory effects of tail shock, recent
      work has demonstrated that it also produces marked transient inhibition in reflex
      responses. Here we report that functional removal (by hyperpolarization or
      voltage clamp) of a single inhibitory interneuron, L16, can eliminate most, if
      not all, of the inhibition in the siphon withdrawal reflex circuit produced by
      tail shock. In addition, this interneuron is strongly activated by tail shock.
      Finally, direct intracellular activation of L16 does not, in itself, reliably
      produce inhibition, suggesting that L16 plays a gating role which is necessary
      for the expression of inhibition in the siphon withdrawal circuit. These results
      support the idea that behaviorally relevant neural modulation can be gated by a
      small number of neurons, in this case, by a single identified cell. Moreover,
      they indicate that in Aplysia, as in many other systems, the modulatory effects
      of a noxious stimulus are often funneled through a restricted neural locus before
      being distributed to the circuits actually responsible for generating the
      behavioral output.

PMID- 7823181
TI  - Representation of curved surfaces in responses of mechanoreceptive afferent
      fibers innervating the monkey's fingerpad.
AB  - The aim was to elucidate how the population of digital nerve afferents signals
      information about the shape of objects in contact with the fingerpads during fine
      manipulations. Responses were recorded from single mechanoreceptive afferent
      fibers in median nerves of anesthetized monkeys. Seven spherical surfaces were
      used, varying from a highly curved surface (radius, 1.44 mm; curvature, 694 m-1)
      to a flat surface (radius, infinity; curvature, 0 m-1). These were applied to the
      fibers' receptive fields, which were located on the central portion of a
      fingerpad. When the objects were located at the centers of the receptive fields,
      the responses of the slowly adapting fibers (SAIs) increased as the curvature of
      the surface increased and as the contact force increased. All SAIs behaved in the
      same way, differing only by a scaling factor (the sensitivity of the individual
      afferent). Responses of the rapidly adapting afferents were small and did not
      vary systematically with the stimulus parameters, and most Pacinians did not
      respond at all. Stimuli were applied at different positions in the receptive
      fields of SAIs to define the response profiles of the afferents (response as a
      function of position on the fingerpad). All SAIs had similarly shaped profiles
      for the same surface curvature and the shape differed for different curvatures.
      These profiles reflected the shape of the stimulus. An increase in contact force
      scaled these profiles upward. Thus, the population of digital nerve fibers
      signals unambiguous information about the shape and contact force of curved
      surfaces contacting the fingerpad.

PMID- 7823182
TI  - Lateral inhibition and granule cell synchrony in the rat hippocampal dentate
      gyrus.
AB  - Studies of patients with temporal lobe epilepsy and of experimental models of
      this disorder suggest that the hippocampal dentate gyrus may be a common site of
      seizure onset and propagation. However, the nature of the dentate "network
      defect" that could give rise to spontaneous, intermittent, and synchronous
      population discharges is poorly understood. We have hypothesized that large
      expanses of the dentate granule cell layer have an underlying tendency to
      discharge synchronously in response to afferent excitation, but do not do so
      normally because vulnerable dentate hilar neurons establish lateral inhibition in
      the granule cell layer and thereby prevent focal discharges from spreading to
      surrounding segments. To address this hypothesis, we (1) identified functionally
      independent segments of the granule cell layer; (2) determined whether discharges
      in one segment evoke lateral inhibition in surrounding segments; and, (3)
      determined if disinhibition induces normally independent segments of the granule
      cell layer to discharge synchronously. Simultaneous extracellular recordings were
      made from two locations along the longitudinal or transverse axes of the granule
      cell layer using saline- and bicuculline-filled electrodes that were glued
      together. Leakage of 10 mM bicuculline from the electrode tip produced no
      detectable spontaneous activity. However, single perforant path stimuli evoked
      multiple population spikes at the bicuculline electrode and simultaneous normal
      responses at the nearby saline electrode. The multiple spikes evoked at the
      bicuculline electrode did not propagate to, and were not detected by, the
      adjacent saline electrode, indicating functional separation between neighboring
      subgroups of granule cells. Paired-pulse stimulation revealed that multiple
      discharges were not only restricted to one segment of the granule cell layer, but
      strongly inhibited surrounding segments. This lateral inhibition in surrounding
      segments often lasted longer than 150 msec. Finally, we evaluated granule cell
      activity at two normally independent sites within the granule cell layer both
      before and after disinhibition was induced by high frequency stimulus trains or
      bicuculline injection. Following a 10 sec, 20 Hz perforant path stimulus train, 2
      Hz stimulation evoked virtually identical synchronized epileptiform discharges
      from normally separated sites. Similarly, intrahippocampal or intravenous
      bicuculline injection produced spontaneous synchronous epileptiform discharges
      throughout the granule cell layer. These results indicate that lateral or
      "surround" inhibition is an operant physiological mechanism in the normal dentate
      gyrus and suggest that afferent stimuli to a disinhibited dentate network evoke
      highly synchronized discharges from large expanses of the granule cell layer that
      are normally kept functionally separated by GABA-mediated inhibition.

PMID- 7823183
TI  - Serotonergic modulation of striatal dopamine measured with positron emission
      tomography (PET) and in vivo microdialysis.
AB  - Positron emission tomography and in vivo microdialysis were used to study
      serotonin's role in modulating striatal dopamine. Serial PET studies were
      performed in adult female baboons at baseline and following drug treatment, using
      the dopamine (D2) selective radiotracer, 11C-raclopride. The serotonergic system
      was manipulated by administration of the selective 5-HT reuptake inhibitor,
      citalopram, or by serotonergic (5-HT2) receptor blockade (using altanserin, a 5
      HT2 antagonist). 11C-Raclopride time-activity data from striatum and cerebellum
      were combined with plasma arterial input functions and analyzed by calculating a
      distribution volume as described previously (Logan et al., 1990). Additionally,
      in vivo microdialysis studies were performed in awake freely moving rats using
      similar pharmacologic challenges plus SR 46349B, a new highly selective 5-HT2
      receptor antagonist. Altanserin and SR 46349B increased extracellular striatal
      dopamine concentrations (35% and 910%, respectively) while altanserin decreased
      striatal 11C-raclopride binding (37%). Citalopram, however, decreased
      extracellular striatal dopamine concentrations (50%) and increased 11C-raclopride
      binding (33%). These data demonstrate that 5-HT-selective drugs produce changes
      in striatal dopamine that can be measured noninvasively with PET. Furthermore,
      the PET data obtained from anesthetized baboons is consistent with in vivo
      microdialysis data obtained from awake and freely moving rats. Finally, these
      studies have implications for understanding the therapeutic efficacy of atypical
      neuroleptics and their utility for treating schizophrenia and affective
      disorders.

PMID- 7823184
TI  - Receptor encoding of moving tactile stimuli in humans. I. Temporal pattern of
      discharge of individual low-threshold mechanoreceptors.
AB  - The response of 70 cutaneous, low-threshold mechanoreceptors in the human median,
      radial and inferior alveolar nerves to well controlled brush stimuli moving
      across the receptive field was quantitatively studied. Microneurography was used
      to obtain the response of each to multiple velocities from 0.5 to 32 cm/sec in at
      least two opposing directions. A high degree of response consistency was observed
      from the slowly adapting receptors to replication of the same stimulus and to a
      lesser, but significant degree from the fast adapting receptors. The evoked
      discharge reflected up to three partially overlapping phases of the moving
      stimulus: skin compression, indentation, and stretch. Although the overall
      discharge rate increased with both stimulus velocity and force, the spatial
      discharge pattern was preserved to a high degrees. In contrast, the discharge
      patterns differed for opposing and orthogonal directions. Reducing the area of
      skin surrounding the receptive field that was contacted by the moving stimuli had
      little effect on the evoked response. Individual mechanoreceptors display highly
      reliable differences to brush stimuli moving at different velocities. to brush
      stimuli moving at different velocities. Moreover, different directions of
      movement evoke differences in the discharge that are consistently observed upon
      replication of the same stimuli. Despite the richness and consistency in the
      spatial discharge pattern displayed by individual receptors, it is argued that
      the details of the patterns are not likely used by the CNS to infer information
      about direction and velocity of movement across the skin. Rather, the intensity
      of discharge is proposed as a plausible information-bearing attribute of the
      stimulus-evoked response.

PMID- 7823185
TI  - Receptor encoding of moving tactile stimuli in humans. II. The mean response of
      individual low-threshold mechanoreceptors to motion across the receptive field.
AB  - The mean firing rate evoked in 70 cutaneous, low-threshold mechanoreceptors in
      the human median, radial, and inferior alveolar nerves by stimulus motion across
      the skin was quantitatively studied. Moving stimuli, controlled for velocity,
      direction, and length of skin traversed, were provided by a servo-controlled
      motor that carried a brush across the receptive field. Each unit was studied with
      stimuli delivered at multiple velocities from 0.5 to 32 cm/sec in at least two
      opposing directions. A power function provided an excellent description of the
      MFR-versus-velocity relationship. The exponent n was interpreted to reflect the
      receptor's sensitivity to changes in stimulus velocity, and the multiplicative
      constant c, the predicted response to stimuli moving at 1.0 cm/sec. The fast
      adapting mechanoreceptors exhibited higher sensitivity to stimulus velocity than
      the slowly adapting mechanoreceptors. The mean velocity at which the fast
      adapting units were predicted to first respond to movement was also higher.
      Estimates of n, c, or both differed significantly for stimuli delivered in
      opposing directions for more than 70% of the mechanoreceptors. No direction of
      motion consistently led to power function parameters with higher values so as to
      suggest a "preferred" regional direction of motion for the entire population.
      Neither the directional difference in n nor c could be attributed to directional
      differences in the forces applied across the receptive fields. These findings
      suggest that information about velocity and direction is represented in the mean
      firing rate responses evoked in the population of mechanoreceptors activated by a
      moving tactile stimulus.

PMID- 7823186
TI  - Localization of GAT-1 GABA transporter mRNA in rat striatum: cellular
      coexpression with GAD67 mRNA, GAD67 immunoreactivity, and parvalbumin mRNA.
AB  - The cellular localization and neurochemical phenotype of cells expressing the GAT
      1 GABA transporter was investigated in the adult rat dorsal striatum using single
      and dual in situ hybridization and immunocytochemical techniques. Cellular sites
      of GAT-1, GAD67, and parvalbumin mRNAs were visualized using a combination of
      radioactive and alkaline phosphatase-labeled oligonucleotides and emulsion
      autoradiography; GAD67 immunoreactivity was detected using a polyclonal antibody
      (K2) and 3'3"-diaminobenzidine. Two types of GAT-1-positive striatal cells were
      detected: (1) those expressing an abundance of GAT-1 mRNA, and (2) those
      expressing low/undetectable amounts of message. This study focused on the
      striatal cells expressing an abundance of GAT-1 mRNA; these cells accounted for
      approximately 3-5% of all striatal neurons and were detected scattered sparsely
      throughout the striatal complex. Dual in situ hybridization and
      immunocytochemical studies established that all cells enriched in GAT-1 mRNA also
      expressed high levels of GAD67 mRNA and were strongly GAD67 immunopositive; the
      converse was also found to be the case, the two hybridization signals having
      identical distribution patterns. Further dual in situ hybridization studies
      established that approximately 60% of these high GAD67/GAT-1 cells expressed
      parvalbumin mRNA, a marker of one population of striatal interneurons, and had an
      average cross-sectional area of 152.40 microns 2. The chemical phenotype of the
      remaining 40% of high GAD67/GAT-1 cells was not determined, although the average
      cross-sectional area of these cells (102.48 microns 2) was significantly smaller
      than GAT-1/GAD67/parvalbumin cells; these cells were detected in all striatal
      regions and are likely to correspond to another population of striatal GABAergic
      interneuron.

PMID- 7823188
TI  - Cortisol inhibition of calcium currents in guinea pig hippocampal CA1 neurons via
      G-protein-coupled activation of protein kinase C.
AB  - The inhibition of voltage-activated Ca2+ channel currents by cortisol
      (hydrocortisone), the principal glucocorticoid in man and guinea pig, was
      examined in freshly dissociated pyramidal neurons from the adult guinea pig
      hippocampal CA1 region using whole-cell voltage-clamp recordings. Steady-state
      inhibition by cortisol of the peak Ca2+ channel current evoked by depolarization
      from -80 to -10 mV increased in a concentration-dependent fashion, with a maximal
      inhibition of 63 +/- 4% of the total current at 100 microM. Cortisone had a
      maximal 17 +/- 2% inhibition at 10 microM. Corticosterone and the metabolite
      allotetrahydrodeoxycorticosterone exhibited a plateau of inhibition of around 15%
      and 25%, respectively, between 10 pM and 100 nM; both compounds continued to
      inhibit at concentrations > 10(-7) M. Analysis of tail currents at -80 mV showed
      that cortisol and corticosterone had no effect on the voltage-dependent
      activation or deactivation of the Ca2+ channel current. However, cortisol slowed
      the activation of the current. Cortisol inhibited both the N-type or omega
      conotoxin (CgTX)-sensitive, and the L-type or nifedipine (NIF)-sensitive Ca2+
      channel current but had no effect on the CgTX/NIF-insensitive Ca2+ channel
      current. In neurons isolated from pertussis toxin (PTX)-treated animals, the
      cortisol inhibition was significantly diminished. Intracellular dialysis with GDP
      beta-S (500 microM) or with the specific inhibitors of protein kinase C (PKC),
      the pseudosubstrate PKC inhibitor (PKCI 19-31) (2 microM) and bisindolylmaleimide
      (BIS) (1 microM) significantly diminished the cortisol inhibition of the Ca2+
      channel current. The specific inhibitor of cAMP-dependent protein kinase (PKA)
      inhibitor, Rp-cAMPS (100 microM) had no effect.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7823187
TI  - The organization of the inner nuclear layer of the rabbit retina.
AB  - The initial goal of this study was to establish an accounting of the major
      classes of cells present in the inner nuclear layer (INL) of the rabbit's retina.
      Series of 80-100 radial sections 1 micron thick were cut from retinal blocks
      dissected at intervals along the vertical meridian. They were photographed at
      high magnification in the light microscope. By visualizing the initial segments
      of processes leaving the somata, we could identify each cell as a bipolar,
      amacrine, horizontal, or Muller cell. The identifications made by light
      microscopy were confirmed by electron microscopy of alternating ultrathin
      sections. On average, bipolar cells made up 41% of the total INL cells, amacrine
      cells 32%, horizontal cells 1.5%, and Muller cells 24%. These fractions varied
      relatively little across the retina or among different animals. We next
      immunolabeled the rod bipolar cells of whole-mounted retinas with antibodies
      against protein kinase C, using FITC as the visualizing agent. The same retinas
      were counterstained with a DNA-binding probe that fluoresces at longer
      wavelengths. Serial optical horizontal sections of the double-labeled wholemounts
      were made by confocal microscopy. On average, rod bipolars accounted for 10% of
      the total INL cells. By subtraction, the cone bipolars made up 31% of the total
      cells. We conclude that cone bipolars substantially outnumber rod bipolars, even
      in a retina in which rods outnumber cones by more than 20:1. Using the base of
      reference created here, a similar analysis can be carried out for other
      subclasses of retinal neuron. Because the analysis does not depend on absolute
      cell densities or corrections for shrinkage, data acquired by different
      histochemical techniques may be combined.

PMID- 7823189
TI  - Eye movements in monkeys with local dopamine depletion in the caudate nucleus. I.
      Deficits in spontaneous saccades.
AB  - The basal ganglia contribute to the suppression and initiation of saccadic eye
      movements through the inhibitory connection from the substantia nigra pars
      reticulata (SNr) to the superior colliculus. This mechanism consists of serial
      and parallel connections, which are mostly inhibitory and GABAergic. Dopamine is
      known to exert powerful modulatory effects on the basal ganglia function, but its
      nature and mechanism are still unclear, especially in relation to voluntary
      behavior. The purpose of this series of investigation was to study the role of
      dopamine in the control of saccadic eye movements. We examined, in the monkey,
      whether and how the deficiency of the nigrostriatal dopaminergic innervation
      affects saccadic eye movements. The present article is focused on spontaneous
      saccades that the monkey made with no incentive to obtain reward; the next paper
      will describe task-specific saccades. Using an osmotic minipump we infused 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) unilaterally into the head-body
      junction of the caudate nucleus of monkeys where presaccadic neurons were
      clustered. Tyrosine hydroxylase activity, visualized using an immunohistochemical
      method, decreased locally around the injection site with some effects extending
      into the ipsilateral putamen and locally in the ipsilateral substantia nigra.
      Changes of eye movements started to appear 3-5 d after starting the infusion.
      Spontaneous saccades became less frequent. The area scanned by the saccades
      became narrower and shifted to the hemifield ipsilateral to the infusion site.
      The saccade amplitudes and peak velocities decreased; durations were prolonged.
      These effects were more prominent for saccades directed toward the side
      contralateral to the infusion site. These monkeys showed no obvious skeletomotor
      symptoms. These results suggest that the local deprivation of the dopaminergic
      innervation in the caudate nucleus facilitates neuronal activity of the SNr
      leading to suppression of saccadic eye movements.

PMID- 7823190
TI  - Eye movements in monkeys with local dopamine depletion in the caudate nucleus.
      II. Deficits in voluntary saccades.
AB  - Unilateral infusion of MPTP into the monkey caudate nucleus produced deficits in
      task-specific saccades, in addition to the deficits in spontaneous eye movements
      (preceding article). We trained three monkeys to perform two kinds of saccade
      tasks: (1) saccade task for eliciting visually guided saccades and (2) delayed
      saccade task for eliciting memory-guided saccades. After the MPTP infusion,
      dopaminergic function, estimated by tyrosine hydroxylase (TH) immunoreactivity,
      was shown to be decreased locally around the infusion site at the head-body
      junction of the caudate. We found that the deficits were prominent in the
      saccades directed to the side contralateral to the infusion (contralateral
      saccades). Memory-guided saccades were sometimes misdirected to the ipsilateral
      side even when the cue stimulus was presented on the contralateral side. Among
      the parameters of saccades, a selective change was found in the saccade latency:
      the latency was prolonged consistently in contralateral memory-guided saccades.
      The amplitude and velocity of saccades decreased in contralateral saccades,
      either memory guided or visually guided. The duration of saccades tended to
      increase in visually-guided saccades and memory-guided saccades, in both
      directions. Only one monkey, in which the decrease in TH activity included a
      large part of the putamen and the head of the caudate, showed prolongation of
      manual reaction time for lever release.

PMID- 7823191
TI  - Differential expression of two cell surface proteins, neuropilin and plexin, in
      Xenopus olfactory axon subclasses.
AB  - Immunohistochemistry by using monoclonal antibodies named A5 and B2, which
      specifically recognize cell surface proteins the neuropilin and the plexin,
      respectively, revealed that olfactory axons in Xenopus tadpoles were classified
      into several subgroups by virtue of the expression levels of these two cell
      surface molecules. The vomeronasal axons expressed the plexin but not the
      neuropilin. The plexin-positive and neuropilin-negative vomeronasal axons form a
      discrete fiber bundle, even after they joined with the principal olfactory axons.
      However, the principal olfactory axons were divided into at least two subclasses;
      the neuropilin-predominant axons which expressed high levels of the neuropilin
      and low levels of the plexin, and the plexin-predominant axons which expressed
      high levels of the plexin and low levels of the neuropilin. Within the olfactory
      nerve the pathways for these two principal olfactory axon subclasses were
      initially intermingled with each other, but were gradually segregated throughout
      their courses from the nose to the cerebrum. Eventually, the neuropilin
      predominant and the plexin-predominant principal olfactory axon subclasses
      projected to specified glomeruli in topographically related regions within the
      main olfactory bulb. Neuroanatomical tracings of the olfactory projection also
      confirmed the gradual segregation of the pathways for the principal olfactory
      axons. These results allow us to speculate that both the neuropilin and the
      plexin are involved in axon interactions, and play roles in the organization of
      the precise patterns of the olfactory pathway and projection.

PMID- 7823192
TI  - PACE: a unique career development program.

PMID- 7823193
TI  - Can ICUs be used more efficiently?

PMID- 7823194
TI  - Evaluation of a nursing documentation system revision.

PMID- 7823195
TI  - Disciplinary counseling process.

PMID- 7823196
TI  - Legal concerns related to workers with HIV or AIDS.

PMID- 7823197
TI  - Cultural transformation.

PMID- 7823198
TI  - The effect of ambulatory oncology nursing practice models on health resource
      utilization. Part 1, Collaboration or compliance?
AB  - The role of the nurse in ambulatory oncology care varies widely based on the
      setting and the philosophy of its practitioners and administrators. In an era of
      steadily decreasing monetary resources, assessing the effect of the activities of
      the ambulatory oncology nurse on economic outcomes related to cancer patients is
      imperative. A retrospective comparative study identified differences between two
      basic economic concepts--complement (compliance) and substitute (collaboration).
      Based on these concepts and the study results, Part 1 discusses two models of
      ambulatory oncology nursing practice delineated: the Nurse Complement Model, and
      the Nurse Substitute Model. Part 2 will present the direct but differing impact
      of these models on the effectiveness and efficiency of oncology patient care.

PMID- 7823199
TI  - Psychiatric emergency service. Using available resources.
AB  - When psychiatric patients come to hospital emergency departments for care, unique
      problems occur. Staff members are not prepared for this type of patient, and
      resources are strained. The authors discuss a collaborative nurse consultation
      service used to address this issue in a rural setting.

PMID- 7823201
TI  - Applying just-in-time philosophy to healthcare.
AB  - Nurse executives need to review what is working in other industries to see if
      similar techniques and philosophies can help the healthcare industry. The authors
      review the manufacturing philosophy supporting the just-in-time method and apply
      some of its principles to healthcare to improve operations and operating margins.

PMID- 7823200
TI  - Professional practice model research collaboration. Issues in longitudinal,
      multisite designs.
AB  - Implementing and evaluating professional practice models in dynamic healthcare
      settings is difficult and poses unique problems for nurse researchers and
      administrators. The authors describe issues associated with collaborating during
      the conduct of longitudinal studies.

PMID- 7823202
TI  - Alternative revenue sources for nursing departments.

PMID- 7823203
TI  - Program evaluation. Key to success.
AB  - In searching for the ideal model to deliver quality patient care in a cost
      effective manner, nursing has developed many patient care delivery models. These
      models, often lacking an evaluation component, were not optimally implemented.
      The authors present evaluation as a dynamic process resulting in ongoing changes,
      which strengthen a system. Focusing on alternative approaches, roles of key
      players, and evaluation procedures, specific guidelines for effectively
      evaluating a program are presented.

PMID- 7823204
TI  - Variable hospital accounting practices: are they fair for the nursing department?

PMID- 7823205
TI  - Accounting for nursing costs by DRG.

PMID- 7823206
TI  - Reconceptualizing organizational commitment.
AB  - Currently, vacancy rates and nursing turnover are at low levels, indicating that
      nurses are staying in their jobs for longer periods of time. The reasons for
      decreased job mobility for nurses are varied, but this development has
      ramifications for nurse administrators and managers. The new challenge will be to
      enhance the motivation of the nurse who will stay in a job for a longer term.
      This report of a study to further explore different types of organizational
      commitment with a nursing population gives new insight into why nurses stay in
      their jobs and the implications this has for the organization.

PMID- 7823207
TI  - Computerized documentation in home health.
AB  - Computerized documentation in community health nursing is only now receiving the
      attention it deserves. The authors explain one agency's experience with adapting
      a computerized clinical documentation system to visiting nurses' needs and the
      nurses' responses to the process.

PMID- 7823208
TI  - Computerization of patient acuity and nursing care planning: new approach to
      improved patient care and cost-effective staffing.

PMID- 7823209
TI  - Quality assurance: evaluate thyself.

PMID- 7823210
TI  - Credentialing, privileging, and nursing bylaws: assuring accountability.

PMID- 7823211
TI  - Association of IBM's "A Plan for Life" health promotion program with changes in
      employees' health risk status.
AB  - To evaluate the association of participation in IBM's "A Plan for Life" program
      with changes in blood pressure, serum total, high-density lipoprotein, and non
      high-density lipoprotein cholesterol, body mass index, and cigarette smoking, we
      compared changes in these measures over a 1- to 5-year period among program
      participants and nonparticipants initially found to be at risk. After adjustment
      for age, sex, time to follow-up, and baseline values, the proportion of
      participants no longer at high risk was significantly greater than the
      corresponding proportion of nonparticipants in the areas of blood pressure total
      and non-high-density lipoprotein cholesterol and smoking cessation.

PMID- 7823212
TI  - Training the clinician-manager. Assessing the reality.
AB  - Occupational medicine residents at the University of Arizona have been introduced
      to administrative skills and issues as part of residency training since 1983. A
      questionnaire survey of 17 program graduates was conducted to assess
      effectiveness of training and applicability of skills to present job position.
      Seventeen of the graduates surveyed (100%) returned a completed questionnaire.
      Graduates rated the extent to which certain training activities improved
      administrative skills, such as community-based rotations, a 1-month
      administration rotation, chief resident responsibilities, committee work, program
      or clinic administration, and residency training overall. Although ratings
      overall were low, we believe this stems from the need for training that residents
      discover on the job. The survey emphasized the importance of administrative
      training during the residency years and underscored the need for renewed training
      efforts on our part.

PMID- 7823213
TI  - Evaluation of current perception threshold testing as a screening procedure for
      carpal tunnel syndrome among industrial workers.
AB  - Eighty-four workers participated in a work-site screening program designed, in
      part, to estimate the prevalence of carpal tunnel syndrome (CTS). Each worker
      completed a discomfort survey, limited electrodiagnostic testing of the median
      and ulnar sensory nerves in each wrist, and current perception threshold (CPT)
      testing in the right 2nd digit using the NEUROMETER CPT device. A subset of study
      participants also completed CPT testing in digit 5 on the right (n = 33).
      Comparisons were made among the CPT results, symptoms consistent with CTS, and
      electrophysiologic findings. The CPT results correlated poorly with
      electrophysiologic parameters from the same nerve distribution, and CPT results
      were statistically unrelated to self-reported symptoms that may be suggestive of
      CTS. The test performance characteristics of CPT testing (sensitivity,
      specificity, positive predictive value, and negative predictive value) were low
      in comparison with electrodiagnostic measurements and self-reported symptoms
      consistent with CTS. The electrophysiologic results were significantly associated
      with the constellation of symptoms that are consistent with CTS. On the basis of
      these results, CPT testing cannot be recommended as a screening procedure for
      identification of possible cases of CTS among active industrial workers.

PMID- 7823214
TI  - Epidemiology of back injury in university hospital nurses from review of workers'
      compensation records and a case-control survey.
AB  - Reviewing Workers' Compensation records for back injury from a large university
      hospital for a 2-year period, we found a yearly incidence of lost work time back
      injury among nurses of 2.0% per year, exceeded only by physical plant staff, who
      had a rate of 3.5%. Nurses' aides had an injury rate 3.3-fold higher than
      registered nurses and licensed practical nurses and higher than any other
      occupational group. We compared 100 cases of nurses with back injury in the
      previous 2 years with 197 noninjured control subjects using a mailed 40-item
      questionnaire. Multivariate logistic modelling showed that prior nonback injury
      and performing combined lifting activities were statistically significant risk
      factors for back injury, and being overweight approached significance, after
      adjusting for the effects of age, gender, and each of the evaluated risk factors.

PMID- 7823215
TI  - Construction occupations, asbestos exposure, and cancer of the colon and rectum.
AB  - Colorectal cancer affects more than 157,000 Americans annually. Occupational risk
      from exposure to asbestos dust has been implicated, leading us to explore further
      the possible association between colorectal cancer and asbestos. Two hundred
      sixty-one cases of colon and rectal cancer and 183 control cases were identified
      within a large, population-based case-control study conducted in southeast
      Michigan. Employment in occupations historically known to involve heavy exposure
      to asbestos was used as a surrogate for asbestos exposure. Cancers of the colon
      showed reduced odds ratios. Our findings differ substantially from those of the
      previous studies showing elevated risk. Further study is needed to address the
      same question, with specified asbestos exposure assessment and control for
      potentially significant confounders such as physical activity and diet.

PMID- 7823216
TI  - Vibration sensibility testing in the workplace. Day-to-day reliability.
AB  - Loss of vibration sensibility has been suggested as an early indicator of
      peripheral compression neuropathy, including carpal tunnel syndrome. Although
      vibration sensibility has been used frequently to evaluate carpal tunnel
      syndrome, the day-to-day reliability of vibration measurements in an industrial
      population measured at the workplace has not been assessed. Vibration sensibility
      testing was performed at the university ergonomics laboratory on 50 volunteers
      (100 hands) and at a newspaper company on 50 workers (100 hands). Vibration
      perception and disappearance thresholds were measured on two occasions separated
      by 3 to 5 days. Student's t tests indicated no significant differences between
      the first and second tests or between the two groups. Pearson product-moment
      correlations for test-retest reliability were lower in the industry group but
      were relatively high despite the less than optimal testing conditions. Our
      findings suggest that vibration sensibility measurements are reliable from day to
      day not only in the laboratory but also in the workplace.

PMID- 7823217
TI  - Medicine's industrial revolution is here. Rally the Luddites.

PMID- 7823218
TI  - An employee was noted making verbal threats to his supervisor concerning a
      potential adverse performance review. What is the potential for physical harm in
      this situation?

PMID- 7823219
TI  - Workers' compensation.

PMID- 7823220
TI  - The economic impact of depression in a workplace.
AB  - Epidemiological studies hold that depressive disorders are among the most common
      forms of mental illness in the population and should produce a substantial
      economic impact upon corporate America. However, only a few studies have examined
      the economic impact of depression in the workplace. A study of the medical and
      disability costs of depressive disorders was conducted at the First Chicago
      Corporation. In this analysis, short-term disability data, medical plan costs and
      Employee Assistance Program referral data for depressive disorders were compared
      with selected common chronic medical conditions. The average length of disability
      and the disability relapse rate was greater for depressive disorders than for the
      comparison medical groups. Depressive disorders were also found to have the
      largest medical plan costs of all behavioral health diagnoses. Finally,
      depressive disorders proved to be the most common Axis-I-level diagnosis
      encountered in the Employee Assistance Program. These findings have important
      implications for medical benefit plan design, disability plan management, and
      occupational health professionals' training. The observed higher prevalence of
      these disorders in women force their recognition as a women's health issue.

PMID- 7823221
TI  - Quantitative measurement of vibratory perception threshold using a new vibrometer
      TM-31A.
AB  - The need for standardization and validation of quantitative tests for vibratory
      sensitivity has been increasingly recognized. Conventional vibrometers have been
      of limited use for the assessment of vibratory perception threshold (VPT) due to
      wide intraindividual variations. This study describes the determination of VPT
      for the medial malleolus (MM), the styloid process of the radius (SPR), and the
      pulp of the index finger (PIF) in normal subjects, using a new vibrometer, the TM
      31A. This apparatus expresses results in terms of actual vibration amplitude and
      has a feedback mechanism that avoids damping of the stimulator in tissue.
      Repeated VPT measurements revealed good reproducibility of the test. The intraday
      and day-to-day variations of VPT were fairly small. VPT was found to differ
      significantly among sites (MM > SPR > PIF). The distribution in MM was
      substantially log-normal, whereas the SPR and PIF were normal. VPT values on each
      site correlated with advancing age, especially on the MM. It is concluded that TM
      31A provides a reliable and valid assessment of VPT and contributes to the
      standardization of VPT testing.

PMID- 7823222
TI  - Reliability and validity of a newly developed test of physical work performance.
AB  - This study examined the interrater reliability and validity of a newly developed
      test of physical work abilities, the Physical Work Performance Evaluation. Eleven
      physical therapists were trained to administer and score this evaluation. From
      this group, two therapists at a time simultaneously and independently evaluated
      50 patients with musculoskeletal disorders as they performed the tasks of the
      Physical Work Performance Evaluation. At the conclusion of the evaluation, each
      therapist determined the safe level of physical work for each patient. A
      comparison of the two independent evaluations was used to determine reliability.
      To determine validity, the predicted level of work was compared with the actual
      level of work. Kappa coefficient between the two therapists on the level of work
      was .83. Spearman rho correlations between the predicted and actual levels of
      work ranged from .41 to .55. Only 14 to 18% were working above the level
      predicted by the Physical Work Performance Evaluation. These results indicate
      high interrater reliability. Given the lack of a perfect standard for validity
      comparisons, these results also provide evidence in support of convergent
      validity. The test can be used in making decisions regarding return to work after
      injury, preemployment placement, and vocational exploration.

PMID- 7823223
TI  - Prior capacity of patients lacking decision making ability early in
      hospitalization: implications for advance directive administration. The SUPPORT
      Investigators. Study to Understand Prognoses and Preferences for Outcomes and
      Risks of Treatments.
AB  - OBJECTIVE: To investigate the appropriateness of hospitalization as the time to
      elicit patients' medical care preferences, the authors evaluated the capability
      of seriously ill patients to participate in decision making early in
      hospitalization and their decision making capacity two weeks before hospital
      entry. DESIGN: Cross-sectional study with retrospective evaluation of
      preadmission decision making capacity. SETTING: Five acute care teaching
      hospitals. PATIENTS: Four thousand three hundred one acutely ill hospitalized
      adults meeting predetermined severity of illness criteria in nine specific
      disease categories. MEASUREMENTS: Surrogate decision makers' estimates of the
      prior mental capacities of patients unable to be interviewed early in
      hospitalization about care preferences due to intubation, coma, or cognitive
      impairment. Comparison of the demographics, degrees of sickness at admission, and
      outcomes of interviewable vs noninterviewable patients. MAIN RESULTS: Forty
      percent of the patients were not interviewable concerning preferences. Of these,
      83% could have participated in treatment decisions two weeks prior to
      hospitalization. The patients who were not interviewable were more acutely ill,
      had less chronic disease, and were more likely to die during hospitalization than
      the interviewable patients. CONCLUSIONS: Many acutely ill patients likely to die
      in the hospital lost their ability to make medical care decisions around the time
      of hospital admission. Preferences for care and advance directives should be
      discussed in the outpatient setting or very early in hospital admission.

PMID- 7823225
TI  - Screening with the Alcohol use Disorders Identification Test (AUDIT) in an inner
      city population.
AB  - OBJECTIVES: 1) To determine the operating characteristics of the Alcohol Use
      Disorders Identification Test (AUDIT) in an inner-city population and 2) to
      compare AUDIT performance with physician recognition of alcohol-related problems.
      DESIGN: New patients were administered a health habits questionnaire, which
      included the AUDIT and the alcohol portion of the Structured Clinical Interview
      for DSM-III-R (used as the "gold standard" for alcohol abuse or dependence). The
      findings were compared with physician recognition based on chart review. SETTING:
      Inner-city general medicine clinic staffed by resident physicians with faculty
      supervision. PATIENTS/PARTICIPANTS: Consecutive new patients over a ten-week
      period. Of 166 consecutive new patients, 23 were not contacted, 17 refused to
      participate, two were excluded for gross cognitive deficits, and 124 completed
      the study. RESULTS: Of the 124 patients, 41 (33%) met criteria for past or
      present alcohol abuse or dependence. The AUDIT correctly identified 26/27
      (sensitivity of 96%) of patients with current problems and 0/14 of patients with
      past problems only. Physician rates of recognition of current and past alcohol
      related problems based on chart review were 12/27 (sensitivity of 44%) and 1/14
      (7%), respectively. The specificities of both the AUDIT and physician recognition
      were high, 96% and 99%, respectively. CONCLUSIONS: 1) Alcohol-related problems
      were common in this setting, 2) The AUDIT had a high sensitivity and a high
      specificity for detection of current alcohol problems in this setting, but it
      failed to detect patients with only past histories of alcohol problems. 3) The
      AUDIT performed significantly better than did the physicians in detecting alcohol
      problems. 4) The addition of an assessment of past alcohol use to supplement
      information from the AUDIT would appear to represent a promising screening
      strategy worthy of further investigation.

PMID- 7823224
TI  - Measuring physician attitudes toward cost, uncertainty, malpractice, and
      utilization review.
AB  - OBJECTIVE: To develop a reliable measure of physician attitudes postulated to
      influence resource utilization. DESIGN: Statements related to attitudes that may
      influence resource use were culled from the literature and informal discussions
      with physicians. SETTING: Academic medical center. PARTICIPANTS: All faculty and
      housestaff in internal medicine, pediatrics, family medicine, and surgery at an
      academic medical center were surveyed. The response rate was 59% (n = 428).
      RESULTS: Exploratory factor analysis of all internal medicine surveys revealed
      four prominent domains. These closely corresponded with our a-priori hypothesized
      domains and were interpreted as cost-consciousness, discomfort with uncertainty,
      fear of malpractice, and annoyance with utilization review. A replication of the
      analysis using 25 survey items and conducted on the remainder of the data
      (surgeons, pediatricians, and family practitioners) revealed a similar four
      factor solution. Scales were constructed for each of the four domains. Cronbach's
      alpha ranged from 0.66 to 0.88. Discomfort from uncertainty and fear of
      malpractice were moderately correlated (r = 0.42); other scale-scale correlations
      were modest. Of the four attitude measures, only cost-consciousness was
      associated with lower self-estimates of resource use. Both annoyance with
      utilization review and fear of malpractice increased as the proportion of time
      spent in patient care increased. CONCLUSIONS: Although various physician
      attitudes and beliefs have been hypothesized to influence health services
      resource use, reliable and valid measures for most of these have not been
      developed. The authors developed a 19-item survey instrument designed to measure
      these attitudes reliably. The four scales developed in this study may help
      identify physician attitudes that are important determinants of physician
      decision making and help foster a better understanding of physicians' reactions
      and acculturation to different practice environments.

PMID- 7823226
TI  - After-hours telephone calls to general and subspecialty internists: an
      observational study.
AB  - OBJECTIVE: To study the after-hours telephone calls received by practicing
      general and subspecialty internists. DESIGN: Observational study. SETTING: Forty
      four internal medicine private practices in Long Island, New York, consisting of
      70 physicians (31 general internists, 39 internists with subspecialty training).
      PATIENTS/PARTICIPANTS: All calls received by an answering service after office
      hours with the caller requesting to speak to one of the physicians in the study.
      Of the 8,444 total calls, 2,950 were to generalists and 5,494 were to
      subspecialists. MEASUREMENTS AND MAIN RESULTS: For both groups, most calls came
      from patients (46.3%), followed by physicians (26.0%), then hospitals (22.2%).
      For patient calls to the generalists, those concerning infectious disease
      (15.4%), nonspecific symptoms (11.1%), medication-related questions (9.7%), and
      gastrointestinal (GI) complaints (9.4%) were the most common. For those calls to
      the specialists, GI (14.2%), infectious disease (10.9%), medication-related
      (10.0%), and nonspecific symptom (9.0%) complaints represented the most common
      patient calls. Although GI and cardiology specialists received proportionally
      more patient calls related to their specialities, the specialty group, like the
      generalist group, received calls in all the major areas of internal medicine.
      Patient calls for problems well outside the traditional scope of internal
      medicine accounted for 2.9% of the calls to the generalists and 1.9% of the calls
      to the specialists. About 44% of the patient calls to both groups were for
      potentially serious problems. After 11:00 PM both groups saw a decrease in the
      proportions of minor and trivial calls. CONCLUSIONS: These observations support
      the concept of broadly based medical training for both internal medicine
      generalists and subspecialist in preparation for the variety of telephone calls
      they will deal with after office hours. Practitioners should take steps to reduce
      the high number of medication-related patient calls.

PMID- 7823227
TI  - Should physicians screen for oral disease? A physical examination study of the
      oral cavity.
AB  - OBJECTIVE: To assess how well primary care clinicians select patients needing
      early referral to a dentist based on an oral cavity examination. DESIGN:
      Prospective comparison of the screening oral cavity examinations performed by
      primary care clinicians with that performed by a dentist. SETTING: General
      medicine clinic and dental clinic of a Veterans Affairs Medical Center. PATIENTS:
      A sample of 86 consecutive patients attending regularly scheduled appointments in
      a primary care medical clinic. MEASURES: Each patient was examined independently
      by two primary care clinicians and then one dentist. History and physical
      findings, clinical impression, and plan based on the oral cavity examination were
      recorded. The reference standard was the examination by a dentist blinded to the
      patient's history. RESULTS: The prevalences of lesions suspicious for
      premalignancy, periodontal disease, calculus, and caries were 23%, 37%, 54%, and
      18%, respectively. When the primary care clinicians noticed a lesion suspicious
      for premalignancy, the likelihood that such a lesion was present increased
      significantly (LR+ = 2.7 to 6.6). However, a normal examination by the primary
      care clinicians did not significantly lower the likelihood of a premalignant
      lesion (LR- = 0.7 to 0.8). The primary care clinicians were more efficient at
      evaluating dental and gingival conditions (LR+ = 2.7 to 5.8, LR- = 0.2 to 0.7).
      CONCLUSIONS: Screening for oral disease by primary care clinicians is justified
      but should not replace routine screening by dentists.

PMID- 7823228
TI  - Separating the wheat from the chaff: identifying fallacies in pharmaceutical
      promotion.

PMID- 7823229
TI  - Strategies for counseling depressed patients by primary care physicians.

PMID- 7823230
TI  - Using health-related quality-of-life information: clinical encounters, clinical
      trials, and health policy.

PMID- 7823232
TI  - Functional disability screening of ambulatory patients: a randomized controlled
      trial in a hospital-based group practice.
AB  - The authors conducted a randomized controlled trial of functional disability
      screening in a hospital-based internal medicine group practice. They assigned 60
      physicians and 497 of their patients to either an experimental or a control
      group. Every four months the patients in both groups completed a self
      administered questionnaire measuring physical, psychological, and social
      function. The experimental group physicians received reports summarizing their
      patients' responses; the control group physicians received no report. At the end
      of one year the authors found no significant difference between the patients of
      the experimental and control group physicians on any measure of functional
      status. Functional disability screening alone does not improve patient function.

PMID- 7823231
TI  - Diagnosis and treatment of Parkinson's disease in the elderly.

PMID- 7823234
TI  - An academic career: is it possible part-time?

PMID- 7823233
TI  - Advance planning for advance directives.

PMID- 7823235
TI  - Plantar ulcers as the only clinical manifestation of polyarteritis nodosa.

PMID- 7823236
TI  - [Acoustic analysis of certain consonants using a computed model of the peripheral
      auditory system].
AB  - Stop consonants [p], [t], [k] and a fricative [s] were acoustically analyzed
      using a computed model of the peripheral auditory system in 12 normal subjects
      and 12 patients with tumors of the tongue who had undergone surgical resection
      and reconstruction. The model is a combination of the cochlear model that
      consists of 28 FIR filters (Delgutte) and the inner hair-cell/auditory nerve
      synapse model (Meddis), with some modification. It simulates firing of the
      auditory nerve in every channel related to the FIR filters in response to an
      input voice signal. Phonetic characteristics of the tested consonants were more
      clearly visualized by observing firing patterns and voice onset time (VOT) using
      this auditory model than with use of the conventional soundspectrogram. In
      patients with tumors of the tongue, the degree of distorted articulation and the
      area of surgical resection were significantly related to obscurity of the
      phonetic characteristics of the stop consonants [t] and [k]. Acoustic analysis
      using this auditory model may serve as a useful tool for voice analysis in
      research and in the clinical field.

PMID- 7823237
TI  - [Testing of synthetic vowels in patients with 22 channel cochlear implant].
AB  - In the 22 multi-channel cochlear implant system, F0 information determines the
      frequency of electrical stimulation, and F1 and F2 information determine the
      number of stimulating electrodes. We performed tests using synthetic vowels on 16
      patients who had undergone 22 channel cochlear implant surgery and 6 months'
      speech rehabilitation. Information transmission rates were calculated to analyze
      the response pattern. As a result, 1) the vowel recognition ability of patients
      with cochlear implant surgery correlated with the number of electrodes being
      used. 2) The value of vowel confusion decreased so as to be separated by a pair
      of stimulating electrodes, and the confusion in F1 information was regarded to be
      less than that for F2 information.

PMID- 7823238
TI  - [Sex hormones in fibrous dysplasia of the facial bone--an immunohistological
      study].
AB  - Fibrous dysplasia of the facial bones frequently occurs in the maxilla around the
      time of puberty and becomes inactive when skeletal growth is completed. A case of
      fibrous dysplasia of the maxilla and sphenoidal-temporal bone in a 19 year-old
      male was studied, in terms of the presence of estradiol, testosterone and
      dihydrotestosterone, using the peroxidase-antiperoxidase method. This case
      underwent partial surgical resection, for cosmetic deformity, of the maxillary
      tumor which, however, relapsed to preoperative size within three weeks. Estradiol
      and testosterone were strongly positive and dihydrotestosterone was slightly
      positive in the tumor cells. Sex hormones were apparently present in the tumor
      cells and exerted a strong influence on the growth of the fibrous dysplasia.

PMID- 7823239
TI  - [Cochlear implants in children].
AB  - A multichannel cochlear implant was performed in 8 children, and the following
      results were obtained. The surgical procedures were not as difficult as in
      adults, and there were few postoperative complications. The results of testing
      postoperative speech comprehension ability were examined in three children whose
      course was followed for more than one year postoperatively. Some patients had
      good speech comprehension ability postoperatively, and we expect to continue
      performing cochlear implant in children. Postoperative rehabilitation takes
      longer. The cooperation of physicians, audiologists, speech therapists, school
      teachers and family members is essential, and establishing a cochlear implant
      center for children would be desirable.

PMID- 7823240
TI  - [Cochlear implants for adult prelingually deaf patients].
AB  - We have performed cochlear implants on 6 adult prelingually deaf patients and
      obtained the following results. 1) The speech comprehension ability of the adult
      prelingually deaf patients was poorer than in postlingually deaf patients, but
      some patients showed better results than expected. 2) The adult prelingually deaf
      patients required a longer period of rehabilitation than the postlingually deaf
      patients. There were considerable variations in performance among the adult
      prelingually deaf patients.

PMID- 7823241
TI  - [A correlation between metastasis and histopathological differentiation in
      patients with carcinoma of the nasal cavity and paranasal sinuses].
AB  - The aim of this retrospective study was to investigate a correlation between
      histopathological differentiation and metastasis in patients with carcinoma of
      the nasal cavity and paranasal sinuses to improve the survival. Between 1984 and
      1992, 52 cases of sino-nasal malignant tumors were treated at Kagawa Medical
      School Hospital. Squamous cell carcinoma was evaluated in 29 patients and
      undifferentiated carcinoma in five patients. Treatment in most cases consisted of
      radiotherapy, 50 Gy/25 fr/5 weeks, continuous intra-arterial infusion of 5-FU
      2000 mg/4 weeks, and an extensive Denker's operation 2-3 weeks after the
      completion of radiotherapy. The 5-year survival rate was 53%, and the local
      control rate was 82%. Patients died of local failure (six), distant metastases
      (six), lymph node metastases (one) and other causes (three). Twenty-eight
      patients with local control were classified into G1-2 (well- and moderately
      differentiated) and G3-4 (poorly-differentiated and undifferentiated) groups.
      Lymph node metastasis was unrelated to the degree of differentiation, but distant
      metastasis was significantly correlated to the degree of differentiation (P =
      0.014). The 5-year survival rates in lymph node metastasis (n = 7), non-lymph
      node metastasis (n = 21), distant metastasis (n = 7), non-distant metastasis (n =
      21), and the G1-2 (n = 17) group and the G3-4 group (n = 11) with local control
      were 57%, 63%, 14%, 78% (P = 0.002), 72% and 44% (P = 0.0384), respectively. The
      results of combination therapy were poor in patients with poorly-differentiated
      or undifferentiated carcinoma because of distant metastasis, and adjuvant
      chemotherapy may be necessary in such patients to prevent distant metastasis.

PMID- 7823242
TI  - [Assessment of the volume of the mastoid air cell system using digital image
      processing].
AB  - There has been a great deal of controversy concerning the development of
      pneumatization in the temporal bone. Many reports on the size of the mastoid air
      cell system have been discussed a planimetric X-ray method, however, there have
      been no techniques for direct volume measurement based on high-resolution
      computed tomography (CT). Discussion of the relationship between ear disease and
      pneumatization of the temporal bone requires three-dimensional measurement of the
      temporal bone in vivo. Recently, we developed such a technique by using digital
      image processing to measure the volume of the mastoid air cell system. With this
      technique, only the air cells and tympanic cavity, with a grey scale level
      similar to air outside the skull were easily selected on the CT films. Then,
      after image processing called "thresholding", only the areas and volumes of these
      extracted pneumatized parts were calculated. The volumes of the pneumatized parts
      of the temporal bone were calculated separately as partial volumes divided by
      several CT planes. The sum of the partial volumes was calculated as the total
      volume of the aerated cavity. This technique also made it possible to reconstruct
      a three-dimensional (3D) model of the air cell system for visual presentation. CT
      images of 43 normal temporal bones were analyzed. The average volume temporal
      bone pneumatization (including air cells and tympanic cavity) was about 6ml.
      There were no differences between pneumatization on the two sides in either sex.
      Comparisons of partial volumes of pneumatization in the temporal bone revealed
      that the volumes of portions including the tympanic cavity and its surrounding
      air cells and those of the antrum and its surrounding air cells were larger than
      those of other portions. 3D models of the air cell system revealed a variety of
      shapes. These findings indicated that this technique is not only useful for
      quantitative analyses but for easy subjective morphological analyses.

PMID- 7823243
TI  - [A case of revision of a cochlear implant].
AB  - The patient was a 41-year-old man who lost his hearing on the left at 7 years of
      age and on the right at 34 years of age due to meningitis. At 35 years of age a
      single-channel cochlear implant, 3M/House design, was implanted. Five years after
      the initial operation, the single-channel prosthesis was replaced by a
      multichannel device (Cochlear Corp.) because of the patients earnest wish to
      obtain better hearing. Explanation of the short electrode of the single-channel
      device was easy, but reimplantation of the longer electrode of multichannel
      device was somewhat difficult, probably because of the presence of the peri
      implant fibro-osseous cuff in the Scala tympani. Single-channel and those of the
      multichannel speech data were compared in relation to performance in the same
      individual. The reimplanted multichannel device was equivalent to or outperformed
      the original 3M prosthesis. The patient preferred the hearing afforded by the
      multichannel device.

PMID- 7823244
TI  - [Electrocochleographic study of acute low-tone sensorineural deafness].
AB  - We assessed 53 patients with acute low-tone sensorineural deafness (LTSD) over
      the past 10 years using the transtympanic-electrode technique of
      electrocochleography. The audiometric diagnostic criteria were as follows:
      Average hearing level at the lower two frequencies (250, 500Hz) greater than 30
      dB, and of the higher three frequencies (2, 4, 8kHz) less than 20 dB. Patients
      were divided into three groups on the basis of their electrocochleographic
      findings; 33 cases of the endolymphatic hydrops type, 17 cases of the hair cell
      damage type and 3 cases of the neural damage type. The outcome of these patients
      was assessed together their electrocochleographic findings. The results obtained
      were as follows: 1) Most of the improved cases were of the endolymphatic hydrops
      type and in females in their twenties. All of the improved cases showed high AP
      and -SP amplitude, but not dominant -SP, and exhibited slight prolonged AP
      latency. Satisfactory CM responses at 500 Hz were also found. 2) Most of the hair
      cell damage type exhibited no change, and some unrecovered cases of the
      endolymphatic hydrops type progressed to Meniere's disease.

PMID- 7823245
TI  - [Analysis of lymphocyte subsets in human lingual tonsils].
AB  - Lymphocytes in the lingual tonsil were analyzed using monoclonal antibodies to
      cell surface markers. Immunohistologic staining of lingual tonsillar tissue
      showed localization of the various lymphocyte subsets in the germinal center,
      mantle zone, and inter-follicular area. Populations of lymphocyte subsets, i.e.,
      T cells, B cells, CD4 positive cells, CD8 positive cells, alpha beta T-cells,
      gamma delta T-cells, and NK cells were assessed by laser flow cytometry analysis,
      and we compared the following tissues: peripheral blood, lingual tonsils,
      palatine tonsils, and pharyngeal tonsils (adenoids).

PMID- 7823246
TI  - The role of Epstein-Barr virus in the pathogenesis of Hodgkin's disease.

PMID- 7823247
TI  - Detection of T-cell receptor beta chain mRNA in frozen and paraffin-embedded
      biopsy tissue using digoxigenin-labelled oligonucleotide probes in situ.
AB  - In situ hybridization techniques using a cocktail of digoxigenin-labelled T-cell
      receptor (TcR) constant (C) region beta oligonucleotide probes were used to
      detect TcR beta mRNA in frozen and paraffin-embedded tissue sections. The
      specificity of the C beta cocktail was confirmed by Northern blot analysis. The
      TcR C beta cocktail successfully hybridized to T cells in frozen and paraffin
      embedded tissue obtained from patients with inflammatory arthropathies, B- and T
      cell non-Hodgkin's lymphoma (NHL), and reactive tonsillitis, and showed staining
      patterns comparable to those obtained by conventional immunohistological
      detection of T cells. This is the first report of in situ studies using labelled
      TcR C beta oligonucleotide probes and may indicate the feasibility of
      investigating clonal T-cell populations using digoxigenin-labelled clonospecific
      probes in clinical samples in situ.

PMID- 7823248
TI  - p53 expression, mutation, and allelic deletion in ovarian cancer.
AB  - The aim of this investigation was to study the prevalence of p53 gene mutations
      and allelic deletions in ovarian cancer and the relationship between these events
      and p53 expression. Genomic p53 was amplified by the polymerase chain reaction
      (PCR) from paraffin-embedded sections of tumour and non-tumour tissue. Exons 5-9
      were screened for mutation using non-isotopic single-strand conformation
      polymorphism (SSCP) analysis. Allelic deletions at a sequence polymorphism in
      exon 4 were studied for loss of heterozygosity (LOH) by restriction analysis and
      by SSCP. p53 expression was detected by immunohistochemistry with the p53
      antibodies CM1 and Do7. Of 44 cases, ten (23 per cent), including a mucinous
      tumour of low malignant potential, showed mutations. There was a statistically
      significant correlation between p53 mutation and expression (P < 0.01) but seven
      cases showed discordance. Of 18 informative cases, eight (44 per cent)
      demonstrated LOH. Mutations were identified in three of the informative cases,
      two of which also had LOH. The remaining case showed mutations in two amplicons.
      p53 dysfunction, as indicated by mutation, deletion, or increased expression, is
      common in ovarian cancer. There is an association between these molecular events
      but the exact mechanisms of p53 inactivation remain to be elucidated.

PMID- 7823249
TI  - Racial variation in the O-acetylation phenotype of human colonic mucosa.
AB  - O-acetylated and non-O-acetylated sialoglycoproteins can be distinguished by the
      mPAS (mild periodic acid-Schiff) histochemical technique. Individual adults show
      one of three different patterns of staining of large intestinal mucosa: uniformly
      mPAS-positive, uniformly mPAS-negative, or mPAS-negative with scattered mPAS
      positive crypts. To test our hypothesis that these variations are the result of a
      single autosomal gene (oat) polymorphism, we have studied the frequency of the
      three patterns of staining in a total of 435 adult colon specimens from six
      geographically separate populations: British, South African blacks, Icelanders,
      Japanese, Hong Kong Chinese, and Bahrainis. The distribution of the three types
      of staining fell into two groups. In Japanese and Chinese, uniformly mPAS
      positive cases were much more frequent than uniformly mPAS-negative cases; this
      distribution differed significantly (chi 2, P < 0.001) from that in non-Sino
      Japanese, where the uniformly mPAS-positive phenotype was much less frequently
      found than the uniformly mPAS-negative phenotype. In neither of the groups did
      the frequency of the three phenotypes differ significantly from that predicted
      for a single gene polymorphism by the Hardy-Weinberg law. The variation in
      staining patterns between populations is consistent with variation in frequency
      of a single polymorphic autosomal gene (oat) controlling O-acetylation of sialic
      acid, probably by an O-acetyl transferase enzyme. Loss of function mutation in
      the high acetylator gene (oata) in a colonic crypt stem cell in heterozygous
      individuals would account for the scattered discordant crypts. Gene frequencies
      for a variety of enzymes differ between the Sino-Japanese and non-Sino-Japanese
      races.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7823250
TI  - Human colonic stem cell mutation frequency with and without irradiation.
AB  - Mild periodic acid-Schiff (mPAS) staining distinguishes O-acetylated from non-O
      acetylated sialoglycoproteins. In human colonic mucosa, individuals possess one
      of three phenotypes: uniformly mPAS-positive (non-O-acetylated), uniformly mPAS
      negative (O-acetylated), and negative with infrequent scattered positive crypts.
      This is due to a polymorphism in a single autosomal gene (oat). Discordant crypts
      have not been found in children's colons, suggesting that they result from
      somatic mutation in heterozygous individuals. We now present evidence to confirm
      this based on a study of radiation-induced changes. Comparison of mPAS staining
      of large intestinal mucosa from patients given radiation 4 weeks before surgery
      for carcinoma of the rectum with matched controls receiving surgery alone showed
      a similar phenotype distribution, but information irradiated patients showed an
      increased frequency of discordant crypts (irradiated vs. non-irradiated 14.5 +/-
      8.2 x 10(-4) vs. 6.1 +/- 4.2 x 10(-4)). When these were classified as wholly or
      partially involved by the aberrant phenotype, the increase was most marked in
      partially involved crypts (7.5 +/- 4.5 x 10(-4) vs. 0.3 +/- 0.5 x 10(-4), Mann
      Whitney U, P < 0.005). Two patients receiving radiotherapy many years before
      colectomy showed a very high total discordant crypt frequency but relatively few
      partially affected crypts. Studies of somatic mutation in colonic or small
      intestinal crypts following a single dose of mutagen in mice have shown early
      partial crypt involvement by the mutated phenotype and later complete crypt
      involvement.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7823251
TI  - HLA-DR antigen expression and lymphocyte subsets in transitional cell carcinoma
      of the urinary bladder. An immunohistological study on frozen sections.
AB  - Lymphocyte subpopulations (B cells, CD4, CD8), interleukin-20 receptors (IL-2),
      monocytes/macrophages (Leu M5), and HLA-DR antigen expression were studied
      immunohistochemically on frozen sections from 38 bladder cancer specimens. T
      cells predominated over B cells in all tumours. CD4-positive lymphocytes
      predominated over CD8 in the stroma (CD4/CD8: 1.35/l), while in epithelial tumour
      cells CD8 was the prominent subpopulation (CD8/CD4: 1.75/l). Aberrant HLA-DR
      expression was found in 21.05 per cent of bladder tumours. A strong correlation
      between CD4 and CD8 population densities and macrophages with the other
      subpopulations was noticed. In HLA-DR-positive tumours, there was no correlation
      of the percentage of positive cells with CD4- and CD8-positive lymphocyte
      populations. Various parameters including IL-2 receptors, B cells, CD8- and CD4
      positive cells, and macrophages did not differ significantly between the groups
      of tumours expressing and not expressing HLA-DR antigen. There were no
      statistically significant differences in the population densities of B cells, CD8
      or CD4-positive cells, IL-2 receptor, monocytes/macrophages, and HLA-DR antigen
      expression among various clinicopathological parameters, including growth
      pattern, histological grade and clinical stage or patient's age and sex. These
      findings suggest that in transitional cell carcinoma of the urinary bladder, HLA
      DR antigen expression is independent of lymphocyte subpopulations. It is
      therefore possible that HLA-DR expression by tumour cells reflect the existence
      of separate HLA-DR-positive or HLA-DR-negative tumour clones.

PMID- 7823252
TI  - Detection of the c-met proto-oncogene product in normal skin and tumours of
      melanocytic origin.
AB  - The proto-oncogene c-met product (c-MET) is a receptor tyrosine kinase and
      functions as a receptor for hepatocyte growth factor (HGF). Although the function
      of c-MET has yet to be fully clarified, HGF stimulates the phosphorylation of
      tyrosyl residues on c-MET and triggers the signal transduction pathways,
      resulting in a contribution to the malignant progression of melanonocytes with
      synergic factors such as basic fibroblast growth factor and mast cell growth
      factor. Using immunohistochemical methods, we have studied the localization of c
      MET in normal skin and various melanocytic tumours. c-MET was detected in
      keratinocytes, melanocytes, sebaceous cells, and other cells of the skin. In
      particular, basal melanocytes almost always showed nuclear labelling. Melanocytic
      naevi generally revealed predominantly nuclear staining of cells in the
      epidermis, whereas only a few cases showed a distinct cytoplasmic localization of
      c-MET in dermal naevus cells. The distribution pattern of c-MET in melanoma cells
      was basically similar to that of benign lesions, although the numbers tested were
      small. Cultured human melanoma cells also showed predominantly nuclear labelling,
      but were unresponsive to exogenous c-MET ligand HGF. Treatment with the
      glucosidase inhibitor castanospermine caused accumulation of protein at 220 kD,
      without diminishing the amount of normally-processed 190-kD c-MET. Although there
      was no significant difference in c-MET distribution between benign and malignant
      melanocytic lesions, it is suggested that malignant transformation of melanocytes
      may be associated with loss of response to HGF or other growth-regulating
      factors.

PMID- 7823253
TI  - Proliferative activity in benign and neoplastic prostatic epithelium.
AB  - The increasing availability of means for the early detection of prostatic cancer
      has brought under scrutiny the criteria used for prognosis and emphasized our
      limitations in understanding what determines the rate of progression in these
      cancers. The rate of cancer cell proliferation has been under intense
      investigation, which, however, has yielded conflicting results. In this study we
      evaluated the proliferative activity of benign and neoplastic prostatic
      epithelium, using various existing methodologies. We first analysed the
      variability introduced by the methodological approach and then attempted to
      demonstrate whether determination of the proliferative capacity had any clinical
      consequence that complemented the histological grading. Tissue samples from
      patients, 88 with cancer and 46 with benign prostatic pathology, were studied
      using in vitro bromodeoxyuridine (BrdU) incorporation as well as Ki67 and the
      proliferating cell nuclear antigen (PCNA) to estimate the proliferative activity.
      Increased proliferation was found consistently in inflammation and metaplasia,
      but not in hyperplasia. In contrast, cancers showed marked variability. Although
      average proliferation indices increased with grade, there was a wide scatter of
      values. Correlation was stronger with stage, but also depended on the
      methodology. Bromodeoxyuridine indices over 10 per mile had a positive predictive
      value of 79 per cent for cancers extending beyond the prostatic capsule and may
      prove particularly helpful for evaluating patients with grade 7 cancer. This
      observation is significant, since grade 7 cancers are the most frequent and the
      least predictable.

PMID- 7823254
TI  - The expression of alpha B-crystallin in epithelial tumours: a useful tumour
      marker?
AB  - Alpha B-crystallin is a lens protein showing homology with small heat-shock
      proteins. We have previously demonstrated its expression in non-lenticular normal
      and diseased human tissues by immunostaining with a polyclonal antibody. In view
      of the expression seen in normal renal tubular epithelium, we have assessed the
      immunoreactivity of a variety of epithelial tumours, to determine the usefulness
      of alpha B-crystallin as a specific renal tumour marker. Carcinomas arising from
      tissues which normally express alpha B-crystallin, such as colo-rectal and
      thyroid carcinomas, showed a varying pattern and degree of immunoreactivity. The
      most consistently positive tumours, however, with typically strong cytoplasmic
      and cell membrane staining, were renal cell carcinomas, 90 per cent of which
      showed positive immunoreactivity. This pattern of staining, while not absolutely
      specific, is a useful aid to the diagnosis of renal carcinoma. When a metastic
      deposit or a small biopsy is being assessed, anti-alpha B-crystallin may be
      included in a panel of antibodies, the pattern of staining of which may direct
      the search for the primary site of the tumour.

PMID- 7823255
TI  - Hitherto unrecognized arterioles within hepatocellular carcinoma.
AB  - The distribution of blood vessels in human hepatocellular carcinoma was studied
      with the anti-a-smooth muscle actin monoclonal antibody by light and electron
      microscopy, and with morphometric analysis. a-Smooth muscle actin-positive
      arterioles were never observed in lobules or pseudolobules of non-cancerous
      areas, but were frequently seen within hepatocellular carcinomas. Morphometric
      analysis revealed that most of these arterioles measured between 10 and 25
      microns in diameter. The morphology of intratumoural arterioles differed
      considerably from that of conventional arteries in the portal tracts of the non
      cancerous area. The presence of abundant intratumoural arterioles can explain the
      angiographic hypervascularity of hepatocellular carcinoma and provides a
      pathological basis for its susceptibility to hypoxia and for arterial
      embolization as a therapeutic strategy.

PMID- 7823256
TI  - Evaluation of a simple method to assess fetal well-being in antenatal clinic.
AB  - To study the feasibility of assessing fetal heart rate (FHR) acceleration by a
      fetal doptone and fetal movements (FM) as perceived by the mother and observed by
      the attendant in response to a vibroacoustic stimulus. Baseline FHR and it's
      response during the first minute after vibroacoustic stimulation was observed by
      a fetal doptone with a digital display on 317 occasions in 201 pregnancies (81.4%
      of whom were high risk) during antenatal visits in the third trimester. Fetal
      movements in response to the stimulus were recorded by the mother and the
      examiner. FHR increased 15 beats greater than the baseline rate for > 15 secs in
      269 of the tests (83.4%), and fetal movements were observed by the mother in 301
      (94.9%) of the tests. A FHR increase in > or = 15 bpm together with maternal and
      examiner perceived fetal movements were observed in 250 tests (81.7%). Good
      correlation was seen between the mother and the examiner (97.8%) of the
      observation of presence or absence of fetal movements to the vibroacoustic
      stimulus. One of the three parameters i.e. increase in FHR > or = 15 beats > or =
      15 secs or perception of fetal movement either by the mother or the observer were
      present in 98.1% of the tests. If it could be considered that one of these three
      signs are indicative of good fetal health further investigations of fetal well
      being would be needed in only 1.9%. The fetal outcome was uneventful in all
      pregnancies studied.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7823257
TI  - Renal function and urinary urokinase in hypertensive and diabetic pregnancies.
AB  - Urokinase (u-PA) dissolves and removes fibrin deposits in the renal secretory
      pathways in various renal diseases. During pregnancy nephropathy creates a
      problem in preeclampsia and diabetes, but the underlying mechanism of glomerular
      damage is different. Preeclamptic nephropathy is characterized as 'glomerular
      endotheliosis' with hypertrophy of the intracapillary cells, and diabetic
      nephropathy as 'glomerulosclerosis' with hyaline deposits. The role of fibrin
      deposition for the etiology of renal damage in preeclampsia is controversial.
      Changes of the urinary secretion of u-PA may reflect the type of glomerular
      damage. Our hypotheses were that renal insufficiency is associated with a low u
      PA activity in both conditions, and that severe disease is parallel to declining
      concentrations of u-PA. We compared the glomerular filtration rate, S-Creatinine
      and S-Urate with urinary u-PA excretion in 24 hypertensive and 20 diabetic
      pregnant women. In diabetic patients, a low u-PA concentrations was associated
      with an impaired renal function. In hypertensive pregnancy, the u-PA excretion
      did not reflect the severity of the hypertensive disease or renal function. No
      association was found between u-PA excretion and renal function post partum in
      any group. We conclude that renal urokinase activity plays a role for renal
      function in diabetic but not in hypertensive pregnancy.

PMID- 7823258
TI  - Cord blood levels of calcium-regulating hormones and osteocalcin in premature
      infants.
AB  - We measured cord blood levels of calcium-regulating hormones and osteocalcin in
      34 premature infants of various gestational ages. 1,25(OH)2D levels were low in
      mid-gestation and increased with advancing gestation. Parathyroid hormone levels
      were low, and calcitonin levels were high in mid-gestation. Both of them declined
      with advancing gestation. Osteocalcin levels were high in mid-gestation. They
      increased from 22 weeks through 27 weeks of gestational age, and decreased
      thereafter. Circulating osteocalcin is considered as a clinical marker of bone
      turnover. However, cord blood osteocalcin decreased between 27 and 36 weeks of
      gestation during which period calcium accumulation by the fetus increases.
      Therefore, cord blood osteocalcin does not appear to reflect fetal bone
      formation.

PMID- 7823259
TI  - Problems in the clinical use of intrapartum fetal ECG monitoring.
AB  - Commercial machines are now available to monitor the fetal electrocardiograph in
      labour (Cinventa, Sweden). We report our experience of the first one hundred
      women we monitored by this method. They were divided into five groups dictated by
      the change in the fetal scalp electrode used for monitoring and the changes made
      in the computer software used for signal processing. There were progressive
      significant improvements in the ability of the system to produce a continuous
      heart rate trace such that it became acceptable for routine fetal monitoring. The
      quality of the electrocardiogram improved to 50% of the 'check ECG complexes'
      being printed accurately. Electrical signal distortion causing baseline wander is
      however the significant remaining problem. On-line analysis of the T/QRS ratio
      improved very significantly from 36% to 84% of the monitoring time. There were no
      significant improvements in the recordings made in the second stage, which
      remained poorer in quality and reliability in all groups. As well as changes in
      the computer software, the use of a single helix electrode and practical
      experience contributed to the improvements.

PMID- 7823260
TI  - Low-dose aspirin to pregnant women: single dose pharmacokinetics and influence of
      short term treatment on bleeding time.
AB  - Single dose pharmacokinetics of 75 mg aspirin was investigated in two groups of
      ten women with clinically normal pregnancies. Eleven non-pregnant subjects in the
      same age were controls. In group A, gestational age was 27-30 completed weeks,
      and in group B, 36-39 weeks. Venous blood samples were taken before and up to 240
      minutes after the intake of the aspirin. Liquid chromatographic assays for
      acetylsalicylic acid (ASA) and its metabolite, salicylic acid (SA), was
      performed. The pharmacokinetics of ASA and SA were similar in group A and B but
      pregnant subjects had a slower uptake and a lower peak level than controls. The
      late elimination phase for their compound did not differ between the groups. Nine
      pregnant women with normal pregnancies had their bleeding time measured by a
      modified Ivy technique using a Simplate II device before, at the end of, and two
      weeks after daily administration of 75 mg ASA for two weeks. All had a normal
      bleeding time before and two weeks after the end of the medication. Eight of the
      nine subjects had an increased bleeding time by Ivy tests, (p < 0.01) whereas the
      bleeding time assessed by Duke's method was within normal limits. These studies
      suggest that during pregnancy changes of the uptake rate and distribution volume
      modulate the pharmacokinetics of ASA and that this drug given in low dosage to
      gravidae marginally alters their platelet function.

PMID- 7823261
TI  - Partogram of a grand multipara: different descent slope compared with an ordinary
      parturient.
AB  - Partograms of 42 grand multipara women (mean 10 previous deliveries) were
      analyzed and compared with the partograms of nulli- or second-/thirdpara women.
      All these full-term pregnancies were normal and the vaginal deliveries were
      spontaneous and non-instrumental. The grand multiparas had the shortest duration
      of the latent phase and the second stage of the delivery, but the active slope of
      the cervical dilation was in all groups same, on the average 2.8 cm/hour. The
      station of the presenting part of the fetus remained in the grand multipara group
      significantly higher than in the other parturients for the whole first stage of
      labor. During this delayed descent the normal rotation of the fetal head from
      occiput transverse to occiput anterior position was delayed and fetuses were
      often delivered in a low transverse head position. The cephalopelvic
      disproportion need not be the most obvious reason for a slow descent in a grand
      multipara delivery, but slow descent can be caused by the physiological changes
      due to the great number of previous pregnancies.

PMID- 7823262
TI  - CK-BB as indicator of prenatal brain-cell injury in fetuses with absent or
      reverse end-diastolic flow velocities of the umbilical arteries.
AB  - The purpose of this study is to determine the levels of brain type isoenzyme of
      creatine kinase (CK-BB) as a possible indicator of a pre-existing intrauterine
      brain-cell damage in cord blood sera of fetuses with preceding absent or reverse
      end-diastolic flow velocities of the umbilical arteries (AREDFV). CK-BB isoenzyme
      activities were determined in umbilical cord sera of 13 newborn infants with
      preceding AREDFV and in 14 fetuses with low end-diastolic flow velocities (LEDFV)
      of the umbilical arteries. 50 newborn infants with elective cesarean section and
      normal umbilical artery blood flow velocity waveforms were used as controls. Two
      tailed Student's t-test and Fischer's exact test were used for statistical
      evaluation of the results. CK-BB isoenzyme activity did not depend on gestational
      age. Fetuses with AREDFV showed a significant increase in CK-BB values, whereas
      fetuses with LEDFV had CK-BB activities within the normal range of the controls.
      The elevated CK-BB values of the AREDFV group were not correlated with fetal
      acidosis at birth. Brain-cell injury with leakage of CK-BB isoenzyme might be
      present in fetuses with AREDFV even before (preterm) delivery.

PMID- 7823264
TI  - Relevance of the miscarriage-new pregnancy interval.
AB  - There is a wide divergence of opinion concerning the interval a woman should wait
      after a miscarriage before attempting a new pregnancy ("pregnancy interval").
      Many authors recommend waiting 3-4 months in order to reduce the risk of another
      miscarriage [3, 6, 17, 21]. This retrospective study investigated whether a
      longer pregnancy interval lowers the risk of repeat miscarriage (R-risk) and/or
      prematurity. The association between parity and R-risk was also analyzed. Results
      showed that there are no proven reasons to recommend a waiting period between a
      miscarriage and a subsequent pregnancy, because the R-risk was around 20%
      irrespective of interval duration. Prematurity too is not influenced by a waiting
      period after miscarriage. There was, however, an association between parity and R
      risk and risk of prematurity: nulliparae were more likely to have a repeat
      miscarriage (p < 0.05) or a preterm delivery in the next pregnancy (p < 0.05)
      than women who had already given birth to a child.

PMID- 7823263
TI  - Relationship between amniotic fluid and maternal blood nutrient levels.
AB  - To study the relationships between amniotic fluid and maternal blood nutrient
      concentrations, we obtained amniotic fluid and blood samples simultaneously from
      76 pregnant women at around 17 weeks gestation. Folate and vitamin B-12 levels
      were measured by microbiological assay and radioassay, respectively, and zinc,
      copper and iron levels by atomic absorption spectrophotometry. Mean
      concentrations of plasma and red blood cell (RBC) folate and plasma copper of the
      pregnant women were 38 (+/- 1, SD), 1,501 (+/- 374) nmol/L, and 32.7 (+/- 4.8)
      mumol/L, respectively, all of which were higher than those of healthy non
      pregnant controls (p < 0.001). Mean concentrations of plasma vitamin B-12, zinc
      and iron levels and RBC zinc were 320 (+/- 130) pmol/L, 12.2 (+/- 2.3), 21.7 (+/-
      6.1) and 177 (+/- 30) mumol/L and these were similar to those of non-pregnant
      controls. Amniotic fluid folate, zinc, copper and iron concentrations were 21 (+/
      13) nmol/L, 1.4 (+/- 0.6), 1.7 (+/- 0.6) and 6.8 (+/- 2.1) mumol/L,
      respectively, which were significantly lower than plasma levels (p < 0.001).
      However, this relationship was reversed for vitamin B-12 (650 +/- 420 pmol/L).
      Significant correlations were found between amniotic fluid and maternal plasma
      and RBC for folate, and between amniotic fluid and maternal plasma for vitamin B
      12 (p < 0.001). No such correlations were observed for zinc, copper and iron.
      There was no correlation between amniotic fluid and/or blood nutrient
      concentrations and pregnancy outcome including birth weight of infants.

PMID- 7823265
TI  - Clinical application of pulsatility index of flow volume to detect the
      hemodynamic changes in IUGR fetus.
AB  - We attempted to assess feto-placental circulation in fetuses with intrauterine
      growth retardation (IUGR) by calculating the pulsatility index of flow volume
      (PIQ) based on the quantitative measurement of blood flow. Doppler sound was
      processed by an analog to digital converter and a frequency analyzer.
      Multiplication of frequency and signal strength of the Doppler sound at a certain
      time theoretically represents a value proportional to flow volume. Using this
      value, we calculated PIQ of the descending aorta, umbilical artery, and middle
      cerebral artery in normal fetuses, IUGR fetuses, and distressed fetuses during 24
      41 weeks gestation. The PIQ of the fetal descending aorta in the IUGR fetus was
      significantly higher than that of the normal fetus. When cutoff value was set to
      mean +1 SD, abnormal PIQ was observed in 88% of IUGR fetuses. In contrast, the
      abnormal pulsatility index of maximal flow velocity (PIV) of the descending aorta
      was observed in only 62% of IUGR fetuses. In the distressed fetuses, both PIQ and
      PIV of the umbilical artery increased, and these indices of the middle cerebral
      artery markedly decreased. It is suggested that the increased PIQ of the
      descending aorta is an early indicator of changes in the fetal circulation in
      IUGR fetuses.

PMID- 7823266
TI  - Basal ganglia and thalamic calcification following intrauterine intravascular
      transfusion.
AB  - In recent years intrauterine intravascular transfusion has become the method of
      choice for the treatment of severe fetal erythroblastosis. Despite the
      association of the procedure with fetal complications such as bradycardia and
      overtransfusion, later neonatal neurological consequences have been only rarely
      reported. A case is described of a neonate who underwent repeated intrauterine
      intravascular transfusion for treatment of erythroblastosis and who later
      developed calcification in the thalamus and the basal ganglia. The possible
      pathogenetic mechanisms are discussed.

PMID- 7823267
TI  - Fetoneonatal hydrops from human parvovirus B19. Case report.
AB  - Authors report the case of a newborn who died just a few hours after the birth as
      a result of intrauterine Parvovirus B19 infection. Diagnosis of fetal hydrops was
      made by ultrasound examination at the 25th week of pregnancy. Etiology was
      established on the basis of specific antibody findings in the serum of the
      mother, the fetus (by cordocentesis), and the neonate; B19 virus was then
      observed in the fetus and the neonate tissues after death using the dot-blot
      hybridization assay and the polymerase chain reaction technique for viral DNA.
      The severe fetal anemia was treated with intrauterine transfusions, but achieved
      poor results. The pathogenesis of fetal hydrops and advisability of intrauterine
      treatment in such cases are discussed.

PMID- 7823268
TI  - Near infrared spectroscopy used to observe changes in fetal cerebral
      haemodynamics during labour.
AB  - Near Infrared Spectroscopy (NIRS) has been used in the neonate to observe changes
      in the cerebral haemodynamics and concentration of oxygenated haemoglobin.
      Specific changes have been demonstrated in response to spontaneous bradycardias
      and alterations in the inspired oxygen concentration. We report here changes in
      fetal cerebral haemodynamics using NIRS in response to rapid spontaneous delivery
      and the "topping up" of a maternal epidural with bupivacaine. NIRS offers a new
      way of observing changes in cerebral haemodynamics in the fetus during labour.

PMID- 7823269
TI  - Cyclosporine A upregulates interleukin-6 gene expression in human gingiva:
      possible mechanism for gingival overgrowth.
AB  - Cyclosporine A (CsA) is a widely used immunosuppressant for transplant patients
      and is also used for the treatment of a wide variety of systemic diseases with
      immunologic components. A prominent side effect of CsA administration is gingival
      overgrowth. It has been postulated that CsA alters fibroblast activity through
      effects on various cytokines such as the interleukins, however, as yet, data
      concerning the molecular mechanisms involved in connective tissue proliferation
      are still preliminary in nature. The purpose of this study was to evaluate
      interleukin-6 (IL-6) gene expression in gingival tissues of patients receiving
      CsA therapy and exhibiting gingival overgrowth. Radioimmunoassay (RIA)
      demonstrated a significant difference in tissue levels of IL-6 as mean +/- SEM.
      IL-6 content in CsA-stimulated tissue was 184.3 +/- 30.2 ng/mg total protein
      versus 23.3 +/- 6.5 ng/mg total protein in control tissue. In situ hybridization
      indicated that overgrown gingival tissues from patients taking CsA had a
      significantly higher content of IL-6 mRNA when compared to control tissues.
      Expressing IL-6 mRNA levels as silver grains/cell, CsA-stimulated tissue had
      166.9 +/- 12.0 grains of IL-6 mRNA/cell while control tissue had 12.8 +/- 3.0
      grains of IL-6 mRNA/cell. These results demonstrate that CsA therapy results in
      increased levels of IL-6 protein and IL-6 mRNA in overgrown human gingival
      tissues. This is the first report of CsA-upregulated IL-6 gene expression in
      vivo, and may explain in part the molecular mechanisms responsible for CsA
      induced gingival overgrowth.

PMID- 7823270
TI  - Efficacy of mouthrinses in inhibiting the development of supragingival plaque
      over a 4-day period of no oral hygiene.
AB  - This study was a first stage evaluation of the plaque inhibitory properties of an
      experimental cetylpyridinium chloride (CPC)/essential oil mouthrinse. The study
      was a formulation, not ingredient, evaluation and comparisons were made with
      established mouthrinse products. The 5 rinses tested were: the experimental
      formulation; a triclosan/copolymer prebrushing mouthrinse; two negative control
      rinses, which differed only in color; and as a positive control, a 0.2%
      chlorhexidine mouthrinse. The study used a 5 cell, 4-day plaque regrowth, double
      blind crossover design in which 15 subjects participated. Allocation of
      mouthrinse sequences was accomplished using 3 replicates of a 5 x 5 Latin square,
      incorporating balance for carryover. On Day 1, subjects received a scaling and
      polishing to reduce plaque, ceased toothcleaning, and commenced rinsing twice
      daily, under supervision, with the randomly assigned rinse. Rinsing time for the
      experimental and one negative control rinse was 30 seconds and for the other
      rinses was 60 seconds. On Day 5, plaque was scored by both index and area.
      Differences in plaque regrowth between the rinse groups were highly significant.
      The order of efficacy from the most effective was: chlorhexidine rinse (positive
      control); experimental CPC/essential oil rinse; triclosan/copolymer rinse; and
      the negative control rinses. From the calculated confidence intervals each rinse
      differed significantly from each other rinse, except for the two negative control
      rinses which were comparable to each other. Proportionately, the CPC/essential
      oil rinse was positioned 30 to 50% between the triclosan/copolymer rinse and the
      chlorhexidine (positive control). These findings suggest that the CPC/phenolic
      rinse would seem worthy of further evaluation for adjunctive benefits to oral
      hygiene.

PMID- 7823271
TI  - Comparison of a conventional probe with electronic and manual pressure-regulated
      probes.
AB  - We compared the accuracy, consistency, time, comfort, and cost of probing with a
      conventional hand probe (CP) with 3-mm banded markings, a manual pressure
      regulated probe (MP), and two electronic probes (IP and FP). Twenty (20)
      examiners used all four probes on a test block to determine accuracy;
      measurements compared favorably to the reference block. Two calibrated examiners
      probed the Ramfjord teeth of 10 periodontal patients on maintenance regimens, six
      sites per tooth (n = 708), with all four probes; measurements were repeated after
      one week. Wilcoxon signed-rank test showed the CP measured more deeply (P <
      0.0001) than MP, FP, and IP with mean differences of 0.40, 0.67, and 0.58
      respectively. MP measured more deeply (P < 0.001) than FP and IP, with mean
      differences of 0.27 and 0.18 mm. There was no difference between FP and IP. Time
      (min:sec) required by one examiner to perform full mouth probing on six subjects
      (minimum of 26 teeth each) was CP = 3:59; MP = 4:18; FP = 6:16; and IP = 7:23.
      Subjects rated FP and IP as slightly more uncomfortable than CP or MP. Cost per
      1,000 uses was computed based on available data. The IP and FP took longer to
      perform and cost more per procedure than did the CP and MP. Spearman rank-order
      correlation revealed that only probe depths measured by CP and MP were well
      correlated (rs = 0.67). Although some statistically significant differences were
      found between probes, no differences were considered to be of clinical
      significance when probing periodontally healthy or maintenance patients.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7823272
TI  - Effect of local metronidazole application on periodontal healing following guided
      tissue regeneration. Clinical findings.
AB  - The effect of periodontal healing after guided tissue regeneration (GTR) in
      association with local application of metronidazole gel was evaluated in this
      study. Twelve patients with one pair of vertical periodontal bone defects of
      comparable size and configuration participated in the study. In a matched paired
      design, the test defects were treated by GTR using expanded
      polytetrafluoroethylene (ePTFE) membranes in combination with local application
      of metronidazole gel. The controls were treated in the same way except for
      application of metronidazole. During the first month of membrane implantation, no
      statistically significant differences between test and control surfaces were
      noted with respect to inflammation of the marginal gingiva. Six weeks following
      insertion, the membranes were removed. Six months after removal of the membrane,
      the median gain in probing attachment level as a percentage of the initial defect
      depth was 92% for test defects and 50% for control defects (P = .001). No
      statistically significant differences were found between test and control sites
      regarding plaque, bleeding on probing, reduction in pocket depth, gain in bone
      height, or recession of the gingival margin. In conclusion, the results of the
      present study indicate that local application of metronidazole gel has a
      beneficial effect on healing of periodontal vertical defects treated by guided
      tissue regeneration.

PMID- 7823273
TI  - Effect of local metronidazole application on periodontal healing following guided
      tissue regeneration. Microbiological findings.
AB  - The bacteriological colonization of healing periodontal defects was investigated
      after treatment with guided tissue regeneration using expanded
      polytetrafluoroethylene membranes together with local metronidazole gel (25%, 250
      mg/g). Twelve patients, each with one pair of comparable defects, had the test
      defect treated with the membrane plus metronidazole gel and the control defect
      treated with the membrane alone. Thirty weeks after removal of the membrane, the
      median gain in probing attachment level as a percentage of the initial defect
      depth was 92% for the test defects and 50% for the control defects (P = 0.001).
      The median number of cultivable bacteria decreased from 1.2 x 10(6) at the
      presurgical examination to 3.0 x 10(5) at the one week examination in the test
      group (P = 0.02), whereas an increase was observed in the control group.
      Similarly, a lower median proportion of black-pigmented Gram-negative anaerobic
      rods was observed one week postsurgically in the test group (0.004%) compared to
      the control group (3.5%) (P = 0.02). Two weeks after membrane insertion, and at
      all following examinations, no microbiological differences between test and
      control group were observed. Consequently, the influence of the metronidazole gel
      on the treatment result appears to have been confined to the initial regeneration
      phase. Despite the good clinical results in the test group, all membranes from
      both test and control pockets were heavily colonized with bacteria at the time of
      removal. To ensure maximal periodontal regeneration with formation of bone,
      future research in this area should concentrate on reducing the microbial
      colonization of the wound area.

PMID- 7823274
TI  - Subepithelial connective tissue grafts in the treatment of gingival recessions. A
      comparative study of 2 procedures.
AB  - Thirty (30) class I and class II recessions in 30 subjects were treated with a
      subepithelial connective tissue graft procedure. In one group (15 sites), the
      surgery was carried out in a traditional fashion: the epithelial collar of the
      graft was preserved and left exposed (CTG group). In the second group (15 sites),
      the epithelial collar of the graft was removed and the recession areas were
      conditioned with citric acid. The graft was then sutured and completely immersed
      under the facial flap which was coronally repositioned (CR group). Clinical
      assessments included probing depth, probing attachment level, surface area of the
      recession, and gingival width. These measurements were taken at baseline and at 6
      months. In addition, an esthetic evaluation was done. The differences between
      treatments were not statistically significant except for the augmentation of
      gingiva (P < or = 0.05). Based on the midfacial measurements taken in the central
      area of the recession, the mean percentage of root coverage was 69.2%. In the CR
      group, 3 of the 15 recessions exhibited complete root coverage; the gingival
      augmentation was 65.5%. In the CTG group, 5 of the 15 recessions exhibited
      complete root coverage; the gingival augmentation was 94.4%. The mean surface
      area of root exposure was reduced from 13.82 mm2 and 13.67 mm2 to 2.15 mm2 and
      2.34 mm2 for the CR group and the CTG group, respectively. One-hundred percent
      (100%) of good-to-moderate esthetic results were found by a panel of independent
      examiners; there was tendency toward better results in the CR group.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7823275
TI  - Smokeless tobacco effects on monocyte secretion of PGE2 and IL-1 beta.
AB  - The use of smokeless tobacco (ST) products is associated with mucosal lesions,
      gingival recession, and attachment loss at the site of tobacco placement.
      Monocytes/macrophages are primary producers of PGE2 and IL-1 beta, inflammatory
      mediators which are thought to play a role in the destruction of the
      periodontium. The purpose of this study was to determine the effect of ST alone
      and in combination with a major stimulator of inflammation, bacterial
      lipopolysaccharide (LPS), on monocyte secretion of these mediators. Peripheral
      blood monocytes (PBM) were isolated by counterflow centrifugal elutriation from
      15 healthy donors who were non-ST users. PBM were incubated for 24 hours in RPMI
      1640 containing various concentrations of ST (0%, 0.005%, 0.01%, 1%) with or
      without 10 micrograms/ml LPS (Porphyromonas gingivalis LPS or Escherichia coli
      LPS). Of the ST preparations, only 1% ST resulted in PBM mediator secretion (7.7
      +/- 2.0 ng/ml for PGE2 and 1.3 +/- 0.2 ng/ml for IL-1 beta) above that of control
      (unstimulated) cultures. Furthermore, the combination of 1% ST and LPS resulted
      in a potentiation of PGE2 release (5-fold for E. coli LPS + 1% ST and 10-fold for
      P. gingivalis LPS + 1% ST; P < 0.0001, one-way ANOVA) relative to the LPS
      preparations alone. In contrast, PBM IL-1 beta release decreased more than 2-fold
      upon E. coli LPS and 1% ST exposure, relative to treatment with E. coli LPS alone
      (P < 0.0001, one-way ANOVA).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7823276
TI  - Contaminated implant surfaces: an in vitro comparison of implant surface coating
      and treatment modalities for decontamination.
AB  - The relationship between implant surfaces and decontamination treatments was
      studied in vitro to determine which implant surfaces were most effectively
      decontaminated, and which treatment was most effective for treating a particular
      implant surface. The implants used in the study were press fit cylindrical
      titanium units with machined, plasma sprayed, and hydroxyapatite-coated surfaces.
      Radioactive endotoxin (125I-LPS) was prepared from Porphyromonas gingivalis (ATCC
      33277). Implants were coated with 125I-LPS and treated by burnishing with a
      cotton pellet soaked in water, citric acid solution (CA), or 0.12% chlorhexidine
      (CHX); or treated with an air-powder abrasive (AIR). Radioactivity was determined
      after each of two treatment cycles. The results for each implant surface were
      analyzed using ANOVA to determine differences between treatments. The remaining
      125I-LPS after two treatment cycles were: for machined implants AIR < CA, with
      AIR = water = CHX and water = CHX = CA; for plasma sprayed implants AIR < water =
      CHX = CA; for hydroxyapatite implants AIR = CA < water < CHX. In evaluating
      treatment modalities, it was found that machined implants were decontaminated
      more effectively than the other surfaces by all treatments; the exception was
      citric acid treatment which was equally effective on either machined or
      hydroxyapatite surfaces. These results indicate that machined implants (without
      surface coating) are most readily decontaminated by a variety of methods; this
      characteristic should be considered, since long-term success of implants may
      involve treating periimplantitis. Further, the results indicate that air
      abrasives are effective for decontaminating implant surface, with the exception
      that hydroxyapatite coated surfaces can be treated equally with air abrasives or
      citric acid.

PMID- 7823278
TI  - Short-term healing of autogenous and allogeneic bone grafts after sinus
      augmentation: a report of 2 cases.
AB  - Sinus augmentation to facilitate the placement of cylindrical endosseous implants
      in the posterior maxilla has become more commonplace, and many different
      materials have been used for the sinus graft. The results of two sinus
      augmentation procedures, one grafted with demineralized freeze-dried bone (DFDB)
      and the other with autogenous iliac bone, are presented. Bone cores were obtained
      with a trephine drill from the grafted regions at the time of implant placement.
      Eight implants were placed into the grafted areas in each subject. The sample
      from the sinus grafted with autogenous bone was obtained 8 months postoperatively
      and the bone core from the sinus grafted with DFDB was taken 16 months
      postoperatively. The bone specimens were subsequently examined under light
      microscopy. The autogenous specimens demonstrated new bone formation with
      increased quantity and improved quality when compared to the specimens obtained
      from the sites grafted with allogeneic bone. All 8 implants placed into the
      autogenous grafts were clinically osseointegrated at stage 2. At 16-months
      postsurgery, the bone core taken from the site grafted with DFDB demonstrated
      poor bone quality and still contained remnants of the graft material in the
      region approximating the sinus membrane. Two of the 8 implants placed into the
      allogeneic grafts failed at stage 2. These findings suggest that autogenous sinus
      grafts produce bone of adequate quantity and quality for implant placement,
      whereas DFDB sinus grafts are not completely remodeled by the host and may
      produce bone of insufficient quality and quantity for predictable implant
      placement.

PMID- 7823277
TI  - Molecular basis of leukocyte adhesion molecules in early-onset periodontitis
      patients with decreased CD11/CD18 expression on leukocytes.
AB  - We analyzed the cell-cell adherence related to CD11/CD18 and CD18 mRNA in
      individuals with decreased CD11/CD18 expression on their neutrophil surface.
      Epstein Barr virus-transformed B cell lines were developed from one localized
      juvenile periodontitis (LJP) patient with decreased CD11/CD18 in the peripheral
      blood neutrophils and without systemic diseases; two siblings with generalized
      prepubertal periodontitis (GPP) caused by leukocyte adhesion deficiency (LAD);
      another LJP patient; one localized prepubertal periodontitis (LPP) patient; and
      two healthy subjects. Adhesion of leukocytes to each other was measured as
      cluster formation by aggregation assay. The length and the amount of CD18 mRNA
      expressed in the cell lines were analyzed by Northern blotting using the 32P
      labeled CD18 cDNA. The coding region of the mRNA was analyzed by the reverse
      transcription-polymerase chain reaction method. Base-mismatches between CD18 mRNA
      and the 32P-labeled RNA probe synthesized from CD18 cDNA were analyzed by RNase
      protection assay. In the adherence assay, cells from the LJP patients with
      decreased CD11/CD18 formed more clusters of smaller size and fewer cells than
      those of the other subjects. The cells from GPP and LAD patients did not
      aggregate and did not form clusters either in the absence or presence of PMA.
      There were no differences in the length and the amount of mRNA between the LJP
      patients and the other subjects, while GPP-LAD patients expressed a small amount
      of long mRNA. The whole coding region (2,313 base pairs) of all subjects was
      amplified except for the GPP-LAD patients, and the 5'-region (1,119 base pairs)
      was amplified from all subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7823279
TI  - Clinical use of a bioresorbable matrix barrier in guided tissue regeneration
      therapy. Case series.
AB  - In this case series study 19 Class II furcations and 47 intrabony defects in 59
      patients were treated according to the principles of guided tissue regeneration
      using a bioresorbable matrix barrier. Gingival condition and device exposure were
      assessed at 2 weeks, and 1, 3, 6, and 12 months after surgery. The effect of
      therapy was evaluated by assessing probing depths (PD), probing attachment level
      (PAL), and the position of the gingival margin prior to surgery and 12 months
      after surgery. Mild clinical signs of inflammation in the soft tissue covering
      the device was found adjacent to 3 defects only and limited to the first month of
      healing. Device exposure occurred at 10 out of the 66 defects. At the furcation
      defects, the mean PD reduction amounted to 3.7 mm (P < or = 0.001). Mean gain PAL
      vertical was 3.4 mm and PAL horizontal 3.3 mm (P < or = 0.001), resulting in
      complete closure of 9 out of the 19 defects. Mean gingival recession was 0.2 mm.
      At the intrabony defects mean PD reduction was 5.4 mm and mean gain of PAL 4.9 mm
      (P < or = 0.001). Gingival recession averaged 0.5 mm (P < or = 0.05). It was
      concluded that the use of the matrix barrier in GTR therapy resulted in 1)
      reduced probing depths; 2) pronounced gain of clinical attachment; and 3) a very
      low incidence of gingival pathology, gingival recession, and device exposure.

PMID- 7823280
TI  - [Intravascular ultrasound assessment at the site of balloon angioplasty:
      comparison with quantitative coronary angiography].
AB  - The effect of coronary angioplasty is usually evaluated on the basis of coronary
      angiography. However, angiographic images taken after angioplasty vary and the
      angiographic assessment of the therapeutic success of angioplasty is limited by
      local disruptions and dissections at the site of the dilatation, which are often
      difficult to detect by angiography. Intravascular ultrasound imaging is a new
      method for evaluation of coronary dimensions and wall morphology. Quantitative
      coronary angiographic analysis was compared with intravascular ultrasound
      assessment after balloon angioplasty in 42 patients. A diagnostic ultrasound
      imaging catheter was used during percutaneous transluminal coronary angioplasty
      (PTCA) to image both the lesion and the vessel segment just proximal (reference
      segment). Correlation between angiographic and ultrasound findings of vessel
      diameters and areas at reference segments was closer (r = 0.78, 0.66) than at the
      sites of PTCA (r = 0.54, 0.36). Dilated sites were analyzed in two subgroups
      segregated by degree of lumen eccentricity. An eccentric vessel lumen, defined as
      a circular shape factor of less than 0.92, was present at 25 of 42 sites. The
      correlation between angiographic and ultrasonic cross sectional area was not as
      close for these eccentric segments (r = 0.37). The difference in luminal areas
      between eccentric lumens estimated by edge detection and densitometry methods was
      0.93 +/- 0.3 mm2, significantly greater than 0.54 +/- 0.31 mm2 in the circular
      group (p < 0.01). Luminal area after balloon angioplasty is clinically important
      to confirm by intravascular ultrasound especially in patients with large
      differences in measured values by quantitative coronary angiography.

PMID- 7823281
TI  - [Clinical features and long-term outcome of non-Q wave myocardial infarction in
      the elderly: comparison with Q wave myocardial infarction].
AB  - The clinical features and long-term outcome of non-Q wave myocardial infarction
      (NQMI) in the elderly were assessed in 24 patients with NQMI and compared with
      those in 48 patients with Q wave myocardial infarction (QMI). NQMI patients had a
      significantly lower maximal peak of serum creatine phosphokinase activity and
      lower incidence of pump failure during the acute phase. In-hospital mortality did
      not differ significantly between the NQMI and QMI patients. Evaluation of acute
      phase coronary angiographic features within 6 hours of onset found a
      significantly higher incidence of infarct-related vessels in the NQMI patients,
      but the frequency of multivessel disease and the level of collateral flow did not
      differ between the two groups. Fifteen of the 24 NQMI patients and 34 of the 48
      QMI patients underwent emergency coronary revascularization procedures of
      percutaneous transluminal coronary angioplasty (PTCA) or intracoronary
      thrombolysis. Successful recanalization was more frequent and the time to
      recanalization was shorter in the NQMI patients. The requirement for coronary
      revascularization (PTCA or coronary artery bypass graft) in the chronic phase for
      residual stenosis did not differ significantly between the two groups. Left
      ventricular ejection fractions were significantly better in the NQMI patients.
      The short- and long-term outcomes in elderly patients with NQMI and QMI were good
      and did not differ between the two groups, probably reflecting the active
      performance of revascularization in the acute and chronic phases.

PMID- 7823282
TI  - [Alteration in ventricular gradient at rest in patients with ischemic heart
      disease].
AB  - The possibility of using alteration in the ventricular gradient (VG) to discern
      the presence of ischemic heart disease was studied in 30 patients with effort
      angina pectoris(AP), 21 with vasospastic angina (VSA), 21 with chest pain
      syndrome (CPS), and 20 healthy volunteers (control). The VG of each consecutive
      heart beat over a 22-sec interval was calculated by microcomputer from resting
      Frank-lead X, Y, Z scalar electrocardiograms. The mean values and standard
      deviations (SD) for the azimuth, elevation, and magnitude of the VG in each group
      were calculated. The SD and SD/mean ratios for each parameter were used as
      indices of VG alteration in the groups, and the indices were compared. The SD and
      SD/mean for the magnitude and elevation of VG were significantly greater in the
      AP group than in the CPS and control groups. The SD for the azimuth of VG was
      significantly greater in the AP group than in the CPS and control groups (p <
      0.01). The SD and SD/mean for the magnitude of VG were greater in the AP group
      than in the VSA group (p < 0.01). The SD/mean for the elevation and magnitude of
      the VG were greater in the VSA group than in the control group (p < 0.01). The
      SD/mean of the magnitude of the VG was found to be the best index, as it was
      higher than the upper limit of the control group. The sensitivity and specificity
      were 80 and 91% (AP vs CPS, p < 0.001), and 43 and 91% (VSA vs CPS, not
      significant), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7823283
TI  - [Comparison of initial and delayed myocardial imaging with beta-methyl-p-[123I]
      iodophenylpentadecanoic acid in acute myocardial infarction].
AB  - Myocardial imaging using beta-methyl-p-[123I]-iodophenylpentadecanoic acid
      (BMIPP) of 15 patients with acute myocardial infarction was performed to assess
      "fill-in" and "washout" defects in the delayed myocardial image. The initial and
      delayed images were evaluated by a visual and quantitative washout rate method.
      Visual judgement found 8/180 (4%) segments showed "fill-in" defects, and 24/180
      segments (13%) showed "washout" defects. There was no relationship between days
      from onset to the study and the frequency of fill-in and washout defects. The
      mean washout rate in the segments with "fill-in" defects was 9.0 +/- 16.6%, and
      that of "washout" defects was 24.9 +/- 18.1% which was significantly higher than
      in controls (8.7 +/- 15.4%, p < 0.05). There was no correlation between mean
      washout rate and total blood lipids, total cholesterol, triglyceride and HDL
      cholesterol. Therefore, neither time from onset nor blood lipids level was
      related to changes from the initial image to the delayed image. These changes may
      be due to relative (false) findings due to changes in circumference, and may be
      based on myocardial characteristics after myocardial infarction and/or
      reperfusion.

PMID- 7823284
TI  - [Change in cross-bridge activation rate constant (Kac) after six-minute walk in
      patients with heart failure].
AB  - Cardiac adrenergic activity is increased in patients with congestive heart
      failure (CHF) and is excessively increased during mild exercise. Changes in
      cardiac adrenergic activity were examined in normal individuals and patients with
      CHF before and after mild exercise using the cross-bridge activation rate
      constant (Ka), which may represent the adrenergic activity related to the working
      left ventricular myocardium. Ten normal volunteers and 31 patients with stable
      CHF underwent echocardiography. The left ventricular ejection fraction (LVEF) was
      measured in all the CHF patients using left ventriculography or radionuclide
      cineangiography. The patients were classified into two groups: group 1 with an
      LVEF > or = 50% (n = 16) and group 2 with an LVEF < 50% (n = 15). The cause of
      CHF was old myocardial infarction in 25 patients and dilated cardiomyopathy in 6.
      All subjects exercised by walking for 6 min after resting in the supine position
      for 30 min. The blood pressure, electrocardiogram, phonocardiogram, and M-mode
      echocardiogram were recorded simultaneously before and after exercise. The values
      of Ka and Kac (Ka corrected for the individual heart rate) were calculated from
      the QS2 interval and the heart rate (HR) as follows: Ka = 3/QS2 interval, and Kac
      = Ka +0.0249 (66-HR). Before exercise, the HR was significantly higher in group
      2, but the Kac value showed no significant difference between all three groups.
      The increase of HR with exercise (delta HR) and the Kac value after exercise were
      not significantly different between all three groups.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7823285
TI  - Cost effectiveness of radiofrequency catheter ablation versus medical treatment
      for paroxysmal supraventricular tachycardia in Japan.
AB  - This study evaluated the cost of performing radiofrequency catheter ablation in
      Japanese patients with paroxysmal supraventricular tachycardia refractory to
      antiarrhythmic drug therapy in comparison with the cost of continuing
      pharmacologic treatment. Twenty patients (mean age 44 +/- 14 years) underwent
      successful ablation: 15 patients with Wolff-Parkinson-White syndrome and five
      with atrioventricular nodal reentrant tachycardia. The mean duration of symptoms
      was 77 +/- 60 months. The patients had been treated with 2.6 +/- 1.7
      antiarrhythmic drugs before undergoing ablation. Charges derived from hospital
      bills were compared with the outpatient charges for the year before ablation. The
      mean hospital stay for the ablation procedure was 4.3 +/- 0.5 days. The mean
      total charge for ablation was 982,806 yen +/- 103,195, and 5.7 +/- 0.7 times the
      outpatient charges in the previous year. The majority of radical cure charges
      were the costs of the electrode catheters used in the ablation procedure. All
      patients had a successful outcome and required no additional antiarrhythmic drug
      therapy. If medical treatment were continued without ablation, the mean total
      life-expectancy charges were estimated at 7,064,726 yen +/- 3,116,621, 41.0 +/-
      19.2 times the outpatient charges. The total life charges of medical treatment
      were significantly more than the total ablation charges (p < 0.001). This study
      suggests that radiofrequency catheter ablation is of clinical benefit in treating
      paroxysmal supraventricular tachycardia, and markedly reduces the cost of
      definitive therapy. This strategy appears to be more economical than
      pharmacologic treatment.

PMID- 7823286
TI  - [Chaotic attractor of the left ventricular wall motion in normal heart healthy
      subject].
AB  - To analyze the entire left ventricular wall motion, not the decomposed motion,
      nonlinear mathematical techniques were used to describe graphically time series
      data for the left ventricular contraction. Time series data of the left
      ventricular wall motion were recorded by M-mode echocardiography, and embedded
      into three-dimensional phase space. The largest Lyapunov exponents, a measure of
      the rate of divergence in phase space, were calculated to detect the sensitive
      dependence on initial conditions. The reconstructed attractor of the left
      ventricular contraction showed a lower dimensional strange attractor, and
      calculation of the Lyapunov exponents indicated sensitivity to initial
      conditions. These results suggest that time series data of the left ventricular
      contraction show the characteristics of deterministic chaos. The chaotic system
      can provide an intelligent and flexible control system. Our results suggest that
      the circulatory control system, which mediates the cardiac contractility, may be
      a flexible dynamic compatible with deterministic chaos.

PMID- 7823287
TI  - [Diagnosis of coronary artery dehiscence and pseudoaneurysm after modified
      Bentall operation by Doppler color flow imaging: a case report].
AB  - This 48-year-old man presented with anterior chest and back pain in 1981. He was
      treated with replacement of the ascending aorta and aortic valve under a
      diagnosis of dissection of the ascending aorta with severe aortic regurgitation.
      He underwent modified Bentall reoperation for the dilation of the aortic root in
      1991. Postoperative two-dimensional echocardiography was performed because of
      sustained atrial flutter. An echo-free space was detected between the aorta graft
      and aorta wrapping on the short-axis view. Doppler color flow imaging revealed
      blood flow from the left coronary artery graft into the echo-free space. This
      leakage was suspected to be the cause of the echo-free space. Transesophageal
      echocardiography was performed to conform this hypothesis, which revealed blood
      flow from the left coronary artery graft into the echo-free space in systole and
      flow into the left coronary artery graft from the echo-free space in diastole.

PMID- 7823288
TI  - Influence of the herbicide Linuron on growth rate and gap-junctional
      intercellular communication of cultured endothelial cells.
AB  - On the basis of in vivo toxicological long-term tests performed on rodents, the
      herbicide Linuron [3-(3,4-dichlorophenyl)-1-methoxy-1-methylurea] has been
      classified by the U.S. Environmental Protection Agency (EPA) (1988) as a class C
      carcinogen (possibly carcinogenic to humans). However, when Linuron was analyzed
      for genotoxicity, negative results were obtained. An epigenetic, tumor-promoting
      potential was hence suspected to be responsible for the oncogenic activity of the
      molecule. In the absence of in vivo data concerning the tumor-promoting activity
      of the herbicide and being well established that tumor promoters interfere with
      the cell growth rate and gap-junctional permeability, the effects of technical
      grade Linuron and of its trade formulation (Linuron 50) on these parameters were
      investigated. This is especially important in the case of the formulated
      preparation for a correct estimate of the health hazard to humans. Cytotoxicity
      and gap-junctional intercellular communication (GJIC) assays were performed on
      the endothelial cell line F-BAE GM 7373, an in vitro cell system known to be
      responsive to the biological effects of tumor promoters. A time- and dose-related
      cytotoxic effect was found for both Linuron and Linuron 50, the latter being the
      far more cytotoxic of the two. However, when tested at noncytotoxic
      concentrations over a period of 48 h, neither Linuron nor Linuron 50 altered the
      capacity of F-BAE GM 7373 cells to intercommunicate. On the basis of the results
      obtained, the possibility that Linuron and Linuron 50 are endowed with tumor
      promoting activity is discussed. In vivo studies on tumor-promoting and genotoxic
      activity are in progress to complement the information available on the
      toxicological properties of Linuron and its trade preparation.

PMID- 7823289
TI  - In vivo studies on enzymatic induction activity of Linuron.
AB  - The effect of the ureic herbicide Linuron [3-(3,4-dichlorophenyl)-1-methoxy-1
      methylurea] on the levels of some hepatic xenobiotic metabolizing enzymes was
      studied in rats. The cytochrome P450-dependent monooxigenase activities of aryl
      hydrocarbon hydroxylase (AHH) and of aminopyrine N-demethylase (APD) were
      measured in rat livers after a 14-d treatment by gavage with Linuron. AHH was
      employed as a marker of the catalytic activity of P450IA1 and APD as a marker of
      the catalytic activity of P450IIB1/2. Furthermore, the enzymatic activities of
      the cytosolic via glutathione detoxifying enzymes glutathione peroxidase and
      glutathione S-transferase were assessed. Three doses of Linuron (both as pure
      compound and as commercial preparation) were tested. The doses tested were 150,
      300, and 450 mg/kg body weight for the pure compound and 315.8, 631.6, and 947.4
      mg/kg for the commercial preparation. Differences were found in the relative
      liver weight only in rats treated with the commercial formulation. The aryl
      hydrocarbon hydroxylase activity was increased with all the tested doses of pure
      and commercial Linuron. A reduction in the aminopyrine N-demethylase activity was
      noted for the highest dose of pure Linuron, whereas an increment in this activity
      was observed for all the doses of the commercial preparation tested. The activity
      of glutathione peroxidase was not affected by treatment with the pure product;
      however, an increment in activity was observed at all the tested doses of the
      commercial preparation. The glutathione S-transferase activity was reduced in
      both cases.

PMID- 7823291
TI  - Investigation of increased incidence in childhood leukemia near radio towers in
      Hawaii: preliminary observations.
AB  - Twelve children from the Waianae Coast, Hawaii, were diagnosed with acute
      leukemia from 1979 to 1990. The standardized incidence ratio (SIR) of 2.09 (95%
      confidence interval (CI) 1.08 to 3.65) indicates a significant increase. Seven
      cases occurred between 1982 and 1984 and were unusual in terms of sex, age, and
      type of leukemia. A case-control study (12 cases, 48 matched controls) explored
      risk factors, including parents' occupation, X-ray exposure, domestic smoking,
      family and medical histories, and distance of children's residence locations to
      low frequency radio towers. The odds ratio (OR) for having lived within 2.6 miles
      of the radio towers before diagnosis was 2.0 (95% CI 0.06 to 8.3). The clustering
      may have been a chance event, but because of its peculiar characteristics, we
      feel it should be noted.

PMID- 7823290
TI  - Dissociation between in vitro cytotoxicity and in vivo cardiotoxicity of two new
      anthracyclines: 3'-deamino-3'-(2-methoxy-4-morpholinyl)doxorubicin and 4'-deoxy
      4'-iodo-doxorubicin.
AB  - The purpose of this study was to examine the cytotoxicity and cardiotoxicity of
      new doxorubicin (DXR) derivatives, 3'-deamino-3'-(2-methoxy-4- morpholinyl)DXR
      (MRA-MT), and 4'-deoxy-4'-iodo-doxorubicin (IDXR), comparing them to doxorubicin
      (DXR). Both anthracycline derivatives were approximately 1.5- to 9-fold more
      active than DXR in inhibiting the colony-formation ability of DU145, HOS, and
      A2780 human cancer cell lines. Anesthetized rats given a single intravenous
      (i.v.) dose of DXR 10 mg/kg showed significant changes in both ECG (S alpha T
      segment and QRS complex widening) and hemodynamic parameters (impairment in
      systemic arterial dP/dtmax systolic and diastolic blood pressure), whereas
      animals that received MRA-MT (0.1 and 0.3 mg/kg) had no significant signs of
      acute cardiotoxicity. In this case the animals treated with IDXR 1.2 mg/kg showed
      alterations in the ECG as the animals treated with DXR. In the chronic
      cardiotoxicity study, some animals received MRA-MT (0.03 mg/kg i.v. once a week
      for 3 weeks) and others IDXR (4 mg/kg once a week for 3 weeks). They did not show
      any alteration in ECG and cardiac histological picture. By contrast, DXR (3 mg/kg
      i.v. once a week for 3 weeks) induced a severe cardiomyopathy, characterized by
      progressive widening of S alpha T segment, increase in T wave, and histological
      damage consisting of vacuolations and loss of myofibrils. These results suggest
      that MRA-MT and IDXR are more active in vitro and markedly less cardiotoxic in
      vivo than DXR.

PMID- 7823293
TI  - Mortality rates of liver cancer in Spain: effect of age, birth cohort, and period
      of death.
AB  - Liver cancer is one of the main causes of death in Mediterranean countries. The
      pattern of mortality from liver cancer has been characterized by both
      geographical and temporal variations. In order to clarify its trend and in an
      attempt to hypothesize the future pattern of mortality, we analyzed data from the
      Spanish population, aged more than 35 yr, who died of liver cancer during the
      period of 1975 to 1989. The mortality data were obtained from the National
      Statistical Institute of Spain. We used a log-linear Poisson model to examine the
      effects of age, birth cohort, and calendar period of death. Age is the strongest
      factor in predicting liver cancer mortality according to the models. The sharp
      decrease in liver cancer mortality rates that had occurred in both sexes can be
      attributed to the joint effect of better diagnosis and assignment of metastatic
      tumors to the site of their primary origin, as well as to the modification of the
      International Classification of Diseases (ICD) code.

PMID- 7823292
TI  - Chlorination of drinking water and cancer incidence.
AB  - Epidemiological studies report associations between cancer mortality and type of
      drinking water source. Different studies appeared to lend some support to the
      hypothesis that surface waters contain higher levels of human carcinogens than
      groundwater sources. The possible contaminants that might play such a role are
      the halogenated organic compounds produced by the chemical reaction between
      organic materials in water and chlorine used for disinfection. Chlorine reacts
      with naturally occurring organic compounds in the water to form haloforms.
      Valencia Province of Spain relies almost exclusively on groundwater for its
      public drinking water, but the city and surrounding urban areas rely on
      superficial water. The chlorination used in the superficial water includes
      several phases: prechlorination, coagulation, filtration, and, finally,
      postchlorination, which shows the possible formation of organohalogenated
      compounds. To find an association between stomach and bladder cancer mortality
      with the type of water source, we studied 261 municipalities of Valencia
      Province. We calculated sex-specific standardized mortality ratios for deaths
      occurring between the 1985 to 1989 (census statistics), and we carried out a
      relative-risk calculation associated with the differences between superficial and
      groundwater supplies.

PMID- 7823294
TI  - Spontaneous squamous cell carcinoma of nasal and paranasal structures in the
      Cpb:WU (Wistar random) rat: nasolachrymal duct as major site of origin.
AB  - Spontaneous nasal tumors in ageing rats are very rare. Chronic irritation and
      disruption of nasal, paranasal, buccal, and dental tissues have been associated
      with the occurrence of tumors of the nasal and paranasal structures in rats. To
      find out whether there is a relationship between malocclusion (MO) and nasal
      squamous cell carcinoma (SCC) in Cpb:WU (Wistar random) rats, a total of 899
      untreated control rats (548 males and 351 females) from eight long-term
      toxicity/carcinogenicity studies was screened for nasal tumors and MO. All
      relevant data and the histopathology of the nasal and paranasal structures of a
      sample of these rats (189 males and 197 females from three of the studies) and
      all rats bearing a nasal tumor were subjected to a detailed analysis. Of the 899
      rats, 84 males (15%) and 78 females (22%) suffered from MO. Microscopic
      examination revealed an unexpectedly high incidence of lesions in the
      nasolachrymal duct (NLD): 64 out of 189 males (34%) and 68 out of 197 females
      (34.5%) showed inflammatory changes, with or without squamous metaplasia and/or
      hyperplasia of the lining epithelium of the NLD. The incidence of NLD lesions was
      much higher in the animals with than without MO, suggesting an interaction of
      both phenomena. Eight of the 899 untreated control rats had a nasal tumor; all
      were SCCs and all occurred in males. The origin of the tumors was as follows: 2
      NLD, 2 most probably NLD, 2 presumably NLD, 1 of unknown origin but possibly NLD,
      and 1 probably a cutaneous epidermoid cyst. On the basis of these findings, it
      was concluded that nasal SCC in Cpb:WU (Wistar random) rats prevails in males and
      is primarily associated with chronic inflammation of the NLD rather than with MO,
      although MO probably is an (indirectly) contributing factor.

PMID- 7823295
TI  - A new experimental model for colorectal carcinogenesis in the rat.
AB  - A total of 130 rats were used in various experiments to prepare a new model for
      colorectal carcinogenesis. The experiments resulted in the development of a
      surgical technique that creates a subcutaneous cecal hernia, which allows the
      direct injection of the promoting substance, human bile from percutaneous biliary
      drainage, into the bowel of the rat. The method permits a direct, complete, and
      very easy access of a specific amount of the substance to be tested onto the
      colonic mucosa. The results have proven to be uniformly effective and easily
      reproducible and to ensure safe management of the animal.

PMID- 7823296
TI  - Porcine pulmonary edema with hydrothorax: a review.

PMID- 7823297
TI  - Inhibition of growth and aflatoxin production in Aspergillus parasiticus by
      essential oils of selected plant materials.
AB  - We studied the effect of 13 chemically different essential oils (EO) on the
      mycelial growth of and aflatoxin synthesis by Aspergillus parasiticus. Cinnamon,
      thyme, oregano, and cumin EO were able to stop mycelial growth at only 0.1% in
      the medium, while curcumin, ginger, lemon, and orange EO were unable to inhibit
      totally the growth even at 1% concentration. Coriander, black pepper, mugwort,
      bay, and rosemary EO caused the growth to stop at concentrations between 0.2 and
      1%. The EO most active upon mycelial growth were also the most active against
      aflatoxinogenesis. However, aflatoxin synthesis was inhibited by all the EO at
      higher extent than the mycelial growth.

PMID- 7823298
TI  - Juvenile ossifying fibroma. An analysis of 33 cases with emphasis on
      histopathological aspects.
AB  - Juvenile ossifying fibroma (JOF) is a maxillofacial fibro-osseous lesion that may
      show cell-rich osteoid strands or psammoma-like ossicles. Whether both types are
      variants of a single entity or different lesions under the same diagnostic label
      is a subject of debate. This problem was investigated by analyzing a series of 33
      patients with lesions having one or both of the above histological appearances.
      It was concluded that osteoid strands define a unique fibro-osseous lesion but
      that lesions with psammoma-like ossicles fall within the morphological spectrum
      of cemento-ossifying fibroma. Therefore the term juvenile ossifying fibroma
      should be reserved for the lesion with the osteoid strands.

PMID- 7823299
TI  - Hyperfibers and vesicles in dentin matrix in dentinogenesis imperfecta (DI)
      associated with osteogenesis imperfecta (OI).
AB  - Dentin matrix of deciduous teeth from two patients affected by dentinogenesis
      imperfecta (DI) associated with types IB and IVB osteogenesis imperfecta (OI)
      displayed previously undescribed structures in transmission electron microscopic
      examination. Vesicles were seen in dentin of both patients, and abnormally thick
      collagen fibers (hyperfibers) were found in dentin of the patient with the rare
      type IB OI. Both vesicles and hyperfibers were situated in abnormal, atubular
      areas of dentin. Matrix vesicles, which have normally been identified in mantle
      dentin only, were abundant in selected areas of the affected dentin, thereby
      supporting the concept that dentin matrix in OI is elaborated by successive cell
      generations. The hyperfibers, not previously described in either normal or
      abnormal human dentin, have possibly been formed by fusion of several collagen
      fibers. Further ultrastructural studies of dentin in DI with OI may help to
      clarify the marked clinical variation in teeth of patients affected by OI.

PMID- 7823300
TI  - Candida-associated palatal papillary hyperplasia in HIV infection.
AB  - Oral Candida infections may appear in many guises, especially in HIV-infected
      individuals. Whereas the pseudomembranous and the erythematous forms of oral
      candidiasis are the most frequently encountered in such patients, there appear to
      be further clinical variants of this disease. This paper describes seven dentate
      homosexual AIDS patients who developed papillary hyperplasia of the palate which
      was associated with Candida infection. Such lesions, classically related to
      denture stomatitis, have rarely been described in dentate patients, and this
      report further expands the spectrum of candidal infections seen in HIV disease.

PMID- 7823302
TI  - Human papillomavirus (HPV) types 2 and 57 in oral verrucae demonstrated by in
      situ hybridization.
AB  - Twenty-one cases of verrucae vulgaris (oral warts) were investigated for human
      papillomavirus (HPV)-group specific antigen by immunocytochemistry and for HPV
      types 1, 2, 4, 6, 11, 16, 18 and 57 by DNA in situ hybridization with
      biotinylated probes. Twelve (57%) cases demonstrated the presence of HPV-group
      specific antigen. Fifteen (71%) cases showed the presence of HPV DNA, 13 of which
      (87%) demonstrated both HPV types 2 and 57 in the same cells and 2 of which (13%)
      demonstrated only HPV 2. Six cases were negative for HPV 2 and 57 and all 21
      cases (100%) were negative for HPV types 1, 4, 6, 11, 16 and 18. Results indicate
      the association of a new and as yet unidentified HPV type, closely related to HPV
      2 and 57, with oral warts. The identification of both cutaneous type HPV 2 and
      another type closely related to HPV 2 and 57 in oral verrucae on keratinized and
      non-keratinized mucosal surfaces indicates the possibility of a latent infection;
      three patients had a history of warts on their hands, suggesting autoinoculation.
      This study indicated that future investigations of oral warts, based on a
      correlation of clinical and histological features with HPV types by DNA in situ
      hybridization, are called for.

PMID- 7823301
TI  - Identification of Candida albicans types related to healthy and pathological oral
      mucosa.
AB  - This study comprised 100 healthy dentate adults and 53 patients with either
      chronic erythematous oral candidosis or oral leukoplakic lesions. The presence of
      yeasts was determined by microscopical examination of PAS-stained smears and by
      culture. Biopsy material was obtained from all lesions. The isolated yeasts were
      identified to species level. Strain phenotypes of 147 Candida albicans isolates
      were determined on the basis of the ODDS & ABBOTT procedure (25, 26). Yeasts were
      found in the mouth of healthy dentate individuals both by culture and by smears.
      The identification of hyphae in healthy mucosa indicates that the presence of
      these structures is not an unequivocal sign of candidal infection. The results
      support the view that tobacco smoking may be a predisposing factor for candidal
      infection. Also, the results have shown an association between the occurrence of
      yeasts and the type of leukoplakic lesions. Finally, the strain differentiation
      has indicated an oral mycoflora in patients with candidal lesions disappearing
      after antimycotic treatment which was more homogeneous in composition than in
      patients with irreversible lesions; furthermore, certain strains may possess
      properties which may be important in the development of pathological conditions
      and premalignant changes.

PMID- 7823303
TI  - Influence of inductive chemoradiotherapy on salivary polymorphonuclear leukocyte
      (SPMN) functions in oral cancer.
AB  - Salivary polymorphonuclear leukocyte (SPMN) functions were examined in 18
      patients with oral squamous cell carcinoma and in 20 healthy individuals. SPMN
      obtained from patients before therapy exhibited significantly less FMLP
      stimulated chemotactic activity (132.4 +/- 17.5 cells/0.26 mm2) than that in SPMN
      from controls (177.1 +/- 11.6 cells/0.26 mm2), although no difference in
      phagocytosis was observed. When stimulated with PMA or FMLP, control SPMN
      generated superoxide (O2-) at levels of 50.3 +/- 10.5 pmol/min/10(4) cells and
      88.4 +/- 15.4 pmol, respectively, while SPMN from untreated patients generated
      significantly reduced O2- in the presence of PMA or FMLP (24.3 +/- 3.5 pmol and
      59.5 +/- 9.8 pmol, respectively). Only slightly lower chemiluminescence was
      observed in SPMN from untreated patients however, compared to controls, values
      being 68.0 +/- 18.9 vs 81.3 +/- 14.9 peak mV by PMA and 62.4 +/- 13.7 vs 64.4 +/-
      12.9 peak mV by FMLP. Compared to Candida killing in control subjects (24.9 +/-
      3.1%). SPMN from patients before treatment exhibited significantly reduced
      activity (18.7 +/- 4.9%). Further suppression of the SPMN functions examined was
      observed after chemoradio-therapy. Suppressed SPMN function in cancer patients,
      especially that associated with chemoradiotherapy, may therefore play a part in
      oral candidiasis.

PMID- 7823304
TI  - Generalized gingival enlargement due to accumulation of amyloid-like material.
AB  - Hyaline or amyloid-like substances may be seen in several oral lesions. Some of
      these originate from epithelial cells and some from connective tissue components.
      In this study, amyloid-like material causing gingival enlargement in three
      patients, with eyelid involvement in two, was examined using histochemistry,
      immunohistochemistry and electron microscopy. These accumulations did not share
      the classical features of amyloid such as green birefringence under polarized
      light after Congo red staining. Our findings suggest that epithelial degeneration
      plays an important role in the pathogenesis of these amyloid-like accumulations.
      These substances may be the result of defective amyloidogenesis and our cases may
      represent an oral counterpart of ligneous conjunctivitis or colloid milium of the
      skin.

PMID- 7823305
TI  - Primary angiosarcoma of the alveolar mucosa in a haemodialysis patient: case
      report and discussion.
AB  - A case of a haemodialysis patient with a primitive angiosarcoma of the alveolar
      mucosa is reported. The vascular origin of the tumor was confirmed by the
      immunohistochemical data which showed strong positivity for Factor VIII-related
      antigen and for vimentin, whereas stains for desmin and cytokeratins were
      negative.

PMID- 7823306
TI  - Frequency modulated sound pattern analysis in the lesser bulldog bat: the role of
      interactions between adjacent frequency elements of complex sounds.
AB  - A stereotyped approach phase vocalization response of Noctilio albiventris to
      artificial echoes simulating a virtual approaching object was used to assess the
      ability of the bat to analyze and extract distance information from the
      artificial echoes. The performance of the bats depended on the temporal pattern
      of frequency change of the continuously sweeping frequency modulated (FM)
      component of the signals. When the bats were presented with a CF/FM signal
      containing a time-reversed upward FM sweep, they responded with approach phase
      behavior at a performance level that was significantly below that seen with a
      CF/FM signal containing a naturally structured downward FM sweep. When the FM
      sweep was divided into a series of brief pure tone steps, the extent to which the
      bats showed a difference in their capability to process upward versus downward FM
      sweeps depended on the difference in frequency between the pure tone steps. The
      bats effectively processed downward but not upward FM sweeps when the difference
      in frequency between pure tone frequency elements of the FM sweeps was from about
      100-200 Hz, but they effectually processed both downward and upward FM sweeps
      when the tonal elements composing the FM sweeps were separated by more than about
      200 Hz. This suggests that the ability of the bats to effectively process
      downward but not upward FM sweeps is based on local interactions between adjacent
      frequency elements of the complex sounds.

PMID- 7823307
TI  - Complex behavior induced by egg-laying hormone in Aplysia.
AB  - Previous studies have described a pattern of complex behavior that occurs in the
      marine mollusc Aplysia during egg laying. Egg laying and the behavior are
      initiated by a burst of impulse activity in the neuroendocrine bag cells of the
      abdominal ganglion or by injection of bag cell extract. To more precisely
      identify the factors responsible for inducing the behavior we injected animals
      with egg laying hormone (ELH), one of the neuropeptides secreted by the bag
      cells. We found that ELH causes a behavior pattern similar to what occurs during
      spontaneous egg laying. This includes a temporal pattern of head movements
      consisting of waves and undulations, followed near the beginning of egg
      deposition by a transition to head weaves and tamps and inhibition of locomotion.
      There was also a small decrease in respiratory pumping. Except for respiratory
      pumping, a similar pattern occurred in a second group of animals injected with
      atrial gland homogenate, which is presumed to induce bag cell activity, but not
      in controls. These results further implicate ELH in regulation of the behavior.
      We discuss possible sites of action of ELH and the neural mechanisms by which the
      behavior is controlled.

PMID- 7823308
TI  - A single pair of interneurons controls motor neuron activity during pre-ecdysis
      compression behavior in larval Manduca sexta.
AB  - Manduca sexta molts several times as a larva (caterpillar) before becoming a pupa
      and then an adult moth. Each molt culminates in ecdysis behavior, during which
      the old cuticle is shed. Prior to each larval ecdysis, the old cuticle is
      loosened by pre-ecdysis behavior, which includes rhythmic, synchronous
      compressions of the abdomen. A previous study indicated that motor neuron
      activity during pre-ecdysis compression behavior is driven by an ascending neural
      pathway from the terminal abdominal ganglion. The present study describes a pair
      of interneurons, designated IN-402, that are located in the terminal ganglion and
      belong to the ascending pathway. Each IN-402 is synchronously active with pre
      ecdysis compression motor bursts, and bilaterally excites compression motor
      neurons throughout the abdominal nerve cord via apparently monosynaptic
      connections. The pair of IN-402s appears to be the sole source of rhythmic
      synaptic drive to the motor neurons during the pre-ecdysis compression motor
      pattern. These interneurons play a key role in the production of larval pre
      ecdysis behavior, and are candidates for contributing to the developmental
      weakening of pre-ecdysis behavior at pupation.

PMID- 7823309
TI  - Pyramidal-cell plasticity in weakly electric fish: a mechanism for attenuating
      responses to reafferent electrosensory inputs.
AB  - Recordings within the posterior eminentia granularis of the weakly electric fish,
      Apteronotus leptorhynchus, revealed multiple types of proprioceptive units
      responsive to changes in the position of the animal's trunk and tail.
      Intracellular labelling showed that the proprioceptor recordings were made from
      axons that ramify extensively within the EGp. The location of the somata giving
      rise to these axons is presently unknown. Electroreceptor afferent responses to
      electric organ discharge amplitude modulations caused by movement of the animal's
      tail were compared to responses caused by electronically generated AMs of similar
      amplitude and time course. These did not differ. Electrosensory lateral line lobe
      pyramidal cells responded significantly less to electric organ discharge
      amplitude modulations caused by changing the animal's posture as compared to
      electronically produced AMs, suggesting that central mechanisms attenuate
      pyramidal cell responses to reafferent electrosensory inputs. Experiments in
      which the pattern of reafferent input associated with changes in posture was
      altered revealed that the pyramidal cells learn, over a time course of several
      minutes, to reject new patterns of input. Both proprioceptive input and
      descending electrosensory input to the posterior eminentia granularis are
      involved in generating the observed plastic changes in pyramidal cell
      responsiveness.

PMID- 7823310
TI  - Photoperiodic activation of fos-like immunoreactive protein in neurones within
      the tuberal hypothalamus of Japanese quail.
AB  - Photoperiodic stimulation of quail (Coturnix coturnix japonica) resulted in the
      appearance of a nuclear fos-like protein within neurones of the basal tuberal
      hypothalamus. On transfer to long days the number of neurones containing this fos
      like immunoreactivity increased from about 150 to 700, the neurones being
      scattered throughout the length of the tubero-infundibular complex. This
      activation had occurred by early in the second long day and was maintained for at
      least three long days. Over this period circulating levels of LH increased seven
      fold, indicating that photoperiodic induction had taken place in the birds. A
      similar time-course of fos-like induction occurred in castrated quail exposed to
      a single long day and then returned to short days. Activation mirrored the long
      term changes in LH secretion found in this paradigm and fos-like immunoreactivity
      showed the same "carry-over" characteristics of photoperiodic induction, being
      maximal two days after the quail had been exposed to the single long day (and
      were again on short days) and when LH secretion was at its maximum. Activation of
      fos-like immunoreactive cells did not take place when long-day quail were
      transferred to short photoperiods. The evidence supports the view that the
      neurones being activated are involved in a specific fashion in the avian
      photoperiodic response.

PMID- 7823311
TI  - Pathways mediating abdominal phasic flexor muscle activity in crayfish with
      chronically cut nerve cords.
AB  - 1. Nerve cord transection abolishes the ability of crayfish (Procambarus clarkii)
      to produce tailflips in response to gradually applied tactile or proprioceptive
      stimulation of the abdomen, but this ability eventually returns. To determine the
      time-course of this return and to analyze its underlying neural pathways, we made
      behavioral observations, electromyographic recordings from abdominal phasic
      flexor muscles, and intracellular recordings from motoneurons in crayfish with
      cord lesions between the thorax and the abdomen. 2. Abdominal stimulation
      activated the phasic flexor muscles in the rostral 5 abdominal segments and their
      homologs in the 6th segment, the posterior telson flexor muscles. Nearly one
      quarter of cord-transfected animals responded to the stimuli with phasic flexor
      muscle activity by one week after the lesion, and almost 90% were responsive by 3
      weeks. 3. Regeneration of axons across the lesion played little or no role in the
      recovery of phasic flexor muscle responsiveness. In addition, the lateral giant
      axons were not activated by the gradually applied stimuli that triggered phasic
      flexor muscle contractions. These results suggest that non-giant pathways
      confined to the abdominal nervous system become functional following chronic cord
      transection. 4. Retransection of the nerve cord below the original lesion showed
      that smaller subsets of the abdominal cord, including a single ganglion, could
      develop the ability to generate phasic flexor muscle contractions in response to
      gradually applied stimuli. 5. Phasic flexor motoneurons in cord-transected
      animals could be excited by stimulation of afferents throughout the abdomen. The
      sensory pathways producing this activation appear to project through the nerve
      cord without much cross-over between left and right sides.

PMID- 7823312
TI  - Outcome measures in rheumatoid arthritis. Introduction.

PMID- 7823315
TI  - Assessment of rheumatoid arthritis--a clinician's viewpoint.
AB  - There are many measures that can be used for the short and longterm monitoring of
      patients with rheumatoid arthritis (RA). An important requirement for such
      assessments is the development of new pharmacologic therapies. It is important to
      assess the need for and the outcome of therapy. In recent years, it has been
      realized that subjective assessments have many advantages over objective ones.
      However, in the majority of cases subjective measures and objective measures
      parallel each other closely. The measurement of acute phase protein, in
      particular C-reactive protein (CRP), is helpful as an indicator of successful
      therapy. From data regarding axial osteoporosis, CRP has been shown to be a
      convenient marker indicating persistent active disease that will produce
      catabolic effects. Dual energy X-ray absorption scans have also been shown to be
      promising in objectively measuring change in the hand for patients with
      inflammatory arthritis. In patients presenting early with RA, it is necessary to
      have accurate indicators. In this respect, genetic predictors have a particular
      value. The most important aspect of the assessment of RA is subjective
      impressions. Therefore, a functional questionnaire such as the health assessment
      questionnaire combined with the objective measure of choice, CRP levels, are the
      assessments of choice.

PMID- 7823313
TI  - Imaging techniques in rheumatoid arthritis.
AB  - Imaging methods have traditionally been the primary tools for documenting disease
      severity and progression. Radiographic methods are insensitive to early changes
      but eventually reflect the degree of bone destruction, cartilage space narrowing,
      and deformity that has occurred. Microfocal radiography is being investigated as
      a method to better define early erosive changes. Neither technique allows optimal
      examination of soft tissues (e.g., joint effusion, pannus, ligaments, and
      tendons). Magnetic resonance imaging (MRI) allows both soft tissues and bones to
      be examined. Articular cartilage imaging is currently under investigation.
      Despite its high cost, the noninvasive nature of MRI and the extensive
      information it provides, make this an exciting area for investigating the changes
      in rheumatoid arthritis and response to therapy.

PMID- 7823314
TI  - Endpoints in rheumatoid arthritis.
AB  - The Outcome Measures in Rheumatoid Arthritis Clinical Trials Conference has
      significantly contributed to the field of clinical outcome measurement. Agreement
      was achieved in designating a preliminary core set of 8 endpoints to be used as a
      minimum in every rheumatoid arthritis (RA) clinical trial of > or = 1 year: acute
      phase reactants, disability, pain, patient global assessment, physician global
      assessment, swollen joint count, tender joint count, and radiographic studies of
      joints. The discussions and nominal group exercises provided a mandate for full
      scale testing of approaches to compare the validity of different assessment
      techniques available for these 8 measures; to determine the minimum level of
      clinical importance for each of the measures; and to refine and validate the
      aggregation of outcome measures into indices, taking special care to ensure
      credibility in the eyes of clinicians, patients, and policy makers. The
      discussions made it clear that to select one intervention definitively over
      another, one must additionally consider outcomes such as drug toxicity, costs,
      and mortality. These aspects need to be explored systematically at subsequent
      conferences.

PMID- 7823316
TI  - Substrate preferences of Vsr DNA mismatch endonuclease and their consequences for
      the evolution of the Escherichia coli K-12 genome.
AB  - The substrate spectrum of Vsr DNA mismatch endonuclease of Escherichia coli K-12
      was investigated using fluorescence-labelled oligonucleotide substrates and a DNA
      sequencer for detection and quantification of substrates and reaction products.
      Fourteen substrates were found to be processed by the enzyme, which differ in one
      or two positions from the canonical pentanucleotide sequence CTA/TGG (T
      mismatched to G). Relative second-order rate constants of these substrates were
      determined in groups of four by multiple substrate kinetics and compared to the
      underresentation of the corresponding pentanucleotides in the E. coli K-12
      genome. The high quality of correlation further establishes active mutagenesis by
      VSP repair as a significant driving force of the evolution of the E. coli K-12
      genome and provides clues to its possible selective value.

PMID- 7823317
TI  - Structure and expression of Euglena gracilis nuclear rbcS genes encoding the
      small subunits of the ribulose 1,5-bisphosphate carboxylase/oxygenase: a novel
      splicing process for unusual intervening sequences?
AB  - In the protist Euglena gracilis, the small subunit of the chloroplast enzyme
      ribulose 1,5-bisphosphate carboxylase/oxygenase is encoded by nuclear rbcS genes
      and synthesized as a polyprotein precursor containing eight mature small subunit
      molecules. This large precursor is encoded by at least eight different nuclear
      genes as ascertained by transcript analysis. The structure of three rbcS genes
      was established and the coding sequences were found to be interrupted by many
      intervening sequences (IVS). Apart from the first 5' intron involved in trans
      splicing, none of these IVSs obeys the GT-AG rule characteristic of introns in
      higher eukaryote genes. Surprisingly, these IVSs are located at identical
      positions within the three genes studied. Moreover, extensive sequence homologies
      were found between IVSs located in the same gene as well as in different genes.
      The sequences of these homologous IVSs differ only by inserted and/or deleted
      sequences. The striking conservation of the 5' and 3' regions of these IVSs is
      correlated to their potential secondary structures. These structures, which bring
      the IVS extremities together with the exon boundaries, could be involved in a
      novel splicing process. The second 5' IVS is shown to be excised before the
      addition of the spliced leader sequence to the pre-mRNA. Similarly, two 3' IVSs
      are excised before the polyadenylation step. These results suggest that IVS
      splicing is faster than eukaryotic genomic cis-splicing and involves components
      other than those of the classical spliceosomes.

PMID- 7823318
TI  - Polymorphic SINEs in chironomids with DNA derived from the R2 insertion site.
AB  - A short interspersed repeat (SINE) in the two sibling species Chironomus
      pallidivittatus and Chironomus tentans is described. It is present at many sites
      in the genome and is surrounded by 10 to 14 bp target site duplications. It
      consists of two sequence modules in different numbers and variable order relative
      to each other and often has large inversions of different sizes at one end. One
      of the modules contains pol III promoter consensus sequences. This SINE,
      nevertheless, is likely to have been dependent on an outside promoter for its
      formation. It is therefore interesting that both modules start with a 22 bp
      region with striking similarity to the R2 insertion site in the preribosomal gene
      of insects. We suggest that this type of SINE, termed Cp1, was formed after a
      series of events among which the first step was the retroposition of a tRNA gene
      into the R2 site in the preribosomal gene by the R2 coded protein. The final step
      is likely to have been due to retroposition from this site.

PMID- 7823319
TI  - Molecular recognition of receptor sites using a genetic algorithm with a
      description of desolvation.
AB  - Understanding the principles whereby macromolecular biological receptors can
      recognise small molecule substrates or inhibitors is the subject of a major
      effort. This is of paramount importance in rational drug design where the
      receptor structure is known (the "docking" problem). Current theoretical
      approaches utilise models of the steric and electrostatic interaction of bound
      ligands and recently conformational flexibility has been incorporated. We report
      results based on software using a genetic algorithm that uses an evolutionary
      strategy in exploring the full conformational flexibility of the ligand with
      partial flexibility of the protein, and which satisfies the fundamental
      requirement that the ligand must displace loosely bound water on binding. Results
      are reported on five test systems showing excellent agreement with experimental
      data. The design of the algorithm offers insight into the molecular recognition
      mechanism.

PMID- 7823320
TI  - The refined structures of goose lysozyme and its complex with a bound
      trisaccharide show that the "goose-type" lysozymes lack a catalytic aspartate
      residue.
AB  - The structure of goose egg-white lysozyme (GEWL) has been refined to an R-value
      of 15.9% at 1.6 A resolution. Details of the structure determination, the
      refinement and the structure itself are presented. The structure of a complex of
      the enzyme with the trisaccharide of N-acetyl glucosamine has also been
      determined and refined at 1.6 A resolution. The trisaccharide occupies sites
      analogous to the B, C and D subsites of chicken (HEWL) and phage T4 (T4L)
      lysozymes. All three lysozymes (GEWL, HEWL and T4L) display the same
      characteristic set of bridging hydrogen bonds between backbone atoms of the
      protein and the 2-acetamido group of the saccharide in subsite C. Glu73 of GEWL
      is seen to correspond closely to Glu35 of HEWL (and to Glu11 of T4L) and supports
      the established view that this group is critically involved in the catalytic
      mechanism. There is, however, no obvious residue in goose lysozyme that is a
      counterpart of Asp52 of chicken lysozyme (or of Asp20 in T4L), suggesting that a
      second acidic residue is not essential for the catalytic activity of goose
      lysozyme, and may not be required for the activity of other lysozymes.

PMID- 7823321
TI  - Non-prolyl cis-trans peptide bond isomerization as a rate-determining step in
      protein unfolding and refolding.
AB  - In wild-type ribonuclease T1 the peptide bond between Tyr38 and Pro39 is in the
      cis conformation. When Pro39 is replaced by an alanine this cis conformation is
      retained, and a non-prolyl cis Tyr38-Ala39 peptide bond is generated. We employed
      a stopped-flow double-mixing technique to investigate the kinetics of the cis-
      >trans isomerization of this peptide bond in the unfolding and the trans-->cis
      isomerization in the refolding of Pro39Ala-ribonuclease T1. In 6.0 M GdmCl (pH
      1.6) and 25 degrees C the protein unfolds rapidly with a time constant of 20 ms,
      followed by Tyr38-Ala39 cis-->trans isomerization. This reaction shows a time
      constant of 730 ms and is about 60-fold faster than the isomerization of the
      Tyr38-Pro39 bond in the wild-type protein. Unfolded molecules with the Tyr38
      Ala39 bond still in the native-like cis conformation accumulate transiently for a
      short time after unfolding is initiated, and they can refold very rapidly to the
      native state with a time constant of 290 ms (in 1.0 M GdmCl, pH 4.6, 25 degrees
      C). After more than three seconds of unfolding virtually all protein molecules
      contain an incorrect trans Tyr38-Ala39 bond and refolding is decelerated
      approximately 1000-fold, because Tyr38-Ala39 trans-->cis re-isomerization is very
      slow and, with its time constant of 480 s, determines the overall rate of
      refolding. Due to the coupling of the cis-trans equilibrium with protein folding
      it was possible to measure the kinetic parameters of the isomerization of a non
      prolyl peptide bond in a protein. Previously this could not be accomplished,
      because the trans isomer is strongly preferred for unsubstituted peptide bonds in
      oligopeptides under virtually all conditions. Our data indicate that the kinetics
      of Tyr38-Pro39 and of Tyr38-Ala39 isomerization differ predominantly in the rate
      of the cis-->trans, rather than of the trans-->cis reaction. The rate of the
      trans-->cis reaction is, however, measured during refolding and may be influenced
      by the formation of ordered protein structure.

PMID- 7823322
TI  - Centromeric dodeca-satellite DNA sequences form fold-back structures.
AB  - The evolutionarily conserved centromeric dodeca-satellite DNA has an asymmetric
      distribution of guanine and cytosine residues resulting in one strand being
      relatively G-rich. This dodeca-satellite G-strand contains a GGGA-tract that is
      similar to the homopurine tracts found in most telomeric DNA sequences. Here, we
      show that the dodeca-satellite G-strand forms intramolecular hairpin structures
      that are stabilized by the formation of non-Watson-Crick G.A pairs as well as
      regular Watson-Crick G.C pairs. Special stacking interactions are also likely to
      contribute significantly to the stability of this structure. This hairpin
      conformation melts at relatively high temperature, around 75 degrees C, and is
      detected under many different ionic and pH conditions. As judged by electron
      microscopy visualization, these structures can be formed in a B-DNA environment.
      Under the same experimental conditions, neither the C-strand nor the double
      stranded dodeca-satellite DNA were found to form any unusual DNA structure. A
      protein activity has been detected that preferentially binds to the single
      stranded dodeca-satellite C-strand. The biological relevance of these results is
      discussed in view of the similarities to telomeric DNA.

PMID- 7823323
TI  - Allyl alcohol cytotoxicity in isolated rat hepatocytes: effects of azide,
      fasting, and fructose.
AB  - The role of altered energy homeostasis in the lethality of allyl alcohol to
      isolated rat hepatocytes was studied. ATP, ADP, AMP, and viability loss (leakage
      of lactate dehydrogenase into the medium) were measured in isolated hepatocytes
      of fed or fasted rats exposed to 0.5 mM allyl alcohol. Adenine mononucleotides
      and cytotoxicity were determined also in hepatocytes incubated with allyl alcohol
      in the presence of 4 mM sodium azide or 15 mM fructose. Allyl alcohol-induced
      cell death in hepatocytes of fed rats was preceded by slight decreases in ATP
      content and energy charge (16% and 12%, respectively). More substantial decreases
      in these parameters occurred in parallel with cell killing, but the effect of
      allyl alcohol on energy status did not exceed the effect produced by a nonlethal
      concentration of sodium azide. Neither azide nor fructose affected the
      development of allyl alcohol cytotoxicity. Moreover, allyl alcohol-induced
      cytotoxicity was similar in hepatocytes of fed and fasted rats. The results
      suggest that altered energy homeostasis is a consequence rather than a cause of
      allyl alcohol-induced hepatocyte lethality.

PMID- 7823324
TI  - Lack of luminal or basolateral uptake and transepithelial transport of mercury in
      isolated perfused proximal tubules exposed to mercury-metallothionein.
AB  - The lumen-to-bath and bath-to-lumen transport, cellular uptake, and toxicity of
      inorganic mercury bound to metallothionein (203Hg-MT) were studied in isolated
      perfused S1, S2, and S3 segments of the renal proximal tubule of rabbits.
      Evidence of very mild toxicity was displayed in some of the segments perfused
      through the lumen with 18.4 microM inorganic mercury in the form of Hg-MT. The
      toxic response was restricted primarily to mild swelling of the epithelial cells
      localized at the end of the tubular segments where the perfusion pipette was
      inserted into the lumen. The cells in the proximal portions of perfused S2
      segments appeared to be most severely affected in that a few blebs would on
      occasion come off the epithelial cells. Mild cellular swelling was also observed
      in some S2 and S3 segments that were exposed to 18.4 microM inorganic mercury in
      the form of Hg-MT in the bath. The swelling was more generalized, involving all
      the epithelial cells along the perfused segment. Very little, or no, measurable
      lumen-to-bath or bath-to-lumen transport of Hg as Hg-MT could be detected in any
      of the 3 perfused segments of the proximal tubule during 40-45 min of perfusion.
      The complex of Hg-MT appeared to behave in a manner similar to that of the volume
      marker [3H]-L-glucose. The lack of tubular transport of Hg as Hg-MT was confirmed
      by little or no measurable uptake and accumulation of inorganic mercury in the
      tubular epithelial cells. Thus, our findings indicate that the Hg-MT complex is
      not taken up avidly in isolated perfused S1, S2, or S3 segments of the proximal
      tubule.

PMID- 7823325
TI  - Incubation temperature as a modifying factor on survival of Tenebrio molitor
      reared in selenium-containing media.
AB  - Newly emerged Tenebrio molitor were reared at 4, 25, and 37 degrees C in nutrient
      media supplemented with sodium selenate (0.0125, 0.0200, 0.0500, and 0.1000%).
      Ten insects comprised each group. Controls were maintained in unsupplemented
      medium at the same temperatures as the experimental groups. Survival percentages
      were determined. Survival curves were estimated at given times postincubation.
      Controls at 4 and 37 degrees C showed an increased lethality compared to those
      insects at 25 degrees C. Data indicate that 4 degrees C had a protective effect
      on survival for insects reared in media containing the three highest
      concentrations of selenium. For insects at 37 degrees C, killing was striking and
      equivalent for all groups, irrespective of media supplementation.

PMID- 7823326
TI  - Designing a biological monitoring program to assess community exposure to
      chromium.

PMID- 7823327
TI  - Designing a biological monitoring program to assess community exposure to
      chromium.

PMID- 7823329
TI  - Role of retinal metabolism in methanol-induced retinal toxicity.
AB  - Methanol is a toxicant that causes systemic and ocular toxicity after acute
      exposure. The folate-reduced (FR) rat is an excellent animal model that mimics
      characteristic human methanol toxic responses. The present study examines the
      role of the methanol metabolites formaldehyde and formate in the initiation of
      methanol-induced retinal toxicity. After a single oral dose of 3.0 g/kg methanol,
      blood methanol concentrations were not significantly different in FR rats
      compared with folate-sufficient (FS) (control) rats. However, FR rats treated
      with 3.0 g/kg methanol displayed elevated blood (14.6 mM) and vitreous humor
      (19.5 mM) formate levels and abnormal electroretinograms (loss of b-wave) 48 h
      postdose. FR rats pretreated with disulfiram (DSF) prior to 3.0 g/kg methanol
      treatment failed to display these symptoms. Formaldehyde was not detected in
      blood or vitreous humor with or without DSF treatment, suggesting that formate is
      the toxic metabolite in methanol-induced retinal toxicity. Additionally, creating
      a blood formate profile (14.2 mM at 48 h) similar to that observed in methanol
      treated rats by iv infusion of pH-buffered formate does not alter the
      electroretinogram as is observed with methanol treatment. These data suggest that
      intraretinal metabolism of methanol is necessary for the formate-mediated
      initiation of methanol-induced retinal toxicity.

PMID- 7823328
TI  - Effect of oral dosing vehicles on the subchronic hepatotoxicity of carbon
      tetrachloride in the rat.
AB  - Previous studies in this laboratory have shown that corn oil delayed and
      prolonged the gastrointestinal absorption of carbon tetrachloride (CCl4) and
      reduced its acute hepatotoxicity in rats. The objective of the present study was
      to extend the duration of ingestion of CCl4 to assess vehicle effects on the
      subchronic oral toxicity of CCl4. Male Harlan Sprague-Dawley rats were given
      doses of 0, 25, or 100 mg CCl4/kg body weight by gavage in either corn oil or a
      1% Emulphor aqueous emulsion 5 times a week for 13 wk. Blood was collected at 4,
      8, and 13 wk for measurement of serum enzymes. Liver samples were also taken at
      13 wk for measurement of triglyceride and microsomal enzyme levels, as well as
      for histopathological examination. Serum enzyme levels peaked at 8 wk in the high
      dose groups, but not until 13 wk in the low-dose animals. Effects of CCl4 on
      serum and microsomal enzymes were of similar magnitude in the two vehicle groups.
      A comprehensive histopathological examination revealed no qualitative or
      quantitative differences between the corn oil and aqueous vehicle groups in
      hepatic lesions. Although CCl4 and chloroform have been reported by other
      investigators to be more hepatotoxic to mice when given for 90 d in corn oil,
      current findings indicate that corn oil does not significantly alter the
      subchronic hepatotoxicity of CCl4 in rats from that when the halocarbon is given
      in an aqueous medium.

PMID- 7823331
TI  - Acrylamide arrests mitosis and prevents chromosome migration in the absence of
      changes in spindle microtubules.
AB  - Cultured HT 1080 fibrosarcoma cells were exposed to acrylamide (ACR), an
      industrial neurotoxicant that disrupts neuronal intracellular transport, to
      determine if mitosis (another microtubule-based intracellular transport system)
      was adversely affected. The number of cells arrested in mitosis increased, in a
      concentration-dependent manner, from 1 to 10 mM acrylamide. A 4-h exposure to 10
      mM acrylamide increased the mitotic index by 4.5-fold over control, comparable to
      the arrest caused by colchicine. In mitotic acrylamide-exposed cells, the
      chromosomes remained at the metaphase plate; no changes in spindle microtubules
      (MTs), as seen with tubulin immunofluorescence, were observed. The distance
      between spindle poles (interaster) was the same in control and experimental
      cells. The non-neurotoxic analogue methylene bisacrylamide had no effect in the
      same concentration range. The data suggest potential molecular mechanisms of
      action for general toxicity and neurotoxicity to be disruption in MT disassembly
      or MT-kinetochore interactions and/or cellular homeostasis.

PMID- 7823330
TI  - Dual effect of nitrogen dioxide on barrier properties of guinea pig
      tracheobronchial epithelial monolayers cultured in an air interface.
AB  - Nitrogen dioxide (NO2) is an oxidant gas that may injure the airway epithelial
      lining, leading to decrements in barrier and active ion transport properties. The
      present studies examined alterations of bioelectric properties and solute flux by
      guinea pig tracheobronchial epithelial (GPTE) monolayers exposed in vitro to NO2.
      Confluent GPTE monolayers were exposed to NO2 levels between 0.5 and 5 ppm, while
      controls were exposed to air. Following exposure, monolayers were mounted in
      Ussing chambers for measurement of transepithelial resistance (Rte) and short
      circuit current (SCC). A 1-h exposure to 1 ppm NO2 significantly increased SCC to
      131.3 +/- 8.7% of air controls, while Rte with a value of 109.3 +/- 13.8% was
      unchanged. In contrast, a 1-h exposure to 2 or 5 ppm NO2 significantly decreased
      Rte to 39.0 +/- 1.6 or 35.5 +/- 7.3% of air controls, respectively, while SCC
      values of 140.3 +/- 10.4 or 153.3 +/- 8.6%, respectively, were also significantly
      elevated. A 1-h exposure to 2 or 5 ppm NO2 significantly increased sucrose
      permeability across GPTE monolayers to 446.8 +/- 117 or 313.3 +/- 39.5% of air
      controls, respectively, while glycerol permeability was unchanged. In contrast, a
      1-h exposure to 1 ppm NO2 produced no alterations of sucrose or glycerol flux.
      The SCC of control GPTE monolayers (1-h air exposure) consisted of 50% bumetanide
      sensitive and 40% amiloride-sensitive current; exposure for 1 h to 2 ppm NO2 led
      to no changes in the corresponding SCC components. Active ion transport (i.e.,
      SCC) across the airway epithelium was significantly increased after exposure to
      NO2 levels < or = 1 ppm with no change of paracellular pathways for diffusion,
      suggesting that this reactive gas alters cell membrane function. The increased
      SCC may lead to impairment of fluid balance and mucociliary clearance. NO2
      mediated tissue injury with levels > or = 2 ppm primarily affects passive airway
      epithelial barrier functions, probably by altering tight junctions, which could
      result in increased transepithelial solute and fluid leakage in vivo.

PMID- 7823332
TI  - In vivo and in vitro efficacy of a new carbodithioate for the mobilization of
      cadmium.
AB  - Female Wistar rats with chronic cadmium intoxication (oral exposure to low
      dosages of CdCl2 in drinking water over a period of 90 d) were used to examine
      the in vivo ability of a newly developed chelator, sodium N-(4-methylbenzyl)-4-O
      (beta-D-galactopyranosyl)-D-glucamine-N- carbodithioate (MeBLDTC), singly and in
      combination with sodium 4-carboxy-amidopiperidine-N-carbodithioate (INADTC) as
      agents to induce the biliary and urinary excretion of cadmium. The combined
      administration of the two dithiocarbamates, which differ greatly in molecular
      weight and structural features, led to a synergistic increase in the biliary
      excretion of cadmium and an enhanced reduction of renal cadmium levels. The use
      of such a coadministration produced an increase in the biliary excretion of
      cadmium that was more than double that expected if the compounds acted in an
      additive fashion. Such mixed-chelation therapy has potential utility in the
      treatment of human chronic cadmium intoxication. The hepatocytes isolated from
      chronically Cd-intoxicated rats were used as an in vitro screening model system
      for the new chelator. The plasma membrane integrity study with MeBLDTC at 0.48
      mmol/20 ml of hepatocyte incubate using the trypan blue exclusion test and
      lactate dehydrogenase (LDH) leakage test revealed no differences in the cell
      viability with or without chelator. The cellular metabolic competence measured as
      the rate of urea synthesis also did not show any marked deviation from that of
      controls when incubated with MeBLDTC at three different concentrations. In the
      hepatocyte cultures, MeBLDTC induced a significant removal of cadmium from the
      hepatocytes at concentrations as low as 0.04 mmol/20 ml.

PMID- 7823333
TI  - Oversaturation of color may obscure small intraluminal partial occlusions in
      color Doppler imaging.
AB  - Color Doppler imaging has been reported to have a low degree of accuracy in
      diagnosing nonocclusive deep venous thrombosis. In this modality the color
      saturation while diagnosing deep vein thrombosis depends on the blood flow
      velocity and the sensitivity setting of the color image. To determine the effect
      of color saturation on the detection of thrombi, an in vitro experiment was
      performed using a closed-loop tube circulation system with a simulated small
      intraluminal partial occlusion. Heparinized blood was circulated at three
      different velocities (2, 5.5, and 9 cm/sec) and the vessels were scanned
      longitudinally and transversely with color Doppler imaging at three color
      sensitivity settings (low, medium, and high sensitivity). In appropriate color
      sensitivity settings (i.e., the low, medium, and high sensitivity for the
      velocity of 9,5.5 and 2 cm/sec, respectively), the color was saturated adequately
      in the tube lumen so that the partial occlusion was delineated as a color filling
      defect in the color field. In undersaturated color conditions, the partial
      occlusion was depicted owing to its echogenicity, but not as a color filling
      defect. In over-saturated color conditions, such as the high color sensitivity at
      the high velocity, the partial occlusion was obscured by the excessive amount of
      color. The over saturation of color may be one of the reasons color Doppler
      imaging fails to detect deep vein thrombosis, particularly small intraluminal
      thrombi.

PMID- 7823334
TI  - Discordant umbilical cord structure in a twin gestation.

PMID- 7823335
TI  - Prenatal detection of severe right ventricular outflow tract obstruction:
      pulmonary stenosis and pulmonary atresia.

PMID- 7823336
TI  - Gastrointestinal inflammation in children: color Doppler ultrasonography.
AB  - We conducted this study to determine if color Doppler ultrasonography can
      identify increased vascularity associated with gastrointestinal inflammatory
      conditions and to determine if specific diagnoses can be established based on
      flow patterns. Twenty-five children with acute right lower quadrant pain and
      discharge diagnoses of inflammatory bowel processes were examined by color
      Doppler sonography, as an adjunct to routine gray-scale examinations. Final
      diagnoses included gastroenteritis (10 cases), Crohn's disease (five cases),
      neutropenic colitis (four cases), peritonitis (four cases), and Yersinia
      enterocolitis (two cases). The results of color Doppler sonography were
      considered positive for inflammation if increased vascularity was demonstrated in
      the bowel mucosa, muscularis layer, or adjacent tissues. A control group of 19
      patients was examined. No sonographic abnormalities were identified in any
      patients in the control group. Diffuse, concentric wall thickening with increased
      blood flow centrally within the mucosa was seen in Crohn's disease (60%) and
      Yersinia enterocolitis (100%), whereas wall thickening with increased transmural
      vascularity was identified in neutropenic colitis (50%) and Crohn's disease
      (40%). In contrast, in peritonitis color Doppler sonography showed thickened
      bowel wall and hypervascularity within peripheral bowel wall or in adjacent soft
      tissues. No demonstrable bowel vascularity was seen in gastroenteritis. Our
      experience suggests that mucosal or transmural hypervascularity on color Doppler
      sonography can be seen with several inflammatory bowel processes, but it is
      nonspecific. However, color Doppler sonography may aid in differentiating primary
      bowel disease from extrinsic inflammatory conditions, such as peritonitis.

PMID- 7823337
TI  - Comparative study of transvaginal sonography and hysteroscopy for the detection
      of pathologic endometrial lesions in women with postmenopausal bleeding.
AB  - Dilatation and curettage is used as the "gold standard" for diagnosing pathologic
      endometrial lesions in women with postmenopausal bleeding. In this group of
      women, about 10% have an endometrial cancer and an additional 20% have some other
      endometrial abnormality. However, some abnormalities, such as endometrial polyps
      and submucous fibroids, are difficult to diagnose by dilatation and curettage. In
      such cases, combining transvaginal sonography with hysteroscopy may be of value.
      This study compared the use of transvaginal sonography and hysteroscopy for
      evaluation of the uterine cavity in women with postmenopausal bleeding. The study
      included 51 women, 39 of whom had an abnormally thick ( > 4 mm) endometrium as
      measured by transvaginal sonography, and 35 of 39 had an abnormal appearance at
      hysteroscopy. The sensitivity and specificity for the measurement of endometrial
      thickness using transvaginal sonography to diagnose an endometrial abnormality
      were 100% and 75%, respectively. The corresponding figures for hysteroscopy were
      97% and 88%. In all women with an endometrial thickness of 8 mm as measured by
      transvaginal sonography, hysteroscopy is identified as an abnormality. The study
      indicates that transvaginal sonography reveals an endometrial thickness of > or =
      8 mm and the histopathologic diagnosis after dilatation and curettage is atrophic
      endometrial polyp or submucous myoma.

PMID- 7823338
TI  - Transverse umbilical arterial diameter: technique for the prenatal diagnosis of
      single umbilical artery.
AB  - We investigated the relationship between the transverse umbilical arterial
      diameter and the presence of a single umbilical artery. Further, we speculated
      that fetal physiologic and hemodynamic limitations in pregnancies complicated by
      a single umbilical artery would result in larger umbilical arterial diameters
      than the typical three-vessel cord. The identification of a sufficiently large
      umbilical artery may be pathognomonic for single umbilical artery. The transverse
      umbilical arterial diameter was obtained in 100 consecutive, uncomplicated
      singleton pregnancies between 20 and 38 weeks' gestation. These measurements were
      compared with the transverse umbilical arterial diameter of 23 pregnancies in
      which a single umbilical artery was identified with ultrasonography and postnatal
      examination. Transverse umbilical arterial diameter measurements of the two
      groups were compared. Before 36 weeks' gestation, all pregnancies with a single
      umbilical artery had a transverse umbilical arterial diameter measurement > 4 mm
      and all pregnancies with two umbilical arteries had a transverse umbilical
      arterial diameter measurement < or = 4 mm. Because oligohydramnios, multiple
      pregnancy, or suboptimal cord position may obscure the expeditious identification
      of the number of umbilical cord vessels, measurement of the transverse umbilical
      arterial diameter may prove useful in the identification of single umbilical
      artery. On the basis of this preliminary evaluation, we suggest that a transverse
      umbilical arterial diameter measurement > 4 mm is predictive of single umbilical
      artery between 20 and 36 weeks' gestation.

PMID- 7823339
TI  - Nephrocalcinosis in very low birth weight neonates: sonographic patterns,
      histologic characteristics, and clinical risk factors.
AB  - Fifty infants weighing less than 1200 grams at birth who survived at least 3
      weeks were enrolled in this study, of whom 14 (28%) developed sonographic
      evidence of nephrocalcinosis by 9 weeks, despite median total furosemide dose of
      only 2 mg/kg. Risk factors for development of neonatal nephrocalcinosis were
      white race (P < 0.01) and positive family history of kidney stones (P < 0.001).
      Sonography demonstrated echogenic foci measuring 2 to 9 mm near the papillary
      tips in most infants with nephrocalcinosis even though the kidneys apparently had
      not progressed through the stages of diffuse medullary echogenicity that
      Patriquin and Robitaille postulated are the sonographic correlates of the
      Anderson-Carr-Randall progression, a leading theory of renal calculus formation.
      The presence of intratubular calcifications in the two patients studied post
      mortem also is contrary to the Anderson-Carr-Randall theories that center on
      interstitial calcium deposition. Although neonatal nephrocalcinosis shares some
      clinical risk factors (white race and positive family history of renal calculi)
      with renal calcium deposition in older children and adults, the prevalent
      theories of renal calcium deposition do not account for its sonographic or
      histologic manifestations.

PMID- 7823340
TI  - Transvaginal echocardiographic examination of the fetal heart between 13 and 15
      weeks' gestation in a low-risk population.
AB  - The object of our investigation was to evaluate the potential of transvaginal
      echocardiography for a complete anatomic study of the fetal heart, and for
      detection of congenital heart diseases in low-risk pregnant patients between 13
      and 15 weeks' gestation. High-frequency (6.5 MHz and 7.5 MHz) transvaginal probes
      were employed for fetal echocardiographic assessment. Six hundred and sixty
      patients considered at low risk for congenital heart disease underwent in utero
      ultrasonographic studies, neonatal records, postnatal imaging studies, and
      pathologic examination. The four-chamber view was obtained in 100% of the
      fetuses, while the extended fetal heart examination was completed in 98%. Six
      fetuses with cardiac defects were diagnosed during the study: three had major
      heart defects (aortic atresia, tetralogy of Fallot, and persistent truncus
      arteriosus), all detected at the early transvaginal scan; three cardiac anomalies
      escaped our early diagnosis; two fetuses had a minor ventricular septal defect
      diagnosed only postnatally; and one had multiple cardiac rhabdomyoma diagnosed in
      the third trimester. Our results demonstrate that between 13 and 15 weeks'
      gestation transvaginal echocardiographic assessment of the fetal heart in the low
      risk population is feasible. Moreover, some severe anomalies may be detected at
      such an early gestational age.

PMID- 7823341
TI  - Doppler analysis of hemodialysis grafts: resistive index as a predictor of
      stenosis.
AB  - A series of six hemodialysis vascular access patients was evaluated with duplex
      Doppler sonography and angiography to identify Doppler sonographic parameters
      that are predictors of venous outflow stenosis. This preliminary series indicates
      that no venous outflow stenosis was present angiographically when the resistive
      index gradient across the venous anastomosis is less than or equal to zero and a
      significant venous outflow stenosis (50 to 100%) was present when the resistive
      index gradient is 0.15 or greater (P = 0.002, r = 0.963). Doppler acquisition of
      resistive index gradients across regions of venous outflow is a promising,
      noninvasive means of rapid radiologic evaluation of hemodialysis graft patients,
      especially when the need for angiography is equivocal.

PMID- 7823342
TI  - Technique for detecting and evaluating breast lesions.
AB  - A sonographic method is described that provides additional information concerning
      ultrasonic tissue properties. It allows simplified interpretation and eventually
      might permit automatization. In this technique a totally reflecting plate is used
      as an indicator for presence of breast lesions because such lesions cause changes
      of reflectivity, attenuation, and velocity when exposed to ultrasound beams.
      Twenty-seven benign lesions and 33 malignancies were examined with this method.

PMID- 7823343
TI  - Tarlov cysts: a cause of complex bilateral adnexal masses on pelvic sonography.

PMID- 7823344
TI  - Dividing membrane may not always be helpful in determining placental chorionicity
      in twin gestations.

PMID- 7823345
TI  - Prenatal sonographic diagnosis of intermembranous abruptio placentae in a twin
      pregnancy.

PMID- 7823346
TI  - Primary cervicovaginal endometriosis: sonographic findings with MR imaging
      correlation.

PMID- 7823347
TI  - Fetal cardiac rhabdomyomas presenting as diffuse myocardial thickening.

PMID- 7823348
TI  - Color Doppler ultrasonographic findings in low and high grade endometrial stromal
      sarcomas.

PMID- 7823349
TI  - The clinical and hemodynamic results after axillary-to-popliteal vein valve
      transplantation.
AB  - PURPOSE: To evaluate the results of axillary vein to popliteal vein valve
      transplantation (VVTX), we reviewed the clinical, phlebographic, and noninvasive
      hemodynamic results in 15 patients. METHODS: All patients had postthrombotic
      destruction of deep venous valves as determined by ascending phlebography,
      whereas descending phlebography demonstrated grade III or IV reflux in all
      patients. A segment of valve-bearing axillary vein was transplanted to the
      popliteal vein in the affected limb. Postoperative evaluation was by clinical,
      noninvasive, and phlebographic means. RESULTS: Over a mean follow-up period of
      5.3 years (1.25 to 11 years), 13 of 14 patients (93%) had symptomatic improvement
      with relief of swelling, whereas all 14 patients who were admitted with pain had
      relief after operation. Thirteen of 15 patients (87%) returned to work or
      household duties. Physical findings of edema, skin pigmentation, and
      lipodermatosclerosis improved in most patients. Only three patients (21%) had
      development of recurrent ulcers, with an average postoperative ulcer-free
      interval of 4 years by life-table analysis. The cumulative ulcer-free survival
      rate for the group averaged 62% at late follow-up. All three patients with ulcer
      recurrence had a functioning valve by descending phlebography, but recurrent
      perforating veins were found in two patients, and deep venous thrombosis above a
      patent VVTX was observed in the third. Late assessment of reflux by venous
      filling index and valve closure times for the entire sample demonstrated mean
      values of 4.9 seconds in the latter and 6.8 ml/sec in the former. Residual volume
      fraction, which correlates with invasive ambulatory venous pressures, was reduced
      to a mean of 31%. No deterioration in late sequential noninvasive values could be
      detected. CONCLUSION: VVTX is a durable procedure for preventing recurrent venous
      ulcers.

PMID- 7823350
TI  - Clinical outcome in patients with mild and moderate carotid artery stenosis.
AB  - PURPOSE: The natural history of incidentally discovered asymptomatic mild (< 50%)
      and moderate (50% to 79%) carotid artery stenosis is not known. The carotid
      artery duplex ultrasound surveillance program at the University of Washington
      Department of Vascular Surgery has serially evaluated patients with carotid
      artery disease for more than a decade and provides data on the progress and
      management of this disease. METHODS: Patients with asymptomatic carotid artery
      bruits who had carotid artery disease causing less than 80% lumen diameter
      narrowing at their initial visit were identified. At each return visit (6 months,
      1 year, and annually thereafter) a clinical questionnaire was completed, and
      bilateral carotid artery duplex sonography was performed. RESULTS: Two hundred
      thirty-two patients (136 men and 96 women) were monitored for up to 10 years with
      sufficient data for a 7-year life-table analysis. Progression in the degree of
      stenosis was noted in 23% of patients during follow-up, and nearly half of these
      progressed to severe stenosis (80% to 99%) or occlusion. The risk of progression
      to severe stenosis and occlusion was significantly greater for those patients
      with moderate initial stenosis than mild initial stenosis (p < 0.01). The
      cumulative stroke risk for patients with mild initial stenosis (6%) was half of
      that for patients with moderate initial stenosis (11%) after 7 years. Carotid
      endarterectomy was performed in 27 patients during follow-up; in 13 the
      indication was an event ipsilateral to the stenosis, and in 14 there was
      asymptomatic progression to high-grade stenosis. CONCLUSIONS: Regular monitoring
      of mild to moderate carotid artery stenosis shows how these lesions progress over
      time, permitting a realistic appraisal of their potential for producing an
      ischemic cerebrovascular event.

PMID- 7823351
TI  - Femorodistal vein grafts: the utility of graft surveillance criteria.
AB  - PURPOSE: This retrospective review of femorodistal vein grafts was analyzed to
      determine the usefulness of various graft surveillance criteria. METHOD: The
      surveillance schedule involved evaluations at 1 month, every 3 months the first
      year, and then every 6 months. Salvage intervention or graft occlusion occurring
      within the next follow-up interval defined surveillance end points. One hundred
      two grafts (329 surveillance visits) had an ankle/brachial index (ABI). A duplex
      scanning-determined midgraft peak systolic flow velocity (PSFV) was available for
      81 grafts (262 visits). Forty-eight grafts (137 visits) had both a PSFV and
      entire graft duplex scanning (EGDS) to determine stenosis greater than 50%,
      whereas 40 grafts (91 visits) had simultaneous ABI and EGDS. RESULTS: When a
      greater than 15% decrease in ABI denoted an abnormal surveillance study result, a
      positive predictive value (PPV) of 24.3% and negative predictive value of 94.5%
      were noted. Similarly, a PSFV cutoff of less than 35 cm/sec demonstrated values
      of 26.3% and 94.2%, respectively. When an EGDS of greater than 50% stenosis or a
      PSFV of less than 35 cm/sec were the cutoff criteria, the PPV was 36.7% and
      negative predictive value 99.1%, whereas characterizing abnormal results further
      with ABI (> 15% decreases) increased the PPV to 83.3%. CONCLUSION: The
      combination of an EGDS, midgraft PSFV, and ABI provides optimal follow-up for our
      patients with a femorodistal vein graft.

PMID- 7823352
TI  - Luminal surface concentration of lipoprotein (LDL) and its effect on the wall
      uptake of cholesterol by canine carotid arteries.
AB  - PURPOSE: The effect of near-wall blood flow velocity and plasma filtration
      velocity across the arterial wall on luminal surface concentration of low-density
      lipoproteins (LDL) and the uptake of tritium-cholesterol were investigated.
      METHODS: A numeric analysis of LDL transport in steady flow, over the range of
      physiologically relevant flow rates, predicted a surface concentration of LDL of
      4% to 16% greater than that in the bulk flow. The LDL surface concentration
      increased linearly with filtration velocity and inversely with wall shear rate.
      RESULTS: These were validated experimentally in canine carotid arteries. When the
      transmural pressure was increased from 100 to 200 mm Hg, the filtration velocity
      increased from 5.13 x 10(-6) cm/sec to 8.41 x 10(-6) cm/sec, whereas the
      normalized uptake rate of tritium-cholesterol increased from 3.58 x 10(-4)
      cm/hour to 7.36 x 10(-4) cm/hour. CONCLUSION: These results indicate that lipids
      accumulate at the luminal surface in areas where blood flow velocity and wall
      shear stress are low and where the permeability of the endothelial layer is
      enhanced. Moreover, the rate of lipid infiltration into the blood vessel walls is
      affected by the luminal surface concentration. These findings are consistent with
      chronic hypertension and elevated blood cholesterol concentrations being major
      risk factors for atherosclerosis.

PMID- 7823353
TI  - Asymptomatic carotid artery stenosis and stroke in patients undergoing
      cardiopulmonary bypass.
AB  - PURPOSE: This study was undertaken to assess the natural history of carotid
      artery stenosis in patients undergoing cardiopulmonary bypass (CPB) at a Veterans
      Administration Medical Center. METHODS: Between January 1989 and August 1993, all
      patients undergoing CPB were offered preoperative carotid artery ultrasound
      screening as part of an investigative protocol. Patients were monitored in
      hospital for the occurrence of perioperative neurologic deficit. RESULTS: A total
      of 582 patients underwent carotid artery ultrasound screening. Greater than 50%
      stenosis or occlusion of one or both internal carotid arteries was present in 130
      patients (22%), with 80% or greater stenosis or occlusion of one or both arteries
      present in 70 patients (12%). In-hospital stroke or death occurred in 12 (2.1%)
      and 36 (6.2%) patients, respectively. Of the 12 strokes, five were global and
      seven were hemispheric in distribution. Of the five patients who had global
      events, none had evidence of carotid artery stenosis. However, of the seven
      patients who had hemispheric events, five had significant 50% or greater stenosis
      or occlusion of the internal carotid artery ipsilateral to the hemispheric
      stroke. Therefore the presence of carotid artery stenosis or occlusion was
      significantly associated with hemispheric stroke (no stenosis 0.34% vs stenosis
      3.8%; p = 0.0072). Furthermore, the risk of hemispheric stroke in patients with
      unilateral 80% to 99% stenosis, bilateral 50% to 99% stenosis, or unilateral
      occlusion with contralateral 50% or greater stenosis was 5.3% (4 of 75). No
      strokes occurred in patients with unilateral 50% to 79% stenosis (n = 52).
      CONCLUSIONS: It is concluded that carotid atherosclerosis is a risk factor for
      hemispheric stroke in patients undergoing CPB.

PMID- 7823354
TI  - Carotid artery duplex scanning in preoperative assessment for coronary artery
      revascularization: the association between peripheral vascular disease, carotid
      artery stenosis, and stroke.
AB  - PURPOSE: The purpose of this study was to identify high-risk populations for
      severe carotid artery disease (SCD) and neurologic events (NE) after nonemergency
      isolated coronary artery bypass graft procedures (CABG). METHODS: Between
      February 1989 and July 1992, 387 patients underwent preoperative carotid artery
      duplex scanning as part of a preoperative assessment for nonemergency cardiac
      procedures. Of these patients, 376 had isolated CABG, and 11 had combined carotid
      endarterectomy (CEA) and CABG. Patient demographics, risk factors, and
      preoperative neurologic symptoms were recorded and analyzed. Severe carotid
      artery disease was defined as a 80% or greater stenosis of either internal
      carotid artery by carotid artery duplex scanning. Patients were evaluated for
      neurologic events (cerebrovascular accident, transient ischemic attack, amaurosis
      fugax, or reversible ischemic neurologic deficits) during the in-hospital
      postoperative period. RESULTS: The prevalence of SCD was 8.5% (33 patients). The
      33 patients with SCD were significantly older (65.6 +/- 6.5 years vs 62.5 +/-
      10.4 years, p = 0.02), had previous CEA (27.3% vs 2.0%, p = 0.00001), had
      preoperative neurologic symptoms (21.2% vs 5.9%, p = 0.002), and had peripheral
      vascular disease (PVD) (63.6% vs 16.9%, p = 0.00001). The sensitivity of PVD for
      SCD is 63.6% (n = 21/33) (specificity 83.1%, positive predictive value 25.9%,
      negative predictive value 96.1%). In patients undergoing CABG alone, those who
      had postoperative NE were older (69.6 +/- 6.7 years vs 62.5 +/- 10.3 years, p =
      0.036) and more likely to have PVD (50% vs 19.7%, p = 0.034), SCD (40% vs 4.9%, p
      = 0.001) and previous CEA (40% vs 2.7%, p = 0.0002). The incidence of
      postoperative NE in patients with SCD was 18.2% vs 1.7% in patients without SCD
      (p = 0.001). The sensitivity of SCD for NE was 40% (n = 4/10) (specificity 95.1%,
      positive predictive value 18.2%, negative predictive value 98.3%). CONCLUSIONS:
      PVD may be helpful to identify patients at high risk for severe carotid artery
      stenosis. Postoperative NE in patients with CABG are associated with increasing
      age, carotid artery stenosis greater than 80%, previous CEA, and PVD.

PMID- 7823355
TI  - The origin of infrainguinal vein graft stenosis: a prospective study based on
      duplex surveillance.
AB  - PURPOSE: The purpose of this study was to determine the origin of vein graft
      lesions and their propensity for progression based on prospective duplex
      surveillance of 135 infrainguinal vein bypasses. METHODS: One hundred sixteen
      greater saphenous, 13 spliced, five cephalic, and one superficial femoral vein
      grafts were evaluated by color duplex imaging at surgical procedure, 1 and 6
      weeks, 3 and 6 months, and every 3 to 6 months thereafter. Duplex-identified
      lesions were graded by peak systolic velocity and velocity ratio criteria and
      were either followed or subjected to revision. RESULTS: Early postoperative
      duplex surveillance allowed stratification of infrainguinal grafts into two
      subsets. Of 91 (67%) grafts with normal early scans (at 3 months), only two
      (2.2%) developed de novo stenoses (at 6 and 8 months) that required revision.
      Forty-four grafts with abnormal duplex scans had a focal flow abnormality (peak
      systolic velocity > 150 cm/sec, velocity ratio > 1.5) in the graft body (n = 24)
      or anastomotic region (n = 20). In 14 grafts the flow abnormality (mean peak
      systolic velocity = 217 cm/sec, velocity ratio = 2.3) normalized. Ten additional
      grafts exhibited a moderate, persistent graft stenosis (mean peak systolic
      velocity 248 cm/sec, velocity ratio = 3.3) that was not repaired. All 20 grafts
      with lesions that progressed to high-grade stenosis (mean peak systolic velocity
      = 362 cm/sec, velocity ratio = 7.2) and were revised had a residual flow
      abnormality confirmed at operation, or it appeared by 6 weeks. In the entire
      series six (4.4%) grafts failed during the mean 12-month follow-up interval
      (range 3 to 30 months), 4 with unrepaired defects and two after revision.
      CONCLUSIONS: Prospective duplex surveillance verified that de novo graft stenosis
      was uncommon (< 2.2%) after reversed and in situ saphenous vein bypass grafting.
      Graft stenoses developed at sites of unrepaired defects or early appearing
      conduit abnormalities. An early appearing duplex focal flow abnormality warranted
      careful surveillance, because one half of such sites progressed to a high-grade
      stenosis. Grafts with normal early duplex scans exhibited a low incidence of
      stenosis development or occlusion, and thus less intense postoperative
      surveillance can be recommended.

PMID- 7823356
TI  - What you did not know about the North American Symptomatic Carotid Endarterectomy
      Trial.

PMID- 7823358
TI  - A useful modification of the Potts-Smith scissors.

PMID- 7823357
TI  - Portal vein replacement by a synthetic graft in hepatic resection.

PMID- 7823359
TI  - Femoropopliteal-crural graft patency is improved by an intensive surveillance
      program: a prospective randomized study.
AB  - PURPOSE: The purpose of this study was to evaluate whether intensive surveillance
      compared with routine follow-up examinations improves femoropopliteal/crural
      graft patency. METHODS: After operation the patients were randomized to intensive
      (n = 79) or routine surveillance (n = 77). The groups were matched with regard to
      sex, diabetes, indication for surgical procedure, surgical procedure, and graft
      material. Intensive surveillance was clinical examination, ankle/brachial index
      measurements, and duplex scans 1, 3, 6, 9, 12, 15, 18, 21, 24, and 36 months
      after operation. Routine surveillance was clinical examination and ankle/brachial
      index measurements without duplex scanning 1, 12, 24, and 36 months after
      operation. Grafts with a decrease in ankle/brachial index of more than 0.15
      compared with the initial postoperative ankle/brachial index or a duplex scan
      showing a graft or anastomotic stenosis of more than 50% underwent angiography
      and if necessary, a revision or repeat procedure. Occluded grafts were reopened
      with thrombectomy or thrombolysis or were replaced with a new graft. RESULTS:
      Assisted primary cumulative vein graft patency in the intensive group (n = 56)
      compared with that in the routine surveillance group (n = 50) after 3 years was
      78% versus 53% (chi square analysis, 4.51; one degree of freedom; p < 0.05).
      Secondary patency was 82% versus 56% (chi square analysis, 5.62; one degree of
      freedom; p < 0.05). Assisted primary cumulative e-polytetrafluoroethylene and
      composite graft patency after 1 year in the intensive group (n = 23) compared
      with that of the routine surveillance group (n = 20) was 57% vs 50% (chi square
      analysis, 2.17; one degree of freedom; p > 0.1). Secondary patency was 67% vs 54%
      (chi square analysis, 1.85; one degree of freedom; p > 0.1). Revisions were made
      on 14 patent and 10 thrombosed grafts in the intensive group and on four patent
      and 15 thrombosed grafts in the routine surveillance group. All except eight were
      made during the first postoperative year. CONCLUSIONS: Intensive surveillance
      identified failing vein grafts leading to a significantly higher cumulative
      assisted primary and secondary patency compared with cumulative assisted primary
      and secondary patency after routine follow-up examination. The patency of e
      polytetrafluoroethylene and composite grafts was not influenced by intensive
      surveillance.

PMID- 7823360
TI  - Return to well-being and function after infrainguinal revascularization.
AB  - PURPOSE: The purpose of this study was to assess functional status, well-being,
      and symptom relief of patients after infrainguinal revascularization for severe
      peripheral vascular disease. METHODS: Two questionnaires were used to assess
      symptoms, functional status, and well-being before operation and 6 months after
      operation. Sociodemographics, comorbidities, indications for surgery, graft
      location, and morbidity, mortality, patency, and limb salvage rates were obtained
      via vascular registry. RESULTS: Of 318 patients who underwent revascularization
      over a 1-year period, 276 patients were asked to complete the questionnaires. Of
      the 156 patients who completed both questionnaires, mean age was 66 years, 67%
      were men, 84% had diabetes mellitus, and 83% had various heart-related
      conditions. Mean length of stay was 15.3 days. Distal graft sites were popliteal
      (29%), tibial/peroneal (40%), and pedal/plantar (31%). The operative morbidity
      rate was 21%, the cumulative primary graft patency rate was 93%, the cumulative
      secondary graft patency rate was 95%, and the limb salvage rate was 97% at 6
      months. At follow-up, improved functioning of instrumental activities of daily
      living, mental well-being, and vitality were reported. Symptoms of calf cramping
      and toe or foot pain when walking and at rest were also improved. Sores or ulcers
      improved, but leg swelling did not. The only independent predictor of improved
      function and well-being was the patients' perception of their status at baseline:
      those patients who functioned better before operation reported improved function
      and well-being at 6 months. Only 45% of patients reported feeling "back to
      normal" at 6 months. CONCLUSION: Reported health status at baseline was a
      predictor of improved function, mental well-being, and resolution of symptoms
      after infrainguinal revascularization. Expected return to "normal" may take
      longer than 6 months.

PMID- 7823361
TI  - Carotid artery trauma: a review of contemporary trauma center experiences.
AB  - PURPOSE: Many issues surrounding the management and outcome of carotid artery
      injuries remain controversial. The purpose of this study was to review a large
      contemporary experience with such injuries in the setting of designated trauma
      centers. METHODS: A statewide computerized trauma registry was used to identify
      all patients with injuries to the common or internal carotid arteries from
      October 1987 to June 1993. The records of 82 such patients were retrieved and
      analyzed. RESULTS: Overall mortality and stroke rates were 17% and 28%,
      respectively. Patients presenting with coma or shock had a particularly bad
      prognosis (50% and 41% mortality, respectively). Internal carotid injuries
      resulted in mortality and stroke rates of 21% and 41%, respectively, compared
      with 11% each for common carotid injuries. Patients with blunt injuries had a
      much higher stroke rate (56% vs 15%) but had lower mortality (7% vs 22%) than did
      patients with penetrating injuries. Airway compromise and associated injuries did
      not affect prognosis. Operative repair and percutaneous balloon occlusion had the
      best survival and functional outcomes. CONCLUSIONS: Operative repair offers the
      best chances for recovery in all categories of patients regardless of injury
      mechanism. Ligation is useful only as a last-resort lifesaving effort. Shock and
      neurologic impairment are poor prognostic factors but should not negate repair.

PMID- 7823362
TI  - Arterial injuries in the thoracic outlet syndrome.
AB  - PURPOSE: This article reviews experience with arterial injury caused by thoracic
      outlet syndrome. Special emphasis is placed on the influence of athletic or work
      activities on the axillary-subclavian artery system and the mechanism by which
      the humeral head compresses the axillary artery and the circumflex humeral
      arterial branches. METHODS: Retrospective review identified 34 patients (age
      range 13 to 67 years) treated for upper extremity symptoms or ischemic
      complications of thoracic outlet syndrome from 1983 to 1993. Evaluation included
      assessment of occupational and recreational activities plus duplex
      ultrasonography and contrast arteriography with positional maneuvers. RESULTS:
      Twenty-two patients (27 arms) had subclavian artery injury, which was most
      commonly caused by compression by a bony abnormality (cervical rib, 16; anomalous
      first rib, two; cervical rib and anomalous first rib, two). Fourteen of the 27
      arms had distal embolization. All 27 had surgical decompression of the subclavian
      artery; 15 required concomitant arterial reconstruction. Twelve additional
      patients (nine athletes) had axillary artery involvement, all from arterial
      compression by the head of the humerus during abduction maneuvers; all had
      concomitant compression of the posterior circumflex humeral artery. Axillary
      arterial injury included thrombosis (one), aneurysm (two), and symptomatic
      extrinsic compression only (nine). Five patients with axillary artery involvement
      were treated without a surgical procedure; of the remainder, three underwent
      decompression procedures only, and four had direct arterial repair. In both
      groups all subclavian and axillary artery reconstructions were patent at last
      follow-up examination (mean 31 months). CONCLUSION: Most patients with thoracic
      outlet syndrome who have arterial involvement have a bony anomaly causing
      subclavian artery compression. This study demonstrates that humeral head
      compression of the axillary artery and its circumflex branches is a surprisingly
      common pathologic mechanism. Awareness of this condition affords a better
      therapeutic approach to arterial injuries caused by thoracic outlet syndrome.

PMID- 7823363
TI  - Outcome assessment in vascular surgery--results mean everything.

PMID- 7823364
TI  - Clinical evaluation of recombinant human platelet-derived growth factor for the
      treatment of lower extremity diabetic ulcers. Diabetic Ulcer Study Group.
AB  - PURPOSE: The purpose of this study was to investigate the efficacy and safety of
      recombinant human platelet-derived growth factor (rhPDGF-BB) in a double-blind,
      placebo-controlled, multicenter study of patients with chronic diabetic ulcers.
      METHODS: Patients with chronic, full-thickness, lower-extremity diabetic
      neurotrophic ulcers of at least 8 weeks' duration, free of necrotic and infected
      tissue after debridement, and with transcutaneous oxygen tensions of 30 mm Hg or
      greater were studied. A total of 118 patients were randomized to receive either
      topical rhPDGF-BB (2.2 micrograms/cm2 of ulcer area) or placebo until the ulcer
      was completely resurfaced or for a maximum of 20 weeks, whichever occurred first.
      RESULTS: Twenty-nine (48%) of 61 patients randomized to the rhPDGF-BB group
      achieved complete wound healing during the study compared with only 14 (25%) of
      57 patients randomized to the placebo group (p = 0.01). The median reduction in
      wound area in the group given rhPDGF-BB was 98.8% compared with 82.1% in the
      group given placebo (p = 0.09). There were no significant differences in the
      incidence or severity of adverse events between the rhPDGF-BB and placebo groups.
      CONCLUSIONS: Once-daily topical application of rhPDGF-BB is safe and effective in
      stimulating the healing of chronic, full-thickness, lower-extremity diabetic
      neurotrophic ulcers.

PMID- 7823365
TI  - Assessment of carotid artery stenosis by ultrasonography, conventional
      angiography, and magnetic resonance angiography: correlation with ex vivo
      measurement of plaque stenosis.
AB  - PURPOSE: Several studies have investigated the correlation between Doppler
      ultrasonography (DUS), angiography (CA), and magnetic resonance angiography (MRA)
      in the evaluation of stenosis of the carotid bifurcation. However, these studies
      suffer from the lack of a true control-the lesion itself-and therefore
      conclusions about the diagnostic accuracy of each method remain relative. To
      determine the absolute accuracy of these modalities, we have prospectively
      studied lesion size with DUS, MRA, and CA in 28 patients undergoing 31 elective
      carotid endarterectomies and compared the percent of carotid stenosis determined
      by each technique to the carotid atheroma resected en bloc. METHODS: All patients
      were evaluated by each modality within 1 month before the thromboendarterectomy.
      With DUS, stenosis size was determined by standard flow criteria. For angiography
      and MRA, stenosis was defined as residual lumenal diameter/estimated normal
      arterial diameter (European Carotid Surgery Trial criteria). At surgery the
      carotid atheroma was removed en bloc in all patients. Patients in whom the lesion
      could not be removed successfully without damage were excluded from the study.
      Stenosis of the atheroma was determined ex vivo with high-resolution (0.03 mm3)
      magnetic resonance and confirmed by acrylic injection of the specimen under
      pressure and measurement of the atheroma wall and lumen. RESULTS: The
      measurements of the ex vivo stenosis by high-resolution magnetic resonance
      imaging correlated closely with the size of stenosis determined by the acrylic
      specimen casts (r = 0.92). By ex vivo measurement, the lesions were placed in the
      following size categories: 40% to 59% stenosis (n = 2), 60% to 79% stenosis (n =
      6), 80% to 89% stenosis (n = 7), and 90% to 99% stenosis (n = 16). CONCLUSIONS:
      In general, the correlation of measurements of ex vivo stenosis with all
      modalities was good in these severely diseased arteries, although it was better
      for DUS (r = 0.80; p < 0.001) and MRA (r = 0.76; p < 0.001) than for CA (r =
      0.56; p < 0.05).

PMID- 7823366
TI  - Is transcranial Doppler a worthwhile addition to screening tests for
      cerebrovascular disease?
AB  - PURPOSE: Carotid duplex imaging has become the standard diagnostic evaluation for
      patients with suspected cerebrovascular disease. Transcranial Doppler
      ultrasonography expands the noninvasive diagnostic capabilities to the
      intracranial circulation. The purpose of this study was to evaluate the results
      of routine transcranial Doppler studies on patients referred for noninvasive
      cerebrovascular evaluation. METHODS: A total of 670 patients had routine
      transcranial Doppler examinations as part of their noninvasive cerebrovascular
      evaluation. Patients were categorized clinically and according to their severity
      of extracranial internal carotid artery stenosis (< 50%, 50% to 79%, 80% to 99%,
      occlusion). Transcranial Doppler examinations were classified as normal or
      abnormal (intracranial stenosis, collateral pathway, > 30% velocity difference
      normal or abnormal (intracranial stenosis, collateral pathway, > 30% velocity
      difference between sides, flow reversal, and velocities +/- SD from normal).
      RESULTS: Forty-eight percent of the patients were women, and 52% were men. The
      average age was 65.5 years. Fifty-four percent of the patients were white, 42%
      were black, 3% were Hispanic, and 1% were other. Forty-eight percent presented
      with hemispheric symptoms, 34% had no symptoms, and 18% had nonhemispheric
      symptoms. Forty-five percent (304 of 670) had an interpretable transcranial
      Doppler examination. The ability to insonate the basal cerebral arteries through
      the temporal bone was significantly reduced in women (p < 0.0001), black patients
      (p < 0.0001), and older patients (p < 0.0001). The results of forty-four percent
      of interpretable examinations were normal, 19% demonstrated side-to-side velocity
      differences, 13% showed collateral pathways, 11% showed velocities +/- 2 SD, 10%
      showed an intracranial stenosis, and 4% showed reversed flow pattern. Although
      56% of the patients had notable findings, no patient had their diagnostic or
      therapeutic plan altered by the transcranial Doppler results. CONCLUSION: Less
      than 50% of the patients referred for first-time cerebrovascular examination had
      access for an interpretable transcranial Doppler examination. Though the number
      of positive findings is reasonably high, no material impact on diagnostic or
      treatment plans was seen in the patients in this series. These results indicate
      that selection criteria for examination of the intracranial arteries should be
      refined and that transcranial Doppler scanning should not be incorporated as part
      of the "routine" noninvasive cerebrovascular examination.

PMID- 7823367
TI  - Does routine use of aortic ultrasonography decrease the stroke rate in coronary
      artery bypass surgery?
AB  - PURPOSE: The purpose of this study is to determine whether the routine use of
      intraoperative surface aortic ultrasonography decreases the stroke rate in
      coronary artery bypass graft surgery (CABG). METHODS: One hundred ninety-five
      consecutive patients undergoing CABG between July 1, 1992, and June 30, 1993
      (study group), were evaluated by intraoperative surface aortic ultrasonography.
      Based on information obtained, changes in the operative technique were made in an
      effort to decrease the incidence of embolic stroke from unsuspected
      atherosclerotic disease of the ascending aorta. The outcome of these patients was
      compared with that of 164 consecutive patients who underwent CABG between July 1,
      1991, and June 30, 1992 (control group), in whom the ascending aorta was assessed
      by inspection and palpation only. RESULTS: Significant disease was detected in
      three (2.0%) of 164 patients in the control group. Modifications in their
      operative technique consisted of hypothermic fibrillatory arrest with no cross
      clamping of the aorta and left ventricular venting in two patients and single
      cross-clamping in one patient. There were five strokes overall in this group
      (3.0%), and six patients died (3.6%), one in whom the stroke contributed directly
      to the cause of death. In the study group the ultrasonic findings were normal to
      mild in 168 patients, moderate in 20 patients, and severe in seven patients.
      These results led to a modification of the technique in 19 patients, (10%):
      hypothermic fibrillatory arrest with no cross-clamping of the aorta and left
      ventricular venting in 14 patients, modification in the aortic cannulation site
      or single cross-clamping in three patients, and modification in placement of
      proximal anastomoses or all arterial grafts in two patients. No strokes occurred
      in this group (p < 0.02, Fisher's exact test). Five patients died, for an
      operative mortality rate of 2.6%. CONCLUSION: These data indicate that
      intraoperative ultrasonography of the ascending aorta with simple modifications
      in operative technique reduces the stroke rate in CABG.

PMID- 7823368
TI  - A piece of my mind. Why medicine.

PMID- 7823369
TI  - Medicine's position is both pivotal and precarious in assisted-suicide debate.

PMID- 7823371
TI  - Interactive medical video communication appears to be ahead, but many early
      efforts left behind.

PMID- 7823370
TI  - Donor pool may rise as screening blood test falls.

PMID- 7823372
TI  - From the Centers for Disease Control and Prevention. Cigarette smoking among
      adults--United States, 1993.

PMID- 7823373
TI  - From the Centers for Disease Control and Prevention. Differences in maternal
      mortality among black and white women--United States, 1990.

PMID- 7823374
TI  - From the Centers for Disease Control and Prevention. Abortion surveillance:
      preliminary data--United States, 1992.

PMID- 7823375
TI  - From the Centers for Disease Control and Prevention. Injuries among construction
      workers during the raising of wood-framed walls--Colorado and California.

PMID- 7823376
TI  - The apolipoprotein E E4 allele and sex-specific risk of Alzheimer's disease.

PMID- 7823377
TI  - Apolipoprotein E E4 allele and risk of dementia.

PMID- 7823378
TI  - Helicobacter pylori and ulcer in patients taking NSAIDs.

PMID- 7823379
TI  - Spironolactone and hepatic toxicity.

PMID- 7823380
TI  - Maternal-fetal transmission of HIV-1.

PMID- 7823381
TI  - Hepatitis E in patients with chronic autoimmune liver disease.

PMID- 7823382
TI  - Irradiation and contaminated meat.

PMID- 7823383
TI  - Serogroup C meningococcal outbreaks in the United States. An emerging threat.
AB  - OBJECTIVE: Multiple outbreaks of serogroup C Neisseria meningitidis have recently
      been reported from diverse areas of the United States. To better define the
      characteristics of this increasingly important problem, we reviewed data on all
      known serogroup C outbreaks in the United States from January 1980 through June
      1993. DATA SOURCES: MEDLINE searches, Centers for Disease Control and Prevention
      records, state health department officials, infectious disease experts, and the
      meningococcal vaccine manufacturer. DEFINITION OF AN OUTBREAK: Three or more
      cases of serogroup C meningococcal disease within a 3-month period, either among
      members of a community or persons attending a single school or other institution,
      for which those cases represented an attack rate of at least five per 100,000
      population. RESULTS: Twenty-one outbreaks of serogroup C meningococcal disease
      were identified; eight occurred since 1991. In 1992 and the first half of 1993,
      approximately 180,000 doses of vaccine were administered for outbreak control,
      compared with approximately 34,000 doses from 1980 to 1991. Approximately 50% of
      community-outbreak cases were between the ages of 5 and 24 years, compared with
      only 19% of sporadic serogroup C cases (P < .001). Subtyping of patient isolates
      indicates that outbreaks are clonal; however, at least five distinct but closely
      related strains have caused recent outbreaks. CONCLUSIONS: Serogroup C outbreaks
      are occurring more frequently in the United States. The effectiveness of
      preventive measures depends on early recognition; therefore, physicians should
      promptly report all cases of suspected meningococcal disease, and the causative
      serogroup should be established for every case.

PMID- 7823384
TI  - The changing epidemiology of invasive meningococcal disease in Canada, 1985
      through 1992. Emergence of a virulent clone of Neisseria meningitidis.
AB  - OBJECTIVE: To describe the occurrence of invasive meningococcal disease (IMD) in
      Canada with respect to demographic variables and characteristics of the isolated
      strains of Neisseria meningitidis. DESIGN: National surveillance case series.
      SETTING: Canada, 1985 through 1992. OUTCOME MEASURES: Morbidity and mortality.
      MAIN RESULTS: The incidence of IMD averaged 1.38 per 100,000 person-years, with
      considerable regional variation. In 1988, serogroup C organisms became more
      common, with one strain of the electrophoretic type 37 (ET-37) complex of N
      meningitidis, termed ET-15, the predominant group C strain identified. With the
      increase in group C disease, a greater proportion of cases were older than 5
      years. By 1991, ET-15 was the most common strain identified in most parts of the
      country. Electrophoretic type 15 had a case fatality of 17.8% vs 8.1% for all
      other IMD (P < .001). Among cases 20 years and older the case fatality for ET-15
      was 22.4%. CONCLUSIONS: The group C, ET-15 strain of N meningitidis, first
      identified in Canada, was more virulent than other prevalent strains during this
      period. Active surveillance, rapid identification, and typing of N meningitidis
      will assist public health decision making in the control of emerging strains.

PMID- 7823385
TI  - Progress in the development of trauma systems in the United States. Results of a
      national survey.
AB  - OBJECTIVE: To examine the status of trauma system development and key structural
      and operational characteristics of these systems. DESIGN AND SETTING: National
      survey of trauma systems with enabling state statute, regulation, or executive
      orders and for which designated trauma centers were present. PARTICIPANTS: Trauma
      system administrators and directors of 37 state and regional organizations that
      had legal authority to administer trauma systems, which represented a response
      rate of 90.2%. MAIN OUTCOME MEASURES: Trauma system components that had been
      implemented or were under development. RESULTS: From 1988 to 1993, the number of
      states meeting one set of criteria for a complete trauma system criteria
      increased from two to five. The most common deficiency in establishing trauma
      systems was failure to limit the number of designated trauma centers based on
      community need. Although most existing trauma systems have developed formal
      processes for designating trauma centers, prehospital triage protocols to allow
      hospital bypass, and centralized trauma registries, several systems lack
      standardized policies for interhospital transfer and systemwide evaluation.
      CONCLUSION: State and regional organizations have accomplished a great deal but
      still have substantial work ahead in developing comprehensive trauma systems.
      Research is needed to better understand the relationship between trauma volume
      and outcomes of care as well as the impact of trauma system structure and
      operational characteristics on care delivery. Improved measures of patient
      outcome are also needed so that effective system evaluation can take place.

PMID- 7823386
TI  - Physical activity and public health. A recommendation from the Centers for
      Disease Control and Prevention and the American College of Sports Medicine.
AB  - OBJECTIVE: To encourage increased participation in physical activity among
      Americans of all ages by issuing a public health recommendation on the types and
      amounts of physical activity needed for health promotion and disease prevention.
      PARTICIPANTS: A planning committee of five scientists was established by the
      Centers for Disease Control and Prevention and the American College of Sports
      Medicine to organize a workshop. This committee selected 15 other workshop
      discussants on the basis of their research expertise in issues related to the
      health implications of physical activity. Several relevant professional or
      scientific organizations and federal agencies also were represented. EVIDENCE:
      The panel of experts reviewed the pertinent physiological, epidemiologic, and
      clinical evidence, including primary research articles and recent review
      articles. CONSENSUS PROCESS: Major issues related to physical activity and health
      were outlined, and selected members of the expert panel drafted sections of the
      paper from this outline. A draft manuscript was prepared by the planning
      committee and circulated to the full panel in advance of the 2-day workshop.
      During the workshop, each section of the manuscript was reviewed by the expert
      panel. Primary attention was given to achieving group consensus concerning the
      recommended types and amounts of physical activity. A concise "public health
      message" was developed to express the recommendations of the panel. During the
      ensuing months, the consensus statement was further reviewed and revised and was
      formally endorsed by both the Centers for Disease Control and Prevention and the
      American College of Sports Medicine. CONCLUSION: Every US adult should accumulate
      30 minutes or more of moderate-intensity physical activity on most, preferably
      all, days of the week.

PMID- 7823387
TI  - Empirical evidence of bias. Dimensions of methodological quality associated with
      estimates of treatment effects in controlled trials.
AB  - OBJECTIVE: To determine if inadequate approaches to randomized controlled trial
      design and execution are associated with evidence of bias in estimating treatment
      effects. DESIGN: An observational study in which we assessed the methodological
      quality of 250 controlled trials from 33 meta-analyses and then analyzed, using
      multiple logistic regression models, the associations between those assessments
      and estimated treatment effects. DATA SOURCES: Meta-analyses from the Cochrane
      Pregnancy and Childbirth Database. MAIN OUTCOME MEASURES: The associations
      between estimates of treatment effects and inadequate allocation concealment,
      exclusions after randomization, and lack of double-blinding. RESULTS: Compared
      with trials in which authors reported adequately concealed treatment allocation,
      trials in which concealment was either inadequate or unclear (did not report or
      incompletely reported a concealment approach) yielded larger estimates of
      treatment effects (P < .001). Odds ratios were exaggerated by 41% for
      inadequately concealed trials and by 30% for unclearly concealed trials (adjusted
      for other aspects of quality). Trials in which participants had been excluded
      after randomization did not yield larger estimates of effects, but that lack of
      association may be due to incomplete reporting. Trials that were not double-blind
      also yielded larger estimates of effects (P = .01), with odds ratios being
      exaggerated by 17%. CONCLUSIONS: This study provides empirical evidence that
      inadequate methodological approaches in controlled trials, particularly those
      representing poor allocation concealment, are associated with bias. Readers of
      trial reports should be wary of these pitfalls, and investigators must improve
      their design, execution, and reporting of trials.

PMID- 7823388
TI  - Effect of corticosteroids for fetal maturation on perinatal outcomes. NIH
      Consensus Development Panel on the Effect of Corticosteroids for Fetal Maturation
      on Perinatal Outcomes.
AB  - OBJECTIVE: To develop a consensus on the use of antenatal corticosteroids for
      fetal maturation in preterm infants. PARTICIPANTS: A nonfederal, nonadvocate, 16
      member consensus panel including representatives from neonatology, obstetrics,
      family medicine, behavioral medicine, psychology, biostatistics, and the public;
      19 experts in neonatology, obstetrics, and pharmacology presented data to the
      consensus panel and a conference audience of approximately 500. EVIDENCE: An
      extensive bibliography of references was produced for the consensus panel and the
      conference audience using a variety of on-line databases including MEDLINE. The
      consensus panel met several times prior to the conference to review the
      literature. It also commissioned an updated meta-analysis, a neonatal registry
      review, and an economic analysis that were presented at the conference. The
      experts prepared abstracts for distribution at the conference, presented data,
      and answered questions from the panel and audience. The panel evaluated the
      strength of the scientific evidence using the grading system developed by the
      Canadian Task Force on the Periodic Health Examination and adapted by the US
      Preventive Services Task Force. CONSENSUS: The consensus panel, answering
      predefined consensus questions, developed their conclusions based on the
      scientific evidence presented in open forum and the scientific literature.
      CONSENSUS STATEMENT: The consensus panel composed a draft statement that was read
      in its entirety at the conference for comment. The panel released a revised
      statement at the end of the conference and finalized the revisions a few weeks
      after the conference. CONCLUSIONS: Antenatal corticosteroid therapy is indicated
      for women at risk of premature delivery with few exceptions and will result in a
      substantial decrease in neonatal morbidity and mortality, as well as substantial
      savings in health care costs. The use of antenatal corticosteroids for fetal
      maturation is a rare example of a technology that yields substantial cost savings
      in addition to improving health.

PMID- 7823390
TI  - Trauma systems. A model for regionalized care.

PMID- 7823389
TI  - The worldwide prevention of meningococcal infection. Still an elusive goal.

PMID- 7823391
TI  - The Arbor Free Clinic at Stanford: a multidisciplinary effort.

PMID- 7823392
TI  - The Hahnemann Homeless Clinics Project: taking health care to the streets and
      shelters.

PMID- 7823393
TI  - Eight steps for starting a student-run clinic.

PMID- 7823394
TI  - [The monitoring of cytomegalovirus antigenemia and arterial oxygen saturation for
      the early detection of cytomegalovirus pneumonia].
AB  - Eighteen patients underwent allogeneic bone marrow transplantation (allo. BMT)
      during the period May, 1991 to December, 1992 in the Center for Adult Diseases,
      Osaka. They were monitored for cytomegalovirus (CMV) antigenemia and arterial
      oxygen saturation (SaO2). More than 10 antigen-positive cells per 50,000
      polymorphonuclear leukocytes were detected in five of 18 patients. Three of these
      5 patients developed CMV pneumonia several weeks after the first detection of
      more than 10 positive cells. Six of 18 patients developed interstitial pneumonia
      (IP) (3 CMV pneumonia and 3 idiopathic IP). SaO2 decreased less than 95% several
      days before the development of IP in 3 of these 6 patients (2 of CMV pneumonia
      and 1 of idiopathic IP). CMV antigenemia assay and SaO2 assay were thus both
      considered to be useful for the early detection or prediction of development of
      CMV pneumonia.

PMID- 7823395
TI  - [Anemia and neutropenia in elderly patients caused by copper deficiency for long
      term enteral nutrition].
AB  - Anemia and neutropenia caused by copper deficiency is a well-known consequence of
      long term total parenteral nutrition in the literature. We present 6 bed-ridden
      elderly patients who developed anemia and neutropenia after receiving enteral
      nutrition for a long time (mean: 3.3 years) In all 6 patients, serum copper and
      ceruloplasmin level were very low, and the mean of their hematological data were
      as follows: WBC 2,200/microliters, neutrophil 554/microliters, hemoglobin 8.1
      g/dl, platelet 260 x 10(3)/microliters, respectively. The bone marrow examination
      showed cytoplasmic vacuolization of both myeloid and erythroid precursors, and
      maturation arrest of granulopoiesis. Then, copper sulfate was administrated by
      enteral tube to 6 patients, and the improvement of anemia and neutropenia was
      observed within a month. A 82-year-old woman who received enteral nutrition for
      3.5 years with sever anemia (Hb 3.7 g/dl) and neutropenia (neutrophil
      350/microliters), showed a marked improvement in hematological data (Hb 8.0 g/dl,
      neutrophil 4, 092/microliters, respectively) after two months by administering
      the copper supplementation. The exact cause of the anemia and neutropenia in
      copper deficiency is unclear, but it is suggested that the decreased activity of
      enzyme containing copper may be related. Hematological abnormalities due to
      copper deficiency should be cared during long term enteral nutrition with long
      termed bed-ridden elderly patients.

PMID- 7823396
TI  - [Immunocytochemistry in the diagnosis of acute myeloid leukemia (M0)].
AB  - We examined leukemic blasts from 5 cases of AML-M0 diagnosed according to The
      French-American-British (FAB) classification for expression of immunological
      markers as well as myeloperoxidase (MPO) using flow cytometry (FCM) and
      immunocytochemistry (ICC). In one patient, the myeloid antigens, CD13 and CD33,
      were negative on FCM, but apparently positive in the cytoplasm by ICC, leading to
      a diagnosis of AML-M0. We examined MPO with anti-MPO monoclonal antibody in four
      patients by ICC, and could detect 3% or more MPO positive rates in all cases.
      These findings indicate that immunological studies for MPO and myeloid markers
      using ICC are very useful for the diagnosis of AML-M0. Two of 5 patients achieved
      CR, but they relapsed soon or after one year, respectively. The treatment
      outcomes suggest that the AML-M0 is an AML subtype with poor prognosis.

PMID- 7823397
TI  - [IgD myeloma with skin tumor].
AB  - A 66-year-old man was treated for IgD (lambda) multiple myeloma with 2mg/day
      melphalan and 20mg/day prednisolone. Subsequently, he developed pneumonia for
      which he received antibiotics, an antifungal agent and granulocyte colony
      stimulating factor (G-CSF) twice. Myeloma cells appeared in the peripheral blood
      10 days after the second G-CSF course. In addition, skin tumors developed on his
      extremities and chest 14 days after the second use of G-CSF. The skin tumors
      consisted of immunohistochemically IgD (lambda)-positive myeloma cells. The skin
      tumors may have been formed from the bone marrow by metastasis, a very rare
      occurrence in multiple myeloma. Before the development of the tumors we
      administered G-CSF, which may also have been related to the formation of the skin
      tumors.

PMID- 7823398
TI  - [Multiple myeloma preceding myelodysplastic syndrome with eosinophilia and der
      (1;7)].
AB  - Multiple myeloma (IgG kappa + IgA kappa type, clinical stage IA) was diagnosed in
      a 82-year-old woman in January 1986. Chemotherapy (melphalan, prednisolone,
      vindesine, cyclophosphamide), caused prolonged myelosuppression. Therefore she
      was given other treatment. In October 1992, her peripheral blood examination
      demonstrated 2% blastic cells and 12% eosinophils. Bone marrow aspiration showed
      dysplastic features of trilineage blood cells with 4.8% myeloblasts. The
      karyotype of bone marrow cells from this patients was 47, XX, +der(1)t(1;7)
      (p11;p11), -7, +8. A diagnosis of therapy-related myelodysplastic syndrome
      (refractory anemia) was established. Eleven months after diagnosis of
      myelodysplastic syndrome, she is alive without leukemic transformation.

PMID- 7823399
TI  - [Multicentric Castleman's disease accompanied with both lymphoid interstitial
      pneumonia and interstitial nephritis].
AB  - A 60-year old man admitted in November, 1991 because of hyperproteinemia. He had
      shown a gradual increase in serum levels of gamma-globulin since 1981, and
      idiopathic plasmacytic lymphadenopathy with hyperimmunoglobulinemia was diagnosed
      in 1989 when he was admitted to another hospital because of persistent swelling
      of bilateral inguinal lymph nodes since 1986. Multiple swelling of lymph nodes
      was observed in the right supraclavicle fossa, the left axillary and bilateral
      inguinal region, and diffuse reticulo-nodular shadows were observed on his chest
      roentogenogram. Other laboratory findings were as follows; erythrocyte
      sedimentation rate 143 mm/hr, CRP 3+, Hb 9.4 g/dl, TP 13.7 g/dl with 69.4% of
      beta-gamma bridge, BUN 21.1 mg/dl, creatinine 1.6 mg/dl, PaO2 77.6 mmHg, plasma
      cell count in bone marrow 6.4% and positive tests for autoantibodies such as
      rheumatoid factor, anti-DNA antibody, anti-smooth muscle antibody, and direct
      Coombs test. Serum interleukin-6 (IL-6) level increased to 259 pg/ml and IL-1
      beta was 39.1 pg/ml. Specimens of both transbronchial lung biopsy and fine-needle
      kidney biopsy revealed a marked infiltration of lymphocytes and plasma cells into
      interstitial regions of lung and kidney. We reported here a case of multicentric
      Castleman's disease (MCD) who also demonstrated lymphoid interstitial pneumonia
      and interstitial nephritis. The present study suggests that some cytokines
      including IL-6 and IL-1 beta may be closely related to the pathophysiology of
      MCD.

PMID- 7823400
TI  - [A case of chronic neutrophilic leukemia accompanied with severe bone marrow
      fibrosis which was effectively treated by hydroxyurea].
AB  - A 57-year-old man was admitted to hospital because of leukocytosis. He showed
      mild splenomegaly and, laboratory studies revealed elevated mature neutrophil
      count without morphological abnormality, mild anemia and elevated neutrophil
      alkaline phosphatase score. The serum granulocyte colony stimulating factor
      concentration was below 30 pg/ml. Bone marrow was a dry tap, and biopsy specimen
      revealed severe fibrosis. The peripheral blood karyotype was 46, XY with no
      rearrangement of bcr-abl. The patient was diagnosed as having chronic
      neutrophilic leukemia (CNL) with bone marrow fibrosis. He was successfully
      treated with hydroxyurea (HU) 1000 mg/day. The peripheral blood leukocyte was
      decreased to the normal level and, the bone marrow biopsy specimen changed mild
      fibrosis. During the follow up period of 11 months, the neutrophil count was well
      controlled without any side effect. This is a rare case of CNL accompanied with
      bone marrow fibrosis which was effectively treated by the administration of HU.

PMID- 7823401
TI  - [Mortality from major causes of death and its risk factors in the elderly--26
      year follow-up study in Hisayama].
AB  - The authors studied mortality from major causes of death and risk factors in the
      elderly in a long-term prospective survey conducted in a Japanese suburban
      community, Hisayama. In the baseline survey in 1961, we scrutinized 1658
      residents of the town aged 40 years or older accounting for 92% of the total
      population in this age range. Of those, 591 residents (245 men and 346 women)
      aged 60 years or older, who were free from major cardiovascular disease, were
      selected for the present study. They were followed-up for 26 years from 1961 to
      1987. The average age was 67 years for men and 70 years for women, being
      significantly higher for women than for men. During the follow-up period, 529
      subjects (89.5%) died, and 448 were autopsied (autopsy rate 84.7%). The all-cause
      mortality (per 1,000 person-years) after adjustment for age was 89.9 for men and
      56.7 for women, the former being significantly higher than the latter (p < 0.01).
      The age-adjusted mortality from cerebrovascular disease was estimated to be 21.4
      for men and 9.9 for women, i.e. 8.9 and 8.8 from heart disease, and 19.9 and 10.6
      from neoplasm, and 18.1 and 12.2 from-pneumonia, respectively. There was
      significant sex difference in mortality from cerebrovascular disease, neoplasm
      and pneumonia (p < 0.01) but not from heart disease (p > 0.1). Multiple Cox's
      proportional hazards regression analysis showed systolic blood pressure and male
      sex to be significant risk factors for death by cerebrovascular disease. Systolic
      blood pressure was also a predictor for death by heart disease.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7823402
TI  - [The role of platelet in the etiology of Binswanger's disease].
AB  - White matter changes, which are noted in Binswanger's disease and which may be
      due to ischemia, have previously been explained mainly on the basis of the
      hemodynamic mechanism. To elucidate the etiopathophysiology of Binswanger's
      disease from the hemorheology viewpoint, platelet activation in the cerebral
      circulation was studied in 30 patients with Binswanger's disease, who satisfied
      the diagnostic criteria of Binswanger's disease proposed by Bennett et al. Plasma
      beta-thromboglobulin concentration gradients (delta BTG) between the jugular vein
      and the antecubital vein, as indicators of platelet activation in the cerebral
      circulation, were determined in these patients (Binswanger's disease group)
      compared with those of different stroke subtypes groups (lacunar,
      atherothrombotic, cardioembolic) in the chronic phase and 25 patients with
      various diseases other than stroke (non-stroke group). Among these groups, the
      elevation of delta BTG levels in the Binswanger's disease group (4.55 +/- 6.95)
      were so frequent and prominent that differences were significant, especially in
      comparison to those of the cardioembolic group, and the non-stroke group. The
      enhanced platelet activation in the cerebral circulation observed in Binswanger's
      disease indicated not only the widespread development of underlying vascular
      lesions, but also accelerated release reaction of vasoactive substances from
      platelets into the blood stream, which could biochemically injure the vascular
      wall and neurons downstream, resulting in Binswanger's disease.

PMID- 7823403
TI  - [Neuroimaging in the diagnosis of Alzheimer's disease].
AB  - We sought to identify a marker for Alzheimer's disease (AD) for antemortem
      diagnosis. To determine whether the detection of reduced blood flow in the
      parietotemporal cortex, shown by single photon emission CT (SPECT), and of medial
      temporal lobe atrophy, shown by magnetic resonance imaging (MRI), would be useful
      in diagnosis, we studied 38 patients with AD diagnosed by the NINCDS-ADRDA
      criteria and 26 healthy elderly controls. Parietotemporal hypoperfusion was
      qualitatively assessed by physicians who were unaware of the clinical diagnosis,
      and the severity of medial temporal lobe atrophy was quantitated by planimetric
      and linear measurements. Although an accurate diagnosis of AD was made in 80% or
      more of the patients by SPECT or MRI studies alone, the combination of SPECT and
      MRI gave a higher diagnostic accuracy, with a sensitivity of 95% and a
      specificity of 92%. Since regional functional or structural changes were detected
      in 92% of early or mild patients, including possible AD, the combination of SPECT
      and MRI studies were useful in the early diagnosis of AD. Findings suggest that a
      functional abnormality in the parietotemporal lobe and an atrophic change in the
      medial temporal lobe are characteristic of AD, and that SPECT and MIR regional
      changes may be useful as antemortem diagnostic markers.

PMID- 7823404
TI  - [A questionnaire survey on urinary incontinence and urinary disturbances in the
      institutionalized elderly with senile dementia].
AB  - We carried out a questionnaire survey concerning urinary disturbances, among
      nursing home patients. The answers were obtained from 1,038 elderly including 355
      males and 683 females. Ages, spanned 50-99, with an average age of 79.1. Of the
      1,038 respondents which we obtained through our survey for management of
      urination, 35.8% of the total said that they are able to urinate without
      incontinence. Those able to urinate with incontinence accounted for 23.6% of the
      total. However, 40% of all patients required an adult diaper throughout the day
      to control their urinary functions. Patients suffering from neurological
      disorders accounted for 70% of respondents, and a correlation was seen between
      the extent of dementia and ADL, and excretory control. Urinary functioning in
      both men and women was found to grow increasingly difficult with age, and medical
      problems involving urinary difficulty appear to increase with the advance of the
      aging process. The representative groups for this survey were limited to elderly
      people in nursing homes, many of whom suffer from neurological disorders such as
      cerebral infarction. It was found that both male and female patients experience a
      variety of urinary disturbances.

PMID- 7823405
TI  - [The effect of age and disease on the MR imaging T2 low signal intensity area in
      the cerebral cortex].
AB  - We retrospectively studied magnetic resonance (MR) images of the brain in 139
      patients (16 cases of Alzheimer's disease, 8 cases of Parkinson's disease, 53
      cases of multiple cerebral infarct, 33 cases of other central nervous diseases,
      and 29 cases of peripheral neuropathy) between the age of 6 and 85 years old with
      a mean age of 60.6 +/- 18.5 to examine the appearance of T2 low signal intensity
      areas (T2CLIA) in the cerebral cortex. Motor, occipital, sensory or other
      cortices were evaluated with long repetition time/echo time (TR/TE) spin-echo
      sequences and staged into three grades in the motor cortex: none, partial, and
      whole; and two grades in the others: none or present. In general, T2CLIA was not
      seen in any cortex in patients less than 50 years old, then after 50 years old
      T2CLIA increased with age. Over 70 years of age T2CLIA appeared in 50.9% of
      patients in the whole motor cortex, 88.7% in either whole or partial motor
      cortex, 47.2% in the occipital cortex, and 20.8% in the sensory cortex. T2CLIA
      was not observed in other cortices. The incidence of T2CLIA appearance in the
      motor cortex was significantly higher in all central nervous diseases than in
      cases of peripheral neuropathy over 70. T2-CLIA showed a correlation with
      temporal lobe atrophy and white matter lesions in the motor cortex. In the
      sensory cortex, T2CLIA correlated with white matter lesions. These results
      suggest that T2-CLIA may correlate with age or accumulation of nonheme iron in
      the cortex associated with central nervous diseases.

PMID- 7823406
TI  - [Very low-intensity anticoagulant therapy in elderly cardioembolic stroke
      patients with nonvalvular atrial fibrillation].
AB  - Several investigations revealed the significant effect of anticoagulant therapy
      for stroke prevention in patients with atrial fibrillation. However, in the
      elderly population, the optimal therapeutic strategy of secondary prevention of
      cardioembolic stroke is still controversial. We prospectively evaluated the
      efficacy and safety of very low-intensity anticoagulant therapy (target range,
      Thrombotest = 20-30%: INR = 1.47-1.81) for elderly cardioembolic stroke patients
      due to nonvalvular atrial fibrillation. Twenty cardioembolic stroke patients
      (average age 80.0) with nonvalvular atrial fibrillation were included in our
      study. Anticoagulant therapy began 5 of 7 days after the embolic event. The
      incidental rate of ischemic stroke recurrence and bleeding complication were
      evaluated. During mean follow-up of 14.7 month, the annual recurrent rate of
      ischemic stroke was 8.2% (cardioembolic stroke = 4.1%/year, atherothrombotic
      stroke = 0%/year, lacunar stroke = 4.1%/year), whereas one non-fatal
      gastrointestinal bleeding was observed. Our study suggested that even in the
      elderly population, very low-intensity anticoagulant therapy may be effective,
      and safe with respect to prevention of bleeding complications, for secondary
      cardioembolic stroke prevention.

PMID- 7823407
TI  - [An elderly patient with Takayasu's arteritis associated with antiphospholipid
      antibodies].
AB  - We report a patient with Takayasu's arteritis associated with antiphospholipid
      antibodies. An 84-year-old woman gradually developed gait and visual
      disturbances, dementia, myocardial infarction, and gangrene in all four limbs
      during a period of 8 years. Persistent inflammatory signs also continued for at
      least 8 years. Positive reaction for lupus anticoagulant by the diluted Russel
      viper venous time and positive reactions for cardiolipin antibodies were
      confirmed. However, she did not develop SLE. MR angiography revealed multiple and
      extensive occlusive changes in large vessels such as the aorta and its major
      branches. We believe antiphospholipid antibodies may have been related to severe
      occlusive vasculopathy in this patient.

PMID- 7823408
TI  - [Determinants of morale scale of rural and urban elderly diabetics in Japan].

PMID- 7823409
TI  - Electron microscopic study of the distribution and the vertical transmission of
      Rickettsia tsutsugamushi in Leptotrombidium pallidum.
AB  - Leptotrombidium pallidum naturally infected with Rickettsia tsutsugamushi was
      reared and bred in our laboratory for several generations by brother and sister
      mating. The larvae and adults at the 8th and 9th generations were sectioned and
      observed by electron microscopy for analysis for the distribution of rickettsiae
      in the mites. The distribution densities of rickettsiae were markedly different
      among organs in each mite, but rickettsiae were seen in all the organs and
      tissues. Rickettsiae were distributed in the highest density in the salivary
      gland of larvae, and in the salivary gland, excretory bladder, epidermal layer,
      ovary and testis of adult mites. Only a few rickettsiae were recognized in the
      muscle of both larvae and adults. On the other hand, we found, in the infected
      family line used, a significant number of mites in which no rickettsiae were
      found by electron microscopy. The grouping of rickettsia-positive and -negative
      mites according to the parent family revealed that the efficiency of vertical
      transmission of rickettsia was different from one parent family to another. Thus,
      it became clear that a significant number of rickettsia-negative mites are
      produced in an infected family line.

PMID- 7823410
TI  - Specific detection of Aspergillus and Penicillium species from respiratory
      specimens by polymerase chain reaction (PCR).
AB  - A polymerase chain reaction (PCR) method capable of detecting both Aspergillus
      fumigatus infections, pulmonary non-fumigatus Aspergillus species (spp.) and
      Penicillium spp. from clinical specimens was established. The primer pair was
      designed on the basis of the sequence of the 18S-ribosomal RNA gene of A.
      fumigatus and P. notatum. A 385 bp product was successfully amplified by this PCR
      method from all of 12 medically important Aspergillus spp. and Penicillium spp.
      (38 strains), but not from human, calf, Escherichia coli, methicillin-resistant
      Staphylococcus aureus (MRSA), any of 14 medically important yeastlike fungal
      species tested (32 strains) including Candida albicans, several non-albicans
      Candida and Saccharomyces cerevisiae, Cryptococcus neoformans, Mucor spp. or
      Pneumocystis carinii. This specificity was subsequently confirmed by Southern
      hybridization analysis. The established PCR can detect such a small amount as 1
      pg of A. fumigatus DNA by staining the PCR product with ethidium bromide. With
      sputum specimens from clinically diagnosed aspergilloma patients, this PCR
      technique was demonstrated to be a more sensitive diagnostic method for
      Aspergillus infections than conventional culture techniques.

PMID- 7823411
TI  - A simple and efficient method for purification of infectious recombinant
      adenovirus.
AB  - Recently, the adenovirus expression vector attracts much attention for the
      application to gene therapy and the method to purify and concentrate adenovirus
      without loss of infectivity has become very important, especially for animal
      experiments and gene therapy of humans. In this report, we show a simple and
      efficient method for purifying infectious adenovirus. The method consists of
      sequential centrifugation in CsCl step gradients without loss of infectivity and
      can be completed in one day. The method maintained the viral infectivity after 10
      fold concentration and seemed to remove more than 99.9% of carried-over proteins.
      We showed also that the buffers for dialyzing the purified virions influenced the
      stability of infectivity. The buffers of 10 mM HEPES-1 mM EDTA-10% glycerol and
      PBS(-)-10% glycerol resulted in higher stability than did 10 mM HEPES-1 mM MgCl2
      10% glycerol. The method is may be useful in many applications of recombinant
      adenovirus.

PMID- 7823413
TI  - Somatic afferent regulation of plasma immunoreactive glucagon in anesthetized
      rats.
AB  - We examined the neural mechanisms of the effect of noxious and innocuous
      mechanical stimulation of various segmental skin areas on the plasma glucagon
      concentration. Experiments were performed using chloralose- and urethane
      anesthetized rats, ventilated artificially. The cutaneous stimuli of two
      different modalities, noxious and innocuous mechanical stimuli by pinching and
      brushing, were delivered to various segmental areas including the face, forelimb
      for forepaw, abdomen, and hindlimb or hindpaw. Blood samples were collected from
      the femoral artery, and plasma glucagon was measured by radioimmunoassay.
      Cutaneous pinching for 3.5 min of the face, forepaw, abdomen, or hindpaw
      increased the plasma immunoreactive glucagon (IRG), and the increase was larger
      following pinching of the abdmen or hindpaw than pinching of the face or forepaw.
      Brushing for 3.5 min of the face, forelimb, abdomen, or hindlimb did not
      significantly affect the plasma IRG. The increase in plasma IRG following skin
      pinching was abolished when both parasympathetic vagal and sympathetic nerves to
      the pancreas were bilaterally severed. The increase in plasma IRG was not
      abolished after bilateral severance of either the parasympathetic vagal or
      sympathetic nerves alone. These findings indicate that excitation of cutaneous
      nociceptive afferent information from the various spinal segments can regulate
      glucagon secretion from the pancreas as a reflex response, whose efferent limb is
      dually composed of both sympathetic and parasympathetic nerves.

PMID- 7823412
TI  - Phylogenetic comparison between archetypal and disease-associated JC virus
      isolates in Japan.
AB  - We examined the phylogenetical correlation between two types of JC virus (JCV)
      isolates, archetypes derived from the urine of nonimmunocompromised individuals
      and PML-types derived from the brain of patients with progressive multifocal
      leukoencephalopathy (PML) in Japan. A phylogenetic tree was constructed for eight
      JCV isolates, five PML-types obtained in this and previous studies and three
      representative archetypes, from DNA sequence data on the VP1 (major capsid
      protein) gene. The eight isolates were divided into two major groups, named
      subtypes MY and CY after the representative archetypal isolates. Four of five PML
      type isolates belonged to subtype MY, and the other one to subtype CY. Isolates
      belonging to subtype MY were further divided into two groups; one group
      containing archetype MY and three PML-types and the other one containing
      archetype YI and a PML-type. These findings, together with those in our previous
      study that correlated various JCV isolates in the world provide evidence for the
      hypothesis that JCVs associated with PML may have been generated from archetypal
      JCVs persisting in the patients.

PMID- 7823414
TI  - Changes in sleep-wakefulness after kainic acid lesion of the preoptic area in
      rats.
AB  - The role of the preoptic area (POA) neurons in the regulation of sleep
      wakefulness (S-W) has been investigated in this study. The cell-specific
      neurotoxin, kainic acid (KA), was injected (0.8 microgram in 0.2 microliter)
      intracerebrally for lesioning of the POA. S-W was assessed (on the basis of EEG,
      EMG, and EOG recordings) for a day before bilateral lesion of the POA, and for 3
      weeks after the lesion. There was an increase in wakefulness, and a decrease in
      all the stages of sleep after KA lesion of the POA. The reduction in deep slow
      wave sleep (S2) and REM sleep (PS) were more marked than light slow wave sleep
      (S1), and these had not shown any recovery even after 3 weeks of lesion. Two days
      after the lesion, the reduction in sleep was much more marked during the daytime
      than at night. There was an increase in locomotor activity, especially during the
      daytime, though it was only statistically significant on the 6th and the 10th day
      after the lesion. This study shows that the POA neurons are involved in the
      induction and maintenance of sleep. The lesion did not have a long lasting effect
      on the circadian distribution of sleep but the changes in locomotor activity seem
      to persist for a longer period.

PMID- 7823415
TI  - Time course of recovery from pancreatic hypertrophy during partial exclusion of
      bile-pancreatic juice in rats.
AB  - The time course of recovery from hypertrophied pancreas to the normal size was
      examined and compared with the time course of normal size pancreas getting
      hypertrophied in rats. The bile-pancreatic duct was cannulated and bile
      pancreatic juice was partly bypassed the proximal intestine. Trypsin and bile
      salts disappeared from the lumen of proximal quarter of intestine during the
      first 7 postoperative days; however, these appeared again after the 14th
      postoperative day and luminal trypsin activity reached 3 to 4 times the control
      level during the postoperative days 14-56. Conversely, the plasma cholecystokinin
      (CCK) concentration significantly increased on day 7, then declined thereafter,
      and the mRNA level of CCK in the proximal intestinal mucosa increased and reached
      the maximal level on day 7. Pancreatic wet weight, as an index of size, was
      significantly increased and remained high on postoperative days 7-28, then
      returned to the control size on day 56. Therefore, it took 7 d for the pancreas
      to become hypertrophied by high circulating CCK, however the pancreatic size
      recovered to the normal size on the 56th postoperative day although the plasma
      CCK level decreased with the appearance of luminal bile salt and trypsin during
      postoperative days 14-56. In conclusion, it took longer for the hypertrophied
      pancreas to return to the normal size (14 or more d) than for the normal size
      pancreas to become hypertrophied (7d).

PMID- 7823416
TI  - Aerobic capacity of competitive ice hockey players 10-15 years old.
AB  - Oxygen uptakes (VO2) recorded at anaerobic threshold and at the end of a maximal
      exercise (VO2 max) and their relation to left ventricular function were analyzed
      in 11 young ice hockey players during an incremental exercise on a bicycle
      ergometer. The children, highly trained, participated annually during 6 years
      (from the age of 10-15 years) in laboratory tests. The maturative status of the
      subjects was evaluated from peak height velocity (PHV). Heart rate was recorded
      by electrocardiogram. Oxygen uptake, CO2 production, respiratory frequency,
      pulmonary ventilation (VE) were recorded at rest and every 30 s during exercise
      through a Rudolph valve connected to a calibrated oxycon gas analyser. The
      anaerobic threshold was determined by a non-invasive method from pulmonary
      ventilation curves. Left ventricular volumes at end-systole and end-diastole were
      obtained, at rest, by M mode echocardiography. Results showed that both VO2 at
      anaerobic threshold and VO2max were positively correlated with body mass or with
      age of PHV. The increments were constant from year to year. At anaerobic
      threshold, the ratio VO2/VO2max was independent of maturative age. Similar
      findings were observed when considering VE except after the years of PHV where
      there was a remarkable increase in pulmonary ventilation. The results indicate
      that the growth of each cardiorespiratory component is optimalized with body size
      increase in order to keep constant the aerobic response to exercise. As judged by
      the explained variance of the different linear regression analyses between
      resting left ventricular dimensions and VO2, cardiac volume was of minimal
      importance in determining VO2. In the postpubertal period, stroke volume
      accounted for 26.7% of VO2 at anaerobic threshold and 30.0% of VO2max. This
      suggests that local changes occurring at muscular level are of paramount
      importance in determining the aerobic capacity of highly trained boys.

PMID- 7823417
TI  - Open-field behavior of rats following intracerebroventricular administration of
      neuromedin B, neuromedin C, and related amphibian peptides.
AB  - Neuromedin B (NMB) and neuromedin C (NMC) have amino acid sequences similar to
      those of various amphibian skin peptides and thus may elicit behavioral effects
      similar to those of bombesin. The present study was performed to determine the
      central effects of neuromedins (including pyro-NMB and pyro-NMC) in comparison
      with those of amphibian peptides using an open-field test situation. At 1 min
      after intracerebroventricular administration of the peptides, there was a marked
      decrease in the duration of locomotion, the distance moved, and rearing behavior,
      but a marked increase of excessive grooming and violent scratching. Pronounced
      behavioral changes were still observed 30 min after injection of the peptides,
      except for NMB. Thus, NMB seemed to be rapidly degraded by endogenous peptidases
      in the brain, suggesting that it might be the essential form of this neuropeptide
      family in the mammalian brain.

PMID- 7823418
TI  - Effects of lowering external Na+ concentration on cytoplasmic pH and Ca2+
      concentration in mouse pancreatic beta-cells: mechanism of periodicity of spike
      bursts.
AB  - The periodic spike-burst response of pancreatic beta-cells varies in duration
      with an increase of external glucose within the range 5-20 mM. To elucidate the
      mechanism determining the length of spike-burst, we studied the low-Na+ induced
      change in electrical response to glucose which is similar to the change induced
      by high glucose. Cytoplasmic pH (pHi) and Ca2+ concentration ([Ca2+]i) were
      measured by the microfluorometric method under normal and low-Na+ conditions in
      mouse pancreatic islets. Lowering external Na+ concentration from 135 to 25 mM by
      replacing Na+ with Tris+ induced progressive alkalinization in islet cells in the
      presence of 11.1 mM glucose. In contrast, reduction of external Na+ by
      replacement with Li+ caused intracellular acidification. Both manipulations
      described above caused a marked increase in [Ca2+]i, suggesting the presence of
      Na+/Ca(2+)-antiport activity. Although the change in pHi induced by decreasing
      external Na+ varied in direction depending on the species of cations used for
      replacing Na+, the pattern of electrical activity consistently changed from the
      spike-burst type to the continuous spike-generation type without regard for the
      difference in species of cations replacing Na+. These findings lead to the
      following hypothesis: A decrease in Na+ influx could cause a decrease in ATP
      consumption by Na+/K(+)-pumps that prevents the fall of intracellular ATP
      concentration. The resultant continuation of high concentrations of intracellular
      ATP may be responsible for the abolishment of the silent phase.

PMID- 7823419
TI  - Oscillatory contraction of single sarcomere in single myofibril of glycerinated,
      striated adductor muscle of scallop.
AB  - Unloaded contraction of a single sarcomere was studied on fiber fragments (1
      micron thick, 4- to 6-microns wide, and less than 50 microns long) from
      glycerinated scallop striated muscle. The fragment was activated from rigor by a
      rapid solution exchange method. Sarcomere length (SL) was measured in the
      intensity profile caused by scanning the phase-contrast image of the striation of
      the fragment every 5.4 ms using an optical scanner-photomultiplier system with an
      accuracy of 0.04 micron. The sarcomere started to contract with a latency of 44
      +/- 11 ms (mean +/- SD, n = 21) after the solution change. Averaging a few SLs in
      a fragment clearly revealed a phase, in which shortening was close to zero,
      preceded and followed by a rapid shortening phase. The contraction of a single
      sarcomere appeared to occur in an oscillatory manner with one or more of the zero
      velocity phases during the observed period (up to 250 ms) when the data points
      were approximated with a polynominal curve. The distance between the near zero
      velocity phases was 0.17 +/- 0.09 micron (n = 18). As the contraction was
      approximated with a staircase pattern consisting of a rapid shortening and a zero
      velocity phase, the duration of the zero-velocity phase was 44 +/- 18 ms (n =
      23). The velocity and the extent of the rapid shortening phase were 19.0 +/- 7.9
      microns/sarcomere (n = 29) and 0.16 +/- 0.06 micron (20 degrees C), respectively,
      both of which were independent of the SL examined (1.7-2.6 microns). The velocity
      in the shortening phase was independent of the extent of the shortening but
      decreased with increasing duration of the shortening phase. Probably because of
      the loss of light chains relating to the Ca-regulation from some myosins during
      preparation, an increase in the concentration of ATP in the absence of Ca2+
      resulted in a single shortening step of the sarcomere with a latency of 82 +/- 23
      ms, followed by a phase of little shortening; the velocity in and the extent of
      the shortening step were 12.8 +/- 8.4 microns/s/sarcomere (n = 5) and 0.12 +/-
      0.04 micron, respectively. The mechanism underlying the observed oscillatory
      contraction was considered in terms of the cross-bridge mechanism.

PMID- 7823421
TI  - An emergency nurses day celebration for children.

PMID- 7823420
TI  - Pretreatment with porcine relaxin and Mg ions enhances inhibitory effects of
      dibutyryl cyclic AMP in longitudinal muscle of estrogen-treated rat myometrium.
AB  - Phasic contractions were evoked in Mg-free Krebs solution by electrical
      stimulation in the longitudinal myometrial strip taken from estrogen-treated
      rats, and the application of 30 microM dibutyryl cyclic AMP (db cAMP) for 15 min
      depressed the amplitude of contraction to 81 +/- 18% (+/- SD, n = 23) of the
      control. The contractile depression caused by db cAMP was not significantly
      altered by pretreatment with either 1 mM Mg (40 min) or 100 mU porcine relaxin
      (15 min) alone; however it was markedly enhanced to 22 +/- 30% (n = 7) of the
      control response by the combined pretreatment with Mg and relaxin. The
      enhancement lasted for longer than 2 h thereafter in Mg-free Krebs solution. It
      was discussed that some memory factor was induced by relaxin in the presence of 1
      mM Mg to respond strongly to db cAMP.

PMID- 7823422
TI  - A look at our new emergency department: Medical University of South Carolina
      ACCESS Center, Charleston, South Carolina.

PMID- 7823423
TI  - A look at our new emergency department: LaGrange Memorial Hospital, LaGrange,
      Illinois.

PMID- 7823424
TI  - Causes of and remedies for customer dissatisfaction in Canadian emergency
      departments.

PMID- 7823425
TI  - October rescue.

PMID- 7823426
TI  - Who should ask for authorization to treat?

PMID- 7823427
TI  - Standing trauma orders should also be cost-effective.

PMID- 7823428
TI  - A new strategy for treating self-destructive substance abusers.

PMID- 7823429
TI  - High-pressure injection injury of the hand: a surgical emergency.

PMID- 7823430
TI  - Emergency department patient throughput: a continuous quality improvement
      approach to length of stay.

PMID- 7823431
TI  - An emergency nurse's experience with a traveling medical van.

PMID- 7823432
TI  - Abuse of women by male partners: basic knowledge for emergency nurses.

PMID- 7823433
TI  - Preterm labor: update on assessment and management.

PMID- 7823434
TI  - Nonlicensed, multiskilled workers in the emergency department: one hospital's
      experience.

PMID- 7823435
TI  - Emergency care for occupational exposures.

PMID- 7823436
TI  - Case studies in work redesign: "do-it-yourself" redesign.

PMID- 7823437
TI  - Physicians on scene: blessing or burden?

PMID- 7823438
TI  - Restraint and seclusion record.

PMID- 7823439
TI  - The team approach to emergency department overcrowding.

PMID- 7823440
TI  - Systems analysis: a baseline.

PMID- 7823441
TI  - Medication administration: potential liability.

PMID- 7823442
TI  - Improving documentation with a mock trial.

PMID- 7823443
TI  - Food-induced anaphylaxis in children.

PMID- 7823444
TI  - Trauma in a reformed health care environment.

PMID- 7823445
TI  - A 32-year-old man with spinal injury.

PMID- 7823446
TI  - Deputy coroner: a different kind of nursing. Interview by Marlene Jezierski.

PMID- 7823447
TI  - The kiss.

PMID- 7823448
TI  - 1842--a landmark in nephrology: Carl Ludwig's revolutionary concept of renal
      function.

PMID- 7823449
TI  - [Use of intraorganic electrophoresis in the treatment of peritonitis in
      children].
AB  - There were examined 53 patients aged from 1 to 14 years. The galvanization of an
      abdomen method with the help of current while preliminary intravenous and
      intraperitoneal antibiotics injection was used in the treatment of 21 patient. It
      permitted to avoid the relaparotomy conduction, to reduce the postoperative
      complications appearance frequency, and also to shorten the duration of hospital
      stay.

PMID- 7823450
TI  - [Use of open method of treatment in diffuse purulent peritonitis in children].
AB  - Open method of treatment--laparotomy--was used in 22 children with diffuse
      purulent peritonitis, aged from 1 to 14 years. This permitted to drain adequately
      the abdominal cavity after the operation, to abolish the intoxication during 2-3
      days in the most observations, to eliminate the enteroparesis. The single
      repeated abdominal cavity sanation was sufficient in 19 (90.5%) children, in 2
      she was applied twice. Laparostoma was closed in 17 (80.9%) patients on the 2-3
      th day, in 4--on the 4-7 th day after the operation. One child (4.5%) died.

PMID- 7823451
TI  - [Use of applied sorbents in ambulatory surgery in children].

PMID- 7823452
TI  - [Diagnostic errors in diseases of the abdominal cavity and retroperitoneal space
      in children].
AB  - The results of analysis of the diagnosis disjunction in 544 (17.2%) operated
      children, revealed for the period of 10 years, were adduced. The differential
      diagnosis mistakes of an acute appendicitis versus the other surgical pathology
      of abdominal cavity and retroperitoneal space were stipulated by objective (the
      peritonitis existence) and subjective (insufficient examination of the patient)
      reasons.

PMID- 7823453
TI  - [Follow-up results of modified Glenn-Andersen operation in children with primary
      vesicoureteral reflux].
AB  - The results of operative treatment of 51 patients with primary vesico-ureteric
      reflux followed from 6 mos to 11 yrs were analyzed. Glenn-Andersen method
      modification of clinic was used. Conclusion was made about the advantages of one
      moment bilateral ureters transplantation over the staged treatment in children
      with bilateral vesico-ureteric reflux. Good result was noted in 57 (77%)
      observations after 74 plastic operations.

PMID- 7823454
TI  - [Errors and hazards of injuries of the intestine during surgery of the kidneys
      and urinary tract in children].
AB  - The results of 7 observations of duodenum, colon and rectum injuries while
      urologic operations conduction are adduced. On the author's opinion, the
      principal method of treatment is the intestinal contents diversion.

PMID- 7823455
TI  - [Choice of the method of surgical treatment of hydronephrosis due to congenital
      stenosis of the pyeloureteral segment].
AB  - The results of treatment of 139 patients with congenital pyelo-ureteric segment
      (PUS) narrowing were analyzed. Plastic operation was conducted in 117 of them,
      PUS plasty with the flap application--in 22. The prognostic significance of
      sign's norm deviations of the PUS diameter and length ratio as a risk factor was
      studied to substantiate the numerical criterion--of operation method choice. In
      accordance with this prognostic significance the value of Student's criterion was
      calculated. When the value of ratio is no more than 0.3--the narrowed part
      resection with subsequent ureteropelviostomy is indicated, and when this value is
      0.31 or more--the PUS plasty with the flap application.

PMID- 7823456
TI  - [Esthetic effects of surgery in hernia of the anterior abdominal wall in
      children].
AB  - The cosmetic effect of operative interventions for the anterior abdominal wall
      hernia, vaginal process of peritoneum anomalies in 558 patients aged from 7 to 27
      years was studied. The 15-year follow-up was available. Poor cosmetic results
      appropriateness were determined, the advantages of the sutureless abdominal wound
      closure were examined, an operative accesses for the umbilical hernia and the
      hernia of linea alba treatment were proposed.

PMID- 7823457
TI  - [Dermoid and epidermoid cyst].
AB  - The treatment experience of 205 children aged from 1.5 mos to 14 yrs with dermoid
      or epidermoid cyst was summarized. The external localization was noted in 196
      (95.6%) children, internal--in 9 (4.4%). The difficulties most frequently
      occurred while differential diagnosis conduction of the tumor-like neoplasms,
      localized in the region of the nose bridge and on the anterior neck surface. The
      cyst relapse occurred in 2 (1%) children, during the operative intervention
      conduction the cyst capsule integrity was broken and, may be, all of her
      membranes were not dissected completely. The cyst malignancy was not noted.

PMID- 7823458
TI  - [Diaphragmatic cyst in children].
AB  - The experience of treatment of 4 children with nonparasitic diaphragmatic cyst
      was summarized. The informatic diagnostic methods are--ultrasonography of the
      thoracic and abdominal cavity organs, and in the cyst presence--sceletotopy in
      the hepatic segments projection, roentgenography, roentgenoscopy,
      pneumoperitoneum, pneumothorax. All the patients were operated on. The cyst had
      the right-sided localization, in 2 observations the mesothelial cyst was
      diagnosed, and in 2--the cystic teratoma of diaphragm.

PMID- 7823460
TI  - [Surgical treatment of patients with gastrointestinal ulcer hemorrhage and
      concomitant diabetes mellitus].
AB  - The results of surgical treatment of 800 patients with ulcer gastroduodenal
      bleeding, in 122 of whom diabetes mellitus was diagnosed, were analyzed.
      Organpreserving operations combined with vagotomy were conducted to the whole of
      the patients, the elaborated in clinic individualized approach to the diabetes
      mellitus prophylaxis was used. The glucose-correcting therapy methods were
      depicted with the respect to diabetes mellitus form, hemorrhage severity and
      indications for the operation.

PMID- 7823459
TI  - [Postoperative peptic ulcer in emergency surgery].
AB  - The experience of treatment of 36 patients with peptic postoperative ulcer,
      admitted to clinic in urgency, was analyzed: 29--with bleeding, 6--with the
      pronounced pain syndrome, 1--with perforation of ulcer. The conservative therapy
      conduction permitted to stop the bleeding and to abolish the pain syndrome, but
      the stable epithelialization of ulcers couldn't be achieved. Transthoracic
      supradiaphragmatic truncal vagotomy is the operation of choice for the treatment
      of peptic ulcer caused by inadequate stomach resection extent. All the patients
      recovered.

PMID- 7823463
TI  - [Different localizations of postburn esophageal stricture].
AB  - The results of 154 postburn strictures observations were analyzed. By the
      author's opinion, the appearance of stricture in retrocardial segment is caused
      by the esophageal blood supply peculiarities. Mainly retrocardial localization of
      the stricture appearance is caused by slowing here of regenerative process of
      dense cicatricial tissue formation due to poor blood supply of this esophageal
      segment, more pronounced microcirculation disorders and local tissue hypoxia.

PMID- 7823462
TI  - [Treatment of postoperative peritonitis].
AB  - The results of 123 relaparotomies conducted for the postoperative peritonitis
      after an urgent and planned operations on the abdominal cavity organs were
      analyzed. Clinical manifestations, the effectiveness of an early diagnostics
      methods, methods of mathematical prognosis and treatment, and also the
      immunological disorders occurring in postoperative peritonitis were studied. The
      mortality rate was 36.5%.

PMID- 7823461
TI  - [Determination of the risk of acute gastrointestinal ulcer hemorrhage].
AB  - The case records of 389 patients with ulcer disease were analyzed. The disease
      course was complicated by the profuse ulcer bleeding in 166 observations. There
      were no data available concerning hemorrhage in the anamnesis of 229 patients. As
      a result of statistical discriminant analysis of the bleeding and nonbleeding
      ulcers clinical picture peculiarities been made, 15 prognostically significant
      signs were chosen, they were quantitatively assessed and the risk of profuse
      bleeding appearance was determined. The results were confirmed in the 95% of
      observations.

PMID- 7823464
TI  - [An agent imparting antimicrobial properties to woven materials].
AB  - The proposed agent for the woven materials impregnation gives them antibacterial
      properties concerning gram-negative and gram-positive microflora, and have also
      the fungicidal activity. It high effectiveness testifies the vast resources of an
      agent in the treatment and prophylaxis of surgical pyo-inflammatory infection.

PMID- 7823465
TI  - [Effects of intravenous transfusion of lactosorbal on the course and outcome of
      experimental hemorrhagic shock].
AB  - Severe hemorrhagic shock was simulated in experiment on 5 dogs. The intravenous
      transfusion of a complex action hemocorrector Lactosorbal in the dose of 10 ml/kg
      provided the cardio- and haemodynamics indexes restoration, carbohydrate
      metabolism and acid-base equilibrium normalization, what promoted an experimental
      animals survival. Possible mechanisms of therapeutic action of preparation were
      considered.

PMID- 7823466
TI  - [Effects of carbacholine and noradrenaline on tissue reactions in healing of skin
      wounds].
AB  - In experiment on 15 rats, used as a skin wound models, it was established that
      under the carbachol (CC) influence the inflammatory reaction, granulation tissue
      development and the degree of her vascularization are intensified, and under the
      influence of norepinephrine (NE)--are reduced. And vice versa: the
      fibrillogenesis and the regenerated connective tissue resimulation processes are
      hold back under the CC action and are stimulated under the NE influence. On the
      initial stages of the wound healing CC and NE stimulate the epiderm regeneration.
      But while the CC application the epithelial lining of necrotized tissues then are
      destructed.

PMID- 7823467
TI  - [Splenic dysfunction in shock and its significance in the pathogenesis of
      traumatic disease].

PMID- 7823468
TI  - [Malignant tumors of the liver in children].
AB  - The treatment results of 65 children with malignant tumors of liver for the 1972
      1992 yrs period were analyzed. Hepatocellular cancer was diagnosed in 31,
      hepatoblastoma--in 23, poorly differentiated sarcoma, angiosarcoma, cancer
      sarcoma--in 11. Operations were conducted in 38 (58.5%) patients, of whom radical
      -in 22; the right-sided hemihepatectomy--in 14 (in expanded and expanded
      combined), left-sided--in 2, nonanatomical resection--in 6.
      Laparothoracophrenotomy was done in 8 children with massive tumor for the right
      sided hemihepatectomy conduction (in 2--with diaphragm resection and vast defect
      plasty with the help of a capron mesh). Of 22 radically operated children 4
      (18.2%) died: after the right-sided expanded hemihepatectomy conduction--3,
      nonanatomical liver resection--1. One more child with a massive tumor died during
      mobilization of the liver right lobe. Of 18 discharged children 12 died during
      following 18 mos, 6 survived. Five-year survival was 23.5%.

PMID- 7823469
TI  - [Closed trauma of the left kidney simulating splenic rupture and intraabdominal
      hemorrhage].

PMID- 7823470
TI  - [Chronic stomach volvulus in an infant].

PMID- 7823471
TI  - [Aorto-intestinal bleeding in a child].

PMID- 7823472
TI  - [Perforation of the cecum by a foreign body of organic origin in a child].

PMID- 7823473
TI  - [High retrograde invagination of the jejunum in the early postoperative period].

PMID- 7823474
TI  - [Method of drainage of the common bile duct].

PMID- 7823475
TI  - [Method of performing biliodigestive anastomosis].

PMID- 7823476
TI  - [Method of frame fixation of drainage during performance of choledochoduodenal
      anastomosis].

PMID- 7823477
TI  - [Surgical treatment of varicocele in children].

PMID- 7823478
TI  - [Benign neoformations of the liver in children].

PMID- 7823479
TI  - [Acute distension of the stomach in a child].

PMID- 7823480
TI  - [Acute appendicitis and situs inversus in a child].

PMID- 7823481
TI  - [Phlegmonous cholecystitis in a child].

PMID- 7823482
TI  - [Abscess of the recto-uterine excavation in a newborn infant].

PMID- 7823483
TI  - [Clinical aspects and surgical treatment of epidural hematoma in preschool
      children].

PMID- 7823484
TI  - [Case report of thoraco-abdominal injuries].

PMID- 7823485
TI  - [Use of lasers in the treatment of bronchopulmonary metastases of osteogenic
      sarcoma].

PMID- 7823486
TI  - [Diagnosis and treatment of giant posttraumatic hemangioma of the knee joint].

PMID- 7823487
TI  - [Hemodynamic criteria of prognostication of the outcome in revascularization of
      the lower limbs in severe ischemia].
AB  - Experience of surgical treatment of 166 patients with severe lower limbs ischemia
      is summarized. The parameters of regional hemodynamics got with the help of
      ultrasound dopplerography, electro-magnetic flowmetry, percutaneous pO2
      monitoring in the foot skin and registration of peripheral resistance of artery
      in distal anastomosis zone were used for prognostication of the vascular
      transplant function while aorto-femoral and femoro-popliteal segments
      reconstruction. The choice of surgical procedure tactics in accordance with
      prognosticated outcome permitted to lower the prevalence of an early
      postoperative complications from 17 to 8.4%.

PMID- 7823488
TI  - [Current aspects of prognostication of postoperative thromboembolic
      complications].
AB  - Seven most informative prognostic factors were chosen on the basis of analysis of
      clinical and laboratory investigation done with the use of modern computer
      methods: the principal illness character, patient's age, the presence of
      concomitant cardiovascular disease, obesity, the operative procedure duration,
      the homeostasis state and the volume of operative procedure. Decisive rule of the
      individual preoperative prognosis of postoperative venous thrombosis was
      elaborated and practically used with 76% reliability.

PMID- 7823489
TI  - [Extravascular compression of visceral arteries in the diaphragmatic segment of
      the aorta].
AB  - There were 140 patients operated for the celiac trunk (CT) and renal arteries
      extravascular compression (FC) in diaphragmatic aorta segment. The clinical
      syndromes of chronic abdominal ischemia and vasorenal hypertension were depicted.
      The predisposing factors of CT EC is the patients' dolichomorphic constitution
      with epigastric angle of < or = 70 degrees. The effectiveness of differentiated
      tactic choice of operative intervention magnitude according to the disease stage
      was shown. The late follow-up results witnesses the necessity of timely and
      adequate treatment.

PMID- 7823490
TI  - [Combined laser therapy of diabetic gangrene of the lower limbs].
AB  - Results of treatment of 130 patients with diabetic gangrene, whom the lower limb
      amputation on various levels was conducted, are adduced. In 58 patients the
      surgical treatment together with combined use of laser was conducted:
      intravascular irradiation of blood, high-powered laser Application while
      amputation performance and after it--percutaneous irradiation of amputation
      stump. Laser use promotes the improvement of immediate results of treatment and
      decrease of its duration.

PMID- 7823491
TI  - [Use of vasoprostan in the treatment of obliterating atherosclerosis of the lower
      limbs].
AB  - Reconstructive operations on the vessels is the principal method of treatment in
      patients with obliterating atherosclerosis of the lower limbs arteries. However
      in chronic arterial insufficiency of the III-IV stages the blood flow restoration
      is succeeded only in 60-75% of patients. Experience of firm "Shwartz" preparation
      "Vasoprostan" application possessing vasodilative and thrombolytic action in 47
      patients is summarized. The results obtained give evidence of high effectiveness
      of the preparation in conservative treatment of critical arterial ischemia of
      limb tissues.

PMID- 7823492
TI  - [Possibilities of radionuclide study methods in complex assessment of the state
      of ischemic segment of the limb].
AB  - Complex investigation of 122 patients with various degree ischemia of lower limbs
      was conducted. The site of the blood flow disorder in local arterial basins, the
      type of lesion (stenosis, occlusion, aneurysm or their combination), the degree
      of collateral blood flow compensation and the trophic changes of ischemized
      tissues were truthfully established with the help of radionuclide investigation.

PMID- 7823493
TI  - [Effects of sound vibration on the state of peripheral blood circulation in
      patients with obliterating atherosclerosis of the lower limbs].
AB  - In 31 patients with obliterating atherosclerosis of the lower limbs the heat
      irradiation changes under the influence of sound vibration with 2.5 kHz and 0.66
      W/cm2 intensity were studied. The durable effect of the combined application of
      therapeutic treatment and "vibrotherapy" was noted.

PMID- 7823494
TI  - [Use of several microvascular flaps in replacement of extensive suppurative
      necrotic defects of the supporting surface of the foot: transplantation of a
      double shin-foot flap].
AB  - The scheme of conduction of the microvascular transplantation using double flap
      of shin and foot combined with musculus serratus anterior is adduced. The double
      combination consists of the transplant of medial shin surface and medial plantar
      fragment. The advantages of the proposed method (availability of thin hypodermic
      base, own sensitive nerve, united blood supply system, and also long vascular
      pedicle, resistance for the exercise load, possibility of linking up of the third
      complex, and, perhaps, minimal harm done to donor region) contrary to the
      transplantation of a piece transplant having large dimensions permit to apply
      more effectively the double flap for the supporting points of foot substitution.

PMID- 7823495
TI  - [Pathogenesis, indications and choice of surgical treatment method in juxta- and
      suprarenal aortic aneurysm].
AB  - Experimental part of the work included the aortic aneurysm simulation in animals
      and the studying of the disease course. The results of observation of 12 operated
      on in clinic and 17 nonoperated patients are presented. Pathogenesis of the
      disease was studied, indications for the operation and the criterions of the
      treatment method choice were determined.

PMID- 7823496
TI  - [Iatrogenic injuries of blood vessels].
AB  - Results of treatment of 92 patients with nonpremeditated iatrogenic injuries of
      the circulatory vessels were analyzed. As a rule, the cause of injury were
      operative-technical mistakes. Classification of iatrogenic injuries of vessels is
      presented, several clinical observations are depicted in detail. By the authors
      opinion, the conduction of training of general surgeons for the issues of
      emergent angiosurgery is necessary.

PMID- 7823497
TI  - [Clinical use of artificial heart valve PLANIKS].
AB  - The first clinical results of a new repeated-disc artificial heart valve PLANIKS
      application were summarized. In prosthesis the useful hydrodynamic parameters,
      durability, reliability, convenience and easiness while implantation conduction
      are combined harmoniously, the sterility is guaranteed. PLANIKS permits to
      correct adequately the hemodynamics disorders in the early postoperative period
      and may be recommended for the clinical practice use.

PMID- 7823498
TI  - [Anatomical characteristics of the aortic valve in Laubry-Pezzi anomaly].
AB  - The aortal valve anomaly was studied in 179 patients using intraoperative
      examination and morphometry and histologic investigation of an excised cusps. The
      pronounced form and size asymmetry of the valve cusps revealed in Laubry-Pezzi
      syndrome and also histologic signs of their primary hemodynamic traumatization
      causes the predisposition for the progress of the aortal valve insufficiency,
      development of infectious endocarditis and rheumatism.

PMID- 7823499
TI  - [New biological vascular prosthesis made of avian trachea].
AB  - New biologic prosthesis of the arterial vessels manufactured of the bird trachea
      was elaborated and approved upon the test bench and experimental conditions.
      Sufficient mechanical durability and elasticity of the prosthesis was
      ascertained, alike the possibility of his application for the arterial vessels
      replacement. New bioprosthesis have such advantages as handiness at work,
      steadiness for twist and deformation, negligible thrombogenicity, relatively high
      endothelialization speed, functioning stability and nonreactivity.

PMID- 7823500
TI  - [Students and the 5 days].

PMID- 7823501
TI  - [Method of "discussional questioning"--one of many elements of problem-related
      teaching in the clinic of surgical diseases].

PMID- 7823502
TI  - [Current methods of the treatment of diabetic angiopathies of the lower limbs
      complicated by pyo-necrotic lesions].

PMID- 7823503
TI  - [Prevention of surgical wound suppuration after appendectomy].

PMID- 7823504
TI  - [Use of loading renography in prognostication of results of the surgical
      treatment in renovascular hypertension].
AB  - In 22 and 19 patients with vasorenal hypertension the influence of exercise
      loading and capoten action on renal function accordingly were analyzed using the
      data obtained with the help of radionuclide renography. In 10 (45.4%) of 22
      patients after the bicycle ergometry application the changes in hippuran
      transport occurred, in 12 (54.6%) the significant changes of renal function was
      not determined. In patients of these groups the arterial pressure after operation
      was accordingly 24.0/14.7 kPa (180/110 mm Hg) and 18.7/10.7 kPa (140/80 mm Hg).
      According to the data obtained with the help of radionuclide renography the curve
      height lowering was noted in 7 (36.9%) of 19 patients, and after capoten
      injection--in 18 (94.7%).

PMID- 7823505
TI  - [Method of limb amputation at the hip level].

PMID- 7823506
TI  - [Method of administration of regional chemotherapy in patients with high diabetic
      gangrene of the lower limbs].

PMID- 7823507
TI  - [2 cases of injuries of the thoracic aorta].

PMID- 7823508
TI  - [Use of transcutaneous electrophoresis of thiophosphamide in multimodal treatment
      of malignant tumor of the breast].

PMID- 7823509
TI  - [Use of modifiers in the treatment of the edematous-infiltrative form of breast
      cancer].

PMID- 7823510
TI  - [A rare complication after gastrectomy].

PMID- 7823511
TI  - [Non-Hodgkin's lymphoma of the appendix in a child].

PMID- 7823512
TI  - [Multiform tumor of the retroperitoneal space].

PMID- 7823513
TI  - [Malignant fibrous histiocytoma of the retroperitoneal space of the small
      pelvis].

PMID- 7823514
TI  - [Demon-Meigs' syndrome].

PMID- 7823515
TI  - [Abscess of single kidney complicated by acute perinephritis and diffuse
      peritonitis].

PMID- 7823516
TI  - [Tactics of treatment of patients with atherosclerotic circulatory
      encephalopathy].
AB  - Immediate and late follow-up results of nonoperative and operative treatment of
      244 patients with atherosclerotic dyscirculatory encephalopathy (ADE) were
      analyzed. The effectiveness of operative treatment is 1.9 times the non-operative
      one. Surgical correction of ADE of the I-II stages is mostly prognostically
      favourable. Operative intervention in patients with ADE of the III stage is
      justified if the operation risk is lower than the risk of disease progress.
      Indications for the operative treatment in patients with ADE caused by stenosing
      lesions of the main head arteries are elaborated.

PMID- 7823517
TI  - [Importance of an intact posterior capsule for the vitreous body. Complication of
      posterior capsulotomy].
AB  - The various extracapsular cataract surgery techniques keep the anatomy and
      physiology of the eye largely untouched, since both the intact posterior capsule
      and the crystalline lens form a diaphragm between the aqueous humour and the
      vitreous. If the posterior capsule opacifies--which occurs in up to 50% within
      five years postoperatively--a capsulotomy becomes necessary. This increases the
      rate of retinal detachment and cystoid macular edema. To date no pharmacologic or
      immunologic means exist to prevent posterior capsule opacification. Implanting
      the IOL into the capsule bag and the biconvex lens design by itself reduce the
      incidence of opacification. The biconvex optic of the IOL seals the gap in the
      capsule, if a capsulotomy has been performed; fluorophotometry shows us that the
      diaphragm function remains intact after in the bag implantation as compared to
      sulcus fixated IOL.

PMID- 7823518
TI  - [Phototherapeutic keratectomy].
AB  - BACKGROUND: In the last few years the excimer laser has been increasingly used
      not only for refractive surgery but also for therapeutic purpose. We report about
      our two year experience with this form of therapy. PATIENTS AND METHODS:
      Phototherapeutic keratectomy (PTK) has been performed on 27 eyes of 25 patients.
      The following diseases have been treated: Recurrent erosions (14), 9 of them in
      connection with bullous keratopathy, persistent epithelial defects (4), corneal
      opacity (6), one of them due to macular dystrophy, limbal infiltrates (2) and
      pterygium (1). RESULTS: 3 of 4 patients with persistent epithelial defects and
      92% of the recurrent erosions were treated successfully. Above all the treatment
      of recurrent erosions in connection with bullous keratopathy was very
      satisfactory. The patients with corneal opacity achieved a significant
      improvement of their visual acuity. CONCLUSION: The excimer laser is very
      suitable for therapy of different corneal surface pathologies. The possibility to
      treat painful bullous keratopathy is very encouraging.

PMID- 7823519
TI  - [Iris black diaphragm intraocular lenses in traumatic Aniridia].
AB  - PURPOSE: In this study we wanted to gain experiences with a new black diaphragm
      IOL concerning surgical postoperative difficulties in traumatic aniridia.
      PATIENTS: Since June 1991 we have implanted the IOL prototype and the
      modifications into 13 eyes with traumatic aniridia. The IOL was transsclerally
      sutured in 11 eyes without capsular support and it was positioned in front of
      capsular remnants in two eyes. In eight eyes penetrating keratoplasty was
      necessary. The mean follow-up period was 17 (1-34) months. RESULTS: The seventh
      IOL modification can be implanted safely now. Persistent intraocular inflammation
      (Tyndall +) has been observed in all eyes postoperatively but it seems to
      disappear slowly. Its effect upon the corneal endothelium and the development of
      cystoid macula edema is still under investigation. Secondary glaucoma has been
      the greatest postoperative problem: It could be controlled medically in five
      eyes, surgically in two eyes, but remained uncontrolled in one eye. Implantation
      of the IOL improved visual acuity in 11/13 eyes. CONCLUSION: Rehabilitation of
      eyes with traumatic aniridia by implanting the new black diaphragm IOL still
      presents some unsolved problems, especially uncontrolled secondary glaucoma and
      prolonged intraocular inflammation. In spite of many encouraging aspects we
      advise to be rather cautious and self-restrictive in this group of patients.

PMID- 7823520
TI  - [Effect of corneal collagen shields and epithelial growth promoting factors on
      epithelialization of the human cornea].
AB  - PATIENTS AND METHODS: In 28 patients after perforating keratoplasty followed by
      epithelial abrasion of the transplant the period required for epithelial closure
      with a therapy including collagen shields and the growth stimulating factors
      vitamin A and Epidermal Growth Factor (EGF) was determined. RESULTS: A
      significant acceleration of the epithelialization was observed in all groups
      treated with collagen shields compared to the control group. There is no
      significant difference between collagen shield application without additives and
      a therapy with collagen and EGF. Under collagen and retinyl palmitate therapy the
      epithelialization compared to collagen without additives as well as compared to
      collagen and EGF at a concentration of 100 ng/ml is significantly accelerated (p
      = 0.05). CONCLUSION: Collagen shields, especially combined with vitamin A and
      EGF, can be employed as a therapeutic concept offering accelerated epithelial
      wound closure after keratoplasty.

PMID- 7823521
TI  - [The COMOD system. A preservative-free multidose container for eyedrops].
AB  - BACKGROUND: The newly developed COMOD -system is a multi-dose-container for eye
      drops which makes the addition of preservatives unnecessary. In this study we
      investigated the microbiological safety of the COMOD -system which was used in
      action for the first time. METHODS: After cataract surgery 97 patients only used
      unpreserved, dexamethason-containing eye drops in COMOD -bottles for two days in
      hospital and for five more days at home. The used bottle were examined
      microbiologically afterwards. RESULTS: No COMOD -bottle showed a
      microbiologically serious contamination; no patient showed an unusual healing
      process which would have been typical for any infection. Concerning the handling
      it turned out during use in hospital that the hand-made prototypes have to be
      improves. The vast majority of patients managed the handling at home well,
      independent of sex or age. CONCLUSION: The COMOD -system is a suitable
      microbiologically safe container for unpreserved eye drops.

PMID- 7823522
TI  - [Physical and aerodynamic airflow relations of the air stream of the Micro-Air
      aesthesiometer].
AB  - BACKGROUND: In an experimental study we examined the aerodynamical
      airstreamprofile of a new airstream aesthesiometer. With this instrument it is
      possible to measure corneal sensitivity without touching the cornea. METHOD: A
      constant hotwire-anemometer was used to measure the 0.5 s air impulse in
      different distances. The corneal topographic sensitivity was measured at 45
      probands, age 20 to 80. RESULTS: The investigations show that the laminar air
      stream within the 0.2 mm wide nozzle changes after withdrawal, in regards to
      stream profile, jet width and speed. The parabolashaped stream profile passes
      over through the air matrix and changes into a bell-shaped profile. The stream
      properties of the circular free system imply that the air stream in a 4 mm
      distance is nearly half as wide and double as high or fast in comparison to an 8
      mm distance. The corneal sensitivity measured with the CMA showed in comparison
      to the Draeger aesthesiometer a lower sensitivity than in the periphery.
      CONCLUSION: A clinical use for measuring corneal sensitivity with the CMA can not
      be recommended.

PMID- 7823523
TI  - [Proliferative retinopathy in chronic myeloid leukemia].
AB  - BACKGROUND: In 50% of patients with acute and chronic myelocytic leukemia retinal
      alterations occur which are similar to those of nonproliferative diabetic
      retinopathy or hypertensive retinopathy. Retinal neovascularizations, however,
      are rarely seen and only found in patients with the chronic disease. PATIENTS AND
      METHODS: We report on the clinical course of three patients with advanced stage
      of proliferative retinopathy in CML. In two patients, the diagnosis of CML was
      established after ocular involvement. Therapy was planned according to the
      principles, which have proven effective in other vasoproliferative retinopathies.
      Eyes with neovascular changes were only treated by panretinal scatter
      photocoagulation of the avascular zones. In the cases with complications like
      vitreous hemorrhage and traction retinal detachment, vitreoretinal surgery was
      performed. RESULTS: Using this therapeutic principles in 4 of 6 eyes a visual
      acuity > 0.7 could be preserved. In three eyes impending macular involvement by
      traction retinal detachment was prevented. CONCLUSION: The therapeutic approach,
      which is valid for proliferative retinopathies of various etiology is also
      beneficial for ocular complications in CML.

PMID- 7823524
TI  - [Blue nevi of the conjunctiva].
AB  - PATIENT AND METHODS: A 54-year-old man presented with multifocal pigmentations of
      the left bulbar and palpebral conjunctiva. He had first noticed these changes 5
      years ago without any evidence of progression. The pigmented lesions were located
      in the plica, caruncle, the lower fornix and the mucocutaneous junction of the
      lower lid. The right cornea showed a focal superficial scar paracentrally due to
      a herpes simplex keratitis in 1970. Visual acuity was 20/20, otherwise the eyes
      were unremarkable. Biopsies were performed in all areas. One year after surgery,
      there was no recurrence of the lesions. MICROSCOPY: Histopathologically, the
      conjunctival epithelium is essentially unremarkable. The substantia propria
      display mostly uniformly pigmented spindle-shaped melanocytic cells. Many cells
      contain coarsely clumped melanin granules. Other areas reveal poorly pigmented to
      unpigmented melanocytic cells, some of them with Schwannian features.
      Intranuclear vacuoles are commonly present. The tumor cells are often located in
      stromal areas displaying increased amounts of collagen. A few polyhydral
      melanophages are present within the lesion. DIAGNOSIS: Biopsy A (plica)--blue
      nevus with areas of cellular blue nevus. Biopsy B (caruncle)--cellular blue
      nevus. Biopsy C (lower fornix)--cellular blue nevus. Biopsy D (mucocutaneous
      junction of left lower lid)--Blue nevus.

PMID- 7823525
TI  - [High-frequency oscillating ventilation in premature infants under 1500 gram
      birth weight].
AB  - In 58 premature infants with a birthweight < 1500 g High-Frequency-Oscillating
      Ventilation (HFOV) was initiated within the first 48 hours of life. Indications
      for HFOV were: no response to surfactant application (N = 41), respiratory
      distress syndrome without surfactant application (N = 9), pulmonary interstitial
      emphysema (N = 8). Mean gestational age of the enrolled patients was 27.6 weeks
      (24-32) and mean birthweight was 964 g (490-1450). 23 infants died, 5 from non
      pulmonary causes. Of the remainder 2 had B-Strept.-septicemia, 1 lunghypoplasia,
      and 1 patient died on the 70th day of life from chronic lung disease. There were
      no statistical differences between survivors and nonsurvivors in gestational age,
      birthweight, umbilical pH, 1 min APGAR score or time on conventional ventilation
      prior to HFOV. Alveolar-arterial-O2-difference dropped in the group of surviving
      patients from x487 mm Hg (sd +/- 60) to 252 mm Hg (sd +/- 89) after 6 hours (p <
      0.0001) and in the nonsurvivors from x517 mm Hg (sd +/- 74) to x373 mm Hg (sd +/-
      106) (p = 0.002). Oxygenationindex fell from x25 (sd +/- 10) to x5 (sd +/- 1.5)
      in the survivors and from 25 (sd +/- 11) to x9 (sd +/- 5.5) in the nonsurvivors
      within 6 hours (p < 0.0001). Mean airway pressure could be lowered in survivors
      from x7.6 cm H2O (sd +/- 0.6) to 5.3 cm H2O (sd +/- 0.8) and in nonsurvivors from
      x8.6 cm H2O (sd +/- 0.6) to 5.7 cm H2O (sd +/- 0.9) (p = 0.0002). The promising
      results of HFOV as a rescue therapy require a controlled study for its use as a
      primary mode of ventilation in premature infants.

PMID- 7823526
TI  - [Hemodynamic effects of high-frequency oscillating ventilation in preterm and
      term infants].
AB  - To study the effects of high frequency oscillating ventilation (HFOV) on cerebral
      and abdominal circulation we measured blood flow velocities in three cerebral
      arteries and in the A. mesenterica superior by pulsed doppler ultrasound in 13
      preterm (mean gestational age 28 weeks [25-31]) and 3 term infants during
      conventional ventilation (intermitted positive pressure ventilation, IPPV) and
      HFOV. In the preterm infants systolic blood flow velocities decreased under HFOV
      in all cerebral arteries. Statistically significant differences were found in the
      A. cerebri anterior (45.8 cm/s [sd +/- 20.6] versus 34.3 [sd +/- 10.8]; p < 0.02)
      and in the A. basilaris (52.8 cm/s [sd +/- 26.4] versus 44.1 [sd +/- 18.7]; p <
      0.05). There was also a distinct decrease of systolic blood flow velocity in the
      A. mesenterica (111 cm/s [ +/- 31.3] versus 61.8 cm/s [sd +/- 18.6]; p < 0.002).
      The enddiastolic blood flow velocity and the Resistance Index of Pourcelot did
      not change significantly. The systemic blood pressure did not change during
      conventional ventilation or HFOV. Mean airway pressure and pCO2 were lower during
      HFOV, but there was not strong correlation with the reduction of flow velocities
      in the studied arteries (r = 0.48). In the three term infants presenting with a
      persistent pulmonary hypertension of the newborn, there was an increase in
      systolic and enddiastolic flow velocities in all studied arteries under HFOV.

PMID- 7823527
TI  - [Obstructive apnea in premature and young infants].
AB  - The occurrence of obstructive apneas in premature and young infants is associated
      with a higher risk for SIDS. In order to assess the incidence of obstructive
      apnoeas in infants with different risk for SIDS pneumography was performed
      including the registration of the nasal air flow in 312 children: 69 preterm
      infants, 42 children after intensive care, one infant that later died of SIDS, 14
      children after ALTE, 84 children after apnoeas observed by their parents, 25
      siblings of SIDS-victims and 77 controls. Obstructive apnoeas were found in 24.6%
      of the preterm infants, in 28.5% of the children after intensive care, in 50% of
      the children after ALTE and in the one infant that later died of SIDS.
      Obstructive apnoeas however were registered only in 16.7% in the "apnoea-group",
      in 12% of the SIDS-siblings and in 11.7% of the controls. We therefore conclude
      that obstructive apnoeas which were observed more frequently in children with a
      higher risk for SIDS are of predictive value for the SIDS risk. Pneumography
      should therefore include the measurement of the nasal air flow. Home monitoring
      should be performed with devices that are able to assess bradycardias as indirect
      signs of obstructive apnoeas.

PMID- 7823528
TI  - [BCG-vaccination in neonates as a cause of osteomyelitis--an argument against BCG
      vaccination?].
AB  - BCG-osteomyelitis is a rare complication of BCG-vaccination. By means of a case
      report clinical and immunological findings are discussed. Contrary to the
      undramatic clinical symptoms the x-ray showed pronounced osteolytic lesions in
      the sternum. The bacteriological examination demonstrated mycobacteria of BCG
      type. Immunological investigations presented normal humoral and cellular
      immunity. The therapy (curettage, antituberculous drugs) was effective. In spite
      of this complication the BCG-vaccination is furthermore recommended.

PMID- 7823529
TI  - [Neonatal progeroid syndrome (Wiedemann-Rautenstrauch). A follow-up study].
AB  - The diagnostic criteria of the neonatal progeroid syndrome (NPS) are:
      intrauterine and postnatal growth failure, hydrocephalic appearance, prominent
      scalp veins, old-looking face, absence of subcutaneous fat and neonatal teeth.
      Until now altogether nine cases have been reported, which were predominant
      diagnosed in infant age. The NPS is in general assigned to the autosomal
      recessive trait. With increasing age the outward appearance stays unchanged. The
      in 1977 under diagnose progeria presented patient is now 16 years old. With her a
      considerable atactic movement disturbance developed next to a psychomotoric
      retardation. The change in metabolism of proteoglycane that was remarkable in
      infant age is now no longer provable.

PMID- 7823530
TI  - [De Barsy-Moens-Dierckx syndrome: unusual course in a neonate].
AB  - We report about a premature infant with a De Barsy-Moens-Dierckx-syndrome, which
      is a rare cutaneo-oculo-cerebral malformation-syndrome. It is defined by the
      combination of a progeroid aspect, cutis laxa, growth retardation, cornea
      clouding, mental retardation and athetoid movements. Furthermore, the reported
      case showed a remarkable thermolability and suffered from generalised seizures
      resistant to therapy. Despite extensive sonographic examinations the prepartal
      diagnosis seems to be very difficult.

PMID- 7823531
TI  - [Roberts syndrome with aneurysm of the interatrial septum, cow milk protein
      intolerance and absent swallowing reflex].
AB  - A three years old girl with Roberts-syndrome is presented in this report. An
      aneurysm of the interatrial septum without hemodynamic significance was found
      besides the typical symptoms of the Roberts-syndrome. The child had to be fed by
      nasogastral tube for more than two years because of never feeling hungry and
      lacking reflex to swallow. A pulmonary and intestinal reaction during the
      provocation with cowmilkprotein-containing food was observed additionally, so
      that we had to give an cowmilkprotein-free diet until the age of 28 months. The
      majority of reported cases with Roberts-syndrome showed characteristic
      cytogenetic abnormalities. The karyotype of our patient was normal. Roberts
      syndrome is an autosomal recessive disorder. We recommended repeated ultrasound
      examinations during the next pregnancy because of the 25% recurrence risk on
      subsequent siblings. The prognosis quoad vitam in patients with Roberts-syndrome
      remains poor. However, the development in our patient stresses the eminent value
      of medical and social support for those seriously handicapped children.

PMID- 7823532
TI  - [Congenital absence of the pectoral muscle with contralateral peromelia of the
      forearm].
AB  - Report of an imbecile female aged 20 years with congenital absence of the
      pectoral muscle (abortive Poland anomaly) at the right and peromelia of the left
      forearm.

PMID- 7823533
TI  - Amplification of selected exons by polymerase chain reaction enables
      determination of the translational reading frame of dystrophin mRNA resulting
      from deletion mutations.
AB  - Duchenne and Becker muscular dystrophies (DMD and BMD) are severe and mild
      phenotypes, respectively, of the mutated dystrophin gene. Based on the frameshift
      theory, an out-of-frame deletion causes DMD, while an in-frame deletion causes
      BMD. Amplification of deletion-prone exons by polymerase chain reaction (PCR) has
      been used for the screening of deletion mutations of the dystrophin gene.
      However, it is difficult to determine the resulting translational reading frame
      in deleted cases by amplification of the deletion-prone exons. To determine the
      resulting translational reading frame, we employed a method which selectively
      amplifies exons affecting the following translational reading frame. Using this
      method, thirty-three DMD/BMD patients with a deletion mutation in the central
      region of the dystrophin gene were examined. Twenty-seven of 29 DMD patients had
      out-of-frame deletions, while only two had in-frame deletions. All four BMD
      patients had in-frame deletions. Therefore, 93.9% patients fitted the frameshift
      theory. This method is very useful for clinical diagnosis because of its
      precision and convenience.

PMID- 7823534
TI  - ICAM-1 expression and cellular injury in cultured endothelial cells under
      hypoxia/reoxygenation.
AB  - Intercellular adhesion molecule 1(ICAM-1) expression and cellular changes in
      human umbilical vein endothelial cells(HUVEC) and ECV304, an established cultured
      line derived from HUVEC, under hypoxia and hypoxia(H)/reoxygenation(R) were
      investigated by immunological, cytochemical, and morphological methods. ICAM-1
      expression in HUVEC decreased slightly under hypoxia(92%) and was up-regulated
      under reoxygenation(114%), but this up-regulation was diminished by superoxide
      dismutase(SOD). The up-regulation of ICAM-1 expression by interleukin-1 beta(IL-1
      beta) was detected at almost equal levels under hypoxia, and H/R. Using lucigenin
      chemiluminescence, we demonstrated superoxide generation from HUVEC under H/R.
      The Ca2+ influx under hypoxia, and the Ca2+ release from the cells under H/R
      reduced by SOD were detected cytochemically. Vacuole formation as cell injury
      under hypoxia and H/R was detected by electron microscopy. The present findings
      provide evidence that superoxide generated from HUVEC is responsible for the up
      regulation of ICAM-1 expression under H/R, and the cause of endothelial cellular
      injury.

PMID- 7823535
TI  - Effect of nucleosides and a nucleotide mixture on proliferation of human gastric
      cancer cells (KATO III).
AB  - The effect of the nucleotides and a nucleotide mixture (OG-VI), consisting of
      inosine, guanosine 5'-monophosphate (5'-GMP), cytidine, uridine, thymidine (TdR)
      (4:4:4:3:1 in molar ratio), and TdR co-administration on proliferation of KATO
      III human gastric cancer cells in culture was evaluated. Consumption of purine
      and pyrimidine by cancer cells and changes in cell number with OG-VI or TdR were
      compared with the control culture medium (Williams E) after 72 hour-culture.
      Addition of OG-VI or TdR did not enhance the cellular proliferation, but
      inhibited growth when given in higher concentrations (0.3-3 mM inosine, 0.3-3 mM
      5'-GMP, 0.22-2.2 mM uridine, 74-740 microM TdR). Consumption rate of TdR in the
      medium was less in the TdR group, 33.7%, than in the OG-VI group, 72.2% (p <
      0.05). This suggests that TdR metabolism is modulated by other nucleosides and
      nucleotide included in OG-VI. Under the coadministration of 5-fluorouracil
      (FUra), addition of OG-VI or TdR suppressed cellular proliferation (p < 0.05).
      The inhibition rate of cellular proliferation in the OG-VI group was slightly
      higher than the TdR group, but there was no statistically significant difference
      between the two groups. The combination of FUra with OG-VI or TdR enhances the
      antitumor effect of FUra. It is concluded that the OG-VI does not enhance the
      tumor cell proliferation and it is a potential biochemical modulator of FUra
      metabolism in human cancer cells.

PMID- 7823536
TI  - Sweat testing for heroin, cocaine, and metabolites.
AB  - Although a variety of drugs have been detected in sweat, little information is
      available on the characteristics of drug excretion in sweat under controlled
      dosing conditions. A series of clinical studies were designed to determine the
      identity, concentration, time course, dose dependency, and variability of drug
      and metabolite excretion in sweat following administration of single doses of
      cocaine and heroin to human subjects. Sweat was collected by means of a sweat
      patch that could be worn for a period of several days to several weeks at a time,
      resulting in accumulation of drug in the patch. Sweat patches were removed at
      specified times and frozen until analyzed by gas chromatography--mass
      spectrometry. Cocaine and heroin were the major analytes excreted in sweat
      following their administration. Smaller amounts of cocaine metabolites were also
      detected following cocaine administration. 6-Acetylmorphine appeared rapidly
      after heroin administration and continued to increase while heroin content
      decreased, suggesting that heroin was undergoing hydrolysis in the sweat patch.
      Cocaine appeared in sweat within 1-2 hours and peaked within 24 hours in an
      apparent dose-dependent manner. Analysis of duplicate adjacent patches from
      individual subjects who had been administered cocaine provided similar
      quantitative results, suggesting that intrasubject variability was relatively
      low, whereas intersubject variability was high. These observations regarding the
      excretion of cocaine and heroin analytes in sweat have important forensic
      implications to other fields such as hair analysis. Sweat excretion could be an
      important mechanism by which drugs enter hair. These data also suggest that the
      sweat patch could serve as a useful monitoring device in surveillance of
      individuals in treatment and probation programs.

PMID- 7823537
TI  - Quality assurance in breath-alcohol analysis.
AB  - Evidential breath-alcohol testing requires an adequate quality assurance (QA)
      program to safeguard the testing process and validate its results. A
      comprehensive QA program covers (a) test subject preparation and participation;
      (b) the analysis process; (c) test result reporting and records; (d) proficiency
      testing, inspections, and evaluations; and (e) facilities and personnel aspects.
      Particularly important are the following necessary scientific safeguards as
      components of quality control: (a) a pretest deprivation-observation period of at
      least 15 minutes; (b) blank tests immediately preceding each breath-collection
      step; (c) analysis of at least duplicate breath specimens; and (d) a control test
      accompanying every subject test. These safeguards have withstood adversarial
      challenges in the judicial system for more than 30 years.

PMID- 7823538
TI  - Detection of benzodiazepines and tribenzazolams by TRIAGE: confirmation by solid
      phase extraction utilizing SPEC.3ML.MP3 microcolumns and GC-MS.
AB  - A new point-of-care urine drugs-of-abuse testing device, the BIOSITE TRIAGE, was
      evaluated for detection of benzodiazepines (BNZs). TRIAGE utilizes a unique,
      competitive, visual immunoassay methodology to simultaneously detect seven
      classes of drugs of abuse. Because of the unique ASCEND Multimmunoassay
      technology, conflicting results may arise when TRIAGE is compared with
      conventional immunoassay techniques. Apparent TRIAGE BNZ false-positive results
      may occur when gas chromatographic-mass spectrometric (GC-MS) confirmation
      utilizes oxazepam as the analyte used to confirm the presence of BNZs. TRIAGE BNZ
      results were correlated with those of Syva EMIT, (n = 106, overall agreement
      85%). Both negative and positive urine samples were tested by GC-MS for the
      following drugs: oxazepam, nordiazepam, desalkylflurazepam, OH-ethylflurazepam,
      lorazepam, temazepam, alpha-OH-alprazolam and alpha-OH-triazolam. Urine samples
      were extracted using the new ANSYS SPEC.3ML.MP3 solid-phase extraction
      microcolumn. The ANSYS procedure for BNZs was modified to include
      desalkylflurazepam, OH-ethylflurazepam, lorazepam, temazepam, alpha-OH
      alprazolam, and alpha-OH-triazolam. Deuterated oxazepam and alpha-OH-alprazolam
      were used as internal standards. Limits of quantitation (LOQs) ranged from 25 to
      100 ng/mL with a limit of detection of 25 ng/mL for all analytes. Individual
      analytes demonstrated within-run precision and between-run precision ranging from
      0.9 to 4.7% CV and 1.3 to 16.9% CV, respectively. All analytes were linear from
      their LOQs to 1000 ng/mL.

PMID- 7823539
TI  - Pharmacokinetics and pharmacodynamics of smoked heroin.
AB  - Despite the current popularity of smoking as a route of drug self-administration,
      there have been few human studies characterizing the pharmacokinetics and
      pharmacodynamics of smoked drugs of abuse. A variety of technological
      difficulties are encountered in the design of smoking studies, such as delivering
      reproducible doses and limiting the amount of pyrolysis of parent drug. As part
      of a concerted research effort to deliver precise, smoked doses of drug, a
      computer-assisted smoking device was utilized that delivered single puffs of
      heroin vapor to human subjects under controlled clinical conditions. Recovery
      studies indicated that the smoking device delivered approximately 89% of parent
      heroin to subjects. Although only two qualified heroin smokers could be
      identified as eligible volunteers, their participation provided the unique
      opportunity to study the pharmacokinetics and pharmacodynamics of smoked heroin.
      The two subjects were administered four smoked heroin doses in ascending order.
      In addition, four intravenous doses of heroin were administered for comparison of
      effects and estimation of bioavailability. Concurrent physiological, behavioral,
      and performance measures were collected along with blood samples. Blood was
      analyzed for heroin, 6-acetylmorphine, and morphine by solid-phase extraction gas
      chromatography-mass spectrometry. Heroin appeared rapidly in blood after
      administration and peaked 1-5 minutes after smoking, which is similar to that
      observed following intravenous administration. Heroin concentrations declined
      rapidly to the limit of detection (1.0 ng/mL) by 30 minutes. 6-Acetylmorphine
      blood concentrations also peaked and declined rapidly after smoked heroin with
      peak concentrations occurring at 1-2 minutes after smoking. Morphine levels rose
      and decayed more slowly. Mean elimination half-lives for heroin, 6
      acetylmorphine, and morphine were 3.3 min, 5.4 min, and 18.8 min, respectively,
      by the smoked route. The bioavailability of smoked heroin was highly variable.
      Physiological measures such as pupil diameter demonstrated a counterclockwise
      hysteresis compared with heroin blood levels. The rapid onset of pharmacological
      effects together with the early appearance of heroin and metabolites in blood
      following smoked heroin demonstrated the effectiveness of this route of drug
      administration. It is evident that the smoking route enables individuals to
      obtain similar pharmacological effects as are produced by intravenous
      administration of heroin.

PMID- 7823540
TI  - Amphetamine as an artifact of methamphetamine during periodate degradation of
      interfering ephedrine, pseudoephedrine, and phenylpropanolamine: an improved
      procedure for accurate quantitation of amphetamines in urine.
AB  - During periodate degradation of interfering ephedrine, pseudoephedrine, and
      phenylpropanolamine in the extraction of methamphetamine from urine, it was
      observed that a small amount of methamphetamine was demethylated to amphetamine.
      although all three interfering phenylpropanolamines could be degraded by
      periodate at pH 5.2 and above, this periodate-mediated transformation of
      methamphetamine to amphetamine was observed only at pH 9.1 and above. Therefore,
      to avoid this transformation, a pH of 6.2 was used for the oxidative degradation
      of phenylpropanolamines. The excess periodate was then reduced with thiosulfate
      or ascorbic acid prior to the extraction of methamphetamine using a basic pH.

PMID- 7823542
TI  - A mexiletine intoxication.
AB  - A case is presented of a 26-year-old white male with a history of depression and
      previous suicide attempts. No anatomic cause of death was determined at the
      autopsy. Comprehensive toxicological analysis of the blood and urine specimens
      identified mexiletine, a class 1B antiarrhythmic drug. Mexiletine was detected by
      gas chromatography and confirmed by gas chromatography-mass spectrometry.
      Quantitations were as follows: heart blood, 38 mg/L; subclavian blood, 14 mg/L;
      urine, 370 mg/L; liver, 190 mg/kg; kidney, 170 mg/kg; vitreous humor, 17 mg/L;
      and bile, 440 mg/L. The medical examiner ruled that the cause of death was
      mexiletine intoxication and the manner of death was suicide.

PMID- 7823541
TI  - Disposition of cocaine and norcocaine in blood and tissues of B6C3F1 mice.
AB  - The biodisposition of cocaine and norcocaine in blood and tissues of
      immunological importance in B6C3F1 mice following exposure to cocaine or cocaine
      plus an organophosphate esterase inhibitor, diazinon, is presented. Analysis of
      specimens was by gas chromatography-mass spectrometry. Results from these studies
      indicate that pretreatment with diazinon significantly increases cocaine and
      norcocaine concentrations in the blood, spleen, thymus, and liver. Following
      acute exposure to cocaine-diazinon, cocaine was found in the spleen and thymus up
      to 1 hour after exposure. Norcocaine was not detected at this time. Following 7
      day exposure to cocaine-diazinon, both cocaine and norcocaine were found in
      liver, blood, and spleen up to 1 hour after the last exposure; however, only
      cocaine was detected in the thymus at 1 hour. Cocaine and norcocaine were not
      detected in any tissues 24 hours after the last exposure.

PMID- 7823543
TI  - Benztropine identification and quantitation in a suicidal overdose.
AB  - For a human fatality involving suspected overdose with the anticholinergic agent
      benztropine, GC-MS analysis was utilized for identification, quantitation, and
      investigation of metabolism. Organic extracts of blood and urine were analyzed by
      a capillary-column gas chromatograph interfaced with an ion-trap mass
      spectrometer, which was programmed for wide-spectrum data acquisition. Electron
      impact and chemical ionization were used for benztropine detection. The chemical
      structures of the ion fragments are proposed. Benztropine-d3 was synthesized and
      used as an internal standard. Quantitative determinations of benztropine revealed
      0.183 mg/L in blood and 7.12 mg/L in urine from the decedent. Drug concentrations
      were interpreted relative to the case findings, published data, and a limited
      evaluation of the therapeutic concentrations in psychiatric patients. In
      addition, the possible metabolic conversion to norbenztropine was investigated by
      the synthesis of the norbenztropine derivative. Chromatographic evaluation of
      samples from the case study did not reveal significant bioconversion via the N
      desmethylation pathway.

PMID- 7823544
TI  - Postmortem distribution of mexiletine in a fatal overdose.
AB  - A case involving a fatal overdose of mexiletine is presented. Quantitation of the
      drug was accomplished by gas chromatography with a flame-ionization detector. The
      presence of mexiletine was confirmed by gas chromatography-mass spectrometry.
      Toxicological analysis revealed the following tissue distribution of mexiletine:
      heart blood, 44.8 micrograms/mL; femoral blood, 10.0 micrograms/mL; vitreous, 8.6
      micrograms/mL; liver, 171.6 micrograms/g; brain, 84.0 micrograms/g; and gastric
      contents, 1464 mg.

PMID- 7823545
TI  - Driving under the influence of GHB?
AB  - A driver was found asleep behind the steering wheel of his car, and the vehicle
      was at rest in a traffic lane with the engine running. His manifestations
      included horizontal and vertical gaze nystagmus, muscle flaccidity, and severe
      ataxia. He admitted ingesting a white powder, which he identified as an amino
      acid, about 1 hour prior to discovery by police. A urine specimen collected
      approximately 1 hour after the traffic stop contained 1975 mg/L of gamma
      hydroxybutyrate (GHB). We tentatively conclude that GHB may cause impairment of
      the psychomotor skills required for safe operation of a motor vehicle.

PMID- 7823546
TI  - Dependence of phonatory effort on hydration level.
AB  - In this study, a double-blind placebo-controlled approach was used to assess the
      relation between hydration level and phonatory effort. Twelve adult, untrained
      voice users with normal voices participated as subjects. Each subject received a
      4-hour hydration treatment, a 4-hour dehydration treatment, and a 4-hour placebo
      (control) treatment. Following each treatment, phonatory effort was measured with
      a physiological measure, phonation threshold pressure (PTP), and with a
      psychological measure, direct magnitude estimation of perceived phonatory effort
      (DMEPPE). Summarizing the results across these measures, the findings indicated
      an inverse relation between phonatory effort and hydration level, but primarily
      for high-pitched phonation tasks. The findings for PTPs replicated those from an
      earlier study conducted without double-blind experimental manipulations
      (Verdolini-Marston, Titze, & Druker, 1990). Theoretical discussion focuses on the
      possible role of vocal fold tissue viscosity for hydration and dehydration
      effects, although direct measures of tissue viscosity are lacking.

PMID- 7823547
TI  - Analysis of vocal disorders with methods from nonlinear dynamics.
AB  - Several authors have recently demonstrated the intimate relationship between
      nonlinear dynamics and observations in vocal fold vibration (Herzel, 1993; Mende,
      Herzel, & Wermke, 1990; Titze, Baken, & Herzel, 1993). The aim of this paper is
      to analyze vocal disorders from a nonlinear dynamics point of view. Basic
      concepts and analysis techniques from nonlinear dynamics are reviewed and related
      to voice. The voices of several patients with vocal disorders are analyzed using
      traditional voice analysis techniques and methods from nonlinear dynamics. The
      two methods are shown to complement each other in many ways. Likely physiological
      mechanisms of the observed nonlinear phenomena are presented, and it is shown how
      much of the terminology in the literature describing rough voice can be unified
      within the framework of nonlinear dynamics.

PMID- 7823548
TI  - Evaluation of a reiterant force-impulse task in the tongue.
AB  - In the current study characteristics of a lingual force-impulse task were
      examined. In the task, neurologically normal adults were required to produce
      sequences of lingual force impulses that were modeled on sequences of syllables
      produced as reiterant speech. The goal of data analysis was to (a) compare the
      timing of the reiterant force sequences to the timing of reiterant speech
      sequences, (b) compare the force magnitudes to expected force variations
      associated with linguistic stress in the reiterant speech sequences, and (c)
      compare the reiterant force magnitudes to maximum lingual forces. Results
      indicated that reiterant force timing is typically slower than reiterant speech
      timing, that reiterant force magnitudes do not vary systematically as a function
      of stress variations in the reiterant speech utterances, and that reiterant force
      magnitudes are typically only a fraction of maximum lingual forces. Results are
      discussed in terms of the relationship between orofacial, nonspeech motor
      performance and speech production performance.

PMID- 7823549
TI  - Human perioral muscle activation patterns.
AB  - Task-dependent human motor organization in the perioral region was examined in
      eight normal adults who performed oral tasks including lip protrusion, chewing,
      and speech. Zero phase-lag correlations among EMG signals recorded from quadrants
      surrounding the lips were calculated in order to determine patterns of motor
      coupling. Results indicated that the perioral musculature is flexible in output
      organization. Activity in all quadrants was highly positively correlated during
      the protrusion task. During the chewing task, correlations were moderate, with a
      stronger pattern bilaterally across the upper and lower lips. The speech tasks
      showed lower levels of correlation among the quadrants, but again the pattern was
      more highly correlated bilaterally than ipsilaterally. Results are compared to
      studies of oral muscle innervation in humans and animals and also are related to
      hypotheses of cortical control patterns for oral movement.

PMID- 7823550
TI  - Pharyngeal effects of bolus volume, viscosity, and temperature in patients with
      dysphagia resulting from neurologic impairment and in normal subjects.
AB  - The oropharyngeal swallow of 10 patients with mild dysphagia at 3 weeks after a
      cerebrovascular accident (stroke), 10 normal subjects, and 8 neurologically
      impaired patients with moderate to severe dysphagia was studied
      videofluorographically to examine the effects of 2 bolus temperatures (room
      temperature and 33 degrees F), 2 volumes, and 2 viscosities on the durations of
      pharyngeal stage swallow events and the frequency and nature of oropharyngeal
      swallowing problems and bolus transit. Normal subjects exhibited significantly
      longer pharyngeal response times and longer laryngeal elevation only for 1 ml
      cold liquid. The stroke patients and the 8 significantly dysphagic neurologically
      impaired patients exhibited very few significant effects of temperature on
      swallowing disorders or swallow measures. Increases in bolus volume and viscosity
      decreased pharyngeal delay times in both neurologically impaired patient groups.
      Stroke patients exhibited significantly longer pharyngeal delay times but shorter
      pharyngeal response times, laryngeal closure, cricopharyngeal opening, and
      laryngeal elevation than normal subjects on some bolus volumes and viscosities.
      Results are discussed in terms of the potentially therapeutic effects of bolus
      volume and viscosity.

PMID- 7823551
TI  - Long-term results of an intensive treatment program for adults and adolescents
      who stutter.
AB  - In order to determine the long-term effects of an intensive treatment program, 17
      adult and 25 adolescent stutterers were tested 2 or 3 times during a 12- to 24
      month post-intensive treatment phase. The results of this study are intended to
      augment and supplement the growing body of evidence about the effects of
      intensive treatment programs on adult and adolescent stutterers. Follow-up
      measures included surprise phone calls to clients at home/work and a self
      administered Speech Performance Questionnaire. Careful training of speech raters
      was undertaken to ensure high reliability of speech measures. Results from the
      phone call samples indicated that about 69% of the subjects maintained a
      satisfactory level of post-treatment fluency, with an additional 7% maintaining a
      level that was judged to be marginally satisfactory. On the self-administered
      Questionnaire, 80% of the subjects rated their speech fluency as good or fair 12
      to 24 months after treatment.

PMID- 7823552
TI  - Intersyllabic movement timing in the fluent speech of stutterers with different
      disfluency levels.
AB  - The goal of this study was to identify possible differences in movement timing in
      the fluent speech of adult stutterers who show varying levels of speech
      disfluency. Strain gauge recordings of lip and jaw movements and
      electroglottographic recordings of laryngeal vibration were obtained in 31
      subjects as they repeated simple speech utterances. Measures of the duration and
      variability of intersyllablic articulatory events were analyzed in relation to
      speech disfluency level and history of speech treatment. As expected, movement
      durations were longer in subjects who had been through speech treatment. No
      significant associations were observed between timing durations and disfluency
      level. However, more disfluent subjects tended to show reduced variability in
      timing durations, an effect that was independent of speech treatment. This
      finding is interpreted in relation to previous observations on control systems
      that show instability and disfunction in association with reduced output
      variability. When disfluency level was measured during physiologic testing,
      duration interacted with speech treatment, with more disfluent subjects in the
      treatment group showing increased durations in their fluent speech. This effect
      is attributed to volitional control intended to facilitate speech fluency.

PMID- 7823553
TI  - Temporal dynamics of repetitions during the early stage of childhood stuttering:
      an acoustic study.
AB  - The purpose of this study was to compare duration characteristics of single
      syllable whole-word repetitions (with one and two repeated units) and part-word
      repetitions (with one repeated unit) in the speech of preschool children who
      stutter (N = 20) recorded near the onset of their stuttering to those of control
      nonstuttering children (N = 20). Disfluent episodes were identified in audiotape
      recordings of the subjects' conversational speech. The digitized signals were
      analyzed by means of the CSpeech computer software (Milenkovic, 1987). Using
      visual displays of sound spectrograms, the durations of the spoken repetition
      unit(s), the silent interval(s) between the units, and the total disfluency were
      measured. The stutters exhibited shorter silent intervals between spoken
      repetition units. The duration of the spoken repetition units was very similar
      for the two groups of children. The total duration of the stutterers'
      disfluencies was significantly shorter because of their shorter silent intervals
      when compared to disfluencies of equal repetition units produced by the control
      subjects. Statistical analysis revealed that silent interval duration was capable
      of differentiating stuttering from normally fluent children with 72-87% accuracy,
      dependent upon the disfluency type. To the degree that the groups of subjects
      represented random samples of the two specified populations from which they were
      drawn, there appears to be an overall tendency for repetitions during the early
      stage of stuttering to be produced at a faster rate than repetitions produced by
      nonstuttering children.

PMID- 7823554
TI  - A structured approach to voice range profile (phonetogram) analysis.
AB  - A new method to analyze voice range profiles (phonetograms) is described. The
      structured analysis is based on quantitatively determining the features: shape,
      area, and "speaking range" dynamics, without distorting the shape of
      phonetograms. The parameter sets describing these features are calculated
      independently of fundamental frequency, which makes it possible to compare
      phonetograms. Two phonetograms representing a normal and a pathological example
      are used to illustrate the proposed method. The process provides a tool for
      establishing normative data for specified groups.

PMID- 7823555
TI  - A measure of the contribution of a gesture to the perception of speech in
      listeners with aphasia.
AB  - The contribution of a visual source of contextual information to speech
      perception was measured in 12 listeners with aphasia. The three experimental
      conditions were: Visual-Only (referential gesture), Auditory-Only (computer
      edited speech), and Audio-Visual. In a two-alternative, forced-choice task,
      subjects indicated which picture had been requested. The stimuli were first
      validated with listeners without brain damage. The listeners with aphasia were
      subgrouped as having high or low language comprehension based on standardized
      test scores. Results showed a significantly larger contribution of gestural
      information to the responses of the lower-comprehension subgroup. The
      contribution of gesture was significantly correlated with the amount of ambiguity
      experienced with the auditory-only information. These results show that as the
      auditory information becomes more ambiguous, individuals with impaired language
      comprehension deficits make greater use of the visual information. The results
      support clinical observations that speech information received without visual
      context is perceived differently than when received with visual context.

PMID- 7823556
TI  - Developmental phonological disorders. I: A clinical profile.
AB  - Detailed information on the speech, language, prosody, and voice characteristics
      of children with developmental phonological disorders is central to diverse
      research questions. The present study provides a clinical profile of 178 children
      with developmental phonological disorders. It includes information from prior
      reports (Shriberg & Kwiatkowski, 1982a; Shriberg, Kwiatkowski, Best, Hengst, &
      Terselic-Weber, 1986) and from several new measures on a sample of 64 children.
      The speech, prosody-voice, and causal-correlates profiles for the most recent
      sample are consistent with prior findings, providing a descriptive profile for
      forthcoming subgroup research and companion studies addressing short-term
      (Shriberg, Kwiatkowski, & Gruber, 1994) and long-term (Shriberg, Gruber, &
      Kwiatkowski, 1994) speech-sound normalization.

PMID- 7823557
TI  - Developmental phonological disorders. II. Short-term speech-sound normalization.
AB  - A companion paper (Shriberg & Kwiatkowski, 1994) provides a descriptive profile
      of three samples of children (n = 178) with developmental phonological disorders.
      The present paper describes a conceptual framework for short-term and long-term
      speech-sound normalization research and reports 1-year normalization outcomes for
      54 of the children described in the companion paper. Although certain individual
      speech variables were significantly associated with normalization, there were no
      speech, prosody-voice, or risk-factor variables that discriminated children who
      achieved short-term speech-sound normalization in 1 year. Findings are discussed
      in relation to a two-factor framework to study and predict speech-sound
      normalization in developmental phonological disorders (Kwiatkowski & Shriberg,
      1993; Shriberg, Kwiatkowski, & Gruber, 1992).

PMID- 7823558
TI  - Developmental phonological disorders. III: Long-term speech-sound normalization.
AB  - Prior articles in this series provide a descriptive profile of 178 children with
      developmental phonological disorders (Shriberg & Kwiatkowski, 1994) and
      predictive correlates of short-term speech-sound normalization in 54 children
      (Shriberg, Kwiatkowski, & Gruber, 1994). The present article reports findings
      from a study of 10 children with developmental phonological disorders whose
      progress was followed at least once yearly for 7 years. Analyses characterize the
      sequence, rates, and error patterns of long-term speech-sound normalization in
      relation to developmental perspectives on the nature of children's phonological
      disorders. Findings are interpreted to support the hypothesis of a critical
      period for speech-sound development, with long-term normalization of significant
      speech delay reaching a chronological age boundary at approximately 8.5 years.

PMID- 7823560
TI  - Grammatical morpheme acquisition: do norms exist?

PMID- 7823559
TI  - Correlates of directiveness in the interactions of fathers and mothers of
      children with developmental delays.
AB  - Twenty preschool-age children with developmental delays and language impairment
      participated in this study, which compared fathers' and mothers' directiveness
      and parental stress. Similarities between fathers and mothers were found for
      turntaking control, response referents, and responses to the child's
      participation. However, fathers differed from mothers in two of the dimensions of
      directiveness examined: fathers used more response control and topic control than
      mothers. Both parents reported similarly low levels of child-related and
      parenting stress, but mothers perceived more stress than fathers related to the
      responsibilities associated with parenting a child with a handicap. Correlations
      between directiveness, child characteristics, and stress revealed that fathers
      used greater turntaking control and topic control with children who were
      developmentally less mature, whereas mothers used greater topic control with
      children who were less involved in interaction. Both fathers' and mothers' use of
      response control was positively related to stress. Implications for involving
      fathers in parent-focused intervention include screening father-child
      interactions before intervention, interpreting parent-child interaction styles in
      terms of their role in enhancing the child's social participation, and
      acknowledging the role of familial factors (such as stress) on interaction
      styles.

PMID- 7823561
TI  - Effects of phonetic context on audio-visual intelligibility of French.
AB  - Bimodal perception leads to better speech understanding than auditory perception
      alone. We evaluated the overall benefit of lip-reading on natural utterances of
      French produced by a single speaker. Eighteen French subjects with good audition
      and vision were administered a closed set identification test of VCVCV nonsense
      words consisting of three vowels [i, a, y] and six consonants [b, v, z, 3, R, l].
      Stimuli were presented under both auditory and audio-visual conditions with white
      noise added at various signal-to-noise ratios. Identification scores were higher
      in the bimodal condition than in the auditory-alone condition, especially in
      situations where acoustic information was reduced. The auditory and audio-visual
      intelligibility of the three vowels [i, a, y] averaged over the six consonantal
      contexts was evaluated as well. Two different hierarchies of intelligibility were
      found. Auditorily, [a] was most intelligible, followed by [i] and then by [y];
      whereas visually [y] was most intelligible, followed by [a] and [i]. We also
      quantified the contextual effects of the three vowels on the auditory and audio
      visual intelligibility of the consonants. Both the auditory and the audio-visual
      intelligibility of surrounding consonants was highest in the [a] context,
      followed by the [i] context and lastly the [y] context.

PMID- 7823562
TI  - Effect of video frame rate on subjects' ability to shadow one of two competing
      verbal passages.
AB  - In a study addressing future use of video-telephone systems, the ability of 52
      young adults with normal hearing to shadow verbal passages was assessed when they
      could both hear and observe the speaker. This performance was compared to
      performance in an audio-alone condition. The passages were presented against an
      irrelevant background message. Effects of varying the video frame rate (i.e., the
      rate at which frames were sampled) were examined, using rates of 8.3, 12.5, 16.7,
      and 25 Hz. The presence of the visual image of the relevant speaker always
      improved performance when compared with a baseline audio-alone condition. The
      motion of the speaker's face may generally support the focusing of attention on
      the target message. However, effects of video frame rate were also apparent,
      suggesting that specific visual cues became available as the temporal resolution
      improved. When frame rates of 8.3 Hz and the maximum available rate of 25 Hz were
      compared, shadowing performance was significantly better across the subject group
      at the higher frame rate. The comparison of frame rates of 12.5 and 25 Hz did not
      show reliably improved performance across the whole subject group at 25 Hz,
      although a small number of subjects seemed to benefit. This suggests there may be
      some differences in the visual cues used by subjects and consequent differences
      in the way individuals perform under different frame rates. Performance at 16.7
      and 25 Hz did not differ, and this is consistent with previous research that
      tested people with hearing loss.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7823563
TI  - Test-retest reliability of the profile of hearing aid performance.
AB  - This study was designed to replicate the test-retest reliability and critical
      difference components of the Profile of Hearing Aid Performance (PHAP) as
      established by Cox and Gilmore (1990). Subjects were 18 experienced hearing aid
      users ranging in age from 62 to 74 years old. The initial and retest
      administrations of the PHAP were conducted with no rehabilitative treatment
      pertaining to hearing loss or amplification provided during the intervening
      period. The interval between the first and second administrations of the profile
      was 4-5 months. The mean test-retest difference scores obtained in this
      investigation were small, not unlike those reported by Cox and Gilmore (1990).
      Critical difference (CD) values closely approximated those of the previous study
      except for the Background Noise subscale and the Environment C scale. A pooled
      estimate of each standard deviation of test-retest differences was computed using
      data from both investigations. This resulted in critical differences considered
      to be more precise than the CD values derived from either study alone. Findings
      strongly support the utility of the PHAP as an effective tool for generating
      reliable information regarding self-perceived hearing aid performance.

PMID- 7823564
TI  - Mechanisms of recovery of swallow after supraglottic laryngectomy.
AB  - This study examines oropharyngeal swallow disorders and measures of pharyngeal
      and laryngeal movement during deglutition from videofluorographic studies of
      oropharyngeal swallow in 9 patients who had undergone supraglottic laryngectomy
      and 9 age-matched normal subjects. The swallows of surgical patients were
      examined at 2 weeks and 3 months postoperatively. Two critical factors in
      recovery of swallowing were identified: (a) airway closure at the laryngeal
      entrance, that is, the space between the arytenoid cartilage and the base of the
      tongue, and (b) the movement of the tongue base to make complete contact with the
      posterior pharyngeal wall. When patients achieved these two functions, they
      returned to normal swallowing. The duration of tongue base contact to the
      posterior pharyngeal wall and extent of anterior movement of the arytenoid
      increased significantly from 2 weeks to 3 months in the surgical patients. At 2
      weeks postsurgery, patients who had undergone supraglottic laryngectomy exhibited
      significantly shorter airway closure and tongue base to pharyngeal wall contact,
      reduced laryngeal elevation, increased width of cricopharyngeal (CP) opening, and
      later onset of airway closure and tongue base movement than normal subjects.
      These significant differences remained at 3 months postoperatively, although
      swallow measures were moving toward normal in the patients who had undergone
      supraglottic laryngectomy. Comparison of patients not eating at 2 weeks with
      patients at the time of first eating revealed significantly longer duration of
      tongue base contact to the pharyngeal wall, longer duration of airway closure,
      and greater movement of the arytenoid in patients who were eating. Results
      indicate that the focus of swallowing therapy after supraglottic laryngectomy
      should be on improvement of posterior movement of the tongue base and anterior
      tilting of the arytenoid to close the airway entrance and improve bolus
      propulsion (in the case of the tongue base).

PMID- 7823565
TI  - Motor unit territories in the human perioral musculature.
AB  - The perioral region was divided into four quadrants, and electromyograms (EMGs)
      were recorded from each area. The coherence function (i.e., the squared cross
      correlation between two signals computed at each frequency in the spectrum) was
      used to determine aspects of the organization of motor unit territories and to
      examine potential higher level sources of input in speech and nonspeech tasks.
      Coherence functions were computed between pairs of EMGs and were examined for
      significant values in the range of 20-240 Hz. When two pairs of electrodes were
      intentionally placed to record the activity from a common subset of motor units
      in a single quadrant of the lower lip, all subjects exhibited significant broad
      band coherence in every frequency in all experimental tasks. Thus, the presence
      of such a pattern of broad-band significant coherence for EMG pairs recorded from
      different quadrants would indicate that single motor unit territories extended
      across perioral quadrants. When separate EMG recordings were obtained from the
      four quadrants of the lips, coherence functions computed between EMG pairs were
      typically zero across the entire frequency range. These findings suggest that
      perioral motor unit territories are organized into nonoverlapping quadrants.
      Further, the present analyses suggest that, unlike bilateral pairs of jaw-closing
      muscles during chewing, these motor units are not driven by any correlated
      oscillatory activity in chewing or other oral motor tasks.

PMID- 7823566
TI  - Consistency and reliability of voice quality ratings for different types of
      speech fragments.
AB  - This study describes a perception experiment in which listeners were asked to
      rate voice fragments obtained from a variety of speakers on grade, breathiness,
      and roughness. Four different types of stimuli were presented to each listener.
      One type of stimulus was based on connected speech fragments; the other three
      were based on different segments of a sustained vowel, yielding a 200 msec vowel
      onset stimulus, a 200 msec post-onset stimulus, and a 1000 msec whole vowel
      stimulus. Analyses focused on the consistency and reliability of grade,
      roughness, and breathiness ratings. Results indicated that stimulus type had
      virtually no effect on either within- or between-listener consistency of the
      grade, breathiness, or roughness ratings. Rating reliability too was hardly
      influenced by stimulus type. When determined as a function of the overall degree
      of deviance of a voice, the reliability of breathiness and roughness ratings was
      slightly higher for whole vowel and vowel onset stimuli than for connected speech
      and post-onset stimuli. It is concluded that connected speech stimuli are not
      necessarily to be preferred over vowel-type stimuli for a perceptual evaluation
      of grade, roughness, or breathiness. The somewhat higher reliability of ratings
      on vowel onset and whole vowel stimuli as compared to the post-onset stimuli is
      taken as an indication that the onset part of a vowel may contain voice quality
      cues that are less salient in the most stable part of a vowel.

PMID- 7823567
TI  - A decade of training in surgical oncology.

PMID- 7823568
TI  - Liver metastases from soft tissue sarcomas.
AB  - Twenty-three patients with liver metastases from soft tissue sarcoma were
      reviewed. Patients with metastases to the liver first had poorer survival than
      those who developed spread to other sites first (P = .0035). The median time from
      diagnosis of the primary tumor to diagnosis of liver metastases was 14 months;
      the median time from diagnosis of liver metastases to death was 7 months. The
      median survival from diagnosis for four patients who underwent liver resection
      was 54 months compared to 20 months for those who did not undergo resection (NS).
      Soft tissue sarcomas rarely metastasize to the liver; when this occurs it is
      usually late in the course of the disease and after it has spread to other sites.
      The opportunity for successful liver resection is infrequent but may prolong
      survival.

PMID- 7823569
TI  - Establishment and characterization of TSGH9201, a human gastric carcinoma cell
      line that is growth inhibited by epidermal growth factor.
AB  - A human signet ring gastric carcinoma cell line TSGH9201 was established in
      vitro. The cells grew in vitro as a monolayer with polygonal morphology and had a
      population doubling time of 34 hours. The cells secreted tumor markers CEA and CA
      125. They were, however, not tumorigenic in athymic nude mice. Karyotypic
      analysis demonstrated a near tetraploidy with a modal chromosome number of 98.
      Northern blotting and immunocytochemical analysis revealed the expression of both
      transforming growth factor alpha and high levels of epidermal growth factor
      receptor. Cell growth was inhibited by the epidermal growth factor in vitro. The
      cell line may be a useful tool to study autocrine growth regulation through the
      epidermal growth factor receptor.

PMID- 7823571
TI  - Postoperative radiotherapy in gastric cancer.
AB  - Surgeons in Poland are very skeptical about the positive role of adjuvant
      irradiation in patients with gastric cancer. A retrospective study of 21 patients
      with operable gastric cancer referred for irradiation to Cancer Centre in Warsaw
      between December 1984 and December 1991 was performed. Patients were qualified to
      receive adjuvant treatment because of bad prognostic factors--nonradical surgery
      (10 patients), infiltration of entire thickness of gastric wall (13 patients),
      and metastases in regional lymph nodes (9 patients). All patients were in good
      condition. They were treated by either telecobalt 60 unit or linear accelerator
      using 9-15 MeV photons. The total dose to the gastric bed and lymphatic was 46-50
      Gy in 25 to 28 fractions, 5 days a week. The tolerance of treatment was good.
      None of these patients received 5-FU either during irradiation or as maintenance
      therapy. We have obtained more than 50% overall survival rate at 3 years. Median
      survival was 27 months and median recurrent-free interval 27 months. Local
      recurrence was found in four patients, distant metastases in five patients. In
      the group of 10 patients with nonradical surgery, 5 are alive without evidence of
      disease from 2 up to 7 years after treatment. Our preliminary results and good
      tolerance of treatment seem to support the beneficial role of adjuvant
      radiotherapy after gastrectomy in patients with risk factors of locoregional
      cancer recurrence.

PMID- 7823570
TI  - Rapid and accurate method for delineating cancer lesions in laparoscopic
      colectomy using activated carbon injection.
AB  - The aim of our study was to evaluate the clinical efficacy of preoperative
      injection of activated carbon in delineation of cancer location in laparoscopic
      colectomy. Activated carbon particles were injected during endoscopy into the
      normal colonic wall surrounding cancer lesions in five cases of early colon
      cancer, prior to laparoscopic surgery. The carbon-stained area was clearly
      recognizable as a blackened patch on the serosal surface of the colon. Using the
      carbon-stained area as a reference point, partial colectomies were successfully
      performed on all five patients. The preoperative injection of activated carbon
      assisted in the intraoperative delineation of early colonic cancer lesions. This
      method is recommended for the rapid and accurate delineation of early colonic
      cancers in laparoscopic surgery.

PMID- 7823572
TI  - Lymphokine-activated killer cell function of lymphocytes from regional lymph
      nodes in patients with gastric carcinoma.
AB  - Lymphokine-activated killer (LAK) cells generated by culture of regional lymph
      node cells (LNC) with interleukin 2 (IL 2) for 4 and 11 days were examined for
      their functional capabilities in comparison with those of peripheral blood
      mononuclear cells (PBM) in 25 patients with gastric carcinoma. The cytotoxic
      activity of LAK cells induced from LNC for 4-day culture with IL 2 was
      significantly lower than that from PBM. However, the LNC-LAK cytotoxicity was
      markedly increased up to almost the same level as that of PBM after 11-day
      culture. The production of interferon-gamma (INF-gamma) and tumor necrosis factor
      alpha (TNF-alpha) from nonadherent LAK cells in LNC was also significantly
      reduced as compared to that from PBM 4 days after culture, when stimulated with
      or without tumor target, Raji cells. After 11-day culture with IL 2, however, the
      levels of these cytokines produced by LNC-LAK cells either with or without
      stimulation by tumor target were comparable to those by PBM-LAK cells, although
      the release of these cytokines was markedly reduced when compared to that after 4
      day culture. Phenotypic analysis revealed decreased proportion of cells mediating
      NK activity in LNC before and 4 days after culture. CD56+ and CD57+ cells in LNC
      were increased after 11-day culture, although the percentages of these cells were
      still low as compared to those in PBM. The proportions of OKIa1+ and CD25+ cells
      were uniformly increased after 4 and 11-day culture in both cell populations.
      Changes in subpopulations of CD4+ and CD8+ cells in LNC were not apparently
      different from PBM. These results indicated the differential LAK cell function of
      cells from regional lymph nodes from PBM in patients with gastric carcinoma.

PMID- 7823573
TI  - Clinicopathological study of primary malignant tumors of the lung: an analysis of
      993 tumors resected at the Kanazawa University Hospital between 1979-1993.
AB  - A retrospective study was conducted of 993 malignant tumors of the lung in 977
      patients. The male-female sex ratio was 2.6:1. The age distribution of the males
      did not differ from that of the females and the overall mean age was 64.3 +/- 9.5
      years (range, 13-85 years). Forty-three percent of the patients were in their
      seventh decade. The location was peripheral in 81% of the tumors and central in
      19%. Of the central tumors, 85% were squamous cell (epidermoid) carcinoma (SCC),
      while 58% of the peripheral tumors were adenocarcinoma (ADENO). In males, 49% of
      all tumors were SCC and 36% ADENO, while in females 76% were ADENO. The incidence
      of positive lymph node metastasis increased in parallel with the pT status in
      both central and peripheral carcinomas. However, it was noted that, of peripheral
      lung carcinomas, no SCC with a diameter of 15 mm or less had lymph node
      metastasis, whereas 18.9% of the ADENO of this size were positive for lymph node
      metastasis. These results indicate that lymph node metastasis can occur even in
      small-sized peripheral ADENO less than 15 mm. Thus, early detection and surgery
      together with mediastinal lymph node dissection are necessary even for small
      sized tumors to improve the prognosis in patients with peripheral ADENO of the
      lung.

PMID- 7823574
TI  - Concurrent chemotherapy (5-fluorouracil and cisplatin) and radiation therapy for
      inoperable squamous cell carcinoma of the esophagus potentially followed by
      surgery.
AB  - Twenty-four previously untreated patients with primary inoperable squamous cell
      carcinoma of the esophagus showing no evidence of hematogenous metastasis were
      treated with concurrent chemotherapy and radiation therapy (CRT) followed by
      surgical resection if possible. The chemotherapy regimen consisted of 5
      fluorouracil 750 mg/m2 on days 1-4 and 21-24, and cisplatin 70 mg/m2 on days 1
      and 21. Radiation therapy was administered over days 1-26 (200 cGy/day five times
      per week with an initial planned dose of 40 Gy). Five patients (8%) showed
      complete response (CR), 14 patients (58%) had partial response (PR), and 19 had
      good local control (CR 2, PR 17). Eleven cases (48%) underwent esophageal
      resection with no operative mortality. Curative resection was accomplished in
      eight cases (35%). Toxicities observed in CRT were leukopenia (grades 3 and 4)
      38%, nausea and vomiting (grades 2 and 3) 67%, esophagitis 42%, and fever 42%.
      The median survival time (MST) for 11 neoadjuvant cases was 349 days (P < 0.05)
      compared to 212 days for palliative treatment (six cases) and 126 days for no
      treatment (six cases) after CRT. The MST of eight patients who received curative
      resection had not been reached after a 17-month median follow-up time. Concurrent
      chemotherapy with 5-fluorouracil plus cisplatin and radiation proved to be a safe
      regimen yielding a satisfactory response and minimal toxicity in this particular
      group of patients. Extensive surgery was thus determined to be feasible after CRT
      and to contribute to prolonging survival.

PMID- 7823575
TI  - Results of surgical treatment of pulmonary metastases.
AB  - From 1970 to 1993, 155 thoracotomies for metastatic lung tumors were performed on
      113 patients in the Department of Surgery, Kanazawa University School of
      Medicine. Overall 30-day mortality amounted to 0.9% (1/113). The cumulative 3-
      and 5-year survival rates were 39.4% and 29.1%, respectively. The overall median
      survival was 24 months. The 5-year survival rate for carcinoma was 37.2% and for
      sarcoma it was 14.5% (P < 0.01). The other significant predictors of better long
      term survival with metastatic lung tumors were solitary lesions, disease-free
      interval (DFI) > 24 months, and tumor size < or = 20 mm in diameter. There was no
      significant difference in survival based on the method of pulmonary resection.
      Repeat thoracotomy for recurrent metastases was performed in 27 patients, whose 5
      year survival rate after the first lung resection was 35.5%. For bilateral
      pulmonary metastases, we recently performed simultaneous bilateral thoracotomy
      via median sternotomy on 25 patients and transsternal simultaneous bilateral
      thoracotomy on 8 patients. The latter procedure provides a wide operative field
      and better survival. We conclude that resection of metastatic lung tumors is safe
      and effective, and that repeat thoracotomy is warranted in selected patients with
      recurrent pulmonary metastases.

PMID- 7823577
TI  - Duodenal leiomyosarcoma.
AB  - Two cases of duodenal leiomyosarcoma were encountered, both of which appeared
      benign by gross and histologic criteria. Both patients suffered recurrences with
      poor outcomes. We reviewed the literature and found four other such cases and
      examined the outcomes in the world literature with respect to tumor size and
      extent of surgical resection. Large size, limited resections, and local
      recurrence were associated with poor outcomes. A 6% rate of lymphatic metastases
      was found, and the bearing this has on the extent of resection is discussed.

PMID- 7823576
TI  - Clinical significance of multidrug resistance and P-glycoprotein expression in
      patients with gastric carcinoma.
AB  - Twenty-four fresh tumors of gastric carcinoma were assessed by flow cytometric
      detection of P-glycoprotein (P-gp) using monoclonal antibody C219. Eight patients
      were P-gp positive. Differentiated gastric carcinomas contained significantly
      higher concentrations of P-gp positive. Incidence of P-gp positive was high in
      advanced stage. In 16 cases estimated chemosensitivity was test assessed by
      thymidine incorporation assay (TIA). Seven of nine multidrug-resistant cases
      according to TIA were P-gp positive and all of seven nonmultidrug resistant cases
      were P-gp negative. Expression of P-gp and multidrug resistance were closely
      correlated (P < 0.01). Also, in 89 patients with operable gastric carcinoma, the
      relation between in vitro chemosensitivity test (TIA) and their clinicopathologic
      features as well as their survival lengths were studied. Thirty-one of 89
      specimens from gastric carcinoma patients were multidrug resistant according to
      TIA. Patients in the multidrug-resistant group had a significantly poorer
      cumulative survival rate than those who were not multidrug resistant (P < .05).
      The multivariate analysis showed that multidrug resistance is a useful indicator
      of prognosis (P < 0.1). We suggest that multidrug-resistant cases or P-gp
      positive cases of gastric carcinoma are highly malignant, and these
      determinations are clinically useful.

PMID- 7823578
TI  - Ukrainian wrap reconstruction after total gastrectomy minimizes anastomotic
      failure.

PMID- 7823579
TI  - Surrogate endpoint biomarkers for phase II cancer chemoprevention trials.
AB  - Three critical aspects govern successful Phase II cancer chemoprevention trials-
      well-characterized agents, suitable cohorts, and reliable intermediate biomarkers
      for measuring efficacy. Requirements for the agent are experimental or
      epidemiological data showing chemopreventive efficacy, safety on chronic
      administration, and a mechanistic rationale for the chemopreventive activity
      observed. The cohort should be suitable for measuring the chemopreventive
      activity of the agent and the intermediate biomarkers chosen. Also, many cohorts
      proposed for Phase II trials are patients with previous cancers or premalignant
      lesions. For such patients, the trials should be conducted within the context of
      standard treatment to avoid unusual risks. The criteria for biomarkers are that
      they fit expected biological mechanisms (i.e., differential expression in normal
      and high-risk tissue, on or closely linked to the causal pathway for the cancer,
      modulated by chemopreventive agents, and short latency compared with cancer), may
      be assayed reliably and quantitatively, measured easily, and correlate to
      decreased cancer incidence. They must occur in sufficient incidence to allow
      their biological and statistical evaluation relevant to cancer. Since
      carcinogenesis is a multipath process, single biomarkers are difficult to
      validate as surrogate endpoints, as they may appear on only one or a few of the
      many possible causal pathways. Panels of biomarkers, particularly those
      representing the range of carcinogenesis pathways, may prove more useful as
      surrogate endpoints. It is important to avoid relying solely on biomarkers
      representing isolated events that may or may not be on the causal pathway or
      otherwise associated with carcinogenesis. These include markers of normal
      cellular processes that may be increased or expressed during carcinogenesis, but
      are nonspecific.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7823580
TI  - Development of surrogate endpoint biomarkers for clinical trials of cancer
      chemopreventive agents: relationships to fundamental properties of preinvasive
      (intraepithelial) neoplasia.
AB  - The tissue changes offering the greatest immediate potential for development as
      surrogate endpoint biomarkers (SEBs) to be used in Phase II trials of cancer
      chemopreventive agents are those derived from the microscopic tissue changes
      pathologists use to make the diagnosis of preinvasive (intraepithelial)
      neoplasia. These changes comprise four categories: proliferative index, ploidy,
      nuclear morphometry (size, shape, texture, and pleomorphism), and nucleolar
      morphometry (number, size, shape, position, and pleomorphism). Computer-assisted
      image analysis (CIA) permits dozens of additional morphometric parameters to be
      developed. Other categories of candidate SEBs are: DNA and chromosomal structural
      changes associated with genomic instability, activation of oncogenes and
      inactivation of tumor suppressor genes, structural changes in differentiated
      molecules, and aberrations of growth factor/receptor structure and function. Self
      perpetuating DNA breakage with secondary mutator mutations in genomic stability
      genes is a major mechanism by which the genomic instability characteristic of
      neoplasia occurs, and from which stem other basic neoplastic properties,
      including clonal evolution, along multiple pathways of genetic variation that are
      stochastically determined, continuously increasing proliferation, rate and extent
      of phenotypic heterogeneity. SEBs resulting from genomic instability include
      homogeneously staining regions, double minute chromosomes, micronuclei,
      dicentrics, gene amplification, loss of heterozygosity, and alterations in
      chromosome number. Newly developed assays for detecting genomic instability
      include comparative genomic hybridization using fluorescence in situ
      hybridization on > 20 micron-thick sections monitored by confocal laser scanning
      microscopy, assays for microsatellite instability, and restriction landmark
      genomic scanning. These assays offer promise for detecting the earliest molecular
      changes of neoplasia in normal-appearing epithelium prior to the onset of the
      dysplastic phase of intraepithelial neoplasia.

PMID- 7823581
TI  - Quality control considerations for Ki-67 detection and quantitation in paraffin
      embedded tissue.
AB  - Proliferative activity has prognostic significance in many solid tumors.
      Immunohistochemical analysis of tumor proliferation may be accomplished with the
      Ki-67 monoclonal antibody which recognizes a nuclear antigen expressed throughout
      the cell cycle. This antibody, however, cannot be used with formalin-fixed,
      paraffin-embedded tissue. Recently, a Ki-67 equivalent murine monoclonal antibody
      (MIB-a; AMAC, Inc., Westbrook, ME) was generated which can detect tumor
      proliferative activity in routinely processed tissue with microwave oven heating.
      Using quantiative image analysis, we assessed the effect of delay in fixation,
      total time of formalin fixation, and microwave heating time on the
      immunoreactivity of this antibody. The effect of time to fixation (0, 2, 4, 8, or
      24 hours) on MIB-1 immunostaining was determined in various tumor tissues using
      image analysis. No significant difference in positive nuclear area was observed
      for tissues in which fixation was delayed for as long as 8 hours relative to
      controls. A 24-hour fixation delay resulted in a small decrease in positive
      nuclear area was observed for tissues in which fixation was delayed for as long
      as 8 hours relative to controls. A 24-hour fixation delay resulted in a small
      decrease in positive nuclear area relative to controls. The effect of fixation
      time (4, 24, or 48 hours) and microwave oven heating time on MIB-1 immunostaining
      was studied in tonsil tissue, and quantitated by image analysis. Good MIB-1
      immunostaining was observed for all microwave oven heating times in tissue fixed
      for 4 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7823582
TI  - In vivo fluorescence spectroscopy: potential for non-invasive, automated
      diagnosis of cervical intraepithelial neoplasia and use as a surrogate endpoint
      biomarker.
AB  - A quantitative measure of intraepithelial neoplasia which can be made in vivo
      without the need for tissue removal would be of clinical significance. Our group
      is working to develop such a technique based on fluorescence spectroscopy. This
      paper reviews the use of fluorescence spectroscopy for tissue diagnosis,
      describes our work to apply this technique to the diagnosis of cervical
      intraepithelial neoplasia (CIN), and discusses the potential utility of
      fluorescence spectroscopy as a surrogate endpoint biomarker (SEB). The
      development and performance of a spectroscopic diagnostic algorithm for CIN is
      described in detail. Fluorescence excitation-emission matrices (EEMs) were
      obtained in vitro for 18 cervical biopsies from 10 patients. At all excitation
      emission maxima, but especially at 330 nm excitation, 385 nm emission, the
      average normalized fluorescence intensity of histologically normal tissue is
      greater than that of histologically abnormal tissue. A diagnostic algorithm based
      on the relative intensity at 330 nm excitation, 385 nm emission can differentiate
      histologically normal and abnormal biopsies with a higher sensitivity, but a
      lower positive predictive value and specificity than colposcopy. However, paired
      comparison of histologically normal and abnormal biopsies from the same patient
      results in a sensitivity of 75%, positive predictive value of 86%, and
      specificity of 88% for spectroscopic identification of histological abnormality-
      similar to that of colposcopy. Based on these results, in vivo studies of
      cervical tissue fluorescence were conducted. A spectroscopic system incorporating
      a pulsed nitrogen laser, an optical fiber probe, and an optical multi-channel
      analyzer was used to record fluorescence spectra of the intact cervix at
      colposcopy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7823583
TI  - Quantitation and morphometric analysis of tumors by image analysis.
AB  - Digital image analysis provides objective measurements of tissue and cell
      analytes previously interpreted subjectively. Both analyte concentration
      determination and morphometric analyses are possible. Calibration of the
      instrument and the use of standards and controls are essential for precise and
      reproducible quantitation of the analyte. Multi-tissue blocks ensure reproducible
      staining of the batch in quantitative immunohistochemical assays such as breast
      cancer estrogen and progesterone receptors. These multi-tissue blocks can be
      shared among laboratories to reduce interlaboratory variation and to objectively
      quantitate estrogen and progesterone receptors in clinical trials. In colon
      carcinoma, p53 can be quantitated objectively by image analysis. In prostate
      carcinoma, morphometric analysis of nuclear shape, nuclear roundness factor, and
      variations in nuclear size are objective measurements which constitute the
      pathologist's nuclear grade. Developments in instrumentation have now made it
      possible to combine analyte determination (such as DNA ploidy) and morphologic
      analysis of tumors, a diagnostic improvement over either method alone. A study
      employing image analysis to detect and quantitate androgen receptors and p53 in
      formalin-fixed, paraffin-embedded prostate cancer biopsies is underway to
      determine the utility of androgen receptors in predicting response to hormonal
      therapy. Histopathological features such as nuclear size, shape, and pleomorphism
      must be converted to image features such as area, shape factor, and variance of
      the area; this feature vector must be correlated with the pathologist's expert
      opinion or diagnosis. Other applications of image analysis include quantitation
      of immunofluorescent assays such as anti-nuclear antigen or anti-cytoplasmic
      nuclear antigen. Fluorescent image analysis provides more precision and greater
      reproducibility, as well as reduced test costs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7823584
TI  - Immunohistochemical detection of sex steroid receptors in breast cancer using
      routine paraffin sections: comparison with frozen sections and enzyme
      immunoassay.
AB  - Estrogen and progesterone receptors (ER and PR) on 48 surgically removed breast
      cancers were evaluated by three methods: immunoenzymatic (ER/PR-EIA),
      immunohistochemical in frozen sections (ER/PR-ICA), and immunohistochemical in
      paraffin sections (ER/PR-PAR). The monoclonal antibodies H222 and KD68 were used
      for immunohistochemical detection of ER and PR, respectively. Immunohistochemical
      stains for pS2, an estrogen-regulated protein, were also done for compatibility
      with previous ER/PR-PAR studies. We assessed concordance with chi-square and
      Pearson's correlation coefficient. We concluded that ER/PR-PAR is the least
      sensitive of the three assays (90.9% ER, 88.5% PR) and, until appropriate
      technical and clinical validation is achieved, should not be used as a first-line
      assay. Also, because of this lower sensitivity, we recommended that pS2
      evaluation always accompany ER/PR-PAR to facilitate distinction between clinical
      negatives and those due to irretrievably lost immunoreactivity. We also conclude
      that ER/PR-ICA is a good semi-quantitative method that, in combination with ER/PR
      EIA, most accurately assesses receptor status.

PMID- 7823585
TI  - Estrogen receptor immunocytochemistry: the promise and the perils.
AB  - Estrogen receptor immunocytochemistry (ERICA) is favored over dextran-coated
      charcoal (DCC) or sucrose gradient assay (SGA) by many pathologists and
      oncologists since it allows an estimation of tumor cell and tissue heterogeneity
      and permits assays to be performed on specimens not suitable for DCC/SGA.
      Additionally, ERICA can be performed with greater ease and with less expense at
      the level of the community hospital pathology laboratory. Initially, like
      DCC/SGA, ERICA had to be done on fresh or frozen tumor samples or face a
      significant loss in sensitivity when applied to formalin-fixed, paraffin-embedded
      sections. Recently, several anti-estrogen receptor (ER) antibodies have appeared
      which can be successfully employed to assay routinely prepared tissue sections if
      used in conjunction with new antigen-retrieval techniques such as the microwave
      oven and citrate buffers. However, more work is needed to correlate results of
      these new procedures with biochemical ER assays, endocrine response, and survival
      before they can be reliably employed as prognostic parameters. Furthermore, if
      any ER assay is to be useful and valid, strict attention must be paid to details
      of specimen collection, freezing, and fixation in order to inhibit receptor
      degradation and false negative results.

PMID- 7823586
TI  - Quantitative immunohistochemical assay for hormonal receptors: technical aspects
      and biological significance.
AB  - Over 250 breast carcinomas were studied in order to establish whether or not
      quantitative immunohistochemical assays (ICA) for estrogen and progesterone
      receptors (ER and PR) with computer-assisted image analysis could favorably
      compare with standard cytosolic assays. Initially, variable antigenic
      preservation secondary to improper tissue fixation and processing led to
      irregular receptor preservation and unevenly stained areas indistinguishable from
      true intratumor antigenic heterogeneity. As a direct consequence of the field
      selections chosen for analysis, assay reproducibility was less than optimal.
      Proper tissue fixation and handling eliminated most of the irregular staining;
      selection of fields to analyze became less cumbersome and more reproducible.
      Differences in staining intensity due to minimal variations in the ICA also
      resulted in difficult reproducibility. Standardizing the technique and using an
      automatic stainer notably eliminated that problem. The second and equally
      important question was to establish if quantitative ER-ICA had relevance as a
      predictor for prognosis. The Kaplan-Meier product limit estimator for quantitated
      ER values and Cox regression for risk of mortality and disease progression were
      performed. The results obtained discriminated high- and low-risk groups for
      overall survival (p = 0.016) better than the dextran-coated charcoal assay.
      Elimination of two major obstacles and proof of the predictive value of
      quantitative ICA has transformed the assay into a valid alternative to cytosolic
      methods; however, before that takes place it is critical to establish standard
      procedures for both ICA and quantitation so interlaboratory variability is
      reduced to a minimum.

PMID- 7823587
TI  - Quality control in image cytometry: DNA ploidy.
AB  - DNA ploidy has become a commonly performed quantitative image cytometry test in
      microscopic pathology. This has led to the need to develop quality control
      procedures to aid in assuring uniform and reliable test results. There are a
      number of unique issues related to the emerging technology of image analysis and
      its routine use as a quantitative microscopic assay that require consideration
      before establishing a quality control program. Previous considerations of this
      topic have primarily related to measurement issues, e.g., accuracy comparisons to
      other methodologies, calibration of instrumentation, sources of measurement
      error, and the interpretation of measurements results. Although these issues are
      critically important, with more routine usage the focus is now turning to quality
      control of the overall testing process in everyday use. Control charts and
      methods of controlling the total measurement process such as have been used in
      clinical chemistry, need to be established. As one of the first image assays in
      pathology, quality control procedures established now for DNA ploidy measurements
      could help shape the development of this field, especially as pathology
      transitions from being a subjective visual microscopic inspection process to a
      quantitative measurement process. This paper discusses these issues as they
      relate to overall quality assurance for the DNA ploidy test and describes a
      quality control program developed for an active breast cancer testing laboratory
      specializing in image cytometry tests, including DNA ploidy. The quality control
      program includes calibration control charts, control charts for internal diploid
      controls, check samples, and computerized individual histogram interpretation.

PMID- 7823588
TI  - Cell proliferation in hyperplastic and in situ carcinoma lesions of the breast
      estimated by in vivo labeling with bromodeoxyuridine.
AB  - The proliferative activity of normal, benign proliferative, and carcinoma in situ
      (CIS) breast lesions was studied by in vivo labeling with 5-bromodeoxyuridine
      (BrdU) in 35 patients with concurrent breast carcinoma. The BrdU-labeled cells
      were identified on histologic sections by an anti-BrdU monoclonal antibody and an
      immunoperoxidase reaction. The percentage of BrdU-labeled cells in nonatypical
      hyperplasia (NAH) was higher (1.15 +/- 1.14%) than normal epithelial cells (0.67
      +/- 0.56%, p = 0.066, borderline significance). This difference was very
      significant in postmenopausal women and disappeared in premenopausal women. No
      significant difference was found in the fraction of proliferating cells between
      NAH and atypical hyperplasia (AH): 1.15 +/- 1.14% for NAH versus 1.26 +/- 1.19%
      for AH. In CIS and in invasive carcinoma (ICA), a significant increase in the
      percent of BrdU-labeled cells was observed when compared to the normal epithelial
      cells or NAH (p < 0.001). No significant difference was found in the values of
      BrdU-labeled cells between CIS and ICA (p = 0.29). The percent of BrdU-labeled
      cells in benign breast lesions, including fibroadenoma, papilloma, and sclerosing
      adenosis, did not differ from those of the normal epithelial cells. The
      menopausal status of the patients did not affect the proliferative activity in
      NAH or CIS. No correlation was found in the fraction of BrdU-labeled cells
      between the normal and hyperplastic epithelial cells (r2 = 0.012) or between NAH
      and CIS (r2 = 0.406) or between CIS and ICA (r2 = 0.429).

PMID- 7823589
TI  - A checklist for suitability of biomarkers as surrogate endpoints in
      chemoprevention of breast cancer.
AB  - By reference to a "checklist" of requirements for substances or processes to
      qualify as surrogate endpoint biomarkers, both malignin and antimalignin antibody
      are found to be suitable for use in breast cancer chemoprevention trials.
      Antimalignin has been shown to be highly specific and sensitive, modulatable and
      reversible, detectable early in appearance of malignancy and upon recovery
      therefrom, and differentially expressed in high-risk individuals as compared with
      the general population.

PMID- 7823590
TI  - Evaluation of surrogate endpoint biomarkers for ductal carcinoma in situ.
AB  - Ductal carcinoma in situ (DCIS) now accounts for 20-30% of all newly diagnosed
      breast cancers in centers which use mammographic surveillance as a standard part
      of the examination. The majority of these DCIS lesions, at least in the United
      States, are of very limited size, with mean estimated extents of 8-20 mm based on
      pathological examination. A small fraction of these are incidental microscopic
      features of the biopsy; the majority are detected on the basis of mammographic
      microcalcifications. These mammographically detected DCIS lesions are
      biologically heterogeneous, and this is reflected by their histology. Moreover, a
      number of recent independent studies have shown that the clinical outcome of
      patients, particularly those treated by breast conservation, is related to the
      presence of reproducible and identifiable histologic features, and possibly to
      certain immunohistochemically demonstrable gene markers as well. Nuclear and
      proliferative features of DCIS, as well as an evaluation of the periductular
      stroma, will be major focuses for the surrogate endpoint biomarker proposal.

PMID- 7823591
TI  - Target populations and strategies for chemoprevention trials of prostate cancer.
AB  - Chemoprevention trials usually target healthy populations and employ non-toxic
      chemicals in an effort to eliminate, reduce, or reverse premalignant lesions or
      early cancer. Recent efforts have been directed at short-term Phase II trials
      which rely on changes in surrogate endpoint biomarkers rather than cancer
      incidence reduction as an endpoint. Chemopreventive agents are chosen that are
      likely to produce a modulating effect on one or more biomarkers in prostate
      cancer, including extent and grade of morphometric, genetic, proliferative,
      differentiative, and regulatory biomarkers. Five target populations appear to
      have the greatest promise in chemoprevention trials for prostate cancer: (1)
      Patients with high-grade prostatic intraepithelial neoplasia, a microscopic
      lesion which is the likely precursor of some prostate cancers; (2) patients with
      early cancer treated by watchful waiting; (3) patients with cancer waiting for
      prostatectomy; (4) men at high risk of developing prostate cancer; and (5) men
      from the general population (normal risk of prostate cancer).

PMID- 7823592
TI  - Current and proposed biologic markers in prostate cancer: 1994.

PMID- 7823594
TI  - Tumor suppressor genes in prostatic oncogenesis.
AB  - Mutations of tumor suppressor genes are critical genetic alterations occurring
      during the genesis and progression of human cancer, and consequently are
      candidates for use as surrogate endpoint biomarkers. The two most intensively
      studied suppressor genes, retinoblastoma (Rb) and p53, are mutated in
      approximately 20-50% of advanced-stage prostate cancers, but only rarely in early
      tumors. The precise DNA base changes, especially those affecting p53, may yield
      clues to relevant carcinogenic mechanisms. Increased expression of p53 in
      neoplastic cells, as detected by immunohistochemistry, may indicate mutation or a
      physiological response to DNA damage. Allelic losses of chromosome arms 8p and
      16q are relatively common even in early prostate cancers. Quantitative
      measurement of allelic imbalance can be performed in preneoplastic or small
      neoplastic lesions, albeit with some technical challenge. The significance of
      whole-genome or regional allelic imbalance at various stages of prostatic
      oncogenesis has not been established.

PMID- 7823593
TI  - Apoptotic index as a biomarker in prostatic intraepithelial neoplasia (PIN) and
      prostate cancer.
AB  - Chemoprevention trials in prostate cancer would involve excessively long follow
      up if conventional endpoints of efficacy are used. Prostatic intraepithelial
      neoplasia (PIN) may be an appropriate surrogate endpoint for monitoring outcome
      during prostate cancer chemoprevention studies. To address the question of
      whether PIN could be stratified into "stable" PIN and PIN likely to progress to
      invasive cancer, we selected patients with a single focus of peripheral zone
      cancer with ipsilateral and contralateral high-grade PIN. Sixteen patients met
      these criteria from a series of 550 patients treated by radical prostatectomy. We
      examined the rate of apoptosis in PIN and prostate cancer tissues by quantifying
      the number of apoptotic bodies per hundred cells (apoptotic index) on hematoxylin
      and eosin stained histological sections. Significant differences (ANOVA: p <
      0.05) were detected between foci of prostatic intraepithelial neoplasia
      contralateral to the cancer and the cancer itself. There was no difference in the
      apoptotic index between a given cancer and a focus of PIN ipsilateral to the
      tumor in the same section. However, the range of apoptotic indices overlapped in
      all categories. Apoptotic indices appear to parallel the biological activity of
      PIN and malignant prostatic tissue, but may be of little benefit when used alone
      in monitoring the outcome of chemopreventive therapy in an individual patient.

PMID- 7823595
TI  - Quantitative and analytical cytology in historical perspective.
AB  - A brief review of the historical events leading to developments of image analysis
      and flow cytometry is presented. The principles, accomplishments, and pitfalls of
      both techniques of quantitation of cell components and specific applications to
      markers potentially useful in cancer chemoprevention are discussed.

PMID- 7823596
TI  - Adhesion molecules, extracellular matrix, and proteases in prostate carcinoma.
AB  - Immunohistochemical studies of prostate carcinoma reveal that most primary
      carcinomas, including high-grade tumors, are surrounded by a basal lamina
      composed of laminin, type IV collagen, and entactin. In addition to the expected
      laminin subchains A, B1, B2, subchains M and S are also found. Tenascin, found
      around normal glands, is seen in 60% of carcinomas. The basal cells of the normal
      gland express several integrin alpha units including alpha 2,3,4,5,6, and v. Both
      beta 1 and beta 4 subunits are observed. These integrin units are polarized at
      the base of the cells where they codistribute with the surrounding extracellular
      matrix. The integrin alpha 6 beta 4 is associated with hemidesmosomal-like
      structures, as detected by transmission electron microscopy (TEM). In carcinoma,
      the beta 4 is not observed and the alpha 6 and beta 1 subunits are variably
      expressed. The integrin expression in carcinoma is diffuse in the cytoplasmic
      membrane and not restricted to the basal aspects of the cell. In addition, type
      VII collagen and the BP 180 protein which are associated with hemidesmosomes are
      lost, although the BP 230, plectin, and HD1 proteins are variably expressed.
      Using immunohistochemistry and northern analysis we observed three
      metalloproteinases in prostate carcinoma--matrilysin, gelatinase A, and
      gelatinase B. Western blotting and zymogram analysis reveal that of these three,
      only matrilysin appears to be present in its active form. Recent in situ
      hybridization studies reveal focal expression of the matrilysin mRNA in 25/33
      primary carcinomas. Matrilysin also appears to be highly expressed in prostatic
      ducts and atrophic glands. Expression of the three metalloproteinases is also
      seen in prostatic intraepithelial neoplasia lesions.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7823597
TI  - Quantitative characterization of the frequency and location of cell proliferation
      and death in prostate pathology.
AB  - This paper evaluates the use of quantitative methods to accurately assess cell
      proliferation and death in untreated and treated prostate lesions. The analysis
      of proliferating cell nuclear antigen (PCNA)-stained nuclei allow precise
      evaluation of the proliferating cells and exact identification of their location
      in the progression of untreated prostatic intraepithelial neoplasia (PIN) to
      prostatic adenocarcinoma (PAC). The evaluation of the frequency and location of
      apoptotic bodies (ABs) gives accurate information on the apoptotic phenomenon in
      PIN compared to normal prostate (NP) and PAC. In fact, the frequency of ABs
      increases from NP to PIN to PAC and parallels that observed with PCNA. However,
      the AB-related values were approximately one-eighth to one-tenth of those
      obtained with PCNA immunostaining. Combination endocrine therapy (CET) decreases
      the proliferative activity and enhances the apoptosis phenomenon in NP, PIN, and
      PAC. This might indicate that CET could induce a certain degree of regression not
      only of PAC, but also of PIN.

PMID- 7823598
TI  - Evaluation of biomarkers in breast and prostate cancer.
AB  - p53, p185erbB-2, and epidermal growth factor (EGF) receptor are well
      characterized biomarkers in invasive adenocarcinoma of the breast and in ductal
      carcinoma in situ. erbB-2 Protein (p185erbB-2) must be identified clearly on
      cytoplasmic membranes while cytoplasmic expression is ignored for breast cancers
      to be classified as overexpressing p185erbB-2. For p53, nuclear staining and the
      percent positive cells are considered, but rules for "cut-offs" are not defined.
      Evaluation criteria for biomarkers in prostate cancer are preliminary and the
      "rules" may not be the same as for breast cancer. Because the initial methods of
      fixation and tissue processing can change both the pattern and intensity of
      immunohistochemical identification of specific antigens and localization of
      receptors may change after the receptor-ligand interactions, we evaluated the
      effects of fixation both on the immunolocalization and intensity of expression of
      p53, p185erbB-2, and EGF receptor. We also studied the patterns of p185erbB-2 and
      p53 expression in a series of breast cancers evaluated concomitantly with a group
      of prostate cancers. Our results confirm that p53 mutations are common in breast
      cancer and that there is strong expression of p185erbB-2 on the membranes of a
      subset of breast cancers. The patterns of staining for both p53 and p185erbB-2
      are different in prostate and breast cancers. A much lower proportion of prostate
      tumors than breast tumors have more than 10% of tumor cells with detectable
      nuclear p53 protein, but this proportion increases markedly in metastatic tumors
      or in primary stage D prostate cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7823599
TI  - Zonal origin of prostatic adenocarcinoma: are there biologic differences between
      transition zone and peripheral zone adenocarcinomas of the prostate gland?
AB  - Prostatic adenocarcinomas predominantly arise in the peripheral zone (PZ) of the
      organ; however, a significant subset of tumors (approximately 20%) originate in
      the transition zone (TZ). These tumors exhibit morphologic and growth pattern
      features suggestive of a lower degree of biologic aggressiveness. From our
      surgical pathology files, we identified 39 consecutive radical prostatectomy
      specimens in which discrete adenocarcinomas of both peripheral and transition
      zone origin were present. All specimens had been entirely embedded, step
      sectioned, and reviewed by two urologic pathologists. DNA content was determined
      by image analysis of Feulgen-stained tissue sections, and cellular proliferation
      was evaluated by immunohistochemical staining with MIB-1. The mean Gleason score
      for the PZ and TZ tumors was 6.7 and 5.6, respectively (p < 0.001). Of 15 cases
      analyzed to date, 8 PZ tumors and 2 TZ tumors were aneuploid (p = 0.055). The
      proliferation indices for the PZ and TZ tumors were 5.0% and 1.6%, respectively
      (p < 0.05). These findings confirm other reports, supporting the concept of
      biological differences between carcinomas of peripheral and transitional zone
      origin.

PMID- 7823601
TI  - Increasing the power of surrogate endpoint biomarkers: the aggregation of
      predictive factors.
AB  - A variable that predicts an outcome with sufficient accuracy is called a
      predictive factor. Predictive factors can be divided into three types based on
      the outcomes to be predicted and on the accuracy with which they can be
      predicted. These three types include risk factors, where the main outcome of
      interest is incidence and the predictive accuracy is less than 100%; diagnostic
      factors, where the main outcome of interest is also incidence but the predictive
      accuracy is almost 100%; and prognostic factors, where the main outcome of
      interest is death and the predictive accuracy is variable. Surrogate outcomes are
      predictive factors that are used for a purpose beyond the prediction of an
      outcome--surrogate outcomes are predictive factors that are substituted for the
      true outcome in order to determine the effectiveness of an intervention.
      Surrogate outcomes used in clinical trials are called intermediate endpoints and
      surrogate endpoints. Predictive factors used as surrogate outcomes have a poor
      accuracy rate in predicting the true outcome; aggregating risk factors increases
      predictive accuracy. Artificial neural networks effectively combine predictive
      factors. Aggregating predictive factors increases the degree of linkage of the
      surrogate outcome to the true outcome. The resulting increase in predictive
      accuracy allows enrollment of people most likely to benefit from intervention.
      This increases the trial's efficiency, reducing the number of people required to
      assess a chemopreventive agent.

PMID- 7823600
TI  - Retinoid modulation of biomarkers in oral leukoplakia/dysplasia.
AB  - Among the tissue, cellular, and molecular changes which take place during the
      development of squamous cell carcinoma (SCC) of the upper aerodigestive tract,
      only a limited number can be used as surrogate endpoint biomarkers (SEBs) in
      cancer chemoprevention trials. Molecular SEBs will be genes or gene products
      which can be measured accurately and reliably, are altered in intraepithelial
      neoplasia (dysplasia), correlate strongly with the true outcome (invasive
      cancer), and are modulated by a chemoprevention agent(s). To identify and
      modulate molecular SEBs in intraepithelial neoplasia of the upper aerodigestive
      tract, we studied expression of the epidermal growth factor receptor (EGFR),
      transforming growth factor-alpha (TGF-alpha), and HER-2/neu genes in oral
      leukoplakia before, during, and after treatment with 13-cis-retinoic acid, a
      vitamin A derivative. Four of nine patients treated for 3 months with 1 mg/kg/day
      of 13-cis-retinoic acid had complete resolution of their leukoplakia. Biopsies
      were taken of leukoplakia and adjacent normal-appearing mucosa before, during,
      and after treatment. Immunohistochemistry was performed using the BioGenex Super
      Sensitive Biotin-Streptavidin horseradish peroxidase detection system.
      Pretreatment expression of EGFR, TGF-alpha, and HER-2/neu in leukoplakia was
      increased when compared to normal-appearing mucosa. TGF-alpha expression
      decreased during treatment in leukoplakia, but not in normal-appearing mucosa,
      suggesting that TGF-alpha may serve as an intermediate endpoint in cancer
      chemoprevention trials.

PMID- 7823602
TI  - Standardization of immunobioassays as surrogate endpoints.
AB  - Despite centuries of scientific inquiry and medical effort, breast cancer remains
      one of the most dreaded human illnesses, emphasizing the need for prevention,
      early detection, and better management of these patients. Currently, newly
      recognized biomarkers are being examined as prognostic indicators to identify
      potentially aggressive cancers and to aid in planning treatment. Although the new
      prognostic factors are not yet firmly established, recent insights coupled with
      the availability of new biological markers have provided an opportunity to
      understand the initial genetic events leading to the development of breast
      cancer. Knowledge about those genetic events may provide opportunities for
      prophylactic intervention, improve our ability to predict breast cancer risk, and
      lead to strategies for early detection. Attention has focused on
      histomorphological changes and, to a lesser extent, cytomorphological changes in
      breast lesions associated with increased risk for subsequent breast cancer.
      However, the goal underlying the detection of early breast cancer is to
      distinguish patients who will develop breast cancer from those who will not. This
      task involves complex issues surrounding the selection, validation, quantitation,
      standardization, and population application of breast cancer biomarkers, and
      perhaps designing a protocol to control four major sources of cancer marker
      variability which may confound biomarker clinical application. These include
      biological and sampling diversity, variability of detection procedures, and
      validation against acknowledged disease endpoints. Immunocytochemistry has been
      applied extensively to assess the pattern of expression of different biomarkers
      in breast cancer. Immunocytochemical assays have permitted the localization of
      estrogen and progesterone receptors, oncogenes and tumor suppressor genes, growth
      factors, and other constituents at the cellular level, and also facilitated
      correlative analysis of morphology with specific expression of gene
      products.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7823603
TI  - An approach to preliminary studies of interlaboratory comparative results for
      estrogen and progesterone receptors.
AB  - Determining estrogen and progesterone (ER/PR) expression has clinical relevance
      in managing invasive breast carcinoma. Recent studies employing multivariate
      analyses which control for multiple factors have generally reaffirmed the role of
      ER and PR as prognostic determinants and management tools. Little information is
      available regarding the interlaboratory reproducibility of such testing in the
      clinical setting. Although ER/PR techniques based on cellular extracts have
      usually been used to make receptor determinations, immunohistological assays are
      gaining increasingly wider acceptance. The frequent admixture of non-neoplastic
      mammary parenchyma in tissue selected for ER and PR studies can yield false
      positive results when using the cellular extraction assays, but are easily
      recognized with an immunohistological approach. Furthermore, specimen economy is
      preserved--particularly when formalin-fixed, paraffin-embedded material is used
      for the immunohistological assay, an important issue as more small tumors are
      excised. The College of American Pathologists Cell Markers Resource Committee
      provides clinical laboratory professionals an opportunity to compare results with
      peers and to participate in an immunohistology education program. Designing such
      a program for ER and PR immunohistological assays is presented.

PMID- 7823604
TI  - Nuclear texture: can it be used as a surrogate endpoint biomarker?
AB  - Nuclear texture measurements are suggested to predict the progression/regression
      of precancerous lesions in breast, cervix, lung, and possibly other tissues.
      Nuclear texture features describe DNA distribution patterns in cell nuclei, and
      can be reliably measured by high resolution image cytometry, both in tissue
      sections as well as in single cell preparations such as smears from fine needle
      aspirates (FNAs) or cell suspension preparations. The cells must be stained with
      a stoichiometric DNA stain. For absorbance staining, the Feulgen-Thionin stain is
      one of the best performers used for DNA ploidy measurements using conventional
      image cytometry. Regression/progression information can be obtained from either
      diagnostic cell nuclei or from cell nuclei of normal surrounding tissue. Subtle
      changes in normal-appearing cells adjacent to malignant tumors are called
      malignancy associated changes (MACs) and can be detected by nuclear texture
      measurements. We postulate that measurements of texture features can also be
      employed as surrogate endpoint biomarkers (SEBs).

PMID- 7823605
TI  - Surrogate endpoint biomarker assays in phase II chemoprevention clinical trials.
AB  - Surrogate endpoint biomarker (SEB) assays carried out in rodent models have
      benefitted from large amounts of available colonic tissue, abundant well-aligned
      colonic crypts, and population groups with fairly uniform biological
      characteristics. In contrast, SEB assays in human colon studies have often been
      carried out on small groups of subjects, without the advantages inherent in
      rodent studies. Some factors that contribute to variations in human colon SEB
      assays include differences in genetic background, the extent and duration of
      previous colonic diseases, degree of previous chronic irritation to the colonic
      mucosa, the initial levels of nutrients ingested prior to the study,
      administration of large volumes of fluid prior to SEB measurement which induce
      hypermetabolic and then quiescent changes in the mucosa, failure to use strict
      morphologic criteria in counting colonic crypts, and availability of only a small
      number of crypts for analysis. Measurements of adenoma recurrence over short
      durations are limited by factors that include a large potential miss-rate of
      small adenomas, a window of observation with short duration which limits the
      stage of adenoma observed, and the consequent inability to measure mechanisms
      that a chemopreventive intervention is affecting in a different stage of adenoma
      development.

PMID- 7823606
TI  - Methodological problems in the use of rectal cell proliferation as a biomarker of
      colorectal cancer risk.
AB  - Clinical and experimental studies have shown that the carcinogenic process of
      colorectal mucosa is linked to the development of proliferative abnormalities
      which precede the occurrence of morphological abnormalities such as epithelial
      dysplasia. In humans, proliferative defects have been demonstrated in the normal
      rectal mucosa of population groups at risk for colon cancer. Several techniques
      are available to study cell kinetics in the gastrointestinal mucosa. Each
      explores different aspects of cell proliferation. We have attempted to evaluate
      the correlation between various techniques in the normal rectal mucosa of high
      risk patients. We found a good correlation between bromodeoxyuridine (BrdU)
      labeling index and the mucosal activity of the enzyme ornithine decarboxylase,
      and between tritiated thymidine and the percentage of cells in the S phase of the
      proliferative cycle as determined by flow cytometry. However, these correlations
      concern only labeling indices, which can be influenced by physiological events,
      such as active inflammation or increased cell loss. It may not be the most
      reliable proliferative marker of cancer risk. Moreover, methods using cells
      isolated from homogenized tissue do not allow us to evaluate the pool of cells
      which are examined nor the distribution of proliferating cells within the tissue.
      For example, an inflamed mucosal specimen is highly infiltrated with inflammatory
      cells which can interfere with the measurement of epithelial cell proliferation.
      Nevertheless, the labeling index may be normal even in patients at high risk. For
      these reasons, we think that the most reliable methods are those using tissue
      culture, such as tritiated thymidine or BrdU uptake and proliferating cell
      nuclear antigen (PCNA) immunostaining.

PMID- 7823607
TI  - Methodological aspects of using immunohistochemical cell proliferation biomarkers
      in colorectal carcinoma chemoprevention.
AB  - In vitro uptake of bromodeoxyuridine (BrdU), expression of proliferating cell
      nuclear antigen (PCNA), and expression of antigen Ki-67 as revealed by the MIB-1
      antibody in fixed and embedded tissues have been regarded as markers of cell
      proliferation in colorectal tumor progression. Proliferation distribution
      abnormalities in high-risk mucosa have been illustrated in detail by BrdU
      labeling of cells in S phase, whereas PCNA and MIB-1 are less informative at this
      stage of carcinogenesis. The reliability of BrdU labeling is, in any event,
      dependent on optimization of its tissue uptake and diffusion. Neoplastic
      deregulation of the synthesis and expression of PCNA, coupled with striking
      variations in nuclear immunostaining intensity, imposes caution on its use as an
      intermediate biomarker in intestinal chemoprevention. Validation of MIB-1 must
      await the standardization of some of the critical procedures (e.g., treatment
      with microwaves) of antigen retrieval.

PMID- 7823608
TI  - Reliability of rectal epithelial kinetic patterns as an intermediate biomarker of
      colon cancer.
AB  - The use of biomarkers to assess cancer risk is based on the model of cancer as a
      multistep process; such markers are assumed to reflect an early stage in this
      process. A valid biomarker of risk must therefore show differential expression in
      normal and high-risk subjects, as well as quantitative correlation with the stage
      of carcinogenesis. It should also be easy to detect in small tissue specimens and
      responsive to modulation by chemopreventive agents. Cell proliferation is one of
      the most widely investigated markers of cancer risk. Case-control studies have
      shown that epithelial cell proliferation parameters, assessed in rectal mucosal
      biopsies by means of in vitro autoradiographic or immunohistochemical techniques,
      can discriminate between populations with normal and high risks for colon cancer.
      However, we recently reviewed rectal biopsies from 152 subjects (43 controls, 84
      with adenomas, 25 resected for colon cancer) processed for in vitro 3H-thymidine
      autoradiography, and attempted to correlate various proliferative parameters with
      clinical and pathological variables by means of multiple regression analysis.
      Elevations of total crypt labeling indices (LIs), particularly upper crypt LIs,
      were significantly associated with the presence of adenomatous polyps, although
      subsequent linear discriminant analysis revealed that the accuracy of LIs in
      discriminating between polyp patients and controls was actually quite low.
      However, we have also found that upper crypt LIs are reliable predictors of
      adenomatous polyp recurrence. Repeated evaluations of rectal proliferative
      indices over a 2-year post-polypectomy follow-up of 40 patients with colonic
      adenomas revealed substantial stability.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7823609
TI  - Validation of proliferation indices as surrogate endpoint biomarkers.
AB  - During the 1990s, research interest in the use of chemopreventive agents to
      reverse human colon carcinogenesis increased exponentially. In parallel, there
      has been an increase in the need for putative surrogate endpoint biomarkers
      (SEBs) of cancer risk. Since the hallmark studies of Lipkin et al. and Terpstra
      et al., among others, the rate and patterns of rectal mucosal proliferation have
      been established as intermediate biomarker endpoints for colon cancer risk,
      modulated by potential chemopreventive agents including calcium, wheat bran
      fiber, and nutritional stress diets. Researchers rely heavily on these rectal
      mucosal proliferation indices as surrogate endpoints to evaluate the relative
      efficacy of various chemopreventive intervention strategies. Standardization
      through quality control/quality assurance (QC/QA) programs which continuously
      validate the accuracy, reproducibility, and variability of these indices is
      increasingly needed. Along with many others, we have attempted to validate 3H
      thymidine and bromodeoxyuridine labeling indices in rectal mucosal biopsies as
      reliable SEBs. In this manuscript we outline a series of QC/QA steps that can be
      followed in the validation process for new as well as "old" biomarkers prior to
      their use as primary efficacy surrogate endpoints for chemopreventive agent
      intervention trials.

PMID- 7823611
TI  - If there is gold in the labeling index hills, are we digging in the right place?
AB  - Surrogate endpoint biomarkers (SEBs) are a necessary tool for cancer
      chemoprevention studies. However, the efficiency gain from using an SEB is
      purchased at a price. SEBs need to go through a developmental process, in which
      their behavior is understood in detail, before they can be used broadly in
      chemoprevention work. Examples of problems that need to be overcome are presented
      for labeling indices of cell proliferation. Since literature-based meta-analyses
      are not feasible for SEBs, a data archive is proposed in order to strengthen the
      development phase by pooling data across studies.

PMID- 7823610
TI  - Rectal epithelial cell proliferation: comparison of errors of measurement with
      inter-subject variance. Australian Polyp Prevention Project Investigators.
AB  - If measures of rectal epithelial kinetics are to be used on a large scale, or as
      part of multicenter studies, the variance of repeated measures must be
      sufficiently small to detect the effect of clinical status and dietary, or
      chemoprevention interventions. Errors in measurement can be categorized as intra
      reader (sigma 2I), inter-biopsy (sigma 2B), inter-laboratory (sigma 2L), and
      inter-reader (sigma 2R); the sum of these (sigma 2T) when compared to inter
      subject variance (sigma 2S) is a measure of the precision with which cell
      kinetics can be estimated for a given subject. We estimated the variances of the
      component errors in four separate experiments, each involving 6 to 10 subjects,
      using the proliferating cell nuclear antigen (PCNA) technique. PCNA labeling
      index variances for a single laboratory study were sigma 2I = 0.02-0.07 and sigma
      2B = 0.08-0.15. Inter-laboratory and inter-reader variances were sigma 2L = 0.08
      and sigma 2R = 0.03. Summing the errors applicable within a laboratory gives a
      rounded estimate of 0.15. For inter-laboratory studies the total error (sigma 2T)
      is greater, estimated in our two-laboratory study as 0.3. In a separate study,
      the variation between biopsies (sigma 2B) could be accounted for by the variation
      between crypts within biopsies; an acceptable level of accuracy is achieved after
      counting 20-30 crypts. In contrast to the measurement errors, the variance
      between subjects, which includes a treatment effect of diet, was larger,
      estimated to be between 0.75 and 1.30.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7823612
TI  - Summary of recommendations for colonic biomarker studies of candidate
      chemopreventive compounds in phase II clinical trials.
AB  - New genetic, morphologic, proliferative and differentiation-associated biomarkers
      are available for study in Phase II chemoprevention clinical trials. These
      biomarkers have potential as surrogate intermediate endpoints for cancer
      incidence and eventual tumor inhibition. At this meeting, approaches to improve
      the standardization and quality control of biomarker assays were considered.
      Useful biomarkers should be amenable to quality control monitoring; sensitive,
      specific, and precise; sensitive to modulation by chemopreventive agents; and
      simple enough to be performed routinely in research or clinical laboratories.
      Human studies have more factors that contribute to biomarker assay variation than
      rodent studies. These include: (1) wider differences in genetic background of
      study subjects; (2) differing extent and duration of previous colonic diseases;
      (3) varying amounts of chronic irritation in the colonic mucosa of "normal"
      subjects induced by exposure to dietary and other factors; (4) differing initial
      levels of study nutrients ingested prior to the study; (5) administration of
      fluids prior to biomarker measurement which are followed by biopsies after
      hypermetabolic changes become quiescent; (6) failure to use strict morphologic
      criteria in counting fewer available human colonic crypts; (7) amplifying field
      variations in colonic mucosa by decreasing the number of colonic crypts counted;
      (8) colonoscopic miss-rate of adenomas; (9) a clinical trial window of
      observation of short duration which limits the stage of adenoma development that
      is measured; and (10) failure to measure the activity of a chemopreventive agent
      during the stage of adenoma development in which it is active. Some of these
      points are relevant to chemopreventive agents used in clinical trials involving
      other organs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7823613
TI  - Biomarkers of breast hyperplasias and in situ carcinomas: an overview.
AB  - Hyperplasia and carcinoma in situ of the breast are thought to be non-obligatory
      precursor lesions of invasive breast carcinoma. Such lesions are detected more
      and more through mammography. A subjective, clinically relevant histopathological
      classification system of preinvasive breast lesions has been established by Page
      and co-workers in large groups of patients with long term follow-up. Attempts
      have been made to objectify the changes within the different preinvasive entities
      using quantitative techniques. Furthermore, some clues have been found as to the
      molecular background of breast oncogenesis. In this paper, an overview of
      possible surrogate endpoint biomarkers of breast hyperplasia and carcinoma in
      situ is presented.

PMID- 7823614
TI  - Single-day apolipoprotein E genotyping.
AB  - Current methods of genotyping an individual's apolipoprotein (ApoE) alleles
      involve time-consuming separations of digested fragments on high-percentage non
      denaturing polyacrylamide gels. However, it is possible to separate the fragments
      quicker and with greater ease using agarose.

PMID- 7823615
TI  - Determination of extracellular bicarbonate and carbon dioxide concentrations in
      brain slices using carbonate and pH-selective microelectrodes.
AB  - The extracellular pH of the brain is subject to shifts during neural activity. To
      understand these pH changes, it is necessary to measure [H+], [HCO3-], [CO3(2-)]
      and [CO2]. In principle, this can be accomplished using CO3(2-) and pH-sensitive
      microelectrodes; however, interference from HCO3- and Cl-, and physiological
      changes in [HCO3-], complicate measurements with CO3(2-) electrodes. Calibration
      requires knowledge of slope response, interference constants and corrections for
      [HCO3-] shifts. We show that when [HCO3-] is altered at constant [CO2] in the
      absence of Cl-, the HCO3- interference cancels and the Nikolsky equation reduces
      to the Nernst equation for CO3(2-). Measurement of CO3(2-) slope response by this
      method yielded a value of 28.5 +/- 0.72 mV per decade change in [CO3(2-)]. In Cl(
      )-containing solutions, interference coefficient for HCO3- and Cl- were
      determined by altering [HCO3-] at constant [CO2], changing [CO2] at constant
      [HCO3-], then solving the simultaneous Nikolsky equations for each transition.
      The mean interference constants corresponded to selectivity ratios of 245:1 and
      1150:1 for CO3(2-) over HCO3- and Cl- respectively. To correct for possible
      changes in [HCO3-], the equilibrium relation between CO3(2-) and HCO3- was
      substituted into the Nikolsky equation to yield an equation in [CO3(2-)] and
      [H+]. By simultaneously measuring shifts in [H+] with a pH microelectrode, this
      equation is readily solved for [CO3(2-)]. These methods were tested by measuring
      [HCO3-] and [CO2] in experimental solutions, and in the extracellular fluid of
      rat hippocampal slices.

PMID- 7823616
TI  - Intraperitoneal injections of Fluorogold reliably labels all sympathetic
      preganglionic neurons in the rat.
AB  - The ability of intraperitoneal injections of a retrograde neuronal tracer,
      Fluorogold, to label the entire population of sympathetic preganglionic neurones
      was tested with a double-labelling strategy. Animals were injected
      intraperitoneally (i.p.) with Fluorogold, while Fast Blue or subunit B of cholera
      toxin were injected into a peripheral autonomic ganglion or into the adrenal
      gland. Sympathetic preganglionic neurones were then examined for retrogradely
      transported tracers. In all cases, preganglionic neurones labelled with Fast Blue
      or cholera toxin also contained Fluorogold, indicating that i.p. injections of
      Fluorogold do reliably label the entire population of sympathetic preganglionic
      neurones.

PMID- 7823617
TI  - A new approach to the estimation of post-synaptic potentials in human
      motoneurones.
AB  - A new method is described for estimating the shape of the compound post-synaptic
      potentials evoked by stimuli in human motoneurones. The method is based on
      changes in the duration of the interspike intervals in motor-unit spike trains
      that are time-locked to the stimulus. This is particularly helpful in estimating
      the profile of long-latency slow rise-time post-synaptic potentials that are
      difficult to estimate with other methods. The method is simple to apply and the
      analysis is readily implemented on a personal computer.

PMID- 7823618
TI  - A simple technique for the estimation of regional blood content in brain.
AB  - A simple and inexpensive technique is described for the assessment of regional
      cerebral blood volume (CBV) using a color reaction based on the pseudoperoxidase
      activity of hemoglobin. Cryostat sections are placed on a commercially available
      reagent strip originally designed for quantitative estimation of blood content in
      urine. After melting of the brain section, a blue color reaction appears which is
      darker in areas with higher hemoglobin content. The image is analyzed by a
      computerized image-processing system and evaluated by standards prepared from
      brain homogenate with different hemoglobin content. From the optical density
      data, regional CBV is calculated with correction for the difference between
      microvascular and large vessel hematocrit. The method was validated by a
      radiolabel procedure. Values of regional CBV are reported in gray matter areas of
      control rabbits and in brains embolized by autologous clot. This simple
      inexpensive technique is a useful supplementary tool in multiparametric metabolic
      studies.

PMID- 7823619
TI  - Automating the generation and collection of rate-frequency functions in a curve
      shift brain stimulation reward paradigm.
AB  - The electrical self-stimulation paradigm has proven to be very useful in research
      aimed at delineating the neural substrates involved in reward-related learning.
      Of the procedures currently employed the curve-shift method is among the more
      useful since it distinguishes between treatment effects on reward and
      performance. This method involves generating and plotting rate-frequency
      functions and quantifying the effects of experimental manipulations on reward by
      measuring the degree of lateral shift in these functions. We have designed a
      computerized system that automatically generates and collects descending rate
      frequency functions from self-stimulating rats. The 3 main units of this system
      consisted of a 6809 micro-controller, a programmable timer logic board and a
      constant current source. The micro-controller and programmable timer operated on
      custom written software that monitored lever pressing in the operant chambers and
      controlled stimulation parameters to generate and record rate-frequency
      functions. The present report describes this system and presents some typical
      data collected from rats self-stimulating on ventral tegmental electrodes before
      and after the administration of intra-accumbens vehicle (0.5 microliter distilled
      H2O), (+)-amphetamine (20.0 micrograms/0.5 microliter), quinpirole (10.0
      micrograms/0.5 microliter) and systemic quinpirole (1.0 mg/kg), all dopamine
      agonists. Stimulation consisting of 300-ms trains of cathodal rectangular pulses
      (0.1 ms) was available in 50-s trials. The number of pulses per train was
      decreased logarithmically from a value that sustained maximal responding to one
      that would not sustain responding. Self-stimulation thresholds were obtained by
      fitting the Gompertz growth model to the data and calculating the point of
      maximal acceleration of the sigmoidal curve. It was found that the present system
      generated and collected rate-frequency functions similar to those that have been
      obtained manually in previous experiments. The data showed that the system was
      sensitive to both central and systemic pharmacological manipulations by producing
      lateral and vertical shifts of the rate-frequency functions, indications of
      reward and motor effects, respectively. It was concluded that the present design
      was useful in conducting entire self-stimulation sessions that required minimal
      monitoring by the experimenter.

PMID- 7823620
TI  - Component analysis of the responses of sensory neurons to combined sinusoidal and
      triangular stimulation.
AB  - A method for quantitative estimation of sensory neuron sensitivity to small
      sinusoidal stimuli in the presence of sizable background drift (in the stimulus
      or response) was developed. The performance of the method was tested by analyzing
      the responses of 17 muscle spindle primary (Ia) afferent neurons to concomitant
      sinusoidal and triangular stretching of the soleus muscle. The efficacy and
      accuracy of several variations of the method were examined. The variations
      included the use of probability density (PD) and average frequency (AF)
      histograms as the basis for calculations and two different algorithms for the
      decomposition of responses to combined sinusoidal and triangular stimulation. One
      algorithm called the 'inherent-drift' method exploited the inherent half-cycle
      repeat property of a sine wave to extract the drift component. Another algorithm
      called the 'forced-drift' method first estimated the drift by linear regression
      to a response to triangular stimulation alone. The drift estimate (a slope value)
      was then subtracted from the response to combined sinusoidal and triangular
      stimulation of the same triangular (background) velocity. A comparison of the
      performance of the drift correction method applied either to PD or AF histograms
      revealed no significant differences in the estimates of sinusoidal modulation.
      The limitations of the AF method were manifest primarily by phase lags at low
      mean levels of action potential discharge. Calculation of the response parameters
      using the 'inherent-drift' correction procedure proved straightforward as long as
      there were at least two pairs of non-empty bins in the sine-cycle histograms on
      which to base the estimate of drift. The method remained effective in determining
      sinusoidal sensitivity in the face of distinct non-linearities (harmonic
      distortions) in the sine-cycle histograms. However, estimates of slope and the
      extraction of sinusoidal phase by the 'inherent' slope correction method became
      subject to large errors. Under such circumstances, more reliable estimates could
      be obtained by using the forced drift-correction method instead. The importance
      of extracting the drift component prior to estimating the sinusoidal response
      parameters was evaluated experimentally and theoretically. In general, omission
      of a drift correction introduced a large bias in the estimates of the phase of
      sinusoidal response, whereas the estimate of sinusoidal modulation was rather
      insensitive. Experimental findings were fully accounted for by theoretical
      considerations. Analytically derived relationships identified low- and high-risk
      regions more clearly for the estimate of sinusoidal modulation than of phase. The
      relationship between biased modulation estimate and underlying drift showed
      minima characteristics with a low-risk region, where absolute errors and
      dependence on slope variations were small.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7823621
TI  - Sources of errors in different single-electrode voltage-clamp techniques: a
      computer simulation study.
AB  - The use of voltage clamp with a single electrode has been useful in estimating
      kinetic parameters for a number of ionic whole-cell currents. There are two main
      types of such a technique: discontinuous voltage clamp (dSEVC) (Brennecke and
      Lindemann, 1974), and continuous voltage clamp (cSEVC) (Hamill et al., 1981). We
      have studied, by means of computer simulations, the performance of both types of
      clamp on estimating activation kinetics parameters of a typical neuronal Ca2+
      current. Deviations from the theoretical values are shown to be sensitive on both
      set-up and cell properties. Both types of clamp are shown to lose voltage control
      when either access resistance or absolute membrane conductance are increased. In
      contrast, changes in membrane capacitance affect differently to the estimates
      obtained by the two types of clamp. Cell size is also shown to affect cSEVC
      performance but not that of dSEVC. The nature and magnitude of errors obtained by
      using both types of clamp in different situations are discussed.

PMID- 7823622
TI  - A method for 2D reconstruction of intracellularly labeled neurons from sequential
      sections.
AB  - A technique for 2D reconstruction of intracellularly labeled neurons from
      sequential sections is described. The system consists of a Charged Coupled Device
      camera mounted on a microscope, a videomixer and a IBM-compatible PC with a
      framegrabber. The neurons (interneurons from the spinal cord of the cat) were
      labeled iontophoretically by horshradish peroxidase and subsequently cut in 60
      microns sections. The sections were aligned using the video mixer by fitting the
      cut dendrites and axon from one section with their counterparts in the following
      section. The images were then digitized in the PC where they were fused to create
      a superimposed picture of the aligned parts of the neuron; a 2D reconstruction
      was created.

PMID- 7823623
TI  - Calcium homeostasis in the presence of fura-2 in neurons dissociated from rat
      nucleus basalis: theoretical and experimental analysis of chelating action of
      fura-2.
AB  - Intracellular calcium ions (Ca2+) play important roles in cell functions.
      Measurements of intracellular calcium ion concentration ([Ca2+]i) are often made
      with the fura-2 fluorescence recording technique in various preparations
      including neurons. Fura-2 has, however, a Ca(2+)-chelating action which
      complicates the interpretation of experimental results. In this report the
      chelating action of intracellular fura-2 was studied by means of computer
      simulations. The chelating action of an endogenous Ca(2+)-binding protein,
      calmodulin, was also estimated. Furthermore, whole-cell patch-clamp recordings of
      calcium currents (ICa) and fura-2 microfluorimetric recordings of [Ca2+]i were
      simultaneously made from neurons which were acutely dissociated from the rat
      nucleus basalis. Since Ca2+ influx can be initiated and terminated by using the
      voltage-clamp technique, the relationship between Ca2+ influx and rapid [Ca2+]i
      increase was examined. The present theoretical evaluations and experimental
      results disclosed the relationship between fura-2 and endogenous Ca(2+)-binding
      proteins; fura-2 at low concentration (10 microM) did not substantially affect
      the endogenous Ca2+ buffering mechanisms, but at high concentration (200 microM)
      effectively buffered cytosolic Ca2+ instead of endogenous Ca2+ buffers. Calcium
      homeostasis in neurons is furthermore discussed.

PMID- 7823624
TI  - Finger sudorometry and assessment of the sudomotor drive.
AB  - Sudorometry of the finger was carried out using the ventilated capsule method,
      the aim being to use the level of relative humidity within the sudorometer as an
      indirect measure of the sudomotor drive. Subjects inserted a finger through a
      diaphragm of a finger-shaped, temperature-controlled chamber which also contained
      the humidity sensor. Manoeuvres known to alter the sudomotor drive produced
      changes in chamber humidity. The relative humidity within the sudorometer became
      constant after local anaesthesia of the digital nerves and after upper limb
      sympathectomy, suggesting that fluctuations in the sudorometer output were
      dependent upon an intact autonomic nervous system. In an environment in which
      temperature was controlled and arousal effects from the process of measurement
      were minimised, chamber humidity always increased during a Stroop test, providing
      a rapid means of indirectly assessing sudomotor drive mechanisms.

PMID- 7823625
TI  - Motor-unit firing frequency can be used for the estimation of synaptic potentials
      in human motoneurones.
AB  - This paper describes a new method that uses the frequency of firing of motor
      units to estimate the stimulus-induced net post-synaptic potential (PSP) and the
      synaptic noise in the membrane of voluntarily active human motoneurons. Unlike
      the peri-stimulus time histogram (PSTH) which is the most commonly used method
      for assessing stimulus-induced synaptic potentials in human motoneurones, this
      new approach overcomes contamination of the results caused by the synchronizing
      effect of the stimulus on the firing pattern of the motor units. However, even
      after overcoming the contamination by synchronized firing, the new method does
      not directly represent the true net synaptic potential in the motoneurone
      membrane. Therefore, a new term estimated net synaptic potential (ENSP) has been
      introduced. This term highlights the fact that the stimulus-induced net synaptic
      potential has been determined indirectly and that the size and the shape of this
      synaptic potential may depend on the level of activity of the recording medium
      (i.e., pre-stimulus firing frequency of the motor unit). This paper also puts
      forward a normalization procedure that allows the value of the ENSP and the
      amplitude of the synaptic noise to be read from the ENSP graph. The normalization
      procedure, therefore, allows comparisons of those values within and between
      subjects.

PMID- 7823627
TI  - Reading patients--cautions and concerns.

PMID- 7823626
TI  - The Harriet W. Sheridan Literature and Medicine Lectureship and Forum, Brown
      University School of Medicine. Introduction.

PMID- 7823628
TI  - Beyond the Ouija board: dialogue and heteroglossia in the medical narrative.

PMID- 7823629
TI  - Radioactive body politics: AIDS as nuclear text.

PMID- 7823630
TI  - The giant in literature and in medical practice.

PMID- 7823631
TI  - "Why Bao-yu can't concentrate": attention deficit disorder in The story of the
      stone.

PMID- 7823632
TI  - "Fated boy": Karpman's drama triangle and Melville's Billy Budd.

PMID- 7823633
TI  - A roster of twentieth-century physicians writing in English.

PMID- 7823634
TI  - Decline in natural killer cell-mediated immunosurveillance in aging mice--a
      consequence of reduced cell production and tumor binding capacity.
AB  - The mechanism(s) responsible for the functional deficiencies in aging mice of
      natural killer (NK) cells, the lymphocytes active in early neoplasia development,
      are unknown. The aim of the present study was to examine the effect of
      indomethacin, a prostaglandin synthetase inhibitor, and recombinant interleukin-2
      (rIL-2), an NK cell stimulant, on the NK cell numbers and function of aging mice.
      This combination is highly effective in inducing proliferation and activation of
      the NK cells in young adult mice. Ten- to 13-month-old DBA/2 mice received either
      indomethacin daily for 9 days in their drinking water, or rIL-2 twice a day for 4
      days, or both agents combined. Untreated aging mice had 50% fewer splenic NK
      cells than did young adult (5-8 weeks) DBA/2 mice, although bone marrow contained
      NK cell numbers similar to that of young adult mice. Neither indomethacin alone,
      rIL-2 alone nor the combination of both could induce an increase in NK cell
      numbers or function in aging mice. Radioautography combined with immunoperoxidase
      labelling techniques revealed that the production of new NK cells from the bone
      marrow of aging mice was significantly reduced relative to that of young adult
      mice. This was reflected in low numbers of newly formed NK cells accumulating in
      the spleens of aging mice. The target binding capacity, a necessary precytolytic
      event, of aging mouse NK cells was also reduced compared to that of young adult
      mice. The results suggest that the functional deficiencies of aging mouse NK
      cells are a consequence of multiple factors including an absolute loss of NK
      cells resulting from a reduced production of such cells in the bone marrow and a
      decreased capacity of NK cells to bind their tumor targets.

PMID- 7823635
TI  - The influence of age on supraoptic nucleus glial cells of the mouse.
AB  - In 2-year-old mice, astrocytes of the supraoptic nucleus (SON) of the
      hypothalamus, placed in close contact with the meningeal covering contained
      concentric arrangements of cisterns in their cytoplasm called glial concentric
      bodies (GCBs). They are formed by a variable number of flattened cisterns without
      pores, and no anastomosis was observed between adjacent cisterns. Rough
      endoplasmic reticulum (RER) cisterns do not show continuity with fully developed
      GCBs, although a close continuity between RER cisterns and GCBs was present in
      images suggesting GCB formation. Concomitantly with the appearance of GCBs,
      ventral neurosecretory neurons of the SON showed a cytoplasmic membrane
      reinforced by the apposition of glial prolongations. The possible origin and
      function of these GCBs and lamellae are discussed here.

PMID- 7823636
TI  - Effect of ethylene on selective ribosomal cistron regulation in quiescent and
      senescent onion leaf base tissue.
AB  - Excised pieces of tissue from four regions (base, equator, near-apex, and apex)
      of yellow, sweet Spanish onion bulbs were treated with ethylene in an attempt to
      activate minor nucleolar organizer regions (NORs). In the quiescent equatorial
      and near-apical regions, major nucleoli in control and ethylene-treated tissue
      increased in size and changed morphologies. The minor NORs were expressed only in
      the ethylene-treated tissue. These data confirm and extend our previous findings.
      In the quiescent basal region, major nucleoli increased in size and changed
      morphology from round to oval, elongated-oval and dumbbell shapes in both control
      and ethylene-treated tissue. However, the number of elongated-oval and dumbbell
      types were one-third that observed in equatorial and near-apical tissue. Minor
      NORs were not expressed. We infer that the responses of the major nucleoli and
      the inability to activate minor NORs were due to hormone interactions that affect
      the expression of rRNA cistrons (methylation-demethylation of CpG sites in the
      external spacers) in this basal (meristematic) region. In the senescing apical
      region, major nucleoli in control and ethylene-treated tissue did not change in
      size or morphology and ethylene had no effect on minor NORs. We infer that the
      cells in the apical region had passed the point of no return in the senescence
      pathway. We propose that the inability to activate major and minor NORs in
      senescing tissue is one of the earliest symptoms of cellular senescence and is
      associated with karyoskeleton degeneration.

PMID- 7823637
TI  - On a causal mechanism of chronic thymic involution in man.
AB  - The age-associated chronic thymus involution is interpreted to occur due to
      cytolytic depletion of thymic stromal tissue whose cells present altered self
      peptides. Using simplified assumptions and based on morphometric data on thymic
      involution in man, the chance for a single protein to be altered is estimated to
      be in the range of 2-4 x 10(-6) per year. The corresponding mutation rate is
      compatible with that derived from both evolutionary and direct studies, thus
      supporting the proposed model.

PMID- 7823638
TI  - Influence of treatment with L-deprenyl on the structure of the cerebellar cortex
      of aged rats.
AB  - Treatment with L-deprenyl increases mean and maximum life span in the rat and
      reverses memory and learning deficits associated with old age. Since only sparse
      information is available concerning the influence of L-deprenyl administration on
      the aging brain microanatomy, we have investigated the effect of long-term
      treatment with L-deprenyl on the structure of the cerebellar cortex in the aged
      rat. The cerebellar cortex was used since it represents a useful model for
      assessing age-related changes in nervous system anatomy and function. Male
      Sprague-Dawley rats were treated from the 19th to the 24th month of age with a
      daily oral dose of 1.25 mg/kg or 5 mg/kg L-deprenyl. Age-matched rats were left
      untreated and used as a control group. Eleven-month-old untreated rats were used
      as an adult reference group. The density of Purkinje and granule neuron profiles
      as well as the intensity of Nissl's staining within the cytoplasm of Purkinje
      neurons were reduced in 24-month in comparison with 11-month rats. Moreover, an
      increased accumulation of lipofuscin was noticeable in the cytoplasm of Purkinje
      neurons of old rats as well as an increase in MAO-B activity in the molecular
      layer of the cerebellar cortex. The two doses of L-deprenyl increased the density
      of both Purkinje and granule neuron profiles and the intensity of Nissl's
      staining in the cytoplasm of Purkinje neurons and reduced lipofuscin deposition
      within Purkinje neurons. The lower dose of L-deprenyl caused only a slight
      decrease in MAO-B activity, whereas the 5-mg/kg/day dose remarkably reduced it.
      These results suggest that long-term treatment with L-deprenyl counters the
      expression of some age-related microanatomical changes in the rat cerebellar
      cortex. The possible independence of the effects of the compound on age-related
      microanatomical changes of the cerebellar cortex and on MAO-B inhibitory activity
      is discussed.

PMID- 7823639
TI  - Effect of treatment with the dihydropyridine-type calcium antagonist darodipine
      (PY 108-068) on the expression of neurofilament protein immunoreactivity in the
      cerebellar cortex of aged rats.
AB  - The effect of long-term treatment with the dihydropyridine-type Ca2+ antagonist
      darodipine (PY 108-068) on the expression of neurofilament (NF) protein (200 kDa
      NF subunit) immunoreactivity in the cerebellar cortex of aged male Wistar rats
      was assessed using immunohistochemical techniques associated with image analysis.
      In 12-month-old rats (adult) used as reference animals, 200 kDa-NF subunit
      immunoreactivity was observed primarily in axons of basket neurons localized in
      the molecular layer and surrounding the cell body of Purkinje neurons. A specific
      immunoreactivity was also found in the initial segment of Purkinje neuron axons,
      and in axons of the white matter of the cerebellar cortex. In 24-month-old rats
      (aged) a significant decrease in the area occupied by immunoreactive structures
      was noticeable in comparison with adult animals. A 6-month treatment (from the
      18th to the 24th month of life) with an oral daily dose of 10 mg/kg of darodipine
      restored in part the expression of 200 kDa-NF subunit immunoreactivity in the
      cerebellar cortex. These data indicate that treatment with the dihydropyridine
      type Ca2+ channel blocker darodipine is able to counter in part the age-related
      loss in the expression of NF protein in the rat cerebellar cortex. This suggests
      that darodipine may reduce neuronal cytoskeletal changes occurring in aging and
      in neurodegenerative disorders.

PMID- 7823640
TI  - Predicting inpatient costs with admitting clinical data.
AB  - Hospital cost-containment programs should themselves be cost-effective, targeting
      high-cost physicians (which requires adjusting for case mix) and patients (which
      requires early identification). In this study, clinical data available within 24
      hours of admission from an electronic medical record system were used to develop
      statistical models to predict hospital costs. In this retrospective analysis of
      clinical data and diagnosis-related groups (DRGs), study subjects were 2,355
      patients admitted for at least 1 day to the medicine service at an urban teaching
      hospital with sophisticated electronic medical records. Of these 2,355 patients,
      1,663 (71%) had one of the 41 most common DRGs. Predictive models were derived on
      a random subset of two thirds of the patients and were validated on the remaining
      third. The following patient data were obtained: admission and prior diagnostic
      test results, diagnoses, vital signs; demographic data; prior inpatient and
      outpatient visits; tests and treatments ordered within 24 hours of admission
      (discretionary data); DRGs; and total inpatient costs (estimated from charges).
      Diagnosis-related groups explained 24% of the variance in total costs in the
      derivation patient set and 16% in the validation set. When only nondiscretionary
      data were used, the models retained only clinical laboratory results and prior
      diagnoses, explaining 20% of the derivation set variance in total costs and 16%
      in the validation set. Adding DRGs increased the variance explained in the
      derivation set to 34%, but decreased to 24% in the validation set. Adding
      discretionary data substantially increased the explained variance in the
      derivation and validation patient sets. The models' median predicted costs
      underestimated true costs by 10% to 13%, with the lowest error in the models
      using all types of variables. Clinical data gathered during routine clinical care
      can be used to adjust for case mix and identify high-cost patients early in their
      hospital stays, when they could be targeted by cost-containment interventions.

PMID- 7823641
TI  - How consistent is patient-reported pre-admission health status when collected
      during and after hospital stay?

PMID- 7823642
TI  - Do home visits by nurses reduce day surgery cancellation rates? Results of a
      randomized controlled trial.

PMID- 7823643
TI  - Medicaid caps. Implications for ambulatory services in academic medical centers.

PMID- 7823644
TI  - Construction and validation of an alternate form general mental health scale for
      the Medical Outcomes Study Short-Form 36-Item Health Survey.
AB  - Alternate-form health measures are useful for clinical trials or health services
      research requiring repeated administrations over a short interval of time.
      Further, by using alternate-form methodology, they can be utilized to estimate
      score reliability. Data from the Medical Outcomes Study were used to evaluate
      five alternate forms of the Short-Form 36-Item Health Survey (SF-36) general
      mental health scale (MHI-5). Well-established psychometric criteria were used to
      select the best alternate form and to estimate the reliability of the MHI-5 using
      the alternate-form methodology. Although a considerable degree of comparability
      across the five alternate forms was observed for criteria pertaining to estimates
      of item-internal consistency and reliability, distributional characteristics of
      scales, tests of empirical validity, and score equivalence at the individual
      level, we recommend one alternate form that satisfied all evaluation criteria and
      did so better than any other alternate form. Using the alternate-form methodology
      of estimating reliability, results suggest that the internal-consistency method
      underestimates the reliability of the MHI-5 by 3%. The methodology presented here
      should prove useful to others interested in constructing and evaluating alternate
      forms, and the alternate form recommended here (MHI-5AF) should prove useful
      across many health status assessment applications.

PMID- 7823645
TI  - Workload, data gathering, and quality of community pharmacists' advice.

PMID- 7823646
TI  - Infants of Mexican immigrants. Health status of an emerging population.
AB  - Previous studies suggest that infants of Mexican immigrants have favorable birth
      outcomes despite their high socioeconomic risks. These favorable outcomes have
      been associated with a protective sociocultural orientation among immigrants. A
      sample of 708 infants of Mexican origin was assessed to determine whether such
      health advantages at birth are sustained at 8 to 16 months of age, or
      alternatively, whether their health deteriorates because of adverse socioeconomic
      conditions. A a cross-sectional survey was conducted in San Diego County to
      determine whether the child was healthy or ill (the latter indicating a history
      of serious infectious disease) and the factors associated with this outcome.
      Among infants born without serious medical problems, 74% remained healthy. For
      26% of the infants, their health status was eroded by social conditions. Factors
      associated with illness were large households, barriers to care, and maternal
      characteristics including smoking, pregnancy complications, and employment. Women
      born in Mexico who were newcomers to the United States and spoke Spanish
      exclusively were more likely than non-newcomers to have ill children. In this
      population, one fourth of Latino infants of immigrants were at high risk for
      serious infectious disease despite using preventive care.

PMID- 7823647
TI  - Health status and severity of illness as predictors of outcomes in primary care.
AB  - Two measures of health status and severity of illness were tested as indicators
      of patient case-mix to predict health-related outcomes in a rural primary care
      community health clinic, using a convenience sample of 413 ambulatory adults
      (mean age = 40.4 years: 58.6% women, and 47.2% black). At baseline; patients
      completed the Duke Health Profile, and providers completed the Duke Severity of
      Illness Checklist. During the 18-month follow-up study, patients experienced the
      following outcomes: at least one follow-up visit (74.3%), more than six visits
      (20.6%), at least one referral or hospital admission (17.3%), upper tertile
      severity scores (24.9%), and upper tertile office charges (24.9%). Baseline
      physical health, perceived health, and severity scores were statistically
      significantly predictive of all five outcomes. Predictive accuracy (i.e., area
      under the receiver operating characteristic curves) for outcome probabilities
      estimated from a case-mix model of physical health, severity, age, gender, and
      race was 72.3% for follow-up, 69.7% for frequent follow-up, 70.5% for referral
      and/or hospital stay, 65.7% for high follow-up severity of illness, and 67.6% for
      high follow-up charges. These data support health status and severity of illness
      as case-mix indicators and outcome predictors of follow-up utilization, severity
      of illness, and cost in the primary care setting.

PMID- 7823648
TI  - The role of the primary care physician in patients' adherence to antidepressant
      therapy.
AB  - In this study, the authors attempted to determine predictors of adherence to
      antidepressant therapy and to identify specific educational messages, side
      effects, and features of doctor-patient collaboration that influence adherence.
      Patients newly prescribed antidepressants for depression at a health maintenance
      organization were identified by using automated pharmacy data and medical records
      review. Patients (n = 155) were interviewed 1 and 4 months after starting
      antidepressant medication. Approximately 28% of patients stopped taking
      antidepressants during the first month of therapy, and 44% had stopped taking
      them by the third month of therapy. Patients who received the following five
      specific educational messages--1) take the medication daily; 2) antidepressants
      must be taken for 2 to 4 weeks for a noticeable effect; 3) continue to take
      medicine even if feeling better; 4) do not stop taking antidepressant without
      checking with the physician; and 5) specific instructions regarding what to do to
      resolve questions regarding antidepressants--were more likely to comply during
      the first month of antidepressant therapy. Asking about prior experience with
      antidepressants and discussions about scheduling pleasant activities also were
      related to early adherence. Side effects, only at severe levels, were associated
      with early noncompliance. Neuroticism, depression severity, and other patient
      characteristics did not predict adherence. Primary care physicians may be able to
      enhance adherence to antidepressant therapy by simple and specific educational
      messages easily integrated into primary care visits.

PMID- 7823649
TI  - Selecting disease-outcome pairs for monitoring the quality of hospital care.
AB  - Health care payors and providers are increasingly monitoring hospital discharge
      data bases for adverse events as markers for quality of care. The principal
      criticisms of these analyses have focused on the impediments to risk adjustment
      posed by the incompleteness and inaccuracy of the data bases. However, efforts to
      address the inadequacies of the data bases will not correct deficiencies of the
      analytic process. These deficiencies arise from the application of one adverse
      outcome to all disease states. Instead, analysis should be restricted to
      comparisons of subgroups of patients in which a close fit exists between the
      quality of care for the disease state and the expected outcome. Furthermore,
      these disease-outcome pairs should be minimally subject to measurement error. The
      authors present a conceptual framework for developing such meaningful disease
      outcome pairs, and using the hospital discharge data base of the Department of
      Veterans Affairs, show how the framework can be used to devise a monitoring
      strategy for re-admission.

PMID- 7823650
TI  - Geographic variation in utilization of cataract surgery.
AB  - Cataract surgery is the most frequently performed surgical procedure on Medicare
      beneficiaries, with an annual cost to the Medicare program of more than $3.4
      billion. In this study, the relationship between demographic, environmental, and
      provider-related factors, and the likelihood that cataract surgery will be
      performed on a Medicare beneficiary were assessed. The association between
      likelihood of cataract surgery and patient age, sex, race, income, and latitude
      of residence was examined, as was the association with the supply of
      ophthalmologists and optometrists in each region, and the allowed charge for
      cataract surgery and cost of practice in a region. This cross-sectional,
      population-based study used administrative data. Both regional models, using
      least-squares regression and person-based models, using logistic regression were
      employed. A random 5% sample of 1986 and 1987 Medicare beneficiaries, 65 years of
      age and older, were included in the study. Medicare beneficiaries who lacked
      continuous Part A and Part B coverage during 1986 and 1987, or who were enrolled
      in a health maintenance organization at any time during this 2-year period of
      observation were excluded from the study to make certain that complete
      utilization data were available for each individual. Rate of cataract surgery per
      1,000 Medicare beneficiaries in each Bureau of Economic Analysis Economic Area
      (BEAEA) and the likelihood of an individual with particular characteristics
      undergoing cataract surgery were determined in separate regression models. The
      mean annual rate of cataract surgery during 1986 and 1987 in the 181 BEAEAs was
      25.4 surgeries per 1,000 persons 65 years of age or older (standard deviation =
      6.2, coefficient of variation = 0.24). Both the regional model and the person
      based model detected an association between a higher rate of and personal
      likelihood of cataract surgery and female gender, more southerly latitude, higher
      concentration of optometrists per 1,000 Medicare beneficiaries, and higher
      allowed charge for cataract surgery, after adjusting for variation in practice
      expense. The person-based model additionally demonstrated that increased
      likelihood of undergoing cataract surgery was associated with increasing age from
      65 to 94 years, white race, and living in a zip-code area with mean income
      greater than $15,000. Neither analysis detected a statistically significant
      association between the concentration of ophthalmologists per 1,000 Medicare
      beneficiaries and the regional rate of, or an individual's likelihood of,
      cataract surgery. Compared with the geographic variation in provision of other
      surgical procedures, the variation in cataract surgery across large geographic
      areas observed in this analysis was relatively low.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7823651
TI  - Quality and accountability in practice. Measuring, managing and making it all
      work in a reformed health care system.

PMID- 7823652
TI  - Performance measures. How are they developed, validated, and used?

PMID- 7823653
TI  - How do purchasers develop and use performance measures?

PMID- 7823654
TI  - What information do consumers want and how will they use it?

PMID- 7823655
TI  - Where are we, how did we get here, where are we going?

PMID- 7823656
TI  - How will physicians respond?

PMID- 7823657
TI  - Health care reform and its implications for quality of care.

PMID- 7823658
TI  - Roundtable demonstration ... review of care given in private physician offices to
      Medicare beneficiaries.

PMID- 7823659
TI  - Roundtable demonstration ... defining "quality" medical care.

PMID- 7823660
TI  - Profiling and performance measures. What are the legal issues?

PMID- 7823661
TI  - Profiling and performance measures. What are the ethical issues?

PMID- 7823662
TI  - The role of ethics in quality and accountability initiatives.

PMID- 7823663
TI  - Creativity and psychopathology.

PMID- 7823664
TI  - Predicting schizophrenia.

PMID- 7823665
TI  - Work may be good medicine.

PMID- 7823666
TI  - Pelvic rhabdomyosarcoma: paying the price of bladder preservation.

PMID- 7823667
TI  - Vaginal birth after caesarean section.

PMID- 7823668
TI  - Intensification of treatment and survival in all children with lymphoblastic
      leukaemia: results of UK Medical Research Council trial UKALL X. Medical Research
      Council Working Party on Childhood Leukaemia.
AB  - The UK Medical Research Council trial MRC UKALL X was designed to investigate the
      benefit of one or two courses of additional intensification therapy in children
      with acute lymphoblastic leukaemia receiving standard treatment. From 1985 to
      1990 1612 children, comprising more than 90% of eligible cases in the UK, were
      treated with intensive induction therapy, central nervous system directed therapy
      with cranial irradiation and intrathecal methotrexate, and continuing treatment
      for 2 years. 1171 children were randomised to receive additional intensification
      therapy at 5 weeks, 20 weeks, both, or neither. At follow-up of at least 3 years
      disease-free survival for all children at 5 years was 62% (95% confidence
      interval [Cl] 60.0-64.4), a significant improvement over the 56% (53.0-59.6)
      found in the preceding MRC UKALL trial. The 5-year disease-free survival was 71%
      (65.5-76.1) for children randomised to two blocks of intensification therapy,
      this being significantly better than the 62% (56.6-68.0), 61% (55.7-67.1), and
      57% (50.9-62.7) rates for the groups randomised to one intensification block at 5
      weeks, one at 20 weeks, and no intensification, respectively. The benefits of
      intensification therapy were seen irrespective of clinical factors known to
      influence outcome such as age, sex, and initial leucocyte count. We conclude that
      the addition of two courses of intensification therapy has produced a 14%
      improvement in disease-free survival and an 11% improvement in overall survival
      for the randomised patients. This additional treatment is of benefit to all
      children with acute lymphoblastic leukaemia, even those traditionally deemed at
      lower risk of relapse.

PMID- 7823669
TI  - Role of clotting factor VIII in effect of von Willebrand factor on occurrence of
      deep-vein thrombosis.
AB  - To elucidate the roles of the ABO blood group, von Willebrand factor (vWF), and
      clotting factor VIII in the process of deep-vein thrombosis we undertook a
      population-based patient-control study in which 301 consecutive patients younger
      than 70 with a first, objectively diagnosed episode of venous thrombosis and
      without an underlying malignant disorder were compared with 301 healthy controls
      matched for age and sex. In univariate analysis, blood group, vWF concentration,
      and factor VIII concentrations were all related to deep-vein thrombosis. The risk
      of thrombosis increased with increasing vWF or factor VIII concentration and was
      higher in subjects of non-O blood groups than in those of group O. In
      multivariate analysis only factor VIII remained as a risk factor, and the dose
      response relation between factor VIII concentration and risk of thrombosis
      persisted (subjects with factor VIII concentrations above 1500 IU/L had an
      adjusted odds ratio of 4.8 [95% Cl 2.3-10.0]). By contrast, the adjusted odds
      ratio for each vWF stratum did not differ from 1, and that for blood group was
      1.5 (1.0-2.2). Our findings point to an effect on thrombosis risk of vWF and
      blood group, the former fully and the latter at least partly mediated through
      factor VIII. The 25% prevalence of factor VIII concentrations above 1500 IU/L
      among unselected consecutive thrombosis patients and the high adjusted relative
      risk for thrombosis lead to the conclusion that high factor VIII concentrations
      are common and represent a clear increase in risk of thrombosis, similar to the
      risks conferred by deficiencies of the coagulation-inhibiting proteins and
      activated protein C resistance.

PMID- 7823671
TI  - Haemoglobin-based blood substitutes and sepsis.
AB  - An important concern that has received little attention is the possible increased
      susceptibility to bacterial infections of patients infused with cell-free
      haemoglobin-based blood substitutes. We show that pyridoxalated polymerised human
      haemoglobin promotes fulminating Escherichia coli septicaemia in mice, which
      draws attention to the potential danger of such products in the clinic.

PMID- 7823670
TI  - Impact of face-washing on trachoma in Kongwa, Tanzania.
AB  - Observational studies have suggested that the prevalence of trachoma is lower in
      children with clean faces than in those with ocular or nasal discharge or flies
      on the face. We carried out a community-based randomised trial in three pairs of
      villages to assess the impact on trachoma of a face-washing intervention
      programme following a mass topical antibiotic treatment campaign. Six villages in
      Kongwa, Tanzania, were randomly assigned mass treatment plus the face-washing
      programme or treatment only. 1417 children aged 1-7 years in these villages were
      randomly selected and followed up for trachoma status and observations of facial
      cleanliness at baseline and 2, 6, and 12 months. At 12 months, children in the
      intervention villages were 60% more likely to have had clean faces at two or more
      follow-up visits than children in the control villages. The odds of having severe
      trachoma in the intervention villages were 0.62 (95% Cl 0.40-0.97) compared with
      control villages. A clean face at two or more follow-up visits was protective for
      any trachoma (odds ratio 0.58 [0.47-0.72]) and severe trachoma (0.35 [0.21
      0.59]). This community-based participatory approach to face-washing intervention
      had variable penetration rates in the villages and was labour intensive. However,
      we found that, combined with topical treatment, community-based strategies for
      improving hygiene in children in trachoma-endemic villages can reduce the
      prevalence of trachoma.

PMID- 7823672
TI  - Capsaicin and the cause of causalgia.
AB  - From self-experimentation, I propose that the pain which occurs after application
      of capsaicin is causalgia and that this "capsaicin causalgia" is due to actual or
      functional depletion of neuropeptides such as substance P. This idea could
      provide an objective definition of the causalgic syndromes and improve the means
      of diagnosis. The analogy with capsaicin causalgia could also be extended to the
      pain of epidermal necrolysis, solar and thermal burns, and leprosy. The concept
      could lead to a better treatment of these causalgic syndromes by modulation of
      neuropeptide concentration or responsivity, or by mitigation of the consequences
      of its depletion.

PMID- 7823673
TI  - Gene analysis of L1 neural cell adhesion molecule in prenatal diagnosis of
      hydrocephalus.
AB  - X-linked hydrocephalus is the most common form of inherited hydrocephalus, and is
      associated with severe neurological deficits and premature death. We have shown
      that mutations in the gene encoding L1 neural cell adhesion molecule result in X
      linked hydrocephalus, which enables improved prenatal diagnosis and investigation
      of the role of this molecule in sporadic cases. Here we report two pedigrees with
      apparently sporadic hydrocephalus in which we demonstrated a disabling mutation
      in the L1 gene. This enabled us to provide definitive prenatal diagnosis at 10
      weeks' gestation.

PMID- 7823674
TI  - Acute liver failure.

PMID- 7823675
TI  - Vitamin E.

PMID- 7823676
TI  - How to achieve a Wellcome brain gain.

PMID- 7823677
TI  - Clinical aspects of psychoneuroimmunology.

PMID- 7823678
TI  - Incidence and risk factors of post-traumatic epilepsy in childhood.

PMID- 7823679
TI  - Kala azar in eastern Upper Nile Province, southern Sudan.

PMID- 7823680
TI  - Botulinum toxin in therapy of anal fissure.

PMID- 7823681
TI  - Mitochondrial DNA mutations and survival rate.

PMID- 7823682
TI  - Hepatitis C virus.

PMID- 7823683
TI  - Hepatitis C virus.

PMID- 7823684
TI  - Interaction of triazolam and ketoconazole.

PMID- 7823685
TI  - Diagnosis of aortic dissection by immunoassay for circulating smooth muscle
      myosin.

PMID- 7823686
TI  - Helicobacter pylori reinfection and rapid relapse of low-grade B-cell gastric
      lymphoma.

PMID- 7823687
TI  - Breastfeeding.

PMID- 7823688
TI  - Breastfeeding.

PMID- 7823689
TI  - Breastfeeding.

PMID- 7823690
TI  - Use of surgical instruments in Creutzfeldt-Jacob disease.

PMID- 7823691
TI  - Coroners and public health.

PMID- 7823693
TI  - Restriction orders and the UK Home Office.

PMID- 7823692
TI  - Living wills in HIV infection and AIDS.

PMID- 7823694
TI  - Effect of liver transplantation on autonomic dysfunction in familial amyloidotic
      polyneuropathy type I.

PMID- 7823695
TI  - Chronic urticaria and Toxocara canis.

PMID- 7823696
TI  - Does hormone replacement therapy cause dependence?

PMID- 7823697
TI  - HPV-16 transmission.

PMID- 7823698
TI  - Coronary angiography in migraine patient after subcutaneous sumatriptan.

PMID- 7823699
TI  - Transplantation of porcine fetal pancreas to diabetic patients.

PMID- 7823700
TI  - Haemopoietic growth factor GM-CSF for aplastic anaemia in children.

PMID- 7823701
TI  - Is it time to consider domiciliary nitric oxide?

PMID- 7823702
TI  - Congenital bilateral absence of vas deferens in absence of cystic fibrosis.

PMID- 7823703
TI  - Secondary amenorrhoea due to persistent corpus luteum in brucellosis.

PMID- 7823704
TI  - Complication of dobutamine stress echocardiography.

PMID- 7823705
TI  - Auscultation for mitral valve prolapse.

PMID- 7823706
TI  - Somatic mosaicism and clinical variation in tuberous sclerosis complex.

PMID- 7823707
TI  - Fortress WHO: breaching the ramparts for health's sake.

PMID- 7823708
TI  - Preventing nosocomial transmission of tuberculosis.

PMID- 7823709
TI  - Population breast cancer screening: theory, practice, and service implications.

PMID- 7823710
TI  - Non-invasive tests for Chlamydia trachomatis.

PMID- 7823711
TI  - Debugging computer-assisted antibiotic prescribing.

PMID- 7823712
TI  - Risk of stroke in the distribution of an asymptomatic carotid artery. The
      European Carotid Surgery Trialists Collaborative Group.
AB  - Screening and carotid endarterectomy have been advocated for asymptomatic carotid
      stenosis. However, the risk of stroke without treatment has not been adequately
      defined. We investigated the risk of stroke in the distribution of the
      asymptomatic carotid artery in 2295 patients randomised in the European Carotid
      Surgery Trial. During a mean follow-up of 4.5 years, there were 69 carotid
      territory strokes, nine of which were fatal, giving three year Kaplan-Meier risks
      of stroke and fatal stroke of 2.1% (95% Cl, 1.5-2.8) and 0.3% (95% Cl, 0.06-0.56)
      respectively. The stroke risk in the 127 patients with severe (70-99%) carotid
      stenosis was 5.7% (95% Cl, 1.5-9.8). Given these low stroke risks, the potential
      benefit of endarterectomy for asymptomatic carotid stenosis is small. Population
      screening is not justified and endarterectomy for asymptomatic carotid stenosis
      should only be performed in the context of well organised randomised controlled
      trials.

PMID- 7823713
TI  - Diagnosis of Chlamydia trachomatis genitourinary infection in women by ligase
      chain reaction assay of urine.
AB  - Genitourinary infection with Chlamydia trachomatis is a common and potentially
      serious sexually transmitted disease. Diagnosis of C trachomatis infection in
      women typically relies on culture of endocervical swabs, an invasive and
      expensive procedure. The ligase chain reaction (LCR) is an in-vitro nucleic acid
      amplification technique that exponentially amplifies selected DNA sequences. We
      have compared an LCR-based assay to detect C trachomatis plasmid DNA in first
      void urine with culture of endocervical swabs for matched specimens from 1937
      women from four geographic regions. Discordant specimen pairs were further tested
      by direct fluorescent antibody staining for elementary bodies and an alternative
      LCR assay based on the chlamydial outer membrane protein gene. An "expanded gold
      standard" was defined to include all culture-positive as well as culture
      negative, confirmed LCR-positive women. The sensitivity and specificity of the
      LCR assay with first void urine samples compared with the expanded gold standard
      were 93.8% and 99.9%, respectively; the corresponding values for culture were
      65.0% and 100%, respectively. Thus, an automated LCR assay of readily obtained
      urine samples showed a detection rate for infected women almost 30% greater than
      that of endocervical swab culture. The LCR assay was highly effective for the
      detection of C trachomatis in urine from women with or without signs or symptoms
      of chlamydial genitourinary tract infection.

PMID- 7823714
TI  - Relation of exposure to airway irritants in infancy to prevalence of bronchial
      hyper-responsiveness in schoolchildren.
AB  - To find out whether exposure to sulphur dioxide during infancy is related to the
      prevalence of bronchial hyper-responsiveness (BHR), we studied schoolchildren
      (aged 7-13 years) from two areas of Norway--a valley containing a sulphur-dioxide
      emitting aluminium smelter and a similar but non-industrialised valley. Bronchial
      responsiveness was assessed in 529 of the 620 participants. The median exposures
      to sulphur dioxide and fluoride were 37.1 micrograms/m3 and 4.4 micrograms/m3 at
      ages 0-12 months and 37.9 micrograms/m3 and 4.4 micrograms/m3 at 13-36 months.
      The risk of BHR increased with exposure to sulphur dioxide and fluoride at these
      ages; the odds ratio for a 10 micrograms/m3 increase in sulphur dioxide exposure
      at 0-12 months was 1.62 (95% CI 1.11-2.35) and that for a 1 microgram/m3 increase
      in fluoride exposure was 1.35 (1.07-1.70) at 0-12 months and 1.38 (1.05-1.82) at
      13-36 months. Exposure to these low concentrations of airway irritants during
      early childhood is associated with an increased prevalence of BHR in
      schoolchildren.

PMID- 7823715
TI  - alpha 1-Antitrypsin therapy in a case of thrombotic thrombocytopenic purpura.
AB  - In thrombotic thrombocytopenic purpura (TTP), activated leucocytes release
      elastase which mobilises unusually large von Willebrand factor (vWF) multimers
      from the endothelium. We investigated the effect of an inhibitor of leucocyte
      elastase (alpha 1-antitrypsin) on circulating vWF and platelet count in a patient
      with chronic relapsing TTP. alpha 1-antitrypsin consistently normalised vWF
      multimeric composition but failed to increase platelet count and induce
      remission. Plasma cryosupernatant, which never normalised vWF, always induced
      laboratory and clinical remission within 96 hours. In chronic relapsing TTP,
      unusually large vWF multimers are not the main cause of intravascular platelet
      aggregation.

PMID- 7823716
TI  - Patterns of abuse in Sikh asylum-seekers.
AB  - Many states practise or condone torture to control dissident groups in their
      population. Most techniques used and the resulting injuries are common to all
      cultures. 31 male Sikh asylum-seekers, examined between December, 1991, and May,
      1994, showed a pattern of abuse that included features particular to their region
      of origin. All gave a persuasive history of serious abuse and all showed long
      term mental and physical effects that could be convincingly attributed to their
      experiences.

PMID- 7823717
TI  - Alcoholic liver disease.

PMID- 7823718
TI  - Vitamin K.

PMID- 7823720
TI  - Vows of cuts and glimmers of hope.

PMID- 7823719
TI  - Control of nosocomial transmission of multidrug-resistant Mycobacterium
      tuberculosis among healthcare workers and HIV-infected patients.
AB  - From 1988 to 1990, an outbreak of multidrug-resistant tuberculosis (MDR-TB) among
      patients, and an increased number of tuberculin-skin-test conversions among
      healthcare workers, occurred on the HIV ward of Jackson Memorial Hospital, Miami,
      Florida, USA. Measures similar to those subsequently recommended in the 1990
      Centers for Disease Control and Prevention guidelines were implemented on the HIV
      ward by June, 1990, and in September, 1992, we evaluated the efficacy of these
      control measures. Among MDR-TB patients and healthcare workers with tuberculin
      skin-test conversions on the HIV ward, we looked for evidence of exposure to HIV
      ward MDR-TB patients positive for acid-fast bacilli in sputum during initial
      (January-May, 1990) and follow-up (June, 1990-June, 1992) periods. Exposure
      before implementation of control measures to an infectious MDR-TB patient on the
      HIV ward was recorded in 12 of 15 (80%) MDR-TB patients during the initial period
      and 5 of 11 (45%) MDR-TB patients during follow-up. After implementation of
      control measures, no episodes of MDR-TB could be traced to contact with
      infectious MDR-TB patients on the HIV ward. Skin-test conversions among workers
      on the HIV ward declined from 7 of 25 (28%) during the initial period to 3 of 17
      (18%) in the early (June, 1990-February, 1991) and 0 of 23 in the late (March,
      1991-June, 1992) follow-up periods (p < 0.01). Skin-test conversions among
      healthcare workers were not associated with increased exposure to MDR-TB
      patients, and were not significantly higher among workers on the HIV ward than on
      a control ward without tuberculosis patients (3/27 vs 0/16). These data
      demonstrate that implementation of measures similar to the Centers for Disease
      Control and Prevention 1990 tuberculosis-control guidelines were effective in
      halting transmission of MDR-TB to healthcare workers and HIV-infected patients.

PMID- 7823721
TI  - Mental spring cleaning after Kobe.

PMID- 7823722
TI  - Lowering the US hurdles for AIDS drugs.

PMID- 7823723
TI  - Screening blood.

PMID- 7823724
TI  - Is the evidence for homoeopathy reproducible?

PMID- 7823725
TI  - Is the evidence for homoeopathy reproducible?

PMID- 7823726
TI  - Is the evidence for homoeopathy reproducible?

PMID- 7823727
TI  - Is the evidence for homoeopathy reproducible?

PMID- 7823728
TI  - Is the evidence for homoeopathy reproducible?

PMID- 7823729
TI  - Cancer mortality and low doses of ionising radiation.

PMID- 7823730
TI  - Electric shock to paramedic during cardiopulmonary resuscitation of patient with
      implanted cardiodefibrillator.

PMID- 7823731
TI  - Gynaecological monitoring during tamoxifen therapy.

PMID- 7823732
TI  - Lack of induction of endometrial hyperplasia with tamoxifen.

PMID- 7823733
TI  - Treatment of genital chlamydial infection.

PMID- 7823734
TI  - Eliciting P300 in comatose patients.

PMID- 7823735
TI  - Dietary polyunsaturated fatty acids and aortic plaques.

PMID- 7823736
TI  - Dietary polyunsaturated fatty acids and aortic plaques.

PMID- 7823737
TI  - Dietary polyunsaturated fatty acids and aortic plaques.

PMID- 7823738
TI  - Plague in India.

PMID- 7823739
TI  - Plague in India.

PMID- 7823740
TI  - Kernohan's notch and misdiagnosis.

PMID- 7823741
TI  - Eschewing the predictable.

PMID- 7823742
TI  - Ethics of executed person on Internet.

PMID- 7823743
TI  - Evening primrose oil and atopic eczema.

PMID- 7823744
TI  - Acute hepatitis B infection after vaccination.

PMID- 7823745
TI  - Acute hepatitis B infection after vaccination.

PMID- 7823746
TI  - Acute hepatitis B infection after vaccination.

PMID- 7823747
TI  - Acute hepatitis B infection after vaccination.

PMID- 7823748
TI  - Is Huntington's disease of cerebellar/brainstem origin?

PMID- 7823749
TI  - Validity of the 4S simvastatin trial.

PMID- 7823750
TI  - Regimen containing short-term rifampicin for pulmonary tuberculosis in HIV
      infection.

PMID- 7823751
TI  - Rifabutin prophylaxis against Mycobacterium avium complex infection.

PMID- 7823752
TI  - Stilboestrol exposure in utero and risk of pre-eclampsia.

PMID- 7823753
TI  - Hippocampal volume losses in minimally impaired elderly.

PMID- 7823754
TI  - Comparative effects of exogenous nitrovasodilators on cGMP levels in different
      canine blood vessels.
AB  - Nitrovasodilators, by releasing nitric oxide (NO) in vascular smooth muscle,
      activate soluble guanylate cyclase (sGC) in vascular smooth muscle. However,
      there is little information on their relative effectiveness, concentration
      ranges, or on the incubation times required to produce maximum sGC stimulation.
      To determine the optimal concentrations and incubation times we measured 3', 5'
      cyclic guanosine monophosphate (cGMP) levels in response to different
      concentrations of NO, S-nitroso-L-cysteine (SNC), and S-nitroso-N
      acetylpenicillamine (SNAP), in canine aorta, femoral, and carotid arteries
      incubated in Krebs. Production of cGMP following incubation of endothelium
      denuded tissues with NO, SNC, and SNAP peaked close to 20 +/- 5, 90 +/- 20, and
      120 +/- 60 seconds respectively. Results indicate that cGMP levels vary with
      concentration of nitrovasodilators and time of incubation. SNAP was the least
      effective in increasing cGMP levels among the three nitrovasodilators used. In
      different vascular beds, the production of cGMP in the presence of
      nitrovasodilators may depend on variations in the levels of guanylate
      triphosphate (GTP) and/or sGC.

PMID- 7823755
TI  - NE-100, a novel sigma ligand: effects on [3H]TCP binding to intact primary
      cultured neuronal cells.
AB  - N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]-ethylamine monohydrochloride
      (NE-100), a potent and highly selective sigma ligand, haloperidol,
      (+)pentazocine, 1-(cyclopropyl-methyl)-4-(2'-(4"-fluorophenyl)-2'-oxoethyl)
      piperidine HBr (DuP 734) and 4-(2'-(4"-cyanophenyl)-2'-oxoethyl) 1
      (cyclopropylmethyl)piperidine (XJ 448) inhibited carbachol-induced inositol 1,4,5
      triphosphate (IP3) formation in a dose-dependent manner. The rank order of
      potency of the tested drugs for inhibition was: haloperidol > or = (+)pentazocine
      = NE-100 > DuP 734 = XJ 448. In addition, the effects of NE-100, DuP 734 and XJ
      448 upon [3H]TCP binding were examined using primary cultured neuronal cells
      derived from the fetal rat telencephalon. These drugs inhibited [3H]TCP binding
      to intact cells. The ability of the test drugs to inhibit [3H]TCP binding to
      primary cultured neuronal cells was in the order: NE-100 > DuP 734 > XJ 448.
      These observations suggest that NE-100 indirectly modulates the N-methyl-D
      aspartate (NMDA)/phencyclidine (PCP) receptor ion channel complex (NMDA receptor
      ion channel), presumably through sigma-1 sites.

PMID- 7823756
TI  - The mu1, mu2, delta, kappa opioid receptor binding profiles of methadone
      stereoisomers and morphine.
AB  - The binding affinities of racemic methadone and its optical isomers R-methadone
      and S-methadone were evaluated for the opioid receptors mu1, mu2, delta and
      kappa, in comparison with that of morphine. The analgesic R-methadone had a 10
      fold higher affinity for mu1 receptors than S-methadone (IC50 3.0 nM and 26.4 nM,
      respectively). At the mu2 receptor, the IC50 value of R-methadone was 6.9 nM and
      88 nM for S-methadone, respectively. As expected, R-methadone had twice the
      affinity for mu1 and mu2 receptors than the racemate. All of the compounds tested
      had low affinity for the delta and kappa receptors. This result suggests that S
      methadone does not essentially contribute to opioid effect of racemic methadone.
      R-methadone has a receptor binding profile which resembles that of morphine.

PMID- 7823757
TI  - Ibudilast, an anti-allergic and cerebral vasodilator, modulates superoxide
      production in human neutrophils.
AB  - We evaluated the effect of ibudilast on superoxide generation in human
      neutrophils by chemiluminescence development using luciferine analog, FCLA. By
      incubating neutrophils with ibudilast (2-200 microM) for more than 10 minutes,
      fMLP- or PMA-induced chemiluminescence was enhanced. However, the fMLP-induced
      chemiluminescence was suppressed by incubation for less than 10 minutes. This
      suppressed effect was missing with PMA-induced chemiluminescence. On the both
      fMLP- and PMA-induced chemiluminescence, the priming effect of ibudilast was
      further enhanced by the treatment with H-7, a protein kinase C inhibitor. In
      contrast, the priming effect of ibudilast on the fMLP-induced chemiluminescence
      was abolished by the treatment with ST-638, a selective inhibitor of tyrosine
      kinase. Ibudilast showed a transient stimulatory effect on cyclic AMP
      accumulation which continued for only a few minutes. Ibudilast showed no
      significant effect on phospholipase D dependent chemiluminescence, 1,4,5
      trisphosphate level, or protein kinase C activity. Ibudilast inhibited
      extracellular calcium influx. These results suggest that ibudilast acts on or
      through tyrosine kinase to achieved its priming effect on the fMLP-induced
      chemiluminescence. The early and transient increase in cyclic AMP level may
      explain the inhibitory effect of ibudilast on the fMLP-induced chemiluminescence
      after short time of incubation.

PMID- 7823758
TI  - Inhibition of colchicine absorption by the fat substitutes, sucrose polyester and
      tricarballylate triester, in the rat.
AB  - The effect of non-absorbable fat substitutes (sucrose polyester (SPE) and
      tricarballylate triester (TCTE)) on the enterohepatic circulation of colchicine
      was studied in the rat. In a first experiment, emulsions of either sunflower oil
      (SFO), SPE, or TCTE, were introduced into the ligated small intestine and
      compared to a control group receiving physiological saline. All the groups
      received colchicine as an intravenous bolus. The plasma levels of colchicine in
      all groups was not affected, and luminal samples indicated that SPE and TCTE have
      no influence on the biliary excretion of colchicine (a previous experiment in
      bile duct-cannulated rats showed that SPE and TCTE, introduced by intragastric
      tube, have no effect on bile flow rate). In a second experiment, colchicine
      diluted in bile was mixed with saline or emulsions of either SFO, SPE or TCTE,
      and introduced into the ligated small intestine. The area under the curve and the
      maximal plasma concentration of colchicine were reduced when the drug was mixed
      with SPE or TCTE rather than saline (p < 0.0005). After 150 min, luminal samples
      were taken and showed significantly higher (p < 0.034) concentrations of
      colchicine in both SPE and TCTE groups compared to the saline group, indicating a
      significant inhibition of reabsorption of biliary colchicine. In conclusion, the
      non-absorbable fat substitutes, SPE and TCTE, did not influence biliary excretion
      of colchicine but reduced its reabsorption, thus altering its enterohepatic
      circulation.

PMID- 7823759
TI  - The role of calcium in the hydrolysis of the organophosphate paraoxon by human
      serum A-esterase.
AB  - Human serum A-esterase is a calcium-dependent enzyme that hydrolyzes the
      organophosphate paraoxon by an Ordered Uni Bi kinetic mechanism. Incubation of
      various concentrations of calcium chloride with human serum A-esterase resulted
      in corresponding changes in appk3 and appE for the reaction, while appk2 was
      unaffected. Carboxyglutamic acid (CAG) prevented calcium chloride from altering
      appk3, but not appE. Similarly CAG reduced the calcium-stimulated nonenzymatic
      hydrolysis of paraoxon, as well as the calcium-stimulated de-phosphorylation of
      chymotrypsin phosphorylated by paraoxon. These results suggest that calcium plays
      two roles in the hydrolysis of paraoxon by A-esterase. Firstly, calcium is
      required in order to maintain an active site. In this capacity calcium might
      participate directly in the catalytic reaction, or it might be required in order
      to maintain the appropriate confirmation of the active site. And secondly, free
      calcium (or calcium weakly associated with A-esterase) facilitates the removal of
      diethyl phosphate from A-esterase, probably by polarizing the P = O bond of the
      diethyl phosphate-A-esterase intermediate, thereby rendering phosphorus more
      susceptible to nucleophilic attack by hydroxide ions.

PMID- 7823760
TI  - Effects of pituitary adenylate-cyclase activating peptide (PACAP) on the rat
      adrenal secretory activity: preliminary in-vitro studies.
AB  - PACAP did not affect secretory activity of dispersed rat adrenocortical cells,
      but it markedly raised aldosterone (ALDO) and corticosterone (B) production by
      adrenal slices, containing both medullary and cortical tissues. The secretagogue
      effects of PACAP were suppressed by PACAP(6-38), a specific competitive
      antagonist. Isoprenaline (IP) enhanced ALDO, but not B secretion of adrenal
      slices, and l-alprenolol (AL) completely blocked IP effect. AL and corticotropin
      inhibiting peptide (CIP) partially reversed ALDO response to a maximal effective
      concentration of PACAP; AL did not affect B response to a maximal effective
      concentration of PACAP, while CIP completely annulled it. Quarters of regenerated
      adrenocortical autotransplants, that are completely deprived of chromaffin cells,
      though displaying ALDO and B responses to IP and ACTH, were insensitive to PACAP.
      The hypothesis is advanced that adrenal medulla plays a pivotal role in the
      mechanism(s) underlying the adrenocortical secretagogue action of PACAP, being
      mineralocorticoid and glucocorticoid responses probably mediated by the release
      by chromaffin cells of catecholamine and ACTH or exclusively ACTH, respectively.

PMID- 7823761
TI  - Alpha 2-adrenoceptors vs. imidazoline receptors: implications for alpha 2
      mediated analgesia and other non-cardiovascular therapeutic uses.
AB  - The multiple clinical actions of clonidine have historically been linked to the
      same receptor (alpha 2-adrenoceptor) due to the belief that clonidine was a
      selective alpha 2-agonist. However, it is now recognized that clonidine binds
      with a similar affinity to alpha 2-adrenoceptors and to non-adrenergic
      imidazoline receptors. These two pharmacological targets (and subtypes of each
      alpha 2 and imidazoline receptors) provide the basis for a possible separation of
      cardiovascular and other targeted effects, such as analgesia. Consequently, the
      design of selective alpha 2-adrenoceptor (subtype) agonists as analgesics devoid
      of the cardiovascular effects associated with clonidine appears to be a rational
      approach to novel therapeutic agents. The present review focuses on alpha 2
      adrenoceptor subtype/imidazoline diversity as a target for analgesic (and other
      CNS) drug discovery.

PMID- 7823762
TI  - Potent protective effect of melatonin on in vivo paraquat-induced oxidative
      damage in rats.
AB  - The in vivo effect of melatonin on paraquat-induced oxidative damage in rat lung
      and liver was studied using two parameters: the concentration of malonaldehyde
      and 4-hydroxyalkenals as indices of lipid peroxidation; changes in total and
      oxidized glutathione. Melatonin (10 mg/kg) or an equal volume of saline were
      administered intraperitoneally (ip) to rats 30 min prior to an ip injection of
      paraquat (20 mg/kg or 70 mg/kg). After paraquat treatment, the animals received
      melatonin or saline ip injections every six hours for 24 hours. Rats were killed
      24 hours after paraquat injection. In lung, both the low and high dose of
      paraquat, when administered with saline, augmented lipid peroxidation (100% and
      18%, respectively) above levels found in control animals. Treatment with
      melatonin completely reversed this effect. In liver, paraquat (70 mg/kg)
      increased lipid peroxidation by 40% over the levels of control animals. The
      increase was completely abolished by treatment with melatonin. Paraquat at 20
      mg/kg did not induce any significant change in liver lipid peroxidation. Paraquat
      treatment resulted in a significant decrease of total glutathione concentration
      and increased oxidized glutathione in both lung and liver. These effects were
      abolished by treatment with melatonin. The results suggest that melatonin confers
      marked protection against paraquat-induced oxidative toxicity in both the lung
      and liver.

PMID- 7823764
TI  - Acute toxicity and depression of phagocytosis in vivo by liposomes: influence of
      lysophosphatidylcholine.
AB  - Small unilamellar phospholipid vesicles (liposomes), intended as drug carriers,
      have recently been demonstrated to reversibly depress phagocytic activity in rats
      when injected in a single high dose (2g of lipid per kg body weight) as revealed
      by the carbon clearance test. Depression of the phagocytic function was found to
      vary widely depending on the lipid used [M. Brandl et al., Pharm. Pharmacol.
      Lett., 4 (1) 1-4, 1994]. This study has now been extended in two directions:
      Firstly, liposomes made of the same type of lipid but different batches of raw
      material were compared in terms of their influence on phagocytosis as well as for
      their contents of impurities. The test revealed great variability of RES
      suppression between different batches of hydrogenated soy PC, whereas the
      reproducibility of the carbon clearance test was satisfactory with liposomes made
      of a single batch of raw material. Thin layer chromatographic analyses of the
      used phosphatidylcholines (PCs) and limulus tests on lipopolysaccharides revealed
      lysophosphatidylcholine (lysoPC) as the only impurity which showed parallels with
      the observed differences in phagocytosis. Secondly by "spiking"
      phosphatidylcholine with increasing amounts of lysoPC the latter could be proven
      to enhance RES depression by liposomes in a dose-dependent manner. At the same
      time a strong and dose-limiting increase in acute toxicity of PC vesicles was
      observed with increasing contents of lysoPC. However, in cholesterol-containing
      vesicles lysoPC-spiking did not significantly alter their behaviour, for lysoPC
      contents of up to 10%. Only PC/cholesterol-vesicles containing lysoPC contents as
      high as 15% provoked enhanced RES depression and toxicity compared to lysoPC-free
      vesicles. LysoPC and cholesterol in liposomes are known to play a destabilizing
      and stabilizing role respectively within liposomal bilayers which might influence
      recognition and uptake of vesicles by macrophages and thus modulation of
      phagocytosis.

PMID- 7823763
TI  - Effect of lipopolysaccharide on the physical conformation of the erythrocyte
      cytoskeletal proteins.
AB  - Red blood cell deformability is important for effective circulation in the
      capillaries. It is known that red cell deformability is significantly reduced
      during septic shock. Surface to volume ratio, physical effects of the
      cytoskeletal proteins and the fluidity of lipid bilayer are some of the important
      intrinsic factors that regulate this mechanical function. Alterations in the
      physical conformation of cytoskeletal proteins in septic conditions could
      significantly alter their function. In this study, erythrocytes in whole blood
      were treated with lipopolysaccharide, the outer covering of Gram-negative
      bacteria released during Gram-negative sepsis. Electron paramagnetic resonance
      spectroscopy in conjunction with a protein-specific maleimide nitroxide spin
      label covalently bound to cytoskeletal proteins was used to investigate the
      resulting changes occurring in the physical state of cytoskeletal proteins in
      isolated membranes. Treatment of red blood cells with a lipopolysaccharide
      concentration as low as 40 micrograms/mL of blood solution for 90 minutes showed
      a significant decrease in the relevant EPR parameter (p < 0.01) of the spin label
      bound to subsequently isolated membranes, suggestive of a decreased segmental
      motion of the spin label and an increase in cytoskeletal protein-protein
      interactions. These results suggest a marked conformational alteration in the
      cytoskeletal proteins induced by the lipopolysaccharide and may explain, in part,
      the marked reduction in red blood cell deformability during septic shock.
      Bacterial lipopolysaccharide does not exert most of its effects on the host
      directly, but rather elicits the production of host factors that leads to complex
      septic shock. Leukocytes, endothelial tissue and many other cells release these
      mediators. Leukocytes are thought to be a particularly important source of such
      mediators, including cytokines (tumor necrosis factor, interleukins, etc.),
      oxygen free radicals, proteases, and hydrolyses. In order to characterize the
      possible mechanism by which the lipopolysaccharide acts on the physical state of
      the erythrocyte cytoskeleton, erythrocytes void of leukocytes and plasma were
      treated with lipopolysaccharide. The relevant EPR parameter showed no significant
      change over the control value. These results indicate that the leukocytes and
      their factors are responsible for the rearrangements seen in the cytoskeletal
      proteins of the erythrocyte membrane.

PMID- 7823765
TI  - Current and historical mortality from cancer and cardiovascular disease in
      relation to age: U.S. and world values.
AB  - Data from the World Health Organization, U.S. Vital Statistics, the Historical
      Abstracts of the United States and the census of the United States were used to
      compare current world and states data on cancer death rate and age with
      historical data that shows the changing percentage of elderly. Current annual
      death rates from malignant neoplastic disease among the 73 countries for which
      data exist are highly correlated with the percent of the population > or = 60 yrs
      of age and a virtually identical relation exists presently among the 50 states of
      the U.S. The current world and states data provide a remarkably accurate snapshot
      of U.S. cancer death rates over the past century during which time the U.S.
      elderly population increased substantially. Data on U.S. lung cancer death rates
      since 1940 were similarly examined and these historical numbers also show good
      agreement with current values among countries that today span the same proportion
      of elderly that the U.S. had over this period. The agreement of current and
      historical CA death rate and age contrasts sharply with the picture that emerges
      when cardiovascular death rates and death rate from all causes are examined. The
      geographic and time invariance seen in the cancer data seems inconsistent with
      identical exposure to carcinogens and suggests that biological aging is an
      important intrinsic factor in cancer.

PMID- 7823766
TI  - Comparative effects of adrenomedullin, an adrenomedullin analog, and CGRP in the
      pulmonary vascular bed of the cat and rat.
AB  - Responses to synthetic human adrenomedullin (ADM), a novel hypotensive peptide
      initially isolated from human pheochromocytoma cells, an ADM analog (ADM15-52),
      and a structurally related peptide, calcitonin gene-related peptide (CGRP), were
      compared in the pulmonary vascular bed of the cat and rat under constant flow
      conditions. When tone was increased with U46619, intraarterial injections of ADM
      (0.03-0.3 nmol), ADM15-52 (0.03-0.3 nmol), and of CGRP (0.03-0.3 nmol) caused
      dose-related decreases in pulmonary arterial perfusion pressure. When the
      relative vasodilator activity of the peptides was compared on a nmol basis, ADM
      was approximately 10-fold more potent in the cat than in the rat, whereas
      vasodilator responses to CGRP were very similar in both species. CGRP was
      slightly more potent than ADM in the rat, whereas ADM was slightly more potent
      than CGRP in the cat. ADM and ADM15-52 had similar pulmonary vasodilator activity
      in the cat, whereas the full sequence peptide was slightly more potent than ADM15
      52 in the rat. The present data demonstrate that ADM has significant vasodilator
      activity in the pulmonary vascular beds of the cat and of the rat, and that the
      relative potency of the vasodilator effects of ADM and ADM15-52 are different in
      the two species.

PMID- 7823767
TI  - Antagonism of nicotine's action by cocaine analogs.
AB  - Structure-activity relationships of a number of synthetic cocaine analogs are
      described comparing their effectiveness in antagonizing the behavioral effects of
      nicotine in mice with their ability to compete for [3H]mecamylamine,
      [3H]nicotine, and [3H]3-quinuclidinylbenzilate ([3H]QNB) binding to calf brain
      membranes. Within a series of phenyltropane carboxylic acid methyl esters the
      most potent analogues were the 4-I and 4-F-phenyl analogs, while replacement of F
      by Cl or alkyl groups diminished potency. The isopropyl and phenylcarboxylic acid
      esters were comparable in potency to the methyl esters. There appeared to be a
      relationship between the potency of the analogs in inhibiting the dopamine
      transporter and nicotine antagonism. A good correlation was observed between
      pharmacologic potency and [3H]mecamylamine binding to brain membranes. It was
      concluded that the antagonistic action of the cocaine analogs involved an ion
      channel site on the neuronal nicotinic cholinergic receptors.

PMID- 7823768
TI  - Increased hematopoietic toxicity following administration of interferon-a with
      combination dideoxynucleoside therapy (zidovudine plus ddI) administered in
      normal mice.
AB  - Because of the urgency to develop drugs which will effectively combat HIV
      infection, many combination therapies which have proved effective against HIV in
      vitro have undergone, or are undergoing clinical trial. Unfortunately many of
      drugs are being used without rigorous and exhaustive preclinical evaluation to
      assess their potential to develop hematopoietic toxicity. We report here the
      results of two in vivo studies performed to analyze the effect of combined
      zidovudine (AZT) plus didanosine (ddI) therapy, either with or without interferon
      a (IFN-a), on murine hematopoiesis. Normal C57BL/6 female mice were administered
      AZT (1.0 mg/ml) plus dose-escalation ddI (0.1, 1.0 and 2.5 mg/ml) placed in their
      drinking water. Control mice received IFN-a (100 units/ml) alone. Mice were
      serially bled and sacrificed over a six-week period for assessment of
      hematopoietic toxicity measured by peripheral blood indices and assays of
      hematopoietic progenitors, i.e., erythroid (BFU-E), myeloid (CFU-GM), and
      megakaryocyte (CFU-Meg) cultured from bone marrow and spleen. AZT plus dose
      escalation ddI decreased the hematocrit and white blood cell count when
      administered to normal mice compared to untreated controls during the six-week
      examination period. Marrow derived BFU-E, CFU-GM, and CFU-Meg were all reduced,
      however an increase was observed from the spleen for all three progenitor cell
      types. Use of IFN-a, in addition to combination AZT plus ddI further decreased
      the hematocrit, white blood cells and platelets. Marrow derived CFU-GM and CFU
      Meg were increased slightly and only marginally for BFU-E with a similar response
      observed from the spleen. These results demonstrate that combination AZT plus ddI
      when used in vivo may produce synergistic hematopoietic toxicity, and that the
      addition of IFN-a to this treatment regimen increases this toxicity. These data
      indicate caution when this therapeutic approach is suggested for patients
      infected with HIV. If used, these patients will require careful monitoring for
      blood cell toxicity.

PMID- 7823769
TI  - Glomerular endothelial cells promote mesangial cell growth via a PDGF-Like
      substance.
AB  - We conducted these experiments to determine whether glomerular endothelial cells
      (GEN) may play a role in the regulation of glomerular mesangial cells (GMC)
      growth. When GMC were separately co-cultured with GEN for 24 h, [3H]thymidine
      incorporation into GMC increased by 22%. In addition, when GMC were co-cultured
      with GEN for 4 days, the GMC count increased statistically. Conditioned medium
      (CM) was obtained from confluent GEN monolayers and tested for its effect on GMC
      growth. When CM was mixed with RPMI 1640 medium containing fetal calf serum
      (final concentration: 10%), GMC growth was potentiated in a dose-dependent
      manner. This stimulatory effect of CM from GEN cultures was inhibited by the
      addition of anti-human platelet-derived growth factor (PDGF) antibody. However,
      antibodies against interleukin 1-beta, tumor necrosis factor-alpha and endothelin
      1 did not affect the stimulatory effect of CM. Moreover, the modulator contained
      in CM was stable at 100 degrees C, and pH 2.5 at 22 degrees C for 30 min. When
      treated with 2 mM mercaptoethanol, this activity was almost completely lost.
      These findings suggest that GEN promote GMC growth in co-culture systems, without
      direct contact, by means of a PDGF-like substance.

PMID- 7823770
TI  - Differential effects of bromopride and domperidone on cholinesterase activity in
      rat tissues.
AB  - Bromopride (BRO) and domperidone (DOMP) are dopamine D2 blocking agents used in
      gastroenterology clinics because of their anti emetic effect as well as their
      central and peripheral actions of increasing gastrointestinal motor activity. The
      rationale for these experiments was to compare BRO- and DOMP-effects on plasma,
      brain, and intestinal cholinesterase activity in vitro. BRO and DOMP effects on
      cholinesterase activity in plasma, striatum, duodenum and ileum of adult male
      rats were measured for drug concentrations ranging from 0.006 to 3.134 microM for
      BRO and from 0.006 to 125 microM for DOMP. The results demonstrate that both BRO
      and DOMP can inhibit cholinesterase activity in all tissues studied, with DOMP
      being more potent than BRO in plasma and intestinal tissues. These data suggest
      the existence of a cholinergic mechanism of action for these dopamine blocking
      agents.

PMID- 7823771
TI  - Inhibition by gangliosides GM3, GD3 and GT1b of substrate phosphorylation by
      protein kinase C in bovine mammary gland and its reversal by phosphatidylserine.
AB  - Effects of gangliosides GM3, GD3 and GT1b on protein kinase C (PKC) activity and
      endogenous protein phosphorylation by PKC were examined in bovine mammary gland.
      The gangliosides inhibited PKC activity in both cytosolic and total particulate
      fractions with IC50 values (concentrations causing 50% inhibition) of 100-115
      microM (GM3), 75-80 microM (GD3) and 20-28 microM (GT1b). Several proteins were
      shown to be substrates for PKC by phosphorylation in the absence or presence of
      the PKC cofactors 1-oleoyl-2-acetyl-sn-glycerol (OAG, 5 micrograms/ml),
      phosphatidylserine (PS, 25 micrograms/ml) and Ca2+ (1 microM). GM3 at 100 microM
      suppressed phosphorylation in cytosol of 91 kDa and 89 kDa proteins. Similar
      suppression of phosphorylation of these proteins was achieved by the addition of
      50 microM GD3 and 10 microM GT1b; thus the order of suppressive capacity for
      substrate phosphorylation was parallel to their IC50 values. GT1b (100 microM)
      inhibited phosphorylation of 56 kDa, 43 kDa and 36 kDa proteins, in addition to
      that of the 91 kDa and 89 kDa ones. Phosphorylation of 72 kDa and 21 kDa proteins
      was resistant even at this concentration, suggesting the selective suppression by
      gangliosides of phosphorylation of individual substrates. In the particulate
      fraction, phosphorylation of a 91 kDa protein was suppressed by 100 microM GT1b,
      whereas phosphorylation of the other substrates was unaffected by any ganglioside
      used. Suppression of phosphorylation of cytosolic 91 kDa and 89 kDa and
      particulate 91 kDa proteins could be reversed by addition of PS (250
      micrograms/ml), but not by OAG (50 micrograms/ml) or Ca2+ (250 microM). These
      results suggest that gangliosides are involved in the regulation of PKC-dependent
      phosphorylation by modulating the association of PKC or its substrates with
      membrane phospholipids.

PMID- 7823772
TI  - Adrenal function response to chronic stress in rats with anterodorsal thalami
      nuclei lesions.
AB  - The effects of chronic stress (forced immobilization, 15 min/day during 12 days),
      on the plasma corticosterone and the adrenal catecholamines response in rats with
      anterodorsal thalami nuclei (ADTN) lesions were studied. In sham lesioned rats,
      chronic stress produced a significant increase in plasma corticosterone (C), as
      compared to unstressed animals (p < 0.05). The adrenal C was, however, similar in
      both groups. There were no differences in plasma C values between unstressed and
      stressed lesioned rats. The adrenal C content, was significantly lower (P <
      0.005) in stressed lesioned rats when compared with unstressed lesioned animals.
      Adrenal norepinephrine (NE) values, in sham lesioned rats after forced
      immobilization, were significantly below those found in unstressed sham lesioned
      ones (P < 0.05). There were no changes in adrenal epinephrine (E) response after
      forced immobilization. In lesioned rats, NE response to chronic stress showed the
      opposite pattern to that in sham lesioned ones; the adrenal glands of these
      animals showed a significant increase in NE content as compared to unstressed
      lesioned rats (P < 0.01). Similar alterations in the adrenal E concentration were
      found, post stress values were significantly higher (P < 0.01).

PMID- 7823773
TI  - Nicotine stimulates pepsinogen secretion from guinea pig gastric chief cells in
      monolayer culture.
AB  - We evaluated the effects of nicotine on pepsinogen secretion in vitro, using a
      monolayer culture system of guinea pig gastric chief cells. Pepsinogen secretion
      was increased by above 5 mM nicotine in a dose-dependent manner, as was the
      elevation of intracellular free calcium concentration ([Ca2+]i). The pepsinogen
      secretion stimulated by 10 mM nicotine was inhibited by above 1 mM d
      tubocurarine, a nicotinic receptor antagonist, but not by same concentrations of
      scopolamine hydrobromide monohydrate or pirenzepine, a muscarinic receptor
      antagonist. The elevation of [Ca2+]i induced by 5 mM nicotine was also reduced by
      10 mM d-tubocurarine, but not by 10 mM pirenzepine. A calmodulin inhibitor, N-(6
      aminohexyl)-5-chloro-1-naphthalene-sulfonamide (W-7), at the concentration of 10(
      6) M and a myosin light-chain kinase inhibitor, 1-(5-chloronaphthalene-1
      sulfonyl)-1H-hexahydro-1,4-diazepine (ML-9), at concentrations above 10(-7) M
      also significantly blocked 10 mM nicotine-induced pepsinogen secretion. These
      finding indicate that nicotine directly stimulates pepsinogen secretion probably
      via nicotinic receptors on the gastric chief cells, and that the Ca(2+)-mediated
      messenger system, including calmodulin and myosin light-chain kinase, is involved
      in this event.

PMID- 7823774
TI  - Kinetic properties of hexose-monophosphate dehydrogenases. I. Isolation and
      partial purification of glucose-6-phosphate dehydrogenase from rat liver and
      kidney cortex.
AB  - Glucose-6-phosphate dehydrogenase (G6PDH) from rat-liver and kidney-cortex
      cytosol has been partially purified and almost completely separated from 6
      phosphogluconate dehydrogenase activity. The purification and isolation
      procedures included high-speed centrifugation, 40-55% ammonium sulphate
      fractionation, by which both enzyme activities were separated, and finally, the
      application of the protein fraction to a column of Sephadex G-25 equilibrated
      with 10 mM Tris-EDTA-NADP buffer, pH 7.6, to eliminate any contaminating
      metabolites. The kinetic properties of isolated liver and renal G6PDH were
      examined. Both enzymes showed a typical Michaelis-Menten kinetic saturation curve
      with no evidence of co-operativity. The optimum pH of both liver and kidney
      cortex G6PDH was 9.4. The Km values for glucose-6-phosphate (G6P) and for NADP
      were 3.29 x 10(-4) M and 1.00 x 10(-4) M respectively. The specific activity
      measured at 37 degrees C and optimum pH was 327.1 mU/ mg of protein. NADPH caused
      a competitive inhibition with a Ki of 10 microM. The Km values for the G6P and
      NADP of kidney-cortex G6PDH were 2.06 x 10(-4) and 0.25 x 10(-4) M respectively.
      The specific activity at pH 9.4 and 37 degrees C was 76.55 mU/mg of protein. The
      Ki value for NADPH inhibition was 4 microM. This work describes an easy, rapid
      and reliable method for the separation of the two dehydrogenases involved in the
      hexose-monophosphate shunt in animal tissues.

PMID- 7823775
TI  - Diurnal variation of the pituitary-adrenal and AVP responses to stress in rats
      under food restriction.
AB  - In the present study plasma corticosterone (B), ACTH and vasopressin (AVP) were
      determined in 2 groups of Wistar rats, a control group (C) with free access to
      food, and a food restricted group (FR) with access to food only from 0900 to 1100
      h for 14 days. Blood samples were collected by decapitation under unstressed
      (basal) conditions and immediately after 30 minutes of immobilization stress
      applied at AM (0800 h) and at PM (2000 h). The basal plasma B concentrations in C
      group presented diurnal variation with higher values at PM than at AM. The
      restricted feeding regimen resulted in a 12 hour shift of peak B values. Basal
      plasma ACTH rhythm in group C is parallel to diurnal B variation, attaining
      higher levels at PM. Rats under food restriction presented higher basal plasma
      ACTH levels at AM than C group, however there was no AM-PM difference. In both
      groups after stress plasma B concentrations increased in comparison to those in
      the unstressed rats. There was no significant AM-PM difference in the absolute B
      values attained in C or FR groups. The stress-evoked ACTH response was higher at
      AM than at PM in group C. In the FR group the ACTH response was similar in the
      morning and evening, although the ACTH concentrations achieved in the morning was
      lower than in group C. Basal plasma AVP levels were similar at AM and PM in both
      C and FR groups. Immobilization stress evoked no plasma AVP response in neither
      groups. Our results indicate that long term food restriction is able to modify
      the diurnal rhythms of both basal secretion and stress responsiveness of
      pituitary-adrenal axis by an as yet uncharacterized mechanism.

PMID- 7823776
TI  - Epithelial cell proliferation and biodistribution of radiolabeled urogastrone in
      the gastrointestinal mucosa of young and old mice.
AB  - We have evaluated epithelial cell proliferation and biodistribution of
      radiolabeled recombinant human urogastrone/epidermal growth factor (125I
      rhUG/EGF) in the gastrointestinal mucosa of young (2+ months) and old (30+
      months) mice. Animals were injected intraperitoneally with the metaphase arrest
      agent vincristine sulfate and intravenously with 125I rhUG/EGF. Animals were
      killed after two hours. Crypt cell production rate and uptake of radiolabeled
      urogastrone were measured in the same intestinal tissues. The results
      demonstrated that older animals had significantly greater crypt cell production
      rate as compared to young. However, the uptake of 125I rhUG/EGF was not
      significantly different (except in duodenum, where the uptake of 125I rhUG/EGF
      was significantly greater in young compared to old animals) between young and old
      animals. This suggests that increased epithelial cell proliferation in the aging
      animals is not associated with increased uptake of 125I rhUG/EGF. Thus epidermal
      growth factor/urogastrone may not be a primary factor for the intestinal kinetic
      differences which exist between young and old animals.

PMID- 7823778
TI  - Terephthalic acid: a dosimeter for the detection of hydroxyl radicals in vitro.
AB  - Hydroxylation reactions of aromatic compounds have been used to detect hydroxyl
      radicals produced by gamma irradiation and ultrasound. The present study
      investigated the suitability of terephthalic acid (THA) as a hydroxyl radical
      dosimeter for general use in biologically relevant reactions. Hydroxyl radicals
      were generated by: (1) irradiating THA with a 254 nm ultraviolet light; (2)
      irradiating with gamma rays from a cesium source; and (3) generating hydroxyl
      radicals with 1 mM H2O2 and 10 microM Cu+2. In each of the three experiments, a
      fluorescent product was generated which exhibited identical fluorescent
      excitation and emission spectra. THA is non-fluorescent, eliminating the problem
      of a high initial background. Because THA has four identical ring hydrogens, only
      one mono-hydroxylated isomer was formed. The hydrogen peroxide reaction was
      dependent on the presence of a metal and cupric ions were effective in enhancing
      the reaction. With a Cu+2 concentration of 10 microM, the reaction was linear
      between 0-30 mM H2O2. Catalase abolished the reaction at a concentration of 100
      micrograms/ml and the effects could still be observed at 10 ng/ml, consistent
      with the very high rate at which catalase destroys hydrogen peroxide. Tertbutyl-
      hydroperoxide did not generate any fluorescence in this system which makes THA a
      very specific detector of hydroxyl radicals.

PMID- 7823777
TI  - Potentiation of intrathecal DAMGO antinociception, but not gastrointestinal
      transit inhibition, by 5-hydroxytryptamine and norepinephrine uptake blockade.
AB  - Spinally administered mu opioid agonists produce potent antinociception and
      inhibition of gastrointestinal transit. Blockade of 5-hydroxytryptamine (5-HT) or
      norepinephrine (NE) uptake potentiates intrathecal (i.t.) DAMGO antinociception.
      To determine whether 5-HT and NE uptake blockade will also potentiate the
      gastrointestinal inhibition, mice were treated with zimelidine, desipramine or
      saline, followed by i.t. DAMGO and tested for tailflick antinociception or
      inhibition of gastrointestinal transit. DAMGO produced antinociception dose
      dependently (ED50 = 4.6 ng). Zimelidine (10 mg/kg, s.c., 1 hr before DAMGO)
      produced a 6.2-fold leftward shift in the antinociceptive dose-response curve
      (ED50 = 0.73 ng). Desipramine produced a 5.3-fold shift (ED50 = 1.4 ng). DAMGO
      also produced a dose-dependent inhibition of gastrointestinal transit (ED50 = 117
      ng). However, zimelidine or desipramine treatment did not affect DAMGO inhibition
      of gastrointestinal transit (ED50 = 80 ng.).

PMID- 7823779
TI  - Tests of the liver specificity of drug glucuronidation.
AB  - Hellerstein and Landau and their coworkers have developed the glucuronide
      conjugate approach to aid in the analysis of pathways of liver carbohydrate
      metabolism. This approach requires that the liver is essentially the sole site of
      glucuronidation of the given drug. Since UDPglucuronyl transferases are present
      also in other tissues, most notably the kidney and intestines, we need to test
      the liver specificity of this process. We develop isotopic approaches to do this,
      based upon a comparison of the specific activity of the conjugate with that of
      plasma glucose and liver glucose-6P.

PMID- 7823780
TI  - Effect of long-term treatment with EGb 761 on age-dependent structural changes in
      the hippocampi of three inbred mouse strains.
AB  - Female mice of the inbred strains C57BL/6J, BALB/cJ and DBA/2J were used to
      determine the possible existence of a genetically-based differential
      susceptibility to the effects of treatment with an extract of Ginkgo biloba (EGb
      761). Timm's silver-sulphide staining method was used to visualize and determine
      changes in the areas of the hippocampal structures of aged subjects, and more
      specifically on the projection fields of the mossy fibers which appear to
      decrease as a function of ageing. Experiments were begun when the animals were 15
      months old. Treated animals received EGb 761 (50 mg/kg/day, p.o.) for 7 months in
      their drinking water. Inter-strain differences existed for the areas of the whole
      regio inferior, stratum pyramidale, stratum lacunosum moleculare and hilus (CA4)
      and for the projection field of intra- and infrapyramidal mossy fibers (iipMF) in
      the CA3 region of the hippocampus. Chronic treatment with EGb 761 significantly
      increased the projection field of iipMF and significantly reduced the area of the
      stratum radiatum, as compared with control mice. No differential sensitivity to
      EGb 761 existed among the mouse strains tested. Antioxydint properties of EGb 761
      may explain its neuroprotective and neurotrophic actions on the hippocampus, and
      might explain certain improvements in memory and other cognitive functions in
      both humans and experimental animals.

PMID- 7823781
TI  - Fluorinated analogues of L-ornithine are powerful inhibitors of ornithine
      decarboxylase and cell growth of Leishmania infantum promastigotes.
AB  - Fluorinated analogues of L-ornithine have been tested on growth and ornithine
      decarboxylase arising from L.infantum cytosolic extracts. EC50 values estimated
      from dose/response curves were 38 microM, 2.62 microM and 4.64 microM for alpha
      DFMO, delta-MFMO and delta-MFMOme respectively. Also the inhibition produced by
      all three compounds was effectively reverted by exogenous putrescine, pointing
      towards the inhibition of L.infantum ODC. ODC from logarithmic phase cytosolic
      extracts was physicochemically and kinetically characterized, showing a long half
      life (more than 24 h) and a km value for L-ornithine of 98 microM. Finally, the
      inhibitory effect of fluorinated analogues of L-ornithine was analysed on
      L.infantum ODC showing a time-dependent irreversible behavior, with Ki values
      estimated on 125 microM, T1/2 3.5 min for alpha-DFMO; 13.3 microM, T1/2 1.8 min
      for delta-MFMO and 4.3 microM, T1/2 4 min for delta-MFMOme.

PMID- 7823782
TI  - Protection from hypoxemic renal dysfunction by verapamil and manganese in the
      rabbit.
AB  - The ability of calcium channel blockers to prevent and/or to reverse the
      hypoxemia-induced renal dysfunction was studied in anesthetized and mechanically
      ventilated rabbits. Renal blood flow (RBF) and glomerular filtration rate (GFR)
      were determined by para-aminohippuric acid and inulin clearance, respectively.
      Each animal was considered as its own control. In 9 rabbits (group 1), verapamil
      infusion, 1 microgram.kg-1.min-1, did not change basal renal hemodynamics. In a
      second group (n = 9), hypoxemia induced marked significant decreases in GFR, RBF
      and urine flow rate (-22 +/- 5%, -18 +/- 6% and -34 +/- 7% respectively). The
      administration of verapamil partially reversed the hypoxemia-induced renal
      dysfunction. Likewise, hypoxemia did not induce any change in renal function in
      verapamil pretreated rabbits (n = 8). This study shows that verapamil is able to
      prevent and to partially reverse the adverse effects of hypoxemia on renal
      hemodynamics. The intrarenal infusion of manganese chloride, another calcium
      channel blocker, was also effective in blunting the hypoxemia-induced changes in
      the left infused kidney, but not in the contralateral kidney. The overall results
      demonstrate that a significant protection from hypoxemic renal dysfunction can be
      achieved by inhibitors of calcium ion transport.

PMID- 7823783
TI  - Hepatic glutathione determination after ethanol administration in rat: evidence
      of the first-pass metabolism of ethanol.
AB  - As a fraction of ingested ethanol is metabolized by gastric mucosa, different
      amounts of alcohol should reach the liver when the same dose is administered by
      oral or intravenous route. Therefore, we investigated the time-course of hepatic
      reduced glutathione (GSH) concentrations after intra-peritoneal or intra-gastric
      load of the same amount of ethanol in the rat. The test was also performed in
      fasted and Cimetidine-treated rats. The oral ethanol administration was followed
      by a less pronounced decrease and by a quicker recovery of hepatic content of GSH
      than after intraperitoneal route. In the fasted rat, basal hepatic GSH
      significantly decreased; after alcohol administration the decrease of hepatic GSH
      was more severe and prolonged than in the fed rat. Cimetidine was shown to be a
      potent inhibitor of gastric ADH. Pre-treatment with Cimetidine did not change the
      basal levels of hepatic GSH, but after oral ethanol load, the decrease of the
      hepatic GSH content was significantly (p < 0.005) more pronounced than in
      controls. This study demonstrates the beneficial effects of gastric ethanol
      metabolism on the liver. The reduced gastric ethanol metabolism, induced by
      fasting or by Cimetidine resulted in a decreased content and delayed recovery of
      liver GSH content.

PMID- 7823784
TI  - Barium resistant potassium current in mammalian skeletal muscle following
      denervation.
AB  - Inward rectifier potassium channels are thought to be related to resting membrane
      potential and in innervated skeletal muscle they are specially sensitive to the
      blocking action of Ba2+ ions. After denervation other channels are known to
      become resistant to their blockers. We study the effect of Ba2+ upon the inward
      rectifier potassium channels after denervation. Rat extensor digitorum longus
      fibers were equilibrated for 150 minutes in 150 mM KCl; when they were returned
      to 5 mM KCl the resting potential went back to its original level with a half
      time of 35 minutes. This repolarization was blocked by 5 mM BaCl2 in innervated
      muscles and in muscles denervated for 7 days, but failed to do so after 14 days
      of denervation. Voltage-clamp experiments performed in lumbricalis denervated
      muscle showed a lack of effect of Ba2+ upon potassium current after 18 days of
      denervation. This results suggest that the inward rectifier potassium channels
      become resistant to Ba2+ ions after denervation, indicating a neural influence.

PMID- 7823785
TI  - Attenuation of the magnitude of suckling-induced prolactin release with advancing
      lactation: mechanisms.
AB  - To study why suckling-induced plasma prolactin levels decline in magnitude with
      advancing lactation, we examined prolactin release in lactating rats following
      suckling and pharmacologic manipulations during early, mid- and late lactation.
      On day 2 of lactation, litters were adjusted to 8 pups. On day 3, dams were
      implanted with an atrial catheter and experiments were conducted on lactation
      days 5, 11 and 17. To examine suckling-induced prolactin release, pups were
      removed at 0800 h, an extension was attached to the catheter at 1100 h, and pups
      returned to dams at 1200 h. Blood samples were obtained before, and at 10, 30,
      60, 90 and 120 min after suckling started. Prolactin responses to sulpiride and
      thyrotropin releasing hormone (TRH) administration were studied in lactating rats
      separated from their litters for 4 hours. Blood samples were obtained before, and
      at 10, 30, 60 and 90 min after sulpiride (10 or 40 micrograms/kg BW) and 5, 10,
      20 and 30 min after TRH (1 or 4 micrograms/kg BW) in rats pretreated with
      sulpiride. Prolactin release in response to suckling, administration of sulpiride
      or sulpiride and TRH diminished as lactation advanced. From these results, we
      conclude that refractoriness in anterior pituitary lactrotropes to prolactin
      releasing stimuli is at least partially responsible for the decline in suckling
      induced prolactin release with advancing lactation.

PMID- 7823786
TI  - Bile salt secretion by hepatocytes incubated with bile salts and liposomes or low
      density lipoproteins.
AB  - The purpose of this work was to determine the effect of exogenous unesterified
      cholesterol provided in either artificial liposomes or LDL on bile salt synthesis
      by isolated rat hepatocytes. Rates of de novo synthesis were determined in the
      presence of 300 or 600 microM taurocholate, 600 microM taurodehydrocholate,
      cholate, deoxycholate or chenodeoxycholate. There was no significant difference
      between the cholesterol uptake by hepatocytes when the degree of hydrophobicity
      of the bile salts changed (cholate vs deoxycholate or chenodeoxycholate).
      Compared to taurocholate, taurodehydrocholate lowered the hepatic incorporation
      of unesterified cholesterol for the first 60 minutes; compared to control,
      taurocholate stimulated the cholesterol incorporation for the first 20 minutes. A
      possible explanation for this finding would be an interaction between bile salts
      and exogenous cholesterol, depending on the kind of conjugated bile salt.
      Taurocholate increased the exchange of cholesterol between liposomes or LDL and
      hepatocyte membranes. It resulted in a significant increase of bile salt
      synthesis and secretion. This phenomenon was not observed with
      taurodehydrocholate.

PMID- 7823787
TI  - A dopamine D3 receptor agonist, 7-hydroxy-N,N-di-n-propyl-2-aminotetralin,
      reduces gastric acid and pepsin secretion and experimental gastric mucosal injury
      in rats.
AB  - Dopamine D1/DA1 agonists are associated with significant gastroprotective and
      antisecretory effects. The new dopamine DA3 agonist, 7-hydroxy-N,N-di-n-propyl-2
      aminotetralin (7-OHDPAT), possesses neural and behavioral properties that are
      similar to those of DA1 agonists. In the present experiments, the effects of 7
      OHDPAT on gastric acid secretion in conscious and anaesthetized rats, on
      restraint stress-induced gastric mucosal injury and on gastric adherent mucus
      levels were examined. 7-OHDPAT (2.5, 5.0 and 10.0 mg/kg) reduced significantly
      basal gastric acid secretion in conscious rats (66%, 92% and 78% inhibition,
      respectively). 7-OHDPAT also reduced significantly gastric acid and pepsin
      secretion in pylorus-ligated rats. 7-OHDPAT reduced stress-induced gastric
      mucosal injury at doses of 1.0, 5.0 and 10.0 mg/kg. Gastric adherent mucus was
      preserved only at the 5.0 mg/kg dose. Neither pretreatment with the DA1
      antagonist, SCH23390, nor with the DA2 antagonist, eticlopride, affected 7-OHDPAT
      induced reductions in gastric secretion or gastric mucosal injury. Although
      dopamine DA3 receptors exhibit greater amino acid sequence homology with DA2
      receptors than with DA1 receptors, the possibility nevertheless exists that some
      of the gastrointestinal actions of dopamine and its agonists--both anti-secretory
      and gastroprotective--may be exerted through activation of DA3 receptors.

PMID- 7823788
TI  - Domestic violence made real.

PMID- 7823789
TI  - Keeping expert nurses expert.

PMID- 7823790
TI  - Personal liability insurance.

PMID- 7823791
TI  - What size feeding tube?

PMID- 7823792
TI  - Strategies for using interviewing skills in patient teaching.

PMID- 7823793
TI  - One approach to immunizing children.

PMID- 7823794
TI  - Using the Oucher developmental approach to pain assessment in children.

PMID- 7823795
TI  - Preventing abuse during pregnancy: an assessment and intervention protocol.

PMID- 7823796
TI  - A case study: organic acidemia.

PMID- 7823797
TI  - Folic acid will reduce risk of neural tube defects.

PMID- 7823798
TI  - Treating congenital cataracts.

PMID- 7823799
TI  - An alternative to meet the needs of early discharge: the tender beginnings
      postpartum visit.

PMID- 7823800
TI  - Sampling design: Part I.

PMID- 7823801
TI  - Beta2 agonists and maintenance drugs in the treatment of asthma.

PMID- 7823803
TI  - Oswaldo Goncalves Cruz 5.8.1872-11.2.1917.

PMID- 7823802
TI  - [Methods of establishing occupational and environmental hygienic norms].

PMID- 7823804
TI  - A Salmonella agona outbreak in a pediatric hospital in the city of Rio de
      Janeiro, Brazil.
AB  - Six Salmonella Agona strains from an outbreak of 15 days duration which occurred
      in a public hospital in Rio de Janeiro, Brazil, were analyzed. The outbreak
      involved six infants (mean age, 24 days; mean body weight, 1612 g), all of them
      with severe clinical signs and symptoms. Two of them had surgical implications,
      two were preterm and two had respiratory distress at birth. The Salmonella
      strains were resistant to nine antimicrobial agents (ampicillin, cefalotine,
      ceftriaxone, gentamicin, amikacin, trimethoprim-sulfamethoxazole,
      chloramphenicol, and tetracycline). Analysis of the plasmid pattern of the wild
      strains and of the transconjugants confirmed that these were identical strains.

PMID- 7823806
TI  - Trypomastigotes in cultures of Blastocrithidia culicis (Novy, MacNeal & Torrey,
      1907) (Kinetoplastida: Trypanosomatidae).

PMID- 7823805
TI  - Factors influencing predation of the waterbugs Sphaerodema annulatum (Fab). and
      S. rusticum (Fab.) on the disease transmitting snail Lymnaea (Radix) luteola
      (Lamarck).
AB  - Variations in the rate of predation of the waterbugs Sphaerodema annulatum and S.
      rusticum on the snails Lymnaea (Radix) luteola have been noted in respect to the
      morphs of the waterbugs, size of the prey individuals, densities of prey and
      predators, temperature and surface area of the waterbody concerned and the
      seasons. Consumption rate was highest (7.2 and 2.2 individuals per day per
      individual of S. annulatum and S. rusticum, respectively) in prereproductive ages
      of the waterbugs. This was followed by a gradual decline with the increase in age
      of the predators. The consumption rate was gradually higher with the increase of
      temperature from 20 degrees C to 35 degrees C. The bugs failed to survive beyond
      35 days at 35 degrees C. Though the bugs prey upon the snails of all sizes
      preference for 6.5 x 4.5 mm to 8 x 5 mm individuals by S. annulatum and for 5 x 3
      mm to 6.5 x 4.5 mm individuals by S. rusticum is established. The waterbugs,
      irrespective of species, consumed the snail individuals belonged to 3 x 2 - 4 x 3
      mm size group maximum when supplied separately. The rate of predation gradually
      declined with the rise of predator's density irrespective of waterbug species.
      Predation rate increased with increasing prey density. This was level off when
      the prey snails were 1100 and 700 in number for S. annulatum and S. rusticum
      respectively. An adult S. annulatum and S. rusticum consumed 5.04, 3.7, 1.43 and
      3.36, 2.49, 1.04 snails per day respectively in summer, monsoon and winter.

PMID- 7823807
TI  - Correlation between anti-V3 peptide and neutralizing antibodies in plasma from
      HIV-1 infected individuals resident in Brazil.

PMID- 7823808
TI  - Bengal: El Tor cholera vibrio in a new robe.

PMID- 7823809
TI  - The effect of cholera toxin and its toxoid on ileal loops of the rat.

PMID- 7823810
TI  - Echinopardalis sp. (acanthocephala, oligacanthorhynchidae) eggs in felid
      coprolites dated from 9,000 years before present, found in the Brazilian
      northeast.

PMID- 7823811
TI  - Natural infection of Phyllocaulis soleiformis with larvae morphologically similar
      to L2 of Angiostrongylus costaricensis.

PMID- 7823812
TI  - Parasitism by Primasubulura jacchi (Marcel, 1857) Inglis, 1958 and Trichospirura
      leptostoma Smith and Chitwood, 1967 in Callithrix penicillata marmosets, trapped
      in the wild environment and maintained in captivity.

PMID- 7823813
TI  - Long-term patency of blood parasitism by Trypanosoma minasense and Microfilariae
      in Callithrix penicillata marmosets (Primates, Callitrichidae), caught at the
      wild and maintained in captivity.

PMID- 7823814
TI  - Noteworthy records of Ixodes auritulus Neumann, 1904 (acari, ixodida) on birds
      from Parana, southern Brazil.

PMID- 7823815
TI  - Ultrastructural aspects of virus replication in one fatal case and several other
      isolates from a dengue type 2 outbreak in Rio de Janeiro.
AB  - Dengue virus replication in mosquito cell cultures was observed by electron
      microscopy in one fatal and 40 classical isolates from a dengue type 2 outbreak
      in Rio de Janeiro and compared with the prototype New Guinea C strain. All the
      Brazilian isolates presented, beside the classical structured dengue virus
      particles, fuzzy coated virus-like particles, never observed in the referencial
      New Guinea C virus strain. More numerous DEN-2 virus particles, fuzzy coated
      virus-like particles, defective virus particles and smooth membrane structures
      inside the rough endoplasmic reticulum characterized the unique fatal isolate
      examined.

PMID- 7823816
TI  - Notes on the biology of Amblyomma dissimile Koch, 1844 (Acari:Ixodida) on Bufo
      marinus (Linnaeus, 1758) from Brazil.
AB  - Amblyomma dissimile is a common ectoparasite of cold blooded animals and is an
      accidental ectoparasite of some wild mammals. Details of the biology of specimens
      from the State of Amapa were studied in the laboratory in a humidity chamber at
      an average environmental temperature of 19.5 degrees C, using Bufo marinus as
      host for the time in Brazil. We also report the first record of this species in
      the State of Minas Gerais.

PMID- 7823817
TI  - Helminth parasites of conventionally maintained laboratory mice.
AB  - The spectrum of intestinal parasites present in the Swiss Webster, C57B1/6 and
      DBA/2 mice strains from different animal houses was identified and prevalences
      compared. Three parasites were observed during the course of this study, namely
      the cestode Vampirolepis nana (Siebold, 1852) Spasskii, 1954 (= Hymenolepis nana)
      and the nematodes Aspiculuris tetraptera (Nitzsch, 1821) Schultz, 1924 and
      Syphacia obvelata (Rudolphi, 1802) Seurat, 1916. The scope of this investigation
      has been widened to also include morphometric data on the parasites, to further
      simplify their identification, since the presence of helminths in laboratory
      animals is regarded as a restricting factor for the proper attainment of
      experimental protocols.

PMID- 7823818
TI  - Trypanosoma cruzi infection in the opossum Didelphis marsupialis: absence of
      neonatal transmission and protection by maternal antibodies in experimental
      infections.
AB  - The high rate of natural Trypanosoma cruzi infection found in opossums does not
      always correlate with appreciable densities of local triatomid populations. One
      alternative method which might bypass the invertebrate vector is direct
      transmission from mother to offspring. This possibility was investigated in five
      T. cruzi infected females and their litters (24 young). The influence of maternal
      antibodies transferred via lactation, on the course of experimental infection,
      was also examined. Our results show that neonatal transmission is probably not
      responsible for the high rate of natural T. cruzi infection among opossums. In
      addition antibodies of maternal origin confer a partial protection to the young.
      This was demonstrated by the finding of a double prepatency period and 4, 5 fold
      lower levels of circulating parasites, in experimentally infected pouch young
      from infected as compared to control uninfected mothers. On the other hand, the
      duration of patent parasitemia was twice as long as that observed in the control
      group.

PMID- 7823819
TI  - A simple and economic slide micro-immunoenzymatic (micro-SIA) test for
      epidemiological studies of toxoplasmosis.
AB  - A slide micro-immunoenzymatic assay (micro-SIA) to detect antibodies to non
      particulate Toxoplasma gondii antigens is described. This assay allows the
      diagnosis of toxoplasmosis infection in about 1 hr. Twenty-four determinations
      can be performed per slide. Five hundred ng of antigen and 5 or 10 microliters
      drop of each reactive are necessary per well. The clear contrast of colours
      obtained for negative and positive sera after the test is finished, allows direct
      discrimination of the results. However, it is possible to quantify the results of
      the reaction using a minireader. Sera dilution cutoff value, determined as the
      most frequent titre for the general population, is 1:100. The toxoplasma micro
      SIA correlates well with indirect immunofluorescence (IIF), its sensitivity is at
      least three times as much as IIF. The test has an intra and inter assay variation
      coefficient of 5.46% and of 6.24% respectively. Sera obtained at random from
      argentinian people were analyzed and a 56% of infection was found. The main
      features of the Toxoplasma micro-SIA are its simplicity, sensitivity,
      reproducibility, and the virtual absence of background making it very suitable
      for screening tests.

PMID- 7823820
TI  - An outbreak of diarrhoea associated with rotavirus serotype 1 in a day care
      nursery in Rio de Janeiro, Brazil.
AB  - Faeces from 17 children less than 1.6 years old and 15 adults more than 22 years
      old were collected during an outbreak of gastroenteritis in a day care nursery
      and screened for the presence of adenovirus and rotavirus by enzyme immunoassay
      (EIARA) and other viruses by electron microscopy (EM) and polyacrylamide gel
      electrophoresis (PAGE). Ten samples (58.8%) from children and one (6.7%) from
      adults were positive for rotavirus and all samples were negative for bacteria and
      parasites. No other viruses were observed in EM. An enzyme immunoassay test using
      monoclonal antibodies (MAb-EIA) to determine the subgroup(s) and the serotype(s)
      of rotavirus was performed and the results showed that all positive samples
      belong to serotype 1, subgroup II of group A rotaviruses. In PAGE test all
      samples had the same profile and the 10 and 11 dsRNA segments corresponded to the
      "long" profile of group A of rotaviruses. These results corroborated the MAb-EIA
      results and indicate a sole source of infection. The major symptoms observed
      were: vomiting (60%), fever (70%) and diarrhoea (100%). In previous years (1989
      to 1991) we observed only rotavirus serotype 2 in this same day care nursery, but
      no outbreak was reported.

PMID- 7823821
TI  - Standardization and evaluation of ELISA for the serodiagnosis of amoebic liver
      abscess.
AB  - An ELISA test for the serological diagnosis of amoebic liver abscess (ALA) was
      standardized and evaluated in sera from three groups of patients: (1) three
      patients with diagnosis confirmed by isolation of the parasite, (2) thirty seven
      patients with diagnosis established by clinical findings and ultrasound studies
      and (3) seven patients whose diagnosis were established by clinical findings and
      a positive double immunodifusion test. Ninety one serum samples from healthy
      subjects and 22 from patients with other liver or parasitic diseases were also
      included in the study. The optimum concentration of Entamoeba histolytica antigen
      was 1.25 micrograms/ml and optimum dilutions of serum and anti-human IgG 
      alkaline phosphatase conjugate were 1:400 and 1:4000 respectively. The cut-off
      point of the ELISA test in this study was an absorbance value of 0.34. The test
      parameters were: sensitivity = 95.7%, specificity = 100%, positive predictive
      value = 100% and negative predictive value = 98.2%. The ELISA test was found to
      be of great use as a diagnostic tool for the establishment of amoebic etiology in
      patients with clinical supposition of ALA. The test could also be used for
      seroepidemiological surveys of the prevalence of invasive amoebiasis in a given
      population, since it allows the processing of a greater number of samples at a
      lower cost than other serological tests.

PMID- 7823822
TI  - Parasite and egg burden, hepatic collagen and histologic pattern of liver
      granulomas in selection III high and low antibody responder mice infected with
      Schistosoma mansoni.
AB  - Selection III mice have particular immunological characteristics: they are high
      (H III) or low (L III) antibody producer animals, yet both lines display similar
      T cell responses and macrophage activities. We submitted these mice to infection
      with Schistosoma mansoni to assess in vivo parasite and egg burden, hepatic
      collagen and cellular composition of granulomas in both lines. Titration of anti
      Schistosoma IgG by ELISA showed remarkably higher values in H III line, at both
      studied periods (8th and 12th weeks post-infection). Nevertheless, the number of
      adult worms recovered from the portal system was similar in both lines, being not
      associated with anti-Schistosoma antibody levels. There is an increase in hepatic
      collagen from the 8th to the 12th weeks post-infection, which is paralleled by an
      increase in the number of eggs in the liver. This association apparently occurs
      at the same ratio in H III and L III animals. The most important difference found
      between the two lines was the outstanding contrast in terms of volume and
      eosinophil counts in the granulomas, with lesions from H III mice clearly being
      larger and containing more of these cells than LIII lesions.

PMID- 7823823
TI  - Sialoglycoconjugates in Trypanosoma cruzi-host cell interaction: possible
      biological models--a review [corrected].
AB  - A number of glycoconjugates, including glycolipids and glycoproteins, participate
      in the process of host-cell invasion by Trypanosoma cruzi and one of the most
      important carbohydrates involved on this interaction is sialic acid. It is known
      that parasite trans-sialidase participates with sialic acid in a coordinated
      fashion in the initial stages of invasion. Given the importance of these
      sialoglycoconjugates, this review sets out various possible biological models for
      the interaction between the parasite and mammalian cells that possess a
      sialylated receptor/ligand system.

PMID- 7823824
TI  - Induction of synthesis of the rat cystatin S protein by the submandibular gland
      during the acute phase of experimental Chagas disease.
AB  - Rats experimentally infected with Trypanosoma cruzi Y strain exhibited
      hypertrophy of the submandibular gland at 18 days after infection. SDS-PAGE of
      infected rats saliva revealed the presence of an additional band with an apparent
      molecular weight of about 13KDa. Electrophoresis of protein saliva and
      immunochemical analysis with antibody against rat cystatin S confirmed that the
      protein was identical to that induced by beta adrenergic stimulation.

PMID- 7823825
TI  - Survey of the irp2 gene among Yersinia pestis strains isolated during several
      plague outbreaks in northeast Brazil.
AB  - The irp2 gene codes for a 190 kDa protein (HMWP2) synthesized when highly
      pathogenic Yersinia are grown under conditions of iron starvation. In this work,
      the presence of irp2 in strains of Y. pestis isolated from different hosts during
      several plague outbreaks in the foci of Northeast Brazil was studied. For this
      purpose, 53 strains were spotted onto nylon filters and their DNA was hybridized
      with the A13 probe which is a 1 kb fragment of the irp2 coding sequence. All
      strains except two hybridized with the probe. However, when the initial stock
      culture of these two strains were analyzed, they both proved to be positive with
      the A13 probe, indicating that the locus was lost after subculture in vitro but
      was always present in vivo. To examine the degree of conservation of the
      chromosomal fragment carrying irp2 among Brazilian strains, the hybridization
      profiles of 15 strains from different outbreaks, different hosts and different
      foci were compared. The hybridization profiles of these strains were all
      identical when their DNA was digested with either EcoRI, EcoRV or AvaII,
      indicating that the restriction sites surrounding the irp2 locus are very well
      conserved among Northeast Brazilian strains of Y. pestis. Altogether, these
      results suggest that the irp2 chromosomal region should be of prime importance
      for the bacteria during their multiplication in the host.

PMID- 7823827
TI  - Protein recovery, separation and purification. Selection of optimal techniques
      using an expert system.
AB  - The paper discusses the utilization of new techniques to select processes for
      protein recovery, separation and purification. It describes a rational approach
      that uses fundamental databases of protein molecules to simplify the complex
      problem of choosing high resolution separation methods for multi component
      mixtures. It examines the role of modern computer techniques to help solving
      these questions.

PMID- 7823826
TI  - Effect of magnesium chloride and guanidinium chloride on the extraction of
      components of extracellular matrix from chicken cartilage.
AB  - In order to evaluate the effect of chaotropic agents on proteoglycan and non
      collagenous proteins, chicken xiphoid cartilage was treated with guanidine-HCl
      and MgCl2 in different concentrations (1M to 5M), and different periods of time
      (12, 24, 48 and 72 hr). The maximum yield of uronic acid was obtained with 3M
      MgCl2 (73.3%). Concentrations of 4M and 5M of MgCl2 showed that much less uronic
      acid was removed, 55.3% and 38.1% respectively. Extraction with 3M MgCl2 and 3M
      guanidine-HCl resulted better efficiency when performed for 48 hr. Analysis by
      SDS-PAGE of the extracts obtained with guanidine-HCl and MgCl2 in different
      concentrations pointed out that most components are equally removed with the two
      solvents, showing that the extraction with MgCl2 is an alternative assay to
      remove non-collagenous proteins from extracellular matrix.

PMID- 7823828
TI  - Model-independent quantification of measurement error: empirical estimation of
      discrete variance function profiles based on standard curves.

PMID- 7823829
TI  - Impact of variance function estimation in regression and calibration.

PMID- 7823830
TI  - Application of the Kalman filter to computational problems in statistics.

PMID- 7823831
TI  - Modeling chemical reactions: Jacobian paradigm and related issues.

PMID- 7823832
TI  - The mathematics of biological oscillators.

PMID- 7823833
TI  - Diffusion-modulated energy transfer and quenching: analysis by numerical
      integration of diffusion equation in laplace space.

PMID- 7823834
TI  - Parameter estimates from nonlinear models.

PMID- 7823835
TI  - Maximum entropy method of data analysis in time-resolved spectroscopy.

PMID- 7823836
TI  - Analysis of kinetic data: practical applications of computer simulation and
      fitting programs.

PMID- 7823837
TI  - Determination of rate and equilibrium binding constants for macromolecular
      interactions by surface plasmon resonance.

PMID- 7823838
TI  - Analysis of nonequilibrium dynamics of bound, free, and total plasma ligand
      concentrations over time following nonlinear secretory inputs: kinetics of two or
      more hormones pulsed into compartments containing multiple variable-affinity
      binding proteins.
AB  - Equations (1) through (8) provide a general mathematical model of combined
      pulsatile and basal effector molecule secretion, distribution, association,
      dissociation, and metabolic removal. Independent and interactive dynamics of
      multiple effector molecules and multiple distinct acceptor/transport proteins can
      be modeled explicity to test relevant hypotheses of ligand binding and clearance.

PMID- 7823839
TI  - Effects of heteroscedasticity and skewness on prediction in regression: modeling
      growth of the human heart.

PMID- 7823840
TI  - Testing pulse detection algorithms with simulations of episodically pulsatile
      substrate, metabolite, or hormone release.
AB  - Mathematical computer-assisted simulations of episodic hormone, substrate, or
      metabolite release can be accomplished using explicit algebra and high-speed
      microprocessors. Such simulations are useful to describe the behavior of single
      or multiple pulse generators, as well as the expected output of these systems.
      Simulated series are helpful in evaluating the sensitivity, specificity, positive
      accuracy, and negative accuracy of discrete peak detection methods, and in
      deconvolution analysis. Specifically, deconvolution analysis should recover the
      correct half-life, production rate, frequency, amplitude, mass, and duration of
      pulsatile hormone secretion, and it should accurately estimate concurrent basal
      secretion, if present. Finally, multiple pulse generators provide an interesting
      simulation model for testing random burst concordance, evaluating how the
      surgelike release of a hormone can be accomplished, and assessing the
      interactions among several control systems. Lastly, special problems remain in
      simulating neuroendocrine pulsatility, namely, the impact of multiple binding
      proteins (see Table 1, p. 392 in this volume), the effects of strong and/or
      correlated circadian variations in burst frequency or amplitude or basal
      secretion, the development of improved statements of error and experimental
      uncertainty in the data, and the description of various modes of basal secretion.

PMID- 7823841
TI  - Error analysis of macromolecular structures determined with nuclear magnetic
      resonance data.

PMID- 7823842
TI  - Characterization of enzyme-complex formation by analysis of nuclear magnetic
      resonance line shapes.

PMID- 7823843
TI  - Computer simulations of nuclear Overhauser effect spectra of complex
      oligosaccharides.

PMID- 7823844
TI  - Determining confidence intervals for parameters derived from analysis of
      equilibrium analytical ultracentrifugation data.
AB  - In the above discussion, we have introduced the profiling approach of Bates and
      Watts. It is an easy to implement, empirical approach to the determination of
      confidence intervals for parameters in nonlinear models. We have applied the
      approach to the analysis of equilibrium sedimentation data and have demonstrated
      that, although models for analyzing such data are formally nonlinear they are
      functionally linear. As such, linear approximation confidence intervals for the
      parameters are adequate for these models and data sets. Further, we have been
      able to examine the effect of implementing a multiple independent variable
      approach (in this case, using multiple rotor speeds) on the precision of the
      analysis. We found that the standard errors of the parameters were reduced and
      that this is accounted for by either the increase in the number of data points or
      the decreases in parameter correlation. In this case, profiling helped to
      visualize the effect on the sum of squares surface of reducing parameter
      correlation, making the effect of the small decreases in the correlation of some
      parameters more evident. Using profiling, it should be easy to explore other
      methods for the improvement of the analysis of ultracentrifugation data and to be
      able to quantitate the improvement. With the above discussion as an example, it
      is likely that the profiling approach should be quite useful and broadly
      applicable in the analysis of data in terms of nonlinear models.

PMID- 7823845
TI  - Boundary analysis in sedimentation velocity experiments.

PMID- 7823846
TI  - Statistical thermodynamic analysis of differential scanning calorimetry data:
      structural deconvolution of heat capacity function of proteins.

PMID- 7823847
TI  - Artifacts of Fourier series analysis.

PMID- 7823848
TI  - Analysis of two-dimensional differential scanning calorimetry data: elucidation
      of complex biomolecular energetics.

PMID- 7823849
TI  - Monte Carlo simulations of membranes: phase transition of small unilamellar
      dipalmitoylphosphatidylcholine vesicles.

PMID- 7823850
TI  - Analysis of drug-DNA binding isotherms: a Monte Carlo approach.
AB  - Monte Carlo simulations of neighbor exclusion models have been used to
      demonstrate the importance of collecting and fitting data over a wide range of
      saturation. Low saturation data are important for good estimates of the affinity
      K of a drug or protein for the lattice site. High saturation data are important
      for distinguishing between negatively cooperative and noncooperative binding
      modes. Neglect of negative cooperativity (omega < 1) has in general little effect
      on the estimation of K. The error is mostly absorbed by increasing the value of
      n. This kind of behavior was previously observed with the fitting of nonideal,
      monomer-dimer, ultracentrifugation data where variations in B, the second virial
      coefficient, and K2, the dimerization equilibrium constant, are highly
      correlated, thus making their individual determination difficult. Within
      experimental error the distinction between a noncooperative model [Eq. (1)] and a
      negatively cooperative model [Eq. (3) or (4) with omega < 1] may require
      additional evidence to justify the choice of one model over another. For example,
      for homogeneous lattices of synthetic deoxyoligonucleotides, n may be constrained
      with some validity, thus allowing a more accurate and precise determination of K
      and omega. In fact, n may be established independently, for example, by nuclear
      magnetic resonance (NMR) methods. However, the assumption of an integral value of
      n for natural DNA samples may not be valid because of sequence heterogeneity.
      Unconstrained fitting of negatively cooperative data to Eq. (4) will thus be a
      very difficult problem (Table V). At an experimental error of only 2.3%, n and K
      can be reasonably determined but with a large error in omega. Data from the final
      20% of saturation are essential in extracting omega. This may in part explain the
      absence of more reports of negatively cooperative behavior in the literature.
      This analysis is independent of the systematic error that may be induced by the
      transformation of data to the Scatchard plot, or the omission of drug self
      association, or the occurrence of wall binding by ligand, or variable point
      density, or non-Gaussian noise, or the occurrence of another mode of binding
      distinct from the models of McGhee and von Hippel. Each of these will introduce
      additional error, possibly biased error, in the parameters estimated; however,
      this does not obviate our conclusion. Even under these ideal circumstances there
      are serious limitations that must be considered when fitting neighbor exclusion
      model data. The direct fitting of absorbance data [to Eq. (2) or functions that
      incorporate other parameters] will also be sensitive to these considerations.

PMID- 7823851
TI  - Analysis of multidimensional spectroscopic data to monitor unfolding of proteins.

PMID- 7823852
TI  - Estimating binding constants for site-specific interactions between monovalent
      ions and proteins.

PMID- 7823853
TI  - Pattern recognition metric for comparison of protein structures based on amino
      acid sequences.

PMID- 7823854
TI  - Quantification of evolution from order to randomness in practical time series
      analysis.
AB  - The principal focus of this chapter is the description of a recently developed,
      readily usable regularity statistic, ApEn, that quantifies the continuum from
      perfectly orderly to completely random in time series data. Several properties of
      ApEn facilitate its utility for practical time series analysis: (1) ApEn is
      nearly unaffected by noise of magnitude below a de facto specified filter level;
      (2) ApEn is robust to outliers; (3) ApEn can be applied to time series of 100 or
      more points, with good confidence (established by standard deviation
      calculations); (4) ApEn is finite for stochastic, noisy deterministic, and
      composite (mixed) processes, the last of which are likely models for complicated
      biological systems; (5) increasing ApEn corresponds to intuitively increasing
      process complexity in the settings of (4). This applicability to medium-sized
      data sets and general stochastic processes is in marked contrast to capabilities
      of "chaos" algorithms such as the correlation dimension, which are properly
      applied to low-dimensional iterated deterministic dynamical systems. The
      potential uses of ApEn to provide new insights in biological settings are thus
      myriad, from a perspective complementary to that given by classic statistical
      methods. The ApEn statistic is typically calculated by a computer program, with a
      FORTRAN listing for a "basic" code referenced above. It is imperative to view
      ApEn as a family of statistics, each of which is a relative measure of process
      regularity. For proper implementation, the two input parameters m (window length)
      and r (tolerance width, de facto filter) must remain fixed in all calculations,
      as must N, the data length, to ensure meaningful comparisons. Guidelines for m
      and r selection are indicated above. We have found normalized regularity to be
      especially useful; "r" is chosen as a fixed percentage (often 15 or 20%) of the
      SD of the subject rather than of a group SD. This version of ApEn has the
      property that it is decorrelated from process SD, in that it remains unchanged
      under uniform process magnification or reduction; thus we can entirely separate
      the questions of SD change and regularity change in data analysis. Because
      regularity questions are thematically orthogonal to the type of information that,
      for example, moment statistics ascertain, we highly recommend that ApEn be used
      in conjunction with other such statistics, rather than as a sole indicator of
      process typicality. Last and yet foremost, we recommend the following order of
      detail in Practical analysis. First, either visually or algorithmically,
      eliminate outliers.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7823855
TI  - Fluorescence lifetime imaging microscopy: homodyne technique using high-speed
      gated image intensifier.
AB  - In the previous sections we demonstrated imaging of intracellular Ca2+ using our
      approach to FLIM. What other analytes can be imaged using FLIM? We have now
      characterized the lifetime of a good number of ion indicators. Based on these
      studies we know that Cl- can be imaged using FLIM with probes such as SPQ or
      MQAE, pH can be imaged using resorufin and probes of the SNAFL and SNARF
      (Molecular Probes) series, and Mg2+ can be imaged using Magnesium Green, Mag-quin
      2, or Mag-quin-1 (Molecular Probes). At present, the probe for K+, as PBFI, are
      just adequate as a lifetime probe, but it seems likely that newer probes for Na+
      (Sodium Green) and K+ will be practical for effective imaging. Of course, imaging
      of oxygen is possible using a wide variety of fluorophores. It should be noted
      that a wide variety of substances and/or phenomena are known to alter decay
      times, acting as quenchers. These include the phenomena of resonance energy
      transfer, collisional quenching, temperature effects, and viscosity effects.
      Also, the FLIM method is not limited to microscopic objects but can be possibly
      used in remote imaging of any object. Hence, FLIM will allow the imaging of the
      chemical and physical properties of objects based on the effects of the local
      environment on the decay kinetics of fluorophores. The instrumentation for FLIM
      is presently complex and requires a moderately complex laser source, a gain
      modulated image intensifier, and a slow-scan CCD camera. However, one can readily
      imagine the instrumentation becoming rather compact, and even all solid-state,
      owing to advances in laser and CCD technologies and, more importantly, advances
      in probe chemistry. To be specific, the dye laser shown in Fig. 1 may be replaced
      by a simpler UV laser, such as the 354 nm HeCd laser which has become available
      (Fig. 11). Intensity modulation of a continuous wave sources can be accomplished
      with acoustooptic modulators. The scientific slow-scan CCD cameras are presently
      rather expensive, but they are used in the present instrumentation because of
      their linearity and high dynamic range. However, the increasing use of CCD
      detectors suggest that even the scientific-grade CCD cameras will soon become
      less costly. Additionally, the frame rates of these detectors continue to
      increase in response to the need for faster imaging. Furthermore, the performance
      of the video CCD cameras is increasing, as seen by the introduction of 10-bit
      video analog-to-digital (A/D) converters.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7823856
TI  - Computations of time-dependent photon migration for biomedical optical imaging.
AB  - In summary, Table II is a listing of the pitfalls and advantages of using Monte
      Carlo simulations and numerical solution of the diffusion equation to describe
      photon migration in tissues. Judicious use of these techniques to describe the
      solution to the forward imaging problem may allow determination of the best
      theoretical resolution and the smallest detectable volume for the range of
      optical property differences expected in situ or imposed by contrast agent
      administration. Furthermore, an understanding of the forward imaging problem
      through these numerical techniques also contributes to our understanding of the
      most efficient solution to the inverse imaging problem.

PMID- 7823857
TI  - Applying bifurcation theory to enzyme kinetics.

PMID- 7823858
TI  - Sequential versus simultaneous analysis of data: differences in reliability of
      derived quantitative conclusions.

PMID- 7823859
TI  - SV40 virus expression vectors.
AB  - SV40 late-replacement vectors provide an excellent means for expressing large
      amounts of proteins from cDNAs of less than 2400 bp. The amount of protein made
      28 hr after infection is sufficient for extremely brief pulse-chase protocols. At
      periods postinfection when cells are still healthy, sufficient protein has been
      made for techniques in which only a small fraction of the protein is detected,
      including immunocytochemistry on cryosections. Because of the ease of subcloning
      DNA fragments into them, the ease of making virus stocks, and the ability to
      achieve comparable amounts of protein expression reproducibly with different
      infections, these vectors are superb tools for comparing series of mutants made
      by site-directed mutagenesis, especially if a normal cellular environment is
      important for the measurements to be made.

PMID- 7823860
TI  - Use of recombinant vaccinia virus vectors for cell biology.

PMID- 7823861
TI  - Use of recombinant adenovirus for metabolic engineering of mammalian cells.

PMID- 7823862
TI  - Amplicon-based herpes simplex virus vectors.

PMID- 7823863
TI  - Replication-defective recombinant herpes simplex virus vectors.

PMID- 7823865
TI  - Inducible protein expression using a glucocorticoid-sensitive vector.

PMID- 7823866
TI  - Expression of exogenous proteins in cells with regulated secretory pathways.

PMID- 7823864
TI  - Cytomegalovirus plasmid vectors for permanent lines of polarized epithelial
      cells.
AB  - Several versions of plasmid vectors that incorporate CMV immediate early
      promoters are now in use. Of particular utility and convenience for making
      permanently transfected polarized cell lines are those that also direct
      expression of a selectable marker. Several methods of transfecting cells are
      available, but the polybrene method is recommended for MDCK cells because it is
      effective, easy, and inexpensive. After transfection, cells are replated in a
      selective drug for 10-14 days to kill untransfected cells; then surviving
      colonies are cloned with cloning rings. Screening of these colonies for
      expression of the desired protein ordinarily yields 10-15% cell lines with
      sufficiently high expression to be useful. It should not be assumed that every
      clone of a polarized cell line will be properly polarized, particularly in the
      case of MDCK cells. However, assays for correct sorting of endogenous markers can
      be used to verify proper polarity of transfectants or to identify well-polarized
      untransfected clones to be transfected. Using these methods and CMV vectors, one
      can easily establish one or more permanently transfected polarized cell lines
      within about 1 mo.

PMID- 7823867
TI  - Expression of foreign proteins in a human neuronal system.
AB  - The NT2N cell system offers an attractive way to overcome some of the technical
      limitations inherent in working with primary neuronal cultures. In particular, it
      is possible to obtain large quantities of neurons with which to perform
      biochemical experiments, and the growth of neurites can be synchronized and
      controlled by varying the substrate on which the cells grow. In addition, because
      the differentiated NT2N neurons are derived from a mitotically active precursor
      cell line in vitro, it is possible to employ a variety of techniques, that are
      not otherwise available when working directly with postmitotic neurons, to obtain
      expression of foreign proteins. Because they are fully polarized, NT2N cells
      offer a way to study protein sorting to axons and dendrites at both the
      biochemical and the morphological level. Further characterization of NT2N cells
      is underway, and more efficient ways to obtain expression of foreign proteins
      will no doubt be found.

PMID- 7823868
TI  - Viruses as model systems in cell biology.

PMID- 7823869
TI  - Homologous recombination for gene replacement in mouse cell lines.

PMID- 7823870
TI  - Regulation of protein activities by fusion to steroid binding domains.

PMID- 7823871
TI  - Gene gun transfection of animal cells and genetic immunization.
AB  - Gene gun technology at this point has the most utility in animal protein
      expression as a back-up technology. In other words, when other conventional
      systems fail, it will generally work. Most notable is its usefulness for hard-to
      transfect cells or in some particular in situ applications. Improvements in the
      gun itself and in the microprojectiles present the potential for this technology
      to expand in utility. The one area in which it now appears to be the method of
      choice is genetic immunization.

PMID- 7823872
TI  - Generation of high-titer pseudotyped retroviral vectors with very broad host
      range.
AB  - Encapsidation of the VSV G protein into the virions of MoMLV-derived retroviral
      vectors in the absence of other VSV-encoded proteins is shown to be an efficient
      process, although the exact mechanism for this process is currently unclear.
      Unlike the conventional retroviral vectors bearing the amphotropic envelope
      protein, the pseudotyped virus has the ability to withstand the shearing forces
      encountered during ultracentrifugation. This property of the pseudotyped virus
      enables the generation of high-titer retroviral vector stocks and has potential
      application for in vivo gene therapy studies. We have found as many as four
      copies of a pseudotyped vector to integrate into the genome of a single cell when
      a high multiplicity of infection was used to infect the cells. Multiple
      integration events were not observed with amphotropic retroviral vectors,
      probably because of their low virus titers. In addition, when retroviral vectors
      are pseudotyped with the VSV G protein, they acquire the host range of VSV and
      are able to infect nonmammalian cells derived from fish, Xenopus, mosquito, and
      Lepidoptera. Since techniques for efficient gene transfer in some of these
      nonmammalian systems are not currently available, retrovirus-mediated gene
      transfer described here should be useful for transgenic and other genetic studies
      in lower vertebrate species. The inability to establish a stable cell line
      expressing the VSV G protein, however, limits large-scale production of the
      pseudotyped retroviral vectors. Generation of stable packaging cell lines for the
      pseudotyped retroviral vectors is a major challenge for the future.

PMID- 7823873
TI  - [G-proteins].

PMID- 7823876
TI  - [Stress. Origin and effects].

PMID- 7823874
TI  - [Protein kinase C. Key enzyme for immune reactions and cell growth].

PMID- 7823875
TI  - [Neural networks].

PMID- 7823877
TI  - Choice of contraceptives.

PMID- 7823878
TI  - The integration sensation.

PMID- 7823879
TI  - The group A beta hemolytic streptococcus. No longer just a nuisance?

PMID- 7823880
TI  - Youth addiction to tobacco.

PMID- 7823882
TI  - Dental clinic fined for refusing to treat AIDS patient.

PMID- 7823881
TI  - Physician frustration leads to MMA reform bill.

PMID- 7823883
TI  - Reducing liability risk in managed care.

PMID- 7823884
TI  - Applying market power--the BHCAG is flexing its muscle. Business Health Care
      Action Group.

PMID- 7823885
TI  - The emergence of managed care and its impact on psychiatry.

PMID- 7823886
TI  - Unbundling the function of an inpatient unit.

PMID- 7823887
TI  - Brief inpatient treatment of dual diagnosis patients.

PMID- 7823888
TI  - Two hundred years of inpatient psychiatry.

PMID- 7823889
TI  - Medical problems in hospitalized psychiatric patients.

PMID- 7823890
TI  - Managing difficult populations.
AB  - Most clinicians will agree that the management of the disruptive patient (and
      other difficult populations) poses frequent and common complications. This
      chapter presents key strategies and philosophies that aid the clinician in
      effectively treating these populations.

PMID- 7823891
TI  - The assessment of outcome and value of psychiatric hospital treatment.

PMID- 7823892
TI  - One axiom and eight corollaries for managing legal issues in an inpatient
      psychiatric setting.

PMID- 7823894
TI  - Lead poisoning among sandblasting workers--Galveston, Texas, March 1994.
AB  - In the United States, an estimated 95% of elevated blood lead levels (BLLs) in
      adults are attributable to occupational exposure (1). This report summarizes the
      findings of an investigation by the Galveston County (Texas) Health District
      (GCHD) of occupational lead poisoning associated with sandblasting during
      February-March 1994.

PMID- 7823893
TI  - Jimson weed poisoning--Texas, New York, and California, 1994.
AB  - Ingestion of Jimson weed (Datura stramonium), which contains the anticholinergics
      atropine and scopolamine, can cause serious illness or death. Sporadic incidents
      of intentional misuse have been reported throughout the United States, and
      clusters of poisonings have occurred among adolescents unaware of its potential
      adverse effects. This report describes incidents of Jimson weed poisoning that
      occurred in Texas, New York, and California during June-November 1994.

PMID- 7823895
TI  - Ectopic pregnancy--United States, 1990-1992.
AB  - Ectopic pregnancy is the leading cause of pregnancy-related death during the
      first trimester (1). Women who have one ectopic pregnancy are at increased risk
      for another such pregnancy and for future infertility (2). In the United States,
      the reported number of hospitalizations for ectopic pregnancy increased from
      17,800 in 1970 to 88,400 in 1989 (1). This report summarizes trends in
      hospitalizations for ectopic pregnancy in the United States during 1990-1992 and
      presents the incidence of ectopic pregnancy in 1992, based on aggregated
      inpatient and outpatient data.

PMID- 7823896
TI  - [A ornithine decarboxylase activity and proliferating cell nuclear antigen in
      gastric cancer].
AB  - To investigate ornithine decarboxylase (ODC) activity and proliferating cell
      nuclear antigen (PCNA) in gastric cancer, ODC activity and PCNA were measured in
      50 resected samples. The relationship between both and clinicopathologic factors
      was examined. ODC activity was 473.3 +/- 54.7 pmol CO2/60 min/mg protein in
      tumors, and 273.5 +/- 38.3 pmol CO2/60 min/mg protein in normal mucosa. ODC
      activity in tumors was significantly higher than that of normal mucosa. ODC
      activity in tumors was significantly high in gross type 4, maximum diameter more
      than 10 cm, depth se, infiltrative growth (INF) gamma, positive lymph vessel
      invasion and positive lymph node metastasis. PCNA-LI was 24.7 +/- 1.5% in tumors,
      and 13.9 +/- 1.1% in normal mucosa. PCNA-LI of tumors was significantly higher
      than that of normal mucosa. PCNA-LI of tumors was significantly high in gross
      type 2, histological type tub 2 and por, depth ss beta and se, IFN beta, positive
      lymph vessel invasion, positive venous invasion, and positive lymph node
      metastasis. ODC activity and PCNA-LI were closely related in normal mucosa,
      showing a correlation coefficient of 0.730. On the other hand, their relationship
      was weak in tumors, showing a correlation coefficient of 0.417. These results
      suggest the differentiation of value between ODC activity and PCNA-LI in gastric
      cancer. In gastric cancer, ODC activity and PCNA-LI in tumors may be good markers
      of lymph node metastasis. Furthermore, PCNA-LI may be a good marker of
      hematogenous metastasis.

PMID- 7823897
TI  - [Expression and prognostic indicators of type 1 and type 2 Lewis blood group
      antigens in colorectal cancers].
AB  - The immunohistochemical analysis using the monoclonal antibodies to the blood
      group antigens was performed on the tissues of 387 colorectal cancers and 307
      normal colonic tissues, and the relation between expression of these antigens and
      prognosis of the patients with stage 2 was also investigated. La, Le(b), and CA
      19-9 were used for type 1 antigens, and Le(x), Le(y), and Sialyl Le(x) for type
      2, respectively. Expression of Ca 19-9 and Silyl Le(x) remarkably increased in
      cancers throughout the colorectum. Le(b) and Le(y) were expressed in only 0-17%
      of the normal distal colon, but in almost colonic tumors. Therefore CA 19-9 and
      Sialyl Le(x) are tumor-associated antigens in the whole colorectum, and Leb and
      Le(y) in the distal colon. Expression of CA 19-9 in primary tumor provided more
      prognostic information and risk of liver metastasis than other Lewis blood group
      antigens.

PMID- 7823898
TI  - [Morphological atypism and clinicopathological factors in colorectal adenoma and
      cancer using nuclear DNA content, p53 and PCNA].
AB  - Cytofluorometric analysis of DNA content and immunohistochemical examination of
      p53 and PCNA were performed in colorectal adenomas, mainly borderline lesions,
      and cancers. Nuclear DNA content revealed aneuploidy and polyploid cells in
      severely atypical adenomas and cancers. Mutated p53 protein was also observed in
      severely atypical adenomas, especially tortuous and villous lesions and cancers.
      PCNA labeling index (P-I) was significantly increased in proportion to cell
      atypism and P-I over 50% was noted in half of severely atypical adenomas. Among
      infiltrating cancers, poorly differentiated adenocarcinoma showed high P-I.
      However, well differentiated adenocarcinoma infiltrating beyond the tunica
      muscularis propria showed various P-I values depending on the presence of
      metastasis to lymph node or blood vessel invasion. Furthermore, P-I in the
      metastatic lesion was significantly higher than that of primary lesion. These
      results suggest that severely atypical adenomas showing morphological features
      such as an increased N/C ratio, loss of polarity, roundish nucleus, tortuous and
      villous change of gland have malignant potentiality. So severely atypical
      adenomas have the clinical indication for polypectomy. In addition, poorly
      differentiated adenocarcinoma shows high proliferative ability and metastatic
      lesions or poorly differentiated components existing in infiltrating cancers may
      affect cancer development as productive clones.

PMID- 7823899
TI  - [An experimental study of arterial graft implantation--the effects of an anti
      thrombin agent, argatroban, and an anti-platelet agent, clopidogrel (SR 25990 C)
      on the inner capsule].
AB  - The anti-thrombogenicity of argatroban and clopidogrel and the influence of these
      two agents on coagulation and fibrinolysis were investigated. After the
      infrarenal abdominal aorta of 21 dogs was replaced with a knitted Dacron
      prosthesis of 5 mm in internal diameter, the inner capsule of the graft was
      evaluated by angioscopy and angiography immediately and 1 week, 2 weeks and 1
      month after surgery. The graft patency rate in group I (untreated group, n = 8),
      group II (argatroban group, postoperative infusion of 1 microgram/kg/min for 2
      weeks, n = 7) and group III (clopidogrel group, postoperative oral administration
      of 12.5 mg/kg/day for 1 month, n = 6) was respectively 75%, 86% and 100% after 1
      week; 75%, 86% and 100% after 2 weeks; and 50%, 71% and 100% after 1 month. The
      mean maximum stenosis measured by angioscopy was 31% in group I, 5% in group II
      and 4% in group III after 1 week; 52%, 23% and 13% after 2 weeks; and 61%, 40%
      and 9% after 1 month. An increase in thrombin antithrombin III complex (TAT) due
      to thrombus was observed in group I, but this was prevented in the treated
      groups. These results suggest that argatroban and clopidogrel are useful anti
      thrombogenic agents for obtaining a thin inner capsule after graft implantation,
      especially in small caliber grafts.

PMID- 7823900
TI  - [A case of umbilical polyp with aberrant pancreas and small intestinal mucosa-
      analysis of cases of umbilical polyp reported in Japan].
AB  - We report a case of a 60 year-old man with an umbilical polyp composed of the
      aberrant pancreas and small intestinal mucosa. This is an extremely rare lesion
      which originates in remnants of omphalomesenteric duct and is usually diagnosed
      in the infant period. Microscopic examination disclosed the aberrant pancreas
      with exocrine glands and ducts, but no islets of Langerhans. The above findings
      suggested that the pancreas might have been HEINRICH II in type.

PMID- 7823901
TI  - [Surgical treatment of needles in intracardiac cavity and chest wall--a case
      report and the review of cases removed under open-heart surgery in Japan].
AB  - A 36-year-old woman under the treatment for neurosis stuck five sewing needles
      into her left anterior chest wall for the purpose of suicide. She was
      hospitalized with complaints of anterior chest pain and low-grade fever. Chest
      roentgenogram and computed tomogram showed two needles in the cardiac cavity and
      three needles in the chest wall. Following extraction of three needles in the
      chest wall, we removed two needles from the left and the right ventricular
      cavities under extracorporeal circulation. Preoperative and intraoperative two
      dimensional echocardiography was useful for confirming the location of needles.

PMID- 7823902
TI  - [A case of bronchogenic cyst at the anterior chest wall].
AB  - Bronchogenic cyst in the subcutaneous region is rare and only 5 cases including
      this case have been reported in Japan. A 2-year-old boy was admitted to our
      hospital because of congenital mass at the anterior chest wall. Ultrasonography
      showed a 29 x 9 mm sized well-defined tumor with homogeneous low echogenicity in
      the subcutaneous tissue. Extirpation of the tumor was performed. Histologically,
      ciliated columnar epithelia with the surrounding smooth muscle and seromucous
      glands were observed. Diagnosis of bronchogenic cyst was made. Postoperative
      course was uneventful and no tumor has recurred.

PMID- 7823903
TI  - Variegation patterns caused by excision of the maize transposable element
      Dissociation (Ds) are autonomously regulated by allele-specific Activator (Ac)
      elements and are not due to trans-acting modifier genes.
AB  - The Ac elements present in the unstable wx-m7 and wx-m9 alleles of maize trigger
      different patterns of Ds excision in trans. To determine whether this
      differential regulation is a feature of the Ac alleles themselves or is mediated
      by genetically distinct factors, maize plants heterozygous for the wx-m7 and wx
      m9 alleles were crossed to tester strains homozygous for Ds reporter alleles.
      Kernels showing the variegation pattern characteristic for the Ac elements
      carried in the wx-m7 and wx-m9 alleles were found to be present in the ratios
      expected from the genetic constitution of the strains. The aleurone variegation
      caused by excision of the Ds reporter element and the endosperm variegation
      caused by excision of Ac from the wx-m7 and wx-m9 alleles themselves segregated
      with the original wx-m alleles. In addition, stable Wx and wx derivatives of wx
      m9 that have lost Ac no longer exert any trans effect on the wx-m7 allele (and
      vice versa). Therefore it is concluded that the observed variegation patterns are
      autonomously determined by specific trans effects of the particular Ac element.

PMID- 7823904
TI  - Abscisic acid-dependent and -independent regulation of gene expression by
      progressive drought in Arabidopsis thaliana.
AB  - Four clones corresponding to Arabidopsis thaliana transcripts regulated by
      progressive drought stress were isolated. Abundance of the AtDi8, AtDi19 and
      AtDi21 mRNAs increased in both roots and leaves during progressive drought. The
      AtDr4 mRNA was expressed in a root-specific manner in regularly watered plants,
      and became undetectable under drought conditions. In all cases, the drought
      induced modifications of mRNA abundance could be reversed by subsequent
      rehydration. The predicted AtDr4 protein displays extensive similarity to various
      members of the Kunitz protein family, suggesting that AtDr4 might be a root
      specific protease inhibitor. Of these four genes, only AtDi8 and AtDi21 responded
      to an exogenous supply of abscisic acid (ABA). Analysis of the ABA-deficient aba
      mutant demonstrated that endogenous ABA indeed participates in the drought
      regulation of these two transcripts. This ABA-dependent response was
      differentially affected in the various classes of ABA-insensitive Arabidopsis
      mutants. The AtDi19 and AtDr4 mRNAs both responded to drought in an ABA
      independent manner, but at distinct thresholds of the progressive drought stress.
      Regulation of these four target genes by progressive drought stress thus appears
      to be mediated by at least three distinct signals, only one of which is ABA.

PMID- 7823905
TI  - Expression of a cytochrome P450 gene family in maize.
AB  - Maize seedlings, like seedlings of many other plants, are rich in cytochrome P450
      (P450) enzyme activity. Four P450 genes (CYPzm1-4), isolated from a seedling
      specific cDNA library, are characterized by a transient and seedling-specific
      expression pattern. The maximum steady state mRNA levels are reached at 3 days in
      root and at 7 days in shoot tissue, respectively. All four genes belong to one
      gene family and are closely related to the CYP71 family of plant P450 genes,
      which includes the enzymes of the ripening avocado fruit (CYP71A1) and eggplant
      hypocotyls (CYP71A2, A3, A4). The expression of these related P450 genes in
      monocot and dicot plants indicates that these enzymes play a significant role in
      plants; however, the in vivo enzyme functions are unknown. The divergence of the
      four members of the maize gene family is sufficiently high to account for
      different substrate and/or reaction specificity. Although the general expression
      pattern of the four genes is identical, the maximum steady-state mRNA levels vary
      in different maize lines. In situ hybridisation reveals the highest mRNA levels
      in the coleoptile, the first developed leaflets, the ground tissue of the nodular
      complex, and in the cortex and pith of the region of cell division in the root.
      The mapping of the maize CYPzm genes shows that, as in animals, P450 genes of the
      same family can be clustered. The presence of the CYPzm gene cluster in maize
      argues for generation of distinct plant P450 gene families by gene duplication.

PMID- 7823906
TI  - Overexpression of two penicillin structural genes in Aspergillus nidulans.
AB  - We have placed two different penicillin structural genes from Aspergillus
      nidulans, ipnA (encoding isopenicillin N synthetase, IPNS) and acyA (encoding
      acyl-CoA:6-aminopenicillanic acid acyltransferase, AAT), under the control of the
      strong alcA promoter [alcA(p)]. Single copies of these transcriptional fusions
      were targeted to the same chromosomal location and conditions have been worked
      out which simultaneously allow induction of the alcA(p) and support penicillin
      biosynthesis. Transcriptional induction of the chimeric genes alcA(p)::ipnA or
      alcA(p)::acyA(cdna) in the relevant recombinant strains results in 10-fold higher
      levels of the ipnA or acyA transcripts than those resulting from transcription of
      the corresponding endogenous genes. This increase causes a 40-fold rise in IPNS
      activity or a 8-fold rise in AAT activity. Despite this rise in enzyme levels,
      forced expression of the ipnA gene results in only a modest increase in levels of
      exported penicillin, whereas forced expression of the acyA gene reduces
      penicillin production, showing that neither of these enzymes is rate-limiting for
      penicillin biosynthesis in A. nidulans. A genomic version of the alcA(p)::acyA
      fusion in which the acyA gene is interrupted by three small introns, is inducible
      by threonine to a lesser extent (as determined by both acyA mRNA levels and AAT
      enzyme levels) than the corresponding cDNA version, suggesting that processing of
      the introns present in the primary transcript may limit acyA expression.

PMID- 7823907
TI  - Genetic aspects of aromatic amino acid biosynthesis in Lactococcus lactis.
AB  - Polymerase chain reaction (PCR) primers designed from a multiple alignment of
      predicted amino acid sequences from bacterial aroA genes were used to amplify a
      fragment of Lactococcus lactis DNA. An 8 kb fragment was then cloned from a
      lambda library and the DNA sequence of a 4.4 kb region determined. This region
      was found to contain the genes tyrA, aroA, aroK, and pheA, which are involved in
      aromatic amino acid biosynthesis and folate metabolism. TyrA has been shown to be
      secreted and AroK also has a signal sequence, suggesting that these proteins have
      a secondary function, possibly in the transport of amino acids. The aroA gene
      from L. lactis has been shown to complement an E. coli mutant strain deficient in
      this gene. The arrangement of genes involved in aromatic amino acid biosynthesis
      in L. lactis appears to differ from that in other organisms.

PMID- 7823908
TI  - Twintrons are not unique to the Euglena chloroplast genome: structure and
      evolution of a plastome cpn60 gene from a cryptomonad.
AB  - Introns within introns (twintrons) are known only from the Euglena chloroplast
      genome. Twintrons are group II or III introns, into which another group II or III
      intron has been transposed. In this paper we describe a non-Euglena twintron
      structure within a plastid-encoded chaperone gene (cpn60) of the cryptomonad alga
      Pyrenomonas salina. In addition, the evolutionary relationships between members
      of the Cpn60 protein family are determined. Our findings permit the inclusion of
      cryptomonad plastomes in phylogenetic studies of intron evolution and present
      further evidence for the origin of modern plastids from a cyanobacterial
      ancestor.

PMID- 7823909
TI  - The transposable element impala, a fungal member of the Tc1-mariner superfamily.
AB  - A new transposable element has been isolated from an unstable niaD mutant of the
      fungus Fusarium oxysporum. This element, called impala, is 1280 nucleotides long
      and has inverted repeats of 27 bp. Impala inserts into a TA site and leaves
      behind a "foot-print" when it excises. The inserted element, impala-160, is cis
      active, but is probably trans-defective owing to several stop codons and
      frameshifts. Similarities exist between the inverted repeats of impala and those
      of transposons belonging to the widely dispersed mariner and Tc1 families.
      Moreover, translation of the open reading frame revealed three regions showing
      high similarities with Tc1 from Caenorhabditis elegans and with the mariner
      element of Drosophila mauritiana. The overall comparison shows that impala
      occupies an intermediate position between the mariner and Tc1-like elements,
      suggesting that all these elements belong to the same superfamily. The degree of
      relatedness observed between these elements, described in different kingdoms,
      raises the question of their origin and evolution.

PMID- 7823910
TI  - Molecular organization of Chlorella vulgaris chromosome I: presence of telomeric
      repeats that are conserved in higher plants.
AB  - The unicellular green alga Chlorella vulgaris (strain C-169) has a small genome
      (38.8 Mb) consisting of 16 chromosomes, which can be easily separated by CHEF gel
      electrophoresis. We have isolated and characterized the smallest chromosome
      (chromosome I, 980 kb) to elucidate the fundamental molecular organization of a
      plant-type chromosome. Restriction mapping and sequence analyses revealed that
      the telomeres of this chromosome consist of 5'-TTTAGGG repeats running from the
      centromere towards the termini; this sequence is identical to those reported for
      several higher plants. This sequence is reiterated approximately 70 times at both
      termini, although individual clones exhibited microheterogeneity in both sequence
      and copy number of the repeats. Subtelomeric sequences proximal to the termini
      were totally different from each other: on the left arm, unique sequence elements
      (14-20 bp) which were specific to chromosome I, form a repeat array of 1.7 kb,
      whereas a 1.0 kb sequence on the right arm contained a poly(A)-associated element
      immediately next to the telomeric repeats. This element is repeated several times
      on chromosome I and many times on all the other chromosomes of this organism.

PMID- 7823911
TI  - DNA amplifications and deletions in Streptomyces lividans 66 and the loss of one
      end of the linear chromosome.
AB  - Thirty-two 2-deoxygalactose-resistant mutants with DNA amplifications were
      isolated from Streptomyces lividans 66 strains carrying plasmid pMT664, which
      carries an agarase gene (dagA) and IS466. Thirty-one of the mutants carried
      amplified DNA sequences from a 70 kb region about 300 kb from one end of the
      linear chromosome in this species. In 28 of the mutants, all the wild-type
      sequences between the amplified region and the start of the 30 kb inverted repeat
      that forms the chromosome end were deleted. Thus, there appeared to be loss of
      one chromosome end and its replacement by the DNA amplification. In some mutants
      there amplification of a previously characterised 5.7 kb sequence that lies about
      600 kb from the other chromosome end was also noted.

PMID- 7823912
TI  - Molecular characterization of nucleotide sequences encoding the extracellular
      glycoprotein elicitor from Phytophthora megasperma.
AB  - cDNA sequences encoding the 42 kDa glycoprotein elicitor from the oomycete,
      Phytophthora megasperma, that induces the defense response in parsley have been
      cloned and sequenced. The 5' end of the mRNA matches a consensus derived from
      sequences surrounding the transcription initiation sites of seven other oomycete
      genes. The major transcript of 1802 nucleotides contains a 529-codon open reading
      frame, which was predicted to encode a 57 kDa precursor protein. On the basis of
      peptide sequencing, the N-terminus of the mature protein is at position 163,
      suggesting that proteolytic processing events, in addition to signal peptide
      cleavage, generate the protein purified from the fungal culture filtrate.
      Expression studies in Escherichia coli with the cDNA as well as smaller
      subfragments demonstrated that a region of 47 amino acids located in the C
      terminal third of the protein was sufficient to confer elicitor activity. The
      gene encoding the elicitor was found to be a member of a multigene family in P.
      megasperma. Homologous families of differing sizes were found in all eight other
      Phytophthora species tested, but not in other filamentous fungi including other
      Oomycetes. No significant similarity of the elicitor preprotein to sequences
      present in the databases has yet been detected.

PMID- 7823913
TI  - Ty1-copia group retrotransposon sequences in amphibia and reptilia.
AB  - We have isolated sequences belonging to Ty1-copia group retrotransposons from the
      genomes of an amphibian (Pyxicephalus adspersa) and three reptiles (Conolophus
      subscristatus, Amblyrynchus cristatus and Pytas mucosus). Two different sequences
      were found in the amphibian (Tpa1 and Tpa2). Each is present in several copies
      per genome and absent from the genomes of two other amphibian species. The C.
      subcristatus sequence Tcs1 is present in multiple copies in both its host genome
      (Galapagos land iguana) and the genome of the related Galapagos marine iguana (A.
      cristatus). There is little or no polymorphism in Tcs1 insertions between
      different individual animals, suggesting that this sequence is not transposing
      rapidly in either iguana genome. The P. mucosus sequence Tpm1 shows a
      discontinuous distribution in snake species, suggesting that it has either been
      lost from many lineages during vertical germline transmission or has been
      transferred horizontally in some snake species. Phylogenetic comparisons of all
      these sequences with each other and with other members of this retrotransposon
      group from other animals and plants show that sequences within a particular
      vertebrate species are most closely related to each other, consistent with a
      vertical transmission model for their evolution.

PMID- 7823914
TI  - Site-specific integration of the phage phi CTX genome into the Pseudomonas
      aeruginosa chromosome: characterization of the functional integrase gene located
      close to and upstream of attP.
AB  - The site-specific integration of the phage phi CTX genome, which carries the gene
      for a pore-forming cytotoxin, into the Pseudomonas aeruginosa chromosome was
      analysed. The 1,167 bp integrase gene, int, located immediately upstream of the
      attachment site, attP, was characterized using plasmid constructs, harbouring the
      integration functions, and serving as an integration probe in both P. aeruginosa
      and Escherichia coli. The attP plasmids p1000/p400 in the presence of the int
      plasmid pIBH and attP-int plasmids pINT/pINTS can be stably integrated into the
      P. aeruginosa chromosome. Successful recombination between the attP plasmid p1000
      and the attB plasmid p5.1, in the presence of the int plasmid pIBH in E. coli
      HB101 showed that the int gene is active in trans in E. coli. The int gene
      product was detected as a 43 kDa protein in E. coli maxicells harbouring pINT.
      Proposed integration arm regions downstream of attP are not necessary for the
      integration process. pINT and phage phi CTX could be integrated together into P.
      aeruginosa chromosomal DNA, yielding double integrates.

PMID- 7823915
TI  - A ste12 allele having a differential effect on a versus alpha cells.
AB  - The transcriptional activator Ste12p is a key component of the yeast pheromone
      response pathway: phosphorylated as a consequence of signal transduction, it
      activates transcription of genes that promote mating and the subsequent fusion of
      the two cell types a and alpha. Activation by Ste12p requires three types of
      protein-protein interaction between DNA-binding activator proteins: (1) Ste12p by
      itself can induce non-cell-type-specific genes involved in mating; (2)
      cooperation of the transactivator Mcm1p with Ste12p induces a-specific genes; and
      (3) formation of a complex of the activator proteins Mcm1p and alpha 1 (a
      transcriptional activator of alpha-specific genes) with Ste12p is believed to
      induce alpha-specific genes. We isolated and characterized a partially functional
      ste12 allele (ste12-T50), that is defective only in the activation of alpha
      specific genes. ste12-T50 was isolated as a second-site mutation conferring the a
      mating phenotype on mat alpha 2 mutant cells. In mat alpha 2 cells, where due to
      the lack of repressor, alpha 2, both sets of cell-type-specific genes are
      expressed, ste12-T50 apparently tips the balance in favor of a-specific gene
      expression. Thus, mat alpha 2 ste12-T50 cells mate like a cells. Additional ste12
      mutants that confer the a mating phenotype on mat alpha 2 cells have also been
      isolated.

PMID- 7823917
TI  - Domain analysis of the plant DNA-binding protein GT1a: requirement of four
      putative alpha-helices for DNA binding and identification of a novel
      oligomerization region.
AB  - Light is an important environmental signal that can influence diverse
      developmental processes in plants. Many plant nuclear genes respond to light at
      the level of transcription initiation. GT-1 and GT2 are nuclear factors which
      interact with DNA sequences in many light-responsive gene promoters. cDNA clones
      which encode proteins with sequence binding specificities similar to those of
      these two factors have been isolated. They show significant amino acid sequence
      similarities within three closely spaced, putative alpha-helices that were
      predicted by secondary structure analysis but do not show significant homologies
      with any other reported DNA-binding protein. In this work, N- and C-terminal
      deletions of tobacco GT1a were generated by in vitro transcription and
      translation, and their DNA-binding activities and subunit structures were
      studied. The results suggest that the C-terminal domain of GT1a is critical for
      protein oligomerization, while a region predicted to contain four closely spaced
      alpha-helices is required for DNA binding. Direct chemical cross-linking and gel
      filtration analyses of full-length and truncated derivatives of GT1a suggest that
      this factor can exist in solution as a homotetramer and that oligomerization is
      independent of DNA binding. This study thus establishes two independent
      functional domains in this class of eukaryotic trans-acting factors. Possible
      implications of the multimeric nature of GT1a in relation to the known
      characteristics of light-responsive promoter architecture are discussed.

PMID- 7823916
TI  - Hormone-independent repression of AP-1-inducible collagenase promoter activity by
      glucocorticoid receptors.
AB  - The role of the ligand in glucocorticoid receptor-mediated transactivation and
      transrepression of gene expression was investigated. Half-maximal transactivation
      of a mouse mammary tumor virus-chloramphenicol acetyltransferase reporter gene in
      transfected cells expressing the human glucocorticoid receptor mutant GRL753F,
      from which the rate of ligand dissociation is four to five times higher than the
      rate of dissociation from normal receptors, required a 200- to 300-fold-higher
      concentration of dexamethasone than was required in cells expressing the normal
      receptor. Immunocytochemical analysis demonstrated that this difference was not
      the result of a failure of the mutant receptor to accumulate in the nucleus after
      steroid treatment. In contrast, in cells cotransfected with a reporter gene
      containing the AP-1-inducible collagenase gene promoter, the concentration of
      dexamethasone required for 50% transrepression was the same for mutant and normal
      receptors. Efficient receptor-mediated transrepression was also observed with the
      double mutant GRL753F/C421Y, in which the first cysteine residue of the proximal
      zinc finger has been replaced by tyrosine, indicating that neither retention of
      the ligand nor direct binding of the receptor to DNA is required. RU38486 behaved
      as a full agonist with respect to transrepression. In addition, receptor
      dependent transrepression, but not transactivation, was observed in transfected
      cells after heat shock in the absence of the ligand. Taken together, these
      results suggest that unlike transactivation, transrepression of AP-1 activity by
      the nuclear glucocorticoid receptor is ligand independent.

PMID- 7823918
TI  - Initiation of translation can occur only in a restricted region of the CYC1 mRNA
      of Saccharomyces cerevisiae.
AB  - The steady-state levels and half-lives of CYC1 mRNAs were estimated in a series
      of mutant strains of Saccharomyces cerevisiae containing (i) TAA nonsense codons,
      (ii) ATG initiator codons, or (iii) the sequence ATA ATG ACT TAA (denoted ATG
      TAA) at various positions along the CYC1 gene, which encodes iso-1-cytochrome c.
      These mutational alterations were made in backgrounds lacking all internal in
      frame and out-of-frame ATG triplets or containing only one ATG initiator codon at
      the normal position. The results revealed a "sensitive" region encompassing
      approximately the first half of the CYC1 mRNA, in which nonsense codons caused
      Upf1-dependent degradation. This result and the stability of CYC1 mRNAs lacking
      all ATG triplets, as well as other results, suggested that degradation occurs
      unless elements associated with this sensitive region are covered with 80S
      ribosomes, 40S ribosomal subunits, or ribonucleoprotein particle proteins. While
      elongation by 80S ribosomes could be prematurely terminated by TAA codons, the
      scanning of 40S ribosomal units could not be terminated solely by TAA codons but
      could be disrupted by the ATG-TAA sequence, which caused the formation and
      subsequent prompt release of 80S ribosomes. The ATG-TAA sequence caused
      degradation of the CYC1 mRNA only when it was in the region spanning nucleotide
      positions -27 to +37 but not in the remaining 3' distal region, suggesting that
      translation could initiate only in this restricted initiation region. CYC1 mRNA
      distribution on polyribosomes confirmed that only ATG codons within the
      initiation region were translated at high efficiency. This initiation region was
      not entirely dependent on the distance from the 5' cap site and was not obviously
      dependent on the short-range secondary structure but may simply reflect an open
      structural requirement for initiation of translation of the CYC1 mRNA.

PMID- 7823919
TI  - A dynamic balance between ARP-1/COUP-TFII, EAR-3/COUP-TFI, and retinoic acid
      receptor:retinoid X receptor heterodimers regulates Oct-3/4 expression in
      embryonal carcinoma cells.
AB  - The Oct-3/4 transcription factor is a member of the POU family of transcription
      factors and, as such, probably plays a crucial role in mammalian embryogenesis
      and differentiation. It is expressed in the earliest stages of embryogenesis and
      repressed in subsequent stages. Similarly, Oct-3/4 is expressed in embryonal
      carcinoma (EC) cells and is repressed in retinoic acid (RA)-differentiated EC
      cells. Previously we have shown that the Oct-3/4 promoter harbors an RA
      responsive element, RAREoct, which functions in EC cells as a binding site for
      positive regulators of transcription and in RA-differentiated EC cells as a
      binding site for positive regulators of transcription and in RA-differentiated EC
      cells as a binding site for negative regulators. Our present results demonstrate
      that in P19 and RA-treated P19 cells, the orphan receptors ARP-1/COUP-TFII and
      EAR-3/COUP-TFI repress Oct-3/4 promoter activity through the RAREoct site in a
      dose-dependent manner. While the N-terminal region of the ARP-1/COUP-TFII
      receptor is dispensable for this repression, the C-terminal domain harbors the
      silencing region. Interestingly, three different RA receptor:retinoid X receptor
      (RAR:RXR) heterodimers, RAR alpha:RXR alpha, RAR beta:RXR alpha, and RAR beta:RXR
      beta, specifically bind and activate Oct-3/4 promoter through the RAREoct site in
      a ligand-dependent manner. We have shown that antagonism between ARP-1/COUP-TFII
      or EAR-3/COUP-TFI and the RAR:RXR heterodimers and their intracellular balance
      modulate Oct-3/4 expression. Oct-3/4 transcriptional repression by the orphan
      receptors can be overcome by increasing amounts of RAR:RXR heterodimers.
      Conversely, activation of Oct-3/4 promoter by RAR:RXR heterodimers was completely
      abolished by EAR-3/COUP-TFI and by ARP-1/COUP-TFII. The orphan receptors bind the
      RAREoct site with a much higher affinity than the RAR:RXR heterodimers. This high
      binding affinity provides ARP-1/COUP-TFII and EAR-3/COUP-TFI with the ability to
      compete with and even displace RAR:RXR from the RAREoct site and subsequently to
      actively silence the Oct-3/4 promoter. We have shown that RA treatment of EC
      cells results in up-regulation of ARP-1/COUP-TFII and EAR-3/COUP-TFI expression.
      Most interestingly, in RA-treated EC cells, the kinetics of Oct-3/4 repression
      inversely correlates with the kinetics of ARP-1/COUP-TFII and EAR-3/COUP-TFI
      activation. These findings are in accordance with the suggestion that these
      orphan receptors participate in controlling a network of transcription factors,
      among which Oct-3/4 is included, which may establish the pattern of normal gene
      expression during development.

PMID- 7823920
TI  - A spectrum of mechanisms for the assembly of the RNA polymerase II transcription
      preinitiation complex.
AB  - To explore the diversity in the mechanisms of basal transcription by RNA
      polymerase II, we have employed a novel biochemical approach that involves
      perturbation of the transcription reaction with exogenously added TFIIB or TATA
      box-binding protein (TBP). Under these conditions, we observe promoter-selective
      inhibition of transcription by excess TFIIB or excess TBP. This inhibition occurs
      at the level of basal transcription, because it is observed with minimal
      promoters that comprise only the TATA box and initiation site sequences as well
      as with preparations of basal transcription factors that have been purified to
      greater than 90% homogeneity. In addition, the excess basal factors inhibit the
      assembly of a functional preinitiation complex but do not inhibit transcription
      initiation from preassembled preinitiation complexes. A study of several
      promoters revealed a reciprocal trend in the promoter specificity of inhibition
      by excess TFIIB versus that by excess TBP. At opposite ends of this spectrum,
      promoters are strongly inhibited by excess TFIIB but not excess TBP and vice
      versa. These results reveal the existence of a spectrum of mechanisms for
      preinitiation complex assembly at different promoters. The mechanistic preference
      appears to be specified by the aggregate of basal promoter elements rather than
      by an individual component, such as the TATA box or initiation site sequence.
      This spectrum provides a new parameter by which differences in the function of
      minimal class II promoters can be analyzed in the context of both basal and
      regulated transcription.

PMID- 7823921
TI  - Modulation of p53-mediated transcriptional repression and apoptosis by the
      adenovirus E1B 19K protein.
AB  - BRK cell lines that stably express adenovirus E1A and a murine temperature
      sensitive p53 undergo apoptosis when p53 assumes the wild-type conformation.
      Expression of the E1B 19,000-molecular-weight (19K) protein rescues cells from
      this p53-mediated apoptosis and diverts cells to a growth-arrested state. As p53
      likely functions as a tumor suppressor by regulating transcription, the ability
      of the E1B 19K protein to regulate p53-mediated transactivation and
      transcriptional repression was investigated. In promoter-reporter assays the E1B
      19K did not block p53-mediated transactivation but did alleviate p53-mediated
      transcriptional repression. E1B 19K expression permitted efficient
      transcriptional activation of the p21/WAF-1/cip-1 mRNA by p53, consistent with
      maintenance of the growth arrest function of p53. The E1B 19K protein is thereby
      unique among DNA virus-transforming proteins that target p53 for inactivation in
      that it selectively modulates the transcriptional properties of p53. The E1B 19K
      protein also rescued cells from apoptosis induced by inhibitors of transcription
      and protein synthesis. This suggests that cell death may result from the
      inhibition of expression of survival factors which function to maintain cell
      viability. p53 may induce apoptosis through generalized transcriptional
      repression. In turn, the E1B 19K protein may prevent p53-mediated apoptosis by
      alleviating p53-mediated transcriptional repression.

PMID- 7823922
TI  - In vivo growth of a murine lymphoma cell line alters regulation of expression of
      HSP72.
AB  - We have identified a murine B-cell lymphoma cell line, CH1, that has a much
      diminished capacity to express increased levels of heat shock proteins in
      response to heat stress in vitro. In particular, these cells cannot synthesize
      the inducible 72-kDa heat shock protein (HSP72) which is normally expressed at
      high levels in stressed cells. We show here that CH1 fails to transcribe HSP72
      mRNA after heat shock, even though the heat shock transcription factor, HSF, is
      activated correctly. After heat shock, HSF from CH1 is found in the nucleus and
      is phosphorylated, trimerized, and capable of binding the heat shock element. We
      propose that additional signals which CH1 cells are unable to transduce are
      normally required to activate hsp72 transcription in vitro. Surprisingly, we have
      found that when the CH1 cells are heated in situ in a mouse, they show normal
      expression of HSP72 mRNA and protein. Therefore, CH1 cells have a functional
      hsp72 gene which can be transcribed and translated when the cells are in an
      appropriate environment. A diffusible factor present in ascites fluid is capable
      of restoring normal HSP72 induction in CH1 cells. We conclude that as-yet
      undefined factors are required for regulation of the hsp72 gene or,
      alternatively, that heat shock in vivo causes activation of hsp70 through a novel
      pathway which the defect in CH1 has exposed and which is distinct from that
      operating in vitro. This unique system offers an opportunity to study a
      physiologically relevant pathway of heat shock induction and to biochemically
      define effectors involved in the mammalian stress response.

PMID- 7823923
TI  - The X protein of hepatitis B virus coactivates potent activation domains.
AB  - Transactivation by hepatitis B virus X protein (pX) is promiscuous, but it
      requires cellular activators. To study the mode of action of pX, we coexpressed
      pX with Gal4-derived activators in a cotransfection system. Twelve different
      activators bearing different types of activation domains were compared for their
      response to pX. Because pX indirectly increases the amount of the activators,
      tools were developed to compare samples with equivalent amount of activators. We
      demonstrate that pX preferentially coactivates potent activators, especially
      those with acidic activation domains. Weak activators with nonacidic activation
      domains are not potentiated by pX. Interestingly, Gal4E1a, which is not rich in
      acidic residues but interacts with similar molecular targets, also responds to
      pX. The response to pX correlated with the strength of the activation domain.
      Collectively, these data imply that pX is a coactivator, which offers a molecular
      basis for the pleiotropic effects of pX on transcription.

PMID- 7823924
TI  - A ternary complex factor-dependent mechanism mediates induction of egr-1 through
      selective serum response elements following antigen receptor cross-linking in B
      lymphocytes.
AB  - Induction of the primary response gene egr-1 occurs rapidly following antigen
      receptor cross-linking in B lymphocytes. Antisense studies have demonstrated that
      this induction is necessary for their subsequent activation to this signal. The
      present study examines the molecular mechanism whereby the receptor-generated
      signals interact with the egr-1 promoter to elicit transcription. Deletion
      mapping and point mutations have indicated that two of the five serum response
      elements (SREs) in the egr-1 promoter can mediate induction. Of the two critical
      SREs, both are capable of mediating maximal induction even in the absence of the
      other SRE. Our results also indicate that adjacent Ets motifs are necessary for
      induction. Like the c-fos SRE, the egr-1 SRE/Ets sites are occupied by a
      multiprotein (ternary) complex containing a homodimer of serum response factor
      and an unidentified member of the Ets family of transcription factors. The
      identification of a ternary complex-dependent mechanism of egr-1 induction, along
      with selective utilization of SREs in B lymphocytes, suggests that a complicated
      array of signaling cascades interacts with unique combinations of regulatory
      elements in the egr-1 promoter in different cell types.

PMID- 7823925
TI  - Activation of intracellular kinases in Xenopus oocytes by p21ras and
      phospholipases: a comparative study.
AB  - Signal transduction induced by generations of second messengers from membrane
      phospholipids is a major regulatory mechanism in the control of cell
      proliferation. Indeed, oncogenic p21ras alters the intracellular levels of
      phospholipid metabolites in both mammalian cells and Xenopus oocytes. However, it
      is still controversial whether this alteration it is biologically significant. We
      have analyzed the ras-induced signal transduction pathway in Xenopus oocytes and
      have correlated its mechanism of activation with that of the three most relevant
      phospholipases (PLs). After microinjection, ras-p21 induces a rapid PLD
      activation followed by a late PLA2 activation. By contrast, phosphatidylcholine
      specific PLC was not activated under similar conditions. When each of these PLs
      was studied for its ability to activate intracellular signalling kinases, all of
      them were found to activate maturation-promoting factor efficiently. However,
      only PLD was able to activate MAP kinase and S6 kinase II, a similar pattern to
      that induced by p21ras proteins. Thus, the comparison of activated enzymes after
      microinjection of p21ras or PLs indicated that only PLD microinjection mimetized
      p21ras signalling. Finally, inhibition of the endogenous PLD activity by neomycin
      substantially reduced the biological activity of p21ras. All these results
      suggest that PLD activation may constitute a relevant step in ras-induced
      germinal vesicle breakdown in Xenopus oocytes.

PMID- 7823926
TI  - DNA synthesis induced by some but not all growth factors requires Src family
      protein tyrosine kinases.
AB  - The Src family of protein tyrosine kinases have been implicated in the response
      of cells to several ligands. These include platelet-derived growth factor (PDGF),
      epidermal growth factor (EGF), and colony stimulating factor type 1 (CSF-1, in
      macrophages and in fibroblasts engineered to express the receptor). We recently
      described a microinjection approach which we used to demonstrate that Src family
      kinases are required for PDGF-induced S phase entry of fibroblasts. We now use
      this approach to ask whether other ligands also require Src kinases to stimulate
      cells to replicate DNA. An antibody specific for the carboxy terminus of Src,
      Fyn, and Yes (anti-cst.1) inhibited Src kinase activity in vitro and caused
      morphological reversion of Src transformed cells in vivo. Microinjection of this
      antibody was used to demonstrate that Src kinases were required for both CSF-1
      and EGF to drive cells into the S phase. Expression of a kinase-inactive form of
      Src family kinases also prevented EGF- and CSF-1-stimulated DNA synthesis.
      However, even though the Src family kinases were necessary for both PDGF- and EGF
      induced DNA synthesis in Swiss 3T3 cells, the responses to two other potent
      growth factors for these cells, lysophosphatidic acid and bombesin, were
      unaffected by the neutralizing antibodies. Therefore, some but not all growth
      factors required functional Src family kinases to transmit mitogenic responses.

PMID- 7823927
TI  - Regulation of scatter factor/hepatocyte growth factor responses by Ras, Rac, and
      Rho in MDCK cells.
AB  - Scatter factor/hepatocyte growth factor (SF/HGF) stimulates the motility of
      epithelial cells, initially inducing centrifugal spreading of cell colonies
      followed by disruption of cell-cell junctions and subsequent cell scattering.
      These responses are accompanied by changes in the actin cytoskeleton, including
      increased membrane ruffling and lamellipodium extension, disappearance of
      peripheral actin bundles at the edges of colonies, and an overall decrease in
      stress fibers. The roles of the small GTP-binding proteins Ras, Rac, and Rho in
      regulating responses to SF/HGF were investigated by microinjection. Inhibition of
      endogenous Ras proteins prevented SF/HGF-induced actin reorganization, spreading,
      and scattering, whereas microinjection of activated H-Ras protein stimulated
      spreading and actin reorganization but not scattering. When a dominant inhibitor
      of Rac was injected, SF/HGF- and Ras-induced spreading and actin reorganization
      were prevented, although activated Rac alone did not stimulate either response.
      Microinjection of activated Rho inhibited spreading and scattering, while
      inhibition of Rho function led to the disappearance of stress fibers and
      peripheral bundles but did not prevent SF/HGF-induced motility. We conclude that
      Ras and Rac act downstream of the SF/HGF receptor p190Met to mediate cell
      spreading but that an additional signal is required to induce scattering.

PMID- 7823928
TI  - Dissecting a locus control region: facilitation of enhancer function by extended
      enhancer-flanking sequences.
AB  - Using transgenic mice, we have defined novel gene regulatory elements, termed
      "facilitators." These elements bilaterally flank, by up to 1 kb, a 200-bp T-cell
      specific enhancer domain in the human adenosine deaminase (ADA) gene.
      Facilitators were essential for gene copy-proportional and integration site
      independent reporter expression in transgenic thymocytes, but they had no effect
      on the enhancer in transfected T cells. Both segments were required. Individual
      segments had no activity. A lack of facilitator function caused positional
      susceptibility and prevented DNase I-hypersensitive site formation at the
      enhancer. The segments were required to be at opposed ends of the enhancer, and
      they could not be grouped together. Reversing the orientation of a facilitator
      segment caused a partial loss of function, suggesting involvement of a
      stereospecific chromatin structure. trans-acting factor access to enhancer
      elements was modeled by exposing nuclei to a restriction endonuclease. The
      enhancer domain was accessible to the 4-cutter DpnII in a tissue- and cell-type
      specific fashion. However, unlike DNase I hypersensitivity and gene expression,
      accessibility to the endonuclease could occur without the facilitator segments,
      suggesting that an accessible chromatin domain is an intermediate state in the
      activational pathway. These results suggest that facilitators (i) are distinct
      from yet positionally constrained to the enhancer, (ii) participate in a
      chromatin structure transition that is necessary for the DNase I hypersensitivity
      and the transcriptional activating function of the enhancer, and (iii) act after
      cell-type-specific accessibility to the enhancer sequences is established by
      factors that do not require the facilitators to be present.

PMID- 7823929
TI  - PHR1, a pH-regulated gene of Candida albicans, is required for morphogenesis.
AB  - Candida albicans, like many fungi, exhibits morphological plasticity, a property
      which may be related to its biological capacity as an opportunistic pathogen of
      humans. Morphogenesis and alterations in cell shape require integration of many
      cellular functions and occur in response to environmental signals, most notably
      pH and temperature in the case of C. albicans. In the course of our studies of
      differential gene expression associated with dimorphism of C. albicans, we have
      isolated a gene, designated PHR1, which is regulated in response to the pH of the
      culture medium. PHR1 expression was repressed at pH values below 5.5 and induced
      at more alkaline pH. The predicted amino acid sequence of the PHR1 protein was
      56% identical to that of the Saccharomyces cerevisiae Ggp1/Gas1 protein, a highly
      glycosylated cell surface protein attached to the membrane via
      glycosylphosphatidylinositol. A homozygous null mutant of PHR1 was constructed
      and found to exhibit a pH-conditional morphological defect. At alkaline pH, the
      mutant, unlike the parental type, was unable to conduct apical growth of either
      yeast or hyphal growth forms. This morphological aberration was not associated
      with defective cytoskeletal polarization or secretion. The results suggest that
      PHR1 defines a novel function required for apical cell growth and morphogenesis.

PMID- 7823930
TI  - The receptor tyrosine kinase ARK mediates cell aggregation by homophilic binding.
AB  - The ARK (AXL, UFO) receptor is a member of a new family of receptor tyrosine
      kinases whose extracellular domain contains a combination of fibronectin type III
      and immunoglobulin motifs similar to those found in many cell adhesion molecules.
      ARK mRNA is expressed at high levels in the mouse brain, prevalently in the
      hippocampus and cerebellum, and this pattern of expression resembles that of
      adhesion molecules that are capable of promoting cell aggregation through
      homophilic or heterophilic binding. We report here the ability of the murine ARK
      receptor to mediate homophilic binding. Expression of the ARK protein in
      Drosophila S2 cells induces formation of cell aggregates consisting of ARK
      expressing cells, and aggregation leads to receptor activation, with an increase
      in receptor phosphorylation. Homophilic binding does not require ARK tyrosine
      kinase activity, since S2 cells expressing a receptor in which the intracellular
      domain was deleted were able to undergo aggregation as well as cells expressing
      the wild-type ARK receptor. Similar results were obtained with NIH 3T3 and CHO
      cells expressing high levels of ARK, although in this case ARK expression
      appeared to be accompanied by constitutive activation. The purified recombinant
      extracellular domain of ARK can induce homotypic aggregation of coated
      fluorescent beads (Covaspheres), and this protein can also function as a
      substrate for adhesion by S2 and NIH 3T3 cells expressing ARK. These results
      suggest that ARK represents a new cell adhesion molecule that through its
      homophilic interaction may regulate cellular functions during cell recognition.

PMID- 7823931
TI  - Rescue of GATA-1-deficient embryonic stem cells by heterologous GATA-binding
      proteins.
AB  - Totipotent murine embryonic stem (ES) cells can be differentiated in vitro to
      form embryoid bodies (EBs) containing hematopoietic cells of multiple lineages,
      including erythroid cells. In vitro erythroid development parallels that which is
      observed in vivo. ES cells in which the gene for the erythroid transcription
      factor GATA-1 has been disrupted fail to produce mature erythroid cells either in
      vivo or in vitro. With the EB in vitro differentiation assay, constructs
      expressing heterologous GATA-binding proteins were tested for their abilities to
      correct the developmental defect of GATA-1-deficient ES cells. The results
      presented here show that the highly divergent chicken GATA-1 can rescue GATA-1
      deficiency to an extent similar to that of murine GATA-1 (mGATA-1), as determined
      by size and morphology of EBs, presence of red cells, and globin gene expression.
      Furthermore, GATA-3 and GATA-4, which are normally expressed in different
      tissues, and a protein consisting of the zinc fingers of GATA-1 fused to the
      herpes simplex virus VP16 transcription activation domain were able to compensate
      for the GATA-1 defect. Chimeric molecules in which both zinc fingers of mGATA-1
      were replaced with the zinc fingers of human GATA-3 or with the single finger of
      the fungal GATA factor areA, as well as a construct bearing the zinc finger
      region alone, displayed rescue activity. These results suggest that neither the
      transcription activation domains of mGATA-1 nor its zinc fingers impart erythroid
      cell specificity for its action in vivo. Rather, it appears that specificity is
      mediated through the cis-acting control regions which determine spatial and
      temporal expression of the GATA-1 gene. Furthermore, our results demonstrate that
      the zinc finger region may have a biological function in addition to mediating
      DNA binding.

PMID- 7823932
TI  - The C-terminal zinc finger of GATA-1 or GATA-2 is sufficient to induce
      megakaryocytic differentiation of an early myeloid cell line.
AB  - The GATA-1 and GATA-2 transcription factors, which each contain two homologous
      zinc fingers, are important hematopoietic regulators expressed within the
      erythroid, mast cell, and megakaryocytic lineages. Enforced expression of either
      factor in the primitive myeloid line 416B induces megakaryocytic differentiation.
      The features of their structure required for this activity have been explored.
      The ability of 12 GATA-1 mutants to promote 416B maturation was compared with
      their DNA-binding activity and transactivation potential. Differentiation did not
      require any of the seven serine residues that are phosphorylated in vivo, an N
      terminal region bearing the major transactivation domain, or a C-terminal segment
      beyond the fingers. Removal of a consensus nuclear localization signal following
      the second finger did not block differentiation or nuclear translocation. The N
      terminal finger was also dispensable, although its removal attenuated
      differentiation. In contrast, the C-terminal finger was essential, underscoring
      its distinct function. Remarkably, only 69 residues spanning the C-terminal
      finger were required to induce limited megakaryocytic differentiation. Analysis
      of three GATA-2 mutants led to the same conclusion. Endogenous GATA-1 mRNA was
      induced by most mutants and may contribute to differentiation. Because the GATA-1
      C-terminal finger could bind its target site but not transactivate a minimal
      reporter, it may direct megakaryocytic maturation by derepressing specific genes
      and/or by interacting with another protein which provides the transactivation
      function.

PMID- 7823933
TI  - Developmental control of transcription of a retina-specific gene, QR1, during
      differentiation: involvement of factors from the POU family.
AB  - Developmental control of gene expression often results from the coupling of
      growth arrest with the establishment of differentiation programs. QR1 is a gene
      specifically expressed in retinas during the late phase of embryogenesis. At this
      stage neuroectodermal precursors have reached terminal mitosis and are undergoing
      differentiation into distinct cell types. Transcription of the QR1 gene is
      tightly regulated during retinal development: this gene is expressed between
      embryonic day 9 (ED9) and ED17 and is completely repressed at hatching in quail.
      Moreover, QR1 transcription is downregulated when postmitotic neural retina cells
      are induced to proliferate by pp60v-src. We studied the stage-dependent
      transcriptional control of this gene during quail neural retina (QNR) cell
      development. Transient transfection experiments with QR1/CAT constructs at
      various stages of development showed that a region located between -935 and -1265
      bp upstream of the transcription start site is necessary to promote transcription
      in retina cells during the late phase of embryonal development (QNR9,
      corresponding to ED9). By in vivo footprinting assays we identified at least two
      elements that are occupied by DNA-protein complexes in QNR cells: the A and B
      boxes. The A box allows formation of several biochemically distinct complexes:
      C1, C2, C3, and C4. Formation of the C2 complex mainly during early stages (ED7)
      and of C2, C3, and C4 complexes during postnatal life correlates with repression
      of QR1 transcription, whereas the C1 complex is strongly induced at ED11 when the
      QR1 gene is expressed. We previously showed that C1 was involved in
      downregulation of QR1 transcription by pp60v-src. Several complexes are also
      formed on the B box. We show that these complexes are exclusively present in
      neural tissues and that they involve members of the POU family of transcription
      factors. Mutations of each one of the two regions which abolish the binding of
      the C1 factor(s) on the A box and of the POU factor(s) on the B box also prevent
      stimulation of QR1 transcription in QNR9. Therefore, both elements appear to be
      required for the stage-specific transcription of the QR1 gene. We also show that
      the regulatory region from position -1265 to position -935 is able to confer
      stage-specific transcription upon a heterologous promoter (thymidine kinase).
      Indeed, this region stimulates transcription in differentiating retinas (QNR9)
      and represses transcription in terminally differentiated retinas (QNR17,
      corresponding to postnatal life). Our results suggest that cell growth regulation
      and developmental control are coordinated through the A and B boxes in regulating
      QR1 transcription during retinal differentiation.

PMID- 7823934
TI  - Transcriptional regulation of the mouse alpha A-crystallin gene: activation
      dependent on a cyclic AMP-responsive element (DE1/CRE) and a Pax-6-binding site.
AB  - Two cis-acting promoter elements (-108 to -100 and -49 to -33) of the mouse alpha
      A-crystallin gene, which is highly expressed in the ocular lens, were studied.
      Here we show that DE1 (-108 to -100; 5'TGACGGTG3'), which resembles the consensus
      cyclic AMP (cAMP)-responsive element sequence (CRE; 5'TGACGT[A/C][A/G]3'),
      behaves like a functional CRE site. Transfection experiments and electrophoretic
      mobility shift assays (EMSAs) using site-specific mutations correlated a loss of
      function with deviations from the CRE consensus sequence. Results of EMSAs in the
      presence of antisera against CREB, delta CREB, and CREM were consistent with the
      binding of CREB-like proteins to the DE1 sequence. Stimulation of alpha A
      crystallin promoter activity via 8-bromo-cAMP, forskolin, or human T-cell
      leukemia virus type I Tax1 in transfections and reduction of activity of this
      site in cell-free transcription tests by competition with the somatostatin CRE
      supported the idea that DE1 is a functional CRE. Finally, Pax-6, a member of the
      paired-box family of transcription factors, activated the mouse alpha A
      crystallin promoter in cotransfected COP-8 fibroblasts and bound to the -59 to 
      29 promoter sequence in EMSAs. These data provide evidence for a synergistic role
      of Pax-6 and CREB-like proteins for high expression of the mouse alpha A
      crystallin gene in the lens.

PMID- 7823936
TI  - Inversions produced during V(D)J rearrangement at IgH, the immunoglobulin heavy
      chain locus.
AB  - Diversity in immunoglobulin antigen receptors is generated in part by V(D)J
      recombination. In this process, different combinations of gene elements are
      joined in various configurations. Products of V(D)J recombination are coding
      joints, signal joints, and hybrid junctions, which are generated by deletion or
      inversion. To determine their role in the generation of diversity, we have
      examined two sorts of recombination products, coding joints and hybrid junctions,
      that have formed by inversion at the mouse immunoglobulin heavy-chain locus. We
      developed a PCR assay for quantification and characterization of inverted
      rearrangements of DH and JH gene elements. In primary cells from adult mice,
      inverted DJH rearrangements are detectable but they are rare. There were
      approximately 1,100 to 2,200 inverted DJH coding joints and inverted DJH hybrid
      junctions in the marrow of one adult mouse femur. On day 16 of gestation,
      inverted DJH rearrangements are more abundant. There are approximately 20,000
      inverted DJH coding joints and inverted DJH hybrid junctions per day 16 fetal
      liver. In fetal liver cells, the number of inverted DJH rearrangements remains
      relatively constant from day 14 to day 16 of gestation. Inverted DJH
      rearrangements to JH4, the most 3' JH element, are more frequently detected than
      inverted DJH rearrangements to other JH elements. We compare the frequencies of
      inverted DJH rearrangements to previously determined frequencies of uninverted
      DJH rearrangements (DJH rearrangements formed by deletion). We suggest that
      inverted DJH rearrangements are influenced by V(D)J recombination mechanistic
      constraints and cellular selection.

PMID- 7823935
TI  - Phosphorylation of rat liver heterogeneous nuclear ribonucleoproteins A2 and C
      can be modulated by calmodulin.
AB  - It was previously reported that the phosphorylation of three proteins of 36, 40
      to 42, and 50 kDa by casein kinase 2 is inhibited by calmodulin in nuclear
      extracts from rat liver cells (R. Bosser, R. Aligue, D. Guerini, N. Agell, E.
      Carafoli, and O. Bachs, J. Biol. Chem. 268:15477-15483, 1993). By immunoblotting,
      peptide mapping, and endogenous phosphorylation experiments, the 36- and 40- to
      42-kDa proteins have been identified as the A2 and C proteins, respectively, of
      the heterogeneous nuclear ribonucleoprotein particles. To better understand the
      mechanism by which calmodulin inhibits the phosphorylation of these proteins,
      they were purified by using single-stranded DNA chromatography, and the effect of
      calmodulin on their phosphorylation by casein kinase 2 was analyzed. Results
      revealed that whereas calmodulin inhibited the phosphorylation of purified A2 and
      C proteins in a Ca(2+)-dependent manner, it did not affect the casein kinase 2
      phosphorylation of a different protein substrate, i.e., beta-casein. These
      results indicate that the effect of calmodulin was not on casein kinase 2
      activity but on specific protein substrates. The finding that the A2 and C
      proteins can bind to a calmodulin-Sepharose column in a Ca(2+)-dependent manner
      suggests that this association could prevent the phosphorylation of the proteins
      by casein kinase 2. Immunoelectron microscopy studies have revealed that such
      interactions could also occur in vivo, since calmodulin and A2 and C proteins
      colocalize on the ribonucleoprotein particles in rat liver cell nuclei.

PMID- 7823937
TI  - The zinc finger transcription factor EGR-1 impedes interleukin-1-inducible tumor
      growth arrest.
AB  - Interleukin-1 (IL-1) is a growth arrest signal for diverse human tumor cell
      lines. We report here that the action of this cytokine in melanoma cells is
      associated with induction of EGR-1, a zinc finger protein that activates gene
      transcription. Both growth arrest and EGR-1 are induced via the type I receptor
      of IL-1. To determine the role of EGR-1 in IL-1 action in melanoma cells, we used
      a chimera expressing the transrepression domain of the Wilm's tumor gene, WT1,
      and the DNA binding domain of Egr-1. This chimera competitively inhibited EGR-1
      dependent transactivation via the GC-rich DNA binding sequence, indicating that
      it acted as a functional dominant negative mutant of Egr-1. Melanoma cell lines
      stably transfected with the dominant negative mutant construct were
      supersensitive to IL-1 and showed accelerated G0/G1 growth arrest compared with
      the parental cell line. The effect of the dominant negative mutant construct was
      mimicked by addition of an antisense Egr-1 oligomer to the culture medium of the
      parental cells: the oligomer inhibited EGR-1 expression and accelerated the
      growth-inhibitory response to IL-1. These data imply that EGR-1 acts to delay IL
      1-mediated tumor growth arrest.

PMID- 7823938
TI  - Alterations in differentiation and behavior of monocytic phagocytes in transgenic
      mice that express dominant suppressors of ras signaling.
AB  - To address the role of ras signaling in monocytic phagocytes in vivo, the
      expression of two dominant suppressors of in vitro ras signaling pathways, the
      carboxyl-terminal region of the GTPase-activating protein (GAP-C) and the DNA
      binding domain of the transcription factor ets-2, were targeted to this cell
      compartment. A 5-kb portion of the human c-fms proximal promoter was shown to
      direct expression of the transgenes to the monocytic lineage. As a result of the
      GAP-C transgene expression, ras-GTP levels were reduced in mature peritoneal
      macrophages by 70%. The terminal differentiation of monocytes was altered, as
      evidence by the accumulation of atypical monocytic cells in the blood. Mature
      peritoneal macrophages exhibited changes in colony-stimulating factor 1-dependent
      survival and structure. Further, expression of the colony-stimulating factor 1
      stimulated gene urokinase plasminogen activator was inhibited in peritoneal
      macrophages. The results indicate that ras action is critical in monocytic cells
      after these cells have lost the capacity to traverse the cell cycle.

PMID- 7823939
TI  - Expression cloning of oncogenes by retroviral transfer of cDNA libraries.
AB  - a cDNA library transfer system based on retroviral vectors has been developed for
      expression cloning in mammalian cells. The use of retroviral vectors results in
      stable cDNA transfer efficiencies which are at least 100-fold higher than those
      achieved by transfection and therefore enables the transfer and functional
      screening of very large libraries. In our initial application of retroviral
      transfer of cDNA libraries, we have selected for cDNAs which induce oncogenic
      transformation of NIH 3T3 fibroblasts, as measured by loss of contact inhibition
      of proliferation. Nineteen different transforming cDNAs were isolated from a
      total of 300,000 transferred cDNA clones. Three of these cDNAs were derived from
      known oncogenes (raf-1, lck, and ect2), while nine others were derived from genes
      which had been cloned previously but were not known to have the ability to
      transform fibroblasts (beta-catenin, thrombin receptor, phospholipase C-gamma 2
      and Spi-2 protease inhibitor genes). The Spi-2 cDNA was expressed in antisense
      orientation and therefore is likely to act as an inhibitor of an endogenous
      transformation suppressor. Seven novel cDNAs with transforming activities,
      including those for three new members of the CDC24 family of guanine nucleotide
      exchange factors, were also cloned from the retroviral cDNA libraries. Retroviral
      transfer of libraries should be generally useful for cloning cDNAs which confer
      selectable phenotypes on many different types of mammalian cells.

PMID- 7823940
TI  - AFR1 promotes polarized apical morphogenesis in Saccharomyces cerevisiae.
AB  - The G protein-coupled alpha-factor receptor promotes polarized growth toward a
      mating partner. alpha-Factor induces the expression of AFR1, which acts together
      with the receptor C terminus to promote normal morphogenesis. The function of
      AFR1 was investigated by engineering cells to constitutively express AFR1 without
      alpha-factor. Constitutive AFR1 expression caused cells to form elongated buds
      that demonstrate that AFR1 can also interact with the morphogenesis components
      that promote bud formation. A similar elongated bud phenotype is caused by
      mutation of the CDC3, CDC10, CDC11, and CDC12 genes, which encode putative
      filament proteins that form a ring at the bud neck. AFR1 may act directly on the
      filament proteins, since immunolocalization detected AFR1 at the bud neck and
      interaction of AFR1 and CDC12 was detected in the two-hybrid protein assay. AFR1
      localized to the base of pheromone-induced projections. These results suggest
      that AFR1 and the putative filament proteins act together with the receptor to
      facilitate proper localization of components during mating.

PMID- 7823941
TI  - p34Cdc28-mediated control of Cln3 cyclin degradation.
AB  - Cln3 cyclin of the budding yeast Saccharomyces cerevisiae is a key regulator of
      Start, a cell cycle event in G1 phase at which cells become committed to
      division. The time of Start is sensitive to Cln3 levels, which in turn depend on
      the balance between synthesis and rapid degradation. Here we report that the
      breakdown of Cln3 is ubiquitin dependent and involves the ubiquitin-conjugating
      enzyme Cdc34 (Ubc3). The C-terminal tail of Cln3 functions as a transferable
      signal for degradation. Sequences important for Cln3 degradation are spread
      throughout the tail and consist largely of PEST elements, which have been
      previously suggested to target certain proteins for rapid turnover. The Cln3 tail
      also appears to contain multiple phosphorylation sites, and both phosphorylation
      and degradation of Cln3 are deficient in a cdc28ts mutant at the nonpermissive
      temperature. A point mutation at Ser-468, which lies within a Cdc28 kinase
      consensus site, causes approximately fivefold stabilization of a Cln3-beta
      galactosidase fusion protein that contains a portion of the Cln3 tail and
      strongly reduces the phosphorylation of this protein. These data indicate that
      the degradation of Cln3 involves CDC28-dependent phosphorylation events.

PMID- 7823943
TI  - Distinct roles of the molecular chaperone hsp90 in modulating dioxin receptor
      function via the basic helix-loop-helix and PAS domains.
AB  - The intracellular dioxin receptor mediates signal transduction by dioxin and
      functions as a ligand-activated transcription factor. It contains a basic helix
      loop-helix (bHLH) motif contiguous with a Per-Arnt-Sim (PAS) homology region. In
      extracts from nonstimulated cells the receptor is recovered in an inducible
      cytoplasmic form associated with the 90-kDa heat shock protein (hsp90), a
      molecular chaperone. We have reconstituted ligand-dependent activation of the
      receptor to a DNA-binding form by using the dioxin receptor and its bHLH-PAS
      partner factor Arnt expressed by in vitro translation in reticulocyte lysate.
      Deletion of the PAS domain of the receptor resulted in constitutive dimerization
      with Arnt. In contrast, this receptor mutant showed low levels of xenobiotic
      response element-binding activity, indicating that the PAS domain may be
      important for DNA-binding affinity and/or specificity of the receptor. It was not
      possible to reconstitute dioxin receptor function with proteins expressed in
      wheat germ lysate. In line with these observations, reticulocyte lysate but not
      wheat germ lysate promoted the association of de novo synthesized dioxin receptor
      with hsp90. At least two distinct domains of the receptor mediated interaction
      with hsp90: the ligand-binding domain located within the PAS region and,
      surprisingly, the bHLH domain. Whereas ligand-binding activity correlated with
      association with hsp90, bHLH-hsp90 interaction appeared to be important for DNA
      binding activity but not for dimerization of the receptor. Several distinct roles
      for hsp90 in modulating dioxin receptor function are therefore likely: correct
      folding of the ligand-binding domain, interference with Arnt heterodimerization,
      and folding of a DNA-binding conformation of the bHLH domain. Thus, the dioxin
      receptor system provides a complex and interesting model of the regulation of
      transcription factors by hsp90.

PMID- 7823942
TI  - The transcription factor E2F-1 is a downstream target of RB action.
AB  - Reintroduction of RB into SAOS2 (RB-/-) cells causes a G1 arrest and
      characteristic cellular swelling. Coexpression of the cellular transcription
      factor E2F-1 could overcome these effects. The ability of E2F-1 to bind to RB was
      neither necessary nor sufficient for this effect, and S-phase entry was not
      accompanied by RB hyperphosphorylation under these conditions. Furthermore, E2F-1
      could overcome the actions of a nonphosphorylatable but otherwise intact RB
      mutant. These data, together with the fact that RB binds to E2F-1 in vivo,
      suggest that E2F-1 is a downstream target of RB action. Mutational analysis
      showed that the ability of E2F-1 to bind to DNA was necessary and sufficient to
      block the formation of large cells by RB, whereas the ability to induce S-phase
      entry required a functional transactivation domain as well. Thus, the induction
      of a G1 arrest and the formation of large cells by RB in these cells can be
      genetically dissociated. Furthermore, the ability of the E2F-1 DNA-binding domain
      alone to block one manifestation of RB action is consistent with the notion that
      RB-E2F complexes actively repress transcription upon binding to certain E2F
      responsive promoters. In keeping with this view, we show here that coproduction
      of an E2F1 mutant capable of binding to DNA, yet unable to transactivate, is
      sufficient to block RB-mediated transcriptional repression.

PMID- 7823944
TI  - High-frequency gene conversion between repeated C mu sequences integrated at the
      chromosomal immunoglobulin mu locus in mouse hybridoma cells.
AB  - The occurrence of mitotic recombination between repeated immunoglobulin mu gene
      constant (C mu) region sequences stably integrated at the haploid chromosomal
      immunoglobulin mu locus in murine hybridoma cells was investigated. Recombination
      events are detected as changes in hapten-specific immunoglobulin M production.
      Recombination occurs with high frequency (0.5 to 0.8%) by a mechanism consistent
      with gene conversion. A double-strand break repair-like mechanism is suggested by
      the finding that repair of a 2-bp deletion mutation and a 2-bp insertion mutation
      occurs with parity in a donor-directed manner. The results also suggest that the
      gene conversion process is directional in that the 5' C mu region sequence is
      preferentially converted.

PMID- 7823945
TI  - Constitutive c-myb expression in K562 cells inhibits induced erythroid
      differentiation but not tetradecanoyl phorbol acetate-induced megakaryocytic
      differentiation.
AB  - K562 cells were stably transfected with a plasmid vector constitutively
      expressing a full-length human c-myb gene. Parental cells possess the dual
      potential of inducibility of cellular differentiation along two lineages, i.e.,
      erythroid and megakaryocytic. The resulting lineage is dependent on the inducing
      agent, with a number of compounds being competent to various degrees for inducing
      erythroid differentiation, while the tumor promoter tetradecanoyl phorbol acetate
      (TPA) induces a macrophage-like morphology with enhanced expression of proteins
      associated with megakaryocytes. Exogeneous expression of c-myb in transfected
      cell lines abrogated erythroid differentiation induced by cadaverine or cytosine
      arabinoside as assessed by hemoglobin production. However, TPA-induced
      megakaryocytic differentiation was left intact, as assessed by cell morphology,
      cytochemical staining, and the expression of the megakaryocytic antigens. These
      results indicate that c-Myb and protein kinase C play important roles in cellular
      differentiation of K562 cells and suggest that agents which directly modulate
      protein kinase C can induce differentiation in spite of constitutively high
      levels of c-Myb.

PMID- 7823946
TI  - In vivo analysis of sequences required for translation of cytochrome b
      transcripts in yeast mitochondria.
AB  - Respiratory chain proteins encoded by the yeast mitochondrial genome are
      synthesized within the organelle. Mitochondrial mRNAs lack a 5' cap structure and
      contain long AU-rich 5' untranslated regions (UTRs) with many potential
      translational start sites and no apparent Shine-Dalgarno-like complementarity to
      the 15S mitochondrial rRNA. However, translation initiation requires specific
      interactions between the 5' UTRs of the mRNAs, mRNA-specific activators, and the
      ribosomes. In an initial step toward identifying potential binding sites for the
      mRNA-specific translational activators and the ribosomes, we have analyzed the
      effects of deletions in the 5' UTR of the mitochondrial COB gene on translation
      of COB transcripts in vivo. The deletions define two regions of the COB 5' UTR
      that are important for translation and indicate that sequence just 5' of the AUG
      is involved in selection of the correct start codon. Taken together, the data
      implicate specific regions of the 5' UTR of COB mRNA as possible targets for the
      mitochondrial translational machinery.

PMID- 7823947
TI  - The nonconserved hinge region and distinct amino-terminal domains of the ROR
      alpha orphan nuclear receptor isoforms are required for proper DNA bending and
      ROR alpha-DNA interactions.
AB  - ROR alpha 1 and ROR alpha 2 are two isoforms of a novel member of the steroid
      thyroid-retinoid receptor superfamily and are considered orphan receptors since
      their cognate ligand has yet to be identified. These putative receptors have
      previously been shown to bind as monomers to a DNA recognition sequence composed
      of two distinct moieties, a 3' nuclear receptor core half-site AGGTCA preceded by
      a 5' AT-rich sequence. Recognition of this bipartite hormone response element
      (RORE) requires both the zinc-binding motifs and a group of amino acid residues
      located at the carboxy-terminal end of the DNA-binding domain (DBD) which is
      referred to here as the carboxy-terminal extension. In this report, we show that
      binding of ROR alpha 1 and ROR alpha 2 to the RORE induces a large DNA bend of
      approximately 130 degrees which may be important for receptor function. The
      overall direction of the DNA bend is towards the major groove at the center of
      the 3' AGGTCA half-site. The presence of the nonconserved hinge region which is
      located between the DBD and the putative ligand-binding domain (LBD) or ROR alpha
      is required for maximal DNA bending. Deletion of a large portion of the amino
      terminal domain (NTD) of the ROR alpha protein does not alter the DNA bend angle
      but shifts the DNA bend center 5' relative to the bend induced by intact ROR
      alpha. Methylation interference studies using the NTD-deleted ROR alpha 1 mutant
      indicate that some DNA contacts in the 5' AT-rich half of the RORE are also
      shifted 5', while those in the 3' AGGTCA half-site are unaffected. These results
      are consistent with a model in which the ROR alpha NTD and the nonconserved hinge
      region orient the zinc-binding motifs and the carboxy-terminal extension of the
      ROR alpha DBD relative to each other to achieve proper interactions with the two
      halves of its recognition site. Transactivation studies suggest that both protein
      induced DNA bending and protein-protein interactions are important for receptor
      function.

PMID- 7823948
TI  - Characterization of cis-acting sequences and decay intermediates involved in
      nonsense-mediated mRNA turnover.
AB  - Several lines of evidence indicate that the processes of mRNA turnover and
      translation are intimately linked and that understanding this relationship is
      critical to elucidating the mechanism of mRNA decay. One clear example of this
      relationship is the observation that nonsense mutations can accelerate the decay
      of mRNAs in a process that we term nonsense-mediated mRNA decay. The experiments
      described here demonstrate that in the yeast Saccharomyces cerevisiae premature
      translational termination within the initial two-thirds of the PGK1 coding region
      accelerates decay of that transcript regardless of which of the stop codons is
      used. Nonsense mutations within the last quarter of the coding region have no
      effect on PGK1 mRNA decay. The sequences required for nonsense-mediated mRNA
      decay include a termination codon and specific sequences 3' to the nonsense
      mutation. Translation of two-thirds of the PGK1 coding region inactivates the
      nonsense-mediated mRNA decay pathway. This observation explains why carboxyl
      terminal nonsense mutations are resistant to accelerated decay. Characterization
      of the decay of nonsense-containing HIS4 transcripts yielded results mirroring
      those described above, suggesting that the sequence requirements described for
      the PGK1 transcript are likely to be a general characteristic of this decay
      pathway. In addition, an analysis of the decay intermediates of nonsense
      containing mRNAs indicates that nonsense-mediated mRNA decay flows through a
      pathway similar to that described for a class of wild-type transcripts. The
      initial cleavage event occurs near the 5' terminus of the nonsense-containing
      transcript and is followed by 5'-->3' exonucleolytic digestion. A model for
      nonsense-mediated mRNA decay based on these results is discussed.

PMID- 7823949
TI  - CalpA, a Drosophila calpain homolog specifically expressed in a small set of
      nerve, midgut, and blood cells.
AB  - Calpains are calcium-dependent proteases believed to participate in calcium
      regulated signal pathways in cells. Ubiquitous calpains as well as tissue
      specific calpains have been found in vertebrates. We isolated cDNA clones for a
      highly tissue-specific calpain gene from Drosophila melanogaster, CalpA, at 56C-D
      on the second chromosome. The expression of the CalpA gene product was monitored
      by using a specific antiserum directed against the product expressed by one cDNA
      clone. The encoded protein is found in a few neurons in the central nervous
      system, in scattered endocrine cells in the midgut, and in blood cells. In the
      blood cell line mbn-2, calpain is associated with a granular component in the
      cytoplasm. The expression of this protein is more restricted than that of the
      corresponding transcripts, which are widely distributed in the central nervous
      system, digestive tract, and other tissues. The sequence of CalpA is closely
      related to that of vertebrate calpains, but an additional segment is inserted in
      the calmodulin-like carboxy-terminal domain. This insert contains a hydrophobic
      region that may be involved in membrane attachment of the enzyme. Differential
      splicing also gives rise to a minor transcript that lacks the calmodulin-like
      domain.

PMID- 7823950
TI  - Targeted disruption of retinoic acid receptor alpha (RAR alpha) and RAR gamma
      results in receptor-specific alterations in retinoic acid-mediated
      differentiation and retinoic acid metabolism.
AB  - F9 embryonic teratocarcinoma stem cells differentiate into an epithelial cell
      type called extraembryonic endoderm when treated with retinoic acid (RA), a
      derivative of retinol (vitamin A). This differentiation is presumably mediated
      through the actions of retinoid receptors, the RARs and RXRs. To delineate the
      functions of each of the different retinoid receptors in this model system, we
      have generated F9 cell lines in which both copies of either the RAR alpha gene or
      the RAR gamma gene are disrupted by homologous recombination. The absence of RAR
      alpha is associated with a reduction in the RA-induced expression of both the
      CRABP-II and Hoxb-1 (formerly 2.9) genes. The absence of RAR gamma is associated
      with a loss of the RA-inducible expression of the Hoxa-1 (formerly Hox-1.6), Hoxa
      3 (formerly Hox-1.5), laminin B1, collagen IV (alpha 1), GATA-4, and BMP-2 genes.
      Furthermore, the loss of RAR gamma is associated with a reduction in the
      metabolism of all-trans-RA to more polar derivatives, while the loss of RAR alpha
      is associated with an increase in metabolism of RA relative to wild-type F9
      cells. Thus, each of these RARs exhibits some specificity with respect to the
      regulation of differentiation-specific gene expression. These results provide an
      explanation for the expression of multiple RAR types within one cell type and
      suggest that each RAR has specific functions.

PMID- 7823951
TI  - The erythroid Kruppel-like factor transactivation domain is a critical component
      for cell-specific inducibility of a beta-globin promoter.
AB  - Erythroid Kruppel-like factor (EKLF) is an erythroid cell-specific DNA-binding
      protein that activates transcription from the beta-globin CACCC element, a
      functionally important and evolutionarily conserved component of globin as well
      as other erythroid cell-specific promoters and enhancers. We have attempted to
      elucidate the molecular role of EKLF in erythrocyte-specific transcriptional
      activation. First, in vivo and in vitro analyses have been used to demonstrate
      that the level of activation by EKLF is dependent on the orientation and number
      of CACCC elements, that EKLF contains separable activation and DNA-binding
      domains, and that the EKLF proline-rich region is a potent activator in CV-1
      cells when fused to a nonrelated DNA-binding module. Second, we have established
      a transient assay in murine erythroleukemia cells in which reproducible levels of
      a reporter can be induced when linked to a locus control region enhancer-beta
      globin promoter and in which induction is abolished when the promoter CAC site is
      mutated to a GAL site. Third, we demonstrate that the EKLF transactivation
      region, when fused to the GAL DNA-binding domain, can restore inducibility to
      this mutated construct and that this inducibility exhibits activator-, promoter-,
      and cell-type specificity. These results demonstrate that EKLF provides a crucial
      transactivation function for globin expression and further reinforce the idea
      that EKLF is an important regulator of CACCC element-directed transcription in
      erythroid cells.

PMID- 7823952
TI  - Transcriptional repression by Msx-1 does not require homeodomain DNA-binding
      sites.
AB  - This study investigates the transcriptional properties of Msx-1, a murine
      homeodomain protein which has been proposed to play a key role in regulating the
      differentiation and/or proliferation state of specific cell populations during
      embryogenesis. We show, using basal and activated transcription templates, that
      Msx-1 is a potent repressor of transcription and can function through both TATA
      containing and TATA-less promoters. Moreover, repression in vivo and in vitro
      occurs in the absence of DNA-binding sites for the Msx-1 homeodomain. Utilizing a
      series of truncated Msx-1 polypeptides, we show that multiple regions of Msx-1
      contribute to repression, and these are rich in alanine, glycine, and proline
      residues. When fused to a heterologous DNA-binding domain, both N- and C-terminal
      regions of Msx-1 retain repressor function, which is dependent upon the presence
      of the heterologous DNA-binding site. Moreover, a polypeptide consisting of the
      full-length Msx-1 fused to a heterologous DNA-binding domain is a more potent
      repressor than either the N- or C-terminal regions alone, and this fusion retains
      the ability to repress transcription in the absence of the heterologous DNA site.
      We further show that Msx-1 represses transcription in vitro in a purified
      reconstituted assay system and interacts with protein complexes composed of TBP
      and TFIIA (DA) and TBP, TFIIA, and TFIIB (DAB) in gel retardation assays,
      suggesting that the mechanism of repression is mediated through interaction(s)
      with a component(s) of the core transcription complex. We speculate that the
      repressor function of Msx-1 is critical for its proposed role in embryogenesis as
      a regulator of cellular differentiation.

PMID- 7823953
TI  - The PEST-like sequence of I kappa B alpha is responsible for inhibition of DNA
      binding but not for cytoplasmic retention of c-Rel or RelA homodimers.
AB  - In most cells, proteins belonging to the Rel/NF-kappa B family of transcription
      factors are held in inactive form in the cytoplasm by an inhibitor protein, I
      kappa B alpha. Stimulation of the cells leads to degradation of the inhibitor and
      transit of active DNA-binding Rel/NF-kappa B dimers to the nucleus. I kappa B
      alpha is also able to inhibit DNA binding by Rel/NF-kappa B dimers in vitro,
      suggesting that it may perform the same function in cells when the activating
      signal is no longer present. Structurally, the human I kappa B alpha molecule can
      be divided into three sections: a 70-amino-acid N terminus with no known
      function, a 205-residue midsection composed of six ankyrin-like repeats, and a
      very acidic 42-amino-acid C terminus that resembles a PEST sequence. In this
      study we examined how the structural elements of the I kappa B alpha protein
      correlate with its functional capabilities both in vitro and in vivo. Using a
      battery of I kappa B alpha mutants, we show that (i) a dimer binds a single I
      kappa B alpha molecule, (ii) the acidic C-terminal region of I kappa B alpha is
      not required for protein-protein binding and does not mask the nuclear
      localization signal of the dimer, (iii) the same C-terminal region is required
      for inhibition of DNA binding, and (iv) this inhibition may be accomplished by
      direct interaction between the PEST-like region and the DNA-binding region of one
      of the subunits of the dimer.

PMID- 7823954
TI  - Cell cycle-dependent phosphorylation and dephosphorylation of the yeast DNA
      polymerase alpha-primase B subunit.
AB  - The yeast DNA polymerase alpha-primase B subunit functions in initiation of DNA
      replication. This protein is present in two forms, of 86 and 91 kDa, and the p91
      polypeptide results from cell cycle-regulated phosphorylation of p86. The B
      subunit present in G1 arises by dephosphorylation of p91 while cells are exiting
      from mitosis, becomes phosphorylated in early S phase, and is competent and
      sufficient to initiate DNA replication. The B subunit transiently synthesized as
      a consequence of periodic transcription of the POL12 gene is phosphorylated no
      earlier than G2. Phosphorylation of the B subunit does not require execution of
      the CDC7-dependent step and ongoing DNA synthesis. We suggest that
      posttranslational modifications of the B subunit might modulate the role of DNA
      polymerase alpha-primase in DNA replication.

PMID- 7823955
TI  - Multiple response elements in the Sex-lethal early promoter ensure its female
      specific expression pattern.
AB  - The choice of sexual identity in somatic tissues of the fruit fly Drosophila
      melanogaster is determined early in embryogenesis by the X-chromosome-to-autosome
      (X/A) ratio. The system that signals the X/A ratio selects the sexual development
      pathway by determining the activity state of the binary switch Sex-lethal (Sxl).
      In 2X/2A animals, the X/A signalling system turns the Sxl gene on, ultimately
      activating an RNA-splicing autoregulatory feedback loop which serves to maintain
      the female state during the remainder of development. In 1X/2A animals, this
      autoregulatory feedback loop is not activated and the male state is subsequently
      maintained by the default splicing machinery. In the studies reported here, we
      have examined how the X/A signalling system controls the initial choice of sexual
      identity through its action on a special early embryonic Sxl promoter, Sxl-Pe. We
      show that in the early embryo, the activity of Sxl-Pe is controlled in a highly
      dose-sensitive fashion by the genes on the X chromosome that function as
      numerator elements and by genes located on the autosomes that function as
      denominator elements. Functional dissection of Sxl-Pe indicates that activating
      the promoter in females requires the cumulative action of multiple numerator
      genes which appear to exert their effects through reiterated cis-acting target
      sites in the promoter. Conversely, maintaining the promoter silent in males
      requires the repressive activities of denominator genes, and at least one of the
      denominator genes also appears to function through target sequences within the
      promoter.

PMID- 7823956
TI  - A deficiency of the small GTPase rab8 inhibits membrane traffic in developing
      neurons.
AB  - One of the major activities of developing neurons is the transport of new
      membrane to the growing axon. Candidates for playing a key role in the regulation
      of this intense traffic are the small GTP-binding proteins of the rab family. We
      have used hippocampal neurons in culture and analyzed membrane traffic activity
      after suppressing the expression of the small GTP-binding protein rab8.
      Inhibition of protein expression was accomplished by using sequence-specific
      antisense oligonucleotides. While rab8 depletion resulted in the blockage of
      morphological maturation in 95% of the neurons, suppression of expression of
      another rab protein, rab3a, had no effect, and all neurons developed normal axons
      and dendrites. The impairment of neuronal maturation by rab8 antisense treatment
      was due to inhibition of membrane traffic. Thus, by using video-enhanced
      differential interference contrast microscopy, we observed in the rab8-depleted
      cells a dramatic reduction in the number of vesicles undergoing anterograde
      transport. Moreover, by incubating antisense-treated neurons with Bodipy-labeled
      ceramide, a fluorescent marker for newly formed exocytic vesicles, we observed
      fluorescence labeling restricted to the Golgi apparatus, whereas in control cells
      labeling was found also in the neurites. These results show the role of the small
      GTPase rab8 in membrane traffic during neuronal process outgrowth.

PMID- 7823957
TI  - ets-1 in astrocytes: expression and transmitter-evoked phosphorylation.
AB  - The ets-1 protein has been primarily studied as a sequence-specific
      transcriptional regulator that is predominately expressed in lymphoid cells. In
      this report, we show that ets-1 is also expressed in astrocytes and astrocytoma
      cells and is regulated during both signal transduction and differentiation. Both
      isoforms of ets-1, p51 and p42, were found in astrocytes and astrocytoma cells,
      but whereas expression of p51 was strong, p42, the alternate splice product
      previously shown to lack the phosphorylation domain, was difficult to detect and
      was present at a level 10- to 40-fold lower than that of p51. This differed by
      roughly an order of magnitude from the ratio generally observable in T cells and
      thymocytes. In two astrocytoma lines of human origin, CCF and 1321N1, ets-1
      phosphorylation was stimulated by bradykinin and carbachol, respectively.
      Glutamate, norepinephrine, and bradykinin elicited phosphorylation of p51 in
      cultures of primary rat type 1 astrocytes. ets-1 phosphorylation was dramatically
      blocked by KT5926, an inhibitor of myosin light-chain kinase, suggesting that
      this kinase may be involved in phosphorylation of ets-1 in vivo. Investigations
      of retinoic acid-induced differentiation in P19 cells provided further support
      for a strong correlation of ets-1 with the pathway for astrocyte differentiation.

PMID- 7823958
TI  - Activation-induced T-cell death is cell cycle dependent and regulated by cyclin
      B.
AB  - Developing thymocytes and some T-cell hybridomas undergo activation-dependent
      programmed cell death. Although recent studies have identified some critical
      regulators in programmed cell death, the role of cell cycle regulation in
      activation-induced cell death in T cells has not been addressed. We demonstrate
      that synchronized T-cell hybridomas, irrespective of the point in the cell cycle
      at which they are activated, stop cycling shortly after they reach G2/M. These
      cells exhibit the diagnostic characteristics of apoptotic cell death. Although
      p34cdc2 levels are not perturbed after activation of synchronously cycling T
      cells, cyclin B- and p34cdc2-associated histone H1 kinase activity is
      persistently elevated. This activation-dependent induction of H1 kinase activity
      in T cells is associated with a decrease in the phosphotyrosine content of
      p34cdc2. We also demonstrate that transient inappropriate coexpression of cyclin
      B with p34cdc2 induces DNA fragmentation in a heterologous cell type. Finally, in
      T cells, cyclin B-specific antisense oligonucleotides suppress activation-induced
      cell death but not cell death induced by exposure to dexamethasone. We therefore
      conclude that a persistent elevation of the level of cyclin B kinase is required
      for activation-induced programmed T-cell death.

PMID- 7823959
TI  - Characterization of mechanisms involved in transrepression of NF-kappa B by
      activated glucocorticoid receptors.
AB  - Glucocorticoids are potent immunosuppressants which work in part by inhibiting
      cytokine gene transcription. We show here that NF-kappa B, an important regulator
      of numerous cytokine genes, is functionally inhibited by the synthetic
      glucocorticoid dexamethasone (DEX). In transfection experiments, DEX treatment in
      the presence of cotransfected glucocorticoid receptor (GR) inhibits NF-kappa B
      p65-mediated gene expression and p65 inhibits GR activation of a glucocorticoid
      response element. Evidence is presented for a direct interaction between GR and
      the NF-kappa B subunits p65 and p50. In addition, we demonstrate that the ability
      of p65, p50, and c-rel subunits to bind DNA is inhibited by DEX and GR. In HeLa
      cells, DEX activation of endogenous GR is sufficient to block tumor necrosis
      factor alpha or interleukin 1 activation of NF-kappa B at the levels of both DNA
      binding and transcriptional activation. DEX treatment of HeLa cells also results
      in a significant loss of nuclear p65 and a slight increase in cytoplasmic p65.
      These data reveal a second mechanism by which NF-kappa B activity may be
      regulated by DEX. We also report that RU486 treatment of wild-type GR and DEX
      treatment of a transactivation mutant of GR each can significantly inhibit p65
      activity. In addition, we found that the zinc finger domain of GR is necessary
      for the inhibition of p65. This domain is also required for GR repression of AP
      1. Surprisingly, while both AP-1 and NF-kappa B can be inhibited by activated GR,
      synergistic NF-kappa B/AP-1 activity is largely unaffected. These data suggest
      that NF-kappa B, AP-1, and GR interact in a complex regulatory network to
      modulate gene expression and that cross-coupling of NF-kappa B and GR plays an
      important role in glucocorticoid-mediated repression of cytokine transcription.

PMID- 7823960
TI  - Efficient selection and characterization of mutants of a human cell line which
      are defective in mitochondrial DNA-encoded subunits of respiratory NADH
      dehydrogenase.
AB  - The mitochondrial NADH dehydrogenase (complex I) in mammalian cells is a
      multimeric enzyme consisting of approximately 40 subunits, 7 of which are encoded
      in mitochondrial DNA (mtDNA). Very little is known about the function of these
      mtDNA-encoded subunits. In this paper, we describe the efficient isolation from a
      human cell line of mutants affected in any of these subunits. In the course of
      analysis of eight mutants of the human cell line VA2B selected for their
      resistance to high concentrations of the complex I inhibitor rotenone, seven were
      found to be respiration deficient, and among these, six exhibited a specific
      defect of complex I. Transfer of mitochondria from these six mutants into human
      mtDNA-less cells revealed, surprisingly, in all cases a cotransfer of the complex
      I defect but not of the rotenone resistance. This result indicated that the
      rotenone resistance resulted from a nuclear mutation, while the respiration
      defect was produced by an mtDNA mutation. A detailed molecular analysis of the
      six complex I-deficient mutants revealed that two of them exhibited a frameshift
      mutation in the ND4 gene, in homoplasmic or in heteroplasmic form, resulting in
      the complete or partial loss, respectively, of the ND4 subunit; two other mutants
      exhibited a frameshift mutation in the ND5 gene, in near-homoplasmic or
      heteroplasmic form, resulting in the ND5 subunit being undetectable or strongly
      decreased, respectively. It was previously reported (G. Hofhaus and G. Attardi,
      EMBO J. 12:3043-3048, 1993) that the mutant completely lacking the ND4 subunit
      exhibited a total loss of NADH:Q1 oxidoreductase activity and a lack of assembly
      of the mtDNA-encoded subunits of complex I. By contrast, in the mutant
      characterized in this study in which the ND5 subunit was not detectable and which
      was nearly totally deficient in complex I activity, the capacity to assemble the
      mtDNA-encoded subunits of the enzyme was preserved, although with a decreased
      efficiency or a reduced stability of the assembled complex. The two remaining
      complex I-deficient mutants exhibited a normal rate of synthesis and assembly of
      the mtDNA-encoded subunits of the enzyme, and the mtDNA mutation(s) responsible
      for their NADH dehydrogenase defect remains to be identified. The selection
      scheme used in this work has proven to be very valuable for the isolation of
      mutants from the VA2B cell line which are affected in different mtDNA-encoded
      subunits of complex I and may be applicable to other cell lines.

PMID- 7823961
TI  - Interferon regulatory factor 1 is required for mouse Gbp gene activation by gamma
      interferon.
AB  - Full-scale transcriptional activation of the mouse Gbp genes by gamma interferon
      (IFN-gamma) requires protein synthesis in embryonic fibroblasts. Although the Gbp
      1 and Gbp-2 promoters contain binding sites for transcription factors Stat1 and
      IFN regulatory factor 1 (IRF-1), deletion analysis revealed that the Stat1
      binding site is dispensable for IFN-gamma inducibility of Gbp promoter constructs
      in transfected fibroblasts. However, activation of the mouse Gbp promoter by IFN
      gamma requires transcription factor IRF-1. Transient overexpression of IRF-1 cDNA
      in mouse fibroblasts resulted in high-level expression of Gbp promoter
      constructs. Unlike wild-type cells, IRF-1% embryonic stem cells lacking
      functional transcription factor IRF-1 contained very low levels of Gbp
      transcripts that were not increased in response to differentiation or treatment
      with IFN-gamma. Treatment of IRF-1% mice with IFN-gamma resulted in barely
      detectable levels of Gbp RNA in spleens, lungs, and livers, whereas such
      treatment induced high levels of Gbp RNA in the organs of wild-type mice. These
      observations suggest two alternative pathways for transcriptional induction of
      genes in response to IFN-gamma: immediate response that results from activation
      of preformed Stat1 and delayed response that results from induced de novo
      synthesis of transcription factor IRF-1.

PMID- 7823962
TI  - The glutamine-rich activation domains of human Sp1 do not stimulate transcription
      in Saccharomyces cerevisiae.
AB  - Eukaryotic transcriptional activators have been classified on the basis of the
      characteristics of their activation domains. Acidic activation domains, such as
      those in the yeast GAL4 or GNC4 proteins and the herpes simplex virus activator
      VP16, stimulate RNA polymerase II transcription when introduced into a variety of
      eukaryotic cells. This species interchangeability demonstrates that the mechanism
      by which acidic activation domains function is highly conserved in the eukaryotic
      kingdom. To determine whether such a conservation of function exists for a
      different class of activation domain, we have tested whether the glutamine-rich
      activation domains of the human transcriptional activator Sp1 function in the
      yeast Saccharomyces cerevisiae. We report here that the glutamine-rich domains of
      Sp1 do not stimulate transcription in S. cerevisiae, even when accompanied by
      human TATA-box binding protein (TBP) or human-yeast TATA-box binding protein
      hybrids. Thus, in contrast to the case for acidic activation domains, the
      mechanism by which glutamine-rich domains stimulate transcription is not
      conserved between S. cerevisiae and humans.

PMID- 7823963
TI  - Characterization of a mammalian homolog of the Escherichia coli MutY mismatch
      repair protein.
AB  - A protein homologous to the Escherichia coli MutY protein, referred to as MYH,
      has been identified in nuclear extracts of calf thymus and human HeLa cells.
      Western blot (immunoblot) analysis using polyclonal antibodies to the E. coli
      MutY protein detected a protein of 65 kDa in both extracts. Partial purification
      of MYH from calf thymus cells revealed a 65-kDa protein as well as a functional
      but apparently degraded form of 36 kDa, as determined by glycerol gradient
      centrifugation and immunoblotting with anti-MutY antibodies. Calf MYH is a DNA
      glycosylase that specifically removes mispaired adenines from A/G, A/7,8-dihydro
      8-oxodeoxyguanine (8-oxoG or GO), and A/C mismatches (mismatches indicated by
      slashes). A nicking activity that is either associated with or copurified with
      MYH was also detected. Nicking was observed at the first phosphodiester bond 3'
      to the apurinic or apyrimidinic (AP) site generated by the glycosylase activity.
      The nicking activity on A/C mismatches was 30-fold lower and the activity on A/GO
      mismatches was twofold lower than that on A/G mismatches. No nicking activity was
      detected on substrates containing other selected mismatches or homoduplexes.
      Nicking activity on DNA containing A/G mismatches was inhibited in the presence
      of anti-MutY antibodies or upon treatment with potassium ferricyanide, which
      oxidizes iron-sulfur clusters. Gel shift analysis showed specific binding complex
      formation with A/G and A/GO substrates, but not with A/A, C.GO, and C.G
      substrates. Binding is sevenfold greater on A/GO substrates than on A/G
      substrates. The eukaryotic MYH may be involved in the major repair of both
      replication errors and oxidative damage to DNA, the same functions as those of
      the E. coli MutY protein.

PMID- 7823965
TI  - Efficient MHC class I-peptide binding is required but does not ensure MHC class I
      restricted immunogenicity.
AB  - Cytotoxic T lymphocyte (CTL) epitopes are naturally processed peptides bound and
      presented by major histocompatibility (MHC) class I molecules. Since they are
      expressed at the cell surface in sufficient amounts to be recognized by CTL, it
      is generally believed, and in some cases demonstrated, that they bind efficiently
      to MHC class I molecules in vivo. Based on this knowledge, candidate CTL epitopes
      are now searched for by identifying peptides that efficiently bind to MHC class I
      molecules in vitro. We analysed whether this approach is valid by systematically
      investigating the relationship between MHC class I-peptide binding and peptide
      immunogenicity. Fifteen peptides that represent known CTL epitopes were tested
      for their MHC class I binding ability. In a comparative study with 83 peptides
      that bear the appropriate MHC class I allele-specific motifs but do not contain
      known CTL epitopes, the CTL epitope-bearing peptides showed the highest binding
      affinity for MHC class I. This was true for two MHC class I alleles in two
      different assay systems that monitor peptide-MHC class I binding. Furthermore,
      selected motif-bearing Kb binding peptides were used to induce peptide-specific
      CTL responses in mice. Only a subset of the high affinity Kb binding peptides
      induced reproducible peptide-specific CTL responses, whereas none of the low
      affinity Kb binding peptides induced a response. Taken together, these results
      indicate that efficient peptide-MHC class I binding is required for
      immunogenicity. Vice versa, immunogenicity is not guaranteed by efficient peptide
      MHC class I binding, implying that additional factors are involved. Nevertheless,
      selection of candidate CTL epitopes on the basis of MHC class I binding seems
      valid. Our data indicate that, although an excess of peptides might be selected,
      the chance of missing immunogenic peptides is minimal.

PMID- 7823964
TI  - Functional domains of Pho81p, an inhibitor of Pho85p protein kinase, in the
      transduction pathway of Pi signals in Saccharomyces cerevisiae.
AB  - The PHO81 gene is thought to encode an inhibitor of the negative regulators
      (Pho80p and Pho85p) in the phosphatase (PHO) regulon. Transcription of PHO81 is
      regulated by Pi signals through the same PHO regulatory system. Elimination of
      the PHO81 promoter or its substitution by the GAL1 promoter revealed that
      stimulation of the PHO regulatory system requires both increased transcription of
      PHO81 and a Pi starvation signal. The predicted Pho81p protein contains 1,179
      amino acids (aa) and has six repeats of an ankyrin-like sequence in its central
      region. The minimum amino acid sequence required for Pho81p function was narrowed
      down to a 141-aa segment (aa 584 to 724), which contains the fifth and sixth
      repeats of the ankyrin-like motif. The third to sixth repeats of the ankyrin-like
      motif of Pho81p have significant similarities to that of p16INK4, which inhibits
      activity of the human cyclin D-CDK4 kinase complex. Deletion analyses revealed
      that the N- and C-terminal regions of Pho81p behave as negative and positive
      regulatory domains, respectively, for the minimal 141-aa region. The negative
      regulatory activity of the N-terminal domain was antagonized by a C-terminal
      segment of Pho81p supplied in trans. All four known classes of PHO81c mutations
      that show repressible acid phosphatase activity in high-Pi medium affect the N
      terminal half of Pho81p. An in vitro assay showed that a glutathione S
      transferase-Pho81p fusion protein inhibits the Pho85p protein kinase. Association
      of Pho81p with Pho85p or with the Pho80p-Pho85p complex was demonstrated by the
      two-hybrid system.

PMID- 7823966
TI  - T cell recognition of the posttranslationally cleaved intersubunit region of
      influenza virus hemagglutinin.
AB  - The influenza virus hemagglutinin is synthesized as a single polypeptide chain,
      but upon maturation it will posttranslationally be modified by a host cell
      related trypsin-like enzyme. The enzymatic cleavage attacks the so-called
      intersubunit region of the molecule giving rise to covalently linked HA1 and HA2
      subunits. An I-Ed-restricted T cell epitope was identified in the highly
      conserved intact intersubunit region of the influenza virus hemagglutinin. T cell
      recognition of a 25-mer synthetic peptide comprising the intact intersubunit
      region does not require further processing and the elimination of the intervening
      Arg residue coupling the fusion peptide to the C-terminal segment of HA1 does not
      abolish the T cell activating capacity. The fine specificity pattern of a T cell
      hybridoma similar to that of the polyclonal T cell response demonstrates that a
      single T cell receptor is able to recognize peptides of different sizes
      representing not only the uncleaved but also the cleaved form of this
      hemagglutinin region. Based on specificity studies the epitope was localized to
      the C-terminal 11 amino acids of the HA1 subunit. The cross-reactivity of peptide
      primed T cells with influenza virus infected antigen-presenting cells shows that
      fragments comprising the identified epitope of the intersubunit region can be
      generated as a result of natural processing of the hemagglutinin molecule. As
      antigen-presenting cells are lacking the enzyme which is responsible for the
      posttranslational modification of newly synthesized hemagglutinin molecules, the
      role of immature viral proteins in immune recognition is discussed.

PMID- 7823967
TI  - Carbohydrate heterogeneity of human myeloma proteins of the IgA1 and IgA2
      subclasses.
AB  - Comparative studies of the N-linked carbohydrate chains of human myeloma proteins
      of the IgA1 and IgA2 subclasses were performed. The N-linked carbohydrate chains
      were released by hydrazinolysis from the polypeptide backbone, converted to
      radioactive oligosaccharides by sodium borotritide reduction after N-acetylation
      and separated into one neutral and two acidic fractions by paper electrophoresis.
      The acidic oligosaccharides were completely converted to neutral oligosaccharides
      by sialidase treatment, indicating that they were sialyl derivatives. The neutral
      and sialidase-treated acidic oligosaccharides were further fractionated by Bio
      Gel P-4 column chromatography. Structural studies of each oligosaccharide by
      sequential exoglycosidase digestion and methylation analysis revealed that human
      myeloma IgA proteins contained significant amounts of biantennary complex-type
      carbohydrate chains in addition to a small amount of the high mannose-type. The
      results indicated that the oligosaccharide structures of human IgA1 and IgA2
      display a high degree of heterogeneity not only in the number of carbohydrate
      chains, but also in their composition.

PMID- 7823968
TI  - Identification of potential CTL epitopes of tumor-associated antigen MAGE-1 for
      five common HLA-A alleles.
AB  - Identification of CTL epitopes for tumor-specific responses is important for the
      development of immunotherapies to treat cancer patients. We have developed a
      strategy to identify potential CTL epitopes based on screening of sequences of
      target proteins for presence of specific motifs recognized by the most common HLA
      A alleles, and identification of high affinity binding peptides using in vitro
      quantitative assays. A systematic analysis using the sequence of the product of
      the tumor-associated MAGE-1 gene has been carried out. All possible peptides of
      nine and ten residues, containing binding motifs for HLA-A1, -A2.1, A-3.2, -A11
      and -A24 were synthesized and tested for binding using a quantitative assay. Out
      of 237 possible peptide/MHC combinations, 47 cases demonstrated good binding
      affinity (Kd < or = 500 nM). Several peptides were identified as good MHC binders
      for each one of the five HLA-A alleles studied (five for HLA-A1, 11 for HLA-A2.1,
      10 for HLA-A3.2, 16 for HLA-A11 and five for HLA-A24. Furthermore, eight of these
      peptides were found to bind well to more than one HLA-A allele. These results
      have important implications for the development of immunotherapeutic vaccines to
      treat malignant melanoma.

PMID- 7823969
TI  - Peptide sequences binding to MHC class I proteins.
AB  - Motifs for peptides which bind specifically to the human class I major
      histocompatibility complex molecules HLA-A2 and B7 were determined by sequence
      analysis of class I-bound peptides selected from a random synthetic library of
      nonamers. Thirteen individual peptides were sequenced for HLA-A2, twelve
      individual and nine pooled peptides were sequenced for HLA-B7. Analysis of
      sequence alignment implicated four peptide positions in potential contact with
      the class I HLA-A2 molecule and three positions for the HLA-B7 molecule. The
      results demonstrate that a synthetic peptide library can be used to identify
      allele-specific motifs for class I molecules, providing information comparable to
      the results obtained from sequencing endogenous peptides. This method utilizes
      denatured class I heavy chains, and similar results were obtained using a class I
      protein purified from mammalian cells or by expression in Escherichia coli. This
      method has the potential to detect peptides which may not be generated
      physiologically, but due to their binding properties, may be valuable to predict
      or engineer immunomodulatory T cell epitopes.

PMID- 7823970
TI  - Binding of bivalent ligand to cell surface IgE: can one detect ring formation?
AB  - It is well established that aggregation of cell surface immunoglobulin is
      involved in signal transduction by cells of the immune system. It is less well
      understood what special properties of these cell surface aggregates are important
      in initiating the signal cascade. Several authors have proposed that cells
      respond to the size (Fewtrell and Metzger (1980) J. Immun. 125, 701-710) as well
      as the stereochemistry (Ortega et al. (1989) Eur. J. Immun. 19, 2251-2256) of
      receptor aggregates. One approach to arriving at data relevant to this question
      has been to construct simple bivalent ligands that can bind to surface
      immunoglobulin. Several authors have suggested that when these bivalent ligands
      interact with surface immunoglobulin the formation of small stable cyclic
      complexes is highly favored. In this paper we consider whether it is possible to
      completely determine the parameters that describe the binding of a bivalent
      ligand to a bivalent receptor with the available experimental technology. We show
      that with the appropriate analysis procedure, using a modified equivalent site
      model, these parameters can be reliably determined from only three experiments
      even when there is a large amount of ring formation.

PMID- 7823971
TI  - Sequence analyses of the native form of a major house dust mite allergen and its
      nascent polypeptide.

PMID- 7823972
TI  - Immunopathogenesis and treatment of the Guillain-Barre syndrome--Part I.
AB  - The etiology of the Guillain-Barre syndrome (GBS) still remains elusive. Recent
      years have witnessed important advances in the delineation of the mechanisms that
      may operate to produce nerve damage. Evidence gathered from cell biology,
      immunology, and immunopathology studies in patients with GBS and animals with
      experimental autoimmune neuritis (EAN) indicate that GBS results from aberrant
      immune responses against components of peripheral nerve. Autoreactive T
      lymphocytes specific for the myelin antigens P0 and P2 and circulating antibodies
      to these antigens and various glycoproteins and glycolipids have been identified
      but their pathogenic role remains unclear. The multiplicity of these factors and
      the involvement of several antigen nonspecific proinflammatory mechanisms suggest
      that a complex interaction of immune pathways results in nerve damage. Data on
      disturbed humoral immunity with particular emphasis on glycolipid antibodies and
      on activation of autoreactive T lymphocytes and macrophages will be reviewed.
      Possible mechanisms underlying initiation of peripheral nerve-directed immune
      responses will be discussed with particular emphasis on the recently highlighted
      association with Campylobacter jejuni infection.

PMID- 7823973
TI  - Immunopathogenesis and treatment of the Guillain-Barre syndrome--Part II.
AB  - In the second part of our review the role of antecedent infections in the
      pathogenesis of GBS is discussed. The association with Campylobacter jejuni (C.
      jejuni) is highlighted and the concept of molecular mimicry, i.e., sharing of
      epitopes between microbes and peripheral nerve, explained. Alternative mechanisms
      to relate an infection with the immune-mediated neuropathy are elaborated.
      Current therapies of the GBS include plasma exchange, high-dose intravenous
      immunoglobulins, and supportive treatment directed to secondary complications.
      Published therapeutic trials are reviewed and future approaches are outlined.
      Principles of general care are also summarized.

PMID- 7823974
TI  - Computational methods for improving estimates of motor unit twitch contraction
      properties.
AB  - Estimates of mechanical properties of human motor units have usually been made
      indirectly, using the technique of "spike-triggered averaging" (STA). In this
      method, a single motor unit action potential is used to synchronize the
      accumulation of an ensemble average of correlated force transients. However,
      under most realizable conditions, these transients are recorded during periods of
      sustained motor unit discharge, in which each motor unit is producing a partially
      fused tetanus. Therefore, the STA technique extracts the characteristics of the
      unfused force transient, instead of the desired single motor unit twitch.
      Although the STA method has been widely used, there is as yet no well-established
      relation between the force transient in the unfused tetanus, and the twitch
      contraction properties of the motor unit. To evaluate the accuracy of the STA as
      a measure of the motor unit mechanical properties, we applied two types of muscle
      models to the force transients recorded in an unfused tetanus, using data derived
      from experiments in which the response to a single twitch was also recorded. Our
      objective was to see whether accurate predictions of single motor unit mechanical
      characteristics are possible, working backward from the STA. The models chosen
      for this task were a linear second order model, and the distribution-moment (DM)
      model. These model predictions were then compared with the STA response, and with
      the twitch properties of the individual motor units. We also evaluated the
      utility of extrapolating the initial slope of the STA backward to improve the
      accuracy of the mechanical estimates. The results of our simulation suggest that
      there is no straightforward relation between the characteristics of the unfused
      tetanus and the mechanical properties of the single twitch. Although our attempts
      to predict the properties of the single twitch from the STA were only partly
      successful, the results of the simulations were far more accurate than those
      derived from the STA alone. Because the errors in the use of the STA method were
      so substantial, we would urge that the STA technique be used with great caution
      as a measure of twitch contraction properties, unless accompanied by appropriate
      simulations of muscle mechanical behavior.

PMID- 7823975
TI  - Nerve conduction changes and fine structural alterations of extra- and intrafusal
      muscle and nerve fibers in streptozotocin diabetic rats.
AB  - Streptozotocin-induced diabetes mellitus is known to cause a reduction of both
      conduction velocity and axon caliber in sciatic nerves and also a decrease in
      muscle fiber size. The present study investigates whether the distal parts of the
      peripheral nervous system, including extra- and intrafusal muscle fibers, are
      more severely affected than the proximal segments in the diabetic state. Proximal
      and distal sensory nerve conduction velocities were monitored during a period of
      3 months in rats rendered diabetic by injection of streptozotocin. Segments of
      the sciatic and ventral coccygeal nerves, and of the biceps femoris and lumbrical
      muscles, were studied by light and electron microscopy, including morphometric
      analysis. In contrast to previous studies, daily suboptimal insulin injections
      were given to prevent acute metabolic complications. Sensory conduction velocity
      in the ventral coccygeal nerve was significantly (P < 0.05) decreased in the
      diabetic rats compared to controls. Proximal and distal nerve segments were
      equally affected. Mean cross-sectional axon area of the sciatic nerve was
      moderately, but significantly (P < 0.05), smaller in insulin-treated diabetic
      rats than in controls. In both the sciatic nerve and the terminal, intrafusal
      nerve segments, occasional axons showed moderate dystrophic changes. Fibers of
      the intrafusal nerve segments appeared to be equally affected compared to the
      fibers in the sciatic nerve, although no quantitative comparison was made. The
      increase of small caliber skeletal muscle fibers in experimental streptozotocin
      induced diabetes was confirmed. These findings indicate that proximal and distal
      segments of peripheral nerves are affected equally in the early stages of
      experimental diabetic neuropathy.

PMID- 7823976
TI  - Sympathetic skin response (SSR) is abnormal in multiple sclerosis.
AB  - As the function of the autonomic nervous system is often compromised in multiple
      sclerosis (MS), different standardized tests are used to detect disseminated
      abnormalities in cardiovascular autonomic functions. sympathetic skin response
      (SSR), a slow wave generated in deep layers of the skin, is induced by reflex
      activation of sudomotor sympathetic efferent fibers. SSR was studied in 70
      patients classified into different categories according to the diagnostic
      criteria for MS. We also obtained pattern reversal visually evoked potentials and
      brainstem auditory evoked potentials as well as somatosensory evoked potentials
      (by median and posterior tibial nerve stimulation). SSR was abnormal in 66
      patients (94.2%), including abnormal foot latency with normal hand latency in 30
      (42.8%), delayed foot and hand latencies in 30 (42.8%), and no response in 6
      (8.6%). The percentages of SSR abnormalities were similar in the different
      patient categories. Pathological SSR were more common than abnormal evoked
      potentials in suspected and probable MS. SSR appears to be a simple and effective
      means of assessing sympathetic sudomotor outflow disturbances in MS, providing a
      valuable addition to current electrophysiological procedures for the detection of
      MS lesions.

PMID- 7823977
TI  - Interaction of glucocorticoids and activity patterns affect muscle function.
AB  - The purpose of this study was to determine the effects of glucocorticoids on
      muscle mass and contractile properties of muscles of similar fiber composition
      but differing in activity patterns. Rats were divided into two groups and
      administered prednisolone (5 mg/kg per day) (P; N = 9) or served as controls (C;
      N = 10) for 10 days. Contractile properties were then determined in the left
      gastrocnemius-plantaris-soleus (GPS) muscle complex and a strip of costal
      diaphragm (D). An index of fatigue was also determined in both muscle
      preparations. Whole-body, GPS, and D weights decreased (P < 0.05) in the P
      animals (22%, 17%, and 15%, respectively) when compared to C. Specific tension
      (PO) increased (P < 0.05) in the GPS complex (21%) and decreased in the D (26%).
      Maximal shortening velocity (Vmax) was not different (P > 0.05) between groups in
      either the GPS or the D. While the index of fatigue was not different (P > 0.05)
      between groups in the D, there was a 30% increase (P < 0.05) in the rate of
      fatigue in the GPS. These data indicate that, although glucocorticoids cause
      decreased muscle mass in both D and GPS, a change in muscle architecture may
      prevent a decrease in force-generating ability in some limb muscles. However,
      glucocorticoids do not increase D fatigability as seen in the GPS.

PMID- 7823978
TI  - Monopolar needle evaluation of paraspinal musculature in the cervical, thoracic,
      and lumbar regions and the effects of aging.
AB  - Motor unit characteristics (phases, turns, amplitude, duration, and area) were
      measured using a monopolar needle and narrowed bandpass (500 Hz to 10 kHz) in
      cervical, thoracic, and lumbar paraspinal muscles in 66 subjects (36 women and 30
      men) aged 22-81 years (mean age 45.7 years). Cervical motor units were of lower
      amplitude and area than thoracic and lumbar motor units (P = 0.0001),
      respectively. The durations of lumbar motor units were longer and larger than
      cervical and thoracic motor units (P = 0.0004). Analysis of covariance of the
      measured characteristics against age showed no significance in the cervical and
      thoracic regions. In lumbar paraspinal motor units, phases and turns increased
      significantly with age (P = 0.044 and P = 0.016, respectively). The increase was
      < 1.0 phase over 30 years. Motor unit amplitude increased with aging (P = 0.055)
      showing an increase of 360 microV over a 30-year time period. It is appropriate
      to assess the number of phases and turns, as well as the duration of the motor
      units in the cervical and thoracic (but not lumbar) spines in addition to seeking
      evidence of spontaneous, single fiber discharges.

PMID- 7823979
TI  - Radiation inhibition of mdx mouse muscle regeneration: dose and age factors.
AB  - A single hind limb was irradiated with 12, 18, 24, or 30 Gy in mdx and C57 mice
      aged 12, 21, or 42 days to determine regeneration inhibition dose-response curves
      in different aged dystrophic mice and to characterize radiation side-effects in
      normal mice. The anterior tibial muscle mass (8 weeks postirradiation) and
      percent central nucleated (i.e., regenerated) muscle fibers were measures of
      regeneration inhibition. Twenty-one-day-old mdx mice irradiated with 18 Gy had
      complete inhibition of muscle regeneration, but 30 Gy only partially blocked
      regeneration in mdx mice irradiated at 12 and 42 days in age. In working to
      produce a clinically relevant model for Duchenne dystrophy, it is crucial to
      regard mouse age as a major factor in determining radiation effects on mdx muscle
      regeneration.

PMID- 7823980
TI  - Function of thick and thin nerve fibers in carpal tunnel syndrome before and
      after surgical treatment.
AB  - Present studies evaluated the functions of thick and thin nerve fibers in carpal
      tunnel syndrome (CTS) to determine whether data of thin nerve fibers can add
      further information to the diagnosis of CTS. Measurements were performed in 22
      patients and 16 age-matched control subjects. Motor and sensory nerve conduction,
      vibratory testing, thresholds of warmth and cold sensations, suprathreshold
      magnitude of pain and flare response, as well as sympathetic reflexes induced by
      noxious mechanostimulation were examined before and 1, 3, 6, 12, and 18 months
      after decompression of the median nerve. Nerve dysfunction in CTS was mainly
      indicated by the electrophysiological parameters of thick myelinated nerve
      fibers. Impairment of thin nerve functions in CTS and postoperative recovery was
      demonstrated by quantitative somatosensory thermotesting. In contrast, assessment
      of flare response and sympathetic reflexes using infrared thermography and
      photoplethysmography did not add further information for the diagnosis of CTS.

PMID- 7823981
TI  - Site and mechanics of failure in normal and dystrophin-deficient skeletal muscle.
AB  - Partial or complete tearing of skeletal muscle occurs both in acute muscle injury
      and in some pathological muscle conditions. Despite the impact of such tearing on
      normal muscle function, few studies have examined the site or mechanism of muscle
      injury at cellular or subcellular levels of organization. The present study
      determines the ultrastructural location and mechanical conditions of tensile
      failure in normal mouse extensor digitorum longus muscles. All of these muscles
      failed near a myotendinous junction (MTJ), but within the muscle fibers, in a
      transverse plane coincident with the edge of an A-band. The breaking stress
      averaged 5.71 x 10(5) N/m2 for muscles stimulated tetanically during lengthening,
      and 5.01 x 10(5) N/m2 for unstimulated muscles. Breaking strain averaged 135%,
      and showed no dependence on the state of activation of the muscle. The energy
      absorbed by each muscle averaged 362.5 mJ/g in unstimulated muscle, and 613.2
      mJ/g in the stimulated samples. In addition to the failure properties of normal
      muscle, the effect of dystrophin deficiency on the site and conditions of failure
      was determined using muscle from mdx mice, which lack dystrophin. The absence of
      dystrophin had no detectable effect on the stress, strain, or energy absorbed,
      regardless of the state of muscle activation. Unstimulated mdx muscle failed in
      the plane of an A-band, but tetanic stimulation produced failure in the reticular
      lamina of the tendon, just external to the MTJ, in 75% of the fibers in the mdx
      muscles. Although dystrophin's cytoplasmic location makes it unlikely that this
      unique mode of failure is due directly to the absence of the protein, failure in
      the reticular lamina may result from a difference in load distribution that
      accompanies the response of mdx muscle to dystrophin deficiency.

PMID- 7823982
TI  - Multiple innervation of muscle fibers in myasthenia gravis.
AB  - Single fiber EMG recordings from patients with myasthenia gravis obtained during
      axonal microstimulation revealed an occasional bimodal distribution of response
      latencies. This phenomenon could be dependent on stimulus strength, however, in a
      way different from that in the axon reflex. It is suggested to be due to dual
      neuromuscular junctions (NMJs) supplied by two different motor neurons. Some
      cases of bimodal jitter were not dependent on stimulus strength and are assumed
      to be due to dual innervation by the same neuron. The phenomenon could only be
      demonstrated at abnormal NMJs with partial impulse blocking. It is suggested to
      reflect multiple reinnervation of muscle fibers that had undergone functional or
      structural denervation in the course of the immune attack against the original
      NMJ. This study suggests that the coexisting NMJs from the same or different
      motor neurons may be functional at the same time.

PMID- 7823983
TI  - Classic neurogenic thoracic outlet syndrome in a competitive swimmer: a true
      scalenus anticus syndrome.
AB  - Neurogenic thoracic outlet syndrome (TOS) is caused by compression of the lower
      brachial plexus usually by a cervical rib or a fibrous band. We describe a 16
      year-old girl with weakness and wasting of her right hand, which progressed over
      the ensuing years. She had been a competitive long distance freestyle and
      butterfly swimmer since age 8 years. A neurological exam at age 20, revealed
      severe atrophy and weakness of all intrinsic right hand muscles, more so of the
      thenar muscles, and hypesthesia along the ulnar aspect of the hand and forearm.
      EMG, which showed a severe chronic axon loss lower trunk brachial plexopathy with
      minimal fibrillations, was typical for classic neurogenic TOS. Chest and cervical
      spine X-rays and MRI of the cervical spine were normal. A supraclavicular
      exploration confirmed the absence of a cervical rib or band. The lower trunk was
      thickened under the scalenus anticus which was sectioned. Neurolysis was also
      done. She was advised to abandon swimming. A clinical and EMG follow-up 2.5 years
      later showed no significant changes. This is the first case of true neurogenic
      TOS caused by scalenus anticus compression occurring in a competitive swimmer.

PMID- 7823984
TI  - Muscle afferent block by intramuscular injection of lidocaine for the treatment
      of writer's cramp.

PMID- 7823985
TI  - Nerve transection without neurotonic discharges during intraoperative
      electromyographic monitoring.

PMID- 7823986
TI  - Muscle AMP deaminase deficiency in 2% of a healthy population.

PMID- 7823987
TI  - "Causalgic" median mononeuropathies: segmental rubror and edema.

PMID- 7823988
TI  - How helpful is thoracic paraspinal EMG in HAM/TSP?

PMID- 7823989
TI  - Polyneuropathy as predominant manifestation of myotonic dystrophy.

PMID- 7823990
TI  - Single fiber EMG and spectral analysis of surface EMG in myotonia congenita with
      or without transient weakness.

PMID- 7823991
TI  - Immunocytochemistry of muscle cytoskeletal proteins in acid maltase deficiency.

PMID- 7823992
TI  - Delayed presentation of a partial palmar ulnar motor neuropathy in a chemist;
      secondary to a rare "occupational hazard".

PMID- 7823993
TI  - Predominantly sensory common peroneal neuropathy.

PMID- 7823994
TI  - Absent F-waves early in the evolution of a spinal cord lesion.

PMID- 7823995
TI  - A comparison of four methods of weaning patients from mechanical ventilation.
      Spanish Lung Failure Collaborative Group.
AB  - BACKGROUND: Weaning patients from mechanical ventilation is an important problem
      in intensive care units. Weaning is usually conducted in an empirical manner, and
      a standardized approach has not been developed. METHODS: We carried out a
      prospective, randomized, multicenter study involving 546 patients who had
      received mechanical ventilation for a mean (+/- SD) of 7.5 +/- 6.1 days and who
      were considered by their physicians to be ready for weaning. One hundred thirty
      patients had respiratory distress during a two-hour trial of spontaneous
      breathing. These patients were randomly assigned to undergo one of four weaning
      techniques: intermittent mandatory ventilation, in which the ventilator rate was
      initially set at a mean (+/- SD) of 10.0 +/- 2.2 breaths per minute and then
      decreased, if possible, at least twice a day, usually by 2 to 4 breaths per
      minute (29 patients); pressure-support ventilation, in which pressure support was
      initially set at 18.0 +/- 6.1 cm of water and then reduced, if possible, by 2 to
      4 cm of water at least twice a day (37 patients); intermittent trials of
      spontaneous breathing, conducted two or more times a day if possible (33
      patients); or a once-daily trail of spontaneous breathing (31 patients).
      Standardized protocols were followed for each technique. RESULTS: The median
      duration of weaning was 5 days for intermittent mandatory ventilation (first
      quartile, 3 days; third quartile, 11 days), 4 days for pressure-support
      ventilation (2 and 12 days, respectively), 3 days for intermittent (multiple)
      trials of spontaneous breathing (2 and 6 days, respectively), and 3 days for a
      once-daily trial of spontaneous breathing (1 and 6 days, respectively). After
      adjustment for other covariates, the rate of successful weaning was higher with a
      once-daily trial of spontaneous breathing than with intermittent mandatory
      ventilation (rate ratio, 2.83; 95 percent confidence interval, 1.36 to 5.89; P <
      0.006) or pressure-support ventilation (rate ratio, 2.05; 95 percent confidence
      interval, 1.04 to 4.04; P < 0.04). There was no significant difference in the
      rate of success between once-daily trials and multiple trials of spontaneous
      breathing. CONCLUSIONS: A once-daily trial of spontaneous breathing led to
      extubation about three times more quickly than intermittent mandatory ventilation
      and about twice as quickly as pressure-support ventilation. Multiple daily trials
      of spontaneous breathing were equally successful.

PMID- 7823996
TI  - The treatment of acute low back pain--bed rest, exercises, or ordinary activity?
AB  - BACKGROUND: Bed rest and back-extension exercises are often prescribed for
      patients with acute low back pain, but the effectiveness of these two competing
      treatments remains controversial. METHODS: We conducted a controlled trial among
      employees of the city of Helsinki, Finland, who presented to an occupational
      health care center with acute, nonspecific low back pain. The patients were
      randomly assigned to one of three treatments: bed rest for two days (67
      patients), back-mobilizing exercises (52 patients), or the continuation of
      ordinary activities as tolerated (the control group; 67 patients). Outcomes and
      costs were assessed after 3 and 12 weeks. RESULTS: After 3 and 12 weeks, the
      patients in the control group had better recovery than those prescribed either
      bed rest or exercises. There were statistically significant differences favoring
      the control group in the duration of pain, pain intensity, lumbar flexion,
      ability to work as measured subjectively, the Oswestry back-disability index, and
      number of days absent from work. Recovery was slowest among the patients assigned
      to bed rest. The overall costs of care did not differ significantly among the
      three groups. CONCLUSIONS: Among patients with acute low back pain, continuing
      ordinary activities within the limits permitted by the pain leads to more rapid
      recovery than either bed rest or back-mobilizing exercises.

PMID- 7823997
TI  - Transesophageal echocardiography in the diagnosis of traumatic rupture of the
      aorta.
AB  - BACKGROUND: Rupture of the aorta is a major cause of death after motor vehicle
      accidents. Survival depends on early diagnosis, and emergency aortography is the
      standard imaging method. Although transesophageal echocardiography is noninvasive
      and can provide high-resolution images of the aorta, information about its value
      in patients with trauma is limited. We conducted this study to assess
      prospectively the value of transesophageal echocardiography in the emergency
      evaluation of patients at risk for aortic injury. METHODS: Transesophageal
      echocardiography of the aorta was attempted in 101 patients admitted to the
      emergency room with a diagnosis of possible traumatic rupture of the aorta.
      Echocardiography and aortography personnel were notified simultaneously of the
      arrival of the patient, and the two tests were performed sequentially by
      operators who were blinded to the results of the other test. The sensitivity and
      specificity of transesophageal echocardiography were calculated on the basis of
      the results of aortography of the arch, surgery, or autopsy. RESULTS:
      Transesophageal echocardiography was attempted in 101 patients. The study was
      successfully performed in 93 patients but could not be completed in 8 because of
      lack of cooperation on the part of the patient (7 patients) or maxillofacial
      trauma (1 patient). Despite a high injury-severity score (mean, 29.6),
      transesophageal echocardiography was performed without complications, and within
      a mean (+/- SD) of 29 +/- 12 minutes. Eleven of the 93 studies (12 percent)
      demonstrated rupture of the aorta near the isthmus. The findings were confirmed
      in 10 of the 11 patients by aortography (9 patients), surgery (9 patients), or
      autopsy (1 patient), yielding a sensitivity of 100 percent and specificity of 98
      percent for the detection of injury to the aorta. There was one false positive
      echocardiogram. CONCLUSIONS: Transesophageal echocardiography is a highly
      sensitive and specific method of detecting injury to the thoracic aorta. This
      technique can be used safely and quickly in critically injured patients with
      suspected traumatic rupture of the aorta and compares favorably with arch
      aortography.

PMID- 7823998
TI  - Brief report: transplantation of cord-blood stem cells into a patient with severe
      thalassemia.

PMID- 7823999
TI  - Images in clinical medicine. Bony metastases.

PMID- 7824000
TI  - Recent advances in radiation oncology.
AB  - Radiotherapy remains an important component of the management of malignant
      disease. Especially when combined with cytotoxic chemotherapy, limited surgical
      excision, or both, irradiation has been shown to control disease in the primary
      site and regional nodes without the need for surgical extirpation as frequently
      as in past years. New developments in three-dimensional treatment planning and
      the precise delivery of high-dose radiation promise to increase the benefit of
      radiation treatment. Finally, molecular studies of the cell's response to
      radiation and the phenomena of DNA damage and repair are providing explanations
      for heretofore unexplained radiobiologic observations. Such research is laying
      the groundwork for targeted manipulation of the cell's response to radiation,
      which will be tested in the near future.

PMID- 7824001
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 4-1995. A 26-year-old woman with recurrent angina after a triple
      coronary-artery bypass graft.

PMID- 7824002
TI  - Weaning from ventilatory support.

PMID- 7824003
TI  - Traumatic rupture of the aorta.

PMID- 7824004
TI  - Insurance and the risk of ruptured appendix.

PMID- 7824005
TI  - Insurance and the risk of ruptured appendix.

PMID- 7824006
TI  - Insurance and the risk of ruptured appendix.

PMID- 7824007
TI  - Insurance and the risk of ruptured appendix.

PMID- 7824008
TI  - C-reactive protein and serum amyloid A protein in unstable angina.

PMID- 7824009
TI  - C-reactive protein and serum amyloid A protein in unstable angina.

PMID- 7824010
TI  - C-reactive protein and serum amyloid A protein in unstable angina.

PMID- 7824011
TI  - Aerosolized corticosteroids for croup.

PMID- 7824012
TI  - Effect of buspirone on urinary catecholamine assays.

PMID- 7824013
TI  - Acute pancreatitis associated with growth hormone therapy for short stature.

PMID- 7824014
TI  - Rapid changes for academic medical centers. 2.

PMID- 7824015
TI  - Concordance for Hodgkin's disease in identical twins suggesting genetic
      susceptibility to the young-adult form of the disease.
AB  - BACKGROUND: Relatives of young adults with Hodgkin's disease are at increased
      risk of Hodgkin's disease, and lines of evidence implicate both inheritance and
      environment. METHODS: We have identified and followed 432 sets of twins affected
      by Hodgkin's disease. The number of cases of Hodgkin's disease observed before
      the age of 50 years in the healthy monozygotic and dizygotic twins of the
      patients with Hodgkin's disease was compared with the number expected from
      national age-specific incidence rates. RESULTS: None of the 187 pairs of
      dizygotic twins became concordant for Hodgkin's disease, whereas 10 of the 179
      pairs of monozygotic twins did; in 5 of these pairs, the second case appeared
      after the original ascertainment. During the observation period, 0.1
      (monozygotic) and 0.1 (dizygotic) cases in the unaffected twins were expected.
      Monozygotic twins of patients with Hodgkin's disease thus had a greatly increased
      risk (standardized incidence ratio, 99; 95 percent confidence interval, 48 to
      182), whereas no increase in the risk for dizygotic twins of patients with
      Hodgkin's was observed. CONCLUSIONS: Genetic susceptibility underlies Hodgkin's
      disease in young adulthood.

PMID- 7824016
TI  - Images in clinical medicine. Cyclic fever in Hodgkin's disease (Pel-Ebstein
      fever)

PMID- 7824017
TI  - Management of occupational exposures to blood-borne viruses.

PMID- 7824018
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 5-1995. A 73-year-old man with focal brain lesions and peripheral
      nerve disease.

PMID- 7824019
TI  - Hodgkin's disease--environmental or genetic?

PMID- 7824020
TI  - Health care reform--past and future.

PMID- 7824021
TI  - Quality of life after myocardial infarction: Canada versus the United States.

PMID- 7824022
TI  - Quality of life after myocardial infarction: Canada versus the United States.

PMID- 7824023
TI  - Quality of life after myocardial infarction: Canada versus the United States.

PMID- 7824024
TI  - Quality of life after myocardial infarction: Canada versus the United States.

PMID- 7824025
TI  - Quality of life after myocardial infarction: Canada versus the United States.

PMID- 7824026
TI  - Quality of life after myocardial infarction: Canada versus the United States.

PMID- 7824027
TI  - Knowledge of drugs for myocardial infarction: generalists versus specialists.

PMID- 7824028
TI  - Knowledge of drugs for myocardial infarction: generalists versus specialists.

PMID- 7824029
TI  - Knowledge of drugs for myocardial infarction: generalists versus specialists.

PMID- 7824030
TI  - Access to specialty care.

PMID- 7824031
TI  - Access to specialty care.

PMID- 7824032
TI  - Access to specialty care.

PMID- 7824033
TI  - Access to specialty care.

PMID- 7824034
TI  - Access to specialty care.

PMID- 7824035
TI  - The effect of light on the vitamin B2 and the vitamin A content of cheese.
AB  - Edam type cheese was exposed to sunlight at ambient temperature and to
      fluorescent light at 5 degrees C. The loss of vitamin B2 (riboflavin) and vitamin
      A was monitored in both the surface and inner layers of the cheese and the
      results compared with control samples kept in the dark. The loss of riboflavin
      when exposed to sunlight was shown to be primarily a surface effect but losses of
      vitamin A were similar throughout the cheese. When exposed to fluorescent light
      at 5 degrees C and monitored at intervals for 10 days the loss of riboflavin was
      still greatest at the surface but a trend to lower values than the control was
      evident throughout the cheese. Vitamin A losses followed a different pattern in
      both sunlight and fluorescent light. There was a heavy initial loss throughout
      the cheese. Under fluorescent light this was followed by a period in which
      further loss was mainly in the surface layer. Vacuum packaging reduced the loss
      of riboflavin but had no effect on the loss of vitamin A.

PMID- 7824036
TI  - A health-sanitary evaluation of lacteal desserts for consumption in Santa Cruz de
      Tenerife.
AB  - The consumption of lacteal desserts in the province of Santa Cruz de Tenerife is
      notably high. However, there are no legal standards in Spain regarding
      microbiological quality. For this reason, we have decided that it would be of
      interest to carry out a health-sanitary study of these products, with the aim of
      discovering their microbial content. 330 samples of lacteal desserts on sale in
      the province of Santa Cruz de Tenerife have undergone analysis. They have been
      divided into three groups: cream caramel (egg and vanilla) (80), mousse (60) and
      the third group, known as "other desserts", which includes custard and the rest
      of lacteal desserts not included in the previous groupings (190). Neither E.
      coli, Salmonella spp., Shigella spp., nor Staphylococcus aureus have been
      detected in any of the samples analysed. In spite of the fact that the results
      obtained do not reflect high microbiological contamination, we consider it
      necessary to lay down legal standards, with reference values, for these lacteal
      products, which will guarantee good microbiological quality.

PMID- 7824037
TI  - 5-Hydroxytryptamine (5-HT) and the initiation of migraine: new perspectives.
AB  - The hypothesis that 5-hydroxytryptamine (5-HT) acting through 5-HT2C receptors is
      a key factor in the initiation of migraine has been re-evaluated in the light of
      recent basic and clinical scientific developments. The key findings are that
      nitric oxide is an important trigger for migraine, that 5-HT2B/5-HT2C receptors
      are present on endothelial cells and trigger nitric oxide release when activated
      and that supersensitivity of the 5-HT2B/5-HT2C receptor is a neurochemical
      feature predisposing to headache. Taken together the data bring new perspectives
      to the role of 5-HT acting through 5-HT2C (or closely similar) receptors in the
      initiation of migraine.

PMID- 7824038
TI  - CGP 25454A, a novel and selective presynaptic dopamine autoreceptor antagonist.
AB  - N-(diethylamino-ethyl)-4-chloro-5-cyano-2-methoxy-benzamide-hydrochlo rid e (CGP
      25454A) is a new benzamide derivative now in clinical trials in patients with
      major depression. Here we describe some basic neurochemical and behavioural
      properties in animal experiments. In vitro, CGP 25454A increased the field
      stimulated [3H]- and [14C]-overflow from rat striatal slices preloaded with
      [3H]dopamine and [14C]choline, indicating that CGP 25454A was able to enhance the
      release of both dopamine (DA) and acetylcholine (ACh). However, CGP 25454A was
      12.9 times more potent in increasing, by 1/6 of the apparent maximal increase,
      the release of [3H]DA than that of [14C]ACh. In vivo, CGP 25454A increased
      [3H]spiperone binding to receptors of the D2 family in rat striatum by 90-110%
      (ED50: 13 mg/kg i.p.). As a similar increase in [3H]spiperone binding was found
      with a variety of agents which increase the synaptic concentration of endogenous
      DA, the effect of CGP 25454A most probably reflects an enhanced release of DA
      under in vivo conditions. At 30-100 mg/kg, CGP 25454A inhibited [3H]spiperone
      binding in the pituitary of the same animals as a result of a blockade of
      postsynaptic DA receptors. This dual mode of action was also apparent in terms of
      behavioral changes. At doses as low as 5-10 mg/kg, CGP 25454A produced a weak
      stimulation, suggested by a trend of increased spontaneous rearing and
      corroborated by a significant potentiation of the elevated rearing induced by (+)
      amphetamine. By contrast, at doses of 30-100 mg/kg, it exerted clear-cut sedative
      and neuroleptic-like properties.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7824039
TI  - Halothane anesthesia enhances the effect of dopamine uptake inhibition on
      interstitial levels of striatal dopamine.
AB  - The anesthetic, isoflurane, has been shown to potentiate the ability of the
      dopamine (DA)-uptake inhibitor, nomifensine, to increase the brain interstitial
      dopamine level ([DA]e). Since the effect of the more commenly used anesthetic,
      halothane, on this system is unknown, we determined [DA]e by microdialysis in the
      striatum of rats, conscious or anesthetized with halothane, in the presence of
      the more selective DA uptake inhibitor, vanoxerine (GBR 12909), or the DA
      releaser, d-amphetamine. Basal [DA]e was not changed by halothane. However, in
      halothane-anesthetized rats, the vanoxerine (3 mg/kg i.v.)-induced DA response
      increased severalfold compared to the response in conscious rats. The initial
      peak response to d-amphetamine (1 mg/kg i.v.) did not change, but the late
      response (1-3 h after injection) was augmented in anesthetized rats. Halothane is
      believed to increase firing of DA neurons in the substantia nigra and, hence, to
      release striatal DA. We hypothesize that [DA]e is maintained at a normal level
      during the increased firing by equally increased activity of the DA transporter.
      However, when the DA transporter is blocked by vanoxerine, the increased DA
      release is unimpaired and [DA]e rises.

PMID- 7824040
TI  - Effects of MPP+ on catecholamine levels in adrenal glands and heart of rats.
AB  - The effects of MPP+ (2.5-20 mg/kg) on the adrenal glands and heart were
      investigated in rats. At various periods after s.c. drug administration the rats
      were decapitated and tissue catecholamine levels were determined by means of HPLC
      with electrochemical detection. Adrenal dopamine (DA) levels were reduced at 2-8
      h after MPP+ administration, but this decrease was followed by an elevation after
      16 h and return to the control values after one week. Three successive injections
      of MPP+ caused a statistically significant elevation in adrenal DA, one day, with
      a tendency to elevation four and seven days after the last injection, whereas a
      severe (up to 96%) decrease in heart noradrenaline (NA) was found one day after
      the last injection. Seven days after the last injection a 50% depletion of NA in
      the heart was still observed. Pretreatment with GBR 12909 (30 mg/kg, 4h) blocked
      the MPP+ (10 mg/kg, 2 h) induced reduction of adrenal DA levels, but at the same
      time GBR 12909 failed to block the effects of MPP+ in the heart. One day after
      three successive daily injections of MPP+ (10 mg/kg each), the DA-uptake
      inhibitor GBR 12909 (30 mg/kg, 6 h) could still induce an increase in adrenal DA.
      MPP+ appears to lack persistent cytotoxic action in the adrenal medulla but
      rather to cause a transient inhibition of DA synthesis followed by a compensatory
      stimulation. The inhibition can be blocked by specific inhibitor of the DA-uptake
      mechanism, suggesting a direct effect of MPP+ taken up by adrenomedullary
      cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7824042
TI  - Modulation of electrically evoked [3H]-noradrenaline release from cultured chick
      sympathetic neurons.
AB  - In the present study we attempted a comprehensive characterization of modulation
      of noradrenaline release from chick sympathetic neurons. To this purpose
      sympathetic neurons derived from chick lumbosacral paravertebral ganglia and kept
      in culture for 7 days were loaded with 0.05 mumol/l [3H]-noradrenaline and
      subjected to electrical field stimulation (36 pulses/3 Hz). Since the released
      transmitter was partially recaptured, superfusion was usually performed in the
      presence of (+)-oxaprotiline, an inhibitor of noradrenaline re-uptake. [3H]
      Noradrenaline was released in a manner which was dependent on extracellular Ca2+
      and sensitive to tetrodotoxin (TTX). omega-Conotoxin (omega-CTX; 100 nmol/l)
      abolished [3H]-noradrenaline release indicating that influx through omega-CTX
      sensitive Ca(2+)-channels was essential for transmitter release. 1,4-dihydro-2,6
      dimethyl-5-nitro-4-[2- (trifluoromethyl)-phenyl]-3-pyridine carboxylic acid
      methyl ester ((+/-) Bay K 8644) and 4-(4-benzofurazanyl)-1,4-dihydro-2,6-
      dimethyl-3-nitro-5-pyridinecarboxylic acid isopropyl ester ((+)-202-791),
      agonists at L-type voltage sensitive Ca(2+)-channels (VSCCs), increased
      noradrenaline release and induced, in addition, an overflow of tritium which was
      Ca(2+)-dependent and prevented by the presence of TTX. The L-type VSCC
      antagonists (-)-202-791 and (+)-4-(4-benzofurazanyl)-1,4-dihydro-2,6-dimethyl-3,5
      pyridinedicar boxylic acid methyl, isopropyl ester) ((+)-PN 200-110) diminished
      [3H]-noradrenaline release. These data suggest that L-type VSCCs, probably
      located on the cell body of the neuron, play an additional role in modulation of
      release.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7824041
TI  - [3H]idazoxan binding to bovine adrenal medullary membranes: identification and
      pharmacological characterization of I2-imidazoline sites.
AB  - Bovine adrenal chromaffin cells, which have been shown to lack alpha 2
      adrenoceptors, were used to investigate the pharmacological characteristics of
      [3H]idazoxan binding sites. The binding of [3H]idazoxan was very rapid,
      reversible, partly specific (as defined by cirazoline 0.1 mmol/l; 50% specific
      binding at [3H]idazoxan 10 nmol/l), saturable and of high affinity (KD 13nmol/l)
      and, hence, was compatible with the criteria for the identification of an
      imidazoline binding site (IBS). Since in competition experiments rauwolscine and
      (-)-adrenaline showed only negligible affinity for these adrenal medullary
      binding sites, the lack of alpha 2-adrenoceptors was confirmed. Histamine and
      amiloride also did not inhibit [3H]idazoxan binding or caused only negligible
      inhibition. In contrast, the specific binding of [3H]idazoxan was concentration
      dependently inhibited by several imidazolines and guanidines with the following
      rank order of potency which conforms to the characteristics of the previously
      defined I2-IBS (in parentheses: Ki, nmol/l): idazoxan (4) = cirazoline (4) >>
      clonidine (272) = BDF 6143 (299; 4-chloro-2-(2-imidazoline-2-ylamino)
      isoindoline) > BDF 6100 (563; 2-(2-imidazolin-2-yl-amino)-isoindoline) > or = BDF
      7579 (868; (4-chloro-2-isoindolinyl)guanidine) > phentolamine (1424) =
      naphazoline (1451). Equilibrium [3H]idazoxan binding was reduced by K+ but not by
      Na+ or the non-hydrolysable GTP-analogue Gpp(NH)p (5'-guanylylimidodiphosphate;
      100 mumol/l). In conclusion, membranes of the bovine adrenal medulla are endowed
      with non-adrenergic high-affinity [3H]idazoxan sites which exhibit the
      pharmacological properties of the amiloride-insensitive subtype of I2-IBS and
      probably are not coupled to a G-protein.

PMID- 7824044
TI  - Studies on the pharmacological interventions to prevent oxygen free radical (OFR)
      mediated toxicity; effects of dopexamine, a DA1 receptor and beta 2 adrenoceptor
      agonist.
AB  - We have previously demonstrated that the lethal effects of free radicals
      generated by intravenous administration of Xanthine (X: 0.225 mg kg-1) and
      Xanthine Oxidase (XO: 5 u kg-1) were prevented by calcium channel blockers such
      as felodipine (a dihydropyridine calcium antagonist) and verapamil. These studies
      have implicated that there may be potential interactions between free radicals
      and cell calcium. However, alternate mechanisms such as hemodynamic changes in
      the overall effects of calcium antagonists cannot be ruled out. Therefore, the
      present studies are conducted to further investigate the efficacy of various
      cardiovascular agents such as Dopexamine (DPX) on [X+XO]-induced mortality.
      Intravenous administration of [X+XO] to anesthetized rats produced a rapid
      decrease in blood pressure and a mortality rate of over 90%. Pretreatment with
      dopexamine, a dopamine receptor (DA1) and beta 2 adrenoceptor agonist
      significantly enhanced survival upto 70%. Neither dobutamine nor prenalterol,
      (preferential beta 1 agonists) both of which produced similar increases in heart
      rate as DPX, enhanced survival rate thus suggesting that cardiac stimulation
      alone, did not contribute to the protective effects of DPX. Likewise, fenoldopam,
      a DA1 agonist and a vasodilator also failed to have any significant protective
      effect on [X+XO]-induced mortality suggesting that the DA1 receptor activation
      alone cannot account for the salutary effects of dopexamine. Pretreatment of the
      rats with Salbutamol, a preferential beta 2 agonist significantly enhanced
      survival upto 50% and a beta 2 antagonist ICI 118,551 significantly attenuated
      the ability of dopexamine to promote survival.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7824043
TI  - Receptor crosstalk: effects of prolonged carbachol exposure on beta 1
      adrenoceptors and adenylyl cyclase activity in neonatal rat ventricular myocytes.
AB  - Supersensitivity of adenylyl cyclase after exposure to inhibitory agonists is a
      general means of cellular adaptation. We hypothesized that such "crosstalk"
      between muscarinic cholinergic agonists, beta 1-adrenoceptors, and adenylyl
      cyclase may be an important mechanism of cardiac adaptation to interventions that
      enhance vagal activity. We used primary cultures of neonatal rat ventricular
      myocytes and measured beta-adrenoceptors by radioligand binding and adenylyl
      cyclase activity by a single column method. Carbachol induced a time- and dose
      dependent reversible decrease in cell surface beta 1-adrenoceptors. The peak
      effect occurred after 20 h of exposure to 100 microM carbachol which caused a
      decrease in the maximum number of binding sites for the beta-adrenoceptor
      antagonist 3H-CGP-12177 from 42.3 +/- 3.4 to 33.0 +/- 2.6 fmol/mg protein (n =
      12, P < 0.03) without a change in antagonist affinity. Loss of cell surface
      receptors was prevented by atropine and by the protein kinase C inhibitor H7. The
      decrease in cell surface receptors was not accompanied by receptor
      internalization as assessed by equilibrium binding experiments in a cytosolic
      fraction using 125I-iodocyanopindolol. In contrast to the well-known acute
      inhibitory effects of carbachol on adenylyl cyclase activation, prolonged
      carbachol exposure preserved (-)-isoprenaline-stimulated adenylyl cyclase
      activity and enhanced postreceptor stimulated adenylyl cyclase activity.
      Carbachol did not further enhance adenylyl cyclase activity after pretreatment
      with pertussis toxin. The protein kinase C inhibitor chelerythrine prevented the
      carbachol induced enhancement of forskolin-stimulated adenylyl cyclase activity.
      We conclude that prolonged incubation with carbachol in rat neonatal ventricular
      myocytes causes a reduction in cell surface beta 1-Adrenoceptor density. beta 1
      Adrenoceptor-mediated adenylyl cyclase activity is preserved and postreceptor
      mediated adenylyl cyclase activity is augmented. Our data suggest that carbachol
      stimulated protein kinase C activity may play a key role in the prolonged
      muscarinic regulation of adenylyl cyclase activity.

PMID- 7824045
TI  - Identification and characterization of isoenzymes of cyclic nucleotide
      phosphodiesterase in human kidney and heart, and the effects of new cardiotonic
      agents on these isoenzymes.
AB  - The present study was done to identify and characterize the isoenzymes of cyclic
      nucleotide phosphodiesterase (PDE) and to determine their intracellular
      distribution in human kidney and heart. The in vitro effects of new cardiotonic
      agents, namely, NSP-805 (4,5-dihydro-5-methyl-6-[4-[(2-methyl-3-oxo-1
      cyclopentenyl)amino] phenyl]-3(2H)-pyridazinone), TZC-5665 (6-[4-[2-[3-(5-chloro
      2-cyanophenoxy)-2-hydroxypropylamino]- 2 -methylpropylamino]phenyl]-5-methyl-4,5
      dihydro-3(2H)-pyridazinone ) and its metabolites, OPC-18790 ((+/-)-6-[3-(3,4
      dimethoxybenzylamino)-2 -hydroxypropoxy]-2-(1H)-quinolinone), MS-857 (4-acetyl-1
      methyl-7-(4-pyridyl)-5,6,7,8-tetrahydro-3(2H)-isoquinolinone ) and E-1020 (1,2
      dihydro-6-methyl-2-oxo-5-(imidazo[1,2-a]pyridin-6-yl)-3-pyridine carbonitrile
      hydrochloride monohydrate), on these human PDE isoenzymes were also investigated.
      PDE isoenzymes were separated from cytosolic and particulate fractions of
      homogenates of human kidney and heart by DEAE-Sepharose chromatography. PDE
      isoenzymes were identified by their elution characteristics, substrate
      specificities, sensitivities to regulation by effectors and by the use of
      isoenzyme-specific inhibitors. In a cytosolic fraction from kidney,
      Ca2+/calmodulin-dependent PDE (CaM-PDE), cyclic GMP-stimulated PDE (cGS-PDE),
      cyclic GMP-inhibited PDE (cGI-PDE) and two forms of cyclic AMP-specific PDE (cAMP
      PDE) were resolved. One form of cAMP-PDE (cAMP-PDE alpha), which was eluted at a
      lower ionic strength than cGI-PDE during DEAE-Sepharose chromatography, was newly
      recognized in human tissues, though the other form (cAMP-PDE beta), which eluted
      later than cGI-PDE, had been previously isolated.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7824046
TI  - The effect of cyclopyrrolones on GABAA receptor function is different from that
      of benzodiazepines.
AB  - The effects of the cyclopyrrolones zopiclone and suriclone on the function of the
      central gamma-amino-butyric acid type A (GABAA) receptor complex in mouse brain
      were evaluated both in vitro and in vivo. Added in vitro to mouse cerebral
      cortical membranes, these compounds potently inhibited [3H]flumazenil binding
      with IC50 (50% inhibitory concentration) values of 35.8 nM (zopiclone) and 1.1 nM
      (suriclone). Similar results were obtained with cerebellar membranes, indicating
      that these drugs do not discriminate between putative type I and type II
      benzodiazepine receptors. The interaction of cyclopyrrolones with recognition
      sites present at the level of the GABA receptor complex appears to be
      competitive, because zopiclone decreased the affinity of the receptors for
      [3H]flumazenil without affecting the maximal number of binding sites. Moreover,
      zopiclone and suriclone did not affect the rate of dissociation of [3H]flumazenil
      from benzodiazepine receptors. The in vitro efficacy of zopiclone appeared
      different from that of suriclone and the benzodiazepines diazepam and
      flunitrazepam. Thus, zopiclone failed to affect muscimol-stimulated 36Cl- uptake
      and only slightly inhibited t-[35S]butylbicyclophosphorothionate ([35S]TBPS)
      binding. In contrast, like diazepam and flunitrazepam, suriclone increased
      muscimol-stimulated 36Cl- uptake and markedly inhibited [35S]TBPS binding. In
      contrast, like diazepam and flunitrazepam, suriclone increased muscimol
      stimulated 36Cl- uptake and markedly inhibited [35S]TBPS binding. On the other
      hand, suriclone, like zopiclone, did not modify [3H]muscimol binding to mouse
      cerebral cortical membranes. Moreover, zopiclone antagonized the reduction in
      [35S]TBPS binding elicited by the benzodiazepine receptor full of agonist
      diazepam. Consistent with its low efficacy in vitro, oral administration of
      zopiclone (2.5 to 100 mg/kg, p.o.) in mice failed to modify [35S]TBPS binding
      subsequently measured in cerebral cortical membranes "ex vitro".(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7824047
TI  - Binding sites for [125I]-Bolton-Hunter scyliorhinin II in guinea-pig ileum: a
      radioligand binding, functional and autoradiographic study.
AB  - Binding of the tachykinin NK-3 receptor-preferring radioligand [125I]-Bolton
      Hunter scyliorhinin II (BHSCYII) was investigated in membranes from guinea-pig
      ileum muscularis externa with myenteric plexus (MMP). Specific binding for
      BHSCYII was saturable and reversible. Curvilinear Scatchard plots and biphasic
      competition data indicate binding to two classes of sites (0.8 nM, 8% of sites;
      340 nM, 92% of sites). Competition-binding data was ambiguous with the rank order
      of potency neuropeptide K (NPK) > substance P (SP) congruent to [Sar9,Met(O2)11]
      SP congruent to [pGlu6,Pro9]SP(6-11) (septide) > neuropeptide gamma (NP gamma) >
      kassinin congruent to physalaemin > neurokinin A (NKA) > SCYII > neurokinin B
      (NKB). Senktide, eledoisin, [Lys5,MeLeu9,Nle10]-NKA(4-10), CP 96345, RP 67580,
      MDL 29913, SR 48968 and Gpp[NH]p were ineffective competitors, suggesting a lack
      of binding to conventional NK-1, NK-2 or NK-3 receptors. Competition curves for 5
      agonists could be resolved into two sites, with no competitor showing outstanding
      affinity. Autoradiographic studies revealed moderate BHSCYII binding to myenteric
      plexus ganglia, unaffected by co-incubation with CP 96345 or with senktide. These
      data suggest a component of BHSCYII binding at unusual NPK/SP-preferring sites on
      ganglia. [Sar9,Met(O2)11]-SP was the most potent contractile agonist of the
      isolated ileum, followed by SCYII, NP gamma, senktide and NPK, with
      [Lys5,MeLeu9,Nle10]-NKA(4-10) least potent. Contractions elicited by senktide
      were entirely neurogenic. Responses to SCYII were partly sensitive to
      tetrodotoxin, atropine and CP 96345, indicative of action at both neuronal
      receptors and smooth muscle NK-1 receptors. The NK-2 antagonist SR 48968 did not
      alter responses to SCYII, [Sar9,Met(O2)11]-SP or senktide.

PMID- 7824048
TI  - Electrophysiologic and inotropic effects of O-benzyl-phosphocreatine in rabbit
      myocardium.
AB  - O-benzyl-phosphocreatine-Na (BPC) applied in superfusion increased the action
      potential amplitude and isometric tension in the isolated sinus node strips,
      atrial trabeculae and papillary muscles. BPC enhanced the slope of the slow
      diastolic depolarization evoking the positive chronotropic effect. The drug
      prolonged the action potential duration in the atrial and ventricular cells. BPC
      exerted similar effects during hypoxia and cyanide superfusion in the working
      myocardium. On the other hand, phosphocreatine as well as O-benzyl
      phosphoglycocyamine added to the superfusion fluid were ineffective. BPC
      increased also the ATP content of the superfused contracting atrial trabeculae.
      These results suggest that BPC crosses the sarcolemma, elevates the ATP content,
      and thereby it increases the slow inward and can serve as an additional source of
      the metabolic energy in the cardiac cells.

PMID- 7824049
TI  - Influence of calcium on the effects of okadaic acid and its interaction with
      caffeine and theophylline in rat myometrium.
AB  - The effects of okadaic acid (OA), a monocarboxylic acid produced by marine
      dinoflagellates belonging to the genera Dinophysis and Prorocentrum, and their
      interactions with theophylline and caffeine were studied on the rat-isolated
      uterus in a calcium-containing medium and a calcium-free medium in the presence
      of 10(-3) M EGTA. Okadaic acid (5 x 10(-6) to 5 x 10(-5) M) induced a
      concentration-dependent contraction of the rat-isolated uterus corresponding,
      with 5 x 10(-5) M, to 142.3 +/- 6.1% (n = 7) of the contraction induced by
      oxytocin 10(-6) M. The time to peak tension was inversely proportional to the
      maximum effect produced. The contraction was not sustained and was followed by a
      concentration-dependent decrease in tone. In a Ca(2+)-free medium containing 10(
      3) M EGTA the contractile effects of OA were significantly inhibited or reduced.
      A 30 min pretreatment with theophylline (3 x 10(-3) M) or caffeine (2 x 10(-2) M)
      significantly reduced, in a Ca(2+)-containing medium, the maximum contractile
      effect of OA 10(-5) and/or 2 x 10(-5) M and shortened the relative time to peak
      tension. In a Ca(2+)-free medium containing 10(-3) M EGTA, only the second effect
      was observed. With a 1 min pretreatment and in a Ca(2+)-containing medium,
      theophylline 3 x 10(-3) M and caffeine 10(-2) M did not modify the maximum effect
      of OA 10(-5) M but shortened the time to peak tension.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7824050
TI  - Effects of type I-interferons on human thyroid epithelial cells derived from
      normal and tumour tissue.
AB  - Long term interferon (IFN) therapy is frequently associated with side effects
      which affect the thyroid gland such as hypothyroidism and thyroiditis. We have
      therefore tested the ability of type I-IFNs to exert direct effects on primary
      cultures of human thyroid epithelial cells: (i) Type I-IFNs (IFN-alpha 2b and IFN
      omega) inhibit cell proliferation as determined by [3H]thymidine incorporation
      with a half-maximal effect at approximately 1 ng/ml (50 pM). Inhibition of cell
      growth is observed in cells derived from normal thyroid as well as neoplastic
      tissue (autonomous and non-secreting adenoma; follicular, papillary and
      anaplastic carcinoma). (ii) Over a similar concentration range, type I-IFNs
      suppressed thyroglobulin release by thyroid cells. (iii) IFN-alpha 2b stimulated
      surface expression of major histocompatibility class (MHC) I but not MHC II
      molecules, while IFN-gamma enhanced the expression of both MHC I and MHC II
      molecules. This effect of IFN-gamma, but not that of IFN-alpha 2b was antagonized
      by suramin. (iv) Incubation of thyroid cells with IFN-alpha 2b also resulted in
      increased cell surface levels of the intercellular adhesion molecule 1 (ICAM-1).
      These findings demonstrate that type I-IFNs directly affect thyroid function and
      explain related side effects of these cytokines. In addition, our results provide
      a rational basis for the possible use of type I-IFNs in the treatment of patients
      with advanced thyroid cancer for whom no therapeutic alternative exists.

PMID- 7824051
TI  - Lack of long-term effects after beta-amyloid protein injections in rat brain.
AB  - Rat beta(1-42) peptide (beta/A4) or phosphate buffered saline (PBS) was
      bilaterally injected into the hippocampus (HIP) or the lateral ventricle (ICV) of
      3-month-old Fischer-344 rats. Fifteen months later, the animal's ability to learn
      a spatial memory task was tested using the Morris water maze. Acquisition of the
      task was impaired by the bilateral injection of either peptide or PBS into the
      hippocampus. Hippocampal-injected animals showed an increased average latency to
      find the platform by approximately 6 s (p < 0.05). However, injection of rat beta
      peptide into the hippocampus or lateral ventricles failed to induce behavioral
      impairment when compared to vehicle injected controls. Retention of this task was
      not significantly impaired in any group. The spatial acuity test, a trial without
      the platform, revealed that both groups of animals that received hippocampal
      injections were impaired, spending 23% less time in the target quadrant compared
      to ICV-injected animals (p < 0.005). Hippocampal ChAT activity was decreased in
      beta/A4-injected animals but not significantly (p < 0.06). beta/A4
      immunoreactivity was detected at the bottom of the needle track and the adjacent
      parenchyma of beta/A4 hippocampal-injected animals after 16 months. However, long
      term in vivo deposition of beta/A4 in both regions did not result in an
      upregulation of hippocampal amyloid precursor protein (APP) expression and there
      was no qualitative neuronal loss in the hippocampus.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7824052
TI  - Decreased levels of C1q in cerebrospinal fluid of living Alzheimer patients
      correlate with disease state.
AB  - Recent reports that complement proteins comprising the classical pathway are
      associated with senile plaques suggest that activation of the classical
      complement cascade in Alzheimer's disease tissue results in bystander cell lysis
      and may contribute to AD neuropathology. Analysis of cerebrospinal fluid may
      prove to be a useful means of detecting changes in immunological activity in the
      brain. We use an enzyme-linked immunosorbent assay to measure levels of C1q, a
      subunit of the classical complement cascade, in the CSF of patients clinically
      diagnosed with possible or probable AD. Significantly lower levels of C1q were
      detected in the CSF of the Alzheimer group as compared to control CSF [AD: mu =
      268 ng/ml, SD = 84; non-AD: mu = 340 ng/ml, SD = 76; F(1, 44) = 5.84, p = 0.02].
      Diminished performance on global measures of mental status such as the Mini
      Mental State Exam (R = 0.45; p = 0.0072) and Blessed's Information, Memory, and
      Concentration test (R = 0.42; p = 0.0138) showed high correlations with decreased
      C1q levels. More specific measures of cognitive function, such as word recall (R
      = 0.42; p = 0.012), word recognition (R = 0.52; p = 0.0017) and delayed recall (R
      = 0.45; p = 0.0062) memory tasks also correlated strongly with decreased C1q
      levels.

PMID- 7824053
TI  - Neurofibrillary tangles have no obligatory predilection for acetylcholinesterase
      rich neurons.
AB  - Parts of the brain that are prone to NFT formation normally contain many neurons
      that are intensely acetylcholinesterase (AChE)-positive. In this study, we used
      thioflavin-S immunofluorescence, AChE histochemistry, and AChE
      immunocytochemistry to investigate the possibility that intense AChE positivity
      may act as a perikaryal marker for the vulnerability to NFT formation. Our
      observations in entorhinal and motor cortices and in the subthalamic nucleus
      demonstrate major mismatches between the distribution of AChE-rich neurons in
      normal brains and the distribution of NFT in AD. There is therefore no obligatory
      relationship between intense AChE positivity in the premorbid period and
      subsequent vulnerability to tangle formation.

PMID- 7824054
TI  - Apolipoprotein E-immunoreactivity in aged rhesus monkey cortex: colocalization
      with amyloid plaques.
AB  - In the present study, we examined the relationship between ApoE and amyloid
      containing profiles within the cerebral cortex of young, middle aged, and aged
      Rhesus monkeys. Polymerase chain reaction analysis revealed a pattern consistent
      with the ApoE e4 phenotype in the rhesus monkey similar to that reported in
      humans. We found numerous ApoE immunoreactive plaques within the temporal
      neocortex and amygdala, whereas the hippocampus contained only a few such
      plaques. Although virtually all ApoE-immunoreactive plaques coexpressed beta
      amyloid, most plaques were beta A4 positive/ApoE immunonegative within the aged
      monkey cortex. Moreover, we observed a close correspondence between ApoE and
      thioflavin-positive (i.e., amyloid) plaques suggesting that ApoE may play a
      critical role in the conversion of beta A4 to its beta-pleated form. Because
      ApoE, beta A4 and amyloid are expressed in plaques within the aged Rhesus macaque
      cortex, this species may provide an in vivo model for investigations aimed at
      clarifying the interactions between these proteins in normal and pathologic
      aging.

PMID- 7824055
TI  - Reduced bicuculline response and GABAA agonist binding in aged rat hippocampus.
AB  - Extracellular field recordings from CA1 pyramidal cells in the rat hippocampal
      slice preparation were used to examine the effects of age on gamma-aminobutyric
      acid (GABA)-mediated recurrent inhibition. The actions of bicuculline (1-100
      microM), a GABAA antagonist, were assessed in slices from young (1-3 months) and
      aged (26 months) Fischer 344 rats. Pre-drug population spike amplitudes were
      smaller in slices from aged rats. Bicuculline increased population spike
      amplitudes in slices from both age groups, but slices from young rats were more
      sensitive to the antagonist. Bicuculline also produced multiple population spikes
      in slices from both age groups, however the increase in population spike burst
      durations was much greater in slices from young rats than in slices from aged
      rats. Agonist radiolabeled GABAA binding site density was significantly decreased
      in hippocampal tissue from aged rats. Our results suggest there is a reduction in
      GABAergic inhibition in hippocampal slices from aged rats, possibly mediated by a
      decrease in GABAA receptors.

PMID- 7824056
TI  - Effect of 5-hydroxytryptophane on behavior and hippocampal physiology in young
      and old rats.
AB  - Spatial memory ability, tested in a water maze, was severely impaired in control,
      24-month-old hooded rats. A daily injection of the serotonin precursor, 5
      hydroxytryptophane (5-HTP), prior to training sessions, had no effect on the
      behavior of the young rats but improved considerably the performance of the old
      rats in the watermaze. In the same groups of young and aged rats, the response
      properties of the hippocampal dentate gyrus to perforant path stimulation was
      assessed before and after parenteral administration of 5-HTP. The dentate gyrus
      of aged rats produces a smaller EPSPs in response to perforant path stimulation
      but a larger population spike for a given EPSP than that produced in young rat
      brains. These differences are not affected by 5-HTP. In young brains, priming
      commissural stimulation suppresses subsequent reactivity to perforant path
      stimulation. This priming effect is nearly absent in aged rat hippocampus but
      reappears when the rat is injected with 5-HTP. It is suggested that the
      serotonergic innervation of the rat hippocampus plays a major role in regulation
      of the excitability of the hippocampus and in behavioral functions associated
      with this structure.

PMID- 7824057
TI  - Endogenous inhibitors of human choline acetyltransferase present in Alzheimer's
      brain: preliminary observation.
AB  - We have previously demonstrated the presence in Alzheimer's disease brain of an
      endogenous inhibitor of choline acetyltransferase activity. Selected properties
      of these compounds were investigated. There appear to be two distinct classes of
      inhibitor present, both phosphomonoesters and nonphosphorylated substances. They
      are not proteins, pass through 500 mm dialyses membranes and are not lipoidal.
      There are both different sensitivities of individual control cytosotic activity
      to inhibition and differences in intrinsic inhibitory activity present in
      individual Alzheimer's disease brain samples. There is a competitive type of
      inhibition with respect to acetyl CoA as substrate and a noncompetitive type with
      respect to choline as substrate.

PMID- 7824058
TI  - Regional changes in expression of NCAM, GFAP, and S100 in aging rat brain.
AB  - In aging brain degenerative processes occur. However, the aging brain still have
      regenerative capacity although diminished compared to young rats. The neural cell
      adhesion molecule (NCAM) may be involved in neuroplasticity during regenerative
      events. In this study, the polypeptide composition and amount of NCAM was
      determined in regions of brain from young, mature and old rats. During adult
      life, the amount of NCAM decreased in several brain regions whereas in aged rats,
      NCAM was enhanced in all brain regions examined. The amount of the glial
      fibrillary acidic protein (GFAP) increased during aging in all brain regions
      reflecting general gliosis in the aged rat brain. The amount of the neuro- and
      gliotrophic protein S100 increased from young adult to mature age in all brain
      regions investigated followed by a decrease during old age. Aged rats were tested
      in a Morris water maze and a group of rats (20%) with learning impairment was
      defined. However, no differences in amount of NCAM, GFAP, or S100 were observed
      between aged rats with and without spatial learning impairment.

PMID- 7824059
TI  - Effects of chronic dietary aluminum on local cerebral glucose utilization in
      rats.
AB  - Beginning at 4 weeks of age normal, male, Sprague-Dawley rats were reared on
      Purina Laboratory Chow and drinking water containing 100 microM AlCl3. After 2
      years, local rates of cerebral glucose utilization were determined with the
      autoradiographic [14C] deoxyglucose method in the brain as a whole and in 25
      brain regions in 6 treated rats and 4 age-matched controls. The results indicate
      that any effects of chronic aluminum in the diet on rates of cerebral glucose
      utilization are small. In the brain as a whole, the mean rate of glucose
      utilization in the aluminum-treated rats was 6% lower than that of the controls
      (p = 0.09). In 21 of the 25 brain regions examined mean rates of glucose
      utilization were generally lower in the aluminum-treated rats but in none of the
      region were the effects statistically significant.

PMID- 7824060
TI  - Progress in the diagnosis of Alzheimer's disease.

PMID- 7824061
TI  - Effect of dichloroacetate on acetyl-CoA content and acetylcholine synthesis in
      rat brain synaptosomes.
AB  - In potassium-depolarized synaptosomes Ca2+ inhibited oxidation of pyruvate (30%)
      and decreased the level of acetyl-CoA in intrasynaptosomal mitochondria (32%). On
      the other hand, Ca2+ facilitated provision of acetyl-CoA to synaptoplasm, since
      under these condition no change of synaptoplasmic acetyl-CoA and twofold
      stimulation of acetylcholine synthesis were found. However, in Ca(2+)-activated
      synaptosomes both synaptoplasmic acetyl-CoA and acetylcholine synthesis were
      suppressed by 1 mM (-)hydroxycitrate by 27 and 29%, respectively. It was not the
      case in resting synaptosomes. Dichloroacetate (0.05 mM) partially reversed the
      inhibitory effect of Ca2+ on pyruvate metabolism in synaptosomes and whole brain
      mitochondria. In Ca(2+)-stimulated synaptosomes, the dichloroacetate overcame
      suppressive effects of (-)hydroxycitrate on the level of synaptoplasmic acetyl
      CoA and acetylcholine synthesis, but not on citrate cleavage. It is concluded
      that dichloroacetate may improve the metabolism of acetylcholine in activated
      cholinergic terminals by increasing the production of acetyl-CoA in mitochondria
      and increasing its provision through the mitochondrial membrane to synaptoplasm
      by the transport system, independent of the ATP-citrate lyase pathway.

PMID- 7824062
TI  - Topology of Wolfgram proteins and 2', 3'-cyclic nucleotide 3'-phosphodiesterase
      in CNS myelin: studies with proteases.
AB  - The topological disposition of Wolfgram proteins (WP) and their relationship with
      2', 3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) in human, rat, sheep,
      bovine, guinea pig and chicken CNS myelin was investigated. Controlled digestion
      of myelin with trypsin gave a 35KDa protein band (WP-t) when electrophoresed on
      dodecyl sulfate-polyacrylamide gel in all species. Western blot analysis showed
      that the WP-t was derived from WP. WP-t was also formed when rat myelin was
      treated with other proteases such as kallikrein, thermolysin and leucine
      aminopeptidase. Staining for CNPase activity on nitrocellulose blots showed that
      WP-t is enzymatically active. Much of the CNPase activity remained with the
      membrane fraction even after treatment with high concentrations of trypsin when
      WP were completely hydrolysed and no protein bands with M.W > 14KDa were detected
      on the gels. Therefore protein fragments of WP with M.W < 14KDa may contain
      CNPase activity. From these results, it is suggested that the topological
      disposition of all the various WP is such that a 35KDa fragment is embedded in
      the lipid bilayer and the remaining fragment exposed at the intraperiod line in
      the myelin structure which may play a role in the initiation of myelinogenesis.

PMID- 7824063
TI  - Lack of effect of bilateral locus coeruleus lesion and antidepressant treatment
      on gamma-aminobutyric acidB receptors in the rat frontal cortex.
AB  - The aim of the present study was to investigate whether a disturbance of the
      central noradrenergic (NA) system could cause changes in gamma-aminobutyric acidB
      (GABAB) receptors in the rat frontal cortex. Manipulation of the NA projection to
      the frontal cortex was achieved by bilateral lesion of the locus coeruleus with 6
      hydroxydopamine (6-OHDA) or chronic treatment with the NA reuptake blocker and
      antidepressant drug, desipramine. Precautions were taken to ensure that the GABAB
      receptor assay was performed optimally and was not confounded by the presence of
      endogenously generated GABA. The results show conclusively that manipulation of
      the NA projection did not result in any significant change in the number (Bmax)
      or affinity (Kd) of GABAB receptors in the frontal cortex. These results do not
      support the hypothesis that hypoactivity of the central NA system can lead to
      changes in cortical GABAB receptors and that antidepressant drugs act by
      increasing GABAB receptor binding in the frontal cortex.

PMID- 7824064
TI  - Amino acid and purine release in rat brain following temporary middle cerebral
      artery occlusion.
AB  - Excitatory amino acid release and neurotoxicity in the ischemic brain may be
      reduced by endogenously released adenosine which can modulate both glutamate or
      aspartate release and depress neuronal excitability. The present study reports on
      the patterns of release of glutamate and aspartate; the inhibitory amino acids
      GABA and glycine; and of the purine catabolites adenosine and inosine from the
      rat parietal cerebral cortex during 20 and 60 min periods of middle cerebral
      artery (MCA) occlusion followed by reperfusion. Aspartate and glutamate efflux
      into cortical superfusates rose steadily during the period of ischemia and tended
      to increase even further during the subsequent 40 min of reperfusion. GABA
      release rose during ischemia and declined during reperfusion, whereas glycine
      efflux was relatively unchanged during both ischemia and reperfusion. Adenosine
      levels in cortical superfusates rose rapidly at the onset of ischemia and then
      declined even though MCA occlusion was continued. Recovery to pre-occlusion
      levels was rapid following reperfusion. Inosine efflux also increased rapidly,
      but its decline during reperfusion was slower than that of adenosine.

PMID- 7824065
TI  - Evidence of an oxidative challenge in the Alzheimer's brain.
AB  - Alzheimer's disease may arise from or produce oxidative damage in the brain. To
      assess the responses of the Alzheimer's brain to possible oxidative challenges,
      we assayed for glutathione, glucose-6-phosphate dehydrogenase, catalase and
      superoxide dismutase in twelve regions of Alzheimer's disease and aged control
      brains. In addition, we determined levels of malondialdehyde to evaluate lipid
      peroxidation in these brain regions. Most brain regions showed evidence of a
      response to an oxidative challenge, but the cellular response to this challenge
      differed among brain regions. These data suggest that the entire Alzheimer's
      brain may be subject to an oxidative challenge, but that some brain areas may be
      more vulnerable than others to the consequent neural damage that characterizes
      the disease.

PMID- 7824066
TI  - Alterations in monoamine levels in discrete regions of rat brain after chronic
      administration of carbamazepine.
AB  - Carbamazepine (25 mg/kg body weight) was administered intraperitoneally to adult
      male Wistar rats for 45 days and norepinephrine (NE), dopamine (DA) and serotonin
      (5-HT) levels were simultaneously assayed in discrete brain regions by high
      performance liquid chromatographic (HPLC) method. Experimental rats displayed no
      behavioral abnormalities. Body and brain weights were not significantly different
      from control group of rats. After exposure it was observed that norepinephrine
      levels were elevated in motor cortex (P < 0.01) and cerebellum (P < 0.05), while
      dopamine levels were decreased in these two regions (P < 0.001, P < 0.05).
      However, dopamine levels were increased in hippocampus (P < 0.01). Serotonin
      levels were significantly decreased in motor cortex (P < 0.001) and hypothalamus
      (P < 0.001) but increased in striatum-accumbens (P < 0.001) and brainstem (P <
      0.001). These results suggest that carbamazepine may mediate its anticonvulsant
      effect by differential alterations of monoamine levels in discrete brain regions
      particularly in motor cortex and cerebellum.

PMID- 7824067
TI  - Uptake of transmitter amino acids by glial plasmalemmal vesicles from different
      regions of rat central nervous system.
AB  - From rat hippocampal homogenate, we recently isolated a novel subcellular
      fraction richly containing glial plasmalemmal vesicles (GPV), which takes up
      glutamate remarkably as a synaptosomal fraction [Y. Nakamura et al. (1993) Glia,
      9, 48-56]. In the present study, we prepared GPV from different regions of rat
      CNS, namely olfactory bulb (Ob), cerebral cortex (Cx), caudatoputamen (Cp),
      hippocampus (Hp), cerebellum (Ce) and spinal cord (Sc), and analyzed their
      activities of Na(+)-dependent uptake of following neurotransmitters and a related
      compound; glutamate, gamma-aminobutyrate (GABA), glycine, dopamine and choline.
      The uptake activities of these amino acids were not significantly different
      between GPV and synaptosomes in each region. Regionally, however, the activities
      were varied considerably. The activities of glutamate uptake revealed in the
      following rank order: Cx, Hp, Cp > Ce, Ob > Sc. GABA uptake activities were: Ce >
      Ob, Cx, Hp > Cp, while glycine uptake activities were: Sc, Ce > Ob, Cp, Cx, Hp.
      On the other hand, the uptake activities of dopamine and choline were quite
      different between GPV and synaptosomes. Synaptosomal fraction from Cp took up
      dopamine in a high activity; however, GPV from the same tissue hardly showed the
      uptake activity. Choline was taken up by synaptosomes prepared from Hp but not by
      GPV.

PMID- 7824068
TI  - Compromised mitochondrial function results in dephosphorylation of tau through a
      calcium-dependent process in rat brain cerebral cortical slices.
AB  - Mitochondria play an important role in modulating intracellular levels of
      calcium, and therefore compromised mitochondrial function often leads to
      disruptions in calcium homeostasis. In this study, the effects of two uncouplers
      of oxidative phosphorylation, carbonyl cyanide-3-chlorophenylhydrazone (CCCP) and
      p-trifluoromethoxyphenylhydrazone (FCCP), on calcium-mediated modifications of
      the microtubule-associated protein, tau, in rat brain slices were examined.
      Incubation of slices with CCCP or FCCP resulted in an increase in electrophoretic
      mobility of several of the tau isoforms, with no apparent loss of intact tau or
      the appearance of degradation products. These data indicated that disrupting
      mitochondrial function by dissipating the transmembrane potential resulted in the
      dephosphorylation of tau. This finding was confirmed by using a front
      phosphorylation assay to demonstrate a CCCP-induced decrease in the
      phosphorylation state of tau. The dephosphorylation of tau induced by the proton
      ionophores appeared to be calcium-dependent since the effect was blocked by EGTA.
      In addition, the CCCP-induced dephosphorylation of tau was blocked by cyclosporin
      A, a selective inhibitor of the calcium-dependent phosphatase, calcineurin. These
      data strongly indicate that tau is a substrate for calcineurin in vivo. Finally,
      the levels of ATP were depleted to a similar extent in brain slices incubated in
      the presence of CCCP or CCCP and EGTA. These results demonstrated depletion of
      ATP alone was not sufficient to stimulate the dephosphorylation of tau in this
      experimental paradigm.

PMID- 7824069
TI  - Dihydrocodeinone-hydrazone, dihydrocodeinone-oxime, naloxone-3-OMe-oxime, and
      clocinnamox fail to irreversibly inhibit opioid kappa receptor binding.
AB  - Previous work from our lab identified two subtypes of the opioid kappa receptor.
      Whereas the kappa1 receptor can be labeled by [3H]U69,593 (5 alpha,7 alpha,8 beta
      (-)- N-methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro(4,5)dec-8-yl]-phenyl-
      benzeneacetamide), the kappa2 receptor can be labeled by [125I]OXY (6 beta
      125iodo-3,14-dihydroxy-17-cyclopropylmethyl-4,5 alpha-epoxymorphinan). Other data
      demonstrate that [125I]IOXY, like [3H]bremazocine, labels two populations of
      kappa2 receptors in guinea pig brain: kappa2a and kappa2b binding sites. In the
      present study, we tested the hypothesis that certain dihydrocodeinone and
      oxicodone derivatives, which have been shown to irreversibly block low affinity
      [3H]naloxone binding sites, would also bind irreversibly to opioid kappa receptor
      subtypes. We also tested the novel irreversible mu receptor antagonist,
      clocinnamox (14 beta-(p-chlorocinnamoylamino)-7,8-dihydro-N-cyclopropylmethylno
      rmorphinone mesylate). Wash-resistant inhibition (WRI) assays were conducted to
      detect apparent irreversible inhibition. The proportion of WRI attributable to
      inhibition of receptor binding, termed receptor inhibition (RI), was calculated
      by the equation: RI = WRI (wash-resistant inhibition) - SI (supernatant
      inhibition or inhibition attributable to residual drug.) Dihydrocodeinone
      hydrazone, dihydrocodeinone-oxime and naloxone-3-OMe-oxime failed to produce any
      wash-resistant inhibition of kappa receptor binding. In contrast, preincubating
      guinea pig membranes with 1 microM clocinnamox produced a substantial degree of
      wash-resistant inhibition (greater than 90%) at kappa1 and kappa2 binding sites.
      However, as indicated by supernatant inhibition values of 70% to 90%, there was a
      large amount of residual clocinnamox which remained despite the use of an
      extensive washing procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7824070
TI  - In vitro binding of [14C]2,5-hexanedione to rat neuronal cytoskeletal proteins.
AB  - 2,5-Hexanedione (2,5-HD) induces central-peripheral axonpathy characterized by
      the accumulation of 10-nm neurofilaments proximal to the nodes of Ranvier and a
      Wallerian-type degeneration. It has been postulated that neurofilament
      crosslinking may be involved in the production of this axonopathy. A potential
      initiating event in this neurotoxic process may be the direct binding of 2,5-HD
      to neurofilament and microtubule proteins. In this study, the in vitro binding of
      [14C]2,5-HD to neurofilament and microtubule proteins was examined. Neurofilament
      proteins isolated from rat spinal cord or microtubule proteins isolated from rat
      brain were incubated in the presence of 2,5-HD at concentrations ranging from 25
      to 500 mM. Quantitative analysis of sodium dodecyl sulfate (SDS) polyacrylamide
      gels revealed a dose- and time-dependent binding of 2,5-HD to both neurofilament
      proteins and microtubule proteins. Expressed as pmol 2,5-HD bound per microgram
      protein, the observed relative binding was MAP2 > NF160 > NF200 > > NF68 >
      tubulin. These data demonstrate the direct binding of 2,5-HD to cytoskeletal
      proteins including both neurofilaments and microtubules.

PMID- 7824071
TI  - Effect of phenylalanine and its metabolites on ATP diphosphohydrolase activity in
      synaptosomes from rat cerebral cortex.
AB  - The in vitro effects of phenylalanine and some of its metabolites on ATP
      diphosphohydrolase (apyrase, EC 3.6.1.5) activity in synaptosomes from rat
      cerebral cortex were investigated. The enzyme activity in synaptosomes from rats
      subjected to experimental hyperphenylalaninemia (alpha-methylphenylalanine plus
      phenylalanine) was also studied. In the in vitro studies, a biphasic effect of
      phenylalanine on both enzyme substrates (ATP and ADP) was observed, with maximal
      inhibition at 2.0 mM and maximal activation at 5.0 mM. Inhibition of the enzyme
      activity was not due to calcium chelation. Moreover, phenylpyruvate, when
      compared with phenylalanine showed opposite effects on the enzyme activity,
      suggesting that phenylalanine and phenylpyruvate bind to two different sites on
      the enzyme. The other tested phenylalanine metabolites phenyllactate,
      phenylacetate and phenylethylamine) had no effect on ATP diphosphohydrolase
      activity. In addition, we found that ATP diphosphohydrolase activity in
      synaptosomes from cerebral cortex of rats with chemically induced
      hyperphenylalaninemia was significantly enhanced by acute or chronic treatment.
      Since it is conceivable that ATPase-ADPase activities play an important role in
      neurotransmitter (ATP) metabolism, it is tempting to speculate that our results
      on the deleterious effects of phenylalanine and phenylpyruvate on ATP
      diphosphohydrolase activity may be related to the neurological dysfunction
      characteristics of naturally and chemically induced hyperphenylalaninemia.

PMID- 7824072
TI  - Effect of propylthiouracil-induced hypothyroidism on cerebral cortex of young and
      aged rats: lipid composition of synaptosomes, muscarinic receptor sites, and
      acetylcholinesterase activity.
AB  - The effect of hypothyroidism on the lipid composition of synaptosomes, density
      and affinity of muscarinic receptor sites, and acetylcholinesterase activity in
      the cerebral cortex of young and aged rats was investigated. The animals were
      made hypothyroid by adding 0.05% propyl-2-thiouracil to their drinking water for
      four weeks. This pathological state induced an increase in the relative
      percentage of sphingomyelin in young rats. In aged rats hypothyroidism induced a
      decrease of sphingomyelin and glycerophosphocholine and an increase of
      cholesterol. The effect of hypothyroid state on cerebral cortex resulted in an
      increase of acethylcholinesterase activity both in young and aged rats and was
      also reflected in an increase of density of M1-AChRs but only in the former.

PMID- 7824073
TI  - Inhibition by n-3 fatty acids of arachidonic acid metabolism in a primary culture
      of astroglial cells.
AB  - Docosahexaenoic acid (22:6 n-3) was present in low concentrations in a primary
      culture of rat brain astroglial cells, when compared to brain cortex. We have
      thus supplemented these cells with this fatty acid and investigated the effects
      of its incorporation in cell phospholipids on the conversion of arachidonic acid,
      20:4 n-6, through the cyclo and lipoxygenase pathways, after cell stimulation.
      Docosahexaenoic acid-enriched cells produced less thromboxane B2 and 6-keto
      Prostaglandin F1 alpha and markedly less 12-hydroxyeicosatetraenoic acid than
      unsupplemented cells, after stimulation with the Ca(2+)-ionophore A23187. The
      production of 15-hydroxyeicosatetraenoic acid from arachidonic acid was slightly
      increased in docosahexaenoic acid-supplemented cells. We have also supplemented
      these cells with eicosapentaenoic acid (20:5 n-3) and, in addition to
      accumulation of this fatty acid in cell phospholipids, we found elevation of 22:5
      n-3 and some increment of 22:6, confirming that glial cells are able to convert
      eicosapentaenoic acid to the long chain, more unsaturated derivatives. In
      conclusion, n-3 fatty acids, when supplemented to glial cells, appear to modulate
      the arachidonic acid cascade and to be converted through the elongation and
      desaturation pathways.

PMID- 7824074
TI  - Purification of brain microtubule-associated protein MAP1A.
AB  - Brain microtubule-associated protein MAP1A has been purified until homogeneity by
      using a novel procedure involving copolymerization with microtubules, treatment
      with poly-L-aspartic acid and FPLC. The purified protein retains its capacity to
      facilitate microtubule assembly.

PMID- 7824075
TI  - Inhibitory effects of calcium antagonists on mitochondrial swelling induced by
      lipid peroxidation or arachidonic acid in the rat brain in vitro.
AB  - Inhibitory effects of calcium antagonists, efonidipine (NZ-105), nicardipine,
      nifedipine, nimodipine and flunarizine, on mitochondrial swelling induced by
      lipid peroxidation or arachidonic acid in the rat brain in vitro were
      investigated. Mitochondrial swelling and lipid peroxidation induced by FeSO4 and
      ascorbic acid system showed a close and significant relationship. Mitochondrial
      swelling and lipid peroxidation induced by FeSO4 and ascorbic acid were inhibited
      by all of calcium antagonists tested. The order of inhibition was: flunarizine >
      nicardipine > efonidipine > nimodipine > nifedipine. This result suggests that
      calcium antagonists tested have anti-peroxidant activities resulting in
      protection of mitochondrial membrane damage and that each moiety of these
      structures would play an important role in appearance of anti-peroxidant
      activities. Furthermore, flunarizine and efonidipine inhibited mitochondrial
      swelling induced by arachidonic acid, which is not associated with lipid
      peroxidation. In contrast, nicardipine, nifedipine, and nimodipine did not
      inhibited this swelling. It is possible that flunarizine and efonidipine could
      directly interact with mitochondrial membrane. In conclusion, it is capable that
      calcium antagonists tested may protect from the membrane damage induced by lipid
      peroxidation and that flunarizine and efonidipine could stabilize the membrane,
      which is attributed to a direct interaction with the membrane.

PMID- 7824076
TI  - Muscarinic receptors binding in retinal pigment epithelium during rat
      development.
AB  - [3H]Quinuclidinyl benzylate (3H-QNB) specific binding of the developing rat
      retinal pigment epithelium (RPE) and neural retina has been examined. The binding
      of 3H-QNB to RPE was saturable and displaced by the antagonist pirenzepine.
      Scatchard analysis of 3H-QNB binding showed two high affinity sites to RPE, with
      KB = 2.6nM and 45 nM. Specific 3H-QNB binding membranes from neural retina
      exhibited a characteristic developmental profile. RPE showed a high density of 3H
      QNB binding sites through all developmental periods studied. The major onset of
      binding sites is at the time of RPE differentiation. Our data open the
      possibility of muscarinic receptors being involved in differentiation and/or
      proliferation of RPE.

PMID- 7824078
TI  - The effect of methyl palmoxirate on incorporation of [U-14C]palmitate into rat
      brain.
AB  - We examined the dose response, time course and reversibility of the effect of
      methyl 2-tetradecylglycidate (McN-3716, methyl palmoxirate or MEP), an inhibitor
      of beta-oxidation of fatty acids, on incorporation of radiolabeled palmitic acid
      ([U-14C]PA) from plasma into brain lipids of awake rats. MEP (0.1, 1 and 10
      mg/kg) or vehicle was administered intravenously from 10 min to 72 hr prior to
      infusion of [U-14C]PA. Two hr pretreatment with MEP (0.1 to 10 mg/kg) increased
      brain organic radioactivity 1.2 to 1.8 fold and decreased brain aqueous
      radioactivity by 1.2 to 3.0 fold when compared to control values. At 10 mg/kg,
      MEP significantly increased brain organic fraction from 40% in controls to 85%,
      30 min to 6 hr pretreatment, and resulted in a redistribution of the radiolabeled
      fatty acid toward triacylglycerol. MEP changed the lipid/aqueous brain ratio of
      incorporated [U-14C]PA from 0.67 to 5.7. The incorporation rate coefficient, k*,
      was significantly increased by MEP (10 mg/kg) at 2 hr (31%), 4 hr (59%) and 6 hr
      (34%). All effects were reversed by 72 hr, consistent with a half-life of
      approximately 2 days for carnitine palmitoyl transferase I. These results
      indicate that intravenous MEP may be used with [1-11C]palmitic acid for studying
      brain lipid metabolism in vivo by positron emission tomography, as it
      significantly reduces the large unincorporated aqueous fraction that would result
      in high background radioactivity.

PMID- 7824077
TI  - Presynaptic modulation by eicosanoids in cortical synaptosomes.
AB  - In continuing experiments to determine the ionic basis of inhibitory presynaptic
      modulation, rat cortical synaptosomes were employed and receptor-activated K+
      efflux was determined with a K+ sensitive electrode. When synaptosomes were sub
      optimally depolarized by veratridine, the addition of agents that activated
      purinergic, alpha 2-adrenergic, muscarinic and opioid receptors all promoted K+
      efflux. With 2-chloroadenosine as a model inhibitory presynaptic modulator, the
      increased K+ efflux evoked by this agent was blocked by the cyclooxygenase
      inhibitor indomethacin suggesting that arachidonic acid or its metabolites was an
      intermediary in opening the channel. When arachidonic acid and PGE2 were tested,
      both promoted K+ efflux that was inhibited by dendrotoxin and mast cell
      degranulating peptide, two agents that are known to inhibit a delayed rectifier
      K+ current. Our results suggest that via eicosanoid second messengers, inhibitory
      presynaptic modulators open a sub-class of K channels that hyperpolarize nerve
      terminals, therefore less Ca2+ would enter per nerve impulse and thus the evoked
      release of neurotransmitters would be decreased.

PMID- 7824079
TI  - Modulation of arginine vasopressin secretion from cultured ovine hypothalamic
      cells by glucocorticoids and opioid peptides.
AB  - In sheep, arginine vasopressin (AVP) appears to be a more potent ACTH-releasing
      factor than ovine corticotrophin-releasing hormone. In order to investigate the
      neuroendocrine regulation of AVP secretion we have developed a novel system for
      maintaining fetal ovine hypothalamic neurones in serum-free culture. Hypothalamic
      neurones derived from fetal sheep at day 70 gestation (term = 145 days) secreted
      AVP under basal conditions and in response to repeated potassium-induced
      depolarizations, for up to 35 days in vitro. AVP secretion was time- and calcium
      dependent. AVP secreted from ovine hypothalamic cells co-eluted with synthetic
      AVP on a Sephadex chromatography column and diluted in parallel with AVP standard
      in the radioimmunoassay. The addition of cortisol (150 nM) to medium bathing
      ovine hypothalamic cells significantly inhibited basal, and potassium-induced AVP
      secretion without altering the AVP content of the cell cultures. Furthermore, the
      opioid peptide [D-Pro10]Dynorphin(1-11) which acts via the kappa opioid receptor,
      significantly inhibited basal and potassium-stimulated AVP secretion, an effect
      which was abolished when cells were cultured in the presence of cortisol. These
      data show that hypothalamic AVP is a site for negative feedback regulation within
      the ovine hypothalamic-pituitary-adrenal axis. Furthermore, these data suggest
      that the kappa opioid system inhibits AVP secretion from ovine hypothalamic
      neurones, a response which is modulated by glucocorticoids.

PMID- 7824080
TI  - Calcium influx through neuronal-type nicotinic acetylcholine receptors present on
      the neuroendocrine cells of the porcine pars intermedia.
AB  - The properties of neuronal-type nicotinic acetylcholine receptors (nAChRs)
      present on the neuroendocrine cells of the porcine pars intermedia of the
      pituitary were studied in intact single cell using measurements of the free
      intracellular Ca2+ concentration ([Ca]i) with the calcium-sensitive dye fura 2.
      Local application of an extracellular solution containing 50 mM K+ or of the
      selective nAChR agonist, 1,1-dimethyl-4-phenylpiperazinium (DMPP) depolarised the
      cells and induced an elevation in [Ca]i. The effect of DMPP on [Ca]i was dose
      dependent (EC50 = 6 microM), reversibly blocked by d-tubocurarine and strictly
      dependent on the concentration of extracellular Ca2+. The calcium channel blocker
      Cd2+ (100 microM) reversibly blocked 80% of the response induced by 50 mM K+,
      whereas it reduced the DMPP response by only 50%. In the absence of extracellular
      Na+, DMPP no longer depolarised the cells but still increased [Ca]i. The rise in
      [Ca]i under these conditions represented 41% of the control response, i.e. in the
      presence of external Na+. Thus activation of nAChRs induced an elevation in [Ca]i
      which was in part independent of cell depolarisation. This was confirmed by
      recording simultaneously, under whole-cell voltage-clamp, a rise in [Ca]i
      associated with the inward nicotinic current. During prolonged application of the
      agonist (50 s), the amplitude of the nicotinic current decayed rapidly to a very
      low plateau level reflecting nAChR desensitisation. However, photometric
      experiments performed on intact non-dialysed cells revealed the presence of a
      slowly decaying phase in [Ca]i throughout the application of DMPP. This suggests
      the persistence of a substantial Ca2+ influx during prolonged exposure to the
      agonist. Taken together, our results show that stimulation of nAChRs induces an
      influx of Ca2+ which elevates [Ca]i. This phenomenon is due to activation of
      voltage-dependent Ca2+ channels and to Ca2+ entry through the nAChR.

PMID- 7824081
TI  - Short applications of gamma-aminobutyric acid increase intracellular calcium
      concentrations in single identified rat lactotrophs.
AB  - We have investigated the direct effect of GABA receptor agonists on the cytosolic
      free calcium concentration ([Ca2+]i) and the membrane potential of rat
      lactotrophs in primary culture. [Ca2+]i was recorded in single identified
      lactotrophs by dual emission microspectrofluorimetry using indo-1 as
      intracellular fluorescent calcium probe. Whole cell and perforated patch-clamp
      were performed. A short application of GABA (10(-5) M, 10 s) induced a marked
      transient [Ca2+]i increase in 66% of lactotrophs, which could be readily mimicked
      by muscimol (10(-5) M). By contrast, neither L-homocarnosine (10(-3) M) nor
      baclofen (10(-5) M), a GABAB agonist, had any effect on [Ca2+]i. The GABA-induced
      [Ca2+]i increase was antagonized by picrotoxin (10(-5) M), bicuculline methiodide
      (10(-5) M) and strychnine (10(-4) M), demonstrating GABAA receptor specificity.
      Furthermore, clonazepan (1.5 x 10(-4) M) could potentiate the GABA effect on
      [Ca2+]i. The [Ca2+]i increase disappeared in the absence of Ca2+ in the
      extracellular medium or in the presence of Ca2+ channel blockers (cadmium, PN 200
      110). GABA and muscimol depolarized the membrane potential with a concomitant
      fall in cell input resistance, thus suggesting, as in other cell types, the
      opening of receptor-operated chloride channels. When Ca2+ entry was prevented by
      the use of cadmium (500 x 10(-6) M), GABA still elicited membrane depolarization
      but did not raise [Ca2+]i. Our results suggest that a short application of GABA
      leads to Ca2+ entry through voltage-gated Ca2+ channels in single lactotrophs.
      This Ca2+ influx is due to depolarization of the prolactin cell.

PMID- 7824082
TI  - Selective effect of a diet-induced decrease in the arachidonic acid membrane
      phospholipid content on in vitro phospholipase C and adenylate cyclase-mediated
      pituitary response to angiotensin II.
AB  - Young rats were fed on an essential fatty acid (EFA)-deprived diet for 6 weeks
      after weaning. Their pituitary was removed and adenohypophyseal cells dispersed
      and maintained in culture. Membrane lipids were analyzed and basal and stimulated
      levels of hormone secretion were measured after 4-day incubation in a culture
      medium containing or not 160 microM arachidonic acid 20:4n-6 (AA) in order to
      obtain EFA-deficient or EFA-restored pituitary cells, respectively. In EFA
      deficient cells membrane phosphoglycerides (PGL) were depleted in AA and adrenic
      acid 22:4n-6; the deficit was overcome by incubation in the presence of AA.
      Depletion diversely affected PGL classes. AA was highly depleted in choline
      phosphoglycerides (ChoPG), only moderately depleted in serine and ethanolamine
      phosphoglycerides (SerPG and EtnPG) and not depleted at all in inositol
      phosphoglycerides, suggesting preferential preservation of AA in that class of
      PGL. Restoration of AA by addition of the fatty acid to the culture medium was
      complete for ChoPG and EtnPG and only partial for SerPG. Depressed levels of AA
      and adrenic acid in PGL were compensated for by a concomitant increase in 20:3n-9
      and 22:3n-9. Growth hormone and prolactin (PRL) secretion was assessed by
      radioimmunoassay and possible effects of a membrane AA deficit on hormone
      regulation were tested in cells challenged by either growth hormone-releasing
      hormone, thyrotropin-releasing hormone, angiotensin II (AII), vasoactive
      intestinal peptide (VIP) or dopamine. Neither basal nor stimulated growth hormone
      secretion was different from controls in EFA-deficient cells. PRL modulation by
      VIP or dopamine was not affected either in EFA-deficient cells. In contrast, the
      capacity of AII, but not of thyrotropin-releasing hormone, to release PRL was
      markedly decreased in EFA-deprived cells. It was restored by addition of AA to
      the incubation medium. Parallel depression of AII-induced inositol phosphates and
      cAMP accumulation was also observed after EFA deficiency. When tested on
      membranes, the paradoxical inhibition of adenylate cyclase by AII documented by
      previous observations was reinforced in EFA-deficient membranes. In contrast,
      binding of AII was not affected by EFA deficiency. It is concluded that under our
      experimental conditions EFA deficiency affects selectively coupling of the AII
      receptor to its effectors without alteration of binding. The effect could involve
      changes in receptor interactions with coupling proteins.

PMID- 7824083
TI  - Systemically administered histamine H1 and H2 receptor antagonists do not block
      the ACTH response to bacterial lipopolysaccharide and interleukin-1.
AB  - The administration of lipopolysaccharide (LPS) results in the activation of the
      hypothalamic-pituitary-adrenal axis (HPAA). We recently reported that the
      participation and interaction of LPS-induced proinflammatory cytokines were
      obligatory for the stimulation of adrenocorticotropic hormone (ACTH) release by
      LPS. LPS and LPS-derived cytokines also stimulate the release of histamine (HA).
      HA is a known hypothalamic neurotransmitter and activates the HPAA. Therefore, to
      elucidate the role of HA in LPS- and cytokine-induced ACTH release, we evaluated
      the effects of several HA H1 and H2 receptor antagonists on the ACTH response to
      LPS, recombinant human interleukin-1 alpha (rhIL-1 alpha) and HA in mice.
      Although all 3 of the H1 receptor antagonists administered (mepyramine (MEP),
      diphenhydramine (DPH) or promethazine (PMZ) were able to block the 10-min ACTH
      response to HA, only PMZ (a less selective H1 receptor antagonist than MEP) was
      able to reduce the LPS- or rhIL-1 alpha-induced ACTH responses. Ranitidine, a
      powerful and selective H2 receptor antagonist, had little effect on the LPS- and
      rhIL-1 alpha-induced ACTH responses, while metiamide (MET), a much less potent
      first-generation H2 receptor antagonist, substantially diminished ACTH release.
      The greater effectiveness of PMZ, in contrast to MEP or DPH, probably relates to
      the ability of phenothiazine derivatives to inhibit non-HA-dependent pathways
      involved in the stimulation of the HPAA by cytokines; the same may be true of
      MET.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7824084
TI  - Prostaglandins mediate the ACTH response to interleukin-1-beta instilled into the
      hypothalamic median eminence.
AB  - Interleukin-1 beta (IL-1 beta) is a potent ACTH secretagogue which activates the
      release of hypothalamic CRH. Direct injections of IL-1 beta into the hypothalamic
      median eminence (ME), a site which lacks a blood-brain barrier, has been shown to
      rapidly induce ACTH secretion. Therefore, the ME is a likely site whereby
      circulating IL-1 beta can access the brain to stimulate CRH and, consequently,
      ACTH secretion. To further evaluate this hypothesis, an angular stereotaxic
      approach was developed to localize the spread of IL-1 beta to the ME and to
      optimally separate the injectate from the hypothalamic paraventricular nucleus
      (PVN), another proposed site of IL-1 action. Studies of the diffusion of [125I]
      IL beta (100 nl delivered over 60 s) showed that 97% remained within 200 microns
      of the ventral surface of the hypothalamus and 87% was contained within a radius
      of 550 microns of the injection site in the sagittal plane. Additional rats
      received recombinant human IL-1 beta (0.2-25.0 ng in 100 nl) into the ME (intra
      ME). Plasma ACTH levels were significantly elevated by a much lower dose (0.5 ng,
      p < 0.001) of IL-1 beta than that previously reported. Responses appeared to be
      dose-dependent and ACTH was maximally stimulated by 2.0 ng IL-1 beta. Also,
      immunocytochemically labelled CRH in the ME was markedly depleted after intra-ME
      IL-1 beta. Indomethacin, an inhibitor of prostaglandin (PG) synthesis, has been
      shown to block both the induction of CRH secretion by IL-1 beta from hypothalamic
      explants, as well as the ACTH response to intravenous IL-1 beta. Thus,
      indomethacin was used to determine whether PGs are mediators of the ACTH response
      to IL-1 beta delivered into the ME. The ACTH response was abolished (p < 0.005)
      when a low dose of indomethacin (1 mg/kg i.v.) was administered 20 min before
      intra-ME IL-1 beta (25 ng). Finally, plasma ACTH was elevated in a dose-dependent
      manner by the intra-ME administration of PGs. The hierarchy of ACTH responses to
      PGE2 were: CSF < 0.5 micrograms (p < 0.001) = 2.0 micrograms < 4.0 micrograms (p
      < 0.05). Responses to PGF2 alpha were: CSF < 0.5 micrograms (p < 0.001) < 2.0
      micrograms (p < 0.05) = 4.0 micrograms. Since these PGs appear to activate
      different second-messenger systems, a submaximal dose of each was administered
      alone or in combination.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7824085
TI  - Increased numbers of corticotropin-releasing hormone expressing neurons in the
      hypothalamic paraventricular nucleus of depressed patients.
AB  - The hypothalamo-pituitary-adrenal (HPA) axis is known to be activated in
      depressed patients. Although direct evidence is lacking, this activation is
      hypothesized to be due to hyperactivity of corticotropin-releasing hormone (CRH)
      neurons of the hypothalamic paraventricular nucleus (PVN). Recent
      immunocytochemical studies in experimental animals and in humans showed that the
      number of CRH-expressing neurons correlated with the activity of these neurons.
      In addition, colocalization of AVP in CRH neurons has been shown to be an index
      for the secretory activity. Therefore, we estimated the total number of CRH
      immunoreactive neurons and their fraction showing colocalization with AVP in the
      PVN of 10 control subjects and of 6 depressed patients who were diagnosed to be
      suffering from a major depression or a bipolar disorder. The mean total number of
      CRH-expressing neurons of the 6 depressed patients was four times higher, and the
      number of CRH neurons co-expressing AVP was almost three times higher than those
      in the control group. We also determined the two activity parameters of CRH
      neurons in the PVN of 2 subjects with a depressive organic mood syndrome or a
      depressive disorder not otherwise specified. In these two 'non-major depressed'
      subjects, the activity parameters of CRH neurons were comparable to those of
      control subjects. Our observations strongly support the hypothesis that CRH
      neurons in the PVN are hyperactivated in major depressed patients. This
      hyperactivity might be causally related to at least part of the symptomatology of
      depression.

PMID- 7824086
TI  - Characterization of 17 beta-hydroxysteroid dehydrogenase activity and mRNA
      abundance in human meningioma tumors.
AB  - Meningioma benign tumors possess significant levels of 17 beta-hydroxysteroid
      dehydrogenase (17 beta-HSD) activity. Two different 17 beta-HSDs have been cloned
      and characterized. The cytosolic 17 beta-HSD I which exclusively catalyzes the
      interconversion of 17 beta-estradiol (E2) and estrone (E1) preferentially uses
      NADP+ and NADPH as cofactors. In contrast, the mitochondrial-microsomal 17 beta
      HSD II catalyzes both the estrogenic as well as the androgenic substrates of the
      17 beta-HSD and uses NAD+ and NADH as cofactors. We demonstrated here that the 17
      beta-HSD activity in meningioma tissue homogenate is both estrogenic and
      androgenic with Km values of 2.4, 0.4, 14.7, and 2.0 microM for E2, E1,
      testosterone (T), and delta 4-androstenedione (delta 4), respectively. NAD(+)
      NADH is almost exclusively used as cofactor in this tissue. Moreover,
      fractionation of meningioma tissue revealed that most of the 17 beta-HSD activity
      is present in the mitochondrial-microsomal fraction. Although Northern blot
      analysis on meningiomas with a specific probe for human 17 beta-HSD I showed no
      band, the specific cDNA probe of human 17 beta-HSD II hybridized at the expected
      size of 1.5 kb, which was also present in placenta. On four different meningioma
      tumors, we were able to correlate 17 beta-HSD II mRNA expression to high levels
      of 17 beta-HSD activity. Taken together, the present data suggest that the
      meningioma 17 beta-HSD could be the 17 beta-HSD II.

PMID- 7824087
TI  - Effect of erythromycin on pancreatic polypeptide release: role of the vagal
      nerve.
AB  - To determine whether long vagal cholinergic pathways are involved in erythromycin
      induced pancreatic polypeptide release, erythromycin was administered as an
      intravenous bolus injection to 9 healthy volunteers (group A) and to 13 patients
      (group B) with impaired vagal function as a result of truncal vagotomy or
      accidental vagotomy after antireflux surgery. In 7 of these patients (group B1)
      an antrectomy was also performed, while in the other 6 patients (group B2) the
      antrum was not removed. Pancreatic polypeptide was measured by radioimmunoassay
      at 5-min intervals twice before and at 2, 5, 10, 15, 30, 45 and 60 min after a
      3.5 mg/kg bolus injection of erythromycin. On another day, a standard meal was
      administered and plasma pancreatic polypeptide was measured at 10-min intervals
      for 1 h. Erythromycin injection resulted in a lower integrated pancreatic
      polypeptide response in the patients of group B1 (247 +/- 89 pmol/l x 15 min; p =
      0.005) and group B2 (497 +/- 111 pmol/l x 15 min; p = 0.05) when compared to the
      healthy subjects of group A (1,136 +/- 227 pmol/l x 15 min). The pancreatic
      polypeptide response to erythromycin in group B1 was reduced when compared to
      group B2, but the difference just failed to reach statistical significance (0.05
      < p < 0.10). In the first 30 min after ingestion of a meal (cephalic phase)
      pancreatic polypeptide release was also markedly lower in group B1 (1,461 +/- 304
      pmol/l x 30 min; p < 0.005) and group B2 (1,452 +/- 215 pmol/l x 30 min; p <
      0.005) when compared to group A (3,541 +/- 452 pmol/l x 30 min).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7824088
TI  - Early detection of cerebral infarction and hypoxic ischemic encephalopathy in
      neonates using diffusion-weighted magnetic resonance imaging.
AB  - Twelve newborn infants with clinical evidence of hypoxic ischemic brain injury
      had conventional and diffusion-weighted magnetic resonance imaging (MRI)
      performed one to six (median two) days and 7-42 days after birth. The extent and
      conspicuity of the early abnormalities was greater with diffusion-weighted than
      with conventional imaging in each of the four infants with neonatal infarction
      and in four of the infants with Grades II or III hypoxic ischemic encephalopathy
      (HIE). No abnormality was seen with either technique in the other four infants
      who had Grades I or II HIE. Diffusion weighted MRI may be important for the early
      diagnosis and grading of infants with hypoxic ischemic brain injury.

PMID- 7824090
TI  - Primary degeneration of the granular layer of the cerebellum. A study of 14
      patients and review of the literature.
AB  - Primary degeneration of the granular layer of the cerebellum is an autosomal
      recessive disorder exhibiting characteristic clinical features: hypotonia,
      strabismus, delayed motor development, nonprogressive ataxia, delayed language
      development with dysarthria and mental retardation. We studied fourteen children,
      seven of each gender. Neuroimaging tests including pneumoencephalography,
      computed tomography (CT) and magnetic resonance imaging (MRI) showed severe
      cerebellar atrophy in all. MRI best demonstrated the cerebellar lesion, revealing
      great uniformity amongst the cases. Vertebrobasilar angiography was performed in
      two cases and showed marked hypoplasia of the cerebellar arteries, predominantly
      the posterior inferior cerebellar artery (PICA) and its branches. Necropsy was
      performed in three cases; cerebellar atrophy with loss of granular cells and
      diverse abnormalities of the Purkinje cells was found in two. The third, the
      sister of one of the other two cases, had a similar but shorter clinical course
      and died at three months of age. Her sister, who died at 5 years of age,
      presented a severe cerebellar atrophy with typical changes in the granular cell
      layer and Purkinje cells. In the third patient, who lived three months, only
      focal cerebellar folial atrophy with no microscopic changes in the granular cell
      layers was present. Though this case cannot objectively be included in the
      cerebellar atrophy syndrome with granular cell loss, her family history and
      clinical picture suggest the same disease. The findings observed in our series
      and the study of cases described in the literature, suggest that there are
      several forms of this disease which differ mainly in severity and neurological
      evolution. The cerebellar lesion seems to be a progressive atrophic process with
      the most severe changes during the early years of life.

PMID- 7824089
TI  - Coisogenic all-plus-one immunization: a model for identifying missing proteins in
      null-mutant conditions. Antibodies to dystrophin in mdx mouse after
      transplantation of muscle from normal coisogenic donor.
AB  - Specific antibody response against an alien protein is one of the basic
      immunologic mechanisms in immunecompetent organisms. They can be used as a first
      step in various approaches leading to the identification of proteins or even an
      antigen-encoding gene. Accordingly, we wanted to find out whether a null-mutant
      immunecompetent organism would produce specific antibodies against the missing
      gene product. We chose the mouse mutant mdx (X-linked muscular dystrophy) which
      represents a null-mutant condition for the gene product of the Duchenne muscular
      dystrophy (DMD) gene, dystrophin. When dystrophin-deficient mdx mice received
      dystrophin-containing muscle grafts from coisogenic normal mice, high titres of
      antibodies specific for dystrophin were detected in the transplanted animals'
      sera. Because dystrophin-containing muscle grafts were not rejected but have
      properly regenerated even in the presence of high titre antibodies against
      dystrophin, these findings have important bearings on all therapeutical
      strategies based on dystrophin supplementation. Using the mdx mouse as null
      mutant model we showed that there was no immune tolerance for the missing protein
      but specific antibodies were produced when the organism came in contact with this
      protein. This simple approach may serve as a shortcut for identifying missing
      proteins presumably not only in neuromuscular disorders but in a wide range of
      diseases where null-mutant animal models and corresponding coisogenic inbred
      strains exist.

PMID- 7824091
TI  - Prognostic value of early MR imaging in term infants with severe perinatal
      asphyxia.
AB  - The prognostic significance of magnetic resonance imaging (MRI) in the neonatal
      period was studied prospectively in 43 term infants with perinatal asphyxia. MRI
      was performed between 1 and 14 days after birth with a high field system (2.35
      Tesla). Neurodevelopmental outcome was assessed by a standardized neurological
      examination and the Griffiths developmental test at a mean age of 18.9 months.
      The predictive value of the various MRI patterns was as follows: Severe diffuse
      brain injury (pattern AII+III; n = 7) and lesions of thalamus and basal ganglia
      (pattern C; n = 5) were strongly associated with poor outcome and greatly reduced
      head growth. Mild diffuse brain injury (pattern AI; n = 7), parasagittal lesions
      (B; n = 7), periventricular hyperintensity (D; n = 2), focal brain necrosis and
      hemorrhage (E; n = 3) and periventricular hypointense stripes (on T2-weighted
      images; F; n = 3) led in one third of the infants to minor neurological
      disturbances and mild developmental delay. Infants with normal MRI findings (G; n
      = 9) developed normally with the exception of one infant who was mildly delayed
      at 18 months. The results indicate that MRI examination during the first two
      weeks of life is of prognostic significance in term infants suffering from
      perinatal asphyxia. Severe hypoxic-ischemic brain lesions were associated highly
      significantly with poor neuro-developmental outcome, whereas infants with
      inconspicuous MRI developed normally.

PMID- 7824092
TI  - Evolution of early hemiplegic signs in full-term infants with unilateral brain
      lesions in the neonatal period: a prospective study.
AB  - Neonates with unilateral hemispheric lesions detected by imaging in the newborn
      period are at risk for developing hemiplegia. Five full-term infants with
      predominantly unilateral lesions identified by cranial ultrasound in the neonatal
      period and confirmed with MRI were examined clinically at regular intervals in
      order to establish the development, incidence and evolution of later hemiplegia
      and the evolution of hemiplegic signs. In the neonatal period the infants had
      either a normal examination or subtle transient abnormalities. Abnormalities were
      not seen until 6 months of age in infants who developed hemiplegia. The number of
      hemiplegic signs in each child increased with time, the earlier the signs
      appeared the more severe the hemiplegia. In some infants deterioration with loss
      of preexisting skills was observed. At 24 months two of the infants were normal,
      one had a mild and two a moderate hemiplegia.

PMID- 7824093
TI  - Neonatal cerebral circulation in relation to neurosonography and neurological
      outcome: a pulsed Doppler study.
AB  - In the pathogenesis of neonatal intracranial pathology and adverse neurologic
      outcome, severe instability of the neonatal cerebral circulation might play an
      important role. To examine this hypothesis the relationship was explored between
      intracranial pathology as detected by neurosonography during the first week of
      life, changes in cerebral blood flow velocity (CBFV) as measured by Doppler
      ultrasound in the same period and neurologic outcome, as measured by standardized
      tests during the first year of life. A group of 128 infants born after a
      pregnancy duration between 25 2/7 and 32 6/7 weeks was studied. In 40% of the
      infants, the time of occurrence of both types of intracranial pathology was
      within 1 hour after birth. No relation could be demonstrated between this
      occurrence and CBFV. Also after the appearance of intracranial pathology no
      specific changes in CBFV were seen. CBFV was associated with neurological outcome
      at term age. However, CBFV did not predict outcome of neurological examination at
      6 and 12 months of corrected age. Intracranial hemorrhages were associated with
      abnormal neurological outcome at all assessments. Ischemic lesions were only
      associated with adverse outcome at 12 months of age.

PMID- 7824094
TI  - The metabolization of carbamazepine to CBZ-10,11-epoxide in children from the
      newborn age to adolescence.
AB  - CBZ-10,11-epoxide is a major metabolite of CBZ. It has anticonvulsive properties
      and may be responsible for side-effects of CBZ treatment. Fifty-two children
      between the age of 2 weeks and 15 years were treated with CBZ (mean dosage 17
      mg/kg body weight) either as mono- (n = 36) or in polytherapy (n = 16). The drug
      was delivered as an oral solution, as a nonretarded tablet or, most frequently,
      as a retarded tablet. The duration of treatment ranged from 1 to 94 months with
      23 patients being on treatment for less than 3 months. Blood samples were taken
      with random timing after the last ingestion of the drug. The relative
      concentration of CBZ epoxide (expressed in % of CBZ) was higher in infants
      (median 48.9%) than in older children (median 14.9% in the 12-15-year-old group).
      A significant linear correlation with age was found (p < 0.001). In addition to
      young age, polytherapy (p < 0.01) and administration as a nonretarded formulation
      rather than as a retarded tablet (p < 0.05) induced a higher relative
      concentration of the epoxide. The relative concentration of the epoxide did not
      correlate with the serum CBZ concentration and the duration of treatment.
      Although in our study high epoxide levels were not related to clinical side
      effects, we recommend that in very young children polytherapy treatment with
      carbamazepine should be performed with caution and in difficult cases a
      determination of the epoxide level should be considered.

PMID- 7824095
TI  - Selenium deficiency triggering intractable seizures.
AB  - Two children with severe neurodevelopmental retardation and elevated liver
      function tests developed intractable seizures during the first year of life.
      Detectable neurometabolic conditions have been ruled out. At the time of seizures
      evidence for systemic selenium deficiency could be documented. The youngest
      patient, who manifested intractable fits from the fourth day of life, died at the
      age of ten months. Neuropathologic examination was consistent with Progressive
      Neuronal Degeneration of Childhood (PNDC) with liver disease or formerly known as
      Alpers disease. In the oldest child, whose diet was normally balanced, fits
      started from the age of 11 months and features of long-standing selenium
      deficiency became apparent from the age of 1 1/2 years and consisted of liver
      function disturbances, depigmented hair and osteoarthropathy. Oral substitution
      with selenium supplements in both children (3-5 micrograms/kg body weight)
      resulted in reduction of seizures and improvement of the EEG recordings after two
      weeks while liver function became normal. Two of the seleno-dependent enzymes
      Glutathione Peroxidase (GPX) and Phospholipid Hydroperoxide Glutathione
      Peroxidase (PHGPX) are speculated to play a key-role in the defence of neuronal
      cells against oxygen radical formation and peroxidative processes. Our findings
      support the hypothesis that the presence of selenium depletion in the brain
      amongst patients with epilepsy constitutes an important triggering factor for the
      origin of intractable seizures and subsequent neuronal damage.

PMID- 7824096
TI  - Autosomal dominant cerebellar phenotypes: the genotype has settled the issue.

PMID- 7824097
TI  - Reversible MRI abnormalities following seizures.
AB  - We describe eight patients with reversible MRI changes following seizures. The
      patients were mostly young with a serious underlying medical problem; MRI
      abnormalities were localized primarily in the posterior vascular boundary zones.
      A likely mechanism for these lesions is edema secondary to disruption in the
      blood-brain barrier. Recognition of the transient radiologic changes may aid in
      the diagnostic and therapeutic management of seizures.

PMID- 7824098
TI  - Chronic encephalitis and epilepsy (Rasmussen's encephalitis): detection of
      cytomegalovirus and herpes simplex virus 1 by the polymerase chain reaction and
      in situ hybridization.
AB  - We made a pathologic diagnosis of chronic encephalitis on surgical resections or
      autopsy material in 10 patients with intractable seizures and studied the
      specimens by immunohistochemistry for herpes simplex virus (HSV) 1 and 2 and
      cytomegalovirus (CMV) as well as by the polymerase chain reaction (PCR) for viral
      DNA sequences (HSV1, HSV2, and CMV). We also assessed eight patients
      (nonepileptic) with pathologically documented or clinically suspected
      encephalitis and five resections from epileptics without encephalitis.
      Immunohistochemistry for viral antigens was negative in all cases. Using PCR
      assay, CMV was present in six and HSV1 in two of 10 epilepsy patients with
      chronic encephalitis. We demonstrated CMV by in situ hybridization in two of the
      six patients positive for CMV by PCR. We found no viral sequences by PCR in five
      epileptics without encephalitis. Of the eight patients (nonepileptic) with
      clinically suspected or pathologically confirmed encephalitis, two cases showed
      CMV sequences by PCR. These observations suggest that PCR allows detection of
      viral sequences in some cases of chronic encephalitis associated with epilepsy
      that may be missed by in situ hybridization.

PMID- 7824099
TI  - Adenosine triphosphate deficiency: a genre of optic neuropathy.
AB  - PURPOSE: To offer clinical evidence that deficiency of vitamin B12 may adversely
      affect the neuronal function of patients who also have the 14,484 mitochondrial
      DNA mutation associated with Leber's hereditary optic neuropathy (LHON). METHODS:
      A case of a 27-year-old man with vitamin B12 deficiency and the 14,484
      mitochondrial DNA mutation is presented and the literature on causes of some
      metabolic optic neuropathies reviewed. RESULTS: Visual loss and neurologic
      symptoms of vitamin B12 deficiency occurred together, at a time when the level of
      vitamin B12 was subnormal. Vision and other sensory functions began to improve
      within 2 months of vitamin therapy, and normal vision eventually was restored.
      CONCLUSIONS: The relatively prompt improvement and the eventual complete recovery
      of vision following vitamin replacement therapy suggest that the subnormal level
      of vitamin B12 precipitated visual loss. Given the clinical similarities of
      subnormal vitamin B12, LHON, and nutritional/tobacco amblyopia, deficiency of
      adenosine triphosphate might be a unifying etiology for several types of optic
      neuropathy. This energy hypothesis provides a theoretical basis for the enigmatic
      phenomena of centrocecal scotomata and recovery of visual function after
      prolonged blindness.

PMID- 7824100
TI  - Propagation of interictal epileptic activity in temporal lobe epilepsy.
AB  - We recorded interictal spikes with closely spaced scalp electrodes and sphenoidal
      electrodes in four patients with temporal lobe epilepsy. We used multiple dipole
      modeling to study the number, three-dimensional intracerebral location, time
      activity, and functional relationship of the neuronal sources underlying the
      epileptic spike complexes. In all patients, we found two significant sources
      generating the interictal spikes which showed considerable overlap in both space
      and time. Source 1 was located in the mesiobasal temporal lobe and generated a
      restricted negativity at the ipsilateral sphenoidal electrode and a widespread
      positivity over the vertex. Source 2 could be attributed to the lateral temporal
      neocortex and was associated with a relatively restricted negativity at the
      ipsilateral temporal electrodes and a more widespread positivity over the
      contralateral hemisphere. The sources were well separated in space, with an
      average distance of 45 mm between them. The time activities of both sources
      showed similar biphasic patterns, with the mesial source leading the lateral
      source by approximately 40 msec, suggesting propagation of interictal epileptic
      activity from the mesiobasal to the lateral temporal lobe.

PMID- 7824101
TI  - FDG-PET and volumetric MRI in the evaluation of patients with partial epilepsy.
AB  - We performed interictal FDG-PET- and MRI-based hippocampal volumetric
      measurements on 18 adult patients with complex partial epilepsy of temporal lobe
      origin in whom we had identified their ictal focus by video-telemetry EEG.
      Sixteen patients (89%) had regional hypometabolism, 11 (61%) had focal 1.5-tesla
      T2-weighted MRI (two structural abnormalities, nine hippocampal formation [HF]
      increased T2 signal), and nine (50%) had absolute HF atrophy ipsilateral to the
      temporal ictal focus. Ten (55%) had abnormal L/R HF ratios, nine ipsilateral to
      the EEG focus. All patients with abnormal MRI volumetric studies had focal PET
      abnormalities. Only seven had both abnormal HF volume ratios and T2 MRI (all
      increased HF T2 signal). There was a significant correlation between hippocampal
      volume and inferior mesial and lateral temporal lobe cerebral metabolic rate of
      glucose asymmetry index (p < 0.01), suggesting that hypometabolism may reflect
      hippocampal atrophy. PET is more sensitive than MRI volumetry in identifying the
      ictal focus but does not provide additional information when HF atrophy is
      present.

PMID- 7824102
TI  - Alterations of GABAergic neurons in the basal ganglia of patients with
      progressive supranuclear palsy: an in situ hybridization study of GAD67 messenger
      RNA.
AB  - We analyzed postmortem GABAergic neurons in the basal ganglia of three patients
      with progressive supranuclear palsy (PSP) and four matched controls by means of
      glutamic acid decarboxylase (M(r) 67,000 [GAD67]) mRNA in situ hybridization. In
      PSP, we found a 50 to 60% decrease in the number of neurons expressing GAD67 mRNA
      in the caudate nucleus, ventral striatum, and the external and internal pallidum.
      The expression of GAD67 mRNA per neuron was reduced in the caudate nucleus and
      putamen (-43%), the ventral striatum (-55%), and the external and internal
      pallidum (-59% and -68%). Our data indicate that striatal and pallidal GABAergic
      neurotransmission is markedly reduced in PSP and we suggest that this alteration
      may account for the motor and cognitive symptoms observed in PSP. Furthermore,
      the destruction of the basal ganglia output systems may explain the lack of
      responsiveness to L-dopa therapy of PSP patients.

PMID- 7824103
TI  - Genetic anticipation in Parkinson's disease.
AB  - We studied age at onset and family history of 137 patients (probands) with the
      diagnosis of idiopathic Parkinson's disease (PD). Probands (N = 21) who had an
      affected parent, aunt, or uncle were younger (p = 0.0001) at the onset of PD
      (47.7 +/- 8.8 years) than were probands (N = 11) who had an affected sib only
      (60.3 +/- 12.9 years) and probands (N = 105) who had no affected sib, parent,
      aunt, or uncle (59.2 +/- 11.4 years). Age at onset of affected family members
      differed significantly between generations (p = 0.0001). Age at onset was
      earlier, by an average of 17 years, in the proband generation than in the
      parental generation. The intrafamily variation in the calendar year of onset was
      too great to suggest a common point of exposure. Our data are most compatible
      with genetic anticipation, which could suggest involvement of an unstable
      trinucleotide repeat.

PMID- 7824104
TI  - Cerebrospinal fluid of Parkinson's disease patients inhibits the growth and
      function of dopaminergic neurons in culture.
AB  - We report the possible existence of an inhibitory factor in the CSF of
      Parkinson's disease patients that inhibits the function and growth of
      dopaminergic neurons in rat mesencephalic culture. After 40 hours' exposure to
      the < 10 kd fraction of CSF from PD patients, the high-affinity dopamine uptake
      was 66% of that of cultures exposed to CSF from controls. However, the number of
      dopaminergic neurons remained unchanged at this time. After 90 hours' exposure to
      the < 10 kd fraction of CSF from PD patients, the number of dopaminergic neurons
      decreased to 10% of that in cultures exposed to CSF from controls, and the size
      of the remaining dopaminergic neurons in the culture became smaller. This
      inhibitory factor did not affect the growth of other types of neurons. The
      chemical nature of this inhibitory factor is under investigation.

PMID- 7824105
TI  - DNA analysis in hereditary dentatorubral-pallidoluysian atrophy: correlation
      between CAG repeat length and phenotypic variation and the molecular basis of
      anticipation.
AB  - Hereditary dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant
      neurodegenerative disease with variable clinical phenotypes. Progressive ataxia,
      choreoathetosis, and dementia are the main clinical features of adult-onset
      cases, whereas the main feature in juvenile-onset DRPLA is progressive myoclonus
      epilepsy. Earlier onset is apparent in successive generations (anticipation). The
      molecular abnormality underlying DRPLA is an expanded, unstable CAG trinucleotide
      repeat on chromosome 12p. We analyzed 71 DNA samples obtained from 12 Japanese
      DRPLA pedigrees that included 38 affected individuals. Normal alleles had 7 to 23
      repeats, DRPLA alleles 53 to 88 repeats. DRPLA alleles also were detected in five
      asymptomatic family members. Patients with juvenile onset had significantly
      larger repeats than did those with adult onset, and there was a significant
      negative correlation between CAG repeat length and age at onset. In 80% of the
      paternal transmissions, there was an increase of more than five repeats, whereas
      all the maternal transmissions showed either a decrease or an increase of fewer
      than five repeats. There was a significant correlation between father-child
      differences in repeat length and differences in age at onset. The analysis of CAG
      repeat length is a reliable diagnostic test for DRPLA and is of value for the
      presymptomatic detection of individuals at risk. The expansion of CAG repeats is
      important in phenotypic variation and anticipation. In addition, the sex of the
      transmitting parent has a significant effect on the molecular mechanism of
      anticipation.

PMID- 7824106
TI  - Posterior agyria-pachygyria with polymicrogyria: evidence for an inherited
      neuronal migration disorder.
AB  - We describe two brothers with mental retardation and refractory epilepsy. MRI
      revealed symmetrical agyria-pachygyria of the temporo-occipito-parietal regions,
      areas of deeply infolded polymicrogyric parietal cortex, and dilated occipital
      horns (colpocephaly). The stereotyped clinical, EEG, and MRI findings suggest
      that this may be a distinct inherited condition and imply that agyria-pachygyria
      with polymicrogyria is not always sporadic.

PMID- 7824107
TI  - Dissociated changes of frontal and parietal somatosensory evoked potentials in
      sleep.
AB  - We studied the changes of frontal and parietal somatosensory evoked potentials
      (SEPs) in the awake state versus different stages of sleep in 10 normal adult
      subjects. Frontal and parietal SEP components were affected differentially as
      sleep stages progressed. In general, the amplitudes of frontal components,
      notably P22, were increased in sleep, whereas the amplitudes of parietal
      components were decreased in sleep. A sensitive waveform change from the awake
      state to sleep was present in the frontal response, where a subtle notched
      negativity, termed "N40," was present only in the awake state and quickly
      dissipated in all stages of sleep, including stage 1. The amplitude changes from
      the awake state to stage 3/4 sleep were neither linear nor parallel among SEP
      components. The most discordant changes occurred in stage 3/4. The amplitudes for
      the frontal N18-P22-N30 complex and parietal N20-P26-N32 complex increased from
      stage 2 to stage 3/4, while those for frontal N30-fP40 and parietal N32-pP40
      decreased. In contrast to these divergent amplitude changes, the latencies of all
      components except P14 and frontal N18 showed progressive prolongation from the
      awake state to slow-wave sleep. The SEP waveforms and latencies in REM sleep
      approximated those in the awake state, although amplitudes for frontal peaks
      still remained slightly higher and amplitudes for parietal peaks slightly lower.
      We postulate that interactions of excitatory and inhibitory phenomena are
      responsible for the component-dependent and sleep-stage-dependent amplitude
      enhancement or depression in sleep.

PMID- 7824109
TI  - Inoculation of nonhuman primates with the N40 strain of Borrelia burgdorferi
      leads to a model of Lyme neuroborreliosis faithful to the human disease.
AB  - We injected rhesus macaques with a highly infective strain of Borrelia
      burgdorferi to assess whether experimentally inoculated nonhuman primates (NHPs)
      could serve as models of human Lyme neuroborreliosis (LNB). The animals developed
      biopsy-confirmed erythema migrans in the area of the inoculations. ELISA testing
      of sera revealed strong antibody reactivity to B burgdorferi antigens, and
      Western blotting showed that 16-, 22-, 31-, 34-, and 41-kd proteins of the
      spirochete were major antigens recognized by antibody. Culture and polymerase
      chain reaction (PCR) testing of serial CSF specimens revealed that chronic
      infection of the CNS occurred in all NHPs injected. CSF pleocytosis occurred
      concurrently with CNS infection. Brain MRI revealed intense meningeal
      inflammation in one NHP as manifested by gadolinium uptake by the dura at the
      base of the temporal lobes. All animals had measurable antibody in the CSF after
      invasion. These studies are the first to demonstrate that experimental LNB in
      NHPs is a reliable model faithful to the human disease, with spirochetal invasion
      of the subarachnoid space. This also is the first report of CSF samples positive
      by culture in experimental LNB. Inflammation in the CNS as manifested by CSF
      pleocytosis and MRI findings was also correlated with the presence of spirochetal
      DNA detected by PCR. These data support the hypothesis that the pathogenesis of
      LNB is associated with direct spirochetal invasion, and provide evidence that CNS
      involvement is more common than heretofore thought.

PMID- 7824108
TI  - Glucose infusion paradoxically accelerates degradation of adenine nucleotide in
      working muscle of patients with glycogen storage disease type VII.
AB  - We investigated the effect of glucose infusion on adenosine triphosphate
      degradation in skeletal muscle of patients with glycogen storage disease type
      VII. Three patients and six healthy subjects exercised on a bicycle ergometer
      twice, once with 20% glucose infusion and once with saline infusion. The glucose
      infusion increased plasma glucose levels to 170 to 182 mg/dl and serum insulin
      levels to 30 to 50 microU/ml, while it markedly decreased plasma free fatty acid
      levels. The exercise-induced increases in plasma ammonia, inosine, and
      hypoxanthine were much larger with glucose than with saline infusion in the
      patients. Urinary excretion of inosine and hypoxanthine with glucose infusion was
      twice as high as that with saline infusion. No such differences were present
      between glucose and saline infusion in the healthy subjects. Glucose infusion
      therefore accelerates the energy crisis in working muscle of patients with
      glycogen storage disease type VII, probably due to a decrease in fatty acid
      utilization.

PMID- 7824110
TI  - Procedures for setting normal values.

PMID- 7824111
TI  - Multislice diffusion mapping for 3-D evolution of cerebral ischemia in a rat
      stroke model.
AB  - Diffusion-weighted magnetic resonance imaging (DWI) can quantitatively
      demonstrate cerebral ischemia within minutes after the onset of ischemia. The use
      of a DWI echo-planar multislice technique in this study and the mapping of the
      apparent diffusion coefficient (ADC) of water, a reliable indicator of ischemic
      regions, allow for the detection of the three-dimensional (3-D) evolution of
      ischemia in a rat stroke model. We evaluated 13 time points from 5 to 180 minutes
      after occlusion of the middle cerebral artery (MCA) and monitored the 3-D spread
      of ischemia. Within 5 minutes after the onset of ischemia, regions with reduced
      ADC values occurred. The core of the lesion, with the lowest absolute ADC values,
      first appeared in the lateral caudoputamen and frontoparietal cortex, then spread
      to adjacent areas. The volume of ischemic tissue was 224 +/- 48.5 mm3 (mean +/-
      SEM) after 180 minutes, ranging from 92 to 320 mm3, and this correlated well with
      the corrected infarct volume at postmortem (194 +/- 23.1 mm3, r = 0.72, p <
      0.05). This experiment demonstrated that 3-D multislice diffusion mapping can
      detect ischemic regions noninvasively 5 minutes after MCA occlusion and follow
      the development of ischemia. The distribution of changes in absolute ADC values
      within the ischemic region can be followed over time, giving important
      information about the evolution of focal ischemia.

PMID- 7824112
TI  - The CERAD experience, Part VIII: Neuroimaging-neuropathology correlates of
      temporal lobe changes in Alzheimer's disease.
AB  - We compared premortem neuroimaging findings with neuropathologic evidence of
      temporal lobe atrophy in 20 patients with Alzheimer's disease (AD) confirmed by
      autopsy. There were significant correlations between temporal horn enlargement
      observed by neuroimaging and hippocampal atrophy at autopsy, and between the
      overall cerebral atrophy severity on neuroimaging and scores on the Mini-Mental
      State Examination. This report confirms previous studies correlating temporal
      lobe atrophy on neuroimaging with a clinical diagnosis of AD, although more
      precise neuroimaging techniques are needed for use in multicenter studies of AD.

PMID- 7824113
TI  - High-resolution activation mapping of basal ganglia with functional magnetic
      resonance imaging.
AB  - We investigated the activation of the putamen and the external and internal
      division of the globus pallidus in 12 normal volunteers during rapid supination
      and pronation of their right or left hand, using functional MRI (fMRI). We
      observed an increase in signal intensity varying from 3.1 +/- 1.2% to 23.4 +/-
      2.3% during activation. Activated areas were predominantly contralateral to the
      moving hand and smaller than 5 mm2. These findings indicate that fMRI allows
      study of the normal function of basal ganglia and may be of value in the
      investigation of basal ganglia disorders.

PMID- 7824114
TI  - Degeneration of substantia nigra in chronic Parkinson's disease visualized by
      transcranial color-coded real-time sonography.
AB  - To detect morphologic abnormalities in Parkinson's disease (PD), we examined 30
      patients with PD and 30 age- and sex-matched nonparkinsonian controls by
      transcranial color-coded real-time sonography (TCCS). In 12 severely affected PD
      patients, the echogenicity of the substantia nigra was distinctly increased. In
      the remaining 18 PD patients and in all controls, the substantia nigra was poorly
      visualized or nondetectable by TCCS. The degree of hyperechogenicity of the
      substantia nigra closely correlated with the severity and duration of PD (p <
      0.001). The increased echogenicity of the substantia nigra notably results from
      nigral gliosis and reflects the stage of degeneration.

PMID- 7824116
TI  - Permanent hemiparesis due to partial status epilepticus.
AB  - Partial status epilepticus (SE) produces permanent focal neurologic deficits if
      it lasts for months or is associated with systemic illness or CNS inflammation.
      We describe a patient in focal SE for just 5 days. Attacks were her habitual
      frontal lobe seizures. When SE stopped, permanent contralateral hemiparesis was
      present. There was no new cause for the weakness except the SE itself. We
      conclude that partial SE requires prompt and effective treatment, since it can
      lead to permanent neurologic dysfunction.

PMID- 7824115
TI  - Involuntary movement disorders associated with felbamate.
AB  - Two children developed involuntary movements while taking felbamate as an adjunct
      to their antiepileptic regimen. One exhibited choreoathetosis and the other an
      acute dystonic reaction. In both children the symptoms resolved with no
      recurrence after felbamate discontinuance.

PMID- 7824117
TI  - Reversible periodic alternating gaze deviation in hepatic encephalopathy.
AB  - We report two patients with hepatic encephalopathy who developed periodic
      alternating gaze deviation (PAGD). Neither patient had an evident structural
      lesion, and the PAGD subsided after treatment of the encephalopathy. We postulate
      that a GABA-mediated disturbance affecting the cerebellar nodulus and uvula was
      responsible for the PAGD in these patients.

PMID- 7824118
TI  - Detection of Strongyloides stercoralis in the cerebrospinal fluid of a patient
      with acquired immunodeficiency syndrome.
AB  - We report a case of Strongyloides stercoralis hyperinfection syndrome in a
      patient with acquired immunodeficiency syndrome with CNS involvement who died
      despite prompt institution of thiabendazole.

PMID- 7824119
TI  - Idiopathic CD4+ T-cell lymphocytopenia and subacute inflammatory demyelinating
      polyradiculoneuropathy.

PMID- 7824120
TI  - Mitochondrial abnormalities are not invariably present in neurologic syndromes
      associated with multiple symmetric lipomatosis.

PMID- 7824121
TI  - Phenytoin neurotoxicity from illicit use.

PMID- 7824122
TI  - Multiple sclerosis in Spain.

PMID- 7824123
TI  - Smooth pursuit in progressive supranuclear palsy.

PMID- 7824124
TI  - Arm rolling test.

PMID- 7824125
TI  - Idiopathic recurring stupor.

PMID- 7824126
TI  - Imaging back pain.

PMID- 7824127
TI  - Physical therapy in Parkinson's disease.

PMID- 7824128
TI  - Clinical, neuropathologic, and genetic studies of a large spinocerebellar ataxia
      type 1 (SCA1) kindred: (CAG)n expansion and early premonitory signs and symptoms.
AB  - We report the clinical, neuropathologic, and genetic studies of a large kindred
      (family M-ADCA1) with autosomal dominant spinocerebellar ataxia type 1 (SCA1),
      ascertained in 41 members, with clinical data available in twenty-two. The mean
      age of onset was 36.3 +/- 6.2 years (ages, 26 to 52), the mean duration of the
      disease was 15.8 +/- 6.5 years (range, 10 to 28 years), and the mean age at death
      was 54.1 +/- 9.5 years (ages, 39 to 72). Premonitory signs and symptoms appeared
      earlier than the usual onset symptoms in many of the clinically unaffected
      patients who inherited the mutated SCA1 gene. Anticipation was present when we
      compared the seventh and eighth generations. A more severe course of the disease
      occurred in offspring of affected males. Neuropathologic examination, performed
      on three patients, showed the usual findings of SCA1; Golgi and
      immunocytochemistry studies suggested primary damage of the Purkinje cells. We
      analyzed the CAG-repeat mutation responsible for the SCA1 phenotype in a total of
      41 family members. There was expansion in 19 subjects (10 clinically affected,
      seven with early signs and symptoms, and two asymptomatic individuals), and all
      showed heterozygosity, with one allele between 41 and 59 repeats (SCA1 mutation)
      and the other in the range of 6 to 39 repeats (normal range). The clinical
      analysis of "at risk" patients with the SCA1 mutation showed that minor signs and
      symptoms begin before full clinical diagnosis, and these premonitory
      manifestations can herald full development of SCA1 by years.

PMID- 7824129
TI  - Assessment of MRI criteria for MS in Japanese MS and HAM/TSP.
AB  - We evaluated the usefulness of the MRI criteria for multiple sclerosis (MS)
      proposed by Paty et al and Fazekas et al in 36 Japanese MS patients, using HTLV-I
      associated myelopathy (HAM)/tropical spastic paraparesis (TSP) as the control.
      Although 30 of 36 HAM/TSP patients had multiple white matter lesions on T2
      weighted cranial MRI, only two fulfilled the MRI criteria for MS. At the same
      time, 31 of the 36 MS patients fulfilled the primary MRI criterion, yielding 93%
      specificity and 86% sensitivity for the criterion. MS has disease-specific MRI
      abnormalities.

PMID- 7824130
TI  - Familial hemiplegic migraine versus migraine with prolonged aura: an uncertain
      diagnosis in a family report.
AB  - Four of five members of a family complained of repeated attacks of hemiplegic
      migraine, migraine with aura of different types, or migraine without aura. The
      hemiplegia always outlasted the headache and was often accompanied by altered
      consciousness, aphasia, and, in one patient, coma; in this latter patient, the
      ictal EEG, recorded during two attacks, showed delta activity in the hemisphere
      contralateral to the hemiplegia. At least 2 months after their latest attacks,
      three patients showed dyscalculia, attentional disturbances, and impaired long
      term verbal memory on neuropsychologic assessment. There were no cognitive
      disturbances in the unaffected relative. The severity of cognitive impairment
      appears to be correlated with migraine history. We attempt to classify these
      cases according to the criteria of the International Headache Society.

PMID- 7824131
TI  - Subcortical aphasia: distinct profiles following left putaminal hemorrhage.
AB  - Numerous reports of aphasia after subcortical lesions have produced incomplete
      agreement about basic clinico-anatomic correlations. Some disagreement has arisen
      from methodologic differences. To control for some of the common differences, we
      analyzed 13 patients with left putaminal hemorrhage controlled for location-
      subcortical but not thalamic, and for time postonset--studied in both acute and
      postacute epochs. There was no apparent correlation between lesion site and acute
      language profiles. During the postacute epoch, there were several distinct
      correlations between lesion site (postacute decreased CT density) and specific
      aphasia dimensions--nonfluency, impaired comprehension, and perhaps impaired
      repetition. Our correlations were compatible with comparably controlled cases in
      the literature. A corollary result of this study is that patients fluent during
      the early epoch are likely to have a better outcome, and those initially
      nonfluent have a poor prognosis for language recovery.

PMID- 7824132
TI  - Rotational vertigo in embolic stroke of the vestibular and auditory cortices.
AB  - We describe the unique case of a woman with embolic infarction within the right
      middle cerebral artery territory who had nonepileptic rotational vertigo, nausea,
      and unsteady gait that gradually resolved within a week. A well-demarcated lesion
      of the posterior insula (homologous to parieto-insular vestibular cortex in
      monkeys) was probably the cause. This is supported by a contraversive tilt of
      perceived vertical and by involvement of the adjacent auditory (Heschl's) cortex.
      Dipole source analysis of late auditory evoked potentials revealed a decreased
      amplitude of a dipole source in the right insular cortex, whereas two other
      dipoles situated in the temporal lobe showed symmetric activity.

PMID- 7824133
TI  - Anterior communicating artery aneurysm paraparesis syndrome: clinical
      manifestations and pathologic correlates.
AB  - OBJECTIVE: Clinicopathologic evaluation of patients with lower extremity
      paraparesis/-plegia following rupture and repair of anterior communicating artery
      (ACoA) aneurysms. DESIGN: Institution-based retrospective review. SETTING: A
      tertiary neurologic referral center. PATIENTS, PARTICIPANTS: Seven of 101
      patients with subarachnoid hemorrhage from ruptured ACoA aneurysms treated
      between January 1987 and December 1992. MAIN OUTCOME MEASURES: Neurologic status
      at latest follow-up examination. RESULTS: All patients presented with severe
      hemorrhage, poor clinical grade, and intracranial hypertension. Motor deficits
      developed within 7 days of aneurysm rupture and persisted for a mean duration of
      39 days. Angiographic evidence of vasospasm in the anterior cerebral artery (ACA)
      distribution was documented in all cases, and paraparesis persisted beyond the
      angiographic resolution of vasospasm. All patients had evidence of frontal lobe
      dysfunction throughout their postoperative courses, and deep venous thrombosis
      and pulmonary emboli were common causes of morbidity and mortality. Autopsy data
      supported regional microvascular ischemia within the ACA distribution as the
      etiology of these motor deficits. CONCLUSIONS: The combination of vasospasm in
      the ACA distribution and lower extremity weakness associated with cognitive and
      affective impairment that resolves with time is common in patients with ACoA
      aneurysms. We propose that this constellation of clinical, radiographic, and
      pathologic findings be referred to as the "ACoA aneurysm paraparesis syndrome."

PMID- 7824134
TI  - Nonsteroidal anti-inflammatory drugs in Alzheimer's disease.
AB  - We reviewed the records of 210 patients in the Johns Hopkins Alzheimer's Disease
      Research Center to evaluate the role of nonsteroidal anti-inflammatory drugs
      (NSAIDs) on clinical features and progression of the disease. We compared
      patients taking NSAIDs or aspirin on a daily basis (N = 32) to non-NSAID patients
      (N = 177) on clinical, cognitive, and psychiatric measures. The NSAID group had a
      significantly shorter duration of illness at study entry. Even after controlling
      for this difference, the NSAID group performed better on the Mini-Mental State
      Examination, Boston Naming Test, and the delayed condition of the Benton Visual
      Retention Test. Furthermore, analysis of longitudinal changes over 1 year
      revealed less decline among NSAID patients than among non-NSAID patients on
      measures of verbal fluency, spatial recognition, and orientation. These findings
      support other recent studies suggesting that NSAIDs may serve a protective role
      in Alzheimer's disease.

PMID- 7824135
TI  - Relationship between lifetime occupation and parietal flow: implications for a
      reserve against Alzheimer's disease pathology.
AB  - We previously reported an inverse relation between parietal cerebral blood flow
      and years of education in Alzheimer's disease (AD) patients matched for clinical
      severity. This suggested that the clinical manifestation of advancing AD
      pathology is delayed in patients with higher educational attainment. Other
      aspects of life experience may also provide a reserve against the clinical
      expression of AD. To test this hypothesis, we classified the primary life-time
      occupations of 51 AD patients using the Dictionary of Occupational Titles,
      published by the US Department of Labor, and derived six factor scores describing
      intellectual, interpersonal, and physical job demands. Regional cerebral blood
      flow was measured using the xenon-133 inhalation method. After controlling for
      age, clinical dementia severity, and education, there was less relative perfusion
      in the parietal region in subjects whose occupations were associated with higher
      interpersonal skills and physical demands factor scores. We conclude that
      independent of education, aspects of occupational experience may provide a
      reserve that delays the clinical manifestation of AD.

PMID- 7824136
TI  - Idiopathic intracranial hypertension associated with tetracycline use in
      fraternal twins: case reports and review.
AB  - Fraternal twin sisters developed idiopathic intracranial hypertension (IIH)
      shortly after beginning tetracycline for treatment of acne. We reviewed from the
      literature 19 familial cases of IIH and 37 cases of IIH associated with
      tetracycline usage. Among the 37 combined adult and pediatric cases, 26 of 37 had
      resolution of signs or symptoms of IIH within hours to days of stopping the
      antibiotic, and rapid recurrence with reinitiation of drug occurred in 4 of 37.
      We suggest that these cases may be tetracycline-induced, may be related to an
      underlying genetic susceptibility, and support the notion of multifactorial
      etiologies for IIH.

PMID- 7824137
TI  - Automatisms with preserved responsiveness: a lateralizing sign in psychomotor
      seizures.
AB  - This is a report of a 1-year prospective study to investigate how often
      automatisms occur with preserved responsiveness in psychomotor seizures.
      Responsiveness is usually impaired or lost when automatisms occur during
      psychomotor seizures. However, there are several anecdotal reports in the
      literature of patients who have automatisms with preserved responsiveness (APRs).
      We evaluated 123 patients with temporal lobe epilepsy (57 patients [46%] left
      sided, 48 patients [39%] right-sided, and 18 patients [15%] bitemporal) with
      video/EEG monitoring, testing responsiveness by asking the patient to respond
      verbally and to follow motor commands. Seven patients (5.6%) had preserved
      responsiveness in the presence of prominent automatisms (lip smacking,
      swallowing). In 15 seizures, the responsiveness was adequately tested (3.6
      questions per period of automatism). Average seizure duration was 71.6 +/- 14.8
      seconds (range, 45 to 100 seconds). Average duration of automatisms was 59.5 +/-
      13.5 seconds (range, 40 to 80 seconds). Ictal EEG was localized over the right
      temporal area in nine seizures, over the right hemisphere in five, and was
      nonlocalizable in one seizure. APRs never occurred in left-sided psychomotor
      seizures and occurred in 10% of the right temporal cases. In conclusion, APRs
      reliably lateralized to the right side in temporal lobe epilepsy.

PMID- 7824138
TI  - Dissociation of anosognosia for hemiplegia and aphasia during left-hemisphere
      anesthesia.
AB  - The stroke literature indicates that the explicit denial of hemiplegia, a form of
      anosognosia, is associated more commonly with right- than left-hemisphere
      lesions. Some investigators have suggested that this asymmetry may be an artifact
      and that the aphasia that often accompanies left-hemisphere dysfunction may mask
      some instances of anosognosia. Mechanisms suggested for anosognosia have been
      either "global" or "modular" in nature. Mechanisms posited in global explanations
      include psychological denial and general mental deterioration; modular
      explanations include feedback and feedforward theories. Videotapes of 54 patients
      with medically intractable seizures who had selective barbiturate anesthesia
      (Wada test) as part of their evaluation for seizure surgery were assessed for
      anosognosia of hemiplegia and aphasia after hemispheric anesthesia had worn off.
      The results suggest that, although aphasia may confound the reported rate of
      anosognosia for hemiplegia following left-hemisphere dysfunction, the frequency
      of anosognosia for hemiplegia is still higher with right- than left-side
      dysfunction. Anosognosia for hemiplegia and aphasia were dissociable, providing
      support for the postulate that awareness of dysfunction is mediated by a modular
      system.

PMID- 7824139
TI  - Visual field loss in senile dementia of the Alzheimer's type.
AB  - BACKGROUND: Visual performance is impaired in patients with senile dementia of
      the Alzheimer's type (SDAT). We investigated the visual field topography of these
      deficits. METHODS: Humphrey automated perimetry (Program 30-2) was used to
      measure differential luminance sensitivity within the central 60 degrees of the
      visual field in SDAT patients (n = 61) and in visually and cognitively normal
      volunteer subjects of similar age (n = 61). Twenty-three SDAT patients were
      retested 18 months after the original examination. RESULTS: Reliable visual
      fields (by manufacturer's criteria) were obtained in 72.1% (44/61) of the control
      subjects and 55.7% (34/61) of the SDAT group. In the SDAT group, differential
      luminance sensitivity was significantly reduced relative to the control group.
      Visual sensitivity was reduced throughout the visual field, but deficits were
      most pronounced in the inferior visual field, where they presented most commonly
      as arcuate defects. Patients with more severe dementia exhibited greater
      reductions in visual sensitivity. On follow-up, 14 of 23 SDAT patients exhibited
      progression of visual field loss, whereas only two of 23 patients exhibited a
      regression of the visual field loss. CONCLUSIONS: Although automated perimetry
      requires considerable patient cooperation, many patients with SDAT can produce
      reliable visual field results. These patients exhibit significant reductions in
      global sensitivity. Visual field loss in SDAT is most pronounced in the
      inferonasal and inferotemporal arcuate regions of the visual field but also
      involves the central field.

PMID- 7824140
TI  - The prevalence of dementia is changing over time in Rochester, Minnesota.
AB  - Resources of the Rochester Epidemiology Project were used to estimate prevalence
      rates for dementia on January 1, 1975, 1980, and 1985, and to evaluate trends
      over time. Prevalence rates increased with age for both men and women. There was
      no difference in the prevalence rates for January 1, 1975, and January 1, 1980,
      but there was a significant increase between January 1, 1980, and January 1,
      1985. Similar results were found for Alzheimer's disease. Age was an important
      factor in the trend data. The apparent increase in prevalence over time is
      probably multifactorial.

PMID- 7824141
TI  - A large pedigree with early-onset Alzheimer's disease: clinical, neuropathologic,
      and genetic characterization.
AB  - We present clinical, neuropsychological, and neuropathologic data on a large
      pedigree including 34 subjects with early-onset progressive dementia. The mean
      (+/- SD) age at onset was 46 +/- 3.5 years and the mean age at death 52.6 +/- 5.7
      years. Twelve patients were clinically diagnosed as having probable Alzheimer's
      disease (AD) according to the NINCDS-ADRDA criteria. Neuropsychological
      evaluation, performed at a moderate stage of the disease, was available in six
      subjects and showed a classic pattern of cognitive deficit. Myoclonus and
      extrapyramidal signs were common, and seizures were present in all affected
      subjects. There were neuropathologic changes typical of AD in two brains. A
      significant lod score of 5.48 was observed at a recombination fraction of theta =
      0.0 with the genetic marker D14S43, thereby establishing that the responsible
      gene was located on chromosome 14q24.3. These results suggest that epilepsy could
      represent a particular feature in AD families linked to chromosome 14q.

PMID- 7824142
TI  - An aspect of sentence processing in Alzheimer's disease: quantifier-noun
      agreement.
AB  - We assessed sentence processing in Alzheimer's disease (AD) with measures of
      sentence-picture matching, grammaticality judgments of sentences, and sentence
      completion. The results demonstrated significant and consistent difficulty with a
      grammatical feature of sentences on all three experiments. This impairment could
      not be explained by factors such as sentence length, dementia severity, or a
      short-term memory deficit and was independent of difficulty interpreting the
      meanings of words. We hypothesize that AD patients are impaired at appreciating
      the conceptual relations that underlie certain grammatical features of sentences.

PMID- 7824143
TI  - The Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) as a
      screening tool for dementia for a predominantly illiterate Chinese population.
AB  - The Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) provides
      ratings of an individual's changes in everyday cognitive functions during the
      previous 10 years. Original studies conducted in Australia showed that its score
      was not influenced by the subjects' educational backgrounds and that it performed
      at least as well as the Mini-Mental State Examination (MMSE) as a screening
      instrument for dementia. The subjects of the present study were Chinese and
      included 399 community residents and 61 dementia patients. Their ages ranged from
      50 to 92 years; their education levels ranged from 0 to 19 years, and 63% of them
      had never attended school. We administered the IQCODE to informants and the
      Cognitive Abilities Screening Instrument (CASI), from which a CASI-estimated
      score of the MMSE (MMSE-CE) can be obtained, to the subjects. The diagnosis of
      dementia was made independently by physicians according to the DSM-III-R criteria
      based on semistructured interview and testing, neurologic examination, and
      standardized assessments of cerebral vascular disease, Parkinson's disease, and
      depression. The Chinese IQCODE showed no association with the subjects' education
      level or gender, low association with their age, and moderately high association
      with their MMSE-CE score. The area under the receiver operating characteristic
      curve of the IQCODE was significantly larger than that of the MMSE-CE for the
      whole group and for the subgroup with 1 to 19 years of education but not for the
      subgroup with 0 years of education. Nine of the 26 items of the IQCODE could be
      deleted without appreciable reduction in sensitivity and specificity. The IQCODE
      (1) can be shortened to 17 items, (2) had good cross-cultural applicability, and
      (3) was better than the MMSE-CE as a screening tool for dementia in a population
      with large variation in educational backgrounds.

PMID- 7824144
TI  - Apolipoprotein E genotype and Lewy body disease.
AB  - To determine whether apolipoprotein E (APOE) genotype affects neuropathology in
      Lewy body disease (LBD), we examined 18 cases of LBD that did not have concurrent
      Alzheimer's disease by the CERAD criteria. We obtained APOE genotypes, determined
      diffuse beta-amyloid plaque (A beta P) and Lewy body densities in multiple brain
      regions, and graded the intensity of CA2-3 ubiquitin-positive neurites, vacuolar
      change, nigral pathology, amyloid angiopathy, and subpial amyloid deposition. The
      APOE allele frequencies were as follows: epsilon 2, 0.14 +/- 0.07; epsilon 3,
      0.64 +/- 0.08; and epsilon 4, 0.22 +/- 0.03. The mean A beta P density was lower
      in APOE epsilon 3/3 cases (14.5 A beta Ps per mm2) than in the groups with the
      APOE epsilon 2 (67.0) or APOE epsilon 4 (46.6) alleles. This difference was due
      largely to the difference between A beta P density in the APOE epsilon 2 group
      and the APOE epsilon 3/3 group (F = 5.525, p < 0.02). CA2-3 neuritic degeneration
      was greater in those with the APOE epsilon 4 allele than in those with the APOE
      epsilon 3/3 genotype (grade = 1.9 +/- 1.3 versus 0.938 +/- 0.9; Kruskal-Wallis
      test statistic = 6.962, p < 0.05). These data are consistent with the hypothesis
      that APOE genotype may affect neuropathology in LBD.

PMID- 7824145
TI  - Triage of American combat casualties: the need for change.
AB  - United States military medical planning must reevaluate the practices of combat
      casualty resuscitation, transportation, and triage to secondary echelon care.
      Analysis of the experiences of other medical commands, such as that of the
      Israeli Defense Force, offers insight into improvements in equipment and training
      that are achievable with minimal cost. Training programs must involve formal
      instruction in Advanced Trauma Life Support for the combat corpsman, and ongoing
      experience in trauma surgery for personnel who are placed in the role of military
      surgeons. Today in military medicine there exists a major deficiency of expertise
      in trauma care, arising through a near total lack of involvement in active trauma
      surgery on the part of military medical training facilities. Civilian trauma
      centers offer an abundance of opportunity for military-like casualty management,
      and successful efforts at our command have integrated active duty personnel into
      this experience.

PMID- 7824146
TI  - Clinical case management in the Army medical department.
AB  - Clinical case management is a system that has the potential to improve the
      efficiency and effectiveness of health care delivery. Given this potential, the
      Army Medical Department (AMEDD) is examining this process as a means to achieve
      goals of quality care and cost effectiveness. In this article, the authors
      describe the concept of case management, the AMEDD system of clinical case
      management, the implementation of clinical case management in the AMEDD, and the
      role of the case manager.

PMID- 7824147
TI  - Demonstration of a neural network expert system for recognition of glaucomatous
      visual field changes.
AB  - Expert systems (ESs) are computer programs designed to make decisions in a manner
      similar to the way human experts make them. There are many forms of ESs, ranging
      from those that are given specific If-Then rules to those that are capable of
      deriving their own rules. Some ESs use neural network simulations to analyze
      patterns of data. In this project, a commercially available neural network shell
      program was used to demonstrate the development of an ES capable of analyzing the
      visual field loss patterns produced by glaucoma. Potential applications of ESs
      for the diagnosis of glaucoma are discussed.

PMID- 7824148
TI  - Pharmacy operations in the second infantry division.
AB  - A forward-deployed infantry division offers many challenges to its medical
      elements. These elements work in a peacetime environment providing quality
      medical care while preparing and training for a wartime mission to conserve the
      fighting strength. Pharmacy operations play significant roles in the
      accomplishment of both missions. The roles of the Division Pharmacist and the
      provision of pharmacy services in the Second Infantry Division are discussed.

PMID- 7824149
TI  - Quality and adequacy of training of expanded function dental auxiliaries in the
      U.S. Army.
AB  - This study explores the quality and adequacy of training U.S. Army expanded
      function dental auxiliaries (X2s). Data were collected in the spring of 1989
      using self-administered questionnaires from dental commanders, clinic chiefs, X2
      graduates, dentists working with X2s, and potential X2 students. Nearly all
      (94.2%) dental activities personnel responded. Results show overall performance
      of X2s was rated excellent or very good by 76% of commanders, 70% of clinic
      chiefs, and 42% of dentists. Of 23 job-specific tasks assessed, X2s received
      lowest performance ratings for placement of complex composite restorations and
      highest ratings for individual topical fluoride application. Of X2 graduates, 82%
      rated the overall quality of X2 training as very good or excellent. X2 graduates
      and their supervisors recommend retaining each job-specific skill in the X2
      training program while lengthening the program from 16 to 28-30 weeks. Training
      of U.S. Army X2s may offer a model to other dental care systems with limited
      resources.

PMID- 7824150
TI  - Nitroglycerin-induced heparin resistance: absence of interaction at clinically
      relevant doses.
AB  - A diminution in the anticoagulant effect of IV heparin with concomitant use of IV
      nitroglycerin has been reported. However, recent reports have disputed the
      existence of this interaction. The objective of this study was to assess the
      potential interaction of these agents in a clinical setting. Forty-five patients
      hospitalized with angina or acute myocardial infarction received low-dose
      nitroglycerin (5-20 micrograms/minute), and 13 received high-dose nitroglycerin
      (80-240 micrograms/minute). The two groups were similar with respect to sex, age,
      weight, and angina class; however, the high-dose group had a greater degree of
      congestive heart failure. The heparin dose required to achieve therapeutic
      anticoagulation did not differ between the groups. Results suggest no inhibition
      of heparin anticoagulation by IV nitroglycerin at clinically relevant doses.

PMID- 7824152
TI  - Pregnancy outcome in military and civilian women.
AB  - Physical and medical risk factors have long been linked to prematurity and
      intrauterine growth retardation. Recently, out-of-home employment has been cited
      as an additional risk. The primary objective of this investigation was to compare
      pregnancy risks and birth outcome in two groups of employed women (one military
      and one civilian). We performed a prenatal survey and a postpartum chart review
      and found that active duty military women worked longer into pregnancy and
      reported lower levels of social support than their civilian counterparts.
      However, infant weight and gestational age were not significantly different in
      the two groups.

PMID- 7824151
TI  - Development of a user-defined surgical database using a personal computer
      network.
AB  - Advances in personal computer technology have made powerful methods for the
      collection and analysis of patient information available to clinical users. This
      report details the development of a multi-user database distributed across a
      network of personal computers that facilitates operative scheduling, and
      collection and analysis of operative data. Clinicians from each surgical service
      in our medical center developed customized data entry programs that contribute
      information centrally through a telephone-line network to prepare the daily
      operative schedule. Subsequently, information from the operating rooms is added
      to the preoperative database to form an operative log, which is distributed to
      client services for further analysis and modification. This system has improved
      the efficiency and accuracy of operative scheduling and information management
      and shifted the burden of data collection away from the physician. Widespread
      availability of these data has contributed to the development of an effective
      quality improvement program and facilitated effective management of personnel and
      resources.

PMID- 7824153
TI  - Epstein-Barr virus infection in Desert Storm reservists.
AB  - Approximately 150 U.S. Army reservists from Indiana reported symptoms consistent
      with chronic fatigue syndrome after returning stateside from the tour of duty in
      Saudi Arabia. A psychiatric team confirmed the diagnosis, evaluated possible
      etiology, and treated the service members when appropriate. Those available
      service members who met the study's diagnostic criteria for chronic fatigue
      syndrome (n = 37) received an Epstein-Barr virus panel. Seventy-three percent of
      these selected service members were positive either for an acute or reactivated
      Epstein-Barr viral infection. These data suggest that service members who suffer
      from chronic fatigue syndrome may have their symptoms increased and prolonged by
      secondary viral infections.

PMID- 7824154
TI  - Incarceration of the gravid uterus due to an impacted leiomyoma: a case report.

PMID- 7824155
TI  - Isolated galactorrhea in sarcoidosis: a case report.
AB  - Neuroendocrine disorders are rare. A case of hypothalamopituitary sarcoidosis is
      presented in which hyperprolactinemia and galactorrhea occurred in isolation.

PMID- 7824156
TI  - The role of 5-HT1A serotonin and D2 dopamine receptors in buspirone effects on
      cortical electrical activity in rats.
AB  - The effects of buspirone (5 and 10 mg/kg i.p.), 8-OH-DPAT (0.25 mg/kg) and
      raclopride (2.5 mg/kg) on the EEG power spectra of the sensorimotor cortex were
      studied in freely moving rats. Buspirone (5 mg/kg) and 8-OH-DPAT produced
      selective slowing of the theta-activity. Buspirone (10 mg/kg) produced slowing of
      the theta-activity and increased the power of the alpha-band (9-11 Hz).
      Raclopride alone did not influence EEG power spectra. Simultaneous injection of 8
      OH-DPAT and raclopride produced marked slowing of the theta-activity and
      increased the power of the alpha-band. The role of 5 HT1A and D2 dopamine
      receptors in buspirone effects on cortical electrical activity in rats was
      discussed.

PMID- 7824157
TI  - ApoE allele frequencies in Italian sporadic and familial Alzheimer's disease.
AB  - Recent studies have provided evidence of association of apolipoprotein E (ApoE)
      epsilon 4 allele and late onset familial and sporadic Alzheimer's disease (AD).
      Epidemiological studies have established allelic variation at the ApoE locus. We
      have analyzed the ApoE gene polymorphism in a sample of 446 Italian subjects. Our
      data confirm a significant association between epsilon 4 allele and sporadic AD.
      The frequency of epsilon 4 allele in early onset familial AD patients was
      comparable to control values suggesting that epsilon 4 allele does not represent
      a risk factor for early onset familial AD (EOFAD). Moreover, we found a not
      previously reported association between ApoE epsilon 2 allele and sporadic AD and
      EOFAD.

PMID- 7824158
TI  - Evidence for brain docosahexaenoate recycling in the free-moving adult rat:
      implications for measurement of phospholipid synthesis.
AB  - The specific activity (SA) of unesterified docosahexaenoic acid (22:6 n-3) in the
      brain and arterial plasma was measured after constant intravenous infusion of
      [3H] 22:6 n-3 in the free-moving rat. Within 40-105 min, an apparent steady state
      of labeled unesterified 22:6 n-3 in plasma and in brain was reached. However, the
      values of the brain to plasma 22:6 n-3 SA ratios ranged from 0.03 to 0.05,
      indicating that an isotopic equilibrium between brain and plasma was not
      attained. This suggests that a considerable endogenous source of unesterified
      22:6 n-3 (95-97%) (likely derived from lipid metabolism) dilutes the SA of the
      tracer coming from plasma. Using the SA of 22:6 in plasma instead of brain would
      thus lead to a gross underestimation of the rate of phospholipid synthesis.

PMID- 7824159
TI  - Neurofibrillary tangles without cell loss in the lateral vestibular nucleus of
      patients with Alzheimer's disease.
AB  - The lateral vestibular nucleus (LVN, nucleus of Deiters) was examined in the
      brains of four control subjects and four patients with dementia of the Alzheimer
      type (DAT). Neuronal counts on sections stained with silver and a polyclonal
      antibody to human choline acetyltransferase (ChAT) revealed an undiminished
      number of LVN neurons in patients with DAT. Numerous silver-stained
      neurofibrillary tangles (NFTs) were found in the DAT group, some also in the LVN
      of controls. These findings suggest that DAT affects LVN neurons, however without
      causing neuronal loss.

PMID- 7824160
TI  - Effect of the R(-) and S(+) isomers of MDA and MDMA on phosphatidyl inositol
      turnover in cultured cells expressing 5-HT2A or 5-HT2C receptors.
AB  - The effect of the R(-) and S(+) isomers of 3,4-methylenedioxyamphetamine (MDA)
      and its N-methyl analog 3,4-methylenedioxymethamphetamine (MDMA) on [3H]inositol
      monophosphate accumulation was studied in cells expressing either 5-HT2A or 5
      HT2C receptors. The isomers of MDA produced a concentration dependent increase in
      phosphatidyl inositol (PI) hydrolysis at the 5-HT2A receptors, with the R(-)
      isomer of MDA being more potent than the S(+) at the 5-HT2A receptor. The R(-)
      and S(+) isomers of MDMA were significantly less efficacious at the 5-HT2A
      receptor as compared to MDA; S(+)MDMA had no effect. At the 5-HT2C receptor, both
      R(-) and S(+)MDA were equipotent at stimulating PI hydrolysis, with the S(+)
      isomer of MDMA being more efficacious at the 5-HT2C receptor compared with the R(
      ) isomer. In all cases at both the 5-HT2A and 5-HT2C receptors, the affinities of
      the isomers of MDMA and MDA were at least 2-3 orders of magnitude less than 5-HT.
      Despite the weak effect of these compounds at the 5-HT2A and 5-HT2C receptors,
      these substituted amphetamines do possess intrinsic activity which may contribute
      to their neurotoxic effects when administered at high doses.

PMID- 7824161
TI  - Developmental changes of nerve growth factor levels in the gracile axonal
      dystrophy mouse.
AB  - Nerve growth factor (NGF) levels were measured in various tissues of the gracile
      axonal dystrophy (GAD) mouse. When the disease had fully progressed, the NGF
      levels in the skeletal muscle, dorsal root ganglion and the spinal cord were
      decreased. These findings suggest that a reduction of the NGF level is involved
      in the pathophysiological processes in the GAD mouse.

PMID- 7824162
TI  - Pancreastatin-like immunoreactivity of cerebrospinal fluid in patients with
      Alzheimer type dementia: evidence of aberrant processing of pancreastatin in
      Alzheimer type dementia.
AB  - The concentrations of pancreastatin-like immunoreactivity (PST-LI) of the
      cerebrospinal fluid (CSF) were measured in the patients with Alzheimer type
      dementia (ATD) and in age-matched normal subjects. The mean PST-LI concentration
      in the CSF of ATD patients was significantly lower than that of normal subjects.
      Gel chromatographic analysis revealed that the main PST-LI peak of ATD's CSF
      eluted at molecular weight (MW) 13.5 kDa. However, the age-related change of the
      molecular forms of PST-LI in CSF was observed in normal subjects as following;
      PST-LI in neonatal CSF showed one peak at MW 13.5 kDa, that of 16-64-year-old
      showed two peaks at MW 13.5 and 5.4 kDa, however, only one main peak was shown at
      MW 5.4 kDa in the CSFs of 72-85-year-old. These findings suggest that the
      production of PST-LI was decreased and the proteolytic cleavage, which should
      process big PST to PST (1-52) in normal subjects, was altered to that of neonatal
      type in the CNS of the patients with ATD.

PMID- 7824163
TI  - Prolonged production of hydroxyl radical in rat hippocampus after brain ischemia
      reperfusion is decreased by 21-aminosteroids.
AB  - Transient global ischemia may lead to persistent production of reactive oxygen
      species in selected brain regions thereby contributing to selective vulnerability
      to ischemia. Using cerebral microdialysis, we assessed the production of the
      highly reactive hydroxyl radical (OH.) in rat hippocampus during global ischemia
      and reperfusion (IR). During IR, perfusate containing salicylic acid was
      collected and analyzed for non-enzymatic hydroxylation of salicylate to 2,3-DHBA.
      Since 21-aminosteroids can attenuate excitatory amino acid-mediated OH.
      production in the brain, we repeated the experiments after administration of the
      21-aminosteroid, U-74389G. The data indicate that 2,3-DHBA level increased
      progressively between 15 and 60 min after reperfusion, reaching values nearly
      three times the baseline value at 60 min. U-74389G, given 30 min before ischemia,
      greatly attenuated the increase in 2,3-DHBA during reperfusion. This is the first
      evidence for prolonged OH. production in the hippocampus after reperfusion in
      vivo which can be prevented by 21-aminosteroids.

PMID- 7824164
TI  - Tyrosine hydroxylase activity in peripherally denervated rat pineal gland.
AB  - The presence of tyrosine hydroxylase (TH) in the rat pineal gland was studied
      using a combination of immunochemical and biochemical methods. In superior
      cervical ganglionectomized (SCGx) animals and in isolated pineals incubated for
      72 h, both TH immunoreactive (TH-IR) fibers and TH biochemical activity were
      still present but reduced. Conversely, in dispersed pinealocytes incubated for
      only 24 h we were unable to detect either TH activity or TH-positive cells. Since
      in the pineal gland of intact rats total 3-methoxy-4-hydroxy phenylglycol (MHPG)
      was undetectable, and only traces of norepinephrine (NE) were present in the
      pineal of ganglionectomized animals, the results suggest a central pinealopetal
      catecholaminergic pathway which could use dopamine as a neurotransmitter.

PMID- 7824166
TI  - Remarkable reduction in acetylcholine concentration in the cerebrospinal fluid
      from patients with Alzheimer type dementia.
AB  - We determined the concentrations of acetylcholine (ACh) and choline (Ch) in the
      cerebrospinal fluid (CSF) of patients with Alzheimer type dementia (ATD) in
      comparison with controls. The ACh concentration was reduced significantly and
      remarkably (73%, P < 0.0002) in ATD patients and had a significant positive
      correlation with dementia scale scores (r = 0.82, P < 0.05). The Ch concentration
      was unaltered in ATD patients. These results suggest that the progressive
      reduction in ACh in the ATD brain may be reflected in its concentrations in the
      CSF.

PMID- 7824165
TI  - Norepinephrine excitation of cutaneous nociceptors in adjuvant-induced inflamed
      rats does not depend on sympathetic neurons.
AB  - To test the contribution of sympathetic postganglionic neurons (SPGNs) to
      adrenergic excitation of cutaneous nociceptor activities in adjuvant-inflamed
      rats (AI rats), we studied the effects of norepinephrine (NE) in a group of
      sympathectomized AI rats. Sympathectomy was complete in 4-6 weeks by guanethidine
      (30-50 mg/kg). NE excited polymodal receptor units in the saphenous nerve at an
      incidence (25-30%) similar to that in AI rats, while CH-38083 blocked such
      excitation. These results show that alpha 2-adrenoceptors in SPGNs are not
      involved in the norepinephrine excitation of cutaneous nociceptors in AI rats.

PMID- 7824167
TI  - Adenosine suppresses excitatory glutamatergic inputs to rat hypoglossal
      motoneurons in vitro.
AB  - Short-latency excitatory postsynaptic potentials (EPSPs), evoked by electrical
      stimulation lateral to the hypoglossal motor nucleus, were recorded from rat
      hypoglossal motoneurons (HMs) in brainstem slices. EPSPs were markedly suppressed
      or abolished by kynurenic acid (1 mM), showing that they were glutamatergic. The
      adenosine receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA, 100 nM)
      reduced EPSP amplitude to 42% of control, while the agonist 2-chloroadenosine (2
      CA, 0.5-50 microM) caused a dose-dependent reduction of the EPSP. The adenosine
      receptor antagonist 8-cyclopentyl-1, 3-dipropylxanthine (DPCPX, 0.1-1 microM)
      increased the EPSP amplitude to 124% of control, and blocked EPSP reduction by
      CCPA or 2-CA. CCPA, 2-CA and DPCPX did not significantly alter HM input
      resistance or membrane potential. These data indicate that excitatory
      glutamatergic inputs to rat HMs are modulated by adenosine A1 receptors, most
      probably at a presynaptic site. This modulation may be especially significant in
      hypoxic responses of HMs.

PMID- 7824168
TI  - Effects of electroconvulsive shock on the levels of hsp70 and hsc73 mRNA in the
      rat brain.
AB  - We evaluated the effects of electroconvulsive shock (ECS) on the expression of
      two genes encoding 70 kDa stress proteins, in the rat brain. The study was
      carried out by in situ hybridization using oligonucleotide probes specific for
      either the constitutively expressed hsc73, or the strictly inducible hsp70 gene.
      Rats were submitted to single or repeated (7 days, one session for each day)
      sessions of Electroconvulsive Shock. Animals were sacrificed at various time
      after treatment. ECS enhanced the basal expression of hsc73 in limbic areas, such
      as dentate gyrus, CA3, and median habenular nucleus. ECS induced hsp70 mRNA,
      which was not detectable in control animals, specifically in the Dentate Gyrus.
      The effect was present 2 h following treatment. Both single and repeated ECS were
      similarly effective. The finding likely reflects neuroadaptive local changes
      associated with a generalized seizure activity.

PMID- 7824169
TI  - Localization of protein kinase C subspecies in the rabbit retina.
AB  - The localization of PKC subspecies alpha, beta, gamma, epsilon and zeta was
      studied immunocytochemically in the rabbit retina. Conventional, Ca(2+)-sensitive
      PKC subtypes alpha, beta, gamma were all localized in different neuronal
      populations. The zeta-subspecies, which does not require Ca2+ for activation, was
      colocalized with PKC-alpha. PKC-epsilon, which is independent of Ca2+ and DAG,
      was colocalized with PKC-beta. Some populations of neurons, including cone
      bipolar cells, contained none of the PKC-subspecies studied. These results imply
      a cellular segregation of different signaling pathways in mammalian retina.

PMID- 7824170
TI  - Transforming growth factor-beta-2 (TGF-beta 2) is associated with mature rat
      neuromuscular junctions.
AB  - The localisation of transforming growth factor-beta-2 (TGF-beta 2) in skeletal
      muscles was investigated with immunohistochemistry. In neonates, TGF-beta 2 was
      distributed throughout the muscle fibres but as the fibres matured TGF-beta 2
      became restricted to the circumference of a small subpopulation of nuclei. These
      nuclei were judged to be the subsynaptic nuclei as they lay beneath the
      plasmalemma and were associated with alpha-bungarotoxin-labelled neuromuscular
      junctions. These observations point to TGF-beta 2 being either a trophic factor
      for mature motoneurones or an autocrine regulator of synaptic protein production.

PMID- 7824171
TI  - Effects of SK&F 96365, an inhibitor of receptor-mediated Ca2+ entry, on Ca2+
      influx and catecholamine secretion in bovine adrenal chromaffin cells.
AB  - SK&F 96365 (1-[3-(4-methoxyphenyl)propoxyl]-1-(4-methoxyphenyl)ethyl-1H-
      imidazole HCl) (1-50 microM), an inhibitor of receptor-mediated Ca2+ entry,
      reduced both acetylcholine (ACh)- and 56 mM K+ (high K+)-induced 45Ca2+ influxes
      and catecholamine secretion in bovine adrenal chromaffin cells. However, SK&F
      96365 at lower concentrations (1-3 microM) inhibited only ACh-induced 45Ca2+
      influx and secretion but not their high K(+)-induction. In Na(+)-free medium, ACh
      induced 45Ca2+ influx and secretion were also considerably decreased by SK&F
      96365 at low concentrations (1-3 microM). These results suggest that in the
      chromaffin cells, not only voltage-sensitive calcium channels but also ACh
      receptor-operated calcium channels at least in part contribute to the influx of
      Ca2+ which triggers the catecholamine secretion from the cells when the cells are
      exposed by ACh.

PMID- 7824172
TI  - Ischemic tolerance can be induced repeatedly in the gerbil hippocampal neurons.
AB  - We investigated whether ischemic tolerance can be induced repeatedly in the
      gerbil hippocampal neurons. The gerbils were firstly treated with two episodes of
      2-min forebrain ischemia 1 day apart, which procedure is known to induce ischemic
      tolerance. After 4 weeks of recirculation, the animals were subjected to a 2-min
      period of preconditioning ischemia again and then to a 3-min period of ischemia
      after 3 days. The hippocampal CA1 neurons were destroyed 7 days after 3-min
      ischemia without the second preconditioning but not in animals with the second
      preconditioning. Thus, ischemic tolerance can be induced repeatedly when the
      first ischemic tolerance has disappeared.

PMID- 7824173
TI  - Human cortical neuronal (HCN) cell lines: a model for amyloid beta neurotoxicity.
AB  - Human cortical neuronal cell lines HCN-1A and HCN-2 are killed for following
      exposure of the differentiated cells to amyloid beta-peptide(1-40), a component
      of senile plaques and other amyloid deposits in brains from Alzheimer's patients.
      We present a model of A beta toxicity uncomplicated by the presence of other cell
      types that can be used to address the mechanism of A beta neurotoxicity. This
      model will be useful in the evaluation of neuroprotective compounds which may
      attenuate cortical neuronal loss in Alzheimer's disease.

PMID- 7824174
TI  - Nitrosyl hemoglobin production during reperfusion after focal cerebral ischemia
      in rats.
AB  - We first detected a definite nitrosyl hemoglobin (HbNO) signal in the jugular
      blood by electron spin resonance spectroscopy during early reperfusion after
      cerebral ischemia. A distinct three-line hyperfine structure, characteristic to
      HbNO, was demonstrated at 30 min of recirculation after 2 h of middle cerebral
      artery occlusion in rats. Only a weak HbNO signal was observed in animals with 2
      h sustained ischemia or with sham operation. The present findings suggest that
      reperfusion after cerebral ischemia facilitates nitric oxide generation in the
      brain, which leads to the increased nitrosylation of erythrocyte hemoglobin in
      the cerebral circulating blood.

PMID- 7824175
TI  - Demonstration of CRP immunoreactivity in brains of Alzheimer's disease:
      immunohistochemical study using formic acid pretreatment of tissue sections.
AB  - C-reactive protein (CRP) is a well-known serum protein which increases during
      inflammation and deposits in damaged tissues. To establish whether CRP appears in
      brain of Alzheimer's disease (AD), we immunohistochemically investigated tissue
      sections which were pretreated with formic acid. Positive immunostaining by anti
      CRP antibodies was clearly recognized in senile plaques (SP) in the pretreated
      tissue sections, with very weak immunostaining in non-treated sections. These
      findings may suggest that the formation process of SP includes an acute-phase
      inflammatory state.

PMID- 7824176
TI  - Analysis of transcriptional initiation and translatability of brain-derived
      neurotrophic factor mRNAs in the rat brain.
AB  - The rat brain-derived neurotrophic factor (BDNF) gene consists of four 5' exons
      linked to separate promoters and one 3' exon encoding the prepro-BDNF protein. In
      the present study, using RNase protection analysis, we show that the same major
      transcription initiation sites are used for each BDNF exon mRNA in different
      brain regions and that in addition to hippocampus and cerebral cortex, kainate
      differentially induces the expression of BDNF exon mRNAs in thalamus, cerebellum
      and striatum. The 4.2 kb transcripts, are less enriched in the polysomal fraction
      of rat brain than the shorter 1.6 kb transcripts suggesting their translational
      discrimination.

PMID- 7824177
TI  - Ammonia-induced upregulation of peripheral-type benzodiazepine receptors in
      cultured astrocytes labeled with [3H]PK 11195.
AB  - Evidence suggests that peripheral-type benzodiazepine receptors (PBRs) may play a
      role in hepatic encephalopathy (HE), a condition associated with increased levels
      of ammonia in brain. In the present study, the regulation of [3H]PK 11195-binding
      to PBRs in cultured rat astrocytes that had been previously exposed to NH4Cl was
      investigated. 24 h treatment of 21-28-day-old cultures with 2, 5 or 10 mM NH4Cl
      resulted in 25 +/- 3, 48 +/- 3 and 42 +/- 4% increase in the number of [3H]PK
      11195-binding sites, respectively. No further change in [3H]PK 11195-binding was
      observed after exposure of astrocytes to 5 mM NH4Cl for 48 or 72 h. Ammonia
      treatment did not cause any significant alteration in the affinity of [3H]PK
      11195 for PBRs. The present study demonstrates the susceptibility of the PK 11195
      binding site of PBRs in cultured astrocytes to ammonia and suggests that increase
      in brain ammonia concentration causes a supersensitivity of PBRs.

PMID- 7824178
TI  - Lack of effect of antipsychotic and antidepressant drugs on glutamate receptor
      mRNA levels in rat brains.
AB  - By employing multiprobe oligonucleotide solution hybridisation (MOSH) we have
      measured the levels of mRNA encoding the NMDA receptor subtypes (R1, R2A, R2B and
      R2C) and the non-NMDA glutamate receptor subtypes (GluR1, 2, 3, and 4) within rat
      brain following, 1-32 days of antipsychotic or antidepressant drug
      administration. The results suggest that the drugs studied do not significantly
      alter rat glutamatergic system mRNA levels when compared to controls.

PMID- 7824179
TI  - Cell surface gangliosides are involved in the control of human glioma cell
      invasion in vitro.
AB  - The involvement of cell surface gangliosides in glioma cell invasion in vitro was
      examined using the ganglioside-specific antibody A2B5 and Matrigel-coated 8
      microns porosity polycarbonate filters. Invasion of six cell lines derived from
      glial tumours of different histological grades was found to be markedly inhibited
      by A2B5 (50-96% inhibition) in a dose-dependent manner. Furthermore, exogenous
      gangliosides were found to prevent cell invasion when they were incubated with
      cells during the invasion assay. These results suggest that cell surface
      gangliosides are involved in glioma cell invasion in vitro, probably because of
      their adhesion-promoting action to basement membrane components.

PMID- 7824180
TI  - Selective regulation of dendritic MAP2 mRNA levels in hippocampal granule cells
      by nitric oxide.
AB  - Application of NMDA, or agents releasing nitric oxide (NO), onto the dendrites of
      hippocampal granule cells increased the levels of the mRNA encoding MAP2, a
      cytoskeletal component induced during periods of neurite outgrowth. Furthermore,
      local increases in the hybridisation signal in the molecular layer, representing
      dendritic MAP2 mRNA, occurred independently of changes in MAP2 mRNA levels in the
      cell body layer. The selective modulation of MAP2 mRNA in dendrites reveals a
      mechanism allowing a sustained stimulation of dendritic outgrowth to be confined
      to those regions of a neuron's dendritic arbour local to glutamate receptor
      stimulation.

PMID- 7824181
TI  - A behavioral model for peripheral neuropathy produced in rat's tail by inferior
      caudal trunk injury.
AB  - We attempted to develop an experimental animal model using rat's tail for
      understanding the mechanisms involving peripheral neuropathic pain. Under sodium
      pentobarbital anesthesia, the left inferior caudal trunk of the rat was resected
      between the S3 and S4 spinal nerves. Latencies of tail-flick induced by the
      stimulus such as warm (40 degrees C) and cold (4 degrees C) water to the tail
      were measured for the following 30 weeks. In addition, sensitivity of the tail to
      mechanical stimulation was tested with von Frey hairs on these rats. Operated
      rats showed abnormal sensitivity of the tail to normally innocuous mechanical and
      thermal (warm and cold) stimuli. We interpreted these results as signs of
      neuropathic pain following nerve injury. The present model offers several
      advantages in performing behavioral tests; (1) it is easy to apply thermal
      stimulation to the rat's tail using a water bottle; (2) it is easy to apply the
      mechanical stimulation with von Frey hairs and to localize sensitive areas in the
      tail; and (3) blind behavioral studies are possible due to the lack of deformity
      in the tail after surgery.

PMID- 7824182
TI  - PEC-60 increases dopamine but not GABA release in the dorsolateral neostriatum of
      the halothane anaesthetized rat. An in vivo microdialysis study.
AB  - The effect of striatal perfusion with the intestinal peptide PEC-60 on endogenous
      dopamine (DA) and gamma-aminobutyric acid (GABA) release in the dorsolateral
      striatum and GABA release in the globus pallidus was monitored using in vivo
      microdialysis in the halothane anaesthetized rat. The results show that PEC-60
      (100 nM) increases DA release in the dorsolateral striatum without influencing
      GABA release in the dorsolateral striatum or in the globus pallidus. In addition,
      PEC-60 failed to influence the extracellular striatal 3,4-dihydroxyphenylacetic
      acid (DOPAC) and homovanillic acid (HVA) levels. The PEC-60 induced increase in
      striatal DA was abolished by the addition of tetrodotoxin (1 microM) to the
      perfusion medium. These data suggest that PEC-60 plays a role in modulating
      striatal DA release but not DA metabolism and that this effect is primarily
      targeted on the presynaptic DA terminals of the nigrostriatal DA pathway rather
      than on the postsynaptic striatopallidal GABA projection neurons in the
      dorsolateral striatum.

PMID- 7824183
TI  - Aminooxyacetic acid striatal lesions attenuated by 1,3-butanediol and coenzyme
      Q10.
AB  - We previously showed that intrastriatal administration of aminooxyacetic acid
      (AOAA) produces striatal lesions by a secondary excitotoxic mechanism associated
      with impairment of oxidative phosphorylation. In the present study, we show that
      and the specific complex I inhibitor rotenone produces a similar neurochemical
      profile in the striatum, consistent with an effect of AOAA on energy metabolism.
      Lesions produced by AOAA were dose-dependently blocked by MK-801, with complete
      protection against GABA and substance P depletions at a dose of 3 mg/kg. AOAA
      lesions were significantly attenuated by pretreatment with either 1,3-butanediol
      or coenzyme Q10, two compounds which are thought to improve energy metabolism.
      These results provide further evidence that AOAA produces striatal excitotoxic
      lesions as a consequence of energy depletion and they suggest therapeutic
      strategies which may be useful in neurodegenerative diseases.

PMID- 7824184
TI  - The influence of plasma glucose concentrations on ischemic brain damage is a
      threshold function.
AB  - To investigate whether aggravation of damage in hyperglycemic subjects is a
      continuous function of changes in intra- and extracellular pH during ischemia or
      whether there is a threshold value, preischemic plasma glucose was varied from
      8.3-20.0 mM. 10 min forebrain ischemia was induced. The results showed that no
      animal with plasma glucose of < 13 mM developed seizures, and that all animals
      with glucose of > 16 mM died in status epilepticus. Half of the animals with
      plasma glucose in the range of 13-16 mM showed seizures and 50% of these died. In
      surviving animals, histological brain damage occurred in the hippocampal CA3
      sector, cingulate cortex, thalamic nuclei and substantia nigra, structures
      normally not injured by 10 min ischemia. The data demonstrate that there is a
      glucose threshold of 10-13 mM, above which seizures develop and additional damage
      appears, and another one (> 16 mM), above which seizures are invariably fatal.

PMID- 7824185
TI  - Monoaminergic systems activity and cellular defense mechanisms in the brainstem
      of young and aged rats subchronically exposed to manganese.
AB  - In 3- and 20-month-old male Wistar rats, levels of noradrenaline (NA), dopamine
      (DA), 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), ascorbic
      acid (AA), dehydroascorbic acid (DHAA), uric acid and glutathione (GSH) were
      determined by HPLC in the brainstem after subchronic oral exposure to MnCl2 200
      mg/kg (3-month-old) and 30-100-200 mg/kg (20-month-old). In aged rats, manganese
      (Mn) significantly decreased levels of NA, DA and GSH and increased 5-HIAA/5-HT
      ratio values and DHAA and uric acid levels. All these parameters were scarcely
      affected in young rats. In aged rats, individual total Mn doses/rat were
      inversely correlated with individual DA levels (r = -0.405) and GSH levels (r = 
      0.450). In conclusion, Mn induces changes in markers of monoaminergic systems
      activity in the brainstem of aged rats considerably greater than in young rats.
      The increase in AA oxidation and decrease in GSH levels are consistent with a Mn
      induced increase in formation of reactive oxygen species. The increase in uric
      acid levels provides evidence that one of these species might arise from the
      activity of xanthine-oxidase on uric acid precursors.

PMID- 7824186
TI  - Influence of vagal afferents in the sneeze reflex in cats.
AB  - We studied the effects of bilateral vagotomy and step pulmonary inflations (5,
      10, 15 mmHg, i.e., 0.66, 1.33, 2 kKPa) on sneeze reflex in ketamine-anaesthetized
      cats. Bilateral vagotomy lengthens the duration of preparatory inspiration and
      diminishes the amplitude of expiratory activities in sneeze. In contrast, 5 mmHg
      pulmonary inflation facilitates the sneeze. It shortens the inspiratory
      preparation and increases the frequency of sneeze attacks. At 10 mmHg pulmonary
      inflations, inspiration is inhibited and only expiratory thrust occurs. At 15
      mmHg pulmonary inflations, vagal afferent stimulations inhibit the sneeze.

PMID- 7824187
TI  - The relationship between learning performance and dopamine in the prefrontal
      cortex of the rat.
AB  - To clarify the relationship between dopamine (DA) release in the prefrontal
      cortex and learning performance, extracellular DA was measured by an in vivo
      microdialysis method during a discrimination learning task. Rats were trained to
      discriminate between lamp-on and -off states under an operant-type learning
      procedure. After stable discriminative behavior was established, a microdialysis
      experiment was conducted. Inverse relationships were seen between the relative
      ratio of DA after the beginning of a learning session to the basal level and the
      responses (total, correct and error responses) during a session. The results
      indicate that the degree of DA release in the prefrontal cortex is involve in the
      inhibitory mechanism of the response during discrimination learning performance.

PMID- 7824188
TI  - Class A basic helix-loop-helix transcription factors in early stages of chick
      neural tube development: evidence for functional redundancy.
AB  - Basic Helix-Loop-Helix (bHLH) transcription factors play essential role in
      differentiation of several cell types including neurons. We isolated chick bHLH
      transcription factor E12 cDNA and demonstrated its expression in developing
      neural tube interneurons. To examine the function of class A bHLH transcription
      factors we blocked their expression using antisense oligonucleotides.
      Simultaneous blocking of class A bHLH transcription factors in cultured neural
      tube cells results in the reduction of differentiating neurons. Blocking the
      expression of individual class A bHLH transcription factors has no detectable
      effect. These results demonstrate that class A bHLH transcription factors have a
      functional redundancy during neuronal development.

PMID- 7824189
TI  - Pan-neuronal mRNA expression of the secretory polypeptide 7B2.
AB  - The polypeptide 7B2 exhibits a widespread distribution in the CNS and in the
      endocrine tissues. By in situ hybridization in the mouse tissues, we detected 7B2
      mRNA transcripts in most, if not all, neurons of the brain and spinal cord, and
      in the cranial and spinal ganglia. 7B2-mRNA was undetectable in supportive glial
      cells, ependymal cells and endothelial cells. In embryonic tissues, 7B2-mRNA
      expression was observed at midgestation, starting on day 11. Both differentiated
      neurons and neuronal precursors have been shown to express 7B2 transcript. We
      conclude that 7B2-mRNA is a good molecular marker of developing and definitive
      neurons.

PMID- 7824190
TI  - Neuroprotective effects of riluzole on N-methyl-D-aspartate- or veratridine
      induced neurotoxicity in rat hippocampal slices.
AB  - The neuroprotective activity of riluzole has been studied on N-methyl-D-aspartate
      (NMDA)- or veratridine-induced toxicity in immature rat hippocampal slices.
      Neurodegeneration was assessed by the measurement of LDH release and histology.
      Veratridine-induced LDH release can be inhibited by 100 microM riluzole (-90% and
      by tetrodotoxin (1 microM). Riluzole markedly reduced (-59%) the NMDA-induced LDH
      release and this protective effect was confirmed by histology. Riluzole inhibited
      the NMDA-induced LDH release in the presence of tetrodotoxin. Moreover, a
      pretreatment with pertussis toxin (1 microgram/ml) abolished the effect of
      riluzole against NMDA-induced neurotoxicity. These results support the view that
      the neuroprotective properties of riluzole could be exerted via two distinct
      mechanisms of action.

PMID- 7824191
TI  - Effect of tetrodotoxin and potassium infusion on microdialysis extraction
      fraction and extracellular dopamine in the nucleus accumbens.
AB  - The effects of tetrodotoxin (TTX) and K+ perfusion on extracellular DA
      concentration (DAext) and extraction fraction (also known as relative recovery or
      Ed) were studied using a method for quantitative microdialysis under transient
      conditions. TTX administered through the microdialysis probe decreased DAext with
      no effect on Ed. Perfusion with high K+ increased DAext, with no initial effect
      on Ed. However, a decrease in Ed was observed under prolonged depolarization.
      These data provide further evidence that Ed may change over the course of drug
      administration. This method of quantitative microdialysis is a reliable means for
      measuring changes in DAext independently of possible changes in microdialysis
      probe efficiency.

PMID- 7824192
TI  - Glutamate production by cultured microglia: differences between rat and mouse,
      enhancement by lipopolysaccharide and lack effect of HIV coat protein gp120 and
      depolarizing agents.
AB  - Glutamate release from rat and mouse microglia subcultures grown in a serum-free
      medium was substantially greater in the presence than in the absence of a
      physiological concentration of glutamine (0.5 mM). Mouse microglia produced and
      released more glutamate than rat microglia. Glutamate accumulation in the medium
      increased with time and cell density, which is consistent with the virtual
      absence of glutamate reuptake. Lipopolysaccharide (LPS; 10-100 ng/ml), HIV coat
      protein gp120 (0.1-10 nM), high K+ (35 mM) or ATP (150 microM), did not affect
      glutamate release from cells maintained in serum-free medium. In the presence of
      1% dialyzed serum, however, LPS induced a dose- and time-dependent increase in
      the accumulation of glutamate in the medium, suggesting that, as in other cell
      types, serum factors are required for LPS binding to its receptors.

PMID- 7824193
TI  - Adenosinergic modulation of CA1 neuronal tolerance to glucose deprivation in
      organotypic hippocampal cultures.
AB  - Glucose deprivation produced neuronal degeneration of CA1 pyramidal neurons in
      hippocampal slice cultures. The effects of the adenosine agonist
      cyclohexyladenosine (CHA) and antagonist cyclopentylxanthine (CPX) on CA1
      neuronal loss following hypoglycemia was examined using propidium iodide
      fluorescence as an indicator of cell death. The intensity of propidium iodide
      fluorescence in hippocampal area CA1 was quantified using Optimas image analysis
      software. Following 2 or 3 h of glucose deprivation, CPX significantly enhanced
      injury in the CA1 region while CHA provided significant protection. These results
      suggest that adenosine plays an important role in endogenous neuronal protection
      during hypoglycemic injury, and also supports a role for the use of adenosine
      agonists as neuroprotective agents.

PMID- 7824194
TI  - Protective action of idebenone against excitotoxic degeneration in cultured
      cortical neurons.
AB  - The novel free radical scavenger and electron-trapping agent, idebenone, protects
      cultured cortical neurons against necrotic degeneration induced by either a brief
      exposure to N-methyl-D-aspartate (NMDA) or a prolonged exposure to kainate. As
      opposed to the NMDA receptor antagonist (+)-5-methyl-10,11-dihydro-5H
      dibenzo[a,d]- cyclohepten-5,10-imine hydrogen maleate (MK801), idebenone rescued
      cortical neurons even when applied 30 min after the NMDA pulse, suggesting that
      the drug interferes with the chain of toxic reactions triggered by an excessive
      stimulation of excitatory amino acid receptors.

PMID- 7824195
TI  - Evidence for amino acid concentration gradients between CSF and extracellular
      fluid.
AB  - A small volume in the extracellular space of the medulla in the anesthetized cat
      was perfused with cisternal cerebrospinal fluid (CSF) using a push-pull
      technique. The recovered perfusate was a mixture of pushed CSF and the
      extracellular fluid. HPLC-EC analysis showed that the concentration of some
      primary amino acids in recovered perfusate often differed from their
      concentrations in CSF. These results suggested that amino acid gradients existed
      between CSF and the extracellular space.

PMID- 7824196
TI  - Basic fibroblast growth factor-like immunoreactivity in the rat basilar artery
      with reference to co-localization with NADPH-diaphorase in the trigeminal
      ganglion.
AB  - The location of basic fibroblast growth factor (bFGF)-like immunoreactivity and
      nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase (neuronal nitric
      oxide synthase) activity in the rat basilar artery and in the trigeminal,
      sphenopalatine and superior cervical ganglia was investigated. bFGF
      immunoreactivity was seen mainly in adventitial nerve fibers of the rat basilar
      artery, but not in the endothelium. Electron microscopy of the tunica media
      showed a number of immunoreactive nerve endings in the vicinity of local smooth
      muscle cells. Among the cranial ganglia that innervate the basilar artery, only
      the trigeminal ganglion had bFGF-immunoreactivity neurons. Nerve cells and fibers
      with NADPH-diaphorase activity were detected in the basilar artery and in the
      sphenopalatine and trigeminal ganglia, and the co-localization of bFGF and NADPH
      diaphorase was noted only in the trigeminal ganglion. Furthermore, Fluro-gold
      tracing in combination with bFGF immunohistochemistry demonstrated that bFGF
      containing nerve fibers in the wall of the basilar artery arise from the
      trigeminal ganglion. These findings provide a morphological basis for the nitric
      oxide-mediated dilatation of cerebral arteries by bFGF.

PMID- 7824197
TI  - Compound group I excitatory input is differentially distributed to motoneurons of
      the human tibialis anterior.
AB  - The distribution of the compound group I excitatory input to various-sized
      motoneurones in the human tibialis anterior muscle was studied, using low
      intensity electrical stimulation of the common peroneal nerve. The stimulation
      initiated the H-reflex response in all motor units with a latency of
      approximately 40 ms (range 30-45 ms). In each experiment, the amplitude of the H
      reflex responses in a pair of simultaneously active motor units were assessed. It
      was shown that, although the stimulus intensity was identical, the amplitude of
      the H-reflex response was bigger in the motor unit with the higher recruitment
      threshold of the pair compared with the size of the reflex in the unit that had a
      relatively lower recruitment threshold. The present results are compared and
      contrasted with the findings in animals and one human study that suggested that
      the smaller-sized motoneurones receive larger group I excitatory input.

PMID- 7824199
TI  - Localization of pleiotrophin and midkine in the postnatal developing cerebellum.
AB  - We demonstrated that pleiotrophin (PTN) and midkine (MK), proteins which
      constitute a novel heparin-binding growth factor family, are expressed in the
      postnatal developing cerebellar cortex by an immunohistochemical method. The
      expression patterns of both factors were quite similar both temporally and
      spatially; the levels of protein expression reached a peak at P7, and strong
      immunoreactivities were localized primarily in the premigratory zone of the
      external granular layer, the molecular layer, and the white matter. These
      findings suggest that PTN and MK are co-localized and thereby exert synergistic
      functions in the developmental events such as the migration of granule cells and
      the process outgrowth of neurons.

PMID- 7824198
TI  - 6-Chloro-D,L-tryptophan, 4-chloro-3-hydroxyanthranilate and dexamethasone
      attenuate quinolinic acid accumulation in brain and blood following systemic
      immune activation.
AB  - Accumulations of the neurotoxin quinolinic acid (QUIN) occur in the brain and
      blood following immune activation and are attributed to increased metabolism of L
      tryptophan through the kynurenine pathway. Systemic administration of 4-chloro-3
      hydroxyanthranilate (an inhibitor of 3-hydroxyanthranilate-3,4-dioxygenase), 6
      chloro-D,L-tryptophan (a substrate of the kynurenine pathway) and dexamethasone
      (an anti-inflammatory agent) attenuated the accumulation of QUIN in the brain and
      blood following systemic pokeweed mitogen administration to mice. 6-Chloro-D,L
      tryptophan and dexamethasone also attenuated the increases in brain and lung
      indoleamine-2,3-dioxygenase activity and elevations in plasma L-kynurenine
      levels. We conclude that QUIN formation can be modified by drugs which act at
      different levels of the cascade of events that link immune stimulation to
      increased kynurenine pathway metabolism.

PMID- 7824200
TI  - Apolipoprotein E allele epsilon 4 is linked to increased deposition of the
      amyloid beta-peptide (A-beta) in cases with or without Alzheimer's disease.
AB  - To assess the significance of the association between apolipoprotein E (APOE)
      epsilon 4 allele and amyloid beta-peptide (A-beta) deposits in the brain, we
      performed APOE-genotyping and measured the density of A-beta deposits, neuritic
      plaques and neurofibrillary tangles in 27 cases from the Charles Foix clinico
      pathological prospective study. We found an increased density of A-beta deposits
      in the three cases with the epsilon 3/epsilon 4 genotype as compared-with epsilon
      3/epsilon 3 subjects. Surprisingly, one of the epsilon 3/epsilon 4 genotypes was
      a 88-year-old woman, with normal intellectual functions and very low densities of
      neuritic plaques and neurofibrillary tangles but very high densities of
      preamyloid diffuse deposits of A-beta. This observation contrasted with the
      expected association between Alzheimer's disease and APOE epsilon 4 allele.

PMID- 7824202
TI  - Glutamate-produced long-term potentiation by selective challenge of presynaptic
      neurons in rat hippocampal cultures.
AB  - Excitatory postsynaptic long-term potentiation (LTP) was observed after
      restricted glutamate or metabotropic agonist application to somata and proximal
      neurites of identified presynaptic neurons. LTP-induction in this way entailed
      delays of minutes that correlated with lengths of afferent fibres. Potentiation
      failed to occur in cells pretreated with colchicine to degrade their microtubular
      transport matrix. The results suggest fast axonal transport to be a message
      carrier in the acquisition process of LTP.

PMID- 7824201
TI  - Neuronal expression of Fos and Jun protein in the rat medulla and spinal cord
      after anoxic and hypercapnic stimulations.
AB  - After inhalation of 100% N2 (anoxia) or 8% CO2 (hypercapnia), neurons that
      express Fos protein (FOS) and/or Jun protein (JUN) were immunohistochemically
      identified in the CNS of rats anesthetized with urethane and alpha-chloralose.
      JUN-labeled cells were characteristically found in the respiration-related motor
      nuclei of the medulla and spinal cord, and in the central chemoreceptive area of
      the ventral medullary surface on which hypercapnia was more effective than
      anoxia, whereas FOS-labeled cells were dominant in the respiration-related
      sensory nuclei of the medulla on which anoxia was more effective than
      hypercapnia. The results suggest that the peripheral chemoreceptor and the
      central chemoreceptive pathways in the medulla and spinal cord may be traced by a
      combination of FOS and JUN expression methods.

PMID- 7824203
TI  - Antiischemic effects of propentofylline (HWA 285) against focal cerebral
      infarction in rats.
AB  - The effects of the xanthine derivative propentofylline (HWA 285), an inhibitor of
      adenosine transport, on ischemic brain damage have been evaluated in a model of
      permanent middle cerebral artery (MCA) occlusion in rats. During the postischemic
      survival period of 24 h, the animals were subjected to neurological and
      behavioral observations and then sacrificed to assess the extent of ischemic
      tissue damage by tetrazolium chloride. Posttreatment with propentofylline (0.01,
      0.05 or 0.1 mg/kg/min, continuous i.v. infusion) initiated 15 min following MCA
      occlusion, produced significant reductions in infarct volumes; the highest being
      the most effective (reduction by 39%; P < 0.005) and improved the neurological
      symptoms when compared with an untreated control group. In contrast to other
      antiischemic agents, such as glutamate receptor antagonists, the drug induced no
      behavioral disturbances. This study indicates that propentofylline may provide
      neuroprotective effect against ischemic brain damage following stroke without
      negative behavioral side effects.

PMID- 7824204
TI  - c-Fos induction in the rat spinal dorsal horn partially deafferented by dorsal
      rhizotomy.
AB  - The 4th and 5th segments of the lumbar (the L4 and L5) dorsal horn receive
      primary input from the sciatic receptive fields through the L4 and L5 dorsal
      roots. Noxious stimulation of the hindpaw with formalin induces c-Fos in neurons
      in superficial laminae (I and II) of these dorsal horn segments. Rhizotomy of the
      L5 dorsal root 2 days before stimulation resulted in a marked reduction in the
      number of neurons with c-Fos protein-like immunoreactivity (fos-neurons). At 3
      weeks after the L5 rhizotomy, the number of fos-neurons in laminae I and II
      significantly increased compared to that at 2 days post-rhizotomy. This result
      indicates that chronic partial deafferentation by dorsal rhizotomy increases
      responsiveness of superficial dorsal horn neurons to spared primary input.

PMID- 7824205
TI  - Pyroglutamyl peptidase II activity is not in the processes of bulbospinal
      TRHergic neurons.
AB  - Pyroglutamyl peptidase II (PPII) is a neuronal ectoenzyme involved in released
      thyrotropin-releasing hormone (TRH) inactivation. In an attempt to define if it
      is present in the pre or postsynaptic membrane, we induced neuronal degeneration
      of serotonin-TRHergic cells that project from raphe nuclei to the spinal cord. 2
      4 weeks after intracisternal injection of 5,7-dihydroxytryptamine, TRH levels
      decreased over 70% in the cervical, thoracic or lumbar regions of spinal cord. In
      contrast, no change of PPII activity was observed. Longer times after injection
      (6-8 weeks), a 59-66% increase in activity was detected in the lumbar region.
      These data suggest that PPII is not localized in these TRHergic neurons but
      probably in the target cells.

PMID- 7824206
TI  - Aluminum toxicity in rat hippocampal neurons.
AB  - A brief exposure of dissociated hippocampal culture to aluminum (AlCl3, 60 min)
      is toxic to neurons. The aluminum toxicity is independent of calcium or glutamate
      receptor activation. However, at a high concentration (1 mM), aluminum seems to
      have a protective effect.

PMID- 7824207
TI  - The distribution of omega-conotoxin MVIICnle-binding sites in rat brain measured
      by autoradiography.
AB  - An analogue of omega-conotoxin MVIIC, [125I]omega-MVIICnle, has been employed in
      an autoradiographic assay to define the distribution of binding sites in rat
      brain of this neuronal calcium channel antagonist. In comparison with N-type
      channels (labeled by [125I]omega conotoxin GVIA), omega-MVIICnle sites are much
      denser in cerebellum (molecular layer) than in forebrain. Binding in thalamus is
      also comparatively high for omega-MVIICnle. Under these conditions, [125I]omega
      MVIICnle binding to rat brain sections is not displaceable by the N-channel
      antagonist, omega-conotoxin GVIA. The calcium channel blocker [125I]omega
      conotoxin MVIICnle labels a unique set of binding sites in mammalian brain.

PMID- 7824209
TI  - Spontaneous acetylcholine release in the hippocampus exhibits a diurnal variation
      in both young and old rats.
AB  - Extracellular levels of acetylcholine (ACh) in the hippocampus were measured by
      the microdialysis method in freely moving young (3-4 months old) and old (18-24
      months old) female rats over a period of 24 h to examine the effect of aging on
      hippocampal ACh release. Hippocampal ACh release during a 24-h period exhibited a
      diurnal variation with higher levels during the dark cycle than during the light
      cycle in old rats as well as young rats. The present study suggests that a
      diurnal variation in ACh release is maintained fairly well until the rats are at
      least 24 months old.

PMID- 7824208
TI  - The plasma membrane Ca(2+)-ATPase mRNA isoform PMCA 4 is expressed at high levels
      in neurons of rat piriform cortex and neocortex.
AB  - Ca2+ transport mediated by the plasma membrane Ca(2+)-ATPase (PMCA) serves an
      important role in regulation of cytosolic-free Ca2+ in a variety of cells.
      Isoform PMCA4 mRNA distribution in rat brain was studied by in situ hybridization
      using 33P-labeled antisense oligodeoxynucleotide probes. Very high levels of
      hybridization were found in piriform cortex with high levels in amygdaloid
      nucleus and laminae 2 and 6 of cerebral cortex. Significantly lower levels were
      found in hypothalamic nuclei and very low or undetectable levels were found in
      cerebellum, habenula, olfactory bulb, thalamus, choroid plexus of the third and
      fourth ventricles and in CA1 and CA3 cells of the hippocampus. These results
      suggest that PMCA4 is not a housekeeping form of the Ca(2+)-ATPase.

PMID- 7824210
TI  - Circadian variations of amino acid content of suprachiasmatic nucleus in rats.
AB  - The suprachiasmatic nucleus (SCN) has been known as an oscillator of circadian
      rhythm and recently some reports suggested that excitatory amino acids were
      functioning in this nucleus. The purpose of this study is to measure the
      physiological amino acid content of this nucleus, to estimate the circadian
      variation in amino acids and the effect of light on amino acid content in the
      SCN. The content of aspartate, asparagine, glycine and serine tended to be lower
      in the light phase compared to the dark, but was not significant. As to the light
      effect on amino acid content of the SCN, only aspartate decreased when a light
      pulse was applied. These results suggest that aspartate is involved in the
      transmission of photic information within the SCN.

PMID- 7824211
TI  - Dental care as a core health service.

PMID- 7824212
TI  - The prevalence of dental caries in 5- and 12-year-old children resident in five
      locations of south Otago.
AB  - The dental caries experience of 5- and 12-year-old children from several
      locations in South Otago was examined following observations by the school dental
      nurses that there appeared to be differences. Differences between the locations
      were observed, but these were not statistically significant.

PMID- 7824213
TI  - Day-stay treatment for dental caries at a New Zealand hospital dental unit: a 5
      year retrospective audit.
AB  - A retrospective audit of day-stay dental treatment for children under general
      anaesthesia at a New Zealand hospital dental unit showed that demand for such
      treatment has risen. Waiting times increased substantially over the 5-year period
      of the study--only 3.4 percent of children had to wait more than 3 months for
      treatment in 1989-1990, compared with 28.4 percent in 1993-1994. The re-treatment
      rate over the 5-year period was 4.2 percent. Extractions were the most common
      treatment item provided, followed by Class I and Class II amalgam restorations. A
      change of operator and an improvement in equipment in the 1993-1994 period
      contributed to a change in the range of treatment provided, and a concomitant
      increase in Dental Benefit revenue. Regional Health Authorities need to take a
      more realistic approach to purchasing such services so that safe practice is
      encouraged. Purchasing bodies in general need to give high priority to integrated
      child health promotion initiatives so that the need for day-stay dental treatment
      under general anaesthesia is ultimately reduced.

PMID- 7824214
TI  - A combined orthodontic and orthognathic surgery approach to the treatment of
      extreme anterior open bite in an adult.
AB  - This report describes a combined orthodontic and orthognathic surgery approach to
      the treatment of open bite in an adult female. An aesthetically pleasing and
      stable result was achieved in which the Intercuspal and Retruded Contact
      Positions were coincident. The functioning occlusion exhibited bilateral canine
      rise and an absence of non-working-side interferences on lateral excursion.
      Incisal guidance with disclusion of the posterior occlusal surfaces occurred on
      protrusive function. There were no signs or symptoms of temporomandibular joint
      dysfunction before or after treatment.

PMID- 7824215
TI  - Funding for the school of dentistry.

PMID- 7824216
TI  - Implant-based treatment for the loss of a single tooth.
AB  - This article describes the authors' experience in the provision of single-tooth
      replacement by means of Branemark implant treatments. Over a 5-year period, 45
      treatments have been undertaken with a current fixture retention rate of 100
      percent. Careful planning and attention to detail in surgical, prosthodontic, and
      technical aspects have resulted in an excellent functional and aesthetic
      treatment with high acceptance by patients.

PMID- 7824217
TI  - Dental amalgam.

PMID- 7824218
TI  - Temporomandibular disorders.

PMID- 7824219
TI  - AIDS newsletter.

PMID- 7824220
TI  - Are dentists not doctors, also?

PMID- 7824221
TI  - The value of covenants not to compete.

PMID- 7824222
TI  - Mandibular infected buccal cyst: case report and review of literature.
AB  - A rare lesion of unknown etiology, the mandibular infected buccal cyst, is
      associated with the buccal surfaces of vital mandibular first molars in pediatric
      patients. The exact histogenesis is uncertain, but it is believed to be an
      odontogenic cyst of inflammatory origin. A well-documented example of this rare
      entity is presented here.

PMID- 7824223
TI  - Oral penicillin hypersensitivity. A case history.

PMID- 7824224
TI  - TMD incidence and socioeconomic standing. Eradicating the myth of the upper class
      patient.
AB  - Several studies have found temporomandibular disorders (TMD) to have greater
      incidence in upper socioeconomic groups of society. And at the present time, many
      TMD clinics do not accept Medicaid. Consequently, some patients may not receive
      care or may be under-represented in TMD studies because they cannot afford
      treatment. To date, no study has examined solely the social class distribution of
      TMD, and much controversy still surrounds the issue. The purpose of this
      investigation was to determine if TMD does have a greater incidence in upper and
      middle socioeconomic classes of society. It was found that a significant
      percentage of the TMD patient population (69 percent) are Medicaid beneficiaries.

PMID- 7824225
TI  - Term early-onset neonatal seizures: obstetric characteristics, etiologic
      classifications, and perinatal care.
AB  - OBJECTIVE: To describe obstetric characteristics and etiologic classifications
      and assess perinatal care in term neonates with early-onset seizures. METHODS: We
      performed a retrospective review of neonatal and obstetric records of neonates
      delivered at term with a diagnosis of early-onset seizures between January 1981
      and December 1992 at Long Beach Memorial Medical Center. Data regarding obstetric
      characteristics and etiologic classifications of the seizures were abstracted
      from the medical records. Lack of antepartum testing in high-risk patients,
      delayed intervention with nonreassuring antepartum or intrapartum fetal heart
      rate patterns, birth trauma, and failure to use prophylactic antibiotics or treat
      infection were the criteria used for identifying seizures that were potentially
      preventable. RESULTS: Forty term neonates had early-onset seizures out of 60,712
      live births (0.07%). These seizures were attributed to hypoxic events in 15
      neonates (37.5%), cerebral malformations in seven (17.5%), cerebral infarcts in
      seven (17.5%), intracranial hemorrhage in five (12.5%), infection in three, and
      an unknown etiology in three. Twenty-three neonates had 5-minute Apgar scores of
      7 or greater (cerebral malformations excluded). Seven of these neonates (30%) had
      cerebral infarcts. A review of all records identified nine cases (22.5%) of the
      early-onset seizures as potentially preventable. CONCLUSION: The majority of the
      term early-onset neonatal seizures identified did not appear to be preventable.
      Many of the neonates with 5-minute Apgar scores of 7 or greater had cerebral
      infarcts.

PMID- 7824226
TI  - Predicting low Apgar scores of infants weighing less than 1000 grams: the effect
      of corticosteroids.
AB  - OBJECTIVE: To evaluate maternal and neonatal factors that predict low Apgar
      scores in newborns weighing less than 1000 g. METHODS: From a data set of all
      live-born infants who were delivered between 1979-1991 and who weighed 1000 g or
      less, we reviewed the records of 837 neonates born at 24-28 weeks' gestation.
      Potential risk factors were evaluated for associations with a 1-minute Apgar
      score of 3 or less and a 5-minute Apgar score of 6 or less. Analyses used chi 2
      test and multiple logistic regression. RESULTS: The prevalence of 1-minute Apgar
      scores of 3 or less decreased from 65.9% at 24 weeks to 38.2% at 28 weeks, and
      the prevalence of 5-minute Apgar scores of 6 or less decreased from 83.3% at 24
      weeks to 51.2% at 28 weeks. As the birth weight increased from 500-599 g to 900
      1000 g, 1-minute Apgar scores of 3 or less decreased from 77.0% to 39.6%, and 5
      minute Apgar scores of 6 or less decreased from 89.2% to 56.4%. Aside from
      gestational age and birth weight, corticosteroid use was the strongest predictor
      of Apgar scores above 3 at 1 minute and above 6 at 5 minutes. Male and nonvertex
      presenting infants had an increased likelihood of low Apgar scores, as did
      infants with cord blood pH less than 7.05 or bicarbonate value less than 17
      mEq/L. CONCLUSION: Neonates at very low gestational ages and birth weights are
      more likely than larger or more mature infants to have low Apgar scores. Males,
      nonvertex-presenting infants, and those who are acidotic at birth also have an
      increased prevalence of low scores. Infants born to mothers treated with
      antenatal corticosteroids are less likely to have low Apgar scores. This finding
      indicates that antenatal corticosteroids may benefit the newborn at birth, before
      respiratory distress syndrome becomes apparent.

PMID- 7824227
TI  - Fetal growth and the etiology of preterm delivery.
AB  - OBJECTIVE: To confirm that preterm delivery is associated with fetal growth
      restriction (FGR), and to determine if the various etiologies of preterm delivery
      are associated with the same degree and type of FGR. METHODS: Two hundred ninety
      young, primarily minority gravidas who had routine initial ultrasound
      examinations also had subsequent ultrasound examinations at 32 weeks' gestation.
      Fetal growth characteristics were compared between preterm (less than 37 weeks'
      gestation) and term deliveries, and among preterm deliveries with medical or
      obstetric indications, premature rupture of membranes (PROM), and spontaneous
      preterm labor. RESULTS: Forty-six infants (15.9%) were born preterm. At 32 weeks'
      gestation, all fetuses later delivered preterm were already smaller than fetuses
      later delivered at term (P < .05) for all dimensions: head circumference (HC),
      abdominal circumference (AC), biparietal diameter (BPD), and femur length (FL).
      However, after stratifying by cause of preterm delivery for those fetuses later
      delivered for medical or obstetric indications, we found that only AC was
      decreased (P < .01) and that the HC-AC ratio was elevated (asymmetric FGR).
      Neonates delivered after unsuccessfully treated PROM or preterm labor were
      symmetrically smaller in all characteristics (HC, AC, BPD, and FL). CONCLUSION:
      By 32 weeks' gestation, fetuses later delivered preterm are already significantly
      smaller than fetuses later delivered at term. However, when stratified by the
      etiology of preterm delivery, infants delivered preterm for medical or obstetric
      indications had asymmetric growth patterns, which suggests a growth failure late
      in pregnancy. Infants delivered preterm after PROM or after failed or no
      tocolysis for spontaneous preterm labor were proportionately smaller, implying an
      overall slowing of growth that may originate early in pregnancy and possibly
      demonstrate a more chronic stress.

PMID- 7824228
TI  - Ultrasonographic left cardiac axis deviation: a marker for fetal anomalies.
AB  - OBJECTIVE: To determine if a relation exists between left cardiac axis deviation
      and fetal anomalies. METHODS: Estimation of cardiac axis was attempted
      prospectively as part of the cardiac examination in approximately 41,500 second-
      and third-trimester fetuses scanned between 1987-1993. Those with heart axes
      greater than 75 degrees to the left were considered to have left axis deviation.
      Only cases with postnatal follow-up were included. RESULTS: Thirty-four fetuses
      with left cardiac axis deviation had postnatal follow-up; eight were normal and
      26 abnormal (positive predictive value 76%). Twenty-one fetuses had cardiac
      abnormalities (ten of these had additional extracardiac findings), and five had
      extracardiac findings only. CONCLUSION: Although left cardiac axis deviation can
      occur as an isolated sonographic finding in an otherwise normal fetus, most cases
      will demonstrate abnormalities of cardiac and/or extracardiac anatomy. Left
      cardiac axis deviation is largely associated with cardiac abnormalities,
      especially conotruncal anomalies, which may not be detectable by a four-chamber
      view alone. Therefore, the cardiac axis should be examined routinely as part of
      the four-chamber view of the fetal heart.

PMID- 7824229
TI  - The relationship between maternal and neonatal anthropometric measurements in
      term newborns.
AB  - OBJECTIVE: To determine whether measures of maternal lean mass, fat reserves, or
      a combination of both best predict the various measures of newborn size at birth.
      METHODS: The population consisted of 1205 multiparous, predominantly black women
      at high risk for fetal growth retardation, who delivered at term at the
      University of Alabama at Birmingham. Maternal body mass index (BMI) was
      calculated using the reported pre-pregnancy weight. Maternal anthropometric
      measurements taken at mid-pregnancy included skinfold thicknesses, lean body
      mass, and mid-arm, calf, and wrist circumferences. Weight and 11 other neonatal
      measurements were made within 24 hours of birth and related to various maternal
      anthropometric measurements. RESULTS: Reported maternal pre-pregnancy weight was
      the best predictor of all neonatal size measures except for the neonatal skinfold
      thicknesses, which were better predicted by the pre-pregnancy BMI. For example,
      the range between the tenth and 90th percentiles of maternal pre-pregnancy weight
      (46.3-86.4 kg) was associated with 295 g birth weight compared to only 188 g
      birth weight for a measure of lean body mass. CONCLUSION: Most maternal
      anthropometric measurements were significantly associated with most neonatal
      measurements. However, for nearly every neonatal measurement considered, the
      maternal pre-pregnancy weight was the best predictor.

PMID- 7824230
TI  - The role of endocervical curettage at cervical conization for high-grade
      dysplasia.
AB  - OBJECTIVE: To quantify the risk of invasive cancer above the location where the
      conization specimen was taken in patients with an endocervical curettage (ECC)
      positive for dysplasia at conization for high-grade cervical intraepithelial
      neoplasia (CIN), and to determine if any pathologic features may influence this
      risk. METHODS: The charts of 104 patients who underwent cervical conization for
      high-grade dysplasia followed by repeat conization or hysterectomy at Los Angeles
      County + University of Southern California Women's Hospital between January 1986
      and December 1992 were reviewed retrospectively. Patients with invasive cancer or
      glandular dysplasia on the initial conization were excluded. The ECC performed
      immediately after conization biopsy (conization ECC) was benign in 63 patients
      and contained dysplasia in 41. All available conization ECC specimens that
      contained dysplasia were evaluated for volume of dysplasia and degree of
      cytologic atypia. Fisher exact test was used for statistical comparison between
      and within groups. RESULTS: Invasive cancer was not present in any patients in
      the benign ECC group but was present in nine (22%) patients in the dysplasia
      group (P < .0001); five of these patients had microinvasion (no more than 3 mm of
      stromal invasion and no lymph-vascular space involvement) and four had frank
      invasion. Comparison of patients with involved endocervical margins revealed that
      none of 37 patients in the benign ECC group versus eight of 27 patients in the
      dysplasia group had invasive cancer (P < .0005). All patients with invasion were
      35 years or older and all patients with frank invasion were 50 years or older.
      Neither volume nor cytologic grade of dysplasia in the ECC was predictive of
      invasion in the residual cervix. CONCLUSIONS: An ECC at conization positive for
      dysplasia is an important predictor of invasion in the residual cervix of
      patients whose conization reveals high-grade intraepithelial neoplasia and should
      be routinely performed. Women 50 years or older with both a positive endocervical
      margin and conization ECC should undergo repeat conization before further
      therapy. Women under 50 years of age should undergo repeat conization if
      fertility is not desired; otherwise, close follow-up is necessary to exclude the
      presence of an invasive lesion in the residual cervix.

PMID- 7824231
TI  - Comparison of management algorithms for the evaluation of women with low-grade
      cytologic abnormalities.
AB  - OBJECTIVE: To present our clinical experience using a repeat Papanicolaou smear
      and human papillomavirus (HPV) DNA testing to evaluate patients with low-grade
      cytologic abnormalities. METHODS: We performed a retrospective chart review of
      women who were referred for the evaluation of a Papanicolaou smear and were
      diagnosed as having either atypical cells of undetermined clinical significance
      or a low-grade squamous intraepithelial lesion (SIL). All women included in this
      review had a repeat Papanicolaou smear, HPV DNA testing with the Hybrid Capture
      method, and a colposcopic examination. RESULTS: The sensitivity and specificity
      of the repeat Papanicolaou smear for detecting biopsy-confirmed cervical
      intraepithelial neoplasia (CIN) were 0.74 and 0.67, respectively, in the 398
      women referred for a previous low-grade SIL or atypical Papanicolaou smear. The
      sensitivity and specificity of a HPV DNA test positive for "high oncogenic risk"
      HPV types were 0.73 and 0.66, respectively. Triage using a repeat Papanicolaou
      smear and an HPV DNA test in combination correctly identified 92% of the women
      with biopsy-proven CIN, but 71% of the women would have been referred for
      colposcopy with this form of triage. CONCLUSIONS: A repeat Papanicolaou smear
      combined with a HPV DNA test is a sensitive alternative to colposcopic evaluation
      for the detection of CIN in women referred for a previous low-grade abnormal
      Papanicolaou smear. However, because of the low specificity of this approach, it
      results in only modest cost reductions compared to the more standard triage of
      performing colposcopy at the first visit.

PMID- 7824232
TI  - Diagnosis and follow-up of simple ovarian cysts detected by ultrasound in
      postmenopausal women.
AB  - OBJECTIVE: To determine the malignancy rate in ultrasound-diagnosed, anechoic,
      small, simple ovarian cysts in postmenopausal women, and to investigate the
      natural history of these cysts by ultrasound follow-up. METHODS: Eighty-three
      postmenopausal women with small, completely anechoic, thin-walled ovarian cysts
      (less than 5 cm, mean of orthogonal diameters) were diagnosed at our ultrasound
      unit during the period 1983-1992. Forty-three underwent surgery; the remaining 40
      were offered follow-up ultrasonography as part of the present study, and, of
      them, five died, two were unavailable because of intercurrent disease, and one
      moved abroad, leaving 32 to be included in our study. RESULTS: There were no
      cases of ovarian cancer in the surgery group. In the nonsurgery (follow-up)
      group, the time since detection of the lesion ranged from 1-9 years. On follow-up
      ultrasonography, 12 of the 32 cysts had disappeared and only one had increased in
      size. According to histopathology records, no ovarian cancer was diagnosed in any
      of the seven cases in which the patient was not available for reexamination by
      ultrasound. CONCLUSION: Nonpalpable ovarian cysts are commonly detected by
      ultrasound in asymptomatic women, but the risk of malignancy appears to be very
      low. We recommend ultrasound follow-up of stationary lesions and that surgery be
      confined to symptomatic cases or those in which there is a family history of
      ovarian, breast, or colon cancer.

PMID- 7824233
TI  - Clinical presentation of gynecologic infections among Indian women.
AB  - OBJECTIVE: To study the clinical presentation of different gynecologic infections
      among Indian women. METHODS: This was a cross-sectional study of 257 women that
      included clinical, cytologic, colposcopic, and microbiologic screening for
      various gynecologic infections. RESULTS: Human papillomavirus (HPV) was the
      leading infection, affecting 127 (49.4%) women; however, overt warts were only
      seen in seven (2.7%) patients. Women infected with HPV had a 60.3-fold higher
      risk of developing a bleeding ectopia compared to those with other infections;
      women with an unhealthy cervix and cervical ectopias also had an increased risk
      of HPV infection (7.6- and 2.8-fold, respectively). Bacterial vaginosis, detected
      in 33.5% of the women studied, had an increased risk of bleeding ectopia (9.3
      fold), cervical ectopia (3.1-fold), cervicitis (2.9-fold), vaginitis (6.9-fold),
      and cervical hypertrophy (2.1-fold). Chlamydial infection, detected in 23.3% of
      the patient population, was associated with an eightfold increase in the risk of
      an unhealthy cervix and a fourfold increase in risk of a hypertrophied cervix.
      Immunoglobulin-A antibodies to the herpes simplex virus were detected in 53
      (20.6%) women. More than half (55.2%) of the women had two or more infections,
      and the mean delay of seeking medical treatment was 7-13 months. CONCLUSION: The
      specific finding of bleeding cervices was associated with HPV and bacterial
      vaginosis, hypertrophied cervices with chlamydia and bacterial vaginosis, and
      unhealthy cervices with chlamydia and HPV infections.

PMID- 7824234
TI  - Perineal ultrasound for evaluating the bladder neck in urinary stress
      incontinence.
AB  - OBJECTIVE: To assess the reproducibility of a new method for evaluation of the
      bladder neck with perineal ultrasound and to compare it with lateral chain
      urethrocystography. METHODS: In the first phase, two investigators examined 40
      patients using perineal ultrasound to assess the reproducibility of a new
      measurement method for the determination of the bladder neck position. In the
      second phase, 60 patients were evaluated by perineal ultrasound and lateral chain
      urethrocystography. RESULTS: With perineal ultrasound, there was good
      interexaminer agreement for determining bladder neck position, funneling, and
      bladder neck descent at rest and during the Valsalva maneuver, but not for the
      posterior angle beta during straining. Comparison of sonographic and x-ray
      assessments showed good agreement for the bladder neck position at rest, but not
      during Valsalva, whereas the posterior angle, funneling, and bladder base descent
      differed between the two techniques at rest as well as during Valsalva.
      CONCLUSION: With our new method for determining the position of the bladder neck,
      perineal ultrasound is a reliable technique that allows reproducible static and
      dynamic evaluation. Lateral chain urethrocystography is superior to perineal
      ultrasound only if bladder neck funneling is the aim of the evaluation; it is
      inferior if bladder neck mobility during maximal Valsalva is being investigated.

PMID- 7824235
TI  - Genitourinary prolapse and joint hypermobility in women.
AB  - OBJECTIVE: To determine whether joint hypermobility, a clinical marker for
      connective tissue abnormalities, is associated with genital prolapse. METHODS:
      One hundred seven women were recruited from a university gynecology clinic.
      Subjects were examined in the standing and nonstraining positions for cystocele,
      rectocele, and uterine or vault prolapse. The degree of prolapse was graded 0-3.
      A separate investigator, blinded to the results of the gynecologic examination
      and using accepted criteria, evaluated each subject for joint hypermobility.
      RESULTS: Clinical joint hypermobility was found in 39 of 107 (36%) study
      patients. Subjects with joint hypermobility had a significantly higher prevalence
      of cystocele (33 of 37 [89%] versus 40 of 69 [58%], P = .001), rectocele (32 of
      38 [84%] versus 33 of 69 [48%], P = .0002), and uterine or vault prolapse (25 of
      38 [66%] versus 20 of 69 [29%], P = .0002) compared to women with normal joint
      mobility, respectively. No differences in the prevalence of stress incontinence
      were found between the two groups. CONCLUSION: Women with joint hypermobility
      have a significantly higher prevalence of genital prolapse compared to women with
      normal mobility, which suggests an underlying connective tissue abnormality as
      one etiology of pelvic relaxation.

PMID- 7824236
TI  - Increasing trends in plural births in the United States.
AB  - OBJECTIVE: To determine the nature and possible reasons for the increasing trend
      in plural births in the United States during the 1980s. METHODS: We performed a
      descriptive analysis of births in the United States for five racial and ethnic
      groups from 1980-1989, using the United States vital records natality files.
      RESULTS: The rates of twin and triplet births rose 19 and 100%, respectively,
      during the 1980s. Approximately one-fourth of the observed increases can be
      attributed to rising maternal age. The increases in twin and triplet births
      occurred mainly among more educated and older white women. CONCLUSION: The
      association of high education status with rising rates of plural births,
      independent of maternal age, suggests that the observed increase is the result of
      increasing use of fertility-stimulating therapy among a subset of the
      childbearing population.

PMID- 7824237
TI  - Perinatal outcome of broken marriage in the inner city.
AB  - OBJECTIVE: To test the hypothesis that the erosion of family structure, epidemic
      substance abuse, and increased low birth weight (LBW) rates are interrelated.
      METHODS: In this cohort study, we analyzed information coded prospectively in a
      computerized perinatal data base. Separated, divorced, and widowed mothers were
      grouped as broken marriages. The setting was a predominantly urban, indigent
      population in a tertiary care hospital. The analysis included singleton
      pregnancies of 14,896 women receiving prenatal and intrapartum care at our
      hospital from 1986-1991. The main outcome measures included LBW, prematurity,
      small for gestational age, neonatal mortality, and neonatal intensive care unit
      admissions. RESULTS: Married mothers fared better than single mothers, but risks
      for adverse perinatal outcomes for women with broken marriages were consistently
      as high or higher than for single mothers. The rate of LBW infants was 43% higher
      in the broken marriage group than in the married group. The increased frequency
      of LBW among infants born into broken marriages was attributable mainly to
      reduced growth rather than to prematurity and was associated with substance
      abuse. CONCLUSION: Our findings indicate that mothers from broken marriages are
      at relatively higher risk for LBW infants than married mothers (odds ratio 1.5).
      Broken marriage warrants emphasis as an important perinatal risk factor.

PMID- 7824238
TI  - The impact of a policy of amnioinfusion for meconium-stained amniotic fluid.
AB  - OBJECTIVE: To evaluate the impact of an amnioinfusion (AI) policy for thick or
      moderate meconium-stained amniotic fluid (AF) on neonatal outcome, specifically
      meconium-aspiration syndrome and its complications. METHODS: We reviewed maternal
      and neonatal charts of 937 vertex, singleton pregnancies complicated by moderate
      or thick meconium-stained AF during a 3-year period. The patients were divided
      into groups according to whether AI was performed. Demographic characteristics,
      risk factors, mode of delivery, pregnancy outcome, and neonatal complications,
      including meconium-aspiration syndrome, were analyzed. RESULTS: Four hundred
      forty patients (47%) received AI (AI group); 497 (53%) did not, for the following
      reasons: imminent delivery (310 patients), occult meconium (141), or emergency
      cesarean delivery (46) (no-AI group). Our study did not show any reduction in the
      incidence of 5-minute Apgar scores of 7 or less (8 versus 7%), meconium below the
      vocal cords (28 versus 29%), meconium aspiration syndrome (4.5 versus 3.8%),
      ventilation requirement (4.3 versus 2.4%), or neonatal death (0.7 versus 0.2%) in
      the AI and no-AI groups, respectively. The AI group had a higher incidence of
      fetal heart rate abnormalities in labor (48 versus 31%, P < .05), instrumental
      delivery (15 versus 8%, P < .05), cesarean delivery (28 versus 17%, P < .001),
      and endometritis (21 versus 13%, P = .004). CONCLUSIONS: With the policy of
      routine AI for moderate or thick meconium-stained AF, AI was not clinically
      feasible in 53% of the cases. We were unable to demonstrate any improvement in
      neonatal outcome in those who received AI for moderate or thick meconium.

PMID- 7824239
TI  - Analysis of carbohydrate-intolerant profiles of mothers with normal glucose
      tolerance tests and their large for gestational age neonates.
AB  - OBJECTIVE: To examine endocrine states of mothers with normal 75-g oral glucose
      tolerance tests (GTTs) who gave birth to large for gestational age (LGA) neonates
      (group I) and to examine those neonates. METHODS: We examined plasma glucose
      levels and serum immunoreactive insulin responses after the 75-g oral GTT was
      given to group I mothers (N = 34), mothers with an abnormal oral GTT who gave
      birth to LGA neonates (group II, N = 21), and those with normal oral GTTs having
      appropriate for gestational age neonates (group III, N = 173). We also examined
      the infants, checking neonatal birth weight, levels of immunoreactive insulin and
      C-peptide immunoreactivity in cord sera at birth and the lowest blood sugar level
      after birth to see if a correlation existed between them. RESULTS: Group I and II
      mothers showed higher titers in plasma glucose levels and remarkably enhanced
      ratios of 60- to 30-minute immunoreactive insulin values (immunoreactive insulin
      up-ratio) after load compared with those of group III mothers. Cord serum
      immunoreactive insulin and C-peptide immunoreactivity were significantly higher
      and the lowest blood sugar level was significantly reduced in group I and II
      neonates compared with those in group III. We observed a positive correlation
      between cord serum immunoreactive insulin, C-peptide immunoreactivity, and birth
      weight, but a negative correlation between cord serum immunoreactive insulin,
      birth weight, and the lowest blood sugar level in group I and II neonates
      (strongest tendency in group II), but not in group III neonates. CONCLUSION: All
      of the abnormal carbohydrate metabolic responses in group I mothers and neonates
      may result in the promotion of growth in LGA fetuses similar to group II, but to
      a lesser extent. Identification of group I mothers by the immunoreactive insulin
      up-ratio after oral GTT will help predict the occurrence of LGA neonates and
      their possible hypoglycemia.

PMID- 7824240
TI  - The effect of corticosteroid administration on uterine activity and preterm labor
      in high-order multiple gestations.
AB  - OBJECTIVE: To determine if corticosteroid administration causes increased
      contractions or labor in high-order multiple gestations. METHODS: Medical records
      of all triplet and quadruplet pregnancies cared for by Phoenix Perinatal
      Associates from August 1988 to January 1992 were reviewed retrospectively. Twenty
      one women were identified; 17 of them received at least one dose of
      corticosteroids for fetal lung maturation. Fifteen of the 17 had complete
      contraction data (2 hours per day before and after steroids) available for
      analysis. The mean number of contractions in the 48 hours before steroids was
      compared to the mean number of contractions in the 48 hours after the first
      steroid injection. RESULTS: There was a significant increase in contractions
      during the first monitoring session (8-16 hours after injection, P = .002), and
      the second monitoring session. There was also a statistically increased chance of
      both labor with cervical change and the need for tocolytic intervention if the
      basal contraction rate was at least 3.5 contractions per hour than if it was less
      than 3.5 contractions per hour (P < .02). CONCLUSION: Betamethasone
      administration in triplet and quadruplet births is associated with increased
      uterine contractions, preterm labor with cervical change, and preterm labor
      requiring tocolysis. There should be fewer than 3.5 contractions per hour to
      minimize the steroid effect on uterine activity.

PMID- 7824241
TI  - Puerperal seizures after post-dural puncture headache.
AB  - OBJECTIVE: To describe eight cases of postpartum women who developed seizures
      associated with post-dural puncture headache. METHODS: Between the years 1982
      1991, more than 19,000 women at our institution underwent subarachnoid analgesia
      for delivery or puerperal tubal sterilization. In eight of these women, grand mal
      seizures developed after spinal headache. RESULTS: In all eight women, typical
      post-dural puncture headaches were followed by visual disturbances that
      progressed to cortical blindness in three. These headaches and visual
      disturbances culminated in generalized tonic-clonic seizures 2-7 days after dural
      puncture. Although some of these women had transient hypertension at the time of
      seizure, none had preeclampsia. In three of the women evaluated, there was
      evidence of regional blood flow changes; two had diffuse cerebral artery
      vasospasm seen on angiography, and the third had diminished blood flow detected
      by a xenon-flow study. CONCLUSION: We propose that cerebral vasoconstriction is
      the mechanism for post-dural puncture headaches and seizures. Anatomic brain
      displacement may incite this vasospasm. This mechanism could also be the cause of
      cranial nerve palsies that have been described after dural puncture.

PMID- 7824242
TI  - Genital herpes during pregnancy: no lesions, no cesarean.
AB  - OBJECTIVE: To determine the effects at our hospital of adoption of the 1988
      guidelines recommended by ACOG for management of genital herpes infections during
      pregnancy. METHODS: Between 1984-1986, 96 pregnancies complicated by active
      genital herpes were delivered at Parkland Hospital. The outcome of these
      pregnancies were compared with 217 similar pregnancies managed after
      implementation of the 1988 ACOG herpes guidelines. RESULTS: Adoption of the 1988
      ACOG herpes guidelines resulted in a 37% decrease in the use of cesarean delivery
      for women with genital herpes infections at our hospital. Most of this decrease
      was because the new guidelines eliminated the need for a confirmatory negative
      herpes culture before permitting vaginal delivery. No neonatal herpes infections
      occurred as a result of implementing the ACOG recommendations. CONCLUSION: The
      rate of cesarean delivery for women with genital herpes infections during
      pregnancy declined significantly at our hospital as a result of the adoption of
      ACOG herpes guidelines, and there were no neonatal consequences, such as
      increased incidence of neonatal herpes simplex virus infection.

PMID- 7824243
TI  - A prospective series of unruptured ectopic pregnancies treated by tubal injection
      with hyperosmolar glucose.
AB  - OBJECTIVE: To evaluate the safety and efficacy of hyperosmolar glucose injection
      in select unruptured tubal gestations with hCG levels less than 2500 mIU/mL.
      METHODS: In this prospective series, 16 patients with an hCG titer less than 2500
      mIU/mL and an unruptured ectopic pregnancy were treated by tubal injection with
      hyperosmolar (50%) glucose. Hyperosmolar glucose was injected transabdominally
      into the antimesenteric site of the tubal pregnancy, using a 20-gauge spinal
      needle. The main outcome measures evaluated were duration of surgery, success
      rate, time to resolution, and follow-up tubal patency rates. RESULTS: Ninety-four
      percent (15) of the subjects were treated successfully with a median time to
      resolution of 24 days (range 5-78). The one treatment failure required
      methotrexate because of rising hCG titers and worsening pain 4 days after the
      patient was treated with hyperosmolar glucose. The mean (+/- standard error)
      duration of surgery was 45 +/- 6 minutes. So far, all ten patients undergoing
      postoperative hysterosalpingograms have demonstrated tubal patency in the treated
      tube. CONCLUSION: Laparoscopic injection with hyperosmolar glucose is an
      effective, systemically nontoxic alternative treatment for select unruptured
      ectopic pregnancies (hCG less than 2500 mIU/mL) that achieves tubal patency rates
      comparable to other conservative medical and surgical treatments.

PMID- 7824244
TI  - The incidence of adhesions after prior laparotomy: a laparoscopic appraisal.
AB  - OBJECTIVE: To relate the presence of intra-abdominal adhesions after laparotomy
      to the site of incision, repeat laparotomy, and the clinical indication for prior
      surgery. METHODS: Three hundred sixty women undergoing operative laparoscopy
      after a previous laparotomy were assessed for adhesions between the abdominal
      wall and the underlying omentum and bowel. Complications resulting directly from
      these adhesions were documented. RESULTS: Patients with prior midline incisions
      had significantly more adhesions (58 of 102) than those with Pfannenstiel
      incisions (70 of 258). Patients with midline incisions performed for gynecologic
      indications had significantly more adhesions (109 of 259) than all types of
      incisions performed for obstetric indications (12 of 55). The presence of
      adhesions in patients with previous obstetric surgery was not affected by the
      type of incision. Adhesions to the bowel were significantly more frequent after
      midline incisions above the umbilicus. Twenty-one women suffered direct injury to
      adherent omentum and bowel during the laparoscopic procedure. CONCLUSIONS: Intra
      abdominal adhesions between the abdominal scar and underlying viscera are a
      common consequence of laparotomy. Patients undergoing laparoscopy after a
      previous laparotomy should be considered at risk for the presence of adhesions
      between the old scar and the bowel and omentum.

PMID- 7824245
TI  - Sexual behavior in junior high school students.
AB  - OBJECTIVE: To evaluate the association between 14 demographic variables and the
      loss of virginity in a specific sample of junior high school students in Chicago.
      METHODS: Nine hundred seventy-six students in nine Chicago junior high schools,
      sixth through eighth grades, were given an anonymous behavior survey (the
      noncognitive assessment survey). Two separate logistic regression equations were
      used to determine the relative relationships of the demographic variables to self
      reported virginity loss. RESULTS: Five variables were significantly associated
      with virginity loss in both regression equations. In rank order, they were
      gender, ethnic group, pubertal status, suicidal ideation, and sibling number
      (adjusted odds ratio 13.3, 4.57, 3.38, 1.93, and 1.24, respectively). Nine
      variables did not have a consistent relation with early sexual activity: church
      attendance, religious affiliation, grade average, housing status, marital status
      of natural parents, self-esteem, sex education knowledge, school attendance, and
      chronologic age. CONCLUSIONS: These results call into question two widely held
      assumptions that form the foundation of many teen pregnancy prevention efforts.
      First, although many believe that sex education courses can affect behavior, we
      found no link, either positive or negative, between knowledge of reproductive
      biology and age of first intercourse. Second, self-esteem level was not
      associated with age of first intercourse. The variables that did seem related to
      early sexual activity do not lend themselves to easy manipulation. Our findings
      suggest that current school-based efforts to alter teen pregnancy rates and
      sexual behavior are unlikely to succeed.

PMID- 7824246
TI  - A prospective study of bone density and pregnancy after an extended period of
      lactation with bone loss.
AB  - OBJECTIVES: To determine if pregnancy after an extended period of lactation
      curtails the recovery of maternal bone mineral density. METHODS: Twenty-five
      women who fully breast-fed their infants for at least 6 months and had a
      subsequent pregnancy within 18 months of initiating lactation were studied
      longitudinally. Twenty controls breast-fed similarly, but had no subsequent
      pregnancy. The women were healthy, well-nourished, and between 20-40 years old.
      Bone mineral density was measured by dual x-ray energy absorptiometry at the
      spine and hip. RESULTS: Both cases and controls lost bone mineral density with
      extended lactation. The case group had a bone mineral density recovery comparable
      to the controls. CONCLUSION: Women with the dual calcium demands of extended
      lactation and a subsequent pregnancy are not at risk for failure of bone recovery
      to pre-lactation levels.

PMID- 7824247
TI  - Physical examination of the augmented breast: description of a displacement
      technique.
AB  - Physical examination of the augmented breast should include an evaluation of both
      the natural breast tissue and the implant. By displacing the implant with one
      hand, the other hand can palpate breast tissue separately. This technique
      facilitates breast cancer screening and can also be used to evaluate the
      symptomatic patient. The patient with breast implants presents certain unique
      physical findings.

PMID- 7824248
TI  - Using a vaginal tube to separate the uterus from the vagina during laparoscopic
      hysterectomy.
AB  - Hysterectomy performed totally by laparoscopy has few advocates because
      separating the cervix from the vagina is difficult. This technical difficulty can
      be overcome by placing a wide-bore plastic tube in the vagina to expose the
      cervico-vaginal junction and stretch the vaginal fornices. The stretched vagina
      falls away from the cervix as diathermy cuts over the tube rim. The tube guides
      the incision, and the plastic protects any adjacent structures. The most
      convenient external diameter is between 4-5 cm. Made from smooth, electrically
      inert plastic, the tube's opposite distal end has a valve that maintains the
      pneumoperitoneum. We have used it in 73 cases, and the only associated
      complication has been one vault pelvic hematoma.

PMID- 7824249
TI  - Molecular analysis of the RhD genotype in fetuses at risk for RhD hemolytic
      disease.
AB  - The objective of this study was to evaluate the accuracy of a DNA-based testing
      methodology in determining the RhD genotypes of fetuses at risk for RhD hemolytic
      disease. We designed a multiplex polymerase chain reaction-based test based on
      recent RhD and RhCE sequence information. To improve the accuracy of the results,
      two different portions of the RhD gene were examined. Deoxyribonucleic acid was
      extracted from fetal specimens, portions of the RhD gene were amplified by the
      polymerase chain reaction, and the amplified product was run on a polyacrylamide
      gel to look for the presence or absence of the RhD gene. We tested 67 amniotic
      fluid and two chorionic villus specimens to determine the fetal RhD genotype in
      pregnancies at risk for RhD hemolytic disease. Forty-seven of the 69 specimens
      were determined to be Rh-positive, and 22 were Rh-negative. Fifty of the 69 fetal
      specimens--31 Rh-positive and 19 Rh-negative--were serotyped at birth. In all 50,
      there was complete correlation between the DNA analysis and the serotyping
      results. RhD gene analysis is a rapid and reliable method that provides an
      accurate fetal genotype to aid in the prenatal care of RhD-alloimmunized women.

PMID- 7824250
TI  - The process of resident selection: a view from the residency director's desk.
AB  - In 1992, the Executive Council of the Association of American Medical Colleges
      recommended that a computerized application system be investigated. Under this
      system, the application package would include: 1) a standardized application
      form, 2) a personal statement, 3) a dean's letter, 4) transcripts, 5) a
      chairman's letter, and 6) United States Medical Licensing Examination (USMLE)
      scores. To investigate the value residency directors placed on these items, all
      directors from Accreditation Council for Graduate Medical Education--approved
      residency programs in obstetrics and gynecology and family practice residency
      programs were surveyed. The directors were asked to prioritize the usefulness of
      the proposed components of the Electronic Residency Application Service
      application package. Transcripts, the dean's letter, and USMLE scores ranked
      highest (in descending order) for the obstetrics and gynecology residency
      directors for making decisions about "inviting a student for an interview,"
      whereas the dean's letter, personal statement, and transcripts ranked highest for
      the family practice residency directors. Both ranked the interview as most
      valuable in ranking a student in the residency match. Although these two
      disciplines do not represent all fields, our study indicates that residency
      programs are not homogeneous in their value systems and that certain
      characteristics may predict those values.

PMID- 7824251
TI  - Hormone replacement therapy and endometrial cancer risk: a meta-analysis.
AB  - OBJECTIVE: To assess the association of unopposed estrogen or estrogen plus
      progestin and the risk of developing endometrial cancer or dying of that disease.
      DATA SOURCES: A literature search of English-language studies was performed using
      MEDLINE, a review of bibliographies, and consultations with experts. METHODS OF
      STUDY SELECTION: We identified 30 studies with adequate controls and risk
      estimates. DATA EXTRACTION AND SYNTHESIS: Risk estimates were extracted by two
      authors and summarized using meta-analytic methods. The summary relative risk
      (RR) was 2.3 for estrogen users compared to nonusers (95% confidence interval
      [CI] 2.1-2.5), with a much higher RR associated with prolonged duration of use
      (RR 9.5 for 10 or more years). The summary RR of endometrial cancer remained
      elevated 5 or more years after discontinuation of unopposed estrogen therapy (RR
      2.3). Interrupting estrogen for 5-7 days per month was not associated with lower
      risk than daily use. Users of unopposed conjugated estrogen had a greater
      increase in RR of developing endometrial cancer than users of synthetic
      estrogens. The risk for endometrial cancer death was elevated among unopposed
      estrogen users (RR 2.7, 95% CI 0.9-8.0). Among estrogen plus progestin users,
      cohort studies showed a decreased risk of endometrial cancer (RR 0.4), whereas
      case-control studies showed a small increase (RR 1.8). CONCLUSIONS: Endometrial
      cancer risk increases substantially with long duration of unopposed estrogen use,
      and this increased risk persists for several years after discontinuation of
      estrogen. Although not statistically significant, the risk of death from
      endometrial cancer among unopposed estrogen users is increased, similar to the
      increased risk of developing the disease. Data regarding risk for endometrial
      cancer among estrogen plus progestin users are limited and conflicting.

PMID- 7824252
TI  - Efficacy of oral beta-agonist maintenance therapy in preterm labor: a meta
      analysis.
AB  - OBJECTIVE: To analyze the available data on the efficacy of oral beta-agonist
      maintenance therapy in delaying delivery and in decreasing the incidence of
      preterm birth and its complications. DATA SOURCES: A computer search of English
      language abstracts using MEDLINE (medical subject heading terms: labor, premature
      and beta-adrenergic receptor agonist, therapeutic use) was supplemented with a
      review of the bibliographies of obstetric texts to identify randomized trials of
      oral beta-agonist maintenance therapy. METHODS OF STUDY SELECTION: Six trials
      were identified, of which four met our inclusion criteria for the meta-analysis.
      DATA EXTRACTION AND SYNTHESIS: Trials to be included in this meta-analysis
      underwent trial quality evaluation and data abstraction independently by two
      blinded investigators. An estimate of the odds ratio (OR) and risk difference was
      calculated for the dichotomous outcomes using both a random effects model and a
      fixed effects model. Continuous outcomes were pooled using a simple weighted
      average of the within-study difference in means. The pooled OR for preventing
      preterm delivery was 1.09 (95% confidence interval [CI] 0.60-1.99) and the OR for
      preventing recurrent preterm labor was 1.05 (95% CI 0.53-2.05). The pooled
      difference in the mean interval to delivery was -0.22 days (95% CI -2.5 to
      +1.99). CONCLUSIONS: The available data do not support a role for beta-agonist
      maintenance therapy after resolution of an acute episode of preterm labor in
      reducing the incidence of preterm delivery, increasing the interval to delivery,
      or reducing the incidence of recurrent preterm labor.

PMID- 7824253
TI  - Risk factors for fetal death in white, black, and Hispanic women.

PMID- 7824255
TI  - Rates and risks of ovarian cancer in subgroups of white women in the United
      States.

PMID- 7824254
TI  - An unexpected fetal outcome following a severe maternal motor vehicle accident.

PMID- 7824256
TI  - [Oncogenes and tumor suppressor genes in the signal transduction pathways of
      growth factors].
AB  - Growth factors, such as insulin, EGF, PDGF, are indispensable elements of the
      regulation of cell proliferation. In the last years signal transduction pathways
      of many growth factors have been elucidated. p21 ras, a proto-oncogene product,
      plays a central role in growth signalling. The medical importance of the
      investigation of Ras proteins comes from the fact that mutant forms of Ras genes
      were found in a number of human tumours. The review summarizes the signal
      transduction pathways of growth factors, with special respect to the connection
      of protooncogenes, tumour suppressor genes and cancer research.

PMID- 7824257
TI  - [Association between malignant hematologic diseases and cancer].
AB  - Between January 1 1983 and December 31 1993, 56 cases of association between
      malignant haematologic diseases and cancers were registered by authors. In their
      15 cases there was the first tumour the cancer, in 20 cases the haematologic
      malignancy, and simultaneous occurrences were found in 21 cases. With the
      exception of eleven patients the second malignancy was diagnosed (and as far as
      possible treated) in the life of patients. With the exception of three cases
      authors experienced the associations of one haematologic malignancy and one
      cancer. In their seven cases they suggest causal association between the
      treatment of the first disease and the development of the subsequent malignancy.

PMID- 7824258
TI  - [Cyclosporin therapy of patients with systemic lupus erythematosus].
AB  - Seven patients suffering from systemic lupus erythematosus (SLE) were treated by
      cyclosporin A (CSA) plus corticosteroids. The indications for treatment were:
      lupus nephritis refractory to treatment with corticosteroids and cyclophosphamide
      (one patient), nephrosis syndrome or lupus nephritis associated with severe
      cytopenia and refractory to corticosteroid treatment (5 patients), severe
      thrombocytopenia refractory to conventional treatments (one patient). The
      treatment for 6 months of this latter patient resulted in complete remission,
      lasting for at least 1.5 years. Patients with kidney involvement also responded
      to therapy. The response manifested within 1 month. Treatment lasted for a mean
      of 5.1 months (the treatment of one patient was interrupted after 1 month because
      of lack of cooperation). There were no side effects. CSA treatment in combination
      with corticosteroids, when properly indicated, may be beneficial in SLE.

PMID- 7824259
TI  - [CT-guided percutaneous drainage in the management of psoas abscesses].
AB  - The authors review their first experiences in Hungary with the CT guided
      percutaneous catheter treatment of psoas abscesses. Diagnostic aspiration from
      abscess was performed in one patient. Percutaneous catheter drainage of psoas
      abscess were performed in 4 patients. There were 4 patients with unilateral and 1
      patient with bilateral psoas abscess. 4 patients had tuberculous
      spondylodiscitis, 1 patient had staphylococcal vertebral osteomyelitis. One
      patient following diagnostic aspiration was successfully treated with
      antituberculoutic drugs. All patient treated with percutaneous catheter drainage
      received medical antituberculoutic or antibiotic therapy and showed excellent
      clinical and radiological results. There was no complication and there was no
      need to open surgical drainage in this series. CT guided aspiration is a valuable
      tool in the diagnosis of psoas abscesses as well as in the identification of the
      exact abscess etiology. Percutaneous drainage represents an efficient and
      attractive alternative to open surgical drainage in the treatment of psoas
      abscesses.

PMID- 7824260
TI  - [Prenatal follow-up of fetal tachyarrhythmia].
AB  - A case of fetal supraventricular tachycardia complicated by atrial flutter was
      recognized in the 26th week of gestation and was successfully treated during
      pregnancy. Cardiotocography could not generate appreciable result at such a fetal
      tachyarrhythmia. The intrauterine condition was evaluated by the examination of
      the Doppler blood flow parameters of the fetal vessels. During follow up strong
      correlation was found between the blood flow parameters, transplacental therapy
      and the cardiac function. When repeated and long lasting supraventricular
      tachycardias were observed, due to the atrial flutter, signs of centralization of
      the fetal circulation could be monitored as a sign of deteriorating peripheral
      oxygenation. Parallel to the improvement of the arrhythmia and to the reduction
      of the supraventricular tachycardia a significant correction of the circulatory
      parameters could be detected. Based on these experiences, investigation of fetal
      blood flow parameters is a useful tool in monitoring the intrauterine state of
      the tachyarrhythmic fetus. It can be concluded that in cases of prenatally
      diagnosed fetal arrhythmias further pre- and perinatal care should be done in
      appropriate equipped centers.

PMID- 7824261
TI  - [Primary endoscopy of the stomach].

PMID- 7824262
TI  - [Is lead contamination of paprika a threat to the fetus?].

PMID- 7824263
TI  - Overexpression of mos oncogene product in Swiss 3T3 cells induces apoptosis
      preferentially during S-phase.
AB  - When Swiss 3T3 cells are acutely infected with Moloney murine sarcoma virus
      containing the v-mos oncogene, 90% of the cells round up and detach from the
      monolayer (floating cells) and express high levels of v-Mos. The majority of the
      floating cells are generated between 30 and 70 h post infection when the cellular
      level of Mos reaches approximately 0.1% of the total protein. Seventy percent of
      the floating cells exclude trypan blue but are growth arrested with 2C or 4C DNA
      content, whereas the remaining floating cells with < 2C DNA content, are dead or
      dying, and show characteristic apoptotic phenotypes. The apoptotic cells are most
      likely generated from cells in S-phase since these cells are absent from the
      viable floating cell population and the percentage of cells with < 2C DNA
      approximated the expected S-phase fraction of logarithmically growing cells. In
      addition, 5'-bromo-2'-deoxyuridine-labeling studies showed that approximately 50%
      of the floating cells with typical apoptotic phenotypes were metabolically
      labelled with the drug. These analyses show that cell populations in different
      stages of the cell cycle are differently affected by high levels of v-Mos
      expression and cells in S-phase appear to be uniquely sensitive and undergo
      apoptosis.

PMID- 7824264
TI  - Growth enhancement of normal human keratinocytes by the antisense oligonucleotide
      of retinoblastoma susceptibility gene.
AB  - We have found that the growth of normal human keratinocytes, grown in serum-free
      medium, was significantly stimulated by the antisense oligonucleotide of
      retinoblastoma susceptibility gene (Rb). Normal human keratinocytes were exposed
      to phosphorothionate oligonucleotides which were complementary to translation
      initiation codon of Rb gene. The growth of keratinocytes was enhanced by the
      antisense, but not the sense, oligonucleotide of Rb gene in a dose-dependent
      manner from 1 to 10 microM. The Rb antisense oligonucleotide, however, did not
      result in any appreciable change in transcription of the gene when examined by
      reverse-transcription polymerase chain reaction (RT-PCR) analysis or in the
      protein expression and the phosphorylation pattern when examined by
      immunoprecipitation and Western blotting.

PMID- 7824265
TI  - The Microphthalmia gene product interacts with the retinoblastoma protein in
      vitro and is a target for deregulation of melanocyte-specific transcription.
AB  - Little is known of the molecular mechanisms underlying the differentiation of the
      melanocyte from the melanoblast or the progression from the melanocyte to a
      malignant melanoma. Since the adenovirus E1A products have proved a useful tool
      for understanding control of differentiation in other systems, we explored the
      possibility of using E1A as a probe for factors controlling melanocyte-specific
      gene expression and differentiation. The results obtained show that the
      adenovirus E1A 13S, but not the 12S, product can transform the highly pigmented
      and TPA-dependent melanocyte cell line melan-a. Transformation is characterised
      by a morphological change, loss of TPA-dependence, the ability to grow in soft
      agar and strikingly, loss of pigmentation which correlates with loss of
      expression of the melanocyte-specific TRP-1 and tyrosinase genes. Cotransfection
      assays demonstrated that repression of TRP-1 by E1A correlated with E1A binding
      to p105Rb and p300, with the target in the TRP-1 promoter being the M-box, and 11
      bp basic-Helix-loop-Helix (bHLH) factor-binding motif conserved between
      melanocyte-specific promoters. Consistent with the M-box acting as a target for
      E1a-mediated transcription repression, we also show that the basic-helix-loop
      helix-leucine zipper (bHLH-LZ) protein (Mi) encoded by the microphthalmia gene
      (mi), which is required for pigment cell differentiation, is a positive acting
      transcription factor which can interact with the retinoblastoma product in vitro
      and activate the TRP-1 promoter. Moreover, expression of the mi gene was reduced
      around 50-fold in the non-pigmented E1a-transformed melan-a cells compared to the
      nontransformed melan-a cell line, with ectopic expression of Mi able to prevent
      repression of the tyrosinase and TRP-1 promoters in the presence of E1A. Mi
      therefore appears to play a crucial role in melanocyte-specific gene expression.
      The parallels between repression of myogenesis and muscle cell bHLH factors, and
      Mi and melanocyte differentiation are discussed.

PMID- 7824266
TI  - A unique signal transduction from FLT tyrosine kinase, a receptor for vascular
      endothelial growth factor VEGF.
AB  - Flt-1 (fms-like tyrosine kinase-1), a receptor-type tyrosine kinase of sharing
      similar features with two other flt-family encoded proteins KDR/Flk-1 and Flt-4,
      has been recently identified as a receptor for Vascular Endothelial Growth Factor
      (VEGF) known to induce the proliferation of vascular endothelial cells. In this
      study, we demonstrate that Flt-1 encodes for a 180 kDa glycoprotein, binds VEGF
      with high affinity, undergoes autophosphorylation but does not generate any
      mitogenic response in transfected NIH3T3 fibroblasts. Interestingly, the
      immediate early gene c-myc was not induced, whereas the c-fos was induced very
      weakly in Flt-1 expressing NIH3T3 cells. A comparative analysis of the Flt-1
      signal cascade in the environment of endothelial cells with that of Flt-1
      expressing NIH3T3 cells showed that VEGF induced phosphorylation of PLC gamma and
      GAP complex on tyrosine in both type of cells. However, a strong activation of
      MAP kinases was observed only in endothelial cells. Further, different from many
      other receptor tyrosine kinases, tyrosine phosphorylation of Shc protein, an
      important adaptor for signal transduction from many receptor kinases, was very
      weak in both Flt-1-NIH3T3 cells and endothelial cells. These results suggest that
      Flt-1 kinase utilizes a unique signal transduction system in endothelial cells,
      and the activation of the Flt-1 kinase is insufficient to trigger a mitogenic
      response in NIH3T3 fibroblasts.

PMID- 7824267
TI  - Identification of soluble and membrane-bound isoforms of the murine flt3 ligand
      generated by alternative splicing of mRNAs.
AB  - We have recently described a novel hematopoietic growth factor, referred to as
      the flt3 ligand, that stimulates the proliferation of sub-populations of
      hematopoietic cells that are enriched for stem and progenitor cells. This factor
      is a transmembrane protein that undergoes proteolytic cleavage to generate a
      soluble form of the protein. We have isolated additional flt3 ligand isoforms by
      PCR that contain an extra exon and encode what are predicted to be either a
      soluble form of the ligand or a longer version of the transmembrane protein. We
      have also isolated cDNAs from murine T cell libraries that encode an isoform of
      the flt3 ligand that has an unusual C-terminus. This isoform results from a
      failure to splice out an intron during mRNA processing. The protein encoded by
      this cDNA is expressed on the cell surface, where it is biologically active.
      However, this novel isoform does not appear to give rise to a soluble form of the
      protein. Regulation of mRNA splicing is likely to control the generation of cell
      bound or soluble forms of this hematopoietic growth factor. Genetic mapping
      studies localize the gene encoding the flt3 ligand to the proximal portion of
      mouse chromosome 7 and to human chromosome 19q13.3.

PMID- 7824268
TI  - Expression of the positive regulator of cell cycle progression, cyclin D3, is
      induced during differentiation of myoblasts into quiescent myotubes.
AB  - L6 cells are committed skeletal muscle precursors which can be induced to
      differentiate into multinucleated, terminally differentiated myotubes. Upon
      differentiation, these immature skeletal myotubes enter a quiescent state and are
      unable to reenter the cell cycle. We have examined expression of a series of
      genes involved in regulation of progression through the G1/S boundary in
      undifferentiated L6 cells and during terminal differentiation of L6 myoblasts.
      While no change in the level of cyclin D1 transcript and a transient increase in
      cyclin D2 transcript were observed, a large increase in cyclin D3 expression was
      found. Immunohistochemistry demonstrated strong staining for cyclin D3 protein in
      the nuclei of the multinucleated myotubes from 4 independent myoblast cell lines;
      L6, L8, G8 and C2C12. Immunoprecipitation confirmed a greater than 20-fold
      increase in the levels of cyclin D3 protein in the differentiated L6 myotubes as
      well as its association with a number of proteins. Western assays demonstrated,
      further, that cyclin D3 was complexed with the cyclin dependent-kinases, cdk2 and
      cdk4, in differentiated L6 cells. However, while kinase activity specific for a
      GST-pRB fusion protein was seen for cyclin D3-containing complexes isolated from
      undifferentiated cells, the high levels of cyclin D3 in the differentiated
      myotubes had no associated kinase activity. These data demonstrate that cyclin D3
      may also have a function in terminally differentiated, quiescent cells. The lack
      of cyclin D3-associated kinase activity and its association with a number of
      different proteins suggest that cyclin D3 may regulate the function of other
      proteins by direct interaction with these factors.

PMID- 7824269
TI  - NDF/heregulin activates MAP kinase and p70/p85 S6 kinase during proliferation or
      differentiation of mammary epithelial cells.
AB  - Neu differentiation factors (NDF) are a novel family of polypeptide factors which
      activate sub-class I tyrosine kinase receptors. In all mammary epithelial cells
      analysed in this study, NDF activates the same signalling pathways while it
      induces different, cell-specific biological effects. In AU565 cells which are
      growth inhibited, as well as in T47D or HC11 cells which proliferate in response
      to NDF, the MAP kinase isoforms p44ERK1 and p42ERK2 and the p70/p85 S6 kinase are
      activated. NDF stimulates tyrosine phosphorylation and the in vitro kinase
      activity of ErbB-2. When PKC is activated by TPA, NDF is no longer able to
      activate ErbB-2 in T47D cells, leading to a blockage of cell proliferation.
      Activation of ErbB-2 by point mutation, or by monoclonal antibodies, also
      stimulates both the MAPK and the p70/p85 S6 kinase pathways. The same monoclonal
      antibodies can induce AU565 cell differentiation. In summary, during growth or
      differentiation of mammary epithelial cells, NDF stimulates several independent
      signalling pathways which can also be triggered by ErbB-2 stimulation alone. PKC
      activation blocks the biological effect induced by NDF through negative
      modulation of ErbB-2.

PMID- 7824270
TI  - Transforming growth factor-beta 1 inhibits cyclin D1 expression in intestinal
      epithelial cells.
AB  - Transforming growth factor-beta 1 (TGF-beta 1) inhibits most epithelial cell
      types by blocking cell cycle progression during the G1 phase. D cyclins are
      normally expressed during G1 and are regulators of G1 progression. One of the
      crucial functions of D cyclins is their ability to bind to a cyclin-dependent
      kinase (Cdk4). In mink lung epithelial cells, TGF-beta 1 inhibits Cdk4
      expression. We have measured cell cycle progression and D cyclins and Cdk4
      expression in non-transformed rat intestinal epithelial cell lines (IEC-6 and RIE
      1) after TGF-beta 1 treatment. In exponentially growing cultures, TGF-beta 1
      blocked DNA synthesis and suppressed cyclin D1 mRNA and protein expression,
      whereas the levels of cyclins D2, D3 and Cdk4 remained relatively unchanged. TGF
      beta 1 was also added to G0-synchronized IEC-6 cells after serum stimulation. TGF
      beta 1 prevention of G1 progression was associated with an inhibition of cyclin
      D1 protein expression. Cyclin D3 levels were not affected by TGF-beta 1 during G1
      traverse. Our results suggest that cyclin D/Cdk4 is a crucial target of TGF-beta
      1 and that regulation of this kinase is mediated through cyclin D1 in intestinal
      epithelial cells.

PMID- 7824271
TI  - TrkA neurogenic receptor regulates differentiation of neuroblastoma cells.
AB  - We examined events associated with neuronal differentiation of neuroblastoma cell
      line SH-SY5Y. Treatment with nerve growth factor (NGF) and aphidicolin, an
      inhibitor of DNA polymerases alpha and delta, induces terminal differentiation of
      SH-SY5Y cells. Following 3-4 days of treatment with NGF + aphidicolin, the cells
      irreversibly ceased proliferation and differentiated. There was a succession of
      events preceding differentiation. Down-regulation of c-myc was an early event
      occurring after less than 1 day of treatment with NGF + aphidicolin. Upregulation
      of the trkA and low-affinity NGF receptors (LNGFR) occurred after 3 days of NGF +
      aphidicolin treatment and required treatment with both NGF and aphidicolin. To
      test the role of TrkA in neuroblastic differentiation, we transfected SH-SY5Y
      cells with a TrkA-expression plasmid. In response to NGF in the absence of
      aphidicolin, the TrkA-transformant line ceased proliferation and irreversibly
      differentiated. SH-SY5Y cells bearing a control plasmid displayed only modest,
      reversible differentiation and did not cease cell proliferation in response to
      NGF. Hence, expression of NGF receptors is upregulated during differentiation of
      SH-SY5Y cells, and overexpression of TrkA enhances NGF-induced differentiation.

PMID- 7824272
TI  - Adenovirus 5 E1A induced differentiation of P19 embryonal carcinoma cells
      requires binding to p300.
AB  - We transfected P19 embryonal carcinoma (EC) cells with genes encoding the
      adenovirus 5 E1A products. Expression of either the 12S or 13S transcripts
      yielded P19 cells either incapable of proliferating or able to proliferate but
      having lost the characteristics of the EC cell parent. The proliferating clones
      of E1A expressing P19 cells were incapable of differentiating in response to
      retinoic acid or dimethyl sulfoxide, no longer expressed the SSEA-1 surface
      antigen characteristic of EC cells, and did express cytokeratin 55, a marker of
      epithelial tissues. We used a number of 12S E1A constructs carrying deletions in
      the first exon and found that the effects on P19 cell growth and differentiated
      properties were lost with alterations affecting either the N terminal 25 amino
      acids or the CR1 region of the E1A protein. Both regions are required to bind the
      cellular p300 protein that we showed is present in P19 cells. We conclude that
      binding of E1A to the p300 protein in P19 cells results in the loss of EC cell
      characteristics.

PMID- 7824274
TI  - scl, a gene frequently activated in human T cell leukaemia, does not induce
      lymphomas in transgenic mice.
AB  - The scl gene is implicated in human T cell acute lymphoblastic leukaemia (T-ALL)
      through its involvement in the t(1;14)(p32;q11) chromosomal translocation and,
      more frequently, as a result of a tumour-specific interstitial deletion on
      chromosome 1. The consequence of both these chromosomal alterations is
      overexpression of scl in the leukaemic cells. Despite the strong inference of a
      role in human T-ALL, scl has not yet been demonstrated to be causally involved in
      neoplastic transformation. We attempted to do this by generating transgenic mice
      in which scl expression was directed to the T cell lineage using the CD2 enhancer
      and the strong SR alpha viral promoter (CD2-scl mice). Three transgenic lines,
      all of which expressed the scl transgene at a high level, were bred and analysed.
      No alterations in T cell development were seen in the mice. Unexpectedly CD2-scl
      mice did not develop tumours, nor did the transgene enhance tumourigenesis by
      Moloney murine leukaemia virus. These findings throw into question the mechanism
      by which aberrant scl expression contributes to T cell leukaemogenesis.

PMID- 7824273
TI  - Spatial and temporal expression of the ret proto-oncogene product in embryonic,
      infant and adult rat tissues.
AB  - Immunohistochemical analysis with the anti-Ret antibody was performed to
      investigate the expression of the c-ret proto-oncogene product (c-Ret protein) in
      embryonic, infant and adult rat tissues. During embryogenesis, the c-Ret
      expression became detectable by day 11.5 in the developing peripheral and central
      nervous systems as well as in the excretory system. In the peripheral nervous
      system of the trunk, it was expressed at high levels in the enteric neuroblasts
      and the autonomic and dorsal root ganglia. c-Ret positive cells appeared in the
      mesenchyme around the foregut and the dorsal aorta at day 11.5 and formed the
      myenteric plexus of the whole embryonic gut and the sympathetic trunk at later
      stages respectively. Examination of the cranial region revealed that the c-Ret
      protein was expressed in neural crest cells migrating from rhombomere 4 at day
      11.5 and then became positive in the facial, glossopharyngeal and vagus cranial
      ganglia at day 12.5-13.5. After day 16.5 of gestation, the c-Ret expression was
      also observed in the trigeminal ganglion. In the central nervous system, the c
      Ret protein was expressed in the neuroepithelial cells of the ventral neural tube
      (day 11.5-14.5), the motor neurons of the spinal cord (day 18.5) as well as in
      the embryonic neuroretina (day 18.5). In addition to the nervous system, the c
      Ret expression was detected in the nephric duct (day 11.5), the ureteric bud (day
      13.5) and the collecting ducts of the kidney (day 16.5). After birth, neurons in
      the nervous systems mentioned above continued to express the c-Ret protein at
      variable levels while no c-Ret expression was observed in the kidney of adult
      rats. Furthermore, the c-Ret expression was found in the acinar cells of the
      salivary gland, the epithelial cells of the thymus and the follicular dendritic
      cells of the spleen and lymph node in infant and adult rats.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7824275
TI  - Intermolecular association and trans-phosphorylation of different neu-kinase
      forms permit SH2-dependent signaling and oncogenic transformation.
AB  - The neu oncogene encodes a 185 kDa receptor tyrosine kinase. A single point
      mutation (Val664-->Glu) within the p185neu transmembrane region results in higher
      efficiency of receptor dimerization, constitutive activity of tyrosine kinase and
      cellular transformation. The oncogenic potential of this mutated form of p185neu
      (termed Tneu) can be inactivated by site-directed alteration of a lysine residue
      in the conserved catalytic domain. In this report, we have utilized the physical
      and functional interaction of a full-length kinase-deficient neu protein (T757)
      and truncated kinase-active Tneu forms to determine critical protein domains for
      Tneu oligomerization and the resultant biological consequences. Analysis of
      various truncated Tneu mutants confirmed that the transmembrane region was
      crucial for p185 dimerization. Receptor association facilitates intermolecular
      phosphorylation of kinase-deficient mutant T757 by truncated kinase-active p185
      proteins, and the trans-phosphorylated kinase-deficient T757 was able to
      associate in vitro with proteins containing SH2 domains. Receptor-receptor
      interactions resulted in enhanced signal transduction potential and
      transformation of cell-lines co-expressing different neu-kinase forms. These
      studies emphasize a novel feature of protein-protein interaction and the
      functional significance of p185 dimerization, intermolecular phosphorylation and
      signaling which may result in cellular transformation.

PMID- 7824276
TI  - Modulation by copper of p53 conformation and sequence-specific DNA binding: role
      for Cu(II)/Cu(I) redox mechanism.
AB  - The tumor suppressor protein p53 is a metal-binding transcription factor whose
      conformation and function are altered by mutation in cancers. Using murine p53
      translated in vitro, we report here that concentrations of copper within the
      physiological range (< 30 microM) alter the conformation of wild-type p53 and
      inhibit sequence-specific DNA-binding. Direct binding of copper to p53 in the
      form of Cu(I) was demonstrated by Electron Spin Resonance using a purified
      recombinant protein containing residues 1-343 of murine wild-type p53 fused to E.
      coli maltose binding protein. Moreover, protection against the effect of Cu(II)
      sulfate was achieved by the Cu(I)-specific chelator bathocuproinedisulfonic acid
      but not by scavengers of reactive oxygen species, suggesting that alteration of
      p53 by copper depends upon a Cu(II)/Cu(I) redox mechanism, but does not require
      the production of reactive oxygen species. Thus copper at physiological
      concentrations can interact with wild-type p53 and affect its DNA-binding
      capacity.

PMID- 7824277
TI  - Increased mutation rate at the hprt locus accompanies microsatellite instability
      in colon cancer.
AB  - Hereditary Non-Polyposis Colon Cancer (HNPCC) tumors and some sporadic colon
      cancers acquire somatic changes in the length of microsatellite sequences. We
      hypothesized that this 'replication error' (RER) phenotype in these cancers
      reflects a more general defect which should result in hypermutability of
      expressed genes. To test this hypothesis mutations of hprt were studied in RER
      and non-RER tumor cell lines. Increased mutation rates of greater than 100-fold
      were found in RER compared to non-RER lines. Heterogeneity within the RER group
      suggests the likely existence of different classes of RER tumors. One non-RER
      cell line demonstrated a greater than 10-fold increase in mutation rate,
      suggesting that a novel mutator phenotype may exist in some non-RER tumors.

PMID- 7824278
TI  - Phosphorylation of a specific cdk site in E2F-1 affects its electrophoretic
      mobility and promotes pRB-binding in vitro.
AB  - The E2F transcription factor family participates in growth control presumably
      through transcriptional activation of genes that promote entry into S phase. E2F
      activity is believed to be controlled across the cell cycle by association with
      various cellular proteins, including the product of the retinoblastoma gene
      (pRB). We find that E2F-1 proteins are heterogeneously phosphorylated in insect
      cells, as a result of which they migrate as a doublet on SDS-polyacrylamide gels.
      This electrophoretic shift is shown to be dependent upon specific phosphorylation
      of E2F-1 on serine-375 (S375), near the pRB-binding site. Phosphorylation on S375
      also occurs in human cells. E2F-1 was most efficiently phosphorylated on this
      residue by cyclin A/cdk2 kinase, and to a lesser extent by cyclin A/cdk2,
      irrespective of the presence of the pRB-related p107 protein. Phosphorylation of
      E2F-1 on S375 greatly enhanced its affinity of pRB in vitro. These results
      suggest a novel way of regulating E2F-1 activity, namely by cell-cycle-dependent
      phosphorylation of this transcription factor.

PMID- 7824279
TI  - Expression of ril, a novel LIM domain gene, is down-regulated in Hras-transformed
      cells and restored in phenotypic revertants.
AB  - Several candidate genes involved in the maintenance of normal growth control (H
      rev) were identified by differential expression cloning on the assumption that
      they are expressed in phenotypically normal rat cells and repressed in closely
      related H-ras transformed cells. Previously the genes coding for lysyl oxidase (H
      rev142) and for an 18K-protein of unknown function (H-rev107) were recovered as
      cDNAs by subtraction cloning. Here we describe the identification and expression
      pattern of ril, a novel member of the heterogeneous group of genes encoding
      proteins with LIM/double zinc finger domains. The ril gene is expressed in normal
      fibroblasts and down-regulated in H-ras-transformed derivatives. Expression is
      restored in several independent phenotypic revertants derived from H-ras
      transformed cells. The predicted protein product of ril harbors a single LIM
      domain but lacks a homeodomain. The ril gene is highly conserved during evolution
      and is transcribed in various normal cell lines. Northern blot analysis and in
      situ hybridization studies showed that ril is expressed in meiotic spermatocytes,
      in somites of developing mice, and in a wide variety of tissues of adult mice.

PMID- 7824280
TI  - BHRF1, a viral homologue of the Bcl-2 oncogene, disturbs epithelial cell
      differentiation.
AB  - Epstein-Barr virus (EBV) is associated with tumours of both lymphoid and
      epithelial origin. Whilst a role for EBV latent genes in the development of these
      malignancies is accepted, it is also possible that viral proteins involved in EBV
      replication may influence the oncogenic process. BHRF1 is an immediate early
      protein which has homology with the Bcl-2 oncogene and can protect B cells from
      apoptosis. In vivo this protein is most abundantly expressed in the upper layers
      of oral 'hairy' leukoplakia (HL), a benign hyperparakeratotic tongue lesion which
      represents a focus EBV replication. We have transfected BHRF1 into the human
      squamous cell carcinoma line SCC12F which retains several features of normal
      keratinocytes behaviour in vitro. BHRF1 expression in these epithelial cells is
      associated with a delay in the commitment of cells to terminal differentiation,
      increased resistance to the DNA damaging drug, cis-platin and enhanced survival
      under conditions of serum deprivation. As the differentiation of epithelial cells
      is an apoptotic process, this data strongly suggests that BHRF1 expression delays
      the terminal differentiation of epithelial cells through the prevention of
      apoptosis. This effect of BHRF1, which may normally function to promote
      productive EBV infection, could contribute to the development of EBV-associated
      tumours.

PMID- 7824281
TI  - Cell proliferation and cell cycle progression are not impaired in fibroblasts and
      ES cells lacking c-Fos.
AB  - The transcription factor AP-1 is thought to play an important role in the control
      of cell proliferation, but the function of individual Fos and Jun family members
      is a largely unresolved issue. To directly analyse the function of c-Fos in the
      control of cell proliferation we have used embryonic stem (ES) cells and
      fibroblasts lacking c-Fos due to a disruption of the c-fos gene by homologous
      recombination. Our results demonstrate that proliferation of normally cycling
      cells and reentry of quiescent cells into the cell cycle following serum
      stimulation are not c-Fos-dependent and occur with similar efficiency in c-fos-/-
      and control cells. We also show that there is no compensatory overexpression or
      activation of other known Fos or Jun family members. On the contrary, the c-fos-/
      cells showed a reduced induction of fra-1 after serum stimulation which is in
      agreement with the previous identification of fra-1 as a c-Fos target gene.
      Comparison of the AP-1 binding and transactivation activities in c-fos-/- and +/+
      fibroblasts by electrophoretic mobility antibody supershift and CAT assays
      suggests that c-Fos is not a major component of AP-1 complexes in these cells. It
      is therefore conceivable that the lack of any detectable effect on cell
      proliferation in c-fos-/- cells might be due to a functional redundancy among the
      different AP-1 family members.

PMID- 7824282
TI  - Differentiation of P19 EC cells leads to differential modulation of cyclin
      dependent kinase activities and to changes in the cell cycle profile.
AB  - The retinoblastoma gene product (pRb) is essential for normal embryonic
      development. Phosphorylation of pRb by cyclin dependent kinases (cdk's) is
      believed to be crucial for the regulation of its function. In this report we have
      studied the regulation of pRb and cdk's during in vitro differentiation of P19
      embryonal carcinoma (EC) cells, as a model for early developmental processes.
      During EC cell differentiation, the synthesis of pRb is strongly induced. In
      addition, the phosphorylation state of induced pRb is modulated, yielding mainly
      underphosphorylated pRb. Concomitantly, the pRb kinases cdk2 and cdk4 are
      differentially regulated: cdk2 kinase activity is impaired, whereas cdk4 kinase
      activity is stimulated, due to an induction of cyclins D1 and D2. Furthermore,
      the DNA binding activity of E2F transcription factors is strongly impaired during
      differentiation and the number of cells in G1 is increased. Thus, P19 EC cell
      differentiation is accompanied by changes in cdk-activities, pRb regulation and
      E2F DNA-binding, resulting in the generation of cell types with an altered cell
      cycle profile.

PMID- 7824283
TI  - p53-dependent pathway of radio-induced apoptosis is altered in Fanconi anemia.
AB  - Fanconi anemia belongs to a group of human genetic diseases characterized by
      chromosomal instability, sensitivity to genotoxic agents associated to impaired
      processing of DNA lesions, cell cycle anomalies and cancer predisposition. We
      recently added to this list of distinctive features reduced production of
      interleukin 6 and overproduction of tumor necrosis factor alpha. Since growth
      factor deprivation, TNF alpha treatment or DNA damage can trigger apoptosis, we
      monitored the apoptotic response of FA cell lines. We show here that, although
      the spontaneous rate of apoptosis is slightly more elevated in FA than in normal
      cell cultures, the apoptosis induced by gamma-irradiation is drastically reduced
      in FA. Since the induction of apoptosis by radiation is a p53-dependent
      mechanism, the induction of this protein in FA cells was also examined. We found
      that the p53 protein is not radio-induced in FA cells belonging to the two
      genetic complementation groups examined (C and D), in contrast to normal cells.
      Moreover, the same impairment in p53 induction is observed after exposure to
      mitomycin C, a chemical agent for which FA cells demonstrate a specific cellular
      and chromosomal hypersensitivity, as well as after u.v.-B irradiation, an agent
      known to cause oxidative stress. These observations are in line with recent
      reports showing that at least certain cell lines from other chromosome breakage
      syndromes, such as ataxia telangiectasia and Bloom syndrome, may be also
      defective for radiation-induced increase of p53 protein. As the p53 tumor
      suppressor gene encodes a transcriptional activator whose targets include genes
      that regulate genomic stability, cellular response to DNA damage and cell cycle
      progression, we suggest that altered expression of p53 may be relevant to the FA
      phenotype.

PMID- 7824284
TI  - Identification of alternatively spliced mRNAs encoding variants of MDK1, a novel
      receptor tyrosine kinase expressed in the murine nervous system.
AB  - A novel member of the eck/eph family of receptor tyrosine kinases (RTKs), termed
      mouse developmental kinase 1 (MDK1), was identified and shown to be closely
      related to the Eek, Ehk1/Cek7, Ehk2, Cek4/Mek4/hek and Sek/Cek8 subfamily.
      Northern blot analysis revealed MDK1 mRNA transcripts of 6.8, 5.7, 4.0, 3.2 and
      2.6 kb that encode apparent splice variants. Sequence analyses of MDK1 cDNA
      clones from adult mouse brain predict the existence of at least five isoforms,
      including two truncated receptor variants lacking the kinase domain. Northern
      blot and in situ hybridization analysis indicate that in the adult mouse MDK1 RNA
      expression is restricted to brain, testes and spleen. The distinct patterns of
      MDK1 gene expression during mouse development suggest an important role in the
      formation of neuronal structures and possibly other morphogenic processes.

PMID- 7824285
TI  - [The absolute and relative abundance of imagoes of the taiga tick (Ixodidae) in
      the dark coniferous-deciduous valley forests of the northwestern spurs of the
      eastern Sayan].
AB  - Additions to the method of estimating the absolute and relative numbers of the
      pasture ticks in test areas are proposed. Additions take in attention the
      influence of ticks immigrating to the test area in dependence upon the isolation
      rate of that area. It has been stated that in the period 1987-1991 the mean
      relative number of I. persulcatus (mean tick number per 1 flag-kilometer of three
      decades) was 48, 27, 57, 29 and 38; the absolute tick number on test area (tick
      number per 1 hectare)--1590, 691, 1194, 641 and 668; the absolute tick number
      near the field station--1402, 647, 1496, 668 and 1108 respectively.

PMID- 7824286
TI  - [Ambiphrya ameiuri (Ciliophora: Peritricha): its ultrastructure and distribution
      on the body of carp fry].
AB  - The mass infection of larvae and youngsters of carp fishes with the peritrichoid
      Ambiphrya ameiuri has been recorded in natural condition in the Rybinsk water
      reservoir. The uneven localisation of ambiphyrans on the body surface has been
      observed on the hosts Blicca bjorkna and Abramis brama. Most high density of
      parasites was on the breast, back and tail fins. The morphological variability of
      ambiphyrans in dependence upon their localisation on the fish body has been
      observed. Details being significant for the taxonomy have been studied by means
      of the scan electron microscope. It has been found that the scopulae (greatly
      developed attaching organ of A. ameiuri) in cases of heavy infection cover about
      50-60% of the skin epithelium of fish larvae. In these cases the significant part
      of skin epithelium, which performs the respiratory function is excludes of the
      active oxygen supply that cause the illness and death of young fishes.

PMID- 7824287
TI  - [The host-opportunistic protozoa system. The dissemination of Pneumocystis
      infection in white rats under the influence of drug-induced and biological
      immunosuppression].
AB  - The main purpose of the present study is the investigation of relationships of
      Pneumocystis carinii with the organism of white rat Wistar, which is natural
      carrier of this parasite. The series of experiments has shown that the
      immunosuppressor Tricort-40 (corticosteroid of prolonged activity) in a short
      time reactivates the Pneumocystis infection. The parasites have been observed in
      a great number in the lungs and rarely in the liver. The reactivation and
      dissemination of the Pneumocystis infection have been achieved constantly and
      with great expression by the combined immunosuppression of rats, by the
      medicamentous immunosuppression (injection of T-40) and biological one (infection
      with amastigotes Leishmania infantum). The developing mixed-infection (with
      pneumocysts and leishmania) could be the basis for the parasitocenological
      relationships.

PMID- 7824289
TI  - [2 new species of trematodes (Trematoda: Zoogonidae) from fishes in the southern
      portion of the Indian and Pacific oceans].
AB  - Basing on materials collected from the fishes of the south part of the Indian and
      Pacific oceans, 2 new species of trematodes are described: Liliaoralis cataluphi
      gen. n., sp. n., Steganodermatoides notocanthi sp. n. The diagnosis of the new
      genus and discrimination are given. The detailed anatomo-morphological
      descriptions, illustrations and differential diagnoses are given for each of new
      species.

PMID- 7824288
TI  - [The structural characteristics of the nervous system in 2 species of trematodes
      from the Prosostomata group].
AB  - Topographic anatomy of the nervous systems of the trematodes Azygia lucii and
      Phyllodistomum angulatum was studied by the histochemical method of
      cholinesterase detection. The cholinergic part of the nervous system of A. lucii
      is represented by the brain, the ventral, dorsal and lateral longitudinal cords,
      by rather long complementary anterior branch of the ventral cord and by very
      short anterior branch of the dorsal cord. All cords are connected with numerous
      commissures. In the anterior region of the body, between the brain and the
      ventral sucker there are distributed 9 ring commissures. Behind the ventral
      sucker there has been revealed up to 18 commissures, 10 of which are ring ones.
      The regularity of the distribution of commissures is disturbed only in the region
      of the ventral sucker. The nervous system of such type can be regarded as a
      regular frequent orthogon. In Ph. angulatum has been revealed another type of the
      nervous system--an uneven orthogon. It is represented by the brain, 3 pairs of
      longitudinal nerve cords, small complementary anterior branches of ventral and
      dorsal cords, 5 ring commissure between the oral--and ventral suckers and one
      ventral commissure behind the ventral sucker. The origin of regular frequent
      orthogon in A. lucii and the irregular orthogon in Ph. angulatum is explained by
      certain morphological peculiarities of their structure; the body shape,
      musculature development and the reprodactive system localization. The
      morphological diversity being a characteristic for the trematode nervous system
      allows to relate them with Neorhabdocoela suborder Typhloplanoida.

PMID- 7824290
TI  - [A new host of Philomethroides lusiana in the Maritime Territory].
AB  - In the Maritime Territory of Russia (Far East) the fish Percottus glehni Dybowski
      was recorded for the first time as the host of the nematode Philomethroides
      lusiana (Vismanis, 1966). The parasites (young females) were localized in the
      swelling on the head of the fish.

PMID- 7824291
TI  - Gamekeeper's thumb. Early diagnosis and treatment.
AB  - Injuries to the ulnar collateral ligament complex in the thumb are common and
      require prompt attention. Early diagnosis is essential and must differentiate a
      partial ligament sprain from a complete disruption. Accurate diagnosis requires a
      precise examination and roentgenographic evaluation. Provocative maneuvers and
      stress radiographs may be necessary to delineate the extent of injury. Partial
      injuries are treated effectively by thumb spica immobilization. Complete ruptures
      require operative intervention and anatomic repair. To optimize outcome, the
      operative procedure requires meticulous technique and should result in minimal
      morbidity. Late ulnar collateral ligament reconstruction is more complicated and
      inferior to early surgical repair.

PMID- 7824292
TI  - Recurrent same-level, ipsilateral lumbar disc herniation.
AB  - An operative technique for the surgical management of the recurrent lumbar disc
      herniation is illustrated and presented. Five cases of ipsilateral, same-level,
      recurrent disc herniations are reviewed and discussed in light of the available
      literature. All patients presented with severe recurrent sciatica at variable
      times from the incident surgery. The treatment and possible factors favoring
      recurrence are discussed.

PMID- 7824293
TI  - Nonoperative management of upper thoracic spine fractures.
AB  - We attempted to determine if nonsurgical treatment could be successful in
      treating instability of upper thoracic spine fractures, which may receive some
      stabilization and splinting from the ribs. From 1966 to 1989, the records of all
      patients treated at Rancho Los Amigos Medical Center for fractures from T-1 to T
      8 were reviewed. Penetrating injuries and malignant lesions were excluded. A
      total of 118 patients were admitted during this period; 49 patients had
      nonsurgical treatment. Complications included 1 patient with neurologic
      worsening, brace-related skin necrosis in 8 cases, and deep venous thrombosis in
      12 patients. No failure of arthrodesis was noted. Rib fractures did not adversely
      affect late stability. We conclude that orthotic treatment of thoracic spine
      instability from T-1 to T-8 can be successful, especially in cases where early
      surgery is not possible.

PMID- 7824294
TI  - Traumatic tenosynovitis and extensor tendon rupture.
AB  - Extensor tenosynovitis is caused by a variety of conditions, but most commonly is
      associated with inflammatory arthritis. Extensor tenosynovitis with secondary
      tendon rupture due to occupational repetitive direct trauma to the dorsal
      compartments of the wrist and hand is reported in a woman. Tenosynovectomy and
      tendon transfer were performed to relieve pain and restore hand function.

PMID- 7824295
TI  - Expanding mass in the gluteal area of a 7-year-old child.
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 two
      pages. The final clinical and differential diagnoses are presented on the
      following page.

PMID- 7824296
TI  - Allograft-host mismatch in revision total hip replacement.
AB  - Mismatch between a structural femoral allograft and the distal host canal is a
      difficult problem in femoral reconstruction for revision of total hip
      replacement. A technique is presented that satisfactorily solves this problem and
      offers additional advantages over other allograft techniques, as illustrated in
      two cases.

PMID- 7824297
TI  - [In vitro activity of meropenem and seven other beta-lactam antibiotics against
      K.pneumoniae and enterobacteriaceae producing beta-lactamases with extended
      spectrum].
AB  - Meropenem is a broad antibacterial spectrum carbapenem with a good activity on
      betalactam resistant Gram-negative bacilli. 120 non repetitive strains isolated
      from clinical samples from 1989 to 1992 were selected: 60 K. pneumoniae, 7 E.
      coli, 2 E. aerogenes and 1 S. marcescens with extended spectrum betalactamases
      (23 CTX-1, 18 SHV-2, 5 SHV-3, 16 SHV-4, 4 SHV-5, 3 CTX-1 + SHV-4, 1 CAZ-1), 10 K.
      pneumoniae with broad spectrum TEM-1 enzyme, and 40 K. pneumoniae with only SHV-1
      chromosomal betalactamase. Determination of Minimal inhibitory concentrations
      (MIC) was done by agar dilution method for meropenem and 7 other betalactams
      (amoxicillin + clavulanic acid 2 mg/l, piperacillin + tazobactam 4 mg/l,
      cefoxitin, cefotetan, cefotaxime, ceftazidime, imipenem). All antibiotics except
      amoxicillin + clavulanic acid are active against strains with constitutive
      penicillinase. For strains with TEM-1 penicillinase, cephamycins, third
      generation cephalosporins and carbapenems are active. For strains with different
      extended spectrum betalactamases only cephamycins and carbapenems are efficious.
      There is no difference according to the period of isolation: 1989-90 or 1991-92.
      Meropenem has the best in vitro activity (MIC50 = 0.03 mg/l) for all strains
      independently of the nature of betalactamase.

PMID- 7824298
TI  - [Current status of resistance of bacteria to pefloxacin in hospital units. Cross
      resistance with ofloxacin and ciprofloxacin. Results of a multicenter study].
AB  - The antibacterial activities of pefloxacin (PEF), ofloxacin (OFL), ciprofloxacin
      (CIP) were measured by agar diffusion (5 micrograms strength disks) against 6370
      non duplicate clinical isolates collected in November 1991 in 40 hospitals from
      various areas in France. The MICs of PEF, OFL and CIP were determined by agar
      dilution against intermediate or resistant strains to one of the three
      antibiotics (inhibition zone < 16 mm for PEF, OFL, < 19 mm for CIP). In the
      Enterobacteriaceae the overall incidence of resistance to PEF (MIC > 4 mg/l) was
      8% with important variations between the different species: E. coli 2%,
      Salmonella 0%, E. cloacae 9%, K. pneumoniae 21%, P. mirabilis 13%, P. vulgaris
      3%, M. morganii 5%, Providencia 61%, S. marcescens 55%. Among S. aureus, the
      incidence of resistance was 3% for the methicillin-susceptible strains and 86%
      for the methicillin-resistant strains. The same applied to coagulase negative
      Staphylococci: methicillin-susceptible 9%, methicillin-resistant 62%. The
      frequency of the resistant strains was high among P. aeruginosa: 40% and A.
      baumanii: 83%. A high degree of correlation was observed between the MICs of PEF,
      OFL and CIP for all the bacterial species: r = 0.8 - 0.9. No major discrepancies
      were noted between the clinical categorizations of the activities of the three
      antibiotics for the different species except for P. aeruginosa: 4% of the strains
      were resistant to pefloxacin and susceptible to ciprofloxacin.

PMID- 7824299
TI  - [Comparative activity of oral beta-lactam antibiotics against fifty strains of
      Haemophilus influenzae producing a beta-lactamase according to bacterial
      inoculum].
AB  - Minimal inhibitory concentrations (MICs) of amoxycillin alone and in combination
      with 2 mg/l or 4 mg/l clavulanic acid, ampicillin alone and in combination with 4
      mg/l or 8 mg/l sulbactam, cefuroxime and cefaclor, were determined by the agar
      dilution method, with bacterial inoculum size ranging from 3 x 10(7) to 3 x 10(9)
      colony-forming units per ml. As expected, an inoculum effect was observed with
      cefaclor. In contrast, MICs of amoxycillin in combination with clavulanic acid
      did not significantly increase with the inoculum size. Ampicillin combined with
      sulbactam, and cefuroxime were less efficient at the highest bacterial
      concentration tested.

PMID- 7824300
TI  - [Antibacterial activity of clarithromycin and its hydroxylated derivative and two
      other macrolides against thirty strains of Streptococcus pneumoniae].
AB  - Macrolides are widely used in the treatment of respiratory infections. Here, the
      authors compared the activity of different 14-membered macrolides: erythromycin
      (Ery), roxithromycin (Rox), clarithromycin (Cla) and its 14-hydroxy metabolite 14
      OH clarithromycin (14-OH) against 30 strains of Streptococcus pneumoniae isolated
      at the Dupuytren hospital (Limoges, France) from upper respiratory tract sputum,
      ophthalmic sputum, blood samples and CSF. Twenty strains were susceptible to
      macrolides and 10 were resistant. Three strains from the susceptible and 7 from
      the resistant were resistant to penicillin. Furthermore, for all the macrolides
      except Rox and 14-OH, susceptibility tests were performed by the disk diffusion
      method on Mueller-Hinton agar. MICs50 of Cla and Ery were 0.06 mg/l. They were
      two-fold increased for 14-OH (0.125 mg/l) and four-fold increased for Rox (0.25
      mg/l). We noted that for 3 resistant strains, MICs of Cla were four-fold
      decreased than MICs of Ery. Ery, Cla and 14-OH had bactericidal activity against
      pneumococcus strains susceptible to these antibiotics at 4 and 8 times the MIC
      after 6 or 18 h. The difference between MIC and MBC was small (1 or 2 two-fold
      dilutions) for Ery, Rox and Cla. For 14-OH, this difference was within 2 to 4 two
      fold dilutions. The bactericidal activity is similar to that of amoxicillin and
      cefotaxim. A microdilution chequeboard technique was used against 3 strains and
      the FIC index did not show synergistic effect of combining Cla and 14-OH. The
      activity of Cla and 14-OH against 5 strains was not modified in the presence of
      50% fresh pooled human serum inactivated at 56 degrees C or not.

PMID- 7824301
TI  - [In vitro antibacterial activity of a new fluoroquinolone, fleroxacin, against
      hospital bacteria and regression curve].
AB  - Minimal inhibitory concentrations (MICs) of fleroxacin (FLE) were determined by
      agar dilution for 1261 bacterial strains isolated in 1992 in 4 university
      hospitals; in addition, antibiograms by agar diffusion were performed with 5
      micrograms disks. Activity of FLE against nalidixic acid (NAL) susceptible (S)
      Enterobacteriaceae was close to that of other fluoroquinolones (FQ) (MIC 50 and
      90: 0.12-0.25 micrograms/ml); like for other FQ, this activity was reduced
      against NAL intermediate and resistant (R) Enterobacteriaceae (4-32). MICs of FLE
      against P. aeruginosa were between 1 and 128 (8-128). FLE had also a good
      activity against NAL-S A. baumannii (0.12-0.5) but this activity is reduced
      against NAL-R Acinetobacter (64-128). FLE was highly active against Haemophilus
      (0.06-0.12), Gonococci (0.03-0.25), Meningococci (0.016-0.03) and B. catarrhalis
      (0.12-0.25). FLE showed activity close to the currently available FQ against
      methicillin susceptible Staphylococci (0.25-1); the resistant strains (32- > 128)
      are usually methicillin resistant. FLE is less effective against Enterococci (4
      128), Streptococci (8-16) and Pneumococci (4-8). The coefficient correlation of
      the regression curve is 0.93; for MIC breakpoints of 1 and 4 micrograms/ml, zone
      diameter breakpoints should be 20 and 15 mm.

PMID- 7824302
TI  - [In vitro bactericidal activity of seven antibiotics and four combinations
      against Neisseria meningitidis].
AB  - The authors studied, with a time-kill curve method, in a derived Hafiz medium
      broth the bactericidal effect of 7 antibiotics and 4 associations against N.
      meningitidis. Their results show a better bactericidal effect for penicillin G,
      ampicillin and chloramphenicol. Pefloxacin and ceftriaxon are less efficient. The
      association ampicillin + chloramphenicol in vitro shows no antagonism and has a
      good bactericidal activity at the early stages of bactericidal killing with N.
      meningitidis.

PMID- 7824303
TI  - [Electron microscopic studies of the action of erythromycin, doxycycline and
      ofloxacin on the growth cycle of Chlamydia trachomatis].
AB  - The aim of this work is to realise an ultra structural study of the action of
      antibiotics (doxycycline, erythromycin and ofloxacin) on the intracellular growth
      cycle of chlamydia. All assays were done on McCoy cells. Antibiotics were added
      to the culture medium two hours after inoculation with C. trachomatis. 24 and 48
      hours, cells were removed and treated by standard procedure for transmission
      electron microscopy. No difference between control-cells and cells treated with
      doxycycline, erythromycin (0.015 mg/l) and ofloxacin (0.15 mg/l), was observed in
      the inclusions (number and size). However 48 hours, the quantity of elementary
      bodies (E.B.) was lower in treated culture. The organisms were not
      morphologically different from those seen in untreated culture. At higher
      concentrations of doxycycline and erythromycin (0.03 mg/l - 0.06 mg/l), the
      inclusions were smaller. Reticulate bodies (RB) were each in separate inclusion
      indicating that no fission has taken place. At 48 hours, no infectious forms (EB)
      were observed. Small or large RBs appeared with an apparent normal cytoplasmic
      membrane within an inflated cell wall. With ofloxacin (0.3 - 0.6 mg/l),
      inclusions contained enlarged and sometimes empty bacterial cells. Doxycycline
      and erythromycin (0.03 mg/l) inhibit the division of RBs and there maturation to
      EBs Ofloxacin (0.3 mg/l) induces the production of large abnormal forms which may
      not be able to revert towards viable bacteria.

PMID- 7824304
TI  - [Microbiological consequences of chelation of bivalent metal cations by
      nitroxoline].
AB  - The present work deals with the physico-chemical and microbiological
      investigations made in order to explain the role of divalent cations in the
      mechanism of the action of nitroxoline (NIT), an antibiotic used in the treatment
      of uncomplicated urinary tract infections. Preliminary studies reported that
      bacteriostatic and bactericidal activities of NIT on Escherichia coli strains are
      decreased in the presence of Mg2+ and Mn2+ but not with Ca2+. A
      spectrophotometric study, conducted in order to elucidate the interaction between
      metal ions and NIT, showed the formation of drug-metal ion complexes. In
      addition, we examined the relationships between the metal ions-chelating property
      of NIT and its effects on the decrease of the mannose sensitive hemagglutination
      titer and the production of siderophores from E. coli. The results suggested that
      these antimicrobial activities of NIT would also be due to the complexation of
      metal ions by this molecule.

PMID- 7824305
TI  - [Evaluation of the extra- and intracellular activity of clarithromycin against
      Mycobacterium chelonae].
AB  - The in vitro activity of clarithromycin alone and in combination with amikacin,
      ethambutol and rifabutin was tested against twelve strains of M. chelonae
      abscessus and eight strains of M. chelonae chelonae isolated from patients.
      Extracellular activity of clarithromycin was assessed by determining MICs using
      the 1 p. cent proportion method in Middlebrook 7H11 agar media compared to the
      radiometric methodology in 7H12 broth at two pHs 6.8 and 7.4. The MICs obtained
      at pH 7.4 were 2 to 4 more dilutions lower than those obtained at pH 6.8. By both
      methods, clarithromycin appeared more active against isolates of M. chelonae
      chelonae than against isolates of M. chelonae abscessus. Clarithromycin- amikacin
      combination demonstrated the most important additive effect. The use of three
      drugs in association resulted in syngergistic effect. Studies of intracellular
      bacteria showed that the most effective bactericidal combination was
      clarithromycin amikacin and ethambutol together.

PMID- 7824306
TI  - [Post-antibiotic effect of three aminoglycosides against Klebsiella pneumoniae].
AB  - This paper introduces a new method to quantify post antibiotic effect. This
      method was applied to the study of the effect of three aminoglycosides
      antibiotics on seven strains of Klebsiella pneumoniae. The antimicrobial was
      removed by filtration, washing with peptone broth and neutralization by heparin.
      Growth curves were monitored by automated measurement of optical density with
      Urimat-ATB (bioMerieux). The inoculum fluctuation bias was eliminated with the
      help of a mathematical analysis of results. Absence of carry-over was controlled
      for each bacteria-antibiotic combination. A significant post antibiotic effect
      was observed with the three antibiotics after 2 hours exposure to a concentration
      equivalent to 2 x MIC. There was no significant difference between the 3
      aminoglycosides tested.

PMID- 7824307
TI  - [Synergism of the combination of enzymes or surfactants and a phenolic
      disinfectant on a bacterial biofilm].
AB  - Disrupting bacterial biofilms is necessary for a wide application domains such as
      reusable medical devices, or systems of pipes for water or fluids in cosmetics,
      food and chemicals industry. Bacterial cells embedded in a biofilm are less
      susceptible to disinfectants than suspended cells. This property is referable to
      the structure of the biofilm itself. The gangue of exopolymers and the thickness
      of a 5-day-old biofilm of Escherichia coli (more than 200 layers of bacteria),
      contribute to this decrease of susceptibility. The present work deals with the
      release of an Escherichia coli biofilm by the sequential action of enzymes and a
      phenolic disinfectant on the one hand, and by the sequential or simultaneous
      action of surfactants and the previous disinfectant on the other hand. The
      decrease of bacteria count per mm2 and the Scanning Electron Microscope
      observations exhibited a synergic action in every case. Nevertheless, Escherichia
      coli biofilms quickly reconstructed even after exposition to the previous
      treatment.

PMID- 7824308
TI  - [Sporocidic activity of sodium hypochlorite and peracetic acid alone or combined
      against free or fixed spores or on biofilm].
AB  - In order to assess the sporocidal activity of chlorine and peracetic acid (PAA),
      alone and in combination, against a spored biofilm, the biofilms of two species
      (Bacillus subtilis ATCC 6633 and Bacillus megaterium ATCC 8245) were formed on
      inert support (tygon). A sporulation kinetic of these bacteria in biofilm was
      established. Sporocidal properties of chlorine and PAA were compared against free
      spores, spores fixed by drying and spores in biofilm. The combination of these
      two products was also tested. Minimal sporocidal concentrations (MSC) of the two
      products towards free spores were determined (contact time 5 mn). The efficacy of
      these MSC were evaluated in terms of contact time on adhered spores and on spores
      in biofilm. Chlorine and PAA exhibited an excellent sporocidal activity. The
      combination of PAA and chlorine, tested by checkerboard micromethod, was found to
      be synergistic in case of free or adhered spores. The spored biofilm showed a
      high resistance. The combination of these two products revealed then only an
      additive effect.

PMID- 7824309
TI  - [Relationship between the level of minimal inhibitory concentrations of five
      antiseptics and the presence of qacA gene in Staphylococcus aureus].
AB  - The Polymerase Chain Reaction (PCR) was used to detect the qacA gene which
      encodes antiseptic resistance in 186 clinical isolates of Staphylococcus aureus.
      The results were compared with those obtained by MIC determination of 4
      antiseptics (benzalkonium chloride, hexamidine, chlorhexidine, acriflavine) and
      for ethidium bromide. The qacA gene was not detected among the 32 susceptible S.
      aureus strains, but was found in the 70 (85%) of the 82 S. aureus strains
      resistant to all 5 antiseptics. The gene was also detected in 70 (45%) of the 154
      remaining strains that were resistant to at least one antiseptic.

PMID- 7824310
TI  - [Rapid detection of tolerance of streptococci and enterococci to beta-lactam
      antibiotics by measurement of bacterial TPA].
AB  - The authors developed a rapid method for determination of tolerance of
      streptococci and enterococci to ampicillin by measuring the bacterial TPA. Of
      thirty three strains from blood cultures, 11 were tolerant with a MBC/MIC ratio >
      32. For these strains, the free TPA/total TPA ratio measuring the bacterial lysis
      after a 2hrs incubation with 2 MIC of ampicillin, had an average of 38% (SD = 21)
      versus 88.6% (SD = 17.9) for the non-tolerant strains. There is a good
      correlation between the values of MBC/MIC ratios and the free TPA/total TPA
      ratios. The authors concluded that TPA assessment after 2hrs incubation with
      antibiotic can predict the antibiotic tolerance of streptococci or enterococci.

PMID- 7824311
TI  - [Evaluation of the Spiral method to determine the MIC of various antibiotics].
AB  - The determination of minimal inhibitory concentrations (MICs), which is sometimes
      necessary in routine, is cumbersome. We tried to compare the Spiral gradient
      endpoint method, using the Spiral plater in order to prepare continual antibiotic
      gradient plates, vs. the reference agar dilution MIC determination. In an attempt
      to evaluate this method, 6 different antibiotics and 10 to 20 various strains
      with each antibiotic were used: imipenem and P. cepacia, imipenem, amikacin,
      ciprofloxacin and P. aeruginosa, vancomycin, teicoplanin and Streptococcus sp.,
      Enterococcus sp., penicillin G and S. pneumoniae. The MICs obtained with the
      Spiral method were shown by regression analysis to be similar to the MICs
      obtained with the reference agar dilution method. Rates of agreement (+/- 1
      dilution) between the two methods were > or = 90 p. cent for all six antibiotics
      tested and minor discrepancies between the categories S, I, R were only found for
      imipenem and penicillin. The Spiral gradient endpoint method for MIC
      determination seems to be interesting in routine because it is a reproducible and
      sensitive method, which reduces materials and personnel time.

PMID- 7824312
TI  - [Comparison of two routine techniques for the evaluation of the susceptibility to
      antibiotics of strict anaerobic bacteria: E test AB Biodisk and ATB ANA
      Biomerieux].
AB  - A simple, rapid and reliable method that can be used to test individual isolates
      in routine is needed. Two systems are now marketed in France. As these two
      methods have not been studied extensively and never compared, the aim of our
      study was to evaluate them concurrently. For that 56 anaerobes were collected,
      including 31 Bacteroides fragilis group strains. The MIC's of 10 antibiotics were
      determined by the reference agar method. All results were further interpreted in
      SIR categories. Agreements of the results obtained for each method were assessed
      comparatively to the reference method results. For E Test and ATB ANA
      respectively, agreements of results were: 93 and 92.8 p. cent, major
      discrepancies (R/S): 4.2 and 5.7 p. cent, very major discrepancies (S/R): 3.7 and
      1.5 p. cent. Clindamycin was involved in one-third of the discrepancies observed
      with E test. This study shows that E test and ATB ANA demonstrated interesting
      alternatives for the susceptibility testing of anaerobes.

PMID- 7824313
TI  - [A simple method for the determination of the class of expression of methicillin
      resistance].
AB  - Four stable classes of phenotypic expression in methicillin resistant
      Staphylococcus aureus were described: three of them showed heterogeneous
      resistance. The fourth was homogeneous. Methicillin resistance depend on the gene
      mecA encoding an altered penicillin-binding protein. The phenotypic expression
      was controlled by chromosomic factors (fem and aux genes) and was modified by
      test conditions: (temperature - pH - NaCl 4%). The conventional method for
      determination of these different classes was the population analysis method using
      methicillin as antibiotic indicator. This fastidious method cannot use in routine
      laboratory. In this work, the authors developed a common method using the
      diffusion agar method. Four antibiotic disks (methicillin 2.5, 15, 100 micrograms
      oxacillin 30 micrograms) and three incubation temperatures (30 - 35 - 40 degrees
      C). The determination of the phenotypic classes could be an epidemiologic marker
      for the survey of epidemic MRSA in hospital.

PMID- 7824314
TI  - [Value of the E-test for the determination of the susceptibility to antibiotics
      of Neisseria meningitidis].
AB  - The E-test was evaluated by comparison with the reference agar dilution method on
      50 N. meningitidis strains belonging to serotypes A [13], B [17] and C [12] or
      not agglutinated, isolated in France and Djibouti from cerebrospinal fluid. All
      strains were sensible by the reference method to penicillin G, cefotaxime,
      chloramphenicol, ciprofloxacin, doxycyclin, rifampicin. For erythromycin, some
      strains were intermediate (7/50). N. meningitidis serogroup A ATCC 13077 was used
      as control. The E-test quantitative accuracy compared with agar dilution results
      was 80% (+/- 1 log2) or 97% (+/- 2 log2). The E-test generally showed lower
      inhibitory concentration values than the agar dilution method. Some technical
      problems appear in our experience: agar plates must be well dried; on 85 mm
      diameter agar plates only one strip can be tested. The E-test for determination
      of antibiotic resistance of N. meningitidis is an easy but expensive method,
      which give reliable results with agar dilution.

PMID- 7824315
TI  - [Determination of the susceptibility of staphylococci and enterococci to
      plycopeptides by the E-test method].
AB  - E-test was evaluated by comparison with the reference agar dilution method on 15
      enterococci and 15 staphylococci with variable resistance to glycopeptides and
      isolated from clinical samples: 15 enterococci with 3 glycopeptide-resistant (2
      E. facalis and 1 E. faecium), 1 glycopeptide intermediate E. gallinarum and 11
      glycopeptide-sensible E. faecalis; 15 staphylococci with 4 teicoplanine-resistant
      (1 S. aureus, 1 S. epidermidis and 2 S. hominis), 3 teicoplanin-intermediate (1
      S. epidermidis, 2 S. haemolyticus) and 8 teicoplanin sensible strains (6 S.
      aureus, 1 S. epidermidis and 1 S. hominis). Repeatability (10 determinations by
      strain) and exactitude were tested for all strains. Our data shows very good
      results for repeatability and exactitude with the reference method except in the
      case of coagulase negative staphylococci and teicoplanin. Some technical problems
      appear in our experience: for staphylococci, a 48 h incubation is necessary to
      detect teicoplanin-intermediate strains but 24 h is sufficient for enterococci. E
      test is expensive, require a strict methodology, but is a good method to detect
      glycopeptide resistance for staphylococci and enterococci except for coagulase
      negative staphylococci and teicoplanine.

PMID- 7824316
TI  - Antibiotic susceptibility of streptococci isolated from blood from neutropenic
      patients.
AB  - MICs were performed on 62 streptococci isolated from the blood of neutropenic
      patients from 1986 to 1992 using the NCCLS broth microdilution procedure. Species
      isolated were 43 S. mitis, 6 S.pneumoniae, 5 S.sanguis, 1 S.pyogenes, 1 beta
      hemolytic streptococcus of the group G, 1 S.adjacens, 1 S.intermedius, 4 not
      identified isolates (2 alpha-hemolytic, 1 non-hemolytic and 1 nutritionally
      variant strains). 26% of all strains were resistant or intermediate to penicillin
      (MIC 90: 2 mg/l) and 89% to norfloxacine (MIC 90: 32 mg/l). All were susceptible
      to vancomycin. Among cephalosporins, all strains were susceptible to cefotaxime
      (MIC 90: 1 mg/l), ceftriaxone (MIC 90: 1 mg/l) and cefepime (MIC 90: 2 mg/l)
      while 19% were R or I to ceftazidime (MIC 90: 16 mg/l). All were susceptible to
      imipenem (MIC 90: 0.5 mg/l) and meropenem (MIC 90: 1 mg/l). Among the third
      generation cephalosporins, ceftazidime--the agent of this class of antibiotics
      that is most often used for the empirical therapy of febrile episodes in
      neutropenic patients (in combination but also in monotherapy)--has a high
      resistance rate as compared to the other compounds.

PMID- 7824317
TI  - [Resistance of Streptococcus pneumoniae to penicillin. "Bacteriological"
      resistance/"clinical" resistance].
AB  - From January 1988 to December 1992, 143 Streptococcus pneumoniae strains have
      been isolated at a significant level from 136 patients hospitalized in the
      pulmonary care unit of CHI Creteil. The clinical presentations were: 83 pneumonia
      (P), 48 acute bronchitis (B) and 12 colonizations (C). Fourteen strains were
      found to be penicillin resistant (MIC > 0.125 mg. l-1): 11 P, 2 B, 1 C. Two
      patients were lost of view after the beginning of the treatment: a pneumonia
      (Serotype 23F, MIC = 2 mg. l-1) and a bronchitis (Serotype 23F, MIC = 2 mg. l-1).
      Treatment was pristinamycine for one and amoxicilline alone or associated to
      clavulanic acid for the other 13. We observed the failure of the treatment in
      two. A pneumonia (Serotype 23, MIC = 2 mg. l-1) was treated before
      hospitalization by josamycine (3 days), then cefpodoxime (4 days) and amoxicillin
      clavulanic acid (1.5 gr/d during 7 days). Healing was obtained with the increase
      to 3 gr/d. The other failure was a pneumonia without improvement after 11 days
      with 3 gr/d of amoxicilline. The treatment was stopped during 5 days and a
      protected brushing was performed. A Streptococcus Pneumoniae (Serotype 23F, MIC =
      8 mg. l-1) was isolated. The clinical status rapidly improved with erythromycine
      (3 gr/d) to which the strain was susceptible. "Bacteriological" Resistance to
      penicillin is demonstrated (10 percent in our sample, 17 percent in France during
      1991). However amoxicillin to a sufficient dosage is still enough ("Clinical"
      Resistance < 1 percent in our sample) for the treatment of respiratory infections
      except when the MIC is at a high level.

PMID- 7824318
TI  - [Beta-lactamase-producing Haemophilus influenzae isolated in Portugal, 1989
      1992].
AB  - Within the framework of a national multicentric study between 1989 and 1992, 118
      strains of betalactamase producing Haemophilus influenzae were isolated.
      Biotyping demonstrated the predominance of biotypes I, II and III, with 22, 36
      and 24% of the strains, respectively. Encapsulated strains accounted for 13% of
      the total; all, but one, were serotype b. The antimicrobial susceptibility test
      (dilution method) of the 118 ampicillin--resistant strains showed: 33.9%
      resistance to tetracycline, 29.7% to chloramphenicol, 10.2% to erythromycin, 9.3%
      to trimethoprim, 0.8% to rifampicin, and 29.7% of multiresistance. All strains
      were susceptible to augmentin, cefotaxime, ceftriaxone and ceprofloxacin. Ninety
      strains were screened for resistant plasmids. A large plasmid (30-50 Mdal) was
      isolated in 38.9% of the strains and a small plasmid (3-4.4 Mdal) in 10%. No
      plasmid was found in 51% of the strains. Isoelectric focusing of 54 beta
      lactamases showed that all were type TEM-1 (pI = 5.4), with the exception of one,
      which was type TEM-2 (pI = 5.6).

PMID- 7824320
TI  - [Epidemiological studies of the susceptibility of Pseudomonas aeruginosa to
      antibiotics].
AB  - The susceptibility to antibiotics of 1367 non-replicate strains of Pseudomonas
      aeruginosa isolated at Beaujon Hospital between 1990 and 1992 was investigated
      and compared with the serogroup O and the strain origin (ward, sample). Five
      betalactam resistance patterns were distinguished according to susceptibility to
      ticarcillin, piperacillin, ceftazidime and aztreonam,: 1 = SSSS, 2 = RRSS, 3 =
      RRRR, 4 = RSSR, 5 = RRSR. The other antibiotics studied were imipenem,
      tobramycin, amikacin, ciprofloxacin and fosfomycin. Resistance to all
      antibiotics, fosfomycin excepted, was higher in intensive care units than in
      other wards. The respective frequencies of the phenotypes were: 70.3%, 4.3%,
      11.8%, 10.2% and 3.4%. The frequency of pattern 3 steadily increased between 1990
      and 1992 at the expense of pattern 1, whereas patterns 2, 4 and 5 remained
      stable. The most common serogroups were O6 (15.8%), O11 (14.5%) and O1 (9.9%).
      The O11 strains were more widespread in intensive care units than in other wards
      and were more resistant to antibiotics. Most of the O12 strains displayed pattern
      2 and were highly resistant to antibiotics.

PMID- 7824319
TI  - [Properties of a cephalosporinase produced by Proteus penneri inhibited by
      clavulanic acid].
AB  - P. penneri produces an inducible cephalosporinase, as many Enterobacteriaceae.
      Nevertheless this betalactamase is susceptible to clavulanic acid which is an
      exception also encountered for P. vulgaris. The authors studied the enzyme
      produced by P. penneri 14HBC resistant to cefotaxime (MIC 16 mg/l) isolated in
      Spain in 1992. This betalactamase of isoelectric point 6.65 hydrolyzes first
      generation cephalosporins, amoxycillin and poorly ticarcillin as it occurs for
      all cephalosporinases. However, this enzyme hydrolyzes strongly oxyimino
      cephalosporins: cefuroxime, cefotaxime, cefepime, cefpirome as it occurs with
      extended-spectrum betalactamases. Cephamycins and imipenem are not substrates.
      Clavulanic acid has a very good affinity for this betalactamase which is
      inactivated progressively. These properties are similar to those of the enzyme of
      P. vulgaris Ro104 of isoelectric point 8.3 which, contrarily to other
      cephalosporinases, belongs to the structural Ambler's class A.

PMID- 7824322
TI  - [Production of elastase, exotoxin A and alkaline protease during bronchopulmonary
      exacerbations in patients with mucoviscidosis chronically infected by Pseudomonas
      aeruginosa].
AB  - The authors have studied the production of exoproteins by Pseudomonas aeruginosa
      in the sputa of 18 patients suffering from cystic fibrosis, during 29
      bronchopulmonary exacerbations and also after the recovery of a stable state.
      Significant levels of exoproteins were detected but with a large heterogenity of
      intra and inter individual variations. A significant decrease in the production
      of the three exoproteins was found after twelve days of antibiotherapy, without
      any correlation between exoprotein levels and colony forming units in the sputa.
      During the intercrisis phase, exoproteins levels were practically undetectable.
      These facts and the good correlation between clinical symptoms support the
      hypothesis of a renewal of virulence of Pseudomonas aeruginosa during these
      periods of bronchopulmonary exacerbation in cystic fibrosis.

PMID- 7824321
TI  - [Susceptibility of strict anaerobic bacteria to antibiotics in France: a
      multicenter study].
AB  - During 1992, the in vitro antibiotic susceptibility of 462 anaerobic bacteria was
      performed in 7 hospitals, by the reference agar dilution method. Among the 222
      Bacteroides fragilis group strains, only one Bacteroides fragilis strain was
      resistant to imipenem and all betalactams, even combined with betalactamase
      inhibitors while metronidazole resistance could not be detected. One major outer
      membrane protein (probably a porin) was lacking in some of the six amoxicillin
      clavulanic acid resistant Bacteroides fragilis group strains. Evolution in
      antibiotic resistance rates could be assessed only for clindamycin and
      piperacillin whose resistance rates increased to 14 and 15.8 p. cent,
      respectively. On the whole anaerobic strains resistance rates were: imipenem 0.2,
      ticarcillin-clavulanic acid 0.5, amoxicillin-clavulanic acid or metronidazole
      1.5, piperacillin 9.1, cefotaxime-sulbactam 9.7, cefoxitin 12.8, clindamycin
      13.7, cefotaxime 27.2, amoxicillin 45 and ciprofloxacin 70, respectively.

PMID- 7824323
TI  - [Virulence of Listeria monocytogenes in pregnant mice].
AB  - Serious food-borne outbreaks of listeriosis have been reported in North America
      and in Europe, during the past decade. The predominant risk groups appear to be
      immunocompromised adults, elderly people, newborn babies and pregnant women. In
      order to examine the relationship between alimentation, listeriosis and pregnant
      females, we developed an experimental model using Swiss mice fed ad libitum
      during 4 days with pellets containing a high concentration of Listeria
      monocytogenes serovar 4b (10(9) u.f.c/g). Samples were taken from many series of
      pregnant mice which had been infected respectively by L. monocytogenes from 6th,
      10th, 14th and 18th day of pregnancy onwards. This was compared to non infected
      control series. The transmission of infection from mother to progeny and
      contamination of surviving progeny were evaluated by Listeria numeration in
      liver, brain and intestines. Females infected between day 6 and day 10, and
      between day 10 and day 14 after fertilization, aborted or died of encephalitis.
      Mice contaminated between day 14 and day 18, were the least prone to experimental
      listeriosis. On the other hand, some mice contaminated between day 18 and day 22,
      i.e. at the end of their pregnancy, may develop encephalitis a few days after
      parturition of a healthy litter. Series contaminated between day 6 and day 10,
      and between day 10 and day 14 turned out to be highly sensitive to the
      transmission of infection from mother to young. In two other series (day 14--day
      18; day 18--day 22), the young mice contained generally no Listeria. Our
      experimental model shows the relationship between listeriosis and alimentation.
      In pregnant mice, sensitivity to infection depends on their gestational status
      with large individual variability.

PMID- 7824324
TI  - [Concentration of amoxicillin in neonates after infusion to the mother during
      labor].
AB  - Amoxicillin is effective against S. agalactiae (MIC 50 = 0.03 mg/l). Neonatal
      prophylaxis of GBS infection had already been studied but very few data are
      available regarding pharmacokinetic of these antibiotics. In this study, 58
      pregnant women with GBS colonisation and/or with epidemiologic risk factors
      received intrapartum antibiotic infusion at the beginning of the labor (1 g
      amoxicillin every 6 hours until the delivery). At delivery, cord blood and
      gastric fluid were taken in delay from 0.5 to 6 hours after the beginning of the
      infusion. Dosages were done in triplicate with a microbiological method using
      Bacillus subtilis ATCC 6633 as test strain. In cord blood amoxicillin appeared as
      early as the first half hour. Concentration were from 5 to 7 mg/l between 1 hour
      and 4 hours after the beginning of the infusion, and from 3 to 4 mg/l after 4
      hours. In gastric fluid, concentrations obtained were over 1 mg/l after 1.5 hour
      and over 3 mg/l after 2.5 hours with good efficiency even after the sixth hour.
      The protocol using a slow intrapartum amoxicillin infusion (1 g) gave
      concentrations in gastric fluid and cord blood over S. agalactiae MIC.

PMID- 7824325
TI  - [Penetration of vancomycin in cardiac and mediastinal tissues in humans].
AB  - Vancomycin penetration into heart tissues (valves, myocardium, auricles and
      pericardium) and mediastinal tissues (fat and sternal bone) after two regimens of
      administration was evaluated in a prospective, randomized study. Twenty adult
      patients undergoing mitral or aortic valve replacement were included in the study
      and divided into two groups of ten patients each: Group 1 patients were
      administered a 15 mg/kg intravenous dose of vancomycin over 90 min upon
      anesthesia. Group 2 patients received the same dose followed by a second 7.5
      mg/kg intravenous dose of vancomycin over 30 min at time of initiation of the
      cardiopulmonary bypass. In both groups further vancomycin administrations (10
      mg/kg) were performed on hour 8, 16 and 24. Plasma and tissue vancomycin
      concentrations were assayed by fluorescence polarization immunoassay. At
      different times of the surgical procedures (thorax opening and closure, period of
      cardiopulmonary bypass) 67 to 100% of the patients in group 1 had vancomycin
      concentrations in the studied tissues above the MIC 90 for Staphylococcus aureus
      (1 microgram/g) and Staphylococcus epidermidis (2 micrograms/g). In group 2, for
      the same periods and the same tissues, 72 to 100% of patients had adequate
      vancomycin concentrations. In group 1 patients, mean ratios of vancomycin tissue
      concentrations/MIC 90 were 6 +/- 2 to 20 +/- 4 for Staphylococcus aureus (MIC 90:
      1 microgram/g) and 3 +/- 1 to 10 +/- 4 for Staphylococcus epidermidis (MIC 90: 2
      micrograms/g). In group 2 patients, mean ratios were 8 +/- 3 to 20 +/- 4 for
      Staphylococcus aureus and 4 +/- 1 to 10 +/- 3 for Staphylococcus epidermidis. The
      use of a second dose of vancomycin in group 2 significantly increased plasma
      concentrations (P > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7824327
TI  - Prevalence of HIV infections among patients attending a Parisian anonymous
      testing center between 1988 and 1993.
AB  - The prevalence of HIV infection was assessed among 15,611 consecutive patients
      attending a Parisian anonymous testing center from April 1988 to June 1993. Sera
      (17,910) were tested for the presence of anti-HIV antibodies using two different
      enzyme-linked immunosorbent assays. Seropositivity was verified by Western
      blotting. The sera were also assayed for HIV antigenemia detection in 2,493
      cases. Six hundred and seventy-seven patients were found to be anti-HIV antibody
      positive: among them 666 were infected by HIV-1 and only 11 by HIV-2. Antigenemia
      was detected in 108 samples (4.3%). In all cases but 5, antigenemia was
      associated with the presence of specific antibodies. Risk factors for HIV
      infection could be determined for 5,735 patients. The HIV prevalence rates were
      5.2% in 1988-89, 4.9% in 1990, 3.4% in 1991, 2.8% in 1992 and 1.8% for the 6
      first months of 1993 (p < 0.01). Only one patient was coinfected with HTLV-1.
      This study shows a trend of decreasing seropositivity rates among the patients
      attending the anonymous testing center since 1990. By contrast, the percentage of
      seropositive patients with antigenemia was stable between 1988 and 1993.

PMID- 7824326
TI  - [Continuous infusion of vancomycin during the neonatal period].
AB  - Twenty-five infants with suspected or confirmed coagulase negative staphylococcal
      infection were studied. Continuous administration of vancomycin was used because
      it is usual with infusions prepared daily for catheterized patients, and because
      continuous infusions are well tolerated and achieve better penetration in tissues
      and CSF. Vancomycin acts as a time-dependent antibiotic. The aim was to obtain a
      level of 20-25 mg/l. in serum. Fifteen newborns term 27-35 weeks (m = 30.3) aged
      7-30 days (m = 16.1) received 10 to 45 mg/kg/day of vancomycin and were monitored
      for 2 to 12 days. The sample for assay was taken in a peripheral vein, and the
      results were the same during the infusion or 15 minutes after its end. The daily
      dose of vancomycin necessary varied from 25 to 40 mg/kg for newborns with serum
      creatinine < 70 mmol/l and 10 to 30 mg/kg with serum creatinine > or = 90 mmol/l.
      Except for a newborn with multiorgan failure, serum creatinine rapidly decreased.
      Four newborns term 38-40 weeks (m = 39.5) aged 2-12 days (m = 8.3) received 20 to
      45 mg/kg/day of vancomycin and were monitored for 2 to 12 days. The daily dose
      necessary varied from 30 to 40 mg/kg/day with important individual variations,
      and 20 mg/kg/day in a newborn with a high level of creatinine. In 6 infants aged
      2-22 months receiving 22-45 mg/kg/day of vancomycin, a mean daily dosage of 40-45
      mg/kg was adequate, with important individual variations.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7824328
TI  - [Prevalence of HBs Ag in about 21,500 pregnant women. Survey at twelve French
      University Hospitals. The Muticentric Study Group].
AB  - The risk of perinatal B virus transmission is estimated in France on results of
      limited studies carried out during a long period and essentially in metropolitan
      area. Systematic screening for HBsAg in pregnancy was decided in February 1992 in
      France. In order to obtain national data on HBsAg prevalence of pregnant women,
      the authors have summarized the results obtained from twelve French university
      hospitals during one year. Among the 21,476 pregnant women studied (French:
      16,351 and immigrant: 5,125), the total HBsAg prevalence was 0.72% and was
      significantly higher in the immigrant women group (2.56%) when compared to that
      of French women (0.15%). The HBsAg prevalence increased from Mediterranean area
      (1.75%) to SubSaharan Africa (4.61%) and South East Asia (5.45%). Important
      variations were observed between the centers (from 0.13 to 2.99%). Among the
      HBsAg carriers, 16.5% were HBeAg and/or HBV-DNA positive in their serum. The only
      means to prevent each year in France around 850 chronic HBV infections by
      vaccination of the neonates consist in systematic HBsAg screening.

PMID- 7824329
TI  - [Value of the score for Gram strains in the diagnosis of bacterial vaginosis].
AB  - The interpretation of Gram-stained slides of vaginal swab specimens is evaluated
      for the diagnosis of bacterial vaginosis and correlated with the isolation
      bacteria and clinical signs: thin homogeneous vaginal discharge, pH > or = 4.7,
      amine odor and presence of clue cells. Gram stained smears were scored following
      a morphotype classification: (a)-Lactobacillus morphotypes (scored 4 to 0), (b)
      small Gram negative (G. vaginalis, scored 0 to 4), (c)-curved Gram variable rods
      (Mobiluncus morphotypes, scored 0 to 2). The scoring system (0 to 10) was a
      weighted combination of these morphotypes: a+b+c. The criterion for bacterial
      vaginosis was a score > or = 7, a score of 0 to 6 was considered as no bacterial
      vaginosis. Samples of 709 women, aged 18 to 84 (mean age = 39.7) were examined.
      The prevalence of G. vaginalis culture was 12.5%, and Mobiluncus infection
      occurred in 1.5%. The frequency of M. hominis was diagnosed in 2.8% of women. A
      score of 7 to 10 on Gram stain was observed in 9.7% in the population. Compared
      to G. vaginalis culture, Gram stained smear was more sensitive (0.71) than
      clinical signs of bacterial vaginosis (0.46). The specificity was similar with
      the two methods. The assessment of G. vaginalis morphotypes was highly correlated
      with the G. vaginalis culture (p < 0.001, OR = 248). The infection of T.
      vaginalis or Candida sp. was never associated with a score > or = 7. The Gram
      stained smear is a cheap, fast and easy method. It provides good results for
      diagnosis of bacterial vaginosis.

PMID- 7824331
TI  - Pulsed field gel electrophoresis for molecular epidemiology of penicillin
      resistant Streptococcus pneumoniae strains.
AB  - The emergence of strains of Streptococcus pneumoniae resistant to penicillin and
      other antibiotics has become a major concern for antimicrobial therapy of
      pneumococcal infections. The spread of that resistance over the world increases
      the need for their epidemiological surveillance: specific epidemiological markers
      are required. In this study, pulsed field gel electrophoresis of genomic DNA was
      carried out on sixteen resistant isolates of S. pneumoniae from different parts
      of the world and fifteen resistant isolates from Toulouse. The restriction
      endonucleases ApaI and SmaI were used to digest intact chromosomes and the
      fragments were resolved by field inversion gel electrophoresis (FIGE). Each
      digest produced 10 to 19 fragments for comparison between strains. The
      polymorphism obtained with FIGE was greater than that obtained with serotyping
      which appeared to be not a good criterion for genetic relatedness. Three common
      clones could be recognized among the penicillin-resistant isolates. Two clones
      were found in Spain and in Toulouse and were associated with serotypes 6B and 9V,
      respectively. The third clone was isolated in South Africa and in Spain and
      contained serotype 23F isolates and one serotype 19F strain. The FIGE profiles
      observed in this study also demonstrated that serogroup 23 multiresistant strains
      isolated in Toulouse are genetically closely related and might have originated
      from the same Spanish 23F clone. These results underline the importance of the
      geographic spread of resistant clones in the increase in the incidence of
      penicillin-resistant pneumococci. They indicate that pulsed field gel
      electrophoresis should be an effective tool for the typing of resistant S.
      pneumoniae strains capable of tracing their origin.

PMID- 7824330
TI  - [Serotyping of group B streptococcus in microbiological samples at the Robert
      Ballanger hospital].
AB  - From February to September 1993, we have established the serotype of group B
      Streptococcus (GBS) taken from diverse microbiological samples, in particular
      from gastric liquids. The method utilized was a technic of coagglutination (Dako
      Group B Streptococcus Serotyping Test, France) allowing the search for serotypes
      Ia, Ib, II, III, IV and V. All in all, 169 samples have been tested: 117 vaginal
      samples, 17 diverse samples, 26 gastric samples, 3 placentas and 7 ammmiotic
      liquids. Serotypes are spread as follow: III (41), II (33), Ia (26) et V (23)....
      Usually, serotype III was the most frequently found and the most virulent,
      particularly in infections in neonates.

PMID- 7824332
TI  - [Effect of the tranquilizer gidazepam on the behavioral reactions of rats in the
      first weeks after resuscitation].
AB  - The experiments have indicated that the first week of postresuscitation is marked
      by enhanced goal-investigating behaviour in the open field, by the accelerated
      learning of an operant reflex, and by decreased anxiety in the conflict situation
      test in male rats undergone a 10-min arrest of systemic circulation. There was a
      depressive behavior in the open field following 6-8 weeks with the normalization
      of operant reflex learning and the level of anxiety in the conflict test
      situation. Gidazepam (3 mg/kg, i.p.) produced a sedative effect in the first week
      after resuscitation, then 6-8 weeks later it displayed its anxiolytic and
      activating effect which is similar to this dose of the agent given to intact
      animals. The findings suggest that there are changes in the pattern of
      neurophysiological abnormalities, as well as a response of the benzodiazepine
      receptor complex to drugs during a resuscitative process, which may be one of the
      components of formation of a post-resuscitative central nervous abnormality.

PMID- 7824333
TI  - [Behavioral signs of neuropathic pain in cats due to compression of the
      infraorbital nerve].
AB  - The changes in behavioral reactions were studied in cats after incomplete
      compression of the infraorbital nerve by means of two ligatures as a model of
      trigeminal neuropathy. It was found that there appeared a behaviour protective
      the damaged side of the face, sudden standstills of the animals which threw their
      head back and raised their anterior paws to the face, as well as inhibition of
      motor activity. Decreases in the nociceptive threshold and the threshold of
      emotionally affective responses to lip electrostimulation as the sensory
      threshold increased. These behavioral changes are regarded as signs of
      spontaneous pain and hyperalgesia in animals with nerve compression, and the used
      model is considered to be adequate for studying the mechanisms of neuropathic
      pain.

PMID- 7824334
TI  - [Prediction of potential motor disorders in babies from neonatal serum biological
      test findings].
AB  - To predict motor activity in the newborn, electromyographic (on rats) and
      ultrastructural (on chick embryos) studies were performed after administration of
      donor babies' sera taken in the first days of life. Morphological and
      electromyographic parameters were compared with late clinical symptoms. A rating
      schedule was developed with regards to biological test results, which allows
      motor disorders to be detected in the newborn.

PMID- 7824335
TI  - [Responses of the blood system during the stages of resistance and exhaustion in
      chronic emotional stress after gamma-irradiation at a dose of 90 rad].
AB  - The rat experiments have demonstrated that prior gamma-irradiation in a dose of
      0.9 Gy have an inhibitory effect on the development of hyperplasia of the bone
      marrow during common adaptation syndrome resistance in emotional stress. The
      animals, irradiated during exhaustion, earlier developed hypoplasia of
      hemopoietic tissues.

PMID- 7824336
TI  - [Analysis of cellular and humoral mechanisms of the anti-radiation action of the
      drug HC-1539].
AB  - The agent HC-1539, an analogue of tamoxifen, was studied for its effects on the
      blood system of intact animals and on the time course of postradiation recovery
      of hemopoiesis. HC-1539 given to the mice unexposed to radiation reduced bone
      marrow levels of CFUs (a colony of forming units in the spleen) and CFU-GM (that
      in the granulocyte-macrophages) and increased splenic counts of granulocyte
      macrophage precursors. There was also a decrease in the proliferative activity of
      CFU-GM 1 and 5 days after the drug administration and an increase in serum GM-CCP
      levels when the agent showed the peak of its radioprotective effect. In the HC
      1539-treated mice, there was a more intensive normalization of the CFUs of CFU-GM
      myeloid and erythroid hemopoietic populations than in the radiation-exposed ones.
      Thus, the mechanisms responsible for the radioprotective action of HC-1539 may be
      associated both with its direct effects on the proliferation and differentiation
      of hemopoietic cellular precursors and with the stimulation of release of growth
      differential factors by hemopoietic microenvironmental elements.

PMID- 7824337
TI  - [Dynamics of the interrelationships of functional and morphologic parameters of
      the left and right ventricle in coarctation and decoarctation of the ascending
      aorta].
AB  - The contractile and ultrastructural parameters of the left and right ventricles
      were studied in rabbits 3 weeks after ascending aortic coarctation by a third of
      the baseline diameter. In other rabbits, the same parameters were studied 1, 2,
      3, and 4 weeks after recovery of the normal aortic lumen following three weeks of
      its narrowing. It was found that a rapid recovery of the parameters under study
      did not occur after decoarctation despite the fact that left ventricular overload
      was abolished. A fortnight after decoarctation there was a profound increase in
      the contractility of the two ventricles and three weeks there was a significant
      enhancement of cardiomyocytic mitochondrial function.

PMID- 7824338
TI  - [Changes in the chrono-inotropic properties of the myocardium and oxygen
      consumption as affected by strophanthin-K, isoptin and their combination].
AB  - In the experiments on isolated frog atria isometrically contracting, the author
      studied myocardial contractility and oxygen consumption under the action of
      strophanthin K, isoptin, and their combination. Strophanthin was demonstrated to
      exert two-phase effects on the inotropic function of an isolated myocardial
      stripe, which depended on the time of cardiotonic action. The calcium antagonist
      isoptin in combination with strophanthin K reduced myocardial oxygen uptake,
      potentiated the negative chronotropic effect of the cardiac glycoside, decreased
      the cardiostimulant action of the latter, slowing down its development.

PMID- 7824339
TI  - [Specific nature of the development of myocardial blood vessels as one of the
      conditions of compensatory cardiac reserves].
AB  - The mechanism responsible for the formation of cardiac connective tissue and
      vascular components in early ontogenesis from various embryonal layings and the
      subsequent coexistance and interaction of two myocardial blood supply system in
      the formed heart at all stages of postnatal life form the basis for morphological
      and functional characteristics of organ specificity. The findings are of direct
      interest to practical cardiologists and cardiosurgeons who analyze some
      conditions which are likely to involve compensatory mechanisms in inadequate
      coronary blood supply of the heart.

PMID- 7824340
TI  - [Various delayed forms of postresuscitation pathology of the autonomic nervous
      system].
AB  - In rats which had sustained clinical death and resuscitation, which were
      compatible with apparent complete recovery of the neurological status,
      responsiveness of the autonomic nervous system was studied from the changes
      occurred in blood pressure, heart and respiration rates within 2 hours of
      restrictive exercise at some stages of the late postresuscitation period--1.5-2,
      3.5, and 4.5 months after reanimation. The responsiveness of the autonomic
      nervous system was compared with changes in conditioned reflex performance (a
      situational food instrumental conditioned reflex (SFICR)). There were progressive
      stage-specific changes in the responsiveness of the autonomic nervous system as
      an increasing trend towards to persistent hypertension during restrictive
      exercise. The functional failure of the autonomic nervous system during a
      postresuscitation process coincided with autonomic nervous abnormalities which
      were detected in responses to acute or long-term stresses, showing more profound
      SFICR changes than in intact animals.

PMID- 7824341
TI  - [Effect of sodium nucleinate on ventricular arrhythmia and blood level of medium
      molecular weight peptides in an experiment].
AB  - The experiments on 18 isolated albino rat hearts have shown that sodium
      nucleinate exerts a protective action on the occurrence of reperfusion
      ventricular arrhythmias. Sodium nucleinate was given orally in a daily dose of
      50/kg for 2 weeks. The agent reduced the blood concentrations of medium-weight
      molecular peptides, which may be regarded as the liquidation of a factor
      predisposing to arrhythmias. Other possible mechanisms responsible for the
      antiarrhythmic activity of sodium nucleinate, which are adaptable to the
      immunomodulating and membranoprotective properties of the drug, as well as to its
      ability to enhance intracellular metabolism are also discussed in the paper.

PMID- 7824342
TI  - [Protective effect of a beta-1,3-carboxymethylglucan in acute massive blood
      loss].
AB  - Experiments were performed on CBA mice to study the effect of intravenous
      injections of beta-1,3-f-carboxymethylglucan (Bratislava, Slovakia) during acute
      massive blood loss (50% of the total blood volume). Two different fractions were
      used in doses of 25 mg/kg of body weight. The first fraction (semisoluble, its
      molecular weight being about 10(6)) was shown to have a potent protective effect
      when it was injected 24 h before blood loss. On the contrary, the other fraction
      (water soluble, its molecular weight being less than 1.2 x 10(6)) showed no
      protective effect. Moreover, injection of this fraction 72 h before blood loss
      can lead to increases in deaths among the mice.

PMID- 7824343
TI  - [Comparative effectiveness of the peptide drugs finoptin, levamisole and
      prednisolone in immune cardiogenic shock in an experiment].
AB  - The efficacy of dalargin, delta-sleep peptide, finoptin, levamisole, and
      prednisolone was studied in 104 white mice with experimental immune cardiogenic
      shock. The efficacy of finoptin was as high as that of prednisolone. Dalargin,
      delta-sleep peptide, levamisole, and T-activon decreased mice's life span and/or
      increased their mortality when the mice were given intravenous infusions of these
      agents.

PMID- 7824344
TI  - [Changes in the activity of lipid peroxidation in the myocardium of adult and
      aged rats under stress].
AB  - The levels of lipid peroxidation (LPO) products, the antioxidative system and
      morphometric changes were studied in the myocardium of adult (8-10-month) and old
      (20-24-month) male rats in different periods after their exposure to stress. The
      findings suggest that the maximum damaging action occurs 18-60 hours of
      poststress. The high activity of LPO and the low activity of the antioxidative
      system in the hearts of the old animals determine more substantial impact of
      stress on the myocardium of this group of animals.

PMID- 7824345
TI  - [Lipid peroxidation in experimental arterial hypertension].
AB  - The studies were conducted on mature non-inbred male rats. Renovascular
      hypertension (RAH) was induced by aortic ligation between the renal arteries. The
      rats were included into the experiment following 14 days (acute PAH) and 1.5
      months (chronic RAH) of ligation. The hypertensive rats displayed activated lipid
      peroxidation (LPO) processes, especially in rats with severe chronic PAH that had
      elevated serum levels of dienic conjugates and malonic dialdehyde as compared
      with control rats. Concurrently, the status of some antioxidative systems of the
      body was assessed--the concentration of tocopherol-like compounds and total
      sulfhydryl groups were measured. There were no changes in the levels of
      tocopherols in RAH rats as compared with the control, regardless of the duration
      of RAH. The content of total sulfhydryl groups declined in rats with acute RAH,
      in those with chronic RAH in particular, which is likely to be due to the
      depletion of reducing equivalents involved in the protection of cellular
      membranes from LPO metabolites excessively formed in RAH.

PMID- 7824347
TI  - [Mechanisms of renal adaptation to disorders of water-electrolyte balance in
      metabolic acidosis].
AB  - The albino rat experiments have demonstrated that despite the type, metabolic
      acidosis causes an increase in plasma and urinary osmolarity, hyperkalemia and
      hypernatremia, enhanced urinary excretion of potassium, phosphates, and titrated
      acids with a tendency for the glomerular filtration rate and urinary pH to be
      lowered with the increased concentrations of plasma vasopressin and insulin and
      renal cortical PGE2. Hyperchlorinemic acidosis without increases in the anion
      difference is accompanied by severe chloremia, natriuresis, chloruresis,
      ammoniuresis without diuretic changes with the inhibited renin-aldosterone system
      and progesterone synthesis. Lactate acidosis with a growing anion difference
      leads to lower diuresis, Na+ and Cl- excretion without enhancing ammonium
      excretion in the presence of elevated plasma levels of renin, aldosterone, and
      progesterone. It is concluded that in metabolic acidosis, adaptation to water
      electrolytic exchange derangements greatly depends upon the type of metabolic
      acidosis and it is mediated by hormones to a considerable extent.

PMID- 7824346
TI  - [Features of reoxygenation-induced damage to ischemic kidney during heparin
      administration].
AB  - Albino rat experiments were undertaken to examine the protective action of
      heparin and the specific features of secondary renal ischemic changes when the
      agent was administered in different doses during revascularization. Ischemia was
      induced by 90-min ligation of the renal vessels and the ureter. Heparin was found
      to have a dose-dependent capacity to prolong rats' survival after ischemia of a
      single kidney. There were qualitative distinctions of morphological changes in
      the heparin-treated kidneys as compared with those in the control.

PMID- 7824348
TI  - [Electrical properties of limb muscular tissue in acute circulatory hypoxia].
AB  - The study was undertaken to examine dispersion of the complex electric resistance
      and capacitive impedance of limb muscular tissue in the frequency range of 1 to
      100 kHz in acute circulatory hypoxia caused by blood exfusion from the common
      carotid artery at 10-50% of the circulatory blood volume (CBV) at the same time
      local blood flow and oxygen tension in muscles were measured. Blood loss of 10
      30% of CBV resulted in increased muscular tissue electric conductivity.
      Decompensated blood loss was characterized by a steady growth of complex electric
      resistance and capacitive impedance. There were the greatest changes in electric
      conductivity in the frequency range of 1-10 kHz.

PMID- 7824349
TI  - [Nature of the changes in ischemic muscle impedance in excitation by pulsed
      current].
AB  - The article discusses the results of studying the impedance of a contracting
      skeletal muscle in normal blood supply and in various forms of ischemia. From
      analysis of the authors' own findings and the literature data it is concluded
      that intravascular movement of blood is the main contributor to changes of
      electroconductivity of a skeletal muscle during its contraction.

PMID- 7824350
TI  - [Use of liquid sorbents based on chitosan for treatment of diffuse forms of
      peritonitis].
AB  - Chitosan-based gelatinous affinity sorbent containing 9 mg/ml of polymyxin B was
      injected into the infected peritoneal cavity for twenty-four hours for
      detoxification in diffuse peritonitis. The clinical assay of blood plasma
      (Spectrum Abbot, USA) revealed that the lavage of the infected abdomen by
      polymyxin B-containing adsorbent resulted in systemic detoxification. The effect
      was associated with normalization of direct bilirubin, cholesterol, and
      triglyceride levels, a 4-fold decrease in uric acid levels, and a 34-fold
      increase in alkaline phosphatase activity, and a greater than 70-fold enhancement
      of hepatic aspartate aminotransferase activity.

PMID- 7824351
TI  - [Mechanism of disorders of the cerebral blood supply during stress in
      spontaneously hypertensive rats].
AB  - The immobilization- and sound stimulus-induced changes in cerebral circulation
      were studied in spontaneously hypertensive rats. It was found that there was a
      stress-induced increase in the levels of epinephrine and norepinephrine in brain
      tissue, which was associated with lower levels of vasoactive prostaglandins E and
      F2 and with their imbalance with vasodilator prostaglandins E being prevalent.
      The change in the cerebral ratio of biologically active substances results in
      cerebral blood flow autoregulation failure and development of large cerebral
      hemorrhages.

PMID- 7824352
TI  - [Models of acute transitory cerebral ischemia in cats].

PMID- 7824353
TI  - [Use of myocardial morphologic characteristics to reveal individual features of
      the body's response during administration of isadrin].

PMID- 7824354
TI  - [A photocolorimetric method for evaluating the dynamics of blood filling in the
      frog web].

PMID- 7824355
TI  - [Problem of training of specialists in the field of laboratory diagnosis].

PMID- 7824356
TI  - [The new practical study "Thrombosis and thrombolysis"].

PMID- 7824357
TI  - [Role of the sympathetic adrenal system in the pathogenesis of traumatic
      disease].

PMID- 7824358
TI  - [Hemodynamic and cerebrospinal fluid dynamic changes in acute brain prolapse].
AB  - Experiments on 19 mongrel dogs were made to examine hemo- and liquorodynamic
      changes in acute brain prolapse. It was found that irritation of the hypothalamic
      region resulted in elevated intracranial, sagittal sinus, systemic arterial and
      venous pressures. The rate of cerebrospinal fluid production in acute brain
      prolapse increased four-fold as compared with the baseline values. It is
      concluded that in acute brain prolapse, increased cerebrospinal production rate
      and enhanced brain blood filling led to intracranial decompensation.

PMID- 7824359
TI  - Dysspondyloenchondromatosis in the newborn. Report of four cases.
AB  - Dysspondyloenchondromatosis is a rare form of generalised enchondromatosis with
      hypoplastic/dysplastic changes in the lower thoracic and upper lumbar spine. The
      disease presents at birth as neonatal dwarfism and is characterised later in life
      by marked shortening of stature, unequal length of the extremities and early
      development of kyphoscoliosis. We report four newborn babies--three boys and a
      girl--with dysspondyloenchondromatosis, who had skeletal survey performed shortly
      after birth. The condition can be established in the newborn, as the radiographic
      examination (skeletal survey) shows diagnostic radiographic findings.

PMID- 7824360
TI  - Gorham's disease or vanishing bone disease: plain film, CT, and MRI findings of
      two cases.
AB  - Gorham's disease may develop in any region of the skeleton, but shows a
      predilection for the bones of the shoulders and pelvic girdles. Less frequently,
      the disease may involve the spine, and it is the proximity to the spinal cord
      which may worsen the patient's outcome. We report the clinical outcomes of two
      children with typical, yet differently localized involvement, and also review the
      plain film, CT and MRI findings.

PMID- 7824361
TI  - The boneless neonate: a severe form of achondrogenesis type I.
AB  - We report a case of a severe form of achondrogenesis type I. Prenatal
      ultrasonography showed a micromelic fetus; bony structures could not be
      identified. Postnatal radiographs revealed some foci of ossification in the ossa
      ilia, the clavicles, the upper and the lower jaw and the base of the skull. The
      long bones, the vertebral column and the ribs were not visible. The diagnosis was
      established by histologic examination of the growth plates.

PMID- 7824362
TI  - Sponastrime dysplasia: report on a male patient.
AB  - We report on a boy in the fourth family known to be affected with sponastrime
      dysplasia. The clinical and radiological features are presented. In this patient,
      the ossification delay was severe. The pattern of inheritance of this condition
      is discussed.

PMID- 7824363
TI  - MRI findings in Caffey's disease.
AB  - A patient with infantile cortical hyperostosis (ICH) is presented. Common
      features in all reported patients include: onset in the early part of the 1st
      year, tender swellings in more than one site and multiple scattered hyperostoses
      shown by radiography, but no previous study has determined the cause or origin of
      ICH. Biopsy of bony lesions only reveals hyperplasia of the lamellar cortical
      bone, without inflammation or subperiosteal haemorrhage. Although MRI resulted in
      excellent images for differentiation between bony and soft tissue structures and
      for evaluation of the extent of soft tissue involvement, it had no additional
      value in the management of the patient. Only in questionable cases can MRI
      provide additional information about the presence of a subperiosteal haemorrhage.
      Radiographic examination, in addition to clinical history and physical
      examination, is considered sufficient with regard to differential diagnosis and
      follow up of ICH.

PMID- 7824364
TI  - Soft tissue signal abnormality associated with eosinophilic granuloma.
      Correlation of MR imaging with pathologic findings.
AB  - Six patients with eosinophilic granuloma were studied retrospectively in order to
      correlate the MRI appearances with the pathology. Ages ranged from 2 years 6
      months to 11 years. The bones involved were the humerus, ulna, radius, femur,
      clavicle and ilium. Plain films, MRI and pathology specimens were obtained. A
      lytic lesion with indistinct margins, endosteal erosions and periosteal reaction
      was seen in all cases on plain radiographs. Bone marrow signal was decreased on
      T1-weighted images and increased on T2-weighted images throughout the bony lesion
      in all cases. T2-weighted images showed extensive soft-tissue abnormalities
      suggesting inflammatory changes in four cases. In two cases abnormalities were
      limited. Extensive changes correlated histologically with an early phase lesion.
      Localized minor changes were associated with a mid-phase lesion. Inflammatory
      soft-tissue changes could be associated with eosinophilic granuloma. The size of
      the soft tissue mass correlated well with the activity of the bony lesion.

PMID- 7824365
TI  - Osteomyelitis and pyogenic infection of the sacroiliac joint. MRI findings and
      review.
AB  - Acute pyogenic sacroiliac joint infection and osteomyelitis of adjacent bones
      often present with severe, poorly localized lower back, pelvic or hip pain. Five
      cases of sacroiliac joint infection or sacroiliac bone osteomyelitis were
      evaluated by MRI. MRI may be a helpful diagnostic tool to evaluate early changes
      of infection in the sacroiliac area. It is very sensitive for detecting bone
      marrow abnormalities; however, it is non-specific and can not accurately
      differentiate osteomyelitis from sacroiliitis.

PMID- 7824366
TI  - Early detection of subperiosteal abscesses by ultrasonography. A means for
      further successful treatment in pediatric osteomyelitis.
AB  - Subperiosteal abscess (SA) is a well-known complication of osteomyelitis (OM) in
      children. The efficiency of treatment of OM with this complication is dependent
      on early drainage of the abscess. We present a prospective study of 32 children
      with clinical suspicion of OM. Ultrasonography detected SA in 13 of these
      children. In nine cases OM with SA was confirmed surgically and in the remaining
      four other radiographic modalities and/or blood cultures supported the
      sonographic diagnosis. In the remaining 19 cases, OM without SA was the final
      diagnosis.

PMID- 7824367
TI  - High resolution sonography using modern equipment.

PMID- 7824368
TI  - Mesomelic dysplasia.

PMID- 7824369
TI  - Gas gangrene limited to the right lobe of the liver after orthotopic liver
      transplant: sonographic, plain film and CT findings.

PMID- 7824370
TI  - Disseminated hepatic and splenic calcifications following cat-scratch disease.
AB  - Patients with cat-scratch disease (CSD) may develop visceral manifestations such
      as hepatic and splenic granulomas. Normally, the granulomas disappear within 1-5
      months. Two previous reports have described the evolution of splenic lesions into
      small calcifications. We report a case of cat-scratch disease in which long
      lasting multiple and disseminated hepatic and splenic granulomas evolved into
      coarse calcifications.

PMID- 7824371
TI  - Peristalsis in duplication cyst: a new diagnostic sonographic finding.
AB  - Ultrasonography is useful in the evaluation of enteric duplication cysts in
      infants. Typically, there is an anechoic fluid-filled lumen with a double-layered
      surrounding wall. This case report documents an additional sonographic finding
      which has not been recorded: peristaltic contractions of the cyst wall. This
      provides a real-time observation which is specific in the pre-operative diagnosis
      of neonatal cystic abdominal masses.

PMID- 7824372
TI  - Gastric duplication cyst in children: report of two cases.
AB  - Gastric duplication cysts (GDCs) in children are rare and are difficult to
      diagnose. They usually present as an epigastric mass but may be a chance finding.
      We report two cases and our experience with establishing the diagnosis.

PMID- 7824373
TI  - Intravesical oxybutinin chloride in children with intermittent catheterization:
      sonographic findings.
AB  - The sonographic findings in the bladder are presented in four children with
      myelomeningocele and neurogenic dysfunction of the bladder, who were treated with
      intermittent self-catheterization and intravesical oxybutinin chloride. All were
      referred for routine sonography of the urinary tract. Each had infused a crushed
      tablet of oxybutinin chloride intravesically 30-120 min before the examination.
      In two children, brightly echogenic, non-shadowing particles were suspended in
      the bladder urine. In one of these, the particles swirled giving the impression
      of a "snowstorm"; in the other, most of the particles gradually settled forming
      an irregular clump on the bladder base. In the remaining two children, the urine
      appeared diffusely hazy with innumerable tiny particles giving the impression of
      a fine mist filling the bladder. The sonographic appearance of the urine in the
      bladder after intravesical instillation of crushed tablets can be dramatic and
      can simulate pus, blood, fungus, or other debris in the bladder lumen. In the
      absence of clinical symptoms or hematuria, a history of recent infusion of
      medication into the bladder should be sought.

PMID- 7824374
TI  - Gold medalists. The Society for Pediatric Radiology 1994. Walter E. Berdon, MD.
      Scott Dunbar, MD.

PMID- 7824375
TI  - A sketch of man's efforts to mend his troubled mind.
AB  - People have sought comfort for their miseries and a cure for their troubles since
      prehistoric times. View the highlights of the story of psychiatry in this
      lightning tour of psychiatric history.

PMID- 7824376
TI  - Catharsis and abreaction in the history of psychological healing.
AB  - With roots in ancient religious practices of purification and cleansing and in
      ancient medicine's purgings, Plato evolved a verbal catharsis for diseases of the
      soul, and Aristotle developed a catharsis of the passions through tragic drama.
      Through the centuries, most cultures have had recognized contexts in which
      emotions were evoked, heightened in intensity, and ultimately released or
      discharged; and cathartic procedures can be detected in many cultures' healing
      practices. The late decades of the nineteenth century saw the emergence of
      numerous psychological healings with a cathartic basis. Catharsis came to mean
      the lively remembering of a traumatic experience in addition to the emotional
      release; and the term abreaction frequently was used to refer to the emotional
      release. Subsequently, the notion that the recovered traumatic memories needed to
      be integrated with the rest of the patient's mental life became a third
      significant element. The significance of these three factors has been debated
      vigorously; but, whether it has been some combination of them or merely the
      emotional discharge, there has been a cathartic element in many twentieth-century
      approaches to psychological healing.

PMID- 7824377
TI  - Punishment or therapy. Patients, doctors, and somatic remedies in the early
      twentieth century.
AB  - Although it has been argued that psychiatrists entered the modern era with the
      introduction of shock therapies and lobotomy in the 1930s and antipsychotic drugs
      in the 1950s, practicing psychiatrists of the 1910s and 1920s did not feel they
      were in the dark ages of therapeutics. These early twentieth-century
      psychiatrists had a variety of somatic remedies at their disposal. For example,
      they had a plethora of sedatives and hypnotic agents from which to choose,
      although these drugs too often produced troublesome side effects, and, from the
      point of view of these physicians, too closely resembled physical restraint in
      their effects on the patient. As we saw, physical restraint had a sullied
      reputation, psychiatrists believing it, at best, to be a necessary evil and not
      part of a therapeutic regimen. This did not mean psychiatrists felt helpless in
      treating insanity for they firmly believed that, unlike drugs and physical
      restraint, hydrotherapy acted therapeutically. Our examination of every-day
      treatment practices at Stockton and Patton state hospitals revealed that
      physicians found hydrotherapy to be a useful remedy on nearly all patients
      irrespective of diagnosis. The Agnews' investigation allowed us to examine the
      basic assumptions underpinning early twentieth-century therapeutics, and two
      major conclusions can be gleaned from this examination. First, how doctors
      perceive disease is inseparably linked to how they treat disease. In the case of
      hydrotherapy, physicians believed it effectively controlled their patients'
      behavior. To assert that it had therapeutic value and to differentiate it from
      mechanical restraint, however physicians transformed how they saw disease and
      therapy such that wrapping and bathing the "excited" and "frenzied" patients were
      therapeutic. Rather than seeing disruptive behavior as simply something in need
      of physical restraint, hydrotherapy allowed physicians to see these behaviors as
      the essence of disease and the primary object of their therapeutic ministrations.
      Second, patients' conceptions of disease and therapy may differ markedly from
      their physicians, which may be particularly true when disease is defined by
      visible behavior. At Agnews, patients spoke a different language than their
      physicians such that restraint differed little from therapy. In contrast to their
      doctors, patients were unable to see their behavior as necessarily pathologic,
      and, thus, were unable to recognize and to speak of the difference between
      mechanical restraint and hydrotherapy; both kinds of technologies simply
      restricted their bodily movements. With a different therapeutic practice such as
      malaria fever therapy, doctors and patients saw disease and its treatment in a
      new light.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7824378
TI  - A brief history of psychiatric classification. From the ancients to DSM-IV.
AB  - We are now at an interesting crossroads in the history of psychiatric nosology.
      There have been many oscillations over time between etiologic and descriptive
      models, between lumping and splitting, and between categorical and dimensional
      systems. It is unfortunate, but inevitable, that most of the etiologic models of
      the past have been based on unproven and unprovable theories. Like its
      predecessors, DSM-IV is a descriptive system, and it too gradually will be
      replaced by an etiologic model--one, it is hoped, that is more scientifically
      valid than previous attempts at etiologic explanation. This will be an important
      step for the profession, for scientific understanding, and for the patient.

PMID- 7824379
TI  - The treatment that will not die. Electroconvulsive therapy.

PMID- 7824380
TI  - History of the development of antipsychotic medication.
AB  - The story of the development of effective antipsychotic medications involves the
      collaboration of many people and organizations, ranging from Ayurvedic physicians
      to pharmaceutical companies, and the confluence of many quests, from that for
      improved synthetic dyes to that for an improved antimalarial agent. The disturbed
      behavior of patients and their evident anguish fueled the development of these
      drugs, which in turn has led to more research into the biochemistry of psychotic
      illnesses. Double-blind, placebo-controlled trials have established the true
      although partial utility of these new treatments. Most patients with
      schizophrenia--even those who have good responses to antipsychotic agents-
      continue to have some psychotic symptoms and to require a great deal of
      rehabilitation. It is hoped that physicians in the future will not find today's
      therapies as harmful as we find those of the past.

PMID- 7824381
TI  - Mad, homeless, and unwanted. A history of the care of the chronic mentally ill in
      America.
AB  - The history of the care and treatment of the mentally ill in America for nearly
      four centuries offers a sobering example of a cyclical pattern that alternated
      between enthusiastic optimism and fatalistic pessimism. In the nineteenth century
      an affinity for institutional solutions led to the creation of the mental
      hospital, an institution designed to promote recovery and to enable the
      individual to return to the community. No institution ever lives up to the claims
      of its promoters, and the mental hospital was no exception. Plagued by a variety
      of problems, its reputation and image were slowly tarnished. When it became clear
      that hospitals were caring for large numbers of chronic patients, the stage was
      set for an attack on its legitimacy after World War II. Its detractors insisted
      that a community-based policy could succeed where an institutional policy had
      failed, and that it was possible to identify mental illnesses in the early
      stages, at which time treatment would prevent the advent of chronicity. Between
      the 1940s and 1960s, there was a sustained attack on institutional care that
      finally succeeded when Congress enacted and the president signed a piece of
      legislation that shifted the locus of care and treatment back to the community.
      The community mental health policy proved no less problematic than its
      institutional predecessor. Indeed, the emergence of a new group of young chronic
      mentally ill persons in the 1970s and 1980s created entirely new problems, for
      the individuals who constituted this group proved difficult to treat and to care
      for under any circumstances. Each of these stages was marked by unrealistic
      expectations and rhetorical claims that had little basis in fact. In their quest
      to build public support and legitimate their cherished policy, psychiatric
      activists invariably insisted that they possessed the means to prevent and to
      cure severe mental disorders. When such expectations proved unrealistic, they
      placed the blame either upon callous governments, an uninformed public, or an
      obsolete system that failed to incorporate the findings of medical science. If
      American society is to deal effectively, compassionately, and humanely with the
      seriously mentally ill, several elements must be taken into account. First, the
      seriously mentally ill include individuals with quite different disorders,
      prognoses, and needs. Secondly, outcomes vary considerably over time. Some
      schizophrenics, for example, have reasonably good outcomes; others lapse into
      chronicity and become progressively more disabled. Finally, serious mental
      disorders are often exacerbated by poverty, racism, and substance abuse. Although
      psychiatric therapies can alleviate symptoms and permit individuals to live in
      the community, there is no "magic bullet" that will cure all cases of serious
      mental illnesses in the same way that antibiotic drugs are effective against
      acute infectious diseases.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7824382
TI  - Toward an intellectual history of transference. 1888-1900.
AB  - Freud's concept of transference was not the discovery of a solitary genius, but
      was an inspired, creative synthesis deeply rooted in the prevailing discourses of
      his time. In the nineteenth century, transference started out as a neurologic
      term; Freud used that concept of displaceable energies in his neurologic writings
      as early as 1888. Then in Studies in Hysteria, Freud explicated the basis by
      which ideas dissociated and made for a mesalliance with the physician. False
      connections such as transference were conceptualized along lines drawn by
      Charcot's school, and the concept of auto-suggestion that they used to explain
      the inherent suggestibility of a hysteric. In developing this 1895 model of
      transference, Freud strove to tame disquieting concerns about the epistemologic
      status of hysteria and hypnosis. It is the epistemologic anxiety created by
      accusations of iatrogenic suggestion as much as the sexual anxiety Szasz pointed
      to that prodded Freud to focus exclusively on the intrapsychic. It also may be
      the legacy of this epistemologic anxiety that accounts for the fact that until
      recently, psychoanalytic theoreticians have been hesitant to explore the effect
      that the real person of the analyst might have on the manifestations of
      transference. In the last years of the nineteenth century, Freud modified his
      theory of transference and built a place for it in his topographic model of mind.
      In the Interpretation of Dreams, Freud integrated the biologic and psychologic
      possibilities inherent in prior usages of ubertragung. By 1900, transference
      could theoretically refer to both a hypothesized displacement of quantifiable
      neuronal energies as well as the psychological phenomena Freud observed occurring
      between him and his patients. Perceptual theories of illusion like Helmholtz's
      provided Freud with a model that by analogy helped re-define transference as a
      central facet of irrational inner life. Transference in 1900 accounted for a
      patient's possible distortion of the person of the physician, but it also
      postulated a more general subjectification of consciousness and perception. In
      transference, a conscious perception could be as distorted by unconscious wishes
      as a day residue was in dreams. When Ida Bauer (a.k.a "Dora") stalked out of
      Freud's office, this newly empowered theory was in the metapsychological wings
      waiting to make meaning of her failed treatment. No longer was transference an
      unimportant mishap, a nuisance, or a theoretical aside. By 1900, transference was
      ready to stand, as it does today, at the core of psychoanalytic theory.

PMID- 7824383
TI  - Fact and fantasy in the history of Freud's views on incest and seduction.
AB  - This article surveys the history of Freud's attitudes and theories about the
      etiologic role of actual incest and seduction and neurosis. It also surveys the
      debate in historical writing on that topic, much of which oversimplifies complex
      and contradictory data. Here is an instance in which history is being written and
      used as part of current debates and polemics, principally to either
      monolithically defend or attack Freud. This article argues that Freud's motives
      for downplaying the etiologic role of seduction in the neuroses were complex, did
      not involve cowardice, and need to be understood both in terms of internal
      developments in Freud's thinking as well as in terms of relevant external (for
      example, historical) factors.

PMID- 7824384
TI  - The history of trauma in psychiatry.
AB  - The accidental separation of PTSD and the dissociative disorders, based on the
      unfortunate fact that the PTSD and the dissociative disorder workgroups of the
      DSM-III never met to compare data, and the lack of knowledge within the
      workgroups of existing research connecting these disorders, will continue in the
      DSM-IV. That separation, however, is slowly being eroded by a solid body of
      research that shows that these conditions rarely occur independently. Thus,
      contemporary research is beginning to show that the original concept of
      "hysteria," formulated 150 years ago to capture a group of patients who have
      complex psychological and somatic problems and whose problems often elude
      intervention from the medical and psychological professions, is alive and well
      among patients on the verge of the twenty-first century. Although the DSM process
      has attempted to create cleaner diagnostic categories, 100 years of research on
      traumatized patients consistently shows that these patients defy easy
      classification, and that they seem to have symptoms that represent somatic,
      social, symbolic, and intrapsychic adaptations to having experienced overwhelming
      terror. Thus, what the DSM split when it abolished hysteria as a diagnosis, has
      once again been found to constitute a syndrome, a conglomeration of symptoms,
      first defined by Briquet and Janet more than 100 years ago, which is the result
      of severe and prolonged interpersonal abuse, usually starting in childhood. One
      hundred years of research has shown us that patients often cannot remember and,
      instead, re-enact their dramas. The professions ministering to these patients
      have had similar problems with remembering the past, and thrice in this century
      have forgotten the hard-earned lessons from our patients. It is not likely that
      these amnesias and dissociations will be a thing of the past; they are likely to
      continue as long as physicians and psychologists are faced, helplessly, with
      man's inhumanity to man.

PMID- 7824385
TI  - A history of medical hypnosis.
AB  - From the origins of mysticism and theatrics, trivialized by stage performers,
      psychics, and charlatans, modern medical hypnosis has struggled to achieve and
      maintain a sense of professional integrity. Many of the principles of dynamic
      psychiatry are deeply rooted in the work of the early healers. Yet hypnosis as a
      clinical entity continues to fall in and out of favor over the years; again it is
      now being pushed beyond the limits of that which is reasonable and valid.

PMID- 7824386
TI  - The rebirth of forensic psychiatry in light of recent historical trends in
      criminal responsibility.
AB  - The forensic specialist's expertise lies in mapping the interaction of cognitive,
      affective, and physiologic processes as they affect and are affected by the
      choices people make, and in connecting this analysis with laws, legal criteria,
      and other standards. More simply and broadly, it lies in describing both the
      unique and the universal characteristics of any human being and distinguishing
      clearly between the two. This is a psychiatrist who conducts in a different
      arena, and from a more critical perspective, but for the same larger humane
      purpose, the in-depth journey into the self and its response to stress that is
      the essence of clinical practice.

PMID- 7824387
TI  - "What will happen if my Zurichers desert me?" The favorable reception of
      psychoanalysis in Switzerland.
AB  - Psychoanalysis has developed in a unique way in every country where it exists.
      This article discusses historical reasons for the favorable reception of
      psychoanalysis in Switzerland. Information is provided on the roles of
      psychiatrists, educators, and pastors in early twentieth century Swiss
      psychoanalysis. The factor of nationalism in the reception of psychoanalysis is
      emphasized. It is suggested that, in some countries, religion has played a
      positive role in the development of psychoanalysis.

PMID- 7824388
TI  - Between two wars. Psychoanalysis in Europe, 1918-1938.
AB  - In outline form, the major centers of European psychoanalysis have been
      described: from the first post-war meeting of the International Psychoanalytic
      Association in Budapest, 1918, when institutes for analytic training were
      proposed, to the Anschluss in March 1938, when Vienna was occupied by the Nazis
      and psychoanalysis on the Continent was extinguished for almost a decade. The
      emphasis has been on the organization and structure of institutes, chiefly
      Berlin, Vienna, and London, in that order. As an institutional history, both
      biographic details and theoretical issues have been kept to a minimum. The
      exceptions have been the controversies about lay analysis, Melanie Klein's
      developmental theories, and Ferenczi's innovations in technique. In these issues,
      some detail is necessary to understand how one institute differed from another
      within the analytic movement, although they were unified by the International
      Psychoanalytic Association (IPA). The history of the British analytic community,
      which survived World War II intact, is highly condensed, and Prague, Budapest,
      and Paris are briefly mentioned. A history of psychoanalysis in Russia has yet to
      be written, from its early flowering before and during the Bolshevik revolution
      (1918-1920) to its swift repression under Stalin in the later 1920s. Among the
      conclusions to be drawn from these data is the extent to which political events
      influenced the development of analysis, then in its most expansive phase. Even
      theory was affected by history, as in the evolution of Freud's repetition
      compulsion from observations on the traumatic neuroses of war. Socioeconomic
      conditions influenced the propagation of analytic ideas, favorably in post-war
      Berlin, adversely in Vienna. Each country evolved the kind of analysis that
      suited it best, with a variety of institutions within the same international
      movement. The causes of these variations in psychoanalytic institutes are a
      matter for speculation. Some analytic historians have linked Freud's advocacy of
      lay analysis to his estrangement from the medical establishment of Vienna, or to
      his dread that analysis might become the "house-maid" of medicine and psychiatry,
      as in America. Others find the roots of Freud's attitudes toward medicine in his
      conflicts about becoming a doctor, his yearning for philosophic speculation,
      which he "sternly held in check." In contrast, psychoanalysis in the United
      States was always committed to medical education as a prerequisite for becoming
      an analyst, and, in 1926, there was a sharp break from Freud's defense of lay
      analysis. Hale, among others, has suggested that the American "medical fixation"
      was a reaction to the chaotic state of our nineteenth century medical education,
      with diploma mills and self-taught healers scattered over a vast
      continent.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7824389
TI  - A history of psychiatric consultation in America.
AB  - Consultation-liaison psychiatry emerged in a particular socio-historical context,
      following a major shift of medicine into a more scientific, hospital-based
      system. Psychiatrists realized that they needed to move outside of the asylum and
      reintegrate themselves with the new structures of medicine, especially the
      general hospital and the medical school. Psychosomatic theory and psychoanalytic
      influence shaped the emergence of consultation-liaison activities in the 1930s
      through 1950s as they shaped most psychiatric services in the United States at
      that time, but they were an epiphenomenon to this powerful underlying dynamic
      that dictated psychiatry's move into the medical hospital. The experience of
      other countries tends to confirm this hypothesis, though a comparative history is
      limited by the strong postwar US influence. Pediatric consultation-liaison had a
      somewhat different evolution, reflecting the later emergence of pediatrics itself
      as a field and its strong psychosocial and preventive medicine emphasis.

PMID- 7824390
TI  - American psychiatry celebrates 150 years of caring.
AB  - One can see that the history of the American Psychiatric Association is the
      history of psychiatry and vice-versa. The last 150 years have seen significant
      advances in the humane treatment of the mentally ill. Stigma has been reduced,
      and significant numbers of patients are now leading productive and useful lives.
      One hundred and fifty years of caring, while commemorating our heritage, also
      challenges us to prepare for our future in our neverending quest for a cure.

PMID- 7824391
TI  - Antibiotic-containing implants.

PMID- 7824392
TI  - Broken screws.

PMID- 7824393
TI  - Risk factors for restricted motion after anterior cruciate reconstruction.
AB  - A retrospective review of 373 patients who had undergone anterior cruciate
      ligament (ACL) reconstruction utilizing the central third of the patellar tendon
      was undertaken to identify those factors that placed a patient at risk for
      restricted postoperative motion (flexion < or = 125 degrees or flexion
      contracture > or = 10 degrees). Stepwise logistic regression analysis determined
      that the variables most strongly correlated with restricted final range of motion
      (ROM) were open surgery (P = .0008) and reconstruction performed < or = 7 days
      after the initial injury (P = .004). Age, associated meniscal repair, or
      associated collateral ligament injuries did not significantly affect the ROM. A
      subgroup of 204 patients arthroscopically reconstructed more than 7 days post
      injury were significantly less likely to have limited motion when ROM exercises
      were begun within 2 days of surgery (P = .008). These data support delayed,
      arthroscopic ACL reconstruction followed by early ROM exercises as useful
      techniques for avoiding postoperative motion problems.

PMID- 7824394
TI  - Bone mineral content of the spine and proximal femur in female patients with hip
      fracture.
AB  - Measurement of bone density in the spine and hip by quantitative computed
      tomography (QCT) and dual photon absorptiometry (DPA) was performed in 36 women
      with hip fracture. Hip density by DPA was determined at three anatomic subregions
      of the hip. Comparison to normals revealed an average decrease in hip bone
      density by 15% below controls. Spine density measurements were not significantly
      different from that of controls. Correlations of hip and spine densities varied
      by hip subregion. This study demonstrated that bone density measurement methods
      and measurement at one axial site may not accurately reflect bone density at
      appendicular subregions.

PMID- 7824395
TI  - A new radiographic evaluation of primary osteoarthritis.
AB  - Two thousand five hip radiographs, both AP and lateral, were evaluated for
      osteoarthritis. We excluded all cases of traumatic osteoarthritis, rheumatoid
      arthritis, avascular necrosis, and congenital deformities. This left 1578 hips in
      1309 patients, which were sub-divided into three categories: medial
      osteoarthritis (405 hips, 20% of which were bilateral, 68% women, 32% men);
      superior lateral osteoarthritis (934 hips, 19% of which were bilateral, 49% men,
      51% women); and global osteoarthritis (239 hips, 23% bilateral, 53% men, 47%
      women). These categories may have significance in operative technique and
      survival of acetabular cups after total hip arthroplasty.

PMID- 7824396
TI  - Osteoporosis.

PMID- 7824397
TI  - Bilateral anterior dislocation of the shoulders with greater tuberosity
      fractures.

PMID- 7824398
TI  - Identification of acute pulmonary edema following routine outpatient orthopedic
      procedures in healthy, young athletes.

PMID- 7824399
TI  - Isolated middle finger complex dorsal dislocation of the metacarpophalangeal
      joint.

PMID- 7824400
TI  - Bilateral leg compartment syndrome complicating prolonged lithotomy position.

PMID- 7824401
TI  - Acetabular osteolysis in total hip arthroplasty: prevention and treatment.
AB  - Osteolysis can occur around loose, as well as well fixed, cemented or cementless
      acetabular components in total hip arthroplasty. Histologic studies of tissues
      biopsied from osteolytic regions suggest an adverse foreign body response to
      polyethylene and other particulate debris from prosthetic materials. Phagocytosis
      of these particles by macrophages and giant cells stimulate the production of
      proteolytic enzymes and inflammatory mediators, all leading to tissue
      destruction. The importance of polyethylene wear debris is now fully appreciated,
      and it is clear that this is the major contributor to particulate debris. The
      authors strongly recommend the avoidance of 32 mm femoral heads, thin acetabular
      component liners, titanium heads, and acetabular screws when absolutely
      necessary. We strongly advise 26 mm to 28 mm femoral heads, polyethylene
      thickness of at least 8 mm, precise liner shell contact, rigid fixation of the
      acetabular metal shell, intimate bone-acetabular shell contact, and
      circumferential porous coating of femoral components to decrease the amount of
      and migration potential of polyethylene debris (Table). Based on our current
      knowledge, these measures will minimize the problem of acetabular osteolysis.

PMID- 7824402
TI  - Radiologic case study. Plain film manifestations of ACL injury.
AB  - ACL injuries are common but often difficult to diagnose acutely by clinical
      examination alone. The Segond fracture, avulsion fracture of the anterior tibial
      spine, impacted lateral femoral condyle fracture, and fracture of the posterior
      lateral tibial plateau are radiographic signs often associated with ACL injury.
      It is important to recognize the significance of these subtle abnormalities and
      if found, further evaluation should be done to identify the presence and the
      extent of ACL injury as well as potential injury to other components of the knee
      joint. MRI is the imaging method of choice in these patients. Early diagnosis and
      treatment of knee joint abnormalities may help prevent or diminish long-term
      disability.

PMID- 7824403
TI  - Hyperthyroidism.
AB  - Hyperthyroidism in children and adolescents usually is due to Graves disease. The
      diagnosis may not be recognized promptly, and clinical findings initially may be
      attributed incorrectly to cardiac or psychological disorders. Once suspected,
      history and physical findings and measurements of TSH level, thyroid hormone
      levels, and thyroid antibodies make the diagnosis apparent. Treatment varies
      among endocrinologists and includes antithyroid medication, surgery, and
      radioactive iodine. Much is being learned about the autoimmune response that
      causes the disease, and the hope is that therapies directed at altering the
      autoimmune abnormalities ultimately will offer the best therapeutic alternatives.

PMID- 7824404
TI  - Neonatal jaundice.

PMID- 7824405
TI  - Quality improvement: an ACQIP exercise on vaccine administration: subscriber
      responses and recommendations.

PMID- 7824406
TI  - Cardiac arrhythmias.

PMID- 7824407
TI  - Antibiotics: mechanisms of action.
AB  - Medical practice rests on the foundation of science. Clinicians are constantly
      making practical decisions and dealing with immediate situations that demand
      solutions. Time should be taken to focus on those scientific principles that
      underlie our diagnostic and therapeutic maneuvers. This section of Pediatrics in
      Review presents selected topics that are relevant to practice from the areas of
      physiology, pharmacology, biochemistry, and other disciplines; clarification of
      these will augment the pediatrician's understanding of clinical procedures.

PMID- 7824408
TI  - Psychosomatic disorders: the approach.

PMID- 7824409
TI  - Malaria in the liver.

PMID- 7824410
TI  - Neurogenic thoracic outlet syndromes.

PMID- 7824412
TI  - Osteoporosis and genetic influence: a three-generation study.
AB  - We have studied 27 triads of mother, daughter and grandmother for possible
      genetic influence on distal and proximal forearm bone density, measured by single
      photon absorptiometry. We found a significant correlation of bone density at the
      proximal forearm between the mothers and grandmothers (r = 0.499, P < 0.01).
      There was also a weak correlation between proximal forearm bone densities of
      mothers and daughters (r = 0.327, P < 0.1). Significant correlations were found
      between the three generations for grip strength, pedometry, height and triceps
      skinfold thickness. There was also significant correlation between mother and
      grandmother for alcohol intake. There was no correlation for contraceptive pill
      use, smoking, dietary calcium intake, body weight or body mass index. The study
      concludes that, although there are similarities in bone mineral content between
      the three generations, genetic factors cannot be conclusively proven to be the
      major determinant of bone density. Lifestyle and environmental factors may have a
      bearing on achieving the peak bone mass and subsequent development of
      osteoporosis.

PMID- 7824411
TI  - The management of pregnancy in hypertensive patients.

PMID- 7824413
TI  - Haemodynamic and oxygen transport response during exchange transfusion for severe
      falciparum malaria.
AB  - We describe the haemodynamic and oxygen transport response in a patient
      undergoing exchange transfusion for severe falciparum malaria. We found that
      exchange transfusion produced a significant increase in left ventricular stroke
      work index, systemic oxygen delivery and oxygen consumption. This potentially
      beneficial effect of exchange transfusion has not been reported previously.

PMID- 7824414
TI  - Creatine kinase isoform electrophoresis for the early confirmation of myocardial
      infarction detected by timed sequential CK slope analysis.
AB  - Creatine kinase (CK)-MM and -MB isoforms were evaluated for the early diagnosis
      of myocardial infarction in patients aged over 65 years admitted to a district
      general hospital with acute chest pain. Samples were collected for standard
      cardiac enzymes, timed CK slope analysis, and CKMM and CKMB isoform analysis from
      48 patients admitted with acute chest pain. CKMM and CKMB isoform analyses were
      conducted using a Helena Rep electrophoresis system under standard conditions
      supplied by the company. In addition to the results of the biochemical tests the
      discharge diagnosis of the patients were also recorded. CKMM isoform analysis
      resulted in three false-negative classifications of patients and one false
      positive. The predictive value of this test was 100% for a positive result and
      94% for a negative result. CKMB isoform analysis was less accurate and there were
      six false-negative results and five false-positive results. The predictive value
      of a positive result was 75% and 85% for a negative result. CK isoform analysis
      became unreliable when mean total CK levels in serum were 210 IU/l (+/- 171). CK
      isoform analysis may be of use in the investigation of patients whose samples
      have a total CK concentration greater than the reference range but was no better
      than timed CK slope analysis for the detection of myocardial infarction in
      patients aged more than 65 years.

PMID- 7824415
TI  - Possible role of Helicobacter pylori serology in reducing endoscopy workload.
AB  - We validated a commercial enzyme-linked immunosorbent assay (ELISA), Helico-G, in
      diagnosing H. pylori in 129 patients (mean age 50 years, range 15-86). We
      analysed the results of endoscopy against serology to see whether there was a
      possibility of adopting the strategy of not endoscoping dyspeptic subjects under
      the age of 45. H. pylori infection was considered present if either histology
      and/or culture were positive. The ELISA had a sensitivity of 88%, specificity of
      72%, positive predictive value of 85%, negative predictive value of 77% and
      accuracy of 82% in detecting H. pylori. In a subgroup of 52 subjects aged 45 or
      less (mean age 35 years, range 15-45), 17 out of 25 patients with positive
      endoscopic findings were H. pylori seropositive while 16 out of 27 patients had
      normal endoscopic findings. Eighteen out of the 52 patients (35%) were H. pylori
      seronegative and normal endoscopically except for five patients (10%) who had
      mild to moderate oesophagitis and two who had non-erosive gastritis (4%). All
      patients with duodenal ulcer disease (7) were seropositive giving predictive
      values of positive and negative serology for a diagnosis of duodenal ulcer
      disease as 28% and 100%, respectively. Therefore adopting a strategy of
      endoscoping subjects under the age of 45 only if they were H. pylori seropositive
      would have saved 35% of endoscopies in this age group but missed oesophagitis in
      10%. Negative serology would tend to exclude duodenal ulcer disease while
      positive serology discriminates poorly for it. Serology may be a useful adjunct
      in screening to reduce endoscopy workload provided that patients with gastro
      oesophageal reflux symptoms are excluded.

PMID- 7824416
TI  - Living wills: would sick people change their minds?
AB  - Patients admitted acutely to a geriatric medical unit were interviewed on
      admission about their opinions on cardiopulmonary resuscitation (CPR). They
      underwent a general examination and their mental health was documented by
      completing the geriatric depression scale. Those who did not wish CPR in the
      event of a cardiac arrest were questioned again on recovery. Of 216 patients
      admitted, only three objected to answering the questions and after the other
      exclusion criteria were applied, 100 patients were included in the study. A total
      of 92% of patients wished CPR in the event of a cardiac arrest. The 8% who did
      not wish CPR contained more people scoring high on the geriatric depression
      scale. After recovery, three of that eight had changed their minds and wished CPR
      if required. Patients who are acutely unwell may make decisions that are
      influenced by their condition at this point in time and it is important to
      recognize that these decisions may not be maintained. In this study, consultant
      geriatricians did not reflect their patients' desires in making decisions about
      who should receive CPR if required.

PMID- 7824417
TI  - Aortic dissection complicated by a mediastinal haematoma and haemoptysis.

PMID- 7824418
TI  - Pseudobulbar palsy associated with trismus.
AB  - A 60 year old patient presented with an acute pseudobulbar palsy associated with
      trismus. A computed tomography scan revealed low attenuation areas consistent
      with infarction affecting the genu of the internal capsules bilaterally. Trismus
      has not previously been described as the presenting feature of a pseudobulbar
      palsy.

PMID- 7824419
TI  - Severe hypophosphataemia in anorexia nervosa.
AB  - In addition to well-described acid-base and electrolyte disturbances, anorexia
      nervosa may be complicated by severe hypophosphataemia. We report a case of
      anorexia nervosa complicated by life-threatening hypophosphataemia manifesting as
      generalized muscle weakness and bulbar muscle dysfunction, resulting in an
      aspiration pneumonia and cardiorespiratory arrest.

PMID- 7824420
TI  - Genetic analysis in a female manifesting haemophilia B.
AB  - A 5 year old female child presented with a psoas haematoma as the first
      manifestation of haemophilia B. Molecular genetic studies were performed to
      investigate the inheritance of the disorder and the mechanisms by which females
      may express the haemophilia B phenotype are discussed.

PMID- 7824421
TI  - Hyponatraemic rhabdomyolysis in Addison's disease.

PMID- 7824422
TI  - Myositis and eosinophilia in a patient with sarcoidosis.
AB  - We present a patient with muscle manifestations of sarcoidosis associated with
      raised creatine kinase levels, eosinophilia and interstitial lung disease. She
      had significant improvement on prednisolone 30 mg per day.

PMID- 7824423
TI  - Endocrine assessment of impotence--pitfalls of measuring serum testosterone
      without sex-hormone-binding globulin.
AB  - The pitfalls of measuring only total serum testosterone are illustrated by a 52
      year old man whose hyperprolactinaemia was associated with normal total serum
      testosterone but a raised sex-hormone-binding globulin, giving a low free
      testosterone. Prolactin suppression with bromocriptine normalized sex-hormone
      binding globulin and free testosterone, and restored potency and energy after 30
      years of impotence and tiredness.

PMID- 7824424
TI  - 45,X Turner syndrome with normal ovarial function and multiple malformations of
      the aorta.
AB  - We present a case of a female patient with monosomy of X chromosome in peripheral
      lymphocytes and skin fibroblasts, normal ovarian function and associated multiple
      congenital abnormalities of the aorta: bicuspid aortic valve, dilatation of the
      ascending aorta and multiple cystic structures of the aortic wall, complicated by
      endarteritis. We review the literature on fertile women with 45,X karyotype and
      the possible pathogenetic mechanisms of the aortic defects described as 'cystic
      medial necrosis of the aorta'.

PMID- 7824425
TI  - The use of capsaicin cream in a case of erythromelalgia.
AB  - We present a case of erythromelalgia in a 68 year old lady who responded, within
      48 hours, to a twice daily topical application of capsaicin cream 0.025%.
      Capsaicin cream was stopped after 2 months, and 6 months later the patient
      continued to have the symptomatic relief she experienced initially.

PMID- 7824426
TI  - Stridor, the presenting symptom of a thyroid abscess.

PMID- 7824427
TI  - Drop attacks in the elderly: effect of pyridostigmine.

PMID- 7824428
TI  - Splenic abscess due to Eikenella corrodens.

PMID- 7824429
TI  - Acute serum lipid changes in a renal transplant recipient on intravenous
      cyclosporin upon administration of an intravenous lipid solution.

PMID- 7824430
TI  - Rhabdomyolysis and renal failure following defibrillation.

PMID- 7824431
TI  - [Prospective study of maternal behavior in the neonatal period: a pilot study].
AB  - This study intends to test empirically some pre- and perinatal conditions of
      loving motherly behavior and motherly anxiety during the first month after birth.
      In the framework of a prospective study a sample of 40 women, pregnant for the
      first time, was tested by a questionnaire in the last trimester of pregnancy.
      They were visited in their homes about 19 days after having given birth. There
      loving behavior during nursing was observed. Their anxiety was credited by a
      structured interview. When considering the single postulated predictors
      separately a significant prediction of the observed loving behavior was only
      possible by the frequency of their attempts to establish a contact with the
      unborn. This predictor was able to explain one third of the variance. If all the
      relevant predictors were considered, two fifth of the loving behavior could be
      explained. It was clearly confirmed that the experience of a direct sensual and
      physical contact was most important for the continuity of a loving relationship
      with the child while the cognitive engagement was far less important. Personality
      characteristics like emotional lability and anxiety proved to be significant
      correlates of early maternal anxiety, thus confirming once again the relevance of
      stable personality characteristics for motherly behavior.

PMID- 7824432
TI  - [Incidence and persistence of problems at sleep onset and sleep continuation in
      the preschool period: results of a prospective study of a representative sample
      in Bavaria].
AB  - The prevalence and persistence of sleeping problems was studied in a prospective
      investigation of a representative sample of 432 German children at the ages of 5,
      20 and 56 months. 21.5% of children had night waking problems at 5 months, 21.8%
      at 20 months and 13.3% at 56 months. Falling asleep difficulties were diagnosed
      in 12.1% of 4-5 year olds. One in four of five year-olds slept regularly in the
      bed with the parents (co-sleeping). Children with night waking problems had a 2.2
      to 2.5 fold increased risk to remain nightwakers from one assessment point to the
      next compared with non-wakers. 7 to 14% of parents were distressed by their
      children's sleeping behaviour. Parental behaviour often contributed to continued
      sleeping problems because the children were not supported in acquiring
      appropriate skills to settle to sleep unaided. A developmental model for the
      treatment of sleeping problems is discussed.

PMID- 7824433
TI  - [Attachment and identity of adoptive children].
AB  - At first the development of the mother-child-attachment is discussed on the basis
      of the theories of Bowlby and Ainsworth. A study by one of the Dutch authors
      (Juffer) is described, in which the quality of the attachment was assessed in 90
      foreign adoptions and in which a positive impact of interventions (booklet,
      discussion of videotapes) on the quality of the attachment was found. Then the
      relationship between adoptees and their biological parents is discussed. The
      consequences of the "double parenthood" for the identity development of adopted
      children is described.

PMID- 7824434
TI  - [Mother-infant relations: beginnings of the psychological structure].
AB  - The practice of joint mother-infant psychotherapy is a good setting for studying
      parental contributions to the formation of the child's psychic structure. Parents
      organize their infant's experience in terms of their own cognitive and emotional
      predilections. Through projective identifications they lend meaning to the
      infant's behaviors and attitudes. We are presenting two cases where one can
      witness the production of shared interactive scenarios between mother and child.
      In the first case a mother constantly interferes with the alimentary initiative
      of her baby, as if she wanted to control the baby's impulsive oral demands. In
      the second case mother defines the child's solicitations in terms of aggressive
      intentions. Those two cases are used as illustration of the powerfully impact of
      maternal predilection and aversion onto the development of expressions and
      controls in the infant. The general topic of this paper is communication between
      mother and infant and the transmission of values and attitudes through behaviors
      from mothers to babies.

PMID- 7824435
TI  - [Vascular tumors of the skin and soft tissue. Overview of newly characterized
      entities and variants].
AB  - This review summarizes vascular tumours of skin and soft tissues that have been
      characterised in recent years. Although most of them are very rare, knowledge
      about their reproducible clinicopathological features is important to avoid
      diagnostic pitfalls. These lesions include: bacillary angiomatosis, a
      vasoproliferative, pseudoneoplastic infection of immunocompromised patients
      caused by Rochalimaea henselae; tufted angioma, a variant of lobular capillary
      haemangioma characterised by a "cannon-ball" distribution of multiple lobules
      composed of packed capillaries and pericytes; microvenular haemangioma, a
      cutaneous haemangioma composed of thin-walled and irregularly branching blood
      vessels which dissect dermal collagen; sinusoidal haemangioma, a distinctive
      variant of cavernous haemangioma which may be located in the subcutaneous breast
      tissue and then may be confused with well-differentiated angiosarcoma; "hobnail
      haemangioma" (targetoid haemosiderotic haemangioma), a benign vascular tumour
      with a distinctive clinical targetoid appearance and a hobnail cytomorphology of
      the prominent endothelial tumour cells; retiform haemangioendothelioma, a very
      recently characterised low-grade angiosarcoma occurring most commonly in the
      extremities of adolescents which is characterised by arborising blood vessels
      arranged in a retiform pattern and lined by hobnail-like prominent endothelial
      cells; Kaposi-like infantile haemangioendothelioma, a borderline malignant tumour
      of infants mimicking Kaposi's sarcoma histologically; epithelioid angiosarcoma, a
      highly aggressive tumour in the spectrum of epithelioid vascular lesions which
      stains positively for endothelial and epithelial immunohistological markers;
      benign lymph-angioendothelioma (progressive lymphangioma), a benign, slowly
      growing macule or plaque which has to be distinguished from well-differentiated
      angiosarcoma and Kaposi's sarcoma; and lymphangiomatosis of the limbs, a poorly
      recognised angiomatosis occurring in young patients and limited mainly to the
      limbs with a favourable prognosis.

PMID- 7824436
TI  - [The cancer cell and the connective tissue. A historical retrospect].
AB  - Since the introduction of microscopic examination of tumours, many researchers
      have dealt with the relationship between cancer cells and connective tissue.
      Rudolf Virchow's opinion that carcinomas derive from connective tissue was soon
      disproved by the studies of Cornil, Thiersch, and Waldeyer, but no clue was
      provided to the reason for the invasion of the epithelium. Julius Cohnheim and
      particularly Hugo Ribbert were of the opinion that invasion of the epithelium was
      only possible in the case of a primarily altered connective tissue. Ultimately
      the stroma determines malignant growth. From 1902, Max Borst finally formulated
      the views on tumour-stroma-relationship that are still valid today and postulated
      interrelations which can only be proved and confirmed by modern molecular
      biological methods.

PMID- 7824437
TI  - [Clinical pathology of inverted papillomas of the urinary bladder. A complex
      morphologic and catamnestic study (2)].
AB  - The histopathology, ultrastructure, pathological status and clinical course are
      described in a total of 29 cases of inverted papilloma of the urinary bladder
      (IP). The IP was isolated in 16 cases and occurred in combination with a
      papillary urothelial carcinoma in 13 cases. Histologically, a trabecular, a
      glandular and a mixed type can be differentiated. The trabecular form
      predominates in a ratio of 4:1. The glandular form is further subdivided into a
      cystic form and an adenomatous form containing cylindrical cells. Contrary to
      earlier assumptions, dysplasia and malignant transformation also occur in IP.
      Amongst the 16 isolated IP observed, four showed slight and four showed moderate
      dysplasia. One isolated IP was malignant and invasive. In IP in combination with
      papillary urothelial carcinomas, malignant transformation is somewhat more
      frequent. Four malignant IP and up to 85% dysplasias were found among the 13
      cases. The ultrastructure of IP reveals two cell types: a light cell form which
      corresponds to a slightly dysplastic urothelium and a darker cell form with or
      without microvilli which is observed in the glandular type. A frequent
      characteristic is a thickening of the basement membrane besides abundant "tight
      junctions". The immunohistochemistry is relatively uncharacteristic. This also
      applies to the blood group isoantigens, which showed irregular and relative
      uninformative results in the SCRA test. IP is observed in all age groups and the
      sex ratio (M/F) is 3:1. The average age of manifestation is 56 years, about 10
      years earlier than bladder carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7824438
TI  - [Cytogenetics in addition to histopathology exemplified by myelodysplastic
      syndrome].
AB  - The value of cytogenetics performed simultaneously with histopathology was
      evaluated in patients with myelodysplastic syndrome (MDS). Clonal karyotype
      changes of the bone marrow cells supporting the histological diagnosis were found
      in 38/69 cases (55%). The chromosome aberrations, especially complex changes,
      were significantly correlated to distinct histopathological findings such as
      atypias of the haematopoietic cell lines and myelosclerosis. Complex karyotype
      changes were further associated with short survival of the MDS patients. Our
      results demonstrate that cytogenetic analyses are helpful in supplementing the
      histopathological diagnoses. Recent developments in molecular cytogenetics even
      allow the detection of chromosomal aberrations in non-dividing cells from
      cytological preparations or tissue sections which may become available for
      routine diagnosis.

PMID- 7824439
TI  - [Morphology of bone marrow in systemic lupus erythematosus].
AB  - Autoimmune-mediated cell destruction in peripheral blood has been considered the
      most frequent cause of cytopenias seen in systemic lupus erythematosus. On the
      other hand, several bone marrow abnormalities have been documented by case
      reports as well as retrospective studies. In the present prospective analysis we
      addressed the question of the frequency and features of bone marrow abnormalities
      in SLE patients presenting peripheral blood cytopenias. In 12 of the 21 patients
      examined, we found foci of an exudative necrotic reaction characterized by edema,
      necrotic cells (nucleophagocytosis) and an infiltrate by lymphocytes, plasma
      cells and macrophages. Reticulin fibers were increased in these foci in 8 cases.
      Surprisingly, hemopoiesis was hyperplastic in only 6 patients, but was grossly
      diminished in 12 cases. In 14 patients atypical elements of one or more cell
      lines could be observed. Most commonly (11 cases), an increase in megakaryocytes
      with atypical elements showing small pleomorphic nuclei could be seen, together
      with normal nuclei. Cell atypia in the erythroid line was found in 8 cases, and
      abnormal granulocytic precursors were seen in 3 cases. No ring sideroblasts could
      be observed in any case. All these features provide persuasive evidence that the
      bone marrow is a common target organ affected by autoaggression in SLE. Central
      and peripheral mechanisms acting to produce peripheral cytopenias must be assumed
      in most cases.

PMID- 7824440
TI  - [Micro-callus formation of spongiosa. An up to now underestimated repair
      mechanism of the skeletal system].
AB  - Microcallus formations are demonstrable in nearly all cancellous bones by means
      of suitable preparation techniques. Histologically, these structures are immature
      fibrous bone formed in local overloaded parts of the trabeculae. Using a
      preparation technique that allows combined two- and three-dimensional analysis,
      26 normal human spines and 11 osteoporotic spines were investigated for
      microcallus. Microcallus formations occur frequently in people over 45 years of
      age. They are mainly localized in the lower thoracic and lumbar spine and occur
      significantly more frequent in females than in males. The number of microcallus
      formations depends more on the microarchitecture of the cancellous bone than on
      individual trabecular parameters. In about 33% of cases microfractures are
      demonstrable in the centre of the microcallus formation. In non-invasive studies
      the bone mass could be misinterpreted due to microcallus. Although it indicates
      instability of the bone structure, microcallus formation is not a purely negative
      mechanism. It stabilizes and regenerates the bone tissue. Furthermore, complete
      new trabeculae can be formed due to bridges of microcallus between residual
      trabeculae. Osteoporosis is not the result of an inability to form microcallus.

PMID- 7824442
TI  - [MALT lymphoma/Hodgkin's disease].

PMID- 7824441
TI  - [Leiomyosarcoma in the thyroid gland--primary tumor or metastasis?].
AB  - In a 69-year-old female patient a moderately pleomorphic spindle-cell thyroid
      tumour measuring 5 cm in diameter was initially misinterpreted as primary
      anaplastic thyroid carcinoma. During clinical investigations to elucidate the
      cause of severe anaemia, 17 months later an ulcerated duodenal leiomyosarcoma was
      detected and removed by duodenopancreatectomy. Reevaluation of the thyroid nodule
      led to revision of the initial diagnosis to metastatic leiomyosarcoma. Six months
      later the patient died from cerebral stroke. Autopsy findings confirmed the
      diagnosis of primary leiomyosarcoma of the duodenum with initial manifestation as
      thyroid metastasis.

PMID- 7824443
TI  - Current topic: the role of amniotic endothelin in human pregnancy.
AB  - Endothelin (ET), a potent vasoconstrictor peptide, was originally isolated from
      culture medium of porcine aortic endothelial cells. Subsequently, ET was also
      reported to be produced by non-vascular tissues, and to be involved in various
      biological phenomena in these tissues. Recently, a high concentration of ET-1
      like immunoreactivity (ET-1-LI) was detected in human amniotic fluid. Amnion
      tissue also contained a large amount of ET-1-LI, and cultured amnion cells
      secreted large amounts of ET-1-LI. The major component of ET-1-LI in these
      samples was ET-1. Moreover, the expression of prepro-ET-1 mRNA was detected in
      both amnion tissue and cultured amnion cells, indicating that ET-1 in the
      amniotic fluid originated from amnion cells. In addition, specific receptors for
      ET were detected in myometrium, decidua vera, chorion laeve and placenta, by both
      ligand binding analysis and Northern blot analysis. These findings suggest that
      ET-1 secreted from amnion cells plays a physiological role in human pregnancy. In
      this paper, the regulation of ET-1 production and expression of ET-receptors in
      avascular human amnion tissue are reviewed. The possible importance of amniotic
      ET in human pregnancy is also discussed.

PMID- 7824444
TI  - Differential responses of phenotypically distinct rat trophoblast cell lines to
      MHC class I antigen-inducing cytokines.
AB  - Phenotypically distinct rat trophoblast cell lines, the Rcho-1 and R8RP.3 cells,
      were compared for their responses to cytokines known to induce major
      histocompatibility (MHC) class I antigens, tumour necrosis factor (TNF),
      transforming growth factor-beta (TGF-beta), and interferon-gamma (IFN-gamma).
      Cell enzyme immunosorbent assays and flow cytometry experiments showed that only
      IFN-gamma could induce RT1 class I antigens on the Rcho-1 cells. Non-adherent
      cells were slightly less responsive than adherent, giant cell-like Rcho-1 cells.
      By contrast, RT1 class I antigens on the R8RP.3 cells were induced by both TGF
      beta 1 and IFN-gamma. The cytokines also had different effects on mitochondrial
      enzyme activity in the two lines. TNF and TGF-beta 1 mRNAs were demonstrated in
      both lines by using Northern blot hybridization. Rcho-1 but not R8RP.3 cells
      contained two TNF messages (approximately 2.2, 1.9 kb). Steady state levels of
      transcripts from the TNF gene, and, to a lesser extent, the TGF-beta 1 gene, were
      increased in cultures of Rcho-1 cells that contained high proportions of giant
      cells. Thus, phenotypically distinct rat trophoblast cell lines do not respond
      identically to TNF, TGF-beta 1 or IFN-gamma, transcription of cytokine genes does
      not prevent the cells from responding to paracrine cytokine signals, and the
      cells contain novel TNF transcripts that might be important in cell maturation or
      differentiation.

PMID- 7824445
TI  - Immunosuppressive effects of human placental trophoblast interferon-beta on
      lymphocytes in vitro.
AB  - Human placental trophoblast cells produce predominantly interferon-beta-type (IFN
      beta) when stimulated with viral inducers. The aim of the present study was to
      determine the in vitro antiproliferative effect of the trophoblast interferon
      beta (tro-IFN-beta) on mitogen-stimulated and resting lymphocytes. The
      antiproliferative effect of the tro-IFN-beta was compared to human recombinant
      IFN-beta. All activities of tro-IFN-beta and human recombinant IFN-beta ranging
      between 10-1000 IU/ml showed suppression of proliferative responses on mitogen
      stimulated and resting lymphocytes compared to cultures without IFN treatment.
      The inhibitory level of both tro-IFN-beta and recombinant IFN-beta was
      significantly higher on the stimulated than on the resting lymphocytes. Although
      there was a variation in the inhibition of lymphocyte proliferation by both IFNs
      with respect to time, there was no statistically significant difference in the
      antiproliferative effect of the IFNs on both resting and mitogen-stimulated
      lymphocytes. Since IFNs are produced locally by the placenta during pregnancy,
      our data suggest that in addition to the antiviral activity, the human tro-IFN
      beta may participate in the local control of the maternal immune response during
      pregnancy at the fetomaternal interface.

PMID- 7824446
TI  - The expression of the placental anticoagulant protein, annexin V, by villous
      trophoblasts: immunolocalization and in vitro regulation.
AB  - We evaluated the histological and ultrastructural localization of the potent
      anticoagulant protein, annexin V, at the light and electron microscopic levels,
      using immunohistochemistry and an immunogold method. Annexin V was found to
      localize to the microvillar surface of the villous syncytiotrophoblasts. Isolated
      villous-derived trophoblasts were then utilized to evaluate the expression of
      annexin 1 protein mRNA in response to syncytialization in vitro, as well as to
      exposure to adenylate cyclase and protein kinase C agonists. Levels of
      immunoreactive annexin V released into the conditioned media and associated with
      cell protein were assessed by ELISA while levels of annexin V mRNA were evaluated
      by Northern analysis. No significant change in either media or cell-associated
      annexin V concentrations were detected over time in culture or in response to 1.5
      mM 8-bromo-cyclic-adenosine-monophosphate (8-b-cAMP) or 0.15 nM phorbol ester
      myristic acid (PMA). These results indicate that annexin V is ideally positioned
      to inhibit intervillous thrombosis and maintain the fluidity of the intervillous
      circulation. Moreover, the absence of trophoblast annexin V regulation by
      intracellular second messenger regulators suggests that this crucial placental
      anticoagulant factor is constitutively produced.

PMID- 7824447
TI  - Onset and distribution of factor XIII-containing cells in the mesenchyme of
      chorionic villi during early phase of human placentation.
AB  - To learn more about the distribution and possible function of factor XIII (FXIII)
      containing cells of human placenta, paraffin embedded and frozen sections of
      placenta samples from the first trimester of pregnancies--terminated by legal
      abortions--were studied by single and double labelling immunomorphological
      techniques. It was observed that at the fifth gestational week in the chorionic
      mesenchyme, FXIII-containing small mononuclear, round shaped cells start to
      appear. The relative amount of the FXIII-containing cells rapidly increased up to
      the seventh gestational week, reaching nearly 30 per cent of all mesenchymal
      cells. Simultaneously these cells differentiated into large stellate cells having
      numerous vacuoles in their cytoplasm. These cells were characterized in double
      labelling experiments and proved to be macrophages (CD 14+, KiM7+, labelled with
      antimacrophage monoclonal antibody). In the fifth-seventh weeks of gestation,
      these cells were homogenously scattered in the immature mesenchymal connective
      tissue, but from the eight gestational week they tended to accumulate in the
      peripheral part of chorionic villi while the central mesenchyme showed intense
      fibrotic changes. The abundance and characteristic distribution of the FXIII
      positive macrophages in the chorionic mesenchyme during the first trimester of
      pregnancy suggest that these cells may have an active role in the formation of
      connective tissue in the early phase of placentation.

PMID- 7824448
TI  - Pregnancy-associated major basic protein: deposition of protein and expression of
      mRNA at the maternal-fetal junction in early and late gestation.
AB  - Pregnancy-associated major basic protein (pMBP) has previously been isolated from
      human placenta and localized to the X cell. Here we used immunofluorescence
      staining and in situ hybridization to determine the distribution of pMBP and pMBP
      mRNA throughout the maternal-fetal junction in both early gestation tissues and
      at term. In early gestation tissues, pMBP was present only at the placental
      insertion site. Specifically, pMBP was present in (a) the decidua basalis (in the
      extracellular space, in interstitial pools and inside endometrial glands) and (b)
      intracellularly within extravillous interstitial trophoblasts in the decidua, in
      the myometrium and surrounding but not within luminal cells of spiral arteries.
      At term, the placental bed showed intense extracellular pMBP staining with little
      intracellular pMBP. In situ hybridization showed the presence of pMBP mRNA in
      both the early and late gestational tissues. pMBP mRNA was present in cells in
      the decidua, at the decidual-myometrial junction and in cell islands.
      Quantitative image analysis showed statistically significant hybridization
      signals with the pMBP antisense probe as compared to the control/sense probe.
      These results indicate that pMBP mRNA is expressed and pMBP is extensively
      deposited at the maternal-fetal junction in early pregnancy and at term.

PMID- 7824449
TI  - Binding of insulin-like growth factor I to human trophoblast cells during
      differentiation in vitro.
AB  - The binding of insulin-like growth factor I (IGF-I) to its receptor stimulates
      cell proliferation and differentiation in several cell systems. In the present
      studies, we have characterized the expression of IGF-I receptors during
      trophoblast differentiation in vitro. During differentiation of cytotrophoblast
      cells to syncytiotrophoblasts, IGF-I binding capacity increased 40 per cent from
      80 to 130 fmol/mg protein on day 1 to day 2, then decreased by 70 per cent from
      130 to 40 fmol/mg protein on day 2 to day 3. IGF-I binding affinity increased non
      significantly with a change in kDa from 6.5 to 3.5 nM between day 1 and day 3 in
      culture. In contrast, when cells were maintained in an undifferentiated state,
      there was no change in either binding capacity or affinity over three days in
      culture. Down-regulation of the IGF-I receptor by pre-incubation with IGF-I was
      demonstrated for syncytiotrophoblasts with a maximum decrease in IGF-I binding of
      67 per cent after 72 h pre-incubation. Minimal down-regulation was seen for the
      cytotrophoblast cells (maximum decrease in IGF-I binding of 22 per cent after 48
      h pre-incubation). In conclusion, these results demonstrated that IGF-I binding
      to the trophoblast cell surface changes during trophoblast differentiation in
      vitro and suggest involvement of IGF-I in this process.

PMID- 7824450
TI  - Immunohistochemical localization of parathyroid hormone-related protein (PTHrP)
      in human term placenta and membranes.
AB  - Parathyroid hormone-related protein (PTHrP), the major factor responsible for
      hypercalcaemia of malignancy, is widely expressed in normal adult and fetal
      tissues. In this study, the distribution of PTHrP was examined in human term
      placenta and membranes by immunohistochemistry using antisera to PTHrP 1-34 and
      37-67. PTHrP was detected in cuboidal epithelial cells of amnion and in
      cytotrophoblastic cells of chorionic laeve and adherent maternal decidua. In
      placenta, PTHrP 1-34 was detected in the syncytiotrophoblast, while PTHrP 37-67
      activity was mainly present in the brush border of the syncytiotrophoblast. This
      study also identified PTHrP 37-67 associated with fetal vessels of placental
      villi. These findings may reflect the cellular distribution of intact PTHrP or
      sub-fragments derived by post-translational processing. Postulated actions of
      PTHrP in the uteroplacental unit include transport of calcium across the
      placenta, stretch of membranes, inhibition of uterine contractility, growth and
      differentiation, and vasoregulation.

PMID- 7824452
TI  - A comparison of granulated metrial gland cells with Kurloff cells in the guinea
      pig.

PMID- 7824451
TI  - Expression of two alpha 2-adrenergic receptor subtypes in human placenta:
      evidence from direct binding studies.
AB  - Adrenergic receptors may play an important role for mediating a variety of
      metabolic and haemodynamic effects of catecholamines including placental blood
      flow. The alpha-adrenergic receptors of the human placenta were characterized in
      vitro by the use of [3H]rauwolscine and [3H]prazosin as radioligands. Saturation
      experiments would suggest that the alpha-adrenoceptors in the human placenta are
      alpha 2. Comparative binding studies were performed, using recently synthesized
      compounds (Beecham Pharmaceuticals, UK) selective for alpha 2A (BRL-44408) and
      alpha 2B (BRL-41992) subtypes. The results indicate that human placenta contains
      at least two pharmacologically distinct alpha 2-adrenoceptor subtypes with
      approximately 60 per cent alpha 2A and 40 per cent alpha 2B receptors. In
      contrast with the pattern of increasing beta-adrenoceptor density, the
      concentration of alpha 2-adrenoceptors in term placentae is significantly lower
      than in placentae from the first trimester.

PMID- 7824453
TI  - [When should transesophageal echography be ordered?].
AB  - The exceptional quality of cardiac imaging, access to otherwise inaccessible
      anatomic areas and optimal alignment on anatomic structures make transoesophageal
      echography an exceptional high performance imaging technique. But when should it
      be ordered? Suspected aortic dissection is a major indication for
      transoesophageal echography. Diagnosis can be confirmed with sensitivity and
      specificity of 95 to 99%. The performance of the transoesophageal route is also
      better than that of the transthoracic route in case of suspected infectious
      endocarditis and should be ordered when the transthoracic image is insufficient,
      a perivalvular abscess is suspected, fever persists, infection on a prosthesis is
      suspected, blood cultures are negative or heart failure compromises cardiac
      performance. It should be remembered however, that a normal transoesophageal
      echography cannot eliminate the diagnosis of infectious endocarditis. The method
      is however extremely useful for close follow-up of endocarditis. Thrombo-embolic
      events with neurological or peripheral expression are also frequent indications
      for transoesophageal echography. Three direct causes can be detected: thrombus in
      the left atrium, contrast in the left atrium corresponding to micro-platelet
      aggregation due to prolonged stasis and intra-aortic debris. Septal anomalies may
      indicate an indirect cause. Aortic or mitral valvulopathies are another area of
      importance because transoesophageal echography results are well correlated with
      haemodynamic performance. Patients with a poorly tolerated mitral regurgitation
      with or without criteria of gravity could benefit from transoesophageal
      echography. Valve prostheses, especially mitral prosthesis, are also important
      indications. Per-operative examinations are particularly important for evaluating
      valve replacement quality after cardiac circulation has been reestablished. In
      addition, the high quality of transoesophageal images is particularly useful in
      investigating congenital cardiopathies and in certain intensive care patients.

PMID- 7824454
TI  - [Vasculitis and neurologic manifestations related to HTLV-1].
AB  - OBJECTIVES: The most common neurological picture associated with HTLV-1 infection
      is a slowly progressive spastic paraplegia often involving nerve and muscle
      inflammation. We report here six cases of inflammatory vasculitis of the nervous
      system observed among HTLV-1 infected patients. METHODS: HTLV-1 infection was
      diagnosed in 6 female patients, mean age 58 years (range 40-77 years) using
      ELISA, Western blot or polymerase chain reaction. RESULTS: All 6 patients
      presented a pyramidal syndrome which was associated with peripheral neuropathy in
      3, myositis in 1 and a sicca syndrome in 3. Two groups of patients could be
      identified. In 3 patients, the neurological picture was typical of HTLV
      infection; pathology examination of biopsy material revealed necrozing
      vasculitis. In 3 other patients, the clinical course was particularly rapid,
      highly suggestive of anterior spinal artery infarction, associated, in 2, with a
      major inflammatory syndrome. CONCLUSION: These 6 cases demonstrate that
      vasculitis can be associated with HTLV-1 infection as has been observed in HIV
      infected patients. In certain cases, clinical signs of vasculitis may be lacking
      while in others they may dominate the clinical manifestations.

PMID- 7824455
TI  - [Severe malaria in an African seasonal endemic area. Comparison of aspects in
      adults and children and prognostic value of cytokines].
AB  - OBJECTIVES: The present study was conducted in West Africa in a region where
      malaria exists as a seasonal endemic disease. The aim was to compare clinical and
      biological aspects of adult severe falciparum malaria with those found in
      children and to appreciate the role of cytokines a prognostic markers. Thirty-one
      patients fulfilling the WHO criteria of severe malaria were included. METHODS:
      Fifteen children (8 boys and 7 girls; mean age: 7.9 +/- 3.7 years) were compared
      with an adult group of 16 patients (9 men and 7 women; mean age: 31.1 +/- 14.5
      years). The number of severe criteria and most of the biological features
      (glycaemia, parasitaemia, haemoglobin levels, platelet count) were similar in
      both groups. As regards immunological findings, serum levels of IgM and IgG were
      significantly increased in the adult group. Serum levels of TNF alpha, IL-6 and
      IL-2SR were similar (255.2 +/- 375.3 versus 298.4 +/- 254.1 pg/ml for TNF alpha,
      534.6 +/- 642.7 versus 609.5 +/- 1217.0 pg/ml for IL-6, 253.1 +/- 120.5 versus
      297.6 +/- 142.2 pg/ml for IL-2SR). Each of these cytokines correlated with the
      others and were also correlated to parasitaemia. Three children and two adults
      died during the course of the study. At admission a significant died during the
      course of the study. At admission a significant difference was observed between
      serum levels of TNF alpha (p < 0.01), IL-6 (p < 0.001) and IL-2SR (p < 0.05) in
      patients who were later survivors or non-survivors. CONCLUSION: This study
      confirms the prognostic significance of serum levels of TNF alpha, IL-6 and IL
      2SR in severe malaria.

PMID- 7824456
TI  - [Post-infarction rupture of the heart into the pericardium. Surgical treatment
      combining synthetic patch and biological fibrin glue].
AB  - A 66-year old man was hospitalized with chest pain and acute ischaemia of the
      lower limbs highly suggestive of dissection of the aorta. Computed tomography and
      aortography however showed pericardic effusion and thrombosis situated in the
      iliac bifurcation of the aorta. During the emergency operation, acute tamponade
      required sub-xyphoid drainage. The haemodynamic situation was reestablished and
      the operation continued but within minutes a cataclysmal haemorrhage occurred
      through the drainage tube due to ischaemic rupture of the lateral wall of the
      heart into the pericardium. Extra-corporal circulation was installed immediately
      and a large polytetrafluoroethylene patch was sutured to the epicardium, distally
      from the necrosed area, in healthy tissue. A biological fibrin glue was injected
      under the patch. The operation was terminated with an axillo-bifemoral bypass.
      The postoperative period was satisfactory and the patient was discharged. At the
      six months examination, the patient was in NYHA class II and the echography
      showed moderate left ventricular dysfunction with grade II mitral regurgitation
      and a false aneurysm facing the area of necrosis. This technique allowed us to
      patch the rupture without excessive tension on the sutures in the fragile tissue
      which would have increased the risk of secondary rupture. In addition, the large
      patch avoided excessive reduction in volume of the left ventricular cavity and
      saved the mitral chordae which would have been destroyed by direct suture. This
      method can be an effective salvage technique for heart rupture during the acute
      phase of myocardial infarction and offers the possibility of a second look in
      case of a secondary false aneurysm.

PMID- 7824457
TI  - [Therapeutic approach in arterial hypertension with renal artery stenosis].
AB  - Screening for renal artery stenoses in hypertensive patients aims at detecting
      lesions whose treatment (renal revascularization) will normalize or reduce blood
      pressure and correct or prevent reduced glomerular filtration. Consequently,
      screening tests such as renal artery duplex Doppler scanning, renal scintigraphy
      or digital-subtraction angiography are used in patients in whom hypertension is
      severe, drug-resistant or associated with renal failure. Surgical repair or
      transluminal angioplasty is not warranted for all stenoses, however, particularly
      in atheromatous stenoses where these procedures have a 1% mortality, a 10%
      morbidity and a 30% failure rate to improve blood pressure despite adequate
      anatomical outcome. Predictors of favourable blood pressure outcome following
      revascularization are aetiological (fibrous dysplasia rather than atheroma),
      historical (young age, short duration of hypertension), physiological (renal
      ischaemia confirmed by scintigraphy, lateralizing renal vein renin ratio) and
      anatomical (truncal rather than ostial or branch stenoses). Outcome of surgery
      and transluminal angioplasty has only been documented in retrospective,
      uncontrolled reports in which blood pressure improvement is overestimated via the
      placebo effect, habituation to blood pressure readings and optimization of drug
      treatment, the latter being frequently required despite adequate
      revascularization. The first prospective randomized trials evaluating angioplasty
      in atheromatous stenoses are underway and should provide objective information
      concerning the risk/benefit ratio of this procedure.

PMID- 7824458
TI  - [New methods in lipid research].
AB  - Arteriosclerosis is an insidious multifactorial disease. Treatment relies mainly
      on prevention. Abnormal lipoproteins are major risk factors leading to
      arteriosclerosis in general and specifically to coronary artery disease. Lipid
      related risk factors should be evaluated in a stepwise process. The first step
      involves screening for raised fasting levels of blood cholesterol and
      triglycerides. Depending on the initial results, further classification may be
      required based on the blood levels of high density lipoproteins (HDL).
      Concentration of low density lipoproteins (LDL) can be calculated from blood
      cholesterol, triglycerides, and HDL levels. These two parameters, HDL-cholesterol
      and LDL-cholesterol are essential to evaluate the risk of coronary artery
      disease. Currently, it is difficult to interpret the results of apolipoprotein AI
      and B assays since it has not been proved that the evaluation of coronary risk,
      as defined from HDL-cholesterol and LDL-cholesterol levels, is modified with the
      incorporation of apolipoprotein values. In addition, assay methods have not been
      standardized, hindering the use of apolipoprotein levels in evaluating risk. The
      basic assay methods provide a wide range of results, making it possible to
      measure subfractions of lipoproteins which would play a protective preventive
      role against arteriosclerosis. Lipoprotein A1 (LpAI) is protective while Lp(a) is
      an atherogenic lipoprotein. Both LpAI and Lp(a) are now routine laboratory tests
      and provide essential information for helping the clinician define the risk of
      arteriosclerosis and thus to make therapeutic decisions. In the future, genetic
      markers will undoubtedly provide better means of appreciating the
      pathophysiological mechanisms of arteriosclerosis and thus the risk of arterial
      lesions.

PMID- 7824459
TI  - [Circulating thrombomodulin, a marker of acute systemic lupus erythematosus].

PMID- 7824461
TI  - [Simultaneous breast cancer and Hodgkin's disease. A case].

PMID- 7824460
TI  - [Late ventricular potentials and antimalarial treatment with halofantrine].

PMID- 7824462
TI  - [Hairy cell leukemia and acquired idiopathic sideroblastic anemia: an uncommon
      association].

PMID- 7824463
TI  - [Late infectious complications of celioscopic cholecystectomy].

PMID- 7824464
TI  - [Coronary disease: should images be treated?].
AB  - Precise digitized images of the coronary arteries displaying the dimensions of
      high risk stenoses and giving objective measurements of their contours and
      density can be provided by coronarography. On-line angioscopic images of tissue
      flaps floating in the lumen, recent or structured thrombi, artery wall
      dissections, plaque ruptures, deep fissurations and sub-intimal haemorrhages
      demonstrate, in live colour, the pathophysiological mechanisms of coronary artery
      stenosis. Histological sections of the artery wall, without biopsy, can be
      visualized with endocoronary echography offering a global view of the wall and
      differentiating all the physiological layers including the intima and the
      internal elastic lamina, the blood-wall interface, the media and the adventitia.
      Our technical imaging capacity is impressive, but is anatomic imaging synonymous
      with coronary circulation? Certainly not. Sophisticated imaging techniques have
      led us to associate the severity of the stenosis with its effect on myocardial
      irrigation, but today therapeutic decisions require not only considering coronary
      anatomy but also downstream consequences which can be evaluated by measuring
      coronary artery flow on both sides of the stenosis. Carried on the tip of the
      angioplasty guide, a piezo-electric crystal emits and receives a Doppler signal.
      The data is processed in real time giving a complete pattern of blood flow
      velocity and describing diastolic and systolic flow, differences between upstream
      and downstream flow, and the effect of pharmacological or physiological tests
      such as maximal dilatation to measure coronary vascular reserve. Transstenosic
      pressure measurements complete the diagnostic armentorium. Thus therapeutic
      decisions can now be made not only on the basis of precise anatomic imaging, but
      also on functional imaging, giving a complete view of the pathophysiology of the
      coronary arteries and the effect of disease on myocardial blood supply. It is now
      up to us to optimize these imaging techniques and to propose treatments which
      provide patients with coronary artery disease with the best benefit-risk-cost
      ratio.

PMID- 7824465
TI  - [Congenital toxoplasmosis, evaluation of the prevention policy].
AB  - OBJECTIVES: This study was performed to assess the effect of a prevention
      programme against congenital toxoplasmosis conducted as part of the French health
      policy developed in the Rhone department. METHODS: A descriptive epidemiological
      survey was conducted in 1991 including 806 post-partum women who were
      hospitalized in 22 maternities in the Rhone department. RESULTS: Forty-nine
      percent of the women had negative serology tests. French legislation requiring
      detecting non-immunized women at diagnosis of pregnancy was applied
      satisfactorily by the attending physicians. Inversely, women at risk were
      insufficiently informed: only 17% of the women at risk were aware of the three
      main routes of contamination; 63% believed vaccination is possible and 11% though
      they had been vaccinated. Deficient information was probably the cause of poor
      compliance to preventive measures as observed in this sample: only 17% of the
      serologically negative women stated they had applied anti-toxoplasmosis
      prophylaxy measures. CONCLUSION: Women at risk must be informed to convince them
      to modify their behaviour during pregnancy. The role of the attending physician
      and biologist is of major importance.

PMID- 7824466
TI  - Adult Burkitt's lymphoma: two patients with an unusual clinical picture.

PMID- 7824467
TI  - [Hypertrophic cardiomyopathy caused by cytochrome-oxidase deficiency].
AB  - Mitochondrial cytopathies are due to genetic anomalies in the oxidative
      phosphorylation enzymes (excepting Krebs cycle, pyruvate and certain other
      mitochondrial enzymes). Recently discovered, these diseases have a characteristic
      heterogeneous clinical expression because of the ubiquitous nature of this
      intracellular organelle. We observed a case in a 16-year-old girl who had
      cytochrome C oxidase deficiency. The child was born to non-consanguinous parents
      and had a healthy brother. The first manifestation of the disease was a systolic
      murmur heard at the age of 4 years. Progressively, exertion dyspnoea, lipothymia
      with cyanose led to the first echocardiography at 8 years revealing non
      obstructive cardiomyopathy. Functional inadaptation of cardiac performance
      worsened requiring various symptomatic treatments. At the age of 16, the
      symptomatology included lower limb fatigue and the diagnosis of a metabolic
      disease was entertained. Phosphorylase A and B activity and phosphokinase
      activity were normal. High lactic acid levels after exertion suggested a
      mitochondrial enzyme deficiency. The diagnosis of cytochrome C oxidase deficiency
      was confirmed by spectrophotometric and polarographic assay of mitochondria from
      a peripheral muscle biopsy. Treatment with riboflavin, ascorbic acid, factor P,
      menadione, carnitine and iron sulfate has currently provided some symptomatic
      improvement. In patients with unexplained cardiomyopathy, the diagnosis of
      mitochondrial cytopathy should be entertained if oxidoreduction potentials
      (lactate/pyruvate ratio) are perturbed. The diagnosis is confirmed by enzyme
      studies of fresh muscle mitochondria. Currently therapeutic prospects are at best
      very poor. Genetic counselling may be advisable.

PMID- 7824468
TI  - [Thoracoscopic approach of pericardial effusion].
AB  - We report the technique of pericardial approach through the thoracoscope. This
      approach has several advantages. Extensive pericardial fenestration can be
      performed as well as pericardoscopy whenever indicated and additional biopsies
      such as mediastinal or lung parenchyma biopsies. Among the 12 patients operated
      on, the procedure was possible in all but one case. When there is no
      contraindication to selective tracheal intubation or lateral positioning, the
      thoracoscopic approach is the method of choice. In other cases, the subxiphoid
      approach remains indicated.

PMID- 7824469
TI  - [Atypical mycobacterial infections].
AB  - Infrequent and forgotten before the advent of the acquired immune deficiency
      syndrome (AIDS), non-tuberculous mycobacterial infections are now often
      encountered, predominately in patients positive for the human immune deficiency
      virus (HIV). In non-AIDS patients, Mycobacterium kansasii, M. avium and M. xenopi
      are the most common causal agents of pulmonary mycobacterial infections. Nodes
      and skin diseases are less frequent. M. kansasii infections are treated for 12
      months with a standard combination of rifampin, isoniazid and ethambutol. The
      treatment for M. xenopi and M. avium infections have not yet been standardized.
      The AIDS epidemia has modified the epidemiology of these disease and there has
      been a 10-fold increase in incidence. Disseminated M. avium infections occur in
      15% of patients at end-stage AIDS. This new epidemia has triggered research
      leading to the discovery of new diagnostic procedure including blood culture
      media for mycobacteria, polymerase chain reaction (PCR) and new active drugs. New
      active macrolides such as clarithromycine and azithromycine are active against M.
      avium and new rifampicin-related drugs such as rifabutine and new quinolones are
      under investigation.

PMID- 7824470
TI  - [Lipoprotein (a)].
AB  - Lipoprotein(a) or Lp(a) is similar to low density lipoproteins (LDL), but also
      contains a large glycoprotein molecule called apo-lipoprotein(a) or apo(a). The
      lipid composition of Lp(a) is nearly identical to that of LDL. The structure of
      apo(a) is similar to that of plasminogen. Several genetic polymorphisms have been
      described for apo(a). The increasing interest in Lp(a) is due to the positive
      correlation which exists between the plasma level of Lp(a) and the incidence of
      ischaemic heart disease. Plasma Lp(a) level varies greatly from one individual to
      another and is basically dependent on genetic factors, especially for the
      isoforms of apo(a). A level above 30 mg.dl is associated with increased risk of
      atherosclerosis-related diseases. There are few treatments which are effective in
      significantly reducing raised levels of Lp(a).

PMID- 7824471
TI  - [Haloperidol, a new cause of rhabdomyolysis, in the absence of neuroleptic
      malignant syndrome].

PMID- 7824472
TI  - [Immuno-allergic meningeal reaction following anti-flavivirus vaccination].

PMID- 7824473
TI  - [Inappropriate secretion of antidiuretic hormone in antiphospholipid syndrome].

PMID- 7824474
TI  - [Plasmodium falciparum malaria: type R1 quinine resistance in East Africa].

PMID- 7824475
TI  - [Antiphospholipid antibodies in Basedow disease].

PMID- 7824476
TI  - [Role of the treatment of acute lymphoblastic leukemia in case of cerebral vein
      thrombosis].

PMID- 7824477
TI  - [Measuring gastroesophageal reflux in children].
AB  - The risk of gastroesophageal reflux in children has been recognized in many
      situations, particularly in ear, nose and throat affections and in chronic
      recurrent respiratory diseases. In addition, in the sudden infant death, a
      certain number of malaises may be directly related to gastroesophageal reflux via
      a vagal mechanism. Search for improved comfort for babies exposed to painful
      oessophagitis is another reason for careful evaluation, particularly since
      effective treatment is available. The evaluation of gastroesophageal reflux aims
      at identifying the underlying mechanism. Simultaneous recordings of lower
      sphincter pressures and pH variations demonstrate the essential role of
      inappropriate sphincter activity. Oesophagitis results from both prolonged
      exposure to acid and probably to pepsin, leading to local inflammation. The
      oesophagitis in turns aggravates sphincter hypotonicity. The oesophageal orifice
      of the diagphragm could also be involved. The clinical examination is essential
      to distinguish among the myriad of signs observed in infants and children with
      suspected reflux. When the symptomatology is particularly scant or when the
      general health status is unaffected further exploration may not be required. If
      however, respiratory manifestations appear to be a complication of reflux,
      complimentary tests are needed. While the diagnosis may be confirmed with pH
      metry, fibroscopy may be needed to evaluate the anatomical situation and the
      effect of the oesophagitis on the upper digestive tract. Much progress has also
      been made with endoscopic explorations which can identify cardial insufficiency
      and precisely describe the anatomy of the hiatal region. Treatment relies
      basically on prokinetic agents. The effectiveness of postural measures are
      currently questioned.

PMID- 7824478
TI  - [Erection disorders: efficacy and tolerability after 6 months of intracavernous
      self-injections of alprostadil. Groupe Francais d'Etude de l'Alprostadil].
AB  - OBJECTIVES: Self-administered intracavernous injections, notably with alprostadil
      are currently the most widely used non-psychotherapeutical treatment of erectile
      dysfunction. We assessed the effectiveness of this treatment after 6 months of
      self-injections. METHODS: Efficacy, acceptability and tolerance to alprostadil
      self-administered via intracavernous injections for 6 months was evaluated in 144
      men, age 24 to 72 years, and followed monthly after an initial training period
      and search for the optimal dose. RESULTS: The mean number of self-injections was
      5.5 at a mean dose of 18.6 micrograms per injection. From the first to sixth
      month, the frequency of complete erections after self-injection rose from 62% to
      77% and failures declined from 8% to 3%. After six months, 40% of the patients
      had abandoned the treatment including 9% who abandoned during the first month,
      usually due to poor acceptance and because of cure in two patients (4.5%).
      Patients reported sexual intercourse after self-injections as satisfactory in 81%
      of the cases; 66% of their partners reported satisfactory intercourse. Tolerance
      assessment revealed pain in 14% of the patients and decreasing effect with time
      in two patients who discontinued self-injections for this reason. Other
      undesirable side effects were infrequent, usually related to technical injection
      errors and decreasing effect with time. One case of priapism and two indurations
      of the cavernous bodies were also observed. CONCLUSION: Self-administration of
      intracavernous alprostadil can lead to rigid erection in patients with erectile
      dysfunction. Patients are generally well satisfied and tolerance is good.

PMID- 7824479
TI  - [Adamantinoma of the proximal end of the tibia. A case].
AB  - Adamantinoma is a rare primary tumour of long bones containing mesenchymatous and
      epithelial cells. There has been some controversy over the pathogenesis. We
      observed a localization in the right tibia. A 22-year-old patient from Algeria
      was seen for spontaneous progressively increasing pain in the upper part of the
      right tibia. The patient's general health had deteriorated somewhat, with fever.
      On examination there was ulceration of the skin, costal and pelvic pain and
      inflammatory right inguinal lymph nodes. Radiography revealed lateral metaphyseal
      lytic image with interruption of the cortex also seen on magnetic resonance
      imaging which revealed invasion of the soft tissue and multiple bilateral
      pulmonary nodules. Bone scintigraphy showed several zones of hyperfixation. The
      diagnosis of adamantinoma was confirmed by pathology examination of the biopsy
      specimen. On surgical exeresis, the capsule of the knee joint was found to be
      involved without invasion of the knee joint. Node dissection showed inguinal and
      popliteal invasion. Macroscopically, the surgical specimen was a red-whitish
      osteolytic tumour. Microscopically, the tumour was composed of hyperchromatic
      epithelial cells in an abondant fibrous stroma. Immunohistochemical studies were
      negative for vimentine, cytokeratin and factor VIII. Adjuvant chemotherapy was
      based on a sarcoma protocol. Unfortunately, after two cycles, white cell counts
      fell sharply and multiple skin nodules appeared together with progression of the
      bone metastases. The chemotherapy was modified without any therapeutic effect and
      the patient died in February 1993. An epithelial origin would appear most
      probable, but at least two groups of adamantinoma can be described: one with
      typical epithelial differenciation and one overlapping to the differential
      diagnosis of osteofibrous dysplasia. Although considered as a low grade malignant
      tumour, we emphasize the aggressive forms with local relapse or metastatic
      resistance to chemotherapy. Treatment relies on wide surgery and prognosis is
      generally good. Neither chemotherapy nor radiotherapy has stood the test of time
      in cases with metastasis.

PMID- 7824480
TI  - [Quantifying dyspnea].
AB  - Several methods have been proposed in the recent years to quantitate dyspnoea in
      healthy subjects or patients. Dyspnoea can be serially assessed on exercise,
      using either a visual analogue scale or a Borg scale, and is usually analyzed in
      relation to ventilation, which defines a dyspnoea threshold and a
      dyspnoea/ventilation slope. Inhaled bronchodilators, oral morphine, continuous
      (or inspiratory) positive airway pressure or respiratory rehabilitation
      programmes are able to decrease the dyspnoea/ventilation slope in patients with
      chronic obstructive pulmonary disease, while atenolol and pneumectomy have a
      deleterious effect. Measurement of dyspnoea in everyday life is feasible using
      the oxygen cost diagram or the baseline dyspnoea index; these indices are
      responsive to therapy, e.g. to oral theophylline in patients with chronic
      obstructive pulmonary disease. Dyspnoea measured at rest is a marker for
      evaluating the perception of added loads (open scale) or acute
      bronchoconstriction in normals or patients; in the latter it may also reflect the
      perception of the degree in baseline ventilatory impairment or that of acute
      bronchodilation (bipolar visual analogue scale). Some respiratory patients being
      poor perceivers, methods able to improve the perception of airway obstruction are
      desirable in these individuals.

PMID- 7824481
TI  - 100 years on: tissue coagulants and anticoagulants. A role in arteriosclerosis?

PMID- 7824482
TI  - [Disseminated Propionibacterium acnes cutaneous infection in a neutropenic
      patient].

PMID- 7824483
TI  - [Gastric metastasis complicating the course of lobular adenocarcinoma of the
      breast in a male patient].

PMID- 7824484
TI  - [Hypereosinophilia and cutaneous lesions caused by low-molecular-weight heparin].

PMID- 7824485
TI  - [Preoperative embolization of uterine fibroma. Preliminary results (10 cases)].

PMID- 7824486
TI  - [Post-cesarean section gas gangrene. A case].

PMID- 7824487
TI  - [Primary lymphoma of the adrenal glands].

PMID- 7824488
TI  - [Retinotherapy of skin diseases].
AB  - The discovery of retinoid receptors has contributed greatly to our understanding
      of the mechanism of action of vitamin A. The organism produces at least two
      ligands from ingested vitamin A which act as hormones modulating the activity of
      numerous genes via their nuclear receptor. These ligands are produced locally by
      target cells from retinol and retinaldehyde. These advances do not respond to the
      clinicians' interrogation as to why 13cis retinoic acid blocks sebaceous
      secretion and cures severe acne while other known retinoids are uneffective.
      Current research would suggest that the expression of nuclear receptors is not
      altered in skin diseases but that upstream anomalies in the intracrine system
      (enzymes and binding proteins) could be involved. Clinically, teratogenic risks
      are a major obstacle to the oral administration of retinoids and the future in
      skin diseases lies most likely in topical applications.

PMID- 7824489
TI  - [Continuous administration of vancomycin in patients with severe burns].
AB  - OBJECTIVES: In the severely burned patient, a marked, rapid fall in serum
      concentrations is often observed after intermittent infusion of vancomycin at the
      usual dose of 30 mg/kg. This specific "jagged" pharmokinetic course with
      inadequate residual concentrations raises the problem of the efficacy of this
      time-dependent antibiotic. Studies in patients in general resuscitation units
      have shown the interest of vancomycin administration in continuous infusion.
      METHODS: We analyzed variations in serum concentrations of vancomycin during
      continuous infusion in 18 patients with burns involving a mean of 40% total body
      surface and reported the doses necessary to maintain serum vancomycin at
      therapeutic levels; the possible correlations between serum vancomycin
      concentrations, burn parameters, age and renal function; and clinical and
      biological tolerance. RESULTS: Higher initial doses were required in burn
      patients (40 mg/kg in patients aged under 60) than in other patients. Impairment
      of renal function is a contra-indication of continuous infusion. CONCLUSION: This
      mode of administration has the advantage of ensuring greater efficacy by
      preventing fluctuations in serum concentrations.

PMID- 7824490
TI  - [Quantification of passive smoking in an survey of smoking coaches in the French
      high-speed trains (TGV Sud-Est)].
AB  - OBJECTIVES: Passive smoking has been demonstrated in many situations. We designed
      an experimental protocol to measure passive smoking in the coaches of the French
      high-speed train (TGV) and to attempt to identify interindividual variability in
      sensitivity. METHODS: Ten healthy non-smokers (5 males, 5 females) volunteered to
      avoid exposure to tobacco smoke for the duration of the study. On three separate
      occasion they were subjected to a 5-hour trip in the smoking coaches of the
      French TGV (south-east line). Twelve-hour urine samples were collected before
      each trip and over the following 72 hours. Urinary cotinine was measured in each
      fraction. RESULTS: Significant levels of urinary cotinine were found for a
      prolonged period in these passive smokers. Elimination of the tobacco by-product
      was similar to the level observed in subjects smoking 2 to 5 cigarettes per day.
      The kinetics of cotinine elimination was reproducible from one trip to another
      for any given individual, however significant interindividual variability was
      observed despite normal liver function in all. CONCLUSION: Measurement of urinary
      cotinine is potentially useful in non-smokers who are involuntarily exposed to
      tobacco smoke and who wish to know the extent of their exposure.

PMID- 7824491
TI  - [Congenital dilatation of the common bile duct in children. Study of a series of
      52 cases].
AB  - OBJECTIVE: The aim of this study was to evaluate results at long-term follow-up
      of patients suffering from congenital dilatation of the bile duct according to
      the type of operative procedure. METHOD: A retrospective study of 52 patients who
      were operated on during a 25-year period was carried out. Of 52 patients, 43
      (83%) were female and 9 (17%) were male, with a ratio of 4.8/1. In six cases, the
      diagnosis was made antenatally by ultrasonography. Transhepatic cholangiography
      showed an extrahepatic dilatation in 25 cases (48%) and a combined extra and
      intrahepatic dilatation in 27 cases (52%). A common bilio-pancreatic channel was
      found in 25 patients. Mean age at the time of operation was 4.2 years. Operative
      procedures included: cyst excision and hepaticojejunostomy in 47 cases,
      cystojejunostomy or cystoduodenostomy in 4 cases and cystostomy in one case.
      There were two postoperative deaths. RESULTS: Long-term follow-up was established
      in 43 of 50 survivors (80%). One patient was reoperated because of portal
      hypertension. Cholangitis developed in 11 patients: 2/2 patients who had
      undergone in internal drainage and 9/41 patients who had undergone a cyst
      excision with hepaticojejunostomy. In patients with cyst excision, cholangitis
      developed twice as frequently in those with associated intrahepatic dilatation.
      Two of 11 children with recurrent cholangitis died following sepsis, and three
      others were reoperated because of intrahepatic bile duct stones, one of these 15
      years later. CONCLUSION: A total excision of the extrahepatic biliary tract,
      followed by hepaticojejunostomy is considered as a treatment of choice. The site
      of the biliary anastomosis should be adapted to the type of dilatation of
      intrahepatic bile duct in the case of a combined extra and intrahepatic
      dilatation.

PMID- 7824492
TI  - [Exercise training and rehabilitation techniques in patients with coronary
      disease].
AB  - Exercise rehabilitation is widely prescribed for patients with coronary artery
      disease and requires the same rigorous approach as physical training in athletes.
      Training techniques have been carefully described, but the precise physiological
      justification remains to be elucidated. In order to target the physiological
      mechanisms which rehabilitation training is designed to improve, it is necessary
      to have a coherent strategy and apply the techniques with a clear idea of the
      objective to be attained. We describe the programme we propose to our patients.
      First, patients are advised to fraction their exercise into short relatively
      intense periods of exertion separated by rest periods as long as the exertion
      period. This method is designed to develop the "power" of the aerobic energy
      system. Later, we progressively introduce longer periods of training at moderate
      intensity. This part of the rehabilitation is designed to develop the "capacity"
      of the aerobic system. The decision to develop work capacity is based on the
      patient's response to the first part of the rehabilitation programme.

PMID- 7824493
TI  - [Virological diagnosis and treatment of respiratory syncytial virus infections].
AB  - Respiratory syncytial virus infections occur frequently in children, often
      localized in the upper respiratory tract. Outcome is usually quite satisfactory,
      but in nearly one half of the infants lower tract involvement may cause severe
      respiratory insufficiency leading to hospitalization in about 1% of the cases.
      Its frequency has been estimated at 20 to 30% of the viral infections in
      hospitalized infants, 10 times the frequency of the other respiratory virus.
      Respiratory syncytial epidemias last about 4 to 5 months with a seasonal peak in
      december and january. The direct detection of respiratory syncytial antigens in
      nasal specimens by immunofluorescence or enzymatic immunoassay is the key to
      rapid diagnosis. They appear as performant and more convenient than specific IgM
      antibodies or nucleic acid detections, and than virus isolation on cell culture,
      which is justified to evaluate strain sensitivity to ribavirin.
      Immunofluorescence has also been used to identify the subgroups A and B from 1981
      to 1993, and respiratory syncytial subgroup A seems to signify more severe
      disease. Symptomatic assistance may require hydratation, oxygenotherapy and
      respiratory physical therapy. Antibiotics should not be given as a routine
      treatment since bacterial superinfection is infrequent, but may be indicated in
      cases with associated signs of complications. Indications for bronchodilators and
      corticosteroids are still under debate. Significant results have been obtained
      with ribavirin and specific anti respiratory syncytial immunoglobulins but
      further evaluations are still required to precise their use in clinical practice.

PMID- 7824494
TI  - [Multiple sclerosis: role of growth factors and remyelination].
AB  - Multiple sclerosis is a frequent and often disabling neurological disease. Its
      aetiology and treatment remain to be discovered. It has been demonstrated in
      multiple sclerosis brains that remyelination can occur after the myelin damage.
      This myelin repair is achieved by oligodendrocytes, which are the myelinating
      cells of the central nervous system or by oligodendrocytes precursors still
      present in adult central nervous system. Several recently discovered growth
      factors can stimulate oligodendrocytes precursors migration and proliferation, or
      act as survival factors for mature oligodendrocytes. These glial growth factors
      may represent a new therapeutic approach in multiple sclerosis, aiming at the
      stimulation of the endogenous capacities of remyelination.

PMID- 7824495
TI  - [Hemophagocytosis syndrome in Mediterranean boutonneuse fever].

PMID- 7824496
TI  - [Acute alithiasic cholecystitis caused by interleukin-2].

PMID- 7824497
TI  - [Early reappearance of varicella-zona virus in the cerebrospinal fluid after
      treatment with foscarnet in AIDS].

PMID- 7824498
TI  - [Pseudo-asthma].

PMID- 7824499
TI  - [Roentgen findings in bronchial tuberculosis].
AB  - To determine the value of chest roentgenographic findings in the diagnosis and
      therapy of endobronchial tuberculosis we analysed roentgenograms of 41 patients
      with endoscopically confirmed tuberculous involvement of the intrathoracic
      airways. 40 patients had infiltrates typical for pulmonary tuberculosis
      predominantly in the upper lobes. Signs of diminished air entry in form of
      collapse or consolidations were found in 52%. 10 patients had cavities and two
      had a destroyed lung. In only one patient the chest roentgenogram was completely
      normal demonstrating a case of isolated endobronchial tuberculosis. During
      antituberculosis drug therapy radiological signs improved in 38 of 41 patients,
      but in more than half of the cases stenoses persisted as verified by
      bronchoscopy. We conclude that endobronchial tuberculosis is usually accompanied
      by lung parenchyma involvement and that roentgenological findings are
      characterised by signs of pulmonary tuberculosis in most cases. A normal chest
      roentgenogram does not exclude endobronchial tuberculosis. Despite
      roentgenographic improvement during therapy tracheobronchial stenoses may
      persist. These findings justify to perform early fibreoptic bronchoscopy. Sputum
      conversion during the clinical course may indicate the most appropriate time for
      this examination.

PMID- 7824500
TI  - [Diagnosis of adrenal cortex insufficiency in steroid-dependent bronchial asthma-
      the CRH test in comparison with diurnal cortisol profile in serum and cortisol in
      24-hour urine].
AB  - In 50 patients with bronchial asthma requiring systemic treatment with
      glucocorticoid preparations, a CRH test has been performed in addition to the
      conventional determination of cortisol in the serum and 24-h urine in order to
      evaluate the function of the hypothalamo-pituitary-cortico-adrenal axis.
      According to the CRH test, 19 of the 50 patients were suffering from
      corticoadrenal insufficiency, whereas both the conventional tests had yielded a
      high percentage of false-positive and false-negative findings. There was no
      indication for the assumption that development of insufficiency of the
      corticotropic axis was in any way dependent on the glucocorticoid preparation or
      on the dosage or duration of treatment.

PMID- 7824501
TI  - [New approaches to evaluation of nonspecific inhalation provocation (dose
      response relationship) in the comparative evaluation of bronchial hyperreactivity
      within the scope of clinical trials].
AB  - For the performance of clinical drug trials in the therapy for bronchial
      hyperresponsiveness, unspecific inhalatory provocation tests are generally
      employed to judge therapeutic success. In particular, the parameter-specific
      provocation doses are considered to be the main target values. However, it must
      be considered that these provocation doses are not equally calculable for every
      patient in the same way and at any examination time. This leads to the fact that
      the number of evaluable case studies is often appreciably lower than the number
      of test participants and that a meaningful therapy group comparison may even not
      be possible under certain circumstances. An evaluation model is presented here in
      order to fully exploit the obtained data; in this the percentile changes of the
      function parameters (estimated by linear regression) at a defined dose of the
      provocation substance are analyzed. In analogy, a survival time model and, as a
      supplement, a best case/worst case analysis are performed for further statistical
      evaluation. With the present procedure, an evaluation with inclusion of all test
      participants is possible. In contrast to the previously used evaluation
      procedures, this allows a reliable statistical confirmation of the results of
      clinical tests in the therapy for bronchial hyperresponsiveness.

PMID- 7824502
TI  - [Have the incidence and resistance of tuberculosis increased? Epidemiologic
      follow-up based on diseases confirmed by culture].
AB  - The unexpected increase in the incidence of tuberculosis in many industrialized
      countries, which was recorded in Germany for the first time in 1992, provided the
      incentive for this retrospective analysis over the past 13 years of the
      epidemiology and resistance situation for Tbc in the Rhine/Main area. Basis for
      the evaluation were the data from our laboratory which is the only institution in
      the region performing type and resistance determinations on mycobacteria. During
      the period of the investigation, in which 3,738 tuberculoses were confirmed in
      cultures, the number of cases of the disease among German citizens decreased
      continuously. However, the still stagnating incidence rates can probably be
      attributed to the increasing flow of immigrants from countries with a high Tbc
      prevalence. Extrapulmonary manifestations were detected more often among
      foreigners than among Germans (19.6% versus 13.3%, p < 0.0001). In 9.5% of the
      cases, resistance against at least one of the five primordial antituberculosis
      agents (INH, SM, EMB, RMP, and PZA) was observed; but the rate was almost twice
      as high among foreigners as among Germans (13.8% versus 7.4%, p < 0.001). An
      increase in resistance either against individual substances or in regard to
      combination resistance could not be observed. In spite of the relatively high
      number of HIV-positive persons in the Frankfurt region, HIV-associated
      tuberculosis is still too seldom to make a noticeable impression on the total
      incidence. In the light of the regional incidence and resistance rates determined
      by us, a special position or even pace-setting function of our conurbation within
      the epidemiological tuberculosis situation in Germany cannot be recognized at
      present.

PMID- 7824503
TI  - [An unusual form of silicosis caused by exposure to a priming putty (Asplit ET)].
AB  - A case report on a 59-year-old male patient is given who had been exposed for 30
      years to silica flour when mixing the primer Asplit ET. To some extent the
      diagnostic findings were uncommon for silicosis and rather suggested the
      diagnosis of a usual interstitial pneumonitis. Only transbronchial lung biopsy
      and histologic examination inclusive energy-dispersing x-ray microanalysis was
      able to prove a complicated form of silicosis.

PMID- 7824504
TI  - HPV detection using "hot start" polymerase chain reaction in patients with oral
      cancer: a clinicopathological study of 64 patients.
AB  - We examined the incidence of human papillomavirus (HPV) in intraoral cancers from
      64 patients as determined by the highly sensitive technique of "hot start"
      polymerase chain reaction (PCR) in formalin-fixed paraffin-embedded tissues.
      Polymerase-chain-reaction-amplified HPV DNA was detected in the carcinomas of 16
      patients (25%). The percentage of men in the HPV-positive (HPV+) group was
      greater than that in the HPV-negative (HPV-) group (86% versus 68%), but the
      difference was not statistically significant. There was no intraoral site
      preference for the HPV+ tumors. The mean age of viral-positive and -negative
      groups was similar (55 versus 53.8 yr). Three of 16 HPV+ patients (19%) had never
      smoked cigarettes; however, 16% of the HPV- group had also never smoked. Of
      interest, 38% of patients interviewed had occupation-related exposures that may
      have contributed to their carcinogenesis, and a disproportionate percentage of
      these patients (57%) were from the HPV+ group. There were no statistically
      significant differences between HPV+ and HPV- cases regarding T stage, clinical
      stage, and tumor differentiation. The disease-free interval did not differ
      significantly for HPV+ and HPV- patients in total nor when patients were
      stratified for tumor stage and clinical stage. The only group that showed some
      difference in outcome was that of the stage III/IV patients with oral cancer. We
      observed a shorter survival time for the HPV+ patients as compared with the HPV-
      patients (P = 0.09). We conclude that, in general, HPV is associated with a
      minority of intraoral cancers and its presence is not predictive of patient
      outcome.

PMID- 7824505
TI  - The synovial structure of breast-implant-associated bursae.
AB  - Over 2 million silicone breast prostheses have been implanted since they were
      introduced in the 1960s. After implantation, a fibrovascular tissue reaction
      referred to as a "capsule" is observed. Many consider this capsule to be a static
      structure, an effective barrier to the egress of foreign material. However,
      reports documenting the presence of silicone within lymph nodes of patients with
      apparently unruptured implants indicate that silicone may be transported away
      from the breast-implant capsule. To characterize the cells making up the breast
      implant capsule, 183 capsules from 103 ruptured or bleeding implants and 80
      intact implants were studied. Gross and light microscopic studies were performed
      on all, and selected capsules were subjected to ultrastructural study and Fourier
      transform infrared spectroscopy. Light microscopic examination of the capsule
      revealed an organized, layered structure with an associated network of endothelia
      lined spaces. The capsules varied in cellularity, depending on the type and
      integrity of the implant. The superficial cell layer of all capsules had
      cytoplasmic processes directed toward the surface. These long cytoplasmic
      processes contained vacuoles ultrastructurally, indicating phagocytic and
      pinocytotic capability. These cells bore immunological markers of bone marrow
      derived macrophage-type cells. The extracellular matrix of the surface layer
      consisted of an amorphous fibrillar protein lacking the ultrastructural
      periodicity of mature collagen. No cell-to-cell junctions were observed. Deeper
      capsular layers were characterized by fibroblast-type cells in a collagen matrix.
      No capsules studied contained basement membrane or basal lamina between the
      stroma of the capsule and the surface cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7824506
TI  - A comparison of commercially available probes for in situ hybridization to human
      papillomavirus DNA.
AB  - Several commercially prepared DNA probes to human papillomavirus are available
      for nonisotopic in situ hybridization. Our laboratory conducted a comparison of
      eight commercially available DNA probes for diagnostic purposes. Six type
      specific and two wide-spectrum probes from two vendors (Enzo and Digene
      Diagnostics) were used on routinely processed, formalin-fixed, paraffin-embedded
      tissue sections. An additional wide-spectrum probe from Dako was also
      investigated, but testing was discontinued early because performance was
      unsatisfactory. An automated apparatus was used for this comparison study, and
      the protocols for the kits were adapted accordingly. Twenty-four cases were
      studied; these included four cases of normal cervical tissue, six cases of
      condyloma, six cases of mild (low-grade) dysplasia with condyloma, five cases of
      moderate to severe (high-grade) dysplasia, and three cases of carcinoma. All of
      the low-grade dysplasias and the condyloma hybridized with at least one wide
      spectrum and one type-specific probe. By contrast, only half of the high-grade
      dysplasias and carcinomas hybridized to any probe. The results of hybridizing
      with the type-specific probes were equivocal. Four cases reacted with two
      different type-specific probes. We conclude that nonisotopic in situ
      hybridization is a reproducible technique for detection of human papillomavirus,
      and recommend this method as an adjunct for routine histology in equivocal cases
      of condyloma. The technique adapts to a mechanized system, increasing its utility
      in the clinical setting. In our laboratory, the Enzo wide-spectrum probe was
      easier to interpret, generating a stronger signal with less nonspecific binding
      of chromogen. The sensitivities of the probes tested were not significantly
      different.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7824507
TI  - Transforming growth factor alpha, epidermal growth factor, and epidermal growth
      factor receptor expression in normal and diseased human adrenal cortex by
      immunohistochemistry and in situ hybridization.
AB  - Because epidermal growth factor (EGF), transforming growth factor-alpha (TGF
      alpha), and epidermal growth factor receptor (EGFR) have been implicated in the
      regulation of adrenocortical function, we used immunohistochemistry and in situ
      hybridization of EGF and TGF-alpha to study 41 specimens of human adrenal cortex,
      including 10 normal specimens, 15 aldosteronomas, five Cushing's adenomas, six
      adrenocortical incidentalomas, and five carcinomas to determine what role these
      growth factors play in controlling human adrenocortical function. Neither
      immunoreactivity nor mRNA hybridization signals to EGF was detected in any
      specimens, and EGF therefore may exert its effects on adrenal function as an
      endocrine hormone. TGF-alpha expression was detected at both protein and mRNA
      levels in normal and neoplastic adrenal cortex, demonstrating that TGF-alpha is
      synthesized locally in human adrenal cortex. TGF-alpha expression was observed in
      the cells with increased steroidogenesis, including compact tumor cells and zona
      fasciculata cells with lipid depletion, but did not necessarily correlate with
      production sites of any specific steroid hormone. EGFR immunoreactivity was more
      widely distributed than TGF-alpha immunoreactivity. Both TGF-alpha and EGFR
      expression were markedly elevated in adrenocortical carcinomas. TGF-alpha and
      EGFR thus appear to be involved in biological function in both normal and
      neoplastic human adrenal cortex. In addition, TGF-alpha and EGFR may play
      important roles in some biological features of adrenocortical malignancy.

PMID- 7824508
TI  - Immunohistochemical analysis of cathepsin D in prostate carcinoma.
AB  - Cathepsin D is a carboxyl protease that has been implicated as an important
      factor in tumor cell invasion. Sixty-nine cases of primary adenocarcinoma of the
      prostate were studied by the indirect immunoperoxidase method using a primary
      monoclonal anti-cathepsin D antibody. Immunoreactivity was graded from 0
      (negative) to 4+ (intense reaction). The normal tubuloalveolar glands were, in
      general, negative. However, nine cases revealed focal staining of nonneoplastic
      luminal cells. Basal cells were negative except in areas of basal-cell
      hyperplasia, which were intensely positive. Thirty-nine of 78 carcinoma samples
      revealed 2+ or greater positive punctate lysosomal staining. In the 39 positive
      stained cases, the reactivity was diffuse in three and focal in the remainder.
      The percentage of carcinoma cases whose worst lesions stained 2+ or greater
      showed a nonsignificant (P = 0.055) relation to Gleason grade but a significant
      (P = 0.031) relationship to pathologic stage. Thus, cathepsin D may prove to be a
      useful marker of prostate cancer progression.

PMID- 7824509
TI  - Expression of neural cell-adhesion molecule isoforms and epithelial cadherin
      adhesion molecules in 47 human meningiomas: correlation with clinical and
      morphological data.
AB  - Meningiomas are derived from arachnoidal cells exhibiting both epithelial and
      mesenchymal properties. The expression of epithelial cadherin and neural cell
      adhesion molecule isoforms was examined in 47 meningioma specimens and normal
      arachnoid villi by using immunohistochemistry and immunoblot procedures. For
      immunohistochemistry, the percentage of immunostained surface versus
      counterstained surface and the intensity of labeling were quantified by image
      analysis and correlated with clinical and morphological data. Neural cell
      adhesion molecule, 140-kDa, was expressed by all meningiomas examined and by cap
      cells and the fibrous capsule forming the arachnoid villi. Neural cell-adhesion
      molecule immunostaining was correlated to tumor location, histological type, and
      grade. The expression of polysialylated isoforms was related to tumor location
      and grade, with a higher expression on convexity meningiomas and high-grade
      tumors. Epithelial cadherin was expressed with various intensity. In arachnoid
      villi, its expression was restricted to cap cells, but it was found in all
      meningiomas, whatever their histological type or grade. However, the expression
      was stronger in whorls and meningiotheliomatous areas versus fibroblastic areas.
      No correlation was observed with the tumor location or the grade. These data
      suggest that neural cell-adhesion molecule and epithelial cadherin play a role in
      the morphogenesis and histogenesis of human meningiomas.

PMID- 7824510
TI  - Evaluation of frozen sections in grossly benign breast biopsies.
AB  - Breast biopsies have traditionally been one of the most common specimens
      submitted for frozen section. However, many breast biopsies now consist of
      fibrofatty tissue with no areas grossly suspicious for malignancy. Because some
      physicians have criticized the routine use of frozen sections in such specimens,
      the usefulness of frozen sections performed on grossly benign breast biopsies was
      evaluated. Four hundred thirty-two consecutive breast biopsies having frozen
      sections were studied. Of these, 167 (38.7%) showed a mass by gross examination.
      The remaining 265 contained no areas grossly suspicious for neoplasia. Frozen
      section diagnosis was deferred in seven of these cases, with the other 258
      reported as benign. Ten of these 258 (3.9%) had small areas of in situ or
      invasive carcinoma diagnosed on permanent sections; seven of these lesions were
      not present on the frozen section slide. Twelve (4.7%) had areas of atypical
      hyperplasia (10 ductal, two lobular) identified only on permanent sections. This
      study indicates that frozen sections done on breast biopsies that are grossly
      benign do not add to the gross impression, and may be misleading mostly because
      of the false-negative rate.

PMID- 7824511
TI  - p53 mutations and MDM-2 amplification in renal cell cancers.
AB  - Genomic DNA from 53 primary human renal cell tumors was screened for the presence
      of mutations in the tumor suppressor gene p53, using the polymerase chain
      reaction and single-strand conformation polymorphism analysis, followed by direct
      sequencing of DNA. Five cases showed mobility shifts. Sequencing of these samples
      revealed two cases of nonsense mutations (codons 182, 192), one case of a
      missense mutation (codon 285), and two cases of silent mutations at codon 213.
      The frequency of mutations altering the p53 (3/53 = 6%) was low when compared
      with the reported frequencies (15% to 65%) of allelic loss of 17p (location of
      p53) in renal cell cancers, suggesting the possible existence of another tumor
      suppressor gene in the region of the p53 gene, which when mutated is associated
      with these cancers. All three tumors with p53 mutations were cases with poor
      prognosis, i.e., highest pathological grade and/or advanced Robson stage. The
      human equivalent of the murine double-minute-2 was not amplified in the renal
      cell tumors. In summary, alterations of p53 may be associated with the
      development of renal cell carcinoma of higher grade and/or stage.

PMID- 7824512
TI  - Skin involvement in myelogenous leukemia: morphologic and immunophenotypic
      heterogeneity of skin infiltrates.
AB  - A systematic morphological analysis of cutaneous infiltrates in acute myelogenous
      leukemia and myelodysplastic syndrome revealed that in many cases the
      infiltrating cells have a different phenotype from those in the bone marrow. This
      study sought to answer two questions: (a) How wide is the range of cytological
      features and immunoreactivity of the cutaneous infiltrates and what danger is
      there of misinterpretation? (b) What are the possible causes of the wide spectrum
      of differentiation of the cells infiltrating the skin? Skin biopsy specimens from
      16 patients with myelogenous leukemia or myelodysplastic syndrome were
      investigated. The diagnosis was acute myelomonocytic leukemia (M4, according to
      the French-American-British/FAB system of classification of acute leukemias) in
      eight cases, acute monocytic leukemia (M5) in four cases, aleukemic leukemia
      cutis as a recurrence of M2 leukemia after treatment in one case, and
      myelodysplastic syndrome in three cases, including one case of myelodysplasia
      with an excess of bone marrow blasts (RAEB-T) and two cases of chronic
      myelomonocytic leukemia, one of which presented as aleukemic leukemia cutis.
      Reactivity with the macrophage-associated antibodies anti-CD68, Ki-M1p, and anti
      lysozyme was the most consistent. However, the naphthol AS-D chloroacetate
      esterase reaction and staining with DAKO-M1, Ki-My2p, anti-neutrophil elastase,
      and anti-CD34 were found to be of little value for identifying the cutaneous
      infiltrate as myelogenous. Some antibodies (e.g., anti-S100 protein and MB2) even
      produced staining in a few cases that could have led to a mistaken diagnosis of
      histiocytic neoplasm or malignant lymphoma.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7824513
TI  - Proliferating-cell nuclear antigen immunocytochemistry in the evaluation of
      gastrointestinal smooth-muscle tumors.
AB  - Current methods do not provide a way always to distinguish benign from malignant
      gastrointestinal smooth-muscle tumors. We compared immunocytochemical assessment
      of proliferating-cell nuclear antigen expression with flow cytometry and mitotic
      figure-counting as a prognostic marker in 85 gastrointestinal smooth-muscle
      tumors. Although proliferating-cell nuclear antigen expression was associated
      with poor prognosis in univariate statistical analysis, it was not significant in
      multivariate proportional hazards models that included either the mitotic index
      or aneuploidy of the flow-cytometric G2M peak. We conclude that proliferating
      cell nuclear antigen assessment is not warranted in the routine evaluation of
      gastrointestinal smooth-muscle tumors.

PMID- 7824514
TI  - Oncogene amplification screening by labeled primer multiplex polymerase chain
      reaction.
AB  - This paper describes an improved procedure for rapid detection of amplified genes
      in fresh or formalin-fixed, paraffin-embedded tissues. Utilizing a multiplex
      differential polymerase chain reaction with radioactively labeled primers and
      electrophoresis of the products through thin gels, it is possible to screen for
      oncogene amplification more rapidly and reproducibly than has been previously
      demonstrated. This procedure takes advantage of thin vertical gels with external
      cooling, which allows sharp band resolution. Four separate gels can be
      electrophoresed at the same time in a single gel box. Because each gel slab
      contains 10 or more lanes, 40 or more samples can be assayed for gene
      amplification simultaneously. The entire procedure can be carried out from
      formalin-fixed, paraffin-embedded tissue to finish in 8 h when combined with a
      sonication technique for DNA extraction.

PMID- 7824515
TI  - The preparation of native livers for morphological studies.
AB  - We describe experiences with a perfusion fixation apparatus that was used for
      studies on approximately 500 native livers. Immediately after excision of the
      specimen, small samples from needle biopsy specimens are obtained for snap
      freezing and the remaining portions of the specimens are fixed and embedded in
      paraffin. In the laboratory, the portal vein and, if possible, the hepatic artery
      or common hepatic duct are then cannulated and the livers are perfused for 3 days
      with Kaiserling's solution. An electric pump drives the perfusion apparatus and
      allows the formalin to cascade through stacked plastic containers, with the
      specimens attached to the inflow nozzles for the fixative. Eight or more livers
      (or other organs and specimens) can be accommodated simultaneously. Angiograms or
      cholangiograms can be prepared before or after fixation; we prefer the latter.
      The livers are then sliced with an extra-long knife, which minimizes cutting
      marks. Most preparations are thoroughly fixed and yield excellent specimens, not
      only for routine microscopic study but also for special methods such as scanning
      electron microscopy and trace metal analysis. The liver slices can be stored
      indefinitely, which allows long-range collection for routine review or research
      purposes. In approximately 5% of the cases, specimens cannot be perfused properly
      and thus are unsuitable for this type of preparation. With autopsy specimens this
      percentage is higher, probably because of postmortem clotting. Gravity perfusion
      of the livers before placement into the apparatus generally enables
      identification of specimens with incomplete filling of the vasculature.

PMID- 7824516
TI  - Use of proliferative markers Ki-67 (MIB-1) and proliferating cell nuclear antigen
      (PC10) in transitional cell carcinoma of the renal pelvis.
AB  - Segmental renal resection and improved endourological techniques have resulted in
      conservative treatment options for transitional cell carcinoma of the renal
      pelvis. These techniques have increased the need for more objective measures of
      biological behavior. We applied two immunohistochemical markers of cellular
      proliferation, proliferating cell nuclear antigen (PCNA; PC10) and Ki-67 (MIB-1),
      to 58 archival cases of renal pelvic transitional cell carcinomas and correlated
      the percentage of positive cells to grade, stage, and survival, and to one
      another; mitotic counts (mitoses/10 high-power fields) were also performed.
      Expression of PCNA showed a significant difference between grades 1, 2, and 3
      tumors (P = 0.05) and between superficial (Ta, T1) and invasive tumors (T2-4) (P
      = 0.02). There was a significant overlap, however, in the percentage of cells
      staining between the grades as well as the stages. PCNA staining did not
      correlate with survival and did not identify a subset of patients with low-stage,
      low-grade tumors with a poorer prognosis. The Ki-67 score exhibited a stronger
      correlation with grade (P = 0.001), and there was a trend of increasing Ki-67
      expression with higher stage tumors, but this did not reach statistical
      significance (P = 0.10). Ki-67 showed comparable findings to PCNA with regard to
      survival and overlap in staining between the grades and stages. Mitotic counts
      did correlate with grade (P = 0.003) but not stage or survival. This study
      demonstrates that cellular proliferation, as determined by the
      immunohistochemical markers, Ki-67 and PCNA, is related to grade and, to a lesser
      extent, stage, but the use of these markers as measures of biological behavior in
      clinical practice may be limited.

PMID- 7824517
TI  - Telepathology is available for transplantation-pathology: experience in Japan
      using an integrated, low-cost, and high-quality system.
AB  - We examined the validity and accuracy of telepathology service in the
      histological diagnosis of biopsy specimens from human transplanted kidney and
      liver. The still video images of paraffin sections were transmitted via a two-way
      telephone by use of a digitized telephone network (Integrated Service Digital
      Networks, 64 kbits/sec). The images were displayed on monitors and diagnosed by
      an expert pathologist at Tottori University. The quality of transmitted still
      images was sufficient for the diagnosis, especially at higher magnifications. The
      average number of transmitted images was 6.2 in the kidney cases and 7.4 in the
      liver cases. The average time taken for examination of a case was 13 min (range
      10 to 16 min). Of 12 biopsy specimens from transplanted kidneys, 10 were
      adequately diagnosed with the system. Sampling errors caused inadequate diagnosis
      in a case of cyclosporin tubulopathy, the still images of which were not
      transmitted. An expert pathologist rendered the diagnosis in a case showing
      mesangial sclerosis, which was later diagnosed as possible recurrent
      glomerulonephritis through direct microscopy. Biopsy specimens from 10 liver
      transplants were also tested using archival materials. Although the etiology of
      hepatitis could not be determined in one case, diagnoses by telepathology well
      agreed with the reported diagnoses made through direct microscopy. Telepathology
      may be an effective way to provide on-line consultations in transplantation
      pathology, especially for transplant teams lacking expert pathologists.

PMID- 7824518
TI  - Eosinophilia-myalgia syndrome: a recent syndrome serving as an alert to new
      diseases ahead.
AB  - A recently recognized disease, the eosinophilia-myalgia syndrome, is described
      and presented as a new condition attributable to nutritional toxicology. Its
      etiology is related to the ingestion of L-tryptophan, manufactured by a single
      Japanese supplier who had modified its production system, which, though of high
      purity, contained in minute concentrations a number of contaminants or
      impurities. Patients with eosinophilia-myalgia syndrome develop an eosinophilia
      with pathologic changes mainly involving skin, muscle, and connective tissue. The
      findings suggest an autoimmune response. Experimental studies with the implicated
      L-tryptophan as well as with some contaminants have as yet failed to develop a
      suitable animal model of eosinophilia-myalgia syndrome. Further studies are
      needed to unravel the pathogenesis of this complex syndrome. At present,
      physicians need to be cognizant of this recent syndrome and be aware that other
      new diseases, induced by nutritional toxicological alterations and possibly
      related to technicological developments, lie ahead.

PMID- 7824519
TI  - A prediction of the secondary structure of the pleckstrin homology domain.
AB  - A consensus prediction for the secondary structure of the pleckstrin homology
      (PH) domain is presented. The prediction is based on an analysis of patterns of
      conservation and variation of homologous protein sequences. The structure is
      predicted to be formed largely from beta strands with a single alpha helix.

PMID- 7824520
TI  - Free energy simulations: the meaning of the individual contributions from a
      component analysis.
AB  - A theoretical analysis is made of the decomposition into contributions from
      individual interactions of the free energy calculated by thermodynamic
      integration. It is demonstrated that such a decomposition, often referred to as
      "component analysis," is meaningful, even though it is a function of the
      integration path. Moreover, it is shown that the path dependence can be used to
      determine the relation of the contribution of a given interaction to the state of
      the system. To illustrate these conclusions, a simple transformation (Cl- to Br-
      in aqueous solution) is analyzed by use of the Reference Interaction Site Model
      Hypernetted Chain Closure integral equation approach; it avoids the calculational
      difficulties of macromolecular simulation while retaining their conceptual
      complexity. The difference in the solvation free energy between chloride and
      bromide is calculated, and the contributions of the Lennard-Jones and
      electrostatic terms in the potential function are analyzed by the use of suitably
      chosen integration paths. The model is also used to examine the path dependence
      of individual contributions to the double free energy differences (delta delta G
      or delta delta A) that are often employed in free energy simulations of
      biological systems. The alchemical path, as contrasted with the experimental
      path, is shown to be appropriate for interpreting the effects of mutations on
      ligand binding and protein stability. The formulation is used to obtain a better
      understanding of the success of the Poisson-Boltzmann continuum approach for
      determining the solvation properties of polar and ionic systems.

PMID- 7824521
TI  - Pyrrolidone carboxyl peptidase (Pcp): an enzyme that removes pyroglutamic acid
      (pGlu) from pGlu-peptides and pGlu-proteins.
AB  - Pyrrolidone carboxyl peptidase (EC 3.4.11.8) is an exopeptidase commonly called
      PYRase, which hydrolytically removes the pGlu-proteins. pGlu also known as
      pyrrolidone carboxylic acid may occur naturally by an enzymatic procedure or may
      occur as an artifact in proteins or peptides. The enzymatic synthesis of pGlu
      suggests that this residue may have important biological and physiological
      functions. Several studies are consistent with this supposition. PYRase has been
      found in a variety of bacteria, and in plant, animal, and human tissues. For over
      two decades, biochemical and enzymatic properties of PYRase have been
      investigated. At least two classes of PYRase have been characterized. The first
      one includes the bacterial and animal type I PYRases and the second one the
      animal type II and serum PYRases. Enzymes from these two classes present
      differences in their molecular weight and in their enzymatic properties.
      Recently, the genes of PYRases from four bacteria have been cloned and
      characterized, allowing the study of the primary structure of these enzymes, and
      their over-expression in heterelogous organisms. Comparison of the primary
      structure of these enzymes revealed striking homologies. Type I PYRases and
      bacterial PYRases are generally soluble enzymes, whereas type II PYRases are
      membrane-bound enzymes. PYRase II appears to play as important a physiological
      role as other neuropeptide degrading enzymes. However, the role of type I and
      bacterial PYRases remains unclear. The primary application of PYRase has been its
      utilization for some protein or peptide sequencing. Development of chromogenic
      substrates for this enzyme has allowed its use in bacterial diagnosis.

PMID- 7824522
TI  - Protein stability parameters measured by hydrogen exchange.
AB  - The hydrogen exchange (HX) rates of the slowest peptide group NH hydrogens in
      oxidized cytochrome c (equine) are controlled by the transient global unfolding
      equilibrium. These rates can be measured by one-dimensional nuclear magnetic
      resonance and used to determine the thermodynamic parameters of global unfolding
      at mild solution conditions well below the melting transition. The free energy
      for global unfolding measured by hydrogen exchange can differ from values found
      by standard denaturation methods, most notably due to the slow cis-trans
      isomerization of the prolyl peptide bond. This difference can be quantitatively
      calculated from basic principles. Even with these corrections, HX experiments at
      low denaturant concentration measure a free energy of protein stability that
      rises above the usual linear extrapolation from denaturation data, as predicted
      by the denaturant binding model of Tanford.

PMID- 7824523
TI  - Structure and dynamics of the neutrophil defensins NP-2, NP-5, and HNP-1: NMR
      studies of amide hydrogen exchange kinetics.
AB  - The exchange kinetics for the slowly exchanging amide hydrogens in three
      defensins, rabbit NP-2, rabbit NP-5, and human HNP-1, have been measured over a
      range of pH at 25 degrees C using 1D and 2D NMR methods. These NHs have exchange
      rates 10(2) to 10(5) times slower than rates from unstructured model peptides.
      The observed distribution of exchange rates under these conditions can be
      rationalized by intramolecular hydrogen bonding of the individual NHs, solvent
      accessibility of the NHs, and local fluctuations in structure. The temperature
      dependencies of NH chemical shifts (NH temperature coefficients) were measured
      for the defensins and these values are consistent with the defensin structure. A
      comparison is made between NH exchange kinetics, NH solvent accessibility, and NH
      temperature coefficients of the defensins and other globular proteins. Titration
      of the histidine side chain in NP-2 was examined and the results are mapped to
      the three-dimensional structure.

PMID- 7824524
TI  - Estimation of changes in side chain configurational entropy in binding and
      folding: general methods and application to helix formation.
AB  - Theoretical estimations of changes in side chain configurational entropy are
      essential for understanding the different contributions to the overall
      thermodynamic behavior of important biological processes like folding and
      binding. The configurational entropy of any given side chain in any particular
      protein can be evaluated from the complete energy profile of the side chain.
      Calculations of the energy profiles can be performed using the side chain single
      bond dihedrals as the only independent variables as long as the structures at
      each value of the dihedrals are allowed to relax through small changes in the
      valence bond angles. The probabilities of different side chain conformers
      obtained from these energy profiles are very similar to the conformer populations
      obtained by analysis of side chain preferences in the proteins of the Protein
      Data Bank. Also, side chain conformational entropies obtained from the energy
      profiles agree extremely well with those obtained from the Protein Data Bank
      conformer populations. Changes in side chain configurational entropy in binding
      and folding can be computed as differences in conformational entropy because, in
      most cases, the frequency of the rotational oscillation around the energy minimum
      of any given conformer does not appear to change significantly in the reactions.
      Changes of side chain conformational entropy calculated in this way were compared
      with experimental values. The only available experimental data--the effect of
      side chain substitution on the stability of alpha-helices--were used for this
      comparison. The experimental values were corrected to subtract the solvent
      contributions. This comparison yields an excellent agreement between calculated
      and experimental values, validating not only the theoretical estimates but also
      the separability of the entropic contributions into configurational terms and
      solvation related terms.

PMID- 7824525
TI  - Intrinsic pKas of ionizable residues in proteins: an explicit solvent calculation
      for lysozyme.
AB  - Molecular dynamics simulations of triclinic hen egg white lysozyme in aqueous
      solution were performed to calculate the intrinsic pKas of 14 ionizable residues.
      An all-atom model was used for both solvent and solute, and a single 180 ps
      simulation in conjunction with a Gaussian fluctuation analysis method was used.
      An advantage of the Gaussian fluctuation method is that it only requires a single
      simulation of the system in a reference state to calculate all the pKas in the
      protein, in contrast to multiple simulations for the free energy perturbation
      method. pKint shifts with respect to reference titratable residues were evaluated
      and compared to results obtained using a finite difference Poisson-Boltzmann
      (FDPB) method with a continuum solvent model; overall agreement with the
      direction of the shifts was generally observed, though the magnitude of the
      shifts was typically larger with the explicit solvent model. The contribution of
      the first solvation shell to the total charging free energies of the titratable
      groups was explicitly evaluated and found to be significant. Dielectric shielding
      between pairs of titratable groups was examined and found to be smaller than
      expected. The effect of the approximations used to treat the long-range
      interactions on the pKint shifts is discussed.

PMID- 7824526
TI  - Microtube batch protein crystallization: applications to human immunodeficiency
      virus type 2 (HIV-2) protease and human renin.
AB  - For therapeutically relevant targets, the evaluation of enzymes in complex with
      their inhibitors by cocrystallization and high resolution structural analysis has
      become a vital component of structure-driven drug design and development. Two
      approaches, hanging drop vapor diffusion and a novel microtube batch method, were
      utilized in parallel to grow crystals of recombinant HIV-2 protease and
      recombinant human renin in complex with inhibitors. In the case of HIV-2 protease
      in complex with a reduced amide inhibitor, crystallization was achieved only by
      the microbatch method. In the case of human renin, the addition of precipitant
      was required for crystal growth. The microbatch method described here is a useful
      supplementary or alternative approach for screening parameters and generating
      crystals suitable for high resolution structural analysis.

PMID- 7824527
TI  - Monthly prostaglandin bibliography prepared by Sheffield University Biomedical
      Information Service.

PMID- 7824528
TI  - Cellular signalling of PGE2 and its selective receptor analogue sulprostone in
      rabbit cortical collecting duct.
AB  - We have documented new observations with respect to PGE2 action in the rabbit
      CCD. (1) PGE2 can inhibit both cAMP and vasopressin-induced water flow, depending
      on the sequence of PGE2 addition with respect to vasopressin or cAMP. (2) PGE2
      inhibition of vasopressin or cAMP-stimulated water flow can be reversed with
      staurosporine. Thus, PGE2 inhibits vasopressin-stimulated water flow by
      activation of PKC and (3) PGE2 induces release of calcium from intracellular
      stores. These results strongly suggest the presence of a PGE2 receptor coupled to
      PIP2 hydrolysis. PGE2 mediated increases in cytosolic calcium are responsible for
      the inhibitory action of PGE2 on sodium transport. While stimulation of cAMP
      production by PGE2 may contribute to the inhibition of sodium transport, it is
      not required since in the presence of 8-CPTcAMP, PGE2 still decreases sodium
      transport. The effect of PGE2 on sodium transport is pertussis toxin insensitive
      and is unlikely to be mediated by an inhibitory G protein. Using PGE2 and one of
      its selective analogues, sulprostone, we have provided evidence for functionally
      distinct PGE2 receptors. Separate PGE2 receptor subtypes appear to be coupled to
      separate transport processes. These receptor subtypes may correspond to the EP1,
      EP2 and EP3 receptors described earlier in smooth muscle. Thus, an EP2 like
      receptor stimulates cAMP generation and water reabsorption while an EP1 like
      receptor increases [Ca++]i and inhibits sodium reabsorption. Finally, an EP3
      receptor, equivalently activated by sulprostone and PGE2, may couple to Gi and
      mediate pertussis toxin sensitive inhibition of vasopressin-stimulated water
      flow.

PMID- 7824529
TI  - Thromboxane A2 biosynthesis inhibitors: synthesis and evaluation of
      pyrazolotriazinyl alkanoic acids.
AB  - A novel series of (6-aryl-4-oxo-pyrazolo 2,3-d] [1,2,5] triazin-3-yl) alkanoic
      acids was synthesized and evaluated in vitro as thromboxane A2 (TXA2)
      biosynthesis inhibitors. The experiments were carried out using arachidonic acid
      (32.8 microM) as a substrate and horse platelet microsomes (HPM) as sources of
      TXA synthetase. TXB2, a stable breakdown product of TXA2, was determined by
      radioimmunoassays (RIA). The substances under study, at concentrations ranging
      from 1.10(-6) M to 1.10(-4) M, significantly inhibited the biosynthesis of TXA2
      in vitro. This activity was found to be dose-dependent, the potency of which
      could be related to structural features of the molecules. Compound 3b, bearing a
      butanoic side chain in the 3-position and a 4-chloro phenyl ring in the 6
      position of the bicyclic system, was the most active derivative in in vitro
      enzyme inhibition (ID50 = 2.81 x 10(-5) M). Comparison of the spatial
      configurations of prostaglandin H2 (PGH2 and 3b displayed a good correlation
      between essential structural moieties of both molecules. In addition, conceptual
      model for the PGH2 and TX synthetase interactions was applied to compound 3b.

PMID- 7824530
TI  - Inhibitory effect of ONO-1078 on specific binding of peptide leukotrienes to
      human lung crude membrane.
AB  - We investigated the effects of ONO-1078, a newly synthesized peptide leukotriene
      (p-LT antagonist, on the specific binding of radiolabelled [3H]-LTC4, [3H]-LTD4
      and [3H]-LTE4 to a human lung crude membrane fraction (HLMF). The binding assay
      was performed under conditions in which [3H]-LTC4 and [3H]-LTD4 were not
      metabolized by HLMF; that is, the metabolism of LTC4 to LTD4 or LTE4 was almost
      completely prevented by pretreating HLMF with 5 mM acivicin at 37 degrees C for
      180 min, and metabolism of LTD4 to LTE4 was inhibited by including 5 mM L
      cysteine and 5 mM glycine in the assay. [3H]-LTD4 specific binding was potently
      and concentration-dependently dissociated by ONO-1078. Its potency was 180-fold
      stronger than that of FPL 55712, a standardized p-LT antagonist, whereas high
      concentrations of ONO-1078 similar to those of FPL 55712 were required to inhibit
      [3H]-LTC4 specific binding. The rank order of the inhibitory potencies of p-LT
      agonists and antagonists for [3H]-LTD4 specific binding was LTD4 > ONO-1078 >
      LTE4 > LTC4 > FPI 55712. On the other hand, not only high concentrations of ONO
      1078 and FPL 55712 but also more than a 100-fold excess of unlabelled LTE4 was
      required to inhibit [3H]-LTE4 specific binding, indicating that the binding sites
      do not appear to be receptors of LTE4. From these results, it is suggested that
      ONO-1078 is a highly potent LTD4 antagonist which is expected to be very
      effective on bronchial asthma.

PMID- 7824531
TI  - Spinal cord blood flow during prostaglandin E1 induced hypotension.
AB  - To evaluate the effect of prostaglandin E1 (PGE1) induced hypotension on spinal
      blood flow (SBF) during spinal surgery, SBF was measured under isoflurane
      anaesthesia by the heat clearance method in 10 patients with spinal tumour. An
      initial dose of 0.1 microgram/kg/min of PGE1 was administered intravenously after
      spinal opening and the dose was adjusted to maintain the mean arterial blood
      pressure (MAP) at about 60 mmHg. PGE1 was discontinued at the completion of the
      operative produces. After starting PGE1, MAP and rate pressure product (RPP)
      decreased significantly compared with preinfusion values (P < 0.01), and the
      hypotensive effect of PGE1 remained constant at 60 min after its discontinuation.
      Heart rate (HR) did not change throughout the study. SBF showed no change over
      the course of PGE1 induced hypotension (preinfusion: 47.8 +/- 21.7 ml/100 g/min,
      at 15 min: 41.2 +/- 16.9 ml/100 g/min, at 30 min: 40.4 +/- 16.8 ml/100 g/min, and
      at 60 min: 46.1 +/- 16.3 ml/100 g/min, respectively). These results suggest that
      PGE1 may be a useful drug for hypotensive anaesthesia in surgery for spinal cord
      tumours because PGE1 maintained SBF.

PMID- 7824532
TI  - Modulation of lipoxidase activity by urokinase-type plasminogen activator.
AB  - Malignant cells show increased urokinase (UK) activity and decreased peroxidation
      of essential fatty acids (EFA). In order to explore this phenomenon the effect of
      UK on the lipoxidase activity was spectrophotometrically investigated. Decreased
      lipoxidase activity was obtained with increased UK concentrations (r = -1.000, p
      < 0.0001). This proteolytic effect of UK on lipoxidase was eliminated with the
      addition of the UK inhibitor leupeptin. These results suggest that the increase
      in UK activity in malignant cells may decrease the lipoxidase activity and thus
      peroxidation of EFA. The effectiveness of a given EFA in killing cancer cells
      would therefore depend on the modulation of the lipoxidase activity by the UK
      type plasminogen activator.

PMID- 7824533
TI  - Modulation of the transcellular metabolism of 12(S)HETE by 10-11 reductase
      activity in cultured rat aortic smooth muscle cells.
AB  - Cultured rat aortic smooth muscle cells (SMC) metabolize
      12(S)hydroxyeicosatetraenoic acid (12(S)HETE) by two different pathways; beta
      oxidation leading to 16:3(8-OH), and 10-11 reductase activity producing 20:3(12
      OH) which is beta-oxidized to 16:2(8-OH). In this work, we demonstrate that 10-11
      reductase activity is modulated in cultured rat aortic SMC as a function of cell
      state (proliferating vs quiescent) and stimulated by serum. Most of the 20:3(12
      OH) is recovered in the incubation medium but a significant part is esterified
      into phospholipids. By comparison with its parent compound, 12(S)HETE, 20:3 (12
      OH) is mainly incorporated into phosphatidyl-choline and phosphatidyl
      ethanolamine, suggesting that it may affect cellular functions. Taken together,
      these findings may be relevant to the effects of 12(S)HETE on vascular SMC
      functions related to atherosclerotic development.

PMID- 7824534
TI  - Prostaglandin F2 alpha modulates responses of single cultured mesangial cell to
      arginine vasopressin.
AB  - The role of prostaglandin F2 alpha (PGF2 alpha) interaction with arginine
      vasopressin (AVP) in modulating intracellular Ca2+ homeostasis was studied.
      Examinations were done on single cultured mesangial cells loaded with fura-2.
      Pretreatment of cultured mesangial cells during 1 min with different
      concentrations of PGF2 alpha (10(-5)-10(-8) M) caused a significant prolongation
      of [Ca2+]i transients after subsequent AVP applications. The observed effect of a
      prolonged sustained phase was not influenced by the temporal sequence of AVP
      stimulation after preincubation with PGF2 alpha: the signal was modulated in
      nearly the same way after 5 min delay as after nearly simultaneous application of
      AVP and PGF2 alpha. Measurements in Ca(2+)-free medium showed that the prolonged
      sustained phase of [Ca2+]i transients after AVP applications in cells pretreated
      with PGF2 alpha was mostly due to Ca2+ release from intracellular store(s).
      Pretreatment of the cells with PGF2 alpha also greatly enhanced the % of AVP
      responsive cells. Even at concentrations of AVP as low as 10(-10) M about 30% of
      cells pretreated with PGF2 alpha responded with the fast [Ca2+]i rise. Thus,
      present studies showed that PGF2 alpha specifically modulates [Ca2+]i transients
      after AVP stimulation and enhances sensitivity of mesangial cells to AVP. The
      results help to identify PGF2 alpha participation in the cellular regulatory
      mechanisms of microcirculation and filtration in the kidney.

PMID- 7824535
TI  - Beneficial effect of eicosapentaenoic and docosahexaenoic acids in the management
      of systemic lupus erythematosus and its relationship to the cytokine network.
AB  - Systemic lupus erythematosus (SLE) is a chronic inflammatory condition
      characterised by arthritis, cutaneous rash, vasculitis, and involvement of
      central nervous system, renal and cardiopulmonary manifestations. Abnormalities
      in the cytokine network is believed to be involved in the pathobiology of this
      condition. The n-3 fatty acids such as eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA) can suppress T-cell proliferation and the production
      of interleukin-1, interleukin-2, and tumor necrosis factor by these cells both in
      vitro and in vivo. Oral supplementation of EPA and DHA induced prolonged
      remission of SLE in 10 consecutive patients without any side-effects. These
      results suggest that n-3 fatty acids, EPA and DHA, are useful in the management
      of SLE and possibly, other similar collagen vascular diseases.

PMID- 7824536
TI  - Influence of nootropic and antidepressive drugs on open field and running wheel
      behavior in spontaneously high and low active mice.
AB  - Mice differentiated by their running wheel activity into low and high active
      animals were chronically treated with the nootropics meclophenoxate, piracetam,
      vinpocetine, methylglucaminorotate, and the antidepressants lithium, desipramine,
      amitriptyline, and clomipramine. The influence of chronic drug treatment on
      running-wheel activity and open field locomotor behaviour was analyzed. Whereas
      with antidepressants rather sedative effects were observed in both activity
      types, the effects of nootropics were different in high and low active mice.
      Running-wheel scores increased in low active mice but decreased in high-active
      animals with an improvement in efficiency of locomotor behaviour in the open
      field of these mice after chronic nootropic treatment. In general, the effects of
      antidepressants seemed to be more uniform than those of the nootropics used.

PMID- 7824537
TI  - Strain-related differences in adenosine receptor density and in behavioral
      sensitivity to adenosine analogs in mice.
AB  - The behavioral effects of the adenosine agonists 5'-N-ethylcarboxamidoadenosine
      (NECA) was investigated in two strains of inbred mice, CD1 and CBA. NECA dose
      dependently reduced spontaneous locomotor activity with similar potency (ED50 =
      36 +/- 1.5 and 36 +/- 1.1 nmol/kg IP for CBA and CD1 mice, respectively) and
      efficacy (> 90% at 100 nmol/kg) in the two strains. One nmol/kg NECA, an
      ineffective dose in CBA mice, exerted a significant stimulant action in CD1 mice.
      In saturation experiments, no differences were found in the density or in the
      affinity of striatal A2a receptors labeled with [3H]NECA. A strain-related
      difference was found in the density of striatal A1 receptors labeled with
      [3H]CCPA. In CBA mice, the Bmax value was 32% less than in CD1 mice (0.646 +/-
      0.037 and 0.951 +/- 0.073 pmol bound/mg protein, respectively, p < 0.05). No
      differences in [3H]CCPA binding parameters were found in cortical and hippocampal
      membranes obtained from the two strains, whereas a higher density of A1 binding
      sites was found in the cerebellum of CBA mice. The present results show a close
      correlation between binding studies and the depressant action of NECA and present
      evidence for strain-related differences in regional distribution of central
      adenosine receptors and in behavioral response to purinergic drugs.

PMID- 7824538
TI  - The brain tryptophan hydroxylase activity in the sleep-like states in frog.
AB  - The activity of the rate-limiting enzyme of serotonin biosynthesis, tryptophan
      hydroxylase, was determined in the brain stem in active awake frogs, and frogs in
      three sleep-like states: with plastic muscle tone (SLS-1), with rigid muscle tone
      (SLS-2), and with relaxed muscle tone (SLS-3). Significant decrease in the enzyme
      activity has been found in frogs in SLS-1 and SLS-2 compared to awake animals.
      The development in frogs a cataleptic-like immobility after treating the animals
      with rhythmic lighting was accompanied with a decrease in the brain tryptophan
      hydroxylase activity. These results provide strong evidence for the involvement
      of the brain serotonin in frogs in the control of evolutionary ancient sleep-like
      states, probably by the regulation of muscle tone.

PMID- 7824539
TI  - Anxiolytic-like effect of paroxetine in a rat social interaction test.
AB  - The effects of short- and long-term administration of the selective serotonin
      reuptake inhibitor paroxetine were investigated in a rat social interaction test.
      A single administration of paroxetine at oral doses of 0.3, 1, 3 and 10 mg/kg had
      no effect on social interaction between pairs of male rats under bright light
      (high anxiety) conditions. After 21 days of daily administration, paroxetine
      given orally at 3 mg/kg significantly (p < 0.01) increased the time spent in
      social interaction by pairs of rats tested under the same conditions, with no
      effect on locomotor activity, indicating an anxiolytic-like effect. The magnitude
      of increase (+97%) was comparable to that seen after a single dose of
      chlordiazepoxide (4 mg/kg orally). Although there was also an increase in time
      spent in social interaction after 21 days of repeated oral administration of
      paroxetine at 0.3, 1, and 10 mg/kg (+44, +56, and +54% increases, respectively),
      statistical significance was not achieved. These results indicate that in the
      long term paroxetine has an anxiolytic action, and thus support the clinical
      evidence for its therapeutic use in the treatment of anxiety disorders in
      addition to its established role as an antidepressant.

PMID- 7824540
TI  - Long-term administration of dexfenfluramine to genetically obese (ob/ob) and lean
      mice: body weight and brain serotonin changes.
AB  - The weight-reducing and brain 5-HT-depleting properties of dexfenfluramine (DFEN)
      or dexnorfenfluramine (DNOR) were measured in genetically obese (ob/ob) and lean
      mice. These agents were infused for 14 days via osmotic minipumps to mice fed
      either a low fat or a moderate fat diet. Weight loss was observed in only the
      obese mice, with DNOR more potent than DFEN. At the end of 14 days, neither agent
      caused a consistent change in either plasma glucose or corticosterone
      concentrations, although some effects of diet and differences between batches of
      mice were apparent. The levels of brain 5-HT, or of paroxetine binding that
      correlates with 5-HT level, were reduced by 24 mg DFEN/kg/day, a decline that
      persisted for at least 14 days after the end of treatment. Plasma and brain
      concentrations of DFEN and DNOR were measured on the last day of pump function.
      DNOR accounted for about 30% of the total drug + metabolite content, a ratio
      comparable to that in human plasma. Brain concentrations exceeded plasma by 10
      fold at 6 mg DFEN/kg/day and by 17-fold at 24 mg DFEN/kg/day. The levels were
      higher in mice fed the moderate-fat compared with the low-fat diet. Depletions in
      brain 5-HT parameters were found only in the high-dose groups, and at brain total
      levels above about 20 microM.

PMID- 7824541
TI  - The role of adrenoreceptors in control of stereotyped oral behavior in restricted
      fed fowls.
AB  - Effects on environmentally induced oral stereotypies (object pecking and drinker
      directed activity) of preferential antagonists and agonists of adrenoreceptor
      subtypes were examined in individually caged broiler breeder fowls subjected to
      chronic food restriction. Three drugs in each category were injected
      intravenously at three doses, and their effects compared with a saline control
      treatment. With the antagonists, object pecking was suppressed more by prazosin
      (alpha 1) and propranolol (beta) than by yohimbine (alpha 2), while drinker
      directed activity showed delayed stimulation with yohimbine and propranolol. With
      the agonists, drinker-directed activity was suppressed more by clonidine (alpha
      2) than by isoproterenol (beta) and phenylephrine (alpha 1), while object pecking
      was inhibited by the high doses of clonidine and isoproterenol but showed delayed
      stimulation with the low dose of clonidine and (nonsignificantly) the high dose
      of phenylephrine. Initial suppression of both oral stereotypies by the high doses
      of yohimbine and isoproterenol, and high and medium doses of clonidine, may have
      been due to sedation, because in those instances it coincided with increased
      sitting, an activity not normally seen. Increased standing with clonidine and the
      medium dose of yohimbine may also reflect sedation. When there were no
      significant increases in sitting or standing to indicate sedation, responses of
      both stereotypies were essentially the same with all three adrenoreceptor
      subtypes; i.e., object pecking was inhibited by the antagonist but not the
      agonist, while drinker-directed activity was inhibited by the agonist but not the
      antagonist. It is concluded that alpha 1, alpha 2, and beta adrenoreceptors are
      all implicated in expression of these stereotypes, and that the two activities
      may be differentially controlled.

PMID- 7824542
TI  - Participation of opiatergic, GABAergic, and serotonergic systems in the
      expression of copulatory analgesia in male rats.
AB  - Copulation in the male rat provoked an abrupt and significant rise in the
      threshold to induce vocalization by electrical shock to the tail (copulatory
      analgesia, CA). The possible effect on CA of the intrathecal (IT) administration
      of receptor antagonists to neurotransmitters participating in nociception was
      ascertained in this study. CA was significantly reduced, though not abolished, by
      IT injections of either naloxone, picrotoxin, or methysergide, but not by
      strychnine or yohimbine. This analgesic effect was achieved without significantly
      altering copulatory behavior. Results suggest that both brain and spinal systems
      participate in the development of CA. Brain effects would be mediated by
      descending serotonergic fibers, although intrinsic spinal systems would involve
      both opiate and GABA interneurons.

PMID- 7824543
TI  - Tardive dyskinesia: behavioral effects of repeated intracerebroventricular
      haloperidol injections in rats do not confirm the kindling hypothesis.
AB  - The development of tardive dyskinesia (TD) has been claimed to be the result of a
      kindling-like mechanism. This hypothesis is based on studies suggesting that
      intermittent neuroleptic treatment may increase the risk of irreversible TD in
      humans and persistent vacuous chewing movements (VCM) in rats. We investigated
      the effect of daily intracerebroventricular (ICV) injections of haloperidol 37.5
      micrograms/kg for 12 weeks in rats. Behavior was recorded immediately after the
      first injection, with 2 weeks intervals during treatment, and 3 weeks after drug
      withdrawal. In a separate experiment, rats received one injection of haloperidol
      IP. The acute effect of haloperidol ICV was an immediate increase in VCM and a
      reduction in motor activity that lasted for approximately 2 h. The behavioral
      response to haloperidol IP was similar, but of much longer duration. No
      significant behavioral changes were observed either 24 h after the ICV injections
      during haloperidol treatment or 3 weeks after drug withdrawal. The results did
      not support the hypothesis that kindling is important for the development of TD.

PMID- 7824544
TI  - Can posttreatment with the selective dopamine D2 antagonist, YM-09151-2, inhibit
      induction of methamphetamine sensitization? Evaluation by ambulatory activity in
      mice.
AB  - Effects of YM-09151-2; cis-N-(1-benzyl-2-methyl pyrrolidin-3-yl)-5-chloro-2
      methoxy-4-methylaminobenzamide (YM), a potent and selective dopamine D2
      antagonist, on sensitization to methamphetamine (MAP) were investigated by means
      of ambulatory activity in mice. YM (0.003-0.03 mg/kg SC) reduced not only the
      acute ambulation-increasing effect of MAP (2 mg/kg SC) but also the induction of
      MAP sensitization when it was simultaneously administered with MAP in the
      repeated administration at 3-4 day intervals. Moreover, the post 3-h treatment
      with YM (0.01 and 0.03 mg/kg) following each MAP administration, at which time
      the acute ambulation-increasing effect of MAP almost disappeared, significantly
      and dose dependently inhibited the induction of MAP sensitization. The post 24-h
      treatment with YM did not show such effect. The present results suggest that
      blockade of the dopamine D2 receptors during postearly period following MAP
      administration is responsible for protecting the induction of MAP sensitization
      by means of ambulatory activity in mice.

PMID- 7824545
TI  - The effects of melatonin on isolation distress in chickens.
AB  - Melatonin (0.1-1.0 mg/kg) reduced isolation-induced distress vocalizations (DVs)
      in young domestic chickens in a dose-dependent manner. This effect was unaffected
      by the administration of d-amphetamine (1.0 mg/kg) suggesting that melatonin's
      effects were not merely due to fatigue. The melatonin reduction in DVs was not
      naloxone reversible, indicating an action independent of the endogenous opioid
      system. However, chronic pretreatment with naltrexone facilitated the melatonin
      effect, suggesting a complex relationship between melatonin and the endogenous
      opioids in regulating distress vocalizations. Chickens exhibited a marked
      reduction in DVs when isolation chambers were darkened, suggesting endogenous, as
      well as exogenous, melatonin mediation of isolation distress; however;
      pinealectomy only partially reversed the darkness effect. Pinealectomized
      animals, like control animals, exhibited a reduction in DVs following melatonin
      treatment; however, the melatonin effect was shorter lasting. The implications
      that these results may have for socialization and emotional distress are
      discussed.

PMID- 7824546
TI  - Differential effects of various antiinflammatory drugs on theophylline
      neurotoxicity.
AB  - The purpose of the present investigation was to evaluate whether antiinflammatory
      drugs affect the pharmacodynamics of theophylline-induced seizures. Adult male
      Lewis rats were treated with either dexamethasone (DEX), hydrocortisone (HYD),
      ibuprofen (IBU), or mefenamic acid (MFA), for 4 consecutive days. On the fourth
      day they received a constant infusion of theophylline (2 mg/min IV) until the
      onset of maximal seizures. Then, blood and cerebrospinal fluid (CSF) were
      obtained for theophylline concentration determinations by HPLC. It was found that
      pretreatment with the corticosteroids DEX and HYD elevated the CSF theophylline
      concentration required to induce maximal seizures in comparison to the untreated
      rats (242 +/- 6, 232 +/- 6, and 203 +/- 10 mg/l, respectively, n = 10, p < 0.05).
      MFA also increased the CSF theophylline concentration at that end-point in
      comparison to the controls (p < 0.01), whereas pretreatment with IBU had no
      effect (280 +/- 10 MFA, 225 +/- 9 IBU vs. 220 +/- 8 controls, n = 12). The data
      suggests that concomitant treatment with antiinflammatory drugs, together with
      theophylline, do not increase the risk for theophylline-induced seizures.
      Moreover, in certain cases they may elevate the seizure threshold and protect
      against these hazardous episodes.

PMID- 7824547
TI  - High-dose peripheral inositol raises brain inositol levels and reverses
      behavioral effects of inositol depletion by lithium.
AB  - Lithium (Li) reduces brain inositol levels. Berridge has suggested that this
      effect is related to Li's mechanism of action. It had previously been shown that
      pilocarpine causes a limbic seizure syndrome in lithium treated rats, and that
      these lithium-pilocarpine seizures are reversible by intracerebroventricular
      inositol administration to rats. We now show that although inositol passes the
      blood-brain barrier poorly, large doses of intraperitoneal (IP) inositol can also
      reverse Li-pilocarpine seizures. Using gas chromatography, IP inositol can raise
      brain inositol levels. Demonstration that inositol enters brain after peripheral
      administration provides a basis for possible pharmacological intervention in
      psychiatric disorders at the level of second messengers linked to the
      phosphatidylinositol cycle.

PMID- 7824548
TI  - The preferential dopamine autoreceptor antagonist (+)-UH232 antagonizes the
      positive reinforcing effects of cocaine and d-amphetamine in the ICSS paradigm.
AB  - The dopamine autoreceptor and D3 preferring antagonist [cis-(+)-5-methoxy-1
      methyl-2-(di-n-propylamino)tetralin] (+)-UH232, exerts weak stimulatory effects
      when tested in locomotor activity experiments using habituated animals. (+)-UH232
      also blocks d-amphetamine-, cocaine-, and apomorphine-induced hyperactivity, but
      fails to induce catalepsy. Thus, the behavioral effects of (+)-UH232 appear to be
      dependent upon the baseline activity of the animal. The antagonistic properties
      of (+)-UH232 were studied in the intracranial self-stimulation (ICSS) technique
      in the rat. (+)-UH232 and haloperidol produced inhibitory effects over a wide
      dose range. Cocaine, GBR12909 and d-amphetamine clearly lowered ICSS thresholds,
      indicating stimulatory effects. (+)-UH232 antagonized the stimulatory effects of
      cocaine, GBR12909, and d-amphetamine, whereas haloperidol, at a dose producing an
      inhibition similar to (+)-UH232, was significantly weaker in antagonizing cocaine
      or d-amphetamine-induced stimulation. This difference between (+)-UH232 and
      haloperidol with respect to stimulant-blocking ability, support the concept that
      the effects of (+)-UH232 are not representative of either classical DA agonists
      or DA antagonists.

PMID- 7824549
TI  - Permanent dopaminergic alterations in the n. accumbens after prenatal stress.
AB  - It has been suggested that stress during the initial stages of human life may
      serve as a predisposing factor to mental illness. Recently, we reported that in
      pregnant rats, stress induces an increase of behavioral depression in the female
      offsprings when adult. This article describes the effect of prenatal stress on
      central dopaminergic transmission during adulthood. The offspring of stressed
      mothers showed an increase of behavioral depression in the Porsolt test and a
      reduction of DOPAC, HVA, and DOPAC/DA index in the n. accumbens. The effect on
      the right accumbens was more marked than on the left. A great body of information
      exists to suggest that depression is related to a decrease of dopaminergic
      neurotransmission, and the present data provide new evidence in support of the
      hypothesis that maternal stress during gestation increases the risk of depression
      in the offspring. We are also reporting a hitherto uncommented relationship
      between behavioral depression in the Porsolt test and the decrease of dopamine
      transmission in the n. accumbens.

PMID- 7824550
TI  - Diazepam withdrawal increases [3H]-5-HT release from rat amygdaloid slices.
AB  - The release of [3H]-5-HT and [14C]-GABA from hippocampal and amygdaloid slices
      was studied in a group of rats in which an anxiogenic response had been found on
      withdrawal of chronic diazepam treatment (2 mg/kg/day for 21 days). Basal release
      and uptake of [3H]-5-HT and [14C]-GABA and K(+)-evoked release of [14C]-GABA were
      not significantly changed in either brain region following diazepam withdrawal.
      However, there was a significant increase in K(+)-evoked [3H]-5-HT release from
      the amygdala, but not from the hippocampal, slices. These results demonstrate
      that increased 5-HT release from the hippocampus is not necessary to mediate the
      anxiogenic withdrawal response, and that raised 5-HT release in the amygdala may
      be sufficient to mediate this response. The results are discussed with respect to
      conditions, such as noise during diazepam treatment, that might produce
      regionally specific changes in 5-HT tone and hence modify the pattern of changes
      found during diazepam withdrawal.

PMID- 7824551
TI  - The effects of physostigmine and scopolamine on memory for food caches in the
      black-capped chickadee.
AB  - The possible effects of anticholinesterases on the central nervous system and, in
      particular, on learning and memory, have generated considerable interest. Food
      caching in the black-capped chickadee is an excellent natural paradigm of spatial
      working memory. Its susceptibility to cholinergically active drugs was explored
      in the present study. Our ultimate objective was to use food caching as a natural
      paradigm for the study of the consequences in birds of sublethal exposure to
      anticholinesterase insecticides. Biochemical analyses showed that administration
      of the anticholinesterase physostigmine (eserine) led to a short-lived effect,
      with recovery of brain cholinesterase levels already underway 5 min after an
      intramuscular injection. Birds administered the anticholinergic scopolamine
      before caching demonstrated significantly impaired recall compared to birds given
      physostigmine. Birds given saline only had an intermediate performance. Giving
      the drugs between caching and recovery had no measurable effect. These findings
      suggest that effects of cholinergic agents on cache recovery in chickadees are
      comparable to their effects in tests of working memory in mammals.

PMID- 7824552
TI  - Age effects on chronic tolerance to ethanol hypnosis and hypothermia.
AB  - Male Fischer 344 rats of three different ages (young, 4 months; middle, 13
      months; and old, 25 months) were tested for their hypnotic and hypothermic
      response to a 3.5 g/kg dose of ethanol on day 1 and after an 8-day exposure to
      4.0 g/kg of ethanol administered via intragastric intubation. All three age
      groups displayed, to a similar extent, an increased rate of blood ethanol
      disappearance (metabolic tolerance) on day 10 and day 16, as compared to day 1.
      Both young and middle-age rats demonstrated tolerance to ethanol hypothermia, but
      older rats did not. The same test dose of ethanol (3.5 g/kg, IP) administered on
      day 16, after a 5-day interval with no ethanol, produced a hypnosis response
      similar to that observed on day 1 (no tolerance), but the response to ethanol
      hypothermia was still significantly reduced over the day 1 and day 10 value in
      young and middle-age rats, suggesting a persistence and intensification of
      tolerance to hypothermia over the 5-day rest interval. However, tolerance to
      ethanol hypothermia was not observed in old rats. Thus, the effects of age on the
      development of chronic functional tolerance were complex and depended upon the
      test measure used.

PMID- 7824553
TI  - Naloxone's effects on operant responding depend upon level of deprivation.
AB  - Naloxone's effects on initiation, maintenance, and maximal response effort to
      acquire food were examined in rats maintained under different levels of food
      deprivation. In Experiment 1, naloxone was administered SC to rats responding
      under an FR 80 (first pellet) FR 3 (subsequent pellets) reinforcement schedule.
      Naloxone did not increase time to acquire the first pellet. Naloxone's
      suppression of subsequent intake and lowest effective dose were inversely related
      to level of deprivation. In Experiment 2, rats responded for food under a
      Progressive Ratio 2 reinforcement schedule. Breakpoint was lowered only when rats
      were maintained with free access to food. Decreases in response and running rate
      were inversely related to deprivation level. Results are consistent with the
      hypothesis that opioids are involved in the maintenance but not the initiation of
      feeding.

PMID- 7824554
TI  - Antiemetic effects of 5-HT1A agonists in the pigeon.
AB  - Ditolyguanidine (DTG) induced a dose-dependent emetic response in pigeons, with
      100% of the birds vomiting after 5.6 mg/kg. Retching and vomiting originally
      induced by DTG could be conditioned to the test situation. Both the unconditioned
      and conditioned emetic responses were dose-dependently blocked by 8-hydroxy-(di-n
      propylamino)tetralin (8-OH-DPAT) and LY228729, agonists at the 5-HT1A subtype of
      serotonin receptor, but not by the 5-HT3, antagonist tropisetron. Higher doses
      (0.25-0.5 mg/kg) of tropisetron exhibited intrinsic emetic activity which could
      also be prevented by 8-OH-DPAT. NAN-190, a putative 5-HT1A partial agonist,
      produced both an antiemetic response when administered before DTG and also
      attenuated the antiemetic effects of 8-OH-DPAT. Pentobarbital blocked the
      conditioned, but not the unconditioned DTG-induced emesis. These results support
      the possibility that 5-HT1A agonists exhibit antiemetic activity against a broad
      range of emetic stimuli, including conditioned vomiting which is usually
      resistant to pharmacological attenuation.

PMID- 7824555
TI  - Effects of early protein malnutrition and environmental stimulation upon the
      reactivity to diazepam in two animal models of anxiety.
AB  - In order to investigate the effects of early protein malnutrition and
      environmental stimulation upon the response to the anxiolytic properties of
      diazepam, two animal models of anxiety (elevated plus-maze and light-dark
      transition tests) were used. Rats were malnourished by feeding their dams a 6%
      protein diet during the lactation period (0-21 days of age) while well-nourished
      controls received a 16% protein diet. From 21 to 70 days of age all rats received
      a balanced lab chow diet. Environmental stimulation consisted of 3-min daily
      handling from birth to 70 days of age. Additional stimulation was provided from
      21 to 70 days of age by rearing the rats in an enriched living cage. Eight groups
      of rats were studied in a 2 (malnourished or well-nourished) x 2 (stimulated or
      nonstimulated) x 2 (diazepam or vehicle) design. At 70 days of age, independent
      groups of rats treated with diazepam (2.5 mg/kg, IP) or vehicle were submitted to
      testing in the elevated plus-maze or light-dark transition procedures. The
      results showed that both diazepam and environmental stimulation reduced anxiety
      in the elevated plus-maze; stimulation changed the anxiolytic response to
      diazepam and the two diet conditions altered differentially the response to both
      pharmacological and stimulation procedures. These results suggest that
      environmental stimulation can affect differentially the behavioral response of
      malnourished and well-nourished rats treated with diazepam.

PMID- 7824556
TI  - Effects of electroconvulsive shock on the retention of cocaine-induced
      conditioning.
AB  - The purpose of these studies was to determine if ECS is capable of preventing the
      retention of cocaine-induced conditioned increases in locomotor behavior. One
      group of rats (paired) was injected with 40 mg/kg of cocaine immediately before a
      30 min exposure to a locomotor monitoring chamber while the other group
      (unpaired) was injected with saline prior to a similar exposure. One hour
      following return to their home cages, the paired rats were injected with saline
      while the unpaired animals were injected with 40 mg/kg of cocaine. On day 2, both
      groups were injected with 10 mg/kg of cocaine and returned to the test apparatus.
      The presence of conditioned cocaine effects are indicated by enhanced locomotor
      output in the paired group relative to the unpaired group on day 2. ECS delivered
      immediately following training on day 1 was effective in preventing the retention
      of conditioning. ECS delivered 1 h prior to training, 1 h after or 1 h before on
      day 2 were ineffective. Cocaine-induced conditioning appears to involve
      associative learning that can be disrupted by ECS delivered immediately following
      training.

PMID- 7824557
TI  - Differences in ligand binding and phosphoinositide turnover between M1 muscarinic
      receptor gene transfected cells and mouse and rat brain membranes.
AB  - The present study describes some unexpected receptor mediated effects of N
      methylcarbamylcholine on mouse M1 muscarinic receptor gene transfected cell line
      (M1Y1) that were not evident from biochemical studies with mouse and rat brain
      tissue where N-methylcarbamylcholine exhibited only nicotinic properties.
      Although N-methylcarbamycholine was devoid of muscarinic properties in mouse and
      rat brain preparations, as determined by phosphoinositide turnover and inhibition
      of [3H]QNB binding, it exhibited significant muscarinic characteristics in the
      transfected M1Y1 cell line. At a concentration of 10(-6) M or greater, N
      methylcarbamycholine caused a transient increase in intracellular Ca2+ of 50 s
      duration that was reversible by atropine or pirezepine. The Ca(2+)-transient was
      not elicited by other nicotinic agents such as nicotine and N,N
      dimethylcarbamylcholine, a close analogue of N-methylcarbamylcholine, with
      comparable affinity for nicotinic receptors and devoid of muscarinic activity. N
      Methylcarbamylcholine also stimulated phosphoinositide turnover in M1Y1 cells
      with an estimated EC50 value 10 times greater than that of carbachol, and the
      effect was blocked by atropine. Both carbachol and N-methylcarbamycholine
      inhibited [3H]QNB binding in a concentration-dependent manner; however, the IC50
      for carbachol was over two orders of magnitude greater than that observed in
      mouse and rat brain membranes. In considering possible explanations for the
      differential characteristics of N-methylcarbamylcholine in mouse and rat brain as
      compared to the transfected M1Y1 cells, it was concluded that the difference may
      be attributable to differences in the receptor-transduction coupling efficiency
      and the microenvironment of the muscarinic receptors.

PMID- 7824558
TI  - Pharmacology of ethanol and glutamate antagonists on rodent sleep: a comparative
      study.
AB  - Twenty-five Sprague-Dawley rats were implanted with electrodes for standard sleep
      wake cycle recordings. A guide cannula was stereotaxically implanted into the
      lateral ventricle. Rats were divided into five groups (n = 5) and challenged with
      an intraventricular administration of 10 microliters of a 5 nM solution of
      either: ethanol (EtOH), MK-801, AP5 (noncompetitive and competitive NMDA receptor
      antagonists, respectively), CNQX (AMPA receptor antagonist), or saline. Rats were
      recorded polygraphically for the following 4 h. Results showed that, at
      comparable doses, all tested drugs reduced REM sleep. No significant changes were
      detected in slow-wave sleep or wakefulness. This selective effect of
      glutamatergic antagonists suggests that glutamate may be a selective modulator of
      REM sleep. These findings also show that EtOH shares similar pharmacological
      effects on the sleep-wake cycle of the rat. Ultimately, glutamatergic mechanisms
      could contribute to the EtOH-mediated reduction of REM sleep.

PMID- 7824559
TI  - Genetics of alcoholism: simultaneous presentation of a chocolate drink diminishes
      alcohol preference in high drinking HAD rats.
AB  - Through selective crossbreeding of the N/Nih heterogeneous stock of rats, two
      genetic lines of rats have been developed that are categorized by their
      preference for ethyl alcohol as high alcohol drinking (HAD) and low alcohol
      drinking (LAD) animals. Corresponding to other strains of rat bred for alcohol
      selection or rejection, they were subdivided on the basis of their intake of a
      solution of 10% alcohol vs. water. The present experiments were designed to
      determine whether the HAD-1 and LAD-1 lines are similar to the P and NP rats in
      their profile of alcohol consumption. Five successive three-bottle preference
      tests for alcohol drinking in the presence of water were undertaken in both HAD
      (n = 9) and LAD (n = 10) rats as follows: 10% alcohol for 5 days; 3-30%
      concentrations of alcohol increased over 11 days; the maximally preferred
      concentration of alcohol for 5 days; this maximally preferred concentration of
      alcohol plus either chocolate Slender for 5 days, or an aspartame solution for 5
      days. The intake of alcohol of the LAD rats during the 10% test was 0.4 g/kg/day,
      whereas during the 3-30% test, the maximum intake was 1.7 g/kg/day; their
      maximally preferred concentrations ranged between 7% and 9% alcohol. In contrast,
      the intake of 10% alcohol of the HAD rats was 6.5 g/kg/day, whereas during the 3
      30% test the mean daily intake was 6.6 g/kg/day; the maximally preferred
      solutions of the HAD rats ranged between 13 to 20%, with the mean maximum intake
      of 10.57 g/kg/day reached at the 20% concentration.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7824560
TI  - Effects of chronic phenobarbital administration on forgetting functions in
      pigeons.
AB  - The present study examined the effect of chronic phenobarbital administration on
      forgetting functions based on delayed matching-to-sample performance in pigeons.
      The effects of IP injections of 10 and 20 mg/kg administered over five
      consecutive training sessions were compared to each other and a baseline (no
      drug) condition. Percent correct was reduced as a function of both increasing
      delay and dose of phenobarbital. A quantitative analysis using a negative
      exponential function fitted to bias-free measures of discriminability
      demonstrated that impaired performance following administration of phenobarbital
      was reflected in both an increase in the rate of forgetting as well as a decrease
      in initial discriminability. Furthermore, the influence of proactive interference
      arising from stimuli on previous trials was attenuated at the highest dose level
      (20 mg/kg). Thus, chronic phenobarbital administration impairs memorial function
      and limits the influence of information gained from previous trials on subsequent
      performance. The current effects of chronic phenobarbital administration are
      consistent with the effects of acute administration on forgetting functions
      reported in prior studies.

PMID- 7824561
TI  - PD135158, a CCK-B antagonist, reduces "state," but not "trait" anxiety in mice.
AB  - It has recently been proposed that Balb/c neophobic responses in a free
      exploratory paradigm are related to "trait" anxiety, while the behavior of mice
      in the light/dark choice test paradigm is related to "state" anxiety. The purpose
      of this study was to assess the action of the CCK-B receptor antagonist PD135158
      in both models. Results show that PD135158 was effective in the light/dark choice
      test but not on the Balb/c neophobic reactions in the free exploratory situation.
      It is suggested that PD135158 is specially effective in state anxiety induced by
      fear provoking situations.

PMID- 7824562
TI  - Repeated scopolamine injections sensitize rats to pilocarpine-induced vacuous jaw
      movements and enhance striatal muscarinic receptor binding.
AB  - This experiment was conducted to determine if repeated administration of the
      muscarinic antagonist scopolamine could increase pilocarpine-induced vacuous jaw
      movements and also enhance muscarinic receptor binding. Rats received daily
      injections of either scopolamine (0.5 mg/kg IP) or saline for 14 days. On day 15
      rats received no injections of scopolamine, but did receive injections of
      pilocarpine (1.0, 2.0 or 4.0 mg/kg IP) or saline. After administration of
      pilocarpine or saline, all rats were observed for vacuous jaw movements and
      rearing behavior. The day after pilocarpine injections, rats were sacrificed and
      samples of tissue from the lateral neostriatum were removed to assess muscarinic
      receptor binding using 3H-QNB as the ligand. Analyses of the vacuous jaw movement
      data indicated that there was a significant dose-related increase in vacuous jaw
      movements induced by pilocarpine, and also that there was a significant
      enhancement of pilocarpine-induced vacuous jaw movements in rats pretreated with
      repeated scopolamine injections. There was not a significant scopolamine x
      pilocarpine interaction, suggesting that pretreatment with scopolamine produced
      an apparent parallel shift in the pilocarpine dose-response curve. Pilocarpine
      significantly suppressed rearing behavior, and scopolamine pretreatment
      significantly enhanced the suppression of rearing produced by pilocarpine.
      Analysis of the receptor binding data indicated that there was a significant
      increase in the number of muscarinic receptor sites (Bmax) in rats that received
      repeated scopolamine injections as compared to saline-treated rats.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7824563
TI  - Humans under showers: thermal sensitivity, thermoneutral sensations, and comfort
      estimates.
AB  - Thirty male subjects participated in four experiments under showers to explore
      the sensitivities to water temperature and to its slow or rapid fluctuations.
      After having set the water temperature, at constant flow rate, at either a
      thermoneutral or a preferred level, subjects were asked to detect thermal changes
      or to report their thermosensory and affective judgments associated with water
      temperature changes. Results of water temperature, skin temperature, and
      subjective estimates showed that skin temperature for thermally neutral sensation
      under a shower were very similar to those observed in air, and such a
      thermoneutral level produced no discomfort. Preferred water temperature was
      slightly warmer and led to slightly elevated skin temperatures, warmth, and
      pleasantness estimates. Skin sensitivity to water thermal changes was very acute
      during slow and even more acute during rapid thermal transients. The conclusions
      of the present study are of value in the production of appropriate equipment to
      provide thermal comfort to people taking showers.

PMID- 7824564
TI  - Lack of NPY-induced feeding in cobalt protoporphyrin-treated rats is a
      postreceptor defect.
AB  - The administration of cobalt protoporphyrin results in transient decreases in
      food intake and prolonged weight loss in rats. After IVC injection of cobalt
      protoporphyrin, the food intake of treated rats falls to 10% of vehicle-treated
      control rats within 48 h. At the same time, the concentrations of mRNA for
      neuropeptide Y increase approximately twofold in the hypothalamus. The failure of
      these animals to display a feedings response to elevation of endogenous NPY
      concentration is mimicked by their failure to respond to exogenous. ICV
      injections of neuropeptide Y. Because NPY binding studies are confounded by high
      nonspecific binding, radiolabeled PYY was used to measure binding to hypothalamic
      membranes and for autoradiography with hypothalamic sections. No abnormalities in
      the number of receptors or the affinity of the binding interaction were noted. In
      addition, hypothalamic concentrations of cyclic AMP were unchanged following
      treatment with either cobalt protoporphyrin or NPY. These results indicate that
      the locus of the failure of CoPP-treated animals to feed after administration of
      NPY must be either distal to, or unrelated to, the NPY receptor in the
      hypothalamus.

PMID- 7824565
TI  - Behavioral and neurochemical changes induced by aging in dopaminergic systems of
      male and female rats.
AB  - Changes induced by aging in dopaminergic activity of male and female rats were
      compared by behavioral and neurochemical methods. Young (3 months) and old (23
      months) rats were used. Aging decreased animal activity in the open field and
      increased apomorphine-induced stereotyped behavior. No differences in open field
      data were observed between males and females. Young and aged female rats had
      higher striatal DA and HVA levels than males; aging induced a decrease in both
      striatal DA and HVA levels in males, but not in females. No changes in HVA/DA
      ratios were observed among the different groups. These results show that aging
      reduces nigrostriatal activity as well as nigrostriatal DA levels. Furthermore,
      they indicate that time course events related to aging differ between males and
      females.

PMID- 7824566
TI  - Sensory irritation and coolness produced by menthol: evidence for selective
      desensitization of irritation.
AB  - The temporal characteristics of the oral perception of menthol solutions were
      explored in two experiments. In Experiment 1, 10 samples of either 0.03% or 0.30%
      menthol were presented at 1 min intervals and rated for the perceived intensity
      of cooling and irritation. Reports of sensation quality (burning, tingling,
      stinging and numbing) and pain were also collected. At the higher concentration,
      a significant decrease in perceived intensity was observed over time for
      irritation, but not for cooling. Experiment 2 was designed to explore further the
      nature of the decline in irritation observed in Experiment 1. Employing 1-min and
      5-min inter-stimulus intervals between solutions, it was found that the decrease
      in menthol irritation more closely resembled desensitization than adaptation.
      Decreases in the frequency of reports of the burning and stinging qualities, but
      not the tingling, numbing or cooling qualities, suggested that menthol has a
      specific desensitizing effect on a population of mucosal nociceptive fibers.

PMID- 7824567
TI  - Reduction in food and water intake induced by microinjection of interleukin-1
      beta in the ventromedial hypothalamus of the rat.
AB  - Interleukin-1 (IL-1) is a cytokine which is released during immune activation and
      mediates some of the host's responses to infection and inflammation. Increasing
      evidence suggests that it also has a role as an intrinsic neuromodulator in the
      central nervous system. We report here that microinjections of 5 and 30 ng (286
      fmol and 1.71 pmol) of recombinant human IL-1 beta in the ventromedial nucleus of
      the hypothalamus (VMH) of adult male rats time- and dose-dependently induce
      anorexia and weight loss in two experimental paradigms: rats allowed free-access
      to food and water and food-restricted rats trained to press a lever for food on a
      fixed ratio 10 schedule. IL-1 beta (5 ng) diminished food and water consumption
      by 45 and 30%, respectively, and decreased body weight for at least 24 h
      postinjection in rats fed ad lib. These effects were more severe and lasted at
      least 48 h after infusion of the larger dose of 30 ng. The IL-1 beta-induced
      anorexia and weight loss were neither as large nor as long-lasting in food
      restricted rats. Operant responding for food was decreased 2-4 h postinfusion of
      5 ng IL-1 beta and 2-8 h after 30 ng IL-1 beta, but in both cases returned to
      baseline within 24 h. Body weight was decreased compared to saline injections
      from 4 to 24 h postinfusion. Nevertheless, when allowed to eat ad lib for the 24
      h immediately following the behavioral testing, body weight returned to control
      (5 ng) or near control levels (30 ng).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7824568
TI  - Devazepide alters meal patterns in lean, but not obese, male Zucker rats.
AB  - Meal patterns were recorded for 10.5 h in six lean and eight obese adult male
      Zucker rats after treatment with the cholecystokinin type A (CCKA) receptor
      antagonist, devazepide (750 micrograms/kg, IP, at 1330 h) or vehicle. In lean
      rats, devazepide significantly increased total food intake by 11%, average meal
      size by 35%, and meal duration by 49%. Devazepide also significantly decreased
      the average number of meals by 18%, although this was a smaller effect.
      Devazepide had none of these effects in obese rats. Devazepide treatment altered
      the meal pattern of lean rats so that it was similar to that of obese rats. These
      results demonstrate that endogenous CCK has a satiating effect in lean, but not
      in obese, male Zucker rats, which is the first demonstration of a loss of a
      physiological satiety signal in the obese Zucker rat. This defect could be due
      to: 1) a decrease in the release of endogenous CCK, 2) a decrease in the rate of
      CCK synthesis, or 3) the production of an abnormal form of CCK.

PMID- 7824569
TI  - Effects of environmental enrichment on aggressive behavior, dominance
      hierarchies, and endocrine states in male DBA/2J mice.
AB  - Adult male mice (DBA/2J) siblings were housed three per cage for 6 wk, either in
      standard cages (SC) or in enriched cages (EC). Both attacks among group members
      and attacks against strange intruders were monitored once a week within each of
      22 experimental groups. According to its attacking behavior, each mouse was
      categorized into one of three dominance categories: dominant, subdominant active,
      subdominant passive. Aggressive behavior and social organization were compared
      between the two types of housing conditions, and the effects of housing condition
      and dominance category on endocrinological and some organometrical parameters
      were analysed. The main findings were: (a) Mice in EC attacked intruders
      significantly more frequently compared to mice in SC; (b) In EC groups the
      position of the dominant male was less stable than in SC groups; (c) Plasma
      corticosterone titers (PCT) were significantly elevated in EC. Activities of
      tyrosinehydroxylase (TH) and phenylethanolamine-N-methyltransferase (PNMT) did
      not differ significantly between the housing conditions; (d) TH and PNMT activity
      were significantly enhanced in the dominant males of SC groups compared to
      subdominant passive males. Intermediate activities for both enzymes were
      determined for subdominant active males; and (e) PCT were significantly elevated
      in dominant males of the EC groups compared to subdominant active and subdominant
      passive males and also compared to the dominant males in the SC groups. Findings
      suggest that keeping adult male mice in structured cages can result in increased
      aggression towards intruders, a change in the social organization, and altered
      endocrine states, depending on the individual dominance position.

PMID- 7824570
TI  - Antioxidant enzyme activities in the lymphoid organs and muscles of rats fed
      fatty acids-rich diets subjected to prolonged physical exercise-training.
AB  - Rats weighing 45-50 g were fed 3 diets for 8 wk: a balanced control diet (CD)
      consisting of 4% fat (polyunsaturated/saturated fatty acids [P/S] ratio 2.9/1)
      and two fat-rich diets: polyunsaturated (UD)--P/S 7.6/1 and saturated (SD) P/S
      0.3/1. After 8 wk feeding on the respective diets, rats were subjected to
      swimming for 90 min at 30 degrees C daily, 5 d/wk for 8 wk. At the end of this
      period, the rats were killed and the lymphoid organs (LO--thymus, spleen, and
      mesenteric lymph nodes) and muscles (soleus and gastrocnemius) removed for the
      measurement of TBARs (Thiobarbituric Acid Reactant Substances) content and of the
      activities of antioxidant enzymes (CuZn- and Mn-Superoxide dismutase--SOD--,
      catalase, and glutathione peroxidase). To evaluate the changes in the sites of
      generation of reducing equivalents involved in the formation of free radicals,
      the activities of citrate synthase and glucose-6-phosphate dehydrogenase were
      measured. The exercise-training clearly modified the enzyme activities and TBARs
      content of the lymphoid organs and skeletal muscles, but this effect was
      dependent upon the diet given to the rats. However, fatty acid rich diets had
      presented a more pronounced effect on the studied aspects than did physical
      activity. Although one could expect a summatory effect of polyunsaturated fatty
      acid-rich diet and exercise-training, swimming increased the activities of CuZn-
      and Mn-SOD in almost all tissues from the elevated level promoted by fat-rich
      diets.

PMID- 7824571
TI  - Pelvic neurectomy blocks oxytocin-facilitated sexual receptivity in rats.
AB  - The effect of bilateral pelvic, hypogastric, or pudendal neurectomy on oxytocin
      induced facilitation of lordosis behavior was examined in ovariectomized,
      estrogen, and progesterone primed female rats. Oxytocin-induced facilitation of
      lordosis behavior was significantly decreased following bilateral pelvic, or
      combined bilateral pelvic and hypogastric neurectomy. Hypogastric only or
      pudendal only neurectomy had no effect on the facilitation of lordosis behavior
      after systemic administration of oxytocin. These results suggest that the
      integrity of the pelvic nerve is necessary and sufficient to mediate the
      stimulatory effects of systemically administered oxytocin on receptivity.

PMID- 7824572
TI  - Lysine deficient diet and lysine replacement affect food directed operant
      behavior.
AB  - As a test for specific hunger for amino acids with the goal of identifying brain
      regions which might mediate motivation to alleviate L-lysine (Lys) deficiency,
      rats were trained to lever press to receive complete diet. Rats were given Lys
      deficient (Lys-def) diet ad lib. Intraperitoneal (IP) injection of Lys, 2 h
      before the test session, inhibited lever pressing. Lys injected animals pressed
      at nearly the same low rate as did animals fed ad lib complete diet, although the
      response of saline injected animals was also partially decreased. Next, osmotic
      minipumps were implanted IP and animals given Lys-def diet ad lib. Chronic Lys
      infusion also strongly inhibited lever pressing. Rats allowed ad lib access to
      Lys to drink drank significantly more Lys than when given complete diet. Lys
      chronically infused by minipump into the lateral hypothalamus, also inhibited
      pressing by rats given Lys-def diet. Therefore, animals lacking Lys in the diet
      will work to receive complete diet, but replacement of Lys by drinking, chronic
      IP infusion, or directly into the lateral hypothalamic area inhibits bar pressing
      behavior.

PMID- 7824573
TI  - MBR: a computer program to record and analyze parental behavior in rodents.
AB  - The Maternal Behavior Recorder (MBR) is a microcomputer program designed to
      record and analyze data from research on parental behavior of rats and other
      rodents. It is used to record the specific, characteristic patterns of maternal
      care in rodents: nest building, grooming, licking, crouching, and retrieval of
      pups. Moreover, it analyzes these events in terms of frequency and duration,
      allowing any events erroneously recorded to be corrected. The MBR can also
      simultaneously control observations made by one or two experimenters, and it
      calculates a set of reliability measures between them.

PMID- 7824574
TI  - Inescapable shock induces the opposite changes of the plus-maze test behavior in
      rats with divergent coping strategy.
AB  - Behavior in the elevated plus-maze and plasma corticosterone levels were
      investigated in Koltushi high-avoidance (KHA) and low-avoidance (KLA) rat strains
      subjected to inescapable shock (IS) or daily handling for 10 days. These strains
      have been genetically selected on the basis of divergent acquisition of a
      conditioned avoidance response in a two-way shuttle-box. Naive KHA rats were more
      anxious than KLA ones. Following exposure to IS, the time spent in open arms was
      increased in KHA rats but decreased in KLA rats. After handling, the time spent
      in open arms increased only in KHA rats and became similar in both strains. There
      were no differences in plasma corticosterone levels between naive animals.
      Exposure to either IS or handling increased the plasma corticosterone levels in
      KLA rats. In KHA rats, handling reduced the plasma corticosterone levels, and
      exposure to IS had no effect. The present results suggest that the stress-induced
      changes in anxiety levels depend on the coping strategy of the subject.

PMID- 7824575
TI  - Effects of bilateral basomedial hypothalamic lesions on feeding, fattiness, and
      reproductive functions in the White Leghorn hen.
AB  - During the last three decades, syndromes caused by bilateral destruction of the
      basomedial hypothalamus (BMH) were extensively studied in cockerels but not in
      hens. In the present study bilateral electrolytic lesions in the BMH of White
      Leghorn (WL) hens produced two main sets of symptoms: (a) Obese, functionally
      castrated hen (OFC); and (b) Obese, laying hen (OL). Following the placement of
      the hypothalamic lesion, the OFC hens developed transient hyperphagia, that was
      followed by hypophagia. Weight gain was accelerated in both periods, and marked
      obesity developed. These hens had high hematocrit values, and atrophied ovary,
      oviduct, comb, and adenohypophysis. Plasma estrogen, and total lipids and liver
      weight were reduced in the OFC hens. In these hens, the lesioned area included
      the ventromedial hypothalamic nucleus (VMH), the mammillary nuclei, and in some
      birds also the arcuate nuclei, and the tuberal nucleus. The OL hens manifested
      transient hyperphagia that subsided into normophagia with the development of
      obesity. These hens were less obese than the OFC ones and showed normal
      reproductive traits. The lesioned area in the OL hens was limited to the VMH.
      Unlike functionally castrated cockerels, where the induced fattiness is
      accompanied with higher rate of lipogenesis, the OFC hen manifested a unique
      syndrome: increased fattiness with arrest in estrogen-dependent lipogenesis.

PMID- 7824576
TI  - Cholecystokinin loses its satiating property in food deprived rats.
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 mol.l-1 sucrose was injected into
      the mouth every 5 min during 65 min. Five minutes after the beginning of the
      session, 2 micrograms.kg-1 cholecystokinin (CCK) were injected IP Typical
      ingestive facial consummatory responses were observed in response to sweet
      stimuli before IP CCK. Aversive consummatory responses were observed in response
      to sweet stimuli after the IP CCK (negative alliesthesia). In the second part of
      the experiment the rats were denied access to food for 36 h and their mean body
      weight decreased from 426 g to 395 g. When the food deprived rats were subjected
      again to the same gustatory sessions, the IP CCK was not followed by negative
      alliesthesia in response to sweet stimuli. After recovery of initial body weights
      CCK was followed again by a strong negative alliesthesia. These results in rats
      show that the CCK mediation of duodenal satiety was hindered by body weight
      decrease.

PMID- 7824577
TI  - Superoxide dismutase, catalase, and glutathione peroxidase activities in muscle
      and lymphoid organs of sedentary and exercise-trained rats.
AB  - The effect of swimming-training upon the activities of the enzymes involved in
      the generation of reducing-equivalents (citrate synthase-mitochondria and glucose
      6-phosphate dehydrogenase-cytosol) and of antioxidant enzymes (CuZn- and Mn-SOD,
      catalase and glutathione peroxidase) in the lymphoid organs (thymus, mesenteric
      lymph nodes and spleen) was examined. The skeletal muscles (soleus-red and
      gastrocnemius-white) were also studied. Although our data suggest an apparently
      random, organ-specific change in enzymatic activity, some interesting trends can
      be observed. Firstly, the increased citrate synthase and Mn-SOD activities
      observed in red, but not in white muscle, corroborate the well-known effect of
      endurance exercise-training on mitochondrial oxidative metabolism. Secondly,
      there was an inverse relationship between TBARs-monitored lipoperoxidation and
      glutathione peroxidase activity in all tissues studied, what is in accordance
      with the previous findings showing that such enzyme exerts the fine control of
      intracellular lipoperoxide concentration. Except in the case of the spleen, there
      was a trend for elevated glucose-6-phosphate dehydrogenase activity, coadjuvant
      of glutathione peroxidase in the antioxidant response to physical exercise in all
      tissues. Thirdly, Mn-SOD and catalase were conspicuously associated to oxidative
      stress in the thymus, while glutathione and catalase could be linked to this
      parameter in the spleen. Fourthly, the lymph nodes seem to be more dependent on
      the glucose-6-phosphate dehydrogenase/glutathione peroxidase pair for protection
      against damage promoted by physical exercise. Mn-SOD and catalase activities were
      lower in the lymph nodes after swimming training.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7824578
TI  - Comparison of peripheral blood flow patterns associated with the defense reaction
      and the vigilance reaction in rabbits.
AB  - The present study compared the skeletal muscle and visceral blood flow patterns
      elicited by electrical stimulation of the hypothalamic defense area (HDA) and the
      hypothalamic vigilance area (HVA) of the rabbit. Electrical stimulation of the
      HDA evoked a pressor response, tachycardia, hyperventilation, an increase in
      blood flow to the skeletal muscles and decreased blood flow to visceral organs.
      Stimulation of the HVA yielded a pressor response, bradycardia, inspiratory apnea
      and decreased blood flow to both the skeletal muscles and the viscera.
      Intravenous injections of atropine methyl nitrate significantly reduced the HVA
      elicited bradycardia and the HDA-elicited increase in blood flow to the skeletal
      muscles, thereby providing evidence that the bradycardia was mediated by vagal
      efferents and that the rabbit has an atropine-sensitive cholinergic vasodilation
      system. The decrease of blood flow to the visceral organs associated with the
      defense reaction and vigilance reaction was reversed by intravenous injections of
      the alpha-1 receptor blocker prazosin.

PMID- 7824579
TI  - Anabolic-androgenic steroids and aggression in castrated male rats.
AB  - The resident-intruder paradigm of aggression was utilized to evaluate the
      aggression-inducing properties of two anabolic-androgenic steroid (AAS)
      compounds, methyltestosterone and stanozolol, in castrated male rats. Three
      weekly tests were conducted. On test week three, castrated males treated with
      methyltestosterone displayed levels of aggression equivalent to the levels
      displayed by castrated males treated with testosterone propionate on most of the
      behavioral indices assessed. In contrast, treatment with stanozolol at the dose
      used in this study was completely ineffective in eliciting aggressive behavior.
      AAS effects on aggression were mirrored by their ability to stimulate seminal
      vesicle growth. There were no effects of AAS treatments on the levels of
      locomotor activity. These findings highlight the heterogeneity of AAS effects on
      the nervous system and behavior and indicate that the psychological effects
      reported by human AAS abusers may depend upon the distinct chemical structures of
      the abused steroids.

PMID- 7824580
TI  - Conditioned place preference in female hamsters following aggressive or sexual
      encounters.
AB  - Prior studies have demonstrated the utility of conditioned place preference
      procedures for examining the motivational or rewarding properties of behavior.
      The purpose of this experiment was to assess whether female Syrian hamsters would
      show evidence of conditioned place preference for aggression or sexual behaviors.
      Weekly conditioning sessions were conducted for three groups of female hamsters
      for 5 weeks. One group of female hamsters engaged in sexual activity with a male
      hamster in the gray compartment of a place preference apparatus. A second group
      of females experienced aggressive interactions with a male when placed together
      also in the gray compartment. Females in each of these conditioning groups were
      placed alone in the white compartment within 1 h of the behavioral interactions.
      A control group of hormone-treated females was placed alone in both compartments
      of the apparatus. Following the conditioning sessions, all females were given
      free access to the conditioning apparatus. Females with prior sexual or
      aggressive experience spent significantly more time in the gray compartment than
      they did before conditioning. Control females did not show any significant change
      in their preference for either compartment of the apparatus. The results suggest
      that female hamsters prefer an environment associated with the prior rewarding
      properties of sexual or aggressive interactions.

PMID- 7824581
TI  - Effects of hormonal treatment and history on scopolamine inhibition of lordosis.
AB  - The muscarinic receptor blocker, scopolamine, inhibits the display of lordosis
      behavior in female rats but its effectiveness depends on hormonal conditions. In
      these experiments, systemic administration of scopolamine (0.031-4 mg/kg)
      inhibited lordosis in ovariectomized rats brought into receptivity by treatment
      with a low dose of estradiol benzoate (EB, 0.25 micrograms for 3 days) with
      progesterone (P, 500 micrograms for 1 day), or a high dose of EB (25 micrograms
      for 3 days) with and without P. However, the effectiveness of scopolamine was
      reduced at the high dose of EB and with the addition of P. Furthermore,
      scopolamine failed to inhibit lordosis in females treated on a second week with
      the high dose of EB with or without P, unless an interval of at least 3 weeks
      separated the two sets of steroid treatments. The reduced effectiveness of
      scopolamine cannot be explained by peripheral mechanisms because its inhibitory
      effect on lordosis also was reduced following repeated hormonal exposure even
      when scopolamine was infused directly into the lateral ventricles.

PMID- 7824582
TI  - Agonistic behavior, plasma stress hormones, and metabolites in response to dyadic
      encounters in domestic pigs: interrelationships and effect of dominance status.
AB  - Agonistic behavior, neuroendocrine, and plasma metabolite changes were studied in
      16 domestic Large White pigs (100 +/- 5 kg) submitted to dyadic encounters (30
      min) in a neutral environment. The animals had been housed individually for 2
      months prior to the experiment. Aggressive and submissive behaviors were recorded
      for each animal during the encounter. Surgically implanted catheters allowed
      collection of blood samples at selected times. Plasma levels of cortisol,
      catecholamines, and metabolites were determined and compared with data obtained
      on eight control pigs kept under resting conditions. Resting plasma cortisol
      levels tended to be higher in subordinate compared to dominant subjects,
      suggesting a relationship between baseline adrenocortical activity and submissive
      behavior during aggressive encounters in domestic pigs. Plasma norepinephrine and
      epinephrine levels did not differ between dominants and subordinates, but they
      were linearly correlated with aggressive behaviors. Metabolic state changed in
      response to the encounters, as evidenced by increased plasma levels of free fatty
      acids, glucose, and lactate at the end of the dyads. Dominance status did not
      significantly affect plasma metabolite levels. Plasma lactate and glucose levels
      were linearly correlated with both aggressive behaviors and plasma
      catecholamines. The present results provide evidence suggesting that stimulation
      of the sympathetic nervous system and physical activity are both involved in the
      control of the mobilization of body energy sources in response to aggressive
      encounters in domestic pigs.

PMID- 7824583
TI  - Sensitivity to foot shock in autoimmune NZB x NZW F1 hybrid mice.
AB  - Prior studies have demonstrated deficits in active avoidance learning in young
      (12-week-old) mice that develop lupus-like autoimmunity. Because foot shock is
      the motivating stimulus in this task, sensitivity to foot shock was assessed in
      autoimmune NZB x NZW F1 hybrid (B/W) and nonautoimmune NZW female mice. Responses
      to shock at levels ranging from 0.05 to 1.6 mA were recorded twice during the
      development of autoimmunity. At 12 weeks of age, B/W mice did not differ from NZW
      mice in sensitivity to shock. However, at 24 weeks of age, when antibody levels
      were elevated, sensitivity to foot shock decreased in B/W mice at low shock
      levels and increased at high shock levels. A neurological battery revealed no
      deficits that could account for these effects. However, IgM anti-DNA antibody
      levels were positively correlated with responsiveness to high levels of shock.
      The change in the pattern of sensitivity at 24 weeks may be due to a combination
      of disease-related sensory impairment at low shock levels and hyperalgesia at
      high shock levels. The response to high levels of shock may also be an indication
      of enhanced emotionality, an interpretation consistent with reports in other
      lupus-prone strains and affective disorders in humans with lupus.

PMID- 7824584
TI  - The breathing bear: effects on respiration in premature infants.
AB  - The sleep states and the regularity of quiet sleep (QS) respiration were
      investigated in premature infants who were provided a "breathing" teddy bear. The
      bear (BrBr) is a source of optional rhythmic stimulation that reflects the
      breathing rate of the individual infant it is with. At 33 weeks CA, 19 premature
      infants were given a BrBr and 17 were given a nonbreathing bear (N-BrBr). At 35
      weeks CA, and again at 45 weeks CA, a 1-2-h interfeed motility recording was
      obtained. These analog signals were scored for active sleep, QS, and wakefulness;
      and each 10-s epoch of QS was judged for regularity of respiration using a four
      point rating scale. At 35 weeks, the BrBr babies showed slower and more regular
      respiration during QS. At 45 weeks, the BrBr babies showed more QS and less
      active sleep. At both ages, only the BrBr babies showed a correlation between
      respiratory regulatory and the amount of QS. The findings suggest facilitation of
      neurobehavioral development as well as entrainment from optional stimulation,
      which reflects one of the infant's own biological rhythms.

PMID- 7824585
TI  - Effects of chronic mild stress on performance in behavioural tests relevant to
      anxiety and depression.
AB  - Chronic exposure to mild unpredictable stress (CMS) has previously been found to
      depress the consumption of a weak (1%) sucrose solution by rats. This effect was
      confirmed in each of three experiments in the present study, following which
      behaviour was examined in other tests relevant to either depression or anxiety.
      CMS did not significantly affect behaviour in the social interaction test and
      caused an anxiolytic-like profile in the elevated plus-maze. CMS increased
      submissive behaviour in the resident-intruder test, and decreased male sexual
      behaviour. The latter effect was more pronounced in animals reared in isolation
      from the time of weaning; isolation rearing did not influence sexual behaviour in
      nonstressed animals. Isolation rearing also potentiated the effect of CMS on
      sucrose drinking, in both male and female rats. These results support the
      relevance of the CMS procedure as a potential animal model of depression.

PMID- 7824586
TI  - Validity of a delayed conditional discrimination task as a model for working
      memory in the rat.
AB  - A delayed conditional discrimination (DCD) task in the rat was modified by
      requiring a response on an admission lever at the end of each delay. This
      requirement proved effective in precluding the use of positional cues as
      mediating behavior. Furthermore, validity of the procedure was assessed by
      examining how performance changed as a result of: length of the delay,
      retroactive and proactive interference, and encoding time. Results showed that
      log d, a measure of stimulus discriminability, decreased on longer delays
      (Experiment 1); decreased when an interfering stimulus was presented during
      delays (Experiment 2); decreased when the intertrial interval was made shorter
      (Experiment 3); and decreased when the sample stimuli were presented for a
      shorter period of time (Experiment 4). Log b, an index of bias, remained low
      throughout the study, indicating that no significant response bias was present.
      Taken together, the results support the notion that this modified DCD task is a
      valid model for working memory that effectively precludes the use of positional
      cues as mediating behavior in the rat.

PMID- 7824587
TI  - Conditioning of brain stimulation-induced presleep behavior.
AB  - Experiments were conducted on three chronic unanesthetized, undrugged cats.
      Electrical stimulation of the basal forebrain area (BFA) resulted in presleep
      behavior (i.e., the cats would sit or lie down, and EEG spindles would arise).
      After several sessions (conducted twice a week), two of these cats began to
      exhibit presleep behavior almost immediately after entering the experimental
      compartment, even before the application of BFA stimulation. The third cat often
      ate some food (which was always present in the compartment) before showing
      presleep behavior. When stimulation was withheld during an extinction procedure,
      the cats still exhibited presleep behavior in the absence of stimulation during
      several sessions. We conclude that repeated BFA stimulation led to conditioning
      of the stimulation effects, that is, the presleep behavior that was evoked by the
      environmental situation alone, without BFA stimulation or any other intermittent
      stimulus.

PMID- 7824588
TI  - Attenuation of the expression of circadian rhythms by chronic outputs from the
      VMH in rats.
AB  - To alter neural networks in a restricted area of the brain, we previously
      developed the hydro-polymer gel (PG) implantation technique. In this study, we
      found that bilateral or unilateral injection of PG (1.6 microliters) into the
      ventromedial nucleus of the hypothalamus (VMH), contrary to injections into the
      preoptic area (POA) or posterior hypothalamic area (PHA), severely attenuated
      circadian changes of locomotor activity in blinded female rats. In addition, PG
      injection into the VMH also suppressed circadian changes in serum melatonin
      levels and induced persistent estrus. The effect of PG injection into the VMH on
      free-running rhythm was blocked by a complete cut around the VMH or a dorsal cut
      of the VMH but not by anterior or posterior cuts of the VMH. These results
      suggest that PG injection into the VMH induces some form of neural output via a
      dorsal route of the VMH that affects the generation of circadian activity rhythm.

PMID- 7824589
TI  - Maternal influences on milk intake in SHR and WKY pups.
AB  - Mother to pup milk transfer was examined in the spontaneously hypertensive rat
      (SHR) and its normotensive progenitor, the Wistar-Kyoto (WKY). Litters of SHR and
      WKY pups were either reared by their natural mothers or cross-fostered to mothers
      of the opposite strain shortly after birth. At postpartum days 7 and 14, pup body
      weights were monitored throughout a 2-h maternal separation period followed by a
      3-h refeeding period during which pups remained with their mothers. Weight
      increases of pups over the refeeding period served as an indirect measure of milk
      ingestion. At postpartum day 7, both SHR and WKY pups nursed by SHR mothers
      received lower quantities of milk compared to their counterparts nursed by WKY
      mothers. Maternal strain differences in milk transfer were largely attenuated at
      postpartum day 14. The different nutritional environments provided by SHR and WKY
      mothers may mediate the alterations in offspring cardiovascular physiology and
      physical development that occur with reciprocal cross-fostering.

PMID- 7824590
TI  - Transmission of food preference in the rabbit: the means of information transfer.
AB  - Rabbit pups raised by mothers fed different diets during pregnancy and lactation
      show a clear preference for the diet of their mother at weaning. By supplementing
      does' lab chow diet with aromatic juniper berries, the present study aimed to
      investigate the relative importance of 1) fecal pellets deposited by the mother
      in the nest, 2) prenatal experience in utero, and 3) contact with the mother
      during nursing in determining pups' later food preference. The three means of
      transmission were found to be equally effective. Thus, pups from normally fed
      does raised with fecal pellets from juniper-fed mothers, pups from juniper-fed
      mothers cross-fostered to normally fed does immediately after birth, and pups of
      normally fed mothers nursed by juniper-fed does all showed as strong a preference
      for juniper as pups raised by juniper-fed mothers exclusively. Such apparent
      redundancy may not only help insure that less aromatic substances or substances
      transmitted differentially by these routes are learned, but also that pups can
      acquire a preference for a variety of foods eaten by their mother at different
      times.

PMID- 7824591
TI  - Differing mechanisms for proactive effects of intermittent and single shock on
      gastric ulceration.
AB  - Rats exposed to either 80 5-s shocks on a VT 60-s or to a single 400-s shock plus
      80-min rest in the shock apparatus show dramatically increased degree of
      ulceration induced 72 h later by exposure to 75-min restraint-in-water stress (at
      19 degrees C). However, the proactive effect of the 80 shocks on later gastric
      ulceration was blocked by SC injection of 7 mg/kg naltrexone 20 min prior to the
      shock session; naltrexone treatment prior to the single shock session had no
      ameliorating effect. A second experiment confirmed opioid involvement in the
      proactive augmentation of vulnerability by showing that when a 20 mg/kg injection
      of morphine replaced the shocks, rats showed a comparable increase in
      vulnerability. A third experiment replicated the basic findings from the first
      experiments that 80 intermittent shocks increase vulnerability to the
      ulcerogenicity of restraint-in-water and that this effect can be mimicked by
      replacing the shock stress with a 20 mg/kg injection of morphine; however, other
      groups showed that injection of 40 mg/kg produced a similar effect whereas 10
      mg/kg was ineffective as a mimic. This suggests that there are at least two types
      of proactive effects from shock experiences that can increase later vulnerability
      to shock-induced gastric ulceration; one is opioid mediated and the other is not.
      This finding parallels reports made about mediation of prior shock-induced
      hypoalgesias and expands the spectrum to psychosomatic phenomenon.

PMID- 7824592
TI  - Effect on rat feeding behavior of two selective D2 dopamine agonists.
AB  - B-HT 958 and SND 919, two selective agonists at D2 dopamine receptors, were
      examined for their influence on the feeding behavior of fasted rats. When food
      intake was determined in the rat's individual home cage, it was found to be
      reduced by both drugs at low sedative doses during the first hour after treatment
      and by SND 919 at the highest dose (which also elicits stereotypy) only 24 h
      later. However, SND 919 and B-HT 958 had no significant effect on feeding
      evaluated according to the X-maze and tube feeding tests. Analysis of the
      results, seen in the context of other behavioral signs produced by the drugs,
      suggests that data on feeding may vary depending on the experimental model used
      and can be modified by extraneous factors that interfere with a specific effect
      on food intake.

PMID- 7824593
TI  - Brain selenium status and behavioral development in selenium-deficient
      preweanling mice.
AB  - The influence of Se deficiency on behavioral development in preweanling mice was
      evaluated. Female ICR mice were fed either Se-deficient or control diet
      (containing < 20 or 400 ng Se/g diet, respectively) from 4 weeks before
      conception to the end of the suckling period. In the offspring of Se-deficient
      dams, liver and brain Se levels were reduced to < 5% and 60% of those in the
      control offspring, respectively, from as early as the third postnatal day. At
      weaning, brain Se content exceeded the hepatic one in Se-deficient offspring,
      whereas in the control offspring the liver contained 10 times more Se than the
      brain did. Thus, tissue-specific metabolism of Se was already functioning during
      the neonatal period. When placed in a thermogradient and allowed to move along
      the gradient, Se-deficient offspring exhibited a preference for a significantly
      warmer environment than did the controls. They also showed slightly retarded
      development of walking ability. These results showed that Se-deficient offspring
      differed from the controls in behavioral development. Possible mechanisms of
      these alterations are discussed.

PMID- 7824594
TI  - Memory enhancement after drinking ethanol: consolidation, interference, or
      response bias?
AB  - One explanation for memory facilitation is that alcohol has a short-term
      neurochemical stimulating effect on consolidating neural networks when material
      is learned before drinking. Contrary to the consolidation hypothesis, when the
      consolidation interval was manipulated the results showed that the effects of
      alcohol were not time dependent. Compared to placebo subjects, alcohol
      significantly facilitated the recall of 25 words whether administered immediately
      or 40 min after learning. In addition, alcohol significantly increased the memory
      of words associated with pictures when incidentally learned before drinking and
      significantly decreased incidental learning after drinking. Another explanation
      for memory facilitation is that alcohol's depressive physiological effect impairs
      the acquisition of new information, like sleeping after learning, and enhances
      memory by reducing subsequent interference. Consistent with the retroactive
      interference hypothesis, the effects of alcohol reduced interpolated
      interference, were greater on recall than recognition, and were immune to time
      delays. Contemporary theories view memory enhancement attributed to alcohol as
      indirectly influencing response biases and contextual cues associated with
      retrieval from episodic memory.

PMID- 7824595
TI  - Different effects of amphetamine on reinforced variations versus repetitions in
      spontaneously hypertensive rats (SHR).
AB  - The spontaneously hypertensive rat (SHR) may serve as an animal model of human
      attention deficit hyperactivity disorder (ADHD). We compared performances of SHRs
      and Wistar-Kyoto normotensive controls rats (WKY) in two experiments. When
      rewarded for varying sequences of responses across two manipulanda, the SHRs were
      more likely to vary than the WKYs. On the other hand, when rewarded for
      repetitions of a small number of sequences, the WKYs were more likely to learn to
      repeat. Both of these results confirm previous findings. Injecting 0.75 mg/kg d
      amphetamine facilitated learning by SHRs to repeat the required sequences, with
      amphetamine-injected SHRs learning as rapidly as saline-injected, control WKYs.
      On the other hand, amphetamine tended to increase variability in both strains
      when high levels of variations were required for reward, and to decrease it in
      both strains when low levels of variability were required. Thus, amphetamine may
      have different effects on reinforced repetitions vs. reinforced variations.

PMID- 7824596
TI  - Persistent stress-induced sensitization of adrenocortical and startle responses.
AB  - We assessed the functional adrenocortical and behavioral state of rats previously
      exposed to repeated stressor presentations. In Experiment 1, the whole-body
      startle response to threshold (91 dB) and suprathreshold (96 dB) stimuli was
      assessed in rats given 3 daily sessions (3DS) of 40, 2-mA tailshocks. The 3DS
      rats showed an exaggerated startle response to the threshold auditory stimulus 4
      days poststressor compared to nonshocked controls (CON). An exaggerated startle
      response in stressed rats was not evident either 1 day or 10 days poststressor.
      In Experiment 2, adrenocortical sensitization and behavioral reactivity were
      assessed in rats exposed to 1 day (1DS) or 3 days of our stress regimen. Stressed
      rats exhibited elevated basal plasma corticosterone (CORT) levels 1 day
      poststressor which recovered by 9 days poststressor. Stressed rats also exhibited
      suppressed open-field activity 4 days poststressor. On the 10th day poststressor,
      rats were exposed to a single tailshock. The 1DS and 3DS rats showed both a
      sensitized and prolonged CORT response to stressor reexposure compared to control
      rats which received only the single tailshock. In addition, on the 11th day
      poststressor 3DS rats exhibited a moderate recapitulation of the elevated basal
      CORT levels seen after the initial stressor exposures. Thus, exposure to our
      stress regimen produces a chronic stress state in rats characterized by
      persistent behavioral and adrenocortical sensitization, as well as suppressed
      open-field activity and elevated basal CORT levels. Rats exhibiting a chronic
      stress state may be appropriate as a model for the study of stress-related
      psychophysiological illnesses, such as posttraumatic stress disorder.

PMID- 7824597
TI  - Ram sexual pheromone: first approach of chemical identification.
AB  - A series of experiments has been designed with the aim of identifying the
      pheromone of the ram responsible for the primer effect--induction of a LH peak
      and ovulation--in anoestrous ewes. In a first experiment, the pheromonal activity
      of various sources was tested, extract of ram fleece and ante orbital gland
      secretion induced characteristic changes in LH secretion, whereas urine was
      ineffective. A second experimental series showed that an accurate separation of
      the ram's fleece extract in acid and neutral fractions resulted in each case in a
      complete loss of activity whereas both together were efficient, indicating that
      the pheromonal action involves several components. From GC-MS analysis of both
      fractions, and after comparison of male and female wool extract, semi-synthetic
      formulations were tested. The association of synthetic 1,2-hexadecanediol and 1,2
      octadecanediol with the natural acid fraction was efficient in stimulating LH
      release in anoestrous ewes. As the most frequent linear fatty acids have been
      shown not to be necessary, a role of branched and oxygenated fatty acids has been
      hypothesised.

PMID- 7824598
TI  - Sleep-wake variables and EEG power spectra in Mongolian gerbils and Wistar rats.
AB  - Using electroencephalographic methods (EEG), we have analyzed the basal sleep
      structure and the EEG power spectra of gerbils and rats during periods of
      wakefulness (W), synchronized sleep (SS) and paradoxical sleep (PS). During the 6
      hr light period examined, duration of sleep was similar for rats and gerbils, but
      gerbils showed fewer PS episodes and a longer amount of SS episodes followed by
      wakefulness. In addition, SS episodes preceding PS were of longer duration in
      gerbils than in rats. EEG power spectral analysis indicated a higher relative
      output in the 1-4 Hz range in gerbils in comparison with rats. On the whole, the
      data indicate the existence of significant differences in the basal sleep
      structure and EEG power spectra of gerbils and rats. This background information
      might be useful in the comparison of the effects of a given experimental
      treatment, such as cerebral ischemia, on the EEG activity of these two animal
      species.

PMID- 7824599
TI  - Elevated sweet taste pleasantness ratings in bulimia nervosa.
AB  - Recent studies suggest that some patients with bulimia nervosa may experience
      elevated pleasantness responses to sweet taste. This study explored possible
      associations between symptoms patterns and pleasantness ratings for sucrose
      solutions in bulimic patients. Subjects included 15 women meeting DSM III-R
      criteria for narrowly defined bulimia nervosa (no history of other eating
      disorder); five patients with current bulimia nervosa and a past history of
      anorexia nervosa; and 20 healthy age-matched female controls. Subjects ate a
      standardized breakfast prior to the morning study visit. Sucrose-water solutions
      (0% to 40% sucrose) were rated for sweetness intensity and pleasantness. Patients
      with narrowly defined bulimia nervosa showed significantly higher pleasantness
      ratings for 40% sucrose solutions than controls and patients with a history of
      anorexia nervosa. Pleasantness ratings were not significantly correlated with
      frequency of binge eating or purging behaviors. These results extend previous
      evidence for altered sweet taste pleasantness responses in bulimia nervosa, and
      for differences in eating-related behaviors between patients with narrowly
      defined bulimia nervosa vs. those with past anorexia nervosa.

PMID- 7824600
TI  - Cadmium-induced sexual dysfunction does not involve increased hepatic metabolism
      of testosterone nor increased circulating levels of corticosterone.
AB  - Sexually experienced male rats were injected IP with 0, 0.3, 1.5, 3.0, or 6.0
      mg/kg cadmium chloride. The highest dose was fatal within 48 h of injection. A
      dose-related deficit in erectile function was observed in ex copula tests 48 h
      after injection. Copulatory dysfunction was evident in mating tests 72 h after
      injection. Hepatic mixed function oxidase activity after 0.3 mg/kg injections was
      not different from controls, but was diminished by 50% in rats treated with 3.0
      mg/kg. The higher cadmium doses (1.5 and 3.0 mg/kg) were associated with
      equivalent and marked reductions in circulating testosterone levels, and lesser
      decrements in circulating corticosterone levels. The rats treated with 1.5 or 3.0
      mg/kg cadmium chloride lost weight (32 +/- 12 and 39 +/- 9 g, respectively).
      Relative decapsulated adrenal gland weights were markedly increased in rats
      treated with 3.0 mg/kg. These data indicate that exposure to cadmium is
      associated with alterations in sexual, hepatic, and adrenal function, with
      erectile dysfunction occurring at the lowest dose. The effects on copulatory
      behavior are especially striking because it requires some weeks for copulatory
      behavior to wane following castration.

PMID- 7824601
TI  - Insulin increases the daily food intake of diabetic rats on high and low fat
      diets.
AB  - The effects of insulin dose and diet composition on daily food intake were
      investigated by IV infusion of insulin in doses of 2 to 5 U/day into diabetic
      rats consuming either a high CHO or high fat diet. The daily food intake of the
      diabetic rats on both diets increased significantly over baseline levels (p <
      .01) at the low insulin doses and was maintained at these elevated levels through
      the 5 U/day dose. Insulin increased the rate of weight gain from Ig/day during
      baseline to 2 and 2.5 g/day in high CHO and high fat fed diabetics (p < .01).
      These results show that treatment of diabetic rats with continuous low doses of
      IV insulin results in a 40% increase in daily food intake regardless of the diet
      consumed and this increase is accompanied by an increase in rate of body weight
      gain. While the high fat fed diabetics were relatively hypoglycemic, these
      increases in intake are not the result of insulin-induced hypoglycemia, since
      blood glucose concentrations are significantly elevated when the increases occur
      at the lower insulin doses (p < .01). Thus, peripheralinsulin infused at
      physiological levels stimulates rather than inhibits daily food intake.

PMID- 7824602
TI  - Hepatic portal and vena cava insulin infusion increase food intake in diabetic
      rats.
AB  - To test whether the route of insulin delivery has a major effect on the increase
      in daily food intake associated with chronic insulin treatment, insulin was
      continuously infused into either the vena cava (VC) or the hepatic portal (HP)
      vein of 23 diabetic Lewis rats. Increasing insulin doses in both the VC (2 to 6
      U/day) and HP (1.5 to 3.5 U/day) groups significantly increased daily food intake
      (p < .05). Intake was higher in the VC group at 3 U/day but not at 2U/day. When
      insulin was delivered at a low fixed dose, daily food intake of both the VC and
      HP groups only increased after urinary glucose losses increased. The rate of
      weight gain increased significantly in the VC varied group (p < .05). Insulin
      administration also increased energy expenditure (p < .01). These results suggest
      that the extent of the increase in daily food intake and body weight that occurs
      with peripheral exogenous insulin administration is dependent on the route of
      infusion.

PMID- 7824603
TI  - Rotation fasciocutaneous flap repair of lower limb defects.
AB  - The rotation design was applied to fasciocutaneous flap repair of lower limb
      defects to produce a functional and aesthetic result superior to that obtained by
      the transposition design. A prospective, consecutive series of 21 patients is
      reported, 14 males and 7 females, ranging in age from 17 to 81 years (mean 43
      years). The primary defects, 8 traumatic, 12 cutaneous malignancy excisions, and
      1 radionecrotic ulcer, ranged in size from 3.5 x 3 cm to 10 x 8 cm (mean 6.6 x 5
      cm). The rotation fasciocutaneous flap base ranged from 5 to 25 cm (mean 12 cm),
      and the radius ranged from 4.5 to 20 cm (mean 9 cm). The inclusion of a back-cut
      at the flap base permitted direct donor-site closure in all but one patient,
      obviating the need for a split-thickness skin graft and avoiding the otherwise
      inevitable significant contour defect. Postoperative bed rest ranged from 3 to 7
      days (mean 5 days). Three minor and no major complications occurred, and there
      was complete survival of all flaps. The results in this series indicate a role
      for the rotation fasciocutaneous flap in the management of traumatic and
      excisional defects in the lower limb. It has proved reliable, gives good
      aesthetic results, and reduces treatment costs.

PMID- 7824604
TI  - Flow-through anterior thigh flaps for one-stage reconstruction of soft-tissue
      defects and revascularization of ischemic extremities.
AB  - "Flow-through" anterior thigh flaps are used to reconstruct defects accompanied
      by major vessel damage in the extremities. These flaps have long flow-through
      pedicle vessels (which are the descending branch of the lateral circumflex
      femoral system) that can be interposed into the vascular gaps in the extremities
      and are composed anatomically of the rectus femoris muscle. The defects of eight
      patients were repaired successfully with flow-through anterior thigh flaps, which
      were from 10 to 30 cm in length and 7 to 15 cm in width. The advantages of these
      flaps are (1) the damaged main vessels (< 20 cm in length) can be reconstructed
      simultaneously with large skin defects (up to 30 cm in length and 15 cm in
      width), (2) double arterial inflow by means of both ends of the pedicle artery
      ensures safe blood circulation of the flap, (3) the lateral circumflex femoral
      system, the pedicle of the anterior thigh flaps, can be used for chimeric
      composite flaps for the reconstruction of composite defects with major vessel
      loss in the extremities, (4) two concomitant veins can be used as a drainage
      system in extremities with severe edema, and (5) multistage flap transfers are
      possible to repair recurring defects in the extremities with a single major
      vessel using additional transection and pedicle interposition.

PMID- 7824605
TI  - Free-tissue transfer with the aid of loupe magnification: experience with 251
      procedures.
AB  - Eight years ago, the principal author (Shenaq) began employing high-power ocular
      loupes for microvascular anastomoses. Subsequently, 251 free-tissue transfers
      were performed with loupes as the sole means of magnification. Procedures
      included free flaps, toe-to-hand transfers, and digital replantations, with the
      external diameter of the vascular pedicles averaging 1.5 mm. Analysis of the
      series revealed a 97.2 percent overall success rate, a 1.2 percent partial flap
      necrosis rate, and an 8.3 percent revision rate for anastomoses (during the
      initial operative procedure), which compare favorably with the success rates
      frequently cited for microscope-assisted procedures. The most favorable results
      were achieved with free flaps and toe-to-hand transfers with 98.5 and 96.4
      percent success rates, respectively. The 79.2 percent survival rate achieved with
      digital replantation falls within the range (74.0 to 94.2 percent) reported in
      the literature. This experience indicates that in practiced hands, high-power
      ocular loupes provide an alternative to the operating microscope for
      microvascular anastomosis of vessels 1.0 mm or greater in diameter. Loupe use is
      advocated on the grounds of cost-effectiveness, portability, and operator
      freedom.

PMID- 7824606
TI  - Comparison of the operating microscope and loupes for free microvascular tissue
      transfer.
AB  - A retrospective study of 200 consecutive free microvascular tissue transfers over
      a 3-year period was done to compare the performance of free-tissue transfers with
      loupes and with the operating microscope. One-hundred and nineteen flaps (59.5
      percent) were performed under 3.5 x loupe magnification and 81 under the
      operating microscope (40.5 percent). The magnification selection process was
      based on cumulative past experience, with all early anastomoses performed with
      the microscope and the vast majority of the more recent operations performed with
      loupe magnification. Loupes were used preferentially for head and neck
      reconstruction and breast reconstruction. The microscope was required for
      performing vascular anastomoses on children and on vessels less than or equal to
      1.5 mm in diameter. Results were compared with respect to etiology of defect,
      type of flap, age of patient, free-flap success, complications, and overall
      success of the reconstruction. There was no difference in outcome between the two
      groups, with free-flap success rates of 99 percent for both the loupe and the
      microscope groups. We believe that our success with loupe-only free-tissue
      transfers is attributable to our prior considerable experience with the
      microscope. We would caution that comfort and experience with microanastomoses
      under the operating microscope should be obtained prior to beginning a loupe-only
      experience.

PMID- 7824607
TI  - Transfusion requirements for craniosynostosis surgery in infants.
AB  - Retrospective review of the records of 73 consecutive young children who
      underwent craniosynostosis surgery between 1978 and 1992 in one center was
      conducted to determine transfusion requirements, to document morbidity, and to
      identify causative variables associated with transfusion. Operative age and
      weight, affected suture(s), craniofacial surgeon, neurosurgeon, anesthesiologist,
      preoperative and postoperative hematocrit, and transfusion volumes of blood and
      crystalline products were recoded. Transfusion volumes were converted to percent
      estimated red cell mass for analysis. Affected sutures were unicoronal (22),
      sagittal (17), bicoronal (11), multiple (11), metopic (10), and lambdoid (2).
      Mean operative age was 6.4 months. Mean preoperative hematocrit was 34 percent.
      Eighty percent of patients were discharged with hematocrit of 29 percent or
      greater. Discharge hematocrit was unrelated to year of surgery. Mean
      intraoperative transfusion was 72.1 +/- 56.6 percent estimated red cell mass.
      Transfusions differed statistically among suture(s), neurosurgeons, and
      anesthesiologists. Extensive cranio-orbital surgery for synostosis in young
      children does not produce excessive hemorrhage or transfusion morbidity. The
      anesthesiologist and neurosurgeon may be equally or more important than the
      affected suture(s) as causal variables in transfusion.

PMID- 7824608
TI  - A study of intracranial volume in Apert syndrome.
AB  - The present study was undertaken to characterize the intracranial volume in
      patients with Apert syndrome. Radiographic and CT-based techniques for measuring
      intracranial volume were found to show close correlation when validated in dry
      normal adult skulls. A standard-deviation score of intracranial volume,
      determined from CT scans in 20 patients with Apert syndrome from birth to 30
      years of age, was calculated with reference to a normative database of age- and
      sex-matched controls. Analysis of the data showed no significant difference in
      standard-deviation score between Apert patients with or without ventriculomegaly,
      before or after cranial vault surgery, or between male and female patients. The
      mean standard-deviation score among all Apert CT scans compared with normative
      data was 3.1, which was highly significant (p < 0.001). However, the growth
      curves showed no significant difference in intracranial volume between Apert and
      normal patients below 3.5 months of age. In summary, intracranial volume in Apert
      syndrome is within normal range at birth but increases to greater than 3 standard
      deviations above normal after 3.5 months of age, a finding independent of cranial
      vault surgery.

PMID- 7824610
TI  - Does the pulsed tunable dye laser have a role in the management of infantile
      hemangiomas? Observations based on 3 years' experience.
AB  - Over a 3-year period, 50 patients with strawberry hemangiomas and 7 patients with
      postinvolutional redness or telangiectasia were treated with the SPTL-1 laser
      (Candela Corporation, Wayland, Mass.). The SPTL-1 laser emits pulsed light at a
      wavelength of 585 nm with a pulse duration of 450 ms. Lesions with a superficial
      red component were treated even if they had a significant subcutaneous component;
      however, wholly subcutaneous lesions were excluded. The series included 42 female
      patients aged between 1 and 72 months (mean 14 months) and 8 male patients aged
      between 3 and 12 months (mean 7 months). The mean number of treatments
      administered was 3.8 (range 1 to 8), and the average number of pulses per patient
      was 55 (range 2 to 350). This series also included 7 patients (6 female and 1
      male) with postinvolutional redness or telangiectasia with a mean age of 12 years
      (range 2 to 23 years). They received an average of 3.4 treatments per patient
      (range 2 to 8) with an average of 35 pulses per treatment session (range 3 to
      150). In this study group, life-threatening complications secondary to the
      hemangioma were rare in that only one patient suffered from an airway obstruction
      requiring a tracheostomy and three patients suffered from complete visual
      occlusion. A significant improvement in color was achieved in 30 patients (53
      percent), but there was no appreciable reduction in bulk in any of the lesions
      despite repeated exposure to laser light.

PMID- 7824609
TI  - Electromyographic study of functional recovery of free vascularized muscles
      grafted to the face.
AB  - The functional recovery of gracilis muscles grafted for treatment of facial
      paralysis in combination with a cross-face nerve graft was evaluated on the basis
      of electromyography in 98 cases. Initial action potentials were recorded, on
      average, 8 months after transplantation. There was a tendency for such potentials
      to appear earlier in the case of patients who finally attained good muscle
      activity. Action potentials were polyphasic in the early stage and of short
      duration and low amplitude. An increase in the amplitude and duration of
      potentials and a shortening of the distal latency were observed with increase in
      the numbers of reinnervated muscle fibers. Thereafter, there was a tendency
      toward decreases in the duration and number of spikes due to the increasing
      similarity in the distal latency of each neuromuscular unit. The grafted gracilis
      muscles attained a stable state about 1 year after the initial recording of
      action potentials. It was expected that spontaneous action potentials during rest
      might serve to indicate the condition of reinnervation. Their absence during the
      first few months after transplantation may suggest necrosis of the grafted
      muscle, while those of long duration and high amplitude observed after 1
      postoperative year may be suggestive of disturbance in the reinnervation process.
      In this study, we could not find any significant difference in the reinnervation
      process between that of a gracilis muscle grafted following a cross-face nerve
      graft and a muscle reinnervated following nerve transection and repair. We
      therefore believe that free gracilis muscle transplantation combining a cross
      face nerve graft is appropriate for the reconstruction of muscle function.

PMID- 7824611
TI  - Removal of colored tattoos with the Q-switched alexandrite laser.
AB  - The Q-switched alexandrite laser at 760 nm and 50- to 100-ns pulse duration has
      been shown to effectively remove blue-black as well as green, red, and mauve in
      seven human subjects with colored tattoos. An average of 9.0 treatments were
      required to completely remove the green pigment at an average fluence of 5.80
      J/cm2 compared with an average of 9.7 treatments at an average fluence of 6.10
      J/cm2 for red and an average of 10 treatments at an average fluence of 6.20 J/cm2
      for mauve. Orange and yellow were unaffected by the alexandrite laser over a
      range of fluences tested.

PMID- 7824612
TI  - Women surgeons: career and lifestyle comparisons among surgical subspecialties.
AB  - A national survey of 459 women surgeons yielded a 91.3 percent response rate. The
      largest subspecialties were obstetrics-gynecology (41 percent), ophthalmology (21
      percent), and general surgery (12 percent). Representation in all "other"
      surgical specialties was small (26 percent). A comparison of career and lifestyle
      patterns among the four major subspecialties demonstrated no differences in
      marital status, although ophthalmologists were least likely to remain childless
      (32 percent) and general surgeons most likely (58 percent). Surgeons in
      obstetrics-gynecology worked the longest hours, and those in ophthalmology worked
      the shortest hours. No subspecialty differences were reported in quality-of-life
      parameters.

PMID- 7824613
TI  - The pregnant plastic surgical resident: results of a survey of women plastic
      surgeons and plastic surgery residency directors.
AB  - Pregnancy during plastic surgery residency poses unique challenges to the
      resident herself, to her resident colleagues, and to her residency director.
      Studies of the effects of pregnancy have been conducted that have combined all
      medical specialties or have included all surgeons as a statistically uniform
      group. The Women Plastic Surgeons' Caucus Committee of the American Society of
      Plastic and Reconstructive Surgeons has conducted a survey in order to obtain
      objective data on maternal fetal complications, time off work, maternal leave
      policies, call coverage, and other important issues. Response rates were 40
      percent for the women residents and 45 percent for the program directors
      surveyed. The results show a 57 percent overall complication rate (excluding
      miscarriages), a 26 percent elective abortion rate, and a 33 percent infertility
      rate in women plastic surgeons, numbers that are higher than those currently in
      the literature. Data obtained regarding issues such as time off work, planning of
      pregnancy, call coverage, productivity and income, perceived peer support,
      program directors' opinions and policies, and possible solutions that might
      provide a mutually rewarding outcome are presented for discussion.

PMID- 7824614
TI  - Experimental orthotopic transplantation of vascularized skeletal allografts:
      functional assessment and long-term survival.
AB  - Vascularized skeletal tissue allografts would greatly expand the domain of
      reconstructive surgery. Few studies to date have examined the functional aspects
      of these allografts or their long-term fate. An orthotopic transplant model of
      rat distal femur and surrounding muscular cuff was developed to assess graft
      function in fracture healing and weight bearing. Isografts (RT1l to RT1l, n =
      40), weak-barrier allografts (RT1l to RT1lv, n = 40), and strong-barrier
      allografts (RT1l to RT1n, n = 40) were transplanted. As the histocompatibility
      barrier increased between the donor and recipient animals, the graft viability
      and performance deteriorated according to radiographic, histologic, and
      immunologic analyses. Administration of cyclosporine led to survival of strong
      barrier allografts similar to that of isografts. A long-term study of these
      allografts (RT1l to RT1n) was then performed on various immunosuppressive
      regimens. After an initial 10-week course of cyclosporine to achieve bony union
      and remodeling, subsequent cessation (n = 20) or intermittent "pulsing" (n = 20)
      of the immunosuppressant was insufficient in maintaining graft survival. However,
      graft viability and function were preserved through 1 year on continuous daily
      cyclosporine (n = 32). There was no evidence of host renal or hepatic toxicity by
      serum chemistry or histologic sections. Thus long-term survival of functional
      skeletal allografts was achieved in this orthotopic model without significant
      host toxicity from immunosuppression.

PMID- 7824615
TI  - Histologic comparison of breast implant shells with smooth, foam, and pillar
      microstructuring in a rat model from 1 day to 6 months.
AB  - The purpose of this study was to determine the soft-tissue response to silicone
      breast implants with different surface morphologies and to correlate implant
      microtexturing with capsular formation. Using a rat model, we inserted breast
      implants having three types of shells: micropillared, silicone foam, and smooth
      silicone (control). We used 96 adult male Sprague-Dawley rats weighing between
      250 and 300 gm. Thirty-two rats were assigned to each of the three shell groups.
      Within each shell group, 4 rats were implanted for 24 hours, 4 for 4 weeks, 4 for
      8 weeks, 4 for 12 weeks, 4 for 16 weeks, 4 for 20 weeks, and 4 for 24 weeks. The
      rats were sacrificed at the end of each time interval, and periprosthetic tissue
      was obtained for histologic analysis. Our results show a stable soft-tissue
      response with some macrophages and fibroblasts for the smooth silicone shell
      group; capsule thicknesses were 10 to 12 cells with interwoven collagen. The
      silicone foam prolonged the active cellular response with regard to macrophages,
      fibroblasts, and multinucleated giant cells, along with random collagen
      deposition and alternating thin and thick capsular areas. The micropillar group
      had a more stable cellular response, with macrophages and fibroblasts, along with
      disruption of the long-range orientation of collagen fibers.

PMID- 7824616
TI  - Complications related to retained breast implant capsules.
AB  - Citing evidence that breast implant-related capsules resolve uneventfully,
      surgeons have elected to leave the capsules in place when implants are removed
      because capsulectomy adds both morbidity and expense to the procedure. However,
      recent clinical and histopathologic evidence suggests that uneventful resolution
      is not always the case, and several potential problems may arise from retained
      capsules after removal of the implant. Retained implant capsules may result in a
      spiculated mass suspicious for carcinoma, dense calcifications that obscure
      neighboring breast tissue on subsequent imaging studies, and cystic masses due to
      persistent serous effusion, expansile hematoma, or encapsulated silicone filled
      cysts. Furthermore, retained capsules are a reservoir of implant-related foreign
      material in the case of silicone gel-filled implants and textured implants
      promoting tissue ingrowth. To avoid complications from retained capsules, total
      capsulectomy or postoperative surveillance should be offered to patients.

PMID- 7824617
TI  - Short gracilis myocutaneous flaps for vulvoperineal and inguinal reconstruction.
AB  - From October of 1990 to April of 1993, 16 short gracilis myocutaneous flaps and 1
      short gracilis muscular flap were used to reconstruct vulvoperineal, inguinal,
      perineal, and ischial soft-tissue defects. Five of the 6 bilateral myocutaneous
      flaps were used for vulvoperineal reconstruction after radical vulvectomy
      combined with partial vaginectomy and one radical vulvectomy. Four unilateral
      myocutaneous flaps and one muscular flap were used for inguinal, suprapubic,
      ischial, and perineal reconstruction after release of contracted scar or excision
      of an ischial pressure sore. The immediate complications consisted of partial
      necrosis of the distal third of the cutaneous tissue in 6 patients, 1 superficial
      cutaneous necrosis, and superficial wound infection in 7 patients. The muscular
      portion of the flaps all survived. The follow-up period was from 6 to 27 months.
      The short gracilis flap has greater mobility than the classically described
      gracilis flap. On the basis of the functional and cosmetic results, the short
      gracilis flap is an excellent alternative to the more bulky classic gracilis
      flap.

PMID- 7824618
TI  - Junk medicine in the courtroom.

PMID- 7824619
TI  - Cosmetic trauma surgery.

PMID- 7824620
TI  - Late infection following aesthetic malar augmentation with proplast implants.
AB  - Two cases of late infection following aesthetic malar augmentation with Proplast
      implants are described. The etiology appears to be contamination because of
      erosion of the implants through the thin wall of the anterior maxilla. This
      problem might be avoided by confining placement of the implant over the thick
      portion of the zygoma.

PMID- 7824621
TI  - Simultaneous coverage of two separate defects with two free hemiflaps harvested
      from one latissimus dorsi muscle.
AB  - The latissimus dorsi flap is useful for a variety of reconstructions with
      splitting and tailoring of the muscle. It can be a good donor muscle for the
      reconstruction of two separate defects. Two patients with defects over
      anatomically remote sites were reconstructed using two muscle flaps harvested
      from one latissimus dorsi muscle and are discussed.

PMID- 7824622
TI  - Usefulness of hard palate mucosa graft as nasal lining in alar reconstruction.
AB  - A hard palate mucosa graft was used as nasal lining for alar reconstruction in
      six patients. In five of the six patients, the "take" of the graft was complete.
      The nasal cavity was reconstructed satisfactorily, and no nasal obstruction was
      observed and no collapse of the nasal cavity was found in breathing because of
      the stiffness and thinness of the grafted mucosa. None of the patients suffered
      from erosion or irritation of the graft during the postoperative period. The
      palate donor site healed in 3 to 5 weeks, and no irritation or ulceration was
      seen after the healing. The hard palate mucosa can be considered as a lining
      material in alar reconstruction.

PMID- 7824623
TI  - Transparent gasbag tie-over for persistent pressure and inspection in free skin
      grafting.
AB  - A simple tie-over dressing using a transparent gasbag, which has been used
      successfully in skin grafting on rabbits and human beings, allows objective
      pressure survey and subjective direct inspection of the underlying grafted skin.
      Moreover, if hematoma or any other complication is recognized, the gasbag can be
      deflated and removed, being reapplied after the hematoma is expressed or the
      complication is treated.

PMID- 7824624
TI  - Pharyngoesophageal reconstruction with a tensor fasciae latae free flap.
AB  - This report describes our experience with the use of a tensor fasciae latae flap
      in total reconstructions of the hypopharynx and cervical esophagus. This flap is
      durable, reliable, and easy to elevate. Moreover, it is possible to obtain a
      tight two-layer closure of the circumferential suture lines by means of the
      vascularized fascia. We think this flap will be one of the methods of choice in
      reconstructions of the hypopharynx and cervical esophagus.

PMID- 7824625
TI  - The physiologic basis for nonconventional vascular perfusion.
AB  - It is traditionally thought that the exchange of oxygen occurs only at the
      capillary level, with both arterial inflow and venous outflow required. However,
      as early as 1970, studies have indicated that significant arteriolar and venular
      diffusion of O2 and CO2 occurs. The precapillary and postcapillary diffusion of
      oxygen and carbon dioxide and their potential regulation via the Bohr effect are
      key elements in understanding the success of nonconventional vascular perfusion
      (arterialized venous, total arterial, total venous), where the capillary
      circulation is bypassed. In retrograde "reverse-flow" island flaps, there is an
      anterograde blood flow through the capillary bed, with nonconventionally reversed
      flow within the arterial and venous systems, respectively. The reversal of venous
      flow is best explained as a combination of valvular insufficiency and the
      existence of vein-vein bypass channels via the venae comitantes.

PMID- 7824626
TI  - Hemorrhagic cyst of the orbit as a complication of prosthetic orbital floor
      implant.

PMID- 7824627
TI  - Harvesting iliac bone.

PMID- 7824629
TI  - Silicone gel as an adjuvant.

PMID- 7824628
TI  - The multiplane face lift.

PMID- 7824630
TI  - A new technique for closing wounds after surgery for breast melanoma.

PMID- 7824631
TI  - Fire in the operating room.

PMID- 7824632
TI  - Choice of drugs and sequence of their use during and after microsurgical
      autografting.

PMID- 7824633
TI  - Desmoid tumor of the breast.

PMID- 7824634
TI  - Intranasal administration of midazolam with a dinosaur toy.

PMID- 7824635
TI  - The vanished vagina: an unusual case of abdominal mucocele.

PMID- 7824636
TI  - A new technique to secure an entirely buried subcuticular suture.

PMID- 7824637
TI  - Construction of a neoclitoris in male transsexuals.

PMID- 7824638
TI  - Polysorbate as an adjunctive chemical in the trichloroacetic acid peel.

PMID- 7824639
TI  - Microphotography: a simple innovation.

PMID- 7824640
TI  - Ferromagnetic artifact from a tissue expander used for breast reconstruction.

PMID- 7824641
TI  - Aesthetic indications for botulinum toxin injections.

PMID- 7824642
TI  - Morality, ethics, and the American Board of Plastic Surgery.

PMID- 7824643
TI  - Induction of ethylene biosynthesis in Nicotiana tabacum by a Trichoderma viride
      xylanase is correlated to the accumulation of 1-aminocyclopropane-1-carboxylic
      acid (ACC) synthase and ACC oxidase transcripts.
AB  - Xylanase (EIX) from the fungus Trichoderma viride elicits ethylene biosynthesis
      in leaf tissues of Nicotiana tabacum cv Xanthi but not in cv Hicks. The increase
      in ethylene biosynthesis is accompanied by an accumulation of 1-aminocyclopropane
      1-carboxylic acid (ACC), an increase in extractable ACC synthase activity, and
      increases in ACC synthase and ACC oxidase transcripts. Priming of increases in
      ACC synthase and ACC oxidase transcripts. Priming of leaves with ethylene (120
      microL/L, 14 h) sensitizes the tissue, resulting in an enhanced response to EIX
      and increases in both the in vivo ACC oxidase activity and ACC oxidase transcript
      level. EIX and ethylene independently induce ACC oxidase. Inhibition of ethylene
      biosynthesis by aminoethoxyvinylglycine is not accompanied by a reduction in ACC
      oxidase transcript level, indicating that ethylene biosynthesis is not required.
      In contrast to the differential induction of ethylene biosynthesis by EIX in
      Xanthi versus Hicks cultivars, both cultivars respond to a chemical stress
      (induced by CuSO4) by enhancing ethylene production. This induction is
      accompanied by an increase in ACC synthase transcript but not in that of ACC
      oxidase.

PMID- 7824644
TI  - Arabidopsis thaliana expresses three divergent Srp54 genes.
AB  - The Arabidopsis thaliana Srp54 gene family was determined to consist of three
      genes, all of which were cloned and sequenced. In addition, cDNAs corresponding
      to two of the genes were obtained. To our knowledge this is the first description
      of multiple Srp54 genes within an organism. In contrast to the situation in
      mammals, where there are only three amino acid differences between the mouse and
      canine sequences, there was significant amino acid sequence diversity among the
      genes, particularly in the methionine-rich region of the protein, which is the
      region responsible for binding to the 7S RNA of the signal recognition particle
      and to the signal sequence of newly synthesized proteins. The amino acid
      sequences of the GTP-binding domains of the three clones were 86% identical,
      whereas the methionine-rich domains were only 65% identical. RNA gel blots of
      various tissues and developmental stages hybridized with gene-specific probes
      revealed that all three genes were expressed in all the tissues investigated.
      There were, however, quantitative differences in expression levels.

PMID- 7824646
TI  - Purification and characterization of pea seedling amine oxidase for
      crystallization studies.
AB  - Pea (Pisum sativum L.) seedling amine oxidase (EC 1.4.3.6) is the first amine
      oxidase to be crystallized that diffracts to atomic resolution (2.5 A). Extensive
      modifications of a published purification procedure were necessary to obtain
      protein that would give diffraction-quality crystals. Here we report the improved
      purification and also use this high-purity protein to reexamine some fundamental
      characteristics of pea seedling amine oxidase. The extinction coefficient at 280
      nm (epsilon 1%(280)) and the molecular mass of the protein are investigated by a
      variety of techniques, yielding epsilon 1%(280) = 20 cm-1 and a mass 150 +/- 6
      kD. In addition, the stoichiometry of the metal and organic cofactors, Cu(II) and
      6-hydroxy dopa (Topa) quinone, respectively, is examined. The ratio of
      Cu(II):Topa:protein monomer is found to be 1:1:1.

PMID- 7824645
TI  - Biosynthesis of defense-related proteins in transformed root cultures of
      Trichosanthes kirilowii Maxim. var japonicum (Kitam.).
AB  - We have established transformed ("hairy") root cultures from Trichosanthes
      kirilowii Maxim. var japonicum Kitam. (Cucurbitaceae) and four related species to
      study the biosynthesis of the ribosome-inactivating protein trichosanthin (TCN)
      and other root-specific defense-related plant proteins. Stable, fast-growing root
      clones were obtained for each species by infecting in vitro grown plantlets with
      Agrobacterium rhizogenes American Type Culture Collection strain 15834. Each
      species accumulated reproducibly a discrete protein pattern in the culture
      medium. Analysis of the extracellular proteins from T. kirilowii var japonicum
      root cultures showed differential protein accumulation in the medium during the
      time course of growth in batch cultures. Maximum protein accumulation,
      approaching 20 micrograms/mL, was observed at mid-exponential phase, followed by
      a degradation of a specific protein subset that coincided with the onset of
      stationary phase. Two major extracellular proteins and one intracellular protein,
      purified by ion-exchange and reverse-phase high-performance liquid
      chromatography, were identified as class III chitinases (EC 3.2.1.14) based on N
      terminal amino acid sequence and amino acid composition homologies with other
      class III chitinases. The Trichosanthes chitinases also showed reactivity with a
      cucumber class III chitinase antiserum and chitinolytic activity in a glycol
      chitin gel assay. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and
      western blot analysis of intracellular proteins showed that normal and
      transformed T. kirilowii var japonicum roots accumulated only low levels of TCN
      (approximately 0.5% total soluble protein). Storage roots from the plant
      displayed protein and antigen patterns different from root cultures and produced
      TCN as the dominant protein. Roots undergoing secondary growth and
      differentiation exhibited patterns similar to those of storage roots, including
      increased TCN levels, indicating that high production of TCN is associated with
      induction of secondary growth in roots.

PMID- 7824647
TI  - Nucleotide sequence of a nuclear tRNA(Gly) (GCC) gene of a higher plant, Ragi
      (Eleucine coracana).

PMID- 7824648
TI  - Isolation and characterization of a cDNA encoding ribosomal protein S16 from
      cotton (Gossypium hirsutum L.).

PMID- 7824649
TI  - cDNA cloning and nucleotide sequences of alpha 1 and alpha 2 thionins from
      hexaploid wheat endosperm.

PMID- 7824650
TI  - RNA editing of the tobacco mitochondrial orf38/220.

PMID- 7824651
TI  - cDNA sequence of a protein kinase from the inducible crassulacean acid metabolism
      plant Mesembryanthemum crystallinum L., encoding a SNF-1 homolog.

PMID- 7824652
TI  - lox1:Ps:2, a Pisum sativum seed lipoxygenase gene.

PMID- 7824653
TI  - Cloning and sequencing of a novel serine/threonine protein kinase in Arabidopsis
      thaliana.

PMID- 7824654
TI  - cDNA and derived amino acid sequence of the chloroplastic copper/zinc-superoxide
      dismutase from aspen (Populus tremuloides).

PMID- 7824655
TI  - The fate of inflorescence meristems is controlled by developing fruits in
      Arabidopsis.
AB  - The relationship between fruit development and the proliferative capacities of
      inflorescence meristems has been examined in Arabidopsis thaliana. In the wild
      type Landsberg erecta (Ler) line, flower production ceases coordinately on all
      inflorescence branches by a process we have designated global proliferative
      arrest (GPA). Morphological studies indicate that GPA involves a cessation of
      proliferative activity at the meristems, but a retention of the structural
      characteristics of the proliferating meristems. GPA does not occur in the male
      sterile (ms1-1) line, nor in wild-type Ler when fruits are surgically removed. In
      these cases, inflorescence meristems continue to proliferate, ultimately
      terminating by a different process, designated terminal differentiation, in which
      disruptions in patterning at the apex are followed by the loss of the
      inflorescence meristem. We present an argument that GPA is mediated by a specific
      communication system between inflorescence meristems and developing fruits.
      Analysis of reduced-fertility mutants provided evidence that GPA is dependent on
      seed development specifically. Mutations conferring hormone deficiency or
      insensitivity did not disrupt the correlative interactions leading to GPA.

PMID- 7824656
TI  - Phenylalanine ammonia-lyase in tobacco. Molecular cloning and gene expression
      during the hypersensitive reaction to tobacco mosaic virus and the response to a
      fungal elicitor.
AB  - A tobacco (Nicotiana tabacum L. cv Samsun NN) cDNA clone coding the enzyme
      phenylalanine ammonia-lyase (PAL) was isolated from a cDNA library made from
      polyadenylated RNA purified from tobacco mosaic virus (TMV)-infected leaves.
      Southern analysis indicated that, in tobacco, PAL is encoded by a small family of
      two to four unclustered genes. Northern analysis showed that PAL genes are weakly
      expressed under normal physiological conditions, they are moderately and
      transiently expressed after wounding, but they are strongly induced during the
      hypersensitive reaction to TMV or to a fungal elicitor. Ribonuclease protection
      experiments confirmed this evidence and showed the occurrence of two highly
      homologous PAL messengers originating from a single gene or from two tightly co
      regulated genes. By in situ RNA-RNA hybridization PAL transcripts were shown to
      accumulate in a narrow zone of leaf tissue surrounding necrotic lesions caused by
      TMV infection or treatment with the fungal elicitor. In this zone, no cell
      specificity was observed and there was a decreasing gradient of labeling from the
      edge of necrosis. Some labeling was also found in various cell types of young,
      healthy stems and was shown to accumulate in large amounts in the same cell types
      after the deposition of an elicitor solution at the top of the decapitated plant.

PMID- 7824657
TI  - Modulation of cysteine biosynthesis in chloroplasts of transgenic tobacco
      overexpressing cysteine synthase [O-acetylserine(thiol)-lyase].
AB  - Cysteine synthase [O-acetyl-L-serine(thiol)-lyase, EC 4.2.99.8] (CSase), which is
      responsible for the terminal step of cysteine biosynthesis, catalyzes the
      formation of L-cysteine from O-acetyl-L-serine (OAS) and hydrogen sulfide. Three
      T-DNA vectors carrying a spinach (Spinacia oleracea) cytoplasmic CSase A cDNA (K.
      Saito, N. Miura, M. Yamazaki, H. Horano, I. Murakoshi [1992] Proc Natl Acad Sci
      USA 89: 8078-8082) were constructed as follows: pCSK3F, cDNA driven by the
      cauliflower mosaic virus (CaMV) 35S RNA promoter with a sense orientation;
      pCSK3R, cDNA driven by the CaMV 355 promoter with an antisense orientation;
      pCSK4F, cDNA fused with the sequence for chloroplast-targeting transit peptide of
      pea ribulose-1,5-biphosphate carboxylase small subunit driven by the CaMV 35S
      promoter with a sense orientation. These chimeric genes were transferred into
      tobacco (Nicotiana tabacum) with Agrobacterium-mediated transformation, and self
      fertilized progeny were obtained. CSase activities in cell-free extracts of
      pCSK3F and pCSK4F transformants were 2- to 3-fold higher than those of control
      and pCSK3R plants. CSase activities in chloroplasts of pCSK4F transformants were
      severalfold higher than those of control and pCSK3F plants, indicating that the
      foreign CSase protein is transported and accumulated in a functionally active
      form in chloroplasts of pCSK4F plants. Isolated chloroplasts of a pCSK4F
      transformant had a more pronounced ability to form cysteine in response to
      addition of OAS and sulfur compounds than those of a control plant. In
      particular, feeding of OAS and sulfite resulted in enhanced cysteine formation,
      which required photoreduction of sulfite in chloroplasts. The enhanced cysteine
      formation in a pCSK4F plant responding to sulfite was also observed in leaf
      discs. In addition, these leaf discs were partially resistant to sulfite
      toxicity, possibly due to metabolic detoxification of sulfite by fixing into
      cysteine. These results suggested that overaccumulated foreign CSase in
      chloroplasts could modulate biosynthetic flow of cysteine in response to sulfur
      stress.

PMID- 7824659
TI  - Regulation of BN115, a low-temperature-responsive gene from winter Brassica
      napus.
AB  - The genomic clone for BN115, a low-temperature-responsive gene, was isolated from
      winter Brassica napus and its sequence was determined. A 1.2-kb fragment of the
      5' regulatory region (from bp -1107 to +100) was fused to the beta-glucuronidase
      (GUS) reporter gene and BN115-promoted GUS expression was observed in green
      tissues of transgenic B. napus plants only after incubation at 2 degrees C. No
      expression was observed after incubation at 22 degrees C, either in the presence
      or the absence of ABA. Microprojectile bombardment of winter B. napus leaves with
      a BN115 promoter/GUS construct yielded similar results and was used to analyze a
      series of deletions from the 5' end of the promoter. Results obtained from
      transient expression studies showed that the low-temperature regulation of BN115
      expression involves a possible enhancer region between bp -1107 and -802 and a
      second positive regulatory region located between bp -302 and -274. Deletion
      analyses and results from replacement with a truncated cauliflower mosaic virus
      35S promoter suggest that the minimal size required for any maintenance of low
      temperature GUS expression is a -300-bp fragment. Within this fragment are two 8
      bp elements with the sequence TGGCCGAC, which are identical to those present in
      the positive regulatory region of the promoter of the homologous Arabidopsis
      cor15a gene and to a 5-bp core sequence in the low-temperature- and dehydration
      responsive elements identified in the promoter regions of several cold-responsive
      Arabidopsis thaliana genes.

PMID- 7824658
TI  - Circadian oscillations of a transcript encoding a germin-like protein that is
      associated with cell walls in young leaves of the long-day plant Sinapis alba L.
AB  - As part of an attempt to analyze rhythmic phenomena in the long-day plant Sinapis
      alba L. at the molecular level, we have searched for mRNAs whose concentration
      varies as a function of time of day. Differential screening of a cDNA library
      established from mRNAs expressed at the end of the daily light phase with probes
      representing transcripts expressed predominantly in the morning or evening has
      identified one major transcript. The cDNA, Saglp, encodes a predicted 22-kD
      protein with an N-terminal signal sequence. The protein shows homology to germin,
      a protein expressed in wheat embryos after onset of germination. The Saglp mRNA
      level undergoes circadian oscillations in light/dark cycles with maxima between 8
      and 12 PM (zeitgeber time [zt]12-zt16) and minima around 8 PM (zt0). In plants
      grown from seed in constant light, transcript levels are constitutive. In
      constant light regular temperature shifts function as an alternative "zeitgeber"
      to initiate Saglp transcript oscillations. At the cellular level, Saglp
      transcripts are expressed in the epidermis and spongy parenchyma of young leaves,
      and in distinct regions of the epidermis and the cortex in stems and petioles.
      Strong signals are observed in these tissues around zt12, whereas little
      expression is found around zt20, suggesting that the underlying oscillatory
      mechanism(s) operate(s) synchronously in different plant organs. The SaGLP steady
      state protein concentration remains constant over light/dark cycles. Immunogold
      labeling shows that the SaGLP protein is associated with primary cell walls.

PMID- 7824660
TI  - The regulation of gene expression in transformed maize aleurone and endosperm
      protoplasts. Analysis of promoter activity, intron enhancement, and mRNA
      untranslated regions on expression.
AB  - Gene expression in the aleurone and endosperm is highly regulated during both
      seed development and germination. Studies of alpha-amylase expression in the
      aleurone of barley (Hordeum vulgare) have generated the current paradigm for
      hormonal control of gene expression in germinating cereal grain. Gene expression
      studies in both the aleurone and endosperm tissues of maize (Zea mays) seed have
      been hampered because of a lack of an efficient transformation system. We report
      here the rapid isolation of protoplasts from maize aleurone and endosperm tissue,
      their transformation using polyethylene glycol or electroporation, and the
      regulation of gene expression in these cells. Adh1 promoter activity was reduced
      relative to the 35S promoter in aleurone and endosperm protoplasts compared to
      Black Mexican Sweet suspension cells in which it was nearly as strong as the 35S
      promoter. Intron-mediated stimulation of expression was substantially higher in
      transformed aleurone or endosperm protoplasts than in cell-suspension culture
      protoplasts, and the data suggest that the effect of an intron may be affected by
      cell type. To examine cytoplasmic regulation, the 5' and 3' untranslated regions
      from a barley alpha-amylase were fused to the firefly luciferase-coding region,
      and their effect on translation and mRNA stability was examined following the
      delivery of in vitro synthesized mRNA to aleurone and endosperm protoplasts. The
      alpha-amylase untranslated regions regulated translational efficiency in a tissue
      specific manner, increasing translation in aleurone or endosperm protoplasts but
      not in maize or carrot cell-suspension protoplasts, in animal cells, or in in
      vitro translation lysates.

PMID- 7824661
TI  - Evidence for protein phosphatase 1 and 2A regulation of K+ channels in two types
      of leaf cells.
AB  - Ion channels control ion fluxes across membranes, membrane potential, and signal
      transduction between and within cells. Protein kinases and phosphatases are
      important regulators involved in stimulus-response coupling in eukaryotic
      organisms. We have identified in extracts of Vicia faba leaf cells protein
      phosphatase activities inhibited by okadaic acid (OA) and calyculin A (CA), two
      inhibitors of protein phosphatases 1 and 2A. Using whole-cell patch-clamp
      techniques, we have demonstrated that inward K+ currents in guard cells are
      inhibited by nanomolar concentrations of OA or CA, whereas outward K+ currents
      are not affected. However, the same inhibitors enhance the magnitude of outward
      K+ currents in mesophyll cells. A phosphatase antagonist, adenosine-5'-O-(3
      thiotriphosphate), has an effect similar to OA and CA on outward K+ currents in
      mesophyll cells. Our findings suggest that protein phosphatases 1 and/or 2A play
      different physiological roles in modulating the activity of K+ channels in
      mesophyll cells and guard cells.

PMID- 7824662
TI  - Expression of a human lactoferrin cDNA in tobacco cells produces antibacterial
      protein(s).
AB  - A suspension tobacco (Nicotiana tabacum L.) cell line was transformed to express
      human lactoferrin, an iron-binding glycoprotein. The transgenic calli produced a
      protein that was significantly smaller than the full-length lactoferrin protein.
      Total protein extracts made from transgenic tobacco callus exhibited much higher
      antibacterial activity than commercially available purified lactoferrin as
      determined by the decrease of colony-forming units when tested with four
      phytopathogenic species of bacteria. Introduction of the lactoferrin gene in crop
      plants may provide resistance against phytopathogenic bacteria.

PMID- 7824663
TI  - [Prof. Dr. med. Hans Strotzka, social psychiatrist, psychotherapist 1917-1994].

PMID- 7824664
TI  - [The place of psychotherapeutic activity in psychiatry].

PMID- 7824665
TI  - [Theses on psychotherapeutic qualification of psychiatrists].
AB  - The creation in Germany of the professional designation of a joint Specialist for
      Psychiatry and Psychotherapy raises a number of questions and problems. The risks
      and chances of the new regulation are discussed by means of six theses. The
      author favours maximum closeness to practice when performing psychotherapeutic
      training of psychiatrists so that these may be enabled to execute all the care
      activities that come up in psychiatry day by day, in a psychodynamically oriented
      manner. In my opinion, however, cooperation between psychiatry and psychoanalysis
      can be successful if a coexistence develops that is upheld and animated by the
      tensions and atmosphere of suspense existing between the two disciplines.

PMID- 7824666
TI  - [Countertransference problems with suicidal patients in inpatient psychiatric
      treatment].
AB  - Transference is an effective protection against suicidal impulses of psychiatric
      patients. However, suicidal patient's highly ambivalent attempts at establishing
      a relationship with the therapist lead to significant transference and
      countertransference problems. During the course of therapy the therapist often is
      used as a selfobject, an experience that alters the narcissistic equilibrium.
      Suicidal patients create a selfobject transference by means of attacks on the
      therapist similar to those they themselves had experienced in their childhoods.
      The hidden attacks are very troublesome to the therapist's own feeling of
      selfworth and his state of self may be changed in the sense of a selfobject
      countertransference.

PMID- 7824667
TI  - [Diagnosis of borderline syndrome in routine clinical practice].
AB  - In this study an evaluation of 36 medical reports of patients diagnosed as
      "Borderline Personality Disorder" was made. The finding of the diagnosis in
      clinical routine is discussed. In consideration of the variations of
      psychopathological states in these patients the authors suggest that there should
      be put more emphasis on the changes of symptoms in the course of a longer time.

PMID- 7824668
TI  - [Clinical, social and political attitude toward the development of neuroses in
      Russia today].

PMID- 7824669
TI  - [Social work in acute psychiatry].
AB  - The present study reports about social work during a 3 month period in a
      psychiatric intensive care unit. The activities of the social worker were
      documented and classified according a special key. 160 patients were admitted and
      diagnosed according to ICD 9 and ICD 10, in about 62% of these patients the
      social worker was involved. The analysis demonstrates that the social worker is
      more active in male patients and in patients with schizophrenic psychosis. This
      report points out the relevance of the social work in a psychiatric intensive
      care unit and the necessity of a good documentation of the social work efforts.

PMID- 7824670
TI  - [Adult neuronal ceroid lipofuscinosis (Kufs disease)--a rare cause of dementia].
AB  - Kufs' disease is a very rare type of neuronal ceroid lipofuscinosis. A case of a
      52 year old man with dementia is described. The cause for patient's dementia was
      the adult type (Kufs' disease) of neuronal ceroid lipofuscinosis. The diagnosis
      based on the histopathological post mortem-examination of the brain-tissue. A
      brother of our patient became ill with the same symptoms and at the same age of
      onset. So we conclude that there is a accumulation in the family.

PMID- 7824671
TI  - [Psychotherapy in transition--from confession to profession. A controversy over a
      remarkable book by Klaus Grawe, Ruth Donati and Friederike Bernauer].
AB  - Grawe, Donati and Bernauer conducted together with 16 female and male coworkers
      the first comprehensive meta-analysis of all the psychotherapeutic studies that
      were available. They examined and evaluated each of a total of 897 studies
      according to 1000 individual parameters. Even before publication, everyone
      concerned took sides, turning the book into a political affair: behavioural
      therapists versus female psychoanalysts, psychologists versus female physicians,
      female scientists versus followers of a "school". Be that as it may, the book by
      Grawe, Bernauer and Donati yields important results which nobody can deny without
      harming the very methods it citicises.

PMID- 7824672
TI  - Preliminary evidence for an association between minor physical anomalies and
      second trimester neurodevelopment in schizophrenia.
AB  - Two types of markers, dermatoglyphics and minor physical anomalies, have been
      used as indicators of problems with fetal neurodevelopment in schizophrenia. The
      degree to which these markers overlap is not known. While it is agreed that
      abnormal dermatoglyphics reflect early second trimester maldevelopment, the
      timing of the development of minor physical anomalies has not been determined.
      Forty-six schizophrenic patients received assessments for minor physical
      anomalies, dermatoglyphics (right-left ridge count asymmetry and total finger
      ridge count), and information processing. Higher scores for minor physical
      anomalies were associated with greater dermatoglyphic asymmetry. Patients who had
      both types of indicators (high minor physical anomalies and dermatoglyphic
      asymmetry) did not differ on information-processing measures from patients who
      had neither. On the basis of the timing of dermatoglyphic development (weeks 14
      22 of gestation), the association between minor physical anomalies and
      dermatoglyphic asymmetry suggests that the relatively high rate of minor physical
      anomalies observed in schizophrenia can be considered to reflect at least second
      trimester maldevelopment.

PMID- 7824673
TI  - Selective attention and response competition in schizophrenic patients.
AB  - Visual distractibility was studied in schizophrenic patients. Subjects had to
      respond to target stimuli while they ignored the visual context, which was either
      congruent, neutral, or incongruent with respect to the target stimulus. Eighteen
      schizophrenic patients and 18 healthy subjects performed this flanker task.
      Schizophrenic patients did not show increased distractibility compared with
      healthy subjects, and both groups showed the same attenuation of visual context
      effects when the spatial distance between target and flanker stimuli was
      increased. The two groups showed the same amount of interference by incongruent
      visual context. Thus, schizophrenic patients did not show enhanced
      distractibility, spatial extension of attention, or response competition. When
      flanker and target stimuli were redundant, the responses of schizophrenic
      patients were less accelerated than those of healthy subjects.

PMID- 7824674
TI  - Cognitive correlates to social cue perception in schizophrenia.
AB  - Previous research has examined social skill learning in schizophrenic patients in
      relation to information-processing deficits and psychiatric symptoms.
      Relationships were examined in the current report between social cue perception,
      thought to be an early and necessary component of skill learning, and various
      information-processing deficits and psychiatric symptoms. Twenty-six inpatients
      with DSM-III-R diagnoses of schizophrenia completed measures of social cue
      perception, cognitive functioning, and psychiatric symptoms. Results showed that
      cue perception was significantly related to measures of early visual processing,
      recognition memory, and psychiatric symptoms of withdrawal/retardation.
      Implications of these findings for future research into the social-perceptual
      deficits of schizophrenic patients are discussed.

PMID- 7824675
TI  - Cluster a personality disorder: a marker of worse treatment outcome of major
      depression?
AB  - This study attempted to identify a specific personality disorder (PD) cluster
      associated with poor outcome after a 4-month course of antidepressant therapy.
      Subjects were 96 consecutive outpatients with major depression. The Structured
      Clinical Interview for DSM-III-R (SCID) was used to make Axis I and Axis II
      diagnoses. To evaluate the net effect of each PD cluster on the outcome of
      depression, a log-linear model was applied. The analysis showed that the presence
      of a PD from cluster A was significantly correlated with the 4-month outcome of
      depression.

PMID- 7824676
TI  - Suicides in California (1968-1977): absence of seasonality in Los Angeles and
      Sacramento counties.
AB  - Since the turn of the century, there have been numerous publications on the
      seasonality of suicide. Rarely has the duration of sunlight exposure or any other
      weather parameter been quantitated in studies of suicide seasonality. To explore
      the relationships between sunlight and suicide, we examined California weather
      and suicide data from 1968 to 1977. Los Angeles County and Sacramento County were
      well-suited to the investigation, as complete data were available for these large
      population centers. There was no evidence of seasonality to suicides in L.A.
      County or Sacramento, despite a pronounced seasonality to weather. To investigate
      the acute temporal effects of weather on suicides, all occurrences of 10
      successive above- or below-average sunshine days were identified. Suicides of for
      intervals of 5 days were then compared by Mann-Whitney analyses for 25 days after
      the selected intervals. For L.A. County, there were no significant findings. For
      Sacramento County, however, there was evidence for sunlight inhibition of
      suicides at days 21-25 after the above-average sunshine. Suicides after 10 days
      of below-average sunshine were increased as much as 70% about the 10-year
      average. Further replication studies with larger data sets are needed for an
      adequate examination of the correspondences of suicide data and weather
      measurements.

PMID- 7824677
TI  - Antidepressant and depressogenic drugs lack consistent effects on hamster
      circadian rhythms.
AB  - The circadian wheel-running rhythm of golden hamsters was monitored during
      chronic oral treatment with four antidepressants and two potentially
      depressogenic agents. Desmethylimipramine shortened the circadian period (tau) by
      0.1 hour. In contrast, clorgyline lengthened tau by 0.1 hour and delayed light
      synchronized wheel-running rhythms by 1.4 hour. Phenelzine, fluoxetine,
      clonidine, and propranolol did not significantly alter light-entrained phase or
      free-running period over a range of doses. Other rhythm parameters were also
      unaffected by antidepressant or depressogenic drugs. These data suggest that mood
      altering drugs do not consistently influence circadian rhythms in the hamster.

PMID- 7824678
TI  - Role of seizure activity in the decreased pineal response to isoproterenol in
      rats chronically treated with electroconvulsive shock.
AB  - Chronic electroconvulsive shock (ECS) has been previously reported to blunt the
      melatonin response to acute isoproterenol administration in rats. To assess
      whether electrically induced seizures are indeed required for the appearance of
      the blunted pineal response to isoproterenol, pineal and serum melatonin levels
      were measured after isoproterenol stimulation in rats treated with ECS (80 mA,
      0.5 sec), subconvulsive shock (15 mA, 0.5 sec), or sham-ECS once per day at 11:30
      12:00 h for 8 days. In ECS-treated rats, both pineal and serum melatonin levels
      after isoproterenol administration were significantly lower than those in sham
      treated animals and in rats receiving subconvulsive shock. Moreover, as compared
      with sham treatment, chronic subconvulsive shock did not affect the melatonin
      response to isoproterenol. These data show that seizure activity is indeed
      required for the ECS-induced decrease in the pineal response to acute beta
      adrenergic stimulation.

PMID- 7824679
TI  - Hamilton Anxiety Rating Scale Interview guide: joint interview and test-retest
      methods for interrater reliability.
AB  - The Hamilton Anxiety Rating Scale (HARS) is the most widely used semistructured
      assessment scale in treatment outcome studies of anxiety. Interrater reliability
      coefficients for the HARS have been previously reported. However, differences in
      the way clinicians assess symptom severity may reduce reliability. A structured
      interview guide--The Hamilton Anxiety Rating Scale Interview Guide (HARS-IG)--was
      developed to standardize clinical probe questions and to minimize interrater
      variance. Joint-interview and test-retest methods of interrater reliability
      assessment were used in a group of 30 inpatients. Intraclass coefficient
      calculations revealed improved interrater agreement with the HARS-IG versus the
      HARS. The findings of this study demonstrate that the HARS-IG is a more reliable
      assessment instrument than the semistructured HARS and that it meets established
      standards of reliability assessment.

PMID- 7824680
TI  - No evidence of linkage between the dopamine D2 receptor gene and schizophrenia.
AB  - The antipsychotic effects of dopamine D2 receptor antagonists (neuroleptics) and
      the psychotomimetic effects of dopamine agonists suggest that a defect of the D2
      receptor gene might be a factor in the etiology of schizophrenia. Fifteen
      families that contained several members suffering from schizophrenia were tested
      for linkage between the D2 receptor gene and schizophrenia. In addition, four
      flanking markers were tested. The mode of inheritance was assumed to be dominant.
      Five different models of the affection status, which ranged from a narrow to a
      broad definition of the affection status, were studied. Linkage analysis was
      carried out with dominant, recessive, and intermediate modes of transmission. Two
      point and multipoint analyses between schizophrenia and the D2 receptor gene
      resulted in log-likelihood differences < -2 for all five models, and linkage
      between this candidate gene and schizophrenia was excluded. A mutation in the D2
      receptor gene itself is therefore extremely unlikely to be related to a higher
      susceptibility to schizophrenia, at least in the present group of families.

PMID- 7824681
TI  - The effects of location cuing on redundant-target processing.
AB  - The present study is concerned with the redundany gain: the observation that
      subjects respond faster to simultaneously presented redundant targets than to
      single targets. This finding is usually interpreted as evidence for parallel,
      self-terminating, unlimited-capacity processing. Alternatively, it has been
      claimed that the reaction-time advantage with redundant targets is simply due to
      spatial uncertainty under single-target conditions. The present study tested this
      hypothesis. In Experiment 1, subjects responded when one, two, or three letters E
      were presented, and refrained from responding when one, two, or three letters F
      were presented. In half of the trials, location uncertainty was eliminated by
      presentation of a line segment at one the locations of the subsequently appearing
      target letters. The results reject the alternative spatial-uncertainty
      explanation: even when the location of the impending target is cued in advance,
      there is no attenuation of the redundancy gain. Experiment 2 served as a control
      experiment and showed a clear redundancy gain, even in conditions in which it was
      ensured that, before display onset, attention was directed to a location of one
      of the impending targets.

PMID- 7824682
TI  - Temporal coordination of alternative and simultaneous aiming movements of
      constrained timing structure.
AB  - Two experiments are reported addressing the preparation and initiation of
      movements with equal or unequal timing properties for both hands. Temporal
      coordination was examined in two movement tasks: one in which both hands
      performed the movements simultaneously (simultaneous aiming task) and one in
      which only one alternative of two possible movements was executed (choice aiming
      task). For each task a different group of subjects was used. Besides the timing
      relationships between both movements, the effects of preparation interval (1, 3,
      and 5 s), the average velocity (7, 14, 17.5, and 70 cm/s), the presence of
      advance information about the required velocity of the movement(s), and practice
      were investigated. Based on the common- and the specific-timing notions, distinct
      hypotheses were tested as to the effects of the variables on the temporal
      coordination as revealed by reaction time. A main result was that the effects of
      timing differences between the hands was task specific. For the choice task the
      data are in agreement with the common-timing notion of coordination, i.e., only
      one timing demand at a time can be prepared, whereas in the simultaneous task
      evidence was obtained for the specific-timing notion, i.e., independent
      preparation and initiation of different timing properties for the hands. However,
      it is argued that the results of the choice task probably do not reflect a
      general inability to prepare movements of different timing requirements for both
      hands, but is related to a task-specific strategy of selective preparation.

PMID- 7824683
TI  - The impact of motor responses on serial-pattern learning.
AB  - Subjects are able to learn even very complex serial patterns in serial-reaction
      time tasks. The investigation of the learning processes behind this phenomenon
      has yielded contradictory results. Some studies have come to the conclusion the
      subjects had learned the sequence of stimuli. Other studies have assumed that the
      sequence of responses had been learned or a combination of both stimuli and
      responses. The present experiments stress the impact of motor responses on serial
      pattern learning. The subjects had to respond to serial targets that were
      presented within a matrix of distractors. The position of each target could be
      predicted from the identity and position of the previous target. If the subjects
      were to learn this pattern, they would be able to speed up the search for the
      target and give faster responses. The results indicated that the relation between
      the target identity and the position of the next target was acquired much better
      by those subjects who had to respond to each target with a special motor
      response. If the same response was required for the relevant targets, knowledge
      of the rule was somewhat fragmentary. To explain these results, mechanisms of
      motor learning and motor planning are discussed. It is assumed that learning of
      the rules occurs if the position changes appear to be effects of different motor
      responses.

PMID- 7824684
TI  - Motor similarity in subject-performed tasks.
AB  - In two experiments, subjects learned action phrases in verbal and subject
      performed tasks. They had to recognize these action phrases among foils that
      denoted either completely different actions, conceptually similar actions, or
      actions that were conceptually and motorically similar. It was found that
      recognition performance was impaired equally after both kinds of learning when
      conceptually similar distractors were used, but was impaired more after subject
      performed-task learning when the distractors were both conceptually and
      motorically similar. The possible contribution of motor information in this
      interaction is discussed.

PMID- 7824685
TI  - Training redundant artificial neural networks: imposing biology on technology.
AB  - One biological principle that is often overlooked in the design of artificial
      neural networks (ANNs) is redundancy. Redundancy is the replication of processes
      within the brain. This paper examines the effects of redundancy on learning in
      ANNs when given either a function-approximation task or a pattern-classification
      task. The function-approximation task simulated a robotic arm reaching toward an
      object in two-dimensional space, and the pattern-classification task was
      detecting parity. Results indicated that redundant ANNs learned the pattern
      classification problem much faster, and converge on a solution 100% of the time,
      whereas standard ANNs sometimes failed to learn the problem. Furthermore, when
      overall network error is considered, redundant ANNs were significantly more
      accurate than standard ANNs in performing the function-approximation task. These
      results are discussed in terms of the relevance of redundancy to the performance
      of ANNs in general, and the relevance of redundancy in biological systems in
      particular.

PMID- 7824686
TI  - [The concept of emerging disease].
AB  - To avoid misinterpretations one should substitute the ambiguous notion of 'new
      disease' with 'emerging disease'. A disease can be classified emergent in at
      least five different historical situations; 1) it existed before it could be
      first identified but was overlooked from a medical point of view because it could
      not be conceptualized as a nosological entity; 2) it existed but was not noticed
      until a quantitative and/or qualitative change in its manifestations; 3) it did
      not exist in a particular region of the world before its introduction from other
      regions; 4) it never existed in a human population but only in an animal
      population; 5) it is completely new--the triggering germ and/or necessary
      environmental conditions did not exist prior to the first clinical
      manifestations. A series of historical examples illustrate this classification.

PMID- 7824687
TI  - [Emerging diseases and demography dynamics].
AB  - The point of view presented in this work is not that of the epidemiologist
      interested in the etiology of diseases and their specific effect on mortality
      rates; but rather the view of the demographer who attempts to establish the
      influence that diseases have on evolution and population dynamics. It is not
      until the 19th century that the 'unification microbienne' of the world is reached
      and one has clinical and statistical data on the major diseases. Consequently, it
      is not possible to have an exact demographic picture of infectious diseases in
      their emerging phase. To understand globally this effect one may create a
      conceptual framework capable of integrating all the aspects of mortality rates:
      genetic, socio-biological and human. The scheme proposed here allows for a
      description and at the same time an evaluation of a given historical situation,
      how a population achieves protection from lethal diseases and what are the
      factors determining receptivity or resistance to a disease. This approach serves
      to study the interdependent relations that link all elements involved in a given
      morbid process.

PMID- 7824688
TI  - Poliomyelitis and infantile paralysis: changes in host and virus.
AB  - Death of motor neurones following invasion of the central nervous system by
      poliovirus may result in paralysis of specific muscles. Virulence may be tested
      by injection into monkeys by routes which bypass natural infection.
      Transmissibility is also very important, but cannot be measured, only inferred.
      An infection may lead to immunity or paralysis. In epidemics, the highest
      incidence among children 0-2 years was 2% and among those over 10 years was 25%:
      these figures fit a model of genetic susceptibility of homozygotes and
      heterozygotes with phenotypic susceptibility increasing with age. Hypogamma
      globulinemics, some neonates and pregnant women are more susceptible than others.
      Intra-muscular injections may increase the risk of paralysis. Strenuous exercise
      and IM injections given when poliovirus has already reached the spinal cord can
      increase the severity of paralysis or convert a non-paralytic attack to
      paralysis. Although vaccines reduced polio in temperate countries, polio was
      thought to be no problem in the tropics. Since 1977 polio has been recognised as
      a massive problem in the third world: because it affects babies and very young
      children, it is properly infantile paralysis.

PMID- 7824689
TI  - Policing hearts of darkness: aspects of the international sanitary conferences.
AB  - Internationalism became an important feature of medicine and medical science
      during the second half of the nineteenth century. Internationalism emerged in a
      climate of nationalism and the latter sometimes affected cooperation, especially
      after the Franco-Prussian War of 1870-71, and the increased imperialism of the
      last third of the century. Against this backdrop, the International Sanitary
      Conferences, beginning with the first one in Paris in 1851, attempted to provide
      guidelines to control the spread of disease, especially cholera and plague.
      Quarantine was seen as a central feature of disease control, but it remained a
      controversial measure, since it disrupted trade and inhibited freedom of
      movement. Most of the early Sanitary Conferences failed to reach agreement, but
      by the early twentieth century, a broader series of control measures began to be
      effected, as knowledge of the mode of spread of infectious diseases was achieved.

PMID- 7824690
TI  - [International health organizations facing the emergence of new infectious
      diseases].
AB  - Throughout history, international health collaboration gradually came into being
      to counteract the emergence of new diseases. This process went through five
      stages.: 1) Quarantine regulations were established for maritime commerce to
      safeguard public health. 2) Scientific data were studied to understand the causes
      of infectious diseases and their modes of transmission; a single solution to the
      problem was not sufficient because of the diversities of the various factors
      triggering these diseases. Furthermore, defensive and protective measures adopted
      in Europe were inadequate after the colonial expansion of European countries. 3)
      If 19th century international health politics were defensive, the aim in the 20th
      century was to fight infectious diseases and to eradicate them. This third phase
      saw the rise of international institutions. These agencies aimed at favouring
      better health organization in individual countries. 4) The World Health
      Organization was founded, the aim being to fight existing epidemics, little
      importance being given to 'emerging diseases'. 5) A series of new infectious
      diseases and the reemergence of old diseases (a consequence of major ecological
      changes) that were thought to be eradicated revealed the need for continuous
      surveillance.

PMID- 7824691
TI  - The emerging histories of AIDS: three successive paradigms.
AB  - Thinking of AIDS as an 'emerging disease' inevitably raises questions of
      comparison. In the United States, we see three main phases in understanding AIDS,
      with each having very different implications for health and social policy. In the
      first, AIDS was conceived of as an epidemic disease, a 'gay plague', by analogy
      to the sudden, devastating epidemics of the past. In the second, it was
      normalized as a chronic disease, similar in many ways to diseases such as cancer.
      In the third, we outline a new understanding of AIDS a slow-moving, long-lasting
      pandemic, a chronic infectious ailment manifested through myriad specific HIV
      related diseases. This new paradigm emphasizes, like the plague model, the
      etiology, transmission, and prevention of disease; like the chronic disease
      model, it is concerned with the clinical management of protracted illness. We do
      criticize, however, both the infectious and chronic disease models for their
      individualistic conceptions of disease and their narrow strategies for disease
      prevention. We further suggest that the traditional distinction between, and
      approaches to, infectious and chronic diseases are problematic and need to be
      rethought for AIDS and other diseases.

PMID- 7824692
TI  - Current status of digital angiography in vascular imaging.
AB  - This article discusses the current usefulness of digital vascular imaging and its
      role in contemporary practice. Topics discussed include intravenous versus intra
      arterial digital subtraction angiography, digital angiographic techniques, and
      clinical applications of digital imaging.

PMID- 7824693
TI  - Neurovascular imaging.
AB  - Neurovascular imaging stresses the role of MR angiography and color flow Doppler
      sonography in selected congenital vascular anomalies, aneurysms, arteriovenous
      malformations, arteriosclerotic cerebrovascular disease, and dural sinus
      thrombosis. The application of North American Symptomatic Carotid Endarterectomy
      Trial criteria to the diagnosis of carotid artery stenosis and the correlations
      among radiograph arteriography, sonography, and MR angiography are reviewed in
      detail. The new clinical advisory on endarterectomy for asymptomatic 60% to 99%
      carotid stenosis is reviewed as well.

PMID- 7824694
TI  - Current status of carbon dioxide angiography.
AB  - The current status of carbon dioxide as an angiographic contrast agent is
      reviewed in this article. The physical characteristics of intravascular carbon
      dioxide, pertinent physiology, and principles of imaging are discussed. In
      addition, the advantages and limitations of carbon dioxide are compared with
      those of iodinated contrast. Examples of diagnostic and therapeutic procedures in
      both the arterial and venous systems show the utility of carbon dioxide
      angiography.

PMID- 7824695
TI  - Contemporary diagnostic approaches to acute pulmonary emboli.
AB  - Because of its availability and familiarity, the V/Q scan remains the most
      frequently used noninvasive screening study for the diagnosis of acute PE. Fast
      CT and MR imaging techniques probably will have more significant roles in the
      future in the diagnosis and management of PE, but limited availability and
      familiarity with these imaging modalities make it impractical to currently
      recommend them as primary screening tools for acute PE. Although the cost and
      time benefits appear to place fast CT ahead of MR imaging, more clinical
      experience and a greater understanding of the imaging nuances and pitfalls of
      interpretation for both fast CT and MR imaging are needed. Medicare
      reimbursements (both technical and professional fees) for a CT or MR scan are
      already competitive with a V/Q scan (Table 2), so that they may ultimately prove
      to be more cost-effective screening modalities for PE than a V/Q scan. Until the
      role for intraarterial DSA becomes further defined with clinical trials and
      outcome analyses, it cannot be recommended as a reference standard for the
      diagnosis of PE. Although conventional pulmonary angiography is associated with a
      1% to 2% major nonfatal complication rate and a 0.1% to 0.5% mortality rate,
      chronic anticoagulation has reported major bleeding complication rates of 1.5% to
      20% at 1 year, and inferior vena cava filters are associated with inferior vena
      cava thrombosis rates of 3% to 25%. Therefore, initiating or withholding therapy
      for the "presumed" presence or absence of PE based on a V/Q scan alone has the
      potential for generating excessive costs and morbidity in a large population of
      patients. Until the validity of fast CT and MR imaging have been proven, a
      pulmonary angiogram is required when there is any doubt about the diagnosis of
      PE. A negative pulmonary angiogram is often more useful in the management of a
      patient than an angiogram that demonstrates PE. By ruling out the presence of PE,
      an alternative and possibly more significant diagnosis will be pursued. Lastly,
      it is necessary for us to define more clearly the term clinically significant PE.
      This is important because fast CT, MR imaging and intraarterial DSA techniques
      can now reliably visualize third order pulmonary artery branches. Whether this
      degree of resolution allows for adequate detection of clinically significant PE
      will only be determined by extensive patient tracking and outcome analyses.

PMID- 7824696
TI  - Intravascular ultrasound. The role in diagnostic and therapeutic procedures.
AB  - Intravascular ultrasound, a relatively new imaging modality, has become part of
      the expanding armamentarium of imaging devices used during both coronary and
      peripheral interventions. Topics discussed in this article include techniques,
      interpretation and validation, applications, and future directions.

PMID- 7824697
TI  - Current status of three-dimensional spiral CT scanning for imaging the
      vasculature.
AB  - Three-dimensional CT angiography is a new modality for minimally invasive
      vascular imaging. Meticulous attention to technique is critical to optimizing
      image quality and achieving diagnostic images. In this article, the properties of
      spiral CT acquisitions, intravenous contrast delivery, and three-dimensional
      rendering techniques, as they pertain to the optimization of CT angiograms, are
      discussed. Next, a review of initial investigations into the clinical
      applicability of CT angiography in the cranium, neck, chest, abdomen, and pelvis
      is provided. Finally, CT angiography is compared with MR angiography and
      conventional angiography.

PMID- 7824698
TI  - Peripheral arterial disease. Evaluation with color flow and duplex sonography.
AB  - This article reviews the expanding role of sonography in the noninvasive
      evaluation of peripheral arterial diseases. Technical aspects, aneurysms,
      pseudoaneurysms, perivascular masses, arteriovenous fistulae, detection of
      arterial conduit occlusion, principles of stenosis detection and grading, bypass
      graft monitoring, and native peripheral arterial disease are among the topics
      discussed.

PMID- 7824699
TI  - Basic concepts in magnetic resonance angiography.
AB  - The field of MR angiography is becoming well-established and is finding its way
      into the general MR imaging practice. The number of acquisition methods and the
      supporting physics can be complex; however, once the basic concepts are
      understood an intuition regarding the basic use of MR angiography and some of the
      tradeoffs such as scan time, resolution, and coverage associated with different
      MR angiography methods can be developed. Table 3 summarizes typical applications
      of several different MR angiography techniques mentioned herein.

PMID- 7824700
TI  - Management of the breast specimen.

PMID- 7824701
TI  - Breath-hold fast spin-echo MR imaging of the liver: a technique for high-quality
      T2-weighted images.

PMID- 7824702
TI  - Probably benign breast nodules: follow-up of selected cases without initial full
      problem-solving imaging.

PMID- 7824703
TI  - Postangiographic femoral artery pseudoaneurysms: further experience with US
      guided compression repair.
AB  - PURPOSE: To assess the efficacy of ultrasound-guided compression repair (UGCR) in
      postcatheterization femoral artery pseudoaneurysms. MATERIALS AND METHODS: One
      hundred thirty-three patients with pseudoaneurysms were considered for UGCR.
      Patients underwent compression with duplex and color Doppler ultrasound.
      Immediate and long-term successes were evaluated. RESULTS: Seven patients were
      not candidates for UGCR. UGCR was technically possible in 117 of the 126 patients
      who were candidates. UGCR was successful in 109 patients. The failure rate was
      significantly higher in patients who were receiving anticoagulant medication (P <
      .001). Pseudoaneurysm size, age, and structure (simple vs multiloculated) had no
      bearing on success or failure. The time required for successful compression was
      not related to treatment with anticoagulants but was related to pseudoaneurysm
      structure. Complications included one case of a distal embolus and two episodes
      of hypotension. CONCLUSION: UGCR is a simple and expedient method for the
      treatment of postcatheterization femoral artery pseudoaneurysms.

PMID- 7824704
TI  - Pulmonary embolism: diagnosis with contrast-enhanced electron-beam CT and
      comparison with pulmonary angiography.
AB  - PURPOSE: To determine the sensitivity and specificity of contrast material
      enhanced electron-beam computed tomography (CT) in the diagnosis of pulmonary
      embolism (PE). MATERIALS AND METHODS: Sixty patients suspected of having PE were
      prospectively evaluated with pulmonary angiography and contrast-enhanced electron
      beam CT. Thirty-eight patients underwent ventilation-perfusion (V-P [also known
      as V/Q]) scanning. The pulmonary vasculature was divided into 12 anatomic zones.
      CT and angiographic findings were correlated on a patient-by-patient basis and
      for each vascular zone. RESULTS: Both studies were negative for PE in 36
      patients. Both studies were positive in 15 patients, with the site of the emboli
      correlating well. Prospective sensitivity of CT was 65%; specificity, 97%;
      positive predictive value, 94%; and negative predictive value, 82%. After review
      of the nine discordant cases, sensitivity and specificity approached 100% for
      clinically important acute PE. CT depicted central and peripheral emboli equally
      well. CT was more sensitive and specific than V-P scanning. CONCLUSION: Electron
      beam CT is a sensitive and specific noninvasive method for the diagnosis of PE.
      It has the potential to replace V-P scanning as the primary screening examination
      for PE.

PMID- 7824705
TI  - Oxygen saturation of blood in the superior mesenteric vein: in vivo verification
      of MR imaging measurements in a canine model. Work in progress.
AB  - PURPOSE: To evaluate the accuracy of magnetic resonance (MR) imaging in
      estimating oxygen saturation of blood (%HbO2) in the superior mesenteric vein
      (SMV) of a canine model in vivo. MATERIALS AND METHODS: MR imaging was used to
      measure the T2 of blood in samples obtained via a catheter placed in the SMV in
      seven mongrel dogs. %HbO2 was measured with a reflectance oximeter. These
      measurements were obtained at the resting state, during superior mesenteric
      artery occlusion, and after reperfusion. MR imaging and oximeter measurements
      were then compared by using linear regression analysis. RESULTS: Refocusing
      intervals (tau 180) of 12 and 24 msec were used for 17 and 18 %HbO2 measurements
      with MR imaging, respectively. With tau 180 of 12 msec, there was an excellent
      correlation between MR imaging measurements and oximeter measurements (r = .969).
      The intercept was 5.3% and the slope was 0.959. With tau 180 of 24 msec, r =
      .953, the intercept was 15.4%, and the slope was 0.817. CONCLUSION: Estimates of
      %HbO2 in the SMV with MR imaging are accurate in the range of most clinical
      interest.

PMID- 7824706
TI  - Simultaneous measurement of flow in the superior mesenteric vein and artery with
      cine phase-contrast MR imaging: value in diagnosis of chronic mesenteric
      ischemia. Work in progress.
AB  - PURPOSE: To evaluate the use of measurements of blood flow in the superior
      mesenteric vein (SMV) and superior mesenteric artery (SMA) simultaneously
      acquired with phase-contrast cine magnetic resonance (MR) imaging for diagnosing
      chronic mesenteric ischemia. MATERIALS AND METHODS: Simultaneous measurements of
      flow in the SMV and SMA were obtained in six healthy volunteers and eight
      patients with angiographically proved SMA stenosis (six asymptomatic, two
      symptomatic). Flow dynamics in both vessels were correlated with the degree of
      arterial disease seen at angiography and with the presence or absence of ischemic
      symptoms. RESULTS: Postprandial SMV and SMA flow increased substantially less in
      patients with atherosclerosis than in volunteers. Comparison of simultaneous SMV
      and SMA flow measurements provided more information about collateral flow to and
      from the mesenteric circulation than did either the SMV or SMA flow measurement
      alone. CONCLUSION: Simultaneous SMV and SMA flow measurement with cine phase
      contrast MR imaging may be useful in diagnosing and understanding chronic
      mesenteric ischemia.

PMID- 7824707
TI  - Thoracic aortic dissection: diagnosis with transesophageal echocardiography
      versus MR imaging.
AB  - PURPOSE: To compare transesophageal echocardiography (TEE) and magnetic resonance
      (MR) imaging in the diagnosis of dissection of the thoracic aorta. MATERIALS AND
      METHODS: Thirty-one consecutive patients with clinically suspected aortic
      dissection and 10 postoperative patients underwent transesophageal color Doppler
      echocardiography and MR imaging. Imaging results were compared at independent
      double-blind readings. Final diagnosis was obtained from consensual review of all
      corroborative studies. RESULTS: MR imaging depicted the intimal flap in 95% of
      aortic dissections; TEE, in 86% (P < .05). In surgical patients, the sensitivity
      of MR in detection of residual dissection was 100% versus 86% with TEE (P < .05).
      The inferior extent of the dissected lumen was seen only with MR imaging. False
      positive results occurred in two cases with TEE and in one with MR imaging.
      CONCLUSION: MR imaging is superior to TEE in the evaluation and follow-up of
      dissection of the thoracic aorta. Because the availability of MR is limited,
      however, TEE should remain the standard modality for diagnosis.

PMID- 7824708
TI  - Thrombosed dialysis grafts: comparison of treatment with transluminal angioplasty
      and surgical revision.
AB  - PURPOSE: To compare the usefulness of transluminal angioplasty coupled with
      thrombectomy versus surgical revision coupled with thrombectomy in the
      restoration and maintenance of flow in thrombosed dialysis access grafts.
      MATERIALS AND METHODS: Twenty-four patients undergoing 28 angioplasty procedures
      were retrospectively compared to 24 patients who underwent 33 surgical revisions
      with a minimum 12-month follow-up period. All patients had thrombosed upper-arm
      expanded polytetrafluoroethylene (ePTFE) grafts. RESULTS: Initial success rates
      were 88% for angioplasty and 87% for surgery. Mean primary patency for
      angioplasty and surgery was 4.6 and 3.3 months, respectively. Mean secondary
      patency for angioplasty and surgery was 5.4 and 4.5 months, respectively. These
      differences were not statistically significant. A significantly shorter hospital
      stay and lower anesthesia requirement were noted in the angioplasty group.
      CONCLUSION: Transluminal angioplasty coupled with Fogarty thrombectomy is an
      effective alternative to surgical revision for thrombosed dialysis access grafts.
      Angioplasty extends graft life, thereby preserving proximal venous outflow sites
      for future use.

PMID- 7824709
TI  - Normal pelvic lymph nodes: evaluation with CT after bipedal lymphangiography.
AB  - PURPOSE: To establish guidelines to determine the normal size of pelvic lymph
      nodes by correlating computed tomographic (CT) and lymphangiographic data.
      MATERIALS AND METHODS: Forty men in whom stage I testicular tumors were being
      treated underwent CT scanning 3-4 months after undergoing lymphangiography. The
      site, size, and number of nodes at CT scanning were documented. Maximum short
      axis diameter (MSAD) was measured at four anatomic sites in the pelvis. Results
      were analyzed with histograms, and median and percentile values were calculated.
      RESULTS: There were 187 nodes measured in 27 men before lymphangiography. There
      were 1,801 nodes measured in 40 patients after lymphangiography. Median MSAD
      values at CT after lymphangiography were 5 mm or less; fewer than 2% of nodes had
      an MSAD greater than 10 mm. CONCLUSION: Almost all normal pelvic nodes are less
      than 10 mm MSAD, depending on the site. The low sensitivity of CT in depicting
      metastases to the pelvic lymph nodes might be improved by adopting upper limits
      of normal that reflect this size.

PMID- 7824710
TI  - Use of low-osmolar agents and premedication to reduce the frequency of adverse
      reactions to radiographic contrast media: a survey of the Society of
      Uroradiology.
AB  - PURPOSE: To assess the decisions made by uroradiologists regarding choice of type
      of intravenous contrast material (low-osmolar contrast media [LOCM] vs
      conventional ionic agents) and frequency of use of corticosteroid prophylaxis.
      MATERIALS AND METHODS: A questionnaire was mailed to 158 members of the Society
      of Uroradiology. There were 108 responses received, yielding a response rate of
      68%. Results from 76 represented institutions were tabulated. RESULTS: Most
      respondents practice at institutions in which LOCM are used selectively rather
      than universally. Corticosteroid prophylaxis in patients at risk is used with
      similar frequency at both types of institutions. There is considerable diversity
      in pretreatment regimens (ie, type and dose of corticosteroid used). Although
      antihistamines are used by many uroradiologists (almost always in conjunction
      with corticosteroids), H2 receptor antagonists are used at only a few
      institutions. CONCLUSION: At institutions in which LOCM are used selectively, the
      majority of respondents use LOCM quite liberally, with most choosing these agents
      in patients at risk. Corticosteroid prophylaxis is widely used by respondents.
      There is much variation in the type of pretreatment regimen and its use in
      specific clinical settings.

PMID- 7824711
TI  - Professional and business characteristics of radiology groups in the United
      States: 1992.
AB  - PURPOSE: In response to requests, to present information on the professional and
      business characteristics of radiology groups. MATERIALS AND METHODS: The American
      College of Radiology surveyed a stratified random sample of radiology groups,
      defining radiology group as any practice with two or more radiologists or
      radiation oncologists, including academic departments, units in multispecialty
      groups, and staff of government facilities. The 465 responses (69% response rate)
      were weighted so the data show what findings would have been if all radiology
      groups in the country had responded. RESULTS: ACR professional standards are
      widely used, particularly those for mammography and radiation oncology. Seventy
      eight percent of groups required continuing training of their technologists. On
      average, groups required 2.7 years for new members to become full partners. The
      average group gave full-time radiologists 11 holidays, 26 vacation days, and 11
      days for continuing medical education each year. On average, groups collected 71%
      of total billings. Net collections (after "allowances" for Blue Shield, Medicare,
      and other payers are deducted from billings) averaged 86%; half of services were
      provided by groups with net collection rates of 90% or more. CONCLUSION: In
      general, changes since 1989 (when the previous Group Practice Survey was
      conducted) were small.

PMID- 7824712
TI  - Demographic characteristics of physicists who evaluate mammographic units.
AB  - PURPOSE: To determine whether there will be an adequate number of physicists to
      meet the 1996 American College of Radiology (ACR) Mammography Accreditation
      Program requirements and assess the qualifications of physicists available to
      evaluate mammography units as required by the federal Mammography Quality
      Standards Act of 1992. MATERIALS AND METHODS: A 21-question survey prepared by
      the ACR was sent to most medical physicists who perform evaluations of
      mammographic units. Replies were received from 1,011 individuals. RESULTS: Survey
      results are based on the replies of 824 individuals who indicated a willingness
      to perform evaluations in the future. In 1996, there will be approximately 510
      certified physicists to evaluate an estimated 14,000 mammography units in the
      United States. CONCLUSION: A sufficient number of certified diagnostic medical
      physicists will be available to provide required annual performance evaluations
      of all mammography units in the United States only if the number of units
      evaluated per physicist increases substantially over current levels.

PMID- 7824713
TI  - Stereotaxic core biopsy of breast carcinoma: accuracy at predicting invasion.
AB  - PURPOSE: To assess the accuracy with which stereotaxic core biopsy of breast
      carcinoma predicts the presence of invasion. MATERIALS AND METHODS: Stereotaxic
      core biopsy was performed in 63 breast carcinomas in 59 patients in the prone
      position. All patients subsequently underwent surgery. Histopathologic results of
      stereotaxic core biopsy and surgery were correlated. RESULTS: Results of
      stereotaxic core biopsy and surgery were concordant in 58 (92%) of the 63 cases,
      yielding invasive carcinoma in 46 cases and ductal carcinoma in situ (DCIS) in 12
      cases. Results were discordant in five cases (8%), including three cases for
      which stereotaxic core biopsy results indicated DCIS but surgery yielded invasive
      ductal carcinoma. The positive predictive value of stereotaxic core biopsy for
      the presence of invasion was 98% (47 of 48 cases) and the negative predictive
      value was 80% (12 of 15 cases). CONCLUSION: Stereotaxic core biopsy of breast
      carcinoma can help confirm invasion with high accuracy but cannot reliably
      indicate the absence of tumor invasion when only DCIS is found.

PMID- 7824714
TI  - Pressures in a simulated breast subjected to compression forces comparable to
      those of mammography. Work in Progress.
AB  - PURPOSE: To determine the magnitude and distribution of pressures in breast
      models subjected to mammographic compression forces. MATERIALS AND METHODS: A
      vinyl-wrapped, unleavened-bread-dough breast model was compressed. Pressures in
      the dough models were measured with a strain gauge connected to a water-filled
      sensor. RESULTS: Under broad compression, pressures were uniform (range, 2.76
      22.06 kPa [0.4-3.2 psi]). Spot compression increased pressures by as much as 60%.
      Pressures dropped sharply outside of paddle margins. No pressure differentials
      were found near small, deep simulated masses. The pressure of large masses
      increased by 50% when subjected to full compression force. Vigorous digital
      palpation resulted in a pressure of more than 41.40 kPa (6 psi). CONCLUSION:
      General pressures were mild and uniform. Internal pressures varied inversely with
      the area to which force was applied. Pressure dissemination was restricted by the
      cohesive binder and allowed zones of greater pressure to form directly under the
      applied force. The surrounding matrix disseminated pressure and protected small
      masses; large masses, bearing the force of the paddle, were exposed to greater
      pressure. Digital palpation administered high pressures.

PMID- 7824715
TI  - Latent image fading in screen-film mammography: lack of clinical relevance for
      batch-processed films.
AB  - PURPOSE: To assess the clinical relevance of latent image fading due to time
      delays in batch-processed screening mammograms. MATERIALS AND METHODS: Results of
      all 66,667 mammographic examinations performed in a mobile van since April 1985
      were retrospectively analyzed. Film was routinely batch processed at the end of
      the workday. The rate of repeat examination due to poor image quality, rate of
      abnormal interpretation, and rate of cancer detection were studied. RESULTS:
      Essentially no differences were found in the rates at which repeat examination
      was necessary, abnormal interpretations were made, or breast cancers were
      detected when examinations performed at the beginning, middle, and end of the
      workday were compared (time delays in film processing ranged from 15 minutes to 8
      hours). CONCLUSION: Latent image fading is not accompanied by clinically relevant
      impairment of results if films are processed at the end of the workday. Latent
      image fading should not deter the use of batch-film processing.

PMID- 7824716
TI  - Pulmonary nodules: CT evaluation of enhancement with iodinated contrast material.
AB  - PURPOSE: To determine if the degree of enhancement of pulmonary nodules is
      directly related to the likelihood of malignancy and to the vascularity of the
      nodule. MATERIALS AND METHODS: Uncalcified 6-40-mm-diameter pulmonary nodules
      were studied in 163 patients with malignant neoplasm (n = 111), granuloma (n =
      43), and benign neoplasm (n = 9). Serial thin-section computed tomography (CT)
      was performed before and after injection of 100 mL of nonionic contrast material
      at 2 mL/sec. The maximum level of enhancement was recorded. Eighteen histologic
      specimens were graded after vascular staining. RESULTS: Malignant neoplasms
      enhanced (median, 40.0 HU; range, 20-108 HU) significantly more than granulomas
      and benign neoplasms (median, 12.0 HU; range, -4 to 58 HU) (P < .001). With 20 HU
      as the threshold for a positive test, sensitivity was 100%; specificity, 76.9%;
      positive predictive value, 90.2%; negative predictive value, 100%; and accuracy,
      92.6% (prevalence of malignancy, 68.1%). Degree of enhancement was significantly
      related to amount of central vascular staining (P = .003). CONCLUSION:
      Enhancement is an indicator of malignancy and vascularity.

PMID- 7824717
TI  - Solitary pulmonary nodule: preliminary study of evaluation with incremental
      dynamic CT.
AB  - PURPOSE: To use incremental dynamic computed tomography (CT) to evaluate solitary
      pulmonary nodules (SPNs). MATERIALS AND METHODS: Thirty-two adult patients with
      SPNs less than 3 cm in diameter had 18 primary lung cancers, 10 tuberculomas, and
      four hamartomas. The CT numbers of the inner area of the nodule were calculated
      before and 30 seconds, 2 minutes, and 5 minutes after administration of contrast
      material. RESULTS: All lung cancers and one of four hamartomas showed
      significantly greater enhancement (P < .0001) than benign SPNs, which did not
      show enhancement (except for one hamartoma). All lung cancers and one of four
      hamartomas showed complete enhancement, one hamartoma showed peripheral
      enhancement, two hamartomas and eight of 10 tuberculomas showed capsular
      enhancement, and two tuberculomas showed no enhancement. CONCLUSION: Maximum
      attenuation of 20-60 HU appears to be a good predictor of malignancy.

PMID- 7824719
TI  - My experience as an RSNA international visiting professor to Monterrey, Mexico.

PMID- 7824718
TI  - Clinical evaluation of pulmonary nodules with single-exposure dual-energy
      subtraction chest radiography with an iterative noise-reduction algorithm.
AB  - PURPOSE: To compare the clinical usefulness of the single-exposure dual-energy
      subtraction method with an iterative noise-reduction algorithm. MATERIALS AND
      METHODS: Fourteen radiologists read three sets of images from 44 patients:
      original computed radiographic images only, original computed radiographic images
      plus conventional bone-subtracted images, and original computed radiographic
      images plus iterative noise-reduced bone-subtracted images. Twenty-two patients
      had one or more (maximum, five) pulmonary nodules; 22 had no pulmonary nodules.
      Observer performance was evaluated by means of calculation of the average area
      under the alternative free-response receiver operating characteristic curves
      (A1). RESULTS: Compared with the original computed radiographic image only,
      detection of nodules was significantly better with both the original computed
      radiographic image plus iterative bone-subtracted image (A1 = 0.72 +/- 0.02 and
      0.66 +/- 0.02, respectively; P = .01) and the original computed radiographic
      image plus conventional bone-subtracted image (A1 = 0.66 +/- 0.02 and 0.61 +/-
      0.01, respectively; P = .03). CONCLUSION: The iterative noise-reduction algorithm
      is superior to conventional methods in detection of pulmonary nodules.

PMID- 7824720
TI  - Pulmonary tuberculosis and Mycobacterium avium-intracellulare: a comparison of CT
      findings.
AB  - PURPOSE: To compare the computed tomographic (CT) findings of tuberculosis and
      Mycobacterium avium-intracellulare (MAI) infection in immunocompetent patients.
      MATERIALS AND METHODS: Seventy-seven consecutive immunocompetent patients with
      culture-proved pulmonary mycobacterial infection (45 with pulmonary tuberculosis,
      32 with MAI) underwent thin-section CT. CT scans were randomized and reviewed by
      two observers; decisions were reached by consensus. RESULTS: Micronodules,
      consolidation, and cavity formation in the lung were seen with similar frequency
      in pulmonary tuberculosis and MAI cases. Twenty-three patients (51%) with
      tuberculosis and four patients (12%) with MAI had interlobular septal thickening
      (P < .001). Twelve patients (27%) with tuberculosis and 30 patients (94%) with
      MAI had bronchiectasis (P < .001). Bronchiectasis was seen in a mean of 4.6 +/-
      1.8 and 1.8 +/- 1.6 lobes (+/- standard deviation) in each patient with MAI and
      with tuberculosis, respectively (P < .01). CONCLUSION: Although CT findings of
      pulmonary tuberculosis and MAI are similar, interlobular septal thickening is
      more common in patients with tuberculosis and bronchiectasis is more common and
      more extensive in patients with MAI.

PMID- 7824721
TI  - CT assessment of bronchi in sarcoidosis: endoscopic and pathologic correlations.
AB  - PURPOSE: To evaluate the computed tomographic (CT) appearance of bronchi in
      patients with sarcoidosis and to correlate CT, endoscopy, and bronchial biopsy
      findings. MATERIALS AND METHODS: Sixty patients with sarcoidosis underwent CT and
      tracheobronchial endoscopy. CT findings of abnormalities of the bronchial walls
      and lumina were compared with endoscopic and biopsy findings. RESULTS: CT scans
      showed bronchial abnormalities in 39 patients (65%). CT and endoscopic findings
      were concordant in only 35 cases. However, CT showed abnormal lumina in 14
      patients and endoscopy showed mucosal thickening in 12 of these 14 patients. CT
      findings of bronchial abnormalities were associated with the presence of
      bronchial granulomas (P < .0001). CT scans showed that, of the 37 patients with
      biopsy results of granulomatosis, 84% had thickened bronchial walls and 35% had
      luminal abnormalities. Eight CT findings were false-positive, and six were false
      negative for the presence of granulomas. CONCLUSION: Bronchial involvement in
      sarcoidosis was detected at CT in 65% of cases. CT can help predict whether
      bronchial granulomas will be found in cases of sarcoidosis.

PMID- 7824722
TI  - Triple-head SPECT with 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG): initial
      evaluation in oncology and comparison with FDG PET.
AB  - PURPOSE: In patients with cancer, performance was assessed of a commercially
      available triple-head gamma camera fitted with ultra-high energy parallel-hole
      collimators performing single photon emission computed tomography (SPECT) with 2
      [fluorine-18]fluoro-2-deoxy-D-glucose (FDG). Results were compared with those of
      positron emission tomography (PET) with FDG. MATERIALS AND METHODS: Performance
      characteristics were first determined in phantom studies for FDG PET and triple
      head gamma camera SPECT systems. In 13 patients with malignancies, FDG PET was
      followed by SPECT of the same region, and imaging results were independently
      assessed. RESULTS: Sensitivity of the PET and SPECT systems was 58.3
      counts/MBq/min and 4.5 counts/MBq/min, respectively. Reconstructed spatial
      resolution was approximately 7 mm for PET and 20 mm for SPECT. All known cancer
      foci were detected at PET. SPECT depicted 11 of the 22 lesions detected at PET,
      but only five of the 14 lesions less than 3 cm in diameter. CONCLUSION: FDG SPECT
      performed with a specially collimated triple-head gamma camera depicted some
      cancers but had an unacceptably low sensitivity compared with PET for lesions
      less than 3 cm in diameter. PET is preferable for detecting small cancers.

PMID- 7824723
TI  - Comparison of breath-hold fast spin-echo and conventional spin-echo pulse
      sequences for T2-weighted MR imaging of liver lesions.
AB  - PURPOSE: To evaluate a breath-hold fast spin-echo (SE) technique for T2-weighted
      magnetic resonance (MR) imaging of liver lesions. MATERIALS AND METHODS: A fast
      SE technique was developed that enabled six sections to be imaged per 16-second
      breath hold with a single echo. Resulting images were compared with those
      obtained with the first echo of a conventional dual-echo T2-weighted SE sequence
      (16 minutes 55 seconds for 18 sections). Thirty-one patients with malignant focal
      hepatic lesions were studied prospectively. The images were compared
      quantitatively and qualitatively. RESULTS: Quantitatively, the contrast and
      contrast-to-noise ratios for the fast SE images were 20% +/- 5 and 19% +/- 8
      greater, respectively, than those for the conventional T2-weighted SE images of
      the 54 representative lesions. Qualitatively, fast SE images had less image
      artifact, enabled comparable or better lesion sizing, and greatly improved
      depiction of extrahepatic structures compared with conventional T2-weighted SE
      images. CONCLUSION: The fast SE technique with breath holding provides
      diagnostically useful liver images in a greatly decreased acquisition time.

PMID- 7824724
TI  - T2-weighted breath-hold MR imaging of the liver at 1.5 T: results with a three
      dimensional steady-state free precession sequence in 87 patients.
AB  - PURPOSE: To evaluate a fast three-dimensional (3D) sequence that permits the
      acquisition of 16 T2-weighted images within a 29-second breath hold for magnetic
      resonance (MR) imaging of the liver. MATERIALS AND METHODS: Eighty-seven patients
      with focal liver lesions were examined at 1.5 T by using a 3D reversed fast
      imaging with steady-state precession (PSIF) sequence at flip angles of 15
      degrees, 30 degrees, and 70 degrees and a T2-weighted spin-echo (SE) sequence.
      Quantitative and qualitative image analysis was performed. RESULTS: Contrast and
      signal difference-to-noise ratios were 56% and 33% (liver-spleen) and 76% and 68%
      (liver-tumor), respectively, with the 3D-PSIF sequence compared with the T2
      weighted SE sequence. With 3D-PSIF, overall image quality was poorer than that of
      the T2-weighted SE sequence at flip angles of 15 degrees but was similar at 30
      degrees and 70 degrees. At low flip angles (15 degrees and 30 degrees) all lesion
      types were hyperintense. At a flip angle of 70 degrees, it was predominantly
      cysts and hemangiomas that showed high signal intensity. With the 3D-PSIF
      sequence, intrahepatic vessels are void of signal and can be better distinguished
      from small liver lesions compared with the flow-compensated T2-weighted SE
      sequence. CONCLUSION: The fast 3D-PSIF sequence is a valuable addition to MR
      imaging of the liver.

PMID- 7824725
TI  - Giant ulcers of the esophagus in patients with human immunodeficiency virus:
      clinical, radiographic, and pathologic findings.
AB  - PURPOSE: To determine the causes of giant esophageal ulcers in patients with
      human immunodeficiency virus (HIV) and whether clinical or radiographic criteria
      can be used to differentiate the infections that cause these ulcers. MATERIALS
      AND METHODS: From January 1990 through December 1993, giant esophageal ulcers ( >
      or = 1 cm in diameter) were found in 21 HIV-positive patients (19 men and two
      women 23-66 years of age; mean, 39 years). The radiographic findings were
      reviewed and correlated with clinical, endoscopic, and pathologic findings.
      RESULTS: In 16 patients, the ulcers were caused by HIV, in three by
      cytomegalovirus (CMV), and in two by CMV and HIV. The clinical and radiographic
      findings were the same for the two types of ulcers. However, HIV ulcers responded
      to treatment with steroids, and CMV ulcers responded to treatment with
      ganciclovir. CONCLUSION: It is not possible to differentiate HIV from CMV ulcers
      on the basis of clinical or radiographic criteria; thus, endoscopy is necessary
      for a definitive diagnosis.

PMID- 7824726
TI  - Uneven fatty replacement of the pancreas: evaluation with CT.
AB  - PURPOSE: To determine the computed tomographic (CT) features of uneven fatty
      replacement of the pancreas and clarify their radiologic and clinical importance.
      MATERIALS AND METHODS: CT scans from 80 patients with uneven fatty replacement of
      the pancreas were reviewed. Uneven fatty replacement of the pancreas was
      classified into two types. In type 1, the posterior aspect of the head of the
      pancreas was spared from intense fatty replacement. In type 2, the focal area
      around the common bile duct (CBD) was spared from fatty replacement. Each type
      was divided into two subgroups on the basis of whether the body and tail of the
      pancreas showed intense fatty replacement (type a = negative for intense fatty
      replacement, type b = positive for intense fatty replacement). Findings from
      endoscopic retrograde cholangiopancreatography performed in five patients,
      histopathologic examination in one patient, and clinical examination in all 80
      patients were also evaluated. RESULTS: Twenty-eight patients (35%) had type 1a
      replacement, 29 (36%) had type 1b replacement, nine (11%) had type 2a
      replacement, and 14 (18%) had type 2b replacement. In all patients, the anterior
      aspect of the head of the pancreas showed distinctly lower attenuation at CT.
      CONCLUSION: Fatty replacement is more severe in the anterior aspect of the head
      of the pancreas. The posterior aspect of the head of the pancreas and the area
      around the CBD tended to be spared.

PMID- 7824727
TI  - Carotid artery stenosis: clinical efficacy of MR phase-contrast flow
      quantification as an adjunct to MR angiography.
AB  - PURPOSE: To assess the utility of magnetic resonance (MR) flow quantification in
      the evaluation of suspected carotid artery stenosis. MATERIALS AND METHODS: Fifty
      five patients referred for angiography and 10 healthy volunteers underwent
      Doppler ultrasound, three-dimensional time-of-flight MR angiography, and MR phase
      contrast flow quantification to measure peak systolic velocity (PSV) and
      volumetric flow rate (VFR) in the common and internal carotid arteries distal to
      the stenosis. RESULTS: PSV and VFR were significantly lower in the severely (> or
      = 70%) stenosed internal carotid arteries (P < .05). The VFR ratio (internal
      carotid artery-common carotid artery) achieved 91% overall accuracy for detection
      of severe stenosis. Combination of flow data with results of MR angiography
      yielded sensitivity of 100% (95% confidence interval, 78%-100%) with a modest
      loss in specificity. Doppler and MR measurements of PSV in the common carotid
      artery showed significant correlation: volunteers, r = .73; patients, r = .64.
      CONCLUSION: MR flow quantification provides information about the hemodynamic
      significance of carotid stenosis. As an adjunct to MR angiography, it may be
      useful in enabling differentiation of occlusions from critical stenoses.

PMID- 7824728
TI  - Periventricular venous collagenosis: association with leukoaraiosis.
AB  - PURPOSE: To investigate the association between an age-related degenerative
      disease of subependymal veins and leukoaraiosis. MATERIALS AND METHODS: Brains
      obtained at autopsy from 22 patients (average age, 73.2 years; range, 25-95
      years) were examined with magnetic resonance (MR) imaging and neuropathologic
      methods with alkaline phosphatase microvascular staining. The degrees of
      leukoaraiosis shown on MR images and of deep venous occlusion were scored
      independently and results compared with logistic regression analysis. RESULTS:
      Noninflammatory collagenous thickening of venous walls resulting in severe
      periventricular venous stenosis was found in 13 (65%) of 20 patients over 60
      years old. Advanced leukoaraiosis was found in 10 (77%) of these 13 patients.
      Greater venous disease was associated with more severe leukoaraiosis. CONCLUSION:
      Periventricular venous collagenosis, a commonly observed and previously ignored
      degenerative disease of elderly humans, is strongly associated with
      leukoaraiosis. Stenosis or occlusion of deep cerebral veins may promote
      development of leukoaraiosis.

PMID- 7824729
TI  - Enhancement of the intracranial arterial wall at MR imaging: relationship to
      cerebral atherosclerosis.
AB  - PURPOSE: To investigate the relationship between intracranial arterial wall
      enhancement and atherosclerosis. MATERIALS AND METHODS: Intracranial vertebral
      arteries of 30 patients and carotid arteries of 62 patients were studied with
      spin-echo magnetic resonance imaging with contrast enhancement and spatial
      presaturation. Arterial wall enhancement was graded as follows: stage 1, no
      substantial enhancement; stage 2, faint or thin area of enhancement; stage 3,
      definite and thick area of enhancement. RESULTS: In vertebral arteries, stage 3
      enhancement was seen in 11 patients (mean age, 73.7 years) and stage 1 in eight
      (mean age, 56.4 years). In carotid arteries, stage 3 enhancement was seen in 13
      patients (mean age, 71.0 years) and stage 1 in 21 patients (mean age, 39.0
      years). In both arteries, stage was well correlated with age (P < .05).
      CONCLUSION: Arterial wall enhancement is related to aging and is probably due to
      neovascularity in association with atherosclerotic plaques. This finding may
      permit assessment of intracranial atherosclerosis and other vascular diseases.

PMID- 7824730
TI  - Prenatally detected fetal myelomeningocele: is karyotype analysis warranted?
AB  - PURPOSE: To determine the prevalence of karyotype abnormalities in fetuses with
      prenatally detected spina bifida and evaluate the ability of prenatal sonography
      to enable prediction of chromosomal abnormalities. MATERIALS AND METHODS:
      Sonograms from 63 fetuses with prenatally detected spina bifida were reviewed,
      and associated sonographic abnormalities were recorded. Sonographic findings were
      correlated with autopsy or clinical findings when possible. RESULTS: Associated
      sonographic abnormalities were present in 15 (24%) of fetuses with spina bifida.
      Among 52 fetuses with known karyotypes, the prevalence of chromosome
      abnormalities was 17%. Karyotype abnormalities included trisomy 18, trisomy 13,
      triploidy, and translocation. Twenty-two percent of chromosomally abnormal
      fetuses had sonographically isolated spina bifida. CONCLUSION: Prenatal
      sonography can help predict most karyotypically abnormal fetuses with spina
      bifida, but approximately 20% will be missed with this technique alone in the
      second trimester. The authors believe cytogenetic analysis is justified in the
      setting of prenatally detected spina bifida.

PMID- 7824731
TI  - Neoplasms in a pediatric population: 2-[F-18]-fluoro-2-deoxy-D-glucose PET
      studies.
AB  - PURPOSE: To assess the uptake of 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG)
      in common and uncommon tumors in children and to develop a method for performing
      positron emission tomography (PET) studies in children with malignant neoplasms.
      MATERIALS AND METHODS: Twenty-two pediatric patients with known or suspected
      malignancies (27 scans) underwent FDG PET. Tumor uptake of FDG was measured on
      PET scans. RESULTS: Tumor uptake of FDG was detected in 17 of 21 patients with
      malignant disease. Neuroblastomas and their metastases (including those that did
      not absorb metaiodobenzylguanidine) intensely accumulated FDG. In a patient with
      Ewing sarcoma, FDG PET showed two foci of metastatic disease not evident on bone
      scans. In two patients, PET showed that large areas of the tumor were necrotic.
      CONCLUSION: FDG PET is feasible, is useful in the study of tumors in children,
      and may provide unique, clinically important information.

PMID- 7824732
TI  - Congenital urethroperineal fistula.
AB  - PURPOSE: To characterize the radiographic appearances of congenital
      urethroperineal fistula and to distinguish it from urethral duplication of the
      hypospadiac type. MATERIALS AND METHODS: The authors examined four patients with
      congenital urethroperineal fistula in whom radiographic examinations were
      performed to define the pathologic anatomy. RESULTS: Congenital urethroperineal
      fistula mimics the hypospadiac form of urethral duplication, except the normally
      positioned dorsal channel is the normal urethra. Patients with congenital
      urethroperineal fistula have normal micturition. Both a normal dorsal penile
      urethra and a ventral urethroperineal fistula can be observed during radiographic
      and cystoscopic examination. The dorsal urethra is the functionally normal
      channel. Excision of the ventral channel is simple and curative. This contrasts
      starkly with congenital urethral duplication of the hypospadiac type, where
      excision of the ventral channel may be catastrophic. CONCLUSION: Although it
      resembles the hypospadiac form of urethral duplication, congenital
      urethroperineal fistula should be classified as a separate entity.

PMID- 7824733
TI  - MR velocity mapping of tricuspid flow in healthy children and in patients who
      have undergone Mustard or Senning repair.
AB  - PURPOSE: To determine the feasibility and accuracy of measuring tricuspid volume
      flow with magnetic resonance (MR) velocity mapping in healthy children and in
      patients after a Mustard or Senning repair. MATERIALS AND METHODS: MR studies
      were performed in 14 healthy children (mean age, 12 years +/- 3) and in 12
      patients (mean age, 17 years +/- 5) late after a Mustard or Senning repair. MR
      measurements of tricuspid volume flow were validated against right ventricular
      stroke volumes measured tomographically. Diastolic filling parameters were
      derived from the flow measurements. RESULTS: Tricuspid volume flow and right
      ventricular stroke volume showed close agreement in the healthy children (r =
      .98) and in the patients (r = .94). Children after Senning repair, compared with
      healthy children, showed a delayed and higher peak tricuspid flow rate during
      early filling and a lower peak flow rate during atrial contraction (P < .05).
      CONCLUSION: MR measurement of tricuspid flow is feasible and accurate in healthy
      children and in patients after a Mustard or Senning operation, who often
      demonstrate abnormal tricuspid flow patterns.

PMID- 7824734
TI  - John Caffey and his contributions to radiology.

PMID- 7824735
TI  - Acute pes anserine bursitis: MR imaging.
AB  - PURPOSE: To determine the magnetic resonance (MR) imaging appearance of acute pes
      anserine bursitis. MATERIALS AND METHODS: Four patients (aged 40-50 years) with
      presumed internal derangements of the knee underwent MR imaging; at that time,
      collections of fluid were found in the pes anserine bursa, but no other
      abnormalities were noted. RESULTS: Pes anserine bursitis was clinically diagnosed
      in all four patients when MR findings and physical examination findings were
      correlated. CONCLUSION: Pes anserine bursitis has a characteristic MR appearance
      of fluid beneath the tendons of the pes anserinus at the medical aspect of the
      tibia near the joint line. Pes anserine bursitis can clinically mimic an internal
      derangement of the knee, which can result in the performance of unnecessary
      arthroscopy. MR imaging can be useful in diagnosing pes anserine bursitis and
      obviating surgery.

PMID- 7824736
TI  - Early sacroiliitis in patients with spondyloarthropathy: evaluation with dynamic
      gadolinium-enhanced MR imaging.
AB  - PURPOSE: To investigate the diagnostic value of gadolinium-enhanced magnetic
      resonance (MR) imaging in the detection of early sacroiliitis. MATERIALS AND
      METHODS: Of 125 patients with back pain, 72 had inflammatory back pain and had a
      diagnosis of spondylarthropathy; the other 53 patients had other mostly
      mechanical causes of back pain and served as the control group. The 72 patients
      with spondyloarthropathy were further subdivided into two groups according to
      established radiographic criteria for ankylosing spondylitis. While group 2
      patients (n = 36) with a diagnosis of ankylosing spondylitis had definite
      radiographic changes in the sacroiliac joints, group 1 patients (n = 36) with
      undifferentiated spondylarthropathy had no such findings. RESULTS: While no
      contrast enhancement was found in normal sacroiliac joints, significantly
      different degrees of enhancement (P < .05) related to the patients' degree of
      pain were clearly detected in both groups of patients with spondyloarthropathy.
      Contrary to the mostly normal findings with precontrast MR imaging and with
      radiography, dynamic MR imaging revealed small erosions (< 1 mm) in 47 (72%) of
      the 65 inflamed joints in group 1 and juxtaarticular osteitis in 53 (82%).
      CONCLUSION: Contrast-enhanced MR imaging allows detection of sacroiliitis in
      early stages.

PMID- 7824737
TI  - Female pelvic bone marrow: serial MR imaging before, during, and after radiation
      therapy.
AB  - PURPOSE: To study early changes in irradiated pelvic and adjacent nonirradiated
      bone marrow with T1-weighted magnetic resonance (MR) and short inversion time
      inversion-recovery (STIR) imaging. MATERIALS AND METHODS: The bone marrow of 31
      women with advanced cervical carcinoma was studied in 161 MR examinations before,
      during, and 7 weeks after radiation therapy. Two radiologists visually evaluated
      the marrow signal intensity (MSI) on T1-weighted and STIR images. RESULTS:
      Changes in irradiated and adjacent nonirradiated marrow were shown on T1-weighted
      images in 31 (100%) and 18 (58%) of the 31 patients, respectively. MSI changes on
      images were observed as early as 8 days after the start of radiation therapy and
      occurred more frequently in irradiated than in adjacent nonirradiated marrow. In
      the irradiated regions, a complete fatty marrow was seen on T1-weighted images
      obtained 6-8 weeks after the start of radiation therapy in 28 (90%) of the 31
      patients. CONCLUSION: T1-weighted and STIR images obtained during and soon after
      radiation therapy complement each other in showing changes in bone marrow.

PMID- 7824738
TI  - Adnexal masses: accuracy of characterization with transvaginal US and precontrast
      and postcontrast MR imaging.
AB  - PURPOSE: To determine the accuracy of transvaginal ultrasound (TVUS) and of
      precontrast and contrast material-enhanced magnetic resonance (MR) imaging in the
      differentiation of adnexal masses. MATERIALS AND METHODS: Five blinded readers
      analyzed images of 80 masses in 72 patients. MR and TVUS images were interpreted
      in separate sessions. Findings were confirmed at surgery or laparoscopy. RESULTS:
      Higher diagnostic accuracy was attained with MR imaging in mature cystic
      teratomas and endometriomas. However, better accuracy was achieved with contrast
      enhanced MR imaging and TVUS in simple cysts, cystadenomas, and malignant tumors
      because internal details could be visualized. Receiver operating characteristic
      study indicated that observer confidence was significantly higher with contrast
      enhanced MR imaging than with precontrast MR imaging (P = .011) or TVUS (P =
      .002) in the differentiation of benign and malignant masses. CONCLUSION: Contrast
      enhanced MR imaging is superior to precontrast MR and TVUS imaging in the
      characterization and differentiation of adnexal masses.

PMID- 7824740
TI  - US-guided core biopsy of the breast with a coaxial system.
AB  - From July 1993 through June 1994, the authors performed 42 ultrasound (US)-guided
      core biopsies with use of a coaxial technique in which a 14- or 15-gauge core
      biopsy needle was passed through a 12-gauge introducer needle. This technique
      proved to be effective in all 42 biopsies. Use of the coaxial technique decreased
      the procedure time necessary for US-guided core biopsy and may be less traumatic
      than the standard core biopsy technique.

PMID- 7824739
TI  - Clinical stage I endometrial carcinoma: pitfalls in preoperative assessment with
      MR imaging. Work in progress.
AB  - PURPOSE: To identify potential pitfalls in using magnetic resonance (MR) imaging
      to determine the depth of myometrial invasion in patients with clinical stage I
      endometrial carcinoma. MATERIALS AND METHODS: Forty women with clinical stage I
      endometrial carcinoma underwent preoperative pelvic MR imaging. Uterine length,
      tumor signal intensity, appearance of the junctional zone, presence of large
      polypoid tumors, leiomyomata, and congenital uterine anomalies were analyzed.
      Univariate logistic-regression analysis was performed to identify associations
      between incorrect MR staging and these variables. RESULTS: MR staging of IA, IB,
      and IC disease was 55% accurate (22 of 40 cases); MR differentiation of deep
      myometrial invasion (stage IC) from superficial disease (stages IA and IB) was
      78% accurate (31 of 40 cases). Older age (P = .025), presence of polypoid tumors
      (P = .025), and difficulty in pathologic staging (P < .005) were significantly
      associated with incorrect MR assessment. CONCLUSION: When present, large polypoid
      tumors, leiomyomata, congenital anomalies, small uteri, and indistinct zonal
      anatomy may make it difficult to assess myometrial invasion at MR imaging.

PMID- 7824741
TI  - Three-dimensional modeling of the oropharynx during swallowing.
AB  - The mechanical actions of swallowing in one volunteer were modeled in three
      dimensions. Biplane fluoroscopy and dynamic ultrafast computed tomography of
      adjacent levels of the pharynx were performed during swallows of liquid.
      Synchronized posteroanterior, lateral, and cross-sectional images were scanned
      and aligned in three dimensions with graphics-animation software. Modeling the
      oropharyngeal swallow helps analysis and visualization of the mechanics of
      swallowing, dysphagia, and compensatory therapeutic strategies.

PMID- 7824742
TI  - Credentialing of crossover privileges in fluoroscopy for nonradiologists.

PMID- 7824743
TI  - MR angiography of the portal venous system.

PMID- 7824744
TI  - Pregnancy bias in radiology.

PMID- 7824745
TI  - Difficulty of judging retrospectively whether a diagnosis has been "missed".

PMID- 7824746
TI  - Genitourinary radiology.

PMID- 7824747
TI  - Abdominal-gastrointestinal radiology.

PMID- 7824748
TI  - Musculoskeletal radiology.

PMID- 7824749
TI  - Nuclear medicine.

PMID- 7824750
TI  - Pediatric radiology.

PMID- 7824751
TI  - Head and neck radiology.

PMID- 7824752
TI  - Computer applications and digital imaging.

PMID- 7824753
TI  - Oncology/radiation therapy.

PMID- 7824754
TI  - Ultrasonography.

PMID- 7824755
TI  - Neuroendocrine tests in depressive stroke patients.
AB  - 1. In the present study 63 stroke patients and 23 control patients participated.
      The presence and degree of depression was defined by the Hamilton Rating Scale
      for Depression and the Research Diagnostic Criteria. 2. The TRH stimulation test
      was performed in all the patients. 3. No difference in Delta Max TSH was found
      between stroke patients and control patients. 4. No difference in Delta Max TSH
      was found between patients with the lesion in the right or left hemisphere. 5. No
      correlation was found between the frequency of blunted response to the TRH
      stimulation test and the presence of depression. 6. No difference in Delta Max
      TSH was found between suppressors and non-suppressors to the DST.

PMID- 7824756
TI  - The effect of age on plasma level of setiptiline maleate in depressed patients.
AB  - 1. Setiptiline maleate (SPT) was administered orally to 45 subjects aged 22-86
      years and steady state plasma levels were determined by mass fragment
      chromatography (GC-MF) to examine the effect of aging on those values. 2. There
      was a significant correlation between the plasma levels and daily dose. However,
      there was a wide interindividual variability. 3. Dose-corrected plasma level (DC
      PL), or values corrected by dividing the plasma level by daily dose/body weight,
      was used as the systemic drug clearance parameter. 4. DC-PL was compared among 7
      age groups of the subjects distributed in 10-year-intervals. DC-PL showed no
      difference among groups of subjects between the > 29 years bracket to the 70
      years bracket, but showed significantly higher values in those in the > 80
      bracket compared to all age groups and subjects in the < 79 bracket. 5. There was
      a significant correlation between the age of patients and DC-PL according to
      polynomial response curve analysis. Regression analysis yielded the equation y = 
      52.72 + 7.05 x -0.17 x2 + 0.01 x3 (n = 45, r = 0.49, p < 0.01).

PMID- 7824757
TI  - Serotonin and impulsive/aggressive behavior in cocaine dependent subjects.
AB  - 1. 10 male cocaine dependent patients and 10 sex matched controls were
      administered several behavioral measures of aggression including the Buss-Durkee
      Hostility Inventory, and The Brown-Goodwin Life History of Aggression. 2. All
      subjects were also administered a buspirone neuroendocrine challenge as a measure
      of serotonin function. 3. The cocaine dependent subjects were significantly more
      aggressive than the controls. 4. There was a significant correlation between the
      growth hormone response to buspirone and behavioral measures of aggression in the
      cocaine dependent subjects, but not in the controls. 5. There was no difference
      in the overall growth hormone response between the controls and cocaine dependent
      subjects, possibly due to differences in metabolism of buspirone. 6. This study
      supports a role for serotonin in aggression in cocaine dependent subjects.

PMID- 7824758
TI  - Loss of control of pre-motor activation in anxious agitated and impulsive
      depressives. A clinical and ERP study.
AB  - 1. Current research uses a variety of traditional validation methods in order to
      test the clinical expression of biological models in psychiatry. The application
      of these methods has resulted in a paradoxical situation which requires the
      definition of new objectives in biological and pharmacoclinical research: the
      biological specificity of new psychotropic drugs does not assume any congruence
      between their pharmacological and their therapeutic effects, but raises the
      question of the relationship between biological systems and clinical
      symptomatology. The dimensional description of psychopathological disorders may
      be more appropriate to biological studies in psychiatry. 2. A study was
      undertaken on a population of twenty-one in-patients fulfilling the DSM III-R
      criteria for major depressive episode. They were divided into two groups on the
      basis of contrasting clinical dimensions: anxious-agitation and impulsiveness
      versus retardation and affective blunting. 3. Significant clinical differences
      between the two groups on mood profiles were echoed by contrasts in event-related
      potentials during a go-nogo task: only anxious agitated and impulsive patients
      developed an abnormal cortical activity, as measured by contingent negative
      variation (CNV), in the nogo condition. 4. This paper suggests how a paradigm
      with control of motor action leads to specify premotor activation abnormalities
      in the agitated impulsive depression subtype.

PMID- 7824759
TI  - The central effects of moxonidine on intraocular pressure and its antagonism by L
      659, 066 and L-657, 743 in the rabbit.
AB  - 1) The imidazoline, moxonidine (MOX), injected icvt into the anterior lateral
      ventricle of NZW rabbits induced ocular hypotension (> 7.0 mmHg) that persisted
      for two hrs. 2) L-659, 066 injected i.v. or icvt inhibited MOX-induced ocular
      hypotension, significantly. 3) L-657, 743, injected icvt at 100-fold lower
      concentration than icvt L-659, 066, significantly inhibited MOX-induced ocular
      hypotension. 4) Alpha-2-adrenoceptors, located in the CNS, play a role in MOX
      induced ocular hypotension, as evidenced by the ability of the relatively
      selective alpha-2 antagonists, L-659, 066 and L-657, 743 to inhibit icvt MOX
      induced ocular hypotension.

PMID- 7824760
TI  - Effect of milnacipran and desipramine on noradrenergic alpha 2-autoreceptor
      sensitivity.
AB  - 1. The effects of chronic administration with milnacipran and desipramine on the
      noradrenergic alpha 2-autoreceptor sensitivity in the rat hypothalamus were
      compared. 2. Rats were administered, in their diet, milnacipran (50 mg/kg/day for
      21 days, 24 h wash-out), desipramine (35 mg/kg/day for 21 days, 24 h wash out) or
      desipramine (14 mg/kg/day for 21 days, 41 h wash-out). Hypothalamic slices were
      incubated with [3H]noradrenaline, superfused and stimulated electrically. 3.
      Chronic administration with milnacipran did not modify basal or electrically
      induced release of [3H]noradrenaline, tissue incorporation of [3H]noradrenaline
      or the sensitivity of the alpha 2-autoreceptor assessed by the inhibition of the
      stimulation-evoked release of [3H]noradrenaline by the alpha 2-adrenoceptor
      agonist, guanabenz, in comparison to controls. After chronic desipramine (35
      mg/kg), basal and evoked release of [3H]noradrenaline were increased, tissue
      incorporation of [3H]noradrenaline decreased and the inhibitory effect of
      guanabenz was diminished. At the lower dose (14 mg/kg), chronic desipramine
      increased only the evoked release of noradrenaline but did not modify the
      sensitivity of the alpha 2-autoreceptor. 4. Desipramine at 35 mg/kg remains in
      the tissue after 24 h wash out, causing a reduction of uptake and complicating
      the interpretation of the data.

PMID- 7824761
TI  - Participation of opioid and monoaminergic mechanisms on the antinociceptive
      effect induced by tricyclic antidepressants in two behavioural pain tests in
      mice.
AB  - 1. Various clinical and experimental reports indicate that tricyclic
      antidepressant drugs are specially useful in the treatment of chronic and acute
      pain conditions. The present work was aimed to study the mechanisms implicated in
      the antinociceptive response induced by these antidepressants on different
      experimental models of pain in mice, and particularly the role played by
      noradrenergic, serotonergic and opioidergic influences. 2. Electrical stimulation
      of the tail and formalin tests were used to evaluate pain perception in mice
      acutely treated with different antidepressants (imipramine, desipramine,
      amitriptyline, nortriptyline, clomipramine and desmethylclomipramine).
      Antinociceptive responses were more potent in formalin test than in tail
      electrical stimulation test. 3. These antinociceptive effects were inhibited by
      naloxone (2 mg/Kg, i.p.), alpha-methyl-p-tyrosine (200 mg/Kg) and p
      chlorophenylalanine (600 mg/Kg). Naloxone elicited the same effectivity to
      inhibit antinociceptive responses induced by tricyclic antidepressants in both
      tail electrical stimulation and formalin tests. alpha-methyl-p-tyrosine and p
      chlorophenylalanine were more effective on antinociceptive responses induced on
      formalin than in tail electrical stimulation test. 4. These results suggest that
      tricyclic antidepressants produce antinociception partly via the participation of
      the endogenous opioid system and partly by further activating noradrenergic and
      serotonergic pathways. Moreover, the analgesic responses and the mechanisms
      implicated were dependent of the analgesimeter test used.

PMID- 7824762
TI  - Enkephalinase inhibition and hippocampal excitatory effects of exogenous and
      endogenous opioids.
AB  - 1. The relationships between the in vivo and in vitro epileptogenic effects of
      opioids or enkephalins and the electrophysiological activity of inhibitors of
      endogenous enkephalinase were analyzed. 2. The functional effects of the
      inhibition of the endogenous enkephalinase has been compared with the role of the
      endogenous opioid peptidergic system in the control of neuronal excitability.

PMID- 7824763
TI  - A fixed-dose study of adinazolam-SR tablets in generalized anxiety disorder.
AB  - 1. This four-week, randomized, double-blind, multicenter study compared the
      efficacy and safety of adinazolam-SR, at three dosage levels, with placebo. Forty
      (40) patients were randomized at our site: 10 to adinazolam 30 mg/day, 10 to 60
      mg/day, 10 to 90 mg/day, and 10 to placebo. All patients were moderately anxious
      with Hamilton Anxiety Scale (HAM-A) scores of > or = 21 at baseline. 2. The data
      were analyzed by pooling the three adinazolam groups and comparing them with the
      placebo group using t-tests. HAM-A scores decreased significantly more in the
      pooled adinazolam-SR treatment group than in the placebo group at both Week one
      (p < .02) and at Week two (p < .01), as well as at endpoint (p < .03). 3. At
      endpoint the adinazolam-treated group included 8 "responders" (> or = 50%
      reduction on the baseline HAM-A score) while none of the placebo patients were
      responders (p < .05). Dose-response effects were evaluated and relationships were
      not statistically significant. 4. The results indicate that adinazolam-SR was
      clearly superior to placebo for the treatment of patients suffering from
      Generalized Anxiety Disorder.

PMID- 7824765
TI  - [The imaging diagnosis of osteoporosis. The state of the art and outlook].

PMID- 7824764
TI  - Proton spectroscopy of human brain: effects of age and sex.
AB  - 1. The present study was done to assess the brain metabolites measured by proton
      magnetic resonance spectroscopy (MRS) in normal individuals. 2. Proton
      spectroscopy STEAM voxel technique with chemical shift imaging was used to
      provide localized metabolic information from the brains of 34 normal volunteers
      (15 males) between the ages of 21 and 75 years. 3. Choline, Creatine and N-acetyl
      aspartate (NAA) was lower in white matter than gray matter. Choline/NAA and
      choline/creatine ratios were also lower in white matter. The choline, creatine
      and NAA were lower in older subjects in the voxel representing cortical and
      subcortical gray matter. There were no differences between males and females. 4.
      This preliminary study suggests that age matching is essential for comparative
      studies of disease states using proton MRS.

PMID- 7824766
TI  - [The role of computed tomography and magnetic resonance in assessing degenerative
      arthropathy of the lumbar articular facets].
AB  - Degenerative arthropathy of the lumbar facet joints remains a debated issue
      relative to both its etiopathogenesis and its clinical significance. The authors
      studied 9 autoptic specimens by means of CT and MRI: the diagnostic value of the
      two methods was assessed taking the histopathologic findings of the relative
      specimens as the gold standard. The following signs of degenerative arthropathy
      were investigated in each specimen: cartilaginous wears, hypertrophy of the
      articular processes, osteophytosis, subchondral sclerosis and geodes and capsular
      and ligamentous calcifications. CT clearly demonstrated the characteristic signs
      of arthropathy, although failing to assess the cartilaginous wears in the early
      degeneration phases. Cartilaginous surface tears were directly depicted by MRI in
      the specimens showing medium and advanced degeneration. In our opinion, CT
      represents the examination of choice in the diagnosis of degenerative arthropathy
      of the lumbar apophyseal joints. Nevertheless, human trials are needed to assess
      MR capabilities in better detailing subchondral bone structure and in depicting
      the joint capsule and the synovial membrane and fluid as a major MR potential to
      diagnose back pain syndromes arising from the posterior arch.

PMID- 7824767
TI  - [Loose bodies of the temporomandibular joint. A rare pathology].
AB  - Loose bodies of the temporomandibular joint (TMJ) are an uncommon condition which
      can be caused by various complaints that can now be diagnosed with high
      resolution CT. The authors report on 10 cases observed from 1983 to 1992 which
      were studied with both conventional radiography and CT. The most common
      conditions were synovial chondromatosis and osteochondrosis dissecans. In the two
      cases of synovial chondromatosis, the demonstration of ossified loose bodies made
      the diagnosis easier. The cases of osteochondrosis dissecans presented with more
      complex diagnostic problems: in two instances the characteristic subchondral bone
      fragment in the condylar head was clearly visible, but in the third case this
      small fragment was difficult to identify as it had migrated backwards, making the
      disorder troublesome to diagnose. An osteophyte fracture and the presence of a
      bone fragment following condylar head fracture were easily diagnosed by correctly
      assessing the associated articular changes resulting from an arthrosic and a
      traumatic condition, respectively. The only case of loose body due to previous
      TMJ remodeling was easily diagnosed as the totally ossified formation was not
      seen on the preoperative X-ray film. Finally, two very similar cases,
      characterized by the presence of an elongated radiopaque formation in the site of
      the posterior meniscal ligament, were difficult to interpret as no such case is
      reported in the literature. In both cases an anatomical variant was presumed,
      characterized by posterior meniscal ligament ossification.

PMID- 7824768
TI  - [The radiology of cerebral and paranasal sinus fungal lesions].
AB  - Pulmonary fungal infections have been increasingly reported in the patients with
      hematologic malignancies treated with aggressive chemotherapy and therefore
      presenting chemotherapy-induced leukopenia. The diagnosis of fungal infections in
      these severely immunocompromised hosts is of great importance, enabling the
      administration of an antifungal treatment to prevent potentially fatal fungal
      dissemination. This retrospective study was carried out to assess the most
      valuable conventional radiologic and CT features in the diagnosis of sinusal and
      cerebral mycosis infections. The authors reviewed their personal series of 71
      patients with malignant hematologic diseases who developed a fungal lesion:
      twenty-eight cases were selected, 10 of them with an autoptic diagnosis of
      cerebral fungal lesions and 18 with a bioptic diagnosis of paranasal fungal
      lesions. In 10 patients with encephalic lesions, CT enabled four main types of
      tomodensitometric alterations with fungine etiology to be singled out--i.e.,
      ischemic lesions, brain abscesses, granulomatoses and meningitis with possible
      brain parenchyma involvement. In 18 patients with fungal sinusitis, radiography
      and CT showed three main types of alterations: sinus opacities, pseudocystic
      images within the sinus and bone erosions. We conclude that in sinusal and
      cerebral fungal lesions no "specific criteria" can be established for the
      radiologic differential diagnosis between different fungine species and between
      fungine lesions with different etiologic agents.

PMID- 7824769
TI  - [Rotator cuff rupture in the shoulder impingement syndrome. Echography and
      arthrography: 2 diagnostic methods compared].
AB  - After briefly reviewing the shoulder impingement syndrome, the authors
      investigate the role of two diagnostic imaging methods, i.e., ultrasonography
      (US) and arthrography, in demonstrating the typical features of this condition.
      Over a 15 months' period, 190 patients suffering from shoulder pain were examined
      with arthrography; 50 of them subsequently underwent acromion plastic surgery and
      rotator cuff stitching. This study was aimed at comparing US and arthrographic
      results, applying classifiable criteria to make the most accurate diagnosis of
      rotator cuff tears. The lack of visibility of the rotator cuff at US was the
      major and clearest sign of tear (100% of cases). The association between cuff
      thinning and hypo/hyperechoic damaged focal areas was another major sign (in
      76.19% of complete tears and in 14.28% of incomplete tears). Hyperechoic focal
      areas alone proved to be a false-positive finding in 5 cases, while in 11 of 19
      cases normal US patterns were a false-negative finding; in 3 cases other
      conditions were diagnosed. To conclude, the value of US is emphasized in the
      screening of the painful shoulder and the use of arthrography is suggested when
      both clinical tests and US fail to yield enough information for a diagnosis to be
      made.

PMID- 7824770
TI  - [The computed tomographic semeiotics of rhino-sinusal inflammatory pathology].
AB  - Recent advances in "functional" endoscopic surgical techniques require the
      radiologist to understand the anatomy and pathophysiology of the nose and
      paranasal sinuses as well as their normal and abnormal CT patterns. Endoscopy and
      CT are complementary procedures, but in the evaluation of the extent of chronic
      inflammation and in the demonstration of possible associated local and regional
      complications, the latter method has become the imaging technique of choice,
      providing a detailed map for the functional sinus surgeon and replacing plain
      radiography. The authors reviewed a personal series of 322 coronal thin-slice CT
      examinations of the paranasal sinuses relative to 169 patients with chronic or
      acute sinusitis and polyposis. The main CT findings of sinusitis (mucosal
      thickening, fluid retention, mucous cysts, bone alterations, mucoceles and
      polyposis) and their complications are reported. Finally, ostiomeatal conditions
      are considered, particularly the obstruction of ducts and ostia which provide
      aeration and mucous clearance from the paranasal sinuses.

PMID- 7824771
TI  - [Diffuse ground-glass opacity of the lung. A guide to interpreting the high
      resolution computed tomographic (HRCT) picture].
AB  - The so-called ground glass pulmonary opacity is characterized by a slight
      increase in lung density, with persistent visibility of vascular structures and
      bronchial walls. If vessels are obscured, the term consolidation is preferred.
      This kind of pulmonary opacity, which may be patchy or diffuse, was well known in
      conventional radiology, but has been recently re-evaluated, following the
      increasingly widespread use of high resolution CT of the lung. Ground glass
      opacity is commonly observed in patients with early diffuse pulmonary
      infiltrative diseases. Though non-specific in itself, the sign is always very
      significant. Particularly, it could represent a useful sign of active and
      treatable abnormality in some diffuse pulmonary diseases, such as idiopathic
      pulmonary fibrosis and sarcoidosis. The ground glass opacity may also be observed
      in pulmonary edema, desquamative pneumonitis, Pneumocystis carinii pneumonia,
      alveolar proteinosis, hypersensitive pneumonitis and drug induced or radiation
      induced lung disease. This paper represents a contribution to the understanding
      of the pathologic bases of the ground glass pulmonary opacity and an introduction
      to its differential diagnosis.

PMID- 7824772
TI  - [The magnetic resonance imaging of abdominal aortic aneurysms].
AB  - The diagnostic role of Magnetic Resonance Imaging (MRI) was investigated in the
      study of abdominal aortic aneurysms and compared with that of Computed Tomography
      (CT) and digital subtraction angiography (DSA). Magnetic Resonance angiography
      (MRA) was performed on 21 patients with radiologically proved abdominal aortic
      aneurysms, using a superconductive 1.5 T magnet (GE, Signa Advantage); the 2D TOF
      technique with gradient-echo sequences was used (SPGR: FA 45-60 degrees, TR/TE
      33/7, ST 2 mm, 1 nex, 256 x 128 matrix, inferior presaturation and flow
      compensation). The images acquired on the axial plane were reconstructed
      according to MIP and rotated on the z-axis from +90 degrees to -90 degrees. In
      all cases SE 2D T1- and T2-weighted sequences were acquired on the axial plane.
      Twelve patients were examined with MRI, CT and DSA; 3 with MRI and CT; 2 with MRI
      and DSA and finally 4 with MRI only. The radiologic studies were then reviewed
      blind and the results of the different methods compared. In all cases MRI yielded
      similar information to CT and DSA as to aneurysm extent and size, vessel
      involvement, status of visceral, iliac and common femoral arteries and finally
      the conditions of perianeurysmatic tissues. The authors conclude that MRI is a
      useful and accurate technique for the preoperative examination of abdominal
      aortic aneurysm patients.

PMID- 7824773
TI  - [Color Doppler echography of the orbit. Its normal aspects and pathological
      conditions with vascular involvement].
AB  - This study was aimed at investigating the role of color-Doppler US in the
      assessment of orbital vasculature under normal conditions; the results were then
      applied to the flowmetric analysis of some vascular diseases of the orbit, i.e.,
      retinitis pigmentosa, simple chronic glaucoma, low-tension glaucoma and carotid
      cavernous fistulas. The study consisted of two phases: first, a group of 20
      healthy volunteers was examined and then 39 patients were divided into 4
      subgroups. The patients (18 men and 21 women, age range: 52-68 years) were
      further divided into 4 subgroups: 12 of them had retinitis pigmentosa, 15 simple
      chronic glaucoma, 8 low-tension glaucoma and 4 carotid-cavernous fistulas. Color
      Doppler yielded useful pieces of information on the position of orbital vessels
      and flow direction, while pulsed Doppler allowed the measurement of several
      variables, i.e., time average velocity, protosystolic velocity, peak systolic
      velocity, mesodiastolic velocity, end diastolic velocity, resistive index and
      pulsatility index. The study of the 20 healthy volunteers yielded valuable
      information on the anatomy and flow patterns of some vessels, such as the
      ophthalmic artery, the central retinal artery, the lacrimal artery and the
      posterior ciliary arteries, all of them visible in 90-100% of patients; the
      central retinal vein, the superior ophthalmic vein and venae varicosae were
      demonstrated in about 10-30% of them. In the group of patients, the mean flow
      velocities of the examined arteries were significantly lower than those in the
      normal volunteers; in the patients with carotid-cavernous fistulas an ectasic
      superior ophthalmic vein was demonstrated, with its typical flow
      "arterialization" pattern. The results suggest that color-Doppler could play a
      mayor role in the study of ocular hemodynamics.

PMID- 7824774
TI  - [Color Doppler and phlebography in the Paget-Schroetter syndrome].
AB  - The authors compared the adequacy of phlebography and color-Doppler US in the
      diagnosis of subclavian-axillary thrombosis, or Paget-Schroetter syndrome. Ten
      patients with subclavian-axillary thrombosis (8 men and 2 women, aged 16 to 55
      years, mean age: 30 years) were examined over a two-year period. All of them
      underwent color-Doppler US and conventional phlebography in the same session. US
      findings were in agreement with phlebographic results in all cases as to
      thrombosis presence and site. The thrombosis involved the subclavian-axillary
      vein in 8 cases, the subclavian-innominate vein in 1 case and both veins in 1
      case. Color-Doppler US, however, yielded no information relative to the superior
      vena cava; these data were always obtained with phlebography even though in 4
      cases that segment had to be studied with phlebographic opacification via
      contralateral route. Furthermore, US failed to clearly demonstrate the thrombosis
      involving the last axillary valve; preserving this valve is indeed the main aim
      of fibrinolysis since its integrity, at this level, prevents venous reflux
      independent of subclavian-axillary trunk recanalization, thus reducing the severe
      symptomatologic sequelae following postphlebitic damage. Phlebography showed the
      valve and its possible involvement in all cases. In 4 cases phlebography also
      demonstrated compressive thoracic inlet syndrome, which had been missed by US,
      yielding the main anatomic elements for following surgery. To conclude, the
      authors suggest noninvasive color-Doppler US as the screening method of choice,
      while phlebography remains the gold-standard technique to be performed in all
      Doppler positive cases: in fact, the latter method yields more pieces of
      information and is more panoramic than the former, besides allowing fibrinolysis
      effects to be studied and the possible presence of an associated thoracic inlet
      syndrome to be investigated.

PMID- 7824775
TI  - [The reliability of echotomographic diagnosis in assessing thyroid lesions. A
      comparison with cytology and histology].
AB  - The authors report their personal experience in 160 patients affected with
      thyroid conditions examined with US and fine needle aspiration (FNA). Benign
      nodular hyperplasia, cystic-colloid nodular hyperplasia, colloid cyst,
      hemorrhagic cyst, adenoma, thyroiditis, follicular and malignant lesions were
      studied. The latter consisted of 5 papillary carcinomas, 6 follicular carcinomas,
      1 medullary carcinoma, 1 Hurthle cell carcinoma, 1 lymphoma and 1 metastatic
      lesion. The following US patterns were observed: 69.2% of the malignant lesions
      were hypoechoic, 15.4% were hyperechoic and 7.7% isoechoic. Most of the malignant
      lesions (84.6%) had inhomogeneous echo texture; 46.1% of them exhibited
      peripheral microcalcifications. US diagnoses were compared with cytologic and/or
      histologic findings to assess US accuracy. In the surgical patients US accuracy
      reached 78.6% in benign lesions and 61.5% in malignant lesions. Since US alone
      fails to yield enough pieces of information for an accurate diagnosis to be made,
      especially when malignant lesions are concerned, FNA should be used, while trying
      to define the actual role of color-Doppler US.

PMID- 7824776
TI  - [Echography and integrated imaging in the diagnosis of hyperparathyroidism].
AB  - The authors report their personal experience with US, CT, biopsy and, lately,
      MRI, to localize enlarged parathyroid glands in primary and secondary
      hyperparathyroidism. December 1986 through December 1993, sixty-four primary and
      55 secondary hyperparathyroidism patients were examined--119 in all. At biopsy
      and surgery, US sensitivity appeared to be 72%, with 0.94 positive predictive
      value; CT sensitivity was 80% with 0.91 positive predictive value. The two
      methods combined had 87% sensitivity in all. In the authors' experience, US
      proved to be a sensitive, accurate and cost-effective technique, as well as the
      best method to guide biopsy thanks to its multiplanar capabilities. Even though
      it requires great operator's experience, US is the method of choice in the
      localization of abnormal parathyroid glands. Its combination with CT increased
      overall sensitivity mainly in ectopic localizations and postoperative
      recurrences. Finally, technologic progress and increased MR sensitivity are
      likely to make MRI the imaging technique of choice, replacing CT, in the
      diagnostic protocol of hyperparathyroidism.

PMID- 7824777
TI  - [The coronal anatomy of the pelvis at rest and under straining].
AB  - Twenty-five subjects with no pelvic floor dysfunctions at defecography were
      examined with direct coronal CT scans of the pelvis at rest and on straining.
      Three compartments with different characteristics were delimited by two planes
      the anterior one being tangent to the ischiatic foramen and the posterior one to
      the ischial tuberosities. At rest, the average length of the levator ani muscle
      and the surface of the supralevator space were significantly lower posteriorly
      than in the other two compartments (48.3 mm +/- 7.9; 48.8 mm +/- 7; 42.6 mm +/-
      9.4, p < 0.05 and 70.6 cm2 +/- 7.5; 66.9 cm2 +/- 11.2; 27.2 cm2 +/- 4.8, p <
      0.01, respectively). On straining, maximum muscle lengthening occurred
      posteriorly, as indicated by similar average values (63.7 mm +/- 12.7; 63.3 mm +/
      9.5 and 60.5 mm +/- 14) and the corresponding increase (+12.5%) in the
      supralevator space occurred in the middle compartment (73.8 cm2 +/- 7.6; 75.3 cm2
      +/- 11.6 and 30.2 cm2 +/- 5.2). To conclude, our method proved reliable enough
      (intra- and interobserver correlation index > 80%) and promising for future
      clinical applications and studies of pelvic floor dysfunctions.

PMID- 7824779
TI  - [CT-guided celiac ganglion block. The authors' own experience].
AB  - Celiac plexus neurolysis is considered an effective technique for relieving
      abdominal cancer pain. CT yields accurate anatomical detailing, thus allowing the
      indirect location of the celiac plexus and the planning of needle trajectory and
      positioning. September 1992 to December 1993, twenty-eight celiac plexus
      neurolyses for pain relief were performed in 26 patients (13 men and 13 women),
      17 through the anterior and 11 through the posterior access. These patients had
      been referred to our department for pain management. Forty-eight hours after
      alcoholization, 20 patients (71%) had complete pain regression and their
      analgesic treatment was thus discontinued. 36% of the patients did not need any
      analgesics for 30 to 169 days. No neurologic complications were observed. Only
      transient orthostatic hypotension requiring no treatment developed in all our
      patients during the first 24 hours after the block. To conclude, we believe
      celiac plexus alcoholization under CT guidance to be a safe and effective
      technique for relieving abdominal pain due to cancer or benign conditions. We
      prefer the anterior approach because it is better accepted by the patients and
      more easily performed by the operators.

PMID- 7824778
TI  - [The preoperative chemoembolization of hepatocarcinoma due to cirrhosis].
AB  - PURPOSE: To investigate clinical value and tumor response of preoperative
      transcatheter arterial chemoembolization for hepatocellular carcinoma (HCC)
      secondary to cirrhosis. MATERIALS AND METHODS: The clinical, radiologic and
      histologic findings were reviewed relative to 13 cirrhotic patients operated on
      for HCC after chemoembolization with an emulsion of Lipiodol UF and epirubucin;
      additional gel-foam embolization was performed in 12 cases. RESULTS: The mean
      survival was 24 months. Three patients died within 1 month after surgery; 2 other
      patients died 10 and 32 months after surgery, respectively. The 2-year recurrence
      rate was 40%. Tumor size, the grade of iodized oil retention and the embolization
      technique affected primary tumor necrosis ratio: most of satellite nodules and
      capsular invasions were persistently viable at histology. CONCLUSIONS:
      Preoperative chemoembolization neither facilitates, nor contraindicates, HCC
      surgery. Nevertheless, chemoembolization should always be performed before
      surgery first to stage the patients with Lipiodol CT and second to administer the
      first palliation whenever the patient is ineligible for surgery.

PMID- 7824781
TI  - [Is informed consent necessary in radiotherapy?].

PMID- 7824780
TI  - [The compression of numerical radiological images].
AB  - A digital radiological image is made by a number of pixels, each of them
      characterized by a definite numerical value obtained by quantization which
      represents the luminance in that specific image unit. Spatial resolution and
      dynamic range are the main factors in determining the quality of a digital
      radiological image. The product of the two above factors defines the global
      dimensions of the image and is expressed in bits. In conventional radiographic
      images the global dimension of the image is expressed in MBytes, because of its
      high spatial and contrast resolution. To reduce the visualization and storage
      requirements as well as the transmission time of large image data sets,
      compression algorithms have been recently introduced. These algorithms are based
      on the fact that often in a digital image parts of the binary data are
      "redundant", that is they are not necessary for correct image representation.
      Therefore, compression methods are aimed at reducing both statistical and
      perceptive redundancy. Statistical redundancy is reduced by means of lossless
      coding which does not allow to compress images with a ratio higher than 4-5:1 and
      that--by definition--allows to recover the original image quality. On the other
      hand "lossy" compression algorithms, which eliminate the perceptive redundancy,
      are based on the reduction of spatial resolution and dynamic range and on
      transform-based methods. In particular, the latter have usually been more
      successful in terms of efficient compression, even when applied to conventional
      radiographic images. The basic transform procedure can be modified at various
      levels. JPEG is one of these methods, originally developed for photographic
      images, which can be usefully applied to radiological images as well. Lossy
      procedures allow to reach higher compression ratios than lossless methods, but
      the decrease in information content must be prevented from reducing diagnostic
      accuracy. In order to assess the diagnostic efficiency of the images compressed
      with lossy methods, semi-objective analyses are usually performed and ROC curves
      are produced and evaluated. A model ROC analysis is presented.

PMID- 7824782
TI  - [An expert system for the planning of whole-body irradiation treatments].
AB  - Total body irradiation (TBI) combined with intensive chemotherapy and bone marrow
      transplantation is used with increasing success for the treatment of hematologic
      malignancies with severe prognosis. An expert system, developed on the basis of
      the experience acquired during the last years in our department, has been
      designed to optimize the different treatment steps. The choice of an expert
      system is based on its capabilities in reconstructing a rule-based reasoning
      through the combination of theoretical and empirical knowledge. Particularly, a
      subsystem dealing with the steps to be taken to optimize treatment in TBI has
      been designed using medical and physical data. Our system can determine radiation
      treatment variables together with a sequence of quality control procedures.
      Moreover, indications are given about short, medium and long term damage
      probabilities and toxicity estimates, both derived from literature data and our
      personal series of cases. Treatment quality can be assessed and the different
      techniques compared using these data. This project is aimed at providing
      physicians and physicists with useful clinical suggestions for TBI setting for
      bone marrow transplantation.

PMID- 7824783
TI  - [Accelerated radiotherapy with the concomitant-boost technic in patients with
      squamous cell carcinoma of the head and neck].
AB  - The purpose of this phase I-II study was to assess the efficacy and toxicity of
      an accelerated radiation therapy schedule in patients affected with head and neck
      squamous cell carcinomas of various primary sites. We adopted the concomitant
      boost technique which allows 1-2 weeks' shorter treatment time by delivering the
      boost treatment phase as second daily dose during the last part of the basic
      field irradiation. May 1989 to December 1992, fifty-one patients were scheduled
      to receive a total dose of 71-75 Gy in 40 fractions over 6 weeks. The boost
      encompassing the macroscopic disease was given as second daily dose during the
      last two weeks of the basic treatment. Severe mucositis was observed in 62% of
      the patients. Late side-effects occurred in 4 patients. At a median follow-up of
      two years (range: 12-56 months), actuarial locoregional control rate is 44% and
      overall survival is 54%. At univariate analysis, primary site is the only
      predictive factor of locoregional control (p = 0.009): neoplasms arising from the
      oral cavity did worse than those from larynx/hypopharynx and oro/nasopharynx. We
      conclude that this regimen is feasible in head and neck squamous cell carcinoma
      of various primary sites. However, since primary site seems to exhibit a
      predictive value, data from controlled studies are needed to assess its role in
      primary sites other than oropharynx and nasopharynx.

PMID- 7824784
TI  - [Interstitial brachytherapy in carcinoma of the lip. Case histories and results].
AB  - Squamous cell carcinomas of the lip can be treated by surgery or radiation
      therapy. Since local control rates exceed 90% with both treatment modalities,
      therapy is chosen according to functional and cosmetic results, to the patient's
      wishes and to the physician's medical policy. This study was aimed at
      retrospectively reviewing our local control results and patterns of failure
      relative to survival as well as evaluating the results according to technical
      surgical variables. From 1982 to 1991, sixty-nine patients with squamous cell
      carcinoma of the lip received a course of interstitial brachytherapy with 192Ir.
      The disease stage was T1 in 36 cases, T2 in 12 cases and T3 in 2 cases and 19
      recurrences; 3 patients only had clinically detectable lymph nodes at diagnosis.
      Interstitial brachytherapy was used as postoperative treatment, at a dose of 60
      Gy, in 47 cases. As an exclusive curative approach brachytherapy was given at a
      reference dose of 65 Gy, with a medium dose rate of 62.88 cGy; a single plane was
      used in 55 cases, a triangular plane in 11 and a double plane in 3 cases. In one
      patient only the disease persisted and no local failures were observed. Overall
      actuarial survival at 5 years is 76.81% (91.3% when corrected for disease). In
      fact, 6 patients died of disease progression: 3 with lung metastases, 1 with bone
      metastases and 3 with lymph node metastases. Five patients died of cancer in
      other sites--i.e., ovary, lung, prostate, hypopharynx, stomach--and 4 of non
      neoplastic diseases. Tolerance rates were excellent, with only one mucosal
      necrosis which resolved spontaneously; no sequelae were observed in gums, teeth
      and jaws. The cosmetic result was also excellent in most of the cases with a
      worsening trend for multiplanar disposition. In conclusion, interstitial
      brachytherapy can be considered the treatment of choice for early lip cancer.

PMID- 7824785
TI  - [Carcinoma in situ of the breast: which treatment?].
AB  - From January 1984 to December 1992, twenty-eight patients affected with breast
      carcinoma in situ were treated with surgery (8 with radical mastectomy, 20 with
      quadrantectomy) at Umberto I Hospital in Mestre, Italy. The patients with
      multicentric lesions and treated with quadrantectomy received also radiation
      therapy. The dose was 50 Gy/25 fractions with 60Co and a boost of 10 Gy to the
      tumor bed. The mean age of our patients was 55 years (range: 34-74 years).
      Histology diagnosed lobular carcinoma in situ in 7 cases, intraductal carcinoma
      in 19 cases and comedocarcinoma in 2 cases. The median and the mean follow-up are
      37 and 42 months (range: 24-128), respectively. The eight-year local control and
      the cause-specific survival rates are 100%. No local relapses have been observed.
      One patient died, of another neoplastic disease, free from breast disease. We
      believe that the conservative approach in breast carcinoma in situ, according to
      literature results and to our personal experience, should be more frequently
      preferred to radical surgery even in the patients with multicentric lesions.

PMID- 7824786
TI  - [The current role of radiotherapy in immunogenic exophthalmos].
AB  - In this study, the value of radiation therapy was investigated in 41 patients
      with Graves' ophthalmopathy treated with orbital irradiation at the Radiotherapy
      Department of Mauriziano Hospital in Turin, 1986 through 1993. Our series
      consisted of 41 patients (32 women and 9 men), whose mean age was 53.6 years
      (range: 26-72 years). All patients had a high index of endocrine ophthalmopathy,
      based on the American Thyroid Association classification-NOSPECS classes III and
      IV. Irradiation was administered with two opposed convergent beams tilted
      posteriorly 5-10 degrees with 20 Gy/12 fractions/2 weeks. The total dose
      delivered to the lens was than 5%. The follow-up consisted of endocrinologic and
      ophthalmologic tests and, if possible, of pre/post-irradiation orbital US. A
      positive result was obtained in 31 patients, which was very good in 22 of them.
      Severe complications, i.e., 1 corneal ulceration and 3 cataracts, were observed
      in the patients with associated ocular conditions and were treated simultaneously
      with high-dose corticosteroids so that no direct and unquestionable correlation
      can be made between irradiation and complications. To conclude, our data show
      that radiation therapy can improve the signs and symptoms of Graves' disease, as
      many authors report.

PMID- 7824788
TI  - [The radiological diagnosis of a case of osteoid osteoma of the base of the
      skull].

PMID- 7824787
TI  - [Adjuvant radiotherapy in rectal neoplasms. Survival analysis,local control,
      prognostic factors and toxicity].
AB  - January 1985 to June 1991, seventy-five patients affected with surgically treated
      rectal cancer received adjuvant postoperative irradiation at the Radiation
      Therapy Department of the Ospedale S. Maria Nuova, Reggio Emilia, Italy. Forty
      seven patients had Astler-Coller B2-B3 lesions and 28 had stage C2-C3 disease.
      The patients underwent postoperative irradiation (range: 44-60 Gy, median: 48.5
      Gy) with a 60 Co unit, most of them with conventional fractionation; no patient
      received adjuvant chemotherapy. A local boost was used in 19 cases (5.4-14 Gy);
      actuarial 5-year overall and disease-free survival rates were 55.2 +/- 10.5% and
      53.4 +/- 10%, respectively; actuarial 5-year local control was 78.7 +/- 10.5%. In
      11 cases (14.5%) chronic sequelae were observed; 6 cases required surgical
      intervention. In 42% of cases the disease relapsed, locally in 12 patients (16%).
      In conclusion, our results are in agreement with literature data; adequate and
      innovative techniques are required to decrease treatment-related toxicity.

PMID- 7824789
TI  - [Hydatidosis located in the clavicle. The echographic observation of a case].

PMID- 7824790
TI  - [The magnetic resonance aspects in a case of chondrosarcoma of the hand].

PMID- 7824791
TI  - [The cardiac migration of a caval filter].

PMID- 7824792
TI  - [The role of imaging in a rare case of the total dislocation of an aortic valve
      prosthesis that migrated into the abdominal aorta].

PMID- 7824793
TI  - [Thoracic duct dilatation in a case of lymphangioleiomyomatosis. The computed
      tomographic and magnetic resonance aspects].

PMID- 7824794
TI  - [The ileocolic changes in a case of adult-onset cystic fibrosis].

PMID- 7824795
TI  - [The echo-radiographic diagnosis of a case of the colonic invagination of an
      appendiceal mucocele].

PMID- 7824796
TI  - [A giant diverticulum of the sigmoid. A report of 2 cases].

PMID- 7824797
TI  - [The imaging of extraneural cysticercosis by echography, computed tomography and
      magnetic resonance. A report of a case with cutaneous and costal localizations].

PMID- 7824798
TI  - [The association of microlithiasis and malignant testicular neoplasms. The
      echographic pictures in one patient].

PMID- 7824799
TI  - [The positioning of 2 caval filters in a case of duplication of the vena cava
      inferior].

PMID- 7824800
TI  - [Stenosis of a carotid bypass. Its treatment by percutaneous angioplasty].

PMID- 7824801
TI  - [Congenital malformation of the sternum].

PMID- 7824802
TI  - [The 1994 SIRM Prize. L'Associazione Italiana di Radiologia Medica. The winning
      research project. Advanced methods for assessing mineral density and bone
      architecture].

PMID- 7824803
TI  - Quantification of T cells reactive to Pf155/RESA peptides in Plasmodium
      falciparum-exposed individuals.
AB  - This study was designed to estimate, among T lymphocytes circulating in the
      peripheral blood of donors exposed to malaria parasites, the frequencies of those
      responding to Plasmodium falciparum antigens, and more specifically to Pf155/RESA
      peptides. The values of peptide-reactive T-cell frequencies were dispersed and
      rather low, ranging from 1:24,000 to undetectable (superior to 1:300,000).
      Subjects presented with different past exposure to parasites: either they had
      been repetitively exposed to malaria parasite infestation or they were recovering
      from a recent treated malaria attack. However, they had similar frequencies of T
      cells reactive to Pf155/RESA peptides. With cells from a minority of patients,
      "saw-tooth curves" were obtained, suggesting the existence of suppressor
      mechanisms operating in vitro in our limiting dilution assay.

PMID- 7824804
TI  - Functional beta-glucan receptor expression by a microglial cell line.
AB  - In the central nervous system, the functions of microglia appear crucial after
      brain damage, when phagocytes eliminate cell debris, acting as the scavengers of
      the brain. Diseases where an active role for microglia has been proposed recently
      include Alzheimer's disease, the acquired immune deficiency syndrome (AIDS) and
      multiple sclerosis. Only recently has it been possible to obtain a microglial
      cell line retaining morphological and functional aspects of these cells and their
      secretory products. Sugar receptors are expressed by a variety of phagocytes in
      primary cultures, but in contrast, are absent on the majority of the described
      macrophage-like cell lines. We here establish, by 4 degrees C binding
      experiments, that this murine cell line, called BV-2, expresses a high level
      (9.86 +/- 0.91 x 10(5); n = 3) of beta-glucan receptors. At 37 degrees C, BV-2
      cells show high phagocytic power that can only be inhibited by the free polysugar
      beta-laminarin (a poly-glucose) and not by mannan (a poly-mannose) as described
      for macrophages. The beta-glucan receptor expressed by the microglial cell line
      BV-2 is fully functional in phagocytosis of unopsonized heat-killed yeast
      particles.

PMID- 7824805
TI  - Effect of ammonia on endocytosis, cytokine production and lysosomal enzyme
      activity of a microglial cell line.
AB  - Ammonia is a natural lysosomotropic compound. Concentrations of ammonium acetate
      > 2 mM impaired the phagocytic activity of BV-2 cells, an immortalized microglial
      cell line, as was determined by the uptake of fluorescent latex microspheres of
      different sizes. In contrast, an increase in the uptake of fluorescent dextran
      was observed with the elevation in ammonium acetate concentrations. This
      indicates that ammonia affects phagocytotic and pinocytotic activities of BV-2
      cells differently. Interferon-gamma- and polyinosinic-polycytidylic acid
      stimulated secretion of IL1 alpha as well as LPS-stimulated secretion of IL6
      decreased with an elevation in ammonium acetate concentrations. The constitutive
      secretion of IL1 alpha was not significantly affected by ammonium acetate.
      However, an increase in LPS-stimulated IL1 alpha secretion was observed at 10 mM
      and 20 mM ammonium acetate. High concentrations of ammonia affected the activity
      of lysosomal enzymes of the BV-2 cells. Acid phosphatase and alpha-glucosidase
      activities increased with the increase in ammonium acetate up to 20 mM. The
      activity of cathepsin D was increased at 5 mM, but decreased at higher ammonia
      concentrations. The effects of ammonia on microglial functions are discussed with
      respect to pathogenetic mechanisms of dementia of the Alzheimer type.

PMID- 7824806
TI  - Which steps in lymphocyte recirculation are regulated by interferon-gamma?
AB  - Lymphocyte traffic throughout the body is a basic mechanism of immune
      surveillance. Most studies of the regulation of the extravasation of lymphocytes
      have focused on the interaction between endothelial cells of the high endothelial
      venules (HEV) in lymphoid organs and lymphocytes via the interaction of various
      adhesion molecules. Cytokines play a major role in the regulation of immune
      reactions, and some have been shown to upregulate adhesion molecules important
      for lymphocyte migration. Using interferon-gamma (IFN gamma) as an example of
      such a cytokine, we summarize the available data on regulation by IFN gamma of
      the different phases of lymphocyte migration from the blood via HEV, through the
      lymphoid organ and finally exiting the organ. Much data obtained in in vitro
      assays have not yet been confirmed in vivo, and therefore a number of questions
      remain unanswered. Our hypothesis is that the interaction of lymphocytes with
      endothelial cells represents just one aspect of regulation, and that lymphocyte
      migration is probably regulated much more effectively within the lymphoid organ.

PMID- 7824807
TI  - Molecular Bases of Immunity, 1994. Proceedings of the 1994 ENII (European Network
      of Immunology Institutes) Conference. Les Embiez, France, May 18-22, 1994.

PMID- 7824808
TI  - The role of anticholinergics in 'stable' chronic obstructive pulmonary disease:
      unanswered questions.

PMID- 7824809
TI  - Efficacy and tolerance of a 12-week treatment with inhaled formoterol in patients
      with reversible obstructive lung disease.
AB  - Formoterol, a new beta 2-agonist, and salbutamol were given as aerosols twice and
      four times daily, respectively, to patients with reversible obstructive lung
      disease. The study was controlled and double blind, and continued for 12 weeks.
      Ninety-nine patients from five study centers were included and 89 patients could
      be properly evaluated. The formoterol-treated patients used significantly less
      rescue medicine (salbutamol aerosol) and had higher morning PEF values. For the
      other efficacy variables (daytime FEV1.0, evening PEF, patient and investigator
      global evaluations, night sleeping time) and tolerance (side effects noted by
      patients, blood and urine laboratory values, ECG, patient and investigator global
      evaluation), there were no significant differences between the formoterol- and
      the salbutamol-treated groups.

PMID- 7824810
TI  - Severe exacerbations of chronic obstructive pulmonary disease treated with BiPAP
      by nasal mask.
AB  - Bi-level pressure support ventilation via a nasal mask (NIPSV) was provided to 28
      consecutive unselected patients with acute respiratory failure due to
      exacerbation of chronic obstructive pulmonary failure (COPD). If NIPSV improved
      gas exchange within 2 h, it was continued. Otherwise, patients would be promptly
      intubated. The patients median age was 68 years (minimum 56, maximum 82). The
      arterial blood gas drawn before initiating NIPSV showed (FiO2 21%) a mean PaO2 of
      41.3 +/- 6 mm Hg, a mean PaCO2 of 66 +/- 15 mm Hg and a mean pH of 7.31. Upon
      admission the mean respiratory rate was 36 breaths/min and the median Apache II
      score was 20.5 (minimum 13, maximum 32). Despite oxygen administration all
      patients failed to improve their PaO2 and/or showed a consistent and dangerous
      hypercapnic response. NIPSV was performed with a median inspiratory positive
      airway pressure of 14 cm H2O (minimum 10, maximum 20) and a median expiratory
      positive airway pressure of 4 cm H2O (minimum 3, maximum 6). Eighteen patients
      (64%) were successfully ventilated with NIPSV, while in 10 (36%) NIPSV failed. A
      high Apache II score, but not admission blood gas exchange or respiratory rate,
      seems to be correlated with the failure to ventilate with NIPSV. The results of
      our preliminary experience suggest the use of NIPSV as an initial approach to
      acute respiratory failure due to exacerbation of COPD, particularly in patients
      with an Apache II score of less than 29.

PMID- 7824811
TI  - The pulmonary vascular response to acute hypoxia in chronic pulmonary disease:
      morphological assessment with magnified pulmonary wedge angiography.
AB  - To detect hypoxic pulmonary vasoconstriction (HPV) morphologically, we
      investigated the pulmonary vascular response to acute hypoxia in 27 patients with
      chronic pulmonary disease (CPD) and 8 healthy subjects. Pulmonary hemodynamic
      measurements and magnified pulmonary wedge angiography (MPWA) were carried out
      before and after inhalation of 13% oxygen in nitrogen for 15 min. The diameters
      of central arteries (A) and muscular arteries (B) were measured using a
      densitometric method. Vasoconstriction was detected in the muscular arteries than
      in the central arteries by MPWA. There was a significant correlation between
      delta P (changes of mean PA pressure) and delta B/A (changes in diameters of B/A)
      in the CPD group. A significant correlation was found between delta SvO2 and
      delta B/A in the control group. We conclude that MPWA was a very useful method
      for the simple detection of HPV in patients with CPDs and we detected one site of
      HPV on the ninth generation of the pulmonary arterial tree by MPWA.

PMID- 7824812
TI  - Scintigraphy, angiography and computed tomography in unilateral hyperlucent lung
      due to obliterative bronchiolitis.
AB  - This study examines the value of different imaging methods in assessing the
      anatomic structures of unilateral hyperlucent lung due to obliterative
      bronchiolitis. We studied 9 patients, 5 males and 4 females, suffering from UHL
      (mean age 49 years). Ventilation-perfusion scan (VPS) and computed tomography
      (CT) of the chest were performed in all, and conventional angiography or digital
      substraction angiography (DSA) in 7 patients. The VPS showed the characteristic
      pattern of a matched ventilation-perfusion defect and considerable air trapping
      during the washout phase. Conventional angiography and DSA displayed a smaller
      pulmonary artery on the affected side, with a poor peripheral vasculature. CT
      displayed a loss of lung volume in all cases, with diminished mean attenuation
      values, a markedly diminished vasculature and integrity of the main airways. In
      contrast to other imaging modalities, CT imaged bronchiectasis, which was the
      cause of the patients' clinical symptoms of bronchorrhea and hemoptysis. We
      conclude that CT of the chest is the most valuable imaging method for evaluating
      unilateral hyperlucent lung, particularly in symptomatic patients.

PMID- 7824813
TI  - Chromosome analysis in pleural effusions. Efficiency of this method in the
      differential diagnosis of pleural effusions.
AB  - Various laboratory methods are being used to acquire diagnosis in pleural
      effusions. However, about 20% of the effusions cannot be diagnosed reliably.
      Cytogenetic analysis in pleural effusion is not used routinely, although many
      numerical and/or structural chromosome abnormalities have been observed in
      malignant pleural effusions. In this study, a total of the 61 pleural effusion
      samples, 34 malignant which included 19 diffuse pleural malignant mesothelioma,
      15 metastatic malignant pleural effusions and 27 benign, were analyzed by direct
      chromosome analysis method. To the findings obtained in the study, 85.3% (29/34)
      of the 34 patients with malignant pleural effusion had numerical and/or
      structural abnormalities, and 3 of them had no mitosis. The patients who had
      benign pleural effusion indicated no numerical and/or structural abnormalities.
      We have concluded that if a pleural effusion cannot be reliably differentiated by
      the usual laboratory methods and especially malignancy is strongly suspected,
      cytogenetic analysis can be used to differentiate malignant effusions from benign
      effusions with a small rate of error, and also it can indicate that more invasive
      diagnostic procedures are necessary.

PMID- 7824814
TI  - The anti-inflammatory drug nimesulide inhibits neutrophil adherence to and
      migration across monolayers of cytokine-activated endothelial cells.
AB  - Neutrophil migration through the microvascular endothelium represents a
      fundamental event for the cell accumulation at sites of tissue injury. Owing to
      their capacity to modify the structural and functional characteristics of
      endothelial cells, inflammatory cytokines such as interleukin-1 (IL-1) and tumor
      necrosis factor-alpha (TNF alpha) play a pivotal role in directing circulating
      neutrophils away from the bloodstream to the interstitial tissue. In order to
      study neutrophil transendothelial migration, human umbilical vein endothelial
      cells were grown to confluence on the polycarbonate filter of two-compartment
      migration chambers. Pretreatment of the endothelial cell monolayers with TNF
      alpha for 4 h resulted in rapid migration of approximately 50% of subsequently
      added neutrophils across the layers. In contrast, < 10% of added neutrophils
      penetrated untreated endothelial monolayers. Using TNF alpha-treated endothelium,
      neutrophil transmigration was inhibited by the methane sulfonanilide anti
      inflammatory drug nimesulide. Moreover, neutrophil adherence to TNF alpha-treated
      endothelial monolayers, cultured in microtiter wells, was markedly reduced by
      nimesulide. A linear correlation between the drug-dependent inhibition of
      neutrophil transmigration and neutrophil adherence was found. Finally, nimesulide
      did not interfere with the TNF alpha ability to convert resting endothelium into
      a pro-adhesive and pro-locomotory cell layer. The data suggest that nimesulide
      reduces neutrophil transendothelial migration primarily by limiting the cell
      anchorage to the TNF alpha-activated endothelium. Therefore, the drug has the
      potential to down-regulate neutrophil extravasation and, in turn, the burden of
      neutrophil oxidants and proteases leading to tissue injury at sites of
      inflammation.

PMID- 7824815
TI  - Pulse oximetry during fibreoptic bronchoscopy in local anaesthesia: frequency of
      hypoxaemia and effect of oxygen supplementation.
AB  - The indication for oxygen supplementation during diagnostic fibreoptic
      bronchoscopy (FOB) in local anaesthesia was evaluated by means of pulse oximetry
      in 160 patients (108 men, 52 women), median age 62 years. The patients were
      allocated at random into four groups of each 40 persons, which were comparable
      concerning pulmonary function and the dose of benzodiazepine used for
      premedication. The oxygen saturation of the haemoglobin (SpO2) in the tip of the
      index finger and the pulse rate were continuously recorded. Group 1 was examined
      without O2 supplement. Group 2a received O2 2 litres/min through a catheter
      placed in the vestibulum nasi. Group 2b received O2 2 litres/min through a
      pharyngeal catheter. Group 3 received O2 3 litres/min through a pharyngeal
      catheter. SpO2 mean values during FOB were 92 +/- (SD) 3% in group 1 and 96 +/-
      2% in groups 2a, 2b and 3 (p < 0.001). SpO2 trough levels were mean 87 +/- 4% in
      group 1 vs. 93 +/- 2% in groups 2a and 2b, and 94 +/- 3% in group 3 (p < 0.001).
      Transient hypoxaemia, i.e., SpO2 < 85%, occurred with a frequency of 35% in group
      1, 2.5% in group 2a, 0% in group 2b, and 2.5% in group 3. Tachycardia and
      bradycardia during FOB occurred with a frequency of 20% in group 1, 25% in group
      2a, 18% in group 2b, and 10% in group 3. Pulse oximetry increases the safety of
      FOB, and is recommended for routine use. During FOB, oxygen supplement 2-3
      litres/min should be administered to all patients, preferably through a
      pharyngeal catheter, as a preventive measure against hypoxaemia.

PMID- 7824816
TI  - Successful surfactant replacement therapy in two infants with ARDS due to
      chlamydial pneumonia.
AB  - We report two cases of adult respiratory distress syndrome (ARDS) treated
      successfully with repeated doses of a bovine natural surfactant (Survanta). Two
      former premature infants developed severe respiratory failure as a consequence of
      a chlamydial pneumonia at the age of 3 or 12 weeks, respectively. As both
      patients were threatened by hypoxia in spite of mechanical ventilation with
      maximal pressures using 100% O2 and as the X-rays were compatible with the
      diagnosis of ARDS, we decided to perform rescue surfactant treatment. Following
      surfactant instillation, marked improvement in oxygenation and ventilatory
      requirements was observed. Within 2 h after surfactant replacement, the PaO2/FiO2
      ratio increased from 52 to 84 (case 1) and from 35 to 94 (case 2), and the peak
      inspiratory pressure could be reduced from 47 to 40 cm H2O and from 35 to 28 cm
      H2O, respectively. Both infants received a second surfactant dose about 10 h
      after the initial treatment and survived without developing chronic lung disease.

PMID- 7824817
TI  - Intracellular multiplication of Legionella pneumophila in Tetrahymena
      thermophila.
AB  - It has been shown that Legionella pneumophila proliferates intracellularly in
      more than ten species of protozoa, but the fate of the bacteria in Tetrahymena
      thermophila has not been reported. We investigated the multiplication of L.
      pneumophila Philadelphia-1 strain in micronucleated T. thermophila, and the
      effects of temperature and numbers of the bacteria ingested by the protozoa after
      in vitro feeding were studied. T. thermophila preyed actively upon the bacteria.
      After being ingested, the fate of the bacteria was affected by both temperature
      and the number of bacteria ingested. When the number of ingested bacteria was 30
      per protozoon, the bacteria proliferated intracellularly at 35 degrees C. The
      bacteria, however, could not proliferate at 28 degrees C or 32 degrees C though
      they survived in the protozoa. When the ingested bacteria was 10 per protozoon,
      the bacteria were killed in the protozoa at all of the temperatures tested.
      Electron microscopic examination revealed that the protozoa ingesting the
      bacteria remarkably swelled and that protozoan food vacuoles which contained L.
      pneumophila were studded with ribosomes.

PMID- 7824818
TI  - Expression of (Na, K) ATPase/Ca-ATPase chimeric proteins in Xenopus oocytes
      revealed that the COOH-terminal one-third of the (Na, K) ATPase alpha-subunit is
      involved in assembly with the beta-subunit.
AB  - Chimeric proteins consisting of parts from the alpha-subunit of Torpedo
      californica (Na, K) ATPase (N) and the rabbit sarcoplasmic reticulum Ca-ATPase
      (C) were expressed in Xenopus oocytes by injecting the respective chimeric cRNA
      in combination with cRNA for the beta-subunit of Torpedo (Na, K) ATPase. The
      chimeric protein (NCN) that consisted of the NH2-terminal and COOH-terminal one
      thirds of the alpha-subunit of the (Na, K) ATPase and the central one-third of
      the Ca-ATPase was able to assemble with the beta-subunit in the same fashion as
      the wild-type alpha-subunit of the (Na, K) ATPase (NNN). On the other hand,
      chimeric proteins in which the COOH-terminal one-third was derived from the Ca
      ATPase (NNC and NCC) were unable to form stable complexes with the beta-subunit.
      These results suggest that the COOH-terminal one-third of the (Na, K) ATPase
      alpha-subunit is required for the assembly with the beta-subunit.

PMID- 7824819
TI  - Health-related worries, perceived health status, and health care utilization.
AB  - This study examines the association of health-related worries (over cancers,
      diabetes, work-related stress, heart attack, obesity, general physical fitness,
      and/or other health conditions) and perceived health status (excellent, good,
      fair or poor) to the utilization of health care services for 19, 139 Japanese
      local public service employees. Data on health-related worries and health status
      were obtained from a self-administered questionnaire survey in 1988 and analyzed
      in relation to the subsequent 12-month utilization of health care. Results showed
      that perceived health status was associated with the utilization for almost all
      medical conditions and so was worry over a specific condition and the subsequent
      utilization of health care services. The implication of these findings is that
      measures targeting the relief of an employee's health-related worries, through
      either health consultation or other health programs, may contribute to the
      reduction of an employee's health care utilization and costs.

PMID- 7824820
TI  - [Details of a magnetic resonance system (SIS 200/400) for experimental small
      animals].
AB  - Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS)
      employing the nuclear magnetic resonance (NMR) phenomenon were used as a non
      invasive method for obtaining anatomical images and for studying intracellular
      metabolism in vivo. A SISCO SIS 200/400 MRI/MRS experimental system for small
      animals (4.7 tesla, 400 mm bore) was set up, and its installation was completed
      in October 1993. The system makes it possible to obtain excellent quality animal
      images and to analyze a cellular metabolism in vivo. We introduce the details of
      our particular system, computers, data processing and image resolution together
      with examples of rat and puppy images.

PMID- 7824821
TI  - Peak expiratory flow rate of jute mill workers in Calcutta.
AB  - Ventilatory capacity of 32 control and 318 asymptomatic male jute mill workers of
      the Calcutta area, India was measured by Wright's Peak Flowmeter. Mean values of
      peak expiratory flow rate (PEFR) was 514 +/- 66.41 l/min in Control and 475 +/-
      66.02 l/min and 462 +/- 67.42 l/min in exposed non-smoker and smoker workers
      respectively. The relationship of PEFR with age, height, duration of exposure and
      smoking habit were studied. Multiple regression techniques were used to determine
      the form of the relationship of age, height, exposure and smoking habit with
      PEFR. The findings have been compared with those of Indian and foreign authors.
      The possible reasons of difference includes smoking habit, occupational exposure,
      physical background and residence in polluted area etc.

PMID- 7824822
TI  - "Sensing" patient needs: exploring concepts of nursing insight and receptivity
      used in nursing assessment.
AB  - Nursing assessment utilizes skills that enable the nurse to "sense" the patient's
      needs and the patient's condition, and that provide a humanistic dimension to the
      provision of nursing care. The explanatory concepts describing these processes
      include intuition, emotional empathy, inference, knowing, counter transference,
      compathy and embodiment. In this paper these concepts are defined, and the more
      commonly used concepts (i.e., intuition, empathy, and inference) are compared.
      The underlying assumptions and characteristics are identified and the antecedents
      or prerequisites, mechanisms, and outcomes of each concept are explored. While
      some overlap and blurring of boundaries are evident, these concepts are diverse
      and were developed to apply to different contexts and non-nursing situations.
      When used alone, none is comprehensive enough to account for nurses' ability to
      sense patient needs. We conclude that, given the unique aspects of nursing, we
      must consider using innovative methods to examine this phenomenon (e.g., the use
      of ethology to examine intuitively perceived changes in the patient's condition),
      to increase efforts to explore the newer concepts (i.e., embodiment, compathy and
      "knowing"), and to develop new concepts or models that better represent this
      complex phenomenon that better fits nursing contexts and situations.

PMID- 7824823
TI  - The influence of experience on community health nurses' use of the similarity
      heuristic in diagnostic reasoning.
AB  - This study explored the diagnostic reasoning of community health nurses,
      examining the association between nursing experience and use of the cognitive
      heuristic similarity. Two types of similarity reasoning were examined, similarity
      to a single prototype (SSP) and similarity to a population prototype (SPP). The
      hypothesis of the study, derived from heuristics theory and ACT theory predicted
      that experts would be more likely to make diagnoses by similarity assessment than
      less experienced nurses. A random sample of 214 community health nurses was
      studied. Each subject completed eight diagnostic problems included in the
      Clinical Inference Questionnaire (CIQ) that was developed for this study to
      measure judging by similarity. Most of the nurses in this study, regardless of
      experience, used similarity assessment as a basis for some diagnoses. Experts
      were more likely than less experienced nurses to judge by similarity in
      population prototype problems but not in single prototype problems. These
      findings suggest that the diagnostic process includes similarity reasoning and
      imply that this process cannot be well understood without further exploration of
      the role of cognitive heuristics.

PMID- 7824824
TI  - Perspectives on activity.
AB  - Activity is integral to human health, well-being, development, and functioning.
      Despite its importance to health, there have been few efforts to develop
      conceptual definitions of activity as a basis for nursing research in this area.
      The purposes of this paper are to review the major attributes of physical
      activity found in the nursing and health care literature, to formulate a
      comprehensive definition of activity based on the literature, and to suggest
      directions for future research.

PMID- 7824825
TI  - Caregiver planning for a demented parent by adult offspring with and without
      crisis experience.

PMID- 7824826
TI  - [Childhood vaccinations: current status 1994].
AB  - During the last decades, progresses in the field of vaccination entailed a better
      control of many infectious diseases, even to their complete or nearly complete
      eradication. However, progresses in this field can still be realised. This paper
      brings the attention of the practioners on the new trends contributing to
      improve, in our country, the rate of immunization owing to a better attention for
      applying the present vaccination schedule and introducing new vaccines.

PMID- 7824827
TI  - [Virology: diagnosis or screening?].
AB  - Andre Dachy is a sensitive clinician as well as a microbiologist who knows about
      hidden meanings of laboratory tests. Pediatrics was enriched by his dual interest
      in observation of the children and of the microbes which threaten them. As time
      went by, Dachy's interest for social medicine grew. Thus, it is justified to
      address him the present consideration on relevancy of virology diagnosis and
      modalities of screening.

PMID- 7824828
TI  - [Iodine nutrition and neonatal hypothyroidism].
AB  - This paper summarizes the research activities and the actions conducted and
      implemented by the author during the past 30 years in the field of the disorders
      induced by iodine deficiency and by neonatal hypothyroidism. This work was
      conducted within the framework of the activities of the author in the Department
      of Pediatrics in Saint-Pierre Hospital. The work resulted in original
      contributions to epidemiology, etiopathogenesis, clinical manifestations,
      diagnostic procedures, complications, prevention and therapy of the disorders
      resulting from iodine deficiency or neonatal hypothyroidism. Special attention
      was devoted to the prevention of impairment of brain and intellectual development
      resulting from both conditions in the infant.

PMID- 7824829
TI  - [Obstetrical and perinatal outcome of patients not covered by medical insurance].
AB  - The number of pregnant women uncovered by medical insurance is increasing in the
      maternity of Saint-Pierre Hospital (44% increase over a 3 year period). During
      the academic year 92-93, this situation was present in 9.8% of the mothers; 98%
      of these patients were foreigners. The majority of pregnancies were not or poorly
      followed. Admissions occurred very often in emergency situations. The lack of
      prenatal care in this population with a very low socio-economic level led to a
      six-fold increase in perinatal mortality after exclusion of congenital
      malformations (58.4% versus 8.7%). This high mortality rate was mainly due to
      extreme prematurity (birthweight between 500 and 1500 g).

PMID- 7824830
TI  - [Ambulatory pediatrics in the hospital and at home].
AB  - In paediatrics, ambulatory care under hospital control is ensured both by the out
      patient department and by the emergency unit. If socio-economic level and
      parental availability are taken into account, the hospital remains the most
      accessible health-care structure in large towns. The common illnesses, in most
      cases infectious and respiratory, should not encumber the emergency unit, but
      should instead be taken in charge by a structure where an extended-timetable
      dispensary and an out-patient clinic by appointment work in parallel. In the most
      favourable cases, a home care unit completes this out-patient structure. Its main
      characteristics are as follows: it is exclusively paediatric, and it aims at
      shortening or avoiding hospitalization. It improves the quality of treatment,
      provides the family with medico-social support and follow-up that is particularly
      useful in less favoured settings, and can also offer preliminary training in
      heavy or chronic cases. Notwithstanding its obvious advantages, budgetary cuts
      have led to the suppression of home care at Hopital Saint-Pierre in 1983.

PMID- 7824831
TI  - [Contribution of digestive system ultrasonography in the assessment of abdominal
      pain in children].
AB  - The quality of modern ultrasonography allows to study not only solid abdominal
      organs but also digestive walls and abdominal lymphnodes, leading to accurate
      diagnosis in many cases, and decreasing the use of more aggressive radiological
      procedures (upper GI baryum studies, baryum enema, intravenous pyelography,
      etc.). In dealing with abdominal pain in children, the plain XRay film of the
      abdomen and abdominal echography are performed immediately after history taking
      and physical examination, and are equally important in the work up of these
      cases.

PMID- 7824832
TI  - [The abused child: activities of the SOS-children team of the Saint Pierre
      Hospital].
AB  - Child abuse has emerged in the past twenty-five years as a visible and important
      social, physical and mental health concern. We have tried to present some general
      approaches of the phenomenon: our goals are to protect the interest of the child
      and to develop help for the abusing parents, through crisis interventions and
      long-term coordination with the medico-social network.

PMID- 7824833
TI  - [The child exposed to the human immunodeficiency virus].
AB  - The care of the child exposed to human immunodeficiency virus extends beyond the
      treatment of the medical complications of the illness. It begins during the
      pregnancy by an individualised decision regarding the indication of a
      prophylactic intervention to reduce the risk of mother-to-child transmission of
      the virus, includes after delivery the attempt of early diagnosis of the vertical
      transmission and offers, during each of these circumstances, counselling and
      social support. A multidisciplinary team, associating pediatricians, nurses,
      social workers and psychologists, a close collaboration with obstetricians and
      internists, as well as the access to an expert laboratory are the keys to answer
      the challenges of this disease.

PMID- 7824834
TI  - Coxsackievirus infection and the development of polymyositis/dermatomyositis.
AB  - Recently, it has been suggested that coxsackievirus plays an etiologic role in
      juvenile dermatomyositis (DM). Neutralizing antibodies to 12 coxsackievirus
      antigens were measured in the sera of four clinical subsets of patients with
      adult polymyositis (PM)/DM. Elevated antibody titers to coxsackievirus A7, B3,
      and B4 were detected in patients with adult PM, adult DM, and adult PM/DM with
      malignancy, respectively. The development of these three subsets of idiopathic
      inflammatory myopathies may be related to infection with specific coxsackievirus
      serotypes.

PMID- 7824835
TI  - Soluble interleukin-2 receptor in sera and synovial fluids of rheumatoid
      patients: correlations with disease activity.
AB  - The measurement of serum soluble interleukin-2 receptor (sIL-2R), a sensitive
      marker of lymphocyte activation, has been proposed as an indicator of disease
      activity and "outcome" in patients with inflammatory diseases characterized by
      the activation of immune cells. Serum sIL-2R levels have been reported higher in
      rheumatoid patients than in controls. Using an enzyme-linked immunoabsorbent
      assay (ELISA), we evaluated soluble IL-2R levels in the serum of 34 patients with
      RA and in the synovial fluid of 25 of these patients and we compared it with
      levels found in the serum of 13 healthy controls. Serum sIL-2R levels were
      significantly elevated in RA patients compared with the healthy age-matched
      control group (P < 0.005). The mean level of soluble IL-2R in synovial fluids was
      significantly higher than the mean sera levels in RA patients (P < 0.0001).
      Moreover, we examined the correlation between serum and synovial fluid sIL-2R
      levels and disease activity measures. Serum sIL-2R correlated only with ESR (P <
      0.04). The synovial fluid sIL-2R correlated with ESR (P < 0.02) and a visual
      analogue scale (VAS) pain score (P < 0.04). Both serum and synovial fluid sIL-2R
      levels correlated with the chronic arthritis systemic index (CASI; P < 0.04 and P
      < 0.005, respectively). Our data suggested that in RA the measurement of sIL-2R
      may certainly mirror the degree of chronic inflammation and the continuous
      activation of the immune cells in the joint, although the role of this molecule
      in the immune response is still unclear.

PMID- 7824836
TI  - Psychiatric symptoms before systemic lupus erythematosus is diagnosed.
AB  - Psychiatric symptoms are rarely reported as an initial feature of systemic lupus
      erythematosus (SLE). Nevertheless, many patients have the feeling that
      psychiatric symptoms occurred before they were diagnosed as having SLE. This
      feeling was confirmed by an enquiry among members of the Dutch Lupus Patients
      Society: half of them had experienced psychiatric complaints before SLE was
      diagnosed. Two-thirds of these patients searched for professional help for these
      complaints. This motivated us to study whether SLE patients were admitted into
      psychiatric hospitals without being diagnosed as having SLE. Sera from 2121
      patients admitted to a psychiatric hospital and from 500 controls matched for sex
      and age were tested for the presence of antinuclear antibodies (ANA) and
      antibodies to DNA. ANA were found in 3% of patients, as well as controls. Anti
      DNA antibodies were found in 1% of both patients and controls. Two out of 114
      patients psychiatric patients with ANA and/or anti-DNA antibodies had SLE and/or
      Sjogren's syndrome. We concluded that SLE is not an important cause of admission
      to psychiatric hospitals. Routine tests for the determination of antinuclear and
      anti-DNA antibodies on admissions in these hospitals thus would not seem useful.
      To study whether patients with another chronic disease also had psychiatric
      complaints before being diagnosed, we performed the same enquiry among members of
      the Dutch Sarcoidosis Patients Society. The results were almost equal to those of
      the enquiry of the members of the Dutch Lupus Patients Society. Why members of
      both societies so often report psychiatric symptoms before their disease is
      diagnosed should be a subject of further studies.

PMID- 7824838
TI  - How could infectious agents hide in synovial cells? Possible mechanisms of
      persistent viral infection in a model for the etiopathogenesis of chronic
      arthritis.
AB  - It has been hypothesized that a persistent intra-articular viral infection might
      play an important part in the pathogenesis of chronic arthritis. However, it
      remains unclear how such an infection could survive in synovial cells that
      express large amounts of HLA-DR and intercellular adhesion molecule-1 (ICAM-1) by
      which they communicate with immunocompetent cells. In an in vitro model of
      persistent mumps virus infection of synovial cells, results suggested that, in
      contrast to mock-infected cells, cells containing viral antigen did not express
      HLA-DR in response to interferon-gamma and that they did not up-regulate ICAM-1
      expression under these conditions. Previously it has been shown that infected
      synovial cells do not express viral surface antigens. By these mechanisms,
      infected cells, interspersed among a large majority of uninfected cells, might
      evade recognition and eradication by the immune system. Lack of neoantigen
      expression on infected cells might be an important viral strategy to maintain a
      persistent infection and to initiate and perpetuate joint inflammation.

PMID- 7824837
TI  - HLA class II genes and antibodies against recombinant U1-nRNP proteins in
      patients with systemic lupus erythematosus. SLE Study Group.
AB  - To investigate a possible involvement of HLA-class II alleles in the genetic
      predisposition for the formation of anti-U1-nRNP antibody-in systemic lupus
      erythematosus (SLE), genomic DNA of 178 patients was typed for the DRB1, DQA1 and
      DQB1 alleles using a polymerase chain reaction (PCR) and non-radioactive
      oligonucleotide typing. Antibodies against recombinant U1-nRNP proteins (U1-A-,
      U1-C- and 70K-protein) were determined by ELISA. Anti-U1-C antibody was found in
      26 (14.7%), anti-U1-A in 34 (19.2%) and anti-70K in 17 (9.6%) patients. A joint
      occurrence was observed for these antibodies against the recombinant U1-nRNP
      proteins: anti-U1-C and anti-U1-A antibodies occurred together more frequently
      than alone and than together with anti-U1-70K antibodies. The frequency of
      DRB1*04 was slightly increased in the patients with anti-U1-C as compared to the
      patients without anti-U1-C (P < 0.05, Pcorr = n.s., RR = 2.4). The DQA1*0301
      allele, which is in linkage disequilibrium with DRB1*04, is found more frequently
      in anti-U1-C-positive than in antibody-negative patients. The DQB1*0303 allele,
      detected in 12 of 176 SLE patients, was absent in the patients with any of the
      antibodies against the U1-nRNP proteins. All these deviations may be due to
      chance alone. We concluded that the presence of antibodies against recombinant U1
      nRNP proteins was not significantly associated with any HLA DRB1, DQA1 and DQB1
      allele in our group of SLE patients.

PMID- 7824839
TI  - Anti-inflammatory effects of recombinant human manganese superoxide dismutase on
      adjuvant arthritis in rats.
AB  - The anti-inflammatory effects of recombinant human manganese superoxide dismutase
      on adjuvant arthritis was investigated. Local application of this manganese
      superoxide dismutase given every 2 days not only significantly reduced foot
      swelling but also retarded radiological bone destruction in adjuvant arthritis.
      Copper zinc superoxide dismutase had little effect on foot swelling.

PMID- 7824840
TI  - Interrelationship between synovial fluid interleukin (IL)-6, IL-1 beta and
      disease activity indices in rheumatoid arthritis.

PMID- 7824841
TI  - [Epidemiology of tobacco use in health-science students].
AB  - The characteristics of tobacco use by students of the Division of Health Sciences
      of the University of Barcelona have been studied. During the 1988-1989 school
      year, 382 students were individually interviewed about their use of tobacco by
      means of a questionnaire routinely used by the Department of Health and Social
      Security of the Generalitat of Catolonia (Spain), with pertinent modifications
      for this specific group. These interviews were performed by appropriately trained
      personnel. Information was also gathered on the influence of university-level
      studies on smoking habits, the effect of advertising and the efficacy of
      antitobacco programs and campaigns carried out by the government. The study
      sample was drawn from lists supplied by the registrars' offices, by means of a
      random sampling by school (Medicine, Pharmacy, Psychology, Odontology and
      Nursing). The prevalence of tobacco use was 40.8% (29.8% daily smokers and 11%
      occasional smokers). These results are similar to those described in the
      literature, although these values are somewhat higher than those in more
      developed countries with a longer tradition of resistance to the use of tobacco.
      It is important to note that studying health sciences does not appear to be a
      major influence on the student's habits, but that the social and cultural
      environment is the factor which weighs the most in this respect. In conclusion,
      to reduce the prevalence of tobacco use in this important group, educational
      programs must be begun at the pre-university level (secondary school) and changes
      should be made in the curricula of the health professional so that areas related
      to tobacco use are more motivational for students.

PMID- 7824842
TI  - [Mosquitos of peri and extradomiciliary environments in the southern region of
      Brazil].
AB  - Mosquitoes were collected on Sonho Real farm, Querencia do Norte county, Parana
      State, Brazil, using human bait and Falcao traps between June 1989 and May 1990.
      The fauna composition, monthly density, hours of major density, human attraction
      and presence of mosquitoes in domestic animal shelters were investigated. 5,923
      mosquitoes of the genera Aedes, Aedomyia, Anopheles, Coquillettidea, Culex,
      Mansonia, Psorophora, Sabethes and Uranotaenia were collected. 33 species of
      mosquitoes were identified and among them Aedes scapularis, Anopheles albitarsis,
      Aedomyia squamipennis, Coquillettidea lynchi, Mansonia titillans e Coquillettidea
      venezuelensis were predominant. All these species were captured mainly on human
      bait, except Aedomyia squamipennis that was captured in domestic animal shelters.
      With regard to all the mosquitoes captured (5,923), their major period of
      activity was between 18 and 19 hours and April was the month of greatest density.

PMID- 7824843
TI  - [Use of capture erytroimmunoadsorption test in the immunodiagnosis of
      neurocysticercosis].
AB  - The capture erytoimmunoadsorption (C-EIA) test was standardized for detection of
      Taenia solium cysticercus-IgG specific antibodies in cerebrospinal fluid (CSF)
      from patients with neurocysticercosis. For the C-EIA test performance a reagent
      for specific antibody detection was prepared using sheep's red blood cells (SRBC)
      in a concentration of 0.25% sensitized with crude saline extract antigen (SEA)
      obtained from Cysticercus cellulosae. The optimum concentration of SEA for SRBC
      sensitization was 40 micrograms/ml. The yield of SEA was 0.1 microgram
      protein/cavity. When 58 CSF samples from patients with neurocysticercosis were
      analysed the sensitivity of the test was found to be 84.5% and the confidence
      limit of 95% probability (CL95%) ranged from 75% to 94%. The specificity was
      95.3% (CL 95% from 90.7% to 99.9%) when CSF samples from the control group were
      analysed. The C-EIA test was shown to be efficient for neurocysticercosis
      diagnosis and important for public health laboratories, because of its low cost,
      high reagent yield and case of use.

PMID- 7824844
TI  - [Serum levels of vitamin A, E, C and B2, carotenoid and zinc in hospitalized
      elderly patients].
AB  - Serum levels of carotenoids, zinc and vitamins A, E, C and B2 were measured in al
      (n = 202) the elderly patients hospitalized in different wards of the hospital
      studied from February 1986 to October 1988. The study was conducted on 130 men
      and 72 women with a mean age of 67.8 years (range: 60 to 88 years). The
      percentage of nutritional deficiency was 59.5% for zinc, 56.5% for vitamin C,
      34.5% for vitamin B2, 25.9% for vitamin E, 13.2% for vitamin A, and 6.8% for
      carotenoids. Elderly patients with leucoses, megaesophagus, chronic obstructive
      pulmonary disease, and congestive heart failure represent a group with a high
      prevalence of deficiency both of zinc and of the vitamins under study. These
      results show the importance of detecting deficiencies of these micronutrients and
      provide a basis for a more rational approach to the treatment of elderly
      patients.

PMID- 7824845
TI  - [Mercury content in bleaches sold in the southeastern region of Brazil].
AB  - In order to determine the mercury content present as a contaminant in samples of
      bleach used in water and food disinfection, a method for sample treatment using
      chloridric acid to eliminate the chlorine was proposed. The technique of cold
      vapour atomic absorption spectrophotometry, used to quantify the mercury, showed
      a recovery of 103%. Sixty nine samples of bleach were analysed and the values
      found for the median and 90th percentil were respectively, 15 and 67
      micrograms/L. According to the values of residual mercury found and using the
      quantities of bleach recommended by the Brazilian Sanitary Authorities, the use
      of these disinfectants offers no risk to human health.

PMID- 7824846
TI  - [Quality evaluation of primary health care in an urban area of southern Brazil].
AB  - A 10% sample of patients who attended two Primary Health Care Units (PHCU) in
      Pelotas, RS (Brazil) was studied cross-sectionally for the purpose of measuring
      qualitatively the attention being offered to the population. According to
      domicilliar interviews, 15 days after their appointments, a solution (cure or
      improvement) was achieved in 87.9% of the patients. Patients or parents
      satisfaction (in the case of pediatric patients) was observed in nearly 90% of
      the sample. Patient satisfaction and solution were statistically associated (p =
      0.04). Association between the solution and the availability of medicines in the
      PHCU was observed. Patients who had received the whole or a part of their
      treatment had 33% greater probability of solving their problem. Professional
      satisfaction was linearly associated with both perception of a better
      professional-patient relationship (PR = 3.48; CI95%2.17-5.59) and the expectation
      of a better patient prognosis (PR = 1.99; CI95%1.36-2.91).

PMID- 7824847
TI  - [The discourse of the "fight against drugs" and its ideologies].
AB  - The ideological contents of the literature on drug consumption and addiction with
      a moralistic and enforcement approach are analysed from a scientific and public
      health point of view. A non-literal sense is brought out so that the discourse
      may be understood in its original context and its links with the forms of power
      present in social relations. The theory of discourse analysis is used as the
      appropriate methodology by which the ideological indicators that impose on the
      texts on drugs a predetermined bias are to be found. The results clearly reveal a
      persuasive discourse that has the propose of directing and manipulating ways of
      being and seeing in society, allowing the authors to be seen as interested
      parties in a heavy-handed system for the maintenance "of the social status quo".
      The conclusion is that in these tests, it is not really the drug question in
      itself that is dealt with, but rather a mythical construction, used do combat
      social deviation.

PMID- 7824848
TI  - [Calculation of recommendations regarding protein intake: their application to
      preschool, school students and adults taking Brazilian foods].
AB  - The recommendations for protein consumption depend on the essential amino acid
      and total nitrogen content of a diet, and food digestibility. International
      recommendations are based on egg or milk proteins. However, populations eat
      different food mixtures. Brazilians use rice and beans as their main protein food
      source. This study presents different Brazilian diets, with variable amount of
      rice and beans. The results show that for each diet there is a different amount
      of protein recommended. Pre-school children, for example, must receive from 1.15
      to 1.77 g/protein/day, depending on the mixture of their dietary protein intake.
      Besides the diet protein's quality and quantity, the total food intake and
      presence of other essential nutrients, such as iron, calcium and vitamin C has
      also to be considered. The correct protein recommendation with respect to a diet
      or a mixture of food, should take into consideration: digestibility, total
      nitrogen, essential amino acids, presence of others nutrients and weight of food
      consumed.

PMID- 7824849
TI  - [Economic evaluation and decision making in environmental health].
AB  - Due to the increasing deterioration of the environment and its possible
      consequences for the health of the population the design and implementation of
      policies for the control of economic activities according to criteria for the
      protection of human health and the environment itself have become an
      unquestionable need. Such policies would include the economic feasibility of
      existing alternatives for protection. Due to the huge interests involved,
      however, other factors, both social and political should also be taken into
      consideration. Economic evaluation has been seen as a promising foundation for
      the decision making process in this subject. This tool's capacity systematically
      to organize and compare the costs and the benefits of the alternatives for the
      solution of environmental problems is analysed. The main characteristics of cost
      benefit and cost-effectiveness studies are summarized, as well as the possible
      forms of economic evaluation, of the environment and the details of this field
      for the application of such techniques of analysis. The limits of these tools for
      the quantification of the non-monetary costs of environmental risks and the
      consequent damage to health, whether as pain, suffering or the disability of non
      economic ally active persons are set out as these constitute the methodological
      challenge of the economic evaluation in the area. The importance of the
      enhancement of information input for the decision-making process relating to
      environmental health issues such as the distributions of costs and benefits among
      the different social groups is scrutinized. Lastly, the growing political concern
      with environment issues is stated, as well as the technical possibility of the
      manipulation of these analytical tools. On the basis of these elements, the need
      for evaluators to be conscious on the political implications of their studies, as
      well as the importance of their relationship with the decision-makers in view of
      the need for effective relevance to current environmental issues.

PMID- 7824850
TI  - [Toxicology of toluene: aspects related to its abuse].
AB  - Toluene, present in many industrial and domestic products, is the main solvent
      involved in solvent abuse and occupational exposure. The main problem in studying
      toluene-related pathologies is the fact that it is frequently combined with other
      substances. This review focuses on its potential toxicity. The following subjects
      are discussed: pharmacologic parameters; physico-chemical features; exposure;
      clinical trials; experimental research; diagnosis; tolerance and dependence;
      acute and chronic effects; neurotoxicity; teratogenicity; psychiatric disorders;
      carcinogenicity; and treatment. It is concluded that is important more research
      on larger population samples with a view to better definition of the consequences
      of chronic use should be undertaken.

PMID- 7824851
TI  - [Onchocercosis expansion in Brazil].

PMID- 7824852
TI  - [Epidemiological expression of other sexually transmitted diseases among AIDS
      patients].
AB  - This study was carried out in order to estimate the frequency of other sexually
      transmitted diseases (STD) among AIDS patients and to identify their
      epidemiological association and possible relations to the groups most exposed to
      the virus. The data were collected from the medical case histories and the STD
      were identified on the basis of data provided by anamnesis, physical examination
      and laboratory examinations. Of the total of HIV/AIDS patients assisted at the
      hospital studied (S. Paulo State, Brazil), between January 1986 and January 1992,
      207 were included as sample subjects for this survey. Of the patients studied, 88
      (42.5%) had some other STD and 119 (57.5%) had no other STD, equivalent to a
      proportion of 0.7 STD patients-STD to each non-STD patient. The most prevalent
      STD identified were hepatitis B (33.3%), syphilis (30.3%) and gonorrhoea (12.9%).
      Concerning the means of transmission by which the patients had probably been
      infected with HIV, blood transmission was the most prevalent (44.9%); followed by
      sexual contact (21.3%); sexual/blood (17.9%); in 25.9% it was undetermined. In a
      particular comparison of sexual and blood transmission and the presence of other
      STD a statistical difference in those cases that were exposed to sexual
      transmission was observed.

PMID- 7824853
TI  - Associated disorders in coeliac disease: clinical aspects.

PMID- 7824854
TI  - Electric stimulation of the esophageal mucosa. Perception and brain-evoked
      potentials.
AB  - BACKGROUND: Brain potentials have been used to assess somatosensory, visual, and
      auditory function, whereas few attempts have been made to evoke brain potentials
      from viscera. METHODS: The present study evaluated perception and brain
      potentials evoked by electric stimulation at four different intensities in the
      esophagus of healthy volunteers. Results were compared with somatosensory evoked
      potential variables. RESULTS: In 6 of 10 subjects the two highest esophageal
      stimulus intensities caused a deep pain perception. A positive correlation
      between average esophageal stimulus intensity and age was demonstrated. The
      amplitude of brain potentials increased significantly as a function of both
      esophageal and cutaneous stimulus intensity. The latency of esophageally evoked
      potentials decreased with stimulus intensity and was substantially longer than
      cutaneously evoked potentials despite a comparable conduction distance.
      CONCLUSIONS: The present methods provide possibilities to assess sensory
      mechanisms and perception related to the human esophagus.

PMID- 7824855
TI  - Dissociated effect of nicotine on pentagastrin-stimulated acid secretion and
      blood flow in the rat stomach.
AB  - BACKGROUND: Knowledge of the effect of parenteral nicotine on physiologic gastric
      hyperemia is limited. This study examined the effect of intravenous nicotine on
      gastric hyperemia and and secretion induced by pentagastrin. METHODS: In starved,
      urethane-anesthetized rats, gastric corpus blood flow was monitored continuously
      in a localized area of the mucosa, using laser Doppler flowmetry. The tip of the
      laser Doppler flow probe was positioned against the mid-gastric corpus mucosa
      along the greater curvature. Intravenous nicotine (4 or 40 micrograms/kg/min) or
      vehicle was infused. RESULTS: The gastric acid secretion stimulated by
      intravenous pentagastrin, 20 micrograms/kg/min, was completely inhibited by both
      doses of nicotine. In contrast to previous reports based on the clearance of weak
      bases for gastric mucosal blood flow measurement, neither dose of nicotine
      altered the hyperemia induced by pentagastrin. CONCLUSION: A dissociated effect
      of intravenous nicotine on pentagastrin-stimulated gastric acid secretion and
      hyperemia is documented.

PMID- 7824856
TI  - Ultrasonographic assessment of fasting liquid content in the human stomach.
AB  - BACKGROUND: Disturbed antroduodenal motility plays an important role in the
      pathophysiology of functional dyspepsia (FD). Such motility disturbances can be
      investigated by transcutaneous ultrasound. When it is measured in a standardized
      section, patients with FD have on an average significantly larger antral area
      than healthy controls. METHODS: In this study we investigated the relationship
      between the antral area measured by ultrasound and the amount of fasting gastric
      content quantitated by aspiration through the gastroscope in 30 patients. In five
      healthy controls we measured the increment of the antral area after ingestion of
      graded volumes of water. All recordings were made in interdigestive phase I.
      RESULTS: Measurements of the antral area were highly reproducible, with small
      variations within an hour and from day to day. There was a highly significant
      correlation between ultrasonographically measured antral area and amount of
      fasting gastric juice and between increment of antral area and amounts of
      ingested water. CONCLUSIONS: The ultrasonographically measured antral area during
      fasting is highly reproducible. Enlarged fasting antral area reflects increased
      volume of gastric juice.

PMID- 7824857
TI  - Human gastric H,K-adenosine triphosphatase beta-subunit is a major autoantigen in
      atrophic corpus gastritis. Expression of the recombinant human glycoprotein in
      insect cells.
AB  - BACKGROUND: Sera from patients with atrophic corpus gastritis with pernicious
      anemia frequently contain parietal cell autoantibodies. We have previously
      demonstrated that the human H,K-adenosine triphosphatase (H,K-ATPase) alpha
      subunit constitutes a major autoantigen. The present study investigates whether
      the human H,K-ATPase beta-subunit is an autoantigen, too, METHODS: The gene of
      the human beta-subunit was expressed in insect cells by a baculovirus expression
      system. The reactivity of sera from 42 patients towards the recombinant
      glycoprotein was analyzed by means of an enzyme-linked immunosorbent assay.
      RESULTS: Thirty-nine of the 42 sera (93%) scored positive. Autoantibody binding
      in 41 sera (98%) was eliminated when unglycosylated beta-subunit was used as
      antigen, and antibody binding in the last serum was decreased by 30%.
      CONCLUSIONS: The results indicate that the beta-subunit is indeed a major
      autoantigen and that carbohydrates are involved in binding of the autoantibodies.

PMID- 7824858
TI  - Upper gastrointestinal hemorrhage. Comparison of the causes and prognosis in
      primary and secondary bleeders.
AB  - BACKGROUND: Hemorrhage from the upper gastrointestinal (UGI) tract is defined as
      primary when it is the cause of admission to hospital and as secondary when it
      complicates the course of patients admitted to hospital for other causes. The
      objective of this study was to compare the background features, course, and
      outcome of patients with primary and secondary bleeding. METHODS: All patients
      who underwent upper endoscopy because of acute UGI bleeding during 1988-91 in a
      tertiary care university hospital were studied longitudinally. The background
      features of primary bleeders (n = 321) were compared with those of secondary
      bleeders (n = 125). From the primary bleeders, a group was matched to the
      secondary bleeders by age, sex, use of nonsteroidal anti-inflammatory drugs
      (NSAIDs), and liver disease. The laboratory and endoscopic findings, hospital
      course, and mortality were compared in the two groups. RESULTS: Secondary
      bleeders were on the average 5 years older than primary bleeders and were
      significantly more likely to have ischemic heart disease, chronic lung disease,
      and chronic renal failure. Use of corticosteroids, H2 blockers, antacids, and
      anticoagulants in this group was significantly more prevalent, whereas the use of
      NSAIDs was similar in the two groups. The case-control analysis showed a similar
      distribution of the causes of bleeding in the two groups. However, rebleeding,
      endoscopic hemostasis, and complications were more frequent in secondary
      bleeders. The mortality in secondary bleeders was 28%, compared with 10% in
      matched primary bleeders, for a relative risk of 3.8 (p = 0.0002). CONCLUSION:
      Secondary hemorrhage is associated with an increased mortality, which is related
      to the underlying diseases and not to a difference in the causes of bleeding.

PMID- 7824859
TI  - Antroduodenal manometry in children and adults with severe non-ulcer dyspepsia.
AB  - BACKGROUND: Nonulcer dyspepsia is common in adults but has been recognized only
      recently in children. METHODS: We compared signs, symptoms, and antroduodenal
      motility findings in 34 children and 35 adults with severe nonulcer dyspepsia.
      RESULTS: Symptoms and signs were similar in the two groups. Ten children (29%)
      and one adult (3%) required tube feedings (p = 0.01). Abdominal surgery had been
      performed on 6 of 34 (18%) children and 18 of 35 adults (51%) (p < 0.01), without
      relief of symptoms. Esophageal manometry was abnormal in 5 of 23 (22%) children
      and 6 of 31 (19%) adults. Antroduodenal manometry was suggestive of neuropathy in
      25 children and 26 adults and of myopathy in 3 children and 2 adults. Absence of
      phase 3 of the migrating motor complex was found in 4 children and 17 adults (p =
      0.01). Antroduodenal manometry was normal in six children and seven adults.
      CONCLUSION: Signs, symptoms, and discrete manometric abnormalities of childhood
      nonulcer dyspepsia resembled those of adult nonulcer dyspepsia. Manometric
      findings in nonulcer dyspepsia resembled those reported in chronic intestinal
      pseudo-obstruction, suggesting that these conditions are on a continuum of
      enteric neuromuscular diseases.

PMID- 7824860
TI  - Effect of erythromycin administration on upper gastrointestinal motility in
      scleroderma patients.
AB  - BACKGROUND: Gastrointestinal involvement is frequent in patients with
      scleroderma. Erythromycin, a macrolide antibiotic, has been shown to accelerate
      gastric emptying in normal subjects and diabetic patients. The present study
      investigated the effects of acute erythromycin administration on gastric and
      gallbladder motility in patients with scleroderma and gastrointestinal
      involvement. METHODS: Twelve scleroderma patients and 14 healthy subjects were
      investigated. Each subject was investigated on 4 different days. Gastric and
      gallbladder emptying and gastric motility were determined by sonography and
      manometry, and the effect of 2 mg/kg/h erythromycin in fasted patients or after
      semisolid meal evaluated. RESULTS: The half-time of gastric emptying in response
      to semisolid meal was 121.3 +/- 14.0 min (SE) in scleroderma patients and 45.7 +/
      10.4 min in healthy subjects (P < 0.01). The peak of gallbladder emptying
      occurred later in scleroderma patients (95.0 +/- 5.0 min) than in healthy
      subjects (45.0 +/- 8.0 min) (P < 0.01). Erythromycin stimulated gastric and
      gallbladder motility in fasted subjects, as shown by manometry and sonography,
      and accelerated gastric and gallbladder emptying when administered immediately
      before the meal (P < 0.01). CONCLUSIONS: Erythromycin accelerates gastric and
      gallbladder emptying in scleroderma patients and might be helpful in the
      treatment of gastrointestinal motor abnormalities in these patients.

PMID- 7824861
TI  - Effect of acute Yersinia enterocolitica infection on intestinal barrier function
      in the mouse.
AB  - BACKGROUND: Yersinia enterocolitica is an important cause of diarrhea, but little
      is known about the underlying mechanisms. We therefore studied the impact of
      acute Y. enterocolitica infection on intestinal barrier function in a mouse
      model. METHODS: For this purpose CD-1 mice were infected with Y. enterocolitica
      (serotype 08; 6 x 10(7) viable bacteria), and alternating current impedance
      analysis was performed on days 1, 2, 3, 5, and 8 after infection. RESULTS: The
      infection resulted in a decrease in epithelial resistance from 18.0 +/- 0.9
      omega.cm2 (controls) to 12.1 +/- 0.5 omega.cm2 (day 1, p < 0.001), from which the
      animals recovered by day 5. To locate this loss in barrier function, the
      horizontal distribution of local conductances was measured by voltage scanning,
      yielding two results. First, conductance was homogeneously distributed across the
      chamber area, excluding erosions or ulcers among the gross surface area and
      favoring tight junction opening as the source of barrier dysfunction. Second, the
      conductance of villus tips was compared with that of the intervillus region
      (consisting of lateral villus walls plus crypts). On day 1 the former was
      increased by 74% and the latter by 18%. Then, two other mechanisms of diarrhea
      were tested, namely malabsorption and secretion. First, the increase in ISC after
      the addition of 3-O-methylglucose, representing Na(+)-glucose cotransport, was
      shown not to be impaired. Second, bumetanide-inhibitable ISC, representing
      electrogenic Cl- secretion, also did not differ between controls and infected
      animals. CONCLUSIONS: Our data show that epithelial barrier dysfunction plays a
      role in Y. enterocolitica infection, while Na(+)-glucose cotransport and
      electrogenic Cl- secretion are unaltered.

PMID- 7824862
TI  - The effect of ingested lactulose on absorption of L-rhamnose, D-xylose, and 3-O
      methyl-D-glucose in subjects with ileostomies.
AB  - BACKGROUND: We have previously shown that small oral doses of poorly absorbed
      solute can significantly reduce absorption of test sugars in normal volunteers.
      To confirm these results and investigate the underlying mechanism, the effects of
      lactulose on absorption of three test sugars in subjects with ileostomies were
      studied. METHODS: Ten fasted subjects with ileostomies ingested an isosmolar test
      solution containing 2.5 g 3-O-methyl-D-glucose, 5.0 g D-xylose, 1.0 g L-rhamnose,
      and 50 microCi 51Cr-labelled ethylenediaminetetraacetic acid together with a blue
      dye transit marker. Urine was collected for time periods of 0-5 h and 5-24 h, to
      measure excretion of absorbed sugars, and ileostomy effluent was saved from 0-5 h
      and from 5 h until blue dye transit marker was no longer present, to measure
      small-bowel output of unabsorbed sugars. After 1 week the test was repeated,
      including 5 g lactulose in the test solution. RESULTS: Inclusion of lactulose in
      the test solution significantly reduced the 5 h and 24 h urine excretion of L
      rhamnose and D-xylose but not that of 3-O-methyl-D-glucose and increased 0- to 5
      h and total ileostomy output of L-rhamnose and D-xylose but not of 3-O-methyl-D
      glucose. The presence of lactulose also reduced the time for first appearance of
      the blue dye transit marker in the effluent and increased effluent volume
      together with output of electrolyte. CONCLUSION: Poorly absorbed solute reduces
      intestinal absorption by retention of fluid and electrolyte, with subsequent
      intraluminal dilution and acceleration of transit.

PMID- 7824863
TI  - Carbohydrate malabsorption: quantification by methane and hydrogen breath tests.
AB  - BACKGROUND: Previous studies in small series of healthy adults have suggested
      that parallel measurement of hydrogen and methane resulting from gut fermentation
      may improve the precision of quantitative estimates of carbohydrate
      malabsorption. Systematic, controlled studies of the role of simultaneous
      hydrogen and methane measurements using end-expiratory breath test techniques are
      not available. METHODS: We studied seven healthy, adult methane and hydrogen
      producers and seven methane non-producers by means of end-expiratory breath test
      techniques. Breath gas concentrations and gastrointestinal symptoms were recorded
      at intervals for 12h after ingestion of 10, 20 and 30 g lactulose. RESULTS: In
      the seven methane producers the excretion pattern was highly variable; the
      integrated methane responses were disproportional and not reliably reproducible.
      However, quantitative estimates of carbohydrate malabsorption on the basis of
      individual areas under the methane and hydrogen excretion curves (AUCs) tended to
      improve in methane producers after ingestion of 20 g lactulose by simple addition
      of AUCs of methane to the AUCs of the hydrogen curves. Estimates were no more
      precise in methane producers than similar estimates in non-producers.
      Gastrointestinal symptoms increased significantly with increasing lactulose dose;
      correlation with total hydrogen and methane excretion was weak. CONCLUSIONS: Our
      study suggests that in methane producers, simple addition of methane and hydrogen
      excretion improves the precision of semiquantitative measurements of carbohydrate
      malabsorption. The status of methane production should, therefore, be known to
      interpret breath tests semiquantitatively. The weak correlation between hydrogen
      and methane excretion and gas-related abdominal complaints suggests that other
      factors than net production of these gases may be responsible for the symptoms.

PMID- 7824864
TI  - Water-soluble ethylhydroxyethyl cellulose: a new agent against bacterial
      translocation from the gut after major liver resection.
AB  - BACKGROUND: Bacterial translocation from the gut to extraintestinal sites has
      been demonstrated as a mechanism explaining bacterial infectious complications
      after various insults. METHODS: To explore the potential therapeutic value of
      water-soluble ethylhydroxyethyl cellulose (EHEC). Its effects on macrophage
      phagocytic capacity, bacterial adherence on the intestinal surface, and bacterial
      growth were evaluated both in vivo and in vitro. RESULTS: Preoperative
      administration of EHEC reduced the incidence of bacterial translocation from the
      gut to mesenteric lymph nodes and blood and prevented overgrowth by enteric
      bacteria after 70% or 90% hepatectomy. Uptake of macrophages harvested from blood
      decreased after intravenous administration of EHEC. EHEC diminished the otherwise
      increased bacterial adherence on the intestinal surface induced by major liver
      resection. EHEC in bacterial cultures for over 1 h was capable of inhibiting
      bacterial growth and delaying bacterial DNA synthesis in vitro. CONCLUSIONS: The
      present study indicates that EHEC could be a potential agent for the prevention
      of gut-origin sepsis.

PMID- 7824865
TI  - Hamartoma of Brunner's glands causing massive haematemesis.
AB  - BACKGROUND: Brunner's gland hamartomas are very uncommon lesions and are usually
      asymptomatic. METHODS: A 77-year-old man was urgently operated on for massive
      upper gastrointestinal bleeding, associated with haematemesis. RESULTS: A 3.5 x 3
      x 3 cm mass arising from the anterior aspect of the first part of the duodenum
      was found. Histologic examination showed groups of Brunner-type glands without
      atypia; these coexisted with heterotopic pancreatic acini and ducts. CONCLUSIONS:
      This is a very rare cause of massive upper gastrointestinal bleeding and may
      easily be confused with bleeding from a peptic ulcer.

PMID- 7824866
TI  - The relation between biliary lipids, nucleation time, and number of gallbladder
      stones after percutaneous gallbladder puncture.
AB  - BACKGROUND: Biliary lipids and nucleation time are increasingly of importance in
      the understanding of the cholesterol nucleation process in gallstone patients.
      METHODS: Biliary lipids, total lipid concentration (TLC), cholesterol saturation
      index (CSI) and nucleation time (NT) were studied in 221 bile samples from
      patients with solitary (n = 120) and multiple (n = 101) gallbladder stones.
      RESULTS: Biliary cholesterol concentration and CSI did not differ between
      patients with solitary or multiple stones; however, it was positively correlated
      with the CSI (r = 0.93; p < 0.01). We found a negative correlation between CSI
      and TLC (r = -0.77 for solitary stones and r = -0.79 for multiple stones; p <
      0.01). Furthermore, levels of total bile acids and phospholipids were similar in
      cases with solitary and multiple gallbladder stones. TLC did not correlate with
      single or multiple stones, whereas NT was determined to be negatively correlated
      with the number of gallstones (r = -0.39; p < 0.01). Patients with solitary
      stones had a significantly (p < 0.01) longer NT than those with multiple
      gallbladder stones (7.5 +/- 4.2 days versus 2.3 +/- 1.5 days). CONCLUSIONS: Our
      findings suggest that there exists a nucleation-promoting activity, which seems
      to be more pronounced in patients with multiple gallbladder stones than in those
      with solitary stones, indicating a major risk factor for the higher recurrence
      rate seen in these patients.

PMID- 7824867
TI  - Effects of hepatitis B virus antigens on interferon-gamma production of
      peripheral blood mononuclear cells from hepatitis B virus carriers and healthy
      individuals.
AB  - BACKGROUND: Although the precise mechanisms of persistent infection by hepatitis
      B virus are not yet known, several lines of studies suggest that hepatitis B e
      antigen in sera might modulate the immune response of the host. The aim of this
      study was to clarify the effects of hepatitis B virus antigen on cytokine
      production of lymphocytes. METHODS: We studied the effects of recombinant
      hepatitis B core antigen and surface antigen on interferon-gamma production of
      phytohemagglutinin-stimulated peripheral blood mononuclear cells from hepatitis B
      virus carriers and healthy individuals. Hepatitis B core antigen used in this
      study shared the antigenic site responsible for hepatitis B core and e antigen.
      RESULTS: Although pre-incubation of peripheral blood mononuclear cells with
      hepatitis B core/e antigen followed by stimulation with phytohemagglutinin
      significantly reduced the production of interferon-gamma, pre-incubation with
      hepatitis B surface antigen did not affect them. CONCLUSIONS: These results
      indicate that hepatitis B core/e antigen has the ability to inhibit interferon
      gamma production of lectin-stimulated peripheral blood mononuclear cells in
      vitro, suggesting that secretion of hepatitis B e antigen into sera might be how
      hepatitis B virus escapes the immuno-surveillance system of the host.

PMID- 7824868
TI  - Comparison of sequential and fixed-sample designs in a controlled clinical trial
      with laparoscopic versus conventional cholecystectomy.
AB  - BACKGROUND: The aim of this study was to compare a fixed-sample and a sequential
      design with regard to study duration, sample size, and medical results in a real
      life situation. METHODS: A randomized study comparing laparoscopic and
      conventional cholecystectomy was carried out with a fixed-sample design, parallel
      with a sequential design. The main variable was duration of postoperative
      convalescence. RESULTS: In the fixed-sample trial the necessary number of
      patients was calculated to be 72. The sequential trial was conclusive after
      inclusion of 24 patients and reduced the duration of the study from 43 to 18
      weeks. Additionally, the sequential trial reached the same conclusions as the
      fixed-sample trial in all the observed variables except for one. CONCLUSION: The
      present study indicates that sequential design should be used more frequently in
      clinical trials, to involve the smallest possible number of patients necessary to
      reach a conclusion.

PMID- 7824869
TI  - Relationship between peripheral portal blood flow and liver function in patients
      with liver cirrhosis. Pulsed Doppler ultrasonographic study.
AB  - BACKGROUND: The relationship between portal hemodynamics and liver function in
      patients with liver cirrhosis remains unclear. METHODS: Using pulsed Doppler
      ultrasonography, we investigated portal hemodynamics in the trunk and the
      intrahepatic peripheral vessels and its relation to liver function in cirrhotic
      patients. RESULTS: The portal blood flow in the right anterior branch (RAB) in
      cirrhotic patients (n = 40) was significantly lower (p < 0.01) than that in
      normal subjects (n = 40). In the cirrhotic patients the portal blood flow in the
      RAB was significantly correlated with the values of serum albumin, total
      bilirubin, cholesterol, cholinesterase, prothrombin time, and ICG R-15, and that
      in group C (Child's grading) was significantly decreased (p < 0.01) compared with
      that in group A. No such difference was found in the main portal vein, the right
      posterior branch, or the umbilical portion of the left portal vein. CONCLUSIONS:
      The decrease in blood flow in the RAB is closely related to the impairment of
      liver function in cirrhotic patients.

PMID- 7824870
TI  - Pharmacology of ursodeoxycholic acid, an enterohepatic drug.
AB  - The pharmacokinetics, metabolism, as well as the pharmacodynamic actions of
      ursodeoxycholic acid are reviewed and related to its physicochemical properties.
      Ursodeoxycholic acid is absorbed incompletely because of its low aqueous
      solubility. After absorption, it is conjugated with glycine or taurine and
      circulates with the endogenous bile acids. At usual doses (8-10 mg/kg/day), the
      pool of ursodeoxycholyl conjugates constitutes 30-60% of circulating bile acids.
      Ursodeoxycholic acid is metabolized by intestinal bacteriae to lithocholic acid
      which does not accumulate in the circulating bile acids because of efficient
      hepatic sulfation. Administration of ursodeoxycholic acid causes decreased
      cholesterol absorption, increased bile acid biosynthesis, and decreased biliary
      cholesterol secretion. Ursodeoxycholic acid is a choleretic agent, as all bile
      acids, but differs from other dihydroxy-bile acids in being non-cytotoxic because
      it has less affinity for membranes, and when present at micellar concentrations
      does not solubilize membranes. Chronic administration of ursodeoxycholic acid
      appears to increase canalicular transport.

PMID- 7824871
TI  - Treatment with Ursodeoxycholic Acid in Clinical Hepatology. Proceedings of a
      workshop. Goteborg, Sweden, 3-4 February 1994.

PMID- 7824872
TI  - Influence of ursodeoxycholic acid on biliary lipids.
AB  - The advent of bile acid therapy has shed some light on the mechanisms involved in
      determining bile lipid secretion. The administration of cholelytic bile acids
      results in a lowering of cholesterol percent molar and saturation index due to a
      reduction in cholesterol secretion. Studies carried out after administration of
      bile acids showed initially that biliary cholesterol secretion rates were
      dependent on the hydrophobic/hydrophilic balance of the prevailing bile acid
      present in bile. However, more detailed investigations showed that some bile
      acids (cholic and chenodeoxycholic acids) did not follow this rule because of the
      presence of other mechanisms involved in determining biliary cholesterol
      secretion and a possible link between cholesterol synthesis and biliary
      cholesterol secretion. Several different human models have been used in more
      recent studies to arrive at a better understanding of the mechanisms involved in
      determining bile lipid secretion: obese patients, obese patients in rapid weight
      loss, patients with non-familial hypercholesterolemia and primary biliary
      cirrhosis. The findings in these studies indicate how modifications in biliary
      lipid secretion can easily be induced when there are changes in the relative
      amounts of bile acids. These changes may bring about modifications in intestinal
      absorption, liver synthesis, and secretion of cholesterol and bile acids that
      could possibly lead to the formation of lithogenic bile and subsequently to
      cholesterol gallstones.

PMID- 7824873
TI  - Effect of ursodeoxycholic acid on hepatic cholesterol metabolism.
AB  - Oral administration of ursodeoxycholic acid (UDCA) renders bile unsaturated with
      cholesterol by reducing the hepatic output of cholesterol. Theoretically, several
      mechanisms may be of importance. In the present overview, the effect of treatment
      with UDCA on hepatic cholesterol metabolism is evaluated, in particular the
      influence on hepatic cholesterol synthesis, 3-hydroxy-3-methylglutaryl coenzyme A
      (HMG CoA) reductase activity, bile acid synthesis, 7 alpha-hydroxylation of
      cholesterol, and esterification of cholesterol--acyl coenzyme A: cholesterol
      acetyltransferase (ACAT) activity. It is apparent that UDCA treatment does not
      inhibit the hepatic HMG CoA reductase activity. Neither is ACAT activity or the
      cholesteryl ester content changed by UDCA. The catabolism of cholesterol to bile
      acids is unaffected or slightly increased during administration of UDCA. It is
      concluded that a stimulated degradation of cholesterol to bile acids may partly
      explain the decrease in hepatic secretion of cholesterol obtained during UDCA
      administration. It is suggested that the reduction in cholesterol absorption from
      the intestine seen during UDCA therapy may also be of importance.

PMID- 7824874
TI  - Effects of ursodeoxycholic acid on plasma lipids.
AB  - Interference with the enterohepatic circulation leads to changes in plasma
      lipoprotein metabolism. Thus, increased bile acid synthesis (such as after
      cholestyramine therapy or biliary diversion) stimulates hepatic triglyceride
      production and increases the number of low density lipoprotein (LDL) receptors in
      the liver. However, treatment with chenodeoxycholic acid reduces triglyceride
      production and appears to reduce LDL catabolism. Ursodeoxycholic acid therapy,
      which has minor effects on bile acid synthesis, results in relatively minor
      changes in lipoprotein metabolism. A tendency for lowered LDL cholesterol levels
      may be related to the fact that ursodeoxycholic acid interferes with the
      enterohepatic circulation of the normal bile acids, particularly when
      administered at a high dosage.

PMID- 7824875
TI  - Ursodeoxycholic acid treatment of cholesterol gallstone disease.
AB  - Bile acid dissolution therapy alone or in combination with extracorporeal shock
      wave lithotripsy continues to be a safe and effective non-surgical treatment for
      highly selected patients with cholesterol gallstone disease. Its disadvantages
      are the duration of drug treatment and potential stone recurrence. Its
      advantages, however, are non-invasiveness, low rate of morbidity, and lack of
      mortality. Considering the variety of options in modern gallstone therapy, the
      careful selection of treatment should be tailored to the individual patient's
      clinical and personal situation. This will involve the patient in the decision
      making process.

PMID- 7824876
TI  - Is primary biliary cirrhosis an autoimmune disease?
AB  - This review summarizes the experimental and clinical support for an autoimmune
      origin of primary biliary cirrhosis (PBC). Direct proof is lacking, but
      indications in favour of an immunologic destructive mechanism include the
      demonstration of antibodies and T cell clones with specificity for mitochondrial
      autoantigens, and the lymphocytic infiltration/destruction of small bile ducts
      similar to that of graft-vs-host disease and rejection. There is a weak
      association with other autoimmune diseases, but no clear HLA linkage. Spontaneous
      animal models for PBC are lacking, and immunization of animals with purified
      autoantigen does not result in typical disease. Anti-mitochondrial antibodies
      (AMAs) of M2 type are diagnostic of PBC, and are mainly directed against a
      functional, restricted epitope on the E2 subunit of the pyruvate dehydrogenase
      complex (PDC). PDC-E2 shows several similarities to other classical autoantigens.
      The pathogenic role of AMA remains elusive. Recent studies have shown that AMAs
      detect an antigenic epitope expressed on the luminal surface of biliary
      epithelium in PBC liver. The initial triggering event might represent a microbial
      infection (molecular mimicry), or an aberrant surface expression of a true
      autoepitope.

PMID- 7824877
TI  - Ursodeoxycholic acid therapy in primary biliary cirrhosis.
AB  - In a total of 1004 patients in 11 controlled trials, treatment with
      ursodeoxycholic acid (UDCA) 8-15 mg/kg bodyweight per day led to a decrease of
      pruritus in 30-60% of cases, a decrease in aminotransferases and cholestasis
      indicating enzymes in serum by 20-80%, and a decrease of serum bilirubin by 3
      40%. A statistically significant improvement in liver histology was found in only
      two of these studies; in three others there was a positive trend. In three more
      trials histology was not examined, and in three studies there was no improvement.
      In the four studies investigating the time elapsed before liver transplantation
      and the number of deaths, only one definitely found that this was prolonged by
      UDCA, although in two of the other three there was a positive trend. During
      treatment, UDCA constitutes 30-50% of the total bile acids in bile and serum;
      however, its influence on the toxic bile acids is debatable. Cholic acid
      decreases, but deoxycholic acid and chenodeoxycholic acid are reduced to a lesser
      degree. UDCA therapy has now been practiced for 12 years and all authors consider
      the treatment to be safe, but the mode of action of UDCA is still unknown.

PMID- 7824878
TI  - Etiology and pathogenesis in primary sclerosing cholangitis.
AB  - The etiology and pathogenesis of the inflammatory and fibrotic bile duct lesions
      characteristic of primary sclerosing cholangitis (PSC) is unknown, but several
      lines of evidence support the contention that genetic and immunologic factors are
      involved. There is an association with human leukocyte antigens (HLA) with an
      increased frequency of DR3, DR6, and DR2 positive haplotypes. DRB3*0101(DR52a) is
      the most strongly associated allele in some studies, but the HLA gene conferring
      the primary HLA associated susceptibility to PSC remains to be established. There
      is an aberrant expression of HLA class II antigens (DR and DP) on bile duct
      epithelial cells, with the potential to present antigens to the surrounding T
      lymphocytes. A defective suppressor T-cell function has been suggested in some
      studies. The patients may have elevated levels of circulating immune complexes,
      immunoglobulins, and non-organ-specific autoantibodies. Antibodies to perinuclear
      antigens (pANCA) are present in about 80% of cases. Increased metabolism of
      complement C3, reduced clearance of immune complexes, and increased concentration
      of biliary immune complexes have been found. The strong association between PSC
      and ulcerative colitis (UC) has not been explained. The detection of circulating
      IgG antibodies against a specific epitope shared by epithelial cells in the bile
      ducts and colon in about two-thirds of PSC patients may be of importance. Portal
      bacteremia secondary to a diseased bowel may possibly contribute to development
      of liver disease in UC. Viral infections and toxic and ischemic factors have also
      been implicated in the pathogenesis of PSC. In conclusion, PSC seems to occur in
      genetically predisposed individuals, mediated by immunologic mechanisms. The
      primary event triggering the disease development is, however, unknown.

PMID- 7824879
TI  - Ursodeoxycholic acid therapy in treatment of primary sclerosing cholangitis.
AB  - The beneficial effects of ursodeoxycholic acid (UDCA) in patients with primary
      biliary cirrhosis led to therapeutic trials with this bile acid for the treatment
      of PSC. In two prospective placebo-controlled trials, UDCA led to a significant
      improvement of AP, GGT, ALT, AST, and, in one study, also of serum bilirubin. In
      both studies liver histology improved significantly, mainly due to a decrease of
      cellular infiltrates in portal triads. Pruritus and fatigue improved in
      approximately one-third of the patients, but, compared to placebo, this effect
      was not significant. In a follow-up study after on average 3.1 years of UDCA
      treatment, 7/43 of the patients with stages I-IV disease developed a stenosis of
      the common bile duct which was effectively treated by endoscopic dilatations. Of
      57 patients with PSC included since 1987 in the study, 14 dropped out and of
      these in 10 information on the outcome is available. In patients treated by UDCA
      and, whenever necessary, by endoscopic dilatations, the frequency of
      transplantations was significantly reduced in comparison to patients who dropped
      out of the study. Bile duct carcinoma developed in 5% of our patients. The data
      indicate that treatment of patients with PSC with UDCA and by endoscopic
      dilatations of common duct stenoses is promising. In patients with endstage
      disease, the only effective therapy is liver transplantation. Therefore, the
      early diagnosis of the disease seems very important.

PMID- 7824880
TI  - A possible role of ursodeoxycholic acid in liver transplantation.
AB  - There are many different causes of graft dysfunction and cholestasis after liver
      transplantation. These include non-primary function, preservation and reperfusion
      injury, acute rejection, artery thrombosis, drug toxicity, bile leakage, and bile
      duct stenosis. Medication with ursodeoxycholic acid (UDCA) has beneficial effects
      in different cholestatic conditions. The initial rationale for its use after
      liver transplantation was to alter the bile acid pool to a more atoxic
      composition, as liver transplantation can be associated with cholestasis and can
      stimulate the initial bile production. We have consecutively treated 41 patients
      with primary graft function with UDCA. During the first postoperative month, 17%
      of the UDCA treated patients had an episode of acute rejection compared with 75%
      of a historical control group of 8 patients. The results suggest that adjuvant
      treatment with UDCA reduces acute liver graft rejection. This has to be confirmed
      by controlled prospective trials; one is presently being carried out in the
      Nordic countries. Several studies have indicated an immunomodulating capacity of
      this bile acid and we have recently reported our results from a heart transplant
      model in the rat, where treatment with UDCA prolonged graft survival. Improvement
      in surgical technique and postoperative care as well as immunosuppressive
      treatment has improved the results of liver transplantation. Acute rejection is
      nowadays a dominating problem after liver transplantation and the inclusion of
      UDCA may reduce morbidity.

PMID- 7824881
TI  - Cystic fibrosis. Is treatment with ursodeoxycholic acid of value?
AB  - Liver and biliary diseases are common complications in cystic fibrosis (CF) and
      may even be so severe that liver transplantation is indicated in cases with mild
      pulmonary disease. The most common complications are steatosis,
      fibrosis/cirrhosis, micro gallbladder, cholelithiasis, and sclerosing
      cholangitis. Ursodeoxycholic acid (UDCA) has been used in the treatment of
      gallstones and pathological liver function in CF. The effect on gallstones has
      been contradictory, and the effect on liver function tests has been shown to be
      dose-dependent. A significantly better effect has been shown on liver function
      tests during treatment over 1 year with doses of 15-20 mg/kg/day. Although
      supplementation with taurine did not further improve this effect, it has been
      used in many studies. The biliary bile acid pool was enriched by UDCA from about
      10% to 35-40%, but a similar increase was not seen in serum. We have studied the
      long-term effect of UDCA in 10 patients with liver fibrosis or cirrhosis and/or
      sclerosing cholangitis. Liver function and liver morphology examined on liver
      biopsies by both light and transmission electron microscopy (TEM) were followed
      for 2 years. Preliminary results of this study are encouraging. UDCA is an
      interesting drug which binds to the hepatocyte membranes, stabilizing membrane
      structure in in vitro experiments and increasing the bicarbonate excretion in
      bile in pigs. The mechanism of the effect of UDCA in CF might not only be an
      increased choleresis; further studies will focus on these aspects.

PMID- 7824882
TI  - Inborn errors of metabolism with consequences for bile acid biosynthesis. A
      minireview.
AB  - Five inborn errors with consequences for bile acid biosynthesis have been
      described: 7-dehydrocholesterol 7-reductase deficiency, 3 beta-hydroxysteroid
      delta 5-oxidoreductase/isomerase deficiency, 3-oxo-delta 4-steroid 5 beta
      reductase deficiency, sterol 27-hydroxylase deficiency (cerebrotendinous
      xanthomatosis), and peroxisomal disease(s) with absence of peroxisomes. Diagnosis
      and treatment of these very rare disorders are discussed. Bile acid therapy is
      important in most of these disorders and in the case of 3 beta-hydroxysteroid
      delta 5-oxidoreductase/isomerase deficiency and 3-oxo-delta 4-steroid 5 beta
      reductase deficiency such therapy may save the life of the affected cholestatic
      infant. In the case of sterol 27-hydroxylase deficiency, early treatment with
      chenodeoxycholic acid may prevent the development of progressive neurological
      dysfunction, dementia, and ataxia. In the latter three cases early diagnosis and
      treatment is of utmost importance.

PMID- 7824883
TI  - Characteristics of cytotoxic T lymphocytes directed to influenza virus
      haemagglutinin elicited by immunization with muramyldipeptide-influenza liposome
      vaccine.
AB  - We examined the characterization of the antiviral T lymphocytes elicited by
      immunization with a novel liposome vaccine (MDP-virosome) constructed with
      synthetic muramyldipeptide; [6-0-(2-tetradecylhexadecanoyl)-N-acetylmuramyl-L
      alanyl-D-isoglutamine] , cholesterol, influenza virus haemagglutinin and
      neuraminidase. The haemagglutinin glycoprotein first appeared to induce a
      significant subtype-specific cytotoxic activity through its arrangement on the
      inner and outer surfaces of the MDP-virosome. Splenocytes of BALB/c mice
      immunized with the virosome vaccine containing H3 haemagglutinin and N2
      neuraminidase from human Hong Kong virus markedly lysed H3N2 virus-infected
      target cells, but not those infected with virus possessing a different subtype
      such as H1N1 surface antigens. Exposure of these splenic lymphocytes to virus
      antigen in vitro further enhanced their cytotoxic activity. The cytotoxic
      lymphocytes generated by the MDP-virosome vaccine expressed Thy 1 and CD4
      antigens on their cell surface, and these activities were restricted by class II
      histocompatibility gene products. The marked reduction of pulmonary virus titres
      in infected mice caused by transferred immune spleen cells suggested that the MDP
      virosome vaccination is able to protect against influenza virus infection through
      enhanced cellular immune responses.

PMID- 7824884
TI  - Subpopulations of T lymphocytes in the peripheral blood, dermal lesions and lymph
      nodes of post kala-azar dermal leishmaniasis patients.
AB  - Distribution of different subpopulations of T cells in the dermal lesions, lymph
      nodes and peripheral blood of post kala-azar dermal lesihmaniasis (PKADL)
      patients was studied by using appropriate phenotypic markers for CD2+, CD4+ and
      CD8+ cells. Histopathological studies of skin lesions showed marginal to massive
      infiltration of mononuclear cells depending upon the duration of illness and type
      of lesions. Thus, while the hypopigmented patches were represented by small focal
      collections of lymphocytes with scanty parasites in the dermis, these were
      replaced at the nodular stage with massive granulomas consisting of lymphocytes,
      plasma cells and histiocytes with numerous amastigotes. The involvement of CD4+
      and CD8+ cell types in these lesions also showed a gradual change from the
      appearance of a few cells of both the phenotypes in early hypopigmented type to
      massive accumulation of cells, primarily of CD8+ phenotype, in the granuloma of
      nodular type. However, the observed preponderance of CD8+ cells at the lesion
      site of chronic PKADL patients is in contrast to their peripheral blood CD4+/CD8+
      cell ratio (1.9:1) which remained within the normal limits. Similar studies of
      lymph nodes from PKADL patients with lymphadenopathy revealed infiltration of the
      cortical areas by T cells which were more of CD8+ than CD4+ phenotypes. All these
      results document the involvement of CD8+ cells in leishmanoid lesions. Thus, it
      is likely that these cells, in association with appropriate subpopulations of
      CD4+ cells, play a profound role in the evolution of dermal pathology in PKADL.

PMID- 7824885
TI  - Enhancement of infectivity of a non-syncytium inducing HIV-1 by sCD4 and by human
      antibodies that neutralize syncytium inducing HIV-1.
AB  - Enhancement of virus infectivity after sCD4 treatment has been documented for
      SIVagm and HIV-2. It has been suggested that a similar phenomenon may play a role
      in HIV-1 infection. In the present study we have analysed biological activities
      of virus neutralizing polyclonal and monoclonal human antibodies and of sCD4,
      towards HIV-1 chimeras with envelope proteins derived from one donor, which
      display different biological phenotypes. The antibodies, which recognize the V3
      and/or the CD4 binding domains of the glycoproteins of these viruses and also
      sCD4 showed different levels of virus neutralizing activity toward the syncytium
      inducing HIV-1 strains. In contrast, they all dramatically enhanced the
      infectivity of an HIV-1 chimera with an envelope glycoprotein displaying the non
      syncytium-inducing phenotype. Given the relatively conserved nature of non
      syncytium-inducing HIV-1 surface glycoproteins early after infection, these data
      suggest a major role for antibody mediated enhancement of virus infectivity in
      the early pathogenesis of HIV-1 infection.

PMID- 7824887
TI  - Freshly isolated tumour-infiltrating T-lymphocytes have a high cytotoxic
      potential, as measured by their ability to induce apoptosis in the target cell.
AB  - To test if freshly isolated tumour-infiltrating lymphocytes (TIL) can induce
      apoptosis in a target cell, we have combined two previously described methods.
      Because TIL predominantly are T-lymphocytes, we have applied a redirected
      approach. When the target cells that express anti-human-CD3 monoclonal antibodies
      in their membranes bind to the T cell receptor-associated CD3-complex, signals
      are generated, which activate T cell effector mechanisms. This approach
      circumvents problems with MHC-restriction and allows for functional testing of
      all T cells, irrespective of their clonal specificity. In order to assay for
      induction of DNA fragmentation, we have labelled the target cell nuclei with
      [3H]thymidine. Upon harvesting fragmented DNA are washed away. Electrophoretic
      analysis of the fragmented DNA demonstrated the characteristic 'ladder' pattern,
      consistent with apoptosis. This rapid and simple assay monitors the capacity of
      different T cells to induce apoptosis in the target cell. It depends on
      intercellular interactions and clearly discriminates between different T cell
      subsets. With this assay we demonstrate the functional integrity of the cytotoxic
      effector arm of freshly isolated TIL.

PMID- 7824886
TI  - Cytokines and murine autoimmune encephalomyelitis: inhibition or enhancement of
      disease with antibodies to select cytokines, or by delivery of exogenous
      cytokines using a recombinant vaccinia virus system.
AB  - To examine the complex role of cytokines in the pathogenesis of actively induced
      murine EAE we measured the levels of a number of cytokines (IL-6, IFN gamma and
      TNF) in the spinal cord and CSF of mice with active experimental autoimmune
      encephalomyelitis (EAE) and found them all to be elevated. We next treated mice
      with antibodies to these three cytokines, which were over expressed in the CNS,
      to determine if they would alter disease and found the following: anti-IL-6 had
      no significant effect on disease, anti-IFN gamma exacerbated disease, and anti
      TNF either enhanced, had no effect or inhibited EAE depending on the antibody
      used. We then treated mice with exogenous cytokines, delivered using a
      recombinant vaccinia virus system, and found that the IL-6 and TNF virus
      constructs inhibited EAE whereas the IFN gamma construct had no effect on
      disease. Other cytokine recombinant viruses were also tested and it was found
      that the IL-1 beta, IL-2 and IL-10 viruses inhibited EAE while an IL-4 virus
      either had no effect or enhanced disease. We do not know the mechanism of action
      of the various cytokines in this system, but irrespective of the mechanism(s),
      this work clearly demonstrates that delivery of select cytokines using
      recombinant virus-cytokine constructs can provide a powerful means of down
      regulating experimental organ-specific autoimmune disease.

PMID- 7824888
TI  - Increased levels of antibodies to IFN-gamma in human and experimental African
      trypanosomiasis.
AB  - In African trypanosomiasis the occurrence of antibodies to interferon-gamma (IFN
      gamma) was studied in both humans and experimental rats. Sera from patients
      infected with Trypanosoma brucei gambiense showed increased levels of antibodies
      to IFN-gamma as compared with controls from the same regions in Africa. In
      Sprague-Dawley rats infected with Trypanosoma brucei brucei an early appearance
      of IFN-gamma-producing spleen cells was observed, followed by an increase in
      levels of antibodies against IFN-gamma in the sera. Previously, IFN-gamma has
      been found to play a crucial role in trypanosome infections in rats by promoting
      proliferation of Trypanosoma brucei brucei. The appearance of antibodies to IFN
      gamma in humans, as in rats, indicates that this cytokine is produced also in the
      human infection. Its parasitic growth-stimulating and pathophysiological effects
      on the organism may be reduced by the antibodies.

PMID- 7824889
TI  - Alteration of the immune response during cancer development and prevention by
      administration of a mycobacterial antigen.
AB  - It has been shown previously that A60, an antigen complex of Mycobacterium bovis
      BCG, triggers humoral and cellular immune reactions in vivo and lymphocyte
      dependent macrophage activation in vitro. In the present work, the ability of A60
      to prevent murine tumour development, in conjunction or not with irradiated
      isologous cancer cells, was explored with Taper liver tumour (TLT), a mammary
      derived neoplasm (EMT6), and Lewis lung carcinoma (3LL). Repeated injections of
      A60 prior to challenge reduced the incidence of EMT6 and 3LL solid tumours and
      increased life span. This effect was enhanced by simultaneous administration of
      gamma-irradiated cancer cells (80-100% suppression of EMT6 and 3LL tumour
      growth). In mice developing or rejecting tumours, the status of humoral and
      cellular immunity was evaluated by A60-based immunoassays. Tumor development was
      accompanied by a rapid decrease of both anti-A60 IgG titre in blood and A60
      triggered delayed hypersensitivity reactions. Moreover, A60-induced T lymphocyte
      proliferation and macrophage-dependent autologous cancer cell cytolysis declined
      progressively during the course of tumour growth. In case of successful
      immunotherapy, a pattern similar to that of unchallenged controls was observed.
      Our results suggest that A60 promotes cancer rejection via tumour infiltration by
      lymphocytes and macrophages activated by A60-specific T lymphocytes. An increased
      processing of tumour-specific antigens and activation of tumour-infiltrating
      lymphocytes is induced by administration of irradiated cancer cells in
      conjunction with A60.

PMID- 7824890
TI  - Intraembryonic haemopoietic cells and early T cell development.
AB  - T cell precursors in the chick embryo have been localized into the intraembryonic
      mesenchyme (IEM) and into the para-aortic region before the first wave of the
      thymic colonization on embryonic day (ED) 6,5-8. The cell surface markers of
      avian prethymic stem cells are not known. It is also not known whether these
      precursor cells are already committed to the T cell lineage before their thymic
      colonization. In 7-day-old chick embryos Ov+ cells were found in the para-aortic
      region. Also the endothelial cells of the embryonic dorsal aorta were positively
      stained. Ov antigen might represent a very primitive marker for precursor cells
      having the potentiality to differentiate both to haemopoietic and endothelial
      cells. Scattered CD45+ cells were observed in the same para-aortic area as in
      many haemopoietic areas in the loose embryonic mesenchymal tissues. CD8 alpha
      (MoAb 3-298) expressing haemopoietic cells were detected before thymic
      colonization on ED6. In flow cytometric analysis of IEM precursors Ov, CD45 and
      CD8 alpha expressing cells seemed to form distinct subsets suggesting
      heterogeneity of these haemopoietic cells.

PMID- 7824891
TI  - Requirement of CD4+ lymphocytes in IL-2-stimulated NK cell proliferation.
AB  - Growth requirements of human natural killer cells in IL-2-supplemented cultures
      were studied. NK cell proliferation was monitored by the MAC (morphology antibody
      chromosomes) technique and subset specific cell cycle analysis, which both enable
      direct determination of cell growth in specific lymphocyte subsets among
      heterogeneous lymphocyte populations. Our results show that even in the presence
      of saturating concentrations of IL-2, the proliferative capacity of purified
      CD16+ cells is quite low, but can be stimulated in a dose dependent manner by
      CD4+ cells. CD4+ cells could partially be replaced by IL-4 but not by various
      other commercially available cytokines. These results provide further evidence of
      the requirement of accessory stimuli in NK cell proliferation, and support the
      interpretation that NK cells have a direct regulatory role in specific T cell
      responses.

PMID- 7824892
TI  - Monocyte activation by tumour cells: a role for carbohydrate structures
      associated with CD2.
AB  - Monocytes/macrophages can kill tumour cells and mediate tumour-destructive host
      responses e.g. by releasing tumour necrosis factor-alpha (TNF-alpha). The
      underlying mechanisms of tumour cell recognition, however, are not clear.
      Previous work in our laboratory suggested that carbohydrate moieties associated
      with the T cell adhesion molecule CD2 of Jurkat cells induce TNF-alpha secretion
      by human monocytes. In this study we present data indicating that the stimulatory
      capacity for TNF-alpha secretion is confined to carbohydrate moieties of tumour
      cell CD2. Irradiated resting peripheral T cells did not display stimulatory
      activity in contrast to irradiated Jurkat cells although surface expression of
      CD2 was similar. Activated T cells, however, induced TNF-alpha production by
      monocytes via a CD2-independent mechanism. Only affinity purified CD2 prepared
      from Jurkat cells but not from non-transformed T cells activated monocytes to
      secrete TNF-alpha. This activation process was blocked by anti-CD2 antibodies.
      Neuraminidase and PNGaseF treatment of isolated CD2 inhibited the stimulatory
      capacity whereas pronase treatment did not. These data suggest that carbohydrate
      moieties containing sialic acid mediate stimulation of monocytes. Taken together,
      these results indicate a role for glycosylation patterns typical of tumour cells
      in the recognition process of tumour cells by monocytes/macrophages.

PMID- 7824893
TI  - Peptide mapping of bovine T-cell epitopes for the 38 kDa tuberculosis antigen.
AB  - Mycobacterium bovis infection in cattle continues to be a problem in several
      regions, partly due to inadequate diagnostic tests. The aim of this study was to
      use an experimental model of the natural disease to identify T-cell epitopes from
      the mycobacterial 38 kDa antigen as potentially specific diagnostic reagents. A
      panel of overlapping synthetic peptides (16-mers with a five-residue overlap)
      were produced from the published amino acid sequence. It was found that
      peripheral blood lymphocytes from at least three of four experimentally infected
      animals, which were considered to be in either Th1- or Th1/Th2-dominated stages
      of anti-mycobacterial immunity, proliferated in response to five epitopes
      (residues 1-27, 88-107, 122-138, 243-260 and 307-328). However, in vitro
      production of IFN-gamma was detected only in response to epitope 122-138,
      indicating a role in protective immunity. The peptides were not recognized by
      control, uninfected animals, but all epitopes showed various degrees of
      recognition by animals which were field reactors to intradermal tuberculin
      testing. Furthermore, epitopes 1-27, 88-107 and 122-138 were recognized by four
      breeds of cattle and by animals from separate herds, suggesting genetic
      permissiveness in recognition which would be essential in the development of a
      diagnostic test.

PMID- 7824894
TI  - Cathepsin B generates the most common form of amyloid A (76 residues) as a
      degradation product from serum amyloid A.
AB  - Amyloid A protein (AA), the chief constituent of reactive amyloid deposits, is
      derived from serum amyloid A (SAA) and most commonly corresponds to the amino
      terminal 76 residues (AA76). Digestion of recombinant human SAA1 with a lysosomal
      thiol protease, cathepsin B, and analysis of the products by SDS-PAGE and amino
      terminal sequencing revealed that AA76 was generated as a minor and transient
      degradation product. Digestion with neutrophil elastase generated intermediates
      different from AA76. This finding suggests that cathepsin B may play an important
      role in amyloid fibrilogenesis by converting SAA to AA.

PMID- 7824895
TI  - Cell-cycle kinetics of proliferating mouse B lymphocytes in vitro.
AB  - Resting mouse B lymphocytes were stimulated in vitro with lipopolysaccharide,
      Sepharose-coupled anti-kappa antibodies or a combination of the two. B
      lymphocytes stimulated with anti-kappa entered the cell-cycle with more rapid
      kinetics and at a higher frequency than did the corresponding cell population
      stimulated with lipopolysaccharide. Using cell cycle analysis after DNA staining
      combined with an M phase block, the cell-cycle kinetics of in vitro cultured B
      lymphocytes was studied. The labelling index of lipopolysaccharide stimulated B
      lymphocytes was 60% while that for anti-kappa Sepharose stimulated cells was 85%.
      The generation time of the actively cycling population from both types of
      cultures was constant and was of the order of 18 h. Thus, the fraction of B
      lymphocytes induced to proliferate in vitro varies depending on the stimulus,
      while the growth kinetics of the actively proliferating populations are
      remarkably constant.

PMID- 7824896
TI  - [Collaboration at the service of the practitioner].

PMID- 7824897
TI  - [Gingival hyperplasia of drug origin. A review of the literature].
AB  - The frequency of gingival overgrowth is increasing, due to the more and more
      frequent use of cyclosporin and calcium antagonists. Such lesions are the same as
      those known to occur in patients treated with phenytoin. They appear after a few
      months of treatment and are favoured by inflammation. Marginal gingiva starts to
      grow in excess, especially in the anterior region, and might end up covering the
      teeth entirely, with major occlusal problems. The hyperplasia occurs in about 50%
      of the phenytoin treated patients and in about 20% of those treated with
      cyclosporin or calcium antagonists. A genetic predisposition has been thought to
      be present in such susceptible people. However, no precise pathogenic pathway,
      possibly common for the three types of drugs, has been clearly proposed. As for
      therapy, the most severe lesions are treated by surgery but, in general, the
      dentist can be very helpful by simply stressing gingival hygiene.

PMID- 7824898
TI  - [Temporomandibular joint fractures in children. A clinical and radiological
      follow-up in 30 patients].
AB  - Disturbances of facial growth, occlusion and temporomandibular joint function
      respectively are all possible sequelae of condylar fractures in children. In this
      study 30 children (age at accident from 9 months to 14 years, mean 6 years and 9
      months) were reexamined who had sustained conservatively treated condylar
      fractures. Dysfunction and disturbances within the stomathognathic system were
      assessed by a clinical and radiographic examination. The mean interval between
      the accident and the follow-up study was 4 years and 11 months. The maximal
      interincisive distance was always better than 35 mm. The "en face" analysis
      revealed 6 cases with an inclined occlusion plane referring to the horizontal
      plane. Only 3 patients, all with bilateral condylar fractures, showed a
      restricted mandibular mobility. Remodelling of the condylar head was very good in
      77% of the cases. In the frontal plane, 21% of the unilateral cases and 33% of
      the bilateral cases respectively had a persistent medial inclination of the
      condyle. The measured difference in length of the processus articularis showed
      the highest correlation to the previous condylar fracture. The radiological
      evaluation after Ricketts (1960) and Mulick (1965) to assess facial asymmetry
      revealed six cases (20%) with a relevant angle difference of more than 5 degrees.

PMID- 7824899
TI  - [Mandibular hybrid dentures with 4 implants. An in-vitro stress analysis].
AB  - Four two-component implants (Bonefit) inserted in a mandibular model were fitted
      with various overdentures and then subjected to tension analysis using wire
      strain gauges. The implants were positioned between the mandibular foramina of
      the model; data were obtained for mesial, distal, lingual and buccal compressive
      and tensile loads of 50 N on duplicates of the prosthodontic base at the level of
      the first molar, using a measuring wire gauge. The greatest forces were
      registered for the secondary-splint telescope crown prosthesis; these forces were
      up to three times as high as the corresponding axial load. In the case of bar
      attachments, it is not so much the strain on the implant when the prosthesis is
      loaded that tends to cause problems, but rather the original process of screwing
      down the overdenture on insertion. During this process, the implants are
      subjected to forces so high that the use of a torque indicator is deemed to be
      indispensable as a clinical consequence of this finding. For similar
      considerations, a conditionally removable bar construction should not be removed
      during follow-up examinations. Magnetically retained dentures, by contrast,
      barely exert any tensile forces on the implants.

PMID- 7824900
TI  - [The quality appraisal of copy-milled complete-ceramic crown structures (Celay/In
      Ceram)].
AB  - In the present in vitro-study, the fitting accuracy on In-Ceram crown structures,
      produced by copy milling under the Celay system, is examined. A total of 32
      specimen was produced for four different stump forms (idealized incisor and
      premolar, each with a shoulder preparation or a 120 degree chamfer preparation)
      with indirect techniques. The data for the marginal gap ranged between 6 and 274
      microns. The shoulder preparation lead to significantly better fitting qualities
      than the 120 degree chamfer preparation. Median gaps were found at 44 microns
      (premolar) and 32 microns (incisor). Examinations under the scanning electron
      microscope showed a homogeneous structure of the sinter with a small variation of
      grain size and a compact particle packing. As far as the clinical application of
      In-Ceram crown structures, produced by copy milling, is concerned, a shoulder
      preparation with a rounded inner edge is recommended.

PMID- 7824901
TI  - [The extraction of retained mandibular wisdom teeth (I). The indications and
      preoperative diagnosis].

PMID- 7824902
TI  - [The extraction of retained mandibular wisdom teeth (II). The surgical technic,
      follow-up and complications].

PMID- 7824903
TI  - [Oral implantology--the clinical application of different implant systems. A
      report on the fall seminar of the Societe Suisse d'Implantologie Orale (SSIO) of
      30 September 1994 in Zurich].

PMID- 7824904
TI  - ["The objective is not to create a system of superdentists". Interview by Kurt
      Venner and Serge Roh].

PMID- 7824905
TI  - [Oral medicine at the end of the 20th century. A report on the Austrian Congress
      of Dentists at Graz 21 to 24 September 1994].

PMID- 7824906
TI  - ["Collaboration between societies of specialists is opening new prospects for
      continuing education". Interview by Kurt Venner and Serge Roh].

PMID- 7824907
TI  - [Austria: education in dentistry is evolving. Interview by Kurt Venner and
      Catherine Strahm].

PMID- 7824908
TI  - [The SSO is coordinating and conforming the education of dental assistants and of
      their apprenticeship instructors. A meeting of the Basic Education Working Group
      1 of the SSO Committee for the Nursing Team. Societe Suisse d'Odontoto
      Stomatologie].

PMID- 7824909
TI  - [Periodontics and Prosthodontics. A report on the joint Annual Meeting of the
      Swiss Society for Periodontics and of the Dental Prosthetics Society of
      Switzerland from 15 to 17 September 1994 in the Congress Center of Basel].

PMID- 7824910
TI  - [Interdisciplinary cooperation in surgical therapy. A report on the joint
      congress of the Union of Swiss Surgical Specialist Societies and of the Swiss
      Society for Maxillofacial Surgery in Lucerne from 22 to 24 September 1994].

PMID- 7824912
TI  - The great attractors. Chemical guides direct young neurons to their final
      destinations.

PMID- 7824913
TI  - Socializing with non-naked mole rats.

PMID- 7824911
TI  - For whom the bell curve really tolls. A tendentious tome abuses science to
      promote far-right policies.

PMID- 7824914
TI  - Seeing the cells that see.

PMID- 7824915
TI  - The prion diseases.

PMID- 7824916
TI  - The oldest old.

PMID- 7824918
TI  - Better than a cure.

PMID- 7824917
TI  - Egil's bones.

PMID- 7824919
TI  - "The Duesberg phenomenon": Duesberg and other voices.

PMID- 7824920
TI  - "The Duesberg phenomenon": Duesberg and other voices.

PMID- 7824921
TI  - "The Duesberg phenomenon": Duesberg and other voices.

PMID- 7824922
TI  - "The Duesberg phenomenon": Duesberg and other voices.

PMID- 7824923
TI  - Abnormal chromosome behavior in Neurospora mutants defective in DNA methylation.

PMID- 7824924
TI  - Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin's
      lymphoma.

PMID- 7824925
TI  - Malaria vaccine raises a dilemma.

PMID- 7824926
TI  - U.S.-Russian space science. Joint mission gets off to slow start.

PMID- 7824927
TI  - Biomedical ethics. Italian committee loses its balance.

PMID- 7824928
TI  - Biotech regulations. Germany loosens some red tape.

PMID- 7824929
TI  - Small spheres lead to big ideas.

PMID- 7824930
TI  - Zoology. St. Louis meeting showcases "creature features".

PMID- 7824931
TI  - Finis to MicroGeneSys saga?

PMID- 7824932
TI  - E-cadherin: a distant member of the immunoglobulin superfamily.

PMID- 7824933
TI  - Host range of a plant pathogenic fungus determined by a saponin detoxifying
      enzyme.
AB  - Antifungal saponins occur in many plant species and may provide a preformed
      chemical barrier to attack by phytopathogenic fungi. Some fungal pathogens can
      enzymatically detoxify host plant saponins, which suggests that saponin
      detoxification may determine the host range of these fungi. A gene encoding a
      saponin detoxifying enzyme was cloned from the cereal-infecting fungus
      Gaeumannomyces graminis. Fungal mutants generated by targeted gene disruption
      were no longer able to infect the saponin-containing host oats but retained full
      pathogenicity to wheat (which does not contain saponins). Thus, the ability of a
      phytopathogenic fungus to detoxify a plant saponin can determine its host range.

PMID- 7824934
TI  - Mechanisms of rhodopsin inactivation in vivo as revealed by a COOH-terminal
      truncation mutant.
AB  - Although biochemical experiments suggest that rhodopsin and other receptors
      coupled to heterotrimeric guanosine triphosphate-binding proteins (G proteins)
      are inactivated by phosphorylation near the carboxyl (COOH)-terminus and the
      subsequent binding of a capping protein, little is known about the quenching
      process in vivo. Flash responses were recorded from rods of transgenic mice in
      which a fraction of the rhodopsin molecules lacked the COOH-terminal
      phosphorylation sites. In the single photon regime, abnormally prolonged
      responses, attributed to activation of individual truncated rhodopsins, occurred
      interspersed with normal responses. The occurrence of the prolonged responses
      suggests that phosphorylation is required for normal shutoff. Comparison of
      normal and prolonged single photon responses indicated that rhodopsin begins to
      be quenched before the peak of the electrical response and that quenching limits
      the response amplitude.

PMID- 7824935
TI  - Measurement of lactose repressor-mediated loop formation and breakdown in single
      DNA molecules.
AB  - In gene regulatory systems in which proteins bind to multiple sites on a DNA
      molecule, the characterization of chemical mechanisms and single-step reaction
      rates is difficult because many chemical species may exist simultaneously in a
      molecular ensemble. This problem was circumvented by detecting DNA looping by the
      lactose repressor protein of Escherichia coli in single DNA molecules. The
      looping was detected by monitoring the nanometer-scale Brownian motion of
      microscopic particles linked to the ends of individual DNA molecules. This
      allowed the determination of the rates of formation and breakdown of a protein
      mediated DNA loop in vitro. The measurements reveal that mechanical strain stored
      in the loop does not substantially accelerate loop breakdown, and the
      measurements also show that subunit dissociation of tetrameric repressor is not
      the predominant loop breakdown pathway.

PMID- 7824936
TI  - Activation of RET as a dominant transforming gene by germline mutations of MEN2A
      and MEN2B.
AB  - Multiple endocrine neoplasia types 2A and 2B (MEN2A and MEN2B) and familial
      medullary thyroid carcinoma are dominantly inherited cancer syndromes. All three
      syndromes are associated with mutations in RET, which encodes a receptor-like
      tyrosine kinase. The altered RET alleles were shown to be transforming genes in
      NIH 3T3 cells as a consequence of constitutive activation of the RET kinase. The
      MEN2A mutation resulted in RET dimerization at steady state, whereas the MEN2B
      mutation altered RET catalytic properties both quantitatively and qualitatively.
      Oncogenic conversion of RET in these neoplastic syndromes establishes germline
      transmission of dominant transforming genes in human cancer.

PMID- 7824937
TI  - Solution structure of the epithelial cadherin domain responsible for selective
      cell adhesion.
AB  - Cadherins are calcium-dependent cell adhesion molecules containing extracellular
      repeats of approximately 110 amino acids. The three-dimensional structure of the
      amino-terminal repeat of mouse epithelial cadherin was determined by
      multidimensional heteronuclear magnetic resonance spectroscopy. The calcium ion
      was bound by a short alpha helix and by loops at one end of the seven-stranded
      beta-barrel structure. An exposed concave face is in a position to provide
      homophilic binding specificity and was also sensitive to calcium ligation.
      Unexpected structural similarities with the immunoglobulin fold suggest an
      evolutionary relation between calcium-dependent and calcium-independent cell
      adhesion molecules.

PMID- 7824938
TI  - Transcription factor ATF2 regulation by the JNK signal transduction pathway.
AB  - Treatment of cells with pro-inflammatory cytokines or ultraviolet radiation
      causes activation of the c-Jun NH2-terminal protein kinase (JNK). Activating
      transcription factor-2 (ATF2) was found to be a target of the JNK signal
      transduction pathway. ATF2 was phosphorylated by JNK on two closely spaced
      threonine residues within the NH2-terminal activation domain. The replacement of
      these phosphorylation sites with alanine inhibited the transcriptional activity
      of ATF2. These mutations also inhibited ATF2-stimulated gene expression mediated
      by the retinoblastoma (Rb) tumor suppressor and the adenovirus early region 1A
      (E1A) oncoprotein. Furthermore, expression of dominant-negative JNK inhibited
      ATF2 transcriptional activity. Together, these data demonstrate a role for the
      JNK signal transduction pathway in transcriptional responses mediated by ATF2.

PMID- 7824939
TI  - Wagnerian genetics.

PMID- 7824940
TI  - Clinicians catch top NIH officials' attention.

PMID- 7824941
TI  - Scientific misconduct. Federal panel recommends universities play bigger role.

PMID- 7824942
TI  - Smallpox. Virus wins stay of execution.

PMID- 7824943
TI  - Shedding light on blindness.

PMID- 7824944
TI  - Researchers broaden the attack on Parkinson's disease.

PMID- 7824945
TI  - The T cell receptor begins to reveal its many facets.

PMID- 7824946
TI  - An intelligent channel (and more).

PMID- 7824947
TI  - HIV population dynamics in vivo: implications for genetic variation,
      pathogenesis, and therapy.
AB  - Several recent reports indicate that the long, clinically latent phase that
      characterizes human immunodeficiency virus (HIV) infection of humans is not a
      period of viral inactivity, but an active process in which cells are being
      infected and dying at a high rate and in large numbers. These results lead to a
      simple steady-state model in which infection, cell death, and cell replacement
      are in balance, and imply that the unique feature of HIV is the extraordinarily
      large number of replication cycles that occur during infection of a single
      individual. This turnover drives both the pathogenic process and (even more than
      mutation rate) the development of genetic variation. This variation includes the
      inevitable and, in principle, predictable accumulation of mutations such as those
      conferring resistance to antiviral drugs whose presence before therapy must be
      considered in the design of therapeutic strategies.

PMID- 7824948
TI  - Structural basis for sugar translocation through maltoporin channels at 3.1 A
      resolution.
AB  - Trimeric maltoporin (LamB protein) facilitates the diffusion of maltodextrins
      across the outer membrane of Gram-negative bacteria. The crystal structure of
      maltoporin from Escherichia coli, determined to a resolution of 3.1 angstroms,
      reveals an 18-stranded, antiparallel beta-barrel that forms the framework of the
      channel. Three inwardly folded loops contribute to a constriction about halfway
      through the channel. Six contingent aromatic residues line the channel and form a
      path from the vestibule to the periplasmic outlet. Soaking of a crystal with
      maltotriose revealed binding of the sugar to this hydrophobic track across the
      constriction, which suggests that maltose and linear oligosaccharides may be
      translocated across the membrane by guided diffusion along this path.

PMID- 7824949
TI  - Zeta phosphorylation without ZAP-70 activation induced by TCR antagonists or
      partial agonists.
AB  - Small changes in the peptide-major histocompatibility complex (MHC) molecule
      ligands recognized by antigen-specific T cell receptors (TCRs) can convert fully
      activating complexes into partially activating or even inhibitory ones. This
      study examined early TCR-dependent signals induced by such partial agonists or
      antagonists. In contrast to typical agonist ligands, both an antagonist and
      several partial agonists stimulated a distinct pattern of zeta chain
      phosphorylation and failed to activate associated ZAP-70 kinase. These results
      identify a specific step in the early tyrosine phosphorylation cascade that is
      altered after TCR engagement with modified peptide-MHC molecule complexes. This
      finding may explain the different biological responses to TCR occupancy by these
      variant ligands.

PMID- 7824950
TI  - Cytostatic gene therapy for vascular proliferative disorders with a
      constitutively active form of the retinoblastoma gene product.
AB  - Vascular smooth muscle cell (SMC) proliferation in response to injury is an
      important etiologic factor in vascular proliferative disorders such as
      atherosclerosis and restenosis after balloon angioplasty. The retinoblastoma gene
      product (Rb) is present in the unphosphorylated and active form in quiescent
      primary arterial SMCs, but is rapidly inactivated by phosphorylation in response
      to growth factor stimulation in vitro. A replication-defective adenovirus
      encoding a nonphosphorylatable, constitutively active form of Rb was constructed.
      Infection of cultured primary rat aortic SMCs with this virus inhibited growth
      factor-stimulated cell proliferation in vitro. Localized arterial infection with
      the virus at the time of balloon angioplasty significantly reduced SMC
      proliferation and neointima formation in both the rat carotid and porcine femoral
      artery models of restenosis. These results demonstrate the role of Rb in
      regulating vascular SMC proliferation and suggest a gene therapy approach for
      vascular proliferative disorders associated with arterial injury.

PMID- 7824951
TI  - Molecular basis of the cauliflower phenotype in Arabidopsis.
AB  - Genetic studies demonstrate that two Arabidopsis genes, CAULIFLOWER and APETALA1,
      encode partially redundant activities involved in the formation of floral
      meristems, the first step in the development of flowers. Isolation of the
      CAULIFLOWER gene from Arabidopsis reveals that it is closely related in sequence
      to APETALA1. Like APETALA1, CAULIFLOWER is expressed in young flower primordia
      and encodes a MADS-domain, indicating that it may function as a transcription
      factor. Analysis of the cultivated garden variety of cauliflower (Brassica
      oleracea var. botrytis) reveals that its CAULIFLOWER gene homolog is not
      functional, suggesting a molecular basis for one of the oldest recognized flower
      abnormalities.

PMID- 7824952
TI  - Mutations of keratinocyte transglutaminase in lamellar ichthyosis.
AB  - Lamellar ichthyosis is a severe congenital skin disorder characterized by
      generalized large scales and variable redness. Affected individuals in three
      families exhibited drastically reduced keratinocyte transglutaminase (TGK)
      activity. In two of these families, expression of TGK transcripts was diminished
      or abnormal and no TGK protein was detected. Homozygous or compound heterozygous
      mutations of the TGK gene were identified in all families. These data suggest
      that defects in TGK cause lamellar ichthyosis and that intact cross-linkage of
      cornified cell envelopes is required for epidermal tissue homeostasis.

PMID- 7824953
TI  - Sex differences in regional cerebral glucose metabolism during a resting state.
AB  - Positron emission tomography was used to evaluate the regional distribution of
      cerebral glucose metabolism in 61 healthy adults at rest. Although the profile of
      metabolic activity was similar for men and women, some sex differences and
      hemispheric asymmetries were detectable. Men had relatively higher metabolism
      than women in temporal-limbic regions and cerebellum and relatively lower
      metabolism in cingulate regions. In both sexes, metabolism was relatively higher
      in left association cortices and the cingulate region and in right ventro
      temporal limbic regions and their projections. These results are consistent with
      the hypothesis that differences in cognitive and emotional processing have
      biological substrates.

PMID- 7824954
TI  - Cloning of an intrinsic human TFIID subunit that interacts with multiple
      transcriptional activators.
AB  - TFIID is a multisubunit protein complex comprised of the TATA-binding protein
      (TBP) and multiple TBP-associated factors (TAFs). The TAFs in TFIID are essential
      for activator-dependent transcription. The cloning of a complementary DNA
      encoding a human TFIID TAF, TAFII55, that has no known homolog in Drosophila
      TFIID is now described. TAFII55 is shown to interact with the largest subunit
      (TAFII230) of human TFIID through its central region and with multiple activators
      -including Sp1, YY1, USF, CTF, adenoviral E1A, and human immunodeficiency virus
      type 1 Tat proteins--through a distinct amino-terminal domain. The TAFII55
      interacting region of Sp1 was localized to its DNA-binding domain, which is
      distinct from the glutamine-rich activation domains previously shown to interact
      with Drosophila TAFII110. Thus, this human TFIID TAF may be a co-activator that
      mediates a response to multiple activators through a distinct mechanism.

PMID- 7824955
TI  - TH2 downregulation of macrophage HIV-1 replication.

PMID- 7824956
TI  - Binding of fluorescent-labeled low molecular mass heparin to latex microspheres
      and to rat and human leukocytes.
AB  - Fluorescent-labeled LMMH may be used to investigate the pharmacokinetics of
      heparins. FITC has been specifically bound by endpoint attachment to LMMH
      tyramine. In the present article two in vitro methods are described with the
      intention of developing new ex vivo test systems. To determine the concentration
      of heparin, protamine has been bound to the surface of magnetic latex particles.
      LMMH-tyramine-FITC bound dose dependently in a linear range from 0.1 to 30
      micrograms/mL to the protamine-coated latex particles. The fluorescence intensity
      of the latex particles was analyzed using flow cytometry. No differences in the
      dilution curves were observed between buffer system, rat and human plasma. This
      indicated that no interference of heparin binding took place with plasma proteins
      with respect to the binding to protamine. In the second method the binding of
      LMMH-tyramine-FITC on rat and human leukocytes was analyzed using flow cytometry.
      LMMH-tryamine-FITC bound dose dependently to rat and human granulocyes,
      monocytes, and lymphocytes. A linear relationship of binding was obtained for all
      three cell lines; the sensitivity was 0.1 microgram/mL for monocytes and
      lymphocytes and 0.03 microgram/mL for granulocytes without differences between
      rat and human cells. The data demonstrate a dose-dependent binding of LMMH
      tyramine-FITC to protamine coated latex beads and to rat and human leukocytes.

PMID- 7824957
TI  - Competitive binding of low molecular mass heparin-tyramine fluorescein-5
      isothiocyanate and unlabeled glycosaminoglycans to leukocytes.
AB  - Antithrombotic, antiarteriosclerotic, and anti-inflammatory actions of heparins
      may be mediated by binding of heparin to leukocytes. To get the first information
      on this hypothesis, fluorescein-labeled LMMH-tyramine has been used (LMMH
      tyramine-FITC) to analyze the binding of GAGs to lymphocytes, monocytes, or
      granulocytes. The fluorescence intensity on leukocytes was quantified by flow
      cytometry analysis. LMMH-tyramine-FITC bound dose dependently to lymphocytes,
      monocytes, and granulocytes. PE-labeled CD 11c antibodies identified the
      specificity of the binding of LMMH-tyramine-FITC to granulocytes. UFH and LMMH
      displaced LMMH-tyramine-FITC dose dependently from leukocytes. Equimolar ratios
      of LMMH and LMMH-tyramine-FITC revealed a 50% displacement of the labeled
      compound, indicating the specific binding by the polysaccharide chain. The
      synthetic pentasaccharide was 10-fold and dermatan sulfate 100-fold less
      effective than UFH in displacing LMMH-tyramine-FITC from leukocytes. The data
      indicate that negatively charged GAGs bind to the surface of lymphocytes,
      monocytes, and granulocytes. By decreasing the number of negatively charged
      groups of GAGs, the binding to the surface of leukocytes is decreased. The data
      obtained with the synthetic pentasaccharide indicate a binding of GAGs to the
      surface of leukocytes, independently of AT III. The cellular binding of heparins
      may significantly contribute to its antithrombotic and other biologic activities.

PMID- 7824958
TI  - Interaction between glycosaminoglycans, platelets, and leukocytes.

PMID- 7824959
TI  - Effects of heparin and its desulfated derivatives on leukocyte-endothelial
      adhesion.
AB  - The effect of heparin and partially desulfated heparin derivatives on thrombin
      and PAF-induced adhesion of PMNs to the endothelium was studied either by a
      fluorescence image analysis or by 111In-labeled PMNs. The results observed with
      these two techniques consistently indicated that heparin and O-des-heparin
      inhibited PMN adhesion in a dose-dependent manner. Moreover, N-des-Hep and N-O
      des-Hep, even if less effective, also inhibited the adhesion of PMNs when used at
      high concentrations. The effect of heparin and heparin derivatives was not
      directed to endothelial cells but rather to PMNs, as shown by the absence of
      inhibitory effects, when heparins were preincubated with endothelium.

PMID- 7824960
TI  - Pharmacological activity of a low molecular weight dermatan sulfate (desmin) in
      healthy volunteers.

PMID- 7824961
TI  - Plasma thrombin neutralization assay: pharmacokinetic applications.
AB  - UFH and its derivatives, LMWHs, are effective and safe in the prevention and
      treatment of DVT. The mechanism for this effectiveness has been difficult to
      explain, given that the anti-IIa activity of LMWHs is important for their
      antithrombotic activity and the reported half-life of the anti-IIa activity of
      LMWHs is very short. The standard chromogenic anti-IIa assay is performed in an
      artificial system consisting of highly diluted plasma to which antithrombin III
      is added. It is possible, therefore, that the apparently short half-life of the
      anti-IIa activity is dependent on the limitations of the anti-IIa assay, commonly
      used in the pharmacokinetic studies. We have developed an anti-IIa assay that is
      more sensitive than the standard one. Our assay is based on the ability of UFH or
      LMWHs to catalyze the formation of TAT complexes. PTNA was able to detect in
      vitro the anti-IIa activity produced by 0.01 anti-Xa IU/mL of UFH or 0.05 anti-Xa
      IU/mL of LMWHs. Ex vivo, it was able to describe the time course of plasma anti
      IIa activity of very low doses of UFH (intravenous or subcutaneous) or LMWHs. To
      characterize better the role of the anti-IIa activity of LMWHs, the
      pharmacokinetic properties of two of these agents have been evaluated in humans,
      assessing the anti-IIa activity by PTNA. Fraxiparine, 7500 and 10,000 ICU, and
      Enoxaparine, 20 and 40 mg, were administered subcutaneously to six healthy
      volunteers.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7824962
TI  - Oligo-heparin action on endogenous glycosaminoglycans. Pharmacokinetics: direct
      and mediated effects.

PMID- 7824963
TI  - Human pharmacokinetics of glycosaminoglycans using deuterium-labeled and
      unlabeled substances: evidence for oral absorption.
AB  - In the present study, the pharmacokinetics of extractive GAGs used as therapeutic
      agents have been studied after intravenous and oral administration on volunteers.
      The use of native or deuterium-labeled compounds, followed by HPLC/MS detection,
      allowed the quantitation of exogenous heparin and DS as major disaccharide
      fragments, obtained either by enzymatic or chemical depolymerization. In
      particular the high level of labeling reached in DS allowed its differentiation
      from structurally related endogenous species. The estimated plasmatic
      bioavailability was about 18% for DS. Notwithstanding the impossibility of
      evaluating the same parameters for heparin species, due to the interferences of
      endogenous GAGs, the results obtained provided clear evidence of oral
      availability of heparin and DS through detection and quantitation of structures
      specifically related to these GAGs. Due to the selectivity of the lyases used,
      the enzymatic degradation specifically allowed the detection of both DS and
      heparin species still retaining the original sulfation pattern. Additionally, the
      chemical degradation could detect the main metabolites of the drugs, consisting
      of partially to totally desulfated GAGs showing a more or less marked reduction
      in their molecular weight.

PMID- 7824964
TI  - Detection of the low molecular weight heparin component of ITF 1300 in urines
      after intranasal administration to dogs.
AB  - GAGs were purified from urine of dogs after intranasal administration of 40 mg/kg
      ITF 1300. The electrophoretic patterns of urine GAGs in acidic buffer showed the
      presence of heparin together with chondroitins, heparan sulfate, and hyaluronic
      acid. The heparin present in urines was purified using chondroitinase ABC, and
      its purity was tested by electrophoresis in acidic buffer. The sample obtained
      was characterized by 13C-NMR, showing the same characteristic signals of the
      heparin starting material.

PMID- 7824965
TI  - Organ glycosaminoglycan distribution after intravenous and oral administration in
      rats.

PMID- 7824966
TI  - Theoretical and experimental evidence on the use of glycosaminoglycans in BCG
      mediated immunotherapy of superficial bladder cancer.

PMID- 7824967
TI  - Metabolic changes associated with normal pregnancy and pregnancy complicated by
      diabetes mellitus.

PMID- 7824968
TI  - Screening and diagnosis of gestational diabetes.
AB  - A number of different recommendations have been made regarding screening and
      diagnostic testing for gestational diabetes. Although the ideal blinded study of
      the natural history of gestational diabetes has not been reported, nor has the
      perfect randomized clinical trial of various forms of treatment been performed,
      it seems likely that gestational diabetes has adverse effects on pregnancy
      outcome, and it is clear that this condition is a risk factor for subsequent
      diabetes. The problem remaining to be resolved is the precise level of glucose
      abnormality at which intervention may be beneficial. Once that is established,
      cost-benefit considerations can be applied to various screening recommendations.
      For the present, we have chosen to screen all pregnant women at 24 to 28 weeks
      gestation, using a 50-g, 1-hour oral glucose challenge. If the plasma glucose,
      determined in a standard laboratory analyzer using an enzymatic method, is
      greater than or equal to 130 mg/dL, a diagnostic 3-hour OGTT is recommended.
      Gestational diabetes is diagnosed based on thresholds outlined in Table 6. A
      survey by Landon and Gabbe in 1990 found that despite the ACOG recommendations,
      three fourths of generalist obstetricians and 90% of Maternal Fetal Medicine
      subspecialists report that they perform universal screening for gestational
      diabetes.

PMID- 7824969
TI  - Metabolic management of diabetes in pregnancy.

PMID- 7824970
TI  - Obstetric management of diabetes in pregnancy.

PMID- 7824971
TI  - Diabetic complications of diabetic pregnancies.

PMID- 7824972
TI  - Infant of the diabetic mother.

PMID- 7824973
TI  - Maternal implications of gestational diabetes.
AB  - Gestational diabetes encompasses a variable spectrum of decompensated glucose
      tolerance, with a substantial risk for developing future NIDDM. Several easily
      identifiable risk factors for subsequent diabetes have been identified, notably
      elevated fasting glucose levels during pregnancy, early diagnosis of gestational
      diabetes, and obesity. By continuing to identify independent risk factors during
      pregnancy and in the puerperium, we can develop better intervention programs and
      medical therapy to prevent or delay the onset of diabetes. Glucose tolerance
      testing in the postpartum period followed up by annual glucose surveillance for
      diabetes should be performed in all women with prior GDM. They should be actively
      educated about their high risk of diabetes and strongly encouraged to continue
      their diabetes and strongly encouraged to continue their diabetic diet, achieve
      an ideal body weight, and implement an exercise program. Combining such a program
      of preventive care with contraceptive visits contributes to a complete health
      care program for women with prior GDM during their reproductive years.

PMID- 7824974
TI  - Monitoring the effect of chemotherapy in Ewing's sarcoma of bone with MR imaging.
AB  - Magnetic resonance (MR) imaging was performed in 26 patients with Ewing's sarcoma
      of bone preceding and following neoadjuvant chemotherapy, to assess tumour
      response non-invasively prior to surgery. T1- and T2-weighted spin echo images
      were obtained. Changes including intra- and extramedullary signal intensities,
      tumour demarcation, tumour volume and the appearance of residual extramedullary
      tumour were compared with histopathology of the resected specimens. Reduction of
      tumour volume was significantly higher in good responders. Other single
      parameters did not correlate with histologic tumour response. However, when
      several MR parameters summarized in a classification system were combined, a
      positive correlation with histopathologic response was found. A limited decrease
      of tumour volume (< 25%) and/or residual soft tissue mass following chemotherapy
      correlated with a poor response. An inhomogeneous, well-defined cuff of abnormal
      tissue encircling the bone and/or radiological disappearance of the soft tissue
      tumour component following chemotherapy correlated with good response. Twenty
      three out of 26 patients were correctly classified by MR as good or poor
      responders. Minimal residual disease (< 10% of the entire tumour volume),
      observed histologically, could not be identified with MR imaging. Tumour volume
      reduction and residual extramedullary tumour, rather than changes of signal
      intensity, are major features for evaluating the response to chemotherapy in
      Ewing's sarcoma.

PMID- 7824976
TI  - Imaging features of maxillary osteoblastoma and its malignant transformation.
AB  - We report two cases of osteoblastoma, one of them an unusual case in a 32-year
      old woman in whom a maxillary tumor was confidently diagnosed as an osteoblastoma
      at the time of primary excision and subsequently transformed into an osteosarcoma
      7 years after the onset of clinical symptoms. The other patient developed
      osteosarcoma arising in the maxilla, which was diagnosed 3 years after the
      primary excision and is very suggestive of malignant transformation in
      osteoblastoma. We present the radiological features, including computed
      tomographic and magnetic resonance imaging studies, of this unusual event of
      transformed tumor and compare imaging features of benign and dedifferentiated
      counterparts of this rare tumor complex.

PMID- 7824975
TI  - Classification of histopathologic changes following chemotherapy in Ewing's
      sarcoma of bone.
AB  - A uniform classification of response to chemotherapy is essential to allow
      comparison of local effect and ultimate prognosis between different therapy
      schedules. We define a histological grading system for assessment of the response
      to chemotherapy in Ewing's sarcoma, based on the amount and architectural pattern
      of residual histologically viable-appearing tumour, the preferential sites of
      minimal residual tumour and the amount of tumour necrosis. Twenty-six consecutive
      patients with a biopsy-proven Ewing's sarcoma were treated with chemotherapy
      prior to surgery. The effect of chemotherapy was evaluated microscopically on the
      specimens obtained after surgery. Response to chemotherapy was classified as
      minimal or no effect (< 10% tumour necrosis), moderate effect (solid areas of
      remnant viable tumour), minimal residual disease, and no evidence of disease
      (100% tumour necrosis or well-vascularized fibrous tissue). The subperiosteal
      area in particular and, less frequently, soft tissues and intramedullary
      compartment were identified as sites of predilection for persistence of
      microscopic viable tumour foci, frequently depicted as pseudo-rosettes in a
      characteristic scattered pattern. Although it is not well known whether
      morphological viability of these residual clusters in Ewing's sarcoma indicates
      biological viability, accurate preoperative local staging, with special attention
      to preferential sites of residual viable tumour, is essential. The proposed
      grading system can be used to standardize assessment of chemotherapy in trials,
      and may serve as a standard for non-invasive monitoring of preoperative
      chemotherapy with magnetic resonance imaging.

PMID- 7824977
TI  - Magnetic resonance imaging of pseudomalignant osseous tumor of the hand.
AB  - Noninfectious, nonneoplastic reactive processes of the hand, such as myositis
      ossificans circumscripta, pseudomalignant osseous tumor of soft tissue, and
      florid reactive periostitis, appear similar radiologically and histologically and
      are often difficult to differentiate. Magnetic resonance (MR) findings in two
      such lesions are reported. The extensive reactive change in the extraosseous soft
      tissue and the bone marrow and the relatively small extent of ossification may be
      characteristic. Although low-grade infection and small osseous neoplasms with
      reactive changes, such as osteoid osteoma, may still remain possible causes, MR
      imaging provides essential evidence for including noninfective, nonneoplastic
      reactive processes of uncertain cause in the list of differential diagnoses.

PMID- 7824978
TI  - Variation in Cobb angle measurements in scoliosis.
AB  - In order to determine the reliability of the Cobb angle measurement as it is used
      in the clinical management of scoliosis, a methodological survey was carried out.
      In the measurement of a Cobb angle two phases can be distinguished: (a) the
      production of a spinal radiograph and (b) the measurement of the angle itself. In
      respect of the first phase, the variation in production of the radiographs was
      calculated on Cobb angle measurements made by one investigator on serial
      radiographs of patients who underwent spinal fusion for scoliosis and therefore
      had a fixed spinal curvature. For the second phase, the accuracy of Cobb angle
      measurement was investigated by comparing measurements on the same radiographs of
      46 scoliosis patients obtained by three investigators, namely two orthopaedic
      surgeons and an orthopaedic fellow who was assigned to a school screening
      project. Results were expressed as a Spearman correlation coefficient and a
      standard deviation of the differences. The Spearman correlation coefficient was
      0.98 for the repeated radiographs (production variation) and also 0.98 for the
      repeated measurements on one radiograph (interobserver measurement variation).
      The standard deviation of the differences in Cobb angle for the repeated
      radiographs amounted to 3.2 degrees and for the repeated measurements on one
      radiograph it was 2.0 degrees. Although there is a good reproducibility of the
      Cobb angle measurement between different investigators, the variation in
      production of a spinal radiograph is an important source of error. This should be
      taken into account when making decisions in scoliosis management.

PMID- 7824979
TI  - MR imaging of tibial collateral ligament injury: comparison with clinical
      examination.
AB  - We sought to clarify the capability of routine magnetic resonance (MR) imaging of
      the knee to detect and grade tibial collateral ligament (TCL) injury. We also
      wanted to define the exact MR findings that were the most important for
      diagnosis. Sixty-three patients were clinically evaluated for TCL injury prior to
      MR imaging of the knee on a 1.5-tesla system. MR studies were scored with respect
      to multiple direct and indirect findings. By discriminant analysis, the overall
      accuracy of classification (into clinical grades 1, 2, 3 and normal) on the basis
      of MR was 65%. Accuracy for detection of abnormal TCLs was 87%. The most useful
      MR findings for detection and grading of TCL injury were direct signs:
      subcutaneous edema over the TCL, focal disruption of the TCL, increased signal in
      the TCL on T2-weighted images, and longitudinal striations within the TCL.
      Indirect signs such as trabecular trauma were less useful for TCL evaluation. The
      presence of a tear of the anterior cruciate ligament, however, correlated with
      TCL injury of a higher grade. T2-weighted coronal images, by better depicting
      intraligamentous edema and fiber disruption, improved the MR assessment of the
      TCL.

PMID- 7824980
TI  - MR imaging of the accessory soleus muscle appearance in six patients and a review
      of the literature.
AB  - We examined seven ankles with an accessory soleus muscle to determine if the
      magnetic resonance (MR) imaging features were sufficient to allow accurate
      diagnosis of this anomalous muscle. We believe that the diagnosis of an accessory
      soleus muscle is unequivocal with MR imaging on the basis of morphology and
      signal intensity. Therefore, we suggest that this imaging method should be
      utilized in patients suspected of having a mass or with persistent swelling in
      the region of the ankle with or without pain, for the noninvasive diagnosis of
      this muscle and to better define the regional anatomy presperatively if surgery
      is being considered for relief of symptoms.

PMID- 7824981
TI  - Isolated subacromial bursal fluid on MRI of the shoulder in symptomatic patients:
      correlation with arthroscopic findings.
AB  - Fluid in the subacromial bursa (SAB) is a common finding on magnetic resonance
      (MR) images of the shoulder, and the implications of this finding have not been
      clarified. We retrospectively reviewed and correlated the MR features with
      arthroscopic findings in 21 symptomatic patients who had fluid in the SAB on MR
      imaging without demonstrable rotator cuff tear. Rotator cuff impingement was the
      most frequent surgical finding (42.9%). Other frequent surgical observations were
      glenoid labrum abnormality (28.6%), bursitis (19%), and supraspinatus tendinitis
      (14.3%). Distribution of acromial types was similar to that reported by Bigliani
      et al., and impingement was evenly distributed among acromial types in our study
      population. We conclude that in our patient population group the MR finding of
      isolated SAB fluid in symptomatic patients is highly likely to be associated with
      the finding of other abnormalities in the shoulder joint at surgery.

PMID- 7824982
TI  - Magnetization transfer contrast (MTC) and MTC-subtraction: enhancement of
      cartilage lesions and intracartilaginous degeneration in vitro.
AB  - Human articular cartilage from 16 cadaveric or amputated knees was studied using
      standard magnetic resonance imaging (MRI), on-resonance magnetization transfer
      contrast (MTC) and MTC-subtraction MRI. Results were compared with subsequent
      macroscopic and histopathological findings. MTC-subtraction and T2-weighted spin
      echo images visualized cartilaginous surface defects with high sensitivity and
      specificity. MTC and T2-weighted spin-echo images revealed intra-cartilaginous
      signal loss without surface defects in 80% of the cases, corresponding to an
      increased collagen concentration. It is concluded that MTC is sensitive to early
      cartilage degeneration and MTC-subtraction can be helpful in detecting cartilage
      defects.

PMID- 7824983
TI  - Diagnosis of partial and complete rotator cuff tears using combined gradient echo
      and spin echo imaging.
AB  - Most magnetic resonance (MR) studies evaluating the rotator cuff for tears have
      used T2-weighted imaging in the coronal oblique and sagittal oblique planes. T2*
      weighted gradient echo imaging, however, has advantages over spin echo imaging,
      including contiguous slices without cross-talk, high contrast around the cuff,
      and intrinsically shorter imaging times which can be used to increase the number
      of signals averaged and thus improve the signal-to-noise ratio. We reviewed the
      shoulder MR scans of 87 consecutive patients who underwent both a MR scan and a
      shoulder arthroscopy during which the size of tears, if present, was graded. The
      reviewers were blinded as to the history and arthroscopic results. The MR scans
      included oblique coronal T2*-weighted gradient echo and oblique sagittal T2
      weighted spin echo images. MR cuff grades were correlated with arthroscopic
      findings. For complete tears, the sensitivity of MR was 0.91 and the specificity
      0.95. For partial tears, the sensitivity was 0.74 and the specificity 0.87. This
      accuracy is similar to two-plane T2-weighted imaging as previously reported in
      the literature. There was a statistically significant correlation (p < 0.0005)
      between the cuff grade as determined by MR and the arthroscopic findings.

PMID- 7824984
TI  - Magnetic resonance imaging of hemochromatosis arthropathy.
AB  - This study was undertaken to compare plain film radiography and magnetic
      resonance imaging in the assessment of hemochromatosis arthropathy of the knees
      of ten patients with a biopsy-proven diagnosis. Both modalities enabled
      visualisation of bony degenerative changes; magnetic resonance imaging enabled
      additional visualization of deformity of both cartilage and menisci. Magnetic
      resonance imaging failed reliably to confirm the presence of intra-articular iron
      in the patients studied. No correlation was observed between synovial fluid
      magnetic resonance signal values, corresponding serum ferritin levels, or the
      severity of the observed degenerative changes.

PMID- 7824985
TI  - Vertebral pedicle diameter as determined by computed tomography: inaccuracies
      observed by direct measurement of cadaveric lumbar spine.
AB  - The isthmic diameter of the vertebral pedicle is an important dimension affecting
      the stability of transpedicular screwing. The isthmic diameter of the pedicle was
      measured in the lumbar spines of 18 Japanese cadavers (10 male, 8 female) by
      axial computed tomographic (CT) scan and directly with calipers. In L1 and L2,
      there was no significant difference between the average value of the isthmic
      diameter as determined by the two methods (Student's t-test). However, in L3-5,
      the average value of the isthmic diameter as determined by axial CT scan was
      significantly greater than that given by caliper measurement. In view of the fact
      that caudally the longitudinal axis of the pedicle diverges towards the mid-line
      of the vertebral body in the coronal plane, the plane of the CT scan cannot be
      parallel to the real isthmic diameter of the pedicle. Therefore, it is suggested
      that below L2 the diameter as determined by axial CT scanning is greater than the
      real isthmic diameter.

PMID- 7824986
TI  - The healed Segond fracture: a characteristic residual bone excrescence.
AB  - This report describes the natural history of the Segond fracture and documents
      the radiographic appearance of the healed Segond fracture. The clinical and
      radiographic records of 129 patients with acute anterior cruciate ligament (ACL)
      injuries were reviewed. Four (3.1%) of these patients had Segond fractures. On
      follow-up radiographic examination, seven patients demonstrated a characteristic
      bone excrescence arising 3-6 mm inferior to the lateral tibial plateau. In four
      of the five patients for whom acute injury films were available this excrescence
      arose at the site of the earlier Segond fracture. Healing of such fractures is
      associated with a characteristic bone excrescence distinct from an osteophyte.
      This excrescence implies significant internal derangement of the knee.

PMID- 7824987
TI  - Case report 847. Juxtacortical aggressive fibromatosis (desmoplastic fibroma) of
      the forearm.
AB  - A case has been presented of a 14-year-old male patient who developed a fusiform
      mass on the volar aspect of his left forearm following two fractures. Microscopic
      features and plain radiography, CT, and MRI appearance of juxtacortical
      aggressive fibromatosis are discussed.

PMID- 7824988
TI  - Case report 864. Elliptical, multicentric periosteal osteoid osteoma.
AB  - An extremely rare case of multicentric periosteal osteoid osteoma in a child was
      presented. The lesions were found to be embedded in a narrow elliptical strip,
      suggesting the possibility that lesional tissue was stretched in a longitudinal
      fashion as a result of the rapid skeletal growth. In young patients with
      stretched periosteal reaction who complain of pain, multicentric osteoid osteoma
      should be suspected. These nidi can be obscured by the exuberant periosteal
      reaction. Accurate evaluation of the radiographic findings is very important.

PMID- 7824989
TI  - Case report 865. Bacillary angiomatosis.
AB  - A case of bacillary angiomatosis was presented, characterized by subcutaneous
      lesions, systemic symptoms, and impressive periostitis which initially masked a
      small cortical lytic lesion. Review of the reported cases suggests that a
      diagnosis of bacillary angiomatosis should be strongly considered when
      periostitis is identified in an AIDS patient with skin lesions. Additionally,
      deep surgical biopsy of the skin lesion to include the subcutaneous tissue should
      be performed to confirm the diagnosis if the initial punch biopsies are
      unrevealing.

PMID- 7824991
TI  - Case report 867. Membranous lipodystrophy (polycystic lipomembranous
      osteodysplasia).

PMID- 7824990
TI  - Case report 866. Pseudotumor of the muscle associated with necrotizing vasculitis
      of medium- and small-sized arteries and chronic myositis.
AB  - A case of polymyositis and localized vasculitis presenting as a muscular
      pseudotumor of a lower extremity and periostitis several years after the onset of
      symptoms was reported and the MRI characteristics were described. This imaging
      modality demonstrated muscle signal abnormalities in several muscle groups and
      was useful in ruling out the presence of a mass and fatty degeneration of the
      muscle. The ability of the STIR sequence (Fig. 3D) to show muscle abnormalities
      and to allow fatty infiltration or degeneration to be ruled out has not been
      reported before in patients with vasculitic muscle involvement.

PMID- 7824992
TI  - Case report 868. Congenital bilateral spondylolysis and spondylolisthesis of the
      fourth cervical vertebra.
AB  - A case of congenital bilateral spondylolysis of fourth cervical vertebra was
      reported and the characteristic radiological features shown. Although the
      diagnosis is often suggested by the plain films, demonstration of the typical CT
      findings is often necessary to reach a final diagnosis. Awareness of this entity
      and its specific radiological features will help to differentiate this relatively
      benign cervical anomaly from other, more ominous, unstable causes of cervical
      spondylolisthesis such as those related to acute cervical injury. It may also
      prevent any inappropriate treatment from being undertaken.

PMID- 7824993
TI  - Case report 869. Benign metastasizing giant cell tumor of bone.
AB  - We presented a case of giant cell tumor of the sacrum with multiple pulmonary
      metastases in an 11-year-old girl. To the best of our knowledge, our patient is
      the youngest reported patient with a giant cell tumor with pulmonary metastases.
      Although giant cell tumor of bone with pulmonary metastases is extremely rare,
      this entity must be considered in the differential diagnosis of bone tumors.

PMID- 7824994
TI  - Case report 870. Schneckenbecken dysplasia, possibly a new variant.
AB  - We report the case of a newborn with a lethal newborn skeletal dysplasia, in whom
      skeletal and morphologic findings resembled those in schneckenbecken dysplasia
      except that the projection of bone from the medial aspect of the iliac bones,
      resembling the "snail's" head, was absent. This could be accounted for by
      variability or genetic heterogeneity.

PMID- 7824995
TI  - Case report 871. Synovial sarcoma, monophasic type.
AB  - A patient with a synovial sarcoma of the foot and several unusual radiographic
      findings has been reported. Radiographs demonstrated lamellated periosteal
      reaction in a metatarsal, a rare finding in cases of synovial sarcoma. Magnetic
      resonance scanning documented marrow invasion of multiple bones in the foot, when
      bony involvement has been reported as only erosive changes.

PMID- 7824997
TI  - Time for development of a regional disease information network?

PMID- 7824996
TI  - Case report 872. "Ancient" schwannoma (degenerated neurilemoma).
AB  - A case of an ancient schwannoma was presented. The rare occurrence of this tumor
      has resulted in only a few reported cases with descriptions of its features on
      imaging. Our patient's tumor, like one previously reported case, demonstrated
      calcification on the plain film - a finding not associated with other histologic
      types of schwannomas. Angiography revealed the tumor to be hypervascular.
      Evaluation by MRI demonstrated a lobulated, encapsulated soft tissue mass
      containing several cystic areas that corresponded histologically to areas of
      necrosis. Hypertrophied blood vessels were seen in the periphery of the tumoral
      mass. Too few ancient schwannomas have been reported to conclude whether or not
      radiographic evidence of soft tissue calcification is characteristic of this
      histologically distinctive subtype of schwannoma. However, since calcification is
      seen histologically as part of the degenerating process, its presence on plain
      films could be a feature of this tumor. Furthermore, the presence of cystic areas
      on MRI is not surprising given the pathological changes that occur in this tumor.
      We suggest that a diagnosis of ancient schwannoma be considered when a patient
      presents with a hypervascular soft tissue mass containing amorphous calcification
      on plain films and cystic areas on MRI. Despite the nonspecificity of these
      imaging findings, this point is relevant because each of these features suggests
      the presence of a malignant mass. Awareness of the possibility of a benign
      ancient schwannoma could obviate unnecessary radical surgery.

PMID- 7824998
TI  - AIDS related attitudes and sexual practices of the Jakarta WARIA (male
      transvestites).
AB  - As part of a community based educational campaign to convey the risk of HIV
      infection and AIDS to commercial sex workers in Jakarta, over 600 male
      transvestites (WARIA) were questioned about their sexual behavior patterns and
      their knowledge and attitude towards HIV infection and AIDS. Most expressed a
      genuine fear about AIDS, but they stated they did not have sufficient information
      to determine if their risk of infection, at this time, was great enough to
      command a change in their sexual conduct. Among the group who felt they were not
      at risk for HIV infection, 40% had 8 or more different sex partners per week. Low
      risk receptive oral sex, thigh massage (simulated vaginal sex) and masturbation
      of the client were routine activities but high risk receptive anal sex without
      condoms was most common. Despite such high risk behavior, the WARIA community
      remains free of HIV infections. However, if they refuse to accept the endorsement
      of their peer leaders and they fail to alter their sexual behavior because of an
      unawareness of their risk, that status will change soon.

PMID- 7824999
TI  - Bacterial meningitis in children: etiology and clinical features, an 11-year
      review of 618 cases.
AB  - During the period January 1980 to December 1990 (11 years) a retrospective study
      of patients with bacterial meningitis who were admitted to Bangkok Children's
      Hospital was carried out. There were 618 patients with 77 cases (12.5%) occurring
      below the age of one month (neonatal meningitis), and 541 cases (87.5%) between
      one month to 15 years (childhood meningitis). Pseudomonas aeruginosa was the most
      common pathogenic organism (16.9%) in neonatal meningitis; other causative agents
      in this age group included Klebsiella pneumoniae (13.0%), group B Streptococcus
      (11.7%), Escherichia coli and Enterobacter sp (10.4% each). In childhood
      meningitis, Haemophilus influenzae was the most common causative organism
      (42.3%), and followed by Streptococcus pneumoniae (22.2%) and Salmonella sp
      (12.4%). Excluding a 13 year-old leukemic patient, Salmonella meningitis occurred
      exclusively in infants, 87% of them were under six months, and 13% of them
      developed relapsing meningitis. Presenting symptoms and signs on admission of
      neonatal meningitis such as fever (81.8%), convulsions (45.4%), neck stiffness
      (22.5%), bulging fontanelle (33.3%) and Brudzinski sign (11.5%) were
      significantly less frequent than in the patients beyond the neonatal period (p <
      0.05). The overall fatalities during 1980-1990 were 45.4% and 17.3% for neonatal
      meningitis and childhood meningitis, respectively. The fatalities of the two age
      groups declined significantly during 1987-1990 to 26.3% and 11.4% respectively.

PMID- 7825000
TI  - A symposium on containment of mefloquine-resistant falciparum malaria in
      Southeast Asia with special reference to border malaria.
AB  - Important questions related to the factors responsible for and contributing to
      the origin and spread of multi-drug resistant falciparum malaria at the Thai
      Cambodian and Thai-Myanmar border areas are discussed, including the current
      geographical distribution of multi-drug resistance and the prevention and control
      of this phenomenon. Specific recommendations are made on epidemiological
      surveillance, drug deployment, vector control, and the problem of migration which
      plays a major role in the dissemination of resistant parasite populations. The
      recent advent of mefloquine resistance of P. falciparum in Thailand may serve as
      fair warning in the absence of stern measures for preventing the occurrence of
      resistance to the next and currently last line of antimalaria drugs, especially
      those with a long half-life, in areas with intensive, uncontrolled malaria
      transmission, such as tropical Africa.

PMID- 7825001
TI  - Increasing prevalence of antimicrobial resistance among organisms isolated from
      blood culture in a Singapore hospital.
AB  - The blood culture isolates obtained over the period 1985-1990 in a general
      teaching hospital were reviewed to determine trends in the prevalence of
      resistance to antimicrobial drugs. The percentages of Staphylococcus aureus
      isolates resistant to methicillin increased each year. Resistance among coagulase
      negative staphylococci also increased in prevalence: by 1990 approximately 50% of
      such isolates were resistant to methicillin, erythromycin, co-trimoxazole and
      gentamicin, 24% were resistant to clindamycin, 20% to fucidic acid but only 0.5%
      to vancomycin. Isolates of Enterobacteriaceae, excluding community-acquired
      salmonellae, showed increasing prevalence of resistance to beta-lactams, as did
      Acinetobacter spp isolates to gentamicin, co-trimoxazole and ceftriaxone. The
      isolates of Pseudomonas aeruginosa were exceptional, having no evident increase
      in the prevalence of resistance during the period. The rapid increases observed
      in relation to the other pathogens indicate the need for an antibiotic policy
      based on continuous surveillance of susceptibility patterns in the hospital.

PMID- 7825003
TI  - Prenatal tetanus immunization and other practices associated with neonatal
      tetanus.
AB  - The relationship between neonatal tetanus (NT) on one hand, and maternal tetanus
      immunization and other prenatal and natal practices on the other hand, was
      examined in a case-control study done at San Lazaro Hospital (SLH) in Manila from
      late 1990 to mid 1991. Included as cases were 54 patients diagnosed as NT on the
      basis of WHO criteria, and 50 controls who were patients 0-4 months of age,
      hospitalized at SLH during the study period and with no past history of tetanus.
      The result showed that the following were statistically associated with the risk
      of NT: home delivery (OR = 30.5); delivered by a traditional birth attendant (OR
      = 5.2); use of instrument other than scissors to cut the cord (OR = 19.3);
      traditional birth attendant who dressed the cord (OR = 12.7); and having less
      than two doses of tetanus toxoid (OR = 15.3). The need to intensify prenatal
      tetanus immunization, health education of the mothers as well as the training of
      birth attendants is evident from this study if NT has to be prevented.

PMID- 7825002
TI  - Upper airway carriage by Haemophilus influenzae and Streptococcus pneumoniae in
      Australian aboriginal children hospitalised with acute lower respiratory
      infection.
AB  - When nasopharyngeal secretions from 171 Australian Aboriginal children
      hospitalized with acute lower respiratory tract infections (ALRI) were cultured
      selectively for Streptococcus pneumoniae and Haemophilus influenzae, 136 (79.5%)
      and 151 (88.3%) children yielded 166 and 254 isolates of S. pneumoniae and H.
      influenzae, respectively. In colonized subjects multiple populations of S.
      pneumoniae (20% of carriage-positive patients) and H. influenzae (55%) were
      common. Pneumococci belonging to 27 types or groups were identified. H.
      influenzae serotype b colonized 16.4% of all children studied. More than one half
      of 152 children tested were excreting antibiotics at the time of admission to
      hospital. Significantly fewer children with serum antibiotic residues were
      colonized with S. pneumoniae than were antibiotic free children. Antibiotic usage
      had no measurable impact on the isolation rate of H. influenzae.

PMID- 7825004
TI  - Serogroup distribution and antimicrobial susceptibility of beta-hemolytic
      streptococci in clinical isolates.
AB  - Three hundred and four strains of beta-hemolytic streptococci were isolated from
      different patients at Siriraj Hospital during 1989-1990. Among these strains,
      24.01% were group A, 23.03% were group B, 2.96% were group C, 29.61% were group
      D, 0.66% were group F, 6.25% were group G and 13.48% could not be grouped by
      using the Lancefield reference method. The distribution of each serogroup
      according to the types of clinical specimens was also studied. From pus, group A
      Streptococcus (44.8%) was the most frequent isolate. From vagina/cervix/urethra
      specimens, group B Streptococcus (47.95%) was the most frequent isolate. From
      urine, group D Streptococcus (82.5%) was the most frequent isolate. From blood,
      group B Streptococcus (43.33%) was the most frequent isolate. From throat/sputum
      specimens, only group A Streptococcus was isolated. There were some differences
      in susceptibility to 19 antimicrobial agents among various groups of
      streptococci. Resistance to penicillin was not found in groups A, B, C, F and G
      streptococci except for group D (91.1% resistance for enterococci and 33.3%
      resistance for non-enterococci) and nongroupable streptococci (12.2% resistance).

PMID- 7825005
TI  - Recurrence of yaws outbreak in Thailand, 1990.
AB  - In November 1990, an outbreak of yaws was reported in a rural village of southern
      Thailand. A survey consisting of history taking, physical examination and blood
      tests for VDRL and TPHA was undertaken in the whole village and in the primary
      school of the village. A yaws case was defined as a person who had a positive
      VDRL confirmed by TPHA without history of other treponemal infection or post
      treatment of yaws. Fifty-four cases, an attack rate of 23%, were found in the age
      range from 2 to 79 years old. The epidemic curve started with a few cases in 1989
      and early 1990 with an increasing number of cases from June, and reached its peak
      in November. Half of the cases (53.7%) were children under 15 years. Male cases
      were higher than female (1.5:1). A survey of 105 primary school students found an
      attack rate of 32% (34/105) and the prevalence was higher in younger classes.
      Benzathine penicillin injection was given to cases for treatment. From this
      investigation, the Ministry of Public Health was alerted about the recurrence of
      yaws. Strengthening health education and surveillance activities was recommended
      in adjacent districts and provinces. The extent of the problem was assessed
      through surveys among school children and expanded to their family members if
      cases of yaws were found.

PMID- 7825006
TI  - Control randomized study of rehydration/rehydration with dioctahedral smectite in
      ambulatory Thai infants with acute diarrhea.
AB  - The study was performed to assess the efficiency, acceptability and safety of
      dioctahedral smectite (DS) associated with rehydration in ambulatory infants with
      acute diarrhea. Sixty-six Thai infants, aged 1-24 months were randomly divided
      into 2 groups. One group of 32 infants (control group) received oral or
      intravenous rehydration, the other group of 34 infants (DS group) received the
      rehydration with DS. Both groups were comparable for sex, age, weight, diet,
      duration of diarrhea, body temperature, nutritional and dehydration status.
      Bacteriological stool examination was positive in 22% in control group and 26% in
      DS group for Salmonella, Shigella, Campylobacter, enterotoxigenic Escherichia
      coli and Plesiomonas sp. Rotavirus was found in 25% of the control group and 29%
      of the DS group. Seventy-two hours after therapy, 34% of infants were cured in
      the control group compared to 71% in DS group (p < 0.01) and 5 days after the
      beginning of treatment, 34% still had diarrhea in the control group compared to
      12% in DS group (p = 0.04). The acceptability of DS was considered to be good in
      30 infants (88%). No major side effect was observed. In conclusion, DS with
      rehydration shortens the course of acute diarrhea in ambulatory infants and may
      reduce the occurrence of prolonged diarrhea. DS is well tolerated in infants with
      acute diarrhea.

PMID- 7825007
TI  - Reinfection with Schistosoma japonicum after treatment with praziquantel in
      Poyang lake region, China.
AB  - The study on reinfection with Schistosoma japonicum after treatment was carried
      out in a cohort of subjects in a heavy endemic village of Poyang lake region,
      China. After mass treatment with praziquantel in non-transmission time, detailed
      observations of water contact were estimated using the mean area of skin exposed
      daily. One year after treatment, the prevalence of infection in study subjects
      was 54.48%, returning to 83% of initial prevalence. The peak prevalence occurred
      the 11-15 year age class, but intensity of exposure also varies with age and that
      age group supporting the higher prevalence of reinfection had high levels of
      exposure. Among groups of subjects with a similar exposure stratum, young
      subjects under the age of 21 years were more heavily reinfected, while no heavy
      reinfection was observed in adults (> or = 25 years). These observations suggest
      that subjects in this area slowly acquire an increasing degree of immunity to
      lighten the intensity of infection with S. japonicum.

PMID- 7825008
TI  - Humoral and cell mediated immune responses against Schistosoma spindale in BALB/c
      mice.
AB  - (BALB/c mice were infected with cercariae of Schistosoma spindale by tail
      immersion technique and by dropping some cercariae from a pipet onto the outer
      surface of the pinna of the ears. Groups of mice were removed on Days 10, 20 and
      30 and tested for humoral and cell mediated immune responses using either adult
      worm or cercarial antigen. On Day 50 the mice were sacrificed and the worm burden
      was determined for each mouse. This method resulted in an infectivity rate of
      89.7%. There was a significant increase in antibody titer to the adult worm
      antigen while no significant increase was observed for cercarial antigen over the
      period of the study. Results obtained for cell mediated immunity were more
      dramatic. There was a significant increase in foot pad swelling for adult worm
      antigen compared to a significant decrease for cercarial antigen during the
      course of the infection.

PMID- 7825009
TI  - Partially purified antigens of Paragonimus heterotremus for serodiagnosis of
      human paragonimiasis.
AB  - The preparative crude extract of Paragonimus heterotremus was fractionated by
      isoelectric focusing. Fractions at pH 5 which contained a specific antigen with a
      relative molecular weight of 31.5 kDa were pooled and used in an indirect enzyme
      linked immunosorbent assay (ELISA) and immunoblot analysis for diagnosis of human
      paragonimiasis. The sensitivity and specificity of ELISA were found to be 100%
      and 99% respectively. The band of 31.5 kDa antigenic component was found to give
      consistent reaction with paragonimiasis sera. The sensitivity, specificity and
      predictive value (positive and negative) of immunoblot analysis for the 31.5 kDa
      band were all 100%.

PMID- 7825010
TI  - Comparative horizontal starch gel isoenzyme electrophoresis of Lymnaea
      (Bullastra) cumingiana (Pulmonata: Lymnaeidae) and related taxa in the Indo
      Pacific region.
AB  - Foot muscle tissue extracts from six lymnaeid species of the Indo-Pacific region
      [Lymnaea (Bullastra) cumingiana and L. (Radix) quadrasi from the Philippines, L.
      (R.) rubiginosa from Indonesia and Thailand, and L. (R.) viridis from Guam and
      Hong Kong] were subjected to horizontal starch gel isoenzyme electrophoresis and
      assayed for seven isoenzymes (AcP, AlP, CA, EST, LAP, CAT and GOT) to elucidate
      their taxonomic relationships. L. cumingiana exhibited banding patterns for EST,
      LAP and CAT uniquely different from the rest, thus supporting the hypothesis that
      it is a distinct species. Zymogram patterns for AlP, CA, EST and LAP attest to
      the close affinity between L. quadrasi and L. rubiginosa (Indonesia and
      Thailand). Minor differences suggest a closer relationship between the two
      geographical strains of L. rubiginosa than with L. quadrasi, lending support to
      the hypothesis that L. quadrasi is inseparable as a race or variety from the
      typical L. swinhoei Adams, which in turn is but a race of L. auricularia, which
      also encompasses L. rubiginosa. The two geographical strains of L. viridis from
      Guam and Hong Kong showed the greatest consistency with regards to similarity and
      congruence in banding patterns. Non-specific esterases (EST) were the most useful
      in distinguishing the six species from each other.

PMID- 7825011
TI  - Observations on nocturnal activity and man biting habits of malaria vectors,
      Anopheles fluviatilis, An. annularis and An. culicifacies in the hill tracts of
      Koraput District, Orissa, India.
AB  - Biting and feeding behavior of malaria vectors were studied in nine villages (5
      from Jeypore zone and 4 from Malkangiri zone) of Koraput District. Man biting
      catches comprised of 16 anopheline species including the incriminated vectors of
      this area: An. fluviatilis, An. annularis and An. culicifacies. An. fluviatilis
      was predominant and biting of this species recorded indoors throughout the year
      in both the zones. The period, during which the biting activity peaked, was
      different between the two zones and consequently the time of peak transmission
      was also different between the zones. The biting activity was at its peak between
      21.00 and 03.00 hours in both the zones. However, in cold season the biting
      activity peaked in the first quarter of the night in Jeypore zone. The
      anthropophilic index (AI) of An. fluviatilis was 26.2% in Jeypore and 83.7% in
      Malkangiri and of An. culicifacies the AI was 0.4% in Jeypore and 7% in
      Malkangiri. Analysis of gonotrophic stages of night resting females indicated
      that in Jeypore zone, the majority of An. fluviatilis female left indoors for
      outdoor resting before the completion of gonotrophic cycle, but in Malkangiri,
      the females remained indoors till the end of the gonotrophic cycle. The presence
      of full-fed females in night resting catches in Jeypore village further suggested
      that the females do not leave the house immediately after taking blood meal but
      rest for some time.

PMID- 7825012
TI  - The malaria situation on the frontiers of Yunnan Province, China.

PMID- 7825013
TI  - Age composition, natural survival and population growth of Anopheles fluviatilis
      James, 1902, the major malaria vector in the endemic belt of Koraput District,
      Orissa, India.
AB  - The population growth of Anopheles fluviatilis, the major malaria vector, was
      studied in the hill tracts of Koraput district. Immature duration ranged from 11
      to 14 days (mean = 12.42 +/- 0.99) in rainy and 12 to 17 days (mean = 14.78 +/-
      1.64) in cold season. The probability of immature survival through different
      developmental stages was maximal in ponds. Daily survival rate of adults
      fluctuated between 0.55 and 0.92. The net reproductive rate (Ro) was estimated to
      be 3.0200 for cold and 0.6486 for rainy season. The mean generation time (T) was
      slightly longer in cold season (22.32 days) than rainy season (21.24 days). The
      intrinsic rate of population increase (rm) and consequently the finite rate of
      increase (lambda) were estimated for cold and rainy seasons. Population growth
      based on adult resting density was also assessed for different seasons.

PMID- 7825014
TI  - Parasitic diseases in China.

PMID- 7825015
TI  - Utility of the force of infection model for assessing changes in the dynamics of
      bancroftian filarial infections.
AB  - Force of infection is measured in terms of the number of effective contacts that
      have been introduced into the population by infective vectors. The utility of
      such a measure in describing the dynamics of bancroftian filarial infection was
      tested. Force of infection (beta) incorporating the durations of patent period
      and pre-patent period was estimated for different age classes (assuming that it
      is constant in that particular age class) and it was found that the predicted
      post-control prevalences were close to the observed figures. Utility of Remme's
      model in areas with different transmission levels is discussed. It was examined
      whether the empirical function generally used in helminth infections to describe
      the functional relationship between beta and age could be used for lymphatic
      filariasis. The relationship between the two was not adequately described by the
      function. Force of infection, when compared with rate of acquisition calculated
      using longitudinal data, showed that this measure could be used as a crude
      estimate of rate of acquisition in places which do not have longitudinal data
      sets.

PMID- 7825016
TI  - A study of two cholera epidemics in the district of Tawau, Sabah (1989-1991).

PMID- 7825017
TI  - Isolation of Blastocystis hominis from sewage.

PMID- 7825018
TI  - Free-living ciliates in CSF of a patient with meningoencephalitis: a contaminant?

PMID- 7825019
TI  - Vibrio vulnificus septicemia in a patient with liver cirrhosis.

PMID- 7825020
TI  - Combined factor V and factor VIII deficiency with congenital heart
      disease:response to plasma and DDAVP infusion.

PMID- 7825021
TI  - Cyclospora sp causing diarrhea in man.

PMID- 7825022
TI  - Partial purification and characterization of DNA topoisomerase II from Plasmodium
      falciparum.
AB  - DNA topoisomerase II from Plasmodium falciparum was partially purified by FPLC
      using three columns: Econo-Pac Q, heparin-agarose and Mono Q. The enzyme showed
      ATP- and Mg2 +/- dependent activities in a decatenation assay, with optimum
      concentrations of 0.5 and 10 mM, respectively. Furthermore, highest activity was
      detected in the presence of 100 mM KCI. Enzyme decatenation activity was not
      inhibited by the DNA topoisomerase I inhibitor, camptothecin, but was sensitive
      to both prokaryotic and eukaryotic DNA topoisomerase II inhibitors.

PMID- 7825023
TI  - Epidemiologic characteristics of drivers, vehicles, pedestrians and road
      environments involved in road traffic injuries in rural Thailand.
AB  - This report presents descriptive epidemiology of vehicle-related crashes that
      caused severe injuries in a defined geographical area in northern Thailand,
      conducted to determine the nature of injuries and factors that contributed to the
      crashes. In each incident, the driver and other victims were identified and
      interviewed by a trained public health worker using a standard investigation
      form. During 1991, 286 single-vehicle crashes (66.4%), 117 crashes with other
      vehicles (27.1%), and 28 crashes involving pedestrians (6.5%) occurred in the
      area. These crashes injured 581 persons (551 vehicle occupants and 30
      pedestrians), of whom 36 (6.2%) died. The vehicles involved in the crashes
      included 11 bicycles (2.3%), 371 motorcycles (78.6%), and 90 other motor vehicles
      (ie, pick-up trucks, lorries, and cars) (19.1%). Motorcycle-related crashes
      accounted for the majority of injuries and deaths. Driver risk factors for
      traffic injuries, such as alcohol consumption, lack of a valid driving licence,
      limited driving experience, and being a teenage driver, occurred more commonly
      among drivers of motorcycles than of other motor vehicles. Poor vehicle
      conditions and road environments reported in some incidents may have posed
      additional risks. Pedestrian factors, including young and old age, and alcohol
      use, may also have contributed to the occurrence of pedestrian injuries. Our
      system of data collection using an investigation form can provide relevant
      information, leading to the development of appropriate accident prevention
      programs for the community.

PMID- 7825024
TI  - Nationwide survey of human parasite in China.
AB  - A nationwide survey of human parasites in China was conducted during 1988-1992,
      with a coverage of 30 provinces/autonomous regions/municipalities (P/A/M). A
      total of 2,848 pilot sites in 726 counties were selected by random sampling, and
      1,477,742 individuals residing on were surveyed by fecal examination. The status
      of paragonimiasis, hydatid diseases, cysticercosis and trichinellosis were
      summarized through data review. The overall infection rate of intestinal
      parasites was 62.6% whereas at provincial level, the highest infection rate
      (94.7%) was recovered in Hainan, and the lowest (17.5%) in Heilong-jiang. A high
      proportion (43.3%) of polyparasitism among the infected population (882,080) was
      revealed. Altogether 56 species of parasites comprising protozoa (19), trematode
      (16), cestodes (8), nematodes (12) and thorny-headed worm (1) were discovered.
      During the survey a new species and several new records were documented. The
      number of the population infected with common intestinal parasites was estimated.
      The diversities of parasite distribution were noted in different nationalities as
      well as in varied occupations.

PMID- 7825025
TI  - Prevalence of disabling conditions in a rural northern Thai community: a survey
      conducted by village health communicators.
AB  - This report presents a survey of disabling conditions conducted by village health
      communicators (VHCs) in 1989 in a rural northern Thai community. The disabled
      were first identified by a VHC and then examined clinically and socially by a
      health care team both to confirm the clinical diagnosis and to formulate an
      appropriate treatment plan. The overall prevalence rate of disabled persons was
      6.3/1,000 population. The prevalence rate was higher for males than females and
      increased with age. Locomotor disability (48.8%) was the most commonly identified
      disabling condition, with visual disability (27.8%) the next most common.
      Communication disorders, mental retardation, and psychosis constituted the
      remaining 23.4%. Of the locomotor disabilities, the major disabling conditions
      were poliomyelitis, congenital malformations, traumatic amputations, and cerebral
      palsy. Unoperated cataract accounted for 72.0% of all cases with visual
      disabilities. While the true magnitude of the disability problem may be somewhat
      understated, the data reported in this study clearly reveal that there are many
      persons with untreated disabling conditions in rural communities, and that a
      significant number of them can benefit from medical treatment and rehabilitation.
      A survey utilizing VHCs may be helpful to identify the disabled in rural
      communities.

PMID- 7825026
TI  - Effect of birth spacing on infant survival in Thailand: two-stage logit analysis.
AB  - We formulated a two-stage causal model for infant survival and applied it to data
      drawn from the 1987 Thai Demographic and Health Survey covering the fate of 5,074
      index children. The following six variables were considered as the explanatory
      variables: maternal age, maternal education, birth order, preceding birth
      interval, survival of the preceding child, and place of residence. The analysis
      suggests that the birth interval not only directly affected the chance of infant
      survival but it played the role of the filtering factor through which other
      variables indirectly operate on infant mortality. The effect of preceding child's
      death was very strong, the odds ratios for the following infant's death and short
      birth interval both exceeding three.

PMID- 7825027
TI  - Risk factors associated with morbidity and mortality of pneumonia in Thai
      children under 5 years.
AB  - ARI is the most common cause of illness and death in children under 5 years of
      age. Pneumonia is the leading cause of death. This prospective study was part of
      an ARIC project conducted to identify risk factors associated with mortality and
      morbidity of community acquired pneumonia in Thai children younger than 5 years
      of age. Study subjects were 267 moderately severe pneumonia who were admitted to
      hospital. Fifteen percent required a ventilator and were categorized as severe
      cases. Nine patients (3.4%) died and were categorized in the fatal group. From
      univariate analysis only, risk factors of fatal pneumonia were lower body weight
      (p = 0.04), paternal age less than 35 year (OR = 6.1, p = 0.01), underlying heart
      disease (OR = 12.1, p = 0.0000) and protein energy malnutrition (OR = 7.9, p =
      0.0087). Predictors on admission to predict fatal outcome were rapid respiratory
      rate > 50/minute (OR = 4.1, p = 0.03), gallop rhythm (OR = 11, p = 0.04),
      enlarged liver (OR = 13.2, p = 0.001), and cyanosis (OR = 12, p = 0.0006).
      Significant factors associated with severe pneumonia after multiple logistic
      regression were underlying heart disease (OR = 4.04, 95% CI 1-15.4), enlarged
      liver (OR = 4.31, 95% CI 1.2-15.2) and cyanosis (OR = 5, 95% CI 0.8-28.7). This
      information should create awareness in physicians who are responsible for young
      children with pneumonia. Early recognition and intervention may prevent deaths
      and complications.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7825028
TI  - Women's involvement in a rural Bangladesh water and sanitation project.
AB  - Rural women were involved in a water and sanitation project (WSS) in which health
      impacts were compared between children in two areas: intervention and comparison
      areas. In intervention area people were provided with handpumps, latrines and
      hygiene education, whereas, in the comparison area, people did not receive these
      project inputs. In the intervention area women were directly involved in the site
      selection of handpumps and latrines, their installation, construction, and
      maintenance. Observations on women's involvement and their performances in the
      intervention area are presented. About 89% of the pumps maintained by women (n =
      30), and 86% of those maintained by project workers (n = 49) were found to be in
      good working condition. Women supervised the construction of all 754 latrines,
      fenced 58% of the projects-supported latrines (n = 268) and emptied the pits of
      65% of the 276 filled-up latrines. Socio-cultural factors were not barriers to
      women's involvement and performance. The findings have policy implications for
      effective involvement of rural women towards the development of sustainable WSS
      programs.

PMID- 7825029
TI  - Smoking habits and attitudes among secondary school teachers.
AB  - A questionnaire survey to study the smoking habits and attitudes toward smoking
      among secondary school teachers in Kelantan, Malaysia was conducted between July
      and September 1992. Questionnaires were sent to 5,112 teachers through their
      respective headmasters. Sixty-three percent (3,208 teachers; 61% males, 39%
      females) responded satisfactorily. Overall, 625 teachers (20%) were current
      smokers, 141 (4%) were occasional smokers, 317 (10%) were ex-smokers and 2,123
      (67%) had never smoked. Only six (0.8%) of the 766 regular and occasional smokers
      were females. The rates of smoking among parents and siblings of smokers were
      higher than parents and siblings of non-smokers. Seventy-four percent of the
      smoking teachers admitted to smoking in the school premises. The teachers'
      attitudes about the health effects of smoking were statistically different
      between smokers and non-smokers. However, both smoking and non-smoking teachers
      had similar views regarding methods to control the smoking habit which included
      banning cigarette sales, putting a halt to the tobacco industry and banning
      cigarette advertisements.

PMID- 7825030
TI  - Maternal and newborn thyroid hormonal profile in a non-goitrous area of Myanmar.
AB  - Serum thyroxine (T4), triiodothyronine (T3) and thyrotropin (TSH) levels of 325
      pairs of blood samples from the newborn infants and their mothers were determined
      with the aim of establishing the thyroid hormonal profile of the newborn babies
      and their mothers in a non-goitrous area of Myanmar. The mean +/- SEM cord serum
      T4, T3 and TSH levels were 117.47 +/- 1.92 nmol/l, 0.57 +/- 0.02 nmol/l and 6.41
      +/- 0.84 mu/ml respectively. The corresponding maternal levels were 146.29 +/-
      2.06 nmol/l, 2.33 +/- 0.04 nmol/l and 2.59 +/- 0.17 mu/ml maternal serum T4 and
      T3 levels were significantly higher than the corresponding cord serum values (p <
      0.0001 in both cases) and maternal TSH level was significantly lower than cord
      level (p < 0.0001). Maternal and cord T4, T3 and TSH levels of premature infants
      were not significantly different from those of mature infants. Similarly maternal
      and cord hormonal levels of male infants were not significantly different from
      those of female infants.

PMID- 7825031
TI  - Anemia among pregnant women in the Asir region, Saudi Arabia: an epidemiologic
      study.
AB  - A cross sectional study was conducted during August 1992, on a representative
      sample of 6,539 pregnant women attending 69 primary health care centers in the
      Asir region, southwestern Saudi Arabia for the assessment of their hemoglobin
      level. The overall prevalence of anemia (Hb < 11 g/dl) was found to be 31.9%. It
      was found that the prevalence was affected by age (37.3% among those who were
      less than 20 years old), parity (34.9% among those who had 7 and more
      deliveries), inter-pregnancy spacing (35.2% among those whose birth spacing was
      less than 1 year), gestational age, and education (35.1% among illiterates).
      Health education programs at primary health care level in the region should be
      revised to stress the importance of balanced diet, compliance with iron
      medication and sufficient spacing between subsequent pregnancies.

PMID- 7825032
TI  - Immunogenicity of hepatitis B vaccine in premature infants.
AB  - The immunogenicity of plasma-derived hepatitis B vaccine was studied in 39
      premature neonates, whose weights were 1,800-2,400 g and gestational ages 32-37
      weeks. All maternal antiHBc antibody were negative. Dosage of 5 micrograms of
      hepatitis B vaccine (Pasteur vaccine) was given at 0, 1, 2 and 12 months after
      birth. At the ages of 1, 2, 4, 9, 12 and 13 months, antiHBs antibody was found in
      7.7%, 20%, 69.7%, 81.4%, 77.3% and 89.5%, respectively, while the geometric mean
      titer in this seropositive group, starting at age 2 months was 37, 121, 113, 69
      and 1,016 mIU/ml. There was no severe reaction attributed to the vaccination. The
      result indicated that the vaccine was immunogenic. Although the conversion rate
      was low after primary injection, a satisfactory response developed at age 4
      months after 3 doses of vaccine.

PMID- 7825033
TI  - Isolation of HIV-1 from Filipino commercial sex workers (CSWs).
AB  - Peripheral blood mononuclear cells (PBMC) from 36 HIV-1 antibody positive
      Filipino female commercial sex workers (CSWs) were co-cultivated at a 1:1 ratio
      with phytohemagglutinin-P activated PBMC from healthy, HIV-1 antibody negative
      donors. After 3-18 (mean 7.2) days of incubation at 37 degrees C in 5% CO2, 29
      cultures showed evidence of replication of HIV-1: increasing concentrations of
      p24 antigen in the growth medium and the appearance of multinucleated giant
      cells. Although the length of incubation required for the appearance of
      cytopathogenic effect for each particular isolate was essentially the same when
      either 6 microwell plates were seeded with 3.0 x 10(6) cells/well or 24 well
      plates were seeded with 1.5 x 10(6) cells/well, the 24 well format was more
      sensitive. The ability to isolate HIV-1 from PBMC did not appear to be associated
      with the progression of disease or the presence or absence of any specific
      clinical findings. However, if the PBMC were from individuals with a concomitant
      p24 antigenemia, the incubation time required for isolation was significantly
      shorter (mean 3.8 days). The absolute CD4+ lymphocyte count was also slightly
      reduced in the culture positive, p24 antigenemic patients (range 302-813
      cells/mm3, mean 502 cells/mm3) compared to the culture positive, p24 serum
      negative cases (range 311-1,511 cells/mm3, mean 830 cells/mm3). The p24 serum
      negative cases with CD4+ counts of < 500 cells/mm3 had positive PBMC cultures by
      6 days of incubation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7825034
TI  - Community beds: the future for mental health care?

PMID- 7825035
TI  - A prospective study of daily stressors and symptomatology in schizophrenic
      patients.
AB  - There has been very little research on the ability of a measure of daily
      stressors such as the Hassles Scale to predict symptomatology in schizophrenia.
      We examined this issue in a group of 55 outpatients with a DSM-III-R diagnosis of
      schizophrenia. The patients were assessed on a monthly basis for a minimum of 12
      months. The Hassles Scale was used to assess daily stressors and the indices of
      symptomatology included the Scale for the Assessment of Positive Symptoms, the
      Scale for the Assessment of Negative Symptoms, the Beck Depression Inventory, the
      Self-Evaluation Questionnaire, and the General Health Questionnaire. Longitudinal
      data on the relationship between Hassles score and symptomatology were analyzed
      for each patient. Statistically significant correlations of symptoms with
      stressors for the previous month were found in a greater number of patients than
      would be expected by chance. There was some reduction in the number of
      significant correlations when the possible role of prior symptomatology was
      statistically controlled for.

PMID- 7825037
TI  - Acceptability, sensitivity and content validity of the VECS and VSSS in measuring
      expectations and satisfaction in psychiatric patients and their relatives.
AB  - The Verona Expectations for Care Scale (VECS) and the Verona Service Satisfaction
      Scale (VSSS) are two newly developed, multidimensional instruments that measure
      expectations and satisfaction with community-based psychiatric services (CPS) in
      patients, relatives and professionals. This paper reports on the acceptability,
      sensitivity and content validity of the VECS and VSSS in 75 patients and 76
      relatives attending the South-Verona CPS. The acceptability of the VECS and the
      VSSS to subjects was good: most items were easily understood and the vast
      majority of subjects cooperated and gave accurate evaluations. The VECS and VSSS
      proved to be sensitive to variation both between groups and across dimensions. We
      demonstrated that the VECS and VSSS questionnaires had a higher sensitivity than
      unstructured interviews in measuring service expectations and satisfaction and
      that a domain-specific measurement had a higher sensitivity than an overall one.
      The content validity of the questionnaires, according to patients' and relatives'
      views, was very good. We demonstrated that a key characteristic of the content
      validity was the questionnaire's multidimensionality, with major contributions
      from the dimensions "Professionals' Skills and Behaviour" and "Types of
      Intervention". The findings presented in this paper constitute the first complete
      study available in the literature on the psychometric properties of the
      measurement of expectations and satisfaction in a psychiatric setting. They
      indicated that it is possible to measure such subjective aspects in an
      acceptable, sensitive and valid way and that the VECS and VSSS have good
      psychometric properties. The data presented appear promising in the qualitative
      evaluation of the South-Verona CPS and the method should be of interest to those
      evaluating CPS in other settings.

PMID- 7825036
TI  - Postnatal mental illness: a transcultural perspective.
AB  - The three main conditions that are associated with childbirth are the maternity
      blues, postnatal depression and post-partum psychosis. The prevalence of the
      blues, which are mild, transient and very common disturbances of postnatal mood,
      does not appear in a major way to be related to environmental, social or cultural
      factors. Postnatal depression, which has a predominantly psychosocial etiology,
      surprisingly does not appear to vary in incidence across different cultures in
      the few studies reported that permit direct comparisons. There is also no good
      evidence for or against the theory that postnatal depression is partly the
      consequence of the customs and rituals that traditionally mark the transition to
      parenthood being stripped away in developed Western societies. However, the lack
      of relevant research and limitations of method severely restrict any conclusions
      that can be drawn. There is much firmer evidence for a consistent incidence of
      post-partum psychosis across cultural and ethnic divides; this observation,
      together with clinical data and historical evidence of an unchanging incidence
      rate during the past 150 years, points to a primarily endogenous etiology for the
      psychoses, which may be triggered by the physiology of childbirth. The
      transcultural approach to postnatal psychiatric disorders provides a unique
      opportunity not only to test hypotheses about social and cultural contributions
      to the etiology of psychotic and non-psychotic reactions to childbirth, but also
      an opportunity to study the ways in which social factors can influence the
      evolution of psychopathology. It is also possible that in some cultures the
      family and social milieu may play a major part in buffering infants from the
      adverse effects of maternal postnatal illness, but the evidence is anecdotal.
      Systematic research across cultures will lead to better recognition of maternal
      illness as well as to better prevention and management.

PMID- 7825038
TI  - Integrating psychiatry into primary care: an experimental model.
AB  - General practitioners (GPs) working in a busy primary care setting attached to a
      teaching hospital were exposed to patient-centred feedback teaching in which
      symptoms elicited by the general practitioner (GP) and an interview schedule in
      the index patient were used as a focus for instruction. Each of the seven GPs who
      completed the study had an average of 52 validated exposures spread over 3
      months. Three of them became much better at detecting psychiatric disorders, two
      showed no noticeable improvement and two showed some deterioration. The
      personality and disposition of the GPs, rather than their years of experience,
      determined their response to the training programme. The implications of the
      findings is highlighted.

PMID- 7825039
TI  - Admission of British Caribbeans to mental hospitals: is it a cohort effect?
AB  - Work in the 1980s has shown that the high incidence of schizophrenia in British
      Caribbean men is restricted to those born after 1950. Data from a study of
      admissions in three London health districts suggested that the greater part of
      this excess risk may be confined to those born before 1966. This suggests that
      the group of British Caribbean men experiencing a high frequency of schizophrenia
      could be a tightly delineated birth cohort. If confirmed in wider studies, this
      could have important implications for the elucidation of the causes of one type
      of schizophrenia.

PMID- 7825040
TI  - A novel approach to preemployment worker fitness evaluations in a material
      handling industry.
AB  - STUDY DESIGN: Effectiveness of a pre-employment worker fitness evaluation in a
      sample of grocery warehouse order selectors was studied retrospectively.
      Implementation of the program began in March 1990 and as of September 10, 1993,
      1100 prospective employees have been tested. OBJECTIVES: Identification of
      prospective employees with the necessary job specific physical requirements was
      conducted with a standardized test protocol based on job analysis and normative
      data. Follow-up injury rates and costs for this department were supplied by the
      company for statistical analysis. SUMMARY OF BACKGROUND DATA: To establish
      normative data for minimum standards of job performance, a control group of
      current, uninjured and experienced order selectors was evaluated in respect to
      job requirements and isokinetic variables. In the control group, 17 variables
      were identified including one each from two 5-minute repetitive lifting tasks
      with weighted crates and 15 isokinetic trunk function and lifting variables.
      Prospective employees were required to successfully complete at least 15
      variables for hire as an order selector. METHODS: The t-test for significance of
      difference between two proportions was used to compare injury rates in 1989 to
      those reported in 1990, 1991, 1992, and 1993. RESULTS: Statistically significant
      differences were found between the unimplemented comparison year of 1989 and the
      4 years post-implementation. CONCLUSIONS: Preliminary data suggests that a worker
      fitness evaluation using the above methodology may be an effective method of
      reducing injuries and subsequent costs.

PMID- 7825041
TI  - Effect of discharge recommendations on outcome.
AB  - STUDY DESIGN: The incidence of two common discharge recommendations, return to
      work unrestricted (RTWU) and restricted (RTWR) suggested that most restrictions
      were applied on the basis of patients' subjective reports of pain or therapists'
      unfounded fears that return to full duty would result in physical harm.
      OBJECTIVES: This prospective study compares the therapist's return to work
      recommendation to the patient's actual work status and analyzes the effect of
      that recommendation on outcome. METHODS: There were 1438 consecutive patients
      reviewed by structured telephone interviews during the two halves of the study:
      the control group when pain was accepted as a reason for restriction and the
      study group when it was not. SUMMARY OF BACKGROUND DATA: In the control group,
      44% of the patients were recommended to RTWU; for the study group, 81% received
      this recommendation. Compliance was 84% for the control subjects and 78% for the
      study group. RESULTS: The absolute number of patients who returned to
      unrestricted work doubled in the study group. CONCLUSIONS: The probability of a
      successful return to normal duty increased with a recommendation of RTWU (P =
      0.0001), whereas the probability of failure increased when restrictions were
      imposed (P = 0.0001).

PMID- 7825042
TI  - Factors that affect surgical rates in Iowa.
AB  - STUDY DESIGN: This study analyzed insurance claims to estimate the probability of
      medical and surgical treatments in different Iowa communities. The likelihood of
      surgical treatment was associated with patient characteristics of age and gender
      as well as hospital characteristics of size (number of beds), occupancy rate, and
      number of staff. OBJECTIVES: Our findings are being used by a study group of 25
      physicians to understand the causes of variation in surgical rates for low back
      pain. Medical education and other interventions are being implemented. SUMMARY OF
      BACKGROUND DATA: Hospitalization rates for lower back operations in the United
      States increased by more than 20% from 1978 to 1985. Consequently, several
      studies in Iowa and the US have been initiated to examine the medical
      effectiveness of these treatments. METHODS: A logistic regression model was used
      to determine the factors associated with the likelihood of having a low back
      surgery in a population of Blue Cross/Blue Shield (BCBS) subscribers in Iowa. The
      outcome, or dependent variable, of interest was a hospitalization that resulted
      in a surgical procedure on a low back pain patient. RESULTS: Surgical rates for
      the treatment of low back pain are likely to be increased if a BCBS Iowa
      subscriber is female, older than 44 years of age, or if the surgery is performed
      in a hospital with either an occupancy rate less than 62%, with fewer than 774
      staff members, fewer than 267 beds, or no residency programs.

PMID- 7825043
TI  - The role of distraction in improving the space available in the lumbar stenotic
      canal and foramen.
AB  - STUDY DESIGN: The terminal event in disc space narrowing and facet subluxation of
      the lumbar spine can produce clinical symptoms of spinal stenosis. Reversal of
      this process via distraction was performed on ten cadaveric motion segments with
      documented stenosis. METHODS: Computerized tomography and caliperic methods for
      the measurement of canal and foraminal areas were calculated in each segment
      after 5 and 10 mm of symmetrical distraction. Measurements were done in a blinded
      manner verified with orthographic software and statistical analysis. RESULTS:
      Decompression of foraminal space was statistically significant in 7 of 10
      cadaveric specimens after 5 mm of distraction and 9 of 10 specimens after 10 mm
      of distraction. Minimal yet insignificant improvement in stenotic canal area was
      evident with distraction. CONCLUSION: The presence of posterior vertebral
      osteophytes was associated uniformly with poor improvement of space available in
      both stenotic canal and foramen.

PMID- 7825044
TI  - A prospective analysis of autograft versus allograft in posterolateral lumbar
      fusion in the same patient. A minimum of 1-year follow-up in 144 patients.
AB  - STUDY DESIGN: One hundred forty four patients who underwent lumbar spine fusions
      had autografts placed on one side as a control and on the opposite side one of
      the following types of graft material was placed: iliac autograft, demineralized
      cancellous chips, demineralized cortical powder, demineralized cortical powder
      mixed with autograft, or mineralized cancellous chips. Alar anteroposterior and
      lateral postoperative radiographs were reviewed by three independent observers
      and graded for quality of fusion mass bilaterally. The follow-up was 14 to 27
      months. OBJECTIVES: This study evaluated the efficacy of various types of
      ethylene oxide-sterilized allograft bone used for spine fusions and compared them
      with autograft iliac bone in the same patient. SUMMARY OF BACKGROUND DATA:
      Previous studies comparing autograft with allograft showed poorer fusion rates
      with allograft with posterior fusions. Most of the previous studies included
      smaller numbers of patients. No previous studies compared ethylene oxide-treated
      allograft with autograft. RESULTS: An analysis of the radiographs at a minimum of
      1 year postoperatively revealed significantly lower values when allograft alone
      or in combination with autograft was used in comparison to autograft alone.
      CONCLUSIONS: Ethylene oxide-treated allograft is inferior to autograft and should
      not be used for posterior lumbar fusions.

PMID- 7825045
TI  - Laser disc decompression. The importance of proper patient selection.
AB  - STUDY DESIGN: The value of adherence to selection criteria for laser disc
      decompression (LDD) was evaluated. A total of 204 patients who underwent LDDs
      were identified. Follow-up information could be obtained for 164 (80.8%)
      patients. Results were compared based on the selection criteria. SUMMARY OF
      BACKGROUND DATA: Laser disc decompression is a relatively new procedure. Few
      reports concerning outcome of LDD exist; and none deal specifically with patient
      selection. OBJECTIVE: This study compared the results of LDD performed among
      patients who met appropriate selection criteria with those who did not. Also, the
      value of discography in patient selection for LDD was investigated. METHODS: Two
      independent reviewers extracted data from patient charts. From this information,
      each patient was assigned to one of three groups: 1) those who met all selection
      criteria for LDD (leg pain, positive physical examination finding such motor,
      sensory, or reflex deficits, and/or straight leg raise, contained disc herniation
      confirmed by discography); 2) those who did not meet the selection criteria (had
      a normal physical examination, the presence of stenosis, spondylolisthesis,
      extruded disc fragment, leakage of discographic dye from the outer annulus,
      multiple prior lumbar surgeries); or 3) those who could not be assigned to either
      of the first two groups for reasons such as discography not being performed or
      inadequate physical examination data recorded in the chart. At 1 year follow-up,
      each patient was sent a questionnaire assessing outcome. Successful outcome was
      defined to be no subsequent lumbar surgery, the patient felt that LDD had helped,
      and if the patient was working before symptom onset, he was able to work at the
      time of follow-up. RESULTS: Among the 41 patients who met all selection criteria,
      the success rate was 70.7% (29/41); among patients who did not meet all the
      criteria, the success rate was only 28.6% (12/42); significantly less than in the
      first group (P < 0.005). Among patients who could not be assigned definitively to
      either of the first two groups, the success rate was 55.6% (45/81). Also, the
      success rate among patients with discographic confirmation of a contained disc
      herniation was significantly greater than among those who either did not have
      discography performed or extravasation of contrast was noted (70.7% vs. 44.4%, P
      < 0.035). CONCLUSIONS: These results emphasize the importance of strict adherence
      to appropriate selection criteria to obtain satisfactory results from LDD.

PMID- 7825046
TI  - Posterior transvertebral osteotomy for adult thoracolumbar kyphosis.
AB  - STUDY DESIGN: A retrospective case study was performed on the single-stage
      posterior transvertebral closing-wedge osteotomy for treatment of adult
      thoracolumbar kyphosis. SUMMARY OF BACKGROUND DATA: Forty-one consecutive cases
      in 38 patients available for follow-up, averaging 33 months (range 4-87 months),
      are included. All patients had severe pain and/or deformity; 51% of cases had
      previous fractures, and 49% had postlaminectomy failed back syndromes with
      kyphosis. A preoperative neurologic deficit was present in 34% of the cases
      including two with cauda equina syndrome. METHODS: Patient examination and
      interviews, subjective questionnaire, chart reviews, and radiographic
      measurements were performed independently. Complications, risks, benefits,
      results, and biomechanical considerations were evaluated and discussed as
      compared with other techniques. RESULTS: All cases had solid union at follow-up;
      93% maintained correction averaging 35 degrees with three requiring revision for
      failure. Postoperatively, 19.5% of the cases had new neurologic deficits with
      five (12.2%) temporary or minor and three (7.3%) major, including one with
      unimproved paraplegia at follow-up. Eight of the 14 preoperative neurologic
      deficit cases improved postoperatively; 26 additional surgeries were performed on
      18 patients most commonly for pain (x 11) and additional trauma (x 4). The
      subjective questionnaire results indicated significant patient satisfaction, with
      76% stating they would repeat the surgery and 90% recommending it to another.
      CONCLUSION: This technically demanding high-risk procedure provides an effective
      and mechanically superior correction for acute angle thoracolumbar kyphosis in
      selected adult patients, with high subjective satisfaction.

PMID- 7825047
TI  - Prostaglandin release from lumbar disc and facet joint tissue.
AB  - OBJECTIVES: The authors measured prostaglandin (PG) and leukotriene (LT) release
      from human disc and lumbar facet joint tissues. SUMMARY OF BACKGROUND DATA: High
      levels of phospholipase A2 (PLA2) have been measured in the human disc. PLA2
      releases fatty acids from lipid membranes. These can be converted to PG and LT,
      which are potent inflammatory mediators and supposed to be involved in lumbar
      diseases. METHODS: The tissues were obtained during surgery and incubated in
      Tyrode's solution. PG and LT release was measured radioimmunologically from the
      supernatant. RESULTS: Disc (4 ng/g wet weight), cartilage (21 ng/g wet weight),
      and bone (14 ng/g wet weight) released PGs but no LTs. CONCLUSION: Because PG
      release from sequestrated disc is rather low, the inflammatory effect might be
      more because of immunologic reactions.

PMID- 7825048
TI  - The influence of anulotomy selection on disc competence. A radiographic,
      biomechanical, and histologic analysis.
AB  - STUDY DESIGN: This study analyzed the radiographic, biomechanical, and histologic
      attributes of three commonly used anulotomy techniques. OBJECTIVES: This study
      defined the propensity of the anulus fibrosus to heal after discectomy and
      correlated biomechanical differences between subgroups of the motion segments
      studied. SUMMARY OF BACKGROUND DATA: No previous report that compares the
      influence of anulotomy selection on disc competence exists. METHODS: Anulotomies
      were performed on the anterolateral aspects of the lumbar discs of 54 adult
      goats. The goats were randomly assigned to one of three subgroups containing 18
      animals. In subgroup A, a full-thickness anular window was excised. In subgroup
      B, a full-thickness cruciate anulotomy was accomplished. In subgroup C, a full
      thickness anulotomy was developed by inserting a trocar, 2.5 mm in diameter, into
      the disc. RESULTS: Histologic analysis revealed that primary anular healing did
      not occur in any specimen. The anulotomy tracts in subgroup C (trocar) were
      consistently narrower than those of subgroups A and B. Discography demonstrated
      the presence of severe and early disc degeneration with subgroup A (anular
      window), a finding not observed within the trocar anulotomy group. Biomechanical
      testing demonstrated increased resistance to pull out by the trocar anulotomy
      group at 4 weeks, as well as increased torsional stiffness of the motion segment
      when compared to both window and cruciate anulotomy. CONCLUSIONS: The authors
      conclude that attempts should be made to minimize injury to the anulus fibrosus
      during the performance of discectomy.

PMID- 7825049
TI  - Morphometry of the normal cadaveric cervical spinal cord.
AB  - STUDY DESIGN: The authors measured the transverse area and diameters of the
      cadaveric cervical spinal without evidence of nervous system pathology and also
      investigated factors related to spinal cord size. OBJECTIVES: This study
      attempted to provide basic data that affords an accurate morphometric analysis of
      the human cervical spinal cord. SUMMARY OF BACKGROUND DATA: Several postmortem
      morphometric studies of the spinal cord have been performed, but the measurements
      are different among the reports, and no authorized standard has been established.
      METHODS: The authors measured the transverse area and diameters of the C7 segment
      in 152 cadaveric specimens and investigated the cord size in relation to age,
      body height, body weight, and brain weight. Of these, 14 cases were selected and
      their segments from C2 to T1 were measured. RESULTS: There was a considerable
      individual variation in spinal cord size. The transverse area of the C7 segment
      varied from 33.3 mm2 to 74.0 mm2 (mean 49.6 +/- 7.4 mm2). The cord size showed a
      strong correlation with brain weight, and to a lesser degree with age and body
      height. Although the size of the spinal cord varied from case to case, the
      relative ratio of the transverse area of each segment to that of the C3 segment
      was almost the same among the cases examined. CONCLUSIONS: This large variation
      in cord size should be taken under consideration in morphometric analyses of the
      spinal cord. When the pathologic cord conditions such as compression or atrophy
      exist, the normally expected transverse area of the affected segment in each
      individual is calculable from measurement of a given single normal segment.

PMID- 7825050
TI  - Morphometric evaluation of the cervico-thoracic junction. Practical
      considerations for posterior fixation of the spine.
AB  - STUDY DESIGN: Linear and angular measurements were performed on 128 vertebrae (16
      spines) from C5 to T5. OBJECTIVES: Vertebrae were studied to characterize
      vertebral shape and size changes in the cervico-thoracic region. SUMMARY OF
      BACKGROUND DATA: Analysis of vertebral anatomy has been extensive and well
      characterized. Regions of transitional anatomy necessitate further study due to
      the often abrupt changes in anatomic relationships. METHODS: Two observers
      performed linear and angular measurements including pedicle width, height, and
      length, as well as pedicle-body, pedicle-lamina, lamina-transverse process, and
      pedicle-lamina angular measurements. Pedicle axis projection on the posterior
      aspect of the lamina was also calculated. RESULTS: The mean pedicle width ranged
      from 7.8 mm (T1) to 4.4 mm (T5). The body-pedicle angle decreased > 4 degrees per
      level in the transverse plane, from 50 degrees (C5) to 11 degrees (T5). The axial
      projection of the pedicle changed throughout the region (compared with level
      above) and was significant for T1. CONCLUSIONS: Because of the complexities of
      the cervico-thoracic junction, additional characterization increases the
      knowledge of the anatomic relationships in this region.

PMID- 7825051
TI  - Gadolinium-enhancement characteristics of magnetic resonance imaging in
      distinguishing herniated intervertebral disc versus scar in dogs.
AB  - STUDY DESIGN: This study is an experimental investigation on the gadolinium
      contrast magnetic resonance imaging (MRI) in distinguishing sequestered disc
      fragment versus scar in dogs. The conspicousness of the disc fragment and signal
      intensities of the disc fragment and laminectomy scar were evaluated using
      gadolinium-enhanced MRI and histology. OBJECTIVES: This study investigated the
      effects of timing of gadolinium injections, gadolinium doses, and aging of scar
      or disc on the enhancement characteristics and conspicuousness of disc fragment
      in MRI. SUMMARY OF BACKGROUND DATA: Contrast-enhanced MRI has been frequently
      used as a procedure to evaluate patients with suspected recurrent herniated
      discs. In contrast-enhanced MRI, the postoperative scar tissue enhances to a
      greater extent than disc fragments. Previous reports suggest different contrast
      enhancement characteristics of scar depending on doses, timing of gadolinium, or
      maturity of scar. There are different compounds of gadolinium agents and
      different doses are becoming available. There is no previous report on the
      evaluation of gadolinium enhancement characteristics in dogs with concurrent
      herniated disc and scar. METHODS: Six conditioned Beagle dogs underwent
      hemilaminectomies and discectomies at the L3-L4 level. An autogenous disc
      fragment was obtained from the intervertebral disc of the tail. This disc
      fragment was placed anterolateral to the thecal sac, simulating a sequestered
      disc herniation. Three control animals underwent hemilaminectomies and
      discectomies alone. Each dog underwent MRI on a 1.5 Tesla scanner (3.0 mm slice
      in sagittal and axial projections with TR 500, TE 30 msec and high dose 0.3
      mmol/kg of gadoteridol). Images were obtained at 15 days, 30 days, 60 days, and
      90 days after surgery. At each imaging session, contrast enhancement was measured
      at 2 minutes, 25 minutes, and 45 minutes after gadolinium injection for kinematic
      analysis. Two animals at a time were killed on 30 days, 60 days, and 90 days
      postoperatively. Magnetic resonance imaging was done with conventional low dose
      0.1 mmol/kg of gadopentetate at 15 days and before death. RESULTS: Results
      revealed that the difference of enhancement between disc and the scar and
      therefore conspicuousness of disc fragment was greater on 2-23-minute images as
      compared with 45- minute images, and the distinction decreased with aging of the
      scar. The high dose contrast-enhanced MRI increased signal intensities for both
      disc and scar. Conspicuousness of disc fragment seemed to be better with the high
      dose gadolinium compound. CONCLUSIONS: In conclusion, contrast enhancement
      characteristics in MRI may depend on the timing of MRI after gadolinium
      injection, doses of gadolinium, and aging of scar or disc.

PMID- 7825052
TI  - Effect of lordosis on the position of the nucleus pulposus in supine subjects. A
      study using magnetic resonance imaging.
AB  - STUDY DESIGN: Healthy young women (N = 20) underwent magnetic resonance imaging
      while supine with their hips and knees flexed (flexed position) and supine with a
      lumbar roll under the low back (extended position). The posterior and anterior
      margins of the nucleus pulposus (NP) relative to posterior and anterior margins
      of the adjacent vertebral bodies were calculated from mid-sagittal T2-weighted
      images to determine the position change of the NP as a function of two supine
      postures. OBJECTIVES: This study describes the effect of two commonly used supine
      postures on the position of the NP. SUMMARY OF BACKGROUND DATA: Management of
      patients with low back pain is often based on theorized positional changes of the
      NP during spinal extension and flexion. Data describing NP positional changes
      have not been reported for noninvasive measurements. RESULTS: The distance of the
      posterior margin of the NP to the posterior margins of the adjacent vertebral
      bodies was greater in the extended compared with the flexed position. There was
      no difference in the anterior distance. Eight of the 20 subjects had at least one
      degenerative disc in the lower lumbar spine. The NPs of the degenerative discs
      did not move the same as normal discs. CONCLUSIONS: The use of a lumbar roll
      under the low back when supine causes an increase in the distance from the
      posterior margin of the NP to the posterior portions of the vertebral bodies in
      normal discs of healthy young females. Degenerative discs deform differently from
      nondegenerative discs.

PMID- 7825053
TI  - Thoracic discography. A safe and reliable technique.
AB  - OBJECTIVES: To evaluate the safety and reliability of discography used to
      investigate thoracic disc degeneration observed on magnetic resonance (MR)
      imaging studies in patients with clinical pain, we analyzed retrospectively the
      results of thoracic discograms performed on 100 outpatients. METHODS: After MR
      imaging, clinically suspect, morphologically abnormal thoracic discs and at least
      one, nearby, control level were injected with either nonionic contrast or saline,
      filmed, and individually described by the patient as concordant versus
      nonconcordant relative to clinical pain and rated in intensity on a scale of 0
      10. RESULTS: There were no serious complications in the series, and the authors
      resolved whether the injected discs related to pain in each case. They found
      discs with anular tears, intrinsic degeneration, and/or associated vertebral body
      endplate infractions to be painful approximately 75% of the time. Clinical
      concordance was approximately 50%. Control levels were usually painless.
      CONCLUSIONS: They conclude that thoracic discography can be performed safely by
      experienced individuals as a reliable tertiary diagnostic procedure to determine
      if degenerated discs on MR studies are related to clinical complaints.

PMID- 7825054
TI  - Risk factors in Klippel-Feil syndrome.
AB  - STUDY DESIGN: This study kinematically evaluated radiographs of the cervical
      spine of patients with the Klippel-Feil syndrome in flexion and in extension to
      determine alterations from normal motion and potential risk. OBJECTIVES: The
      results in the study group were compared with those of a control group and with
      published standards for expected motion of the cervical spine. SUMMARY OF
      BACKGROUND DATA: The body of orthopedic and neurologic literature suggests a
      significant problem with neurologic deficit in patients with Klippel-Feil
      syndrome. No previous study has evaluated the kinematics of the cervical spine
      with a control group of normal individuals and published standards. METHOD:
      Lateral flexion-extension radiographs of the cervical spine of 111 patients with
      Klippel-Feil syndrome were kinematically evaluated to determine the motion of
      each open interspace and to compare motion with that of a control group and
      published standards. RESULTS: A statistically significant difference of increased
      motion per open interspaces in the upper cervical segment was noted in
      individuals with Klippel-Feil syndrome when compared with the control population.
      Conversely, total motion of the lower cervical segment was significantly
      decreased in the Klippel-Feil population when compared with normal controls.
      Lower segment motion per open interspace was not significantly different when the
      two groups were compared. CONCLUSION: The results of this study suggest that
      individuals with Klippel-Feil syndrome with hypermobility of the upper cervical
      segment are at risk for neurologic sequelae, whereas those with alteration in
      motion of the lower cervical segment are predisposed to degenerative disease.

PMID- 7825055
TI  - Sacral insufficiency fractures in rheumatoid arthritis.
AB  - METHODS: All patients with rheumatoid arthritis (RA) attending an outpatient
      rheumatology clinic at a major military medical center over 6 years were included
      in follow-up for the development and subsequent course of sacral insufficiency
      fractures. RESULTS: Sacral insufficiency fractures developed in 4 of 386
      patients. Consistent with the literature, patients were female, elderly, and/or
      postmenopausal, had severe or long-standing disease, and were taking
      corticosteroids. The correct diagnosis was initially delayed because radiographs
      were normal but was later established with bone scan and sacral computerized
      tomography. Each patient improved with calcitonin and/or physical therapy over
      time. CONCLUSIONS: Patients with RA represent a unique subgroup predisposed to
      insufficiency fractures because of multiple osteoporotic risk factors. Patients
      who have RA and acute low back or buttock pain should be evaluated aggressively
      for sacral insufficiency fractures with bone and/or computed tomography scans
      regardless of normal plain radiographs.

PMID- 7825057
TI  - Lumbosacral movement in the sit-and-reach and in Cailliet's protective-hamstring
      stretch.
AB  - STUDY DESIGN: This study analyzed movement characteristics of subjects as they
      performed two different hamstring stretching activities. OBJECTIVES: The study
      determined if there were differences in lumbosacral movement as the subjects
      performed the two stretches. SUMMARY OF BACKGROUND DATA: Cailliet contends that
      his protective hamstring stretch is less apt to be stressful to the structures of
      the spine than is a more commonly done sit-and-reach stretching activity. No
      previous biomechanical investigation has tested his contention. METHODS:
      Lumbosacral movement was measured with an Ady-Hall lumbar monitor as 40
      university students (20 males, 20 females) performed a popular sit-and-reach test
      and a sit-and-reach test that subscribed to Cailliet's protective hamstring
      stretch protocol. RESULTS: Lumbosacral movement was almost identical in the two
      stretching activities. CONCLUSIONS: If lumbosacral movement is the only criterion
      to consider in evaluating the safety of these two stretching activities, it makes
      little difference which activity is chosen. If moment of inertia were the
      dependent variable rather than lumbosacral movement, possibly one activity may be
      less stressful to the structures of the spine than the other.

PMID- 7825056
TI  - Lumbar epidural varix as a cause of radiculopathy.
AB  - STUDY DESIGN: Venous outflow obstruction or congestion has been implicated in the
      etiology of some lumbar radicular syndromes. Ten cases of epidural varices or
      variants manifesting themselves as masses within the lumbar spinal canal or
      adjacent foramina have been seen. OBJECTIVES: Diagnosis was made by multiplanar
      cross-sectional magnetic resonance and computed tomography imaging and confirmed
      in five patients by operative findings. These venous abnormalities differ from
      cases of arteriovenous malformations described in the literature. METHOD:
      Surgical treatment consisting of coagulative oblation and/or excision of the
      lesion was consistently successful in the five patients who underwent operations
      for recalcitrant symptoms. The other five patients experienced spontaneous
      resolution of symptoms. Three distinctly different types of these abnormalities
      have been identified. RESULTS: The described entity may account for some
      previously unexplained or spontaneously resolving cases of lumbar radiculitis.
      CONCLUSIONS: Knowledge of the existence of this condition, its possible
      etiologies, and its imaging characteristics may assist in its recognition and
      improved management of patients with it.

PMID- 7825059
TI  - Identification of multiple B-cell transcriptional repressor elements in S mu-C mu
      intron of mouse IgH chain locus.
AB  - The S mu-C mu intron of the IgH chain locus is conserved in rodents, but its
      biological function is unknown. It has been shown that switch recombination
      breakpoints are concentrated within the repetitive sequences in the S mu region
      in mitogen-activated normal B cells. In Ig-secreting hybridomas these breakpoints
      occur most frequently at the most 5' end, and immediately upstream of the S mu
      DNA. The S mu-C mu intron appears remarkably protected from recombination.
      Because the nucleoprotein complexes that drive transcription and recombination
      may overlap, the transcriptional characteristics of this fragment were studied.
      The cis-acting regulatory elements in the S mu-C mu intron were identified by
      ligating the entire intron, or a series of subfragments to the TK promoter and
      bacterial chloramphenicol acetyltransferase gene. Expression of these constructs
      was tested in activated B cells and the nonlymphoid cell lines HeLa and HepG2.
      The complete S mu-C mu intron (1 kb) had a negative effect on TK promoter
      activity in activated B cells only when placed upstream of the promoter, in both
      orientations. Segmentation of the S mu-C mu intron has revealed that this region
      contains multiple negative elements active in B cells. A subfragment located at
      the 3' end of the S mu-C mu intron contains a B-cell-specific negative element,
      while the subfragment located at the 5'end has cell-type-independent repressing
      activity.

PMID- 7825058
TI  - Oxygen-resistant multipotent embryonic carcinoma cell lines exhibit antimutator
      phenotypes.
AB  - Stable, oxygen-resistant cell lines (O2R) were isolated from P19 and P19H22 (APRT
      hemizygote) mouse embryonic carcinoma cells by serial exposures of increasing
      durations to 95% O2. Neurally differentiated progeny were also oxygen-resistant.
      P19O2R exhibited reduced oxygen-mediated micronucleation and a 10- to 20-fold
      reduction of the forward mutation rate at the HPRT locus in 20% O2. P19H22O2R
      cells showed reduced frequencies of colonies resistant to 2,6-diaminopurine. The
      modal karyotype of P19O2R was identical to that of a nonmodal karyotype present
      in the parental line [39,X,-Y, add(14)]. There was no evidence of enhanced
      resistance to ionizing radiation. We conclude that this general approach, when
      applied to pluripotent embryonic stem cells, has the potential to lead to the
      synthesis of antimutator strains of mice.

PMID- 7825060
TI  - Adenylosuccinate synthetase: a dominant amplifiable genetic marker in mammalian
      cells.
AB  - Adenylosuccinate synthetase (AdSS) functions at the branchpoint of purine
      nucleotide metabolism leading to the synthesis of AMP. The enzyme is inhibited by
      a metabolite of alanosine, an aspartic acid analog that is highly cytotoxic for
      most cells. We show here that it is possible to use alanosine selection to
      isolate from a population of transformants those cells having the highest levels
      of AdSS activity resulting from uptake and expression of AdSS minigenes.
      Transformants isolated in this way were selected for resistance to even higher
      concentrations of alanosine and resulted in the isolation of cells with highly
      amplified copies of the transfected AdSS minigenes. We demonstrated that
      nonselectable genes can be cotransferred and coamplified with AdSS minigenes.
      These findings indicate that AdSS minigenes can be used as dominant amplifiable
      genetic markers in mammalian cells.

PMID- 7825061
TI  - Analysis of tumor suppressor gene on human chromosome 9 in mouse x human somatic
      cell hybrids.
AB  - Deletions of the short arm of human chromosome 9 (9p) are common in human
      leukemia and solid tumors. The minimum region of overlap of these deletions,
      located between the interferon genes and the methylthioadenosine phosphorylase
      gene, is partially syntenic with a region of mouse chromosome 4 that has tumor
      suppressor activity. Somatic cell hybrids between tumorigenic, MTAP-deficient,
      mouse L cells, and MTAP-competent human cells containing either a normal copy of
      9p or a 9p with a deletion involving band 9p21 were selected in culture
      conditions that require MTAP activity for continued growth. Somatic cell hybrids
      that contained a normal copy of 9p rarely formed tumors in nude mice. Cells from
      the rare tumors that grew had lost the normal 9p. Hybrid cells that contained a
      9p with deletions formed tumors more frequently, and cells from these tumors
      retained the 9p deletion chromosome. These results provide evidence that a tumor
      suppressor gene (or genes) is located on human chromosome 9 within the region of
      deletion.

PMID- 7825062
TI  - Analysis of region-specific library constructed by sequence-independent
      amplification of microdissected fragments surrounding weaver (wv) gene on mouse
      chromosome 16.
AB  - The C3-C4 region of mouse chromosome 16 was microdissected and amplified directly
      by sequence-independent amplification (SIA). The SIA product was proved to
      originate from the microdissected region by fluorescence in situ hybridization
      (FISH) and was cloned into the PCR II vector (mean insert size 506 bp). Colony
      hybridization showed that about 59% of the clones contained either unique or low
      copy number sequences. Southern blot analysis of 100 unique clones demonstrated
      that 50 clones hybridized with single (33 clones) or multiple (17 clones) bands
      on blots of DNA from a hamster-mouse hybrid cell line that contains mouse
      chromosome 16, 13 clones hybridized with mouse but not with the hamster-mouse
      hybrid DNA, 19 clones contained repetitive sequences, and the remaining 18 clones
      failed to yield bands. One third of the 100 unique clones hybridized to human
      genomic DNA. Thirty-three clones were sequenced. None of them was found in
      GenBank. Our results demonstrate that this relatively simple method of
      microdissection and cloning can produce a library of good quality.

PMID- 7825063
TI  - Spontaneous mutations at aprt locus in a mammalian cell line defective in
      mismatch recognition.
AB  - Clone B is a CHO cell line that shows a moderate mutator phenotype as a
      consequence of a defect in mismatch recognition. To identify the classes of
      mutation that accumulate spontaneously in a functional gene, we isolated and
      sequenced 54 clone B spontaneous mutants at the adenine phosphoribosyltransferase
      gene. This spectrum was compared to 42 mutants collected in the parental cells.
      Rates of AT-->TA transversions and frameshifts were strikingly increased in clone
      B (almost eight- and sixfold, respectively). Minor increases were also observed
      for GC-->TA transversions and GC-->AT transition rates. Frameshifts occurred in
      repeated sequences, and a large proportion were losses of 2 bases occurring in
      dinucleotide runs of a type similar to microsatellite sequences. AT-->TA
      transversions clustered in regions of secondary structure and their formation
      might be explained by slippage-mediated mechanisms. These data indicate that an
      important function of mismatch recognition is in repair of extrahelical bases
      generated by misalignment during DNA replication.

PMID- 7825064
TI  - Non-P-glycoprotein-mediated multidrug-resistant human KB cells selected in medium
      containing adriamycin, cepharanthine, and mezerein.
AB  - Human epidermoid KB cell lines resistant to high levels of adriamycin, C-A90, C
      A120, C-A500, and C-A1000, were isolated in selection medium containing
      increasing concentrations of adriamycin, 1 microgram/ml of cepharanthine, a
      multidrug-resistance (MDR) reversing agent, and 100 nM of mezerein, a protein
      kinase C activating agent. One of the adriamycin-resistant KB cell lines, C-A500,
      was cross-resistant to drugs that typify the classical multidrug resistance
      phenotype, such as vincristine, actinomycin D, VP-16, and colchicine. The
      accumulation of adriamycin and vincristine was decreased in C-A500 cells and the
      efflux of adriamycin from C-A500 was enhanced compared with parental KB-3-1
      cells. These adriamycin-resistant KB cells did not contain detectable levels of P
      glycoprotein or overexpress MDR1. Multidrug-resistance-associated protein (MRP)
      and MRP mRNA were expressed in the adriamycin-resistant KB cells, C-A120, C-A500,
      and C-A1000, but not in parental KB-3-1 and revertant C-AR cells. The MRP gene
      was amplified in all the MDR cells that overexpressed MRP mRNA. DNA topoisomerase
      II levels were markedly decreased in C-A500 and C-A1000 cells but only slightly
      decreased in C-A120 cells. These results indicate that MRP overexpressed in the
      resistant cells may be responsible for the reduced accumulation of adriamycin and
      vincristine and that both the increased expression of MRP and decreased levels of
      topoisomerase II underlie the drug resistance in C-A120, C-A500, and C-A1000 cell
      lines.

PMID- 7825065
TI  - On the role of lipids in cell regulatory economy.
AB  - Prenylated proteins, which contain a lipid tail, may function to enhance the self
      assembly of complementary molecular structures by providing a monomolecular film
      between the two combining regions so that electrostatic forces of attraction are
      greatly increased over that which would be established with water molecules in
      the intervening spaces. Such interactions may be important in DNA regulation, RNA
      processing, and a variety of protein-protein interactions.

PMID- 7825066
TI  - Characterization of chimpanzee-hamster hybrids by chromosome painting.
AB  - A panel of chimpanzee-human somatic cell hybrids was characterized by dual Alu
      PCR of the chimpanzee DNA in the hybrid and subsequent hybridization of the
      labeled PCR products to human and chimpanzee chromosomes. In addition to the
      identification of the intact chimpanzee chromosomes retained in each hybrid,
      chromosome fragments were identified that will be useful in regional mapping.
      This technique also revealed the presence of centric inversions.

PMID- 7825067
TI  - Cloning and comparative mapping of recently evolved human chromosome 22-specific
      alpha satellite DNA.
AB  - We have isolated and characterized a new alphoid probe, named p190.22. Its
      chromosomal location was investigated using fluorescence in situ hybridization.
      Under high stringency conditions p190.22 recognizes specifically the centromere
      of chromosome 22. A chromosome 22-specific alphoid subset has been previously
      reported in the literature (p22/1:2.1). The partial sequence and the genomic
      organization comparison strongly suggests that they recognize distinct subsets
      both specific for chromosome 22. The comparative mapping of probes p190.22 and
      p22/1:2.1 on chimpanzee (PTR and PPA) and gorilla (GGO) chromosomes was
      investigated. The two probes showed different hybridization results. p190.22, in
      particular, did not show any hybridization signal in these three species,
      suggesting a recent evolution.

PMID- 7825069
TI  - [Current status of coronary diagnosis by magnetic resonance tomography].

PMID- 7825068
TI  - [Roentgen diagnosis of renal osteopathy of the hand bones. Soft ray immersion
      radiography contra standard technique].

PMID- 7825070
TI  - [Differential MRI diagnosis in suspected spondylitis].

PMID- 7825071
TI  - [Initial results of three-dimensional planned irradiation of prostate carcinoma.
      Irradiation technique and toxicity].

PMID- 7825072
TI  - [Radiologic diagnosis of congenital choledochal cyst].

PMID- 7825073
TI  - Screening for large-bowel cancer.

PMID- 7825074
TI  - Maintenance of professional competence, continuing medical education and
      recertification (MPC, CME and RC)

PMID- 7825075
TI  - Lesser growth--who needs what and when?

PMID- 7825076
TI  - Allergology in South Africa.

PMID- 7825077
TI  - Anabolic steroids--a contemporary perspective.

PMID- 7825078
TI  - Abortion--some practical and ethical considerations.

PMID- 7825079
TI  - Surveillance of respiratory viruses. A 10-year laboratory-based study.
AB  - Respiratory virus isolates made at the National Institute for Virology from 1982
      to 1991 were studied. An active virus surveillance programme, 'viral watch',
      which recruits throat swab specimens from a network of monitoring centres--mainly
      in the Witwatersrand and Vereeniging area with one centre in Middelburg--that
      represent a cross-section of the population, provided 68% of the specimens and
      74% of the isolates, with an isolation rate of 25.5%. This was significantly
      higher than that of routine specimens (17.7%). Of the 966 isolates, influenza
      viruses accounted for 527 (54.7%), para-influenza for 122 (12.6%), respiratory
      syncytial virus for 34 (3.4%) and adenovirus for 106 (11.0%). Influenza viruses
      showed a definite seasonal peak between June and August whereas the other
      viruses, although they showed a winter predominance, were isolated throughout the
      year. An active virus surveillance programme is particularly valuable in
      monitoring respiratory virus epidemiology in the population.

PMID- 7825080
TI  - Rheumatic fever prophylaxis in South Africa--is bicillin 1,2 million units every
      4 weeks appropriate?
AB  - Rheumatic fever is a major health problem in South Africa. Although intramuscular
      benzathine penicillin (bicillin) 1.2 million units (MU) every 4 weeks is widely
      used for secondary prophylaxis, studies in other countries have shown a
      recurrence rate of 3-8% over 5-6 years in patients on this regimen. It has been
      recommended that serum penicillin concentrations should be maintained above 0.02
      mg/ml to prevent such recurrences. The World Health Organisation (WHO) and the
      American Heart Association have recommended since 1988 that patients in high-risk
      areas for the development of rheumatic fever should receive benzathine penicillin
      1.2 MU every 3 weeks rather than every 4. The aims of this study were, firstly,
      to determine the prevalence of serum penicillin concentrations below 0.02
      micrograms/ml in rheumatic fever patients on benzathine penicillin 1.2 MU 4
      weekly and, secondly, to study the effect of increasing the dose of 1.8 MU 4
      weekly in patients with subtherapeutic concentrations. Forty-five of 51 rheumatic
      fever patients (88%) in this study on benzathine penicillin 1.2 MU 4-weekly had
      low serum penicillin concentrations (< 0.02 micrograms/ml) at the end of the 4th
      week after the injection. Penicillin was detected in the urine of 30 of the 45
      patients (67%) with low concentrations, suggesting that such patients have tissue
      bound penicillin which might be important in preventing rheumatic fever. The 15
      patients (33%) with subtherapeutic serum penicillin concentrations and no
      detectable penicillin in the urine could be at very high risk for recurrent
      attacks of rheumatic fever. Fourteen of 29 patients (48%) given the higher dose
      of benzathine penicillin (1.8 MU 4-weekly) had subtherapeutic serum penicillin
      concentrations at the end of the 4th week after the injection, but in all 29
      penicillin was detected in the urine. Review of our present policy of secondary
      prophylaxis for rheumatic fever is necessary. Concentrated preparations of
      benzathine penicillin (600,000 U/ml) are not available in South Africa;
      administration of a higher dose (1.8 MU) 4-weekly would therefore require a
      double injection, which could affect compliance adversely. We recommend that
      rheumatic fever patients in our area should receive benzathine penicillin 1.2 MU
      3-weekly as recommended by the WHO until strategies for secondary prophylaxis
      have been evaluated further.

PMID- 7825081
TI  - Is ward evacuation for uncomplicated incomplete abortion under systemic analgesia
      safe and effective? A randomised clinical trial.
AB  - OBJECTIVE: To compare evacuation under systemic analgesia (fentanyl and
      midazolam) in a treatment room (ward group) with evacuation under general
      anaesthesia in theatre. DESIGN: A prospective randomised clinical trial. SETTING:
      A tertiary medical centre serving a black urban population. SUBJECTS: One hundred
      and forty-two patients with uncomplicated incomplete abortions. INTERVENTION:
      Randomisation into two groups, those for evacuation under systemic analgesia and
      those for evacuation under general anaesthesia. MAIN OUTCOME MEASURES: Both
      groups were compared in terms of safety, efficacy, acceptability, blood
      consumption and time delay between admission and evacuation. RESULTS:
      Significantly less blood was used in the ward group (37 units for 13 patients)
      than in the theatre group (65 units for 24 patients) (P < 0.03). Significantly
      less time was taken between admission and evacuation in the ward group (median 7
      hours 15 minutes) than in the theatre group (median 12 hours 38 minutes) (P <
      0.0003). Evacuation under fentanyl and midazolam was safe, effective and
      acceptable for the majority of patients compared with evacuation under general
      anaesthesia. CONCLUSION: Patients with uncomplicated incomplete abortions
      (uterine size equivalent to a pregnancy of 14 weeks' duration or less) can
      undergo evacuation safely and effectively under fentanyl and midazolam and have a
      significantly smaller chance of requiring a blood transfusion.

PMID- 7825082
TI  - Lymphoproliferative disorders in non-AIDS-associated Kaposi's sarcoma. The
      Johannesburg Hospital experience, 1980-1992.
AB  - The association of the non-AIDS-related, classic form of Kaposi's sarcoma (KS)
      with secondary malignancies, especially lymphoproliferative disorders, has
      frequently been noted. However, in endemic African-type KS, such an association
      has been reported only rarely. A review of 62 non-AIDS-related cases of KS
      treated and followed up at Johannesburg General Hospital between 1980 and 1992
      revealed 8 patients (13%) in whom KS was associated with malignant
      lymphoproliferative disorders. The prevalence of secondary lymphoproliferative
      disorders was not significantly different among patients with classic KS (3/15;
      20%) when compared with those who had African KS (4/47; 8%). In both forms of KS
      subtle disturbances of immunity have been described which may play a role in the
      pathogenesis of secondary lymphoproliferative disorders, although the factors
      responsible and the pathogenetic mechanisms involved in malignant lymphoid
      transformation in these patients have not been fully elucidated.

PMID- 7825083
TI  - The value of abrasive cytology in the early detection of oesophageal carcinoma. A
      pilot survey in Ciskei.
AB  - The use of abrasive cytology as a screening procedure in the diagnosis of early
      cancer of the oesophagus among asymptomatic rural Ciskeians was assessed. An
      inexpensive, locally manufactured brush biopsy capsule was used to obtain
      cytological material from 1,336 subjects. The technique gives a high yield, has a
      high predictive value and identifies a high prevalence of sufferers at the
      detectable preclinical phase of the disease.

PMID- 7825084
TI  - Renin-sodium profile and renal prostaglandins in the pathogenesis of systemic
      arterial hypertension in blacks.
AB  - Thirteen black women with systemic (essential) arterial hypertension, age-matched
      with normotensives, were examined during two protocols inducing sodium depletion
      and sodium loading respectively. Changes in plasma renin activity (PRA), urinary
      aldosterone values and prostaglandin E2 (PGE2) and F2a (PGF2a) excretion were
      simultaneously assessed. Renin profiles, obtained by the plotting of PRA against
      the urinary excretion of sodium, showed a 62% prevalence of low-renin
      hypertension, the remaining 38% of the patients having normal-renin hypertension.
      At basal level the hypertensives had suppressed renal synthesis of vasodilator
      PGE2 and a non-significant increase in venopressor PGF2a. This was reflected in
      the significant 32% decrease in the PGE2/PGF2a ratio. This finding was in keeping
      with their low-renin hypertension. During sodium depletion PG excretion was
      increased in both normotensive and hypertensive groups. The opposite effect was
      found during sodium loading. The results of this study do not support a
      natriuretic role for renal PGE2, but do support the hypothesis that there is
      decreased renal vasodepressor PGE2 synthesis in black hypertensive patients.

PMID- 7825085
TI  - Duchenne and Becker muscular dystrophy prevalence in South Africa and molecular
      findings in 128 persons affected.
AB  - A genetic service for Duchenne muscular dystrophy (DMD) and Becker muscular
      dystrophy (BMD) was initiated in Cape Town in 1987. Of the 143 DMD patients
      diagnosed during the period 1987-1992, 66 had a familial pattern of inheritance
      and 77 were apparently sporadic. Twenty BMD patients were identified, of whom 12
      had other affected relatives and 8 were sporadic. Overall minimum prevalence
      rates of 1/100,000 for DMD and 1/755,000 for BMD were calculated. A markedly low
      DMD prevalence in the indigenous black population (1/250,000) contributed to the
      overall low DMD prevalence in South Africa when compared with that in the UK
      (1/40,000). By means of molecular methods, the diagnosis in 42% of the affected
      DMD males was confirmed by detection of deletions in the dystrophin gene.
      Deletions were identified in 50% of Indian, white and mixed ancestry patients. In
      contrast, only 22% of blacks had identifiable deletions. DMD appears to be
      underrepresented in the black population; the low deletion frequency in this
      group suggests that unique mutations not detectable by methods used in this study
      may be more frequent in these patients than in the other populations. The
      increased DMD frequency in Indians corroborates findings reported from the UK.

PMID- 7825086
TI  - Aspects of roaccutane prescription in South Africa.
AB  - A nationwide postmarketing surveillance study on the use and outcomes of use of
      isotretinoin has been conducted in South Africa. A representative sample of
      prescribers of the drug was identified from drug utilisation data and the overall
      doctor response rate was 90.1%. A total of 766 patients was enrolled in the
      study, of which 728 were analysable for safety and efficacy. More than half the
      patients prescribed isotretinoin were women, of whom only 48.25% were practising
      some form of contraception. The mean overall dosage prescribed was 0.64 mg/kg/day
      and the mean overall duration of therapy prescribed was 15.5 weeks. The mean dose
      and duration of therapy prescribed by dermatologists was significantly higher
      than that prescribed by general practitioners. Potentially dangerous drug
      interactions involving the concomitant use of isotretinoin with tetracyclines,
      vitamin A and oral contraceptives together with antibiotics were noted.
      Mucocutaneous drying effects were the most common adverse events and the
      incidence of these effects decreased with continuation of therapy. The known
      effectiveness of the drug was confirmed by the results of the study.

PMID- 7825087
TI  - HIV-2 and its neurological manifestations.
AB  - The human immunodeficiency virus type 2 (HIV-2) produces a similar spectrum of
      illness as HIV-1, including AIDS, and is clinically indistinguishable. There is
      evidence that it is less pathogenic, with a longer natural history. HIV-2
      infection is endemic in West Africa, especially in the former Portuguese and
      French colonies. Trade, migration, war and tourism have been important factors in
      the spread of the virus through the subregion and beyond. Diagnostic facilities
      necessary for the accurate diagnosis of neurological disease are not available in
      most of Africa and autopsy reports have been few. These constraints have
      restricted the information available on the pattern of neuropathology induced by
      HIV-2. However, it possesses neurotropic properties similar to those of HIV-1 and
      produces disease by means of direct action of the virus on the nervous system,
      and immunosuppression which allows opportunistic infections and tumours to occur.

PMID- 7825088
TI  - Tobacco excise tax and children.

PMID- 7825089
TI  - Treating tuberculosis with one combination drug.

PMID- 7825090
TI  - Exacerbation of liver disease during interferon-alpha therapy for chronic
      hepatitis C.

PMID- 7825091
TI  - Psychiatric disturbances in users of anabolic steroids.

PMID- 7825092
TI  - Environmental pollution from expired medicaments.

PMID- 7825093
TI  - Inequalities in South African health care.

PMID- 7825094
TI  - A sentinel surveillance site in the north-eastern Transvaal.

PMID- 7825095
TI  - Analgesic nitrous oxide for addictive withdrawal.

PMID- 7825096
TI  - Analgesic nitrous oxide for addictive withdrawal.

PMID- 7825097
TI  - Analgesic nitrous oxide is a very safe agent.

PMID- 7825098
TI  - Freedom and responsibility.

PMID- 7825099
TI  - Urokinase thrombolytic therapy of pulmonary embolism in neurosurgically treated
      patients.
AB  - Pulmonary embolism (PE) is a severe complication in neurosurgery. The best
      treatment of PE is thrombolytic therapy, but the presence of either intracranial
      neoplasm or recent neurosurgical procedures is considered a major
      contraindication to this therapy. We have used urokinase thrombolytic therapy in
      nine of our patients with severe PE that occurred from 7 to 34 days after a
      neurosurgical operation. All patients survived. No intracranial hemorrhage
      occurred. We also advocate thrombolytic therapy for severe PE in patients who
      were recently operated on by neurosurgical procedure.

PMID- 7825100
TI  - Cerebral edema in intracranial meningiomas: evidence for local and diffuse
      patterns and factors associated with its occurrence.
AB  - In a review of 68 meningiomas with good quality computed tomography (CT) scans,
      40% had significant CT edema, in the sense of having low absorption around tumor.
      Two distinct patterns of edema could be distinguished. One was a diffuse white
      matter process appearing to represent active transudation of water into white
      matter; this occurred in 43% of tumors with edema. The second, occurring in 57%
      of tumors with edema, was a localized peritumoral process. This distinction has
      important pathophysiologic and clinical implications. The diffuse pattern did not
      appear to reflect tumor size: it was found in 54.6% of tumors from 2 to 4 cm in
      diameter and 33% of tumors over 4 cm. It appeared more often in tumors of the
      lateral sphenoid wing or subfrontal region and was more often associated with
      atypical and syncytial histological type, (p < 0.05, two-tailed t test.). It
      occurred disproportionately often in atypical tumors and appeared to reflect some
      intrinsic property of the tumor rather than compression of surrounding
      structures.

PMID- 7825101
TI  - Primary meningioma intimately related to skull: case report and review of the
      literature.
AB  - A report is made of a primary meningioma intimately associated with the left
      sphenoid ridge and temporal bone of a 41-year-old woman. The lesion produced
      hyperostosis of the involved bones, ipsilateral proptosis, and reduced vision for
      4.5 years. The radiotherapy yielded little improvement of the exophthalmos and
      vision. Review of 125 reported meningiomas intimately related to the skull and
      presenting primarily with hyperostosis and minimal soft tissue component,
      including the current case, disclosed that all but one affected the cranium
      proper, particularly the middle ear, temporal bone, frontal bone, and parietal
      bone. The exceptional one was in the mandible. They tended to occur between the
      fifth and seventh decades of life with the peak occurrence between the fifth and
      sixth decades. The average age was 46 years for overall. The female-to-male ratio
      was 2:1. Six of 125 primary meningiomas closely associated with the skull were
      malignant and two of these spread to the lungs. The pulmonary metastasis was
      spontaneous in one case.

PMID- 7825102
TI  - Intracranial plasma cell granuloma: a report of four cases.
AB  - Inflammatory pseudotumors (IPT) are rare lesions composed of inflammatory cells
      admixed with collagen tissue. Although IPT are ubiquitous, intracranial locations
      are rare. In this study, four intracranial IPT of the plasma-cell-granuloma (PCG)
      type are reported. Four patients presented with lesions located, respectively, in
      the right cavernous sinus, the left cavernous sinus with extension to the
      tentorium cerebelli, the vermis cerebelli, and the pituitary stalk. All patients
      were operated on, but complete resection could not be achieved in cases 1 and 2.
      Follow-up was favorable in all cases, although case 1 still complained of
      headaches 2 years after operation. All cases were studied on histologic and
      immunohistochemical bases, and ultrastructural analysis was performed on two
      cases. In cases 1, 2, and 4, IPT were made up of plasma cells admixed with
      lymphocytes and rare histiocytes in a fibrous tissue-the density of which varied
      from case to case. In case 3, the mass was composed of plasma cells associated
      with numerous foamy histiocytes and polymorphonuclear cells. No light chain
      restriction could be demonstrated when immunohistochemistry was performed, and
      ultrastructural study did not disclose features reminiscent of meningioma or
      histiocytosis X. Intracranial IPT should not be confused with other diseases such
      as meningioma, lymphoproliferative disorders, or histiocytosis X. Although
      intracranial locations are much rarer than pulmonary ones, histology is identical
      in both sites and shows different patterns in its evolution. This is in agreement
      with the inflammatory origin of this lesion.

PMID- 7825103
TI  - Paraganglioma of the cauda equina with associated syringomyelia: case report.
AB  - We present an association not previously described in which the rare entity of
      paraganglioma of the cauda equina was found in association with syringomyelia of
      the cervico-thoracic cord. The patient, a 50-year-old woman presented with a long
      history of lower back pain with recent onset of sciatic pain and altered
      sensation in the right leg. Surgical resection of the tumor with intraoperative
      syringostomy of the syrinx has led to eradication of all symptoms and at 5 months
      shows no evidence of residual pathology.

PMID- 7825104
TI  - Transorbital penetrating head injury with a hunting arrow: case report.
AB  - The development of more complex and diverse hunting weapons may result in an
      increase of uncommon forms of penetrating injury to the brain. We present a case
      of nonfatal transorbital arrow injury to the brain. High velocity projectile
      injuries merit certain management adaptations from gunshot or low velocity stab
      wounds. This case highlights the necessity for anterograde removal of the arrow
      in the direction of its line of trajectory. Early assessment of the patient with
      cerebral angiography to identify surgically correctable vascular injury is
      recommended.

PMID- 7825105
TI  - Atrophy and maldevelopment of the ipsilateral cerebral hemisphere after acute
      subdural hematoma in infants.
AB  - Among nine infants aged less than 4 years with acute subdural hematoma admitted
      between 1980 and 1991, five required evacuation of a hematoma. Eight of them
      survived longer than 1 month and the remaining patient who had a hematoma removal
      died 3 days postoperatively. The four infants who required evacuation of a
      hematoma and survived longer than 1 month had prolonged hemispheric swelling
      ipsilateral to the hematoma lasting for 2 weeks postoperatively. Intracranial
      pressure was higher than 25 mm Hg during this period. Diffuse high density was
      observed in the affected hemisphere in one patient 12 days after injury, which
      was assumed to be hemorrhagic infarction. Subsequently, these four infants
      developed atrophy of the cerebral hemisphere ipsilateral to the hematoma. The
      pathophysiology of the atrophy of the cerebral hemisphere ipsilateral to the
      acute subdural hematoma is discussed.

PMID- 7825106
TI  - The neurovascular relationships and the blood supply of the oculomotor nerve: the
      microsurgical anatomy of its cisternal segment.
AB  - The 27 oculomotor nerves were examined after injection of India ink or
      methylmethacrylate into the vertebral and the internal carotid arteries. The
      ventral surface of the cisternal segment of the nerve was noted to be in close
      relationship with the superior cerebellar artery (96.3%) and its pontine (37.0%),
      mesencephalic (25.9%) and perforating branches (81.5%); the posterolateral
      pontine artery (70.4%) and its branches; the anterolateral pontine branches
      (29.6%), and the perforating branches (85.2%) of the basilar artery; the
      mesencephalic perforating arteries (11.1%) and their peduncular branches (62.9%);
      the peduncular branches of the diencephalic perforators (11.1%) and the P1
      segment (18.5%); and the accessory collicular artery (3.7%). The dorsal surface
      of the nerve was in close relationships to the P1 and P2A segments (100%) of the
      posterior cerebral artery and their peduncular branches (22.2%); the posterior
      communicating artery (100%); the collicular (100%) and the accessory collicular
      artery (33.3%), and their peduncular (51.8%) or the perforating branches (22.2%);
      the medial posterior choroidal artery (25.9%) and its branches (11.1%); and the
      mesencephalic and diencephalic perforating arteries (100%). Vascular penetration
      was noted in 51.8% of the third nerves. The most common penetrating vessel was
      the collicular artery (18.5%) and its branches (22.2%). The cisternal segment of
      the oculomotor nerve was most often supplied by the mesencephalic perforators
      (88.9%). The authors discuss the possible clinical significance of the obtained
      anatomic data.

PMID- 7825107
TI  - Intracranial neurosurgery guided by functional imaging.
AB  - Neurosurgery on eloquent cortex entails important risks of functional deficits
      complicating aggressive lesion resection. In this study, advanced biomagnetic
      functional imaging of somatosensory and motor cortex combined with surface
      rendered magnetic resonance imaging displays including vascular anatomy were used
      in conjunction with a new nonintrusive intraoperative guided instrumentation
      system to resect a tumor in eloquent cortex. Intraoperative verification of the
      accuracy of pre-operative motor localization demonstrated highly accurate results
      comparing direct stimulation and noninvasive presurgical mapping. The
      applicability of surface rendered combined functional and anatomic maps of cortex
      is directly evident on comparison of preoperative computer images and
      intraoperative pictures. This combination of new technologies has a significant
      potential for reduced risk and improved outcome in neurosurgery of eloquent
      cortex.

PMID- 7825108
TI  - Clinical experience with transcranial cerebral oximetry.
AB  - Transcranial cerebral oximetry based on the principle of near-infrared
      spectroscopy has been successfully used in a variety of neurosurgical conditions,
      primarily those associated with disturbed cerebral circulation. The non-invasive
      technique of cerebral oximetry provides valuable information about brain
      oxygenation in patients with cerebral ischemia (due to occlusion or stenosis of
      the internal carotid artery). It is also used in intraoperative monitoring of
      carotid endarterectomy and surgical procedures performed under deep hypothermia
      and circulatory arrest, during neuroendovascular procedures, and in critical care
      settings (in patients with arterial vasospasm and during the terminal period).
      This article describes our preliminary clinical experience with the use of this
      new technique and summarizes the current literature on clinical and experimental
      use of transcranial cerebral oximetry.

PMID- 7825109
TI  - The 62nd annual meeting of the American Association of Neurological Surgeons.

PMID- 7825110
TI  - Commentary for "paroxysmal bilateral dysosmia treated by resection of the
      olfactory bulbs".

PMID- 7825111
TI  - Intra ventricular craniopharyngioma.

PMID- 7825112
TI  - Cardiac malignant fibrous histiocytoma (MFH) metastasizing to the brain.

PMID- 7825113
TI  - Plasma-cell gingivitis in children and adults. A clinical and histological
      description.
AB  - Plasma-cell gingivitis (PCG) is a rare, non-symptomatic lesion found in the
      attached gingiva. In the county of Sodermanland 14 cases of PCG were identified
      during the last 13 years. Clinically, the PCG is a sharply demarcated red area
      within the attached gingiva. Abundant plasma cells are found in the connective
      tissue beneath a thin epithelium. Lesions with similar clinical appearance were
      also found in the genital mucosa of five of the patients with a PCG. An extensive
      bacterial plaque was frequently found on the gingiva and teeth in the affected
      areas. Although an improved oral or genital hygiene did not heal the lesions, an
      allergic reaction to the bacterial plaque may be the cause.

PMID- 7825114
TI  - Quality of periodontal healing. I: Review of the literature.
AB  - This summary focuses on quality of healing following periodontal surgical and non
      surgical procedures. It is based on a survey of the literature on clinical,
      radiographic and histological assessment as well as on 3 recent studies on the
      quality of periodontal healing published in this Journal.

PMID- 7825115
TI  - Quality of periodontal healing. II: Dynamics of reparative cementum formation.
AB  - The purpose of the present study was to follow the formation of mineralised
      tissue (reparative cementum) on instrumented root surfaces. Twenty-four permanent
      maxillary and mandibular laterals from six, 3-4-year-old monkeys (macaca
      fascicularis) were used in the experiment. The incisors were gently extracted and
      the periodontal membrane (PDM) and cementum on the mesial surface of the roots
      removed to a distance of 1-2 mm from both the cemento-enamel junctions and the
      apices of the roots. The teeth were subsequently replanted. Ankylosis was seen
      both after 3 and 5 wks, although to a lesser degree at 5 wks to be virtually
      absent at 10 wks. It appeared that the resorptive activity predominant at 5 wks
      had removed the ankylotic fusion. After 10 weeks, a remaining layer of
      mineralised tissue, commonly referred to as reparative cementum was seen to cover
      the denuded dentine surfaces in the present study. It appeared not to be firmly
      attached to the root surface and did not show a normal cementum-morphology in
      polarised light. It had a multi-layered appearance resembling alveolar bone
      tissue and the connective tissue fibres adjacent to the reparative mineralised
      tissue-layer were not functionally oriented but rather parallel to the root
      surface. It was concluded that the formation of this mineralised tissue
      (rearative cementum) was the result of a transient ankylosis.

PMID- 7825116
TI  - Effects of conservative treatment in patients who later will be candidates for
      TMJ surgery.
AB  - In an attempt to evaluate the effect of conservative treatment in 33 patients
      with longstanding symptoms from the joint and later subjected to
      temporomandibular joint surgery, a retrospective study was made based on careful
      case records and personal follow-up. The treatment period varied widely between
      the patients but was on average 2.5 years. The result of the conservative
      treatment in these patients was, however, very slight and limited to a minor
      increase in mouth-opening capacity. All TMJ-patients, including those with the
      diagnosis ADD and suspected ankylosis, ought to have a strict treatment and
      follow-up programme in order to reduce doctor's delay if and when surgical
      intervention should be necessary. Efforts should be focused on development of
      diagnostic methods to support the selection of patients for TMJ surgery earlier
      so as to avoid prolonged unsuccessful conservative treatment.

PMID- 7825117
TI  - How do 3 to 5-year-old children handle a lozenge? A clinical-experimental study.
AB  - The aim was to investigate how 3, 4 and 5-year-old children would handle a
      placebo lozenge in the oral cavity when given instructions on how to use it. The
      material consisted of sixty-five healthy pre-school children at three day-care
      centres in the city of Stockholm. Two lozenge sizes were tested: 400 mg (10 mm in
      diameter) and 800 mg (13.5 mm in diameter). The children were told to try to keep
      the lozenge in the mouth without sucking or biting on it until asked to spit out.
      Any tablet remains were collected and weighed after 5, 10 and 15 minutes,
      respectively. The results showed that the larger lozenge gave the longest
      dissolution time. This lozenge was also well tolerated by the children. It was
      noteworthy that 62% of the children could keep parts of the lozenge in the mouth
      for at least 10 minutes. The possible benefits of using a lozenge compared with a
      conventional tablet for preventing caries has to be further investigated.

PMID- 7825118
TI  - Ethical aspects of dental care for demented patients. Methodological
      considerations.
AB  - Management of demented patients who forcefully refuse dental treatment may cause
      ethical dilemmas and arouse feelings of frustration and anxiety in the dentist.
      The aim of this study is to develop and evaluate an appropriate method for
      analysing ethical problems in dentistry for demented patients. A taperecorded
      transcribed semistructured interview was performed with four experienced and
      competent hospital dentists. A phenomenological-hermeneutic method was used in
      the analysis of the narratives and the structured parts of the interviews
      compared with the interpretation of the narratives to focus on each interview as
      a whole. The dentists' professional task in dentistry for severely demented
      patients are both treating and caring. They have to make the treatment decision
      and also perform the treatment task. This may contribute to the results of this
      study that hospital dentists' concept in conflict situations are very vague. The
      results and tendencies of this study disclose a need for further knowledge about
      the handling of ethical conflicts in dental management of severely demented
      patients. With some modifications the narrative method and the analysis model
      used in this study are suitable in further studies.

PMID- 7825119
TI  - Age-dependent appearance of synaptic currents in rat neocortical neurons in
      culture.
AB  - Rat neocortical neurons grown in dissociated cell culture were recorded with the
      whole-cell patch-clamp technique. Spontaneous inward currents were observed in
      cells that were held at a membrane potential of -80 mV in medium containing
      tetrodotoxin and Cd2+. These currents displayed amplitudes up to 140 pA and rise
      time of 1.8 +/- 0.2 ms (mean +/- SD, n = 15). They reversed near 0 mV and showed
      no voltage-dependent frequency of occurrence. Hence, they were presumably due to
      spontaneous release of transmitter. The inward currents appeared around day 10 in
      culture and were detected up to 4 weeks. When cells of different ages were
      compared, the maximal probability of recording these inward events occurred at
      around 3 weeks in culture. The inward currents were not reduced by application of
      bicuculline methiodide which is a competitive antagonist of the GABAA receptor,
      but were blocked by the broad-spectrum glutamate receptor antagonist kynurenic
      acid. Moreover, spontaneous inward events were not affected by DL-2
      aminophosphono-valerate (NMDA receptor antagonist) but disappeared following
      application of the non-NMDA receptors antagonist 6-cyano-7-nitroquinoxaline-2,3
      dione (CNQX). Our observations indicate that the inward currents represent
      miniature synaptic events that are primarily mediated by non-NMDA excitatory
      amino acid receptor subtypes. Furthermore, our findings indicate that they
      develop over time and are not present in neurons that are grown in culture for
      less than 10 days.

PMID- 7825120
TI  - Nitric oxide inhibits 3H-glutamate transport in synaptosomes.
AB  - 3H-glutamate (GLU) uptake was measured in hippocampal synaptosomes from rat
      brain. Addition of sodium nitroprusside (SNP) (Sodium nitroferricyanide), a
      generator of nitric oxide (NO), produced a time-, temperature-, and dose
      dependent inhibition of 3H-GLU uptake. The inhibition was due to changes in both
      Kd and Vmax of GLU uptake, and it was at least partially reversible upon washing.
      Addition of reduced hemoglobin (Hb), a substance that binds NO, prevented the SNP
      induced depression of uptake. Potassium ferricyanide, a compound similar to SNP,
      did not cause a reduction in 3H-GLU uptake. Utilization of another generator of
      NO, S-nitroso-N-acetylpenicillamine (SNAP), produced similar results as did NO
      itself. Decreases in uptake were also observed in the striatum and cerebellum.
      Similar treatments did not consistently affect 3H-norepinephrine (NE) uptake,
      suggesting some selectivity in the NO effect. Thus, the observed inhibition of 3H
      GLU uptake appears to be produced by NO, and it may represent a novel type of
      transynaptic retrograde regulation of transport. If found in vivo, inhibition of
      uptake activity could also be involved in the toxic effects of NO, the
      neurotoxicity of glutamate, and other potential neuronal changes associated with
      NO such as hippocampal long-term potentiation.

PMID- 7825121
TI  - MPTP-induced oxidative stress and neurotoxicity are age-dependent: evidence from
      measures of reactive oxygen species and striatal dopamine levels.
AB  - 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes marked depletion of
      dopamine (DA) levels and reduction in the activity of tyrosine hydroxylase (TH)
      in the nigrostriatal DA pathway. In the brain, the enzyme monoamine oxidase B
      converts MPTP to 1-methyl-4-phenylpyridinium (MPP+) which enters DA terminals via
      DA uptake sites. Within the DA terminals, MPP+ blocks the mitochondrial complex I
      and causes ATP depletion. This is thought to be the main cause of MPTP-induced
      terminal degeneration. In addition, reactive oxygen species (ROS) generated after
      blockade of the complex I as well as those generated due to DA oxidation may
      participate in MPTP-induced dopaminotoxicity. The present study sought to
      determine if a single injection of a large dose of MPTP generates ROS. We also
      sought to determine if these changes as well as changes in DA levels were
      correlated and age-dependent. Toward that end, we have used C57/B6N male mice
      that were 22 days or 12 months old. These animals were injected with a single
      dose of MPTP (40 mg/kg, ip). Animals were sacrificed at various times after drug
      administration. MPTP produced no significant increase in ROS nor decreases in DA
      or HVA concentrations in the striatum of the younger mice. However, DOPAC
      concentrations were significantly decreased from 15-120 min after drug
      administration. In the older mice, MPTP caused significant increases in ROS from
      the beginning to the end of the study period. DA concentrations were decreased
      from 60 min onward. DOPAC concentrations were decreased significantly after 15
      120 min while HVA concentrations were significantly increased after 60 and 120
      min.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7825122
TI  - Acute and chronic cocaine administration differentially alters striatal opioid
      and nuclear transcription factor mRNAs.
AB  - The effects of short- and long-term cocaine exposure on the expression of the
      nuclear transcription factor genes, c-fos and zif/268, as well as the opioid
      peptides, preprodynorphin (PPD) and preproenkephalin (PPE), in various regions of
      rat brain were evaluated by injecting i.p. saline or 10, 20, or 30 mg/kg cocaine
      HCl once daily for 1 or 10 days. In situ hybridization histochemistry was
      performed using 40mer oligonucleotides coding for c-fos and zif/268, or 48mers
      coding for PPD and PPE, followed by quantitative image analysis. Behavioral
      ratings demonstrated that on day 1 cocaine-induced activity increased in a dose
      dependent manner. Statistical analysis revealed that repeated administration of
      cocaine for 10 days resulted in an augmentation of the behavioral response
      elicited by acute exposure to cocaine. Image analysis of film autoradiograms
      demonstrated that 1 h after a single injection of cocaine, the expression of c
      fos and zif/268, but not PPD or PPE in the dorsal striatum and cortex, was
      enhanced in a dose-dependent manner as compared to that in saline controls. In
      contrast, administration of 30, but not 10 or 20, mg/kg cocaine for 10 days
      increased the expression of PPD but not PPE, mRNA and downregulated that of c-fos
      and zif/268 as compared to acute cocaine. These data indicate that repeated, high
      dose cocaine administration induces an increased PPD but not PPE genomic response
      and that the expression of c-fos and zif/268 is dissociable from that of PPD.

PMID- 7825123
TI  - Ultrastructural organization of the noradrenergic innervation of the superficial
      gray layer of the hamster's superior colliculus.
AB  - Immunocytochemistry with an antibody-directed tyrosine hydroxylase (TH) was
      combined with electron microscopy and serial-section analysis to examine the
      synaptic organization of the catecholaminergic projection to the stratum griseum
      superficiale (SGS) of the hamster's superior colliculus (SC). A total of 250 TH
      immunoreactive profiles within SGS were examined. Of these, 114 (45.6%) made
      synaptic contacts; 81 (71.1%) were axodendritic, and the remainder (33, 28.9%)
      were axo-axonic. Serial-section analysis was employed to evaluate the presence or
      absence of synaptic contacts for 26 profiles. Overall, 19 (73.1%) of the profiles
      followed through serial sections exhibited synaptic contacts. Double staining of
      single sections with antibodies directed against TH and dopamine-beta-hydroxylase
      (D beta H) and examination in the light microscope indicated that virtually all
      TH-positive fibers also contained D beta H. This indicated that the fibers
      examined at the electron microscopic level were noradrenergic rather than
      dopaminergic. These results suggest that norepinephrine may have both pre- and
      postsynaptic actions in the hamster's SC and that at least some of these effects
      are mediated by conventional synapses.

PMID- 7825124
TI  - GABA-ergic interneurons of the striatum express the Shaw-like potassium channel
      Kv3.1.
AB  - In addition to numerous GABA-ergic efferent neurons, the striatum contains a
      subpopulation of fast-firing GABA-ergic interneurons characterized by the
      presence of immunoreactivity for the calcium-binding protein, parvalbumin. Double
      label in situ hybridization with digoxigenin- and radiolabelled cRNA probes was
      performed on striatal sections of adult rats to identify mRNAs expressed by
      striatal GABA-ergic interneurons. In the dorsolateral striatum, only parvalbumin
      mRNA-positive neurons expressed the mRNA encoding the potassium channel Kv3.1, a
      member of the Shaw family of potassium channels with rapid activation and
      inactivation kinetics, usually found in fast-firing neurons such as the basket
      cells of the hippocampus. Colocalization of the parvalbumin and Kv3.1 proteins
      was confirmed by double-label immunohistochemistry. Parvalbumin mRNA-positive
      neurons expressed very high levels of the mRNA encoding glutamic acid
      decarboxylase (Mr 67,000: GAD67) in the dorsolateral striatum. A smaller
      proportion of double-labelled neurons was found in the ventrolateral striatum. A
      small number of densely labelled neurons for GAD67 mRNA also expressed the mRNA
      encoding the dopamine D2 receptor, but none expressed detectable levels of the
      dopamine D1 receptor mRNA. This indicates major differences in the expression of
      dopamine receptor mRNA in a majority of GABA-ergic interneurons vs. GABA-ergic
      efferent neurons of the striatum. The results suggest that distinct molecular
      characteristics are associated with the distinct electrophysiological properties
      of striatal GABA-ergic neurons.

PMID- 7825125
TI  - Intracellularly recorded response of rat striatal neurons in vitro to fenoldopam
      and SKF 38393 following lesions of midbrain dopamine cells.
AB  - The effect of long-term (6-19 weeks) 6-hydroxydopamine-induced (6-OHDA) lesions
      of midbrain dopamine cells on dopamine D1-like agonist-induced changes in the
      excitability of rat striatal neurons was investigated in vitro using tissue
      slices and intracellular recording techniques. Fenoldopam and (+/-)-SKF 38393
      predominantly decreased excitability in control preparations including striatal
      neurons located contralateral to 6-OHDA injection sites and neurons obtained from
      rats receiving sham injections or no treatment. Fenoldopam also inhibited neurons
      ipsilateral to lesions of midbrain dopamine cells. (+/-)-SKF 38393, unlike
      fenoldopam, produced predominantly increases in the excitability of ipsilateral
      striatal neurons. Superfusion of the D1 receptor antagonist, SCH 23390, blocked
      fenoldopam-induced decreases in excitability but not the (+/-)-SKF 38393-induced
      excitation of neurons ipsilateral to the lesion. Sequential application of
      fenoldopam and quinpirole, a D2/D3 receptor agonist, produced responses to both
      drugs in a majority of neurons. The results demonstrate that inhibitory responses
      to fenoldopam are mediated by D1 receptors, while excitatory effects of (+/-)-SKF
      38393 in the striatum ipsilateral to the lesion are apparently not dependent on
      D1 receptor activation. These findings also suggest that dopamine D1 and D2/D3
      receptors are able to concurrently influence the excitability of striatal neurons
      in the dopamine deafferentated striatum. Similar regulation of striatal neurons
      in vivo may contribute to dopaminergic regulation of basal ganglia output and the
      ability of dopaminomimetic agents to ameliorate symptoms of dopaminergic
      deficiency in Parkinson's disease.

PMID- 7825126
TI  - [The 1994 Nobel Prize in physiology and medicine. Signal transduction and g
      proteins].

PMID- 7825127
TI  - [The 100-year anniversary of Norwegian fracture surgery].

PMID- 7825128
TI  - [Research ethics. In the service of research?].

PMID- 7825130
TI  - [Our Latin terminology].

PMID- 7825129
TI  - [The helpless will help].

PMID- 7825131
TI  - [Language, communication, modernism and postmodernism].

PMID- 7825132
TI  - [In the beginning was the child...Is health and course of life determinated
      already in utero and during early childhood?].
AB  - This question has been asked in many medical journals in recent years. The
      British research group, DJP Barker and co-workers, has performed a series of
      studies where the delayed effects of the early environment have been documented.
      The studies comprise ecological, individual follow-up and case control studies,
      as well as studies of trends over time. They show associations between different
      measures of children's living conditions at birth and during the first year of
      life, and the prevalence of different diseases among adults, especially ischaemic
      heart disease. The Norwegian researchers Forsdahl and Waaler have also done early
      fundamental work in this field. The Barker group interprets their findings by
      suggesting that nutrition in foetal and early life is crucial. However,
      alternative interpretations of their findings have been suggested. The most
      important objection is perhaps that socio-economic conditions at birth tend to
      persist throughout life, and that these conditions are more decisive for adult
      health than the conditions associated with foetal life and birth. Longitudinal,
      prospective studies which could provide conclusive evidence are lacking.

PMID- 7825133
TI  - [New knowledge about viral hepatitis].
AB  - Epidemics caused by a faecaloral transmitted hepatitis virus other than the
      hepatitis A virus are reported from developing countries. This type of hepatitis
      is called hepatitis E and is caused by a calicivirus termed hepatitis E virus.
      Many characteristics of this disease are similar to those of hepatitis A. The
      groups usually infected are older children and young adults in developing
      countries with poor sanitary facilities. Faecal contamination of the drinking
      water is assumed to be the main path of transmission. Large epidemics with
      thousands of icteric cases have been described. Neither hepatitis A nor hepatitis
      E develops into chronicity. In pregnant women there is an unexplained high case
      fatality rate of nearly 20%. The available diagnostic tools are based upon
      demonstration of nucleic acids in the virus genome extracted from faecal and
      blood specimens and upon immunological tests founded on synthetic peptides or
      antigens developed by means of gene technology. Hepatitis E is an important kind
      of epidemic hepatitis in the countries of the third world. Up to now the source
      of the virus remains unknown, but it has been possible to inoculate and cause
      replication of the virus in primates and even pigs. The possibility that this
      kind of hepatitis is a zoonosis has to be further documented.

PMID- 7825134
TI  - [Do physicians know if their patients are satisfied? A study in general practice
      carried out by medical students].
AB  - A doctor's ability to assess to what degree his patients are satisfied may
      indicate how well the patient and the doctor communicate. The main intention of
      this study was to evaluate the doctor's ability to register a patient's level of
      satisfaction after a consultation. 19 doctors from six medical centres in Eastern
      Norway participated. In 50% of the 216 consultations the doctors were able to
      state exactly how satisfied the patients were. In most of the cases with a
      mismatch between the doctor's and his patient's ratings the patients were more
      satisfied than the doctors realized. In some of these cases, however, the doctors
      failed to observe that the patients were dissatisfied. Male doctors were able to
      state the patients' level of satisfaction more accurately than female doctors
      were. Doctors with more experience were also more accurate in their assessments.
      The method of research used in this area can be problematic. A more reliable and
      valid questionnaire should be developed.

PMID- 7825135
TI  - [Does garlic protect against vampires? An experimental study].
AB  - Vampires are feared everywhere, but the Balkan region has been especially
      haunted. Garlic has been regarded as an effective prophylactic against vampires.
      We wanted to explore this alleged effect experimentally. Owing to the lack of
      vampires, we used leeches instead. In strictly standardized research
      surroundings, the leeches were to attach themselves to either a hand smeared with
      garlic or to a clean hand. The garlic-smeared hand was preferred in two out of
      three cases (95% confidence interval 50.4% to 80.4%). When they preferred the
      garlic the leeches used only 14.9 seconds to attach themselves, compared with
      44.9 seconds when going to the non-garlic hand (p < 0.05). The traditional belief
      that garlic has prophylactic properties is probably wrong. The reverse may in
      fact be true. This study indicates that garlic possibly attracts vampires.
      Therefore to avoid a Balkan-like development in Norway, restrictions on the use
      of garlic should be considered.

PMID- 7825136
TI  - [The epidemiological transition and the conquest of plague].
AB  - In 1971, Abdel R. Omran, the epidemiologist, launched the concepts the epidemic
      transition and the demographic transition. Assuming that the epidemic and
      demographic structures of all preindustrial societies were similar, Omran
      attached these concepts to the epidemic and demographic transitions of the
      nineteenth century. He indicated that these were the only epidemic and
      demographic transitions in history. In this paper, it is argued that this
      assertion is untenable. Historically, there have been many societal transitions
      implying concurrent and interactive epidemic and demographic transitions. Two
      major historical events have been selected for illustrative purposes. The
      emergence of the western demographic system and the advent of plague in 1347 had
      dramatic impacts on epidemic and demographic conditions. Successful combat of
      plague, first in Italy, was organized with increasing efficiency from the second
      half of the fifteenth century on the basis of miasmatic-contagionist
      epidemiological notions. The antiepidemic organizations developed in this combat
      were efficient also against most other important epidemic diseases. The rise of
      antiepidemic organizations contributed to transitional change in epidemic and
      demographic structures with substantial impact on broader societal processes of
      modernization. These transitions preceded and conditioned the transitional
      processes referred to by Omran.

PMID- 7825137
TI  - [180 years of teaching and research in pharmcology in Oslo. The 100-year
      anniversary of the department of pharmacology].
AB  - The teaching of pharmacology and toxicology for medical students started in
      Norway 180 years ago, in 1814, when the first Norwegian medical school was
      founded in Kristiania (Oslo). The first professors, however, had to teach other
      medical disciplines in addition to pharmacology: Nils Berner Sorensen taught
      pathology and therapy, Fredrik Holst and Ernst Ferdinand Lochmann taught hygiene.
      100 years ago, in 1894, Poul Edvard Poulsson was appointed professor in
      pharmacology and toxicology only. Poulsson became the founder of pharmacology in
      Norway and of the Department of Pharmacology. In particular, he became known for
      his textbook of pharmacology. The first edition appeared in 1905, and the
      textbook was later translated to several languages. The article reviews the early
      history of pharmacology in Norway, based on the biographies of the professors
      mentioned above and of their successors, Klaus Hansen and Jacob Molland. The
      Department of Pharmacology was reorganized in 1966. The most recent period is
      reviewed only briefly. The present status of the department and of pharmacology
      are emphasized.

PMID- 7825138
TI  - [Surgical treatment of femoral neck fractures. The 100-year anniversary].
AB  - Fractures of the neck of the femur, and especially operative treatment of such,
      are seldom described in the older medical literature. Sir Astley Cooper (1768
      1841) was the first surgeon to describe, in 1822, the two most common fractures
      of the upper end of the femur, medial fracture and pertrochanteric fracture.
      However, like many other surgeons of his time, he believed that such fractures
      would not heal. B. von Langenbeck (1810-1887), a German surgeon, was the first to
      propose operative treatment of a fracture of the femoral neck and actually did
      one operation, but the patient died. In 1897 and 1899, J. Nicolaysen (1831-1911),
      Professor of Surgery at the National Hospital, Oslo, published first his
      technique and then the results of closed nailing of fractures of the femoral neck
      in his material of 21 patients. He performed his first operation in July 1894,
      one hundred years ago. Fracture of the femoral neck was not as common in the
      1890s as it is today. It is now one of the most frequent kinds of fracture and
      presents a major challenge to surgical and orthopaedic departments. Professor
      Nicolaysen is recognized in the international professional literature as a
      pioneer in the operative treatment of fracture of the femoral neck. His
      publications are reviewed in this article, to mark the hundredth anniversary of
      the first systematic nailing of a fracture of the neck of the femur.

PMID- 7825139
TI  - [From the early history of cancer treatment].
AB  - Skeletal finds have shown that tumorous diseases are as old as mankind itself.
      However, the appearance of such diseases have been rather differently understood,
      explained and treated throughout the history of medicine. This paper gives a
      brief survey of the development of cancer treatment and research, in Norway and
      in the other European countries.

PMID- 7825140
TI  - [Cholera hospitals in Bergen].
AB  - As early as 1831 premises for a cholera hospital were discussed in Bergen, but no
      decision was taken. On the same day that Bergen was declared to be cholera
      infected, i.e. December 18th, 1848, a Board of Health was appointed. The Board
      immediately established the city's first cholera hospital, the Christi Krybbe
      hospital. Two additional hospitals were later established in other parts of
      Bergen. The hospitals had a total of 200 beds for a population of 24,000. Bergen
      was therefore relatively well equipped with hospital beds for cholera patients. A
      number of other plans for cholera hospitals were discussed. The Board wanted the
      county to establish a cholera hospital outside Bergen, to avoid new infection
      being introduced into the city. However, no hospital other than the three
      mentioned above was taken into use.

PMID- 7825141
TI  - [Hospital records from the cholera epidemic in Bergen 1848-1849].
AB  - During the great cholera epidemic in Bergen in 1848-49, three cholera hospitals
      were established. Records from the three hospitals have been found and studied.
      Of the 1,024 cholera patients in the city, 707 were hospitalized, and of these
      430 (60.8 per cent) died. Overall, slightly more women than men were admitted to
      hospital. The women were older than the men but the mortality was the same. The
      Christi Krybbe hospital had the oldest patients but the lowest mortality. The
      staff probably acquired more experience at Christi Krybbe, which was in action
      during the whole epidemic, and the nursing may have been better there. The
      mortality in the hospitals reached a peak during the first weeks of the epidemic
      and later decreased considerably.

PMID- 7825142
TI  - [A study of health status of school children 100 years ago].
AB  - In the years 1891 and 1892 an extensive study was carried out to determine the
      health of Norwegian school children. It was the first of its kind in the country.
      16 middle schools and secondary schools from different parts of the country
      participated. The large majority of the children were between 12 and 16 years
      old, most of them from the social middle class. The plan was to study each pupil
      three times, in December 1891, in May 1892, and in August 1892. A total of 2,457
      examinations were performed amongst 930 boys and 1,340 among 616 girls. The
      average age of menarche was 14.3 years. Height and weight were of course much
      lower than for Norwegian children today, but compared favourably with the
      situation elsewhere in Europe at that time. The symptoms and signs of disease
      recorded were headache, iron deficiency anaemia, gastrointestinal complaints
      (mostly recurrent abdominal pain), scoliosis, epistaxis, varying nervous
      complaints and a few other disorders. As a result of the study it was decided to
      appoint school physicians to every school, and to improve the physical education
      of the pupils.

PMID- 7825143
TI  - [School health services in Norway--rise and fall].
AB  - Professional interest in school hygiene and in the health of the pupils developed
      in Europe towards the middle of the 19th century. In Norway, professional
      discussion started with two lengthy debates in the Norwegian Medical Society in
      Oslo in 1866 and 1868. An important issue was the possible overburdening of the
      pupils with school work. Some private schools had their school doctor at that
      time, while public schools had to wait until 1896 or later before they got a
      school doctor. As head of the school health service in Oslo 1918-32 and professor
      of hygiene 1932-38, Carl Schiotz had a dominant influence on the school health
      service in the years between the two world wars. In many respects the work was
      successful. Eradication of poverty and other profound changes in society after
      World War II called for a modernization of the school doctors' work. However,
      stagnation and regression have taken place. Since 1 January 1984, school health
      services have been administered by the local authorities. This decentralization
      has been detrimental to the school health services in many municipalities. Some
      proposals to improve the situation are mentioned briefly.

PMID- 7825144
TI  - [Social security in the future. Some tracks from our welfare' history].
AB  - In 1994 the National Insurance Scheme in Norway celebrates its 100 years
      anniversary. The first element in the present comprehensive system was the
      Industrial Workers' Compensation Act of 1894. During the next 75 years the system
      was gradually extended, and now includes sickness benefit, old-age pension,
      disability pension, unemployment benefit and rehabilitation aid, as well as
      specific benefits for certain vocations and social conditions. The different
      chapters are summarized under the National Insurance Act ("Peoples Insurance Act"
      of 1971). There has been a general political consensus in establishing and
      further developing the insurance and welfare system, both before and after World
      War II. The principles of solidarity and equality still predominate in the
      Norwegian political culture, and the national insurance system may also be the
      most important political and economic instrument for realizing these principles
      in practice, also in the future.

PMID- 7825145
TI  - [The Tronderbonden sculpture at the Nidaros Domkirke. Who is he actually?].
AB  - The collections of Nidaros Domkirke contain a large uncrowned sculpture commonly
      called "Tronderbonden". The historical identity of "Tronderbonden" is not known.
      However, several anatomical observations, as yet not recognized, do suggest his
      identity. The position of the mouth and eyelid is skewed to the left, compatible
      with a left-sided facial paralysis. There is a defect on the left side of the
      neck, behind the ear and the mastoidal process of the temporal bone, indicative
      of a muscular injury. Such an injury might also have given rise to the facial
      paralysis. Altogether, these findings are compatible with and suggest that the
      head belongs to Erling Skakke, who ruled Norway from 1162 to 1179 AD. Erling
      suffered a blow to the neck in 1152, when he was a crusader, and after this could
      only carry his head askew.

PMID- 7825146
TI  - [Disease panorama among the " Donald Ducks"].
AB  - Disease is a rather rare phenomenon among Donald Duck, his relatives, friends and
      enemies. However, an unsystematic review of the literature shows that a number of
      symptoms, signs and injuries have been reported over the 60 years during which
      these figures have amused the world. The behavioural sciences have obviously a
      lot to learn from these publications. Persons with an exaggerated interest in
      health promotion may enjoy the success of anti-smoking campaigns; even the crooks
      have quit smoking, while sexologists are better advised to read their own
      literature.

PMID- 7825147
TI  - [The contractile heart. Cellular and subcellular aspects].
AB  - The excitation-contraction coupling can be defined as the mechanisms involved
      when the action potential initiates a contraction response of the cardiac muscle
      cell. The action potential is conducted from cell to cell, resulting in a
      synchronized contraction of the myocardium. Both the propagation of the action
      potential and the myofibrillar contraction are dependent on changes in free Ca++
      concentrations. Recently, the mediators and the molecular and structural
      components involved in the subcellular transforming of the action potential into
      a contraction have been characterized. The opening of voltage-dependent L-type
      Ca(++)-channels in the cell membrane stimulates a release of Ca++ from the
      sarcoplasmic reticulum. This Ca(++)-mediated Ca(++)-release appears to be a
      graded mechanism and is associated with the presence of structural couplings
      (Ca++ synapses) in the cardiac muscle cell.

PMID- 7825148
TI  - [Episiotomy--an appeal for a more restricted use].
AB  - Episiotomy is one of the most widely performed surgical procedures, and
      episiotomy rates of 50-90% are common. The major presumed benefit of episiotomy
      is prevention of perineal lacerations, especially rupture of the anal sphincter.
      Prevention of damage to the pelvic floor, and the relief of harmful pressure on
      head of the foetus, have also been suggested. There is very little evidence to
      support these assumptions. On the contrary, the results of three randomized
      studies suggest that high rates of episiotomy are associated with increased risk
      of sphincter rupture. These and other studies are described. In view of the long
      term morbidity of sphincter rupture, a more selective use of episiotomy is
      recommended. A rate of 20-30% seems appropriate. Indications for episiotomy are
      discussed. These should include delivery by forceps, and perhaps delivery by
      ventouse. In other cases the use of episiotomy should be restricted.

PMID- 7825149
TI  - [Malaria in Norway--a tropical disease off the track?].
AB  - Today, malaria is most often thought of as a tropical disease. Two and a half
      billion of the world's population live in malaria endemic areas, most of them in
      the tropics, and one million die of malaria annually. The explanation of the
      appearance and disappearance of malaria is multifactorial. However, increasing
      interest is being shown in the socioeconomic aspects of many diseases, and it is
      interesting to observe that diseases found in Europe as late as in the 18th and
      19th century are also predominant in today's developing countries. Research in
      medical history can make a significant contribution to the efforts to find the
      reasons for the appearance and disappearance of a disease. It is well known that
      malaria was common on the European continent, but it is less well known that
      malaria also existed in Norway during the 19th century.

PMID- 7825150
TI  - [Medical research and ethics. A questionnaire study among project leaders in the
      health region 4].
AB  - A questionnaire survey concerning attitudes to medical research ethics and the
      ethics committee was conducted among the 159 principal investigators whose
      protocols had been assessed by the regional ethics committee for biomedical
      research in the years 1986-92. Of the 119 respondents, 80% agreed that results of
      medical research can be misused and more than 60% that the public should have
      insight into and access to research results. More than half said it might be
      necessary to withhold results and that individual investigators should be able to
      do so to prevent misuse. Some 80% stated that ethical considerations had
      influenced their research, 12% that they would have had ethical scruples today
      about some of their previous projects and 60% that they currently emphasized
      ethical considerations more than they did in their earlier career. One in ten
      said they might have achieved better results if they could have paid less
      attention to ethics, while 45% would never publish studies of dubious ethical
      quality.

PMID- 7825151
TI  - [Medical research and the ethics committee. A questionnaire study among project
      leaders in the health region 4].
AB  - All 159 principal investigators whose projects had been assessed by the
      biomedical research ethics committee in Health Region 4 (Central Norway) during
      1986-92 were asked to complete a questionnaire about medical research ethics and
      the work of the ethics committee. Their answers about scientific fraud and
      misconduct have been published previously. This paper reports how the 119
      respondents (70% of those addressed) regard the role and work of the ethics
      committees and how they perceived the committee's assessment of their own
      project. A majority agreed that medical ethics committees are an important part
      of the scientific community (90%), that scientific quality is an important
      ethical element of any project (85%), and that researchers put more effort into
      their study protocol as they knew it would be assessed by an ethics committee
      (85%). More than 70% agreed that the committee's comments were useful and
      relevant, but a majority of these agreed only partly. The results are discussed
      in relation to the characteristics of the investigators.

PMID- 7825152
TI  - [Home delivery and scientific reasoning].
AB  - Doctors commonly assume that it is safer for all women to give birth in hospital
      rather than at home. Nevertheless, all statistical comparisons relevant to Nordic
      women today show that for healthy pregnant women it is at least as safe to give
      birth at home--and perhaps even safer. Furthermore, many randomised clinical
      trials consistently show that several of the elements which characterize home
      births make the births proceed much easier. The question is raised, in what ways
      it is possible to convince obstetricians that they should base their judgements
      and advice regarding place of birth on empirical evidence rather than on "well
      established" but pre-scientific dog-mas.

PMID- 7825153
TI  - [The 100-year anniversary of the surgical society in Oslo].

PMID- 7825154
TI  - [Marketing of inhalation steroids].

PMID- 7825155
TI  - [Balloon dilatation of postoperative esophageal stenoses in children].

PMID- 7825156
TI  - [Questionable guidelines on solid food to breast-fed infants].

PMID- 7825157
TI  - Intraoperative control following femorodistal revascularization: angioscopy is
      superior to angiography.
AB  - Intraoperative angioscopic control was performed in an early series of 27
      patients undergoing peripheral vascular surgery. The majority were complex or re
      do operations; reversed saphenous vein and PTFE-grafts were used as bypass
      material exclusively. Angioscopic findings were compared to conventional
      angiography with respect to the detection of technical problems leading to
      further surgical procedures. Angioscopy was feasable in 92.5%, it failed twice
      due to irrigation problems, which was before we used a dedicated angioscopy
      roller-pump. In 6 patients relevant findings requiring further surgical
      manipulations were only detected angioscopically, in 2 patients such findings
      were detected by angioscopy as well as by angiography. Such findings included
      technical problems (graft rotation [n = 1], anastomotic narrowing [n = 2]),
      balloon catheter injuries after thromboembolectomy (n = 2) and residual thrombi
      after local thrombectomy (n = 3); 5 of these patients had undergone previous
      vascular procedures in the same operation field. After local correction (n = 5)
      or placement of a new bypass (n = 3) there was no early graft failure. This early
      angioscopic experience confirmed previous reports that satisfactory visualization
      and specific recognition of angiographically unsuspected problems after
      peripheral reconstructions can be obtained by intraoperative angioscopic control.
      This was seen very distinctively in more complex and re-do operations, which we
      see as the cases most needing routine angioscopic control.

PMID- 7825158
TI  - Aorto-caval fistula--an uncommon complication of infrarenal aortic aneurysms.
AB  - Aorto-caval fistulas are an uncommon complication of infrarenal aortic aneurysms,
      being found in 0.22% to 6.04% of all cases. Operating on 1231 patients with
      abdominal aortic aneurysm in the last 30 years we saw 17 patients with an
      aortocaval fistula. While 5 patients showed an isolated fistula, 12 had an
      additional rupture of the aneurysm into the retroperitoneal space or the
      abdominal cavity. Only in four patients was the aorto-caval fistula diagnosed
      preoperatively. In 16 patients the fistula was closed from within the aorta. One
      patient needed ligation of the vena cava and the iliac veins. Mortality rate was
      40% in the group with isolated fistula and 66.7% in the group with concomitant
      rupture. Aorto-caval fistula is a severe complication of abdominal aortic
      aneurysms, which may be fatal and demands early diagnosis and prompt treatment.

PMID- 7825159
TI  - The octogenarians--a new challenge in cardiac surgery?
AB  - The per- and early postoperative outcomes of 75 consecutive octogenarians (38
      male, 37 female, mean age 81.7 years) who underwent open heart surgery were
      analysed to identify independent variables of risk factors influencing morbidity
      and mortality. There were 48 coronary bypasses. 20 valve replacements, and 7
      combined procedures. Multivariate analysis revealed that functional class (New
      York Heart Association), operative procedure, aortic cross clamp time, total
      bypass time, and age are independent predictors for morbidity and mortality (p <
      0.05). There were 6 postoperative deaths (8%). Postoperative complications
      included haemorrhage (2), stroke (1), unstable sternum (2), acute cholecystitis
      (1), pneumothorax (2), and urinary tract infection. It is concluded that
      octogenarians may benefit from open heart surgery at an acceptable risk.

PMID- 7825160
TI  - Protein C response to induction of warfarin treatment after coronary bypass
      operation.
AB  - To investigate the effect of warfarin on the anticoagulant pathway, protein C
      antigen and activity levels were compared in two groups of patients treated with
      different regimens of sodium warfarin during the initial stage of anticoagulant
      therapy following heart surgery. Group I received 6 mg of warfarin per day for 3
      days. Group II received 8 mg twice a day for 2 or 3 days. Preoperative levels of
      Protein C antigen and activity averaged 108 +/- 16% and 102 +/- 18% (mean +/-
      SD), respectively, and by one hour after the operation, levels had fallen
      significantly (protein C antigen to 76 +/- 14%; protein C activity to 70 +/-
      16%). After the initiation of warfarin treatment, the levels of protein C
      activity in group II were significantly lower than those of group I. In contrast,
      the reductions in factor X were much slower and were similar in the two groups.
      As the factor X level reflects the antithrombotic effect of warfarin, this result
      suggests that the rapid reduction of protein C activity may have given rise to a
      transient hypercoagulable state in the patients of group II.

PMID- 7825161
TI  - Omentopexy and muscle transposition: two alternative methods in the treatment of
      pleural empyema and mediastinitis.
AB  - From March 1987 to March 1993, 64 patients with chronic empyema and mediastinitis
      were treated with omentum and thoracic muscle transposition. There were 36 male
      and 28 female patients, age range 29 to 76 years. 31 patients suffered from
      chronic empyema and bronchopleural fistula after lung surgery, 18 patients had
      chronic empyema after pulmonary inflammatory disease, and 15 patients developed a
      mediastinitis with or without pleural empyema after cardiac surgery or
      irradiation of the chest wall. The pedicled omentum was used in 33, the thoracic
      muscles latissimus dorsi, pectoralis major, serratus anterior, and trapezius
      either alone or combined in 31 cases. There were no perioperative deaths.
      Bronchopleural fistulas and infected spaces were successfully closed in 61
      patients (95.3%). Postoperative CT scan, angiography, bronchoscopy, and lung
      function tests demonstrate the efficacy of both surgical methods. Omentum pedicle
      and thoracic muscle flaps supply excellent vascularised tissue to fill infected
      pleural space and mediastinum, particularly in patients with limited
      cardiopulmonary function.

PMID- 7825162
TI  - Treatment of postoperative chylothorax by pleurodesis with the streptococcal
      preparation OK-432.
AB  - Of the 2877 patients who underwent chest surgery at our department during the 20
      year period between 1973 and 1992, 9 (0.3%) developed postoperative chylothorax.
      The underlying disease included primary lung cancer in 5 patients, pulmonary
      metastasis in 1, invasive thymoma in 2, and neuroblastoma of the posterior
      mediastinum in 1. For the treatment of chylothorax, the thoracic duct was ligated
      in 2 patients with a high volume of chylous leakage. In 6 patients treated
      conservatively, early pleurodesis was attained by injecting 1 to 5 doses (mean:
      2.2 doses) of the streptoccal preparation OK-432 intrathoracically; favorable
      results were achieved. In 1 patient, the diagnosis of chylothorax was delayed
      because of postoperative pyothorax. This patient developed nutritional
      deficiency, compromised immunity, and disseminated intravascular coagulation
      (DIC), which led to death before the chylothorax could be treated. In principle,
      postoperative chylothorax should be treated conservatively. Favorable results can
      be expected with the intrathoracic injection of OK-432 beginning at the early
      postoperative period to achieve pleurodesis, combined with the prevention of
      nutritional deficiency, electrolyte imbalance, and infection.

PMID- 7825163
TI  - Coronary arteriovenous fistula: surgical correction of a rare form.
AB  - In a 60-year-old woman with long-standing angina left heart catheterisation
      revealed peripheral and central coronary arteriovenous fistulae connected to the
      left and right coronary system and opening into the pulmonary artery. The
      fistulae connected to terminal coronary artery branches were corrected by
      ligation of these feeding arteries while the electrocardiogram was continuously
      monitored. The central fistulae were closed via a transcoronary approach of the
      left anterior descending artery. Knowledge of different surgical techniques helps
      to prevent perioperative myocardial infarction and late fistula recurrence.

PMID- 7825164
TI  - Partial mitral valve replacement with a mitral homograft in subacute
      endocarditis.
AB  - In a case of subacute endocarditis, the diseased parts of the mitral valve were
      replaced by the corresponding parts of a mitral valve homograft. This technique
      was studied experimentally in animals in the sixties and seventies, but was never
      performed clinically on a large scale in humans. By preserving a functional
      papillary muscle and chordae tendinae complex, ventricular function is more
      efficient than in the case of replacement of the valve by a prosthesis. The
      absence of any prosthetic material in an infected area also decreases the
      possibility of reinfection. In performing this type of operation, surgical pit
      falls such as fistulas at the region of the annulus, dehiscence of papillary
      muscle, or rupture of the chordae tendinae have to be avoided. Surgeons have to
      be supplied with high-quality homograft valves of different sizes to obtain
      optimal hemodynamic results.

PMID- 7825165
TI  - Right-ventricular myxoma presenting as right-ventricular outflow-tract
      obstruction--case report and review of the literature.
AB  - Myxoma of the right ventricle is of very rare occurrence. An adult male patient
      presented with Class III dyspnoea and occasional haemoptysis and clinically was
      suspected to have pulmonary stenosis. Magnetic resonance imaging study revealed
      presence of myxoma arising from the right-ventricular free wall and prolapsing
      into the pulmonary artery but not involving the pulmonary valve. The myxoma was
      excised via right ventriculotomy using cardiopulmonary bypass. The patient had an
      uneventful recovery. The relevant literature is reviewed.

PMID- 7825167
TI  - The use of intra-aortic balloon pump after surgical treatment of DeBakey type I
      dissecting aneurysm of the aorta.
AB  - The case is reported of a sixty-four-year-old patient with DeBakey type I aortic
      dissection in whom postoperative extensive intra-aortic balloon pumping was
      applied. Surgical repair involved replacing the ascending aorta with a Medtronic
      Hall valved conduit. After surgery severe low-output syndrome occurred. Despite
      the use of high-dose inotropic drugs the patient could not be hemodynamically
      stabilized. An intra-aortic balloon pump was finally applied as a therapeutical
      last resort. Within three days, under counterpulsation, the patient reached a
      stable hemodynamic condition. After twenty-one days in the intensive care unit,
      he could be transferred to a normal ward. The patient was discharged on the fifty
      fourth postoperative day. During counterpulsation there were no balloon- or
      catheter-induced complications. Follow-up at five months showed the patient in
      good general health: echocardiography did not identify any lesions of the
      thoracic aorta which could be linked to counter-pulsation. It is concluded that
      the postoperative use of intra-aortic balloon pump in the event of DeBakey type I
      dissecting aneurysm of the aorta, and adversely affected patient hemodynamics, is
      a justifiable therapeutical alternative.

PMID- 7825166
TI  - Biatrial drainage of right superior vena cava with anomalous right pulmonary
      venous connection.
AB  - A case of right superior vena cava draining to both atria, predominantly to the
      left atrium, with anomalous right pulmonary venous connection to the lower right
      superior vena cava is reported. The haemodynamic significance of these anomalies
      is discussed, and the technique of surgical repair is described. The literature
      on this rare but interesting clinical entity is briefly reviewed.

PMID- 7825168
TI  - Multicentric angiofollicular lymph-node hyperplasia associated with myasthenia
      gravis.
AB  - Castleman's disease is often referred to as giant lymph-node hyperplasia.
      Although this localized disorder most commonly involves the mediastinum, recently
      many patients have been described with multicentric lymph-node hyperplasia
      associated with various clinical abnormalities. Here a new case of multicentric
      angiofollicular lymph-node hyperplasia associated with myasthenia gravis and
      gammopathy is presented. At first, the patient responded to surgery well, but
      after some months her condition deteriorated: plasmapheresis was then performed,
      one year after the operation, with great clinical improvement.

PMID- 7825170
TI  - Colonoscopic polypectomy with local injection of methylene blue.
AB  - For safer and complete colonoscopic polypectomy of large broad-based adenomas, we
      attempted submucosal injection of methylene blue before electrosurgical snare
      excision. Twenty-five large broad-based sessile adenomas 20 mm or more in
      diameter were resected. Methylene blue was injected about 2 mm away from the edge
      of the lesion. After injection, the lesion appearing as a blue bleb was resected
      by snare polypectomy. All the lesions were completely resected by single-step
      polypectomy. During and after polypectomy, no complication occurred. Endoscopic
      resection of large sessile adenomas with the aid of submucosal injection of
      methylene blue thus appears to be safe and effective.

PMID- 7825169
TI  - Orally administered beraprost sodium inhibits pulmonary hypertension induced by
      monocrotaline in rats.
AB  - Rats were fed on distilled water (DW) or DW containing beraprost sodium (BPS).
      BPS concentration was 1.5 or 3.0 mu/ml in DW for the low BPS groups and 6.0 or
      10.0 mu/ml in DW for the high BPS group. Monocrotaline (MCT) was subcutaneously
      given (60 mg/kg), and saline was injected as control. Data were analyzed among
      the following groups; Groups (Saline + DW), (Saline + Low BPS), (MCT + DW), (MCT
      + Low BPS) and (MCT + High BPS). Three weeks later, pulmonary (Ppa) and systemic
      (Psa) arterial pressure were measured under anesthesia. MCT caused significant
      elevation of Ppa [18.3 +/- 0.6 cmH2O for Group (Saline + DW) vs. 27.2 +/- 1.2
      cmH2O for Group (MCT + DW), p < 0.001, mean +/- S.E.] and Ppa was significantly
      and dose-dependently suppressed by BPS; Group (MCT + DW) vs. Groups (MCT + Low
      BPS), 23.4 +/- 0.7 cmH2O and (MCT + High BPS), 22.5 +/- 0.5 cmH2O, p < 0.05, mean
      +/- S.E.). Psa was not lowered dose-dependently by BPS. We conclude that oral
      beraprost sodium suppresses pulmonary hypertension produced by monocrotaline in
      rat.

PMID- 7825171
TI  - Increased expression of mineralocorticoid receptor in human ileum after total
      colectomy: immunohistochemical and immunoblotting studies.
AB  - Aldosterone is known to regulate transmembrane ion transport and water absorption
      through its binding to mineralocorticoid receptor (MR) in the mammalian colon. A
      possible roles of aldosterone has been suggested in increased water absorption
      from remnant ileum in the patients with total colectomy. We, therefore, studied
      immunolocalization of MR in remnant ileal mucosa in the patients with total
      colectomy in order to study the role of aldosterone in water and sodium
      absorption in these patients. Immunohistochemical localization of MR was
      performed in ileal mucosa of 7 patients with total colectomy and 5 cases of
      normal ileum obtained from the resection of ascending colon due to carcinoma by
      using a polyclonal antibody raised against a mineralocorticoid receptor fusion
      protein as a primary antibody and a biotinstreptavidin system for immunostaining.
      Immunoblotting was also performed. Positive MR immunoreactivity was observed in
      both cytoplasm and nucleus of absorptive cells of ileum of total colectomy
      patients but not in control normal ileum. Immunoblotting revealed the presence of
      an approximately 100 kDa immunoreactive product corresponding to
      mineralocorticoid receptor. Aldosterone is considered to act on ileal mucosa
      following total colectomy and the aldosterone dependent sodium transport and
      water absorption may be accelerated in ileal mucosa after total colectomy, which
      is consistent with the postoperative decrease in the stool volume observed in
      these patients. In conclusion, increased expression of the mineralocorticoid
      receptor in remnant ileum may play an important role in intestinal adaptation in
      total colectomized patients.

PMID- 7825172
TI  - Colorimetric microdetermination of l-lactate in deproteinized blood.
AB  - The method by MacQueen and Plaut was modified to devise simple microdetermination
      method of l-lactate which is applicable to deproteinized blood sample. Blood was
      deproteinized with addition of 25% (w/w) trichloroacetic acid (TCA), and 0.075 M
      2-amino-2-methyl-1, 3-propanediole (AMPD) was used to make pH of the reaction
      mixture optimal. It was validated in recovery and precision study, and showed
      good correlation with usual UV method; correlation coefficient was 0.985, and
      slope was 0.994. TCA-blood mixture may be kept at room temperature for at least 2
      hr without centrifugation, and the supernatant may be preserved for at least 2
      weeks at 4 degrees C.

PMID- 7825173
TI  - Control of diabetes during rehabilitation for diabetic stroke.
AB  - Changes of diabetic control during rehabilitation therapy was studied
      retrospectively in 33 cases of diabetic stroke. Diabetic control was not
      deteriorated in any cases during rehabilitation therapy. In 21 cases, treatment
      of diabetes was not changed during rehabilitation therapy and the levels of
      fasting plasma glucose were decreased in all of them. Doses of hypoglycemic
      agents was reduced without significant deterioration of diabetic control in 9
      cases whose diabetic control was excellent, and in 2 cases who experienced
      hypoglycemic attack during rehabilitation therapy. In these cases, oral
      hypoglycemic agent was reduced from 2 to 1 tablet and insulin from 32 to 21 units
      per day on average. These results indicate that training in the stroke
      rehabilitation moderately improves diabetic control.

PMID- 7825174
TI  - The pattern of respiratory infection in patients with lung cancer.
AB  - We examined retrospectively the pattern of respiratory infection in 579 patients
      with lung cancer admitted to Nagasaki University Hospital during the past 15
      years. A total of 139 patients (24.0%) developed respiratory infection. The rates
      of pulmonary infection associated with large (36.2%) and small cell carcinomas
      (33.6%) were significantly higher than those with squamous cell carcinoma (26.0%)
      and adenocarcinoma (17.3%). Advanced stages of lung cancer were associated with
      higher complication rates (stage I: 6.3%, stage II: 15.9%, stage III: 27.9%, and
      stage IV: 33.8%). Deceased patients showed a significantly higher rate of
      pulmonary infection than alive patients during the period of investigation.
      Isolated organisms in excess of 10(7) cfu/ml in sputum or 10(4) cfu/ml in
      bronchial aspirate were mainly gram-negative bacteria (68.8%), such as
      Haemophilus influenzae, Klebsiella pneumoniae, Enterobacter cloacae,
      Acinetobacter sp. and Pseudomonas aeruginosa. The number of patients infected
      with gram-positive bacteria increased markedly after 1982. Our results suggest
      that a successful control of pulmonary infection associated with lung cancer is
      important in improving the prognosis of lung malignancy.

PMID- 7825175
TI  - Increased plasma gluconeogenic and system A amino acids in patients with
      pancreatic diabetes due to chronic pancreatitis in comparison with primary
      diabetes.
AB  - We examined the plasma amino acid profiles of 17 patients with pancreatic
      diabetes in comparison with those of 14 healthy subjects and 16 patients with
      primary diabetes of similarly poor glycemic control. We also measured fasting
      plasma glucagon and free insulin levels in patients with pancreatic diabetes and
      in those with primary diabetes. The fasting plasma amino acid level was highest
      in patients with pancreatic diabetes. Furthermore, the plasma glucagon level in
      patients with pancreatic diabetes was significantly low, and negative
      correlations were found between glucagon and glucagon-related System A and
      gluconeogenic amino acids. On the other hand, the levels of branched-chain amino
      acids (BCAA) and System L amino acids, which are subjected to change in the state
      of diabetes mellitus, increased in patients with pancreatic diabetes. From the
      above results, we determined that the amino acid profile in patients with
      pancreatic diabetes resembled that in patients with total pancreatectomy. It is
      our opinion that the increases of amino acid levels (gluconeogenic and System A
      amino acids) in patients with pancreatic diabetes is not dependent on
      maldigestion/malabsorption under treatment, but is mainly dependent on glucagon
      deficiency.

PMID- 7825176
TI  - Adriamycin-induced hepatic and myocardial lipid peroxidation and DNA damage, and
      enhanced excretion of urinary lipid metabolites in rats.
AB  - Adriamycin produces clinically useful responses in a variety of human cancers
      including lymphomas, leukemias, and solid tumors. However, the toxicity of
      adriamycin has limited its usefulness. Iron-catalyzed free radical reactions as
      the peroxidation of membrane lipids, inactivation of critical enzymes, and the
      inhibition of DNA, RNA and protein synthesis in heart, liver and kidney have been
      implicated in the toxicity of adriamycin. In order to further assess the role of
      oxidative stress in the toxicity of adriamycin, the effects of adriamycin were
      examined on the urinary excretion of lipid metabolites at 0, 6, 12, 24, 48 and 72
      h post-treatment, and on myocardial and hepatic lipid peroxidation and nuclear
      DNA single strand breaks at 24 h post-treatment following single oral and
      intravenous (i.v.) doses of 10 mg/kg adriamycin. Urinary malondialdehyde (MDA),
      formaldehyde (FA), acetaldehyde (ACT) and acetone (ACON) excretion was
      significantly increased at all time points examined. Following the oral
      administration of adriamycin, maximum excretion of MDA, FA, ACT and ACON of 6.2-,
      2.7-, 3.7- and 2.2-fold relative to control values, respectively, occurred 24 h
      after treatment. However, following the i.v. administration of adriamycin,
      greatest increases in excretion of MDA, FA and ACT reaching 6.9-, 3.3- and 6.3
      fold relative to control values, respectively, were observed 6 h after treatment,
      while the greatest increase in ACON excretion of 4.2-fold relative to control
      values occurred 12 h post-treatment. Following oral and i.v. administration of
      adriamycin, significant increases were observed in myocardial and hepatic lipid
      peroxidation in mitochondrial and microsomal membranes, and myocardial and
      hepatic nuclei DNA single strand breaks 24 h after treatment. The results
      indicate that adriamycin administration induces myocardial and hepatic lipid
      peroxidation which may be responsible for enhanced excretion of urinary lipid
      metabolites as a result of membrane damage, and also induces enhanced DNA damage.
      These effects may be due to adriamycin-induced production of reactive oxygen
      species.

PMID- 7825177
TI  - Cynomolgus monkeys (Macaca fascicularis) in preclinical immune function safety
      testing: development of a delayed-type hypersensitivity procedure.
AB  - A delayed-type hypersensitivity (DTH) test commonly used for humans was adapted
      for use with cynomolgus monkeys (Macaca fascicularis). Pilot experiments showed
      naive animals had poor response rates and inconsistent reactivity to the
      antigens. In an exploratory phase, it was determined that monkeys could be
      experimentally sensitized by immunization with commercially available antigens.
      Animals were then sensitized with various concentrations of diphtheria and
      tetanus toxoids, Candida, and Trichophyton in the dose-response phase. Antigens
      were injected intradermally (i.d.) 3 times over a 7-day period and monkeys were
      tested 14 days after the last injection. Responses were measured 24, 48, and 72 h
      post-challenge, with skin biopsies taken from two animals per group at the 24 h
      interval. Optimal concentrations were 1.2 Lf diphtheria, 6 Lf tetanus, 1000 PNU
      Candida, and 1000 PNU Trichophyton. These concentrations produced the best
      balance between DTH responses, homogeneity of dermal mononuclear cell infiltrate
      and lowest frequency of undesirable skin reactions. Positive responses were seen
      at 24 and 48 h post-challenge and were waning by 72 h. DTH responses were
      inhibited by topical corticosteroids. The final phase of these studies assessed
      whether sensitization of naive animals could be achieved using subcutaneous
      (s.c.) administration of the optimal antigen concentrations. Comparable responses
      to i.d. sensitization were obtained and skin sores did not develop at injection
      sites. These studies show that the DTH test adapted to monkeys was reproducible,
      minimally invasive, did not require sacrifice of the test animal, allowed
      repeated measurements and paralleled the reactions observed in humans.

PMID- 7825178
TI  - Protective effect of metallothionein on intracellular pH changes induced by
      cadmium.
AB  - In order to gain further insight into the protective mechanism of metallothionein
      (MT) against Cd cytotoxicity, the effects of in vivo Zn- or Cd-pretreatment on
      the cytotoxicity and alteration in cellular pH induced by Cd were examined in
      isolated rat hepatocytes and testicular Leydig cells. These pretreatments both
      induced the synthesis of MT in the hepatocytes, but not in the Leydig cells. Both
      pretreatments alleviated Cd cytotoxicity in the hepatocytes. Cd- or Zn
      pretreatment was also effective in preventing Cd-induced cellular acidification
      in hepatocytes but neither pretreatment was effective in Leydig cells. In fact,
      Cd-pretreatment stimulated acidification in Leydig cells. Exposure in vitro of
      hepatocytes from untreated rats to probenecid, an inhibitor of HCO3-/Cl-
      exchange, also ameliorated Cd-induced cellular acidification, suggesting an
      involvement of HCO3-/Cl- exchange in the preventive action of MT against Cd
      induced acidification. These results suggest that Cd cytotoxicity in various
      cells may be initiated by alterations in plasma membrane ion transport systems
      such as the HCO3-/Cl- exchange and consequential cellular acidification.
      Induction of MT, therefore, may prevent Cd cytotoxicity, at least in rat
      hepatocytes, by preventing an alteration in ion transport at the plasma membrane
      as well as by intracytoplasmic binding of the metal molecules.

PMID- 7825180
TI  - Time-course of toxicity of reactive sulfonamide metabolites.
AB  - It has been suggested, on the basis of work in cell-free systems, that
      sulfonamide hydroxy-lamines are metabolized to nitroso metabolites which may be
      the proximate toxins mediating sulfonamide hypersensitivity reactions. We
      performed time-course experiments investigating the toxicity of the hydroxylamine
      and nitroso derivatives of sulfamethoxazole to investigate this hypothesis. The
      nitroso derivative of sulfamethoxazole was significantly more toxic than the
      hydroxylamine derivative (P < 0.05). When the LC50 was compared over time, there
      was a significant decrease in the LC50 of the hydroxylamine of sulfamethoxazole
      over time, while there was no change in the LC50 of the nitroso derivative. There
      was an equivalent reduction in toxicity demonstrated when the hydroxylamine or
      nitroso derivatives were co-incubated with glutathione. This supports the role of
      the nitroso as a proximate toxin mediating sulfonamide hypersensitivity reactions
      and suggests an explanation for the high rate of adverse reactions to
      sulfonamides among patients with AIDS.

PMID- 7825179
TI  - Effect of atropine and bispyridinium oximes on respiratory and circulatory
      function in guinea-pigs poisoned by sarin.
AB  - During the past decade the oxime HI 6(1-[[[4
      (aminocarbonyl)pyridinio]methoxy]methyl]-2- [(hydroxyimino)methyl] pyridinium
      dichloride) was shown to improve survival in nerve agent poisoning (in
      combination with atropine). Recent studies indicate, that HLo 7 (1-[[[4
      (aminocarbonyl)pyridinio]methoxy]methyl]-2,4-bis [(hydroxyimino)methyl]
      pyridinium diiodide or dimethanesulfonate) is also an effective antidote in nerve
      agent poisoning but, with both oximes, data on restoration of respiration and
      circulation are scarce. The ability of HLo 7 or HI 6 with atropine to improve the
      respiratory and circulatory function in sarin-poisoned guinea-pigs was therefore
      investigated. Female Dunkin-Hartley guinea-pigs were anaesthetised with urethane
      (1.8 g/kg) and the arteria carotis, vena jugularis and trachea were cannulated.
      After baseline measurements the animals received 100 or 200 micrograms/kg sarin,
      and 2 min later the antidotes (all i.v.): 10 mg/kg atropine sulfate or a
      combination of atropine and HLo 7 or HI 6 (30 mumol/kg, each). Respiratory and
      circulatory parameters were recorded for the whole experimental period of 60 min
      or until the death of the animal. Brain and diaphragm acetylcholinesterase (AChE)
      activity was determined in each animal after the experiment. Poisoning by sarin
      resulted in a rapid respiratory arrest within 5 min. Atropine treatment was only
      partially effective in improving respiration after 100 micrograms/kg sarin but
      was ineffective after 200 micrograms/kg sarin. Therapy of sarin-poisoned animals
      with atropine plus oxime further improved respiration to various extents,
      restored circulation and increased survival time, HLo 7 being more effective than
      HI 6. Diaphragm and brain AChE were reactivated by HLo 7 and, to a minor extent,
      by HI 6. The results of this investigation suggest, that at equimolar doses (30
      mumol/kg) the new bispyridinium dioxime HLo 7 has a higher therapeutic efficacy
      in sarin-poisoned guinea-pigs when compared to HI 6 (both in combination with
      atropine).

PMID- 7825181
TI  - Effect of piroxicam on the nephrotoxicity induced by ochratoxin A in rats.
AB  - Ochratoxin A (OTA) is a mycotoxin which contaminates animal feed and human food
      and is nephrotoxic for all animal species studied so far. It binds to plasma
      proteins and is transported into target organs, especially the kidney. An attempt
      to prevent its toxic effects has been made using piroxicam, a non-steroidal anti
      inflammatory drug (NSAID). Piroxicam also binds strongly to plasma proteins and
      our hypothesis is that this drug could stop OTA-binding and transport into target
      organs, thereby preventing its nephrotoxicity. Our experiments on rats given OTA
      (289 micrograms/kg/48 h for 2 weeks) show that piroxicam prevents the enzymuria
      induced by OTA and increases renal elimination of OTA. In vivo, piroxicam could
      prove useful in preventing the chronic effects of ochratoxin A, mainly
      nephrotoxicity, at doses 5 mg/kg/48 h, which were not found to be nephrotoxic in
      experimental animals.

PMID- 7825182
TI  - Mitochondrial Ca2+ overload in primary cultures of rat renal cortical epithelial
      cells by cytotoxic concentrations of cyclosporine: a digitized fluorescence
      imaging study.
AB  - Cyclosporine (CsA) has been reported to disrupt Ca2+ efflux from mitochondria,
      which suggests that CsA interference with Ca2+ homeostasis may be related to its
      nephrotoxicity. Therefore, the purpose of this study was (1) to determine
      intracellular free Ca2+ concentration ([Ca2+]i) and mitochondrial free Ca2+
      concentration ([Ca2+]m) after primary cultures of rat renal cortical epithelial
      cells were exposed to cytotoxic concentrations of CsA; and (2) to explore the
      role of disruption of intracellular and mitochondrial Ca2+ homeostasis in CsA
      induced cytotoxicity. [Ca2+]i in single kidney cells was examined by digitized
      fluorescence imaging (DFI) of the Ca2+ fluorescent probe, fura-2, and [Ca2+]m in
      single cells was observed by DFI of fura-2 entrapped in mitochondria after
      selective permeabilization of plasma membrane and other non-mitochondrial
      organelles by digitonin. Mitochondrial membrane potential (delta psi) in single
      kidney cells was examined by rhodamine 123 (Rh-123) with DFI. Intracellular ATP
      in kidney cells was determined by a HPLC method. CsA resulted in an elevation in
      [Ca2+]i and [Ca2+]m, dissipation of delta psi and depletion of ATP in a dose- and
      time-dependent manner. The elevation of [Ca2+]i and [Ca2+]m and depletion of ATP
      preceded CsA-induced cytotoxicity in kidney cells as measured by lactate
      dehydrogenase (LDH) leakage. We conclude that CsA-induced alterations in
      mitochondrial Ca2+ homeostasis and a subsequent loss of energy supply may play a
      key role in CsA-induced cytotoxicity in primary cultures of rat renal cortical
      epithelial cells.

PMID- 7825183
TI  - Effects of meso-2,3-dimercaptosuccinic acid or 2,3-dimercaptopropane 1-sulfonate
      on beryllium-induced biochemical alterations and metal concentration in male
      rats.
AB  - The effects of two chelating agents, meso-2,3-dimercaptosuccinic acid (DMSA) and
      2,3-dimercaptopropane 1-sulfonate (DMPS) on the mobilization, distribution,
      hepatic and hematopoietic toxicity of beryllium were compared in male rats
      exposed to beryllium. Animals were exposed to beryllium nitrate (0.5 mg/kg,
      orally, daily 5 days/week) for 21 days. Twenty-four hours after the last dose
      they were injected with a chelating agent (DMSA or DMPS) (25 or 50 mg/kg, twice
      daily for 5 days). The administration of DMSA and DMPS at a dose of 50 mg/kg
      marginally elevated the fecal excretion of beryllium. DMPS was effective in
      depleting beryllium from the liver, spleen and kidneys. However, DMPS (50 mg/kg)
      results in the redistribution of beryllium to blood. Beryllium-induced inhibition
      of hepatic alkaline phosphatase and hepatic adenosine triphosphatase (ATPase)
      were restored considerably with the chelating agents. Also, hepatic and renal
      histopathological lesions were less marked in rats treated with DMPS (50 mg/kg)
      compared with those treated with beryllium per se and DMSA. These effects were
      more prominent at the 50-mg/kg dose of chelating agents than at 25 mg/kg. These
      results suggest that treatment with DMPS has some beneficial effects in
      experimental beryllium intoxication.

PMID- 7825184
TI  - The effects of acute exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin on glioma
      specific cytotoxic T-cell activity in Fischer 344 rats.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is one of the most potent
      environmental immunomodulating agents identified so far. Historically, mice have
      been used to model mammalian immunobiology and most of the data gathered on the
      immunotoxicity of TCDD has been obtained from studies with mice. However, rats
      have been used more extensively in toxicological research to establish human risk
      assessment criteria. A need exists, therefore, to develop a database using the
      rat model in immunotoxicology so that complete animal toxicity studies can be
      conducted. We have treated female Fischer 344 rats with a single i.p. dose of
      0.3, 3.0, or 30.0 micrograms/kg TCDD or corn oil vehicle and examined cytotoxic T
      cell (CTL) activities 24 days following treatment. Syngeneic in vivo tumor
      specific CTLs were generated that model cell-mediated immune reactions against
      neoplastically transformed self antigens. RT2, a virally-induced Fischer 344 rat
      glioma, and D74, a ethylnitrosurea-induced Fischer 344 rat glioma were used as
      targets. This immunological parameter was compared to body, thymic, and liver
      weights as well as liver ethoxyresorufin deethylase (EROD) activity on day 24
      post-TCDD treatment. The results indicate that Fischer 344 rats are very
      sensitive to TCDD as indicated by severe thymic atrophy and EROD induction at all
      three doses. In contrast, CTL activity was only marginally affected by these same
      doses of TCDD with only a modest suppression noted at the highest dose. These
      results indicate that the CTL response in rats may not be useful in
      characterizing the effects of this xenobiotic on immunocompetence in the rat.

PMID- 7825185
TI  - Effect of TNF alpha production inhibitors BRL 61063 and pentoxifylline on the
      response of rats to poly I:C.
AB  - BRL 61063 is a novel xanthine phosphodiesterase (PDE) type IV inhibitor with
      selective inhibitory activity for tumor necrosis factor (TNF) alpha production.
      This compound inhibits TNF alpha production by activated human blood monocytes in
      vitro and in animal models of endotoxemia and influenza infection. Inhibition of
      TNF alpha may be beneficial in many diseases; however, little is known about
      potential adverse effects of such inhibition on host defense. In an ex vivo
      study, we examined the effect of BRL 61,063 on the microbicidal and tumoricidal
      activity of pulmonary lavage cells during a local inflammatory response in rats
      challenged with Poly I:C. Pentoxifylline, a PDE inhibitor which also blocks TNF
      alpha production, was used for comparison. Treatment with BRL 61063 or
      pentoxifylline did not block the inflammatory response to Poly I:C or the
      activation of bronchoalveolar lavage (BAL) cells but reduced the level of
      tumoricidal activity attained. At the dosages used, pentoxifylline was more
      inhibitory than BRL 61063. Drug treatment did not prevent further stimulation of
      tumoricidal activity by LPS in vitro. LPS-stimulated cells from BRL 61063-treated
      rats reached a level of activation similar to the control group while the LPS
      stimulated activity of BAL cells from pentoxifylline treated rats remained lower
      than control. Although pentoxifylline was more inhibitory for tumoricidal
      activity than BRL 61063, the latter was a more potent inhibitor of TNF alpha
      release as measured in vivo in LPS-challenged rats. This finding indicates that
      TNF alpha is not the main mediator involved in the activation of pulmonary
      macrophage tumoricidal function. Treatment with either BRL 61063 or
      pentoxifylline had little or no effect on the Poly I:C-induced candidacidal
      activity of BAL cells indicating that these compounds are unlikely to compromise
      non-specific host defense against infection.

PMID- 7825186
TI  - A hypothesis for cyanide-induced tonic seizures with supporting evidence.
AB  - A possible relationship among cyanide-induced convulsions, calmodulin, nitric
      oxide and protein kinase C was investigated in mice. The ED50 value of cyanide as
      measured by induction of tonic seizures was significantly increased in a dose
      dependent manner when mercuric chloride (0.5 or 5.0 nmol/body), gangliosides
      (GGS) (90 nmol/body), a protein kinase C inhibitor or trifluoperazine (TFP) (45
      or 90 nmol/body), a calmodulin inhibitor were preinjected
      intracerebroventricularly (i.v.t.) and NG-nitro-L-arginine (NNA) (300 mg/kg), a
      nitric oxide (NO) synthase inhibitor was preinjected intraperitoneally (i.p.) in
      mice. These results suggest that protein kinase C, calmodulin, and NO dependent
      cyclic guanosine monophosphate (GMP) dependent enzymes may contribute to the
      induction of convulsions. In contrast, 2,4-dinitrophenol (DNP) (50 nmol/body,
      intracerebroventricularly (i.v.t.), an uncoupler of oxidative phosphorylation
      significantly decreased the ED50 value of cyanide. In addition, DNP (100
      nmol/body, i.v.t.) produced a severe tonic seizure in all of the treated mice.
      These indicate that adenosine triphosphate (ATP) depletion may also contribute in
      part to the development of cyanide-induced convulsions.

PMID- 7825187
TI  - CYP1 induction, binding to the hepatic aromatic hydrocarbon receptor and
      mutagenicity of a series of 11-alkoxy cyclopenta[a]phenanthren-17-ones: a
      structure activity relationship.
AB  - A series of four 11-alkoxy cyclopenta[a]phenanthren-17-ones, ranging from the
      methoxy to the butoxy derivative, has been synthesised in order to investigate
      the effect of the size of the 11-substituent on the mutagenicity and ability of
      these compounds to induce hepatic CYP1 activity in rats. The latter was monitored
      by using as diagnostic probes methoxy and ethoxy-resorufin, and immunologically
      in Western blots employing anti-CYP1A1 antibodies. All four members of the series
      induced both CYP1A1 and CYP1A2 activities and apoprotein levels, but the methoxy-
      and ethoxy-CPP-17-ones were clearly the most potent. Of the four isomers, only 11
      methoxy-CPP-17-one displaced 3H-TCDD from the cytosolic Ah receptor. Similarly
      only 11-methoxy-CPP-17-one elicited a positive mutagenic response in the Ames
      test in the presence of an Aroclor 1254-induced activation system. The relevance
      of these findings to the carcinogenicity of these compounds in the mouse skin
      painting model is discussed.

PMID- 7825189
TI  - Effects of ochratoxin A upon early and late events in human T-cell proliferation.
AB  - We have investigated the effect of ochratoxin A (OA) on both early and late
      events during activation of human T lymphocytes. As early activation parameters
      we chose to measure both changes in intracellular Ca2+ levels and the activity of
      protein kinase C following the triggering process. Our results demonstrate that
      concentrations of OA that inhibit overall activation had no effect neither on the
      absolute levels nor on the duration of the Ca2+ response. Furthermore, PKC
      activity as measured by phosphorylation of two specific cytosolic substrate
      substrate proteins, was also unaffected. However, when the cells were
      prestimulated for 48 h to measure effects on late events in the activation
      cascade, addition of graded concentrations of ochratoxin A down to 6.4 microns
      completely inhibited the DNA synthesis. This shows that ochratoxin A is able to
      block DNA synthesis efficiently even if the activation process has been running
      for 48 h in advance. To investigate whether the inhibitory effect on DNA
      synthesis could be ascribed to inhibition of protein synthesis, we carried out
      experiments to measure protein synthesis both in resting and activated T-cells.
      In resting T-cells protein synthesis was nearly abrogated by 12.5 microM
      ochratoxin A, but only minor effects were observed in stimulated cells. The low
      impact of ochratoxin A on protein synthesis in activated cells may indicate that
      other mechanisms than just a general inhibition of protein synthesis are
      operating.

PMID- 7825188
TI  - Behavioural effects of norpethidine, a metabolite of pethidine, in rats.
AB  - This study investigated behavioural effects of the toxic pethidine metabolite,
      norpethidine, in rats and its interactions with reserpine, apomorphine and
      physostigmine. Following intraperitoneal administration, brain concentrations of
      norpethidine reached a plateau after 20-40 min and remained elevated for 2 h. In
      the dose range 0.06-0.18 mmol/kg, norpethidine induced myoclonic jerks, a
      characteristic splayed posture, and episodes of exaggerated shivering. Forward
      locomotion, grooming, yawning and rearing were suppressed. Seizures and reverse
      locomotion occurred occasionally. Administration of reserpine 1 h prior to
      norpethidine, or of apomorphine or physostigmine 15 min after norpethidine, did
      not alter the norpethidine-induced behaviours; neither did norpethidine block the
      effects of apomorphine or physostigmine. The characteristic profile of behaviours
      induced by norpethidine make this toxicant readily amenable to animal studies.
      Our results indicate that its mechanism of action is unlikely to involve
      dopaminergic or cholinergic pathways.

PMID- 7825190
TI  - The effect of implantation of osmotic pumps on rat thyroid hormone and
      testosterone levels in the plasma, an implication for tissue 'S' phase studies.
AB  - In order to monitor the effect of the procedures required to s.c. implant osmotic
      pumps into rats on plasma thyroid and testosterone hormone levels, male Fischer
      344 rats (8-10 weeks old) were divided into six groups of 10 rats and the groups
      treated in the following manner: (1) controls housed 5 per cage; (2) controls
      housed individually; (3) animals anaesthetised for surgery and individually
      housed; (4) anaesthetised, sham operated and individually housed; (5)
      anaesthetised, s.c. implanted with osmotic pumps containing saline and
      individually housed; (6) anaesthetised, s.c. implanted with osmotic pumps
      containing 5-bromo 2-deoxyuridine (BRDU) and individually housed. Four days after
      performing the surgery the study was terminated and the level of hormones in the
      plasma determined by radio immunoassay (RIA). Tri-iodothyronine (T3) and
      thyroxine (T4) plasma levels (free and total) were significantly decreased with
      each additional step in the procedure used for the s.c. implantation of an
      osmotic pump containing BRDU, when compared with the individually housed
      controls. Similarly, testosterone plasma levels were significantly decreased by
      the s.c. implantation of osmotic pumps, implying a 'stress' response might occur
      following implantation. These observations might need to be considered by
      investigators when performing toxicological research which, as part of the study,
      uses osmotic pumps for the delivery of the nucleotide precursor required for
      monitoring cells in 'S' phase.

PMID- 7825191
TI  - The effect of sodium fluoride at prophylactic and toxic doses on renal structure
      and function in the isolated perfused rat kidney.
AB  - To assess the renal effects of fluoride, isolated rat kidneys were perfused in
      single pass mode for 120 min. Five, 15 and 50, as well as 150, 500 and 1500 mumol
      NaF were administered 60, 80 and 100 min after starting the perfusion,
      respectively. Kidneys were perfused with constant pressure (100 mmHg). The
      perfusate consisted of a substrate supplemented Ringer solution containing
      hydroxy ethyl starch (HES) to produce isoncotic conditions. Concentrations below
      500 mumol/l NaF did not induce major changes in the main parameters of renal
      function. Only upon admixture of the highest concentration of 1500 mumol/l NaF
      severe changes in renal function could be observed, resulting in complete anuria
      and a drastic reduction of renal perfusion to 5% of control, associated with a
      cessation of glomerular filtration. Due to the lack in tubular load, tubular
      reabsorptive processes inevitably declined to zero. The morphological analysis of
      kidneys exhibited to 500 mumol/l NaF revealed the occurrence of vesicular
      material within the urinary space. These vesicles could electron microscopically
      be identified as membrane enclosed material of podocytic origin. The interstitium
      was widened. Upon admixture of 1500 mumol/l NaF, kidneys responded with a
      decrease of the interstitial space. Moreover, epithelial cell swelling, hydropic
      degeneration of all proximal and distal tubular segments, bleb formation and
      intraluminal casts were observed frequently. Glomerular capillaries were filled
      with fine precipitates and their endothelium was severely damaged. The results of
      our studies in the isolated perfused rat kidney (IPRK) model clearly demonstrate
      a direct dose dependent acute nephrotoxic effect of NaF only for extremely high
      doses, which, however, may be reached in human cases of severe fluoride
      intoxication. On the contrary, for low fluoride doses, especially for those
      concentrations occurring in human plasma upon cariesprophylactic intake of
      fluorides, no signs of direct acute nephrotoxic action could be observed in the
      IPRK model.

PMID- 7825192
TI  - Induced regenerative cell proliferation in livers and kidneys of male F-344 rats
      given chloroform in corn oil by gavage or ad libitum in drinking water.
AB  - These studies were designed to establish the dose response relationships for the
      induction of cytolethality and regenerative cell proliferation in the liver and
      kidneys of male F-344 rats given chloroform by gavage or in drinking water. Rats
      were administered oral doses of 0, 10, 34, 90 or 180 mg/kg/day chloroform
      dissolved in corn oil by gavage for 4 days or for 5 days/week for 3 weeks. A
      second group of rats was given chloroform ad libitum in the drinking water at
      concentrations of 0, 60, 200, 400, 900 or 1800 ppm for 4 days or 3 weeks.
      Bromodeoxyuridine (BrdU) was administered via an implanted osmotic pump 3.5 days
      prior to necropsy to label cells in S-phase. Cells having incorporated BrdU were
      visualized in tissue sections immunohistochemically and the labelling index (LI)
      evaluated as the percentage of S-phase cells. Rats treated with 90 or 180
      mg/kg/day by gavage for 4 days had mild to moderate degeneration of renal
      proximal tubules and centrilobular hepatocytes. These alterations were absent or
      slight after 3 weeks of treatment. LI were increased in the kidney cortex only in
      the rats treated with 180 mg/kg/day for 4 days. A dose-dependent increase in LI
      was seen in rat liver after 4 days of treatment with 90 and 180 mg/kg/day by
      gavage, but the LI remained elevated after 3 weeks of treatment only at the 180
      mg/kg/day dose. When chloroform was administered in the drinking water, no
      microscopic alterations were seen in the kidneys after 4 days of treatment. As a
      general observation, rats treated for 3 weeks with 200 ppm chloroform and greater
      had slightly increased numbers of focal areas of regenerating renal proximal
      tubular epithelium and cell proliferation than were noted in the controls, but no
      clear dose response relationship was evident. However, the overall renal LI was
      not increased at any dose or time point. Similarly, only mild hepatocyte
      vacuolation was observed in rats given 1800 ppm chloroform in the water for 3
      weeks with no increase in the hepatic LI at any time point, even though the rats
      were consuming chloroform at a rate of 106 mg/kg/day at the 1800 ppm drinking
      water concentration. These data indicate more severe hepatic and renal toxicity
      when chloroform is administered by gavage than in the drinking water and a
      different pattern of regenerative proliferation in the kidney.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 7825193
TI  - Human chorionic gonadotropin protects Leydig cell function against 2,3,7,8
      tetrachlorodibenzo-p-dioxin in adult rats: role of Leydig cell cytoplasmic
      volume.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) alters testicular steroidogenesis and
      reduces Leydig cell volume and number; however, human chorionic gonadotropin
      (hCG) stimulates testosterone production, increases the number and volume of
      Leydig cells and prevents TCDD's inhibition of testosterone production. The
      objective of this study was to determine if hCG protects Leydig cell function by
      maintaining sufficient Leydig cell cytoplasmic volume in TCDD-treated rats.
      Adult, male Sprague Dawley rats were divided into six treatment groups. Half of
      the animals received TCDD in corn oil (50 micrograms/kg body wt) and half
      received corn oil alone on Day 7 only. Additionally the rats received daily
      treatment of saline for 14 days, saline for 7 days and then hCG for 7 days, or
      hCG for 14 days. Rats were sacrificed on Day 14 and tissues collected. The
      decapsulated left testes were incubated in Eagles MEM for 2 h to determine basal
      production of testosterone and for 2 additional hours after the addition of hCG
      (100 IU) to the culture media. The right testis was evaluated by stereology to
      determine the volume of Leydig cells. Body weight was reduced (P < 0.01) in each
      TCDD-treated group; whereas, testicular weight was not affected by TCDD or hCG
      treatment. hCG prevented the TCDD-induced reduction in prostate and seminal
      vesicles weights. TCDD reduced the total volume of Leydig cell cytoplasm in
      saline-treated rats, but hCG eliminated the TCDD-induced reduction in Leydig cell
      cytoplasmic volume. hCG prevented the TCDD-induced reduction in Leydig cell
      function for both the 7- and 14-day treatments. Variation in the total volume of
      Leydig cell cytoplasm induced by the various treatment combinations was
      positively correlated with stimulated testosterone production in vitro (r =
      0.486; P < 0.01) and the weight of the androgen sensitive organs (seminal
      vesicles, r = 0.562, P < 0.01; prostate, r = 0.380, P < 0.05). These data support
      the hypothesis that hCG prevents the TCDD-reduced Leydig cell function by
      maintaining sufficient Leydig cell cytoplasm and organelle content.

PMID- 7825194
TI  - Witnessed suicides.
AB  - Suicides that take place in the presence of others have not been the topic of
      systematic scientific inquiry. The so-called witnessed suicides account for a
      small percentage of all suicides but offer a unique view into the dynamics of
      self-destructive behavior. An epidemiologic and forensic description of 50
      witnessed suicides drawn from a 15-year series of over 1,000 cases is presented.
      A taxonomy is developed based on the role played by the witness and related to
      previous work on self-destructive behavior and its motivation. Brief vignettes
      are used to illustrate some of the interpersonal dynamics associated with these
      deaths.

PMID- 7825195
TI  - An evaluation of a school-based suicide awareness intervention.
AB  - This study employed a self-report questionnaire in a Solomon four-groups design
      to assess the efficacy of suicide intervention classes in achieving their
      instructional objectives. Because adolescents are often the first to know of a
      peer's suicidal thoughts or plans, the goal of the classes was to increase the
      likelihood that students who come into contact with potentially suicidal peers
      can more readily identify them and will be consistently inclined to take
      responsible action on their behalf. Students who participated in the classes as
      compared to controls showed significant gains in relevant knowledge about
      suicidal peers and significantly more positive attitudes toward help seeking and
      intervening with troubled peers. Results of this study will be used to strengthen
      components of the lessons aimed at enhancing the likelihood of performance of
      responsible interventions.

PMID- 7825196
TI  - A life course theory of suicide risk.
AB  - The three distinct suicide cycles reported since the late 19th century have been
      explained using sociological and biological theories. Despite their obvious
      differences, both theories operate through motivation. Like other aspects of
      suicide, however, such cycles can also be explained by opportunity. Analysis of
      recent findings on age- and sex-specific suicide cycles illustrates a fundamental
      confound of motivation and opportunity, and underscores the need for a theory of
      suicide that is based on risk (risk = motivation x opportunity), and that is
      situated in a framework of age- and sex-specific life course contingencies.

PMID- 7825197
TI  - Suicide as social logic.
AB  - Although suicide is not viewed as a mental disorder per se, it is viewed by many
      if not most clinicians, researchers, and lay people as a real or natural symptom
      of depression. It is at least most typically seen as the unfortunate, severe, yet
      logical end result of a chain of negative self-appraisals, negative events, and
      hopelessness. Extending an approach articulated by the early French sociologist
      Gabriel Tarde, in this paper I argue that suicide is merely an idea, albeit a
      very bad one, having more in common with societal beliefs and norms regarding
      such things as divorce, abortion, sex, politics, consumer behavior, and fashion.
      I make a sharp contrast between perturbation and lethality, concepts central to
      Edwin S. Shneidman's theory of suicide. Evidence supportive of suicide as an idea
      is discussed based on what we are learning from the study of history and culture,
      and about contagion/cluster phenomena, media/communication, and choice of method.
      It is suggested that certain individuals are more vulnerable to incorporate the
      idea and act of suicide into their concepts of self, based on the same principles
      by which ideas are spread throughout society. Just as suicide impacts on society,
      so does society impact on suicide.

PMID- 7825198
TI  - A cluster of suicides at a London psychiatric unit.
AB  - In an epidemiologically based study, a spate of 14 suicides among current
      patients of a London psychiatric unit was investigated. Statistical analysis
      showed it to be a discrete cluster of suicides, rather than a chance occurrence.
      There was no evidence of direct linkage or "contagion" between the suicides.
      Thirteen of the patients suffered from severe, chronic mental illness and all but
      2 had been known to the psychiatric unit for at least a year. Twelve used violent
      methods, in 8 cases jumping from a high place. Although no definite cause for the
      cluster could be established, it coincided with a period of uncertainty
      concerning the future of the hospital and with changes in and absenteeism of
      senior medical staff.

PMID- 7825199
TI  - Linking work and domestic problems with police suicide.
AB  - We reviewed the records of 134 police officers who had undergone their first
      fitness-for-duty evaluation at our center. Fifty-five percent admitted to
      previous suicide attempts. We examined possible contributing factors. A logistic
      regression model correctly classified 79.1% of subjects as to whether or not they
      attempted suicide. Results indicated that officers reporting marital problems
      were 4.8 times more likely to have attempted suicide, and 6.7 times more likely
      if they had been suspended. Interestingly, complaints of being administratively
      harassed were associated with a lower likelihood that an officer would attempt
      suicide. Variance explained due to age, race, gender, and substance use was
      nonsignificant.

PMID- 7825200
TI  - The frequency of suicide in individual Danish birth cohorts, 1922-1991.
AB  - In recent years many suicidologists have based their epidemiological studies on
      suicide on theories assuming that people born within the same period of time will
      follow the same suicidal patterns throughout their lives, and that variations in
      the annual rate of suicide will, therefore, reflect systematic differences
      between cohorts. Cohort analysis carried out on Danish data showed, however, that
      although some differences could be found as to the course of events during the
      life span of the cohorts and also when the material was adjusted for sex, no
      significant differences could be found between various birth cohorts in the total
      rates of suicide. The authors argue that the reason for this is that a cohort
      effect is only one of three dimensions of an analytical tool, namely, Age-Period
      Cohort (APC) analysis, and that the balance between the three effects changes
      over time.

PMID- 7825201
TI  - Relationships between suicidal behavior and personality types.
AB  - This study examined the hypotheses that introversion in general and the
      introverted-intuitive-feeling-perceiving (INFP) type as measured by the Meyers
      Briggs Type Indicator are related to suicidal ideation and behaviors. Analyses of
      data from 330 university students found four interactive suicidal behavior risk
      models: introverted-perceiving (IP) (females); introverted-sensing-feeling (ISF)
      (males); introverted-intuitive-perceiving (INP) (males); extraverted-intuitive
      judging (ENJ) (males). Study findings were interpreted in terms of implications
      for risk assessment and intervention.

PMID- 7825202
TI  - Fall from power: suicide of an executive.
AB  - An influential corporate executive apparently killed himself and two others when
      faced with public exposure and perhaps imprisonment for illegal use of his
      corporate position to raise money for political and charitable causes he favored.
      Clinical and psychological descriptions of such cases are rare. Because an
      extensive psychological autopsy enabled a detailed description of this case, it
      is presented with the aim of shedding light on a type of suicide that needs to be
      understood.

PMID- 7825203
TI  - The transition from inpatient to outpatient care.

PMID- 7825204
TI  - Hepatitis C virus infection in hypogammaglobulinemic patients receiving long-term
      replacement therapy with intravenous immunoglobulin.
AB  - BACKGROUND: Hepatitis C virus (HCV) seroconversion and viremia have been reported
      in patients treated with intravenous immunoglobulin (IVIG). STUDY DESIGN AND
      METHODS: A prevalence study was conducted to evaluate the rate of HCV infection
      in patients undergoing long-term treatment with IVIG. Fifty-four patients with
      congenital or acquired hypogammaglobulinemia treated with IVIG at 300 to 400 mg
      per kg every 14 to 21 days for a mean of 6.6 years were enrolled for clinical and
      biochemical examination. The type of IVIG preparation (type 1 only, type 2 only,
      or other products) administered to each patient was recorded. Antibodies to HCV
      were measured by enzyme-linked immunosorbent assay and immunoblotting; HCV RNA
      was detected by nested polymerase chain reaction. RESULTS: Anti-HCV was detected
      in 31 patients (57.4%) and HCV RNA was found in 5 patients (9.2%), all of whom
      were anti-HCV-positive. Abnormal alanine aminotransferase (ALT) levels were found
      in 10 patients (18.5%). Circulating HCV RNA (p = 0.01) and elevated ALT (p =
      0.01) correlated significantly with anti-HCV positivity. Moreover, the rates of
      anti-HCV positivity and of ALT elevation were significantly higher among patients
      treated with type 1 IVIG and other products than among those receiving type 2
      IVIG (p < 0.001 and p = 0.05, respectively). CONCLUSION: Anti-HCV positivity and
      viremia were frequently observed. The significant correlation between the
      detection of HCV RNA, the elevation of ALT, and positivity for anti-HCV suggests
      HCV infection. Exclusion of anti-HCV-positive donors and of anti-HCV-positive
      IVIG lots should improve the safety of IVIG.

PMID- 7825205
TI  - Hepatitis C virus RNA in factor VIII concentrates.
AB  - BACKGROUND: Hepatitis C virus (HCV) RNA was measured in commercial factor VIII
      concentrates, that is, antihemophilic factor (human) (AHF), to allow the
      retrospective evaluation of the effect of various virus-inactivation procedures.
      The impact on AHF of recent anti-HCV screening of plasma was also investigated.
      STUDY DESIGN AND METHODS: A total of 183 lots of AHF made by six United States
      licensed manufacturers from anti-HCV-unscreened (1976-1991) or screened (1992
      1993) plasma were examined. Detection and quantitation of HCV RNA were achieved
      by reverse transcription and nested polymerase chain reaction at limiting
      dilution. Anti-HCV in AHF was also measured. RESULTS: Earlier AHF lots subjected
      to non-virus-inactivated treatment (36 lots), dry heat (11 lots), or heating in n
      heptane (4 lots) had relatively high levels of HCV RNA. Most (76%) wet-heated
      lots prepared before 1992 contained HCV RNA. No HCV RNA was detected in lots
      purified by immunoaffinity and subsequently heated or solvent/detergent (S/D)
      treated. However, trace levels of HCV RNA were detected in S/D-treated lots made
      by one of four manufacturers before 1992. Since the start of anti-HCV plasma
      screening in 1992, 38 lots prepared by six manufacturers were negative for HCV
      RNA. Prevalence of anti-HCV was also associated with earlier concentrates and
      with S/D-treated lots from that single manufacturer. CONCLUSION: Anti-HCV
      screening of plasma by manufacturers in conjunction with current virus
      inactivation procedures, wet-heating or S/D treatment (either process with or
      without affinity purification), appears to reduce HCV RNA to undetectable levels
      in AHF.

PMID- 7825206
TI  - Effect of filtration of platelet concentrates on the accumulation of cytokines
      and platelet release factors during storage.
AB  - BACKGROUND: Platelet transfusions are frequently accompanied by febrile
      nonhemolytic transfusion reactions. These may be due, in part, to the release of
      cytokines interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6), interleukin 8 (IL
      8), and tumor necrosis factor alpha (TNF-alpha) by white cells (WBCs) into the
      plasma during storage of platelet concentrates (PCs). Acting as endogenous
      pyrogens, these agents may induce inflammatory responses. STUDY DESIGN AND
      METHODS: This study proposed to determine if WBC reduction in PCs by filtration
      significantly reduced the levels of cytokines normally generated during storage
      of unfiltered PCs up to 5 days. Serotonin, platelet-derived growth factor (PDGF
      AB), and von Willebrand factor levels were also assessed to establish whether or
      not filtration or storage elicited significant platelet activation and granule
      release. RESULTS: Filtration significantly reduced total WBC counts by 99.1
      percent before storage (p < 0.001) without affecting total platelet counts.
      Compared to unfiltered PCs, filtration prevented a rise in the levels of each
      cytokine by Day 3 for IL-1 beta (27.7 vs. 0.6 pg/mL; p < 0.05), IL-6 (114.2 vs.
      0.4 pg/mL; p < 0.001), and IL-8 (4.2 vs. 0.02 ng/mL; p < 0.001). By Day 5,
      further increases in the levels of all cytokines were noted in unfiltered PCs,
      but Day 0 levels remained in filtered PCs (IL-1 beta: 105.4 vs. 0.4 pg/mL, p <
      0.001; TNF-alpha: 42.2 vs. 7.5 pg/mL, p < 0.025; IL-6: 268.8 vs. 0.4 pg/mL, p <
      0.001; and IL-8: 7.6 vs. 0.02 ng/mL, p < 0.001). From Day 0 to Day 5, there were
      significant increases in serotonin (21.3 vs. 6.3 ng/mL, p < 0.05), PDGF-AB (72.6
      vs. 25.8 ng/mL, p < 0.001), and von Willebrand factor (4.7 vs. 2.7 IU/mL, p <
      0.05) in unfiltered PCs, with similar increased levels being observed in filtered
      PCs during storage. CONCLUSION: These data indicate that the accumulation of high
      levels of cytokines in stored PCs could be prevented by WBC-reduction filtration
      of PCs without the induction of significant platelet activation or granule
      release. As cytokines have the potential to induce febrile nonhemolytic
      transfusion reactions in patients, the transfusion of WBC-reduced PCs would be
      expected to reduce the frequency and severity of such reactions.

PMID- 7825207
TI  - In vitro and in vivo effects of prestorage filtration of apheresis platelets.
AB  - BACKGROUND: The effect of prestorage filtration on the quality of apheresis
      platelet concentrates stored for transfusion is undetermined. STUDY DESIGN AND
      METHODS: Investigation of 11 plateletpheresis components used a concurrent paired
      study design. On the day of collection, each component was equally divided into
      two suspensions; one half was filtered, and the other half was not. Each
      suspension was stored for 5 days. In vitro testing was performed on the day of
      collection (Day 0) for cell counts and on Day 5 for measurements of lactate,
      glucose, blood gases, pH, platelet ATP, hypotonic stress ratio, extent of shape
      change in response to ADP, tissue necrosis factor alpha, interleukin 8,
      interleukin 1 alpha, interleukin 1 beta, interleukin 6, and platelet surface
      glycoproteins by flow cytometry. At the end of the 5-day period, a sample was
      taken from each of the two suspensions, radiolabeled with either 51Cr or 111In,
      and transfused concurrently. Posttransfusion samples were drawn for measurements
      of recovery and platelet survival and for functional assessment of the ex vivo
      ability of the circulating radiolabeled platelets to aggregate in response to
      ADP. RESULTS: The apheresis component had a mean platelet yield of 3.2 +/- 0.4 x
      10(11) and a white cell yield ranging from 1 x 10(5) to 1 x 10(8), with a median
      of 2 x 10(7). Filtration resulted in a platelet loss of approximately 10 percent
      and a variable 2 to 3 log10 reduction in white cell content. No significant
      differences between filtered and unfiltered suspensions in paired t tests that
      would likely have an impact on platelet quality were observed in the in vitro
      tests. The in vivo recovery and survival were highly similar and not
      statistically different in filtered and unfiltered paired suspensions: the mean
      difference was 1.2 +/- 4.0 percent for recovery and 7.0 +/- 15 hours for
      survival. The functional assessment by aggregation to ADP showed no difference
      between filtered and unfiltered suspensions. A small decrease in tumor necrosis
      factor alpha and interleukin 8 was evident in the filtered suspension as compared
      to levels in the unfiltered suspensions. CONCLUSION: Prestorage white cell
      reduction in apheresis components resulted in WBC reduction by several log10 with
      no evident adverse effect on platelet viability or function.

PMID- 7825208
TI  - White cell-reduced platelet concentrates prepared by in-line filtration of
      platelet-rich plasma.
AB  - BACKGROUND: The importance of white cell (WBC) reduction in platelet concentrates
      (PCs) for component quality is undetermined. STUDY DESIGN AND METHODS: Eleven
      paired components, each derived from one of two whole-blood units given by a
      single donor on the same day, were studied. One PC was WBC reduced by filtration
      with an in-line, integral, prototype filter, and the other was produced from
      unfiltered platelet-rich plasma (PRP) by a standard method. In vitro tests
      performed on Day 1 and Day 5 were blood gases, plasma lactate, glucose, platelet
      ATP, mean platelet volume, morphology score, hypotonic stress ratio, extent of
      shape change in response to ADP, and beta-thromboglobulin. After 5 days of
      storage, each component pair was labeled with 51Cr or 111In and transfused for
      the estimation of percent recovery and survival. RESULTS: PCs using the in-line,
      prototypic filter had a platelet loss of approximately 15 percent and a variable
      1 to 3 log10 reduction (average, 95%) in WBC content. The variation in filter WBC
      removal was related to PRP WBC content and indicated that the filter did not have
      the capacity for a 3 to 4 log10 removal when PRP WBC content exceeded 1 x 10(8).
      The in vitro and in vivo measures of platelet quality showed no meaningful
      differences between filtered and unfiltered PCs by paired t test. The mean
      differences in posttransfusion percent recoveries and survivals were 0.9 +/- 2.9
      percent and 4 +/- 13 hours, respectively. Additional studies were performed using
      a larger filter with improved capacity. Those studies (n = 18) showed a
      significant improvement in filtration time and platelet yield and a consistent 3
      to 4 log10 reduction in WBCs. Filtration time was 6.6 +/- 2.7 minutes, total PC
      WBCs were 9.6 +/- 4.6 x 10(4), and total PC platelets were 7.8 +/- 1.8 x 10(10)
      (mean +/- SD). CONCLUSION: Prestorage filtration of PRP and the preparation of
      filtered platelets do not result in any significant beneficial or adverse effect
      on subsequent platelet quality. With the large-capacity filter, consistent WBC
      reduction and good platelet yields are achieved.

PMID- 7825209
TI  - Construction of bacteriophage expressing mouse monoclonal Fab fragments directed
      against the human MN glycophorin blood group antigens.
AB  - BACKGROUND: The MN human blood group antigens are complex glycopeptide antigens
      at the amino terminus of glycophorin A. Many different mouse monoclonal
      antibodies to these antigens have been produced and characterized. The
      construction of combinatorial immunoglobulin libraries displaying antibody Fab
      fragments on the surface of bacteriophage (Fab-phage) represents a novel approach
      for developing monoclonal reagents, for exploring the diversity of the immune
      response to specific antigens, and for understanding the molecular basis of the
      interaction of an antibody with its antigen. However, it is necessary to
      determine whether Fab fragments displayed on bacteriophage surfaces retain
      immunologic characteristics similar to the intact antibodies. STUDY DESIGN AND
      METHODS: Fab-phage were constructed from three anti-N (AH7, N61, and N92) and two
      anti-M (425/2B and M2A1) murine hybridomas. The Fab-phage and parental hybridomas
      were compared by enzyme-linked immunosorbent assay, Western blotting, and flow
      cytometry. RESULTS: In each case, the Fab-phage and its parental hybridoma
      antibody had similar immunologic characteristics. In particular, their dependence
      on the pH of the buffer and on sialylation of the target antigen was similar.
      CONCLUSION: These results suggest that Fab-phage may provide novel reagents with
      applications in immunohematology and may be useful in the study of the immune
      response to human blood group antigens.

PMID- 7825210
TI  - Unusual kinetics of white cell clearance in transfused mice.
AB  - BACKGROUND: Donor white cells (WBCs) in blood transfusions are responsible for
      complications in recipients, including alloimmunization, graft-versus-host
      disease (GVHD), and virus transmission and reactivation. The recent use of
      sequence-specific polymerase chain reaction assays to monitor the kinetics of
      clearance of donor WBCs in transfused humans and dogs found transient
      recirculation of donor lymphocytes on Days 3 to 5 after transfusion; this
      presumably reflected an abortive GVHD reaction to major histocompatibility
      complex-incompatible recipient cells, after which donor WBCs were cleared to
      undetectable levels. STUDY DESIGN AND METHODS: This study sought to develop a
      murine model to further characterize the kinetics and major histocompatibility
      complex restriction of donor WBC clearance. A sensitive murine Y chromosome
      specific polymerase chain reaction assay was developed and applied to serial
      blood samples collected after transfusions of allogeneic blood to naive inbred,
      primed inbred, and outbred mice, as well as after transfusions of gamma-radiated
      blood to naive inbred mice. RESULTS: In inbred mice, both naive and primed to the
      allogeneic blood donor, transfused WBCs were not cleared to undetectable levels
      for more than 1 month after transfusion. Transfused outbred mice also showed
      prolonged donor WBC survival, although at lower levels than inbred mice. There
      was no evidence of GVHD in either inbred or outbred mice, and gamma radiation had
      no significant impact on donor WBC persistence. CONCLUSION: These results
      contrast with the rapid clearance of donor WBCs observed in humans and dogs. The
      immunologic basis for this discrepancy remains unclear. Caution should be
      exercised in any extrapolation to humans of conclusions drawn from results in
      transfused mice.

PMID- 7825211
TI  - Blood transfusion and septic complications after hip replacement surgery.
AB  - BACKGROUND: The purpose of this study was to address some methodologic issues
      that might help explain the disagreement between the findings of earlier reports
      on the presumed association between allogeneic blood transfusion and the
      increased postoperative infection rates seen in orthopedic surgery patients.
      STUDY DESIGN AND METHODS: A retrospective review of the incidence of
      postoperative septic complications in 367 patients from Olmsted County,
      Minnesota, who underwent 420 elective total hip arthroplasties between 1986 and
      1993, was conducted. The infection rates in the exposed patients (those who had
      perioperatively received allogeneic blood components only or allogeneic and
      autologous blood components) were compared with those in the untransfused
      patients and patients who received only autologous blood. The study had
      sufficient statistical power to detect a deleterious effect of allogeneic blood
      transfusion equal to the 2.8-fold effect observed in a recent randomized clinical
      trial of patients undergoing elective abdominal surgery. RESULTS: There was no
      association of allogeneic blood transfusion with postoperative infection (p =
      0.226). Nineteen infections occurred in 201 exposed patients (9.5%), as compared
      to 14 infections in 219 unexposed patients (6.4%). CONCLUSION: Allogeneic blood
      transfusion does not increase the incidence of post-operative septic
      complications in patients undergoing elective total hip arthroplasty, at least to
      the extent that the statistical power of this study allowed the determination.

PMID- 7825212
TI  - Applications of flow cytofluorometry to transfusion science.

PMID- 7825213
TI  - Removing the blindfold.

PMID- 7825214
TI  - How can the safety of different types of donors be compared?

PMID- 7825215
TI  - Hemoglobinemia and hemoglobinuria complicating concomitant use of a white cell
      filter and a pressure infusion device.

PMID- 7825216
TI  - Transfusion-related acute lung injury.

PMID- 7825217
TI  - The febrile platelet transfusion reaction: a cytokine shower.

PMID- 7825218
TI  - Time course of detection of viral and serologic markers preceding human
      immunodeficiency virus type 1 seroconversion: implications for screening of blood
      and tissue donors.
AB  - BACKGROUND: Almost all human immunodeficiency virus (HIV) transmission via blood
      or tissues that has occurred since anti-HIV screening was implemented in 1985 is
      traceable to blood given after infection but before antibody seroconversion, a
      time that is referred to as the window period. In this study, the performance of
      newer assays designed to detect viral and serologic markers soon after infection
      is assessed, and the reduction in the window period achieved by these assays is
      estimated. STUDY DESIGN AND METHODS: Three cohort studies of persons at high risk
      for acquiring HIV infection were identified. These studies included well
      controlled HIV type 1 (HIV-1) polymerase chain reaction (PCR) analyses of serial
      preseroconversion specimens from HIV-1-seroconverting homosexual men or
      intravenous drug users. Of 81 enrollees with anti-HIV-1 seroconversion documented
      by a viral lysate anti-HIV-1 enzyme immunosorbent assay (EIA) available in 1989,
      13 (16%) had PCR-positive preseroconversion specimens. In the present study, sera
      from these 13 PCR-positive samples were further tested for anti-HIV by 10
      contemporary EIAs and 6 supplemental assays, as well as being tested for plasma
      p24 antigen and HIV-1 RNA. Preseroconversion sera from 38 HIV-1 DNA PCR-negative
      cohort participants were also tested by selected anti-HIV EIAs and tested for p24
      antigen and HIV-1 RNA. On the basis of these laboratory data and the intervals
      between blood drawing in all 81 men, the reduction in the preseroconversion
      window period achieved by these new assays was estimated with a mathematical
      model developed to analyze seroconversion data. RESULTS: Nine (69%) of the 13
      preseroconversion PCR-positive samples had anti-HIV that was detectable by one or
      more contemporary anti-HIV-1 or anti-HIV type 2 EIA. Supplemental antibody assays
      were negative on all four EIA-nonreactive preseroconversion samples and negative
      or indeterminate on a high proportion of the nine EIA-reactive PCR-positive
      samples. Eight (61%) of the 13 samples were p24 antigen-positive, and 11 (85%)
      were HIV-1 RNA-positive. The estimated reductions in the window period (relative
      to the index viral lysate-based anti-HIV EIA) were as follows: contemporary anti
      HIV-1/2 EIAs, 20.3 days (95% Cl, 8.0-32.5); p24 antigen and DNA PCR, 26.4 days
      (95% Cl, 12.6-38.7); and RNA PCR, 31.0 days (95% Cl, 16.7-45.3). CONCLUSION:
      Recent improvement in the sensitivity of anti-HIV assays has resulted in
      significant shortening of the preseroconversion window period. Consequently, the
      incremental reduction in the window period that could be achieved by implementing
      direct virus-detection assays has diminished significantly.

PMID- 7825220
TI  - Proceedings of the IIIrd CEC/STD meeting on schistosomiasis research.
      Noordwijk/Leiden, The Netherlands, 6-10 September 1993.

PMID- 7825219
TI  - Long-term follow-up of blood donors with indeterminate human immunodeficiency
      virus type 1 results on Western blot.
AB  - BACKGROUND: At present, tens of thousands of United States blood donors who are
      at low risk for human immunodeficiency virus type 1 (HIV-1) infection are
      indefinitely deferred. These persons are repeatably reactive for HIV-1 antibody
      in enzyme immunoassay (EIA) and are indeterminate in Western blot. STUDY DESIGN
      AND METHODS: To determine the significance and persistence of anti-HIV-1
      reactivity in plasma from volunteer blood donors with HIV-1-indeterminate Western
      blots, 66 donors were retested for HIV-1 antibody by the same manufacturers' EIA
      and Western blot 5 to 7 years after the initial Western blot. In addition,
      donors' peripheral blood mononuclear cells were tested by polymerase chain
      reaction (PCR) for HIV-1 DNA gag sequences. RESULTS: Thirty-five (53%) of 66
      donors were still repeatedly reactive for HIV-1 on EIA and indeterminate on
      Western blot, 23 (35%) were negative on EIA and indeterminate on Western blot, 7
      (11%) were negative in EIA and Western blot, and 1 (2%) was repeatedly reactive
      on EIA and negative on Western blot. Donors with persistently indeterminate
      Western blots had a band pattern nearly identical to that on the original Western
      blot. No donor was positive in Western blot, p24 antigen, or PCR testing. No
      donor had signs or symptoms of HIV-1 infection. CONCLUSION: Long-term follow-up
      of Western blot-indeterminate blood donors does not reveal evidence of HIV
      infection. A mechanism to return these donors to the donor pool should be
      considered.

PMID- 7825221
TI  - Schistosomiasis at the North Sea.

PMID- 7825222
TI  - Immunity and morbidity in human schistosomiasis mansoni.
AB  - This paper reviews the results of a longitudinal, multidisciplinary study on
      schistosomiasis mansoni that has been in progress in Machakos District, Kenya,
      since 1980. Different methods of delivering chemotherapy have been compared in a
      medium scale operational control programme. It is concluded that treatment only
      of infected children is an effective and feasible means of control, the frequency
      of treatment depending on the severity of disease. Within the framework of this
      programme, detailed studies have been undertaken of immunity to reinfection after
      treatment and of the reasons for differences in observed morbidity between
      different areas. An apparent resistance to reinfection, especially in older
      individuals, may be attributable to the protective effect of IgE antibodies
      against adult worm antigens. Various factors other than intensity of infection
      may contribute to severe morbidity, including parasite strain differences,
      interactions with other infections, nutritional status, and abnormalities in the
      regulation of pathogenic immune responses to egg antigens.

PMID- 7825223
TI  - Epidemiology, immunology and chemotherapy of Schistosoma mansoni infections in a
      recently exposed community in Senegal.
AB  - Schistosoma mansoni was introduced in the Richard Toll area (Senegal) around
      1988, probably due to man-made ecological changes in the Senegal river basin.
      Since 1991, we investigate the community of Ndombo, close to Richard Toll. Four
      random population samples of approximately 400 subjects are surveyed, starting at
      8 months intervals. Each cohort is examined parasitologically (Kato-Katz),
      clinically, serologically (circulating antigen and antibody profiles); treated
      with praziquantel 40 mg/kg; and followed up 6-12 weeks, 1 and 2 years after
      treatment. Water contact patterns and snail densities are longitudinally
      surveyed. In the first cohort, prevalence of infection was 91%, with 41%
      excreting over 1000 eggs per gram (epg); the mean egg count was 646 epg,
      individual counts up to 24,000 epg. Prevalences remained almost 100%, but egg
      counts declined strongly in adults, in spite of continued exposure and the
      supposed lack of acquired immunity. Antigen detection in serum and urine
      confirmed that the egg counts genuinely reflect variations of worm burdens. Serum
      circulating anodic antigen (CAA) provided intriguing epidemiological information
      on worm burdens, while circulating cathodic antigen (CCA) showed promise for non
      invasive diagnosis and screening. So far, similar epidemiological results were
      found in subsequent cohorts, although some variations were observed, possibly due
      to seasonal transmission fluctuations. IgE levels increased with age, while IgG4
      peaked in the age-group 10-19 years. IgE and IgG4-levels against adult worm
      antigen (AWA) and soluble egg antigen (SEA) increased between cohort 1 and cohort
      3 in almost all age-groups. In all 3 cohorts examined so far a strong correlation
      between IgG4 and pre-treatment egg-load was observed. Further follow-up and
      analysis, and comparison with chronically infected populations will provide
      insight in the development of acquired immunity. Abdominal discomfort was
      reported by 61% and diarrhoea by 33% of the subjects in the first cohort; mild
      hepatomegaly was found in 16%, splenomegaly in 0.5%. There was no correlation
      between frequency of symptoms and egg counts. This low morbidity, in spite of
      intense infections, was confirmed by ultrasound, and may be due to the recent
      nature of the focus. In the first cohort, 82% of treated subjects still excreted
      eggs 12 weeks after treatment, though egg counts declined strongly. Antigen
      detection confirmed these results. Parasitological negativation rates in
      subsequent cohorts, followed up sooner after treatment, improved but remained
      remarkably low. The low drug efficacy may be due to very rapid reinfection
      (though further reinfection after one year was limited), and/or to the lack of
      immunity in the population. Reduced susceptibility of the local schistosome
      strain can not be excluded, however. Praziquantel treatment provoked impressive
      but transient side effects (colics, vomiting, urticaria, oedema), the frequency
      of which correlated with intensity of infection.

PMID- 7825224
TI  - Studies on transmission and schistosome interactions in Senegal, Mali and Zambia.
AB  - The transmission and interaction of schistosomes in the Senegal River Basin in
      Mali and Zambia are reviewed and some preliminary field data are presented. In
      the Senegal River Basin four species of schistosomes are prevalent: Schistosoma
      mansoni, S. haematobium, S. bovis and S. curassoni as well as the following
      potential intermediate hosts: Biomphalaria pfeifferi, Bulinus globosus, B.
      umbilicatus, B. truncatus, B. senegalensis and B. forskalii. The role of each of
      these species in the transmission of schistosomes in man and domestic stock is
      discussed. Recent ecological changes caused by the construction of dams at Diama
      and Mananatali on the Senegal River, such as reduction in salinity, more stable
      water flow, creation of irrigation canals and development and extension of rice
      culture, have contributed towards the occurrence of new outbreaks of both
      intestinal and urinary schistosomiasis in the Senegal River Basin. In Mali, the
      four main areas of high prevalence of S. haematobium are Office du Niger
      (irrigation areas), Bandiagara (small dams), Selingue (dam areas) and Baguineda
      (irrigation areas). Apart from the Office du Niger, S. mansoni infections are
      rare. Surveys were carried out in the Dogon Country (Bandiagara District) in an
      attempt to confirm the recent independent reports of the presence of S.
      intercalatum. Data based on egg morphology and Ziehl Neelsen staining of egg
      shells suggested the possible occurrence of S. haematobium x S. intercalatum
      hybrids. Potential factors affecting the focal endemicity of S. haematobium in
      Mali are discussed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7825225
TI  - The epidemiology, immunology and morbidity of Schistosoma haematobium infections
      in diverse communities in Zimbabwe. I. The study design.
AB  - Recent studies on the immunology and epidemiology of Schistosoma haematobium
      infection have led to several new hypotheses regarding the relationships between
      the transmission of infection and the development of resistance to infection and
      also the associations between particular antibody and cellular reactivities with
      resistance or susceptibility to reinfection after chemotherapy. The study will
      extend the information on the development of protective immune responses during
      Schistosoma haematobium infection by examining these responses in groups of
      children and adults from areas in which differences in the peak prevalence of
      infection have been reported. Our working hypothesis is that, in areas of intense
      transmission, resistance to infection develops sooner than in areas where
      transmission is not so intense. We will investigate whether or not this is the
      case by monitoring levels of reinfection after chemotherapy and by trying to
      relate observed resistance and susceptibility to reinfection to serological and
      cellular reactivities. Exposure to infection, cercariometry and malacological
      studies will also be completed in both areas. The possibility that resistance to
      infection is associated with T lymphocyte responses classed as Th-2 type will be
      investigated by assessing reactivities to defined antigens of S. haematobium.
      This study will generate data which will be used to develop and test mathematical
      models of the epidemiological determinants which are important in human
      schistosomiasis.

PMID- 7825226
TI  - Quantitative diagnosis of Schistosoma infections by measurement of circulating
      antigens in serum and urine.
AB  - Recent research on the detection of the schistosome circulating antigens,
      circulating anodic antigen (CAA) and circulating cathodic antigen (CCA), has
      greatly expanded the scope of applications. In the present paper aspects of assay
      development, in particular of highly sensitive assays and of field-applicable
      assays, are discussed. The progress in the use of CAA- and CCA-detection for
      diagnosis, follow-up of chemotherapy and sero-epidemiological studies is
      evaluated.

PMID- 7825227
TI  - Morbidity markers for Schistosoma haematobium infection.
AB  - A description is given of a field study design, including pretreatment and short
      and long-term posttreatment measurements, which is conducted as a case-control
      study among school children in Kaloleni District, Kenya, and Kilosa District,
      Tanzania, including 500 school children from each endemic setting. The aim of the
      study is to evaluate eosinophil cationic protein (ECP) in urine as a marker for
      Schistosoma haematobium morbidity by comparing levels of ECP in urine with S.
      haematobium egg counts in urine, level of excreted S. haematobium egg antigen in
      urine, microhaematuria and urinary tract pathology assessed by ultrasonography.
      Initial results have been promising and are now subject to an extensive
      evaluation. Strong training components and transfer of technology are included in
      the project, thus contributing to the strengthening of the research capacity of
      the collaborating African institutions. Simple non-invasive assays for ECP and
      excreted S. haematobium egg antigen could provide new tools for evaluation of
      chemotherapy effects and morbidity in urinary schistosomiasis, helping to
      understand the dynamic process of posttreatment resolution and reappearance of
      pathological changes.

PMID- 7825228
TI  - Development of a vaccine strategy against human and bovine schistosomiasis.
      Background and update.
AB  - Two specific characteristics of schistosome infection are of primordial
      importance to the development of a vaccine: schistosomes do not multiply within
      the tissues of their definitive hosts (unlike protozoan parasites) and a partial
      non-sterilizing immunity can have a marked effect on the incidence of pathology
      and on disease transmission. Since viable eggs are the cause of disease
      pathology, a reduction in worm fecundity whether or not accompanied by a
      reduction in parasite burden is a sufficient goal for vaccine induced immunity.
      We originally showed that IgE antibodies played in experimental models a pivotal
      role for the development of protective immunity. These laboratory findings have
      now been confirmed in human populations. Following the molecular cloning and
      expression of a 28 kDa protein of Schistosoma mansoni and its identification as a
      glutathione-S-transferase, immunization experiments have been undertaken in
      several animal species (rats, mice, baboons). Together with a significant
      reduction in parasite burden, vaccination with Sm28 GST was recently shown to
      reduce significantly parasite fecundity and egg viability leading to a decrease
      in liver pathology. Whereas IgE antibodies were shown to be correlated with
      protection against infection, IgA antibodies have been identified as one of the
      factors affecting egg laying and viability. In human populations, a close
      association was found between IgA antibody production to Sm28 GST and the
      decrease of egg output. The use of appropriate monoclonal antibody probes made it
      possible to demonstrate that the inhibition of parasite fecundity following
      immunization was related to the inhibition of enzymatic activity of the
      molecule.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7825229
TI  - Cell-mediated immunity to schistosomes. Evaluation of mechanisms operating
      against lung-stage parasites which might be exploited in a vaccine.
AB  - This report describes parallel studies examining T cell and cytokine responses to
      Schistosoma mansoni in mice and man. The prevalence of IFNg production amongst
      murine (C57BL/6) T cell lines and clones, plus good DTH reactivity by IFNg
      secreting clones, highlights the predominance of the Th1 response in the
      pulmonary immunity characteristics of the murine irradiated vaccine model. In
      human studies, effects of anti-cytokine antibodies on the proliferation of PBMC
      from human patients to various soluble schistosome antigen preparations have been
      examined. Data suggest that both Th1 (against early antigens) and Th2 (against
      late antigens) responses are present. A role for IL-10 is highlighted in chronic
      intestinal, but not acute or chronic hepatosplenic patients, as a downregulator
      of responses which are associated with morbidity and are against late stage
      antigens.

PMID- 7825230
TI  - Evaluation of defined antigen vaccines against Schistosoma bovis and S. japonicum
      in bovines.
AB  - Our objective is to contribute to the development of defined antigen vaccines for
      schistosomiasis by evaluating the protective efficacy of Schistosoma bovis and S.
      japonicum antigens in their natural bovine hosts. Antigens under evaluation
      include some already identified as vaccine candidates: glutathione S-transferases
      (GSTs); KLH, which shares protective epitopes with the protective antigen GP38 of
      S. mansoni; and Sj23, the analogue of the vaccine candidate Sm23 antigen. In
      another approach, since crude freeze/thaw schistosomular antigen plus BCG(F/T
      vaccine) has proved protective against S. japonicum in bovines, as it was against
      S. mansoni in mice, we are carrying out further evaluations both of this crude
      antigen and of recombinant-derived paramyosins. In a third line of work, novel
      vaccine candidate antigens identified by screening our cDNA libraries with
      various passively protective animal sera are being evaluated in animal
      experiments. In the Sudan we have shown that vaccination of calves with either
      native S. bovis GSTs or KLH induces high levels of fecundity-suppression without
      causing a significant reduction in adult worm recoveries. Therefore, recombinant
      derived S. bovis 28kD GST is now being evaluated, as are the effects of combined
      GST/KLH vaccination. In China, sheep have been vaccinated with either S.
      japonicum GSTs, with KLH, or with the F/T vaccine, as a prelude to trials in
      bovines. As judged by adult worm recoveries, each type of vaccine induced
      significant protection, and there was also evidence, particularly with the GST
      and F/T vaccines, of fecundity-suppressive effects. As with the S. bovis/cattle
      system therefore, both GST and KLH showed protective effects against S. japonicum
      in sheep.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7825231
TI  - Schistosomiasis research and the European Community.
AB  - Schistosomiasis research within the framework of the Commission of the European
      Communities 'Science and Technology for Development' (CEC/STD) Programme is
      targeted at three specific problems: diagnosis of infection and disease; the
      dynamics of transmission, immunity, and morbidity; and the need for improved
      tools and strategies for control. Several important advances have been made over
      the past decade. Improved methods of diagnosis by detection of circulating
      antigens are in an advanced stage of development and have already undergone field
      trials in several epidemiological settings. Treatment and reinfection studies
      combined with immunological observations have allowed the elucidation of possible
      mechanisms leading to acquired resistance, and have shown that repeated
      chemotherapy with praziquantel can substantially reduce morbidity. Other projects
      have studied the epidemiological and ecological determinants of transmission,
      infection and disease in various endemic situations and also in newly
      established, epidemic foci where remarkable observations on chemotherapeutic
      responses were made. Important advances have been made towards the development of
      a vaccine. The glutathione-S-transferases of the major species of schistosomes
      have been cloned, sequenced and expressed, and their biological function studied.
      In a variety of vaccine formulations and animal systems GST has been able to
      confer protection against infection and to reduce worm fecundity. GST and a
      series of other crude and defined antigens have been evaluated with varying
      results in Schistosoma japonicum and S. bovis in cattle. Much work has yet been
      done, however. Recommendations as to possible future directions for research are
      provided.

PMID- 7825232
TI  - Inborn errors of biotin metabolism. Clinical and laboratory features of eight
      cases.
AB  - There are two genetically determined biotin-dependent disorders. The first is
      holocarboxylase synthetase (HCS) deficiency and the second biotinidase
      deficiency. HCS catalyzes the reaction in which active holocarboxylases are
      synthesized from inactive apocarboxylases. Biotin is required for this synthesis.
      Biotinidase facilitates the release and recycling of free biotin. Deficiency of
      either HCS or biotinidase is characterized by certain neurological, cutaneous and
      biochemical abnormalities. In this paper, six patients with biotinidase and two
      patients with HCS deficiency are described. Among the most common neurological
      findings were hypotonia (6/8), seizures (2/6) and optic atrophy (2/8). Dermatitis
      and conjunctivitis were present in three and four patients, respectively. All
      patients had low blood pH bicarbonate levels. Serum lactate was increased in all
      and pyruvate in six cases. Two patients with biotinidase deficiency presented
      earlier than the mean age of onset previously reported in the literature.
      Detection of eight cases during the past few years at a single metabolic unit
      indicates that biotinidase deficiency is not rare in Turkey, where the frequency
      of some other metabolic disorders has also been reported to be high. We suggest
      that biotin-dependent disorders should be considered in all infants with
      neurological symptoms, particularly those with jerks, even if other signs such as
      alopecia, seborrheic dermatitis and acidosis are not evident, regardless of the
      age of presentation.

PMID- 7825233
TI  - Brainstem auditory evoked potential, visual evoked potential and nerve conduction
      velocity and their relation with HbA1c and beta 2 microglobulin in children with
      insulin dependent diabetes mellitus.
AB  - Brain stem auditory evoked response (BAER), visual evoked response (VER) and
      nerve conduction velocities (NCV) were studied in 18 insulin-dependent diabetic
      children between the ages of 3.5 and 16 years (mean 9.0 +/- 3.2 years). The
      results were compared with those of age-matched controls. The VER latencies of
      the diabetic children in the right eye and left eye were significantly prolonged
      when compared with the control group. NCV of n. peroneus and the latency of
      sensorial n. medianus were significantly impaired when compared with the control
      group. Although the latencies of waves III, IV and V of the right ear and the
      interpeak latencies of I-III, I-V, III-V of both ears were prolonged, the
      comparison with the control group was not significant. The beta 2 microglobulin
      levels of the diabetic patients were significantly higher than those of the
      control group. There was a positive correlation between the beta 2 microglobulin
      and the BAER interpeak latencies of wave III-V in both ears (r: 0.51 p < 0.01).
      There was also a positive correlation between NCVs of n. peroneus and n. medianus
      (motor and sensorial) with beta 2 microglobulin (r: 0.52 p < 0.01) and between
      VER latencies (r: 0.52 p < 0.01) of both eyes separately. In our study the
      prolonged latencies of VER and BAER were detected in the absence of clinical
      abnormalities in visual and hearing systems.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7825234
TI  - Serum ferritin and hemoglobin levels of mothers and their newborns.
AB  - In this study, hemoglobin, serum ferritin, serum transferrin, transferrin
      saturation, serum iron and total iron-binding capacity were measured in venous
      blood taken from 52 primiparous mothers approximately one hour before delivery
      and in cord blood from their newborns after birth. The mean maternal serum
      ferritin level was 12.9 +/- 8.9 ng/ml. This value was lower than that of healthy
      women. The mean serum ferritin level of cord blood was 103.0 +/- 54.1 ng/ml.
      While we found no correlation between maternal and cord blood hemoglobin values,
      we observed a significant positive correlation between serum ferritin values in
      maternal and cord blood. Only the serum ferritin levels of mothers whose iron
      stores had been depleted were significantly reflected in their babies' levels (p
      < 0.001). There was no statistically significant difference in other parameters
      (p > 0.05). It is concluded that serum ferritin levels, which are affected
      earlier than hemoglobin levels, should be measured for the diagnosis of occult
      iron deficiency.

PMID- 7825235
TI  - Mesenteric and omental cysts in children. Analysis of nineteen cases.
AB  - Mesenteric and omental cysts are infrequently encountered, benign, intraabdominal
      tumors. Nineteen new patients were analysed. The most common presenting symptoms
      were abdominal distension (74%) and abdominal pain (63%). A palpable abdominal
      mass was found in 58 percent of cases. A correct preoperative diagnosis was
      established in 91 percent of the patients who were examined by abdominal
      ultrasonography. Of 19 cases documented at laparotomy, 14 patients (74%) had
      mesenteric, and five patients (26%) omental cysts. Eleven of the former were
      located in the small bowel mesentery. All of the cysts were completely removed,
      and in eight of them bowel resection was required. Subtotal gastrectomy was
      performed in one case. The mortality rate was 0%. After a mean follow-up period
      of five years, no recurrence was observed. Our study showed that abdominal
      ultrasonography by experienced professionals is the most reliable diagnostic tool
      for detecting these lesions.

PMID- 7825236
TI  - Psychosocial considerations in the management of late-diagnosed male
      pseudohermaphroditism.
AB  - Male pseudohermaphroditism (MPH), which causes ambiguous genitalia, rarely
      presents during adolescence. Herein we report two siblings diagnosed with MPH at
      the ages of 16 and 12 years and raised unambiguously as girls. Individuals with
      MPH provide caregivers the opportunity to observe the complex interaction between
      the biologic and psychosocial forces which shape gender identity. Factors which
      contribute to gender identity and the management of sex assignment may differ
      between cultures with regard to dominating sociocultural attitudes towards
      masculinity and femininity in a given society. The decision to perform feminizing
      surgery on both patients was made in consideration of these issues.

PMID- 7825237
TI  - Noncardiogenic pulmonary edema in childhood.
AB  - Pulmonary edema is caused by transudation of fluid from pulmonary capillaries
      into the alveolar spaces and the bronchiolus. It is most frequently secondary to
      either increased pulmonary capillary hydrostatic pressure (cardiogenic pulmonary
      edema) or increased pulmonary capillary permeability (noncardiogenic pulmonary
      edema). Numerous systemic and pulmonary insults are capable of damaging the
      capillary endothelium and/or alveolar epithelium, resulting in noncardiogenic
      pulmonary edema. Although clinically similar, the presence of noncardiogenic
      pulmonary edema requires a different therapeutic approach from that of
      cardiogenic pulmonary edema.

PMID- 7825238
TI  - Kidney pathology in a patient with severe combined immunodeficiency disease.
AB  - A 2-month-old SCID patient with mesangial sclerosis of the kidney is presented.
      Although the ADA status of the patient is unknown, the parents' RBC-ADA levels
      seemed to be in the heterozygote range.

PMID- 7825239
TI  - Cranial computed tomographic findings in a patient with hypertensive
      encephalopathy in acute poststreptococcal glomerulonephritis.
AB  - A 13-year-old girl with a severe headache, blurred vision, altered mental status,
      seizures, high blood pressure, edema and hematuria is presented. With a previous
      history of upper respiratory tract infection, acute onset of edema, gross
      hematuria, high ASO and low C3 levels, she was diagnosed with acute
      poststreptococcal glomerulonephritis (APSGN) and hypertensive encephalopathy.
      Computed tomography (CT) revealed symmetric hypodense areas representing edema in
      the parieto-occipital regions. As noted in previous reports, these CT findings
      are of value in establishing the diagnosis of hypertensive encephalopathy. In
      this particular case the CT appearance and the subsequent clinical improvement
      without any neurological deficit supported the diagnosis of hypertensive
      encephalopathy due to APSGN. We emphasize that awareness of the CT findings of
      hypertensive encephalopathy may facilitate in making the correct diagnosis in
      symptomatic hypertensive patients, especially in cases with an unusual
      presentation or clinical course.

PMID- 7825240
TI  - Whistling face (Freeman-Sheldon) syndrome in two siblings.
AB  - Two siblings with typical manifestations of whistling face (Freeman-Sheldon)
      syndrome (WFS) born to unaffected parents are presented. In Case 1, deep-set
      eyes, epicanthus, blepharophimosis, right lid ptosis, strabismus, anti mongoloid
      slant, small mouth, mask-like face, high-arched palate, nasal speech, dysphagia,
      kyphosis and minimal scoliosis were noted, while Case 2 displayed
      blepharophimosis, mask-like face, long philtrum, high-arched palate, scoliosis,
      bilateral post-axial polydactyly of the feet and pes varus. We corrected the
      blepharophimosis in Case 1 by bilateral canthotomy and canthoplasty. This
      syndrome is usually inherited as an autosomal dominant trait; however, some
      authors have reported an autosomal an autosomal recessive form of this syndrome
      similar to our cases. Nevertheless, this could be explained by genetic expression
      of the mutant gene.

PMID- 7825241
TI  - Total correction for tetralogy of Fallot after Brock-type operation.
AB  - We present a case of tetralogy of Fallot who had previously undergone a graded
      Brock-type operation. The post-operative development of pulmonary arteries and
      pulmonary trunk after the Brock operation were very suitable for total
      correction, which was then performed successfully. In contrast to shunt, in Brock
      type operations enlargement of the outflow tract induces symmetrical growth of
      hypoplastic pulmonary arteries without the risk of acquired pulmonary obstruction
      or peripheral stenosis at the site of anastomosis. After palliative operations,
      the repair can be deferred until the pulmonary arteries are of a suitable size.

PMID- 7825242
TI  - Plasma exchange in refractory autoimmune anemia in a child with systemic
      vasculitis associated with homozygote beta thalassemia.
AB  - A four-year-old girl presenting with fever and purpuric lesions was diagnosed
      with systemic vasculitis based on her clinical and laboratory findings. She also
      had homozygote beta thalassemia. Oral steroids were administered and during the
      course of her treatment she developed necrotizing lesions on her extremities
      along with severe myalgia and an autoimmune refractory anemia. Autoantibodies
      against the Rh antigen causing a persistent hemolysis of her erythrocytes were
      detected in her serum. Since no improvement in her skin lesions and autoimmune
      hemolytic anemia was achieved with bolus methylprednisolone therapy and
      cyclophosphamide, plasma exchange was performed. After three sessions of plasma
      exchange, her immune complex and autoantibody levels gradually declined and a
      remission in her clinical and laboratory findings was achieved. We suggest the
      use of plasma exchange along with conventional therapy for similar cases with
      ongoing immunologic injury.

PMID- 7825243
TI  - Invasive pulmonary aspergillosis in chronic granulomatous disease: response to
      systemic prednisolone treatment and locally applied amphotericin B.
AB  - A five-year-old boy with deforming and destructive invasion of pulmonary
      aspergillosis to the thoracic cage was diagnosed as having chronic granulomatous
      disease. Conventional antifungal therapy failed in this patient. Prednisolone
      therapy was added and rapidly improved the general condition of patient but
      deterioration had already been very rapid. The failure of systemic therapy
      prompted us to give amphotericin B locally to the granulomatous lesions through
      the bronchocutaneous fistula. This application yielded a good clinical response
      with closure of fistula. Despite this improvement the patient died from
      septicemia. We believe that systemic prednisolone treatment is useless in such
      cases, but local application of amphotericin B into the granulomatous lesions
      together with systemic therapy during the earlier stages of infection can
      contribute to a change in prognosis.

PMID- 7825244
TI  - Hypoglossia-hypodactylia (Hanhart's) syndrome with sensorineural hearing loss.
AB  - Hanhart's syndrome, an uncommon disorder characterized by severe micrognathia,
      hypoglossia and absence of the extremities, belongs to the oromandibular-limb
      hypogenesis group of diseases. Our patient was admitted with the complaints of
      abnormality of the mouth and absence of the upper extremities. Physical
      examination revealed severe micrognathia, a small tongue adhered to the base of
      the mouth, absence of bone, muscle and skin tissue at the lower edge of the right
      humerus and at the middle zone of the left ulna and radius. According to these
      findings, the diagnosis of hypoglossia-hypodactylia (Hanhart's) syndrome was
      made. At the age of 1 1/2 years, tympanometric examination revealed conductive
      hearing loss due to dysfunction of the eustachian tube. Auditory brainstem
      responses also revealed bilateral severe sensorineural hearing loss. A literature
      search revealed two cases of Hanhart's syndrome with conductive hearing loss, but
      no report of sensorineural hearing loss as part of this entity. Therefore, we
      present this case of Hanhart's syndrome with severe sensorineural hearing loss.

PMID- 7825245
TI  - An alternative method for pericardial patch closure.

PMID- 7825246
TI  - [Chemotherapy of breast cancer: survival and quality of life].

PMID- 7825247
TI  - [Adjuvant systemic treatment of primary breast cancer].
AB  - Systemic adjuvant therapy has improved the prognosis of patients with primary
      breast cancer. Meta-analyses have demonstrated that approximately 1/4 of deaths
      can be avoided among younger women treated with multiple cytotoxic drug regimens
      and among older women treated with tamoxifen. However, with the treatments
      available today many aspects related to the optimal therapy, taking into account
      the physical, psychological and socio-economic consequences are still open. This
      review discusses some of the major open questions related to the effectiveness of
      the adjuvant systemic therapy in terms of its ability to reduce recurrence rate
      and mortality.

PMID- 7825248
TI  - [The significance of chemotherapy for survival after recurrent breast cancer. A
      population based study of patients treated in the 1950's, 1960's and 1970's].
AB  - In a population-based study survival after recurrence was compared in three
      cohorts of patients each with a primary diagnosis of breast cancer in either
      1959, 1969 end 1979. The use of chemotherapy after recurrence in these cohorts
      was either none, sporadic or widespread. This allowed a retrospective analysis of
      the survival impact of chemotherapy. Our data suggest that chemotherapy in
      recurrent breast cancer prolongs survival by 9.5 months in patients who survive
      more than two weeks from the start of treatment for their recurrence, given the
      basic assumption that the natural history of breast cancer and the influence of
      endocrine therapy have not changed significantly during the 20-year period
      covered by the study.

PMID- 7825249
TI  - [Improved prognosis of breast cancer].
AB  - The trend in the prognosis of female patients with breast cancer has been
      investigated by comparing Kaplan-Meier survival curves of different patient
      cohorts diagnosed during the period 1948-87. The study is based on 71,448
      patients from the Danish Cancer Registry. The cohorts were defined by age at
      diagnosis, year of diagnosis and residential area. The survival time from
      diagnosis to death nearly doubled from 1948-57 to 1978-87 with the most important
      improvement taking place after 1978. Patients diagnosed in 1948-77 in the
      Copenhagen area had a far better prognosis than patients during this period in
      the rest of the country. For patients diagnosed in 1978-87 the prognosis,
      however, reached an equal level in all parts of the country. Thus, it is
      reasonable to assume that the national programme introduced in 1977 by the Danish
      Breast Cancer Cooperative Group (DBCG) has played an important role in these
      improvements.

PMID- 7825250
TI  - [Mammographic examinations in Denmark, 1990-1991].
AB  - Diagnostic mammographic activity was studied in five regions in Denmark in 1990
      1991. During this period there was only one organized mammography screening
      programme which started in the Copenhagen municipality on 1 April 1991. It is
      estimated that 49,000 diagnostic mammographic examinations were made in Denmark
      per year in the period 1990-1991. Almost two-thirds of these mammograms were
      taken in women below 50 years of age. It is important to monitor the diagnostic
      mammographic activity to ensure that this does not gradually develop into a
      screening activity. This is in particular important for women below 50 years for
      whom screening is not recommended.

PMID- 7825251
TI  - [Infrarenal aortic aneurysm. 1. Etiology and biomechanics].
AB  - The etiology of infrarenal, "nonspecific" aortic aneurysms was previously
      believed to be degenerative arteriosclerosis, but recent studies of the
      components of the aortic wall have shown that complicated disturbances primarily
      concerning the synthesis and degradation of elastin and collagen are major
      pathogenetic components. Non-invasive measurements of the biomechanical
      properties of the aneurysms and determinations of the directions and forces of
      local flow velocity vectors within the aneurysmatic sac have provided new
      knowledge of the abnormal physical factors that follow dilatation. Detailed
      studies on the biochemical and physiological factors will make it possible to
      identify patients at risk and provide the foundations for interventions that will
      prevent development of the disease.

PMID- 7825252
TI  - [Infrarenal aortic aneurysms. 2. Occurrence, diagnosis and treatment].
AB  - Infrarenal aortic aneurysms exhibit multifactorial inheritance with massive
      familial occurrence. Several large screening programmes have shown a general
      prevalence of about 3% in nonselected populations of patients over 60 years.
      Danish data on this point are not available, but is seems reasonable to suspect
      that 30,000-40,000 Danes have the disease. Only 450 operations for infrarenal
      aortic aneurysms are performed each year in Denmark (population 5.1 mill.). The
      current information with respect to incidence, prevalence, expansion rate,
      therapeutical strategies and results of vascular surgical reconstruction is
      reviewed.

PMID- 7825253
TI  - [Exophthalmometry and thyroid disease. The value of the Hertel measurement
      evaluated by a group of patients with thyroid diseases and a control group].
AB  - Exophthalmometry values from routine referrals to a hospital eye clinic are
      analysed, including adult patients with and without thyroid disease. In thyroid
      disease without eye motility complaints (n = 90) the median exophthalmometry
      value was 18 mm (range 12-28 mm). Thyroid patients with eye muscle involvement
      (diplopia, n = 47) had significantly higher values (median 22 mm, range 15-31 mm)
      but did not differ significantly from a subgroup of 51 patients without thyroid
      disease, but with "big eyes" as a (presumably) physiological finding (median
      value 20 mm, range 16-25 mm). The above three categories were all excluded from
      the control group (n = 203) which had 16 mm as median value, range 11-23 mm. Mean
      values were 16.0 +/- 1.8 mm in the females and 16.5 +/- 2.3 mm in the male
      controls. A side difference in exophthalmometry value > or = 2 mm appeared in 34%
      of thyroid patients with eye muscle involvement. This appeared in only a few per
      cent in the three other groups. Due to the wide overlap between groups, the
      solitary exophthalmometry reading is of limited diagnostic value, while the
      importance of exophthalmometry is evident when following the individual patient
      with orbital disease.

PMID- 7825254
TI  - [Cerebral arteriovenous malformations. 10 years of therapeutic results].
AB  - Results of treatment of 92 supratentorial and 19 infratentorial cerebral
      arteriovenous malformations from a 10 year period are discussed. The role of
      interventional embolization is emphasized. The results seems comparable to major
      international centres. Danish incidence evaluations indicate that it will be
      possible to gain further experience and thus better results by centralizing the
      treatment of larger arteriovenous malformations.

PMID- 7825255
TI  - [Interventional neuroradiology. A presentation with preliminary results].
AB  - During two periods (1.1.1981-3.1.1985 and 1.1.1988-31.12.1992) 57 patients were
      treated or attempted treated with endovascular embolization. The patients
      suffered either from arteriovenous malformations (AVM), dural arteriovenous
      malformations (DAVM), carotico-cavernous fistulas (CCF), giant aneurysms or
      meningenomas. During the first period the balloon-technique was mainly employed
      and only one isobutyl-2-cyanoacrylate (IBCA) embolization was carried out. Six
      AVMs and 11 CCFs were treated, and the complication rate was 33%. During the
      second period histoacryl/N-butyl-cyanoacrylate (NBCA) embolization was the
      treatment of choice for AVM and DAVM, and the balloon technique reserved for CCF
      and test occlusions. The complication rate was 8%. In 83% of the AVMs occlusion
      of more than 50% of the nidus was achieved. Three of five CCFs were occluded with
      one occluded internal carotid artery. There were no complications in test
      occlusions. Two DAVMs were reduced in size and the symptoms reduced. The patient
      material during this period consisted of 19 AVMs, two DAVMs, five CCFs, nine
      giant aneurysms (test occlusion) and five basal meningenomas with involvement of
      the internal carotid artery (test occlusion). The treatment of these relatively
      rare patients consists of close cooperation between the interventional
      neuroradiologist and the neurosurgical team.

PMID- 7825257
TI  - [Eye injuries during paintball games. The first Danish case with a summary of
      foreign experiences].
AB  - Paintball shooting is played with increasing frequency in Denmark, and ocular
      injuries can cause serious damage. The first Danish case is presented and the
      literature is reviewed.

PMID- 7825256
TI  - [Chemotherapy in metastasing breast cancer--is it beneficial?].
AB  - Carcinoma of the breast is the most common type of cancer among women in Denmark
      (3,000 new cases a year). About half of the patients will at some time develop
      metastases. Treatment of extended disease is controversial. Public discussion has
      focused on whether it is desirable to treat these patients with chemotherapy or
      not. This case story describes four cases with long term survival (nine, ten, 14,
      19 years after debut of metastases). This underlines that it is possible within
      the existing types of treatment to achieve both extended survival and acceptable
      life quality. The doctor's dilemma is that he does not know whom treatment helps.
      We conclude that treatment should be offered to all patients. This will be of
      benefit to the whole group.

PMID- 7825258
TI  - [Reduction of cholesterol and regression of the functional changes in coronary
      atherosclerosis].

PMID- 7825259
TI  - [A forum for quality and development of the public sector].

PMID- 7825260
TI  - [A pain in the neck].

PMID- 7825261
TI  - [Presentation of thought, line of thought and serotonin changes].

PMID- 7825262
TI  - [A new antiparkinson agent. Pergolide].

PMID- 7825263
TI  - [The most frequent depressive disorders. Diagnosis, classification, symptoms and
      prognosis].
AB  - The most frequent depressive disorders--anxiety and panic syndrome, dysthymic
      (neurotic) illnesses and reactive depressive adjustment disorders--were
      classified according to the new international codes. It was also explained that
      theoretical aetiological assessment principles had to be replaced by duration and
      symptomatology as operational criteria. Further, a table was elaborated for
      diagnosing depressive syndromes from an intrapsychic, social and somatic
      standpoint. Epidemiological aspects of both German and international studies were
      discussed and prognostic factors highlighted.

PMID- 7825264
TI  - [Malignant melanoma in life insurance--thickness or anatomic layer?].
AB  - The incidence of malignant melanoma has tripled during the last 40 years and
      continues to increase. Among clinical criteria the single and most significant
      prognostic factor is the extent of tumor invasion expressed by thickness rather
      than anatomical structure. Patients with melanoma thinner than 0.76 mm have a
      five year survival of 96%. Thicker tumors bear a poor prognosis. Patients having
      survived 10 years have a life expectancy close to the normal population.

PMID- 7825265
TI  - [Prognostic factors in breast cancer].
AB  - The primary aim of current research into carcinoma of the breast is, through an
      improved knowledge of tumour biology, to achieve prognostic criteria which will
      enable the more specific application of existing forms of therapy. The
      determination of newer "prognosis factors" and their "differential-diagnostic"
      value, above all in the case of patients suffering from nodal-negative carcinoma
      of the breast, serves this aim. At present, this development is in full flow.
      Final results are not yet available, but they are expected in a few years.
      Nevertheless, the concept of prognosis differentiation by means of numerous
      parameters of tumour biology represents a promising approach to a more specific
      treatment of carcinoma of the breast.

PMID- 7825266
TI  - [Viral hepatitis. Insurance medicine observations].
AB  - The major cause of liver diseases world-wide are the infectious hepatitis A-E
      which are due for different viruses. Most of the cases are clinically
      asymptomatic and without jaundice with a high rate of cure. The diagnosis and the
      differentiation of the various clinical syndromes are based mainly on serological
      markers of the involved antigen-antibody-systems. For insurance purposes the
      chronic hepatitis B, C and D are of great importance. Where chronic persistent
      hepatitis has a nearly normal life expectancy, chronic active hepatitis which may
      develop into cirrhosis and/or hepatocellular carcinoma has an increased
      mortality.

PMID- 7825267
TI  - [A panorama of rheumatic diseases].
AB  - The developments in our health care system mean that the significance of chronic,
      cost-intensive diseases is continually increasing in terms of diagnosis,
      treatment and prevention. Under this aspect, rheumatic diseases may be regarded
      as prime examples in that they generate expenditure in many areas of both social
      insurance and private insurance. Although many of the disorders classified as
      rheumatic diseases manifest themselves clinically in the form of complaints in
      the region of the skeletal system, it should not be forgotten that they are
      actually systemic disorders, i.e. they have immunological or metabolic causes.
      This aspect plays a significant role with regard to the possibility of long-term
      prognosis and hence with regard to life expectancy as well. It also exerts a
      major influence on the selection of therapeutic concepts which are hoped to slow
      down the progress of a disease or stop it altogether. Precise inquiries, careful
      diagnosis, patient-specific therapy, and not least growing health consciousness
      should be capable of exerting a positive influence on the course of even
      relatively severe rheumatic conditions. The consequences will be felt to a
      corresponding degree by the private insurers too.

PMID- 7825268
TI  - [Evaluation and underwriting overweight using the body mass index].
AB  - The BMI system meets in an ideal way all requirements in the underwriting of over
      or underweight. It is easy to handle, widely applicable and accurate. Its
      validity has been proved by several studies. Furthermore, it is the leading
      system for the evaluation of weight in all epidemiological studies. By using the
      BMI System, the advantages of clinical studies dealing with the prognosis of
      overweight can be easily introduced to the field of insurance medicine. In wide
      ranges, the mortality rates given by the BMI system match those of existing
      guidelines. On the other hand, the more favourable rating for women and older
      aged people leads to substantial advantages. The extramortality rates introduced
      by this article can be readily incorporated into automatical rating systems.
      Thereby, a risk assessment on the preselection level is made possible. By taking
      cardiovascular risk factors into proportional consideration while assessing the
      extramortality of overweight, it is possible to increase the accuracy and speed
      of the underwriting process.

PMID- 7825269
TI  - [Evaluation of hyperbilirubinemia in insurance examinations. Diagnosis of
      Meulengracht disease].

PMID- 7825270
TI  - An analysis of the causes of piglet mortality in a breeding herd kept outdoors.
AB  - The 229 piglets which died on an outdoor unit during a period of eight months
      were examined post mortem to determine the cause of death. The majority of the
      deaths (72 per cent) had occurred by the time that the litter was first inspected
      and of these 27 per cent had uninflated lungs and 53 per cent of the piglets born
      alive had no food in the stomach. Seventeen per cent of the stillborn pigs were
      of type I and 83 per cent were of type II. It was impossible to identify
      stillborn piglets reliably from their external appearance alone. At all ages,
      crushing was the most common cause of death (72 per cent of liveborn piglets).
      Six per cent of the corpses of the piglets had been damaged by birds, and attacks
      on live piglets occurred in the later stages of the study.

PMID- 7825271
TI  - Thrombocytopenic purpura in lambs given bovine colostrum.
AB  - Newborn lambs which had been given colostrum from a single cow developed
      thrombocytopenia and seven died. The clinical signs included purpura,
      haemoglobinuria, melaena, dullness and lethargy. The lambs died at one to two
      days old. Post mortem examination revealed widespread haemorrhages throughout the
      body. Lambs given small amounts of colostrum developed a transient
      thrombocytopenia but did not die.

PMID- 7825273
TI  - Bovine disseminated haemangioma.

PMID- 7825272
TI  - Adverse reactions in cattle to a capripox vaccine.
AB  - Capripox vaccine (strain 0240) caused severe generalised skin reactions in
      vaccinated dairy cattle in two herds, whereas beef cattle did not develop
      reactions. All the reacting animals developed lumpy skin disease-like lesions.
      The incidence of skin lesions in first-lactation cows in herd A was 22.9 per cent
      and in herd B 29.3 per cent, mainly in the post-calving period. In older cows,
      the incidence was 10 per cent in herd A and 12.4 per cent in herd B. In herd B
      the high-yielding lactating cows were the most severely affected. There was a
      decrease of 3.5 per cent in milk production in each herd over a period of 12
      days, and six first calving animals (3.5 per cent) and six cows (1.5 per cent)
      were slaughtered. A capripox virus was isolated from the animals with severe
      lesions, and was also demonstrated by electron microscopy. The histopathological
      lesions were similar to those of lumpy skin disease. The extent of the lesions
      appeared to be stress-related and, to a lesser degree, correlated with age and
      breed.

PMID- 7825274
TI  - Prevalence and possible causes of subcapsular liver rupture in dead, newborn
      lambs.

PMID- 7825275
TI  - Piglet serology: a method of monitoring herd Aujeszky's disease status.

PMID- 7825277
TI  - Suspected transmission of leishmaniasis.

PMID- 7825276
TI  - Strengthening links in eastern Europe.

PMID- 7825278
TI  - [Peacetime military hospitals at the beginning of World War II].

PMID- 7825280
TI  - [The tasks for the automated management of the actions of an emergency medical
      service under extreme conditions].

PMID- 7825281
TI  - [The creation of regional centers for the training of specialists in disaster
      medicine].

PMID- 7825279
TI  - [Experience in organizing medical care for the servicemen of the Baku garrison
      during the armed conflict of 1990].
AB  - The article gives a brief description of tactical and medical situation of Baku
      garrison during military conflict, and also the data concerning the character and
      the structure of sanitary losses, and the volume of medical care. Organizational,
      transportation, personnel and logistic problems of medical support of troops are
      also described. The proposals are given how it is possible to settle these
      problems in the preparatory period.

PMID- 7825282
TI  - [Pressing problems in the diagnosis and surgical treatment of knee joint
      pathology in servicemen].

PMID- 7825283
TI  - [The use of electrochemically activated solutions for treating burn wounds].

PMID- 7825284
TI  - [The clinical morphology of cardiac involvement in typhoid in servicemen in
      Afghanistan].
AB  - The article is based on the results of studies of protocols of 65 autopsies, 42
      medical histories and morphological studies of contemporary records of 47 hearts
      of the deceased servicemen from the Soviet troops in Afghanistan who died of
      typhoid. It was found out that myocarditis was developed in 61.9 7.3% of cases
      regardless of the existence and character of complications. The inalienable
      features of myocarditis were inflammatory changes (vasculitis, basically
      mononuclear infiltration of stroma, granulomas), vascular malfunctions
      (microcirculatory disorders, enhanced permeability of vessels, edema of stroma),
      dystrophic and necrotic changes in cardiomyocytes. Vasculitis had predominant
      significance in cardiac morphogenesis. Besides myocardium the inflammatory
      process had proliferated also on epicardium and mural endocardium, i.e.
      pancarditis.

PMID- 7825285
TI  - [A priceless contribution to the theory and practice of military public health].
AB  - The article is dedicated to the outstanding figure in national medicine--colonel
      general MD E.I. Smirnov (1904-1989), the Hero of Socialist Labour, member of the
      Academy of Medical Sciences of the USSR, who was the Head of the Main Military
      Sanitary Department of the Red Army during the Great Patriotic war, and the
      Minister of Health of the USSR in the post-war period. The main attention of the
      author is drawn on the contribution of E.I. Smirnov to the development of
      military medicine. The article makes a detailed analysis of the role of E.
      Smirnov in the development and practical implementation of military medical
      doctrine and the antiepidemic support system during the years of the Great
      Patriotic War, as well as his contribution for organizational arrangement of
      field therapy as an independent scientific discipline and as a subject of study
      in the system of medical education; his merits in organization of specialized
      medical care; formation of an institution of senior medical specialists; reforms
      in military medical education. The article contains many concrete examples which
      characterize a celebrated personality of E.I. Smirnov and his leadership
      qualities.

PMID- 7825286
TI  - [The cryovacuum surgery of tumors of the facial skin and oral mucosa].

PMID- 7825287
TI  - [Radiation-induced cataracts from local overexposure of the eyes].

PMID- 7825288
TI  - [Organ-preserving operations in the early stages of breast cancer (a review of
      the literature)].

PMID- 7825289
TI  - [The pharmacological correction of immune homeostatic disorders in servicemen].

PMID- 7825290
TI  - [The psychophysiological characteristics and correction of extreme states of an
      informational-semantic origin].
AB  - The article deals with the general characteristics of extreme states influence.
      The authors systematize the factors which may be considered as extreme ones. The
      article shows that the development of different extreme states frequently is
      predetermined by informative-semantic nature. The following types of extreme
      states of informative-semantic genesis were studied: emotional tension, anxiety,
      fear, affective excitement, inhibition, depersonalization. There are
      psychophysiological characteristics of these states and basic methods of its
      correction.

PMID- 7825291
TI  - [The hygienic diagnosis of the soil under current conditions].

PMID- 7825292
TI  - [The lipophagocytic function of the blood leukocytes in pilots].

PMID- 7825293
TI  - [A hygienic validation of prospective ways to decrease the amount of solid wastes
      on board ship].
AB  - The most perspective way of reduction of solid waste on board the ship is to
      modify the system of food supplies. The new system must provide for food which is
      completely ready for use or contain semi-finished products which need few
      cookery. The food packings must be easily utilized or recycled. The existing
      amount of garbage on board the ship will be sorted, pressed, treated by
      conservants, packed into polyethylene bags, and stocked in special compartments
      or vacant refrigerated store-rooms. The realization of these proposals will make
      it possible to reduce the quantity of garbage on board the ship, lower the
      expenditure of labour and electricity for cookery, reduce the potable water
      consumption, and diminish the size and the quantity of caboose equipment. It's
      possible to use electric ovens to heat the food, reduce or exclude the usage of
      submarine disposable containers, and thus, preserve the ecology of world ocean.

PMID- 7825295
TI  - [Spontaneous tumors in domestic animals].

PMID- 7825294
TI  - [The pepsinogen-pepsin system under normal conditions and in gastric
      carcinogenesis].

PMID- 7825296
TI  - [Morbidity and mortality from colonic cancer in the population of St.
      Petersburg].

PMID- 7825297
TI  - [Ways of improving the quality of life for cancer patients].

PMID- 7825298
TI  - [Nuclear proteins of human leukocytes in health and in chronic leukemias].
AB  - The levels and fractional composition of nuclear proteins of human leukocytes
      (histones, total non-histone proteins and HMG-proteins) have been studied in
      healthy subjects and cases of leukemia. It has been shown that the levels of
      histones and total non-histone proteins in normal myeloid cells are, on the
      average, 1.5 times those in lymphoid cells. Leukemia has been shown to involve
      elevated concentrations of high-molecular components in the histone and HMG
      protein fraction of white blood cells as well as a slight decrease in both high-
      and low-molecular components in the fraction of total non-histone proteins. This
      points to disturbances in the epigenomic regulation of the genome involved in
      leukemia.

PMID- 7825299
TI  - [Changes in lipid peroxidation and phospholipid spectrum of blood in patients
      with lung cancer].
AB  - The parameters of the lipid peroxidation - antioxidants system, phospholipid
      profile, erythrocytes and blood plasma of 47 patients with lung cancer were
      studied. Serious disturbances in phospholipids profile in cases of central and
      peripheral lung cancer were identified. They included a decreased
      phosphatidycholine level, accumulation of lysophospholipids and appearance of
      phosphatidyglyceral fraction in blood plasma. Those shifts occurred alongside
      with enhanced lipid peroxidation and a deficit of antioxidation protection
      factors.

PMID- 7825300
TI  - [Clinico-experimental study of using plant preparations from the flowers of
      Filipendula ulmaria (L.) Maxim for the treatment of precancerous changes and
      prevention of uterine cervical cancer].
AB  - The paper reports the results of the experimental and clinical evaluation of the
      administration of drugs prepared from flowers of Filipendula ulmaria (L.) Maxim
      for cervical dysplasia and cancer treatment. Local administration of decoction
      resulted in a 39% drop in the frequency of squamous-cell carcinoma of the cervix
      and vagina induced in mice by 7,12-dimethyl-benz(a)anthracene treatment. Positive
      response was recorded in 32 patients (67%), including 25 cases (52%) of complete
      regression of dysplasia, out of 48 cases of cervical dysplasia treated with
      courses of ointment application. No recurrence was observed in 10 completely
      cured patients within 12 months.

PMID- 7825301
TI  - [Function-sparing surgery in the combined therapy of laryngeal cancer].
AB  - The reports deals with the principle and methods of making a two-stage diagnosis
      of laryngeal tumor evolved on the basis of the data on two calibrated groups of
      250 patients each and a computer-supported procedure of mathematical analysis.
      Two programs for a MC-52 microcalculator are suggested to select the scope of
      surgical intervention. Such procedures of preoperative radiation therapy as
      exposure under hyperbaric oxygenation conditions, cutting down the preoperative
      radiation dosage and shortening the interval between ir radiation course and
      surgery have been improved. Five improved procedures of saving therapy for tumors
      of the supraglottic area and four--for glottic cancer were used in 142 patients.
      The functional and oncological results of saving surgery were evaluated in 458
      patients receiving combined treatment for laryngeal tumors. Said results were
      found to be beneficial.

PMID- 7825302
TI  - [Effect of preventive fluorographic mass screening on the prognosis of lung
      cancer and tuberculosis].
AB  - A survey of mass X-ray examinations of the thoracic cavity carried out in
      Leningrad in 1983-1991 showed the number of screenees to drop from 3.2 to 2.1 mln
      per year within the last three years (1988-1990). This finding is matched by an
      increased number of patients with primary lung cancer, a decrease in the numbers
      of cases of radical surgical treatment and those with lung tuberculosis
      identified by X-ray, and a steady increase in tuberculosis mortality.

PMID- 7825303
TI  - [Ultrasonography in the assessment of regional lymph nodes in stomach cancer].
AB  - The echographic and histological data on regional lymph nodes in 56 cases of
      stomach cancer were evaluated. Microwave examinations offer a sensitivity of
      91.1% and a specificity of 30.4% for this localization. Although a focus of
      hyperplasia cannot be differentiated from a metastatic lesion on the basis of
      echographic evidence, enlargements of microwave examination-established patterns
      might suggest a more thorough revision of areas of regional metastases,
      intrasurgical biopsy, in situ cytologic examination and possibly an extended
      lymphadenectomy during surgery.

PMID- 7825304
TI  - [Comparative evaluation of effectiveness of some methods of treatment in locally
      invasive cancer of the urinary bladder].
AB  - Five-year survival cumulative results have been used to assess the efficacy of
      treatment for locally extended carcinoma of the urinary bladder using different
      methods: radiation + resection of bladder + chemotherapy; radiation + cystectomy
      with ureterosigmoanastomosis+chemotherapy; radiation + cystectomy with
      ureterocutaneostomy + chemotherapy; chemoradiation treatment. In the group of
      patients with tumors T2(m)NoxMo, the best cumulative results for survival (65 and
      70%) were obtained in cases of organ-saving surgery. In tumor T3a, bNox(+, -)Mo
      group, the best results for survival (31.3%) were registered in patients who had
      undergone cystectomy. Five-year survival level was not attained in patients with
      tumors T4a, bNox, IMo, which makes the case for chemoradiation treatment
      application.

PMID- 7825305
TI  - [Perspectives of providing preventive oncology screening at large industrial
      plants].
AB  - The introduction of an automated ramified system of questionnaire-based surveys
      developed at the Institute and tested at large plants and factories of the city
      has both noticeably improved the standards of cancer-control screening campaigns
      and has cut their costs. The study was concerned with evaluation of the
      effectiveness of identification of cancer pathology of two major localizations-
      gastrointestinal tract (21,779) and mammary gland (32,334).

PMID- 7825306
TI  - [Sequelae of iatrogenic occlusion of the celiac trunk in a patient with liver
      metastases].

PMID- 7825307
TI  - [Embolization of cavernous hemangioma of the liver complicated with arteriovenous
      shunt].

PMID- 7825308
TI  - [Cytologic features of sinus histiocytosis with massive lymphadenopathy (Rosai
      Dorfman disease)].

PMID- 7825309
TI  - [Primary isolated lymphoblastic lymphosarcoma of the brain].

PMID- 7825310
TI  - [Pregnancy in a patient with lymphoblastic lymphosarcoma in complete remission].

PMID- 7825311
TI  - [Classification of oncologic diseases in the new editions of the International
      Classification of Diseases].

PMID- 7825313
TI  - Almost heaven?: rural family practice in West Virginia.

PMID- 7825312
TI  - Access to medical care in West Virginia: implications for policy.
AB  - Access to medical care is an important goal of health care reform. In West
      Virginia, access to care has been defined in terms of insurance coverage and the
      availability of health care professionals, especially primary care practitioners.
      In recent years, three surveys have attempted to measure access to care. These
      surveys show that approximately 200,000 to 230,000 West Virginians needed medical
      care but were not able to obtain it because they could not afford it. A much
      larger number, about 540,000 West Virginians, put off or postponed seeking care
      they felt they needed because they could not afford it.

PMID- 7825314
TI  - Seventeen level laminectomy for extensive spinal epidural abscess: case report
      and review.
AB  - Several studies have suggested that non-operative treatment be employed for
      spinal epidural abscesses involving a considerable length of the vertebral
      column. The reasons for this have not been clearly stated in the literature,
      however, nor has the critical number of vertebral levels been specified.
      Presumably, this is related to the morbidity of extensive laminectomy, but we
      began to question this assumption because of advances in surgical instrumentation
      combined with frequent reports of irreversible disease progression while on
      appropriate antibiotics. In this article, we present a case of an extensive
      spinal epidural abscess managed surgically with no associated morbidity. In
      addition, we present a review of the literature concerning spinal epidural
      abscess.

PMID- 7825315
TI  - An overview of adulthood attention deficit hyperactivity disorder.
AB  - Attention deficit hyperactivity disorder (ADHD) in adulthood has become an
      increasingly recognized and clinically significant psychiatric syndrome. This
      article reviews the criteria for diagnosing adulthood ADHD, secondary
      complications of the disorder, and pharmacological methods for treating this
      disorder.

PMID- 7825316
TI  - A spontaneous esophageal perforation and duodenal ulcer perforation resulting in
      a subpulmonic abscess.
AB  - Both spontaneous esophageal perforations (Boerhaave syndrome) and duodenal ulcer
      perforations are medical emergencies. Spontaneous esophageal perforation (SEP) is
      the most serious and rapidly lethal perforation of the gastrointestinal tract.
      Prompt diagnosis and early therapy is needed to prevent death and prolonged
      serious illness, and the key to the diagnosis is an awareness of its frequent
      atypical presentations. This article presents a case report of SEP and duodenal
      ulcer perforation which caused a right-sided subpulmonic abscess and reviews the
      literature pertaining to this subject.

PMID- 7825317
TI  - [Pancreatic carcinoma--report of progress and prospects].

PMID- 7825318
TI  - [Pancreatic carcinoma--epidemiology and risk factors].
AB  - The incidence of pancreatic cancer has increased steadily over the past decades
      throughout the world. Pancreatic cancer is the fifth leading cause of death from
      cancer in the western world. In 1991 1074 Austrians died of pancreatic cancer.
      Over 80% of cases occur in the age group of 60-80 year olds. The incidence is
      higher in men than in women by a ratio of about 1.5 to 1. There is strong
      evidence that pancreatic cancer risk is increased with cigarette smoking,
      increasing protein intake and fat consumption and nonalcoholic chronic
      pancreatitis. A reduction in the incidence of pancreatic cancer will only be
      achieved through selected prevention programmes.

PMID- 7825319
TI  - [Pancreatic carcinoma--diagnosis and screening--endoscopic therapy].
AB  - Diagnosis of pancreatic carcinoma is nowadays established by means of
      transabdominal sonography and computed tomography. In cases remaining unclear or
      accompanied by obstructive jaundice ERCP is also required. Small tumours can only
      be detected by ERCP or endosonography with sufficient accuracy. Biopsy
      (percutaneous or ductal during ERCP) should be restricted to cases in which the
      histologic or cytologic results influence therapeutic concepts substantially.
      Magnetic resonance imaging and endoscopy of the pancreatic duct are currently
      being evaluated. Tumor markers such as CA 19-9 are mostly useful in confirming
      suspicious morphology; their specificity and the sensitivity in small tumours are
      unsatisfactory. Precise pretherapeutic staging with computed tomography,
      endosonography, and laparoscopy can avoid superfluous surgical procedures. Early
      diagnosis of pancreatic cancer appears possible at present only by means of ERCP
      or endosonography, but patients at risk still have to be defined since blind
      screening would be ineffective due to insufficient specificity, expensive and
      dangerous due to the complications of the applied methods. In the patient with
      obstructive jaundice unfit for surgery, or with metastatic spread of the disease,
      endoscopic stent insertion is the palliative treatment of choice. Because of
      longer patency metal stents are superior to plastic endoprotheses.

PMID- 7825320
TI  - [Possibilities and limits of cytostatic chemotherapy in pancreatic carcinoma].
AB  - The investigation of chemotherapy for pancreatic cancer has been hampered by the
      fact that most patients present with severe general illness and thus tolerate
      this form of treatment poorly. Furthermore, because of the relative
      inaccessibility of the pancreas it has been difficult to monitor objective
      response rates. In patients with disseminated disease only few drugs have shown
      antitumour activity and the response rates generally do not exceed 20%. Several
      combination regimens have been tested. Of those assessed in randomized trials,
      the median survival has ranged from 2 to 6.5 months, which is not significantly
      better than with supportive therapy alone. Endocrine treatment measures and
      certain experimental treatment approaches such as reversal of multidrug
      resistance, photodynamic therapy and radioimmunotherapy may represent promising
      fields for future research. Encouraging preliminary results, however, warrant
      confirmation in controlled clinical trials. In patients with unresectable though
      localized pancreatic tumours the use of conventional external-beam radiation
      therapy plus 5-fluorouracil can significantly increase survival. Combined
      radiochemotherapy also seems to play an important role in the postoperative
      adjuvant treatment of potentially curative tumours, increasing the long-term
      results of surgical management.

PMID- 7825321
TI  - [Pancreatic carcinoma--the status of extensive interventions].
AB  - The five-year survival rate after resection of carcinoma of the pancreas remains
      unsatisfactory. The R0 resection rate (histologic-radical) as well as the five
      year survival rate can be improved by extension of resection to neighbouring soft
      tissue structures, including lymphadenectomy under consideration of the
      anatomical site of the pancreas. An extension to other organs of the upper
      abdomen does not appear to have any influence on long-term survival. The choice
      of the safest reconstructive procedure influences the long-term outcome by
      decreasing post-operative mortality and morbidity.

PMID- 7825322
TI  - [Anastomotic ulcers after duodenopancreatectomy for carcinoma of the head of the
      pancreas].
AB  - Anastomotic ulceration following partial pancreatoduodenectomy carries a
      substantial risk of complications. More than 50% of patients have episodes of
      bleeding and up to 20% die as a direct consequence of peptic complications. In a
      retrospective study of 88 patients, frequency of ulcer was analysed comparing
      Whipple-Child reconstruction and partial pancreatoduodenectomy with a Roux-Y
      gastrojejunostomy. Indication was ductal carcinoma of the pancreas in 80 cases
      and periampullary carcinoma in eight patients. Roux-Y gastrojejunostomy was
      performed in 53 cases, Billroth-II anastomosis with enteroanastomosis in 35
      patients. Perioperative mortality was 7% (n = 6). Nine cases of anastomotic
      ulceration were verified after Roux-Y gastrojejunostomy (18%). Three out of five
      Roux patients with a periampullary carcinoma developed ulcers. After Billroth-II
      reconstruction anastomotic ulceration was found in only one out of 33 cases (3%).
      Six ulcers presented with bleeding, anastomotic stenosis occurred in two cases.
      Three ulcer patients with curatively resected periampullary carcinoma were
      reoperated. After resection of the Roux limb and truncal vagotomy no recurrence
      was seen during a follow-up period of 19 to 46 months. Roux-Y gastrojejunostomy
      carries an increased risk of anastomotic ulceration. The lack of inactivation of
      pepsin by bile acids has to be discussed as an underlying mechanism.

PMID- 7825323
TI  - [Therapeutic possibilities in cardiac arrhythmias].

PMID- 7825324
TI  - [Classification and mechanism of action of anti-arrhythmia drugs].
AB  - The knowledge of basic electrophysiologic functions and of ion fluxes across the
      cell membrane of excitable tissues seems essential for the understanding of the
      action mode of antiarrhythmic drugs. Therefore, the rather complex physiological
      interconnections at the membrane site are briefly reviewed. Moreover, the
      interaction mechanisms of antiarrhythmic drugs with transmembraneous ion
      movements are discussed. The classification of antiarrhythmic agents as proposed
      by Vaughan-Williams is critically discussed, emphasizing that each drug has a
      particular electrophysiologic action.

PMID- 7825325
TI  - [Therapeutic indications, principles and guidelines of differential drug therapy
      of cardiac arrhythmias].
AB  - Several arrhythmias have different causes and different needs for therapy.
      Indications for antiarrhythmic therapy is related either due to an increased
      mortality risk, predominantly if ventricular arrhythmias are present, or due to a
      decreased quality of life, especially in supraventricular arrhythmias (SVA). In
      the past decades diagnostic and therapeutic methods were improved, many new
      antiarrhythmic drugs entered the clinical use and new devices came up. In general
      the number of therapeutic strategies increased up to the confusing present stage.
      Drug therapy of SVA is furthermore based on the use of calciumantagonists, beta
      blockers and digitalis, with a smaller amount other class III and class I
      antiarrhythmic agents. Nevertheless new curative methods were developed like the
      various ablation-techniques, which gives the patient a tremendous chance to live
      without any attack and without any drug. In ventricular arrhythmias the hopes of
      a mortality reduction due to drug therapy could not be fulfilled, especially in
      the use of class I antiarrhythmic agents. They seemed to be proarrhythmogenic,
      which increases with the impairment of left ventricular function. Only class III
      antiarrhythmic drugs could reduce the increased mortality risk in specific
      populations. Consequently drug therapy in ventricular arrhythmias will be done
      cautiously under the aspects of proarrythmogenicity and the lack of convincing
      results, that the suppression-hypothesis works. Alternative therapeutic methods
      came up and should not withheld in high risk patients.

PMID- 7825326
TI  - [Differential diagnosis of tachycardic arrhythmias and its importance for
      therapeutic decisions].
AB  - The widespread application of catheter ablation techniques has significantly
      affected the meaning of non-invasive evaluation of both supraventricular and
      ventricular tachycardias. In patients with different forms of supraventricular
      tachycardias radiofrequency current ablation offers comparable high success
      rates. Therefore, since non-invasive and invasive classification of
      supraventricular tachycardias agree only in 80% of patients, the diagnosis based
      on non-invasive means may constitute a bias, but does not obviate the need for a
      scrutinized preablation electrophysiologic study to determine the very type of
      tachycardia. In contrast, in patients with ventricular tachycardias a manyfold of
      different therapies is available: antiarrhythmic drug medication, catheter
      ablation or surgical intervention including the implantation of programmable
      cardioverters/defibrillators. The selection of the optimal therapy, however, is
      predominantly dependent on the clinical presentation of tachycardia, on the type
      and the severity of the underlying structural heart disease and on the potential
      mechanism of tachycardia.

PMID- 7825327
TI  - [Differential diagnosis and therapy of bradycardic arrhythmias].
AB  - The most important symptoms in bradycardia are vertigo, dizziness and syncopy due
      to diminished cerebral blood sypply. Cardial symptoms are cardiac insufficiency
      and angina pectoris. By means of ECG, especially Holter-ECG, carotid sinus
      massage, atropin test and invasive methods (atrial stimulation, His-bundle ECG)
      sinu-nodal dysfunction, carotid sinus syndrome, bradyarrhythmia absoluta and AV
      block can be diagnosed. Pharmacological treatment is only useful in acute
      situations. For symptomatic bradyarrhythmias the implantation of a Pacemaker is
      the therapy of choice. Individual treatment of the various types of
      bradyarrhythmia and the patients special needs is possible through the evolution
      of pacemaker technology.

PMID- 7825329
TI  - [Therapy monitoring in cardiac arrhythmias: guidelines for evaluation of anti
      arrhythmia effects].
AB  - The incidence of avoidable or unavoidable, cardial and extracardial side effects
      is a risk in the drug treatment of supraventricular and ventricular
      tachyarrhythmias. Therefore the indication of antiarrhythmic drug therapy has to
      be considered critically. The patient has to be controlled close-meshed,
      especially at the beginning of the drug treatment. In patients with life
      threatening ventricular tachyarrhythmias, which can not be suppressed by drug
      therapy, nonpharmacological therapy--implantable cardioverter/defibrillator,
      catheterablation and heart-transplantation--has to be discussed.

PMID- 7825328
TI  - [Atrial fibrillation--from delirium cordis to therapeutic challenge].
AB  - Atrial fibrillation may develop in patients without (line atrial fibrillation) or
      with heart disease. Its prevalence raises with age. Medical or electrical
      cardioversion should be considered in view of the unfavourable hemodynamics and
      the increased risk of embolic events. Class-I antiarrhythmics given to sustain
      sinus rhythm after cardioversion are fraught with the risk of sudden death and
      should therefore be replaced by class-III antiarrhythmics. Control of heart rate
      in persisting atrial fibrillation is achieved best by digitalis glycosides at
      rest and by calcium channel blockers of the verapamil type or beta blockers
      during exercise. The risk of embolism in nonvalvular atrial fibrillation is
      reduced by mild oral anticoagulation and, probably to some extent, also by
      aspirin (300 mg daily). Ablation of the AV-node or an accessory pathway or heart
      surgery (maze procedure) may provide help in special cases.

PMID- 7825330
TI  - Ciphering the new alphabet: Rx for APN.

PMID- 7825331
TI  - Primary care and nurses.

PMID- 7825332
TI  - The health care burden of cigarettes on Wisconsin communities, 1994.

PMID- 7825333
TI  - CDC report on teen smoking.

PMID- 7825334
TI  - The daily burden of smoking in an average Wisconsin community.

PMID- 7825335
TI  - Attitudes of the Wisconsin State Legislature toward tobacco control policies.

PMID- 7825336
TI  - Tobacco acquisition practices of adolescents in two Wisconsin communities.
AB  - More than 2,000 students in two Wisconsin communities were surveyed on their
      tobacco use and acquisition habits. The results indicate a defined pattern of
      acquisition across the three grade levels surveyed. Eighth grade tobacco users
      buy or "bum" tobacco from friends but also use a wide variety of methods and
      sources. Tenth and 12th grade tobacco users primarily purchase tobacco from
      businesses. About one third of 8th grade tobacco users regularly buy from vending
      machines and almost half of the 8th and 10th grade tobacco users in one of the
      communities have shoplifted tobacco during the past year, with 12% most often
      obtaining tobacco in this manner. These patterns of acquisition may have a
      contributory effect on the high prevalence of adolescent tobacco use reported in
      both communities. The results argue for meaningful enforcement of laws
      prohibiting tobacco sales to minors and the elimination of self-service sales of
      tobacco products.

PMID- 7825337
TI  - Blinded by the light: the folly of tobacco possession laws against minors.

PMID- 7825339
TI  - Intraoperative two-dimensional echocardiography and color flow Doppler imaging: a
      basic transesophageal single plane patient examination sequence.
AB  - Recent advances in technology have allowed application of transesophageal
      echocardiography to intraoperative care of critically ill patients. Early
      clinical application primarily involved evaluation of left ventricular regional
      wall motion. However, valid intraoperative use of transesophageal
      echocardiography should also encompass systematic assessment of the entire heart
      as well as the great vessels. This report describes a 10-step sequence of single
      plane, two-dimensional echocardiographic views which constitute a basic patient
      examination capable of being performed by a practitioner whose primary
      responsibility is the delivery of anesthesia care. A 5-step color flow Doppler
      examination sequence is also presented. These views complement the two
      dimensional echocardiographic steps. Representations of methods for grading
      Doppler-defined valvular regurgitation complete the report.

PMID- 7825338
TI  - Myocardial ischemia--association with perioperative cardiac morbidity.
AB  - The development of ambulatory electrocardiographic recorders and analysers and
      the application of transesophageal echocardiography in the mid-1980's enabled
      investigators to quantify and describe the occurrence of silent as well as
      symptomatic ischemia in the perioperative period. Several technical advances
      which have recently occurred in ECG monitoring include the use of miniaturized
      digital computing equipment to store and analyze data. In addition, real time ST
      segment analysis has become widely available on multicomponent monitors in both
      the operating room and intensive care units. The incidence of perioperative
      myocardial ischemia depends on the patient population, the surgical procedure,
      and the monitoring technique used. Several studies in the early 1990's have shown
      that cardiac morbidity in patients undergoing major, noncardiac surgery is best
      predicted by postoperative myocardial ischemia, rather than tradition
      preoperative clinical predictors. Long duration postoperative ischemia may be the
      factor most significantly associated with adverse cardiac outcome. Postoperative
      pain, physiological and emotional stress may all combine to cause tachycardia,
      hypertension, increase in cardiac output, and fluid shifts which, in high risk
      patients, might result in subendocardial ischemia and eventual myocardial
      infarction. If postoperative myocardial ischemia is the cause of late
      postoperative myocardial infarction in patients undergoing non-cardiac surgery,
      then treatment of postoperative myocardial ischemia should reduce morbidity. In
      addition, reducing pain and stress and avoiding postoperative hypoxemia might
      prevent postoperative myocardial ischemia and minimize the need for extensive
      preoperative cardiac evaluation.

PMID- 7825340
TI  - Preoperative evaluation of the cardiac patient for noncardiac surgery.
AB  - Perioperative cardiac events continue to represent a significant cause of
      morbidity in patients undergoing noncardiac surgery. The evaluation of the high
      risk patient should begin with an assessment of the probability of coronary
      artery disease and exercise tolerance. Decisions to undergo further evaluation,
      including noninvasive testing, should be based upon the perioperative morbidity
      and mortality rate for the planned surgical procedure. In patients with
      significant coronary artery stenoses and a high probability of perioperative
      cardiac morbidity, coronary artery bypass grafting, percutaneous transluminal
      coronary angioplasty, and preoperative optimization of hemodynamics in an
      intensive care unit have all been advocated as means of reducing risk.

PMID- 7825341
TI  - Cardiac output monitoring by echocardiography: should we pass on Swan-Ganz
      catheters?
AB  - Transesophageal echocardiography offers a noninvasive technique for the
      continuous monitoring of cardiac performance. The combination of 2-dimensional
      echocardiography and Doppler velocitometry provide assessment of cardiac anatomy,
      valve function and, ventricular loading conditions. Although transesophageal
      echocardiography has become accepted for perioperative monitoring, it is
      typically used in conjunction with Swan-Ganz catheterization. To supplant Swan
      Ganz catheters, an echocardiographic technique to monitor cardiac output is
      necessary. Despite considerable effort to achieve this goal, a satisfactory
      technique has been difficult to realize. This paper discusses the role of cardiac
      output monitoring in perioperative care and critically examines echocardiographic
      techniques for cardiac output monitoring.

PMID- 7825342
TI  - Brachial plexus anesthesia: an analysis of options.
AB  - There are multiple sites at which the brachial plexus block can be induced in
      selecting regional anesthesia for upper extremity surgical patients. The most
      frequently used blocks are axillary, infraclavicular, supraclavicular, and
      interscalene. One must understand brachial plexus anatomy to use these blocks
      effectively, as well as the practical clinical differences between the blocks.
      Axillary brachial plexus block is most effective for surgical procedures distal
      to the elbow. This block is induced at a distance from both the centroneuraxis
      and the lung; thus, complications in those areas are avoided. Infraclavicular
      block is often the most effective method of maintaining a continuous block of the
      brachial plexus, since the catheter is easily secured to the anterior chest.
      Supraclavicular block provides anesthesia of the entire upper extremity in the
      most consistent, time-efficient manner of any brachial plexus technique; however,
      the block needle is necessarily positioned near the lung during injection.
      Interscalene block is especially effective for surgical procedures involving the
      shoulder or upper arm because the roots of the brachial plexus are most easily
      blocked with this technique. The final needle tip position with this block is
      potentially near the centroneuraxis and arteries perfusing the brain, thus
      careful aspiration of the needle and incremental injection are important. In
      summary, when an understanding of branchial plexus anatomy is combined with
      proper block technique and a patient- and procedure-specific balancing of risk
      benefit, our patients and colleagues will be coadvocates of our branchial plexus
      regional blocks.

PMID- 7825343
TI  - Spinal anesthesia: practical applications.
AB  - The recent widespread popularity of spinal anesthesia can be traced to two
      events. One is the appreciation that, when used for operations below the level of
      the umbilicus, anesthetically induced physiologic trespass is less with spinal
      than with general anesthesia. The other is the recognition that modest
      hypotension with peripheral vasodilation, that may be seen with spinal anesthesia
      or intravenous infusion of nitroprusside, is, unlike hypotension associated with
      hypovolemia, unaccompanied by physiologically significant changes in peripheral
      distribution of cardiac output or changes in the balance between tissue oxygen
      supply and demand in the myocardium or elsewhere. Spinal anesthesia also has
      special advantages specific to urinary tract surgery in the geriatric patient.

PMID- 7825344
TI  - Pain pathways and transmission.
AB  - Pain has been a major concern of humankind since the ancient times, and it
      remains one of the most important subjects of all health care professionals.
      Despite the obvious overwhelming clinical importance, the major advances in its
      diagnosis and therapy have been made only recently. "How do the sensory apparatus
      of the body and system of signal transmission relate to pain of peripheral
      origin?" is the topic of discussion. To do this, it is important to understand
      what constitutes the total pain experience. It consists of: 1) signal
      transduction at the peripheral receptor site, 2) signal conduction along the
      peripheral nerve, 3) pain modulation at the level of the spinal cord, 4) pain
      perception at the supraspinal site, and 5) the associated sensations, emotional
      reactions, and effective state. The signal transmission related to pain may be
      modified by various analgesic agents. Specific analgesic agent has a specific
      site of action which may be at peripheral receptors, at peripheral nerves, at the
      level of the spinal cord, at supraspinal levels by activating descending
      inhibitory systems, or at more cephalad levels by reducing the affective
      component of pain.

PMID- 7825345
TI  - Complications of regional anesthesia for ophthalmic surgery.
AB  - Ocular regional anesthesia can be accomplished with either a peribulbar or
      retrobulbar approach. Each has advantages and disadvantages. Complications can be
      vision-threatening or life-threatening. Positioning the eye in neutral gaze when
      retrobulbar block is executed and using a needle no longer than 31 mm are
      effective strategies to reduce the incidence of serious complications.

PMID- 7825346
TI  - Regional anesthesia for major vascular surgery.
AB  - The relative merits of general vs regional anesthesia for patients undergoing
      major vascular surgery has been the subject of debate over the past decade.
      Previous studies of regional vs general anesthesia often were deficient in
      experimental design and, therefore, did not produce definitive answers. Some of
      these deficiencies related to non-standardized, poorly conducted, and/or
      described general anesthetic techniques, nonstandardized methods of postoperative
      analgesia in the general anesthesia groups, and variations in preoperative
      cardiac status in the study groups. Furthermore, most studies did not
      conclusively demonstrate a cause and effect relationship between the proposed
      mechanisms of the beneficial effect of regional anesthesia and outcome. Recent
      studies, however, have claimed improvements in outcome following regional
      anesthesia in patients undergoing peripheral vascular procedures. The reported
      beneficial effects have included amelioration of the neuroendocrine stress
      response to surgery, improvement in pulmonary function, cardiovascular stability,
      enhancement of lower limb blood flow, reduction in the incidence of graft
      thrombosis, and a reduction in the thrombic response to surgery. Skeptics still
      question whether recent studies have the power to determine whether regional
      anesthesia decreases the incidence of cardiac and pulmonary complications
      following major vascular surgery. Furthermore, the issue of whether the
      beneficial effects of regional anesthesia on the incidence of graft thrombosis
      and the thrombotic response to surgery relating to intraoperative or
      postoperative regional anesthesia/analgesia, to regional anesthesia per se, or to
      the systemic effects of absorbed local anesthetics remains unresolved.

PMID- 7825347
TI  - Toxicity of new spinal agents.
AB  - The clinical success of perispinal administration of opiates for pain relief has
      demonstrated the power of manipulating the neurochemistry of the spinal cord.
      This article briefly discussed reasons for increased interest in new spinal
      agents and some of the issues associated with determining their clinical safety.

PMID- 7825348
TI  - New developments in nondepolarizing muscle relaxants.
AB  - Anesthesiologists perceive that the ideal muscle relaxant is not yet available,
      particularly the nondepolarizing one with a rapid onset and a short duration of
      action. There is also a need for relaxants with different durations of action but
      which would be free from side effects. During the process of this development
      several new compounds have been tested and four have reached an advanced state of
      study; three of these, doxacurium, pipecuronium, and mivacurium are already
      licensed and rocuronium is likely to be licensed in the near future. Doxacurium
      and pipecuronium are slow onset and long duration of action compounds but
      singularly free from cardiovascular side effects. Mivacurium has an onset
      comparable to that of atracurium and vecuronium but with a duration of action
      which is intermediate in duration between these drugs and succinylcholine.
      Rocuronium is a drug with a fast onset of action capable of being used in place
      of succinylcholine but with a duration of action which is similar to that of
      vecuronium.

PMID- 7825351
TI  - Multiple organ dysfunction syndrome.
AB  - The multiple organ dysfunction syndrome (MODS), though newly described, has
      manifested itself in intensive care unit (ICU) patients for several decades. As
      the name implies, it is a syndrome in which more than one organ system fails.
      Failure of these multiple organ systems may or may not be related to the initial
      injury or disease process for which the patient was admitted to the ICU. MODS is
      the leading cause of morbidity and mortality in current ICU practice. While the
      pathophysiology of MODS is not completely known, much evidence indicates that,
      during the initial injury which precipitates ICU admission, a chain of events is
      initiated which results in activation of several endogenous metabolic pathways.
      These pathways release compounds which, in and of themselves, are usually
      cytoprotective. However, an over exuberant activation of these endogenous systems
      results in an inflammatory response which can lead to development of failure in
      distant organs. As these organs fail, they activate and propagate the systemic
      inflammatory response. No therapy has proven entirely efficacious at modulating
      this inflammatory response and the incidence and severity of MODS. In current ICU
      practice, treatment is focused on prevention and treating individual organ
      dysfunction as it develops. With increased understanding of the pathophysiology
      of MODS therapy will come newer modalities which inhibit or interfere with the
      propagation of the endogenous systemic inflammatory response. These newer
      therapies hold great promise and already some are undergoing clinical
      investigation.

PMID- 7825350
TI  - The clinical use of desflurane.
AB  - Desflurane, a newly introduced potent, inhaled anesthetic, differs from its
      predecessors in having a lower solubility in blood and tissues. The lower
      solubility imparts a greater control to the maintenance of anesthesia and a more
      rapid elimination and recovery from anesthesia. In other respects, the
      pharmacological properties of desflurane resemble those of its sister anesthetic,
      isoflurane, currently the most widely-used potent anesthetic in this and other
      countries. The qualitative exceptions to this resemblence are that desflurane is
      more pungent and produces a greater increase in heart rate, particularly at
      deeper levels of anesthesia.

PMID- 7825352
TI  - [Autonomy and human dignity in medicine--ethical and legal questions].

PMID- 7825349
TI  - Monitoring of neuromuscular function in the clinical setting.
AB  - This paper will review the basics of neurostimulation in the perioperative
      period. Following a brief overview of neuromuscular physiology, the mechanism of
      action of depolarizing and non-depolarizing relaxants will be discussed. The
      principles of neurostimulation will then be applied clinically when different
      patterns of stimulation (single twitch, train-of-four, post-tetanic twitch count,
      double burst) are described. Clinical assessment of neuromuscular function will
      then be compared with both subjective and objective means of assessment of
      adequacy of intraoperative relaxation and postoperative reversal. The principles
      reviewed in this paper will then be applied in the clinical setting, and risks
      and benefits associated with perioperative use of muscle relaxants will be
      discussed.

PMID- 7825353
TI  - [Patient autonomy and physician responsibility].

PMID- 7825354
TI  - [Value anamnesis--methods for assessing patient directives].

PMID- 7825355
TI  - [Human dignity and conflict in pregnancy].

PMID- 7825356
TI  - [Examination technique and findings of ultrasound procedures in portal
      hypertension].

PMID- 7825357
TI  - [The physical development of children with histologically verified
      glomerulonephritis].

PMID- 7825358
TI  - [Intensive management of diabetic pregnancy in general practice].

PMID- 7825359
TI  - [Hysteroscopy in diagnosis of the etiology of uterine sterility and infertility].

PMID- 7825360
TI  - [Chronic hepatitis C--clinical course and genotypical pattern of distribution in
      patients of a Berlin infection clinic].

PMID- 7825361
TI  - [Adjuvant therapy with corticosteroids in bacterial "purulent" meningitis-
      obligatory or not indicated?].

PMID- 7825362
TI  - [Incidence of Borrelia burgdorferi in the Greifswald area of the Vorpommern
      region of the Mecklenburg-Vorpommern district].

PMID- 7825363
TI  - [Bilateral lung hypoplasia and pancreas anulare--case report of dizygotic twins].

PMID- 7825364
TI  - [The history of gallstone disease and surgical treatment--250 years planned
      surgery of the bile ducts].

PMID- 7825365
TI  - [Erich Schroder (1893-1968) and social medicine in Berlin].

PMID- 7825366
TI  - [Epidemics and history: the Berlin 1962 dysentery epidemic].

PMID- 7825367
TI  - [Coronary surgery: changes in the patient composition].

PMID- 7825368
TI  - [Changes in indications for surgical coronary revascularization 1985 to 1992].
AB  - We analyzed the changing use of coronary artery bypass grafting in our
      institution during the years from 1985 to 1992. All clinical parameters
      indicating an increased perioperative risk for the surgical intervention
      increased during the study period (increased percentage of old patients, females,
      patients with severe coronary artery disease (high modified Gensini-index or
      triple-vessel disease), and left main stenoses). During a 2-year follow-up there
      was a constant proportion of patients with a good postoperative clinical result;
      perioperative mortality as well as global and cardiac 2-year mortality showed no
      significant changes. Despite an increased proportion of patients with higher
      perioperative risk the acute and long-term results of coronary artery bypass
      surgery in our study were quite satisfactory. This must be attributed to
      improvements in operative techniques, improved personal skills of the surgeons,
      and improvements in perioperative treatment and critical care.

PMID- 7825369
TI  - [Principles of duplex ultrasound diagnosis of the internal thoracic artery].
AB  - Because of its better long term patency the internal thoracic artery has become
      the conduit of choice for myocardial revascularization. Thirty healthy young
      volunteers were investigated to prove the suitability of the duplex system for
      investigating the internal thoracic artery. The mean systolic peak flow velocity
      was 1.15 m/s in the proximal vessel decreasing to 0.55 m/s in the peripheral
      course of the artery. Mean internal thoracic artery diameters at the origin were
      calculated as 2.18 mm for the left and 2.43 mm for the right internal thoracic
      artery. The flow curves represent those of elastic-type vessels, whereas in a
      small number resistance curves occurred representing the muscular type. The
      combination of two-dimensional B-mode and Doppler unit allows visualization of
      the internal thoracic artery and assessing the flow velocities within the vessel.
      Ultrasonic duplex scanning is a noninvasive diagnostic tool for investigation of
      the internal thoracic artery.

PMID- 7825370
TI  - [Incidence of myocardial bridges after adrenergic stimulation and decreasing
      afterload in patients with angina pectoris, but normal coronary arteries].
AB  - The prevalence of myocardial bridging in patients with angina pectoris but normal
      coronary arteries was evaluated in 1780 patients who consecutively underwent
      coronary angiography. 62 patients (3.5%) were free of coronary atherosclerosis or
      other organic heart disease. In four of these patients systolic narrowing of the
      LAD was present. The other 58 patients received 0.2 mg nitroglycerin (NTG)
      intracoronarily and 30 micrograms/ml orciprenalin (ORC) intravenously up to a
      heart rate of 130/min. Repeated angiography revealed systolic compression of the
      LAD due to myocardial bridging (MB) in 40% (25 of 62). The length of MB raised
      from 1.4 +/- 0.9 cm to 2.1 +/- 1.1 cm (p < 0.001) after NTG and to 2.8 +/- 1.1 cm
      (p < 0.001) after ORC. Coronary luminal stenosis increased from 48 +/- 29% to 67
      +/- 25% after NTG (p < 0.001) and to 83 +/- 18% (p < 0.001) after ORC. The
      prevalence of myocardial bridging in 40% of patients with stress-induced angina
      pectoris but normal coronary arteries is high. Nearly always coronary compression
      by myocardial bridging is only evident after adrenergic stimulation or after
      afterload reduction. Therefore, NTG and ORC are useful drugs to facilitate
      diagnosis of myocardial bridging by increasing coronary compression.

PMID- 7825371
TI  - [Symptomatic and asymptomatic myocardial ischemia before and after percutaneous
      transluminal coronary angioplasty].
AB  - The aim of the present study was to prove the effect of successful percutaneous
      transluminal coronary angioplasty (PTCA) on the occurrence of symptomatic and
      silent myocardial ischemia recorded during 24-h ECG, considering the number of
      diseased coronary arteries, a history of myocardial infarction, and the interval
      between myocardial infarction and PTCA. Before PTCA, 28 of 56 patients (50%) had
      ischemic ST-segment alterations, 3-8 days thereafter, there were only 13 patients
      (23%) with signs of myocardial ischemia (p < 0.01). The number of episodes of
      ischemia (IE) was reduced 44% (p < 0.05), their duration (ID) 51% (p < 0.01). In
      symptomatic patients, the decrease was 67% (p < 0.05) and 83% (p < 0.05), in
      patients with silent myocardial ischemia 20% (n.s.) and 29% (n.s.). Patients with
      one-vessel disease exhibited a 73% reduction of IE (p < 0.01) and a 85% reduction
      of ID (p < 0.01). In patients with two-vessel disease, the decrease was 47% (p <
      0.05) and 26% (p < 0.05), whereas in those with three-vessel disease, there was
      no significant change. Patients without stenosis (< 50%) after PTCA had-
      irrespective of primary findings--a decrease of IE of 78% (p < 0.05) and of ID of
      85% (p < 0.05), while patients with persisting coronary artery stenosis exhibited
      no significant decrease (20% and 35%, n.s.). In patients without history of
      myocardial infarction, the reduction of IE was 79% (p < 0.01) and that of ID 85%
      (p < 0.05); in patients with recent myocardial infarction (< 3 months) the
      decrease was 59% (p < 0.05) and 70% (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7825372
TI  - [Therapy with beta receptor blockers in myocardial infarct].
AB  - During the last 10-15 years, a total of 49 prospective, randomized, controlled
      studies have been performed to evaluate the efficacy and safety of early
      administered beta-receptor antagonists in patients with acute myocardial
      infarction. Those trials in which beta-receptor antagonists were administered
      intravenously followed by oral medication within 72 h after the onset of symptoms
      reported a significant reduction in early mortality (on average 13%; 95%
      confidence interval -2% to -25%). The efficacy of beta-receptor antagonists in
      reducing mortality was particularly obvious in patients at higher risk (i.e.,
      older patients, previous infarction) with the maximal efficacy observed during
      the first 3-4 days of therapy. Similarly, there was a reduction in the incidence
      of reinfarction which averaged 19% for the patients treated with beta-receptor
      antagonists. The metaanalysis also showed a significant reduction in the
      incidence of nonfatal cardiac arrest due to primary ventricular fibrillation for
      the group receiving beta-receptor antagonists (average risk reduction 16%; 95%
      confidence interval -2% to -30%). As calculated on the basis of the ISIS-1 data,
      treatment with beta-receptor antagonists in approximately 200 patients with acute
      myocardial infarction would lead to the avoidance of one death, one reinfarction,
      and one episode of ventricular fibrillation. Based on these data, it is
      recommended that administration of beta-receptor antagonists should be an
      important adjunctive therapeutic modality in patients with acute myocardial
      infarction and no contraindications for this form of treatment.

PMID- 7825373
TI  - [Cardiovascular risk factors in patients over 65-years of age in Germany. Results
      of the STEPHY Study (Starnberg Trial on Epidemiology of Parkinsonism and
      Hypertension in the Elderly)].
AB  - The aim of the study was to assess the current cardiovascular risk factor profile
      including data on treatment of a representative population over the age of 65 in
      Germany. From a total of 1190 inhabitants > or = 65 years living in two Bavarian
      villages near Munich, 982 could be visited at home ("door-to-door" survey), where
      a questionnaire and the measurement section were performed (response rate 82.5%).
      Blood pressure was measured three times in the sitting position with a standard
      sphygmomanometer, ("actual") hypertension was defined as systolic blood pressure
      > or = 160 mm Hg and/or diastolic blood pressure > or = 95 mm Hg or effective
      antihypertensive treatment. Obesity was defined as body mass index > or = 27.8
      kg/m2 for men or > or = 27.3 kg/m2 for women, hypercholesterolemia as total
      cholesterol > or = 250 mg/dl (6.5 mmol/l), diabetes as fasting serum glucose >
      120 mg/dl, glucosuria or treatment with insulin or oral antidiabetics. With a
      prevalence of 53% hypertension was the leading risk factor, followed by obesity
      with 35% and hypercholesterolemia with 21%; smoking and diabetes were observed in
      < 10%. Hypertension and obesity tended to be more prevalent in women, diabetes in
      men; hypercholesterolemia was significantly more prevalent in women. While the
      prevalence of hypertension increased up to the age groups "75-79 years" in men
      and "80-84 years" in women, there was a constant decrease with age for obesity,
      hypercholesterolemia and smoking. Three-quarters of the participants showed a
      minimum of one cardiovascular risk factor, the risk factor combination
      "hypertension/hypercholesterolemia/smoking" was observed however only in
      1%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7825374
TI  - [Quantitative evaluation of myocardial perfusion with ultrafast magnetic
      resonance tomography].
AB  - With the advent of ultrafast Magnetic Resonance Imaging (MRI), it is now possible
      to produce images with high temporal resolution. This gives the opportunity to
      record the passage of the paramagnetic contrast material Gadolinium-DTPA through
      the tissue of the heart muscle, yielding information on regional myocardial
      perfusion. We assessed the accuracy of MRI to detect and quantify reductions in
      coronary flow secondary to stenosis in dogs and patients. Regional blood flow was
      measured in dogs by left atrial injection of microspheres labeled with different
      radioactive isotopes. Signal intensity (SI) curves were generated in regions of
      interest over the myocardium and the cavum of the left ventricle. A newly
      developed two-compartment model based on the indicator-dilution method was used
      for interpretation of the SI-curves. In an optimization process the free
      parameters of the model equation were fitted to the measured SI-curves. The
      following flow parameters were determined: model parameter Q*, time to peak
      intensity (T), maximum signal intensity (SImax) and mean transit time (MTT) as
      calculated from a gamma variate fit. Absolute blood flow values were calculated
      for the parameters MTT and Q* assuming that the intravascular volume represents
      10% of the total myocardial tissue volume. Measurements were performed on a 1.5 T
      Magnetom SP (Siemens AG, Erlangen) using a Turbo Flash sequence (TR = 6.5 ms, TE
      = 3 ms, TI = 100 ms, Flip Winkel = 9 degrees). Endsystolic images (voxel size =
      1.8, 2.7, 15 mm3) were taken with an 18-cm Helmholtz surface coil in the short
      axis view. A Gd-DTPA bolus (0.05 mmol/kg) was injected into the left atrium of 3
      anesthetized closed-chest dogs. From the myocardial SI-curves the different
      parameters of myocardial perfusion were compared with flow assessed by
      microsphere injection over a wide range of myocardial blood flows (from 0.04
      ml/min/g to 7.6 ml/min/g). A third-order polynominal fit showed a good
      correlation for the parameter Q* and MTT, whereas T and SImax were found to have
      a poor correlation. The linear regression analysis for a limited range of < 2
      ml/min/g showed a superior estimation of myocardial perfusion for the parameter
      Q* than MTT. Blood flow > 2 ml/min/g was significantly underestimated by the MRT
      measurements, but the parameter Q* showed the smallest amount of the divergent
      changes.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7825375
TI  - [Mechanism of action of directed coronary atherectomy].
AB  - The mechanism of directional coronary atherectomy (DCA) results from tissue
      removal and mechanical dilation ("Dotter" effect, balloon inflation). To estimate
      the concomitant contribution of dilation to lumen enlargement by DCA, we
      determined the amount of retrieved tissue and the change of luminal volume
      (computer-based quantitative coronary artery analysis) and compared both. The
      first 25 patients undergoing DCA in 1992 were enrolled in this study. In all
      cases DCA was successful (tissue removal, residual stenosis < 50%, absence of
      major complications). The diameter stenosis was reduced from 68 +/- 11% to 10 +/-
      24% (p < 0.001). Calculated luminal volume increased from 1.04 +/- 0.46 mm to 2.9
      +/- 0.64 (p < 0.001). The comparative value of the adjacent reference segment was
      a luminal diameter of 3.23 +/- 0.56 mm. The increase of the calculated luminal
      volume was 23 +/- 13 mm3. The average weight of removed tissue was 11 +/- 7 mg.
      The calculated "atherectomy index" (ratio of tissue volume retrieved to change in
      luminal volume) revealed a significant correlation between both volumina and
      averaged 0.502 for the whole group. The results show that the mechanical
      component plays an important part in the mechanism of luminal enlargement in
      addition to tissue removal and therefore could be a possible explanation for the
      high rate of restenosis after DCA, which was documented in the recently published
      big DCA trials.

PMID- 7825376
TI  - [Cerebral circulation in patients with dilated cardiomyopathy and aortic valve
      diseases].
AB  - The present study was performed in order to investigate the effect of dilated
      cardiomyopathy and severe aortic valve disease on cerebral blood flow. Cerebral
      perfusion was determined in 39 healthy volunteers representing two control groups
      of different age (77.7 +/- 8.7; 79.7 +/- 8.1 ml/100 g/min), in 7 patients with
      dilated cardiomyopathy (64.0 +/- 4.7 ml/100 g/min), in 11 patients with severe
      aortic stenosis (71.1 +/- 14.8 ml/100 g/min), and in 6 patients with severe
      aortic regurgitation (54.6 +/- 5.8 ml/100 g/min). Regional cerebral blood flow
      was measured with the 133Xenon inhalation method. Cerebral blood flow in severe
      aortic regurgitation patients (p = 0.006) was markedly and significantly reduced
      versus controls, whereas in dilated cardiomyopathy patients (p = 0.197) and in
      patients with severe aortic stenosis (p = 0.111) cerebral blood flow was not
      significantly reduced. A chronic adaptation of cerebral blood flow to the
      profound reduction of cardiac output is assumed in dilated cardiomyopathy
      patients. The collapsing pulse and the maximal reduction of mean arterial blood
      pressure in severe aortic regurgitation patients cause the reduction of
      autoregulatory capacity of cerebral blood flow with subsequent decrease of brain
      perfusion. Measurement of cerebral blood flow appears to be suitable for
      evaluation of perfusion deficits due to cardiac abnormalities. It provides an
      additional parameter for estimating the indication of valve replacement in
      patients with aortic valve disease.

PMID- 7825377
TI  - [Perfusion of the left ventricular myocardium in patients with aortic valve
      diseases using single photon emission computerized tomography].
AB  - To determine resting myocardial perfusion in 30 patients with aortic valve
      disease (AVD) TI-201 emission computer tomography (ECT) studies and heart
      catheterization were performed. 16 patients had a predominant aortic
      regurgitation (AR); an aortic stenosis (AS) was found in 14 patients at
      catheterization. Perfusion defects were documented in 10 of 16 patients with AR,
      and in 5 of 14 patients with AS. Regional determination demonstrated in 10 of
      these 15 abnormal cases at least one of the perfusion defects in the postero
      basal segment. In patients with aortic valve disease and normal myocardial
      perfusion scintigraphy, the ejection fraction (EF) was significantly higher (p <
      0.05) as compared to the patients with abnormal TI-201 ECT (EF 65.2 +/- 15.0% vs.
      58.9 +/- 15.1%). Additionally, in the 15 patients with abnormal TI-201 ECT, the
      left ventricular end-diastolic volume index (LVEDVI) and the left ventricular end
      systolic volume index (LVESVI) were both increased (LVEDVI in AVD: 130.3 +/- 15.3
      ml/m2 vs. 107.4 +/- 13.6 ml/m2, LVESVI in AVD: 61.9 +/- 14.6 ml/m2 vs. 48.0 +/-
      9.8 ml/m2). In conclusion, left ventricular perfusion defects at rest can be
      detected by TI-201 ECT in many patients with aortic valve disease. Such
      myocardial perfusion defects indicate left ventricular enlargement and impaired
      left ventricular function, especially in patients with aortic regurgitation.

PMID- 7825378
TI  - [Guidelines for catheter ablation in patients with tachycardic arrhythmias.
      German Society of Cardiology--Cardiovascular Research].

PMID- 7825379
TI  - [The melatonin content of the tissues of relatively wild and domesticated silver
      foxes Vulpes fulvus].
AB  - Pineal, plasma and retina melatonin content and its diurnal dynamics have been
      studied in adult relatively wild and domesticated female silver foxes. Diurnal
      cyclicity of melatonin concentration in these tissues was observed with a minimum
      during the day time, maximum in the middle of the night and intermediate level in
      the evening. Circadian melatonin dynamics was pronounced in non-domesticated as
      much as in domesticated females. However, since the pineal mass in domesticated
      animals is significantly smaller than in wild ones, the quantity of the hormone
      per 1 mg of the pineal tissue at night was much higher in the former. At the same
      time, plasma concentration of melatonin in both groups was the same. A possible
      cause of higher melatonin concentration in the pineal organ of domesticated foxes
      is discussed.

PMID- 7825381
TI  - [The neurochemical mechanisms of the influence of the posterior hypothalamus on
      the electrical activity of the forebrain hemispheres and on autonomic reactions
      in hens].
AB  - Effects of i.v. administration of N- and M-cholinergic blocking agents ganglerone
      and atropine and alpha- and beta-adrenergic blocking agents phentolamine and
      obsidan (propranolol) on reaction of desynchronisation of EEG and on autonomic
      reactions (arterial blood pressure, heart and respiratory rates) evoked by low-
      and high frequency stimulation of the posterior hypothalamus were studied in
      hens. It was shown that atropine induces a pharmacological dissociation of
      ascending and descending influences of the hypothalamus by blocking the
      desynchronizing mechanisms of the upward discharge of the hypothalamus without
      any apparent changes of autonomic reactions. It was found that the effects of
      adrenoblocking agents are diametrically opposite to that of atropine in regard to
      the EEG component, as well as the autonomic components of hypothalamically
      induced activation reaction. Peculiarities of evolutionary development of
      neurochemical structures of ascending and descending systems of the hypothalamus
      are discussed.

PMID- 7825380
TI  - [The development of water-electrolyte homeostasis during normal and disordered
      embryogenesis in rats].
AB  - It has been shown that venous congestion both in mother and in foetus affects
      water and salt content with a tendency to decrease the latter, the effect being
      more significant in the foetus. Prolonged pregnancy did not affect water and salt
      metabolism in tissues of adult rats, whereas accumulation of liquid was found in
      foetuses. Water deprivation did not result in significant changes of water and
      salt balance in tissues. The role of extraembryonic organs in formation of hydro
      ionic balance of the foetus under various conditions of pregnancy was revealed.

PMID- 7825382
TI  - [A comparative study of the organization of the circadian cycle of wakefulness
      sleep in normal rats and rats with a genetic predisposition to audiogenic seizure
      attacks].
AB  - Studies on the structure of the diurnal wakefulness-sleep cycle and spectral EEG
      parameters of the hippocampus, somatosensory, visual and auditory cortical zones
      have been made in rats (strain KM) genetically predisposed to audiogenic
      seizures. It was shown that in the paradoxical phase of sleep in these animals
      (in contrast to Wistar rats), the stage of the hippocampal theta rhythm is
      significantly reduced, whereas the duration of a stage of domination of alpha
      rhythm in the neocortical and hippocampal EEG is increased. No spontaneous
      epileptiform spike and spike-wave discharges were observed in the EEG pattern of
      KM rats. The role of ascending activating systems in organization of the
      paradoxical phase of sleep is discussed.

PMID- 7825383
TI  - [The regulation of the wakefulness-sleep cycle in normal rats and during sleep
      pathology].
AB  - Studies on the cycle wakefulness-sleep in rats with genetic predisposition to
      catalepsy revealed that this strain may be also used for investigation of sleep
      pathology. These animals exhibit abnormal regulation of the cycle which reveals
      itself in the onset of a "hypnotic" sleep phase. This phase is a result of a
      special form of sleep regulation and it cannot be classified as slow-wave or
      paradoxical sleep. In the hypnotic phase, no increase in spatial and temporal
      synchronization between structures was observed which is typical of the normal
      delta-sleep (0.704 +/- 0.053). Correlation connections between the visual cortex
      and subcortical structures remained weak (0.326 +/- 0.076) in spite of the
      increase in the level of EEG synchronization close to that during slow-wave
      sleep. It was shown that catalepsy may be due to lack of dopamine.

PMID- 7825384
TI  - [Aldosterone receptor binding and the physiological response to the hormone in
      adult rats subjected in early ontogeny to a single increase in the level of the
      hormone in the blood].

PMID- 7825385
TI  - [The ontogenetic characteristics of the coordination relationships between the
      hemicenters of the spinal motor pacemaker in rat pups].
AB  - In experiments on rat puppies of the first month of postnatal life, under the
      conditions of real motor behaviour (spontaneous periodic motor activity) and the
      evoked motor reactions (late prolonged motor discharges), studies have been made
      on the development of coordination relationships between antagonists of the same
      extremity and between homologous muscles of the hindlimbs. In was found that
      irrespectively of the early onset of reciprocal excitation of antagonists, the
      mechanisms of this activity are not mature. Maturation of bilateral coordinations
      takes place at later stages. It was noted that one of the hemicenters of the
      spinal motor pacemaker is capable of producing rhythmic or constant activity
      which is not related to the pattern of the activity in the other hemicenters of
      the pacemaker of the same extremity or hemicenters of pacemaker of homologous
      extremity. Administration of DOPA causes the disturbance of coordination
      relationships.

PMID- 7825386
TI  - [The effect of the negative reinforcement system on the nonspecific nociceptive
      system of the thalamus in 41- to 60-day-old rabbits].
AB  - The work has been carried out in two steps. At the first one, in behavioural
      experiment, "punishment zones" were identified in animals, at the second step, in
      acute experiment, studies were made of the effect of stimulation of these zones
      on EP registered in CM-Pf in response to peripheral nociceptive stimulation. It
      was shown that stimulation of "punishment zones" inhibits the EP at currents
      lower critical level at which no avoidance reaction could be observed in
      behavioural experiment. Changes in the amplitude and duration of the EP depend on
      the aversive reaction to stimulation of these zones in the behavioural
      experiment. The sensitivity of CM-Pf to electrical stimulation of "punishment
      zones" remains constant with age.

PMID- 7825388
TI  - [A microdissection study of the kidney in the great gerbil Rhombomys opimus in
      early postnatal ontogeny].
AB  - It has been demonstrated that in gerbils, similar to other mammals, superficial
      nephrons are formed in postnatal ontogenesis in the last turn. However, the
      development of these nephrons and thin parts of Henle's loops in intracortical
      and juxtamedullary nephrons takes place earlier than in other mammals, which may
      be caused by specialization of gerbils to arid conditions.

PMID- 7825387
TI  - [The ultrastructural characteristics of the synapses during the acquisition of a
      passive avoidance reaction and of imprinting in chicks].
AB  - Studies on morphometric parameters of synapses in the visual projection zone of
      the accessory and associative zone of the ventral hyperstriatum in both
      hemispheres of the brain in 4-day chicks after visual imprinting and alimentary
      aversive learning revealed specific changes in the longevity of postsynaptic
      dense regions and in the number of vesicles in active zone. The role of the
      structures studied in sensory perception, learning and memory is discussed.

PMID- 7825389
TI  - [The spread of the ideas and influence of L. A. Orbeli among biologists].

PMID- 7825390
TI  - [Comparative physiology and the problems in the evolution of external
      respiration].

PMID- 7825391
TI  - [The functions of sleep].

PMID- 7825392
TI  - [The structural-functional characteristics of the GTP-binding proteins in
      invertebrate animals].

PMID- 7825393
TI  - Sodium lauryl sulfate and recurrent aphthous ulcers. A preliminary study.
AB  - Sodium lauryl sulfate (SLS), a synthetic detergent commonly used in dentifrices,
      is an effective denaturant. The aim of the present study was to investigate the
      effect of SLS in patients with recurrent aphthous ulcers (RAU). Ten patients with
      multiple minor RAU participated in the study. The mean incidence of RAU was 17.8
      during a 3-month period before the study. The patients used a dentifrice
      containing 1.2% SLS for a test period of 3 months followed by a dentifrice
      without SLS for the same time period. The results showed a statistically
      significant decrease in the number of aphthous ulcers from 14.3 after using the
      SLS-containing dentifrice to 5.1 ulcers after brushing with the SLS-free
      dentifrice (p < 0.05). It is suggested that the denaturing effect of SLS on the
      oral mucin layer, with exposure of the underlying epithelium, induces an
      increased incidence of RAU.

PMID- 7825394
TI  - Discrimination ability in patients with extensive fixed partial dentures on
      mandibular canine teeth.
AB  - To study discrimination ability under different test situations, a
      psychophysiologic test was performed in a group of patients with 12-unit
      mandibular fixed partial dentures supported on the 2 canines. The cantilever
      segments were exchangeable. Analyses of discrimination ability were performed
      with regard to periodontal and endodontic status of the abutment teeth and to
      type of mucosal contact in cantilever regions. Discrimination ability was
      markedly reduced with a strongly reduced periodontal bone contact area. The
      endodontic status did not affect discrimination ability. A tendency towards
      better discrimination ability was seen when the cantilever sections without
      mucosal contacts were compared with those with mucosal contacts through pontics
      or saddles.

PMID- 7825396
TI  - Longitudinal changes in craniomandibular dysfunction in an elderly population in
      northern Sweden.
AB  - Longitudinal changes and cohort differences in craniomandibular dysfunction (CMD)
      were studied in a 79-year-old cohort (n = 65) and in 70-year-old cohorts in 1981
      (n = 62) and 1990 (n = 60) by means of interview and clinical examination.
      Although the frequency of reported CMD symptoms decreased, many clinical signs of
      CMD increased during the 9-year observation period. Women reported more symptoms
      and showed more signs of CMD than men, and a great many of the clinical signs
      registered in 1981 still persisted in 1990. The 70-year-old cohort studied in
      1990 showed a lower frequency of reported symptoms of CMD and of
      temporomandibular joint pain on palpation and a higher frequency of muscle pain
      and mandibular deviation than the 70-year-olds examined in 1981.

PMID- 7825395
TI  - Evaluation of information on dental health care at child health centers. Factors
      in caries prevention--opinions of dental personnel and their relation to parental
      attitudes.
AB  - Our aim was to study, by means of questionnaires, some specific opinions of
      dental personnel, giving information on dental health care at child health
      centers and Public Dental Service clinics. The questions dealt with the relative
      importance of dietary habits, oral hygiene, and fluoride for the occurrence of
      caries in small children and why some children develop caries. The material
      consisted of dentists, dental hygienists, and dental assistants, participating in
      1983 and/or 1992. The results showed that, on the whole, the different categories
      had similar opinions. In both 1983 and 1992 diet was ranked first, oral hygiene
      second, and fluoride third, but the distribution of priorities changed. In 1992
      the priority values for oral hygiene were more dispersed over the priority grades
      and those for fluoride considerably higher than in 1983. In contrast, parents of
      4-year-old children interviewed in 1983 stated that toothbrushing is more
      important for dental health than diet. To the question why some children develop
      caries, most of the personnel responded that parents lack motivation to convert
      advice into practice. Besides unsatisfactory dietary habits and insufficient oral
      hygiene, deficiencies in the information process were other frequently quoted
      factors.

PMID- 7825397
TI  - Variation in clinical time spent by dentist and dental hygienist in child dental
      care.
AB  - In a field project in the Public Dental Service in Norway, 4000 children aged 5
      to 18 years were examined and given preventive care by dental hygienists. The
      study describes the clinical time spent providing child dental care when
      hygienists examined all children and referred to dentists those children who
      required care hygienists were not qualified to deliver. Of all clinical time
      spent, 56% was dentist time and 44% was hygienist time. A high proportion of
      children without dental caries did not consume dentist resources at all. More
      than 40% of the dentist time was consumed by the 10% of the children with most
      new decayed teeth. In conclusion, the project showed that in a child population
      with low caries increment, a substantial proportion of children received all
      dental care from hygienists, so that dentist resources were saved for other
      groups. However, although hygienists were used as first-line personnel, a
      considerable quantity of dentist time was spent on dental care for children.

PMID- 7825398
TI  - Flexural strength of two electro-plated dental ceramics.
AB  - This study aimed to investigate the influence on flexural strength of electro
      plating two dental porcelains, Vita Omega and Vita Omega 800. The porcelains were
      treated in accordance with the manufacturer's instructions, and the specimens
      were produced following the ISO 6872 standard for rectangular bars. Specimens
      were divided into three groups, of which none, one, or three of the surfaces were
      plated with a thin layer of gold. Flexural strength was tested with a three-point
      bending test. Ten specimens were tested for each combination of porcelain and
      plating, for a total of 60 test pieces. For both porcelains, a significantly
      higher flexural strength was found for the specimens furnished with a gold layer.
      The number of covered surfaces did not significantly influence the tested
      strength. This increase in strength is most likely due to decreased crack
      initiation and fracture propagation after the covering of random defects in the
      porcelain. A better stress distribution might also be anticipated and partly
      explain the results.

PMID- 7825400
TI  - Root length, crown height, and root morphology in Turner syndrome.
AB  - Root length, crown height, and root morphology were studied on intraoral and
      panoramic radiographs in 33 Turner syndrome patients aged 7.0-16.7 years,
      subdivided on the basis of karyotype. Thirty-three normal girls aged 10.2-16.4
      years served as controls. In the 45X patients and, with the exception of a few
      teeth, also in the isochromosome and mosaic karyotypes, root length and crown
      height of incisors, canines, and premolars were significantly reduced. Some teeth
      showed altered crown-root proportions. Maxillary first premolars showed a
      significantly increased number of two-rooted and three-rooted variants.
      Mandibular premolars and molars had a complex root morphology, and a
      classification system was established including four premolar and six molar root
      types. Premolars had a significantly increased number of root components. Some of
      the variants, such as a molar-like second premolar, are apparently specific for
      these patients. On several first molars a radix entomolaris was identified. Two
      separate mesial and one or two separate distal roots were also frequently seen.
      Our investigation demonstrates that X-chromosome deficiency influences root
      formation.

PMID- 7825399
TI  - Site-related streptococcal attachment to buccocervical tooth surfaces. A
      correlative micromorphologic and microbiologic study.
AB  - Scanning electron (SEM) microscopy of epoxy replicas made from dental impressions
      has shown that in buccal gingival recession the root surfaces are devoid of
      cementum, leaving the dentin exposed. In this study replication techniques were
      applied to correlate the micromorphology of the buccocervical region with early
      streptococcal attachment. The subjects were 27 healthy young adults. The
      buccocervical surfaces of all the premolars were meticulously cleaned. The
      subjects fasted for 2 h before impression-taking. Replicas were made from
      impressions in hydrophilic A-silicone, and streptococcal attachment was
      visualized by light microscopy of mitis-salivarius agar replicas incubated
      anaerobically for 48 h. The surface micromorphology was documented by SEM of
      corresponding epoxy replicas. Colonization only 2 h after cleaning was very
      sparse. Sites with healthy or inflamed gingivae had markedly different
      colonization patterns in the sulcular region. In 4 subjects with a total of 12
      sites where gingival recession, undetected clinically, was disclosed by SEM,
      representative colonies were retrieved and identified microbiologically to
      species level. Two healthy sites per subject were also sampled. Streptococcus
      mutans and S. sobrinus were identified from eight sites with exposed root dentin.
      S. oralis predominated on the enamel surfaces. The method offers a valuable
      complement to in situ and in vitro microbiologic studies of exposed dentin and a
      novel technique for sampling clinical isolates of streptococci.

PMID- 7825401
TI  - How different curing methods affect the degree of conversion of resin-based
      inlay/onlay materials.
AB  - The purpose of this investigation was to measure the conversion of five inlay
      materials with different curing methods. In particular, the influence of
      secondary curing in light ovens--that is, additional curing with light and heat
      simultaneously--was evaluated. The conversion was determined by infrared multiple
      internal reflection spectroscopy. The inlays were cured with three curing methods
      (A, B, and C). The conversion was recorded immediately after ended curing and
      after an additional storage period (postcuring). The mean conversion with method
      A, using a handheld curing unit, was 42.1% and increased significantly to a mean
      of 55.4% during the storage period at (37 +/- 1) degrees C. Both curing methods B
      and C, including the use of light ovens, gave a mean conversion of 65%, which did
      not increase significantly during the storage period. This investigation
      demonstrated that the degree of conversion depends on the curing method used.

PMID- 7825402
TI  - Ocular and cerebral blood flow measurements in healthy subjects. A comparison of
      blood flow velocity and dynamic tonometry measurements before and after
      acetazolamide.
AB  - The ocular and cerebral blood flow was studied in 15 healthy subjects using
      transcranial Doppler ultrasonography (2 MHz). The blood flow velocity in the
      precerebral carotid arteries, in the ophthalmic artery and in the middle cerebral
      artery was measured under baseline conditions and after i.v. administration of 1
      g acetazolamide. To measure the intraocular pressure and the corneal indentation
      pulse amplitude, a dynamic tonometer was used. Pulsatile ocular blood volume was
      calculated from these values. After one single dose of acetazolamide a
      significant decrease in ophthalmic artery flow velocity, and a significant
      increase both in internal carotid and in middle cerebral artery velocity was
      found. A significant decrease in intraocular pressure and in pulsatile ocular
      volume after acetazolamide was also demonstrated. These findings suggest that the
      acute effect of acetazolamide may be associated with a reduced ocular blood flow,
      explaining some of the reduction in IOP.

PMID- 7825403
TI  - Transretinal histopathological changes in capillary-free areas of diabetic
      retinopathy.
AB  - The histopathology of capillary-free areas in diabetic retinopathy was studied in
      27 lesions from 12 human donor eyes. Localised capillary-free areas were
      identified on casts of the retinal vascular system, and on subsequent
      histological sections of these areas the casted vessels acted as points of
      reference to accurately combine the histological appearance of the retina with
      the vascular morphology as seen on the cast. All studies lesions showed inner
      retinal changes with loss of ganglion cells, attenutation of the inner nuclear
      layer and hyalinization of the retinal capillary network. In 21 of the studied
      lesions a homogeneous eosinophil substance was seen accumulated between the
      photoreceptor outer segments and the retinal pigment epithelium corresponding to
      the areas with inner retinal changes. The findings may help explain the blocking
      of choroidal fluorescence in capillary-free areas as seen on fluorescein
      angiograms in diabetic retinopathy. The study suggests future guidelines for
      further illumination of the pathophysiology of proliferative diabetic
      retinopathy.

PMID- 7825404
TI  - Echographic classification of intraocular tumours. A 15-year retrospective
      analysis.
AB  - The data on echographic routine diagnosis of intraocular tumours (prominence
      equal to, or larger than 2 mm) during the years 1976-1990 in the authors'
      department, were analyzed by multivariate statistical methods, using the final
      diagnosis either from pathology after enucleation or from the confirmed clinical
      diagnosis. The material consisted of melanomas (n = 325), metastases (n = 44),
      haemangiomas (n = 19) and other intraocular tumours (n = 16). The best set of
      echographic parameters in descending order of significance was: reflectivity (A
      mode), choroidal excavation (B-mode), shape (B-mode), and regularity (A/B mode).
      Echographic differentiation by computer analysis of data on the three main kinds
      of tumours (melanoma/metastasis/haemangioma) separate from all the remaining
      tumours was expressed by the correct fraction: melanoma 89%, metastasis 80% and
      haemangioma 97%. The clinical echographic classification for these cases was 89%,
      93% and 99.5%, respectively. The simultaneous differentiation between the three
      classes was found to yield a correct fraction of 85% by computer statistics and
      95% by routine echography. The results of the present study might be used for
      prospective classification through the use of the parameter 'knowledge base'
      contained in the statistical classification procedure.

PMID- 7825405
TI  - The effect of treatment on the results of high-pass resolution perimetry in
      glaucoma.
AB  - In order to find out to which extent high-pass resolution perimetry would detect
      any changes in patients treated for glaucoma, resolution perimetry results were
      evaluated from 56 glaucoma patients and 15 untreated ocular hypertensive patients
      followed for 2 to 3 years. Fifty-nine of the 71 examined patients showed lower
      resolution thresholds, i.e. increased sensitivity, after 2 years, compared to
      initial values. The threshold decrease was significantly larger in the treated
      glaucoma patients (median 1.22 dB) than in the untreated ocular hypertensive
      patients (0.48 dB). The threshold decrease in the untreated ocular hypertensive
      group corresponds to the previously described learning effect. In 35 of the 56
      treated glaucoma patients the thresholds improved more than 0.84 dB, the upper
      confidence limit in the untreated group, which may indicate a beneficial effect
      of antiglaucoma therapy in these patients. The threshold change was unrelated to
      initial resolution threshold and cannot be explained by a 'sorting' effect. The
      observations in the current study using resolution perimetry indicate that
      improved visual function can be demonstrated in many patients treated for early
      glaucoma, at least during the first 2 years of treatment.

PMID- 7825406
TI  - Filter goggles imitating dark adaptation for measurement of visual readaptation
      after flash exposure.
AB  - The effect of red pass goggles (cut off wavelength = 650 nm) imitating dark
      adaptation on measurement of visual readaptation after flash exposure was
      investigated in humans. The results showed that there is no statistically
      significant difference between visual readaptation time measured with ordinary
      dark adaptation and that with goggles for adaptation. No statistically
      significant difference was found between females and males. It is suggested that
      red pass goggles can be practicably used to simulate dark adaptation in measuring
      visual readaptation time. Visual readaptation time was measured as the interval
      between the triggering of a green flash and the reappearance of optokinetic
      nystagmus. Optokinetic nystagmus was induced by a moving vertical grating and
      recorded by DC EOG.

PMID- 7825407
TI  - Ocular surface damage and tear lactoferrin in dry eye syndrome.
AB  - We studied the relationship between the severity of ocular surface damage and the
      level of tear lactoferrin in primary and secondary Sjogren's syndrome and
      keratoconjunctivitis sicca not associated with Sjogren's syndrome. A significant
      negative correlation was found between Rose Bengal staining score and level of
      tear lactoferrin in all three groups. Analysis of covariance disclosed no
      significant differences in regression lines for Rose Bengal staining score vs
      tear lactoferrin level among the three groups. The three regression lines
      appeared to be identical to each other. These findings indicate that the severity
      of ocular surface damage due to dry eye largely depends on the tear secretory
      function of the lacrimal gland, and that the function of the lacrimal gland can
      be evaluated by determination of level of tear lactoferrin using the same
      standards regardless of differences in pathogenesis of underlying diseases.

PMID- 7825408
TI  - Topical cyclosporin treatment of keratoconjunctivitis sicca in secondary
      Sjogren's syndrome.
AB  - Topical cyclosporin 2% in olive oil was investigated for its possible
      immunoregulatory role on the dry eye state in patients with secondary Sjogren's
      syndrome. The study was a randomized, double-masked, placebo-controlled trial.
      Thirty eyes of 15 patients were randomized to undergo treatment with topical
      cyclosporin in olive oil and 30 eyes of the other 15 patients received a placebo,
      which was the sterile olive oil used as a vehicle for the cyclosporin. The effect
      of the 2-month long treatment with either medication on the status of the dry eye
      state was measured by Schirmer-I test, tear film break-up time and rose bengal
      staining. There was a significant increase in the break-up time and a significant
      decrease in rose bengal staining score between the cyclosporin and control groups
      at the end of the 2-month study period (p < 0.01). Schirmer-I test remained
      unaffected (p > 0.05). These results probably indicate that topical cyclosporin
      modulates the goblet cell function in secondary Sjogren's associated
      keratoconjunctivitis sicca and through this mucus enhancing action or some other
      mechanism not yet known, helps to maintain the structural integrity of the
      epithelium.

PMID- 7825409
TI  - Changing indications for penetrating keratoplasty.
AB  - The indications for penetrating keratoplasty have changed over the past several
      years. One hundred and eighty cases of penetrating keratoplasty performed in the
      Department of Ophthalmology, Naestved Centralsygehus, Denmark, from January 1984
      to December 1993, were analysed. Overall pseudophakic bullous keratopathy was the
      most common indication for penetrating keratoplasty (28.3%). This was followed by
      keratitis (13.9%), Fuchs' dystrophy (13.9%), regraft (11.1%), aphakic bullous
      keratopathy (10.0%) and keratoconus (6.7%). Pseudophakic bullous keratopathy was
      the most common indication for penetrating keratoplasty in 1989 and in each year
      from 1991 to 1993. Before 1989 the most common indications were keratitis (18.0%)
      and aphakic bullous keratopathy (14.8%). The emergence of pseudophakic bullous
      keratopathy, as the most common indication for penetrating keratoplasty,
      correlates well with the dramatic increase in the number of cataract extractions
      with intraocular lens implantation performed since the early 1980s. Especially
      semiflexible, closed-loop anterior chamber lenses used in our department in the
      early years of the period, have been the cause of subsequent corneal edema.

PMID- 7825410
TI  - The effect of ultraviolet-B irradiation on the cell shedding rate of the corneal
      epithelium.
AB  - In this study cell shedding rates of the corneal epithelium were determined in
      vitro following a single suprathreshold dose of ultraviolet-B irradiation. Rabbit
      corneas were excised and superfused in pairs. The epithelial and endothelial
      surfaces were bathed with solutions containing essential ions and adjusted to
      appropriate pH and osmolality. One cornea in each pair was irradiated, while the
      other cornea served as a control. Shed cells were periodically collected from the
      corneal surface and the shedding rate determined by counting the number of cells
      in a 50 min time period. Following a latent period of about 3 h, the epithelial
      shedding rate accelerated, and remained elevated for at least 8 h after
      irradiation. This result suggests that suprathreshold doses of ultraviolet-B
      irradiation disrupt the normal orderly cell shedding process and homeostatic
      equilibrium of the corneal epithelium. The elevated cell shedding rate exposes
      subsurface nerve endings and causes the characteristic pain of photokeratitis.

PMID- 7825411
TI  - Photorefractive keratectomy for low myopia at 5 mm treatment diameter. A
      comparison of two excimer lasers.
AB  - The aim of the study was to evaluate the algorithm and surgical performance of
      two excimer lasers, the Summit Excimed 200 LA and the VISX 20/20, by assessing
      visual outcome parameters such as visual acuity and contrast sensitivity, and
      subjectively estimating dark vision performance. Furthermore, refractive results
      and centration of the surgically ablated area were assessed. Twenty patients were
      included in each group. The indications were myopia between -2 to -5 diopters
      allowing up to -0.75 diopters astigmatism. The treatment diameter was 5 mm. The
      postoperative treatment was topical dexamethasone for 3 months. The follow-up
      time was 12 months. The results showed a median refraction +/- 0.0 D in the
      Summit group and -0.5 D in the VISX group 12 months postoperatively. The
      uncorrected visual acuity was 0.5 (20/40) or better for 100% of the Summit
      treated eyes, whereas 85% of the VISX treated eyes achieved 0.5 (20/40) or
      better. The other visual qualities as contrast sensitivity, dark vision and
      centration of the ablation zone were the same in both groups. The slightly more
      myopic outcome of the VISX laser explains the poorer average uncorrected visual
      acuity in this group. We have, as a result of the refractive results, changed our
      algorithm in the VISX machine to achieve emmetropia. It is our experience that
      one should try to reach emmetropia in this young population.

PMID- 7825412
TI  - Phototherapeutic keratectomy in herpes simplex keratitis. Clinical results in 20
      patients.
AB  - Twenty eyes in 20 patients with herpetic keratitis were treated with excimer
      laser photoablation. Sixteen eyes underwent phototherapeutic keratectomy because
      of scars and surface irregularities, with the goal to improve vision and 1 eye
      for cosmetic reasons. Two eyes had slight scars but were treated because of a
      refractive error (PRK). One eye had a metaherpetic ulcer where the wound surface
      was ablated with the intention to improve healing. Twelve of the 16 eyes showed
      improved visual acuity of 2 lines or more on the Snellen chart. The refractive
      outcome was acceptable in the 2 PRK eyes. The cosmetic result was good and the
      metaherpetic wound epithelialized within 3 weeks. Of the 20 patients 5 had 1 or
      more recurrences during the 16.8 months of follow-up. In the 17 months preceding
      the laser surgery 9 eyes had 1 or more recurrences. Three of these eyes still
      showed improved vision. Phototherapeutic excimer laser surgery is advantageous in
      selected cases and should be considered before corneal grafting. The procedure
      does not seem to increase the incidence of recurrences.

PMID- 7825413
TI  - Treatment of recurrent corneal erosions with the excimer laser.
AB  - Seventy-six patients with recurrent corneal erosions resistant to conventional
      therapy with ointment, abrasion or contact lenses were treated with the excimer
      laser. The patients were treated in 3 different ways; ablation of 3 or 5 microns
      after epithelial removal, or ablation of 20 microns directly on the epithelium.
      Twenty out of the 76 treated eyes showed recurrences. Thirty-five of the patients
      had no symptoms after treatment and 21 patients had minor symptoms. The 3
      different treatment modes were equally successful in the present study.

PMID- 7825414
TI  - Transverse keratotomy in postkeratoplasty astigmatism.
AB  - Transverse relaxing incisions were made in 12 eyes with a mean corneal
      astigmatism of 10.7D following penetrating keratoplasty. A few days later the
      mean graft astigmatism had been reduced to 5.5D (p = 0.0022), the reduction being
      significantly correlated to the degree of astigmatism before the keratotomy was
      done (p = 0.0044). Thereafter the corneal contour remained fairly stable through
      a mean follow-up period of 28.1 months, although a tendency towards a further
      reduction of the astigmatism was indicated. The mean corrected visual acuity
      improved from 0.5 before the keratotomy to 0.7 at the last control visit (p =
      0.0117).

PMID- 7825415
TI  - Adult-onset myopia and occupation.
AB  - Eleven female textile workers, all carrying out quality control on textiles
      (close-working distance of 30 cm), were investigated with a view to refractive
      status. Eleven women in the same factory having other working tasks (office,
      sale, production) were used as a control group after being matched regarding age
      and education. Ninety percent of the close workers and 0% of the controls turned
      out to be myopic, and 80% of the close workers had no need for minus glasses
      before the age of 20 years. The refraction (in cycloplegia) was -2.56 (cases) vs
      +1.19 (controls). No deviation was observed concerning keratometry, anterior
      chamber depth and lens thickness. The axial length, however, was 24.36 mm and
      22.72 mm, respectively.

PMID- 7825416
TI  - Relationship of eye movement to computed tomographic findings in patients with
      Graves' ophthalmopathy.
AB  - To elucidate the relationship between eye movement and computed tomographic
      findings, 101 patients with Graves' ophthalmology were studied. Eye movements
      were scaled 0 to 3 according to movability. Extraocular muscle width and area
      were calculated from the largest portion of each muscle from the orbital coronal
      CT sections. Muscle widths were measured manually and muscle areas were
      calculated by a digitizer. The width and area of each rectus muscle were
      significantly correlated with limitation of eye movement. The muscle widths and
      areas were also significantly correlated to each other (r = 0.91 to 0.77, p <
      0.001). Limitations of supraduction and abduction from enlargement of the
      inferior and medial rectus muscles were the most common clinical findings (46.5%
      and 39.6%, respectively). In conclusion, this study establishes a relationship
      between limitation of eye movement and extraocular muscle enlargement.
      Calculation of the width from the largest portion of the muscle manually from
      orbital coronal section is a simple method for clinical assessment of the
      severity of extraocular muscle involvement.

PMID- 7825417
TI  - Cataract surgery with implantation of IOL in patients with uveitis.
AB  - Traditionally, IOL implantation in eyes with uveitis has not been recommended. In
      the present study 31 eyes with uveitis which underwent extracapsular cataract
      extraction or phacoemulsification with IOL implantation, are compared to a
      reference group consisting of 930 eyes. There was increased postoperative
      inflammation in 29% in the uveitis group, compared to 5.9% in the reference
      group. The rate of per- and postoperative complications was slightly elevated in
      the group with uveitis. Corrected visual acuity of 5/8.5 or better was achieved
      in 58.1%. The major obstacle to good visual acuity postoperatively, was macular
      pathology.

PMID- 7825418
TI  - A study of the axis of orientation of residual astigmatism.
AB  - The aim of this study was to determine the axis of orientation of residual
      astigmatism in a sample of human eyes applying the principle of astigmatic
      decomposition. Calculations were carried out on keratoscopic and refractive data
      collected from the right and left eyes of 70 subjects (37 male and 33 female
      students) of mixed race (including 25 Asians and 43 Caucasians). No statistically
      significant difference was found for mean levels of residual astigmatism measured
      in the right (0.46 DC x 98.2 degrees) and left (0.50 DC x 99.4 degrees) eyes.
      Residual astigmatism was predominantly against-the-rule (83% of right eyes and
      66% of left eyes) and was within +/- 20 degrees of being perpendicularly disposed
      relative to the corneal astigmatic power axis in two thirds of the eyes measured.
      No statistically significant differences were found for either gender or race.

PMID- 7825419
TI  - The relationship between cataract and climatic droplet keratopathy in Mongolia.
AB  - This study evaluated the association between cataract, the commonest single
      blinding disorder worldwide, and climatic droplet keratopathy which was taken as
      an indicator of high exposure to ultraviolet sunlight. A sample of 4344 persons
      from rural Mongolia (1991-92) provided 8634 eyes for analysis of the relationship
      between cataract and climatic droplet keratopathy. Right and left eyes were
      combined (paired into matched sets), and analysed using a random-effects
      regression model. The results indicated an inverse association between cataract
      and climatic droplet keratopathy in person aged 55 years or older, whereby eyes
      with more advanced climatic droplet keratopathy had lower prevalence of cataract
      (age-adjusted odds ratio 0.53, p = 0.047). In the younger group of persons aged
      40-54 years, the reverse was found, whereby cataract prevalence was higher in
      eyes that have climatic droplet keratopathy (age-adjusted odds ratio 13.19, p =
      0.046). However, only a small proportion (4%) of all the cataracts occurred in
      this younger age stratum where the prevalence of cataract was 0.5%, compared to
      prevalence of 17% in eyes of persons aged 55 years or older. These findings cast
      further doubts upon the current thesis that lifetime exposure to high levels of
      ultraviolet sunlight is a major cause of cataract in developing countries.

PMID- 7825420
TI  - Efficacy and safety of timolol/pilocarpine combination drops in glaucoma
      patients.
AB  - The aim of this randomized, double-blind study with two parallel groups was to
      examine the safety, efficacy and tolerability of two combination eye drops
      containing 0.5% timolol and 2% pilocarpine (Fotil, Leiras, Finland, and Timpilo,
      MSD, USA) in patients with glaucoma or ocular hypertension. Efficacy was
      determined based on daytime intraocular pressure curve and safety by examining
      visual fields, visual acuity, optic discs, by determining blood pressure and
      pulse rate, and by performing Schirmer and fluorescein tests. A total of 89
      patients were enrolled, and 71 completed the 10-week treatment period. This study
      showed that the two combinations of 0.5% timolol maleate and 2% pilocarpine HCl
      compared in this study were equally effective in reducing intraocular pressure.
      The decrease in mean daily intraocular pressure from 0 to 10 weeks was 7.48 mmHg
      for Fotil, and 6.31 for Timpilo. The mean decrease in mean daily intraocular
      pressure was 29.3% for Fotil, and 26.0% for Timpilo. No significant differences
      were found between the groups. Adverse event were reported by 70 out of 89
      patients by the end of 2 weeks, but were severe enough only in 11 for the
      treatment to be discontinued. In all others, adverse events were of transient
      nature and considered mild. In general, adverse events were similar in both study
      groups. However, burning was more common in patients on Fotil, and blurring of
      vision and light sensitivity were more common in patients on Timpilo. In patients
      with no contraindication to beta-blockers, these drugs appeared to be
      safe.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7825421
TI  - Uveitis survey at the University Eye Clinic in Turku.
AB  - We conducted a retrospective analysis of 1122 patients with endogenous uveitis
      treated at the University Eye Clinic in Turku during the years 1980-1982 and
      1988. Of the 1122 patients 568 were men and 554 women; 1034 (92.2%) had anterior
      uveitis, 15 (1.3%) intermediate uveitis, 64 (5.7%) posterior uveitis and 9(0.8%)
      panuveitis; 867 (77.3%) were unilateral and 255 bilateral; 789 of 1067 cases
      (73.9%) were of sudden onset and 278 of insidious onset; 808 of 1102 cases
      (73.3%) were of short duration and 294 of long duration; and 519 (46.3%) single
      and 603 repeated. In this study uveitis occurred significantly more often (44.2%)
      in the age group 20-39 years than in other age groups (p < 0.00001). Anterior and
      posterior uveitis were more often unilateral than bilateral (p < 0.0005) and of
      sudden onset than of insidious onset (p < 0.00008). Acute anterior uveitis was
      the most common uveitic entity and accounted for 745 cases (66.4%). Acute
      anterior uveitis associated with ankylosing spondylitis was the single most
      frequently seen diagnostic group including 144 cases (12.8%) with a statistically
      significant male predominance (p < 0.00001).

PMID- 7825422
TI  - Potassium iodate retinopathy.
AB  - A case of potassium iodate toxicity in a 22-year-old man was reported. After
      taking a solution of highly concentrated potassium iodate, the patient developed
      nausea, vomiting, diarrhea and blurred vision. The visual acuity was hand motion
      in both eyes. The funduscopic examination showed retinal edema with subsequent
      pigmentary change at the macula and retinal pigment clumping resembling retinitis
      pigmentosa. The fundus fluorescein angiography and electrophysiologic studies
      showed degenerative changes of the retinal pigment epithelium and photoreceptor
      cells.

PMID- 7825423
TI  - Orbital myositis secondary to systemic lupus erythematosus.
AB  - A 41-year-old woman presented to our department with a 2-year history of
      unilateral painful swelling of the right eye. Clinical and laboratory evaluation
      ruled out endocrine, infectious and neoplastic disorders, and suggested the
      diagnosis of systemic lupus erythematosus. Echographic examination of the orbit
      and CT-scan revealed enlargement of the lateral and inferior rectus muscles at
      the right side, and enlarged medical rectus muscle at the left side. Despite the
      involvement of the extraocular muscles the patient did not have any ocular
      motility defects nor diplopia. The condition responded rapidly to systemic
      corticosteroids associated with immunosuppressive agents.

PMID- 7825424
TI  - Gas gangrene panophthalmitis. A case from Greenland.
AB  - A case of clostridium perfringens gas gangrene panophthalmitis developed after a
      penetrating eye injury. The affected eye became amaurotic, but the
      panophthalmitis was controlled by minimal surgical debridement and systemic
      antibiotic therapy with penicillin, fucidic acid and metronidazole. Elective
      enucleation was performed 15 days after the trauma for cosmetic reasons. The
      enucleated eye was examined histopathologically and showed massive retinal
      necrosis but no signs of bacteriae.

PMID- 7825425
TI  - Can posturography contribute to the diagnosis of vertigo in patients where other
      tests fail to do so?
AB  - In this study, patients showing abnormal posturographic results in a test
      configuration upon examination of the visuo-proprioceptive-vestibular interaction
      (Static Posturography type III, SPGIII) are reviewed. Group I (n = 81) comprised
      patients for whom no clear diagnosis could be obtained (neither central nor
      peripheral) and with rather atypical complaints. Group II (n = 77) comprised
      patients in whom a well-defined peripheral disorder could be found (typical
      provoked vertigo as BPPV (n = 30) and Meniere's disease (n = 30)). Group I
      consisted of s subgroup Ia, including patients with a complete negative classical
      examination (n = 32), a subgroup Ib with patients showing minor central signs (n
      = 28), and subgroup Ic comprising patients with slight peripheral indications (n
      = 21). The findings in SPGIII were compared between these two groups and are
      discussed in the light of earlier experience with such data in typical peripheral
      vestibular disorders. Similar sensory interaction patterns were found in both
      groups, with only small differences between them, suggesting that in some of
      these cases, especially in subgroups Ia and Ic, vestibular disturbance might be
      present, which would not have been sufficiently and clearly revealed by the
      classical tests. Especially the negative effects, i.e. when the withdrawal of a
      sensory input improved stability instead of aggravating it, which is the opposite
      to what should be expected, suggest that the other sensory inputs, vision and
      proprioception, play a role in the definition of the posturographic results in
      typical vestibular disorders as well as in diagnosis.

PMID- 7825426
TI  - Head position dependent adjustment of the three-dimensional human vestibuloocular
      reflex.
AB  - We studied the influence of static head position relative to the rotation axis on
      the three-dimensional (3-D) vestibuloocular reflex (VOR). By means of a 3-D
      rotating chair and a 3-D magnetic search-coil system, eye movements were recorded
      in 6 normal human subjects during sinusoidal rotation about an earth-vertical
      axis (yaw) with the head positioned at different pitch angles and about an earth
      horizontal axis (pitch) with the head positioned at different yaw angles. We
      confirmed that torsional VOR gain is about 2/3 of horizontal and vertical VOR
      gain leading to non-collinear axes of eye and head rotation whenever torsional
      head movement components were present with eye movement axes tilting away from
      the torsional direction. Despite this non-collinearity of stimulus and eye
      movement rotation axes there was close to perfect adjustment of the different VOR
      components depending on the angle between gaze direction and stimulation axis,
      indicating a vectorial summation of gains obtained for rotations in the major
      body axes (roll, pitch and yaw). The horizontal and vertical eye movement
      components followed a cosine function of the angle between the plane of rotation
      and gaze direction. The torsional component followed a sine function.

PMID- 7825427
TI  - Discrimination between patients with acoustic neuroma and with peripheral
      vestibular lesion by human posture dynamics.
AB  - A group of normal subjects (n = 17) was compared with two groups of patients,
      either with vestibular neuritis (n = 18) or with acoustic neuroma (n = 35) by
      means of posturography when stance was perturbed with vibrators attached to the
      calf muscles. Dynamic control of human posture was quantified by means of system
      identification, and the characteristic parameters of swiftness, stiffness, and
      damping of a transfer function from vibration to force platform response were
      used for further comparison. Fisher linear discriminant analysis was used to
      distinguish sets of parameters characteristic of each disease. Hence it was
      possible to distinguish the vestibular neuritis group both from the normal group
      (p < 0.01), and from the patients with acoustic neuroma (p < 0.001). The normal
      group was characterized by a different postural performance, with higher
      swiftness and stability parameters (stiffness, damping) than those of the patient
      groups. These findings indicate that there are differences in the dynamic control
      of posture between the two patient categories, which may require the development
      of differentiated rehabilitation programs.

PMID- 7825429
TI  - Immediate and long-term effects of daily glycerol administration on guinea pig
      hydropic ears.
AB  - Oral administration of glycerol at 0.5 g/kg and 1.0 g/kg body weight in the
      guinea pig with experimentally induced hydrops provoked no obvious modifications
      of the CAP audiogram within a 3-h recording session. Daily administration of
      glycerol at the same dose level during a 4-month period did not modify the
      deterioration of CAP thresholds although some limited beneficial effect was
      detected for some animals after 8 weeks of treatment.

PMID- 7825428
TI  - Functional maturation of the medial efferent olivocochlear system in human
      neonates.
AB  - The effect of contralateral acoustic stimulation on transient evoked otoacoustic
      emissions (TEOAE) was used to investigate the functional maturity of the medial
      efferent olivocochlear system in full term neonates and a 6-week-old baby. The
      technique used was to record the TEOAE alternately with and without contralateral
      noise. The result was a reduction in TEOAE amplitude and latency. This was best
      illustrated with a difference waveform obtained from the subtraction of the TEOAE
      waveform recorded with contralateral noise, from the waveform recorded without
      contralateral noise. All the full term neonates and also the 6-week-old baby
      showed significant effects indicating functional maturity of the medial
      olivocochlear system.

PMID- 7825430
TI  - Evoked potentials from the auditory nerve following sinusoidal electrical
      stimulation of the cochlea: new possibilities for preoperative testing in
      cochlear-implant candidates?
AB  - To predict the possible benefit of a cochlear implant to a patient, the clinician
      requires a reliable objective method to monitor the presence of surviving fibres
      in the 8th nerve. The subjective promontory test and the evaluation of
      electrically evoked brainstem potentials are not adequate. An electrical stimulus
      artefact interferes badly with the potential recorded, but with electrical
      sinusoidal stimulation this stimulus artefact can be suppressed. The highly
      synchronous excitation of the auditory nerve fibres results in compound action
      potentials that can be recorded from the round window. The present animal
      experiments show that the method proposed is effective. Clinical tests are
      suggested.

PMID- 7825432
TI  - Intracellular calcium changes by hyposmotic activation of cochlear outer hair
      cells in the guinea pig.
AB  - During continued exposure to a hypotonic solution, isolated outer hair cells
      (OHCs) from the guinea pig cochlea showed a regulatory volume decrease (RVD)
      after initial cell swelling. In the absence of extracellular Ca2+, RVD was
      significantly inhibited. Using Ca(2+)-sensitive dye fura-2, accompanying changes
      of the intracellular Ca2+ concentrations ([Ca2+]i) of OHC were investigated.
      Hyposmotic activation resulted in a [Ca2+]i increase associated with cell
      shortening and swelling. In a Ca(2+)-free solution, [Ca2+]i was not significantly
      increased during hyposmotic activation although shortening and swelling of the
      OHC was observed. These results suggest that the increase in [Ca2+]i during
      hyposmotic activation is mainly based on an influx or extracellular Ca2+ which
      precedes the RVD.

PMID- 7825431
TI  - Electromagnetic stimulation of the auditory system of deaf patients.
AB  - Electromagnetically induced auditory perception was investigated in 18 deaf
      patients who were candidates for cochlear implants. In the extracranial magnetic
      stimulation (EMS) procedure, patients were stimulated with time-varying magnetic
      field brief pulses from a coil positioned at the i) auricle, ii) the mastoid, and
      iii) the temporal lobe area. EMS elicited auditory sensations in 26 ears (of 14
      patients/subjects). The lowest threshold of auditory sensation (TAS) was found to
      be at the 20% EMS level, with a range of 20-50% of the maximum level (2.0 Tesla),
      and approximately equal sensitivity in each coil position. Eleven of the subjects
      hearing EMS-induced sound perceived changes in pitch while 6 heard "clicks" or
      clicks and tones. Spearman Rho correlation analysis showed a mild negative
      correlation between the EMS/TAS and the pre-implant FFA, best tone threshold
      (BTT), and direct promontorial electrical stimulation (ES) thresholds at 250 Hz
      and 500 Hz. No correlation was found between EMS or ES and performance on the pre
      implant or post-implant psychacoustic tests (MAC VIII or 3-Digit speech tests) or
      the measurements of the thickness of cutaneous and osseous tissue from the
      stimulation sites at the mastoid and ear canal to the cochlear and 8th nerve. A
      fair positive correlation was found between the EMS/TAS and the post-implant (6
      months) ES threshold when the electrodes allocated the 500 Hz frequency range
      were stimulated. A mild positive correlation between the pre-cochlear-implant
      promontorial electrical stimulation (ES) at 250 Hz and the four frequency tone
      average (FFA: 0.5, 1, 2, 4 kHz) was also found.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7825433
TI  - SEM observation and GABA immunoreactivity of human embryonic organ of Corti
      tissue culture.
AB  - Scanning electronic microscopy (SEM) observation and GABA immunoreactivity of the
      tissue culture of 6 human embryonic organs of Corti are reported. The normal
      structural appearance of the hair cells and the facts that there were no bulging
      of cuticular plates, and cytoplasmic protrusion proved that the hair cells were
      healthy. After GABA immunostaining, radial bundles, innerspiral bundles, and the
      ending of inner and outer hair cell regions displayed typical GABA-positive
      reactivity. The results indicate that the human embryonic organ of Corti is well
      developed differentiated, and mature at 19 gestational weeks and can continue to
      grow and differentiate in vitro. The study offers an ideal and important
      biological model for further research into the human ear.

PMID- 7825434
TI  - Gap junction systems in the rat vestibular labyrinth: immunohistochemical and
      ultrastructural analysis.
AB  - The distribution of gap junctions within the vestibular labyrinth was
      investigated using immunohistochemistry and transmission electron microscopy.
      Connexin26-like immunoreactivity was observed among supporting cells in each
      vestibular sensory epithelium. Reaction product was also present in the
      transitional epithelium of each vestibular endorgan and in the planum semilunatum
      of crista ampullaris. No connexin26-like immunoreactivity was observed among thin
      wall epithelial cells or among vestibular dark cells. In addition, fibrocytes
      within vestibular connective tissue were positively immunostained. Reaction
      product was also detected in the melanocyte area just beneath dark cells.
      Ultrastructural observations indicated that a gap junction network of vestibular
      supporting cells extends to the transitional epithelium and planum semilunatum
      and forms an isolated epithelial cell gap junction system in each vestibular
      endorgan. In contrast, no gap junctions were found among wall epithelial cells or
      among dark cells. Fibrocytes and melanocytes were coupled by gap junctions and
      belong to the connective tissue cell gap junction system, which is continuous
      throughout the vestibular system and the cochlea. The possible functional
      significance of these gap junction systems is discussed.

PMID- 7825435
TI  - Adrenergic innervation of the human endolymphatic sac.
AB  - Adrenergic innervation of the human endolymphatic sac (ES) has not been verified
      previously. To investigate this question a sensitive histofluorescence method for
      visualization of catecholamines and serotonin, using a solution composed of
      sucrose-potassium phosphate-glyoxylic acid (SPG) in cryostat sections, was
      employed. Three human ES specimens were obtained during surgery for acoustic
      neuroma. Distinct fluorescence in the subepithelial tissue, indicating the
      presence of monoaminergic neurones and their axonal varicosities, was observed.
      SPG-positive terminal nerve fibres around small ES capillaries and
      subendothelially were also seen. Like the effects of sympathetic stimulation
      elsewhere in the human body, the ES might respond to such stimulation with, for
      example, vasoconstriction and increased transepithelial water transport. Since
      the ES is thought to be responsible for maintaining inner ear fluid homeostasis,
      adrenergic influence could be important for it to function properly.

PMID- 7825436
TI  - Experimental cholesteatomas arising from autologous free skin grafting in the
      middle ear cavity.
AB  - An autologous free skin graft taken from the upper or the lower external ear
      canal or the auricle was implanted in the otic bulla of 28 guinea pigs. An
      epidermal cyst simulating middle ear cholesteatoma was successfully produced in
      25 (89.3%) animals 8 weeks after grafting. Using this model, the histological
      reaction of middle ear granulation tissue to the debris was studied. Cysts
      originated from the auricular skin showed the strongest activity with regard to
      growth rate, amount of debris produced, and inflammatory reaction to the exposed
      debris. We conclude that the exposed debris plays an important role in chronic
      granulomatous inflammation in association with cholesteatoma.

PMID- 7825437
TI  - Effect of growth factors on cell proliferation by human nasal septal chondrocytes
      cultured in monolayer.
AB  - In the field of reconstructive surgery, autologous cartilage grafting is commonly
      performed to reconstruct skeletal defects. Because of the limited supply of fresh
      autologous cartilage many investigators concentrate on in vitro production of
      cartilage tissue. Several growth factors regulate the metabolism and activation
      of cartilage cells. In order to enhance the culture conditions for cartilage
      cells, the aim of our investigations was to characterize the influence of
      transforming growth factor (TGF)-beta, epidermal growth factor (EGF) and basic
      fibroblast growth factor (bFGF) on the proliferation of differentiated human
      nasal septal chondrocytes. The isolated cells were cultured in monolayer using
      DMEM with and without 10% FCS. The cell proliferation was assessed using
      tritiated thymidine. We measured an increase of the proliferation rates when the
      different growth factors were added. The most important stimulatory effect was
      due to bFGF and the less to EGF. If all growth factors were added together a
      fivefold increase in the proliferative activity of the cells was achieved. The
      effects were further enhanced by factors present in fetal calf serum. We conclude
      that the culture conditions for cell expansion for cartilage engineering can be
      optimized employing growth factors.

PMID- 7825438
TI  - Endothelin-induced vasoconstriction in rabbit nasal mucosa.
AB  - Nasal blood flow is finely regulated by local release of neurotransmitters,
      neuropeptides and other bioactive molecules acting via paracrine mechanisms. We
      have investigated the effects of endothelin-1 (ET-1), a potent vasoconstrictor
      peptide, on the blood perfusion of rabbit nasal mucosa by laser Doppler
      flowmetry. After injection with ET-1, a potent and prolonged nasal
      vasoconstriction was observed. ET-immunoreactivity has previously been detected
      in nasal tissues and it is therefore suggested that ET-1 may participate in the
      regulation of nasal blood flow via paracrine mechanisms.

PMID- 7825439
TI  - Nitrogen dioxide-induced eosinophilia and mucosal injury in the nose of the
      guinea pig.
AB  - Nitrogen dioxide exposure-induced mucosal pathology of the guinea pig nose was
      studied. Guinea pigs were exposed to 3 ppm or 9 ppm of nitrogen dioxide for 6 h a
      day, 6 times weekly for 2 weeks, and sacrificed 24 h after the final exposure.
      Exposure to 3 ppm of nitrogen dioxide resulted in decreased ciliary activity and
      slight eosinophil accumulation on the epithelium and submucosal layer. More
      serious pathologies were observed in the nose of guinea pigs exposed to 9 ppm of
      nitrogen dioxide, including a more prominent eosinophil influx to the epithelium
      and epithelial injury due to activation of eosinophils. Epithelial damage induced
      by nitrogen dioxide could lead to hyperresponsiveness and may result in a
      prolonged allergic inflammation. Our study suggests that environmental nitrogen
      dioxide may contribute to hyperresponsiveness and thus be involved in the
      increased morbidity of allergic rhinitis.

PMID- 7825440
TI  - Concentrations of chemical mediators in nasal secretions of patients with hay
      fever during natural allergen exposure.
AB  - By using the microsuction technique, quantitative determination of the chemical
      mediators in nasal secretions was performed in 40 patients with seasonal allergic
      rhinitis during the pollen season. The aim of this study was to investigate the
      actual concentrations of these important mediators in nasal secretions during
      natural allergen exposure so as to better understand the pathophysiology of
      allergic rhinitis. The median concentrations of four mediators, were histamine:
      51.5 ng/g (range: 4-146 ng/g); tryptase: 0 (range: 0-84 microU/g); leukotriene C4
      (LTC4): 23 ng/g (range: 11-77 ng/g); and eosinophil cationic protein (ECP): 410
      ng/g (range: 6-2380 ng/g). The authors compared these concentrations with those
      of the same mediator found in a previous study of seasonal allergic rhinitis
      patients after nasal challenge outside the pollen season. The present study
      demonstrates that during the season allergic rhinitis reflects a chronic state of
      allergic inflammation of the nasal mucosa involving various inflammatory
      mediators induced by one or more episodes of early type allergic reaction.

PMID- 7825441
TI  - Clinical course of patients with primary nasal polyps.
AB  - A follow-up study on 180 patients treated for the first time for nasal polyps was
      performed. The follow-up period was from 1 to 8 years with a median of 57 months.
      The majority of patients had postoperative topical steroid treatment. 65.6% of
      patients had one polypectomy, 17.8% had two polypectomies, 10% had 3, 2.8% had 4,
      and 3.9% of patients had 5-10 polypectomies performed during the follow-up
      period. Patients without asthma, acute recurrent or chronic sinusitis,
      acetylsalicylic acid intolerance, or allergy had fewer polypectomies and less
      topical steroid treatment than patients with these characteristics. The
      recurrence profile between the first and second polypectomy described with the
      life-table method showed a slow decline in the number of patients with only one
      polypectomy. The time span needed before significant clinical symptoms occurred
      after the first polypectomy indicates that not all primary polyp patients are
      prone to recurrence. Nasal polyps is probably a manifestation of different
      clinical and aetio-pathogenetic entities. Further identification of such entities
      is needed to improve treatment strategy.

PMID- 7825442
TI  - Calcitonin gene-related peptide-like immunoreactive motoneurons innervating the
      canine inferior pharyngeal constrictor muscle.
AB  - The percentage of the calcitonin gene-related peptide-immunoreactive motoneurons
      (Mn) in the nucleus ambiguus (NA) innervating the canine inferior pharyngeal
      constrictor muscle was examined using the cholera toxin B subunit-gold (CTBG) as
      a retrograde tracer and by immunohistochemistry. Labeled neurons with CTBG (CTBG
      MNs) from the thyropharyngeal muscle (TP) were located in the dorsomedial
      division of the rostral part of the NA and the average percentage of neurons with
      CGRP immunoreactivity was 70.3%. CTBG MNs from the cricopharyngeal muscle (CP)
      were located in the dorsal division of the rostral part of the NA and the average
      percentage of neurons with CGRP immunoreactivity was 21.2%. This low percentage
      of CGRP immunoreactivity is noteworthy and supports the idea that the CP is a
      particular striated muscle in function and innervation manner.

PMID- 7825443
TI  - Predictive value of Muller maneuver, cephalometry and clinical features for the
      outcome of uvulopalatopharyngoplasty. Evaluation of predictive factors using
      discriminant analysis in 30 sleep apnea patients.
AB  - The success rate of uvulopalatopharyngoplasty (UPPP) in the treatment of
      obstructive sleep apnea is generally only 50-60%. In order to improve this,
      various predictive factors for the outcome of UPPP were studied, including the
      Muller maneuver and cephalometry. Thirty unselected consecutive patients with
      obstructive sleep apnea (median apnea index (AI) 26 apneas/h, range 5-78)
      underwent UPPP with standard tonsillectomy except in the case of small tonsils
      and using CO2 laser for the palatal resection. Polysomnographic control 5 months
      after surgery showed that 63% of all patients had obtained a reduction in AI > or
      = 50% including an AI < 20 after surgery. Tonsillectomy had no influence on the
      outcome. Further, the Muller maneuver did not predict the outcome, whereas
      cephalometry proved to be of good predictive value. Lowered position of the hyoid
      bone, increased cranio-cervical angle and shortening of the maxilla length were
      significantly associated with poor results of UPPP, as were overweight, narrowing
      of the hypopharynx, the severity of sleep apnea, and hypersomnia. However, in a
      discriminant analysis containing all these variables, the three cephalometric
      measurements together with hypersomnia were most closely associated with the
      outcome of UPPP. A predictive model containing these four variables could
      correctly classify 83% of the patients in the present study. The model had a
      false positive rate of 7% in predicting a successful outcome. This indicates that
      cephalometry is mandatory in the selection of UPPP candidates and that a
      predictive model containing some or all of the four variables may substantially
      improve the success rate.

PMID- 7825444
TI  - Epstein-Barr virus (EBV) infection and undifferentiated carcinoma of the parotid
      gland in Caucasian patients.
AB  - The Epstein-Barr virus (EBV) has been detected in certain types of lymphoma and
      some epithelial neoplasms such as nasopharyngeal lymphoepithelioma and occasional
      undifferentiated carcinomas in several organs including the salivary glands.
      However, clonal EBV genomes have been detected in undifferentiated carcinomas of
      the parotid gland exclusively in Alaskan natives and Eskimos, both groups being
      at the highest risk for nasopharyngeal carcinoma. The authors investigated the
      possibility that EBV may be present in undifferentiated parotid carcinomas in
      Caucasian subjects. To test this hypothesis, in situ hybridization (ISH)
      technique with biotinylated EBV-DNA probes was utilized on routinely processed,
      paraffin-embedded tissues from 7 cases of undifferentiated carcinomas of the
      parotid gland. EBV genomes were demonstrated in the cytoplasm of tumor cells from
      3 out of 7 specimens tested. Surprisingly, EBV genomes were found in 3 out of 5
      (60%) undifferentiated carcinomas that had developed in patients with a history
      of a long-persisting asymptomatic parotid mass, which had suddenly increased in
      size. Conversely, none of the undifferentiated carcinomas with continuous and
      rapid growth studied was found to be positive for EBV-DNA by ISH technique. Taken
      together, these data might suggest a possible role of EBV in the transformation
      of benign parotid gland lesions into malignant and aggressive undifferentiated
      carcinoma of the parotid gland, the so-called carcinoma expleomorphic adenoma.

PMID- 7825445
TI  - Effects of human neonatal serum on DNA synthesis in suckling and adult rat
      hepatocytes in primary culture.
AB  - The effect of human neonatal serum on DNA synthesis in suckling and adult rat
      hepatocytes in primary culture was investigated to characterize growth regulating
      factors of the liver in neonates and to confirm whether the stimulatory factor is
      human hepatocyte growth factor (hHGF). Neonatal serum stimulated DNA synthesis of
      both adult and suckling rat hepatocytes. The stimulatory effect was dose
      dependent up to 20% in volume. The molecular weight of the stimulatory substance
      in neonatal serum was between 12,500 and 25,000, as estimated by gel filtration.
      Its activity was stable after heating at 56 degrees C for 20 min, but was lost
      after heating at 90 degrees C for 30 s, and easily passed through S- or heparin
      Sepharose columns. The concentration of hHGF quantified by ELISA was too low to
      stimulate DNA synthesis in vitro. Biological and biochemical properties of the
      growth stimulatory activity in neonatal serum differed from that of hHGF. The
      presence of other growth factors in human neonatal serum for suckling and adult
      hepatocytes was suggested.

PMID- 7825446
TI  - Tuberculous meningitis in children.
AB  - Between May 1988 and November 1992 the data from 52 patients with tuberculous
      meningitis (TBM) were noted down for their symptoms and signs, BCG vaccines, PPD
      tests; clinical, laboratory, radiologic and microbiologic findings. These data
      were discussed by means of literature knowledge. Cranial computed tomography (CT)
      demonstrated hydrocephalus (HC) in 98% of the patients. There was a statistically
      significant difference among the clinical stages on admission in respect to
      prognosis (P < 0.05). In addition, there was also a significant relationship
      between prognosis and HC (P < 0.05). However, we did not find any significant
      relationship between parenchymal involvement, basilar meningitis and prognosis (P
      > 0.05).

PMID- 7825447
TI  - The fluctuations of neuron-specific enolase (NSE) levels of cerebrospinal fluid
      during bacterial meningitis: the relationship between the fluctuations of NSE
      levels and neurological complications or outcome.
AB  - Neuron-specific enolase (NSE) is one of the glycolytic enzymes distributed
      exclusively in neurons. It was measured serially in the cerebrospinal fluid (CSF)
      of 10 children with bacterial meningitis during the illness using radio
      immunoassay. The relationship between CSF-NSE levels and neurological
      complications or outcome was examined. CSF-NSE levels were significantly higher
      in the patients with bacterial meningitis than in the patients with the other
      central nervous system (CNS) infectious diseases, suggesting that CNS damage in
      those patients with bacterial meningitis was exacerbated. As CSF-NSE levels
      increased to above 25 ng/mL in the acute phase, all patients except one had
      subdural effusion. In those patients whose CSF-NSE level rose again during the
      illness, CNS complications or sequelae occurred. CSF-NSE may be a useful
      prognostic factor for predicting CNS damage in childhood bacterial meningitis.

PMID- 7825448
TI  - Increased levels of antibodies to food proteins in Down syndrome.
AB  - An increased level of immunoglobulin A (IgA) antibodies to food antigens has been
      found in Down syndrome. Biopsy did not show any anomaly of the gut. Increased IgA
      levels against specific proteins reflect increased transmucosal transport of
      antigens. The antigens presented may be immunogenic peptides or intact antigens.
      In this paper, we wished to exclude an institutional cause such as infections and
      also age differences.

PMID- 7825449
TI  - What are parents of obese children concerned about in their children?
AB  - We retrospectively examined the issues that concern parents of obese children to
      determine the most effective means of motivating them to seek treatment for
      obesity in their children. Children with an obesity index > or = 40%, aged six to
      12 years, were screened in Kagoshima City in 1992. Parents were notified if their
      children needed an evaluation that included a family history and measurements of
      the blood pressure, total cholesterol, high density lipoprotein (HDL)
      cholesterol, atherogenic index (ASI), triglycerides, aspartate aminotransferase
      (AST) and alanine aminotransferase (ALT). Parents were informed of the results of
      the evaluation and invited to attend a lecture on the treatment of obesity in
      children. A total of 378 obese children were evaluated. However, the parents of
      only 39 children attended the lecture. Children whose parents attended had higher
      mean total levels of cholesterol (190 +/- 25 vs 175 +/- 28, P < 0.01) and ASI
      values (3.2 +/- 0.9 vs 2.7 +/- 0.9, P < 0.02) than those whose parents did not
      attend. There were no significant differences in other factors. Only 4.2% of
      parents whose children showed no abnormal values, except for obesity, attended
      the lecture, compared with 20.3% (P < 0.01) or 16.9% (P < 0.05) of parents whose
      children had abnormal levels of cholesterol or abnormal ASI. Parents may be more
      concerned about hypercholesterolemia or arteriosclerosis than obesity per se. We
      should perhaps use the total cholesterol or ASI values, not just the severity of
      obesity, to motivate parents to enter their children into treatment programs for
      obesity.

PMID- 7825450
TI  - A new protocol for the perinatal management of patients with congenital
      diaphragmatic hernia with severe hypoplastic lungs and its clinical application.
AB  - It is prerequisite for the pre-operative management of patients with congenital
      diaphragmatic hernia (CDH) to avoid the factors that increase pulmonary vascular
      resistance, because such patients easily fall into the state of persistent fetal
      circulation (PFC). In this paper, a new protocol is proposed for the perinatal
      management of CDH patients to prevent the PFC which is facilitated by the
      enlargement of hernia and the deviation of mediastinum caused by spontaneous
      breathing just after birth. We also describe the usefulness of this protocol
      based on our experience in which we successfully treated a patient with CDH with
      severe hypoplastic lungs that were diagnosed antenatally by ultrasonographic
      examination. In treating the CDH patient with severe hypoplastic lungs, it is
      effective for the respiratory control and the prevention of PFC to administer
      morphine and pancuronium to the neonate through the umbilical vein before the
      resection of the umbilical cord. In the case of Cesarean section, in addition to
      the direct administration of morphine to the patient, administration of morphine
      to the patient's mother just before the delivery is more effective to prevent
      PFC, which can be easily induced by the initial resuscitation at birth.

PMID- 7825451
TI  - A comparison of left ventricular volumes and regurgitant fraction by Doppler
      echocardiography and angiography in children.
AB  - Regurgitant fraction calculations by echocardiography were compared to
      angiocardiography in 11 patients with mitral regurgitation. Although there was a
      very good correlation when compared with angiocardiography (r = 0.99, SEE: 6.26,
      P < 0.001), two-dimensional echocardiography underestimated left ventricular end
      diastolic volumes (P < 0.05). The mean regurgitant fraction was 36.2 +/- 13.5% by
      echocardiography and 43.6 +/- 15.7% (P < 0.05) by angiography. Most of the
      variability in measuring the regurgitant fraction is attributed to the left
      ventricular volume measurements. In conclusion, regurgitant fraction calculations
      of mitral regurgitation by echocardiography compares favorably to angiography.
      Since the severity of mitral regurgitation is an important determinant of
      prognosis, quantification of the regurgitant fraction may be useful in the long
      term follow-up of those patients.

PMID- 7825452
TI  - Alagille syndrome with a spontaneous appearance of the interlobular bile ducts.
AB  - We report a rare case of a 10 year old girl diagnosed as having Alagille syndrome
      on the basis of a characteristic face, posterior embryotoxon, cholestasis,
      peripheral pulmonary artery stenosis and the absence of interlobular bile ducts
      in a liver biopsy at 1.5 years of age. Since 1.5 years old, she had been in good
      health without medication and the serum biochemical liver function tests
      indicated no progression of cholestasis. A second liver biopsy at 9.5 years of
      age showed normal interlobular bile ducts confirmed by anti-keratin staining at
      each of the five examined portal areas. Alagille syndrome is usually associated
      with the progressive disappearance of interlobular bile ducts. The findings of
      interlobular bile ducts in the second liver biopsy were therefore rare and unique
      to this case.

PMID- 7825453
TI  - New interpretation and management of dry lung syndrome: a case report.
AB  - A premature female infant with life-threatening respiratory distress which was
      diagnosed as 'dry lung syndrome' is reported. The mother had 4 weeks of large
      volume leakage of the amniotic fluid due to premature rupture of the fetal
      membranes (PROM) at 23 weeks' gestation. The infant was born after 27 weeks'
      gestation (birthweight, 1016 g) and was suffering severe respiratory distress.
      Although a chest radiogram and gastric juice microbubble test did not improve the
      possibility of respiratory distress syndrome (RDS), very high ventilator settings
      did not improve her respiratory disorders. Considering the infant's deteriorating
      respiratory status and the prolonged leakage of the amniotic fluid, we suspected
      the presence of pulmonary hypoplasia. Although an attempt at high frequency
      oscillation (HFO) to rescue this infant had no effect, intratracheal instillation
      of epinephrine (EP) showed dramatic improvement of her respiratory status. This
      clinical course showed that the patient did not have pulmonary hypoplasia but
      might have severe airway obstruction and this airway obstruction may be the major
      cause of 'dry lung syndrome'. We postulate that when a newborn with suspected
      pulmonary hypoplasia is unresponsive to respiratory support. HFO should be
      administered. If HFO is ineffective in relieving the respiratory distress, one
      should suspect the presence of airway collapse and administer a bronchodilator
      such as EP. If the infant improves, a diagnosis of 'dry lung syndrome' may be
      assumed.

PMID- 7825454
TI  - Preschool sarcoidosis manifesting as juvenile rheumatoid arthritis: a case report
      and a review of the literature of Japanese cases.
AB  - Nine Japanese cases of sarcoidosis in children of 4 years of age or younger have
      been reported in the literature, including the case presented here. Clinically,
      preschool sarcoidosis is distinctly different from that of older children; it is
      characterized by a triad of skin, joint and eye lesions without pulmonary
      involvement. It is easily confused with juvenile rheumatoid arthritis which also
      presents the symptoms of arthritis and uveitis. We report on a patient with
      preschool sarcoidosis who was initially diagnosed as having juvenile rheumatoid
      arthritis. We recommend prompt skin biopsy to differentiate between these
      conditions.

PMID- 7825455
TI  - Interchange trisomy 9 due to maternal t(6;9) translocation.
AB  - The occurrence of interchange trisomy due to a 3:1 malsegregation has been
      documented in only a few cases with trisomy 21. We describe the first case of
      interchange trisomy 9 due to a maternal t(6:9) translocation. The patient, a boy
      neonate who died immediately after birth, had intra-uterine growth retardation,
      specific craniofacial features including microcephaly with a high forehead, low
      set ears, upslanting short palpebral fissures, microphthalmia, bulbous nose and
      micrognathia, cryptorchidism, cystic kidney and various skeletal anomalies. His
      phenotype was consistent with that of the trisomy 9 syndrome. Cytogenetic
      analysis showed his karyotype of 47,XY,-6, + der(6), +
      der(9)t(6;9)(q27;q21.1)mat. The present report indicates that a very rare
      interchange mode of a 3:1 segregation can give rise to a live birth with full
      trisomy 9 in female carriers with reciprocal translocations involving the
      proximal long arm of chromosome 9.

PMID- 7825457
TI  - High intensity in the globus pallidus on proton and T2-weighted MRI in a case of
      dentato-ruburo-pallido-luysian atrophy of myoclonus epilepsy type.
AB  - Although marked atrophy of the tegmentum of the mid-brain is a known computed
      tomography (CT) and magnetic resonance imaging (MRI) feature in patients with
      dentato-ruburo-pallido-luysian atrophy (DRPLA), this is the first report of
      marked high signal intensity of the globus pallidus on proton and T2-weighted MR
      images in a patient in the early stage of DRPLA of the myoclonus epilepsy type.
      We suggest that the globus pallidus may be involved in the early stage of DRPLA
      of this type. Magnetic resonance imaging is considered to be useful for the early
      detection of involvement of the globus pallidus and in the clinical diagnosis of
      DRPLA.

PMID- 7825456
TI  - Spinal muscular atrophy in trizygotic triplets.
AB  - The clinical, electrophysiological, pathological and genetic findings in
      trizygotic triplets with spinal muscular atrophy (SMA) are reported. The first
      child was clinically affected shortly after birth and the third one first showed
      symptoms at 1 month of age. Electromyography and a muscle biopsy provided
      evidence of lower motor neuron disease. The second child remains clinically
      normal, but electromyography showed fibrillation potentials and regular
      spontaneous motor unit activity at rest. Genetic linkage analysis revealed that
      the two siblings with typical type 1 SMA had the same chromosome 5q haplotype,
      and that the second child had a different haplotype. It is considered that in
      this family there is a link to SMA 5q and there is little possibility that the
      second child is affected. These data emphasize the need to adhere to strict
      clinical criteria for the diagnosis of chromosome 5q SMA.

PMID- 7825458
TI  - Proceedings of the International Symposium on Breast Feeding and Gut Immunology.
      Tokyo, Japan, September 5-8, 1994.

PMID- 7825459
TI  - Development of mucosal immune function in man: potential for GI disease states.
AB  - The human mucosal immune system is structurally mature and has all the necessary
      cellular components to generate an immune response at birth. However, in the
      absence of dietary antigens and bacterial flora, there are no secondary follicles
      in the Peyer's patches and virtually no immunoglobulin A plasma cells in the
      lamina propria. Reactive follicle centers develop after birth but it takes 2
      years for mucosal IgA plasma cell density to reach adult levels. T cells are
      present in the epithelium and lamina propria at birth, albeit at a lower
      frequency than later in life and there are major differences in phenotype between
      T cells in fetal intestine and postnatal intestine. There is no information on
      the impact of the massive antigenic challenge at birth on the mucosal immune
      system. Well-documented deficiencies in the ability of the blood T cells of the
      neonate to produce interleukin-4 and interferon-gamma may also occur in the
      intestine. It is still an open question whether it is better to try to prevent
      immunological sensitization of the newborn by avoiding potential allergens (i.e.
      cow's milk), or whether early exposure (as happens when premature infants are
      given formula feeds) might tolerize the infant. Hydrolysed cow's milk formulae
      are probably less antigenic than whole cow's milk and have been widely used in
      the treatment of cow's milk allergy. Some thought is now being given as to
      whether the prophylactic use of hydrolysates can reduce cow's milk allergy in 'at
      risk' infants.

PMID- 7825460
TI  - Mucosal immunity and strategies for novel microbial vaccines.
AB  - Infectious diseases continue to be the leading cause of morbidity and mortality
      worldwide. Increased awareness of the fact that mucosal membranes are the most
      frequent portals of entry of pathogenic microorganisms has prompted studies aimed
      at the development of vaccination protocols and antigen delivery systems that
      would lead to an increased protection of mucosae. Although systemic and strictly
      local immunizations are of limited effectiveness in the induction of mucosal
      protection, ingestion or inhalation of antigens results in a generalized immune
      response manifested by the appearance of specific antibodies of the secretory
      immunoglobulin (Ig) isotype in external secretions due to the dissemination of
      IgA precursor cells from IgA-inductive lymphoid tissues. Furthermore, additional
      inductive sites strategically positioned at the opening of the respiratory and
      digestive tracts may also be suitable targets for induction of immune responses
      at desired effector sites. To prevent degradation and the increase of ingested
      antigens absorption, novel strategies including enclosure of antigens into
      biodegradable microspheres, liposomes or their expression in viral and bacterial
      vectors and plants are currently being considered. Forthcoming technological
      advances in antigen preparation and routes of delivery will undoubtedly have a
      profound impact on immunization practices in the future.

PMID- 7825461
TI  - Food sensitive enteropathy: overview and update.
AB  - There are two types of food sensitive enteropathy; permanent and temporary.
      Celiac disease belongs to the former, the temporary food sensitive enteropathies
      of early childhood to the latter. A food sensitive enteropathy is characterized
      by an abnormal small intestinal mucosa while having the offending food in the
      diet; the abnormality is reversed by an elimination diet, only to recur once more
      on challenge with the relevant food. These disorders are temporary and may follow
      gastroenteritis. Cow's milk sensitive enteropathy is the most frequent and best
      known example but soy protein, egg, fish, chicken meat, ground rice and probably
      gluten may also temporarily damage the small intestinal mucosa in infancy.
      Treatment is with an elimination diet and protein hydrolysates as a cow's milk
      substitute. The reason why these enteropathies are temporary has not yet been
      established.

PMID- 7825462
TI  - The regulation of intestinal hypersensitivity reactions to ovalbumin by omega-3
      fatty acid enriched diet: studies of IEL and LPL in mucosal damage.
AB  - In order to clarify the mechanisms of food-sensitive enteropathy, a food
      hypersensitive model was generated by feeding ovalbumin to female BALB/c mice
      after intraperitoneal injection of cyclophosphamide and morphological and
      immunological changes in the gut mucosa were investigated. Villus atrophy, crypt
      hyperplasia and increased numbers of intra-epithelial lymphocytes (IEL) were
      confirmed in this model, as seen in food-sensitive enteropathy in humans.
      Subpopulations of IEL and lamina propria lymphocytes were enumerated by
      immunohistochemical observation. CD8-positive cells were increased both in
      epithelium and lamina propria, whereas CD4-positive cells were decreased in
      lamina propria. We document here that orally administered food antigen actually
      induces food-sensitive enteropathy and mucosal damage is generated by lymphocytes
      that infiltrate the intestinal mucosa. We also investigated the effect of feeding
      an omega-3 fatty acid-enriched diet in this model and found that it was efficient
      in attenuating mucosal damage.

PMID- 7825463
TI  - Breast feeding: overview and breast milk immunology.
AB  - The transfer of host defence capacity to the human offspring provides a
      remarkable model of passive transfer of immunity. In fact it may also provide an
      example of active immunization. The transfer of mucosal protection via breast
      feeding offers many additional advantages for the mother and infant. Through its
      contraceptive effects it increases the spacing between births, thus diminshing
      the infant mortality and the burden on the mother. It also enhances bonding
      between mother and child, it seems to increase the IQ and school result of the
      infant and might decrease the risk of certain malignancies and perhaps of
      juvenile diabetes. A fully breast-fed infant receives as much as 0.5-1 g of
      secretory immunoglobulin A (SIgA) antibodies daily, the predominant antibody of
      human milk. This can be compared to the production of some 2.5 g of SIgA per day
      for a 60 kg adult. These SIgA antibodies have been shown to protect against
      Vibrio cholerae, ETEC, Campylobacter, Shigella and Giardia. Furthermore, milk is
      rich in receptor analogues for certain epithelial structures which microbes need
      for attachment to host tissues as an initial step in infections. Thus the
      adherence of Haemophilus influenzae and pneumococci for example to
      retropharyngeal cells is efficiently inhibited by human milk. This may be one
      explanation for the fact that breast-fed babies have less otitis media than the
      non-breast-fed. Other milk factors like lysozyme and lactoferin may contribute to
      the host defence, but this has not yet been well defined. However, human milk
      also supports the well-being of the infant by being anti-inflammatory.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7825464
TI  - Early infant feeding and micro-ecology of the gut.
AB  - Newborn infants are rapidly colonized by both aerobic and and anaerobic bacteria,
      initially with about 50% of each type. Several factors related both to the infant
      and its environment influence the composition of the intestinal microflora
      quantitatively as well as qualitatively. Major ecological disturbances are
      observed in newborn infants treated with antimicrobial agents. One way of
      minimizing the ecological disturbances, which may be seen in infants treated in
      neonatal intensive care units, is to provide them with fresh breast milk from
      their mothers and to use antimicrobial therapy only under strict clinical
      indications.

PMID- 7825465
TI  - New approaches to the study of human pediatric disease.
AB  - The intestinal epithelium may modulate childhood gastrointestinal disease
      activity, particularly in chronic inflammatory bowel disease. The epithelium is
      in direct contact with the intestinal lumen and is ideally placed to act as a
      communication between the intestinal environment and the immune cells of the
      mucosa. Interaction is possible through the production of cytokines by
      enterocytes and the expression of surface molecules on the basolateral membrane.
      The study of how luminal contents can modulate enterocyte gene expression is
      central to this process, but the molecular mechanisms by which such interactions
      occur are not well understood. This review discusses possible molecular pathways
      between the intestinal lumen and the enterocyte and how they can be examined
      experimentally. Finally, the importance of enterocyte gene expression in human
      health and disease is reviewed.

PMID- 7825466
TI  - Sorrento studies of diet and fecal flora in the newborn.
AB  - The fecal flora of a breast-fed baby is very different from that of a bottle-fed
      baby. This paper reviews five previous studies, performed at this hospital
      concerning the effect of various dietary components (whey proteins, casein,
      lactoferrin, iron, nucleotides) on the fecal flora. The babies received either
      breast milk or one of the test formulas from birth. Fecal samples were examined
      by quantitative microbiological methods at 4 and 14 days and at various intervals
      thereafter. By 14 days differences in the fecal flora were established. Among
      breast-fed babies bifidobacteria, lactobacilli and staphylococci were predominant
      organisms, whereas in the formula-fed babies the predominant organisms were
      enterococci, coliforms, and Bacteroides. A whey-based formula without bovine
      lactoferrin, iron or nucleotides gave a flora a little closer to but still remote
      from the breast-fed one. Despite extensive modification of cow's milk in the
      manufacture of a modern infant formula, the fecal flora of bottle-fed babies
      remains substantially different from that of breast-fed babies.

PMID- 7825467
TI  - A review: the active peptide of lactoferrin.
AB  - A potent antimicrobial peptide, 'lactoferricin', was found to be generated upon
      gastric pepsin cleavage of lactoferrin. The active peptide consists mainly of a
      loop of 18 amino acid residues, derived from the N-terminal region of the
      lactoferrin molecule. Like various other antimicrobial peptides that display
      membrane-disruptive properties, it contains a high proportion of basic amino acid
      residues. A physiologically diverse range of micro-organisms was tested and found
      to be susceptible to inhibition by this natural peptide including Gram-negative
      and Gram-positive bacteria, yeasts and filamentous fungi. Its antimicrobial
      effect against sensitive micro-organisms was lethal. Electron microscopy studies
      revealed that it induces a profound change in cell ultrastructural features and
      causes substantial cell damage in bacteria and fungi. These findings suggest the
      possibility that active peptides of lactoferrin may have a role in the host
      defense against microbial disease. If produced in substantial quantities in vivo
      such peptides could have important physiological significance, especially in
      nursing infants.

PMID- 7825468
TI  - Milk proteins, cytokines and intestinal epithelial functions in children.
AB  - This paper discusses the relationship between food antigens, lymphocytes and the
      epithelial properties of the jejunum in children with cow's milk allergy.
      Experimental results indicate that increased protein permeability is not the
      primary cause of cow's milk allergy. Rather, results are interpreted as a
      secondary effect of an abnormal immunological response leading to mucosal
      inflammation and impairment of the endocytic process by the intestinal epithelial
      cells. Stimulation by cow's milk proteins caused the lymphocytes from infants
      with cow's milk allergy to release more tumor necrosis factor-alpha TNF alpha
      than those from control infants. After appropriate antigenic stimulation, the
      cytokines released by the activated lymphocytes from these infants perturbed
      epithelial function, in particular its barrier capacity. Tumor necrosis factor
      alpha, together with gamma interferon are involved in these adverse effects. It
      is thought that bovine beta-lactoglobulin present in the intestinal lumen may be
      responsible for the secretory diarrhea observed in children with cow's milk
      allergy, as a consequence of stimulation of electrogenic chloride secretion. In
      addition, luminal foreign protein may stimulate the submucosal cells. As a
      consequence, the submucosal release of mediators, including lymphokines, might
      alter the intestinal epithelial barrier. In conclusion, in physiological
      conditions, the subepithelial tissue that comprises the immune system and many
      other systemic systems receive information on the antigenic content within the
      intestinal lumen via the intestinal epithelium.

PMID- 7825469
TI  - Uptake of antigens: role in gastrointestinal disease.
AB  - The intestine is exposed to a wide variety of macromolecules. Because
      macromolecules are antigenic, mechanisms have evolved in the gastrointestinal
      tract to regulate their absorption. Macromolecular uptake can be beneficial in
      delivering essential factors for growth and in sampling the antigenic milieu of
      the gastrointestinal tract. Specific transport mechanisms exist to execute this
      physiological absorption. However, inappropriate and uncontrolled antigen
      transport may occur in disease states, or as a prelude to disease states in the
      gastrointestinal tract. Such transport may result in immune responses that are
      harmful. In this review we examine both physiological transport of macromolecules
      through epithelia and through M cells. We also discuss uncontrolled transport and
      its relation to disease states. We conclude by examining the interrelationship
      between antigen transport and an altered immune system in the establishment of
      gastrointestinal disease.

PMID- 7825470
TI  - [Micro- and macroreplantation of the upper and lower extremity].

PMID- 7825471
TI  - [Calcified inclusions in a popliteal cyst as a rare cause of persistent knee pain
      and recurrent effusions].
AB  - Popliteal cysts may occur with diseases of the knee and may cause several
      complications. We report about a patient with a popliteal cyst, that contained
      calcified concrements after a femur fracture and a complex knee injury and that
      we found to be a rare cause of persisting knee pain and effusions. The etiology
      of the concrements will be discussed, that we think are more likely to be
      posttraumatic loose joint bodies than traumatically induced chondromatosis.

PMID- 7825472
TI  - [Variability of the length and joint angle proportions of the distal radius].
AB  - The anatomical proportions of length and degree of joint-angles on the distal end
      of the radius and ulna show an wide variety in our population. 926 x-rays of
      "normal" and injured wrist-joints performed during 1984-89 were exactly measured
      and compared in respect to length and joint-angles of radius and ulna. Comparing
      the results with earlier reports in the literature it can be demonstrated that
      apparently there has been a remarkable change of the anatomical proportions in
      this region in the course of time and generations. The knowledge of the
      anatomical conditions is essential in acute traumatology as well as in
      corrections of posttraumatic wrist-deformities by osteotomy, bone grafting and
      internal fixation in regard to a posttraumatic restricted joint-function.

PMID- 7825473
TI  - [Indications for surgical treatment of clavicular fractures].
AB  - Most fractures of the clavicle can be successfully treated by conservative
      management. In few cases however primary or secondary operative stabilisation is
      necessary. Good results can only be obtained considering clearly defined
      indications and correct surgical techniques. Reconstruction-plates and Small
      dynamic-compression-plates have proved best to provide internal fixation. In a
      period of 6 years 262 patients with fractures of the clavicula were treated in
      the Unfallchirurgischen Klinik Hofheim, eleven of which by operative means. We
      report on those 11 patients that have undergone surgical treatment. Indications,
      operation techniques and results will be presented and discussed in comparison to
      recent literature.

PMID- 7825474
TI  - [Delayed management of rupture of the Achilles tendon. Long-term follow-up in
      comparison with early operation].
AB  - At the Orthopedic Clinic of the University Homburg/Saar 32 delayed (8 days to 7
      months) treated ruptures and 32 immediately (< 48 hours) treated ruptures of the
      Achilles tendon were followed up by clinical tests and sonographic examination
      and were compared with regard to the final results and the complications. There
      was no significant difference in the functional results. The rate of
      complications, which made a second operation necessary, was significantly higher
      in the group of delayed repair of the Achilles tendon rupture.

PMID- 7825475
TI  - [Arthrofibrosis after replacement-plasty of the anterior cruciate ligament-
      incidence, causes, therapy].
AB  - The objective of the study was to assess prospectively the percentage of patients
      with restricted range of motion (arthrofibrosis) after ACL-plasty and to assess
      the clinical benefit of arthroscopic surgery. We had arthrofibrosis in 9 out of
      74 cases (12%). In 8 cases there was a combined lag of flexion and extension and
      in one case there was only a lag of extension. In all patients range of motion
      could be improved by arthroscopic surgery. There was a significant raise in
      extension (13.3 degrees) and in flexion (28.7 degrees). In the arthrofibrosis
      group more patients had undergone surgery for acute ACL-rupture (66%) than in the
      group without arthrofibrosis (32%).

PMID- 7825476
TI  - [Laryngeal insufficiency as a post-traumatic complication of facial skull
      injury].
AB  - Laryngeal incompetence is characterised by incoordination in deglutition and
      fluid leakage around the tracheostomy tube. It occurs very rarely and is
      attributed to injury of the recurrent laryngeal nerve. To our experience this
      condition demands no treatment and gradually disappears. In this paper we present
      a case of a 24-year-old male patient with facial fractures presenting laryngeal
      incompetence.

PMID- 7825477
TI  - [Injury of the popliteal artery as a complication of knee dislocation].
AB  - Dislocation of the knee is rarely seen. Only 15 patients with a knee dislocation
      were treated in the surgical department of the university hospital in the last 18
      years. One patient had bilateral dislocation of the knee. Injury to the popliteal
      artery is severe and often endangers the extremity. In seven patients with knee
      dislocation arterial ischemic was detected. Five patients were treated for
      arterial damage (31.25%).

PMID- 7825478
TI  - Tacrine for Alzheimer's disease: why is it not available on prescription to UK
      sufferers?

PMID- 7825479
TI  - Chronic haemodialysis for very old patients.
AB  - There is in the Western World a progressive ageing of the population, and
      consequently haemodialysis patients are also getting older. Some ethical
      questions have been raised as a consequence of the economic issues related to the
      scarcity of available resources. In this paper we review our experience in the
      treatment of very old chronic haemodialysis patients. Fifty patients (7.2% of our
      haemodialysis patients) aged over 80 years at the beginning of dialysis were
      included (f = 25, m = 26, age = 82.6 +/- 0.3 years). In 42% of the patients the
      aetiology of renal disease was unknown. In the remainder, the aetiology was:
      interstitial nephritis 26%, hypertensive nephrosclerosis 14%, chronic
      glomerulonephritis 8%, diabetes 8% and polycystic disease 2%. There was a great
      comorbidity: intradialytic hypotension 82%, cardiac disease 74%, gastrointestinal
      disease 32%, cerebrovascular disease 26%. Vascular access related problems were
      the main reason for hospitalization. The major cause of death was vascular
      (cardiac and cerebral disease). Actuarial survival was 89%, 78%, 56% and 48% at
      6, 12, 24 and 36 months, respectively. We think that haemodialysis is the best
      available choice for treating very old chronic renal failure patients. However
      further studies are needed to improve the quality of life of these patients.

PMID- 7825480
TI  - Finding colorectal tumours with an immunological faecal occult blood test in
      symptomatic primary health care patients.
AB  - The aim of this prospective study was to investigate whether an immunological
      double faecal occult blood test (Fecatwin-S/FECA-EIA) can be used in screening
      patients with symptoms suggestive of colonic or rectal origin in primary health
      care. Altogether 523 patients were referred to the study by general
      practitioners. Three kits were used for the faecal samples and each time the
      sample was taken from two places of the faeces. If the guaiac test (Fecatwin-S)
      was positive, the immunological test (FECA-EIA) was performed. All 71 patients
      with an immunotest absorbance value of over 0.8 were investigated with
      colonoscopy and this group had 13 cancers, eight adenomas and one hyperplastic
      polyp. A control group of 41 consecutive patients with an absorbance value under
      0.8 had one adenoma and three hyperplastic polyps. The uninvestigated FECA-EIA
      negative patients had no malignant colorectal tumours in the mean follow-up
      period of 2.2 years according to hospital records. All cancers had very high
      absorbance values, the mean value being 2.461. With adenomas the mean absorbance
      value was 1.912 and with hyperplastic polyps 0.814. Most of the diagnosed cancers
      and adenomas were in patients over 65 years of age. The study indicates that the
      immunological occult blood test is a useful tool for a general practitioner in
      finding bleeding colorectal tumours. The number of needless clinical examinations
      can be lowered which is important especially among elderly patients. However, the
      test-negative patients should be retested or investigated if symptoms continue.

PMID- 7825481
TI  - Strength, power and related functional ability of healthy people aged 65-89
      years.
AB  - This cross-sectional study was designed to examine the effects of healthy ageing
      on muscle strength, power, and potentially related functional ability. Subjects
      were recruited through local and national newspapers and inclusion was based on
      strict health criteria, by questionnaire. Isometric knee extensor, isometric
      elbow flexor and handgrip strength, leg extensor power, timed rise from a low
      chair, lifting a weighted bag on to a surface, and stepping unaided on to boxes
      of different heights were measured in 50 men and 50 women, evenly distributed
      over the age range 65-89 years. The differences in isometric strength and leg
      extensor power over the age range were equivalent to 'losses' of 1-2% per annum
      and approximately 3 1/2% per annum, respectively. The decline of explosive power
      was faster than the decline of knee extensor strength in men (p = 0.0001), but
      not significantly so in women (p = 0.08). Power standardized for body weight
      influenced chair rise time and step height. Isometric knee extensor strength
      standardized for body weight influenced chair rise time.

PMID- 7825482
TI  - Development and reliability of the Royal College of Physicians stroke audit form.
      UK Stroke Audit Group.
AB  - This article reports the development of an audit form for assessing the quality
      of stroke care from medical records. A consensus conference to define standards
      was followed by testing of pilot versions of the audit form. Then formal
      assessment of inter-rater reliability was carried out in four centres using 76
      medical records, each assessed by two of eight auditors. Inter-rater reliability
      was acceptable, especially when medically qualified auditors were used.

PMID- 7825483
TI  - Eligibility of acute stroke patients for pharmacological therapy.
AB  - The aims of this study were to analyse the characteristics of patients with acute
      stroke and to ascertain the number of patients meeting eligibility criteria
      commonly applied in clinical trials of pharmacological agents for ischaemic
      stroke. Details of all consecutive admissions with a diagnosis of acute stroke (n
      = 410, 55% female, mean age 77, range 22-99 years) admitted over a 12-month
      period to a district general hospital were recorded. Major exclusion criteria
      used in acute stroke trials were applied to data collected from the study
      patients. Exclusion criteria were met by 386 (94%) stroke patients, 188 (46%) had
      admission delay > 12 hours, 85 (21%) had pre-existing major disability, 80 (20%)
      minor stroke, 66 (15%) had coexisting severe illness, 51 (12%) were unconscious,
      and 30 (7%) had major electrolyte or ECG abnormalities. One hundred and five
      (26%) had two or more exclusion criteria. The majority of acute stroke patients
      admitted to a district general hospital would be likely to be excluded from most
      current pharmacological treatment studies.

PMID- 7825484
TI  - A community-based population study of vertebral fractures in 85-year-old men and
      women.
AB  - Radiographic examinations for the presence of vertebral fracture between T4 and
      L5 were performed in a random sample of 85-year-old women (n = 304) and men (n =
      158) who participated in a longitudinal study in Gothenburg. A vertebral fracture
      was defined as an anterior/posterior (A/P) vertebral height ratio of 0.66 or
      less. A severe vertebral fracture was defined as a compression of vertebral
      height of more than 33% both at the anterior and posterior edges compared to the
      posterior edge of the adjacent vertebral body. Bone mineral density was measured
      with dual photon absorptiometry in the right calcaneus. The most common site for
      vertebral fractures was L1 in women and Th12 in men. Bone mineral density in men
      at the age of 75 showed a significant correlation with vertebral fractures at 85
      years of age (p < 0.001). This was not the case for women. Stepwise logistic
      analysis revealed that women with vertebral fractures at 85 years of age had more
      significant back pain, shorter stature, and more often a history of another
      fracture and/or chronic treatment with corticosteroids. In men, muscle strength,
      marital status and body weight at age 85 were the only factors significantly
      associated with vertebral fractures.

PMID- 7825485
TI  - Acute pneumothorax: a comparison of elderly with younger patients.
AB  - This report compares the presentations and outcome of pneumothorax in 11 patients
      aged over 65 with 15 patients aged 20-35 years. Information was retrospectively
      collected from the charts regarding modes of presentation and the course of the
      illness. A questionnaire was sent to the general practitioners of the older group
      asking about the long-term outcome relating to functional status. Older patients
      were more likely than younger to present primarily with dyspnoea. The classical
      symptom of acute onset of pleuritic chest pain was present in ten of the 15
      younger patients but in only two of the older patients. There were also
      statistically significant associations of the elderly patients with the
      following: radiological evidence of pre-existing lung disease; absence of
      pleuritic chest pain on admission; atypical or absent pain; a major delay from
      symptom onset to presentation; the diagnosis being clinically missed prior to
      chest radiography; and prolonged hospitalization. Nine of the 11 elderly patients
      were eventually independent at home.

PMID- 7825486
TI  - Hyperinsulinaemia and Alzheimer's disease.
AB  - Because the aetiology of Alzheimer's disease (AD) remains unclear, and fasting
      hyperinsulinaemia has been incriminated in several human diseases, we examined
      the relationship between AD, fasting plasma insulin, glucose, body mass index and
      waist: hip ratio in 24 men and 24 women aged 58-90 years of whom half had
      probable AD. AD patients were randomly selected from the Bristol Memory Disorders
      Clinic, while controls were chosen from patients' spouses and the local
      community. Women with AD, compared with controls, have higher plasma insulin (p =
      0.04), higher glucose (p = 0.04), and higher body mass index (p = 0.01). Similar
      differences were present in men but were not statistically significant except for
      body mass index (p = 0.03). We conclude that patients with AD have
      hyperinsulinaemia and insulin resistance, and this may be secondary to being
      overweight but a causal relationship cannot be excluded.

PMID- 7825487
TI  - Cardiovascular autonomic functions in Alzheimer's disease.
AB  - We investigated cardiovascular autonomic functions in 23 patients with
      Alzheimer's disease (AD) and 23 age-matched control subjects. The vagal
      parasympathetic function was assessed with R-R interval variation (RRIV), and
      sympathetic function with sympathetic skin response (SSR) and orthostatic
      cardiovascular reflexes. Compared with controls, the AD patients had
      significantly depressed RRIV during rest (6.4 +/- 1.3% vs. 7.5 +/- 1.6%, p <
      0.02) and deep breathing (12.6 +/- 4.6% vs. 17.0 +/- 5.1%, p < 0.006), but all AD
      patients had normal SSR. After standing for 3 minutes from supine, the changes of
      blood pressure and heart rate from baseline in AD patients did not differ from
      those in controls. The AD patients had a lower systolic blood pressure than
      controls in both supine (130.7 +/- 17.4 vs. 145.4 +/- 20.7 mmHg, p < 0.02) and
      standing (129.2 +/- 20.1 vs. 146.6 +/- 21.1 mmHg, p < 0.008) positions,
      especially in those patients with more severe dementia. We conclude that AD
      patients have mildly impaired autonomic functions, mainly in vagal
      parasympathetic functions. The pathogenesis and clinical significance of low
      blood pressure in AD needs further study.

PMID- 7825488
TI  - The effects of pressure and shear on skin microcirculation in elderly stroke
      patients lying in supine or semi-recumbent positions.
AB  - The effects of external pressure and shear on the skin microcirculation over the
      sacral area, which is known as a high risk area for pressure sore formation, were
      studied in 30 elderly patients. The skin blood cell flux (SBF) was measured using
      the laser Doppler technique, with the patient first at rest in lateral position,
      then lying for 30 minutes in supine or semi-recumbent 45 degrees position, and
      finally in lateral position. Elderly high-risk patients (G2), most of them more
      than two years post-stroke, had a lower body mass index and a reduced sacral skin
      fold compared with non-risk patients (G1). The SBF in G2 decreased 28% in supine
      and 14% in 45 degrees position, whereas the SBF in G1 increased 35% in supine and
      13% in 45 degrees position. Spontaneous movements up to seven times per 30
      minutes were registered, even during sleep, and were evident by direct
      observation of the recorded charts as a temporary SBF increase. The risk for skin
      ischaemic damage over the sacral area of elderly risk patients was evident in
      both positions, especially with the patients lying in supine position. When
      increasing the upper body slope in G2 from horizontal to 45 degrees, an inability
      to recover a satisfactory blood supply after the ischaemic insult was found.
      Discomfort from compressive and shear forces initiates changes in posture, even
      in elderly patients prone to tissue breakdown. Occasional relief of pressure was
      in most patients followed by temporary increase in skin blood flow with
      concomitant temperature increase. This most probably protected them from
      developing skin lesions.

PMID- 7825489
TI  - Sleep and ageing: the effect of institutionalization on subjective and objective
      characteristics of sleep.
AB  - To assess the impact of institutionalization on sleep/wake characteristics of
      elderly people, we compared subjective (study I: n = 160) and objective (study
      II: n = 30) sleep/wake measures of non-demented institutionalized subjects and
      age-matched non-institutionalized controls. We also evaluated the prevalence and
      causes of various sleep disturbances. The three living conditions, i.e.
      independently living (IL), service home (SH) and nursing home (NH) were
      respectively assumed to have minimal, moderate and maximal effects upon the
      timing, the amount and the quality of the sleep/wake behaviour of the persons
      involved. Study I showed that a higher level of institutionalization was
      significantly (p < 0.05) associated with phase-advanced sleep/wake patterns,
      increased amounts of time spent in bed during the 24-hour period and increased
      usage of prescribed sedative-hypnotic drugs. Poor sleep quality and disturbed
      sleep onset occurred significantly mostly in the SH group. No differences between
      groups were demonstrated with respect to the prevalence of disturbed sleep
      maintenance, parasomnias and difficulty with awakening and their possible causes,
      except for environmental noise which was exclusively reported by
      institutionalized subjects. No differences between groups for any of the
      objective measures were found (study II). Overall, our findings are in line with
      previous findings on this topic, although the observed high rate of poor sleep
      quality and sleep disturbances and their associated causes as observed in
      institutionalized subjects also occurs in an age-matched non-institutionalized
      population.

PMID- 7825490
TI  - A general population survey of rest cramps.
AB  - Two hundred and eighteen subjects, out of 250 individuals taken from a general
      practice register, returned completed questionnaires giving details about rest
      cramps, and a further 15 were contacted by telephone. The overall prevalence of
      rest cramps in the survey population was 37%. The symptom was more prevalent in
      older subjects. Rest cramps were most commonly experienced in the muscles of the
      leg, in 83% of the 86 cramp sufferers. Symptoms were usually present at night
      (73%). On average cramp episodes lasted for 9 min (95%CI 6.7-11.2). Most cramps
      sufferers experienced symptoms infrequently, but 40% had cramp episodes more than
      three times per week and 6% complained of at least one episode per day or night.
      Twenty-one per cent of cramp sufferers described their symptoms as very
      distressing. A minority, 32% of the 86 cramp sufferers, had reported the symptoms
      to a general practitioner although the 86 subjects self-rated their health more
      negatively than the individuals without muscle cramps. There was a significant,
      positive association between rest cramps and symptoms of angina or intermittent
      claudication although these two factors only accounted for 12% of the variance,
      suggesting that peripheral vascular disease may play a relevant but limited role
      in the aetiology of rest cramps.

PMID- 7825491
TI  - Age, smoking and the activity of the mono-oxygenase aryl hydrocarbon hydroxylase
      in isolated human peripheral blood monocytes.
AB  - Age-associated changes in the microsomal mono-oxygenase enzyme, aryl hydrocarbon
      hydroxylase (AHH), were investigated in peripheral blood monocytes isolated from
      young and elderly subjects. Young subjects were selected from the age group < 35
      years; elderly subjects were > 70 years. AHH activity, expressed as nM 3-hydroxy
      benzopyrene formed/10(6) cells/h of incubation, was similar in young and elderly
      non-smokers (elderly = 6.7 +/- 1.8; young = 9.1 +/- 0.9; p > 0.05). In smokers,
      contrary to some previous reports, AHH activity was not significantly higher than
      in non-smokers of similar age (elderly smokers = 8.6 +/- 1.0; young smokers =
      10.5 +/- 2.4; p > 0.05). There was no significant difference between young and
      elderly smokers (p > 0.05). We conclude that: (a) AHH activity is similar in
      young and old non-smoking individuals; (b) no significant differences were
      detected in in vivo induction of this enzyme activity between smokers and non
      smokers.

PMID- 7825492
TI  - The hearing-aid battery: a hazard to elderly patients.
AB  - Owing to the severity of its corrosive effects, an alkaline hearing-aid battery
      in the external auditory meatus is an otological emergency. This report
      emphasizes the particular risk to confused elderly patients and points out that a
      delay in diagnosis is common. Aetiology, clinical features and treatment are
      discussed with reference to three recent cases.

PMID- 7825493
TI  - Prevalence of urinary tract infection post-urodynamics in older people.

PMID- 7825494
TI  - [Acquired immunodeficiency syndrome and ophthalmology].

PMID- 7825495
TI  - [Quantitative analysis of glycosaminoglycans in tear fluids during corneal
      epithelial wound healing in rabbits].
AB  - We performed quantitative analyses of glycosaminoglycans in the tear fluids in a
      rabbit wound healing model. We ablated rabbit corneal epithelium with trephine
      and spatula, and sampled tear fluids before the epithelial ablation, and at 3,
      24, 48, and 72 hours after it. After an instillation of 200 microliters saline
      solution in the conjunctival sac, as much tear fluid as possible was collected
      from the lower cul-del-sac. The glycosaminoglycans in the tears were then treated
      with chondoroitinase ABC to make fractions of disaccharides. The quantities of
      disaccharides were determined with high-performance liquid chromatography as
      weight per unit protein in the tears. The concentrations of delta Di-HA in the
      tear fluids at 3 and 24 hours were significantly higher than those before the
      treatment and returned to the initial value at 72 hours after making the
      epithelial wound. Among the disaccharides of chondroitin sulfate, delta Di-0S and
      delta Di-6S showed a significant increase at 3 hours after the treatment but
      delta Di-4S did not show any significant variation. The results suggest that the
      glycosaminoglycans in the rabbit tear fluids may play an important role in the
      corneal epithelial wound healing process.

PMID- 7825496
TI  - [Distribution of the 70kD stress protein in corneas with alkali burns].
AB  - The immunolocalization of 70kD stress-protein (SP 70) was investigated in white
      rabbit corneas with alkali burns. Corneal alkali burn injuries were induced with
      6 mm circular filter paper discs soaked in 1N NaOH. Corneas of 1, 3, 5, and 7
      days after alkali injury were immunostained with mouse monoclonal anti-SP 70
      antibody. In the control rabbit cornea, immunostaining for SP 70 was observed in
      the nuclei of the basal cells and of the wing cells. On day 1 after alkali
      injury, total epithelial defect was observed. Immunostaining for SP 70 was not
      seen in corneas with total epithelial defect. Three days after injury, epithelial
      resurfacing with corneal edema was observed. Basal cells showed immunostaining
      for SP 70 in their nuclei and cytoplasm. Five days after injury, irregular basal
      cells and a few wing cells with cytoplasmic processes were recognized. Both cells
      showed diffuse cytoplasmic and nuclear immunostaining for SP 70. Seven days after
      injury, the corneal wound was healed, and SP 70 was observed in the nuclei of the
      epithelial cells again. It appears that SP 70 has a role in corneal epithelial
      healing after alkali burn injury.

PMID- 7825498
TI  - [Light-dependent changes of ribosome distribution in photoreceptor inner segments
      of the mouse retina].
AB  - We studied the distribution pattern of free ribosomes in the photoreceptor inner
      segments of adult mice with reference to environmental light. Eyeballs were
      obtained from animals at the light or dark phase of the ordinary cyclic light,
      and photoreceptor inner segments were examined by electron microscopy. In the
      light phase, free ribosomes were distributed in a random fashion, although
      meticulous observations revealed that they appeared to be arranged either in a
      spiral or linear form, or in isolation. In the dark phase, several free ribosomes
      were arranged in a clustered fashion. When animals were kept in continuous
      darkness as long as 27 hours, most of the inner segment free ribosomes showed a
      clustered pattern similar to that in the dark phase of the cyclic light. We
      discussed the light-dependent configurational changes of ribosomes with respect
      to their activity or inactivity in protein synthesis.

PMID- 7825497
TI  - [Effects of Chinese medicine on bovine ciliary muscles].
AB  - We studied the effects and characteristics of Chinese medicines (Gorei-san (I),
      Saiko-keishi-to (II), Ryokei-jutsu-kan-to (III), Shokenchu-to (IV)), on the
      contractions (A) of bovine ciliary muscles. Ciliary muscle strips (width 4 mm x
      length 6 mm) were prepared and were contracted by a cholinergic agent, carbachol
      (10(-5)M). The 4 Chinese medicines were diluted to the concentrations of 10(-3)
      10(-6) of each adult dosage per day. When these diluted medicines were added, all
      caused relaxations in a concentration-dependent manner. The percentages of (max
      B/max A) x 100 were: Gorei-san, 41 +/- 14 (%) (n = 6, mean +/- SD); Saiko-keishi
      to, 37 +/- 18% (n = 6); Ryokei-jutsukan-to, 26 +/- 16% (n = 6); and Shokenchu-to,
      10 +/- 5% (n = 6). Compared to the control group which did not receive Chinese
      medicines, drugs I, II and III showed statistically significant relaxation
      effects (p < 0.05). The amount of relaxation caused by these medicines (I-III)
      was 1/3-1/4 of the relaxation caused by a cholinergic antagonist, cyclopentlate
      (10(-5)M). The results suggest that Chinese medicines (I-III) produce moderate
      relaxation of ciliary muscles.

PMID- 7825499
TI  - [Analysis of electrically evoked response in relation to the central pathway of
      the cat (3). Current source density analysis in area 17 of cats].
AB  - We analyzed current source density and multiple unit activity of area 17 of cats
      in response to transcorneal electrical stimuli to clarify the localization of the
      transmembrane current flows contributing to the generation of the electrically
      evoked response. The results of the current source density analysis were as
      follows. 1. Current sinks within 20 ms were observed in layers 4 and 6. 2.
      Current sinks corresponding to N3 (latency 35 ms) were detected in layers 4 and
      lower 3 and current sources were in the supragranular layers. 3. Current sinks
      with a latency of more than 40 ms were observed in the supragranular layers.
      Simultaneous multiple unit activity was present in cases 1 and 2. With increased
      stimulus frequency or double electrical stimuli, the current sinks corresponding
      to N3 were decreased. These findings indicate that N1 (latency 9 ms) and N2
      (latency 20 ms) reflect near-field potentials generated by geniculocortical
      afferents in layers 4 and 6, and that N3 is a post-and polysynaptic component. In
      addition, it appears that dipoles consisting of cell bodies and apical dendrites
      of pyramidal cells in layer 3 generated by satellite cell in layer 4, play a
      major role in generating N3.

PMID- 7825500
TI  - [Effect of UF-021 on optic nerve head circulation in rabbits].
AB  - We studied the effect of UF-021, a prostaglandin-related compound under
      application as an anti-glaucoma agent, on the circulation of the optic nerve head
      (ONH) in normal and endothelin-1 treated albino rabbit eyes. Measurement of the
      capillary blood flow in the ONH with a hydrogen gas clearance flowmeter as well
      as intraocular pressure (IOP) measurement was done for five hours. Instillation
      of UF-021 reduced IOP (maximum: 3.7 mmHg) but had no significant effect on the
      ONH blood flow in normal eyes. Intravitreal injection of UF-021 reduced IOP to
      less extent (maximum: 1.8 mmHg) and significantly increased the ONH blood flow
      (maximum increment: 14% of initial value) from 1 hour to 3.5 hours after
      injection in normal eyes. In model eyes of circulatory disorder, UF-021 did not
      affect IOP but inhibited the decrease in the ONH blood flow at 2.5 and 3.5 hours
      after administration. These results indicate that the effect of UF-021 on ONH
      circulation is favorable because its blood flow is maintained.

PMID- 7825501
TI  - [Intraocular penetration of oral levofloxacin in rabbits].
AB  - The intraocular penetration of levofloxacin was studied in albino and pigmented
      rabbits after oral administration of 14C-levofloxacin at a dose of 20 mg/kg. The
      radioactivity of the eyeball of albino rabbits in the autoradiogram was much
      higher at 1 hr than at 2 or 6 hr after administration. On the other hand, the
      distribution of radioactivity in pigmented rabbits was similar at 1, 2, and 6 hr
      after administration. The radioactivity levels in melanin-containing tissues such
      as the iris-ciliary body and the choroid-retina were significantly higher in
      pigmented rabbits than in albino rabbits 2 hr after oral administration. The
      radioactivity levels in the ocular tissues without melanin except for the cornea
      were similar in albino and pigmented rabbits. These results indicate that the
      intraocular pharmacokinetics of levofloxacin are markedly affected by its
      affinity for melanin.

PMID- 7825502
TI  - [The retinal image of three multifocal intraocular lenses through an eye model].
AB  - Retinal images produced by two types of multifocal intraocular lenses (IOLs) were
      studied using an eye model. One of them was a refractive IOL with five zones, and
      the other was a diffractive lens. The IOLs were inserted into an eye model with a
      pupil diameter of 3 mm. The retinal plane of the eye model was observed
      microscopically. When the section of the IOL used for far vision was in focus,
      the retinal image of the refractive IOL was almost the same as that of the
      monofocal IOL, which was better than that of the diffractive IOL. When the near
      vision section of the IOL was in focus, the retinal image of the diffractive IOL
      had almost the same quality as the far section. The light rings produced when the
      multifocal IOLs were illuminated by a glare source were also examined. They
      showed that the diffractive IOL was stronger than the refractive IOL, but the
      monofocal was the smallest of the three.

PMID- 7825503
TI  - [Multivariate analysis of risk factors of rejection in penetrating keratoplasty].
AB  - In order to evaluate preoperative risk factors that affect the incidence of
      endothelial rejection after penetrating keratoplasty, we performed statistical
      analysis on 571 consecutive cases who had been followed at the University of
      Tokyo Hospital for at least one year. We applied a logistic regression model
      (multiple variate analysis) to determine the significance of the association
      between the preoperative factors and the incidence of rejection. We identified
      four preoperative risk factors of endothelial rejection in a year as follows: the
      extent of corneal vascularization, failed previous graft continuous sutures, and
      preoperative corneal endothelial damage. When the rejection cases were divided
      into an early group that suffered rejection within 3 months and a late group that
      suffered rejection after 6 to 12 months, young patients were likely to suffer
      rejection in the early postoperative period.

PMID- 7825504
TI  - [Spectral transmittance of normal human crystalline lens].
AB  - The spectral transmittance and non-tryptophan fluorescence of human crystalline
      lenses were evaluated. Eleven eye bank lenses and three lenses of prematurity of
      retinopathy patients were investigated. All lenses absorbed the short wavelength
      light below 430 nm strongly. The transmission of the short wavelength visible
      light decreased gradually with age. There was a positive correlation between the
      fluorescence intensity ratio of non-tryptophan to tryptophan fluorescence and the
      logarithm of age. It was thought that the generation of non-tryptophan
      fluorescence might be a first-order chemical reaction.

PMID- 7825505
TI  - [Safety and ocular hypotensive effect of a new prostaglandin analogue, S-1033, in
      normal volunteers].
AB  - We conducted a prospective, placebo-controlled, double-masked study to
      investigate the ocular hypotensive effect and safety of a new prostaglandin
      analogue, S-1033, in healthy human volunteers. In a single-dose, dose-finding
      study, where 0.1%, 0.2%, 0.3%, or 0.4% of S-1033 and the vehicle ophthalmic
      solution was instilled in each one eye of six adult male volunteers and vehicle
      solution alone in the fellow eye, 0.3% solution showed a significant ocular
      hypotensive effect at 1, 2, and 8 hours following the instillation and 0.4%
      solution showed a similar effect at 4 hours after the instillation. The following
      multiple-dose study, where 0.3% S-1033 solution was instilled twice daily for 8
      days in one eye of six volunteers and the vehicle in the follow eye, revealed a
      significant, continuous intraocular pressure (IOP) reduction. Mild, transient
      conjunctival hyperemia and slight ocular discomfort developed in some cases, but
      they were minor. These results indicate that S-1033 has a significant ocular
      hypotensive effect without substantial adverse effects and the new compound seems
      to deserve further investigation as a possible anti-glaucoma medication.

PMID- 7825506
TI  - [Analysis of ophthalmic arterial flow by color Doppler imaging in glaucomatous
      eyes].
AB  - The blood flow velocity of the ophthalmic artery was analyzed by color Doppler
      imaging in normal subjects and patients with primary open-angle glaucoma (POAG)
      or normal-tension glaucoma (NTG), to investigate the changes in intraocular
      circulatory dynamics. Maximum systolic flow velocity (Vmax), minimum diastolic
      flow velocity (Vmin), time-averaged flow velocity (Vmean), and resistivity index
      (RI) were determined. The coefficients of variation as indices for the
      reproducibility of the measurements in five normal volunteers were 5.0 +/- 4.0%,
      8.8 +/- 5.7%, 7.9 +/- 7.5%, and 2.3 +/- 1.9% (mean +/- SD) for Vmax, Vmin, Vmean
      and RI. Measurements of ophthalmic arterial flow velocity were made in 20
      patients with POAG, 20 patients with NTG, and 30 normal subjects matched for mean
      age. The POAG patients and NTG patients showed a significant reduction in the
      three indices for velocities (p < 0.01) and a significant increase in RI (p <
      0.05) compared with normal subjects. There were no significant differences in all
      the four indices between POAG and NTG in patients matched for similar visual
      field defects and mean age. Our results indicate that the circulatory dynamics of
      the ophthalmic artery were different in glaucoma patients than in normal
      subjects.

PMID- 7825507
TI  - [Influence of refraction on the visual field defects in normal tension glaucoma
      and primary open angle glaucoma eyes].
AB  - The prevalence of normal tension glaucoma (NTG) or primary open angle glaucoma
      (POAG) is higher in myopic populations and the prevalence of myopia and NTG is
      relatively high in the Japanese. To evaluate the influence of myopic refractive
      error on the central visual field defect in NTG eyes, the data obtained from NTG
      eyes with the Humphrey Visual Field Analyser were analysed in comparison with
      those from POAG eyes. One hundred and twenty NTG eyes and one hundred and ninety
      seven POAG eyes were included. All of them had clear ocular media, but no myopic
      degeneration in the fundus. Multiple linear regression analysis was performed
      with a dependent variable of the deviation of the measured threshold value from
      normal reference value (total deviation, STATPAC) and independent variables of
      refractive error and mean deviation (STATPAC). Myopic power was found to be
      positively correlated with the depression in the lower papillo-macular area in
      both NTG and POAG eyes, and it was negatively correlated with the depression in
      an upper arcuate area extending just nasal to the fixation only in NTG eyes.

PMID- 7825508
TI  - [A study of the relationship between diabetic neuropathy and diabetic
      retinopathy].
AB  - To evaluate the relationship between diabetic neuropathy and retinopathy, we
      examined autonomic nervous function, postural hypotension, nerve conduction
      velocity and coefficient of variation of R-R intervals. Forty-five non-insulin
      dependent diabetic cases were classified as no diabetic retinopathy (group A),
      simple diabetic retinopathy (group B) and proliferative diabetic retinopathy
      (group C). These groups did not differ in age or gender. The rate of postural
      hypotension (depression of systolic blood pressure over 30 mmHg) was 0% in group
      A, 7% in group Bs and 53% in group C. Nerve conduction velocity in both motor and
      sensory nerve was delayed over 20% in 0% of group A, 8% of group B, and 33% of
      group C. In CVR-R, 11% of group A and 7% of group B were decreased, and 44%
      (during rest) and 33% (during deep breathing) of group C was decreased. Between
      groups A and B there was no statistical difference. But group C had statistically
      significant difference from other groups, particularly in postural hypotension.
      Peripheral neuropathy might be closely related to diabetic retinopathy.

PMID- 7825510
TI  - [A case of uveitis due to gnathostoma migration into the vitreous cavity].
AB  - We report a 26 year-old male patient who had floaters and hyperemia in his left
      eye following uveitis due to gnathostoma that had migrated into the vitreous
      cavity. Severe iridocyclitis and mild opacity of the vitreous body were observed,
      together with whitish-yellow subretinal tracks accompanied by dot and blot
      hemorrhages in the fundus. Slit lamp microscopic examination revealed a worm
      which writhed in the vitreous cavity. We performed vitrectomy to remove the worm
      from the anterior vitreous uneventfully, followed by prompt subsidence of the
      inflammatory signs. The worm was identified as a third instar larva of
      Gnathostoma doloresi. Eosinophilia and creeping eruption did not appear
      throughout the follow-up period. The patient was accustomed to eat live roaches
      and whitebait, as well as sliced raw beef liver.

PMID- 7825509
TI  - [Visual function in patients with optic neuritis associated with acute transverse
      myelopathy in multiple sclerosis].
AB  - We reviewed the records of 20 patients with optic neuritis who were diagnosed to
      have clinically definite multiple sclerosis (MS). We classified them into 2
      subgroups: group A, consisting of 9 patients who had acute transverse myelopathy
      (ATM); and group B, 11 patients without ATM. 4 patients (44%) in group A had
      complete visual loss, but none in group B. 6 patients (67%) in group A had less
      than 0.1 visual acuity in the affected eye, but only 2 patients (18%) in group B.
      4 patients in group A had evidence of anticardiolipin antibodies. While both
      groups were diagnosed as having clinically definite MS, there were differences in
      the clinical features between them. We assume that the patients with ATM
      constitute a different subgroup among MS patients.

PMID- 7825511
TI  - [Rapidly progressive outer retinal necrosis in a patient with acquired
      immunodeficiency syndrome].
AB  - We report a case of rapidly progressive varicella zoster virus retinitis, which
      is distinct from acute retinal necrosis syndrome. The patient was a 52-year-old
      male and suffered acquired immunodeficiency syndrome. Two months after the
      varicella zoster dermatitis in the distribution of the first division of the left
      trigeminal nerve, pseudodendritic keratitis and iridocyclitis were observed in
      the left eye. After 5 weeks, multifocal and patchy white exudates were observed
      in the peripheral deeper layer of the retina in the left eye, but retinal
      vasculitis in the exudative lesions was slight. Despite systemic administration
      of acyclovir, white exudates progressed confluently from the periphery to the
      post pole of the retina and reached the macula in 10 weeks. Eight weeks after the
      observation of lesions in the left eye, we found the same lesions in the right
      eye. After the white exudative lesions disappeared, the retina became atrophic
      and the retinal vessels were narrowed, but no retinal detachment was observed.
      Recently, Foster and associates described the rapidly progressive outer retinal
      necrosis as a new entity of varicella zoster virus retinitis in AIDS patients. We
      think our case was very similar to the rapidly progressive outer retinal
      necrosis. This case shows that we must carefully follow up the rapidly
      progressive outer retinal necrosis in the AIDS patients with a varicella zoster
      dermatitis.

PMID- 7825512
TI  - [Early cytomegalovirus retinitis].
AB  - We report the clinical course of cytomegalovirus (CMV) retinitis associated with
      acquired immunodeficiency syndrome (AIDS) from the initial onset. The patient was
      a 40-year-old human immunodeficiency virus antibody-positive male with hemophilia
      A. He was diagnosed as having AIDS on the basis of pneumocystis carinii
      pneumonia. Ophthalmoscopic examination disclosed a small white punctate lesion at
      the macular area in his right eye. Because the lesion enlarged gradually with
      hemorrhages, it was suspected to be CMV retinitis. However, further examination
      was impossible due to his severe general condition. He died five months later and
      the autopsy disclosed disseminated CMV infection. Ocular histopathological
      examination revealed CMV retinitis. The earliest sign of CMV retinitis is
      supposed to be a white punctate retinal lesion, which becomes a small white
      patchy lesion resembling a cotton-wool spot. It may gradually progress to diffuse
      retinal involvement, frequently associated with hemorrhages.

PMID- 7825513
TI  - Evaluation of optical source-detector configurations for tomographic
      reconstruction of chemical concentrations in indoor air.
AB  - This article reports on numerical studies to evaluate and compare optical remote
      sensing configurations for tomographically reconstructing pollutant
      concentrations in indoor air. With a remote sensing/computed tomography system,
      two-dimensional maps of pollutant concentrations with good spatial resolution can
      be created for an entire room. The successful use of such a system for exposure
      assessment, ventilation assessment, or source monitoring depends on the remote
      sensing configuration. A systematic method was developed to evaluate the
      performance of 10 configurations. One hundred and twenty test maps were
      reconstructed with an algebraic reconstruction method using all 10
      configurations; reconstruction quality was evaluated using 4 criteria.
      Reconstruction quality was related to the number and location of detectors in the
      room and the complexity of the test maps. Configurations using the same number of
      detectors placed in different locations resulted in reconstructions that differed
      in quality. The effect of reducing the number density of rays on reconstruction
      quality was studied. Based on these simulations, two configurations that used
      four detectors to scan the room were selected, and their performance was
      evaluated in the presence of various levels of measurement noise. Two
      configurations that used four detectors were most suited for exposure assessment.
      It was found that when designing a configuration, the number and independence of
      rays should be maximized. Results underscored the need to thoroughly test
      configurations through numerical studies prior to field implementation; a wide
      variety of concentration maps, relevant to the application, should be tested
      under both ideal and nonideal sampling conditions.

PMID- 7825514
TI  - Personnel protection during aerosol ventilation studies using radioactive
      technetium (Tc99m)
AB  - Two commercially available nebulizing devices used for ventilation studies were
      evaluated. The nebulizers use radioactive Technetium-99m (Tc99m), a potential
      source of room air contamination. Ambient air concentrations of Tc99m were
      monitored, as were the exposures of department personnel not performing
      ventilation studies. Room surfaces and air vents were examined to determine the
      extent of contamination in the examination room. Personnel were evaluated for
      contamination on clothing, hair, and airways when hospital lab coats and latex
      gloves were the only protective apparel used. Though the maximum permissible
      concentration of 4 x 10(-5) microCi/c3 was not exceeded, preliminary results
      indicated levels as high as 11,000 disintegrations/min in the nasal passages of
      personnel. These findings clearly demonstrate the need for more effective
      personal protective devices. Personnel contamination resulted primarily from the
      patient, due to an inability to maintain a proper oral seal on the nebulizer
      mouthpiece. Conventional hospital surgical masks were ineffective in reducing
      internal deposition to tolerable levels. By comparison, levels were reduced by
      19% (p > 0.10) through use of methods such as simple body substance isolation
      techniques and high-efficiency disposable respirators. Levels approaching 50
      disintegrations/min or less were obtainable (p < 0.001), and overall levels of
      Tc99m were reduced by 78%.

PMID- 7825515
TI  - Personal exposure to pesticide among workers engaged in pesticide container
      recycling operations.
AB  - Pesticide container handling operations in western Canada were examined to
      determine the exposure of workers to residual pesticide in sorting, metal
      container crushing, metal-container shredding, plastic-container shredding, metal
      washing, and metal melting. Environmental exposure monitoring and biological
      monitoring were applied, including measurement of pesticide deposition density on
      outer clothing (test coveralls and other protective wear), deposition on fabric
      and gauze patches under the outer clothing, inhalation of airborne pesticide
      residues, dislodgement of pesticide residues by hand washing, and pre- and
      postexposure urinary excretion of pesticide (2,4-D). Exposure levels were highly
      variable; some variability was accounted for by work practices or lapses in
      protection. The highest levels of exposure were observed for metal washing, metal
      crushing, and metal shredding; sorting and plastic shredding were intermediate,
      and metal melting was associated with very little exposure. Urinary 2,4-D
      excretion, as an indicator of internal dose, correlated most closely with
      exposure by the inhalation route, and both were highest for metal washing and
      shredding. Deposition of pesticide on garments was highest for metal crushing.
      Melting of washed metal does not appear to present a significant hazard of
      exposure. Recommendations are proposed for the protection of workers emphasizing
      health and safety guidelines, worker education, personal hygiene, exposure and
      health monitoring, and record-keeping, and specific recommendations for each
      process. These recommendations apply to all pesticide container recycling
      operations except melting of washed metal containers.

PMID- 7825516
TI  - Whole-body vibration exposure: a comprehensive field study.
AB  - A comprehensive field study investigated whole-body vibration exposure levels
      experienced by the train operators of a large metropolitan subway system. The
      purposes of the study were to measure mechanical vibrations transmitted to the
      seated train operators, to calculate daily whole-body vibration exposure levels,
      and to compare these levels with maximum acceptable exposure levels recommended
      by the international standard on whole-body vibration (ISO 2631). The study also
      sought to identify factors that may influence mechanical vibrations transmitted
      to the operators and quantify their effects on the measured vibration levels. The
      study was carried out by dividing the subway system into subway lines, each line
      into southbound and northbound directions, and each direction into station-to
      station observations. Triaxial measurements were made on all subway lines and for
      all car types used in the system. For each line, at least two round trips of data
      were collected. Time-weighted averages of the two sets of data were used for
      final presentation. A total of 48 round trips were made and more than 100 hours
      of vibration data was collected and analyzed. All phases of the study were
      carried out in accordance with the procedures outlined in ISO 2631. It was
      determined that 6 out of 20 subway lines had vibration levels higher than daily
      exposure limits recommended by ISO 2631. It was also determined that train speed
      was the most significant factor influencing vibration exposure levels.

PMID- 7825518
TI  - A bibliography for occupational exposure assessment for epidemiologic studies.

PMID- 7825517
TI  - A sampling and analytical method for the simultaneous determination of multiple
      organophosphorus pesticides in air.
AB  - A sampling and analytical method for organophosphorus pesticides using a combined
      filter/XAD-2 sorbent sampler and gas chromatography (GC)-flame photometric
      detection (FPD) was developed. The method was evaluated for 19 organophosphorus
      pesticides based on the joint Occupational Safety and Health
      Administration/National Institute for Occupational Safety and Health Standards
      Completion Program methods evaluation protocol. The evaluation addressed analyte
      recovery, sampler capacity, sample stability, and precision and accuracy.
      Additional experiments addressed long-term sample stability (30-day storage),
      short-term exposure limits, limits of detection, and concentration levels down to
      0.1 times an exposure limit value. Samples were stable for 30 days of storage
      under either ambient or refrigerated conditions. Based on this research, all 19
      compounds studied can be successfully determined simultaneously using one method
      with an accuracy of +/- 25% of the true value 95 times out of 100.

PMID- 7825519
TI  - Copper deficiency: interaction with high-fructose and high-fat diets in rats.
AB  - The purpose of this study was to investigate whether a high fat intake would
      potentiate an excess of fructose in the diet of rats to alter energy metabolism
      and worsen the nutritional status for copper. Weanling male rats were fed diets
      with 45% fat and 20% cornstarch, 45% fat and 20% fructose, 5% fat and 60%
      cornstarch, or 5% fat and 60% fructose for 3 wk, with either sufficient (+) or
      deficient (-) amounts of copper. Copper deficiency, as demonstrated by low plasma
      copper and ceruloplasmin, caused a decrease of liver, heart, and testes copper; a
      decline of liver and heart zinc; and an increase of hepatic iron. High-fat diets
      reduced liver glucose-6-phosphate dehydrogenase (G6PDH) and, to a lesser extent,
      glycerophosphate dehydrogenase (GPDH). The interaction between high-fat and high
      fructose diets, superimposed on copper deficiency, resulted in a lowering of
      G6PDH, GPDH, and malic enzyme. These results support the hypothesis that a high
      fat ingestion becomes an aggravating stress factor, which, in combination with a
      high-fructose intake in a copper-deficient diet, adversely alters key organ
      mineral content, with detrimental effects on copper nutritional status and
      intermediary metabolism.

PMID- 7825520
TI  - Proportion of energy intake from fat and subsequent weight change in the NHANES I
      Epidemiologic Follow-up Study.
AB  - We examined the association of percent energy intake from fat with subsequent
      weight change in 2580 men and 4567 women, using data from the National Health and
      Nutrition Examination Survey (NHANES) I Epidemiologic Follow-up Study (NHEFS).
      Weight change was defined as the difference between the follow-up weight (NHEFS,
      1982-1984) and the baseline weight (NHANES I, 1971-1974). Fat intake was
      estimated from a 24-h dietary recall obtained at baseline. Regression analyses
      adjusted for potential confounders showed no significant association of percent
      fat energy with weight change in men. Among women aged < 50 y, the inverse
      relation of percent fat energy with weight change was significant (beta = -0.052,
      P = 0.04). After exclusion of respondents with any morbidity from the analytic
      cohort, percent fat energy and weight change were positively associated in men
      (beta = 0.046, P = 0.05), but not in women. In conclusion, percent fat energy
      intake and weight change were inversely related in women aged < 50 y in the NHEFS
      cohort, but positively associated in men without any morbidity.

PMID- 7825521
TI  - Effect of daily vs twice weekly iron supplementation in Indonesian preschool
      children with low iron status.
AB  - The effect of daily vs twice weekly iron supplementation on iron status was
      studied in preschool children with low iron status in a randomized double-masked
      field trial. Subjects (n = 87) were selected on the basis of their hemoglobin
      concentration being < 111 g/L in finger-prick blood, and were divided into two
      groups. For 8 wk one group received a daily supplement of 30 mg Fe, while the
      other group received 30 mg Fe twice per week. A complete data set was obtained
      from 32 children in the group supplemented daily and from 33 children in the
      group supplemented twice weekly. Hemoglobin, serum ferritin, and protoporphyrin
      increased significantly in both groups (P < 0.001). Changes in hemoglobin and
      protoporphyrin were correlated with initial hemoglobin concentration (P < 0.001).
      The difference in treatment effect between groups was not significant after
      correction for the initial hemoglobin concentration. It is concluded that in
      preschool children with low iron status, twice weekly iron supplementation has an
      effect on iron status similar to that of daily supplementation.

PMID- 7825522
TI  - IGF-I alters energy expenditure and protein metabolism during parenteral feeding
      in rats.
AB  - In this study, 20 micrograms.kg.-1.h-1 of recombinant human insulin-like growth
      factor I (IGF-I) was infused into normal healthy rats to examine the effects of
      IGF-I on glucose, protein, and energy metabolism in either overnight-fasting or
      parenteral-feeding states. The fed state was maintained by continuous intravenous
      feeding of a complete diet containing 838 kJ.kg-1.d-1, 2 g N.kg-1.d-1, and no
      fat. At each nutritional state, one-half of the animals received IGF-I infusion
      while the other half received saline as control. [14C-1]leucine and [3H-6]glucose
      were used to determine the effects of IGF-I on protein and glucose kinetics
      during fed and fasting states. The results showed that 1) infusion of IGF-I at
      this amount did not alter plasma glucose appearance and only marginally decreased
      plasma glucose concentrations in both nutritional states; 2) during fasting, IGF
      I did not show anabolic effects on protein metabolism either at the whole-body
      level or in individual tissues. However, during feeding, IGF-I significantly
      stimulated exogenous nitrogen utilization by the whole body; and 3) IGF-I reduced
      the thermogenic effect of feeding. The results suggest that parenteral feeding
      may be an important variable in the response of protein anabolism to IGF-I in
      vivo.

PMID- 7825523
TI  - Dietary supplementation with n-3 fatty acids increases gluconeogenesis from
      glycerol but not hepatic glucose production in patients with non-insulin
      dependent diabetes mellitus.
AB  - Fish-oil supplementation decreases serum triacylglycerols but may worsen
      hyperglycemia in patients with non-insulin-dependent diabetes mellitus. The
      reason for the possible deterioration of glycemia is unclear. We examined whether
      inhibition of triacylglycerol synthesis by n-3 fatty acids changes lipolysis,
      glycerol gluconeogenesis, or fatty acid oxidation. Nine obese patients with non
      insulin-dependent diabetes mellitus participated in a randomized double-blind
      crossover study in which 6 wk of n-3 fatty acid supplementation (12 g fish oil)
      was compared with 6 wk of corn plus olive oil. Serum triacylglycerols decreased
      by 30% during n-3 fatty acid supplementation. Glycerol gluconeogenesis ([U
      14C]glycerol) increased by 32%. However, overall glucose production ([3
      3H]glucose), glycemic control, and fatty acid oxidation remained unchanged. Thus,
      6 wk of n-3 fatty acid supplementation lowers triacylglycerols in patients with
      non-insulin-dependent diabetes mellitus without worsening glycemic control.
      However, n-3 fatty acid supplementation increases glycerol gluconeogenesis, which
      could contribute to deterioration of glycemic control during long-term treatment
      with high doses of fish-oil supplements.

PMID- 7825525
TI  - Mycoprotein reduces glycemia and insulinemia when taken with an oral-glucose
      tolerance test.
AB  - This study investigated the effects of mycoprotein, a food produced by the
      continuous fermentation of Fusarium graminearum (Schwabe), on acute glycemia and
      insulinemia in normal healthy individuals. Subjects participated in two single
      meal study periods in a crossover design. After an overnight fast, subjects were
      given milkshakes containing mycoprotein or a control substance, which were
      isoenergetic and nutrient balanced. Each milkshake contained 75 g carbohydrate,
      equivalent to a standard World Health Organization oral-glucose-tolerance test.
      Blood samples were taken fasting and at 30, 60, 90, and 120 min postprandially
      for the measurement of serum glucose and insulin. Glycemia was reduced postmeal
      after mycoprotein compared with the control and was statistically significant at
      60 min (13% reduction). Insulinemia was reduced postmeal after mycoprotein
      compared with the control and was statistically significant at 30 min (19%
      reduction) and 60 min (36% reduction) postmeal. These results may be significant
      in the dietary treatment of diabetes.

PMID- 7825524
TI  - Guar gum effects on plasma low-density lipoprotein and hepatic cholesterol
      metabolism in guinea pigs fed low- and high-cholesterol diets: a dose-response
      study.
AB  - Guinea pigs were fed semipurified diets containing either 0% or 12.5% guar gum
      (GG) with 0.04% cholesterol or increasing concentrations of GG (0%, 2.5%, 5%,
      7.5%, 10%, and 12.5%) with 0.25% cholesterol (by wt). Compared to the 0% GG diet
      with 0.04% cholesterol, intake of the 12.5% GG diet with 0.04% cholesterol
      lowered plasma low-density-lipoprotein (LDL) concentrations, the ratio of LDL
      cholesteryl ester to protein, hepatic cholesterol concentrations, and the
      activity of acyl-CoA:cholesterol acyltransferase (ACAT), and increased 3-hydroxy
      3-methylglutaryl coenzyme A (HMG CoA) reductase activity and hepatic apo B/E
      receptor number (P < 0.01). Intake of GG by animals fed 0.25% cholesterol diets
      resulted in modest effects on hepatic cholesterol pools and plasma LDL
      concentrations; however, significant negative correlations were found between
      both plasma LDL cholesterol and hepatic free cholesterol concentrations with the
      amount of dietary GG (P < 0.05). Hepatic HMG-CoA reductase was suppressed by the
      0.25% cholesterol intake, and GG did not reverse this suppression. In contrast,
      ACAT activity was negatively correlated with the amount of dietary GG (P < 0.05),
      and GG intake increased the number of hepatic apo B/E receptors at all intakes
      with the 0.25% cholesterol diets. These results demonstrate that intake of GG
      significantly alters endogenous cholesterol metabolism by decreasing hepatic
      cholesterol pools, altering hepatic cholesterol homeostasis, and reducing plasma
      LDL concentrations.

PMID- 7825526
TI  - Effect of apolipoprotein E polymorphism on the serum lipid response to a
      hypolipidemic diet rich in monounsaturated fatty acids in patients with
      hypercholesterolemia and combined hyperlipidemia.
AB  - We investigated the effect of variation at the apolipoprotein (apo) E gene locus
      on the serum lipid response to a hypolipidemic diet rich in monounsaturated fatty
      acids (MUFA). Lipoprotein changes were assessed in 122 outpatients with type IIa
      (n = 70) and type IIb (n = 52) hyperlipidemia [80 men and 42 women with apo E
      phenotypes 3/2 (n = 27), 3/3 (n = 48), and 4/3 (n = 47)] who were switched from
      their basal diet containing 40% fat (22% MUFA) to an isoenergetic diet containing
      31% fat (MUFA content similar to that of the basal diet) for 12 wk. Significant
      (P < 0.005) reductions of total, LDL, and VLDL cholesterol; triglycerides; and
      apo B occurred in subjects regardless of WHO phenotype. Triglycerides and VLDL
      cholesterol decreased more in type IIb than in type IIa subjects: 25% vs 12% and
      21% vs 15%, respectively (P = 0.01). HDL cholesterol tended to decrease only in
      women. The heterogeneity of lipoprotein responses to dietary intervention was
      unrelated to apo E phenotypes. In these hyperlipidemic subjects, however, diet
      induced favorable changes in serum lipoproteins were selectively influenced by
      WHO phenotype.

PMID- 7825527
TI  - Effects of cafestol and kahweol from coffee grounds on serum lipids and serum
      liver enzymes in humans.
AB  - The diterpenes cafestol and kahweol are present in unfiltered coffee in oil
      droplets and floating fines. They elevate serum cholesterol and alanine
      aminotransferase (ALT). We measured fines in coffee brews, and examined diterpene
      availability from spent grounds in healthy volunteers. Turkish or Scandinavian
      boiled coffee contained 2-5 g fines/L and French press coffee contained 1.5 g
      fines/L. An intake of 8 g fine grounds/d for 3 wk increased cholesterol by 0.65
      mmol/L (95% CI 0.41-0.89 mmol/L) and ALT by 18 U/L (95% CI 4-32 U/L) relative to
      control subjects (n = 7/group). In a crossover study (n = 15), mean serum
      cholesterol was 4.9 mmol/L after consumption of both fine and coarse grounds for
      10 d (P = 0.43). Serum ALT activities were 29 U/L on fine and 21 U/L on coarse
      grounds (P = 0.02). Floating fines could contribute substantially to the
      hyperlipidemic and ALT-elevating effect of unfiltered coffee. Diterpene
      measurements in coffee brews should include the contribution of fines.

PMID- 7825528
TI  - Sample-size implications for population-based cluster surveys of nutritional
      status.
AB  - We studied the design effects for population-based surveys that estimated the
      prevalence of wasting and stunting malnutrition in Malawi, Zambia, Indonesia, and
      Nepal, and studied the magnitude of different types of malnutrition clustering
      within villages. Weight, height, and midupper-arm circumference were measured on
      all children or on systematic samples of children in randomly selected villages.
      Design effects ranged from 0.53 for low height-for-age in Zambia to 6.12 for low
      weight-for-age in Nepal. If all sampled clusters were of size 30, as is often the
      case for nutrition surveys, design effects would have ranged from 0.44 for low
      height-for-age in Zambia to 2.59 for low midupper-arm circumference in Zambia.
      Malnutrition did cluster within villages. Stunting malnutrition clustered less
      than did wasting malnutrition. Nutrition surveys using clusters of 30 can sample
      fewer clusters than currently recommended if basic prevalence and cluster
      information are available prior to sample selection.

PMID- 7825529
TI  - Nutrition education in medical schools: a Canadian experience.

PMID- 7825530
TI  - Tumor necrosis factor and AIDS.

PMID- 7825531
TI  - Potential complication of multivitamin use in patients with Wilson's disease.

PMID- 7825532
TI  - Increased liver carnitine content in obese women.
AB  - In experimental animals the enhancement of hepatic fatty acid oxidation and
      ketogenic capacity is accompanied by a rise in the concentration of liver
      carnitine. Massive obesity is characterized by enhanced fatty acid turnover,
      insulin resistance, and often a fatty liver. Carnitine concentrations were
      determined in liver, abdominal muscle tissue, and blood in morbidly obese women.
      The liver and muscle carnitine concentrations were significantly higher in the
      obese subjects than in the lean control subjects. These findings suggest an
      increase of the whole-body carnitine pool. In the obese subjects there was also a
      significant positive correlation between liver and muscle carnitine
      concentrations. In the majority of the obese subjects fatty changes could be
      demonstrated in the liver. The plasma insulin concentration tended to be
      positively correlated with the degree of fat infiltration and negatively
      correlated with the liver carnitine content. It is concluded that the liver
      carnitine content is significantly increased in obese women, which agrees with
      the finding in experimental animals.

PMID- 7825533
TI  - Validity and epidemiology of reported poor appetite among Peruvian infants from a
      low-income, periurban community.
AB  - To assess the validity of maternal reports of poor infant appetite, these
      histories were compared with measured energy consumption on 1621 d of observation
      of 131 Peruvian infants in a low-income community. Mean (+/- SD) total energy
      intakes on days with reported anorexia were 338 +/- 88 kJ/kg body wt in infants 1
      6 mo of age and 299 +/- 92 kJ/kg body wt in infants aged > 6 mo compared with 395
      +/- 92 and 342 +/- 88 kJ/kg body wt in the respective age groups when appetites
      were reportedly normal (P < 0.001). Energy intake from non-breast-milk sources
      was more affected than energy from breast milk. The epidemiology of poor appetite
      was assessed in 153 infants who were monitored longitudinally during their first
      year of life. The prevalence of reported anorexia increased progressively from 22
      to 317/1000 d of observation from < 1 to 11 mo of age. Infant age and the
      presence of fever, diarrhea, and respiratory illnesses were each associated
      negatively with the presence of reduced appetite. Poor appetite, rather than lack
      of food, may explain in part the low energy intakes by infants in this community.

PMID- 7825534
TI  - Whole-body protein turnover in elderly men and women: responses to two protein
      intakes.
AB  - In this study the effect of protein intake (12% and 21% of total energy intake,
      diets A and B, respectively) on nitrogen balance and on whole-body protein
      turnover (PT) was measured in 17 elderly men and 11 elderly women (mean +/- SD:
      74 +/- 12 y and 68 +/- 9 y, respectively) with different levels of physical
      activity. Mean (+/- SD) nitrogen balance (diet A: -0.004 +/- 0.027 g.kg-1.d-1,
      diet B: 0.011 +/- 0.064 g.kg-1.d-1) did not differ significantly from zero during
      either diet. PT increased significantly when the protein content of the diet
      increased from 12% to 21% of total energy (P < 0.0001). There was a positive
      correlation between protein intake and PT (diet A: synthesis and breakdown, P <
      0.01; diet B: synthesis, P < 0.001; breakdown, P < 0.0001). PT rates were
      significantly higher for men when compared with women, even when corrections were
      made for differences in body composition (P < 0.05).

PMID- 7825535
TI  - Energy intakes are higher during the luteal phase of ovulatory menstrual cycles.
AB  - We compared energy and macronutrient intakes across the menstrual cycle in
      participants (n = 42) in a study that assessed the frequency of ovulatory
      disturbances in regularly cycling vegetarians and nonvegetarians. Women kept
      daily basal body temperature records for six consecutive menstrual cycles and
      provided 3-d diet records near the beginning, middle, and end of different
      cycles. On completion of the study, temperature records were quantitatively
      analyzed to determine whether cycles were ovulatory, and if so, the date the
      luteal phase began. Diet records kept near the beginning and end of cycles were
      matched with temperature analysis results, and women were grouped according to
      whether the end-of-cycle record was kept during the luteal phase of an ovulatory
      cycle (group 1, n = 29), or during an anovulatory cycle or before luteal phase
      onset of a short luteal phase cycle (group 2, n = 13). Group 1 had higher energy
      intakes during the luteal than during the follicular phase (9.27 +/- 2.69 vs 8.01
      +/- 2.36 MJ/d, P < 0.0001), whereas intakes of group 2 did not differ across the
      cycle (7.91 +/- 2.18 vs 8.20 +/- 1.48 MJ/d, NS). Both groups' macronutrient
      intakes were similar in records kept near the beginning and end of cycles.
      Documentation of ovulation is necessary in studies assessing premenopausal
      women's energy intakes.

PMID- 7825536
TI  - Influence of body composition and resting metabolic rate on variation in total
      energy expenditure: a meta-analysis.
AB  - The influence of body composition, resting metabolic rate (RMR), and sex on
      variation in total energy expenditure (TEE) was examined by using meta-analysis
      (13 published studies in a total of 162 adults). TEE (10.9 +/- 3.2 MJ/d) was
      significantly correlated with body mass (BM; weighted mean converted r = 0.68, P
      < 0.05) and resting metabolic rate (RMR; weighted mean converted r = 0.66, P <
      0.05). The correlation coefficients, regression coefficients, and intercepts for
      the regression between TEE and RMR and between TEE and BM were highly variable
      between studies. When TEE was adjusted for RMR, there was no significant
      correlation with body fat, and females had a significantly lower TEE than males
      by 1.1 MJ/d (P = 0.005). We conclude that 1) the relationships between TEE and
      RMR and TEE and BM are highly variable between studies with nonzero intercepts,
      precluding use of the traditionally used ratios of TEE to RMR or TEE to BM for
      data comparison; 2) after adjustment of TEE for RMR, TEE is not associated with
      adiposity, and women have a significantly lower TEE than men; and, 3) there are
      insufficient published data to develop prediction models for TEE in adults.

PMID- 7825537
TI  - Selenate fortification improves selenium status of term infants fed soy formula.
AB  - Thirty-three healthy term infants were fed either soy formula (SF, 0.028 mumol
      Se/L; n = 17) or soy formula with added selenate (SF+Se, 0.17 mumol Se/L; n = 16)
      from birth (+4 d) to 16 wk. Selenium intakes of infants fed SF+Se were similar to
      the recommended dietary allowance and significantly greater than those of SF-fed
      infants. The SF group had significantly lower plasma, erythrocyte, and urine
      selenium, and lower plasma and erythrocyte glutathione peroxidase (GPx)
      activities at 16 wk compared to those of infants fed SF+Se. A decrease in plasma
      selenium was observed in SF-fed infants, whereas no differences in plasma
      selenium were found in infants fed SF+Se. These results indicate that selenate
      added to soy formula is highly available and effective at maintaining infant
      plasma and erythrocyte selenium concentrations and GPx activities that are
      greater than those of infants fed soy formula not fortified with selenium.

PMID- 7825538
TI  - Positional distribution of fatty acids in dietary triglycerides: effects on
      fasting blood lipoprotein concentrations in humans.
AB  - We examined the effect of the positional distribution of fatty acids within
      dietary triglycerides on serum lipoproteins. Sixty subjects consumed two diets of
      equal fatty acid composition for 3 wk each. In the palm oil diet 82% of palmitic
      acid was attached to the outer two carbon atoms of glycerol, and 18% to the
      middle carbon. In the diet rich in enzymatically modified palm oil these figures
      were 35% and 65%, respectively. On the modified-fat diet, average lipoprotein
      concentrations showed nonsignificant (P > 0.13) increases of 0.06 mmol/L for
      total, 0.03 mmol/L for HDL, and 0.04 mmol/L for LDL cholesterol compared with
      palm oil. The small increases in total and LDL cholesterol were statistically
      significant in the men (n = 23) but not in the women (n = 37). The ratio of HDL
      to LDL cholesterol and serum triglyceride concentrations were unchanged. Thus, a
      large difference in dietary fatty acid configuration had little effect on
      lipoprotein concentrations in humans.

PMID- 7825539
TI  - Intestinal absorption and lymphatic transport of eicosapentaenoic (EPA),
      docosahexaenoic (DHA), and decanoic acids: dependence on intramolecular
      triacylglycerol structure.
AB  - We compared the absorption of eicosapentaenoic (EPA, 20:5n-3), docosahexaenoic
      (DHA, 22:6n-3), and decanoic acids in mesenteric lymph duct-cannulated rats
      following intragastric administration of two oils with different intramolecular
      triacylglycerol structures. One oil had a specific triacylglycerol structure with
      EPA and DHA located in the sn-2 position and decanoic acid in the sn-1 and sn-3
      positions (specific M-n3-M) whereas the other oil had a random fatty acid
      distribution (random M-n3-M). The mol% (mol/100 mol total fatty acids) of fatty
      acids in the two oils was similar, with approximately 66 mol% of decanoic acid
      and 22 mol% of EPA and DHA. The lymphatic transport (microgram/min) of EPA and
      DHA as well as the mol% in the total lymph lipids were significantly (both P <
      0.01) increased following intragastric administration of specific M-n3-M compared
      with random M-n3-M. The mol% of decanoic acid in the total lymph lipids was
      significantly (P < 0.01) higher after random M-n3-M compared with specific M-n3-M
      but the transport (microgram/min) of decanoic acid was not significantly
      different. We conclude that under our experimental conditions specific M-n3-M
      with EPA and DHA predominantly in the sn-2 position of the triacylglycerols was a
      more readily absorbed source of EPA and DHA and in this context should be
      investigated further for the potential use in clinical nutrition.

PMID- 7825541
TI  - Effect of variable protein intake on whole-body protein turnover in young men and
      women.
AB  - The effect of the amount of protein intake (12% and 21% of total energy intake,
      diet A and diet B, respectively) on nitrogen balance and whole-body protein
      turnover (PT) was measured in 19 young men and 10 young women (aged 30 +/- 5 and
      27 +/- 4 y, respectively). In young adults, mean nitrogen balance was
      approximately zero during diet A whereas it was positive during diet B. In young
      adults, PT was significantly higher during diet B in comparison with diet A. This
      was also seen in elderly subjects, as described before. From a comparison of the
      current data with the data previously obtained in elderly subjects it can be
      concluded that during diet A young adults had PT rates higher than those of
      elderly subjects. During diet B, PT of young men was comparable with the PT of
      elderly men whereas young women still had higher PT rates than elderly women
      (even when corrections were made for differences in body composition).

PMID- 7825540
TI  - Nutritional attributes of traditional flaxseed in healthy young adults.
AB  - The objective was to determine the influence of consuming 50 g flaxseed/d for 4
      wk on several indexes of nutrition in young healthy adults. During flaxseed
      consumption, alpha-linolenate was increased significantly in adipose tissue, and
      n-3 polyunsaturates were increased in plasma lipids. Plasma LDL cholesterol was
      also reduced by up to 8%, and total urinary lignan excretion was increased more
      than fivefold (P < 0.05). Muffins containing 25 g flaxseed did not differ
      significantly from control muffins in their content of thiobarbituric acid
      reactive substances, and alpha-linolenate in the muffins was not significantly
      reduced by baking. Antioxidant vitamins and lipid hydroperoxides in plasma were
      not significantly affected by flaxseed consumption. Bowel movements per week
      increased by 30% while flaxseed was consumed (P < 0.05). We conclude that
      traditional flaxseed has modest beneficial effects on several indexes of
      nutritional status without compromising antioxidant status.

PMID- 7825542
TI  - Influence of the physical form of barley grain on the digestion of its starch in
      the human small intestine and implications for health.
AB  - It has been suggested that incomplete digestion of cereal starch explains the low
      energy values of certain cereals of large particle size. We used human subjects
      with ileostomies to investigate the digestion of barley and to determine whether
      the physical form of barley affects stomal excretion of starch,
      glucooligosaccharides, nitrogen, fat, and calculated energy. Only 2 +/- 1% of
      starch remained undigested after finely milled barley was eaten, but after flaked
      barley was eaten 17 +/- 1% resisted digestion, partly as oligosaccharides (G1
      G10) but largely as intact unpitted starch granules bound by intact cell walls.
      The calculated energy excretion from the stoma was three times higher after
      flaked than after milled barley [51.5 decreasing to 15.3 kJ/g nonstarch
      polysaccharide (NSP, P < 0.001]. NSP, starch, and fat made almost equal
      contributions to the higher energy excretion. It is concluded that possibly the
      botanical source of cereals and certainly processing, other than retrogradation
      of the starch, are important determinants of starch digestibility and energy
      value. Possible clinical implications are introduced.

PMID- 7825543
TI  - Food processing and maize variety affects amounts of starch escaping digestion in
      the small intestine.
AB  - Two meals which differed greatly in resistant starch (RS) concentration, but
      otherwise had similar macronutrient composition (including nonstarch
      polysaccharides), were fed for breakfast to five subjects with ileostomies. The
      high-RS meal included bread made from high-amylose maize, uncooked green banana
      flour, and coarsely ground uncooked wheat. The low-RS meal contained bread made
      from low-amylose maize, cooked green banana flour, and cooked wheat. The effluent
      produced over 14 h was analyzed for the total amount of starch escaping
      digestion. In the low-RS meal 51.8 +/- 6.2 g (mean +/- SD) starch was consumed
      and 2.4 +/- 0.6 g recovered in the effluent, while for the high-RS meal a total
      of 52.7 +/- 8.8 g starch was fed and 19.9 +/- 5.2 g recovered in the effluent.
      The ileostomy results provided additional validation of an in vitro resistant
      starch assay. Scanning electron micrographs of effluent from one subject who
      consumed the high-amylose bread revealed that many intact starch granules escaped
      digestion in the small intestine.

PMID- 7825544
TI  - Iron absorption from the whole diet: comparison of the effect of two different
      distributions of daily calcium intake.
AB  - The possibility of reducing calcium inhibition of iron absorption by decreasing
      calcium intake in lunch and dinner meals, which provided the most dietary iron,
      was examined in 21 healthy female volunteers. During a 10-d period, nonheme iron
      in all meals was extrinsically labeled with radioisotopic iron to a uniform
      specific activity. Iron absorption from two identical 10-d periods was compared
      when meals were labeled with two different iron radioisotopes and when the same
      amount of calcium (937 mg) was distributed in two ways, in either mainly
      breakfast and late evening meals or more evenly in all meals. About 30-50% more
      iron was absorbed when no milk or cheese was served with lunch or dinner. The
      difference was statistically significant. Median iron requirements (1.61 mg/d)
      calculated from body weight and menstrual iron losses agreed with the mean value
      of median iron absorption in the two 10-d periods (1.54 mg/d), which supports the
      validity of the present method. A reasonable separation of calcium and iron
      intakes would improve iron nutrition.

PMID- 7825545
TI  - Injuries produced by judicial hanging. A case report.
AB  - A judicial hanging occurred in the state of Washington. Neck injuries were
      studied by MRI (Magnetic Resonance Imaging) and CT (Computed Tomography). In
      addition, vertebral arteriograms were performed to evaluate the nature of the
      neck injury. This report details the anatomical changes produced by judicial
      hanging.

PMID- 7825546
TI  - Patterns of facial resuscitation injury in infancy.
AB  - Cardiopulmonary resuscitation (CPR)-related artifacts in pediatric rescue that
      have the potential for serious complications in surviving patients have been well
      described in the medical literature. Medically trivial soft-tissue injuries,
      especially of the face and neck, carry predominantly forensic significance and
      have received less attention. We describe such injuries in nine of 25 consecutive
      cases of infants who received CPR, and correlate those injuries with specific
      rescue maneuvers. Techniques for effective investigation and interpretation of
      such injuries are suggested.

PMID- 7825547
TI  - The role of the medical examiner/coroner in organ and tissue procurement for
      transplantation.
AB  - Facts and principles concerning the role of the medical examiner or coroner in
      the procurement of organs or tissue for transplantation are presented. Topics
      discussed are the legalities and the importance of control of the dead body, the
      medical examiner's or coroner's role in the determination of death, recognition
      of and working around procurement artifacts and resultant loss of evidence, the
      medical examiner's or coroner's part in determining suitability of organs for
      transplantation, the medical examiner or coroner's request for donation by the
      family, granting of permission for donation of organs or tissue by the medical
      examiner or coroner, and examination of the mortally injured by the medicolegal
      officer.

PMID- 7825548
TI  - Petechial hemorrhages. A review of pathogenesis.
AB  - Petechial hemorrhages are areas of pericapillary bleeding that occur in a wide
      spectrum of disorders, including some of particular forensic interest. Since
      their potential significance was first recognized by Tardieu in 1855, attention
      has largely focused on their diagnostic importance. There have been only a few
      studies of their mechanism of production. Although the pathogenesis of petechiae
      is often conjectural, it seems that, in spite of their stereotypical gross
      appearance, a variety of pathogenetic mechanisms may be involved. They range from
      mechanical disruption of the capillary wall to subtle cellular injury that
      permits the transit of red blood cells through the endothelial cytoplasm. I
      discuss several conditions that are commonly encountered in forensic practice,
      with emphasis on petechial hemorrhages and their pathogenesis.

PMID- 7825549
TI  - The postmortem incidence of senile ecchymoses.
AB  - Although senile ecchymoses are a well-recognized phenomenon on hospital wards, in
      patients who die in other settings they may be wrongly interpreted as bruising
      caused by physical assault. Therefore, we studied a total of 410 elderly (> 50
      years of age) patients by a prospective examination of autopsy reports to
      elucidate their nature, including their general frequency, their anatomical
      distribution, and their physical appearance. We found a clear association with
      increasing age and a common distribution on the arms, rather than the neck or
      legs. One unique finding is that ecchymoses are related to place of residence, in
      that less mobile elderly persons are more likely to develop this condition,
      possibly as a result of lifting.

PMID- 7825550
TI  - The missing link. An unusual case of embolization.
AB  - Embolization is a well-recognized phenomenon in medicine and forensic pathology
      and generally involves formed blood elements, bone, air, amniotic fluid, or more
      exotic items such as bullets. We report the embolization of a chain-saw link. The
      case demonstrates how, without complete autopsy and investigation, a penetrating
      sharp-force injury could be misdiagnosed and a false conclusion as to the
      commission of a crime could occur. Although the forensic literature is replete
      with examples of bizarre emboli, from bullets to suspected crystals of
      methylmethacrylate, a literature review failed to find a single case of
      penetrating chain-saw-link injury as a cause of traumatic death. Most reports of
      chain-saw incidents cite accidental injuries to hands and arms or dramatic facial
      injuries due to entrapment and recoil (1,2). One fatality occurred from a skull
      fracture and cerebral injury when a 19-year-old man fell onto a saw.

PMID- 7825551
TI  - Suicidal asphyxia by gas mask.
AB  - Antichemical warfare kits that were issued to all Israeli residents 6 months
      before the Gulf War included masks of various types suited to the age of the
      user. During the war, 10 adults died of suffocation due to mishandling of the
      filter of the masks despite the offil Defense Authority's repeated instructions
      to be cautious. These masks remained in the possession of the population after
      the war. We report on six cases of suicidal asphyxia incurred by donning the gas
      mask tightly sealed that have occurred since 1991.

PMID- 7825552
TI  - Suicide by environmental hypoxia (forced depletion of oxygen).
AB  - Suicidal suffocation by forced oxygen depletion (environmental hypoxia) with
      carbon dioxide (CO2) and with propane is discussed in two cases. No toxicologic
      proof was available with the former and circumstantial evidence weighed heavily.
      The latter case demonstrated inhaled propane by an on-scene transthoracic
      aspirate; all other toxicology specimens, including brain, liver, blood, kidney,
      fat, and vitreous, did not contain hydrocarbons. This second fatality was
      complicated by multi-agent overdose, including diphenhydramine, fluoxetine
      (Prozac), and nordiazepam. The designation of these deaths as due to oxygen
      depletion involved careful scrutiny of the autopsy, toxicologic, and scene
      findings. Complete analysis of all factors surrounding these rarely encountered
      suffocation deaths is stressed.

PMID- 7825553
TI  - Postmortem changes in blood amitriptyline concentration.
AB  - Detailed toxicological studies were undertaken on two suicides by amitriptyline
      overdose, one with salicylate also. In the first case, 10 initial blood samples
      taken 21 h after body discovery and an estimated 28 1/2 h after overdose had drug
      concentration (mg/L) ranges of 2.5-12 for amitriptyline (AM), 0.7-3.1 for
      nortriptyline (NOR), and 81-244 for salicylate (SAL). Ten blood samples taken 42
      h later showed corresponding ranges of 1-39 AM, 0.6-7.0 NOR, and 86-310 SAL.
      Sample haemoglobin concentrations (range, 8.7-23.5 g/dl) did not correlate with
      drug concentrations. Postmortem increase in pulmonary vein AM concentration
      occurred more rapidly than in the pulmonary artery, likely reflecting relative
      ease of diffusion across the vessel walls from lung (AM, 60 mg/kg). In nine
      tissue samples, drug concentrations (mg/kg) were highest in the liver: AM, 301;
      and SAL, 670. Considerable drug residue was present in gastric contents, duodenal
      contents, and seven sequential small bowel contents. In both cases, sanguineous
      putrefactive pleural fluid showed higher AM concentrations on the left than on
      the right (2.0 vs 1.4 and 23 vs 16), likely reflecting diffusion from gastric
      drug residue. The detailed case data illustrate the intensity and complexity of
      postmortem drug diffusion from reservoirs in solid organs, such as the lungs, and
      unabsorbed gastric residue, into the blood and putrefactive fluids.

PMID- 7825554
TI  - Postmortem redistribution and degradation of dothiepin. Human case studies and an
      animal model.
AB  - Two suicides took estimated maximum dothiepin doses of 765 and 1875 mg,
      respectively. Initial drug levels in nine and 12 blood samples were 0.26-1.85 and
      4.08-23.98 mg/L, with highest concentrations in the pulmonary veins. Pulmonary
      artery concentrations rose markedly over 18 h: 0.32 rising to 0.9, and 6.54
      rising to 19.53 mg/L. Peripheral blood concentrations were relatively stable.
      Concentrations in liver, heart, lung, and skeletal muscle were, for case 1, 4.3,
      2.92, 18.6, and 1.1 mg/kg; and, for case 2, 52, 16.8, 73.9, and 8.98 mg/kg. New
      Zealand white female rabbits (2.4-3.2 kg) given 20 mg dothiepin hydrochloride
      intravenously were killed with pentobarbital after 1 h. Blood was sampled from
      the thorax, infra-renal inferior vena cava, and supra-renal inferior vena cava at
      0, 1/2, 1, 4, 8, 12, and 24 h postmortem in paired animals. Liver, heart, lung,
      and skeletal muscle were sampled at 0 and 24 h. Mean dothiepin levels in thoracic
      blood rose from 0.43 mg/L at time 0 to 1.73 at 8 h and then fell to 0.61 at 12 h,
      likely reflecting initial redistribution from the lungs (63.4 mg/kg at time 0 and
      27.3 mg/kg at 24 h) followed by putrefaction-associated bacterial degradation.
      Falls in blood drug levels associated with putrefaction were not seen in the
      human cases. Interpretation of postmortem dothiepin blood concentrations is
      complicated by pronounced interindividual variations in in vivo pharmacokinetics,
      the postmortem redistribution phenomenon, and variable drug degradation by
      bacteria.

PMID- 7825555
TI  - Measurements of fentanyl and sufentanil in blood and urine after surgical
      application. Implication in detection of abuse.
AB  - An increase in cases of death from overdose and abuse from fentanyl or sufentanil
      is being encountered by the Bexar County Forensic Science Center in San Antonio,
      Texas. These drugs have been abused almost solely by health care professionals.
      The fentanyl derivatives cannot currently be detected by routine laboratory drug
      screening programs. Forensic toxicology assays that identify the specific analyte
      must be used. We report a sensitive assay for detection of fentanyl and
      sufentanil with a detection limit of -0.5 ng/ml. In addition, results from the
      analysis of urine and blood samples obtained up to 72 h after drug administration
      to five patients undergoing cardiac bypass surgery who had received either
      fentanyl or sufentanil are described. The new procedure enables detection of
      these drugs more readily, in smaller amounts, and for a longer period of time
      after use than previously possible. We hope this will lead to intervention and
      treatment in those abusing the drugs.

PMID- 7825556
TI  - Interpretation of postmortem vaginal acid phosphatase determinations.
AB  - Identification of evidence indicative of sexual assault, including elevated
      levels of acid phosphatase (AP) in the vagina, is an important part of the
      investigation of female homicidal deaths. In this study, vaginal AP levels in 43
      female homicide victims, determined using sodium thymolphthalein as the
      substrate, were retrospectively correlated with semiquantitative assessment of
      spermatozoa in vaginal smears. The results were then compared with those from a
      prospectively studied age-matched group of controls. AP determinations ranged
      from 0 to 6,000 units (U)/L in the homicide group and from 1 to 726 U/L in the
      control group. In both groups, the majority of the AP values (homicide, 65%; and
      controls 85%) were < 100 U/L. Spermatozoa were identified on vaginal smears from
      30% of the homicide victims and 17% of the controls. The spermatozoa-positive
      cases had AP levels that ranged from 2 to 6,000 U/L. In both groups, an AP value
      of > or = 400 U/L was always associated with the presence of spermatozoa on the
      vaginal smear. Intermediate AP values (100-399 U/L) were associated with the
      presence of spermatozoa in 60% of the control group and 22% of the homicide
      group; 18% of the homicide group and 3% of the control group were positive for
      spermatozoa despite AP values of < 100 U/L. In the absence of spermatozoa on a
      vaginal smear, an AP value of > 400 U/L strongly suggests the presence of semen
      that is either oligo- or aspermic. A low or intermediate AP determination,
      however, does not exclude the presence of semen and hence a careful search for
      spermatozoa on the vaginal smear is indicated, regardless of the AP value
      obtained.

PMID- 7825557
TI  - Sudden unexpected death in a male homosexual cohort.
AB  - There has been considerable debate as to the risk of suicide, accidents, and
      homicide in populations at high risk for HIV infection. The purpose of the
      present investigation was to determine the incidence of sudden and unexpected
      deaths in a well-defined cohort of homosexual and bisexual men prospectively
      studied since 1984. All subjects were enrolled in the Pitt Men's Study, the
      Pittsburgh, Pennsylvania, component of the Multicenter AIDS Cohort Study. Of this
      group, 861 were between the ages of 20 and 44, and 35% were seropositive for HIV.
      There were 70 deaths attributed to AIDS. Five additional deaths were classified
      as sudden and unexpected, an annual rate of 0.08% (80/100,000). Only one of these
      was classified by the coroner's office as a suicide; three were due to accidents,
      and one was a drug overdose of undetermined cause. Only two of the five
      unexpected deaths were HIV seropositive, and none had the diagnosis of AIDS. The
      sudden and unexpected death rate in this cohort did not significantly differ from
      the 0.07% (70/100,000) yearly incidence in the age- and race-matched male
      population. Thus, in this well-defined male gay cohort, there does not appear to
      be an increased risk of violent and drug-related deaths in persons at risk for,
      or with a diagnosis of, AIDS.

PMID- 7825558
TI  - Sudden unexpected death in childhood due to unsuspected diabetes mellitus.
AB  - We report the case of an otherwise healthy 11-year-old girl who died suddenly of
      previously undiagnosed diabetes mellitus type I, following a 2-day minor upper
      respiratory infection. Insulin dependent diabetes mellitus (IDDM) is a rare cause
      of sudden death of apparently healthy children. This report demonstrates a
      recommended diagnostic pathway for IDDM from the substantiation of vesicular
      fatty liver to specific pancreatic histological and histochemical changes.

PMID- 7825559
TI  - Coin-rubbing injuries.
AB  - Two cases of injuries caused by "coin rubbing" (Kuasha) are presented. In one
      case these injuries were confined to the neck, raising the possibility of
      strangulation, and in the other to the trunk and limbs, suggesting torture. Coin
      rubbing is practiced by most South-East Asian cultures, which believe that it
      relieves the symptoms of headache, fever, and flu. The causation and
      characteristics of these injuries and their medicolegal importance are discussed.

PMID- 7825560
TI  - Endotoxemia in sudden infant death syndrome.
AB  - Endotoxemia has been proposed as a significant cause of Sudden Infant Death
      Syndrome (SIDS). We examined postmortem sera from left and right heart samples of
      21 SIDS cases (1989 definition) and 23 controls. The controls were < 1 year of
      age and had died suddenly and unexpectedly of infection, abuse, suffocation,
      blunt injury, or fire and smoke inhalation. Endotoxin was measured without
      knowledge of the clinical status by using a kinetic modification of the
      chromogenic limulus amoebocyte lysate assay. The SIDS cases had insignificant
      concentrations of endotoxin in serum, whereas some of the controls who
      experienced blunt injury, abuse, or severe infection exhibited moderately
      elevated concentrations. Postmortem interval and postmortem blood culture results
      did not materially affect endotoxin concentrations. Thus, we conclude that
      endotoxemia is not a substantial pathophysiologic event in SIDS.

PMID- 7825561
TI  - Restraint asphyxiation.

PMID- 7825562
TI  - Oleo capsicum (O.C.): the need for careful evaluation.

PMID- 7825563
TI  - 1994 ASHG presidential address. Who are we? Where are we going? Anticipating the
      21st century.

PMID- 7825564
TI  - Quantitative comparison of FMR1 gene expression in normal and premutation
      alleles.
AB  - We report studies on FMR1 gene expression in cells derived from male premutation
      carriers. Transcription of FMR1 genes with CGG-repeat lengths within the
      premutation range was demonstrated to be normal. Repeat lengths are faithfully
      transcribed into FMR1 mRNAs, which have steady-state levels, as measured by RNase
      protection, similar to those of normal cells. Premutation transcripts also are
      shown to have normal turnover, with the FMR1 mRNA half-life estimated to be 12 h.
      Measurement of FMR1 protein was also found to be in similar abundance in normal
      and premutation cell lines. These data support the nonpenetrant status of
      premutation carriers of fragile X syndrome and suggest that the occasional case
      reports to the contrary may reflect either other causes, including low-level
      mosaicism for larger, methylated FMR1 alleles, or simply coincidence.

PMID- 7825565
TI  - Linkage disequilibrium as a gene-mapping tool.

PMID- 7825566
TI  - Somatic heterogeneity of the CTG repeat in myotonic dystrophy is age and size
      dependent.
AB  - The most common form of adult muscular dystrophy, myotonic dystrophy (DM), is
      caused by the abnormal expansion of the CTG repeat, located in the 3' UTR of the
      DM gene. The expanded-CTG allele often presents as a diffused band on Southern
      blot analysis, suggesting somatic mosaicism. In order to study the somatic
      instability of the CTG repeat, we have investigated the dynamics of the size
      heterogeneity of the CTG expansion. Size heterogeneity is shown as a smear on
      Southern blot and is measured by the midpeak-width ratio of the expanded allele
      to the normal sized allele. The ratio is also corrected for compression in the
      higher-molecular-weight region. It is found that the size heterogeneity of the
      expanded-CTG repeats, of 173 DM patients, correlates well with the age of the
      patient (r = .81, P << .001). The older patients show larger size variation. This
      correlation is independent of the sex of either the patient or the transmitting
      parent. The size heterogeneity of the expansion, based on age groups, is also
      dependent on the size of the expanded trinucleotide repeat. However, obvious size
      heterogeneity is not observed in congenital cases, regardless of the size of
      expansion. Comparison of individual patient samples collected at two different
      times has confirmed that the degree of size heterogeneity increases with age and
      has revealed a subtle but definite upward shift in the size of the expanded-CTG
      allele. The progression of the CTG repeat toward larger expansion with age is
      further confirmed by small-pool PCR assay that resolved the heterogeneous
      fragments into discrete bands.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7825567
TI  - Normal variation at the myotonic dystrophy locus in global human populations.
AB  - Myotonic dystrophy (DM) is a dominant neuromuscular disease that results from an
      unstable CTG-repeat expansion in the 3' UTR of the myotonin kinase gene at
      19q13.3. This repeat is normally polymorphic with a trimodal distribution
      reflecting 5-, 11-17-, and 19-30-repeat-length alleles. An absolute association
      between expanded CTG alleles and the 1-kb insertion allele of an intragenic
      polymorphism in Caucasians has led to the proposal that the 5-repeat allele gives
      rise to alleles of 19-30 repeats, from which expanded alleles are derived, a
      transition not involving the 11-17-repeat alleles. A survey of eight global
      populations confirms the stability of the 11-17-repeat alleles but shows
      disociation between the 1-kb insertion polymorphism and both the 5- and 19-30
      repeat-length alleles. These data indicate more than one ancestral allele from
      which expanded alleles are derived and suggest that widely variable population
      frequencies of DM may reflect distinct frequencies of such predisposed alleles.

PMID- 7825568
TI  - Functional expression of human mutant phosphofructokinase in yeast: genetic
      defects in French Canadian and Swiss patients with phosphofructokinase
      deficiency.
AB  - Human phosphofructokinase (PFK) is a tetrameric enzyme, encoded by muscle, liver,
      and platelet genes. Deficiency of muscle PFK (PFK-M), glycogenosis type VII
      (Tarui disease), is an autosomal recessive disorder characterized by an
      exertional myopathy and hemolytic syndrome. Several disease-causing mutations
      have been identified in the PFK-M gene in Japanese, Ashkenazi Jewish, and Italian
      patients. We describe the genetic defects in French Canadian and Swiss patients
      with the disease, and we use a genetically well-defined yeast system devoid of
      endogenous PFK for structure-function studies of the mutant PFKs. A G-to-A
      transition at codon 209-in exon 8 of the PFK-M gene, changing an encoded Gly to
      Asp, is responsible for the disease in a homozygous French Canadian patient. Gly
      209-mutated protein is completely inactive in the yeast system. The Swiss patient
      is a genetic compound, carrying a G-to-A transition at codon 100 in exon 6 (Arg
      to Gln) and a G-to-A transition at codon 696 in exon 22 (Arg to His). The mutants
      expressed in yeast generate functional enzyme with modest changes in thermal
      stability. The advantages and limitations of the yeast system for expression of
      human mutant PFKs are discussed.

PMID- 7825570
TI  - 'Twixt cup and lip: how intractable is the ascertainment problem?

PMID- 7825569
TI  - Thermolabile 5,10-methylenetetrahydrofolate reductase as a cause of mild
      hyperhomocysteinemia.
AB  - Thermolability of 5,10-methylenetetrahydrofolate reductase (MTHFR) was examined
      as a possible cause of mild hyperhomocysteinemia in patients with premature
      vascular disease. Control subjects and vascular patients with mild
      hyperhomocysteinemia and with normohomocysteinemia were studied. The mean (+/-
      SD) specific MTHFR activity in lymphocytes of 22 control subjects was 15.6 (+/-
      4.7) nmol CH2O/mg protein/h (range: 9.1-26.6), and the residual activity (+/- SD)
      after heat inactivation for 5 min at 46 degrees C was 55.3 (+/- 12.0)% (range:
      35.9-78.3). By measurement of MTHFR activity, two distinct subgroups of
      hyperhomocysteinemic patients became evident. One group (n = 11) had thermolabile
      MTHFR with a mean (+/- SD) specific activity of 8.7 (+/- 2.1) nmol CH2O/mg
      protein/h (range: 5.5-12.7) and a residual activity, after heat inactivation,
      ranging from 0% to 33%. The other group (n = 28) had normal specific activity (+/
      SD) of 21.5 (+/- 7.2) nmol CH2O/mg protein/h (range: 10.0-39.0) and a normal
      residual activity (+/- SD) of 53.8 (+/- 9.2)% (range: 33.1-71.5) after heat
      inactivation. The mean (+/- SD) specific activity of 29 normohomocysteinemic
      patients was 20.7 (+/- 6.5) nmol CH2O/mg protein/h (range: 9.4-33.8), and the
      mean (+/- SD) residual activity after heat inactivation was 58.2 (+/- 10.2)%
      (range: 43.0-82.0). Thus, in 28% of the hyperhomocysteinemic patients with
      premature vascular disease, abnormal homocysteine metabolism could be attributed
      to thermolabile MTHFR.

PMID- 7825571
TI  - Transcription of the dystrophin gene in normal tissues and in skeletal muscle of
      a family with X-linked dilated cardiomyopathy.
AB  - We recently described a family where a deletion of the dystrophin gene was
      associated with a severe dilated cardiomyopathy without skeletal muscle weakness.
      The deletion removed the muscle promoter region and the first muscle exon, but
      not the brain or Purkinje-cell promoters. Dystrophin was detected
      immunocytochemically in the skeletal muscle from this family, despite the fact
      that the deletion eliminated the transcriptional start site of the muscle
      isoform. In order to determine which promoter was driving dystrophin
      transcription in skeletal muscle of these individuals, we first evaluated the
      expression of the exon 1 of muscle, brain, and Purkinje-cell isoforms in normal
      human skeletal and cardiac muscles and in mouse brain and cerebellum. Our data
      indicate that, with the exception of minimal expression of the brain isoform,
      only the muscle isoform is significantly transcribed in skeletal muscle, whereas
      both the exon 1 muscle and brain isoforms are highly expressed in cardiac muscle.
      In contrast to what is observed in normal muscle, the skeletal muscle of our
      patients showed expression of both the brain and the Purkinje-cell isoforms. The
      overexpression, in skeletal muscle, of these two isoforms thus appears to be of
      crucial importance in preventing a myopathy in these affected males. The reason
      for the severe cardiomyopathy remains speculative, in the absence of dystrophin
      data on their heart. However, we have found in the 5' end of intron 1, a region
      deleted in our cases, regulatory sequences that might be of importance for
      dystrophin expression in various tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7825572
TI  - Frameshift deletions of exons 3-7 and revertant fibers in Duchenne muscular
      dystrophy: mechanisms of dystrophin production.
AB  - Duchenne muscular dystrophy (DMD) patients with mutations that disrupt the
      translational reading frame produce little or no dystrophin. Two exceptions are
      the deletion of exons 3-7 and the occurrence of rare dystrophin-positive fibers
      (revertant fibers) in muscle of DMD patients. Antibodies directed against the
      amino-terminus and the 5' end of exon 8 did not detect dystrophin in muscle from
      patients who have a deletion of exons 3-7. However, in all cases, dystrophin was
      detected with an antibody directed against the 3' end of exon 8. The most likely
      method of dystrophin production in these cases is initiation at a new start codon
      in exon 8. We also studied two patients who have revertant fibers: one had an
      inherited duplication of exons 5-7, which, on immunostaining, showed two types of
      revertant fibers; and the second patient had a 2-bp nonsense mutation in exon 51,
      which creates a cryptic splice site. An in-frame mRNA that uses this splice site
      in exon 51 was detected. Immunostaining demonstrated the presence of the 3' end
      of exon 51, which is in agreement with the use of this mRNA in revertant fibers.
      The most likely method of dystrophin production in these fibers is a second
      mutation that restores the reading frame.

PMID- 7825573
TI  - Molecular and cellular analysis of the DNA repair defect in a patient in
      xeroderma pigmentosum complementation group D who has the clinical features of
      xeroderma pigmentosum and Cockayne syndrome.
AB  - Xeroderma pigmentosum (XP) and Cockayne syndrome (CS) are quite distinct genetic
      disorders that are associated with defects in excision repair of UV-induced DNA
      damage. A few patients have been described previously with the clinical features
      of both disorders. In this paper we describe an individual in this category who
      has unusual cellular responses to UV light. We show that his cultured fibroblasts
      and lymphocytes are extremely sensitive to irradiation with UV-C, despite a level
      of nucleotide excision repair that is 30%-40% that of normal cells. The
      deficiency is assigned to the XP-D complementation group, and we have identified
      two causative mutations in the XPD gene: a gly-->arg change at amino acid 675 in
      the allele inherited from the patient's mother and a -1 frameshift at amino acid
      669 in the allele inherited from his father. These mutations are in the C
      terminal 20% of the 760-amino-acid XPD protein, in a region where we have
      recently identified several mutations in patients with trichothiodystrophy.

PMID- 7825574
TI  - The human homologue of the Drosophila melanogaster flightless-I gene (flil) maps
      within the Smith-Magenis microdeletion critical region in 17p11.2.
AB  - The Smith-Magenis syndrome (SMS) appears to be a contiguous-gene-deletion
      syndrome associated with a proximal deletion of the short arm of chromosome 17 in
      band p11.2. The spectrum of clinical findings includes short stature,
      brachydactyly, developmental delay, dysmorphic features, sleep disturbances, and
      behavioral problems. The complex phenotypic features suggest deletion of several
      contiguous genes. However, to date, no protein-encoding gene has been mapped to
      the SMS critical region. Recently, the Drosophila melanogaster flightless-I gene,
      fliI, and the homologous human cDNA have been isolated. Mutations in fliI result
      in loss of flight ability and, when severe, cause lethality due to incomplete
      cellularization with subsequent abnormal gastrulation. Here, we demonstrate that
      the human homologue (FLI) maps within the SMS critical region. Genomic cosmids
      were used as probes for FISH, which localized this gene to the 17p11.2 region.
      Somatic-cell hybrid-panel mapping further localized this gene to the SMS critical
      region. Southern blot analysis of somatic-cell hybrids and/or FISH analysis of
      lymphoblastoid cell lines from 12 SMS patients demonstrates the deletion of one
      copy of FLI in all SMS patients analyzed.

PMID- 7825575
TI  - Likelihood methods for locating disease genes in nonequilibrium populations.
AB  - Until recently, attempts to map disease genes on the basis of population
      associations with linked markers have been based on expected values of linkage
      disequilibrium. These methods suffer from the large variances imposed on
      disequilibrium measures by the evolutionary process, but a more serious problem
      for many diseases is that they assume an equilibrium population. For diseases
      that arose only a few hundred generations ago, it is more appropriate to
      concentrate on the initial growth phase of the disease. We invoke a Poisson
      branching process for this early growth, and estimate the likelihood for the
      recombination fraction between marker and disease loci, on the basis of simulated
      disease populations. The limits of the resulting support intervals for the
      recombination fraction vary inversely with the age of the disease in generations.
      We illustrate the procedure with data on cystic fibrosis and diastrophic
      dysplasia, for which the method appears appropriate, and for Friedreich ataxia
      and Huntington disease, for which it does not. A valuable aspect of the method is
      the ability in some cases to compare likelihoods of the three orders for a
      disease locus and two linked marker loci.

PMID- 7825576
TI  - Autosomal dominant familial spastic paraplegia: reduction of the FSP1 candidate
      region on chromosome 14q to 7 cM and locus heterogeneity.
AB  - Three large pedigrees of German descent with autosomal dominant "pure" familial
      spastic paraplegia (FSP) were characterized clinically and genetically. Haplotype
      and linkage analyses, with microsatellites covering the FSP region on chromosome
      14q (locus FSP1), were performed. In pedigree W, we found a haplotype that
      cosegregates with the disease and observed three crossing-over events, reducing
      the FSP1 candidate region to 7 cM; in addition, the observation of apparent
      anticipation in this family suggests a trinucleotide repeat expansion as the
      mutation. In pedigrees D and S, the gene locus could be excluded from the whole
      FSP1 region, confirming the locus heterogeneity of autosomal dominant FSP.

PMID- 7825577
TI  - Autosomal dominant familial spastic paraplegia: tight linkage to chromosome 15q.
AB  - Autosomal dominant, uncomplicated familial spastic paraplegia (FSP) is a
      genetically heterogeneous disorder characterized by insidiously progressive lower
      extremity spasticity. Recently, a locus on chromosome 14q was shown to be tightly
      linked with the disorder in one of three families. We performed linkage analysis
      in a kindred with autosomal dominant uncomplicated FSP. After excluding the
      chromosome 14q locus, we observed tight linkage of the disorder to a group of
      markers on chromosome 15q (maximum two-point lod score 9.70; theta = .05). Our
      results clearly establish the existence of a locus for autosomal dominant FSP in
      the centromeric region of chromosome 15q. Comparing clinical and genetic features
      in FSP families linked to chromosome 14q with those linked to chromosome 15q may
      provide insight into the pathophysiology of this disorder.

PMID- 7825578
TI  - The gene for spinal cerebellar ataxia 3 (SCA3) is located in a region of
      approximately 3 cM on chromosome 14q24.3-q32.2.
AB  - SCA3, the gene for spinal cerebellar ataxia 3, was recently mapped to a 15-cM
      interval between D14S67 and D14S81 on chromosome 14q, by linkage analysis in two
      families of French ancestry. The SCA3 candidate region has now been refined by
      linkage analysis with four new microsatellite markers (D14S256, D14S291, D14S280,
      and AFM343vf1) in the same two families, in which 19 additional individuals were
      genotyped, and in a third French family. Combined two-point linkage analyses show
      that the new markers, D14S280 and AFM343vf1, are tightly linked to the SCA3
      locus, with maximal lod scores, at recombination fraction, (theta) = .00, of 7.05
      and 13.70, respectively. Combined multipoint and recombinant haplotype analyses
      localize the SCA3 locus to a 3-cM interval flanked by D14S291 and D14S81. The
      same allele for D14S280 segregates with the disease locus in the three kindreds.
      This allele is frequent in the French population, however, and linkage
      disequilibrium is not clearly established. The SCA3 locus remains within the 29
      cM region on 14q24.3-q32.2 containing the gene for the Machado-Joseph disease,
      which is clinically related to the phenotype determined by SCA3, but it cannot
      yet be concluded that both diseases result from alterations of the same gene.

PMID- 7825579
TI  - Refinement of the spinal muscular atrophy locus by genetic and physical mapping.
AB  - We report the mapping and characterization of 12 microsatellite markers including
      11 novel markers. All markers were generated from overlapping YAC clones that
      span the spinal muscular atrophy (SMA) locus. PCR amplification of 32 overlapping
      YAC clones shows that 9 of the new markers (those set in italics) map to the
      interval between the two previous closest flanking markers (D5S629 and D5S557):
      cen-D5S6-D5S125-D5S435-D5S1407- D5S629-D5S1410-D5S1411/D5S1412-D5S1413- D5S1414
      D5Z8-D5Z9-CATT1-D5Z10/D5Z6- D5S557-D5S1408-D5S1409-D5S637-D5S351-MA P1B-tel. Four
      of these new markers detect multiple loci in and out of the SMA gene region.
      Genetic analysis of recombinant SMA families indicates that D5S1413 is a new
      proximal flanking locus for the SMA gene. Interestingly, among the 40 physically
      mapped loci, the 14 multilocus markers map contiguously to a genomic region that
      overlaps, and perhaps helps define, the minimum genetic region encompassing the
      SMA gene(s).

PMID- 7825580
TI  - Linkage disequilibrium and haplotype analysis among Polish families with spinal
      muscular atrophy.
AB  - Spinal Muscular Atrophy (SMA) is an inherited degenerative disorder of anterior
      horn cells that results in progressive muscle weakness and atrophy. The autosomal
      recessive forms of childhood-onset SMA have been mapped to chromosome 5q11.2
      13.3, in a number of studies examining different populations. A total of 9 simple
      sequence repeat markers were genotyped against 32 Polish families with SMA. The
      markers span an approximately 0.7 cM region defined by the SMA flanking markers
      D5S435 and MAP1B. Significant linkage disequilibrium (corrected P < .05) was
      detected at four of these markers, with D/Dmax values of < or = .89. Extended
      haplotype analysis revealed a predominant haplotype associated with SMA. The
      apparently high mutation rate of some of the markers has resulted in a number of
      haplotypes that vary slightly from this predominant haplotype. The predominant
      haplotype and these closely related patterns represent 25% of the disease
      chromosomes and none of the nontransmitted parental chromosomes. This predominant
      haplotype is present both in patients with acute (type I) and in chronic (types
      II and III) forms of SMA and occurs twice in a homozygous state, both times in
      children with chronic SMA.

PMID- 7825581
TI  - Gene mapping of Usher syndrome type IIa: localization of the gene to a 2.1-cM
      segment on chromosome 1q41.
AB  - Usher syndrome type II is associated with hearing loss and retinitis pigmentosa
      but not with any vestibular problems. It is known to be genetically
      heterogeneous, and one locus (termed USH2A) has been linked to chromosome 1q41.
      In an effort to refine the localization of USH2A, the genetic map of the region
      between and adjacent to the marker loci previously recognized as flanking USH2A
      (D1S70 and PPOL) is updated. Analysis of marker data on 68 Usher II families
      places the USH2A gene into a 2.1-cM region between the markers D1S237 and D1S229.
      The gene for transforming growth factor beta 2 (TGFB2) and the gene for the
      homeodomain box (HLX1) are both eliminated as candidates for USH2A, by virtue of
      their localization outside these flanking markers. The earlier finding of genetic
      heterogeneity was confirmed in six new families, and the proportion of unlinked
      Usher II families is estimated at 12.5%. The placement of the USH2A gene into
      this region will aid in the physical mapping and isolation of the gene itself.

PMID- 7825582
TI  - X-linked progressive mixed deafness: a new microdeletion that involves a more
      proximal region in Xq21.
AB  - We report a large two-generation pedigree with seven affected males segregating
      for an X-linked mixed conductive sensorineural deafness. The patients present
      with atypical Mondini-like dysplasia, dilated petrous facial canal, dilatation of
      the internal auditory meatus fully connected with enlarged cochlear canals, and,
      in one patient, a wide bulbous posterior labyrinth. Obligatory carrier females
      are mildly affected. Molecular characterization of this family revealed a
      deletion of locus DXS169, in Xq21.1. Loci DXS72 and DXS26, which, respectively,
      flank DXS169 proximally and distally, were intact. Since a gene responsible for X
      linked progressive mixed deafness with perilymphatic gusher (DFN3) has previously
      been assigned by deletion mapping to a slightly more distal interval between
      DXS26 and DXS121, this study indicates either two different deafness genes or the
      involvement of a very large region in Xq21.

PMID- 7825583
TI  - Mapping of the gene for Machado-Joseph disease within a 3.6-cM interval flanked
      by D14S291/D14S280 and D14S81, on the basis of studies of linkage and linkage
      disequilibrium in 24 Japanese families.
AB  - The gene locus of Machado-Joseph disease (MJD) has recently been mapped within a
      29-cM subregion of 14q chromosome. We did a linkage study of 24 multigenerational
      MJD Japanese pedigrees, in an attempt to narrow the candidate region of this
      gene. Pairwise and multipoint linkage analysis, together with haplotype
      segregation analysis, led to the conclusion that the MJD gene is located at the
      6.8-cM interval between D14S256 and D14S81 (Zmax = 24.78, multipoint linkage
      analysis). D14S291 and D14S280, located at the center of this interval, showed no
      obligate recombination with the MJD gene (Zmax = 5.93 for D14S291 and 9.99 for
      D14S280). A weak, but significant, linkage disequilibrium of MJD gene was noted
      with D14S81 (P < .05) but not with D14S291 or D14S280. These results suggest that
      a 3.6-cM interval flanked by D14S291/D14S280 and D14S81 is the most likely
      location of the MJD gene and that it is closest to D14S81.

PMID- 7825584
TI  - Linkage analysis of the nail-patella syndrome.
AB  - Nail-patella syndrome (NPS) is an autosomal dominant disorder characterized by
      dysplasia of nails and patella, decreased mobility of the elbow, iliac horns,
      and, in some cases, nephropathy. The disorder has been mapped to the long arm of
      chromosome 9, but the precise localization and identity of the NPS gene are
      unknown. Linkage analysis in three NPS families, using highly informative
      dinucleotide repeat polymorphisms on 9q33-q34, confirmed linkage of NPS to this
      chromosome. Recombinations were detected, by two-point linkage analysis, between
      NPS and the centromeric markers D9S60 and the gelsolin gene and the telomeric
      markers D9S64 and D9S66, in one of the families. Haplotype analysis suggested an
      additional recombination between NPS and the argininosuccinate synthetase (ASS)
      gene. These results localize the NPS gene to an interval on 9q34.1, distal to
      D9S60 and proximal to ASS, comprising a genetic distance of approximately 9 cM.
      This represents a significant refinement in the localization of the NPS gene.

PMID- 7825585
TI  - Refining the localization of the PKD2 locus on chromosome 4q by linkage analysis
      in Spanish families with autosomal dominant polycystic kidney disease type 2.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is a genetically
      heterogeneous disorder. At least two distinct forms of ADPKD are now well
      defined. In approximately 86% of affected European families, a gene defect
      localized to 16p13.3 was responsible for ADPKD, while a second locus has been
      recently localized to 4q13-q23 as candidate for the disease in the remaining
      families. We present confirmation of linkage to microsatellite markers on
      chromosome 4q in eight Spanish families with ADPKD, in which the disease was not
      linked to 16p13.3. By linkage analysis with marker D4S423, a maximum lod score of
      9.03 at a recombination fraction of .00 was obtained. Multipoint linkage
      analysis, as well as a study of recombinant haplotypes, placed the PKD2 locus
      between D4S1542 and D4S1563, thereby defining a genetic interval of approximately
      1 cM. The refined map will serve as a genetic framework for additional genetic
      and physical mapping of the region and will improve the accuracy of
      presymptomatic diagnosis of PKD2.

PMID- 7825586
TI  - An evaluation of genetic heterogeneity in 145 breast-ovarian cancer families.
      Breast Cancer Linkage Consortium.
AB  - The breast-ovary cancer-family syndrome is a dominant predisposition to cancer of
      the breast and ovaries which has been mapped to chromosome region 17q12-q21. The
      majority, but not all, of breast-ovary cancer families show linkage to this
      susceptibility locus, designated BRCA1. We report here the results of a linkage
      analysis of 145 families with both breast and ovarian cancer. These families
      contain either a total of three or more cases of early-onset (before age 60
      years) breast cancer or ovarian cancer. All families contained at least one case
      of ovarian cancer. Overall, an estimated 76% of the 145 families are linked to
      the BRCA1 locus. None of the 13 families with cases of male breast cancer appear
      to be linked, but it is estimated that 92% (95% confidence interval 76%-100%) of
      families with no male breast cancer and with two or more ovarian cancers are
      linked to BRCA1. These data suggest that the breast-ovarian cancer-family
      syndrome is genetically heterogeneous. However, the large majority of families
      with early-onset breast cancer and with two or more cases of ovarian cancer are
      likely to be due to BRCA1 mutations.

PMID- 7825587
TI  - Breast and ovarian cancer incidence in BRCA1-mutation carriers. Breast Cancer
      Linkage Consortium.
AB  - Dominant predisposition to early-onset breast cancer and/or ovarian cancer in
      many families is known to be the result of germ-line mutations in a gene on
      chromosome 17q, known as BRCA1. In this paper we use data from families with
      evidence of linkage to BRCA1 to estimate the age-specific risks of breast and
      ovarian cancer in BRCA1-mutation carriers and to examine the variation in risk
      between and within families. Under the assumption of no heterogeneity of risk
      between families, BRCA1 is estimated to confer a breast cancer risk of 54% by age
      60 years (95% confidence interval [CI] 27%-71%) and an ovarian cancer risk of 30%
      by age 60 years (95% CI 8%-47%). Similar lifetime-risk estimates are obtained by
      examining the risks of contralateral breast cancer and of ovarian cancer, in
      breast cancer cases in linked families. However, there is significant evidence of
      heterogeneity of risk between families; a much better fit to the data is obtained
      by assuming two BRCA1 alleles, one conferring a breast cancer risk of 62% and an
      ovarian cancer risk of 11% by age 60 years, the other conferring a breast cancer
      risk of 39% and an ovarian cancer risk of 42%, with the first allele representing
      71% of all mutations (95% CI 55%-87%). There is no evidence of clustering of
      breast and ovarian cancer cases within families.

PMID- 7825588
TI  - Recurrence of the R408W mutation in the phenylalanine hydroxylase locus in
      Europeans.
AB  - The relative frequency of the common phenylalanine hydroxylase (PAH) mutation
      R408W and its associations with polymorphic RFLP, VNTR, and short-tandem-repeat
      (STR) sites in the PAH gene were examined in many European populations and one
      representative North American population of defined European descent. This
      mutation was found to cluster in two regions: in northwest Europe among Irish and
      Scottish peoples, and in eastern Europe, including the Commonwealth of
      Independent States. This allele was significantly less frequent in intervening
      populations. In eastern European populations, the R408W mutation is strongly
      associated with RFLP haplotype 2, the three-copy VNTR allele (VNTR 3), and the
      240-bp STR allele. In northwestern European populations, it is strongly
      associated with RFLP haplotype 1, the VNTR allele containing eight repeats (VNTR
      8), and the 244-bp STR allele. An examination of the linkage between the R408W
      mutation and highly polymorphic RFLP, VNTR, and STR haplotypes suggests that
      recurrence is the most likely mechanism to account for the two different major
      haplotype associations of R408W in Europe.

PMID- 7825590
TI  - Multiple glucose 6-phosphate dehydrogenase-deficient variants correlate with
      malaria endemicity in the Vanuatu archipelago (southwestern Pacific).
AB  - In studying the relationship between genetic abnormalities of red blood cells and
      malaria endemicity in the Vanuatu archipelago in the southwestern Pacific, we
      have found that of 1,442 males tested, 98 (6.8%) were G6PD deficient. The
      prevalence of GdPD deficiency varied widely (0%-39%), both from one island to
      another and in different parts of the same island, and generally correlated
      positively with the degree of malaria transmission. The properties of G6PD from
      GdPD-deficient subjects were analyzed in a subset of 53 samples. In all cases the
      residual red-blood-cell activity was < 10%. There were three phenotypic patterns.
      PCR amplification and sequencing of the entire coding region of the G6PD gene
      showed that the first of these patterns corresponded to G6PD Union (nucleotide
      1360C-->T; amino acid 454Arg-->Cys), previously encountered elsewhere. Analysis
      of samples exhibiting the second pattern revealed two new mutants: G6PD Vanua
      Lava (nucleotide 383T-->C; amino acid 128Leu-->Pro) and G6PD Namoru (nucleotide
      208T-->C; amino acid 70Tyr-->His); in three samples, the underlying mutation has
      not yet been identified. Analysis of the sample exhibiting the third pattern
      revealed another new mutant: G6PD Naone (nucleotide 497G-->A; amino acid 166Arg-
      >His). Of the four mutations, G6PD Union and G6PD Vanua Lava have a polymorphic
      frequency in more than one island; and G6PD Vanua Lava has also been detected in
      a sample from Papua New Guinea. G6PD deficiency is of clinical importance in
      Vanuatu because it is a cause of neonatal jaundice and is responsible for
      numerous episodes of drug-induced acute hemolytic anemia.

PMID- 7825589
TI  - Genetic variation in lipoprotein (a) levels in families enriched for coronary
      artery disease is determined almost entirely by the apolipoprotein (a) gene
      locus.
AB  - Lipoprotein (a) (Lp[a]) is a cholesterol-rich lipoprotein resembling LDL but also
      containing a large polypeptide designated apolipoprotein (a) (apo[a]). Its levels
      are highly variable among individuals and, in a number of studies, are strongly
      correlated with the risk of coronary artery disease (CAD). In an effort to
      determine which genes control Lp(a) levels, we have studied 25 multiplex families
      (comprising 298 members) enriched for CAD. The apo(a) gene was genotyped among
      the families, using a highly informative pulse-field gel electrophoresis
      procedure. In addition, polymorphisms of the gene for the other major protein of
      Lp(a), apolipoprotein B (apoB), were examined. Quantitative sib-pair linkage
      analysis indicates that apo(a) is the major gene controlling Lp(a) levels in this
      CAD population (P = .001; 99 sib pairs), whereas the apoB gene demonstrated no
      significant quantitative linkage effect. We estimate that the apo(a) locus
      accounts for < or = 98% of variance of Lp(a) serum levels. Approximately 43% of
      this variation is explained by size polymorphisms within the apo(a) gene. These
      results indicate that the apo(a) gene is the major determinant of Lp(a) serum
      levels not only in the general population but also in a high-risk CAD population.

PMID- 7825591
TI  - A familial "balanced" 3;9 translocation with cryptic 8q insertion leading to
      deletion and duplication of 9p23 loci in siblings.
AB  - A child with phenotypic features of the 9p- syndrome, including metopic
      craniosynostosis, small ears, abdominal wall defect, and mental retardation, as
      well as hypopigmentation, was found to have a cytogenetically balanced 3;9
      translocation, with breakpoints at 3p11 and 9p23, inherited from his
      phenotypically normal father. Molecular analysis showed heterozygous deletion of
      the TYRP (tyrosinase-related protein) locus, as well as loci D9S157, D9S274,
      D9S268, and D9S267, in the child but in neither parent. FISH analysis of the
      proband's father indicated that loci deleted in his son, including TYRP, were
      present on neither the der(3) nor the der(9) translocation products but had been
      inserted into the long arm of chromosome 8. Therefore, the apparent deletion of
      these loci in the proband was the result of meiotic segregation of the father's
      3;9 translocation chromosomes together with his normal chromosome 8 (not bearing
      the insertion from 9p23). Neither the deletion of these 9p23 loci from the
      translocation chromosomes nor their insertion into 8q was detectable by standard
      chromosome banding techniques. The proband's sister exhibited speech delay, mild
      facial dysmorphism, and renal malformation, and her karyotype was 46,XX.
      Molecular analysis showed that she had inherited normal chromosomes 3 and 9, as
      well as the chromosome 8 with the insertion of 9p23 material, from her
      father.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7825592
TI  - Microsatellite-based fine mapping of the Van der Woude syndrome locus to an
      interval of 4.1 cM between D1S245 and D1S414.
AB  - Van der Woude syndrome (VWS) is an autosomal dominant craniofacial disorder
      characterized by lip pits, clefting of the primary or secondary palate, and
      hypodontia. The gene has been localized, by RFLP-based linkage studies, to region
      1q32-41 between D1S65-REN and D1S65-TGFB2. In this study we report the linkage
      analysis of 15 VWS families, using 18 microsatellite markers. Multipoint linkage
      analysis places the gene, with significant odds of 2,344:1, in a 4.1-cM interval
      flanked by D1S245 and D1S414. Two-point linkage analysis demonstrates close
      linkage of VWS with D1S205 (lod score [Z] = 24.41 at theta = .00) and with D1S491
      (Z = 21.23 at theta = .00). The results revise the previous assignment of the VWS
      locus and show in an integrated map of the region 1q32-42 that the VWS gene
      resides more distally than previously suggested. When information about
      heterozygosity of the closely linked marker D1S491 in the affected members of the
      VWS family with a microdeletion is taken into account, the VWS critical region
      can be further narrowed, to the 3.6-cM interval between D1S491 and D1S414.

PMID- 7825593
TI  - Inferring a major gene for quantitative traits by using segregation analysis with
      tests on transmission probabilities: how often do we miss?
AB  - In an effort to safeguard against false inference of a major gene in segregation
      analysis, it has become common practice to require nonrejection of the Mendelian
      transmission hypothesis (Mendelian tau's) and rejection of the no-transmission
      hypothesis (equal tau's). However, it is not known how often one would actually
      infer a major gene, when one exists, by using these criteria. A simulation study
      was undertaken to investigate this issue. Segregation of a Mendelian gene under a
      variety of models was simulated in families with both parents and three children.
      The data were analyzed by using POINTER; the assumptions under the generating and
      analysis models were identical. By design, the power to reject the no-major
      effect hypothesis (q = 0) was > 60% for all models considered; tests on the
      transmission probabilities were carried out only when q = 0 was rejected, using
      alpha = 0.05 for all tests. The rates of Mendelian inference were mostly in the
      range of 22%-50% under recessive inheritance, versus 60%-99% under dominant
      inheritance. Notably, it was not possible to resolve the transmission (from among
      Mendelian tau's, equal tau's, and general unconstrained tau's) in approximately
      20%-70% of the cases under recessive models, versus 3%-15% under dominant models.
      Therefore, while tests on transmission probabilities can serve to reduce rates of
      false inference of a major gene, it is also possible to fail to infer a major
      gene when one indeed exists, especially under recessive inheritance.

PMID- 7825594
TI  - Genetic testing and insurance. The Ad Hoc Committee on Genetic Testing/Insurance
      Issues.
AB  - The rapid expansion of opportunities for genetic testing has been accompanied by
      complex questions about the appropriate relationships between providers,
      patients, and insurers. Some of these questions involve large public-policy
      decisions, such as whether the government should guarantee access to health care
      for all citizens. Universal access to health care, without regard to past,
      present, or future risk of disease, could eliminate risk-oriented underwriting in
      health-care coverage. A positive response to that question will ameliorate other
      problems. Until universal access is reality, genetic testing and genetic
      diagnosis will raise important issues for the practicing geneticist. How much
      does a client need to know about insurance implications before consenting to a
      genetic test? Should patients be counseled to purchase insurance before being
      tested? Should genetic information be excluded from medical records before their
      release to insurance companies for routine reimbursements or underwriting? What
      are the ethical and legal responsibilities of the geneticist?

PMID- 7825595
TI  - Inherent intractability of the ascertainment problem for pedigree data: a general
      likelihood framework.
AB  - The problem of ascertainment in segregation analysis arises when families are
      selected for study through ascertainment of affected individuals. In this case,
      ascertainment must be corrected for in data analysis. However, methods for
      ascertainment correction are not available for many common sampling schemes,
      e.g., sequential sampling of extended pedigrees (except in the case of "single"
      selection). Concerns about whether ascertainment correction is even required for
      large pedigrees, about whether and how multiple probands in the same pedigree can
      be taken into account properly, and about how to apply sequential sampling
      strategies have occupied many investigators in recent years. We address these
      concerns by reconsidering a central issue, namely, how to handle pedigree
      structure (including size). We introduce a new distinction, between sampling in
      such a way that observed pedigree structure does not depend on which pedigree
      members are probands (proband-independent [PI] sampling) and sampling in such a
      way that observed pedigree structure does depend on who are the probands (proband
      dependent [PD] sampling). This distinction corresponds roughly (but not exactly)
      to the distinction between fixed-structure and sequential sampling. We show that
      conditioning on observed pedigree structure in ascertained data sets obtained
      under PD sampling is not in general correct (with the exception of "single"
      selection), while PI sampling of pedigree structures larger than simple sibships
      is generally not possible. Yet, in practice one has little choice but to
      condition on observed pedigree structure. We conclude that the problem of genetic
      modeling in ascertained data sets is, in most situations, literally intractable.
      We recommend that future efforts focus on the development of robust approximate
      approaches to the problem.

PMID- 7825596
TI  - Genetic counseling in a Swedish Alzheimer family with amyloid precursor protein
      mutation.

PMID- 7825597
TI  - Nonsyndromic cleft lip and palate: evidence of linkage to a microsatellite marker
      on 6p23.

PMID- 7825598
TI  - Evidence for an association between RFLPs at the transforming growth factor alpha
      (locus) and nonsyndromic cleft lip/palate in a South American population.

PMID- 7825599
TI  - Heterogeneity of the autosomal dominant split hand/split foot malformation.

PMID- 7825600
TI  - Are some apparently simple deletions actually two concerted deletions that result
      from interacting RY(i) hairpin loops?

PMID- 7825601
TI  - Mutations in argininosuccinate synthetase mRNA in Japanese patients, causing
      classical citrullinemia.

PMID- 7825602
TI  - Spectrum of mutations in the gene encoding the adrenoleukodystrophy protein.
AB  - X-linked adrenoleukodystrophy (ALD) has been associated with mutations in a gene
      encoding an ATP-binding transporter, which is located in the peroxisomal
      membrane. Deficiency of the gene leads to impaired peroxisomal beta-oxidation.
      Systematic analysis of the open reading frame of the ALD gene, using reverse
      transcriptase-PCR, followed by direct sequencing, revealed mutations in all 28
      unrelated kindreds analyzed. No entire gene deletions or drastic promoter
      mutations were detected. In only one kindred did the mutation involve multiple
      exons. The other mutations were small alterations leading to missense (13 of 28)
      or nonsense mutations, a single amino acid deletion, frameshifts, or splice
      acceptor-site defects. Mutations affecting a single amino acid were concentrated
      in the region between the third and fourth putative transmembrane domains and in
      the ATP-binding domain. Mutations were detected in all investigated ALD kindreds,
      suggesting that this gene is the only gene responsible for X-linked ALD. This
      overview of mutations is useful in the determination of structurally and
      functionally important regions and provides an efficient screening strategy for
      identification of mutations in the ALD gene.

PMID- 7825603
TI  - Multiple mutations are responsible for the high frequency of metachromatic
      leukodystrophy in a small geographic area.
AB  - Metachromatic leukodystrophy is a lysosomal storage disorder caused by the
      deficiency of arylsulfatase A. The disease occurs panethnically, with an
      estimated frequency of 1/40,000. Metachromatic leukodystrophy was found to be
      more frequent among Arabs living in two restricted areas in Israel. Ten families
      with affected children have been found, three in the Jerusalem region and seven
      in a small area in lower Galilee. Whereas all patients from the Jerusalem region
      are homozygous for a frequent mutant arylsulfatase A allele, five different
      mutations were found in the families from lower Galilee. In patients of Muslim
      Arab origin, we have found a G86-->D, a S96-->L, and a Q190-->H substitution. Two
      different defective arylsulfatase A alleles, characterized by a T274-->M and a
      R370-->W substitution, respectively, have been found among the Christian Arab
      patients. All mutations were introduced into the wild-type arylsulfatase A cDNA.
      No enzyme activity could be expressed from the mutagenized cDNAs after
      transfection into heterologous cells. In all instances, the patients were found
      to be homozygous for the mutations, and four of the five mutations occurred on
      different haplotypes. The clustering of this rare lysosomal storage disease in a
      small geographic area usually suggests a founder effect, so the finding of five
      different mutations is surprising.

PMID- 7825604
TI  - Two new cases of FMR1 deletion associated with mental impairment.
AB  - Screening of families clinically ascertained for the fragile X syndrome phenotype
      revealed two mentally impaired males who were cytogenetically negative for the
      fragile X chromosome. In both cases, screening for the FMR1 trinucleotide
      expansion mutation revealed a rearrangement within the FMR1 gene. In the first
      case, a 660-bp deletion is present in 40% of peripheral lymphocytes. PCR and
      sequence analysis revealed it to include the CpG island and the CGG trinucleotide
      repeat, thus removing the FMR1 promoter region and putative mRNA start site. In
      the second case, PCR analysis demonstrated that a deletion extended from a point
      proximal to FMR1 to 25 kb into the gene, removing all the region 5' to exon 11.
      The distal breakpoint was confirmed by Southern blot analysis and localized to a
      600-bp region, and FMR1-mRNA analysis in a cell line established from this
      individual confirmed the lack of a transcript. These deletion patients provide
      further confirmatory evidence that loss of FMR1 gene expression is indeed
      responsible for mental retardation. Additionally, these cases highlight the need
      for the careful examination of the FMR1 gene, even in the absence of cytogenetic
      expression, particularly when several fragile X-like clinical features are
      present.

PMID- 7825606
TI  - WT1 exon 1 deletion/insertion mutations in Wilms tumor patients, associated with
      di- and trinucleotide repeats and deletion hotspot consensus sequences.
AB  - The WT1 gene is known to play a role in at least some cases of Wilms tumor (WT).
      The first exon of the gene is highly GC rich and contains many short tandem di-
      and trinucleotide repeats, interrupted direct repeats, and CCTG (CAGG) motifs
      that have been identified as hotspots for DNA deletions. We have analyzed 80 WT
      patient samples for mutations in the first exon of WT1, either by SSCP analysis
      of the first 131 bp of the coding portion of WT1 exon 1 or by size analysis of a
      PCR product encompassing the coding region of exon 1 in addition to flanking
      noncoding regions. We report here the occurrence of somatic and germ-line
      deletion and insertion mutations in this portion of the gene in four WT patients.
      The mutations are flanked by short direct repeats, and the breakpoints are within
      5 nt of a CCTG (CAGG) sequence. These data suggest that a distinctive mutational
      mechanism, previously unrecognized for this gene, is important for the generation
      of DNA mutations at the WT1 locus.

PMID- 7825605
TI  - Further elucidation of the genomic structure of PAX3, and identification of two
      different point mutations within the PAX3 homeobox that cause Waardenburg
      syndrome type 1 in two families.
AB  - Waardenburg syndrome is an autosomal dominant disorder characterized by
      sensorineural deafness and pigmentary disturbances. Previous work has linked the
      disease to PAX3 on chromosome 2, and several mutations within the highly
      conserved paired-box and octapeptide motifs, but not the homeobox, have been
      reported. In this report, we have used the published cDNA sequence to further
      define the genomic structure of PAX3, using inverse PCR. We have identified
      exon/intron boundaries between exons 5 and 6 and between exons 6 and 7. Further,
      we have identified the first two mutations within the homeobox in two different
      families with type 1 Waardenburg syndrome. The first is a point mutation (G-->T)
      at the first base of exon 6, which substitutes phenylalanine for valine. In
      another family, we have identified a point mutation (C-->G) within the homebox,
      in exon 6, which substitutes a glycine for arginine at a highly conserved site.
      The homeodomain is important in binding of DNA and in effecting transcriptional
      control. These mutations likely result in structural change within the
      homeodomain that either change the DNA-binding specificity of the homedomain or
      reduce the affinity of the PAX3 protein for DNA. These homeodomain mutations
      should aid in elucidating the role of the homeodomain in the function of the PAX3
      protein.

PMID- 7825609
TI  - Carotid sinus syndrome in the elderly.

PMID- 7825608
TI  - High proportion of new mutations and possible anticipation in Brazilian
      facioscapulohumeral muscular dystrophy families.
AB  - A gene responsible for facioscapulohumeral muscular dystrophy (FSHD) has been
      localized at 4q35. Subsequently, it was found that probe p13E-11 detects a
      polymorphic EcoRI fragment, usually > 28 kb, in normal individuals, whereas in
      sporadic and familial FSHD cases, an EcoRI fragment, usually < 28 kb, was found.
      Although these findings have been amply confirmed, several aspects are as yet
      either controversial or unsolved. In the present investigation, 34 Brazilian FSHD
      families were studied at the clinical and the molecular level for the following
      purposes: to assess the frequency of new mutations and their effect on estimates
      of biological fitness, to characterize FSHD-associated EcoRI fragments detected
      with probe p13E-11 in familial--as compared with isolated--FSHD cases, and to
      assess whether anticipation occurs in multigenerational families. Results from
      our study suggest that new mutations are apparently frequent for FSHD and may
      account for at least one-third of the cases, that somatic mosaicism may not be
      rare, and that biological fitness appeared to be reduced in FSHD, ranging from
      0.6 to 0.82 by different estimates, with no difference in sexes. Interestingly,
      the size of the new EcoRI fragment is apparently smaller in more severely
      affected isolated patients. Moreover, the age at onset of clinical signs, as well
      as the age at ascertainment, in patients from multigenerational families suggests
      that anticipation occurs for FSHD in the majority of the families.

PMID- 7825607
TI  - A 1.5-Mb deletion in 17p11.2-p12 is frequently observed in Italian families with
      hereditary neuropathy with liability to pressure palsies.
AB  - Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal
      dominant disorder characterized by recurrent mononeuropathies. A 1.5-Mb deletion
      in chromosome 17p11.2-p12 has been associated with HNPP. Duplication of the same
      1.5-Mb region is known to be associated with Charcot-Marie-Tooth disease type 1
      (CMT1A), a more severe peripheral neuropathy characterized by symmetrically
      slowed nerve conduction velocity (NCV). The CMT1A duplication and HNPP deletion
      appear to be the reciprocal products of a recombination event involving a repeat
      element (CMT1A-REP) that flanks the 1.5-Mb region involved in the
      duplication/deletion. Patients from nine unrelated Italian families who were
      diagnosed with HNPP on the basis of clinical, electrophysiological, and
      histological evaluations were analyzed by molecular methods for DNA deletion on
      chromosome 17p. In all nine families, Southern analysis using a CMT1A-REP probe
      detected a reduced hybridization signal of a 6.0-kb EcoRI fragment mapping within
      the distal CMT1A-REP, indicating deletion of one copy of CMT1A-REP in these HNPP
      patients. Families were also typed with a polymorphic (CA)n repeat and with RFLPs
      corresponding to loci D17S122, D17S125, and D17S61, which all map within the
      deleted region. Lack of allelic transmission from affected parent to affected
      offspring was observed in four informative families, providing an independent
      indication for deletion. Furthermore, pulsed-field gel electrophoresis analysis
      of SacII-digested genomic DNA detected junction fragments specific to the 1.5-Mb
      HNPP deletion in seven of nine Italian families included in this study. These
      findings suggest that a 1.5-Mb deletion on 17p11.2-p12 is the most common
      mutation associated with HNPP.

PMID- 7825611
TI  - Rise in ANCA titer: to treat or not to treat.

PMID- 7825610
TI  - Aerosolized pentamidine prophylaxis of Pneumocystis carinii pneumonia in HIV
      infected patients.

PMID- 7825612
TI  - Avoiding false-negative results for HTLV-II using new serological assays.

PMID- 7825613
TI  - Didanosine-induced hypertriglyceridemia.

PMID- 7825614
TI  - Post-Salmonella reactive arthritis: late clinical sequelae in a point source
      cohort.
AB  - PURPOSE: To define the natural history of post-Salmonella-infection reactive
      arthritis (ReA) in a point source cohort concurrently exposed to the same
      microorganism, and to determine any relationship between anti-Salmonella humoral
      immune response to the organism and clinical outcome at 5 years. PATIENTS AND
      METHODS: A cohort of 423 Ontario Provincial Police officers with a clinical
      diagnosis of Salmonella food poisoning were defined in 1984. Five years following
      the food poisoning, a mail and telephone survey was carried out to determine all
      those who developed ReA within 3 months of the onset of dysentery. Medical and
      physiotherapy charts from an earlier study on the same cohort were incorporated.
      All patients with a history compatible with reactive arthritis were interviewed
      and examined. Serum was taken to determine the presence of isotypic antibodies to
      the lipopolysaccharide of the causative Salmonella typhimurium. RESULTS: Twenty
      seven of the 423 individuals with dysentery were identified as developing acute
      ReA. In one third of them, the arthritis resolved within 4 months of onset. Two
      thirds continued to have subjective complaints, mostly of minor significance.
      However, symptoms were severe enough to force a change in work for 4 patients.
      Another 4 patients had objective damage to joints radiographically. Objective
      changes to joints were documented on physical examination in 37% of ReA patients
      5 years following onset of disease. IgA antilipopolysaccharide antibodies
      correlated with the severity and duration of disease. Tests of cellular immune
      function did not correlate with clinical variables. CONCLUSIONS: Chronic symptoms
      persist 5 years after the onset of ReA in the majority of patients. Joint damage
      by physical examination and radiographic assessment correlate with functional
      disability. Some early clinical features of disease, including prolonged diarrhea
      during the acute illness, may predict a worse outcome. IgA
      antilipopolysaccharides may serve as a disease marker for late post-Salmonella
      infection ReA.

PMID- 7825616
TI  - Role of intravenous cyclophosphamide in the treatment of severe neuropsychiatric
      systemic lupus erythematosus.
AB  - PURPOSE: We assessed the outcome of 31 patients with severe neuropsychiatric (NP)
      systemic lupus erythematosus (NPSLE) treated with intravenous cyclophosphamide
      (IV-CYC), and identified clinical predictors of response to therapy. METHODS: The
      authors performed a retrospective chart review and classified patients by NP
      manifestation and response to therapy as measured by serial anatomic imaging and
      neurodiagnostic studies coupled with clinical assessment of improvement. RESULTS:
      Neuropsychiatric manifestations occurred with the following frequencies: organic
      brain syndromes (OBS) 55%, stroke syndromes 35%, peripheral or mononeuropathy
      32%, seizures 29%, psychiatric symptoms 26%, transverse myelitis 16%, cranial
      neuropathies 13%, other 16%. Most patients had multiple NP manifestations, with a
      median of two. Ninety percent of patients had failed therapy with corticosteroids
      with or without cytotoxic drugs prior to treatment with IV-CYC. Eight patients
      received synchronous plasmapheresis along with IV-CYC. After treatment with IV
      CYC, NP deficits substantially improved in 61% (group I), stabilized in 29%
      (group S), and progressively deteriorated in 10% (group P). Patients in group I
      had significantly fewer NP manifestations than combined group S+P, two versus
      four, and a lower frequency of OBS, 37% versus 83%. CONCLUSION: Intravenous
      cyclophosphamide appears to be an effective treatment for some patients with
      severe NPSLE refractory to other forms of therapy. Higher number of NP
      manifestations and presence of OBS may predict poor outcome and identify a group
      of patients for whom early aggressive therapy may be indicated.

PMID- 7825615
TI  - Blood glucose estimation and symptoms during hyperglycemia and hypoglycemia in
      patients with insulin-dependent diabetes mellitus.
AB  - PURPOSE: To investigate hypoglycemic and hyperglycemic symptoms, accuracy of
      estimating blood glucose, and their relation to glycemic control and
      counterregulatory hormone levels in insulin-dependent diabetes mellitus. PATIENTS
      AND METHODS: During randomly ordered stepped hypoglycemic and hyperglycemic
      insulin clamps on two separate days, 42 patients with insulin-dependent diabetes
      mellitus rated the intensity of 40 moods and symptoms when glucose was 8.9, 5.6
      and 2.2 mmol/L, and 8.9, 14.4 and 21.1 mmol/L. The subjects were blinded to their
      actual glucose levels and asked to estimate them at each step. Epinephrine,
      norepinephrine, cortisol, growth hormone, and glucagon were measured at each
      glucose plateau. RESULTS: Cluster analysis yielded five symptom groups during
      hypoglycemia: autonomic symptoms, negative moods, positive moods, feeling
      weak/dizzy, and feeling relaxed. At 2.2 mmol/L, mean scores for all five symptom
      groups and 11 of 17 unclustered symptoms differed from those reported at the
      baseline glucose of 8.9 mmol/L (P < or = 0.05), but 34% of patients reported no
      awareness of autonomic symptoms. The intensity of autonomic symptoms correlated
      positively with HbA1 (r = .43, P < 0.01), epinephrine (r = .59, P < 0.001),
      norepinephrine (r = .45, P < 0.01) and cortisol (r = .62, P < 0.001), and
      negatively with glucose estimation error (r = -.45, P = 0.01). Six patients (15%)
      were unaware of both autonomic and neuroglycopenic symptoms during hypoglycemia.
      At 21.1 mmol/L, only 5 of 40 symptoms differed (P < 0.05) from baseline.
      Seventeen percent of subjects made potentially serious errors when estimating
      glucose at 2.2 mmol/L, and 66% at 21.1 mmol/L. Many patients experienced symptoms
      different from those they reported as their usual manifestations of changing
      glucose levels. CONCLUSIONS: Since the majority of patients made clinically
      serious errors in glucose estimation, and many used symptoms that did not
      discriminate hyperglycemia and hypoglycemia, individualized training to increase
      awareness of glucose-related symptoms and glucose levels may help patients reduce
      the frequency or severity of hyperglycemic and hypoglycemic events.

PMID- 7825617
TI  - Osler's maneuver: absence of usefulness for the detection of pseudohypertension
      in an elderly population.
AB  - PURPOSE: To investigate the prevalence and clinical relevance of Osler's maneuver
      for detecting pseudohypertension in the elderly. PATIENTS AND METHODS: Osler's
      maneuver was performed by one investigator in 205 consecutive inpatients of a
      French geriatric hospital (40 men and 165 women; mean age 84.2 +/- 6.2 years). In
      12 Osler-positive and 12 Osler-negative patients matched for age, sex, and
      presence of hypertension, the blood pressure values measured directly at the
      radial artery were compared to those measured indirectly with a standard mercury
      sphygmomanometer. Aortic and upper limb pulse wave velocities (PWV) were also
      measured in these 24 patients. RESULTS: Twenty-three of 205 patients (11%) were
      Osler-positive. Age, sex ratio, and prevalence of hypertension or other
      cardiovascular diseases did not differ significantly in Osler-positive and Osler
      negative patients. Systolic blood pressure (SBP), measured by standard mercury
      sphygmomanometer, was significantly greater in Osler-positive than Osler-negative
      patients (157 +/- 37 versus 132 +/- 28 mm Hg; P < 0.01). Diastolic blood pressure
      (DBP) did not differ significantly (78 +/- 18 versus 74 +/- 14 mm Hg).
      Interobserver agreement concerning Osler's sign, studied in 40 patients, was good
      (kappa = 0.72). In 12 Osler-positive and 12 Osler-negative patients, the mean
      differences between SBP obtained by cuff-manual indirect blood pressure and
      direct measurements were -3.71 +/- 22.85 mm Hg and -8.59 +/- 14.40 mm Hg (P =
      NS). For DBP, these differences were 18.40 +/- 15.72 and 12.01 +/- 5.80 mm Hg (P
      = NS). The differences between the indirect and direct blood pressure
      measurements were significantly correlated to upper limb PWV, but not aortic PWV,
      for both SBP and DBP. Pseudohypertension, defined as the indirect measurement
      overestimation of SBP or DBP by 10 mm Hg or more, was found in 15 of the 24
      patients (63%). In these patients, upper limb PWV was significantly greater than
      in those with no pseudohypertension (7.0 +/- 2.2 versus 5.4 +/- 1.3 m/s; P <
      0.05). CONCLUSION: The Osler-positive maneuver is frequently found in elderly
      hospital inpatients, but its ability to detect pseudohypertension in clinical
      practice is poor. Measurement of upper limb PWV might be a more appropriate way
      of screening for this condition.

PMID- 7825618
TI  - The other fifty percent.

PMID- 7825619
TI  - Ambulatory evaluation of nephrolithiasis: an update of a 1980 protocol.
AB  - Evaluations of 1,270 patients with recurrent nephrolithiasis in an outpatient
      setting were analyzed for the purpose of updating the classification of
      nephrolithiasis. All but 4% had abnormal urinary biochemistry that placed them
      into one or more of 20 etiologic categories. A single diagnosis was documented in
      41.3% of patients. The remaining 58.7% had more than one diagnosis.
      Hypercalciuric calcium (Ca) nephrolithiasis, encountered in 60.9% of patients,
      comprised six variants--absorptive hypercalciuria Type I and II, renal
      hypercalciuria, primary hyperparathyroidism, and unclassified hypercalciuria
      (renal phosphate leak and fasting hypercalciuria). Hyperuricosuria Ca
      nephrolithiasis (HUCN) and gouty diathesis (GD) accounted for 35.8% and 10.0% of
      patients, respectively. Distinguishing features were hyperuricosuria and normal
      urinary pH in HUCN, and normal urinary uric acid and low urinary pH (< 5.5) in
      GD. Hyperoxaluric Ca nephrolithiasis, occurring in 8.1% of patients, was
      subdivided into enteric, primary, and dietary variants. Hypocitraturic Ca
      nephrolithiasis affected 28% of patients in its idiopathic variant. Many of these
      patients' problems were probably dietary in origin, while some could have had
      incomplete renal tubular acidosis. Hypocitraturia due to renal tubular acidosis
      or chronic diarrheal syndrome affected only 3.3% of patients. Hypomagnesiuric Ca
      nephrolithiasis, infection stones, and cystinuria were uncommon, accounting for
      6.8%, 5.9%, and 0.9% of patients, respectively. The acquired problem of low urine
      volume (< 1 L/d) was found in 15.3% of patients. The remaining 3.5% of patients
      were difficult to classify despite the presence of abnormal urinary biochemistry.

PMID- 7825620
TI  - Plasma cell proliferation in monoclonal gammopathy: relations with other biologic
      variables--diagnostic and prognostic significance.
AB  - PURPOSE: We investigated the place of direct plasma cell proliferation analysis
      beside other biologic data in monoclonal gammopathy, particularly the serum level
      of C-reactive protein (C-RP) PATIENTS: Eighty patients were studied at the time
      of their diagnosis. Patients with a serum creatinine level greater than 200
      mumol/L were excluded. METHODS: Plasma cell proliferation analysis was performed
      after bromodeoxyuridine incorporation and double immunoenzymatic labeling on
      cytological smears, making determination of the plasma cell labeling index (LI)
      possible. The other biologic variables studied were related to tumor burden
      (plasmacytosis, hemoglobin, serum levels of monoclonal immunoglobulin, albumin)
      or to kidney function (creatinine). beta 2-microglobulin (beta 2-M), C-RP, lactic
      dehydrogenase (LDH), and calcemia were also assessed. RESULTS: No correlation was
      found between LI and serum C-RP. LDH was the sole variable significantly
      correlated to C-RP (P < 0.01). Besides the biologic parameters used for the
      staging according to the Durie and Salmon classification, beta 2-M, albumin and
      LI were significantly different between stages (P < 0.0002, < 0.0004, < 0.00001).
      LDH and C-RP showed no significant difference. Results were similar when patients
      with and without bone lesions were analyzed separately. Multivariate analysis
      ranked these variables as follows with respect to prognostic value: beta 2-M, LI,
      and age. CONCLUSION: Among the variables analyzed, LI is the sole true reflector
      of cell proliferation. We confirm its diagnostic and prognostic value.

PMID- 7825621
TI  - Outcome of protein-energy malnutrition in elderly medical patients.
AB  - PURPOSE: To assess the impact of protein-energy malnutrition (PEM) on mortality
      and the long-term variations in the nutritional status of subjects admitted as
      emergency cases in a 9-month prospective follow-up study. PATIENTS AND METHODS:
      The study comprised 205 patients without cancer aged 75 years (+/- 1).
      Malnourished subjects were identified as having at least three nutritional
      variables (which included weight index, triceps skinfold thickness, arm muscle
      circumference, serum albumin, and delayed cutaneous hypersensitivity reaction)
      below the reference range. RESULTS: The mortality was 44% in the 41 malnourished
      patients and 18% in the 164 nonmalnourished subjects (P < 0.001). Among
      malnourished patients with congestive heart failure the mortality was 80%.
      Multivariate analysis revealed congestive heart failure, multiple organ disease,
      and PEM to be predictors of death. When the interaction between these disorders
      and PEM was considered, the prognostic relevance of PEM remained among the
      patients with cardiac congestion. Of the surviving subjects, 125 were reexamined
      after 9 months. At admission, more than half of the patients had displayed
      elevated levels of serum acid glycoprotein as evidence of an ongoing inflammation
      and subnormal recordings for serum albumin and delayed cutaneous
      hypersensitivity. At the reexamination, these variables had normalized in the
      well-nourished patients and in the 9 patients who had recovered from PEM, but
      remained unchanged in the 10 patients with persistent PEM. The latter patients
      were severely malnourished, commonly infected, and often hospitalized.
      CONCLUSIONS: Protein-energy malnutrition in noncancer medical patients is
      associated with an excess mortality in those with congestive heart failure.
      Improvement of PEM is accompanied by a decline in inflammatory activity.

PMID- 7825622
TI  - Categorical medicine residents' experiential curriculum.
AB  - PURPOSE: To assess the case mix or experiential curriculum of a university-based
      categorical medicine residency program and compare the residents' continuity
      clinic case mix with the outpatients seen by practicing internists. PATIENTS AND
      METHODS: Descriptive study during the 1991-1992 academic year of 24,218
      inpatients and outpatients from the University of California, San Francisco,
      Department of Medicine's three core hospitals: the University of California, San
      Francisco Hospital; the Department of Veterans Affairs Medical Center; and the
      San Francisco General Hospital. The diagnoses and ages of patients who made
      office visits to practicing internists from the National Ambulatory Medical Care
      Survey (NAMCS) were compared with corresponding data from the categorical
      medicine residents' continuity clinic patients. RESULTS: Seventy percent of the
      general medicine inpatients at the three core hospitals had one of the 25 most
      common principal diagnoses for inpatients. Eighty-seven percent of the patients
      seen by the residents in their continuity clinic had one of the 20 most common
      diagnoses seen by practicing internists in the NAMCS. The age distribution was
      similar in both groups. CONCLUSIONS: A systematic assessment of clinical training
      at one university-based hospital program shows that common internal medicine
      problems represent the case mix of the great majority of patients, both
      inpatients and outpatients, seen by categorical medicine residents. Residents'
      continuity clinic patients are similar to patients seen by practicing internists.
      The program's challenge is to ensure that residents have adequate time with
      general medicine experiences, both in the inpatient setting and in the ambulatory
      and longitudinal care settings, while balancing and integrating these activities.

PMID- 7825623
TI  - Alterations in carbohydrate metabolism during stress: a review of the literature.
AB  - Patients with sepsis, burn, or trauma commonly enter a hypermetabolic stress
      state that is associated with a number of alterations in carbohydrate metabolism.
      These alterations include enhanced peripheral glucose uptake and utilization,
      hyperlactatemia, increased glucose production, depressed glycogenesis, glucose
      intolerance, and insulin resistance. The hypermetabolic state is induced by the
      area of infection or injury as well as by organs involved in the immunologic
      response to stress; it generates a glycemic milieu that is directed toward
      satisfying an obligatory requirement for glucose as an energy substrate. This
      article reviews experimental and clinical data that indicate potential mechanisms
      for these alterations and emphasizes aspects that have relevance for the
      clinician.

PMID- 7825624
TI  - Fever, cough, and dyspnea in a 38-year-old man with acquired immunodeficiency
      syndrome.

PMID- 7825625
TI  - The floating Zepitos.

PMID- 7825626
TI  - My Own Country.

PMID- 7825627
TI  - International hero.

PMID- 7825628
TI  - Catheter-related venous thrombosis.

PMID- 7825629
TI  - The androgenicity of progestins.
AB  - All steroid hormones are structurally similar, but relatively minor differences
      cause profound alterations in biochemical activity. The 21-carbon series
      (pregnane nucleus) includes the corticoids and the true progestins (e.g.,
      medroxyprogesterone acetate). The 19-carbon series (androstane nucleus) includes
      all the androgens, among them the progestins used in most oral and parenteral
      contraceptives. The removal of carbon 19 from testosterone changes the major
      hormonal effect from androgenic to progestogenic, but these "19-nor" steroids
      retain varying degrees of androgenic activity. (They can also have limited
      estrogenic activity, but this is insignificant at the low doses used for
      contraception.) Some of the 19-nortestosterone progestins are metabolized to
      other compounds (e.g., norethynodrel, ethynodiol diacetate, and lynestrenol to
      norethindrone), and some (levonorgestrel, desogestrel) are active unchanged. The
      lingering androgenic effects of 19-nor progestins are dose-related, opposed by
      estrogen, and are manifested metabolically (e.g., glucose tolerance, lipoprotein
      synthesis) and symptomatically (e.g., acne, weight gain). The effect of 19
      nortestosterones on lipoproteins prompted the development of less androgenic
      compounds, but the obvious benefit of the new progestins (desogestrel, gestodene,
      norgestimate) is a reduction in the symptoms associated with the androgenicity of
      the older compounds. Mitigation of androgenic effects on lipoprotein and
      carbohydrate metabolism could have long-term benefits, especially for women who
      are at risk of arteriosclerotic vascular disease; however, these effects remain
      to be epidemiologically demonstrated.

PMID- 7825630
TI  - Androgens and sexuality.
AB  - A review of the literature reveals that the endocrine determinants of female
      sexuality are complex and difficult to characterize. In adolescent males, free
      testosterone directly affects sexual motivation, with social factors exerting
      little or no effect. In adolescent girls, by contrast, societal and peer pressure
      play a pivotal role in the appearance of certain sexual behaviors. Throughout a
      woman's life, hormonal and psychosocial factors are critical influences. It is
      possible that cyclic patterns of testosterone are less important for female
      sexual behavior than the "tonic" effect of overall testosterone levels. Although
      the estrogen dependence of the vaginal epithelium--important for postmenopausal
      women--has been clearly established, the role of other hormonal factors and
      treatments, particularly those involving androgens, in human female sexual
      behavior remains enigmatic. The search for an understanding of these
      relationships is not merely an interesting academic exercise but is necessary to
      determine what role, if any, androgens may play in the treatment of sexual
      dysfunction during the female reproductive years.

PMID- 7825631
TI  - Androgenic effects of oral contraceptives: implications for patient compliance.
AB  - Androgenic disorders have many negative physical effects. These effects may be
      caused by excess androgen (exogenous or endogenous) or by end-organ sensitivity
      to normal levels of androgens. Historically, androgenic progestins in oral
      contraceptives have also been associated with some of these negative effects. The
      most apparent signs of androgen excess are the external manifestations, including
      oily skin, acne, hirsutism, android obesity, and androgenic alopecia. Of equal
      concern are the potential metabolic disturbances associated with
      hyperandrogenicity. Unfavorable lipid profiles and increased incidence of
      diabetes and hypertension are very real threats to long-term health. In oral
      contraceptive users, external manifestations of androgenicity often lead to poor
      compliance, decreased efficacy, and discontinuation of oral contraceptive use,
      especially in the younger patient. With the introduction of the newer oral
      contraceptive formulations containing less androgenic progestins (norgestimate,
      desogestrel, gestodene), androgen-related effects have been reduced and better
      compliance is anticipated.

PMID- 7825632
TI  - Androgenic disorders of women: diagnostic and therapeutic decision making.
AB  - Women with androgenic disorders usually seek medical attention to ameliorate the
      effects of androgens on appearance or on fertility, less commonly for
      oligomenorrhea or for prevention of metabolic complications. These conditions
      affect at least 5-10% of women and can be very disturbing to the affected woman.
      Careful attention to possible androgenic changes is necessary when performing
      physical examination because changes are often concealed. Treatment for skin and
      hair changes depends less on the nature of the changes than on the underlying
      endocrine causation. The two endocrine factors are androgen levels and receptor
      sensitivity. The latter is a factor in all androgenic changes, and therapy is
      rarely successful without use of medication to block androgen receptors. If
      androgen levels are even minimally elevated, suppression of the source gland-
      ovary or adrenal--is appropriate. Ovarian suppression is usually by means of an
      oral contraceptive; for adrenal suppression, a glucocorticoid is effective.
      Response to medical therapy of androgenic disorders is slow; physicians and
      patients must be willing to wait weeks, or months, for the beginning of
      improvement. Endocrine therapy does not seem to help associated diabetes or
      dyslipidemia. Overall, medical therapy of androgenic disorders is more effective
      than generally recognized. The principal pitfalls are failing to select
      medication based on the specific endocrine disturbance and failing to wait long
      enough for improvement to appear. Side effects do occur but are generally
      uncomfortable or inconvenient rather than dangerous. Treatment is highly
      rewarding, however, for there are few situations in medicine in which treatment
      is so appreciated by the patient.

PMID- 7825633
TI  - The role of oral contraceptives in the treatment of hyperandrogenic disorders.
AB  - The clinical manifestations associated with hyperandrogenism, such as hirsutism
      and acne, are disturbing to most patients. In addition to correcting androgen
      related problems, concerns such as contraception or other metabolic problems (for
      example, lipid/lipoprotein abnormalities, diabetes, hypertension) associated with
      these disorders and the effects of unopposed estrogen on the endometrium also
      need to be considered. Oral contraceptives are a therapeutic modality that may
      address these multiple problems. The potential mechanisms of action by which oral
      contraceptives correct excess androgen states include gonadotropin suppression,
      reduction of circulating androgens, increased androgen binding, suppression of
      adrenal androgen secretion and inhibition of 5 alpha-reductase, and androgen
      receptor binding. In normal women, there is good evidence that these actions
      occur with the use of oral contraceptives. Among women with anovulatory
      hyperandrogenic states, such as polycystic ovary syndrome, the response to oral
      contraceptives in each of these areas is somewhat more variable. However, oral
      contraceptive preparations that are more estrogen dominant appear to produce many
      of the desired effects. From a clinical standpoint, 60-100% of women with
      hirsutism improve on oral contraceptives; acne shows improvement in a high
      percentage of women as well. The use of oral contraceptives also reduces the risk
      of endometrial hyperplasia that may be associated with anovulatory states.
      Finally, current low-dose preparations containing the newer progestins (for
      example, norgestimate and desogestrel) appear to be either neutral, or perhaps
      beneficial, with respect to their metabolic impact.

PMID- 7825634
TI  - Effects of sex steroids on women's health: implications for practitioners.
AB  - Androgen excess in women is manifested typically by clinical features that may
      include hirsutism, acne, central obesity, male-pattern baldness, upper torso
      widening, increased waist-to-hip ratio, clitoral hypertrophy, and deepening of
      the voice. The differential diagnosis includes androgen-producing ovarian and
      adrenal neoplasms, Cushing's syndrome, polycystic ovary syndrome, and the intake
      of exogenous androgens. Physicians treating patients for one symptom of androgen
      excess must be alert for other symptoms and signs. The cosmetic manifestations of
      androgen excess belie the serious health risks associated with this condition,
      including cardiovascular disease, intravascular thrombosis, and insulin
      resistance. Prompt clinical recognition of androgen excess, understanding of the
      androgen-related biochemical abnormalities underlying the risks associated with
      this condition, and implementation of risk modification can reduce the incidence
      of associated morbidity and mortality. An interdisciplinary approach to
      management is strongly recommended. Risk reduction strategies include correction
      of dyslipidemias, low-dose aspirin for primary prevention of myocardial
      infarction, maintenance of ideal weight, smoking cessation, exercise, use of oral
      contraceptives containing a low-androgenic progestin, and postmenopausal estrogen
      replacement. Combination oral contraceptives containing low-androgenic progestins
      are effective not only in reducing signs of androgen excess but also in
      potentially retarding the progression of long-term sequelae such as
      cardiovascular disease.

PMID- 7825636
TI  - Steroid 21-hydroxylase deficiency (congenital adrenal hyperplasia).
AB  - Congenital adrenal hyperplasia, caused by any one of a number of inborn errors of
      steroidogenesis in which cortisol is not sufficiently produced by the adrenal
      cortex, is in most cases due to a deficiency of the enzyme steroid 21
      hydroxylase. Classic 21-hydroxylase deficiency occurs in about 1 in 14,000 live
      births. In classic 21-hydroxylase deficiency, the most common cause of genital
      ambiguity in females, prenatal exposure to excess androgens results in
      virilization of the female fetus. Newborn males have normal genitalia.
      Postnatally, untreated females as well as males present with signs of androgen
      excess. Three fourths of classic 21-hydroxylase deficiency cases do not
      effectively synthesize aldosterone and are salt-wasting, a condition that is
      potentially fatal. An allelic variant of classic 21-hydroxylase deficiency,
      termed nonclassic 21-hydroxylase deficiency, is associated with a milder
      enzymatic defect and no genital ambiguity at birth, but postnatal virilization
      may be seen. The 21-hydroxylase enzyme, a cytochrome P450 hemeprotein (cytochrome
      P450c21), is encoded by the gene CYP21, which has a closely neighboring
      homologous pseudogene, CYP21P. Mutations in the CYP21 gene, causing 21
      hydroxylase deficiency, are common and occur owing to two mechanisms: gene
      deletion and apparent gene conversion. Prenatal diagnosis is important to
      identify a fetus affected with 21-hydroxylase deficiency. Genital ambiguity in
      affected females can be prevented by proper administration of dexamethasone to
      the pregnant mother. Postnatally, the treatment of 21-hydroxylase deficiency is
      lifelong hormonal replacement. With carefully supervised medical treatment,
      congenital adrenal hyperplasia patients have the capacity for normal puberty and
      fertility.

PMID- 7825635
TI  - Clinical relevance of testosterone and dihydrotestosterone metabolism in women.
AB  - Androgens are part of normal female physiology. When they are secreted in excess
      or when they cause unwanted symptoms such as hirsutism and male-pattern baldness,
      the term hyperandrogenism is used. In many hyperandrogenic women, there is no
      well-defined hormonal abnormality, but the women are simply on one end of a
      normal spectrum of androgen secretion and cutaneous androgen sensitivity. To be
      active in the skin, testosterone must be converted to dihydrotestosterone by the
      enzyme 5 alpha-reductase. Androgen sensitivity is determined, in part, by 5 alpha
      reductase activity in the skin. This is a localized phenomenon, and there is no
      generalized increase in 5 alpha-reductase activity in these women.
      Dihydrotestosterone can be converted to glucuronide and sulfate conjugates,
      including androstanediol glucuronide. These androgen conjugates have been
      proposed to be serum markers of cutaneous androgen metabolism, but recent
      evidence indicates that they arise from adrenal precursors and are more likely to
      be markers of adrenal steroid production and metabolism. Antiandrogens (androgen
      receptor blockers) are the best medical treatment of cutaneous hyperandrogenism.
      5 alpha-Reductase inhibitors have recently been approved for the treatment of
      benign prostatic hyperplasia, and research is currently underway to determine
      their effectiveness in treating hirsutism and male-pattern baldness.

PMID- 7825637
TI  - Androgens and women's health: genetic and epidemiologic aspects of lipid
      metabolism.
AB  - Lipoprotein metabolism may be viewed as a process whereby large, triglyceride
      carrying particles from the intestine and liver are broken down into smaller
      cholesterol-enriched lipoprotein particles. In the process, triglyceride is
      transported from the intestine and liver to adipose and other storage tissues.
      Androgen appears to affect lipoprotein metabolism in a number of ways. These
      include: increasing the activity of lipoprotein lipase and hepatic triglyceride
      lipase, resulting in higher levels of triglyceride in adipose tissue and a drop
      in total circulating high-density lipoprotein levels, respectively, and
      decreasing catabolic removal of low-density lipoproteins from circulating plasma.
      In pre- and postmenopausal women, androgen progestins in some oral
      contraceptives, especially the older 19-nortestosterone derivatives such as
      norgestrel, lower high-density lipoprotein and raise low-density lipoprotein
      levels. Newer 19-nortestosterone derivatives, such as desogestrel and
      norgestimate, have a lesser effect on circulating lipoproteins. Nonoral
      androgenic progestins (e.g., subcutaneous norgestrel) have little effect on
      circulating lipids, however, which indicates the significance of the "first pass"
      through the liver for oral agents. The effects of androgens on atherogenesis are
      largely unexplored, although preliminary studies indicate that they may promote
      the atherogenic process.

PMID- 7825638
TI  - Obesity, lipids, cardiovascular risk, and androgen excess.
AB  - Several lines of evidence suggest that a subset of women may be at increased risk
      of cardiovascular disease because of unfavorable alterations in insulin action
      and/or production, accompanying altered apolipoprotein metabolism and altered
      androgenicity and/or estrogenicity. A number of cardiovascular disease risk
      factors, including central obesity, insulin resistance (with associated
      hyperinsulinemia), dyslipidemia, and/or diabetes mellitus, tend to cluster in
      these women. Another common ovarian morphology in women with hyperandrogenism is
      polycystic ovaries, which cluster with hirsutism, anovulation, infertility,
      gonadotropin secretion abnormalities, android fat distribution, and many
      important cardiovascular disease risk factors. Studies indicate that androgen
      excess may be a signal of increased risk for coronary artery disease, even in
      younger women. If androgenicity and insulin resistance are early warning signs of
      increasing risk of morbidity and mortality, these patients are prime candidates
      for preventive medicine. It is important that primary care providers begin to
      recognize these androgen disorders as a clue to the existence of a complex,
      lifelong pattern potentially placing women at risk for premature morbidity and
      mortality and initiate preventive treatment before irreversible thresholds are
      crossed.

PMID- 7825639
TI  - Hyperandrogenic anovulation (PCOS): a unique disorder of insulin action
      associated with an increased risk of non-insulin-dependent diabetes mellitus.
AB  - Polycystic ovary syndrome is the most common endocrine disorder in women of
      reproductive age. Recent prevalence estimates suggest that 5-10% of premenopausal
      women have the full-blown syndrome of hyperandrogenism, chronic anovulation, and
      polycystic ovaries. Evidence suggests that women with polycystic ovary syndrome
      have a unique disorder of insulin action and are at increased risk to develop non
      insulin-dependent diabetes mellitus. Further, non-insulin-dependent diabetes
      mellitus in women with polycystic ovary syndrome has a substantially earlier age
      of onset (third to fourth decades) than it does in the general population (sixth
      to seventh decades). Studies assessing whether abnormalities in insulin action
      are intrinsic or secondary to the hormonal milieu have found that insulin-induced
      receptor autophosphorylation is markedly diminished in approximately 50% of
      polycystic ovary syndrome women. This defect is unique to women with polycystic
      ovary syndrome and is not seen in other common insulin-resistant states of
      obesity and non-insulin-dependent diabetes mellitus. In polycystic ovary syndrome
      women who have normal receptor autophosphorylation, it remains likely that
      signaling mechanisms downstream of the receptor are abnormal, since these women
      are also insulin resistant. This distinctive post-insulin-binding defect appears
      to be genetic, since it is present in cells removed from the in vivo environment
      for generations.

PMID- 7825640
TI  - Endogenous sex hormones: impact on lipids, lipoproteins, and insulin.
AB  - Estrogen use has been reported to decrease triglyceride and low-density
      lipoprotein cholesterol (LDL-C) and increase high-density lipoprotein cholesterol
      (HDL-C). Estrogen use increases the secretion of large, very low-density
      lipoprotein cholesterol (VLDL-C) and also stimulates the uptake of VLDL-C by the
      liver and increases the catabolism of LDL-C in the liver. Sex hormones may affect
      several enzymes involved in the metabolism of HDL-C and triglyceride and may also
      affect lipolysis. In both pre- and postmenopausal women, several studies have
      shown that increased glucose and insulin concentrations are associated with
      increased free testosterone and decreased sex hormone binding globulin. The
      temporal direction of this relationship in premenopausal women is not clear,
      however. In contrast to women, increased androgen concentrations in men do not
      seem to be associated with increased cardiovascular risk factors, although
      testosterone concentrations are associated with increased HDL-C and decreased
      insulin concentrations. Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone
      sulfate (DHEAS) appear to be associated with improved cardiovascular risk factors
      in men, but this connection in women is less clear.

PMID- 7825641
TI  - The insulin-like growth factor system in normal and abnormal human ovarian
      follicle development.
AB  - Intraovarian peptides synergize with and potentiate gonadotropin actions in
      ovarian follicular development. The insulin-like growth factor system is one of
      several growth factor systems that regulate a variety of processes in ovarian
      granulosa and theca cells. Insulin-like growth factor binding proteins, which
      generally inhibit insulin-like growth factor action, are high in androgen
      dominant but not estrogen-dominant follicles, and these insulin-like growth
      factor binding proteins may limit the co-gonadotropic actions of insulin-like
      growth factors within the follicle. Evidence is accumulating that insulin-like
      growth factor binding proteins within estrogen-dominant follicles are regulated
      by decreased production and by increased degradation. In polycystic ovary
      syndrome, in which follicles are at an arrested stage of maturation, insulin-like
      growth factor I and follicle stimulating hormone levels are normal and yet there
      is an accumulation of androstenedione substrate. Aromatase activity can be
      activated when granulosa are isolated from the polycystic ovary syndrome follicle
      but is not active in the follicle in situ. High levels of insulin-like growth
      factor binding proteins are present and likely inhibit insulin-like growth factor
      action in this arrested stage of development. Whether they contribute to it
      directly or reflect the androgen-dominant state of the follicle is not known at
      this time. Insulin resistance in polycystic ovary syndrome may result from
      insulin acting on surrogate receptors, like the insulin-like growth factor
      receptor, although the precise roles of insulin and the insulin-like growth
      factor system in the pathogenesis of polycystic ovary syndrome and associated
      states of hyperandrogenism remain to be defined.

PMID- 7825642
TI  - Reproductive health and polycystic ovary syndrome.
AB  - Women with hyperandrogenic disorders represent a unique group among those with
      infertility due to anovulation. Although antiestrogens are effective in restoring
      ovulation in most women, it remains unclear whether these treatments restore
      fecundability per ovulatory cycle and the ability to maintain pregnancy in these
      individuals. Moreover, antiestrogens are ineffective in restoring ovulation in
      some hyperandrogenic anovulatory women, whose condition poses unique and vexing
      challenges for the infertility therapist. Gonadotropin treatment in antiestrogen
      resistant women often leads to ovarian hyperstimulation syndrome, which has been
      addressed by modification of dosing schedules (e.g., low-dose administration),
      pretreatment with gonadotropin-releasing hormone (GnRH) analogs, and elimination
      of luteinizing hormone from the administered gonadotropins. Surgical reduction in
      ovarian volume has met with some success, although there may be a risk of
      inducing surgical adhesions of the adnexa. The second major reproductive
      adversity facing these patients is their elevated risk of endometrial cancer.
      Unopposed estrogen exposure probably contributes to this risk, but
      hyperandrogenicity and hyperinsulinism may act independently or in concert with
      estrogen to amplify the risk in these women. While the risks and strategies for
      preventive care in these women need to be better defined, reproductive health
      specialists are urged to continue using presently accepted measures, including
      education, to maintain these women's reproductive health.

PMID- 7825643
TI  - Exogenous androgens in postmenopausal women.
AB  - There is an increasing awareness that androgens are of therapeutic value in
      postmenopausal women. Evidence is emerging demonstrating the role of testosterone
      in both female embryologic development and normal sexual behavior and mood. Women
      who are androgen depleted develop physical and behavioral symptoms referred to as
      female androgen deficiency syndrome. To a lesser degree, women who undergo an
      oophorectomy are deprived of endogenous ovarian androgens and have consistently
      been shown to have impairment of sexual functioning, loss of energy, depression,
      and headaches. Testosterone seems to act synergistically with estrogen in the
      treatment of these symptoms. The combination of estradiol and testosterone has
      been shown to have a beneficial effect on the skeleton, although not
      significantly better than estradiol therapy alone. Cosmetic side effects are rare
      if supraphysiologic doses are avoided. The potential metabolic complications have
      not been consistently demonstrated in studies to date. Androgen replacement
      therapy is a neglected area of medical practice and further research is needed to
      identify all women who will benefit from it since studies in menopausal women
      have shown parenteral administration to be well tolerated and safe. Such therapy
      is underused and very much underresearched. While testosterone implants work
      adequately, it would be more desirable and convenient to use a testosterone patch
      and safer, more effective oral androgens, if these products were available.

PMID- 7825644
TI  - Role of androgens in the developmental biology of the pilosebaceous unit.
AB  - The growth and development of pilosebaceous units in their characteristic pattern
      depends on the interaction of androgens and diverse biologic factors. Stromal
      epithelial interactions are essential features. Considerable evidence suggests
      that androgens stimulate the growth of sensitive pilosebaceous units primarily by
      acting on specific stromal cells and that androgens and retinoic acid interact to
      regulate specific stages of sebocyte differentiation.

PMID- 7825645
TI  - Hormonal correlates of acne and hirsutism.
AB  - Acne is a multifactorial disorder reflecting the role of infection, abnormal
      keratinization and immunologic reaction, as well as hormonal influences, on the
      pilosebaceous unit. Clinical studies have correlated elevated levels of
      androgens, originating in both the adrenal glands and ovaries, with acne. These
      include total and free testosterone, delta 4-androstenedione,
      dehydroepiandrosterone and its sulfate, and low levels of sex hormone binding
      globulin. The pathogenesis of acne initiation in childhood has been linked to
      rising serum levels of dehydroepiandrosterone sulfate. Hirsutism has been more
      directly correlated with increased levels of serum androgens, notably free
      testosterone. Underlying causes of elevated androgens in both disorders include
      very rare tumors, partial or late-onset forms of congenital adrenal hyperplasia,
      developmental adrenal abnormalities and, most commonly, polycystic ovary
      syndrome. Early acne treatment may include topical benzoyl peroxide, antibiotics,
      and tretinoin. More severe disease can be treated systemically (with antibiotics
      and/or isotretinoin). Very-low-dose corticosteroids can be used to eliminate the
      adrenal component of hyperandrogenism. Oral contraceptives, especially those that
      contain low-androgenic progestins, can reduce excessive androgens from any source
      and specifically suppress the ovary in polycystic ovary syndrome. Gonadotropin
      releasing hormone agonists, with or without estrogen supplementation, and
      systemic or topical antiandrogens may play a more important role in the future.

PMID- 7825646
TI  - The genetics of polycystic ovary syndrome.
AB  - Problems that confound the clinical characterization of polycystic ovary syndrome
      (PCOS) also complicate the search for its genetic cause. There is no consensus as
      to the nature of the clinical phenotype for PCOS, and there is even doubt whether
      polycystic ovaries are an indispensable part of the syndrome. Few ethnic studies
      on PCOS have been performed, although it has been reported in most major racial
      groups. Genetic studies of family clusters and relatives of affective probands
      have shown a high incidence of affected relatives. A dominant mode of
      inheritance, rather than a recessive one, seems more likely. Multiple genetic
      causes of adult-onset hyperandrogenism and chronic anovulation have been
      identified. Chromosomal studies of patients with PCOS have shown no consistent
      abnormality. Molecular genetic studies are now ongoing. Future genetic models
      should consider such problematic areas as the heterogeneity of the syndrome,
      phenotypes in males as well as in females in the nonreproductive years, the
      exclusion of secondary causes of hyperandrogenism, and the persistence of a
      syndrome that adversely affects fecundity.

PMID- 7825647
TI  - Androgenetic alopecia: an autosomal dominant disorder.
AB  - A hereditary, androgen-driven disorder, androgenetic alopecia is the most common
      form of alopecia in humans: its prevalence is 23-87%. Central alopecia is more
      severe in men; women are more likely to experience diffuse thinning. The acute
      onset of alopecia in those with inflammatory diseases of the scalp suggests a
      variety of etiologies, including the impact of inflammatory cells, release of
      cytokines, presence of growth factors, and increased interaction of stromal
      cells. Therapeutic modalities, which are most effective when used in
      combinations, utilize hair growth promoters, antiandrogens, and androgen blockade
      agents.

PMID- 7825648
TI  - Aging skin.
AB  - Aging of the skin is a composite of actinic damage, chronologic aging, and
      hormonal influences. The majority of changes associated with aging, such as
      wrinkles and solar lentigines ("liver spots"), are due to photoaging and reflect
      cumulative sun exposure as well as skin pigmentation. Classically, chronologic
      aging includes those cutaneous changes that occur in non-sun-exposed areas, such
      as the buttocks, and are observed in both men and women. A clinical example would
      be soft tissue sagging due to elastic fiber degeneration. In women,
      investigations into the effect of hormones on aging of the skin have concentrated
      on estrogens; in men, there have been a limited number of studies on the
      influence of testosterone. The latter have shown an age-dependent decrease in
      tissue androgens in pubic skin, but not scrotal or thigh skin. To date, age has
      not been shown to have an effect on androgen receptor binding, although a
      decrease in foreskin 5 alpha-reductase activity with increasing age has been
      described. In fibroblast cultures from foreskins, there have been conflicting
      results as to whether 5 alpha-reductase activity decreases in an age-dependent
      manner. Some of the skin changes that have been categorized as secondary to
      chronologic aging, such as decreased sebaceous gland activity and decreased hair
      growth, may actually represent a decline in the concentration of tissue androgens
      with increasing age. The influence of androgens on age-related changes in
      keratinocyte and fibroblast function remains speculative.

PMID- 7825649
TI  - Comparisons of risk factors for HIV-1 infection in Jefferson and Mobile County,
      Alabama.
AB  - A study of the Alabama state AIDS database was conducted to determine whether
      differences exist in demographic and risk characteristics between patients with
      HIV-1 in Jefferson and Mobile County. The authors found that the age distribution
      of patients with HIV-1, the percent of those having AIDS, and the percent of
      those surviving were very similar. However, significant differences existed in
      patient-reported risk factors in the two counties. Homosexuality was reported as
      the major risk factor in both counties. However, there was proportionately more
      homosexuality reported in Jefferson County and, conversely, more heterosexuality
      reported in Mobile. There also were significant differences in race and gender
      distributions in the two counties. This was due in part to the proportionately
      higher prevalence of African American females of reproductive age with HIV-1 in
      Mobile County. This may pose a significantly greater risk for pediatric AIDS
      among African American females in Mobile County.

PMID- 7825650
TI  - Diseases of renal adenosine triphosphatase.
AB  - Most renal transport is a primary or secondary result of the action of one of
      three membrane bound ion translocating ATPase pumps. The proximal tubule
      mechanisms for the reabsorption of salt, volume, organic compounds, phosphate,
      and most bicarbonate reabsorption depend upon the generation and maintenance of a
      low intracellular sodium concentration by the basolateral membrane Na-K-ATPase
      pump. The reabsorption of fluid and salt in the loop of Henle is similarly
      dependent on the energy provided by Na-K-ATPase activity. Some proximal tubule
      bicarbonate reabsorption and all distal nephron proton excretion is a product of
      one of two proton translocating ATPase pumps, either an electrogenic H-ATPase or
      an electroneutral H-K-ATPase. In this article, the authors review the
      biochemistry and physiology of pump activity and consider the pathophysiology of
      proximal and distal renal tubular acidosis, the Fanconi syndrome, and Bartter's
      syndrome as disorders of ATPase pump function.

PMID- 7825652
TI  - Human lymphocyte antigens in Graves' disease: correlation with persistent course
      of disease.
AB  - Graves' disease is a thyroid autoimmune disorder associated with specific human
      lymphocyte antigen (HLA) alleles, characterized by an unpredictable long-term
      course. To investigate possible relations between HLA phenotype and outcome of
      the disease, the authors typed for HLA antigens in 105 patients with Graves'
      disease with different course of disease. All patients were treated with
      antithyroid drugs for at least 12 months; 29 patients had stable remission 24 or
      more months after withdrawal of treatment; 76 patients had persistent disease--66
      unremitting/relapsing hyperthyroidism, 10 stable hypothyroidism--36 or more
      months after onset of disease. The following findings emerged from this study: 1)
      HLA B8 and DR3 were increased significantly in Graves' patients versus 6,682
      control subjects from the same geographic area (23.80% vs 12.01%, odds ratio [OR]
      1.98, and 31.43% vs 18.00%, OR 1.75, respectively); the antigen combinations B8
      DR3, B8-Cw7-DR3, and A1-B8-Cw7-DR3 were significantly more frequent in Graves'
      patients vs control subjects; in addition, these combinations were present
      exclusively in patients with persistent disease (B8-DR3 28.95%, OR 7.14, B8-Cw7
      DR3 27.63%, OR 11.24, and A1-B8-Cw7-DR3 18.42%, OR 11.29). These data provide
      evidence that not only susceptibility to Graves' disease, but also persistent
      activity of the autoimmune process, producing either hyperthyroidism or stable
      hypothyroidism, is associated with specific HLA antigen phenotypes.

PMID- 7825651
TI  - Glomerular function and structure in the sodium-replete and sodium-deplete
      uninephrectomized spontaneously hypertensive rat: effect of blood pressure
      reduction, glomerular structure, and blood pressure reduction.
AB  - To assess the effects of chronic dietary sodium restriction and blood pressure
      reduction on glomerular function and structure during the pathogenesis of
      hypertensive renal disease, experiments were conducted in uninephrectomized (UNX)
      spontaneously hypertensive rats (SHR) using the dihydropyridine calcium
      antagonist manidipine. Male SHRs underwent UNX at age 10-11 weeks and
      subsequently were assigned to one of four groups: sodium-replete (0.4%); sodium
      replete and a predetermined antihypertensive dose of manidipine (20 mg/kg body
      weight); sodium-deplete (0.09%); and sodium-deplete and manidipine (20 mg/kg body
      weight). Twelve weeks later, renal morphologic and functional studies were
      performed. Sodium restriction had no significant effect on systolic blood
      pressure, but creatinine clearance and urinary protein excretion were decreased.
      Importantly, mean glomerular volume and the prevalence of mesangial expansion
      were lower with sodium restriction. This occurred in the presence of high
      concentrations of plasma and renal tissue angiotensin II. Manidipine
      significantly reduced systolic blood pressure in the sodium-replete and sodium
      deplete UNX-SHRs. This therapy was not associated with significant changes in
      creatinine clearance and urinary protein excretion in the sodium-deplete or
      sodium-replete UNX-SHRs. The prevalence of mesangial expansion in the sodium
      replete UNX-SHR was approximately 50% lower with manidipine. Plasma and renal
      tissue angiotensin II concentrations were not affected by the drug. In the sodium
      deplete UNX-SHR, the prevalence of mesangial expansion was not reduced further by
      manidipine. However, plasma and renal tissue angiotensin II concentrations were
      increased significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7825653
TI  - Animal model of spinal cord infarction induced by cholesterol embolization.
AB  - Though several animal models of ischemic brain infarction have been developed, no
      animal model of purely ischemic spinal cord infarction exists. In humans, such
      paralysis often occurs as a complication of aortic surgery. While working on an
      animal model of cholesterol embolic renal disease, the authors produced an animal
      model of ischemic spinal paralysis by direct intraaortic injection of cholesterol
      suspension. With histologic examination of spinal cords of the paralyzed rats,
      prominent cholesterol crystals were found obliterating the lumen of the anterior
      and/or posterior spinal arteries. Spinal cord infarction was seen most
      prominently in the lateral columns and anterior horns, though other areas also
      were affected. Permanent paraplegia developed in most rats, but transient
      paralysis developed in a few, followed by partial or full recovery. This model of
      spinal infarction in nonanesthetized rats can be used to study the
      pathophysiology and therapy of spinal infarction.

PMID- 7825654
TI  - Dobutamine effects on systole and diastole in rats with myocardial infarction.
AB  - In this article, the authors attempt to determine the effect of catecholamine
      stimulation on the systolic and diastolic properties of the left ventricle (LV)
      in rats with chronic infarction. Male Sprague-Dawley rats underwent coronary
      artery ligation at 8-10 weeks of age. Baseline hemodynamics were measured 1-2
      months after infarction. Dobutamine was administered in bolus injections of
      increasing concentrations, and peak hemodynamic response after each dose was
      recorded. Rats were divided into three groups: controls (n = 14), rats with
      infarct size less than 30% of LV (n = 13), and rats with infarct size at least
      30% of LV (n = 9). Baseline hemodynamics were similar among the three groups.
      There was no significant difference in the maximal response of LV systolic
      pressure and heart rate between the three groups. Left ventricle +dP/dt increased
      with dobutamine in all three groups, but rats with infarct size of at least 30%
      had a significantly smaller increase above baseline as compared with control
      rats. In contrast, LV -dP/dt increased to a similar degree in all three
      experimental groups with dobutamine. Although hemodynamics can be affected by
      loading conditions in the intact animal, the magnitude of the change in +dP/dt
      with unaltered -dP/dt suggests that there is an impaired inotropic but not
      lusitropic response to catecholamine stimulation in rats with large chronic
      myocardial infarcts. The findings imply a differential effect of beta-agonist
      stimulation on systolic and diastolic properties of the heart.

PMID- 7825655
TI  - Review: pathophysiology of the pleural space.

PMID- 7825656
TI  - Case report: inhalation therapy of paromomycin is effective for respiratory
      infection and hypoxia by cryptosporidium with AIDS.
AB  - A 24-year-old man with AIDS and hemophilia A had intractable diarrhea and fever.
      Upon examination of stool and of a sigmoidal biopsy specimen, cryptosporidium was
      revealed. Approximately 2 months after admission, respiratory infection with
      hypoxia due to cryptosporidium developed. Paromomycin inhalation was effective
      therapy. To the authors' knowledge, this is the first case of respiratory
      cryptosporidiosis treated successfully by paromomycin inhalation.

PMID- 7825658
TI  - Unfamiliar drug uses.

PMID- 7825657
TI  - Case report: congenital adrenal hyperplasia and malignant Leydig cell tumor.
AB  - Leydig cell tumors are very rarely seen testicular tumors and can be difficult to
      distinguish from testicular tumors of the adrenogenital syndrome. Testicular
      tumors of the adrenogenital syndrome are confined to patients with congenital
      adrenal hyperplasia. The authors report a case of a patient with malignant Leydig
      cell tumor and a history of congenital adrenal hyperplasia (adrenogenital
      syndrome). To the authors' knowledge, this has not been reported previously.

PMID- 7825659
TI  - Tell the world what you do.

PMID- 7825660
TI  - Hemodynamic puzzle.

PMID- 7825661
TI  - The good soldier.

PMID- 7825662
TI  - Update your asthma care from hospital to home.

PMID- 7825663
TI  - Talking to physicians about pain control.

PMID- 7825664
TI  - Clinical snapshot: abdominal aortic aneurysm.

PMID- 7825665
TI  - Caring for a patient with an intracoronary stent.

PMID- 7825666
TI  - Emergency! Fast action for subarachnoid hemorrhage.

PMID- 7825667
TI  - The nursing life. An iron fence in Ecuador.

PMID- 7825668
TI  - Enabling behavior: the tender trap.

PMID- 7825669
TI  - Books of the year.

PMID- 7825670
TI  - Alcohol on the physician's breath.

PMID- 7825671
TI  - Common questions about osteoporosis and menopause.

PMID- 7825672
TI  - Health care reform: getting it right this time.

PMID- 7825673
TI  - Nora's world.

PMID- 7825674
TI  - Poor correlation between reactive syphilis serology and human immunodeficiency
      virus testing among potential cornea donors.
AB  - PURPOSE: The current practice in which eye banks screen cornea donors for
      syphilis is based mainly on the potential utility of positive syphilis serology
      as a surrogate marker for human immunodeficiency virus-1 (HIV-1) infection. We
      examined the correlation between positive syphilis and HIV-1 serologies within
      the potential cornea donor population. METHODS: We distributed a questionnaire to
      94 eye banks in the United States regarding their rates of positive serology for
      syphilis and HIV-1 between Feb. 1 and July 30, 1992. We subsequently used the
      polymerase chain reaction for HIV-1 to further evaluate the whole blood of 21
      rapid plasma reagin and fluorescent treponemal antibody-positive, HIV-1 enzyme
      linked immunosorbent assay (ELISA)-negative cornea donors to determine whether
      these donors were infected with HIV-1 but were within a seronegative window for
      HIV-1 antibodies at their time of death. RESULTS: Of 8,932 donors screened, 103
      (1.15%) had reactive screening for syphilis serology and 35 (0.39%) were HIV-1
      seropositive. No donor with positive syphilis serology was also HIV-1
      seropositive. Twelve of 31 donors who originally tested seropositive for syphilis
      by nontreponemal screening tests (Venereal Disease Research Laboratory or rapid
      plasma reagin tests) proved seronegative for syphilis when further tested with a
      treponemal test (FTA-ABS or microhemagglutination-Treponema pallidum), suggesting
      a high (38.7%) false-positive rate for the syphilis screening tests.
      Additionally, all 21 rapid plasma reagin and fluorescent-treponemal antibody
      positive, HIV-1 ELISA-negative donors further tested were also negative for HIV-1
      by the polymerase chain reaction. CONCLUSIONS: Among potential cornea donors, a
      population prescreened for identifiable HIV-1 risk factors, positive syphilis
      serology appears to be a poor marker for HIV-1 infection. The role of syphilis
      screening of potential cornea donors may need to be reevaluated.

PMID- 7825675
TI  - Sarcoidosis of the eyelid skin.
AB  - PURPOSE/METHODS: A 34-year-old woman with a history of pulmonary sarcoidosis was
      referred for examination and treatment of suspected molluscum contagiosum nodules
      of the eyelids. After full ophthalmic examination, she underwent a biopsy of an
      eyelid nodule. RESULTS/CONCLUSIONS: Histopathologic examination of the eyelid
      nodule showed numerous, noncaseating granulomas as well as giant cells. This case
      represents the rare findings of sarcoidosis of the eyelid skin in a patient with
      chronic but not ocular sarcoidosis.

PMID- 7825676
TI  - Fractionated epibulbar I-125 plaque radiotherapy for recurrent mucoepidermoid
      carcinoma of the bulbar conjunctiva.
AB  - PURPOSE/METHODS: A patient with recurrent conjunctival mucoepidermoid carcinoma
      was treated successfully with surgical excision of the tumor and fractionated
      epibulbar I-125 plaque radiotherapy. RESULTS/CONCLUSIONS: Local excision with
      fractionated epibulbar plaque radiotherapy is an effective means of eradication
      in select cases of recurrent mucoepidermoid carcinomas of the conjunctiva. This
      treatment may avoid more aggressive surgical treatment and preserve vision.

PMID- 7825677
TI  - Open-angle glaucoma after pars plicata lensectomy and vitrectomy for congenital
      cataracts.
AB  - PURPOSE/METHODS: We examined an infant with familial cataracts in whom bilateral
      open-angle glaucoma developed shortly after pars plicata lensectomy with anterior
      vitrectomy. RESULTS/CONCLUSIONS: Some eyes with congenital nuclear cataracts have
      a predisposition to develop glaucoma after removal of the cataract, which is
      irrespective of the method chosen to remove the cataract. Careful monitoring of
      the intraocular pressure is indicated.

PMID- 7825678
TI  - Human T-cell lymphotropic virus type I-associated uveitis in an African American.
AB  - PURPOSE/METHODS: In an African American woman with the human T-cell lymphotropic
      virus type I associated with uveitis, clinical and ocular findings were
      correlated with detection of viral genome by polymerase chain reaction, and by
      viral antigen detection in cultured peripheral blood mononuclear cells.
      RESULTS/CONCLUSIONS: High levels of human T-cell lymphotropic virus type I gene
      expression in multiple samples over a two-year period strongly support the
      diagnosis of human T-cell lymphotropic virus type I uveitis. Systemic
      corticosteroid therapy resulted in partial remission.

PMID- 7825679
TI  - Acute posterior ophthalmomyiasis interna treated with photocoagulation.
AB  - PURPOSE/METHODS: We studied a patient with subretinal myiasis with pain and
      rapidly progressive visual loss and found that prompt photocoagulation resulted
      in marked visual improvement. A 16-year-old boy had subconjunctival hemorrhage
      and periocular pain associated with progressive visual loss of 6/200 over a four
      day period. RESULTS/CONCLUSIONS: A live maggot found crawling in the subretinal
      space was promptly photocoagulated with an argon green laser. Within one month,
      the visual acuity improved to 20/50. Laser treatment of a subretinal larva does
      not generally induce marked inflammation and often results in good visual
      recovery.

PMID- 7825680
TI  - Endogenous Aspergillus endophthalmitis after lung transplantation.
AB  - PURPOSE/METHODS: By fundus photography and histopathologic examination, we
      documented a case of early endogenous Aspergillus endophthalmitis in a 29-year
      old man after lung transplantation. RESULTS/CONCLUSIONS: The clinical and
      histopathologic features of this case are consistent with those of previous case
      reports of endogenous Aspergillus endophthalmitis. Endogenous Aspergillus
      endophthalmitis represents a manifestation of disseminated aspergillosis, usually
      a fatal infection. This diagnosis should be considered in immunocompromised
      patients with visual disturbances, as early recognition of the fundus appearance
      may aid in systemic treatment.

PMID- 7825681
TI  - Central retinal vein occlusion in a patient with anorexia nervosa.
AB  - PURPOSE/METHODS: We evaluated a unilateral retinal vascular abnormality in a 21
      year-old woman with anorexia nervosa. RESULTS/CONCLUSION: The patient had weight
      loss, amenorrhea, and anemia. The left eye had a nonischemic central retinal vein
      occlusion and a visual acuity of 20/200. With treatment, the retinal hemorrhages
      disappeared and visual acuity in the left eye improved to 20/20. Central retinal
      vein occlusion may be a rare complication of anorexia nervosa.

PMID- 7825682
TI  - Lateral geniculate nucleus in glaucoma.

PMID- 7825683
TI  - Studies of the blood-aqueous barrier in diabetes mellitus.

PMID- 7825684
TI  - Screening for ocular toxicity in asymptomatic patients treated with tamoxifen.

PMID- 7825685
TI  - Corneal lipidosis in patients with the acquired immunodeficiency syndrome.
AB  - PURPOSE: Certain drugs bind to anionic phospholipids of lysosomal membranes and
      produce progressive intracellular accumulation of lamellar inclusions. We studied
      two patients treated for opportunistic infections associated with the acquired
      immunodeficiency syndrome (AIDS), who developed bilateral ocular surface changes
      suggestive of drug-induced corneal lipidosis. METHODS: Two patients with AIDS had
      translucent vacuoles within the corneal epithelium and mild conjunctival
      hyperemia. Because the differential diagnosis included microsporidial
      keratoconjunctivitis, biopsies of the ocular surface were performed for
      histopathologic analysis. RESULTS: Transmission electron microscopy of corneal
      epithelial debridement and conjunctival biopsy specimens showed intracellular,
      electron-dense lipoidal bodies and multilaminated lysosomal inclusions suggestive
      of a drug-induced lipidosis. Both patients also had tubuloreticular inclusions in
      conjunctival capillary endothelial cells. The ocular surface changes resolved
      within one to three months after dosage reduction or discontinuation of systemic
      ganciclovir and acyclovir. CONCLUSIONS: Drug-induced phospholipidosis is a cause
      of punctate corneal epitheliopathy during AIDS, but the responsible agent remains
      to be identified.

PMID- 7825686
TI  - Combined phacoemulsification, posterior chamber intraocular lens implantation,
      and trabeculectomy with mitomycin C.
AB  - PURPOSE: We evaluated the effectiveness of combined phacoemulsification,
      posterior chamber intraocular lens implantation, and trabeculectomy with
      mitomycin C in patients with coexisting cataract and glaucoma. METHODS: We
      conducted a retrospective review of the records of 21 consecutive patients who
      had combined phacoemulsification, posterior chamber intraocular lens
      implantation, and trabeculectomy with mitomycin C. Patients were selected for the
      combined procedure on the basis of the degree to which intraocular pressure was
      controlled, toleration of medical therapy, degree of glaucomatous optic nerve
      damage, and extent of visual impairment because of cataract. Nine (43%) of the 21
      patients had previous incisional surgery and were at high risk of surgical
      failure. All patients had at least six months' follow-up. Sixteen (76%) of 21
      patients had at least one year of follow-up. RESULTS: The mean preoperative
      intraocular pressure was 20.8 +/- 5.0 mm Hg (range, 13 to 35 mm Hg), which
      decreased to a mean postoperative intraocular pressure of 15.1 +/- 3.1 mm Hg
      (range, 9 to 21 mm Hg) as measured at last follow-up (P = .0002). The intraocular
      pressure was controlled between 6 and 21 mm Hg) in all patients at last follow
      up. Seventeen (81%) of 21 patients had a best-corrected visual acuity of 20/40 or
      better at last follow-up. No patient had a decrease in visual acuity after
      surgery. Fifteen (71%) of 21 patients were using no antiglaucoma medications at
      last follow-up. Four of the remaining six patients were using one medication, and
      two were using two medications. A hyphema (less than 1.0 mm) was seen in seven
      (33%) of 21 patients and was the most common postoperative complication. No
      patient had a postoperative wound or bleb leak or a shallow anterior chamber. No
      patient developed symptomatic hypotony. CONCLUSIONS: The glaucoma triple
      procedure with adjunctive mitomycin C appears to be a safe and effective surgical
      technique for treating selected patients with coexisting cataract and glaucoma.

PMID- 7825687
TI  - Adjunctive mitomycin C in primary trabeculectomy in phakic eyes.
AB  - PURPOSE: The addition of antiproliferative agents, most recently mitomycin C, has
      improved the outcome of glaucoma filtering surgery in eyes with a high risk of
      surgical failure. We conducted the present study to determine whether adjunctive
      mitomycin C would increase the success rate of primary trabeculectomies in phakic
      eyes. METHODS: Thirty-three eyes of 33 consecutive patients with phakic primary
      open-angle glaucoma, who were predominantly black (24 black and nine white), who
      underwent primary trabeculectomy with adjunctive subconjunctival mitomycin C (0.5
      mg/ml for three minutes) were compared with a demographically similar historical
      control group of 30 eyes of 30 consecutive patients (20 black and ten white) with
      phakic primary open-angle glaucoma, who had undergone primary trabeculectomy
      without an adjunctive antifibrotic agent. RESULTS: Although the mean preoperative
      intraocular pressures were similar in both groups (29.0 +/- 6.4 mm Hg in the
      mitomycin C group and 29.5 +/- 10.0 mm Hg in the control group, P = .61), the
      mean postoperative intraocular pressure at each follow-up period was
      significantly lower in the mitomycin C group than in the control group (10.3 +/-
      7.1 vs 14.5 +/- 5.1 mm Hg at six months, P = .02; 10.5 +/- 4.9 vs 14.5 +/- 4.4 mm
      Hg at 12 months, P = .01; and 10.0 +/- 3.1 vs 17.2 +/- 3.0 mm Hg at 18 months, P
      = .004, respectively). The mean number of postoperative medications was also
      significantly lower in the mitomycin C group (0.2 +/- 0.4 vs 1.1 +/- 1.4
      medications at six months, P = .007; 0.3 +/- 0.4 vs 0.9 +/- 1.1 medications at 12
      months, P = .04; and 0.3 +/- 0.5 vs 1.7 +/- 1.2 medications at 18 months, P =
      .01, respectively). However, the mitomycin C group had a significantly higher
      incidence of prolonged hypotony (intraocular pressure less than 6 mm Hg) compared
      with the control group (15% vs 0% at nine months, P = .05). Younger age was
      associated with a higher incidence of persistent hypotony. CONCLUSIONS:
      Adjunctive subconjunctival mitomycin C (0.5 mg/ml for a three-minute exposure) in
      primary trabeculectomies of phakic eyes, while increasing the success rate by
      decreasing intraocular pressure and postoperative medications, is associated with
      a higher incidence of prolonged hypotony.

PMID- 7825688
TI  - Excimer laser filtration surgery.
AB  - PURPOSE: In order to remove precisely scleral tissue overlying Schlemm's canal
      with minimal trauma as an outpatient procedure under local anesthetic, we used a
      VisX Twenty/Twenty excimer laser. METHODS: We performed excimer laser filtration
      in three enucleated pig eyes, seven enucleated human eyes, and seven eyes of
      seven patients with severe glaucoma. Precise ablation to Schlemm's canal was
      confirmed by scanning electron microscopy in the enucleated eyes. For the
      patients, a local anesthetic was used, and a custom-made holder was used to
      mobilize the conjunctiva and fix the eye. RESULTS: A functional sclerostomy was
      obtained with 1,780 to 5,965 pulses, using a 2 x 1-mm slit. In our mean follow-up
      of nine months (range, six to 12 months) the excimer laser filtration technique
      achieved controlled filtration in five of seven patients and minimized
      conjunctival trauma. One patient subsequently underwent cataract extraction.
      CONCLUSIONS: This study indicates that excimer laser filtration is an effective
      technique for achieving filtration in glaucoma. It may reduce the complications
      of glaucoma filtration surgery, particularly the incidence of shallow anterior
      chamber postoperatively, as it leaves the trabecular meshwork intact.

PMID- 7825689
TI  - Progression of nuclear sclerosis and long-term visual results of vitrectomy with
      transforming growth factor beta-2 for macular holes.
AB  - PURPOSE: We studied the progression of cataracts and visual acuity up to 36
      months after vitrectomy and instillation of transforming growth factor beta-2 for
      treatment of full-thickness macular holes. METHODS: Sixty-four eyes with
      idiopathic and two with traumatic macular holes in this prospective consecutive
      series were divided into the following two groups: 56 phakic eyes were treated
      with 70, 330, or 1,330 ng of transforming growth factor beta-2 to study the
      progression of cataracts, and 31 phakic or pseudophakic eyes were treated with
      1,330 ng of transforming growth factor beta-2 to study the long-term visual
      acuity after macular hole surgery. RESULTS: Eyes in the cataract progression
      study had a mean preoperative nuclear sclerosis grade of 0.4, which increased to
      2.4 on final lens examination at a mean of 12.4 months postoperatively. The
      amount of nuclear sclerosis increased progressively with duration of follow-up,
      and 16 (76%) of 21 eyes followed up for 24 months or more required cataract
      extraction. The mean preoperative posterior subcapsular cataract grade was 0.0
      and increased only slightly to 0.25 on final lens examination. All eyes had
      initial successful closure of the macular hole, but the macular hole reopened in
      two eyes (between six and 12 months and at 19 months) for an overall success rate
      of 29 (93.5%) of 31 eyes at a mean of 19.5 months. The visual acuity increased
      two or more Snellen lines in 29 (93.5%) of 31 eyes. The final visual acuity was
      20/40 or better in 23 (74%) of 31 eyes and the visual improvement was stable in
      eyes followed up for three years. CONCLUSIONS: Nuclear sclerotic cataracts
      progress substantially after macular hole surgery with a long-acting intraocular
      gas tamponade. The visual acuity often decreases 12 or more months after
      vitrectomy because of cataract progression, but the visual results of vitrectomy
      and transforming growth factor beta-2 for macular holes are excellent when the
      cataracts are removed.

PMID- 7825690
TI  - Course of vitreomacular traction syndrome.
AB  - PURPOSE: Although the course of vitreomacular traction syndrome is necessary to
      treat patients or to establish the value of the surgical technique, little
      information is available about its course. In this study, we ascertained the
      natural history of vitreomacular traction syndrome. METHODS: We retrospectively
      studied 53 consecutive symptomatic eyes with vitreomacular traction syndrome.
      RESULTS: In 43 (81%) of 53 eyes with cystoid macular changes at the diagnostic
      examination, 29 (67%) of 43 had cystoid changes that persisted during the median
      follow-up period of 60 months. The visual acuities at the time of the final
      examination decreased two Snellen lines or more from the initial measurement in
      34 (64%) of 53 eyes. During the follow-up period, six (11%) of 53 eyes developed
      complete posterior vitreous detachment. The number of eyes with resolved cystoid
      changes or stable visual acuity was significantly higher when complete
      vitreomacular separation occurred (six of six) than when it did not (three [8%]
      of 37, P = .01; 13 [28%] of 47, P = .01). CONCLUSIONS: Most symptomatic eyes with
      vitreomacular traction syndrome underwent a further decrease in visual acuity.
      Complete vitreomacular separation, which occurs infrequently in eyes with the
      disorder, allows resolution of cystoid changes and improvement of visual acuity.

PMID- 7825691
TI  - Evaluation of vitrectomy machines as a source of false-positive culture
      contamination in endophthalmitis.
AB  - PURPOSE: We sought to determine whether a venturi-aspiration vitrectomy machine
      could contaminate a vitrectomy culture. METHODS: Ninety vitrectomies were
      simulated in a hospital operating room and were cultured with standard
      techniques. An additional 90 control specimens were cultured in the exact same
      manner, but the vitrectomy machine was not used. Instead, the control specimens
      were placed directly into a sterile vitrectomy cassette. Contamination rates in
      the two groups were compared. RESULTS: Contamination occurred in four of 90
      vitrectomy-simulation cultures and in three of 90 control cultures. This
      difference in contamination rate was not statistically significant. CONCLUSIONS:
      Although the result of a culture of the vitrectomy effluent can be false
      positive, the source of contamination is not likely to be the vitrectomy machine.

PMID- 7825692
TI  - Retinitis pigmentosa associated with a dominant mutation in codon 46 of the
      peripherin/RDS gene (arginine-46-stop).
AB  - PURPOSE: We identified genetic mutations and characterized their associated
      phenotypes in patients with retinitis pigmentosa. METHODS: Patients with
      retinitis pigmentosa were prospectively examined and screened for genetic
      mutations. RESULTS: A 46-year-old man with retinitis pigmentosa was found to have
      a heterozygous mutation in the peripherin/RDS gene (arginine-46-stop). He had
      late onset of symptoms and demarcated peripheral retinal atrophy. All five first
      degree relatives including his parents had no detectable mutations or retinitis
      pigmentosa. Genotypic data were consistent with reported family structure.
      CONCLUSIONS: This study shows that new dominant mutations are a rare cause of
      isolated, or simplex, cases of retinitis pigmentosa. Identification of these
      mutations is helpful for genetic counseling.

PMID- 7825693
TI  - Screening corneas for human immunodeficiency virus type 1 proviral DNA by
      polymerase chain reaction.
AB  - PURPOSE: We evaluated the sensitivity of the polymerase chain reaction as a
      technique to directly screen potential donor corneas for human immunodeficiency
      virus type 1 (HIV-1) proviral DNA. METHODS: DNA from the central 8.0-mm cornea,
      limbal cornea, aqueous humor, and retina from 22 eyes of 11 cadavers seropositive
      for HIV was extracted and amplified by polymerase chain reaction using primers
      specific for the gag and env regions of the HIV-1 genome. The identity of
      amplification products was confirmed by Southern blot hybridization. RESULTS:
      Viral DNA was detected in four (18.2%) of 22 central corneas, one (4.5%) of 22
      limbal corneas, one (6.3%) of 16 aqueous humor samples, and seven (31.8%) of 22
      retinas. No correlation was noted between the presence of HIV-1 proviral DNA in
      samples from the central cornea and from the other tissues tested from the same
      eye. CONCLUSIONS: Within the limits of our assay, processing and analysis of
      limbal cornea, aqueous humor, and retina by polymerase chain reaction may not
      reliably ascertain the presence of HIV-1 in the central, transplantable cornea.

PMID- 7825694
TI  - Macular sparing as a perimetric artifact.
AB  - PURPOSE: We studied the hypothesis that the typical macular sparing of a few
      degrees was based on an unstable fixation coupled with a nystagmiform searching
      movement in the direction of the seeing hemiretina. METHODS: By means of
      microperimetry with a scanning laser ophthalmoscope, we recently tested the
      visual fields of 15 hemianoptic patients, through direct visual control of the
      retina. The tests provided us with accurate information about all fixation shifts
      that occurred. RESULTS: Twelve patients showed macular sparing of 1 to 5 degrees
      both in the Goldmann visual field and in the scanning laser ophthalmoscope field.
      Their fixation shifted regularly 1 to 10 degrees toward the seeing hemiretina one
      to two times per second, then returned rapidly to the foveola. Conversely, three
      patients showed greater macular sparing, and they all had particular
      characteristics--extensive fixation shifts, dual fixation, and limited
      quadrantanopsia. CONCLUSIONS: We believe that macular sparing could be
      interpreted as a perimetric (not an anatomic) artifact, provided that the results
      of these tests on 15 patients are confirmed by further similar studies.

PMID- 7825695
TI  - Measurement of the subarachnoid pressure of the optic nerve in human subjects.
AB  - PURPOSE: We measured the subarachnoid pressure of the optic nerve in 16 patients
      scheduled for ocular enucleation or evisceration. METHODS: We measured the
      subarachnoid pressure of the optic nerve directly with an electronic digital
      manometer in 16 patients scheduled for enucleation or evisceration for various
      blinding conditions. The nerve was exposed via a medial orbitotomy, and the
      subarachnoid pressure of the optic nerve was measured 5 mm posterior to the optic
      nerve head. The subarachnoid pressure of the optic nerve was also measured in
      five patients who were placed in the Trendelenburg position (head declined at a
      30-degree angle) for three minutes. RESULTS: The subarachnoid pressure of the
      optic nerve varied from 4 to 14 mm Hg in the 16 patients tested. The mean
      subarachnoid pressure of the optic nerve was 8.5 mm Hg in the 16 patients tested.
      An increase of 1 to 2 mm Hg in the subarachnoid pressure was observed in all five
      patients placed in the Trendelenburg position. CONCLUSIONS: Subarachnoid pressure
      of the optic nerve can be measured in vivo in humans. The values obtained are
      consistent with the known physiologic range of intracranial pressure. There was
      no statistically significant correlation between subarachnoid pressure of the
      optic nerve and age or cause of blindness. The subarachnoid pressure of the optic
      nerve varies over a wide range.

PMID- 7825696
TI  - Ophthalmic manifestations of Rathke's cleft cysts.
AB  - PURPOSE: We studied the neuro-ophthalmic features of patients with symptomatic
      Rathke's cleft cysts, to distinguish features of Rathke's cleft cysts from those
      of craniopharyngioma. METHODS: Eleven patients who had undergone surgery for
      symptomatic Rathke's cleft cysts in the Liverpool University Department of
      Neurological Science were identified from the records. Histopathologic analyses,
      clinical notes, and radiologic investigations were reviewed. RESULTS: Eight of
      the 11 patients initially had visual problems. Reduced visual acuity, visual
      field defect, or both, were detected in nine patients. Optic atrophy was observed
      in eight patients. Other initial features included headaches, epilepsy, and
      endocrine disturbance. All patients recovered from surgery, and an improvement in
      the visual acuity or visual field defect was noted in six patients. CONCLUSIONS:
      Symptomatic Rathke's cleft cysts often manifest as visual disturbance. Every
      effort to distinguish Rathke's cleft cysts from craniopharyngiomas should be made
      preoperatively. Rathke's cleft cysts only require limited surgical intervention,
      and radiotherapy is not necessary. Early recognition and treatment can lead to
      improvement in visual function.

PMID- 7825697
TI  - Syphilis, serologic testing, and the setting of standards for eye banks.

PMID- 7825698
TI  - A minor modification of the Hughes' operation for lower eyelid reconstruction.
AB  - PURPOSE/METHODS: We modified the Hughes' technique to decrease the frequency of
      persistent conjunctival hyperemia on the reconstructed lower eyelid margin.
      RESULTS/CONCLUSION: When the conjunctival flap is divided at the second stage of
      the operation, the tissue is trimmed flush with the reconstructed lower eyelid
      margin rather than advancing the flap over the eyelid margin. This minor
      modification has yielded satisfactory functional and aesthetic results in 70
      patients.

PMID- 7825699
TI  - Combined dacryops with underlying benign mixed cell tumor of the lacrimal gland.
AB  - PURPOSE/METHODS: Computed tomographic scan disclosed a well-defined mass in the
      right lacrimal fossa of a 57-year-old woman. We excised and examined the mass.
      RESULTS/CONCLUSIONS: The mass was a combination of a small benign mixed cell
      tumor and a large ductal cyst of the lacrimal gland. It is possible that a cyst
      in the lacrimal duct may mask an underlying neoplasm of the lacrimal gland.

PMID- 7825700
TI  - Lacrimal gland hemangiopericytoma.
AB  - PURPOSE/METHODS: A 49-year-old woman with a left orbital mass was referred to an
      orbital clinic. Clinical investigation suggested a lacrimal gland lesion and the
      patient underwent lateral orbitotomy and excisional biopsy for a suspected
      pleomorphic adenoma in the lacrimal gland. RESULTS/CONCLUSION: Histopathologic
      evaluation disclosed a hemangiopericytoma originating within the lacrimal gland.
      Although hemangiopericytoma does not usually occur in this location, it may be
      added to the differential diagnosis of lacrimal gland enlargement.

PMID- 7825701
TI  - Accepting the challenge of outcome research: examining the effectiveness of
      occupational therapy practice.

PMID- 7825702
TI  - The effects of different treatment activities on functional fine motor
      coordination in adults with brain injury.
AB  - OBJECTIVES: Occupational therapists frequently work to improve the fine motor
      coordination skills of adults who have dexterity deficits secondary to brain
      injury. Most therapists use a combination of tabletop and functional activities
      to foster improved coordination in these clients. This study examined the effects
      of puzzle construction and kitchen activities on fine motor coordination in a
      group of 45 men with brain injury, as measured by pretest and posttest
      performance on two subtests of the Jebsen-Taylor Test of Hand Function. METHOD:
      Subjects were randomly assigned to either a parquetry block assembly group (n =
      22) or a meal preparation group (n = 23). RESULTS: Subjects in the functional
      meal preparation group showed significantly greater improvement in dominant-band
      dexterity for picking up small objects than subjects in the tabletop puzzle
      activity group. Other coordination test results were comparable for the two
      treatment groups. CONCLUSION: These findings suggest that functional activities
      may be better than tabletop activities for fine motor coordination training with
      this population.

PMID- 7825703
TI  - The effect of music on repetitive disruptive vocalizations of persons with
      dementia.
AB  - OBJECTIVE: This study examined the effect of classical music and favorite music
      on the repetitive disruptive vocalizations of long-term-care facility (LTCF)
      residents with dementia of the Alzheimer's type (DAT). METHOD: Three subjects
      diagnosed with DAT who had a history of repetitive disruptive vocalizations were
      selected for the study. Three single-subject withdrawal designs (ABA, ACA, and
      ABCA) were used to assess subjects' repetitive disruptive vocalizations during
      each phase: no intervention (A); relaxing, classical music (B); and favorite
      music (C). RESULTS: Classical music and favorite music significantly decreased
      the number of vocalizations in two of the three subjects (p < .05). CONCLUSION:
      These findings support a method that was effective in decreasing the disruptive
      vocalization pattern common in those with DAT in the least restrictive manner, as
      mandated by the Omnibus Budget Reconciliation Act of 1987.

PMID- 7825704
TI  - Reinjury prevention follow-through for clients with cumulative trauma disorders.
AB  - OBJECTIVES: Fifteen subjects with upper extremity work-related cumulative trauma
      disorders were involved in a quality improvement study to determine their self
      reported degree of follow-through with reinjury prevention regimens. The effect
      of cuing was also studied. METHOD: During occupational therapy, subjects were
      involved in an educational session that focused on recommendations in ergonomic
      equipment, therapeutic maintenance techniques, body mechanics, and work
      simplification techniques. Follow-through with reinjury prevention education was
      evaluated and rated via telephone interviews approximately 2 weeks (T1) and 4
      weeks (T2) after the educational session. Subjects did not know the questions
      they would be asked at T1, but were cued that their progress would be checked
      again at T2. Dependent t tests were conducted to compare the mean number of
      recommendations for which complete follow-through was expected with the mean
      number of recommendations at T1 and T2 that were implemented completely. RESULTS:
      A significantly lower degree was found of absolute completion of recommendations
      at T1 and T2 than had been anticipated (p < .002). No significant difference
      between T1 and T2 was found, indicating that cuing at T1 had little effect on
      subjects' actual follow-through rate. CONCLUSION: The implications of these
      findings for occupational therapists support the need for further research in
      reinjury prevention and employer education.

PMID- 7825705
TI  - Change in wheelchair transfer performance during rehabilitation of men with
      cerebrovascular accident.
AB  - OBJECTIVES: A retrospective study was conducted to investigate differences in the
      functional outcome between patients with left cerebrovascular accident (left CVA)
      and right cerebrovascular accident (right CVA) in wheelchair transfer
      performance. It was hypothesized that the level of improvement in left CVA and
      right CVA groups of patients would not be the same, due to the different
      constellation of neurological impairments. METHOD: Data were obtained from the
      admission and discharge scores on the Functional Independence Measure of 100 male
      patients, 50 with left CVA and 50 with right CVA. RESULTS: Both groups
      demonstrated a statistically significant improvement between admission and
      discharge for wheelchair to bed, wheelchair to toilet, and wheelchair to tub or
      shower transfers (p < .001). However, there were no statistically significant
      differences between the two groups at admission or discharge for any of the three
      transfers, even after statistical removal of the effects of age, number of days
      from onset of stroke to rehabilitation, and number of days in rehabilitation.
      CONCLUSION: The lack of difference between the groups at time of discharge may
      have obscured a difference in the rate of transfer learning during the course of
      rehabilitation.

PMID- 7825706
TI  - Cerebrovascular accident: relationship of demographic, diagnostic, and
      occupational therapy antecedents to rehabilitation outcomes.
AB  - OBJECTIVE: This study was conducted to identify factors that were significant in
      predicting occupational therapy treatment choices and discharge outcomes after
      inpatient rehabilitation for 112 patients who had experienced a cerebrovascular
      accident. METHOD: A retrospective descriptive study was conducted. RESULTS:
      According to discriminant function analysis, the cerebrovascular accident
      disability score (i.e., level of functional disability) during the initial
      evaluation period was the predictor of discharge outcomes with the most clinical
      significance. A greater proportion of occupational therapy assessment units was
      the most influential occupational therapy factor associated with a positive
      discharge outcome. In one inpatient rehabilitation setting, a greater proportion
      of occupational therapy intervention for all study subjects was directed at the
      level of impairment compared to the level of disability. CONCLUSION: Shorter
      inpatient stays, as well as shifts to outpatient rehabilitation, may require
      occupational therapists to examine whether intervention at the level of
      impairment or disability yields the best functional outcomes for patients who
      have sustained a cerebrovascular accident.

PMID- 7825708
TI  - Vestibular rehabilitation improves daily life function.
AB  - This article reviews recent research that addresses the functional outcomes of
      intervention for vestibular disorders. Vestibular impairments cause
      disequilibrium, blurred vision, disorientation, and vertigo. These sensory
      disturbances and motor impairments in turn cause dysfunction in many activities
      of daily living and in social interactions that traditional medical treatments do
      not address. The motor sequelae of some vestibular disorders can be treated
      successfully with programs of graded exercises and activities, the functional
      implications of which are described herein. The functional impairments caused by
      other vestibular disorders, which cannot be treated with graded activities, are
      also described. These disorders include bilateral vestibular loss caused by
      connective tissue disorders or by the use of ototoxic medications, tumors of the
      labyrinth or vestibular nerve, and Meniere's disease. Occupational therapy
      intervention for these conditions may involve providing adaptive equipment,
      teaching alternative strategies for performing activities of daily living, and
      psychological intervention for depression and anxiety.

PMID- 7825707
TI  - Stability and change in functional assessment of patients with geropsychiatric
      disorders.
AB  - OBJECTIVES: Functional assessments of patients with geropsychiatric disorders
      accomplished by self-rating, informant rating, and performance test were
      compared. METHOD: Fifty-eight inpatients with major depression or progressive
      dementia were evaluated on three occasions over 6 months with informant and
      patient versions of the Activities of Daily Living Scale of the Older Americans
      Resources and Services Multidimensional Functional Assessment (OARS-ADL) and with
      the Performance Assessment of Self-Care Skills (PASS). RESULTS: Patients' scores
      became significantly worse (p < .01) on the informant version of the OARS-ADL and
      the PASS. Self-ratings with the OARS-ADL did not worsen significantly (p > .05).
      CONCLUSION: Agreement between informant rating and performance test concerning
      functional status of patients with dementia was good. Elderly patients with
      depression may experience subtle deterioration that only becomes apparent on
      performance tests.

PMID- 7825709
TI  - A prediction model of performance in level II fieldwork in physical disabilities.
AB  - OBJECTIVES: A prediction model of performance in physical disabilities fieldwork
      was generated with grades received in the occupational therapy curriculum and in
      prerequisite courses. METHOD: Grades included those from functional anatomy,
      neuroanatomy, physical disabilities lecture, physical disabilities clinic, and
      prerequisite anatomy and physiology courses. Sampling was done collectively over
      graduated occupational therapy classes from 1987 to 1992 at the University of
      Puget Sound. A multiple regression analysis was performed and prediction
      equations were generated for each subscale of the Fieldwork Evaluation for the
      Occupational Therapist. Equations for combinations of the subscale categories
      were also produced. RESULTS: Adjusted R2 values were found to be less than 10% in
      all equations. CONCLUSION: This poor ability of grades to predict fieldwork
      performance suggests that future investigation be focused on variables other than
      grades. Such variables might include student motivation, rapport between the
      student and fieldwork supervisor, and hospital experience in physical
      disabilities.

PMID- 7825710
TI  - Comparison of three myoelectrically controlled prehensors and the voluntary
      opening split hook.

PMID- 7825711
TI  - Documenting functional outcomes.

PMID- 7825712
TI  - Should occupational therapy choose a single functional outcome measure?

PMID- 7825713
TI  - Treat parents of a child with special needs as members of team.

PMID- 7825714
TI  - Skin tests for epidemiologic studies.

PMID- 7825715
TI  - Clustering of allergenic pollen on the basis of skin responses of atopic patients
      by matrix analysis.
AB  - The responses of 148 atopic patients to some 43 different extracts of allergenic
      pollen were tested by prick tests. The measure of dissimilarity was introduced
      and calculated for all pairs of allergens. The investigated allergens were
      clustered into groups, according to their unbiased greatest similarity, by a
      matrix-structuring method. Results indicate that subgroups of allergens can be
      distinguished even within groups of closely related pollen allergens that were
      believed to be fully cross-reactive. A few cases are demonstrated for various
      varieties of olives, pecans, date palms, and turf grasses and for some wild
      chenopods and amaranths. The usefulness of the suggested solution for allergy
      research and for clinical practice is discussed.

PMID- 7825716
TI  - Cat (Fel d I), dog (Can f I), and cockroach allergens in homes of asthmatic
      children from three climatic zones in Sweden.
AB  - We have investigated the levels of cat (Fel d I), dog (Can f I), and cockroach
      (Per a I) allergens in dust from bedrooms, living rooms, kitchens, and bathrooms
      from 123 homes of asthmatic children in three zones of Sweden with varying
      climates. Absolute indoor humidity (AIH), relative humidity (RH), rate of
      ventilation in air changes per hour (ach), and number of airborne particles were
      also measured. Fel d I, Can f I, and Per a I allergen contents were determined by
      mab ELISA, and the levels were related to various environmental factors. The
      major cat allergen, Fel d I, was detected in all homes, and the concentrations
      varied between 16 ng and 28,000 ng/g fine dust. The dog allergen, Can f I, was
      detected in 85% of the homes, and the levels varied from 60 ng to 866,000 ng/g
      dust. Cockroach allergen was detected in only one home (40 ng/g). Fel d I and Can
      f I allergens were equally distributed geographically. Dust from living rooms
      contained significantly higher (P < 0.05) concentrations of both Fel d I and Can
      f I allergens than dust from bedrooms, kitchens, and bathrooms. The levels tended
      to be higher in homes with poor ventilation (< 0.5 ach) and in homes with wall-to
      wall carpets. Significantly higher (P < 0.01) numbers of airborne particles were
      found in homes with high humidity (i.e., AIH > or = 7 g/kg or RH > or =
      45%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7825717
TI  - Anaphylactic reactions to sunflower seed.
AB  - We report on four patients sensitized to sunflower seed. Three of them developed
      anaphylaxis and one chronic bronchial asthma. All four patients reacted the first
      time sunflower seeds were ingested, and all had kept cage birds fed on sunflower
      seeds. Therefore, the route of sensitization was probably by inhalation of
      airborne sunflower seed allergens. Investigation of this type of hypersensitivity
      in 84 atopic patients showed that only three patients were RAST-positive,
      indicating that this allergy is fairly uncommon. On the other hand, when atopic
      persons are exposed to cage birds, the rate of sensitization is rather high, as
      indicated by the fact that in this category 79% were skin prick positive and 21%
      were unequivocably RAST positive to sunflower seed.

PMID- 7825718
TI  - Expression of sCD23 in atopic and nonatopic blood donors: correlation with age,
      total serum IgE, and allergic symptoms.
AB  - Although structure, biologic activities, and expression of the low-affinity IgE
      receptor (FceRII, CD23) have been investigated, the diagnostic value for
      allergies of this molecule and its soluble circulating fragment (sCD23) remains
      unclear. Therefore, serum sCD23 levels were measured in 203 blood donors. They
      were divided into atopic and nonatopic subjects by allergy history, physical
      findings of allergic symptoms, and corresponding specific circulating IgE
      antibodies. The group consisting of nonatopic subjects was divided into four age
      categories in order to exclude age-dependent variations in the expression of the
      low-affinity IgE receptor. In our study population, sCD23 serum levels were not
      influenced by age. Furthermore, no significant differences, especially no
      decrease in serum sCD23 levels, between the four nonatopic age groups were
      detected. There was no significant increase of sCD23 serum levels in atopic
      subjects in comparison with nonatopic blood donors. In addition, no correlation
      between total IgE levels and sCD23 serum levels could be detected, in either the
      group of atopic donors or the group of nonatopics. Our data suggest that the
      circulating low-affinity IgE receptor does not appear to be an additional general
      marker for the diagnosis of allergies, as previously suggested.

PMID- 7825719
TI  - Influence of skin prick test criteria on estimation of prevalence and incidence
      of allergic sensitization in children.
AB  - In a prospective cohort study on atopy in childhood, three skin prick tests (SPT)
      were performed in 1135 primary schoolchildren over a 2-year period. We studied
      the development of average sizes of allergen wheals in reactive children and of
      average sizes of histamine wheals in all children, and we investigated the
      influence of choice of SPT criterion on the prevalence and incidence of
      sensitization. A year-to-year increase of average allergen wheal sizes as well as
      of average histamine wheal sizes was observed. These increases seemed to be
      related to the natural growth of the children. Furthermore, an observer bias
      effect of the person who did the pricking on average wheal sizes was found. There
      were considerable differences in estimations of prevalences and incidences
      depending on the definition of SPT criterion. Estimations using a criterion based
      solely on the allergen wheal size were affected by variation of allergen wheal
      sizes caused by growth and observer effects. The ratio criterion was not
      influenced by observer effects, nor did it seem to be affected by aging effects.
      In conclusion, our data suggest that the ratio criterion, which relates the size
      of the allergen wheal to the size of the histamine wheal, is the most appropriate
      SPT criterion because it is not affected by growth of allergen wheals in
      childhood and it appears to compensate for possible observer bias.

PMID- 7825720
TI  - Fungal propagules in house dust. I. Comparison of analytic methods and their
      value as estimators of potential exposure.
AB  - The presence of viable mold propagules in house dust was investigated by 10
      different analytic methods, in order to determine to what extent different
      results are obtained when different analytic methods are used. Moreover, the
      value of this measurement as an estimator of the potential exposure to fungi in
      epidemiologic studies was assessed. Floor and mattress dust was sampled in 60
      homes in The Netherlands during autumn 1990. For investigation of the variability
      in time, sampling was repeated in 20 homes after 6 weeks. Each analytic method is
      characterized by a unique combination of culture medium, suspension medium, and
      dilution step. The highest mean number of colony-forming units (CFU)/g dust was
      obtained by suspension of at least 100 mg dust in a peptone or sucrose solution
      in a ratio of 1:50 (w/w), followed by 10-fold dilution and plating on DG18 agar
      (geometric mean (GM) approximately 60,000 CFU/g dust). The lowest mean number of
      CFU/g dust was obtained by direct plating of 30 mg dust on V8 agar (GM
      approximately 5300 CFU/g dust). The mean coefficient of variation of duplicate
      analyses varied from 11%, for suspension in sucrose and plating on DG18 agar, to
      27%, for suspension and dilution in sucrose in combination with V8 agar. The
      highest mean number of species isolated was obtained by direct plating of 30 mg
      dust on DG18 agar (mean number of species: 17). Suspension and dilution on DG18
      or V8 agars yielded an average of approximately six species. In duplicate
      analyses, the mean percentage of agreement for the species isolated varied from
      approximately 35%, for suspension and dilution, to 60%, for direct
      plating.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7825721
TI  - Fungal propagules in house dust. II. Relation with residential characteristics
      and respiratory symptoms.
AB  - As part of a case-control study on the relation between home dampness and
      respiratory symptoms of children, house-dust samples were collected from bedroom
      floors and mattresses in 60 homes in The Netherlands. The house-dust samples were
      analyzed for the presence of fungal propagules by plating 30 mg of dust directly
      onto DG18 agar. A checklist and questionnaire were used to obtain information on
      the home characteristics and occupant behavior that may have an effect on the
      presence of fungal propagules in house dust. The geometric mean (GM) numbers of
      colony-forming units (CFU)/g dust collected from the floors was 8990. The number
      of CFU/g dust was significantly higher in dust from carpeted floors than in dust
      from smooth floors (GM, respectively, 12,880 CFU/g dust and 3530 CFU/g dust). The
      GM number of CFU/g dust collected from mattresses was 6760. Overall, the mean
      numbers of CFU/g dust collected from floors and mattresses were higher in
      bedrooms where damp spots mold growth, or both were observed. However, these
      differences were not statistically significant. The relation between home
      characteristics and the number of CFU/g dust of the most frequently isolated mold
      species (n = 17), including Alternaria alternata, Cladosporium cladosporioides,
      Penicillium brevicompactum, and Scopulariopsis brevicaulis, was also
      investigated. Only the type of flooring had a significant and consistent effect
      on the number of CFU/g floor dust of the different mold species.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7825722
TI  - Prospective study of laboratory-animal allergy: factors predisposing to
      sensitization and development of allergic symptoms.
AB  - In a prospective study of laboratory technicians, selected indicators of allergy
      and atopy were studied in an attempt to determine predictors of laboratory-animal
      allergy (LAA). Laboratory technicians underwent spirometry, methacholine
      provocation tests, and blood sampling, and responded to a questionnaire during
      training and after 2 years' work. Among 38 laboratory-animal-exposed subjects,
      total IgE before exposure gave the best correlation (P < 0.01; Mann-Whitney U
      test) to reported symptoms caused by laboratory animals (n = 8) at follow-up. The
      prevalence of atopy and allergic symptoms had increased in exposed technicians at
      follow-up, but this was also found among unexposed matched referents (n = 36
      pairs). One subject in the exposed group reported asthma before exposure,
      compared with seven at follow-up (P < 0.05; Fisher's exact test). However, the
      prevalence of asthma had increased from two to six (not significant) also among
      unexposed technicians. There were no significant differences between the groups
      in any measured variable at follow-up. Among 43 subjects who later worked with
      laboratory animals, 21% had a positive skin prick test for common allergens, as
      compared with 37% among 112 without animal exposure (P = 0.06; chi2 test),
      suggesting selection for laboratory animal work.

PMID- 7825723
TI  - A comparative study of three serine proteases from Dermatophagoides pteronyssinus
      and D. farinae.
AB  - Studies have shown that the dust mites Dermatophagoides pteronyssinus and D.
      farinae contain several serine proteases, two of which have been shown to be
      allergenic, and to include trypsin and chymotrypsin, corresponding to the groups
      III and VI mite allergens. However, mites also contain other serine proteases,
      and the data reported in this study show that an elastase-like enzyme is present
      in both species. This enzyme was differentiated from the other serine proteases,
      particularly chymotrypsin, on the basis of charge, substrate specificity, and
      inhibition by copper and mercury cations. Its apparent mol. mass, as judged by
      gel filtration, was similar to those previously described for trypsin and
      chymotrypsin, i.e., 30 kDa. Several isoforms were detected by isoelectric
      focusing, but the isoelectric points of the major forms in both D. pteronyssinus
      and D. farinae were 10.5 and 9.8, respectively, contrasting with the acidic mite
      chymotrypsins. All three serine proteases were detected in whole mite and
      faecally enriched extracts, but the activities of trypsin and the elastase-like
      enzyme were greater in the latter type of extract. These data were similar to
      those obtained by quantitative immunochemical analysis of the D. farinae group
      III allergen in appropriate extracts, suggesting that culture conditions may
      modulate protease production. A monoclonal antibody affinity matrix specific for
      the group III allergen from D. farinae was shown to bind mite trypsin. However, a
      small amount of mite chymotrypsin also bound, suggesting limited immunologic
      cross-reactivity, a finding consistent with known sequence data.

PMID- 7825724
TI  - Food allergy to sunflower oil in a patient sensitized to mugwort pollen.

PMID- 7825725
TI  - Methotrexate in steroid-dependent asthma: long-term results.
AB  - Treatment of 21 steroid-dependent asthmatic patients with methotrexate (MTX) 15
      mg/week was prospectively evaluated for a mean of 14.7 (SD 3.7) months. Before
      MTX, therapy consisted of a mean prednisone dose of 16.6 (SD 9.2) mg, in addition
      to inhaled beclomethasone/budesonide (mean daily dose 1157 (SD 330) micrograms)
      and bronchodilators. Thirteen patients were weaned from all regular systemic
      steroid therapy, a 50% or more reduction was achieved in four patients, and a
      less than 50% reduction in four patients. Abnormal liver function tests were
      noted in six of the 21 patients; this resolved despite continuation of MTX in
      five. In one patient, MTX was stopped because of symptoms as well as a fivefold
      rise in serum transaminases, and a speedy resolution was noted. Gastrointestinal
      side-effects were reported in six patients but were resolved in five with
      intramuscular MTX. There were no hematologic or pulmonary complications. We
      conclude that MTX appears to be both safe and efficacious as a steroid-sparing
      agent in most steroid-dependent asthmatic patients when taken over a long period.

PMID- 7825726
TI  - Contamination of heparin by histamine: measurement and characterization by high
      performance liquid chromatography and radioimmunoassay.
AB  - Plasma samples which were collected in the presence of heparin contained 12.83 +/
      0.34 ng/ml histamine-immunoreactive material (n = 10). In contrast, histamine
      immunoreactive material in plasma samples which were collected in the presence of
      EDTA/phenanthroline contained 0.32 +/- 0.01 ng/ml (n = 10). Histamine
      immunoreactive material was found as a contaminant in three different heparin
      formulations with unrelated batch numbers. The concentrations of the histamine
      like material were 32.82, 81.93, and 280.23 ng/ml, respectively. Octadecasilyl
      silica (ODS) cartridges were used to purify histamine from other constituents in
      the heparin preparations. The histamine-immunoreactive material in the three
      preparations could be characterized as histamine with cation-exchange high
      performance liquid chromatography (HPLC) on a TSK SP-5 PW column with NaH2PO4,
      pH5.0, as a mobile phase and gradient elution. For the accurate measurement of
      histamine in plasma samples with heparin as an anticoagulant, one should be aware
      of a possible contamination of heparin formulations by histamine.

PMID- 7825727
TI  - Type III collagen is a major component of interodontoblastic fibers of the
      developing mouse molar root.
AB  - BACKGROUND: Recently, collagenous interodontoblastic fibers (IOF) were reported
      in some particular developmental stages and/or locations of the tooth. However,
      it remained unclear whether these fibers were identical to so-called von Korff
      fibers. METHODS: To clarify this issue, we examined the developing mouse molar by
      three-dimensional reconstruction of 8 confocal images within a 6 micron-thick
      section using laser scanning confocal microscopy, and confirmed our findings
      using immunoelectron microscopy. RESULTS: In the root pulp during circumpulpal
      dentin formation, the IOF stained weakly for type I collagen, but stained
      strongly for type III collagen by a double-staining technique. It could be
      clearly seen that many immunoreactive fibers ran spirally among the odontoblasts
      and entered the predentin. This distribution pattern of IOF was similar to that
      of the classical von Korff fibers. Furthermore, the existence of anti-type III
      reactive collagen fibrils between odontoblasts was confirmed, whereas IOF were
      not observed in the coronal pulp during circumpulpal dentin formation.
      CONCLUSIONS: This study presents for the first time, immunohistochemical
      observations which demonstrate the presence of IOF at least during root
      circumpulpal dentin formation and which reveal that type III collagen is a major
      component of IOF.

PMID- 7825728
TI  - Ultrastructural and immunocytochemical study on normal human palmar aponeuroses.
AB  - BACKGROUND: Human palmar aponeurosis can be affected by a fibrotic process whose
      aetiopathology is unknown. As the organization of that normal tissue has not been
      completely investigated, the aim of the present study was to define the
      ultrastructure of the aponeurosis in order to better understand its biology and
      behaviour in pathology. METHODS: Bioptic samples from normal subjects of
      different ages were analysed by optical and electron microscopy and by
      immunocytochemistry. RESULTS: The aponeurotic branches consisted of thick, almost
      parallel collagen bundles containing columns of prominent cells, characterized by
      long cytoplasmic projections. Cells did not change in number and distribution
      with age and appeared longer and slighter in the old than in the young subjects.
      They exhibited plasma membrane almost completely decorated by pinocytic vesicles,
      intracytoplasmic bundles of thin filaments with zonal thickenings close to the
      cell membrane, and well-developed subcellular structures. Cells expressed smooth
      muscle cell alpha-actin, as revealed by immunostaining. The external surface of
      the plasma membrane was underlined by a discontinuous basement membrane-like
      structure and by a thick coat of interwoven filaments, highly positive to
      hyaluronan-recognizing antibodies. Immunocytochemical analyses revealed that
      collagen fibrils were positive for collagen types I, III, and VI and that elastin
      fiber composition was rather complex. CONCLUSIONS: Independently of the age,
      normal palmar aponeurotic cells show peculiar morphological features and peculiar
      cell-matrix interactions, very likely mediated by hyaluronan. These findings
      indicate that normal aponeurotic cells cannot be regarded as typical tenocytes
      and suggest the need for a better definition of their phenotype in order to
      understand their behaviour in pathological processes.

PMID- 7825729
TI  - Ovarian surface epithelium during ovulatory and anovulatory ovine estrous cycles.
AB  - BACKGROUND: Ovarian surface epithelial cells have been implicated in the
      mechanisms of ovulation and development of common ovarian cancers. An early
      indication of predisposition to neoplasia is the formation of ovarian epithelial
      inclusion cysts. It was unclear whether morphological alterations along the
      ovarian surface are related directly to ovulation per se or associated endocrine
      parameters of reproductive cyclicity. METHODS: Light microscopic disturbances in
      ovarian surface epithelium were monitored during synchronous ovulatory and
      anovulatory estrous cycles of sheep. Ovulation blockade accompanied by normal
      luteal phases was induced by administration of indomethacin, a prostaglandin
      synthase inhibitor. RESULTS: Degenerative cells were sloughed from the apical
      dome of periovulatory follicles. The resultant stigma of luteinizing follicles
      was void of surface epithelium. Repair of the ovulatory wound by epithelium did
      not occur until complete involution of the corpus luteum during the subsequent
      estrous cycle. In a few cases inclusions containing entrapped ovarian surface
      epithelium were noted within adjacent stroma. Epithelia covering luteinized
      unruptured follicles remained intact and was not incorporated into the ovary
      during luteal resorption. CONCLUSION: Localized damage to and subsequent
      remodelling of the ovarian surface occurs in a cyclic fashion conjoined with the
      physical process of follicular rupture.

PMID- 7825730
TI  - Developmental expression of sulfated glycoprotein-2 in the epididymis of the rat.
AB  - BACKGROUND: Sulfated glycoprotein-2 (SGP-2), also designated as clusterin, is a
      protein secreted by the epididymis and which binds to spermatozoa. In adult rats
      it is secreted at high levels by principal cells of the distal initial segment,
      intermediate zone and caput epididymidis, and at relatively lower levels by
      principal cells of the corpus and cauda epididymidis. The objective of this study
      was to correlate the developmental events in the maturation of the epididymis
      with the timing of SGP-2 expression in order to evaluate the testicular or
      epididymal factors which may regulate it. METHODS: Our approach was to follow and
      compare the developmental expression of SGP-2 by immunocytochemistry in normal
      untreated control rats and rats whose efferent ducts were ligated on day 15 and
      examined at different postnatal ages thereafter. RESULTS: In control animals, SGP
      2 expression in principal cells of the distal initial segment, intermediate zone,
      and caput and distal cauda epididymidis, as characterized in normal 90-day-old
      adult animals, was attained between postnatal days 39 and 49. However, only by
      postnatal day 56 did SGP-2 display in the corpus and proximal cauda the
      characteristic secretory pattern found in adult rats. In contrast, in efferent
      duct ligated rats examined at postnatal day 64, SGP-2 was absent in principal
      cells of the corpus and proximal cauda epididymidis but continued to be secreted
      by the distal initial segment, intermediate zone, and caput and distal cauda
      epididymidis. Furthermore, unlike the case in control rats, SGP-2 was secreted at
      high levels by the principal cells of the proximal initial segment. Thus during
      normal postnatal development, in the proximal initial segment, the production of
      SGP-2 is suppressed by luminal factors originating from the testis, while in the
      distal initial segment, intermediate zone, and caput epididymidis, it is
      unaffected by these factors. On the other hand, the production of SGP-2 in the
      corpus and proximal region of the cauda epididymidis is normally stimulated by
      luminal factors originating from the testis, while in the distal cauda, it is
      unaffected by these factors. CONCLUSIONS: Our results thus show a differential
      regulation of SGP-2 expression in principal cells of the proximal versus distal
      regions of the epididymis and even within subdivisions of each region. In some
      regions of the epididymis, SGP-2 production appears to be unaffected by luminal
      factors originating from the testis, while in other regions it is either
      inhibited or stimulated by these factors.

PMID- 7825731
TI  - Developmental expression of the glutathione S-transferase Yo subunit in the rat
      testis and epididymis using light microscope immunocytochemistry.
AB  - BACKGROUND: Glutathione S-transferases (GSTs) are a family of isozymes that
      catalyze the conjugation of glutathione with various toxic electrophilic
      compounds. GSTs are composed of several classes based on the degree of sequence
      homology of their subunits. The Yo subunit, a member of the mu class, is
      expressed at high levels in the testis and epididymis. The purpose of this study
      was to immunolocalize the GST-Yo in these tissues during development. METHODS:
      The testes and epididymides of rats aged 7, 15, 21, 28, 39, 42, 45, 49, and 56
      days were fixed in Bouin's fixative, and immunostained for light microscopic
      analysis. RESULTS: In the testis the cytoplasm of all germ cells was unreactive
      until day 39. At that time, step 18 spermatids appeared moderately reactive,
      while the few observed step 19 spermatids were intensely reactive as were their
      residual bodies. The presence of residual bodies indicates that spermiation takes
      place as early as day 39; however, the number of step 19 spermatids is low at
      this age. A progressive increase in the size of the tubule and number of
      elongating spermatids was seen between days 42 and 49. In addition, by day 49, a
      weak staining was observed in steps 12-15, moderate in steps 16-17, and intense
      in steps 18-19 spermatids. In terms of the intensity of staining, cell types
      stained, size of the tubules, and number of elongating spermatids, no difference
      was noted between day 49, 56, and adult animals. Thus Yo protein expression in
      germ cells reached maturity by day 49. The epithelial cells of the rete testis
      were intensely reactive at day 7 and remained so throughout development. In
      contrast, while the epithelial cells of the efferent ducts at day 7 were
      intensely reactive, they were weakly reactive by day 39 and remained so at later
      ages. Along the entire epididymis, the columnar epithelial cells showed a
      moderate apical/supranuclear reaction from day 7 to 28. By day 39 principal cells
      of the initial segment became weakly reactive, while those in the caput and
      corpus were moderately stained, a situation seen at later ages including adults.
      Only by day 49 did principal cells of the proximal cauda become moderately
      stained as seen in adult animals. Thus the expression of the Yo protein in the
      principal cells of the proximal cauda may be regulated by different factors than
      those of the caput and corpus epididymidis. Alternatively, the expression of the
      Yo subunit in principal cells of the proximal cauda may develop later since this
      region would be the last to receive luminally derived testicular products. In the
      initial segment, the decrease in staining of principal cells at day 39 may be due
      to an inhibiting factor emanating from the testis. Spermatozoa appeared in the
      lumen of each epididymal region well after the expression of Yo had reached its
      adult staining pattern indicating that they are not a factor. CONCLUSIONS:
      Overall these results suggest that the expression of GST-Yo in the various cells
      of the testis and epididymis are controlled by different factors during postnatal
      development.

PMID- 7825732
TI  - Immunolocalization of a mesenchymal antigen specific to the gastrointestinal
      tract.
AB  - BACKGROUND: The aim of the present study was to localize, at the fine structural
      level, a protein found by indirect immunofluorescence to be associated with the
      mesenchymal tissue 1) closely applied to the intervillus epithelium before the
      formation of intestinal crypts in the mouse fetus and 2) around intestinal crypts
      during and after their formation. METHODS: We used a pre-embedding immunolabeling
      technique for extracellular matrix molecules, and a monoclonal antibody (Mab)
      directed against antigen MIM-1/130. RESULTS: Immunofluorescence disclosed the
      presence of antigen 1/130 in the connective tissue closely applied to the
      epithelium of the gallbladder, pyloric glands, and intestinal and colonic crypts
      in adult mice. The antigen was absent in all salivary glands, kidney, liver,
      lung, spleen, and pancreas. At the fine structural level, gold particles in
      positive organs were associated with the interstitial matrix around collagen
      fibrils underneath the epithelia; gold particles were completely absent in the
      basement membranes. In the small intestine, labeling was seen only around crypts
      from cell position 1 up to the crypt-villus junction; it was totally absent under
      the villus epithelium. In order to confirm this particular localization in vivo,
      Mab 1/130 was administered orogastrically to 9-day-old mice: after 3 hours the
      antibody was found lining the immediate periphery of duodenal crypts as seen by
      indirect immunofluorescence. In control animals, an anti-mouse laminin Mab of the
      same subclass as Mab 1/130 was orogastrically fed using the same protocol: basal
      laminae were labeled under the epithelium of duodenal villi and crypts and also
      in the lamina propria, with a decreasing gradient from the top of the villi to
      the bottom of the crypts. CONCLUSION: These observations indicate that the
      extracellular matrix associated with the epithelium of pyloric glands, of
      intestinal and colonic crypts, and of gallbladder contains a new antigen whose
      function remains to be determined. The neonatal mouse hence constitutes a good
      model to study the role of extracellular matrix components in determining organ
      differentiation in vivo.

PMID- 7825733
TI  - Observations on the pineal gland of the big brown bat, Eptesicus fucus: possible
      correlation of melanin intensification with constant darkness.
AB  - BACKGROUND: Our initial observation of the macroscopically pigmented pineal gland
      of the big brown bat, Eptesicus fuscus, led to this study. Information has been
      lacking on pigmentation in the pineal and its significance in mammals in general
      and bats in particular. This report begins to address this situation. METHODS:
      Bats were examined both in the wild and after exposure to various experimental
      conditions. The pineals were examined macroscopically as well as with light and
      electron microscopy. The pigment was identified as melanin by its color, the
      ultrastructure of its granules, and their reaction with hydrogen peroxide.
      RESULTS: Gross observations showed the pineals to be variably pigmented, which
      were subjectively scored from unpigmented to heavily pigmented. Pineals from bats
      exposed to a continuous 24 h light regimen or those from a summer population
      contained very little, if any, externally visible melanin. Such pineals are
      considered unpigmented in this study. In contrast, pineals from 74% of 156
      animals taken together, either subjected to constant darkness or hibernation
      (simulated or natural), exhibited very heavily pigmented pineals. The pigment in
      these cases even extended to the juxtapineal meningeal covering. The pineal was
      pigmented even in a newborn Eptesicus. CONCLUSIONS: The pineal pigmentation in
      the big brown bat appears to intensify with constant darkness and may vary
      seasonally. The observation of macroscopically pigmented pineals in some other
      bats (Myotis lucifugus, Pipistrellus subflavus, and Lasiurus borealis) suggests
      that this phenomenon may be of taxonomic value for the family Vespertilionidae
      (Order Chiroptera).

PMID- 7825734
TI  - Ontogeny of neurotransmitter systems in the paracervical ganglion and uterine
      cervix of the rat.
AB  - BACKGROUND: The paracervical ganglia (PG) are components of the pelvic plexus
      that provides sensory and motor innervation to the reproductive system of the
      female rat. Several neurotransmitters including norepinephrine (NE),
      acetylcholine (ACh), neuropeptide Y (NPY), and vasoactive intestinal polypeptide
      (VIP) are present in neurons of the adult PG and in axons innervating the adult
      uterus and uterine cervix. The current study was undertaken to describe the onset
      of immunoreactivity of these neurotransmitters and neuropeptides during
      development. METHODS: Female rats, ages E18 to P36, were prepared for
      immunohistochemistry for TH (tyrosine hydroxylase, a marker of noradrenergic
      neurons), NPY, or VIP as well as the histochemical demonstration of
      acetylcholinesterase (AChE). RESULTS: All four markers were detected in neurons
      of the PG at E18. Changes in the appearance of these markers from E18 to P36
      reflected previously described growth changes in the PG. Axons containing AChE,
      TH, NPY, or VIP were first detected within the cervix at E20. Immunopositive
      axons first appeared as thick, unbranched structures at the outermost portion of
      the cervical myometrium. Over time, these axon bundles ramified to form discrete
      varicose axons. The ingrowth was similar for axons containing each of the four
      markers. CONCLUSIONS: The relative density of each neuronal type in the PG was
      reflected in the density of axons containing the same marker in the cervix.
      Changes in neurotransmitter/neuropeptide staining of PG neurons or axons in the
      cervix were not observed as the animals approached puberty.

PMID- 7825735
TI  - Precursors of macrophages in embryonic rat lungs fail to exhibit granulocyte
      forming potential.
AB  - BACKGROUND: Mesenchyme-like macrophage (M) precursors called angular cells are
      present in rat lungs on the thirteenth day of gestation and by then can
      differentiate into outright macrophages. Based on studies of bone marrow-derived
      cells, it is widely believed that the macrophage line necessarily proceeds from a
      colony-forming unit with dual granulocyte-macrophage potential (CFU-GM). In
      embryos this seems doubtful since macrophages are already scattered throughout
      the body before the first granulocytes appear. We examined the question in organ
      cultured 14 day prenatal rat lungs after having shown earlier that the macrophage
      population developed in explants is increased by exposure to M- and GM-colony
      stimulating factors (CSFs) but is unaffected by multi (IL-3)- or granulocyte (G)
      CSF. Reportedly retinoic acid (RA) shifts CFU-GM strongly towards granulocytic
      differentiation and inhibits mitosis of unipotential macrophage precursors but
      not differentiated cells. Transforming growth factor beta 1 (TGF) inhibits
      multipotential blood progenitors but allows proliferation of committed
      precursors, and TGF together with GM-CSF induces granulocytopoiesis from CFU-GM.
      METHODS: Lung pairs were grown on a serum-containing medium or one supplemented
      either by RA, TGF, or TGF/GM-CSF to form a control and three experimental groups.
      A fourth experiment compared responses to M-CSF exposure and M-CSF/TGF.
      Macrophage population growth was estimated by measuring the areas of coronas
      formed by macrophages emerged from the explants. F-actin was stained with
      fluorescein-labeled phalloidin. RESULTS: In all experiments macrophages were
      produced unmixed with granulocytes. By +8 days they had largely emerged to form
      coronas about the lungs. In cultures exposed to RA, macrophages were less
      intensely stained for actin and slower to emerge than controls. At +8 days,
      however, coronal areas were not significantly different from controls, as was
      also true for the TGF group. In contrast, coronal areas of cultures grown with
      TGF/GM-CSF were much larger. At +17 days, mean coronal area of TGF cultures was
      about half that of controls (P < 0.05), whereas mean coronal area of the TGF/GM
      CSF group was 5.4 times greater (P < 0.001). Macrophages from control and TGF
      exposed cultures responded to M-CSF by an increase in coronal area which was
      greater among cultures given M-CSF alone than those given TGF + M-CSF (both P <
      0.005). CONCLUSIONS: Macrophage precursors in embryonic lungs are distinct from
      CFU-GM.

PMID- 7825736
TI  - Exogenous cytokines enhance survival of macrophages from organ cultured embryonic
      rat tissues.
AB  - BACKGROUND: Macrophage precursors are present in embryonic rats shortly after the
      onset of hematopoiesis. During organogenesis they soon establish residency in
      many parts of the body and become convertible into phagocytes, at first gaining
      morphological characteristics of macrophages and later a range of surface
      antigens used to characterize subpopulations in adults. Nonetheless, it is
      uncertain whether representatives of this fetal lineage continue to exist past
      birth. We investigated the question indirectly by seeing if such cells can be
      made to survive in vitro to an age equivalent to adulthood and by examining
      underlying conditions that favor this outcome. METHODS: Fourteen-day embryonic
      lungs, hearts, and limb buds were organ cultured on a firm serum-containing
      medium. Fetal macrophages developed within all explants and then migrated out to
      form a corona of cells surrounding each explant. The lung cultures were selected
      for subsequent work which mainly used coronal area as the measure of macrophage
      population size in experimental and control groups. Baseline growth and survival
      of macrophages were established for cultures grown on standard medium, then
      effects of the following were examined: indomethacin (10(-6) M) as it influences
      initial production of macrophages from precursors and later survival of
      differentiated cells; and macrophage colony-stimulating factor (M-CSF), used
      alone at moderate dosage (50-100 U), and combined with granulocyte-macrophage CSF
      (both 200 U), for its importance to long-term survival of the population.
      Mitogenic influence of M-CSF on differentiated macrophages was demonstrated by
      uptake of 5-bromo-2'-deoxyuridine. RESULTS: Indomethacin inhibited the formation
      of macrophages from precursors but enhanced the survival of differentiated cells.
      M-CSF increased BrdU uptake of differentiated macrophages and permitted coronal
      growth to continue long past the approximately 30 day limit of controls. Beyond
      this interval, M-CSF was essential for macrophage survival, since coronas quickly
      shrank after the cytokine was withdrawn. Administration of the M-CSF/GM-CSF
      mixture to the 2 oldest M-CSF-exposed cultures between 98 and 127 days in vitro
      resulted in an increase in the number of coronal macrophages (P < 0.001);
      withdrawal between 129 and 140 days led to a decrease (P < 0.005). Ultimately a
      few cells were still surviving at 183 days. CONCLUSIONS: Intrinsic factors
      promote early formation of macrophages within the explants, but the availability
      of factors is lessened by the anti-inflammatory action of indomethacin. Its later
      promotion of macrophage survival may be based on suppression of autogenous
      prostaglandin (PGE2) synthesis. M-CSF greatly promotes macrophage survival; in
      context this is sufficient to show that the fetal macrophage line has a clear
      potential to survive well into adulthood.

PMID- 7825737
TI  - Composition of Gomori-positive inclusions in astrocytes of the hypothalamic
      arcuate nucleus.
AB  - BACKGROUND: Astrocytes within the hypothalamic arcuate nucleus contain Gomori
      positive inclusions that exhibit a nonenzymatic peroxidase activity. The source
      and composition of these Gomori-positive inclusions are currently unknown. Recent
      evidence, derived from cultured astrocytes, suggests that Gomori-positive
      inclusions may consist of autophagocytized accumulations of altered mitochondria
      and that the peroxidase activity is generated by iron or other metals which
      accumulate in these mitochondria. METHODS: The present study applies electron
      microscopy, energy dispersive X-ray microanalysis, and immunocytochemistry in
      conjunction with confocal microscopy to determine the structure and composition
      of Gomori-positive inclusions in vivo. RESULTS: The results indicate that Gomori
      positive inclusions are heterogeneous structures often associated with
      microtubules and that they contain conspicuous mitochondrial components. Gomori
      positive inclusions exhibit X-ray emission peaks for copper and, less often,
      chromium, either of which could account for the peroxidase activity. CONCLUSIONS:
      These results support the hypothesis that Gomori-positive inclusions are
      autophagosomes in which mitochondria are prominent.

PMID- 7825738
TI  - Embryological development of the arterial system of the forelimb in Tupaia.
AB  - BACKGROUND: The arterial system of the upper extremities in man shows drastic
      developmental changes and many individual variations related to interspecific
      variations in primates. The ontogenetic development in Tupaia was examined from
      the viewpoint of comparative embryology. METHODS: Histological specimens of 39
      embryos were observed and reconstructed in three dimensions using a computer
      program. Four adult animals were dissected and examined with angiography to
      ascertain the end stage of development. RESULTS: At the proximal end of the upper
      arm the deep brachial artery appears first as a concomitant vessel with the
      radial nerve. It becomes reduced in size and is succeeded by the posterior
      circumflex humeral artery, which is accompanied initially by the axillary nerve
      and finally by the radial nerve. The main arterial passageway to the fingers
      consists of the brachial and interosseous arteries during early development. The
      superficial brachial artery and median artery are formed later, and their
      connection becomes the main route of blood supply for the finger arteries up to
      the adult stage. The ulnar artery is formed at the end of arterial development to
      form the ulnar end of the superficial palmar arch. The superficial antebrachial
      arteries are also recognized. CONCLUSIONS: All the arterial elements of the
      forelimb in Tupaia are observed in a variety of primates, including man, and the
      characteristics of Tupaia are thought to represent the primitive conditions of
      the common ancestor of tree shrews and primates.

PMID- 7825739
TI  - Morphological and kinematic study of the tongue and buccal cavity in the lizard
      Anguis fragilis (Reptilia:Anguidae).
AB  - BACKGROUND: The ability to detect chemical cues is highly developed in
      Scleroglossa, and particularly in anguid lizards. This ability was predicted
      because anguids possess a well-developed vomeronasal organ (VNO) (or Jacobson's
      organ) and rely largely on chemical cues in various behaviours as other active
      foragers. In this work, we have investigated the possible functional association
      between tongue flicking and the VNO in the lizard Anguis fragilis. METHODS: The
      morphology of the tongue and the buccal cavity was investigated by light and
      scanning electron microscopy. The kinematics of tongue and jaw movements was
      studied by high speed cinematography. RESULTS: The epithelial cells of the
      ventral aspect of the tongue tips show microstructures (microridges, microfacets,
      micropores) which are not present on other areas of the mouth. Beneath the
      tongue, the floor of the buccal cavity shows two concave-like elevations
      suggesting a structural analogy with the anterior processes described in snakes.
      The apex and the internal margin of these processes bear parallel oblique ridges.
      Taste buds occur anteriorly on the buccal floor and on the palate and are
      abundant on the internal side and on the edge on the anterior processes. The
      tongue showed three modes of tongue flicking: simple downward extension, single
      oscillation, and multiple oscillations. At each tongue flick, the ventral surface
      of the tips was observed contacting the substratum. Immediately after the tongue
      retraction, the buccal floor moved slightly upward. The observation of tongue
      flicking with the mouth open showed that the anterior processes moved upward when
      the tongue was retracted. CONCLUSIONS: These observations suggest that following:
      1) during tongue flicking the ventral surface of the tongue tips invariably makes
      contact with the substratum; 2) the microstructures of the tongue tips and the
      ridges of the anterior processes might be helpful for collecting and receiving,
      respectively, chemicals during tongue flicking; 3) the anterior processes may be
      apposed on the roof of the mouth next to the ducts of VNOs when the buccal floor
      is fully elevated; 4) due to their localization, the taste buds could be equally
      stimulated by the molecules transferred during tongue flicking.

PMID- 7825740
TI  - Microvasculature of the human testis in correlation to Leydig cells and
      seminiferous tubules.
AB  - The microvasculature of the human testis is closely related to the Leydig cells
      and the seminiferous tubules. Semi-thin sections of testicular tissue serve as a
      basis for the computer-aided 3-D reconstruction of the microvasculature, the
      seminiferous tubules and the Leydig cells. After vascular perfusion with
      glutaraldehyde (5.5%) and paraformaldehyde (4%), it is possible by means of light
      and electron microscopy, to analyse the organization of the capillaries between
      the Leydig cells (inter-Leydig cell capillaries) as well as of those within the
      lamina propria (intramural capillaries). These arise from arterioles, deriving
      from branches of the segmental arteries. The capillaries ramify between the
      Leydig cells and run either semi-circumferentially around the seminiferous
      tubules (peritubular capillaries) or penetrate the lamina propria of the
      neighbouring tubules. This is the beginning of the intramural capillary which
      after leaving the tubular wall continues to a further capillary path.
      Consequently, the microvasculature of the human testis with regard to the
      seminiferous tubules is subdivided into afferent, intramural and efferent
      capillaries. Leydig cell clusters are present on both the arterial and the venous
      sides of the microvasculature.

PMID- 7825741
TI  - Significance of sperm antibodies detected by the mixed antiglobulin reaction and
      the tray agglutination test.
AB  - The most widely used tests to detect seminal and serum sperm antibodies are the
      mixed antiglobulin reaction (MAR as recommended by WHO) and the tray
      agglutination test (TAT). It has been suggested that the prognostic significance
      of sperm antibody tests might be influenced by a concomitant reduction of sperm
      numbers and/or sperm motility. Furthermore, the relative sensitivity of these
      sperm antibody tests to detect sperm antibodies is not known. We therefore
      compared TAT, performed with serum and MAR results retrospectively for 565
      infertile patients and MAR IgA and MAR IgG results for 1189 infertile patients.
      The association of TAT and MAR results with changes in sperm number, morphology
      and motility was assessed for 565 and 1185 patients, respectively. The influence
      of MAR and TAT results on sperm cervical mucus penetration test (SCMPT) results
      was investigated for 349 and 434 patients, respectively. Whereas only 23% of all
      MAR IgG positive patients were also MAR IgA positive, 82% of all MAR IgA positive
      patients were also MAR IgG positive. There was a significant (P < 0.0001)
      correlation between serum TAT, and MAR results. Positive MAR and TAT results were
      not associated with reductions in sperm number, motility and morphology. There
      was a significant correlation between MAR IgG and MAR IgA results and the sperm
      cervical mucus penetration test (SCMPT) results. According to these results, the
      MAR IgG would be sufficient as an initial screening for seminal sperm antibodies.
      MAR IgG negative patients with strong indication for immunologic infertility
      should also be investigated with the MAR IgA and the serum TAT.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7825742
TI  - Sperm acrosin levels in semen: comparison between ACCU-SPERM and Kennedy's
      methods.
AB  - The purpose of this experiment was to evaluate the accuracy, specificity, and
      sensitivity of a new acrosin activity assay, ACCU-SPERM, and to correlate these
      results with the original Kennedy method. Thirty-nine specimens (26 patients and
      13 donors) of 54 (72%) were found to be in the normal range (> 25 microIU
      acrosin/10(6) sperm) by the Kennedy method; the other 15 specimens were in either
      the indeterminate or subfertile range (< 14 microIU). However, according to the
      ACCU-SPERM method, (normal: 6.6-27 AAI; infertile: < 3.6), 90% of specimens (49
      of 54) whose acrosin activity was measured were in the subfertile or infertile
      range. Similarly, only 28% (4 of 14) of donors in the ACCU-SPERM method were in
      the normal range in contrast to the 93% (13 of 14) in Kennedy. After calculating
      the ACCU-SPERM normal range in our laboratory using the linear regression curve
      between the acrosin values generated by the Kennedy and ACCU-SPERM methods, we
      again compared results of the two methods. The new normal range of > 1.82 AAI in
      ACCU-SPERM corresponded to > 25 microIU in the Kennedy method; similarly a value
      of < 1.35 AAI in ACCU-SPERM corresponded to < 14 microIU in the Kennedy
      technique. Analysis of the results generated by the two methods revealed a poor
      correlation with a positive concordance of 51% and a negative concordance of 50%
      in both assays. These results strongly suggest that the ACCU-SPERM method for
      measurement of acrosin activity is not a reliable assay.

PMID- 7825743
TI  - Sperm binding capacity of human zona pellucida derived from oocytes obtained from
      different sources.
AB  - The important contributions of sperm-oocyte interaction to infertility
      diagnostics is well established. Scientists are urged to search for methods to
      improve the assessment of gamete interaction. Sperm binding and penetration
      assays have frequented the literature, reporting on various aspects of sperm
      oocyte interaction using either microbisected or whole human oocytes during the
      assay procedure. The objective of the study was to evaluate additional zona
      pellucida sources which can be used during zona binding studies. Hemizonae were
      obtained from the following oocytes: 1) experiment 1, prophase I oocytes from
      post-mortem ovarian tissue from different age groups namely, 7 months, 5 years, 7
      years, 12 years and 30 years; 2) experiment 2 used donated immature Prophase I
      oocytes from the IVF treatment program and 3) experiment 3 evaluated zona binding
      for hemizonae which were previously used in hemizona assays. Results indicated
      that, in experiment 1, ovarian age does not have any influence on the zona
      pellucida's capacity to bind spermatozoa. The mean number of bound sperm among
      the different age groups did not differ significantly, namely 38.9 +/- 17 (7
      months), 31.0 +/- 27 (5 years), 49.3 +/- 21 (7 years), 32.8 +/- 18 (12 years) and
      39.5 +/- 17 (30 years). The pooled mean +/- SD binding for all the age groups in
      experiment 1 was 37.7 +/- 7. Likewise, the mean number of sperm bound (experiment
      2) to zonae collected from oocytes using different ovulation induction regimes
      were 31.1 +/- 20 (unstimulated), 54.4 +/- 12 (HMG/HCG) and 15.3 +/- 9 (HMG
      alone).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7825744
TI  - Chemiluminescence in semen of infertile men.
AB  - Luminol-dependent chemiluminescence (CL) can be used to determine the production
      of reactive oxygen species (ROS) by cells. Enhanced formation of ROS in human
      semen was reported to be of pathological significance for a disturbed sperm
      function. To investigate incidence of elevated CL-signals in semen samples and
      their correlation to conventional semen parameters, CL-signals in the semen of
      both 49 consecutive infertile men and 20 controls were measured. Semen was
      analysed according to WHO-criteria including bovine mucus-penetration- and water
      test. A CL-signal of 1.5 x 10(5) counts min-1/2 x 10(6) spermatozoa was
      considered to be the upper normal limit. The CL in infertile men's semen was
      elevated with statistically significant differences in oligozoospermia
      patients/controls (P < 0.0001) and normozoospermia patients/controls (P < 0.05).
      In the group with elevated CL-signals, a higher percentage of spermatozoa with a
      pathologic morphology was detected (P = 0.05). In the groups with pathologic
      results of eosin- and water-tests, the CL-counts were elevated (P < 0.006; P <
      0.03). The spermatozoa motility in the group with elevated CL-counts was
      significantly reduced after 4 h (P < 0.05). The CL-signals correlated inversely
      with the results of the bovine mucus-penetration-test (r = -0.67), P < 0.0001).
      In conclusion, semen samples of 28% of our patients showed elevated CL-signals;
      these were associated with pathological results of membrane integrity-tests. The
      negative correlation of CL with the results of Penetrak-test reflects its
      importance to depict the functional capacity of spermatozoa.

PMID- 7825745
TI  - The enzymatic degradation of bradykinin in semen of various species.
AB  - The degradation of bradykinin in semen and on washed sperm cells of various
      species (human, pig, cattle, sheep) is mainly controlled by two peptidases, the
      angiotensin-converting enzyme (ACE/kininase II; E.C. 3.4.15.1) and neutral
      metalloendopeptidase (NEP; E.C. 3.4.24.11). In addition, minor activities of
      kininase I (carboxypeptidase N/CPN; E.C. 3.4.17.3) were measured exclusively in
      human samples. Samples of the investigated species varied considerably in their
      ratios of the activities of bradykinin degrading peptidases. This should be
      considered in any approach aimed at maintaining the promoting effect of
      bradykinin on sperm motility by use of enzyme inhibitors.

PMID- 7825746
TI  - Ovarian stimulation protocol and the outcome of in vitro fertilization are not
      related to the ability of follicular fluid to induce sperm acrosome reaction.

PMID- 7825747
TI  - 1993 Whitaker Lecture: biorheology in thrombosis research.
AB  - A review is presented on biorheological studies of platelet activation and
      platelet-platelet binding events that play key roles in thrombosis and
      hemostasis. Rheological methods have been used by a number of workers to
      establish the importance of fluid mechanical shear stress as a determinate of
      platelet reactions. Fluid mechanical shear stress can be regarded as a platelet
      agonist that is always present in the circulation and that is synergistic in its
      actions with other agonists. Early biorheological studies were phenomenological
      in that they focused on stress effects on measures of platelet function.
      Subsequent studies have elucidated mechanisms and have shown that the biochemical
      pathways of platelet activation are very different at elevated shear stresses
      than in the low shear stress environment used in many platelet activation
      studies. This finding that biochemical pathways of platelet activations are
      different at different shear stress levels suggests that it may be possible to
      develop platelet inhibitors of highly specific action: it may be possible to
      inhibit pathways important in thrombosis in a partially occluded artery without
      seriously compromising the normal hemostatic function of platelets. Another
      aspect of the work suggests that the biorheological approach may make it possible
      to develop better methods for prediction of thrombotic tendencies in human
      subjects.

PMID- 7825748
TI  - Shear rate and hematocrit dependence of fluorescence from retinal vessels in
      fluorescein angiography.
AB  - The purpose of this work was to obtain more quantitative knowledge about the
      yield of fluorescence from retinal vessels during fluorescein angiography. The
      influence of shear rate, concentration of sodium fluorescein, hematocrit, and
      layer thickness on the yield of fluorescence from blood were investigated.
      Measurements were performed in vitro on samples of human blood in a cone-plate
      shear chamber using frontal illumination. Application of physiologically relevant
      levels of shear (> 88/sec) decreased the yield of fluorescence from the blood
      sample considerably as compared with stasis. The yield of fluorescence was
      proportionally related to the logarithm of the sodium fluorescein concentration
      in blood up to a sodium fluorescein concentration of 1.2 mg/ml. Above that
      concentration quenching occurred. An increase in layer thickness at a hematocrit
      of 45% resulted only in an increase of the yield of fluorescence up to a layer
      thickness of 25 microns. In conclusion, the sodium fluorescein concentration in
      blood is the only important factor that determines the yield of fluorescence from
      the larger retinal vessels in the successive phases of the fluorescein angiogram
      in a subject with a given hematocrit and hemoglobin concentration. The yield of
      fluorescence from retinal vessels (> 25 microns) is proportionally related to the
      logarithm of the sodium fluorescein concentration over a broad range of
      concentrations.

PMID- 7825749
TI  - A compartmental model for oxygen-carbon dioxide coupled transport in the
      microcirculation.
AB  - We present a multicompartmental model for an oxygen-carbon dioxide transport
      system. The compartmental equations and their lumped parameters are derived
      through space averaging of the corresponding distributed model. The model can
      predict compartmental distributions of oxygen and carbon dioxide partial
      pressures, oxygen-hemoglobin saturation, and pH. Other unique features include
      the effects of the radial distribution of partial pressures and the difference in
      metabolic rates between vessel wall and tissue. A model for the cat brain, based
      on this formulation, is compared with results of experiments and with two types
      of earlier models: one without space averaging and one without carbon dioxide
      transport. The results suggest that space averaging the convective terms
      significantly affects the behavior of the model. This is consistent with
      conclusions from our earlier oxygen-only model. Our observations also
      demonstrate, however, significant differences between the results from the oxygen
      carbon dioxide model and the oxygen-only model. For instance, at low blood flow
      rates or at low level of oxygen input, predicted oxygen partial pressures can
      differ by as much as 30% between the two models. Results obtained from the
      present model are supported by available experimental findings.

PMID- 7825750
TI  - Localized spatial discrimination of epicardial conduction paths after linear
      transformation of variant information.
AB  - We present a method for the localized statistical discrimination of class
      populations based on the Karhunen-Loeve and Fukunaga-Koontz transforms. These
      transforms provide features that model the variance of a sample distribution. The
      spatial series of a 196 channel epicardial electrogram recording from an
      arrythmogenic postinfarct canine were analyzed. For each type of rhythm studied,
      Karhunen-Loeve and Fukunaga-Koontz expansions were computed from five training
      sets of spatial data, corresponding to five locations across the surface of the
      heart. Nonparametric statistical tests were then used for discriminant analysis
      to compare properties representative of the distribution from each proposed
      class. In a comparison of properties from sinus rhythm to those of two
      ventricular tachycardias, several spatial regions exhibited statistically
      significantly different propagation characteristics. These areas were observed by
      visual inspection of electrogram activation maps to be characterized by
      conductive gradients, which differed in magnitude and direction from one rhythm
      to another. The regions in which the propagation characteristics are of greatest
      difference in each tachycardia were centered upon sites of conduction block,
      manifested by reentrant circuit rhythms. Therefore, the importance of the
      technique for the localization of specific electrophysiologic events is
      demonstrated. This study extends previous work of our group on biosignal pattern
      recognition to encompass localized spatial data.

PMID- 7825751
TI  - Dynamics of the sounds caused by partially occluded femoral arteries in dogs.
AB  - Previous studies have indicated that partially occluded arteries produce sounds
      due to turbulence. If these sounds from the coronary arteries could be detected
      externally, they would provide a simple approach to the detection of coronary
      artery disease. To confirm the hypothesis that coronary stenosis produces
      detectable acoustic correlates, sounds caused by a controlled occlusion of the
      femoral artery of dogs were detected and analyzed using both the fast Fourier
      transform (FFT) and the autoregressive (AR) methods. The femoral artery was
      chosen, since its size and flow approximate those of coronary arteries in humans.
      The poles of the AR spectra and the power ratios of different sections of the FFT
      and AR spectra were used to differentiate the degree of the stenosis. The results
      showed that high frequency acoustical power between 200 and 800 Hz is associated
      with the turbulence produced by the partially occluded femoral arteries of the
      dogs. Using the AR method, high acoustic power above 200 Hz increased when the
      degree of the occlusions increased. The poles and power ratios of the AR spectra
      differed according to the degree of stenosis. However, the high frequency
      acoustical power above 200 Hz did not increase above the 85% occlusion.

PMID- 7825752
TI  - Time-frequency spectral representation of the EEG as an aid in the detection of
      depth of anesthesia.
AB  - A time-frequency spectral representation (TFSR) has been used to study the
      nonstationary information in the EEG as an aid in determining the anesthetic
      depth. This paper uses a TFSR with an exponential weighting function for the
      purpose. Raw EEG data were collected form 10 mongrel dogs at various levels of
      halothane anesthesia. Depth of anesthesia was tested by observing the response to
      tail clamping, which is considered a supramaximal stimulus in dogs. A positive
      response was graded as awake (depth 0), and a negative response was graded as
      asleep (depth 1). The EEG obtained during a period of 30 sec tail clamp was
      processed into TFSRs. It was observed that at depth 0, the spectrum becomes
      localized in time and frequency. The percentage of energy in the delta (1-3.5 Hz)
      and theta (3.5-7.5 Hz) frequency bands increased. At depth 1, the spectrum
      remained unchanged throughout the period of tail clamp. The performance of the
      TFSR in detecting the patient's awareness was also compared with the power
      spectrum. It was concluded that under certain anesthetic conditions, the TFSR is
      superior to the power spectrum.

PMID- 7825753
TI  - Stroke volume measurement during supine and upright cycle exercise by impedance
      cardiography.
AB  - This study evaluated impedance cardiography (ZCG) estimates of stroke volume (SV)
      during exercise. Seven subjects were studied at rest and during progressive cycle
      exercise in supine and upright positions. SV was determined by ZCG (SVZCG) during
      exercise and for the first 5 cardiac cycles following exercise. SVZCG was
      compared with separate measurements of SV by CO2 rebreathing (SVCO2). Static
      blood resistivity (p) was measured at each level of exercise. No significant
      differences were found between supine exercise and immediate post-exercise values
      for the peak of the first derivative of the impedance change (dZ/dtmax), left
      ventricular ejection time (LVET), or SVZCG. Small differences in dZ/dtmax and
      SVZCG, but not LVET, were found in exercise to post-exercise cycling in the
      upright position. Intra-individual SVZCG and SVCO2 were moderately correlated
      (upright mean r = 0.64, supine r = 0.42) from rest to 70% of peak VO2. Similar
      correlations were found between Pulse-O2 (VO2/heart rate, used as an index to SV)
      and both SVZCG (upright r = 0.73, supine r = 0.57) and SVCO2 (upright r = 0.8,
      supine r = 0.65). The ZCG parameters dZ/dtmax and LVET correlated better with
      Pulse-O2 (dZ/dtmax: upright r = 0.92, supine r = 0.73; LVET: upright r = -0.9,
      supine r = -0.9). SVZCG calculated with the Kubicek equation performed as well as
      SVCO2. ZCG might be a superior method if the inversely correlated parameters,
      dZ/dtmax and LVET, were not expressed as a product to calculate SV.

PMID- 7825754
TI  - A study of optimal configuration and control of a multi-chamber balloon for
      intraaortic balloon pumping.
AB  - Balloon configuration and control scheme are important for the optimization of
      assistance of the failing heart with an intraaortic balloon pumping device. In
      this work, the configuration of a multi-chamber balloon and control schemes have
      been investigated by using a hemodynamic model and computer simulation methods.
      Following the simulation study, physical testing and animal experiments were
      performed to demonstrate the simulation results. Results show that the optimal
      configuration and controlled multi-chamber balloon can provide better assistance
      to the failing heart. Based on the simulation and experimental results, it was
      found that the shape of the rear chamber of a multi-chamber balloon is critical.
      The optimal control scheme was to inflate the rear chamber first and deflate it
      last.

PMID- 7825755
TI  - Progression of osteoporosis in cancellous bone depending on trabecular structure.
AB  - Progression of osteoporosis is caused by a decline in bone formation activity
      relative to the resorption activity. In this paper, the authors carried out a
      theoretical analysis of the progression of osteoporosis to estimate the
      osteoporotic change in the upper end of the femur. According to this analysis,
      the progression rate of osteoporosis in cancellous bone depends on the product of
      remodeling activity, Ract, and the trabecular structure parameter, Ktr. To
      confirm that the theoretical results were reasonably comparable to actual
      osteoporotic change, these two factors were measured in rabbits. From the
      results, it was concluded that the highest progression rate was shown in bar/bar
      like trabecular structure (type 3); the next highest rate, was shown in plate/bar
      like structure (type 2); and the plate/plate-like structure (type 1) was the most
      insensible. Furthermore, the bone volume fractions of cancellous bone were
      measured at the upper end of human femurs with and without osteoporosis. Then the
      measured value was compared with the theoretical value for each type of
      trabecular structure. Results showed that the decrease in bone volume fraction
      predicted by Eq. 7 was well in accord with the actual decrease.

PMID- 7825756
TI  - Resistance of fetal membranes to concentrated force applications and
      reconciliation of puncture and burst testing.
AB  - To further the characterization of the chorioamniotic membrane's physical
      properties, we assessed its ability to withstand a concentrated force. Probes of
      various diameters were used to puncture 275 specimens from 11 membranes. Values
      for "strength"/thickness, "stiffness"/thickness, and "toughness"/thickness all
      showed positive linear correlations (p < 0.001) with the increase of d/D, the
      ratio of probe diameter to specimen diameter. "Ductility" was independent of
      diameter, though a logarithmic regression did fit the data marginally (p < 0.05).
      The separate fracture of the amnion and chorion, which is reflected in ductility
      measurements, results in an increase in the distance the membrane can be
      deflected in vitro. In vivo, this behavior would translate to a reduction of
      pressure exerted on the remaining membrane, while the integrity of the protective
      sac is maintained. The data pool of mechanical characteristics was enlarged by
      reconciling data that were gathered by either of two testing methods: puncturing
      or bursting; the latter method involves the application of force over the entire
      surface of the test specimen.

PMID- 7825757
TI  - [Metal concentrations in benthic marine algae in 3 regions of the state of Rio de
      Janeiro].
AB  - The concentrations of zinc, cadmium and copper were determined in different
      benthic algal species from some sites located in Guanabara Bay, Sepetiba Bay and
      Ribeira Bay (State of Rio de Janeiro). The aim is to verify the possibility of
      using algae as indicators of metallic contamination in these areas. According to
      our results, the highest concentrations of Zn and Cd in algae were observed in
      Sepetiba Bay. In this region, the differences among the concentrations of the
      metals were analysed in three sampling sites. Padina gymnospora was the species
      recommended to monitor the contamination of Zn and Cd in Sepetiba Bay, for the
      following reasons: 1) its great abundance and distribution in the areas, and 2)
      its high ability to accumulate metals. More studies are suggested to evaluate the
      levels of metals in Guanabara Bay.

PMID- 7825758
TI  - Hepatitis B virus strains with mutations in the core promoter in patients with
      fulminant hepatitis.
AB  - OBJECTIVE: Fulminant hepatitis B can be induced by hepatitis B virus (HBV)
      strains with mutations in the precore region that cannot encode hepatitis B e
      antigen (HBeAg). Such mutations are rarely seen in HBV DNA clones from patients
      with fulminant hepatitis B in the United States and France. Thus, the other
      mutations in HBV strains causing fulminant hepatitis B need to be identified.
      DESIGN: Retrospective clinical, serologic, and molecular biological studies of
      patients with fulminant hepatitis B. SETTING: University and city hospitals in
      Japan. PATIENTS: 43 patients with fulminant hepatitis B. MEASUREMENTS: The
      precore region coding for a part of the HBeAg precursor and the core promoter
      regulating the transcription of precore messenger RNA were sequenced in HBV DNA
      clones. RESULTS: A point mutation from G to A at nucleotide 1896 in the precore
      region was detected in 519 (98%) of 529 HBV DNA clones from 38 patients. Two
      point mutations in the core promoter, from A to T at nucleotide 1762 and from G
      to A at nucleotide 1764, were detected in all 130 clones from the remaining 5
      patients, who did not have mutations in the precore region, and in 20 (63%) of 32
      clones from a patient with chronic hepatitis B who had transmitted HBV to 1 of
      these other 5 patients. Mutations in the core promoter were also detected in
      clones from 26 (68%) of the 38 patients with the precore mutation at nucleotide
      1896. Neither HBeAg nor antibody to HBeAg was detected in 37 (90%) of the 41
      patients tested. CONCLUSIONS: In Japan, fulminant hepatitis B is closely
      associated with HBV strains that do not produce HBeAg because of mutations in the
      precore region, which affect translation of HBeAg, or because of mutations in the
      core promoter, which affect transcription of the HBeAg coding region.

PMID- 7825759
TI  - Vascular outcome in men with asymptomatic retinal cholesterol emboli. A cohort
      study.
AB  - OBJECTIVE: To determine whether asymptomatic retinal cholesterol embolism is a
      risk factor for vascular events. DESIGN: Cohort study with retrospectively
      selected controls. SETTING: A Veterans Affairs medical center. PATIENTS: 70
      consecutive patients with asymptomatic retinal cholesterol emboli on dilated
      ocular examination in an eye clinic and 70 controls without retinal emboli.
      Controls were matched to patients for sex; age; prevalence of hypertension,
      diabetes mellitus, and ischemic heart disease; serum cholesterol level; and
      smoking history. MEASUREMENTS: Stroke, myocardial infarction, and death. RESULTS:
      During a mean follow-up of 3.4 years, stroke occurred at an annual rate of 8.5%
      among patients and 0.8% among controls (adjusted relative risk, 9.9; 95% CI, 2.3
      to 43.1; P = 0.002). Nineteen strokes occurred, 17 in patients and 2 in controls;
      all were nonfatal cerebral infarctions. Twelve of the 17 that occurred in
      patients were in a carotid artery territory ipsilateral to the qualifying retinal
      cholesterol embolus and 5 were in another vascular territory. Ocular infarction
      or hemorrhagic stroke did not occur. Nonfatal myocardial infarction or vascular
      death occurred at an annual rate of 7.7% among patients and 4.9% among controls
      (adjusted relative risk, 1.4; 95% CI, 0.7 to 2.9; P = 0.39). CONCLUSION:
      Asymptomatic retinal cholesterol embolism is an important risk factor for
      cerebral infarction independent of commonly recognized vascular risk factors.

PMID- 7825760
TI  - Prolonged survival in chronic myelogenous leukemia after cytogenetic response to
      interferon-alpha therapy. The Leukemia Service.
AB  - OBJECTIVE: To determine whether a cytogenetic response after interferon-alpha
      therapy in patients with chronic myelogenous leukemia is independently associated
      with improved survival. DESIGN: Retrospective analysis. PATIENTS: 274 patients
      with a diagnosis of Philadelphia chromosome-positive chronic myelogenous leukemia
      in early chronic phase who were treated with interferon-alpha-based programs
      between 1982 and 1990. INTERVENTION: Therapy with daily subcutaneous interferon
      alpha given at 5 x 10(6) U/m2 body surface area (highest dose schedule allowed on
      studies) or the maximally tolerated lower-dose schedule. RESULTS: Overall, 219
      (80%) patients achieved a complete hematologic response and 104 (38%) achieved a
      major cytogenetic response (< 35% Philadelphia chromosome-positive cells).
      Estimated median survival was 89 months. Several pretreatment factors were
      associated with failure to achieve a major cytogenetic response and with worse
      survival. The existing prognostic models were generally predictive of which
      patients were likely to achieve a major cytogenetic response (P < or = 0.01) and
      of survival outcomes (P < or = 0.01). Multivariate analysis identified bone
      marrow basophilia (P < 0.01) and splenomegaly (P < 0.01) as independent poor
      prognostic factors for survival. Achievement of a major cytogenetic response,
      entered as a time-dependent variable while accounting for the other independent
      factors, was associated with improved survival (P < 0.001). Comparison of
      survival (dated from 12 months into therapy) with cytogenetic response at 12
      months showed that a cytogenetic response was associated with longer survival (P
      < 0.001). CONCLUSION: Achieving a cytogenetic response with interferon-alpha
      therapy in patients with chronic myelogenous leukemia was independently
      associated with improved survival when tested as a time-dependent variable in a
      multivariate analysis, and this association was confirmed by landmark analysis at
      12 months.

PMID- 7825762
TI  - Bleeding injuries in professional football: estimating the risk for HIV
      transmission.
AB  - OBJECTIVE: To determine the risk for bleeding injuries in professional football
      and to estimate the risk for transmission of the human immunodeficiency virus
      (HIV) through such injuries. DESIGN: A prospective, observational study.
      PARTICIPANTS: Professional football players from 11 teams of the National
      Football League were observed during 155 regular season games from September
      through December 1992. MEASUREMENTS: The frequencies of bleeding injuries were
      calculated in association with environmental and athletic factors. Using this
      information, HIV prevalence, and data on transmission of HIV in other
      circumstances, the risk for transmission of HIV during football games was
      estimated. RESULTS: 575 bleeding injuries (average, 3.7 per game for each team)
      involving 538 players (average, 3.5 players on each team per game) were observed.
      Approximately 88% of the bleeding injuries were abrasions; the remainder were
      lacerations. Bleeding injuries were markedly more frequent during games played on
      artificial surfaces, during games played in domed stadiums, and on teams with a
      final win/loss percentage of 0.500 or lower. Using data on the prevalence of HIV
      among college men and rates of HIV transmission in the health care setting, the
      risk for HIV transmission to each player was estimated to be less than 1 per 85
      million game contacts. CONCLUSIONS: Although injuries occur in professional
      football competitions, bleeding injuries, especially lacerations, occur
      infrequently. We estimate that the risk for HIV transmission during such
      competition is extremely remote. The role of artificial playing surfaces on the
      incidence or severity of bleeding injuries should be investigated.

PMID- 7825761
TI  - Classification of HIV infection and disease in women from Rwanda. Evaluation of
      the World Health Organization HIV staging system and recommended modifications.
AB  - OBJECTIVE: To develop a human immunodeficiency virus (HIV) staging system for sub
      Saharan Africa on the basis of an evaluation of the World Health Organization
      (WHO) system and predictors of mortality. DESIGN: Prospective cohort study with 4
      years of follow-up. SETTING: Kigali, Rwanda. PATIENTS: 412 HIV-infected women
      recruited from prenatal and pediatric clinics. MEASUREMENTS: Clinical signs and
      symptoms of HIV disease, laboratory assays (including complete blood count and
      erythrocyte sedimentation rate), and cumulative mortality. RESULTS: The WHO
      staging system includes a clinical and a laboratory axis. The clinical axis was
      revised by inclusion of oral candidiasis, chronic oral or genital ulcers, and
      pulmonary tuberculosis as "severe" disease (clinical stage IV); in addition, body
      mass index was substituted for weight loss in the definition for the wasting
      syndrome. The 36-month cumulative mortality was 7% for women in modified clinical
      stage I ("asymptomatic"), 15% for those in stage II, 19% for those in stage III,
      and 36% for those in stage IV (P < 0.001). The laboratory axis was revised by
      replacing lymphocyte count with hematocrit and erythrocyte sedimentation rate.
      The 36-month mortality was 10% for women in modified stage A ("normal" laboratory
      results) and 33% for those in stage B (erythrocyte sedimentation rate > 65 mm/h
      or hematocrit < 0.38) (P < 0.001). A single staging system combining clinical and
      laboratory criteria is proposed, with a 36-month mortality of 7% for women in
      combined stage I, 10% for those in stage II, 29% for those in stage III, and 62%
      for those in stage IV (P < 0.001). CONCLUSIONS: On the basis of this analysis, a
      staging system relevant for sub-Saharan Africa is proposed that reflects the
      range of HIV-related outcomes, has strong prognostic significance, includes
      inexpensive and available laboratory tests, and can be used by both clinicians
      and researchers.

PMID- 7825763
TI  - Living related-donor liver transplantation from adult to adult for primary
      biliary cirrhosis.

PMID- 7825764
TI  - Measuring and improving physician compliance with clinical practice guidelines. A
      controlled interventional trial.
AB  - OBJECTIVE: To determine factors that may lead physicians not to comply with
      clinical practice guidelines. DESIGN: Retrospective analysis of patients whose
      physicians were not compliant with discharge recommendations from a prospective,
      controlled interventional trial of a guideline to reduce hospital length of stay
      for patients admitted for chest pain. SETTING: A large community teaching
      hospital. PARTICIPANTS: Patients admitted with chest pain who were not discharged
      according to a practice guideline. RESULTS: 79 (34%) of 230 patients with chest
      pain classified as being at low risk by concurrent or retrospective review were
      not discharged by day 3 (the guideline recommendation). Of these 79 patients, 33
      (42%) were misclassified at concurrent review (10 were falsely classified as
      being at high risk and 23 were falsely classified as being at low risk). Of 46
      correctly classified patients, 11 (14%) were classified as having noncompliant
      physicians because of health care system inefficiencies. The status of 7 (9%)
      patients was changed to high risk between initial classification and potential
      discharge. For 15 patients (19%), no obvious reason for delayed discharge was
      found, but they had a higher severity of illness than did low-risk patients
      discharged according to the guideline as measured by mean time-insensitive
      predictive instrument scores (41.3% +/- [SD] 14.1% compared with 31.5% +/- 14.3%;
      P = 0.017). In 13 patients (16%), physicians refused to follow the guideline
      recommendations. CONCLUSIONS: In measuring and attempting to improve physician
      compliance with a length-of-stay guideline, physician refusal accounts for a
      small percentage (16%) of noncompliance. Implementation issues, health care
      system inefficiency, and severity of illness were the predominant reasons why
      physicians did not comply with guidelines. Our study further supports the
      principle that clinical practice guidelines should complement rather than be a
      substitute for physician judgment.

PMID- 7825765
TI  - Transmission of blood-borne pathogens during sports: risk and prevention.
AB  - Publicity about human immunodeficiency virus (HIV) infection in athletes has
      focused attention on the potential for transmission of blood-borne pathogens
      during sports and athletic competitions. Existing information suggests that the
      potential risk for such transmission is extremely low and that the principal
      risks athletes have for acquiring HIV and hepatitis B virus are related to off
      the-field activities. Therefore, efforts to prevent transmission of blood-borne
      pathogens among athletes should emphasize prevention in off-the-field settings.
      We summarize technical and other information about this issue, and provide
      recommendations for the education of sports participants, for infection control
      in athletic settings, and for training of coaches and officials.

PMID- 7825766
TI  - Postprandial hypotension: epidemiology, pathophysiology, and clinical management.
AB  - OBJECTIVE: To show the clinical relevance of postprandial hypotension and to
      review its pathophysiology and management. DATA SOURCES: Articles on postprandial
      hypotension were identified through MEDLINE and bibliographies of relevant
      articles. STUDY SELECTION: All articles and case reports describing meal-related
      hypotension in the elderly and in patients with autonomic failure. DATA
      SYNTHESIS: Postprandial hypotension, defined as a decrease in systolic blood
      pressure of 20 mm Hg or more, may result in syncope, falls, dizziness, weakness,
      angina pectoris, and stroke. Postprandial hypotension is distinct from and
      probably more common than orthostatic hypotension. Because meal-related
      hypotension is particularly common in older hypertensive patients, it has
      important implications for the evaluation and management of hypertension. The
      mechanism of postprandial hypotension is not fully understood. Possible
      contributors include inadequate sympathetic nervous system compensation for meal
      induced splanchnic blood pooling; impairments in baroreflex function; inadequate
      postprandial increases in cardiac output; and impaired peripheral
      vasoconstriction, insulin-induced vasodilation, and release of vasodilatory
      gastrointestinal peptides. Although caffeine is often recommended as treatment
      for postprandial hypotension, available data do not support its use. Octreotide,
      a somatostatin analog, has been shown to be effective, but it is expensive and
      must be given parenterally. CONCLUSION: All physicians caring for elderly
      patients should be aware of the hypotensive effects of food intake and should
      consider postprandial hypotension in the evaluation of syncope, falls, dizziness,
      and other cerebral ischemic symptoms.

PMID- 7825767
TI  - Functional magnetic resonance imaging of the brain.
AB  - This conference reviewed the potential scope of application of recently developed
      techniques for functional magnetic resonance imaging (fMRI) of the brain. The
      most successful technique is based on the sensitivity of magnetic resonance
      imaging (MRI) to magnetic effects caused by the modulation of the oxygenation
      state of hemoglobin, which is induced by local variations in blood flow during
      task activation. Typically, the MRI signal increases by a few percentage points
      during brain activation because blood flow and oxygen supply sharply increase.
      Brain activation images with excellent combined spatial and temporal resolution
      have been obtained noninvasively using visual, sensorimotor, or auditory stimuli,
      or during higher-order cognitive processes such as language or mental imagery.
      Although sensitive to misregistration artifacts and macroscopic vessels, MRI
      permits both the direct correlation of function with underlying anatomy and
      repeated studies on the same person. It may become the method of choice for
      studies of mental and cognitive processes, presurgical mapping, monitoring
      recovery from stroke or head injuries, exploration of seizure disorders, or
      monitoring the effects of neuropharmaceuticals.

PMID- 7825768
TI  - The cardiopulmonary resuscitation-not-indicated order: futility revisited.
AB  - This paper reviews the advent of unilateral do-not-resuscitate orders. Unilateral
      do-not-resuscitate policies presume that cardiopulmonary resuscitation is a
      medical therapy and that physicians have no obligation to undertake a medical
      therapy that does not offer achievable and appropriate goals. Four do-not
      resuscitate policies from U.S. hospitals and some of the significant published
      proposals are reviewed. We conclude that anything other than a physiologic
      definition of futility is indefensible because of imposed value judgments,
      imprecise definitions of quantitative and qualitative futility, inexact data,
      lack of certitude of economic benefit, and the role of autonomy for the patient
      and physician.

PMID- 7825769
TI  - Immigrants and health care: mounting problems.

PMID- 7825770
TI  - Preventing firearm violence: a public health imperative. American College of
      Physicians.

PMID- 7825771
TI  - Atovaquone for Pneumocystis carinii pneumonia.

PMID- 7825772
TI  - Atovaquone for Pneumocystis carinii pneumonia.

PMID- 7825773
TI  - Antiendotoxin antibodies.

PMID- 7825774
TI  - Aseptic meningitis and intravenous immunoglobulin therapy.

PMID- 7825775
TI  - Aseptic meningitis and intravenous immunoglobulin therapy.

PMID- 7825776
TI  - Primary subcutaneous abscess caused by Rhodococcus equi.

PMID- 7825777
TI  - [Health psychology: a new approach in the understanding of health and disease].
AB  - This article aims to present health psychology, a new discipline which recently
      appeared in the U.S.A., then in Europe and finally in France. It is defined as
      the study of interactions between psychological, sociological and biological
      factors which are influential in the onset, course and prognosis of somatic
      diseases. Health psychology insists on the moderating role of processual
      variables in the understanding of stress-distress relationship: perceived stress,
      coping, perceived control, social support. The most valid assessment methods of
      these constructs are also presented. Its application aims to promote healthy life
      styles, prevention of diseases and the improvement of the management and care of
      patients.

PMID- 7825778
TI  - [Health psychology, medical psychology, psychosomatic medicine and liaison
      psychiatry].
AB  - Health psychology is a new discipline which introduces transactional conceptions
      and biopsychosocial integrative models of health and disease. Its fields of
      research overlap the traditional domain of psychosomatic medicine (study and
      treatment of the mind--conscious or unconscious--of organic patients), and also,
      partially, the domain of psychological medicine (which in France is focused on
      the psychology of the practitioner and the patient-doctor relationship),
      behavioral medicine and liaison psychiatry (which is the use of modern diagnosis
      and treatment of psychiatry proper to medical patients). Rather than a potential
      competition, one must see a challenge and an opportunity for renewal of
      psychiatry in the field of medicine as well as collaborative perspectives. Health
      psychology uses new stringent methodology and instruments for research
      (dimensions) evolving from scientific psychology. Brief and critical analysis of
      this new discipline.

PMID- 7825779
TI  - [The current status of post-traumatic stress syndrome in children].
AB  - The Disorder of Post-Traumatic Stress belongs to the category of Anxiety
      Disorders. It consists of a group of symptoms which develop, with a variable
      period of latency, after an event which is outside the range of usual human
      experience and generally generates a feeling of intense fear in the child. The
      typical characteristic resulting clinical picture resembles that observed in
      adults (reexperiencing the traumatic event, persistent avoidance of stimuli
      associated with the trauma, neuro-vegetative hyperactivity) and is molded by the
      child's development. The long-term outcome of this disorder remains unclear; but
      it appears to be most favorable in children than in adults. Several factors could
      either "predispose" the child to this disorder or "protect" him (her) from it:
      the degree and duration of exposure to the traumatic event, the nature of the
      trauma, the presence of preexisting psychiatric conditions, the level of
      cognitive development and gender of the child, and the presence or absence of
      family support. Those therapeutic approaches which have demonstrated their
      usefulness in adults (group therapy, psychodynamic individual therapy...) remain
      to be applied to children and evaluated in this age group.

PMID- 7825780
TI  - [Revision of the International Classification of Handicaps].

PMID- 7825781
TI  - [The obligation to cure mental patients in Greco-Roman antiquity].

PMID- 7825782
TI  - [Psychopathology and travel: psychiatric patient repatriation].

PMID- 7825783
TI  - [The "inside-outside" caused by thoracic effraction for the treatment of
      mediastinitis].

PMID- 7825784
TI  - [Eating disorders and insulin dependent diabetes: a current issue].
AB  - Association between insulin-dependent diabetes mellitus (IDDM) and eating
      disorders (anorexia nervosa, bulimia nervosa) was recently described. We have
      reviewed the systematic studies that were conducted on this topic, particularly
      for prevalence of anorexia nervosa and bulimia nervosa and their relations with
      metabolic control (HBA1C) and somatic complications of insulin-dependent diabetes
      mellitus. We have discussed methodological problems of these studies and
      etiopathogenic aspects of eating disorders in this somatic disease.

PMID- 7825785
TI  - [Outline of Nahua ethnopsychiatry].
AB  - In this paper we will show some historical and cultural aspects of the Aztec's
      medicine and cosmology at the XVI century. The Aztecs or Nahuas used to believe
      in different kinds of anemic entities, the most important ones being the tonalli,
      the ihiyotl and the teyolia. At the time the word tonalli meant, simultaneously,
      the particular "genius" of everyone, good fortune and the "star" or destiny. The
      tonalli's loss was a cause of illness and dead and it could be provoked by some
      physical violent acts or by sudden feelings of fright. The most frequent
      expression of this sickness was named tetonalcahualiztli. The hispanic
      designation of this problem is susto. The Nahuas used many kind of psychological
      proceedings in order to alleviate anguish and to treat mental troubles. Illness
      was considered by nahuas practitioners as the balance's loss of the organism, not
      only of its own components but also of its relationship with the world.

PMID- 7825786
TI  - [Patient, family, nurses and intensive care unit: review of the literature and
      state of a practice "in the field"].
AB  - An increasing interest in psychological and interactional aspects of intensive
      care unit stay is found in the recent literature. On one hand, seriousness and
      acuteness of the pathology, on the other hand, environment specificity as well as
      their respective consequences result in the fact that the ICU is a peculiar
      context for the patient and his family. The patient experiences a stressful event
      which probably differs from the one experienced in other types of wards. The
      family and its needs during this critical period are the focus of an increasing
      number of studies. A corresponding occupational stress for the caregivers is now
      widely acknowledged.

PMID- 7825787
TI  - [Health and Human Rights. Proceedings of a meeting. Prague, 12-14 May 1994].

PMID- 7825788
TI  - [Human rights and the birth of psychiatry. From natural rights to treatment of
      the insane].

PMID- 7825789
TI  - [Ambiguity and paradox: silence obligated by law].

PMID- 7825790
TI  - [The representation of the mental patient in motion pictures].
AB  - By the examples of 80 movies from different countries, the study describes the
      representation of mental patients, in the films. They are shown as victims of
      family and society. And the psychiatric hospital is never shown as therapeutic,
      but only used for keeping away, and bringing back the stray sheep to the social
      fold.

PMID- 7825791
TI  - [AIDS: ethical drift].
AB  - AIDS is not merely a new viral disease, or an unprecedented variety of acquired
      immune deficiency. It is an STD equally transmitted by blood and birth, it has
      for the last eleven years, baffled all the assault attempted by the most
      competent researchers, it is lethal in the vas majority of cases, it has reached
      a planetary dimension. Its prevention interferes as well with more than one
      religion's prescriptions and will undoubtedly interfere with sexual fulfillment.
      Finally, it reminds us that what we call ethics is fragile, that it is actually
      based on an agreement and that it can be drastically modified if a majority of
      citizens are under threat.

PMID- 7825792
TI  - [Biological tests in the hospital and human rights: concerning HIV serology].
AB  - The spreading of a new pathology, highly involved in the medical and
      psychological fields, A.I.D.S., combined with the present biological achievements
      make the different hospital services face many ethical problems. Following the
      various stages in the making of H.I.V. serologies, the authors intend to describe
      behaviours, practicing, and new regulations which allow the patients' rights to
      be held in greater respect.

PMID- 7825793
TI  - [Fractures from falls in elderly patients: are they neuropsychiatric
      emergencies?].
AB  - To identify a possible link between mental impairment and spontaneous fall
      related fractures, we studied two groups of elderly hospitalized patients for
      physical and cognitive status. The study population consisted of 120 patients
      admitted for post-surgical rehabilitation after fall-related fractures (FRF). The
      patients were living at home when the accident occurred. The mean age was 81.0
      years; 110 women, mean age 81.2 +/- 8.1; 10 men, mean age 82.8 +/- 8.5 years).
      The control group consisted of 81 patients hospitalized for somatic conditions
      who had never had falls or fractures (46 women and 35 men, mean age 79.4 +/- 5.7
      years). The following cognitive tests were used: Folstein's MMSE, Benton's visual
      recall, and the Rey figure with both subtests (copy: RC; and recall: RM). In the
      study population (95%) 114 patients had previously fallen and 44 (38%) had had
      fractures, 65% had cardiovascular disease, compared to 6% of the controls. The
      respective mean psychometric scores for each test in the study and control
      population were as follows: MMSE: 18.92 +/- 6.45 vs 24.2 +/- 3.2 (normal value >
      25); P = 4.5 x 10(-8). Benton: 11.03 +/- 4.91 vs 15.69 +/- 3.2 (normal value >
      25); P = 2.3 x 10(-8). RC: 14.84 +/- 9.9 vs 25 +/- 7.6 (normal value > 30); P =
      4.5 x 10(-8). RM: 4.55 +/- 4.5 vs 9.04 +/- 5.7 (normal value > 22); P = 2.17 x
      10(-8). Despite these patient's apparently normal social facade, they had a far
      mode marked and significated mental deterioration than the controls.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7825794
TI  - [Treating psychic traumas: a psychiatric emergency].
AB  - Interest for the psychopathological field of trauma has experienced a revival
      over the last fifteen years. Early and active treatment of victims is necessary
      to attenuate the psychopathological consequences of trauma. However, emergency
      psychiatry still rarely places a high value on it. This paper presents a case
      which contains in itself many aspects of psychological responses to
      psychologically traumatizing events. Trauma induced in this case, in particular,
      Dissociative Disorders (including a Dissociative Fugue), a Post-Traumatic Stress
      Disorder, Somatoform Disorders and Phobic Disorders. This case gives us the
      opportunity to situate the psychiatric emergency--"psychological trauma"--and to
      illustrate our talk with regard to the principles of mid-term and emergency
      treatment of victims.

PMID- 7825795
TI  - Neuroimmunomodulation. From phenomenology to molecular evidence.

PMID- 7825796
TI  - Prolactin-mediated cellular interactions in the thymus.

PMID- 7825797
TI  - In vitro studies on the thymus-pituitary axis in young and old rats.

PMID- 7825798
TI  - Thymic endocrine function in neuroendocrine human diseases.

PMID- 7825799
TI  - Differential influence of a thymic extract on alpha- and beta-adrenoceptors of
      mouse brain cortex.

PMID- 7825800
TI  - The role of calcitonin gene-related peptide in the mouse thymus revisited.
AB  - Calcitonin gene-related peptide has been identified by immunocytochemistry within
      the thymus of fetal through aged adult mice. Calcitonin gene-related peptide
      positive nerves are observed from embryonic day 17 throughout the lifespan of the
      mouse. A sparse cell population positive for CGRP is first observed during the
      late embryonic period at the corticomedullary boundary and the medulla, and it
      becomes more densely distributed in this region in the adult. In the thymus of
      the aged mouse the number of CGRP-positive cells diminishes. Pharmacologic
      studies demonstrated that fresh thymocytes display a receptor Kd for CGRP of 1.17
      +/- 0.06 x 10(-10)M and a Bmax of 12.7 +/- 4.7 fmol/mg protein. Functional
      studies indicate that CGRP is a potent inhibitor of mitogen and antigen
      stimulated proliferation of T cells and that it inhibits IL-2 production in
      cloned splenic T cells. Recent studies suggest that endogenous CGRP may serve as
      a natural inhibitor of inappropriate induction of mature, antigen-sensitive cells
      in the thymus as well as play a role in thymocyte education. These findings are
      discussed in terms of the distribution of CGRP cells and nerve terminals within
      the thymus and their relationship to positive and negative selection of the T
      cell repertoire.

PMID- 7825801
TI  - Antiinflammatory effects of the neuropeptide alpha-MSH in acute, chronic, and
      systemic inflammation.

PMID- 7825802
TI  - Cytokine antagonists in infectious and inflammatory disorders.

PMID- 7825803
TI  - Endotoxins, cytokines, and neuroimmune networks with special reference to HIV
      infection.

PMID- 7825804
TI  - Prolonged asymptomatic states in HIV-seropositive persons with fewer than 50 CD4+
      T cells per MM3. Psychoneuroimmunologic findings.

PMID- 7825805
TI  - Pineal-opioid system interactions in the control of immunoinflammatory responses.
AB  - Several studies have demonstrated involvement of the pineal gland in the
      regulation of neuropeptide secretion and activity. In particular, the existence
      of links between the pineal gland and the brain opioid system has been
      documented. Both opioid peptides and melatonin (MLT), the most investigated
      pineal hormone, play an important role in neuromodulation of the immunity.
      Moreover, the immune effects of MLT are mediated by endogenous opioid peptides,
      which may be produced by both the endocrine system and the immune cells. In
      addition, the immune dysfunctions that characterize some human diseases, such as
      cancer, depend not only on the immune system per se, but also at least in part,
      on altered secretion of immunomodulating neurohormones, including MLT and opioid
      peptides. Therefore, the exogenous administration of neurohormones could
      potentially improve the immune status in humans. The present study evaluates the
      effects of MLT on changes in the number of T lymphocytes, natural killer cells,
      and eosinophils induced by exogenous administration of interleukin-2 (IL-2).
      Macrophage activity was also evaluated by determining serum levels of its
      specific marker, neopterin. The study was performed in 90 patients with advanced
      solid neoplasms, who received IL-2 at a dose of 3 million IU/day subcutaneously
      for 6 days a week for 4 weeks plus MLT at a daily dose of 40 mg. Both drugs were
      given in the evening. The results were compared to those in 40 cancer patients
      treated with IL-2 alone. The mean increase in T lymphocytes, natural killer
      cells, and eosinophils was significantly higher in patients treated with IL-2
      plus MLT than in those who received IL-2 alone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7825806
TI  - Correlation between estradiol serum levels and NK cell activity in endometriosis.

PMID- 7825807
TI  - Stress, distress, and immunity.
AB  - Since psychoimmunology is now 10 to 20 years of age, it seems appropriate to
      expect a certain maturity in the field. It seems reasonably well established that
      there really is neuroimmunomodulation. The biological and medical importance of
      this is the possible influence of psychological factors on immune competence.
      Inasmuch as it is reasonably well established that psychological factors do have
      such an influence, the field must now endeavor to establish how important this
      influence is. It no longer suffices to show that some sort of stressor has some
      sort of action on some part of the immune cascade of responses. "Stressors" do
      not act indiscriminately; they are filtered and interpreted by the brain
      following psychological principles that again are reasonably well known. The
      distinction between "stress" and "distress" is important for the health
      consequences of how and with what success an individual is handling a stressful
      situation. Concepts such as coping, control, helplessness, and hopelessness are
      required to understand how immune responses are influenced by the brain and to
      establish the extent to which these mechanisms have clinical validity in man and
      animals.

PMID- 7825808
TI  - What is stress? How does it correlate with the immune system?

PMID- 7825809
TI  - Neuroendocrine axis and behavioral stress.

PMID- 7825810
TI  - Immune system and the hypothalamus-pituitary-adrenal axis. Common words for a
      single language.

PMID- 7825811
TI  - Rotational stress reduces the effectiveness of antitumor drugs in mice.

PMID- 7825812
TI  - Influence of pain stimulation on interleukin-2 production in mice.
AB  - We previously demonstrated that plaque-forming cell (PFC) production in the
      spleen of mice immunized with sheep red blood cells (SRBC) was enhanced by pain
      stimulation. This phenomenon was due to activation of antigen nonspecific L3T4
      /Lyt-2- T lymphocytes (double-negative T cells) by the beta-adrenergic action of
      endogenous catecholamines released from the adrenal gland after pain stimulation.
      Further study also demonstrated that interleukin-2 (IL-2) production of spleen
      cells was enhanced in mice by pain stimulation. In this study spleen cells of
      BALB/c mice were cultured with Con A and SRBC, respectively, and the IL-2 level
      was measured by incorporation of 3H-thymidine into CTLL-2 cells during culture
      for 24 hours. Interleukin-2 production of spleen cells from mice given pain
      stimulation was significantly increased compared with spleen cells of normal
      mice. The IL-2 production of spleen cells of normal mice was also markedly
      enhanced by the mixed culture with spleen cells from pain-stimulated mice.
      Enhancement of IL-2 production in the spleen cells of mice given pain stimulation
      did not occur with anti-Thy-1.2 antibody and complement treatment, but production
      was maintained by treatment with anti-L3T4 antibody and complement. These data
      suggest that the enhanced production of IL-2 in mice given pain stimulation
      resulted from the activation of L3T4- T cells by endogenous catecholamines
      released from the adrenal gland after pain stimulation. It can be assumed that
      activated L3T4- T cells interact with antigen-specific L3T4+ T cells and lead to
      enhanced IL-2 production.

PMID- 7825813
TI  - Genetic differences in immunomodulation, behavior, and stress-induced organ
      lesions.

PMID- 7825814
TI  - Hypothalamic-pituitary-adrenal axis in neuropsychiatric disorders.

PMID- 7825815
TI  - Influence of brain and behavioral lateralization in brain. Monoaminergic,
      neuroendocrine, and immune stress responses.

PMID- 7825816
TI  - Immune enhancement by conditioning of senescent mice. Comparison of old and young
      mice in learning ability and in ability to increase natural killer cell activity
      and other host defense reactions in response to a conditioned stimulus.
AB  - It has been clearly demonstrated that immune responses may be conditioned in a
      manner similar to that of the classical Pavlovian experiments. Evidence of
      impaired immune function in aging has raised the question of whether
      psychological conditioning of an immune response can also be effective in old
      age. The knowledge that aged mice have decreased spleen cell natural killer (NK)
      activity and that NK cytotoxicity, at least in young mice, can be psychologically
      conditioned led us to explore in old mice the possibility of conditioning the
      response of NK cell activity using the odor of camphor as the conditioned
      stimulus (CS) and the injection of Poly I:C as the unconditioned stimulus (US).
      Young and old male mice were divided into five and six groups, respectively. They
      received the CS and/or the US in association (conditioning) trials (sessions 1
      9). Mice were exposed to the camphor odor alone at 72 hours after the final
      association trial to observe the conditioning phenomenon (session 10). The group
      conditioned with Poly I:C and camphor and receiving the CS at session 10 showed
      statistically significant increases in spleen cell NK activity over those of the
      control groups that did not receive the CS treatment at session 10 (2.6- and 4.0
      fold increase in young and old, respectively). Treatment with camphor odor alone
      had no effect on boosting NK cell activity. These findings demonstrate the
      possibility of conditioning immune responses in old age, offering a valuable tool
      for attenuating age-related immune deterioration in various species, including
      the human. In addition, these results again confirm highly significant immune
      enhancement by classical conditioning and extend previous findings from female
      mice to males as well.

PMID- 7825817
TI  - Shared ligands and receptors as a molecular mechanism for communication between
      the immune and neuroendocrine systems.

PMID- 7825818
TI  - Regulation of cytokine production in aging mice.

PMID- 7825819
TI  - Expression of human heat-shock protein 70 antigens and gamma/delta T-cell
      receptor antigens in human central nervous tissue.
AB  - The human gamma delta T cell receptor is normally expressed on lymphoid tissue.
      Because expression of different molecules of the T-cell system has been described
      on human brain cells, we examined the expression of T-cell receptor gamma delta
      antigens with a panel of various anti-gamma/delta TCR mAbs using
      immunohistochemistry on different regions of frozen human postmortem tissue of
      five different brains. We found expression of gamma/delta TCR antigens on brain
      tissue in different regions of the brain, probably on neurons. Using mAbs against
      the 70-kd human heat-shock-protein (hsp 70), immunohistochemistry showed staining
      of microglia. A polymerase chain reaction analysis using a highly sensitive
      primer sequence against the constant region delta sequence supports the notion
      that the gamma/delta TCR is expressed in human brain; however, the sequence
      cannot be assigned to a specific tissue with this method. Both heat shock
      proteins and the gamma/delta TCR seem to be involved in autoimmune processes, and
      their expression on colocalizing structures in human CNS may play a role in
      triggering neuropsychiatric autoimmune disorders.

PMID- 7825820
TI  - Dopamine D1 receptors in the amygdala enhance the immune response in the rat.
AB  - Indirect evidence suggests that dopamine within the brain may participate in the
      regulation of immune responses in both man and rodents. The aim of the present
      study was to investigate the possible role played by the specific dopamine D1
      receptor subtype within the central amygdala in the modulation of immunity.
      Mitogen responsiveness of splenocytes and NK cell activity were measured in rats
      following local microinfusion of SKF 38393, a specific dopamine D1 receptor
      agonist. Microinfusion of SKF 38393 (100 nmol) within the central amygdala
      increased the proliferative response of splenocytes to Con A, whereas it did not
      modify the proliferative response of splenocytes to LPS or NK cell activity. The
      effects of SKF 38393 were prevented by prior systemic administration of SCH 23390
      (0.3 mg/kg ip), a specific D1 receptor antagonist. These results indicate that
      activation of dopamine D1 receptors within the central amygdala induced selective
      stimulation of mitogen responsiveness of splenocytes and suggest that specific
      activation of dopamine neurotransmission within selected areas of the limbic
      system may produce immunoenhancing effects. These findings further confirm the
      immunomodulatory role played by dopaminergic mechanisms in the brain.

PMID- 7825821
TI  - Interleukin-1 receptors in brain and pituitary. Characterization and modulation
      during infection and stress.

PMID- 7825823
TI  - Melatonin treatment mimics pineal graft action in regulating brain cortex
      adrenoceptors in aging mice.

PMID- 7825822
TI  - Widespread activation and consequences of interleukin-1 in the brain.
AB  - The results described herein indicate that elevation of IL-1 in rat brain, either
      by infusion of IL-1 into the brain or by stimulation of release of endogenous IL
      1 in the brain by LPS, rapidly suppresses a variety of immune responses measured
      in peripheral lymphocytes. This effect can be blocked by infusion of alpha-MSH
      into brain, an attribute that was used to indicate that the effects of LPS
      infusion occurred by stimulation of endogenous IL-1 and not some other influence
      of LPS. That suppression of cellular immune responses indeed describes the
      consequences of elevating IL-1 in brain was shown by determining the time course
      of effects and thereby demonstrating that rebound enhancement of cellular immune
      responses did not occur after either IL-1 or LPS. Studies that examined the
      mechanisms by which brain IL-1 affects immune responses indicated that IL-1
      influences peripheral lymphocytes by stimulation of CRF in the central nervous
      system and that CRF in turn causes suppression of cellular immune responses
      through activation of both the pituitary-adrenal axis and the autonomic nervous
      system. These findings have also been observed in another laboratory. Moreover,
      Brown et al. have shown that IL-1 in brain suppresses macrophage function in
      addition to the suppression of lymphocyte functions described herein. The
      physiologic significance of IL-1 actions in the brain on immune responses remains
      to be determined, but the demonstration that this cytokine influences immune
      processes by acting in brain opens for study another means by which brain and
      immune system interact.

PMID- 7825824
TI  - Biology of nitric oxide in neuroimmunoregulation.

PMID- 7825825
TI  - The pineal gland as ontogenetic scanner of reproduction, immunity, and aging. The
      aging clock.

PMID- 7825826
TI  - Role of cytokines in the endocrine system.

PMID- 7825827
TI  - Neuroimmunomodulation in the gastrointestinal tract.

PMID- 7825828
TI  - Regulation of NK cell lymphokine responsiveness by pituitary-thyroid hormones
      during ontogeny in mice. Suggestion for a sequential neuroendocrine-immune cross
      talk.

PMID- 7825829
TI  - Problems and perspectives in the approach to neuroendocrineimmunomodulation
      studies.

PMID- 7825830
TI  - Cryptocrine signaling in the thymus network. Implications for central T-cell
      tolerance of neuroendocrine functions.

PMID- 7825831
TI  - Regulation of prostaglandin E2 production in P388D1 macrophage-like cells.

PMID- 7825832
TI  - Activation of mitogen-activated protein kinase and arachidonate release via two G
      protein-coupled receptors expressed in the rat hippocampus.
AB  - Platelet-activating factor and somatostatin receptors, two G protein-coupled
      receptors expressed in the rat hippocampus, were analyzed for the downstream
      signaling pathways in Chinese hamster ovary cells stably expressing each
      receptor. Ligand stimulation to each CHO cell line induced (1) inhibition of
      forskolin-induced accumulation of cAMP, (2) arachidonate release, and (3)
      activation of mitogen-activated protein kinase and MAP kinase kinase. In
      contrast, inositol phosphate breakdown was seen only in the PAF-stimulated CHO
      cells. The induction of these signals accompanied no detectable Ras activation.
      Suppression of the signals by pertussis toxin was almost complete for the
      somatostatin receptor but partial for the PAF receptor, suggesting that the
      somatostatin receptor couples only with PTX-sensitive G protein, while the PAF
      receptor couples with both PTX-sensitive and -insensitive G proteins. A model of
      G protein-mediated signaling pathways was proposed in which the signals from Gi
      and those from Gq converge at MAP kinase kinase and lead to arachidonate release.
      The present system using CHO cells is useful for analyzing signaling pathways
      from G proteins to MAP kinase kinase and will thereby provide clues for
      understanding the mechanisms underlying the physiological and pathological events
      mediated by PAF, somatostatin, and other G protein-coupled receptors in the
      central nervous system and other tissues.

PMID- 7825833
TI  - Prostanoid receptors. Structure, function, and distribution.

PMID- 7825834
TI  - Cyclooxygenase-dependent formation of the isoprostane 8-epi prostaglandin F2
      alpha.

PMID- 7825835
TI  - Diverse mechanisms of specificity of human receptors for eicosanoids.

PMID- 7825836
TI  - Leukotriene D4-induced signal transduction.
AB  - In a human epithelial cell line LTD4 induces a calcium signal that is dependent
      on both intracellular mobilization and influx of calcium. This calcium signal is
      generated via the activation of dual G protein pathways. Whereas the
      intracellular mobilization of calcium is regulated by a pertussis toxin
      insensitive G protein, the subsequent influx of calcium is regulated by a
      pertussis toxin-sensitive G protein. Furthermore, a LTD4-induced cellular
      elevation of cAMP also participates in the regulation of this calcium signal. The
      increase in cAMP is directly related to the LTD4-induced influx of calcium,
      perhaps by an activation of protein kinase A and a subsequent phosphorylation of
      a plasma membrane channel. This model of the LTD4-induced signaling pathway in
      epithelial cells is outlined in Figure 2.

PMID- 7825837
TI  - Prostaglandin J2 and related compounds. Mode of action in G1 arrest and
      preclinical results.

PMID- 7825838
TI  - Cell-cell interactions in lipoxin generation and characterization of lipoxin A4
      receptors.

PMID- 7825839
TI  - Cytokine regulation of eicosanoid generation.

PMID- 7825840
TI  - Priming of monocytes with interferon-gamma is associated with up-regulation of
      expression of the receptor for platelet-activating factor.

PMID- 7825841
TI  - Interactions between histamine and leukotrienes in the microcirculation. Aspects
      of relevance to acute allergic inflammation.

PMID- 7825842
TI  - 12-Lipoxygenase, 12(S)-HETE, and cancer metastasis.

PMID- 7825843
TI  - Lipoxygenase products in normal and diseased glomeruli.
AB  - Figure 4 is a schematic summary of current evidence implicating products of the
      15-lipoxygenase pathway of arachidonic acid metabolism, principally 15-S-HETE and
      LXA4, as endogenous antagonists for the proinflammatory actions of leukotrienes.
      Here, we have presented evidence for the pathophysiologic relevance of
      leukotrienes in glomerular immune injury and the emerging data on the
      multifaceted counterinflammatory actions of 15-lipoxygenase products as they
      relate specifically to the renal glomerulus. Clearly, these concepts are of a
      broader nature and would be expected to pertain to inflammatory reactions in
      general, be they in the glomerulus, the renal interstitium, or in extrarenal
      sites. The extent to which these early observations can be exploited to design
      strategies for the control of self-destructive inflammatory reactions in the
      kidney and elsewhere will be determined by future studies. Imaginative design of
      molecular tools for the manipulation of these enzyme systems in vivo, however,
      represents a potentially fruitful area of research towards the attainment of a
      highly worthwhile goal: the cure of glomerulonephritis.

PMID- 7825844
TI  - Eicosanoid biosynthesis and metabolism in myeloproliferative disorders.

PMID- 7825845
TI  - Isoprostanes. Novel markers of endogenous lipid peroxidation and potential
      mediators of oxidant injury.
AB  - It was recently discovered that a series of structurally unique prostaglandin F2
      like compounds (F2-isoprostanes) capable of exerting potent biological activity
      are produced in vivo in humans by a noncyclooxygenase mechanism involving free
      radical catalyzed peroxidation of arachidonic acid. Considerable evidence has
      been obtained suggesting that quantification of F2-isoprostanes represents an
      important advance in our ability to assess oxidant status in vivo in humans. This
      has allowed us to implicate oxidant stress in the pathogenesis of human disease
      for example, the hepatorenal syndrome. In addition to the F2-isoprostanes, we
      recently discovered that E-ring and D-ring isoprostanes are also produced in
      abundance in vivo by rearrangement of the isoprostane endoperoxide intermediates.
      We have also been able to demonstrate that one of the E2-isoprostanes, 8-epi
      PGE2, is a potent renal vasoconstrictor in the rat. Insights into factors that
      may influence the formation of E2/D2-isoprostanes relative to F2-isoprostanes
      should be important in advancing our understanding of the biological consequences
      of the formation of isoprostanes in vivo.

PMID- 7825846
TI  - Leukotrienes mediate delayed airway effects of 15-HETE.

PMID- 7825847
TI  - Novel transformations of HPETEs by cytochrome P450s.

PMID- 7825848
TI  - Eicosanoids and asthma.

PMID- 7825849
TI  - Stereoselective metabolism of the 5-lipoxygenase inhibitor A-78773.
AB  - Based on the knowledge that glucuronidation was a major route of metabolism of
      the N-hydroxyurea class of 5-lipoxygenase inhibitors, a simple in vitro
      glucuronidation assay was established using liver microsomes from various
      species, including man. Compounds that were potent inhibitors of 5-LO and showed
      a reduced metabolic liability in vitro were then characterized more extensively
      in experimental animals. This prudent usage of in vitro glucuronidation proved to
      be highly efficient and was indispensable in the identification of A-78773, a
      potent new long-acting 5-LO inhibitor. Further studies with liver microsomes
      revealed that glucuronidation of A-78773 was stereoselective and that the R(+)
      enantiomer was considerably more resistant to conjugation than the S(-)
      stereoisomer. Pharmacokinetic studies in experimental animals and humans
      confirmed the greater metabolic stability of the R(+) enantiomer. A single 400-mg
      oral dose of A-78773 inhibited ex vivo leukotriene biosynthesis for more than 24
      hours. Since 78% of the drug plasma AUC following A-78773 administration was
      accounted for by the R(+) enantiomer, it is reasonable to assume that the
      majority of the leukotriene inhibition caused by the racemate is attributable to
      the R(+) enantiomer, A-79175, particularly at the later times. The equivalent 5
      lipoxygenase inhibitory potency coupled with the superior pharmacokinetic profile
      of the R(+) enantiomer, A79175, compared to the S(-) enantiomer, A-79176,
      indicate that the development of this compound may be preferable to the racemate
      A-78773.

PMID- 7825851
TI  - Preclinical exploration of the potential antiinflammatory properties of the
      peptide leukotriene antagonist ICI 204,219 (Accolate).

PMID- 7825850
TI  - Studies of the combination of Ro 24-5913, a peptidoleukotriene antagonist, and Ro
      24-4736, a PAF antagonist, in guinea pig and rat models of lung inflammation.

PMID- 7825852
TI  - Modulation of eicosanoid biosynthesis by novel pyridinylpyrimidines.

PMID- 7825853
TI  - Effects of saturated and polyunsaturated fatty acids and their 3-thia fatty acid
      analogues on MCF-7 breast cancer cell growth.

PMID- 7825854
TI  - Suicide inactivation of leukotriene A4 hydrolase/aminopeptidase.

PMID- 7825855
TI  - The x-ray structure and biophysical studies of a 15-lipoxygenase.

PMID- 7825856
TI  - Linoleic acid 8R-dioxygenase and hydroperoxide isomerase of the fungus
      Gaeumannomyces graminis. Mechanism of catalysis and inhibition.

PMID- 7825858
TI  - Inhibition of platelet eicosanoid metabolism by the bacterial phenazine
      derivative pyocyanin.

PMID- 7825857
TI  - Lipoxygenases in human, monkey, and bovine corneal epithelia.

PMID- 7825859
TI  - Effect of quercetin on prostaglandin A1-induced heat shock response in human
      cells.

PMID- 7825860
TI  - Induction of a 32-kDa stress protein by prostaglandin A1 in cultured murine
      cells.

PMID- 7825861
TI  - Metabolism of leukotriene B4 (LTB4) and 12-hydroxy-5,8,10,14-eicosatetraenoic
      acid (12-HETE) in human keratinocytes.

PMID- 7825862
TI  - Interactions of PGH synthase isozymes-1 and -2 with NSAIDs.
AB  - There are two isozymes of prostaglandin endoperoxide (PGH) synthase
      (cyclooxygenase) called PGH synthase-1 and -2 or COX I and II. Both isozymes
      catalyze the same two reactions: oxygenation of arachidonate to yield PGG2 and
      reduction of PGG2 to PGH2. PGH synthase-1 is expressed constitutively and is
      found in most tissues. PGH synthase-2 is undetectable in most cells but can be
      induced in fibroblasts, endothelial cells, ovarian follicles, and macrophages by
      various mitogens, cytokines, and tumor promoters. PGH synthase-1 (PGHS-1) has
      been presumed to be the site of action of nonsteroidal antiinflammatory drugs
      (NSAIDs). However, the discovery of the second isozyme, PGH synthase-2 (PGHS-2),
      and its association with inflammation has suggested that this latter enzyme may
      be the therapeutic target of NSAIDs functioning in their antiinflammatory
      capacities. We have cloned cDNAs for murine PGHS-1 and PGHS-2, expressed these
      enzymes in cos-1 cells, and compared the relative sensitivities of the two
      isozymes to some common NSAIDs. Indomethacin, piroxicam, and sulindac sulfide
      were found to preferentially inhibit PGHS-1. Ibuprofen and meclofenamate inhibit
      both enzymes with comparable potencies. 6-Methoxy-2-naphthylacetic acid, the
      active metabolite of Relafen, inhibits murine PGHS-2 preferentially. Aspirin
      irreversibly inhibits PGHS-1, preventing this isozyme from forming PGH2 or any
      other oxygenated product; in contrast, aspirin treatment of PGHS-2 causes this
      enzyme to form 15-hydroxy-5c,8c,11c,13t-eicosatetraenoic acid (15-HETE) instead
      of PGH2. Our results indicate mouse PGHS-1 and PGHS-2 are pharmacologically
      distinct. Thus, it should be possible to develop agents highly selective for each
      PGHS isozyme. PGHS-2 is not expressed in stomach but is increased by inflammatory
      cytokines in cells such as macrophages. Thus, a selective inhibitor of PGHS-2
      could be an antiinflammatory agent but without being ulcerogenic.

PMID- 7825863
TI  - Prostaglandin H synthase and lipoxygenase gene families in the epithelial cell
      barrier.
AB  - Epithelial barrier cells (in skin, gut, and airway) are both active modulators
      and important targets of the inflammatory response, and some of these cellular
      events may be regulated at a molecular level by products of phospholipid
      arachidonic acid metabolism. Accordingly, we have defined some of the
      characteristics of gene expression and enzyme regulation for distinct members of
      the PGH synthase and lipoxygenase gene families in normal and inflamed epithelial
      tissues and in epithelial cells isolated from mucosal and epidermal tissue (Table
      1). A unifying scheme for our findings includes the following enzymatic systems:
      (i) a PGH synthase-1/PG isomerase pathway responsible for constitutive generation
      of prostaglandins (e.g., PGE2) and maintenance of physiologic epithelial
      function; (ii) a PGH synthase-2/PG isomerase and synthase pathway capable of
      producing additional prostaglandins (e.g., excess PGE2 and/or PGF2 alpha and
      PGD2) especially after stimulation by growth factors and cytokines; and (iii) a
      family of arachidonate 12- and 15-lipoxygenases that may serve to generate
      hydroxy acids (e.g., 12- and 15-HETE) as mediators of basal epithelial function
      and that (after overexpression and oxidant activation) may also catalyze membrane
      peroxidation that contributes to epithelial damage during inflammation. The
      regulatory mechanisms inherent in the control of this scheme provide a
      biochemical rationale for balancing constitutive and inducible oxygenation
      activities and maintaining epithelial barrier function.

PMID- 7825864
TI  - Leukotriene C4 synthase and 5-lipoxygenase activating protein. Regulators of the
      biosynthesis of sulfido-leukotrienes.

PMID- 7825865
TI  - Cytokine regulation of mast cell protease phenotype and arachidonic acid
      metabolism.

PMID- 7825866
TI  - On the positional specificity of 15-lipoxygenase.
AB  - The lipoxygenases comprise a family of fatty acid dioxygenases that are involved
      in a variety of inflammatory conditions. Various approaches have been taken in
      order to understand the different regiospecificities of the different
      lipoxygenases. Here we have reviewed the current knowledge of the structural
      features of the substrate and of the enzyme that form the basis of the
      regiospecificity of 15-lipoxygenase. Earlier experiments on the structural
      features of the substrate were reviewed, as well as more recent results of site
      directed mutagenesis studies. The structure of the soybean lipoxygenase isoform-1
      was also briefly reviewed.

PMID- 7825867
TI  - Brain Corticosteroid Receptors: Studies on the Mechanism, Function, and
      Neurotoxicity of Corticosteroid Action. Proceedings of a conference. Arlington,
      Virginia, March 2-5, 1994.

PMID- 7825868
TI  - Corticosteroid hormones and signal specificity.

PMID- 7825869
TI  - Mechanistic and functional studies of rapid corticosteroid actions.

PMID- 7825870
TI  - Glucocorticoids and stress: permissive and suppressive actions.
AB  - Protection against stress by glucocorticoids is discussed in relation to their
      permissive and suppressive actions. Evidence from the last decade is summarized
      regarding the physiological nature of the suppressive actions, and the hypothesis
      that they prevent stress-activated defense mechanisms from overshooting and
      damaging the organism. Support for this hypothesis has come from observations on
      how endogenous or administered glucocorticoids control inflammatory and immune
      responses, protect in endotoxic and hemorrhagic shock, regulate central nervous
      system responses to stimuli, and moderate many defense reactions through
      suppression of cytokines and other mediators. Studies showing that
      glucocorticoids permissively induce receptors for several mediators that they
      suppress have led to a model in which stimulated activity of a mediator system is
      increased permissively through induction of mediator receptors and decreased
      through suppression of mediator production.

PMID- 7825871
TI  - Corticosteroids and hippocampal plasticity.
AB  - The unexpected discovery in 1968 that the hippocampus takes up and retains
      adrenal steroids has leds to equally unanticipated findings regarding the actions
      of hormones on the brain and the ways in which the brain is capable of changing
      in response to the hormonal milieu. First were indications that adrenal steroids
      adversely affect pyramidal neurons of the hippocampus and cause damage during
      aging and as a result of severe and prolonged stress. Atrophy of dendrites,
      particularly in the CA3 region, appears to be an early index of these effects.
      Second was evidence that the dentate gyrus undergoes atrophy and granule neuron
      death after adrenalectomy; perhaps as a result of this neuronal death,
      neurogenesis is stimulated in dentate gyrus of adult rats. Third are recent
      indications that excitability of hippocampal neurons, including the ability to
      generate long-term potentiation (LTP), is regulated biphasically by adrenal
      steroids. One important goal of current research is to understand the role of
      type I and type II receptors for adrenal steroids in hormonally-induced
      hippocampal plasticity. Type I receptors appear to play a role in containing
      programmed-cell death and the rate of neurogenesis; they also regulate key
      neurochemical features of dentate gyrus and Ammon's horn; and they facilitate
      LTP. Present information indicates that type II receptors inhibit LTP and may
      play a role in the degenerative changes in Ammon's horn.

PMID- 7825872
TI  - Gene products of corticosteroid action in hippocampus.
AB  - We used two methods to examine altered patterns of gene expression in rat
      hippocampus in response to administered glucocorticoids: analysis of RNA in vitro
      translation products on 2-d gels and cloning of cDNAs from a rat hippocampal
      library by differential hybridization (+/- CORT). We determined that two of the
      CORT-responsive cDNA clones encoded the 35- and 50-kd RNA translation products
      and identified them as GPDH and GFAP, respectively, by sequence analysis. Cloned
      mRNAs that increased and decreased in response to CORT were determined to be
      under positive and negative regulation by glucocorticoids in intact rats. Despite
      their similarities in glucocorticoid response characteristics, we found three
      subsets of hippocampal mRNA responses to CORT and shaking stress which differ in
      temporal and level-dependent aspects of CORT regulation. In addition, GPDH gene
      expression represents a glucocorticoid-dependent stress response which is rapidly
      increased in a dose- and stressor-dependent manner. It is a candidate for a
      sensitive indicator of stress responsiveness in the brain as a function of
      neuroendocrine activity. Mechanisms of adaptation to stress in the brain are
      likely to involve responses that are both mediated by glucocorticoids and opposed
      by them. GFAP and TGF-beta 1 mRNA responses may be examples of the latter, since
      they are decreased in response to glucocorticoids, are under negative regulation
      by glucocorticoids in intact rats, and are increased in response to brain injury
      and disease and during aging. If these astrocytic and microglial responses are
      involved in cellular defense mechanisms in the brain, then their regulation by
      glucocorticoids would be important in maintaining and restoring cellular
      homeostasis in physiological and pathophysiological states. Future studies using
      these sensitive probes for glucocorticoid-regulated gene expression may identify
      new mechanisms by which the brain coordinates acute and chronic responses to
      stress and disease.

PMID- 7825873
TI  - Corticosteroid-induced proteins in brain.
AB  - Cumulative exposure of hippocampal neurons to stress-like levels of
      corticosterone produces a negative spectrum of cellular alterations from
      ultrastructural changes to disruption of dendritic morphology and eventual
      degeneration. An experimental system which adapts itself to characterization of
      corticosteroid-induced proteins which mediate such effects is the hippocampal
      slice incubated in the presence of a radiolabeled amino acid following treatment
      of rats with corticosterone. The most consistently observed response to elevated
      corticosterone levels produced by exogenous injection is synthesis of a
      hippocampal cytosolic protein which has characteristics of glycerol phosphate
      dehydrogenase. Because synthesis of this protein is enhanced with a short latency
      as serum corticosterone levels are increased and terminated quickly upon re
      establishment of basal conditions, it serves as a valid biological marker of the
      response of the hippocampus to short-term stress. In contrast, alterations in
      synthesis of other proteins following corticosterone treatment only become
      apparent under defined conditions or after chronic treatment. For example,
      steroid-inhibited synthesis of a hippocampal protein with an approximate
      molecular weight of 25,000 is only observed when slices are incubated at an
      elevated temperature. Such negative changes may represent loss of adaptive
      responses that protect the neuron from damage by cellular insults.

PMID- 7825874
TI  - Gene-mediated control of hippocampal neuronal excitability.

PMID- 7825875
TI  - Dexamethasone reverses adrenalectomy-induced neuronal de-differentiation in
      midbrain raphe-hippocampus axis.
AB  - Differentiation leads to specific morphological and biochemical characteristics.
      We examined whether epigenetic factors (e.g., glucocorticoids) are required to
      maintain neuronal differentiation in the adult brain. In the midbrain,
      adrenalectomy (ADX) (1-2 wk) reduced the size of tryptophan hydroxylase (WH)
      immunoreactive (IR) neurons. ADX rats exposed to short-term (24-72-h)
      dexamethasone (ST-DEX) in the drinking saline (10 mg/l) showed an increase in WH
      protein, somal area and dendritic size of WH-IR neurons. In the hippocampus, ADX
      for 2-3 mo (long-term; LT) reduced Nissl staining, calbindin (CBD)-IR and 5-HT1A
      receptor mRNA in the granular cell layer, and the size of the molecular layer and
      its CBD-IR dendrites. Small vimentin (Vim)-IR glial cells emerged in the granular
      layer. ST-DEX after LT-ADX rapidly induced a recovery of 5-HT1A mRNA, Nissl
      labeling and CBD-IR in the granule cell layer. In the molecular layer, there was
      an increase in the area and in the number of CBD-IR dendrites. Furthermore, the
      Vim-IR glial cells were enlarged in size and branching. The rate of cell
      proliferation was studied in these animals. Immunostaining with antibodies
      against proliferating cell nuclear antigen (PCNA) and use of bromouridine argue
      against enhanced neurogenesis after ST-DEX in LT-ADX. We propose that
      glucocorticoids induce and maintain differentiation of serotonergic and CBD-IR
      neurons in the midbrain-hippocampal axis. A neuronotrophic role for the glial 5
      HT1A receptor is suggested.

PMID- 7825876
TI  - Glucocorticoids and neurotrophin gene regulation in the nervous system.

PMID- 7825877
TI  - Steroid regulation of cytokines. Relevance for TH1-to-TH2 shift?

PMID- 7825878
TI  - Downregulation of the glucocorticoid receptor. A mechanism for physiological
      adaptation to hormones.

PMID- 7825879
TI  - Corticosteroids and the control of function in the hypothalamo-pituitary-adrenal
      (HPA) axis.

PMID- 7825880
TI  - Pharmacology of neurosteroid biosynthesis. Role of the mitochondrial DBI receptor
      (MDR) complex.

PMID- 7825881
TI  - In vitro studies of glucocorticoid effects on neurons and astrocytes.
AB  - Studies using immunocytochemistry and RNase protection assay demonstrate that
      glucocorticoid and mineralocorticoid receptors (GR, MR) and their corresponding
      mRNAs are co-expressed in hippocampal neurons cultured in serum-free, defined
      medium and at lower levels in cultured astrocytes. Addition of serum or medium
      conditioned by astrocytes increases the levels of MR mRNA, but has little effect
      on the levels of GR mRNA. Cellular levels of both GR mRNA and MR mRNA are
      upregulated by growth of embryonic hippocampal neurons in corticosterone. This is
      in distinct contrast to regulation of receptor expression in vivo where mRNAs for
      these receptors are downregulated in the rat hippocampus by corticosterone
      treatment of the adult adrenalectomized rat. However, in cultured astrocytes, GR
      and MR mRNAs are also downregulated by corticosterone. To begin to define the
      role of glucocorticoids in gene expression in astrocytes, we have used giant two
      dimensional (2D) gel electrophoresis to separate astrocyte cellular proteins and
      translation products synthesized in vitro from astrocyte poly A+ RNA. Analysis of
      approximately 1,500 in vitro translation products by giant 2D gel electrophoresis
      reveals 11 protein inductions and 1 repression that occur at the level of mRNA in
      the absence of protein synthesis following treatment of astrocytes with
      corticosterone. Interestingly, these changes appear to be mediated by GR, but not
      by MR. The in vitro studies described here are relevant to identifying the role
      of GR and MR in gene expression in specific cell types in the hippocampus.

PMID- 7825882
TI  - Environmental regulation of the development of glucocorticoid receptor systems in
      the rat forebrain. The role of serotonin.

PMID- 7825884
TI  - The physiological relevance of glucocorticoid endangerment of the hippocampus.

PMID- 7825883
TI  - The ontogeny of the hypothalamic-pituitary-adrenal axis. The influence of
      maternal factors.

PMID- 7825885
TI  - The glucocorticoid hypothesis of age-related hippocampal neurodegeneration: role
      of dysregulated intraneuronal calcium.

PMID- 7825886
TI  - Hypothalamic-pituitary-adrenal axis regulation and human aging.

PMID- 7825887
TI  - Corticosteroid action and neuroendocrine-immune interactions.
AB  - Glucocorticoid feedback during inflammation depends on several factors, including
      effective corticosteroid concentrations, the temporal coordination between the
      immune system and the HPAA, and sensitivity of the target organ to
      corticosteroids. In the case of LEW/N rats, several lines of evidence indicate
      that CRH is aberrantly regulated, and as a consequence, the circulating
      corticosterone concentrations are blunted. In addition, basal ACTH and
      corticosterone responses differ compared to SD and F344/N rats. Therefore
      glucocorticoid feedback during inflammation is impaired leading to uncontrolled
      inflammation as observed in various models. We found that in the LEW/N rat, the
      regulation of the GR and MR, at least in the hippocampus, is different from
      F344/N rats. A similar impaired upregulation of the GR has been described in aged
      rats, and this has been postulated to be the cause of the altered HPAA reactivity
      after various stimuli in these rats. Moreover, adult LEW/N rats exhibit HPAA
      responses which resemble those observed during the stress hyporesponsive period
      of immature SD or F244/N rats. These latter data suggest that in the LEW/N rat
      the ontogeny and/or regulation of the HPAA is disturbed. Taken together, the
      impaired regulation of HPAA reactivity observed in LEW/N rats could be due to an
      impaired regulation of the central MR and/or GR. Although no data of GR dynamics
      in the context of local inflammation are available yet, this could be an
      additional factor determining tissue sensitivity and immune responses to
      corticosteroids. In humans, determination of the role of the HPAA in inflammation
      is more complex due to the much higher intrinsic variability between
      subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7825888
TI  - Regulation of the hypothalamic-pituitary-adrenal axis in dementia disorders.
AB  - In 163 patients with dementia disorders, subdivided into Alzheimer's disease with
      early onset (AD; n = 40), senile dementia of the Alzheimer type (SDAT; n = 56),
      vascular dementia (VAD; n = 45) and dementia of unspecified type (NUD; n = 22)
      the dexamethasone suppression test (DST) was performed. The patients were rated
      according to the DSM-III-R criteria as having mild, moderate or severe dementia
      and were also assessed using the GBS scale which gives a profile of the dementia
      syndrome. In the total group of dementia there were significant correlations
      between severity of dementia and post-DST levels. The frequency of pathological
      DST also correlated significantly with the severity of dementia. In the subgroups
      of dementia a strong correlation between severity of dementia and high post-DST
      cortisol levels was found only in the VAD group. Between the subgroups of
      dementia disorders there were no significant differences in basal cortisol
      levels. The percentage of pathological DST was lowest in the AD group (40%). It
      was somewhat higher in the VAD group (49%), still higher in the SDAT group (54%)
      and highest in the NUD group (59%). When the relationship between post-DST
      cortisol levels and GBS scores was analyzed, significant correlations were found
      mainly in the VAD group. There intellectual impairment, anxiety, fear-panic and
      restlessness correlated significantly with post-DST cortisol levels. The results
      indicate hypothalamic overactivity in a substantial number of demented patients.
      In VAD and to a certain extent also in SDAT a disconnection between cortical
      areas, including the hippocampus, and the hypothalamus is assumed. Overactivity
      in the hypothalamic-pituitary-adrenal (HPA) axis is due to stress, and an
      insufficient feedback system leads to chronic stress adaptation failure.

PMID- 7825889
TI  - Steroid effects on central neurons and implications for psychiatric and
      neurological disorders.
AB  - Acute and chronic stress as well as a number of psychiatric and neurological
      disorders are accompanied by profound disturbances of the HPA system. These
      neuroendocrine alterations act back on the central nervous tissue mainly via
      corticosteroids-affecting glucocorticoid and mineralocorticoid receptors. The
      major conclusions drawn from studies probing these receptors in clinical
      investigations are: (1) In many such conditions central corticosteroid receptors
      are weakened in their capacity to curtail spontaneous and stress-elevated
      corticosteroid levels; (2) the combined DEX-CRH test is the best neuroendocrine
      tool currently available for identifying HPA abnormalities in psychiatric
      patients; (3) in depression the decreased corticosteroid receptor capacity in
      transient, and antidepressants act through reinstatement of GR and MR function
      probably resulting in reduced hypothalamic CRH and AVP production; (4) several
      neurological disorders such as MS and HIV infection are often accompanied by
      altered HPA function, which has therapeutic implications; and (5) various
      corticosteroids, their biosynthetic precursors and their metabolites have
      differentiable effects on the sleep EEG, which can be attributed to their mode of
      action; specifically, steroids such as pregnenolone and DHEA most likely are
      produced in glia cells and act in a paracrine fashion at neurons, thus modifying
      the sleep EEG in humans in a manner that suggests their potential as memory
      enhancers.

PMID- 7825890
TI  - Glucocorticosteroid resistance in humans. Elucidation of the molecular mechanisms
      and implications for pathophysiology.
AB  - Familial glucocorticoid resistance (FGR) is a rare hereditary disorder
      characterized by hypercortisolism and the absence of stigmata of Cushing's
      syndrome. The inability of glucocorticoids to exert their effects on target
      tissues is compensated for by increases in circulating corticotropin (ACTH) and
      cortisol, the former causing excess secretion of both adrenal androgens and
      adrenal steroid-biosynthesis intermediates with salt-retaining activity. There is
      considerable variability in the clinical presentations of FGR ranging from
      asymptomatic, to isolated chronic fatigue and to hypertension with or without
      hypokalemic alkalosis or to hyperandrogenism, or both. In women, hyperandrogenism
      can result in acne, hirsutism, menstrual irregularities, oligoanovulation, and
      infertility; in men it may lead to infertility and in children to precocious
      puberty. The reported molecular defects in FGR, such as point mutations and a
      microdeletion of the glucocorticoid receptor (GR) gene, cause partial resistance
      by, respectively, compromising the function of the GR or decreasing its
      intracellular concentration in glucocorticoid target tissues. Complete
      glucocorticoid resistance is believed to be incompatible with life in humans.
      Hence, the glucocorticoid resistance cases reported have been partial and of
      variable degree. The extreme variability in the clinical manifestations of the
      disorder can, additionally, be explained by differing sensitivity of target
      tissues to mineralocorticoids or androgens or both, and perhaps by different
      biochemical defects of the glucocorticoid receptor, causing selective resistance
      of certain glucocorticoid responses in specific tissues. Isolated tissue
      resistance from a somatic mutation of the GR in a corticotropinoma from a patient
      with Nelson's syndrome was also found, suggesting that this may be a mechanism of
      tumorigenesis. There is additional evidence that defects of GR function can
      appear surreptitiously in a variety of clinical conditions, suggesting that
      glucocorticoid resistance in humans may be involved in the pathogenesis and/or
      clinical picture of a plethora of disease states, of which FGR is the archetype.

PMID- 7825891
TI  - Circadian regulation of basal cortisol levels in posttraumatic stress disorder.

PMID- 7825892
TI  - Altered responses of cortisol, GH, TSH and testosterone to acute stress after
      four months' practice of transcendental meditation (TM).

PMID- 7825894
TI  - Behavioral and endocrine impact of impaired type II glucocorticoid receptor
      function in a transgenic mouse model.

PMID- 7825893
TI  - Effects of hydrocortisone infusion on rCBF in schizophrenic patients during a
      memory task. An O15 PET Study.

PMID- 7825895
TI  - Corticosterone potentiation of conditioned fear in rats.

PMID- 7825896
TI  - Modulation of the locomotor response to amphetamine by corticosterone.

PMID- 7825897
TI  - Evidence for nitric oxide-mediated rapid locomotor effects of corticosterone in a
      novel environment.

PMID- 7825898
TI  - Glucocorticoid receptor (GR)-mediated effects on cocaine kindling in rats.

PMID- 7825899
TI  - Stress-dependent impairments of spatial memory. Role of 5-HT.

PMID- 7825900
TI  - Adrenalectomy impairs spatial memory in rats.

PMID- 7825901
TI  - Adrenalectomy leads to a different responsiveness to 8-OH-DPAT in a water-maze
      learning task.

PMID- 7825902
TI  - Stress impairs LTP and hippocampal-dependent memory.

PMID- 7825903
TI  - Hypertension and the mineralocorticoid receptor in the brain.

PMID- 7825904
TI  - The effects of RU 38486 and RU 28318 on energy balance of ovariectomized rats.

PMID- 7825906
TI  - Social defeat impairs plasma corticosterone response to the 5-HT1A agonist 8-OH
      DPAT in the rat.

PMID- 7825905
TI  - Glial and neuronal glucocorticoid receptor immunoreactive cell populations in
      developing, adult, and aging brain.
AB  - A detailed mapping of glucocorticoid receptor (GR) immunoreactivity (IR) in rat
      CNS was performed employing a mouse monoclonal antibody against rat liver GR.
      Subjective comparisons were made between the present results and the available
      data in the literature. A semiquantitation of GR immunostaining was found
      necessary and was obtained by microdensitometric and morphometric techniques,
      which enabled the distinction of neuronal and glial cell populations containing
      GR IR in various CNS regions. GR IR in the CNS was mainly found in the nuclear
      compartment. The GR was present in neuronal populations with classical
      neurotransmitters, especially monoamines and glutamate and with various
      neuropeptides. The degree of colocalization varied according to the function of
      the brain area. Functional implications were made in relation to stress
      sensitivity, mood and nociception/antinociception. The global control of networks
      by glucocorticoids may allow an optimal integration of different types of
      circuits. The GR is found already in the fetal rat and the development of GR mRNA
      and receptor protein was followed during the pre- and postnatal periods. The GR
      appears to be a major factor in brain maturation and in modulation of stress
      responses. In aged Brown Norway rat brain GR IR but not mineralocorticoid
      receptor (MR) IR is reduced in the hippocampal nerve cells. The intensity of GR
      IR but not the number of nerve cells is altered, indicating a reduced activation
      of the GR in aging in this rat strain. Overall GR participates in neuronal
      plasticity from fetal and postnatal life to adult life and aging.

PMID- 7825907
TI  - Regulation of hippocampal glucocorticoid receptor gene expression by psychosocial
      conflict.

PMID- 7825908
TI  - Sex differences in type I corticosteroid receptor binding in selective brain
      areas of rats.

PMID- 7825909
TI  - Interaction of progesterone with the hippocampal mineralocorticoid receptor.

PMID- 7825910
TI  - Lesion of the central nucleus of the amygdala decreases basal CRH mRNA expression
      and stress-induced ACTH release.

PMID- 7825912
TI  - Effects of chronic antidepressant treatment on the hypothalamic-pituitary-adrenal
      axis of Wistar rats.

PMID- 7825911
TI  - The role of lipocortin 1 (LC1) in the steroid feedback control of hypothalamo
      pituitary-adrenocortical function. In vivo studies.

PMID- 7825913
TI  - Early glucocorticoid inhibition of hormone release in pituitary corticotrope
      cells is voltage dependent.

PMID- 7825914
TI  - Modulation of carbachol responsiveness by corticosteroid hormones in rat CA1
      pyramidal neurons.

PMID- 7825916
TI  - Central and systemic corticosterone differentially affect dopamine and
      norepinephrine in the frontal cortex of the awake freely moving rat.

PMID- 7825915
TI  - Calbindin-D28K and parvalbumin immunoreactivity in the rat hippocampus following
      adrenalectomy and corticosterone treatment.

PMID- 7825917
TI  - Dexamethasone does not prevent apoptosis in the hippocampus of the rat.

PMID- 7825918
TI  - Glucocorticoid receptor-mediated repression of GnRH gene expression in a
      hypothalamic GnRH-secreting neuronal cell line.

PMID- 7825919
TI  - Effect of dexamethasone and forskolin on neurotensin expression in hypothalamic
      cells in culture.

PMID- 7825920
TI  - Glucocorticoid stimulation of sodium channel expression in cultured astrocytes.

PMID- 7825921
TI  - Glucocorticoid regulation of stress-induced mineralocorticoid receptor gene
      transcription in vivo.

PMID- 7825922
TI  - The functional relevance of the heteromeric structure of corticosteroid
      receptors.

PMID- 7825923
TI  - The binary corticosteroid response: transcriptional regulation by mineralo- and
      glucocorticoid receptors.

PMID- 7825924
TI  - Brain mineralocorticoid receptor function.

PMID- 7825926
TI  - 'Health at work'--getting the balance right.

PMID- 7825925
TI  - Corticosteroid receptor modulation in transgenic mice.

PMID- 7825927
TI  - Health promotion at work--a new paradigm for workplace health.

PMID- 7825928
TI  - Improving the health of people at work.

PMID- 7825929
TI  - Approaches for estimating the distribution of short-term exposure concentrations
      for different averaging times.
AB  - Because the distribution of short-term exposure concentrations is approximately
      log-normal within 1 day, the geometric mean (GM) and geometric standard deviation
      (GSD) are critical parameters for obtaining the overall view of exposure, but
      when the averaging time changes, so too do the GM and GSD, though the arithmetic
      mean (AM) should be fixed. For industrial hygienists the ability to transform the
      GM and GSD from one averaging time to another is very useful. Three approaches
      for estimating the GM and GSD for different averaging times were applied to 10
      workers (16 worker-chemical combinations). The random approach is based on the
      assumption that exposure concentrations vary randomly over time. On the other
      hand, two autocorrelation approaches are based on an assumption that the exposure
      time series are autocorrelated. This study showed that the random approach tended
      to lead to positive-biased and negative-biased estimates for the GM and GSD,
      respectively. The two types of the autocorrelation approach generally gave
      unbiased estimates, but the dispersions of the estimates became large when the
      ratio of the new averaging time to the original one was large.

PMID- 7825930
TI  - Does the wearing of sampling pumps affect exposure?
AB  - There is a possibility that wearing traditional sampling pumps could affect
      worker behaviour and undermine the validity of occupational hygiene exposure
      measurement. Sampling pumps are bulky and can be noisy, and if these
      characteristics alter work patterns sufficiently exposures may be modified. This
      paper describes a carefully controlled pilot study designed to test the
      hypothesis that the wearing of personal sampling pumps may affect workers'
      exposure. Comparisons were made using pump-based systems and diffusive samplers
      to measure organic vapours. Diffusive samplers were chosen as controls because
      they are much less bulky and therefore less likely to affect behaviour. A
      carefully constructed sampling strategy, involving measurements on between 13 and
      20 workers on 6 working days, was used at five sites. On alternate days both
      sampling methods were used, side-by-side, on the workers and on the remaining
      days only diffusive samplers were worn. The sites chosen had minimal day-to-day
      variation in environmental conditions. The results showed that at one site the
      concentrations were approximately 50% higher on the days when pumps were worn
      compared with other days. At the remaining sites no significant differences were
      found. From the characteristics of the work at the site where differences were
      observed it is suggested that pumps may affect measured concentrations when
      people have flexible work patterns and spend part of their time seated and/or the
      work is in quiet areas.

PMID- 7825931
TI  - A novel lighting system for the measurement of dermal exposure using a
      fluorescent dye and an image processor.
AB  - A video technique is described which uses a fluorescent dye as a tracer to
      quantify dermal deposition of chemicals such as pesticides. The subject stands
      inside a dodecahedral arrangement of ultraviolet (u.v.) strip-lights, which cause
      a given area of dye to fluoresce with a consistent intensity over a range of
      spatial and angular positions within the lighting field. A special algorithm and
      an additional point source light enable local compensation factors to be
      calculated to allow for the reduction of apparent surface areas, due either to
      the foreshortening of surfaces angled to the camera or to the inverse square law
      for surfaces further from the camera. Measurements on planar surfaces prove that
      the algorithm performs well in a large central region inside the dodecahedral
      lighting field. Field trials of the system show that although the free-standing
      apparatus is large and rather unwieldy, when fastened inside a box van it is
      practicable, portable and self-contained. It is suitable for measuring exposure
      arising from spraying operations and can be used, but with more limited success,
      in studies of dipping operations.

PMID- 7825932
TI  - Death following exposure to fine particulate nickel from a metal arc process.
AB  - A man was taken ill suddenly while spraying nickel using a thermal arc process.
      He was relieved of his duties and sent home. His condition deteriorated and he
      was admitted to hospital with a diagnosis of pneumonia. Thirteen days after
      exposure he died. At post mortem examination the cause of death was determined to
      be shock lung or Adult Respiratory Distress Syndrome (ARDS). Reproduction of the
      conditions under which the man had operated the metal arc process produced nickel
      concentrations of 382.1 mg m-3 in the air next to the operator. Of this nickel,
      64.6% was in the form of particles less than 1.4 microns in diameter; the
      majority being 50 nm in diameter. The total amount of nickel inhaled by the man,
      who operated the process for 90 min, was estimated to be nearly 1 g. The toxicity
      of the nickel is thought to be associated with the very fine particulate nature
      of the metal fume and the large amount inhaled. The importance of wearing
      adequate protective equipment while operating this metal arc process is stressed.

PMID- 7825933
TI  - Quality of the occupational hygiene profession in Europe.

PMID- 7825934
TI  - Dustiness testing and moving towards a biologically relevant dustiness index.
AB  - This communication reviews the progress so far in dustiness measurements and
      summarizes recent research into an improved dustiness tester. A dustiness index
      based on the three biologically relevant aerosol fractions is proposed. Finally
      the paper looks ahead at the future direction of the work.

PMID- 7825935
TI  - Fatal intoxication due to an unexpected presence of carbon dioxide.
AB  - A fatal accident which occurred in a tank containing a sludge made of wine and
      activated charcoal is described. Similar accidents in the wine industry seem to
      have never been reported before. Initially, the cause of death was not obvious
      and became clear only after the autopsy confirmed the presence of a very high
      concentration of carbon dioxide in blood. It is shown in this paper how the
      concentration of carbon dioxide in the tank could be estimated from its
      solubility in water, assuming a realistic content of this gas in the wine
      remaining in the sludge. Moreover the accident was analysed by the fault tree
      method which revealed that, as well as the deficiencies in risk management of
      such companies, the unsuspected presence of carbon dioxide played a significant
      role.

PMID- 7825936
TI  - [Fixed retraction pockets and cholesteatoma in children. Authors' experience with
      199 cases].
AB  - Cholesteatoma is more destructive in the child than in the adult, but few studies
      have examined the outcome as a function of age. The authors evaluated
      retrospectively their experience in 199 cases of cholesteatomas or uncontrollable
      fixed retraction pouches in children under the age of 15. Mean follow-up was 2
      and a half years and the anatomic and functional results are detailed. Reasons
      for performing first intention or second intention canal wall up or down
      procedures were analyzed as a function of age. Residual cholesteatomas were
      particularly frequent in whatever the initial surgical procedure. Cholesteatomas
      and retraction pouches in the child under 5 (n = 24) were particularly aggressive
      and destructive, often requiring a canal wall down operation. Residual
      cholesteatomas were also very frequent and involved both bony and functional
      element of the petrus. The clinical course of cholesteatoma in the young child
      appears to be very different, becoming less destructive as the child reaches
      adulthood.

PMID- 7825937
TI  - [Cutaneous neuroendocrine carcinoma of the external ear canal].
AB  - Authors report a case of a neuroendocrine carcinoma (Merkel cell tumor) located
      in the external meatus. These tumors have a fearsome prognostic.
      Immunohistochemical study has become indispensable to make the diagnosis. A
      literature review is presented, and therapeutic choices discussed. Wide and
      precocious surgical resection is advised.

PMID- 7825938
TI  - [Injectable collagen, 10 years after...].

PMID- 7825939
TI  - [Contribution of x-ray computed tomography in the diagnosis of cervical
      suppuration].
AB  - The authors report their experience with computed tomography (CT) in 27 cases of
      cervical suppurations. The diagnosis was confirmed surgically in 24 cases and by
      the improvement of clinical signs and CT after antibiotics in 3. Two types of CT
      features were identified: collected abscesses (n = 22) visualized as encapsulated
      heterogeneous hypodense formations and extensive suppurative cellulitis (n = 5)
      formed by large diffuse hypodense collections without a clearly visible
      peripheral wall. The extension of the suppurative process could be evaluated
      precisely with CT, especially in certain anatomic areas where physical
      examination is difficult including mediastinal suppurations (n = 2), extension of
      parapharyngeal suppurations to the retrostyleal area (n = 1), and pterygo
      maxillary and epidural collections (1 each) the latter in combination with a
      tuberculous abscess. Computed tomography is also useful in the etiological
      diagnosis (search for foreign body, cystic malformations, tuberculosis) and in
      post-treatment follow-up to visualize the absence of collections after cure in
      cases of favourable outcome and to determine the extent of the suppurative
      process in case of complications.

PMID- 7825940
TI  - [Minor malformations of the ear ossicles. New classification and therapeutic
      results].
AB  - We tried to classify 46 minor malformations in 5 groups: 0: Normal ossicular
      chain, almost normal tympanic membrane but small atretic plate around malleus
      handle. I: Fixation of the malleus head. II: Normal ossicular chain but fixation
      of the footplate with or without abnormality of the facial nerve. III: Lack of a
      part of the ossicular chain with or without abnormality of the stapes. IV: Severe
      malformation of all the ossicular chain. We operated upon 4 malformations of type
      0, 8 of type I, 10 of type II, 14 of type III and 10 of type IV. An air-bone gap
      within 20 dB was achieved in only 15 cases. As a matter of fact, in 9 cases the
      facial nerve covered the oval window; there were 4 pseudo-Mondini; ossiculoplasty
      was performed on a totally modified footplate in one case.

PMID- 7825941
TI  - [Test of electrical stimulation of the round window. Diagnostic and prognostic
      value of the rehabilitation of total deafness by cochlear implant].
AB  - The round window electrical stimulation (RWES) test has been performed in 708
      cases of total deafness. Among them 244 have successfully benefited with a
      cochlear implant. Electrical Brain Stem Evoked (EBSE) potential elicited by this
      stimulation have been registrated in 283 cases, 113 of them during general
      anesthesia necessary in children. This test supplies the patient with a
      subjective sound sensation and/or EBSE in 93% of cases. The correlation between
      electrical data of this RWES test and clinical results of the cochlear implant is
      described. This test is discussed regarding the simple transtympanique
      promonotory stimulation test.

PMID- 7825942
TI  - [Value of magnetic resonance imaging associated with x-ray computed tomography in
      the screening of residual cholesteatoma after primary surgery].
AB  - Several recent studies have described the magnetic resonance imagery (MRI) of
      cholesteatomas. For certain authors the MR images are specific after Gadolinium
      injection. This radio-surgical study included 16 patients who underwent a
      tympanoplasty with supra and retromeatic masto-attictomy for a cholesteatoma and
      for whom a second operation was planned. Computed tomography (CT) and MRI was
      performed before operation in all patients with and without injection of
      Gadolinium. Images were then correlated with peroperative observations. Based on
      the CT and MRI diagnostic criteria of cholesteatoma reported in the literature,
      the radio-surgical correlation was false in 8 out of 16 cases (false negatives,
      false positives, partial errors). Among the 8 true correlations, 5 were normal
      images confirmed by the absence of cholesteatomy on operation. MRI with and
      without Gadolinium cannot be used to screen for small residual cholesteatomas or
      to determine the characteristics of an opacity of the middle ear seen on computed
      tomography.

PMID- 7825943
TI  - [Value of the monitoring of the facial nerve in the evaluation of facial function
      in translabyrinthine surgery for acoustic neuroma].
AB  - Amongst the 62 patients operated for acoustic neuroma using a translabyrinthine
      approach, the authors study post operatory results at one month of the facial
      function according to the "House-Brackmann" classification. The analysis consists
      in 2 homogeneous and comparable series of 34 and 28 patients having benefited or
      not of a per operatory monitoring of the facial nerve with "NIM 2" neuro monitor.
      Without distinction of the tumoral sizes 76% of patients show a good facial
      result when monitorized against 60.7% when not. According to the tumoral size
      monitoring becomes more interesting: also you will find better results in the
      monitorized serial (71%) against 29% without. Other factors concerning the facial
      post operatory functions are also analysed by authors. To the very important part
      of per operatory monitoring, the anatomical status, microvascularization and
      physiological state of the nerve al as well as the operator's experience are to
      be added. All above factors must be considered when evaluating the final post
      operatory facial result.

PMID- 7825944
TI  - [Audiophonologic aspects of the decision and follow-up of cochlear implants in
      children].
AB  - Based on the audiologic, audioprosthetic, psychological and orthophonic criteria
      involved in the decision for a cochlear implant in 16 children (age 5 to 18), a
      protocol including 10 criteria was developed for children with severe deafness
      and a low to very low level of oral language acquisition. The importance of the
      motivation of the family, their capacity to become implicated and their desire to
      listen to the child and communicate orally with him, as well as the role of the
      specialist teachers were emphasized. In this series of 16 children the results of
      the implantation work-up lead to only 9 cases of implantation.

PMID- 7825945
TI  - [Thromboembolic disease in patients aged 80 and over. Diagnostic and therapeutic
      strategies].
AB  - The aim of this retrospective study of 50 deep vein thromboses (DVT) of the lower
      limbs in patients aged 80 and over (35 women, including 2 with bilateral DVT and
      13 men), mean age 83.37 +/- 2.72, hospitalised in a department of cardiology, was
      to assess the diagnostic value of ultrasound investigations, clinical parameters
      and results of treatment of thrombo-embolic disease in this age group. High DVT
      were found in 76 per cent of cases and pulmonary embolism occurred in 52.1 per
      cent of cases, its incidence increasing with age. One third of DVT were
      asymptomatic and presented as pulmonary embolism, the predominant clinical
      feature being edema in the absence of other signs. The existence of atrial
      fibrillation was associated in 90 per cent of cases with a pulmonary embolism.
      Venous Echo-Doppler is also the key investigation in the diagnosis of thrombo
      embolic disease. Cardiac Echo-Doppler seems particularly useful in the diagnosis
      of pulmonary embolism when more than 40 per cent of the vascular bed is cut off.
      Thrombolytic treatment remains possible after the age of 80 in life-threatening
      situations. Overall hospital mortality remains high (10.4 per cent) and appears
      to be due chiefly to the onset of a pulmonary embolism which is not thrombolyzed
      since considered insufficiently serious or occurring in a situation in which
      fibrinolysis is theoretically contra-indicated.

PMID- 7825946
TI  - [Infarction in patients aged over 70. Apropos of 194 patients].
AB  - Among 498 patients hospitalised for myocardial infarction during a three year
      period, 194 (39%) were aged over 70 (mean age: 78.6 +/- 6), including 99 women
      and 95 men. Comparison of this group of patients with those aged under 70 showed
      a significantly higher hospital mortality (17.5% v. 6.5%) (p < 0.01) and a higher
      acute complication rate (60.8% v. 23.7% (p < 0.01), in particular after the age
      of 75. Twenty-eight patients were treated by thrombolysis (14.4% v. 50.6%) (p <
      0.05), with a 79.2% patency rate in follow-up angiography at 48 h, and only one
      non-fatal hemorrhagic complication. Eighty-six patients were investigated by
      coronary arteriography (44.9% v. 87.2% (p < 0.05) without any complication. Mean
      ejection fraction was 57.3 +/- 13.5%. Fifty patients were treated by angioplasty
      (24.6% v. 57%) (p < 0.01) including 15 during the acute phase, with primary
      success in 40 of them (80%). Ten patients underwent coronary bypass following
      their infarction (5.1% v. 6.25%) (NS) with two per- or postoperative deaths
      (20%). Follow-up study revealed high secondary mortality with an overall survival
      rate at one year of 59.6% v. 81% in patients aged under 70 (p < 0.01). In total,
      infarction in the elderly is characterised by high mortality and morbidity as
      compared with infarctions in patients aged under 70, and requires active
      management during the acute phase, assessed according to the physiological status
      and age of the patient.

PMID- 7825947
TI  - [Complete vagal block in the clinical evaluation of sinus bradycardia].
AB  - The authors determined the discriminant threshold of sinus rate (SR) and the
      degree of its increase after complete vagal block (0.04 mg/kg of atropine sulfate
      IV) in 34 patients with symptomatic sinus bradycardia, the day after
      electrophysiological evaluation (performed before and after autonomic block with
      propranolol 0.2 mg/kg and atropine sulfate 0.04 mg/kg IV). Patients were divided
      into two groups. Group I included 19 patients (age 43.3 +/- 8) with normal
      intrinsic sinus automatism with normal intrinsic heart rate (IHRo) and normal
      intrinsic corrected sinus recovery time (intrinsic CSRT) (< 425 ms). Group II
      consisted of 15 patients (age 51.8 +/- 12) with abnormal intrinsic sinus
      automatism with abnormal IHRo and/or intrinsic CSRT (> 425 ms). Following the
      atropine test, SR in the individuals of Group I increased from 58.1 +/- 11.7 bpm
      to 103 +/- 16 bpm (delta% = 80 +/- 37), while in Group II it increased from 52.8
      +/- 12 bpm to 82.15 bpm (delta% = 55.4 +/- 21). The discriminant threshold of SR
      and of its percentage increase (delta%) were 91 bpm and 68% respectively, with a
      sensitivity of 71 and 81% and a specificity of 73 and 63%. The predictive value
      of a positive test of SR (< 91 bpm) and of its delta% (< 68%) were 71 and 64%
      respectively. That of a negative test of SR (> 91 bpm) and of its delta% (< 68%)
      were 73 and 80% respectively. The total predictive accuracy of SR and of its
      percentage increase was the same: 72%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7825948
TI  - [New lipid factors of cardiovascular risk].
AB  - Each hyperlipidemia patient requires individual management. Treatment choices are
      thus made for each patient on the basis of evaluation of their overall
      cardiovascular risk. This evaluation involves four types of characteristics:
      those which cannot be changed (age, gender), classical lipid and non-lipid risk
      factors, and finally cardiovascular status with two types of evaluation (clinical
      status and sub-clinical, atherosclerosis). Three examples are presented here,
      enabling more precise assessment of lipid risk: syndrome X which shows to what
      extent risk factors are often associated, combined familial hyperlipidemia which
      emphasises the importance of family history, and lipoprotein (a). The latter is a
      risk factor relatively inaccessible to treatment but which enables better
      evaluation of the risk of the patient and choice of a stricter treatment goal
      when it is very high.

PMID- 7825949
TI  - [Treatment of moderate hypertension: monotherapy or combination?].
AB  - The treatment of hypertension must fall within a strategy of the early and strict
      control of blood pressure levels. Only actual normalisation of blood pressure can
      offer long term benefit regarding the incidence of cardiovascular morbidity and
      mortality. While major studies undertaken up to now have already proven the
      benefit of treatment using classical drugs as monotherapy, it is now necessary to
      offer all young hypertension patients, even mild, with strict control of levels,
      a non-pharmacological action on risk factors, and a choice of treatments ensuring
      no loss of part of the prognostic benefit as a result of persistence or worsening
      or sub-clinical metabolic disorders. It seems logical, when first-line
      monotherapy is selected from among the five major drug groups recommended, is
      neither perfectly effective nor perfectly tolerated, and risks worsening a
      metabolic disorder in the long term, to use a combination of hypotensive drugs.
      This should enable blood pressure control in 80 to 90% of cases, and improved
      acceptability, a major factor in treatment compliance. It is reasonable to hope,
      in the long term, that the use of a combination of lower doses than as
      monotherapy, will ensure less interference with major metabolic, endocrine and
      vascular functions, leading to a further improvement in the prognosis of treated
      hypertension.

PMID- 7825950
TI  - [Interventional cardiology. Indication of angioplasty].
AB  - Coronary angioplasty is currently a technique reaching its maturity. The
      technical perfection of balloons is such that increasingly complex coronary
      lesions are accessible, with a very high success rate. Approximately 30,000
      angioplasties are performed in France each year, France thus being the second
      country in Europe for the technique. While balloon angioplasty remains the
      standard technique, many others have developed. Among them, the rotatory auger or
      rotablator enables the removal of atheroma from the coronary vessel, thereby
      facilitating, in the case of calcified and complex lesions, the subsequent
      balloon procedure. Coronary stents have obviously modified the management of
      complications during angioplasty and lower the incidence of poor results of
      balloon coronary angioplasty. Extension of the indications of stenting appears to
      be fairly clear in the context of aortocoronary bypass, but is more open to doubt
      in the case of primary lesions. However, recent studies appear to suggest better
      long-term results following stenting. The weak point of these techniques remains
      restenosis and techniques of the future will be those which provide a perfect
      immediate result and avoid restenosis later. In this context, massive strides in
      molecular biology and gene therapy seem to be of major interest.

PMID- 7825951
TI  - [Coronary angioplasty, a privileged method of myocardial revascularization of the
      elderly].
AB  - Coronary angioplasty is a myocardial revascularisation technique of choice in the
      elderly, avoiding the need for general anesthesia as well as the complications of
      thoracotomy and extracorporeal circulation. Used in a continuous series of 62
      patients, it provided a 79% primary success rate in this situation, where
      reaching the coronary artery and penetrating the stenosis may be difficult.
      Femoral complications (hematoma, false aneurysm) are commoner in this age group,
      but appear to be beneficially influenced by the replacement of heparin by
      ticlopidine peri-operatively. With 24 months follow-up, the proportion of
      patients free of any major cardiac event and NYHA classes I and II is 66%,
      actuarial survival rate without infarction is 76%. These results would tend to
      restrict the indications for bypass after the age of 75 to cases of stenosis of
      the left main coronary artery, failure of angioplasty or multi-vessel atheroma
      with a "culprit lesion" inaccessible to dilatation.

PMID- 7825952
TI  - [Difficulties in the diagnosis of cardiac insufficiency in octogenarians].
AB  - The incidence of heart failure in octogenarians is high and its diagnosis not
      always easy. In many cases it is made by excess or by omission. Obtaining a
      history is often difficult. Signs may be masked, false or indicative of another
      disease process. Dyspnea, edema of the lower limbs and crepitations are
      relatively non-specific. Jugular distension, tender hepatomegaly and a diastolic
      gallop are much more valuable. Diagnosis of the underlying etiology also raises
      problems. While hypertension is commonplace and easy to identify, ischemic heart
      disease is common and often missed. Tight aortic stenosis must be identified
      since its treatment is surgical. Hypertrophic cardiomyopathy is often an
      echocardiographic discovery. Post-embolic chronic cor pulmonale, or secondary to
      chronic obstructive lung disease, must always be considered in the presence of
      right heart failure without hypertension or chest pain. Appropriate treatment is
      dependent upon accurate diagnosis.

PMID- 7825953
TI  - [Diagnosis, course and prognosis of pulmonary arterial hypertension].
AB  - Pulmonary arterial hypertension (PAHT) is defined by an increase in mean
      pulmonary artery pressure above 20 mmHg. Its diagnosis is often easy by cardiac
      echo-Doppler. Hemodynamic investigation is required in non-echogenic patients or
      in order to define the type of PAHT: pre- or post-capillary. It is important to
      determine, on the basis of non-invasive clinical and paraclinical
      (echocardiography) studies, those patients in whom catheterisation is indicated.
      PAHT may be due to chronic respiratory disease, left heart disorders, congenital
      heart disease or follow pulmonary embolism. It is sometimes apparently primary.
      The prognosis of PAHT depends upon its etiology: when PAHT is secondary to heart
      disease, it reflects worsening of the causative cardiac problem, which must be
      corrected. PAHT is a prognostic factor in chronic obstructive lung disease. The
      course is particularly grave in primary PAHT.

PMID- 7825954
TI  - [Interventional cardiology methods in the treatment of ventricular arrhythmia].
AB  - Sustained ventricular arrhythmias are the primary cause of sudden death in
      France. Treatment possibilities have increased in recent years with the
      development of interventional rhythmology techniques. Thus alongside the
      classical pharmacological approach, clinicians now have access to more aggressive
      treatment methods such as implantable pacing-defibrillation systems or
      endocavitary excision techniques. Implantable defibrillation systems are of
      proven efficacy in reducing ventricular arrhythmias but their action is merely
      palliative. Technological advances have simplified their implantation and
      increased their diagnostic and therapeutic abilities. Their high price is
      nevertheless one of the factors limiting their wider use in some countries.
      Endocavitary excision techniques, with a radical curative effects, are used only
      in cases of sustained monomorphous ventricular tachycardia in the absence of any
      associated cardiac surgery procedure. Coronary angioplasty is of rhythmological
      value when the etiopathogenesis of the arrhythmia is of proven ischemic origin.
      Rather than being competitors, these various methods are complementary, each
      having specific characteristics forming the basis of particular indications.

PMID- 7825955
TI  - [Evaluation of amlodipine in stable effort angina in office cardiologic
      practice].
AB  - A multicentre trial was undertaken in order to evaluate the therapeutic efficacy
      and ease of use of amlopidine in 1890 patients with stable effort angina.
      Involving prescribing conditions close to those of everyday practice, it revealed
      an improvement in angina symptomatology with one daily dose of amlopidine. After
      one month's treatment, 49.8% of patients were able to reduce or stop their use of
      fast-acting nitrites. After three months' treatment with amlopidine, 51% of
      patients had become asymptomatic. This study also revealed a decrease in the
      duration and severity of angina attacks. Safety/acceptability of amlopidine,
      assessed by clinical and laboratory parameters, was good, adverse events (22.7%),
      most often benign, improving or disappearing in more than half of all cases.

PMID- 7825957
TI  - Factors involved in clinical pharmacology variability in oncology (review).
AB  - One of the major problems in cancer pharmacology is the prediction of the outcome
      of treatment in terms of both toxicity and tumor response. Indeed, why is a
      patient presenting a high toxicity at a standard dose? Also, why is another
      patient presenting a response to chemotherapy, while another does not respond,
      even if the same doses and drugs are used? The causes of variability in the
      response to chemotherapy can be classified in 2 classes, these related to the
      host, and those related to the tumor. Concerning the host, physiopathological
      parameters can influence the outcome of treatment e.g. age, sex, kidney and liver
      functions, plasma protein binding, concomitant treatments, and pharmacogenetics.
      With regard to the tumor, many factors can also influence chemotherapy e.g. tumor
      type, localization, volume, aggressiveness, dissemination stage, prior treatments
      (resistance), biological marker levels, and pharmacogenetic phenotype. Although
      some progress has been made in the past years concerning the clinical use of some
      factors responsible for the variability of pharmacological response in oncology,
      much remains to be done in order to adapt the treatment to a particular patient.
      Although pharmacogenetic phenotyping has been feasible for some anticancer drugs,
      this area deserves more effort in the future. Indeed, pharmacogenetic phenotyping
      of both the patient and the tumor will probably allow to tailor chemotherapy to
      an individual patient, in order to optimize the patient's chances to obtain a
      tumor response with minimum systemic toxicity.

PMID- 7825958
TI  - Dose optimisation of carboplatin in adults.
AB  - Carboplatin haematological toxicities are clearly related to AUC. It seems likely
      that therapeutic efficacy is also related to AUC, although the maturation of
      clinical trials is necessary to establish this point. Using AUC-based dosing
      compensates for variations in renal function between and within individual
      patients. Since this variability is considerable, AUC-based dosing is a desirable
      practice. However, it does not allow for other factors such as previous
      chemotherapy, previous radiotherapy or performance status. Thus it does not
      remove the requirement for clinical judgements when managing a patient with
      cancer; it simply helps to remove one of the subjective elements of such
      judgements.

PMID- 7825956
TI  - Proceedings of the 5th Conference on Oncological Clinical Pharmacology. Reims,
      France, 8-10 November 1994.

PMID- 7825959
TI  - The comparative pharmacokinetics and pharmacodynamics of cisplatin and
      carboplatin in paediatric patients: a review.
AB  - Cisplatin and carboplatin are important drugs in the treatment of childhood
      cancers. Extensive data for carboplatin, and more limited results with cisplatin,
      indicate that there is significant inter-patient pharmacokinetic variability such
      that adaptive dosing may be necessary for the optimal use of these drugs.
      Glomerular filtration rate based dosing formulae have been developed for
      carboplatin and their use is reviewed. Further studies are needed with cisplatin
      in order to define the reasons for inter-patient pharmacokinetic variability and
      its relevance in clinical practice. Only very limited data are available on the
      clinical or molecular pharmacodynamics of cisplatin and carboplatin in paediatric
      patients. By analogy with adult studies, pharmacologically-guided platinum
      complex treatment should offer significant advances over empiric dosing.

PMID- 7825960
TI  - Comparison of two dose prediction models for cisplatin.
AB  - Cisplatin toxicity could be decreased by adjusting its dosage to each patient.
      For this purpose, a limited sampling method was established and validated based
      on a Bayesian approach taken using the values of assays during a 5-day continuous
      infusion of cisplatin. Using this method, a dosing model to achieve a target
      plasma concentration of total platinum (Pt) was evaluated retrospectively; the
      calculated dose of cisplatin was 95.0 to 104.8% of the actual dose. This model
      was then studied prospectively and the actual plasma Pt concentration reached at
      the end of the infusion was 94.9% of the target concentration. A strong
      correlation was observed between the clearance of Pt and the calculated clearance
      of creatinine or Cockroft index (p = 1.7 x 10(-11), and this correlation was used
      to develop another cisplatin dosing model. With this model the actual
      concentration reached at the end of the infusion was 85.3% of the theoretical
      concentration. The Bayesian approach gave reliable results for most clinical
      uses, whereas the creatinine based model has to be improved.

PMID- 7825961
TI  - Anticancer drug resistance and inhibition of apoptosis.
AB  - Apoptosis is a new concept which could be of great importance in the
      understanding and treatment of cancer. An important feature is the discovery of
      inhibitors of apoptosis, because they induce resistance to chemotherapeutic drugs
      and irradiation. Bcl-2 is the most well known of these apoptosis inhibitors. When
      it is overexpressed cells are less sensitive to cytotoxic drugs; on the contrary,
      when it is underexpressed they are more sensitive. Clinically, bcl-2 expression
      is associated with a poor prognosis in several cancers. Bcl-2 protein, p26-bcl-2,
      is located in the outer mitochondrial membrane, the nuclear envelope and the
      smooth endoplasmic reticulum. P26-bcl-2 is an antioxidant; this property could
      explain the anti-apoptotic activity since peroxides seem to be important
      mediators of apoptosis. Bcl-2 antisense oligonucleotides are able to reverse the
      apoptosis inhibition. New cancer treatments should take into account the
      expression of bcl-2.

PMID- 7825962
TI  - Dihydropyrimidine dehydrogenase (DPD) and clinical pharmacology of 5-fluorouracil
      (review).
AB  - Fluorouracil (FU) is essentially eliminated in the liver through the rate
      limiting enzyme dihydropyrimidine dehydrogenase (DPD). DPD is also expressed in
      various other normal as well as in tumor tissues. DPD activity measured in
      peripheral blood mononuclear cells (PBMC) is correlated to FU systemic clearance,
      but this correlation is weak, precluding PBMC-DPD to be considered as a reliable
      predictor of FU clearance. Nevertheless, patients with suspected or proven PBMC
      DPD deficiency exhibit severe FU-related toxicities. Population studies performed
      so far were unable to detect complete DPD deficient patients, suggesting that
      complete DPD deficiency is a very rare event; however 3% of patients exhibit a
      partial DPD deficiency indicative of increased risk for developing FU-related
      toxicity. Although FU resistance is multifactorial, DPD activity in tumor cells
      (in vitro and clinical studies) is significantly related to FU sensitivity: the
      lower the DPD activity, the greater the FU efficacy. Further prospective clinical
      studies will be required in order to confirm the present observations.

PMID- 7825964
TI  - Dose optimization of anthracyclines.
AB  - Despite the fact that anthracyclines are one of the most commonly used and active
      classes of anticancer agents and that their pharmacokinetic behavior has been
      extensively studied, optimal anthracycline dosage regimens have not yet been
      defined. Only a few pharmacokinetic-pharmacodynamic (toxicity and response)
      relationships have been determined so far for anthracyclines and are here
      reviewed. The use of prolonged continuous infusion and fractionated schedules
      reduces doxorubicin cardiotoxicity but no sufficient data are available to date
      to demonstrate if those schedules result in equivalent antitumor efficacy to that
      achieved by IV bolus. Not enough data are available to conclude which is the best
      pharmacokinetic parameter to use in order to predict anthracycline-induced
      myelosuppression, other toxicities and/or clinical tumor response. Dosing
      adjustments of anthracyclines in the presence of liver dysfunction are still
      based on empirical guidelines instead of a more rational basis. Much work still
      remains to be done if we are to improve our knowledge of anthracyclines'
      pharmacodynamics. Limited sampling strategies will be of great help in the
      establishment of pharmacokinetic-pharmacodynamic relationships, which is
      essential to optimize the dosage regimen of anthracyclines in order to maximize
      their efficacy and/or minimize their toxicity in individual patients.

PMID- 7825965
TI  - Concepts of synergism and antagonism.
AB  - Combinations of drugs or association of drugs with radiation are often envisaged
      using in vitro or in vivo models in order to find optimal combinations yielding
      the highest antitumor activity. The concept of synergism is not clearly
      established in vivo because of the necessity of considering both the antitumor
      activity, the toxicity and often the occurrence of unexpected side-effects. In
      vitro, several concepts have been proposed to surmount this problem and different
      attempts made to standardize the methodology and the terminology used when
      combination of anticancer agents is envisaged. In this paper, the main different
      methodologies used for the analysis of anticancer agent combinations--fractional
      product, isobole analysis, median-effect principle--are reviewed and the
      parameters limiting their respective applicabilities--linearity or linear
      transformability of the dose-response curves, mutual exclusiveness of the
      anticancer agents--are discussed.

PMID- 7825963
TI  - Dose optimization of gallium chloride, orally administered, in combination with
      platinum compounds.
AB  - An individual dose adaptation for cisplatin (CDDP), etoposide and gallium
      chloride (GaCl3) was proposed to improve the efficacy of this combination
      chemotherapy and avoid its toxicity. A clinical study was performed in 28 non
      small cell lung cancer patients, to verify this hypothesis. CDDP and etoposide
      were administered as continuous infusions every 3 weeks and GaCl3 orally during
      and between the CDDP-etoposide sequential infusions. CDDP doses were adjusted to
      achieve, during each 5 day infusion, an area under the total plasma platinum
      concentrations versus time curve (AUC Pt 0-120) ranging between 80,000 and
      100,000 micrograms/l.h. Etoposide dosages were 120 mg/24 h during days 1-3 of the
      CDDP infusion. GaCl3 dosages were adjusted to obtain plasma gallium (Ga)
      concentrations ranging between 200 and 400 micrograms/l. The proposed methods of
      adaptation were successful from a pharmacokinetic point of view as AUC Pt 0-120
      were respectively 81351 +/- 4788, 88268 +/- 8451 and 88331 +/- 8778
      micrograms/l.h during the first 3 courses, and plasma Ga concentrations,
      determined during the 2nd and 3rd CDDP courses, 16 hours after the beginning of
      the CDDP infusion, were respectively 264 +/- 127 and 313 +/- 186 micrograms/l.
      However, these results were not pharmacodynamically successful and the
      therapeutic window was not confirmed. Past clinical trials with GaCl3 will be
      reviewed, as well as the factors which modify the pharmacokinetics or the
      pharmacodynamic effects of CDDP and GaCl3. From this review, an optimal dosage of
      400 mg GaCl3 could be proposed to potentiate a combination chemotherapy with a
      platinum compound. The target AUC of the platinum compound should be the AUC
      avoiding its cumulative toxicity.

PMID- 7825966
TI  - Population kinetics and conditional assessment of the optimal dosage regimen
      using the P-PHARM software package.
AB  - The adjustment of individual dosage regimen is an adaptive control process based
      upon an individual response to a pharmacokinetic model. To attain this objective,
      it is very helpful to know the characteristics of the population to which the
      subject belongs, in terms of mean parameters and interindividual variability.
      Usually the available information consists of incomplete and sparse data. For
      this reason it is essential to employ a computational methodology based on non
      linear mixed-effect procedures in order to obtain a population parameter
      estimate. A Bayesian methodology can then be applied from the population
      parameters to the specific data for the individual requiring a dosage adjustment
      (such data includes drug concentration(s) of the active drug, demographic data,
      etc). The result of the Bayesian calculation supplies the required individual
      pharmacokinetic parameters. An optimal dosage regimen can be defined on the basis
      of therapeutical criteria (concentration ranges) as well as practical constraints
      such as: the size of available unitary drug dosages, feasible drug intake times,
      penalties associated with expected concentrations falling outside the therapeutic
      concentration ranges. In this paper we present the methodology and results
      obtained using the P-Pharm software tool. P-Pharm implements a non-linear mixed
      effect population parameter estimation algorithm based on the EM algorithm. This
      method allows the inclusion of explicit variables into the calculations, it
      implements an individual Bayesian parameter estimation procedure and also an
      algorithm for the conditional assessment of the optimal dosage regimen given a
      list of practical constraints.

PMID- 7825967
TI  - Pharmacokinetic study in carboplatin, cisplatin and 5-fluorouracil regimen for
      advanced oesophageal cancer.
AB  - A chemotherapy using carboplatin, cisplatin and 5-fluorouracil in continuous
      infusion for advanced oesophageal cancer showed a high response rate in a
      previous feasibility study. The overall CT-scan response rate of 85% was obtained
      with a haematological dose-limiting toxicity: neutropenia and thrombopenia grade
      3-4 of 23% and 30% respectively. In order to correlate myelosuppression with
      pharmacokinetic parameters, a pharmacological study was undertaken. The area
      under curve (AUC) of ultrafiltrable platinum and the residual rate of total
      platinum in 16 patients were tested. The measured creatinine clearance was found
      to be predictive of the subsequent myelosuppression. Plasma samples were using
      daily using the atomic absorption spectrometry technique. A strong relationship
      in individual patients was underlined between the AUC of ultrafiltrable platinum
      or residual rate of total platinum and the lowest platelet count for the first 3
      days of treatment (p < 0.05). Conversely, the threshold value of the AUC at day
      one and residual rate at days two and three were calculated to prevent a highly
      probable haematotoxicity. Therefore, an optimal dose of carboplatin is determined
      in relation to the renal function of each patient.

PMID- 7825968
TI  - Culture conditions modulate the effects of aclacinomycin A on growth,
      differentiation and apoptosis of HL60 cells.
AB  - The continuous incubation for several days of HL60 cells, in exponential growth,
      with aclacinomycin A (ACM) induces growth inhibition, necrosis, differentiation
      and apoptosis. Differentiation and apoptosis were assessed by optical microscopy
      (OM) and flow cytometry (FCM). ACM displayed dose-dependent effects, except for
      the differentiation induction, which was biphasic. Differentiation and apoptosis
      could also be induced after a 1 h ACM exposure only. The poor reproducibility of
      apoptosis induction led us to study the culture conditions described in the
      literature (without renewing the medium) where control cells are not growing
      exponentially during the 5 day incubation period. During kinetic studies with
      different ACM concentrations, the differentiation was detected earlier by FCM
      than by OM, while it was not the case for apoptosis. This induction appeared more
      reproducible when non optimal conditions of culture were used.

PMID- 7825969
TI  - Retinoids and differentiation treatment: a strategy for treatment in cancer.
AB  - The retinoids are a large group of compounds structurally related to vitamin A.
      Retinoids elicit specific biological responses by binding to and activating
      nuclear receptors. Information about the metabolism and storage of vitamin A and
      retinoids, their plasma transport and uptake and the retinoid dose efficient on
      target cell had to be established because retinoic acid (RA), the natural acidic
      derivative of vitamin A (retinol), is likely to be a key factor during specific
      phases of embryonic development and maintenance of normal differentiated
      phenotypes in adult, so vitamin A is involved in the normal morphological
      differentiation of the visual system. RA appears an important agent since it
      induces in vitro leukemic cells from acute promyelocytic leukemia (APL) to
      differentiate into mature functional granulocytes which lose their self-renewal
      ability and die spontaneously. In vivo, APL patients treated with oral all-trans
      retinoic acid (all-trans RA) alone achieve complete remission in 80% of the
      cases. APL results from a malignant process that leads to the accumulation in the
      blood and in the bone marrow of myeloid precursor cells characterized by an
      abnormal behavior and a differentiation arrest. APL is characterized
      cytogenetically by a t(15;17) translocation which involves both the PML gene on
      chromosome 15 and the RARa gene on chromosome 17 and gives rise to the PML/RARa
      fusion protein. The high sensitivity of the promyelocytic blasts to all-trans RA
      should be related to the presence in APL blast of an abnormal protein, the
      PML/RAR alpha. The antineoplastic effects of retinoids suggest that these drugs
      could be used therapeutically for the chemoprevention of cancer.

PMID- 7825970
TI  - Clinical randomized study of 5FU monitoring versus standard dose in patients with
      head and neck cancer: preliminary results.
AB  - Prospective studies of dose adaptation of continuous 5FU infusion combined with
      cisplatin have shown that pharmacologically guided dosing was feasible in the
      treatment of head and neck carcinomas. Adaptative dosing results in reduced
      haematological toxicity, but few data are available for clinical response rate.
      Preliminary results (38 patients) of a randomized trial comparing standard dose
      of 5FU (20 patients) and monitoring of 5FU based on pharmacokinetic information
      (half-cycle area under the curve, 18 patients) indicate that haematological
      tolerance and complete response rate were improved. Severe (GIII-GIV)
      thrombocytopenia and neutropenia were significantly reduced during cycle 2 (0%
      versus 11.1% and 5.5% versus 27.7% respectively, p < 0.01) and cycle 3 (0% versus
      27.7% and 6.6% versus 33.3% respectively, p < 0.001). The complete response rate
      was increased in the group with monitoring of 5FU doses (55.5% versus 40.0%, p <
      0.001). These interesting results will be confirmed at the end of the trial,
      which is expected to include 126 patients.

PMID- 7825971
TI  - Binding of anthracycline derivatives to human serum lipoproteins.
AB  - The binding of eight anthracycline analogues (including mitoxantrone) to isolated
      serum lipoproteins (high, low and very low density lipoproteins) was studied in
      order to elucidate some determinants of their interaction with lipidic
      structures. Serum lipoproteins were isolated by ultracentrifugation. Drug binding
      experiments were run by ultrafiltration at 37 degrees C and pH 7.4. Anthracycline
      concentrations (total and free) were determined by HPLC with fluorometric
      detection. All the ligands were significantly bound to the three lipoprotein
      classes, and for each ligand the binding increased as the lipidic fraction of
      lipoprotein increased. From doxorubicin to iododoxorubicin, there was a tenfold
      increase in lipoprotein binding (doxorubicin < mitoxantrone < epirubicin <
      daunorubicin < pirarubicin < aclarubicin < zorubicin < iododoxorubicin). For all
      the ligands studied, the extent of lipoprotein binding appears to be related to
      chemical determinants of lipophilicity.

PMID- 7825972
TI  - Concomitant chemotherapy and radiotherapy: theoretical basis and clinical
      experience.
AB  - Combined radiotherapy and chemotherapy can be used in order to improve control
      and survival rates of solid tumors A concomitant radio-chemotherapy schedule
      optimizes interactions between chemotherapy and radiotherapy compared to a
      sequential approach. Experimental data try to explain these interactions at
      tissular, cellular or molecular levels. Cisplatin, 5 FU, mitomycin C, etoposide
      and hydroxyurea are particularly efficient to sensitize radiation treatment in
      order to obtain a supra-additive effect. Therapeutic gain without excess of
      toxicity should be the aim of clinical trials. This goal may have been achieved
      for some tumors, specially for oesophageal, rectal, pancreatic and anus cancer.
      For other tumors (head and neck, lung, bladder, uterine, cervix and gastric
      cancer) there is strong experimental and clinical support to continue this
      approach by clinical trials.

PMID- 7825973
TI  - Pharmacologically-guided dose adjustment of busulfan in high-dose chemotherapy
      regimens: rationale and pitfalls (review).
AB  - High-dose busulfan is used in conditioning regimens before allogeneic or
      autologous bone marrow transplantation (BMT) in adults and children. During the
      last six years, several studies have established the wide inter- and intrapatient
      variability of high-dose busulfan disposition. Clearance rate ranges from 0.8 to
      20 ml/min/kg. Some factors of variability have been identified: age, alteration
      in hepatic functions, disease, circadian rhythmicity, drug interactions. Using a
      fixed dose of busulfan, wide interpatient variability in systemic exposure is
      thus expected, with eventual consequences on toxicity and efficacy. In adults, a
      pharmacodynamic relationship between a high busulfan systemic exposure and the
      occurrence of hepatic veno-occlusive disease (HVOD) has been established. A
      prospective controlled study demonstrated that busulfan dose-adjustment decreased
      the morbidity and mortality of HVOD in adults. So far, pharmacodynamic studies in
      children have failed to establish a toxic level. The present paper analyses the
      rationale for busulfan dose adjustment, and focuses on the eventual pitfalls that
      may jeopardize its reliability (drug absorption, chronopharmacology, drug
      interaction within the conditioning regimen, complex pathophysiology of HVOD).
      Further pharmacodynamic studies are required to establish a minimum therapeutic
      threshold in systemic exposure for bone marrow engraftment, especially in
      children undergoing HLA-compatible or incompatible allogeneic BMT for non
      malignant disease. The definition of a therapeutic window according to the
      disease and the type of BMT, along with the development of iv-busulfan, will
      allow accurate and effective pharmacologically-guided dose adjustment of high
      dose busulfan. By the end of the century, busulfan plasma level monitoring and
      dose adjustment at the individual level may improve the outcome of patients
      undergoing BMT.

PMID- 7825974
TI  - Proposals for concomitant use of several modulators of multidrug resistance in
      clinics.
AB  - Numerous modulators of multidrug resistance present a good in vitro activity
      which has not always been reproduced in vivo or in clinics. One reason is the
      fact that the plasma concentration required might exceed the maximum tolerated
      dose of modulator, due to its own toxicity. In addition, it has been suggested
      that the different modulators thus far identified might act on different sites of
      P-glycoprotein and eventually on different targets. It has been shown that the
      combination of verapamil and quinine, and of verapamil and cyclosporine A, behave
      synergistically in the circumvention of multidrug resistance. There is therefore
      a good rationale for the evaluation of protocols combining two different
      modulators to cytotoxic chemotherapy.

PMID- 7825975
TI  - KINFIT: a non linear least-squares computer program for the estimation of
      pharmacokinetic parameters after intravenous administration.
AB  - KINFIT is a nonlinear least-squares computer program designed to allow
      pharmacokinetic modeling of experimental data and to obtain pertinent parameter
      estimates based on the derived values. It is written in Visual BASIC for the
      Microsoft Windows graphical environment. Drug concentrations in blood, plasma, or
      serum with time following intravenous administration are input and a linear or
      semi-logarithmic plot of the data appears on the display. On command,
      polyexponential coefficients and exponents are computed and a non linear curve is
      fitted through the data set. Results from statistical tests are printed to
      determine goodness of fit. Commonly calculated pharmacokinetic parameters are
      also calculated and appear on the output. The execution of KINFIT is demonstrated
      for time courses of ampicillin in man. KINFIT was compared with the widely
      available ESTRIP and RSTRIP computer programs and gave parameter estimates that
      were very similar, although not identical.

PMID- 7825976
TI  - Pharmacokinetics of high-dose melphalan in adults: influence of renal function.
AB  - BACKGROUND: The pharmacokinetics of melphalan were studied in 20 patients with
      multiple myeloma, primary amyloidosis or lymphoma after IV dose of 140 mg/m2
      infused over 30 minutes (two patients were treated with a higher dose). MATERIALS
      AND METHODS: Six patients received melphalan alone, 8 received melphalan combined
      with total body irradiation, 2 received busulphan plus melphalan and 4 received
      the BEAM association (BCNU + etoposide + high dose aracytine + high dose
      melphalan). Creatinine clearance was measured immediately before the infusion of
      melphalan, and 9 blood samples were taken to monitor elimination kinetics.
      RESULTS: Pharmacokinetic parameters (CIT, Vdss, t1/2) and areas under the curve
      (AUC) were comparable to those obtained by Ardiet et al after rapid IV injection.
      For all patients, AUC, CIT, Vdss, t1/2 beta and MRT were significantly correlated
      with creatinine clearance; the different pharmacokinetic parameters calculated
      showed great interindividual variations. CONCLUSIONS: Renal insufficiency did not
      lead to a large decrease in melphalan clearance compared to interindividual
      variations in systemic clearance.

PMID- 7825977
TI  - Study of sodium orthovanadate as a reverser of multidrug resistance on
      lymphoblastic leukemic CEM/VLB100 cells.
AB  - The occurrence of multidrug resistance (MDR) is the major cause of failure of
      cancer chemotherapy. Finding a way to circumvent this problem is now a major
      challenge in oncology. Multidrug resistant CEM/VLB100 cells accumulate 10 times
      less vinblastine (VLB) after 30 min than their sensitive counterparts (CEM
      cells). At a non-cytotoxic concentration (1 mM) of sodium orthovanadate (OVN),
      uptake by CEM/VLB100 cells was increased 4 times while no effect was observed on
      CEM cells. The action on VLB uptake of OVN and verapamil (VPL), an usual MDR
      modulator, was additive. In CEM/VLB100 cells, OVN did not alter efflux. Its
      cellular mechanism of action could involve a transitory stimulation of VLB influx
      (x3). OVN uptake in CEM and CEM/VLB100 cells was not significantly different and
      reached saturation after 30 s (180 pmol/10(6) CEM cells and 150 pmol/10(6)
      CEM/VLB100 cells). This OVN uptake was concentration dependent. IC50 of VLB and
      doxorubicin were decreased by approximately 43 and 62% after 1 hour's exposure to
      OVN and 48 hours of culture. Under these conditions, OVN was more efficient than
      OVN.

PMID- 7825978
TI  - Effect of S9788, cyclosporin A and verapamil on intracellular distribution of THP
      doxorubicin in multidrug-resistant K562 tumor cells, as studied by laser confocal
      microspectrofluorometry.
AB  - S9788 modulating resistance effect has been investigated on the activity of THP
      DOX against multidrug-resistant K562R cells and compared to that of cyclosporin A
      and verapamil. Intracellular THP-DOX distribution and particulary its
      intranuclear concentration, with or without modulators, has been measured using
      confocal laser microspectrofluorometry. The kinetics of intranuclear accumulation
      of THP-DOX (1 microM in the medium), as a function of time, were rapid in K562S
      and K562R cells. Maximum accumulation of THP-DOX is reached in a few minutes
      (K562S, 400 microM; K562R, 40 microM). The addition of S9788, cyclosporin A and
      verapamil (5 microM) after one hour THP-DOX incubation, led to respectively 290,
      250 and 114 microM. Uptake of THP-DOX was increased in K562R cells by a factor of
      7 when S9788 was added. Results obtained on THP-DOX efflux from nuclei of K562S
      and K562R cells, after 3 hours of incubation without drug, showed a very short
      T1/2 (time corresponding to 50% decrease of intranuclear concentration of THP
      DOX) in K562R cells (12 min) compared to that in K562S cells (150 min). The
      addition of S9788, cyclosporin A and verapamil (5 microM) led to a T1/2 of 90, 30
      and 20 min respectively. The T1/2 of THP-DOX was increased in K562R cells by a
      factor of 7.5 when S9788 was added. We tried to correlate these results with
      those obtained in growth inhibition study. The IC50 (concentration which induces
      50% growth inhibition) of THP-DOX, corresponding to one hour THP-DOX treatment
      and 3 days culture of K562S and K562R cells were respectively 230 and 7000 nM,
      and the RI (resistance index) value is 30. The addition of S9788, cyclosporin A
      and verapamil (5 microM), during the one hour treatment, led to an IC50 value of
      350, 2000 and 5000 nM respectively. S9788 induced an IC50 value 20 times lower
      than without the modulator. Our study suggests that the higher activity of THP
      DOX against K562R cells in the presence of S9788, compared to cyclosporin A and
      verapamil, is due to a higher intranuclear THP-DOX accumulation and to a strong
      decrease of drug efflux from K562R nuclei. This could be explained by a higher
      affinity of S9788 for membrane P-glycoprotein of K562R cells and/or an additional
      mechanism of action.

PMID- 7825979
TI  - Pharmacodynamics of 5-fluorouracil combined with carboplatin in patients with
      head and neck cancer.
AB  - The objective of our work was to investigate the pharmacodynamics of 5
      fluorouracil (5-FU) in 23 patients with head and neck cancer treated with
      carboplatin (360 mg/m2) followed by 5 day continuous infusion of 5-FU
      (lg/m2/day). The pharmacokinetic profile of 5-FU was characterized for 36 cycles
      and was compared with the patient's tolerance. Toxic cycles (> or = grade 1, WHO
      grading) were associated with higher values of area under the serum concentration
      time curve (AUC) than those of non toxic cycles. In addition, AUC values of 37000
      ng.h.ml-1 and 21000 ng.h.ml-1 for the entire cycle and the half-cycle
      respectively were found to be predictive of toxicity. These threshold values are
      identical to those determined in our previous study with the cisplatin-5-FU
      regimen. Hence, patients treated with carboplatin and infusional 5-FU might
      benefit from 5-FU blood level, monitoring using the same dose adjustment diagram.

PMID- 7825981
TI  - [Nephrectomy in children. Apropos of 55 cases].
AB  - Based on a series of 55 children undergoing nephrectomy, the authors describe the
      clinical, laboratory, radiological, therapeutic and prognostic features for each
      aetiology. They define the criteria for resection of the affected kidney.

PMID- 7825980
TI  - [The role of corticotherapy and endoscopy in the treatment of urogenital
      tuberculosis].
AB  - Despite the efficacy of new tuberculostatic agents, urogenital tuberculosis still
      constitutes a threat to renal function due to fibrosis secondary to healing of
      the lesions. The authors studied the place of corticosteroids, and endoscopic and
      percutaneous procedures in the treatment of 86 cases of urogenital tuberculosis.
      Corticosteroids were coprescribed with tuberculostatic agents in 20 patients: 16
      ureteral strictures were treated with 8 success and 8 failures, 8 contracted
      bladders were treated with 5 success and 3 failures. Three cases of retraction of
      the renal pelvis were treated by corticosteroids with 2 successes and one
      failure. Ureteral stricture was treated by retrograde ureteral stenting in 5
      cases and by percutaneous antegrade ureteral stenting in one case with 4
      successes and 2 failures. This study more clearly defines the indications for
      corticosteroids and endoscopic treatment with particular reference to new
      endoscopic surgery techniques.

PMID- 7825982
TI  - [Pathological horseshoe kidney. Therapeutic aspects].
AB  - The authors report the various therapeutic modalities of uropathies associated
      with horseshoe kidney, based on a series of 20 pathologic horseshoe kidneys,
      associated with 12 cases of renal stones, 5 ureteropelvic junction obstructions,
      3 kidney tumors, 2 cases of pyonephrosis and finally 1 traumatic horseshoe
      kidney. The specific anatomic and surgical features of this uncommon malformation
      are emphasized and the therapeutic features of each uropathy associated with
      horseshoe kidney are discussed.

PMID- 7825983
TI  - [Perirenal urinoma].
AB  - A urinoma is an encapsulated extravasation of urine which can be secondary to
      trauma or which can occur spontaneously. The essential factors are continued
      renal function, rupture of the collecting system and distal obstruction. The
      extravasated urine causes lipolysis and stimulates an intense fibrous reaction
      which forms a thick wall. This lipolysis may be due to a mass effect as no direct
      effect of the urine on adipocytes has ever be demonstrated. Early diagnosis by CT
      scan allows easier treatment: in certain cases, percutaneous drainage alone may
      be sufficient.

PMID- 7825984
TI  - [Does vitamin E protect against experimental lithiasis?].
AB  - We have recently suggested that vitamin A could protect against experimental
      lithiasis by repairing tubular membrane cells or protection against membrane
      damage caused by free radicals generated during experimental lithiasis. Although
      vitamin E treatment demonstrated no beneficial effect on stone formation, it
      promoted the repair mechanism by vitamin A during experimental lithiasis and by
      supported the hypothesis that oxalate crystals may be destructive to renal
      epithelium because they are large and irregular.

PMID- 7825985
TI  - [Bladder tumors in patients under 40 years of age].
AB  - A total of 13 patients under the age of 40 years were treated for bladder
      carcinoma. One child had a bladder sarcoma. 8 patients had a superficial
      transitional cell carcinoma with no evidence of recurrence after endoscopic
      resection. Four patients had invasive bladder carcinoma. Superficial bladder
      carcinoma would appear to have a good prognosis in patients under 40 years of
      age.

PMID- 7825986
TI  - [Longitudinal division of the penis caused by an indwelling urinary catheter in a
      paraplegic patient].
AB  - The authors report a rare case of longitudinal section of the penis, due to an
      urethral catheter. The patient was paraplegic and schizophrenic. They found only
      six such cases in the literature. They stress the risk of such complications in
      psychiatric patients.

PMID- 7825987
TI  - [Bilateral testicular metastasis of an adenocarcinoma of the prostate].
AB  - Secondary testicular tumors are very rare. Since 1935, approximately 200 cases
      have been documented in the international literature. Testicular metastases of
      prostatic carcinoma are reported more frequently and other common primary tumor
      sites are the lung, kidney, colon, stomach and other sites. A review of the
      literature revealed 43 cases originating from prostatic carcinoma with 4
      bilateral cases. The authors add a rare case of bilateral metastasis to the
      testis originating from prostatic carcinoma. This patient had been treated by
      transurethral resection of the prostate and bilateral orchidectomy 24 months
      previously.

PMID- 7825988
TI  - [Male internal pseudohermaphroditism or a man with a uterus].
AB  - Mullerian structures were discovered during cure of bilateral ectopic testes in a
      14-year-old boy. The original feature of this case was the presence of both
      testes on the same side. The Mullerian structures were left in place as they were
      intimately adherent to the vas deferens. This attitude was adopted as no
      degeneration of these structures has been described and because of the
      possibility of reproduction of these patients during adulthood.

PMID- 7825989
TI  - Placental transfer of tetanus toxoid antibodies in Nigerian mothers.
AB  - The aim of this study was to assess the efficacy of the tetanus toxoid
      immunization programme in Nigeria, specifically the placental transfer of
      antibody to newborn Nigerian babies. Tetanus toxoid antibody levels were measured
      in 39 mother-baby pairs in Ibadan, Nigeria and compared with 78 British mother
      baby pairs. Geometric means of the ratios of cord/mother (sequestration index SI)
      were 0.776 for Nigerian pairs and 1.306 for British pairs, indicating a
      limitation in the placental transfer of tetanus toxoid in the Nigerian
      population. These findings confirm that there is a block in the placental
      transfer of anti-tetanus toxoid antibodies in African populations which will
      affect current immunization programmes and requires further investigation.

PMID- 7825990
TI  - The immunogenicity and safety of Haemophilus influenzae type b-tetanus toxoid
      conjugate vaccine in Gambian infants.
AB  - In developing countries, Haemophilus influenzae type b is a major cause of
      meningitis and pneumonia in the 1st year of life. The safety and immunogenicity
      of a Haemophilus influenzae type b polysaccharide-tetanus toxoid conjugate
      vaccine (PRP-T) were evaluated in two studies of Gambian infants. In the first
      study, 131 infants were recruited and randomized into three groups to receive PRP
      T at 1 and 3 months (group A), PRP-T at 2 and 4 months (group B) or no PRP-T
      (group C). The liquid form of PRP-T was used. The geometric mean titre (GMT) of
      anti-PRP antibody 1 month after the second dose was 0.26 microgram/ml in group A
      and 0.41 microgram/ml in group B. In the second study, 66 infants were given PRP
      T in the lyophilized form at 2, 3 and 4 months of age. The GMT 1 month after the
      first dose was 0.09 microgram/ml, after the second 0.74 microgram/ml and after
      the third 2.32 micrograms/ml. After the third dose, 72% of children had antibody
      levels greater than 1.0 microgram/ml and 93% greater than 0.15 microgram/ml. No
      serious side-effects were observed and the rate of adverse reactions was
      consistent with the concurrent administration of diphtheria-tetanus-pertussis
      (DPT) vaccine.

PMID- 7825991
TI  - Cystic fibrosis and the liver--a Saudi experience.
AB  - Cystic fibrosis (CF) is an autosomal recessive disorder that is reported
      frequently among Caucasians. In view of the high rate of consanguinity in Saudi
      Arabia and the high number of children dying so young, many Saudi infants with CF
      remain undiagnosed owing to lack of clinical suspicion and proper diagnostic
      facilities. Over a 6-year period (1986-1992), we have made a diagnosis of CF in
      36 cases. The aim of this report is to increase awareness of the hepatic
      presentation of CF in the developing word. Nine patients (25%) were originally
      referred to us as having liver disorders but subsequent investigations confirmed
      the diagnosis of CF. The referral diagnoses, number of patients in parentheses,
      were jaundice for investigation (four), glycogen storage disease (three),
      hepatomegaly for investigation (one) and neonatal hepatitis (one). Liver
      biopsies, obtained in five cases, demonstrated portal fibrosis and some
      steatosis. Consanguinity was present in eight cases, two were siblings. Four
      patients died. Three families had previously lost seven siblings during infancy
      with clinical features consistent with CF. It is concluded that hepatic
      presentation among Saudi patients with CF is relatively common, with serious
      sequelae.

PMID- 7825992
TI  - Glucose-6-phosphate dehydrogenase, hexokinase and pyruvate kinase activities in
      erythrocytes of neonates and adults in Basrah.
AB  - The mean activities (95% confidence interval; number of patients) for erythrocyte
      glucose-6-phosphate dehydrogenase (G6PD), hexokinase (HK), and pyruvate kinase
      (PK) in haemolysate of clinically normal neonates from Basrah, Iraq were found to
      be 3.29 (0.10; n = 456), 0.61 (0.02; n = 219), and 5.10 (0.07; n = 500),
      respectively, all expressed as U/10(10) RBC at 37 degrees C. Comparative values
      for apparently healthy adults were: 2.14 (0.06; n = 186), 0.41 (0.02; n = 46),
      and 3.61 (0.07; n = 243). Differences between sexes in the mean activities of
      each of the three enzymes were not significant (p > 0.5), being several times
      less than the corresponding 95% confidence intervals. However, differences were
      highly significant between neonates and adults (p < 0.001), presumably reflecting
      the greater proportion of 'young' cells and/or their programming for higher
      activity in cord blood. The neonate-adult difference (95% confidence interval)
      for each enzyme was: G6PD, 1.15 (0.43); HK, 0.20 (0.14); and PK, 1.49 (0.64).
      Some degree of G6PD-deficiency was observed in 7.9% of male and 9.7% of female
      neonates, whereas the frequency in adults was 9.2% and 11.8% for males and
      females, respectively. The higher frequency in females accords with expectations
      based on gene frequency estimations.

PMID- 7825993
TI  - The Butajira Rural Health Project in Ethiopia: a nested case-referent (control)
      study of under-5 mortality and its health and behavioural determinants.
AB  - The associations between under-5 mortality and its health and behavioural
      determinants were investigated in a rural district of Ethiopia, by means of a
      concurrent case-referent technique nested within a study-base population
      established in 1987. Three-hundred and six infant and child deaths registered
      over a period of 1 year, were contrasted with 612 controls, matched for age, sex
      and study area. Data were collected by trained non-medical workers using a
      structured questionnaire. Breastfeeding and supplementary feeding came out as
      strongly protective against under-5 mortality, even when controlling for parental
      and environmental determinants. Early termination of breastfeeding was
      demonstrated to have a substantial impact on mortality, particularly on that
      caused by diarrhoea. Late introduction of supplementary feeding, particularly of
      protein origin, was also associated with increased under-5 mortality. When the
      relative impacts of parental, environmental and behavioural determinants are
      compared, the greater impact of parental factors can be demonstrated, especially
      among infants.

PMID- 7825994
TI  - Childhood febrile seizures (Benin City experience).
AB  - About 20% of children admitted during the study period had febrile convulsions,
      of which 5% were aged below 5 months or above 5 years. The study confirms the
      view that there is a strong familial predisposition in febrile seizures. Major
      causes of the rise in temperature in those studied included malaria, which
      accounted for 32.7%, followed by bronchopneumonia (16.8%), measles (15.4%),
      otitis media (13.4%) and tonsillitis (10.5%). The morbidity and mortality could
      be attributable to the socio-cultural background of the community which practices
      modes of therapy that are often detrimental to the health of patients.

PMID- 7825995
TI  - Diarrhoea among children in rural Somalia. Maternal perceptions, management and
      mortality.
AB  - Diarrhoea was the second most common symptom of disease in a longitudinal study
      of 431 children under 5 years of age in rural Somalia. Most mothers perceived
      diarrhoea as a condition in which oral rehydration therapy (ORT) and feeding were
      logical parts of its management. During 1 year of observation, ORT was used in
      the household in one-third of the episodes of diarrhoea, mostly by non-farming,
      young and literate mothers. Infants were treated more often than older children,
      as were also children in smaller households. In a 3-year demographic surveillance
      in the same area (1219 person years), the under-5 mortality from diarrhoea in
      children of literature and illiterate mothers was 43 per 1000 (95% CI 0-84) and
      93 per 1000 (95% CI 60-101), respectively. The findings suggest that the use of
      ORT is associated with a mother's ability to allocate time to health care and her
      general position in the household.

PMID- 7825996
TI  - Seasonality of rotavirus infection in Ghana.
AB  - Human rotavirus (HRV) infection and its seasonal distribution was studied over a
      12-month period in Ghana. A total of 561 stool samples, 447 diarrhoea stools and
      114 non-diarrhoea stools (controls), were obtained from children attending three
      polyclinics in Accra. Rotavirus was detected during 10 of the 12 months and
      showed a seasonal trend. It was high during the relatively cool dry months and
      low during the wet season. Peaks of infection were in February (26.2%) and
      September (24.5%). HRV was detected in 67 of 447 of the diarrhoea stools (15.0%)
      and in eight of 114 controls (7.0%). The HRV isolation rate was highest (20.2%)
      in the under-18-months age group. The RNA electropherotype of the HRV isolates
      was predominantly (83.6%) of the long type. Non-group A HRV was detected in 14.9%
      of the HRV-positive samples.

PMID- 7825997
TI  - Haemorrhagic disease in newborn and older infants: a study in hospitalized
      children in Kelantan, Malaysia.
AB  - This is a retrospective study of the epidemiology, clinical features, laboratory
      findings, treatment and outcome of haemorrhagic disease in 42 Kelantanese infants
      who were admitted to Hospital Universiti Sains Malaysia during a 2-year period
      (1987-1988). Classical haemorrhagic disease of the newborn was the commonest
      presentation (48%), followed by early onset (29%) and late onset (24%) disease.
      Home deliveries accounted for 81% of the affected infants. Most of these babies
      were not given vitamin K at birth in contrast to those delivered in hospitals.
      All except one infant were breastfed. The six commonest presenting clinical
      features were pallor, jaundice, umbilical cord bleeding, tense fontanelle,
      convulsions and hepatomegaly. All the infants had prolonged prothrombin and
      partial thromboplastin times which were corrected by administration of vitamin K.
      Subdural haemorrhage was the commonest form of intracranial haemorrhage, followed
      by subarachnoid haemorrhage. The overall case fatality rate was 14%. The results
      of this study once again emphasize the value of vitamin K prophylaxis in the
      newborn.

PMID- 7825998
TI  - High dose methylprednisolone therapy in children with onyalai.
AB  - Methylprednisolone at 30 mg/kg i.v. for 3 days followed by 20 mg/kg for 4 days
      was given to eight children who had been referred to Windhoek State Hospital with
      onyalai. The history of previous attacks, change in platelet count over 7 days,
      blood transfusion requirement and length of clinical bleeding were compared with
      similar parameters in a historical control group of 21 untreated children who had
      been observed in hospital. All the treated patients demonstrated a rise of at
      least 25 x 10(9)/l in the platelet count and the mean count increased from 16 x
      10(9)/l on admission to 161 x 10(9)/l on day 8. In the untreated control group,
      38% of children did not demonstrate a rise in platelet count of 25 x 10(9)/l (p <
      0.05) and the mean platelet count increased from 21 x 10(9)/l to 100 x 10(9)/l on
      day 8. The average duration of bleeding was 3.1 days in the controls versus 1.5
      days in the treatment group. One-third of the children in both groups needed a
      blood transfusion. Total blood use amounted to 0.9 unit per child for controls
      and 0.5 unit per child in the treatment group. The average cost of treatment
      (drug only) was $US 44 per patient. High dose methylprednisolone therapy reduced
      the morbidity of onyalai in children in this series.

PMID- 7825999
TI  - Presenting features of bacterial meningitis in young infants.
AB  - More guidance is required in the management of acutely ill, febrile young
      infants. Of 94 young infants undergoing lumbar puncture (LP) as part of their
      management, 26 of the 60 (43.3%) presenting with seizures and fever and six of
      the 34 (17.7%) without seizures had bacterial meningitis (BM) (relative risk (95%
      confidence interval) = 2.46 (1.12, 5.37), p = 0.012). Except for the presence of
      a bulging fontanelle and focal seizures, no other presenting signs or symptoms
      were significantly associated with BM; seven of the 26 infants with BM who
      presented with seizures and two of the six without seizures lacked a bulging
      fontanelle. Overall, the ratio of BM to other illnesses was 1:1.94; of those with
      BM, 13 of the 32 (40.6%) had co-existing acute respiratory infections and four of
      the 32 (12.5%) had asexual malaria parasitaemia. Seizures with fever are an
      important presenting feature of BM in young infants and a screening LP should be
      considered mandatory to confirm or exclude BM in febrile young infants with
      seizures, unless certain contraindications apply.

PMID- 7826000
TI  - A rare association of myelomeningocele with cloacal duplication malformation.
AB  - A Jordanian baby girl, born prematurely at 36 weeks gestation, was found to have
      myelomeningocele associated with duplication of the rectum, urinary bladder,
      ureters and vagina. This is most likely to have resulted from duplication of the
      cloaca during early development. The case demonstrates that duplication of the
      cloaca, albeit rate, may occur in combination with major malformations of the
      neural tube. Also, the question is raised as to whether or not this is a
      modification of the VACTERL syndrome since the child also had a cardiac defect.

PMID- 7826001
TI  - A charmed life.
AB  - Boris Magasanik was born in Kharkoff, Ukraine, on December 19, 1919. He received
      his preliminary and secondary education in Vienna, Austria, and studied chemistry
      at the University of Vienna in 1937. He continued his studies at City College,
      New York (BS, 1941) and after one semester of graduate study at Pennsylvania
      State University, served in the US Army in England and France from 1942-1945. He
      obtained his PhD degree in biochemistry from Columbia University in 1948. A
      faculty member in the Department of Bacteriology and Immunology at Harvard
      Medical School from 1951 to 1960, he then continued his career as Professor of
      Microbiology at MIT where he served as head of the Department from 1967 to 1977.
      He became a member of the National Academy of Sciences USA in 1969 and received
      the Selman A Waksman Award in 1993. He is currently the Jacques Monod Professor
      Emeritus at MIT and is the author of over 240 publications dealing with microbial
      physiology and the regulation of gene expression in bacteria and yeast.

PMID- 7826002
TI  - Targeting proteins to the glycosomes of African trypanosomes.
AB  - Glycosomes are microbodies found in protozoa belonging to the order
      Kinetoplastida. These highly specialized organelles compartmentalize most of the
      glycolytic enzymes normally located in the cytosol of other eukaryotic cells. The
      recent success in expressing foreign proteins in Trypanosoma brucei has permitted
      a detailed analysis of glycosomal protein targeting signals in these organisms.
      These studies have revealed that the previously identified C-terminal tripeptide
      peroxisomal targeting signal also functions in the import of proteins into the
      glycosomes of T. brucei. However, the glycosomal and peroxisomal targeting
      signals differ in a few important ways. The C-terminal tripeptide sequence
      requirements for glycosomal protein targeting are comparatively relaxed. Of the
      three C-terminal amino acids, the first can be any small, neutral amino acid; the
      second should be capable of forming hydrogen bondings, whereas the third is a
      hydrophobic amino acid. This degenerate tripeptide sequence differs significantly
      from the more stringent requirements observed for the import of proteins into
      mammalian peroxisomes and thus represents an opportunity for designing peptide
      analogues that specifically block the glycosomal protein import for a possible
      antitrypanosomal chemotherapy. A recently described N-terminal signal that
      targets thiolase to the mammalian peroxisomes does not appear to function in
      import into the glycosomes. However, a novel internal targeting signal has
      tentatively been identified in at least one of the glycosomal proteins that can
      target a reporter protein to the glycosomes of T. brucei. Glycosome-deficient
      mutants have been isolated recently, which will aid in the identification of
      genes involved in the biogenesis of the glycosome.

PMID- 7826003
TI  - Human high density lipoprotein killing of African trypanosomes.
AB  - Trypanosoma brucei brucei is noninfectious to humans because of its sensitivity
      to the cytolytic activity of normal human serum. Biochemical evidence indicates
      that the active component of human serum is high-density lipoprotein (HDL).
      Several possible mechanisms have been proposed for the killing of trypanosomes by
      human HDL, and while a unified model that accounts for all experimental
      information is lacking, there is substantial evidence that receptor-mediated
      binding and endocytosis might be required for lysis. Trypanosomes resistant to
      the lytic effects of human HDL cause human sleeping sickness. The basis for the
      resistance of these parasites to HDL-mediated killing is unknown. The sensitivity
      of T. brucei brucei to the cytolytic action of human HDL is developmentally
      regulated and resistance correlates with life-cycle specific changes in
      macromolecular uptake by the organism.

PMID- 7826004
TI  - Genetics and biochemistry of dehalogenating enzymes.
AB  - Microorganisms that can utilize halogenated compounds as a growth substrate
      generally produce-enzymes whose function is carbon-halogen bond cleavage. Based
      on substrate range, reaction type and gene sequences, the dehalogenating enzymes
      can be classified in different groups, including hydrolytic dehalogenases,
      glutathione transferases, monooxygenases and hydratases. X-ray crystallographic
      and biochemical studies have provided detailed mechanistic insight into the
      action of haloalkane dehalogenase. The essential features are nucleophilic
      substitution of the halogen by a carboxylate group and the presence of a distinct
      halogen binding site, formed by tryptophan residues. This review summaries
      current knowledge on a variety of other dehalogenating enzymes and indicates the
      existence of a widespread and diverse microbial potential for dechlorination of
      natural and xenobiotic halogenated compounds.

PMID- 7826005
TI  - Comparative molecular biology of lambdoid phages.
AB  - Lambdoid phages are natural relatives of phage lambda. As a group, they are
      highly polymorphic in DNA sequence and biological specificity. Specificity
      differences have played a key role in identifying the specific sequences
      recognized by the N and Q antitermination proteins, the initiator O for DNA
      synthesis, the terminase system Nv1-A for cutting DNA during packaging, and the
      cI repressor protein. Variations that go beyond specificity differences are seen
      in packaging mechanism (headful in P22, specific cutting in lambdoid coliphages),
      in early control (terminator protein and phage-independent antitermination in
      HK022, phage-specific antitermination in lambda), in repression control
      (antirepressor operon in P22, absent in other lambdoid phages) and murein
      degrading enzymes (transglycosylase in lambda, lysozyme in other lambdoid
      phages). Sequence comparisons indicate that recombination among lambdoid phages
      is frequent in nature.

PMID- 7826006
TI  - Pathways and mechanisms in the biogenesis of novel deoxysugars by bacteria.
AB  - Science has long recognized the ubiquitously occurring deoxysugars as a novel and
      important class of carbohydrate, by virtue of the variety of potent and
      intriguing biological activities they exhibit. The study of the biosynthesis of
      these naturally vital molecules at a molecular level has received a great deal of
      attention in recent years, whether it be the well-established study of
      deoxyribonucleotide biosynthesis via ribonucleotide reductase or newer areas that
      include 3,6-dideoxyhexose construction and O antigen variation, as well as the
      emerging scrutiny of the biosynthesis of deoxysugar ligands of antibiotics and
      cardiac glycosides. This review attempts to update the various classes of deoxy,
      dideoxy, trideoxy, branched-chain, and amino sugars with respect to our current
      knowledge regarding the vast biological activities, genetics of formation, and
      molecular basis of their biosynthesis. In particular, the primary focus utilizes
      CDP-ascarylose biosynthesis, currently the best genetically and biochemically
      characterized dideoxysugar system, as a basis for comparison and postulation.
      This review helps display the elegant complexities of these essential natural
      saccharides and speculates upon tomorrow's potential applications.

PMID- 7826007
TI  - Genetic controls for the expression of surface antigens in African trypanosomes.
AB  - The major surface antigens of African trypanosomes, variant surface glycoprotein
      (VSG) and procyclin, are typical markers of their respective developmental
      stages, the bloodstream form and the insect-specific procyclic form. Although the
      role of procyclin is still unclear, variation of the VSG in the blood allows the
      parasite to escape the immune response of the host and develop a chronic
      infection. In this review, we discuss the available information concerning the
      genetic mechanisms that control the expression of VSG and procyclin during the
      life-cycle of the trypanosome. Unlike other eukaryotes, trypanosomes do not
      appear to primarily control the expression of their genes through a specific
      modulation of promoter activity. Antigenic variation in the bloodstream results
      either from DNA rearrangements or from a change in telomeric chromatin structure,
      and stage-specific regulation of antigen synthesis is linked to differential
      control of RNA elongation, processing, stability, and/or translation.
      Trypanosomes' apparent lack of transcription-initiation control probably relates
      to the general organization of genes in long polycistronic transcription units.
      Only two promoters for protein-encoding genes, those of VSG and procyclin, are
      known in trypanosomes, and these share properties with the ribosomal gene
      promoter.

PMID- 7826008
TI  - Living biosensors for the management and manipulation of microbial consortia.
AB  - The increasing interest in microbial ecology has resulted in the creation of new
      tools for the study of complex microbial interactions. Bioreporter genes are
      particularly useful because they provide a means of determining gene activity.
      Most bioreporter genes utilize a biochemical assay requiring destructive sampling
      of the microbial consortium, but lux bioreporter genes produce visible light when
      active. The measurement of light is rapid, sensitive, and quantifiable, and
      background signal is usually absent. The usefulness of lux bioreporters is shown
      in several examples that demonstrate the unique attributes of this bioreporter.
      Despite some limitations, bioluminescence has proved to be a useful bioreporter
      under both laboratory and field conditions. Technological developments are
      discussed that have the potential to increase the number of bioreporter genes.

PMID- 7826009
TI  - Iron and manganese in anaerobic respiration: environmental significance,
      physiology, and regulation.
AB  - Dissimilatory iron and/or manganese reduction is known to occur in several
      organisms, including anaerobic sulfur-reducing organisms such as Geobacter
      metallireducens or Desulfuromonas acetoxidans, and facultative aerobes such as
      Shewanella putrefaciens. These bacteria couple both carbon oxidation and growth
      to the reduction of these metals, and inhibitor and competition experiments
      suggest that Mn(IV) and Fe(III) are efficient electron acceptors similar to
      nitrate in redox abilities and capable of out-competing electron acceptors of
      lower potential, such as sulfate (sulfate reduction) or CO2 (methanogenesis).
      Field studies of iron and/or manganese reduction suggest that organisms with such
      metabolic abilities play important roles in coupling the oxidation of organic
      carbon to metal reduction under anaerobic conditions. Because both iron and
      manganese oxides are solids or colloids, they tend to settle downward in aquatic
      environments, providing a physical mechanism for the movement of oxidizing
      potential into anoxic zones. The resulting biogeochemical metal cycles have a
      strong impact on many other elements including carbon, sulfur, phosphorous, and
      trace metals.

PMID- 7826010
TI  - Mechanisms underlying expression of Tn10 encoded tetracycline resistance.
AB  - Tetracycline-resistance determinants encoding active efflux of the drug are
      widely distributed in gram-negative bacteria and unique with respect to genetic
      organization and regulation of expression. Each determinant consists of two genes
      called tetA and tetR, which are oriented with divergent polarity, and between
      them is a central regulatory region with overlapping promoters and operators. The
      amino acid sequences of the encoded proteins are 43-78% identical. The resistance
      protein TetA is a tetracycline/metal-proton antiporter located in the cytoplasmic
      membrane, while the regulatory protein TetR is a tetracycline inducible
      repressor. TetR binds via a helix-turn-helix motif to the two tet operators,
      resulting in repression of both genes. A detailed model of the repressor-operator
      complex has been proposed on the basis of biochemical and genetic data. The tet
      genes are differentially regulated so that repressor synthesis can occur before
      the resistance protein is expressed. This has been demonstrated for the Tn10
      encoded tet genes and may be a common property of all tet determinants, as
      suggested by the similar locations of operators with respect to promoters.
      Induction is mediated by a tetracycline-metal complex and requires only nanomolar
      concentrations of the drug. This is the most sensitive effector-inducible system
      of transcriptional regulation known to date. The crystal structure of the TetR
      tetracycline/metal complex shows the Tet repressor in the induced, non-DNA
      binding conformation. The structural interpretation of many noninducible TetR
      mutants has offered insight into the conformational changes associated with the
      switch between inducing and repressing structures of TetR. Tc is buried in the
      core of TetR, where it is held in place by multiple contacts to the protein.

PMID- 7826011
TI  - Biochemistry of the soluble methane monooxygenase.
AB  - The soluble form of methane monooxygenase (MMO) catalyzes the reaction NAD(P)H +
      O2 + CH4 + H+-->NAD(P)+ + H2O + CH3OH. Many other hydrocarbons serve as
      adventitious substrates. MMO consists of three protein components: component B,
      reductase, and hydroxylase (MMOH), the active site of which contains a hydroxo
      bridged dinuclear iron cluster that is the site of catalysis. Such a cluster has
      not been previously associated with oxygenases, and spectroscopic studies have
      been conducted to ascertain its structural features and accessibility. The
      mechanism of MMO has been investigated through the use of diagnostic chemical
      reactions and transient kinetics. Both approaches are consistent with a mechanism
      in which the diiron cluster is first reduced to the diferrous state and then
      reacts with O2. The O-O bond is apparently cleaved heterolytically to yield water
      and an [Fe(IV).Fe(IV)]=O species, which purportedly abstracts a hydrogen atom
      from methane to yield a substrate radical and a diiron cluster-bound hydroxyl
      radical. Recombination of the radicals yields the product methanol. An
      intermediate with the properties of the novel [Fe(IV).Fe(IV)] = O species has
      been trapped and characterized. This is the first such species to be isolated in
      biology. Meanwhile, the reductase and component B have roles in catalysis beyond
      simple electron transfer from NAD(P)H. These roles appear to be related to
      regulation of catalysis, and are mediated by the formation of specific component
      complexes that alter the physical and catalytic properties of MMOH at different
      stages of the turnover cycle.

PMID- 7826012
TI  - Rapid detection of food-borne pathogenic bacteria.
AB  - Recent advancements in biotechnology are rapidly altering the diagnostic
      procedures used in microbiologic analysis of foods. Biochemical identification
      tests have been miniaturized and automated, making them faster and more
      economical. Pathogenic bacteria that were previously isolated and identified
      after labor- and time-intensive enrichment and plating procedures can now be
      detected by measuring specific physicochemical changes resulting from their
      growth or metabolic activity. Nucleic acid and antibody-based assays are now used
      to rapidly and reliably detect pathogenic bacteria in foods. Nevertheless, foods
      offer unique challenges to the application of these techniques because of their
      complexity and variety, their interference with the rapid detection methods, and
      the need to detect pathogenic bacteria when they are present in foods at very low
      levels. Methods to sequester target pathogenic bacteria from interfering food
      components and to concentrate them in small volumes are needed to enable the
      efficient application of rapid detection and identification methods.

PMID- 7826013
TI  - Human papillomaviruses.
AB  - During the past 17 years 73 genotypes of human pathogenic papillomaviruses (HPV)
      have been identified. Most of them are found in benign proliferations; however,
      several have been discovered in malignant tumors. Specifically, cancer of the
      cervix, other anogenital cancers, but also some cancers of the skin, the oral and
      nasal cavity, and the rare periungual carcinomas have been linked to specific HPV
      infections. The pathogenesis of cancer of the cervix has been particularly well
      studied. Specific viral genes (E6 and E7) of high risk HPVs (types 16, 18, and
      others) act as oncogenes. Their expression emerges as necessary but not
      sufficient factors for malignant conversion. Besides stimulating cell
      proliferation, they are responsible for the genetic instability of the infected
      cells. Their transcriptional and functional activity is regulated by host cell
      genes. Mutational modifications of the latter appear to be required for malignant
      progression.

PMID- 7826014
TI  - The role of pH and temperature in the development of Leishmania parasites.
AB  - Protozoans of the genus Leishmania are obligate intracellular parasites that
      cycle between the midgut of sandflies and the phagolysosomes of mammalian
      macrophages and therefore are exposed to extreme environmental changes. Recent
      evidence obtained from in vitro experiments indicate that such environmental
      changes trigger a developmental program in the parasites. Thus, following heat
      shock, promastigotes from certain Leishmania species differentiate to
      amastigotes. Promastigotes also respond to acidification of their environment by
      changing the expression of a number of genes. However, the combination of both
      low pH and high temperature induces the transformation of the promastigote to the
      amastigote in all Leishmania species examined to date. This review discusses the
      role of pH and heat shock in gene regulation and its contribution to the
      differentiation processes in Leishmania spp. Cycling between cold-blooded insect
      vectors and the warm-blooded mammalian host is not unique to Leishmania spp., but
      typical to most parasitic protozoa. It is therefore likely that the mechanism of
      stress-induced differentiation is shared by other mammalian parasites.

PMID- 7826015
TI  - Antibiotics that inhibit fungal cell wall development.
AB  - The discovery of antifungal agents that possess selective toxicity against the
      eukaryotic fungal cell remains an important scientific challenge. The growing
      medical need for safe and effective antifungal agents stems from the rapidly
      increasing population of immunocompromised patients. Although the treatment of
      fungal infections is progressing steadily, currently available agents act on
      targets that are also found in mammalian cells. Ideally, a selectively toxic
      antifungal agent should be developed that interacts with a fungal target not
      found in other eukaryotic cells. This strategy involves selective inhibition of
      the biosynthesis of important structural elements in the fungal cell. The fungal
      cell wall is such a therapeutic target. In addition, antibiotics have been
      discovered that inhibit the development of the fungal cell. The major targets are
      glucan synthesis, inhibited by the echinocandin lipopeptides and the
      papulacandins; chitin synthesis, inhibited by the polyoxins and nikkomycins; and
      mannan, to which the pradimicins selectively bind. The extensively studied
      echinocandin lipopeptides are fungicidal agents with low toxicity, and one
      member, cilofungin--a semisynthetic analogue of echinocandin B--has been tested
      in the clinic. Newer echinocandins, such as LY303366 and the pneumocandins, have
      excellent activity against yeasts and Pneumocystis carinii infections in animals
      and show promise as potential clinical antifungal candidates. Chitin synthase
      inhibitors have been studied through chemical modification of the polyoxins and
      nikkomycins but are limited because of unfavorable pharmacokinetics. The
      pradimicins show the ability to bind mannan and thus exert an antifungal effect.
      The mode of action of this class of inhibitors is not fully understood, but their
      unique action may provide a better understanding of mannan as a target.

PMID- 7826016
TI  - Structural and functional properties of Trypanosoma trans-sialidase.
AB  - Sialic acids and sialidases play important roles in cellular interactions and
      modulate the recognition of pathogenic microbes by mammalian host cells.
      Protozoan parasites of the genus Trypanosoma express a unique sialic acid
      metabolizing enzyme. This enzyme, named trans-sialidase (TS), catalyzes the
      transfer of sialic acids from host glycoconjugates to acceptor molecules of the
      parasite plasma membrane. In African trypanosomes, the agents of sleeping
      sickness, TS is found only in forms developing within the insect vector, and the
      enzyme sialylates the major surface protein. In Trypanosoma cruzi, the causative
      agent of Chagas' disease in Central and South America, TS is expressed both in
      the insect and mammalian forms of the parasite. The T. cruzi enzyme has been
      biochemically characterized, and the gene encoding the enzyme has been cloned.
      The enzyme sialylates abundant mucin-like molecules present on the surface of the
      parasite. Several lines of evidence suggest that TS and sialic acid acceptors on
      the surface of T. cruzi participate in host-parasite interactions and mediate the
      initial stages of the trypanosomes' invasion of host cells.

PMID- 7826017
TI  - Designing microorganisms for the treatment of toxic wastes.
AB  - The genetic design of novel metabolic routes offers exciting possibilities for
      biological research and biotechnology, both in the exploration of the
      metabolic/evolutionary potential of cells and in the development of innovative
      applications. In this chapter, we review recent advances in the development of
      genetic tools and strategies for the design of new microorganisms for elimination
      of environmental pollutants. These include the design of regulated gene
      expression circuits that provide high levels of catalytic activity, even under
      environmental conditions that ordinarily repress expression of catabolic genes;
      the rational alteration of relevant properties of proteins that qualitatively or
      quantitatively restrict catabolic activities; the judicious assembly of gene
      blocks encoding selected metabolic modules to create novel metabolic routes and
      combinations of routes; and the design of microorganisms exhibiting properties
      that contribute to better process development.

PMID- 7826018
TI  - The role of the sigma factor sigma S (KatF) in bacterial global regulation.
AB  - The protein encoded by katF (also known as nur, appR, csi-2, abrD, and rpoS in
      various alleles) has been biochemically confirmed to be an alternate sigma
      transcription factor and renamed sigma S. Its synthesis is controlled
      transcriptionally and posttranscriptionally by as yet undefined mechanisms that
      are active well into stationary phase. sigma S controls a regulon of 30 or more
      genes expressed in response to starvation and during the transition to stationary
      phase. Proteins in the regulon, many of which have not been characterized,
      enhance long-term survival in nutrient-deficient medium and have a diverse group
      of functions including protection against DNA damage, the determination of
      morphological changes, the mediation of virulence, osmoprotection, and
      thermotolerance. Differential expression of subfamilies of genes within the
      regulon is effected by supplementary regulatory factors, working both
      individually and in combination to modulate activity of different sigma S
      dependent promoters.

PMID- 7826019
TI  - Strategies for the discovery of secondary metabolites from marine bacteria:
      ecological perspectives.
AB  - Marine microorganisms have become an important point of study in the search for
      novel microbial products. Today, both academic and industrial interest in marine
      microorganisms is on the rise, in part because of the growing number of unique,
      biologically active secondary metabolites reported from marine bacteria. Our
      ability to assess the biosynthetic potential of marine bacteria, however, is
      inevitably coupled to our basic understanding of their biology. This review
      summarizes the chemical discoveries and biological activities reported from
      marine bacteria and focuses upon several microbiological topics as they relate to
      natural product discovery, including the distributions, diversity, and
      culturability of marine bacteria, as well as the role of symbiotic bacteria in
      the production of substances previously ascribed to other sources.

PMID- 7826020
TI  - MSCRAMM-mediated adherence of microorganisms to host tissues.
AB  - Microbial adhesion to host tissue is the initial critical event in the
      pathogenesis of most infections and, as such, is an attractive target for the
      development of new antimicrobial therapeutics. Specific microbial components
      (adhesins) mediate adherence to host tissues by participating in amazingly
      sophisticated interactions with host molecules. This review focuses on a class of
      cell surface adhesins that specifically interact with extracellular matrix
      components and which we have designated MSCRAMMs (microbial surface components
      recognizing adhesive matrix molecules). MSCRAMMs recognizing fibronectin-,
      fibrinogen-, collagen-, and heparin-related polysaccharides are discussed in
      terms of structural organization, ligand-binding structures, importance in host
      tissue colonization and invasion, and role as virulence factors.

PMID- 7826021
TI  - Computational DNA sequence analysis.
AB  - This paper reviews several new developments in computer and statistical analysis
      of DNA and protein sequences. We present criteria and describe means for
      assessing and interpreting genomic inhomogeneities within and between sequences.
      These include: (a) characterizations of short oligonucleotide biases and general
      compositional tendencies; (b) molecular evolutionary reconstructions based on
      dinucleotide relative abundance distance measures and partial orderings; and (c)
      the application of r-scan statistics, quantile distributions, and score-based
      analyses to identify clustering, overdispersion, and excessive evenness in the
      distribution of a marker array along a sequence. These apply, for example, to
      restriction sites, microsatellite runs, regulatory motifs, and nucleosome
      placements. Furthermore, (d) the definition and determination of rare and
      frequent oligonucleotides and peptides provides another perspective on sequence
      heterogeneity, and (e) score methods are also applied in exon and gene locations.
      Most of the ideas and methods are illustrated with respect to bacteriophage
      genomes, to megabase amounts of several eukaryotic sequences, to a diverse
      collection of bacterial sets, to mitochondrial chromosomes, and to a broad
      assembly of viral genomes.

PMID- 7826022
TI  - Biology and genetics of prion diseases.
AB  - Enriching fractions from Syrian hamster (SHa) brain for scrapie prion infectivity
      led to the discovery of the prion protein (PrP). Prion diseases include scrapie
      of sheep, bovine spongiform encephalopathy (BSE) of cattle, as well as
      Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler-Scheinker disease (GSS),
      and fatal familial insomnia (FFI) of humans. Discovery of mutations in the PrP
      genes of humans with familial CJD, GSS, and FFI established that prion diseases
      are both genetic and infectious. Many lines of evidence have converged to argue
      that infectious prions are composed largely, if not entirely, of PrPSc molecules.
      Mice overexpressing mutant and wild-type transgenes develop neurologic illnesses
      spontaneously and produce prions as demonstrated by serial transmission of
      disease in rodents after inoculation of brain extracts. Although these and many
      other findings argue that prions are devoid of nucleic acid, the molecular basis
      of prion strains remains enigmatic. The formation of PrPSc from PrPC is a
      posttranslational process involving the conversion of alpha-helices into beta
      sheets. This conformational change in PrP appears to be the fundamental event
      that underlies prion propagation and the pathogenesis of prion diseases. The
      unique features of prion structure and propagation differentiate prions from all
      other transmissible pathogens.

PMID- 7826023
TI  - AIDS-associated mycoplasmas.
AB  - Previously, we hypothesized that mycoplasmas could act as cofactors accelerating
      the progression of HIV disease. In the present paper, we review the current
      knowledge on three mycoplasmas (Mycoplasma fermentans, M. penetrans, and M.
      pirum) that have been implicated as these putative cofactors. All three
      mycoplasmas have been isolated from patients with HIV infection, and serological
      studies have suggested that the presence of M. penetrans could be associated with
      HIV infection. These mycoplasmas share the capacity to hydrolyze arginine and
      ferment glucose as well as to attach to and invade eukaryotic cells. The possible
      mechanisms that could allow mycoplasmas to influence HIV pathogenesis,
      specifically through the activation of the immune system or the production of
      superantigen or by contributing to the oxidative stress observed in HIV-infected
      subjects, are discussed. These studies have offered and will continue to offer
      major contributions to a better understanding of mycoplasmal flora in humans and
      have begun to unveil some of the mechanisms of virulence of these organisms.

PMID- 7826024
TI  - Antisense RNA control in bacteria, phages, and plasmids.
AB  - Antisense RNA control is now recognized as an efficient and specific means of
      regulating gene expression at the posttranscriptional level. Almost all naturally
      occurring cases have been found in prokaryotes, often in their accessory genetic
      elements. Several antisense RNA systems are now well-understood, and these
      display a spectrum of mechanisms of action, binding pathways, and kinetics. This
      review summarizes antisense RNA control in prokaryotes, emphasizing the biology
      of the systems involved.

PMID- 7826025
TI  - Microbial iron transport.
AB  - Iron, an essential nutrient, is not readily available in aquatic or terrestrial
      environments or in animal hosts. Therefore, microbes have developed various
      strategies for acquiring iron while at the same time protecting themselves from
      iron's potential toxic effects. The major strategies used by bacteria and fungi
      to acquire iron include production and utilization of siderophores (ferric
      specific chelators); utilization of host iron compounds such as heme,
      transferrin, and lactoferrin; and reduction of Fe(III) to Fe(II) with subsequent
      transport of Fe(II). Selected examples are discussed with attention to which
      strategies work best in which environments. The similarities and differences
      among the different systems with respect to iron binding compounds, receptors,
      and regulation are also presented.

PMID- 7826026
TI  - Microbial biocatalysis in the generation of flavor and fragrance chemicals.
AB  - Microbial biocatalysis is used in the commercial production of many flavor and
      fragrance chemicals. Bulk flavoring chemicals such as citric acid, high fructose
      corn syrup, and glutamic acid are produced in millions of pounds annually using
      microbial processes. In the past few years, biocatalysis has also begun to play
      an increasingly important role in the production of many flavor and fragrance
      aroma chemicals. Microbial processes have traditionally played an integral role
      in the development of complex mixtures of flavor and aroma chemicals since the
      discovery of beer, wine, cheese, and soy sauce thousands of years ago. Today,
      contemporary microbiological techniques are being increasingly applied to enhance
      the efficiency of many microbial biocatalysts for the production of specific
      flavor and fragrance chemicals. However, to ensure commercial implementation of
      these new microbial processes, much more needs to be learned about the basic
      biochemistry and genetics of these novel biocatalysts.

PMID- 7826027
TI  - The extrachromosomal DNAs of apicomplexan parasites.
AB  - Molecular analyses in recent years have begun to elucidate the identity and role
      of two extrachromosomal DNAs found in apicomplexan parasites. One of these is a
      small tandemly repeated DNA that encodes three classical mitochondrial protein
      coding genes, attesting to its identity. This molecule also encodes mitochondrial
      rRNAs as small fragments in scattered locations. Despite their unusual nature,
      evidence suggests that these rRNAs are functional. They offer an opportunity to
      evaluate structure-function correlations in the absence of much of the more
      variable sequences found in other rRNAs. The second extrachromosomal DNA has
      characteristics reminiscent of chloroplast DNAs and thus points to an unexpected
      ancestry for the apicomplexans. Both DNAs are inherited maternally, as is usual
      for organelle DNAs, but their subcellular locations have not been demonstrated
      unequivocally. Although the majority of studies with these two DNAs thus far have
      been with Plasmodium species, evidence from other apicomplexans suggests that
      these unusual organelle genomes are common to the phylum.

PMID- 7826028
TI  - Advanced Technologies in Research, Diagnosis and Treatment of AIDS and in
      Oncology. Proceedings of an international workshop. Naples, October 21-22, 1993.

PMID- 7826029
TI  - Perspectives in research, diagnosis and treatment of AIDS and in oncology.

PMID- 7826030
TI  - Role of HIV as cofactor in HPV oncogenesis: in vitro evidences of virus
      interactions.

PMID- 7826031
TI  - Role of EBV and Ig/myc translocation in Burkitt lymphoma.

PMID- 7826032
TI  - Molecular pathogenesis of AIDS-related lymphomas.

PMID- 7826033
TI  - Detection and characterization of human T-lymphotropic viruses.

PMID- 7826034
TI  - Convergent infections: human papillomavirus and human immunodeficiency virus.

PMID- 7826035
TI  - Cofactors in the progression of HPV-associated tumors.

PMID- 7826036
TI  - Biological phenotypes of HIV-1 in pathogenesis and transmission.

PMID- 7826037
TI  - Human monoclonal antibodies for passive immunotherapy of HIV-1.

PMID- 7826038
TI  - Human monoclonal antibodies to HIV-1 define synergistic activities leading to
      enhanced neutralization.

PMID- 7826039
TI  - Polyvalent, recombinant HIV-1 virus-like particles: novel HIV-1 vaccine
      strategies.

PMID- 7826040
TI  - Pediatric HIV-1 infection: advances and perspectives in diagnosis and prognosis.

PMID- 7826041
TI  - Role of HIV-1 Tat in the pathogenesis of AIDS-associated Kaposi's sarcoma.

PMID- 7826042
TI  - Regulation of PDGF-B and PDGF receptor expression in the pathogenesis of Kaposi's
      sarcoma in AIDS.

PMID- 7826044
TI  - It's time for nurses to stop playing What's My Line? with the American public.

PMID- 7826043
TI  - In tribute to perioperative nurses.

PMID- 7826045
TI  - Celebrating 40 years of progress in perioperative nursing techniques.
AB  - Perioperative nurses have seen innumerable changes in their practices. During the
      past 40 years, new surgical and nursing techniques, new technology, and increased
      knowledge have resulted in improved care of the surgical patient. Much can be
      learned by reviewing the progress made by perioperative nurses during the past
      four decades.

PMID- 7826046
TI  - Strabismus repair in the pediatric patient.
AB  - Strabismus, one of the most common eye problems in children, is the inability to
      focus one or both eyes on an object. Strabismus results from poor extraocular
      muscle coordination. Patients with strabismus undergo surgery to reduce ocular
      deviation, restore normal vision, cosmetically straighten the eyes, and develop
      sensory fusion that will maintain motor alignment. Because strabismus is a
      muscular problem, patients with strabismus are at increased risk for malignant
      hyperthermia (MH). This risk is an important perioperative consideration. The
      perioperative nurse must be familiar with the MH protocol and be prepared to
      treat a child in this emergent situation.

PMID- 7826047
TI  - Right gastroepiploic artery conduit use in myocardial revascularization.
AB  - The majority of surgeons use the saphenous vein or internal mammary artery as
      conduits in coronary artery bypass grafting (CABG). Improved long-term patient
      survival rates after CABG have increased the need for alternative conduits in
      reoperations for myocardial revascularization. In the past 20 years, surgeons
      have begun using the right gastroepiploic artery (GEA) as an alternative conduit
      in CABG. Perioperative nursing care of patients undergoing right GEA grafting for
      myocardial revascularization includes documentation of patient problems and
      nursing actions taken; preoperative patient assessment and teaching;
      intraoperative management of patient positioning, temperature, and skin
      integrity; and postoperative care to maintain the patient's hemodynamic stability
      and avoid complications.

PMID- 7826048
TI  - Toward a standardized language to describe perioperative nursing.
AB  - The Nursing Interventions Classification (NIC) is a standardized language that
      identifies all interventions performed by nurses. Each nursing intervention has a
      label name, a conceptual definition, and a set of defining activities. The NIC
      provides a standardized nomenclature for automated databases, describes and
      measures nursing's contribution to health care, facilitates nursing education,
      supports clinical decision making, plans resource allocation, and facilitates
      nursing research. Perioperative nurses can use the NIC to describe and document
      their contributions to surgical patients' outcomes.

PMID- 7826049
TI  - Bacterial carriage on the fingernails of OR nurses.
AB  - This study provides statistically significant data that demonstrate that chipped
      fingernail polish or fingernail polish worn longer than four days fosters
      increased numbers of bacteria on the fingernails of OR nurses after surgical hand
      scrubs. There were no significant correlations between fingernail length and the
      numbers of bacterial colonies on the fingernails of the study groups tested after
      performing a standard surgical hand scrub. A convenience sample of 102
      perioperative nurses with either freshly polished fingernails; chipped fingernail
      polish; or natural, polish-free fingernails participated. The data suggest OR
      nurses can wear fresh fingernail polish on healthy fingernails without risking
      increased bacterial counts.

PMID- 7826050
TI  - Latex sensitivity among perioperative nurses.
AB  - To estimate the prevalence, risk factors, and clinical spectrum of adverse
      reactions to natural rubber latex-containing products among a national sample of
      perioperative nurses, the investigators administered a self-reporting
      questionnaire to a convenience sample of 2,200 members of the Association of
      Operating Room Nurses, Inc. Of the 1,738 nurses who responded, 369 (21%) reported
      latex reactions. Multivariate analysis identified a history of allergies to
      cosmetic powders, other allergies, chronic illnesses, and regular use of latex
      gloves as independent risk factors for reactions to latex-containing products.
      Localized reactions, such as contact dermatitis, were the reactions reported most
      commonly, although severe systemic reactions also were described.

PMID- 7826051
TI  - Perioperative nurses' roles in managing new technology.
AB  - The scientific knowledge base for medical technology doubles every two years.
      Whether new technologies will improve health care depends on how appropriately
      they are used; therefore, purchasing appropriate technology is crucial.
      Appropriate technologies include those that are valid, adaptable, acceptable, and
      affordable. Perioperative nurses can facilitate acquisition and use of
      appropriate technology in the OR by applying the process of technology assessment
      -a five-step process that examines the need, safety, effectiveness and efficacy,
      economic appraisal, and social impact of new technology. This article details the
      technology assessment process and provides methods of preparing perioperative
      staff members to use new technology.

PMID- 7826052
TI  - Proposed perioperative nurse translation of the federal clinical practice
      guidelines. Association of Operating Room Nurses.

PMID- 7826053
TI  - Social facilitation of eating among friends and strangers.
AB  - Research suggests that meals eaten with other people are larger than meals eaten
      alone. The effect of group size and acquaintance on consumption was investigated
      by serving dinner to female subjects alone, in pairs or in groups of four.
      Subjects dined alone, with friends or with strangers. Subjects in both pairs and
      groups of four ate more than did subjects alone, suggesting that the mere
      presence of others is more important in enhancing intake than the specific number
      of people present. Subjects with friends ate more dessert than subjects with
      strangers, indicating that the relationship of dining companions is an important
      factor contributing to social facilitation.

PMID- 7826054
TI  - Predictors and effects of long-term dieting on mental well-being and weight loss
      in obese women.
AB  - Sixty moderately obese women (mean BMI = 33, mean age = 43), randomized to a
      lactovegetarian or regular 1300-kcal weight-reducing diet were followed at 3, 8
      and 24 months. Weight follow-up was 92%, while 47% complied with the program
      throughout with no differences between the two diets with respect to compliance
      rate, weight loss or behavioral test results. Over 24 months compliers lost a
      mean 3.9 kg compared to a gain of 1.8 kg in the non-compliers. Short-term
      improvements in mental well-being measured by the Mood Adjective Check List
      deteriorated after 2 years to lower levels than at entry. Self-assessed
      motivation to diet was inversely related to mental well-being at two years.
      Positive long-term changes of functional status (Sickness Impact Profile) were
      found. Though subjective prediction of success measured after 3 weeks on diet
      predicted short-term and maximum weight loss, it did not predict ultimate
      outcome. More difficulties in resisting emotional and social eating cues (high
      disinhibition score on the Three-Factor Eating Questionnaire) before and during
      the diet predicted weight gain. The more initial health-related dysfunction (SIP)
      the greater the weight regain. Psychological characteristics at baseline did not
      predict compliance or overall weight loss. The magnitude of weight loss after 24
      months was related to amount and duration of maximum weight loss.

PMID- 7826056
TI  - Effect of effort on meal selection and meal acceptability in a student cafeteria.
AB  - Past laboratory and field studies show that the effort necessary to obtain food
      acts as a determinant of food selection and consumption. Two studies examined the
      impact of increasing the effort needed to obtain candy or potato chips on
      selection in a normal lunch setting. In the first study, food selection,
      acceptance and intake were obtained during the first week baseline and under the
      effort manipulation during the second week. With increased effort, candy
      selection dropped dramatically in week 2. Subjects substituted items from the
      desert, fruit and accessory food groups. In the second study, food selection and
      acceptance were measured during a 2-week baseline, a 3-week effort period, and a
      3-week recovery period. With increased effort, potato chip selection dropped
      dramatically and only partially recovered in the last phase. Subjects substituted
      items from the starch food group. These results demonstrate that changes in the
      effort needed to obtain food can have a nutritional impact in an actual eating
      situation and could be an important part of a healthy eating strategy.

PMID- 7826055
TI  - Cognitive control of eating behaviour and the disinhibition effect.
AB  - Restrained eaters have been reported to overeat following a high caloric preload,
      a phenomenon referred to as the disinhibition effect. However this effect has not
      been found when subjects were classified by the restraint subscales of the Three
      Factor Eating Questionnaire (TFEQ; Stunkard & Messick, 1985) or the Dutch Eating
      Behaviour Questionnaire (van Strien et al., 1986). The present study investigates
      the disinhibition effect in 133 normal-weight young women, using a two-factorial
      classification including the TFEQ-restraint and the TFEQ-disinhibition scale. The
      subjects were requested to consume ice-cream ad libitum during a taste test
      following a 200-ml milkshake preload or without preload. The results show that
      the behavioural disinhibition effect occurs only in subjects with simultaneous
      high scores on both subscales. In addition, subjects with high disinhibition
      scores consumed more ice-cream than low disinhibition subjects irrespective of
      their degree of restraint. While subjects with a more rigid control of eating
      behaviour did not show a difference in the amount of ice-cream consumed with or
      without preload, subjects with a more flexible control of eating behaviour
      reduced their intake following the preload condition. With regard to the Revised
      Restraint Scale (RRS Herman & Polivy, 1980) multiple regression results show that
      high RRS scores may be due to either higher TFEQ-restraint or higher TFEQ
      disinhibition scores. The interpretation of the results favours the renaming of
      the TFEQ-disinhibition scale to "susceptibility to eating problems" because high
      scores on this scale indicate overeating in a variety of situations without
      requiring prior inhibition i.e. dietary restraint. It is supposed that high
      susceptibility to eating problems may be caused by rigid control of eating
      behaviour, whereas flexible control of eating behaviour may be a less problematic
      strategy of long-term weight control.

PMID- 7826057
TI  - Accommodation of particular foods or beverages into spontaneously ingested
      evening meals.
AB  - Previous research has indicated that individual foods or beverages are ingested
      independently and do not produce adjustments to the intake of other constituents
      in the diet (de Castro, 1993; Wilson, 1991). In order to eliminate time of day as
      a potential contaminant, the present study investigated the accommodation of
      foods and beverages into the amount ingested at large evening meals only. Adults
      (n = 601) were paid to maintain detailed diaries of the timings, quantities and
      preparation techniques of everything they ingested for seven consecutive days.
      With the exceptions of soup, beef and chicken, 12 out of 15 types of drinks or
      foods were found to add to the total calories ingested in evening meals without
      displacing calories ingested in other forms, while ingestion of non-caloric diet
      sodas was not associated with differences in intake. The fat and protein, but not
      carbohydrate, contents of the items correlated with a measure of the satiating
      properties of the particular food or beverage, namely the correlation between the
      amount ingested of the particular type and the amounts of other nutrients
      ingested in the meal. The results confirm that intake at a meal is quite elastic
      and can be significantly influenced by the presence or absence of particular
      components of the meal and their constituents.

PMID- 7826058
TI  - Rats on a macronutrient self-selection diet eat most meals from a single food
      cup.
AB  - Computerized meal pattern analysis was performed on female Sprague-Dawley rats (n
      = 10). Rats were housed for 14 days in cages adapted for macronutrient selection.
      Rats selected their diet from vitamin and mineral supplemented, semipurified
      sources of carbohydrate, fat and protein, in three individual food cups. For
      analysis of meal patterns, minimum meal size was > 50 mg, and mean minimum
      intermeal interval was 7.9 min. Daily energy intake averaged 289.0 kJ, with 75%
      occurring during the dark cycle. Energy intake was 28% carbohydrate, 50% fat and
      22% protein. Of 12.3 daily meals, 56% were from one, 35% from two, and only 9% of
      the meals were from three food cups. Seventy percent of the time carbohydrate was
      the first meal of the dark cycle. The average number of meals per day eaten from
      carbohydrate, fat, and protein were not significantly different (6.9, 6.2 and
      5.6, respectively, p > 0.05). Energy intake for a meal was greatest when fat was
      eaten (18.35 kJ), than when either carbohydrate (8.68 kJ) or protein (8.97 kJ)
      was eaten. Meal duration was 7.03 min for carbohydrate, 3.75 min for fat, and
      7.47 min for protein. These results provide evidence that rats on a macronutrient
      self-selection diet eat most meals from a single macronutrient source.

PMID- 7826059
TI  - Meal pattern of rats during hyperphagia induced by longterm food restriction is
      affected by diet composition.
AB  - The influence of diet composition on feeding behavior during the hyperphagia
      induced by about 15% loss in body weight due to restricted feeding (5 g food/day
      for 7 days) was investigated in adult male rats. Rats were fed either a low-fat,
      high-carbohydrate diet (LF diet), a medium-fat diet (MF diet) or a carbohydrate
      free, high-fat diet (HF diet). The transient hyperphagia resulting from food
      restriction was greater in LF- and MF-rats than in HF-rats, in which a mild
      hypophagia was observed following the hyperphagia. Recovery of body weight was
      imperfect in the HF-rats in comparison to the unrestricted controls. During the
      hyperphagia, the meal pattern of LF- and MF-rats was mainly characterized by an
      increase in meal size, whereas HF-rats showed an increase in meal frequency.
      These observations indicate that control of food intake by body weight in LF- and
      MF-rats occurs mainly by modulation of the mechanisms producing meal-ending
      satiety, whereas in HF-rats the mechanisms eliciting meal initiation seem to be
      affected by body weight.

PMID- 7826060
TI  - Influences on food choice and intake. Commentary from the 1st and 2nd food choice
      conferences. Prediction of success at weight loss from behaviour, attitudes,
      emotional eating and self-efficacy.

PMID- 7826061
TI  - Does type of milk beverage affect lunchtime eating patterns and food choice by
      preschool children?

PMID- 7826062
TI  - [Recent trends in cancer in Japan and the world].
AB  - In Japan, the age-adjusted mortalities of cancer of the stomach, uterus, liver
      (females only) and esophagus (females only) have been declining in recent years,
      whereas those of cancer of the lung, large intestine, pancreas, bile ducts,
      prostate and ovary have been increasing. The pattern of cancer among Japanese
      seems to be approaching that in Western countries. Although cancer screening and
      improvements of diagnostic and therapeutic techniques may have contributed to the
      changes in cancer mortality, the main reasons for these changes may be due to
      changes in environmental factors such as tobacco and diet. The mortalities of
      cancer of the stomach, bile ducts and liver are relatively high in Japan compared
      to those of foreign countries, while those of cancer of the breast, uterus, lung
      and colon are relatively low.

PMID- 7826063
TI  - [Clinical evaluation of chemohormonal therapy as an initial treatment for stage
      D2 prostatic cancer--effect of UFT administration combined with hormonal
      therapy].
AB  - We evaluated the usefulness of hormonal therapy combined with UFT as initial
      treatment in comparison with hormonal therapy alone in 92 patients with Stage D2
      prostatic cancer treated at the Department of Urology, Dokkyo University School
      of Medicine between 1974 and 1993. Twenty-six of these patients were treated with
      diethylstilbestrol diphosphate (DESP) and castration (hormonal therapy alone
      group), and 23 patients were treated with UFT, DESP and castration (UFT combined
      therapy group). The 5-year survival rates calculated with Kaplan-Meier's method
      in the hormonal therapy alone group and the UFT combined therapy group were 34.6
      % and 38.3%, respectively. However, the 3-year survival rates of pathologically
      poorly differentiated adenocarcinoma in these groups were 30.0% and 50.0%,
      respectively. Based on these results, it was suggested that UFT administration
      combined with hormonal therapy is useful for pathologically poorly differentiated
      adenocarcinoma in Stage D2 prostatic cancer.

PMID- 7826064
TI  - [Method for daily administration of low-dose CDDP and 5-FU combined with
      radiotherapy for oral squamous cell carcinoma].
AB  - Daily administration of low-dose CDDP and 5-FU combined with radiotherapy was
      performed in three cases of oral squamous cell carcinoma in aged patients whose
      general condition was poor. One course of chemotherapy consisted of daily
      administration of CDDP (10 mg iv, days 1-5) and 5-FU (250-500 mg iv, days 1-5)
      with radiotherapy (total dose of 60-64 Gy). Two or three courses were performed
      at some interval. There were no severe side-effects except for mucositis. Tumors
      disappeared in all three cases, and a complete response was achieved in two
      cases. The method appeared to be safe and useful for oral squamous cell carcinoma
      patients of advanced age and poor general condition.

PMID- 7826065
TI  - [Two patients with far advanced gastric cancer responding to combination
      chemotherapy with 5-FU and CDDP].
AB  - Combination chemotherapy with 5-FU and CDDP was given to two patients with far
      advanced gastric cancer. One patient was associated with metastases of lung,
      liver, pancreas and Virchow and periaortic lymph nodes, and the other was
      associated with metastases of periaortic lymph nodes and malignant ascitis. The
      regimen consisted of 5-FU 1,000 mg/m2 (day 1-5, continuous infusion) and CDDP 100
      mg/m2 (day 3, 1 hr drip infusion). The interval was from the 6th to the 21st day.
      The response to chemotherapy showed shrinking of primary gastric lesions and
      metastases of liver, pancreas and periaortic lymph nodes, and disappearance of
      Virchow lymph nodes and malignant ascitis. Adverse reactions were
      thrombocytopenia (Grade 4), leukocytopenia (Grade 3), stomatitis (Grade 1, 3),
      vomiting (Grade 1, 2) and peripheral neuropathy (Grade 3). This therapy is
      thought to be effective against far advanced gastric cancer.

PMID- 7826066
TI  - [Case report of long-term survivor of advanced gastric cancer associated with
      peritoneal dissemination successfully treated with cancer chemotherapy].
AB  - We reported a case of gastric cancer with peritoneal dissemination, which was
      successfully treated by neoadjuvant chemotherapy and partial gastrectomy. A 71
      year-old female visited to our hospital because of umbilical tumor (Sister Mary
      Joseph's node). UGI series showed a Borrmann 1 type gastric cancer and
      laparoscopic examination revealed peritoneal metastasis. Her abdominal cavity was
      treated with MTX and CDDP and she was given intravenous administration of 5
      FU/LV. Repeated laparoscopy revealed complete disappearance of peritoneal
      seeding, and a partial gastrectomy was done. The histopathological findings of
      resected specimen showed the significant effects of preoperative chemotherapy.
      She has been living for more than 2 years with no recurrence after initial
      chemotherapy.

PMID- 7826067
TI  - [A case of remarkable response of colon cancer with multiple liver and bone
      metastasis treated with tegafur and cisplatin].
AB  - A 47-year-old man with ascending colon cancer with multiple liver metastases and
      bone metastasis (VII thoracic vertebra) showed a remarkable response to the
      combination therapy of tegafur and cisplatin. Tegafur (1,200 mg/day) was
      administered through continuous intravenous infusion mixed with IVH, and
      cisplatin was given every two weeks at a dose of 100 mg. The total dose of
      tegafur was 39.6g and that of cisplatin was 300mg. After therapy, primary and
      metastatic lesions were remarkably reduced according to various imaging
      techniques, and the serum CEA level of 34ng/ml at diagnosis decreased 3.7 ng/ml.
      Various tumor-related symptoms were improved. Drug toxicity caused slight nausea
      and leucopenia. Right hemicolectomy with R2 lymph node dissection was performed
      after chemotherapy. Histologically, primary lesion and regional lymph nodes
      showed diffuse fibrosis and necrosis, and only a few cancer cells remained some
      vessels. These results suggested that the combination chemotherapy of tegafur and
      cisplatin is useful for the treatment of colon cancer.

PMID- 7826068
TI  - [A case of pulmonary metastasis from colon cancer successfully treated with high
      dose 5'-DFUR].
AB  - We report a case, showing a complete response to high-dose 5'-DFUR, with
      pulmonary metastasis from colon cancer. A 52-year-old male patient underwent
      right hemicolectomy for ascending colon cancer in August, 1991. A recurrence of
      colon cancer developed in the left lower lung 16 months after surgery, and 5'
      DFUR was administered at a dose of 1,600 mg/body/day. The pulmonary metastatic
      lesion was undetectable on chest X-ray film 9 weeks after the start of this
      therapy. The dose of 5'-DFUR was then reduced to 600 mg/body/day. Although this
      condition was maintained for 22 weeks, chest X-ray film again showed the
      metastatic lesion at the same site in the lung as before. The pulmonary
      metastasis was resected completely in April, 1994. This is suggested to be an
      effective therapy for pulmonary metastasis from colon cancer.

PMID- 7826069
TI  - [Pharyngeal metastasis and arteriovenous fistula of renal cell carcinoma--report
      of a case].
AB  - A 76-year-old Japanese male consulted our hospital complaining of dysphagia. He
      also complained of dyspnea, and a cardiovascular disorder was detected.
      Otolaryngological examination revealed dysphagia due to pharyngeal tumor. Further
      examination detected left renal cell carcinoma with multiple pulmonary
      metastasis, and selective angiography revealed arteriovenous fistula in the
      primary tumor. After resection of the pharyngeal tumor and left nephrectomy,
      pharyngeal tumor was pathologically confirmed as metastasis of renal cell
      carcinoma. Furthermore, after left nephrectomy, the cardiovascular disorder
      gradually improved. Thus, the cardiovascular disorder was considered to have
      developed based upon the arteriovenous fistulae. Pharyngeal metastasis of renal
      cell carcinoma is extremely rare, and the cardiovascular disorder in this case
      was also an extrarenal manifestation.

PMID- 7826070
TI  - [Treatment of recurrent uterine endometrial cancer in adjuvant therapy with
      medroxyprogesterone acetate (MPA) in addition of etoposide].
AB  - In recent years, we treated recurrent uterine endometrial cancer by combined
      therapy including CDDP. But in poor cases, like renal failure and such, it is
      difficult to perform the therapy. Two cases of recurrent uterine endometrial
      cancer treated earlier with MPA were presently treated with an addition of
      etoposide. The first case was given etoposide (50 mg/m2/day 4 times for 21 days
      by oral administration). The target tumor mass was reduced in size, occult blood
      vanished, and the tumor marker was reduced. The other case was treated with
      etoposide, 50 mg/body/day for 21 days by oral administration, but because of
      diarrhea, the dose had to be decreased to 25 mg/body/day every day. The tumor
      marker was reduced and genital bleeding vanished. These cases suggested that
      etoposide-MPA combined therapy might be effective for recurrent uterine
      endometrial cancer of well-differentiated type.

PMID- 7826071
TI  - [Successful treatment of refractory anemia with excess of blasts in
      transformation with cytarabine ocfosfate].
AB  - A 58-year-old female was diagnosed as myelodysplastic syndrome (MDS) [refractory
      anemia with excess of blasts (RAEB)]. Although melphalan was administered, no
      response was obtained in the peripheral blood. Sixteen months after diagnosis,
      she developed RAEB in transformation (RAEB-t), and then overt leukemia. White
      blood cell (WBC) count elevated to 28,600/microliters with 34% of blasts. She was
      administered cytarabine ocfosfate (200 mg-->300 mg/day) orally, resulting in
      decrease of WBC count and blasts in peripheral blood. The drug has been given for
      11 months, and her hematological data have now remained stable in RAEB.
      Cytarabine ocfosfate might be a useful drug for the treatment of high risk MDS
      such as RAEB and RAEB-t.

PMID- 7826072
TI  - [Combination therapy of 5-FU and low dose CDDP for advanced and recurrence
      gastric cancer].

PMID- 7826073
TI  - [A case of neo-JP therapy in the treatment of ovarian carcinoma].

PMID- 7826074
TI  - [Blood pressure measurement under angiotensin II induced hypertension and a
      comparison of Riva-Rocci-Korotkoff method with automatic devices].

PMID- 7826075
TI  - [Neuroblastoma].
AB  - Neuroblastoma is the most common and highly malignant tumor. The 2-year survival
      rate for NB patients for 1970s was 32% in US and 29% in Japan. But, improvement
      of prognosis was observed by recent advances in surgery, chemotherapy and
      numerous other supportive therapies. We introduce the some treatment regimens to
      patients with neuroblastoma which should be selected by the age and the stage at
      diagnosis and other prognostic factors such as N-myc amplification, trk
      overexpression, chromosome anomalies (lp-. double minutes, homogeneous staining
      region) of neuroblastoma cells and histological pathology. As a general rules,
      patients under 1 year of age without unfavorable prognostic factors should be
      treated less intensive regimen, even their tumors are progressive stages.
      Conversely, patients with progressive stages over 1 year of age without
      unfavorable factors, it is necessary to treat with intensive protocol.
      Furthermore, to patients of all age group with unfavorable factors, they are
      given a very strong intensive treatment through advances in supportive therapies
      such as the new antiemetics, G-CSF, antibiotics, or IVH etc.. Recent treatment
      regimens to the patients with neuroblastoma are presented.

PMID- 7826076
TI  - [Therapeutic strategy for advanced non-small cell lung cancer].
AB  - This paper describes the recent progress in the treatment of advanced non-small
      cell lung cancer (NS CLC) as follows: 1) The results of single agent chemotherapy
      in NSCLC, particularly development of new drugs, are summarized. CPT-11, taxol,
      taxotere, vinorelbine and gemcitabine have appeared to have a response rate of
      more than 20%. In addition results of phase I and II trials that involved these
      agents as part of combination regimens are presented. 2) We summarize 8
      randomized trials of combination chemotherapy compared with best supportive care.
      These studies have provided that combination chemotherapy modestly improves
      survival of patients with advanced NSCLC. 3) Although several randomized trials
      with adjuvant or neoadjuvant chemotherapy have reported in the patients with
      locally advanced NSCLC, we have still not confirmative results. 4) Cisplatin
      based combination chemotherapy followed by chest irradiation improves outcomes of
      the patients with stage IIIA or IIIB unresectable NSCLC as compared with
      chemotherapy alone or radiation therapy alone. In spite of these advances further
      investigations are necessary to improve the treatment results of patients with
      advanced NSCLC.

PMID- 7826077
TI  - [Strategy for the treatment of hepatocellular carcinoma].
AB  - Hepatocellular carcinoma is a refractory cancer for the following two reasons:
      the tumor characteristics, including formation of tumor thrombus in the portal
      vein, metastasis within the liver and multicentricity of growth; and liver
      function disturbance due to cirrhotic change by B- or C-type viral infection. The
      most desirable treatment is hepatic resection, the only method producing a
      disease-free condition. However, there are not many cases that meet the
      indications for hepatic resection, since they have advanced lesions and/or liver
      dysfunction. If one cannot perform a hepatic resection, other suitable therapies
      should be selected, including transcatheter arterial embolization, percutaneous
      ethanol injection therapy, ligation of hepatic artery, irradiation, chemotherapy
      from hepatic artery via reservoir and so on. Combined therapy may sometimes be
      necessary for satisfactory efficacy. For long-term survival it is very important
      to do a close follow-up study over a long period. This encourages us to detect
      new lesions earlier and then perform suitable therapy again. Notifying patients
      of the disease and obtaining informed consent are needed for this long-term
      follow-up and treatment. When patients were examined who had first undergone
      hepatic resection and then hepatic re-resection for recurrence, we found that
      their survival rate was not different from that in the non-recurrent cases. This
      result indicates that overcoming refractory  hepatocellular carcinoma requires a
      multidisciplinary treatment in which hepatic resection is the main means.

PMID- 7826078
TI  - [Clinical and histological effect of induction chemotherapy with peplomycin,
      vincristine, mitomycin C and cis-platinum on oral squamous cell carcinomas].
AB  - Twenty one patients with resectable oral cancer received two courses of induction
      chemotherapy with peplomycin (PEP), vincristine (VCR), mitomycin C (MMC) and
      cisplatin (CDDP). Five patients had a complete response to the therapy and 9 had
      a partial response. Histological evaluation by Ohboshi-Shimozato classification
      indicated that Grade IV was obtained in 7 cases, Grade III was in 4 cases.
      Moreover, the study suggested that this regimen was less effective for metastatic
      lymph lesions than that for the primary tumors.

PMID- 7826079
TI  - [Late phase II trial of RP56976 (Docetaxel) in patients with non-small-cell lung
      cancer].
AB  - A late phase II trial on RP 56976 (Docetaxel) was carried out against stage IIIB
      or IV non-resectable non-small cell lung cancer as a multicenter cooperative
      trial. Of 78 enrolled patients, seventy five patients were eligible and 71 were
      evaluable for the response. The overall response rate was 19.7% (14/71): 27.9%
      (12/48) of patients with adenocarcinoma and 10.0% (2/20) of patients with
      squamous cell carcinoma responded to docetaxel. The response rate was 15.0%
      (3/20) in patients with stage III B disease and 21.6% (11/51) in patients with
      stage IV disease. Leukopenia (neutropenia) occurred frequently, but most tended
      to recover in a short period of time. Other adverse reactions included
      nausea/vomiting, anorexia, general malaise, alopecia, all of which were not
      severe. Severe hypersensitivity reactions occurred in 2 patients (2.7%). The
      results seemed to show usefulness of docetaxel for the treatment of patients with
      non-small cell lung cancer.

PMID- 7826080
TI  - [A late phase-II trial comparing KW-2307 with vindesine in non-small cell lung
      cancer (1). Lung cancer section in KW-2307 Study Group].
AB  - A multicenter cooperative study was performed to compare KW-2307 (KW), a novel
      vinca alkaloid (VA) derivative, and vindesine (VDS), with respect to tumor
      response and toxicity in patients (pts) with non-small cell lung cancer. In the
      former part of the trial, pts received monotherapy with KW 25 mg/m2 or VDS 3
      mg/m2. Pts refractory to treatment with KW or VDS were crossed over to treatment
      with VDS (3 mg/m2/W x 3) or KW (20 mg/m2/W x 3), respectively, in combination
      with cisplatin (CDDP) 80 mg/m2. Both drugs were administered in 4 courses or more
      once weekly by intravenous bolus injection in monotherapy. In the subsequent
      combination therapy, non-responders were treated with CDDP on day 1 and KW or VDS
      on day 1, 8 and 15 with a course of 28 days, and treatment was given in 2 courses
      or more in principle. According to the method of O'Brien/Fleming, comparison of
      tumor response between the 2 treatment groups in the 2nd stage was performed in
      154 cases. The response rate of KW group (29.4%, 22/75) was significantly better
      than that of VDS group (9.3%, 7/75). The main adverse effect in both groups was
      leukopenia (neutropenia), and no significant difference was observed between the
      incidence in each group. Among other adverse effects, increased GOT, fever and
      phlebitis were slightly more often found in KW group, and alopecia and
      paresthesia a little more in the VDS group. In the later part of combination
      therapy with CD DP, the KW group achieved PR in 10 of 34 pts (29.4%), and no
      response was observed in the VDS group (28 pts).

PMID- 7826081
TI  - [Evaluation of new style of drug delivery system for primary lung cancer:
      intermittent intra-arterial injection therapy with subcutaneous infusible port I.
      -Temporary changes in feeding arteries of lung cancer in processes of intra
      arterial injection therapy].
AB  - Arterial injection therapy for lung cancers is concentrated on the bronchial
      arteries, because they are reported by the main feeders of lung cancers. In the
      present study, we attempted intermittent arterial injection therapy with
      implantable port system. In the cases of lung cancers, in the present study,
      tumors were mainly fed by bronchial arteries originating from intercostal
      bronchial arteries in right lungs, and those directly originating from aorta in
      the left lungs. However, in the processes of BAI (Bronchial Arterial Injection
      Therapy), main feeders often were obstructed and the new feeders originated from
      branches of subclavian arteries, such as thyro-cervical truncks, internal mammary
      arteries, thoraco-acromial arteries and intercostal arteries. They formed
      networks surrounding the lungs. Adequate study of the feeding arteries should be
      performed in the course of arterial injection therapy of lung cancers.

PMID- 7826082
TI  - [Efficacy of combination chemotherapy with mitoxantrone, vincristine,
      prednisolone (MVP) for recurrence of breast cancer].
AB  - Fourteen patients with recurrent breast cancer were treated with a combination of
      mitoxantrone (10 mg/m2 iv, day 1), vincristine (1 mg/m2 iv, day 1) and
      prednisolone (30 mg/day day 1-7). Cycles were repeated every 4 weeks and all
      patients received more than 3 cycles. The objective response rate was 70.0% (7 of
      10). In two patients, the treatment has been continued now for more than one
      year. In these 2 patients, the duration of response is more than 40 weeks. The
      toxicity was primarily myelosuppression. Five of 14 patients (35.7%) had
      leukopenia of Grade 3 and 4. These patients received G-CSF therapy and recovered
      well from leukopenia. Nausea and vomiting were well tolerated, probably by
      prednisolone. This regimen was especially superior in the maintenance of quality
      of life because hair loss was much less compared to CAF (cyclophosphamide, ADM, 5
      fluorouracil) treatment. In conclusion, MVP treatment is highly effective and
      safe for the treatment of recurrent breast cancer.

PMID- 7826083
TI  - [Effect of continuous infusion of 5-fluorouracil and daily low-dose cisplatin for
      inoperable recurrent cancer of the stomach and colon].
AB  - With the use of cisplatin to enhance the effect of 5-FU, a combined approach was
      designed to treat patients with inoperable recurrent cancer of the stomach (15)
      and colon (6). This CDDP-5-FU therapy consisted of intermittent infusion of CDDP
      at a dose of 6 mg/m2 every day and continuous infusion of 5-FU at a daily dose of
      200 mg/m2 for 2 weeks with a 2-week interval in between. There were 1CR and 6PR,
      and the overall response rate was 40.0%. Toxicity was manifested in slight nausea
      or vomiting in two patients (10.0%), but there was no nephrotoxity.
      Thrombocytopenia of Grade 4 was found in 1 patient and leucopenia of Grade 3 in
      another. The efficiency of performance status was in 14 patients (66.7%).
      Combination of daily low-dose cisplatin and 5-FU is a tolerable treatment for
      patients with inoperable recurrent stomach and colon cancer. It is suggested that
      CDDP plays a role as not only an effector but also a modulator in biochemical
      modulation of 5-FU in this therapy. The infusion schedule is also suitable for
      chemotherapy of outpatients. Further studies on the appropriate infusion of CDDP
      and 5-FU are needed.

PMID- 7826084
TI  - [Current and future approaches to therapy for multiple myeloma].
AB  - Multiple myeloma accounts for approximately 10% of hematologic cancers; it is
      characterized by an uncontrolled malignant growth of plasma cells occurring
      usually in the bone marrow or sometimes in other body sites as well. Malignant
      myeloma cells produce monoclonal immunoglobulins appearing as monoclonal spikes
      in the serum and/or urine. Patients with multiple myeloma suffer from various
      clinical features including bone destruction, bone marrow suppression, impaired
      renal function, hypercalcemia, serious infection, and amyloidosis. The
      combination of melphalan and prednisolone has been used as a standard therapy for
      this disease for over 30 years. The median survival of patients with multiple
      myeloma is 2.5-3 years, and only 10% of them survive longer than 10 years. To
      improve the prognosis for multiple myeloma, some strategies have been attempted.
      In this article, we introduce combination chemotherapy, interferon therapy, and
      bone marrow transplantation as newer approaches to therapy for multiple myeloma
      based on the biological characteristics of intractable multiple myeloma. Future
      therapeutic approaches are also discussed.

PMID- 7826085
TI  - [Effect of chemotherapy using irinotecan (CPT-11) against recurrent colorectal
      cancer].
AB  - Irinotecan (CPT-11) is a camptothecine derivative with antitumor activity and
      inhibitor of DNA topoisomerase I. CPT-11 showed a excellent and broad anticancer
      activity against several malignant tumors. In this study, as in the Japanese
      phase II study, CPT-11 was administered at 100 mg/m2 weekly by intravenous
      infusion against 10 patients with recurrent colorectal cancer. Median total dose
      was 513 mg. Partial responses were obtained in 4/10 patient (40%). Lung
      metastases showed a 33.3% response and lymphnode metastases showed a 60%
      response. However, liver metastases showed no response. The median duration to
      the onset of partial response was 20 days and the median overall response
      duration was 89 days. Adverse effects were leukopenia (40%), nausea, vomiting and
      diarrhea (80%), fever (20%), and general malaise (30%). These were generally well
      tolerated and reversible. From these results, CPT-11 seemed to become an
      effective drug for recurrent colorectal cancer. Further trials of combination
      chemotherapy utilizing CPT-11 seem to be warranted.

PMID- 7826086
TI  - [Effect of intravaginal administration of cisplatin (CDDP) suppositories to
      uterine cervical cancer--blood and tissue concentrations and the therapeutic
      effects].
AB  - Four patients with cervical cancer (squamous cell carcinoma: two cases of stage
      Ib, one of stage IIa, adenocarcinoma: one of stage Ib), were treated
      preoperatively by intravaginal administration of CDDP (20 mg) suppositories with
      pessary 7 times every other day. The uptake, distribution and antitumor effect of
      CDDP were investigated. Results were as follows. 1) Serum total platinum (Pt)
      concentration varied between individual patients. Cmax profile (0.17-0.57
      micrograms/ml) of Pt was observed at 12 hours after the total dose of 140 mg
      administration in all patients. 2) The tissue Pt concentration showed high values
      in the cervix (average 55.4 micrograms/g), followed by the vagina (13.13),
      endometrium (3.17), uterine wall (0.64), ovary (0.57), lymph node group:
      parametrial (1.14), obturator (0.34), inguinal (0.28), external iliac (0.51),
      internal iliac (0.42) and common iliac (0.54). Para-aortic node value was too low
      to detect. 3) Colposcopic findings were disappearance of bleeding and reduction
      of tumor outgrowth. Microscopic findings were degeneration and necrosis of cancer
      nest from the surface to about 2 mm depth of the cervix. In conclusion, it may be
      necessary to improve CDDP penetration from the tumor surface for effective local
      chemotherapy.

PMID- 7826087
TI  - Human immunodeficiency virus and the Gianotti-Crosti syndrome.

PMID- 7826088
TI  - Confluent and reticulated papillomatosis of Gougerot and Carteaud: minocycline
      deserves trial before etretinate.

PMID- 7826089
TI  - Acquired localized cutis laxa due to cutaneous lymphoplasmacytoid lymphoma.

PMID- 7826090
TI  - Conjugal porphyria cutanea tarda.

PMID- 7826091
TI  - Confusion after topical use of resorcinol.

PMID- 7826092
TI  - The treatment of acyclovir-resistant herpes zoster with trifluorothymidine and
      interferon alfa.

PMID- 7826093
TI  - Studies in patients with corticosteroid contact allergy. Understanding cross
      reactivity among different steroids.
AB  - BACKGROUND AND DESIGN: Most corticosteroid-allergic patients react to several
      corticosteroids. Irrefutable proof for the existence of cross-reactions is
      provided by reactions to substances to which the patient has never been exposed.
      Four groups of cross-reactions have been proposed, and our own observations
      support this. However, we have found that budesonide, in particular, tends to be
      involved not only in cross-reactions with corticosteroids of its own group (group
      B) but also with those of the ester group (group D). To test clinical
      observations on patients sensitive to corticosteroids and to establish a
      molecular basis for cross-reactivity patterns, a statistical analysis of our
      cases and a conformational study of major corticosteroids were performed.
      RESULTS: Statistically highly significant positive or negative correlations were
      found for the combination of tixocortol pivalate plus hydrocortisone and
      hydrocortisone plus budesonide, respectively. This indicates that budesonide and
      hydrocortisone or tixocortol pivalate detect different groups of corticosteroid
      sensitive patients. Moreover, significant positive correlations were found
      between budesonide and amcinonide, both molecules belonging to the acetonide
      group C, and also between budesonide and some esters of group D such as
      hydrocortisone-17 butyrate and alclometasone dipropionate. These clinical
      observations were fully supported by a conformational analysis of the electronic
      shape of corticosteroids involved in this study. Groups A, B, and D were found to
      be highly homogeneous within each group in terms of molecular structures, while
      significant differences were observed among the groups. The special behavior of
      budesonide can be fully explained on the base of its unique molecular structure.
      Finally, molecular characteristics have been defined for each group. This could
      be useful for the prediction of potential cross-reactions to new corticosteroid
      molecules. CONCLUSIONS: The statistical analysis confirms that tixocortol
      pivalate and hydrocortisone contact allergies are definitely associated, while
      reactions to budesonide are strongly correlated with the reactions to both the
      acetonide group and the ester group. These clinical observations are fully
      supported by the conformational analysis of the molecules involved in this study.
      Tixocortol pivalate and budesonide should certainly be added to the standard
      series for the detection of patients sensitized to corticosteroids.

PMID- 7826094
TI  - Possible role of cytokines in cellular proliferation of the skin transplanted
      onto nude mice.
AB  - BACKGROUND AND DESIGN: In recent studies on the behavior of aged skin
      transplanted onto nude mice, the epidermis of aged and young skin showed an
      increase in proliferation and thickness following engraftment, and became almost
      identical. The aim of this study was to ascertain a possible role for the release
      of local cytokines in this phenomenon. Grafted human skin was injected
      intradermally with anti-interleukin-6 (IL) and anti-IL-1 alpha, and comparisons
      of epidermal thymidine incorporation and thickness were made. Grafts injected
      with irrelevant antibodies served as control. RESULTS: Interleukin-6 and IL-1
      alpha expression were studied in grafts by immunoperoxidase staining. Only IL-6
      expression was found in the 1-month grafts. Intradermal injections of anti-IL-1
      alpha and anti-IL-6 showed an inhibitory effect on cellular proliferation in the
      epidermis. A significant difference in the response of epidermal proliferation
      and, consequently, in thickness was found in samples injected with anti-IL-1
      alpha and anti-IL-6 compared with those injected with irrelevant antibodies.
      CONCLUSIONS: These data may indicate that local cytokines released by the
      keratinocytes are involved in the cellular proliferative activity in skin
      engrafted onto the mice.

PMID- 7826095
TI  - IgM autoantibodies to 180- and 230- to 240-kd human epidermal proteins in
      pregnancy.
AB  - BACKGROUND AND DESIGN: A previous study has suggested that there is a novel
      entity among the polymorphous eruptions of pregnancy (PEP) associated with
      circulating anti-basement membrane zone IgM autoantibodies. To determine if the
      presence of anti-basement membrane zone IgM autoantibodies is a feature of PEP,
      serum samples from 52 patients with a PEP, 69 healthy pregnant women, and 42
      nonpregnant women were prospectively evaluated by indirect immunofluorescence
      using salt-split human skin as substrate. Serum samples were also tested by
      immunoblotting using keratinocyte extracts and anti-human IgM antibodies. The
      reactivity of some serum samples was examined using two recombinant bullous
      pemphigoid antigen proteins. RESULTS: The percentage of women with a PEP, healthy
      pregnant women, and nonpregnant women who had anti-basement membrane zone IgM
      antibodies by indirect immunofluorescence was similar: 12%, 10%, and 14% of
      cases, respectively. By immunoblotting, 14% of the serum samples from the
      patients with a PEP, 12% of the serum samples from the healthy pregnant women,
      but only 2% of the serum samples from the nonpregnant women contained IgM
      antibodies that reacted with epidermal proteins of 180 and/or 230 to 240 kd. The
      recombinant bullous pemphigoid antigen proteins were not recognized by any of the
      serum samples that showed a reactivity by immunoblotting using keratinocyte
      extracts. CONCLUSION: There is no evidence for the existence of a novel entity of
      pregnancy defined by circulating anti-basement membrane zone IgM autoantibodies.
      Immunoblotting detects IgM autoantibodies that react with epidermal proteins of
      180 and/or 230 to 240 kd. These autoantibodies appear to be more frequent in
      pregnant than in nonpregnant women. Although the nature of the target antigen(s)
      remains to be established, pregnancy may be associated with low levels of IgM
      autoreactivity against epidermal proteins.

PMID- 7826096
TI  - Incidence and distribution of subepidermal autoimmune bullous skin diseases in
      three French regions. Bullous Diseases French Study Group.
AB  - BACKGROUND AND DESIGN: The incidence and distribution of autoimmune subepidermal
      bullous diseases were estimated from prospective data (including immunoelectron
      microscopy) obtained from 100 cases during a mean period of 35 months in three
      university dermatologic centers in Amiens, Limoges, and Tours, France, that
      correspond to a cumulative reference population of 3.55 x 10(6). RESULTS: Using
      data from these regions, we found a mean annual incidence of autoimmune
      subepidermal bullous diseases to be 10.4 per million people and, therefore,
      estimated the overall number of new cases of these disorders in France to be
      about 590 cases per year. According to clinical and immunoelectron microscopic
      criteria, a precise diagnosis was established in 94 cases, distributed as
      follows: bullous pemphigoid, 69 cases; cicatricial pemphigoid, 12 cases; linear
      IgA dermatosis, five cases; herpes gestationis, four cases; epidermolysis bullosa
      acquisita, two cases; and vesiculobullous systemic lupus erythematosus, two
      cases. CONCLUSION: Our prospective study is the first assessing the incidence and
      distribution of autoimmune subepidermal bullous disorders that systematically
      included immunoelectron microscopic data. Our estimated incidence of bullous
      pemphigoid (seven new cases per million people per year) is large enough to
      establish bullous pemphigoid as the major autoimmune subepidermal bullous disease
      for the purpose of therapeutic trials. On the contrary, all other disorders,
      particularly epidermolysis bullosa acquisita (estimated annual incidence, 0.17 to
      0.26 per million people), were very rare and reflect the paucity of patients
      available for short-term clinical studies in France.

PMID- 7826097
TI  - Silicone breast implant-associated scarring dystrophy of the arm.
AB  - BACKGROUND: Breast implants have been known to rupture after trauma or closed
      capsulotomy with spread of the gel down the arm or abdominal wall. Nodular
      foreign-body granulomatous reactions have been reported in these cases. We report
      the unique occurrence of significant overlying scarring and ulceration following
      silicone gel migration down the affected arm. OBSERVATIONS: A 47-year-old woman
      experienced rupture of her right silicone gel implant with migration of the
      silicone down her arm 10 years before our examination. Skin changes with atrophic
      hidebound scarring and ulceration slowly progressed over the last 7 years.
      Radiographs and magnetic resonance imaging scans demonstrated material consistent
      with silicone in the soft tissues. CONCLUSIONS: Silicone is not an inert
      substance and can rarely result in devastating local tissue destruction where
      migration has occurred. The possibility of significant silicone gel migration
      should be considered during evaluation of patients with ruptured implants.

PMID- 7826098
TI  - Angiokeratoma corporis diffusum and arteriovenous fistulas with dominant
      transmission in the absence of metabolic disorders.
AB  - BACKGROUND: A three-generation family with members affected by angiokeratoma
      corporis diffusum (ACD) and arteriovenous fistulas of the legs is described. Our
      purpose was to investigate possible lysosomal storage defects previously
      described in association with ACD. OBJECTIVE: Results of physical examination of
      both affected and unaffected family members were otherwise normal as was the life
      span. The inheritance pattern of both ACD and arteriovenous fistula traits was
      autosomal dominant, with variable expressivity and incomplete penetrance.
      Microscopic examination of ACD lesions showed dilated capillaries without
      vacuolation of cells. Ultrastructural studies failed to reveal lysosomal
      abnormalities. Normal levels of alpha-galactosidase, beta-galactosidase, alpha
      fucosidase, and alpha-sialidase were detected in peripheral blood leukocytes and
      skin fibroblasts. CONCLUSIONS: The association of autosomal dominant ACD and
      arteriovenous fistulas might represent a novel syndrome. However, pathogenesis of
      these lesions remains unknown.

PMID- 7826099
TI  - Calciphylaxis in three patients with end-stage renal disease.
AB  - BACKGROUND: Calciphylaxis is a rare and life-threatening condition of progressive
      cutaneous necrosis secondary to small- and medium-sized vessel calcification seen
      almost exclusively in patients with end-stage renal disease and
      hyperparathyroidism. Two patients had bullous lesions preceding their ulcerative
      lesions, an unusual presentation of this entity. One patient also had penile
      involvement that, to our knowledge, has not been described previously.
      OBSERVATIONS: Three patients, all of whom were being maintained on hemodialysis,
      developed painful, progressive leg ulcerations. Two patients had elevated
      parathormone levels, and the third patient did not. All patients had only very
      modest increases in their calcium x phosphate product. CONCLUSIONS: Calciphylaxis
      should be included in the differential diagnosis of panniculitis and vasculitis.
      It is important to diagnose promptly, as early treatment may prevent progression.

PMID- 7826100
TI  - Streptococcal toxic shock-like syndrome.
AB  - BACKGROUND: After decades marked by a decrease in the incidence and severity of
      scarlet fever and streptococcal soft-tissue infections, invasive infections with
      group A streptococci have reemerged as a global public health problem. Sporadic
      outbreaks of a rapidly progressive disorder characterized by fever, shock,
      desquamating rash, and multiorgan system failure often associated with severe
      suppurative soft-tissue infection have recently been recognized in young,
      otherwise-healthy adults. Referred to as streptococcal toxic shock-like syndrome,
      this acute, progressive, often fatal illness appears to be related to an overall
      change in the virulence of group A streptococci and the reappearance of highly
      mucoid exotoxin-producing strains. However, the relationship between virulence
      factors, epidemiological features, and precise pathogenesis of these infections
      remains unclear. OBSERVATIONS: The 80% incidence of soft-tissue involvement in
      streptococcal toxic shock-like syndrome and the high frequency of progression to
      necrotizing fasciitis, myositis, or even death are unprecedented. The type and
      extent of tissue injury, systemic toxicity, and multiorgan system failure
      associated with this syndrome appear to be mediated by streptococcal pyrogenic
      exotoxins via the induction of biologically potent endogenous cytokines. The
      observed increase in the incidence and severity of invasive group A streptococcal
      infections coincides with the resurgence of genetically related, highly virulent
      strains of Staphylococcus pyogenes that express an invasive phenotype and carry a
      specific gene for pyrogenic exotoxin A. CONCLUSIONS: The changing spectrum of
      invasive group A streptococcal infections has prompted a reexamination of the
      microorganism and its diverse clinical manifestations. A clonal basis for
      increased virulence expression is supported epidemiologically. As the incidence
      of streptococcal toxic shock-like syndrome appears to be increasing, it is
      imperative that clinicians become familiar with the presentation of this syndrome
      so they can diagnose and treat it in a timely and effective manner.

PMID- 7826101
TI  - Recurrent urticarial skin eruption since infancy. Muckle-Wells syndrome (MWS).

PMID- 7826102
TI  - Ivory-colored papules in a young boy. Mucopolysaccharidosis type II-B (Hunter's
      syndrome, mild).

PMID- 7826103
TI  - Punctate and linear angiectases. Anderson-Fabry disease (angiokeratoma corporis
      diffusum).

PMID- 7826104
TI  - Vision loss in a woman of American Indian heritage. Vogt-Koyanagi-Harada (VKH)
      syndrome (uveoencephalitis).

PMID- 7826105
TI  - Patch testing for corticosteroid allergy in the United States.

PMID- 7826106
TI  - Why block a small hole? The adverse effects of nasogastric tubes.

PMID- 7826107
TI  - Thoracic foregut duplications.

PMID- 7826108
TI  - Orthopaedic management of cerebral palsy.

PMID- 7826109
TI  - Is the risk of cancer increased in Asians living in the UK?
AB  - The pattern of cancer in white and Asian (Indian, Pakistani, and Bangladeshi)
      children living in the West Midlands Health Authority Region was investigated
      using age standardised incidence rates. Two sets of rates were calculated, a 10
      year rate (1982-91) using survey based estimates of the ethnic population and a
      four year rate (1989-92) using the ethnic population counts from the 1991 census.
      The 10 year rates showed a significantly higher annual incidence of cancer in
      Asian (159.1/million/year) than in white (130.8) children. The pattern of cancers
      in Asian children was different, with an excess of lymphomas and germ cell
      tumours, and a deficit of rhabdomyosarcomas. These findings were confirmed by the
      four year rates. Although underestimation of the Asian population probably
      contributes to the apparent excess, there remains cause for concern that UK Asian
      children may be at higher risk of cancer. Accurate ethnic population figures and
      confirmatory studies are urgently required.

PMID- 7826110
TI  - Delayed adolescent growth in homozygous sickle cell disease.
AB  - Analysis of the growth abnormalities in sickle cell disease has been limited by
      the lack of longitudinal observations in individuals, and by an inability to
      quantitate the observed patterns. To investigate the timing and pattern of the
      adolescent growth spurt, longitudinal observations of height from the Jamaican
      cohort study were fitted to a mathematical model of growth (Preece-Baines model
      1). The study included 44 children with homozygous sickle cell (SS) disease, 44
      age and sex matched subjects with sickle cell haemoglobin C (SC) disease, and 44
      age and sex matched controls with normal (AA) haemoglobin. Compared with AA
      controls, the onset of the adolescent growth spurt was delayed in SS disease by
      1.4 years (95% confidence interval 0.8 to 2.0) with no significant sex
      difference. The age at peak height velocity was delayed by 1.6 years (0.9 to 2.3)
      in SS compared with AA subjects but the adolescent growth of SS children was
      otherwise normal and there was no difference in the attained height by age 17.9
      years. The growth spurt was not delayed in SC disease. The age at menarche in
      girls with SS disease (mean (SD) 15.4 (1.3) years) was significantly later than
      girls with SC disease (13.7 (1.7) years) and those with AA haemoglobin (13.1
      (1.3) years) but these genotype differences were no longer significant after
      controlling for the delay in the adolescent growth spurt. The normally
      coordinated but slightly delayed pattern of growth and normal adult heights
      suggests a good prognosis for adolescent growth delay in SS disease. Most
      children with SS disease can therefore be reassured on the outcome of retarded
      adolescent growth.

PMID- 7826111
TI  - Human cytomegalovirus DNA in cerebrospinal fluid.
AB  - To determine the involvement of human cytomegalovirus (CMV) in conditions of
      neurological impairment, detection of CMV DNA was attempted in cerebrospinal
      fluid obtained from 45 neurologically affected children aged from 1 month to 17
      years by means of the polymerase chain reaction. Four patients (congenital CMV
      encephalopathy with West's syndrome, acute encephalitis, chronic epileptic
      encephalopathy, and lissencephaly) had CMV DNA in their cerebrospinal fluid. CMV
      DNA was absent in the cerebrospinal fluid of 11 neurologically unaffected
      controls aged from 1 month to 11 years. Three patients with acute CMV hepatitis
      had no CMV DNA in their cerebrospinal fluid. Among the four patients who had CMV
      DNA in their cerebrospinal fluid, two did not excrete CMV DNA or CMV antigen in
      the urine. The possible pathogenetic significance of CMV DNA in the cerebrospinal
      fluid is discussed. By applying the polymerase chain reaction to cerebrospinal
      fluid, the mode of brain invasion by CMV can be clarified further.

PMID- 7826112
TI  - Transhymenal cultures for sexually transmissible organisms.
AB  - Vaginal swabs were examined for sexually transmissible organisms in 238 girls
      seen over a 36 month period from July 1989 to June 1992 inclusive. Three groups
      were seen (age range 1.5-16.1 years), 165 in group 1 in whom there had been a
      disclosure of sexual abuse, 35 in group 2 where there was a strong suspicion of
      sexual abuse, and 38 with vulvovaginitis who formed group 3. The isolation of
      recognised sexually transmitted organisms was low; however, of group 1 19% were
      colonised with Gardnerella vaginalis compared with 3% of group 2 and 3% of group
      3. These figures show significant differences in the proportion of children in
      each group isolating only from children over the age of 8 years and in five of
      the six girls with Candida spp there was concern about sexual abuse.
      Vulvovaginitis in young children was not associated with vaginal candidiasis. The
      relation of findings to age is discussed and recommendations are made for testing
      procedures.

PMID- 7826113
TI  - Analysis of cells obtained by bronchial lavage of infants with respiratory
      syncytial virus infection.
AB  - To study the cellular infiltrate that occurs within the airways of infants with
      respiratory syncytial virus bronchiolitis, samples of airways secretions were
      obtained by bronchial lavage from the lower respiratory tract of infants
      ventilated for this condition and from the upper airway of non-intubated infants
      with this disorder using nasopharyngeal aspirates. Cytospin samples were prepared
      so that differential cell counts could be performed on the cells obtained and
      alkaline phosphatase-antialkaline phosphatase immunocytochemical analysis of
      lymphocyte subsets was carried out using a panel of monoclonal antibodies, which
      included anti-CD3, anti-CD4, anti-CD8, anti-CD19, and anti-TcR gamma delta.
      Results from the lower and upper airways were similar. Large numbers of
      inflammatory cells were obtained, of which neutrophils accounted for a median of
      93% in the upper airway and 76% in the lower airway. The numbers of CD8 positive
      cells detected were small and consistently less than CD4 positive cells, median
      CD4:CD8 ratios being 22.5:1 and 15:1 for the lower and upper airways. CD19
      positive cells were rarely observed and no gamma delta positive lymphocytes were
      detected. These results indicate that neutrophils probably play a major part in
      causing symptoms in these infants. They do not support the concept that excessive
      lymphocyte mediated cytotoxic activity is principally responsible for the
      pathology in respiratory syncytial virus bronchiolitis.

PMID- 7826114
TI  - Prevalence of cardiovascular malformations and association with karyotypes in
      Turner's syndrome.
AB  - The aim of the study was to establish the prevalence of cardiovascular
      malformations in females with Turner's syndrome and analyse possible associations
      with the various karyotypes. One hundred and seventy nine of 393 females who had
      Turner's syndrome diagnosed in Denmark were examined. Complete chromosome
      analysis was available in all cases. Clinical examination, electrocardiography,
      and echocardiography including Doppler were performed. The distribution of the
      various karyotypes was 45,X, 58%; mosaic monosomy X, 35%; and structural
      abnormalities of the X chromosome, 7%. In 46 (26%) of the females a total of 69
      cardiovascular malformations were found; aortic valve abnormality (18%) and
      aortic coarctation (10%) being the most common. There was a significant
      difference in the prevalence of cardiovascular malformations between 45,X and
      mosaic monosomy X (38% v 11%), primarily due to a significant difference in the
      prevalence of aortic valve abnormalities and aortic coarctation. Pulmonary valve
      abnormalities were seen only in females with mosaic monosomy X but the prevalence
      was low (3%). No patient with structural abnormalities of the X chromosome had
      cardiovascular malformations.

PMID- 7826115
TI  - Long term outcome after surgery for extrahepatic portal vein thrombosis.
AB  - The long term outcome of 21 children with extrahepatic portal hypertension
      secondary to portal vein thrombosis managed by surgical intervention was
      evaluated. Portosystemic shunts, used primarily in nine patients (eight central
      splenorenal, one mesocaval) after conservative treatment had failed, had no
      associated mortality and a 56% patency rate. Five of these shunted patients had
      no further bleeding episodes and did not show encephalopathic impairment. Direct
      attack procedures-portoazygos operation (four patients) was associated with
      significant complications, including one fatality. Other direct approaches
      oesophageal transection and variceal plication (five patients) had variable
      outcome. Splenectomy alone (three patients) ameliorated hypersplenism; however,
      further surgery for recurrent haemorrhage (two patients) was necessary.
      Endoscopic sclerotherapy controlled recurrent variceal bleeding (three patients)
      when it became available to the unit. Conservative treatment practised in five
      children had little success: two patients survived, two died from further
      haemorrhage, and one was lost to follow up. These results suggest that in centres
      without endoscopic expertise, and for patients who are sclerotherapy 'failures',
      surgery can be performed safely and achieve reasonable long term success rates in
      childhood extrahepatic portal hypertension.

PMID- 7826116
TI  - Diagnosis in Prader-Willi syndrome.
AB  - Thirty one patients with the putative diagnosis of Prader-Willi syndrome were
      reassessed clinically and by DNA analysis. Eleven patients were judged not to
      have Prader-Willi syndrome and 20 to have the condition. This was confirmed by
      DNA analysis in all but one case. The diagnosis of Prader-Willi syndrome,
      especially in early infancy, should be made with caution unless confirmed by
      molecular genetic studies.

PMID- 7826117
TI  - Fructosamine and glycated haemoglobin in the assessment of long term glycaemic
      control in diabetes.
AB  - Fructosamine and glycated haemoglobin were measured simultaneously in 147
      children with diabetes. If glycated haemoglobin is considered as the 'gold
      standard' for long term glycaemic control, then fructosamine is a poor indicator
      of actual glycated haemoglobin values, with wide 95% confidence (fiducial)
      limits. This shows that it is impossible to accurately predict glycated
      haemoglobin concentrations and therefore, by implication, longer term glycaemic
      control, from measurements of fructosamine. As the major studies on the
      prevention of microvascular complications in diabetes have used glycated
      haemoglobin levels to assess glycaemic control, it is suggested that this
      measurement should be used in all children with diabetes in preference to the
      measurement of fructosamine.

PMID- 7826118
TI  - Needle aspiration for suppurative post-BCG adenitis.
AB  - The effect of needle aspiration in suppurative post-BCG adenitis was studied.
      Nodes that had been aspirated (43 patients) regressed in 25 (58%) and 41 (95%)
      patients two and six months after aspiration. In the control group (34 patients)
      regression occurred in three (9%) and 22 (65%) patients. Spontaneous drainage
      with sinus tract formation was also significantly less in the aspirated group at
      six months (7% v 44%).

PMID- 7826119
TI  - Toledo type brachyolmia.
AB  - Brachyolmia is a form of spondylodysplasia that has not to the authors' knowledge
      been described in the UK. It may be a cause of short stature that is currently
      unrecognised. A case of an 11 year old boy with clinical, radiographic, and eye
      findings consistent with Toledo type brachyolmia is reported.

PMID- 7826120
TI  - Glycogenosis type IV: liver transplant at 12 years.
AB  - Hepatomegaly, the presenting feature of type IV glycogen storage disease at 20
      months of age, regressed during childhood. The patient remained asymptomatic
      until 12 years of age when, after an episode of shock, septicaemia, and
      spontaneous peritonitis, liver transplantation was successfully performed.

PMID- 7826121
TI  - Child health in Malaysia.

PMID- 7826122
TI  - Anthracyclines: cardiotoxicity and its prevention.

PMID- 7826124
TI  - Inpatient psychiatric treatment for diabetic teenagers.

PMID- 7826123
TI  - Management of acute bronchiolitis.

PMID- 7826125
TI  - Audit of guidelines for effective control of chemotherapy and radiotherapy
      induced emesis.
AB  - A system was devised to establish the optimum treatment for emesis for each
      individual child receiving cytotoxic treatment. Cytotoxic drugs were ranked on a
      scale (1-5), with antiemetic regimens correspondingly graded. An age division (<
      or = 5 years, > 5 years) was included. Cytotoxic treatment was given with co
      administration of the parallel antiemetic regimen. Failure to control emesis
      required administration of a stronger regimen as defined in the guidelines. A
      prospective clinical audit was performed to monitor the efficacy and utility of
      the system using diary cards to record episodes of nausea or vomiting, or both,
      completed by the patient or a parent and the nursing staff. The following audit
      criteria were set: (a) 80% control with first courses of chemotherapy; (b) 85%
      control with subsequent courses of similar chemotherapy; and (c) 90% lack of
      anticipatory nausea. Sixty children (< 18 years) received emetogenic cytotoxic
      drugs from February-June 1993. The criteria were satisfied in two of three
      categories, with 82% control for first courses of chemotherapy, 83% control for
      subsequent courses of chemotherapy, and 90% lack of anticipatory nausea. The
      guidelines were workable and acceptable overall. Minor modifications have been
      made subsequent to the audit to improve their efficacy further.

PMID- 7826126
TI  - Genital examination under ketamine sedation in cases of suspected sexual abuse.

PMID- 7826127
TI  - Genital examination under ketamine sedation in cases of suspected sexual abuse.

PMID- 7826128
TI  - Central nervous system tumours lack national studies.

PMID- 7826129
TI  - Recognising photosensitivity.

PMID- 7826130
TI  - Oral desensitisation in rheumatoid arthritis.

PMID- 7826131
TI  - Fever as an unusual presentation of a common condition.

PMID- 7826132
TI  - Neurological disturbances in ankylosing spondylitis.

PMID- 7826133
TI  - Utilisation of joint movement range in arboreal primates compared with human
      subjects: an evolutionary frame for primary osteoarthritis.
AB  - OBJECTIVE: To determine whether an arboreal lifestyle required full use of
      movement ranges underutilised in nine joint groups in humans, because under
      utilisation of available movement range may be associated with susceptibility to
      primary osteoarthritis. METHODS: Utilisation of the nine joint groups was studied
      in two species of primate exercising in a simulated arboreal environment, using
      'focal animal' observation techniques supplemented by telephoto photography and
      by review of archival material from other sources. Fifteen apes were observed
      over a total observation period of 20.2 man-hours and 152 films were analysed for
      utilisation of movement range. RESULTS: With one exception, all the movement
      ranges reported to be under-utilised in humans were fully utilised by the apes in
      climbing activities. The exception, metacarpophalangeal extension, was an
      essential component of the chimpanzee ground progression mode of knuckle walking.
      CONCLUSIONS: The underused movement range in several human joints is explicable
      as residual capacity from a semiarboreal lifestyle. If the correlation with
      primary osteoarthritis is confirmed, it suggests that the disease may reflect a
      disparity between inherited capacity and current need. The significance of the
      result lies in its implication that primary osteoarthritis may be preventable.

PMID- 7826134
TI  - Relationship between weakness and muscle wasting in rheumatoid arthritis.
AB  - OBJECTIVE: To relate weakness of grip to loss of forearm muscle bulk, hand joint
      deformity, and hand joint tenderness in patients with rheumatoid arthritis (RA).
      METHODS: Using anthropometric data we have estimated the anatomical cross
      sectional area (CSA) of forearm muscles in 100 subjects with RA compared with 100
      aged and sex-matched normal subjects. We also recorded hand joint tenderness
      using a modification of the Ritchie articular index, and a simple index of hand
      joint deformity. RESULTS: We found a significant reduction in anatomical CSA in
      RA (forearm CSA in normal subjects 29.7 cm2 and in RA 25.9 cm2; p = 0.002). In
      simple linear regression we found that 46.3% of the variation in grip strength in
      normal subjects was explained by variation in muscle CSA; in RA this figure
      decreased to 33.4%. Adding terms for joint deformity and pain in a multiple
      regression model improved the amount of variation explained to 37.9%.
      CONCLUSIONS: Although there is significant muscle wasting in RA, it is likely
      that reduction in strength is also attributable to joint deformity and pain
      leading to inhibition of grip directly and, indirectly, by arthrogenous muscle
      inhibition. Doubts remain about the quality of muscle in RA.

PMID- 7826135
TI  - Urine neopterin: a new parameter for serial monitoring of disease activity in
      patients with systemic lupus erythematosus.
AB  - OBJECTIVE: To investigate the role of serial measurement of urine neopterin
      concentration in monitoring the progression of systemic lupus erythematosus (SLE)
      disease activity scored using the British Isles Lupus Assessment Group (BILAG)
      index. METHODS: We followed prospectively 68 unselected SLE patients for a total
      of 464 patient months during which 233 separate assessments were carried out. At
      each assessment, urine neopterin, determined by high performance liquid
      chromatography, together with erythrocyte sedimentation rate (ESR) and plasma C3,
      C4, and C3d were measured and the SLE disease activity scored by a single
      observer. Serial data sets were analysed using time series modelling techniques.
      RESULTS: Single time point analysis showed a significant increase in urine
      neopterin concentrations in 14 patients who suffered flares of their disease
      during the study period (p = 0.02). Thirty patients with active disease went into
      disease remission with significant decreases in their urine neopterin values (p =
      0.02). In the time series analysis, a statistically significant association was
      found between serial concentrations of urine neopterin and BILAG score (r = 0.6,
      p < 0.05); no other study parameter (ESR and serum C3, C4, and C3d) mirrored SLE
      disease activity as effectively. CONCLUSIONS: This study provides initial
      evidence that changes in urine concentrations of neopterin are significantly
      correlated with fluctuations in disease activity over time, scored using the
      BILAG index, amongst individual patients with SLE. Consequently, serial urine
      neopterin measurements appear to be clinically useful for monitoring disease
      activity and may contribute substantially to therapeutic decision making in these
      patients.

PMID- 7826136
TI  - Polymerase chain reaction fails to incriminate exogenous retroviruses HTLV-I and
      HIV-1 in rheumatological diseases although a minority of sera cross react with
      retroviral antigens.
AB  - OBJECTIVES: To investigate the presence of antibodies to HTLV and HIV retroviral
      antigens in the rheumatological diseases rheumatoid arthritis (RA),
      polymyositis/dermatomyositis (PM/DM), primary Sjogren's syndrome (pSS), and
      systemic lupus erythematosus (SLE), and to use polymerase chain reaction (PCR) to
      seek these exogenous retroviruses in proviral form in cellular DNA from these
      patients. METHODS: Thirty patients with active RA, 13 with PM, 14 with pSS and
      five with SLE were recruited and their sera tested for antibodies to HTLV-I in
      enzyme linked immunosorbent assay (ELISA) and Western blot analysis.
      Seropositivity to HIV-1 was also sought. DNA was extracted from peripheral blood
      lymphocytes, synovial tissue and muscle biopsies and tested by polymerase chain
      reaction using consensus primers for HTLV-I and HIV-1. RESULTS: In HTLV-I ELISA,
      nine rheumatological sera (4/30 RA, 3/13 PM/DM and 2/5 SLE patients) were
      considered positive; 14 from pSS patients and 30 from normal subjects were
      negative. In a control group which included osteoarthritis, Crohn's disease and
      bacterial endocarditis patients, only two of 80 proved positive in this system.
      Validation of these sera by Western blotting generally revealed weak reactivity
      against a variety of HTLV-I antigens. PCR of genomic DNA derived from patients'
      peripheral blood mononuclear cells did not reveal the presence of HTLV-I and HIV
      1 target sequences. CONCLUSIONS: This study shows that PCR precludes HTLV-I and
      HIV-1 infection as causative agents in these rheumatological diseases although a
      minority of patients possess antibodies that are weakly cross-reactive with
      retroviral antigens.

PMID- 7826137
TI  - HLA-B alleles and complotypes in Mexican patients with seronegative
      spondyloarthropathies.
AB  - OBJECTIVES: To analyse major histocompatibility complex (MHC) haplotypes in
      Mexican mestizo patients with seronegative spondyloarthropathies (SSpA) and
      normal controls, to discover if there are other antigens, besides B27, in the HLA
      region that might show association with the disease. METHODS: The study included
      100 Mexican mestizo patients with SSpA and 200 of their first degree relatives.
      These groups were compared with 85 ethnically matched controls. The class I and
      class III MHC antigens were obtained by standard methods. The significance of
      differences between patients and controls was tested by chi 2 analysis; linkage
      disequilibrium among the different alleles in each haplotype was estimated by
      computing delta values. RESULTS: We found a significantly increased frequency of
      the HLA-B27 antigen (pcorr. = 1 x 10(-5), odds ratio (OR) = 33.4, 95% confidence
      interval (CI) = 9.3-142.0). In the group of 45 SSpA patients negative for the B27
      antigen, independent increased frequencies of HLA-B49 antigen (pcorr. = 0.03, OR
      = 6.5, 95% CI = 1.5-32.8)) and the FC31 complotype (pcorr. = 0.04, OR = 3.7, 95%
      CI = 1.2-11.1) were found. Significant delta values were obtained for the
      [B27;SC30] haplotype (p = 0.0005) but not for haplotypes marked by the FC31
      complotype. HLA-B antigens on the homologous chromosome in B27 positive patients
      were mainly HLA-B51 (18%) and HLA-B60 (16%); however, the observed genotypes
      B27/B51 and B27/B60 were not significantly different than expected from the
      allele frequencies alone. CONCLUSIONS: These data suggest that in Mexicans
      additional genes within the MHC region besides the HLA-B27 antigen, might be
      related to the genetic susceptibility for developing SSpA. Relevant antigens
      included the HLA-B49 and the FC31 complotype.

PMID- 7826138
TI  - Gout in black South Africans: a clinical and genetic study.
AB  - OBJECTIVE: To define the clinical characteristics of gout and determine if there
      were any genetic associations with gout in black South Africans. METHODS: The
      records of 107 patients with gout seen over a five year period were
      retrospectively analysed. The HLA class I and class II antigens were studied in a
      prospective survey of 46 patients. RESULTS: The male to female ratio was 6.6:1.
      The diagnosis of gout was based on identification of monosodium urate crystals
      from the synovial fluid, synovial tissue or tophaceous material in 62 patients
      (58%) and on clinical criteria in the remaining 45 patients (42%). The mode of
      presentation was monoarthritis in 40 patients (37.4%), pauciarthritis in 30 (28%)
      and polyarthritis in 37 (34.6%). The joints which were most frequently involved
      were the knee in 91 patients (85%), the first metatarsophalangeal in 80 (74.8%)
      and the ankle in 66 (61.7%). A secondary cause was identified in 52 patients
      (48.6%) (diuretic therapy in 48 patients and chronic renal impairment in four);
      55 patients (51.4%) had primary gout. The genetic study showed an increased
      frequency of HLA-B14 in patients with primary gout compared with controls.
      CONCLUSIONS: Gout is more common in black Africans than previously recognised and
      frequently presents with involvement of more than one joint. There was an
      increased frequency of HLA-B14 in patients with primary gout but the clinical
      significance of this is uncertain.

PMID- 7826139
TI  - Plasma TGF beta in systemic sclerosis: a cross-sectional study.
AB  - OBJECTIVES: To determine whether the active 25 kDa form of the fibrogenic
      cytokine transforming growth factor beta (TGF beta) can be detected in plasma
      from patients with systemic sclerosis and to examine the relationship between
      plasma TGF beta and clinical markers of disease severity and serum concentrations
      of the aminoterminal peptide of type III procollagen (PIIINP) (a laboratory
      marker of the fibrotic process). METHODS: A cross sectional study was made of 39
      patients with systemic sclerosis (11 diffuse and 28 limited), nine patients with
      primary Raynaud's disease and 60 healthy controls. TGF beta 1 and TGF beta 2 were
      measured by enzyme linked immunosorbent assay (ELISA) (sensitivity 100 pg/ml) and
      PIIINP by radioimmunoassay. RESULTS: TGF beta 1 was detected in plasma from six
      of 39 patients with systemic sclerosis but not in any patient with primary
      Raynaud's disease or healthy controls. TGF beta 2 was not detected in plasma from
      patients or controls. No clear relationship was demonstrated between TGF beta 1,
      clinical features or PIIINP concentrations. CONCLUSIONS: The 25 kDa form of TGF
      beta 1 can be detected in the plasma of some patients with systemic sclerosis.
      This provides limited support for the hypothesis that this cytokine plays a role
      in the pathogenesis of this disease. However, longitudinal studies, particularly
      in early diffuse disease, are required to clarify the relationship between
      circulating TGF beta 1 and disease activity.

PMID- 7826140
TI  - Increased serum proMMP-3 in inflammatory arthritides: a potential indicator of
      synovial inflammatory monokine activity.
AB  - OBJECTIVE: To investigate if the increased concentrations of stromelysin (MMP-3)
      found in the synovial fluid (SF) of patients with various arthritides reflect the
      concentrations in the circulation. METHODS: Using a double antibody ELISA, we
      have measured proMMP-3 concentrations in sera from these patient groups and in
      others with a heightened acute phase response (APR) as a result of multiple organ
      failure. RESULTS: The median serum concentration of proMMP-3 was increased by up
      to ninefold in the inflammatory arthritides, but not in osteoarthritis or in
      patients with a heightened APR resulting from a non-chronic inflammatory
      condition. CONCLUSION: In chronic inflammatory diseases such as rheumatoid
      arthritis, serum proMMP-3 may prove to be a more specific indicator of monokine
      activity than currently available serum markers.

PMID- 7826141
TI  - Age and sex influences on fall characteristics.
AB  - OBJECTIVE: To investigate age and sex influences on fall characteristics.
      METHODS: A total of 1243 subjects (517 males and 726 females) aged 50 years and
      over and drawn from population based sampling frames were invited to complete an
      interviewer administered questionnaire concerning descriptive characteristics of
      falls experienced in the previous four months. Information collected included
      details about the part of the body to strike the ground, direction of the fall,
      level of trauma and whether or not injury or fracture was sustained. RESULTS: One
      hundred and seventy two subjects reported a fall in the previous four months.
      Restricting analysis to the 142 subjects who fell from a standing height or less,
      females aged 50-64 years were more than twice as likely to fall onto their hand
      compared with older females (odds ratio (OR) = 2.2; 95% confidence interval (CI)
      0.8 to 6.2) and at all ages (50+) were more than three times as likely to fall on
      their hip compared with males (OR = 3.4; 95% CI 1.0 to 11.5). Compared with older
      males, males aged 50-64 were more likely to fall sideways (OR = 5.1; 95% CI 1.5
      to 17.4) and less likely to fall forwards (OR = 0.4; 95% CI 0.1 to 1.1).
      CONCLUSION: There is a potentially clinically important variation in fall type by
      age and sex. In particular, this variation might explain patterns of occurrence
      of hip and Colles' fracture.

PMID- 7826143
TI  - The Cambridge dilemma.

PMID- 7826142
TI  - Increased mitogenic activity of scleroderma serum: inhibitory effect of human
      recombinant interferon-gamma.
AB  - OBJECTIVES: To investigate the role of platelet activation in the development of
      systemic sclerosis and the role of interferon-gamma (IFN gamma) in the inhibition
      of mitogenic activity induced by whole blood serum of patients with systemic
      sclerosis. METHODS: The mitogenic activity of whole blood serum in the absence or
      presence of different concentrations of IFN gamma (a potent inhibitor of induced
      collagen synthesis in dermal fibroblasts) and platelet-poor plasma derived serum
      were tested on human dermal fibroblasts by measuring incorporation of
      [3H]thymidine. Platelet activation was determined by quantification of plasma
      beta-thromboglobulin (beta-TG) using a beta-TG radioimmunoassay kit. RESULTS: The
      mitogenic activity was significantly increased in whole blood serum and in
      platelet-poor plasma derived serum of the patients compared with controls. In
      contrast, no significant increase in beta-TG concentration was observed in
      scleroderma platelet-poor plasma compared with control. Recombinant human IFN
      gamma had a greater inhibitory effect on the mitogenic activity induced by whole
      blood serum of patients than on that produced with control sera, at any
      concentration of IFN gamma tested. CONCLUSIONS: Our results suggest that
      mitogenic activity observed in the plasma of sclerodermic patients could
      originate from cells other than platelets and could be involved in the
      development of fibrosis. The potent inhibitory effect of IFN gamma on this
      proliferative activity may account for the beneficial effect of this cytokine in
      the treatment of progressive systemic sclerosis.

PMID- 7826144
TI  - Silicon nephropathy and myeloperoxidase antibodies.

PMID- 7826145
TI  - Rheumatoid arthritis in black Americans.

PMID- 7826146
TI  - Dactylitis also involving the synovial sheaths in the palm of the hand.

PMID- 7826147
TI  - The repair of inguinal hernias.

PMID- 7826148
TI  - Kinetics of endotoxin and tumor necrosis factor appearance in portal and systemic
      circulation after hemorrhagic shock in rats.
AB  - OBJECTIVE: This study was performed to investigate gut-derived bacterial
      translocation and the time course of endotoxin (lipopolysaccharide [LPS]) and
      tumor necrosis factor (TNF) appearance, both in portal and systemic circulation.
      SUMMARY BACKGROUND DATA: The significance of intestinal bacteria/endotoxin
      translocation or TNF formation in the development of systemic sepsis has been
      disputed. METHODS: A rat model of hemorrhagic shock (30-35 mm Hg for 90 min) and
      resuscitation was used. RESULTS: Bacterial translocation was histologically
      observed in the small intestinal wall 30 minutes after resuscitation. A
      significant increase in LPS concentrations was found in the portal vein (91.7 +/-
      30.6 pg/mL) at 90 minutes, which remained steady until 150 minutes after shock.
      Lipopolysaccharide increased in the systemic circulation, the levels became
      significant at 120 minutes, and peaked (66.5 +/- 39.2 pg/mL) 150 minutes after
      shock. Tumor necrosis factor concentrations were found to be significantly
      elevated in both portal and systemic circulation (75.6 +/- 22.1 vs. 58.4 +/- 14.1
      pg/mL) at 90 minutes post-shock. Although there was no further increase in TNF
      concentration in the portal blood. TNF peaked (83.5 +/- 17.7 pg/mL) in systemic
      circulation at 120 minutes and still was markedly increased at 150 minutes post
      shock. In addition, higher LPS and TNF concentrations in systemic circulation
      were found in the nonsurvivors than in the surviving animals at the end of
      resuscitation. CONCLUSIONS: These results suggest that hemorrhagic shock may lead
      to early bacterial translocation in the intestinal wall and transient access of
      gut-derived LPS and LPS-induced mediators into the circulation predominantly via
      the portal circulation.

PMID- 7826149
TI  - Evaluation of the contralateral breast--the role of biopsy at the time of
      treatment of primary breast cancer.

PMID- 7826150
TI  - Tumor thickness.

PMID- 7826151
TI  - Selective management of gastroschisis.

PMID- 7826152
TI  - Incidence of adhesions between intra-abdominal viscera and a polypropylene mesh
      prosthesis.

PMID- 7826153
TI  - Failure of silver impregnated subcutaneous cuffs to prevent intravascular
      catheter infections in cancer patients.

PMID- 7826154
TI  - Management of common bile duct stones in the era of laparoscopic cholecystectomy.

PMID- 7826155
TI  - Laparoscopic versus conventional appendectomy.

PMID- 7826156
TI  - Reoperative pancreaticoduodenectomy.

PMID- 7826157
TI  - Pulmonary transplantation.
AB  - OBJECTIVE: More than 2700 lung transplants have been performed since the initial
      clinical success in 1983. The evolution in the techniques of lung transplantation
      and patient management and the effects on results are reviewed. SUMMARY
      BACKGROUND DATA: Improvements in donor management, lung preservation, operative
      techniques, immunosuppression management, infection prophylaxis and treatment,
      rejection surveillance, and long-term follow-up have occurred in the decade
      following the first clinically successful lung transplant. A wider spectrum of
      diseases and patients treated with lung transplant have accentuated the shortage
      of suitable lung donors. The organ shortage has led to the use of marginal donors
      and a limited experience using living, related donors. METHODS: Changes in
      techniques and patient selection and management are reviewed and controversial
      issues and problems are highlighted. RESULTS: One-year survival of greater than
      90% for single-lung transplant recipients and greater than 85% for bilateral lung
      transplant recipients have been achieved. Complications caused by airway
      complications has been reduced greatly. Obliterative bronchiolitis develops in
      20% to 50% of long-term survivors and is the leading cause of morbidity and
      mortality after the first year after transplant. CONCLUSIONS: Lung
      transplantation has evolved into an effective therapy for a wide variety of
      causes of end-stage lung disease. Wider applicability requires solutions to the
      problems of donor shortage and development of obliterative bronchiolitis.

PMID- 7826158
TI  - Peritonectomy procedures.
AB  - OBJECTIVE: New surgical procedures designed to assist in the treatment of
      peritoneal surface malignancy were sought. BACKGROUND: Decisions regarding the
      treatment of cancer depend on the anatomic location of the malignancy and the
      biologic aggressiveness of the disease. Some patients may have isolated intra
      abdominal seeding of malignancy of limited extent or of low biologic grade. In
      the past, these clinical situations have been regarded as lethal. METHODS: The
      cytoreductive approach may require six peritonectomy procedures to resect or
      strip cancer from all intra-abdominal surfaces. RESULTS: These are greater
      omentectomy-splenectomy; left upper quadrant peritonectomy; right upper quadrant
      peritonectomy; lesser omentectomy-cholecystectomy with stripping of the omental
      bursa; pelvic peritonectomy with sleeve resection of the sigmoid colon; and
      antrectomy. CONCLUSIONS: Peritonectomy procedures and preparation of the abdomen
      for early postoperative intraperitoneal chemotherapy were described. The author
      has used the cytoreductive approach to achieve long-term, disease-free survival
      in selected patients with peritoneal carcinomatosis, peritoneal sarcomatosis or
      mesothelioma.

PMID- 7826159
TI  - Laparoscopic inguinal herniorrhaphy. Results of a multicenter trial.
AB  - OBJECTIVE: The purpose of this study was to determine if laparoscopic inguinal
      herniorrhaphy represents a viable alternative to the conventional repair and to
      assess whether a prospective randomized controlled trial comparing both
      procedures is warranted. METHODS: Three types of laparoscopic inguinal
      herniorrhaphies (transabdominal preperitoneal [TAPP], intraperitoneal onlay mesh
      [IPOM], and totally extraperitoneal [EXTRA]) were studied in a phase II design.
      Twenty-one investigators from 19 institutions participated. Approval from the
      local human research committee was required at each institution before patients
      could be enrolled. RESULTS: There were 686 patients with 869 hernias; 366 (42.1%)
      were direct, 414 (47.6%) were indirect, 22 (2.5%) were femoral, and 67 (7.7%)
      were combination hernias. The TAPP procedure was used for 562 hernias, the IPOM
      was used for 217 hernias, and the EXTRA was used for 87 hernias. Sixty-one
      patients had additional abdominal procedures performed at the time of laparoscopy
      without any adverse affects on their herniorrhaphies. The overall recurrence rate
      was 4.5%, with a minimum follow-up of 15 months. Complications were divided into
      the following three groups: 1) those related to laparoscopy, 2) those related to
      the patient, and 3) those related to the herniorrhaphy. Complications related to
      the laparoscopy occurred in 5.4% of patients; bleeding or abdominal wall
      hematomas occurred 31 times, (two patients required transfusion); one patient had
      bowel perforation, which was sutured laparoscopically; a bladder injury required
      laparotomy for management. Patient complications occurred in 6.7%. The majority
      involved the urinary tract (5.8%). Two patients required secondary abdominal
      procedures for adhesions, one for pain in the right lower quadrant and the other
      for adhesive small bowel obstruction. Postoperative myocardial infarction on day
      5 resulted in the only operative mortality, for a rate of 0.1%. Complications
      related to the herniorrhaphy itself occurred in 17.1%. Most of these were minor,
      consisting of transient groin pain (3.5%), seroma (3.5%), transient leg pain
      (3.3%), hematoma (1.5%), or transient cord or testicular problems (0.9%). The
      incidence of leg pain decreased dramatically as surgeons became more familiar
      with the anatomy of the nerve supply to the groin when viewed laparoscopically.
      Ninety-three percent of patients were discharged within 24 hours of their
      operations. CONCLUSIONS: Laparoscopic inguinal herniorrhaphy is an effective
      method to correct an inguinal hernia. It can be offered safely to patients
      undergoing other abdominal procedures. The TAPP, IPOM, and EXTRA procedures
      appear to be equally effective. A controlled randomized trial is needed to
      compare this procedure with conventional inguinal herniorrhaphy.

PMID- 7826160
TI  - The effects of regionalization on cost and outcome for one general high-risk
      surgical procedure.
AB  - PURPOSE: The effects of regionalization of tertiary care were studied by
      analyzing cost and outcome for pancreaticoduodenectomies in a state in which the
      majority of these high-risk procedures were performed in one hospital. METHODS:
      Using Maryland inpatient discharge data via a retrospective study, the authors
      compared cost and outcome data for a hospital with more than one half of the
      cases in the state to all other hospital providers as a group and with smaller
      groupings according to the volume of procedures performed. RESULTS: Hospital
      mortality, length of stay, and costs were significantly less at the high-volume
      regional medical center when compared with all other hospitals. Mortality and
      cost increased as volume decreased when hospitals were grouped according to
      volume. CONCLUSIONS: An academic medical center, functioning as a high-volume
      regional provider, can deliver tertiary care services with improved outcomes at
      lower costs than community hospitals.

PMID- 7826161
TI  - Normalization of tumor-induced increases in hepatic amino acid transport after
      surgical resection.
AB  - BACKGROUND: The liver of the host with cancer requires increased amounts of amino
      acids to support the synthesis of glucose and key defense proteins. To study the
      effect of the growing tumor on hepatic amino acid uptake, the authors measured
      hepatic transport activity in tumor-bearing rats and in rats at various times
      after tumor resection. METHODS: Fischer-344 rats were implanted subcutaneously
      with methylcholanthrene-induced fibrosarcoma cells (MCA sarcoma). When the tumors
      reached 10% of body weight, hepatic amino acid transport activity was assayed or
      the animals underwent surgical removal of the tumor. In animals that underwent
      tumor excision, livers were removed at 1, 3, or 5 days post-resection, and
      hepatic plasma membrane vesicles (HPMVs) were prepared. Nontumor-bearing pair-fed
      rats undergoing sham implantation or sham resection served as controls. System N
      (glutamine), System A (MeAIB), and System y+ (arginine) transport activity were
      assayed, which allowed the authors to compare differences in tumor-induced rates
      of transport and the influence of resection on transport activity. RESULTS:
      System A transport activity was unaltered by tumor growth. In contrast, the
      presence of the growing tumor increased arginine and glutamine uptake by the
      liver. Hepatic glutamine transport remained elevated for 5 days after tumor
      resection, although by postoperative day 5 there was a trend toward
      normalization. In contrast, arginine transport remained increased by twofold
      onpost-resection day 1 and had normalized by postoperative day 3. The enhanced
      arginine transport was a result of an increase in maximal transport velocity
      (Vmax) rather than a change in carrier affinity. CONCLUSIONS: Increases in
      hepatic amino acid transport normalize within several days of tumor resection,
      indicating a key role for the tumor in the induction of this response. The
      observation that hepatic glutamine transport activity remains augmented after
      tumor resection longer than any other transporter studied suggests a key role for
      this amino acid in overall hepatic nitrogen metabolism and may partially explain
      the persistent glutamine depletion that is characteristic of the tumor-bearing
      host.

PMID- 7826162
TI  - Long-term survival after resection for ductal adenocarcinoma of the pancreas. Is
      it really improving?
AB  - OBJECTIVE: The authors review their recent experience with resected pancreatic
      ductal adenocarcinoma. SUMMARY BACKGROUND DATA: Ductal adenocarcinoma of the
      pancreas has traditionally had a 5-year survival rate less than 10% after
      curative resection. Recently, several groups have reported markedly improved 5
      year survival rates (approaching 25%) for patients undergoing curative resection.
      METHODS: Institutional experience with 186 consecutive patients (1981-1991) with
      pathologic diagnoses of ductal adenocarcinoma undergoing pancreatic resection was
      reviewed. Histologic specimens of all 3-year survivors (n = 31) were re-reviewed
      by two pathologists, one internal and one external; nonductal pancreatic cancers
      then were excluded. RESULTS: After histologic re-review, 12 patients did not have
      ductal adenocarcinoma, leaving a total of 174 patients for analysis (102 men, 72
      women; mean age 63 years, range 34-82 years). Mean follow-up was 22 months (range
      4-109). Classical pancreaticoduodenectomy was performed in 71%, pylorus
      preserving resection in 9%, and total pancreatectomy in 20%. Hospital mortality
      was 3%. Twenty-eight patients (16%) had macroscopically incomplete resections; 98
      (56%) had lymph node metastases within the resected specimens, and 21 patients
      (12%) had extensive perineural invasion. Overall actuarial 5-year survival was
      6.8%. Five-year survival was greater for node-negative versus node-positive
      patients (14% vs. 1%, p < 0.001), and for smaller (< 2 cm) versus larger tumors
      (20% vs. 1%, p < 0.001). The 5-year survival for the subset of patients with
      negative nodes and no perineural or duodenal invasion (69 patients) was 23% (p <
      0.001). Mean survival of the 12 excluded patients was 53 +/- 7 months compared
      with 17.5 +/- 1 months in the 174 patients with ductal pancreatic cancer.
      CONCLUSIONS: Five-year survival for patients undergoing pancreatic resection for
      lesions deemed to be clinically "curable" intraoperatively and histologically
      reviewed/confirmed to be ductal adenocarcinoma of the pancreas is approximately
      7%. Survival is greater (23%) in the subset of patients with negative nodes and
      no duodenal or perineural invasions. Pathologic review of all patients with
      pancreatic ductal cancer adenocarcinoma is mandatory if survival data are to be
      meaningful.

PMID- 7826163
TI  - Conservative surgery for low rectal carcinoma after high-dose radiation.
      Functional and oncologic results.
AB  - OBJECTIVE: Using a prospective, nonrandomized study, the authors evaluated the
      morbidity and functional and oncologic results of conservative surgery for cancer
      of the lower third of the rectum after high-dose radiation. SUMMARY BACKGROUND
      DATA: Colo-anal anastomosis has made sphincter conservation for low rectal
      carcinoma technically feasible. The limits to conservative surgery currently are
      oncologic rather than technical. Adjuvant radiotherapy has proven its benefit in
      terms of regional control, with a dose relationship. METHODS: Since June 1990, 27
      patients with distal rectal adenocarcinoma were treated by preoperative
      radiotherapy (40 + 20 Gy delivered with three fields) and curative surgery. The
      mean distance from the anal verge was 47 mm (27-57 mm), and none of the tumors
      were fixed (15 T2, 12 T3). RESULTS: Mortality and morbidity were not increased by
      high-dose preoperative radiation. Twenty-one patients underwent conservative
      surgery (78%-17 total proctectomies and colo-anal anastomoses, 4 trans-anal
      resections). After colo-anal anastomosis, all patients with colonic pouch had
      good results; two patients had moderate results and one patient had poor results
      after straight colo-anal anastomosis. With a mean follow-up of 24 months, the
      authors noted 1 postoperative death, 2 disease-linked deaths, 1 controlled
      regional recurrence, 2 evolutive patients with pulmonary metastases, and 21
      disease-free patients. CONCLUSIONS: These first results confirm the possibility
      of conservative surgery for low rectal carcinoma after high-dose radiation. A
      prospective, randomized trial could be induced to determine the real role of the
      20 Gy boost on the sphincter-saving decision.

PMID- 7826164
TI  - Pathologic support for limited hepatectomy in the treatment of liver metastases
      from colorectal cancer.
AB  - OBJECTIVE: The authors determined an appropriate surgical treatment for liver
      metastases from colorectal cancers. Clinicopathologic features of metastatic
      lesions of colorectal cancers were studied. SUMMARY BACKGROUND DATA: Major
      hepatic resection is the usual procedure for treatment of hepatic metastases from
      colorectal cancers. METHODS: Forty consecutive patients who underwent hepatic
      resections were prospectively studied, for a total of 89 metastatic liver tumors.
      RESULTS: Metastatic tumor often extended along Glisson's capsule, including
      invasion to the portal vein (9 cases), the hepatic vein (3 cases), the bile duct
      (16 cases), and the nerve (6 cases). The main tumor had small satellite nodules
      in only one patient, and there were no microscopic deposits in the parenchyma,
      even within 10 mm from the metastatic tumors. Fibrous pseudocapsule formation was
      observed in 28 patients. DISCUSSION: The rarity of intrahepatic metastasis from
      metastatic tumor supports nonanatomic limited hepatic resection as the procedure
      of choice for metastatic colorectal cancer in the liver. The spread via Glisson's
      capsule should be taken into consideration for complete tumor clearance.

PMID- 7826165
TI  - Liquid ventilation improves pulmonary function, gas exchange, and lung injury in
      a model of respiratory failure.
AB  - OBJECTIVE: The authors evaluated gas exchange, pulmonary function, and lung
      histology during perfluorocarbon liquid ventilation (LV) when compared with gas
      ventilation (GV) in the setting of severe respiratory failure. BACKGROUND: The
      efficacy of LV in the setting of respiratory failure has been evaluated in
      premature animals with surfactant deficiency. However, very little work has been
      performed in evaluating the efficacy of LV in older animal models of the adult
      respiratory distress syndrome (ARDS). METHODS: A stable model of lung injury was
      induced in 12 young sheep weighing 16.4 +/- 3.0 kg using right atrial injection
      of 0.07 mL/kg of oleic acid followed by saline pulmonary lavage and bijugular
      venovenous extracorporeal life support (ECLS). For the first 30 minutes on ECLS,
      all animals were ventilated with gas. Animals were then ventilated with either 15
      mL/kg gas (GV, n = 6) or perflubron ([PFC], LV, n = 6) over the ensuing 2.5
      hours. Subsequently, ECLS was discontinued in five of the GV animals and five of
      the LV animals, and GV or LV continued for 1 hour or until death. MAIN FINDINGS:
      Physiologic shunt (Qps/Qt) was significantly reduced in the LV animals when
      compared with the GV animals (LV = 31 +/- 10%; GV = 93 +/- 4%; p < 0.001) after 3
      hours of ECLS. At the same time point, pulmonary compliance (CT) was
      significantly increased in the LV group when compared with the GV group (LV =
      1.04 +/- 0.19 mL/cm H2O/kg; GV = 0.41 +/- 0.02 mL/cm H2O/kg; p < 0.001). In
      addition, the ECLS flow rate required to maintain the PaO2 in the 50- to 80-mm Hg
      range was substantially and significantly lower in the LV group when compared
      with that of the GV group (LV = 14 +/- 5 mL/kg/min; GV = 87 +/- 15 mL/kg/min; p <
      0.001). All of the GV animals died after discontinuation of ECLS, whereas all the
      LV animals demonstrated effective gas exchange without extracorporeal support for
      1 hour (p < 0.01). Lung biopsy light microscopy demonstrated a marked reduction
      in alveolar hemorrhage, lung fluid accumulation, and inflammatory infiltration in
      the LV group when compared with the GV animals. CONCLUSION: In a model of severe
      respiratory failure, LV improves pulmonary gas exchange and compliance with an
      associated reduction in alveolar hemorrhage, edema, and inflammatory infiltrate.

PMID- 7826167
TI  - [Aleicid, a new natural insecticide isolated from a culture of Streptomyces
      aurantuacus. Component composition, physicochemical and biological properties of
      the aleicid major components].
AB  - The component composition of aleicid, a complex product with insecticidal
      activity was studied. It was shown by TLC and HPLC that aleicid is a complex of
      components two of which are basic. The major components of aleicid were
      identified with pyericidines of groups B and C.

PMID- 7826168
TI  - [Sorption of aminoglycoside antibiotics from unfiltered culture fluid].
AB  - Sorption of aminoglycosides such as sisomicin, gentamicin, kanamycin and
      streptomycin from the non-filtrated fermentation broth by carboxylic cation
      exchange resins under the static conditions was studied. The optimal conditions
      for the sorption of the aminoglycosides and their subsequent desorption were
      determined (the ratio of the volumes of the sorbent and fermentation broth and
      the time of the sorption and desorption).

PMID- 7826166
TI  - Anticancer chemosensitivity changes between the original and recurrent tumors
      after successful chemotherapy selected according to the sensitivity assay.
AB  - OBJECTIVE: The authors compare and characterize the changes in chemosensitivity
      between the original tumors before chemotherapy and recurrent tumors after
      responses. SUMMARY BACKGROUND DATA: The drug resistance in clinical chemotherapy
      appears to be different from that in experimental chemotherapy, and the profile
      and mechanisms of clinical drug resistance in recurrent tumors, especially after
      successful chemotherapy has scarcely been studied. METHODS: Applied
      chemotherapies were selected out of four agents, cisplatin (CDDP), adriamycin
      (ADR), mitomycin-C (MMC) and 5-fluorouracil (5-FU), singly or in combinations by
      a DNA synthesis inhibition assay, by which the sensitivity of recurrent tumors
      was assessed. Responses were defined according to the standard criteria, and
      successful chemotherapy indicates complete response (CR) or partial response (PR)
      for solid tumors and complete disappearance for malignant effusion. RESULTS: In
      37 patients, the effectiveness of four agents were compared between before
      chemotherapy and after recurrence, and the response lasted between 2 and 26
      months (mean +/- SD, 7.7 +/- 5.5). The results suggest that locally recurred
      tumors may become resistant to the agents previously administered; by contrast,
      distantly recurred tumors may not necessarily become resistant to the agents
      administered. The recurrent tumors are suggested to be sensitive to the agents as
      follows: locally recurrent solid tumors, 5-FU; distantly recurrent solid tumors,
      5-FU and CDDP; locally recurrent effusion, CDDP; distantly recurrent effusion,
      ADR. Twenty-three of 37 recurrent tumors were re-treated with chemotherapies
      selected according to the sensitivity assay, singly or in combination with a
      biologic response modifier (BRM)--a streptococcal preparation, OK-432, or
      interferon-alpha. Responses were seen in 1 of 13 solid recurrent tumors and in 6
      of 10 recurrent effusions. Responses were seen only when the patients were
      treated with a combination of chemotherapy and BRM. CONCLUSION: There may be a
      notable differences in the basic biologic characteristics of tumor cells with
      respect to local versus distant recurrences, and between effusion versus solid
      recurrences. Various approaches, including a combination of chemotherapy and BRM,
      therefore, may have to be applied to overcome these drug resistances in practical
      chemotherapies for recurrent tumors.

PMID- 7826169
TI  - [Susceptibility to antimicrobial drugs of strains of bacilli used as a basis for
      various probiotics].
AB  - Five strains of the genus Bacillus used as components of biological preparations
      i.e. bacterin SL, biosporin, bactisubtil and subalin were tested for their
      susceptibility to 38 antimicrobial agents, The strains were simultaneously
      resistant to 5 antibiotics: astreonam, colistin, penicillin, ceftizoxime and
      cefuroxime. High susceptibility of the strains to some penicillins,
      cephalosporins and aminoglycosides was recorded. The gene engineered strain B.
      subtilis 2335(105) marked by the kanamycin resistance gene showed cross
      resistance to amikacin and tobramycin. Trimetoprim, sulfotrimetoprim and
      norfloxacin proved to be active against the strains.

PMID- 7826170
TI  - [Comparative study of the effect of antibiotics on the vital activity of plague
      microbe absorbed by macrophages].
AB  - The influence of aminoglycosides (gentamicin, sisomicin and amikacin),
      cephalosporins (cefotaxime, ceftazidime and cefazolin) and semisynthetic
      penicillins (ampicillin and azlocillin) on the vital activity of macrophage
      absorbed plague microbe was studied in a model of peritoneal macrophages of
      albino mice. It was shown that the aminoglycosides and betalactams added to the
      medium for the cultivation of the macrophages with the absorbed cells of the
      plaque microbe lowered the intensity of the plague microbe multiplication and
      promoted the phagocytosis completion when exposed for a prolonged time (24
      hours). When the influence was body-mediated (albino mice), even a single
      administration of the antibiotics was sufficient to retard the vital activity of
      the macrophage-absorbed plague microbe during the first 6 hours of the
      observation period. It was also shown that the aminoglycosides were more active
      than the betalactams.

PMID- 7826171
TI  - [Analogs of human proinsulin. Obtaining a deletion at the site of the proinsulin
      gene encoding the region of receptor binding].
AB  - A strain producing 5-del-proinsulin was designed on the basis of an industrial
      strain producing human recombinant proinsulin. 5-Del-proinsulin is an analog of
      human recombinant proinsulin. The new strain contains a deletion of 5 amino acid
      residues in the C-end region of the B-chain and a residue of tyrosine at B25. A
      method of oligonucleotide-directed mutagenesis was applied. Comparison of the
      electrophoregrams of the inclusion bodies of the initial and resulting strains
      made it possible to conclude that the pattern of the proteins was the same and
      the electrophoretic mobility of the recombinant proteins was practically
      identical.

PMID- 7826172
TI  - [Virulence of rifampicin and quinolone resistant mutants of strains of plague
      microbe with Fra+ and Fra- phenotypes].
AB  - Experiments with 15 highly virulent antigenically typical strains (Fra+) and 3
      fraction-free strains (Fra-) of the plague microbe were conducted. It was
      demonstrated that a single exposure of the plague microbe to rifampicin or
      nalidixic acid (100 micrograms/ml) resulted in the formation of mutants (Rifr or
      Nalr) resistant to the drugs. The mutation frequency was 10(-10)-10(-8). All the
      Nalr mutants showed cross resistance to ciprofloxacin, a 3rd generation
      quinolone. A comparative study of the virulence of the clones in the population
      of the initial strains of the plague microbe and the cultures of the Rifr and
      Nalr mutants revealed that the predominating majority of the variants resistant
      to rifampicin and the quinolone preserved their high virulence. The resistance
      level of the mutants was sufficient for inducing the infection development in the
      albino mice at the background of the therapy with rifampicin, nalidixic acid or
      ciprofloxacin: no statistically significant differences in the values of the LD50
      of the culture for the treated and nontreated animals were recorded. The Rifr and
      Nalr variants of the fraction-free strains of the plague microbe preserved their
      ability to overcome the specific immunity in the albino mice. The experimental
      data indicated that the rifampicin or quinolone monotherapy required a caution
      and the combined etiotropic therapy was more advantageous since it decreased the
      risk of the complications due to the drug resistant virulent variants of the
      plague microbe forming during the treatment.

PMID- 7826173
TI  - [Use of a new drug, lomefloxacin (maxaquin), from the fluoroquinolone group in
      the treatment of patients with wound infection].
AB  - A clinicolaboratory study on the efficacy of lomefloxacin (maxaquin, Searle, USA)
      was carried out in the treatment of 31 patients with wound infections. In the
      complex therapy the clinical efficacy of the drug amounted to 96.7 per cent and
      its bacteriological activity reached 64.6 per cent. The drug tolerance in the
      majority of the cases was good. Only in one patient an allergic reaction in the
      form of multiple skin eruption on the 6th day of the treatment was recorded. One
      patient showed an insignificant increase in the level of alanine aminotransferase
      not accompanied by any signs of hepatic insufficiency.

PMID- 7826174
TI  - [Pharmacokinetic validation of intra-arterial lymphotropic antibiotic therapy of
      pyo-inflammatory diseases of organs of the peritoneal cavity].
AB  - Intraarterial infusion of antibiotics provided a 1.39-2.84-fold regional increase
      in the antibiotic concentration as compared to that after the intravenous
      infusion in the organs and tissues of the abdominal cavity affected by an
      inflammatory process. Regional intraarterial lymphostimulation provided a 1.31
      1.64-fold increase in the antibiotic resorption from the affected organs and
      tissues of the abdominal cavity to the relevant regional lymph nodes. Combined
      intraarterial administration of the antibiotic and lymphostimulant made it
      possible to provide high antibiotic concentrations in both the affected organs
      and tissues of the abdominal cavity and the respective portions of the regional
      lymphatic system.

PMID- 7826175
TI  - [Mycoses in oncologic patients].
AB  - Lately the frequency of fungal infections in oncological patients considerably
      increased. The cause is a decreased immune status and in particular decreased
      immunity against fungal infections in oncological patients because of the
      oncological disease and aggressive treatment. In the patients treated with
      immunodepressants the frequency of Candida vegetating on the skin and in open
      cavities was higher. Fungi were isolated from the pathological materials of 8.9
      per cent of the patients in 1981, 12 per cent in 1990, 17 per cent in 1991 and 24
      per cent in 1992. Candida were more frequent than other taxa. The frequency of
      Candida amounted to 92-97 per cent of all the fungal isolates. This stipulated
      for the necessity of not only an adequate use of antimycotics in the treatment of
      fungal infections and more often mixed bacterial and fungal infections but also
      the prophylaxis of fungal infections.

PMID- 7826176
TI  - [Antibacterial action of the polymeric antiseptic catapol].
AB  - Activity of a polymer derivative of catamine AB, the antiseptic catapol, against
      gram positive and gram negative bacteria was studied. The effect of catapol on
      structural components of bacterial cells and permeability of bacterial cell
      membranes was investigated. The possibility of varying the susceptibility of
      bacteria to catapol and the effect of catapol on bacteria susceptible to
      antibiotics were evaluated. It was shown that by its in vitro antibacterial
      activity, catapol does not significantly differ from catamine AB.

PMID- 7826177
TI  - [Activity of ethics committees in clinical trials of antibacterial drugs].
AB  - Clinical trials are designed and conducted worldwide in accordance with
      International Rules of Good Clinical Practice (GCP). The guidelines are aimed at
      establishing a system ensuring personal integrity and welfare of trial subjects.
      A significant point of the activity of Ethics Committees in GCP is protection of
      trial subjects. The experience of the local Ethics Committee of the Smolensk
      Medical Institute with protection of clinical trials of antibacterials is
      presented. The importance of setting up Ethics Committees for supervision of
      clinical trials in Russia is emphasized.

PMID- 7826178
TI  - [Cefpiramide--a new cephalosporin antibiotic].

PMID- 7826179
TI  - [Effect of H-ATPase stimulators on cyclosporin biosynthesis].
AB  - An analogy was observed between the mechanisms of action of phytohormones on
      plant cells and cells of the fungus producing cyclosporine. Fusicoccin and
      cytokinin were shown to have a high stimulating action on the biosynthesis of
      cyclosporine. The stimulating concentrations of the phytohormones and the time of
      their maximum effect were determined. The electron microscopic studies
      demonstrated that an increase in the level of the cyclosporine synthesis
      correlated with a significant increase in the number of the cells in the state of
      the coagulation necrosis.

PMID- 7826180
TI  - [Autologous blood transfusion in open heart surgery].

PMID- 7826181
TI  - Protective effect of gabexate mesilate (FOY) against pancreatic injuries induced
      by ethanol in rats.
AB  - Four-hour intravenous ethanol infusion at two doses of 0.5 and 1.0 g/kg.hr caused
      mild, but significant, rises in serum amylase and pancreatic water content as
      well as pancreatic histological changes such as interstitial edema in rats. These
      doses of ethanol also caused an impaired pancreatic adenylate energy charge
      levels and increased pancreatic mitochondrial fragility. The dose of 0.2 g/kg.hr
      caused only marginal changes in these parameters. Moreover, gabexate mesilate
      (FOY) at the dose of 20 mg/kg.hr inhibited almost completely all these pancreatic
      injuries induced by ethanol, exerting significant protective effects. These
      results suggest that impaired pancreatic energy metabolism and increased
      mitochondrial fragility seem to play an important role in the pathogenesis of
      ethanol-induced pancreatic injuries, and that some unknown protease activity,
      which can be inhibited by FOY, also seems to play an important role. Finally, FOY
      seems to be useful in protecting the exocrine pancreas in the alcoholic patients.
      Excessive intake of ethanol often precedes the development of both acute and
      chronic pancreatitis, and pancreatitis occurs more commonly in alcoholics than in
      the general population. Thus, alcohol has been reported to be one etiological
      factor in the pathogenesis of human pancreatitis. However, little is known about
      the mechanism whereby alcohol induces pancreatic acinar cell injuries. Moreover,
      there have been few reports regarding the effect of ethanol on pancreatic
      adenylate energy metabolism. Recently, we have reported the important role of
      subcellular organellar fragility in the triggering of pancreatic injuries in
      other models of pancreatitis such as secretagogue-induced and pancreatic duct
      obstruction. In this study, we evaluated the effect of ethanol administration at
      various doses on the exocrine pancreas from several parameters including
      pancreatic adenylate energy charge levels and subcellular organellar fragility as
      well as the protective effect of a synthetic protease inhibitor, gabexate
      mesilate (FOY) [ethyl-4-(6-guanidino hexanyloxy benzoate) methanesulfonate; M.W.
      417 daltons].

PMID- 7826183
TI  - [Agricultural products handling: methods of feasibility evaluation].
AB  - Post-harvest problems are important constraints to the expansion of production of
      food in many Latin American countries. Besides problems of bulkiness,
      perishability and seasonal production patterns, the necessity of reducing
      transportation costs, increasing rural employment, and finding new markets for
      processed products, requires the development of processing technologies. Possible
      processed products include a vast range of alternatives. Given limited time and
      resources, it is not always feasible to carry out detailed studies. Hence a
      practical, low-cost methodology is needed to evaluate the available options. This
      paper presents a series of methods to evaluate different processing
      possibilities. It describes in detail each method including a rapid initial
      assessment, market and consumer research, farm-oriented research, costs and
      returns analysis and finally, some marketing and promotion strategies.

PMID- 7826182
TI  - The intrabiliary rupture of hydatid cyst of the liver.
AB  - The intrabiliary rupture of hydatid cyst of the liver is a severe and relatively
      frequent complication. In this study six similar cases are presented. 4 of the
      cases had hydatid cyst surgery before the admission. The obstructive jaundice,
      cholangitis and unclosed bile fistula are the most frequent clinical findings.
      Ultrasound is very useful for the diagnosis. In the cases of space occupying
      lesions of the liver with wide choledochus (1.1 cm >) the intrabiliary rupture of
      hydatid cyst can be suspected by ultrasonographic examinations. Surgical therapy
      as the capitonnage combined with the resection of the projecting dome of the cyst
      and T tube application remains a method which gives good results and has low
      mortality and morbidity.

PMID- 7826184
TI  - [Trace elements balance in treated phenylketonuria children. Consequences of
      selenium deficiency on lipid peroxidation].
AB  - We studied Ca and Mg and trace elements (Zn, Cu, Fe, Mn, Se) in 15 P.K.U.
      children treated with strict Phe-reduced diet and in a control group. P.K.U.
      children are significantly lower (p < 0.01) plasma and erythrocyte Se as well as
      significantly lower (p < 0.01) activities of Glutathione-Peroxidase (GSH-Px), a
      seleno-dependent enzyme in erythrocytes and in plasma. Concomitantly with
      defective GSH-Px activities we observe significantly (p < 0.01) increased levels
      of lipid peroxidation products: malonaldialdehyde (MDA) and organic
      hydroperoxides (O.H.P.). So, Se supplementation appears to be necessary in low
      phenylalanine products used in P.K.U. treatment.

PMID- 7826185
TI  - [Exclusion of alpha-linolenic acid from diets for rats during several
      generations. I. Effect on reproduction and postnatal growth].
AB  - The effects of a dietary alphalinolenic acid (18: 3w3) deficiency on reproduction
      and post natal growth in rats during 3 successive generations were studied.
      Female rats received respectively a diet with sunflower oil at 10% (deficient
      diet) or a diet with soya oil at 10% (control diet). The results showed that in
      our experimental conditions deficient diet affects: fecundity, fertility, post
      natal growth and cause a high rates of perinatal mortality from birth to post
      partum day 3: Perinatal mortality increased with successive gestation from 14.6%
      to 18.6% compared with the survival of control. The fatty acid composition of
      placenta phospholipids and milk lipids reflected the nature of the dietary oil.
      The possibility that 18: 3w3 might function in a way different from the EFA role
      of 18: 2w6 in reproduction at least in rats has been discussed.

PMID- 7826186
TI  - [Growth and sex dimorphism in school children according to their father's
      occupation].
AB  - A cross-sectional morphometric study on 569 school children from the city of San
      Clemente del Tuyu (Buenos Aires, Argentina) has been performed. The sample was
      subdivided into 28 subgroups according to the age range (7-13 years old), sex,
      and occupational status -low or high- of the fathers. Body weight, height,
      sitting height, and head and arm circumferences were measured. Statistics of
      analysis of variance (ANOVA) and Tukey test for unequal sample sizes were
      performed at each stage of age. Both males and females belonging to the lower
      social status showed a general decrement in growth: shortening in leg length was
      evident. Since the girls from both occupational status showed -in general terms
      hypothesis of "better canalization of the females" has been corroborated by the
      present work.

PMID- 7826187
TI  - [Growth in school children of Villa IAPI (Quilmes, Buenos Aires, Argentina)].
AB  - Growth in schoolchildren of Villa IAPI--a poor neighborhood placed near Buenos
      Aires (Argentina)--were cross-sectionally studied. Six hundred and forty five-
      291 males and 354 females--children from six to twelve years old were weighed
      (W), and the standing (StH) and sitting (SiH) heights, the head (HC) and the arm
      (AC) circumferences, and the triceps (TS) an the subscapular (SS) skinfolds were
      measured. The muscular braquial circumference (MC), and the length of the
      inferior segment of the body (IS) were also calculated. All of the measurements
      were transformed to "z" scores. It was observed that in all cases--except for 11
      year-old females--both W and StH were diminished. This trend was stronger in
      males than in females. Both SiH an HC did not show differences with respect to
      local growth standards. Skinfold values however, were always greater in Villa
      IAPI children--except SS in 9 to 12 year-old males, and in 12 year-old females-
      than those of normal standards, Such differential growth pattern suggests that
      two joined strategies--for protection and adaption to unbalanced environment-
      actually acted in the Villa IAPI population.

PMID- 7826188
TI  - [Caloric nutritional evaluation of the menu served to the university community of
      the Universidad Nacional de San Luis, Republica Argentina].
AB  - We have analysed the meals for lunch and dinner at the University cafeteria,
      during one Winter week (June through September); in this season the menus are
      repeated every week round. A percentage analysis (humidity, ashes, lipids,
      protein, raw fiber, and nitrogen-free extract) was carried out on the sample,
      which were appropriately processed, thus allowing us to know the nutrients amount
      and caloric value of each meal. When examining both the formulas ingredients and
      the technique applied to the preparation of the meals, it was found that they
      have the best cooking quality, and also that their amount is sufficient (see
      tables). As to the meals nutrients, the results allow us to conclude that the
      diets are hypercaloric as well as hypoproteic, with a preponderance of proteins
      of animal origin.

PMID- 7826189
TI  - Effect of succinylation of oil palm protein concentrates on the functional
      properties.
AB  - Defatted kernel flour of oil palm, grounded to 60 mesh, was taken as raw material
      to produce protein concentrates (70.8%) protein) which were succinylated at
      different levels (0.05; 0.2 and 0.6). The extent of acylation was measured as
      percentage of lysine modification reaching values from 18.4% to 48.6%. Protein
      concentrate functional properties were determined: Water solubility (pH 2-10);
      water absorption (320%); oil absorption (2.2 ml oil/g), emulsion activity and
      emulsion stability (28-46%). The functional properties were enhanced by
      succinylation if compared with the untreated protein concentrate, however, "in
      vitro" digestibility was not affected, by succinylation. In summary, the results
      of this study indicate that acylation using succinyl anhydride can improve the
      functional properties of oil palm protein concentrate over those without such
      treatment.

PMID- 7826190
TI  - [Formulation and evaluation of a beverage based on whole milk and precooked rice
      flour].
AB  - The objective of this research was to formulate and evaluate a beverage based on
      powdered whole milk and precooked rice flour, with good nutritional contribution,
      good acceptability and stability, which permits to be included in the nutritional
      Protection Programs carried out by the National Institute of Nutrition of
      Venezuela. Six different mixtures were prepared and evaluated organoleptically in
      liquid form. The preferred one was submitted to nutritional evaluation, acid
      determination and microbiological analysis during seven months, while samples
      were kept at temperatures of 5 degrees C, 27 degrees C and 37 degrees C. The
      nutritional composition of the selected mixture expressed by 100g was the
      following: kcal 423, proteins 11g, fat 9.1g, niacin 1 mg, thiamine 0.2 mg,
      riboflavin 0.6 mg, calcium 295.8 mg and phosphorous 287.5 mg. The protein quality
      was determined by the Protein Efficiency Ratio (PER) and Net Protein Ratio (NPR)
      was 3.01 +/- 0.2 and 3.74 +/- 0.3 respectively, compared with casein of 3.54 +/-
      0.3. This data showed that the product developed represents from the nutritional
      point of view a good alternative to prevent undernutrition in the country. The
      stability study reported a useful life time of seven months at temperatures of 5
      degrees and 27 degrees C and less than two months at 37 degrees C.

PMID- 7826191
TI  - [Elaboration and evaluation of infant food based on Andean crops].
AB  - The Andes mountain range of South America is one of the most important centres
      for crop domestication, potato, corn, and lesser known grains such as quinua,
      canihua, kiwicha and tarwi are indigenous of these highlands. These Andean grains
      have adapted perfectly to the climatic and geographical conditions present,
      whereas other grains have not been able to survive. In addition to their
      hardiness, they also have a high nutritional value. Bearing in mind on one hand,
      the high nutritional value of these indegenous products, and on the other hand
      the high rate of child malnutrition prevalent in the population, it was
      considered important to look for new variations in their processing which would
      facilitate their consumption by the poor working classes, especially the
      children. Accordingly three different flour mixtures were developed based on
      these Andean grains, the mixtures were then subjected to bromatological and
      biological analysis. The three new flour mixtures were: Quinua-Canihua-Broad Bean
      (Q-C-B), Quinua-Kiwicha-Bean (Q-K-B) and Kiwicha-Rice (K-R). The protein content
      of these mixtures varied between 11.35-15.46 g/100g, the mixture K-R having the
      lowest protein level and the Q-C-B having the highest. The Q-K-B mixture had the
      highest chemical score, PER and NPU value. This PER value of 2.59 was higher than
      the value of casein which was 2.50. In addition this mixture had a chemical score
      of 0.94 and a NPU value of 59.38. The Q-C-B mixture had a chemical score of 0.88
      and its PER, NPU and Digestibility values were 2.36, 47.24 and 79.2
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7826192
TI  - [Peruvian corn of high protein quality. Digestibility and use in malnourished
      children].

PMID- 7826193
TI  - [Growth, somatomedin and nutrition].
AB  - The skeletal growth-promoting action of growth hormone appear to be mediated by
      circulating somatomedins or insulin-like growth factor(s) (IGF), which act
      directly to promote the proliferation of growing cartilage. The actions of IGF(s)
      include also insulin-like activity in extraskeletal tissues and mitogenic
      activity. Serum concentrations of IGF(s) were found to be dependent on hormonal
      levels and nutritional status and are reduced by malnutrition or dietary
      restrictions. The actions of somatomedins may be modulated at the tissue level by
      somatomedins inhibitor, factor that may act to limit growth in conditions of
      hormonal and/or nutrition deficiency. Plasma concentration of somatomedins are a
      good marker of acute directional change in nitrogen balance and dietary energy
      and protein appears to be particularly important for both generation of
      somatomedins, and their action on growing cartilage. Measurement of somatomedin
      concentration shows promise as a means for monitoring the response of
      malnourished children and rats to nutrition repletion.

PMID- 7826194
TI  - Drug membrane interaction and the importance for drug transport, distribution,
      accumulation, efficacy and resistance.
AB  - Some aspects of drug membrane interaction and its influence on drug transport,
      accumulation, efficacy and resistance have been discussed. The interactions
      manifest themselves macroscopically in changes in the physical and thermodynamic
      properties of "pure membranes" or bilayers. As various amounts of foreign
      molecules enter the membrane, in particular the main gel to liquid crystalline
      phase transition can be dramatically changed. This may change permeability, cell
      fusion, cell resistance and may also lead to changes in conformation of the
      embedded receptor proteins. Furthermore, specific interactions with lipids may
      lead to drug accumulation in membranes and thus to much larger concentrations at
      the active site than present in the surrounding water phase. The lipid
      environment may also lead to changes in the preferred conformation of drug
      molecules. These events are directly related to drug efficacy. The determination
      of essential molecular criteria for the interaction could be used to design new
      and more selective therapeutics. This excursion in some aspects of drug membrane
      interaction underlines the importance of lipids and their interaction with drug
      molecules for our understanding of drug action, but this is not really a new
      thought but has been formulated in 1884 by THUDICUM: "Phospholipids are the
      centre, life and chemical soul of all bioplasm whatsoever, that of plants as well
      as of animals".

PMID- 7826196
TI  - Hypoxic radiosensitizers: substituted styryl derivatives.
AB  - A number of novel styryl epoxides, N-substituted-styryl-ethanolamines, N-mono and
      N,N'-bis-(2-hydroxyethyl)-cinnamamides--analogues to the known radiosensitizers
      RSU-1069, pimonidazole and etanidazole--display selective hypoxic
      radiosensitizing activity. The styryl group, especially when substituted by
      electron withdrawing groups, was found to be bioisosteric to the nitroimidazolyl
      functionality. The most active derivative 2-(2'-nitrophenyl)ethen-1-yl-oxirane 8a
      displayed a sensitizer enhancement ratio (SER) of 5 relative to misonidazole.

PMID- 7826195
TI  - [Antimycobacterial acting carbazole derivatives].
AB  - Carbazoles are synthesized and tested for antimycobacterial properties (M.
      tuberculosis H 37 Ra, Middlebrook-7H9-broth). The different antimycobacterial
      properties of diastereomeres are examined using compounds 32 and 33, those of a
      racemic compound and the (+)-enantiomer are tested with (+/-)-12/(+)-12 and (+/-)
      5/(+)-5, respectively. (+)-12 is prepared by enantioselective synthesis.

PMID- 7826197
TI  - [Studies on 1,4-naphthoquinones. 23. 2-3-Halogen-2-3-nitrophenyljuglone
      derivatives, synthesis and cytotoxic properties].
AB  - Radical arylation of 1,4-naphthoquinones is possible by oxidative decarboxylation
      of 2- and 4-nitrobenzoic acid. With 2- and 3-halogenojuglone derivatives the 4
      nitrophenyl compounds 10-13 are prepared in good, the 2-nitrophenyl analogues 14
      17 only in poor yields. All compounds are inactive against the virus types HSV
      and HIV and their marked cytotoxicity in part depends on the substitution
      pattern. The 3-aryl and o-nitro derivatives are more active than their 2-aryl and
      p-nitro analogues and the influence of the chloro or bromo substitution is only
      remarkable in the case of 12/13.

PMID- 7826198
TI  - Bronchodilator activity of theophylline derivatives substituted at the 7
      position.
AB  - Theophylline derivatives with several groups linked at the 7-position were
      synthesized and their pharmacological activities were studied on guinea pig.
      Relaxant action in the tracheal muscle was increased in comparison with that of
      theophylline when the 3(2H)-pyridazinone system was linked to 7-(2-ethyl)
      theophylline through the piperazine ring, but decreased when the 7-(2-ethyl)
      theophylline was linked to 3(2H)-pyridazinone ring through an amino group.

PMID- 7826199
TI  - New NO-donors with antithrombotic and vasodilating activities, VII: Z/E-isomerism
      in thiazole- and 1,3,4-thiadiazole-2-nitrosimines.
AB  - In thiazole- (23 compounds) and 1,3,4-thiadiazole-2-nitrosimines (20 compounds)
      Z/E-isomers were described by 1H-NMR-spectroscopy. There is a mutual conversion
      of the isomers. The coalescence temp. (Tc) mostly is 310 K. In the thiazole
      series, however, for five compounds higher energy barriers are observed. This is
      due to substituents in 4-position with electron withdrawing properties. The Tc is
      increased when the compounds are dissolved in water instead of DMSO. Hereby it is
      concluded that the isomers have Ze or Ee configuration. It is made probable that
      the low field signal for the substituent in 3-position corresponds to the Ze
      isomer, which has a slight preference. The free enthalpy of rotation, calculated
      approximately, is between 56.0 (1m) and 73.7 kJ/mol (1r).

PMID- 7826200
TI  - Synthesis and antiviral evaluation of hydantoin analogues of AZT.
AB  - 3'-Azidonucleosides 4 have been synthesized by condensation of silylated (Z)-5
      ethylidenehydantoin and (Z)-5-benzylidenehydantoin with methyl 3-azido-5-O-tert
      butyldiphenylsilyl-2,3-dideoxy-D-erythro-pento furanoside (3). The nucleosides 4
      were deblocked on treatment with tetrabutylammonium fluoride. The ethylidene
      group isomerized from Z to E configuration during the nucleoside synthesis. The
      new nucleosides did not show any appreciable activities against HIV-1 or HSV-1.

PMID- 7826201
TI  - Alpha 1-adrenoceptor blocking activity of some ring-open analogues of prazosin.
AB  - Synthesis and structural characterization of some ring-open analogues of Prazosin
      containing either the guanidine substructure or urea-equivalent groups are
      described. The opening of the pyrimidine ring in Prazosin is very important as
      far as the affinity for alpha 1-adrenoceptor is concerned. The pA2 values of the
      ring-open derivatives are 10(4)-10(5) fold lower than that of the parent. It is
      probable that the affinity decrease principally reflects a negative influence of
      the conformational factors in the interaction with the alpha 1-receptor. The
      derivative 5 containing the guanidine moiety, charged at physiological pH, is as
      active as the other derivatives containing the uncharged urea-equivalent groups.
      This behaviour indicates, in this class of compounds, the importance of H-bonding
      interactions with the receptor. When in the ring-open models the ethanediamino
      substructure is substituted for the piperazine ring additional decrease in
      activity occurs.

PMID- 7826202
TI  - Synthesis and biological evaluation of some potential antimalarials.
AB  - Malaria chemotherapy has been well reviewed. Malarial parasites gaining
      resistance is the major problem in the treatment of the disease. Some strains are
      resistant not only to chloroquine but also to amodiaquine. Few new drugs are
      available or foreseen for the near future. The principal metabolite of cinchona
      alkaloids appears to be oxidized at C-2. This may result in a loss of activity.
      Pinder and Burger suggested that a trifluoromethyl group will prevent this
      oxidation. So 2-tribromomethyl-6-methoxy-4-(4-hydroxy-3-pyrrolidinomethylanil
      ino)quinoline (1) was synthesized as a potential biocide (Scheme 1).

PMID- 7826203
TI  - Coat protein-mediated resistance in transgenic plants.
AB  - This review describes the proposed mechanism(s) of classical virus cross
      protection in plants, followed by those suggested for coat protein-mediated
      resistance (CP-mediated resistance). Although both have common features, cross
      protection is thought to be a complex response caused by the replication and
      expression of the entire viral genome, whereas the resistance conferred by the
      expression of a virus coat protein gene is more limited. The term genetically
      engineered cross-protection is frequently used because in many cases the
      phenotype of resistance mimics that of cross-protection. However, CP-mediated
      resistance, although a narrow term, more accurately describes the resistance that
      results from the expression of a virus CP gene in transgenic plants.

PMID- 7826204
TI  - A herpes simplex virus type 1 ICP22 deletion mutant is altered for virulence and
      latency in vivo.
AB  - The in vivo function of the herpes simplex virus type 1 immediate early gene
      ICP22 has been investigated in mice and guinea pigs using a deletion mutant
      (del22Z) of HSV-1(F) that lacks all but 18 nucleotides of the ICP22 coding
      sequence. This mutant carries the bacterial lacZ gene at the site of the deletion
      and makes functional beta-galactosidase, but is unable to synthesize any
      detectable ICP22 messenger RNA or protein in vitro. Del22Z was impaired in its
      ability to cause death in mice following intracerebral, intraperitoneal, or
      intravaginal inoculation. The mutant failed to produce lesions or other visible
      signs of infection after bilateral corneal infection of mice but could be
      recovered from trigeminal ganglia explanted at day 30 after inoculation. Del22Z
      replicated poorly after intravaginal inoculation of mice and guinea pigs in
      comparison to the parental virus, and was not recoverable from the dorsal root
      ganglia of either species. Nevertheless, del22Z sequences could be detected in
      the dorsal root ganglia of guinea pigs at day 30 by the polymerase chain
      reaction. These studies demonstrate that the ICP22 gene product is required for
      acute infection and virulence in two standard in vivo animal models.

PMID- 7826205
TI  - Biochemical and genomic characterization of muscovy duck parvovirus.
AB  - A duck parvovirus (DPV) isolated from muscovy ducks during the epizootic in
      France in 1989 was purified from inoculated allanto-amniotic fluids by CsCl
      density gradient centrifugation and characterized. Full and empty non-enveloped
      icosahedral viral particles were observed banding at densities of 1.39 to 1.42
      and 1.38 respectively, with a diameter of 22 to 23 nm. Viral proteins were
      analyzed by SDS-PAGE and the estimated molecular weights of the 3 major proteins
      were 91, 78 and 58 kDa. The nucleic acid was shown to be a single-stranded DNA of
      about 5,300 bases with terminal palindromic hairpins. These results confirm the
      previous classification of the virus in the family Parvoviridae established by
      Jestin et al. [14] on morphological and serological bases. The DPV DNA was
      reannealed indicating that complementary DNA strands were encapsidated. A partial
      restriction endonuclease map was also established. This work constitutes the
      first biochemical and genomic description of a muscovy duck parvovirus.

PMID- 7826206
TI  - Spatial association of HIV-1 tat protein and the nucleolar transport protein B23
      in stably transfected Jurkat T-cells.
AB  - The human immunodeficiency virus (HIV-1) encodes a transactivator protein, the
      product of the tat gene (tat), which is essential for virus replication. In this
      study, immunogold electron microscopy was used in a stably transfected Jurkat T
      cell line that constitutively expresses HIV-1 tat protein to determine the
      subcellular and intranuclear distribution of tat protein. Two nucleocytoplasmic
      shuttle proteins C23/nucleolin and B23 and a third nucleolar antigen that was
      detected by monoclonal antibody MAb 1277 were also examined. In addition, spatial
      association of C23 and B23 with tat protein at several subcellular locations was
      examined in dual-labeling experiments. The results showed that tat protein was
      found in both the cytoplasm and nucleus but was especially prominent within the
      dense fibrillar and granular components of the nucleolus. There was little
      labeling of tat protein in the fibrillar centers where MAb 1277 antigen was
      localized at a comparatively high level. The subcellular and intranucleolar
      distribution of tat protein was virtually identical to the pattern seen with C23
      and B23. Although the intranuclear distributions of C23, B23 and tat protein were
      very similar, C23 and tat protein were seldom spatially associated. In contrast,
      B23 and tat protein were frequently spatially associated in the nucleolus and in
      several other subcellular locations including the cytoplasm, nucleoplasm, at the
      nuclear envelope and plasma membrane. While a physical association was not
      directly demonstrated in this study, the spatial association between B23 and tat
      protein strongly suggest that such an association may exist.

PMID- 7826207
TI  - Analysis of long-term viral expression in CEM cells persistently infected with
      non syncytium-inducing HIV-1 strains.
AB  - CEM cells were infected with three HIV-1 non syncytium-inducing (NSI) strains
      obtained from AIDS patients or seropositive individuals. The surviving cells were
      followed for several months in the persistently infected cultures designated
      65870/CEM, 65871/CEM and 3929/CEM, and analyzed for virus expression using light
      and electron microscopy, immunofluorescence, reverse transcriptase assay,
      polymerase chain reaction amplification (PCR), nucleic acid hybridization and
      flow cytometry. The virus isolates induced relatively few syncytia and other
      cytopathic effects in the corresponding cell lines and the number of cells
      positive for virus expression never rose above 44%. Distinct peaks of antigen
      positive cells were obtained, coincident with high levels of reverse
      transcriptase activity. The cultures were strongly resistant to superinfection by
      laboratory strain Lai, with the exception of 65870/CEM which expressed HIV
      antigens in up to 15% of the cells for a few days. However, cell lysis was
      minimal in all cases. After long-term cultivation of the three cultures, no
      antigen-positive cells were detected and no trace of virus expression could be
      observed. The remaining cells consisted entirely of CD4-negative cells. PCR
      analyses indicated that cells harboring a provirus were progressively eliminated
      from the cultures, leaving only virus-free cells. In this system, cells carrying
      a latent provirus survive for a limited period of time before virus activation
      induces cell lysis. These results suggest that at least three types of cells
      exist in the CEM cell line: CD4-positive cells which are rapidly killed by the
      virus, a second type harboring a latent viral genome after the infection and
      which grow normally until activation of the resident genome by external or
      internal signal(s), and a third type which represents rare CD4-negative cells
      present in the initial CEM population and which are selected for by the NSI
      isolates. This is the first study documenting specific interactions between NSI
      strains of HIV-1 and distinct subpopulations of CEM cells grown as a single cell
      culture.

PMID- 7826208
TI  - Application of a transformed cell line constitutively expressing HSV-1
      polypeptides for the detection of HSV antibodies in human sera by an enzyme
      immunoassay.
AB  - We have previously reported the construction of a cell line BA4, constitutively
      producing the glycoproteins gD, gG, and alpha 4, the major regulatory protein of
      HSV-1. These cells have been selected in stepwise increasing concentrations of
      methotrexate and shown to produce much higher amounts of gD than non-selected
      cells. Extracts of the selected cells were used in an enzyme linked immunosorbent
      assay to detect HSV antibodies in human sera obtained from Greek blood donors. We
      report here that (i) the assay developed is able to distinguish HSV antibody
      positive from negative human sera and (ii) that its application in an
      epidemiological survey showed that the incidence of HSV infection in the general
      population in Greece is 90.4%.

PMID- 7826209
TI  - Biological and pharmacokinetic properties of a novel immunoglobulin-CD4 fusion
      protein.
AB  - We report a CD4-immunoglobulin fusion protein in which the first two
      extracellular domains of human CD4 replace the Fc region of the immunoglobulin.
      When co-expressed with a gene encoding an immunoglobulin light chain, the protein
      was covalently assembled into a form having an M(r) consistent with that expected
      for two fusion heavy chains and two immunoglobulin light chains. The antigen
      specificity of the antibody was retained, however, binding to HIV gp120 was lost.
      Pharmacokinetic analysis revealed the in vivo half-life of the fusion protein to
      be 2.4 h in mice.

PMID- 7826211
TI  - Characterization of a G14 equine rotavirus (strain CH3) isolated in Japan.
AB  - Antigenic and genomic properties of equine rotavirus strain CH3 isolated in Japan
      were studied by cross-neutralization tests and nucleotide sequence determination
      of the VP4 and VP7 genes. It was shown that the strain CH3 belongs to G14 and
      shares VP4 genotype with strain H2.

PMID- 7826210
TI  - Protective efficacy in mice of a secreted form of recombinant dengue-2 virus
      envelope protein produced in baculovirus infected insect cells.
AB  - We constructed a recombinant baculovirus encoding a dengue (DEN)-2 virus envelope
      glycoprotein truncated of 102 amino acids (aa) at its C-terminus (D2E delta 102).
      The production, processing and transportation of the recombinant protein in
      baculovirus-infected Spodoptera frugiperda (Sf9) cells and its immunogenic
      properties in mice were compared to those of a previously characterized
      recombinant DEN-2 E-protein with a 71aa C-terminal truncation (D2E delta 71).
      Both proteins were transported through the Golgi complex and their N
      oligosaccharides of the high mannose type were processed to the complex mannose
      type. D2E delta 102 transited to the plasma membrane and was secreted whereas D2E
      delta 71 presumably remained associated with the plasma membrane. The
      reactivities of the recombinant proteins with neutralizing monoclonal antibodies
      were similar. Both intracellular and extracellular D2E delta 102 induced
      neutralizing antibodies in mice and were thus immunogenic. The level of
      protective immunity to DEN-2 virus encephalitis challenge in mice vaccinated with
      intracellular D2E delta 102 (80%, p < 0.01) was lower than that induced with D2E
      delta 71 (90%, P < 0.001). Sixty-eight percent (P < 0.001) of mice vaccinated
      with 5 micrograms of extracellular D2E delta 102 protein were protected against
      lethal challenge.

PMID- 7826213
TI  - Taxonomy and classification of legume-infecting potyviruses. A proposal from the
      Potyviridae Study Group of the Plant Virus Subcommittee of ICTV.

PMID- 7826212
TI  - The nucleoprotein of Pichinde virus expressed by a vaccinia-Pichinde virus
      recombinant partially protects hamsters from lethal virus challenge.
AB  - Syrian hamsters, strain MHA/Lak, are susceptible to intraperitoneal infection
      with Pichinde virus and die from an overwhelming viremia. We have studied the
      ability of a vaccinia-Pichinde recombinant virus expressing amino acids 51-561 of
      the viral nucleoprotein (VVNP51-561) to protect from lethal Pichinde virus
      infection. Priming with VVNP51-561 significantly delayed mortality and increased
      final survival outcome after challenge with 2 x 10(3) pfu of Pichinde virus. This
      protection was not complete compared to priming with Pichinde virus in the
      footpad, which was not lethal and provided 100% protection. At a higher challenge
      dose of Pichinde virus, 2 x 10(4) pfu, immunization with VVNP51-561 delayed
      mortality but did not increase final survival. The partial protection correlated
      with an early but not late reduction in infectious virus in serum, kidney and
      liver, and infectious centers in the spleen. Thus the immune response generated
      by VVNP51-561 could initially control the infection, effectively reducing the
      virus inoculum. As the infection proceeded, virus replication could not be
      limited resulting in death in some hamsters. The partial protection did not
      appear to be mediated by anti-viral antibodies since these were not detected in
      the serum of VVNP56-561-immunized hamsters. This finding appears to support the
      hypothesis that in many arenavirus infections cellular immunity is central to
      viral clearance and protection from reinfection.

PMID- 7826214
TI  - In memoriam Helio Gelli Pereira (1918-1994).

PMID- 7826215
TI  - A phylogenetic and evolutionary justification for three genera of Geminiviridae.
AB  - Gene-by-gene phylogenetic analyses of all of the viruses for which sequences are
      known, as well as analysis of the coding capacities, clearly demonstrated that
      there are two major groups of viruses in the taxonomic family Geminiviridae.
      These are of the Subgroup I type, with one genomic component, which mainly infect
      monocots and are leafhopper-transmitted; and of the Subgroup III type, with one
      or two genomic components, which infect dicots and are whitefly-transmitted. The
      existence of "New World" and "Old World" clusters of Subgroup III viruses was
      confirmed, as well as the possession by the latter of an AV1 ORF not present in
      New World viruses. A third minor generic group is defined by viruses of the
      Subgroup II type, which have a single genomic component, infect dicots, and are
      leafhopper-transmitted. The latter group appear to be the result of an ancient
      recombination event between a Subgroup III-like and a Subgroup I-like virus. The
      question of whether one- and two-component Subgroup III viruses should be in the
      same taxon appears hard to resolve: the only distinguishing feature of the one
      component Subgroup III viruses is that they apparently have no second component,
      as gene-for-gene comparisons of the "A" components of the viruses with other
      Subgroup III viruses place them within a larger Old World group of viruses, most
      of which are two component. The possibility exists that these viruses may either
      have independently lost their B components, or possess a B component that has
      simply not yet been found. Possible nomenclatural changes to accommodate viruses
      with the same name which are not closely related to one another, and possible
      evolutionary scenarios to account for the observed familial, generic and specific
      diversity of geminiviruses, are discussed.

PMID- 7826216
TI  - Detection of DNA and E7 transcripts of human papillomavirus types 16, 18, 31 and
      33, TGF beta and GM-CSF transcripts in cervical cancers and precancers.
AB  - The association of human papillomavirus (HPV) with a high proportion of cervical
      cancers should allow the efficiency of cytological screening methods to be
      improved. We report here that quantitative detection of HPV types 16, 18, 31 and
      33 DNA and the corresponding E7 transcripts by polymerase chain reaction (PCR)
      may be of value in identifying precancers and cancers. In clinical specimens with
      major cervical lesions, the level of E7 transcription does not appear to be
      related to concomitant transcription of either transformation growth factor-beta
      (TGF beta) or granulocyte-macrophage colony stimulating factor (GM-CSF) genes.

PMID- 7826217
TI  - Phosphorothioate oligonucleotides inhibit the replication of lentiviruses and
      type D retroviruses, but not that of type C retroviruses.
AB  - Phosphorothioate analogs of oligodeoxynucleotides at a concentration of 2 microM
      protected Himalayan tahr cells from infection by caprine arthritis encephalitis
      virus (CAEV) and equine dermis cells from infection by equine infectious anemia
      virus (EIAV). The characteristics of this inhibition against these lentiviruses
      are similar to those previously described for the inhibition of HIV-1 in ATH8
      cells [17]. Thus, the 28-mer homo-oligomer of cytidine [S-(dC)28] was at least as
      effective as three anti-sense sequences targeted to the LTR, gag, and env regions
      of CAEV. The effectiveness of homo-oligomers of equal length was in the order C
      >> A > T, and a random 28-copolymer with a composition of 2C:1G was as effective
      as S-(dC)28. Shorter oligonucleotides were less effective (28 > 14 > 5 mers) for
      all base compositions tested. While replication of a simian type D retrovirus was
      inhibited by S-(dC)28, this compound did not inhibit the cytopathogenicity of two
      type C retroviruses, amphotropic murine leukemia virus (MuLV), and baboon
      endogenous virus, when they were tested in the same cell lines used to support
      the replication of lentiviruses. Southern blot analysis of the high molecular
      weight DNA of drug-treated CAEV-infected cells showed that S-(dC)28 was acting at
      or before the reverse transcription step. Our present data and the earlier
      finding that S-(dC)28 is a potent in vitro inhibitor of the MuLV reverse
      transcriptase [15] suggest that S-(dC)28 is acting very early in the replication
      cycle of these lentiviruses. Since MuLV reverse transcriptase is inhibited in
      vitro, but its replication is not blocked in permissive cells, our data suggest
      that the phosphorothioate oligonucleotides are preventing virus attachment.

PMID- 7826218
TI  - [Interleukin 5 and allergy].

PMID- 7826219
TI  - [A study of hyperreactivity test thresholds over the last 9 years in asthmatics].
AB  - We have regularly performed acetylcholine hyperreactivity tests (Ach-HRT) on
      asthmatics on their first visit to our allergy clinic, and gained the impression
      that Ach-HRT thresholds have risen over the last nine years. We studied the
      thresholds in four different years: 1983, '85, '87 and '91 in 578 male cases and
      680 female cases. Our findings were as follows. 1) The Ach-HRT threshold
      increased in the last 9 years, especially in the asthmatic group aged from 20 to
      59 years old. 2) We studied the factors which might affect Ach-HRT in this age
      group. No significant difference were seen in the percent of peripheral blood
      eosinophil count and in clinical severities. The mean percent of baseline FEV1.0
      was high in '91 and low in '83. We studied the Ach-HRT threshold in case with
      good pulmonary function whose %FEV1.0 was over 90% and found that the Ach-HRT
      threshold was high in '91 and low in '83. 3) The number of extrinsic cases
      increased gradually in number over the 9 years, and a high Ach-HRT threshold was
      clearer in the extrinsic cases. We concluded that the mean Ach-HRT threshold of
      our patients was rising especially in the extrinsic cases.

PMID- 7826220
TI  - [Clinical significance of cat allergens in adult asthmatics--a study of
      inhalation provocation tests].
AB  - We performed a bronchial provocation tests on 40 adult cat sensitive asthmatics
      to study the clinical significance of cat allergens. Immediate asthmatic
      responses (IAR) and/or late asthmatic responses (LAR) were provoked in 29 out of
      the 40 cases. IAR alone was provoked in 12 cases (30%), LAR alone in 7 cases
      (17.5%), dual asthmatic responses (DAR) in 10 cases (25%), and no asthmatic
      response in 11 cases (27.5%). There was no statistical significance in the
      following parameters among the groups: age, baseline of FEV1.0% and of %MMF, RAST
      score to cat epithelium and log value of PC20 in acetyl-choline airway
      hyperreactivity tests. The frequency in contact history with cat was lower in LAR
      alone (14%) than in the other two groups (78% in DAR, 70% in no asthmatic
      response). High RAST scores and low PC20 values were more frequent in DAR than in
      the other groups. Asthmatic responses were found in 15 out of 22 cases (68.2%)
      with a cat contact history and in 10 out of 16 cases (62.5%) without a contact
      history. These prevalence rates were the same. We concluded that cat allergens
      were an important factor not only for child asthmatics but also for adult
      asthmatics.

PMID- 7826221
TI  - [Diagnosis of sinusitis in children with allergic diseases--comparison of waters
      projection radiographs and CT scans].
AB  - Sinusitis is common in children with allergic diseases, and the relationship
      between sinusitis and reactive airway diseases involving asthma has been
      reported. Most pediatricians and physicians base their diagnosis of sinusitis on
      findings from plain radiographs of the sinuses, especially Waters projection
      radiographs. We compared the diagnoses made by 11 pediatric allergists using 56
      Waters projection radiographs with transverse CT findings. The ratio for the two
      diagnosis being consistent (normal plain radiographic findings and normal CT
      findings, or abnormal plain radiographic findings and abnormal CT findings) was
      approximately 60%. Sinusitis in children is often misdiagnosed on the basis of
      findings from Waters projection radiographs alone. Therefore, the use of CT
      findings for the diagnosis of sinusitis together with Waters projection
      radiographs is recommended.

PMID- 7826222
TI  - [Effect of combination therapy with disodium cromoglycate (DSCG) and Ozagrel on
      non-atopic asthmatics].
AB  - Ozagrel (OKY-046), a selective inhibitor of thromboxane biosynthesis has been
      reported to reduce airway hyperresponsiveness in asthmatics. DSCG has been widely
      used for atopic, but not for non-atopic asthmatics. We evaluated the additive
      effect of combination therapy with DSCG and Ozagrel on nonatopic asthmatics.
      Fourteen asthmatics were divided into two groups. The patients in the O-D group
      were initially treated with Ozagrel (400 mg/day) for 4 weeks, and then DSCG (8
      mg/day) was added for another 4 weeks. The patients in D-O group were initially
      treated with DSCG (8 mg/day), and then Ozagrel (400 mg/day) was added for 4 more
      weeks. TXB2, PGF2 alpha, PGE2, 6-keto-PGF1 alpha in sputum and 11-dehydro TXB2 in
      urine were measured before and after 4th and 8th weeks of therapy. Ozagrel
      decreased the metabolites of thromboxane and PGF2 alpha in sputum and urine. PGE2
      in sputum tended to be increased by Ozagrel. DSCG did not affect mediators in
      sputum. Combination therapy with Ozagrel and DSCG showed the additive effect to
      single use on attack score and PF in non-atopic asthmatics.

PMID- 7826223
TI  - [A study on subpopulation of helper T cells in chronic inflammatory demyelinating
      polyneuropathy].
AB  - Chronic inflammatory demyelinating polyneuropathy (CIDP) is thought to be an
      inflammatory autoimmune disease against peripheral myelin. Recently several
      animal models have suggested that preferential activation of Th1 cell response is
      central to the pathogenesis of this disease. We studied the function of CD4
      positive T cell subsets, Th1 cells and Th2 cells by analyzing their
      representative secreting cytokines. Th1 cells secrete Interferon gamma (IFH
      gamma) and Th2 cells secrete Interleukin 4 (IL4). Using enzyme linked immunospot
      (ELISPOT) assay, a very sensitive single cell analysis system, we enumerated IFN
      gamma and IL4 secreting peripheral blood lymphocytes in patients with CIDP. Also
      we examined these cytokines in supernatants of cultured peripheral blood
      lymphocytes by a very sensitive enzyme linked immunosorbent assay (ELISA),
      Immunodot assay and westernblot assay. In culture supernatants of CIDP patients'
      peripheral blood lymphocytes, the levels of both IFN gamma and IL4 were higher
      during the exacerbation stage than the remission stage. In the remission period,
      though the levels of IFN gamma and IL4 were low in the supernatants, the ELISPOT
      assay revealed that the number of IL4 secreting cells was elevated compared with
      that of IFN gamma secreting cells. Our results suggest that the switch from Th1
      to Th2 might play an important role in inducing the remission stage in patients
      with CIDP.

PMID- 7826224
TI  - [A case of bronchial asthma induced by inhalation of dibekacin sulfate].

PMID- 7826225
TI  - [A case of allergic drug-induced hepatitis suspected with rifampicin-induced
      antinuclear antibody].

PMID- 7826226
TI  - [Nuclear cardiology. Indications for its use].

PMID- 7826227
TI  - [Risk factors for cardiovascular diseases in physicians. Preliminary data from
      the VIDAM Project of the Paulista Medical Association].
AB  - PURPOSE: To evaluate the frequency and other characteristics of some
      cardiovascular risk factors among physicians of Sao Paulo State, Brazil. METHODS:
      From a questionnaire, 1395 voluntary physicians answered questions about personal
      and familial cardiovascular disease and risk factors, and blood pressure, serum
      total cholesterol, glucose, height and weight were recorded. RESULTS: The
      frequency of familial history of ischemic heart disease was 24.4%; positive
      personal antecedent of hypercholesterolemia, 12.4%; serum total cholesterol > or
      = 240 mg/dl, 14.3%; positive personal antecedent of hypertension, 8.4%; systolic
      blood pressure > or = 140 mmHg or diastolic > or = 90 mmHg, 23.8%; current
      cigarette smokers, 17.4%; prior cigarette smokers, 19.1%; positive personal
      antecedent of diabetes, 0.8%; serum glucose > 120 mg%, 7.7%; sedentarism, 37%,
      and obesity, 17.2%. CONCLUSION: Cigarette smoking was the only risk factor that
      was taken in account with emphasis by the physicians of Sao Paulo State in order
      to prevent themselves from cardiovascular disease.

PMID- 7826228
TI  - [The electrocardiogram of high resolution during ventricular tachycardia].
AB  - PURPOSE: To evaluate by the signal averaged-ECG (SAECG) the initial portion of
      the activation of the sustained ventricular tachycardia (SVT) and monomorphic
      repetitive ventricular tachycardia (MRVT), correlating the findings with those
      obtained during sinus rhythm (SR). METHODS: Ten patients was studied; five with
      SVT and five with MRVT. Patients with SVT presented a positive SAECG while
      patients with MRVT the test was negative, during SR. The findings of this two
      populations were compared with those obtained in a group of ten patients with
      advanced bundle branch block (ABBB: five RBBB and five LBBB). We analyzed in the
      vector-magnitude obtained during VT and ABBB, the root mean square of the initial
      40 ms portion of the activation (RMS40) and the duration of the low amplitude
      signals < 40 microV from the beginning of the filtered QRS (LAS). To define the
      positiveness of the test in SR, we analyzed the final RMS40 (normal > 20 microV),
      the duration of the LAS < 40 microV at the end of the activation (normal < 38 ms)
      and the total QRS duration (QRSD-normal < 114 ms). RESULTS: (mean)-SVT in SR:
      RMS40 = 11.2 +/- 6.2 microV; LAS = 47.4 +/- 5.8 ms; QRSD = 131.2 +/- 8.7 ms. SVT
      during VT: RMS40 = 6.9 +/- 4.5 microV; LAS = 54.5 +/- 9.1 ms. RMVT in SR: RMS40 =
      59.7 +/- 49.0 microV; LAS = 28.3 +/- 8.5 ms; QRSD = 93.1 +/- 13.0 ms. MRVT during
      VT: RMS = 25.2 +/- 8.8 microV; LAS = 28.9 +/- 11.1 ms. RBBB: RMS = 53.3 +/- 34.2
      microV; LAS = 22.6 +/- 9.8 ms. LBBB: RMS = 54.7 +/- 37.3 microV; LAS = 11.4 +/-
      4.6 ms. The comparison between the data from SVT and MRVT/ABBB showed p < 0.01.
      CONCLUSION: In the studied population, the SAECG was able to identify abnormal
      LAS initiating SVT, that were not present in MRVT and ABBB. This signals probably
      represents intra-myocardial slow conduction, as a portion of a re-entry circuit.
      There was an excellent correlation between the findings during SVT and MRVT with
      those obtained in SR.

PMID- 7826229
TI  - [Pravastatin effects on lipoproteins, Lp (a), apo B and apo A-1 in patients with
      primary hypercholesterolemia].
AB  - PURPOSE: To evaluate the effects of pravastatin on lipoproteins, Lp (a), apo B
      and apo A-I and its tolerability in primary hypercholesterolemic patients in our
      outpatient lipid clinic. METHODS: Twenty-two primary hypercholesterolemic
      patients were evaluated. They had all been treated previously with other
      hypocholesterolemic drugs, including the statins, forming a specific and
      homogeneous group with hypercholesterolemia and definite coronary risk. After 7
      weeks with American Heart Association phase I diet and placebo drug, pravastatin
      was administered during 12 weeks. All patients received an initial daily dose of
      10 mg for six weeks. After this period, this dose was increased to 20 mg. The
      levels of cholesterol, triglycerides, high-density lipoprotein, lipoprotein (a)
      and apolipoproteins A-1 and B were determined. RESULTS: No changes occurred with
      diet and placebo, but pravastatin at a daily dose of 10 mg, reduced significantly
      cholesterol level (7.22%), LDL-cholesterol (13.08%) and increased HDL-cholesterol
      (7.81%). The results were better with 20 mg, achieving a reduction of (28.21%) in
      cholesterol, (36.88%) in LDL-cholesterol, (17.06%) in apo B level and an increase
      of (10.06%) in HDL-cholesterol. The smaller effect observed with the more
      commonly used dosage (10 mg/day) was most probably due to the characteristics of
      the sample with already established hypercholesterolemia, being thus dependent of
      higher concentrations of medications, as observed in previous treatments in our
      outpatient clinic. Side affects with this drug were rare. No biochemical changes
      were observed that would interrupt the continuation of therapy. CONCLUSION:
      Pravastatin was well tolerated and promoted favorable changes in the total
      cholesterol, LDL, apo B and cholesterol/HDL and LDL/HDL ratios of primary
      hypercholesterolemic patients.

PMID- 7826230
TI  - [Study of the autonomic behavior of escape rhythms in congenital atrioventricular
      block].
AB  - PURPOSE: To study the autonomic behavior of the escape rhythm in congenital
      complete heart block (CCHB), using heart rate variability (HRV). METHODS: A group
      of 10 asymptomatic patients with CCHB and narrow QRS was studied, 7 females; mean
      age = 14 +/- 9 years. The following time domain indexes were analyzed from a 24
      hour Holter monitoring. The mean of all RR intervals (NN); the standard deviation
      of the mean (CLV5); the mean of all standard deviations (SDNN); the percent of
      successive differences longer than 50 ms (pNN50); the shortest cycle (CC) and the
      longest cycle (CL). The results were compared with a control group, using the
      Wilcox test for statistical analysis. RESULTS: The results were: NN = 1016 +/-
      276 ms in CHB and 725 +/- 121 ms in control (p < 0.01); CLV5 = 184 +/- 97 ms in
      CHB and 125 +/- 38 ms in control (p = NS); SDNN = 102 +/- 32 ms in CHB and 88 +/-
      29 ms in control (p = NS); rMSSD = 113 +/- 69 ms in CHB and 78 +/- 28 ms in
      control (p = NS); pNN50 = 43 +/- 26% in CHB and 33 +/- 12% in control (p = NS);
      CC = 582 +/- 129 ms in CHB and 333 +/- 49 ms in control (p = 0.05). CONCLUSION:
      No statistical difference was noted by comparing HRV indexes in CHB with control
      subjects, showing that the autonomic behavior of the escape rhythm in CCHB is
      similar to the sinus node in asymptomatic patients. The differences in NN, CC and
      CL are probably related to intrinsic properties of each command.

PMID- 7826231
TI  - [Infectious endocarditis. Analysis of 20 death cases in Santa Casa de Sao Paulo].
AB  - PURPOSE: To analyze the clinical, laboratory and pathological aspects of 20 cases
      of infectious endocarditis (IE) who died. The authors compared patients with
      diagnosis before death of IE and those with diagnosis was made after autopsy.
      METHODS: Twenty patients who died with IE between April 1982 and November 1991
      were studied. We looked for the clinical aspects (fever, cardiac murmurs, anemia,
      splenomegaly, embolic events and skin manifestation), laboratory aspects
      (hemocultures), echocardiographic and anatomopathologic features (valvar
      vegetations events and embolic accidents founded at autopsy). The sample was
      divided in two sub-groups: A--with clinical diagnosis of IE before and B--without
      diagnosis before death. RESULTS: Group A--9 patients aged 8-58 years, 3 men, all
      them with cardiac murmurs, fever and anemia, 5 with splenomegaly. Hemocultures
      were done in 7 patients and positive in 1. Echocardiogram with valvar vegetation
      were found in 4 out of 5 patients (80% positive). At autopsy mitral valve
      vegetation were present in 7, aortic 3, tricuspid 3. One patient showed the
      exposure of three valves and two of 2 valves. Embolic events were found in 4.
      Group B--11 patients most of them older then 50 years (54.5%) (p < 0.05) 5 men,
      all them presented fever and anemia. Cardiac murmurs in 6 (54%) and none with
      splenomegaly. In one case hemoculture and echocardiogram, were done and were
      negative. Anatopathologic study showed compromise of mitral valve in 5, aortic 4,
      tricuspid 2, pulmonary 1. Two patients had 2 valves compromised. In one case a
      mural vegetation (right atrium) was found. Embolic events were present in 2
      cases. CONCLUSION: In group B a significant number of patients (p < 0.05) were
      older than 50 years and presented his symptoms as an acute illness. We concluded
      that older patients with compromised general state and fever with or without
      embolic events IE must be remember.

PMID- 7826232
TI  - [Cardiac involvement in systemic lupus erythematosus. An echocardiographic
      evaluation].
AB  - PURPOSE: To study, by a non-invasive method, patients with systemic lupus
      erythematosus (SLE), to evaluate possible cardiac involvement. METHODS: A hundred
      eight lupic patients, 60 of them during activity, were studied, independently of
      cardiovascular signs and symptoms, by M-mode and two-D echocardiography and
      Doppler. Among the patients in the acute phase, 19 had never used steroid therapy
      before. RESULTS: Echocardiographic evaluation showed cardiac involvement in all
      patients who were in clinical activity. Seven had myocardial involvement with
      systolic impairment. In 35 patients, pericardial effusion was found, all in the
      acute phase. Regarding endocardial involvement, there were valve thickening in 54
      patients in group I (acute phase), valve vegetations in eight and one with mitral
      valve prolapse. There were only six with valve thickening in group II
      (remission). Pulmonary hypertension was observed in 15 patients in the activity
      group and in two during remission. CONCLUSION: Echocardiogram has showed how
      frequent cardiac involvement is in SLE, especially during disease activity and
      being independent of previous steroid therapy. As it is a non-invasive method, it
      could be used in a routine protocol in the evaluation and follow-up of these
      patients.

PMID- 7826233
TI  - [Race and left ventricle hypertrophy without hypertension and pulmonary heart
      disease].
AB  - PURPOSE: To analyze the association between black people and left ventricular
      hypertrophy (LVH) in the absence of hypertension and/or other cardiopulmonar
      disease. METHODS: Data were collected from necropsies carried out in the
      Anatomopathologic Service (APS). Hospital Edgard Santos from 1970 to 1986,
      Salvador. It were included only subjects at ages > or = 20 years and free of
      hypertension and any cardiopulmonar disease. A LV wall > 1.6cm was considered as
      LVH (standardized criteria of the APS). Controls variables were age, sex, and
      absence of the mentioned diseases. It was used a case-control epidemiological
      study design and the association measured by "odds ratio" (OR) for no matched
      case-control study. RESULTS: From the 208 subjects studied, 48 (23.1%) had LVH.
      There was no difference in the frequency of right ventricular hypertrophy between
      cases and controls (p > 0.05). The mean of heart weight was higher for LVH cases
      (p < 0.001), but there was no evidence of association between blacks and LVH (OR
      = 1.05, p > 0.05 and confidence interval at 95% = 0.8, 1.31. The highest odds
      possible for the association in this study (assuming that all 3 LVH losses were
      black subjects) would be 1.5, also no statistically significant. CONCLUSION: In
      the absence of hypertension and other cardiopulmonar diseases, LHV is common in
      necropsies in Salvador, Brazil, with similar frequencies in blacks, whites and
      mullatos and seems not be a risk factor for hypertension in black people.

PMID- 7826235
TI  - [Mitral valve prolapse and cusp elasticity].
AB  - PURPOSE: To verify if systolic bulging of floppy mitral cusps can to elastic
      behavior of their myxomatous collagen tissue. METHODS: Five hearts with floppy
      mitral valves obtained from autopsies were distended with air (20 to 250 mmHg)
      through a catheter connected to the left ventricle. It was observed if some area
      of the atrial surface of the coapted cusps showed variable bulging according to
      the variation of air injection pressures. Molding of those surfaces (gypsum)
      allowed the same kind of analysis by other four researches. It was analyzed the
      cut surfaces of these radially sectioned molds. Lately, isolated tendinae chords
      were submitted to repeated tractions and observed if they exhibited elastic
      behavior. Histological study defined the presence of collagen myxomatous
      degeneration and quantified the amount of elastic tissue. RESULTS: In no case it
      was detected elastic bulding of mitral cusps. Cut surfaces of the molds confirmed
      that no increment of the prominent areas occurred, even in those regions with
      extensive, histologically confirmed, myxomatous substitution of the native
      collagen tissue. CONCLUSION: Increment of the degree of mitral bulging occurring
      during ventricular systole can not be ascertained to cusp elasticity but probably
      to papilar muscle traction.

PMID- 7826234
TI  - [Percutaneous angioplasty and surgical revascularization in renovascular
      hypertension: experience in treatment and long-term follow up in 124 patients].
AB  - PURPOSE: To report the experience in the treatment and long-term follow-up of
      patients with renovascular hypertension submitted to angioplasty and/or surgical
      revascularization, and to compare blood pressure and renal function responses to
      both treatment. METHODS: One hundred and twenty-four patients diagnosed with
      renovascular hypertension, divided, according to the etiology, as atherosclerosis
      (76 patients), fibromuscular dysplasia (32) and arteritis (16), were submitted to
      isolated or associated treatment of renal revascularization by percutaneous
      transluminal angioplasty (71 patients) or surgery (84). The patients were
      followed-up during 2.5 +/- 1.5 years and we evaluate blood pressure response and
      renal function preservation. In relation to blood pressure control, the patients
      were considered as cured when normotensives without antihypertensives, improved
      when normotensives with fewer drugs than previously, and unchanged, when out of
      these criteria. RESULTS: From 124 patients, 20% were considered cured, 54%
      improved and 26% unchanged, after a mean follow-up of 2.5 +/- 1.5 years. Patients
      with atherosclerosis and fibromuscular dysplasia presented a higher rate of care
      and improvement after surgery. The blood pressure and the number of
      antihypertensive drugs decreased significantly during the follow-up among
      patients that cured or improved arterial hypertension, either after angioplasty
      (190 +/- 26/115 +/- 14 mmHg vs 130 +/- 34/85 +/- 7 mmHg. 2.70 vs 1.60 drugs) or
      after surgery (194 +/- 17/115 +/- 16 mmHg vs 143 +/- 18 mmHg vs 88 +/- 8 mmHg,
      1.88 vs 1.51 drugs). It was also observed a significant decrease of serum
      creatinine among these patients. CONCLUSION: Renal revascularization in patients
      with renovascular hypertension, either by angioplasty or surgery, is beneficial
      to control blood pressure and to preserve renal function in the majority of
      patients.

PMID- 7826236
TI  - [Acute liver failure secondary to cardiogenic shock in patients with congestive
      heart failure].
AB  - Fulminant hepatic failure is a complication of severe cardiocirculatory failure,
      with high morbidity and mortality, and is frequently misdiagnosed as fulminant
      viral hepatitis. We report three cases of patients with chronic severe heart
      failure who developed cardiogenic shock complicated by elevation of
      aminotransferase levels above 1,000 soon after the most severe episode of
      hypotension. All the three patients presented regression of hepatic enzymes 72h
      after admission. Two patients developed hepatic encephalopathy and renal failure.
      One underwent the implantation of an artificial left ventricle, followed by
      orthotopic heart transplantation. One died of systemic multiple organ failure,
      after he had showed improvement on his hepatic profile, and one was sent to the
      ward, after 15 days with marked improvement on his clinical status and no signs
      of hepatic disease.

PMID- 7826237
TI  - [Rupture of the left ventricular free wall. A lethal entity that can be
      surgically treated with success].
AB  - We present three patients with left ventricular free wall rupture post acute
      myocardial infarction, all three treated successfully through surgery. Two of
      them were submitted to streptokinase IV. In all cases the diagnosis were based on
      clinical and echocardiographic features. The authors conclude that the diagnostic
      suspicion can be done easily, the echocardiogram is very useful, and the surgical
      treatment may led to a good short- and long-term survival.

PMID- 7826238
TI  - [Reagudization of Chagas myocarditis inducing exclusive right ventricular
      failure].
AB  - Woman, 42 years-old, receiving immunosuppressive therapy for a lymphoma,
      presented reagudization of Chagas' disease, from its indeterminate phase. Intense
      inflammatory visceral aggression, due to extensive intracellular proliferation of
      the Trypanosoma cruzi, was the likely mechanism for acute myocarditis leading to
      severe right ventricular failure. Antiparasite chemotherapy was effective in the
      control of visceral involvement and for the remission of cardiac failure. The
      clinical course in this case is compatible with the hypothesis of early right
      ventricular damage in Chagas' disease.

PMID- 7826239
TI  - [The importance of stress tests in the diagnosis of arterial hypertension].

PMID- 7826240
TI  - [Clinical manifestations in complex partial crisis of the temporal lobe: a video
      electroencephalographic study].
AB  - We analysed 27 complex partial seizures arising from the temporal lobes recorded
      on videotape simultaneously with the EEG emphasizing the motor manifestations
      specially dystonic posturing, ictal paresis and head and eye forced deviation
      (version). The temporal lobe origin of the seizures was based on the agreement of
      many scalp-sphenoidal or zygomatic interictal and ictal EEG recordings, CT and
      MRI findings, interictal and, in some patients, ictal SPECT studies. 8 patients
      had surgery. In 5 from 7 patients who had temporal lobectomy, mesial temporal
      sclerosis was the anatomopathological finding and in one patient who had
      selective amigdalohippocampectomy, hemosiderosis and gliosis probably due to
      bleeding of a posterior cerebral artery giant aneurysm was found. All patients
      have been seizure free after surgery. While dystonic posturing and ictal paresis,
      present in 18 seizures (66.6%), were excellent as lateralizing seizure signs,
      since they were always contralateral to the ictal onset, contralateral and
      ipsilateral versive head and eye movements were observed.

PMID- 7826241
TI  - [Sex differences of visual attention in cryptogenic partial epilepsy].
AB  - The performance in visual verbal and non-verbal attentional tests was studied in
      14 male and 18 female control subjects and 33 patients with cryptogenic partial
      epilepsy. The epileptic group was formed of 17 men and 16 women with no evidence
      of brain damage in CT scan examinations. Interictal epileptiform activity was
      observed only unilaterally, either in the right (8 male, 8 female) or left (9
      male, 8 female) temporal lobes. The performance of epileptic men in visual tests
      was similar to that of normal men. On the other hand, the performance of
      epileptic women was worse than that of normal women. These results seem in
      accordance with the literature that suggests that visual attention in women
      depends on the functional integrity of both cerebral hemispheres. In men, verbal
      visual attention is suggested to occur in the left cerebral hemisphere while non
      verbal processes, predominantly in the right cerebral hemisphere. Further studies
      are necessary for the understanding of these sexual differences in cerebral
      hemispheric asymmetry.

PMID- 7826242
TI  - MRI and brain spect findings in patients with unilateral temporal lobe epilepsy
      and normal CT scan.
AB  - 26 patients with temporal lobe epilepsy clinically documented by several abnormal
      interictal surface EEGs with typical unitemporal epileptiform activity and a
      normal CT scan were studied. Interictal 99mTC HMPAO brain SPECT and MRI were
      performed in all subjects. Abnormalities were shown in 61.5% of MRI (n = 16) and
      65.4% of SPECT (n = 17). Hippocampal atrophy associated to a high signal on T2
      weighted MRI slices suggesting mesial temporal sclerosis was the main finding (n
      = 12; 75% of abnormal MRI). MRI correlated well to surface EEG in 50% (n = 13).
      There was also a good correlation between MRI and SPECT in 30.7% (n = 8). SPECT
      and EEG were in agreement in 57.7% (n = 15). MRI, SPECT and EEG were congruent in
      26.9% (n = 7). These results support the usefulness of interictal brain SPECT and
      MRI in detecting lateralized abnormalities in temporal lobe epilepsy. On the
      other hand, in two cases, interictal SPECT correlated poorly with surface EEG.
      This functional method should not be used isolately in the detection of temporal
      lobe foci. MRI is more useful than CT as a neuroimaging technique in temporal
      lobe epilepsy. It may detect small structural lesions and mesial temporal lobe
      sclerosis which are not easily seen with traditional CT scanning.

PMID- 7826243
TI  - Clinical factors adversely affecting early outcome after brain infarction.
AB  - PURPOSE AND METHODS: One-hundred-and-nine consecutive patients admitted during
      the acute phase of a CT-confirmed brain infarction (BI) were studied. Putative
      adverse influence of demographic and stroke risk factors, previous medical
      history, clinical presentation, initial and follow-up neurological examination,
      initial general evaluation, laboratory findings, chest X-ray and
      electrocardiographic findings, treatment, and topography and etiology of the
      ischemic insult was analysed. The end-point for assessment was early death
      (within 30 days). Statistical analysis was performed with univariate analysis and
      multiple regression. RESULTS: The main adverse factors related to an increased
      death risk during the first 30 days were, in decreasing order of importance: coma
      48-72 hours after admission; stroke occurring in already hospitalized patients;
      Babinski sign on admission; minor degrees of impairment of consciousness 48-72
      hours after admission; stroke related to large artery atherothrombosis and to
      embolism; a history of early impairment of consciousness; cardiac failure on
      admission. In 53 lucid patients on admission, only a history of congestive heart
      failure (CHF) was associated with a reduced survival rate. In 56 patients with
      impaired consciousness, the presence of a Babinski sign increased death risk, but
      the main factor predicting a high case-fatality rate was the persistence of
      consciousness disturbances after 48-72 hours. CONCLUSIONS: The presence of
      impairment of consciousness, especially coma, 2-3 days after disease onset, and a
      history of CHF greatly increase the early case fatality rate in patients with
      acute BI presenting with or without consciousness disturbances at admission,
      respectively. The use of a prognostic algorythm considering these few variables
      seems to predict the approximate 30-day fatality rates.

PMID- 7826244
TI  - [Essential tremor: clinical characterization in a sample of 176 patients].
AB  - We reviewed the clinical records of 176 patients with essential tremor (ET)
      according to sex, age of onset, family history, tremor characteristics and body
      distribution. The patients were divided into two groups: familial (F) and non
      familial (NF). A positive family history for tremor was observed in 47.2% of the
      patients. Action and postural tremor were the most frequent characteristic
      (49.4%), postural alone in 26.7% and action alone in 9.1%. Rest tremor was
      recorded in 10.2%, always associated with other characteristics. There were no
      clinical differences between the F and NF groups. Hands were involved in 94.9%
      and the head in 26.5%. Isolated tremor of the hands was the most frequent form of
      presentation with some greater frequency in males. Sixty per cent of the patients
      who presented head tremor either isolated or not, were females. The presence or
      absence of family history did not show difference in this proportion. The age of
      onset ranged between 4 and 85 years. In the F group a lower mean of onset (36.5
      years) was seen in males with statistical significance. In male patients with
      combined action and postural tremor a lower age of onset was found. The fact of a
      patient having either parent affected by ET produced no difference in the age of
      onset. Familial or non familial ET bearing some differences, may not be
      considered as distinct entities.

PMID- 7826245
TI  - Cysticercosis of the central nervous system. I. Surgical treatment of cerebral
      cysticercosis: a 23 years experience in the Hospital das Clinicas of Ribeirao
      Preto Medical School.
AB  - Cysticercosis is the most frequent parasitosis of the nervous system and nowadays
      it is widespread through the world. Despite the development of anticysticercal
      drugs (praziquantel and albendazole), their efficacy is more marked in cases with
      parenchymal active cysts and they do not prevent complications such as
      hydrocephalus. Thus, many patients with neurocysticercosis require surgical
      intervention, generally of palliative nature, but that may occasionally produce a
      cure. The clinical outcome of 180 patients with cerebral cysticercosis who
      underwent surgical treatment form 1970 to 1993 was analyzed. Surgical treatment
      was performed to control increased ICP in 177 patients and due to local
      compression of cranial nerves or brainstem in five. Some patients had more than
      one surgical procedure, totalizing 287 interventions. Increased intracranial
      pressure (ICP) was caused by hydrocephalus in 91%, by intracranial mass lesion
      (tumoral form) in 6.2% and by pseudotumor cerebri (pseudotumoral form) in 2.8% of
      the case. Based on the pathophysiological mechanisms of intracranial hypertension
      identified through conventional CT-scan, ventriculography, cysternotomography,
      ventriculotomography and MRI, different surgical approaches were indicated.
      Patients with tumoral form were submitted to direct approach and cyst removal and
      generally they had benefits from this procedure. Patients with pseudotumoral form
      whose clinical treatment failure underwent decompressive craniectomies and had a
      poor outcome (40% of good results). Direct removal of ventricular/cisternal cysts
      and/or ventriculoatrial/peritoneal shunting (VA/VPS) was performed in patients
      with hydrocephalus. Removal of free ventricular cysts in patients who had no
      ependimitis/arachnoiditis generally allowed a good outcome. Patients with
      adherent cysts and inflammatory process needed a VA/VPS posteriorly and the
      outcome was not so good. One hundred thirty-two patients were submitted to VA/VPS
      (109 as the first procedure and 23 after another surgical treatment). The VA/VPS
      was effective to control increased ICP, despite many complications observed
      mainly during the two first postoperative years. After this period the surviving
      patients generally had a better outcome. The patients submitted to cyst removal
      due to local compression of cranial nerves/brainstem generally had good results.
      Based on the experience acquired with the management of these patients we present
      our recent policy for the treatment of patients with neurocisticercosis.

PMID- 7826246
TI  - Cysticercosis of the central nervous system. II. Spinal cysticercosis.
AB  - The compromising of the spinal canal by cysticercus is considered infrequent,
      varying from 16 to 20% in relation to the brain involvement. In the spinal canal
      the cysticercus predominantly places in the subarachnoid space. Clinical signs in
      spinal cysticercosis can be caused by direct compression of the spinal cord/roots
      by cysticerci and by local or at distance inflammatory reactions (arachnoiditis).
      Another mechanism of lesion is degeneration of the spinal cord due to
      pachymeningitis or circulatory insufficiency. The most frequent clinical features
      are signs of spinal cord and/or cauda equina compression. The diagnosis of spinal
      cysticercosis is based on evidence of cerebral cysticercosis and on
      neuroradiological examinations (myelography and myelo-CT) that show signs of
      arachnoiditis and images of cysts in the subarachnoid space and sometimes, signs
      of intramedullary lesions, but the confirmation can only be made through
      immunological reactions in the CSF or during surgery. The clinical course of 10
      patients with diagnosis of spinal cysticercosis observed among 182 patients
      submitted to surgical treatment due to this disease are analyzed. The clinical
      pictures in all cases were signs of spinal cord or roots compression. All but two
      presented previously signs of brain cysticercosis. Neuroradiological examinations
      showed signs of arachnoiditis in 4 patients, images of cysts in the subarachnoid
      space in 5, and signs of arachnoiditis and images of cysts in one. The 6 patients
      that presented intraspinal cysts were submitted to exeresis of the cysts and 2
      patients with total blockage of the spinal canal underwent surgery for diagnosis.
      The 2 remaining patients with arachnoiditis and blockage of the spinal canal were
      clinically treated. All of the six patients submitted to cyst exeresis had
      initial improvement but 4 of them later developed arachnoiditis and recurrence of
      the clinical signs and only 2 remained well for long-term. The 2 non operated
      patients had no improvement of their clinical signs. Two patients died later due
      to complications of cerebral cysticercosis. Based on the experience acquired in
      the management of these patients we indicate surgical treatment for patients that
      present free cyst in subarachnoid space. For those who present arachnoiditis,
      surgery is indicated only when there is doubt in the diagnosis. Intramedullary
      cysts should also be surgically treated.

PMID- 7826247
TI  - Cognitive impairment in human chronic Chagas' disease.
AB  - We proposed to investigate subclinical cognitive impairment secondary to chronic
      Chagas' disease (CCD). No similar study was previously done. The
      neuropsychological performance of 45 chronic Chagasic patients and 26 matched
      controls (age, education place and years of residency in endemic area) was
      compared using the Mini Mental State Exam (MMSE), Weschler Memory Scale (WMS) and
      the Weschler Adult Intelligent Scale (WAIS). Non-parametric tests and Chi2 were
      used to compare group means and multivariate statistics in two way frequency
      tables for measures of independence and association of categorical variables with
      the disease. RESULTS: Chagasic patients showed lower MMSE scores (p < .004), poor
      orientation (p < .004), and attention (p < .007). Lower WMS MQ were associated
      with CCD (Chi2 5.9; p < .01; Fisher test p < .02). Lower WAIS IQ were associated
      with CCD (Chi2 6.3, p < .01; Fisher test p < .01) being the digit symbol (p <
      .03), picture completion (p < .03), picture arrangement (p < .01) and object
      assembly (p < .03) subtests the most affected. The impairment in non-verbal
      reasoning, speed of information processing, problem solving, learning and
      sequencing observed in chronic Chagas disease patients resembles the cognitive
      dysfunction associated with white matter disease.

PMID- 7826248
TI  - Dichotic words listening test. Technical aspects and results in normal right
      handed individuals.
AB  - Dichotic listening tests have been being used in an increasing frequency to
      determine in a non-invasive way the cerebral dominance in right- and left-handed
      patients. This is especially relevant when surgery in eloquent brain areas is
      being contemplated. A Portuguese version of the dichotic words listening test was
      developed based mainly on Wexler's protocol. It consisted of 15 pairs of words
      with a stimulus dominance lower than 50%. They were recorded using natural voice
      and time and intensity synchronization by means of a specialized software. Each
      pair of words was presented twice in different channels within each block. The
      items were randomized and presented with a 300 msec interval between each trial.
      Four blocks of 30 pairs of words each were created, totalizing 120 trials. In the
      scoring process, the words heard over the right and left ears were wrote down.
      The number of times each word was heard over each ear was computed and their
      values subtracted yielding a partial score for each specific word pair. This
      process was repeated for all stimuli pair and a final score for right and left
      predominance was then reached. Thirty-two right handed normal individuals
      underwent the test. 93.8% showed a right ear advantage. These results are very
      similar to the actual left hemisphere dominance rate in a right-handed
      population.

PMID- 7826249
TI  - Carbamazepine kinetics in cardiac patients before and during amiodarone.
AB  - Carbamazepine and amiodarone may often be used together, especially in countries
      where cardiomyopathies are common. In this study single doses of carbamazepine
      (400 mg) were given to patients with cardiac disease before and after one month
      of therapy with amiodarone, 400 mg daily. The kinetic profile of carbamazepine,
      its free fraction, and serum amiodarone, were measured at the two occasions.
      There was no statistically significant change in carbamazepine kinetics or free
      fraction, before and after the introduction of amiodarone. The concentrations of
      amiodarone after one month of therapy were low. It is suggested that the possible
      interaction in the hepatic metabolism was not demonstrated because amiodarone
      concentrations were not enough to inhibit carbamazepine metabolism.

PMID- 7826250
TI  - [Increase of interleukin-2 soluble receptors in multiple sclerosis: preliminary
      study in 26 patients].
AB  - Serum samples were analysed for interleukin-2 receptors levels (sIL-2R) in 26
      patients with definite multiple sclerosis as defined by Poser and col. Three
      groups of patients form the basis of this study: group I, with 14 patients with
      clinical evidence of active disease; group II, with 12 patients with clinically
      stable multiple sclerosis; and group III, with 8 patients with other neurological
      diseases. Blood was collected by venipuncture and centrifuged. All samples were
      stored at -20 degrees C until testing. The assay used monoclonal antibodies
      against epitopes of interleukin-2 receptors. In the wells of a microtiter plate
      coated with anti-soluble interleukin-2 receptors (Immunotech SA) samples to be
      measured or standards are incubated in the presence of a second monoclonal
      antibody conjugated with alkaline phosphatase. The amount of bound enzyme
      conjugate is measured by adding a chromogenic substrate. The intensity of the
      resulting colour is proportional to the sIL-2R concentration present in the
      sample. Increased serum levels of sIL-2R were found in 7 of 14 patients with
      active multiple sclerosis (50%), in only 1 of the 12 patients with clinically
      stable multiple sclerosis and in none of the patients with other neurological
      diseases.

PMID- 7826251
TI  - [Poliomyelitis in Sergipe].
AB  - A retrospective study of poliomyelitis in Sergipe, Northeast of Brazil, is
      presented by the authors. The study was divided in three periods, taking in
      consideration the notification rate of positive cases and emphasizing the period
      from 1979 to 1989 through the study of 159 consecutive cases. The following
      information was gathered for each case: sex, age, origin, former immunization
      status and clinical development. Also evaluated were annual incidence,
      relationship of incidence/vaccinal coverage and geographic distribution. Comments
      were made about the change in the wild poliovirus circulation (P1 to P3) and
      about epidemiological outbreaks occurred in 1984 and 1986, and problems related
      to the lack of immunity in children with complete vaccinal scheme. Poliomyelitis
      was considered to be controlled in the State of Sergipe but the necessity of
      maintenance of effective epidemiological vigilance for all cases of acute and
      flabby paralysis in children under 14 years is emphasized.

PMID- 7826252
TI  - [Modified lateral approach for surgery of thoracic disk herniation. Technical
      note].
AB  - The thoracic spine may be approached by different ways: posterior,
      posterolateral, anterolateral and anteriorly, with associated removal of diverse
      osseous structures as facet joints, costal processes, pedicles and ribs,
      subsequently imposing the use of diverse fusion procedures in some cases. The
      extreme lateral approach to the thoracic disc space produces minimum disruption
      of the normal spinal musculoskeletal anatomy, avoids retraction of the spinal
      cord and preserves the intercostal neurovascular bundle and the segmental
      radicular arteries. The operation is carried out with the patient in the prone
      position, and the patient is rotated away from the surgeon as necessary when the
      deeper levels are accessed. Radioscopy is used to identify the correct level
      after positioning of the patient. A straight transversal paravertebral incision
      is recommended in single-level operations. Alternatively an elliptical incision,
      concave medially and centered at the marked rib, is done and the skin flap is
      refleted medially. The muscles are partially divided at right angles over the rib
      to be excised and refleted cranial and caudally, exposing the rib and transverse
      process. The target disc is approached by removal of about 5 cm of the rib which
      has its insertion at the disc level, if necessary associated with partial removal
      of the transverse process, followed by partial pediculotomy (exclusively at the
      base of the pedicle) and a little lateral rachotomy (vertebral body ressection),
      which permits opening of the spinal canal exclusively ventral to the
      intervertebral foramen. In this way any kind of hemilaminectomy or facectomy is
      avoided. The discectomy is then carried out. This is a minimally invasive
      approach in comparison to the current ones.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7826253
TI  - [Orbital phlebography evaluation in 8 cases of Tolosa-Hunt syndrome].
AB  - Tolosa-Hunt syndrome (THS), or painful ophthalmoplegia is associated to a non
      specific granulomatosis of unknown etiology, that involves the superior orbital
      fissure and its nervous and vascular structures. The clinical picture that
      responds to steroid therapy, is variable and is always associated with pain.
      Inflammatory conditions, tumors and aneurysms can produce similar symptoms.
      Computed tomography, cerebral angiography and orbital phlebography are the
      imaging methods of choice for making the diagnosis. We revised the results of
      these radiological examinations of eight patients seen at the Hospital Sao Paulo
      from 1989 to 1991, with the diagnosis of THS according to Hunt and Hannerz
      criteria. The analysis of orbital phlebographic changes based upon Hannerz et al.
      systematization showed non-specific features, but those were able to help the
      diagnosis.

PMID- 7826254
TI  - [Intracranial cavernous angioma].
AB  - Clinical, radiological and histopathological features of eight cases of
      symptomatic cavernous angioma are presented. Five patients were being evaluated
      for seizure, two for mass lesions and one for intracranial hemorrhage. CT and/or
      MRI detected the lesion in all cases, but there is not a characteristic image for
      cavernous angioma. Good results were obtained by microsurgical approach to these
      malformations in seven patients with only one patient suffering a worsening of
      neurological status after surgery.

PMID- 7826255
TI  - [Magnetic resonance imaging in spinal dysraphisms].
AB  - We studied by magnetic resonance imaging the incidence of associated
      malformations in a group of 38 patients with diagnosis of spina bifida followed
      in our outpatient clinic. Twenty-two children were born with spina aperta and 16
      with spina bifida occulta. Tethered cord was found in the majority of patients of
      both groups. Syringomyelia was found in 13 patients. The craniocervical region
      was studied in 11 patients with the diagnosis of spina bifida aperta; Chiari
      malformation was found in 8. The results point to the fact that asymptomatic
      malformations detected by MRI techniques are frequent in patients with spina
      bifida.

PMID- 7826256
TI  - [Benign intrinsic tectal tumors: apropos of 2 cases].
AB  - The introduction of computerized tomography and magnetic resonance imaging led to
      the knowledge that brain stem tumors are not a homogeneous group with regard to
      their clinical, pathological and biological features. The classical concept of an
      uniformly poor prognosis has been modified and some subtypes of tumors are
      amenable to surgical treatment and long-term survival. The authors report two
      cases of patients with tumors of the tectal region whose symptoms and CT features
      were consistent with late-onset aqueductal obstruction. In both cases definitive
      diagnosis was established by MRI and symptoms resolved after ventriculo
      peritoneal shunt implantation. The clinic and pathological features and
      therapeutical alternatives as well, are discussed.

PMID- 7826257
TI  - [Temporal lobe epilepsy and aura with happiness and pleasure: report of 2 cases
      and review of the literature].
AB  - The authors present two cases of temporal lobe epilepsy with happiness and
      pleasure during the seizure. Discussing the rarity of these clinical findings,
      the concept of epileptic aura is historically reviewed with special attention to
      Dostoievski's epilepsy and its descriptions by the medical literature.

PMID- 7826258
TI  - Midazolam for treatment of refractory neonatal seizures. A case report.
AB  - Midazolam is a short-acting water soluble benzodiazepine that has been used with
      an increasing frequency in the last years. Although there are reports on its use
      in status epilepticus, there is none in the neonatal period. A pre-term (35 w)
      AGA newborn infant with a severe hypoxic-ischemic encephalopathy secondary to
      grade III hyaline membrane disease developed status epilepticus in the first 6
      hours of life and was successfully treated with midazolam after phenobarbital and
      phenytoin failed to achieve seizure control. Dosage schedule was 0.2 mg/kg IV,
      followed by continuous infusion of 0.025 mg/kg/h. Midazolam is an effective drug
      for neonatal status epilepticus and more experience should accumulate before it
      can be routinely employed in the neonatal period. This case shows that it is a
      possible option before using more dangerous drugs, such as thionembutal.

PMID- 7826259
TI  - [Hemiballismus as initial manifestation of acquired immunodeficiency syndrome: a
      case report].
AB  - There are few descriptions of movement disorders as an initial presentation of
      acquired immunodeficiency syndrome (AIDS). The authors report the case of a 54
      year-old man who presented with hemiballismus of gradual onset. The computed
      axial tomographic scan showed a deep seated enhancing lesion with mass effect.
      Investigation revealed AIDS and a probable toxoplasmosis. It is concluded that
      AIDS must be considered in the aetiological diagnosis of patients with movement
      disorders.

PMID- 7826260
TI  - [Cerebral hydatid cyst in children in the Hospital Nacional Cayetano Heredia:
      apropos of a case].
AB  - Case report of a 12 years old female child who developed in the last seven months
      focal neurological signs and progressive intracranial hypertension. CT scan
      showed a giant cystic tumor, and cerebral hydatidosis has been diagnosed. The
      hydatic cyst was surgically removed without complications. Cerebral hydatidosis
      is rare, its diagnosis is clinical and tomographic, and the treatment is always
      surgical.

PMID- 7826261
TI  - [Botulinum toxin the treatment of spasmodic torticollis: a meta-analysis].
AB  - The authors made a meta-analysis of the results of botulinum toxin injection for
      the treatment of spasmodic torticollis. They concluded that botulinum toxin is
      effective for the treatment of cervical dystonia.

PMID- 7826262
TI  - Yawning.
AB  - The ubiquitousness of normal yawning and the existence of abnormal yawning
      warrant an understanding of this reflex. Its mechanisms and functional role are
      not entirely known. A review of the literature reveals that yawning is a brain
      stem arousal reflex with both peripheral and central loops subserving reversal of
      brain hypoxia or hypoxemia. Behaviorally, yawning is a semi-involuntary act that
      occurs also because of loss of interest in the surroundings and it is not
      necessarily associated with fatigue. Socio-environmental factors can influence
      the emergence of yawning. Dopaminergic, acetylcholinergic, ACTHergic and
      oxytocinergic systems are involved in the generation and modulation of yawning in
      animal experimentation.

PMID- 7826263
TI  - [Cerebrovascular disorder or brain vascular disease? Reviewing the designation
      and respecting the anatomy].

PMID- 7826264
TI  - Epilepsy is not a disease. Proposal for a new approach in the International
      Classification of Diseases (ICD).
AB  - What is epilepsy? a disease? a symptom? a syndrome? is it important to define it?
      Basing his study on an extensive bibliography, the author shows that epilepsy is
      not a disease. He emphasizes the significance of that definition and suggest a
      new approach in the International Classification of Diseases (ICD).

PMID- 7826265
TI  - Alzheimer's disease presenting as slowly progressive aphasia and slowly
      progressive visual agnosia: two early reports.

PMID- 7826266
TI  - Zinc-induced deterioration in Wilson's disease aborted by treatment with
      penicillamine, dimercaprol, and a novel zero copper diet.

PMID- 7826267
TI  - Medical treatment of cysticercosis--ineffective.

PMID- 7826268
TI  - Medical treatment of cysticercosis--effective.

PMID- 7826269
TI  - Medical treatment of cysticercosis.

PMID- 7826270
TI  - Nonprovider factors that impact health care cost and access.

PMID- 7826271
TI  - Lack of relationship between leukoaraiosis and carotid artery disease. The North
      American Symptomatic Carotid Endarterectomy Trial.
AB  - OBJECTIVE: Leukoaraiosis (LA) (white matter changes) is frequently observed on
      computed tomographic scans of the brain of elderly patients at risk of stroke. A
      localized vascular-ischemic cause has been suggested for its underlying
      mechanism. Our aim was to assess whether high-grade carotid stenosis is
      associated with LA. DESIGN/SETTING: Patients enrolled in the North American
      Symptomatic Carotid Endareterectomy Trial (also known as NASCET) were evaluated
      for LA using a recently proposed grading scale. Ordinal regression analysis was
      used to assess the association between the severity of carotid artery stenosis
      and the extent of LA observed on computed tomographic scans. The patients' brain
      hemisphere was selected as the unit of analysis. RESULTS: Of the 2394 brain
      hemispheres contributed to the analyses, 352 (14.7%) had signs of LA. After
      controlling for known stroke risk factors in the ordinal regression analysis,
      only the history of stroke and increasing age were significantly related to LA.
      Severity of stenosis was observed to be unrelated (odds ratio [severe vs mild
      stenosis] = 1.08; 95% confidence interval, 0.73-1.62; P = .952) as were a history
      of hypertension and a history of myocardial infarction. CONCLUSION: Leukoaraiosis
      is not associated with severe carotid artery stenosis.

PMID- 7826272
TI  - Proximal myotonic myopathy. Clinical features of a multisystem disorder similar
      to myotonic dystrophy.
AB  - BACKGROUND: Previous investigations in three families have shown that proximal
      myotonic myopathy (PROMM) is not linked to the gene loci for myotonic dystrophy
      (DM) or to the loci of the genes of the muscle sodium and chloride channels
      associated with other myotonic disorders. It is important to extend our clinical
      knowledge of this interesting new disorder by studying other families. PATIENTS:
      Thirty-five patients in 14 new families; 27 patients were examined. METHODS:
      Clinical examination, electromyography, muscle biopsy, DNA analysis. RESULTS: The
      following findings were noted: proximal without distal weakness of the legs (n =
      21); myotonia on electromyograms (n = 23); intermittent clinical myotonia (n =
      17); cataracts (n = 24) and a number of the cataracts were identical to the type
      in DM (n = 11); and peculiar muscle pain (n = 14). A few patients had cardiac
      arrhythmias, and others had elevations in the concentrations of serum gamma
      glutamyltransferase. None of the patients had significant muscle atrophy. Muscle
      biopsy specimens showed mild myopathic changes. All patients had normal
      trinucleotide (cytosine, thymine, and guanine) repeat size of the DM gene in
      leukocyte DNA. Muscle DNA probes from three patients showed findings identical to
      those of their leukocyte DNA probes. CONCLUSIONS: Proximal myotonic myopathy is a
      new genetic disorder similar to, but distinct from, DM. Patients suspected of
      having DM but with negative DNA studies may have PROMM. The gene defect for PROMM
      awaits discovery. Because of the similarities between PROMM and DM, this
      discovery will not only shed light on the pathomechanism of PROMM, but it may
      also increase our understanding of DM.

PMID- 7826274
TI  - Correlation between computed tomographic brain scan abnormalities and
      neuropsychological function in children with symptomatic human immunodeficiency
      virus disease.
AB  - OBJECTIVE: To evaluate the clinical significance of computed tomographic brain
      scan abnormalities observed in children with symptomatic human immunodeficiency
      virus disease. PATIENTS: Eighty-seven previously untreated children with
      symptomatic human immunodeficiency virus type 1 disease. METHODS: General levels
      of cognitive functioning, obtained from age-appropriate intelligence tests, and
      social-emotional behavior were correlated with computed tomographic brain scan
      abnormality ratings. RESULTS: A significant relation between computed tomographic
      brain scan abnormalities and cognitive dysfunction as well as aberrant behavior
      was found, which appeared stronger in (younger) vertically infected children
      compared with transfusion-infected patients. Calcifications, independent from the
      degree of brain atrophy, were associated with significantly greater delays in
      neurocognitive development. CONCLUSION: Computed tomographic brain scan
      abnormalities, even when mild, were of clinical significance, suggesting that
      human immunodeficiency virus-associated central nervous system compromise is a
      continuous process and that scans may be helpful at baseline in defining patients
      at risk and for monitoring them during therapy.

PMID- 7826273
TI  - Dyslexia and corpus callosum morphology.
AB  - OBJECTIVE: There is evolving evidence that developmental dyslexia is associated
      with anomalous cerebral morphology in the bilateral frontal and left
      temporoparietal regions. This study examined the morphology of the corpus
      callosum, as possible deviations in other important structures are poorly
      understood in this behaviorally diagnosed syndrome. DESIGN: Magnetic resonance
      imaging scans were obtained from children with developmental dyslexia and from
      matched control children. Morphometric measurements were examined to determine if
      regional differences existed in the corpus callosum between these two groups of
      children. SETTING: Magnetic resonance imaging studies were completed at Athens
      (Ga) Magnetic Imaging. PATIENTS AND OTHER PARTICIPANTS: Sixteen developmental
      dyslexic children (mean age, 9.7 years) and a matched sample of children who were
      diagnosed as being normal were examined by using a reliable comprehensive
      diagnostic process. MAIN OUTCOME MEASURES: Using a midsagittal magnetic resonance
      imaging scan, corpus callosum morphology was evaluated by segmenting the corpus
      callosum into five regions of interest. RESULTS: Analysis of the corpus callosum
      revealed that the anterior region of interest (the genu) was significantly
      smaller in the dyslexic children. Significant correlations existed between
      reading achievement and the region-of-interest measurements for the genu and
      splenium. Measured intelligence, chronologic age, and gender were not related to
      region-of-interest measurements of the corpus callosum. Consistent with previous
      studies, the dyslexic individuals were characterized by significant psychiatric
      comorbidity, particularly attention-deficit disorder with and without
      hyperactivity. Reported familial left-handedness also distinguished the dyslexic
      children. CONCLUSIONS: Subtle neurodevelopmental variation in the morphology of
      the corpus callosum may be associated with the difficulty that dyslexic children
      experience in reading and on tasks involving interhemispheric transfer.

PMID- 7826275
TI  - Autonomic and peripheral neuropathies in patients with chronic alcoholism. A dose
      related toxic effect of alcohol.
AB  - OBJECTIVE: To assess autonomic and peripheral nervous system function in patients
      with chronic alcoholism. DESIGN: A cross-sectional study. PATIENTS: A consecutive
      sample of 107 alcoholic patients and 61 controls. MAIN OUTCOME MEASURE: For
      autonomic assessment, heart rate variations during deep breathing and Valsalva
      maneuver and on standing were measured. Blood pressure response to standing up
      and to sustained handgrip were also evaluated. For assessment of the peripheral
      nervous system, an electrophysiologic examination was performed. RESULTS:
      Alcoholic patients exhibited reduced heart rate variability compared with
      controls (P < .01, on all parasympathetic tests), whereas no differences in the
      mean values of the blood pressure responses between both groups were found.
      Twenty-six patients (24.3%) had criteria of autonomic neuropathy, and 34 (32%)
      had electrophysiologic criteria of peripheral neuropathy. None of the controls
      exhibited criteria of autonomic neuropathy, and only one had criteria of
      peripheral neuropathy. The estimated total lifetime dose of alcohol correlated
      inversely with the parasympathetic indexes (r = -.48 to -.51; P < .001 on all
      parasympathetic tests) and the sensory potential amplitudes of upper and lower
      limbs (r = -.43; P < .001, both limbs). Finally, a significant correlation
      between autonomic and peripheral neuropathies was observed (P = .01). By
      contrast, these lesions were not related to age, nutritional status, or other
      alcohol-related diseases. CONCLUSIONS: Autonomic and peripheral neuropathies are
      common among hospitalized alcoholic patients. Alcohol appears to be toxic to
      autonomic and peripheral nerves in a dose-dependent manner.

PMID- 7826276
TI  - Effect of steady hypothermia and normothermia on multimodality evoked potentials
      in human poikilothermia.
AB  - OBJECTIVE: To assess the effects of steady-state spontaneous hypothermia on
      multimodality evoked potentials and on peripheral nerve conduction in human
      poikilothermia. DESIGN AND SETTING: Case series at a university hospital.
      PATIENTS: Four patients (four women, aged 28 to 37 years) with acquired
      poikilothermia. MAIN OUTCOME MEASURES: Short-latency somatosensory, brain-stem
      auditory, and visual evoked potentials as well as motor and sensory peripheral
      nerve conduction velocity during steady-state spontaneous hypothermia and
      normothermia. RESULTS: The marked latency prolongation of all evoked potentials
      and decreased peripheral nerve conduction velocity observed during steady-state
      spontaneous hypothermia (mean +/- SD core temperature, 33.5 +/- 0.3 degrees C)
      compared with normothermia (36.9 +/- 0.4 degrees C) agrees with previous findings
      during short-term induced hypothermia. CONCLUSIONS: The unequivocal effect of
      sustained mild spontaneous hypothermia on evoked potentials and peripheral nerve
      conduction velocity underlines the importance of meticulous attention to even
      small alterations in core temperature in interpreting neurophysiological
      investigations.

PMID- 7826277
TI  - Longitudinal neuropsychological and genetic linkage analysis of persons at risk
      for Huntington's disease.
AB  - OBJECTIVE: To determine (1) whether the neuropsychological profiles of healthy
      individuals at risk (AR) for Huntington's disease who were positive (AR/+) or
      negative (AR/-) for the Huntington's disease genetic marker differed from those
      of symptomatic patients with Huntington's disease and normal control individuals
      and (2) whether the neuropsychological performance of the two AR groups differed
      from each other on three assessments during a 4-year span. DESIGN: Case-control,
      double-blind study, with AR status determined by genetic linkage analysis (G8
      probe), in addition to examination of trinucleotide repeats for most AR subjects.
      SETTING: The Neuropsychology Program in the Department of Psychiatry and the
      Department of Neurology at the University of Michigan Medical Center, Ann Arbor,
      a tertiary care center. PARTICIPANTS: Eight subjects matched as closely as
      possible for age, gender, and education in each of the following groups: AR/+,
      AR/-, normal control, and Huntington's disease. MEASURES: A battery of
      neuropsychological tasks, including measures of intelligence, memory, problem
      solving, and motor ability. RESULTS: Although both AR groups demonstrated
      variability on select intellectual subtests relative to normal subjects, they did
      not differ from each other on the three assessments during a 4-year span.
      Patients with Huntington's disease performed more poorly than the other groups
      across a range of neuropsychological measures. CONCLUSIONS: These results do not
      support previous evaluations concluding that AR/+ individuals demonstrate
      cognitive impairments as compared with AR/- individuals. Findings in earlier
      studies without genetic linkage analysis of lower performance of AR individuals,
      including children, as compared with normal controls may relate to extraneous
      environmental and familial issues that interfere with intellectual development.

PMID- 7826278
TI  - Cerebrospinal fluid treponemal antibodies in untreated early syphilis.
AB  - OBJECTIVE: Examine prevalence and diagnostic utility of cerebrospinal fluid (CSF)
      treponemal antibodies in early syphilis. DESIGN: Comparison study. SETTING:
      Sexually transmitted diseases clinic. PATIENTS: Forty patients with untreated
      early syphilis who underwent lumbar puncture. Fifteen were human immunodeficiency
      virus seropositive. MEASUREMENTS: Cerebrospinal fluid cell count, protein, VDRL
      test, and antibodies to Treponema pallidum by microhemagglutination test for T
      pallidum (MHA-TP) and fluorescent treponemal antibody absorption test (FTA-ABS);
      albumin ratio; and IgG index. RESULTS: Cerebrospinal fluid cell count was not
      available for one sample, and this patient was excluded from analysis. Of 39
      patients, eight (21%) had reactive CSF-VDRL (definite neurosyphilis). Eleven
      (28%) had mildly elevated cell count or protein concentration, but nonreactive
      CSF-VDRL (possible neurosyphilis). Twenty had normal cell count and protein
      concentration, and non-reactive CSF-VDRL (normal). Cerebrospinal fluid MHA-TP and
      CSF FTA-ABS were reactive in all eight with neurosyphilis. Cerebrospinal fluid
      MHA-TP was reactive in seven (70%) of 10 with possible neurosyphilis and in six
      (32%) of 19 with normal CSF. Cerebrospinal fluid FTA-ABS was reactive in four
      (36%) of 11 with possible neurosyphilis and in five (28%) of 18 with normal CSF.
      A reactive CSF treponemal test was associated with higher mean CSF cell count and
      reactive CSF-VDRL. CONCLUSION: When criteria to define neurosyphilis depend on
      cell count or CSF-VDRL reactivity, the sensitivity of CSF treponemal antibodies
      is high. Nonreactive CSF treponemal tests may help to exclude a diagnosis of
      neurosyphilis in patients with early syphilis.

PMID- 7826279
TI  - Cranial nerve preservation after stereotactic radiosurgery for small acoustic
      tumors.
AB  - OBJECTIVE: To assess those factors associated with and predictive of cranial
      nerve preservation after stereotactic radiosurgery in patients with small
      acoustic tumors identified by magnetic resonance imaging. DESIGN: We performed a
      retrospective analysis of our experience with 31 patients with preserved hearing
      and acoustic tumors measuring 10 mm or smaller (pons-to-petrous dimension). All
      patients underwent clinical and audiologic evaluations varying from 6 to 48
      months (mean, 20 months) after stereotactic radiosurgery performed with use of
      the 201 source cobalt 60 gamma unit. RESULTS: Stabilization or reduction in tumor
      volume was achieved in 29 of 31 patients. One patient required delayed
      microsurgical resection. Useful hearing (pure tone average < or = 50 dB and
      speech discrimination score > or = 50%) preservation was achieved in 10 of 10
      patients immediately postoperatively, eight of 10 patients at 6 months, six of 10
      patients at 1 year, and five of 10 at 2 years. Preservation of some measurable
      hearing was possible in all patients immediately after radiosurgery, in 84% and
      in more than half of patients at 2 years. Preoperative facial nerve function was
      preserved in 19 of 20 patients at 2 years after radiosurgery. All patients
      returned to their preoperative employment status within 2 to 5 days after
      radiosurgery. CONCLUSION: Stereotactic radiosurgery performed with current
      technology (multiple radiation isocenters and magnetic resonance imaging
      guidance) is a safe and effective management strategy for patients with small
      acoustic tumors. The risk of facial and trigeminal neuropathy after gamma knife
      radiosurgery is low, and useful hearing can be preserved in up to 50% of patients
      with useful preoperative hearing. Stereotactic radiosurgery is a valuable
      alternative strategy to surgical removal for many patients with newly diagnosed
      small acoustic tumors.

PMID- 7826280
TI  - Neocortical neurofibrillary tangles correlate with dementia severity in
      Alzheimer's disease.
AB  - OBJECTIVE: To determine the relationships between dementia severity and the
      extent of histopathologic lesions in a variety of brain regions. Neocortical and
      hippocampal ratings for neurofibrillary tangles (NFTs) and senile plaques (SPs)
      were compared in 70 cases of clinically and neuropathologically confirmed
      Alzheimer's disease. DESIGN: Neuropathologic case series. Dementia severity was
      assessed by postmortem chart review with use of the extended Clinical Dementia
      Rating Scale (CDR). Linear association between CDR scores and NFT and SP scores
      were assessed by partial correlation, controlling for age at death. SETTING:
      Studies were conducted at the Alzheimer's Disease Research Center of the Mount
      Sinai Medical Center, New York, NY. MAIN OUTCOME MEASURE: Association between CDR
      scores and neuropathologic changes assessed with the Consortium to Establish a
      Registry for Alzheimer's Disease semiquantitative scale. RESULTS: Among these
      lesion scores, only NFTs showed a significant association with CDR score, and
      only for neocortical regions. In particular, NFT densities in the superior
      temporal cortex were most strongly correlated with dementia severity, followed by
      those in the inferior parietal and midfrontal cortex. No such correlations were
      apparent for the amygdala, hippocampus, or entorhinal cortex. Medial temporal
      lobe structures displayed high NFT scores, even in cases of mild dementia. Senile
      plaques did not correlate significantly with CDR score in any region.
      CONCLUSIONS: These data support the notion that neocortical neuronal
      degeneration, as indicated by NFT formation, is a critical determinant of the
      clinical progression of Alzheimer's disease and suggest that medial temporal lobe
      structures may represent the initial site of NFT formation. While SP density
      correlates with age at death, there is no correlation between SP counts and
      dementia severity. These results further suggest that the clinical presentation
      of dementia may be closely related to neurodegeneration in neocortical regions
      within the temporal lobe.

PMID- 7826281
TI  - Phospholipid abnormalities in early Alzheimer's disease. In vivo phosphorus 31
      magnetic resonance spectroscopy.
AB  - OBJECTIVE: To determine whether changes in phosphomonoester and phosphodiester
      levels could be detected in vivo with phosphorus magnetic resonance spectroscopy
      in the early stage of Alzheimer's disease (AD). DESIGN: Survey-type of case
      control study using neuropsychological testing as criterion standard with blinded
      data analysis. SETTING: Patients were from a neurology clinic in Paris, France.
      The controls were from the community. Magnetic resonance measurements were
      performed in the prefrontal region of the brain with a clinical 1.5-T scanner.
      Blinded data analysis. PARTICIPANTS: Twenty-four patients with mild AD and 15 age
      matched healthy volunteers. Subjects were separated into two groups, both
      composed of patients with AD and healthy volunteers. Two successive acquisition
      protocols were used in the two groups. RESULTS: A significant increase in the
      phosphomonoester-total phosphorus ratio was found in patients with AD compared
      with controls. In this series, use of a ratio above 11% as a threshold to test
      our sample yielded an 83.3% sensitivity and a 73.3% specificity test for AD.
      Other metabolite ratios (inorganic phosphate, phosphodiesters, phosphocreatine,
      and nucleotide phosphates to total phosphorus) were not significantly different
      between patients and controls. No metabolite ratio correlated with the
      neuropsychological status as assessed by the Mini-Mental State Examination.
      CONCLUSION: Changes in phospholipid metabolism can be detected in vivo in the
      early stage of AD. Discrepancies in the literature may be due to differences in
      technical setting or in subject population types.

PMID- 7826282
TI  - The age at onset of Alzheimer's disease and an intracranial area measurement. A
      relationship.
AB  - OBJECTIVE: To examine the possibility that premorbid brain size may influence the
      age at onset of symptoms of Alzheimer's disease (AD). DESIGN: Retrospective case
      series. SETTING: Outpatients attending a memory disorders clinic in a tertiary
      referral center. PATIENTS: Twenty-eight female patients with the diagnosis of
      probable AD, selected for the availability of informant derived estimates of age
      at onset of symptoms and computed tomographic scans of the head satisfying
      angulation criteria. MAIN OUTCOME MEASURE: An average intracranial area of two
      adjacent computed tomographic scan sections appropriately angled was used as a
      correlate of premorbid brain size. Strict intracranial volume measurement was not
      performed. RESULTS: Age at onset of symptoms of AD correlated positively (r =
      .48, P = .009) with our measure of premorbid brain size. There was no confounding
      by education, height, or ethnicity. CONCLUSION: Premorbid brain size may be an
      important determinant of the age at onset of symptoms of AD. Epidemiologic
      studies of AD may need to assess the relationship between brain size and putative
      risk factors, eg, low educational attainment, since there is evidence that brain
      size is not distributed uniformly across populations.

PMID- 7826283
TI  - Immunohistochemical localization of fibrillin in human ocular tissues. Relevance
      to the Marfan syndrome.
AB  - OBJECTIVE: To better understand the ocular manifestations of the Marfan syndrome,
      we investigated the distribution of fibrillin in normal human ocular tissues.
      Fibrillin, a microfibrillar glycoprotein component of the extracellular matrix,
      has been found to be the defective gene product in the Marfan syndrome. METHODS:
      Frozen sections from seven pairs of normal eyes were stained with mouse anti
      human fibrillin antibodies using the avidin-biotin immunoperoxidase technique.
      RESULTS: In the anterior segment, the following exhibited positive staining for
      fibrillin: the lens capsule and zonules; connective tissues of the iris, ciliary
      body, ciliary processes, and conjunctiva; and the basement membrane regions of
      the corneal epithelium and endothelium of Schlemm's canal. Posteriorly, fibrillin
      localized to the lamina cribrosa, sclera, choroid, and Bruch's membrane.
      CONCLUSIONS: Fibrillin is widely distributed in ocular connective tissues. The
      implications of defects in these tissues and the resultant ocular abnormalities
      in the Marfan syndrome such as ectopia lentis and glaucoma are discussed.

PMID- 7826284
TI  - Cilia incarnata.

PMID- 7826285
TI  - Iris epithelial ingrowth.

PMID- 7826286
TI  - Conjunctivodacryocystorhinostomy with buccal mucosal graft.
AB  - Conjunctivodacryocystorhinostomy with a borosilicate glass tube (Pyrex tube,
      Gunther Weiss, Scientific Glass Blowing Co, Beaverton, Ore) is the usual
      procedure for a total canalicular block; however, in patients in whom the tube
      comes out, there is a high incidence of closure of the tract. Full-thickness
      buccal mucosa was used to line the conjunctivodacryocystorhinostomy tract in 17
      patients to determine whether the conduit would function adequately without a
      tube. Four patients elected to go without tubes and have remained improved with
      positive results of primary dye tests. The remaining 13 chose to retain their
      tubes.

PMID- 7826287
TI  - Use of the hydroxyapatite ocular implant in the pediatric population.

PMID- 7826288
TI  - Cytomegalovirus retinitis in HIV-infected patients with elevated CD4+ counts.

PMID- 7826289
TI  - Necrotizing keratitis following trabeculectomy with mitomycin.

PMID- 7826290
TI  - Topical cyclosporine for treating necrotizing scleritis.

PMID- 7826291
TI  - Intraocular sustained drug release devices.

PMID- 7826292
TI  - Variation in ophthalmic testing prior to cataract surgery. Results of a national
      survey of optometrists. Cataract Patient Outcome Research Team.
AB  - OBJECTIVE: To assess variation in optometrists' use of ophthalmic tests in the
      evaluation of patients being considered for cataract surgery who have no history
      of other eye disease. DESIGN/PARTICIPANTS: National survey of a systematic sample
      of practicing members of the American Optometric Association (St Louis, Mo), who
      had referred at least one patient to an ophthalmologist for consideration of
      cataract surgery in 1991. RESULTS: Ninety-two of 130 eligible responding
      optometrists reported that they routinely performed preoperative testing on
      patients being considered for cataract surgery. Of these 92 optometrists, 91
      (99%) frequently or always performed refraction, and 82 (89%) frequently or
      always performed a dilated fundus examination in their evaluation of patients
      being considered for cataract surgery who had no history of other eye disease.
      None of these 92 optometrists reported using B-scan ultrasonography or
      electroretinograms frequently or always, and few used A-scan ultrasonography or
      visual evoked responses frequently or always. A substantial percentage frequently
      or always used formal visual field testing (47%), formal color vision testing
      (40%), fundus photography (24%), potential acuity measurement (25%), glare
      testing (23%), contrast sensitivity testing (19%), and specular microscopy (14%),
      while 11% to 81% of optometrists never performed these tests on such patients.
      More recent graduation from optometry school was associated with a decreased
      frequency of use of potential acuity measurement and contrast sensitivity testing
      and with an increased use of dilated fundus examinations. CONCLUSION: There is a
      substantial variation in optometrists self-reported use of a number of ophthalmic
      tests in the preoperative evaluation of patients being considered for cataract
      surgery who have no history of other eye disease.

PMID- 7826293
TI  - The effect of intensive diabetes treatment on the progression of diabetic
      retinopathy in insulin-dependent diabetes mellitus. The Diabetes Control and
      Complications Trial.
AB  - OBJECTIVE: To determine the magnitude of the decrease in the risk of retinopathy
      progression observed with intensive treatment and its relationship to baseline
      retinopathy severity and duration of follow-up. DESIGN: Randomized clinical
      trial, with 3 to 9 years of follow-up. SETTING AND PATIENTS: Between 1983 and
      1989, 29 centers enrolled 1441 patients with insulin-dependent diabetes mellitus
      aged 13 to 39 years, including 726 patients with no retinopathy and a duration of
      diabetes of 1 to 5 years (primary prevention cohort) and 715 patients with very
      mild to moderate nonproliferative diabetic retinopathy and a duration of diabetes
      of 1 to 15 years (secondary intervention cohort). Ninety-five percent of all
      scheduled examinations were completed. INTERVENTIONS: Intensive treatment
      consisted of the administration of insulin at least three times a day by
      injection or pump, with doses adjusted based on self-blood glucose monitoring and
      with the goal of normoglycemia. Conventional treatment consisted of one or two
      daily insulin injections. OUTCOME MEASURES: Change between baseline and follow-up
      visits on the Early Treatment Diabetic Retinopathy Study retinopathy severity
      scale, assessed with masked gradings of stereoscopic color fundus photographs
      obtained every 6 months. RESULTS: Cumulative 8.5-year rates of retinopathy
      progression by three or more steps at two consecutive visits were 54.1% with
      conventional treatment and 11.5% with intensive treatment in the primary
      prevention cohort and 49.2% and 17.1% in the secondary intervention cohort. At
      the 6- and 12-month visits, a small adverse effect of intensive treatment was
      noted ("early worsening"), followed by a beneficial effect that increased in
      magnitude with time. Beyond 3.5 years of follow-up, the risk of progression was
      five or more times lower with intensive treatment than with conventional
      treatment. Once progression occurred, subsequent recovery was at least two times
      more likely with intensive treatment than with conventional treatment. Treatment
      effects were similar in all baseline retinopathy severity subgroups. CONCLUSIONS:
      The results of the Diabetes Control and Complications Trial strongly support the
      recommendation that most patients with insulin-dependent diabetes mellitus use
      intensive treatment, aiming for levels of glycemia as close to the nondiabetic
      range as is safely possible.

PMID- 7826294
TI  - Effects of aspirin on vitreous/preretinal hemorrhage in patients with diabetes
      mellitus. Early Treatment Diabetic Retinopathy Study report no. 20.
AB  - OBJECTIVE: To assess whether the use of aspirin exacerbates the severity or
      duration of vitreous/preretinal hemorrhages in patients with diabetic
      retinopathy. DESIGN: The Early Treatment Diabetic Retinopathy Study (ETDRS), a
      multicenter randomized clinical trial, was designed to assess the effect of
      photocoagulation and aspirin on 3711 patients with mild to severe
      nonproliferative or early proliferative diabetic retinopathy. INTERVENTION:
      Patients were randomly assigned to either an aspirin (650 mg/d) or a placebo
      group. One eye of each patient was randomly assigned to early photocoagulation
      and the other to deferral of photocoagulation. MAIN OUTCOME MEASURES: The
      severity and duration of the vitreous/preretinal hemorrhages were determined from
      gradings of the annual, seven standard stereoscopic field, fundus photographs.
      Clinical examinations scheduled every 4 months also provided information on the
      presence and duration of hemorrhages. RESULTS: Annual fundus photographs of eyes
      assigned to deferral of photocoagulation revealed vitreous/preretinal hemorrhages
      at some time during follow-up in 564 patients (30%) assigned to the placebo group
      and 585 patients (32%) assigned to the aspirin group (P = .48). Based on gradings
      of fundus photographs, there were no statistical differences in the severity of
      vitreous/preretinal hemorrhages (P = .11) or their rate of resolution (P = .86)
      between the groups. Clinical examination of eyes assigned to deferral of
      photocoagulation revealed 721 eyes (39%) assigned to the aspirin group and 689
      (37%) assigned to the placebo group that had vitreous/preretinal hemorrhages
      during the course of the study (P = .30). Again, no statistically significant
      difference was found between the rates of resolution, as assessed clinically,
      between the two treatment groups (P = .43). CONCLUSIONS: As previously reported,
      the use of aspirin did not increase the occurrence of vitreous/preretinal
      hemorrhages in patients enrolled in the ETDRS. The data presented in this report
      demonstrate that the severity and duration of these hemorrhages were not
      significantly affected by the use of aspirin and that there were no ocular
      contraindications to its use (650 mg/d) in persons with diabetes who require it
      for treatment of cardiovascular disease or for other medical indications.

PMID- 7826295
TI  - Surgical management of submacular hemorrhage. A series of 47 consecutive cases.
AB  - BACKGROUND: The development of a thick submacular hemorrhage usually carries a
      poor visual prognosis. The surgical removal of submacular blood may improve the
      otherwise poor outlook in these cases. SUBJECTS AND METHODS: Forty-seven
      consecutive patients underwent vitrectomy with surgical removal of submacular
      hemorrhage. The patient population consisted of two consecutive groups. Group 1
      (1989 to 1991) included 23 patients (20 with age-related macular degeneration
      [ARMD], one with idiopathic submacular hemorrhage, one with presumed ocular
      histoplasmosis syndrome [POHS], and one with angioid streaks) who underwent
      mechanical clot extraction. Group 2 (1991 to 1993) included 24 patients (19 with
      ARMD, two with POHS, two with arterial macroaneurysm, and one with angioid
      streaks) who underwent tissue plasminogen activator-assisted drainage of thick
      submacular hemorrhage. The dose of tissue plasminogen activator ranged from 10 to
      40 micrograms. All patients had surgery within 72 hours of diagnosis. RESULTS: In
      group 1, the mean size of the submacular hemorrhage was 11 disc areas (range, 1
      to 16 disc areas). Mean follow-up was 40 weeks. Mean postoperative visual acuity
      for eyes with ARMD was 20/200. (Visual acuity improved in six eyes, was stable in
      seven eyes, and deteriorated in seven eyes.) All three of the eyes without ARMD
      had visual improvement with a mean postoperative visual acuity of 20/70. Overall,
      visual acuity stabilized or improved in 13 (57%) of 23 patients and decreased in
      10 (43%) patients. In group 2, the mean size of the submacular hemorrhage was 11
      disc areas (range, 3 to 16 disc areas). Mean follow-up was 24 weeks. Mean
      postoperative visual acuity for eyes with ARMD was 20/480 (visual acuity was
      stable in 15 eyes, improved in two eyes, and deteriorated in two eyes). Four of
      five eyes without ARMD had visual improvement and one was stable, with a mean
      postoperative visual acuity of 20/60. Visual acuity stabilized or improved in 22
      (92%) of 24 patients and decreased in two (8%). The degree of clot lysis was
      variable. CONCLUSIONS: Submacular hemorrhage secondary to ARMD has a poor visual
      prognosis, with or without surgical drainage. The addition of tissue plasminogen
      activator-assisted clot lysis does not appear to significantly improve the visual
      outcome following surgery. The determination of whether surgical intervention is
      appropriate in these cases requires a prospective, randomized clinical trial.

PMID- 7826296
TI  - Short-wavelength automated perimetry in low-, medium-, and high-risk ocular
      hypertensive eyes. Initial baseline results.
AB  - OBJECTIVE: To examine the relationship between the prevalence of short-wavelength
      sensitivity losses in the central 30 degrees visual field and risk factors for
      development of glaucomatous visual field loss in ocular hypertension. DESIGN: A
      modified Humphrey Field Analyzer was used to perform standard automated perimetry
      and short-wavelength automated perimetry (SWAP), which is a technique that
      isolates the activity of short-wavelength-sensitive ("blue") mechanisms. In
      addition, an assessment of the risk of developing glaucomatous visual field loss
      was determined, based on a validated model that utilized intraocular pressure, a
      family history of glaucoma, age, and the vertical cup-to-disc ratio. PATIENTS:
      Both eyes of 232 ocular hypertensive patients were examined and compared with
      results from an age-matched control group of normal subjects. Both ocular
      hypertensive patients and normal subjects had to have normal visual fields on
      standard automated perimetry, good visual acuity, and no evidence of other ocular
      or neurologic disease or surgery. Intraocular pressure in the ocular hypertensive
      patients was 21 mm Hg or greater OU (without medication), and it was less than 20
      mm Hg OU in normal control subjects. RESULTS: Less than 10% of the low-risk
      ocular hypertensive eyes had a SWAP deficit, as compared with 20% of the moderate
      risk and 33% of the high-risk ocular hypertensive eyes. Intraocular pressure and
      a family history of glaucoma showed no meaningful relationship with the
      prevalence of SWAP deficits, but both age and the vertical cup-to-disc ratio
      demonstrated a strong association with the SWAP abnormalities. CONCLUSIONS: The
      SWAP results that were found in the ocular hypertensive eyes were associated with
      other risk factors that have been reported to be predictive of the development of
      glaucomatous visual field loss, especially the vertical cup-to-disc ratio and
      age. These findings support the notion that the SWAP deficits represent early
      glaucomatous damage and may be related to early changes that occur at the optic
      nerve head.

PMID- 7826297
TI  - The cardiovascular, pulmonary, and ocular hypotensive effects of 0.2%
      brimonidine.
AB  - OBJECTIVE: To compare the cardiovascular, pulmonary, and ocular hypotensive
      effects of 0.2% brimonidine tartrate with those of 0.5% timolol maleate, 0.25%
      betaxolol suspension, and brimonidine vehicle. DESIGN AND PATIENTS: A single
      center, double-masked, randomized, crossover study of 24 young, healthy men.
      INTERVENTIONS: Baseline heart rate, blood pressure, respiratory rate, and
      intraocular pressure were recorded at hour 0. At hour 2, heart rate, blood
      pressure, respiratory rate, and forced expiratory volume in 1 second were
      measured and a 15-minute treadmill test performed. Hour 0 measurements were
      repeated at hour 4. On four subsequent visits, we instilled one drop of a study
      medication into each eye after the baseline measurements at hour 0. RESULTS:
      Timolol reduced resting (-5.3 to -6.5 beats/min, P < or = .004) and exercise
      induced heart rate (-4.3 to -13.6 beats/min; P < or = .022) compared with
      brimonidine, betaxolol suspension, and brimonidine vehicle. At hour 4,
      brimonidine reduced resting systolic blood pressure compared with all other study
      medications (-5.2 to -7.3 mm Hg; P < or = .024). Timolol reduced systolic blood
      pressure during exercise and brimonidine reduced systolic blood pressure during
      recovery more than betaxolol suspension and brimonidine vehicle (-5.1 to -7.7 mm
      Hg; P < or = .033; and -5.4 to -6.0 mm Hg; P < or = .002, respectively). Mean
      respiratory rate and forced expiratory volume in 1 second were not significantly
      altered by any study medication. At hour 4, brimonidine lowered intraocular
      pressure as well as timolol and better than betaxolol suspension (-1.9 mm Hg; P <
      .001) or brimonidine vehicle (-1.8 mm Hg; P < .001). CONCLUSIONS: The
      cardiopulmonary effects of 0.2% brimonidine were limited to a slight reduction in
      systolic blood pressure during recovery from exercise and at 4 hours after
      instillation. The ocular hypotensive effect of brimonidine was comparable to that
      of timolol and greater than that of betaxolol suspension in this patient
      population.

PMID- 7826298
TI  - Tear function index. A new measure of dry eye.
AB  - OBJECTIVE: To develop an efficient way to evaluate tear dynamics clinically.
      PARTICIPANTS: Three hundred fifty-two patients with dry eye, 64 of whom had
      Sjogren syndrome, and 55 normal subjects. DESIGN: Because various forces that
      affect tear drainage are reflected in the values of the Schirmer test with
      anesthesia and the tear clearance rate, we introduced a new measure of tear
      dynamics, the tear function index, which is the value obtained from dividing the
      value of the Schirmer test with anesthesia by the tear clearance rate. RESULTS:
      The tear function index was more specific (91.8%) and sensitive (78.9%) in
      diagnosing dry eye associated with Sjogren syndrome than was the Schirmer or tear
      clearance rate test alone. Tear function indexes below 96 were consistent with
      dry eye and those below 34 were seen primarily in patients with Sjogren syndrome.
      CONCLUSIONS: The tear function index offers a new method to evaluate tear
      production with the Schirmer test, introduces an extended way to measure tear
      flow combining with tear drainage, and gives a practical measure to diagnose dry
      eye.

PMID- 7826299
TI  - The predictive value of cytomegalovirus retinitis for cytomegalovirus
      encephalitis in acquired immunodeficiency syndrome.
AB  - Cytomegalovirus (CMV) infection of the brain, optic nerves, and retinas from 47
      consecutive autopsies of patients with acquired immunodeficiency syndrome (AIDS)
      were examined. Immunocytochemistry demonstrated CMV infection in 11 (23%) brains,
      two (2%) of 94 optic nerves, and 38 (40%) of 94 retinas. Ten (91%) of 11 patients
      with CMV encephalitis had concurrent retinitis. While 10 (42%) of 24 patients
      with CMV retinitis had CMV encephalitis, when the retinitis included the
      peripapillary region, 75% had encephalitis. Usually, the optic nerve parenchyma
      was not infected histologically despite extensive peripapillary retinitis. The
      strength of these associations suggests that CMV retinitis defines a group of
      patients with AIDS at risk for development of CMV encephalitis (relative risk,
      9.5), particularly when the retinitis involves the peripapillary region (relative
      risk, 13). Furthermore, in patients with AIDS without CMV retinitis, central
      nervous system symptoms are unlikely to be attributable to CMV encephalitis.

PMID- 7826300
TI  - High-resolution magnetic resonance imaging evaluation of blood-retinal barrier
      integrity following transscleral diode laser treatment.
AB  - OBJECTIVE: To compare the effects of contact transscleral diode laser treatment
      and retinal cryotherapy on blood-retinal barrier integrity with the use of high
      resolution magnetic resonance imaging techniques with constant infusion of
      gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA). METHODS: Transscleral
      diode laser photocoagulation and retinal cryotherapy were used to treat
      equivalent areas of the inferior retinal periphery of pigmented rabbits. Magnetic
      resonance imaging time-course studies with measurement of signal enhancements due
      to Gd-DTPA leakage were conducted 2 and 15 days following treatment. RESULTS: Two
      days following treatment, cryotherapy-treated eyes exhibited a mean (+/- SD)
      effective Gd-DTPA permeability coefficient of 4.6 +/- 0.8 x 10(-6) cm/s; in
      comparison, diode laser-treated eyes exhibited 1.6 x 1.4 x 10(-6) cm/s effective
      permeability. Significant decreases in the effective permeability were also noted
      15 days after treatment in both groups. CONCLUSIONS: Transscleral contact probe
      diode laser photocoagulation induces less disruption of the blood-retinal barrier
      than does conventional cryotherapy. In addition, the continuous infusion method
      of Gd-DTPA delivery is a reliable and easily interpretable alternative to the
      commonly used bolus injection approach.

PMID- 7826301
TI  - A study of urinary dolichols as a biological marker for alcohol abuse. Report 2:
      Comparison of urinary dolichols/creatinine concentrations among non-drinkers,
      moderate-drinkers and heavy-drinkers.
AB  - We report here the comparison of urinary dolichols/creatine (D/Cr) concentration
      ratios in male non-drinkers, moderate-drinkers and heavy drinkers at admission
      and during hospitalization, and also discuss its usefulness as a biological
      marker for alcohol abuse. Urine samples were collected from the following four
      experimental groups: non-(male and female) and moderate-drinker (male)
      volunteers, and alcoholic heavy-drinking patients (male) at admission for
      psychiatric treatment and after 9-15 days hospitalization (informed consent was
      obtained). Urinary dolichols were determined by high performance liquid
      chromatography after BondElutC18 (500 mg) extraction. Due to significant
      differences in urinary D/Cr concentrations between male and female groups in non
      drinkers and because the heavy-drinkers available for this study were exclusively
      male, comparison of the value of urinary D/Cr concentration ratios was
      subsequently limited to male only. There were no statistical differences in
      urinary D/Cr concentrations in the male among non-drinkers, moderate-drinkers and
      heavy-drinkers at admission. The accuracy of urinary D/Cr as a biological marker
      for alcohol abuse, calculated using the mean +/- 2 s.d. in non- and moderate
      drinkers as the normal range, is only 33.3% in heavy-drinkers at admission, while
      their value of gamma-GTP in serum was 88.3%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7826302
TI  - [Effects of ethanol on isometric tonus of guinea pig gall bladder strips].
AB  - Using gall bladder strips isolated from guinea pigs, effects of ethanol treatment
      in vitro and in vivo on gall bladder tonus were studied. In the control (glucose
      administrated) group, the reactivity and sensitivity of ACh contraction of the
      strips were attenuated by ethanol at the concentration of 200 mM and over, while
      those of CCK contraction was attenuated at the concentration of 200 mM over. On
      the other hand, in the strips from guinea pigs chronically administered 3%
      ethanol, both ACh- and CCK-induced contractions were inhibited by the ethanol at
      the concentrations of 200 mM over. It is known that CCK and ACh are main humoral
      factors in situ which influence gall bladder tone, and physiologically attainable
      concentrations of ethanol are below 100 mM. Therefore, it is concluded that the
      physiological concentrations of ethanol unlikely affect the motility of gall
      bladder in vivo.

PMID- 7826303
TI  - [A study of relationships among solvent inhalation, personality and expectancy;
      especially on affinity to hallucination, sensation seeking and neurotic
      tendency].
AB  - 94 delinquents in two homes for resocialization were surveyed to elucidate the
      relationship among the status of volatile solvent inhalation, expectancy and
      personality. The subjects were classified into solvent-inhalation group and non
      solvent-inhalation group, and the former was divided into solvent dependence
      group and abuse group according to DSM-III-R. Each group was given personality
      tests; general health questionnaire (GHQ), sensation seeking scale (SSS), the
      vividness of visual imagery (VVIQ), test of visual imagery control (TVIC) and
      Yatabe-Guilford test (YG). In addition we investigated expectancy and mental
      symptoms caused by inhalation in it. The results are summarized as follows; 1.
      Inhalation group scored higher on SSS than non-inhalation group. 2. Compared with
      abuse group, dependence group presented with 1) higher GHQ score meaning neurotic
      tendency; 2) higher TVIC score meaning imagery-control-ability; 3) a higher
      incidence of day-dream and hallucination, especially egosyntonic type; 4) higher
      expectancy of "enhancement of positive affection", "reduction of negative
      affection" and "hallucination seeking"; 5) lower expectancy of "association with
      friends". 3. Higher scored inhalers on TVIC showed visual hallucinations,
      especially egosyntonic type more frequently than lower ones. 4. Significant
      correlations were recognized between GHQ score and expectancy of "reduction of
      negative affection", and between lack of objectiveness score of YG subscale and
      "hallucination seeking" expectancy. These results suggested that 1) beginning of
      inhalation is associated with sensation seeking trait, 2) progression to solvent
      dependence is correlated with three expectancies, i.e., seeking egosyntonic
      hallucinations paralleling high imagery-control-ability and subjectivity,
      reducing negative affection paralleling neurotic tendency, and enhancing positive
      affection. According to the findings, indulgence to drug induced positive imagery
      led delinquents into splitting of personality. In their treatment we need to help
      them to integrate high imagery ability and sensation seeking for recovery.

PMID- 7826304
TI  - Extracellular matrix arrangement in the papillary muscles of the adult rat heart.
      Alterations after doxorubicin administration and experimental hypertension.
AB  - In the present study, we analyzed the components of the extracellular matrix
      (ECM) and its arrangement at the level of the papillary muscles in the adult rat
      heart using light and transmission and scanning electron microscopy techniques.
      Our results reveal that after a single dose (6 mg/kg) of dexorubicin to cause a
      significant decrease and disorganization of the endomysium and perimysium in the
      first week after injection, affecting the endomysial struts and perimysial
      strands. Degenerating myocytes and alterations of the coiled perimysial fibers
      were characteristic 4 weeks after treatment. After 8 weeks, ultrastructural
      alterations at the level of the plasma membrane of the myocytes and adjacent
      collagen network were present in the tip of the papillary muscles. These
      alterations may be responsible for the inefficiency of the valvular apparatus as
      an initial factor implicated in doxorubicin-induced congestive heart failure.
      Experimental hypertension, produced by constriction of the abdominal aorta,
      induced hypertrophy of the left ventricle, with increased perimysium and
      endomysium of the ECM at the level of the papillary muscles 4 weeks after aortic
      banding. Interstitial and perivascular fibrosis were observed 8 weeks after
      surgical treatment, and macrophages around the degenerating myocytes were
      characteristic 16 weeks after treatment. These alterations of the ECM network
      have been correlated with their possible implication in ventricular biomechanical
      properties.

PMID- 7826305
TI  - Cellular and mitochondrial energy metabolism in the stunned myocardium.
AB  - The influence of cardiac stunning on the oxidation of fatty acids and the
      oxidative phosphorylation in mitochondria was investigated. Rat hearts were
      perfused for 15 min according to the working mode with a Krebs-Henseleit buffer
      containing glucose (11 mM). The hearts were then maintained in normoxic
      conditions (C group) or subjected to a 15-min global no-flow normothermic
      ischemia followed by a 30-min reperfusion (R group). Throughout the perfusion,
      the aortic and coronary flows, and the heart rate and oxygen consumption were
      monitored. At the end of the perfusion procedure, a bolus of 1-14C palmitate was
      injected in the coronary arterial bed to evaluate the fatty acid oxidation. Two
      sub-populations of mitochondria were isolated from each heart by either
      mechanical (ME mitochondria) or enzymic (EE mitochondria) extraction and their
      respiration properties were evaluated. Furthermore, the mitochondrial energy
      production (ATP and creatine phosphate) was assessed. During ischemia, the aortic
      flow was suppressed and recovered only to approximately 50% of the preischemic
      value during reperfusion. This mechanical stunning was associated with an
      important reduction of the stroke volume (-37%, p < 0.01) and a slight decrease
      in heart rate (-20%, p < 0.001). At the end of reperfusion, the beta-oxidation
      rate constituted 55 +/- 1.7% of the cell palmitate and was similar to that
      assessed in the C group. The oxygen consumption was decreased to 216 +/- 31.0
      microL O2/min/gww and the venous O2 concentration increased to 5.1 +/- 0.572
      microL O2/mL (instead of 2.9 +/- 0.342 microL O2/mL in the C group), although due
      to large SD, only the latter was statistically significant. A decrease in
      metabolic efficiency (42 +/- 14.4 vs 106 +/- 16.8 mL/microL O2 in the C group)
      and an increase in palmitate oxidation to oxygen consumption ratio (77 +/- 10.1
      vs 47.6 +/- 4.25% beta-oxidized palmitate/microL O2 in the C group) were
      observed. This increased fatty acid contribution in the oxidation metabolism
      could be responsible for some oxygen wasting and could contribute to decrease the
      energy available for the contraction despite the normal cardiac oxygen uptake.
      Furthermore, the respiration parameters of the mitochondria were similar in the C
      and R groups when glutamate (20 mM) or palmitoylcarnitine (25 microM) were used
      as substrate. ME mitochondria of R group displayed a reduced rate of ATP
      production (118 +/- 29.5 vs 180 +/- 14.5 nmoles/min/mg proteins in the C group)
      without altered creatine phosphate production. The presence of calcium in the
      medium (10(-5) M) provoked a decrease in ATP production.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 7826306
TI  - Release of adenine nucleotide metabolites by toxic concentrations of cardiac
      glycosides.
AB  - In isolated perfused guinea-pig hearts the effect of toxic concentrations of
      cardiac glycosides on the release of the adenine nucleotide metabolites
      adenosine, inosine, hypoxanthine, xanthine, and uric acid was investigated.
      Digoxin concentrations of 0.03-1 mumol.l-1 produced moderate to severe
      tachyarrhythmias. Large amounts of metabolites were released by concentrations of
      0.1 mumol.l-1, and higher. Occurrence of glycoside-induced ventricular
      fibrillation was associated with a particularly high release. Metabolite release
      was also obtained when fibrillation was elicited electrically in normal control
      hearts, or in hearts receiving simultaneously a marginally toxic digoxin
      concentration (0.03 mumol.l-1). Digoxin-induced tachyarrhythmias and metabolite
      release were almost completely prevented by a high potassium concentration in the
      coronary perfusion fluid (8.1 mmol.l-1). The antiarrhythmic effect was also
      obtained with lidocaine (60 mumol.l-1), but the release was only partially
      antagonized. Similar results concerning arrhythmias and metabolite release as
      with digoxin were obtained with ouabain. The findings suggest that the decrease
      in myocardial ATP observed in glycoside-intoxicated heart preparations is partly
      due to the loss of nucleotide precursor substances. Moreover, it appears likely
      that liberated adenosine in the interstitium of severely intoxicated heart
      preparations reaches pharmacologically effective concentrations.

PMID- 7826308
TI  - Transient effects of quick changes in myocardial metabolism and perfusion
      pressure on coronary vasomotor responses.
AB  - The effects of transient changes in coronary transmural pressure on the coronary
      vasomotor tone were studied in 23 anesthetized dogs. Increases and decreases of
      the coronary transmural pressure were obtained by constrictions of various
      duration (2 to 20 s) of the descending thoracic aorta. The maneuvers were
      performed in animals with intact cardiac innervation, with the vagi sectioned and
      with vagal section together with beta-blockade. In the absence of beta-blockade
      the increase in the transmural pressure caused a transient increase in the
      coronary vasomotor tone attributable to a myogenic contractile response and the
      extravascular compression. This contractile response was not observed when the
      transmural pressure was increased in the presence of high vasomotor tone after
      beta-blockade. In all animals a transient hyperemia was seen with its peak 8 to
      12 s after the release of the aortic constriction. Since its timing and amplitude
      were independent of the duration of the constriction, the metabolic effect of the
      increased ventricular afterload, although it may have contributed to the decrease
      of the coronary resistance, cannot be considered entirely responsible for the
      hyperemia, which was otherwise compatible with a myogenic vasodilatory response
      triggered by the sudden fall of the transmural pressure at the release of the
      constriction. It is concluded that, in the coronary circulation of the intact
      dog, transient changes in transmural pressure can induce vasomotor responses in
      which myogenic and metabolic mechanisms combine together in regulating the
      coronary flow. Changes in extravascular compression can also affect the flow when
      the experimental maneuver implies changes in the diastolic left ventricular
      pressure and volume. With the present experimental procedure the myogenic
      responses have been evidenced when the metabolic factors would have been expected
      to produce opposite changes in the vasomotor tone.

PMID- 7826307
TI  - Alteration of vascular endothelium and endothelium smooth muscle interaction
      after carbogen gas perfusion of isolated rat and guinea pig heart.
AB  - The aim of the study was to alter the vascular endothelium of the mammalian
      myocardium with respect to coronary flow regulation and vascular permeability.
      For this purpose, carbogen gas perfusion (GP) of Langendorff-type isolated rat
      and guinea pig heart was chosen. Perfusion of the hearts with carbogen gas was
      possible, as well as replacement of the GP by fluid perfusion. The energetic and
      mechanical state, the creatine kinase release, and the electron microscopic
      examination of the rat heart indicated only a moderate to minimal alteration of
      the cardiomyocytes after GP. As a result of GP a massive alteration of the
      vascular endothelium could be demonstrated in the rat heart, based on the release
      of the cytosolic endothelial marker enzyme, purine nucleoside phosphorylase, the
      partly altered vascular permeability and the morphologically detected endothelial
      damage to arterioles, capillaries and venules. Moreover, the reduced coronary
      flow response to short periods of anoxia (rat, guinea pig) and the inverted flow
      response to serotonin administration with maintained response to sodium
      nitroprusside (rat) in the post-gas perfusion period reflected an alteration of
      endothelial smooth muscular interaction in the rat and guinea pig heart.
      Furthermore, the distensibility of the coronary vasculature was increased in the
      rat and guinea pig heart in the post-gas perfusion period, where a relative
      autoregulatory behavior was maintained (rat) or partly maintained (guinea pig) in
      passively predilated vessels. In conclusion, carbogen gas perfusion of isolated
      hearts allows to induce preferred alteration of endothelium and endothelium
      smooth muscle interaction.

PMID- 7826309
TI  - Myocardial perfusion measured by dual-isotope acquisition of
      81rubidium/81mkrypton: an experimental verification of the method.
AB  - PURPOSE: The purpose of the study was to verify that the 81Rubidium/81mkrypton
      (81Rb/81mKr) method allows the quantitative measurement of myocardial perfusion.
      PRINCIPLE: The potassium analogous cation 81Rb is accumulated in the myocardium
      by the cell membrane-bound Na-K-ATPase. After accumulation an intracellular
      equilibrium establishes between 81Rb and its radioactive daughter nuclide 81mKr.
      The flow-sensitive method evaluates the disturbance of this equilibrium by
      perfusion which washes out the short-lived diffusable daughter nuclide 81mKr
      while the mother nuclide 81Rb remains cell-bound. METHODS: Isolated rabbit hearts
      were prepared in a modified Langendorff technique which allowed quantitative
      collection of the coronary sinus efflux. The myocardium was labeled with pure
      81Rb by bolus injection into the aortic cannula. Spectroscopic measurements of
      81Rb and 81mKr gamma radiation were performed using a germanium detector.
      Perfusion was varied in the range between 0 and 4 ml/min/g. The activity ratio
      81Rb/81mKr was determined and compared with coronary sinus effusion. RESULTS:
      81Rb/81mKr activity ratio was closely related (r = 0.98) to perfusion as
      described by the predicted equation Rb/Kr = (F/2.96 P) + 1. (Rb/Kr = activity
      ratio between 81Rb and 81mKr in the myocardium; F = myocardial perfusion
      (ml/min/g); P = partition coefficient (myocardium/perfusate) for Krypton gas).
      The constant P was found to be 1.14 +/- 0.06 (mean +/- SEM). No saturation of
      this ratio at high flow rates was observed. CONCLUSION: The activity ratio
      81Rb/81mKr is a valid quantitative measure for myocardial perfusion in isolated
      hearts. The main limitation of the method before application in man is the
      correction of the different gamma ray tissue absorption of both nuclides.

PMID- 7826310
TI  - Effect of magnesium administered during postischemic reperfusion on myocardial
      oxidative metabolism in isolated rat hearts.
AB  - To determine the effect of magnesium on myocardial function and oxidative
      metabolism after reperfusion, isolated rat hearts perfused retrogradely with
      erythrocyte-enriched medium (0.4 mM palmitate bound to 0.4 mM albumin, 11 mM
      glucose) were subjected to 60 minutes of no-flow ischemia followed by 60 minutes
      of reperfusion. Untreated postischemic hearts exhibited after 15 minutes of
      reperfusion recovery of myocardial oxygen consumption to 65% of the preischemic
      value despite persistent depression of left ventricular isovolumic pressure
      development to 21%. Magnesium (15 mM) administered during the initial 30 minutes
      of reperfusion reduced myocardial oxygen consumption of reperfuse myocardium by
      35%. Oxidation of [1-14C]palmitate was slightly more reduced (-55%) than
      oxidation of [U-14C]glucose (-42%). Magnesium did not influence ultimate recovery
      of contractile function and cumulative myocardial release of creatine kinase.
      Thus, 15 mM magnesium administered during reperfusion elicited a reduction of
      oxidative metabolism. However, magnesium did not modify myocardial injury.

PMID- 7826311
TI  - Isozyme patterns in callus cultures and in plants regenerated from calli of
      Cereus peruvianus (Cactaceae).
AB  - Electrophoretic patterns for isocitrate dehydrogenase (IDH; EC 1.1.1.42), acid
      phosphatase (ACP; EC 3.1.3.2), peroxidase (PER; EC 1.11.1.7), and esterase (EST;
      EC 3.1.1.1) isozymes were determined in Cereus peruvianus tissues and used as
      markers of genetic uniformity of calli and of the plants regenerated from callus
      cultures. One IDH, six ACP, six PER, and six EST isozymes were induced in
      cultured callus tissues in medium containing three 2,4-dichlorophenoxyacetic acid
      and kinetin combinations. Four ACP, two PER, and three EST isozymes were still
      present in all regenerated plants in vitro and therefore can be used as markers
      of the C. peruvianus plants regenerated from callus tissues. The differential
      patterns of ACP and IDH isozymes and the similar zymograms for PER and EST
      isozymes presented by callus tissues were used in a comparison of callus tissues
      cultured for 2 years. The comparative analysis of zymograms within each enzyme
      system indicated a mean heterogeneity coefficient of 0.33 for C. peruvianus calli
      cultured for 2 years. Because of the isozyme variations, which developed in
      culture medium and were transferred to the regenerated plants, the IDH, ACP, PER,
      and EST enzyme systems can be considered to be good markers for investigating
      possible genetic variations in plant populations of C. peruvianus obtained in
      vitro from callus culture.

PMID- 7826312
TI  - Paternity determination in the adder (Vipera berus)--DNA fingerprinting or random
      amplified polymorphic DNA?
AB  - We performed breeding experiments with adders (Vipera berus) to determine whether
      multiple matings may result in multiple paternity. DNA fingerprinting of mothers,
      their offspring, and possible fathers using a polydinucleotide probe [(TG)n] gave
      a low overall similarity between unrelated individuals (0.18 +/- 0.07; SD) and an
      average of 17 bands that were male-specific. In no cases were there fewer than
      seven paternal-specific bands present in the fingerprint of an offspring,
      enabling us unambiguously to identify the biological father among five males.
      Multiple paternity was detected in the investigated broods with offspring sired
      exclusively by the captive males. PCR amplification of random amplified
      polymorphic DNA (RAPD) using 16 decamer primers gave 76 bands and an average
      similarity of 0.95 (+/- 0.01) between the males, which were collected at
      different, geographically well-separated localities. Although there were on
      average 8.3 (+/- 1.9) bands that differ between males in pairwise comparisons,
      there were only 1.9 (+/- 1.1) bands per male that are specific for a particular
      individual. Thus, RAPDs are adequate for paternity determination only in
      experiments with a low number of males, whereas DNA fingerprinting offers
      sufficient information to discriminate between large numbers of putative fathers.

PMID- 7826313
TI  - Phylogenetic relationships among Homo sapiens and related species based on
      restriction site variations in rDNA spacers.
AB  - A rapid method, using 12 restriction enzymes, was employed to analyze variations
      in ribosomal DNA (rDNA) spacers in a study of phylogenetic relationships between
      Homo sapiens and related species. We mapped restriction sites in the external and
      internal spacer regions and compared the arrangements of sites. The estimated
      sequence divergence between Homo sapiens and Pan troglodytes, Pan paniscus,
      Gorilla gorilla, Pongo pygmaeus, Hylobates lar, H. agilis, and Macaca fuscata was
      2.7, 2.3, 3.8, 7.3, 6.8, 7.8, and 14.1%, respectively. The genetic relationships
      inferred from these distances generally correspond to those inferred from
      analyses of other molecular markers in the literature. The divergence between H.
      lar and H. agilis and between H. lar and H. syndactylus was 0.34 and 2.4%,
      respectively.

PMID- 7826314
TI  - The mouse salivary androgen-binding protein (ABP) alpha subunit closely resembles
      chain 1 of the cat allergen Fel dI.
AB  - Androgen-binding protein (ABP) is found in the salivas of a wide variety of
      rodents and it has been proposed that ABP functions in sex and/or subspecies
      recognition (Karn and Dlouhy, J. Hered. 82, 453, 1991). This is a report of
      significant identity between the alpha subunit of mouse salivary ABP and Chain 1
      of cat allergen Fel dI (50% identity), as well as with two other proteins that
      share identity with Chain 1 of Fel dI, rabbit uteroglobin (27% identity with ABP
      alpha) and human lung Clara 10 (27% identity with ABP alpha). The secondary
      structure predicted for the mouse ABP alpha subunit is a very good fit with the
      secondary structure determined by X-ray crystallography for rabbit uteroglobin, a
      protein that shares with mouse ABP the capability of binding steroid. Fel dI is
      found in cat saliva, sebaceous glands, and pelt. Its function is not known but it
      has been proposed to be involved in protecting dry epithelia, a parallel to
      uteroglobin protecting wet epithelia. Since mice, like cats, lick themselves and
      each other extensively, coating their pelts with ABP may be part of this or
      another biological function.

PMID- 7826315
TI  - The expression and anaerobic induction of alcohol dehydrogenase in cotton.
AB  - The alcohol dehydrogenase (ADH) system in cotton is characterized, with an
      emphasis on the cultivated allotetraploid species Gossypium hirsutum cv. Siokra.
      A high level of ADH activity is present in seed of Siokra but quickly declines
      during germination. When exposed to anaerobic stress the level of ADH activity
      can be induced several fold in both roots and shoots of seedlings. Unlike maize
      and Arabidopsis, ADH activity can be anaerobically induced in mature green
      leaves. Three major ADH isozymes were resolved in Siokra, and it is proposed that
      two genes, Adh1 and Adh2, are coding for these three isozymes. The genes are
      differentially expressed. ADH1 is predominant in seed and aerobically grown
      roots, while ADH2 is prominent in roots only after anaerobic stress. Biochemical
      analysis demonstrated that the ADH enzyme has a native molecular weight of
      approximately 81 kD and a subunit molecular weight of approximately 42 kD, thus
      establishing that ADH in cotton is able to form and is active as dimers.
      Comparisons of ADH activity levels and isozyme patterns between Siokra and other
      allotetraploid cottons showed that the ADH system is highly conserved among these
      varieties. In contrast, the diploid species of cotton all had unique isozyme
      patterns.

PMID- 7826316
TI  - Alterations in flightin phosphorylation in Drosophila flight muscles are
      associated with myofibrillar defects engendered by actin and myosin heavy-chain
      mutant alleles.
AB  - Flightin is a 20-kD myofibrillar protein found in the stretch-activated flight
      muscles of Drosophila melanogaster. Nine of the eleven isoelectric variants of
      flightin are generated in vivo by multiple phosphorylations. The accumulation of
      these isoelectric variants is affected differently by mutations that eliminate
      thick filaments or thin filaments. Mutations in the myosin heavy-chain gene that
      prevent thick filament assembly block accumulation of all flightin variants
      except N1, the unphosphorylated precursor, which is present at much reduced
      levels. Mutations in the flight muscle-specific actin gene that block actin
      synthesis and prevent thin filament assembly disrupt the temporal regulation of
      flightin phosphorylation, resulting in premature phosphorylation and premature
      accumulation of flightin phosphovariants. Cellular fractionation of fibers that
      are devoid of thin filaments show that flightin remains associated with the thick
      filament-rich cytomatrix. These results suggest that flightin is a structural
      component of the thick filaments whose regulated phosphorylation is dependent
      upon the presence of thin filaments.

PMID- 7826317
TI  - Adrenocorticotrophic-hormone-dependent regulation of a mu-class glutathione
      transferase in mouse adrenocortical cells.
AB  - Three different forms of glutathione transferase (GST) have been resolved in the
      two mouse adrenal tumour cell lines Y1 and Kin 8. Two of these belong to the mu
      and pi classes respectively. The third form is so far unidentified. In the Y1
      cells, the levels of the mu form (mGTmu1) and the unidentified form, are both
      down-regulated in the presence of adrenocorticotrophic hormone (ACTH) while the
      pi form is unaffected. The Kin 8 cell line is derived from Y1 cells and harbours
      a defect in the cyclic AMP (cAMP)-dependent protein kinase, making it refractory
      to cAMP-dependent regulation of several enzymes. The GST levels in this cell line
      were unaffected by ACTH. Also, the steady-state levels of mGTmu1 mRNA were much
      lower in Y1 cells treated with forskolin (which activates adenylate cyclase)
      compared with control cells, but there was no difference in mGTmu1 mRNA levels
      between control and forskolin-treated Kin 8 cells. This indicates that the ACTH
      dependent regulation of the mu class GST is pre-translational and that a
      functional cAMP-dependent protein kinase is required for the regulation. We have
      further shown that the difference in mRNA steady-state levels between control and
      forskolin-treated Y1 cells is abolished when transcription is inhibited by
      actinomycin D. In light of the stability of mGTmu1 mRNA, it would appear most
      likely that actinomycin D inhibits the transcription of short-lived factors which
      regulate the turn-over of mGTmu1 transcripts in response to changes in
      intracellular cAMP levels.

PMID- 7826318
TI  - Glucose-induced stimulation of human insulin-receptor mRNA and tyrosine kinase
      activity in cultured cells.
AB  - The effects of high glucose on insulin-receptor tyrosine kinase activity and gene
      expression were investigated in 3T3-HIR cells. Cells incubated for 48 h in the
      presence of 25 mM glucose showed a 5-fold increase in the amount of insulin
      receptors per cell, receptor autophosphorylation and phosphorylation of the
      exogenous substrate poly(Glu/Tyr) compared with cells grown in the absence of
      glucose but in the presence of 25 mM fructose. These effects were associated with
      a 4-fold stimulation in steady-state levels of insulin-receptor mRNA. Significant
      cellular glucose utilization and lactate production were observed in the presence
      of high glucose in the culture medium, indicating a functional glycolytic pathway
      in glucose-treated cells, but not in cells treated with fructose. Such a
      differential response to hexoses favours the hypothesis of a carbohydrate
      regulation via a glycolytic intermediate. This was further supported by a similar
      glucose-induced increase in mRNA levels of the enzyme glyceraldehyde-3-phosphate
      dehydrogenase. To test the hypothesis that the stimulatory effect of glucose on
      amount of insulin receptors and phosphorylation state could result from post
      transcriptional modifications, cells exposed to glucose were incubated with
      actinomycin D, a potent inhibitor of gene transcription. In cells challenged with
      high glucose plus inhibitor, insulin-receptor mRNA half-life was increased from 1
      to 3 h, indicating that posttranscriptional mechanisms are involved in these
      processes of glucose regulation. Inhibition of protein synthesis by cycloheximide
      induced an overexpression of insulin-receptor mRNA levels in the presence of
      glucose, suggesting that labile repressor protein(s) could be implicated in the
      effects of glucose. We conclude that (1) long-term culture with high glucose
      increases the amount of insulin receptors and their tyrosine kinase activity and
      (2) the glucose-induced increase in insulin-receptor mRNA levels can be accounted
      for, at least in part, by posttranscriptional events.

PMID- 7826319
TI  - Molecular cloning, expression and characterization of a ubiquitin conjugation
      enzyme (E2(17)kB) highly expressed in rat testis.
AB  - Ubiquitin-conjugating enzymes (E2s) play a key role in ubiquitin-mediated
      proteolysis by catalysing the conjugation of ubiquitin to protein substrates. We
      have previously reported the cDNA cloning of a 14 kDa conjugating enzyme
      [E2(14)k; Wing, Dumas and Banville (1992) J. Biol. Chem. 267, 6495-6501] that
      efficiently supported ubiquitination and protein degradation in reticulocyte
      extracts. Surprisingly, the structure of this E2 was markedly more similar to the
      Saccharomyces cerevisiae DNA repair gene RAD6, than to the S. cerevisiae
      UBC4/UBC5 genes which are required for the degradation of short-lived proteins
      and support much of the ubiquitination of yeast proteins. This suggested that
      mammalian homologues of UBC4/UBC5 remained to be identified. Using
      oligonucleotides derived from the S. cerevisiae UBC4 sequence as primers in a PCR
      reaction with rat muscle cDNA as a template, a 390 bp DNA fragment was amplified
      which predicted an amino acid sequence that was 83% identical to yeast UBC4.
      Screening a rat testes cDNA library identified a family of cDNAs which predicted
      two very similar proteins with basic pIs and molecular masses of approx. 16,700
      Da. Isoform 2E was expressed in Escherichia coli and purified to homogeneity. It
      supported ubiquitination to reticulocyte and testis proteins more rapidly in
      vitro and produced larger conjugates than E2(14)k. Examination of RNA from
      different tissues indicated that this type of E2 was expressed in a broad
      spectrum of tissues but at particularly high levels in the testis. Fractionation
      of a testis extract by anion-exchange chromatography identified several putative
      ubiquitin protein ligase activities with which this E2 could interact in
      promoting conjugation of ubiquitin to proteins. One of these activities supported
      conjugation of ubiquitin to histone H2A, a substrate degraded in the ubiquitin
      system by a non-N-end rule mechanism. This paper reports the first cloning of a
      apparent mammalian homologue of S. cerevisiae UBC4/UBC5. Its high expression in
      testis and ability to efficiently support conjugation to testis proteins suggest
      that this family of E2s may play a role in the proteolysis that occurs during
      spermatogenesis.

PMID- 7826320
TI  - Sinefungin shares AdoMet-uptake system to enter Leishmania donovani
      promastigotes.
AB  - The involvement of a carrier for sinefungin (SF) uptake in Leishmania donovani
      promastigotes is indicated by saturation kinetics, competition studies and SF
      accumulation against a 270-fold concentration gradient across the cell membrane.
      Whether SF uptake occurs via nucleoside- or AdoMet-carrier systems was
      investigated by competition experiments and comparison of the uptake of various
      molecules in wild-type and SF-resistant cells. Results show that SF did not
      inhibit purine or pyrimidine uptake whereas it competitively inhibited AdoMet
      uptake. Furthermore, the uptake of nucleosides in SF-resistant cells is similar
      to that in wild-type cells, whereas uptake of SF and AdoMet is lower.

PMID- 7826321
TI  - Purification and characterization of an Ins(1,3,4,5)P4 binding protein from pig
      platelets: possible identification of a novel non-neuronal Ins(1,3,4,5)P4
      receptor.
AB  - A novel Ins(1,3,4,5)P4-binding protein has been purified to apparent homogeneity
      from solubilized membranes derived from pig platelets. It has a high affinity for
      Ins(1,3,4,5)P4 (Kd 6.3 +/- 0.4 nM), a Bmax of 2.5-6.0 nmol/mg of protein, and a
      high specificity for Ins(1,3,4,5)P4 [Kd values for Ins(1,3,4,5,6)P5, InsP6,
      GroPtdIns(3,4,5)P3, Ins(1,4,5)P3, Ins(3,4,5,6)P4 and L-Ins(1,3,4,5)P4 of 85.0 +/-
      4.1 nM, 800.0 +/- 20.2 nM, 65.6 +/- 2.6 nM, > 10 microM, 793.3 +/- 55.6 nM and
      81.0 +/- 5.9 nM respectively]. The protein has an apparent molecular mass of 104
      kDa, suggesting that this peripheral tissue protein may be different from
      Ins(1,3,4,5)P4 binding proteins previously isolated from neuronal tissues.

PMID- 7826322
TI  - Characterization of a glutathione S-transferase and a related glutathione-binding
      protein from gill of the blue mussel, Mytilus edulis.
AB  - The major isoenzyme of glutathione S-transferase (GST 1) was purified to
      homogeneity from cytosolic extracts of Mytilus edulis gill tissue by GSH-agarose
      affinity chromatography followed by Mono Q ion-exchange f.p.l.c. This enzyme was
      particularly active with 1-chloro-2,4-dinitrobenzene, ethacrynic acid and cumene
      hydroperoxide as substrates. Immunoblotting and amino acid sequencing studies
      indicate that the enzyme belongs to the Pi class of GSTs. A related protein which
      binds to GSH-agarose was also purified. This GSH-binding protein did not
      immunoblot with GST antisera and showed no detectable catalytic activity with GST
      substrates although its N-terminal sequence was similar to Mu-class GSTs. Gel
      filtration chromatography indicated that GST 1 is a dimer and the GSH-binding
      protein a monomer. Mass spectrometry and SDS/PAGE indicate subunit molecular
      masses of 24 kDa (GST 1) and 25 kDa (GSH-binding protein), respectively. Both
      proteins have amino acid compositions typical of GSTs.

PMID- 7826323
TI  - Characterization of the two 5-aminolaevulinic acid binding sites, the A- and P
      sites, of 5-aminolaevulinic acid dehydratase from Escherichia coli.
AB  - Experiments are described in which the individual properties of the two 5
      aminolaevulinic acid (ALA) binding sites, the A-site and the P-site, of 5
      aminolaevulinic acid dehydratase (ALAD) have been investigated. The ALA binding
      affinity at the A-site is greatly enhanced (at least 10-fold) on the binding of
      the catalytic metal ion (bound at the alpha-site). The nature of the catalytic
      metal ion, Mg2+ or Zn2+, also gave major variations in the substrate Km, P-site
      affinity for ALA, the effect of potassium and phosphate ions and the pH
      dependence of substrate binding. Modification of the P-site by reaction of the
      enzyme-substrate Schiff base with NaBH4 and analysis of the reduced adduct by
      electro-spray mass spectrometry indicated a maximum of 1 mol of substrate
      incorporated/mol of subunit, correlating with a linear loss of enzyme activity.
      The reduced Schiff-base adduct was used to investigate substrate binding at the A
      site by using rate-of-dialysis analysis. The affinity for ALA at the A-site of Mg
      alpha Zn beta ALAD was found to determine the Km for the reaction and was pH
      dependent, with its affinity increasing from 1 mM at pH 6 to 70 microM at pH 8.5.
      The affinity of ALA at the P-site of Zn alpha An beta ALAD is proposed to limit
      the Km at pH values above 7, since the measured Kd for ALA at the A-site in 45
      microM Tris, pH 8, was well below the observed Km (600 microM) under the same
      conditions. The amino group of the ALA molecule bound at the P-site was
      identified as a critical binding component for the A-site, explaining why ALA
      binding to ALAD is ordered, with the P-site ALA binding first. Structural
      requirements for ALA binding at the A- and P-sites have been identified: the P
      site requires the carbonyl and carboxylate groups, whereas the A-site requires
      the amino, carbonyl and carboxylate groups of the substrate.

PMID- 7826324
TI  - Direct targeting of neutral endopeptidase (EC 3.4.24.11) to the apical cell
      surface of transfected LLC-PK1 cells and unpolarized secretion of its soluble
      form.
AB  - LLC-PK1 cells were transfected with a cDNA encoding rabbit neutral endopeptidase
      (NEP; EC 3.4.24.11), an abundant enzyme of the kidney proximal brush border.
      Clones of cells expressing high levels of the protein were isolated. Selective
      biotinylation and radioimmunolabelling were used to determine that 85-95% of NEP
      was localized in the apical domain of filter-grown LLC-PK1 cells. Pulse-chase and
      selective biotinylation studies revealed that the majority (85%) of newly made
      NEP was directly targeted to the apical membrane. However, a soluble form of NEP
      was found to be secreted in approximately equal amounts from both sides of the
      monolayer when expressed in LLC-PK1 cells. Transfected pro-opiomelanocortin, a
      pituitary hormone precursor, was secreted almost exclusively into the basolateral
      medium, suggesting that the bulk flow is to the basolateral membrane. This
      behaviour contrasts with that observed in MDCK cells, where both the
      transmembrane and secreted forms of NEP are directly targeted to the apical
      membrane and where the secretion of pro-opiomelanocortin is unpolarized.

PMID- 7826325
TI  - The effect of low temperatures on enzyme activity.
AB  - The stability of two enzymes from extreme thermophiles (glutamate dehydrogenase
      from Thermococcales strain AN1 and beta-glucosidase from Caldocellum
      saccharolyticum expressed in Escherichia coli) has been exploited to allow
      measurement of activity over a 175 degrees C temperature range, from +90 degrees
      C to -85 degrees C for the glutamate dehydrogenase and from +90 degrees C to -70
      degrees C for the beta-glucosidase. The Arrhenius plots of these enzymes, and
      those for two mesophilic enzymes (glutamate dehydrogenase from bovine liver and
      beta-galactosidase from Escherichia coli), exhibit no downward deflection
      corresponding to the glass transition, found by biophysical measurements of
      several non-enzymic mesophilic proteins at about -65 degrees C and reflecting a
      sharp decrease in protein flexibility as the overall motion of groups of atoms
      ceases.

PMID- 7826326
TI  - Human kininogens interact with M protein, a bacterial surface protein and
      virulence determinant.
AB  - Streptococcus pyogenes, the most significant streptococcal species in clinical
      medicine, expresses surface proteins with affinity for several human plasma
      proteins. Here we report that kininogens, the precursors to the vasoactive
      kinins, bind to the surface of S. pyogenes. M protein, a surface molecule and a
      major virulence factor-in these bacteria, occurs in > 80 different serotypes.
      Among 49 strains of S. pyogenes, all of different M serotypes, 41 bound
      radiolabelled kininogens, whereas 6 M protein-negative mutant strains showed no
      affinity. M protein of most serotypes bind fibrinogen, and among the 55 strains
      tested, binding of kininogens was closely correlated to fibrinogen binding (r =
      0.88, P < 0.0001). Western blotting, slot binding and enzyme immunoassay
      experiments demonstrated that M proteins isolated from S. pyogenes of three
      different M protein serotypes (M1, M6 and M46) bound kininogens. The affinity
      between kininogens and M1 protein was determined to be 5 x 10(7) M-1 and < or =
      10(6) M-1 for high molecular weight (H-kininogen) and low molecular weight
      kininogen, respectively. The kininogen binding site was tentatively mapped to the
      N-terminal portion of M1 protein, and this site does not overlap the specific and
      separate binding sites for albumin, IgG and fibrinogen using monoclonal
      antibodies to, and synthetic peptides of, the kininogen sequence, the major M
      protein-binding site(s) was mapped to the C-terminal portion of the H-kininogen
      light chain. We anticipate that the kininogen-M protein interaction contributes
      to the host-parasite relationship in S. pyogenes infections.

PMID- 7826327
TI  - Effects of quin2 acetoxymethyl ester on H2O2-induced DNA single-strand breakage
      in mammalian cells: H2O2-concentration-dependent inhibition of damage and
      additive protective effect with the hydroxyl-radical scavenger dimethyl
      sulphoxide.
AB  - The cell-membrane-permeable calcium probe quin2 acetoxymethyl ester (quin2 AM)
      was ineffective, in comparison with o-phenanthroline, in protecting cells against
      H2O2-induced DNA single-strand breakage at H2O2 concentrations of about, and
      higher than, 0.5 mM. The present study shows that quin2 actually potentiated
      intracellular DNA damage at high H2O2 concentrations. H2O2-induced DNA breakage
      appeared within 5 min after exposure, and quin2 affected the induction of DNA
      breaks at both 0 degree C and 37 degrees C. Aurintricarboxylic acid, an
      endonuclease inhibitor, or a decrease in extracellular Ca2+, did not reduce DNA
      damage. These facts strongly suggest that the breaks were not produced by a
      Ca(2+)-dependent nuclease. We showed previously that, in the presence of Fe3+ and
      H2O2, quin2 strongly potentiated the formation of oxidizing species as well as
      plasmid DNA breakage, and, as could be expected for a transition-metal chelator,
      quin2 inhibited the Fenton reaction when Cu2+ was tested instead of Fe3+
      [Sandstrom, Granstrom and Marklund (1994) Free Radicals Biol. Med. 16, 177-185].
      In the present work with cultured cells, titration with quin2 AM showed that,
      despite the fact that Cu2+ has a three-to-four-orders-of-magnitude higher
      affinity for quin2 than has Fe3+, both inhibition and potentiation of H2O2
      induced DNA damage occurred at quin2 AM concentrations of about 100 nM. Thus
      inhibition appeared not to involve Cu2+. The combination of quin2 AM and dimethyl
      sulphoxide (DMSO) gave an additive effect on H2O2-induced DNA damage compared
      with the effect of quin2 AM or DMSO alone, whereas the combination of o
      phenanthroline and DMSO gave about the same effect as o-phenanthroline alone. In
      conclusion, our results do not support a role for Ca2+ in the inhibiting effect
      of quin2 on H2O2-induced DNA damage. Instead, it is likely that inhibition and
      potentiation by quin2 involves interaction with Fe ions.

PMID- 7826328
TI  - Isolation, purification and structure of exochelin MS, the extracellular
      siderophore from Mycobacterium smegmatis.
AB  - The extracellular siderophore from Mycobacterium smegmatis, exochelin MS, was
      isolated from iron-deficiently grown cultures and purified to > 98% by a
      combination of ion-exchange chromatography and h.p.l.c. The material is
      unextractable into organic solvents, is basic (pI = 9.3-9.5), has a lambda max at
      420 nm and a probable Ks for Fe3+ of between 10(25) and 10(30). Its structure has
      been determined by examination of desferri- and ferri-exochelin and its gallium
      complex. The methods used were electrospray-m.s. and one- and two-dimensional
      (NOESY, DQF-COSY and TOCSY) 1H n.m.r. The constituent amino acids were examined
      by chiral g.l.c analysis of N-trifluoroacetyl isopropyl and N
      pentafluoropropionyl methyl esters after hydrolysis, and reductive HI hydrolysis,
      of the siderophore. The exochelin is a formylated pentapeptide: N-(delta-N
      formyl,delta N-hydroxy-R-ornithyl) -beta-alaninyl-delta N-hydroxy-R-ornithinyl-R
      allo-threoninyl-delta N-hydroxy-S-ornithine. The linkages involving the three
      ornithine residues are via their delta N(OH) and alpha-CO groups leaving three
      free alpha-NH2 groups. Although there are two peptide bonds, these involve the
      three R (D)-amino acids. Thus the molecule has no conventional peptide bond, and
      this suggests that it will be resistant to peptidase hydrolysis. The co
      ordination centre with Fe3+ is hexadenate in an octahedral structure involving
      the three hydroxamic acid groups. Molecular modelling shows it to have similar
      features to other ferric trihydroxamate siderophores whose three-dimensional
      structures have been established. The molecule is shown to have little
      flexibility around the iron chelation centre, although the terminal (Orn-3)
      residue, which is not involved in iron binding except at its delta N atom, has
      more motional freedom.

PMID- 7826329
TI  - Chemical modifications of a recombinant bovine stress-inducible 70 kDa heat-shock
      protein (Hsp70) mimics Hsp70 isoforms from tissues.
AB  - A cDNA clone for the stress-inducible 70 kDa heat-shock protein (Hsp70) has been
      isolated from a bovine skeletal-muscle cDNA library. This mRNA encodes a protein
      with a calculated molecular mass of 70250 Da. The cDNA has one continuous open
      reading frame capable of encoding a 641-amino-acid protein. Expression of this
      cDNA in a bacterial expression system produced a protein with a mobility
      identical with that of the inducible Hsp70 protein from bovine skeletal muscle as
      determined by SDS/PAGE. Two-dimensional gel electrophoresis demonstrated this
      protein to have focusing properties identical with that of a minor isoform from
      bovine skeletal muscle. Upon carbamylation of this bacterially expressed protein,
      a train of charged proteins with charge differences of -1 were produced. These
      carbamylated proteins were shown to have similar focusing mobilities to the Hsp70
      isoforms isolated from bovine skeletal muscle. These results demonstrate the
      identification of a skeletal-muscle inducible Hsp70 gene and suggest that the
      presence of multiple Hsp70 isoforms may be the product of post-translational
      modifications to the Hsp70 proteins.

PMID- 7826330
TI  - Characterization of a winged bean (Psophocarpus tetragonolobus) protein kinase
      with calmodulin-like domain: regulation by autophosphorylation.
AB  - A soluble protein kinase purified from winged bean (Psophocarpus tetragonolobus)
      shoots, has been assessed as a monomeric enzyme with an approximate M(r) of
      60,000 in spite of the presence of two polypeptides of 61 and 58 kDa determined
      by SDS/PAGE. Immunoblot analyses using either of the two antisera raised
      individually against the polypeptides, detect both of them in purified
      preparations and a single larger polypeptide (62 kDa) in freshly prepared tissue
      homogenates, clearly indicating the likelihood of the doublet being formed from
      the larger one by proteolysis. Histone H1, syntide 2 and a synthetic myosin light
      chain-related peptide (MLC-peptide) have been identified as exogenous substrates
      of the enzyme. Complete Ca(2+)-dependence for substrate phosphorylation, a
      drastic inhibition of the reaction by a calmodulin (CaM) antagonist which can be
      partially reversed by a heterologous CaM and direct 45Ca(2+)-binding on blot,
      form compelling evidence in favour of a CaM-like domain of the enzyme. Both the
      polypeptides of the purified enzyme undergo intramolecular autophosphorylation on
      serine residue(s). Unlike the substrate phosphorylation reaction,
      autophosphorylation is Ca(2+)-independent and is not inhibited by the CaM
      antagonist. Down-regulation of substrate phosphorylation by auto-phosphorylation,
      and stimulation of the autophosphorylation by histone H1 and MLC-peptide, are
      novel regulatory features of the enzyme.

PMID- 7826331
TI  - Ferritin does not accumulate iron oxidized by caeruloplasmin.
AB  - Ferritin is an iron-storage protein ubiquitous in mammals, plants and bacteria.
      It can be reconstituted, in vitro, from the apoprotein and Fe(II) salts in the
      presence of dissolved oxygen. Recently it has been reported that caeruloplasmin
      can facilitate apoferritin reconstitution and that iron oxidized by
      caeruloplasmin is sequestered within the ferritin shell. Here we show that the
      primary effect of adding caeruloplasmin to horse spleen ferritin during
      reconstitution is the competition between the two molecules for the iron. This
      competition results in overall increased rates of iron oxidation and a mixture of
      products, namely iron-containing ferritin and iron hydroxy polymers attached to
      caeruloplasmin. Iron oxidized by caeruloplasmin is not incorporated, to any
      significant extent, into horse spleen ferritin.

PMID- 7826332
TI  - Characterization of the human mucin gene MUC5AC: a consensus cysteine-rich domain
      for 11p15 mucin genes?
AB  - To date five human mucin cDNAs (MUC2, 5A, 5B, 5C and 6) mapped to 11p15.3-15.5,
      so it appears that this chromosome region might contain several distinct gene
      loci for mucins. Three of these cDNAs, MUC5A, B and C, were cloned in our
      laboratory and previously published. A common number, 5, was recommended by the
      Human Gene Mapping Nomenclature Committee to designate them because of their
      common provenance from human tracheobronchial mucosa. In order to define whether
      they are products of the same gene locus or distinct loci, we describe in this
      paper physical mapping of these cDNAs using the strategy of analysis of CpG
      islands by pulse-field gel electrophoresis. The data suggest that MUC5A and MUC5C
      are part of the same gene (called MUC5AC) which is distinct from MUC5B. In the
      second part of this work, complete sequences of the inserts corresponding to
      previously described (JER47, JER58) and novel (JER62, JUL32, MAR2, MAR10 and
      MAR11) cDNAs of the so-called MUC5AC gene are presented and analysed. The data
      show that in this mucin gene, the tandem repeat domain is interrupted several
      times with a subdomain encoding a 130 amino acid cysteine-rich peptide in which
      the TR3A and TR3B peptides previously isolated by Rose et al. [Rose, Kaufman and
      Martin (1989) J. Biol. Chem., 264, 8193-8199] from airway mucins are found. A
      consensus peptide sequence for these subdomains involving invariant positions of
      most of the cysteines is proposed. The consensus nucleotide sequence of this
      subdomain is also found in the MUC2 gene and in the MUC5B gene, two other mucin
      genes mapped to 11p15. The functional significance for secreted mucins of these
      cysteine-rich subdomains and the modular organization of mucin peptides are
      discussed.

PMID- 7826333
TI  - Effects of K+ on the binding of Ca2+ to the Ca(2+)-ATPase of sarcoplasmic
      reticulum.
AB  - Equilibrium and kinetic fluorescence methods have been used to characterize the
      interactions between K+ and the Ca(2+)-ATPase of skeletal-muscle sarcoplasmic
      reticulum. K+ shifts the E2-E1 equilibrium of the ATPase towards E1 and increases
      the rate of Ca2+ binding to the ATPase, as detected by changes in tryptophan
      fluorescence intensity, suggesting that K+ increases the rate of the E2-E1
      transition. The data are consistent with binding of K+ at the inner Ca(2+)
      binding site on the ATPase in competition with H+ and Mg2+, with a higher
      affinity in the E1 than in the E2 conformation. K+ has no effect on the affinity
      for Mg2+, as detected by changes in tryptophan fluorescence intensity; since it
      has been proposed that the changes in tryptophan fluorescence follow from binding
      to Mg2+ at the outer Ca(2+)-binding site, this suggests that K+ is unable to bind
      at the outer Ca(2+)-binding site. K+ increases the rate of dissociation of Ca2+
      from the Ca(2+)-bound ATPase and reduces the effect of Mg2+ on the fluorescence
      intensity of the ATPase labelled with 4-(bromomethyl)-6,7-dimethoxycoumarin. It
      is suggested that these effects of K+ are the result of binding at a 'gating'
      site on the ATPase, in competition with binding of H+. Binding of K+ at the inner
      Ca(2+)-binding site and at the gating site account for the observed effects of K+
      on the affinity of the ATPase for Ca2+.

PMID- 7826334
TI  - Polyamines in chloroplasts: identification of their glutamyl and acetyl
      derivatives.
AB  - Incubation of chloroplasts of Helianthus tuberosus with labelled putrescine
      and/or spermidine and proteolytic digestion of their trichloroacetate-soluble and
      -insoluble proteins revealed the presence of N-(gamma-glutamyl)-putrescine, N1,N4
      bis-(gamma-glutamyl)-putrescine and N1,N8-bis-(gamma-glutamyl)spermidine. This
      finding may be regarded as unequivocal proof of the presence of transglutaminase
      activity in chloroplasts. In addition, the recovery of spermidine or putrescine
      and acetylspermidine from chloroplasts incubated with [3H]putrescine or
      [3H]spermidine respectively indicates the existence of biosynthetic and oxidative
      pathways. These results suggest that polyamines may have an important function in
      chloroplasts both in their free form and by covalently binding to proteins.

PMID- 7826335
TI  - Site-directed mutagenesis of cysteine-195 in isocitrate lyase from Escherichia
      coli ML308.
AB  - Cysteine-195 was previously identified as a probable active site residue in
      isocitrate lyase (ICL) from Escherichia coli ML308 [Nimmo, Douglas, Kleanthous,
      Campbell and MacKintosh (1989) Biochem. J. 261, 431-435]. This residue was
      replaced with serine and alanine residues by site-directed mutagenesis. The
      mutated genes expressed proteins with low but finite ICL activity, which co
      migrated with wild-type ICL on both SDS/ and native PAGE. The mutant proteins
      were purified and characterized. Fluorimetry and c.d. in both the near- and the
      far-u.v. regions showed no differences between the mutants and wild-type ICL,
      indicating that the conformations of the three enzymes were very similar. ICL
      C195A (Cys-195-->Ala) and C195S (Cys-195-->Ser) showed 8.4-fold and 3.6-fold
      increases in the Km for isocitrate, while their kcat. values showed 30- and 100
      fold decreases respectively. The effect of pH on the kinetic properties of the
      wild-type and mutant ICLs was investigated. The results showed that the response
      of the mutant enzymes to pH was simpler than that of the wild-type. For the
      mutants, ionisation of a group with a pKa of approx. 7.8 affected the Km for
      isocitrate and kcat.. For the wild-type enzyme, these parameters were affected by
      the ionization of two or more groups, one of which is presumed to by cysteine
      195. The results are consistent with the view that the previously identified
      group with a pKa of 7.1 whose ionization affects the reaction of ICL by
      iodoacetate is cysteine-195 itself.

PMID- 7826336
TI  - Human proteasomes analysed with monoclonal antibodies.
AB  - The proteasome or multicatalytic endopeptidase from eukaryotic cells consists of
      at least 14 subunits that fall into two families, alpha and beta. Subunit
      specific monoclonal antibodies against ten different subunits of human
      proteasomes have been produced, together with an antibody that reacts with a
      motif (prosbox 1), common to alpha-type subunits. Four of the subunit-specific
      antibodies were able to precipitate proteasomes. The subunit composition of HeLa
      cell proteasomes precipitated with these four different antibodies were
      identical, as judged from two-dimensional electrophoresis. One of the four
      antibodies was used to obtain proteasomes from cell lines (HeLa, Daudi, IMR90 and
      BSC-1) and human tissues (placenta, kidney, and liver). Electrophoretic analysis
      of these proteasomes, combined with peptide mapping of some subunits, suggests
      that they all contain 14 types of subunits as their major constituents. However,
      one subunit was present in two isoelectric isoforms in all cells examined. Two
      other subunits occurred in two or three isoelectric isoforms in placenta, liver
      and kidney, but not in the cell cultures. Extracts of human cells (HeLa, IMR90,
      Daudi and erythrocytes) were analysed by non-denaturing electrophoresis and
      immunoblotting. All of the 11 subunits detected by antibodies were present in a
      pair of ATP-stabilized protein complexes, presumed to be the 26 S proteinase, and
      in a doublet of complexes which migrated more slowly than purified proteasomes.
      Besides being present in proteasomes, one subunit was also found to occur in the
      free state in cell extracts.

PMID- 7826338
TI  - Purification and characterization of recombinant pea-seed ferritins expressed in
      Escherichia coli: influence of N-terminus deletions on protein solubility and
      core formation in vitro.
AB  - Plant ferritin subunits are synthesized as precursor molecules; the transit
      peptide (TP) in their NH2 extremity, responsible for plastid targeting, is
      cleaved during translocation to this compartment. In addition, the N-terminus of
      the mature subunit contains a plant-specific sequence named extension peptide
      (EP) [Ragland, Briat, Gagnon, Laulhere, Massenet, and Theil, E.C. (1990) J. Biol.
      Chem. 265, 18339-18344], the function of which is unknown. A novel pea-seed
      ferritin cDNA, with a consensus ferroxidase centre conserved within H-type animal
      ferritins has been characterized. This pea-seed ferritin cDNA has been engineered
      using oligonucleotide-directed mutagenesis to produce DNA fragments (1)
      corresponding to the wild-type (WT) ferritin precursor, (2) with the TP deleted,
      (3) with both the TP and the plant specific EP sequences deleted and (4)
      containing the TP but with the EP deleted. These four DNA fragments have been
      cloned in an Escherichia coli expression vector to produce the corresponding
      recombinant pea-seed ferritins. Expression at 37 degrees C led to the
      accumulation of recombinant pea-seed ferritins in inclusion bodies, whatever the
      construct introduced in E. coli. Expression at 25 degrees C in the presence of
      sorbitol and betaine allowed soluble proteins to accumulate when constructs with
      the TP deleted were used; under this condition, E. coli cells transformed with
      constructs containing the TP were unable to accumulate recombinant protein.
      Recombinant ferritins purified from inclusion bodies were found to be assembled
      only when the TP was deleted; however assembled ferritin under this condition had
      a ferroxidase activity undetectable at acid pH. On the other hand, soluble
      recombinant ferritins with the TP deleted and expressed at 25 degrees C were
      purified as 24-mers containing an average of 40-50 iron atoms per molecule.
      Despite the conservation in the plant ferritin subunit of a consensus ferroxidase
      centre, the iron uptake activity in vitro at pH 6.8 was found to be lower than
      that of the recombinant human H-ferritin, though it was much more active than the
      recombinant human L-ferritin. The recombinant ferritin with both the TP and the
      EP deleted (r delta TP/EP) assembled correctly as a 24-mer; it has slightly
      higher ferroxidase activity and decreased solubility compared with the wild-type
      protein with the TP deleted (r delta TP). In addition, on denaturation by urea
      followed by renaturation by dialysis the r delta TP/EP protein showed a 25%
      increase in core-formation in vitro compared with the r delta TP
      protein.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7826337
TI  - Insulin stimulation of glycogen synthesis and glycogen synthase activity is
      blocked by wortmannin and rapamycin in 3T3-L1 adipocytes: evidence for the
      involvement of phosphoinositide 3-kinase and p70 ribosomal protein-S6 kinase.
AB  - We have investigated the involvement of phosphoinositide (PI) 3-kinase and p70
      ribosomal protein-S6 kinase (p70s6k) in mediating insulin stimulation of glycogen
      synthesis in 3T3-L1 adipocytes using specific inhibitors. Wortmannin inhibited PI
      3-kinase activity (IC50 approximately 10 nM), inhibition being complete at 100
      nm. Wortmannin (100 nM) completely blocked the ability of insulin to activate
      glycogen synthase in 3T3-L1 adipocytes and the ability of insulin to stimulate
      glucose incorporation into glycogen in 3T3-L1 fibroblasts. Rapamycin, which
      blocks insulin-stimulated activation of p70s6k, decreased insulin activation of
      glycogen synthase in a dose-dependent manner (IC50 approximately 0.8 ng/ml), with
      a maximum approx. 75% inhibition of insulin's stimulatory effect. Rapamycin
      inhibited insulin-stimulated glucose incorporation into glycogen to a similar
      extent and with similar dose-dependency, while having no effect on insulin
      stimulated glucose transport. We conclude that PI 3-kinase and p70s6k are
      involved in the signalling pathways by which insulin stimulates glycogen synthase
      in 3T3-L1 adipocytes.

PMID- 7826339
TI  - Distribution of albumin, alpha 1-inhibitor 3 and their respective mRNAs in
      periportal and perivenous rat hepatocytes isolated by the digitonin-collagenase
      technique.
AB  - The expression of albumin and alpha 1-inhibitor 3 genes was investigated in rat
      cell suspensions enriched in periportal (n = 10) and perivenous (n = 10)
      hepatocytes obtained by the digitonin-collagenase technique. The degree of
      enrichment of the cell suspensions was assessed: (1) by enzymic assays for the
      periportal marker alanine aminotransferase and for the perivenous marker
      glutamine synthetase; and (2) by their content of mRNAs for the periportal marker
      hepatic glutaminase and for glutamine synthetase. The existence of an antegrade
      intra-lobular gradient for albumin and alpha 1-inhibitor 3 mRNAs was
      demonstrated, with periportal:perivenous ratios of 2.33 and 3.80, respectively.
      However, no gradient was demonstrated for the respective protein contents with
      corresponding ratios of 0.98 and 1.21. A certain degree of overlap existed
      between periportal and perivenous suspensions for their content in albumin and
      alpha 1-inhibitor 3 mRNAs. A morphometrical analysis of the surface of digitonin
      permeabilized hepatic tissue revealed that this overlap could be explained by a
      variable extent of permeabilization of the mediolobular zone from one rat to
      another and from one lobule to another in a given animal. These results suggest
      that while the digitonin-collagenase technique is well suited for studies in
      vitro of proteins expressed in sharp intra-lobular gradients or restricted to an
      intra-lobular compartment, it is not completely reliable for proteins distributed
      in continuous moderate intra-lobular gradients, such as albumin and alpha 1
      inhibitor 3.

PMID- 7826340
TI  - Localization of non-conventional protein kinase C isoforms in bovine brain cell
      nuclei.
AB  - Using Western blotting and immunofluorescence microscopy we detected the protein
      kinase C isoforms delta, epsilon and zeta in isolated cell nuclei from bovine
      cerebral cortex. Both protein kinase C (PKC) delta and PKC epsilon are present in
      higher concentrations in neuronal than in glial nuclei and are located inside the
      nucleus and at the nuclear envelope. There they give a punctate staining in
      immunofluorescence microscopy. PKC zeta is also present both in the nucleoplasm
      and at the nuclear envelope. PKC eta could not be detected in the cell nuclei
      and, even in the homogenate of cerebral cortex, this isoform is present only in
      very low concentrations. The antibody against PKC eta bound strongly to a
      nucleoplasmic protein with an apparent molecular mass of 99 kDa. The localization
      of non-conventional PKC isoforms at the cell nucleus strongly indicates that
      these isoforms are directly involved in the regulation of nuclear processes.

PMID- 7826341
TI  - Immunological recognition of different forms of the neurotensin receptor in
      transfected cells and rat brain.
AB  - In this work, the molecular forms of the rat neurotensin receptor (NTR) expressed
      in transfected Chinese hamster ovary (CHO) cells, in infected Sf9 insect cells
      and in rat cerebral cortex were immunologically detected by means of an anti
      peptide antibody raised against a fragment of the third intracellular loop of the
      receptor. Immunoblot experiments against a fusion protein indicated that the anti
      peptide antibody recognized, under denaturing conditions, the corresponding amino
      acid sequence within the NTR. In immunoblot analysis of membranes from NTR
      transfected CHO cells, high levels of immunoreactivity were observed between 60
      and 72 kDa, while only a faint labelling was observed at 47 kDa, the molecular
      mass deduced for the rat NTR cDNA. The bands of high molecular mass were no
      longer observed after deglycosylation of membrane proteins by peptide N
      glycosidase F, indicating that they represented glycosylated forms of the
      receptor. Extracts of membranes derived from baculovirus-infected Sf9 insect
      cells expressing the NTR provided a quite different immunoblot pattern, since the
      major band detected in that case was at 47 kDa, the molecular size of the non
      glycosylated receptor. Taken together, these data show that, while most of the
      NTR protein was glycosylated in CHO cells, it was unglycosylated in Sf9 insect
      cells. In addition, molecular sizes of the receptor proteins observed in these
      two cell lines differed from those obtained for the NTR endogenously expressed in
      the rat cerebral cortex of 7 day-old rats, where bands at 56 and 54 kDa were
      detected. Binding experiments carried out on membrane preparations obtained from
      baculovirus-infected Sf9 cells demonstrated that the immunogenic sequence was
      still accessible to the antibody when the receptor was embedded in the cell
      membrane. Immunohistochemical studies carried out on both transfected CHO cells
      and infected Sf9 cells confirmed this interpretation and further indicated that
      the antibody could be applied in the visualization of the receptor.

PMID- 7826342
TI  - Changes in calcium influx affect the differentiation of murine erythroleukaemia
      cells.
AB  - As indicated by direct evidence, obtained by altering the cell-membrane
      permeability for Ca2+ in murine erythroleukaemia (MEL) cells, calpain is the
      triggering factor which connects fluctuations of the intracellular Ca2+
      concentrations to the decay of protein kinase C (PKC), as well as to the kinetics
      of cell differentiation induced by hexamethylenebisacetamide. Cell exposure to
      verapamil caused a profound decrease in the rate of PKC down-regulation and a
      slower initial rate of accumulation of mature erythroid cells, whereas addition
      of the Ca2+ ionophore A23187 produced opposite effects. The high susceptibility
      of PKC-delta to calpain degradation, at concentrations of Ca2+ much lower than
      those required for degradation of the other PKC isoforms, may be explained by the
      finding that this kinase isoform is predominantly associated with the cell
      membrane. The different cellular localizations, as well as the different
      susceptibilities to calpain digestion, further support the hypothesis that in MEL
      cells the various PKC isoforms play distinct biological functions that are
      critical for the maintenance of the undifferentiated state of the cell and for
      its commitment to terminal erythroid differentiation.

PMID- 7826343
TI  - Thyroid hormone treatment alters phospholipid composition and membrane fluidity
      of rat brain mitochondria.
AB  - We examined effects of graded doses of thyroid hormones 3,3', 5-tri-iodo-L
      thyronine (T3) and L-thyroxine (T4) on the lipid composition of rat brain
      mitochondria. Neither hormone significantly affected the mitochondrial
      cholesterol or total phospholipid content, but did increase
      phosphatidylethanolamine (PE) at the expense of phosphatidylserine (PS),
      phosphatidylinositol (PI) and phosphatidylcholine (PC). The phosphatidic acid
      (PA) content was also elevated, suggesting enhanced phospholipid turnover.
      Changes in sphingomyelin (SPM) and diphosphatidylglycerol (DPG) were minimal.
      Mitochondrial membrane fluidity also increased after thyroid-hormone treatment,
      and the increase was closely correlated with PC/PE and SPM/PE molar ratios.

PMID- 7826344
TI  - Regulation of the efflux of putrescine and cadaverine from rapidly growing
      cultured RAW 264 cells by extracellular putrescine.
AB  - Cultures of the macrophage-like RAW 264 cells were adapted to divide normally in
      a synthetic serum-supplemented culture medium lacking any polyamines and diamine
      oxidase activity. These rapidly dividing cells actively effluxed large amounts of
      putrescine and cadaverine, compared with the intracellular levels, into the
      culture medium. The efflux of putrescine was stimulated by the amino acid
      ornithine, whereas efflux of cadaverine was inhibited. Relatively low levels of
      spermidine and N1-acetyl-spermidine, compared with those of exported putrescine,
      were observed to accumulate in the culture medium. A careful analysis of the
      changes in the intracellular concentration of putrescine relative to the steady
      state net rate of putrescine export, as the doubling time of the cultures
      increased from 16 h to 22 h, indicated that an inverse relationship existed
      between these two parameters. As the intracellular putrescine concentrations
      increased, the net rate of putrescine export decreased markedly. Determination of
      the rate of putrescine uptake indicated that putrescine uptake also decreased
      significantly as the cultures neared confluency, and at no time during the growth
      of the culture did the rate of putrescine uptake approximate to the high rate of
      putrescine efflux. The decrease in the putrescine export rate seen as the cells
      grew toward confluency was determined to be primarily due to the inhibitory
      effect of the effluxed putrescine in the medium (Ki = 2 microM), and not to
      contact inhibition. The data suggested that the efflux of putrescine and
      cadaverine is not mediated to a significant degree by a process involving simple
      diffusion.

PMID- 7826345
TI  - Activation of precursors for matrix metalloproteinases 1 (interstitial
      collagenase) and 3 (stromelysin) by rat mast-cell proteinases I and II.
AB  - Histological studies have previously demonstrated an association between mast
      cell activation/degranulation and areas of connective-tissue lysis in vivo; in
      addition, mast-cell extracts have been shown to activate latent forms of
      collagenase and stromelysin. In the present study we have examined the potential
      roles of rat mast-cell proteinase (RMCP) I and RMCP II as activators of the
      precursors of matrix metalloproteinase (MMP)-1 (interstitial collagenase), MMP-2
      (gelatinase A) and MMP-3 (stromelysin 1). Both RMCPs I and II activated proMMP-3
      by converting the 57 kDa precursor into a 45 kDa polypeptide. The N-terminal
      amino acid of 45 kDa MMP-3 activated by RMCP II was identified as Phe83. By
      contrast, only RMCP II activated the 52 kDa proMMP-1 by converting it into a 41
      kDa protein and generating the new N-termini, namely Gln80 and Val82. The
      collagenolytic activity which resulted from this cleavage was only 35% of the
      full activity, but this could not be augmented by subsequent treatment with MMP
      3, the latter being a crucial enzyme for the generation of the fully active MMP-1
      with Phe81 at the N-terminus, in conjunction with other serine proteinases. Thus
      RMCP II activates proMMP-1 via a mechanism different from that reported for the
      stepwise processing by combinations of other trypsin-like enzymes and MMP-3.
      ProMMP-2 (pro-gelatinase A) was not activated by either RMCP I or RMCP II,
      despite processing to smaller products.

PMID- 7826346
TI  - Isolation and structural characterization of the Leishmania donovani
      kinetoplastid membrane protein-11, a major immunoreactive membrane glycoprotein.
AB  - A novel membrane molecule, previously observed to be co-isolated with
      lipophosphoglycan and called lipophosphoglycan-associated protein, has been
      detected in Leishmania donovani promastigotes and amastigotes. This kinetoplastid
      membrane protein (KMP-11) has been purified by preparative SDS/PAGE after organic
      solvent extraction of promastigote membranes. Isoelectric-focusing experiments
      indicated that this was an acidic protein with an isoelectric point of 4.8.
      Immunoblot analysis of subcellular fractions, together with 125I-labelling
      experiments, showed this molecule to be associated with the promastigote cell
      surface membrane. KMP-11 was expressed at a copy number similar to that of
      lipophosphoglycan (1 x 10(6)-2 x 10(6) molecules per cell), making this
      glycoprotein one of the major features on the parasite cell surface. The primary
      structure, less a blocked N-terminal region, was determined by automated Edman
      degradation of peptides derived from CNBr or enzymic fragmentation. Several post
      translational modifications were also found during these studies, including an O
      linked oligosaccharide and an NG-monomethylarginine functionality which was
      verified by m.s. Finally, a set of sequential synthetic peptides was made based
      on the established partial sequence allowing structural determination of two
      distinct antibody-binding sites for the monoclonal antibodies L98 and L157.

PMID- 7826347
TI  - Cloning and structure-function analysis of the Leishmania donovani kinetoplastid
      membrane protein-11.
AB  - This report describes the complete translated gene sequence, predicted secondary
      structure and lipid bilayer association of a novel kinetoplastid membrane protein
      (KMP-11) from Leishmania donovani promastigotes. KMP-11 was previously referred
      to as the lipophosphoglycan-associated protein (LPGAP). The isolation, species
      distribution and chemical characterization, including a partial protein sequence
      analysis and post-translational modifications, of this major membrane component
      have been described [Jardim, Funk, Caprioli and Olafson (1995) Biochem. J. 305,
      307-313]. C.d. measurements of KMP-11 indicated a very high helical content
      estimated to be approximately 86% in trifluoroethanol. This was in agreement with
      computer-based secondary-structure analyses which predicted KMP-11 to be almost
      exclusively alpha-helical, with the protein adopting a helix-loop-helix motif.
      Arrangement of the residues located in the putative helical regions on an
      Edmundson helical wheel showed that this molecule could have a strongly
      amphipathic conformation and provided an explanation for how such a highly
      charged protein might be inserted into the plasma membrane. Evidence in support
      of KMP-11 association with lipid bilayers was provided by showing that KMP-11
      could mediate carboxyfluorescein release from liposomes. These findings suggested
      that KMP-11 may function in part to increase bilayer pressure, stabilizing
      molecules such as lipophosphoglycan within the parasite pellicular membrane.

PMID- 7826348
TI  - Mechanism of stimulation of microsomal UDP-glucuronosyltransferase by UDP-N
      acetylglucosamine.
AB  - We propose the existence in rat liver endoplasmic reticulum (ER) of two
      asymmetric carrier systems. One system couples UDP-N-acetylglucosamine
      (UDPGlcNAc) transport to UDP-glucuronic acid (UDPGlcA) transport. When UDPGlcNAc
      was presented at the cytosolic side of the ER, it then acted as a weak inhibitor
      of UDPGlcA uptake. By contrast, UDPGlcNAc produced a forceful trans-stimulation
      of microsomal UDPGlcA uptake when it was present within the lumen of the ER.
      Likewise, cytosolic UDPGlcA strongly trans-stimulated efflux of intravesicular
      UDPGlcNAc, whereas cytosolic UDPGlcNAc was ineffective in trans-stimulating
      efflux of UDPGlcA. A second asymmetric carrier system couples UDPGlcNAc transport
      to UMP transport. Microsomal UDPGlcNAc influx was markedly stimulated by UMP
      present inside the microsomes. Such stimulation was only apparent when microsomes
      had been preincubated and thereby preloaded with UMP, indicating that UMP exerted
      its effect on UDPGlcNAc uptake by trans-stimulation from the lumenal side of the
      ER membrane. Contrariwise, extravesicular UMP only minimally trans-stimulated
      efflux of intramicrosomal UDPGlcNAc. It is widely accepted that UDPGlcNAc acts as
      a physiological activator of hepatic glucuronidation, but the mechanism of this
      effect has remained elusive. Based on our findings, we propose a model in which
      the interaction of two asymmetric transport pathways, i.e. UDPGlcA influx coupled
      to UDPGlcNAc efflux and UDPGlcNAc influx coupled to UMP efflux, combined with
      intravesicular metabolism of UDPGlcA, forms a mechanism that leads to stimulation
      of glucuronidation by UDPGlcNAc.

PMID- 7826349
TI  - In vivo activity of glutaminase in the brain of hyperammonaemic rats measured by
      15N nuclear magnetic resonance.
AB  - The in vivo activity of phosphate-activated glutaminase (PAG) was measured in the
      brain of hyperammonaemic rat by 15N n.m.r. Brain glutamine was 15N-enriched by
      intravenous infusion of 15NH4+ until the concentration of [5-15N]glutamine
      reached 6.1 mumol/g. Further glutamine synthesis was inhibited by intraperitoneal
      injection of methionine-DL-sulphoximine, an inhibitor of glutamine synthetase,
      and the infusate was changed to 14NH4+ during observation of decrease in brain [5
      15N]glutamine due to PAG and other glutamine utilization pathways. Progressive
      decrease in brain [5-15N]glutamine, PAG-catalysed production of 15NH4+ and its
      subsequent assimilation into glutamate by glutamate dehydrogenase were monitored
      in vivo by 15N n.m.r. Brain [5-15N]glutamine (15N enrichment of 0.35-0.50)
      decreased at a rate of 1.2 mumol/h per g of brain. The in vivo PAG activity,
      determined from the observed rate and the quantity of 15NH4+ produced and
      subsequently assimilated into glutamate and aspartate, was 0.9-1.3 mumol/h per g.
      This activity is less than 1.1% of the reported activity in vitro measured in rat
      brain homogenate at a 10 mM concentration of the activator Pi. Inhibition by
      ammonia (brain level 1.4 mumol/g) alone does not account for the observed low
      activity in vivo. The result strongly suggests that, in intact brain, PAG
      activity is maintained at a low level by a suboptimal in situ concentration of Pi
      and the strong inhibitory effect of glutamate. The observed PAG activity in vivo
      is lower than the reported in vivo activity of glutamate decarboxylase which
      converts glutamate into gamma-aminobutyrate (GABA). The result suggests that PAG
      catalysed hydrolysis of glutamine is not the sole provider of glutamate used for
      GABA synthesis.

PMID- 7826350
TI  - Multiple substitutions at position 104 of beta-lactamase TEM-1: assessing the
      role of this residue in substrate specificity.
AB  - Residue 104 is frequently mutated from a glutamic acid to a lysine in the
      extended-spectrum TEM beta-lactamases responsible for the resistance to third
      generation cephalosporins in clinical Gram negative strains. Among class A beta
      lactamases, it is the most variable residue within a highly conserved loop which
      delineates one side of the active site of the enzymes. To investigate the role of
      this residue in the extended-spectrum phenotype, it has been replaced by serine,
      threonine, lysine, arginine, tyrosine and proline. All these substitutions yield
      active enzymes, with no drastic changes in kinetic properties compared with the
      wild-type enzyme, except with cefaclor, but an overall improved affinity for
      second- and third-generation cephalosporins. Only mutant E104K exhibits a
      significant ability to hydrolyse cefotaxime. Molecular modelling shows that the
      substitutions have generally no impact on the conformation of the 101-111 loop as
      the side chains of residues at position 104 are all turned towards the solvent.
      Unexpectedly, the E104P mutant turns out to be the most efficient enzyme. All our
      results argue in favour of an indirect role for this residue 104 in the substrate
      specificity of the class A beta-lactamases. This residue contributes to the
      precise positioning of residues 130-132 which are involved in substrate binding
      and catalysis. Changing residue 104 could also modify slightly the local
      electrostatic potential in this part of the active site. The limited kinetic
      impact of the mutations at this position have to be analysed in the context of
      the microbiological problem of resistance to third-generation cephalosporins.
      Although mutation E104K improves the ability of the enzyme to hydrolyse these
      compounds, it is not sufficient to confer true resistance, and is always found in
      clinical isolates associated with at least one mutation at another part of the
      active site. It is the combined effect of the two mutations that synergistically
      enhances the hydrolytic capability of the enzyme towards third-generation
      cephalosporins.

PMID- 7826351
TI  - Non-detergent sulphobetaines: a new class of mild solubilization agents for
      protein purification.
AB  - The action of non-detergent sulphobetaines (NDSBs) as new mild agents for protein
      purification is described. The solubilization effects of non-detergent
      sulphobetaines are shown in different examples; all obtained under non-denaturing
      conditions: (1) microsomal proteins extraction; (2) recovery after dialysis of
      nuclear proteins; (3) reduction of precipitation in isoelectric focusing
      experiments under non-denaturing conditions; and (4) purification of a membrane
      bound serine protease from Plasmodium falciparum involved in erythrocyte invasion
      by malaria merozoites. The absence of a significant denaturation effect induced
      by NDSBs is demonstrated by tests on beta-galactosidase and alkaline phosphatase.
      A simple NDSB synthesis and some possible explanations of the action of NDSBs are
      also presented.

PMID- 7826352
TI  - Purification and characterization of two forms of beta-D-galactosidase from rat
      epididymal luminal fluid: evidence for their role in the modification of sperm
      plasma membrane glycoprotein(s).
AB  - Previous studies from this laboratory have identified rat epididymal luminal
      fluid acid beta-D-galactosidase activity which also optimally hydrolyses a
      glycoprotein substrate at neutral pH [Skudlarek, Tulsiani and Orgebin-Crist
      (1992) Biochem. J. 286, 907-914]. We have now separated the luminal fluid beta-D
      galactosidase into two molecular forms by ion-exchange chromatography on a column
      of DE-52. The separated enzyme activities were purified to an apparent
      homogeneity by molecular-sieve chromatography followed by affinity chromatography
      on a column of immobilized p-nitrophenyl beta-D-thiogalactopyranoside. The
      purified forms, when resolved by SDS/PAGE under reducing conditions, showed
      apparent molecular masses of 84 and 97 kDa. Kinetic studies, including a pH
      dependent substrate preference and pH-dependent association/dissociation,
      disclosed no differences between these two forms. The two forms had identical N
      terminal amino acid sequences. However, the 97 kDa form contained much more total
      carbohydrate and sialic acid than the 84 kDa form. The carbohydrate moieties in
      the two forms were assessed by comparing their size on SDS/PAGE before and after
      treatment with endo-enzymes. The removal of N-linked glycans by treatment with N
      glycanase or endoglycosidase F generated de-N-glycosylated polypeptides of an
      apparent molecular mass of 70 kDa, and indicated that the two forms contained
      varying amounts of asparagine (N)-linked high mannose/hybrid-type and biantennary
      complex-type oligosaccharides. This result and the fact that the two molecular
      forms had identical N-terminal amino acid sequences indicated that the two forms
      probably have identical or very similar polypeptides. The potential role of the
      enzyme in modification of sperm plasma membrane (PM) glycoproteins was examined
      by resolving caput sperm PM proteins (before and after treatment in vitro of the
      membranes with the purified beta-D-galactosidase) on SDS/PAGE, followed by
      staining with peanut agglutinin (PNA), a lectin which preferentially binds to Gal
      beta 1,3GalNAc-linkages found in O-linked glycoproteins. The evidence presented
      in this report has indicated that a PNA-positive glycoprotein of an apparent
      molecular mass of 135-150 kDa present on the caput (but not cauda) sperm PM is
      degalactosylated by the digestion in vitro of the membranes with purified luminal
      fluid beta-D-galactosidase. This result suggests a possible role for the
      epididymal luminal fluid beta-D-galactosidases.

PMID- 7826353
TI  - Autocrine regulation of milk secretion by a protein in milk.
AB  - Frequency or completeness of milk removal from the lactating mammary gland
      regulates the rate of milk secretion by a mechanism which is local, chemical and
      inhibitory in nature. Screening of goat's milk proteins in rabbit mammary explant
      cultures identified a single whey protein of M(r) 7600 able to inhibit synthesis
      of milk constituents. The active whey protein, which we term FIL (Feedback
      inhibitor of Lactation), also decreased milk secretion temporarily when
      introduced into a mammary gland of lactating goats. FIL was synthesized by
      primary cultures of goat mammary epithelial cells, and was secreted vectorially
      together with other milk proteins. N-terminal amino acid sequencing indicated
      that it is a hitherto unknown protein. The evidence indicates that local
      regulation of milk secretion by milk removal is through autocrine feedback
      inhibition by this milk protein.

PMID- 7826354
TI  - Thiocyanate, a plausible physiological electron donor of gastric peroxidase.
AB  - Gastric peroxidase (GPO) was purified to apparent homogeneity to characterize its
      major physiological electron donor. The enzyme (RZ = 0.7), with a subunit
      molecular mass of 50 kDa, is a glycoprotein, with a relative abundance of
      aspartic and glutamic acid over arginine and lysine. It has a Soret maximum at
      412 nm, which is shifted to 426 nm by H2O2 due to formation of compound II.
      Although the physiological electron donors I-, Br- and SCN-, but not Cl-, are
      oxidized by GPO optimally at acid pH, only I- and SCN- are oxidized appreciably
      at physiological pH. Considering that the I- concentration in stomach is less
      than 1 microM, whereas the SCN- concentration is about 250 microM, SCN- may act
      as a major electron donor for GPO. Moreover, SCN- oxidation remains unaltered in
      the presence of physiological concentrations of other halides. The second-order
      rate constant for the reaction of GPO with H2O2 (k1) and compound I with SCN-
      (k2) at pH 7 was found to be 8 x 10(7) M-1.s-1 and 2 x 10(5) M-1.s-1
      respectively. GPO has significant pseudocatalase activity also in the presence of
      I- or Br-, but it is blocked by SCN-. The SCN- oxidation product OSCN- may be
      reduced back to SCN- by cellular GSH, and GSSG may be reduced back to GSH by
      glutathione reductase and NADPH. In a system reconstituted with pure glutathione
      reductase, NADPH, GSH, SCN- and H2O2. GPO-catalysed SCN- oxidation could be
      coupled to NADPH oxidation. This system where GPO utilizes SCN- as the major
      physiological electron donor may operate efficiently to scavenge intracellular
      H2O2.

PMID- 7826355
TI  - Expression of the phosphoenolpyruvate carboxykinase gene in 3T3-F442A adipose
      cells: opposite effects of dexamethasone and isoprenaline on transcription.
AB  - The enzyme phosphoenolpyruvate carboxykinase (PEPCK) plays a key role in
      gluconeogenesis in liver and in glyceroneogenesis in adipose tissue. These
      processes, and PEPCK, are regulated by a number of hormones, some of which have
      different effects on the enzyme in liver and adipose tissue. To explore this
      phenomenon, PEPCK gene expression was studied in 3T3-F442A adipocytes maintained
      in a serum-free medium. The beta-adrenergic agonist isoprenaline (isoproterenol)
      and a cyclic AMP analogue (8-CPT-cAMP) increased PEPCK mRNA. A maximal 3-fold
      induction occurred in 2 h. Dexamethasone decreased PEPCK mRNA by 80% in 4 h.
      Dexamethasone also counteracted the inductive effects of isoprenaline and 8-CPT
      cAMP. Run-on transcription experiments showed that the isoprenaline and
      dexamethasone actions were, at least in part, exerted at the level of PEPCK gene
      transcription. These effects were further analysed by using transient and stable
      transfection of adipocytes with a plasmid containing bp -2100 to 69 of the PEPCK
      gene promoter fused to the chloramphenicol acetyltransferase (CAT) gene. In such
      cells isoprenaline stimulated CAT expression, an effect that was prevented if the
      cells were also exposed to dexamethasone.

PMID- 7826356
TI  - Regulation of hepatocyte plasma membrane alpha 1-adrenergic receptors by 4 beta
      phorbol 12-myristate 13-acetate.
AB  - The effect of phorbol 12-myristate 13-acetate (PMA) on hepatocyte alpha 1
      adrenergic receptors was determined by [3H]prazosin binding to plasma membranes
      from control and PMA-treated hepatocytes. Membranes from hepatocytes incubated
      with PMA (1 microgram/ml) for 1 h exhibited a 40% decrease in alpha 1-adrenergic
      receptors (481 +/- 10 fmol/mg of protein; mean +/- S.E.M. for three separate
      experiments) relative to vehicle-treated (dimethylformamide) hepatocytes (802 +/-
      91 fmol/mg of protein; n = 3), with no significant effect on the KD. The PMA
      induced decrease in alpha 1-adrenergic receptors was maximal by 30 min and half
      maximal inhibition of [3H]prazosin binding occurred with a PMA concentration of
      approx. 15 ng/ml. Pretreatment of hepatocytes with staurosporine (5 microM)
      blocked the effect of PMA, and 4 beta-phorbol 13-monoacetate was ineffective,
      suggesting the involvement of protein kinase C (PKC). Treatment of hepatocytes
      with primaquine (300 microM) for 15 min decreased hepatocyte plasma membrane
      alpha 1-adrenergic receptors by 34.0 +/- 2.4% (mean +/- S.E.M. of three
      experiments). Removal of primaquine allowed essentially complete recovery (98 +/-
      4%; mean +/- S.E.M. for five separate experiments) of plasma membrane
      [3H]prazosin binding within 20 min, suggesting that the alpha 1-adrenergic
      receptor undergoes endocytotic recycling. Addition of PMA (1 microgram/ml) to
      hepatocytes immediately after removal of primaquine, completely inhibited the
      increase in plasma membrane alpha 1-adrenergic receptors relative to control
      cells, but had no effect on hepatocytes whose cell surface alpha 1-receptors
      remaining after primaquine treatment had been inactivated by alkylation. These
      observations suggested that activation of PKC may facilitate the internalization
      of the alpha 1-adrenergic receptor in hepatocytes.

PMID- 7826357
TI  - Cloning and functional expression of a Na(+)-dependent phosphate co-transporter
      from human kidney: cDNA cloning and functional expression.
AB  - A cDNA clone encoding a protein 69% identical in amino acid sequence with that of
      the Na/P(i) co-transporter NaP(i)-1 was isolated from a human kidney cDNA
      library. The DNA sequence was identical with that of NPT-1 cDNA published by
      Chong, Kristjansson, Zoghbi and Hughe (1993) (Genomics, 18, 355-359). In the
      present study, we have characterized the function of the encoded protein and the
      tissue distribution of its mRNA. Injection of RNA transcribed from NPT-1 into
      Xenopus oocytes resulted in expression of Na/P(i) co-transport activity showing a
      high affinity for P(i) transport (Km 0.29 mM). Kinetic characterization ([P(i)],
      [Na+]) demonstrated that the expressed transport activity has properties similar
      to those displayed by oocytes injected with human kidney poly(A)+ RNA. Northern
      blotting demonstrated that NPT-1 mRNA is expressed in renal cortex, liver and
      brain but not in other tissues. Hybrid depletion with antisense oligonucleotides
      to NaP(i)-3 and NPT-1 completely inhibited poly(A)+ RNA-induced Na(+)-dependent
      P(i) uptake in oocytes. These findings indicate that two high-affinity Na/P(i)
      cotransporters (NaP(i)-3 and NPT-1) are present in human kidney cortex.

PMID- 7826358
TI  - Physical and biological characterization of a growth-inhibitory activity purified
      from the neuroepithelioma cell line A673.
AB  - Epithelial- and haematopoietic-cell growth-inhibitory activities have been
      identified in the conditioned medium of the human peripheral neuroepithelioma
      cell line A673. An A673-cell-derived growth-inhibitory activity was previously
      fractionated into two distinct components which inhibited the proliferation of
      human carcinoma and leukaemia cells in culture. One inhibitory activity was shown
      to comprise interleukin-1 alpha (IL-1 alpha). Here, we have purified to
      homogeneity a distinct activity which inhibited the growth of the epithelial
      cells in vitro. Using a combination of protein-sequence analysis and mass
      spectrometry, we demonstrated that biological activity can be assigned to a
      dimeric protein with a molecular mass of 25,576 (+/- 4) Da and an N-terminal
      sequence identical with that of transforming growth factor-beta 1 (TGF-beta 1).
      Further characterization of the growth inhibitor with TGF-beta-isoform-specific
      antibodies showed that > 90% of the bioactivity consists of TGF-beta 1 and not
      TGF-beta 2 or TGF-beta 3. Although A673 cells were growth-inhibited by exogenous
      TGF-beta 1, we showed that TGF-beta 1 in A673-cell-conditioned media was present
      in the latent, biologically inactive, form which did not act as an autocrine
      growth modulator of A673 cells in vitro.

PMID- 7826359
TI  - Interaction of cholesterol-crystallization-promoting proteins with vesicles.
AB  - In this study, the interaction of mucin and concanavalin A-binding proteins
      isolated from human bile with cholesterol/phospholipid vesicles was investigated.
      Using resonance energy transfer assays originally developed by Struck, Hoekstra
      and Pagano [(1981) Biochemistry 20, 4093-4099], no significant protein-induced
      fusion or aggregation of vesicles was demonstrated. Instead of fusion, these
      proteins induced destabilization of cholesterol/phospholipid vesicles, as
      monitored by release of entrapped carboxyfluorescein. A good correlation (rho =
      0.81) was obtained between the extent of leakage and the nucleation-promoting
      activity of the concanavalin A-binding proteins. We conclude that aggregation or
      fusion of cholesterol/phospholipid vesicles is not an obligatory step in
      cholesterol crystallization. Biliary protein-induced crystallization seems to be
      preceded by vesicle disruption.

PMID- 7826361
TI  - Tyr13 is essential for the activity of omega-conotoxin MVIIA and GVIA, specific N
      type calcium channel blockers.
AB  - Two analogs of omega-conotoxin MVIIA, a 25mer peptide neurotoxin, were
      synthesized by replacing Lys2 or Tyr13 with Ala. The activities of synthetic
      analogs were estimated from the inhibitory action on 125I-omega-conotoxin GVIA
      binding to chick brain synaptic plasma membranes. As in the case of omega
      conotoxin GVIA, replacement of Tyr13 resulted in an enormous reduction in
      activity. In contrast, substitution of Ala for Lys2 gave only a small effect.
      These results indicate that Tyr13 is a critical amino acid of omega-conotoxin
      MVIIA and GVIA for blocking N-type calcium channel function.

PMID- 7826360
TI  - Doc2: a novel brain protein having two repeated C2-like domains.
AB  - Two repeated C2-like domains interacting with Ca2+ and phospholipid are found in
      synaptotagmin and Rabphilin-3A which are implicated in neurotransmitter release.
      Here we have isolated a cDNA encoding a novel protein having two repeated C2-like
      domains from a human brain cDNA library. The isolated cDNA encodes a protein with
      400 amino acids and a M(r) of 44,071. The purified recombinant protein indeed
      interacts with Ca2+ and phospholipid. We have named this protein Doc2 (Double
      C2). Doc2 is exclusively expressed in brain and is highly concentrated in the
      synaptic vesicle fraction. These results suggest that Doc2 is a novel brain
      protein and serves as a Ca2+ sensor in neurotransmitter release.

PMID- 7826362
TI  - PGF2-isoprostanes formed during copper-induced oxidation of low-density
      lipoproteins are the prostaglandins that cross-react with PGE2 antibodies.
AB  - It has been previously shown that LDL oxidation can produce a prostaglandin
      artifact(s) which cross-reacts with PGE2 antibodies. The nature of this cross
      reacting material had not been identified. In this study we have examined the
      products of LDL oxidation and found substances cross-reacting with both PGE2 and
      LTB4 antibodies. Lipid extracts of copper oxidised LDL were separated by reverse
      phase HPLC and fractions cross-reacting with PGE2 antibody identified. Fractions
      were collected and examined by GC-MS as methyl ester TMS ether derivatives. 8-epi
      PGF2 alpha (8-isoprostane) was identified as one of the major metabolites eluting
      in fractions cross-reacting with PGE2. 8-epi-PGF2 alpha showed 4% cross
      reactivity with a PGE2 antibody but very little with LTB4 or thromboxane B2
      antibodies. Treatment of oxidised LDL with a specific 8-isoprostane antibody
      removed any detectable PGE2 levels in subsequent PGE2 RIA. The generation of
      cross-reacting material during LDL oxidation was not influenced by indomethacin.
      The generation of 8-isoprostanes by free radical oxidation of arachidonic acid in
      LDL may explain much of the cross-reactivity seen with PGE2 antibodies. The
      identity of substances cross-reacting with LTB4 have yet to be identified.

PMID- 7826363
TI  - Synthetic peptides derived from midkine enhance plasminogen activator activity in
      bovine aortic endothelial cells.
AB  - Chemically synthesized human midkine enhanced plasminogen activator activity and
      decreased its inhibitor levels in bovine aortric endothelial cells. These
      activities were preserved in the C-terminal half, but not in the N-terminal half
      of the midkine molecule. Furthermore, a synthetic peptide of 43 amino acids
      designated as "C-domain", which formed the compact structure held by two
      disulfide bonds in the C-terminal half, mimicked intact midkine. Chemically
      synthesized C-domain of pleiotrophin (43 amino acids), which was 53% identical to
      midkine C-domain in amino acid sequence, expressed the similar activities. These
      43 amino acid peptides are, so far, the shortest peptide able to enhance the
      fibrinolytic activities of the endothelial cells.

PMID- 7826364
TI  - Detection of hydrogen peroxide and hydroxyl radicals in murine skin fibroblasts
      under UVB irradiation.
AB  - The purpose of this study was to identify the active oxygen species generated in
      murine skin fibroblasts under UVB irradiation. When fibroblasts were exposed to
      UV light (UVA + UVB), hydroxyl radicals were detectable by ESR-spin trapping
      using DMPO as a spin trapping agent. Cell damage induced by UVB irradiation was
      prevented by addition of DMSO, a typical hydroxyl radical scavenger. Fibroblasts
      treated with a catalase inhibitor 3-amino-1H-1,2,4-triazole were more sensitive
      to UVB irradiation than untreated-cells, but the sensitivity was improved by
      addition of DMSO. To find the origin of the hydroxyl radicals in fibroblasts
      during UVB irradiation, H2O2 was determined by dihydrorhodamine 123 and it was
      found that the formation of H2O2 increased under UVB irradiation. These results
      suggest that UVB-irradiated skin fibroblasts produce H2O2 and were followed by
      the formation of hydroxyl radicals, probably derived from the Fenton-like
      reaction (H2O2 + Fe2+ --> .OH + OH- + Fe3+), which in turn damages the cells.

PMID- 7826365
TI  - A specific tetrahydrobiopterin binding domain on tyrosinase controls
      melanogenesis.
AB  - (6R)5,6,7,8-tetrahydrobiopterin (6-BH4) directly regulates tyrosinase activity by
      specifically binding to a putative 13 amino acid domain. This domain has sequence
      homology to 6-BH4 binding sites already identified on phenylalanine hydroxylase
      and 4a-carbinolamine dehydratase. Furthermore, this binding sequence appears to
      have been conserved during the evolution of tyrosinase as it has also been
      identified in the frog, mouse and human enzymes. 6-BH4 controls tyrosinase
      activity by an uncompetitive mechanism requiring the presence of L-tyrosine for
      effective down-regulation. When L-dopa is substrate, 6-BH4 does not inhibit the
      enzyme implicating separate binding sites for L-dopa and L-tyrosine on
      tyrosinase. Dihydropterin and 6-biopterin, the oxidation products of 6-BH4, do
      not inhibit tyrosinase significantly, indicating that melanin biosynthesis is
      controlled by a 6-BH4/6-biopterin redox-switch mechanism which can be initiated
      by photo-oxidation of 6-BH4.

PMID- 7826366
TI  - Induction of resistance to 1-beta-D-arabinofuranosylcytosine in human H9 cell
      line by simian immunodeficiency virus.
AB  - We examined drug sensitivity of human T cell acute lymphoblastic leukemia H9
      cells chronically infected with simian immunodeficiency virus (SIVmac) and found
      that the retrovirus-infected H9 cells showed 8.2-fold resistance to 1-beta-D
      arabinofuranosylcytosine (Ara-C). In the infected cells, Ara-CTP levels decreased
      to 20% of that found in uninfected H9 cells after 3 h incubation at Ara-C
      concentration of 1 microM, and 8.1-fold increase of cytidine deaminase activity
      was observed in the infected H9 cells. A competitive inhibitor of cytidine
      deaminase, 3, 4, 5, 6-tetrahydrouridine (THU), at 100 microM reversed Ara-C
      resistance in the infected cells. These results indicate that inducing increased
      cytidine deaminase activity by SIVmac infection conferred Ara-C resistance to H9
      cells. An understanding of these cellular differences in drug sensitivity may aid
      in the development of therapeutic strategies against retrovirus-infected cells.

PMID- 7826367
TI  - Hydrophobic accessible surface areas are proportional to binding energies of
      serine protease-protein inhibitor complexes.
AB  - For analysis of enzyme-protein inhibitor interactions, we calculated the buried
      hydrophobic and hydrophilic accessible surface areas (ASAs) of enzymes and
      primary contact regions. In the five enzyme-protein inhibitor complexes so far
      analyzed, we found that the hydrophobic ASAs buried between the enzyme and the
      primary contact region are proportional to their experimental binding energies.
      This finding indicates that the hydrophobic interaction drives the binding of
      enzymes with protein inhibitors.

PMID- 7826368
TI  - Enhanced E-cadherin expression in epidermal growth factor receptor expressing
      cells.
AB  - Expression of the epidermal growth factor receptor (EGFr) and the cell-cell
      adhesion molecule E-cadherin have individually been implicated in the biological
      activity of the most common human malignancies. There is also evidence for
      colocalization and for a correlation in the expression of these two proteins in
      human cells. To better define the relationship between these two gene products,
      we used immunohistochemistry and Western blot analysis to compare E-cadherin
      expression in various well characterized cell lines lacking expression of EGFr or
      expressing wild type, functional mutant or non functioning mutant EGFr. Parental
      NR6 cells, which lack endogenous EGFr, and a derivitive cell line NR6M721, which
      expresses EGFr lacking tyrosine kinase activity, showed low levels of E-cadherin
      expression with or without stimulation with EGF. In contrast, the derivative
      NR6c'973 cell line, which expresses an active EGFr defective in EGF induced
      internalization and down-regulation and NR6 cells expressing wild type EGFr
      showed strong E-cadherin expression. These results suggest that EGFr activation
      may regulate or enhance E-cadherin expression.

PMID- 7826369
TI  - In vivo transfection of genes for renin and angiotensinogen into the glomerular
      cells induced phenotypic change of the mesangial cells and glomerular sclerosis.
AB  - Locally activated renin angiotensin system plays an important role in the
      progression of the glomerular diseases. In order to understand the local effect
      of overexpressed angiotensin II in the glomerulus in situ, we introduced human
      genes for renin and angiotensinogen into the rat kidney by hemagglutinating virus
      of Japan-liposome procedure. Three days after transfection human renin was
      detected in the glomeruli by immunohistochemistry. Seven days after transfection,
      extracellular matrix was expanded in the glomeruli and alpha-smooth muscle actin
      was expressed in the mesangial cells. These results suggest that locally
      activated renin angiotensin system induces glomerular sclerosis and a phenotypic
      change in mesangial cells.

PMID- 7826370
TI  - Proteolytic release of human angiotensin-converting enzyme expressed in Chinese
      hamster ovary cells is enhanced by phorbol ester.
AB  - Membrane-bound angiotensin-converting enzyme (ACE) expressed in Chinese hamster
      ovary (CHO) cells is proteolytically released in soluble form into the medium. We
      find that this release is stimulated up to 50-fold by phorbol-12,13-dibutyrate
      and also by the addition of fresh, serum-containing media. Concomitant with the
      enhanced release is a marked decrease in levels of membrane-bound ACE, down to 7%
      of resting levels in the case of phorbol ester stimulation. Staurosporine, a
      protein kinase C (PKC) inhibitor, abolishes the phorbol ester effect. Kinetic
      analysis of the stimulated release rate indicates that it is first order, likely
      due to substrate depletion; calculated half times, t1/2, are 174 +/- 12 min and
      40 +/- 6 min for the media-change and phorbol ester stimulated rates,
      respectively. Thus, release of membrane-bound ACE in CHO cells is regulated, in
      part, by a PKC-dependent mechanism.

PMID- 7826371
TI  - Possible correlation between DNA damage induced by hydrogen peroxide and
      translocation of heat shock 70 protein into the nucleus.
AB  - Oxygen radicals have been implicated as the causative agent in deleterious
      processes such as gene mutation, cellular transformation and cell death. Cellular
      response to DNA damage induced by hydrogen peroxide was examined in human
      amniotic cultured cells (WISH). The content of 8-hydroxydeoxyguanosine in nuclear
      DNA increased during the early period of exposure to hydrogen peroxide, that is,
      it peaked at 1 h in the cells treated with 1 mM hydrogen peroxide and then
      declined, but not to the control levels within 4 h. Interestingly,
      immunofluorescence staining of treated cells revealed that cytoplasmic hsp70
      protein translocated transiently into the nucleus, which was most remarkable
      around 30 min after the addition of 1 mM hydrogen peroxide into the culture
      medium. On the other hand, the induction of hsp70 gene mRNA was not significant
      during the early period of treatment by 0.5 mM hydrogen peroxide and was occurred
      after 5 h. DNA damage induced by Adriamycin further supported the possible
      correlation between hydroxyl radical-mediated cleavage of DNA and nuclear
      translocation of hsp70 protein. These results suggest that preexisting hsp70
      protein translocated into the nucleus to either protect chromatin DNA from
      further damage or to facilitate the repair of DNA damage in some unknown ways.

PMID- 7826372
TI  - Dramatic species differences in the susceptibility of monoamine oxidase B to a
      group of powerful inhibitors.
AB  - Oxadiazolones and oxadiazolethiones are potent, reversible competitive inhibitors
      of MAO B in rat brain mitochondria. We have compared the Ki values of six of
      these inhibitors towards MAO B from rat, human and beef liver mitochondria, using
      benzylamine as substrate. Unexpectedly, their inhibitory potency varies by 3 to 4
      orders of magnitude between rat and beef liver MAO B, whereas the inhibition of
      the rat and human liver enzymes is quite similar. Examples are 5-(4-benzyl
      oxyphenyl)-3-(2-cyano-ethyl)-1,3,4-oxadiazole-2(3H)-th ione, with Ki at 30
      degrees of 0.5 nM for rat, 0.8 nM for human, and 1,830 nM for beef liver
      mitochondria and 5-(4-benzyloxyphenyl)-3-(2-hydroxyethyl)-1,3,4-oxadiazol-2(3 H)
      one with Ki values of 1.2, 1.1 and 1,320 nM for MAO B from these three sources.
      Since solubilized and membrane-bound enzymes had similar sensitivities to the
      inhibitors, the differences seen must arise from differences in the amino acid
      sequences of the three enzymes.

PMID- 7826373
TI  - Alternative form of the dicluster ferredoxin from the thermoacidophilic archaeon,
      Sulfolobus sp. strain 7.
AB  - An alternative form of a 7Fe dicluster-type ferredoxin (Fd-B) with a different
      charge density was purified as a minor component from the aerobic and
      thermoacidophilic archaeon, Sulfolobus sp. strain 7. Comparison of its properties
      with those of native 7Fe ferredoxin (Fd-A), a major ferredoxin, was made in terms
      of the molecular properties, the absorption, circular dichroism and electron
      paramagnetic resonance spectral properties, and the reactivity coupled with the
      cognate 2-oxoacid:ferredoxin oxidoreductase at 50 degrees C. Our results suggest
      that the Sulfolobus 7Fe ferredoxin has two spectroscopically distinct forms with
      slightly different conformations.

PMID- 7826374
TI  - A bifunctional monocyclic beta-lactam cross-links across the active site of beta
      lactamase.
AB  - A 4-alkoxy-2-azetidinone behaves as a bifunctional active site-directed inhibitor
      of the class A beta-lactamase from Bacillus cereus 569/H. It cross-links SER 70
      and LYS 234 as it binds in a approximately 1:1 ratio. The cross-linked enzyme is
      irreversibly inhibited while the secondary structure is partially stabilized
      under conditions when the native enzyme is otherwise converted to a form with no
      detectable secondary structure by circular dichroism.

PMID- 7826375
TI  - Cloning and sequencing of the cDNA for the light subunit of human liver gamma
      glutamylcysteine synthetase and relative mRNA levels for heavy and light subunits
      in human normal tissues.
AB  - We have cloned and sequenced a full length cDNA for the light subunit of human
      liver gamma-glutamylcysteine synthetase (GCS1). The GCS1 cDNA consists of 1628
      bp, containing an open reading frame of 822 bp which encodes a protein of 274
      amino acids having a calculated M(r) of 30,729 Daltons. Human liver GCS1 shares
      91% and 96% sequence homology at the nucleotide and amino acid levels,
      respectively, with its rat counterpart (Huang, Anderson and Meister, J. Biol.
      Chem. 268:20578-20583, 1993). Transcripts of 1.4 and 4.1 kb in length were
      detected by Northern blot analysis of mRNA isolated from each of sixteen
      different human tissues. Relative expression of the two GCS1 RNA transcripts was
      highly tissue-dependent. High steady-state levels of the smaller transcript were
      detected in colon, while very high levels of both transcripts were found in
      skeletal muscle. Expression of mRNA transcripts for the GCS heavy subunit were
      likewise tissue-dependent, and did not necessarily correlate with the level of
      GCS1 transcripts in any tissue.

PMID- 7826376
TI  - A fibroblast elongation factor purified from colon carcinoma cells shares
      sequence identity with TIMP-1.
AB  - We have previously reported that human colon cancer cells secrete a factor(s)
      which induces elongation of colon fibroblasts in vitro. Isolation of this factor
      led to the identification of a 55kD protein with fibroblast stretching activity.
      Two internal amino acid sequences identified in this protein (YEI; GFQALGDAADI)
      share complete homology with tissue inhibitor of metalloproteinase (TIMP-1).

PMID- 7826378
TI  - Cloning of a new member of the TGF-beta family: a putative new activin beta C
      chain.
AB  - The complete amino acid sequence of a new member of the TGF-beta superfamily has
      been determined through initial degenerate PCR, subsequent cloning and nucleotide
      sequencing of the human cDNA. Amino acid homology comparison among members of
      this superfamily suggests it to be a new member of the activin/inhibin subgroup.
      The proposed mature part of the precursor shows 53% amino acid identity to the
      activin beta B and 51% identity to the activin beta A chain whereas beta A and
      beta B show an identity of 64% to each other.

PMID- 7826377
TI  - Rabbit P450 2E1 expressed in CHO-K1 cells has a short half-life.
AB  - Rabbit P450 2E1 was stably expressed in Chinese hamster ovary cells after
      cotransfection with pRC/CMV-2E1 and pFR400 which expresses murine dihydrofolate
      reductase with a single arginine to leucine substitution at position 22. This
      mutation permits amplification of expression with increasing methotrexate
      concentrations in CHO-K1 cells that are not dihydrofolate reductase deficient.
      After amplification with 1 microM methotrexate, a representative clone expressed
      about 15 pmol of P450 2E1/mg microsomal protein. Cells from a single 35-mm plate
      catalyzed the formation of 1.02 nmol 6-hydroxychlorzoxazone/10(6) cells/h or
      about 127 pmol/mg total cell protein/min. The enzyme was rapidly labeled when
      pulsed with [35S]-methionine. Initial pulse-chase experiments indicate that the
      expressed protein has a half-life of 4.8 h.

PMID- 7826379
TI  - Protein kinase C delta accepts GTP for autophosphorylation.
AB  - Protein kinase C delta (PKC delta) from porcine spleen exhibits a marked capacity
      for autophosphorylation. Autophosphorylation is much more efficient in the
      presence of GTP than of ATP (6-fold). 15 mol phosphate/mol enzyme is incorporated
      with GTP as phosphate donor. The activity of PKC delta for autophosphorylation
      with ATP is around 4 times that of the isoenzymes alpha, beta, gamma (cPKC), and
      with GTP it is around 24 times that of cPKC. The catalytic subunit of protein
      kinase A and the tyrosine kinase src are not or only slightly autophosphorylated
      in the presence of GTP. The autophosphorylation of PKC delta with GTP does not
      differ from that with ATP regarding its activation by TPA or bryostatin, its
      inhibition by staurosporine, the type of phosphorylated amino acids (serine and
      threonine) and the mode of reaction (intrapeptide reaction). However, different
      sites are phosphorylated with GTP and ATP, as indicated by the amount of
      phosphate incorporated and by phosphopeptide mapping.

PMID- 7826380
TI  - Enhancement of monocyte adhesion to endothelial cells by oxidatively modified low
      density lipoprotein is mediated by activation of CD11b.
AB  - Treatment of human peripheral blood monocytes with oxidized (oxLDL), minimally
      modified low-density lipoprotein (mmLDL) or lysophosphatidylcholine (LPC) for 24h
      was associated with macrophage-like differentiation, as assessed by
      morphology/CD14 expression. Suppression of these effects by staurosporin (STS)
      indicated the dependence on protein kinase C (PKC) activation. OxLDL and mmLDL
      increased monocyte adhesion to human umbilical vein endothelial cells 2-fold.
      Enhancement of adhesion was prevented by an anti-CD11b mAb, demonstrating the
      involvement of CD11b. While LPC increased monocyte adhesion, inhibition of PKC by
      STS reversed enhancement of adhesion by oxLDL, showing mediation by LPC-induced
      PKC activation. OxLDL, mmLDL or LPC increased CD11b expression and stimulated a
      distinct peak in fluorescence intensity, suggesting that CD11b activation was
      crucial for enhanced monocyte adhesion.

PMID- 7826381
TI  - New insights on the specificity of penicillin acylase.
AB  - In contrast with the general thought that penicillin G acylases (PGAs) were only
      able to hydrolyse amides or esters of higly hydrophobic acids, we have
      demonstrated that the PGA from Kluyvera citrophila catalysed the hydrolysis of 4
      nitrophenyl esters of acetic, propionic, butyric and valeric acids. Values of
      kcat. and kcat./Km were greatest for the first compound and less than values for
      benzylpenicillin by factors of 30 and 7, respectively. 4-Nitrophenyl acetate was
      hydrolysed faster than 2-nitrophenyl acetate but slower than phenyl acetate. The
      pH dependence of the reaction was similar to that of benzylpenicillin. Several
      experiments showed that hydrolysis of 4-nitrophenyl acetate was not catalysed by
      contaminating esterase activity. The implications for the structural basis of
      substrate binding are discussed. These substrates open, for the first time, a way
      to investigate the kinetic parameters of PGA at the presteady-state and provides
      a new perspective about the role of PGA in nature.

PMID- 7826382
TI  - Specific labeling of isoprenylated proteins: application to study inhibitors of
      the post-translational farnesylation and geranylgeranylation.
AB  - Specific labeling of either farnesylated or geranylgeranylated proteins in human
      PC-3 prostate cancer cell line was obtained by suppression of mevalonic acid
      biosynthesis with lovastatin, 50 microM, followed by supplementation of cell
      culture medium with either [3H]farnesyl- or [3H]geranylgeranyl-pyrophosphate. The
      immunoprecipitation of either a farnesylated (p21 ras) or geranylgeranylated (p21
      rap 1) protein demonstrated that labeling was specific since proteins were
      detected only if the appropriate isoprenoid was added to the culture medium. TLC
      analysis indicated that no conversion of one isoprenoid to the other occurred in
      these conditions. The selective labeling of either farnesylated or
      geranylgeranylated proteins may be a valuable tool for the development of
      inhibitors of isoprenoid transferases as a potential new class of antitumor
      agents.

PMID- 7826383
TI  - Isolation of chicken hsp90 beta gene promoter.
AB  - In order to define the mechanisms responsible for the differential expression of
      chicken hsp90 alpha and beta genes, a portion of the chicken hsp90 beta genomic
      sequence, including 3081 bp upstream from the transcription initiation site and
      2718 bp of structural gene sequence which covers 7 exons and 6 introns was
      investigated. The transcriptional initiation site was determined by primer
      extension, RNAase and S1 nuclease mapping, Northern blot and cloning of 5' end of
      cDNA. The first intron, as in other hsp90 genes, is located just before the ATG
      initiation codon. Three Sp1 sites are located near the TATA box. The apparent
      major divergence with the hsp90 alpha promoter is that, in the hsp90 beta
      promoter, the only CAAT box and HSE element are located at about 3 and 2 kb
      upstream the TATA box, respectively. These features may explain why chicken hsp90
      beta mRNA is generally less abundant than alpha and is not inducible by heat
      shock or serum/growth factor stimulation.

PMID- 7826384
TI  - Mechanism of inhibition of protein phosphatase 1 by DARPP-32: studies with
      recombinant DARPP-32 and synthetic peptides.
AB  - The mechanism of inhibition of protein phosphatase-1 catalytic subunit (PP-1c) by
      recombinant DARPP-32 and synthetic peptides was studied. DARPP-32 was expressed
      in Escherichia coli as a non-fusion protein using a pEt-3a plasmid, purified to
      homogeneity and shown to have physicochemical properties similar to those of the
      protein purified from bovine brain. Recombinant DARPP-32 phosphorylated on
      threonine-34 by cAMP-dependent protein kinase inhibited PP-1c with an IC50
      approximately 0.5 nM, comparable to that obtained with bovine DARPP-32. Non
      phosphorylated DARPP-32, and mutated forms in which threonine-34 was replaced by
      an alanine or a glutamic acid, inhibited PP-1c with an IC50 approximately 1
      microM. Surface plasmon resonance analysis showed binding of PP-1c to nonphospho-
      and phospho-DARPP-32-(8-38) synthetic peptides with apparent Kd values of 1.2 and
      0.3 microM, respectively, supporting the existence of an interaction between non
      phosphorylated DARPP-32 and PP-1c that is increased by phosphorylation of DARPP
      32 at threonine-34. These results suggest a model in which DARPP-32 interacts
      with PP-1c by at least two low affinity sites, the combination of which is
      responsible for the high affinity (nM) inhibition.

PMID- 7826385
TI  - Cytosolic calcium is essential in the basal expression of tyrosine hydroxylase
      gene.
AB  - To test the role of cytosolic calcium in the basal expression of a neuronal gene,
      promoter activity of the rat tyrosine hydroxylase (TH) gene was monitored upon
      reduced resting level of intracellular calcium. TH promoter activity was
      decreased by cell-permeable calcium chelator, BAPTA/AM, in SK-N-BE(2)C human
      neuroblastoma cells. The cAMP response element (CRE) was mapped to the calcium
      responsible element by mutational and deletional analysis of the 5' upstream
      promoter region. Gel shift assay showed 2 CRE-specific DNA-protein complexes. The
      quantities of specific complexes were markedly decreased in BAPTA/AM-treated
      cells. These data suggest that resting level of intracellular calcium has a
      critical role in the basal expression of TH gene through the regulation of the
      binding of nuclear proteins to the CRE motif in the promoter.

PMID- 7826386
TI  - Inhibition of cardiac sarcolemmal sodium-calcium exchanger by
      glycerophosphoinositol 4-phosphate and glycerophosphoinositol 4-5-bisphosphate.
AB  - The enrichment in phosphatidylinositol 4-phosphate and phosphatidylinositol 4-5
      bisphosphate of cardiac sarcolemmal vesicles stimulate Na+/Ca2+ exchange
      activity. On the contrary the deacylation products of polyphosphoinositides are
      powerful inhibitors of Na+/Ca2+ exchange: half maximal inhibition of 1.6 and 2.1
      microM have been observed for glycerophosphoinositol 4-phosphate and
      glycerophosphoinositol 4-5-bisphosphate, respectively. The data indicate a
      bidirectional regulation of Na+/Ca2+ exchanger and suggest that phosphorylated
      glycerophosphoinositols can be regarded as novel signal transducers of
      intracellular Ca2+ regulation in heart cell.

PMID- 7826387
TI  - Molecular cloning of the human placental folate transporter.
AB  - We have isolated a cDNA clone from a human placental library which codes for a
      functional folate transporter (hFOLT). An RT-PCR product obtained from mouse
      intestinal mRNA using primers specific for the mouse folate transporter cDNA was
      used to screen the cDNA library. The hFOLT cDNA predicts a protein of 590 amino
      acids with twelve potential transmembrane domains. The amino acid sequence has
      65% identity to the mouse and hamster folate transporters. When transfected into
      COS-1 and HeLa cells, the hFOLT cDNA causes a significant increase in the uptake
      of 5-methyltetrahydrofolate. The mRNA transcripts hybridizing to the hFOLT cDNA
      are detectable in the placenta and liver and also in several cell lines of human
      origin. The size of the principal transcript is 2.7 kb. This constitutes the
      first report on the cloning of a vitamin transporter from a human tissue.

PMID- 7826388
TI  - The isomerization catalyzed by Brevibacterium sterolicum cholesterol oxidase
      proceeds stereospecifically with one base.
AB  - We have demonstrated that the isomerization reaction catalyzed by Brevibacterium
      sterolicum (ATCC 81387) cholesterol oxidase (EC 1.1.3.6) proceeds via a
      stereospecific proton transfer from the 4 beta carbon to the 6 beta carbon to
      form 4-cholestene-3-one using deuterated and nondueterated substrates. This
      result implies that there is one active site base, positioned over the beta-face,
      responsible for isomerization. On the basis of X-ray crystallographic evidence
      [Li, J., Vrielink, A., Brick, P. & Blow, D. M. Biochemistry 32, 11507-11515
      (1993)], glutamate-361 is the most likely candidate for this general base.

PMID- 7826389
TI  - Characterization of recombinant human interleukin 4 receptor from CHO cells: role
      of N-linked oligosaccharides.
AB  - Interleukin 4 (IL-4) mediates its biological activities through interaction with
      its receptor on the cell surface. A recombinant extracellular domain of the alpha
      subunit of human interleukin 4 receptor was expressed in CHO cells and purified
      to homogeneity by a combination of ion exchange and immunoaffinity
      chromatography. Analysis of the purified protein by MALDI MS provided an average
      mass of 38,241 Da while microsequencing identified the site of the signal
      sequence processing to be Ser23-Gly24. The receptor was highly glycosylated,
      containing N-linked complex oligosaccharides with bi-, tri-, and tetraantennary
      structures. Five of the six potential glycosylation sites could be assigned to
      Asn residues 53, 98, 128, 134 and 176. N-deglycosylation increased aggregation
      and reduced solubility of the receptor but did not affect its IL-4 binding
      activity. These observations provide preliminary insights into the role of N
      linked oligosaccharides in IL-4 receptor biosynthesis and function at the cell
      surface.

PMID- 7826390
TI  - Cyclic AMP is an essential factor in immune responses.
AB  - In the present studies, cAMP, a secondary messenger historically viewed as a
      negative mediator of immune responses, was demonstrated to possess
      immunoenhancing activity at low concentrations. In parallel experiments the
      adenylate cyclase inhibitor, 2',3'-dideoxyadenosine, produced a marked inhibition
      of humoral and proliferative immune responses suggesting that cAMP at
      physiologically relevant concentrations acts as a critical second messenger in
      immune responses. Direct addition of dibutyryl cAMP (10-100 microM), a membrane
      permeable cAMP analog, to mouse spleen cell cultures produced a marked and dose
      related increase (25-100%) in humoral immune responses as measured by the primary
      IgM antibody forming cell response to the antigen, sheep erythrocytes. Over a
      similar concentration range, dibutyryl cAMP (5-50 microM) also dose-dependently
      enhanced (25-50%) phorbol 12-myristate 13-acetate/ionomycin-stimulated
      lymphoproliferation. Incubation of spleen cells with 2',3'-dideoxyadenosine (40
      80 microM), an adenylate cyclase inhibitor, for 30 min depressed significantly
      the basal level of intracellular cAMP. 2',3'-dideoxyadenosine treatment also
      significantly decreased both the antibody forming cell response and the
      proliferative response in a dose-dependent manner. Interestingly, the antibody
      forming cell response exhibited significantly greater sensitivity to inhibition
      by 2',3'-dideoxyadenosine than the lymphoproliferative responses. The critical
      role for cAMP as a positive immunoregulatory signal is further supported by the
      fact that the immunosuppression by 2',3'-dideoxyadenosine could be reversed
      completely in the antibody forming cell response to sheep erythrocytes through
      the addition of dibutyryl cAMP into the culture medium. Partial but not complete
      reversal of the inhibitory effects of 2',3'-dideoxyadenosine on
      lymphoproliferation was also demonstrated by dibutyryl cAMP. Taken together,
      these results suggest that cAMP acts as a positive regulatory signal for immune
      responses as indicated by the fact that depletion of intracellular cAMP induces a
      marked inhibition of humoral and proliferative responses.

PMID- 7826392
TI  - Stabilization of secondary structure of Alzheimer beta-protein by aluminum(III)
      ions and D-Asp substitutions.
AB  - The CD spectra of the D-Asp substituted analogs of amyloid peptides, beta 6-25
      and beta 1-40, showed a distinct blue-shift on Al3+ complexation. The influence
      of Al3+ coordination was most significant on the triply substituted beta 1-40 (D
      Asp 1,7,23). This analog showed a reduction of the minima near 210nm and a
      simultaneous increase in the maxima near 200nm as compared to the native L-Asp
      beta 1-40. These observations suggest that Al3+ interaction with D-Asp induces
      the peptide backbone to increase its antiparallel beta-sheet character. D-Asp
      substitution and chelation by Al3+ lead to increased stability of higher
      molecular weight species of beta 1-40, and thereby could increase the toxicity of
      the Alzheimer amyloid protein.

PMID- 7826391
TI  - Localization of a critical diphtheria toxin-binding domain to the C-terminus of
      the mature heparin-binding EGF-like growth factor region of the diphtheria toxin
      receptor.
AB  - The monkey and human heparin-binding EGF-like growth factor precursors are
      diphtheria toxin receptors. To investigate which portion of this growth factor
      precursor is responsible for binding the toxin, the monkey precursor was compared
      to the mouse precursor which does not bind the toxin. Three clusters of differing
      residues were identified. The human mature growth factor (residues 63-148), which
      contains two of three differing clusters, inhibited the binding of radiolabeled
      toxin to cell-surface receptors, thus narrowing the binding domain to 86 of the
      208 residue precursor. To define further the binding domain, chimeric
      mouse/monkey precursors were expressed and assayed for toxin sensitivity. The
      third cluster, residues 122-135, was found to be the most important region for
      toxin binding. Total replacement of monkey residues with mouse residues N
      terminal to this region yields a highly toxin-sensitive cell. Collectively, the
      results suggest that the most critical residues for toxin binding lie between
      residues 122-148.

PMID- 7826393
TI  - Glutathione reductase and lipoamide dehydrogenase have opposite
      stereospecificities for alpha-lipoic acid enantiomers.
AB  - The reduction of exogenous alpha-lipoic acid to dihydrolipoate by mammalian cells
      and tissues confers additional antioxidant protection to the cell. Both (R+) and
      (S-) isomers of alpha-lipoic acid were analyzed as substrates with glutathione
      reductase from several sources and with mammalian lipoamide dehydrogenase.
      Mammalian glutathione reductase catalyzed faster reduction of (S)-lipoic acid
      (1.4-2.4-fold greater activity) than of (R)-lipoic acid, whereas lipoamide
      dehydrogenase had a very marked preference for (R)-lipoic acid (18-fold greater
      activity) over (S)-lipoic acid. Mammalian glutathione reductase showed better
      affinity for (S)-lipoic acid substrate; Km values were 3.5 mM for (S)-lipoic acid
      and and 7 mM for (R)-lipoic acid. Glutathione reductase from yeast reduced lipoic
      acid less efficiently than the mammalian enymes, had a Km for both stereoisomers
      of about 10 mM, and showed little stereospecificity. Although (S)-lipoic acid is
      not formed in nature, these findings indicate that exogenous (S)-lipoic acid may
      have a useful role as an antioxidant for mammalian systems.

PMID- 7826394
TI  - Mass spectrometric determination of the radical scission site in the anaerobic
      ribonucleotide reductase of Escherichia coli.
AB  - Active anaerobic ribonucleotide reductase from Escherichia coli contains an
      oxygen sensitive organic radical, proposed to reside on glycine-681 at the C
      terminal end of the polypeptide chain. Exposure of the radical containing enzyme
      to oxygen results in cleavage of the molecule at the site of the hypothetical
      radical. We determined by mass spectrometry the size of the complete and the C
      terminal-processed polypeptides. The difference in size between the two molecules
      shows that cleavage occurs at the N-terminal side of glycine-681, demonstrating
      that the organic radical is indeed located on this amino acid residue.

PMID- 7826395
TI  - The pH-dependence of the equilibrium between the fast- and slow-folding forms of
      bovine prothrombin fragment 1: a role for pH-induced self-association?
AB  - Examination of the pH- and ionic strength (mu)-dependence of the equilibrium
      between fast- and slow-folding forms of bovine prothrombin fragment 1 reveals a
      sharp dependence of Keq ([% fast-folding form]/[% slow-folding form]) and %
      fluorescence quenching (%Q) on pH at low mu, and the absence of a pH-dependence
      of Keq at high mu (0.1 M NaCl) and much reduced pH-dependence of %Q, suggesting
      that the ionization process is coupled to other processes, such as self
      association. The observed low mu pH effect on Keq amounts to a 10% increase in
      the % of the fast-folding form of prothrombin at low pH. We hypothesize the
      existence of a pH-dependent self-association of bovine prothrombin fragment 1.
      This process is associated with a conformation change involving an ionizing group
      with pKa in the neighborhood of 6.5 and a change in Keq from 0.27 to 0.45.

PMID- 7826396
TI  - Reversible conjugation of isothiocyanates with glutathione catalyzed by human
      glutathione transferases.
AB  - Rates were determined for the nonezymatic (second order rate constants) and
      enzyme-catalyzed conjugations with glutathione of four isothiocyanates that are
      present in edible plants (allyl-, benzyl-, phenethyl-isothiocyanates, and
      sulforaphane). Of four cloned human glutathione transferases studied, GSTP1-1 and
      GSTM1-1 were the most efficient catalysts. GSTA1-1 was less efficient, and GSTM2
      2 was the least efficient. Conjugation of benzyl-NCS is the most rapid and that
      of sulforaphane [CH3S(O)(CH2)4-NCS] is the slowest. The large enzymatic rate
      enhancements and the abundance of the enzymes suggest that the glutathione
      transferases play important roles in the metabolic disposition of isothiocyanates
      in humans. Enzymatic cleavage of the GSH conjugates of isothiocyanates
      (dithiocarbamates) is catalyzed by glutathione transferases. The importance of
      these reverse reactions is probably limited because they are slow and inhibited
      by high intracellular concentrations of glutathione.

PMID- 7826397
TI  - Nature and transcriptional role of catalytic subunits of yeast mitochondrial cAMP
      dependent protein kinase.
AB  - We have shown that mitochondrial (mt) transcription in yeast (S. cerevisiae) is
      governed in part by cAMP via a mt cAMP-dependent protein kinase (cAPK), and that
      the BCY1 gene product acts as regulatory subunit for that organellar enzyme, as
      it does for cytoplasmic cAPK. Here we assess mt cAPK activity and mt
      transcription in mutants for the TPK1, TPK2, and TPK3 genes, which encode
      catalytic subunits of cytoplasmic cAPK. Protein extracts from purified
      mitochondria from each of the three possible double TPK mutants show mt cAMP
      dependent protein phosphorylation. Relative mt transcript levels in these
      mutants, however, suggest that TPK2 functions less well than does TPK1 or TPK3 in
      organellar transcriptional control. Thus, both mt and cytoplasmic cAPKs employ
      the same species of regulatory and catalytic proteins, and versions of the enzyme
      having various combinations of catalytic species function differentially in cAMP
      dependent mt transcriptional control.

PMID- 7826398
TI  - Identification of a brain- and reproductive-organs-specific gene responsive to
      DNA damage and retinoic acid.
AB  - We have identified and sequenced a new gene from human cells that is responsive
      to DNA damage and retinoic acid treatment, and it is highly expressed in brain
      and reproductive organs (BRE). This BRE gene encodes an mRNA of 1.7-1.9 kb, with
      an open reading frame of 1,149 bp, and gives rise to a deduced polypeptide of 383
      amino acid residues. Treatment of fibroblast cell with UV and 4-nitroquinoline-1
      oxide caused more than 90% and 50% decreases in BRE mRNA, respectively. Similar
      decreases in BRE expression were observed in RA-treatment of the brain glioma
      cell U-251 and the promyelocytic cell HL-60. Decrease in BRE mRNA was also
      observed in a squamous carcinoma cell, 1483, that showed X-ray resistance and has
      a more aggressive tumorigenic phenotype, but BRE expression was unchanged in
      cells after growth inhibition. These data indicate that BRE is a house-keeping
      gene and it may play a role in homeostatis or in certain pathways of
      differentiation in cells of neural, epithelial and germ line origins.

PMID- 7826399
TI  - Oscillation of inositol polyphosphates in the embryonic cleavage cycle of the
      Xenopus laevis.
AB  - Evidence suggests that a transient increase in intracellular calcium ([Ca2+]i) is
      an important modulator during the cell division cycle in early embryos. We have
      recently shown that inhibition of Ins(1,4,5)P3-induced Ca2+ release in the
      cleaving Xenopus embryos greatly lengthens the cell cycle duration. In this
      report, we have directly measured the changes of Ins(1,4,5)P3 content during the
      first two cleavage cycles in the Xenopus embryos. HPLC profiles of cell extracts
      from dividing embryos show oscillations of inositol polyphosphates throughout the
      cleavage cycle with a transient production of Ins(1,4,5)P3 by the time of
      cleavage furrow completion. In addition, cyclic changes in inositol
      phospholipids, phosphatidylinositol 4,5-bisphosphate (PIP2) and
      phosphatidylinositol 4-phosphate (PIP) were detected during the cleavage cycle.
      These data strongly suggest the involvement of PIP2 turnover and periodic
      increase in Ins(1,4,5)P3 triggers [Ca2+]i transients during the early embryonic
      cell cycle in the Xenopus.

PMID- 7826400
TI  - Can an X-ray dose threshold be measured for the induction of SOS repair activity
      in E. coli.
AB  - Survival ("clonogenic ability") and induced DNA repair (SOS repair) have been
      studied at low X-ray doses in two Escherichia coli strains (GE94 and KY943), both
      of which contain a recA-lacZ protein fusion. X-ray doses greater than about 0.5
      Gray clearly induce SOS repair activity. However, the threshold dose that just
      activates SOS repair is probably much lower than 0.5 Gray, perhaps as low as
      0.001 Gray. It seems unlikely that this dose threshold can be more accurately
      measured with the recA-lacZ fusion technique.

PMID- 7826401
TI  - Magnesium ions but not ATP inhibit cyclic ADP-ribose-induced calcium release.
AB  - The pharmacology of the cyclic ADP-ribose (cADPR)-dependent Ca2+ release
      mechanism is very similar to that of the ryanodine receptor (RyR). Here we showed
      that MgCl2, a known inhibitor of RyR, blocked cADPR-induced Ca+2 release in sea
      urchin egg homogenates with a half maximal concentration of about 2.5 mM. The
      effect was specific since up to 10 mM Mg+2 had no effect on the Ca+2 release
      induced by inositol trisphosphate. K2ATP, another known modulator of RyR, at up
      to 10 mM did not affect the half-maximal concentration of cADPR, which remained
      at about 96 nM. These results indicate cADPR is a specific Ca+2 release activator
      and not merely an adenine nucleotide acting on the ATP-site. The inhibitory
      effects of Mg+2 further demonstrate the similarity between RyR and the cADPR
      dependent Ca+2 release system.

PMID- 7826402
TI  - Cell-binding and growth-stimulating activities of the C-terminal part of human
      MGSA/Gro alpha.
AB  - The FITC-labeled C-terminal alpha-helix portion of human MGSA/gro alpha (MGSA 47
      71) was shown, using flow cytometry, to bind to human melanoma cells Hs294t but
      not to non-melanoma cells. MGSA (47-71) is capable to induce specifically DNA
      synthesis of melanoma cells. These results indicate that the C-terminal portion
      of human MGSA is sufficient for its biological activity, thus raising questions
      about the importance of dimerization and of the N-terminal ELR box of the
      molecule which has been proposed.

PMID- 7826403
TI  - Cytosolic localization of beta 3-subunit of heterotrimeric GTP binding protein in
      rat hearts.
AB  - The expression of three different subtypes of GTP binding protein beta-subunits
      (beta 1, beta 2 and beta 3) was examined in rat hearts at both mRNA and protein
      levels. Among three subtypes, beta 3 mRNA was more abundant in ventricles while
      beta 1 and beta 2 mRNAs were expressed ubiquitously among ventricles, atria and
      aortas. The immunodetectable beta 1- and beta 3-proteins were predominantly found
      in the cytosolic fraction of rat ventricles. In this study, we demonstrate
      ventricle-specific expression of beta 3-subunit and localization of G protein
      beta 3-subunit in the cytosol of rat hearts. This unusual cytosolic localization
      of G protein beta 3-subunit might indicate subtype-specific function of G protein
      beta (gamma)-subunits in rat hearts.

PMID- 7826404
TI  - [Lipid peroxidation and mechanism of antioxidant effect of vitamin E].
AB  - Data concerning lipid peroxidation and mechanism of the vitamin E inhibiting
      action are reviewed. Steps of initiated lipid autooxidation, formation of primary
      and secondary oxidation products, destabilizing the membrane structure and
      possessing cytotoxic effects are described. The mechanism of the antioxidant
      action of alpha-tocopherol, dependence of its activity on the structure and
      composition of the products of cooxidation of lipids and alpha-tocopherol in
      biological and model systems are also discussed.

PMID- 7826405
TI  - [Structure of peptide fragments of the complex (Lys(Abz)26) neurotoxin II from
      Naja naja oxiana cross-linked with the nicotinic acetylcholine receptor from
      Torpedo californica].
AB  - After irradiating the acetylcholine receptor complex with the title neurotoxin
      derivative, the labeled delta-subunit was separated by preparative SDS-PAGE,
      reduced-carboxymethylated and cleaved with LysC endoproteinase. One of the
      radioactive peptides isolated by HPLC was further purified by electrophoresis in
      a tricin gel. Edman degradation of the radioactive fractions yielded the sequence
      of the delta-subunit fragment starting from Phe148. The AspN-cleavage of the
      radioactive peptide from the LysC digest gave on HPLC a radioactive peak which
      eluted similarly to peptide 33-44 generated by LysC/AspN-cleavage of 125I
      neurotoxin II. In model experiments, irradiation of the photoactivable derivative
      was found to produce a heterogeneous mixture of reaction products. Unusually low
      initial and repetitive yields were observed for neurotoxin II and its fragments
      containing the photolabeled and radiolabeled residues. These results might
      explain why the neurotoxin sequence was not detected on Edman degradation of the
      cross-linked products available at a low picomole level.

PMID- 7826406
TI  - [Synthesis and comparative analysis of antigenic activity of peptides from
      hypervariable region V3 of human immunodeficiency virus I gp120 surface
      glycoprotein].
AB  - A set of peptides (amino acid positions 10-23) corresponding to seven most widely
      spread variants of the gp120 V3 domain in the HIV-infected population of South
      Russia were prepared by the solid-phase synthesis. A laboratory variant of the
      indirect enzyme-linked immunosorbent assay (ELISA) was developed for the
      determination of V3 specific antibodies with use of the peptides synthesized. The
      analysis of the V3-specific antibodies in HIV-infected using the elaborated test
      system revealed a correlation between the V3 variants distribution and the
      occurrence of antibodies against these variants.

PMID- 7826407
TI  - [Genetic engineering of human insulin. IV. Development and optimization of an
      analysis system using reversed phase high pressure liquid chromatography].
AB  - The effectiveness of the RP HPLC application for the step-by-step analysis of the
      recombinant insulin production was studied. Properties of a number of commercial
      and experimental columns in different chromatographic conditions were considered.
      A three-dimension optimization of selectivity and resolution versus pH and ion
      strength was carried out. A mechanism of the resolution and selectivity control
      is suggested.

PMID- 7826408
TI  - [4'-Branched nucleosides. II. Synthesis of 4'-hydroxymethyl derivatives of 2',3'
      anhydronucleosides of the ribo- and lyxo-series].
AB  - A general synthetic method for 4'-hydroxymethyl-2',3'-anhydronucleosides from 1,2
      O-isopropylidene-4-hydroxymethyl-alpha-D-xylofuranose is described. The
      condensation of 1,2-di-O-acetyl-3-O-methanesulphonyl-4-benzoyloxymethyl-5-O-
      benzoyl-D-xylofuranose with trimethylsilyl derivatives of N6-benzoyladenine and
      N2-palmitoylguanine in the presence of stannic chloride resulted in the
      corresponding nucleosides. After their treatment with NH4OH-EtOH, corresponding
      2',3'-riboanhydronucleosides were isolated. Condensation of 1,2-di-O-acetyl-3-O
      benzoyl-4-benzoyloxymethyl-5-O-benzoyl-D-xy lofuranose with trimethylsilyl
      derivatives of purines followed by selective deacetylation led to the nucleosides
      with free 2'-OH group. Their 2'-O-mesylation and epoxidering closure resulted in
      the isolation of 2',3'-anhydrolyxonucleosides with 38-44% yields. All the
      compounds synthesized did not inhibit HIV-1 reproduction in human H9 and PBL cell
      cultures nor HSV-2 and HCMV reproduction in vero cells up to 100 microM
      concentrations.

PMID- 7826409
TI  - [Structure of carbohydrate chains of molecular forms of alpha1-acidic
      glycoprotein from ascitic fluid from patients with stomach cancer].
AB  - The immunochemically pure alpha 1-acid glycoprotein (aAGP) from ascitic fluid of
      patients with stomach cancer was separated by chromatography on Con A-Sepharose
      into Con A-nonbound (aAGP-1, 43, 5 kDa, 70%) and Con A-bound (aAGP-2, 41.5 kDa,
      24% and aAGP-3, 40.0 kDa, 5%) forms, differing in the monosaccharide composition.
      Comparative study of structures of their N-carbohydrate chains with the aid of
      the HPLC of fluorescence-labelled oligosaccharides showed that the molecular
      forms differ by the ratio of the di-, tri-, and tetraantennary carbohydrate N
      chains of a complex type. The molecular forms of aAGP differ from nAGP by amounts
      of Le(x)-fragments and agalacto-oligosaccharides.

PMID- 7826410
TI  - [New acetylcholinesterase inhibitors--derivatives of vitamin B6].
AB  - A new approach to design of reversible inhibitors of acetylcholinesterase (ACHE)-
      derivatives of natural compounds--has been worked out, as exemplified by vitamins
      of the B6 group. Analysis of the data obtained revealed main structural elements
      of the 3-hydroxypyridine molecule related to the inhibitory properties.
      Pyridoxamine derivatives are of interest in constructing new potent inhibitors of
      ACHE.

PMID- 7826411
TI  - [Synthesis and study of NMR spectra and conformations of branched
      oligosaccharides. 2,3-di-O-glycosylated methyl-alpha-L-rhamnopyranosides with one
      or two 2-acetamido-2-deoxy-beta-D-glucopyranosyl residues].
AB  - A series of methyl 2,3-di-O-glycosyl-alpha-L-rhamnopyranosides with 2-acetamido-2
      deoxy-beta-D-glucopyranosyl substituents have been synthesized and the deviations
      from additivity (delta delta) in their 13C-NMR spectra determined. It is shown
      that the delta delta values for the trisaccharides with the GlcNAc substituent at
      O-2 of the diglycosylated Rha may markedly differ from the delta delta values in
      the spectra of the respective trisaccharides with the Glc substituent. These
      deviations are probably associated with the intramolecular spatial interactions
      with participation of the NHAc-group.

PMID- 7826412
TI  - [Oligonucleotide-directed mutagenesis of inhibitory gamma-subunits of cGMP
      phosphodiesterase from bovine outer rod segments. A new hypothesis on mechanisms
      for inhibiting catalytic subunits by gamma-subunits and activation of a
      holoenzyme by transducin].
AB  - Two mutants of the phosphodiesterase (PDE) gamma subunit (PDE gamma) from bovine
      retinal rods were synthesized by sequential transcription and translation in
      vitro. PDE gamma mutants R24E and H79L exhibited inhibitory properties similar to
      those of the wild-type PDE gamma (wtPDE gamma). At the same time, affinity to the
      rod outer segment (ROS) membranes is lower for R24E and higher for H79L in
      comparison with wtPDE gamma. The transducin alpha subunit (in a complex with the
      GTP non-hydrolyzable analogue, GTP gamma S) activates the trypsin-treated PDE
      (tPDE) inhibited by wtPDE gamma weaker than tPDE inhibited by R24E and stronger
      than tPDE inhibited by H79L. To explain the properties of these and earlier
      studied PDE gamma mutants, a new hypothesis on the mechanisms of inhibition of
      the PDE catalytic subunit dimer (PDE alpha beta) by PDE gamma and mechanism of
      the PDE holoenzyme (PDE alpha beta gamma 2) activation by the transducin alpha
      subunit in a complex with GTP (T alpha.GTP) is proposed: 1) two sites on PDE
      alpha beta for the PDE gamma binding (A- and the B-site) are different in
      structure. Sites on PDE gamma interacting with A- and the B-sites on PDE alpha
      beta are also different in structure. The site on PDE gamma interacting with the
      B-site partially overlaps with the T alpha.GTP binding site; 2) PDE gamma bound
      to the B-site provides the main contribution to inhibition of the enzyme
      catalytic activity; 3) T alpha.GTP first interacts with the PDE gamma bound to
      the A-site in the PDE holoenzyme and removes this PDE gamma in a PDE gamma.(T
      alpha.GTP) complex. This results in a slight increase of the catalytic activity
      of the PDE alpha beta gamma complex remaining bound to the ROS membranes; 4)
      after removal of PDE gamma from the A-site, another T alpha.GTP molecule is
      enabled to interact with both PDE alpha beta and PDE gamma bound to the B-site on
      PDE alpha beta. This interaction results in the formation of a ROS membrane-bound
      fully catalytically active triple complex PDE alpha beta.PDE gamma.(T alpha.GTP).

PMID- 7826413
TI  - [Structure-activity study of the basic toxic component of venom from the ant
      Ectatomma tuberculatum].
AB  - A toxic principle of the Ectatomma tuberculatum ant venom called ectatomin was
      isolated. Ectatomin is a protein with molecular weight 7928 Da. Its complete
      amino acid sequence and spatial structure in aqueous solution were determined by
      protein chemistry methods and NMR spectroscopy techniques. Ectatomin contains two
      highly homologous polypeptide chains linked to each other by a disulfide bond.
      The chains consist of 37 and 34 amino acid residues with an internal disulfide
      bridge in each. In aqueous solution the molecule forms a bundle of four
      amphipathic alpha-helices. This toxin in a concentration of 0.05-0.01 mM forms
      potential dependent nonselective cation channels both in cell and artificial
      membranes. The channel is dimeric and the mechanism of its formation can be
      explained in terms of the spatial structure established.

PMID- 7826414
TI  - [Structure-activity domain of elongation factor EF-2. Analysis of fragments of
      limited EF-2 hydrolysis, obtained using trypsin and elastase].
AB  - Limited hydrolysis of EF-2 with trypsin in mild conditions leads to cleavage at
      the N-terminal part of the protein, at the region of phosphorylation, at the
      Arg54 and Arg65 residues. The trypsinolysis product, fragment T1', containing
      Thr56 and Thr58, which are phosphorylated in EF-2, is also phosphorylated by EF-2
      kinase at the same residues. In the phosphorylated EF-2, digestion by trypsin
      takes place only at Arg65, resulting in a reduction of the rate of hydrolysis in
      comparison with the native EF-2. Digestion of EF-2 with elastase results in the
      formation of two fragments E1 and E2 (60 and 40 kDa, respectively). Fragment E1
      represents the N-terminal part of EF-2. It is resistant to the further action of
      elastase, is not cleaved by trypsin, and loses its capability for
      phosphorylation. Fragment E2, the C-end part of the molecule, is not resistant to
      the further action of elastase and retains its capability for ADP-ribosylation
      with the A fragment of diptheria toxin and NAD+. Electrophoretic analysis of EF-2
      and its proteolytic fragments according to O'Farrell showed that the
      modification, resulting in the presence of two initial forms of EF-2, is located
      between the amino acid residues 66 and 506 of the polypeptide chain. In
      conclusion a possibility of studying the formation of partial functional
      activities within the framework of individual structure-functional domains using
      a set of N-terminal fragments of various length is discussed.

PMID- 7826415
TI  - [Enteropeptidase and its use for cleavage of chimeric proteins].
AB  - Cleavage of different chimeric proteins after specific linker (Asp)4Lys by the
      highly purified enteropeptidase was investigated, proteins being were accumulated
      in inclusion bodies or secreted from the cell. Kinetic constants for enzymatic
      hydrolysis were obtained, indicating that the substrate binding depended mainly
      on the affinity to the linker peptide (Asp)4Lys. Conditions for the efficient
      cleavage of recombinant proteins with enteropeptidase are formulated.

PMID- 7826416
TI  - [Separation of recombinant proteins by chromatography on vesicular sorbents].
AB  - Vesicle chromatography, a recently developed method for separation of
      biomolecules, uses the vesicular packing (VP) material (clusters of microcapsules
      derived from plant cells), which was tested with respect to its application for
      the recombinant protein separation. Since VP has a well-defined separation limit,
      biomolecules are distributed in two separate peaks: large molecules are excluded
      and small molecules permeate through cell walls into the empty cell lumen.
      Recombinant proteins frequently form oligomers, which differ from monomers not
      only in size but also chemically and biologically. In the present study,
      separations of the recombinant proinsulin fusion protein oligomer and monomer,
      the recombinant human gamma-interferon monomer and dimer and recombinant tumour
      necrosis factor-alpha were investigated. For peak identification, the fractions
      and starting samples of the recombinant proteins were analysed by HPLC. The
      separations occurred without any sorption effects and with high efficiency and
      resolution of the protein peaks at a short column (10 cm). The VP is
      characterised by a high load ability, which favours the scale-up purification of
      the recombinant proteins. The combination of VP and HPLC is a considerable
      advance in biotechnology separation.

PMID- 7826418
TI  - [Quantitative characteristics of modifying nucleic acids by alkylating
      oligonucleotide derivatives in the presence of oligonucleotide effectors].
AB  - Modification of the 26-meric DNA fragment d(TTGCCTTGAATGGGAAGAGGGTCATT) with 4-(N
      2-chloroethyl-N-methylamino)benzyl-5'-phosphamide derivative of
      hexadeoxyribonucleotide d(pTTCCCA) was investigated in the presence of two bis
      3',5-N-(2-hydroxyethyl)phenazinium derivatives of octadeoxyribonucleotides
      (effectors E1 and E2) forming complementary complexes with the target next to 3'-
      and 5'-ends of the reagent's recognition site, respectively. In the absence of
      effectors, G17 is predominantly modified. Some minor modification of G12, G13 and
      G14 was also observed. The association constant of the target with the reagent
      was calculated using the dependence of the modification extent on the initial
      concentration of the reagent and was found to be Kx = (2.16 +/- 0.38) x 10(4) M-1
      at 25 degrees C. At the reagent concentration 5 x 10(-6) M the target
      modification was nearly absent. In the presence of E1 the modification extent of
      the 26-mer increased with its concentration to a plateau value of approximately
      0.5. Quantitative treatment of this concentration dependence permitted to
      estimate the value of the product Ke1 alpha = (3.95 +/- 0.43) x 10(8) M-1, where
      alpha 1 is the cooperativity coefficient and Ke1 is the association constant of
      the target with E1. To determine alpha 1, the Ke1 value was measured by the gel
      retardation method and found to be (5.06 +/- 0.23) x 10(7) M-1. Consequently,
      alpha 1 approximately 8. Effector E2 is less efficient and permits to reach the
      plateau value only as low as 0.24. This may be due to the competition of the
      reagent and E2 for the reagent recognition site, since the latter is partially
      complementary to this site. The increase of the E2 concentration results in a
      decrease of the modification extent of G17 accompanied with an increase of the
      modification extent of G12-G14. Thus, in the conditions used the oligonucleotide
      effectors although increasing the duplex stability do not permit to achieve
      quantitative yields as it should be for reactions proceeding in quasi-equilibrium
      conditions.

PMID- 7826417
TI  - [Biologically active peptides isolated from the brain of hibernating ground
      squirrels].
AB  - More than 20 peptides have been isolated and sequenced from the brain of
      hibernating ground squirrel Citellus undulatus. Some of the isolated peptides
      were chemically synthesized and investigated for the spectrum of biological
      activity. One of the isolated peptides, neokyotorphin (Thr-Ser-Lys-Tyr-Arg),
      earlier known as a weak analgetic, is found to have a cardiotropic and
      thermoregulatory activity. Neokyotorphin activates in vitro voltage-dependent
      calcium and blocks ATP-dependent potassium currents in the frog atrial fibres.
      Intraperitoneal injection of this peptide in hibernating ground squirrels speeds
      up the arousal of animals increasing sharply the heart rate and oxygen
      consumption. Intraperitoneal and intranasal administrations of neokyotorphin in
      rats raises body temperature in thermoneutral conditions (26-28 degrees C)
      exerting no effects at low (4-6 degrees C) and high (31-32 degrees C)
      environmental temperatures. Another isolated peptide, Asp-Tyr, blocks the inward
      voltage-dependent calcium current in the frog atrial fibres and slightly
      increases the outward potassium current. Sulfated analogue of this dipeptide
      (aspartyl-O-sulfate-tyrosine) more effectively blocks the inward voltage
      dependent calcium current in the frog atrial fibres and have no effects on the
      outward potassium current.

PMID- 7826419
TI  - [Synthesis and prokaryotic expression of the gene for the human interleukin-1
      receptor antagonist].

PMID- 7826420
TI  - [Selectively cleaved synthetic oligodeoxyribonucleotides for reverse
      immobilization of DNA].
AB  - A streptavidin-coated TSK-gel support, with the loading capacity of 50-70 nmol of
      biotinylated substance per gram of dry support, and biotinylated
      oligonucleotides, containing the 4,9-dithiadodecane-6,7-dihydroxy-1,12
      diphosphate insert, were prepared for the reversible immobilization of DNA. A non
      nucleotide link can be located either at 5'- or 3'-end of the DNA fragment
      between the biotin moiety and the nucleotide sequence and is subjected to the
      selective periodate cleavage at the glycol group, which takes 45 min in solution
      and 3 h in heterophase. For the incorporation of the cleavable and biotin
      moieties into synthetic oligonucleotides, the corresponding phosphoramidite
      reagents and biotinylated CPG support were synthesized.

PMID- 7826421
TI  - [Oligodeoxyribonucleotides containing 1-(beta-D-3'-deoxy-threo
      pentofuranosyl)pyrimidine chains].
AB  - Effective methods of multiple incorporations of nucleotides with the inverted
      configuration of C2' hydroxyl group have been developed. The presence of tU and
      tC as 3'-terminal oligonucleotide modifications is shown to increase their
      resistance to snake venom phosphodiesterase. The obtained compounds are promising
      for the use in antisense biotechnology.

PMID- 7826422
TI  - [Isolation and general characteristics of lectin from the ascidian Didemnum
      ternatum].
AB  - DTL was isolated from the Didemnum ternatum colonial ascidian and purified by
      affinity chromatography on cross-linked ovalbumin followed by gel-filtration on
      Sephadex G-100. SDS-PAGE of the preparation showed a major intense band with a
      relative mol. wt. of ca. 27 kDa. In the presence of 2-mercaptoethanol, DTL gave
      rise to a single band of 10 kDa. The lectin isolated was found to agglutinate
      Ehrlich's carcinoma cells and trypsinized human A, B, O erythrocytes, the
      hemagglutination being inhibited by GlcNAc, chitobiose, desialylated
      glycoproteins. Comparison of the sugar moieties of the glycoproteins used as
      inhibitors led to suggestion that the specific sugar binding site contains, as a
      dominant sugar, a "bisecting" glucosamine attached through a beta-1,4-linkage to
      the beta-linked mannose residue of N-glycosidic chains of a complex or hybrid
      type. An absence of sialic acid residues linked with galactose residues appeared
      to be necessary for binding DTL with the complex-type sugar chains. DTL inhibits
      proliferation and reduces DNA biosynthesis ([3H]thymidine incorporation) in
      tumour cells (HeLa). Principal morphological differences were detected to occur
      between intact and DTL-treated HeLa cells.

PMID- 7826424
TI  - Managing sympathetic blockade in the postanesthesia care unit: a case report.
AB  - Based on the content of this article, the reader should be able to (1) discuss
      the significance of differential blockade on postanesthesia nursing assessment;
      (2) compare the zones of differential blockade between spinal and epidural
      anesthesia; (3) state the physiological response to preload caused by sympathetic
      blockade; (4) assess sympathetic blockade using a dermatome figure; and (5) state
      three interventions used to manage sympathetic blockade.

PMID- 7826423
TI  - [Conjugates and carbohydrate chains of alpha 1-acid glycoprotein with
      polyacrylamide maintain the immunomodulating activity of native glycoprotein].
AB  - Translocation of carbohydrate glycoprotein N-chains onto soluble polyacrylamide
      was proposed as a method for studying the biological role of carbohydrate chains.
      N-linked carbohydrate chains of alpha 1-acid glycoprotein (AGP) were aminated at
      the reducing GlcNAc moiety and covalently attached to polyacrylamide (PAA). Thus
      "pseudo-AGP" was obtained where peptide core was replaced with PAA. The synthetic
      model mimics AGP by M(r) and carbohydrate content as well as the ratio of tetra-,
      tri- and diantennary and mono-, di-, tri- and tetrasialo chains. It was shown
      that the conjugate inhibits proliferation of lymphocytes like the parent AGP.
      Therefore, the property of AGP to inhibit the lymphocyte proliferation is
      attributed to its carbohydrate chains, whereas peptide core serves as carrier
      providing polyvalent interaction of multiple carbohydrate chains with cell.

PMID- 7826425
TI  - Immunotoxins: is there a clinical value?
AB  - Drug targeting is an attractive new approach to killing malignant cells, thereby
      leaving normal tissue unharmed. A decisive breakthrough was the advent of
      hybridoma technology, making monoclonal antibodies (MoAb) available in limitless
      supply. To construct reagents with selectivity for certain tumor cells, MoAbs or
      Fab' fragments were chemically linked to ribosome-damaging toxins derived from
      plants or bacteria like ricin, abrin, saporin, Pseudomonas exotoxin (PE), and
      diphtheria toxin (DT) to form immunotoxins, which combined the selectivity of the
      carrier moiety with the potency of the toxin moiety. The first generation of
      these immunotoxins showed impressive results in vitro but in most cases
      disappointing antitumour effects in animals or humans. By contrast, the second
      generation of immunotoxins, consisting of either A chain immunotoxins with a
      greatly improved stability in vivo or so-called 'blocked' ricin immunotoxins,
      have been demonstrated to be extremely effective in several animal models.
      Preliminary results of the current clinical trials suggest a possible clinical
      use of immunotoxins in leukemia and lymphoma patients. Genetically engineered
      fusion toxins have become available, which consist of a growth factor or a
      cytokine fused to a toxin moiety. In this paper, we will review the features of
      the three groups of immunotoxins which are most frequently used, i.e., ricin A
      chain and similar immunotoxins, blocked ricin immunotoxins, and recombinant
      toxins constructed with Pseudomonas exotoxin or diphtheria toxin.

PMID- 7826426
TI  - Global public health and the information superhighway.

PMID- 7826427
TI  - Evaluation of interhospital spread of methicillin-resistant Staphylococcus aureus
      in Sao Paulo, Brazil, using pulsed-field gel electrophoresis of chromosomal DNA.
AB  - To evaluate the interhospital spread of methicillin-resistant Staphylococcus
      aureus (MRSA) clone in Sao Paulo, we analyzed the restriction fragment length
      polymorphisms (RFLP) of chromosomal DNA from isolates from nine Sao Paulo
      hospitals. Restriction digestion of genomic DNA was performed with SmaI and the
      fragments were separated by pulsed-field gel electrophoresis. Only six different
      RFLP patterns were demonstrated among 30 MRSA isolates. Isolates possessing an
      identical RFLP pattern were demonstrated in eight of the nine Sao Paulo hospitals
      evaluated. Our results documented the widespread dissemination of a single clone
      of MRSA in several hospitals. Furthermore, the small clonal variability among
      multidrug-resistant MRSA coupled with the wide spread of this clone could make
      the intrahospital epidemiological evaluation of RMSA outbreaks very difficult.

PMID- 7826428
TI  - Inclusion of women in AIDS clinical research: a political and legal analysis.
AB  - Thirteen years into a devastating epidemic that is having a serious impact on
      women of color, we are only a few steps closer to genuine participation by women
      in AIDS clinical trials. Those who depend most heavily on research settings not
      only for the promise of an accessible cure, but also for life-prolonging
      therapies and state-of-the-art medical care are hurt most by exclusionary
      policies. Restrictive and contradictory federal policies, pharmaceutical company
      reluctance to complete animal toxicology and reproductive studies, inadequate
      informed consent, and unfounded industry fear of liability all play a part in
      keeping women with AIDS from participating in clinical research.

PMID- 7826429
TI  - Increased risk of Alzheimer's disease in mothers of adults with Down's syndrome.

PMID- 7826430
TI  - Alabama sports medicine experience with isolated and combined posterior cruciate
      ligament injuries.
AB  - Injuries to the posterior cruciate ligament (PCL) are an uncommon but significant
      instability pattern that eventually deteriorates the articular surface of the PLC
      deficient knee. Although controversy persists regarding the appropriate treatment
      for the isolated PCL tear, patients with combined ligament injuries are best
      served by reconstruction of the PCL and surgical correction of the other injured
      tissues. The authors outline their experience with these complex ligamentous
      derangements.

PMID- 7826431
TI  - Immediate physiological responses of healthy volunteers to different types of
      music: cardiovascular, hormonal and mental changes.
AB  - A group of 20 healthy volunteers [10 women, 10 men; median age 25 (20-33) years]
      were examined by means of pulsed wave Doppler echocardiography, blood sample
      analysis and psychological testing before and after listening to three different
      examples of music: a waltz by J. Strauss, a modern classic by H. W. Henze, and
      meditative music by R. Shankar. To assess small haemodynamic changes, mitral
      flow, which reflects left ventricular diastolic behaviour, was measured by
      Doppler ultrasound. Heart rate, arterial blood pressure and plasma concentrations
      of adrenocorticotropic hormone, cortisol, prolactin, adrenaline, noradrenaline,
      atrial natriuretic peptide (ANP) and tissue plasminogen activator (t-PA) were
      determined simultaneously. Transmitral flow profile is characterized by early E
      wave and late atrial induced A-wave. Velocity-time integrals were measured and
      the atrial filling fraction was calculated. The mental state was measured by
      using a psychological score (Zerssen) with low values (minimum 0) for
      enthusiastic and high values (maximum 56) for depressive patterns. Music by J.
      Strauss resulted in an increase of atrial filling fraction (AFF; 29% vs 26%; P <
      0.05) and ANP (63 pg.ml-1 vs 60 pg.ml-1; P < 0.05). The mental state was improved
      (Zerssen: 6.5 vs 11 points; P < 0.05). After the music of H. W. Henze prolactin
      values were lowered (7.7 ng.ml-1 vs 9.1 ng.ml-1; P < 0.01).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7826432
TI  - Identification of mitochondrial respiratory proteins from the green alga
      Chlamydomonas reinhardtii.
AB  - Membrane preparations from the green alga Chlamydomonas reinhardtii contain both
      thylakoid and mitochondrial membranes [1]. These preparations have been intensely
      used to study the structure, function and biogenesis of protein complexes
      involved in the photosynthetic pathway. We show here that these preparations are
      also suitable for studying protein complexes of the mitochondrial respiratory
      chain of the alga. The respiratory complexes, fractionated on a sucrose gradient
      in the presence of Triton X-100, were identified by their catalytic properties
      and their polypeptide content. From the bottom to the top of the sucrose
      gradient, we identified the NADH: ubiquinone oxidoreductase (complex I), the
      mitochondrial ATP synthase (F0F1-ATPase), the cytochrome bc1 complex and the
      cytochrome c oxidase. At the top of the gradient, another enzyme was detected
      which displayed an NADH: menaquinone oxidoreductase activity.

PMID- 7826434
TI  - Noncognitive factors and performance predictions.

PMID- 7826433
TI  - Need for more career counseling.

PMID- 7826435
TI  - Faculty development in a changing academic environment.
AB  - Faculty development--thought of not merely as improving teaching skills, but more
      broadly as nurturing the growth of trainees into accomplished faculty--is
      critical to the existence of academic medical centers. Profound changes in
      academic medicine and health care delivery are making the traditional model of
      faculty development obsolete. That model is now inadequate and untenable in the
      face of shrinking government support, changes in the sophistication, costs, and
      funding of biomedical research, changes in the reimbursement systems for
      hospitals and physicians, a general loss of respect for the medical and
      scientific professions, and radical changes in the structure of the health care
      delivery system. The changes have implications for the type of faculty
      development needed for this new environment, and a new model is outlined.

PMID- 7826436
TI  - Sexual orientation and nondiscrimination policies.

PMID- 7826437
TI  - How an academic health center and a community health center found common ground.
AB  - Despite their divergent missions, academic health centers (AHCs) and community
      health centers (CHCs) are natural partners. This is becoming more obvious as
      national attention is focused on greatly increasing the number of primary care
      providers. AHCs are responding to this pressure and now need more sites to train
      primary care physicians, and CHCs need more primary care physicians (the AHCs'
      graduates) as staff. Thus these two types of institutions have a common interest.
      Other major themes of health care reform are also likely to drive AHCs and CHCs
      together, such as providing access to the uninsured, placing more emphasis on
      prevention and public health, and coordinating care in managed care systems to
      improve outcomes and control costs. Yet partnerships between these two kinds of
      institutions are still rare. This article describes a successful joint program
      begun in 1991 between the Lincoln Heights Health Center, which serves a poor,
      predominantly black community, and the University of Cincinnati Medical Center.
      All the program's activities are monitored by a policy committee made up of
      representatives from both institutions. For the first five years, the main
      hospital of the medical center is supporting the relationship with a $350,000
      grant. Both parties retain their independent governance, yet collaborate closely
      and feel the relationship yields high value to each party and the community. For
      example, medical education in out-of-hospital settings has increased greatly, as
      have referrals to the AHC. The CHC has been able to recruit and retain high
      quality physicians; its balance sheet has been favorably affected also.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7826438
TI  - Who will teach? A fundamental challenge to medical education.
AB  - The level of expertise possessed by medical school faculty members is
      unprecedented. Unfortunately, faculty members' broad understanding of their
      domains has atrophied as the specialization they need to compete successfully in
      the clinical and research arenas has increased. Medical students are novices,
      needing teachers who possess broad knowledge and experience, who can integrate
      the specific areas of a subject with overarching themes, and who can teach at the
      students' level. Clinical subspecialists and researchers on faculties often are
      ill-equipped to teach medical students. Likewise, busy clinical preceptors may no
      longer have the latest understanding of pathophysiology. The usual solution of
      bringing a series of basic science and clinical faculty members to classrooms and
      seminar rooms often results in disjointed coverage of material. Expanding the
      values of the university to once again include the scholarship of integration and
      teaching would provide the best type of faculty.

PMID- 7826439
TI  - Medical education in Italy: a hard journey.

PMID- 7826440
TI  - Informatics and medical libraries: changing needs and changing roles.
AB  - Medical librarians play a crucial role in the evolution of institutional
      information policy. As information professionals, they share many similarities
      with their medical informatics counterparts. Both groups emphasize information
      delivery to the point of decision making; both groups serve as curators of
      institutional knowledge bases. If the term "publication" encompasses the delivery
      of clinical information relevant to individuals or populations, both librarians
      and medical informaticians have an immediate interest in the nature of biomedical
      publishing, particularly in areas of intellectual ownership, confidentiality,
      distribution, and access. Both groups also have been early leaders in applying
      information technology to solve pressing knowledge-management problems, and both
      groups have a strong commitment to educating colleagues in the effective use of
      information. Although the challenges faced by librarians and medical
      informaticians are sometimes different, the evolution of information technology
      and new forms of biomedical communication suggest that there is now a greater
      convergence between the two disciplines.

PMID- 7826441
TI  - Ambulatory-care clerkship and students' interest in internal medicine.

PMID- 7826442
TI  - Building bridges between two worlds: the NIH's office of alternative medicine.

PMID- 7826443
TI  - Station gender bias in a multiple-station test of clinical skills.
AB  - PURPOSE: To apply differential item functioning (DIF) procedures to investigate
      station gender bias in multiple-station tests of clinical skills, and to compare
      these results with those obtained by comparing the station-score distributions of
      men and women examinees. METHOD: The data were from 23 stations used in the
      selection of seven successive cohorts (1987-1993) of candidates to the Ontario
      Pre-Internship Program for graduates of foreign medical schools. The stations had
      been used on at least three occasions, with a minimum sample of about 210
      candidates per station. Each station's score was expressed as both a binary score
      and a continuous score, and DIF was assessed using the Mantel-Haenszel procedure
      with the binary scores and analysis of covariance with the continuous scores. For
      each station, DIF effect sizes were calculated and compared with the gender-group
      mean differences. RESULTS: Using the binary scores, significant DIF was observed
      for three stations; using the continuous scores, significant DIF was observed for
      five stations. Significant gender differences were observed in the scores of nine
      stations. In eight, these differences favored women. Overall, in more stations
      the direction of DIF favored the men, while the women demonstrated higher levels
      of ability. CONCLUSION: The results suggest the importance of using a DIF
      approach for controlling the "ability factor" in studies of this kind: although
      significant gender differences were observed in the continuous score
      distributions of nine stations, generally these differences were not indicative
      of station gender bias.

PMID- 7826444
TI  - Development of a measure of medical faculty attitudes toward clinical evaluation
      of students.
AB  - PURPOSE: This research involved the development, and in particular the evaluation
      of the reliability, of scales to measure medical faculty attitudes toward
      clinical evaluation (ACE) of medical students. The intent was to create measures
      that yield reliable data and have practical utility in medical education research
      and faculty development. METHOD: A systematic, eight-step scale development
      protocol was used to create the instrument. In early 1993 factor analysis was
      used on data from 217 clinical faculty at four medical schools to refine the
      measures. Internal consistency and test-retest reliability analyses were
      performed. Analyses were also done to determine whether the attitude scores were
      influenced by such faculty demographic attributes as employing medical school,
      gender, age, tenure track status, academic rank, or academic department. RESULTS:
      An initial pool of 52 items was reduced to 30 items based on iterative
      reliability studies. Factor analysis on the 30 items yielded two scales: (1)
      Quality of Evaluation Procedures, 12 items, alpha = .81; and (2) Content of
      Departmental Evaluations, eight items, alpha = .85. Test-retest reliabilities (12
      weeks) for the scales were .67 and .74, respectively. Faculty demographics did
      not influence attitudes about the quality of evaluation procedures. However,
      family physicians showed a slightly more positive attitude toward the content of
      departmental evaluations than did physicians in five other medical specialties.
      CONCLUSION: The goal of developing reliable measures of faculty attitudes toward
      clinical evaluation of medical students has been achieved. With baseline
      reliabilities established, future research should assess the validity and utility
      of the scales, especially in the context of clinical practice examinations.

PMID- 7826445
TI  - A standardized-patient assessment of a continuing medical education program to
      improve physicians' cancer-control clinical skills.
AB  - BACKGROUND: Although continuing medical education (CME) has long been used to
      inform physicians and teach specific skills, its efficacy in many areas is not
      well established. This randomized controlled trial assessed the effects of
      differing educational techniques on the cancer-control skills of 57 physicians.
      METHOD: The CME program was part of the Cancer Prevention in Community Practice
      Project in Hanover, New Hampshire, and was implemented in 1988. The program used
      several methods in its presentation, including interactive small-group
      discussion, role playing, videotaped clinical encounters, lecture presentations,
      and trigger tapes. Measurements included cross-sectional observations made by
      unannounced standardized patients (SPs) who, one year after the CME program,
      assessed 25 physicians who had participated in the program and 32 physicians who
      had not. To measure consistency in the SPs' performances and accuracy in
      assessing the physicians' performances, most interactions were audiotaped using a
      hidden microphone. Pearson chi-square, Fisher exact two-tailed test, and kappa
      coefficients were used for analysis. RESULTS: Significantly higher ratings were
      found for the CME physicians in two areas: breast cancer risk-factor
      determination (determined maternal history: 80% versus 52%, p = .03; determined
      age at first period: 16% versus 0%, p = .02), and smoking cessation counseling
      (providing written material: 32% versus 9%, p = .03). The CME physicians were
      rated higher on all 19 study variables in the target areas of early detection of
      breast cancer and smoking cessation. The results show that the physicians'
      performance were better in those areas where the CME program had used performance
      based learning, such as role playing or viewing and discussing a videotaped role
      play encounter. CONCLUSION: The educational techniques that rehearsed or
      portrayed clinical applications seem to have increased the physicians'
      performances of cancer-control clinical activities. The standardized-patient
      instrument seems to be particularly useful in evaluating interventions that
      address specific skills training.

PMID- 7826446
TI  - Traditional predictors of academic performance in a medical school's independent
      study program.
AB  - PURPOSE: To provide predictive information as an initial screening device for
      admission decisions, generalizable to the population of students opting for the
      Independent Study Program (ISP) at The Ohio State University College of Medicine.
      METHOD: A stepwise multiple-regression technique was used to generate predictor
      criterion relationships. A priority code was developed as an applicant screening
      device. The code is a numeric value based on a combination of applicant grade
      point average (GPA) and Medical College Admission Test (MCAT) scores that
      provides a prediction of first-year performance in medical school. The study
      sample consisted of the 596 first-year students in the ISP track from 1980
      through 1989. The measure of their academic performances was the average score on
      three National Board of Medical Examiners (NBME) subject ("shelf") examinations
      in the basic sciences (anatomy, physiology, and biochemistry). RESULTS: The
      largest multiple correlations were found between averaged scores on the NBME
      subject examinations and undergraduate GPAs (R = 34.20; F = 16.79; p = .0001) and
      scores on the MCAT Biology Knowledge (R = 13.24; F = 47.64; p = .0001), MCAT
      Chemistry Knowledge (R = 7.86; F = 17.39; p = .0001), and MCAT Skills Analysis:
      Quantitative (R = 1.39; F = 3.93; p = .0479). CONCLUSION: The predictive value of
      traditional predictors of preclinical academic performance was established for
      the nontraditional program at The Ohio State University College of Medicine.
      Admission officers at other schools may find the priority code helpful as a
      sorting tool. It may further serve as an "early warning" system for students with
      marginal academic preparation.

PMID- 7826447
TI  - Housestaff's knowledge of their patients' social histories.
AB  - PURPOSE: To assess the extent to which house officers know the social histories
      of their hospital patients, and to examine the factors that influence social
      history knowledge. METHOD: In October-November 1992, all 31 internal medicine
      housestaff rotating on the hospital inpatient services at the University of
      Kentucky A. B. Chandler Medical Center completed questionnaires regarding the
      social histories of up to three of their patients. Responses were analyzed using
      simultaneous multiple linear regression analysis. RESULTS: Standard questions
      about social history were answered correctly only 29% of the time (two of seven
      items). The overall knowledge of patients' social histories was significantly
      less for supervising residents than for interns (p = .03) and, independently, for
      housestaff with greater patient loads (p = .04). Knowledge of a patient's social
      history was not related to the particular inpatient service, time the patient was
      admitted, or other characteristics of the patients or residents. CONCLUSION: The
      internal medicine residents' knowledge of their hospital patients' social
      histories was limited, particularly when the residents had relatively heavy
      patient loads or supervisory roles in patient care. The data suggest that
      patients' social histories may have been underemphasized during the residents'
      training.

PMID- 7826448
TI  - Effect of experience on medical students' attitudes toward animal laboratories in
      pharmacology education.
AB  - BACKGROUND: Medical students' attitudes toward the use of animal laboratories in
      pharmacology courses may form a useful source of evaluative information about the
      laboratories' educational effectiveness. METHOD: In 1992-93, 144 second-year
      students at the Indiana University School of Medicine were surveyed--before and
      after completing four hands-on laboratories using dogs--for their assessments of
      educational and moral aspects of animal laboratories. Statistical analysis
      involved chi-square and Student's t test. RESULTS: Of the 144 students in the
      course, 143 responded to the first survey and 86 responded to the second. From
      before to after the lab experiences, the percentage of students who agreed that
      the labs would reinforce/had reinforced the lecture material increased from 38%
      to 69%. In both surveys, 10% of the students objected to the use of any animals
      in labs, and 24% (before) and 21% (after) objected to the use of dogs. Whereas
      the percentage agreeing that the labs involved a morally wrong use of animals
      rose from 11% to 22%, the percentage disagreeing with that notion rose from 53%
      to 61%. Between 50% and 60% of the students in both surveys opposed doing the
      labs by computer simulation or videotaped demonstration. CONCLUSION: Most
      students indicated that the laboratory experiences enhanced their understanding
      of the actions of drugs, were preferable to alternatives that did not use
      animals, and did not involve an immoral use of animals. On the other hand, the
      results suggest that the number of students who have negative feelings about the
      use of animals in laboratories, though small, tends to be larger than the number
      who express these feelings to faculty.

PMID- 7826449
TI  - Changing career patterns of deans of medicine, 1940-1992.
AB  - This study examined the occupational experiences of deans of medicine during five
      decades, 1940-1992, to explore whether changes in their prior career paths could
      explain the increasing turnover of deans that occurred during this period. The
      results indicate that deans are now more likely to have had previous
      administrative experience, as either chairs or lower-level administrators, than
      they were in earlier decades; in most cases, this administrative experience has
      occurred in the same institutions in which they were appointed to the deanship
      ("inside hires"). However, the greater number of deans with prior administrative
      experience cannot explain the increasing turnover of deans because administrative
      experience was associated with longer tenures. The kinds of positions the deans
      took upon leaving office did not change during the study period, particularly
      among those who had short tenures of four years or less. During the five decades,
      inside hires leaving during their first five years in office most often moved
      into faculty, chair, or lower-level administrative positions. Outside hires
      leaving during their first five years most often went on to higher-level
      administrative positions. The study results do not support the hypothesis that
      the shorter tenures of deans in recent decades are related to their previous
      professional experiences or to increasing opportunities for deans to move to
      better positions. In conclusion, the authors emphasize that organizational and
      environmental factors rather than deans' individual characteristics must have
      played the dominant role in the increasing turnover of deans of medicine in
      recent years.

PMID- 7826450
TI  - Health system reform and the generalist physician.
AB  - The quality of primary care services is central to reforming the health care
      system of the United States. The well-trained generalist is essential in a
      delivery system that emphasizes high-quality, cost-effective care. Several
      analyses estimate that within a few years the United States will have 100,000
      150,000 too many specialists, and some estimates show a shortage of perhaps
      35,000 generalists. Residents and residency programs in nongeneralist areas
      continue to increase, and two-thirds of graduates enter careers as specialists.
      Academic medical centers must assume major responsibility for changing their
      programs to produce the types of practitioners that U.S. society needs. Among the
      changes recommended or directed by advisory bodies and professional organizations
      are establishing a workforce commission to set long-term goals, limiting the
      number of first-year residency positions and allocating them to generalist and
      nongeneralist specialties, establishing a national payment system to support
      residency training, setting up transition payments to teaching hospitals that
      reduce their number of residency positions, and initiatives to graduate more
      minority and generalist physicians, improve geographic distribution, and expand
      the capacity for primary-care teaching.

PMID- 7826451
TI  - Continuous quality improvement and the education of the generalist physician.
AB  - The new health care environment--centered on patients, focused on health, and
      managed by generalists--requires new competencies for the generalist physician.
      Among these are knowledge and skills for the continuous improvement of health
      care. In many areas, generalist physicians already use quality improvement
      methods and principles to improve the health and health care of their
      communities. Efforts to teach medical students and residents to improve quality
      continuously in health care are beginning. Early lessons are: (1) quality
      improvement is most effectively learned in the context of real work; (2) initial
      emphasis must be on the basics; (3) the focus is on the needs of those we serve;
      (4) interdisciplinary skills are essential and best learned during clinical
      training; and (5) the best learning environment for future generalist physicians,
      one which results in optimism about the future and the ability to make things
      better, is an environment that is continuously improving.

PMID- 7826452
TI  - A quarter-century of experience with career change education: an option for
      turning specialists into generalists.
AB  - The Physician Refresher program, now 25 years old, at the Medical College of
      Pennsylvania offers training to clinically inactive physicians. The authors
      examined the characteristics of program participants to determine whether
      specialists who took the program to prepare for a change to a primary care career
      made the intended change. Application data from all registrants between 1982 and
      1993 were compared with data on previously reported groups from 1968-1975 and
      1976-1981. Specialist registrants' subsequent practice activities were documented
      from the AMA Medical Directory and the American Board of Medical Specialties
      Directory; a telephone survey elicited their reasons for making or not making the
      career change to primary care. During the last decade of the program women
      registrants constituted 36% of the total; international medical graduates (IMGs)
      43%; and clinically inactive physicians 38%. Specialists outnumbered those in
      primary care by two to one. Although 65% of specialists planned to switch to
      primary care, ultimately only 27% of the total did so; many, especially the IMGs,
      were serving the disadvantaged. Those who did not switch cited a variety of
      disincentives, including individual educational needs not met by a general
      refresher course. If the medical profession accepts the need to devise programs
      that "retool" specialists to provide primary care, those programs should be
      specifically designed to address the individual needs of the specialists
      involved. Concomitantly, the incentives to make the switch need to be enhanced.

PMID- 7826453
TI  - Primary care and non-primary care physicians: a longitudinal study of their
      similarities, differences, and correlates before, during, and after medical
      school.
AB  - PURPOSE--To investigate similarities and differences between physicians in
      primary care and non-primary care specialties on performance measures prior to,
      during, and after medical school, and on demographic characteristics,
      professional plans and preferences in medical school, professional activities,
      career satisfaction, perceived problems and research activities, and to predict
      primary--non-primary care career choices from information obtained in medical
      school. A questionnaire was mailed to 1,076 physicians who graduated from
      Jefferson Medical College between 1982 and 1986. Of those who responded (62%),
      232 were primary care and 406 were non-primary care physicians (29 physicians in
      mixed specialties were excluded). Data from the questionnaire concerning
      professional activities, satisfaction, problems, and research productivities were
      merged with the college's longitudinal study database. RESULTS--Comparisons of
      primary care--non-primary care physicians indicated no significant difference
      between them on performance measures before, during, and after medical school,
      with the exception that non-primary care physicians had higher scores on
      quantitative tests before medical school, and primary care physicians scored
      higher on a licensing examination of general clinical skills and patient
      management taken during residency training. Also, compared with non-primary care
      physicians, those in primary care were less likely to be employed full-time, were
      less likely to locate in metropolitan areas, had a lower rate of academic
      appointment, and had a higher rate of board certification. Other results showed
      differences between the groups in terms of age at entrance to medical school,
      proportion of women, estimates during medical school of anticipated income,
      career plans during medical school, satisfaction with career and income, and
      research and scientific activities. A logistic regression model could predict
      primary care--non-primary care status from specialty interest, professional plans
      and interests expressed in medical school.

PMID- 7826454
TI  - Generalism and the need for health professional educational reform.
AB  - Powerful forces are intensifying change in health care delivery: population-based
      thinking about health care, especially emphasis on prevention; the reemergence of
      the biopsychosocial mode of thinking in health care; the need to increase
      capacity for health services research; and the knowledge that reductions may be
      needed in the use of high-priced physicians, the number of acute-care hospital
      beds, and the duplication of expensive equipment. Academic health centers are
      being forced to adjust their educational offerings to these realities of the
      service sector. Yet, institutional obstacles stand in the way of needed education
      reform: fragmentation of the sense of community in health professions schools,
      turf-related forces that separate various health professions, inflexible
      institutional structures that prevent adequate responses to a changing
      environment, an increasingly acute shortage of money to support education, and
      the devalued status of teaching within our institutions. Universities must
      develop centers to determine regional and local workforce needs and subsequently
      establish regionally based educational networks of academic and community health
      centers. Further, academic centers must demonstrate a real commitment to
      multiprofessional, interdisciplinary team approaches to a patient-centered
      system. In parallel, the institution must create a student-centered value system.

PMID- 7826455
TI  - A generalist's place is (also) in the home.
AB  - Regardless of how many generalist physicians we eventually have, patients will
      not get the treatment they need if doctors continue to work without house calls.
      For decades, patients have been coaxed out of their sickbeds to report to
      emergency rooms during "off hours," and once in the emergency room they are part
      of high-tech, test-driven health care. Only a return of the house call by the
      personal physician can reliably forestall this protocol-driven excess. There are
      obstacles aplenty to reviving the house call: few teachers survive who can teach
      this art; doctors now consider the house call burdensome work; present payment
      does not cover the costs; and doctors won't be safe on the streets at night. Some
      bureaucratic changes will be needed, of course, but most changes have to do with
      skills and attitudes. Care in the home is appropriate for many acute illnesses
      and chronic conditions. Patients need it, and doctors should provide it.

PMID- 7826456
TI  - Health care reform and medical education: forces toward generalism.
AB  - The transformation of U.S. health care is driven by underlying principles. The
      tensions between what exists now and what will emerge over the next 15 years
      pervade health care delivery and financing, the doctor-patient relationship, the
      provider-payer relationship, and the atmosphere within educational institutions
      for the health professions. The institutions that early on develop the capacity
      to forge and sustain strategic partnerships will be well positioned to take
      advantage of the opportunities of a rapidly changing system, but those that do
      not will risk being isolated without the diversity of resources needed to make
      meaningful contributions to health care. The tensions also drive major changes in
      the way health professionals are educated, trained, and deployed. Health care
      reforms will dramatically change the culture of the medical school in areas of
      patient care, research, and education programs. These institutions face external
      pressures to change and internal barriers to change, not the least of which are
      the lack of sustained leadership and collective vision. Academic medical centers
      must take active steps now to assess their strengths and weaknesses objectively,
      look realistically at options, and construct new, mutually beneficial
      partnerships that will be the keys to success.

PMID- 7826458
TI  - Academic health centers and HMOs: a systems perspective on collaboration in
      training generalists physicians and advancing mutual interests.
AB  - Academic health centers (AHCs) and health maintenance organizations (HMOs) often
      hold each other at arm's length because of fundamental organizational
      differences. AHCs view HMOs as too intrusive in the clinical management of
      patients and too concerned with the financial bottom line. HMOs view AHCs as
      organizationally fragmented and expensive in providing health care services. AHCs
      must expand their primary care networks and reassess their mission and public
      accountability in training a more balanced physician workforce. HMOs are growing
      rapidly and need well-trained generalist physicians to support that growth. This
      paper uses an organizational systems model in examining AHCs and HMOs to identify
      common needs, mutual interests, areas for potential collaboration, and bridging
      strategies. These include health care systems development, professional
      education, information management systems, and health services research. As the
      financing and delivery of health care continue to change and to become more
      integrated, both organizations have much to gain from collaboration.

PMID- 7826459
TI  - A model for improving generalist physician output: the osteopathic experience.
AB  - Osteopathic medicine is identified closely with primary care. Approximately one
      half of all doctors of osteopathy (DOs) are family practitioners. The educational
      model responsible for producing such a high percentage of generalist physicians
      should be better understood for its achievements. Colleges of osteopathic
      medicine are unique in sharing a common mission of producing primary care
      physicians, and their methodologies reflect a similarly shared educational
      emphasis. Compared to allopathic medical schools, colleges of osteopathic
      medicine are the highest producers of generalist physicians because of several
      common features. This article evaluates colleges of osteopathic medicine by
      profiling each institution according to characteristics that have a potential
      impact on the output of generalist physicians: (1) institutional ownership; (2)
      age; (3) class size; (4) leadership; (5) educational focus; (6) whole-time as
      opposed to adjunct clinical faculty; (7) clinical educational settings; (8)
      clinical training sites; and (9) reliance on MD rather than DO clinical faculty.
      Comparisons between colleges of osteopathic medicine according to these
      characteristics yield mixed results but also highlight many differences from
      allopathic educational models. Factors separating the highest from lowest
      producers of generalist physicians vary at colleges of osteopathic medicine, and
      other characteristics or circumstances beyond their control may affect the number
      of graduates pursuing careers in primary care.

PMID- 7826460
TI  - A longitudinal primary care program in an urban public medical school: three
      years of experience.
AB  - The experience of the University of Illinois at Chicago's College of Medicine
      with implementing a pilot generalist program focuses on institutionalization and
      management. Various features of the program make it an interesting case study: It
      is inter-disciplinary, comprising pediatricians, general internists, and family
      practitioners; students join the program in the autumn of their first year; and
      it is changing from a voluntary to a required, institutionally ingrained course
      of study. The difficulties and procedures encountered in making room for an
      interdisciplinary primary care program in a traditional medical school curriculum
      are discussed.

PMID- 7826457
TI  - Challenges to generalism: views from the delivery system.
AB  - The declining interest in primary care among U.S. medical students is an ominous
      trend for the national health system. The medical school environment, the
      powerful financial incentives promoting specialism, and the practice environment
      itself have contributed to the decline of generalism. During a day-long meeting
      sponsored by the Robert Wood Johnson Foundation, representatives of group
      practices, HMOs, community health centers, and military medicine noted the
      universal shortage of primary care physicians, the fact that medical education
      does not prepare physicians for the realities of practice, the concern that
      "burnout" is a significant problem for retention and physician satisfaction, and
      the problem that the optimal design of primary care practice is not yet known. To
      reverse these trends, concerted action must take place within academic medicine,
      by public policy makers, and by the delivery system itself.

PMID- 7826461
TI  - Defining a generalist education: an idea whose time is still coming.
AB  - Generalist education is different from the traditional medical curriculum as it
      has developed over the past 40 years. For example, in their training doctors must
      develop the appropriate skills, knowledge, and attitudes to understand patients'
      specific expectations, address wellness rather than illness only, be familiar
      with concepts of clinical epidemiology, concentrate on interpersonal
      communication, and strive to control costs. The University of Illinois College of
      Medicine at Rockford was established to provide community-based medical
      education. Beginning in their second year, all Rockford students have extensive
      clinical training in one of three community health centers operated by the
      Department of Family and Community Medicine. Several kinds of evaluation have
      been conducted to assess the reaction to and impact of this clinical training on
      the students and faculty, and follow-up studies have tracked the students after
      graduation. The Rockford experience has shown that the entire curriculum must
      give uncompromising support for generalist education, all primary care faculty
      must have a common knowledge base in the theory and practice of generalist
      medicine, and the shift to generalist education will require shifts in attitude
      and behavior throughout the academic medicine community at the institution.

PMID- 7826462
TI  - Generalism in medical education: the next steps.
AB  - The Association of American Medical Colleges accepted in full the strategies
      recommended by its Generalist Task Force in 1992, in particular the central goal
      that a majority of graduating medical students be committed to careers in
      generalist specialties and that medical schools make appropriate efforts to reach
      this goal as quickly as possible. Both generalists and specialists need a revised
      education. For example, they will have to master intellectually challenging
      analytic sciences fundamental to general practice, such as clinical epidemiology,
      decision analysis, health care economics, and medical informatics. Also, they
      must be educated in ambulatory care settings, which are most like generalist
      medical practice. Also, the medical faculty must contain large numbers of
      generalists, who will serve on important institutional committees and be involved
      in health services research and decision analysis. To educate generalist
      physicians, academic medicine must tackle many challenges effectively. It will,
      because medical education has a fundamental responsibility to produce a physician
      workforce that meets the needs of the American people.

PMID- 7826463
TI  - The interdisciplinary generalist curriculum project: a national medical school
      demonstration project.
AB  - The United States is facing the challenge of producing more generalists for the
      physician workforce. The Primary Care Organizations' Consortium (PCOC) has
      responded by focusing on how medical education can be modified to enhance and
      support medical students' interest in and commitment to generalism early in their
      training. Evolving from PCOC's developmental work, the five-year
      Interdisciplinary Generalist Curriculum (IGC) Project was developed to encourage
      the nation's schools of medicine and colleges of osteopathic medicine to
      implement interdisciplinary generalist curricula in the preclinical years. Funded
      by the Division of Medicine in the Bureau of Health Professions of the Health
      Resources and Services Administration (HRSA), the IGC Project has successfully
      developed and implemented a nationally competitive medical school demonstration
      project. Thirty-three schools submitted proposals for an IGC Project award; nine
      were selected for site visits, from which five were chosen to receive three-year
      awards. Rigorous attention to creating and maintaining an interdisciplinary focus
      has characterized the first phase of the IGC Project. Shared leadership among the
      Executive Committee's project director and two project codirectors and parity in
      representation among the three disciplines of family medicine, internal medicine,
      and pediatrics on the Advisory Committee have formed a critical foundation for
      interdisciplinary functioning within the project. Growing national interest in
      generalist training and other funding initiatives have contributed to acceptance
      of the IGC Project. The high level of interest in the IGC Project and the
      successful interdisciplinary collaboration during the first phase would indicate
      that the interdisciplinary process can be replicated to move the nation's medical
      education institutions toward the production of needed generalist physicians.

PMID- 7826464
TI  - Medical student initiatives to promote the education of generalist physicians.
AB  - Medical student organizations--including the American Medical Student Association
      (AMSA), the Association of American Medical Colleges's Organization of Student
      Representatives (AAMC-OSR), and the American Academy of Family Physicians'
      National Congress of Student Members (AAFP-NCSM)--are responding to the increased
      need for generalist physicians. Through a variety of initiatives drawing on each
      organization's unique strengths and capabilities, students are developing
      curricular and extracurricular initiatives to increase trainees' exposure to and
      knowledge about generalist medicine. These projects indicate that future
      physicians are interested in learning about generalist careers and in working
      with generalist mentors early in their medical training. Students are addressing
      these needs through community-based experiences, student interest groups,
      legislative activity, curricular reform, and research in generalist medicine.

PMID- 7826465
TI  - Overcoming barriers to generalism in medicine: the residents' perspective.
AB  - At a 1993 conference sponsored by the U.S. Bureau of Health Professions, a group
      of residents in several disciplines discussed barriers to generalism in medicine
      and ways to overcome them. In medical school, the barriers have to do with the
      lack of strong generalist mentors and lack of appropriate training in ambulatory
      generalist practice. In residency programs, the system does not support
      continuity of care and contains too few generalists as preceptors in clinical
      settings. The ambulatory clinic's inefficiency reinforces residents' frustrations
      and disillusionment with primary care practice. Further, the culture of medicine
      denigrates generalism and gives prestige and respect to subspecialists. In
      academic medicine, the dichotomy between scientist-physicians and clinician
      physicians is a barrier. The public has adopted the perception promulgated by the
      medical leadership that generalists are less skilled and have less to offer than
      subspecialists. The residents offered recommendations for medical schools
      (changes in faculty and administration, curriculum, and financial support), for
      residency programs (changes in curriculum and structure), for the culture of
      medicine, and for public awareness. To increase the role of the generalist
      physicians, academic medicine institutions must pursue systematic, broad-based
      approaches to overcome barriers to generalist education and practice.

PMID- 7826466
TI  - Meeting the faculty development needs of generalist physicians in academia.
AB  - Development of the academic environments of generalist faculty members is
      essential if they are to develop the skills to become leaders in medical
      education and primary care research and effective role models for their students.
      We conducted a needs assessment that included two-thirds of the generalist
      faculty members in family medicine, internal medicine, and pediatrics at the
      University of Texas Medical Branch, Galveston, Texas. The assessment was based on
      open-ended discussions in small focus groups and on responses to an informal
      checklist of 24 potential faculty development goals. The participants identified
      three global needs requiring significant change: (1) better understanding of and
      rewards for their academic activities, (2) better networking with each other and
      with nongeneralists, and (3) more control over their time and responsibilities.
      Individual needs for academic development were diverse but emphasized teaching
      and career-building skills. Meeting the individual needs of generalist
      academicians depends on addressing environmental obstacles to their academic
      development. We recommend building project-oriented teams that collectively
      develop skills in strategic planning and project management, political
      negotiation and public relations, and creative use of institutional support
      systems. Individual faculty development can then be linked to the development of
      high-priority group projects that stimulate learning and allow opportunities to
      practice new skills.

PMID- 7826467
TI  - Pyrroloquinolinone methylderivatives, furocoumarin analogues: interaction with
      biomolecules and computer-aided studies.
AB  - Pyrroloquinolinones, furocoumarin analogues, contain a divinilbenzene moiety,
      suggesting possible photoreactivity. Quantum mechanics calculations indicate that
      the pyrrole-side double bond exhibits strong photoreactivity, while the pyridone
      side double bond is only poorly photoreactive. Intercalation models obtained by
      molecular mechanics calculations suggest that, in the cis-syn intercalation
      arrangement, the pyridone-side double bond is well aligned with the nearby
      thymine, supporting possible C4-cycloaddition with the 5,6 double bond of
      thymine, while the pyrrole-side double bond assumes an unfavourable position for
      photobinding. These data suggest that photoreaction between the pyridone-side and
      thymine double bonds may takes place, although with very low yield. Experimental
      evidence concerning DNA-photobinding exhibited by 2,6-dimethyl-9-methoxy-4H
      pyrroloquinolinone (Compound I) confirms theoretical predictions. The formation
      of C4-cycloadducts between the pyridone side double bond and thymine also takes
      place with very low yield. Compound I shows marked BSA photobinding, suggesting
      that pyrroloquinolinones may photoreact with proteins. The three
      pyrroloquinolinones examined show high yields of singlet oxygen generation,
      suggesting that photobiological effects may be obtained through this photodynamic
      pathway, rather than through DNA photobinding.

PMID- 7826468
TI  - Non-steroidal antiinflammatory agents. Synthesis and enzyme inhibition of 2-[4
      (heteroarylmethyl)phenyl] propanoic acids and analogues.
AB  - Some 2-[4-(heteroarylmethyl)phenyl]propanoic acids and phenylacetic and benzoic
      analogues has been synthesized. All above acids were tested for their inhibitory
      activity on lipoxygenase and cyclooxygenase, in comparison with NDGA and
      tolmetin. 2-[4-(Thien-2-ylmethyl)phenyl]propanoic acid 2, strictly related with
      suprofen, was found the most interesting compound, giving rise to a 79%
      inhibition of the cyclooxygenase activity at 10(-4) M concentration.

PMID- 7826469
TI  - New 1-[quinolyl(4)]-1,2,3-triazoles: synthesis and evaluation of antiinflammatory
      and analgesic properties. II.
AB  - Several 1-[quinolyl(4)]-1,2,3-triazoles were synthesized by 1,3-dipolar
      cycloaddition of 4-azidoquinolines with activated methylene compounds. The
      synthesized compounds, tested for antiinflammatory and analgesic activities,
      resulted moderately active as antiinflammatories, but with a very interesting
      analgesic activity, sometimes higher than that of indomethacin, used as reference
      drug. Some of the triazole derivatives were evaluated also as antimicrobial, but
      none of them exhibited activity.

PMID- 7826470
TI  - 3-Cyclopentyl-1-adamantanamines and adamantanemethanamines. Antiviral activity
      evaluation and convulsions studies.
AB  - The synthesis of 3-cyclopentyl-1-adamantanamines and adamantanemethanamines and
      some of their thioureas is described. The antiviral activity examination of these
      compounds indicated that some of them inhibited Respiratory Syncytial Virus (RSV)
      infection at concentrations that were slightly (up to 5-fold) lower than the
      cytotoxic concentration. Behavioral and convulsions studies of the above
      mentioned amines, in mice, did not show any dopaminomimetic activity and argue in
      favor of the existence of a glutamatergic component in the action of these
      derivatives.

PMID- 7826471
TI  - Synthesis and antitumor activity evaluation of 1-[(arylidene)amino]adamantanes.
AB  - Several 1-[(arylidene)amino]adamantanes were synthesized and evaluated in vitro
      as antitumor agents against 60 human tumor cell lines. Some of these derivatives
      showed specificity for human leukemia cell lines and 1-[(2
      bromobenzylidene)amino]adamantane (2) (NSC 631076-L), the most active compound,
      was selected by the Biological Evaluation Committee (BEC), for in vivo testing.

PMID- 7826472
TI  - Cyclic amidine analogues of taurine and homotaurine: synthesis and effects on rat
      skeletal muscle.
AB  - A series of amidinosulfonic acids IIIa-f, analogs of taurine and homotaurine, was
      synthesized by reacting 2-aminoethane or 3-aminopropane sulfonic acid with lactim
      ethers Ia-c and then cyclized to sultams IVa-c and Vd-f. The effects of some
      selected amidinosulfonic acids III on membrane ionic conductances of rat skeletal
      muscle are described.

PMID- 7826473
TI  - The effect of phenobarbital on the nonenzymatic glycation of hemoglobin.
AB  - The effect of phenobarbital (PB) on nonenzymatic glycation of hemoglobin in vivo
      and in vitro was studied. In epileptic patients on long-term therapy with PB, the
      yield of glycated hemoglobin fraction HbA1c was found to be significantly higher
      than in normal control. In samples of Hb exposed to glucose in vitro in the
      presence of PB, HbA1c was also found to be significantly higher than in those
      exposed to glucose in the absence of PB. Enhanced reactivity of beta-NH2 terminus
      of Hb with glucose, was partly explained by observing that its pKa was decreased
      in the presence of PB. It was shown that the effect of PB on pKa of beta-NH2
      terminus is one of the consequences of the Hb-PB interactions which were studied
      in this work by electrophoretic and NMR techniques.

PMID- 7826474
TI  - Analgesic and antiinflammatory activity screening of 6-acyl-3-piperidinomethyl
      2(3H)-benzoxazolone derivatives.
AB  - 6-Acetyl-2(3H)-benzoxazolone derivatives were reacted with appropriate piperidine
      derivatives and formaldehyde in methanol to give the corresponding 6-acyl-3
      piperidinomethyl-2(3H)-benzoxazolones. The obtained compounds were screened for
      their analgesic and antiinflammatory activities. Analgesic activity of these
      compounds was investigated by modified Koster test. Antiinflammatory activity was
      assayed by using carrageenan induced mouse paw edema test and arachidonic acid
      edema. The 15 compounds synthesized showed good analgesic activities; compounds
      1,3 and 6 moved to be active inhibitors of edema.

PMID- 7826475
TI  - Antigravitropic activity of 2-(2-arylamino-1,2-dioxoethyl) benzoic acid methyl
      esters.
AB  - Methylation of 1,3-dihydro-1-hydroxy-3-oxo-1-isobenzofurancarboxamides (A-I)
      yields 2-(2-arylamino-1,2-dioxoethyl)benzoic acid methylesters. The esters 1-7
      allowed the evaluation of the intrinsic activity of 2-(2-arylamino-1,2
      dioxoethyl)benzoic structure, to whom the antigravitropic effect of the
      carboxamides A-I may be probably assigned. The comparison of activities of
      methylesters 1-7 (B) and 8-14 (C) shows how conformational differences as those
      between the arylamino-1,2-dioxoethylic portion of B and the arylamino-2
      oxoethylic portion of C may deeply effect phytotropin interaction with the
      receptor site.

PMID- 7826476
TI  - New heterocyclic derivatives of benzimidazole with germicidal activity--XI-
      Experimental validation of OSAR prediction on antibacterial and antimycotic
      activity of benzimidazole derivatives.
AB  - In continuation of previous studies, Authors describe the synthesis of three new
      derivatives of 2-(5'-nitro-2'-furyl) benzimidazole, having hydroxy, methoxy or
      amino group at position 5. The new compounds, synthesized as suggested by a
      previous chemometric study, were tested in vitro against 5 Gram + and 4 Gram-
      strains and the mycete C. albicans. Two derivatives (R = OH, NH2) showed a good
      degree of antibacterial activity, especially the 5-hydroxy derivative, but they
      were practically inactive against the mycete; these results are in agreement with
      the prediction of chemometric study.

PMID- 7826477
TI  - Antibacterial activity of N-phenylmaleimides, N-phenylsuccinimides and related
      compounds. Structure-activity relationships.
AB  - The antibacterial activity of several phyllanthimide analogs were investigated by
      the Minimum Inhibitory Concentration Method (MIC) against E. coli and S. aureus.
      It was found that maleimides were approximately 30 times more active than
      succinimides indicating that the cyclic imido double bond is an important factor
      related to the activity. Electron-donor and electron-withdrawing substituents in
      the aromatic ring of N-phenylmaleimides decrease the activity of these compounds
      indicating the possibility of steric effects. The distance between the aromatic
      and the imido rings when separated by methylene groups does not affect the
      antibacterial activity.

PMID- 7826478
TI  - Synthesis of some 4-thiazoline and 4H-1,2,4-triazole derivatives of imidazo[1,2
      a]pyridine as possible anticonvulsants.
AB  - Several 2-[(2-methylimidazo[1,2-a]pyridine-3-yl)carbonyl]hydrazono- 3
      nonsubstituted/substituted-4-phenyl-4-thiazolines (3a-d, 3f-h) and 3-(2
      methylimidazo[1,2-a]pyridine-3-yl)-4-nonsubstituted/substitut ed-5- mercapto-4H
      1,2,4-triazoles (4a-f, 4i) were synthesized, characterized and evaluated for
      anticonvulsant activity. Only 3g showed significant activity against MES induced
      seizures.

PMID- 7826479
TI  - A skin hotline program.

PMID- 7826480
TI  - The foot: corns, calluses, ingrown nails and diabetic ulcers.

PMID- 7826481
TI  - Developing a successful interdisciplinary seating program.

PMID- 7826482
TI  - Case study: a system for stabilizing percutaneous tubes.
AB  - It is necessary to stabilize percutaneous tubes to prevent skin irritation and
      leakage. A stabilizing system was created using a drain tube attachment device
      and a urostomy pouching system. The system prevents tube movement and leakage,
      and provides a skin barrier. A case study is presented that illustrates the use
      of the system. The attachment and pouching system stabilized the tube and
      prevented leakage while being simple to use for patient and caregiver. The
      patient was able to ambulate and dress normally using the system upon discharge.

PMID- 7826483
TI  - Three methods of stool management for patients with diarrhea.

PMID- 7826484
TI  - Survival skills: a patient teaching model for diabetes mellitus.

PMID- 7826485
TI  - O/WM commentary: the perils of povidone-iodine use.

PMID- 7826486
TI  - Early noncognitive change in Alzheimer's disease and healthy aging.
AB  - Recent studies in Alzheimer's disease have focused on behavioral disturbances in
      the more advanced stages of the illness rather than behavioral and personality
      changes occurring early in the disease course. We present a new instrument, the
      Oregon Noncognitive Inventory for Dementia (ONID), that was developed
      specifically for patients in the early stages of dementia, to identify subtle
      behavioral alterations that may precede the more severe cognitive changes of
      Alzheimer's disease. Mildly demented Alzheimer's patients were compared with age
      matched healthy subjects on the ONID. Caregivers of these patients reported
      significantly more of the behaviors addressed by the ONID than did relatives of
      the healthy elderly. The results indicate that changes in behavior and
      personality can be reliably reported by family caregivers of patients with mild
      dementia. Future clinical applications of the ONID might include measuring change
      in drug trials, longitudinal studies of the progression of change, and
      differentiating Alzheimer's disease from other dementias based on a
      characteristics pattern of change.

PMID- 7826487
TI  - Clinical characteristics of chronic Creutzfeldt-Jakob disease.
AB  - Chronic Creutzfeldt-Jakob disease, presenting in later life, may be difficult to
      distinguish from other dementing illnesses. Patients with this disease may lack
      the characteristic myoclonus and electroencephalographic complexes. We report
      four patients with a slowly progressive dementia who were misdiagnosed during
      life and had a spongiform encephalopathy at autopsy. All four patients had early
      extrapyramidal rigidity, primitive reflexes, and other neurologic signs. The
      presence of these neurologic findings early in the course of a dementia suggests
      that clinicians should consider chronic Creutzfeldt-Jakob disease, evaluate the
      patient with electroencephalographic studies, and emphasize universal tissue
      precautions.

PMID- 7826488
TI  - Prevalence of personality disorders in two geropsychiatric inpatient units.
AB  - One hundred males from a Veterans Affairs geropsychiatric inpatient ward, and 100
      females from a geropsychiatric inpatient ward of a private hospital completed the
      Structured Interview for Disorders of Personality-Revised (SIDP-R). Chart reviews
      provided information including age, years of education, marital status, race, as
      well as Axis I and Axis II psychiatric diagnoses. Data from a young adult sample,
      drawn from an initial SIDP-R validation study, were used for comparison. Results
      indicate a 56.5% rate of personality disorders (PD) for older patients.
      Significantly more elderly men than elderly women were diagnosed with PD by
      psychiatric evaluation, and elderly men were also more likely to be diagnosed
      with paranoid, avoidant, and multiple PD using the SIDP-R. Psychiatrists gave far
      fewer Axis II diagnoses than were yielded by the SIDP-R, particularly with
      females. There were no significant differences in total PD rates between aged and
      young subjects, but older adults with PD were diagnosed less frequently with
      multiple PD. Older adults were also less likely to be diagnosed with the
      "Dramatic" cluster PD, and more likely to be diagnosed with the "Odd" cluster PD.
      The level of depression was related to both clinical and SIDP-R diagnoses.

PMID- 7826489
TI  - The Zung Self-rating Depression Scale: screening for depression among the Hong
      Kong Chinese elderly.
AB  - Two studies were conducted respectively to examine the reliability and validity
      of the standard Zung Self-rating Depression Scale (SDS), and a 10-item shorter
      version of the same test. In particular, the scale's usefulness as a screening
      instrument for depression among the Hong Kong Chinese elderly was investigated.
      In addition to the SDS, the Geriatric Depression Scale and the Chinese Hamilton
      Depression Scale were used to assess the convergent validity of the SDS. Data
      were collected from 113 nondepressed community-dwelling and 80 depressed elderly
      subjects. The findings showed that both the original and the shorter version of
      the SDS were highly reliable and valid. Both versions were appropriate for use as
      screening instruments for geriatric depression in Hong Kong. When compared with
      the original scale, the shorter version appeared to be slightly superior in its
      sensitivity and specificity in discriminating between the depressed and
      nondepressed subjects.

PMID- 7826490
TI  - Association of antidepressants and other medications with mortality in the
      residential-care elderly.
AB  - To explore the extent to which treatment of depression affects survival, we
      evaluated the association between use of antidepressant medications and death
      rates among the residents of a large residential-care facility for the elderly
      using a retrospective record-review study (N = 624). One year survival, among
      those taking antidepressants (10.9%), was 11.8% compared to 11.1% among the
      remainder of the population. A second study followed a group of 32 patients in
      the same institution who had participated in a therapeutic trial of nortriptyline
      treatment for major depression. Patients who experienced adverse medical events
      during treatment exhibited significantly increased mortality; among treatment
      completers, there was no significant relationship between mortality and
      therapeutic response. These findings suggest that the inability to tolerate
      treatment with an antidepressant can be considered a manifestation of physiologic
      frailty and increased vulnerability to mortality from disease. The previously
      reported decrease in survival among residential-care patients with major
      depression is not paralleled by a similar effect in those taking antidepressants.
      This may reflect selection factors with respect to the ability to tolerate
      antidepressants, rather an effect of treatment.

PMID- 7826491
TI  - Treatment of depression in advanced Alzheimer's disease using sertraline.
AB  - Effects of sertraline on the affect and food refusal of patients with advanced
      dementia of the Alzheimer type (DAT are reported. Out of 10 patients with
      depressed affect, sertraline improved affect in eight. Six of these patients were
      also refusing food, and sertraline diminished food refusal in five of them. A
      case report of a patient who had a dramatic improvement in response to sertraline
      treatment is presented.

PMID- 7826492
TI  - Seizures in Alzheimer's disease: clinicopathologic study.
AB  - New-onset epileptic seizures occur in patients with Alzheimer's disease (AD), but
      the nature and underlying reasons for these seizures are unclear. We identified
      new-onset, nonsymptomatic seizures in 77 (17%) of 446 patients with
      uncomplicated, definite AD on autopsy. Among these seizure patients, 69 had
      generalized tonic-clonic seizures, and 55 had less than three total seizures. The
      seizure patients had a younger age of dementia onset than did the remaining AD
      patients; however, at seizure onset, they averaged 6.8 years into their AD and
      had advanced dementia. When further compared to 77 AD controls, matched for age
      of onset and duration, the seizure patients did not differ on medical illnesses,
      amount of medications, and degree of focal neuropathology. We conclude that a few
      unprovoked generalized seizures frequently occur late in the course of AD, and
      that AD patients with a younger age of dementia onset are particularly
      susceptible to seizures.

PMID- 7826493
TI  - Changes in tardive dyskinesia symptoms in elderly patients treated with
      ganglioside GM1 or placebo.
AB  - The unique role of ganglioside GM1 in neuronal plasticity led two centers, New
      York University and McLean Hospital, to study the effect of GM1 or placebo in
      patients with tardive dyskinesia. Results from the NYU cohort have already been
      published. We now present data from the entire cohort, allowing us to evaluate
      the effects of GM1 in the elderly compared to young adults. Subjects with tardive
      dyskinesia were randomly assigned to single-blind placebo injections for 1 week,
      followed by 1 month of double-blind intramuscular placebo or GM1 100 mg. The
      final sample included 29 patients: 12 younger than 55 years of age and 17 older.
      There was no GM1-versus-placebo difference observed in either age group, or in
      the total group. However, whether on placebo or GM1, repeated measures analysis
      of variance (RANOVA) found a significant difference in response between Abnormal
      Involuntary Movement Scale scores, taken baseline and week 4, in the elderly
      compared to young adults. Scores for the young adults show initial improvement
      then deterioration back to baseline, and those for the elderly show continuing
      improvement during the 4-week trial. The importance of the placebo effect in the
      elderly and its meaning for studies of GM1 in tardive dyskinesia are discussed.

PMID- 7826494
TI  - Prevalence of depression in Alzheimer's disease and validity of Research
      Diagnostic Criteria.
AB  - This study was undertaken to estimate the point-prevalence of Research Diagnostic
      Criteria (RDC) depressive syndromes in Alzheimer's disease (AD) and to evaluate
      the validity of existing and potential alternative diagnostic criteria for major
      depression in the presence of probable AD. Twenty-six subjects with probable AD
      of mild to moderate severity and their caregivers were interviewed to estimate
      the prevalence of RDC depressive syndromes. For the evaluation of the validity of
      RDC for major depression, an additional 8 probable-AD subjects with suspected
      depression were added to the sample. Sensitivity, specificity, and correlation
      with diagnosis of RDC major depression were calculated for each diagnostic
      criterion, and existing major depressive criteria were compared to potential
      alternative criteria currently used for RDC minor depression. Of the subjects in
      our prevalence sample, 15.4% were found to have major depression; 23.1%, minor
      depression; and 11.5%, intermittent depression. In our validation sample, two
      criteria for major depression, self-reproach/guilt and thinking/concentration
      difficulty, were weakly associated with the final diagnosis of major depression
      because of poor sensitivity or specificity. In contrast, three possible
      alternative criteria were significantly associated with the diagnosis of major
      depression and showed high sensitivity and specificity. These included nonverbal
      manifestations of depression, irritability/complaining, and
      demandingness/dependency. We conclude that RDC depressive syndromes are common in
      probable AD of mild to moderate severity. In the presence of AD, the validity of
      some existing major depressive criteria may be limited in comparison to several
      potential alternative criteria because of relatively poor sensitivity and/or
      specificity.

PMID- 7826495
TI  - The factor structure of the Brief Psychiatric Rating Scale in Alzheimer's
      disease.
AB  - The factor structure of the Brief Psychiatric Rating Scale (BPRS) is well
      established with young psychiatric patients. A study by Overall and Beller
      showed, however, that its factor structure was different with geropsychiatric
      patients. Although the BPRS has been used in assessing the behavioral
      characteristics of patients with probable Alzheimer's disease (AD), its factor
      structure has not been established with these patients. The present study
      investigated the factor structure of the BPRS among patients with clinically
      diagnosed AD by (NINCDS/ADRDA) criteria. The scale had limited usefulness with
      outpatients with mild AD. The factor structure obtained was similar to that found
      with other patient groups, but a unique factor, including the items Tension and
      Uncooperativeness, probably reflects the behavioral and psychological agitation
      characteristic of some AD patients. We recommend caution be taken in generalizing
      data from younger psychiatric samples to older adult patients with dementia.

PMID- 7826496
TI  - Early detection of neuroleptic-induced parkinsonism in elderly patients with
      dementia.
AB  - The recently promulgated Health Care Finance Administration guidelines regarding
      the use of neuroleptic medications for nursing home residents do not offer
      criteria for the frequency or nature of the required assessments of neuroleptic
      induced parkinsonism (NIP). NIP has been poorly characterized in the elderly and
      empirical evidence on which to base guidelines for monitoring NIP is sparse. We
      examined the onset of NIP in 12 closely monitored, elderly psychiatric inpatients
      diagnosed with dementia being treated with perphenazine. Significant increases in
      the Simpson Extrapyramidal Side Effect Scale total score were detected by day 4
      of treatment with perphenazine at a mean dose of 8.0 mg. This increase was highly
      correlated with the final NIP severity. This is the first report to demonstrate
      that routine screening of elderly patients can detect NIP within days of the
      initiation of neuroleptic treatment. Early detection of NIP may allow for
      effective intervention to reduce the ultimate severity and associated morbidity
      of NIP.

PMID- 7826497
TI  - Fluoxetine-induced syndrome of inappropriate antidiuretic hormone secretion: a
      geriatric case report and a review of the literature.
AB  - In a frail, elderly, depressed patient, hyponatremia can present a difficult
      diagnostic and management challenge. We report the case of a severely depressed
      83-year-old woman presenting with severe hyponatremia, eventually attributed to a
      syndrome of inappropriate, antidiuretic hormone (SIADH) secretion induced by
      fluoxetine. This case is discussed in the context of the multiple potential
      causes of hyponatremia in an elderly depressed patient, with a focus on
      fluoxetine-induced SIADH, as reported in 9 other published cases.

PMID- 7826498
TI  - H5D12 monoclonal antibody identifies a 24-kD immunosuppressor factor produced by
      human chorio carcinoma cells.
AB  - PROBLEM: The purpose of this study was to identify and characterize embryo
      associated immunosuppressor factor (EASF) secreted by chorio carcinoma cells with
      the help of EASF-specific monoclonal antibody H5D12 (raised against EASF purified
      from embryo growth media of in vitro fertilized human ova). METHOD: Paraffin
      embedded slides of human chorio carcinoma as well as control cell lines were
      prepared, and immunohistochemistry was done by the avidin-biotin-peroxidase
      technique. EASF was affinity purified using H5D12-Sepharose 4B from culture media
      of cell lines and analyzed for immunosuppressive activity (by Concanavalin-A
      induced lymphocyte proliferation assay) and molecular weight identity (by
      metabolic-labelling studies with 35S-methionine followed by immunoprecipitation
      and SDS-PAGE). RESULTS: H5D12 showed intense immunostaining of BeWo chorio
      carcinoma cells. Biosynthetic labeling studies identifies this factor as a 24-kD
      molecule, and EASF bioassay indicates that this factor possesses
      immunosuppressive activity. No such immunosuppressive activity or similar
      molecules were identified when control cell lines were analyzed. CONCLUSIONS:
      Monoclonal antibody H5D12 recognizes a 24-kD factor with immunosuppressive
      activity that is secreted by chorio carcinoma cells, which suggests that this is
      a unique factor and may be one of the key regulators of reproductive functions.

PMID- 7826499
TI  - Macrophage inflammatory protein-1 alpha in term and preterm parturition: effect
      of microbial invasion of the amniotic cavity.
AB  - PROBLEM: This study was conducted to determine whether: (1) gestational age,
      parturition, and microbial invasion of the amniotic cavity (MIAC) are associated
      with changes in amniotic fluid concentrations of immunoreactive macrophage
      inflammatory protein-1 alpha; (2) amniotic fluid concentrations of macrophage
      inflammatory protein-1 alpha are correlated with the white blood cell count and
      the concentrations of interleukin-8 in amniotic fluid. METHOD: Amniotic fluid was
      retrieved by amniocentesis from 126 patients; 54 women with preterm labor and
      intact membranes (no MIAC-delivery at term, N = 21; no MIAC-preterm delivery, N =
      16; MIAC-preterm delivery, N = 17); 62 patients at term (no labor, N = 19; labor
      no MIAC, N = 20; labor-MIAC, N = 23); and 10 patients in the midtrimester of
      pregnancy. Amniotic fluid was cultured for aerobic, anaerobic and Mycoplasma
      species. Determinations of amniotic fluid macrophage inflammatory protein-1 alpha
      and interleukin-8 were performed with immunoassays validated for amniotic fluid
      (sensitivity: 14.2 pg/ml and 0.3 ng/ml, respectively). Kruskal-Wallis analysis of
      variance (ANOVA) for censored data, Mann-Whitney U test and Spearman's rank
      correlation were performed for analysis. RESULTS: 1) Amniotic fluid macrophage
      inflammatory protein-1 alpha was present in only 31.0% (9/29) of patients not in
      labor (midtrimester and term). 2) Patients with preterm labor and MIAC had higher
      amniotic fluid concentrations of macrophage inflammatory protein-1 alpha than
      those without MIAC (no MIAC-delivery at term: median 0.0 pg/ml, range 0.0-221.2;
      no MIAC-preterm delivery: median 37.4 pg/ml, range 0.0-494.6; MIAC-preterm
      delivery: median 7171.0 pg/ml, range 402.5-37994.0; P < 0.00001). 3) Among
      patients at term, MIAC was associated with higher concentrations of amniotic
      fluid macrophage inflammatory protein-1 alpha than patients without MIAC (no
      labor: median 0.0 pg/ml, range 0.0-25.6; labor-no MIAC: median 16.7 pg/ml, range
      0.0-161.6; labor-MIAC: median 103.8 pg/ml, range 0.0-4349.0, P < 0.001). 4) Among
      patients in preterm labor, a strong correlation was found between amniotic fluid
      concentrations of macrophage inflammatory protein-1 alpha and interleukin-8 (r =
      0.9, P < 0.00001) and between amniotic fluid macrophage inflammatory protein-1
      alpha concentrations and amniotic fluid white blood cell count (r = 0.6, P <
      0.0001). CONCLUSIONS: (1) Macrophage inflammatory protein-1 alpha is undetectable
      in most amniotic fluid samples from patients in the midtrimester of pregnancy and
      at term not in labor. (2) Microbial invasion of the amniotic cavity is associated
      with increased concentrations of immunoreactive amniotic fluid macrophage
      inflammatory protein-1 alpha in both term and preterm gestations. (3) Amniotic
      fluid macrophage inflammatory protein-1 alpha concentrations significantly
      correlate with interleukin-8 levels and white blood cell count in amniotic fluid.
      Our data strongly suggest a role for macrophage inflammatory protein-1 alpha in
      the mechanisms responsible for the recruitment of leukocytes into the amniotic
      cavity during the course of intrauterine infection.

PMID- 7826500
TI  - Monoclonal antibodies for reproductive health: Part I. Preventing sexual
      transmission of disease and pregnancy with topically applied antibodies.

PMID- 7826501
TI  - Introduction--The worldwide collaborative observational study and MULTI-analysis
      on allogeneic leukocyte immunotherapy for recurrent abortion.

PMID- 7826502
TI  - Worldwide collaborative observational study and meta-analysis on allogenic
      leukocyte immunotherapy for recurrent spontaneous abortion. Recurrent Miscarriage
      Immunotherapy Trialists Group.
AB  - PROBLEM: Recurrent spontaneous abortion (RSA) is a common complication of
      pregnancy for which there is no known cure. Therefore, effective treatment is
      needed. Published results from controlled clinical trials of allogeneic leukocyte
      immunization of women suffering from RSA have given conflicting results. To
      address this controversy, the international raw data of all patients who had been
      entered into clinical trials that included a control group were collected and
      analyzed. The primary question to be answered was whether alloimmune stimulation
      of the female partner improves the subsequent live birth rate. METHODS: Fifteen
      clinical centers were identified worldwide because they controlled appropriate
      raw data. Consequently, nine randomized trials (seven double-blinded) were
      evaluated independently by two separate data analysis teams to assure conclusions
      were robust. One team also compared randomized trials to the results of six
      nonrandomized cohort-controlled studies to test for bias in nonrandomized trials.
      Factors predicting successful live births among couples with RSA were evaluated
      by logistic regression. RESULTS: Although the two independent analyses made use
      of different definitions and utilized different statistical methods, the results
      of both were similar. The live births ratios (ratio of live births in treatment
      and control groups) with 95% confidence intervals (CI) were 1.16 (CI, 1.01-1.34,
      P = 0.031) and 1.21 (CI, 1.04-1.37, P = 0.024), respectively. The absolute
      differences in live birth rates between treatment and control groups were 8% and
      10% in respective analyses. Results in randomized and nonrandomized trials were
      surprisingly similar despite significant differences in composition of control
      and treatment groups. Live birth rates were lower with older female partners,
      more than five abortions, with a positive ANA or with positive anticardiolipin
      antibodies. Live birth rates were higher if the female partner had prior to
      treatment serum antibodies to paternal leukocytes or converted from negative to
      positive with immunization. Approximately 0.5% of controls and 2.1% of treated
      patients experience side effects for a 1.6% treatment related effect. There was
      no evidence of an increased risk of adverse effects on the fetus. CONCLUSIONS:
      Two independent analyses of worldwide data on allogeneic leukocyte immunization
      for treatment of RSA suggest that alloimmunization may be an effective treatment
      The treatment effect appears, however, to be small, and the data indicate that
      immunotherapy helps only 8% to 10% of affected couples. A current lack of
      diagnostic tests defining patients who most likely would benefit from
      immunotherapy, precludes the identification of a patient population that would
      benefit most from such treatment. The efficacy of treatment in such a subgroup
      could be expected to increase and could be of sufficient magnitude to allow the
      determination of more effective immunization protocols. This study does not
      exclude the possibility of a partial correction of a widely prevalent immunology
      defect by immunotherapy. The presence of such a defect would indicate a need for
      more effective therapy. The unexplained variation in pregnancy success rates of
      control groups among centers continues to present a statistical problem, limiting
      the statistical evaluation of retroactively obtained data.

PMID- 7826503
TI  - The effects of sera from women with spontaneous abortions on the in vitro
      development of early somite stage rat embryos.
AB  - PROBLEM: Spontaneous abortions occur in 40 to 50% of pregnancies, but the causes
      for some abortions, especially those that are recurrent (spontaneous), are still
      unknown. METHOD: Following previous studies that demonstrated embryotoxic effects
      of sera from women with spontaneous abortions in preimplantation mouse embryos,
      we cultured 10.5-day-old rat embryos in sera from women after spontaneous
      abortions to look for specific teratogenic effects. RESULTS: About 50% of the
      embryos cultured in sera from women after spontaneous abortions were malformed,
      as compared to 19.1 and 27.1% malformations in embryos cultured in sera from
      women after a normal delivery and during a normal second trimester of pregnancy,
      respectively. We divided the sera from women who had spontaneous abortions into
      high-risk, and low-risk sera. In the high-risk sera from one abortion, we found
      74.2% malformed embryos and in the high-risk group from two or more abortions
      this rate was 81.0%. This is compared to a rate of 17.1 and 10.3% in the low-risk
      sera, respectively. We have also found lower DNA and protein synthesis in the
      embryos cultured in high-risk sera compared to those cultured in low-risk and
      control sera. Transmission electron microscopy examination of yolk sacs cultured
      in high risk sera showed ultrastructural damage as represented by a lower number
      of microvilli and a higher number of inclusions in the entodermal cells when
      compared to controls. Amino acid chromatography of the serum and the
      concentrations of folic acid and zinc were similar in control and high-risk sera.
      CONCLUSION: It seems that the majority of sera from women with unexplained
      spontaneous abortions are teratogenic to rat embryos in culture. In about two
      thirds of these sera the teratogenic factor(s) seem to be present in the IgG
      fraction.

PMID- 7826504
TI  - Association between familial autoimmune diseases and recurrent spontaneous
      abortions.
AB  - PROBLEM: To examine the aggregation of autoimmune disease in the families of
      women experiencing recurrent spontaneous abortions. METHOD: The 95 participants
      in this case-control study were recruited from Magee Womens Hospital, Pittsburgh,
      Pennsylvania from June 1988 to May 1991. The women having recurrent spontaneous
      abortions (N = 45) reported at least three early fetal losses, and the controls
      (N = 50) reported a minimum of three pregnancies with at least two live births
      and no more than one induced or involuntary pregnancy loss. Data from the
      participants and from their first-degree and second-degree relatives were
      obtained by questionnaire and verified by a repeated interview, if necessary.
      RESULTS: The prevalence of arthritis, thyroid disease, and diabetes mellitus was
      increased among the relatives of women having recurrent spontaneous abortions
      compared to normally fertile couples. Several autoimmune diseases occurred
      concurrently in family members of patients, but not in the family members of
      normally fertile couples. CONCLUSIONS: Autoimmune diseases occur more frequently
      in the families of women who have experienced recurrent spontaneous abortions.
      Both types of diseases involve genes in the class II region of the major
      histocompatibility complex.

PMID- 7826505
TI  - Association of sperm antibodies with other autoantibodies in infertile men.
AB  - PROBLEM: In many autoimmune diseases there is an increased incidence of other
      autoantibodies. However, the incidence of other autoantibodies in patients with
      seminal sperm antibodies is unknown. The most widely used tests to detect seminal
      and serum sperm antibodies are the mixed antiglobulin reaction (MAR) and the Tray
      agglutination test (TAT). METHOD: We therefore determined the incidence of
      antinuclear, antimitochondrial, thyroid peroxidase, and thyroglobulin antibodies,
      and rheumatoid factor in 147 patients investigated with MAR and 157 patients
      investigated with TAT. RESULTS: TAT positive patients had a significantly
      elevated incidence of antinuclear antibodies (chi 2 test, P < 0.005) and
      thyroglobulin antibodies (chi 2 test, P < 0.001). Thyroglobulin antibodies were
      increased in patients with MAR IgG > 40% and also significantly (chi 2 test, P <
      0.05) increased in MAR IgA positive patients. Furthermore, thyroid peroxidase
      antibodies were only found in TAT positive patients. CONCLUSIONS: The
      consistently increased incidence of thyroid autoantibodies in infertile patients
      with sperm antibodies may indicate an increased risk for the development of
      autoimmune thyroid disease. This finding therefore suggests screening of patients
      with immunologic infertility for autoimmune thyroid disease and a further
      evaluation of the prognostic and pathophysiologic significance of thyroid
      autoantibodies in immunologic infertility.

PMID- 7826506
TI  - Immunization of mice against a synthetic N-terminal extracellular domain
      gonadotropin-releasing hormone receptor peptide: evidence for a direct uterine
      effect.
AB  - PROBLEM: Immature male and female mice were immunized with a synthetic peptide
      corresponding to amino acids 5-17 (ASLEQDPNHCSAI) of the mouse hypophyseal
      gonadotropin-releasing hormone (GnRH) receptor. METHOD: Effect of immunization
      (postpuberal) was restricted to the uterus. Pituitary-gonadal functions were not
      altered. RESULTS: The endometrial lining of immunized females was thin and lacked
      glandular development. These observations were corroborated in actively immunized
      and passively immunized adult females. CONCLUSIONS: Apparently endometrial cells
      express a unique surface antigen, though reactive with antipeptide antibodies,
      that differs from the prototype pituitary GnRH receptor. Antibodies that
      selectively inhibit endometrial maturation might be used to treat proliferative
      diseases of the uterus.

PMID- 7826507
TI  - Effects of muscimol applied to the basolateral amygdala on acquisition and
      expression of contextual fear conditioning in rats.
AB  - The amygdala is known to be important for normal aversive Pavlovian learning in
      the rat. The relative contribution of the amygdala to the learning vs.
      performance of conditional fear with the GABAa agonist muscimol was assessed.
      Rats were prepared with cannulas aimed at the basolateral amygdala and trained in
      a contextual fear conditioning paradigm in which each subject received a series
      of footshocks in a distinctive observation chamber. Conditional responses evoked
      after exposure to the observation chamber were assessed 24 hr later. Rats that
      were pretreated with muscimol before performance showed a significantly
      attenuated fear response, and injections made before acquisition resulted in a
      much smaller decrement in conditional fear measured 24 hr after training. These
      results indicate that acquisition-related processes that may be occurring within
      the amygdala are more difficult to disrupt than those associated with
      performance.

PMID- 7826508
TI  - Context, conditioning, and hippocampal rerepresentation in animal learning.
AB  - The researchers argue that a previous computational account of hippocampal region
      function in associative learning (M. Gluck & C. Myers, 1993) has emergent
      implications that accurately describe the role of the hippocampal region in
      contextual processing. This article unifies 2 seemingly conflicting views of
      contextual processing: It accords contextual cues no special representational
      status (e.g., R. Rescorla & A. Wagner, 1972), yet it also allows context to stand
      in a superordinate relationship to the cues it contains (e.g., L. Nadel & J.
      Willner, 1980). As a result, the account correctly expects that context can
      develop occasion-setting properties and that context shifts can weaken learned
      responses or attenuate latent inhibition. The article also explains data
      suggesting that hippocampal lesions reduce contextual sensitivity. It may help
      unify several previous theoretical accounts of the hippocampal region's role in
      contextual processing.

PMID- 7826509
TI  - Impairment in shifting attention in autistic and cerebellar patients.
AB  - MRI and autopsy evidence of early maldevelopment of cerebellar vermis and
      hemispheres in autism raise the question of how cerebellar maldevelopment
      contributes to the cognitive and social deficits characteristic of autism.
      Compared with normal controls, autistic patients and patients with acquired
      cerebellar lesions were similarly impaired in a task requiring rapid and accurate
      shifts of attention between auditory and visual stimuli. Neurophysiologic and
      behavioral evidence rules out motor dysfunction as the cause of this deficit.
      These findings are consistent with the proposal that in autism cerebellar
      maldevelopment may contribute to an inability to execute rapid attention shifts,
      which in turn undermines social and cognitive development, and also with the
      proposal that the human cerebellum is involved in the coordination of rapid
      attention shifts in a fashion analogous to its role in the coordination of
      movement.

PMID- 7826510
TI  - Hippocampal and amygdaloid involvement in nonspatial and spatial working memory
      in rats: effects of delay and interference.
AB  - Parametric manipulations of the task demand were used to examine the role of the
      hippocampus and amygdala in nonspatial and spatial working memory in rats.
      Hippocampal lesions produced an immediate and long-lasting impairment of
      nonspatial working memory in an operant task. The memory deficits increased as
      the delay interval and the amount of proactive interference increased.
      Hippocampal lesions severely impaired spatial working memory in spatial
      alternation. Extensive postoperative testing reduced the magnitude of impairment
      of nonspatial but not spatial working memory. Amygdaloid lesions did not impair
      any aspect of performance in 2 tasks. The results suggest that the hippocampus,
      but not the amygdala, is involved in working memory and the task demand is a
      critical determinant for observing impairments of nonspatial working memory
      following hippocampal lesions.

PMID- 7826511
TI  - Working memory, response selection, and effortful processing in rats with medial
      prefrontal lesions.
AB  - This study examined the effects of lesions of the prelimbic area of the rat
      prefrontal cortex on acquisition and retention of nonmatching (NMTS) and matching
      to-sample (MTS) tasks. Both tasks involved a reference and a working memory
      component, but only working memory was impaired by the lesions. A comparison of
      the 2 tasks revealed quantitatively similar deficits in postoperatively trained
      rats. In preoperatively trained rats, however, the deficits were more important
      in the MTS task than in the NMTS task. In addition, an effect of interference
      between successive trials was observed in the NMTS task but not in the MTS task.
      Perseverative tendencies were observed in the MTS task only. These results
      suggest that prefrontal lesions induce working memory deficits as a result of
      poor temporal encoding and increased susceptibility to interference and impair
      effortful processing, such as that engaged in response selection mechanisms.

PMID- 7826512
TI  - Medial septal lesions in rats produce permanent deficits for strategy selection
      in a spatial memory task.
AB  - Rats with medial septal (MS) lesions have been shown to consistently use a
      stereotypic response strategy rather than a nonstereotypic spatial learning
      strategy when solving a radial maze task. The present study examined the long
      term effects of MS lesions on spatial memory performance to determine whether MS
      lesions permanently impair rats from using a nonstereotypic strategy. Male rats,
      initially trained on a radial maze, were given either MS or sham surgeries and
      were subsequently retested on the maze. Consistent with previous studies, all
      rats with MS lesions used a stereotypic strategy during the postoperative retest.
      However, when placed through a series of retraining phases that required the rat
      to use a nonstereotypic strategy to solve the task, none of the MS rats could
      solve the task. These results indicate that lesions of the medial septum produce
      permanent spatial memory deficits that cannot be restored through extensive
      behavioral training.

PMID- 7826513
TI  - Working memory tasks in five-choice operant chambers: use of relative and
      absolute spatial memories.
AB  - Rats were trained to nose poke into illuminated holes to perform 1 of 2 different
      spatial working memory tasks (relative recency or reward history) in a 5-choice
      operant chamber. A series of experiments indicated that choice accuracy on both
      tasks depended on (a) the holes' spatial separation, and (b) their relative
      rather than absolute positions. The results suggest that accurate choice depended
      on using a motor mediation strategy to turn, so as to encounter the target
      (correct) hole before encountering the alternative (wrong) hole. The drugs
      administered to the rats, d-amphetamine, scopolamine, and CGP-37849 impaired
      choice accuracy on these tasks, even though task performance had not appeared to
      depend on explicit memory for the sample responses. This suggests that parallel
      drug effects obtained on other operant matching- or nonmatching-to-position tasks
      may not have reflected truly amnesic effects of the drug treatments.

PMID- 7826514
TI  - Acquisition of conditional discriminations in hippocampal lesioned and
      decorticated rats: evidence for learning that is separate from both simple
      classical conditioning and configural learning.
AB  - This study examined whether hippocampal or neocortical lesions would impair
      acquisition of a discrimination task using taste aversions. Rats were injected
      with a drug 15 min before a flavored solution-lithium chloride pairing. On
      alternate days, vehicle injections preceded and followed access to the same
      flavored solution. Rats learned to consume significantly more of the flavored
      solution after vehicle injections than after drug injections. Rats with
      hippocampal lesions or neonatal decortication performed as well as controls. Rats
      with hippocampal lesions also learned a similar task in which visual and textural
      cues predicted whether access to a flavored solution would be followed by an
      injection of lithium chloride or vehicle. However, these hippocampal lesions did
      impair performance in the Morris water task. Occasion setting may involve a type
      of learning dissociated from both simple classical conditioning and configural
      learning.

PMID- 7826516
TI  - NMDA receptor antagonist MK-801 blocks learning of conditioned stimulus
      unconditioned stimulus contiguity but not fear of conditioned stimulus in
      goldfish (Carassius auratus L.).
AB  - The blockade of learning of Pavlovian fear conditioning by the N-methyl-D
      aspartic acid (NMDA)-receptor antagonist MK-801 was examined in 166 goldfish. In
      previously untrained fish, MK-801 blocked learning of a light-off or a tone
      conditioned stimulus (CS) paired with an electrical shock unconditioned stimulus
      (US). Pretraining on the light-off CS did not affect the rate of learning of the
      tone CS but protected the tone learning from disruption by MK-801. Switching from
      the light-off to the tone CS changed the identity of the CS but not its temporal
      contiguity with the US. Pretraining consisting of pseudoconditioning of the light
      off CS did not protect subsequent tone learning from blockade by MK-801. Thus,
      the NMDA receptor functions are necessary for learning related to the temporal
      contiguity of the CS and US but not to the identity of the CS as a cue to the
      occurrence of the fearful effects of the US.

PMID- 7826515
TI  - Spatial localization in the Morris water maze in rats: acquisition is affected by
      intra-accumbens injections of the dopaminergic antagonist haloperidol.
AB  - Previous studies (G. E. Ploeger, B. M. Spruijt, & A. R. Cools, 1992) showed that
      low doses of systemically injected haloperidol affected spatial learning in the
      Morris water maze. This study investigated effects of intra-accumbens injections
      of haloperidol on spatial learning. To control for motivation and sensorimotor
      coordination, the researchers trained the rats to escape onto a visible platform.
      Low doses (50-100 ng) of haloperidol impaired spatial learning, whereas escaping
      on a visible platform was undisturbed. The 500-ng dose of haloperidol completely
      blocked acquisition because of combined learning and motor impairments. Retrieval
      of an acquired escape response was unaffected by 500 ng haloperidol. The data
      show that mesolimbic dopaminergic activity is involved in the acquisition of
      spatial localization. The results are related to studies demonstrating the
      involvement of the nucleus accumbens in cue-directed behaviors.

PMID- 7826517
TI  - Classical conditioning of opioid activity in the fetal rat.
AB  - Milk promotes activity in the kappa opioid system of the rat fetus that reduces
      responsiveness to cutaneous stimulation. In this study, fetuses on Gestational
      Day 20 were presented with an artificial nipple (conditioned stimulus; CS) paired
      with an intraoral infusion of milk (unconditioned stimulus; US). One paired
      presentation of the CS and US reduced fetal responsiveness after reexposure to
      the CS. Selective antagonism of opioid receptors after conditioning indicated
      that reduced responsiveness was due to mu opioid activity. Mu and kappa opioid
      activity was evident after 3 paired presentations of CS and US and reexposure to
      milk. Kappa opioid activity during conditioning was necessary for mu involvement
      after reexposure to the CS or US. These experiments, which were conducted with
      fetal subjects that lacked suckling experience, suggest that neurochemical
      systems engaged during suckling may change rapidly after the newborn's initial
      experiences at the nipple.

PMID- 7826518
TI  - Paradoxical autonomic responses to aversive stimuli in the developing rat.
AB  - The goals of this research were to determine (a) the change in heart rate
      elicited by aversive auditory stimuli in the laboratory rat at different ages and
      (b) the autonomic origins of those changes at each age. The results of the first
      2 experiments showed that aversive white noise stimuli elicited cardiac
      deceleration in preweanling (16-day-old) rats and cardiac acceleration in
      weanling (23-day-old), periadolescent (30-day-old), and adult (60-day-old) rats.
      Subsequent experiments showed that (a) the decrease in heart rate elicited by the
      noise stimulus in preweanling rats was mediated by parasympathetic activation of
      the heart, (b) the stimulus-elicited increase in heart rate elicited by the noise
      in periadolescent rats was mediated by parasympathetic withdrawal of the heart,
      and (c) the noise-induced increase in heart rate in adult rats was primarily
      mediated by sympathetic activation of the heart.

PMID- 7826521
TI  - Estrogen and estrogen-progesterone treatments counteract the effect of
      scopolamine on reinforced T-maze alternation in female rats.
AB  - The purpose of the experiments was to determine if steroid hormone treatments
      would attenuate the effect of the muscarinic receptor blocker scopolamine on a
      memory task. Ovariectomized rats were trained first to alternate for food reward
      between the arms of a T maze. Following training, females treated with
      scopolamine hydrobromide (0.2 mg/kg ip) did not alternate correctly between the
      arms of the T maze and responded at chance levels. However, when estradiol
      benzoate (25 micrograms) was administered 72, 48, and 24 hr before testing alone
      or in combination with progesterone (500 micrograms) administered 4-6 hr before
      testing, females alternated successfully between the arms of the T maze following
      scopolamine administration. Results indicate that gonadal steroids can completely
      counteract the impairment of T maze performance induced by scopolamine in female
      rats.

PMID- 7826520
TI  - Amiloride sensitivity in the neonatal rat.
AB  - Amiloride-sensitive sodium channels in taste buds appear to play a key role in
      the response to NaCl stimulation, at least in adult rats. The researchers
      examined whether neonatal rats, which display an exaggerated preference for
      hypertonic NaCl solutions, lack functional amiloride-sensitive sodium channels.
      NaCl intake was significantly reduced by amiloride pretreatment, but water and
      ammonium chloride, NH4Cl, were unaffected. The researchers assessed whether the
      early appearance of amiloride sensitivity was mediated by effects on chorda
      tympani (CT) activity by sectioning the CT before testing. CT transection reduced
      intake of NaCl solutions and eliminated evidence of amiloride sensitivity.
      Amiloride sensitivity was also assessed by recording of whole-nerve CT activity
      at 8-11 days of age; the response to NaCl stimulation was significantly
      suppressed by amiloride. These data indicate that amiloride-sensitive sodium
      channels develop earlier than previously believed.

PMID- 7826519
TI  - Tegmental pedunculopontine lesions in rats decrease saccharin's rewarding effects
      but not its memory-improving effect.
AB  - The tegmental pedunculopontine nucleus (TPP) of the brainstem has been identified
      as a critical substrate for both opiate and food reward in nondeprived rats. In
      this study of rats, TPP lesions blocked saccharin-conditioned place preferences,
      in both the presence and the absence of water deprivation. TPP lesions also
      attenuated the unconditioned intake of saccharin and water over several hours
      after recovery from food and water deprivation. TPP lesions did not block
      saccharin preferences over water in short-duration tests. The researchers propose
      that the absence of a lesion effect may reflect previously conditioned
      discriminations. TPP lesions had no effect on the ability of posttrial
      presentations of a 3.2% saccharin solution to improve lithium-chloride
      conditioned taste aversions. TPP lesions dissociate 2 behavioral processes
      elicited by saccharin: One mediates unconditioned-reward-conditioned-reinforcing
      effects, and another mediates the memory-improving effect.

PMID- 7826522
TI  - Spectral sensitivity, photopigments, and color vision in the guinea pig (Cavia
      porcellus).
AB  - Behavioral discrimination tests and electroretinogram (ERG) flicker photometry
      were used to measure spectral sensitivity and to define the spectral mechanisms
      of the guinea pig (Cavia porcellus). Results from these 2 approaches converge to
      indicate that guinea pig retinas contain rods with peak sensitivity of about 494
      nm and 2 classes of cone having peak sensitivities of about 429 nm and 529 nm.
      The presence of 2 classes of cones suggests a retinal basis for a color vision
      capacity. Behavioral tests of color vision were conducted that verified this
      prediction: Guinea pigs have dichromatic color vision with a spectral neutral
      point centered at about 480 nm. The cone pigment complement of the guinea pig is
      different from that known to characterize other rodents.

PMID- 7826523
TI  - Efficacy trials of AIDS vaccines: how science can inform ethics.

PMID- 7826524
TI  - Immuno-contraception.

PMID- 7826525
TI  - Recent developments in immunotoxin therapy.
AB  - Immunotoxin (IT) research has been ongoing for 15 years. During the past 2 years,
      work has focused on several areas: on improvements and developments in first- and
      second-generation ITs; the preparation of new immunotoxin constructs with anti
      tumor activity; novel animal models for preclinical evaluation of immunotoxins;
      and clinical trials, which are now entering Phase II or III in humans.

PMID- 7826526
TI  - Recent developments in the radioimmunotherapy of cancer.
AB  - Recent trials using radiolabeled monoclonal antibodies, particularly for
      hematologic neoplasms, have demonstrated the ability of these agents to destroy
      tumor cells safely and specifically. Advances in molecular biology, immunology
      and radiochemistry will allow the continued development of strategies to overcome
      the remaining obstacles to effective therapy with radioimmunoconjugates.

PMID- 7826527
TI  - Tumor immunotherapy: the tumor cell as an antigen-presenting cell.
AB  - Increased knowledge in basic immunology has led to a variety of innovative and
      imaginative approaches for tumor-specific immunotherapy. One of these approaches
      is based on the premise that tumor cells do not normally stimulate an effective
      tumor-specific immune response, because they do not efficiently present tumor
      antigens to the relevant lymphocytes. To overcome inadequate antigen
      presentation, it has been hypothesized that tumor cells can be genetically
      engineered to present tumor peptides directly to T lymphocytes.

PMID- 7826528
TI  - Heat shock protein-peptide complexes in cancer immunotherapy.
AB  - Heat shock proteins (HSPs) are associated with a broad spectrum of peptides
      derived from the cells from which they are isolated. Vaccination with such HSP
      peptide complexes elicits protective immunity against tumors or other cells used
      as the source of HSPs. These observations suggest that HSP-peptide complexes are
      suitable as vaccines against cancers and infectious diseases.

PMID- 7826529
TI  - MHC class II restricted tumor antigens and the role of CD4+ T cells in cancer
      immunotherapy.
AB  - Recent studies in human and murine systems suggest a central role for CD4+ T
      cells in initiating, effecting and maintaining anti-tumor immunity.
      Characterization of the tumor-associated antigens recognized by CD4+ T cells may
      prove critical to the success of cancer immunotherapy strategies.

PMID- 7826530
TI  - Immunology of the human papilloma virus in relation to cancer.
AB  - Human papillomaviruses (HPVs) have been associated with benign and malignant
      epithelial proliferations in either skin or mucosa. Two HPV oncogenic proteins,
      E6 and E7, are important in the induction and maintenance of cellular
      transformation and are co-expressed in the majority of HPV-containing carcinomas.
      Therefore, vaccines targeted to these proteins may provide an opportunity to
      prevent and treat HPV-associated malignancies. The encouraging results from
      recent experimental vaccination systems in animal models suggest that continued
      exploration in these systems might lead to trials on human subjects and might
      allow us to prevent HPV infection or control its potentially life-threatening
      consequences.

PMID- 7826531
TI  - Cytokines and the Th1/Th2 paradigm in transplantation.
AB  - With studies elucidating the cytokine programs associated with T-cell activation,
      allograft rejection and tolerance induction, the Th1/Th2 paradigm has become a
      unifying model to explain the observed cytokine profiles. The proof that these
      cytokines mediate allograft tolerance, however, is at best indirect. More recent
      studies highlighting the redundant and pleiotropic nature of cytokine networks
      suggest that the Th1/Th2 paradigm may not be sufficient to explain fully the
      mechanisms underlying allograft tolerance.

PMID- 7826532
TI  - Prospects for xenografting.
AB  - New insights into the mechanisms of hyperacute rejection, endothelial cell
      activation and accommodation are clarifying the processes that determine the
      rejection of discordant xenografts. Recent advances include the identification of
      endothelial cell antigens targeted by human anti-pig antibodies and an increasing
      understanding of the mechanisms underlying endothelial cell activation. Novel
      ways to prevent hyperacute rejection, including new therapeutic agents and the
      use of organs from transgenic animals, are promising to significantly improve the
      early survival of pig organs transplanted into man. Clinical xenotransplantation
      has become a realizable goal.

PMID- 7826533
TI  - Chronic graft rejection.
AB  - Although chronic rejection remains the most crucial cause of organ graft loss
      over the long term, its etiology is not well defined. Early injury to graft
      endothelial cells caused by alloantigen-independent factors, such as ischemia or
      reperfusion, as well as alloantigen-dependent events, such as acute rejection,
      have been implicated. Macrophages and their products, peptide growth factors and
      adhesion molecules are all thought to play an important role in this process via
      the cytokine-adhesion molecule cascade. Although new immunosuppressive agents,
      including RS61443 or rapamycin, may be effective in preventing antigen-driven
      components of this condition, risk factors for initial non-immune injury must
      also be considered and, if possible, countered.

PMID- 7826534
TI  - What can be done to prevent graft versus host disease?
AB  - Graft versus host disease presents a major obstacle to the widespread application
      of allogeneic bone marrow transplantation despite improvements in drug
      prophylaxis. Although animal models are providing an understanding of the biology
      of the process, opportunities for exploitation of that knowledge for therapeutic
      purposes are still limited. One way to overcome this impasse is to build on the
      positive benefits of T-cell purging of marrow, by combining it with intelligent
      correction of the known negative effects.

PMID- 7826535
TI  - Which way for drug-mediated immunosuppression?
AB  - The basic immunosuppressive protocol involves the use of multiple drugs, each
      directed at a discrete site in the T-cell activation cascade. The prevailing
      paradigm regarding the mechanisms of action of immunosuppressants is that they
      function to prevent allograft rejection by preventing cell activation,
      proliferation and/or cytokine production. A new hypothesis is that some of the
      immunosuppressants might function by stimulating the expression of
      immunosuppressive molecules and/or cells.

PMID- 7826536
TI  - The induction of tolerance to alloantigens using HLA-based synthetic peptides.
AB  - The identification of immunomodulatory approaches that allow the induction of
      antigen-specific unresponsiveness is required for long-term graft survival
      without the complications of chronic immunosuppression. Recent novel strategies
      based upon treatment with synthetic peptides corresponding to linear sequences of
      MHC class I and II molecules reproducibly induce tolerance to alloantigens.
      Although the mechanisms involved are still not completely understood, the
      phenomenology reported makes these approaches promising for evaluation in
      clinical trials.

PMID- 7826537
TI  - Cancer.

PMID- 7826538
TI  - Transplantation.

PMID- 7826539
TI  - Changes in psychiatric caring values in Finland.
AB  - A shift from institutional to non-institutional caring systems took place in
      Finnish psychiatric care in the 1980s. This article describes the values related
      to caring and the changes that occurred during the time span of a decade in a
      ward that rehabilitates mental patients as non-institutional care in northern
      Finland. The changes in patient and staff values are examined by studying the
      changes in caring practices in the ward. The ethnonursing method developed by
      Leininger (1995, 1991) was used to examine the rehabilitation of psychiatric
      patients. Data were collected by interviewing twenty patients and eleven staff
      members. Results demonstrated that by the 1980s individualism was increasingly
      valued and personal freedom and self realization were more valued than hard work
      and solidarity. People's values shifted from universality to greater diversity.
      Transcultural nursing implications are discussed.

PMID- 7826540
TI  - The tribes of nursing in the USA culture of nursing.

PMID- 7826541
TI  - Time to celebrate and reflect on progress with transcultural nursing.

PMID- 7826542
TI  - Culturally competent care: visible and invisible.

PMID- 7826543
TI  - Impressions of nursing in China.
AB  - This is the first of a series of reflections on a trip a group of nurses made to
      China in June 1994. John Douglas, a science writer who accompanied the group,
      wrote the first article in this series. He shares his reflections on the Chinese
      health care system and interviews conducted with several Chinese nurses. Dr.
      Grayce Roessler, an internationally known transcultural nursing leader, directed
      the tour. She has traveled extensively in China (some 30 trips over twenty years)
      and has worked with Chinese nurses to establish transcultural educational
      exchange programs between the United States and China. In a future issue of this
      journal, Dr. Roessler will present her reflections on nursing in China from a
      transcultural nursing leader's perspective. In the final article in this series
      Dr. Julianna Finn, a transcultural nurse educator who also made this trip, will
      present some reflections on nursing in China from a transcultural nursing
      theoretical perspective using Leininger's Culture Care Theory.

PMID- 7826544
TI  - Transcultural clinical nursing incidents: what do you think? What would you do?

PMID- 7826546
TI  - Information on certification and recertification of transcultural nurse
      specialists.

PMID- 7826545
TI  - President's message: our literature reflects themes of culture care universality
      and diversity.

PMID- 7826547
TI  - The lived experience of Native Americans with diabetes within a transcultural
      nursing perspective.
AB  - The purpose of this study was to advance transcultural nursing knowledge based on
      the lived experiences of Native Americans with non-insulin dependent diabetes
      mellitus (NIDDM). The phenomenological qualitative research method was used to
      discover Native Americans lived experiences. Data was gathered in rural Oklahoma
      through non-structured interviews and clinical observations of Native Americans
      with NIDDM. The interviews were transcribed and analyzed for themes and patterns
      of similar statements among informants. Six major thematic categories were
      identified: reactions to NIDDM, responses to loss of health, identification with
      others, fear associated with the disease process, peace related to the diagnosis
      of NIDDM, and grieving associated with the diagnosis of NIDDM. The informants'
      experiences were reconstructed into transformed meanings that characterized the
      lifeworld of Native Americans with NIDDM.

PMID- 7826548
TI  - Modern strategies to prevent coronary sequelae and stroke in hypertensive
      patients differ from the JNC V Consensus Guidelines.
AB  - In recent years, government agencies of many countries have established consensus
      guidelines for the evaluation and treatment of hypertension. Once published,
      guidelines tend to be perceived as directives by a variety of health care
      providers. Unfortunately, these guidelines often do not reflect the practices of
      most hypertension experts. This report summarizes the opinions of seven
      hypertension experts concerning the impact of "official" guidelines on clinical
      practice. In addition, the individual therapeutic recommendations of these panel
      members are summarized. Their different treatment strategies reflect the
      diversity of first rate treatment plans that aim to reduce the cardiovascular
      sequelae in individual patients with essential hypertension. Most importantly,
      not one of these seven treatment strategies followed the "preferred" treatment of
      the U.S. guidelines, which recommend diuretics and beta-blockers as first-line
      therapy. The present authors approach the treatment of hypertension as a means to
      reduce cardiovascular events. Thus, reduction of blood pressure is not the most
      important therapeutic endpoint. The panel believes that whereas many different
      drugs can produce effective blood pressure reduction, the modern primary goal of
      antihypertensive drug therapy is to select a regimen most likely to prolong the
      quality and duration of life. In real terms, this means that the primary goal of
      treatment is the prevention of the major vascular sequelae of hypertension (heart
      attack, ventricular remodeling, hypertrophy, heart failure, and stroke) that
      shorten useful life. There are a number of effective hypertensive treatments,
      which can be selected based on individual patient requirements. However, many
      consensus guidelines do not allow the flexibility required to optimize individual
      patient treatment. As a result, health care providers should not feel compelled
      to regard the preferences of "official" guidelines as the best, modern, state-of
      the-art therapy for an individual patient. All seven experts who are deeply
      involved in the daily care of patients preferred drugs other than beta-blockers
      and diuretics (the Joint National Committee [JNC] choices) for first-line therapy
      of hypertension.

PMID- 7826549
TI  - Guidelines for treating hypertension: improved care or retarded progress?
AB  - A number of national and international bodies have published guidelines for the
      management of hypertension. Although there is general agreement on certain
      aspects of treatment, there are also significant differences (for instance, in
      the threshold blood pressure for drug treatment, the target blood pressure, and
      selection of drugs for initial monotherapy). Apparent consensus has been reached
      despite absence of definitive evidence and despite overlapping membership of some
      groups responsible for the guidelines. The composition of guidelines for
      nonexperts is a valuable exercise but its limitations and potential dangers
      should be clearly defined.

PMID- 7826550
TI  - Oil and water? Economic advantage and biomedical progress do not mix well in a
      government guidelines committee.
AB  - This article examines the results of the Joint National Committee's Fifth Report
      on the treatment of hypertension (JNC-V), especially regarding the economic
      arguments put forth therein. Economics are a poor basis for treatment decisions,
      as the cheapest therapies may not be the best for any given patient. Broad
      treatment guidelines based on economic motives will result in poorer patient care
      and less valuable medical research.

PMID- 7826551
TI  - Renin and aldosterone are higher and the hyperinsulinemic effect of salt
      restriction greater in subjects with risk factors clustering.
AB  - Separate lines of evidence suggest that abdominal obesity, insulin, and renin are
      independent risk factors for coronary heart disease. Since insulin levels are
      higher in abdominally obese subjects and may enhance renin and aldosterone
      production, these risk factors may not be entirely independent. Moreover, the
      renin-angiotensin system may contribute to insulin resistance. These observations
      suggest that some inconsistencies in the literature regarding the effects of salt
      restriction on insulin may be explained by baseline anthropometric and metabolic
      differences in the subjects studied. To examine these issues, 29 volunteers with
      a range of risk factors were studied after 1 week each on isocaloric 20 and 200
      mmol/day NaCl diets. Measurements included ambulatory blood pressures, plasma
      renin and aldosterone, and responses to oral glucose and intravenous insulin.
      Subjects were divided into three groups based on a composite score reflecting the
      risk factor cluster associated with abdominal obesity and hyperinsulinemia. The
      nine subjects with the highest scores had significantly greater values for renin
      and aldosterone on both the high and low salt diets than the nine subjects with
      the lowest scores. Fasting insulin and triglycerides, the insulin response to
      oral glucose, and plasma aldosterone all rose significantly more with salt
      restriction in the high than in the low risk subjects. Plasma renin activity also
      tended to increase more on the low salt diet in the high risk group. Ambulatory
      blood pressures were greater on the low than the high salt diet only in the high
      risk group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7826552
TI  - Plasma renin activity and insulin sensitivity in normotensive subjects.
AB  - Insulin sensitivity in essential hypertension and atherosclerosis has elicited
      substantial research interest. Hyperinsulinemia in prospective studies identifies
      patients at risk for the development of coronary atherosclerosis. Plasma renin
      activity has also been shown to predict myocardial infarction, and correlates
      inversely with insulin sensitivity in hypertensive patients. The current study
      investigated the relationship between plasma renin activity and insulin
      sensitivity in 25 normotensive subjects. Using the euglycemic clamp technique,
      the data show a significant inverse correlation between supine plasma renin
      activity and insulin-mediated glucose uptake (r = -0.44; P = .027). Significant
      relationships were also found between plasma renin activity and fasting insulin
      concentration and fasting serum triglycerides. Reductions in relative skeletal
      muscle blood flow during insulin infusion have been reported in insulin-resistant
      compared to insulin-sensitive subjects. Skeletal muscle is the main site of
      insulin action during euglycemic clamp study and angiotensin II increases
      skeletal muscle blood flow. Increasing plasma renin activity may reflect a
      metabolic compensation which offsets the relative reduction in insulin-mediated
      enhancement in skeletal muscle blood flow in insulin resistance by generation of
      angiotensin II, which in turn promotes skeletal muscle blood flow.

PMID- 7826553
TI  - Angiotensinogen dependency of blood pressure in two high-renin hypertensive rat
      models.
AB  - In this analysis we investigated whether angiotensinogen (Aogn) levels were
      related to blood pressure (BP) in two hypertensive rat models when renin
      secretion was either under physiologic regulation or out of control. These
      relationships were investigated using BP data from previous reports in which
      SHRsp and Dahl S rats were studied for 10 to 12 weeks while ingesting a high-salt
      diet with and without the angiotensin II (AngII) antagonist losartan. During the
      first 4 weeks of high-salt diet, plasma renin concentration (PRC) was
      appropriately suppressed but it subsequently increased paradoxically in both
      strains. During the first 4 weeks, when renin secretion was under normal control,
      as indicated by its suppression by the high-salt diet and by an inverse
      relationship between PRC and BP (r = -0.69, P < .001 and r = -0.53, P < .01 in
      Dahl S and SHRsp, respectively), there was no relationship between BP and plasma
      Aogn. In contrast, when renin secretion increased paradoxically, the inverse
      relationship between BP and PRC was lost and a positive relationship was found
      between BP and plasma Aogn in both Dahl S rats (r = 0.70, P < .01) and SHRsp (r =
      0.57, P < .01). There was no relationship between BP and Aogn in either strain
      during treatment with losartan either before or after 4 to 6 weeks of salt
      feeding. These results show Aogn dependency of BP, but only under conditions in
      which renin cannot feed back normally. The Aogn relationship to BP was most
      likely dependent on the vasoconstrictor effect of AngII since it was lost during
      AngII AT1 receptor antagonism.

PMID- 7826554
TI  - Cardiovascular actions of atrial natriuretic factor in sheep with cardiac
      failure.
AB  - The present study examines in detail the short-term cardiovascular actions of
      atrial natriuretic factor (ANF) in sheep with experimental low-output cardiac
      failure. Five conscious sheep, surgically implanted with a ventricular pacing
      wire, were paced at 220 beats/min for 14 days. Most clinical symptoms of
      congestive heart failure (CHF) were apparent after the 14 days, characterized by
      low cardiac output, high venous pressure, increased total peripheral resistance,
      increased plasma levels of ANF, noradrenaline, arginine vasopressin and renin,
      and marked fluid retention. On day 14 of pacing, intravenous infusion of ANF at
      100 micrograms/h for 60 min restored cardiac output to prepacing values and
      reduced both total peripheral resistance and right atrial pressure. These effects
      were sustained throughout the infusion period. No change was seen in blood
      pressure, plasma renin, or noradrenaline levels. These hemodynamic changes,
      produced by short-term infusion of ANF, contrasted with those seen in normal
      sheep, where there was a fall in cardiac output with increased total peripheral
      resistance. These changes reflect a return toward normal of the left ventricular
      function curve. This is the first study to report that ANF improves cardiac
      function in conscious sheep with CHF, primarily by a vasodilator action to reduce
      cardiac preload, and suggests that ANF may be useful in treating the hemodynamic
      effects associated with cardiac failure.

PMID- 7826555
TI  - Dissociation of renin and aldosterone during low-dose epinephrine infusion.
AB  - Besides its dose-dependent alpha- and beta-adrenoceptor-mediated vascular action,
      hormonal effects of epinephrine also involve the activation of renin secretion by
      direct stimulation of renal beta 1-adrenoceptors. To determine the interrelation
      between increased plasma renin activity in response to epinephrine and plasma
      aldosterone concentration and renal excretion of potassium and sodium, 26 normal
      subjects were subjected to 4 h of an intravenous infusion of low-dose epinephrine
      (12 ng/kg/min). Epinephrine infusion raised mean plasma epinephrine concentration
      2.8-fold above control (P < .001). Plasma renin activity (PRA) increased by 56%
      (P < .01) during epinephrine infusion, whereas plasma aldosterone concentration
      remained constant. Infusion of epinephrine also resulted in markedly suppressed
      urinary potassium excretion (-32%; P < .025), while urinary sodium excretion was
      not altered. Serum potassium was decreased by 4.1% during epinephrine (P < .025).
      Systolic blood pressure and heart rate did not change, and diastolic blood
      pressure was slightly reduced by 5 mm Hg (P < .025). In summary, during low-dose
      epinephrine infusion PRA is markedly increased while plasma aldosterone remains
      unchanged. The fall in urinary potassium excretion in the presence of reduced
      serum potassium concentration is most likely mediated via the beta-adrenoceptor
      mediated shift of potassium into cells. This in turn may prevent a concomitant
      rise of plasma aldosterone, which subsequently contributes to the blunted
      kaliuresis and unchanged natriuresis found during the epinephrine-induced rise of
      PRA. In conclusion, the epinephrine-induced fall in serum potassium appears to be
      the predominant regulator of plasma aldosterone concentration even in the
      presence of a stimulated PRA.

PMID- 7826556
TI  - Preservation of left ventricular function and coronary flow by angiotensin I
      converting enzyme inhibition in the hypertensive-diabetic Dahl rat.
AB  - The effect of the angiotensin I-converting enzyme (ACE) inhibitor benazepril (55
      mg/kg orally) on the preservation of cardiac performance in diabetic-hypertensive
      Dahl S rats was investigated. Diabetes mellitus was produced by streptozotocin.
      Fasting (4-h) blood glucose levels were 279 +/- 50 mg/dL in diabetic Dahl salt
      sensitive v 79 +/- 5 mg/dL in nondiabetic Dahl salt-sensitive rats. Cardiac
      performance was determined at the end of 8 weeks in an isolated perfused working
      heart apparatus. Peak left ventricular pressure (LVPmax), left ventricular peak
      negative dP/dt, and coronary flow were depressed in diabetic Dahl S rats (P < or
      = .05 v control). These deficits in cardiac function were not observed in
      diabetic Dahl S rats chronically treated with benazepril. The beneficial effects
      of benazepril apparently were independent of systolic blood pressure reduction.
      Although plasma ACE activity was increased in diabetic Dahl S rats, plasma renin
      activity was reduced. This suggests that the beneficial effects of ACE inhibition
      may be due to an effect upon the kinin system rather than the renin-angiotensin
      system. The benazepril-associated preservation of cardiac function in this study
      suggests that ACE inhibitors may be beneficial in the treatment of diabetic heart
      disease.

PMID- 7826558
TI  - Postpartum blood pressure and insulin sensitivity in African-American women with
      recent preeclampsia.
AB  - Pregnancy-induced hypertension and preeclampsia are relatively common in
      nulliparous, inner-city, African-American, pregnant women and contribute to
      considerable maternal, fetal, and neonatal morbidity and mortality in that
      population. Recently, insulin resistance has been related to the development of
      hypertension in young African-Americans and hyperinsulinemia and elevated insulin
      to-glucose ratios, suggesting insulin resistance, have been demonstrated in women
      with preeclampsia. To investigate whether insulin resistance existed postpartum
      and, therefore, independently of the pregnant state, the hyperinsulinemic,
      euglycemic technique was used 3 to 6 months postpartum to assess insulin
      sensitivity in 10 young, black, primiparous, inner-city women with recent
      preeclampsia and seven age-, weight- and body-mass-index-matched black women with
      healthy pregnancies. The age, weight, body-mass index, waist-to-hip ratio, the
      duration since parturition, and fasting plasma glucose and insulin were similar
      in the preeclamptic and control groups. During the clamp procedure, the insulin
      levels and mean diastolic blood pressure and mean arterial pressure were also
      similar for both groups; however, the mean systolic blood pressure of the
      preeclamptic group (123 +/- 3 mm Hg) was higher than that of the control group
      (114 +/- 2 mm Hg) (P < .05). Insulin-stimulated glucose disposal was not
      different between the preeclamptic (5.6 +/- 0.3 mg/kg/min) and control groups
      (5.7 +/- 0.7 mg/kg/min). This suggests that the elevation in postpartum systolic
      blood pressure may reflect a persistent abnormality of blood pressure homeostasis
      which is not associated with insulin resistance.

PMID- 7826557
TI  - Lack of effectiveness of a low-sodium/high-potassium diet in reducing
      antihypertensive medication requirements in overweight persons with mild
      hypertension. TAIM Research Group. Trial of Antihypertensive Interventions and
      Management.
AB  - The Trial of Antihypertensive Interventions and Management (TAIM) was a
      multicenter randomized drug (double-blind, placebo-controlled)-diet trial. One
      objective of TAIM was to assess the long-term ability of a low-sodium/high
      potassium (Na+ decreases/K+ increases) diet to maintain blood pressure control in
      persons at 110% to 160% ideal weight with diastolic blood pressure from 90 to 100
      mm Hg who were on no drugs or on low-dose monotherapy. Participants, 56% men and
      33% black, were randomized to usual diet (n = 296) or to Na+ decreases/K+
      increases diet (n = 291) and within each diet group to placebo, 25 mg/day
      chlorthalidone, or 50 mg/day atenolol. Treatment failure was defined as lack of
      blood pressure control requiring additional drugs according to specified
      criteria. At baseline, the mean value for age was 48 years; blood pressure,
      143/93 mm Hg; weight, 88 kg; and 24-h urinary sodium and potassium excretion
      rates, 133 and 57 mmol/day, respectively. At 3 years, the net difference in 24-h
      urinary sodium/potassium excretion rates between the Na+ decreases/K+ increases
      and the usual diet groups was -30 and +11 mmol/L/day. The relative risk of
      treatment failure for Na+ decreases/K+ increases compared to usual diet by
      proportional hazards regression was 0.95 (P = .71). This study provides no
      support for the sole use of a low-sodium/high-potassium diet as a practical
      therapeutic strategy in maintaining blood pressure control in the moderately
      obese.

PMID- 7826559
TI  - Ambulatory blood pressure and heart rate in adolescents with insulin-dependent
      diabetes mellitus.
AB  - There is little information regarding ambulatory blood pressure in adolescents
      with insulin-dependent diabetes. Twenty-four-hour ambulatory blood pressure and
      heart rate was studied in 28 normotensive adolescents with insulin-dependent
      diabetes mellitus (IDDM) and normoalbuminuria, and adolescent controls.
      Ambulatory heart rate was higher during day and night (P = .001) in the IDDM
      patients, with normal mean diurnal variation of heart rate and blood pressure.
      Duration of diabetes related to diastolic ambulatory blood pressure (r = 0.69, P
      = .0001) and diastolic blood pressure burden (r = 0.61, P = .0001) independent of
      age, gender, height, body mass index, metabolic control, and albumin excretion
      rate. The ambulatory blood pressure monitor was well accepted in patients and
      controls. Ambulatory blood pressure monitoring in adolescents detects early
      changes in relation to duration of insulin-dependent diabetes.

PMID- 7826560
TI  - Good data needs good statistics.

PMID- 7826561
TI  - Can antihypertensive drugs reduce atherosclerosis and its clinical complications?
AB  - Several classes of antihypertensive drugs, including beta-blockers, angiotensin
      converting enzyme (ACE) inhibitors, calcium antagonists, alpha 1-blockers, and a
      combined calcium antagonist/alpha 1-blocker, have been shown to reduce
      atherosclerosis in hypercholesterolemic animals. Although the exact mechanism of
      action of these drugs has not been described, certain findings are of particular
      interest. All of these drugs have the ability to inhibit cellular growth. ACE
      inhibitors appear to be antiatherosclerotic in several species including the low
      density lipoprotein (LDL)-deficient Watanabe heritable hyperlipidemic rabbit, and
      their effects appear to be mediated through both angiotensin II inhibition and
      bradykinin enhancement. Calcium antagonists may influence primarily the
      development of new atherosclerotic lesions and their action may be species
      specific and, at least in part, dependent on the integrity of the LDL receptor.
      The action of alpha 1-blockers and of a combined calcium antagonist/alpha 1
      blocker in hypercholesterolemic animals is probably related in part to their
      cholesterol-lowering properties. Whether any of the antihypertensive drugs can
      affect atherosclerosis in humans remains to be determined. Clinical trials are in
      progress to examine their effects on the course of coronary heart disease and on
      surrogate endpoints of atherosclerosis such as those demonstrable by angiography
      and Doppler-ultrasound techniques. Although the results of trials involving such
      surrogate markers will be of great interest, the findings will need to be
      interpreted with caution because they may not necessarily be predictive of either
      the course of atherosclerosis or its clinical complications.

PMID- 7826562
TI  - New therapeutic trends in calcium antagonism. Are they meaningful?
AB  - Recent advances in the field of calcium antagonism include the development of
      long-acting calcium antagonists, some of which have a slow onset of action. Some
      of these newly developed calcium antagonists are dihydropyridine derivatives.
      Others, including monatepil (AJ-2615), are chemically unrelated to either the
      dihydropyridine (nifedipine), phenylalkylamine (verapamil), or benzothiazepine
      (diltiazem) prototypes of the group. Irrespective of their chemistry, however,
      vascular selectivity is a prominent feature of the more recently developed
      calcium antagonists. This, coupled with their long duration and slow onset of
      action, properties that facilitate continuous protection rather than the
      intermittent protection of short-acting calcium antagonists, makes them suitable
      for use as blood pressure-lowering agents that provide "vascular protection"--as
      indicated by their ability to slow experimentally induced atherosclerotic lesion
      formation. Long-acting vasculoprotective calcium antagonists can be used to treat
      other disorders, including angina pectoris. Their efficacy as antiatherosclerotic
      agents, proven in experimental models, needs to be confirmed by clinical trials
      on natural atherosclerosis.

PMID- 7826563
TI  - Antihypertensive, antiatherosclerotic, and plasma lipid-lowering effects of
      monatepil, a novel calcium antagonist with alpha 1-adrenoceptor-blocking activity
      in experimental animals.
AB  - Traditional antihypertensive therapy has been shown to reduce the incidence of
      hypertension-related vascular injuries; however, it is not fully effective
      against cardiovascular abnormalities. In some animal models, calcium antagonists
      have been demonstrated to possess antiatherogenic properties but to have no
      effects on plasma lipid levels, whereas alpha 1-adrenoceptor blockers have been
      shown to reduce plasma lipid levels. Monatepil is a new type of calcium
      antagonist that also has alpha 1-adrenoceptor-blocking activity. Therefore, it is
      thought that monatepil may have both antiatherosclerotic and plasma lipid
      lowering effects in addition to its slow-onset and long-lasting antihypertensive
      effect. To determine the antiatherosclerotic effects of monatepil, we examined
      its effect on experimental atherosclerosis induced by feeding a high-cholesterol
      diet to monkeys, whose lipid metabolism resembles that of humans. Monatepil, at a
      daily dose of 30 mg/kg, at which plasma levels are equivalent to those in
      clinical antihypertensive therapy, was administered orally for 6 months.
      Monatepil suppressed elevation of cholesterol in the aorta and reduced the
      atherogenic (sudanophilic) area. Histologic examination revealed that monatepil
      treated monkeys exhibited little aggregation of foam cells in either the aorta or
      coronary arteries compared with vehicle-treated atherogenic monkeys. In addition,
      monatepil showed preventive effects against increases in total cholesterol and
      low density lipoprotein (LDL), and against decreases in high density lipoprotein
      in plasma caused by cholesterol loading. The plasma lipid-lowering effect may be
      mediated through up-regulation of the number of hepatic LDL receptors by the
      alpha 1-adrenoceptor-blocking activity, and the antiatherosclerotic effect may be
      produced by the combined calcium antagonist, alpha 1-adrenoceptor-blocking, and
      antilipid peroxidation activities. In summary, monatepil is an antihypertensive
      agent belonging to a new class with antiatherogenic properties and the ability to
      reduce plasma lipid levels.

PMID- 7826564
TI  - The efficacy of monatepil, a new calcium antagonist, in the treatment of
      essential hypertension.
AB  - A multicenter, open-label trial in Japan examined the efficacy, safety, and
      optimal dose of monatepil (AJ-2615) as monotherapy and in combination therapy
      with angiotensin-converting enzyme (ACE) inhibitors or beta-blockers. Patients
      with essential hypertension who had never been treated or had been refractory to
      conventional antihypertensive agents were enrolled in the trial. During a 4-week
      control period patients assigned to monotherapy received placebo and those
      assigned to combination therapy received an ACE inhibitor or beta-blocker and
      placebo. Patients with systolic blood pressure (BP) > or = 160 mm Hg and
      diastolic BP > or = 95 mm Hg at the end of the control period were enrolled in
      the study. The initial dose of monatepil was 30 mg/day in monotherapy and 15
      mg/day in combination therapy; the daily dose was titrated to 60 mg/day according
      to the antihypertensive response. The treatment period was 8 to 12 weeks. Blood
      pressure decreased from 168 +/- 8/100 +/- 6 to 142 +/- 9/85 +/- 7 mm Hg (SD) with
      monatepil monotherapy, from 171 +/- 11/102 +/- 6 to 141 +/- 9/84 +/- 6 mm Hg in
      combination with ACE inhibitors, and from 175 +/- 13/102 +/- 7 to 153 +/- 21/91
      +/- 9 mm Hg in combination with beta-blockers (P < .001). When patients in whom
      mean BP decreased by > or = 13 mm Hg were defined as responders, the response
      rate was 80.4%, 78.1%, and 51.6% in the respective groups.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7826565
TI  - Coronary heart disease and hypertension.
AB  - Coronary disease is a frequent outcome of hypertension. Although clinical trials
      with conventional antihypertensive agents have shown that the incidence of other
      complications of hypertension, such as stroke or congestive heart failure, is
      reduced as predicted, they have failed to show the expected reductions in
      coronary events. A partial explanation may lie in the fact that hypertension
      typically consists of a syndrome of inherited metabolic and cardiovascular
      abnormalities, and treatment that focuses primarily on blood pressure control
      without taking into account other factors that contribute to atherosclerotic
      disease can have only limited protective effects. The coronary hypothesis in
      hypertension extends this reasoning into three separate components. First is an
      intrinsic tendency to excessive proliferative and hypertrophic activity within
      vascular tissue, presumably reflecting growth-promoting activity stimulated by
      increased endocrine and local paracrine effects; next is the impact of the
      commonly encountered concomitant risk factors, including high blood pressure,
      that exaggerate and accelerate development of underlying atherosclerotic lesions;
      and finally hemodynamic factors, including increased variability and sustained
      elevations of blood pressure, that can destabilize vascular lesions and
      precipitate acute events. Treatment of these hemodynamic factors in elderly
      patients whose underlying vascular changes are already well advanced is likely to
      reduce vascular endpoints effectively, but a broader-based therapeutic approach
      is required for younger patients, in whom the ongoing proliferative and risk
      factor aspects of their potential coronary disease must also be targeted.

PMID- 7826566
TI  - Noninvasive quantitative evaluation of early atherosclerosis and the effect of
      monatepil, a new antihypertensive agent. An interim report.
AB  - In two studies on the same group of patients we evaluated noninvasive methods of
      assessing atherosclerosis and determined the effect of the new calcium channel
      blocking agent monatepil on the progression of early atherosclerosis in humans.
      Computed tomography (CT) of the lower abdominal aorta and ultrasonography of the
      carotid arteries were used as noninvasive methods to determine the extent of
      atherosclerosis. To evaluate the CT images, we developed a new medical image
      analysis program. This enabled aortic calcification volume (ACV) to be quantified
      using plain CT images, and aortic wall volume (AWV) and aortic wall and
      calcification volume (AWCV) to be quantified from contrast CT images.
      Interobserver coefficients of variation of ACV, AWV, and AWCV (n = 8) were 4.7,
      2.4, and 5.0%, respectively. In the monatepil study, the effect of the drug on
      serum lipid profiles was evaluated. Preliminary results show that shortly after
      monatepil administration, total serum cholesterol levels decreased significantly
      from 253.8 +/- 35.6 to 244.8 +/- 38.6 mg/dL (P < .009) and triglyceride levels
      tended to decrease. A positive correlation between the change in total
      cholesterol and changes in mean platelet volume was found (P = .028). Fasting
      immunoreactive insulin levels decreased in the four patients in which they were
      determined. Although this is a preliminary study, results indicate that CT of the
      lower abdominal aorta in combination with our new analysis program may be a
      precise, reproducible means of assessing early atherosclerosis. We have also
      shown that monatepil significantly decreases total cholesterol levels. However,
      the long-term effects of monatepil on the progression of atherosclerosis remain
      to be determined.

PMID- 7826567
TI  - Comparative effects of monatepil, a novel calcium antagonist with alpha 1
      adrenergic-blocking activity, and nitrendipine on lipoprotein and carbohydrate
      metabolism in patients with hypertension.
AB  - The effects of monatepil, a new calcium antagonist with alpha 1-blocking
      activity, and nitrendipine on lipoprotein and carbohydrate metabolism in 86
      patients with mild-to-moderate hypertension were examined in a randomized, open
      label, multicenter (32 hospitals) study. Thirty-nine patients treated with
      monatepil and 33 patients treated with nitrendipine completed the 12-week study.
      Monatepil and nitrendipine each significantly decreased both systolic and
      diastolic blood pressure. Changes in heart rate were not seen in either group.
      Monatepil administration significantly decreased total cholesterol, low density
      lipoprotein (LDL) cholesterol, the LDL cholesterol to high density lipoprotein
      (HDL) cholesterol ratio, apolipoprotein (Apo) B levels, and HbA1c levels, whereas
      no changes in these measurements were observed in nitrendipine-treated patients.
      Monatepil also significantly decreased lipoprotein(a) levels, but there were no
      significant changes in HDL cholesterol, Apo-AI, or Apo-E levels. After
      nitrendipine treatment, the C peptide concentration decreased significantly,
      although no significant changes were observed in fasting blood glucose or
      immunoreactive insulin levels. On the basis of these results, it can be concluded
      that monatepil belongs to a new class of antihypertensive calcium antagonist with
      favorable carbohydrate metabolism and lipid-lowering activity, although the
      clinical importance of these findings has not been established.

PMID- 7826568
TI  - Fluoxetine at anorectic doses does not have properties of a dopamine uptake
      inhibitor.
AB  - Although fluoxetine is a highly selective inhibitor of serotonin uptake in vitro
      and in vivo, some investigators have suggested that dopamine uptake inhibition
      may contribute to anorectic actions of fluoxetine. The present experiments were
      done to determine fluoxetine's effects in some animal protocols in which dopamine
      uptake inhibitors have characteristic actions. Mazindol prevented the depletion
      of striatal dopamine and its metabolites by amphetamine in iprindole-pretreated
      rats, but fluoxetine had no effect. Mazindol prevented the depletion of striatal
      dopamine and its metabolites by 6-hydroxydopamine injected
      intracerebroventricularly into rats, but fluoxetine had no effect. Mazindol
      enhanced the elevation of 3,4-dihydroxyphenylacetic acid concentration in rat
      brain after spiperone injection, but fluoxetine did not cause that effect.
      Fluoxetine did not mimic amfonelic acid in antagonizing the retention of alpha
      methyl-m-tyramine invant striatum after the injection of alpha-methyl-m-tyrosine.
      These results show that fluoxetine, at doses that are effective in blocking the
      serotonin uptake carrier and causing anorexia, does not block the dopamine uptake
      carrier.

PMID- 7826569
TI  - The 5-HT1A receptor antagonist (S)-UH-301 blocks the qR)-8-OH-DPAT-induced
      inhibition of serotonergic dorsal raphe cell firing in the rat.
AB  - (S)-UH-301 [(S)-5-fluoro-8-hydroxy-2-(dipropylamino)-tetralin, 0.5-4.0 mg/kg
      i.v.] did not significantly alter the firing rate of 5-hydroxytryptamine (5-HT)
      containing neurons in the dorsal raphe nucleus (DRN) as a group, although some
      individual cells were activated whereas others were depressed. However, (S)-UH
      301 (2.0 mg/kg i.v.) consistently reversed the inhibition of DRN-5-HT cells
      produced by the selective 5-HT1A receptor agonist (R)-8-OH-DPAT (0.5 microgram/kg
      i.v.) and the dose-response curve for this effect of (R)-8-OH-DPAT was markedly
      shifted to the right by pretreatment with (S)-UH-301 (1.0 mg/kg i.v.). These
      results support the notion that (S)-UH-301 acts as an antagonist at central 5
      HT1A receptors.

PMID- 7826570
TI  - Seasonal regulation of melatonin receptors in rodent pars tuberalis: correlation
      with reproductive state.
AB  - Using quantitative autoradiography, we have studied the relationship between
      melatonin receptor density in the pars tuberalis (PT) and photoperiodic changes
      in sexual activity in a photoperiodic (Syrian hamster), and a non photoperiodic
      (rat) rodent. Syrian hamsters exposed to short photoperiod (SP) for 13 weeks or
      kept in long photoperiod (LP) with daily melatonin injections for 8 weeks, had
      both gonadal regression and a significant decrease in 2-125I-melatonin binding
      site density in the PT when compared to controls. In contrast, when the animals
      were sexually active, photorefractory Syrian hamsters exposed to SP for 27 weeks,
      or rats kept for 13 weeks in SP, the PT melatonin receptor density was similar to
      that of control animals kept in LP. These results show clearly that a correlation
      exists between gonadal status and density of melatonin receptors in the PT and
      suggest that the PT could be the site where melatonin mediates its effects on
      seasonal function.

PMID- 7826571
TI  - Behavioral significance of phasic changes in mesolimbic dopamine-dependent
      electrochemical signal associated with heroin self-injections.
AB  - High-speed chronoamperometry with monoamine-selective carbon fiber electrodes was
      used in rats to monitor, during 5-6 consecutive daily sessions, changes in DA
      dependent electrochemical signal in the nucleus accumbens (NAcc) during
      intravenous heroin (0.1 mg/kg) self-administration (SA) behavior and passive
      repeated drug injections performed with a temporal scheme similar to that in the
      SA experiment. In trained animals, biphasic signal fluctuations time-locked to
      the individual lever-presses were found to accompany all but the first daily SAs.
      The signal gradually increased by 30-40 nM for the 10 minutes preceding the SA,
      reached a peak at the moment of lever-press and decreased abruptly by
      approximately 40 nM for 3-4 min after heroin SA. The cycle then repeated,
      reaching a new peak at the moment of the next lever-press. Rapid bi-directional
      fluctuations in signal associated with individual heroin SAs were superimposed on
      substantial tonic increase in signal baseline (400-500 nM). This increase quickly
      developed after presentation of heroin-related light cue and the first SA, was
      relatively stable during all subsequent SAs and decreased towards the baseline
      after the last SA of a session. Changes in signal baseline induced by repeated
      heroin SAs depended strongly upon the signal's basal level (r = -0.787); that
      signal preferentially increased when its basal values were low (0-300 nM), and
      decreased when signal was tonically elevated (> 600 nM). Repeated passive heroin
      injections also induced biphasic signal fluctuations and a similar tonic increase
      in signal baseline. Although a transient signal decrease (25 nM for 2-4 minutes)
      followed by a prolonged signal increase occurred after each but not the first
      passive injection, the gradual pre-injection signal acceleration was absent.
      Although DOPAC, a principal DA metabolite, may significantly contribute to the
      tonic increase in electrochemical signal seen during SA session, the changes in
      extracellular DA may be the main contributor to both the rapid signal increases
      preceding drug-taking and the transient signal decreases following heroin SA. If
      so, the present findings suggest that activation of mesolimbic DA cells and
      increase in DA transmission may be involved in the mediation of motivational
      and/or activational components of drug-seeking and drug-taking behavior. An acute
      termination of previous drug- and behavior-associated DA activation with a
      transient inhibition of DA release, immediately following heroin SA may correlate
      with the drug's rewarding action, representing a part of a mechanism regulating
      drug-taking behavior.

PMID- 7826572
TI  - Evidence that ibogaine releases dopamine from the cytoplasmic pool in isolated
      mouse striatum.
AB  - We measured the effect of ibogaine on the tritium efflux from isolated mouse
      striatum preloaded with [3H]dopamine ([3H]DA). Ibogaine increased the basal
      tritium outflow in a concentration-dependent manner, but it was without effect on
      electrical stimulation-induced tritium overflow. Separation of the released
      radioactivity after ibogaine administration showed that this drug increased the
      release of [3H]DA and [3H]-dihydroxyphenylacetic acid ([3H]DOPAC), but the efflux
      of O-methylated-deaminated metabolites was not changed. The dopamine (DA)
      releasing effect of ibogaine was reduced by the DA uptake inhibitors cocaine and
      nomifensine. The tritium efflux evoked by ibogaine was not altered by omission of
      Ca2+ from the perfusion buffer or by inhibition of the voltage-sensitive Na+
      channels with tetrodotoxin. Ibogaine maintained its effect on release from
      superfused striatum prepared from reserpine-pretreated mice. The ibogaine-induced
      tritium release measured from mouse striatum that was preloaded with [3H]DA was
      not affected by the D-2 DA receptor ligands (-)-quinpirole and (+/-)-sulpiride,
      indicating that the ibogaine-induced release is not subject to presynaptic
      autoreceptor regulation. Ibogaine failed to affect [3H]DA uptake and retention in
      mouse striatum. These data indicate that at the nerve terminal level ibogaine
      releases DA, and the primary source for the release is probably the cytoplasmic
      pool. The DA-releasing effect of ibogaine may have importance in mediation of its
      hallucinogenic action, as seen in a frequent practice in African cults.

PMID- 7826573
TI  - Effects of zotepine, haloperidol and clozapine on MK-801-induced stereotypy and
      locomotion in rats.
AB  - In the present study we compared the effects of the atypical neuroleptic zotepine
      to haloperidol and clozapine on stereotypies and locomotion induced in rats by
      the N-methyl-D-aspartate (NMDA) antagonist MK-801. Zotepine caused a dose
      dependent reduction of MK-801-induced stereotypies and locomotion. Zotepine at a
      dosis of 2.5 mg/kg body weight showed a similar effect to 0.25 mg/kg haloperidol
      in reducing stereotypies and locomotion. Clozapine (5.0 mg/kg) reduced
      significantly locomotion and non-significantly stereotypies. These results add
      support to the assumption that MK-801-induced behavior provides an adequate
      animal model to test the potential efficacy of typical and atypical neuroleptics
      in the treatment of psychoses.

PMID- 7826574
TI  - GABA binding sites: their density, their affinity to muscimol and their behaviour
      against neuroactive steroids in human gliomas of different degrees of malignancy.
AB  - The aim of the present investigation was to answer the question if there exists a
      relation between the equipment of human gliomas with GABA binding sites and the
      degree of malignancy of these tumours diagnostically characterized according to
      WHO classification. The following parameters were assessed: the density, the
      affinity and the sensitivity to the modulating steroids 3 alpha-hydroxy-5 alpha
      pregnane-20-one (3 alpha OH-DHP) and 3 alpha,21 dihydroxy-5 alpha-pregnane-20-one
      (THDOC). Scatchard analysis and non linear computerization revealed that the
      occurrence of GABA sites was directly related to the degree of tumour malignancy:
      GABA sites were only detectable in lower malignant gliomas of WHO grade II but
      not in the very malignant glioblastomas. However, irrespective of the individual
      density to be detected all glioma GABA sites were sensitive to 3 alpha-hydroxy-5
      alpha-pregnane-20-one (3 alpha OH-DHP) and 3 alpha,21 dihydroxy-5 alpha-pregnane
      20-one (THDOC) without exception. The effects of THDOC were due to increases in
      the number of binding sites whereas in the presence of 3 alpha OH-DHP a decrease
      in affinity was noted, additionally. These findings support the view of a normal
      functional integrity of GABA receptors in gliomas.

PMID- 7826575
TI  - Validation study of thoracic fluid bioimpedance for assessing the haemodialysis
      induced changes in total body fluids.
AB  - Thoracic fluid bioimpedance (TFB) has been proposed as a noninvasive technique
      for monitoring both haemodynamics and fluid homeostasis in patients on regular
      dialysis. To validate the reliability of TFB in assessing the haemodialysis (HD)
      induced changes in plasma volume (PV) in these patients, we examined the changes
      of TFB during and after HD in relation to those in total plasma protein (TP)
      concentration, haematocrit (Ht), heart rate (HR), total body water (TBW) and
      plasma angiotensin II (A-II) concentration. Data were recorded in 13 HD patients
      with a wide range of interdialytic weight gains before, at the end, and 4, 8, 24,
      48 h after the HD session. We found that the percent TFB changes were closely and
      inversely related with those of TP, Ht and TBW (r = -0.54, r = -0.45 and -0.68,
      respectively, p < 0.001 for all). Similar relations were found between the
      percent changes in TFB and those in absolute TP and Ht. In addition, a direct
      relation was found between the percent changes of TFB and those of HR and of A-II
      (r = 0.33 and r = 0.31, respectively, p < 0.01 for both). These data indicate
      that TFB is a reliable method for evaluating the HD-induced changes of intra- and
      extravascular fluids and, with respect to the conventional techniques, has the
      advantage of providing this information dynamically, and in conjunction with the
      haemodynamic data of patients.

PMID- 7826576
TI  - Comparison of fast peritoneal equilibration tests with 1.36 and 3.86% dialysis
      solutions.
AB  - At present dialysis solutions with different glucose concentrations are used for
      the peritoneal equilibration test (PET) and Fast-PET in peritoneal dialysis (PD).
      We compared the results of two Fast-PETs, using 1.36 and 3.86% solutions
      sequentially in 30 patients on PD treatment, to obtain information on peritoneal
      transport (D/P-4 h) and ultrafiltration rates. Creatinine, phosphorus and urea
      D/P-4 h in the two Fast-PETs were not statistically different, unlike those for
      potassium, beta 2-microglobulin and glucose. The creatinine and phosphorus D/P-4
      h values in particular proved to be uninfluenced by the different dialysis
      solutions. The lack of correlation between the two Fast-PET ultrafiltration
      values confirmed the difficulty in interpreting this parameter, above all in the
      case of non-homologous Fast-PETs. We obtained useful indications for comparing
      different Fast-PET results, but were unable to reach a decisive conclusion
      regarding the best of the two dialysis solutions for this test.

PMID- 7826577
TI  - Continuous arteriovenous hemoperfusion in acute poisoning.
AB  - We have investigated the efficacy of a pumpless hemoperfusion technique,
      continuous arteriovenous hemoperfusion (CAVHP) in 3 cases of acute intoxications
      with meprobamate, theophylline and phenobarbital. Dramatic responses were noted
      in both hemodynamic unstable and comatous patients. With this technique, a blood
      flow of 120 cm3/min could be achieved in severe hypotension. Moreover, with the
      restoration of blood pressure, blood flow increased to 150-400 cm3/min. Our
      preliminary experience has shown that CAVHP allows an exceptionally high solute
      elimination. Hemoperfusion clearances of meprobamate, phenobarbital and
      theophylline were 198 +/- 5.6 cm3/min, 290.25 +/- 25.33 cm3/min and 192.79 +/- 55
      cm3/min, respectively. Our present results suggest that CAVHP is a simple, safe,
      effective and less costly alterative of conventional hemoperfusion.

PMID- 7826578
TI  - Plasma interleukin 8 levels are increased by hemodialysis.
AB  - The effects of hemodialysis on plasma interleukin 8 (IL-8) levels and the
      expression of IL-8 mRNA in peripheral blood mononuclear cells (PBMC) were studied
      in uremic patients undergoing maintenance hemodialysis (HD) using regenerated
      cellulose dialyzers. The plasma IL-8 levels in the patients after HD sessions
      were significantly higher than before HD. Comparison of the IL-8 mRNA levels
      obtained from PBMC before and after HD indicated that the expression of IL-8 mRNA
      was increased by HD. The enhancement of production of IL-8 in PBMC during HD may
      be responsible for inflammatory complications and impaired host defense in HD
      patients.

PMID- 7826579
TI  - Calcium mass balance and behavior of intact immunoreactive parathyroid hormone in
      acetate-free biofiltration: acute and one-year evaluation.
AB  - The present study evaluated calcium mass balance (MB) during acetate-free
      biofiltration (AFB) with a dialysate calcium concentration of 2 mmol/l and
      different ultrafiltration rates (UF; 42.5 ml/min in schedule 1 and 48.5 ml/min in
      schedule 3), and with a calcium concentration of 1.75 mmol/l but an UF of 43
      ml/min (schedule 2). We also examined the effects of these schedules on the
      behavior of intact parathyroid hormone (I-PTH). AFB according to schedule 1 and 3
      achieve a positive calcium MB (8.49 +/- 1.56 and 5.59 +/- 1.06 mmol,
      respectively), while in schedule 2 calcium MB merely balanced (0.07 +/- 2.29
      mmol/l). A significant acute intradialytic I-PTH decrease was observed with all
      schedules; after 1 month, however, predialytic PTH values were unchanged in
      schedules 1 and 3, but worsening was noted in schedule 2. Subsequently, AFB was
      performed for 12 months employing a dialytic schedule (No. 1) involving a
      positive calcium balance. A year later I-PTH was significantly lower, thus
      proving that AFB may play an additional part in controlling secondary
      hyperparathyroidism.

PMID- 7826580
TI  - Biocompatibility of hemodialysis membranes: a study in healthy subjects.
AB  - The effect of blood-membrane interaction on several biocompatibility parameters
      has been investigated. Four groups of healthy subjects underwent sham
      hemodialysis, i.e. the establishment of blood-dialysis membrane contact, but
      without circulating dialysate, using cellulose-based membranes (regenerated
      cellulose and cellulose acetate) or synthetic membranes (polysulfone and
      polyacrilonitrile). Contact between blood and cellulose-based membranes resulted
      in pronounced complement activation and leukopenia whereas contact between blood
      and synthetic membranes induced weak complement reaction. The release of
      granulocytic elastase comparable to that obtained during clinical dialysis seemed
      to correlate directly with the types of membrane used. The gradual increase in
      the level of plasma elastase during blood-membrane contact, as opposed to the
      transient nature of the increase in the levels of complement, suggests that
      different mechanisms are responsible for these reactions. Nutritional
      implications of dialysis membrane bioincompatibility are discussed in the light
      of recently published metabolic data obtained in these subjects.

PMID- 7826581
TI  - Monitoring the activity of glucose oxidase during the cultivation of Aspergillus
      niger using novel amperometric sensor with 1, 1'-dimethylferricinium as a
      mediator.
AB  - 1, 1'-dimethylferricinium (DMF+), a deep blue, and stable mediator, was prepared
      from a water-soluble 1, 1'-dimethylferrocene(DMF):2-hydroxypropyl- beta
      cyclodextrin complex via enzymatic oxidation using immobilised bilirubin oxidase.
      This mediator was superior to other soluble ferrocenes, notably carboxyferrocene,
      in terms of both solubility (110 mM vs 0.5 mM) and oxidation potential (150 mV vs
      300 mV against Ag/AgCl). Although the cyclic voltammogram of DMF+ was
      electrochemically equivalent to DMF, the use of the former resulted in a
      significantly lower background current (< 10 nA vs 30 nA). Because of its higher
      solubility, concentrated stock solutions of DMF+ can be prepared and supplied to
      the electrode. This is of particular importance when the signal is severely
      limited by the rate at which the working electrode can oxidase DMF to DMF+. A
      linear response of current versus units of glucose oxidase (GOD) was obtained up
      to 0.5 unit/ml. The detection limit was estimated to be 0.03 unit/ml and the
      response time was 2.5 min or less. The amperometric system was used successfully
      to follow the GOD activity during the growth of Aspergillus niger a well-known
      GOD producer. The results obtained correlated well with a standard absorbance
      based assay using dichlorophenol-indophenol (DCPIP). The KM of GOD for the
      glucose in the lysate was measured as 38 mM. A reduced response and higher KM (48
      mM) of the cell homogenate, compared to the lysate, illustrated the requirement
      for the DMF+ and glucose to diffuse across the cell membrane to interact with GOD
      in whole cells.

PMID- 7826582
TI  - Regeneration of immobilized antibodies on fiber optic probes.
AB  - The regeneration of antibodies covalently immobilized to an optical fibre surface
      was investigated by dissociation of the antibody-antigen complex with three
      different solvents: (a) an acidic solution (0.1 M glycine hydrochloride in 50%
      (v/v) ethylene glycol, pH 1.75), (b) a basic solution (0.05 M tetraethylamine in
      50% (v/v) ethylene glycol, pH 11.0) and (c) 50% (v/v) ethanol in PBS. The fibres
      coated with polyclonal rabbit anti-goat antibody against a large protein retained
      70% and 65% of the original signal after five consecutive regenerations with
      acidic and basic solvent systems, respectively. The fibres coated with monoclonal
      mouse anti-trinitrobenzene antibody specific for a small organic molecule,
      retained over 90% of the original signal when regenerated with basic and ethanol
      solutions. This study evaluated regeneration and reuse of antibody-coated fibre
      optic biosensors as a means of reducing routine laboratory analysis costs and
      time.

PMID- 7826583
TI  - [Biopharmaceutics and pharmacokinetics. 6. Metabolism].

PMID- 7826584
TI  - [Biopharmaceutics and pharmacokinetics. 7. Excretion].

PMID- 7826585
TI  - Synthesis and antiulcer activity of some (1S, 5R)-2-thiabicyclo (3, 3, 0) oct-5
      ene derivatives.
AB  - The preparation of (1S,5R)-2-Thiabicyclo[3,3,0]oct-6-ene derivatives (Sn;n=0,1,2)
      is described. Spectral and optical data (IR, NMR, Mass, alphaD20) are reported.
      These compounds can be considered as thiaprostacyclin-like derivatives. Studies
      of anti-ulcer activity in comparison with two reference compounds (cimetidine,
      pirenzipine) have shown that all the new compounds own a good anti-ulcer
      activity. Further studies are in progress to establish the mechanisms of their
      action.

PMID- 7826586
TI  - [The mechanism(s) of alpha-(aminoethyl)-gamma-butyrolactone. In vivo studies in
      mice].
AB  - This paper describes the synthesis of alpha-(dimethylaminoethyl)-gamma, gamma
      diphenyl-gamma-butyrolactone 4. The study of convulsions induced, on mice, by
      this compound could show the existence of antiGABAergic and cholinergic action
      components, but, unlike the homologous alpha- (dialkylaminomethil)-gamma
      butyrolactones (with one -CH2- less on the aminoalkyl chain), no antiglycinergic
      component was detected. The effects of atropine on the aminolactone 4 induced
      convulsions (antagonism 5mn and synergy 30 mn after atropine) could suggest an
      activation of the glutamatergic receptors (NMDA), by indirect stimulation of
      their glycinergic site, by the aminolactone 4.

PMID- 7826587
TI  - Synthesis of 1,3,4-thiadiazole-[3,2,-a]-s-triazine-5,7-dithione derivatives and
      their pharmacological evaluation.
AB  - 2-Mercapto-6-phenyl-1,3,4-thiadiazole-(3,2-a)-s-triazine-5,7-dithione (1) was
      converted to 2-[3-carboxyl-2-methyl-1-mercapto]-6-phenyl-1,3,4-thiadiazole-(3,2
      a)-s- triazine-5,6 dithione (2) and 2-thioethanoic acid-6-phenyl-1,3,4
      thiadiazole-(3, 2-a)-s-triazine-5,7-dithione (4). This on reaction with o
      phenylenediamine/ethylenediamine/o-aminophenol/o-aminothiophenol and
      polyphosphoric acid yielded compounds 3 (a-d) and 5 (a-d). The compounds 1,2,4,3
      (a-d) and 5 (a-d) were evaluated for their anti-inflammatory activity against
      carrageenan induced paw oedema. The compounds found potent were further tested
      for their antiwrithmogenic activity in albino mice. Two compounds (2,3c)
      exhibited significant anti-inflammatory activity, also showed protection against
      aconitine induced writhing response, with high approximate LD50 values.

PMID- 7826588
TI  - Studies on arylfuran derivatives. Part III. Synthesis and antibacterial
      properties of arylfurfurylidene-isatin-beta-hydrazones and their Mannich bases.
AB  - A number of N1 - arylfurfurylidene isatin -beta- hydrazones were prepared as
      possible antibacterial agents. They were subjected to Mannich reaction in the
      presence of secondary amines. The hydrazones and their Mannich bases were
      screened for their antibacterial properties against both Gram-negative bacteria.

PMID- 7826589
TI  - Oxytocin and behaviour.

PMID- 7826590
TI  - Troponin T: a new marker for myocardial cell injury.

PMID- 7826591
TI  - AIDS: endocrinologic and metabolic considerations.

PMID- 7826592
TI  - Hepatic and metabolic effects of ethanol: pathogenesis and prevention.
AB  - Mechanisms of the hepatotoxicity of ethanol are reviewed, including effects
      resulting from alcohol dehydrogenase (ADH) mediated excessive hepatic generation
      of NADH and acetaldehyde. Gastric ADH explains first-pass metabolism by ethanol;
      its activity is low in alcoholics and in females and is decreased by some
      commonly used drugs. In addition to ADH, ethanol can be oxidized by liver
      microsomes: studies over the last 25 years have culiminated in the molecular
      elucidation of the ethanol-inducible cytochrome P-450 (2E1) which causes
      metabolic tolerance to ethanol and to various commonly used medications, enhanced
      degradation of testosterone and vitamin A (with vitamin A depletion) and
      selective hepatic perivenular toxicity. The latter results from free radical
      generation and activation of various xenobiotics, causing increased vulnerability
      of the heavy drinker to the toxicity of industrial solvents, anaesthetic agents,
      commonly prescribed drugs, over-the-counter analgesics, chemical carcinogens and
      even nutritional factors such as vitamin A and beta-carotene. Furthermore,
      induction of the microsomal pathway contributes to increased acetaldehyde
      generation which promotes GSH depletion and lipid peroxidation and other toxic
      effects. 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
      polyenylphosphatidylcholine, shown to correct the alcohol-induced hepatic
      phosphatidylcholine depletion and to prevent alcoholic cirrhosis in non-human
      primates.

PMID- 7826593
TI  - Insulin-dependent diabetes mellitus and menstrual dysfunction.
AB  - Disordered reproductive function has long been recognized as a prevalent problem
      among women of reproductive age who suffer from insulin-dependent diabetes
      mellitus (IDDM). Delay in menarchial age is frequently seen if IDDM develops in
      the peripubertal years and some form of menstrual dysfunction is found in nearly
      one-third of all women of reproductive age with IDDM. This review summarizes some
      of the prevailing views regarding the mechanisms through which uncontrolled IDDM
      is thought to disrupt normal hypothalamic-pituitary-gonadal function. Although
      animal studies have suggested that poorly controlled IDDM may adversely affect
      the uterovaginal outflow tract and/or ovarian function, no clinical studies have
      suggested that abnormal uterine or ovarian function underlies the menstrual
      dysfunction observed in young diabetic women. Similarly, pituitary function as
      assessed by basal gonadotrophins and gonadotrophin-releasing hormone (GnRH)
      stimulated gonadotrophin release appears to be normal in young women with IDDM.
      Moreover, although there has been some suggestion that pituitary function may
      decline with increasing duration of diabetes, this issue has not been thoroughly
      investigated. It appears that the oligo/amenorrhea noted in IDDM is principally
      hypothalamic in origin and may represent intermittent (and perhaps reversible)
      failure of the GnRH pulse generator, similar to the situation observed in women
      who engage in endurance training or who suffer from anorexia nervosa. Although
      the exact pathophysiological mechanisms that subserve dysfunction of the GnRH
      neuronal system are not well understood, attention has focused on increased
      central opioidergic activity, increased central dopaminergic activity, and
      central glucose deprivation. In this era of emphasis on tight glycaemic control
      and its impact in preventing diabetes complications, the consequences of IDDM on
      reproductive potential appear to be important and must be included in future
      investigative efforts.

PMID- 7826594
TI  - Treatment of respiratory syncytial virus infections in children.
AB  - Treatment of the infections caused by the respiratory syncytial virus (RSV) has
      varied largely in different centres. Recently, however, management practices have
      become more clear based on a number of studies. An infant with RSV bronchiolitis
      should be hospitalized in case of insufficient oxygenation, as measured by pulse
      oximetry, and additional oxygen should be supplied. Mist treatment and
      physiotherapy are not beneficial. Bronchodilators seem to be the drug of choice
      in most infants with bronchiolitis. Use of corticosteroids has not been supported
      by data received from most studies although they are generally used. Ribavirin
      should be used only with high-risk patients such as immunosuppressed children.
      Despite the common prescription of antibiotics, they should only be given to
      patients with verified bacterial infection. In the future, immunotherapy
      including aerosolized IgG may be an alternative in treatment of RSV infections.
      Until an efficient vaccine is brought to clinical use, the best way to limit
      nosocomial spread of infections is to use cohort nursing and gowns.

PMID- 7826595
TI  - Ursodeoxycholic acid in the treatment of primary sclerosing cholangitis.
AB  - Primary sclerosing cholangitis (PSC) is a cholestatic liver disease characterized
      by inflammation and obliterative fibrosis of bile ducts leading to their
      progressive destruction (1-4). As a consequence, cholestasis with elevated serum
      levels of alkaline phosphatase (AP) and gamme glutamyl transpeptidase (GGT) and
      bilirubin in more advanced disease is the most prominent feature of this disease.
      The diagnosis of PSC is primarily based on endoscopic retrograde cholangiography
      with demonstration of irregular strictures and dilatations. In liver biopsy,
      typical findings are portal and periodical inflammation and fibrosis. Since PSC
      is a focal disease, the characteristic histological findings may or may not be
      seen in a single liver biopsy. The cause of PSC is still unknown. The association
      with histocombatibility antigens indicates that immunological mechanisms may be
      involved but it is still unclear whether the disease is immunogenic.
      Alternatively, bacteria and bacterial toxins from the colon might play a role (3,
      4). In 70% of cases PSC is associated with ulcerative colitis (5) and, therefore,
      in all patients with this intestinal disease who also have elevated levels of
      liver enzymes, a cholangiography should be performed. Recently, in up to 80% of
      patients with PSC anti-neutrophil-cytoplasmatic-antigens (ANCA) were found to be
      elevated (6) and, in future, this test may help to diagnose the disease more
      easily. Up to now, however, the disease is usually diagnosed at a relatively
      advanced stage when the patients have jaundice.

PMID- 7826596
TI  - Atopy: a complex genetic disease.

PMID- 7826597
TI  - Neurotrophins and ciliary neurotrophic factor: their biology and pathology.
AB  - Neurotrophins (NTFs) and ciliary neurotrophic factor (CNTF) induce the
      differentiation of neuronal cells, rescue them from naturally occurring death,
      and trigger neuronal regeneration. The NTFs bind to two classes of cell surface
      receptors, whereas CNTF receptor is composed of three subunits. The functions of
      these polypeptide survival factors with trophic action on nerve cells have
      recently been approached by the targeted disruption of the CNTF, NTF and their
      receptor genes by the homologous recombination technique. The embryonic growth
      and morphogenesis of these gene 'knock-out' mice is normal, but they develop with
      defects in various subsets of the peripheral nervous system, and the homozygous
      mutant mice often die during the early postnatal period. Disturbances in the
      biology of NTFs and CNTF have recently been implicated in the pathogenesis of
      certain common neurodegenerative disorders, such as Parkinson's disease, motor
      neurone diseases, and Alzheimer's disease. Intensive research on their
      pharmaceutical perspective has, therefore, been provoked. All neurotrophins and
      CNTF can now be synthesized on a large scale as biologically active recombinant
      proteins, and several alternatives for their local applications to the target
      tissue have been presented. Their therapeutic potential is discussed.

PMID- 7826598
TI  - Snoring and cardiovascular risk factors.
AB  - The association of snoring with some cardiovascular risk factors was studied
      cross-sectionally by a postal survey among 3750 males aged 40-59 years. In
      univariate analyses, snoring associated statistically significantly (P < 0.01)
      with hypertension, smoking, obesity, heavy alcohol use, physical inactivity,
      dyspnoea, hostility and morning tiredness. In a multiple logistic regression
      model adjusted by age, snoring associated significantly with smoking, obesity,
      physical inactivity, hostility and morning tiredness. When smoking was excluded
      from the multivariate model, alcohol use was also associated significantly with
      snoring. The association of snoring with smoking, and with obesity seemed to be
      almost independent from other studied correlates of snoring. Our results indicate
      that in further studies on predictive value of snoring with regard to coronary
      heart disease and stroke, the associations of snoring with hypertension, smoking,
      obesity, heavy alcohol use, physical inactivity and hostility have to be
      considered, as these risk characteristics may cause confounding effects.

PMID- 7826599
TI  - Compression sonography in the diagnosis of deep venous thrombosis of the leg.
AB  - The value of compression sonography was assessed to reduce the number of
      phlebographies otherwise necessary when deep venous thrombosis (DVT) is suspected
      among hospital patients. Compression sonography was used to study 119 prospective
      hospital patients who were suspected of having DVT of the lower extremity. The
      results were compared to those by phlebography. There were 44 DVTs detected by
      phlebography; ten of these were located only in the calf, below the knee. Of the
      remaining 34 femoropopliteal DVTs 33 were detected by the compression sonography
      technique. It is concluded that the use of compression sonography for primary
      investigation of suspected DVT reduces the number of patients who require
      phlebography to those whose results by compression sonography are negative. In
      our study, this would have represented a decrease of 28%, corresponding to a
      reduction of the total diagnostic costs by 10%.

PMID- 7826600
TI  - Epidemiology of rheumatoid arthritis.
AB  - Rheumatoid arthritis remains the most important form of arthritis seen in
      rheumatological practice in the developed world. It presents some tantalizing
      epidemiological features. It is a relatively rare disease particularly in young
      life. It has a marked female excess in all populations studied. There are
      suggestions that it might be declining in incidence, though the reasons for this
      are unexplained. The geographical distribution of the disease is remarkably
      homogeneous. There is evidence of a genetic factor as witnessed by familial
      aggregation particularly by increased disease occurrence in identical twins;
      though the large majority of such twins remain disease discordant throughout
      life. Whilst undoubtedly one of the most important genetic factors in explaining
      disease occurrence is located in HLA class II, genes encoded in this region are
      neither necessary nor sufficient on their own for disease development. The female
      excess remains unexplained but it suggests a hormonal basis for disease
      development. Factors supporting this hypothesis include the observed protective
      effect of the oral contraceptive pill, the increased risk in women who are
      nulliparous and the increased susceptibility to disease during the first three
      months postpartum. This latter finding may be linked with breast feeding: women
      who have breast fed, particularly after their first pregnancy, have an increased
      risk for disease development. It is possible that this is explained by a massive
      increase in circulating prolactin levels.

PMID- 7826601
TI  - Application of an immunocolloid gold technique for the ultrastructural
      demonstration of IgE-receptor complexes on rat mast cells.
AB  - In previous works using cytofluorometry, we demonstrated a broad range of IgE and
      IgE-receptor levels within individual mast cell populations with a 60 to 80%
      occupancy of the IgE receptors on mast cells by native IgE. This study was
      performed in order to confirm our previous findings using an independent method
      and to visualize the distribution of IgE-receptor complexes on mast cells at an
      ultrastructural level. For this purpose an indirect immunocolloidal gold
      labelling technique has been applied. By counting the number of labelled gold
      particles, a relative measure of IgE-receptor surface expression and IgE
      occupancy of the receptors could be obtained. With respect to mast cell
      morphology and anti-IgE binding specificity criteria, 1% glutaraldehyde + 4%
      paraformaldehyde (1:1, vol/vol) was found to be the best of the seven fixatives
      applied in this study. This technique revealed numerous gold particles on the
      surface of mast cells from barrier-maintained rats (26 +/- 11 per mast cell
      section, mean +/- SD). Increased numbers of gold particles were counted if the
      mast cells were incubated with rat myeloma IgE (20 micrograms/ml) (46 +/- 33 per
      mast cell section, mean +/- SD). There were significantly increased numbers of
      gold particles on the mast cells of rats infected with N. brasiliensis (126 +/-
      30 per mast cell section, mean +/- SD). This indicates that some of the IgE
      receptors (about 50% of the total number of IgE receptors in this case) on mast
      cells were occupied by native IgE and that parasite infection significantly
      increased the number of IgE molecules on the surface of the mast cells. These
      results correspond with the findings we have made using the cytofluorometric
      technique and confirm the large individual variations in the density of IgE
      receptors and IgE among the mast cells of a given cell population. Macrophages,
      lymphocytes and eosinophils, carrying the low-affinity IgE receptors (Fc epsilon
      RII), contained less than 5 (normal rats after incubation in rat IgE) or 10
      (nematode-infected rats) gold particles per cell section. We also observed some
      non-granulated lymphocyte-like cells which bound a large number of gold particles
      after incubation with rat myeloma IgE (20 micrograms/ml), indicating that they
      contained IgE receptors Fc epsilon RI). They were interpreted as mast cell
      precursors which have previously been shown to exist in the peritoneal cavity.

PMID- 7826602
TI  - IgG antibody response in bacterial endocarditis using ELISA with multiple
      antigens.
AB  - By means of enzyme-linked immunosorbent assays (ELISAs) the antibody responses
      were detected in sera from normal persons (n = 275), patients with various types
      of bacteremia (n = 137), and patients with endocarditis (n = 28). Four ELISAs
      were evaluated. As antigens ultrasonic extracts of Staphylococcus aureus,
      Staphylococcus epidermidis, Enterococcus faecalis, and nonhemolytic streptococci
      were used. The antibody levels against S. aureus increased with age, while
      antibodies against the other bacteria showed no age variation. The different
      ELISA systems showed many serological cross-reactions. The ELISA in this limited
      material was 72% successful in identifying cases of bacterial endocarditis caused
      by S. aureus (diagnostic sensitivity 84%; diagnostic specificity 89%), while in
      other cases of bacterial endocarditis it was less successful.

PMID- 7826603
TI  - The influence of endotoxin upon middle ear fibroblasts cultured in normal middle
      ear gas and atmospheric air.
AB  - Otitis media represents a continuum of inflammatory stages frequently in
      association with bacteria and/or endotoxin. Furthermore, the disease is often
      treated with insertion of ventilation tubes, which causes hyperoxia relative to
      the physiological state in the tympanic cavity. The present study was undertaken
      to quantitate the interaction between endotoxin and relative hyperoxia in
      cultures of rabbit middle ear fibroblasts incubated in normal middle ear gas and
      atmospheric air, respectively. Growth was monitored by determination of DNA, cell
      protein and cell division. The synthetic activity was estimated by collagen
      production. The antioxidant defense was determined by measuring the intra-and
      extracellular concentrations of superoxide dismutase (SOD). The results
      demonstrated that hyperoxia significantly impaired the growth of middle ear
      fibroblasts, which was compensated for by addition of endotoxin stimulating the
      growth. The collagen synthesis increased significantly in atmospheric air with a
      synergistic effect of endotoxin. Hyperoxia induced intracellular SOD formation,
      while endotoxin tended to reduce the synthesis. Finally, exposure to atmospheric
      air caused significantly larger amounts of reducing agents extracellularly in
      cultures without endotoxin compared to endotoxin incubated cultures. It is
      suggested that endotoxin possess both synergistic and antagonistic potential as
      regards the effects of relative hyperoxia, and that the interaction between
      endotoxin and hyperoxia may be an important factor in otitis media.

PMID- 7826604
TI  - Increase in CD4+ and CD45RO+ memory T cells in the nasal mucosa of allergic
      patients.
AB  - By means of immunocytochemistry we have investigated subsets of T lymphocytes in
      frozen sections of nasal mucosa from patients with seasonal allergic rhinitis and
      healthy control persons. All participants were subjected to time-course
      provocation during the non-pollen season, and samples were taken during
      provocation as well as during the natural pollen season. Computerized image
      analysis was applied for evaluation of the immunostained lymphocytes. CD45RO+
      memory T cells outnumbered the remaining leukocyte populations in the mucosa of
      both allergic patients and controls on all occasions. During the repeat
      provocation there was no difference in numerical values, with respect to any of
      the five leukocyte subpopulations studied (CD4, CD8, CD25, CD45RA and CD45RO),
      between patients and controls. However, during continuous exposure in the pollen
      season a significant increase in CD4+ cells was observed in allergic patients
      compared to before provocation (p < 0.05). No changes were observed with respect
      to CD8+ and CD25+ cells. Similarly, an increase in CD45RO+ memory was found in
      allergic patients during the pollen season compared to the non-pollen season (p <
      0.02). This latter finding was, however, only evident in the patients who did not
      use nasal corticosteroids. Hence the present investigation has demonstrated an
      allergen-induced increase in CD4+ and CD45RO+ memory T cells in the mucosa of
      allergic patients during the pollen season. These events may constitute a
      cellular basis for local continuous production of certain cytokines, particularly
      interleukin-4, which is essential for IgE synthesis.

PMID- 7826605
TI  - Helicobacter pylori infection and fasting serum gastrin levels in a series of
      endoscopically diagnosed gastric polyps.
AB  - The occurrence of H. pylori infection and the levels of fasting serum gastrin
      (SEGA) were examined in 97 patients with different morphological types of
      endoscopically diagnosed gastric polyps. According to the histology of the polyps
      the series was divided into three groups: inflammatory polyps (43 cases), polyps
      with foveolar hyperplasia (25 cases), and hyperplastic polyps including adenomas
      (29 cases). The prevalence of H. pylori infection was significantly lower in
      patients with hyperplastic polyps (45%) and foveolar hyperplasia (48%) than in
      the group with inflammatory polyps (81%). SEGA levels were higher in patients
      with hyperplastic polyps (mean +/- sd: 335 +/- 298 pmol/l) and foveolar
      hyperplasia (183 +/- 216) than in patients with inflammatory polyps (89 +/- 127).
      Signs of so-called "autoimmune" gastric, i.e. corpus atrophy and presence of
      parietal cell antibodies, were commonly found in patients with hyperplastic
      polyps and foveolar hyperplasia, but rarely in patients with inflammatory polyps.
      These results suggest that the polyps with hyperplastic changes (hyperplastic
      polyps and foveolar hyperplasia) are in some of the cases closely related to
      autoimmune gastritis. The presence of corpus atrophy, hypoacidity and various
      types of metaplasia, which characterizes autoimmune gastritis, could explain the
      low prevalence of H. pylori and the high SEGA levels found in these patients.

PMID- 7826606
TI  - Increased mineral dust-induced production of reactive oxygen species by blood
      monocytes from patients with malignant diseases.
AB  - Mononuclear leukocytes were isolated from the peripheral blood of 15 patients
      with malignant pulmonary diseases, 17 patients with pulmonary infections, 18
      patients with chest film abnormalities of non-malignant, non-infectious etiology,
      and 15 healthy persons. The cells were exposed to zymosan yeast, BCG vaccine,
      quartz, or chrysotile asbestos, and the subsequent production of reactive oxygen
      species (ROS) was measured by luminol-dependent chemiluminescence. All the
      stimulants caused significantly higher ROS production in the patient groups than
      in the healthy control group, and the asbestos-induced ROS production was
      significantly more pronounced in the cancer group than in the two non-cancer
      patient groups combined. After one-year follow-up, 5 of the 15 cancer patients
      were alive, and these patients had significantly lower mineral dust-induced ROS
      responses at the time of diagnosis than were found in the patients who died. This
      result was verified in a subsequent study comprising 19 patients with malignant
      pulmonary disorders (6 alive after one year). In conclusion, monocytes from
      patients with malignant diseases seem to be primed for an increased ROS
      production, and high ROS responses seem to correlate with a poor one-year
      survival of the patients.

PMID- 7826607
TI  - Early entry of plasma proteins into damaged neurons in brain infarcts. An
      immunohistochemical study on experimental animals.
AB  - Entry of plasma proteins into damaged neurons has previously been demonstrated in
      various pathological conditions, but little is known about brain infarcts in this
      respect. In the present study, focal ischemic lesions were produced in rats by
      permanent occlusion of the middle cerebral artery (MCA). The animals were killed
      from 1 to 48 h postlesion. Leakage of plasma proteins across the blood-brain
      barrier into the infarcted area was visualized with immunostaining 2-3 h after
      the occlusion. This is earlier than in most previous reports. Entry of plasma
      proteins into ischemic neurons was seen 3 h after permanent occlusion of the MCA,
      while reliable changes were not seen until 12-24 h in sections stained with
      hematoxylin and eosin (H & E). Ischemic neurons stained for plasma proteins
      irrespective of their morphological appearance. Even cells that appeared normal
      with H & E staining were positively labeled. The technique may be used to
      diagnose very early ischemic lesions.

PMID- 7826608
TI  - Anti-CD4 monoclonal antibody treatment in combination with total lymphoid
      irradiation and cyclosporin A in hamster-to-rat cardiac transplantation.
      Morphological features of heart grafts, recipient spleens and lymph nodes.
AB  - Significantly prolonged graft survival (GS) of hamster hearts transplanted
      heterotopically into rats can be achieved by different immunosuppressive
      treatment strategies. The exact mechanism of graft rejection is unclear, but it
      seems to be a primarily humoral, antibody-mediated type of rejection. The
      histopathology of long-term surviving grafts is controversial and the morphology
      of lymphoid tissue in spleens and lymph nodes as the possible site of anti-donor
      antibody formation has not previously been investigated. This report demonstrates
      a significantly prolonged GS in hamster-to-rat cardiac transplantation after
      combined treatment with total lymphoid irradiation (TLI), cyclosporin A (CyA) and
      anti-CD4 monoclonal antibodies (MAb), where long-term GS (> 100 days) could be
      achieved in a few animals. The histopathology of heart grafts showed
      predominantly chronic vascular changes with endothelial proliferation, intimal
      thickening and vessel obliteration. No substantial cellular reactivity in terms
      of mononuclear/lymphoid cell infiltration could be demonstrated in rejected
      grafts. Spleens and lymph nodes were characterized by a profound global reduction
      in lymphoid tissue after preoperative TLI. Although subsequent lymphoid
      regeneration was depressed due to postoperative immunosuppression, a significant
      increase in IgM-positive plasma cells was observed, supporting evidence of an
      antibody-mediated mechanism of graft rejection. The role of CD4+ cells is
      unclear, but anti-donor antibody formation might involve T-cell help.

PMID- 7826609
TI  - p53 immunohistochemical positivity as a prognostic marker in intracranial
      tumours.
AB  - The frequency and scale of positive p53 immunohistochemistry in 107 intracranial
      tumours of different types was studied as a possible prognostic marker using a
      polyclonal antibody CM-1 which detects both the wild-type and mutated p53
      proteins. Fifty of the tumours (46.7%) showed nuclear p53 positivity with
      different percentages of positive nuclei. The positivity was concentrated in
      glial tumours of which 52.8% were positive. Forty-two of seventy-four
      astrocytomas (56.8%), 4 of 12 oligodendrogliomas (33.3%), and 1 of 3 ependymomas
      (33.3%) showed p53-positive nuclei. Cytoplasmic positivity, found in 25
      astrocytomas, was always associated with nuclear positivity. Some p53-positive
      nuclei were seen in 16.7% of the non-gliomatous tumours, but in all cases p53
      positivity was seen in less than 1% of the nuclei. The patients with astrocytomas
      containing more than 5% p53-positive nuclei were younger (mean 27.3 years) (p =
      0.016) and their tumours larger in diameter (mean 4.4 cm) (p = 0.05) than those
      with p53-negative astrocytomas (mean 41.0 years and mean 3.3 cm, respectively).
      In p53-positive (> or = 1% of nuclei) grade IV astrocytomas, survival time was
      significantly shorter (mean 7.2 months) than in p53-negative grade IV
      astrocytomas (mean 15.5 months (p = 0.024). The results indicate frequent p53
      expression in intracranial tumours, especially in gliomas. The association of p53
      positivity with young age, larger tumour size, and poor prognosis in high-grade
      astrocytomas suggests that p53 may be involved in the development of more
      aggressive types of intracranial tumours. According to these results, p53
      immunohistochemical positivity may serve as a prognostic marker in high-grade
      astrocytomas.

PMID- 7826610
TI  - Mycoplasma contamination of chlamydiae isolated from clinical specimens.
AB  - Ten Chlamydia pneumoniae strains were screened for Mycoplasma contamination using
      two differently designed Mycoplasma-specific polymerase chain reactions (PCR).
      The primers of the Mycoplasma-specific PCR designed by Spaepen et al. (9) cross
      reacted with all of the C. pneumoniae strains giving false-positive results. When
      the 10 strains of C. pneumoniae were tested for mycoplasmas with the PCR designed
      by Harasawa et al. (5), only 3 were positive. Mycoplasmas were cultured from
      these three C. pneumoniae strains confirming the latter PCR results. The PCR of
      Harasawa et al. (5) was highly specific for mycoplasmas and did not cross-react
      with C. pneumoniae. These findings suggest that chlamydiae should be periodically
      screened for Mycoplasma contamination. Careful attention to primer design is
      important if PCR is chosen as the screening method.

PMID- 7826611
TI  - Detection of Chlamydia trachomatis in individual and pooled endocervical and
      urethral scrapes by a commercially available polymerase chain reaction.
AB  - The aim of this study was to compare a commercially available PCR kit (Amplicor,
      Roche) with our present routine analysis (SYVA EIA) for the detection of genital
      C. trachomatis infection in females. Furthermore, we wished to investigate the
      possibility of pooling samples for PCR analysis. Two hundred and sixty-eight
      consecutive female patients attending two gynecology clinics in Copenhagen,
      Denmark were included in this study. Compared to the number of samples regarded
      as true positives, PCR had a sensitivity of 100% (18/18) and EIA a sensitivity of
      83.3% (15/18). The specificity of the PCR analysis was 99.2% (248/250) compared
      to 100% (250/250) for the EIA. By pooling patient samples (five patient samples
      in each pooled sample), a 39% reduction in reagent costs was obtained without
      affecting the sensitivity. In conclusion, the implementation of a standardized
      commercially available C. trachomatis PCR kit leads to a marked increase in
      analytical sensitivity compared to EIA without affecting the specificity. When
      pooled samples were analyzed, the cost per patient sample was reduced, but
      further large-scale studies are needed to rule out the possibility of a reduced
      sensitivity due to the dilution of individual patient samples.

PMID- 7826612
TI  - Structure of the bovine follicle-stimulating hormone receptor complementary DNA
      and expression in bovine tissues.
AB  - We report the complementary DNA structure obtained by reverse transcription and
      polymerase chain reaction amplification encoding the complete amino acid sequence
      for the bovine follicle-stimulating hormone receptor (bFSHr). The deduced amino
      acid sequence for the cDNA revealed a mature polypeptide consisting of 678 amino
      acids (theoretical weight of 76.4 kDa) and a 17 amino acid putative leading
      signal peptide. The receptor consists of a large NH2-terminal extracellular
      membrane domain of 349 aa with 3 potential N-linked glycosylation sites, a
      transmembrane domain (264 aa) consisting of 7 putative membrane spanning
      segments, and an intracytoplasmic COOH-terminal domain (65 aa). Four potential
      phosphorylation sites were found in the transmembrane domain and the COOH
      terminal domain. The amino acid sequence is 97%, 89%, and 88% homologous to the
      ovine, human, and rat FSHr respectively, with complete conservation of the 22
      cysteine residues in the whole protein and the 3 N-linked glycosylation sites on
      the extracellular membrane domain. Northern blot analysis of total mRNA in bovine
      tissues revealed a major mRNA transcript of 2.55 kb for the bFSHr in the ovary
      without corpus luteum, and in the testis. No expression was found in other
      tissues analyzed. Total RNA from bovine granulosa cells collected from pregnant
      mare serum gonadotropin (PMSG)-treated prepubertal heifers showed 2 major mRNA
      transcripts of 6.8 and 2.55 kb, and 3 minor transcripts of 3.8, 3.3, and 1.6 kb.
      Bovine granulosa cells cultured with porcine FSH (0, 2, 10 ng/ml) for 4 days
      showed a decrease in the steady state level of the FSHr mRNA.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7826614
TI  - Relationship between morphology and chromosomal constitution in human
      preimplantation embryo.
AB  - In in vitro fertilization (IVF) procedures, morphologic embryo grading is the
      sole criteria for selection of embryos transferable in utero. Cytogenetic
      analysis of preimplantation embryos was performed to investigate the relationship
      between chromosomal status and morphologic quality of preimplantation eggs.
      Aneuploidy was the most frequently observed abnormality. In addition, various
      types of aberrations such as polyploidy, haploidy, mosaicism, and fragmentation
      were also found. Our results, pooled with data drawn from previous reports,
      demonstrated the prognostic value of the embryo grading system as a means for
      eliminating chromosomally abnormal embryos. In contrast, data suggested that some
      aspects of the IVF process might be responsible for the occurrence of these
      abnormalities.

PMID- 7826613
TI  - Onset of paternal gene activation in early mouse embryos fertilized with
      transgenic mouse sperm.
AB  - We investigated the onset of paternal gene expression in the early mouse embryo.
      We obtained transgenic mouse embryos by fertilizing BD (C57BL/6N x DBA) F1 hybrid
      female oocytes in vitro, with sperm from homozygous transgenic males carrying
      integrated chicken beta-actin promoter-driven firefly luciferase cDNA. We then
      examined the RNA and protein synthesis of the luciferase gene in embryos from the
      1- to 2-cell stage. RNA transcripts of the luciferase gene were first detected in
      the 1-cell stage embryos as early as 13 hr postinsemination, just prior to
      elongation. By photon-count imaging, functional luciferase was identified at the
      2-cell stage 23 hr postinsemination. These findings indicate that the paternal
      endogenous gene is already transcribed in the late 1-cell embryos, although
      paternally derived protein is not synthesized until the 2-cell stage. Therefore,
      these results suggest that the embryonic gene is activated as early as the late 1
      cell stage.

PMID- 7826615
TI  - Transfer of nuclei from 8-cell stage mouse embryos following use of nocodazole to
      control the cell cycle.
AB  - Mouse 2-, 4-, 8-, and 16-cell embryos were exposed to nocodazole in M16 culture
      medium. The effect of different concentrations and exposure times on the
      efficiency of cell cycle synchronization and the development of the treated
      embryos after release from the drug was determined. The minimum effective
      concentration (> 95% of arrested nuclei) for 4-, 8-, and 16-cell embryos was 5
      microM nocodazole. The effect upon subsequent development of mouse embryos
      depended upon both the stage of development of the embryo at treatment (P <
      0.001) and the length of exposure to nocodazole (P < 0.001). Exposure to any
      concentration of nocodazole within the range 2.5-10 microM for 12 hr caused a
      reduction in the proportion of embryos that formed blastocysts. As the period of
      exposure to 5 microM nocodazole increased from 12 to 24 hr, the proportion of
      embryos developing to the blastocyst stage decreased. The lower proportion of
      embryos developing to the blastocyst stage and to term (P < 0.01) suggests that
      the more advanced stages were more susceptible to damage as a result of exposure
      to nocodazole. The rate of development of 4-cell embryos to blastocysts was not
      affected when an exposure time of 9 hr was used. Together these results show that
      it is possible to use nocodazole to arrest mouse embryonic cells in mitosis but
      that it is not appropriate to culture the embryos in the presence of this drug
      for prolonged periods. Individual blastomeres completed mitosis at 60-90 min and
      started DNA synthesis at 120-150 min after release from nocodazole.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7826616
TI  - Production of germline chimeric chickens, with high transmission rate of donor
      derived gametes, produced by transfer of primordial germ cells.
AB  - Germline chimeric chickens were produced by transfer of primordial germ cells
      from White Leghorn to Barred Plymouth Rock, and vice versa. Blood was collected
      from stage 13-15 embryos and primordial germ cells were concentrated by Ficoll
      density gradient centrifugation. Approximately 200 primordial germ cells were
      injected into the bloodstream through the dorsal aorta of stage 14-15 recipient
      embryos from which blood had been drawn via the dorsal aorta prior to the
      injection. Intact embryos were also prepared as recipients for White Leghorns
      only. The manipulated embryos were cultured in recipient eggshells until
      hatching. Germline chimerism of the chickens reaching maturity was examined by
      mating them with Barred Plymouth Rocks and donor-derived offspring were
      identified based on their feather color. The efficiency of production of germline
      chimeras was 95% (19/20). When primordial germ cells were transferred from White
      Leghorn to Barred Plymouth Rock, the average frequency of donor-derived offspring
      was 81% for three male chimeras (96% for one female chimera), and it was
      approximately 3.5 times higher for transfer in the opposite direction (23% for 6
      male chimeras). Removing blood from recipient embryos prior to primordial germ
      cell injection enhanced the frequency of donor-derived offspring by 10% in
      resulting male chimeras. Male chimeras produced donor-derived offspring more
      frequently (approximately 3.8 times) than female chimeras. Increases, decreases,
      or no changes were observed in the frequency of donor-derived offspring from the
      germline chimeras with increasing age.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7826617
TI  - Follicular wall maintains meiotic arrest in bovine oocytes cultured in vitro.
AB  - Cumulus oocyte complexes (COCs) were cocultured with parts of the follicular
      wall. Coculture conditions were such that the COCs were 1) in continuous contact
      with the follicular wall (FWC), 2) separated from the follicular wall at
      collection but in contact with it during culture (FWR), and 3) separated from the
      follicular wall, but cultured in its vicinity (FWNR). Oocytes cultured for 24 hr
      under FWC conditions maintained the germinal vesicle stage. Under FWR conditions
      the germinal vesicle stage was not maintained, but an arrest at metaphase I of
      meiosis occurred in most of the oocytes. When COCs were cultured in the vicinity
      of the follicular wall (FWNR), meiosis was resumed and similar numbers of oocytes
      progressed to metaphase II of meiosis as compared to cultures of COCs without
      coculture with parts of the follicular wall. When COCs were isolated from the
      follicular wall after 24 hr of culture and additionally cultured for another 24
      hr, the oocytes showed the same capability of resuming meiosis as fresh, isolated
      cumulus oocyte complexes. It is concluded that maintenance of contact with the
      follicular wall is necessary to maintain meiotic arrest. When COCs restore a
      physical contact with the follicular wall during culture, an arrest at metaphase
      I occurs.

PMID- 7826618
TI  - Formation of the vitelline envelope precedes the active uptake of vitellogenin
      during oocyte development in the rainbow trout, Oncorhynchus mykiss.
AB  - In order to study the initial formation of the vitelline envelope and the
      appearance of vitellogenin in oocytes of rainbow trout, females were sampled
      monthly from 19 to 5 mo before ovulation. Immunohistochemistry revealed that the
      formation of the vitelline envelope starts when the oocytes reach a diameter of
      about 450 microns. Oocytes of this size were first found in females sampled a
      year before ovulation at the time when plasma levels of estradiol-17 beta
      increased from 0.2 to 0.6 ng/ml. An antiserum directed against vitellogenin
      crossreacted with small vesicles (around 2 microns) present just inside the
      oolemma, when the oocytes reached a diameter of 600 microns. This was interpreted
      as an active uptake of vitellogenin. Oocytes of this size were first found in
      females sampled 9 mo before ovulation at the time when estradiol-17 beta levels
      increased from 0.6 to 1.0 ng/ml and the gonadal somatic index was doubled.
      Oocytes with a diameter of 600 microns had an immunoreactive vitelline envelope
      with a thickness of about 3 microns. It is apparent that the initial formation of
      the vitelline envelope starts before the active uptake of vitellogenin and that
      the low previtellogenic plasma levels of estradiol-17 beta observed in females
      are of physiological significance.

PMID- 7826619
TI  - Modulation of gamete and embryonic microenvironments by oviduct glycoproteins.
AB  - Studies on protein molecules in oviduct luminal fluid are viewed historically,
      and then in terms of more recent studies on a possible involvement of unique
      glycoproteins in embryonic development. As a caution, however, it is noted that
      incorporation of such molecules into the vitellus may be nonspecific. The
      question is raised as to whether oviduct glycoproteins could be acting primarily
      in a physical sense to stabilize differing chemical environments along the
      oviduct. Equally or more importantly, glycoproteins might be acting as carrier
      molecules to present cations and metabolic substrates at appropriate
      concentrations to the vitelline membrane. This latter possibility is examined in
      some detail and could be tested by manipulating the composition of the
      perivitelline fluid. Glycoproteins may also be critically involved in regulating
      the physiological competence of spermatozoa in the pre- and peri-ovulatory
      oviduct, in maintaining a coordinated pattern of cilial beat, and in
      immunosuppressive functions within the oviduct, not least in those associated
      with the masking of paternal antigens on both spermatozoa and embryos.

PMID- 7826620
TI  - Introduction: genes and development symposium: the era of transcription factors
      and gene knockouts.

PMID- 7826621
TI  - The biochemical role of SRY in sex determination.
AB  - The human sex-determining gene on the Y chromosome, termed SRY, has recently been
      isolated by positional cloning; compelling evidence now exists equating SRY with
      the testis-determining factor, TDF. The SRY gene product is an HMG box protein
      whose DNA-binding activity is vital for testis formation as sex-reversed patients
      with SRY mutations lack this activity in vitro. The in vivo DNA target for SRY,
      however, remains elusive. Here, we show, by gel retardation analysis, that SRY
      recognises specific DNA sequences and that such sequences exist upstream of the
      AMH promoter, a potential downstream target for SRY. We also describe the DNA
      bending and cruciform DNA-binding functions of SRY and propose a model for the
      potential action of SRY in the "HMG-1-rich" mammalian nucleus.

PMID- 7826622
TI  - Pdha-2: a model for studying transcriptional regulation in early spermatocytes.
AB  - Precise temporal and tissue-specific expression of genes during spermatocyte
      differentiation is crucial for the formation of functional spermatozoa. However,
      the mechanisms that regulate gene expression during spermatogenesis are poorly
      understood. One testis-specific gene, Pdha-2, is beginning to emerge as a
      potentially important model for the study of these events. This review focuses on
      our current understanding of the expression and regulation of Pdha-2 during
      spermatogenesis.

PMID- 7826623
TI  - T-cell functional regions of the human IL-3 proximal promoter.
AB  - The human interleukin-3 (IL-3) gene is expressed almost exclusively in activated
      T cells. Its expression is regulated at both the transcriptional and post
      transcriptional level. We have previously shown that treatment of Jurkat T cells
      with phytohemaglutinin (PHA) and the phorbol ester, PMA, activated transcription
      initiation from the IL-3 gene. To define the regions of the gene required for
      transcription activation, we generated a series of reporter constructs containing
      different regions of the IL-3 gene 5' and 3' flanking sequences. Both positive
      and negative regulatory elements were identified in the proximal 5' flanking
      region of the IL-3 gene. The promoter region between -173 and -60 contained the
      strongest activating elements. The transcription factor AP-1 could bind to this
      positive activator region of the promoter. We also examined the function of the
      IL-3 CK-1/CK-2 elements that are present in many cytokine genes and found that
      they acted as a repressor of basal level expression when cloned upstream of a
      heterologous promoter but were also inducible by PMA/PHA.

PMID- 7826624
TI  - Regulation of gene expression by transcription factors Ets-1 and Ets-2.
AB  - The ETS family of transcription factors have a DNA-binding domain in common that
      binds a core GGA(A/T) DNA sequence. A large number of proteins have now been
      identified that contain an ETS DNA-binding domain (see review by Wasylyk et al.,
      1993). Ets-1 was first described as the cellular homolog of v-ets. which is
      translated as a 135-kDa gag-myb-ets fusion protein from the replication-deficient
      retrovirus E26 in chickens. Ets-2 was subsequently described as a closely related
      protein that contains the highly conserved ETS DNA-binding domain. This paper
      considers the manner by which the two closely related genes, Ets-1 and Ets-2,
      apparently play distinct roles in embryo development and in the immune system of
      adult mice. Although both Ets-1 and Ets-2 transform fibroblasts (Seth et al.,
      1989), the temporal and tissue-specific expression patterns suggest that these
      two proteins play distinct biological roles and consequently transactivate
      different downstream cellular target genes.

PMID- 7826625
TI  - Basal components of the transcription apparatus (RNA polymerase II, TATA-binding
      protein) contain activation domains: is the repetitive C-terminal domain (CTD) of
      RNA polymerase II a "portable enhancer domain"?
AB  - Regions rich in serine, threonine, and proline residues can be found in
      transcriptional activation domains, as well as in the N-terminal parts of
      mammalian TATA-binding proteins, where they are interrupted by polyglutamine
      stretches. Likewise, the C-terminal domain of the largest subunit of RNA
      polymerase II contains multiple repeats of the consensus heptapeptide sequence
      YSPTSPS. To test directly for possible activation functions, we fused the GAL4
      DNA-binding domain to the N-terminal domain of human TBP or subdomains of it, and
      to the C-terminal domain (CTD) of mouse RNA polymerase II or synthetic polymers
      of a CTD consensus repeat. We found that these chimeric proteins were able to
      activate transcription when bound to a GAL4 site in front of the TATA box, a
      function characteristic of transcription factors. However, while subdomains of
      TBP functioned only from a position close to the TATA box ("promoter" position),
      multiple repeats of the CTD consensus sequence were also able to mediate
      transcriptional activation from a remote ("enhancer") position. Our findings
      suggest that a region of TBP that is unique to mammals functionally cooperates
      with "proximal" activation domains of promoter-bound transcription factors. They
      also imply that the C-terminal domain of RNA polymerase II includes a function
      that is otherwise confined to remote activation domains of enhancer-bound
      transcription factors. We suggest that the CTD of RNA polymerase II contains a
      "portable" remote activation domain that may also facilitate chromatin opening
      within the transcription unit.

PMID- 7826626
TI  - Leukaemia inhibitory factor and the regulation of pre-implantation development of
      the mammalian embryo.
AB  - This paper reviews the evidence that certain growth factors, particularly
      leukaemia inhibitory factor (LIF), play a crucial role in regulating the
      development of the pre-implantation mammalian embryo. LIF was originally
      implicated in regulating the early development of the mouse embryo because it
      inhibited the differentiation of embryonic stem (ES) cells, pluripotential cells
      derived from the inner cell mass of the blastocyst. Subsequent studies on its
      role in vivo revealed, surprisingly, that it is essential for the growth rather
      than the differentiation of the blastocyst. In vivo, overtly normal blastocysts
      can be produced in a LIF-deficient environment that are capable of forming viable
      fertile adults. However, in the absence of LIF, they fail to implant and enter
      into a state resembling that exhibited by blastocysts undergoing delayed
      implantation, which is characterized by a cessation of cell proliferation. This
      failure to implant occurs because the principle sites of LIF production are the
      endometrial glands of the uterus. These synthesize and secrete LIF at
      implantation, with LIF synthesis essential for implantation. Preliminary evidence
      indicates that LIF synthesis is required both by the uterus for it to undergo
      decidualization and by the blastocyst for implantation. These data indicate that
      the maternal environment plays a crucial role in the development and growth of
      the pre-implantation embryo, by supplying factors that regulate these processes
      in the embryo.

PMID- 7826627
TI  - Transforming growth factor-beta 1 in reproduction and development.
AB  - Expression patterns of TGF-beta s during embryogenesis and in adult reproductive
      organs, as well as the activities of these molecules in in vitro assays of
      biological processes relating to reproduction and development, have suggested
      that TGF-beta s may play a role in both reproductive function and embryonic
      development. To investigate the function of TGF-beta 1 in vivo, the murine TGF
      beta 1 gene was disrupted by gene targeting, and animals that lacked TGF-beta 1
      activity were generated. Homozygous mutant animals were obtained which exhibited
      a multifocal inflammatory disease. However, the observed numbers of homozygous
      mutant offspring were less than expected, suggesting the occurrence of some type
      of prenatal lethality. This paper reviews the proposed role of the TGF-beta s in
      reproductive and developmental processes and discusses observations obtained from
      the TGF-beta 1 gene-targeting experiments as they relate to these processes.

PMID- 7826628
TI  - Maggot's hair and bug's eye: role of cell interactions and intrinsic factors in
      cell fate specification.

PMID- 7826629
TI  - Immediate differentiation of ganglion cells following mitosis in the developing
      retina.
AB  - The aim of this study is to gain insight into the time during the life history of
      a retinal neuron that it becomes committed to a particular phenotype. At this
      point, it is not possible to identify the time of commitment, but the time that
      differentiation begins can be identified. Bromodeoxyuridine labeling coupled with
      immunohistochemistry with a ganglion cell-specific antibody was used to fix the
      time of the beginning of ganglion cell differentiation relative to the time of
      mitosis in the developing chick retina. It was found that ganglion cells can
      begin to differentiate in less than 15 min after the end of mitosis. This
      suggests that the retinal ganglion cell fate may be determined before or during
      mitosis.

PMID- 7826630
TI  - Schwann cell processes guide regeneration of peripheral axons.
AB  - Terminal Schwann cells overlying the neuromuscular junction sprout elaborate
      processes upon muscle denervation. We show here that motor axons use these
      processes as guides/substrates during regeneration; in so doing, they escape the
      confines of endplates and grow between endplates to generate polyneuronal
      innervation. We also show that Schwann cells in the nerve provide similar
      guidance. Axons extend from the cut end of a nerve in association with Schwann
      cell processes and appear to navigate along them. The processes extend from
      axotomized nerves at the same rate and in the same manner as they do from axon
      containing nerves. The rate of process extension limits the rate at which axons
      regenerate. Thus, Schwann cell processes lead and guide peripheral regeneration.

PMID- 7826631
TI  - Nerve sprouting in muscle is induced and guided by processes extended by Schwann
      cells.
AB  - Partial denervation or paralysis with botulinum toxin, manipulations that induce
      sprouting of nerve terminals in muscle, also induced terminal Schwann cells to
      extend processes. These processes were associated with every nerve sprout and in
      some cases were longer than the sprouts that appeared to be growing along them.
      Following partial denervation, more than 70% of the nerve sprouts that grew to
      innervate nearby denervated endplates were associated with Schwann cell processes
      that had extended from the denervated endplates, i.e., in the direction opposite
      to nerve growth. Implantation of Schwann cells into an innervated muscle induced
      sprouting upon contact of an axon or nerve terminal by Schwann cell processes.
      These observations show that Schwann cells induce and guide axonal sprouting in
      muscle.

PMID- 7826632
TI  - Late-migrating neuroepithelial cells from the spinal cord differentiate into
      sensory ganglion cells and melanocytes.
AB  - During embryonic development, neural crest cells give rise to many structures in
      peripheral tissues. Other neural tube cells are thought to contribute only to
      structures within the CNS. In contrast to this idea, we report a second wave of
      migration of cells away from the spinal cord occurring after the emigration of
      crest cells is complete. Neuroepithelial cells from spinal cords in E5 chicken
      embryos migrate into the periphery and differentiate into neurons and satellite
      cells within sensory ganglia and into melanocytes in skin and feathers. These
      results show that some cell types previously considered to be the descendants
      exclusively of neural crest cells are also derived from neuroepithelial cells in
      the spinal cord.

PMID- 7826633
TI  - Innervation and target tissue interactions differentially regulate acetylcholine
      receptor subunit mRNA levels in developing neurons in situ.
AB  - Neurons engage in two distinct types of cell-cell interactions: they receive
      innervation and establish synapses on target tissues. Regulatory events that
      influence synapse formation and function on developing neurons are largely
      undefined. We show here that nicotinic acetylcholine receptor (AChR) subunit
      transcript levels are differentially regulated by innervation and target tissue
      interactions in developing chick ciliary ganglion neurons in situ. Using ganglia
      that have developed in the absence of pre- or postganglionic tissues and
      quantitative RT-PCR, we demonstrate that alpha 3 and beta 4 transcript levels are
      increased by innervation and target tissue interactions. In contrast, alpha 5
      transcript levels are increased by innervation, but target tissues have little
      effect. Whole-cell ACh-induced currents, used to estimate the number of
      functional AChRs, change in correlation with alpha 3 and beta 4, but not alpha 5,
      transcript levels. A model is proposed in which the changes in AChR subunit
      expression regulate levels of synaptic activity, which is a critical determinant
      of synapse stabilization and elimination, and neuronal cell death.

PMID- 7826634
TI  - Mutation of an arginine residue in the human glycine receptor transforms beta
      alanine and taurine from agonists into competitive antagonists.
AB  - Agonist binding to the inhibitory glycine receptor (GlyR) initiates the opening
      of a chloride-selective channel that modulates the neuronal membrane potential.
      Point mutations of the GlyR, substituting Arg-271 with either Leu or Gln, have
      been shown to underlie the inherited neurological disorder startle disease
      (hyperekplexia). We show that these substitutions result in the redistribution of
      GlyR single-channel conductances to lower conductance levels. Additionally, the
      binding of the glycinergic agonists beta-alanine and taurine to mutated GlyRs
      does not initiate a chloride current, but instead competitively antagonizes
      currents activated by glycine. These findings are consistent with mutations of
      Arg-271 resulting in the uncoupling of the agonist binding process from the
      channel activation mechanism of the receptor.

PMID- 7826635
TI  - Selective antagonism of AMPA receptors unmasks kainate receptor-mediated
      responses in hippocampal neurons.
AB  - Although both protein and mRNAs for kainate receptor subunits are abundant in
      several brain regions, the responsiveness of AMPA receptors to kainate has made
      it difficult to demonstrate the presence of functional kainate-type receptors in
      native cells. Recently, however, we have shown that many hippocampal neurons in
      culture express glutamate receptors of the kainate type. The large
      nondesensitizing response that kainate induces at AMPA receptors precludes
      detection and analysis of smaller, rapidly desensitizing currents induced by
      kainate at kainate receptors. Consequently, the functional significance of these
      strongly desensitizing glutamate receptors remains enigmatic. We report here that
      the family of new noncompetitive antagonists of AMPA receptors (GYKI 52466 and
      53655) minimally affects kainate-induced responses at kainate receptors while
      completely blocking AMPA receptor-mediated currents, making it possible to
      separate the responses mediated by each receptor. These compounds will allow
      determination of the role played by kainate receptors in synaptic transmission
      and plasticity in the mammalian brain, as well as evaluation of their involvement
      in neurotoxicity.

PMID- 7826636
TI  - Activity-related calcium dynamics in lamprey motoneurons as revealed by video
      rate confocal microscopy.
AB  - In lamprey spinal cord, intracellular calcium ([Ca2+]i) plays a key role in
      mechanisms regulating neuronal activity in the segmental network for locomotion.
      In this report, measurements of [Ca2+]i with fluo-3 in various regions of
      motoneurons in the intact spinal cord were obtained on a high speed confocal
      microscope following electrical stimulation. Likewise, rhythmic calcium
      fluctuations within dendrites and axons were seen during "fictive swimming" and
      were directly correlated with electrical activity. Antidromic stimulation of
      motoneuron axons induced large calcium transients and revealed spatially
      restricted "hot spots," both of which required external calcium and were blocked
      by nickel, but not by known calcium channel antagonists. These results suggest
      that lamprey spinal cord axons may possess a pharmacologically novel class of
      calcium channel.

PMID- 7826637
TI  - Transmitter-mediated inhibition of N-type calcium channels in sensory neurons
      involves multiple GTP-binding proteins and subunits.
AB  - The modulation of voltage-activated Ca2+ channels by neurotransmitters and
      peptides is very likely a primary means of regulating Ca(2+)-dependent
      physiological functions such as neurosecretion, muscle contraction, and membrane
      excitability. In neurons, N-type Ca2+ channels (defined as omega-conotoxin GVIA
      sensitive) are one prominent target for transmitter-mediated inhibition. This
      inhibition is widely thought to result from a shift in the voltage independence
      of channel gating. Recently, however, voltage-independent inhibition has also
      been described for N channels. As embryonic chick dorsal root ganglion neurons
      express both of these biophysically distinct modulatory pathways, we have
      utilized these cells to test the hypothesis that the voltage-dependent and 
      independent actions of transmitters are mediated by separate biochemical
      pathways. We have confirmed this hypothesis by demonstrating that the two
      modulatory mechanisms activated by a single transmitter involve not only
      different classes of G protein but also different G protein subunits.

PMID- 7826638
TI  - A novel protein encoded by the InaD gene regulates recovery of visual
      transduction in Drosophila.
AB  - InaDp215 is a point mutation that affects photoreceptor function in Drosophila.
      To understand the molecular basis of the defect, we isolated the InaD gene and
      found it encodes a photoreceptor-specific polypeptide of 674 residues. Within its
      sequence are two repeats that share remarkable homology with a family of
      cytoskeleton-associated proteins that are involved in signal transduction. Patch
      clamp recordings from isolated photoreceptor cells of InaDp215 show a slow
      deactivation of the light-induced current. This defective deactivation of InaD
      appears dependent on calcium influx; removal of extracellular calcium masks its
      abnormal phenotype. Moreover, InaD photoreceptors show increases sensitivity to
      dim light. We propose that InaD is involved in the negative feedback regulation
      of the light-activated signaling cascade in Drosophila photoreceptors.

PMID- 7826639
TI  - Mice devoid of the glial fibrillary acidic protein develop normally and are
      susceptible to scrapie prions.
AB  - Glial fibrillary acidic protein (GFAP) is an intermediate filament protein
      specifically expressed in astrocytes in the CNS. To examine the function of GFAP
      in vivo, the Gfap gene was disrupted by gene targeting in embryonic stem cells.
      Mice homozygous for the mutation were completely devoid of GFAP but exhibited
      normal development and showed no obvious anatomical abnormalities in the CNS.
      When inoculated with infectious scrapie prions, the mutant mice exhibited
      neuropathological changes typical of prion diseases. Infectious prions
      accumulated in brains of the mutant mice to a degree similar to that in control
      littermates. These results suggest that GFAP is not essential for the
      morphogenesis of the CNS or for astrocytic responses against neuronal injury. The
      results argue against the hypothesis that GFAP plays a crucial role in the
      pathogenesis of prion diseases.

PMID- 7826640
TI  - Targeted disruption of Ca(2+)-calmodulin signaling in Drosophila growth cones
      leads to stalls in axon extension and errors in axon guidance.
AB  - Ca(2+)-calmodulin (CaM) function was selectively disrupted in a specific subset
      of growth cones in transgenic Drosophila embryos in which a specific enhancer
      element drives the expression of the kinesin motor domain fused to a CaM
      antagonist peptide (kinesin-antagonist or KA, which blocks CaM binding to target
      proteins) or CaM itself (kinesin-CaM or KC, which acts as a Ca(2+)-binding
      protein). In both KA and KC mutant embryos, specific growth cones exhibit dosage
      dependent stalls in axon extension and errors in axon guidance, including both
      defects in fasciculation and abnormal crossings of the midline. These results
      demonstrate an in vivo function for Ca(2+)-CaM signaling in growth cone extension
      and guidance and suggest that Ca(2+)-CaM may in part regulate specific growth
      cone decisions, including when to defasciculate and whether or not to cross the
      midline.

PMID- 7826641
TI  - A soluble chimeric form of the L1 glycoprotein stimulates neurite outgrowth.
AB  - Cerebellar neurons, cultured on monolayers of 3T3 fibroblasts or on a
      polylysine/extracellular matrix-coated substratum, responded to a soluble
      recombinant L1-Fc chimera by extending longer neurites than controls. The
      response was inhibited by pretreating neurons with antibodies to L1 or antibodies
      to the fibroblast growth factor (FGF) receptor. The response could also be
      inhibited by a range of pharmacological reagents that inhibit various steps in
      the signal transduction cascade which underlie a neurite outgrowth response to
      basic FGF. The response was of a similar magnitude and not additive with that
      induced by L1 expressed in a cellular substrate. These data show that L1 in
      neurons is capable of directing a neurite outgrowth response to a soluble L1-Fc
      chimera, and that neuronal FGF receptor function is required for this response.
      The data also show that the ability of cell adhesion molecules (CAMs) to
      stimulate neurite outgrowth can be dissociated from their ability to function as
      substrate-associated adhesion molecules and point to the potential of using CAM
      Fc chimeras to promote nerve regeneration.

PMID- 7826642
TI  - p493F12 kinase: a novel MAP kinase expressed in a subset of neurons in the human
      nervous system.
AB  - Monoclonal antibody 3F12 identifies a cytoplasmic antigen of 49 kDa in human
      hippocampus and neocortex. The distribution of 3F12 immunoreactive neurons
      closely matches that of Alzheimer's disease (AD) targeted neurons in these areas.
      In some hippocampal neurons of AD patients, this antigen colocalizes with ALZ-50,
      indicating the presence of AD pathology in these neurons. Molecular
      characterization of the 3F12 cDNA revealed it to be a member of the MAP kinase
      family, showing 43% amino acid sequence identity to human extracellular related
      kinase 2 (p42mapk). We have confirmed that p493F12 kinase autophosphorylates both
      threonine and tyrosine residues, as expected for a MAP kinase. The p49 mRNA is
      expressed exclusively in the nervous system. In the brain, the distribution of
      these neurons closely corresponds to 3F12 antigen-bearing neurons. The p493F12
      gene maps to the human chromosome 21q21 region, a region that may be important in
      the pathogenesis of AD and Down's syndrome.

PMID- 7826643
TI  - Neuronal domains in developing neocortex: mechanisms of coactivation.
AB  - The mammalian neocortex consists of columnar circuits, whose development may be
      controlled by patterns of spontaneous activity. Columnar domains of spontaneously
      coactive neurons were previously described using Ca2+ imaging of slices from
      developing rat neocortex. We have now investigated the cellular mechanisms
      responsible for the coactivation of these domains. The activation starts in the
      center of a domain and spreads at speeds of approximately 100 microns/s. Domains
      occur in the presence of tetrodotoxin but are blocked by the gap junction
      blockers halothane and octanol. Simultaneous intracellular and optical recordings
      from dye-coupled cells reveal functional coupling between developing neocortical
      neurons. These data support the hypothesis that a neuronal domain results from
      the spontaneous excitation of one or a few trigger neurons that subsequently
      activate, either electrically or biochemically, the rest of the cells via gap
      junctions.

PMID- 7826644
TI  - Sensory regulation of male mating behavior in Caenorhabditis elegans.
AB  - C. elegans male mating behavior comprises a series of steps: response to contact
      with the hermaphrodite, backing along her body, turning around her head or tail,
      location of the vulva, insertion of the two copulatory spicules into the vulva,
      and sperm transfer. By ablation of male-specific copulatory structures and their
      associated neurons, we have identified sensory structures and neurons that
      participate in each of these steps: the sensory rays mediate response to contact
      and turning; the hook, the postcloacal sensilla, and the spicules mediate vulva
      location; the spicules also mediate spicule insertion and regulate sperm
      transfer. Generally, successful completion of each step places the male in a
      position to receive a cue for the next step in the pathway. However, the high
      degree of sensory regulation allows the male to execute some steps independently.

PMID- 7826645
TI  - Evidence that pioneer olfactory axons regulate telencephalon cell cycle kinetics
      to induce the formation of the olfactory bulb.
AB  - Early olfactory axons follow a specific pathway to reach the developing
      telencephalon. We observed that a subpopulation of these axons, the pioneer
      olfactory axons, penetrate into the ventricular zone of a highly restricted
      region of the telencephalon at E13 and E14. At E15, this same telencephalic
      region evaginates to form the olfactory bulb. To investigate the possibility that
      the pioneer olfactory axons induce the olfactory bulb by influencing precursor
      cell populations, we compared cell cycle kinetics and differentiation in the
      olfactory bulb primordium and the adjacent neocortex using cumulative
      bromdeoxyuridine labeling. The results showed that, 24 hr after the arrival of
      the first pioneer axons, the duration of the cell cycle is prolonged
      significantly in the olfactory bulb primordium. In addition, twice as many cells
      have exited the mitotic cycle in the olfactory bulb primordium versus the
      adjacent cortex. These findings suggest that pioneer olfactory axons play a role
      in the induction of the olfactory bulb by selectively modulating cell cycle
      kinetics in the olfactory bulb primordium. Afferent axons may influence target
      morphogenesis by modulating target precursor cell proliferation in other
      developing neural structures.

PMID- 7826646
TI  - Evaluating intraoperative radiation therapy (IORT) and external beam radiation
      therapy (EBRT) in non-small cell lung cancer (NSCLC). Five years experience.
AB  - A pilot study on intraoperative radiation therapy (IORT) combined with external
      beam radiation therapy (EBRT) in nonresectable non-small cell lung cancer (NSCLC)
      was performed in 31 patients (mean age: 66.2 years, range: 51-80; 10 anatomically
      and functionally, 21 functionally, nonresectable; 20 squamous-cell, 11
      adenocarcinoma). The tumor was exposed by lateral thoracotomy and a staging lymph
      node dissection was performed (final staging 7 T1, 16 T2, 8 T3; 11 nodal
      positive). Ten to 20 Gy IORT (energy: 7-20 MeV electrons) were delivered to the
      tumor. Unilateral continuous positive airway pressure ventilation of the diseased
      lung was used to reduce the amount of healthy lung tissue in the IORT port and to
      minimize the ventilatory movement. Secondary collimation and direct shielding of
      radio-sensitive structures within the IORT port by aluminium sheets were used to
      further reduce collateral damage. Four weeks after IORT, 46 Gy EBRT (2 Gy/day 5
      times a week; 8-23 MeV photons) were administered to the mediastinum and to the
      tumor-bearing area on an outpatient basis. In nodal positive cases the
      mediastinal dose was increased to 56 Gy. Twenty-three patients were evaluable. In
      13 complete, in 8 partial (50-97% regression) and in 2 minor response has been
      achieved. Five patients experienced a recurrence (local only: 2; local and
      distant: 1; distant only: 2). Twelve patients died of underlying cardio
      respiratory disorders within 6 to 25 months after IORT; 7 died of cancer. The
      overall 5-year survival rate including the incidental deaths is 14.7%. The
      recurrence-free survival rate is 53.2%.

PMID- 7826647
TI  - Effect of type of resection on plasma granulocyte elastase levels following
      surgery for non-small cell lung carcinoma.
AB  - The lung is the primary focus of complications associated with adult respiratory
      distress syndrome (ARDS) and increased activation of granulocytes has been
      implicated in the genesis of ARDS. In the present study, plasma granulocyte
      elastase levels were measured in 24 patients undergoing lung resection for non
      small cell lung carcinoma. Pre-, peri- and post-operative assessments of plasma
      elastase levels were made of patients who underwent a partial resection
      (lobectomy, n = 13) and patients who underwent a complete lung resection
      (pneumonectomy, n = 11). Preoperatively, values were similar for both patient
      cohorts and did not differ from those of normal volunteers. However, immediately
      (1 h) post-operation, elastase levels in patients who had undergone pneumonectomy
      were significantly elevated (300% of baseline value, P < 0.005), whereas levels
      were unchanged in lobectomy patients. On the 1st post-operative day (POD),
      elastase levels had returned to normal in pneumonectomy patients, whilst
      lobectomy patients now exhibited increased plasma elastase levels which remained
      marginally increased until the time of discharge (P < 0.05). The determinants of
      granulocyte activation following lung resection remain to be elucidated but may
      potentially relate to ischemic reperfusion in patients undergoing lobectomy, or
      alternatively may simply reflect the extent of manipulation, compression and
      contusion of lung tissue.

PMID- 7826648
TI  - Early experience of double-lung transplantation with bronchial artery
      revascularization using mammary artery.
AB  - En-bloc double-lung transplantation with tracheal and bronchial revascularization
      using the left internal mammary artery has been performed in 14 Danish patients.
      Primary healing of the tracheal anastomosis was observed in 12 patients, in 10 of
      whom a successful revascularization has been verified by angiography. Two
      patients have been operated recently and not yet examined by angiography. Mucosal
      necrosis and subsequent development of bronchial stenosis had to be treated by
      left-sided pneumonectomy in two patients with failed revascularization. All
      patients were early survivors (1-14 months). We conclude that bronchial
      revascularization with the internal mammary artery is possible with an acceptable
      success rate and is associated with primary healing of the tracheal anastomosis.
      The impact on long-term results remains to be seen.

PMID- 7826649
TI  - Bi-ventricular function assessed intraoperatively before and after anatomical
      correction of transposition of the great arteries.
AB  - After anatomical correction of transposition of the great arteries (TGA), the
      left ventricle (LV) is forced to develop systemic pressures without having had
      time for adaptation. Thus, one might expect dilatation of the LV at least in the
      very early intraoperative period following the operation. In nine patients with
      TGA aged 8-24 days (median 9.5 days) which were selected for arterial switch
      operation (ASO), Dacron-patch mounted thin piezoceramic transducers were attached
      intraoperatively by fibrin glue to opposite epicardial surfaces of the right (RV)
      and/or LV for continuous assessment of external minor diameters (RVD, LVD;
      sonomicrometry) before and after correction. Right and left ventricular pressures
      (RVP, LVP) were measured simultaneously and pressure-diameter loops were
      generated. Right and left ventricular power indices (RVPi, LVPi: = HRxVPxVsD) was
      calculated from heart rate, ventricular pressures, and systolic shortening of the
      respective ventricular diameter (RVsD, LVsD). Data obtained during circulatory
      steady-state immediately before extra-corporeal circulation (ECC) and up to 45
      min after ECC were compared. By avoiding volume overload (CVP < or = 10 mmHg) at
      weaning off ECC and by lowering the systemic vascular resistance and, thus, LV
      afterload (approximately 8 micrograms.kg-1 min-1 dobutamine), the LV developed
      systemic pressure (70 +/- 7 vs. 41 +/- 4 mmHg) at unchanged diastolic LV end
      diastolic pressure (LVedP) (10 +/- 3 mmHg). Left ventricular power index
      increased by 45 +/- 25%, although the extent of systolic shortening of LVD was
      reduced by 20 +/- 10%. Simultaneously, the RV was effectively unloaded (RVedP: 8
      +/- 3 vs 11 +/- 6 mmHg; RVP: 39 +/- 7 vs 53 +/- 9 mmHg; RVPi: -42 +/-
      27%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7826650
TI  - Successful extracorporeal circulatory support after aortic reimplantation of
      anomalous left coronary artery.
AB  - The development of severe heart failure is the main cause of postoperative
      mortality after the surgical treatment of anomalous origin of the left coronary
      artery from the pulmonary artery (ALCAPA). Two patients with ALCAPA who developed
      low cardiac output and could not be weaned from cardiopulmonary bypass (CPB)
      after aortic reimplantation of the anomalous left coronary artery were
      successfully treated with a centrifugal left ventricular assist device (LVAD) and
      extracorporeal membrane oxygenation (ECMO). The circulation of a 10-month-old
      infant with severe left ventricular dysfunction was supported 192 h
      postoperatively with a LVAD and a 9-year-old boy with severe right ventricular
      failure received ECMO support for 99 h following surgery. Both patients survived
      and, 4 and 9 months after surgery, are asymptomatic and have normal ventricular
      function. If CPB (up to 3 h) is not effective in improving ventricular function
      after surgery for ALCAPA, ECMO or LVAD must be used since myocardial recovery in
      these patients can occur only after prolonged extracorporeal circulatory support.

PMID- 7826651
TI  - Mechanical circulatory support in children.
AB  - Nine children (aged 1.2-15 years) have been treated with mechanical circulatory
      support devices at our institution. Indications for treatment were acute cardiac
      allograft rejection (n = 4), postcardiotomy cardiogenic shock (n = 4), and bridge
      to cardiac transplantation (n = 1). Eight patients required left ventricular
      support, and one required biventricular support. A BioMedicus centrifugal pump
      was used in eight patients, and a Hemopump intra-aortic axial flow device was
      used in one patient. In two patients, an intra-aortic balloon pump was in place
      at the time that circulatory support was instituted. Mechanical support time
      ranged from 2 to 139 h, and the average flow index was 2.31 l/min per m2. Three
      patients required hemodialysis during support, and one patient required re
      exploration because of mediastinal hemorrhage. Recovery of native ventricular
      function was assessed by transthoracic or transesophageal echocardiography, and
      weaning from the device was achieved by gradually decreasing pump flow in
      increments of 0.1 to 0.5 l/min. Seven patients were successfully weaned from
      support. Two hospital deaths occurred after circulatory support had been
      discontinued: one patient died of respiratory failure and the other of gram
      negative pneumonia and sepsis. The five surviving patients experienced no
      significant complications, and their hemodynamic indices were normal at the time
      of discharge. At a mean follow-up of 28.8 months, these patients are leading
      active unrestricted lives, with no long-term device-related sequelae. Based on
      this experience, mechanical circulatory support is feasible in children who
      experience profound circulatory failure from a variety of causes.

PMID- 7826652
TI  - A ten-year study of the Ionescu-Shiley low-profile bioprosthetic heart valve.
AB  - Seven hundred and eight adults (age > or = 16 years) with isolated aortic (n =
      433) or mitral (n = 275) Ionescu-Shiley Low-Profile (ISLP) pericardial valves
      were followed at 14 implanting centres in Canada, the United Kingdom, and the
      United States for a mean of 6.7 years, providing 4,729 patient-years of clinical
      data. The operative mortality rate was 3.0% for aortic valve replacement (AVR)
      and 5.5% for mitral valve replacement (MVR) (p = ns). Actuarial patient survival
      following AVR at 5 years was 81.6%, and 62.9% at 10 years; for MVR patients it
      was 78.1% at 5 years and 59.6% at 10 years. The ISLP valve appears to have
      durability comparable to other contemporary bioprosthetic valves. For aortic
      prostheses, the freedom from structural deterioration was 96.5% at 5 years and
      73.7% at 10 years, and 89.7% at 5 years and 62.4% at 10 years for mitral
      prostheses. Structural deterioration was significantly more frequent following
      MVR than after AVR (p < 0.05). Structural deterioration was the principal cause
      for reoperation, but sudden deterioration precluding safe reoperation was not a
      dominant feature of this series. The ISLP valve appeared to engender more thrombo
      embolic events than would be anticipated from earlier studies of pericardial
      bioprostheses, but was indistinguishable from other tissue valves in its
      incidence of other valve-related complications. We conclude that ISLP valves now
      implanted for 7 years or more are entering a phase of increasing structural
      deterioration, indicating the need for regular clinical and echocardiographic
      surveillance, and that long-term anticoagulation should be instituted for
      relatively minimal indications in these patients.

PMID- 7826653
TI  - In vitro immunogenicity of allogeneic cardiac valves.
AB  - The immunogenicity of allogeneic cardiac valves (ACV) has not been previously
      demonstrated in vitro, though valve failure due to tissue degeneration has been
      attributed to adverse immunological reactions. A novel in vitro assay has been
      developed in a Brown Norway (BN; RT1n)-Lewis (RT1; donor-recipient) rat model
      system that demonstrates the immunogenicity of ACVs. A single cell suspension of
      viable cardiac valve conduit (CVC) cells was obtained by collagenase treatment of
      BN rat aortic valve conduits. Brown Norway rat CVC cells (5 x 10(4)) and Lewis
      responder lymphocytes (10(5)) were co-cultured in 96 well plates in RPMI 1640
      plus 2.5% (v/v) non heat-inactivated Lewis rat serum and supplements with
      appropriate controls. Stimulation of responder lymphocytes by CVC cells was
      measured by 3H-thymidine incorporation into DNA. The counts obtained between 96
      192 h of co-culture in the CVC cell/responder lymphocyte reaction were
      significantly higher (P < 0.05) than those of responder cell controls as assessed
      by analysis of variance. These results indicate the presence of potent
      immunostimulatory cells in viable ACVs and the possibility of using a sensitive
      and reproducible in vitro assay to evaluate ACV immunogenicity.

PMID- 7826654
TI  - The safety of intermittent warm blood cardioplegia.
AB  - Continuous warm blood cardioplegia is considered to be an effective method for
      myocardial protection. However, frequently the flow of the cardioplegia needs to
      be interrupted for better visualization. Intermittent warm blood cardioplegia was
      reported to be safe by some investigators. To assess the degree of this safety,
      76 patients who underwent operations for coronary or valvular disease, or both,
      were divided into two groups of 38 patients each. The two groups were well
      matched for age, ejection fraction, number of coronary bypasses and type of
      valvular procedures. Cold blood cardioplegia (CBC) was used intermittently every
      15 min in the first group while the second group received warm blood cardioplegia
      (WBC) intermittently every 15 min. The clamp time range was 50-140 min. There
      were no deaths in either group, four myocardial infarctions occurred, two in each
      group. Low cardiac output occurred in 13 patients of the WBC group and in 7
      patients of the CBC group, electrocardiogram (ECG) global ischemic changes were
      recorded in 14 patients of the WBC group compared to 6 patients of the CBC group.
      Statistically the results indicate that the techniques are comparable if the
      clamp time is less than 90 min. However, after 90 min the development of ECG
      changes and low cardiac output are significantly higher when WBC is used P <
      0.001. Therefore, it is concluded that using the WBC intermittently is as safe as
      CBC when the clamp time is less than 90 min, however extra precautions are needed
      with longer clamp times.

PMID- 7826655
TI  - Indirect myocardial revascularization--an experimental study in the dog.
AB  - It has been shown in previous studies that grafting a free skeletal muscle flap
      onto the heart of the dog produces myocardial revascularization. In order to
      evaluate the functional aspect of these neovessels, an Ameroid constrictor was
      implanted into the LADs (left anterior descending coronary artery) of five dogs.
      At the same time, the free muscle flap was grafted onto the anterior wall of the
      heart. The arterial anastomosis was achieved with the internal mammary artery.
      Venous flow was drained into the right atrium. About 12 months later, the
      regional myocardial blood flow was evaluated adopting the radioactive microsphere
      technique. This was carried out with the LAD occluded by the Ameroid constrictor
      and the circumflex artery (CX) open (control conditions). Then the CX was
      occluded in order to exclude collateral blood flow. Afterwards another occlusion
      of the CX was performed ("preconditioning") to produce maximal opening of the
      anatomical collaterals. It was found that regional myocardial blood flow was
      unchanged in the antero-lateral parts of the hearts despite complete occlusion of
      the coronaries supplying this area. In the parts supplied by the CX, though, flow
      was minimal. "Preconditioning" positively influenced the perfusion of this region
      only in the epicardial parts. Histologically large sinusoid-like blood conductors
      connected the graft and the heart. Thus, grafting a free skeletal muscle flap
      onto the heart in the dog produces functional myocardial revascularization in the
      dog.

PMID- 7826656
TI  - Efficacy of autologous peritoneum as a biological membrane in cardiac surgery.
AB  - The risks for reoperative cardiac surgery are related to the presence of
      intrapericardial adhesions and the possibility of catastrophic injury at repeat
      sternotomy. In an attempt to develop an improved pericardial substitute and
      vascular patch, the feasibility of using autologous peritoneum was evaluated.
      Twelve mongrel dogs were studied. A peritoneal-rectus fascia patch, including the
      overlying posterior rectus sheath was harvested, via a lateral abdominal
      incision, and stored in normal saline. In the first group of six animals, a
      pulmonary artery (PA) window was created and then closed with the peritoneal
      rectus fascia patch. In the second group a secundum atrial septal defect was
      created and then closed with the peritoneal patch on cardiopulmonary bypass
      (CPB). In each animal, the peritoneal-rectus fascia patch was used to permit
      pericardial closure. Autopsies performed at 90 days postoperatively revealed only
      slight intrapericardial adhesion formation and a mild epicardial reaction.
      Histological examination of the peritoneal-rectus fascia patches revealed intact
      morphology with active fibroblasts and smooth muscle cells. Proline 14C
      absorption and autoradiography detected viable cells in the implanted patches.
      These findings suggest that a peritoneal-rectus fascia allograft could be useful
      as a biological membrane, and as a satisfactory pericardial substitute in the
      development of strategies to reduce the risk for reoperative cardiac surgery.

PMID- 7826657
TI  - Unusual left atrial mass following cardiac surgery in an infant.
AB  - An unexpected left atrial mass was found during routine postoperative
      transthoracic echocardiogram in an infant following surgical closure of
      ventricular septal defect. Thrombus could not be excluded. At reoperation it was
      found to be an inverted left atrial appendage. This case demonstrates the
      echocardiographic appearance of an inverted left atrial appendage.

PMID- 7826658
TI  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin-mediated gene expression in the immature rat
      thymus.
AB  - To examine the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on thymic
      gene expression in vitro, freshly isolated rat thymocytes were incubated with 10
      nM TCDD, and reverse transcriptase polymerase chain reaction experiments were
      performed using primers specific for prostaglandin G/H synthase (PGHS) and
      glyceraldehyde 3-phosphate dehydrogenase. TCDD selectively repressed PGHS gene
      expression, with maximal inhibition occurring within 60 min. Gel retardation
      assays demonstrated that dioxin transiently induced binding of the ubiquitous
      transcription factor NF kappa B to its cognate response element at early time
      points. However, TCDD had little ability to induce transformation of the Ah
      receptor to the xenobiotic responsive element in thymic cytosol. These results
      indicate that TCDD exerts changes in thymocyte gene expression prior to inducing
      toxicity.

PMID- 7826659
TI  - Mechanisms of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced disruption of B
      lymphocyte signaling in the mouse: a current perspective.
AB  - TCDD treatment of B cells appears to induce kinase activity (i.e., possibly
      tyrosine kinases) as well as increases in resting intracellular calcium
      concentration, in the absence of any other stimuli. These activities, either
      together or apart, may result in an inappropriate activational response,
      rendering the B cell less responsive to stimulation by antigen or mitogens. TCDD
      appears to selectively inhibit B-cell responses that involve demonstrable calcium
      involvement. The functional defect caused by TCDD is most likely downstream of
      phospholipase C, since the B-cell proliferative response to PMA plus ionomycin is
      strongly inhibited by TCDD. It remains unclear how an elevation of intracellular
      calcium fits in with the described profile of activity for TCDD on B cells.
      Although it seems probable that disrupted calcium homeostasis would result in
      changes in membrane permeability, ionic fluxes are poorly understood in general,
      and in B cells, there is no current evidence that TCDD exposure can induce
      calcium-activated apoptosis. Furthermore, it is not known if increases in
      intracellular calcium are associated with the pattern of tyrosine phosphorylation
      reported for TCDD in B cells. Since changes in calcium have also been observed in
      other tissues, our results support a role for alteration of calcium homeostasis
      as a common mechanism for TCDD toxicity. It appears that for complex biological
      responses to occur, such as proliferation, or the manufacture and secretion of
      proteins, several signal transduction pathways must converge. The ultimate
      outcome of these information inputs likely depends upon the strength of the
      individual stimuli, the integrative capabilities of the combined stimuli, and the
      maturational stage of the cell.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7826660
TI  - Evaluation of possible effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin and other
      congeners on lymphocyte receptors in Callithrix jacchus and man.
AB  - Using fluorescence-labeled monoclonal antibodies and flow cytometry (FACScan
      analysis) we measured surface receptors on peripheral lymphocytes in marmosets
      (Callithrix jacchus) treated with TCDD in the lower nanogram per kilogram range.
      Additionally, some polybrominated congeners were studied as well as a 2,3,7,8
      substituted dioxin containing chlorine and bromine in the same molecule.
      Callithrix was found to be very sensitive to the action of TCDD and the other
      tetrahalogenated congeners; single doses of 10-30 ng/kg body weight reproducibly
      induced a decrease in the percentage and absolute number of 'memory' helper T
      cells [CD4+CD29(bright)] and of B cells (CD20+). Subsequently, according to the
      hypothesis based on the marmoset data, extensive analyses on surface receptors of
      white blood cells were performed in workers with moderately increased body
      burdens of TCDD, and for further hypothesis generation > 60 triple-labeling
      assays were performed with each of the blood samples. No decrease in typical
      surface receptors (CD4+CD45R0+CD45RA-CD29(bright) or CD20+) was found in the
      human adult volunteers studied, but a trend toward an increase was noted. It
      cannot be decided whether this may be a substance-related effect, or results from
      a confounder (possibly age differences between the groups).

PMID- 7826661
TI  - Dioxin-enhanced expression of interleukin-1 beta in human epidermal
      keratinocytes: potential role in the modulation of immune and inflammatory
      responses.
AB  - Human keratinocytes are an important source of cytokines that participate in
      inflammatory and immunological processes of the skin. 2,3,7,8-Tetrachlorodibenzo
      p-dioxin (TCDD) has been shown to enhance the expression of the cytokine,
      interleukin-1 beta (IL-1 beta), in a human keratinocyte cell line. Here we have
      expanded this observation to primary cultures of normal human epidermal
      keratinocytes. Treatment of these cells with TCDD resulted in increased
      expression of IL-1 beta mRNA. Both the magnitude and relative fold increase of
      levels of IL-1 beta mRNA were affected by specific culture conditions. In
      specific analyses of each culture medium supplement, bovine pituitary extract
      (BPE) was shown to exert the greatest effect on both the constitutive and TCDD
      inducible expression of IL-1 beta mRNA, and this effect of BPE was shown to be
      concentration-dependent. These results indicate that, in vitro, enhanced
      expression of IL-1 beta is a response of normal human epidermal keratinocytes to
      TCDD and furthermore, that the intensity of this response may be modulated by
      additional growth factors, including those present in BPE.

PMID- 7826662
TI  - Tumor necrosis factor involvement in the toxicity of TCDD: the role of endotoxin
      in the response.
AB  - We have previously demonstrated that tumor necrosis factor is involved in the
      acute toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), since
      therapies designed to attenuate the effects of tumor necrosis factor resulted in
      reduced mortality and toxicity in mice exposed to an LD75 dose of TCDD. The
      current study addresses whether endotoxin may be a contributing factor in the
      cachexia and mortality resulting from TCDD exposure. Endotoxin-nonresponsive
      C3H/HeJ mice and endotoxin-responsive C57BL/6 mice were treated with 350
      micrograms/kg TCDD and body weight and mortality were recorded. C3H/HeJ mice
      showed no trend in body weight loss (p = 0.554), while C57BL/6 mice demonstrated
      a statistically significant (p < 0.01) linear decline in body weight of -0.23
      g/day, resulting in a net loss of 3.5 g over 15 days preceding mortality.
      Mortality was observed in the C57BL/6 mice beginning on day 16 with 100% of the
      mice dying by the 23rd day while no mortality was observed in C3H/HeJ mice until
      the 24th day of the study with only 22% mortality observed. These data further
      demonstrate that endotoxin is a contributing factor to the cachexia and lethality
      of TCDD.

PMID- 7826663
TI  - Modulation of growth factor expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a widespread environmental
      contaminant, which causes a variety of toxic effects including alterations in
      cell growth and differentiation. In the last years it became increasingly evident
      that growth factors and their corresponding receptors are involved in toxic
      responses of this compound. The interference of TCDD with growth factor
      expression has been studied in several in vitro and in vivo systems. Here, we
      give a short summary of the published data about interactions between TCDD and
      growth factors.

PMID- 7826664
TI  - Immunotoxicity of polychlorinated biphenyls: present status and future
      considerations.
AB  - Polychlorinated biphenyls (PCBs) are widely spread environmental contaminants
      consisting of chemical mixtures containing many of the 209 possible congeners.
      The potential immunomodulatory properties of PCBs have been the subject of
      extensive experimental investigations. The available evidence indicates that the
      immune system is a target for PCBs and is perhaps one of the most sensitive
      indicators for adverse PCB-induced health effects. Recent advances regarding the
      mechanism of PCB-induced immunotoxicity point to their dependency on the presence
      of the aromatic hydrocarbon receptor and their ability to bind to this receptor
      as the venue for their toxicological activity. Their binding affinity depends on
      the degree of chlorination of the biphenyl structure and the position of the
      chlorine atoms. Such advances have contributed significantly to the determination
      of the relative immunotoxic potential of PCB mixtures and to the calculation of
      TEFs for several of the PCB congeners. Such information is critical for
      evaluating the potential risk PCBs pose to human health. To fully exploit the
      potential contribution immunotoxicology can make to risk assessment, it is
      important that the data base on mechanism(s) of PCB-induced immunotoxicity and
      the potential agonistic/antagonistic properties of PCBs be expanded considerably.

PMID- 7826665
TI  - Risk assessment for possible effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD) and related substances on components and functions of the immune system.
AB  - Numerous reports have been published on the effects of 2,3,7,8-tetrachlorodibenzo
      p-dioxin (TCDD) on components and functions of the immune system of animal
      species, almost exclusively of rodents. Many of the data, obtained with very
      different dosing schedules, are conflicting or have not been confirmed. Since the
      overwhelming majority of evaluations were performed with rodents, it is not
      possible to perform a reliable quantitative or even qualitative risk assessment
      for TCDD in man based on immunological data obtained from these experiments and
      to extrapolate them to the situation in humans. In addition to the fact that the
      doses needed to induce measurable effects in the different species studied varies
      from 1- to 10,000-fold, there are intrinsic and general difficulties for
      extrapolations to human beings in the field of immunotoxicology due to the
      influence of different individual risk factors, e.g. smoking and drinking as well
      as the lack of experience and validation in this new field of toxicology. Some
      immunological variables were studied in populations highly exposed to dioxins. In
      comparison to the results obtained from nonhuman primates, no convincing evidence
      for substance-related effects was revealed, however, information on only a few
      immunological components and functions in exposed adults could be assessed so
      far. Except for one group of studied persons all other subjects were generally
      exposed to cocktails of several chemicals, vastly complicating the interpretation
      with respect to one isolated component of these mixtures. Results from studies on
      exposed children are not available yet.

PMID- 7826666
TI  - Dioxins and the immune system. Mechanisms and consequences of interference.

PMID- 7826667
TI  - Ah receptor: a novel ligand-activated transcription factor.
AB  - Two years have passed since the Ah receptor (AhR) and the AhR nuclear
      translocator (Arnt) were revealed to constitute a novel ligand-activated
      transcription factor by molecular biological studies on cloned cDNAs. Many
      interesting properties of the AhR/Arnt system have begun to be elucidated. We
      present here a brief summary of the molecular biology of AhR and Arnt.

PMID- 7826668
TI  - Proliferation inhibition and CD4/CD8 thymocyte subset skewing by in vivo exposure
      of C57BL/6 mice to Ah receptor-binding 3,3',4,4'-tetrachlorobiphenyl.
AB  - 3,3',4,4'-Tetrachlorobiphenyl (TCB) and other Ah receptor-binding xenobiotics
      lead to thymus atrophy and immunosuppression, the former possibly causing the
      latter. In order to better understand the TCB-induced events in the murine
      thymus, we analyzed the effects of TCB on the proliferation capacity and
      maturation kinetics of different thymocyte subsets in 2-week-old C57BL/6 mice
      (i.e. of the Ahb-1 'dioxin-sensitive' genotype). Mice were injected with a single
      dose of TCB, and the development of thymocytes was followed up for 10 days using
      flow cytometric surface marker analysis combined with measurement of DNA content
      by 7-amino-actinomycin D staining. Already 2 days after exposure to TCB, fewer of
      the more immature thymocytes (CD4-CD8-, CD4-CD8+ alpha beta TCR-) were
      proliferating than in thymi from control animals. Eventually this led to a severe
      decrease in thymus cellularity. Moreover, a shift towards the CD4-CD8+ mature
      subpopulation was observed. The effects were reversible, and proliferation and
      CD4/CD8 subset distribution returned to normal levels within the observation
      period. The results are in good agreement with the data obtained previously in
      vitro with fetal thymus organ cultures.

PMID- 7826669
TI  - The intrathymic target cell for the thymotoxic action of 2,3,7,8
      tetrachlorodibenzo-p-dioxin.
AB  - Sublethal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) produces thymic
      atrophy and thymic lymphodepletion in all species investigated. Lymphodepletion
      is first seen in the cortex of the thymus, but also occurs in the medulla at
      later time points. This article surveys in vivo and in vitro studies on TCDD
      induced thymus toxicity. It is concluded that the first intrathymic target cell
      for the action of TCDD is the cortical epithelial cell.

PMID- 7826670
TI  - Alternate immune system targets for TCDD: lymphocyte stem cells and extrathymic T
      cell development.
AB  - We here summarize evidence that thymic atrophy induced by 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) can be mediated, at least in part, by damage
      to extrathymic T-cell precursors in bone marrow and fetal liver. This atrophy
      induction does not involve apoptotic mechanisms in thymocytes affected by the bcl
      2 proto-oncogene. TCDD mediates atrophy induction through its specific receptor
      (the AhR) and not through effects on the estrogen receptor. Both TCDD and
      estradiol induce extrathymic T-cell differentiation in the liver. These
      extrathymic T-cell populations include cells expressing elevated levels of V beta
      T-cell receptors that are normally deleted in thymic development.

PMID- 7826671
TI  - DNA recognition by intercalators and hybrid molecules.
AB  - Experiments are described which probe the role of the 2-amino group of guanine as
      a critical determinant of the recognition of nucleotide sequences in DNA by
      specific ligands. Homologous samples of tyrT DNA substituted with inosine or 2,6
      diaminopurine residues in place of guanosine or adenine respectively yield
      characteristically modified footprinting patterns when challenged with sequence
      selective antibiotics such as echinomycin, actinomycin or netropsin. The capacity
      of small molecules to recognise particular DNA sequences is exploited in the
      'combilexin' strategy to target small molecules to defined sites in DNA. A
      composite molecule containing a distamycin moiety linked to an intercalating
      ellipticine derivative has been synthesised and shown to bind tightly to DNA but
      without much sequence-selectivity. Refinement of this molecule based on
      predictions from molecular modelling has led to the synthesis of a second
      generation derivative bearing an additional positive charge: this new hybrid
      molecule is strongly selective for binding to AT-rich tracts in DNA.

PMID- 7826672
TI  - (+)-CC-1065 as a probe for intrinsic and protein-induced bending of DNA.
AB  - (+)-CC-1065 is a biologically potent DNA-reactive antitumor antibiotic produced
      by Streptomyces zelensis. This antibiotic covalently modifies DNA by alkylation
      of N-3 of adenine in the minor groove. As a structural consequence of covalent
      modification of DNA, the helix axis is bent into the minor groove. The drug
      induced bending of DNA has similarities to intrinsic A-tract bending and the 3'
      adenine of A-tracts shows a unique reactivity to alkylation by (+)-CC-1065. Upon
      covalent modification of A-tracts, the magnitude of bending is increased and the
      helix is stiffened. Using high-field NMR, hydroxyl-radical footprinting and gel
      electrophoresis, the molecular basis for the high reactivity of the bonding
      sequence 5'-AGTTA* (an asterisk indicates the covalent modification site) to (+)
      CC-1065 has been shown to involve the inherent conformational flexibility of this
      sequence. Furthermore, these studies also demonstrate that after alkylation the
      drug-induced bending is focused over the TT region. By analogy with the junction
      bend model for A-tracts, a 'truncated junction bend model' is proposed for this
      structure. Last, the application (+)-CC-1065 entrapped/induced bending of DNA as
      a probe for the Sp1-induced bending of the 21-base-pair repeat and Mu transposase
      bending of the att L3 sequence is described.

PMID- 7826673
TI  - Quantitative footprinting analysis.
AB  - This review outlines the steps for obtaining relative binding constants for drugs
      from footprinting data. After correcting the autoradiographic spot intensities
      for differing amounts of radioactive DNA loaded into the lanes of a sequencing
      gel, footprinting plots, showing individual spot intensities as a function of
      drug concentration, are constructed. The initial relative slopes of footprinting
      plots are proportional to the binding constant of the drug for its DNA site.
      Slopes of plots outside of drug binding sites can be used to identify locations
      of altered DNA structure. It illustrates the power of quantitative footprinting
      analysis by analyzing the binding of the antiviral agent netropsin to a 139-base
      pair restriction fragment in the presence of the antitumor agent actinomycin D.
      While two netropsin binding regions are unaffected by actinomycin D a third
      region experiences enhanced binding in the presence of the antitumor agent.

PMID- 7826674
TI  - Analysing DNA complexes by circular and linear dichroism.
AB  - The application of linear and circular dichroism (LD and CD) in nucleic acid
      research is illustrated by recent results aimed at answering specific structural
      problems in the interaction of DNA with molecules of biological importance. We
      first consider the circumstances under which ligands, such as DAPI (4',6
      diamidino-2-phenylindole), change their preferred binding mode in the minor
      groove to major groove binding or intercalation. As an extension of this problem
      we refer to the switch between groove binding and intercalation of structurally
      similar ligands such as ellipticines and trigonal ruthenium complexes. We also
      explore the use of LD and CD in the determination of the structure of the complex
      formed between the polynucleotide poly(dA) and the novel 'peptide nucleic acid',
      consisting of nucleic acid bases joined by a polyamide homomorphous with the
      deoxyribose-phosphate backbone of DNA. Finally, the structure and interaction of
      the recombination enzyme RecA with DNA is discussed, in particular the influence
      of the presence of intercalators, groove binders or covalent DNA adducts.

PMID- 7826675
TI  - DNA recognition by DNase I.
AB  - Bovine pancreatic DNase I shows a strong preference for double-stranded
      substrates and cleaves DNA with strongly varying cutting rates suggesting that
      the enzyme recognises sequence-dependent structural variations of the DNA double
      helix. The complicated cleavage pattern indicates that several local as well as
      global helix parameters influence the cutting frequency of DNase I at a given
      bond. The high resolution crystal structures of two DNase I-DNA complexes showed
      that the enzyme binds tightly in the minor groove, and to the sugar-phosphate
      backbones of both strands, and thereby induces a widening of the minor groove and
      a bending towards the major groove. In agreement with biochemical data this
      suggests that flexibility and minor groove geometry are major parameters
      determining the cutting rate of DNase I. Experimental observations showing that
      the sequence environment of a dinucleotide step strongly affects its cleavage
      efficiency can be rationalized by the fact that six base pairs are in contact
      with the enzyme. Mutational analysis based on the structural results has
      identified critical residues for DNA binding and cleavage and has lead to a
      proposal for the catalytic mechanism.

PMID- 7826676
TI  - Molecular recognition of DNA structure by proteins that mediate genetic
      recombination.
AB  - The latter half of genetic recombination is mediated by proteins that recognise
      the structure of the four-way DNA junction, and manipulate this structure. In
      solution the four-way junction adopts a stacked X-structure in the presence of
      metal ions. The folding is brought about by the pairwise coaxial stacking of
      helices in a right-handed antiparallel X-shaped structure. The four-way junction
      is cleaved by structure-selective resolving enzymes that have been isolated from
      a wide variety of sources, from eubacteria and their phages through to mammals.
      In addition, another class of proteins accelerate the branch migration of the
      junction. These proteins all appear to be divisible into a component that
      recognises structure and another that carries out a reaction on the junction.
      Thus the ability of structure-selective binding to the four-way DNA junction is a
      key feature of enzymes important in genetic recombination.

PMID- 7826677
TI  - DNA recognition by lexitropsins, minor groove binding agents.
AB  - Consideration is given to alternative approaches to the development of DNA
      sequence selective binding agents because of their potential applications in
      diagnosis and treatment of cancer as well as in molecular biology. The concept of
      lexitropsins, or information-reading molecules, is introduced within the antigene
      strategy as an alternative to, and complementary with, the antisense approach for
      cellular intervention and gene control. The chemical, physical and
      pharmacological factors involved in the design of effective lexitropsins are
      discussed and illustrated with experimental results. Among the factors
      contributing to the molecular recognition processes are: the presence and
      disposition of hydrogen bond accepting and donating groups, ligand shape,
      chirality, stereochemistry, flexibility and charge. For longer ligands, such as
      are required to target unique sequences in biological systems (14-16 base pairs),
      the critical feature is the phasing or spatial correspondence between repeat
      units in the ligand and the receptor. The recently discovered 2:1 lexitropsin-DNA
      binding motif provides a further refinement in molecular recognition in
      permitting discrimination between GC and CG base pairs. The application of these
      factors in the design and synthesis of novel agents which exhibit anticancer,
      antiviral and antiretroviral properties, and inhibition of critical cellular
      enzymes including topoisomerases is discussed. The emerging evidence of a
      relationship between sequence selectivity of the new agents and the biological
      responses they invoked is also described.

PMID- 7826678
TI  - The interaction of intercalators and groove-binding agents with DNA triple
      helical structures: the influence of ligand structure, DNA backbone modifications
      and sequence.
AB  - The effects of ligand structure and properties, DNA backbone modifications and
      DNA sequence on the interaction of a variety of well-known groove-binding agents
      and intercalators with DNA duplexes and triplexes have been evaluated by thermal
      melting experiments and molecular modeling. Both methylphosphonate and
      phosphorothioate substitutions generally destabilize DNA duplexes and triplexes.
      Modified duplexes can be strongly stabilized by both groove-binding agents and
      intercalators whereas triplexes are primarily stabilized by intercalators. Of the
      compounds tested, the intercalators coralyne and quinacrine provide the largest
      stabilization of the triplex dT19.dA19.dT19. Molecular modeling studies suggest
      that the large intercalating ring system of coralyne stacks well with the triplex
      bases whereas the alkylamino side chain of quinacrine fits snugly into the
      remaining space of the major groove of dT19.dA19.dT19 triplex and forms extensive
      van der Waals contacts with the thymine methyl groups that line the groove.
      Converting some of the T.A.T base triples to C+.G.C (e.g. dT19.dA19.dT19 to
      d(T4C+)3T4.d(A4G)3A4.(T4C)3T4) causes very significant decreases in observed Tm
      increases for compounds such as quinacrine and coralyne. Although removal of
      thymine methyl groups and addition of positive charge on substitution of C+.G.C
      for T.A.T should reduce binding of cationic intercalators, the large difference
      observed between the pure AT and the mixed sequence triplexes suggest that they
      may also have differences in structure and properties.

PMID- 7826679
TI  - Design of molecules that specifically recognize and cleave apurinic sites in DNA.
AB  - We have prepared a series of tailor-made molecules that recognize and cleave DNA
      at apurinic sites in vitro. These molecules incorporate in their structure
      different units designed for specific function: an intercalator for DNA binding,
      a nucleic base for abasic site recognition and a linking chain of variable length
      and nature (including amino and/or amido functions). The cleavage efficiency of
      the molecules can be modulated by varying successively the nature of the
      intercalating agent, the nucleic base and the chain. All molecules bind to native
      calf thymus DNA with binding constants ranging from 10(4) to 10(6) M-1. Their
      cleavage activity was determined on plasmid DNA (pBR 322) containing 1.8 AP-sites
      per DNA-molecule. The minimum requirements for cleavage are the presence of the
      three units, the intercalator, the nucleic base and at least one amino function
      in the chain. The most efficient molecules cleave plasmid DNA at nanomolar
      concentrations. Enzymatic experiments on the termini generated after cleavage of
      AP-DNA suggest a strand break induced by a beta-elimination reaction. In order to
      get insight into the mode of action (efficiency, selectivity, interaction), we
      have used synthetic oligonucleotides containing either a true abasic site at a
      determined position to analyse the cleavage parameters of the synthetic molecules
      by HPLC or a chemically stable analog (tetrahydrofuran) of the abasic site for
      high field 1H NMR spectrometry and footprinting experiments. All results are
      consistent with a beta-elimination mechanism in which each constituent of the
      molecule exerts a specific function as indicated in the scheme: DNA targeting,
      abasic site recognition, phosphate binding and beta-elimination
      catalysis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7826680
TI  - Findings of scientific misconduct.

PMID- 7826681
TI  - The clinical implication of theophylline intoxication in the Emergency
      Department.
AB  - We reviewed the clinical manifestations of 53 episodes of theophylline
      intoxication in 50 patients over a one year study period, in order to identify
      the specific features as they presented to the Emergency Department (ED). There
      was a trend to an increase in the serum theophylline concentration with increased
      severity of clinical features, but the difference between the mild and the
      moderate cases was not statistically significant. The most common symptoms and
      signs were gastrointestinal complaints, sinus tachycardia, and atrial
      arrhythmias. Mixed atrial and ventricular arrhythmias, which are rarely mentioned
      as a specific feature of theophylline intoxication, were found in 16% of our
      patients and accounted for 29% of the cardiovascular manifestations. Four
      patients developed rhabdomyolysis, which presumably was secondary to a seizure or
      profound hypokalaemia. Cases of theophylline intoxication presenting to the ED
      had higher serum concentrations of theophylline and tended to have more severe
      toxicity than those patients in the non-ED group. Delayed diagnosis may
      contribute to the severity of the outcome, since severe cases in the ED were
      usually suspected to have developed intoxication at some point later in the stay
      in the ED than at the time of presentation, or after admission to the hospital,
      thus permitting the occurrence of an additional iatrogenic component to the
      intoxication. They also complained of symptoms not associated with the
      theophylline toxicity, which may have diverted the physician's attention from
      recognizing this concurrent problem.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7826682
TI  - Elimination studies of antipyrine and its metabolites in healthy Saudi Arabians.
AB  - 1. We measured the antipyrine clearance in 18 healthy Saudi subjects and
      determined the urinary excretion of three of its metabolites: 4-hydroxyantipyrine
      (4-OH AP), norantipyrine (NOR AP) and 3 hydroxymethylantipyrine (3-OHM AP) in 21
      subjects. 2. The mean +/- SD of the antipyrine clearance was 2.4 +/- 1.1 h-1
      (range 1.0-5.5 l h-1) and the corresponding value per kg body weight was 0.6 +/-
      0.2 ml min-1 kg-1. Urinary excretion of antipyrine (AP), 4-OH AP, NOR AP and 3
      OHM AP expressed as a percentage of the oral dose of antipyrine given was 2.8 +/-
      2.2, 14.5 +/- 6.9, 12.3 +/- 5.6 and 7.6 +/- 3.2 respectively. 3. Compared to
      Africans, Saudis preferentially metabolize AP to NOR AP and compared to
      Caucasians to 3-OHM AP, rather than to 4-OH AP. These discrepancies may reflect
      age differences between the study populations rather than genetic or ethnic
      variations.

PMID- 7826683
TI  - Human polymorphonuclear leukocyte chemotaxis as a tool in detecting biological
      early effects in workers occupationally exposed to low levels of n-hexane.
AB  - Human polymorphonuclear leukocytes (PMN) were chosen to measure two cellular end
      points--chemotaxis and respiratory burst--and to verify whether they could
      function as biomarkers of early effect in detecting occupational exposure to n
      hexane of apparently healthy shoe workers, without any electroneuromyographic
      (ENMG) abnormality. Chemotaxis, but not respiratory burst, was found to be
      impaired. A negative linear correlation between chemotaxis of PMN of those
      workers that had been exposed to n-hexane versus 2,5-hexanedione (2,5-HD) urinary
      concentrations were found. This negative trend is consistent with our previous in
      vitro experimental findings: it was observed that the progressive addition of 2,5
      HD to PMN suspensions inhibited chemotaxis in a dose-dependent mode, while
      chemiluminescence was not modified. Now we have confirmed in vivo that chemotaxis
      is more sensitive than the respiratory burst response to 2,5-HD. Such results
      justify the interest in the behaviour of PMN harvested from workers exposed to n
      hexane. Since significant inhibition of chemotactic activity was observed in some
      workers whose urinary 2,5-HD levels were lower than 5 mg l-1, which is the
      biological exposure index suggested by ACGIH, this study suggests that PMN
      chemotaxis may be proposed as a useful biomarker in detecting occupational
      exposure to low level of n-hexane.

PMID- 7826684
TI  - Accuracy of admission and pre-autopsy clinical diagnoses in the light of autopsy
      findings: a study conducted in Budapest.
AB  - Pre- and post-autopsy diagnoses of underlying cause of death were compared in
      consecutive autopsies on persons aged 30 to 80 years; 1000 from each of two
      pathology departments in Budapest. Data on admission diagnoses and on
      contributory causes of death were also analysed. At autopsy, the percentages of
      deaths by underlying cause were neoplasms (any site) 34.9%, diseases of the
      circulatory system 40.2%, digestive system 13.8%, endocrine, nutritional,
      metabolic or immune systems 2.7%, and respiratory system 2.2%. For these five
      disease groupings, the percentages of cases diagnosed clinically as the
      underlying cause of death which were confirmed at autopsy were, respectively,
      90.9%, 84.0%, 82.9%, 55.2% and 32.5%. Although, out of 697 cases with an autopsy
      diagnosis of neoplasia as the underlying cause, there were only 61 (8.8%) where
      neoplasms were not diagnosed clinically as the underlying cause, this conceals
      the fact that in 130 (18.7%) the two diagnoses differed as to the site of the
      primary neoplasm (ICD 3 digit code). The fact that 43% of post-mortem diagnoses
      (ICD major category) of underlying cause are missed on admission, and that 19%
      are missed clinically, indicates that improved clinical diagnostic procedures
      have not diminished the need for high autopsy rates. Morbid anatomy needs to be
      better resourced.

PMID- 7826685
TI  - Poisoning due to Savlon (cetrimide) liquid.
AB  - 1. Seven adult cases of deliberate oral exposure to 'Savlon' liquid
      (chlorhexidine gluconate 0.3%, cetrimide 3%) are presented. 2. In six patients,
      the symptoms were relatively mild including nausea, vomiting, sore throat and
      abdominal pain. 3. One patient who had concomitantly taken 'Dettol' liquid was
      comatose and hypotensive at presentation and was complicated by aspiration
      pneumonia and adult respiratory distress syndrome (ARDS). She was ventilated for
      a total of 10 days and was hospitalised for 5 weeks. 4. The data from this study
      suggest that symptoms associated with Savlon poisoning are usually mild. When
      aspirated, Savlon together with 'Dettol' liquid can cause ARDS.

PMID- 7826686
TI  - Viper bites in France: clinical and biological evaluation; kinetics of
      envenomations.
AB  - 1. A second inquiry was conducted in France to collect more accurate
      epidemiological, clinical and biological data from patients hospitalized after a
      viper bite, as well as treatment that they received. Fifty-seven well documented
      cases were classified in four grades of increasing severity defined according to
      the clinical signs of envenomation. 2. Local and systemic signs of envenomation
      appeared during the first 3 h, but the severity of the envenomation was observed
      to increase during the 12-24 h following bites in 50% of moderate and severe
      cases. One fatal case was reported. Biological analysis revealed an
      hyperleukocytosis in patients with moderate and severe envenomations. 3. The
      average length of hospitalization was of 1.7 +/- 1.3 days for patients without
      signs of envenomation (grade 0) or presenting a minimal envenomation (grade 1),
      and statistically longer, 6.2 +/- 2.9 days, for patients presenting moderate
      (grade 2) or severe envenomation (grade 3). 4. Levels of venom antigens in serum
      samples regularly collected during hospitalization were determined by a sandwich
      ELISA test. The serum venom levels determined during the first 4 h following the
      bite correlated with the severity of the envenomation when the symptoms were
      determined at their worst, usually 12-24 h later. In fact, concentrations higher
      than 20 ng ml-1 predict a moderate or severe clinical evolution. 5. The
      pharmacokinetics of venom antigens was also investigated during human
      envenomations.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7826687
TI  - Chronic nephrotoxicity of soluble nickel in rats.
AB  - 1. Male and female Wistar rats were given 100 mg L-1 of nickel (as nickel
      sulfate) in drinking water for 6 months. Lactate dehydrogenase, total proteins, N
      acetyl-beta-D-glucosaminidase (NAG), albumin and beta 2-microglobulin were
      measured in 24 h urine after 3 and 6 months of exposure. Body and kidney weights
      were also recorded. 2. After 6 months, urinary excretion of albumin in control
      and exposed rats was 354 and 1319 micrograms 24 h-1 for female rats (P < 0.05)
      and 989 and 2065 micrograms 24 h-1 for male rats (P = non significant). Kidney
      weights were significantly increased in the exposed groups. No significant
      changes were observed in other parameters. 3. The results suggest that low-level
      oral exposure to soluble nickel either induces changes of glomerular permeability
      in female and possibly in male rats, or enhances the normal age-related
      glomerular nephritis lesions of ageing rats. The intake was probably not high
      enough to induce significant tubular changes. The female rat seems to be more
      sensitive to the nephrotoxic effect of nickel than the male rat.

PMID- 7826688
TI  - Stress and the single cell. Fluorescence microtopography of oxidative stress in
      lung ischaemia-reperfusion.

PMID- 7826689
TI  - Molecular crossroads in thyroid tumorigenesis. Molecular genetics of human
      thyroid neoplasms.

PMID- 7826690
TI  - Cryptic 3-D images. Three-dimensional computerised analysis of epithelial cell
      proliferation in the gastrointestinal tract.

PMID- 7826691
TI  - Free radicals on the mind. Hydrogen peroxide mediates amyloid beta protein
      toxicity.

PMID- 7826692
TI  - Phylogenesis and genetic complexity of the nonhuman primate retroviridae.
AB  - The three known groups of nonhuman primate retroviruses (simian immunodeficiency
      virus, simian T cell lymphotropic/leukemic virus type I, and simian foamy virus)
      are thought to have equivalent human counterparts. This is clearly the case with
      human immunodeficiency virus types 1 and 2, the causative agents of acquired
      immunodeficiency syndrome, and with human T cell lymphotropic/leukemia virus type
      I (HTLV-I), which causes T cell leukemia and a progressive form of myelopathy
      (tropical spastic paraparesis/HTLV-I-associated myelopathy), and HTLV-II.
      However, the presence of spumaviruses (foamy viruses) in humans remains
      uncertain. Data accumulated in the last 5 years suggest the possibility that the
      human retroviruses are indeed the result of transmission of simian retroviruses
      to humans. In this article we attempt to parallel the genetic features of the
      simian retroviridae with their human counterparts and argue for the possibility
      of horizontal transmission of these viruses from monkeys to humans.

PMID- 7826693
TI  - Inhibition of alloreactive cytotoxic T cell activity by HIV-positive sera:
      potential role of circulating soluble HLA class I molecules.

PMID- 7826694
TI  - Binding of glycoprotein 120 and peptides from the HIV-1 envelope by
      autoantibodies in mice with experimentally induced systemic lupus erythematosus
      and in patients with the disease.
AB  - Systemic lupus erythematosus (SLE) and infection with the human immunodeficiency
      virus type 1 (HIV) are diseases that are characterized by immune dysregulation
      and autoantibody production. In this article we identify and characterize IgG
      antibodies from mice with SLE and SLE patients that bind HIV gp120 and HIV
      envelope-derived peptides. SLE can be induced in susceptible mouse strains by
      immunization with a human monoclonal anti-DNA antibody that bears a common
      idiotype designated 16/6 Id. We tested sera from various strains of mice in which
      experimental SLE was induced by this method, as well as from 93 patients with SLE
      and 31 controls (17 healthy controls, 14 patients with other autoimmune diseases)
      for the presence of antibodies reactive to gp120 by an ELISA. Antibodies reactive
      with gp120 were produced by BALB/c, C3H.SW, AKR, and DBA/2 mice, all of which
      were 16/6 Id immunized and had experimental SLE. C57BL/6 mice, which are
      resistant to induction of SLE by this method, did not produce antibodies reactive
      with gp120 despite 16/6 immunization. Forty-three percent of SLE patients made
      antibodies that bound to gp120 at titers greater than 1:40, whereas 12% of
      healthy control sera (p < or = 0.02) and 14% of patients with other autoimmune
      diseases contained such antibodies (p < or = 0.05). We delineated the specificity
      of this antibody activity by testing for reactivity to six HIV envelope peptides.
      In both mice and SLE patients, sera reactive with gp120 recognized the same three
      envelope peptides. Removal of the anti-DNA antibodies from the sera by DNA
      agarose affinity purification did not change anti-gp120 specificity.

PMID- 7826695
TI  - Enhancement of HIV type 1 infectivity in vitro by capsular polysaccharide of
      Cryptococcus neoformans and Haemophilus influenzae.
AB  - High concentrations of the cryptococcal capsular polysaccharide (CCP) are present
      in the serum, cerebrospinal fluid or both in the majority of AIDS patients
      infected with Cryptococcus neoformans. Because the prognosis of AIDS patients
      infected with cryptococcus is poor, we investigated whether the presence of CCP
      enhanced HIV-1 infection. The presence of CCP markedly increased the infectivity
      of HIV-1-infected H9 cells and subsequent production of infectious HIV-1 and
      formation of syncytia. In addition to enhancing the infectivity of H9 cells
      infected with laboratory isolates of HIV-1, the presence of CCP also increased
      the infectivity of peripheral blood mononuclear cells (PBMCs) infected with
      primary field strains of HIV-1. The in vitro infectivity of PBMCs from 20 of 44
      HIV-1-infected individuals was significantly increased when cultured with CCP.
      Furthermore, HIV-1 was isolated from the PBMCs of three of these individuals only
      when cultured in the presence of CCP. CCP increased the binding of HIV-1 and
      recombinant gp120 to H9 cells and recombinant CD4, respectively. Thus, it is
      possible that the enhancement of HIV-1 infectivity by CCP is due to its capacity
      to increase the adherence of HIV-1 to target cells. Whereas the capsular
      polysaccharide of Haemophilus influenzae also markedly enhanced the infectivity
      of HIV-1, the capsular polysaccharides of C. freundii or S. flexneri had minimal
      effects on the infectivity of HIV-1. This indicated that the capacity to enhance
      HIV-1 infectivity was a property of polysaccharides from some pathogens and not
      others.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7826696
TI  - Infectious virus with reduced cytopathogenicity resulting from persistent
      infection of normal lung fibroblasts by HIV type 1 strains.
AB  - We asked whether HIV-1 had the capacity to establish a persistent infection of
      cultured human diploid fibroblasts. Human strains of normal diploid embryo lung
      fibroblasts were infected with HIV-1 of the HTLV-IIIB and HIV-1P1 strains.
      Infection was followed over time, to analyze HIV expression. Virus production
      (intra- and extracellular virus) was evaluated as follows: ability to form
      syncytia in the C8166 T cell line, production of p24 and other viral antigens
      (ELISA and indirect immunofluorescence), search for a gag sequence in cell DNA by
      the polymerase chain reaction followed by hybridization to an HIV-1-specific
      probe (SK19). Cell-free culture supernatant was used as a virus source to infect
      de novo fibroblasts and C8166 T cells. Infection of cultured fibroblasts with
      either the HTLV-IIIB or HIV-1P1 strain led regularly to the establishment of
      persistently infected cultures. Fibroblast cells were capable of continuous virus
      production for at least 10 months. The released virus was capable of reinfecting
      cultured fibroblasts and of producing cytopathic effects in the C8166 T cell
      line. However, when compared to wild-type strains, the infectious virus derived
      from fibroblasts showed a prolonged replication cycle and a decreased ability to
      form syncytia in the T cell line. Therefore, HIV-1 can establish a persistent and
      productive infection in normal lung fibroblasts. The data are consistent with the
      hypothesis that in vivo, at least in the lung, fibroblasts may represent a virus
      reservoir and that infection of these cells may lead to the production of
      attenuated variants of HIV.

PMID- 7826697
TI  - Differential priming to programmed cell death of superantigen-reactive
      lymphocytes of HIV patients.
AB  - Programmed cell death or apoptosis has been shown to play a central role in CD4+
      T cell depletion following HIV infection. Because most apoptotic signals are
      delivered through T cell receptor stimulation, we investigated whether T cell
      depletion in AIDS is a stochastic phenomenon or if it preferentially affects T
      cell subsets defined by their interaction with superantigens. To address this
      problem we have taken advantage of the exclusive property of superantigens to
      trigger T cells expressing selective sets of T cell receptor V beta elements.
      Here we report that CD4+ T cells from HIV-infected patients can proliferate in
      vitro to T cell receptor mobilization by some superantigens, but not others.
      Furthermore, the failure of T cells to respond to some superantigens was shown to
      be due to an active cell death process that differentially affected T cells
      capable of interacting with different superantigens. The selective programmed
      cell death priming of T cells responsive to particular superantigens, observed in
      this study, suggests that T cell depletion in HIV infection is not simply due to
      the cytopathic effect of the virus. The possible link between programmed cell
      death and T cell receptor variable regions suggested by the present experiments
      may help to better define current models of AIDS pathogenesis.

PMID- 7826698
TI  - Familial transmission and minimal sequence variability of human T-lymphotropic
      virus type I (HTLV-I) in Zaire.
AB  - Our group previously reported a strong familial clustering of HTLV-I-associated
      myelopathy/tropical spastic paraparesis (HAM/TSP) in Zaire, suggesting a familial
      transmission of the virus together with the presence of cofactors. In the present
      study among 84 relatives of 16 HTLV-I-positive or HAM/TSP index cases, we found
      that all 15 seropositive children had a seropositive mother and that all 15
      children with a seropositive father but a seronegative mother were seronegative.
      Lymphocytes of 17 relatives from 2 families with a familial HTLV-I-associated
      neuropathy were tested in 2 polymerase chain reaction (PCR) assays amplifying pol
      and tax/rex gene fragments. The 10 seropositive individuals were PCR positive for
      HTLV-I and the 7 seronegatives were negative in both PCR assays. The PCR results
      showed no evidence for a long lag period between infection with HTLV-I and
      seroconversion. The HTLV-I long terminal repeat (LTR) of these 10 individuals,
      related in the first to the fourth degree, was amplified and sequenced. Identical
      sequences were found within the families except for one woman infected with two
      variants, one being the familial strain and the other a mutated one with a single
      nucleotide substitution in the 755 sequenced nucleotides of the LTR region. The
      family strain and the mutant were both present in two samples taken 1 year apart.
      Together, the HTLV-I serology, PCR, and sequencing results point toward mother-to
      child transmission as the main mode of HTLV-I infection in this population.
      Comparison of the LTR sequences of the two families with other HTLV-I strains
      from different geographical regions shows that the Zairean HTLV-I strains form a
      separate cluster.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7826699
TI  - Viral variability and serum antibody response in a laboratory worker infected
      with HIV type 1 (HTLV type IIIB).
AB  - Molecular clones of HIV-1 were obtained from isolates cultured from peripheral
      blood mononuclear cells (PBMCs) and directly from uncultured PBMCs from a
      laboratory worker accidentally infected with the HIV-1 laboratory strain, HIV
      1(HTLV-IIIB). Envelope sequences corresponding to the first 752 amino acids of
      HIV-1(HTLV-IIIB) clone BH10 were obtained from clones of cultured virus and
      sequenced. Three env clones obtained shortly after infection differed among
      themselves at only seven nucleotide positions, resulting in one amino acid
      substitution and one frameshift mutation. These envelope sequences were as
      similar to the envelope sequences of various IIIB clones as the latter were to
      each other. env divergence increased over the course of infection. However, the
      overall diversity in env clones obtained two or more years after infection was
      still comparable to that among IIIB env clones from the original IIIB culture.
      Multiple clones of partial env gene sequences containing the V3 loop were also
      obtained directly from uncultured PBMCs by polymerase chain reaction
      amplification. The env sequences of these clones were generally similar to those
      of the cultured viruses. Within the V3 region, the earliest isolates retained the
      sequence of the HXB2 clone from IIIB. Clones obtained later showed a progressive
      divergence in V3. An A-to-T substitution within the GPGRAF sequence at the tip of
      the V3 loop was observed within 1 year after infection, and this mutation
      predominated in all subsequent isolates. Antibodies against the V3 loops of IIIB
      and divergent 1987 and 1990 LW isolates appeared simultaneously in laboratory
      worker serum and persisted with no significant differences in titer. Furthermore,
      neutralization studies with autologous sequential sera suggested selection for
      the A-to-T change in V3 was not due to V3-directed antibodies. These results
      demonstrate a surprising homogeneity among env sequences of HIV-1 from an
      infected laboratory worker, perhaps because the initial infection originated from
      a relatively homogeneous population of tissue culture-adapted virus.

PMID- 7826700
TI  - Endemic transmission of HTLV type II among Kayapo Indians of Brazil.
AB  - Serological studies on 926 blood samples from 703 Brazilian Kayapo (Cayapo)
      Indians showed, by conventional definition of HTLV seropositivity, a 28%
      prevalence of human T lymphotropic virus (HTLV) infection, the highest yet
      reported. Immunoblot (WB) and SYNTH-EIA patterns indicate that the predominant
      infecting agent is type II. Of children under 15 years old, 12% were positive,
      and of persons over 60, more than 60%. Perinatal and heterosexual modes of
      transmission offer an adequate explanation of this incidence. Infection in
      infancy may include infection via breast milk from women other than the mother.
      Evidence of new infection in adults is apparent at an earlier age in women than
      in men. This pattern of antibody prevalence was not determined by cohort effects,
      as demonstrated by tests of serial specimens. Enzyme immunosorbent assay (EIA)
      absorbencies were not stable in the paired specimens: five serum pairs reverted
      and mean absorbencies declined over some age ranges. Many specimens with
      relatively high, but less than positive, EIA results were positive by immunoblot
      (WB). This suggests that the standard EIA end point does not identify all
      infected persons. If the WB alone indicates positivity, 47% of the whole
      population, and more than 80% of the older age groups, are infected with HTLV-II.

PMID- 7826701
TI  - Cutaneous disease resembling mycosis fungoides in HIV-infected patients whose
      skin and blood cells also harbor proviral HTLV type I.
AB  - Two homosexual HIV-infected patients with lymphocyte counts of < 50 presented
      with intense pruritus, hyperpigmentation, and skin lesions clinically suggestive
      of the cutaneous T cell lymphoma, mycosis fungoides. On light microscopy, the
      skin biopsies were difficult to interpret because of the sparseness of the
      lymphocytic infiltrates. However, electron microscopy revealed typical Sezary
      cells in the peripheral blood and skin. Cultures of blood mononuclear cells of
      one of the patients generated HTLV-I-like particles. Although both patients
      lacked antibodies to HTLV, their blood and skin specimens proved to harbor tax
      and pol HTLV-I proviral sequences as shown by the polymerase chain reaction and
      Southern blot analysis. Dual infection with HIV and HTLV should be considered in
      the diagnostic work-up of patients at risk, even in the absence of demonstrable
      antibodies. Dual infections could result in clinical manifestations and evolution
      of disease not anticipated in patients who harbor only one of these retroviruses.

PMID- 7826702
TI  - Feline immunodeficiency virus infection of macrophages: in vitro and in vivo
      inhibition by dideoxycytidine-5'-triphosphate-loaded erythrocytes.
AB  - Although HIV-1 and other mammalian lentiviruses infect macrophages, they are not
      cytopathic. Consequently, these infected long-lived cells serve as major virus
      reservoirs with a key role in the propagation of the virus throughout the body as
      well as in the pathogenesis of AIDS. Furthermore, well-differentiated macrophages
      possess low abilities to phosphorylate the most common reverse transcriptase
      inhibitors of the nucleoside analog family. In an attempt to overcome these
      problems we have evaluated in vitro and in vivo in a feline immunodeficiency
      animal model whether it is possible to protect macrophages from FIV infection by
      direct administration of dideoxycytidine-5'-triphosphate (ddCTP). Because the
      cell membranes are impermeable to phosphorylated drugs we have encapsulated ddCTP
      into autologous erythrocytes. The drug-loaded erythrocyte membranes were then
      modified to target these carrier cells to macrophages. ddCTP-loaded erythrocytes
      were able to reduce FIV production by macrophages infected in vitro or obtained
      from naturally or experimentally infected cats. Furthermore, the administration
      of ddCTP-loaded erythrocytes protected the majority of peritoneal macrophages
      during a 7-month experimental FIV infection and reduced the percentage of
      circulating lymphocytes stained by an anti-p24 antibody. These results suggest
      that the administration of nucleoside analogs in phosphorylate form is feasible
      and their targeting to macrophages reduces FIV infection both in vitro and in
      vivo.

PMID- 7826703
TI  - HIV type 1 V3 sequence diversity in contact-traced Swedish couples at the time of
      sexual transmission.

PMID- 7826704
TI  - Phylogenetic analysis of a new chimpanzee lentivirus SIVcpz-gab2 from a wild
      captured chimpanzee from Gabon.

PMID- 7826705
TI  - [A 37-year-old man with memory loss, homonymous hemianopsia, and elevation of
      anti-herpes simplex virus antibody titer].
AB  - We report a 37-year-old man who presented memory loss, homonymous right
      hemianopsia, and elevation of anti-herpes simplex antibody titer. He had an auto
      accident in January 1992 in that the car he was driving slipped down a 3 m slope;
      his car was severely damaged, however, he himself was not injured. Shortly after
      this accident, he went out of his house less often than before, and he noted some
      difficulty in his vision. He changed his glasses twice, but his vision was
      unchanged. In July of 1992, he had an onset of difficulty in recent memory and
      disorientation to time. He also noted diplopia, and difficulty in seeing objects
      in his right visual field. He was admitted to our hospital on August 26 of the
      same year. General physical examination was unremarkable. On neurologic
      examination, he was alert but disoriented to time and place; calculation was also
      impaired. Mini-mental state examination was 18/30. He had no aphasia, apraxia, or
      agnosia. He showed a tendency to neglect his left side. Optic fundi and visual
      acuity were normal; right homonymous hemianopsia was present. Ocular movement was
      moderately restricted to most of the directions; pupils were isocoric and reacted
      to light promptly. He complained of diplopia in right gaze, and monocular
      nystagmus was induced in his right eye upon right lateral gaze. Trigeminal nerves
      appeared intact. Minimum left facial weakness was present. The remaining of the
      cranial nerves appeared intact. His gait was wide-based and tandem gait was
      impossible. Muscle strength was normal as was the muscle tone. Finger to nose and
      heel to knee tests were done normally.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7826706
TI  - [Treatment of neurological disorders with botulinum toxin].

PMID- 7826707
TI  - [Cerebral circulation in the aged].

PMID- 7826708
TI  - [Collateral venous channels in occlusion of deep cerebral veins and sinuses].
AB  - The authors report on the relationship between occlusion or stenosis of the deep
      cerebral veins and sinuses and the development of collateral venous channels in
      pineal region tumors. Five cases of meningioma arising from the falcotentorial
      junction were the subject of this study. There were two males and three females
      with an average age of 51.2 years (range: 26-67). The straight sinus (SS) and
      posterior part of the great vein of Galen (GVG) were included in the occlusion or
      stenosis of the deep cerebral veins and sinuses in 3 cases, the GVG, SS and
      posterior part of the internal cerebral vein in 1, and the SS alone in 1. The
      various types of collateral venous channels following the occlusion could be
      classified a type 1, from the basal vein of Rosenthal (BVR) to the petrosal vein
      via the lateral mesencephalic and/or anterior pontomesencephalic veins; type 2,
      via the veins on the medial surface of the parietal and/or occipital lobe to the
      superior sagittal sinus (SSS); type 3, dilated superficial anastomotic veins;
      type 4, via the posterior fossa venous circulation to the transverse sinus or the
      SS; and type 5, via the falcian veins to the SSS. The first three types of
      collateral venous channels seem to be important following occlusion or stenosis
      of deep cerebral veins and sinuses. Stereoscopic angiograms are essential to
      analyze deep venous channels around deep-seated tumors. Clear identification of
      occlusion or stenosis and the development of venous system collaterals on
      angiograms is important to the surgical treatment of pineal region tumors.

PMID- 7826709
TI  - [Three patients of complicated form of autosomal recessive hereditary spastic
      paraplegia associated with hypoplasia of the corpus callosum].
AB  - We report three patients with slowly progressive spastic paraplegia and dementia;
      MRI on these patients revealed hypoplasia of the corpus callosum. The mode of
      inheritance was supposed to be autosomal recessive. Patient 1 (26-year-old man)
      is an elder brother of patient 2 (21-year-old man). Their parents are first
      cousins. Patient 3 (woman), a sporadic case, died of pneumonia at the age of 44.
      Their motor development after the birth was normal, but patient 3 was mildly
      mentally retarded. Gait disturbance due to spastic paraplegia developed at the
      age of nine (patient 2), fifteen (patient 1) and nineteen (patient 3),
      respectively. They also showed slowly progressive mental deterioration. Patient 1
      has also suffered from mild amyotrophy and sensory disturbance in the distal part
      of the extremities since the age of 25. Patient 3 was bed-ridden at the middle of
      her thirty's because of generalized amyotrophy and sensory disturbance in
      addition to spastic quadriplegia and profound dementia. Their MRI reveal the
      thinning of the corpus callosum. We think the thinning must be hypoplasia of the
      corpus callosum, because the cerebrum showed normal appearance on MRI in patient
      1 and patient 2. These clinical findings and imaging studies are essentially
      similar to those of the cases reported by Iwabuchi et al (1991). We propose
      autosomal recessive HSP associated hypoplasia of the corpus callosum as a new
      type of HSP.

PMID- 7826710
TI  - [Immunohistochemical study on the expression of copper and zinc-superoxide
      dismutase (Cu, Zn-SOD) in human adenohypophysis and pituitary adenomas].
AB  - A location of copper and zinc- superoxide dismutase (Cu, Zn-SOD) in
      adenohypophysis and pituitary adenomas was examined with immunohistochemical
      technique. Pituitary adenomas include thirteen functioning, five nonfunctioning;
      functioning adenomas consist seven prolactinomas, four growth hormone (GH)
      secreting, two adrenocorticotropic hormone (ACTH) secreting adenomas. Three
      specimens of normal adenohypophysis were used for control study. The Cu, Zn-SOD
      was localized diffusely in the cytoplasm of normal adenohypophyseal cells and the
      tumor cells. Sometimes immunoreactive products of Cu, Zn-SOD revealed in the
      cytoplasm of endothelial cell, neutrophil, macrophage and the cell membrane of
      erythrocyte in the vessels. The content of Cu, Zn-SOD in normal adenohypophyseal
      cells and pituitary adenomas was markedly higher in normal cells than adenoma
      cells. No significant difference of the SOD content was observed not only in non
      functioning adenoma but also in functioning adenoma cells including PRL, GH and
      ACTH cells.

PMID- 7826711
TI  - [Superacute changes in blood-brain barrier following cerebral venous hypertension
      due to an embolic occlusion of cerebral venous sinus].
AB  - Pathophysiological mechanism of hemorrhagic infarction and brain edema following
      obliteration of venous outflow tract has been poorly understood. We analyzed a
      superacute change of the blood-brain barrier in a rat experimental model of
      venous hypertension produced by an embolic occlusion of superior sagittal sinus
      (SSS). In all thirty-seven animals received retrograde embolization, marked
      increments of SSS pressure were noted immediately after embolic occlusion of the
      sinus. Severity and geographical patterns of the disruption of blood-brain
      barrier were then analyzed photomicrographically, visualized by the
      autofluorescence of the exuded Evans blue with Hematoxylin-eosin stain.
      Relationship between the degree of SSS pressure increment and the severity of the
      blood-brain barrier destruction was studied. In ten out of the seventeen animals
      (59%), analyzed five minutes after embolization, exudation of the dye was
      demonstrated. The degree of SSS pressure increment in the animals with dye
      exudation was higher than in the animals without them. In five out of the nine
      animals (56%), analyzed fifteen minutes after embolization, exudation of the dye
      was also demonstrated. The degree of SSS pressure increments in the animals with
      dye exudation was statistically higher than those in the non-exuded ones.
      Especially, all the animals with SSS pressure higher than 75 mmHg were associated
      with severe exudation of the dye. The exudation of the dye was more prominent in
      the white matter than in the cortical gray matter. Following pathological
      analysis have revealed that exudation of the dye was most prominent around the
      capillary and the venule in the white matter. Microvacuolation around these
      vessels was also noted.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7826712
TI  - [Ultrastructural morphological changes of cortical microvessels following
      transient cerebral ischemia--a transmission electron microscopic study].
AB  - Post-ischemic hypoperfusion may play a significant role in reperfusion injury.
      Since there is no established treatment for hypoperfusion, however we decided to
      explore the morphological cause of post-ischemic hypoperfusion. In this study we
      used transmission electron microscopy to investigate the capillaries in
      ischemic/reperfused neocortex induced by 2 hours of middle cerebral artery
      occlusion followed by either 3 or 24 hours of reperfusion in 14 cats. Post
      ischemic hypoperfusion was confirmed by measuring regional blood flow through a
      cranial window just above the left ectosylvian gyrus, which has poor anastomosis.
      A greater number of endothelial microvilli and capillary endothelial cell
      swelling were detected in the ischemic/reperfused neocortex, when compared with
      contralateral control neocortex. Especially after 24-hour reperfusion, collapse
      of some capillaries was observed with severe perivascular glial swelling and
      adhesion of PMN leukocytes to the endothelium. These findings yielded the
      following statistically significant results. 1) The number of endothelial
      microvilli in the ischemic/reperfused neocortex (mean +/- SD/1 blood vessel =
      6.58 +/- 4.32) was significantly greater than in the control neocortex (3.13 +/-
      2.68, p = 0.0001). 2) The ratio of capillary inner diameter (ID) to outer
      diameter (OD) in the ischemic/reperfused neocortex (ID/OD%, mean +/- SD = 75.4 +/
      16.7) was significantly smaller than in the control neocortex (89.2 +/- 10.8, p
      = 0.0001), indicating endothelial cell swelling. We concluded that these
      ultrastructural changes might be the cause of the multifactorial development of
      post-ischemic hypoperfusion, and that especially the number of endothelial
      microvilli and the endothelial cell swelling ratio might serve as morphological
      indicators of therapeutic efficacy for reperfusion injury in experimental
      studies.

PMID- 7826713
TI  - [Results of superficial temporal artery-middle cerebral artery anastomosis for
      elderly and non-elderly patients with cerebral ischemia].
AB  - A study was performed to compare the follow-up results of superficial temporal
      artery-middle cerebral artery anastomosis between a group of nine elderly
      patients (aged 70 years or over) and another group of 24 non-elderly patients
      (aged less than 70 years) with cerebral ischemia. The 33 patients, comprising 26
      males and seven females, were evaluated pre- and postoperatively by four-vessel
      angiography, CT scan, MRI and cerebral blood flow (CBF) examination using either
      xenon inhalation or 123I-IMP SPECT. In some patients, additional evaluations were
      done. For those with dementia, the minimental scale (MMS), P300 event-related
      potential, the Hachinski ischemia score, and the vowel word counting test
      (Kaneko's KANAHIROI) were used, and for the hemiplegic, the Barthel index
      indicating ability of daily life (ADL) was employed. The results of follow-up for
      periods ranging from 12 to 55 months were "excellent" (returned to previous job)
      or "good" (able to perform self-care) in 27 of the 33 patients (81.8%) including
      six (66.6%) of the elderly group and 21 (87.5%) of the non-elderly group. There
      was no significant difference between the two groups by statistical evaluation.
      Among the nine patients with dementia (five under 70, four 70 years of age or
      over), eight (four under 70, four 70 or over) showed "rapid recovery" with
      improved postoperative MMS, P300, vowel word counting score and CBF. One patient
      under 70 (Case 5; a 47-year-old male) with a delayed 2-day recovery from general
      anesthesia, took as long as 6 months to obtain the self-care ability in daily
      life. Excluding this patient, all of the remaining eight patients responded
      quickly to surgery and were able to go home with their families after 2 to 4
      weeks, there being no significant difference between the two age groups. In the
      14 patients with hemiplegia/paresis (nine under 70, five 70 or over), a
      definitely better result was obtained for the non-elderly group. Eight of the
      nine non-elderly patients (89%) showed full ADL (Barthel index 100), whereas only
      one of three elderly patients (33.3%) showed almost full ADL (Barthel index 97).
      In five progressive stroke patients, (three under 70, two 70 or over) ultra-early
      bypass was performed within 8 hours postictus. Definitely better results were
      obtained in the patients aged less than 70, who showed rapid recovery and were
      able to return to their previous jobs 1 to 3 months after surgery. In contrast,
      the two patients aged 70 or over showed no improvement. In this report, we
      discuss the clinical and physiological variables that may be important for
      selection of elderly patients for cerebrovascular bypass surgery.

PMID- 7826714
TI  - [A sporadic case of essential vitamin E deficiency manifested by sensory-dominant
      polyneuropathy and retinitis pigmentosa].
AB  - A 55-year-old woman with known retinitis pigmentosa for 25 years was
      progressively clumsy in gait and activities of daily living over the past 30
      years. She was able to manage house work and social activities, but she developed
      swallowing disturbance associated with involuntary neck muscle spasm for 2 weeks,
      which brought her to our clinic on September 7, 1990. General physical
      examination was normal except for dry skin. Neurological examination was
      compatible with sensory-dominant polyneuropathy, showing distal dominant sensory
      impairment together with absent vibration sense and areflexia in lower limbs, but
      no gross muscular weakness. There were neck dystonia and bilateral poor visual
      acuity due to secondary optic atrophy of retinitis pigmentosa. The former
      responded to the combination of tiapride and trihexyphenidyl. She was admitted
      twice for further evaluation. Complete blood count and blood chemistry tests
      including lipids were all within normal limits, and so was cerebrospinal fluid.
      Pyruvate and lactate before and after exercise loading were also normal.
      Malignancy workup was negative. To our surprise, serum vitamin E level turned out
      very low (1.89 micrograms/ml), normal range being 4.7-20.3 micrograms/ml. Oral
      vitamin E administration test by 2g of alpha-tocopherol showed abnormal
      absorption curve followed fast clearance in serum. Stool was occasionally
      positive for fat corpuscles by Sudan III staining, but 99Tc-HSA leakage into the
      intestines was not detected.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7826715
TI  - [Middle cerebral artery occlusion with unilateral moyamoya like vessels and with
      ruptured anterior cerebral artery aneurysm--its relation to the antiphospholipid
      antibody syndrome].
AB  - We report a case of right middle cerebral artery occlusion associated with
      ipsilateral basal moyamoya like vessels and ruptured anterior cerebral artery
      aneurysm. A 59-year old man suddenly developed a consciousness disturbance and
      was brought to our hospital by ambulance. On admission, computed tomography (CT)
      of the head revealed a diffuse dense high-density lesion in the basal cistern and
      in the bilateral sylvian fissures, and a round homogeneous high-density area in
      the interhemispheric fissure. Subsequent angiography showed a large anterior
      cerebral artery aneurysm and occlusion of the right middle cerebral artery with
      moyamoya-like vessels. We made a diagnosis of subarachnoid hemorrhage due to
      aneurysm rupture. An emergency bifrontal free bone craniotomy was performed,
      utilizing the interhemispheric approach and the neck of the aneurysm was clipped.
      On the 68th postoperative day the patient was ambulatory and discharged from the
      hospital. Hemodynamic stress was thought to be the main cause of the anterior
      cerebral artery aneurysm. Because the laboratory data on admission included a
      false-positive serological test for syphilis, we tested the patient for
      antiphospholipid antibodies, and repeatedly found anticardiolipin antibody in the
      patient's serum. The antiphospholipid antibody syndrome may have been responsible
      for the occlusion of the middle cerebral artery, in this patient and we think
      that testing for serum antiphospholipid antibodies is important in occlusive
      cerebral artery disease, especially in moyamoya disease or when moyamoya-like
      vessels are present.

PMID- 7826716
TI  - Making research readable.

PMID- 7826717
TI  - Expert validation and differentiation of the nursing diagnoses anxiety and fear.
AB  - In this study, the author (a) identifies and validates critical and supportive
      characteristics of the nursing diagnosis anxiety, and (b) differentiates the
      defining characteristics of the nursing diagnosis anxiety from the nursing
      diagnosis fear. The sample consisted of 233 nurses with a master's degree in
      psychiatric-mental health nursing or medical-surgical nursing. The study design
      followed the nurse validation model of Gordon and Sweeney (1979) as expanded by
      Fehring (1986, 1987). Following concept analyses of anxiety and fear, the author
      developed three instruments for rating characteristics as to how representative
      they were of fear or anxiety. Three critical defining characteristics were
      identified for anxiety and six critical defining characteristics were identified
      for fear. Nurses differentiated between the two diagnoses but also suggested the
      presence of a fear-anxiety syndrome in some clients.

PMID- 7826718
TI  - Predicting violence: nursing diagnosis versus psychiatric diagnosis.
AB  - Predicting violent behavior is a major concern for nurses as well as other mental
      health professionals. Two diagnostic assessment systems (Nursing Diagnosis-NANDA
      and Psychiatric Diagnosis-DSM III-R) were compared in their ability to predict
      assaultive behavior. The nursing diagnosis potential for violence suggested a
      difference (p = .07) between the assaultive and control subjects. No differences
      were found between assaultive and control subjects on psychiatric diagnoses.
      Nursing diagnosis is based upon measurable behaviors and is time specific.
      Clinical implications and further research endeavors in this area are suggested.

PMID- 7826719
TI  - Case study: nursing diagnosis in crosscultural settings.

PMID- 7826720
TI  - Validation of the defining characteristics of potential for violence.
AB  - A high incidence of violence occurs in contemporary society, which is reflected
      in the violence exhibited by psychiatric patients. To validate the defining
      characteristics of potential for violence, 125 registered nurses were asked to
      rate the relevance of defining characteristics of the diagnosis. A diagnostic
      content validity index was used to ascertain which defining characteristics the
      nurses believed to be the most critical in the identification of violence
      potential. Nine major and 20 minor characteristics were identified by these
      nurses.

PMID- 7826721
TI  - Use of nursing diagnosis with population groups.
AB  - The authors report findings of a study done to examine the use of nursing
      diagnosis by community health nurses (n = 15) and students (n = 20) who worked
      with population groups. Results of the analysis of the open-ended questionnaires
      and student assignments indicate that many of the diagnoses, both wellness and
      deficit, could be classified in relation to the concepts present in published
      classification systems. Issues raised by the study about the use of nursing
      diagnosis with population groups include: incorporating wellness diagnoses in the
      NANDA Taxonomy, identifying when a group diagnosis is appropriate, determining
      whether to give priority to a behavioral or an environmental focus, and selecting
      the level of abstraction.

PMID- 7826722
TI  - Support for the nursing process.

PMID- 7826724
TI  - [Wage negotiations: arguments for equal pay and equal position in arbitration.
      Interview by Kjell Arne Bakke].

PMID- 7826723
TI  - [Superfluous in Sweden--in demand in Norway. Going after nurses in Sweden.
      Interview by Karin Anne Aase].

PMID- 7826726
TI  - [Occupational health nurses left out. Interview by Kjell Arne Bakke].

PMID- 7826725
TI  - [Baerum City: nurse managers have to wages. Interview by Kari Anne Aase].

PMID- 7826727
TI  - [We want cooperation, not professional conflict. Interview by Kjell Arne Bakke].

PMID- 7826728
TI  - [Nursing under a different sky--Iceland].

PMID- 7826729
TI  - [Wellbeing in colors. Interview by Kari Anne Aase].

PMID- 7826730
TI  - [New colleagues for nurses].

PMID- 7826731
TI  - [We should be neighborhood environmental workers. Interview by Kjell Arne Bakke].

PMID- 7826732
TI  - [West-Agder Central Hospital: 3 million saved "without saving"].

PMID- 7826733
TI  - [School health services: half a minute each].

PMID- 7826734
TI  - [With awakening sexuality. Interview by Marit Fonn].

PMID- 7826735
TI  - [Fewer abortions. Interview by Marit Fonn].

PMID- 7826736
TI  - [Practical education in Gambia].

PMID- 7826737
TI  - [Superfluous in Sweden--in demand in Norway. Triple the number of Swedish
      nurses].

PMID- 7826738
TI  - [Superfluous in Sweden--in demand in Norway. Many apply to the NSF (Norwegian
      Nurses Association)].

PMID- 7826739
TI  - [Superfluous in Sweden--in demand in Norway. A Swede with a Norwegian job.
      Interview by Marit Fonn].

PMID- 7826740
TI  - [Unemployed in Sweden--shortage in Norway].

PMID- 7826741
TI  - [Flexible nurses in part-time. Not as individual in rotation. Interview by Kjell
      Arne Bakke].

PMID- 7826742
TI  - [Flexible nurses in part-time. Trondheim township: possible to do more in full
      time. Interview by Karin Anne Aase].

PMID- 7826744
TI  - [Part-time among women in Norway and the European Community].

PMID- 7826743
TI  - [Unwanted in large fraction: principle case about part-time and equality.
      Interview by Marit Fonn].

PMID- 7826745
TI  - [Campaign on effort for equal pay].

PMID- 7826746
TI  - [Inconvenient working hours does not provide work time reduction].

PMID- 7826747
TI  - [Unequal treatment of pregnant women].

PMID- 7826748
TI  - [Nursing under a different sky--Jerusalem].

PMID- 7826749
TI  - [Predictive tests--to know or not to know...].

PMID- 7826750
TI  - [The right to be a child--also in the hospital].

PMID- 7826751
TI  - [When children are in the hospital. Interview by Bjorn Arild Ostby].

PMID- 7826752
TI  - [77 offspring--they nevertheless took super-exam].

PMID- 7826753
TI  - [Her nurse's dream was fulfilled. Interview by Bodil M. Skarseth].

PMID- 7826754
TI  - [Overrun by nurses. Interview by Bodil M. Skarseth].

PMID- 7826755
TI  - [Like a satellite. Interview by Marit Fonn].

PMID- 7826756
TI  - [Cursed--but has not given up. Interview by Aashild Andal Sandberg].

PMID- 7826757
TI  - [Rogaland county township: takes challenges for more full-time positions].

PMID- 7826758
TI  - [Flexible nurses in part-time. Getting a big job break].

PMID- 7826759
TI  - [Danish nurses in line for permission].

PMID- 7826760
TI  - [Patients evaluate work by employees].

PMID- 7826761
TI  - [No invasion of foreign specialty nurses. Interview by Kjell Arne Bakke].

PMID- 7826762
TI  - [Privately employed nurses: occupational health nurses lose wage fight].

PMID- 7826764
TI  - [With a clinical ear].

PMID- 7826763
TI  - [Care for the aged on a timetable].

PMID- 7826765
TI  - [Nursing college gets departments. Interview by Kari Anne Aase].

PMID- 7826766
TI  - [Life together in hard work].

PMID- 7826767
TI  - [Report in the smoking corner].

PMID- 7826768
TI  - [Nursing under a different sky--Faroe Islands].

PMID- 7826769
TI  - [Fight against pharmaceutical companies].

PMID- 7826770
TI  - [A dignified life for the weakest].

PMID- 7826771
TI  - [Adopted children are more often sick].

PMID- 7826772
TI  - [Away from the old labels. Interview by Marit Fonn].

PMID- 7826774
TI  - [Nurses deprived of right to strike].

PMID- 7826773
TI  - [Faster help to children. Interview by Elisabeth Lund].

PMID- 7826775
TI  - [Health visitors get approval by Health Administration].

PMID- 7826776
TI  - [Support for Palestine health system. Interview by Marit Fonn].

PMID- 7826777
TI  - [Croatia: in contact with life].

PMID- 7826778
TI  - [Cheated out of equal pay].

PMID- 7826779
TI  - Chronic pelvic pain.

PMID- 7826780
TI  - Resistant hypertension and preoperative silent myocardial ischaemia in surgical
      patients.
AB  - We studied 325 patients undergoing elective noncardiac surgery who had
      preoperative ambulatory ECG monitoring performed for a duration of 5130 h (range
      8-24 h; mean 15.8 h). Sixty-four subjects (20%) had one or more episodes of ST
      segment depression consistent with myocardial ischaemia. Of all preoperative
      cardiovascular variables measured, the presence of elevated arterial pressure,
      despite patients being maintained on long term antihypertensive therapy, was the
      only factor associated significantly with the presence of preoperative silent
      myocardial ischaemia (P < 0.002). This correlation was confirmed when arterial
      hypertension was defined in four separate ways. The incidence of silent ischaemia
      in these patients was 33-55%. We suggest that admission arterial pressure may
      therefore be a useful screening test to identify patients at risk of preoperative
      myocardial ischaemia.

PMID- 7826781
TI  - Changes in end-expiratory lung volume on induction of anaesthesia with
      thiopentone or propofol.
AB  - To determine the effects of induction agent and obesity on the change in
      functional residual capacity caused by induction of anaesthesia, we measured the
      change in end-expiratory respiratory volume (EERV) during induction of
      anaesthesia with either thiopentone or propofol. Female patients breathed via a
      face mask from a closed circle system connected to a water spirometer. The
      spirometer tracing was used to measure the decrease in EERV. The median decrease
      was 200 (95% confidence limits 90-280) ml after thiopentone and 285 (200-425) ml
      after propofol. The decrease in each group was significant (P < 0.01) but there
      was no difference between the two groups. The change in EERV, expressed as a
      proportion of the predicted functional residual capacity, was not related to
      obesity (estimated as the ratio of actual to predicted body weight).

PMID- 7826782
TI  - Effects of surgical stimulation on the apnoeic thresholds for carbon dioxide
      during anaesthesia with sevoflurane.
AB  - Mechanical hyperventilation may produce hypocapnic apnoea below the carbon
      dioxide off-switch threshold whereas an increase in arterial PCO2 after post
      hyperventilation apnoea causes reappearance of respiratory effort above the
      carbon dioxide on-switch threshold. To study the effects of surgical stimulation
      on these two thresholds, we have measured end-tidal PCO2 (PE'CO2) at the two
      thresholds, before and during surgical stimulation, in 14 patients undergoing
      mastectomy, anaesthetized with sevoflurane (1.2 MAC). Based on the
      reproducibility of the results, data from 11 patients were analysed and data from
      the three other patients were discarded. Before surgical stimulation, mean
      resting PE'CO2' off-switch threshold and on-switch threshold were 5.7 (SEM 0.2),
      5.2 (0.2) and 6.1 (0.2) kPa, respectively. The off-switch threshold was
      significantly less than resting PE'CO2 (P < 0.01) but the on-switch threshold was
      significantly greater than resting PE'CO2 (P < 0.01). During surgical
      stimulation, resting PE'CO2' off-switch threshold and on-switch threshold were
      4.8 (0.2), 4.1 (0.2) and 4.7 (0.2) kPa, respectively. Although the off-switch
      threshold was significantly less than resting PE'CO2 (P < 0.01), there were no
      significant differences between resting PE'CO2 and on-switch threshold. These
      results indicate that surgical stimulation does not affect equally the carbon
      dioxide on- and off-switch thresholds.

PMID- 7826783
TI  - Effect of humidification on inhalation induction with isoflurane in children.
AB  - A well practised technique is important in achieving quiet induction of
      anaesthesia in children, but the volatile agent used also influences the process.
      Isoflurane results in more airway problems than halothane but recent studies have
      described several ways of improving the acceptability of isoflurane for
      inhalation induction of anaesthesia. We have studied the effect of humidification
      of inspired gases on respiratory complications and hypoxic episodes during
      induction. Forty-one children undergoing inhalation induction of anaesthesia with
      isoflurane and nitrous oxide in oxygen were allocated randomly to receive either
      humidified or non-humidified gas. Humidification did not result in a lesser
      incidence of problems. These findings are contrary to the results in a similar
      study in a predominantly adult sample which demonstrated a significantly lower
      incidence of complications using humidified gases.

PMID- 7826784
TI  - Comparison of the effects of sevoflurane and halothane on the quality of
      anaesthesia and serum glutathione transferase alpha and fluoride in paediatric
      patients.
AB  - We have compared sevoflurane and halothane anaesthesia in paediatric patients
      with reference to induction and recovery. We also assessed hepatocellular
      integrity by measurement of serum glutathione transferase alpha (GSTA)
      concentration and sevoflurane metabolism by serum fluoride concentration. Fifty
      unpremedicated 5-12-yr-old children were allocated randomly to induction of
      anaesthesia via a face mask with 66% nitrous oxide in oxygen and sevoflurane (up
      to 7%) or halothane (up to 3.5%). Anaesthesia was maintained for 1.8 h at 1-1.2
      MAC of the volatile agent. Children receiving sevoflurane had significantly
      faster induction and recovery variables than those receiving halothane. There was
      a small postanaesthetic increase in GSTA in both groups, suggesting that
      halothane and sevoflurane may disturb hepatocellular integrity. Serum
      concentrations of fluoride were significantly greater after sevoflurane than
      after halothane anaesthesia. There were no clinical signs or symptoms of hepatic
      or renal disturbance. Children tolerated sevoflurane better than halothane, which
      may have been because of the nonpungency of sevoflurane and the rapid psychomotor
      recovery after anaesthesia.

PMID- 7826785
TI  - Assessment of intubating conditions in children after induction with propofol and
      varying doses of alfentanil.
AB  - We have assessed tracheal intubating conditions in 60 ASA I or II children, aged
      3-12 yr, after induction of anaesthesia with alfentanil 5, 10 or 15 micrograms kg
      1, followed by an induction dose of propofol. Neuromuscular blocking agents were
      not given. Three aspects of intubating conditions were assessed on a four-point
      scale: ease of laryngoscopy, vocal cord position and degree of coughing on
      insertion of the tracheal tube. The number of patients in whom each component of
      the assessment was satisfactory increased significantly as the dose of alfentanil
      increased (ease of laryngoscopy P = 0.003; vocal cord position P = 0.0004; degree
      of coughing P = 0.018). Intubation was successful in 70%, 95% and 95% of patients
      after alfentanil 5, 10 or 15 micrograms kg-1, respectively, and conditions were
      considered to be excellent in 20%, 70% and 80% of patients, respectively. Side
      effects included pain on injection of propofol (27%), excitatory movements (5%)
      and bradycardia (1.7%).

PMID- 7826786
TI  - Effects of oral nizatidine on preoperative gastric fluid pH and volume in
      children.
AB  - We have studied the effect of oral nizatidine 6 mg kg-1 in total on preoperative
      gastric fluid pH and volume in children. One hundred and four healthy children,
      aged 4-11 yr, were allocated randomly to four groups (n = 26): placebo
      administered at 21:00 and 06:30 the night before and on the day of surgery,
      respectively (placebo-placebo: control); nizatidine 6 mg kg-1 at 21:00 and
      placebo at 06:30 (nizatidine-placebo); placebo at 21:00 and nizatidine 6 mg kg-1
      at 06:30 (placebo-nizatidine); and nizatidine 3 mg kg-1 at 21:00 and 06:30
      (nizatidine-nizatidine). Each child ingested a large volume of apple juice 3 h
      before estimated induction of anaesthesia. After induction of anaesthesia, pH and
      volume of gastric fluid obtained via an orogastric tube were measured. Mean pH in
      the placebo-nizatidine and nizatidine-nizatidine groups was significantly higher
      than that in the placebo-placebo group (5.7 (SEM 0.3), 6.0 (0.3) vs 1.8 (0.2),
      respectively) (P < 0.05). Mean pH in the nizatidine-placebo group was similar to
      that in the control group (2.3 (0.3) vs 1.8 (0.2)). The number of children with
      pH < 2.5 and volume > 0.4 ml kg-1 in the nizatidine-nizatidine (0%) and placebo
      nizatidine (4%) groups was reduced compared with the control (46%) or nizatidine
      placebo (38%) group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7826787
TI  - Synergism between atracurium and vecuronium in infants and children during
      nitrous oxide-oxygen-alfentanil anaesthesia.
AB  - This study was undertaken to see if infants are more sensitive than children to a
      combination of atracurium and vecuronium in an equipotent dose ratio: (microgram:
      microgram) 5:1 in infants and 4:1 in children. We studied 15 infants (1-11 months
      old) and 15 children (3-10 yr old) during nitrous oxide-oxygen-alfentanil
      anaesthesia. Neuromuscular function was recorded by adductor pollicis EMG. An
      individual dose-response curve of the atracurium-vecuronium combination was
      determined for every patient and its potency compared with that of the parent
      agents alone. The combination was significantly more potent than one parent
      agent, both in infants (P < 0.01) and in children (P < 0.0001). However, infants
      were less sensitive than children to synergism produced by the atracurium
      vecuronium combination: if the ED50 dose of the parent agent is defined as one
      dose equivalent, then the mean ED50 doses of the combination were 0.81 (SEM 0.05)
      and 0.64 (0.03) dose equivalents in infants and children, respectively (P <
      0.01). We suggest that an interaction between two binding sites of competitive
      neuromuscular blocking agents in postsynaptic acetylcholine receptors may explain
      both the synergism and sensitivity of infants to non-depolarizing neuromuscular
      blocking agents.

PMID- 7826788
TI  - Neuromuscular and haemodynamic effects of mivacurium in elderly and young adult
      patients.
AB  - We have studied the neuromuscular effects of mivacurium and changes in heart rate
      and arterial pressure in 40 elderly (aged 70 yr) and 20 young adult (aged 18-40
      yr) patients anaesthetized with thiopentone, fentanyl, nitrous oxide in oxygen
      and halothane. Neuromuscular block was monitored by train-of-four (TOF)
      stimulation of the ulnar nerve and recording of the force of contraction of the
      adductor pollicis muscle using a force displacement transducer and a
      neuromuscular function analyser (Myograph 2000, Biometer Ltd). Twenty elderly and
      10 young adults received single doses of mivacurium 0.15 mg kg-1 and spontaneous
      recovery was recorded. The other 20 elderly and 10 adults received the same dose
      but an infusion was started at T1 (first response in TOF) of 10% and the block
      maintained at this level. Haemodynamic effects were studied after administration
      of mivacurium over 15 or 5 s in elderly (n = 10 each) and over 5 s in adult (n =
      10) patients. Onset of maximum block occurred at a mean time of 122 (SD 32) and
      125 (49) s in elderly and young adults, respectively. Recovery of T1 to 25%
      occurred in 22.0 (5.7) and 17.2 (4.4) min, and T1 to 90% in 32.8 (6.9) and 24.4
      (5.8) min in elderly and adult subjects, respectively. Recovery of the TOF ratio
      to 0.7 occurred in 32.8 (7.1) and 26.0 (15.0) min in the elderly and young
      subjects, respectively (all P < 0.05 between young and elderly).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7826789
TI  - Pharmacokinetics of the three isomers of mivacurium and pharmacodynamics of the
      chiral mixture in hepatic cirrhosis.
AB  - We have studied the pharmokinetics of cis-trans, trans-trans and cis-cis
      mivacurium in 10 healthy subjects and 11 patients with mild or moderate hepatic
      cirrhosis, during nitrous oxide-oxygen-isoflurane anaesthesia. Mivacurium 15
      micrograms kg-1 min-1 was infused for 10 min (total dose 0.15 mg kg-1) and the
      plasma concentration of the three isomers measured at regular intervals for 190
      min. The electromyographic response to the drug was also measured. Compartmental
      analysis of the resulting isomer profiles was undertaken: one- and two
      compartment models were fitted to derive clearance, volume of distribution and
      half-life. Clearance of the cis-trans and trans-trans isomers was reduced
      significantly in the cirrhotic compared with the healthy group: cis-trans (median
      (range)) 44 (15-121) ml kg-1 min-1 vs 95 (57-213) ml kg-1 min-1 (P < 0.05); trans
      trans 32 (12-64) ml kg-1 min-1 vs 70 (34-101) ml kg-1 min-1 (P < 0.05). The
      difference in the clearance of the cis-cis isomer in the cirrhotic (4.2 (2.9
      12.1) ml kg-1 min-1) compared with the healthy group (5.2 (2.9-8.9) ml kg-1 min
      1) was not significant with this sample size. Clearance of each isomer correlated
      significantly with plasma cholinesterase activity: cis-trans r = 0.73, P < 0.001;
      trans-trans r = 0.69, P < 0.001; cis-cis r = 0.48, P < 0.05.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7826790
TI  - Extradural analgesia in labour: complications of three techniques of
      administration.
AB  - We have studied the complications associated with three techniques used to
      maintain extradural analgesia in labour: midwife top-up doses of 0.25%
      bupivacaine 10 ml, continuous infusion of 0.125% bupivacaine 10 ml h-1 and
      patient-controlled extradural analgesia (PCEA) with self-administered 3-ml bolus
      doses of 0.25% bupivacaine. A significantly higher intervention rate by an
      anaesthetist was required in the continuous infusion group. There was no
      difference in the mode of delivery between the three groups, although some women
      in the continuous infusion group had significantly denser motor block. There was
      a similar incidence of rectal pressure, unilateral block and missed segments in
      the three groups. Uneventful hypotension occurred in three women; two receiving
      PCEA and one receiving continuous infusion. Ten women experienced sensory blocks
      extending above T7 with no ill effects; seven receiving PCEA and three continuous
      infusion.

PMID- 7826791
TI  - Co-administration of pethidine and clonidine: a spinal anaesthetic technique for
      total hip replacement.
AB  - Co-administration of pethidine 0.75 mg kg-1 and clonidine 75 micrograms
      intrathecally provided good intraoperative anaesthesia for total hip replacement,
      similar to that obtained using 0.5% isobaric bupivacaine. Sensory and motor block
      were of shorter duration than that after 0.5% isobaric bupivacaine and 0.5%
      isobaric bupivacaine with morphine 0.5 mg (P < 0.001 sensory block, P < 0.001
      motor block). Postoperative morphine consumption, measured using a patient
      controlled system, was similar to that in patients in the bupivacaine only group
      (pethidine-clonidine: median 39 mg/24 h; bupivacaine: median 34 mg/24 h) but
      greater than that in the bupivacaine-morphine group (median 8 mg/24 h) (P <
      0.001). Visual analogue pain scores after operation were similar to those with
      bupivacaine alone at all but one of the recording times but were greater than
      those in patients who received bupivacaine and morphine at 4, 6 and 10 h after
      operation (P < 0.001, P < 0.04, P < 0.02). The combination did not offer any
      major advantage over conventional agents.

PMID- 7826792
TI  - Extradural sufentanil by patient-controlled analgesia or nurse-administered
      compared with optimal morphine in a high dependency unit: effects on oxygenation
      and pain relief after abdominal surgery.
AB  - The incidence of apnoeic episodes (> 12 s) was measured in 30 surgical patients
      allocated randomly to one of three analgesic regimens and all nursed in a high
      dependency unit. Ten patients received i.m. morphine (mean 52 (range 30-80) mg),
      administered on request. The remaining 20 patients received extradural sufentanil
      as an initial bolus dose of 50 micrograms followed by a bolus of 10 micrograms,
      either self-administered using PCA (10 patients: mean 275 (range 130-450)
      micrograms) or administered by a nurse on request (10 patients: 144 (70-200)
      micrograms). With i.m. morphine apnoeic episodes were maximal 2-3 h after
      administration while after extradural sufentanil, apnoeas were maximal within a
      few minutes.

PMID- 7826793
TI  - Predictive factors of hyperfibrinolytic activity during liver transplantation in
      cirrhotic patients.
AB  - Hyperfibrinolytic activity occurs frequently during liver transplantation in
      cirrhotic patients. In order to identify those patients at high risk for
      increased intraoperative blood loss before operation, we determined predictive
      indicators of hyperfibrinolysis. We studied 56 cirrhotic patients undergoing
      liver transplantation with the same anaesthetic procedure and transfusion
      regimen. The preoperative coagulation patterns of the 11 patients who experienced
      acute intraoperative hyperfibrinolytic activity were compared with those of the
      45 patients who did not suffer this complication. Before surgery, patients with
      intraoperative hyperfibrinolysis had decreased prothrombin time (PT) and
      euglobulin lysis time (ELT), and increased thrombin time (TT) and fibrinogen
      degradation products (FDP), whereas alpha angle and maximum amplitude (MA) were
      reduced on thrombelastography. Stepwise multivariate analysis disclosed three
      components which were significantly linked with occurrence of hyperfibrinolysis:
      TT, FDP and MA. Their sensitivity, specificity, positive and negative predictive
      values demonstrated that patients with FDP > or = 48 mg litre-1 and MA < or = 35
      mm before incision had 100% probability of developing hyperfibrinolytic activity
      during transplantation.

PMID- 7826794
TI  - Continuous monitoring of depth of sedation by EEG spectral analysis in patients
      requiring mechanical ventilation.
AB  - Twenty-three patients undergoing intensive therapy had continuous EEG recording
      in an attempt to assess depth of sedation using spectral analysis. Median power
      frequency (MPF) and spectral edge frequency (SEF) were calculated and correlated
      with the clinical sedation score and blood concentration of sedative drug.
      Fifteen patients received isoflurane and eight midazolam. There was no
      correlation between MPF or SEF and sedation score or blood concentration of drug.
      These results suggest that no simple measure of the EEG is likely to correlate
      with depth of sedation in critically ill patients.

PMID- 7826795
TI  - Assessment of preformed, coiled-tipped, micro spinal catheter.
AB  - We have developed a preformed, coiled-tipped, microspinal catheter made of
      Teflon, 30-gauge, 90 cm long and with a 3-cm long circled tip of 7 mm in
      diameter. We have studied the problems of using microcatheters, specifically the
      difficulty in placing the catheter and the maldistribution of local anaesthetic.
      In this study we have compared three types of spinal catheter: the new, coiled
      tipped catheter, a standard, straight-tipped catheter and a 32-gauge
      microcatheter (TFX) with a stainless steel stylet embedded in the side wall
      (Microspinal, TFX/Rush Medical, Duluth, GA, USA). The coiled-tipped catheters
      were placed in the subarachnoid space more rapidly and with greater ease than the
      straight-tipped and TFX catheters (100%, 75% and 8% within 2 min, respectively),
      and had the highest success rate in achieving adequate block compared with the
      others (94%, 69% and 64%, respectively).

PMID- 7826796
TI  - Midazolam is metabolized by at least three different cytochrome P450 enzymes.
AB  - Distribution volumes and metabolism determine the pharmacokinetics of midazolam.
      Cytochrome P450 3A4 has been considered a significant enzyme in its metabolism.
      Using heterologously expressed cytochrome P450 enzymes, we have confirmed the
      additional involvement of cytochromes P450 3A3 and 3A5 in the hydroxylation of
      the midazolam. Whereas cytochrome P450 3A3 metabolized midazolam to the same
      extent as cytochrome P450 3A4, cytochrome P450 3A5 increased its metabolism by a
      factor of 2.7. The relationship of alpha- to 4-hydroxylation of midazolam was
      approximately 1.3 for cytochromes P450 3A3 and 3A4, and approximately 8.8 for
      3A5. The primary location of cytochromes P450 3A3 and 3A4 is the liver in
      contrast with cytochrome P450 3A5, which occurs predominantly in the kidney.
      Therefore, further in vivo study is required to prove conclusively that enzymes
      in the kidney are involved in the metabolism of midazolam. Nitrendipine itself is
      metabolized by cytochrome P450 3A enzymes and this was shown to inhibit human
      liver microsomal hydroxylation of midazolam and preferentially alpha
      hydroxylation by about 77%. 4-Hydroxylation was inhibited to 32% of control by
      nitrendipine. In contrast with inhibition of 4-hydroxylation, alpha-hydroxylation
      would appear to be competitively inhibited. These findings may be relevant to
      drug interactions in combined therapy.

PMID- 7826797
TI  - Effect of hypothermia on the in vitro potencies of neuromuscular blocking agents
      and on their antagonism by neostigmine.
AB  - The effect of temperature on the potencies of neuromuscular blocking agents
      remains unclear. This study was undertaken to examine the effects of different
      neuromuscular blocking agents at 37 and 27 degrees C at a constant carbon dioxide
      content (alpha stat principle). The effect of neostigmine 1 mumol litre-1 induced
      antagonism of these agents was also investigated. Phrenic nerve-hemidiaphragm
      preparations of rats were mounted in modified Krebs solution, maintained at 37
      degrees C and aerated with a 5% carbon dioxide-95% oxygen gas mixture, and at 27
      degrees C with 4% carbon dioxide to maintain the carbon dioxide content of the
      solution constant. Phrenic nerves were stimulated with 0.1-Hz supra-maximal
      impulses of 0.2-ms duration and the elicited tension of the diaphragm recorded.
      The potencies of the steroidal neuromuscular blocking agents (rocuronium,
      vecuronium, pancuronium and pipecuronium) increased significantly at 27 degrees C
      (P < 0.05), while the potencies of the benzylisoquinolinium agents (tubocurarine
      and dimethyltubocurarine) did not change. Neostigmine-induced antagonism of the
      steroidal agents did not differ significantly between each other but differed
      significantly from the benzylisoquinolinium agents (P < 0.05) at both
      temperatures. The ratios of IC50 (inhibitory concentration, 50%) with and without
      neostigmine at hypothermia were slightly higher for the steroidal agents,
      indicating slight enhancement of antagonism by neostigmine at 27 degrees C. In
      contrast, the ratios were significantly greater at 27 degrees C (P < 0.05) for
      isoquinolinium agents, implying significant enhancement of antagonism. Our
      results indicate that at 27 degrees C the potency of all steroidal agents
      increased and neostigmine-induced antagonism was slightly enhanced.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7826798
TI  - Cerebral effects of nitrous oxide during isoflurane-induced hypotension in the
      pig.
AB  - We have studied the effects of nitrous oxide on cerebral blood flow (CBF),
      cerebral blood flow velocity (CBFV) and intracranial pressure (ICP) during
      isoflurane-induced hypotension in 10 pigs. CBF was measured using laser Doppler
      flowmetry, CBFV in the right middle cerebral artery was calculated using Doppler
      ultrasound and ICP was measured using an extradural ICP monitor. Each animal was
      studied under four conditions, examined sequentially: (i) mean intra-arterial
      pressure (MAP) 85 mm Hg, maintained with isoflurane, (ii) MAP 50-55 mm Hg,
      induced by isoflurane only, (iii) MAP 85 mm Hg, maintained with isoflurane and
      50% nitrous oxide, and (iv) MAP 50-55 mm Hg, induced by isoflurane and 50%
      nitrous oxide. No significant differences were noted between conditions with
      respect to ICP. There was a significant difference in CBF during condition (ii)
      compared with (i) (mean 75(SD 21) vs 100(0)%) and during condition (iv) compared
      with (iii) (90(26) vs 109(13)%). Animals under condition (iv) exhibited a 20%
      reduction in CBFV compared with those under condition (iii) (57 vs 69 cm s-1).
      For animals under normotensive conditions, addition of nitrous oxide to
      isoflurane resulted in a 16% increase in CBFV (69 vs 60 cm s-1). Comparing
      isoflurane-induced hypotension ((ii) vs (iv)), there was no statistical
      difference in either CBF or CBFV on addition of 50% nitrous oxide. The
      correlation between changes in CBF and CBFV was not significant. We conclude that
      the use of nitrous oxide during isoflurane-induced hypotension has no significant
      effect on CBF, CBFV or ICP compared with the use of isoflurane alone.

PMID- 7826799
TI  - Postoperative delirium in the elderly.

PMID- 7826800
TI  - Use of the laryngeal mask airway after oesophageal intubation.
AB  - We have compared insertion of a tracheal tube and laryngeal mask airway (LMA)
      both with and without the presence of a tube in the oesophagus in 20 ASA I and II
      patients undergoing elective laparoscopy. After induction of anaesthesia and
      neuromuscular block, we measured the times for an experienced anaesthetist to
      correctly position both an LMA and a tracheal tube with and without a tube in the
      oesophagus. The time to intubation was significantly less with the LMA than with
      the tracheal tube, both with and without an oesophageal tube in place (P < 0.05).
      We conclude that if a tracheal tube is placed unintentionally in the oesophagus,
      an LMA may be used subsequently to provide rapid and effective oxygenation of the
      patient.

PMID- 7826801
TI  - Tracheal intubation in a manikin: comparison of supine and left lateral
      positions.
AB  - Tracheal intubation in the left lateral position may be necessary in some
      circumstances. Using a manikin we demonstrated that anaesthetic trainees found
      tracheal intubation in the left lateral position was more difficult and took
      longer than in the supine position. However, the time to successful tracheal
      intubation decreased with practice, indicating the presence of a learning curve.
      We suggest that tracheal intubation in the left lateral position should become
      part of training in the management of the difficult airway.

PMID- 7826802
TI  - Optimum rate of administration of propofol for induction of anaesthesia in rats.
AB  - Twenty rats received propofol 2.5, 5, 10 or 20 mg kg-1 min-1 i.v. Brain activity
      was monitored using the electroencephalogram (EEG). As the endpoint for induction
      of anaesthesia we used a burst suppression period of 1 s or longer. At a fast (20
      mg kg-1 min-1) rate of administration, the induction dose was significantly
      larger compared with a slower rate (10 mg kg-1 min-1). At a slow rate of
      administration (2.5 mg kg-1 min-1), the induction dose was also significantly
      larger compared with a rate of 10 mg kg-1 min-1. In spite of different dose
      requirements at different rates of administration, duration of anaesthesia was
      not significantly different.

PMID- 7826803
TI  - Pulmonary gas exchange during orthotopic liver transplantation.
AB  - The aim of this study was to evaluate the efficiency of pulmonary gas exchange
      during the course of liver transplantation. We studied 25 adult cirrhotic
      patients undergoing transplantation, performed with venovenous bypass. A
      significant increase in PaO2, and a significant decrease in physiological shunt
      and alveolar-arterial partial pressure difference were observed just before the
      start of venovenous bypass. These changes were probably caused by modifications
      in respiratory mechanics, such as an increase in functional residual capacity.
      There were no other respiratory changes during the anhepatic and post-anhepatic
      phases.

PMID- 7826804
TI  - Total tracheal obliteration after intubation with a low-pressure cuffed tracheal
      tube.
AB  - A 22-yr-old male had a head injury after a road traffic accident. His trachea was
      intubated for 5 days with a high-volume, low-pressure cuffed tracheal tube. When
      the trachea was extubated he showed signs of progressive upper airway obstruction
      which were relieved by tracheotomy. Computed axial tomography demonstrated
      complete tracheal obliteration at the previous cuff site. The patient underwent
      resection anastomosis of the destroyed tracheal segment which, on histological
      examination, showed fibrous tissue and bone formation. It is believed that
      excessive cuff pressure was the cause of the damage, as monitoring cuff pressure
      has not yet become a routine practice in anaesthesia and intensive care.

PMID- 7826805
TI  - A universal nitric oxide delivery system.
AB  - A nitric oxide delivery system for adult ventilators has been developed; this is
      designed to maintain a constant inspired nitric oxide concentration of 16 volumes
      per million (vpm) in spite of changes in minute and tidal volumes. In a
      laboratory test the system maintained tracer gas concentrations equivalent to
      nitric oxide 13.8-18 vpm for tidal volumes of 500, 700 and 900 ml, ventilator
      rates of 10, 15 and 20 b.p.m., peak inspiratory flow rates of 30, 40 and 50 litre
      min-1 and square, sine and decelerating ramp flow profiles.

PMID- 7826806
TI  - A standard set of terms for critical incident recording?
AB  - The Anaesthetic Specialty Working Group of the Clinical Terms Project has been
      creating clinical terms for inclusion in the Read clinical classification. It is
      the intention to include terms to describe critical incidents. Many difficulties
      were encountered and these are discussed. The current definitions of a critical
      incident in the anaesthetic literature are too wide to allow a circumscribed set
      of terms to be generated. The interpretation of a critical incident is not only
      subjective but also requires a great deal of contextual information to describe
      it accurately. A method of critical incident reporting using the terms that will
      be contained within the enhanced Read clinical classification is proposed. These
      terms may be useful in the construction of a nationwide critical incident
      register.

PMID- 7826807
TI  - Antagonizing residual neuromuscular block with neostigmine and atropine.

PMID- 7826808
TI  - Neostigmine and postoperative nausea.

PMID- 7826809
TI  - Neostigmine and postoperative nausea.

PMID- 7826810
TI  - Neuromuscular block and tourniquets.

PMID- 7826811
TI  - Oral and subcutaneous administration of cadmium chloride and the distribution of
      metallothionein and cadmium along the villus-crypt axis in rat jejunum.
AB  - The route of Cd uptake influences the distribution of Cd, other metals, and
      metallothionein (MT). Although intestinal MT levels related to the tissue mass
      did not show proximodistal gradients after sc administration of CdCl2, orally
      administered high doses of CdCl2 increased mucosal MT levels longitudinally from
      the duodenum to the ileum. The gradient abolished when the mucosal MT level was
      related to the intestinal length. To further elucidate this finding, three groups
      of rats were studied: a control group, a group receiving dietary CdCl2, and a
      group receiving sc injections of CdCl2. The small intestine was removed after a
      14-d treatment. Midjejunal segments were mounted in a cryomicrotome and cut
      transversally into five layers along the villus-crypt axis. Mucosal enzymes were
      measured to control these sections. Cd was measured by AAS and MT by RIA.
      Alkaline phosphatase and lactase activities exhibited the typical villus-crypt
      gradient. Mucosal MT levels paralleled those of Cd. Although Cd and MT
      concentrations were high at the tip of the villi and low in the crypts after oral
      administration, sc treatment reversed that profile. A molar Cd-MT ratio of approx
      10 or 1 was reached after po or sc treatment, respectively. This demonstrates
      that only oral Cd may lead to an accumulation of Cd in the mucosal tissue fairly
      exceeding the binding capacity of small intestinal MT. The results show that
      different routes of Cd intake lead to a different MT-induction pattern in the
      intestinal wall and that longitudinal Cd and MT concentration gradients in the
      small intestine observed after high oral doses are a result of their high levels
      at the villus tips.

PMID- 7826812
TI  - Disturbances of morphological parameters in blood of rats orally exposed to
      aluminum chloride.
AB  - The aim of this work was to assess changes of morphological parameters in the
      blood of rats after oral (po) administration of aluminum (Al), in relation to the
      time and the administered dose. The experiment was performed on female Wistar
      rats. The animals were administered aluminum chloride (100 mg Al/kg) daily for 21
      d. Morphological assays: red blood cells (RBC), hemoglobin (HGB), hematocrit
      (HCT), iron serum concentration (Fe), MCH, MCHC, absolute corrected reticulocyte
      count (ACRC), white blood cells (WBC), and platelet count (PLT) were estimated on
      d 3, 7, 14, and 21, both in the control group and in intoxicated rats. After wk 1
      of aluminum administration we observed a decrease of RBC, HCT, HGB and serum iron
      concentration in the blood of rats. The increase of the platelet count was
      observed earlier than changes in other parameters. Investigation has proved that
      the exposure of rats to aluminum administered orally results in normocytic
      anemia.

PMID- 7826813
TI  - Effects of inorganic arsenicals on DNA synthesis in unsensitized human blood
      lymphocytes in vitro.
AB  - Effects of inorganic arsenicals on DNA synthesis in unsensitized human blood
      lymphocytes were biphasic: The chemicals at very low concentrations enhanced DNA
      synthesis, whereas higher concentrations inhibited DNA synthesis. The
      concentrations of arsenicals at which the maximum stimulating effect was found
      were 1 x 10(-5) M, 1 x 10(-6) or 2 x 10(-6) M, and 0.8 x 10(-6) or 1 x 10(-6) M
      for sodium arsenite exposure of 1 h, 3 d, and 6 d, respectively; for sodium
      arsenate, 1 x 10(-5) M, 1 x 10(-5) M, and 2 x 10(-6) or 5 x 10(-6) M,
      respectively. Arsenicals must be present for the entire 6-d culture period to
      produce maximum stimulation of DNA synthesis in human lymphocytes. The longer
      exposure of the lymphocytes to arsenicals, the lower the concentrations of
      arsenicals at which the maximum stimulating effect on DNA synthesis was found.
      Stimulating effect of trivalent arsenic (sodium arsenite) on DNA synthesis was
      stronger than pentavalent arsenic (sodium arsenate), and the stronger the effect
      of trivalent arsenic than pentavalent, the longer exposure of the cells to the
      chemicals. Both sodium arsenite and sodium arsenate stimulated DNA synthesis in
      human lymphocytes to a lower degree than phytohemagglutinin (PHA).

PMID- 7826814
TI  - Zinc content in selected tissues in streptozotocin-diabetic rats after maximal
      exercise.
AB  - The Zn metabolism in experimental diabetic rats after maximal exercise was
      investigated. Forty male wistar rats were used, weighing 240 +/- 10 g at the
      beginning of this experiment. The animals were assigned to one of four
      experimental groups (n = 10): control at rest (CR), control plus exercise (CE),
      diabetic at rest (DR), and diabetic plus exercise (DE). Experimental diabetes was
      produced by a single intraperitoneal injection of streptozotocin (STZ) (60
      mg/kg). Thirty days after injection of streptozotocin, the animals of groups CE
      and DE were forced to acute exercise (swimming) until exhaustion. Glucose, rectal
      temperature (RT), pH, swimming time (ST), hematocrit (Hct), serum, and tissue
      (heart, liver, kidney, and muscle) Zn concentrations were measured. The
      streptozotocin treated animals used in the current experiment were diabetic.
      Increases in hepatic, renal, muscle, and serum levels Zn at rest and after
      exercise until exhaustion were found in normal and diabetic rats. ST decreased (
      180%) in the diabetic rat group. In conclusion, the results of the present study
      indicate that STZ-induced diabetes was associated with altered tissue Zn
      concentration, both at rest and after exercise.

PMID- 7826815
TI  - Dietary zinc-methionine enhances mononuclear-phagocytic function in young
      turkeys. Zinc-methionine, immunity, and Salmonella.
AB  - The ability of dietary zinc-methionine (Zn-Met) to enhance mononuclear-phagocytic
      function against Salmonella arizona and enteritidis was investigated in young
      turkeys. Feed/gain and body wt gain at 21 d of age were not affected by Zn-Met.
      The addition of 30 or 45 ppm Zn from Zn-Met to a Zn adequate diet significantly
      increased cutaneous basophil hypersensitivity to phytohemagglutinin-P. The
      clearance of intravenously administered S. enteritidis from blood was not
      affected by 30 ppm of supplemental Zn from Zn-Met. However, 30 ppm Zn from Zn-Met
      increased the reduction of intravenously administered S. arizona from spleen.
      Percentages of myeloid and mononuclear-phagocytic cells before and after S.
      enteritidis infection were not affected by supplemental Zn-Met. Turkeys
      supplemented with Zn-Met showed enhanced in vitro phagocytosis of S. enteritidis
      by Sephadex-elicited abdominal exudate cells. The phagocytosis of S. arizona was
      unaffected by Zn-Met.

PMID- 7826816
TI  - The distribution of BrK alpha/RbK alpha peak intensity ratio in human whole blood
      samples. Comparison between normal and colorectal cancer cases.
AB  - A preliminary study was conducted to compare the BrK alpha/RbK alpha peak
      intensity ratio in colorectal cancer (CRC) patients and healthy subjects
      (controls) in Israel. Blood samples were obtained from 61 CRC patients and 124
      controls. The controls represent a normal population from different areas in
      Israel. Three hundred microliters of wet whole blood samples were analyzed by the
      EDXRF method. A weighted mean of 2.45 +/- 0.38 Br/Rb ratio was obtained for CRC
      patients, as compared with 3.28 +/- 0.40 Br/Rb ratio for controls. The mean value
      for controls represents only 112 subjects, since 12 individuals of the control
      group suffered from some other diseases and therefore were not included for the
      mean value calculation in this group. The results indicate that the Br/Rb ratio
      in CRC patients is significantly lower (p < 0.05) than in controls. No
      significant difference was found in Br/Rb ratio correlated to age and sex. It was
      not possible to draw final conclusion concerning the relationship between the
      Br/Rb ratio and the malignancy stage, since there was a relatively small number
      of cases in each stage under investigation.

PMID- 7826817
TI  - Manganese stimulates the oxidative burst of differentiated HL-60 cells.
AB  - Incubation with manganese results in a twofold increase in the oxidative burst of
      differentiated HL-60 cells. This stimulation was characterized by examining the
      dose response, length of incubation time, and specificity of manganese. Manganese
      only stimulated the burst in cells induced to differentiated with retinoic acid
      and not in undifferentiated HL-60 cells. Incubation with manganese did not result
      in a greater number of differentiated cells. The maximum stimulation occurred at
      0.2 mumol/L manganese. Stimulation of the oxidative burst required 96 h of
      incubation with manganese, since cells incubated with the same levels of
      manganese for the last 24 h of culture did not result in any stimulation.
      Magnesium, present in the incubation medium at physiological serum levels (820
      mumol/L) also stimulated the oxidative burst, whereas iron (0.3 mumol/L), zinc
      (18 mumol/L), and copper (12 mumol/L) had no effect. To determine whether
      manganese and magnesium stimulated the burst differently, the initial rates of
      superoxide anion production was determined. The initial rate of the reaction
      proceeded rapidly in cells incubated with manganese, whereas there appeared to be
      a lag before magnesium-treated cells produced superoxide anion. Thus, manganese
      seems to stimulate the oxidative burst differently than magnesium.

PMID- 7826818
TI  - Accumulation of platinum in the intervertebral discs and vertebrae of ovarian
      tumor-bearing patients treated with cisplatin.
AB  - Platinum was determined by the inductively coupled plasma mass spectrometry (ICP
      MS) in the intervertebral discs and vertebrae of ovarian tumor bearing patients
      treated with cis-diamminedichloro-platinum (II) (cisplatin). Platinum was 0.05
      ng/mL at the absolute detection limit, and platinum was undetectable in the
      intervertebral discs and vertebrae of human specimens without cisplatin
      treatments. On the other hand, platinum was detected in the intervertebral discs
      and vertebrae of patients administered cisplatin, and platinum concentration was
      at levels of 1.06-10.31 micrograms/g dry tissue in the intervertebral discs and
      0.60-1.28 micrograms/g dry tissue in the vertebrae, respectively. The platinum
      level of intervertebral discs was 4.3-fold higher than that of the vertebrae.
      Thus, platinum accumulates greatly in the intervertebral discs and somewhat in
      the vertebrae after administering cisplatin to patients for therapy.

PMID- 7826819
TI  - Clinical pharmacology, physiology and pathophysiology of superficial veins--1.
AB  - 1. Venous resistance contributes very little to total peripheral resistance; more
      than half of the total blood volume, however, is contained in the extrathoracic
      veins. Owing to marked differences between venous and arterial anatomy and
      physiology, studies on veins and arteries usually require different
      methodological approaches. Whereas for arteries the most relevant parameters are
      resistance, pressure and flow, for veins volume and compliance are most
      important. For studies of general aspects of the peripheral circulatory system,
      venous occlusion plethysmography is probably the most useful method. The
      determination of both the rate of rise in limb volume and the total volume rise
      after inflating a proximally applied occlusion cuff to a subdiastolic pressure
      permits the concomitant estimation of both arterial flow and venous compliance.
      2. Studies of direct pharmacological or physiological effects on veins,
      interactions of various pharmacological or physiological stimuli, or
      pathophysiological changes in venous responsiveness have been facilitated by the
      development of investigational techniques relying on direct measurements of the
      compliance of single human veins in vivo. One of these, relying on the use of a
      linear variable differential transformer (LVDT) for determining changes in the
      compliance of superficial veins at a standardized congestion pressure, has been
      found very suitable for the practical application in both patients and healthy
      subjects. 3. Physiological studies were carried out on the effect of age,
      exercise, temperature, and the menstrual cycle on venous compliance and venous
      responsiveness to various stimuli. In addition, interindividual variability in
      venous responsiveness in monozygotic and dizygotic twins and in unrelated
      subjects was investigated, and studies on the function of the endothelium were
      carried out in man in vivo. 4. Pathophysiological studies using this technique
      were reported from patients with hypertension, orthostatic hypotension,
      myocardial infarction, varicosis, cystic fibrosis, asthma, diabetes, systemic
      sclerosis, and cluster headache. 5. Clinical pharmacological studies represent a
      most important field for the use of this method. Studies were carried out on the
      effects of a large number of constrictor and dilator agents, and also on drug
      interactions on human veins in vivo. Venoconstriction was observed after local
      administration of alpha-adrenoceptor and 5-HT-receptor agonists, ergot
      derivatives, angiotensinogen, angiotensin I and II, and several prostaglandins.
      6. Owing to the low venous tone present under effects can usually be quantified
      only on veins e.g. noradrenaline or 5-hydroxytryptamine. Under these conditions
      dilatation was observed after the administration of beta-adrenoceptor agonists,
      cholinergic (muscarinic) agonists, nitrates, calcium antagonists, bradykinin,
      substance P and several prostaglandins.

PMID- 7826820
TI  - Nitric oxide mediated venodilator effects of nebivolol.
AB  - 1. Nebivolol, a selective beta 1-adrenoceptor antagonist with antihypertensive
      effects, has haemodynamic effects suggestive of a direct vasodilator action. 2.
      The dorsal hand vein technique was used to determine whether nebivolol has
      venodilator action in vivo in man. 3. Nebivolol and atenolol were infused into
      the phenylephrine preconstricted superficial hand veins of 11 healthy male
      volunteers. In separate studies L-NMMA (0.1 microgram min-1) was pre- and co
      infused with nebivolol to determine whether nitric oxide (NO) mediated mechanisms
      were present. Further studies with prostaglandin F2 alpha (PGF2 alpha)
      preconstriction were performed to exclude an alpha-adrenergic antagonistic effect
      of nebivolol. Effects of L-NMMA infusion on nitroglycerin venodilation were also
      determined. 4. Nebivolol produced a dose dependent venodilation, (72 +/- 18%
      maximum), whereas atenolol produced no significant venodilation. At doses of
      nebivolol producing plasma concentrations comparable with plasma levels achieved
      after standard oral dosing (10(-13)-10(-12) mol min-1) small (14 +/- 6% and 23 +/
      8%) but significant (P < 0.05) venodilation was observed. 5. The venodilator
      response to nebivolol was significantly reduced by infusion of L-NMMA (maximum
      dilation 18% vs 72%, P < 0.01). Venodilator responses to nitroglycerin were
      unaffected by L-NMMA infusion. A venodilator effect to nebivolol was also seen
      following preconstriction with PgF2 alpha (40 +/- 20% maximum). 6. Nebivolol has
      nitric oxide mediated, venodilator effects in man.

PMID- 7826821
TI  - The pharmacokinetics and pharmacodynamics of quinine in the diabetic and non
      diabetic elderly.
AB  - 1. Quinine is a front-line antimalarial drug but is prescribed most commonly in
      nonmalarious countries for cramps. Postural hypotension, hearing loss and
      hyperinsulinaemic hypoglycaemia occur in malaria and overdose but little is known
      of quinine kinetics and toxicity in the elderly. 2. We studied 12 non-insulin
      dependent diabetics and 10 non-diabetic controls aged 51-79 years. Subjects
      attended on two occasions > 7 days apart. On each test day, subjects were given a
      600 Cal meal at 18.00 h (0 h) and, on one occasion, quinine sulphate 600 mg at
      22.00 h (4 h). Venous blood samples for glucose, insulin and quinine assay were
      drawn pre-prandially and then regularly over the next 38 h. Supine and erect
      blood pressures were taken and audiometry was performed at 4, 6, 8 and 14 h. A
      one-compartment open pharmacokinetic model was fitted to serum quinine
      concentrations. 3. Absorption and elimination half-times, volume of distribution
      and oral clearance of quinine were comparable in the two groups (P > 0.2) and
      there was a mean absorption lag-time of approximately 1 h. Basal and immediate
      post-prandial (< 4 h) serum glucose and insulin concentrations on both test days
      were similar in the diabetics and also in the non-diabetics, but quinine produced
      a mean reduction in serum glucose of 1.0 mmol l-1 from 3-5 h post-dose in both
      groups without affecting serum insulin concentrations. Quinine administration did
      not alter postural blood pressure changes or produce significant hearing loss in
      either group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7826822
TI  - Pharmacokinetic and pharmacodynamic properties of a long-acting formulation of
      the new somatostatin analogue, lanreotide, in normal healthy volunteers.
AB  - 1. The aims of the study were to assess the pharmacokinetic parameters and the
      hormonal effects of the slow-release formulation of the somatostatin analogue (SR
      L) in normal male volunteers. 2. Eight healthy males were studied. For the
      determination of basal values blood was sampled before the injection of vehicle
      and then every other hour for 8 h in order to measure plasma GH, prolactin (PRL),
      TSH, free thyroxin (fT4), insulin and glucagon levels. Plasma insulin-like growth
      factor 1 (IGF-1) levels were measured on a single sample. On day 1 of the study,
      30 mg SR-L was administered intramuscularly. Blood was drawn just before
      injection and then every other hour for a period of 8 h. Thereafter, blood was
      sampled three times a week for 3 weeks in order to measure lanreotide, IGF-1,
      TSH, fT4 and PRL concentrations. Plasma GH was determined on days 6 and 11 of the
      study. 3. Plasma lanreotide concentrations rose to 38.3 +/- 4.1 ng ml-1 2 h
      following injection. The levels then progressively decreased, remaining above 1.5
      ng ml-1 until day 11 and reaching 0.92 +/- 0.28 ng ml-1 2 weeks after injection.
      The apparent plasma half-life and mean residence time were 4.52 +/- 0.50 and 5.48
      +/- 0.51 days respectively. 4. By comparison with the control day, plasma insulin
      concentrations only decreased 2 h following injection, whereas plasma glucagon
      did not change at any time. 5. Plasma TSH concentrations were significantly (P <
      0.01) reduced from 2 h to day 4 following SR-L injection.2+ '

PMID- 7826823
TI  - The stereoselective disposition of the enantiomers of ibuprofen in blood, blister
      and synovial fluid.
AB  - 1. A sensitive, stereospecific assay using gas chromatography-mass spectrometry
      (GC/MS) was established to measure the concentrations of the enantiomers of
      ibuprofen in small volumes (50 microliters) of blister fluid. 2. The
      concentrations of the enantiomers in blister fluid, assessed in eight patients,
      were similar to those in synovial fluid, both fluids behaving as peripheral
      compartments with respect to plasma. 3. The mean rate constants of transfer of R
      ibuprofen into (0.14 +/- 0.06 h-1) and out of (0.20 +/- 0.04 h-1) blister fluid
      were not significantly different from those for synovial fluid (0.19 +/- 0.12 h
      1, 0.34 +/- 0.11 h-1, respectively). Similarly, the mean rate constants of
      transfer of S-ibuprofen into (0.22 +/- 0.07 h-1) and out of (0.27 +/- 0.08 h-1)
      blister fluid were not significantly different from those for synovial fluid
      (0.29 +/- 0.10, 0.36 +/- 0.11 h-1). However, the correlations were poor between
      the transfer constants for each of the enantiomers between plasma, and both
      blister and synovial fluid (P > 0.2). 4. The complex rate constant of transfer of
      S-ibuprofen into blister fluid (0.22 +/- 0.07 h-1) was greater than that of R
      ibuprofen (0.14 +/- 0.07 h-1), which may be explained by the lesser protein
      binding of the S-enantiomer.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7826824
TI  - Inability to detect plasma etretinate and acitretin is a poor predictor of the
      absence of these teratogens in tissue after stopping acitretin treatment.
AB  - 1. Concentrations of etretinate, acitretin and its main metabolite 13-cis
      acitretin were measured in plasma and subcutaneous fat samples from 37 women of
      childbearing age exposed to acitretin before November 1990. Twenty of the women
      still used acitretin and 17 had stopped therapy for a period ranging from 1 to 29
      months. 2. The prevalences of detectable etretinate concentrations were 45% and
      83% in plasma and subcutaneous tissue, respectively, among current acitretin
      users and 18% and 86% among those who had stopped acitretin therapy. Thus,
      inability to detect plasma etretinate is a poor predictor of the absence of
      etretinate in fat. 3. Acitretin and/or etretinate were detectable in fat and in
      some cases in plasma from women who had ceased acitretin therapy for up to 29
      months. 4. We suggest that (cis)-acitretin and etretinate should be monitored in
      subcutaneous tissue when plasma measurements are negative. The recommended
      contraception period of 2 years after cessation of acitretin therapy should be
      reconsidered to avoid the risk of teratogenicity.

PMID- 7826825
TI  - Transfer of dideoxyinosine across the human isolated placenta.
AB  - 1. Dideoxyinosine (ddI) has recently been approved for the treatment of patients
      with HIV infection. As increasing numbers of such patients are pregnant, we
      wished to define the rate and mechanism(s) of ddI transfer by the placenta to the
      foetus. Using isolated single perfused human term placental cotyledons, the drug
      was shown to cross the placenta from mother to foetus at a rate of 25% that of a
      freely diffusible marker, antipyrine, and at about half the rate of zidovudine
      (AZT). The transfer of ddI was similar in both directions (maternal to foetal and
      the reverse), equal to that of L-glucose, a passively transported sugar, and was
      not inhibited by excess inosine or uric acid (structural analogues of ddI). ddI
      did not cross to the foetus against a concentration gradient. The transport
      process appeared to be passive and it was not altered by AZT. 2. ddI was not
      metabolized in the Krebs Ringer buffer/albumin perfusate, and placental
      homogenates converted only 4% of ddI to hypoxanthine over the 4 h incubation.
      However, when maternal term or cord blood was incubated with ddI for 3 h, 50% of
      the drug was converted to hypoxanthine in maternal blood and to hypoxanthine and
      uric acid in cord blood. 3. Thus, ddI metabolism in maternal blood should
      decrease its net transfer to the foetus in vivo. In the foetal circulation, ddI
      will be further metabolized by erythrocytes to hypoxanthine and possibly to uric
      acid. Hence, the fraction of administered ddI delivered to foetal tissues should
      be much lower than that of AZT.

PMID- 7826826
TI  - The role of CYP2D6 in primary and secondary oxidative metabolism of
      dextromethorphan: in vitro studies using human liver microsomes.
AB  - 1. The enzyme kinetics of dextromethorphan O-demethylation in liver microsomes
      from three extensive metabolisers (EM) with respect to CYP2D6 indicated high (Km1
      2.2-9.4 microM) and low (Km2 55.5-307.3 microM) affinity sites whereas microsomes
      from two poor metabolisers (PM) indicated a single site (Km 560 and 157 microM).
      Similar differences were shown for 3-methoxymorphinan O-demethylation to 3
      hydroxymorphinan (Km 6.9-9.6 microM in EM subjects; Km 307 and 213 microM in PM
      subjects). 2. Dextromethorphan O-demethylation was inhibited competitively by
      quinidine (Ki 0.1 microM), rac-perhexiline (Ki 0.4 microM), dextropropoxyphene
      (Ki 6 microM), rac-methadone (Ki 8 microM), and 3-methoxymorphinan (Ki 15
      microM). These compounds were also potent inhibitors of 3-methoxymorphinan O
      demethylation with IC50 values ranging from 0.02-12 microM. Anti-LKM1 serum
      inhibited both dextromethorphan and 3-methoxymorphinan O-demethylations in a
      titre-dependent manner. 3. The Michaelis-Menten constant for dextromethorphan N
      demethylation to 3-methoxymorphinan (Km 632-977 microM) and dextrorphan N
      demethylation to 3-hydroxymorphinan (Km 1571-4286 microM) did not differ between
      EM and PM microsomes. These N-demethylation reactions were not inhibited by
      quinidine and rac-methadone or LKM1 antibodies. 4. Dextromethorphan and 3
      methoxymorphinan are metabolised by the same P450 isoform, CYP2D6, whereas the N
      demethylation reactions are not carried out by CYP2D6.

PMID- 7826827
TI  - Central effects of the diuretic, bendrofluazide.
AB  - 1. Central effects of the diuretic, bendrofluazide (2.5, 5 and 10 mg) were
      studied in 12 healthy volunteers. Two placebos and an active control drug,
      oxazepam (15 mg), were included. Single doses were administered double-blind at
      10.00 h. The effects of drugs on performance and subjective feelings were
      assessed before and from 1.5-2.5 and 3.5-4.5 h after ingestion, and recording of
      the electrical activity of the brain (EEG) and body sway carried out. 2.
      Performance was assessed using digit symbol substitution, continuous attention,
      letter cancellation, choice reaction time, finger tapping, immediate and short
      term memory, together with critical flicker fusion and two flash fusion. Subjects
      assessed their mood and well-being on a series of 12 visual analogue scales. The
      EEG was recorded with eyes open while the subjects carried out a mental
      arithmetic task, and with eyes closed, when they were required to relax. Body
      sway was recorded with eyes open and with eyes closed. 3. Bendrofluazide (10 mg)
      increased the number of errors at letter cancellation and reduced the rate of
      finger tapping (P < 0.05), while oxazepam increased the number of errors and
      reduced accuracy at continuous attention (P < 0.01), and increased the number of
      involuntary rest pauses during tapping (P < 0.05). 4. There were no effects of
      drugs on subjective assessment of mood. 5. No changes in the electrical activity
      of the brain were observed with bendrofluazide. In recordings with eyes open,
      oxazepam reduced delta (0.5-3 Hz), theta (3.5-7 Hz) and alpha 2 (10.5-13 Hz)
      while increasing beta 1 (13.5-21 Hz) activity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7826828
TI  - Efficacy of a low dose-range of fluvastatin (XU 62-320) in the treatment of
      primary hypercholesterolaemia. A dose-response study in 431 patients. The French
      Dutch Fluvastatin Study Group.
AB  - 1. In this randomised, double-blind, placebo-controlled study, the efficacy of
      four dosages of fluvastatin (2.5, 5, 10 and 20 mg day-1) were assessed in 431
      patients with primary hypercholesterolaemia recruited in 17 centres. 2. Following
      an 8-week dietary stabilisation phase and a 6-week placebo phase, the patients
      were randomised to receive placebo or fluvastatin 2.5, 5, 10 or 20 mg once daily
      at night for a period of 6 weeks. 3. Total cholesterol, beta-quant LDL-C, and the
      beta-quant LDL-C/HDL-C ratio were significantly reduced by all doses of
      fluvastatin, and HDL-C was significantly increased by the 10 mg and 20 mg doses.
      Fluvastatin 20 mg day-1 also significantly decreased TG and Lp(a):B levels. 4.
      Fluvastatin was well tolerated during the study, and relatively few biochemical
      or haematological abnormalities occurred. 5. Of the dosages tested, 20 mg
      fluvastatin day-1 is the optimal hypolipidaemic dose.

PMID- 7826829
TI  - The antinatriuretic action of gamma-L-glutamyl-5-hydroxy-L-tryptophan is
      dependent on its decarboxylation to 5-hydroxytryptamine in normal man.
AB  - 1. The effects of inhibition of peripheral aromatic L-amino acid decarboxylase
      during infusion of the relatively renally selective 5-hydroxytryptamine (5-HT)
      prodrug, gamma-L-glutamyl-5-hydroxy-L-tryptophan (glu-5-HTP), were examined in
      eight healthy male subjects in a randomised, placebo-controlled, cross-over
      study. 2. Each subject received oral carbidopa (100 mg) or placebo followed, 1 h
      later, by a 60 min intravenous infusion of glu-5-HTP (16.6 micrograms kg-1 min-1)
      or placebo. 3. After administration of glu-5-HTP, cumulative urinary excretion of
      5-HT was 430-fold greater than that after placebo, and was associated with a
      period of sodium retention. 4. Pretreatment with carbidopa substantially
      attenuated the increase in 5-HT excretion after glu-5-HTP and abolished its
      antinatriuretic effect. 5. These results are in keeping with the proposition that
      the antinatriuretic action of glu-5-HTP is dependent on its decarboxylation to 5
      HT.

PMID- 7826830
TI  - Morphine and morphine-glucuronide concentrations in plasma and CSF during long
      term administration of oral morphine.
AB  - Concentrations of morphine, morphine-3-glucuronide (M3G) and morphine-6
      glucuronide (M6G) were measured by h.p.l.c. in plasma and cerebrospinal fluid
      (CSF) samples from 16 patients with cancer receiving oral (controlled-release)
      morphine. There was a close correlation between plasma and CSF morphine
      concentrations (r = 0.94, P = 0.0001) and both correlated with drug dosage (r =
      0.61, P = 0.013 and r = 0.74, P = 0.0001, respectively). M3G and M6G in plasma
      and CSF were correlated (r = 0.81 and r = 0.82, both P = 0.0001). No relationship
      was apparent between M plus M6G concentrations in the CSF and pain scores.

PMID- 7826831
TI  - Determination of dose-dependent absorption of amoxycillin from urinary excretion
      data in healthy subjects.
AB  - Measurement of unchanged drug in urine was used to study the rate and extent of
      amoxycillin absorption after administration of amoxycillin sodium solution to six
      healthy subjects in a Latin-Square crossover design. The mean (95% CI) fraction
      of the dose excreted as unchanged amoxycillin decreased (P < 0.05) from 0.50
      (0.44-0.56) after 97 mg amoxycillin sodium (= 0.25 mmol amoxycillin) to 0.23
      (0.19-0.27) after 3103 mg (8 mmol), while the mean residence time determined from
      urinary excretion rate data increased (P < 0.05) from 1.54 (1.32-1.76) h to 2.16
      (2.01-2.41) h. Plots of total urinary excretion and initial (0-30 min) excretion
      of unchanged drug vs dose indicated significant non-linearity above 776 mg doses.
      Michaelis-Menten parameters describing this relationship with respect to amount
      absorbed were 3.02 mmol for maximum amount absorbed and 1.93 mmol for amount
      absorbed at half maximum for 0-30 min. These results support a saturable
      absorption mechanism for amoxycillin which had clinical implications for high
      oral amoxycillin doses, and for competition with other drugs having capacity
      limited absorption.

PMID- 7826833
TI  - Anti-emetic effect of high-dose metoclopramide vs alizapride--a randomised
      crossover study.
AB  - A randomised double-blind crossover study was undertaken to compare the anti
      emetic efficacy of alizapride against high dose metoclopramide. A total of 32
      patients on cisplatin were randomised to receive either high dose metoclopramide
      (7 mg kg-1 day-1) or alizapride (5 mg kg-1 day-1). Anti-emetic responses in terms
      of control of vomiting episodes were similar in both regimens (59%). However,
      patients showed a statistically significant preference for high dose
      metoclopramide (P = 0.02). Side effects of both regimens were minimal. We
      conclude that alizapride is not superior to high dose metoclopramide in
      controlling cisplatin induced vomiting.

PMID- 7826832
TI  - The pharmacokinetics of chloroquine in healthy Thai subjects and patients with
      Plasmodium vivax malaria.
AB  - The pharmacokinetics of chloroquine (CQ) and desethylchloroquine (DECQ) were
      studied in seven male Thai patients with P. vivax malaria and seven healthy male
      Thais, after the standard oral dosage regimen of CQ (a total dose of 1500 mg
      given over 3 days). All patients showed a rapid initial response to the treatment
      with median (range) values of fever and parasite clearance times of 13.7 (2-47)
      and 58 (33-38) h, respectively. In the patients, the median range Cmax value was
      significantly higher (1547 (996-2446) vs 838 (656-1587) ng ml-1), and AUC(0,28d)
      was greater (281 (250-515) vs 122 (103-182) micrograms ml-1 h). In addition, the
      median (AUC(0,28d) of DECQ was significantly greater (170 (72-265) vs 77 (49-140)
      micrograms ml-1 h). The AUC(0,28d) ratio of DECQ to CQ in patients was
      significantly higher than that in healthy subjects (0.67 (0.43-0.90) vs 0.51
      (0.29-0.61)).

PMID- 7826834
TI  - Preliminary study of the efficacy of xamoterol in bradycardia-tachycardia
      syndrome.
AB  - Following 4 weeks on placebo, eighteen patients with bradycardia-tachycardia
      syndrome (BTS) were treated with 100 mg xamoterol twice daily for 2-4 weeks.
      Ambulatory 24 h Holter electrocardiogram recordings showed that xamoterol
      decreased maximum heart rate from 140 +/- 5.1 to 107 +/- 6 beats min-1 (P <
      0.001) during exercise, increased minimum heart rate from 43 +/- 1.7 to 51 +/-
      2.4 beats min-1 (P < 0.005) at night and shortened maximum duration of sinus
      arrest from 3438 +/- 484 to 1767 +/- 202 ms (P < 0.005) in BTS. Symptomatically,
      patients reported that palpitations were improved and syncopal attacks
      disappeared. Although the study has the limitation of an open design, effects of
      treatment were objectively evaluated using Holter monitoring by investigators who
      reviewed the recordings in a blinded manner. The findings suggest that xamoterol
      may be useful in the treatment of BTS. Further studies are needed to evaluate
      fully its therapeutic potential in this condition.

PMID- 7826835
TI  - Effects of age: breast cancer presents differently in young women.

PMID- 7826836
TI  - Pre-antibiotic treatments spur modern fungal infection research.

PMID- 7826837
TI  - Quality of life in osteosarcoma survivors.
AB  - Charts of 89 osteosarcoma survivors from Massachusetts General Hospital and The
      Children's Hospital/Dana Farber Cancer Center, who had received primary treatment
      more than 1 year previously and had no evidence of disease, were reviewed. Sixty
      two patients, mean 12 years from diagnosis, agreed to structured interviews.
      Rates of psychopathology did not differ significantly from the general
      population. High distress was noted in 13%. Twenty-three normal progeny had been
      born postchemotherapy to eight women and the wives of five male patients. One
      pregnancy was complicated by doxorubicin-induced cardiac toxicity. Only two with
      previous childhood tumors believed themselves infertile. All felt the effort to
      save the limb was worthwhile. In most, ongoing pain was mild; phantom pain and
      neuralgia common. Most survivors were in good mental and physical health with the
      capacity to bear children.

PMID- 7826838
TI  - Current status of post-chemotherapy tamoxifen in early breast cancer.
AB  - In the 2 decades since tamoxifen entered clinical practice for breast cancer
      therapy, the clinical application of this agent has evolved from the treatment of
      metastatic disease, to systemic adjuvant therapy, and, recently, to the
      experimental application as a chemoprevention agent. The Early Breast Cancer
      Trialists' Collaborative Group metaanalysis provides compelling evidence of the
      benefits associated with the use of tamoxifen and chemotherapy as separate
      adjuvant modalities in women with stages I and II breast cancer. The role of the
      combined use of chemotherapy and tamoxifen in this analysis, however, is less
      certain. Since chemotherapy and tamoxifen therapy have the potential for life
      threatening toxicities, a critical appraisal of the available literature is
      needed to determine which patient populations would receive additional benefit
      from combined adjuvant chemotherapy and tamoxifen and which questions still need
      to be addressed in clinical trials.

PMID- 7826839
TI  - Clinical trials referral resource. Adjuvant therapy in breast cancer.

PMID- 7826840
TI  - Prevention and management of radiation myelopathy.
AB  - The dramatic nature of radiation-induced spinal cord injury causes clinicians to
      avoid doses that could lead to this complication, sometimes even to the point of
      possibly compromising tumor control. As a consequence, clinical data on radiation
      myelopathy are limited. So far, experimental investigations have been devoted to
      establishing the dose-response, time-dose-fractionation relationships, and volume
      effects for CNS injury in various animal models. Concepts and parameters gained
      from such laboratory studies have been useful for the development of new
      radiotherapy strategies in terms of dose fraction schedules and dose adjustments
      as a function of radiation volumes. Further advances in therapeutic strategies,
      however, must come from elucidation of the pathogenesis of radiation-induced CNS
      injury. Results of recent studies warrant revision of the current concept that
      such injuries result simply from reproductive killing of glial "stem cells" and
      endothelial cells. Emerging evidence indicates that various cell types contribute
      to determining the progression of radiation lesions.

PMID- 7826841
TI  - Hemopoietic stem cell transplants for multiple myeloma.
AB  - Recently, high-dose therapy has been evaluated in patients with multiple myeloma,
      mainly with autologous transplant support. As a result of rapid hemopoietic
      engraftment with peripheral blood stem cells collected after chemotherapy and/or
      hemopoietic growth factor priming, procedure-related mortality has dropped to
      below 5%. When applied within 12 months from initial therapy, autologous
      transplants effect complete remissions in up to 50% of patients, with median
      event-free and overall survival durations on the order of 2.5 and 4 to 5 years,
      respectively. Complete response rates with allogeneic transplantation range from
      30% to 50%, and procedure-related mortality is approximately 40%. Although the
      median durations of event-free and overall survival are shorter with allogeneic
      transplants, approximately 35% to 40% of patients survive with minimal disease
      for at least 5 to 6 years. Direct comparisons of standard therapy and autologous
      transplants have just begun.

PMID- 7826842
TI  - Mesothelioma in childhood.

PMID- 7826843
TI  - Use of total parenteral nutrition in children with cancer: a review and some
      recommendations.
AB  - Total parenteral nutrition (TPN) is now a standard component of supportive
      treatment in many pediatric oncology units for patients undergoing intensive
      therapy. TPN incurs many risks and significant costs, however, that may not
      always be balanced by major benefits. Infection rates are reported to be high in
      patients receiving TPN, and TPN use is associated with a range of metabolic
      problems. With standard TPN regimens, the catabolic state of many intensively
      treated patients may not be adequately reversed. Because TPN may enhance tumor
      cell growth, there is justifiable concern about giving TPN when a cancer patient
      is not also receiving cytotoxic therapy. Recommendations for TPN use in pediatric
      oncology patients include using TPN formulas containing glutamine to stimulate
      anabolism and timing TPN cycles to be given just before cytotoxic chemotherapy,
      when stimulation of tumor growth might actually improve the effectiveness of
      antimitotic chemotherapy.

PMID- 7826844
TI  - Hodgkin's disease in children in the West Midlands, 1957-1986: a large population
      based study.
AB  - One hundred forty-one children were diagnosed with Hodgkin's disease between 1957
      and 1986 in the West Midlands Health Authority Region (1991 population, 1.1
      million children). Eighty-seven were boys and 54 were girls, representing a
      significant male:female ratio of 1.5:1 (P < 0.01). The average age-standardized
      incidence rate was 3.6 per million per year with a significant increase in the
      older age group (> or = 10 years) in the second half of the period (P = 0.02).
      The mixed cellularity subtype was more common in those younger than 10 years,
      with nodular sclerosing disease being seen more in those < or = 10 years. Overall
      survival at 5 years was 76% (65% at 10 years) with a significant difference (P <
      0.001) in survival between the first and last decades. There was six second
      malignancies, five of which could have been treatment related. A positive history
      of cancer in close relatives was found in 11 patients, and higher social class
      was found in more older than younger children. These findings support the
      hypothesis that Hodgkin's disease may have a viral etiology and may be linked
      with socioeconomic conditions.

PMID- 7826845
TI  - Seventeen years of experience with chronic idiopathic thrombocytopenic purpura in
      childhood. Is therapy always better?
AB  - Between 1975 and 1992 450 children with idiopathic thrombocytopenic purpura (ITP)
      were diagnosed, and of those 100 (22%) developed the chronic form of the disease.
      Approximately half the patients with chronic ITP presented with mild to moderate
      hemorrhagic manifestations at the onset of purpura (30 cases) and/or later during
      the course of the disease (25 cases). The incidence of intracranial hemorrhage
      was 1%, and the mortality rate due to overwhelming septicemia after splenectomy
      was also 1%. Overall one-third of the patients received no therapy; two-thirds of
      them went into spontaneous remission within 8 months to 8 years from the onset of
      ITP. Steroids given in conventional or high doses (51 cases) achieved a transient
      (if any) rise in platelet count, but in no case were steroids curative. Remission
      related to intravenous immune globulin (IVIG) therapy was noticed in 38.5% of the
      children (10 of 26) after variable courses. The response rate to splenectomy was
      95.0%. Ultimately the long-term outcome in children with chronic ITP was as
      follows: remission, 58 cases (spontaneous, 30; after IVIG therapy, 10; after
      splenectomy, 18); hemostatic platelet values, 22 cases (spontaneous, 16; after
      IVIG, 5; after splenectomy, 1). Thirteen children were lost in follow-up, and 7
      remain thrombocytopenic but asymptomatic. These data indicate that chronic ITP in
      childhood runs a benign course in most cases and may remit with or without
      therapy even several years from onset. Therefore, therapeutic intervention has to
      be individualized, and splenectomy, which is not always safe, should be reserved
      for problematic cases that fail to respond to conventional therapeutic
      modalities.

PMID- 7826846
TI  - Increased risk of secondary leukemia after single-agent treatment with etoposide
      for Langerhans' cell histiocytosis.
AB  - The study evaluated 139 patients diagnosed with Langerhans' cell histiocytosis
      (LCH) and enrolled in any protocol of the Italian Association of Pediatric
      Hematology/Oncology since 1982. Treatment was etoposide (VP-16) only in 50
      patients, VP-16 and other drugs with an already established leukemogenic effect
      in 17 patients, only drugs with leukemogenic effect in 6 patients, other drugs in
      35 patients, and surgery only in 31 patients. Median length of follow-up after
      diagnosis was 65 months (range, 1 to 126 months) for a total of 742.5 person
      years at risk (PYRs). Three cases of acute myelogenous leukemia (AML) were
      reported; only 0.0044 case was expected. The standard incidence ratio (SIR) of
      AML in this cohort was 680.5 [95% confidence interval (CI), 140.2-1988.5], and
      the incidence rate per 1000 PYRs was 4.0 (95% CI, 0.8-11.8). For the subgroup
      treated with single-agent VP-16, the SIR after treatment was 2270.0 (95% CI, 275
      8199), and the incidence rate after treatment was 14.7 (95% CI, 1.8-42.8). The
      study confirms a higher risk of leukemia after LCH and supports the hypothesis of
      an association between treatment-related acute nonlymphocytic leukemia and single
      agent treatment with VP-16.

PMID- 7826847
TI  - High incidence of hypertension in children presenting with acute lymphoblastic
      leukemia.
AB  - Although hypertension is a complication of acute lymphoblastic leukemia (ALL),
      its true incidence in this disease is unknown. In this study the blood pressure
      profiles in all children newly diagnosed with ALL were reviewed over an 18-month
      period. Fourteen (46%) from a total of 30 patients were found to be hypertensive
      at presentation (n = 8) or during induction chemotherapy (n = 6). A patient with
      significant hypertension developed generalized convulsions; the rest were
      asymptomatic. Six patients were managed with antihypertensive drugs. Four
      patients with hypertension had renal enlargement on the initial ultrasound scan,
      which returned to normal when hematologic remission was achieved. One patient
      without hypertension had bilateral renal enlargement, but this persisted despite
      achieving remission. All patients with hypertension were normotensive at follow
      up 2 to 18 months after induction chemotherapy. The presence of hypertension
      before therapy and its association with renal enlargement suggest that the
      leukemic process is an important etiologic factor. In all cases therapy
      aggravated or unmasked the elevation in blood pressure. Considering the high
      incidence of susceptible patients, increased awareness and prompt management may
      avoid possible life-threatening complications.

PMID- 7826848
TI  - Changes in lactate dehydrogenase isoenzymes associated with relapse of childhood
      acute lymphocytic leukemia.
AB  - Twenty-eight children with high-risk acute lymphocytic leukemia underwent monthly
      serum lactate dehydrogenase (LDH) and LDH isoenzyme fraction determinations to
      examine whether LDH isoenzyme fractions change with an increase in the body
      burden of tumor cells. The 9 patients who relapsed and 5 patients who presented
      with leukemia during the study period had a slightly lower mean LDH-1 isoenzyme
      fraction. When the period from 3 months before to 3 months after relapse was
      examined, significant increases in the LDH-3 isoenzyme fraction and decreases in
      the LDH-1 and LDH-2 isoenzyme fractions were seen at the time of relapse. These
      results were highly significant when patients with non-T-cell and T-cell leukemia
      were combined and when bone marrow and central nervous system relapse was
      included. The changes at relapse appeared to revert with intensification of
      chemotherapy. The changes at relapse were not different in magnitude from random
      variation occurring in patients who remained in remission throughout the study.
      Although changes in LDH isoenzymes appeared to occur at the time of relapse
      compared with the periods immediately before and after relapse, these changes
      were not specific for relapse. LDH isoenzymes do not appear to be useful in
      predicting relapse in children with leukemia.

PMID- 7826849
TI  - Outcome for patients with constitutional 13q chromosomal abnormalities and
      retinoblastoma.
AB  - The outcomes for five patients with retinoblastoma and constitutional chromosomal
      abnormalities involving the long arm of chromosome 13 are reported. All patients
      demonstrated developmental delay and mental retardation. Four of these patients
      are alive 23, 21, 15, and 1 year from diagnosis; one died of pneumonia with
      septicemia. Each of the four survivors has, with aging, shown hypotonia, mutism,
      contractures, and inability to function independently.

PMID- 7826850
TI  - Convulsion after blood transfusion in four beta-thalassemia intermedia patients.
AB  - Four children with beta-thalassemia intermedia ages 7 to 11 years developed a
      clinical picture characterized by headache, hypertension, convulsion, and
      cerebral hemorrhage after blood transfusion. Successive transfusions did not
      result in a similar picture. Factors responsible for this syndrome are discussed.

PMID- 7826851
TI  - Severe, acute thrombocytopenia complicating Mycoplasma infection.

PMID- 7826852
TI  - Oral megadose methylprednisolone administration in hematologic disorders.

PMID- 7826853
TI  - DNA topoisomerases as targets of therapeutics: an overview.

PMID- 7826854
TI  - Roles of DNA topoisomerases in chromosomal replication and segregation.

PMID- 7826855
TI  - Roles of DNA topoisomerases in transcription.

PMID- 7826856
TI  - DNA topoisomerase-mediated illegitimate recombination.

PMID- 7826857
TI  - Cellular regulation of mammalian DNA topoisomerases.

PMID- 7826858
TI  - Structure of eukaryotic type I DNA topoisomerase.

PMID- 7826859
TI  - Type II DNA topoisomerase genes.

PMID- 7826860
TI  - Biochemistry of bacterial type I DNA topoisomerases.

PMID- 7826861
TI  - Major advances in antibacterial quinolone therapy.

PMID- 7826862
TI  - 4-quinolones and the physiology of DNA gyrase.

PMID- 7826863
TI  - Molecular mechanisms of DNA gyrase inhibition by quinolone antibacterials.

PMID- 7826864
TI  - The biochemistry and biology of DNA gyrase.

PMID- 7826865
TI  - Mechanism of catalysis by eukaryotic DNA topoisomerase I.
AB  - The elucidation of the chemistry of the topo I reaction has provided the first
      example of how a phosphodiester bond in DNA can be temporarily broken and the
      energy for reclosure stored in a covalent linkage between the end of the broken
      strand and the enzyme (Champoux, 1977a, 1981). This type of reaction offers
      several advantages to the cell. First, unnecessary exposure of DNA ends to
      nucleolytic attack is prevented. Second, breakage and reclosure of DNA strands
      can occur without an expenditure of ATP energy. Third, the combined breakage and
      rejoining reactions can be both spatially and temporally coordinated with other
      cellular activities by regulating the activity of a single protein molecule. This
      general mechanism has not only been extended to type II topoisomerases (see
      Chapters 3 and 5), but also to the specialized single-stranded phage replication
      proteins (e.g., phi X174 gene A protein) (Ikeda et al., 1976; Eisenberg et al.,
      1977) and to site-specific recombinases such as the bacteriophage lambda
      integrase (Craig and Nash, 1983), the delta gamma and Tn3 resolvases (Reed, 1981;
      Reed and Grindley, 1981; Krasnow and Cozzarelli, 1983; Hatfull and Grindley,
      1986), and the yeast 2-microns circle FLP recombinase (Andrews et al., 1985;
      Gronostajski and Sadowski, 1985). Since the site-specific recombinases attach the
      broken strand to a different terminus rather than simply restoring the original
      phosphodiester bond as conventional topoisomerases do, they have been referred to
      as DNA strand transferases. It is conceivable that a similar mechanism applies to
      the rearrangement of immunoglobulin genes (Schatz et al., 1990) and to other
      specific genomic rearrangements that might occur during development (Matsuoka et
      al., 1991).

PMID- 7826866
TI  - The DNA binding, cleavage, and religation reactions of eukaryotic topoisomerases
      I and II.

PMID- 7826867
TI  - Preliminary results of HIV screening in sentinel facilities in Romania.
AB  - In the first months of 1994, 393 patients (random consecutive clinic attenders)
      from three sentinel clinics were tested for anti-V3 loop antibodies in ELISA with
      a branched synthetic peptide reproducing eight copies of full V3 sequence.
      Compared with a commercial HIV 1/2 ELISA kit the sensitivity of anti-V3 assay was
      97.6% and the specificity 89.7%. The seroprevalence in women attending prenatal
      clinic was 7.54% and in children with multiple hospitalization record, 3.82%.
      Both heterosexual and parenteral transmission through unsafe medical practices
      fuel actual AIDS epidemic in Romania.

PMID- 7826868
TI  - Relevance of the reactivity of HIV 1 positive sera with synthetic peptides for
      understanding antigenic differences between circulating strains.
AB  - Several problems have arisen concerning the detection methodology of sources and
      chains of HIV transmission based on molecular and antigenic relatedness of HIV
      isolates. Great progress in mapping virus genome or provirus, especially in
      identifying the changes in the env gene provides interesting data for molecular
      epidemiology. We address the same problem by the investigation of the reactivity
      of sera from HIV 1 seropositive children with two panels of synthetic peptides
      mimicking immunoreactive fragment of HIV1 glycoproteins in solid phase EIA. The
      samples proceed from two distinct settings: an orphanage in which nosocomial
      transmission was highly suspected and from different hospitals caring for HIV
      infected children. The synthetic peptides have sequences which reproduce two
      target regions: one in the principal neutralization domain of gp 120 (V3 loop)
      and the other at the COOH end of gp 41. Our results indicate that minimal
      differences in aminoacids flanking central conserved GPGRA region in V3 loop of
      gp 120 evidence strain specific antibodies while the COOH end of gp 41 reveals
      antibodies which link HIV 1 strains in a broad fashion. Sera from HIV infected
      children collected in different settings recognize the same synthetic peptides
      panel with distinct frequencies suggesting circulation of different antigenic
      strains.

PMID- 7826870
TI  - Mathematical stochastic models of some typical viral epidemiological evolutions.
AB  - The formalisms of the probability distribution and of the associated generator
      function are used to establish the equations for the first and second moments of
      the numbers of susceptible and contagious individuals. Applications are given for
      the linear cases for the epidemic evolutions, for the endemic situations and for
      virosis in course of eradication.

PMID- 7826869
TI  - Neuroophthalmological examination in children with AIDS.
AB  - Evaluation of HIV disease status includes physical examination (anthropomorphic
      measurements, neurological assessment, etc.) and laboratory examination.
      Consideration should be given to changes from baseline values, age adjusted
      normal values and the rapidity of changes. Here we compare results of
      neuroophthalmologic assessment with Western Blo (WB) profiles in cerebrospinal
      fluids (CSF) of 54 children with AIDS. Children were classified by Denver
      Developmental Screening Test (DDST) administration in encephalopathy positive (n
      = 44) and encephalopathy negative (n = 10) groups. Neuroophthalmological
      examination which included nine items with good test-retest reliability showed
      that two of them (nystagmus on following and visual memory impairment) appeared
      early in the encephalopathy free group and correlated with the loss of some gag
      band in Western Blot (lower gag score). No correlation was however, found with
      respect to p24 antigen level in cerebrospinal fluid, a marker which reflects CNS
      viral load.

PMID- 7826871
TI  - [Serological studies in man and different species of domestic animals from the
      forest-steppe region of Romania for the detection of Togaviridae and
      Bunyaviridae].

PMID- 7826872
TI  - [The action of amphiphilic drugs on human fibroblasts in vitro. Their possible
      use in antiviral and antitumor chemotherapy].
AB  - The LDH cytotoxicity test is able to emphasize the stabilisation of human embryo
      fibroblast membranes, in vitro, by two amphiphilic drugs: the metomidate and the
      thymolol. The membrane stabilisation is emphasized by the reduced LDH
      externalization as compared with the untreated cells. The use of the LDH test for
      the selection of some natural complexes or synthetic drugs with membrane
      stabilising and potential antiviral activity is proposed. The inhibition of LDH
      by metomidate was recorded, as decreasing of the enzyme activity with increasing
      metomidate concentration. This fact explains the known lactic acid accumulation,
      under metomidate treatment of human subjects. The use of metomidate in classical
      cancer treatment potentiation is proposed instead of lactate externalization
      inhibitors, already used for this aim.

PMID- 7826873
TI  - Studies regarding a fibrosarcoma induced in Sprague-Dawley rats by a murine
      cytomegalovirus. Note I. Aspects related to the character and reproduction of the
      tumor.
AB  - Through passages on Sprague-Dawley rats (performed during seven years) the serial
      transmissibility of a fibrosarcoma type tumor, with a tendency to local
      recurrence and locoregional metastasis formation, is demonstrated. The tumor was
      initially obtained by in vitro transformation of primary total rat embryonic
      cultures under the influence of a murine cytomegalovirus (M-CMV). In the course
      of passages, susceptible (S) and resistant (R) animal lines to the respective
      tumor could be obtained. The R and S crossings demonstrated the dominant
      transmission of S.

PMID- 7826874
TI  - [The epidemiological aspects of cytomegalic infection in the Banat region,
      Romania].
AB  - A survey was conducted on 711 patients, adults and children. The results
      indicated the high incidence of cytomegalovirus infection among population and
      confirmed the virus transmission through blood transfusion. The existence of
      congenital infection in newborn seems to be confirmed. Some prevention measures
      are suggested.

PMID- 7826875
TI  - Infection with human immunodeficiency viruses and human T-cell lymphotropic
      viruses in the same individuals in Nigeria.
AB  - The rate of coinfection with human immunodeficiency virus (HIV) type 1 or 2 and
      human lymphotropic virus (HTLV) type I or II was determined in Nigeria using 4153
      human sera collected from different categories of people in 21 locations in the
      country. Eight (0.2%) of samples showed evidence of mixed infection with
      different combinations of HIV-1 or 2 and HTLV-I or II. One of the eight samples
      was positive for the four human retroviruses. Patients with other sexually
      transmitted diseases and those of sexually active age groups are more likely to
      be infected with multiple human retroviruses than other categories of people
      whose sera were tested. On the other hand, there was no significant difference
      between genders. The clinical and virological implications of this finding are
      discussed.

PMID- 7826876
TI  - [Chlamydia trachomatis infection of the genitals in women].
AB  - Direct and by immunofluorescence examination of smears, conducted on 682 women
      with different diseases of the cervix uteri, allowed the detection of Chl.
      trachomatis in 10.5% and 11.1% of the subjects, respectively. The incidence of
      the infection was significantly higher among unmarried women (33.7%) than among
      married ones (4.2%). In a second group of 305 women, sexual partners of men with
      chlamydial urethritis, the incidence of infection as found by the two methods of
      diagnosis was 57.3% and 59.3%, respectively. Colposcopy showed that more than 90%
      of these women had lesions at the cervix uteri level. High frequency of
      cervicitis, associated frequently with ectopy of the cervical epithelium in the
      case of Chl. trachomatis infection, suggested the determinant implication of this
      pathogen in the inflammatory lesions of the cervix uteri. The ectopy of the
      cervix epithelium is probably a factor favoring the multiplication of the
      pathogen.

PMID- 7826877
TI  - The evidence of circulation of some viruses in a great town of Romania during the
      first half of 1992.
AB  - Complex serological survey performed in the town B. during the first half of 1992
      emphasized an active circulation of some respiratory viruses, especially of
      parainfluenza type 3 and 1, influenza subtypes A(H3N2) and A(H1N1), adeno and
      syncytial respiratory as well as of Mycoplasma pneumoniae. Less important was the
      frequence of antibodies against Chlamydia psittaci, East equine, West Nile and
      tick-borne encephalitis as well as parainfluenza type 2 and influenza type B
      viruses.

PMID- 7826878
TI  - Use of Harvard Graphics program in processing of the results obtained from
      investigations on involvement of some viruses in malignant human diseases.
AB  - Different possibilities of graphic representation of the results obtained from
      investigations on the involvement of some viruses in the malignant and
      nonmalignant human pathology are analysed. The Harvard Graphics package available
      in many IBM compatible computers was used. Owing to its several graphic options
      and access to the drawing area it was preferred to the Epi Info-program
      specialized in recording and numerical processing of epidemiology data and lesser
      in their graphic representation.

PMID- 7826879
TI  - A laboratory computer adapted for running also as a chronometer.
AB  - The program realizes the integration in the laboratory computered informational
      flow of the experiments in which determinations of the time intervals are made,
      such as cellular electrophoresis. This program consists of two components, the
      chronometer and the laboratory watch, which work independently. For the
      measurement of the time intervals, with a precision of 0.02 sec., the internal
      clock of the computer is used. Two independent time lists (S and D) can be
      controlled at the same time (alternatively). The specialized modules of the
      timing program realize the measurement and the storage of the time intervals, the
      processing (transformations and numerical processing) and the storage of the time
      intervals lists, their display and printing. With the laboratory watch one can
      set and follow five marks of time intervals, having the same origin. The commands
      are given from multiple menus and are accompanied by information under the form
      of helping texts.

PMID- 7826880
TI  - [Nucleic acid hybridization. The general principles and their application to
      virological diagnosis].

PMID- 7826881
TI  - [C-reactive protein (Crp) in different clinical forms of mumps infection].

PMID- 7826882
TI  - [Radu Portocala (1915-1993)].

PMID- 7826883
TI  - Breast cancer, present and future.

PMID- 7826884
TI  - Transfection of human estrogen receptor (ER) cDNA into ER-negative mammalian cell
      lines.
AB  - Estrogen responsiveness of breast tumors can be correlated with the presence or
      absence of the estrogen receptor (ER). Breast cancer cells that contain ER are,
      in general, responsive to stimulation by estrogen both in vivo and in vitro;
      therefore hormonal control is possible. Breast tumors that lose the ER, and
      become hormone-independent are refractory to the direct effect of estrogens and
      antiestrogens. It is therefore of interest to determine whether the re-expression
      of the ER will be sufficient to make ER-negative cells sensitive to the growth
      effect of estrogen. Transfection experiments with wild type and mutant ER cDNAs
      into different mammalian cell lines have been performed to re-establish hormonal
      control over hormone-independent cells. Paradoxically, introduction of exogenous
      ER into ER-negative cells and treatment with estrogen leads to growth inhibition
      rather than growth promotion. The activation of a number of estrogen-regulated
      genes has been examined in ER-transfectants but gene regulation is often
      variable. It is clear that the transfection of the ER gene into cells lacking
      this protein does not simply re-create the native ER-positive phenotype. Studies
      need to be extended to identify either the transcription factors that interact
      with ER to cause the negative effects of estrogen indirectly ("squelching") or
      the precise target genes that cause growth inhibition directly.

PMID- 7826885
TI  - The leucine zippers of c-fos and c-jun for progesterone receptor dimerization: A
      dominance in the A/B heterodimer.
AB  - Human progesterone receptors (hPR) exist as two isoforms: 120 kDa B-receptors
      (hPRB) and N-terminally truncated 94 kDa A-receptors (hPRA). When transfected
      separately, each isoform exhibits different transcriptional properties that are
      ligand- and promoter-specific. In human target tissues, both receptor isoforms
      are present, so that a mixture of three dimeric species, A/A, A/B, and B/B, bind
      to DNA at progesterone response elements (PRE), and regulate transcription. To
      study the transcriptional phenotype of pure A/B heterodimers uncontaminated by
      A/A or B/B homodimers, we exploited the property of the leucine zipper (zip)
      domains of fos and jun, to form pure heterodimers. Chimeric constructs were made
      linking the zip of either c-fos or c-jun to the C-terminus of hPRB or hPRA (hPR
      zip) to produce A-fos, B-fos, A-jun or B-jun. To determine whether the A- or B
      isoform is functionally dominant in the A/B heterodimer, cells expressing hPR-zip
      chimeras were treated with the progestin antagonist RU486, which produces
      opposite transcriptional effects with the two isoforms. Gel mobility shift and
      immune co-precipitation assays show that in the presence of RU486 only pure
      heterodimers form between A-fos/B-jun or A-jun/B-fos, and bind DNA at PREs. Thus,
      in these pairs, interactions between the extrinsic fos/jun zipper domains
      override interactions between the intrinsic hPR dimerization domains. We find
      that under these conditions, antagonist-occupied B-zip homodimers stimulate
      transcription, while antagonist-occupied A-zip homodimers are inhibitory, and
      that pure A/B zip heterodimers have the inhibitory transcriptional phenotype of
      the A-zip homodimers. We conclude that, in pure heterodimers, A-receptors are
      dominant negative inhibitors of B-receptors. Additionally, the pure PR-zip
      heterodimers, unlike wild-type receptors, bind a PRE in the absence of hormone
      but do not activate transcription. Thus, PR dimerization and PRE binding are
      necessary but, without hormone, not sufficient to activate transcription.

PMID- 7826886
TI  - The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on estrogen metabolism in MCF
      7 breast cancer cells: evidence for induction of a novel 17 beta-estradiol 4
      hydroxylase.
AB  - Rates of microsomal 17 beta-estradiol (E2) hydroxylation at the C-2, -4, -6
      alpha, and -15 alpha positions are each induced greater than 10-fold by treating
      MCF-7 breast cancer cells with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The
      TCDD-induced activities at the C-2, -6 alpha and -15 alpha positions have been
      attributed to cytochrome P450 1A1 (CYP1A1); however, the low Km 4-hydroxylase
      induced by TCDD appears to be a distinct enzyme. We report here that antibodies
      to cytochrome P450-EF (mouse CYP1B1) selectivity inhibited the C-4 hydroxylation
      of E2 catalyzed by microsomes from TCDD-treated MCF-7 cells. Western blots probed
      with anti-CYP1B antibodies showed the induction of a 52 kDa microsomal protein in
      response to treatment with TCDD in MCF-7 cells. Western blots of microsomes from
      HepG2 cells did not show the TCDD-induced 52 kDa protein, and microsomes from
      TCDD-treated HepG2 cells did not catalyze a low Km hydroxylation of E2 at C-4.
      Cellular metabolism experiments also showed induction of both the C-2 and -4
      hydroxylation pathways in TCDD-treated MCF-7 cells as evidenced by elevated 2-
      and 4-methoxyestradiol (MeOE2) formation. In contrast, TCDD-treated HepG2 cells
      showed 2-MeOE2 formation predominantly over 4-MeOE2. Northern blots of RNA
      isolated from untreated and TCDD-treated cells, when probed with the human CYP1B1
      cDNA, showed induction of a 5.2 kb RNA in MCF-7 cells but not in HepG2 cells in
      response to treatment with TCDD. These results provide additional evidence for
      the induction by TCDD of a novel E2 4-hydroxylase in MCF-7 cells but not in HepG2
      cells and indicate possible endocrine regulatory roles for the newly discovered
      group of enzymes of the CYP1B subfamily.

PMID- 7826887
TI  - The androgen receptor mRNA is up-regulated by testosterone in both the Harderian
      gland and thumb pad of the frog, Rana esculenta.
AB  - Alpha 32P-labelled cDNA probe from plasmid containing rat androgen receptor (rAR)
      has been tested in hybridization experiments using RNAs from the Harderian gland
      and thumb pad of the edible frog, Rana esculenta. Northern blot analysis has
      shown a high degree of homology between the rAR cDNA and the frog androgen
      receptor mRNA (fAR mRNA); this has been supported by both the hybridization
      conditions (high stringency) and the molecular size of fAR mRNA which is quite
      similar to those described in mammals (9.4 kb). The role of androgens has been
      further investigated with respect to the kinetics of expression of fAR mRNA in in
      vivo experiments. In both the Harderian gland and thumb pad, testosterone has
      increased the levels of fAR mRNA as compared with the untreated groups. The use
      of cyproterone acetate (CPA) in combination with testosterone has resulted in a
      loss of the increase in fAR mRNA as compared to testosterone-treated groups,
      while CPA alone has resembled the control group. In primary cultures of frog
      Harderian gland and thumb pad cells, the steady-state levels of fAR mRNA have
      been increased in the cells exposed to testosterone as compared to those not
      exposed. These findings confirm that, in these androgen target tissues,
      testosterone exerts an up-regulation on its own receptors, increasing the
      accumulation of fAR mRNA in the same way as oestrogens up-regulate the expression
      of their own receptors in Xenopus liver and oviduct cells.

PMID- 7826888
TI  - Immunofluorescence of mineralocorticoid receptors in peripheral lymphocytes:
      presence of receptor-like activity in patients with the autosomal dominant form
      of pseudohypoaldosteronism, and its absence in the recessive form.
AB  - Pseudohypoaldosteronism is a syndrome characterized by salt wasting and a failure
      to thrive due to the resistance towards the action of aldosterone. Aldosterone
      levels and plasma renin activity are extremely elevated and aldosterone binding
      sites in peripheral mononuclear leukocytes have regularly shown to be reduced or
      absent. Sporadic as well as familial cases have been identified and an autosomal
      dominant as well as an autosomal recessive mode of inheritance has been
      described. A defect in the aldosterone receptor has been postulated, however,
      molecular genetic analysis in selected patients has not revealed a mutation in
      the sequence of the coding region of the cDNA of the mineralocorticoid receptor
      gene. In the present study we have used a fluorescence-labeled antibody to detect
      possible receptor expression in monocytes from patients with various clinical
      forms of pseudohypoaldosteronism. Patients with the sporadic as well as with the
      autosomal dominant form were clearly immunopositive despite being negative in
      terms of aldosterone receptor binding. In contrast in two patients with the
      autosomal recessive form there was no detectable receptor protein, consistent
      with the results obtained in the aldosterone binding studies. These results
      suggest that the pathogenesis of pseudohypoaldosteronism is heterogeneous not
      only regarding the mode of inheritance but also in terms of receptor binding.
      Thus, in a subgroup of patients the inability of the receptor to bind ligand may
      be due to a defect involving other, probably cellular factors rather than a
      deficiency or a defect in the mineralocorticoid receptor system itself.

PMID- 7826889
TI  - Lack of evidence for estrogen and progesterone receptors in human adipose tissue.
AB  - We have previously presented data indicating the absence of estrogen and
      progesterone receptors from human adipose tissue by the use of specific
      antibodies (Abbott) as well as specific ligands. In addition, specific estrogen
      and progesterone cRNA probes did not hybridize to any mRNA species in either
      abdominal or gluteal/femoral adipose tissue as demonstrated by solution
      hybridization and Northern blot. In order to demonstrate even extremely small
      quantities of gene products we have now used the Polymerase chain reaction
      technique to study estrogen- and progesterone receptor gene expression. Sequences
      corresponding to each specific cDNA were demonstrated indicating small amounts of
      estrogen- and progesterone receptor mRNA not detected by RNA/RNA or RNA/TNA
      (total nucleic acids) hybridization assays. The estrogen receptor-regulated gene
      pS2, however, was not induced by estrogens in human adipose tissue in contrast to
      a significant increase in pS2 mRNA levels after estrogen exposure to the estrogen
      receptor(+) cell line MCF7. From these results we conclude that estrogen- and
      progesterone receptors are absent from human adipose tissue and that the
      extremely low level of transcription of the corresponding genes is not sufficient
      to allow translation of the message into functional proteins.

PMID- 7826890
TI  - Regulation of cytochrome P450scc synthesis and activity in the ovine corpus
      luteum.
AB  - The rate-limiting step in luteal biosynthesis of progesterone consists of
      cleavage of the side chain of cholesterol by mitochondrial cytochrome P450 side
      chain cleavage enzyme (P450scc) to form pregnenolone. Luteal mRNA encoding
      P450scc, quantitated on selected days of the 16-day ovine estrous cycle, was
      similar on days 3 and 6, increased by 2-fold on day 9 (P < 0.05) and remained
      elevated on day 15. Levels of P450scc mRNA on day 15 of pregnancy were not
      different from those found on any day of the cycle (P < 0.05). To determine
      whether levels of mRNA encoding P450scc are hormonally regulated, ewes on day 10
      of the estrous cycle were injected with hCG or prostaglandin F2 alpha (PGF2
      alpha). P450scc mRNA was not increased for up to 36 h after injection of hCG, nor
      decreased within 8 h after injection of PGF2 alpha (P < 0.05). An assay for
      P450scc activity was developed which utilized ovine small and large luteal cells
      in the presence of 22R-hydroxycholesterol and ovine high density lipoprotein.
      Enzyme activity was quantitated by measurement of progesterone production. In
      small luteal cells activation of the protein kinase A (PKA) second-messenger
      system by treatment with LH resulted in 910% increase in progesterone production
      without altering activity of P450scc. Activation of the protein kinase C (PKC)
      second-messenger system with phorbol 12-myristate 13-acetate caused a 51%
      reduction in progesterone secretion from large luteal cells but did not alter
      activity of P450scc. These findings suggest that in mature luteal tissue steady
      state levels of mRNA encoding P450scc, and enzyme activity are independent of
      acute regulation by activation of PKA or PKC second-messenger systems.

PMID- 7826891
TI  - Nanomolar concentrations of untransformed glucocorticoid receptor in nuclei of
      intact cells.
AB  - The subcellular distribution of untransformed glucocorticoid-receptor complex in
      vivo has been studied by chemical crosslinking of intact cells, and using a
      procedure adequate for correction of experimental errors due to redistribution of
      components between cytosolic and nuclear fractions. We found that in HeLa S3
      cells 85.4% of total glucocorticoid-receptor complexes are located in nuclei, and
      14.6% are cytosolic. If measurements were performed with MCF-7 cells, we
      determined that the nuclear pool of glucocorticoid-receptor complexes accounts
      for 75.2% of the total cellular content, whereas the remaining 24.8% are
      cytosolic. When the subcellular distribution of estrogen-receptor complexes was
      determined, instead, we found that they are almost exclusively located in nuclei
      of MCF-7 cells, which contain 88.9% of the total. In order to estimate the molar
      concentration of receptors in cytosol and nuclei of intact cells, we determined
      the free water content of the two compartments. The volume of solvent was found
      to vary in the three cell lines we have studied, and our data showed that these
      variations are due to the cytosolic fractions, as the free water content of
      nuclei is essentially the same in those cells. When the free water content and
      the levels of glucocorticoid-receptor complexes we have measured were used to
      estimate the molar concentrations of receptors, we found that these range between
      0.4 and 18.9 nM in cytosols, and between 3.9 and 6.3 nM in nuclei of the three
      cell lines we have studied. We then concluded that the relative distribution of
      untransformed glucocorticoid-receptor complexes between cytosol and nuclei is
      cell-specific but their molar concentration in the nuclear compartment does not
      greatly vary among different cells.

PMID- 7826892
TI  - Increasing progesterone secretion and 3 beta-hydroxysteroid dehydrogenase
      activity of human cumulus cells and granulosa-lutein cells concurrent with
      successful fertilization of the corresponding oocyte.
AB  - In many studies it has been documented that the induction of multiple follicular
      growth in humans results in an asynchrony between the degree of cumulus
      mucification, oocyte meiotic maturation, fertilizability, and follicular cell
      progesterone (P4) secretion. The present study was carried out on oocytes
      enclosed in fully mucified cumulus. Thus, oocyte fertilizability was correlated
      to human cumulus cell (hCC) and human granulosa-lutein (G-L) cell competence for
      P4 secretion in culture. In the G-L cells, P4 secretion and percentage of cells
      manifesting 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) activity increased
      concurrently with the period of culture. In the hCC, however, P4 secretion
      decreased concurrently with elongation of the culture period, whereas the
      percentage of 3 beta-HSD-positive cells increased. In hCC corresponding to the
      fertilized oocytes, P4 accumulation in culture medium was 1.9-fold (P < 0.001)
      and 1.6-fold (P < 0.02) higher on days 0-3 and 3-5 of culture, respectively, as
      compared to P4 accumulation in hCC of unfertilized oocytes. Also, in hCC
      corresponding to the fertilized oocytes, the degree of 3 beta-HSD activity was
      found to be significantly higher shortly after aspiration and after either 3 or 5
      days, compared to hCC of unfertilized oocytes. In the G-L cells pooled from all
      follicles yielding mature cumulus-oocyte complexes, P4 accumulation and
      percentage of 3 beta-HSD-positive cells increased concurrently with the increase
      in percentage of fertilized eggs of each individual woman. These results indicate
      that in stimulated cycles, follicles yielding mature cumulus-oocyte complex,
      oocyte fertilizability, and G-L cell or hCC competence for P4 secretion are
      correlated and synchronous.

PMID- 7826893
TI  - Gemfibrozil treatment is associated with elevated adrenal androgen,
      androstanediol glucuronide and cortisol levels in dyslipidemic men.
AB  - We have investigated the role of steroid hormones as coronary risk factors in the
      Helsinki Heart Study population of dyslipidemic middle-aged men. We compare here
      the effects of gemfibrozil and placebo on the serum levels of
      dehydroepiandrosterone (DHEA), its sulfate (DHEAS), their metabolite
      androstanediol glucuronide (3 alpha-AdiolG), androstenedione, cortisol,
      testosterone, and sex-hormone binding globulin (SHBG) in non-smokers. We also
      examined the associations between steroid and lipoprotein levels in both
      treatment groups. Compared with placebo gemfibrozil treatment was associated with
      significant elevations of the mean levels of DHEA 10.2 vs 8.0 nmol/l; P < 0.005,
      of DHEAS 8.0 vs 5.8 mumol/l; P < 0.001, of 3 alpha AdiolG 18.3 vs 8.4 nmol/l; P <
      0.001, of androstenedione 5.7 vs 5.1 nmol/l; P < 0.02, and of cortisol 426 vs 358
      nmol/l; P < 0.001. The mean SHBG levels decreased from 46.4 to 41.7 nmol/l; P =
      0.03 with gemfibrozil treatment. No difference was found in testosterone levels
      17.7 vs 18.8 nmol/l; P = 0.11, or the ratio of testosterone/SHBG 0.45 vs 0.43; P
      = 0.23. Positive correlations were found between high density lipoprotein
      cholesterol and DHEAS (r = 0.267; P < 0.01) and DHEA (r = 0.282; P < 0.01) levels
      and negative correlations between low density lipoprotein-cholesterol and 3 alpha
      AdiolG (r = -0.400; P < 0.001) and cortisol (r = -0.281; P < 0.01) levels in the
      gemfibrozil group. Our results indicate that gemfibrozil treatment increases the
      production and turnover of adrenal androgens and cortisol, and suggest that
      activation of the adrenocortical function and increased metabolism of androgens
      are related to the improved lipoprotein pattern during gemfibrozil treatment.

PMID- 7826894
TI  - Amniotic fluid 17-hydroxyprogesterone in early pregnancy.
AB  - The results of measurement of 17-hydroxyprogesterone (17-OH-P) in 125 samples of
      amniotic fluid (AF) from early amniocenteses are presented. The fetuses from all
      pregnancies studied were unaffected by congenital adrenal hyperphasia caused by
      21-hydroxylase deficiency. The AF 17-OH-P level increases slightly but
      significantly between the 11th and 15th week of gestation, with a maximum in the
      14th week. There is no difference between the values measured in male and female
      fetuses. The AF 17-OH-P levels from the early gestation were compared with those
      from the 16th-22nd week of pregnancy (published previously). The overall
      differences of AF 17-OH-P concentrations when considered in all gestational age
      groups in the whole period 12-22 weeks were statistically insignificant. Thus,
      the biochemical prenatal diagnosis of congenital adrenal hyperplasia due to 21
      hydroxylase deficiency and control of its early fetal treatment could be carried
      out starting from the end of the first trimester in the same way as at the later
      period of gestation.

PMID- 7826895
TI  - Binding of sex steroid binding protein to plasma membranes of human testis.
AB  - The existence of a specific binding site for sex steroid binding protein (SBP or
      SHBG) was detected on plasma membranes prepared from the testis of a patient
      affected by a variant form of testicular feminization. A binding technique using
      [125I]SBP as a tracer allowed us to identify a single set of binding sites,
      characterized by a Kd of 1.917 x 10(-11) M. The maximum number of binding sites
      was 5.2 fmol/mg membrane protein. Membranes were also prepared from a sample of
      genital skin from the same patient, but no binding for [125I]SBP was detectable.
      The evidence of the SBP membrane receptor in the testis of a patient affected by
      Morris syndrome extends our knowledge about the tissue distribution of the SBP
      receptor and suggests the possible implication of SBP and its recognition system
      in a disorder related to peripheral androgen insensitivity.

PMID- 7826897
TI  - "We're not just readouts of our genes": Harvard professor criticizes Human Genome
      Project.

PMID- 7826896
TI  - Cancer services in England and Wales: a restructuration is needed.

PMID- 7826898
TI  - Do we know the treatment of choice for hairy cell leukemia?

PMID- 7826899
TI  - Involvement of DNA topoisomerases and DNA topoisomerase inhibitors in the
      induction of leukemia cell differentiation.

PMID- 7826900
TI  - Recent progress in B- and T-cell lymphomas.
AB  - The data we review indicate substantial progress in understanding of the biology
      of T- and B-cell lymphomas in humans. They indicate how processes central to
      normal development of B- and T-cells are corrupted in lymphomas and how these
      abnormalities may be approached or reversed in the context of therapy. Recent
      progress in treating lymphomas is less striking. The key issues here are whether
      more intensive therapy is better, whether some persons can be cured with less
      intensive therapies and whether immune therapies will prove useful. We hope to
      address these at the next B and T-cell lymphoma meeting scheduled for 1996.

PMID- 7826901
TI  - Immunoconjugates: lessons from animal models.
AB  - Monoclonal antibody-mediated cancer therapy has evolved through a challenging
      chain of problems and solutions. The very limited therapeutic success obtained
      with unarmed monoclonal antibodies has increased the interest in different
      antibody-based targeting strategies, and numerous preclinical and even clinical
      studies with immunoconjugates have now been conducted. We comment here on the
      messages implicit in a recent report on a doxorubicin-anti-carcinoma antibody
      conjugate and from several other studies.

PMID- 7826902
TI  - Drug immunotargeting for carcinomas: a reality at last?

PMID- 7826903
TI  - A dose intensity study of FLAC (5-fluorouracil, leucovorin, doxorubicin,
      cyclophosphamide) chemotherapy and Escherichia coli-derived granulocyte
      macrophage colony-stimulating factor (GM-CSF) in advanced breast cancer patients.
AB  - BACKGROUND: It has been demonstrated that granulocyte-macrophage colony
      stimulating factor (GM-CSF) can ameliorate chemotherapy-induced neutropenia. The
      extent to which GM-CSF can increase the actual delivered dose intensity of
      combination chemotherapy over multiple cycles of therapy to patients with
      advanced breast cancer has not been well defined. We conducted a phase I/II study
      of dose-intensive FLAC chemotherapy (5-fluorouracil, leucovorin, doxorubicin,
      cyclophosphamide) in combination with GM-CSF in patients with locally advanced
      and metastatic breast cancer to study the acute and cumulative toxicities, anti
      tumor activity and dose-intensity achievable with this regimen. METHODS: Eighty
      one patients with newly diagnosed stages IIB, III and IV breast cancer who were
      previously untreated with chemotherapy and who had measurable disease received
      multiple cycles of FLAC chemotherapy plus E. coli-derived GM-CSF administered
      every three weeks. RESULTS: FLAC plus GM-CSF as associated with significant
      cumulative hematologic toxicity. Ninety-eight percent of patients developed grade
      4 neutropenia; 29% of all cycles administered required hospitalization for fever
      and neutropenia; 41% and 22% of cycles required red blood cell and platelet
      transfusions, respectively. Other significant toxicities with E. coli-derived GM
      CSF included mild to moderate first dose effects (hypotension, dyspnea, abdominal
      cramping) in 30% of patients; late occurring anaphylactoid reactions in 11% of
      patients; and vascular thromboses. The average delivered dose intensities over
      all cycles were cyclophosphamide, 210 mg/m2/week; doxorubicin, 14.8 mg/m2/week
      and 5-fluorouracil, 342 mg/m2/week. The overall clinical response rates were 100%
      and 83% for LABC and metastatic patients, respectively. There were 23% (6/26)
      pathologic CR's in the LABC patients given neoadjuvant FLAC and 22% (12/54)
      clinical CR's in the stage IV patients. The median survival of the LABC patients
      has not been reached (> 26 months) and is 30 months for the stage IV patients.
      CONCLUSIONS: The administration of multiple cycles of FLAC plus E. coli-derived
      GM-CSF therapy is associated with cumulative, dose-limiting myelosuppression,
      especially thrombocytopenia, as well as significant clinical toxicity. A modest
      increase in FLAC dose intensity over the starting doses was achievable with the
      addition of GM-CSF. FLAC chemotherapy has substantial antitumor activity in the
      treatment of advanced breast cancer. The potential usefulness of FLAC plus GM-CSF
      must be balanced by its considerable cost and alteration in patients' quality of
      life due to toxicity. Combination hematopoietic growth factor strategies may be
      able to reduce the toxicity of FLAC and to allow further increase dose intensity.

PMID- 7826904
TI  - The International (Ludwig) Breast Cancer Study Group Trials I-IV: 15 years follow
      up.
AB  - BACKGROUND: Adjuvant systemic therapy prolongs disease-free and overall survival
      in both pre- and postmenopausal patients. Available data shown benefit from multi
      agent chemotherapy, prolonged tamoxifen treatment, and ovarian ablation, and that
      the combination of chemo- and endocrine therapy might be advantageous. In 1978
      the International (Ludwig) Breast Cancer Study Group (IBCSG) initiated four
      complementary randomized controlled clinical trials to evaluate the roles of
      chemo-endocrine combinations or endocrine therapy alone in specific populations
      defined by risk (for pre- and perimenopausal patients) or by age (for
      postmenopausal patients). The results at 10 and 13 years' median follow-up for
      these trials are summarized in this report and are compared to those of the
      Overview meta-analysis with regard to chemo-endocrine or endocrine therapy
      combinations. Furthermore, types of first relapses by sites and second malignant
      diseases are reported. PATIENTS AND METHODS: 1601 evaluable patients with node
      positive disease were included into the studies I-IV. In Trial I (491
      premenopausal patients with 1-3 positive axillary nodes) we studied the addition
      of low-dose continuous prednisone (p) to a cyclophosphamide-methotrexate
      fluorouracil (CMF) combination. In Trial II 327 premenopausal patients with four
      or more positive axillary nodes were randomized to one year CMFp or to a surgical
      oophorectomy followed by CMFp. In Trial III (463 postmenopausal patients 65 years
      old or younger), combined chemoendocrine therapy (one year of CMFp plus tamoxifen
      (T)) was compared to endocrine therapy (1 year of p + T) or to surgery alone. In
      Trial IV 320 postmenopausal patients 66 to 80 years old were treated either by
      surgery alone or by surgery followed by 1 year prednisone and tamoxifen. RESULTS:
      In Trial I the addition of prednisone allowed a higher dose of cytotoxics to be
      administered compared with CMF alone. Despite this increased dose intensity, 13
      year disease-free survival (DFS) and overall survival (OS) were similar for the
      two treatment groups (49% vs. 52% DFS, 59% vs. 65% OS for CMFp vs. CMF). In Trial
      II the addition of surgical oophorectomy to CMFp yielded an improved outcome
      which approached statistical significance for the subset of 107 patients known to
      have estrogen receptor-positive tumors (DFS, 23% vs. 15%, p = 0.13; OS, 41% vs.
      30%, p = 0.12). In Trial III combined chemoendocrine therapy improved DFS and OS
      compared with endocrine therapy alone (p + T) given for the same duration, or no
      adjuvant treatment (DFS, 35% vs. 25% vs. 14%, p < 0.0001; OS, 48% vs. 36% vs.
      32%, p = 0.01). In Trial IV p + T improved DFS compared with no adjuvant therapy
      (27% vs. 15%, p = 0.004). Despite competing risks for this elderly population, OS
      was also improved but the result was not statistically significant (34% vs. 22%,
      p = 0.08). CONCLUSIONS: The overall results of these four trials indicate that
      the continuation of investigations on combined chemo-endocrine therapies is
      warranted. The prognosis of the patients, all node-positive, treated with the
      most effective adjuvant treatment is such that there is a large potential for
      improvement.

PMID- 7826905
TI  - Long-term results of alpha interferon as initial therapy and splenectomy as
      consolidation therapy in patients with hairy cell leukemia. Final report from the
      Italian Cooperative Group for HCL.
AB  - PURPOSE: In 1987 the Italian Cooperative Group for the Study of hairy cell
      leukemia (HCL) started a prospective trial with the following three major aims:
      1) to confirm the effectiveness of alpha-IFN as first-line treatment; 2) to
      assess the usefulness of splenectomy as consolidation treatment in patients
      achieving a satisfactory partial remission (PR) with alpha-IFN, and 3) to explore
      whether splenectomy in patients achieving complete remission (CR) with alpha-IFN
      can reduce the risk of relapse after discontinuation of the drug. PATIENTS AND
      METHODS: One-hundred seventy-seven patients with histologically-confirmed HCL
      were registered in the HCL88-A trial between December 1987 and January 1992.
      Inclusion criteria included no previous treatment and age less than 66 years. All
      patients received total doses of 3 MU of alpha-IFN daily for 12 months except for
      those who achieved early CR and would stop treatment after 6 or 9 months.
      Patients could be treated with different alpha-IFNs. At the time of the present
      analysis, 166 patients (93.8%) were fully evaluable. RESULTS: Treatment of HCL
      patients with alpha-IFN at the onset of the disease resulted in 28 CR (16.9%),
      103 PR (62.0%), and 27 Minor Remissions (MR) (16.3%). Patients treated with
      different alpha-IFNs achieved similar results: the overall response rate (CR + PR
      + MR) was 92.7%, 97.2%, and 95.3% for patients treated with r-alpha-2a, r-alpha
      2b, and alpha-N1, respectively. The presence of a leukemic phase and a poor
      performance status were associated with a statistically significant lower
      response rate. Patients who were randomly assigned and underwent splenectomy
      after achieving a PR had a better but not significant 4-year progression-free
      survival than cases randomized for observation (53% vs. 22%, p = 0.116). Overall,
      5 patients died after study entry, with an actuarial 5-year survival rate of 96%
      for the entire group of 166 patients. After a mean follow-up time of 38 months,
      only one second malignancy has been recorded. CONCLUSIONS: Initial therapy with
      alpha-IFN, regardless of the type of alpha-IFN used, induces satisfactory
      responses in the majority of patients with HCL, but in most instances
      discontinuation of treatment results in recurrence of disease. In most cases
      alpha-IFN improves the performance status of patients and favors a satisfactory
      bone marrow recovery and thus could still play a role in the initial management
      of the disease. Although splenectomy following alpha-IFN could prolong the
      progression free survival, its use should be restricted to selected cases.

PMID- 7826906
TI  - Biochemical modulation of 'classical' multidrug resistance by BIBW22BS, a potent
      derivative of dipyridamole.
AB  - BACKGROUND: Modulators of the 'classical' multidrug resistance (mdr) phenotype
      have low efficacy in patients with solid tumors. We analyzed BIBW22BS, 4-[N-(2
      hydroxy-2-met- hyl-propyl)-ethanolamino]-2,7-bis(cis-2,6-dimethyl-morpho- lino)-6
      phenylpteridine, a derivative of dipyridamole, for its higher potential to
      modulate mdr. MATERIALS AND METHODS: Four human malignant cell lines: BRO, A2780,
      GLC4, SW1573, the Pgp-positive sublines: BRO/mdr1.1, 2780AD and the non-Pgp
      sublines: GLC4/ADR, SW1573/2R120 were used in vitro to investigate BIBW22BS as a
      modulator of the antiproliferative effects of vincristine and doxorubicin and to
      compare the potency of BIBW22BS with that of dipyridamole, verapamil, bepridil
      and flunarizine. BRO/mdr1.1 s.c. well-established xenografts in nude mice were
      used to study the modulating properties of BIBW22BS 50 mg/kg i.v. followed after
      one h by vincristine 1 mg/kg i.p. or doxorubicin 8 mg/kg i.p. weekly x 2.
      RESULTS: BIBW22BS was 20- to 100-fold more potent than dipyridamole in the
      reversal of resistance in the Pgp-positive sublines. Reversal of resistance was
      obtained in a dose-dependent manner and was complete at concentrations of 0.5-2.5
      microM. At non-toxic, equimolar concentrations of 1.0 microM BIBW22BS showed
      higher modulating potency than the calcium-channel blockers. BIBW22BS did not
      affect resistance in the non-Pgp sublines. BRO/mdr1.1 s.c. xenografts have stable
      multidrug-resistance characteristics upon serial transplantation. BIBW22BS,
      vincristine, or doxorubicin as single agents were not effective in vivo, while
      the addition of BIBW22BS could significantly reduce the tumor growth expressed as
      the T/C% of vincristine from 109% to 48% and that of doxorubicin from 55% to 32%.
      However, reversal of vincristine resistance in BRO/mdr1.1 xenografts was not
      complete when compared to the efficacy of vincristine in BRO xenografts.
      CONCLUSION: The results encourage the further preclinical development of BIBW22BS
      as a modulator of 'classical' multidrug resistance in cancer patients.

PMID- 7826907
TI  - Biochemotherapy with thymosin alpha 1, interleukin-2 and dacarbazine in patients
      with metastatic melanoma: clinical and immunological effects.
AB  - BACKGROUND: DTIC and interleukin-2 (IL-2), as single agents, have a limited anti
      tumor activity in patients with metastatic melanoma. Experimentally, thymosin
      alpha 1 (TA1) may modulate the action of IL-2. We investigated the clinical and
      immunological effects of a combination with these three agents. PATIENTS AND
      METHODS: Forty-six patients with measurable metastatic melanoma were treated with
      DTIC 850 mg IV on day 1, TA1 2 mg s.c. on days 4 to 7, and IL-2 18 MU/m2/d by
      continuous intravenous infusion on days 8 to 12. Cycles were repeated every 3
      weeks. RESULTS: Objective responses were obtained in 15 (36%) of 42 evaluable
      patients (CI at 95%: 22%-50%). Two patients experienced complete responses, and
      stable disease was observed in five. The median time to progression was 5.5
      months and median survival was 11 months. Side effects were predominantly caused
      by IL-2. Treatment was tolerated reasonably well, and there was no overlapping
      toxicity or interference between chemotherapy and biotherapy. Baseline sCD4
      levels seem to correlate to tumor burden. Patients benefiting from treatment had
      lower sCD4 and higher sCD8 than did progressing patients. CONCLUSIONS: The
      combination of DTIC + TA1 + IL-2 is active in the treatment of advanced melanoma,
      with acceptable toxicity. However, even more active regimens are needed, and the
      interactions between thymic hormones and cytokines should be further explored.

PMID- 7826908
TI  - Incidence, mortality and survival from invasive cervical cancer in Vaud,
      Switzerland, 1974-1991.
AB  - BACKGROUND: Several factors have contributed to the substantial decline in
      mortality from cervical cancer registered in most areas of the world, i.e.,
      improved sexual hygiene, changes in reproductive factors, cervical screening,
      and, possibly, improved treatment. Each of these components is evaluated through
      a systematic inspection of trends in incidence, mortality and survival rates
      registered for a well-defined population. PATIENTS AND METHODS: Trends in
      incidence, mortality and survival from invasive cervical cancer over the period
      1974-1991 were analysed for three separate age groups (< 55, 55-64, > or = 65
      years), histological type and stage using data from the Cancer Registry of the
      Swiss Canton of Vaud. RESULTS: Below age 55, the age-standardized (world
      standard) incidence rate was 9.3/100,000 women in 1974-76, it declined steadily
      thereafter down to 2.9 in 1986-88, but increased to 4.3 in 1989-91. In the age
      group 55-64, cervical cancer incidence remained around 40/100,000 to the end of
      the 1970s, but thereafter declined to 10.9 in 1989-91. No consistent trend was
      observed in elderly women, and the rate in 1989-91 (26.7/100,000) was similar to
      that in 1974-76 (33.7). The overall age-standardized cervical cancer incidence
      declined from 13.5/100,000 in 1974-76 to 5.8 in 1986-88, but rose to 6.4 in 1989
      91. A similar pattern was observed for mortality, with a fall in rates in younger
      women between 1974 and 1985 (from 2.1 to 0.6/100,000), and a subsequent rise to
      1.1/100,000 in 1989-91. A substantial decline in mortality was observed in women
      aged 55 to 64 since the early 1980's, from 17.2 in 1980-82 to 3.3 in 1989-91. No
      clear mortality trend was evident in older women. Overall, cervical cancer
      mortality declined from 4.3/100,000 in 1974-76 to 2.3 in 1989-91. The five-year
      relative survival rates were around 0.70-0.75 for younger women, around 0.60 for
      those aged 55 to 64, and 0.50 for elderly ones. In a Cox proportional hazard
      model, age and clinical stage were significantly related to survival, but not
      histological type and calendar period of diagnosis. No substantial change in
      survival from invasive cervical cancer was observed over the 18-year period
      considered, nor was there any notable change in the stage distribution over time.
      The proportion of adenocarcinomas, however, appears to have increased in the most
      recent calendar period. CONCLUSIONS: These data reflect the impact of screening
      on cervical cancer rates, which, however, appeared restricted to women below age
      65. An upward trend in cervical cancer incidence and mortality rates for younger
      women was also apparent, and there was no indication from these data of an
      improved survival for invasive cervical cancer patients over the last two
      decades. Extention of screening to elderly women appears to be a priority for
      reducing cervical cancer rates in this population.

PMID- 7826909
TI  - Primary therapy of multiple myeloma with paclitaxel (taxol).
AB  - BACKGROUND: The treatment of multiple myeloma remains unsatisfactory and new
      active agents are needed. Paclitaxel is effective against a variety of solid
      tumors and we assessed the utility against multiple myeloma. PATIENTS AND
      METHODS: From March 1993 to May 1994, we treated 33 patients with newly diagnosed
      multiple myeloma with paclitaxel given intravenously at a dose of 125 mg/m2 over
      24 hours (13 patients) or at a dose of 135 mg/m2 over 3 hours (20 patients).
      RESULTS: Five of 33 patients responded (15%; 95% CI: 5 to 32%) with an
      unmaintained remission of 3-11+ months. Severe but reversible neutropenia was the
      major dose limiting toxicity, but myalgias and alopecia were also common.
      CONCLUSION: Paclitaxel was slightly active against multiple myeloma. Whether
      higher doses or new analogues of this agent can produce superior results requires
      further study.

PMID- 7826910
TI  - Oral doxifluridine in elderly patients with metastatic colorectal cancer: a
      multicenter phase II study.
AB  - BACKGROUND: Cancer chemotherapy in elderly patients is an important and under
      researched area. Doxifluridine is a fluoropyrimidine derivative and is activated
      to 5-fluorouracil by uridine phosphorylase, which is more highly expressed in
      malignant cells. Because of the high bioavailability and low toxicity of oral
      doxifluridine we conducted this phase II trial to evaluate the feasibility,
      toxicity and activity of a home therapy with oral doxifluridine in elderly
      metastatic colorectal cancer patients. PATIENTS AND METHODS: Forty-three elderly
      metastatic colorectal cancer patients entered the study: their median ECOG
      performance status was 1 (0-2) and median age 74 years (69-83), the predominant
      site of metastasis was liver and all but one of the patients had received no
      previous chemotherapy. Doxifluridine was given orally at the initial daily total
      dose of 2250 mg for 4 consecutive days every week. The daily dose was reduced to
      1500 mg if toxicities greater than grade 2 (WHO) occurred. RESULTS: Forty-two
      patients are evaluable for toxicity: treatment was well tolerated, with the most
      common side effect being diarrhea, severe in 7 (17%) patients (6 grade 3 and 1
      grade 4). Thirty-six patients are evaluable for response and 2 complete and 3
      partial responses have been observed (response rate 14%; 95% confidence limit
      interval 5%-29%). CONCLUSIONS: This study demonstrates that a home therapy with
      oral doxifluridine in elderly advanced colorectal cancer patients is feasible,
      with a relatively low rate of toxicity, and has moderate activity, comparable to
      that of intravenous 5-fluorouracil. Therefore, this treatment may be considered
      for the management of advanced colorectal cancer in the elderly.

PMID- 7826911
TI  - Chemotherapy with dacarbazine and 5-fluorouracil in advanced medullary thyroid
      cancer.
AB  - BACKGROUND: Experience with chemotherapeutic agents in the management of advanced
      medullary thyroid carcinoma (MTC) is limited and controversial. However, since
      MTC is a neuroendocrine neoplasm, we considered the possibility that cytotoxic
      drugs previously used in the treatment of these tumours could also have activity
      in MTC. PATIENTS AND METHODS: Five patients (4 females and 1 male, aged 22-71
      years) with locally advanced or metastatic MTC received 5 day intravenous courses
      of dacarbazine (DTIC) (250 mg/sqm) and 12 hour infusion 5-fluorouracil (450
      mg/sqm), given every 4 weeks. Six cycles were administered to 4 patients and four
      to 1 patient. RESULTS: Three partial responses lasting 9, 10+ and 8+ months were
      observed; one patient had stable disease and one progressive disease. Toxicity
      was acceptable with grade I thrombocytopenia and grade II leukopenia occurring in
      one patient, and grade II nausea and vomiting in four patients. CONCLUSIONS: In
      our experience, treatment of advanced thyroid carcinoma with DTIC and 5-FU
      appeared to have significant activity and was well tolerated.

PMID- 7826912
TI  - Phase II trial of 10-EDAM in advanced soft tissue sarcoma. A study of the
      Canadian Sarcoma Group and the National Cancer Institute of Canada Clinical
      Trials Group.
AB  - BACKGROUND: Inoperable locally recurrent soft tissue sarcomas (STS) are incurable
      with chemotherapy. Therefore the National Cancer Institute of Canada Clinical
      Trials Group are performing phase II studies in an attempt to find better drugs.
      PATIENTS AND METHODS: Thirty-one evaluable patients with incurable soft tissue
      sarcoma were treated with the antifol 10-EDAM at a dose of 80 mg per m2/week.
      RESULTS: Mucositis was the most common toxicity. Only 41% of patients received >
      or = 90% of the planned dose time because of dose modification mainly for grade 1
      mucositis. Two patients died after neutropenic episodes. Toxicity otherwise was
      generally mild (< grade 2). One patient had a pathologically confirmed complete
      response but relapsed after four months. Another had a partial response lasting
      16 weeks. Eleven other patients had stabilization of disease. CONCLUSIONS: In
      this study, 10-EDAM was not found to be an effective agent to treat advanced soft
      tissue sarcoma.

PMID- 7826913
TI  - Minoxidil (Mx) as a prophylaxis of doxorubicin--induced alopecia.
AB  - BACKGROUND: Minoxidil (Mx) is known to induce hair growth in men with male
      pattern baldness. Based on this potential, the effectiveness of Mx 2% topical
      solution was evaluated in cancer patients (pts) to prevent doxorubicin-induced
      alopecia. PATIENTS AND METHODS: 48 female pts with different types of solid
      tumors treated with doxorubicin-based chemotherapy in a dose range of 50-60
      mg/m2/cycle were randomly assigned to receive Mx 2% topical solution or placebo.
      RESULTS: 88% and 92% of pts in both arms showed severe alopecia (p = ns). No
      adverse effects were observed. CONCLUSION: In this study Mx 2% topical solution
      was non-toxic but was not effective in the prevention of chemotherapy-induced
      alopecia.

PMID- 7826914
TI  - Priming low-dose chest radiotherapy followed by chemotherapy for limited small
      cell lung cancer.

PMID- 7826915
TI  - Two new cases of hyperpyrimidinuria associated with excessive 5-fluorouracil
      toxicity.

PMID- 7826916
TI  - How does the message of cancer specialists affect routine medical practice? Only
      sixty percent of surgical adjuvant breast cancer treatment is based on hormone
      receptor status.

PMID- 7826917
TI  - Adjuvant treatment for cancer of the colon and rectum.

PMID- 7826918
TI  - ARCON.

PMID- 7826919
TI  - Who should follow up cancer patients? Nurse specialist based outpatient care and
      the introduction of a phone clinic system.
AB  - The objective of this study was to pilot and evaluate a nurse based follow-up
      system for oncology patients in terms of feasibility and impact on outpatient
      oncology practice. We identified clinical situations with a defined range of
      clinical problems, which were set out on a proforma (Appendix) for a nurse
      consultation. Following a period of training, surveillance during radiotherapy
      was transferred to a nurse 'on treatment clinic' and a defined point of post
      treatment follow-up to a nurse 'phone clinic'. The effectiveness of the nurse
      based follow-up was assessed by a prospective analysis of the consultation
      records. The impact on clinical practice was assessed in the form of audit of the
      clinic work-load before and after introduction of the nurse follow-up service.
      The patient assessment by the nurse specialist was satisfactory and covered the
      range of problems encountered. Medical referral by the nurse specialist was
      necessary in 3/33 on treatment assessments and 1/61 phone appointments. The
      medical outpatient work-load was estimated to decrease by 30%. Structured follow
      up by a skilled and trained nurse specialist provides excellent support and
      effective medical surveillance in defined situations in oncology follow-up.
      Patients appeared satisfied with the arrangement and the pilot study suggested up
      to 30% reduction in the medical outpatient work-load. The use of 'phone clinics'
      offers an effective alternative to the conventional outpatient clinic model,
      while being less costly and more convenient for patients and staff.

PMID- 7826920
TI  - An audit of Hickman catheter use in patients with solid tumours.
AB  - The purpose of this study was to analyse the use and relative complication rates
      of Hickman lines inserted by angiographic and surgical routes in patients with
      solid tumours. Sixty-one patients (median age 55 years; range 21-81) with solid
      tumours had 71 Hickman catheters inserted. Fifty-three patients had 58 catheters
      inserted angiographically and eight patients had 13 catheters inserted
      surgically. Indications were as follows: for administration of infusional
      chemotherapy (48 patients), poor venous access (nine patients), needle phobia
      (four patients). The catheters remained in situ for 7981 days (median 105; range
      10-750). Immediate complications occurred only in angiographically placed
      catheters (ten pneumothoraces, one tachydysrhythmia). Pneumothorax was associated
      with poor nutritional status but not with age, side of insertion or catheter
      gauge. The median body mass indices (BMIs) were 19.65 kg/m2 and 22.8 kg/m2 in
      those with and without pneumothorax respectively (P = 0.0045). Five of six
      patients with BMI < 19 kg/m2 developed a pneumothorax, compared with five of 52
      with BMI > 19 kg/m2 (P = 0.0003). The overall sepsis rate was 2.38 per 1000
      catheter days. Systemic sepsis was significantly increased for surgically
      inserted lines (3.94 versus 0.60 per 1000 catheter days; P = 0.001), although
      there was no significant difference in superficial sepsis (2.36 versus 1.04 per
      1000 catheter days; P = 0.22). We conclude that Hickman catheters provide safe,
      long-term venous access in patients with solid tumours. Angiographic insertion
      carries a greater risk of acute complications in patients of poor nutritional
      status but a significantly lower risk of late systemic infective
      complications.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7826921
TI  - The prevalence of menopausal symptoms in patients treated for breast cancer.
AB  - A survey has been performed to discover the prevalence of menopausal symptoms in
      108 patients successfully treated for breast cancer. Patients were assessed by
      them answering a custom designed questionnaire, and the use of the Hospital
      Anxiety and Depression (HAD) scale and the Greene Climacteric Scale. During the
      first year after treatment 70% of women suffered such symptoms; overall 60% of
      women surveyed were affected. Adjuvant hormonal treatment was the largest
      contributing factor in the development of symptoms. There was a relationship with
      borderline cases of anxiety, but not with definite cases of anxiety, as measured
      by the HAD scale. The high proportion of women shown to be affected means that
      treatment of menopausal symptoms should be incorporated into randomized trials of
      adjuvant therapy.

PMID- 7826922
TI  - The significance of MALT histology in thyroid lymphoma: a review of patients from
      the BNLI and Royal Marsden Hospital.
AB  - Data from a series of 45 patients with Stage I and II non-Hodgkin's lymphoma
      (NHL) of the thyroid gland were analysed retrospectively to determine the
      incidence and prognostic significance of histopathological features of tumour
      origin from mucosa associated lymphoid tissue (MALT). The overall 5- and 10-year
      cause specific survival from NHL for the series was 79%. Evidence of tumour
      origin from MALT was the only significant prognostic factor for overall survival
      identified by multivariate analysis of the series (P < 0.01). A total of 31 (69%)
      tumours showed such evidence, the cause specific patient survival from NHL at 5
      and 10 years being 90% compared with only 55% at 5 years for the 14 patients
      without such evidence. For patients given initial treatment with radiotherapy
      alone, those with evidence of tumour origin from MALT had a relatively low
      relapse rate and a relatively high success rate from salvage therapy, compared
      with a relatively high relapse rate and negligible success from salvage therapy
      in those without evidence of such tumour origin.

PMID- 7826923
TI  - Malignant inverted papillomas: a review of seven cases and implications for
      treatment.
AB  - Seven cases of inverted papilloma with malignant change, of the nasal cavity and
      paranasal sinuses, were referred to the department of radiotherapy in Newcastle
      between 1979 and 1990. All patients received postoperative radiotherapy, which,
      in three, prevented further recurrence; in the remaining four, locally recurrent
      disease proved resistant to both radiotherapy and chemotherapy, ultimately
      becoming fatal. Only one of seven patients developed cervical lymph node
      metastases. Postoperative radiotherapy is of value in about 40% of patients. It
      is most useful when only microscopic residual disease is seen. Radiotherapy and
      chemotherapy, when used for bulky macroscopic disease, were of no value.

PMID- 7826924
TI  - Conformation therapy using a computer controlled telecobalt unit for advanced
      cervical carcinoma.
AB  - This retrospective analysis evaluates the results of conformation radiotherapy
      for patients with advanced cervical carcinoma. Between January 1980 and September
      1987, 16 patients with high common iliac/para-aortic node metastases from
      advanced carcinoma of the uterine cervix were treated using conformation
      radiotherapy. A large area from L1/L2 to the pelvis, with an average length of 23
      cm, was treated to a total tumour dose of 5000-5500 cGy, with a daily tumour dose
      of 180-200 cGy in 28-30 daily fractions, using a computer controlled tracking
      cobalt unit (CCTCU). Before external beam irradiation, 11 patients underwent
      laparotomy/hysterectomy, seven were given chemotherapy and eight received
      brachytherapy. The preliminary results are encouraging. The actuarial 1-year, 3
      year and 5-year survival rates after treatment were 81%, 44% and 37%,
      respectively. The locoregional control rate was 62.5%. None of the patients
      relapsed in the para-aortic nodes. All patients tolerated the large area of
      tracking irradiation therapy very well. None had any severe acute or delayed
      radiation complications. Use of the conformation radiotherapy technique to
      include the pelvic and para-aortic nodes has been shown to be an effective form
      of radiotherapy with minimal morbidity.

PMID- 7826925
TI  - Waiting times for radiotherapy treatment: not all that mysterious and certainly
      preventable.
AB  - A computer program which deals specifically with the analysis and prediction of
      waiting times for radiotherapy has been written for a standard spreadsheet. The
      model has several components. The basic module calculates waiting times on the
      basis of any mismatch between the number of patients referred for treatment each
      week and the number of patients who can actually start treatment in that week.
      Monte Carlo simulations are used to estimate the 95% confidence intervals on
      projected waiting times. Another module calculates projected waiting times for
      three different categories of treatment, given user specified parameters,
      including financial data. The trade-offs between financial profit and waiting
      times for treatment are demonstrated. This shows quite explicitly the human
      consequences (in terms of delay in starting treatment) of decreasing, for fiscal
      reasons, resources allocated to certain categories of patients. The advantage of
      this type of analysis is that it clearly shows that waiting lists do not always
      arise through mismanagement of resources, they arise because resources are
      inadequate.

PMID- 7826926
TI  - Carcinoma of the lung.

PMID- 7826927
TI  - Adjuvant therapy of early stage carcinoma of the cervix.

PMID- 7826928
TI  - Current issues in the non-surgical management of primary vulvar squamous cell
      carcinoma.

PMID- 7826929
TI  - Metastatic chordoma: pattern of spread and response to chemotherapy.
AB  - Chordoma is a rare slow growing tumour arising from elements of the primitive
      foetal notochord. We report a case of widespread dissemination to lung, liver and
      bone following radical primary treatment.

PMID- 7826930
TI  - Rupture of the thoracic duct following treatment of mediastinal seminoma.
AB  - Chylothorax is a rare condition that may occur as a complication of malignancy.
      There is only one prior report of chylothorax complicating metastatic testicular
      seminoma. We report a further patient in which the development of the chylothorax
      occurred a result of a favourable response to chemotherapy.

PMID- 7826931
TI  - Malignant change in a mediastinal dermoid cyst.
AB  - Mature benign cystic teratomas, or dermoid cysts, usually arise in the ovary.
      They can, however, occur at other sites, including the mediastinum. Malignant
      change within dermoid cysts is a rare but recognized complication, occurring in
      1%-2% of cases. A case of malignant change within a mediastinal dermoid cyst
      occurring 19 years after initial presentation is described.

PMID- 7826932
TI  - Women's fear of crime and abuse in college and university dating relationships.
AB  - Several government-sponsored victimization surveys have found women's fear of
      crime to be much higher than that of men even though their probability of being
      victimized is much lower than men's. On the basis of these results, several
      criminologists contend that women's fear is subjectively based. However,
      government surveys have not adequately examined the consequences of the physical,
      sexual, and psychological abuse of women by male intimates. Feminist researchers
      contend that these assaults greatly contribute to a generalized fear of crime
      that is objectively based. Using data from a national survey on female abuse in
      Canadian college/university dating relationships, this study tested and failed to
      support the feminist hypothesis that violence by male intimates results in higher
      levels of fear. However, an examination of an ex post facto hypothesis assessing
      the relationship between fear in private places (the home) and abuse by male
      dating partners found positive correlations. Women who had been psychologically
      or sexually victimized by male dating partners felt more insecure in their own
      homes than other women. These increased feelings of fear were linked to
      experiences of sexual coercion, unwanted sexual touching, psychological abuse,
      and sexual abuse. The results suggest that women reassess their feelings of fear
      when victimized by male intimates. In particular, places generally viewed as safe
      by women, their own homes, are seen as more threatening than they had been in the
      past.

PMID- 7826933
TI  - Structural and cultural determinants of child homicide: a cross-national
      analysis.
AB  - Models of structural characteristics that may influence national infant and child
      homicide victim rates are derived from prior research. Expected effects of
      structural characteristics from a "social control" perspective are compared with
      expected effects from a "guardians, suitable target" perspective. Gartner's
      (1991) claim that structural factors influence victim rates only in nations with
      low social insurance expenditures is also evaluated. Statistical analysis of
      three infant and child age groups with homicide rates from 1965-1969, 1970
      1974...1985-1988 fails to support the claim that high and low social insurance
      expenditure strata differ. Further, no independent effects of Gartner's (1991)
      three measures of family structure are found. Indicators of family
      stress/resources, female status, the culture of violence, and a proxy for
      unmeasured variables and measurement error all contribute to produce high levels
      of explained variance in each age group.

PMID- 7826934
TI  - Posttraumatic stress symptom profiles of battered women: a comparison of
      survivors in two settings.
AB  - This study sought to develop a profile of posttraumatic stress symptoms
      experienced by battered women and to explore differences among subsamples. Two
      groups of survivors from five states were compared: 159 who had obtained help at
      domestic violence programs (DVP) and 33 who had obtained help at other types of
      programs (NDVP). They completed three self-report measures of posttraumatic
      stress and a fear questionnaire. Sixty percent of the women in the DVP group and
      62% in the NDVP group met criteria for a diagnosis of posttraumatic stress
      disorder (PTSD). The most common symptoms were: nightmares intrusive memories of
      the abuse, avoiding reminders of it, and hyperarousal, and nightmares. DVP women
      experienced a variety of symptoms more frequently. Group differences in PTSD
      symptomatology were not present after statistically controlling for severity and
      frequency of the violence and length of time since the abusive relationship.

PMID- 7826935
TI  - Reliability and diagnostic efficacy of parents' reports regarding children's
      exposure to marital aggression.
AB  - Mothers, fathers, and 8- to 11-year-old children from 181 two-parent families
      independently reported on the occurrence of husband-to-wife physical aggression
      and wife-to-husband physical aggression; parents additionally indicated whether
      the child had been witness to the aggression. First this study examined
      interspousal agreement regarding whether parents have been physically aggressive
      toward one another and whether the child has witnessed interparental physical
      aggression. There was moderate agreement between parents as to the occurrence of
      physical aggression and only fair agreement as to whether the child saw or heard
      the aggression. Second, this study explored the diagnosticity of a joint parent
      report as an indicator of child exposure to marital aggression. Receiver
      operating characteristic (ROC) curves are presented separately for husbands' and
      wives' aggression, indicating the explicit trade-off between true positives
      (sensitivity) and false positives (one minus specificity) in using the joint
      parent report as a diagnostic indicator. Standard ROC analysis suggests that the
      joint parent report is equally diagnostic in predicting children's reports of
      exposure to husbands' and wives' aggression. Finally, decisions regarding how to
      use parent reports as an indicator of children's exposure to marital aggression
      are discussed as depending on the base rate of child reports of exposure and the
      objective sought in classifying children and/or families.

PMID- 7826936
TI  - Physical, sexual, and emotional abuse by male intimates: experiences of women in
      Japan.
AB  - This article examines the nature of violence (physical, emotional, and sexual)
      perpetrated by Japanese men against their female intimates. Data were collected
      in a nationwide mail questionnaire survey with a convenience sample of 796 women
      between July and December, 1992. Most respondents were currently married and
      working full-time; average age was 43.5 years. Over three fourths reported at
      least one type of violence perpetrated by their male intimate partner. These
      Japanese women reported a wide range of abuse--from a slap to an assault with a
      deadly weapon, from verbal ridicules to restriction of social activities, and
      from incompliance with contraception to forced, violent sex. About two thirds of
      the most serious physically violent incidents resulted in injury. Sociocultural
      factors unique to Japanese women's experiences of male violence are identified
      and discussed along with their implications for prevention and intervention.

PMID- 7826937
TI  - Civil protection orders: a viable justice system tool for deterring domestic
      violence.
AB  - The prevalence and severity of domestic violence have illuminated the need for
      effective justice system responses to this pernicious phenomenon. A remedy that
      all states now provide is the civil protection order, but the forms of relief
      available, duration of orders, and processes for obtaining them vary from state
      to state. Examples of types of relief include prohibitions against further abuse
      and contact with the protected person; eviction from the residence; and temporary
      custody of children. Studies of civil protection orders suggest that they can be
      an effective form of relief if the justice system takes affirmative steps to
      increase their power, including screening petitioners to identify those who need
      more elaborate safety plans; provision of specific and comprehensive orders and
      low cost and effective service of them; stringent enforcement of orders by law
      enforcement and the court; and linkages from the court to advocacy services,
      shelters, legal representation, and other services.

PMID- 7826938
TI  - Truncation of the A alpha chain of MHC class II molecules results in inefficient
      antigen presentation to antigen-specific T cells.
AB  - Antigen presenting cells (APC) expressing MHC class II molecules composed of
      chains with part or all of the cytoplasmic domains deleted are inefficient at
      presenting hen egg lysozyme peptides to antigen specific T cell hybrids compared
      with APC that express wild-type MHC class II molecules. This effect is most
      apparent for mutants in which the alpha chain has been truncated. The
      inefficiency in antigen presentation can be amplified by pulsing the APC for 4 h
      with peptide rather than having peptide present throughout the presentation
      assay. Fixation of antigen-pulsed APC improves the capacity of APC with truncated
      class II molecules to stimulate T cell hybrids. Fixation of APC prior to exposure
      to antigen also leads to significant improvement in antigen presentation by the
      truncated class II molecules. Because the inefficiency of a given hybrid for
      antigen presentation does not correlate with its ability to transduce a signal as
      measured by protein kinase C translocation, we suggest that defects in this
      pathway are not the only cause of impaired antigen presentation. However, because
      previous studies have demonstrated the need for an intact cytoskeleton for
      successful antigen presentation, we propose that the carboxy truncated class II
      molecules are inefficient in antigen presentation because they are unable to
      generate the signal that ultimately leads to their interaction with the
      cytoskeleton. These observations underscore the complexity of the events that are
      required for achieving effective interactions between MHC class II molecules and
      TCR, and suggest, with regard to efficient antigen presentation, that the
      physical state of the class II molecules is at least as important as their signal
      transducing capacity.

PMID- 7826939
TI  - Requirement of a second signal from antigen presenting cells in the clonal
      deletion of immature T cells.
AB  - The role of antigen presenting cells (APC) in T cell clonal deletion was
      investigated by culturing murine thymic lymphocytes with the superantigen
      staphylococcal enterotoxin B (SEB) in the absence or presence of APC. As the APC,
      we used B lymphoma cell lines A20.2J and BAL17.2, both expressing MHC class II
      antigens at high levels. SEB reactive V beta 8+ cells were deleted only when
      A20.2J cells were used as APC. By using thymocytes from transgenic mice carrying
      a TCR beta chain transgene, it was further shown that the deletion occurred at
      the CD4+CD8+ stage. The other cell line, BAL17.2, failed to induce clonal
      deletion, although this cell line was able to stimulate the proliferative
      response of SEB-primed T cells. The activity of A20.2J cells to induce clonal
      deletion was completely abolished by fixation with paraformaldehyde, whereas the
      same treatment kept the ability of this cell line to induce the proliferative
      response of non-primed as well as SEB-primed T cells. It was further shown that
      the deletion was abolished by the addition of anti-MHC class II but not anti-B7
      mAb in the culture. These results provided explicit evidence that a signal(s)
      from APC, which is distinct from that required for primary or secondary
      proliferative response of mature peripheral T cells, is involved in clonal
      deletion of thymic immature T cells.

PMID- 7826940
TI  - Multiple nuclear factors bind to novel positive and negative regulatory elements
      upstream of the human MHC class I gene HLA-A11.
AB  - Quantitative expression of class I genes varies widely in different tissues,
      during development and in some neoplastic cells. Regulatory DNA sequences
      controlling levels of transcription of class I genes have been characterized in
      the murine and swine promoters. Although some regulatory features appear to be
      retained in humans, most of them are not evolutionary conserved. In this study,
      we identify novel DNA sequences and factors which contribute to the regulation of
      the human HLA-A11 gene. Two activator elements (-155 to -91 and -335 to -206) and
      one negative element (-172 to -156), distinct from those previously described are
      mapped within 335 bp upstream of exon 1 of the human HLA-A11 gene. Various
      nuclear factors bind to these regulatory elements, some of which are cell
      restricted or interact with evolutionary divergent regulatory sequences of the
      human class I gene promoter. Two of the five DNA-binding sites characterized in
      this work bind at least two proteins which compete for the occupancy of their
      site. The identification of these new regulatory elements provides a more
      comprehensive basis for the understanding of physiological or pathological
      modulation of MHC class I transcription in humans.

PMID- 7826941
TI  - Influence of human leukocyte antigen genes on TCR V gene segment frequencies.
AB  - Human leukocyte antigen (HLA)-dependent selection mechanisms exerted during
      thymic maturation are supposed to be main contributing factors to the genetic
      predetermination of the TCR repertoire and may have a detectable effect on adult
      peripheral blood lymphocyte V segment frequencies. Here, we analyzed whether
      polymorphic or non-polymorphic HLA determinants are associated with selected
      expression of some V gene segment specificities. We first examined the reactivity
      of 17 V segment specific mAb on purified CD4+ and CD8+ cell fractions in 10
      unrelated people. We found a significant overexpression of only three V segment
      products (V beta 2, V beta 5.1 and V beta 6.7) in CD4+ and none in CD8+ cell
      fractions in most individuals. Skewing of certain V beta segments by non
      polymorphic HLA determinants (i.e. class II for CD4+ and class I for CD8+ cells)
      is therefore more limited (3/17) than previously thought. Considering the effects
      of polymorphic HLA determinants, we compared TCR V segment frequencies in HLA
      identical siblings to sibling pairs who differ at one or both HLA haplotypes,
      using 13 V beta specific mAb. In pairwise comparisons, we found that the HLA
      complex had no detectable effect on TCR repertoire in five large families with
      multiple siblings. Together, these observations suggest that HLA-predicted
      selection mechanisms exerted during thymic maturation might not have a
      predominant influence shaping the TCR repertoire of normal adults.

PMID- 7826942
TI  - Entry of CD4-CD8- immature thymocytes into the CD4/CD8 developmental pathway is
      controlled by tyrosine kinase signals that can be provided through TCR
      components.
AB  - Entry of thymus-migrated precursor cells into the CD4/CD8 developmental pathway
      was analyzed by using the short-term organ cultures of day 14 fetal mouse thymus
      lobes. Organ cultures of CD4-CD8- day 14 fetal thymocytes for 1-2 days resulted
      in the generation of CD4-CD8+ cells, which were mostly immediate precursor cells
      for CD4+CD8+ thymocytes. This differentiation of CD4-CD8- thymocytes into CD4
      CD8+ cells was strongly enhanced by anti-CD3 antibodies. The anti-CD3- induced
      generation of CD4-CD8+ cells was even found in the immunodeficient scid fetal
      thymus cultures, and the cell surface CD3 expression on the scid fetal thymocytes
      could be directly visualized, indicating that functional CD3 could be expressed
      on CD4-CD8- immature thymocytes without being associated with rearranged TCR
      components. The anti-CD3-induced generation of CD4-CD8+ cells from scid and
      normal fetal thymus cultures was inhibited by tyrosine kinase inhibitors
      Herbimycin A and Tyrphostin. The generation of CD4-CD8+ cells in unstimulated
      normal fetal thymus cultures was also markedly inhibited by the tyrosine kinase
      inhibitors but not by Cyclosporin A, suggesting that tyrosine kinase-dependent
      but calcineurin-independent signals were essential for the differentiation of CD4
      CD8- thymocytes. Interestingly, the generation of CD4-CD8+ cells from the normal
      fetal thymus cultures was modestly but consistently enhanced by anti-TCR beta
      antibody, suggesting that functional TCR beta in addition to CD3 was expressed on
      normal CD4-CD8- immature thymocytes. On the other hand, anti-TCR delta antibody
      did not affect this differentiation in the normal fetal thymus cultures and the
      generation of CD4-CD8+ cells from the fetal thymus cultures of TCR delta
      deficient mice was still enhanced by anti-TCR beta or anti-CD3 antibodies,
      indicating that either TCR delta chains or TCR delta+ cells were not involved in
      the control of the differentiation into CD4-CD8+ cells. These results indicate
      that the entry of CD4-CD8- immature thymocytes into the CD4/CD8 developmental
      pathway is controlled by tyrosine kinase signals and that these signals can be
      provided through the engagement of TCR-CD3 complexes with or without TCR beta
      chains expressed on the CD4-CD8- immature thymocytes.

PMID- 7826943
TI  - Regulation of IL-3 receptor expression: evidence for a post-transcriptional
      mechanism that dominantly suppresses the expression of beta subunits.
AB  - The IL-3 receptor (IL-3R) is composed of alpha and beta subunits. Two homologous
      beta subunits of IL-3R are present in the mouse: AIC2A is the IL-3 specific beta
      subunit, and AIC2B is the common beta subunit shared by IL-3, IL-5 and
      granulocyte macrophage colony stimulating (GM-CSF) factor receptors. Both beta
      subunits form functionally indistinguishable high-affinity IL-3Rs with the same
      IL-3R specific alpha subunit (IL-3R alpha or SUT-1). Cell surface expression of
      the alpha and beta subunits of IL-3R was found to be diminished in an IL-3 non
      responsive variant (MC/9.IL-4) derived from an IL-3-dependent mast cell line,
      MC/9. This IL-3R-defective phenotype was dominant based on cell fusion
      experiments. Moreover, regulatory mechanisms of the alpha and beta subunits are
      distinct since cell hybrids between MC/9.IL-4 and a CTLL-2 transfectant (CTLL/AS)
      expressing AIC2A and IL-3R alpha showed a significantly reduced expression of the
      AIC2A mRNA, while the IL-3R alpha expression was unchanged. Since transcription
      of both AIC2A and IL-3R alpha cDNAs in the CTLL/AS was driven by an artificial
      promoter, SR alpha, and nuclear run-off assays showed similar transcriptional
      rates of the AIC2A gene in both CTLL/AS and the cell hybrids between MC/9.IL-4
      and CTLL/AS, the dominant suppression of the beta subunits is post
      transcriptional and sequence-specific. A target sequence of the negative
      regulator must be present within 2756 bases of AIC2A mRNA, which is transcribed
      from the transfected cDNA in CTLL/AS cells. Similar dominant suppression of the
      beta subunit expression was also found in a B cell line WEHI231. As the negative
      regulator suppresses expression of the beta subunits of IL-3, IL-5 and GM-CSF
      receptors, it has the potential to eliminate all three high-affinity receptors
      simultaneously.

PMID- 7826944
TI  - Intravenous injection of irradiated Leishmania major into susceptible BALB/c
      mice: immunization or protective tolerance.
AB  - It is well established that BALB/c mice can be protected from fatal infection
      with Leishmania major by prophylactic intravenous (i.v.) immunization with
      irradiated parasites. Protection is critically dependent on the route of
      injection with i.v. injection being protective and subcutaneous injection not
      protective. We used this BALB/c-L. major model system to investigate this
      phenomenon. We analyzed quantitatively the parasite-specific, CD4+ T cell
      mediated immune responses by limiting dilution. Subcutaneous vaccination resulted
      in priming of CD4+ precursor T cells, whereas i.v. vaccination was ineffectual.
      Moreover, i.v. injection prevented the increase in the number of specific
      precursor cells induced by infection of normal mice during the first weeks post
      challenge with virulent parasites. We show here that this was not due to the
      elimination of the virulent challenge parasites as a result of immunity nor to
      inefficient antigen presentation of the irradiated organisms after i.v.
      injection. The data presented here suggest that i.v. injection results in
      tolerization rather than immunization. Tolerization as a mechanism of host
      protection is consistent with earlier observations that transient
      immunosuppression results in cure of L. major infection in BALB/c mice. Transfer
      of antigen presenting cells (APC) isolated from spleens of mice injected
      previously with irradiated parasites mimicked to some extent the effect of i.v.
      immunization with irradiated parasites. The possible involvement of these APC in
      decreasing the parasite-specific T cell response is discussed.

PMID- 7826945
TI  - Age-dependent changes in the response to staphylococcal enterotoxin B.
AB  - In the present study we investigated the response of old mice to staphylococcal
      enterotoxin B (SEB) immunization. Old mice were susceptible to lethal toxic
      shock, probably mediated by tumor necrosis factor-alpha, although lethal toxic
      shock was not observed in young mice. Old mice were able to produce more IL-2 and
      IL-4 than young mice in response to in vivo immunization with SEB. V beta 8+CD4+
      T cells of old mice expanded less in vivo and were not deleted in response to
      SEB. However, in spite of the absence of clonal deletion, SEB was found to induce
      energy of SEB reactive cells in old mice, as demonstrated by reduced in vitro T
      cell proliferation to SEB and reduced in vitro IL-2 and IL-4 production.

PMID- 7826946
TI  - Role of the CDR1 region of the TCR beta chain in the binding to purified MHC
      peptide complex.
AB  - Single alanine substitutions were introduced into the CDR1 region of the beta
      chain of a Kd-restricted TCR. Mutants and wild-type TCR were attached to the zeta
      chain of the CD3 complex and expressed at the surface of a rat basophil cell
      line. Transfectants were tested for the binding of purified soluble Kd-peptide
      complexes. With this experimental system, accessory molecules are unlikely to
      play a major role and the contribution of each residue to the interaction can be
      addressed. Results show that all positions in the CDR1 region are involved in the
      binding to the Kd-peptide complex but at varying degrees. These effects are
      discussed in relation to a molecular model of the TCR. Comparison of these
      results with previous data obtained in a T cell hybridoma system suggests the
      existence of a threshold in the TCR affinity necessary for mature T cell
      activation.

PMID- 7826947
TI  - Human Fas ligand: gene structure, chromosomal location and species specificity.
AB  - Fas ligand (FasL) is a 40 kDa type II membrane protein belonging to the tumor
      necrosis factor family, which induces apoptosis by binding to its receptor, Fas.
      In this report, we isolated the chromosomal gene for human FasL. The human FasL
      gene consists of approximately 8.0 kb and is split into four exons. The human
      FasL gene was mapped on chromosome 1q23 by in situ hybridization against human
      metaphase chromosomes. Human FasL cDNA was isolated by the reverse polymerase
      chain reaction of mRNA prepared from human activated peripheral blood
      lymphocytes. Human FasL is a type II membrane protein consisting of 281 amino
      acids with a calculated M(r) of 31,759. It has an identity of 76.9% at the amino
      acid sequence level with mouse FasL. Both human and mouse recombinant FasL
      expressed in COS induced apoptosis in the cells expressing either human Fas or
      mouse Fas, indicating that FasL fully cross-reacts between human and mouse. A
      comparison of human and mouse FasL chromosomal genes indicated that a
      approximately 300 bp sequence upstream of the ATG initiation codon is highly
      conserved between them. Several transcription cis-regulatory elements such as SP
      1, NF-kappa B and IRF-1 were recognized in this region.

PMID- 7826948
TI  - Inhibition of alloreactivity by mAb MR6: differential effects on IL-2- and IL-4-
      producing human T cells.
AB  - mAb MR6 has previously been shown to block both IL-4-induced T cell proliferation
      and IL-4-dependent IgE production, suggesting a functional association between
      the antigen detected by MR6 (gp200-MR6) and the human IL-4 receptor. In this
      study the potential modulatory effects of mAb MR6 on IL-4 function have been
      further analysed in alloantigen-specific assays for cytotoxic and Th cell
      maturation, mature cytotoxic T cell killing, helper cell proliferation, and
      generation of IL-2- and IL-4-producing Th cells in a mixed lymphocyte reaction
      (MLR). Our data show that mAb MR6 has an inhibitory effect on both clonal
      expansion and maturation of cytotoxic T lymphocyte precursors within the
      alloreactive T cell population. mAb MR6 had no effect on the maturation of Th
      lymphocyte precursors (assayed by IL-2 production). However, this mAb had
      striking differential effects on cytokine production in MLR cultures, showing
      total ablation of IL-4 but no alteration of IL-2 levels in the supernatant
      medium. The absence of IL-4 from culture supernatants could be due to the fact
      that mAb MR6 is blocking cytokine production, that it is speeding up IL-4
      internalization and utilization or that it inhibits the expansion of the T cell
      subset(s) that secretes IL-4. The data demonstrate that the action of mAb MR6 is
      focused on the IL-4-producing population and raise the possibility that gp200-MR6
      may play an important role in this aspect of IL-4 function.

PMID- 7826949
TI  - Tolerance induction by elimination of subsets of self-reactive thymocytes.
AB  - Immature thymocytes expressing TCRs which confer reactivity to self-MHC molecules
      are subject to efficient elimination as a result of negative selection.
      Previously, we have identified a lineage of H-2Kb Tg mice, CD2Kb-3, which fails
      to reject skin grafts from mice expressing H-2Kb even though H-2Kb-specific
      cytotoxic T cells can be generated in vitro. We now show that bone marrow derived
      cells are responsible for tolerance induction and that tolerance is acquired, at
      least in part, by negative selection in CD2Kb-3 mice. Thymocytes expressing two
      different transgenic TCR (TCR-Tg) clonotypes conferring reactivity to H-2Kb are
      eliminated prior to the CD8+CD4+ stage of differentiation in double Tg (CD2Kb-3 x
      TCR-Tg)F1 mice. As in other cases where thymocytes from TCR-Tg mice develop in
      the presence of deleting ligands, large numbers of TCR+ CD8-CD4- T cells
      accumulate in double Tg mice. However, these T cells fail to respond to H-2Kb in
      vitro but can be activated with immobilized anti-clonotypic antibody.
      Consequently, thymocytes expressing these types of TCR molecules represent a
      fraction of H-2Kb-reactive thymocytes which are unable to mature into T cells
      capable of mounting H-2Kb-specific cytotoxic responses. Presumably, precursors of
      H-2Kb-specific cytotoxic T cells found in the periphery of CD2Kb-3 mice express a
      distinct repertoire of TCR molecules conferring reactivity to H-2Kb. We consider
      potential explanations to account for this discrepancy and their wider
      implications, including the possibility that the repertoire of thymocytes able to
      recognize self-H-2Kb molecules in CD2Kb-3 mice is divided into distinct subsets;
      those which are, and those which are not, subject to negative selection.

PMID- 7826950
TI  - Maintenance of clonal anergy by endogenously produced IL-10.
AB  - Inadequate co-stimulation of tumor reactive T cells may contribute to the fact
      that antigenic tumors are not normally rejected by the immune system. We recently
      reported that the induction of profound unresponsiveness in a T cell clone by
      melanoma cells expressing MHC class II antigens may provide a mechanism for these
      tumor cells to escape immunosurveillance. Here we demonstrate that two T cell
      clones (sTC3 and sTS5) produced high amounts of IL-10 after being rendered
      anergic by autologous melanoma cells. Co-culture of these T cell clones with
      melanoma cell transfectants expressing B7, which failed to induce anergy,
      resulted in a significantly lower production of IL-10. IL-10 production by the
      anergic T cell clones correlated with an impaired ability to produce IL-2 in
      response to TCR mediated activation. Neutralization of IL-10 reduced the duration
      of T cell unresponsiveness from 14 to only 4 days, but inhibition of IL-10
      production during initiation of anergy showed no effect on it. Induction of the
      unresponsive state, as well as the subsequent IL-10 production in sTC3 cells,
      could be prevented by the addition of cyclosporin A to the primary co-culture of
      sTC3 and the autologous melanoma. Taken together, these results indicate that IL
      10 is important for maintenance of T cell anergy induced by contact with
      nonprofessional antigen presenting cells such as MHC class II+ melanoma cells.
      Furthermore, we were able to detect IL-10 in serum from melanoma patients and IL
      10 mRNA in tumor infiltrating lymphocytes isolated from melanoma metastases,
      suggesting an in vivo relevance of our in vitro findings.

PMID- 7826951
TI  - Analysis by in situ hybridization of cytokine mRNA expression in the murine
      developing thymus.
AB  - We have used in situ hybridization to investigate the expression of IL-1, IL-2,
      IL-4, IL-6 and IFN-gamma genes by thymic cells during fetal development in mice.
      Two waves of mRNAs were detected in thymic cells for IL-1 at days 16 and 19 of
      gestation, for IL-2 at days 14 and 18, and for IL-4 at days 14 and 16. Three
      peaks for IL-6 were observed at days 13, 17 and around birth. Finally, only one
      peak of cells positive for IFN-gamma was detected. Whereas cells positive for IL
      1 were generally grouped and more often localized in the external area of the
      thymus, the other positive cells were isolated and evenly distributed in the
      thymus. Our results illustrated the presence of cytokine transcripts in the
      developing thymus following a developmentally controlled sequence and support the
      hypothesis that cytokines could play a role in T cell development.

PMID- 7826952
TI  - p59fyn tyrosine kinase regulates p56lck tyrosine kinase activity and early TCR
      mediated signaling.
AB  - To study the role of p59fyn in T cell activation, we used antisense RNA to
      inhibit p59fyn expression in a T cell clone. Transfectants with reduced levels of
      p59fyn were functionally impaired in their responses to antigen, Con
      A+recombinant IL-1 and cross-linking with anti-TCR mAb. Induction of tyrosine
      phosphorylation on most intracellular substrates was greatly reduced. We also
      noted that the lck kinase activity was greatly reduced even though the amount of
      lck protein was equivalent to that present in parental D10 cells. Our results
      suggest that the protein tyrosine kinase p59fyn is critical in TCR-mediated
      signaling and also suggests that p59fyn may regulate p56lck tyrosine kinase
      activity.

PMID- 7826953
TI  - Fetal tissue banking--the right time is now.

PMID- 7826954
TI  - The proper measure of intrauterine growth retardation is function, not size.

PMID- 7826955
TI  - Low-dose combined oral contraceptives.

PMID- 7826956
TI  - The quality of routinely collected maternity data.
AB  - OBJECTIVE: To assess the validity of clinical information held on a regional
      maternity database, the St Mary's Maternity Information System (SMMIS). DESIGN: A
      retrospective review of 892 maternity case notes and matched SMMIS records, by a
      midwife trained in clinical coding techniques. SETTING: Three maternity units in
      the North West Thames Region. MAIN OUTCOME MEASURES: Percentage agreement for 17
      directly recorded SMMIS data items and equivalent data abstracted from the notes.
      Frequencies of diagnosis codes abstracted from case notes, as compared with those
      generated by SMMIS on the basis of directly recorded data. RESULTS: A generally
      high level of agreement was observed between the abstracts of the notes and the
      SMMIS records. Of the 17 data items examined, 10 showed 95% agreement or better,
      and all but two exceeded 80% agreement. Little difference was found between the
      levels of agreement observed at the three sites. A greater number and range of
      diagnosis codes were abstracted from the notes than were generated by SMMIS.
      CONCLUSIONS: The directly recorded clinical data held on the SMMIS regional
      database is largely accurate and consistently recorded across a variety of units.
      The database can therefore be considered a valuable resource for the comparative
      audit of maternity practice. The SMMIS technique for deriving, on a semi
      automatic basis, diagnosis codes from the directly recorded fields, appears to
      work moderately well. We suggest that the direct method of data collection used
      in SMMIS could provide a model for other specialties in the National Health
      Service.

PMID- 7826957
TI  - A longitudinal study of bacterial vaginosis during pregnancy.
AB  - OBJECTIVE: To determine the longitudinal changes in the incidence of vaginosis in
      pregnancy. DESIGN: A prospective study of women during pregnancy. SETTING: A
      District General Hospital in North-West London. SUBJECTS: Seven hundred and
      eighteen pregnant women attending antenatal clinics. At their first attendance
      and subsequently, Gram-stained vaginal smears were examined and Mycoplasma
      hominis and Gardnerella vaginalis were sought by culture. RESULTS: Initially, 87
      (12%) women had bacterial vaginosis diagnosed on Gram-stained reading of the
      vaginal smears. Examination of further smears, obtained from 176 women at 36
      weeks of gestation, showed that those whose vaginal flora was normal initially,
      and who went to term, rarely developed vaginosis (three of 127, 2.4%). Samples
      were obtained at 36 weeks gestation from 32 women who had bacterial vaginosis
      initially, and went to term. In almost 50% (15 of 32) of these a normal
      lactobacillus-dominated flora had regenerated. Thirty-five women (5%) had initial
      vaginal smears graded as intermediate. From this group, six of the 17 (35%) women
      from whom samples were obtained at 36 weeks gestation still had flora of an
      intermediate pattern; 10(59%) now had normal flora and only one (6%) had
      developed bacterial vaginosis. Women with bacterial vaginosis were more likely to
      be culture-positive for M. hominis than those with normal flora (34/78 versus
      10/563, odds ratio 42.73 (18.9 to 102.3) P < 0.001), or to be culture-positive
      for G. vaginalis than those with normal flora (35/78 versus 21/563, odds ratio
      21.0 (10.75 to 41.2) P < 0.001). CONCLUSION: Pregnant women do not commonly
      develop bacterial vaginosis after 16 weeks gestation, and if present, it remits
      spontaneously in approximately half of those who reach term. As bacterial
      vaginosis is associated with increased rates of second trimester miscarriage and
      preterm delivery, any treatment aimed at its eradication in pregnancy should be
      given no later than the beginning of the second trimester of pregnancy.

PMID- 7826958
TI  - Umbilical cord blood gas analysis at delivery: a time for quality data.
AB  - OBJECTIVES: To address the practical problems of routine umbilical cord blood
      sampling, to determine the ranges for pH, PCO2 and base deficit and to examine
      the relationships of these parameters between cord vessels. DESIGN: An
      observational study of umbilical cord artery and vein blood gas results. SETTING:
      A large district general hospital in the UK. SUBJECTS: One thousand nine hundred
      and forty-two cord results from 2013 consecutive pregnancies of 34 weeks or more
      gestation, monitored by fetal scalp electrode during labour. RESULTS: Only 1448
      (74.6%) of the 1942 supposedly paired samples had validated pH and PCO2 data both
      from an artery and the vein; 54 (2.8%) had only one blood sample available, 90
      (4.6%) had an error in the pH or PCO2 of one vessel and in 350 (18%) pairs the
      differences between vessels indicated that they were not sampled from artery and
      vein as intended. Only 60% of the cases with an arterial pH less than 7.05 had
      evidence of a metabolic acidosis (base deficit in the extracellular fluid 10
      mmol/l or more). Of all the cases, 2.5% had a venous-arterial pH difference
      greater than 0.22 units. CONCLUSIONS: Both artery and vein cord samples must be
      taken and the results screened to ensure separate vessels have been sampled.
      Interpretation of the results requires the examination of PCO2 and base deficit
      of the extracellular fluid from each vessel as well as the pH. Confusion about
      the value of cord gas measurements may be due to the use of erroneous data and
      inadequate definitions of acidosis which do not differentiate between respiratory
      and metabolic components.

PMID- 7826959
TI  - Episiotomies and the occurrence of severe perineal lacerations.
AB  - OBJECTIVE: To investigate the relation between the use of mediolateral episiotomy
      and the occurrence of severe (third degree) perineal tears in hospital deliveries
      in the Netherlands. DESIGN: An observational study. SUBJECTS: Data were derived
      from the Dutch National Obstetric Database (LVR) of 1990, from which 43,309
      spontaneous, occipito-anterior, vaginal deliveries of live, singleton infants
      were investigated. INTERVENTION: Medio-lateral episiotomy. MAIN OUTCOME MEASURE:
      The occurrence of severe perineal tears. RESULTS: The severe tear rate was 1.4%
      in the total study group. Using multiple logistic regression to control for
      possible confounding variables, the use of mediolateral episiotomy was found to
      be associated with a more than fourfold decrease in risk of severe lacerations
      (odds ratio 0.22, 95% CI 0.17 to 0.29). Further, in a logistic model deliveries
      in hospitals with restrictive use of episiotomy (< 11%) were compared with those
      in hospitals with liberal use of episiotomy (> 50%). Liberal use of episiotomy
      was not associated with a lower frequency of severe perineal tears. CONCLUSION:
      Although a protective effect of mediolateral episiotomy on the occurrence of
      severe lacerations was found, liberal use of mediolateral episiotomy should be
      discouraged on the basis of our findings.

PMID- 7826960
TI  - A randomised prospective study of laparoscopic vaginal hysterectomy versus
      abdominal hysterectomy each with bilateral salpingo-oophorectomy.
AB  - OBJECTIVE: To identify differences in the peri-operative outcome of women
      undergoing hysterectomy with bilateral salpingo-oophorectomy performed either by
      abdominal hysterectomy and bilateral salpingo-oophorectomy or by laparoscopic
      assisted salpingo-oophorectomy and vaginal hysterectomy. To identify any
      potential management implications, including financial differences, between these
      two forms of operations. SUBJECTS AND METHODS: Eighty women undergoing
      hysterectomy and bilateral salpingo-oophorectomy for benign gynaecological
      conditions were prospectively randomised to have the procedure by laparoscopic
      assisted bilateral salpingo-oophorectomy and vaginal hysterectomy or total
      abdominal hysterectomy and bilateral salpingo-oophorectomy. The peri-operative
      and post-operative courses of both groups were compared. RESULTS: Although
      laparoscopic-assisted bilateral salpingo-oophorectomy and vaginal hysterectomy
      took longer (100 (SD 5.6) versus 57 (SD 4.7) min, P < 0.0001), the women
      undergoing this procedure had a shorter time in hospital (3.5 versus six days, P
      < 0.0001) quicker recovery (three versus six weeks, P < 0.0001) and returned to
      work earlier. There were minimal complications in both groups and they were not
      significantly different. The cost of the laparoscopic-assisted procedure was
      greater during the operation with longer operating time and cost of disposable
      instruments. However, the total cost of treatment was less in this group because
      of shortened post-operative stay. CONCLUSION: The study shows laparoscopic
      assisted bilateral salpingo-oophorectomy and vaginal hysterectomy is a safe and
      cost-effective procedure for women requiring a hysterectomy and bilateral
      salpingo-oophorectomy.

PMID- 7826961
TI  - Intravenous immunoglobulin in the prevention of recurrent miscarriage. The German
      RSA/IVIG Group.
AB  - OBJECTIVE: This study was undertaken to verify a specific effect of intravenous
      immunoglobulin on the outcome of pregnancy in patients with a history of
      recurrent miscarriage as an alternative to immunotherapy with allogeneic
      leucocytes. STUDY DESIGN: In a randomised double-blind multicentre study 64
      patients with a history of unexplained primary recurrent miscarriage were treated
      with intravenous immunoglobulin (verum) or 5% human albumin (placebo) infusions
      during their following pregnancy. RESULTS: Success rates for both verum and
      placebo, were compared excluding seven patients with explained miscarriage (20/27
      (74%) versus 21/30 (70%)) and without any such exclusion (20/33 (61%) versus
      21/31 (68%)). The difference between the two groups was not statistically
      significant. CONCLUSIONS: A specific effect of intravenous immunoglobulin in
      primary recurrent miscarriage could not be demonstrated. These results imply the
      possibility of psychological influence, i.e. a placebo effect of intravenous
      immunoglobulin, on the outcome of pregnancy. Since success rates for both verum
      and placebo were in the same range as for treatment with allogeneic leucocytes,
      psychological effects might be responsible also for other kinds of immunotherapy
      for prevention of recurrent miscarriage. However, it cannot be excluded that
      success rates only reflect background values as reported for recurrent
      miscarriage patients without any treatment.

PMID- 7826962
TI  - The use of corticosteroids for maturation of fetal lungs in patients with preterm
      prelabour rupture of the membranes.

PMID- 7826963
TI  - Management of fetal hydrops associated with parvovirus B19 infection.

PMID- 7826964
TI  - Bioactive tumour necrosis factor alpha in pre-eclamptic patients with and without
      the HELLP syndrome.

PMID- 7826965
TI  - Meningo-encephalitis due to listeria monocytogenes in pregnancy.

PMID- 7826966
TI  - Aortic dissection in pregnancy: importance of pregnancy-induced changes in the
      vessel wall and bicuspid aortic valve in pathogenesis.

PMID- 7826967
TI  - Repair of a rectovaginal fistula with traction in a HIV positive patient.

PMID- 7826968
TI  - Computerised measurement of fetal heart rate variation in a case of fetomaternal
      haemorrhage.

PMID- 7826969
TI  - Endometriosis and atypical complex hyperplasia associated with unopposed
      oestrogen therapy.

PMID- 7826970
TI  - Vaginal myomectomy.

PMID- 7826971
TI  - Danazol prophylaxis for delivery in hereditary angioneurotic oedema.

PMID- 7826972
TI  - The use of the fetal electrocardiogram in labour.

PMID- 7826973
TI  - The myth of fetal growth retardation at term.

PMID- 7826974
TI  - The predictive value of outpatient hysteroscopy in a menopause clinic.

PMID- 7826975
TI  - Flexibility in training.

PMID- 7826976
TI  - Induction of labour confers benefit in prolonged pregnancy.

PMID- 7826977
TI  - Immunohistochemical study on blood-brain barrier in congenitally hydrocephalic
      HTX rat brain.
AB  - The purpose of the present study is to examine the blood-brain barrier in brain
      of congenital hydrocephalus HTX rats. We investigated the rat brain from
      postnatal day 1 to 44 using light and electron microscopy and immunohistochemical
      methods with monoclonal anti-blood-brain barrier (BBB) antibody. HTX rats
      developed hydrocephalus at 1-2 days after birth. Most rats succumbed to brain
      changes within 4-5 weeks. Among 136 HTX rats examined, 45 rats succumbed within 1
      week after birth, 29 rats between 1-2 weeks, and 4 rats 27-44 days after birth.
      Out of 88 hydrocephalic rats 54 showed a marked ventricular dilatation, and 34
      showed a mild dilatation. Dilatation of lateral ventricles was mild in the rats
      at 1-2 days after birth, but 3-14-day-old rats showed moderate or marked
      dilatation. 15-30 days after birth the rats developed mostly marked dilatation of
      lateral ventricles and third ventricle. Lateral ventricles and third ventricle
      showed a symmetric dilatation, but ependymal cell layers were well preserved.
      Aqueduct exhibited no dilatation in any rat. There were spongy appearances and
      cystic cavities in the white matter around the lateral ventricles. There were
      glial fibers and capillaries across the cystic cavities. Cystic lesions were also
      found in the deep subcortical white matter, consisting of spongy changes with
      extended extracellular spaces and microcysts in the white matter.
      Immunohistochemically, the anti-BBB reactivity in the normal control rats was at
      first weak at 2 weeks after birth and increased with the course of development,
      prominently 4 weeks after birth. Three- and four-week-old HTX rats with
      hydrocephalus showed moderate positive anti-BBB reaction in the cerebral cortex,
      the basal ganglia, and around the aqueduct but only a very weak reaction in the
      deep subcortical white matter and in the subependymal area of lateral ventricles.
      Laminin immunoreactivity was not different in the capillaries of hydrocephalic
      brain as compared with normal brain. Electron microscopically, tight junctions
      were well formed between endothelial cells of capillaries in the subcortical
      white matter. Occasionally capillaries with partial defect of basal membrane
      could be found, where the cytoplasm of endothelial cell was protruding between
      pericytic cytoplasm. Swelling of astrocytic end-feet were found around the
      microvessels. The results suggest that at the site of the lesion there is
      underdevelopment or immaturity of the blood-brain barrier.

PMID- 7826978
TI  - Characterization of bile ducts in primary biliary cirrhosis and other liver
      diseases by immunohistochemical demonstration of Lewis(a) or b antigen.
AB  - We investigated Lewis(a) and Lewis(b) expression of bile ducts in 68 specimens
      from various kinds of liver disease. In addition, the number of IgM and IgG
      synthesizing plasma cells in the hepatic inflammatory reactions were
      immunostained and counted. We found a statistically significant decrease in the
      number of bile ducts in PBC (primary biliary cirrhosis) in comparison with either
      chronic active or persistent hepatitis (CAH/CPH). Bile ducts could be detected
      easily and constantly by their Lewis antigen expression. Isolated bile duct
      epithelial cells not apparent in H&E sections could be identified by Lewis(a) and
      b immunostaining. The number of plasma cells in PBC was significantly different
      than in (CAH/CPH). A large number of IgM plasma cells was a characteristic
      feature of PBC. However, neither counting of Lewis(a) and b positive bile ducts
      nor counting of IgM plasma cells was of definite diagnostic significance in the
      individual clinical case, since no cut-off value could be determined above or
      below which a PBC was ruled out or proven.

PMID- 7826979
TI  - Studies on the presence of magnesium in visceral amyloid.
AB  - The Magneson and Titan yellow tests were used to detect Mg in amyloid deposits in
      primary and secondary amyloidosis, in a pituitary tumour and in a case of equine
      cutaneous amyloidosis. Especially vascular amyloid deposits turned out to contain
      high levels of Mg. The significance of these findings remains unclear at present.
      Competition between Mg and Ca, the relationship between Mg in elastic fibres and
      amyloid P-component, and the high water content of amyloid along with the
      interaction of Mg with water are discussed.

PMID- 7826980
TI  - [Quantitative studies in lamina V-pyramidal neurons of the frontal brain after
      infantile brain damage].
AB  - Cortical pyramidal neurons (lamina V, Area 10) were investigated in brain autopsy
      material obtained from 8 patients with serious bodily and mental retardation,
      aged between 3 and 24 years. Quantitative neuromorphological estimations of the
      ramification degree, length and spine density of apical or basal single dendritic
      fields (SDF) of these neurons were carried out using the impregnation technique
      of GOLGI and a computer-assisted quantification method. The results were compared
      with related data found in the prefrontal cortex (Area 10 according to Brodmann)
      of patients in the same age without neuropathological or psychiatric
      disturbances. During the normal maturation period the development of dendritic
      length and spine density reflects the diminution of the relative excess of growth
      during the early postnatal phase. When comparing the dendritic length or spine
      density of a SDF in children with that of juvenile adolescents or young adults,
      the length is reduced by 40%, the spine density by 15%. In the brains of mentally
      retarded children we found the dendritic length reduced by 30% (apical) or 40%
      (basal), and a further elongation and ramification of the dendritic tree
      (especially nonramified terminal dendrites) in juvenile adolescents. However, the
      spine density showed a significant deficit of about 30% in children as well as in
      juvenile adolescents. This spine loss may be morphologically related to the
      symptoms of mental retardation. In these cases, the genetically controlled spine
      distribution pattern along the dendritic orders was not changed. The results
      obtained are discussed by taking into consideration data from animal experiments
      as well in view of the normal or disturbed neuronal development.

PMID- 7826981
TI  - Coexpression of epidermal growth factor receptor protein and c-erbB-2 oncoprotein
      in human astrocytic tumors. An immunohistochemical study.
AB  - C-erbB-2-oncoprotein and the epidermal growth factor receptor (EGFR) protein are
      transmembrane glycoproteins with an external ligand-binding domain and a nearly
      homologous internal tyrosine kinase domain. In the present study it was
      investigated in 63 astrocytic tumors (9 astrocytomas G1, 18 astrocytomas G2, 17
      anaplastic astrocytomas G3 and 19 glioblastomas G4) whether the structural
      homology of both glycoproteins correlated with the coexpression in astrocytic
      tumor cells. The immunoreactive products were identified by a computerized image
      analysis. There was no expression of the EGFR-protein in low grade astrocytomas
      (G1, G2) measured by density of gray level. The immunoreactivity increased
      remarkably in anaplastic and malignant gliomas. The number of the c-erbB2
      oncoprotein-reactive tumor cells increased with the progression and
      dedifferentiation of tumors. Significant differences could be found between low
      grade anaplastic astrocytoma as well as glioblastoma. The correlative analysis
      resulted in a significant positive homology with increasing grading level between
      the expression of EGFR- and c-erbB-2 protein. The trend goes in the same
      direction. The results emphasize that EGFR- and c-erbB-2 protein were expressed
      in astrocytic tumors with increased malignancy and dedifferentiation.

PMID- 7826982
TI  - Individual differences between nuclear parameters of normal and malignant breast
      epithelium.
AB  - This study attempts to estimate the status of estrogen and progesterone receptors
      (ER and PR) in tissue of invasive breast carcinoma. Identical stereologic
      parameters of nuclear ultrastructure, of normal and malignant epithelium in the
      same breast were compared. Samples of normal and malignant epithelium of 30
      surgically amputated breasts were analysed morphometrically. The concentration of
      ER and PR in the malignant epithelium was estimated by means of the dextran
      coated charcoal (DCC) method. We measured the mean nuclear area (A), nuclear
      specific density (Sv/Vv) and nuclear numerical density (Nv) of epithelium. The
      comparison of such models of normal and malignant epithelium nuclear
      ultrastructure of the same breast demonstrated: a) the difference between Sv/Vv
      of nuclei very sensitively and specifically marks the ER status in malignant
      tissue (overall efficiency = 80%, p < 0.01), and b) the difference between A,
      Sv/Vv and Nv marks the concordant ER and PR status with identical overall
      efficiency. Minimal individual differences in size, surface structure and shape,
      observed between nuclei of malignant epithelium of positive concordant ER and PR
      status and nuclei of normal epithelium demonstrated that the highest
      morphological similarity is associated with biochemical similarity of cells
      exposed to the identical media of steroid hormones.

PMID- 7826983
TI  - Nuclear morphometry of soft tissue tumors of fibrous origin.
AB  - In this study we investigated the diagnostic significance of a set of different
      morphometric nuclear parameters in the differential diagnosis of soft tissue
      tumors. Nuclear area, the standard deviation of the nuclear area, the shape
      factor and other parameters such as Feret's Diameter and Martin's Radii were
      assessed using a computer assisted image analyzer system. A statistically
      significant difference (p < 0.01) between benign and malignant tumors and tumor
      like lesions could be confirmed for the nuclear area and the standard deviation
      of the nuclear area, with the significance level being lower (p = 0.5) for the
      latter parameter. The shape factor also discriminated between the examined
      groups. Reclassification of the assessed histological diagnosis was performed by
      linear discriminant analysis using all possible combinations of the different
      nuclear parameters. This procedure disclosed an increasing rate of correctly
      reclassified cases with rising number of parameters applied. We conclude that the
      assessment of nuclear parameters may be helpful in the correct diagnosis and
      differential diagnosis of soft tissue tumors and tumor-like lesions of fibrous
      origin.

PMID- 7826984
TI  - Immunohistochemical localization of PDGF B, PDGF beta receptors and IGF I
      receptors during atherogenesis.
AB  - Growth factors and their receptors may be involved in initiation and progression
      of atherosclerotic intima changes. In this study, sections of human arteries in
      different stages of atherosclerosis were investigated for cellular expression of
      PDGF B, PDGF beta receptors and IGF I receptors. The applied immunohistochemical
      approach detected IGF I receptor synthesis in endothelial cells of
      atherosclerotic vessels. A possible role in atherogenesis may be seen in the
      control of IGF I transfer into subendothelial tissues. PDGF B chain production
      was observed in endothelial cells and macrophages in all stages of lesion
      development. The corresponding receptor for PDGF B (PDGF beta receptor) was
      expressed by transformed smooth muscle cells within the thickened intima from the
      stage of macrophage infiltration onwards. These results support the thesis that
      locally produced PDGF acts as a mitogen on smooth muscle cells and may promote
      proliferation during atherogenesis.

PMID- 7826985
TI  - Plasminogen activators and their inhibitor in osteosarcomas and other bone
      tumors.
AB  - The concentrations of the plasminogen activators u-PA and t-PA as well as the
      inhibitor PAI-1 were studied immunohistochemically in 35 osteosarcoma specimens
      compared to 15 Ewing's sarcomas and various other bone lesions. The
      immunoreactivities of plasminogen activators in osteosarcoma specimens were
      significantly higher than PAI-1. Biochemically in cell cultures and
      immunohistochemically in the pathological specimens of the osteosarcomas u-PA was
      the dominant antigen, all factors showing a generally strong reactivity. Here a
      relation to the malignancy and invasivity of the tumors could be seen, which was
      comparable to the results in other tumors. This correlation, however, could not
      be detected in Ewing's sarcomas. On the whole low immunoreactivity of all
      enzymes, and of u-PA in particular, could be seen. In comparison in some benign
      lesions (fibrous dysplasias, aneurysmal bone cysts) the immunohistochemical
      reactions were distinctly stronger. Dominant antigens did not exist in Ewing's
      sarcomas. In all mesenchymal tumors studied the immunohistochemical localisation
      and concentration of the antigens showed a definite correlation with their
      histological differentiation. Chondroblastic differentiations in different tumors
      (chondrosarcomas, enchondromas, chondroblastic osteosarcomas) or chondroid parts
      were always negative for both activators and the inhibitor, especially in their
      central parts. Here, the biological malignancy was not decisive for the result.

PMID- 7826986
TI  - [Generalized septic infections in rheumatoid arthritis. Study of autopsy
      material].
AB  - In the randomized autopsy material of 161 patients with rheumatoid arthritis
      (RA), a letal, generalized septic infection (GSI) was observed in 22 cases
      (13.66%). The GSI was accompanied by a pyarthros in 12 (7.45%) and no pyarthros
      in 10 (6.21%) cases. The clinical parameters of 22 septic RA patients were
      compared with 139 age and sex matched RA patients without GSI. The average age of
      septic patients decreased (p < 0.02), with low serum electrophoretic b-globulin
      level (p < 0.04), and high Waaler-Rose (p < 0.02) and Latex level (p < 0.004).
      The clinical parameters of 22 septic patients were compared with 76 age and sex
      matched RA patients without sepsis, vasculitis, or generalized secondary
      amyloidosis (GSA), and/or miliary epitheloid granulomas of tuberculous type (mT).
      The differences between the two groups of patients were the same, with a
      statistically more pronounced age difference (p < 0.005). 29 out of 161 patients
      (18.01 %) suffered from a clinically manifest diabetes mellitus (in 6 patients
      accompanied by sepsis), and 11 (6.83 %) from a clinically latent diabetes
      mellitus (in 2 patients accompanied by sepsis). There was no significant
      relationship between sepsis and manifest diabetes mellitus. The controlled and
      treated diabetes mellitus does not influence the frequency of lethal sepsis.
      Significant correlations were found between sepsis and latent diabetes mellitus
      (based on the histological detection of amyloid deposition localized to the
      islets of Langerhans (p < 0.02). 34 out of 161 patients (21.12%) suffered from a
      generalized secondary amyloidosis (in 3 patients accompanied by sepsis). There
      was no significant relationship between sepsis and generalized secondary
      amyloidosis. The thickness of adrenal cortex represents the effect of steroid
      therapy. Critical random check, using the Mann-Whitney tests, supports
      significance relationship between the adrenal cortex atrophy and fatal sepsis (p
      < 0.010). The follicular lymphoid depletion in the spleen represents the effect
      of immunosuppressive therapy. The size of lympho-follicles decreased
      significantly in sepsis (p < 0.004). The long term corticosteroid therapy and
      immunosuppressive represent a potential danger for sepsis.

PMID- 7826987
TI  - [Menkes' kinky hair disease: a clinical and pathological case report with special
      reference to glial changes in the brain damage].
AB  - Menkes' kinky hair disease (Kinky hair disease, trichopoliodystrophy) is a rare
      hereditary disease of copper metabolism. In this study we report about the case
      of a boy with a long course of disease who died at the age of 6. The last phase
      of the disease was characterized by an almost uncontrollable excitation stage and
      later by an apallic syndrome. Clinical course and autopsy result are presented
      here. The protracted course obviously led to unusual neuropathological changes.
      In addition to the known neuronal damages an excessive reactive gliosis could be
      found. The unusual neuropathological course of this gliosis perhaps allows the
      conclusion that apart from neuronal damages disturbances of copper metabolism
      have an influence on the glia.

PMID- 7826988
TI  - Solitary eosinophilic granuloma of cerebral lobes. Value of immunohistochemistry
      for a diagnostic interpretation.
AB  - Primary cerebral eosinophilic granuloma is a very rare lesion. In this study we
      report a further observation of solitary fronto-parietal eosinophilic granuloma
      in a child of three years. The immunohistochemical pattern, with the strong
      positivity of the histiocytic cells for PG-M1, an antibody which does not stain
      the Langerhans cells, suggests the reactive nature of the granulomatous lesion.

PMID- 7826989
TI  - [A new method for simultaneous demonstration of senile plaques and Alzheimer's
      neurofibrillary tangles].
AB  - The author completed the method according to Yamaguchi with a sodium hydroxide
      pretreatment, and he also modified the composition of the methenamine-silver
      nitrate solution. The Alzheimer cells as well as the classic (combined, neuritic)
      senile plaques and the diffuse plaques can be impregnated simultaneously with the
      new procedure.

PMID- 7826990
TI  - Food photography. I: The perception of food portion size from photographs.
AB  - Fifty-one male and female volunteers aged 18-90 years from a wide variety of
      social and occupational backgrounds completed 7284 assessments of portion size in
      relation to food photographs. Subjects were shown six portion sizes (two small,
      two medium and two large) for each of six foods, and asked to compare the amount
      on the plate in front of them to (a) a series of eight photographs showing
      weights of portions from the 5th to the 95th centile of portion size (British
      Adult Dietary Survey), or (b) a single photograph of the average (median) portion
      size. Photographs were prepared either in colour or in black and white, and in
      two different sizes. The order of presentation of foods; use of black and white
      or colour; the size of photographs; and presentation of eight or average
      photographs were each randomized independently. On average, the mean differences
      between the portion size presented and the estimate of portion size using the
      photographs varied from -8 to +6 g (-4 to +5%) for the series of eight
      photographs, and from -34 to -1 g (-23 to +9%) for the single average photograph.
      Large portion sizes tended to be underestimated more than medium or small portion
      sizes, especially when using the average photograph (from -79 to -14 g, -37 to 
      13%). Being female, 65 years and over, or retired, or seeing photographs in
      colour, were all associated with small but statistically significant
      overestimations of portion size. Having a body mass index > or = 30 kg/m2 was
      associated with an 8% underestimate of portion size. We conclude that use of a
      series of eight photographs is associated with relatively small errors in portion
      size perception, whereas use of an average photograph is consistently associated
      with substantial underestimation across a variety of foods.

PMID- 7826991
TI  - The effect of subclinical intestinal nematode infection on the diet selection of
      growing sheep.
AB  - To test the hypothesis that subclinical gastrointestinal parasitism, associated
      with an impairment in N digestion and metabolism and a reduction in the voluntary
      feed intake (VFI), could affect the diet selection of sheep given a choice
      between two feeds that differed in their crude protein (CP) content, twenty-four
      Texel x Scottish Blackface ewe lambs growing from 28 to 48 kg live weight (LWT)
      were given a daily dose of 2500 larvae of the intestinal nematode
      Trichostrongylus colubriformis; twenty-four similar lambs were used as uninfected
      controls. Six infected and six control lambs were given a free choice between two
      pelleted feeds (10.4 MJ metabolizable energy/kg), with different CP contents (90
      (L) and 214 (H) g CP/kg fresh feed respectively). In addition, eighteen
      parasitized and eighteen control sheep were given access ad lib. to either feed
      L, or feed H, or their mixture M (164 g CP/kg; twelve per feed), in order to
      quantify the effects of the feeds when offered alone, and to test for any
      interactions between feed CP content and parasitism on the performance of the
      lambs. Intestinal parasitism reduced significantly (P < 0.001) both the rates of
      LWT gain (by 30%) and VFI (by 10%). The adult and developing parasitic forms took
      4 weeks to establish and develop to a significant adult worm population (as
      judged by the faecal egg counts and blood variables) and until then there was no
      effect of parasitism on the performance of the lambs. The diet selection of the
      lambs given a choice between two feeds was similar between the two groups in the
      first 4 weeks of the experiment, but differed significantly (P < 0.05) in the
      second part of the experiment (4th week to the end). Thus, while parasitized
      lambs had a reduced rate of feed intake, by changing their diet selection they
      achieved a daily rate of CP intake similar to the control ones. However, since
      the parasitized lambs had a reduced rate of LWT gain, they also consumed a higher
      total amount of CP to reach the same LWT. It is concluded that sheep infected
      daily with a small number of larvae of T. colubriformis and given a choice
      between two feeds that differ in their protein contents are able to modify their
      diet selection in order to meet the increased protein requirements resulting from
      such an infection.

PMID- 7826992
TI  - Simulation of the dynamics of protozoa in the rumen.
AB  - A modified mathematical model is described that simulates the dynamics of rumen
      micro-organisms, with specific emphasis on the rumen protozoa. The model is
      driven by continuous inputs of nutrients and consists of nineteen state
      variables, which represent the N, carbohydrate, fatty acid and microbial pools in
      the rumen. Several protozoal characteristics were represented in the model,
      including preference for utilization of starch and sugars compared with fibre,
      and of insoluble compared with soluble protein; engulfment and storage of starch;
      no utilization of NH3 to synthesize amino acids; engulfment and digestion of
      bacteria and protozoa; selective retention within the rumen; death and lysis
      related to nutrient availability. Comparisons between model predictions and
      experimental observations showed reasonable agreement for protozoal biomass in
      the rumen, but protozoal turnover time was not predicted well. Sensitivity
      analyses highlighted the need for more reliable estimates of bacterial engulfment
      rate, protozoal maintenance requirement, and death rate. Simulated protozoal
      biomass was increased rapidly in response to increases in dietary starch content,
      but further increases in starch content of a high-concentrate diet caused
      protozoal mass to decline. Increasing the sugar content of a concentrate diet,
      decreased protozoa, while moderate elevations of the sugar content on a roughage
      diet increased protozoal biomass. Simulated protozoal biomass did not change in
      response to variations in dietary neutral-detergent fibre (NDF) content.
      Reductions in dietary N resulted in an increased protozoal biomass. Depending on
      the basal intake level and dietary composition, protozoal concentration in the
      rumen was either increased or decreased by changes in feed intake level. Such
      changes in relative amounts of protozoal and bacterial biomass markedly affected
      the supply of nutrients available for absorption. The integration of protozoal,
      bacterial and dietary characteristics through mathematical representation
      provided an improved understanding of mechanisms of protozoal responses to
      changes in dietary inputs.

PMID- 7826993
TI  - Effects of different supplements on splanchnic oxygen consumption and net fluxes
      of nutrients in sheep consuming bromegrass (Bromus inermis) hay ad libitum.
AB  - Fifteen sheep (53 kg), with catheters in a hepatic vein, the portal vein and a
      mesenteric vein and artery, were offered a bromegrass (Bromus inermis) hay (104 g
      crude protein (CP), 700 g neutral-detergent fibre and 65 g acid-detergent
      lignin/kg dry matter (DM) ad lib. with different supplements to determine the
      effects on net flux of oxygen and nutrients across the portal-drained viscera
      (PDV) and liver. The sheep were unsupplemented (Control) or received 5 g DM/kg
      body weight (BW) of ground maize (M), 7 g DM/kg BW of soya-bean hulls (H) or 0.73
      g DM/kg BW of a mix of feedstuffs high in rumenundegradable protein (P). Apparent
      digestible energy (DE) intakes were 5.3, 10.4, 10.6 and 6.7 (SE 0.74) MJ/d and
      apparent digestible CP intakes were 37, 50, 79 and 68 (SE 4.3) g/d for Control,
      M, H and P treatments respectively. Splanchnic tissue oxygen consumption rates
      were 0.23, 0.32, 0.30 and 0.27 (SE 0.054) mol/h, and oxidative metabolism
      accounted for 0.46, 0.31, 0.33 and 0.47 (SE 0.051) of DE intakes for Control, M,
      H and P treatments respectively. Supplements increased (P < 0.05) release of
      alpha-amino nitrogen (AAN) by the PDV (4.2, 17.5, 19.6 and 18.1 mmol/h for
      Control, M, H and P treatments respectively). Splanchnic net flux of AAN was not
      affected by supplement treatments. Hepatic release of urea-N was increased (P <
      0.05) by supplement treatments (27, 40, 46 and 44 mmol/h for Control, M, H and P
      respectively); the P treatment increased (P < 0.05) and the H treatment tended (P
      = 0.10) to increase splanchnic release of urea-N (7, 10, 20 and 27 mmol/h for
      Control, M, H and P treatments respectively). Net flux of glucose across the PDV
      was -4.6, 1.4, -5.6 and -7.2 (SE 1.65) mmol/h for Control, M, H and P treatments
      respectively. Hepatic glucose released averaged 23 (SE 2.0) mmol/h and was not
      affected by treatment. Treatments M and H increased (P < 0.05) PDV release of
      propionate compared with the Control treatment (4.5, 15.5, 16.8 and 7.7 mmol/h
      for Control, M, H and P treatments respectively). Release of acetate by the PDV
      was 43, 97, 118 and 67 (SE 23.9) mmol/h for Control, M, H and P treatments
      respectively. In summary, different supplements of low-quality grass did not
      increase the efficiency of N metabolism by splanchnic tissues. Treatment P had
      little effect on net flux across splanchnic tissues of glucose, L-lactate, beta
      hydroxybutyrate and volatile fatty acids (VFA).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7826994
TI  - Digestibility of krill (Euphausia superba and Thysanoessa sp.) in minke whales
      (Balaenoptera acutorostrata) and crabeater seals (Lobodon carcinophagus).
AB  - Apparent digestible efficiency (% DE) was studied by use of dietary Mn as an
      inert marker, in minke whales (Balaenoptera acutorostrata) and crabeater seals
      (Lobodon carcinophagus) which had been eating krill. Median % DE in minke whales
      (n5) eating krill of the genus Thysanoessa sp. (energy density (ED) 23.8 kJ/g)
      was 93 (range 87-93). Median % DE in crabeater seals (n6) eating krill of the
      species Euphausia superba (ED 20.8 kJ/g) was 84 (range 79-85), which is
      significantly lower than the % DE of krill in minke whales (P = 0.008). Since the
      chemical composition in E. superba and in Thysanoessa sp. is similar, it is
      suggested that the complex multi-stomached system of minke whales, which contains
      both chitinase (EC 3.2.1.14)-producing as well as several other types of
      bacteria, is superior to the single-stomached system of crabeater seals with
      regard to krill digestion. It is worth noting, however, that the % DE of krill in
      the crabeater seal is still very high.

PMID- 7826995
TI  - Effects of reducing the starch content in oat-based diets with cellulose on
      jejunal flow and absorption of glucose over an isolated loop of jejunum in pigs.
AB  - Four pigs fitted with two sets of re-entrant cannulas in the upper jejunum were
      used to study the effect of two oat-flour (F)- and oat-bran (B)-based diets
      without or with (FC and BC respectively) addition of 148 g wood cellulose/kg on
      jejunal flow and absorption of glucose over an isolated loop of jejunum. Mean
      transit time (MTT) of flow from the proximal re-entrant cannula increased from
      approximately 1.5 h with diet F to 2 h when feeding diet BC. Both the replacement
      of oat flour by oat bran and the supplementation of the diets with cellulose led
      to a significantly longer MTT for dry matter and the carbohydrates, except that
      cellulose did not have a significant effect on the mTT for the total non-starch
      polysaccharides. Only the addition of cellulose significantly delayed gastric
      emptying of the added liquid-phase (Polyethylene glycol 4000) and solid-phase
      (Cr2O3) markers, whereas no effect of the oat source used was seen. Feeding diets
      with a higher level of dietary fibre (DF) and lower content of starch, obtained
      by substitution with cellulose or by feeding oat bran instead of oat flour,
      reduced the recovery of starch from an isolated loop of jejunum. Consequently,
      the quantitative absorption of starch was not significantly different between
      diets when starch was related to the recovery of external markers. However, when
      related to the recovery of arabinoxylan (AX) there was a significantly lower
      absorption of starch from the bran-based diets in comparison with the flour-based
      diets. The capacity to digest and absorb the large quantities of starch entering
      the duodenum after a carbohydrate-rich meal appears to be the limiting factor for
      absorption in the upper jejunum. Therefore, any effect of DF on the rate of
      absorption of glucose is presumably an effect on gastric emptying rather than
      displacement of the site of starch absorption in the small intestine.

PMID- 7826996
TI  - Effect of dose and modification of viscous properties of oat gum on plasma
      glucose and insulin following an oral glucose load.
AB  - An extract from oats known as oat gum (OG) is composed mainly of the
      polysaccharide (1-->3) (1-->4)-beta-D-glucan, which is highly viscous in aqueous
      solution. Viscous polysaccharides are known to attenuate postprandial plasma
      glucose and insulin responses. The purposes of this study were to determine the
      dose-response to OG and establish quantitatively the effect of viscosity on
      plasma glucose and insulin levels of healthy humans consuming 50 g glucose.
      Increasing the dose of OG successively reduced the plasma glucose and insulin
      responses relative to a control without gum. Reduction of the viscosity of OG by
      acid hydrolysis reduced or eliminated the capacity to decrease postprandial
      glucose and insulin levels. The ability of OG to modify glycaemic response was
      unchanged following agglomeration in the presence of maltodextrin. Agglomerated
      gum dispersed smoothly in a drink without formation of lumps, and development of
      maximum viscosity was delayed. These properties improve palatability. There was a
      highly significant linear relationship between log[viscosity] of the mixtures
      consumed and the glucose and insulin responses. The relationship shows that 79
      96% of the changes in plasma glucose and insulin are attributable to viscosity,
      and that changes occur at relatively low doses and viscosities.

PMID- 7826997
TI  - Ascorbic acid deficiency in guinea pigs: contrasting effects of tissue ascorbic
      acid depletion and of associated inanition on status indices related to collagen
      and vitamin D.
AB  - To investigate the sensitivity of guinea pig tissues to ascorbic acid depletion,
      as distinct from inanition, young male guinea pigs were maintained with either
      ascorbic acid restriction or total diet restriction for 8 weeks. One group (A)
      received no ascorbic acid for 3 weeks, then 0.5 mg/d for 5 weeks; one group (B)
      was weight-matched by restricted food intake to the first group; a third
      (marginally deficient) group (C) received 1 mg ascorbic acid/d throughout; a
      fourth was weight-matched to this group (D); and a fifth group received the
      control diet ad lib. (E). Both of the groups with restricted ascorbic acid
      intakes (A and C) developed very low tissue ascorbic acid contents, but only the
      first group (severely deficient group A) also exhibited a severely reduced growth
      rate. This group also exhibited reduced femur calcium and hydroxyproline contents
      and reduced skin hydroxyproline content. These changes were not seen in the
      corresponding weight-matched group (B). Neither plasma alkaline phosphatase (EC
      3.1.3.1) activity, nor a variety of indices of vitamin D status exhibited changes
      which could be attributed specifically to reduced ascorbic acid intake and hence
      to lowered tissue ascorbic acid content. It is concluded that low tissue ascorbic
      acid levels in guinea pigs clearly alter the connective tissue composition of
      growing femur and skin, but do not necessarily produce a major, specific effect
      on vitamin D status. Moreover, the control of inanition is crucial to permit
      interpretation of the changes in metabolism that are caused by ascorbic acid
      deficiency.

PMID- 7826998
TI  - Zinc changes in blood and urine during cyclic parenteral nutrition: relationships
      with amino acid metabolism.
AB  - Serum Zn, ultrafiltrable Zn and amino acids in serum and urine samples of twenty
      seven patients receiving cyclic (12 h/24 h) parenteral nutrition were measured.
      These samples were collected in patients after a 12 h period of parenteral
      nutrition, and in the evening after 12 h without parenteral nutrition. The same
      determinations were performed in ten control subjects who followed the same
      sampling scheme. Total serum ultrafiltrable Zn showed no significant variations
      in the patients during parenteral nutrition, and was not significantly different
      in the two groups although the proportion of the Zn present in the ultrafiltrable
      fraction was elevated. Serum cystine levels were significantly higher (P = 0.05)
      in the patients than the control subjects, and cystine excretion was also higher
      in patients (P < 0.05) and increased after parenteral nutrition (56.0 (SE 6.5) v.
      147.1 (SE 20.6) mumol/12 h; P < 0.001). Histidine levels did not vary
      significantly in serum after parenteral nutrition and were not different in the
      patients in comparison with the control subjects. Histidine excretion was not
      different in the two groups but increased significantly during parenteral
      nutrition (P < 0.05). Serum albumin was significantly depressed in the patients
      compared with the control subjects (45.3 (SE 1.5) v. 33.9 (SE 1.5) g/l; P <
      0.001). These results suggest that cystine infusion and excretion relate to the
      changes occurring in serum Zn and in urinary Zn excretion.

PMID- 7826999
TI  - Influence of Korean pine (Pinus koraiensis)-seed oil containing cis-5,cis-9,cis
      12-octadecatrienoic acid on polyunsaturated fatty acid metabolism, eicosanoid
      production and blood pressure of rats.
AB  - The effects of dietary Korean pine (Pinus koraiensis)-seed oil containing a
      peculiar trienoic acid (cis-5,cis-9,cis-12-18:3, pinolenic acid, approximately
      18%) on various lipid variables were compared in rats with those of flaxseed
      (Linum usitatissimum L.) oil, safflower (Carthamus tinctorius L.) oil and evening
      primrose (Oenothera biennis L.) oil under experimental conditions where the
      effects of different polyunsaturated fatty acids could be estimated. In Sprague
      Dawley rats fed on diets containing 100 g fat and 5 g cholesterol/kg, the
      hypocholesterolaemic activity of pinolenic acid was intermediate between alpha
      linolenic and linoleic acids. Analysis of the fatty acid composition of liver
      phosphatidylcholine indicated that, in contrast to alpha-linolenic acid,
      pinolenic acid does not interfere with the desaturation of linoleic acid to
      arachidonic acid. However, the effects on ADP-induced platelet aggregation and
      aortic prostacyclin production were comparable. When spontaneously hypertensive
      rats were fed on diets containing 100 g fat/kg but free of cholesterol, gamma
      linolenic and pinolenic acids, as compared with linoleic acid, increased
      prostacyclin production and tended to reduce platelet aggregation. In addition,
      pinolenic acid attenuated the elevation of blood pressure after 5 weeks of
      feeding. Thus, the results of the present studies indicate the beneficial effects
      of pinolenic acid on various lipid variables.

PMID- 7827001
TI  - The needs of readers.

PMID- 7827000
TI  - Effects of short- and long-term feeding of L-carnitine and congeners on the
      production of eicosanoids from rat peritoneal leucocytes.
AB  - The effect of short- and long-term feeding with L-carnitine, L-acetyl carnitine
      and L-propionyl carnitine on the production of eicosanoids from in vitro
      stimulated carrageenan-induced rat peritoneal macrophages was investigated. Both
      young (4 weeks) and old (18 months) rats were used. A lower number of cells was
      isolated from the peritonea of treated than control young rats after 4 d feeding,
      but after 60 d no differences were observed. A similar reduction in cell number
      was found when old animals were given L-acetyl carnitine or L-propionyl carnitine
      (acutely) or L-acetyl carnitine or L-carnitine (chronically). Plasma carnitine
      levels were higher in young rats given carnitine both chronically and acutely.
      Carnitine derivatives were without effect. In contrast, levels of total carnitine
      in the plasma of old rats given L-carnitine and L-acetyl carnitine for 4 d and 60
      d were higher than in controls. There was no correlation between total plasma
      carnitine level and effects on prostaglandin, thromboxane and leukotriene B4
      (LTB4) production. In young rats the most important changes were observed in
      relation to the production of prostacyclin (PGI2), measured as 6 keto
      prostaglandin F1 alpha. Prostacyclin production was higher in the groups given
      carnitine or its derivatives. The net result of the changes in PGI2 was that the
      6 keto-prostaglandin F1 alpha: thromboxane B2 and the 6-keto-prostaglandin F1
      alpha: LTB4 ratios tended to be higher in cells from young animals following
      short-term feeding with L-carnitine.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7827002
TI  - The influence of exercise on the energy requirements of adult males in the UK.
AB  - Energy expenditure was measured over 10 d using the doubly-labelled water (DLW)
      and activity diary methods in summer and winter in subjects with 'light'
      occupations but leisure activities which ranged from 'non-active' to 'very
      active'. The basal metabolic rate (BMR) and the energy cost of activities were
      determined by indirect calorimetry. The Department of Health (1991) predicted BMR
      for the group (6.89 (SD 0.30) MJ/d; n 18) was not significantly different from
      the measured value (7.17 (SD 0.70) MJ/d; n 18). The range of DLW-derived
      expenditure values within the group was BMR x 1.41 to 2.41. The largest seasonal
      change within individuals was BMR x 0.5. The energy expenditure of the group as a
      whole was lower in winter (BMR x 1.88; SD 0.33; n 9) than summer (BMR x 2.01; SD
      0.30; n 9) though the difference was not statistically significant. The average
      summer and winter DLW-derived expenditure was BMR x 1.96 (SD 0.31; n 17). The
      activity diary estimate of expenditure was BMR x 1.79 (SD 0.32; n 17). In a
      subset of the group who were representative of the most active 26% of all adult
      males in the UK, the DLW-derived expenditure was BMR x 2.08 (SD 0.24; n 11). This
      is higher than the highest Department of Health (1991) estimate of BMR x 1.6 for
      individuals in light occupations. The measured energy costs of low-intensity
      activities were similar to those presented in the Department of Health (1991)
      report but the value determined for running (BMR x 13.08; SD 2.4; n 6) was higher
      than the highest value in the report (BMR x 6 to 8). The results indicate that
      the recent Department of Health (1991) reference values for energy may
      underestimate the expenditure of a significant proportion of the UK population
      largely because the energy costs of activity used in the report to calculate
      expenditure do not accurately reflect those achieved during active leisure in
      individuals who take regular exercise.

PMID- 7827003
TI  - Maternal protein reserves and their influence on lactational performance in rats.
      3. The effects of dietary protein restriction and stage of lactation on milk
      composition.
AB  - The effects of severe protein restriction following parturition on the changes in
      rat milk composition during lactation were investigated using multiparous female
      Sprague-Dawley rats caged individually following mating and offered a high
      protein diet (H; 215 g crude protein (N x 6.25; CP)/kg dry matter (DM)) ad lib.
      until parturition. Following parturition, half the females continued to receive
      diet H, whilst the remainder were offered a diet low in protein (L; 90 g CP/kg
      DM) ad lib. On days 2, 4, 8 and 12 of lactation groups of females from both
      dietary treatments were used to provide a milk sample. Milk samples were analysed
      for their lactose (enzymically), protein (binding to Coomassie blue), lipid
      (gravimetrically) and mineral (spectrophotometrically) contents. The milk lactose
      concentration of group H increased with stage of lactation (r2 0.85, P < 0.001).
      Such an increase was prevented by diet L, and from day 8 of lactation the milk
      lactose of group L was lower (P < 0.05) than in group H. Group H milk protein
      concentration did not change during lactation and averaged 90.7 mg/g. Dietary
      protein restriction reduced the milk protein concentration of group L so that on
      days 2, 4 and 12 of lactation it was lower (P < 0.05) than that of group H. On
      day 8 of lactation the milk protein concentration of group L had increased (P <
      0.05) and was comparable with that of group H. For group H, milk lipid averaged
      166.8 mg/g and was generally unchanged during lactation. Diet L increased (P <
      0.01) the milk lipid concentration (205.5 mg/g) compared with diet H and this was
      also significant on days 4 and 8 of lactation (P < 0.05). Group L milk lipid
      concentration also increased between days 4 and 8 of lactation (P < 0.05). Milk
      Na concentration declined during lactation in both dietary groups (P < 0.01) but
      was unaffected by dietary treatment. Both milk Ca and P concentrations increased
      (P < 0.01) during lactation in both dietary groups, whilst protein restriction
      also increased the Ca and P concentrations (P < 0.05). Milk K and Mg
      concentrations were unaffected by dietary treatment or stage of lactation. This
      significant alteration in the milk composition of severely protein-restricted
      dams, while possibly favouring the disposal of greater quantities of energy
      yielding nutrients, suggests that equations developed for the estimation of milk
      production in rats cannot be used under such conditions.

PMID- 7827004
TI  - Maternal protein reserves and their influence on lactational performance in rats.
      4. Tissue protein synthesis and turnover associated with mobilization of maternal
      protein.
AB  - The present study was undertaken to investigate the changes in muscle protein
      turnover involved in the rapid mobilization of protein in rats subjected to
      severe protein restriction during lactation. Estimates of mammary gland and liver
      protein synthesis were also made during lactation. Multiparous female Sprague
      Dawley rats, caged individually following mating, were offered a high-protein
      diet (H; 215 g crude protein (N x 6.25; CP)/kg dry matter (DM)) ad lib. until
      parturition. Following parturition, half the females continued to receive diet H,
      whilst the remainder were offered a diet low in protein (L; 90 g CP/kg DM) ad
      lib. On days 2, 4, 8 and 12 of lactation, groups of females were used in the
      estimation of tissue protein synthesis (flooding dose of [3H]phenylalanine)
      immediately after a milk sample had been obtained. Rates of muscle protein
      synthesis were unchanged during lactation in group H. The feeding of diet L
      during lactation reduced the muscle protein synthesis on day 12 to rates that
      were lower than group H and also the rate on diet L on day 2 (P < 0.01). However,
      this fall in muscle protein synthesis was not rapid and muscle fractional
      synthesis rate (FSR) was different from group H only from day 8 (P < 0.05).
      Estimated rates of mammary protein synthesis appeared to be generally unchanged
      by dietary treatment or stage of lactation. Liver FSR was also unchanged by
      dietary protein supply or stage of lactation. The effect of dietary protein
      restriction on liver size and protein content during lactation influenced liver
      absolute synthesis rate (ASR), and on days 8 and 12 of lactation liver ASR was
      lower in group L than in group H (P < 0.001). The loss of muscle protein in rats
      fed on diet L during lactation (133 mg) occurred mainly between days 2 and 8 of
      lactation and was primarily associated with a dramatic increase in degradation
      (13.0% per d), with the decline in synthesis having a much smaller role. A
      decline in muscle protein degradation during the latter half of lactation was
      part of the mechanism that prevented excessive muscle protein catabolism. It is
      thought that the estimation of mammary protein synthesis in the present study was
      impaired by the milk sampling procedure previously used.

PMID- 7827005
TI  - Amino acid composition of the milk of some mammalian species changes with stage
      of lactation.
AB  - To determine whether the amino acid composition of milk changes during lactation,
      we compared the amino acid pattern (concentration of each individual amino acid
      relative to the total amino acid concentration) of colostrum with that of mature
      milk in six mammalian species. In the human, horse, pig and cow, the pattern of
      amino acids changed between colostrum and mature milk: glutamate, proline,
      methionine, isoleucine and lysine increased; cystine, glycine, serine, threonine
      and alanine decreased. In these four species, the total amino acid concentration
      also decreased 75% between colostrum and mature milk. In the baboon (Papio
      cynocephalus anubis and Papio cynocephalus anubis/Papio cynocephalus
      cynocephalus) and rhesus monkey (Macaca mulatta), however, there was little
      change in the pattern of amino acids between colostrum and mature milk, and total
      amino acid concentration decreased only about 25% between colostrum and mature
      milk. Mature milk rather than colostrum was the most similar among the three
      primates in both amino acid pattern and total amino acid concentration. We
      conclude, in those species in which total amino acid concentrations decline
      substantially between colostrum and mature milk, amino acid patterns also change.
      The presence of a change in amino acid pattern and total amino acid concentration
      during lactation appears to be unrelated to phylogenetic order.

PMID- 7827006
TI  - Identification of sulphur-rich proteins which resist rumen degradation and are
      hydrolysed rapidly by intestinal proteases.
AB  - Several proteins with high proportions of S-containing essential amino acids were
      incubated in sheep rumen fluid in vitro and their rate of digestion was examined
      by sodium dodecyl sulphate-polyacrylamide-gel electrophoresis. The S-rich
      proteins rice prolamin (10 kDa), maize zein (10 kDa) and the 3.2 kDa pumpkin
      (Cucurbita maxima L.) trypsin inhibitor-1 (CMTI-1) were highly resistant to rumen
      fluid degradation, relative to control proteins of known degradation rate
      (casein, bovine serum albumin (BSA) and pea (Pisum sativum) albumin-1 (PA1)).
      Comparison of PA1 and a recombinant N-terminal epitope-tagged PA1 indicated that
      addition of the epitope caused a slight increase in resistance to rumen
      degradation. The proteins were also incubated with a mixture of trypsin (EC
      3.4.21.4) and chymotrypsin (EC 3.4.21.1). PA1, BSA and casein were hydrolysed
      less rapidly than rice prolamin, maize zein and CMTI-1. Digestion by these
      intestinal proteases appeared to be complete. Thus, the prolamin, zein and CMTI-1
      proteins are suitable candidates for expression as foreign proteins in pasture
      plants to increase throughput and uptake of essential amino acids in sheep.

PMID- 7827007
TI  - Absorption of zinc from lupin (Lupinus angustifolius)-based foods.
AB  - The absorption of Zn from a lupin (Lupinus angustifolius) milk fortified with Ca,
      a bread containing lupin flour (230 g/kg), a sauce containing lupin flour and a
      sauce containing a lupin-protein isolate was determined in humans by measuring
      the whole-body retention of radioisotope from meals labelled with 0.02 MBq 65Zn,
      allowing for endogenous excretion of Zn, after 14 d. The absorption of Zn from
      the Ca-enriched milk (16.2%) and the bread made with lupin flour (27.0%) was
      similar to literature figures for comparable soya-bean products. The absorption
      from composite meals made with lupin flour (28.2%) and protein isolate (32.7%)
      was significantly higher than that reported for comparable soya-bean products. In
      a second experiment the absorption of Zn from a lupin-milk base and a soya-bean
      milk base was compared with that from Ca-supplemented bases. The absorption of Zn
      from the lupin-milk base (26.3%) was significantly higher than from the soya-bean
      milk base (17.6%), and neither was significantly altered by the addition of Ca.
      Overall the absorption of Zn from lupin-protein foods was found to be higher than
      from comparable soya-bean products. Lupin milk could be an attractive alternative
      to soya-bean milk for infant formulas.

PMID- 7827008
TI  - Selenium from beef is highly bioavailable as assessed by liver glutathione
      peroxidase (EC 1.11.1.9) activity and tissue selenium.
AB  - The bioavailability of Se from ground beef has been previously found in this
      laboratory to be greater than that of selenite or selenate when fed to female
      Fischer 344 rats. In the present study we examined the bioavailability of Se from
      various commercial portions of beef, the liver, striploin, round, shoulder and
      brisket. All beef was cooked, freeze-dried, finely powdered and mixed with the
      other dietary ingredients. The experimental diets were fed to the weanling
      Fischer 344 rats which had been subjected to dietary depletion of Se for 6 weeks.
      The bioavailability of Se from the beef diets was compared with that of Se as
      selenite or L-selenomethionine (SeMet) added to torula-yeast diets. Each
      experimental diet contained 0.10 mg Se/kg. After 8 weeks of dietary Se repletion,
      relative activity of liver glutathione peroxidase (EC 1.11.1.9; GSHPx) from the
      different dietary groups compared with that of control animals (100%) was (%):
      selenite 91, SeMet 122 (P < 0.05), liver 108, striploin 105, round 106, shoulder
      106, brisket 103. Se recovery for liver GSHPx was generally highest from SeMet >
      beef muscle = beef liver > selenite. Muscle tissue deposition of Se was highest
      from SeMet > beef muscle > selenite = beef liver. In addition, the faecal
      excretion of Se was lowest from the SeMet dietary group and highest from the
      selenite dietary group. The experimental results suggest that all cuts of beef
      appear to be highly bioavailable sources of dietary Se when compared with
      selenite or L-SeMet.

PMID- 7827009
TI  - True fractional calcium absorption in Chinese children measured with stable
      isotopes (42Ca and 44Ca).
AB  - True fractional Ca absorption (TFCA) was compared in children with different
      habitual Ca intakes using a double-label stable-isotope technique. Chinese
      children aged 7 years from Hongkong (n22) and Jiangmen (n12) participated in the
      study. An oral administration of 8 mg 44Ca in 100 g chocolate milk was given
      shortly after an intravenous injection of 0.75 mg 42Ca. Ca isotopic ratios were
      determined in urine samples collected 24 h later using thermal-ionization mass
      spectrometry. There was no significant difference in TFCA between Jiangmen and
      Hongkong children (P = 0.16). TFCA of a lower-Ca-intake group (Ca < or = 500
      mg/d, n19) with mean Ca intake 359 mg/d was 63.1 (SD 10.7)% and that of a higher
      Ca-intake group (Ca > 500 mg/d, n15) with mean Ca intake 862 mg/d was 54.8 (SD
      7.3)%; the difference in TFCA was significant (P = 0.016). Serum levels of 25
      hydroxycholecalciferol of the children were adequate (33.7 (SD 7.7) ng/ml). The
      present study indicates that growing children accustomed to a low-Ca diet appear
      to be able to enhance their absorptive capacity. If it is assumed that dietary Ca
      absorption by Chinese children resembles their TFCA from a single meal of
      chocolate milk, then the recommended dietary allowance (RDA) for Ca for Chinese
      children would be lower than the US RDA (800 mg/d), which is based on an
      estimated 40% Ca absorption as reported for Caucasian children. A comparative
      absorption study is necessary to determine whether there is any difference in
      TFCA between Caucasian and Chinese children.

PMID- 7827010
TI  - The effects of iron deficiency and iron overload on cell-mediated immunity in the
      mouse.
AB  - The influence of Fe status on cell-mediated immunity was studied in weanling mice
      fed on Fe-deficient (7 mg Fe/kg), Fe-sufficient (120 mg Fe/kg) and high-Fe (3000
      or 5000 mg Fe/kg) diets for 7 weeks. The contact sensitivity (CS) response to
      dinitrofluorobenzene (DNFB), the in vivo delayed-type hypersensitivity (DTH)
      response to sheep erythrocytes (SRBC) and the ability of primed spleen cells to
      transfer DTH response to naive normal mice were suppressed in mice consuming the
      Fe-deficient diet. High-Fe diets (3000 or 5000 mg Fe/kg) selectively suppressed
      the CS response to DNFB, but the DTH response to SRBC or the transfer of DTH
      response by primed spleen cells to naive normal mice remained normal. Spleen cell
      functions associated with the expression of class II major histocompatibility
      (MHC) surface antigens, concanavalin A-induced interleukin-2 (IL-2) secretion or
      the antigen-presenting cell (APC) ability to stimulate antigen-dependent
      proliferation of an SRBC-specific helper T-lymphocyte clone were not altered by
      Fe status. However, consistent with the suppressed DTH response in the Fe
      deficient mice was the suppressed concanavalin A-induced T-lymphocyte
      blastogenesis and the interferon-gamma (INF-gamma) production by spleen cells
      from mice fed on the Fe-deficient diet. Spleen cells from mice fed on excess
      levels of Fe in the diet secreted less INF-gamma than the control mice, although
      T-lymphocyte proliferation remained unaffected. Suppression of the cellular
      immune response associated with Fe deficiency may be related in part to impaired
      T-lymphocyte proliferation and INF-gamma secretion rather than to deficits in IL
      2 secretion or APC function.

PMID- 7827011
TI  - Pteroylglutamic (folic) acid in different feedstuffs: the pteroylglutamate
      content and an attempt to measure the bioavailability in pigs.
AB  - Sixty piglets selected after weaning at 4 weeks of age were assigned to five
      replicates of twelve animals each. In each of these replicates the postprandial
      variations in serum pteroylglutamate after the ingestion of twelve sources of
      dietary pteroylglutamic acid were recorded twice weekly at 10 and 16 weeks of
      age. In six of these sources of pteroylglutamic acid the chemically pure form of
      the vitamin was incorporated into a semi-purified diet at concentrations varying
      between 0 and 1.0 mg/kg. The six other sources were provided by a soya-bean meal,
      rapeseed meal, maize, barley, wheat, and a commercial vitamin premix. The
      concentrations of pteroylglutamates measured by radioimmunoassay in the different
      feedstuffs were, in most cases, far from the values reported in the literature,
      except for maize. Indeed, while total pteroylglutamates in barley, wheat and
      rapeseed meal were lower by 35-56%, 17-50% and 60% respectively compared with
      references values, the corresponding values for soya-bean meal ranged from one
      third to twice as much. The area under the curve (AUC) of the pre- and
      postprandial (1, 2, 3, 5 and 7 h) serum pteroylglutamate following ingestion of
      increasing levels of chemically pure pteroylmonoglutamic acid was used to derive
      a regression for the 100% bioavailability of dietary pteroylglutamic acid. The
      corresponding AUC for the feedstuff sources of pteroylglutamates were used in the
      regression to determine the proportion of bioavailable pteroylglutamates out of
      total pteroylglutamates measured in these ingredients. No relationship (P > 0.66)
      was found between the level of chemically pure dietary pteroylmonoglutamic acid
      and the postprandial AUC. In fact, there was no significant (P > 0.11) increase
      in the postprandial concentration of serum pteroylglutamate for any of the
      pteroylglutamate sources used except for wheat. Moreover, values tended (P <
      0.08) to be lower at 5 and 7 h postfeeding except for wheat and barley. It was
      hypothesized that this decrease is probably linked to the postfeeding variation
      in bile secretion which drains considerable amounts of circulatory
      pteroylglutamates. The results of the present experiment indicate that further
      research on analytical procedure is needed in order to provide a reliable method
      for measuring concentrations of pteroylglutamic acid in different sources of a
      given feedstuff used in pig feeding.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7827012
TI  - The effect of condensed tannins in Lotus corniculatus on plasma metabolism of
      methionine, cystine and inorganic sulphate by sheep.
AB  - Fresh Lotus corniculatus containing 27 g extractable condensed tannin (CT)/kg dry
      matter (DM) and 8 g bound CT/kg DM was fed at hourly intervals to sheep held in
      metabolism cages to study the effects of CT on nutrient digestion and on
      metabolism of methionine, cystine and inorganic sulphate in plasma. Polyethylene
      glycol (PEG) was continuously infused into the rumen of half the sheep to remove
      the effects of CT. Principal measurements in the two groups were plasma
      irreversible loss (IRL) rate and interconversions of methionine, cystine and
      inorganic sulphate using 35S labelling. CT in Lotus corniculatus had no effects
      on the apparent digestion of cellulose and minerals, slightly depressed DM,
      organic matter and hemicellulose digestion and markedly reduced the apparent
      digestion of N (P < 0.01). The concentration of NH3 and molar proportions of iso
      butyric acid, iso-valeric acid and n-valeric acid in rumen fluid were markedly
      increased by the PEG infusion (P < 0.01), whereas total volatile fatty acid
      concentration and molar proportions of acetic acid, propionic acid and n-butyric
      acid were not affected. PEG infusion temporarily increased rumen protozoa
      numbers. CT greatly increased the IRL of plasma cystine (13.1 v. 7.0 mumol/min; P
      < 0.05) and reduced IRL of plasma inorganic sulphate (36.8 v. 48.1 mumol/min; P <
      0.01) but had no effect on methionine IRL. CT increased transulphuration of
      methionine to cystine (4.37 v. 1.24 mumol/min; P < 0.05), increased cystine
      entering the plasma from whole-body protein turnover plus absorption from the
      small intestine (9.34 v. 5.75 mumol/min; P < 0.05) and increased cystine flux to
      body synthetic reactions (11.89 v. 5.41 mumol/min; P < 0.05). CT had no effect on
      the proportion of methionine total flux transferred to sulphate (0.05 v. 0.06; P
      < 0.05), reduced the proportion of methionine flux transferred to body synthetic
      reactions (0.68 v. 0.86) and markedly reduced the proportion of cystine flux
      transferred to sulphate (0.09 v. 0.27; P < 0.01). It was concluded that CT in
      Lotus corniculatus reduced rumen protein degradation and markedly increased
      utilization of plasma cystine for body synthetic reactions.

PMID- 7827013
TI  - One-month regular oral nutrition in alcoholic cirrhotic patients. Changes of
      nutritional status, hepatic function and serum lipid pattern.
AB  - The effect of a regular oral diet supplying 167 kJ/kg per d (40 kcal/kg per d) on
      nutritional state, liver function and serum lipid profile was assessed in thirty
      severely malnourished alcoholic cirrhotic inpatients. Their diet was monitored by
      a trained dietitian and they were vigorously encouraged to eat all meals served.
      One month after their entry into the study, protein and energy intakes were
      significantly higher (P < 0.001) in keeping with an improvement of their
      nutritional status as evaluated by means of height-creatinine index, muscular mid
      arm circumference, tricipital skinfold thickness (P < 0.01 for all) and fat mass
      (P < 0.001). Assessment of liver function tests showed that levels of aspartate
      aminotransferase (EC 2.6.1.1), gamma-glutamyl transferase (EC 2.3.2.2) and
      bilirubin decreased (P < 0.05, P < 0.02 and P < 0.05 respectively) while
      prothrombin time values increased (P < 0.05). Similarly, serum albumin increased
      modestly while transthyretin did not change. Orosomucoid and C-reactive protein
      decreased (P < 0.001 and P < 0.01 respectively), indicating an improvement of the
      inflammatory state. Apolipoprotein A1 and high-density-lipoprotein (HDL)
      cholesterol correlated with several tests of liver function and improved
      significantly during the study period (P < 0.001 and P < 0.02 respectively).
      Moreover, changes in cholesterol and HDL-cholesterol correlated with those in
      transthyretin (P < 0.02 and P < 0.05 respectively). The changes in ApoA1 and HDL
      cholesterol were greater in patients whose fat mass increased significantly. Our
      findings show that adequate oral nutrition resulted in a better nutritional
      status in cirrhotics after 1 month of hospitalization. The serum lipid variables
      appeared to be more useful indicators of functional liver improvement than the
      classic liver function tests which rather indicate liver damage.

PMID- 7827014
TI  - Polyols, breath hydrogen and fermentation.

PMID- 7827015
TI  - Bioavailability '93: different aspects of 'bioavailability' in perspective.

PMID- 7827016
TI  - Salt dependence of calicheamicin-DNA site-specific interactions.
AB  - Calicheamicin gamma 1I site-specifically binds and cleaves three closely spaced
      tetranucleotide sequences embedded in an AT-rich region of a 142 base pair DNA
      restriction fragment. Cleavage is observed predominantly at the TCCT, TTGT, and
      ATCT sequences, of which TCCT is the primary cleavage site. The Gibbs free
      energies required to bind calicheamicin to these sequences within the DNA
      restriction fragment have been determined as a function of NaCl concentration at
      pH 8.1 and 0 degrees C and at pH 7.5 and 23 and 0 degrees C. Between 150 mM and 1
      M NaCl, calicheamicin binding to all three sequences is insensitive to salt. The
      insensitivity of calicheamicin binding to salt continues to 50 mM NaCl for the
      TTGT and ATCT sequences; the delta G values for calicheamicin binding to these
      sequences are on the order of -7.8 to -7.9 kcal mol-1 over the entire range of
      NaCl concentrations studied. However, between 150 and 125 mM NaCl, the TCCT
      sequence displays a sharp transition in the delta G of calicheamicin binding from
      -7.6 to -8.9 kcal mol-1. Below 125 mM NaCl, the delta G values for calicheamicin
      binding to the TCCT sequence again are invariant. An analysis of the data in
      terms of polyelectrolyte theory suggests that counterion release from DNA does
      not contribute significantly to the energetics of the association and that the
      association of calicheamicin with specific DNA sequences is dominated by nonionic
      rather than electrostatic forces. Our results further suggest that some
      calicheamicin binding/cleavage sites are dependent on flanking sequences.

PMID- 7827017
TI  - Contribution of individual tryptophan residues to the fluorescence spectrum of
      native and denatured forms of human carbonic anhydrase II.
AB  - Measurements were made of fluorescence spectra produced by pseudo-wild-type human
      carbonic anhydrase II and mutants in which the tryptophan residues had been
      replaced by phenylalanine or cysteine residues. 2D NMR spectra of 15N-labeled
      proteins indicated that the mutations had essentially no long range effects on
      structure and that the pertubations of structure in the vicinity of the mutated
      Trp were small. The individual contributions of the seven tryptophan residues
      were deduced from measurements on native proteins and on proteins subjected to
      various denaturing conditions. Trp97 and Trp245 are the major fluorescence
      emitters in the native state, contributing 52% and 38%, respectively, to the
      total fluorescence intensity. Comparisons of the fluorescence yield of pseudo
      wild-type human carbonic anhydrase II and mutant proteins also indicate net
      energy transfer from Trp16 to Trp5 and from Trp192 to Trp209. The fluorescence
      from Trp5 is efficiently quenched by His64. In addition, acrylamide quenching of
      fluorescence was used to probe the environment of tryptophans in proteins
      incubated in 0, 1.5, and 5 M guanidine hydrochloride. The results indicate that
      the part of the native protein that corresponds to beta-strands 3-7 forms a
      compact core in a molten globule intermediate.

PMID- 7827018
TI  - Crystal structure of C-T-C-T-C-G-A-G-A-G. Implications for the structure of the
      Holliday junction.
AB  - The structure of the B-DNA decamer of sequence C-T-C-T-C-G-A-G-A-G shows a
      crossed arrangement of helices in the C2 crystal lattice. This is the fourth
      example of a crossed arrangement of B-DNA oligomers in a crystal, and in spite of
      the fact that each of these four crystallizes in a different lattice, all have
      nearly identical structures at the crossing contact. This ubiquitous crossing
      arrangement may be used to generate a structure for the Holliday junction that is
      fully consistent with the available physical data.

PMID- 7827019
TI  - Role of glycine residues in the structure and function of lactose permease, an
      Escherichia coli membrane transport protein.
AB  - By using oligonucleotide-directed, site-specific mutagenesis, the role of 34 Gly
      residues in the lactose permease of Escherichia coli has been studied
      systematically. Each of 34 out of a total of 36 Gly residues was replaced with
      Cys in a functional permease mutant devoid of Cys residues (C-less permease), as
      previous experiments demonstrate that Gly-402 and Gly-404 can be deleted by
      truncation of the C-terminus with no loss of activity [Roepe, P. D., et al.
      (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 3992; McKenna, E., et al. (1991) Proc.
      Natl. Acad. Sci. U.S.A. 88, 2969]. Out of the 34 Cys-replacement mutants
      described, 15 transport lactose with high activity, 16 exhibit decreased but
      significant ability to catalyze lactose accumulation, and 3 (Gly-64-->Cys, Gly
      115-->Cys and Gly-147-->Cys) exhibit no activity whatsoever. The inactive mutants
      were studied in more detail by replacement of Gly with Ala, Val, or Pro. C-less
      permease with Gly-115-->Ala or Gly-147-->Ala transports lactose almost as well as
      the control, while mutants with Val or Pro in place of Gly have little or no
      capacity to accumulate the disaccharide. In contrast, mutants with Ala, Val, or
      Pro in place of Gly-64 are inactive. Strikingly, however, when the mutations are
      placed in the wild-type background, Gly-64-->Ala permease transports lactose,
      beta,D-galactopyranosyl 1-thio-beta,D-galactopyranoside, and methyl 1-thio-beta,D
      galactopyranoside 40-60% as well as wild-type permease, while Gly-64-->Val or Gly
      64-->Pro permease is inactive toward all of these substrates. The results
      indicate that although none of the Gly residues in lactose permease is mandatory
      for activity, the bulk of the side chain at positions 64, 115, and 147, rather
      than conformational flexibility at these positions, is particularly important.

PMID- 7827020
TI  - Chimeric human calcitonin and glucagon receptors reveal two dissociable
      calcitonin interaction sites.
AB  - Two chimeric receptors were constructed by transposing the coding regions for the
      putative N-terminal domains of the human calcitonin (hCTR) and glucagon (hGGR)
      receptors. These receptors were stably expressed as glycosylated proteins with
      molecular masses of 80 kDa for the calcitonin receptor N-terminus chimera (NtCTr)
      and 65 kDa for the glucagon receptor N-terminus chimera (NtGGr). The NtCTr
      chimera binds salmon calcitonin (sCT) with an apparent Kd of 12 nM relative to
      0.3 nM for the native hCTR. However, this chimera does not mediate a cAMP
      response even with a transfectant expressing 1.8 x 10(6) cell surface receptors.
      Stable transfectants expressing the NtGGr chimera show no detectable binding of
      125I-sCT or 125I-human glucagon. Surprisingly, adenylate cyclase is activated
      through the NtGGr chimera by sCT, pCT, and hCT with half-maximal activation at
      2.2 +/- 0.6, 5.8 +/- 2.1, and 810 +/- 151 nM, respectively, and the maximum
      response is similar to that induced by 25 microM forskolin. The rank-order of
      competition for sCT binding to the NtCTr chimera is similar to the hCTR (sCT >
      pCT > hCT), but the concentrations required for half-maximal competition are 100-
      to > 2000-fold higher. In addition, salmon calcitonin binds with a much more
      rapid on-rate and off-rate to the NtCTr chimera relative to the hCTR which binds
      hormone irreversibly. Cross-linking of 125I-sCT to the NtCTr chimera with
      bis(sulfosuccinimidyl) suberate is much greater than to the hCTR, suggesting
      unique conformations for the two receptor-hormone complexes.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7827021
TI  - Conformational studies on plasminogen activator inhibitor (PAI-1) in active,
      latent, substrate, and cleaved forms.
AB  - Plasminogen activator inhibitor 1 (PAI-1), the primary physiological inhibitor of
      t-PA, is an unusual member of the serpin family of serine protease inhibitors, in
      that it spontaneously converts to a latent form. Latent PAI-1 has been reported
      to share characteristics with the cleaved form of other serpins. Here we examine
      the conformation of four forms of PAI-1, active and latent wild-type, together
      with a noninhibitory, substrate mutant that is cleavable at P1-P1', and its
      cleaved product. The circular dichroism spectra of active and latent PAI-1 showed
      differences consistent with decreased alpha-helix from 26% to 22% and increased
      beta-sheet from 23% to 34% as active-->latent. Active and substrate PAI-1 were
      less thermostable than latent PAI-1, which was 50% denatured at 70 degrees C. In
      contrast, cleaved PAI-1 was very stable, with little loss of structure at 100
      degrees C. Cleaved PAI-1 was much more resistant to guanidinium chloride (Gdn
      HCl), 50% unfolding requiring 4.5 M Gdn-HCl, while active, latent, and substrate
      forms of PAI-1 were 50% unfolded in 2-2.5 M Gdn-HCl. The differences in
      fluorescence emission maxima, latent 339 nm, active 336 nm, substrate 343 nm, and
      cleaved 333 nm, underline the contrast between latent and cleaved PAI-1. The
      conformational changes occurring on cleavage are clearly more profound than those
      seen on transition from active to latent PAI-1.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7827022
TI  - ADP-ribosylation of alpha i3C20 by the S1 subunit and deletion peptides of S1 of
      pertussis toxin.
AB  - Recombinant S1 subunit of PT (rS1) and two carboxyl-terminal deletion peptides,
      C180 and C204, which comprise the amino-terminal 180 and 204 amino acids of S1,
      respectively, were analyzed for the ability to ADP-ribosylate alpha i3C20, a
      synthetic peptide composed of the 20 carboxyl-terminal amino acids of the alpha
      subunit of the heterotrimeric G protein Gi3. Under linear velocity conditions,
      C180 ADP-ribosylated alpha i3C20 at a 3-fold higher rate than either C204 or rS1.
      At variable NAD, rS1, C204, and C180 ADP-ribosylated alpha i3C20 with similar
      initial velocities which followed Michaelis-Menten kinetics. In contrast, at
      variable alpha i3C20, rS1, C204, and C180 ADP-ribosylated alpha i3C20 with
      different initial velocities. At variable alpha i3C20, C204- and rS1-catalyzed
      ADP-ribosylation followed Michaelis-Menten kinetics, while the velocity curve
      generated by C180 diverged from Michaelis-Menten kinetics. The rates of initial
      velocity of C180 did not fit the Lineweaver-Burk equation, but could be
      transformed into the Hill equation which yielded a Hill coefficient of 2. This
      predicted that C180 possessed cooperativity between the two substrate binding
      sites. Other experiments showed that C180 ADP-ribosylated alpha i3C20 at 60% of
      the rate for the ADP-ribosylation of Gt. These data showed that the entire
      catalytic mechanism for ADP-ribosylation resides within the first 180 amino acids
      of S1 and that the carboxyl-terminal 55 residues of S1 allow the ADP-ribosylation
      of alpha i3C20 to proceed via Michaelis-Menten kinetics. These data along with
      earlier studies (Krueger & Barbieri, 1993) were also consistent with the presence
      of two Gt protein binding sites within S1.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7827023
TI  - New inhibitors of the quinol oxidation sites of bacterial cytochromes bo and bd.
AB  - A screen has been performed of possible inhibitors of the quinol oxidation sites
      of the two terminal oxidases of Escherichia coli, cytochromes bo and bd. Aurachin
      C and its analogues were found to be particularly effective inhibitors of both
      enzymes, whereas aurachin D and its analogues displayed a selectivity for
      inhibition of cytochrome bd. In addition, a tridecyl derivative of stigmatellin
      was found to inhibit cytochrome bo at concentrations which were without
      significant effect on cytochrome bd. Titration of membrane-bound cytochromes bo
      and bd with aurachin C gave an observed dissociation constant in the range of 10(
      8) M. A similar observed dissociation constant was determined for aurachin D
      inhibition of cytochrome bd. For both enzymes, their kinetic behavior during a
      series of substrate pulses indicates that it is reduction of the enzyme by
      quinol, and not reaction with oxygen, which is inhibited. It is concluded that
      the aurachins are powerful inhibitors of the quinol oxidation sites of bacterial
      cytochromes bo and bd. The effects of aurachin C on cytochrome bo were
      investigated in more detail. The number of inhibitor binding sites on the
      purified enzyme was determined by titration to be 0.6 per enzyme. At an
      inhibitor/oxidase ratio of 1.0, electron donation into the enzyme from added
      quinol is extremely slow, making it very unlikely that there is more than one
      quinone-reactive site. Aurachin C caused a potent inhibition of electron donation
      from a pulse of quinol.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7827024
TI  - The role of the ganglioside GD1a as a receptor for Sendai virus.
AB  - The ganglioside GD1a, which serves as a receptor for Sendai virus, also affects
      lipid polymorphism as determined by 31P nuclear magnetic resonance. The
      ganglioside promotes the formation of isotropic structures in
      monomethyldioleoylphosphatidylethanolamine. GD1a also raises the bilayer to
      hexagonal phase transition temperature of this lipid. The effects of GD1a on the
      kinetics of viral fusion can be understood on the basis of its role in
      facilitating the binding of Sendai virus to target membranes as well as its
      effects on membrane physical properties. Fusion of Sendai virus with liposomes
      composed of egg phosphatidylethanolamine is particularly sensitive to the
      presence of ganglioside. In the absence of ganglioside no fusion is observed due
      to the absence of virus binding to the target membrane. Between 2 and 6 mol %
      GD1a in egg phosphatidylethanolamine liposomes there is a marked increase in the
      rate constant of binding of the virus to the liposome but a decrease in the
      fusion rate constant. The latter effect is found to be common to a number of
      other amphiphiles that raise the bilayer to hexagonal phase transition
      temperature. The ganglioside enhances virus binding to liposomes of all the
      compositions studied, but leakage rates and fusion rate constants are either
      unaffected or reduced. In the systems studied, the enhanced formation of
      isotropic structures in liposomes containing the ganglioside does not enhance the
      kinetics of the actual fusion reaction.

PMID- 7827025
TI  - Osmotic properties of the calcium-regulated actin filament.
AB  - The diameter of the actin filament decreases with an increase of the protein
      osmotic pressure. This phenomenon is accompanied by a decrease of the angle
      (alpha) formed between the long axis of the actin monomer and the pointed end of
      the filament axis. At 1.8 x 10(5) dyn/cm2 (the protein osmotic pressure in frog
      muscle) the diameter is 8.34 nm and the angle (alpha) is 61.5 degrees. The
      interfilament distance of tropomyosin-decorated actin filaments, at a set of
      different osmotic pressures, is larger than that of F-actin filaments. This
      suggests that the two tropomyosin helices project out of the contour of the actin
      filament. The tropomyosin-decorated actin filament is more rigid than F-actin. At
      1.8 x 10(5) dyn/cm2, the angle (alpha) is 76.4 degrees, as compared to the value
      of 61.5 degrees for F-actin. The interfilament distance of troponin-tropomyosin
      decorated actin filaments is sensitive to Ca2+: in the physiological range of
      protein osmotic pressure it decreases from 13.3 nm, in the presence of 2 mM EGTA,
      to 12.2 nm in the presence of 0.2 mM CaCl2. Two alternative models are proposed
      to explain the decrease in interfilament distance. (a) Calcium shifts tropomyosin
      along the actin monomer, toward the filament axis (the classical model). (b)
      Calcium releases the rigidity of the tropomyosin-decorated filament and restores
      the original plasticity of F-actin. The consequent decrease of the angle (alpha)
      brings the tropomyosin helices nearer to the filament axis, without any real
      movement of tropomyosin along the actin monomer.

PMID- 7827026
TI  - Purification and low temperature spectroscopy of gecko visual pigments green and
      blue.
AB  - We purified two kinds of visual pigments, gecko green and gecko blue, from
      retinas of Tokay geckos (Gekko gekko) by two steps of column chromatography, and
      investigated their photobleaching processes by means of low temperature
      spectroscopy. Absorption maxima of gecko green and blue solubilized in a mixture
      of 3-[(3-cholamidopropyl)dimethylammonio]-1- propanesulfonate (CHAPS) and
      phosphatidylcholine were 522 and 465 nm, respectively, which are close to those
      observed in the photoreceptor cells. Low temperature spectroscopy identified six
      intermediates in the photobleaching process of gecko green; batho (lambda max =
      569 nm), BL (lambda max = 519 nm), lumi (507 nm), meta I (approximately 486 nm),
      meta II (approximately 384 nm), and meta III intermediates (approximately 500
      nm). In contrast to the high similarity in amino acid sequence between gecko
      green and iodopsin [Kojima, D., et al. (1992) Proc. Natl. Acad. Sci. U.S.A. 89,
      6841-6845], the batho-green did not revert thermally to original gecko green but
      converts to the next intermediate. The photobleaching process of gecko blue was
      investigated by low temperature spectroscopy, and three intermediates, meta I
      (lambda max = approximately 470 nm), meta II (lambda max = approximately 370 nm)
      and meta III (lambda max = approximately 475 nm), were identified. A comparative
      study on the thermal behavior of meta intermediates revealed that the thermal
      stability of meta II intermediate of both of the gecko visual pigments is lower
      than that of metarhodopsin II. The result supports the idea that both the gecko
      visual pigments are cone-type ones.

PMID- 7827027
TI  - Stoichiometry for the elongation factor Tu.aminoacyl-tRNA complex switches with
      temperature.
AB  - In bacterial protein synthesis binding of an aminoacyl-transferRNA (aa-tRNA) to
      the ribosomal acceptor site (A-site) is catalyzed by elongation factor Tu (EF
      Tu). Two guanosine triphosphates (GTPs) are hydrolyzed on EF-Tu for every bound
      aa-tRNA. This was rationalized by the notion of an extended ternary complex,
      consisting of two EF-Tu.GTPs bound to a single aa-tRNA. In this work, we combine
      fast kinetics with RNase A protection experiments to measure the stoichiometry
      between EF-Tu.GTP and aa-tRNA at 37 degrees C, where the binding is weak. We find
      a 2:1 stoichiometry between EF-Tu.GTP and aa-tRNA at 37 degrees C, but at 0
      degree C, under otherwise similar conditions, the stoichiometry of the complex is
      close to 1:1. These results suggest alternative pathways for aa-tRNA binding to
      ribosomes, since two GTPs are hydrolyzed per peptide bond at both temperatures.
      At 37 degrees C, aa-tRNA enters the A-site in a pentameric complex with two EF
      Tu's on which two GTPs are hydrolyzed in synchrony, when cognate codon-anticodon
      contact is established. This pentameric model also explains how two GTPs can be
      hydrolyzed on EF-Tu, without rejection of 50% of the cognate aa-tRNAs in
      proofreading. At 0 degree C, in contrast, two ordinary ternary complexes may form
      a pentameric complex on, rather than off, the ribosome. When the two EF-Tu bound
      GTPs are hydrolyzed, one aa-tRNA enters the A-site, and the other dissociates to
      the free state.

PMID- 7827028
TI  - Detection of a catalytic antibody species acylated at the active site by
      electrospray mass spectrometry.
AB  - The chemical interactions between a catalytic antibody Fv fragment and ester
      substrates were examined using pneumatically assisted electrospray (ion spray)
      mass spectrometry. Upon addition of the p-nitrophenyl ester substrate to the
      antibody fragment, an antibody fragment species that represents approximately 8%
      of the total Fv concentration is clearly observed in the electrospray spectrum.
      The observed increase in molecular weight of the Fv fragment corresponds to the
      mass of the acyl group of the substrate. Formation of the acyl-Fv species is
      blocked by preincubation of the antibody fragment with hapten inhibitor,
      suggesting that the acyl linkage involves a residue in the active site of the
      antibody. The acyl-Fv species is not observed when the corresponding p
      chlorophenyl ester substrate is used, indicating that the level of this species
      is dependent on the leaving group of the substrate. The acylated species is not
      observed for a site-directed mutant lacking catalytic activity, His L91 Gln. The
      present results are consistent with modeling studies of the structure of the Fv
      fragment and provide strong confirmatory evidence for the multistep kinetic
      mechanism previously proposed for this antibody.

PMID- 7827029
TI  - Prolines and amyloidogenicity in fragments of the Alzheimer's peptide beta/A4.
AB  - Although it is well accepted that the structure of amyloid fibrils is dominated
      by some form of antiparallel beta-sheet, there are few details on the secondary
      structural arrangements of the constituent peptides and how these peptides pack
      together in the fibril. We describe here the use of scanning proline mutagenesis
      to map the secondary structural roles of each residue in amyloidogenic peptide
      fragments of the Alzheimer's amyloid peptide beta/A4. In two series of fragments
      related to residues 15-23 and 12-26 of beta/A4, we show that Pro replacement of
      any residue in the amyloidogenic sequence LVFFAED, corresponding to residues 17
      23, leads to essentially complete loss of fibril formation and to excellent
      peptide solubility. Since peptidyl-prolyl bonds are incapable of forming standard
      extended chain conformations, the results suggest that residues 17-23 make up the
      beta-sheet core of the fibrils formed by these fragments. In contrast to the
      proline replacements, alanine substitutions at residues 17, 18, and 20 have no
      effect on fibril formation, while replacement of Phe19 reduces fibril formation
      to 15% of the level found for the wild type sequence. Scanning proline
      mutagenesis should play a useful role in mapping the secondary structural
      features of larger amyloidogenic peptide sequences, including longer,
      physiologically relevant forms of beta/A4. In addition, these results suggest
      explanations for some amyloidogenic effects observed in disease-related peptides
      and also suggest a possible role for aggregation-inhibiting insertion of prolines
      in protein evolution and protein design.

PMID- 7827030
TI  - Engineering of fibroblast growth factor: alteration of receptor binding
      specificity.
AB  - A five-residue loop structure in basic fibroblast growth factor (FGF-2) which
      extends from amino acid residue 118 to residue 122 was replaced, by cassette
      mutagenesis, with the corresponding seven-residue loop structure from the
      structural homologue acidic fibroblast growth factor (FGF-1) or the corresponding
      five-residue loop from interleukin-1 beta to give FGF-2LA and FGF-2LI,
      respectively. The mutants were expressed in Escherichia coli and purified to
      homogeneity, and their heparin and receptor binding and biological properties
      were examined. The ability of FGF-2LA to induce endothelial cell proliferation
      was the same as that of FGF-2. Affinities of the mutants to heparin and to cells
      that express FGF receptor-1 (FGFR-1) were identical to those of the wild-type
      protein. The role of the loop structure in FGF-1 and FGF-2 was elucidated by
      using soluble FGF receptor systems, which display distinct ligand binding
      specificities. Thus, FGF-2LA bound, with the same affinity as FGF-1 and FGF-2, to
      FGFR-1 and FGFR-2, whereas only FGF-1 and the FGF-1 loop-containing mutant, FGF
      2LA, bound to the keratinocyte growth factor receptor. A change in receptor
      binding specificity was not observed with the FGF-2LI engineered mutant. That the
      binding specificity of FGF-2 was dramatically altered by transfer of a loop
      structure from FGF-1 to resemble the binding profile of the donor protein
      provides strong evidence that this motif is a receptor binding specificity
      determinant of fibroblast growth factors.

PMID- 7827031
TI  - Monomeric base damage products from adenine, guanine, and thymine induced by
      exposure of DNA to ultraviolet radiation.
AB  - The formation of monomeric products in DNA upon exposure to UV radiation was
      investigated. Three novel products were identified in DNA in aqueous solution
      upon exposure to UV radiation at 254 nm in a dose range from 100 to 10,000 J/m2.
      These were 4,6-diamino-5-formamidopyrimidine, 2,6-diamino-4-hydroxy-5
      formamidopyrimidine, and 5-hydroxy-5,6-dihydrothymine. These three products are
      known to be substrates for base excision repair enzymes involved in the reversal
      of oxidative DNA damage. The dependence of the yields of formamidopyrimidines on
      UV radiation dose was nonlinear, whereas the yield of 5-hydroxy-5,6
      dihydrothymine was increased linearly in the entire dose range. Of these
      products, 4,6-diamino-5-formamidopyrimidine was the only compound produced in
      appreciable amounts at 310 nm. At the highest dose used, the formation of other
      pyrimidine- and purine-derived products was also observed. Their amounts,
      however, were increased above control levels up to 2-fold only. The hydroxyl
      radical scavenger dimethyl sulfoxide had no effect on product yields excluding
      the involvement of hydroxyl radical in product formation. 4,6-Diamino-5
      formamidopyrimidine and 2,6-diamino-4-hydroxy-5-formamidopyrimidine may be
      produced by hydration of adenine and guanine, respectively, across the N(7)-C(8)
      double bond by mechanisms similar to those proposed previously for well-known
      formation of pyrimidine hydrates with the hydroxyl group located at C(6).
      Formation of 5-hydroxy-5,6-dihydrothymine indicates that hydration of thymine
      with the hydroxyl group located at C(5) of the pyrimidine ring also
      occurs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7827032
TI  - Mechanism-based inactivation of phosphotriesterase by reaction of a critical
      histidine with a ketene intermediate.
AB  - Five alkynyl phosphate esters have been synthesized as probes of the active site
      structure of phosphotriesterase. These compounds have the potential to be
      converted by the enzyme to a highly reactive ketene intermediate which can then
      react with an active site nucleophile causing irreversible inhibition of the
      enzyme by formation of an inactive covalent adduct. All five compounds completely
      inactivate enzyme function in less than 15 s at pH 7.0. The partition rations of
      1-hexynyl diethyl phosphate (I), 1-propynyl diethyl phosphate (II), 1-hexynyl
      diphenyl phosphate (III), 1-hexynyl dimethyl phosphate (IV), and ethynyl diethyl
      phosphate (V) fall in the range between 480 and 1700; thus, all five alkynyl
      phosphate esters work equally well as inactivators despite the differences in
      their structures. The rate constants for enzyme inactivation, kinact, are 1.7 s-1
      with I, 1.3 s-1 with II, and 0.12 s-1 with IV. They compare well with the kcat
      for the Co-substituted phosphotriesterase; hence these compounds are good
      substrates. The stoichiometry of inhibitor bound to protein is 1:1, as determined
      by inactivation of the enzyme using the radiolabeled compound [3-14C]-1-propynyl
      diethyl phosphate. Addition of an exogenous nucleophile, azide, did not protect
      phosphotriesterase from being inactivated by the alkynyl phosphate esters,
      suggesting that the reactive intermediate produced from the inhibitor is not
      released from the enzyme surface prior to covalent labeling of the protein.
      Chemical and spectroscopic evidence suggests that a histidine residue is modified
      in the inactivation reaction. The inactivated phosphotriesterase can be
      reactivated by increasing the pH of the protein solution. N-Acylimidazoles are
      known to be easily hydrolyzed at alkaline pH values.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7827033
TI  - Histidine-254 is essential for the inactivation of phosphotriesterase with the
      alkynyl phosphate esters and diethyl pyrocarbonate.
AB  - The alkynyl phosphate ester, 1-hexynyl diethyl phosphate (I), is a mechanism
      based inhibitor of phosphotriesterase. It has been previously determined that a
      histidine residue in the wild-type phosphotriesterase is covalently modified by
      this compound. In order to identify which of the seven histidine residues in the
      native enzyme are required for inactivation, the kinetic properties of
      phosphotriesterase mutants with this suicide substrate were examined in detail.
      Six of the seven mutants (histidine to asparagine) were rapidly inactivated by I.
      The mutants H55N, H57N, and H230N also showed partition ratios that were lower
      than for the wild-type enzyme. The rate of inactivation of H201N was
      significantly slower than that of wild-type phosphotriesterase. The H254N mutant
      could not be inactivated; no more than 60% of the initial activity was lost, even
      at I/E0 ratios of 4000:1. These results suggest that His-254 is essential for the
      inactivation of phosphotriesterase and is likely to be the primary target in the
      wild-type enzyme for modification by I. The inactivation of wild-type
      phosphotriesterase and the seven mutants was also studied using diethyl
      pyrocarbonate, a histidine selective reagent. The second-order rate constant for
      the inactivation of wild-type phosphotriesterase was determined to be 1.3 M-1 min
      1. The rate constants for the inactivation of the H55N, H57N, H201N, and H230N
      mutants were larger than for the wild-type enzyme. Thus, it appears that when
      these histidine residues are replaced by asparagine, other histidine residues in
      the active site become more susceptible to modification, resulting in a faster
      rate of inactivation. The mutant H254N was not inactivated in the presence of
      DEPC.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7827034
TI  - Role of electrostatic screening in determining protein main chain conformational
      preferences.
AB  - Amino acids display significant variation in propensity for the alpha R-helical,
      beta-sheet, and other main chain conformational states in proteins and peptides.
      The physical reason for these preferences remains controversial. Conformational
      entropy, steric factors, and the hydrophobic effect have all been advanced as the
      dominant underlying cause. In this work, we explore the role of a fourth factor,
      electrostatics, in determining the main chain conformation in protein molecules.
      Potentials of mean force derived from experimental protein structures are used to
      evaluate the free energy of electrostatic and other interactions of a residue in
      a protein environment. The local and nonlocal electrostatic interactions of main
      chain polar atoms are found to be crucial for determining the preferences of
      residues for the alpha R-helical state and other main chain conformational states
      of a residue. Further, the strength of local and nonlocal electrostatic
      interactions is shown to depend on the electrostatic screening by solvent and
      protein groups. Residue specific modulation of this screening in a manner related
      to side chain bulk and squatness produces a model that fits the observed
      distribution of residue conformations in proteins and recent experimental
      mutagenesis data on protein stability better than any other single factor.

PMID- 7827035
TI  - Incorporation of 2'-deoxy-6-thioguanosine into G-rich oligodeoxyribonucleotides
      inhibits G-tetrad formation and facilitates triplex formation.
AB  - An efficient and expeditious method for the synthesis of S6-(cyanoethyl)-N2
      isobutyryl (or trifluoroacetyl)-2'-deoxy-6-thioguanosine (7 and 2) from 2'
      deoxyguanosine (G) has been developed. Compound 7 has been incorporated into
      several G-rich triple-helix-forming oligonucleotides (TFOs) using solid-support,
      phosphoramidite chemistry. The purified oligonucleotides containing 2'-deoxy-6
      thioguanosine (S6-dG) residues in the place of G have been characterized by
      nucleoside composition analysis. These modified TFOs have been shown to be stable
      in aqueous, as well as buffered, solutions normally used to assay triple-helix
      formation. It has also been demonstrated that partial incorporation of S6-dG is
      effective in inhibiting the formation of G tetrads in G-rich
      oligodeoxyribonucleotides, thus facilitating triple-helix formation in potassium
      containing buffers.

PMID- 7827036
TI  - Structure of the isolated catalytic domain of diphtheria toxin.
AB  - The structure of the isolated catalytic domain of diphtheria toxin at pH 5.0 was
      determined by X-ray crystallography at 2.5 A resolution and refined to an R
      factor of 19.7%. The domain is bound to its endogenous inhibitor adenylyl(3'-
      >5')uridine 3'-monophosphate (ApUp). The structure of this 190-residue domain,
      which was expressed in and isolated from Escherichia coli, is essentially
      identical to the structure of the catalytic domain within whole diphtheria toxin
      determined at pH 7.5. However, there are two adjacent surface loops (loop 66-78
      and loop 169-176) that exhibit clear differences when compared to the structure
      of the catalytic domain in whole diphtheria toxin. Although both loops are at the
      surface of the protein and are relatively flexible, the chain trace is well
      defined in the electron density. The main structural difference is the closer
      approach of loops 66-78 and 169-176. We ascribe this structural change mainly to
      the absence of the neighboring transmembrane domain in the isolated catalytic
      domain as compared to whole diphtheria toxin. We suggest that this change
      represents the first step of the structural transition from the catalytic domain
      in whole diphtheria toxin to the translocated form of the domain. The changes are
      described in detail, and their implications for membrane translocation are
      discussed.

PMID- 7827037
TI  - Structure and function analysis of Escherichia coli inorganic pyrophosphatase: is
      a hydroxide ion the key to catalysis?
AB  - Using site-directed mutagenesis, we have completed replacing all 17 putative
      active site residues of Escherichia coli inorganic pyrophosphatase (PPase). We
      report here the production of 11 new variant proteins and their initial
      characterization, including thermostability, hydrophobicity, oligomeric
      structure, and specific activity at pH 8. Studies of the pH-rate profiles of 12
      variants containing substitutions for potentially essential residues showed that
      the effect of the mutation was always to increase the pKa of a basic group
      essential for both substrate binding and catalysis by 1-3 pH units. The D70E
      variant had the lowest activity at all pHs; the K29R, R43K, and K142R variants
      also had low kcat/Km values. The principal effect seen in the other variant
      proteins was higher and sharper pH optima; their pH-independent kcat and kcat/Km
      values changed at most by a factor of 8. Our results suggest that the most likely
      candidate for the essential basic group affected by all mutations in the active
      site is a hydroxide ion stabilized by coordination to the essential Mg2+ ions.
      Analyzing our results using the structure recently obtained for E. coli PPase
      [Kankare et al. (1994) Protein Eng. 7, 823-830] led us to identify a group of
      residues, centered around Asp70 and including Tyr55, Asp65, Asp67, Asp102, and
      Lys104, that we believe binds the magnesium ions that are critical for the
      activity, possibly by stabilizing the essential hydroxide. Others, including
      Lys29, Arg43, and Lys142, are more spread out and more positively charged. They
      appear to be involved in binding substrate and product. Tyr55 is also a key part
      of the hydrophobic core of E. coli PPase; when it or residues that interact with
      it are conservatively mutated, there are changes in the overall structure of the
      enzyme as assayed by thermostability, hydrophobicity, or oligomeric structure.

PMID- 7827038
TI  - Effect of D97E substitution on the kinetic and thermodynamic properties of
      Escherichia coli inorganic pyrophosphatase.
AB  - Aspartic acid 97 in the inorganic pyrophosphatase of Escherichia coli (E-PPase)
      has been identified as an evolutionarily conserved residue forming part of the
      active site [Cooperman et al. (1992) Trends Biochem. Sci. 17, 262-266]. Here we
      determine the effect of D97E substitution on several kinetic and thermodynamic
      properties of E-PPase, including rate and equilibrium constants for enzyme
      catalyzed PPi.Pi equilibration at pH 7.2 and 8.0, Mg2+ affinity in the presence
      and absence of substrate, and the Mg2+ and pH dependence of kcat and Km. We find
      the major effects of D97E substitution are to (a) decrease markedly the pH
      independence rates of both PPi hydrolysis and, especially, PPi resynthesis on the
      enzyme, (b) selectively destabilize both the EMg4PPi complex and the transition
      state between this complex and the EMg2(MgPi)2 complex, (c) raise the pKa of the
      basic group "essential" for PPi hydrolysis and for productive PPi binding by 1.5
      and > 2.2 log units, respectively, (d) distort a site to which Mg2+ binds in the
      absence of substrate such that occupancy of the site by Mg2+ no longer confers
      enzymatic activity, and (e) decrease the affinity of one of the two Mg2+ ions
      that binds to enzyme in the presence of substrate. That this multiplicity of
      effects arises from a single Asp to Glu substitution suggests, in the absence of
      any evidence for a generalized structural change, a tightly integrated active
      site in which the perturbation induced by conservative substitution at a single
      location can have widespread functional effects.

PMID- 7827039
TI  - Bromoacetamido analogs of indomethacin and mefenamic acid as affinity-labeling
      agents and mechanistic probes for prostaglandin H2 synthase.
AB  - Affinity-labeling agents, 1-[4-(bromoacetamido)benzyl]-5-methoxy-2-methylindole-3
      acetic acid (I) and 4-(bromoacetamido)-N-(2,3-dimethylphenyl)anthranilic acid
      (II), were synthesized on the basis of their respective nonsteroidal anti
      inflammatory drugs (NSAIDs), indomethacin and mefenamic acid [Askonas & Penning
      (1991) Biochemistry 30, 11553-11560]. Compounds I and II are now shown to inhibit
      homogeneous ram seminal vesicle prostaglandin H2 (PGH2) synthase by two
      kinetically distinct complexes. They are competitive inhibitors versus
      arachidonic acid via the formation of high-affinity E.I complexes, and they cause
      time-dependent inactivation of the holoenzyme via low-affinity E.I complexes.
      Compounds I and II, unlike classical NSAIDs, were found to inactivate both the
      cyclooxygenase and peroxidase reactions of the synthase in a parallel manner.
      Inactivation was accompanied by the incorporation of 2 mol of either radiolabeled
      I or II per synthase monomer. The covalent bonds that result were stable to
      boiling in SDS, indicating that I and II offer alternatives to aspirin in
      locating NSAID binding sites. Incubation of aspirin-treated PGH2 synthase with
      radiolabeled I reduced the stoichiometry of incorporation to 1.0, suggesting that
      one of the sites modified corresponds to the cyclooxygenase site. By saturating
      the cyclooxygenase site with mefenamic acid, I and II only abolished the
      peroxidase activity of the enzyme, suggesting that the second site of
      modification corresponds to the peroxidase site. When PGH2 synthase was incubated
      with mefenamic acid and I or II, only the peroxidase activity was inactivated.
      Subsequent removal of all drugs by dialysis gave a preparation of PGH2 synthase
      that could perform the cyclooxygenase reaction, but lacked the ability to cleave
      ethyl hydroperoxide to ethanol and water.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7827040
TI  - Mechanistic studies of aromatic amine dehydrogenase, a tryptophan
      tryptophylquinone enzyme.
AB  - Aromatic amine dehydrogenase (AADH) is the second enzyme known to possess the
      tryptophan tryptophylquinone (TTQ) prosthetic group. Its ability to catalyze the
      oxidative deamination of a wide range of aromatic and aliphatic amines has been
      investigated. Steady-state and transient kinetic studies of the reaction of AADH
      with a series of p-substituted phenylethylamines were performed to determine
      structure-reactivity correlations. The Km values correlated strongly with
      hydrophobic effects. The microscopic rate constant associated with TTQ reduction,
      k3, correlated with electronic substituent effects, particularly field/inductive
      effects, in a manner consistent with the formation of a carbanionic reaction
      intermediate in the reductive half-reaction. Transient kinetic studies were also
      performed with a series of p-substituted benzylamines, which were not substrates
      in the steady-state assay, but which did stoichiometrically reduce TTQ. The k3
      for the reaction with benzylamines also correlated well with electronic effects.
      The rate constant associated with the release of the aldehyde product was also
      determined for the phenylethylamines and appears to be the most rate-limiting
      step in the overall oxidation-reduction reaction. This rate constant correlated
      with hydrophobic amines. This substrate specificity for aliphatic amines is
      opposite of that of methylamine dehydrogenase (MADH), the other known TTQ enzyme.
      On the basis of these studies, a reaction mechanism is proposed for AADH. These
      data are discussed in relation to the results of structure-reactivity correlation
      studies of the reactions catalyzed by MADH and two eukaryotic quinoproteins with
      different quinone prosthetic groups, plasma amine oxidase and lysyl oxidase.

PMID- 7827041
TI  - Transient and equilibrium kinetic studies on yeast 3-phosphoglycerate kinase.
      Evidence that an intermediate containing 1,3-bisphosphoglycerate accumulates in
      the steady state.
AB  - The structure of the key glycolytic enzyme 3-phosphoglycerate kinase (PGK) is
      known in detail, but there is little information on its reaction pathway. We have
      studied its equilibrium and transient kinetics in the direction of 1,3
      bisphosphoglycerate (1,3-bis-P-glycerate) production: ATP + 3-P-glycerate<==>ADP
      + 1,3-bis-P-glycerate. We devised a sensitive method for following this
      production. PGK is mixed with 3-P-glycerate and [gamma-32P]ATP in a rapid flow
      quench apparatus. The reaction mixtures are aged for 4 ms or more and then
      quenched in acid in which any [1-32P]-1,3-P-glycerate decomposes to 3-P-glycerate
      and 32Pi, which is determined specifically. The Pi reflects accurately the 1,3
      bis-P-glycerate in the original reaction mixture, and the kcat obtained is
      identical to that obtained by the conventional linked assay method with
      glyceraldehyde-3-phosphate dehydrogenase. This does not support the postulate of
      a rapid direct transfer of the 1,3-bis-P-glycerate between the kinase and the
      dehydrogenase [Srivastava, D. K., & Bernhard, S. A. (1986) Science 234, 1081
      1086]. We fitted our data to a simple scheme with the formation of binary
      complexes, the interconversion of substrates to products via ternary complexes,
      and the release of products. Because of the high turnover of PGK, the work was
      carried out under cryoenzymic conditions with 40% ethylene glycol in the buffer.
      The glycol decreased kcat from 80 to 8.5 s-1 (pH 7.5, 4 degrees C), but the Km
      for 3-P-glycerate and ATP and the equilibrium constants in the scheme were little
      affected. We carried out two types of experiment.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7827042
TI  - Role of the C-terminal helix in the folding and stability of yeast
      phosphoglycerate kinase.
AB  - In order to determine the role of the C-terminal helix in the folding and
      stability of yeast phosphoglycerate kinase, a mutant deleted of the 12 C-terminal
      residues (PGK delta 404-415) was constructed. This mutant folds in a conformation
      very similar to that of the wild-type protein, but exhibits a very low activity
      (0.1% of that of the wild-type enzyme). The main structural effect of the
      deletion of the C-terminal helix is an increase in flexibility of the whole
      protein and a decrease in stability by about 5 kcal/mol. The structural
      properties of the truncated protein are very similar, at least qualitatively, to
      those in the isolated domains. The accessibility of the thiol group of Cys 97 is
      identical to that in the isolated N-domain. The large solvent effect on the
      tryptophan fluorescence in the native protein at very low concentration of
      denaturant reveals an increase of flexibility of the C-domain, similar to that
      observed on the isolated C-domain. NMR measurements show that the pH dependence
      of His C2H and C4H chemical shifts in the truncated protein perfectly matches
      those of the isolated domains. The addition of the missing peptide provokes a 40
      fold increase in enzyme activity at saturation. A dissociation constant of 80
      microM was determined. This peptide, which displays a random structure in
      solution, folds in a helical structure in the region 405-410 as assessed by
      TRNOESY. All these results show that the C-terminal part of yeast
      phosphoglycerate kinase is not necessary for most of the initial folding steps
      but acts to lock the C-domain on the N-domain, thus ensuring the expression of
      full enzyme activity. Without this sequence, the protein has the sum of the
      properties of the two isolated domains.

PMID- 7827043
TI  - Transferred nuclear Overhauser effect study of the C-terminal helix of yeast
      phosphoglycerate kinase: NMR solution structure of the C-terminal bound peptide.
AB  - Two-dimensional 1H nuclear magnetic resonance spectroscopy is used to determine
      the structure of the C-terminal complementary peptide (404-415) bound to a mutant
      phosphoglycerate kinase (1-403). Conformational changes in the peptide induced by
      the formation of the peptide-protein complex are followed by transferred nuclear
      Overhauser effect spectroscopy. Measurement of transferred NOEs and molecular
      modeling reveal an alpha-helix fold in the 405-409 region. This fold is in good
      agreement with the corresponding helix XIV of the crystallographic structure of
      wild-type PGK (Watson et al., 1982). The role of the alpha-helix from the C
      terminal peptide in the recovery of catalytic activity in the mutant PGK is
      discussed.

PMID- 7827044
TI  - Structural comparison of two major endo-1,4-xylanases from Trichoderma reesei.
AB  - Three-dimensional structures of two major endo-1,4-xylanases, XYNI and XYNII from
      Trichoderma reesei, have been determined by X-ray crystallography. The amino acid
      sequences of both enzymes are highly homologous (identity approximately 50%), and
      both XYNI and XYNII exist as a single domain that contains two mostly
      antiparallel beta-sheets which are packed against each other. The beta-sheet
      structure is twisted, forming a cleft where the active site is situated. Two
      glutamic acids in the cleft, Glu75 and Glu164 in XYNI as well as Glu86 and Glu177
      in XYNII, are most likely involved in catalysis. Inspection of the structures
      reveals that the width of the active site cleft and the number of subsites are
      different in XYNI and XYNII. The active site is narrower in XYNI and probably
      contains only three subsites, whereas the number of subsites in XYNII is most
      likely five. Variations in the surroundings of catalytic residue
      Glu164XYNI/Glu177XYNII are thought to explain the pH optimum differences observed
      in XYNI and XYNII.

PMID- 7827045
TI  - Comparison of the backbone dynamics of a folded and an unfolded SH3 domain
      existing in equilibrium in aqueous buffer.
AB  - Two-dimensional NMR 15N relaxation studies have been used to characterize the
      backbone dynamics and folding transition of the N-terminal SH3 domain of the
      protein drk (drkN SH3). The isolated drkN SH3 domain exists in equilibrium
      between a folded and an unfolded state in aqueous buffer and near neutral pH
      [Zhang et al. (1994) J. Biomol. NMR 4, 845]. The backbone dynamics of both the
      folded and unfolded states in this exchanging system have been determined and the
      rates of the folding transition estimated at 14 degrees C. For 12 residues, the
      values of the spectral density functions of the backbone amide bond vectors at a
      number of frequencies have been established. Results show that while the unfolded
      state has considerably greater dynamic behavior, the overall motional properties
      are consistent with it having a reasonably compact structure in solution. In
      contrast to the folded state, considerable variations are seen in the values of
      the spectral densities of the unfolded state as a function of residue number;
      these variations do not appear to be strongly correlated with structural elements
      in the folded state. The mean value of the exchange rate associated with the
      folding transition was determined to be 0.89 s-1, similar to previous
      measurements of the rate of formation of beta-structure.

PMID- 7827046
TI  - Optical studies of a bacterial photoreceptor protein, photoactive yellow protein,
      in single crystals.
AB  - Photoactive yellow protein (PYP), isolated from Ectothiorhodospira halophila, is
      a water soluble, 14 kDa photoreceptor protein with a fully reversible photocycle
      resembling that of sensory rhodopsin II. We have established the presence of
      photoactivity in PYP crystals and defined the relaxation kinetics of
      spectroscopically distinguishable species in quantitative terms. The PYP crystal
      has a bright yellow color and displays pronounced anisotropic absorption
      properties. Linear dichroism measurements show that the transition moment of the
      PYP chromophore makes an angle of 73 degrees (or 107 degrees) with respect to the
      six-fold crystallographic symmetry axis. The crystal absorbance can be bleached
      reversibly as indicated by absorption changes. A bleached photostationary state
      in the crystal can be established via CW laser illumination, and the extent of
      crystal bleaching is found to be clearly dependent on excitation laser
      wavelength, intensity and illumination time. These results provide the
      information for designing time-resolved crystallography experiments in which a
      minimum perturbation is applied to the PYP crystals. Global exponential fitting
      shows that the relaxation from the photostationary state in the crystal is
      biphasic at -4 degrees C; a slower component of 1.4 +/- 0.2 s-1 accounts for 60%
      of the absorbance change and a faster component of 5.2 +/- 0.9 s-1 for the other
      40%. As a control, we found that the kinetics for the same relaxation in solution
      are well described by one exponential and agree quantitatively with previous
      studies. The two rate constants observed in the crystal show similar temperature
      dependences, with activation energies for the slow and fast components of 11.7 +/
      1.2 and 5.5 +/- 2.3 kcal/mol, respectively. However, the amplitudes associated
      with the two exponents show different and opposite temperature dependence. Our
      results show that the solution kinetic model is not directly applicable to
      crystals. A kinetic model consistent with the optical data is important to
      extract the underlying structural intermediates from the time-resolved X-ray
      diffraction data obtained in parallel with the optical data described here. We
      propose an alternative model for the photocycle in the crystal which contains an
      additional bleached intermediate in parallel with the last long-lived
      intermediate in the solution model.

PMID- 7827047
TI  - DNA polymerase epsilon interacts with proliferating cell nuclear antigen in
      primer recognition and elongation.
AB  - Kinetic analysis of DNA polymerase epsilon in its interaction with the
      homopolymeric template-primer poly(dA)/oligo(dT) and a singly-primed synthetic
      oligonucleotide of defined sequence indicated that primer utilization is
      inhibited by single-stranded DNA. Long single-stranded DNA regions appear to
      sequester DNA polymerase epsilon via nonproductive binding, thus reducing its
      catalytic efficiency. Proliferating cell nuclear antigen can reduce this
      nonproductive effect by increasing the rate of primer binding by DNA polymerase
      epsilon. Once the complex between DNA polymerase epsilon and the primer is
      formed, proliferating cell nuclear antigen can increase the rate of nucleotide
      incorporation. The results suggested a dual role of proliferating cell nuclear
      antigen in stimulating the activity of DNA polymerase epsilon, namely, first to
      facilitate primer binding and second to stimulate the synthetic activity itself.
      A model for the interaction between these two proteins in DNA synthesis is
      discussed.

PMID- 7827048
TI  - Higher order folding and domain analysis of the ribozyme from Bacillus subtilis
      ribonuclease P.
AB  - Folding of the ribozyme from Bacillus subtilis ribonuclease P (denoted P RNA) has
      been examined by Fe(II)-EDTA protection and bimolecular association. Fe(II)-EDTA
      results show that, in the presence of Mg2+, P RNA is folded into a core structure
      which includes most of the phylogenetically conserved nucleotides. Folding is
      cooperative and is complete at 5-6 mM Mg2+ with the [Mg2+]1/2 at 2-3 mM. The Hill
      constant indicates that this folding transition requires binding of at least
      three additional Mg2+ ions. Two RNA molecules consisting of nucleotides 62-239
      [p(62-239)] and 240-401 + 1-61 [p(240-61)] of the B. subtilis P RNA have been
      constructed. These RNAs can in principle form the catalytically active structure
      primarily, if not solely, through tertiary interactions. Although either molecule
      by itself is inactive, the bimolecular complex is as active as the circularly
      permuted P RNAs from which it is derived. The binding constant of the complex can
      be as low as 0.1 microM and is strongly dependent on Mg2+ and K+ concentrations.
      Association of these molecules also induces a Mg2+ dependent cleavage at
      nucleotide 103 in p(62-239). p(62-239) gives a Fe(II)-EDTA protection pattern
      very similar to the wild-type P RNA at identical Mg2+ concentrations. However,
      Fe(II)-EDTA protection in p(240-61) is completely lost, even though it contains
      many nucleotides that are conserved among all P RNAs. These results suggest that,
      like other RNAs, P RNA contains domains that can fold in the absence of the rest
      of the molecule. The implications of these results are discussed in the context
      of the P RNA structure and catalysis.

PMID- 7827049
TI  - Reduction of chromium(VI) by ascorbate leads to chromium-DNA binding and DNA
      strand breaks in vitro.
AB  - Chromium(VI) is a known human carcinogen which requires intracellular reduction
      for activation. Ascorbate (vitamin C) has been reported to function as a major
      reductant of Cr(VI) in animals and cell culture systems. The reaction of Cr(VI)
      with varying concentrations of ascorbate was studied under physiological
      conditions in vitro in order to determine the types of reactive intermediates
      produced and to evaluate the reactivity of these intermediates with DNA.
      Reactions of 1.8 mM Cr(VI) with 0-18 mM ascorbate at pH 7.0 in N-(2
      hydroxyethyl)piperazine-N'-2-ethanesulfonic acid (HEPES; 0.10 M) and
      tris(hydroxymethyl)aminomethane hydrochloride (Tris.HCl; 0.050 M) buffers were
      studied by electron paramagnetic resonance and UV/visible spectroscopy. Cr(V) and
      carbon-based free radical adducts of 5,5-dimethyl-1-pyrroline 1-oxide (DMPO) were
      observed at 0.5 to 1 and 1 to 1 reactions of ascorbate to Cr(VI). Levels of Cr(V)
      were higher for reactions in HEPES buffer, and levels of carbon-based radicals
      were higher in Tris.HCl buffer. Levels of Cr(IV) and Cr(III) increased with
      increasing concentration of ascorbate in both buffers. Reaction of Cr(VI) with
      varying ascorbate in the presence of calf thymus DNA or pBR322 DNA resulted in Cr
      DNA adducts and plasmid relaxation, respectively. Maximum binding of Cr to DNA
      was observed for the 1:1 reaction ratio of Cr(VI) with ascorbate in both HEPES
      and Tris.HCl buffers, but total Cr bound to DNA was 8-fold lower in Tris.HCl than
      HEPES buffer. Preincubation of Cr(VI) with ascorbate before reaction with DNA
      decreased Cr-DNA binding to background levels. Preincubation of Cr(III) with
      ascorbate resulted in only low Cr-DNA binding. Levels of Cr-DNA binding were
      higher with single-stranded vs double-stranded DNA. Reactions with 14C-labeled
      ascorbate produced no cross-linking of ascorbate to DNA. Maximum plasmid
      relaxation was observed for the 1:1 ascorbate to Cr(VI) ratio in both buffers;
      however, single-strand breaks were 2-fold higher in Tris.HCl than HEPES buffer.
      Reactions with plasmid in the presence of DMPO quenched formation of single
      strand breaks. Interpretation of these results in light of the spectroscopic
      studies suggested that Cr(V) and carbon-based radicals were responsible for Cr
      DNA adducts and DNA single-strand breaks, respectively.

PMID- 7827050
TI  - Structural domains of DNA mesojunctions.
AB  - Holliday junctions are central intermediates in the process of genetic
      recombination. These DNA molecules contain four double helices that flank a
      central branch point, so that each of the four strands that constitute the
      junction is associated with two different helices. Previously, we have shown that
      such branched junctions are a special subset of the class of DNA molecules
      containing multiple strands, in which each strand is associated with two double
      helices [Du, S. M., Zhang, S., & Seeman, N. C. (1992) Biochemistry 31, 10955
      10963]. Conventional branched molecules, such as the Holliday junction, contain
      helices whose axes can all be drawn to radiate from a central point. The other
      molecules of the class contain helices whose axes are circumferential about the
      central point. If all of the helices are circumferential, the molecule is called
      an antijunction; if the molecule contains a mixture of radial and circumferential
      helices, it is called a mesojunction. The properties of the molecule are a
      function of the even or odd nature of the number of helical half-turns in the
      circumferential helices. Previously, a four-strand antijunction and three-strand
      and four-strand mesojunctions containing three half-turns (16 nucleotide pairs)
      per helix were constructed and characterized. Here, we have attempted to
      construct the analogous molecules containing two half-turns (10 nucleotide pairs)
      in each helix. The three-strand mesojunction and the four-strand antijunction are
      not stable under conditions suitable for analysis. We have characterized the two
      four-strand mesojunctions that are stable by Ferguson analysis, thermal
      denaturation, and Fe(II)EDTA2- autofootprinting. In addition, we have
      characterized a four-strand mesojunction containing 14 nucleotide pairs in its
      circumferential helices and have shown that its favored conformer is different
      from that of a closely related molecule containing 16 nucleotide pairs in its
      circumferential helices.

PMID- 7827051
TI  - Mechanism of Ca-ATPase inhibition by melittin in skeletal sarcoplasmic reticulum.
AB  - We have previously shown that the basic, amphipathic peptide melittin inhibits
      the Ca-ATPase of the sarcoplasmic reticulum membrane by inducing large-scale
      aggregation of the enzyme via electrostatic cross-linking. To better understand
      the physical mechanism by which melittin-induced Ca-ATPase aggregation inhibits
      the enzyme, we have performed time-resolved phosphorescence anisotropy (TPA) and
      steady-state fluorescence experiments in combination with enzyme kinetic assays,
      utilizing (1) native and charge-modified melittin in order to characterize the
      peptide charge dependence of the melittin-SR interaction, and (2) various calcium
      levels in order to define the effect of melittin on the enzyme's E1 and E2
      conformational equilibrium. TPA results showed that decreasing melittin's
      positive charge dramatically decreases the ability of the peptide to aggregate
      the enzyme, which correlates with a reduced potency of the modified peptide to
      inhibit enzymatic activity. Steady-state fluorescence of fluorescein
      isothiocyanate-labeled Ca-ATPase showed that melittin reduces Ca-ATPase affinity
      for calcium by shifting the enzyme's E1-E2 conformational equilibrium toward E2,
      but increasing calcium progressively reverses this shift. Kinetic experiments
      showed that melittin does not prevent ATP-dependent enzyme phosphorylation, but
      it completely inhibits Pi-dependent EP formation and substantially slows Pi
      release during steady-state cycling. We conclude that melittin-induced
      aggregation of the Ca-ATPase depends on the electrostatic interaction of the
      peptide with cytoplasmic Ca(2+)-dependent sites on the enzyme, and that enforced
      Ca-ATPase protein-protein interactions inhibit the conformational transitions
      that facilitate phosphoenzyme hydrolysis.

PMID- 7827052
TI  - Sulfate-activating enzymes in normal and brachymorphic mice: evidence for a
      channeling defect.
AB  - The severe reduction in the amount of 3'-phosphoadenosine 5'-phosphosulfate
      (PAPS) in cartilage from homozygous brachymorphic mice results from a decrease in
      the activities of both ATP sulfurylase (50%) and adenosine 5'-phosphosulfate
      (APS) kinase (14% of normal). In order to better understand the etiology of this
      double enzyme defect, a dual approach to elucidating the nature of the enzyme
      complex as well as its mechanistic properties was undertaken. Antibody reagents
      that react with both activities provide evidence for a single, bifunctional
      protein in both normal and mutant cartilage. Quantitative Western blot analysis
      indicates that a normal amount of a dysfunctional protein is produced in mutant
      cartilage. Kinetic studies show that the Vmax for mutant kinase is significantly
      reduced and that mutant sulfurylase and kinase appear to have lower KmAPS values
      than normal. Interestingly, the mutation appears to disrupt the channeling
      mechanism that has recently been demonstrated for this pathway [Lyle et al.
      (1994) Biochemistry 33, 6822-6827]. APS kinase from normal mouse cartilage
      utilizes APS supplied by ATP sulfurylase much more efficiently than APS which is
      added exogenously; i.e., channeling efficiency is > 90%. In contrast, the mutant
      enzymes exhibit only 54% channeling efficiency. Lastly, isotope dilution and
      enrichment experiments show directly that the APS binding sites of the mutant
      enzymes are more accessible to free APS than are those of the normal enzymes.
      These data suggest that the mutation primarily affects the catalytic properties
      of the PAPS activation system by altering the function of the novel coupling
      mechanism between the two activities, causing a decrease in the ability to
      channel APS and produce PAPS efficiently.

PMID- 7827053
TI  - Transmembrane domain inversion blocks ER release and insulin receptor signaling.
AB  - Activation of the insulin receptor, like other tyrosine kinase receptors, appears
      to require dimerization. We have shown previously that, even in the absence of
      insulin, full receptor activation can be induced by changes in the receptor
      transmembrane domain (TMD), suggesting that TMD dimerization is sufficient for
      receptor activation. To further understand the importance of the TMD in insulin
      receptor activation, we have inverted the entire TMD sequence including flanking
      basic amino acids, residue-for-residue. This mutation was predicted to alter the
      ability of a TMD alpha-helix to form homodimers and higher level aggregates.
      Despite apparently normal protein folding on either side of the membrane, this
      mutation caused ER retention and, for those receptors that reached the cell
      surface, blockade of insulin-stimulated kinase signal transmission. However, the
      signaling blockade could be overcome by proteolytic activation with trypsin. In
      contrast, shifting only the basic cytoplasmic residues to the opposite side of
      the TMD or mutation to neutral residues had no detectable effect on assembly,
      biosynthesis, topology, or signaling. These findings extend our previous
      observations to suggest that TMD interactions within the membrane are not only
      sufficient for receptor activation, but may be required. TMD interactions also
      appear to be necessary for oligomeric assembly and biosynthetic maturation of the
      insulin receptor.

PMID- 7827054
TI  - Evaluation of conformational and binding characteristics of various natriuretic
      peptides and related analogs.
AB  - The conformational properties of atrial natriuretic factor (ANF), brain
      natriuretic peptide (BNP), and various analogs and homologs were studied by
      circular dichroism (CD) spectroscopy in solvent mixtures inducing secondary
      structures. The CD spectra obtained for rat ANF(99-126), porcine BNP32, and their
      related analogs indicated that these peptides exhibited mainly a random-coil
      conformation in pure water. However, the addition of increasing concentrations of
      1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) gave rise for all peptides to a more
      ordered secondary structure. The analysis of the far-ultraviolet CD spectra
      suggested that the peptides exist under two conformational states, beta-turn and
      beta-sheet, in the presence of 20-60% HFIP/water solutions. Moreover, the
      characterizations of rANF(99-126) and the analog pBNP1, which combines the cyclic
      core of bBNP32 with the carboxy- and amino-terminal segments of rANF-(99-126),
      have been carried out by Fourier transform infrared spectroscopy (FTIR) in 40%
      HFIP/D2O. The FTIR results indicated that these peptides exist predominantly
      under a beta-turn and beta-sheet mixed conformation. In addition, the amount of
      organized secondary structure obtained for human BNP32, bovine aldosterone
      secretion inhibitory factor, also known as ASIF(69-103) and beta-rANF(92-126), in
      the presence of a 40% HFIP/phosphate buffer mixture, was similar to that of
      porcine BNP32, whereas rat BNP32 was found to be more structured. In the same
      solvent mixture, the CD spectra of Met(O)110-human ANF(99-126) and chicken ANF(99
      126) indicated that these peptides possess conformational features different to
      those of rANF(99-126) and hANF(99-126). Porcine CNP22, C-type natriuretic
      peptide, and the fragment C-ANF exhibited undefined secondary structure in the
      presence of 40% HFIP/phosphate buffer. These results suggest that the amino acid
      residues, not common to the various natriuretic peptides, would be involved in
      the stabilization of either beta-turn and/or beta-sheet conformations. Moreover,
      these secondary structures appear as particularly important for the recognition
      of the ANF-R1A receptor subtype found in bovine adrenal cortex.

PMID- 7827055
TI  - Photooxidation of Trp-191 in cytochrome c peroxidase by ruthenium-cytochrome c
      derivatives.
AB  - A novel photoinduced electron-transfer reaction is reported in complexes between
      resting ferric state cytochrome c peroxidase (CcP) and several horse cytochrome c
      derivatives labeled at single lysine amino groups with
      [bis(bipyridine)](dicarboxybipyridine)ruthenium(II) (Ru-CC). Photoexcitation of
      Ru(II) in the 1:1 Ru-27-CC:CcP complex results in formation of a metal-to-ligand
      charge-transfer state, Ru(II*), which is a strong reducing agent and rapidly
      transfers an electron to the CC heme Fe(III) with rate constant k1 = 2.3 x 10(7)
      s-1. The resulting Ru(III) is a strong oxidizing agent with a redox potential of
      1.3 V, and it oxidizes the indole ring of Trp-191 with rate constant k3 = 7 x
      10(6) s-1. The cycle is completed by electron transfer from Fe(II) in CC to the
      Trp-191 radical in CcP with rate constant k4 = 6.1 x 10(4) s-1. The Ru group is
      located close to the interaction domain in the Ru-27-CC:CcP complex, allowing
      rapid electron transfer with both the heme in CC and Trp-191 in CcP. The electron
      transfer reaction was not observed in CcP compound I, where Trp-191 is already
      oxidized to the radical, or in the W191F mutant, where the indole group is
      replaced with a phenyl group. The electron-transfer reaction was observed in CcP
      mutants modified at residues in the heme crevice, R48K, R48L, H52L, M230I, and
      M231I, but not in D235N which destabilizes the radical on Trp-191. Increasing the
      ionic strength results in an increase in the equilibrium dissociation constant K
      of the Ru-27-CC:CcP complex and an increase in the rate constant k5 for
      dissociation of the transient intermediate containing Fe(II) CC and the radical
      form of CcP. Both K and k5 were also increased significantly by the mutations
      D34N, E290N, and A193F involving residues located in the interaction domain of
      the crystalline complex between yeast CC and CcP [Pelletier & Kraut (1992)
      Science 258, 1748-1755]. This new method allows the study of the electron
      transfer reaction between CC and the radical on Trp-191 in the complete absence
      of hydrogen peroxide, and it opens the possibility of measurements at low
      temperatures in frozen glasses or in crystals.

PMID- 7827056
TI  - Stabilization of helical domains in short peptides using hydrophobic
      interactions.
AB  - The contribution of hydrophobic interactions in the stabilization of helical
      structure was compared for a series of short peptides that incorporated two
      epsilon-(3,5-dinitrobenzoyl)Lys residues at various positions. Results showed
      that in aqueous/organic mixtures, methanol induced helical stability over a wider
      range and at higher concentration than trifluoroethanol (TFE); a similar degree
      of stability was seen in low mole fraction mixtures of TFE in water. Solvent
      mixture titrations in TFE/water demonstrated that helical stability was highest
      for the peptide having a pair of modified residues spaced by three other
      residues. Solvent mixture titrations in TFE/water appear to be useful in
      indicating the degree of hydrophobic stabilization.

PMID- 7827057
TI  - Interconversion of the CD and EF sites in oncomodulin. Influence on the Eu3+ 7F0-
      >5D0 excitation spectrum.
AB  - The appearance of the parvalbumin Eu3+ 7F0-->5D0 spectrum is markedly pH
      dependent, the result of a hitherto unidentified deprotonation event in the CD
      ion-binding domain [Trevino, C.L., et al. (1991) J. Biol. Chem. 265, 9694-9700].
      We are studying this phenomenon in the mammalian placental parvalbumin called
      oncomodulin. As in other parvalbumins, the liganding residues in the CD and EF
      sites of oncomodulin differ at the +z and -x coordination positions: serine and
      aspartate, respectively, in the CD site; aspartate and glycine in the EF site. We
      have prepared a series of oncomodulin variants in which the +z and/or -x
      residue(s) from one site have been replaced by the corresponding residue(s) from
      the other. We herein characterize the resulting proteins by Eu3+ luminescence
      spectroscopy. Simultaneous replacement of serine-55 by aspartate and aspartate-59
      by glycine affords the CD site with a coordination sphere superficially
      equivalent to that of the EF site. As observed previously for the S55D mutation
      [Henzl, M. T., et al. (1992) FEBS Lett. 314, 130-134], the Eu3+ 7F0-->5D0
      spectrum of the 55/59 variant is pH independent. Interestingly, replacement of
      aspartate-94 by serine at the +z position of the EF site of 55/59 imparts pH
      dependent behavior to the EF site. The identical mutation in the wild-type
      background likewise imparts pH dependence to the EF site, affording a protein in
      which both sites display broad signals near 578.2 nm at pH 8. Significantly, a
      variant in which threonine replaces serine-55 retains the pH dependent
      spectroscopic signature. These results indicate that the presence of a hydroxyl
      group at the +z position is sufficient to confer pH dependence on the 7F0-->5D0
      spectrum of a parvalbumin EF-hand domain. Importantly, the data also suggest that
      the component peaks of the low-pH doublet are not site-specific signals, as
      previously believed. Rather, they probably represent differences in coordination
      environment arising from differential hydration or conformational heterogeneity.
      In wild-type oncomodulin, the CD site signal dominates the low-pH spectrum. Since
      this dominance persists even when serine-55 and aspartate-59 are replaced by the
      corresponding EF site residues, it appears that the context of the CD binding
      site, as dictated by the global polypeptide fold, exerts a major influence on the
      metal ion-binding properties of the site.

PMID- 7827058
TI  - Design of a membrane protein for site-specific proteolysis: properties of
      engineered factor Xa protease sites in the lactose permease of Escherichia coli.
AB  - Lactose permease is a polytopic membrane transport protein with 12 hydrophobic
      transmembrane domains connected by hydrophilic loops on the cytoplasmic and
      periplasmic sides of the membrane. By the use of an active permease mutant devoid
      of Cys residues (C-less permease), single recognition sites (Ile-Glu-Gly-Arg) for
      the protease factor Xa (fXa) were engineered into hydrophilic loops 7, 8, and 10
      in the C-terminal half of the protein. Mutants carrying single sites inserted at
      position 255, 259 (loop 7), 283, 286 (loop 8), or 341 (loop 10) exhibit
      significant lactose accumulation (30-70% of C-less permease) and normal levels of
      expression in the membrane. However, despite solubilization in dodecyl beta-D
      maltoside, none of the mutant permeases is proteolyzed by fXa to a significant
      extent. Insertion of two recognition sites in tandem at position 255 results in
      partial cleavage, and remarkably, introduction of three sites in tandem leads to
      complete proteolysis by fXa. Importantly, mutants with two or three fXa sites at
      position 255 accumulate lactose to high levels (70% of C-less) and are present in
      the membrane in amounts comparable to that of C-less permease. The results
      indicate that hydrophilic loops 7, 8, and 10 are buried in the tertiary structure
      of the permease where they are inaccessible to protease. Insertion of tandem
      sites probably facilitates proteolysis by causing loops to become more accessible
      to the aqueous phase and by increasing the local concentration of protease
      recognition sites. The approach should be applicable to other polytopic membrane
      proteins.

PMID- 7827059
TI  - Specific DNA recognition by EcoRV restriction endonuclease induced by calcium
      ions.
AB  - In the presence of Mg2+, the EcoRV restriction endonuclease cleaves DNA
      specifically at its recognition sequence, but in the absence of divalent metal
      ions, it binds DNA without any specificity: gel-shift experiments had revealed
      multiple EcoRV-DNA complexes, due to the binding of one, two, three, or more
      molecules of protein per molecule of DNA, with the same equilibrium constant for
      each association. In this study, the binding of EcoRV to DNA was measured by gel
      shift in the presence of Ca2+, an ion that perturbs the Mg(2+)-dependent activity
      of EcoRV but that fails to support DNA cleavage. With Ca2+, and at a lower
      concentration of EcoRV protein than that required for binding in the absence of
      divalent metal ions, a single complex was observed with DNA containing the EcoRV
      recognition site. This complex was not formed with DNA that had been methylated
      at the EcoRV site nor with an isogenic DNA lacking the EcoRV recognition site.
      The single complex thus is due to the specific binding of EcoRV to its
      recognition site on the DNA. From gel shifts with a permuted set of DNA
      fragments, the degree of DNA bending by EcoRV at its recognition site was
      estimated to be 53 degrees +/- 4 degrees. This angle is similar to that seen in
      the crystal structure of the cognate DNA-protein complex. Calcium ions thus
      appear to mimic the role of Mg2+ in generating a specific protein-metal-DNA
      complex, but in contrast to Mg2+, Ca2+ gives a stable ternary complex in which
      the DNA-bound nuclease cannot cleave the DNA.

PMID- 7827060
TI  - Role of entropic interactions in viral capsids: single amino acid substitutions
      in P22 bacteriophage coat protein resulting in loss of capsid stability.
AB  - Bacteriophage P22 is a double-stranded DNA containing phage. Its morphogenetic
      pathway requires the formation of a precursor procapsid that subsequently matures
      to the capsid. The stability of bacteriophage P22 coat protein in both monomeric
      and polymeric forms under hydrostatic pressure has been examined previously
      [Prevelige, P. E., King, J., & Silva, J. L. (1994) Biophys. J. 66, 1631-1641].
      The monomeric protein is very unstable to pressure and undergoes denaturation at
      pressures below 1.5 kbar, whereas the procapsid shell is very stable to applied
      pressure and does not dissociate with pressure to 2.5 kbar. However, under
      applied pressure the procapsid shells are cold labile, suggesting they are
      entropically stabilized. We have analyzed the pressure stability of mutant
      procapsid shells having either of two single amino acid substitutions in the coat
      protein (G232D and W48Q) using light-scattering and fluorescence emission
      methods. While the wild-type shells were stable under 2.2 kbar of pressure at
      room temperature (22 degrees C), the G232D mutant shells showed time-dependent
      dissociation under these conditions. Decreasing the temperature to 1 degree C
      dramatically accelerated the dissociation of G232D mutant under applied pressure.
      On the other hand, the W48Q mutant shells could be dissociated easily by pressure
      at room temperature and displayed little dependence on temperature, suggesting a
      smaller entropic contribution to the stability of this mutant. The unpolymerized
      mutant subunits displayed a pressure stability similar to that of the wild
      type.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7827061
TI  - Facilitated intramolecular electron transfer in the Escherichia coli bo-type
      ubiquinol oxidase requires chloride.
AB  - Previous flow-flash measurements using the bo-type ubiquinol oxidase of
      Escherichia coli have revealed that facilitated heme B-heme O intramolecular
      electron transfer initiated upon reaction of the fully-reduced enzyme with
      dioxygen proceeds with a rate constant higher than 5 x 10(4) s-1 at pH 7.4 and 20
      degrees C. Depletion of chloride anions from the enzyme by HPLC performed in the
      present study considerably decreased the rate constant to approximately 700 s-1,
      but the reaction of either dioxygen or carbon monoxide at the binuclear center
      was not affected at all kinetically. These results strongly suggest that Cl- is
      essential in maintaining a subtle molecular structure around the heme B and heme
      O that enables facilitated intramolecular electron transfer. Furthermore, a
      series of absorption spectra of the enzyme collected on time scales from
      microseconds to milliseconds during its single turnover indicate that as heme
      heme intramolecular electron transfer is retarded by depletion of Cl-, an
      alternative electron transfer pathway is invoked. We discuss a possible role of
      novel bound Cl- in electron transfer from bound quinol to the binuclear center to
      accomplish dioxygen reduction.

PMID- 7827062
TI  - Phosphorescence reveals a continued slow annealing of the protein core following
      reactivation of Escherichia coli alkaline phosphatase.
AB  - When Escherichia coli alkaline phosphatase (AP) is refolded in vitro after
      extensive denaturation in 6.2 M guanidine hydrochloride, the enzymatic activity
      reaches its asymptotic value in 1 h at 24 degrees C. In contrast, the structural
      rigidity of the hydrophobic core of the protein, monitored by the recovery of the
      tryptophan phosphorescence lifetime, returns to its characteristic native-like
      value over several days. Moreover, the protein lability, measured by the rate of
      inactivation in 4.5 M guanidine hydrochloride, also changes on a time scale much
      longer than the recovery of activity. These results clearly demonstrate that
      while the return of enzymatic activity, the traditional measure of the attainment
      of the native state, indicates that AP has refolded to its final, active
      conformation, the phosphorescence data indicate otherwise. In the context of the
      rugged energy landscape model [Frauenfelder, H., et al. (1991) Science 254, 1598
      1603], the slow annealing of the hydrophobic core is consistent with the presence
      of high-energy barriers that separate fully active intermediates along the
      folding pathway. The data suggest that the core of the protein undergoes
      continued structural rearrangements affecting the rigidity of the protein
      environment surrounding the emitting tryptophan and the protein lability long
      after the return of enzyme activity.

PMID- 7827063
TI  - Observation of the hydration-dependent conformation of the (dG)20.(dG)20(dC)20
      oligonucleotide triplex using FTIR spectroscopy.
AB  - The triple-helical oligonucleotide (dG)20.(dG)20(dC)20 was investigated using
      FTIR spectroscopy. Mid-infrared spectra were collected at nine relative
      humidities (RH) between 0% and 98%. The highest humidity spectrum agrees with the
      solution spectrum of a polynucleotide (dG)n.(dG)n(dC)n triplex [Quali, M.,
      Letellier, R., Sun, J. S., Akhebat, A., Adnet, F., Liquier, J., & Taillandier, E.
      (1993) J. Am. Chem. Soc. 115, 4264-4270]. A dramatic transition in the
      vibrational state of the molecule has been observed between 88% and 92% RH.
      Theoretical predictions concerning the effects of hydration on a (dG).(dG)-(dC)
      oligonucleotide triplex [Laughton, C. A., & Neidle, S. (1992) Nucleic Acids Res.
      20, 6535-6541; Mohan, V., Smith, P.E., & Pettitt, M.B. (1993) J. Am. Chem. Soc.
      115, 9297-9298] have been considered and compared to our results. The infrared
      marker bands for the conformation of the glycosidic bond are absent below 92% RH,
      although dramatic hydration-dependent vibrational changes have been observed in
      the spectral regime traditionally associated with the glycosidic linkages. The
      effect of water in the Watson-Hoogsteen groove upon the vibrational state of the
      triplex has been observed for the first time. Hydration-induced changes in
      vibrational state have also been observed in the base residues, the
      phosphodiester backbone, and the furanose rings of the oligonucleotide sample.

PMID- 7827064
TI  - Effect of point mutations on the kinetics and the inhibition of human
      immunodeficiency virus type 1 protease: relationship to drug resistance.
AB  - Mutations of human immunodeficiency virus type 1 (HIV-1) protease at four
      positions, Val82, Asp30, Gly48, and Lys45 were analyzed for the resulting effects
      on kinetics and inhibition. In these mutants, Val82 was substituted separately by
      Asn, Glu, Ala, Ser, Asp, and Gln; Asp30 was individually substituted by Phe or
      Trp; Gly48 by His, Asp, and Tyr, respectively; and Lys45 by Glu. By examination
      of the inhibition of a single inhibitor, the differences in Ki values between the
      native and mutant enzymes can range from very large to insignificant even for the
      mutants with substitutions at the same position. By examination of a single
      mutant enzyme, the same broad range of Ki changes was observed for a group of
      inhibitors: Thus, how much the inhibition changes from the wild-type enzyme to a
      mutant is dependent on both the mutation and the inhibitor. The examination of Ki
      changes of inhibitors with closely related structures binding to Val82 mutants
      also reveals that the change of inhibition involves subsites in which Val82 is
      not in direct contact, indicating a considerable flexibility of the conformation
      of HIV protease. For the catalytic activities of the mutants, the kcat and Km
      values of many Val82 mutants and a Lys45 mutant are comparable to the native
      enzyme. Surprisingly, Gly48 mutations produce enzymes with catalytic efficiency
      superior to that of the wild-type enzyme by as much as 10-fold. Modeling of the
      structure of the mutants suggests that the high catalytic efficiency of some
      substrates is related to an increase of rigidity of the flap region of the
      mutants. The examination of the relative changes of inhibition and catalysis of
      mutants suggests that some of the Val82 and Gly48 mutants are potential
      resistance mutants. However, the resistance is specific with respect to
      individual inhibitors.

PMID- 7827065
TI  - Pre-steady-state transition-state analysis of the hydrolytic reaction catalyzed
      by purine nucleoside phosphorylase.
AB  - The slow hydrolytic reaction catalyzed by calf spleen purine nucleoside
      phosphorylase [Kline, P. C., & Schramm, V. L. (1992) Biochemistry 31, 5964-5973]
      has been investigated using pre-steady-state kinetic isotope effects and
      solvolysis studies. The stoichiometric reaction between enzyme and inosine forms
      1 mol of free ribose per trimer of purine nucleoside phosphorylase and a tightly
      bound complex of enzyme and hypoxanthine. The experimental kinetic isotope
      effects from [1'-3H]-, [2'-3H]-, [4'-3H]-, [5'-3H]-, [1'-14C]-, and [9
      15N]inosine are 1.151 +/- 0.004, 1.145 +/- 0.003, 1.006 +/- 0.004, 1.028 +/-
      0.005, 1.045 +/- 0.005, and 1.000 +/- 0.005, respectively, for the pre-steady
      state conditions. Substrate trapping experiments demonstrated that there is no
      detectable forward commitment to catalysis for inosine hydrolysis. In contrast,
      bound inosine is 2.1 times more likely to form product than to dissociate when
      the enzyme-inosine complex is exposed to saturating PO4. The lack of an observed
      9-15N isotope effect is consistent with an internal equilibrium between enzyme
      inosine and the enzyme-hypoxanthine-ribose complex in which N9 of hypoxanthine is
      protonated. The equilibrium occurs as a consequence of slow product release and
      tightly bound hypoxanthine (Kd = 1.3 x 10(-12) M). This internal equilibrium has
      a minimal effect on the intrinsic kinetic isotope effects from ribose since
      equilibrium isotope effects for conversion of inosine to ribose are near unity.
      When the single-turnover hydrolytic reaction was accomplished in 20% methanol,
      approximately 85% of the product sugar was 1-methylribose. Under these
      conditions, the anion-binding pocket fills with solvent which competes for the
      oxocarbenium ion of inosine formed at the transition state. In the presence of
      arsenate, no methanolysis of inosine occurs [Kline, P. C., & Schramm, V. L.
      (1993) Biochemistry 32, 13212-13219]. The results define a transition state with
      oxocarbenium ion character and weak participation of the attacking solvent
      nucleophile. Electrostatic potential surfaces of the transition states indicate
      that arsenate anion is more effective in neutralizing the oxocarbenium ion than
      is H2O.

PMID- 7827066
TI  - Warfarin causes the degradation of protein C precursor in the endoplasmic
      reticulum.
AB  - Warfarin, an antagonist of vitamin K, is known to disrupt the microsomal vitamin
      K cycle, which results in a decrease in the plasma level of protein C, an
      anticoagulant factor, as well as some other vitamin K-dependent coagulation
      factors. Here, we examined the effect of warfarin on the secretion of recombinant
      protein C expressed in human kidney 293 or BHK cells. In transient expression,
      warfarin caused a 2-4-fold decrease in the quantity of protein C secreted,
      compared to findings with vitamin K-treated cells. Pulse-chase experiments using
      stable cells showed that, although recombinant protein C was secreted in the
      presence of vitamin K, the decrease in the total amount of radioactivity in the
      warfarin-treated cells suggested intracellular degradation. This degradation
      depended on the concentration of warfarin and was not inhibited by an endoplasmic
      reticulum (ER)-Golgi transport inhibitor (brefeldin A) or by lysosomotropic
      inhibitors (chloroquine and NH4Cl). Thus, protein C synthesized in the presence
      of warfarin is probably selectively degraded, and this degradation occurs in a
      pre-Golgi, nonlysosomal compartment. Among the protease inhibitors tested, N
      alpha-acetyl-Leu-Leu-methioninal and N-alpha-acetyl-Leu-Leu-norleucinal blocked
      the degradation of protein C precursor synthesized in the presence of warfarin,
      and the precursor accumulated intracellularly, in a dose-dependent manner. Both
      inhibitors, however, did not disturb the secretion of protein C precursor in the
      vitamin K-treated cells. Thus, a cysteine protease(s) appeared to be responsible
      for the degradation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7827067
TI  - Factor IXa inhibition by protease nexin-2/amyloid beta-protein precursor on
      phospholipid vesicles and cell membranes.
AB  - Protease nexin-2/amyloid beta-protein precursor (PN-2/A beta PP) is a Kunitz-type
      protease inhibitor which has been shown to be a tight-binding inhibitor of
      enzymes, factors XIa and IXa (FIXa), suggesting a role for this protein in
      hemostasis. Since coagulant reactions are modulated on biologic surfaces, we
      investigated how 25:75 (mol/mol) phosphatidylserine/phosphatidylcholine vesicles
      (PSPC), thrombin-activated platelets, or umbilical vein endothelial cells
      influence inactivation of FIXa by PN-2/A beta PP. The Km of human or porcine FIXa
      activation of human factor X in the presence of PSPC, activated platelets, or
      endothelial cells in the absence or presence of thrombin-activated factor VIII
      (FVIIIa) was similar, (0.05-0.39 microM). The presence of FVIIIa increased the
      catalytic efficiency (kcat/Km ratio) of human and porcine factor IXa's activation
      of factor X 4952-406-fold, respectively. In the presence of PSPC, the Ki of human
      and porcine FIXa inhibition by PN-2/A beta PP was Ki = 1.9 x 10(-9) M and 5.8 x
      10(-9) M, respectively. After the addition of FVIIIa to the reaction, the Ki for
      both human and porcine FIXa inhibition by PN-2/A beta PP on PSPC increased 13-
      and 4-fold to Ki = 2.5 x 10(-8) M and 2.4 x 10(-8) M, respectively. These Ki for
      inhibition of human FIXa on phospholipid vesicles by PN-2/A beta PP were similar
      when factor X activation was measured by chromogenic or activation peptide
      release assays. FVIIIa reduced the inhibition of FIXa by PN-2/A beta PP only in
      the presence of PSPC.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7827068
TI  - Quantitative endoproteinase GluC footprinting of cooperative Ca2+ binding to
      calmodulin: proteolytic susceptibility of E31 and E87 indicates interdomain
      interactions.
AB  - Calmodulin is the primary eukaryotic intracellular calcium receptor. Cooperative
      calcium binding to two sites in each of two domains drives large conformational
      changes that enable it to activate target proteins. An understanding of the
      molecular mechanism of cooperativity requires determination of the conformational
      states populated by calmodulin, the intrinsic free energies of binding calcium to
      four sites, and the nature and degree of intradomain and interdomain
      interactions. To monitor residue-specific conformational changes within
      calmodulin as calcium binds, we have developed a new quantitative proteolytic
      footprinting method using endoproteinase GluC (EndoGluC). Under conditions of
      very limited proteolysis, cleavage occurred at only five of the sixteen positions
      possible in calmodulin. The relative abundance of fragments indicated that
      calcium induced changes in the susceptibility of individual peptide bonds.
      Quantitative susceptibility profiles were resolved for two positions: E31-L32, in
      site I in the N-terminal domain, and E87-A88, preceding site III in the C
      terminal domain. In apocalmodulin, E87-A88 was susceptible to EndoGluC; calcium
      binding to sites III and IV caused monotonic protection from proteolysis. The
      response of E31-L32 was biphasic. In apocalmodulin, it was resistant to cleavage.
      Susceptibility was induced by calcium binding to sites III and IV, followed by
      protection induced by calcium binding to sites I and II. This indicated that
      calmodulin must adopt at least three distinguishable conformations and suggested
      that the two domains interact. Model-dependent equilibrium constants were
      resolved from the EndoGluC susceptibility profiles for E31 and E87; they
      indicated cooperative binding within each domain. Approaches taken to validate
      this proteolytic footprinting method are described.

PMID- 7827069
TI  - Immunosuppressive activity of chemically synthesized gangliosides.
AB  - New chemical synthetic methods have permitted the synthesis of a spectrum of
      glycosphingolipid molecular species, some of which are not naturally occurring.
      Here we have studied a number of chemically synthesized gangliosides for
      immunosuppressive activity, using a human in vitro specific antigen (tetanus
      toxoid)-induced assay of the cellular immune response. Chemically synthesized GM3
      and GM4 had the same high degree of immunosuppressive activity as did natural GM3
      and GM4 gangliosides, verifying that inhibition is intrinsic to the ganglioside
      molecules and not caused by other molecules sometimes found in natural
      preparations (e.g., proteins). Studies of modified molecular species of GM3 and
      GM4, also prepared by chemical synthesis, have shown the influence of certain
      structural details upon the immunosuppressive activity of gangliosides: (i) the
      inverse relationship between fatty acyl chain length and immunosuppressive
      activity is extended to even shorter chain lengths, with the synthetic
      gangliosides d18:1-C2:0-GM3 and d18:1-C14:0-GM3 being more immunosuppressive than
      d18:1-C18:0-GM3 and d18:1-C24:0-GM3; (ii) hydroxylation of the fatty acyl group
      decreases immunosuppressive activity; (iii) substitution of an S-glycosidic bond
      for an O-glycosidic bond in the sialic acid ketosidic linkage in GM4 does not
      alter its activity; and (iv) modifications of the sialic acid group variably
      influence immunosuppressive activity, since KDN-GM3 and -GM4 ganglioside
      analogues, which contain a 3-deoxy-D-glycero-D-galacto-2-nonulopyranosonic acid
      in place of N-acetylneuraminic acid, retain activity, while other modifications
      such as 8-epi-GM3, and to a lesser extent 9-deoxy-GM3, reduce immunosuppressive
      activity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7827070
TI  - Identification of 9-cis,13-cis-retinoic acid as a major circulating retinoid in
      plasma.
AB  - In the course of measuring the concentrations of retinoic acids (RA) in bovine
      plasma, a major peak was observed which comigrated with 9-cis-RA on normal-phase
      high-performance liquid chromatography. Rechromatography of this retinoic on
      reverse-phase high-performance liquid chromatography showed that it was distinct
      from 9-cis-,13-cis-, and all-trans-RA, but comigrated with 9-cis,13-cis-retinoic
      acid (9,13-di-cis-RA). This retinoid was identified as 9,13-di-cis-RA based on
      its chemical, spectral, and chromatographic properties. Plasma concentrations of
      9,13-di-cis-RA increased from < or = 0.5 ng/mL at birth to 5-6 ng/mL by 48 h of
      age in the calf. The 9,13-di-cis-RA was also a major circulating product of 9-cis
      RA dosed intramuscularly to rats; conversely, intravenous administration of 9,13
      di-cis-RA produced circulating 9-cis-RA in the rat. 9,13-Di-cis-RA had little or
      no affinity for cellular retinoic acid binding protein types I and II. This study
      establishes 9,13-di-cis-RA as a naturally-occurring retinoid under physiological
      conditions, shows that it undergoes interconversion with 9-cis-RA, and emphasizes
      a need for careful chromatography to resolve 9-cis-RA and 9,13-di-cis-RA. This is
      consistent with in vivo 13-cis isomerization operating to modify the
      concentration and perhaps the activity of 9-cis-RA in vivo.

PMID- 7827071
TI  - Second derivative spectroscopy of enolase at high hydrostatic pressure: an
      approach to the study of macromolecular interactions.
AB  - Second derivative spectroscopy in the ultraviolet region of proteins has been
      used to study the polarity of the regions surrounding tyrosine residues. We show
      here that it can also be a tool to study the degree to which proteins associate
      and that it can be effectively combined with hydrostatic pressure in order to
      evaluate equilibrium dissociation constants and reaction volumes. Hydrostatic
      pressure causes yeast enolase to dissociate. Clear changes in the second
      derivative spectra of enolase were observed as pressure was increased. At enolase
      concentrations of about 20 microM, the midpoint of the transition is about 1800
      bar. All aspects of the transition are reversible up to 2700 bar. It is likely
      that the transition observed is the result of enolase dimers dissociating into
      monomers. The second derivative spectra indicate that one or more tyrosine
      residues is in an unusually polar environment in the dimer, an environment that
      is less polar in the monomer. Three tyrosines (6, 11, 130) are near the dimer
      interface. Tyrosines 6 and 11 are pointing into the water-filled crevice between
      the subunits and are close to several immobilized waters. All three are close to
      a network of intersubunit salt bridges and hydrogen bonds. We believe that the
      average tyrosine polarity in the dimer reflects the exposure of these tyrosines
      to immobilized water and the fixed dipole of the salt bridge. The water in the
      crevice between the subunits should be more mobile in the monomer; the salt
      bridge does not exist in the monomer.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7827072
TI  - Evidence for sub-picosecond heme doming in hemoglobin and myoglobin: a time
      resolved resonance Raman comparison of carbonmonoxy and deoxy species.
AB  - Separation of the photophysical aspects of the sub-picosecond (sub-ps) time
      resolved resonance Raman signal from contributions due to conformation has been
      achieved by comparing deoxyhemoglobin (Hb) in the T state with
      (carbonmonoxy)hemoglobin (HbCO), deoxy-beta 4 (beta 4 CO) (All R state), and
      monomers deoxymyoglobin and (carbonmonoxy)myoglobin (MbCO) [beta 4 consists of a
      tetramer of four beta-subunits and shows no cooperativity]. In all photolyzed
      species, Hb*(CO), Mb*(CO), and beta 4*(CO), the iron-histidine out-of-plane mode
      (vFe-His), indicative of heme doming, achieves 90% of its full intensity in 1 ps.
      The frequency of this mode (223-228 cm-1) is shifted significantly relative to
      equilibrium deoxy-Hb (210-216 cm-1) in the T state, but not with respect to
      either equilibrium deoxy-Mb or deoxy-beta 4. A correlation between the +12 cm-1
      bandshift of vFe-His and the -2 cm-1 shift of the electron density marker band
      (v4 at 1370 cm-1) relative to T-state deoxy-Hb is shown to hold on all time
      scales, including the sub-picosecond time scale. Photolyzed Hb*(CO) consists of R
      state or weakly interacting tetramers on the picosecond time scale and is shown
      to have properties similar to those of photolyzed Mb*(CO) and beta 4*(CO) on the
      picosecond time scale. These results establish that heme doming occurs as an
      ultrafast reaction to ligand dissociation and that heme doming is the primary
      event in the sequence of conformational changes leading to the cooperative R-->T
      transition.

PMID- 7827073
TI  - Roles of dipolar effects and local charge in the ionic strength dependence of
      redox reactions between c-type cytochromes.
AB  - Redox reactions between different c-type cytochromes were monitored by stopped
      flow spectroscopy. Second-order rate constants were determined at different ionic
      strengths for the reactions of Paracoccus denitrificans cytochrome c-551i with
      its physiologic redox partner cytochrome c-550, and with the nonphysiologic
      partner horse heart cytochrome c. The latter two cytochromes are structurally
      quite similar and exhibit identical redox potentials but bear net charges of -7
      and +7, respectively. Despite these opposite overall charges, the ionic strength
      dependencies for the reaction of each with the acidic cytochrome c-551i were very
      similar. The observed decrease in reaction rate with increasing ionic strength
      that was observed with cytochromes c-550 and c-551i, the latter of which bears a
      net charge of -20, cannot be explained simply on the basis of monopole-monopole
      interactions. These data were analyzed by two different methods: one which treats
      proteins as both monopoles and dipoles and considers the net charge; and another
      which neglects dipolar effects and considers only the local charge of the
      reactive site of the protein rather than net charge. The applicability of each
      method to the analysis of these data and to protein electrostatic interactions in
      general is discussed.

PMID- 7827074
TI  - Substrate-dependent competition of different P450 isozymes for limiting NADPH
      cytochrome P450 reductase.
AB  - The goal of these studies was to demonstrate that one P450 isozyme can influence
      the function of another isozyme when combined in a reconstituted system.
      Benzphetamine and 7-pentoxyresorufin were both shown to be preferred substrates
      for P450 2B4 (LM2) as compared to P450 1A2 (LM4). However, these substrates
      exhibited different characteristics when examined in reconstituted systems
      containing reductase and both P450 isozymes. Whereas benzphetamine demethylation
      showed a small increase in catalytic activity when both P450 1A2 and 2B4 were
      present over the activities obtained in simple reconstituted systems, 7
      pentoxyresorufin O-dealkylation (PROD) was dramatically inhibited when both
      isozymes were present. These results indicate that the functional interactions
      between P450s in complex reconstituted systems are dependent on the substrate
      present. Inhibition of PROD was also dependent on reductase levels, with the
      inhibitory effect being more pronounced at subsaturating reductase. Finally,
      these protein-protein interactions were shown to be dependent on the reductase
      concentration in the reconstituted system rather the P450 concentration,
      supporting the view that P450 1A2 is inhibiting the reaction by competing with
      P450 2B4 for reductase molecules.

PMID- 7827075
TI  - Solution structure of a green mamba toxin that activates muscarinic acetylcholine
      receptors, as studied by nuclear magnetic resonance and molecular modeling.
AB  - The three-dimensional solution structure of the MTX2 toxin (65 amino acids and 4
      disulfides) from the green mamba venom (Dendroaspis angusticeps), a toxin that
      activates the pharmacological M1 muscarinic acetylcholine receptors, has been
      determined by nuclear magnetic resonance and molecular modeling. Seventeen
      structures were calculated from 810 distance and 68 dihedral angle restraints
      using DIANA and X-PLOR. The average rms deviation between the 17 refined
      structures and the energy-minimized average structure is 0.95 A for the backbone
      atoms. The overall folding of MTX2 consists of three loops stabilized by the four
      disulfides and forming a two- and a three-stranded beta-sheet. This structure
      appears to be very similar to that of other snake toxins, such as neurotoxins,
      fasciculins, and cardiotoxins, that also possess the same three-finger fold. For
      instance, the RMSd for the backbone atoms between MTX2 and the curaremimetic
      toxin alpha (from Naja nigricollis), the acetylcholinesterase inhibitor
      fasciculin 1 (from Dendroaspis angusticeps), and the cardiotoxic toxin gamma
      (from Naja nigricollis) are 1.86, 1.87, and 2.04 A, respectively. Local
      differences are observed between this toxin and the other structurally related
      toxins. Some of these differences could be relevant for the functional
      specificity of MTX2. In particular, this toxin presents a large twist at the tip
      of loop II due to a bulge (V31, T32; N35) that accommodates an inserted amino
      acid in the loop. This spatial arrangement brings the side chain of K34 in the
      beta-turn of the loop to be aligned with the beta-sheet. Hypotheses about a
      possible functional role of this lysine are described. Other characteristics in
      the side-chain distribution that could be related to the MTX2 function are
      presented.

PMID- 7827076
TI  - Characterization of the promoter regulatory region of the human pyruvate
      dehydrogenase beta gene.
AB  - A genomic clone (19 kb) harboring the intron-exon sequences and the promoter
      regulatory region of the E1 beta gene of human pyruvate dehydrogenase complex was
      isolated by screening a placental genomic library. The nucleotide sequence of the
      promoter region (1245 bp) showed 18 differences (including mismatches,
      insertions, and deletions) as compared to the published sequence [Koike et al.
      (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 5594-5597]. The E1 beta promoter lacked
      a TATA box homology but contained initiator sequences (two) and Sp1 sites (three)
      which are frequently found in TATA-less promoters. The DNase I footprinting
      pattern of the promoter region with crude rat liver nuclear extracts showed at
      least seven regions of protein binding and nuclease protection (P1-P7). The DNase
      I protected regions contained consensus nucleotide sequences recognized by GATA
      1, Sp1, IgNF-A, Lva, bicoid Q9, NF-kB, HNF-5, H4TF-1, WAP5, and ADH transription
      factors. Transient expression of chloramphenicol acetyltransferase (CAT)
      suggested the possible presence of negative elements located within the sequence
      from -2316 to -930, whereas deletion constructs containing -929 to +32 and -98 to
      +32 DNA sequences showed approximately 7- and 20-fold increases in CAT activity
      over the basal CAT activity. Additional studies indicated the presence of an
      orientation-dependent cis element (or elements) within the region from -282 to 
      397 that acts as an enhancer or a repressor upon a heterologous thymidine kinase
      promoter.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7827077
TI  - Solution conformation of the (-)-trans-anti-benzo[c]phenanthrene-dA ([BPh]dA)
      adduct opposite dT in a DNA duplex: intercalation of the covalently attached
      benzo[c]phenanthrenyl ring to the 3'-side of the adduct site and comparison with
      the (+)-trans-anti-[BPh]dA opposite dT stereoisomer.
AB  - This paper reports on NMR-molecular mechanics structural studies of the (-)-
      trans-anti-benzo[c]phenanthrene-dA adduct positioned opposite dT in the sequence
      context of the d(C1-T2-C3-T4-C5-[BPh]A6-C7-T8-T9-C10-C11).d(G12- G13-A14-A15-G16
      T17-G18-A19-G20-A21- G22) duplex (designated as the (-)-trans-anti-[BPh]dA.dT 11
      mer duplex). This adduct is derived from the covalent binding of (-)-1,2
      dihydroxy-3,4-epoxy-1,2,3,4-tetrahydro-benzo[c]phenanthrene [(-)-anti-BPhDE] to
      N6 of dA6 in this duplex sequence. The benzo[c]phenanthrenyl and nucleic acid
      exchangeable and nonexchangeable protons were assigned in the predominant
      conformation following analysis of two-dimensional NMR data sets in H2O and D2O
      buffer solution. The solution structure of the (-)-trans-anti-[BPh]dA.dT 11-mer
      duplex has been determined by incorporating intramolecular and carcinogen-DNA
      proton-proton distances defined by lower and upper bounds deduced from NOESY data
      sets as restraints in molecular mechanics computations in torsion angle space.
      The results show that the [BPh]dA6.dT17 base pair propeller twists and buckles
      slightly to permit the covalently attached benzo[c]phenanthrenyl ring to
      intercalate between the [BPh]dA6.dT17 and dC7.dG16 base pairs to the 3'-side of
      the [BPh]dA6 lesion site without disrupting the Watson-Crick hydrogen bond
      alignments in the modified duplex. The strain in the highly sterically hindered
      fjord region of the benzo[c]phenanthrenyl moiety is relieved by the propeller
      like nonplanar geometry of the aromatic phenanthrenyl ring system, which stacks
      predominantly with the dG16 and dT17 bases on the unmodified strand. The benzylic
      ring adopts a distorted half-chair form, in which the H1 and H2 protons are
      pseudo-diequatorial and the H3 and H4 protons are pseudodiaxial. The current
      observation that the (-)-trans-anti-[BPh]dA positioned opposite dT intercalates
      to the 3'-side of the intact modified base pair contrasts with our previous
      demonstration that the stereoisomeric (+)-trans-anti-[BPh]dA adduct positioned
      opposite dT intercalates to the 5'-side of the intact modified base pair [Cosman,
      M., et al. (1993b) Biochemistry 32, 12488-12497]. These stereochemically induced
      structural differences between isomeric [BPh]dA lesions derived from the binding
      of chiral (+)- and (-)-anti-BPhDE enantiomers may in turn profoundly influence
      the interactions of the carcinogen-modified DNA with repair and replication
      enzymes in the cell.

PMID- 7827078
TI  - Systematic analysis of the Saccharomyces cerevisiae alpha-factor containing
      lactam constraints of different ring size.
AB  - Eight cyclic analogs and corresponding linear homologs of the alpha-factor mating
      pheromone (WHWLQLKPGQPMY) of Saccharomyces cerevisiae were synthesized using
      solid-phase procedures on a phenylacetamidomethyl support. On-resin lactamization
      of the side chains of residues 7 and 10 to form rings containing from 14 to 18
      atoms was effected by the BOP reagent. All peptides were highly homogeneous and
      gave expected molecular ions by FAB mass spectrometry. The constrained analogs
      had biological activities varying from 10% to less than 0.1% of that of [Nle12]
      alpha-factor. In all cases, cyclic analogs with Glu in position 10 were more
      active than the homolog with Asp at this position. This trend was also found with
      the corresponding linear pheromones, suggesting that a gamma-carbonyl in position
      10 is an important determinant of pheromone potency. The cyclic peptides had from
      50- to 20000-fold lower affinities for the alpha-factor receptor than for [Nle12]
      alpha-factor, as judged using a competition binding assay. Circular dichroism
      studies indicate that the cyclic lactam-containing region of cyclo7.10[Orn7,
      Glu10,Nle12]-alpha-factor retains a beta-turn-like structure similar to that
      found in the corresponding model tetrapeptide. The results show that covalently
      constrained analogs of the linear pheromone can maintain biological activity,
      despite binding poorly to the receptor, and indicate that a beta-turn-like
      structure in the center of the pheromone allows signal transduction.

PMID- 7827079
TI  - Differential binding of nicotine and alpha-bungarotoxin to residues 173-204 of
      the nicotinic acetylcholine receptor alpha 1 subunit.
AB  - The binding of the agonist L-[3H]nicotine and the competitive antagonist alpha
      [125I]bungarotoxin to synthetic peptides comprising residues 173-227 of the
      Torpedo nicotinic acetylcholine receptor alpha subunit were compared using a
      solid phase-assay. Equilibrium saturation binding of [3H]nicotine to peptide 173
      204 revealed a minor binding component with an apparent KD of 1.9 nM and a major
      component with a KD of 1.6 microM. Nicotine bound to alpha subunit peptides 173
      204, 181-198, and 194-204 and less well to 179-192 and 186-196, and it did not
      bind to 173-180 and 205-227. alpha-Bungarotoxin bound to peptides 173-204 and 186
      196 and less well to 179-192 and 181-198, and it did not bind to 173-180, 194
      204, and 205-227. Agonists (nicotine, suberyldicholine, carbamylcholine, and
      cytisine) effectively competed [3H]nicotine binding to the 173-204 peptide but
      competed alpha-[125I]bungarotoxin binding at millimolar concentration and with
      loss of rank order of potency. The competitive antagonists alpha-bungarotoxin,
      alpha-cobratoxin, and d-tubocurarine effectively blocked alpha-[125I]bungarotoxin
      binding but competed [3H]nicotine binding only at millimolar concentration. These
      results indicate that nicotine and alpha-bungarotoxin preferentially bind to
      different determinants within residues 173-204. Alternatively, nicotine and alpha
      bungarotoxin could bind to different conformations of the peptide. Both agents
      appear to interact with common residues, most likely Tyr 190 and Cys 192, in the
      region of Cys 192 so that there is overlap of binding sites.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7827080
TI  - Compartmentation of glucose and fructose 1,6-bisphosphate metabolism in vascular
      smooth muscle.
AB  - We examined the metabolism of exogenously added 13C-labeled fructose 1,6
      bisphosphate (either labeled at the first and sixth carbons or labeled at the
      first carbon only) and of [2-13C]glucose in well-oxygenated and well-superfused
      hog carotid artery segments. Exogenously added fructose 1,6-bisphosphate was
      utilized by hog carotid artery and primarily participated in gluconeogenesis
      while the production of [3-13C]lactate was not significantly different from zero.
      When [1,6-13C]fructose 1,6-bisphosphate or [1-13C]fructose 1,6-bisphosphate was
      utilized individually, gluconeogenic flux occurred without metabolism through
      aldolase and triosephosphate isomerase resulting in formation of [1,6-13C]
      glucose and [1-13C]glucose respectively. When [2-13C]glucose was the sole
      exogenous substrate, it was utilized and exclusively participated in glycolytic
      flux with production of [3-13C]lactate and no gluconeogenic flux from the trioses
      to [5-13C]glucose. When both glucose and fructose 1,6-bisphosphate were provided
      together as exogenous substrates, glucose still participated exclusively in
      glycolytic flux with no trioses participating in gluconeogenesis while fructose
      1,6-bisphosphate participated in glycolytic flux with [3-13C]lactate production
      approximately being approximately half of the [1,6-13C]glucose production from
      [1,6-13C]fructose 1,6-bisphosphate. In the presence of glucose, [1-13C]fructose
      1,6-bisphosphate also participated in glycolytic flux and gluconeogenic flux
      simultaneously. However in the presence of [2-13C]glucose, [1-13C]fructose 1,6
      bisphosphate underwent isomerization through the trioses prior to gluconeogenesis
      since [6-13C]glucose was produced.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7827081
TI  - Regulation of microtubule dynamic instability by tubulin-GDP.
AB  - The regulation of the spontaneous transitions between growth and shortening of
      microtubules is central to the biological function of dynamic instability. Here
      we examine the effects of controlled amounts of tubulin-GDP (Tu-GDP) on the
      dynamic properties of microtubules in vitro. The transphosphorylation equilibrium
      between GTP, GDP, UTP, and UDP in the presence of nucleoside-5'-diphosphate
      kinase (NDPK) was used to fix the ratio chi D = [Tu-GDP]/([Tu-GTP]) + [Tu-GDP])
      in solution. Lower levels of Tu-GDP (chi D < 0.6) produce only a small increase
      in the apparent critical concentration, Cc'. However, at chi D > 0.6 a dramatic
      increase in Cc is observed. At steady state of assembly, low levels of Tu-GDP
      (chi D < 0.5) cause a significant reduction of the dynamic length redistribution
      of the microtubule population. The principal observable effect of Tu-GDP on the
      empirical parameters of microtubule dynamic instability is to decrease the
      duration of individual phases of microtubule growth and shortening, with
      relatively little effect on the intrinsic rates of growth and shortening.
      Observations in dark-field video microscopy reveal that the irregularities in the
      rates of growth (and shortening) are increased in the presence of Tu-GDP. At
      elevated levels of Tu-GDP, pauses occur frequently during the growth phase,
      microtubule dynamics cease to conform to a clear two-phase process, and the
      extents of growth and shortening excursions are strongly attenuated. The
      experimental results are well reproduced by computer simulation, using mechanisms
      defined in the lateral cap model for dynamic instability [Martin, S. R.,
      Schilstra, M. J., & Bayley, P. M. (1993) Biophys. J. 65, 578-596], which includes
      the binding of Tu-GDP to the microtubule end in competition with Tu-GTP. In the
      presence of Tu-GDP, the growing-state lifetime is significantly attenuated, and
      the microtubule length versus time excursions simulated by the model show
      irregularities and complex multistate behavior, including pauses, as observed
      experimentally. These results suggest that Tu-GDP can modulate microtubule
      dynamics significantly under conditions where little bulk microtubule disassembly
      is induced. Tu-GDP therefore appears to exemplify the action of a relatively
      simple factor with the potential capability for regulation of microtubule
      dynamics in a cellular environment.

PMID- 7827082
TI  - Mammalian protein geranylgeranyltransferase-I: substrate specificity, kinetic
      mechanism, metal requirements, and affinity labeling.
AB  - Protein geranylgeranyltransferase-I (PGGT-I) catalyzes the transfer of the 20
      carbon prenyl group from geranylgeranyl pyrophosphate to the cysteine residue
      near the C-termini of a variety of eukaryotic proteins. Kinetic analysis of
      homogenous PGGT-I from bovine brain reveals that the reaction follows a
      sequential pathway in which either prenyl donor or acceptor can bind first to the
      enzyme and that the reaction operates at steady-state rather than at rapid
      equilibrium. Substrate inhibition by prenyl acceptor but not by prenyl donor
      suggests that geranylgeranyl pyrophosphate binding first to free enzyme is the
      kinetically preferred pathway. This is supported by isotope trapping experiments
      which show that the ternary complex goes on to products faster than the release
      of geranylgeranyl pyrophosphate from the complex. The KM for the interaction of
      geranylgeranyl pyrophosphate with PGGT-I is markedly affected by the structure of
      the prenyl acceptor bound to the enzyme. A detailed analysis of the substrate
      specificity of PGGT-I reveals that peptides which contain a C-terminal leucine
      are preferred (kcat/KM = 1-5 x 10(5) M-1 s-1) to those that end in serine
      (kcat/KM = 2-4 x 10(3) M-1 s-1) or phenylalanine (kcat/KM = 0.5 x 10(3) M-1 s-1).
      PGGT-I also catalyzes the farnesylation of peptides that have a C-terminal
      leucine; kcat for farnesylation and KM for farnesyl pyrophosphate are similar to
      those for geranylgeranylation, but the KM for the peptide is 30-fold higher.
      Geranyl pyrophosphate is utilized by PGGT-I but is a poor substrate. Optimal
      activity of PGGT-I is obtained in the presence of micromolar amounts of Zn2+ and
      mM amounts of Mg2+. Mn2+ or Cd2+ but not Co2+ can substitute for Zn2+ and for
      Mg2+. Metals are not required for tight-binding of geranylgeranyl pyrophosphate
      to PGGT-I, and the measured dissociation equilibrium constant for this binary
      complex is 16 nM. Photoaffinity analogues of geranylgeranyl pyrophosphate and
      farnesyl pyrophosphate were prepared and shown to exclusively label the beta
      subunit. The implication of the results for the substrate specificity of protein
      prenylation in cells is briefly discussed.

PMID- 7827083
TI  - Dynamics of parvalbumin studied by fluorescence emission and triplet absorption
      spectroscopy of tryptophan.
AB  - Fluorescence emission and triplet-triplet absorbance spectroscopy of the single
      tryptophan in cod parvalbumin were used to study the stability and dynamics of
      the protein as influenced by Ca2+ binding and interaction with a chaotropic
      agent. The concentrations for half-saturation for Ca binding were 3.6 x 10(-9),
      3.3 x 10(-4), 7.1 x 10(-3), and 0.14 M in the presence of 0, 2, 3, and 4 M
      guanidine hydrochloride, respectively. As predicted for thermodynamic
      reversibility, the guanidine hydrochloride unfolding reaction depends upon Ca2+,
      and the delta G are as follows: 22.9, 29.3, 35.2, and 44.2 kJ/mol for no added
      Ca2+, 1, 2, and 5 mM Ca2+, respectively. The stability toward denaturation
      imparted by the binding of two Ca2+ is about -60 kJ/mol. For Ca(2+)-bound
      parvalbumin in the presence of excess Ca2+, the decay of the triplet state
      tryptophan is approximately exponential, and the lifetime decreases from 6.5 to
      3.8 ms as the temperature increases from 10 to 40 degrees C. In contrast, the
      triplet decay of the calcium-free protein is nonexponential over the time range
      of microseconds to milliseconds, a result that may indicate that the Ca-free
      protein is molten-globule-like. At Ca2+ concentrations where the protein is
      partially saturated with Ca2+, the lifetime of the longest decay component is
      less than that for the Ca-saturated protein; this finding suggests an exchange of
      Ca2+ and a conformational change during the triplet lifetime. From these data, a
      rate constant for the process that includes calcium-related protein
      conformational change can be surmised to range between 200 and 500 s-1.

PMID- 7827084
TI  - NMR solution structure of a nonanucleotide duplex with a dG mismatch opposite a
      10R adduct derived from trans addition of a deoxyadenosine N6-amino group to (-)
      (7S,8R,9R,10S)-7,8-dihydroxy-9,10-epoxy-7,8,9,10- tetrahydrobenzo[a]pyrene.
AB  - A nonanucleotide in which (-)-(7S,8R,9R,10S)-7,8-dihydroxy-9,10-epoxy- 7,8,9,10
      tetrahydrobenzo[a]pyrene (7-hydroxy group and epoxide oxygen are trans) is
      covalently bonded to the exocyclic N6-amino group of deoxyadenosine through trans
      addition at C10 of the epoxide (10R adduct) has been synthesized. The modified
      oligonucleotide d(GGTCA*CGAG) was incorporated into the duplex
      d(GGTCA*CGAG).d(CTCGGGACC), containing a dG mismatch opposite the modified base
      (dA*). Proton assignments for the solution structure of the duplex containing the
      10R adduct were made using 2D TOCSY and NOESY NMR spectra. The complete hybrid
      relaxation matrix program, MORASS2.0, was used to generate NOESY distance
      constraints for iterative refinement using distance-restrained molecular dynamics
      calculations with AMBER4.0. The iteratively refined structure showed the
      hydrocarbon intercalated from the major groove immediately below the dC4-dG15
      base pair and oriented toward the 5'-end of the modified strand. The modified dA
      is in an anti configuration, with the dG of the GA mismatch turned out into the
      major groove. Chemical shifts of the hydrocarbon protons and unusual chemical
      shifts of sugar protons were accounted for by this orientation of the adduct. The
      information available currently provides the foundation for the rational
      explanation of observed benzo[a]pyrene (BaP) structures and predictions for other
      BaP dG and dA adducts.

PMID- 7827085
TI  - Role of magnesium ion in mithramycin-DNA interaction: binding of mithramycin-Mg2+
      complexes with DNA.
AB  - Mithramycin is an anticancer drug that blocks macromolecular synthesis via
      reversible interaction with the DNA template in the presence of bivalent metal
      ions such as Mg2+. The role of Mg2+ in this antibiotic-DNA interaction is not
      clear. We approached the problem in two steps via studies on the interactions
      between (i) mithramycin and Mg2+ and (ii) mithramycin-Mg2+ complex(es) and DNA.
      Spectroscopic techniques such as absorption, fluorescence, and CD were employed
      for the purpose. From equilibrium and kinetic studies, we earlier reported that
      MTR forms two different types of complexes with Mg2+ [Aich, P., & Dasgupta, D.
      (1990) Biochem. Biophys. Res. Commun. 173, 689]. The two complexes are referred
      to as complex I (with 1:1 stoichiometry in terms of mithramycin: Mg2+) and
      complex II (with 2:1 stoichiometry in terms of mithramycin: Mg2+). In this
      report, we have further characterized these complexes by fluorescence
      spectroscopy. Interactions of these complexes with calf thymus DNA were examined
      to elucidate their binding. Evaluation of binding parameters (intrinsic binding
      constant and stoichiometry) from spectrophotometric and fluorimetric titrations
      suggests that the complexes bind differently to the same DNA. Measurement of
      van't Hoff enthalpies for the interaction of the two ligands and DNA shows that
      the complex I-DNA interaction is exothermic, in contrast to the endothermic
      nature of the complex II-DNA interaction. This could originate from a difference
      in the molecular nature of the interactions between the complexes and calf thymus
      DNA. Our studies to detect the nature of the groove via which these complexes
      bind to DNA suggest that both complexes approach via the minor groove of the
      DNA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7827086
TI  - Preparation and characterization of a deoxyoligonucleotide 49-mer containing a
      site-specific thymidylyl-(3',5')-deoxyadenosine photoproduct.
AB  - Irradiation of d(GTATTATG) with 254 nm light gave rise to four major
      photoproducts, two of which were readily identified by NMR as the cis-syn
      cyclobutane dimer and the (6-4) photoproduct of the central TT site. Analysis of
      the NMR data for the other two photoproducts indicated that they were not any of
      the other known photoproducts of a TT site and might be TA* photoproducts [Bose,
      S. N., et al. (1983) Science 220, 723-725]. In support of this possibility, the
      fluorescence spectra of the products of acid hydrolysis of the two photoproducts
      were very similar to that reported for the hydrolysis product of the TA*
      photoproduct of TpdA. Only one of the two TA*-containing octamers could be
      ligated at both ends to form a 49-mer oligonucleotide in the presence of a
      complementary oligonucleotide scaffold, suggesting that the TA* photoproduct had
      formed between T5 and A6. The position of the TA* photoproduct was confirmed by
      mapping the arrest sites for 3'-->5' exonucleolytic degradation of the 49-mer by
      T4 DNA polymerase and for primer extension opposite the 49-mer by exonuclease
      deficient Klenow fragment (KF) and Sequenase Version 2.0. The TA* product could
      also be bypassed by both polymerases, but it was less of a block to KF. Treatment
      with 1 M aqueous piperidine at 100 degrees C led to a maximum of about 34%
      cleavage of the DNA at the site of the TA* product.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7827087
TI  - K(+)-ribosome interactions determine the large enhancements of 39K NMR transverse
      relaxation rates in the cytoplasm of Escherichia coli K-12.
AB  - As a probe of physical chemical properties of the intracellular environment, we
      measured 39K NMR transverse relaxation rates in concentrated cell slurries of
      Escherichia coli K-12 grown in minimal medium over a range of osmolarities (from
      0.1 to 1.0 OsM) and after plasmolysis. The 39K transverse relaxation at a
      resonance frequency of approximately 18.67 MHz is biexponential under all
      conditions, and 100% of the expected signal intensity is detected. Both
      components of the 39K NMR transverse relaxation are very fast, and the difference
      between the fast and slow relaxation rates is very large compared to previous
      measurements on 23Na and 39K in protein and nucleic acid solutions in vitro. The
      39K transverse relaxation rates decrease as the osmolarity of the growth media
      increases but increase dramatically when cells grown in 0.1 OsM media are
      plasmolyzed at 1.0 OsM. The homogeneous nature and the 100% visibility of the 39K
      signal indicate the existence of fast exchange among the multiple, magnetically
      distinguishable populations of 39K which probably exist in the cytoplasm. The
      absence of static quadrupolar splitting of the cytoplasmic 39K signal (as
      indicated by a single peak in the spectrum) indicates that the cytoplasm, as
      probed by 39K NMR, behaves like a concentrated but isotropic nucleic acid
      solution rather than an anisotropic nucleic acid liquid crystal. To understand
      the origins of the striking NMR relaxation behavior of 39K in viable cells, we
      have investigated NMR transverse relaxation rates of 39K (and also 23Na and 35Cl)
      in E. coli 50S and 70S ribosome solutions in vitro. At concentrations of ions and
      of ribosomes that to the extent possible mimic those of the cytoplasm of E. coli,
      we find that 39K, 23Na, and 35Cl transverse relaxation rates all exhibit
      biexponential behavior, and 39K and 23Na exhibit the large magnitudes and the
      large difference between the slow and the fast relaxation rates observed in
      viable cells. These polyanionic ribosome solutions are the only in vitro model
      system discovered to date that exhibits 39K transverse relaxation rates
      comparable to those in viable cells. We conclude that K(+)-ribosome interactions
      are the dominant source of the NMR properties of K+ in E. coli.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7827088
TI  - Crystal structure, folding, and operator binding of the hyperstable Arc repressor
      mutant PL8.
AB  - Arc repressor is a small, dimeric DNA-binding protein that belongs to the ribbon
      helix-helix family of transcription factors. Replacing Pro8 at the N-terminal end
      of the beta-sheet with leucine increases the stability of the mutant protein by
      2.5 kcal/mol of dimer. However, this enhanced stability is achieved at the
      expense of significantly reduced DNA binding affinity. The structure of the PL8
      mutant dimer has been determined to 2.4-A resolution by X-ray crystallography.
      The overall structure of the mutant is very similar to wild type, but Leu8 makes
      an additional interstrand hydrogen bond at each end of the beta-sheet of the
      mutant, increasing the total number of beta-sheet hydrogen bonds from six to
      eight. Comparison of the refolding and unfolding kinetics of the PL8 mutant and
      wild-type Arc shows that the enhanced stability of the mutant is accounted for by
      a decrease in the rate of protein unfolding, suggesting that the mutation acts to
      stabilize the native state and that the beta-sheet forms after the rate-limiting
      step in folding. The reduced operator affinity of the PL8 dimer appears to arise
      because the mutant cannot make the new interstrand hydrogen bonds and
      simultaneously make the wild-type set of contacts with operator DNA.

PMID- 7827089
TI  - Three-dimensional solution structure of the N-terminal receiver domain of NTRC.
AB  - NTRC is a transcriptional enhancer binding protein whose N-terminal domain is a
      member of the family of receiver domains of two-component regulatory systems.
      Using 3D and 4D NMR spectroscopy, we have completed the 1H, 15N, and 13C
      assignments and determined the solution structure of the N-terminal receiver
      domain of the NTRC protein. Determination of the three-dimensional structure was
      carried out with the program X-PLOR (Brunger, 1992) using a total of 915 NMR
      derived distance and dihedral angle restraints. The resultant family of
      structures has an average root mean square deviation of 0.81 A from the average
      structure for the backbone atoms involved in well-defined secondary structure.
      The structure is comprised of five alpha-helices and a five-stranded parallel
      beta-sheet, in a (beta/alpha)5 topology. Comparison of the solution structure of
      the NTRC receiver domain with the crystal structures of the homologous protein
      CheY in both the Mg(2+)-free and Mg(2+)-bound forms [Stock, A.M., Mottonen, J.
      M., Stock, J. B., & Schutt, C. E. (1989) Nature 337, 745-749; Volz, K., &
      Matsumura, P. (1991) J. Biol. Chem. 296, 15511-15519; Stock, A. M., Martinez
      Hackert, E., Rasmussen, B. F., West, A. H., Stock, J. B., Ringe, D., & Petsko, G.
      A. (1993) Biochemistry 32, 13375-13380; Bellsolell, L., Prieto, J., Serrano, L.,
      & Coll, M. (1994) J. Mol. Biol. 238, 489-495] reveals a very similar fold, with
      the only significant difference occurring in the positioning of helix 4 relative
      to the rest of the protein. Examination of the conformation of consensus residues
      of the receiver domain superfamily [Volz, K. (1993) Biochemistry 32, 11741-11753]
      in the structures of the NTRC receiver domain and CheY establishes the structural
      importance of residues whose side chains are involved in hydrogen bonding or
      hydrophobic core interactions. The importance of some nonconsensus residues which
      may be conserved for their ability to fulfill helix capping roles is also
      discussed.

PMID- 7827090
TI  - NMR constraints on the location of the retinal chromophore in rhodopsin and
      bathorhodopsin.
AB  - Rhodopsin is the photoreceptor in vertebrate rod cells responsible for vision at
      low light intensities. The photoreactive chromophore in rhodopsin is 11-cis
      retinal bound to the protein via a protonated Schiff base with Glu113 as the
      counterion. We have used the observed 13C NMR chemical shifts of the conjugated
      retinal carbons in combination with semiempirical molecular orbital calculations
      to establish the major charge interactions in the retinal binding site of
      rhodopsin and its primary photoproduct, bathorhodopsin. In rhodopsin, the NMR
      data constrain one of the carboxylate oxygens (O1) of Glu113 to be approximately
      3 A from the C12 position of the retinal with the second oxygen oriented away
      from the conjugated retinal chain. The O1-C12-H angle is constrained by taking
      into account the 500 nm absorption maximum of the protein-bound retinal as well
      as the chemical shift data. The bathorhodopsin retinal binding site structure is
      generated from the rhodopsin model by isomerization of the C11 = C12 bond and
      incorporation of C-C single bond twists from C8 to C15. The resulting structure
      yields a moderate fit to both the chemical shift data and the 543 nm absorption
      maximum of bathorhodopsin. In both the rhodopsin and bathorhodopsin models, we
      have included a structural water molecule hydrogen bonded with the Schiff base to
      account for the high C = N stretching vibrations previously observed.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7827091
TI  - In vivo glycation of aldehyde reductase, a major 3-deoxyglucosone reducing
      enzyme: identification of glycation sites.
AB  - We have reported that the enzyme which reduces 3-deoxyglucosone (3-DG), a major
      intermediate and a potent cross-linker in the Maillard reaction, is identical
      with aldehyde reductase [Takahashi, M., Fujii, J., Teshima, T., Suzuki, K.,
      Shiba, T., & Taniguchi, N. (1993) Gene 127, 249-253]. The enzyme purified from
      normal rat liver was found to be partially glycated as judged by binding to a
      boronate column and reactivity to anti-epsilon-hexitol lysine IgG. Sites of in
      vivo glycation of rat liver aldehyde reductase were identified by sequencing of
      digested peptides labeled with NaB[3H]4 and by mass spectrometry. The major
      glycated sites were lysines 67, 84, and 140. The glycated enzyme had low
      catalytic efficiency (kcat/Km) as compared to the nonglycated form. In
      streptozotocin-induced diabetic rats, the glycated form was significantly
      increased in kidneys. Because the enzyme plays a role in detoxifying 3-DG formed
      through the Maillard reaction in vivo, glycation of aldehyde reductase and
      reduction of its activity may result in the metabolic imbalance under diabetic
      conditions.

PMID- 7827092
TI  - A mechlorethamine-induced DNA interstrand cross-link bends duplex DNA.
AB  - The dG-to-dG, DNA-DNA interstrand cross-link at the duplex sequence 5'-d(GNC)
      formed by the antitumor drug mechlorethamine (bis(2-chloroethyl)methylamine) was
      studied both theoretically and experimentally. Computer models of cross-linked
      DNA were energy minimized using molecular mechanics. The energy minimized
      structures possessed local distortion of the DNA helix, especially propeller
      twisting and buckling, caused by the tether length being too small to bridge the
      spacing of N7 atoms of dG at the sequence 5'-d(GNC) in B DNA. Overwinding of 2-6
      degrees was present at each of the two dinucleotide steps spanned by the cross
      link. The predicted structural changes were compatible with the possibility that
      this cross-link would introduce a static bend into the DNA double helix axis. An
      experimental study provided evidence for this induced bending of the helix axis
      in interstrand cross-linked samples. DNAs containing multiple mechlorethamine
      induced interstrand cross-links exhibited anomalously low electrophoretic
      mobility in polyacrylamide gels when the lesions were separated by one or two
      turns. From the degree of gel retardation, the cross-linked DNAs were estimated
      to be bent by 12.4-16.8 degrees per lesion; estimation of the extent to which
      this bend was induced by the lesion was complicated by a preexisting bend in the
      non-cross-linked DNAs used. The data did not allow distinction of a static from
      an anisotropic dynamic bend; "universal" and "hinge" joints were excluded.
      Anomalous mobility was maximal when the lesion spacing was 21 bp, suggesting a
      helical repeat of 10.5 bp per turn.

PMID- 7827093
TI  - Duration and amplitude of the light-induced cGMP hydrolysis in vertebrate
      photoreceptors are regulated by multiple phosphorylation of rhodopsin and by
      arrestin binding.
AB  - The duration and amplitude of the light-induced cGMP hydrolysis in bovine rod
      outer segments were investigated using purified rhodopsin in nine different
      states of phosphorylation in a reconstituted system. Effects of varying amounts
      of arrestin at all states of rhodopsin phosphorylation were measured. The
      findings were the following: (1) At low bleaching levels, the activity of
      phosphodigesterase (PDE) depends strongly on the phosphorylation degree of the
      light-activated rhodopsin (R*), while at saturating light levels R* of all
      phosphorylation degrees activates PDE to the same extent. (2) The turnoff time
      for PDE is markedly shortened if R* is phosphorylated, independent of the number
      of phosphate groups incorporated into rhodopsin (P/R); i.e., the first phosphate
      which is bound to R* seems to be responsible for the shortened turnoff time. The
      lifetime of phosphorylated R* is shown to be dramatically reduced compared to
      that of unphosphorylated R*, as monitored by the ability of R* to activate PDE.
      (3) After activation with phosphorylated R*, addition of arrestin caused a
      further reduction of both the maximum activity and the turnoff time of PDE. Both
      effects were strongly dependent on (a) the phosphorylation degree of R*, (b) the
      concentration of arrestin, and (c) the concentration of R*. These results suggest
      that the light-induced phosphorylation of rhodopsin to different extents and the
      subsequent binding of arrestin are involved in the light adaptation and in the
      fine regulation of the light response in vertebrate photoreceptors.

PMID- 7827094
TI  - Mutant Glu781-->Ala of the rat kidney Na+,K(+)-ATPase displays low cation
      affinity and catalyzes ATP hydrolysis at a high rate in the absence of potassium
      ions.
AB  - Site-specific mutagenesis was used to replace Glu329, Glu781, Asp806, Thr809, and
      Asp810 in the transmembrane domain of the ouabain-insensitive alpha 1-isoform of
      rat kidney Na+,K(+)-ATPase. cDNAs encoding any of the mutants Glu329-->Ala,
      Glu781-->Ala, Asp806-->Asn, Thr809-->Ala, and Asp810-->Asn were transfected into
      COS cells, and transfectants were grown in the presence of ouabain to inhibit the
      endogenous COS cell Na+,K(+)-ATPase. Mutants Glu781-->Ala and Thr809-->Ala were
      functional as evidenced by their ability to confer ouabain resistance to the
      cells, whereas mutants Glu329-->Ala, Asp806-->Asn, and Asp810-->Asn were
      inactive. The apparent Na+ affinities determined by titrations of Na+,K(+)-ATPase
      activity, Na(+)-ATPase activity, and phosphorylation from ATP in mutants Glu781-
      >Ala and Thr809-->Ala were strongly reduced relative to the affinity of the wild
      type (6-8-fold increase in K0.5 for Na+ in the phosphorylation assay for both
      mutants). The Glu781-->Ala mutant displayed a 3-4-fold reduction in the apparent
      affinity for K+ and was able to hydrolyze ATP at a high rate in the absence of K+
      (Vmax for Na(+)-ATPase activity 5-fold higher than that of the wild-type enzyme).
      The steady-state phosphoenzyme level formed by the Glu781-->Ala mutant was
      increased 3-fold by addition of oligomycin, whereas only a slight effect of
      oligomycin was observed for mutant Thr809-->Ala and the wild type.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7827095
TI  - Analysis of the mechanism of assembly of cleaved barnase from two peptide
      fragments and its relevance to the folding pathway of uncleaved barnase.
AB  - A peptide corresponding to residues 1-22 of barnase that contains its major alpha
      helix (residues 6-18) binds rapidly to the complementary peptide (residues 23
      110) to form a catalytically active complex with near-native structure. Peptide 1
      22 is approximately 3% helical in aqueous solution at 25 degrees C. A set of
      mutations in the helical regions of (1-22) cause the helix to be destabilized. We
      have investigated the mechanism of assembly of the peptides by analyzing the
      kinetics and equilibria of association of those mutants of (1-22) with native (23
      110). The association reaction follows second-order kinetics. Virtually all the
      change in stability of the complex on mutation is reflected in changes in the
      association rate constant with the dissociation rate constant being very little
      affected. Both Bronsted and theta-value analyses show that the helix is
      essentially fully formed in the transition state for the association at all the
      positions probed (residues 13-18). Peptide (23-110) contains all the residues
      necessary for catalysis. The complexes between all mutants peptides (1-22) with
      (23-110) are all only 10% active, however. The noncovalent complex is
      destabilized less by mutations in the helix than is the intact protein. Double
      mutant cycle and other analyses show, however, that the intrahelical interactions
      are as strong in the noncovalent complex as in the intact protein and so the
      interactions between the helix and the rest of the protein must be weakened on
      cleavage of the 22-23 bond. This could well lead to effects on
      catalysis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7827096
TI  - NMR evaluation of changes in myocardial high energy metabolism produced by
      repeated short periods of ischemia.
AB  - Following our previous results which demonstrated that repeated short periods (2
      min) of ischemia are capable of protecting the isolated rat heart from a
      subsequent global ischemia (30 min), in the present study we have concentrated on
      the metabolic changes occurring in rat hearts during six 2 min ischemia/3 min
      reperfusion cycles. Cardiac high-energy phosphates were monitored using 31P-NMR.
      Phosphocreatine levels fell (50-60%) during each ischemic period, and recovered
      to 70-80% of their initial values during reperfusion. P(i) rose by 59% during the
      first ischemic period, but increased less during subsequent ischemias (30% during
      the 6th occlusion, P < 0.05 vs. the first ischemic period) returning to baseline
      levels after each reperfusion. [ATP], pH, and [Mg2+] remained almost unaffected,
      but there was a decrease in HPLC-determined effluent ATP catabolites. The first
      occlusion led to a 95% drop in contractile function (P < 0.001 vs. baseline), but
      this recovered to 73% upon reperfusion (P < 0.02 vs. baseline), and was 65% at
      the end of the protocol. Phosphorylation potential (PP = [ATP]/([ADP].[P(i)])
      correlated exponentially with total purine (r = 0.90) and with adenosine +
      inosine release (r = 0.81), and by the 6th ischemia/reperfusion cycle, exceeded
      that observed in controls by 21% (P < 0.05). We conclude that repeated short
      periods of ischemia do not lead to any significant alteration in the absolute
      myocardial ATP, but are associated with an enhanced cytosolic energy state in the
      heart, that enables the myocardium to reach a steady albeit lower functional
      state. Adenosine (+inosine) release may be involved in the regulation of the
      energy supply-demand balance.

PMID- 7827097
TI  - Multinuclear magnetic resonance studies of boar seminal plasma.
AB  - Multinuclear magnetic resonance studies were performed on aqueous solutions of
      lyophilisates of boar seminal plasma. 1H- and 13C-NMR spectral assignments were
      obtained by one- and two-dimensional experiments. Four prominent constituents
      were identified in the lyophilisate as well as in the original seminal plasma:
      inositol (95% myo-inositol, 5% scyllo-inositol), citrate, lactate and
      glycerophosphorylcholine (GPC). The concentrations of these compounds were
      evaluated from appropriate 1H- and 13C-NMR resonances using biochemically
      determined citrate as reference. 31P-NMR spectroscopy confirmed the presence of
      GPC and revealed phosphorylcholine, glycerophosphorylserine and
      glycerophosphorylethanolamine as further components.

PMID- 7827098
TI  - Fusinite as a specific probe for the determination of molecular oxygen
      concentration in cells.
AB  - The feasibility of using EPR and the paramagnetic derivative of coal 'fusinite'
      to measure intracellular oxygen concentration in cultured cells in which this
      substance was internalized in the cytoplasm was examined. First, the possible
      cytotoxic effects of fusinite on cultured cells were ruled out by both
      morphological as well as by growth characteristics analyses. After construction
      of a calibration curve in which the EPR spectral linewidth of this substance was
      measured in response to known oxygen concentrations, the efficacy of using
      fusinite in the determination of intracellular oxygen concentration in cells was
      also tested by flowing different known oxygen gas mixtures outside cultured
      cells. The results indicate that fusinite is able of measuring the variations in
      cytoplasmic oxygen concentration that exist in response to the different gas
      mixtures. In addition, as an example of a possible use of fusinite, data are also
      presented demonstrating a decrease in cytoplasmic oxygen concentration during
      respiration in cells with a limited supply of oxygen. In fact, as the oxygen is
      consumed by the cells, the linewidth of fusinite narrows giving an intracellular
      oxygen concentration corresponding to zero. From the results obtained, fusinite
      appears to represent a new extremely precise biophysical cellular oxygen probe
      which may prove useful in the understanding of the complex interrelationships
      between oxygen and normal cell physiology and/or pathology.

PMID- 7827099
TI  - In vitro determination of creatine kinase substrate fluxes using 31P-nuclear
      magnetic resonance.
AB  - Forward (kf) and reverse (kr) rate constants and the corresponding flux rates of
      the creatine kinase catalysed reaction between creatine phosphate (CrP) and
      adenosine triphosphate (ATP); CrP + ADP<-->kf kr ATP + Cr were measured in vitro
      at 295 K. Both rate constants were determined using magnetic resonance saturation
      transfer techniques. To study the dependence of kr and kf on the creatine kinase
      concentration, the creatine kinase activity was varied from 2400 to 75 U.ml-1. At
      equilibrium and high creatine kinase activities, the forward to reverse flux rate
      ratios are close to 1. A dispersion in the reaction rate constants was observed
      at activities < or = 600 U.ml-1. We measured kr > kf for all enzyme activities
      below 600 U.ml-1. This observation could partially be explained by the presence
      of ATPase contamination in the enzyme. These findings are relevant for the in
      vivo studies of creatine kinase activity in the presence of multi-site phosphate
      exchange in cellular ATP-pools. As mitochondrial creatine kinase is not in
      equilibrium these results are also of interest in this area.

PMID- 7827100
TI  - A sheep hydatid cyst glycoprotein as receptors for three toxic lectins, as well
      as Abrus precatorius and Ricinus communis agglutinins.
AB  - The binding properties of a glycoprotein with blood group P1 specificity isolated
      from sheep hydatid cyst fluid with Gal and GalNAc specific lectins was
      investigated by quantitative precipitin and precipitin inhibition assays. The
      glycoprotein completely precipitated Ricinus communis agglutinin (RCA1), Abrus
      precatorius agglutinin (APA) and Mistletoe toxic lectin-I (ML-I). Only 1.0
      microgram of P1 glycoprotein was required to precipitate 50% of 5.1 micrograms ML
      I nitrogen. It also reacted well with abrin-a and ricin, precipitating over 73%
      of the lectin nitrogen added, but poorly or weakly with Dolichos biflorus (DBL),
      Vicia villosa (VVL, a mixture of A4, A2B2 and B4), VVL-B4, Arachis hypogaea
      (PNA), Maclura pomifera (MPL), Bauchinia purpurea alba (BPL) and Wistaria
      floribunda (WFL) lectins. When an inhibition assay in the range of 5.1 micrograms
      N to 5.9 micrograms N of lectins (ML-I, abrin-a; ricin, RCA1, and APA, and 10
      micrograms P1 active glycoprotein interaction was performed; from 76 to 100% of
      the precipitations were inhibited by 0.44 and 0.52 mumol of Gal alpha 1-->4Gal
      and Gal beta 1-->4GlcNAc, respectively, but not or insignificantly with 1.72
      mumol of GlcNAc. The Gal alpha 1-->4Gal disaccharide found in this P1 active
      glycoprotein is a frequently occurring sequence of many glycosphingolipids
      located at the surface of mammalian cell membranes, especially human erythrocytes
      and intestinal cells for ligand binding and microbial toxin attachment. The
      present finding suggests that the Gal alpha 1-->4Gal beta 1-->4GlcNAc sequence in
      this P1 active glycoprotein is one of the best glycoprotein receptors for three
      toxic lectins (ricin, abrin-a, and ML-I) as well as for APA, and RCA1, and the
      result of inhibition assay implies that these lectins are recognizing part or all
      of the Gal alpha 1-->4Gal beta 1-->4GlcNAc sequence in the P1 active
      glycoprotein.

PMID- 7827101
TI  - Kinetic studies on rat liver low M(r) phosphotyrosine protein phosphatases. The
      activation mechanism of the isoenzyme AcP2 by cGMP.
AB  - The reaction mechanisms of p-nitrophenyl phosphate hydrolysis catalyzed by two
      rat liver isoenzymes of the low M(r) phosphotyrosine protein phosphatase (AcP1
      and AcP2) were compared. Furthermore, the effect of some heterocyclic compounds
      on their activities were tested. Cyclic GMP and guanosine causes a particularly
      high activation of the isoenzyme AcP2, whereas its effect on AcP1 is very poor. A
      study on the mechanism of cyclic GMP activation was carried out. The results
      suggest that cyclic GMP activates the AcP2 isoenzyme by increasing the rate of
      the step that leads to the hydrolysis of the covalent enzyme-substrate
      phosphorylated complex formed during the catalytic process. The physiological
      significance of cyclic GMP activation of only one of the two isoenzymes (AcP2)
      remains uncertain.

PMID- 7827102
TI  - Lentil root protoplasts: a transient expression system suitable for
      coelectroporation of monoclonal antibodies and plasmid molecules.
AB  - Protoplasts were isolated from lentil (Lens culinaris) roots and their
      suitability as a transient expression system was investigated. After transfecting
      the protoplasts with the beta-glucuronidase (GUS) gene by either electroporation
      or polyethylene glycol (PEG), the specific activity of the reporter enzyme and
      the cell viability were determined. Electroporation was more effective than PEG
      treatment as transfection procedure and its efficiency was affected by the
      plasmid length. The feasibility of electro-transferring at the same time
      (coelectroporation) inhibitory anti-lipoxygenase monoclonal antibodies and the
      GUS-carrying plasmid pBI 221 was investigated as well. The amount of transferred
      immunoglobulins was quantitated by ELISA and the inhibitory ability of monoclonal
      antibodies on the intracellular target enzyme was determined. Evidence is
      presented for the successful coelectroporation of immunoglobulins and plasmid DNA
      into lentil protoplasts, the two types of macromolecules acting independently of
      each other in the recipient cells.

PMID- 7827103
TI  - Comparative kinetic study of lipases A and B from Candida rugosa in the
      hydrolysis of lipid p-nitrophenyl esters in mixed micelles with Triton X-100.
AB  - (1) Lipases A and B from Candida rugosa catalyzing the hydrolysis of esters in
      micellar media have been characterized kinetically by studies on substrate
      specificity, rate equation forms and modeling of enzyme mechanisms. (2) The study
      on specificity revealed that both lipases are non-specific esterases with similar
      activity against lipid p-nitrophenyl esters micellized with Triton X-100. The
      slight difference was that lipase A has its maximum activity centered in the
      caprylate while that of lipase B is in the laurate. (3) Kinetic studies for both
      lipases were carried out with p-nitrophenyl laurate under three experimental
      conditions: (I) the molar fraction of substrate is fixed and the bulk
      concentration of substrate and Triton X-100 are varied; (II) the bulk
      concentration of substrate is held constant and the molar fraction of substrate
      and bulk concentration of Triton X-100 are varied; and (III) the bulk
      concentration of Triton X-100 is held constant but the bulk concentration of
      substrate and molar fraction of substrate are varied. (4) In case I, a similar
      Michaelis-Menten behaviour was observed with both lipases; the curve fitting gave
      kappcat/Kappm values of 3.0.10(5) and 5.6.10(5) s-1 M-1 for lipases A and B
      respectively. In case II, for both lipases the relationship between rate and the
      molar fraction of substrate required a fitting equation of 2:2 degree polynomial
      quotient. In case III, both lipases showed non-Michaelian behaviour with concave
      up curves in the Eadie-Hofstee plot, a minimum degree of 2:2 in substrate
      concentration being detected for the rate equation. (5) The above results are
      interpreted in terms of the hypothesis that the mechanism of both lipases must
      include at least two different inputs for the molecule of substrate which would
      explain the quadratic terms observed in the rate equation.

PMID- 7827104
TI  - Isolation and characterization of sheep lactoferrin, an inhibitor of platelet
      aggregation and comparison with human lactoferrin.
AB  - Highly purified sheep lactoferrin was isolated from ovine whey in a single
      chromatographic step (FPLC): it was characterized by electrophoresis, N-terminal
      sequence determination and compared with lactoferrins from other species. Sheep
      and human lactoferrins inhibited thrombin-induced platelet aggregation (median
      inhibitory concentration: IC50 5 and 4 microM, respectively). Pepsin hydrolysates
      of human and sheep lactoferrins were fractionated by reverse-phase high
      performance liquid chromatography and only one peak was an inhibitor of platelet
      aggregation. The sheep or human lactoferrin binding to platelets was studied.

PMID- 7827105
TI  - Association of canalicular membrane enzymes with bile acid micelles and lipid
      aggregates in human and rat bile.
AB  - This study was undertaken to gain insights into the characteristics of the
      polymolecular association between canalicular membrane enzymes, bile acids,
      cholesterol and phospholipids in bile and into the celular mechanisms whereby the
      enzymes are secreted into bile. With this purpose, we studied the distribution of
      bile acids, cholesterol, phospholipids, proteins and representative canalicular
      membrane enzymes (alkaline phosphatase, 5'-nucleotidase and gamma-glutamyl
      transpeptidase), which can be considered specific marker constituents, in bile
      fractions enriched in phospholipid-cholesterol lamellar structures (multilamellar
      and unilamellar vesicles) and bile acid-mixed micelles. These fractions were
      isolated by ultracentrifugation from human hepatic bile, normal rat bile and bile
      of rats treated with diosgenin, a steroid that induces a marked increase in
      biliary cholesterol secretion, and were characterized by density, lipid
      composition and transmission electron microscopy. These studies demonstrate that
      alkaline phosphatase, 5'-nucleotidase and gamma-glutamyl transpeptidase are
      secreted into both human and rat bile where they are preferentially associated
      with bile acid-mixed micelles, suggesting a role for bile acids in both release
      of these enzymes and lipids from the canalicular membrane and solubilization in
      bile. In addition, heterogeneous association of these enzymes with nonmicellar,
      lamellar structures in human and rat bile is consistent with the hypothesis that
      processes independent of the detergent effects of bile acids might also result in
      the release of specific intrinsic membrane proteins into bile.

PMID- 7827106
TI  - Glutamine transport and enzymatic activities involved in glutaminolysis in human
      platelets.
AB  - Glutamine is actively metabolized in human platelets, representing a preferential
      mitochondrial oxidative substrate in these cells. The primary importance of this
      metabolic route of glutamine is further confirmed here by the observation that
      platelet glutaminase activity is entirely represented by the phosphate dependent
      glutaminase or glutaminase I, most probably localized in the mitochondrial
      platelet fraction and classified by kinetic analysis as a kidney-type form. The
      following step of the glutamine metabolizing pathway, allowing the entrance of
      the amino acid skeleton carbons in the Krebs cycle, might be catalyzed by both
      glutamate dehydrogenase and aspartate transaminase, the first being entirely
      mitochondrial and the latter 65% mitochondrial. We also investigated platelets
      for the presence of one or more specific transport systems involved in glutamine
      uptake and we present the first evidence for two glutamine transport systems in
      human platelets that by inhibition analysis appear to share characteristics with
      the Na(+)-dependent ASC system and the Na(+)-independent L system for dipolar
      amino acid uptake. Both systems display affinity characteristics for glutamine in
      the range of plasma glutamine concentration and may thus have physiological
      relevance for the uptake of the amino acid in these cells.

PMID- 7827107
TI  - Qualitative and quantitative studies of heparin and chondroitin sulfates in
      normal human plasma.
AB  - Heparin was extracted and purified from normal human plasma, and full
      characterization of its structure and physico-chemical properties was achieved
      for the first time. Plasma was submitted to exhaustive proteolytic treatment with
      papain, trypsin, chymotrypsin, collagenase and pepsin, anion-exchange
      chromatography and precipitation with organic solvents. By this procedure, we
      recovered heparin (about 0.7 mg/100 ml of plasma) and chondroitin sulfate (about
      0.1 mg/100 ml of plasma). Chondroitin sulfate has a peak molecular mass of about
      15,630, and it is composed of about 60% nonsulfated disaccharide, 3.5%
      disaccharide 6-monosulfate and about 40% disaccharide 4-monosulfate, with a
      sulfate-to-carboxyl ratio of 0.41. Heparin, identified by agarose-gel
      electrophoresis, is constituted by about 40% slow-moving component and about 60%
      fast-moving species. This glycosaminoglycan had a peak molecular mass of about
      7000, and was identified as 'typical' heparin by its constituent disaccharide
      composition. About 70% of disaccharides were identified as trisulfated
      disaccharide, and about 18% as disulfated disaccharides, 3% as monosulfated
      disaccharides and 10% as nonsulfated disaccharide. Heparin extracted from normal
      human plasma has a high sulfate-to-carboxyl ratio (2.47) and in vitro
      anticoagulant activity of about 70 I.U. A more quantitative and statistical
      analysis performed on 10 ml of plasma obtained from 10 human healthy volunteers
      revealed a heparin level of 0.54 +/- 0.17 mg/100 ml plasma (mean +/- standard
      deviation) with a coefficient of variation of about +/- 32%. These findings
      demonstrate for the first time the presence of heparin molecules in normal human
      plasma and confirm the importance of adequate extraction processes to purify a
      molecule that strongly interacts with plasma protein components. This is
      discussed in light of other authors that described a polysaccharide molecule
      named heparan sulfate in human plasma.

PMID- 7827108
TI  - Effects of partial hepatectomy, phenobarbital and 3-methylcholanthrene on kinetic
      parameters of glucose-6-phosphate and phosphogluconate dehydrogenase in situ in
      periportal, intermediate and pericentral zones of rat liver lobules.
AB  - Glucose-6-phosphate dehydrogenase (G6PDH) and phosphogluconate dehydrogenase
      (PGDH) are heterogeneously distributed in liver lobules of female rats. The
      maximum activity of both enzymes is approximately twice higher in intermediate
      and pericentral zones than in periportal zones. Enzyme activities and their
      distribution patterns were manipulated by partial hepatectomy and treatment with
      phenobarbital (PB) or 3-methylcholanthrene (3-MC). Vmax values of G6PDH for
      glucose-6-phosphate decreased mainly in intermediate and pericentral zones after
      partial hepatectomy, whereas they increased after PB treatment. Vmax values of
      PGDH for phosphogluconate decreased after partial hepatectomy in both zones,
      whereas other treatments did not have any effect. The affinity of G6PDH for
      glucose-6-phosphate was similar in all zones and it was decreased 2-3 fold by PB
      and 3-MC treatment. The affinity of PGDH for phosphogluconate was 1.4-2.3 times
      lower in intermediate and pericentral zones than in periportal zones of all
      livers tested and was not affected by treatment. From these data it can be
      concluded that not only the maximum activity of enzymes may differ in periportal,
      intermediate and pericentral zones of the liver lobule but also the affinity of
      enzymes for their substrates. The implication of these findings is that metabolic
      flux rates as they occur in vivo in these different metabolic compartments may be
      significantly different from predictions on the basis of maximum enzyme
      activities as detected immunohistochemically, microchemically or
      cytophotometrically.

PMID- 7827109
TI  - Formation of pivaloylcarnitine in heart and brown adipose tissue in the rat.
AB  - Both pivaloylesterified antibiotics and pivalic acid cause pivaloylcarnitine
      excretion into urine in the rat and human. In the present study, the formation of
      pivaloylcarnitine, expressed as short-chain acylcarnitines has been observed in
      rats. The carnitine pool of the rats was radiolabeled by injection of L
      [3H]butyrobetaine 24 h prior to exposure to pivalic acid injected i.p. or
      pivampicillin administered orally. The presence of pivaloylcarnitine in liver,
      heart, kidney, stomach, small intestine, testis, muscle, brown fat, white fat and
      serum was determined at zero time, 0.5, 2, 8 and 24 h after exposure to pivalic
      acid. After injection of pivalic acid, pivaloylcarnitine calculated as percent of
      free carnitine and short-chain acylcarnitines amounted to (mean +/- SD) 1.1 +/-
      0, 15.4 +/- 2.5, 33.4 +/- 0.7 and 37.5 +/- 1.5% in the heart and 1.2 +/- 0.2,
      20.6 +/- 9.5, 29.8 +/- 7.6 and 22.5 +/- 1.6% in brown fat after 0, 0.5, 2 and 8
      h, respectively. 2 h after administration, pivaloylcarnitine calculated as
      percent of free carnitine and short-chain acylcarnitines was highest in the heart
      (20.9 +/- 7.6%) and brown fat (19.0 +/- 8.5%) in the pivalic acid-treated rat,
      and highest in the kidney (12.4 +/- 3.1%) and brown fat (10.2 +/- 2.8%) in the
      pivampicillin-treated rat. Pivaloylcarnitine percent in the liver was 2.8 +/- 0.6
      in the pivalic acid-treated rat, 3.5 +/- 1.2 in the pivampicillin-treated rat and
      1.3 +/- 0.4 in the control group. Pivaloylcarnitine concentration, nmol/g and
      nmol/organ, was highest in the heart and brown fat in both treatment groups. The
      present study suggests that the heart and the brown fat, but not the liver, play
      important roles in pivaloylcarnitine formation in the rat.

PMID- 7827110
TI  - Spectroscopic features of native and bleached opio-melanins.
AB  - Opioid peptides can be converted by tyrosinase into melanin-like compounds, in
      which the peptide moiety is retained. Such pigments, named opio-melanins, exhibit
      a characteristic absorption spectrum with a maximum at about 330 nm and a
      different solubility behaviour with respect to dopa-melanin, being completely
      soluble in hydrophylic solvents at neutral and basic pH. Opio-melanins
      precipitate in aqueous solutions below pH 5.0, and show apparent pKa values of
      3.1, 3.6 and 4.4 for Tyr-Gly-melanin, Tyr-Gly-Gly-melanin and leuenk-melanin,
      respectively. The concomitant oxidation of dopa and opioid peptides by tyrosinase
      produces mixed polymers, showing the distinctive absorption peak at 330 nm. In
      the dark, in the pH range 5.5-7.0 the pigments are completely stable, whereas
      H2O2 addition provokes a slight degradation. At higher pH values or under
      simulated solar illumination with or without hydrogen peroxide, bleaching occurs
      more rapidly than in dopa-melanin. Upon photoirradiation the absorption spectrum
      of opio-melanins undergoes a marked variation, the peak at 330 nm being replaced
      by a broad shoulder in the range 280-350 nm. The absorption spectra of native and
      bleached pigments and the extent of opio-melanins degradation by bleaching
      agents, confirm the hypothesis that the different initial structure of the
      precursors accounts for a final diverse polymeric architecture of these pigments
      with respect to dopa-melanin.

PMID- 7827111
TI  - Conversion of adenosine(5') oligophospho(5') adenosines into inosine(5')
      oligophospho(5') inosines by non-specific adenylate deaminase from the snail
      Helix pomatia.
AB  - Until now, the catabolism of adenosine(5')triphospho(5')adenosine (Ap3A) and
      adenosine(5')tetraphospho(5')adenosine (Ap4A) has been thought to commence with
      either hydrolytic or phosphorolytic cleavage of their oligophosphate chains,
      depending on the organism. Here, we show that in the extracts from the retractile
      'foot' of the snail Helix pomatia deamination predominates; the adenosine
      moieties of these and other adenosine(5')oligophospho(5')adenosines (ApnAs)
      undergo successive deamination leading, via an
      inosine(5')oligophospho(5')adenosine (IpnA), to the corresponding
      inosine(5')oligophospho(5')inosine (IpnI). The reactions are catalyzed by the non
      specific adenylate deaminase described earlier (Stankiewicz, A.J. (1983) Biochem.
      J. 215, 39-44). We describe TLC and HPLC systems which allow the separation of
      any of the deaminated derivatives from its parent compound; Ap2A, Ap3A, Ap4A or
      Ap5A. The Km values for these substrates are 20, 22, 32 and 39 microM,
      respectively, whereas the Km for 5'-AMP is 12 microM. Relative substrate
      specificities for these compounds amount to 25, 18, 14, 7 and 100. The enzyme was
      shown also to deaminate phosphonate and thiophosphate analogues of Ap3A.

PMID- 7827112
TI  - Effects and molecular action of ribosome-inactivating proteins on ribosomes from
      Streptomyces lividans.
AB  - The effects of 29 type 1 and 2 type 2 ribosome-inactivating proteins (RIPs) from
      plants on polyuridylic acid-directed polyphenylalanine synthesis carried out by
      purified ribosomes from Streptomyces lividans were studied. Only dianthin 32,
      saporins R1 and R3, momordin I, trichokirin, Hura crepitans RIP 5 from latex,
      crotins 2 and 3, and PAPs C, R, and S, inhibited polyphenylalanine synthesis.
      Both the type 2 RIPs ricin and volkensin were ineffective on translation. The
      magnesium concentration affected the inhibition of translation to a considerable
      extent. Upon treatment with inhibitory RIPs, extraction of rRNA and further
      treatment with acid aniline, S. lividans ribosomes released an RNA fragment of
      about 130 nucleotides. The 5' terminal sequence of this rRNA fragment was 5'
      GAGGACCGGGACGGACGAACCUCUGGUGUGCCAGUUGU-3', similar to the sequence obtained in
      Escherichia coli. This indicates that the most probable molecular action of these
      RIPs on S. lividans and E. coli ribosomes is the same: depurination of the rRNA
      at a site relevant to the translation mechanism and that has been highly
      conserved throughout evolution.

PMID- 7827113
TI  - Characterization of a new class of inhibitors of the recombinant human liver UDP
      glucuronosyltransferase, UGT1*6.
AB  - The inhibitory effect of a series of novel structurally related compounds on the
      human UDP-glucuronosyltransferase UGT1*6 stably expressed in a V79 cell line was
      investigated. The inhibitors contain a lipophilic N-acyl phenylaminoalcohol
      residue and a uridine moiety connected by a spacer varying for each compound. The
      effects of these compounds on the glucuronidation reaction measured with 4
      methylumbelliferone as substrate were determined. The best inhibitor of the
      series, D-DPMSU, had an IC50 of 39 microM in the assay conditions. Low Ki values
      were found toward both UDP-glucuronic acid and 4-methylumbelliferone (17 and 21
      microM, respectively). The inhibition was competitive toward both substrates. A
      similar strong and competitive inhibitory effect was observed with two other
      inhibitors, DHPASU and DHPASiU. Another compound, D-DPASiU, showed a pure
      competitive inhibition towards UDP-glucuronic acid, but a non-competitive
      inhibition towards the acceptor substrate. These data and the optimization of the
      structures of the inhibitors by molecular modeling suggest that D-DPMSU and
      DHPASiU compounds may be transition state analog inhibitors of the recombinant
      UGT1*6 enzyme.

PMID- 7827114
TI  - Purification and characterization of a non-hemorrhagic metalloprotease from
      Agkistrodon halys brevicaudus venom.
AB  - A non-hemorrhagic metalloprotease (protease L4) was purified from the venom of
      Chinese Mamushi (Agkistrodon halys brevicaudus) by gel filtration and anion
      exchange chromatography. Protease L4 has the molecular weight of 22,000 and its
      optimum pH was 8.5. The protein was stable in the pH range of 5-9 and below 40
      degrees C. The proteolytic activity was inhibited by metal-chelating agents and
      some metal ions. Calcium ion activated the activity dose-dependently, but had
      only a minor effect on the thermal and pH stability. L4 showed fibrinogenase
      activity, hydrolyzing only the A alpha chain of fibrinogen. The protease cleaved
      preferentially at the N-terminal of Leu and His residues of some peptides.

PMID- 7827115
TI  - Modulation of substrate selectivity in plasma lipid transfer protein reaction
      over structural variation of lipid particle.
AB  - The modulation of substrate selectivity of human plasma LTP reaction is the
      subject of the present investigation. The moderate selectivity by a factor of 5
      to 6 was observed in the LTP-catalyzed transfer of cholesteryl ester over
      triacylglycerol between plasma lipoproteins. On the other hand, the transfer of
      cholesteryl ester by LTP was highly selective over the negligible transfer of
      triacylglycerol, by a factor of 60 to 500, between the microemulsions with LDL
      size, regardless of the activators such as human and pig apolipoprotein (apo) A
      I, human apo C-III and apo E that bound to the surface of the emulsion in
      equilibrium. The presence of free cholesterol in these microemulsions reduced
      slightly the rate of cholesteryl ester transfer but had no effect on
      triacylglycerol transfer. Other surface-active reagents such as cholic acid,
      Triton X-100 and Tween-20, did not have an effect on the triacylglycerol transfer
      either. Triacylglycerol transfer by LTP became measurable between such lipid
      particles as prepared by co-sonication of lipid with pig apo A-I and isolated as
      the mixed-microemulsions in the density of LDL and HDL. In these conditions, the
      substrate selectivity for cholesteryl ester over triacylglycerol was a factor of
      6 to 16 mimicking the ratio in plasma lipoproteins. The conformation of pig apo A
      I estimated by circular dichroism showed that its apparent helical content was
      further more induced when apo A-I was integrated into the mixed-microemulsion by
      co-sonication than the lipid-bound apo A-I in equilibrium. Apo A-I, thus
      integrated into lipid particles, was highly resistant to the denaturation by
      guanidine hydrochloride while the lipid-bound apo A-I in equilibrium was
      denatured as readily as the lipid-free protein. Thus, triacylglycerol transfer by
      LTP was induced by structural modulation of substrate-carrying lipid particles
      such as higher integration of apolipoproteins.

PMID- 7827116
TI  - Lipoxygenase-catalyzed oxygenation of arachidonylethanolamide, a cannabinoid
      receptor agonist.
AB  - Various purified lipoxygenases were incubated with [14C]arachidonylethanolamide
      which is an endogenous ligand for cannabinoid receptors. When radioactive
      products were analyzed by thin-layer chromatography, porcine leukocyte 12
      lipoxygenase and rabbit reticulocyte and soybean 15-lipoxygenases produced polar
      compounds at about the same reaction rates as that of oxygenation of free
      arachidonic acid. In contrast, the reaction of human platelet 12-lipoxygenase
      proceeded at a much lower rate, and porcine leukocyte 5-lipoxygenase was totally
      inactive. The result indicated that the lipoxygenases, which had been shown
      previously to be capable of oxygenating esterified polyunsaturated fatty acids,
      were also active with the arachidonylethanolamide. High-performance liquid
      chromatography, ultraviolet and mass spectrometry and nuclear magnetic resonance
      spectroscopy identified the major product by leukocyte 12-lipoxygenase as 12
      hydroperoxy-5,8,10,14-eicosatetraenoylethanolamide and that by 15-lipoxygenases
      as 15-hydroperoxy-5,8,11,13-eicosatetraenoylethanolamide. The 15-hydroxy
      derivative inhibited electrically-evoked contraction of mouse vas deferens with
      an IC50 of 0.63 microM as well as arachidonylethanolamide (0.17 microM), but the
      12-hydroxy derivative was much less effective.

PMID- 7827117
TI  - Fluorescence properties of oxidised human plasma low-density lipoproteins.
AB  - Appearance of fluorescence emission between 380-550 nm (lambda exc 350-400 nm) in
      freshly prepared low-density lipoprotein from asymptomatic normolipemic human
      plasma revealed the presence of in vivo oxidative modification of its protein
      moiety. Low-density lipoprotein elicited seven fluorophores in three dimensional
      fluorescence spectrogram. Assignment of fluorescent chemical structures
      originating from oxidative modification of the protein moiety of low-density
      lipoprotein has been made with the help of second derivative fluorescence
      spectroscopy.

PMID- 7827118
TI  - Effect of transforming growth factor-beta on lipoprotein lipase in rat
      mesenchymal heart cell cultures.
AB  - The effect of recombinant transforming growth factor-beta 2 (rTGF-beta 2) on
      lipoprotein lipase (LPL) synthesis was studied in mesenchymal rat heart cell
      cultures. Addition of rTGF-beta 2 to culture medium containing 20% serum resulted
      in a time-dependent decrease in LPL activity. With 10 ng/ml a 30% fall occurred
      after 12 h and only 20% of enzyme activity remained after 24 h with 5 or 10
      ng/ml. The minimal effective dose of rTGF-beta 2 was 0.1 ng/ml and a 20% decrease
      occurred after exposure for 24 h. Antibodies specific to TGF-beta 2 blocked this
      effect. The decrease in enzymic activity was accompanied by a decrease in enzyme
      mass and LPL mRNA. Addition of rTGF-beta 2 was effective only during the first
      week in culture, when enzyme activity was increasing but not after 12 days when
      the cultures were overconfluent, and the enzyme activity was high.

PMID- 7827119
TI  - Distribution and metabolism of arachidonic and docosahexaenoic acids in rat
      pineal cells. Effect of norepinephrine.
AB  - The time-course incorporation of 10 microM [14C]arachidonic (AA) and
      docosahexaenoic (DHA) acids into glycerolipids was studied in rat pineal cells.
      The incorporation of both labeled fatty acids into total lipids was approximately
      equal, but their distribution profiles among the various cell lipids showed
      marked differences. The esterification of [14C]DHA in the neutral lipids,
      triacylglycerols (TAG) and cholesterol esters (CE), was 2-fold higher than that
      of [14C]AA whereas the opposite could be observed in total phospholipids (PL).
      The order of incorporation into PL was phosphatidylcholine (PC) >
      phosphatidylinositol (PI) = phosphatidylethanolamine (PE) for [14C]AA and PC = PE
      for [14C]DHA, the incorporation of both fatty acids being not detected in
      phosphatidylserine (PS) and that of DHA not in PI. When using 0.5 microM [3H]
      fatty acids, the respective distribution patterns resembled that of fatty acids
      at 10 microM, except for a lower proportion in TAG. The stimulation of 3H-labeled
      cells by 100 microM norepinephrine induced a 170% increase of basal release of
      [3H]AA into the medium, while [3H]DHA was virtually not released. However, the
      analysis of cell labeling revealed that both [3H] fatty acid levels were
      decreased in PL and increased in TAG. These findings suggest different
      involvement for AA and DHA in the pineal function. The preferential incorporation
      of DHA in TAG suggests that TAG might play an important role in the pineal
      enrichment with DHA. The absence of DHA release after NE stimulation, which
      however cannot be ascertained, may raise the question of the role of DHA in NE
      transduction.

PMID- 7827120
TI  - Two new phospholipids, hydroxyarchaetidylglycerol and
      hydroxyarchaetidylethanolamine, from the Archaea Methanosarcina barkeri.
AB  - The structures of two new ether phospholipids of the methanogenic Archaea,
      Methanosarcina barkeri, were determined as hydroxyarchaetidylglycerol and
      hydroxyarchaetidylethanolamine by means of chemical, chromatographic and
      enzymatic analyses, and fast atom bombardment-mass spectrometry. These lipids are
      hydroxy diether analogs of phosphatidylglycerol and phosphatidylethanolamine,
      respectively, with beta-hydroxyarachaeol (2-O-(3'-hydroxy)phytanyl-3-O-phytanyl
      sn-glycerol) as a core lipid. In addition, two other ether phospholipids, usual
      archaetidylglycerol and archaetidylethanolamine, were also identified in the
      organism. The stereochemical structure of the unalkylated glycerophosphate of
      hydroxyarchaetidylglycerol and archaetidylglycerol was determined as sn-glycerol
      3-phosphate by use of sn-glycerol-3-phosphate dehydrogenase. The stereochemical
      configuration of the glycerophosphoglycerol backbone of these lipids was a mirror
      image of that of diacylphosphatidylglycerol from the organisms of the domains
      Bacteria and Eucarya, and it was shared with extremely halophilic Archaea. These
      four phospholipids, in addition to five lipids that had already been reported,
      accounted for 88% of the total polar lipids of this organism.

PMID- 7827121
TI  - Subcellular distribution of N-ethylmaleimide-sensitive and -insensitive
      phosphatidic acid phosphohydrolase in rat brain.
AB  - The dephosphorylation of phosphatidic acid by phosphatidic acid phosphohydrolase
      (PAP) is important in both cell-signalling and in glycerolipid metabolism.
      However, these roles are apparently performed by two different enzymes, which can
      be distinguished by their sensitivity in vitro to N-ethylmaleimide (NEM). Both of
      these enzymes are present in rat brain as well as a wide range of other rat
      tissues. However, the quantity and specific activity of each enzyme varies
      considerably between different tissues, as does the ratio of the two enzymes in
      each tissue. Tissues rich in glycerolipids are abundant in NEM-sensitive PAP,
      whereas there is no obvious pattern to the distribution of the NEM-insensitive
      enzyme in the different tissues tested. Studies on brain cortex, which is
      relatively rich in both forms of PAP, indicate that the NEM-insensitive PAP is
      located in the synaptosomes, and the NEM-sensitive enzyme present in the cytosol
      and microsomes. The NEM-sensitive PAP can also be translocated from the cytosol
      to the microsomes by oleate. When assayed against a range of phosphatidic acids,
      NEM-sensitive PAP showed a preference for phosphatidic acids with short acyl
      chains and for those containing arachidonate, whereas NEM-insensitive PAP had a
      preference for short and unsaturated acyl chains. The two isozymes also had
      different activity profiles against these substrates suggesting that they are in
      fact different enzymes. The implications for these results on the putative roles
      of the two forms of PAP are discussed.

PMID- 7827122
TI  - Amino acid sequences of three acyl-binding/lipid-transfer proteins from rape
      seedlings.
AB  - The complete amino acid sequence of three acyl-binding/lipid-transfer proteins,
      AB/LTP I, AB/LTP II and AB/LTP III from germinated rape seeds were determined.
      AB/LTP I and AB/LTP II consist of 93 residues and the M(r) was determined as 9408
      by mass spectrometry and calculated as 9406.8 from the sequence. AB/LTP III
      consists of 92 residues and the M(r) was determined as 9424 by mass spectrometry
      and calculated as 9422.8 from the sequence. The primary structures were
      determined by automated Edman degradations of the intact proteins and peptides
      obtained from digestion with trypsin and endoproteinase Asp-N and cyanogen
      bromide cleavage. Use of 252Cf plasma-desorption mass spectrometry facilitated
      the identification and verification of peptides.

PMID- 7827123
TI  - The effect of reduction of lipoprotein (a) on cellular cholesterol synthesis in
      non-diabetic and type 2 diabetic subjects.
AB  - This study investigates the effect of Lipoprotein (a) (Lp(a)) on cellular
      cholesterol synthesis in non-diabetic (n = 7) and Type 2 (non-insulin-dependent)
      diabetic subjects (n = 7) with elevated levels of Lp(a) (> 20 mg/dl). N
      Acetylcysteine was used to lower Lp(a) in the control subjects and their
      lipoproteins were re-examined after 7 days of treatment. Low-density lipoprotein
      (LDL) was isolated and separated from Lp(a) by sequential ultracentrifugation.
      Regulation of cellular cholesterol synthesis was assessed by measuring
      incorporation of [14C]acetate into mononuclear leucocytes in the presence of LDL
      and Lp(a). Cellular cholesterol content was determined by a fluorometric assay.
      Delivery of cholesterol to the cell was examined using [3H]cholesteryl oleate
      labelled LDL or Lp(a). LDL (5 micrograms/ml) from non-diabetic subjects
      suppressed cellular cholesterol synthesis by 66.2%, while Lp(a) at a similar
      concentration only suppressed cholesterol synthesis by 5.8% (P < 0.001). At a
      concentration of 20 micrograms/ml, Lp(a) suppressed cholesterol synthesis by
      31.7%. The situation was similar in the diabetic subjects. Serum LDL cholesterol
      in non-diabetic subjects was 4.2 +/- 0.5 mmol/l and the LDL esterified/free
      cholesterol ratio was 2.6 +/- 0.2. Following treatment with N-acetylcysteine, LDL
      cholesterol did not change, while Lp(a) decreased significantly by 24% (P <
      0.05). The LDL esterified/free cholesterol ratio decreased to 2.2 +/- 0.2 (P <
      0.05) and there was a significant increase in the ability of the subjects LDL to
      inhibit cellular cholesterol synthesis (P < 0.05). There was a significant
      negative correlation between plasma Lp(a) and the ability of the patients' LDL to
      inhibit cellular cholesterol synthesis (r = -0.68, P < 0.01). [3H]Cholesteryl
      oleate-LDL (5 micrograms/ml) delivered 266 +/- 13 ng cholesteryl oleate/mg cell
      protein, while it took 20 micrograms of [3H]cholesteryl oleate-labelled-Lp(a) to
      deliver a similar concentration (315 +/- 21 ng cholesteryl oleate/mg cell
      protein). In conclusion it appears possible that the atherogenicity of Lp(a) may
      be associated with its effect on the LDL receptor which alters LDL receptor
      uptake, LDL composition and cellular cholesterol synthesis.

PMID- 7827124
TI  - Role of N-linked glycosylation of lecithin:cholesterol acyltransferase in
      lipoprotein substrate specificity.
AB  - Lecithin:cholesterol acyltransferase (LCAT) is responsible for the formation of
      cholesteryl ester in plasma. LCAT is a glycoprotein which has a carbohydrate
      content estimated to be approx. 25% of its total mass. Previous studies of
      recombinant LCAT have characterized the function of the four N-linked
      glycosylation sites of LCAT with respect to reconstituted HDL analogue
      substrates. In order to investigate the relationship between N-linked
      glycosylation and the ability of LCAT to esterify cholesterol in native plasma
      lipoproteins, we have expressed a series of mutant LCAT cDNAs in which each of
      the four glycosylation consensus sequences was eliminated individually. All
      mutant LCAT proteins were secreted by stably transfected baby hamster kidney
      cells. The ability of mutant LCATs to esterify cholesterol in purified native
      lipoproteins indicated that the elimination of the carbohydrate chain at position
      20 of recombinant LCAT was associated with a lower activity than the wild type
      enzyme when HDL was used as a substrate, but no inhibitory effect was observed
      when LDL was used as a substrate. A mutant enzyme with a substitution of Asn-84-
      >Gln or Asn-272-->Gln displayed a decreased ability to esterify cholesterol in
      either HDL or LDL. In contrast, the loss of a carbohydrate chain at position 384
      was associated with an increase in enzyme activity for both HDL (1.5-fold) and
      LDL (2.5-fold) substrates. Kinetic analysis of these recombinant enzymes
      indicated that the apparent Km values for cholesterol in either HDL or LDL were
      not affected, but that the differences in activities were due to changes in the
      apparent Vmax. Heat inactivation studies were performed to assess the role of
      specific carbohydrate groups in enzyme stability. Loss of a carbohydrate chain at
      position 20, 272 or 384 decreased thermostability of LCAT whereas a mutation at
      position 84 did not affect thermostability. These results suggest that individual
      carbohydrate chains confer specific structural and functional properties to LCAT.

PMID- 7827125
TI  - Metabolism and fate of neutral lipids of fetal lung fibroblast origin.
AB  - Fetal rat lung fibroblasts characteristically increase their triacylglycerol (TG)
      stores during development. Both fibroblasts and alveolar type II (TII) cells can
      synthesize TG de novo, but only fibroblasts can absorb TG from culture medium,
      and retain the TG in a stable state. When fibroblasts pre-labelled with
      [3H]triolein are recombined with TII cells in organotypic culture the radiolabel
      appears in TII cell disaturated phosphatidylcholine (disatPC). When fibroblasts
      are preloaded with increasing amounts of TG there is a commensurate increase in
      TII cell disatPC following organotypic culture. Comparison of [3H]triacylglycerol
      and [14C]glucose incorporation into type II cell phospholipids revealed
      preferential use of TG for the surface-active phospholipids disatPC (10-fold
      greater) and phosphatidylglycerol (23-fold greater). These in vitro data suggest
      that fibroblasts provide lipid substrate for TII cell surfactant phospholipid
      synthesis.

PMID- 7827126
TI  - Renal leukotriene C4 synthase: characterization, partial purification and
      alterations in experimental glomerulonephritis.
AB  - Cysteinyl leukotrienes (LT) play an important role in the development of
      experimental glomerulonephritis (GN). We have partially purified and
      characterized LTC4 synthase, the enzyme responsible for cysteinyl LT formation,
      from rat renal microsomes and have investigated this enzyme activity in nephritic
      rats. LTC4 formation, measured in vitro, was linear for > 10 min at 25 degrees C
      in the presence of 50 mM serine borate (an inhibitor of gamma-glutamyl
      transpeptidase), with Km values for LTA4 and GSH of 56 microM and 8.5 mM,
      respectively. Detergent solubilization and anion-exchange chromatography of
      microsomal proteins resulted in a 7-fold increase in enzyme specific activity.
      Enzymatic and immunoblot analysis demonstrated that cytosolic and microsomal
      glutathione S-transferase (GST) activities were distinct from LTC4 synthase
      activity. Comparison of LTC4 synthase activity in nephritic rats over 21 days
      revealed an initial increase over the first 24 h following injection of
      nephrotoxic sera, followed by a subsequent decline until day 7 and a gradual
      recovery by day 21. Inhibition of LT biosynthesis with MK-0591 (10 mg kg-1 d-1)
      reduced GN-associated proteinuria by 72% (P < 0.05). These results suggest a
      potential mechanism for enhanced cysteinyl LT formation in the development of
      experimental GN and further support their causal role in the etiology of this
      disease.

PMID- 7827127
TI  - Human apo A-I in transgenic mice is more efficient in activating
      lecithin:cholesterol acyltransferase than mouse apo A-I.
AB  - This study shows that, in control and transgenic mice, there is a parallel
      increase in LCAT activity and plasma apo A-I concentrations during postnatal
      development. We also demonstrate that human apo A-I is a much more efficient
      activator (1.6-fold) of mouse LCAT activity than mouse apo A-I. We propose that
      the differences in amino acid sequence between human and mouse apo A-I may
      account for the higher LCAT activity with human apo A-I.

PMID- 7827128
TI  - Primary structure of a lipoxygenase from barley grain as deduced from its cDNA
      sequence.
AB  - A full length cDNA sequence for a barley grain lipoxygenase was obtained. It
      includes a 5' untranslated region of 69 nucleotides, an open reading frame of
      2586 nucleotides encoding a protein of 862 amino acid residues and a 3'
      untranslated region of 142 nucleotides. The molecular mass of the encoded
      polypeptide was calculated to be 96.392. Its amino acid sequence shows a high
      homology with that of other plant lipoxygenases identified to date.

PMID- 7827129
TI  - Beware of connective tissue proteins: assignment and implications of collagen
      absorptions in infrared spectra of human tissues.
AB  - Infrared spectra of human central nervous system tissue and human breast
      carcinoma are presented. The spectra are discussed in terms of the composition of
      the tissues. It is shown that differences between spectra of white and grey
      matter can be rationalised on the basis of differences in lipid content. Spectra
      of the choroid plexus and arachnoid villus of the meninges show a series of
      absorptions not observed in other CNS tissue. These absorptions are discussed in
      terms of the connective tissue content of the samples. We demonstrate that the
      presence of collagen results in the appearance of a series of characteristic
      absorptions which may be mis-assigned as DNA phosphate absorptions. The
      implications of the presence of collagen in tissues for the diagnosis of disease
      states by IR spectroscopic methods, with particular reference to cancer, is
      discussed.

PMID- 7827130
TI  - Relationships between proto-oncogene expression and apoptosis induced by
      anticancer drugs in human prostate tumor cells.
AB  - A variant of human prostate PC3 cells, isolated from PC3 cells, was shown to be
      significantly resistant (> 10-fold) to several clinically active anticancer
      drugs, including VP-16 and cisplatin. Previous studies showed that resistance to
      these drugs was not due to expression of the mdr1 gene, or modifications in
      topoisomerases but may have resulted from high expressions of certain proto
      oncogenes (Yamazaki et al. (1994) Biochim. Biophys. Acta 1226, 89-96). Flow
      cytometry, DNA gel electrophoresis and northern blot analysis were used to
      further characterize drug responses in sensitive and resistant cells. Treatment
      of the sensitive PC3 cells with VP-16 and CDDP resulted in accumulation of cells
      in S and G2, and G1 and S phases, respectively, and caused significant
      degradation of the genomic DNA into internucleosomal sized DNA fragments,
      indicating apoptosis. In contrast, resistant PC3 cells showed little or no DNA
      fragmentation. Resistant PC3(R) cells expressed 2-3-fold more bcl2 protein than
      the parental PC3 cells, and overexpressed c-myc, c-jun and H-ras mRNA compared to
      sensitive cells. Treatment with VP-16 or CDDP significantly induced c-myc mRNA
      levels in sensitive PC3 cells. H-ras message was not affected by either VP-16 or
      CDDP treatment in PC3 cells. These studies, taken together, suggest that a
      differential susceptibility to apoptosis and chemosensitivity may be related to
      altered levels of bcl2 and/or oncogene overexpression in PC3(R) cells.

PMID- 7827131
TI  - Cholesterol efflux from human monocyte-derived macrophages in the presence of LpA
      I:A-II.
AB  - Previous epidemiological studies have suggested that the LpA-I subfraction of HDL
      is more protective than the LpA-I:A-II subfraction against the development of
      cardiovascular disease. A possible basis for a specific anti-atherogenic function
      of LpA-I emerged from studies of cholesterol efflux from cultured mouse
      adipocytes. LpA-I efficiently removed excess cholesterol from the mouse
      adipocytes, while LpA-I:A-II was ineffective. On the other hand, LpA-I:A-II was
      able to stimulate cholesterol efflux from a number of other cell types including
      rodent macrophages. Because of previously reported differences in HDL stimulation
      of cholesterol clearance from macrophages of different origins, we determined
      whether LpA-I:A-II could induce cholesterol efflux from cultured human monocyte
      macrophages. Our findings showed that LpA-I:A-II and HDL3 effectively stimulated
      cholesterol efflux from human monocyte-macrophages enriched with cholesterol by
      incubation with AcLDL. LpA-I:A-II also decreased by one-half the amount of
      cholesterol accumulated when macrophages were incubated with AcLDL and LpA-I:A-II
      together. Thus, it would appear that the differential anti-atherogenic effects of
      LpA-I:A-II and LpA-I do not derive from their effects on macrophage cholesterol
      efflux. Possibly these HDL subfractions differentially affect other biologic
      processes that modulate the development of cardiovascular disease.

PMID- 7827132
TI  - Irreversibly glycated albumin alters the physico-chemical characteristics of low
      density lipoproteins of normal and diabetic subjects.
AB  - In diabetic plasma, glycated albumin and glycated LDL coexist with augmented
      levels of peroxides, conditions frequently associated with the development of
      accelerated atherosclerosis. The direct interaction between irreversibly glycated
      albumin, LDL and oxidation have not been explored yet. We tried to elucidate
      whether irreversibly glycated albumin (AGE-Alb) induces changes in the chemistry
      and morphology of LDL particle, and if AGE-Alb has the ability to scavenge free
      radicals, as reported for native albumin. LDL isolated from normal (nLDL) or
      diabetic human subjects (dLDL) was incubated in vitro with AGE-Alb in conditions
      of autoxidation (37 degrees C, 24-48 h in the absence of oxidation inhibitors) or
      of Cu2+ induced-oxidation. The results showed that, especially in the latter
      condition, AGE-Alb induced marked physico-chemical modifications of both nLDL and
      dLDL without significant changes in the level of peroxides. Incubation with AGE
      Alb decreased the cholesteryl esters/unesterified cholesterol ratio of nLDL by
      30% and of dLDL by approximately 50%. Concomitantly, in oxidative conditions a
      marked increase (approximately 3-fold) in the
      lysophosphatidylcholine/phosphatidylcholine ratio of dLDL was detected.
      Apolipoprotein B integrity as well as the morphology of the lipoprotein particles
      were drastically affected. To a lesser extent, these modifications occurred also
      in the presence of inhibitors of oxidation at 37 degrees C, but not at 4 degrees
      C. The above described effects were constantly more pronounced in the case of
      dLDL. These results indicated that in the absence of other plasma or vascular
      tissue components (e.g., endothelial cells, extracellular matrix) AGE-Alb by
      itself induces alterations in the chemistry and morphology of LDL, especially of
      glycated LDL, modifications that may account for the occurrence of accelerated
      atherogenesis in diabetes.

PMID- 7827133
TI  - The reaction of methylglyoxal with human and bovine lens proteins.
AB  - Methylglyoxal is an endogenous metabolite that increases in diabetes and has been
      implicated in some of its long-term complications such as retinopathy, neuropathy
      and cataract. We investigated the reaction of methylglyoxal with isolated human
      and bovine lens crystallins (alpha, beta H, beta L and gamma). After 7 days
      incubation at 37 degrees C and pH 6.9, the reaction of methylglyoxal with lens
      proteins yielded stable adducts that exhibited fluorescent properties. SDS
      polyacrylamide gel electrophoresis was used to monitor aggregation and
      crosslinking of the modified protein and autoradiography showed that
      [14C]methylglyoxal was incorporated into all the protein bands. Bovine gamma
      crystallin was the most reactive towards methylglyoxal. Reaction of methylglyoxal
      with bovine gamma II-crystallin, which is found mainly in the lens nucleus, could
      alter the change surface network of the molecule, resulting in aggregation,
      increased light scattering and hence cataract. Modification of gamma II
      crystallin by methylglyoxal produced an overall loss of positive charge and an
      increase in molecular weight and non-disulfide covalent crosslinking. Amino acid
      analysis of the modified gamma II-crystallin showed a loss of 47% of arginine
      residues.

PMID- 7827134
TI  - Tay-Sachs disease: intron 7 splice junction mutation in two Portuguese patients.
AB  - A single nucleotide transversion (G-->C) in the 5' donor site of intron 7 of the
      beta-hexosaminidase alpha-chain gene was identified in two Portuguese patients
      with infantile Tay-Sachs disease. One patient was found to be homozygous and the
      other a compound heterozygote with the four-base insertion in exon 11 on the
      other allele. In fibroblasts from the homozygous patient the beta-hexosaminidase
      alpha mRNA was observed as a nearly undetectable fast migrating band. Through
      cDNA-PCR amplification and hybridization with full length alpha cDNA several
      fragments of smaller size than the normal transcript were detected, most of them
      lacking exon 7. We propose that this point mutation in the 5' donor site of
      intron 7 of the beta-hexosaminidase alpha-chain gene is responsible for an
      inefficient and abnormal processing of the mutant transcript, resulting in
      functional abnormality.

PMID- 7827135
TI  - A peroxidative model of human erythrocyte intracellular Ca2+ changes with in vivo
      cell aging: measurement by 19F-NMR spectroscopy.
AB  - Numerous changes occur with human erythrocyte aging in vivo, including an
      increase in free ionic intracellular calcium concentration ([Ca2+]i) (N.R. Aiken
      et al. (1992) Biochim. Biophys. Acta 1136, 155-160). An attractive hypothesis of
      cell aging suggests that oxidative stress is responsible for many age-related
      changes. To determine whether oxidative stress leads to increased intracellular
      Ca2+ concentrations, we used the fluorinated calcium probe 5,5'-difluoroBAPTA and
      fluorine nuclear magnetic resonance spectroscopy (19F-NMR) to measure [Ca2+]i
      following mild hydrogen peroxide (H2O2) stress to young red cells. Cells were
      separated using density centrifugation, exposed to 815 microM H2O2, loaded with
      the calcium probe, and [Ca2+]i measured. Intracellular [Ca2+] increased from 62
      nM (+/- 4, S.E.) in untreated young cells to 173 nM (+/- 11) in peroxide treated
      cohort young cells. This value approached our previously reported [Ca2+]i of 221
      nM (+/- 25) in old human erythrocytes. Pretreatment of young cells with (a)
      cobalt, which blocks Ca2+ influx through calcium channels, or (b) carbon
      monoxide, which prevents methemoglobin formation, inhibited the peroxide-induced
      increase in ionic intracellular calcium. These findings are consistent with the
      hypothesis that oxidative stress of erythrocytes contributes to the increased
      [Ca2+]i found in senescent cells, and that this is due to increased membrane Ca2+
      leak resulting from oxidatively induced methemoglobin-cytoskeletal protein
      crosslinking.

PMID- 7827136
TI  - Copper incorporation into ceruloplasmin in rat livers.
AB  - Ceruloplasmin, a blue copper oxidase found in plasma, is synthesized in
      hepatocytes as a single polypeptide chain consisting of a 19 amino acid leader
      peptide plus 1046 amino acids of mature protein (132 kDa). Holoceruloplasmin is
      secreted into the plasma with 6-7 atoms of copper bound per molecule. In this
      study we identified apo- and holoceruloplasmin and examined the mechanism of
      copper incorporation during ceruloplasmin biosynthesis using the Long-Evans
      Cinnamon (LEC) rat which does not incorporate copper into newly synthesized
      ceruloplasmin. We followed the conversion from ceruloplasmin precursor (with
      little or no carbohydrate) to the larger product (after carbohydrate addition),
      which occurred in the secretory compartments of hepatocytes, by native gel
      electrophoresis. We found that copper accumulates in the hepatocellular Golgi
      apparatus of LEC rats due to a disorder in the process of copper incorporation.
      The data indicate that copper is incorporated into ceruloplasmin late in the
      course of its transport through the secretory compartments.

PMID- 7827137
TI  - Constitutive expression and inducibility of O6-methylguanine-DNA
      methyltransferase and N-methylpurine-DNA glycosylase in rat liver cells
      exhibiting different status of differentiation.
AB  - We have analyzed the expression of the DNA repair genes O6-methylguanine-DNA
      methyltransferase (MGMT) and N-methylpurine-DNA glycosylase (MPG) at RNA and
      protein activity level in primary rat hepatocytes in vitro and various rat
      hepatoma cell lines exhibiting different status of differentiation. The basal
      level of MGMT mRNA and activity correlated well with the degree of
      differentiation, as measured by tyrosine aminotransferase (TAT) mRNA expression.
      Induction of MGMT mRNA and protein activity by X-ray and N-methyl-N'-nitro-N
      nitrosoguanidine (MNNG) treatment was most pronounced in the well-differentiated
      hepatocytes and in various differentiated hepatoma cell lines (up to 6-fold).
      There was virtually no induction in H5 hepatoma cells which exhibited the lowest
      degree of differentiation and expressed only low amounts of MGMT. For the other
      hepatoma cell lines tested, MGMT induction did not clearly correlate with TAT
      expression. Thus, Fao cells which exhibited a high degree of differentiation
      responded only very weakly with respect to induction. The results indicate that
      the basal level of MGMT mRNA expression is dependent on liver-specific regulatory
      factors, whereas the inducibility is a more complex phenomenon not solely
      dependent on them. Contrary to MGMT, MPG was constitutively expressed at
      relatively high amounts in all cell lines tested and no correlation was apparent
      with the degree of differentiation. MPG activity was significantly induced by
      mutagen treatment only in H4IIE cells. The tumor promoter phenobarbital induced
      MGMT, but not MPG mRNA in hepatocytes. The results indicate that MGMT and MPG are
      not co-regulated. Hepatoma cells with low MGMT level were most sensitive to MNNG
      induced cytotoxicity. On the other hand, no correlation was apparent between MPG
      activity and sensitivity of the cell lines to methylating agents indicating that
      the MPG level is not predictive for alkylating drug resistance.

PMID- 7827138
TI  - Change of isoforms' spectra of alpha-L-fucosidase from human skin fibroblasts in
      intracellular storage of nonhydrolyzable substances.
AB  - The effect of exogenous and endogenous products storage in lysosomes on the
      activity and multiple forms of alpha-L-fucosidase from human skin fibroblasts was
      investigated. It was shown that sucrose load, modelling intralysosomal
      accumulation of nonhydrolyzable products, causes certain changes in secretion
      level of alpha-L-fucosidase and multiple forms' spectra of the intracellular and
      secreted enzymes. These changes were different for the enzyme from embryonal and
      postnatal normal fibroblasts. Some changes of secreted alpha-L-fucosidase
      isoforms' spectra were found in fibroblasts from a patient with Fabry's disease,
      characterized by the intralysosomal storage of di- and trihexosylceramides. The
      alterations of isoforms' profiles in Fabry fibroblasts at the early and late
      accumulation stages were similar to those in sucrose-loaded embryonal and
      postnatal fibroblasts, respectively. It is proposed that intralysosomal
      accumulation of nonhydrolyzable compounds influences the alpha-L-fucosidase
      posttranslational processing.

PMID- 7827139
TI  - Copper-induced and photosensitive oxidation of serum low-density lipoprotein. The
      relation to cholesterol level and inter-species differences.
AB  - Hypercholesterolemia is associated with a higher risk for developing
      atherosclerotic coronary heart disease. During the past few years, evidence has
      been increasing that modification of lipoproteins, particularly low-density
      lipoprotein (LDL) oxidation, might be involved in the pathogenesis of
      atherosclerosis. To compare these factors metal-dependent and -independent
      photodynamic methods were used for the screening of several indexes of LDL
      oxidation. Lipid oxidation has been continuously monitored by the increase of
      conjugated dienes and verified by iodometric and thiobarbituric reaction assay. A
      close association between LDL cholesterol concentration (and/or serum cholesterol
      concentration) and LDL maximum diene formation was found using both methods and
      different sources of sera. With copper-induced oxidation, highly significant
      correlation coefficient r = 0.86, and with photo-sensitive oxidation r = 0.84
      were noted. The data standardized to protein unit showed a reduced but still
      significant correlation. The extent of LDL oxidation was also closely related to
      preformed dienes, i.e., to the data obtained before the start of oxidation (r =
      0.91). The rate of LDL oxidation was positively linked to LDL cholesterol using
      both oxidation methods but with photo-sensitive oxidation the rate was much
      higher. The lag time was inversely related to LDL cholesterol (standardized data)
      with Cu2+ induced oxidation but it was absent in the photosensitive oxidation. In
      animals known to be resistant to spontaneous atherosclerosis (rats, guinea pigs)
      a prolonged lag time, markedly reduced diene formation and lower LDL cholesterol
      in LDL in parallel was demonstrated. The fact that, using various methods
      (epidemiology, arteriography, autopsy), the cholesterol level in men was found
      positively linked to atherosclerosis development on the one hand, and positively
      associated to oxidation of human LDL on the other, strongly supports the concept
      on the important role of LDL oxidative modification in this pathological process.

PMID- 7827140
TI  - Characterization of amyloid A protein in human secondary amyloidosis: the
      predominant deposition of serum amyloid A1.
AB  - Serum amyloid A protein (SAA) is the plasma precursor for amyloid A protein (AA),
      the subunit protein in amyloid deposits of secondary or reactive amyloidosis.
      Several forms of acute phase SAA have been identified in human plasma. To
      elucidate whether one of these forms of SAA predominates in the formation of AA
      amyloid deposits, the amino acid sequence of the subunit protein in six cases of
      reactive amyloidosis was investigated. Minimal heterogeneity was present at the N
      terminus as all samples started with residue 1, 2, or 3 of SAA. The C-terminus,
      however, was more heterogeneous with the AA protein in each case terminating at
      multiple sites from residue 58 to 84 of SAA. Since less than 20% of the AA
      protein in each case contained sequence past residue 67 of SAA, the sequence and
      recovery of tryptic peptides containing residues 52, 57, and 60 where human SAA1
      and 2 differ was used to determine the relative amounts of SAA1 and 2 present.
      One sample contained only SAA1 sequence, four contained approx. 11% or less of
      SAA2 sequence, and the sixth contained 24-33% of SAA2 sequence. Thus, while five
      of the six AA samples contained both SAA1 and 2, the predominant form in all
      cases was SAA1. In three of the six cases, the protein defensin was isolated
      along with the AA protein from the fibrils. This may suggest neutrophil
      involvement in SAA processing to AA fibrils.

PMID- 7827141
TI  - Importance of ornithine transcarbamylase (OTC) deficiency in small intestine for
      urinary orotic acid excretion: analysis of OTC-deficient spf-ash mice with OTC
      transgene.
AB  - We report the effect of the ornithine transcarbamylase (OTC) transgene composed
      of 1.3 kb of the 5' flanking region of the rat OTC gene fused to rat OTC cDNA on
      urinary orotic acid excretion in OTC-deficient spf-ash (sparse-fur with abnormal
      skin and hair) mice during overnight-starvation and nitrogen loading. During
      starvation, spf-ash mice with about 6% and 2% of control levels of OTC activity
      in the liver and small intestine excreted a large amount of orotic acid in the
      urine. Transgenic spf-ash mice with about 10% and 30% of the control OTC
      activities in the liver and small intestine did not excrete more than the normal
      level of orotic acid. Accidental parasitization of transgenic spf-ash mice with
      ticks (Myocoptes musculinus) resulted in decrease of the OTC activities in the
      liver and small intestine to the levels in spf-ash mice, and increased excretion
      of orotic acid. During extermination of the ticks, the mice showed varied levels
      of OTC activity and orotic acid excretion. On nitrogen loading, transgenic spf
      ash mice as well as spf-ash mice excreted larger amounts of orotic acid, while
      control mice showed no increase in its excretion. The levels of urinary orotic
      acid were inversely correlated to the logarithms of the OTC activities in the
      liver and small intestine, the correlation being significantly higher with
      intestinal OTC than with hepatic OTC activity. These results suggest that the
      level of OTC activity in the small intestine is important for production of
      orotic acid.

PMID- 7827142
TI  - Normal sensitivity of Na+/K(+)-ATPase isolated from brain and kidney of
      spontaneously hypertensive rats to sodium, ouabain or mercury.
AB  - Genetically hypertensive rats are excellent animal models for investigating
      putative Na+/K(+)-ATPase alterations associated with the disease. Highly purified
      Na+/K(+)-ATPase preparations from these animals have not yet been examined.
      Na+/K(+)-ATPases of two strains of spontaneously hypertensive rats, the Milan
      hypertensive strain (MHS) and the spontaneously hypertensive rat (SHR) were
      characterized in comparison with enzymes isolated from their matched normotensive
      controls; the sensitivity to Na ions as well as the shape and span of the
      inhibition curves for ouabain and mercury of the isolated Na+/K(+)-ATPases were
      compared. No functional changes between the purified 'normotensive' and
      'hypertensive' Na+/K(+)-ATPases from brain and kidney were detected ruling out
      drastic structural alterations of the transport system in these two organs of
      diseased animals.

PMID- 7827143
TI  - Lymphoma.

PMID- 7827144
TI  - Cancer in AIDS.

PMID- 7827145
TI  - Gynecologic cancer.

PMID- 7827146
TI  - Will new treatment strategies improve the control of non-Hodgkin's lymphomas?

PMID- 7827147
TI  - Pathology of Hodgkin's disease.
AB  - This review addresses several current questions about Hodgkin's disease (HD): 1)
      Does HD represent a single disease or multiple diseases? 2) What is the role of
      cytokines in HD? 3) What is the nature of the Reed-Sternberg cell? 4) How are
      Epstein-Barr virus (EBV) and oncogenes (bcl-2, c-myc, and p53) involved in the
      pathogenesis of HD? Nodular lymphocyte predominance HD appears to be a distinct
      clinicopathologic entity. Cytokines attract inflammatory cells, induce fibrosis,
      upregulate oncogenes and adhesion molecules, cause systemic symptoms, and mediate
      immune suppression. Reed-Sternberg cells are derived from B and T lymphocytes in
      most instances, although an alternative origin from a follicular dendritic
      reticulum cell has been proposed. EBV is an etiologic agent in some but not all
      HD cases. EBV gene products confer a growth advantage on Reed-Sternberg cells.
      The bcl-2 and p53 oncogenes protect Reed-Sternberg cells from apoptosis and are
      not directly upregulated by EBV.

PMID- 7827148
TI  - New imaging techniques in staging lymphomas.
AB  - A variety of imaging modalities are used to evaluate patients with lymphoma,
      mainly Hodgkin's disease. During the past few years, the improvement of
      diagnostic techniques has had a great impact on both staging and patient
      treatment. This review of the current status of imaging presents the
      possibilities of available diagnostic tools in the assessment of lymphomatous
      involvement of different organs and apparatus, emphasizing those aspects that
      might influence patient management and treatment. For central nervous system
      lymphomas, pre- and postcontrast computed tomography and magnetic resonance have
      completely replaced other radiologic methods. Similarly, because it seems clear
      that computed tomography will replace lymphography by the end of this decade,
      just as computed tomography and magnetic resonance imaging are expected to
      entirely replace staging laparotomy, the possibilities of these diagnostic tools
      and their impact on diagnosis and follow-up are also discussed.

PMID- 7827149
TI  - Modern combined modality management of Hodgkin's disease.
AB  - The combination of chemotherapy and irradiation in the management of patients
      with Hodgkin's disease is being reported with increased frequency. In some
      situations, higher cure rates have been achieved with combined modality. In other
      situations, a reduction or modification of one or both modalities has reduced the
      acute toxicity (and later morbidity) of successful therapy.

PMID- 7827150
TI  - New active drugs in the treatment of lymphomas.
AB  - Lymphomas include a vast number of pathologic conditions in which the search for
      new active drugs follows different routes. Hodgkin's disease and high-grade non
      Hodgkin's lymphoma are very sensitive to chemotherapy, responding well to
      existing regimens; the inability to cure seems to be caused by acquired drug
      resistance. Newer strategies using classic chemotherapeutic agents and the use of
      modulators of resistance are the main focus of research in these malignancies.
      For indolent lymphomas, the inability to cure may be caused by the difficulty in
      eradicating completely an apparently sensitive disease. The search for new drugs
      in this field has focused on chemotherapeutic agents with new mechanisms of
      action, among which the purine analogues are the most important novelty, and on
      biologic therapy. There is evidence of activity of drug targeting, using
      monoclonal antibodies, immunotoxins, and radioimmunotherapy. Their role in the
      treatment of these malignancies will probably be different from that of
      traditional drugs, perhaps in the context of eradication of minimal residual
      disease after effective conventional therapy.

PMID- 7827151
TI  - AIDS-related malignancies.

PMID- 7827152
TI  - Epidemiology of AIDS-related malignancies.
AB  - HIV infection is known to increase the incidence of Kaposi's sarcoma and non
      Hodgkin's lymphoma. Kaposi's sarcoma preferentially affects homosexual men and
      risk varies by geographic area, suggesting there is an environmental cofactor for
      Kaposi's sarcoma in addition to HIV. Despite intensive investigation, the
      responsible cofactor has not been conclusively identified. HIV-associated non
      Hodgkin's lymphoma affects all HIV transmission groups, and non-Hodgkin's
      lymphoma risk increases with duration of HIV infection and age. Epstein-Barr
      virus has been implicated in the pathogenesis of this tumor, but the precise
      mechanisms have not been worked out. Cervical cancer and anal cancer have a less
      certain association with HIV infection and immunodeficiency, although epithelial
      dysplasia at these sites does seem to be HIV-related. Children with HIV infection
      are additionally affected by increased incidence of leiomyosarcoma and benign
      leiomyoma, whereas adults with HIV infection do not seem particularly susceptible
      to this tumor, perhaps because of hormonal or growth-promoting factors. Apart
      from these specific disease associations, HIV infection and related
      immunodeficiency do not result in a generalized tumor diathesis. Prevention and
      management of HIV-associated cancers are becoming increasingly important as the
      HIV epidemic continues to grow.

PMID- 7827153
TI  - Pathogenesis of HIV-related Kaposi's sarcoma.
AB  - Infection with HIV-1 is associated with a 7000-fold increase in the incidence of
      Kaposi's sarcoma (KS). Some studies suggest that the risk of KS in HIV infection
      is increased with certain sexual practices and that a sexually transmitted agent
      could be involved. Exposure to this agent apparently alters both the morphology
      and growth regulation of the KS progenitor cells. These changes include the
      expression of the different cytokine receptors and the acquisition of autocrine
      growth loops. Perturbations of multiple cytokines during HIV infection, including
      oncostatin-M, interleukin-1 beta, and tumor necrosis factor-alpha, alter the
      subsequent growth of KS. These studies suggest that control of cytokine
      perturbations or the underlying HIV-1 infection could result in a significant
      reduction in the growth rate of AIDS-related KS.

PMID- 7827154
TI  - Biologic aspects of AIDS-related lymphoma.
AB  - Lymphoma is one of the defining manifestations of AIDS. Most of these
      lymphoproliferations are high-grade B-cell non-Hodgkin's lymphoma. Unlike
      lymphoproliferations that arise in other settings of immunodeficiency, HIV
      related lymphomas have a variable association with Epstein-Barr virus (EBV) and
      also contain alterations in c-myc and p53. EBV infection appears to precede
      clonal expansion, and its latent expression pattern (Epstein-Barr nuclear
      antigen1+/Epstein Barr nuclear antigen 2-/latent membrane protein+) is unique
      among non-Hodgkin's lymphomas. Both EBV types A and B are present in HIV-related
      lymphomas. Mutations in c-myc include translocations and point mutations. Other
      altered loci include ras and bcl-6. Although all of these somatic alterations can
      be detected in lymphomas arising in the general population, their accumulation in
      a relatively short period (6 to 8 years) after HIV infection suggests an
      acceleration of underlying mechanisms.

PMID- 7827155
TI  - Other cancers in HIV-infected patients.
AB  - There is evidence that, in addition to Kaposi's sarcoma, high-grade non-Hodgkin's
      lymphoma, and invasive cervical carcinoma (the only malignancies diagnostic per
      se of AIDS), other tumors have been occurring in the HIV setting, often with
      peculiar clinicopathologic characteristics. Because the survival of patients with
      HIV infection has improved owing to the better prevention and management of
      opportunistic infections, it is highly likely that these malignancies will
      increase in the next few years. The study of these tumors will help us better
      understand the relationship between the prolonged immunosuppression and the
      development of tumors.

PMID- 7827156
TI  - Advances in the biology of gynecologic cancer.
AB  - This review discusses recent insights into the roles of the p53 tumor-suppressor
      gene and growth factors in the development of ovarian cancer and describes the
      genes implicated in familial ovarian cancer syndromes related to the MSH2 (Lynch
      II) and BRCA1 (breast and ovarian cancer) genes. Evidence of the monoclonality of
      ovarian cancer, which contrasts with data supporting the polyclonal origin of
      primary peritoneal carcinoma, is presented. Finally, the roles of the human
      papillomavirus and the HIV virus in the etiology of cervical cancer are analyzed
      in view of the growing importance of this HIV-associated cancer and the poor
      outcome in these patients.

PMID- 7827157
TI  - Surgery for gynecologic cancer.
AB  - Surgery is an integral part of staging procedures for ovarian, endometrial, and
      vulvar cancers, with a move toward surgicopathologic rather than clinical staging
      in cervical cancer. Morbidity can be reduced without compromising patient cure by
      individualizing surgery for patients with early vulvar cancer, and reproductive
      potential can be maintained in some women with early ovarian cancer. The place of
      prophylactic oophorectomy and primary and secondary surgery in ovarian cancer
      remain controversial and await prospective study. Recent developments in
      laparoscopic techniques have been applied to a number of problems in gynecologic
      cancer surgery, and the feasibility of laparoscopic lymphadenectomy and radical
      pelvic surgery has been demonstrated. Care must be taken, however, to ensure that
      the tenets of surgical oncology are not sacrificed in order to offer minimal
      access surgery to women with gynecologic cancer.

PMID- 7827158
TI  - Combined modality treatment for carcinomas of the uterine cervix and vulva.
AB  - Several attempts have been made during the preceding year to apply multimodality
      approaches to the treatment of carcinomas of the uterine cervix and the vulva.
      Neoadjuvant chemotherapy may render more cervical tumors resectable, but it does
      not necessarily improve curability when compared with similarly staged patients
      treated with definitive pelvic irradiation alone. Neither concurrent
      chemoradiotherapy nor adjuvant chemotherapy following hysterectomy have been
      shown to be superior to definitive radiotherapy in prospective randomized trials
      of cervical cancer patients. Exciting data continue to be reported for the
      integration of chemotherapy, radiotherapy, and conservative surgery in the
      management of vulvar cancer. Such initiatives are contingent on the close
      cooperation of oncologists during the design and implementation of prospective
      trials.

PMID- 7827159
TI  - Advances in the chemotherapy of gynecologic cancer.
AB  - By combining paclitaxel and cisplatin in treatment schedules for the initial
      treatment of advanced ovarian cancer, new hope has been engendered that we can
      further improve survival. With premedication, paclitaxel can be administered
      safely as a short infusion. The combination of paclitaxel and carboplatin is
      recognized as an alternative to the combination of cisplatin and paclitaxel, and
      is now under study to define its role in future treatment programs. Other new
      drugs have been recognized as active in platinum-resistant disease, including
      docetaxel and gemcitabine. Renewed interest arose for a chronic low dose of oral
      etoposide in platinum-refractory ovarian cancer. The results obtained with
      chemotherapy in cervical cancer have always been modest, and no combinations have
      been shown to result in improved survival rates as compared with single drugs.
      The novel biologic regimen, using retinoids and interferon, was confirmed to be
      active in locally advanced cervical cancer. In trophoblastic disease, the Charing
      Cross scoring system is a relevant pretreatment scoring system compared with the
      International Federation of Gynecology of Obstetrics staging. Careful recognition
      of prognostic subgroups can prevent under- or overtreatment.

PMID- 7827160
TI  - Breast.

PMID- 7827161
TI  - Therapeutic modalities.

PMID- 7827162
TI  - Epidemiology, prevention, and early detection of breast cancer.
AB  - Advances in the past year in understanding the etiology, early detection, and
      prevention of breast cancer are reviewed. Reports suggest that exogenous hormone
      therapy is associated with only moderate or no excess risk of breast cancer.
      Studies examining the association between exposure to organochlorine compounds
      and the risk of breast cancer are inconsistent and further investigations are
      required. The report by the International Workshop of Screening for Breast Cancer
      emphasizes the benefit in reducing breast cancer mortality to be gained by
      regular screening among women aged 50 years and older. Age is the strongest
      predictor of breast cancer risk, yet screening rates tend to diminish with age.
      Chemoprevention trials for the primary prevention of breast cancer are underway
      in North America and Europe. Agents under investigation include tamoxifen and
      fenretinide. The risks and benefits of tamoxifen therapy continue to be clarified
      with reports from a pilot prevention trial and follow-up of participants of prior
      adjuvant treatment trials. A beneficial effect in reducing cardiac morbidity has
      been observed among women taking 40 mg/d of tamoxifen for at least 2 years.
      Several studies demonstrated the increased risk of endometrial pathologic
      changes, including endometrial cancer associated with tamoxifen therapy. Because
      of the uncertainty of net risks and benefits, close monitoring for adverse side
      effects should be incorporated into ongoing prevention trials.

PMID- 7827163
TI  - Pathology of preinvasive and excellent-prognosis breast cancer.
AB  - Concern about the recognition of especially good prognoses continues to be
      resolute among those who decide, with patients, the course of treatment.
      Prognostic considerations are paramount in this planning process, and should
      emphasize precision in case definition and repeated verification in comparable
      studies. Excellent-prognosis invasive lesions, subtyping of ductal carcinomas in
      situ, and premalignant indications within otherwise benign breast biopsy
      specimens are highlighted in this review.

PMID- 7827164
TI  - The biology of breast cancer.
AB  - The progression from normal breast epithelium to metastatic breast cancer is a
      complex, multistep process. Initially, genetic alterations are thought to confer
      a growth advantage to individual cells by decreasing tumor-suppressor gene
      activity or increasing oncogene activity, or both. Further alterations result in
      the development of cell clones that have the ability to invade adjacent tissue,
      establish metastatic deposits, and evade immune surveillance. At some point in
      this process, these malignant cell clones also lose the normal ability to respond
      to hormonal growth regulatory signals. Recent advances in understanding the
      genetic alterations, the loss of normal growth regulation, and the development of
      metastatic potential in breast cancer are reviewed. Factors related to the
      immunobiology of breast cancer are also discussed.

PMID- 7827165
TI  - Surgery of early breast cancer.
AB  - Randomized clinical trials evaluating local treatments for early breast cancer
      have provided new data on the long-term morbidity and cause-specific mortality
      associated with radiotherapy combined with different types of mastectomy. The
      difficulty surgeons have in determining optimal integration of surgery and
      radiotherapy for breast preservation is demonstrated by the wide variation of
      radiotherapy schedules, lack of interpretable data to justify a radiotherapy
      "boost," and data from a randomized trial suggesting that radiotherapy applied
      only to the excision site might be sufficient. The use of cytology aspirates for
      tumor grading, the prognostic importance of vascular invasion, and new tumor
      markers and cancer cells in bone marrow at diagnosis are all reported. New data
      came from attempts to identify an axillary sentinel node at surgery for breast
      cancer. Studies of connective tissue disorders in women with silicone implants
      failed to find evidence of increased risk, but 3-year follow-ups confirmed that
      surgeons who preferred mastectomy are more likely to have anxious, depressed
      patients.

PMID- 7827166
TI  - Radiation therapy for breast cancer.
AB  - Prospective randomized studies continue to dominate issues of local regional
      radiation therapy for breast cancer. The National Surgical Adjuvant Breast and
      Bowel Project, designed to assess the role of radiation therapy in the management
      of breast-conserving surgery for duct carcinoma in situ, has published
      preliminary results. These results indicate that the use of radiation therapy
      decreases the local recurrence rate in women with this disease, with a short
      median follow-up for the entire group so far. The Milan Cancer Institute likewise
      first reported on their trial assessing the role of radiation therapy in early
      invasive breast cancer, following a quadrantectomy procedure in the breast as
      well as an axillary node dissection. Again, radiation therapy significantly
      decreased the local recurrence rate in the treated breast compared with
      observation alone. Several important retrospective analyses continue to search
      for prognostic indicators that might effect the outcome of patients treated with
      breast-conserving surgery and irradiation. The issue of early age, as well as the
      issue of sequencing needed adjuvant chemotherapy with whole-breast irradiation
      was the subject of several articles. Other researchers focused on methods of
      detection of failure in the irradiated breast, including several innovative
      studies using magnetic resonance imaging. Documentation of radiation-related
      treatment sequelae is also reviewed, along with a retrospective study assessing
      the palliative role of strontium-89 isotope treatment of women with widespread
      metastatic bone lesions.

PMID- 7827167
TI  - Systemic adjuvant therapy for breast cancer.
AB  - Systemic adjuvant therapy reduces the mortality due to breast cancer to a modest
      extent. Current research directions focus on both increasing the efficacy of
      therapy, predominantly by increasing the intensity of treatment, and attempting
      to reduce toxicity by treating only those patients at significant risk of
      relapse. Improved understanding of both the metastatic process and the mechanisms
      by which cytotoxic treatments exert their effects hold the promise for more
      effective treatments in the future. Cost-benefit analyses demonstrate the
      relative cost-effectiveness of adjuvant systemic therapies for patients at
      significant risk of recurrence, for whom the effectiveness of treatment is
      substantial.

PMID- 7827168
TI  - Therapy for metastatic breast cancer.
AB  - Our understanding of mechanisms of resistance to endocrine treatment has
      increased; they include mutations in steroid receptors and altered metabolism of
      tamoxifen. Tamoxifen and progestogens appear to have similar efficacies for first
      line endocrine treatment, but high doses of progestogens have been shown to give
      less cost-effective results compared with conventional doses. Numerous new
      endocrine and cytotoxic agents have been reported, but no major new treatments
      have been identified. High-dose chemotherapy for metastatic disease remains
      experimental. The concept of estrogen recruitment to enhance chemosensitivity has
      not been corroborated. Prior adjuvant systemic treatment renders treatment of
      relapsed breast cancer less effective.

PMID- 7827169
TI  - Quality of life and other psychosocial issues in breast cancer.
AB  - Over the past year, quality of life among patients with breast cancer has
      continued to be a noteworthy area of research. Several articles related to
      provider-patient communication are also included in this review. Reports on the
      psychologic distress and cancer screening practices of spouses and other
      relatives of patients with breast cancer are noted. This review summarizes and
      critiques publications in these three areas.

PMID- 7827170
TI  - Antisense oligodeoxynucleotides.
AB  - Oligodeoxynucleotides have been proposed as both in vitro and in vivo inhibitors
      of gene expression because of the specificity of Watson-Crick base pair
      hybridization. Phosphodiester oligodeoxynucleotides (normal DNA) cannot be used
      as drugs because they are nuclease sensitive. Significant efforts have been made
      to study phosphorothioate oligodeoxynucleotides, which have a sulfur atom
      substituted for one of the phosphate oxygen atoms at a nonbridging position.
      These oligodeoxynucleotides are nuclease resistant, and over the past year they
      have entered clinical trials. They have also been extensively examined in vitro
      and have been targeted to the bcr-abl and bcl2 messenger RNAs among others.
      Methods to maximize the intracellular oligodeoxynucleotide concentration have
      also been devised. However, significant problems remain, including the
      significant nonsequence specificity of phosphodiester oligodeoxynucleotides as
      well as questions of oligodeoxynucleotide uptake into and compartmentalization
      within cells. An improvement of our understanding of these phenomena is critical
      to the elaboration of this technology into a clinical therapeutic modality.

PMID- 7827171
TI  - Is p-glycoprotein a potential target for reversing clinical drug resistance?
AB  - The overexpression of MDR1 p-glycoprotein has been associated with the emergence
      of clinical drug resistance for a number of malignancies, especially those of the
      hematopoietic variety. Given this observation, the question arises regarding the
      suitability of p-glycoprotein as a target for reversing multiple drug resistance
      (MDR) and improving therapeutic outcome. This review focuses on the role of p
      glycoprotein in hematopoietic malignancies and proposes that these malignancies
      serve as a prototype for further investigations. The status of clinical studies
      to reverse or circumvent clinical MDR is also discussed. Recommendations are made
      regarding the kinds of tumors to be studied, the type of chemosensitizer desired,
      and the design of clinical protocols required to answer the question of whether p
      glycoprotein is a suitable target to reverse or prevent clinical MDR.

PMID- 7827172
TI  - Antiviral and anticancer ribozymes.
AB  - Molecular biologists are beginning to apply the site-specific RNase properties of
      ribozymes to gene therapy for HIV infection and cancer. Requirements for
      substrate recognition and cleavage are being finely mapped. Methods of augmenting
      intracellular cleavage and of dissecting observed discrepancies between in vitro
      and cellular activity are being explored. Antiviral efficacy against HIV type 1
      has been seen in tissue culture for both hammerhead and hairpin ribozymes, and a
      phase I clinical trial for ex vivo T-cell gene therapy is planned. Oncogene
      transcripts, such as the bcr/abl fusion messenger RNA and ras, have also been
      targeted with ribozymes.

PMID- 7827173
TI  - Systemic administration of new therapeutic radioisotopes, including phosphorus,
      strontium, samarium, and rhenium.
AB  - New advances in systemic radionuclide therapy have increased the number of
      treatment options available for patients with painful osseous metastases. This
      form of therapy has three major appeals: 1) it addresses all sites of
      involvement; 2) selective absorption into bone limits irradiation of normal
      tissues; and 3) as a result, toxicity may be reduced and the therapeutic ratio
      improved. The clinical experience with radioactive phosphorus, strontium,
      samarium, and rhenium are reviewed. To date, the best studied and the only Food
      and Drug Administration approved agent is strontium-89. About 60% to 90% of
      patients treated with strontium-89 respond with complete or partial relief of
      pain for a median duration of 6 months. Large, prospectively randomized clinical
      trials have established the efficacy of strontium-89 as a first-line therapy and
      as an adjuvant to external-beam radiotherapy. Particularly advantageous is its
      usefulness in situations in which external-beam radiotherapy options have been
      exhausted and normal tissue tolerance has been reached. Newer
      radiopharmaceuticals are still under investigation.

PMID- 7827174
TI  - Human tumor vaccines and genetic engineering of tumors with cytokine and
      histocompatibility genes to enhance immunogenicity.
AB  - Genetically engineered tumor cells can be used as vaccines in order to stimulate
      an immune response. To date, tumor cells have been modified in vitro so that they
      secrete cytokines or express histocompatibility molecules that they naturally
      fail to express. These tumor cells differ in the types of immune responses they
      induce and in whether the responses have local or systemic efficacy. Many
      questions have been raised during the past year, including whether allogeneic or
      autologous tumor cells should be employed and whether there may be a risk of
      inducing autoimmune disease along with the antitumor response. Nevertheless,
      because of the paucity of available therapies for patients with advanced cancer,
      investigators must attempt to refine the approaches used in order to minimize
      patient risk while maximizing tumor cell destruction.

PMID- 7827175
TI  - Apoptosis as a goal of cancer therapy.
AB  - The elimination of a tumor cell population by exposure of the tumor to lethal
      doses of drugs or radiation is a well-established strategy in cancer therapy.
      Although better cytotoxic chemo- and radiotherapy regimens, coupled with the
      discovery of new chemotherapeutics, will continue to improve the effectiveness of
      such treatments, recent discoveries in the field of cell death promise to have a
      major impact in this area. Because apoptosis is an active process under molecular
      control, information concerning the regulation and execution of this type of cell
      death should lead to the development of more effective means of eliminating
      malignant cell populations. In addition, discovering how normal controls on
      apoptosis can fail should also improve our understanding of how tumors develop.

PMID- 7827176
TI  - Antibodies in the treatment of human cancer.
AB  - Monoclonal antibody-based therapy has the theoretic appeal of selective targeting
      of tumor cells. Most promising is the use of toxins and radioisotope
      immunoconjugates in the treatment of hematologic malignancies. Obstacles to
      effective treatment have been defined and solutions are being pursued. The future
      use of this therapeutic strategy will be determined by creative approaches to
      enhance delivery, decrease immunogenicity, and maximize potency of antibody
      reagents.

PMID- 7827177
TI  - The role of positron emission tomography imaging in early assessment of the
      antitumor impact of biologics and cytotoxics.
AB  - In the evaluation of protocols for patients with cancer, clinicians are
      increasingly searching for diagnostic tests that will give an accurate indication
      of response to therapy and predict outcome. Although standard radiologic
      modalities such as computed tomography and magnetic resonance imaging can
      localize sites of disease and monitor changes in size of lesions, they cannot
      reliably determine tumor viability. Positron emission tomography provides the
      opportunity to quantitate parameters of tumor metabolism. There are numerous
      studies in the literature reviewing a wide variety of malignancies, and this is
      an exciting area of ongoing research.

PMID- 7827178
TI  - Physician/nurse relationship revisited.

PMID- 7827179
TI  - Technique survival in continuous ambulatory peritoneal dialysis.

PMID- 7827180
TI  - Excellent technique survival on home peritoneal dialysis: results of a regional
      program.
AB  - OBJECTIVE: To examine peritoneal dialysis technique survival in our regional,
      continuous ambulatory peritoneal dialysis (CAPD) program. DESIGN: Retrospective
      analysis. SETTING: Tertiary care dialysis program at an academic medical center.
      PATIENTS: 155 patients representing all those in the peritoneal dialysis program
      between October 1, 1987 and October 1, 1990. OUTCOME MEASURES: The study analyzed
      patient and technique survival as well as the reasons for discontinuation of
      dialysis. In addition, the incidence and type of peritonitis and exit-site
      infection were also analyzed. RESULTS: Three-year actuarial patient survival was
      66% and three-year technique survival was 86%, with data censored for death and
      transplant patients. Fifty-seven percent of transfers to hemodialysis were due to
      peritonitis, usually fungal or multiorganism bacterial. Only 1 patient failed due
      to exit-site and tunnel infection, and 1 due to inadequate dialysis. The catheter
      removal rate was 0.04 per patient-year. CONCLUSIONS: Excellent CAPD technique
      survival can be achieved if exit-site and tunnel infection rates are low.

PMID- 7827181
TI  - Bidirectional solute transport in peritoneal dialysis.
AB  - OBJECTIVE: Three transport components are involved in solute transport in
      peritoneal dialysis: diffusion, convective transport, and peritoneal reabsorption
      of dialysate (fluid and solutes). The relative impact of these components on
      measureable transport characteristics (dialysate-to-plasma concentration ratio,
      diffusive mass transport coefficient, unidirectional clearances) may depend on
      the direction of solute transport, that is, from blood to dialysate or vice
      versa. The application of the bidirectional characteristics for the assessment of
      fluid and solute transport in peritoneal dialysis is reviewed and evaluated. DATA
      SOURCES: Theoretical analysis as well as computer simulations were applied to
      discuss available data from our own studies on peritoneal transport as well as
      from published clinical, experimental, and theoretical studies in the same field.
      STUDY SELECTION: Thirty-three relevant clinical and experimental studies as well
      as theoretical analyses derived from the literature were reviewed. DATA
      EXTRACTION: Data were extracted to highlight current controversies in the
      literature concerning the assessment of peritoneal reabsorption rate based on
      transport of macromolecules, middle molecules, and small solutes. RESULTS:
      Peritoneal reabsorption is the main component of the transport of macromolecules
      infused into the peritoneal cavity, and these solutes are currently being used
      for the assessment of the rate of reabsorption. In contrast, diffusive transport
      and peritoneal reabsorption cannot be experimentally discriminated for small
      solutes which exhibit negligible sieving through the membrane in convective
      transport (i.e., solutes with sieving coefficient equal to 1). For middle
      molecules each transport component may be of importance and may have an
      independent impact on bidirectional transport characteristics. CONCLUSIONS:
      Middle molecules, with sieving coefficients substantially less than 1, may be
      applied for estimation of peritoneal reabsorption rate using bidirectional
      transport characteristics, as apparent diffusive mass transport coefficients or
      unidirectional clearances. However, an independent measurement of sieving
      coefficient is necessary for this method.

PMID- 7827182
TI  - Prosthetic mesh repair of multiple recurrent and large abdominal hernias in
      continuous ambulatory peritoneal dialysis patients.
AB  - OBJECTIVE: The aim of this study was to find out whether prosthetic mesh repair
      of recurrent and large abdominal hernias in continuous ambulatory peritoneal
      dialysis (CAPD) patients is effective in maintaining them on CAPD. DESIGN:
      Retrospective analysis of case notes over a period of 5 years. SETTING: Single
      renal unit of a university hospital. PATIENTS: Forty-six of 217 CAPD patients
      (16%) had their hernias repaired. Among them, 5 women in whom hemodialysis was
      not possible had multiple or large hernias repaired with polypropylene (PP) mesh.
      RESULTS: Radical repair was achieved by a modified operation consisting of a
      conventional hernioplasty complemented by a supporting prostetic overlay mesh,
      without discontinuation of CAPD. The patients continued CAPD for a mean period of
      17.6 months without hernia recurrence. Two patients died in the twelfth and
      fifteenth post-operative month due to cardiac arrest and hepatic failure,
      respectively, and the remaining 3 are alive and have been doing well on CAPD for
      13, 14, and 21 months. CONCLUSIONS: Prosthetic mesh repair of large recurrent
      hernias in CAPD patients with vascular access problems seems to be a valuable
      method to maintain them on this renal replacement therapy.

PMID- 7827183
TI  - Anabolic steroids in the treatment of malnourished CAPD patients: a retrospective
      study.
AB  - OBJECTIVE: To assess the effect of anabolic steroids on malnutrition of
      continuous ambulatory peritoneal dialysis (CAPD) patients. DESIGN: Retrospective
      analysis of medical records, charts, and computer-generated laboratory and
      medication data. SETTING: Peritoneal Dialysis Unit of The Toronto Hospital.
      PATIENTS: Thirteen patients with moderate to severe malnutrition who had received
      nandrolone decanoate (ND) intramuscularly (IM) for at least three months. Nine of
      these patients (group A), with a mean age of 59.4 years, received only ND (100
      200 mg IM monthly). Group B consisted of 4 patients (mean age 74.0 years) who, in
      addition to ND, received intraperitoneal (IP) amino acids. RESULTS: In group A,
      serum albumin, while declining before ND treatment (34.4 +/- 3.2 to 31.5 +/-
      3.35, x +/- SEM, g/L at -2 and 0 months), showed a progressive and significant (p
      < 0.001) increase during treatment, sustained up to the third month (36.57 +/-
      1.51). In group B, serum albumin did not increase significantly (30.25 +/- 2.62,
      30.75 +/- 1.9, and 31.5 +/- 4.8, mean +/- SEM, g/L at -2, 0, and +3 months,
      respectively. In group A, serum creatinine was increased significantly (p < 0.01)
      from 0 to +3 months (731 +/- 185 to 938 +/- 92.5 mmol/L). Blood urea,
      bicarbonate, and total protein levels did not change significantly. In group B,
      serum creatinine fluctuated considerably with an insignificant trend to rise.
      Blood urea showed a steady trend to increase without reaching statistical
      significance. In relation to time 0, bicarbonate levels (28.7 +/- 3.3) were
      decreased significantly (p < 0.05) (27 +/- 0.8, 24.6 +/- 1.5, and 25 +/- 1 mEq/L,
      at +1, +2, and +3 months, respectively). CONCLUSIONS: Nandrolone decanoate alone,
      in relatively low doses, exerted a definite anabolic effect in 9 malnourished
      CAPD patients. The lack of a similar effect in 4 patients, who in addition to ND
      received amino acids IP, could be explained by the low dose of ND, the concurrent
      acidosis, the severity of malnutrition, and the older age of this group.

PMID- 7827185
TI  - Volume of distribution and fractional clearance of urea in amputees on continuous
      ambulatory peritoneal dialysis.
AB  - OBJECTIVES: To demonstrate the effects of amputation on the estimates of urea
      volume of distribution (V) and KT/V urea in continuous ambulatory peritoneal
      dialysis (CAPD) patients and to present a method for correcting the errors
      created by the uncorrected anthropometric formulas estimating V. DESIGN: (1) A
      mathematical analysis of the error and the correction proposed was performed. (2)
      Urea kinetic modeling with uncorrected and corrected estimates utilizing both the
      Watson and the Hume anthropometric formulas was performed in amputees on CAPD.
      SETTING: Subjects were recruited from four dialysis units in one city: one
      Veterans Affairs unit, one university-affiliated unit, and two community units.
      PATIENTS: Fourteen amputees on CAPD:12 with unilateral leg amputation and 2 with
      bilateral leg amputation, at the same length of the leg, were studied.
      INTERVENTIONS: Urea kinetic studies were performed in 24-hour drained dialysate
      and urine specimens. MAIN OUTCOME MEASURES: Uncorrected and corrected estimates
      of V and KT/V urea were compared to each other and to the predictions of the
      mathematical model. Body weights corresponding to uncorrected and corrected V
      estimates were compared to the actual body weights. RESULTS: (1) The mathematical
      model predicts that uncorrected estimates by the anthropometric formulas will
      falsely characterize unilateral amputees as leaner than they are and bilateral
      amputees as more obese than they are. (2) In unilateral amputees studied with the
      Watson formulas, uncorrected V was 0.546 +/- 0.023 L/kg and corrected V was 0.520
      +/- 0.023 L/kg (p < 0.001). Corresponding weekly KT/V urea values were 1.97 +/-
      0.14 and 2.07 +/- 0.14, respectively (p < 0.001). Similar results were obtained
      with the Hume formulas. In bilateral leg amputees studied with the Watson
      formulas, uncorrected V was 0.479 +/- 0.022 L/kg and corrected V was 0.514 +/-
      0.023 L/kg. Corresponding KT/V estimates were 2.11 +/- 0.45 and 1.96 +/- 0.14,
      respectively. The differences were even greater with the Hume formulas. Estimates
      of body weight calculated from corrected V values were equal to actual weight
      measurements, whereas those calculated from uncorrected V values were lower than
      actual body weight measurements in unilateral amputees, and much higher than
      actual body weight measurements in bilateral amputees. CONCLUSION: Uncorrected
      anthropometric estimates falsely characterize unilateral amputees as leaner than
      they actually are and bilateral amputees, amputated at the same leg length, as
      more obese than they actually are. Uncorrected KT/V estimates are, therefore,
      falsely low in unilateral amputees, and falsely high in bilateral amputees. The
      proposed correction of the anthropometric formulas provides estimates agreeing
      closely with dietary estimates of body composition. Further studies are needed to
      define the accuracy of the corrected formulas.

PMID- 7827184
TI  - Synthesis of phospholipids by human peritoneal mesothelial cells.
AB  - OBJECTIVE: To assess the capacity of cultured human peritoneal mesothelial cells
      to synthesize choline-containing phospholipids. The study compares the
      phospholipids secreted from cultured cells with those which we, and others, have
      identified in the dialysate of patients treated by continuous ambulatory
      peritoneal dialysis (CAPD). PATIENTS: CAPD effluent was collected from 8 patients
      who had been receiving CAPD treatment for at least 11 months and who had normal
      ultrafiltration. CELL CULTURES: Using human omental tissue, homogeneous cultures
      of mesothelial cells were established. METHODS: Synthesis of phospholipids by
      mesothelial cells was assessed following incubation with [methyl-14C] choline
      chloride--a precursor capable of being incorporated into phosphatidylcholine
      (PtdCho) and sphingomyelin. Lipids from CAPD effluent, cultured cells, and cell
      medium were extracted in chloroform/methanol. Phospholipids were separated and
      identified by thin layer chromatography. Synthesis and secretion of PtdCho and
      other choline-containing lipids by the mesothelial cells were determined by beta
      scintillation counting of the appropriate bands, while the fatty acid composition
      of the phospholipids was ascertained by gas liquid chromatography. RESULTS:
      Synthesis and secretion of PtdCho by mesothelial cells were observed during a 96
      hour period. When maintained in medium replete with essential fatty acids, the
      fatty acid composition of the PtdCho synthesized by cultured mesothelial cells
      closely resembled that isolated from the peritoneal cavity. CONCLUSION: The
      demonstration of phospholipid secretion from mesothelial cells, with a fatty acid
      composition similar to the phospholipids isolated from peritoneal dialysate,
      lends added support to the hypothesis that the mesothelial cells are the source
      of the peritoneal phospholipids. As such they offer a useful experimental system
      in which to study peritoneal phospholipid synthesis.

PMID- 7827186
TI  - Anabolic steroids and malnutrition in chronic renal failure.
AB  - OBJECTIVE: To determine whether anabolic steroids are useful in the management of
      the malnutrition of chronic renal failure. DATA SOURCE: Original research studies
      and book chapters about anabolic steroids and their use in uremia and various
      illnesses associated with malnutrition. We included studies that describe the
      benefits of anabolic steroids in the treatment of anemia and sexual dysfunction
      of chronic renal failure. Forty-two such studies were published between 1942 and
      1992. RESULTS: Anabolic steroids improve the nutritional status and sexual
      dysfunction of uremic men. In addition, anabolic steroids have a recognized place
      in the treatment of the anemia of chronic renal failure. CONCLUSIONS: Based on
      the findings of noncontrolled studies, one may conclude that anabolic steroids
      exert a beneficial effect in the malnutrition of renal failure. We believe that
      their efficacy should be established by controlled studies.

PMID- 7827187
TI  - Bicarbonate-based dialysis solution preserves granulocyte functions.
AB  - OBJECTIVE: Intraperitoneal phagocytes play an important role in local defense in
      preventing continuous ambulatory peritoneal dialysis (CAPD) peritonitis. This
      study therefore investigates the effect of the conventional lactate-based
      dialysis solution-pH 5.2 (LBDS-pH 5.2) and a bicarbonate-based dialysis solution
      (BBDS) on various cell functions. DESIGN: We studied C5a-induced actin
      polymerization (AP) as a measure of the cytoskeletal alteration, phagocytosis of
      zymosan particles, and chemotaxis in neutrophils incubated in either LBDS-pH 5.2,
      LBDS-pH 7.4, or BBDS-pH 7.4, comparing the data with cells treated with phosphate
      buffered saline-pH 7.4 (PBS-pH 7.4) as a control. SUBJECTS: Polymorphonuclear
      neutrophils (PMNs) were isolated from the blood of healthy donors and incubated
      with dialysis solution prior to the experiment. RESULTS: C5a-induced AP was
      dramatically inhibited in PMNs incubated in LBDS-pH 5.2, paralleled by a complete
      inhibition of phagocytosis and C5a-induced chemotaxis. In comparison, BBDS
      improved AP to values above the control and also nearly normalized phagocytosis.
      Chemotaxis markedly improved in cells treated with the low glucose-containing
      BBDS (Bic 20), containing high glucose concentrations (Bic 30). CONCLUSION: In
      comparison with conventional lactate-based dialysis solution-pH 5.2, bicarbonate
      based dialysis solution at low osmolality better preserves neutrophil functions
      that involve the cytoskeleton.

PMID- 7827188
TI  - Viscus perforation in peritoneal dialysis patients: diagnosis and outcome.
AB  - OBJECTIVE: To determine the incidence and outcome of spontaneous viscus
      perforation in peritoneal dialysis (PD) patients and which factors could
      facilitate early diagnosis. DESIGN: A retrospective chart review was done on all
      patients with viscus perforation and on a control group with peritonitis
      secondary to gram-negative organisms. SETTING: A tertiary care University
      Hospital Peritoneal Dialysis program. PATIENTS: All patients with surgically
      proven spontaneous viscus perforation from 1978 to June 1992 (n = 15). A group of
      control patients (n = 15) with gram-negative bacterial peritonitis was also
      reviewed for comparison. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Hospital
      days, patient survival after perforation, and return to peritoneal dialysis were
      the main outcomes measured. Peripheral white blood cell (WBC) count, PD fluid WBC
      count with differential, PD fluid cultures, radiologic information, and surgical
      intervention were also evaluated. Data were analyzed using the Mann-Whitney test
      to determine significant differences between the two groups. RESULTS: Viscus
      perforation occurred in 15 of the 431 patients on PD from 1978 to June 1992
      (3.5%). In comparison to the control group, patients with viscus perforation had
      a significantly higher peripheral WBC count (p = .016), a higher mean PD fluid
      WBC count (p = .006), and a higher mean percentage of polymorphonuclear cells in
      the PD effluent (p = .038). Multiple organisms on PD fluid cultures were noted in
      12 of 15 patients with perforation and in only 3 control patients.
      Pneumoperitoneum was seen on abdominal or chest radiograph or computerized
      tomographic (CT) scan in 10 of 15 patients with perforation and in only 1 of 15
      patients in the control group. All patients with viscus perforation required
      surgery and 6 expired. Only 1 death occurred in the control group. Only 1 of the
      9 patients surviving perforation was able to resume PD, in contrast to 13 of 14
      surviving control patients. CONCLUSION: We conclude that viscus perforation is
      associated with high morbidity, mortality, and technique failure. Diagnosis may
      be made by repeatedly searching for intraperitoneal free air on radiograph or CT
      scan in patients with persistently elevated peripheral and PD fluid WBC count,
      and for multiple organisms on PD fluid culture.

PMID- 7827189
TI  - Hormonal, blood pressure, and peritoneal transport response to short-term ACE
      inhibition.
AB  - OBJECTIVES: To evaluate the hormonal, blood pressure, and peritoneal transport
      effects of intraperitoneal enalaprilat and oral enalapril. DESIGN: A
      nonrandomized, nonblinded, prospective clinical trial was performed. SETTING: The
      study was conducted at the Clinical Research Unit at the Medical College of
      Virginia, a tertiary care center. PATIENTS: Six continuous ambulatory peritoneal
      dialysis (CAPD) patients with hypertension were enrolled in the study. All 6
      patients received intraperitoneal enalaprilat. Five of the patients also received
      oral enalapril. INTERVENTIONS: Hormonal, clinical, and transport parameters were
      investigated in patients given intraperitoneal enalaprilat and oral enalapril.
      Standardized 2-L exchanges were performed during a control period, following 2.5
      mg intraperitoneal enalaprilat and after a week of oral enalapril. Inulin, blood
      urea nitrogen (BUN) and creatinine clearances, and glucose absorption were
      determined during these exchanges. RESULTS: After intraperitoneal enalaprilat,
      both systolic and diastolic blood pressure significantly declined, reaching
      maximal decreases of -21.7 +/- 14.2% at 95 +/- 92 minutes, and of -23.3 +/- 15.4%
      at 105 +/- 105 minutes, respectively. Plasma angiotensin converting enzyme (ACE)
      activity was suppressed below detectable limits at four hours following
      intraperitoneal enalaprilat, and remained suppressed throughout all sampling time
      points following oral enalapril treatment. There was no significant change in
      drain volumes, glucose absorption, or BUN, creatinine, or inulin clearances,
      whether enalaprilat was administered intraperitoneally or enalapril orally.
      CONCLUSION: This study demonstrates that intraperitoneal administration of
      enalaprilat is a rapidly effective route of administration of this ACE inhibitor.
      There were no changes in peritoneal transport characteristics demonstrated.

PMID- 7827190
TI  - A 39-year-old man with loss of ultrafiltration.

PMID- 7827191
TI  - The risks of laparoscopic cholecystectomy in CAPD compared with hemodialysis
      patients: a study of ten patients.

PMID- 7827192
TI  - Stability of deferoxamine peritoneal dialysate solutions.

PMID- 7827193
TI  - Effect of edema on urea kinetic studies in peritoneal dialysis patients.

PMID- 7827194
TI  - Complications of peritoneal catheters placed by a single surgeon.

PMID- 7827195
TI  - The observed correlation between PCRN and KT/V is not a mathematical artifact?

PMID- 7827196
TI  - Dependence of normalized protein catabolic rate on KT/V in CAPD: not a
      mathematical artifact.

PMID- 7827197
TI  - Influence of instilled volume on the peritoneal equilibration test (PET)

PMID- 7827198
TI  - Lean body mass as an index of nutrition in CAPD patients.

PMID- 7827199
TI  - Neurotoxicity associated with intraperitoneal ceftazidime therapy in a CAPD
      patient.

PMID- 7827200
TI  - A retrospective analysis of catheter position and function in 91 CAPD patients.

PMID- 7827201
TI  - Literature. July-September 1994.

PMID- 7827202
TI  - Is the Durie and Salmon diagnostic classification system for plasma cell
      dyscrasias still the best choice? Application of three classification systems to
      a large population-based registry of paraproteinemia and multiple myeloma.
AB  - There are a number of systems for diagnosing multiple myeloma, myeloma variants
      and monoclonal gammopathy of undetermined significance. We compared three
      systems, those according to Durie and Salmon, to Kyle and Greipp, and to the
      British Columbia Cancer Agency, using material from a population-based registry
      of 847 patients with a paraproteinemia or multiple myeloma. Of these, 157
      underwent both bone marrow and X-ray examinations and were subsequently included
      in our analysis. The differences between the systems were small, even though in
      only 64% of the cases the diagnosis according to all three systems was identical.
      The system used by the British Columbia Cancer Agency turned out to be the
      shortest and easiest system reviewed here. We propose a more frequent application
      of this system instead of the more commonly used Durie and Salmon and Kyle and
      Greipp criteria.

PMID- 7827203
TI  - Characterization of bone marrow after transplantation by means of magnetic
      resonance.
AB  - Magnetic resonance (MR) has become a new tool for noninvasive characterization of
      bone marrow in patients with hematological disorders in the past few years.
      Experiences gained from 1H MR imaging and spectroscopic investigations in 48
      healthy volunteers and more than 130 patients with hematological disorders are
      reported and interpreted. Twenty-four of the patients underwent bone marrow
      transplantation (BMT) before the MR examinations. The findings in these studies
      provided noninvasive characterization and monitoring of vertebral marrow after
      BMT. Specifically, MR techniques were found to be suitable for studies of
      different aspects in physiological and pathological alterations of bone marrow:
      The water content within the marrow can be analyzed by chemical-shift selective
      imaging techniques with good spatial resolution. Spectroscopic methods also allow
      more sensitive quantification of the signal fractions, as well as separate
      evaluation of the relaxation times of water and lipids. Relaxometry might be
      useful to characterize the cellular and extracellular portions of water
      molecules. Furthermore, the distribution of the magnetic field within small
      volume elements of vertebral marrow can be measured. The field distribution is
      influenced by the trabecular density and the composition of the marrow. High
      amounts of hemosiderin in the marrow result in clearly broadened field
      distributions, demonstrated by increasing line widths in MR proton spectra.
      Magnetic resonance techniques can be used to assess not only the cellularity of
      the bone marrow, but also metabolic alterations in this compartment which result
      from cytotoxic treatment or immunological processes.

PMID- 7827204
TI  - Secondary acute myeloid leukemia with translocation (4;11) and MLL/AF4
      rearrangement in a 15-year-old boy treated for common acute lymphoblastic
      leukemia 11 years earlier.
AB  - Secondary acute myeloid leukemia occurring in a 15-year-old boy 11 years after
      initial treatment of a common lymphoblastic leukemia (c-ALL) is described.
      Initial complete remission was terminated after 4 years by an isolated testicular
      relapse, followed by first bone marrow relapse within 18 months. After he
      achieved remission again, an allogeneic bone marrow transplantation from his HLA
      identical brother was performed. Five years and 9 months later, the patient
      developed thrombocytopenia, leukopenia, and anemia, but bone marrow biopsies at
      this time demonstrated only myelofibrosis, with no blast cell population present.
      A polymerase chain reaction assay of a peripheral blood sample recognized the
      mRNA fusion region for the MLL/AF4 rearrangement, i.e., the molecular equivalent
      of the translocation (4;11)(q21,q23). Four weeks later, a blast cell population
      with AML-M1 morphology according to the FAB classification appeared in the bone
      marrow, and translocation (4;11) was detected by cytogenetics. Thus, secondary
      leukemias with chromosomal 11q23 rearrangement can develop after a long latency
      period and can be diagnosed earlier with the PCR technique.

PMID- 7827205
TI  - Case report of spontaneous remission of cytogenetic relapse of chronic
      myelogenous leukemia suggestive of progression to blast crisis after allogeneic
      bone marrow transplantation.
AB  - Detection of the chronic myelogenous leukemia (CML)-related marker, the bcr/abl m
      RNA transcript, in blood or bone marrow of patients with CML in hematologic
      remission after allogeneic bone marrow transplantation (allo-BMT) may be
      associated with the presence of minimal residual disease but does not uniformly
      predict hematologic relapse. In contrast, when there is cytogenetic reappearance
      of the Philadelphia (Ph1) translocation [t(9;22)(q34;q11)] along with additional
      cytogenetic abnormalities, especially more than 2 years after BMT, progression to
      hematologic relapse and acceleration of CML usually occur. An exception to this
      rule may be our patient, who was a 29-year old white woman diagnosed with Ph1
      positive CML by cytogenetics. She was initially treated with hydroxyurea. An allo
      BMT was performed 4 months after the diagnosis, while the patient was still in
      the first chronic phase of her disease, her HLA-identical brother serving as bone
      marrow (BM) donor. The conditioning regimen for BMT consisted of cytosine
      arabinoside, cyclophosphamide, total body irradiation, splenic irradiation, and
      intrathecal methotrexate. Graft-versus-host disease (GVHD) prophylaxis consisted
      of cyclosporin A and methotrexate. Her hospital course was unremarkable and
      without evidence of acute GVHD. Six months after transplantation, the patient had
      mild chronic GVHD and was treated with azathioprine and prednisone for 6 months.
      A year later, she recurred with mild chronic GVHD. She was treated with
      azathioprine alone for 5 months. Subsequently, she received cyclosporin A and
      prednisone for 8 months, with resolution of her symptoms. Serial BM cytogenetic
      studies showed normal male donor karyotypes 12 and 24 months after BMT. At 36,
      42, and 50 months after BMT, reappearance of the Ph1 was noted along with some
      cells with additional cytogenetic abnormalities, including t(6;14)(p21;q32). The
      breakpoint involvement of 14q32, the heavy chain Ig locus, in the new clone may
      be indicative of B-lymphoid lineage-based evolution. The abnormal clones
      disappeared 56 months from BMT and remained absent through 69 months after BMT.
      The patient has remained in hematologic remission during her entire post-BMT
      course. Clinically, she continues to do well without immunosuppressants at
      presently 69 months after BMT. The reappearance of the Ph1 chromosome could be
      associated with the immunosuppressive therapy given for chronic GVHD. This case
      supports the concept that immunologic mechanisms may be important in the
      eradication of CML after allo-BMT, and even cytogenetic evidence of blast crisis
      CML may spontaneously remit after allo-BMT.

PMID- 7827206
TI  - Accelerated phase of chronic myeloid leukemia presenting as pericadial
      extramedullary hematopoiesis.

PMID- 7827207
TI  - Syndrome of inappropriate secretion of antidiuretic hormone in patients with
      lymphoma-associated hemophagocytic syndrome.
AB  - We report three lymphoma patients in whom the syndrome of inappropriate secretion
      of antidiuretic hormone (SIADH) was observed during the course of lymphoma
      associated hemophagocytic syndrome (LAHS). The clinical course was devoid of any
      known mechanism for SIADH which could be attributable to lymphoma or
      antineoplastic treatment. Alternatively, high serum levels of interleukin-1 beta
      and tumor necrosis factor-alpha, which stimulate the secretion of antidiuretic
      hormone, may have contributed to the development of SIADH in our patients, who
      were receiving glucocorticoids. In conclusion, LAHS patients should be considered
      to be at high risk for SIADH.

PMID- 7827208
TI  - More on Munchhausen's syndrome in hematology: factitious limb edema in a patient
      with hemophilia.

PMID- 7827209
TI  - Microangiopathic hemolytic anemia and severe thrombocytopenia in Brucella
      infection.
AB  - A case of Brucella septicemia presenting at the onset as a severe
      microangiopathic hemolytic anemia with coexisting dramatic hemorrhagic syndrome
      (severe epistaxis, gross hematuria, and skin purpura) is reported. A hemogram
      showed severe thrombocytopenia, anemia, and leukopenia. Bone marrow morphology
      showed the typical features associated with Brucella infection: numerous
      histiocytes with signs of activation, multiple granulomata, giant cells, and
      hemophagocytosis. After appropriate antimicrobial therapy, the clinical and
      hematological status of the patient improved, and he is alive and well 1 year
      later with disappearance of all hematological abnormalities.

PMID- 7827210
TI  - Clinical heterogeneity of silent-gene b-thalassemia among Indians.
AB  - This paper describes six Indian families in which silent-gene beta-thalassemia
      was encountered by us in the past 2 years. This stresses the importance of globin
      chain synthesis in the diagnosis of beta-thalassemia. Of these six cases, five
      were diagnosed retrospectively when they had a homozygous beta-thalassemia
      offspring. The beta/alpha synthetic ratios ranged from 0.45 to 0.60. Four belong
      to group-I silent beta-thalassemia and two cases to group II. The severity of
      thalassemia major in the offspring of these silent carriers cannot be predicted.

PMID- 7827211
TI  - Psychiatric disease and the neurobiology of social behavior.

PMID- 7827212
TI  - 31phosphorus magnetic resonance spectroscopy of the frontal and parietal lobes in
      chronic schizophrenia.
AB  - In vivo 31Phosphorus magnetic resonance spectroscopic imaging (31P MRSI) was
      performed on 20 chronic schizophrenic patients and 16 normal controls to
      determine if there were specific changes in high energy phosphorus and
      phospholipid metabolism in the frontal lobes of schizophrenic patients.
      Phosphorous metabolites were assessed in each of the left and right frontal as
      well as the left and right parietal lobes. Frontal lobe phosphorous metabolites
      were also correlated with severity of psychiatric symptomatology as assessed by
      the Brief Psychiatric Rating Scale (BPRS). Schizophrenics demonstrated higher
      phosphodiesters (PDE) and lower phosphocreatine (PCr) in both the left and right
      frontal regions compared to controls. There was also lower left frontal inorganic
      phosphate (Pi) in the schizophrenic group. No group differences were noted in the
      left or right parietal regions. In addition, right frontal PDE and right frontal
      PCr were highly correlated with the hostility-suspiciousness and anxiety
      depression subscales of the BPRS. This study provides further support for altered
      frontal lobe phosphorous metabolism in schizophrenia.

PMID- 7827213
TI  - 24-hour lithium concentration in human brain studied by Li-7 magnetic resonance
      spectroscopy.
AB  - Brain and serum lithium concentrations were measured every second hour during a
      24-hr period following lithium intake, and again 48-hr later in two normal
      subjects in steady state lithium treatment receiving lithium carbonate (Priadel
      Synthelabo) once every evening. The brain-lithium concentration was measured by
      7Li magnetic resonance spectroscopy (MRS). The brain lithium level was found to
      undulate in a peak-trough pattern that followed the serum lithium profile,
      although in an attenuated form. The brain/serum lithium concentration ratio
      varied considerably during the 48-hr period, ranging from 0.5 to 1.3, but the
      ratio was independent of the serum-lithium concentration. The median half-life
      for lithium was 28 hr in the brain, and 16 hr in serum. The brain lithium
      concentration in the morning was about 75% of the clinically relevant standard 12
      hr serum lithium concentration. The finding that brain lithium undulates during
      the day means that MRS measurements of brain lithium can only be compared if
      carried out under standard conditions that include a fixed interval following
      lithium intake and an identical treatment regimen.

PMID- 7827214
TI  - Viral antibodies in recent onset, nonorganic psychoses: correspondence with
      symptomatic severity.
AB  - A parallel of generalized viral infection with psychiatric symptoms has been
      reported in nonorganic psychotic disorders. The patients concerned had been ill
      for long periods and some of them had been readmitted. In order to determine the
      presence of viral infection at the very onset of the psychosis, antibodies in
      blood and cerebrospinal fluid (CSF) to six viruses [cytomegalovirus (CMV), herpes
      simplex (HSV) Type 1, mumps, measles, varicella zoster virus (VZV), and Japanese
      encephalitis virus (JEV)] were assayed in 35 psychotic patients [14
      schizophrenics; 13 manic patients; and 8 patients with psychosis not otherwise
      specified (NOS)] within 1 month of onset of illness. Ten (28.6%) patients had a
      diagnostic (fourfold) change in the antibody titer in the paired serum and/or CSF
      samples (drawn at 2-week intervals) and another 10 had high titers (above 2 SDs
      from the mean in 35 control subjects). The striking temporal correlation with the
      initial severity and resolution of psychopathology by 2 weeks on the Brief
      Psychiatric Rating Scale (BPRS) suggests a causally significant, currently active
      viral infection in these 20 cases.

PMID- 7827215
TI  - Concordance of smooth pursuit and saccadic measures in normal monozygotic twin
      pairs.
AB  - Although the range of normal ocular motor performance is broad, little is known
      about the sources of variability. Genetic transmission of eye movement deficits
      has been described but such possible control of normal function has been little
      investigated. Characteristics of smooth pursuit and saccades can be examined for
      the degree of concordance in related individuals. In this pilot study, we studied
      saccades and pursuit in eight monozygotic (MZ) twin pairs. The statistical
      analysis of the data used the intraclass correlation of MZ twins (rMZ) to
      estimate what fraction the covariance of the twin pairs was of the population
      variance. All saccadic measures showed significant MZ correlations (p < 0.05).
      Smooth pursuit gains were even more highly correlated (p < 0.001). These results
      indicate considerable similarity within pairs of twins, particularly for
      horizontal smooth pursuit, and suggest that larger studies on monozygotic and
      dizygotic twins would be desirable, to help separate out the relative
      contributions of environmental and genetic factors.

PMID- 7827216
TI  - P300 responses to novel auditory stimuli in hospitalized schizophrenic patients.
AB  - The authors studied the scalp topography of P300 responses to novel auditory
      stimuli and its relationship to negative symptoms in medication-free hospitalized
      schizophrenic patients. Schizophrenics (n = 12), patients with major mood
      disorders (n = 13), and 17 non-ill controls (all men) responded to rare target
      tones while ignoring background tones and rare novel stimuli. P300 responses were
      identified from plots of global field power (GFP), a measure of potential
      variability over the entire electrode set. Multivariate analysis revealed that
      P300 responses to novel stimuli were faster (p < 0.003), larger (p < 0.001), and
      distributed more centrally than parietally (p < 0.001) than those to targets, but
      this central augmentation was significantly (p < 0.04) less in schizophrenics.
      Compared to controls, P300 amplitude (p < 0.05) and GFP (p < 0.02) after novel
      stimuli were reduced relative to target responses in schizophrenics. Negative
      symptoms were inversely correlated with P300 amplitude (P = 0.013) and GFP (p <
      0.04) across conditions and with P300 GFP in the novel condition (p = 0.01), but
      did not predict topography of responses to novel stimuli. The findings were
      consistent with but not conclusive evidence of prefrontal impairment in the
      schizophrenics subjects. Methodological issues and conflicts with other reports
      are discussed.

PMID- 7827217
TI  - Thyrotropin response to TRH stimulation in depressed patients with autoimmune
      thyroiditis.
AB  - Two thyroid axis findings are often reported in depressed patients: autoimmune
      thyroiditis and abnormal thyrotropin (thyroid stimulating hormone, TSH) responses
      to thyrotropin-releasing hormone (TRH). The TSH response to TRH can be
      exaggerated, suggesting subclinical hypothyroidism; it can alternatively be
      blunted, for reasons poorly understood. We selected 28 women who had been found
      to have major depression for TRH testing. Fifteen patients had autoimmune
      thyroiditis and 13 had diffuse nontoxic goiter. The endocrinological diagnoses
      were verified by fine-needle aspiration biopsy and cytological assessment.
      Patients with overt hypothyroidism and hyperthyroidism were excluded from the
      study. There were no differences between the two groups in total triiodthyronine
      and thyroxine plasma levels or severity of depression. In the autoimmune group,
      basal TSH and Dmax TSH tended to be higher (p < 0.1); peak TSH was significantly
      higher (p < 0.05), suggesting that the prevalence of subclinical hypothyroidism
      was also higher. Blunted TSH responses were found about as often in one group as
      the other.

PMID- 7827218
TI  - Autonomic function in panic disorder: cardiorespiratory and plasma catecholamine
      responsivity to multiple challenges of the autonomic nervous system.
AB  - Panic disorder has been widely hypothesized to be associated with dysfunction of
      the autonomic nervous system. In this study, 24 patients with panic disorder and
      26 healthy control subjects took part in a broad battery of autonomic function
      tests, each designed to stress the autonomic nervous system in a particular
      fashion. Testing consisted of postural challenge, isometric exercise, cold
      pressor, and Valsalva maneuver. Dependent measures included heart rate, vagal
      tone, blood pressure, respiratory frequency, end-tidal CO2 levels, and plasma
      norepinephrine and epinephrine levels. The testing procedures reliably produced
      changes in autonomic output in the expected directions, but patients with panic
      disorder were not found to differ from healthy controls in their
      cardiorespiratory or plasma catecholaminergic responses. This pattern of normal
      autonomic responsivity in the patients with panic disorder was evident across
      multiple test conditions with varying autonomic demand characteristics, thereby
      supporting the integrity of autonomic regulatory systems in this illness. These
      data run counter to a simple notion of autonomic dysfunction in panic disorder.

PMID- 7827219
TI  - Lack of insight: its status within schizophrenic psychopathology.

PMID- 7827220
TI  - A likely in vivo probe of human circadian timing system function using PET.

PMID- 7827221
TI  - Famous names in toxicology. Doctor Quicksilver, alias Thomas Dover.

PMID- 7827222
TI  - Selective serotonin reuptake inhibitors: adverse effects, toxicity and
      interactions.

PMID- 7827223
TI  - Omeprazole: short- and long-term safety.

PMID- 7827224
TI  - Anticoagulants and skin necrosis.

PMID- 7827225
TI  - Qualitative study of collagenous and noncollagenous glycoproteins of the human
      healthy keratinized mucosa surrounding implants.
AB  - The purpose of this study was to analyse the distribution of interstitial
      collagenous and noncollagenous glycoproteins of keratinized mucosa surrounding
      successful endosseous implants. Biopsies were incubated with highly purified
      antibodies against types I, III, IV collagen, laminin and fibronectin and
      routinely observed by immunofluorescence staining. Whereas no significative
      difference in the distribution of collagenous components was observed in
      comparison with healthy human gingiva, the collagen fibers of the connective
      tissue attachment ran parallel to the long axis of the implant. In 50% of the
      biopsies the gingival connective tissue underlying the junctional epithelium was
      rich in inflammatory cells and poor in collagenous components. However, the
      increased staining of type III collagen and the intense presence of fibronectin
      in this area reflect the very important remodeling ability of the local
      keratinized mucosa.

PMID- 7827226
TI  - Membrane permeability is unnecessary for guided generation of new bone. An
      experimental study in the rabbit.
AB  - The aim of this investigation was to test the hypothesis that membrane
      permeability is necessary in bone formation using the principle of guided tissue
      regeneration. On the forehead of 8 rabbits, titanium test cylinders were anchored
      in the calvaria. These cylinders were either covered by an expanded
      polytetrafluoroethylene (ePTFE) membrane generating a chamber for bone formation
      or they were sealed off by cast titanium. The implanted cylinders were covered by
      resuturing the periosteum and the cutaneous flap. After 8 months of healing, new
      bone had formed in all cylinders in all animals irrespective of whether the
      chamber for bone formation was sealed off by cast titanium or the ePTFE membrane.
      Based on these results, we conclude that permeability of the membrane is not
      necessary in the guided generation of new bone.

PMID- 7827227
TI  - Predictable crestal bone remodelling around two porous-coated titanium alloy
      dental implant designs. A radiographic study in dogs.
AB  - We have previously suggested that altering the height of the porous-coat segment
      of a partially porous-coated TiAl6V4 endosseous dental implant would affect the
      degree of crestal bone loss occurring during implant function by changing the
      patterns of stress transfer. This conclusion arose from the analysis of data from
      several different experiments and lacked a direct intra-animal comparison. In the
      present study we have compared two implant designs varying only in the extent to
      which they were porous-coated. With one design (type A) the coronal 1.8 mm of the
      implant root had a machined surface while the remainder of its length was porous
      coated with TiAl6V4 beads. The other design (type B) had all but the coronal-most
      0.75 mm porous-coated. Two implants of each type were placed in each of 4 dogs
      and the sites allowed to heal for 4 weeks before re-entry and prosthesis
      attachment. Monthly the implant-supported bridges were removed and radiographs
      exposed of each implant using a special film holder connected separately to each
      implant. These radiographs were analyzed for crestal bone loss using both direct
      visual and computer-assisted techniques. The results showed that bone remodelled
      to the machined surface-to-porous coat junction for type B implants and achieved
      a steady state by 12 weeks of function, whereas a longer time was required to
      achieve this state with type A implants. Significantly more bone loss occurred
      with the type A design, and this difference was detectable as early as after the
      first month of function.

PMID- 7827228
TI  - Fixed implant-supported prostheses in the edentulous maxilla. A five-year follow
      up report.
AB  - Seventy-six patients were consecutively treated with fixed prostheses supported
      by osseointegrated implants in the edentulous maxilla and followed up for 5
      years. The mean bone quality and resorption indices were 3.1 and 2.7 at the time
      of implant placement, respectively. Altogether, 449 standard Branemark implants
      were placed. Two patients resumed to complete dentures, and the cumulative
      implant and prosthesis survival rates were 92.1% and 95.9% for 5 years,
      respectively. The mean marginal bone level was 0.6 mm below the reference point
      at the time of placement and 1.2 mm below the same point 5 years later. Speech
      problems was the most frequent complaint during the first year of function, while
      resin fractures caused most adjustments during the follow-up period. No implant,
      abutment or gold alloy screws were found to be fractured, and only 4 patients had
      their prostheses re-tightened due to loose gold alloy screws.

PMID- 7827229
TI  - Inhibition of peri-implant bone loss with the nonsteroidal anti-inflammatory drug
      flurbiprofen in beagle dogs. A preliminary study.
AB  - There is increasing interest in how pathways of tissue destruction around dental
      implants are similar as for teeth and how these pathways can be modulated to slow
      loss of supporting bone. The purposes of this study were to develop a short-term
      animal model to study the effect of the nonsteroidal anti-inflammatory drug
      flurbiprofen, on slowing the rate of induced peri-implant bone resorption. A
      total of 20 cylindrical titanium implants were placed in 2 beagle dogs using a
      low-trauma surgical technique. During the 3-month healing period without
      functional loading of the implants, daily oral hygiene was performed to maintain
      a Gingival Index of 0 to 0.5. At completion of the healing period, a baseline
      evaluation was performed which included the uptake of the bone-seeking
      radiopharmaceutical (BSRU) 99mtechnetium-tin-diphosphonate (99mTc-Sn-MDP) in peri
      implant bone and standardized radiographs. Peri-implantitis was induced with 4-0
      silk ligatures, cessation of oral hygiene and soft diet. One beagle was given
      0.02 mg/kg of flurbiprofen by mouth; the other received a placebo. BSRU and
      radiographic height of bone were remeasured to calculate the rate of bone loss
      during the 60-day treatment period. The percent rate of bone loss during the
      study period was calculated from the radiographs using a computer-assisted
      method. The radiopharmaceutical uptake for the flurbiprofen-treated implants
      remained unchanged. However, BSRU for placebo-treated implants was significantly
      increased from baseline.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7827230
TI  - Immediate transmucosal implants using the principle of guided tissue
      regeneration. I. Rationale, clinical procedures and 30-month results.
AB  - The installation of implants directly into extraction sockets offers considerable
      advantages over other treatment modalities for both practitioners and patients.
      Usually, immediate implants are placed and subsequently covered by mucosa
      allowing a submerged healing mode. This report presents the rationale, clinical
      procedures and results for immediate transmucosal implants. Following an
      intracrevicular incision and flap elevation, the tooth to be extracted is
      carefully luxated by means of small elevators to preserve the entire bony housing
      of the tooth. A titanium plasma-sprayed implant (ITI Bonefit) is then installed
      at the bottom or in the wall of the extraction socket. An expanded
      polytetrafluoroethylene barrier membrane (Gore-Tex GTAM) is tightly adapted
      around the implant post and over the bony margins of the alveolus. The flaps are
      then replaced, adapted around the neck of the implant and sutured. During
      nonsubmerged, transmucosal healing of the site, meticulous plaque control is
      performed by mechanical and chemical means. Membranes are removed after 5-7
      months. Since infection was prevented, the implants obtained stability, healthy
      peri-implant mucosal tissues were observed and missing bone in the alveoli
      regenerated. Of 21 transmucosal implants placed into fresh extraction sockets, 20
      yielded complete bone fill and coverage of the entire plasma-coated implants
      surface at the time of membrane removal. This documentation suggests that the
      immediate nonsubmerged installation of an implant into an extraction socket is a
      predictable treatment modality with good long-term prognosis.

PMID- 7827231
TI  - ITI implants in combination with bone grafts: design and biomechanical aspects.
AB  - In this article we describe the implantation of ITI implants in combination with
      bone grafts. Two different cases were considered: the augmentation of an atrophic
      maxilla or mandible where the transplant was fixed by means of ITI implants and
      the implantation into free transplants fixed by means of the THORP reconstruction
      plate system. These indications require 2-stage procedures with submerged
      implants and transplants during the healing period. For this new applications,
      standard ITI implants were combined with specially developed new transgingival
      units of high manufacturing precision. The new design resulted in a maximum
      tightening moment of 4.0 N.m versus 1.25 N.m achievable with a conventional 2-mm
      screw. Dynamic testing showed that, for the range of tightening moments of 0.25
      N.m up to 1.0 N.m, the loosening moment after 2,000,000 cycles remained
      approximately 10% above the tightening moment. For the clinical application a
      tightening moment of 0.35-0.5 N.m is recommended. The special design and the high
      precision of the extension parts results in a tight adaptation between the
      primary implant and the extension parts, which may be important for
      microbiological reasons.

PMID- 7827232
TI  - Histological evidence of osseointegration 4 years after implantation. A case
      report.
AB  - Histological examinations of clinically successful dental implants are very rare
      in the literature. This article presents a clinical case where an ITI hollow
      cylinder titanium implant type F (red mark, 16 mm) had to be removed
      simultaneously with the resection of a squamous cell carcinoma of the lower jaw.
      The duration of functional loading of the implant was 49 months. The fixture was
      situated at the margin of the tissue to be resected during tumor surgery and
      could therefore be prepared as a histological specimen independent of the
      tumorous tissue. In the sections obtained, close contact of alveolar bone to the
      implant surface was clearly visible. Together with the clinical success of the
      implant, criteria of osseointegration seems to have been matched. This
      observation represents the longest histological survey of a clinically successful
      fixture of this implant system.

PMID- 7827233
TI  - The use of a new bioresorbable barrier for guided bone regeneration in connection
      with implant installation. Case reports.
AB  - This report presents 4 cases with 6 implant exposures after the installation of
      Branemark System implants which called for treatment applying the guided bone
      regeneration technique. A bioresorbable barrier (GUIDOR Matrix Barrier) was used
      to cover the defects, 4 defects with and 2 without the support of autologous bone
      chips. Complete bone filling was found in 4 (2 without and 2 with bone chips) and
      partial filling in 2 (with bone chips) of the treated defects, as registered at
      the abutment connection 6-7 months after surgery. Besides its ability to serve as
      a barrier for guided bone regeneration, it was found that the matrix barrier had
      the following properties; biocompatibility observed as uneventful tissue healing,
      malleability facilitating the clinical handling and ability to be resorbed within
      6 to 7 months, as evaluated by clinical inspection. The observations of the
      present case reports indicate that the tested barrier may be used for guided bone
      regeneration in connection with implant installation. It is advisable, however,
      to use a supporting material to prevent barrier collapse, although bone
      regeneration can be achieved in certain situations without such material if the
      defect morphology is favourable.

PMID- 7827234
TI  - Clinical and radiographical features of submerged and nonsubmerged titanium
      implants.
AB  - A clinical and radiographical study was performed to evaluate whether initial
      submergence of titanium fixtures is an obligate treatment measure for the
      establishment of proper bone anchorage when implants a.m. Branemark are used. The
      sample was comprised of 11 subjects with edentulous mandibles. A split-mouth
      design was employed; in the right mandibular quadrant a traditional 2-step
      procedure for fixture installation and abutment connection was utilized, while in
      the left quadrant a 1-step procedure was carried out, i.e., fixtures were placed
      and abutments were connected in one and the same session. Three to 4 months after
      fixture installation, fixed bridgeworks were fabricated and rigidly connected to
      the implants. Clinical examinations (including probing pocket depth, bleeding on
      probing and implant stability test) were performed after 12 and 18 months.
      Radiographs were taken following insertion of the bridges and at the 12- and 18
      month re-examinations. The probing pocket depth, the bleeding on probing, the
      implant stability and the radiographic determinations were similar for the 2
      groups of treatment alternatives. This indicates that titanium fixtures a.m.
      Branemark can be properly anchored (osseointegrated) in mandibular bone and
      successfully used for bridge retention also when a 1-step procedure is used for
      implant installation.

PMID- 7827235
TI  - Menopausal estrogen and estrogen-progestin replacement therapy and risk of breast
      cancer (United States).
AB  - This study examines the relationship between menopausal estrogen and estrogen
      progestin replacement therapy and risk of breast cancer, focusing on whether
      associations differ according to whether the tumors are in situ or invasive. Data
      are from a prospective study conducted 1980-89 on 49,017 selected participants in
      the Breast Cancer Detection Demonstration Project, a five-year screening program
      conducted between 1973 and 1980 in the United States. Overall, the rate ratio for
      estrogen-only use compared with no-hormone use was 1.0, and that for the estrogen
      progestin combination was 1.2 (95 percent confidence interval [CI] = 1.0-1.6).
      However, the associations differed according to whether the tumors were in situ
      or invasive. The rate ratios of in situ breast cancer associated with use of
      estrogens alone and the combination regimen were 1.4 (CI = 1.0-2.0) and 2.3 (CI =
      1.3-3.9), respectively. Duration of estrogen-only use also was associated with
      risk of in situ tumors, with users for 10 or more years at twice the risk of
      nonusers (P-value for trend test = 0.02). Duration of use was not associated with
      risk of invasive cancer. Our results are consistent with the hypothesis that
      hormone replacement therapy is related to earlier-stage breast cancer; however,
      the possibility that the results reflect increased breast cancer surveillance
      among those taking hormones cannot be ruled out.

PMID- 7827236
TI  - Risk of breast cancer in relation to blood lipids: a prospective study of 31,209
      Norwegian women.
AB  - In this prospective study, the relationship between blood lipids and breast
      cancer risk was examined. Between 1977 and 1983, 31,209 Norwegian women, 20 to 54
      years of age, attended a health screening carried out by the Norwegian National
      Health Screening Services. The screening consisted of a questionnaire,
      anthropometric measurements, and nonfasting blood drawn for analysis of total
      serum cholesterol (TC), triglyceride (TG), and high density lipoprotein (HDL)
      cholesterol. Low density lipoprotein (LDL) cholesterol was calculated by the
      Friedewald's formula. During the seven to 13 years of follow-up, 302 breast
      cancer cases were identified by linkage to the Norwegian Cancer Registry. After
      adjustment for some of the known risk factors of breast cancer, the relative risk
      of women in the highest quartile of TC compared with women in the lowest quartile
      was 0.87 (95 percent confidence interval [CI] = 0.61-1.23). The corresponding
      relative risks and CIs were 0.82 (CI = 0.58-1.16) for TG, 1.02 (CI = 0.73-1.42)
      for HDL, and 0.93 (CI = 0.67-1.29) for LDL. No association between breast cancer
      risk and blood lipids was found in the total population, nor when the data were
      divided into those diagnosed before or after the age of 50 as a dividing line
      between pre- and postmenopausal diagnosis.

PMID- 7827237
TI  - Epidemiologic correlates of breast cancer laterality (Sweden).
AB  - Breast cancer laterality was studied in relation to age in 80,784 cases of
      invasive and 3,835 cases of pre-invasive breast cancer in women and 548 cases of
      invasive breast cancer in men reported to the Swedish Cancer Registry, 1970-89.
      In a subset of 11,274 women with invasive disease, data on parity were available
      through the Swedish Fertility Registry. Laterality also was evaluated in relation
      to age and reproductive variables in 3,986 cases from an international study from
      the 1960s. The overall incidence of pre-invasive and invasive cancer was higher
      in the left than in the right breast among both women and men. The excess
      incidence of invasive cancer in the left breast was evident only after the age of
      45 years in women; a similar phenomenon may exist with pre-invasive disease in
      women and in men. The age-dependent laterality pattern did not appear to be
      confounded by menopausal status. Among women younger than 45 years, nulliparity,
      right handedness, and late age at menarche was associated with a somewhat higher
      incidence of cancer in the right breast. The laterality findings are likely to be
      due to factors operating early in the carcinogenic process, perhaps at the pre
      initiation stage.

PMID- 7827238
TI  - Bladder cancer: epidemiology and risk factors in Bulawayo, Zimbabwe.
AB  - The incidence of bladder cancer, and the importance of some selected risk factors
      in its etiology, were estimated from the data collected in the cancer registry of
      Bulawayo, Zimbabwe, during the period 1963-77. Cancer cases were interviewed with
      a standard questionnaire, and more than 70 percent of these were complete.
      Incidence rates in the urban population of Bulawayo in the first 10-year period
      were relatively high, with age standardized rates of 17.9 per 100,000 in men and
      9.5 in women. Risk-factor distribution was compared in 680 bladder cancer cases
      (494 males, 186 females) and a control group comprising other cases with non
      tobacco-related cancers (8,201). Seventy-one percent of bladder cancer cases were
      squamous cell carcinomas. The presence of schistosomiasis, evaluated from past
      history of bilharzia or hematuria, was associated with a significantly increased
      risk of bladder cancer in both genders (odds ratio [OR] = 3.9 for men, 5.7 for
      women), a result reflected in the differing risk by province of residence, which
      correlated with the prevalence of infection among cancer cases. The proportion of
      bladder cancer attributable to schistosomiasis was estimated to be 28 percent.
      Social status, as reflected by education level, also influenced risk (ORs for
      literate cf illiterate males = 0.6), but tobacco smoking in men had no effect on
      the risk of squamous cell tumors. For transitional cell carcinomas or
      adenocarcinomas, there was a nonsignificant increased risk of 2.0 in the highest
      smoking categories (15 g of tobacco per day), compared with non smokers.

PMID- 7827239
TI  - Reduced risk of breast and endometrial cancer among women with hip fractures
      (Sweden).
AB  - To test the hypothesis that osteoporosis, which results partly from long-term
      estrogen deficiency, is associated with a lowered risk of breast and endometrial
      cancer, a population-based cohort study was performed in Sweden. Some 18,000
      women were followed through record-linkages after a first hip fracture, on
      average for almost six years, to ascertain the incidence of breast and
      endometrial cancer. Expected numbers were derived from the general population.
      Overall, 253 cases of breast cancer were observed cf 300 expected (standardized
      incidence ratio [SIR] = 0.84; 95 percent confidence interval [CI] = 0.74-0.95).
      Forty-eight cases of endometrial cancer were found cf 55 expected (SIR = 0.87, CI
      = 0.54-1.16). There was no clearcut pattern of breast cancer risk by age at
      diagnosis of hip fracture, follow-up time, or calendar period. Our results are
      consistent with the a priori hypothesis that long-term estrogen deficiency is
      associated with a reduced risk of developing breast cancer as well as endometrial
      cancer.

PMID- 7827240
TI  - Multiple myeloma among blacks and whites in the United States: the role of
      chronic antigenic stimulation.
AB  - Multiple myeloma (MM) is twice as common among Blacks than Whites in the United
      States. The reasons for this racial disparity are unknown, and the etiology of
      this cancer, in general, is poorly understood. Repeated or chronic antigenic
      stimulation (CAS) of the immune system has been suggested as a risk factor.
      Previous case-control studies have reported inconsistent CAS associations based
      on evaluations of individual and biologic categories of medical conditions.
      Interview data from 573 cases and 2,131 population-based controls were used to
      investigate further the CAS hypothesis using an immunologically based approach,
      and to determine whether CAS accounts for the excess of myeloma among Blacks.
      Over 50 medical conditions were grouped into biologically and immunologically
      related categories, and B-cell- and T-cell-mediated response groups. Except for
      urinary tract infections among Black men (odds ratio [OR] = 2.0), no
      significantly increased risks of MM were observed. However, there was a
      suggestion of increased risk among Blacks with an increased exposure to
      anaphylactic conditions. Analysis by immunoglobulin type revealed significantly
      elevated risks of IgG myeloma with eczema (OR = 2.1), the biologic category
      'allergic conditions' (OR = 1.6), and the immunologic category 'anaphylaxis
      response' (OR = 1.6) among Whites, with Blacks having slightly lower risks. Our
      findings do not support a causal relationship between CAS and MM, nor do they
      explain the higher incidence among Blacks.

PMID- 7827241
TI  - Dietary lactose intake, lactose intolerance, and the risk of epithelial ovarian
      cancer in southern Ontario (Canada).
AB  - A case-control study of dietary factors and cancer of the ovary was conducted
      during 1989-92 in metropolitan Toronto and surrounding areas of southern Ontario,
      Canada. Four hundred and fifty women aged 35-79 years, with newly diagnosed,
      histologically verified, primary epithelial ovarian-cancer were interviewed
      concerning reproduction and diet. Over the same period, 564 randomly-selected
      population controls, frequency-matched to the cases within three 15-year age
      groups, also were interviewed. From information obtained by quantitative diet
      history, average daily macro- and micronutrient intake values were calculated
      through use of the United States Department of Agriculture Food Composition
      Databank, which was extended and modified for Canadian items and recipes.
      Analysis was performed with continuous, unconditional logistic-regression
      methods, adjusting for age at interview, number of full-term pregnancies, total
      duration of oral contraceptive use, and total daily caloric intake. Neither
      reported history of lactose intolerance, nor average daily consumption of lactose
      or free galactose, were found to be associated with risk of ovarian cancer.
      Lactose intake or intolerance did not appear to modify the protective effects of
      parity and oral contraceptive use. Nevertheless, other studies suggest that
      ovarian galactose metabolism still may have a relationship with risk of ovarian
      cancer, though more evidence is needed.

PMID- 7827242
TI  - Physical activity and the risk of prostate and testicular cancer: a cohort study
      of 53,000 Norwegian men.
AB  - The associations between recreational and occupational physical activity and the
      subsequent risk of prostate and testicular cancer were examined in a population
      based cohort study of 53,242 men in Norway. Age at study entry was 19 to 50
      years. Information on physical activity was based on questionnaire responses and
      a brief clinical examination. A total of 220 prostate and 47 testicular cancer
      cases were recorded in the Cancer Registry of Norway during a mean follow-up time
      of 16.3 years. We found a nonsignificant, reduced, adjusted relative risk (RR) of
      prostate cancer with increased level of physical activity at work and among those
      men with the greatest recreational physical activity. When occupational and
      recreational physical activity were combined, a reduced adjusted risk of prostate
      cancer was observed among men who walked during occupational hours and performed
      either moderate recreational activity (RR = 0.61, 95 percent confidence interval
      [CI] = 0.36 to 1.01) or regular recreational training (RR = 0.45, CI = 0.20 to
      1.01) relative to sedentary men (test for trend, P = 0.03). Physically active men
      who were older than 60 years of age at diagnosis showed a reduced adjusted RR of
      borderline significance, while no association was observed for younger men. No
      evidence was found for any association between physical activity and testicular
      cancer regardless of physical activity at work and recreation.

PMID- 7827243
TI  - Age and risk factors for colon cancer (United States and Australia): are there
      implications for understanding differences in case-control and cohort studies?
AB  - Data from two population-based case-control studies were used to investigate the
      effect of age on colon cancer risk. Dietary intake data were assessed from a
      study conducted in Utah (United States) between 1979 and 1983; reproductive data
      were assessed from a study conducted in Adelaide (Australia) between 1979 and
      1980. Data from both studies were assessed for their impact on those less than 65
      years of age and those 65 or more years of age. Intake of energy, fat, and
      protein had a greater impact on risk among older men than among younger men. Risk
      estimates for the upper quartile of intake relative to the lowest quartile of
      intake were 8.5 (95 percent confidence interval [CI] = 1.7-43.0) for energy, 8.2
      (CI = 1.6-41.3) for protein, and 7.2 (CI = 1.6-31.4) for total fat for older men,
      while comparable risk estimates were 2.4 (CI = 0.6-9.1) for energy, 3.0 (CI = 0.7
      13.6) for protein, and 1.9 (CI = 0.5-7.1) for total fat among younger men.
      Similar trends were seen for older women for energy and protein. beta-carotene
      decreased colon cancer risk among younger men (odds ratio [OR] = 0.4, CI = 0.1
      1.2) and women (OR = 0.1, CI = 0.1-0.5), although not among older men (OR = 1.2,
      CI = 0.3-4.9) and women (OR = 1.9, CI = 0.6-64). Calcium decreased risk of colon
      cancer among older men (OR = 0.1, CI = < 0.1-0.8) and younger women (OR = 0.2, CI
      = < 0.1-0.7).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7827244
TI  - Melanoma and sunburn.
AB  - A computer-aided search identified 16 case-control studies which specifically
      assessed sunburn as a risk factor for cutaneous malignant melanoma. Using
      unadjusted estimates, a history of sunburn was associated with significantly
      increased risk of melanoma in all but one study. Four studies were defined as
      core studies after assessment of study quality; however, only two of these had
      sufficiently similar definitions of sunburn to allow pooling of results. Using
      pooled data, the risk of melanoma in those ever sunburned was 2.0 (95 percent
      confidence interval [CI] = 1.6-2.6), while the highest category of sunburn
      exposure had a risk of 3.7 (CI = 2.5-5.4). The suggestion that sunburns in
      childhood carry greater risk of melanoma cannot be supported by pooled analysis.
      This review demonstrated considerable variation in design and method among the
      studies, and identified sources of bias which prevented a pooled analysis using
      all available data. The need for strong epidemiologic evidence relating sunburn
      to melanoma, particularly in childhood, is of prime importance, since avoidance
      of sunburn is one of the few potential means of primary prevention of melanoma.

PMID- 7827245
TI  - Rising incidence rate of esophageal adenocarcinoma and use of pharmaceutical
      agents that relax the lower esophageal sphincter (United States).
AB  - Primary adenocarcinoma of the esophagus, previously considered a rare neoplasm,
      has shown a dramatic increase in its incidence rate among White men in the United
      States since 1970. The reason for this increase is unknown. Since the presence of
      Barrett's esophagus is essential for the development of most esophageal
      adenocarcinomas, the increasing incidence of esophageal adenocarcinoma may be
      related to an increasing prevalence of Barrett's esophagus, and its precursor,
      gastroesophageal reflux. An association between this increasing incidence and an
      increasing use of pharmaceutical agents that relax the lower esophageal sphincter
      is proposed. The data on the dollar amount and approximate quantity in milligrams
      purchased per capita through retail pharmacies and hospitals in the United States
      from 1957 to 1986 are presented for four categories of such agents. An upward
      trend is observed for all four categories.

PMID- 7827246
TI  - Power lines, viruses, and childhood leukemia.

PMID- 7827247
TI  - Cancer in Swedish railway workers.

PMID- 7827248
TI  - Melanoma incidence in Connecticut.

PMID- 7827249
TI  - Myocardial ischemia, infarction, and failure: an odyssey.

PMID- 7827250
TI  - Structure and function of the fish cardiac ventricle: flexibility and
      limitations.
AB  - Fishes show the highest diversity among vertebrates. Defined differences in
      ventricular myoarchitecture exist in fish. There are two main types of cardiac
      ventricle in fish: a spongy type and a mixed type. In the spongy ventricle, the
      muscle trabeculae form a sponge-like network, the spongiosa. In the mixed
      ventricle, one or more superficial layers of compact tissue (compacta) enclose an
      inner spongiosa. The spongiosa and compacta are respectively associated with a
      lacunary and a vascularized supply of blood. Interspecies differences exist in
      the proportion of compacta and the extent of vascularization. Here the mechanical
      limits and flexibility of the different types of ventricular organization are
      examined. The spongy type (found only in teleosts) seems to be particularly
      suitable for performing volume work. An example is the icefish heart. The main
      characteristics of this fish are the absence of hemoglobin in the blood and the
      very large volume of blood. The cardiac ventricle of the icefish is characterized
      by a cardiomegaly of the spongy type with myocardial pseudohypertrophy. It
      functions as a specialized volume pump which moves large stroke volumes at a low
      heart rate, but is not able to produce high pressures. The most active teleosts
      have mixed heart ventricles with different thicknesses of compacta. The presence
      of compacta gives these types of heart the potential to act as pressure pumps:
      they move small volumes at a relatively high rate and high pressure. The tuna
      heart is an extreme example of the mixed type. It has the highest relative mass
      and proportion of compacta (40-70%) among fishes.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7827251
TI  - Coronary hemodynamics in elasmobranchs and teleosts.
AB  - Until recently, direct measurements of coronary blood flow in fishes had not been
      made. This review presents and compares in vivo measurements of coronary flow
      recorded from the school shark, Galeorhinus australis, and the coho salmon,
      Oncorhynchus kisutch. In both species, the coronary blood flow was phasic and
      strongly influenced by the cardiac cycle. Coronary blood flow in the school shark
      was more severely compromised by the cardiac cycle with a short retrograde flow
      occurring during systole. In the coho salmon, there was an anterograde coronary
      blood flow throughout the cardiac cycle. Differences in coronary hemodynamics are
      discussed in relation to differences in the myoarchitecture of the school shark
      and coho salmon hearts. The regulation of coronary blood flow through changes in
      vascular resistance (vasoactivity of the coronary vessels) is also discussed.

PMID- 7827252
TI  - The crocodilian heart and central hemodynamics.
AB  - The crocodilian heart is completely divided into two atria and two ventricles,
      resembling the arrangement in birds and mammals. However, in addition to the
      systemic aorta (right aorta, RAo) which emerges from the left ventricle, there is
      a second aorta (left aorta, LAo) that leaves the right ventricle beside the
      common pulmonary artery. The two aortae communicate immediately outside the
      valves through a small aperture, the foramen of Panizza. During diastole, the
      blood pressures in the RAo and LAo equalize through the foramen, and the pressure
      in the LAo therefore remains higher (under most circumstances) than that
      generated by the right ventricle preventing the LAo valve from opening. Blood
      flow in the LAo is biphasic, with a reversal of blood flow in systole due to the
      closure of the foramen of Panizza by the medial cusp of the RAo valve. Under
      these circumstances net LAo flow is low, and due solely to flow through the
      foramen. When peak systolic right ventricular pressure rises above that in the
      LAo, the valve will open, producing a (partial) pulmonary bypass (right-to-left
      shunt). This may occur during pulmonary vasoconstriction, or when the systemic
      (and hence the LAo) blood pressure decreases.

PMID- 7827253
TI  - Cardio-respiratory modeling in fishes and the consequences of the evolution of
      airbreathing.
AB  - The microcirculation of the respiratory organ of water and air breathing
      vertebrates is similar and can be described as sheet flow. The gross morphologies
      of the systems, however, are very different and reflect the properties of the
      medium. The fish heart has a single ventricle that forces blood first through the
      gills and then through the body. The pressure in the gills is higher than in the
      systemic circulation, the reverse of the situation seen in mammals. The gill
      epithelium is thicker than that in the lung and is involved in ionic and acid
      base functions carried out in the kidney of mammals. Gills stick together in air.
      Therefore, fish breathe air using some other structure, such as the gut or mouth,
      the swimbladder, or the skin. The gills are retained for carbon dioxide excretion
      and ion and acid-base regulation. This results in a separation of oxygen uptake
      and carbon dioxide excretion. The gills are often modified in air-breathing fish
      such that venous blood flows to well developed gills for carbon dioxide and acid
      excretion, whereas oxygenated blood flow bypasses the gills. This is the
      beginning of a separation of flows in the heart which is more highly developed in
      amphibians and reptiles and complete in mammals. The loss of gills requires
      transfer of ionic and acid base regulation processes to the skin in amphibia and
      to the kidney in reptiles and mammals, allowing a completely terrestrial
      existence. The organization of the venous system is influenced by the degree of
      support offered by the medium.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7827254
TI  - The evolution of efferent vagal control of the heart in vertebrates.
AB  - In vertebrates vagal preganglionic neurons are found in two principle locations
      in the brain-stem, the dorsal vagal motor nucleus and areas lateral to the dorsal
      vagal motor nucleus centered on the nucleus ambiguus. In elasmobranch fish 8% of
      vagal preganglionic neurons are located outside the dorsal vagal motor nucleus;
      these are all cardiac vagal motoneurones. This proportion increases from fish
      through amphibians to mammals in which over 30% of vagal preganglionic neurons
      are outside the dorsal vagal motor nucleus; in the cat 80% of cardiac vagal
      motoneurons are in the nucleus ambiguus. Vagal tone is the major determinant of
      heart rate and its relationships to environmental factors (e.g. temperature,
      hypoxia). Activity in subpopulations of cardiac vagal motoneurons varies with the
      respiratory rhythm in fish and mammals due to central interactions between
      respiratory and cardiac vagal motoneurons. This generates cardio-respiratory
      synchrony in dogfish and respiratory sinus arrhythmia in mammals. The appropriate
      central connections are established during development. In the neotenous axolotl
      all vagal preganglionic neurons are in the dorsal vagal motor nucleus; 15% are
      lateral to the dorsal vagal motor nucleus following metamorphosis, induced by
      injection of thyroid hormones; a change which may relate in part to the switch
      from gill to lung-breathing. Respiratory sinus arrhythmia first appears at around
      normal term gestation in the premature human neonate, at a time when they would
      normally be switching from reliance on the placenta to lung-breathing.

PMID- 7827255
TI  - Patterns of form and function in developing hearts: contributions from non
      mammalian vertebrates.
AB  - Although most research on developmental cardiovascular physiology has focused on
      the bird embryo as a model for emulating developmental processes in mammals,
      there are increasingly compelling reasons to expand research to a variety of
      lower vertebrate systems. These reasons include circumventing inherent
      limitations of the avian embryo and identifying general vertebrate developmental
      patterns in the cardiovascular system. In this paper, we first review data from
      hemodynamic studies on amphibians and birds (and what little exists from fish and
      reptiles), to provide a background against which lower vertebrate development can
      be examined. We then describe non-mammalian, non-avian paradigms for studying
      developmental patterns of vertebrate hearts. Developmental spects of
      cardiovascular performance, especially heart rate, blood pressure and cardiac
      output and how they change with ontogeny, are described for several amphibians
      and a few reptiles, identifying, where possible, processes in common with birds
      and mammals. Finally, we indicate productive areas for future research with lower
      vertebrate cardiovascular systems, such as establishing "critical windows" for
      cardiovascular physiology during development, and determining the extent of
      developmental plasticity at the level of organ system physiology.

PMID- 7827256
TI  - Comparison of the effects of carnitine palmitoyltransferase-1 and -2 inhibitors
      on rat heart hypertrophy.
AB  - Rats treated orally for 21 days with aminocarnitine, an inhibitor of carnitine
      palmitoyltransferase-2 (CPT-2), do not show hypertrophy of the heart. This
      contrasts with the effects of carnitine palmitoyltransferase-1 (CPT-1)
      inhibitors, that, according to the literature, cause hypertrophy. As CPT-1 and
      CPT-2 are both required for the oxidation of long-chain fatty acids in
      mitochondria, it can be concluded that inhibition of fatty acid oxidation per se
      is not responsible for cell growth, but rather the accumulation of a metabolite,
      probably long-chain acylcoenzyme A. CPT-1 and CPT-2 inhibitors cause different
      metabolic changes in the heart. Electron microscopy of hearts fixed 1 hour after
      Langendorff perfusion with the two types of inhibitors reveals some of these
      changes. Multilamellar vesicles were observed with aminocarnitine (CPT-2
      inhibitor) but not with etomoxir (CPT-1 inhibitor). When both inhibitors were
      present, electron-dense spots adjacent to mitochondria were observed, possibly
      containing long-chain acylaminocarnitine.

PMID- 7827257
TI  - Endocardial endothelium selectively modifies relaxation in rat papillary muscle.
AB  - The selective removal of endocardial endothelium of rat left ventricular
      papillary muscles by 1-second immersion in 0.5% Triton X-100 showed little
      influence on resting tension and only a small decrease in peak isometric tension
      (8.3 +/- 1.4 vs 9.6 +/- 2.4 mN/mm2 at Lmax, p > 0.05) with no reduction in
      maximal rate of tension development (+dT/dtmax; 136 +/- 21 vs 137 +/- 18
      mN/mm2/s, p > 0.05). In contrast, there was a marked increase in maximal rate of
      tension decline (-dT/dtmax) from 71 +/- 14 to 92 +/- 15 mN/mm2/s (p < 0.05), so
      that the ratio between +dT/dtmax and -dT/dtmax fell from 1.98 +/- 0.27 to 1.51 +/
      0.13 (p < 0.01). Removal of endocardial endothelium led to a significant
      shortening of isometric twitch contractions. Time to peak tension was abbreviated
      from 111 +/- 20 to 84 +/- 8 ms (p < 0.05) and the half relaxation time from 92 +/
      9 to 68 +/- 8 ms (p < 0.01). Time to +dT/dtmax was also shortened from 31 +/- 6
      to 44 +/- 9 ms (p < 0.05) and time to -dT/dtmax from 90 +/- 12 to 62 +/- 10 ms (p
      < 0.01). These effects were not influenced by alterations in stimulation
      frequency or muscle length. The early onset of relaxation and abbreviated
      duration of relaxation together with an increased rate of decline in tension led
      to a shorter total twitch which may explain the slightly lower peak tension once
      the endocardial endothelium was removed. Our findings confirm that endocardial
      endothelium modulates myocardial contraction, with a predominant influence on
      relaxation.

PMID- 7827258
TI  - Changes in nuclear size of cardiac myocytes during the development and
      progression of hypertrophy in rats.
AB  - It is generally believed that nuclear enlargement indicates polyploidy. The
      purpose of this study was to establish whether nuclear enlargement is also a
      marker for cellular hypertrophy. Using isolated myocytes, we examined the growth
      of cardiac myocyte nuclei during cellular hypertrophy in rats with aortocaval
      fistulas or left ventricular myocardial infarction. A Coulter Channelyzer was
      used to measure the volume of the myocytes. Isolated myocytes were stained with
      the DNA-specific fluorochrome 4'-6-di-amidino-2 phenylindole-HCl for measurements
      of nuclear length and width, and calculation of nuclear volume. One week, 1 month
      and 5 months after aortocaval fistula surgery, the nuclear volume of right
      ventricular myocytes increased by 24, 55 and 56% respectively. Increased length,
      rather than width, accounted for most of the nuclear growth. Nuclear hypertrophy
      was associated with a progressive increase in cell volume at each time point (34,
      88 and 118%). Adaptive growth of left ventricular myocytes followed the same
      trend, though the extent of cellular and nuclear hypertrophy was reduced. One
      month after producing a myocardial infarction, there was an increase in nuclear
      volume (18%) and nuclear length (11%) in right ventricular myocytes, but no
      changes in the surviving left ventricular myocytes. The cell volume increased in
      both right and left ventricles (72 and 18%, respectively). Thus, nuclear size
      increased as myocytes enlarged, though at a slower rate. Since nuclear DNA
      content does not increase in rats with aortocaval fistulas or myocardial
      infarction, the increase in nuclear volume was associated with cellular
      enlargement rather than increased polyploidy.

PMID- 7827259
TI  - A crystal structure with features of an antiparallel alpha-pleated sheet.
AB  - A single-crystal x-ray diffraction analysis of Boc-L-Ala-D-aIle-L-Ile-OMe has
      been carried out. The analysis has shown (a) that the tripeptide molecules have
      in part an alpha-extended conformation, the torsion angles of the L-Ala and D
      aIle residues being psi 1 = -75.1 degrees and psi 1 = -25.8 degrees and psi 2 =
      67.3 degrees and psi 2 = 44.1 degrees, respectively, and (b) that the molecules
      are organized in rippled planes where they occur in relative antiparallel
      orientation linked together side by side by H bonds. This molecular organization
      of the tripeptide corresponds closely to that of an antiparallel alpha-pleated
      sheet, and likely constitutes the first example of a structure of this kind for
      which a characterization at the atomic level has been achieved. A molecular
      dynamics study has shown that the molecular conformation of the tripeptide in the
      crystalline state is determined primarily by intermolecular interactions.

PMID- 7827260
TI  - Flow linear dichroism and Fourier transform IR spectra reveal geometry for X-form
      DNA.
AB  - Flow linear dichroism measurements extended into the vacuum uv region yield
      inclinations for the base normal from the helix axis of 21 degrees for dA and 40
      degrees for dT in the X-form of poly(dAdT).poly(dAdT). These inclination angles
      are similar to the B form of the synthetic polymer, but the axes around which the
      bases incline are different. Hydrogen-bonded base pairs are consistent with the
      geometry for the standard B, C, D, and Z forms of natural DNA, but will not fit
      into the A form. Fourier transform ir spectra indicate that the X form has sugar
      pucker and phosphate geometry similar to B-form DNA, and supports the
      dinucleotide repeat with two kinds of phosphates seen in earlier work, in analogy
      to Z-form DNA. Clearly, X-form DNA has a unique geometry.

PMID- 7827261
TI  - Nuclear Overhauser effect spectroscopy (NOESY) detection of the specific
      interaction between substituents in cellulose and amylose triacetates.
AB  - Nuclear Overhauser effect spectroscopy measurements on cellulose triacetate and
      on amylose triacetate with a mixing time of 500 ms, on the order of T1 of acetyl
      protons, were performed to detect the specific through-space interaction between
      acetyl groups arising from their helix structures in solution. For cellulose
      triacetate, cross peaks were detected in CDCl3 between acetyl proton signals at 3
      and 6 positions on an anhydroglucose unit. In DMSO-d6, on the other hand,
      correlation peaks were observed not only between the 3 and 6 positions but also
      the 2 and 6 positions. For amylose triacetate, cross peaks were detected in CDCl3
      between the acetyl proton signals at the 2 and 6 positions. The through-space
      interaction of acetyl groups in cellulose triacetate and in amylose triacetate in
      solution was then interpreted based on their three-dimensional structures in
      solid state determined by x-ray crystallography.

PMID- 7827262
TI  - Beta-alanine containing cyclic peptides with predetermined turned structure. V.
AB  - In the present paper we describe the synthesis, purification, single crystal x
      ray analysis, and solution structural characterization by nmr spectroscopy,
      combined with restrained molecular dynamic simulations, of the cyclic hexapeptide
      cyclo-(Pro-Phe-beta-Ala-Phe-Phe-beta-Ala). The peptide was synthesized by
      classical solution methods and the cyclization of the free hexapeptide was
      accomplished in good yields in diluted methylenechloride solution using N,N
      dicyclohexyl-carbodiimide. The compound crystallizes in the monoclinic space
      group P2(1) from methanol/ethyl acetate. The molecule adopts in the solid state a
      conformation characterized by cis beta-Ala6-Pro1 peptide bond. The alpha-amino
      acid residues are at the corner positions of turned structures. The Pro1-Phe2
      segment is incorporated in a pseudo type I beta-turn, while Phe4-Phe5 is in a
      typical type I beta-turn. Assignment of all 1H and 13C resonances was achieved by
      homo- and heteronuclear two-dimensional techniques in dimethylsulfoxide (DMSO)
      solutions. The conformational analysis was based on interproton distances derived
      from rotating frame nuclear Overhauser effect spectroscopy spectra and
      homonuclear coupling constants. Restrained molecular dynamic simulation in vacuo
      was also performed to built refined molecular models. The molecule is present in
      DMSO solution as two slowly interconverting conformers, characterized by a cis
      trans isomerism around the beta-Ala6-Pro1 peptide bond. This work confirms our
      expectations on the low propensity of beta-alanyl residues to be positioned at
      the corners of turned structure.

PMID- 7827263
TI  - Beta-alanine containing cyclic peptides with turned structure: the "pseudo type
      II beta-turn." VI.
AB  - In the present paper we describe the synthesis, purification, single crystal x
      ray analysis, and nmr solution characterization, combined with restrained
      molecular dynamic simulations, of the cyclic hexapeptide cyclo-(L-Pro-L-Phe-beta
      Ala)2. The peptide was synthesized by classical solution methods and the
      cyclization of the free hexapeptide was accomplished in good yields in diluted
      methylene chloride solution using N,N-dicyclohexyl-carbodiimide. The compound
      crystallizes in the monoclinic space group P2(1) from methanol-dichloromethane
      solution. The two identical halves of the molecule adopt in the solid state two
      different conformations. One beta-Ala-L-Pro peptide bond is trans, while the
      second is cis. The molecule is present in dimethylsulfoxide d6 solutions as a
      mixture of conformational families. One of these corresponds to a C2 symmetrical
      molecule with both beta-Ala-Pro cis peptide bonds, while the second major
      conformation is very similar to that observed in the solid state. All Pro-Phe
      segments, both in the solid state and the symmetrical and unsymmetrical solution
      conformations, display phi, psi angles close to that of position i + 1 and i + 2
      of type II beta-turns. In addition, the segments preceded by a trans beta-Ala-Pro
      peptide bond are characterized by a typical i<--i + 3 hydrogen bond, which is
      absent in the conformer containing a cis beta-Ala-Pro peptide bond. The latter
      conformation corresponds to a new structural domain we define as the "pseudo type
      II beta-turn."

PMID- 7827264
TI  - A conformational study of agarose by vacuum UV CD.
AB  - Agarose films were prepared using a variety of casting conditions, heat
      treatments, and solvation treatments. Films represented the high temperature sol,
      the room temperature gel, and a high temperature state with cross-links intact.
      The vacuum uv CD of the film samples varies considerably, but the similarities
      between the film CD and the previously reported solution CD show that dehydration
      per se does not affect the CD. Combining the CD results for the dried sol with
      the x-ray results of Foord and Atkins leads to a description of the high
      temperature sol in terms of locally extended chain conformations. The CD of the
      gel and its peculiarly high uv absorption are satisfactorily, albeit not
      uniquely, interpreted in terms of the double-helix model of the gel, in agreement
      with previous conformational studies based on chiroptical properties.

PMID- 7827265
TI  - Conformation of retro-bombolitin I in aqueous solution containing surfactant
      micelles.
AB  - Bombolitins are five naturally occurring heptadecapeptides acting at the membrane
      level and able to increase the activity of phospholipase A2. As for other
      peptides with similar function, the biological activity of bombolitins seems to
      be mainly due to their ability to form amphipathic helical structures. We
      synthesized and tested the retro sequence of bombolitin I (retro-bombolitin I).
      This peptide showed an activity similar to that of the natural sequence and was
      able to adopt a helical structure in the presence of an amphipathic environment
      consisting of SDS micelles. The secondary structure of this peptide was fully
      characterized by CD and nmr spectroscopy.

PMID- 7827266
TI  - Redox-active bis-cysteinyl peptides. I. Synthesis of cyclic cystinyl peptides by
      conventional methods in solution and on solid supports.
AB  - Cyclic mono-cystinyl active-site fragments of thioredoxin and thioredoxin
      reductase were synthesized as N-acetyl and C-amide octapeptides by conventional
      methods of peptide synthesis in solution and on solid supports. Using a side
      chain protection based on acid-labile tert-butanol-derived groups and on the S
      tert-butylthio unsymmetric disulfide for the thiol functions, in combination with
      N alpha-Z- or N alpha-Nps derivatives in the chain elongation steps, the
      synthesis in solution was carried out in straightforward manner yielding the
      fully protected octapeptides as well characterized compounds. Upon deprotection
      with trifluoroacetic acid and reduction of the unsymmetrical disulfides with tri
      butylphosphine, the resulting bis-cysteinyl-octapeptides were oxidized in
      dimethylformamide with azodicarboxylic acid di-tert-butyl ester to produce the
      desired cyclic compounds in good overall yields. For the synthesis on solid
      supports a similar acid-labile side-chain protection was applied in combination
      with the N alpha 9-flourenylmethyoxycarbonyl derivatives in the chain elongation
      steps. Thereby acylations were performed with the related amino acid N
      carboxyanhydrides (UNCAs) or by the O-(1H-benzotriazol-1-yl)-N,N,N',N'
      tetramethyluronium-tetraf luoroborate/1- hydroxybenzotriazole (TBTU/HOBt)
      procedure. The solid phase synthesis of the two octapeptides led to unexpected
      difficulties in terms of recovery of peptidic material from the resins in the
      final acidolytic cleavage step as well as of racemization at the level of the
      cysteine residues by the TBTU/HOBt coupling method. Racemization was efficiently
      suppressed by employing the related pentafluorophenyl ester and this method led
      to crude octapeptide products of a degree of purity comparable to those obtained
      by the synthesis in solution. However, the recovery of the peptides from the
      resin, i.e., irreversible reattachment of cleaved peptidic material via
      alkylation of various side-chain functions, could not be avoided even using the
      most efficient scavengers or their cocktails.

PMID- 7827267
TI  - Redox-active bis-cysteinyl peptides. II. Comparative study on the sequence
      dependent tendency for disulfide loop formation.
AB  - Bis(cysteinyl)octapeptides related to the active sites of the oxidoreductases
      protein disulfide isomerase (PDI), thioredoxin reductase (trr), glutaredoxin
      (grx), and thioredoxin (trx) were analyzed for their propensity to form the
      intramolecular 14-membered disulfide ring in oxidation experiments. The rank
      order of percentage of cyclic monomer formed in aqueous buffer (pH 7.0) at 10(-3)
      M concentration was found to be very similar, but opposite to that of the Kox
      and, correspondingly, of the redox potentials of the native enzymes. Attempts to
      induce intrinsic conformational preferences of the peptides by addition of
      trifluoroethanol led to enhancements of beta-turn structures as reflected by the
      CD and Fourier transform ir spectra. The induced secondary structure, instead of
      aligning the tendencies of the excised fragments for loop formation with those of
      the intact proteins, was found to suppress the differences by significantly
      increasing the preference for cyclic monomers (approximately 90%). Similarly,
      operating under denaturing conditions, i.e., in 6 M guanidinium hydrochloride,
      only for the trx peptide was the statistical product distribution obtained. For
      the remaining peptides, again a strong increase of cyclic monomer contents was
      observed that could not be correlated with dissolution of beta-sheet type
      aggregates. The CD spectra are more consistent with the presence of ordered
      structure to some extent, possibly resulting from an hydrophobic collapse of the
      sparingly soluble peptides. The results of the oxidation experiments further
      support previous findings from thiol disulfide interchange equilibria, which
      clearly revealed a decisive role of the characteristic thioredoxin structural
      motif in dictating the redox properties of the enzymes. Point mutations in the
      active sites of the oxidoreductases allowed us to affect their redox potentials
      strongly, but apparently only in the constraint form of the three-dimensional
      structure as similar exchanges in the excised fragments did not produce the
      expected effect. This observation contrasts with numerous reports that the
      conformation of short disulfide loops is mainly dictated by the amino acid
      sequence.

PMID- 7827268
TI  - Nutrition during pregnancy.
AB  - Nutrition during pregnancy has become an integral component of prenatal care.
      This review will focus on new topics and recent research on established areas,
      including the influence of caffeine on infertility, intrauterine growth,
      prematurity, and fetal behaviours; anthropometric factors influencing birthweight
      and maternal weight postpartum, and during lactation; the cost-benefit of
      prenatal outcomes; and the influence of smoking and individual nutrients,
      including n-3 fatty acids, vitamin K, and folic acid, on reproductive outcome.

PMID- 7827269
TI  - Anesthesia in obstetrics.
AB  - Some of the topics which have generated particular interest in obstetric
      anesthesia recently include the effects of epidural anesthesia on the progress of
      labor, the efficacy of volume preloading prior to spinal anesthesia for cesarean
      section, and the use of intraspinal opioids and of alpha-2 adrenergic agonists
      for labor analgesia.

PMID- 7827270
TI  - Forceps and vacuum extraction.
AB  - The proper use of forceps or vacuum extractor, or both, remains a safe and
      effective modality in achieving the universal goal of a healthy mother and baby.
      Their use requires continued experience, sharing of information, and possibly
      attention to subtleties of design. This review looks at the current situation
      with special emphasis on side effects and selection issues as found in the recent
      literature.

PMID- 7827271
TI  - Vaginal birth after cesarean section: an update on physician trends and patient
      perceptions.
AB  - The increased number of women having a vaginal birth after a cesarean section can
      be attributed to changing physician trends. Women eligible for vaginal birth
      after cesarean section include those with previous low vertical incisions,
      multiple previous incisions and even unknown scars, regardless of the method of
      closure or previous indication. Limited data suggest that in carefully selected
      women a current twin gestation, breech presentation, or the presence of fetal
      macrosomia are not contraindications for a trial of labor, in the presence of a
      uterine scar. Changing trends in the management of labor may also contribute to
      an increase in successful trial of labor with the use of oxytocin for the
      induction or augmentation of labor, the administration of epidural anesthesia for
      pain relief, and the instillation of prostaglandin E2 gel for cervical ripening.
      External cephalic version and amnioinfusion may also be reasonable alternatives
      in appropriately selected cases. Despite the documented safety and success of
      vaginal birth after cesarean section, and the lack of increased morbidity of
      failed trial of labor, 50% of women who are eligible for vaginal birth after
      cesarean section will decline an attempt, even after extensive counseling and
      encouragement. Patient resistance, largely attributed to the fear and
      inconvenience of labor, is still a major deterrent to a further rise in vaginal
      birth after cesarean section rates.

PMID- 7827272
TI  - Routine ultrasound screening.
AB  - In the USA, the cost-effective use of health-care dollars is currently of great
      importance. The routine use of technology such as ultrasound will undergo great
      scrutiny. Both the American College of Obstetricians and Gynecologists and the US
      National Institutes of Health have recommended that ultrasound be used only for
      indicated reasons because of concerns about safety and efficacy.

PMID- 7827273
TI  - Fetal monitoring: medical and legal implications for the practitioner.
AB  - Seventy per cent of all claims concerning intrapartum care in relation to fetal
      brain damage are based on abnormalities of the cardiotocograms and electronic
      fetal monitoring. Claims arise because of failure to take action in the presence
      of an abnormal cardiotocogram, or because of delayed response to an abnormal
      tracing. Difficulties in court arise from variations in the interpretation of the
      significance of recordings. The importance of taking appropriate action in the
      presence of an abnormal cardiotocogram, and in keeping accurate time-sensitive
      records is emphasized.

PMID- 7827274
TI  - A clinical and ethical evaluation of routine obstetric ultrasound.

PMID- 7827275
TI  - Cordocentesis: direct access to the fetal circulation for evaluating fetal
      wellbeing and thyroid function.
AB  - Cordocentesis has pioneered perinatal medicine in the last 10 years with the
      ability to obtain genetic information, to diagnose and to treat erythrocyte and
      platelet alloimmunization, to discover the presence of perinatal infections, and
      to determine the acid-base status of the fetus. Fetal blood sampling has also
      allowed the perinatologist a greater understanding of fetal physiology, such as
      thyroid-pituitary function. This review will concentrate on the role of
      cordocentesis in determining fetal physiology with acid-base status, compare
      noninvasive testing in its prediction of the hypoxic-acidemic state, and also how
      cordocentesis has enabled obstretricians to have a better understanding of fetal
      thyroid development and function.

PMID- 7827276
TI  - Genetics and DNA technology.
AB  - Recent advances in molecular biology have both expanded and enhanced our ability
      to prenatally diagnose genetic diseases. The new techniques involved will be
      discussed, as will their applicability to different diagnostic methods and to
      gene replacement therapy (a novel approach to the correction of genetic defects).

PMID- 7827277
TI  - Biochemical screening.
AB  - The goal of screening both low and high risk obstetrics populations for
      chromosomally abnormal fetuses continues to be developed in many centers
      worldwide. Advances in the past year have been multifocal in their approach-
      neural tube detection, the development of new markers for aneuploidy, and
      attempts to move screening into the first trimester.

PMID- 7827278
TI  - Prenatal diagnosis of major congenital malformations.
AB  - Congenital malformations affect approximately 2-3% of all live births every year.
      Several of these are associated with in-utero fetal demise or may account for
      significant neonatal morbidity and mortality. Therefore, it is important that,
      when possible, congenital anomalies are diagnosed during the antenatal period to
      allow adequate counseling of the mother and to permit preparation of the neonatal
      care team to optimize the outcome. The role of ultrasound in perinatal medicine
      has expanded over the past two decades. Previously, B-mode sonography allowed for
      the detection of multiple gestations, fetal biometry, and basic antenatal
      diagnosis of congenital anomalies. The technology has since rapidly advanced to
      the point that even subtle abnormalities are amenable to antenatal diagnosis.
      Perinatal medicine has advanced concurrently with these technological
      breakthroughs, and as a result, the possibilities for in-utero therapy and
      potential surgery have markedly improved. This article reviews the types and
      incidences of the various anomalies that are detectable by antenatal
      ultrasonography using a systematic approach; highlights the prenatal diagnostic
      and therapeutic strategies; discusses the obstetrics and medical management of
      pregnancies complicated by these conditions, and presents the neonatal prognosis
      and the recurrence risks for subsequent pregnancies.

PMID- 7827279
TI  - Fetal therapy.
AB  - Twin to twin transfusion syndrome and twin reversed arterial perfusion sequence
      affect up to 15% of monozygotic twin pregnancies. They can lead to miscarriage or
      very premature delivery, and fetal death. Intrauterine treatment is leading to an
      increased rate of survival of at least one twin in affected pregnancies.

PMID- 7827280
TI  - Doppler ultrasound in all three trimesters of pregnancy.
AB  - Doppler ultrasound velocimetry of uteroplacental, umbilical, and fetal vessels
      provides the clinician with important information on the hemodynamics of the
      vascular area under study. Transvaginal color Doppler is a new technique that
      allows precise investigation of fetomaternal circulation in early pregnancy.
      Doppler can be used to follow physiologic hemodynamic changes in uteroplacental
      and fetal vessels in this period of gestation, and to measure circulatory
      disturbances in some pathologic conditions. In late pregnancy, Doppler is a
      useful diagnostic tool for monitoring fetuses with intrauterine growth
      retardation. Doppler is a better predictor of perinatal morbidity than other
      methods of fetal surveillance. Recent investigations have shown that fetal vein
      flow affects fetal wellbeing. Randomized control trials have given different
      answers about the cost-effectiveness of Doppler in obstetrics.

PMID- 7827281
TI  - Bronchopulmonary sequestration: prenatal diagnosis with clinicopathologic
      correlation.
AB  - A patient was referred at 21 weeks' gestation for evaluation of an echogenic mass
      in the fetal right chest. Color-doppler sonography facilitated the diagnosis of a
      bronchopulmonary sequestration. Clinicopathologic correlation was possible after
      termination at 2.3 weeks' gestation. Pathologic examination confirmed the
      prenatal diagnosis and demonstrated the systemic vascular supply seen on color
      doppler sonography. Color doppler is a useful adjunct in the sonographic
      evaluation of the fetus with an echogenic chest mass.

PMID- 7827282
TI  - Molecular cloning and expression of canine interleukin 8 cDNA.
AB  - Molecular cloning of canine interleukin-8 (IL-8) was performed to establish a
      basis for its investigation in the canine immune system. From a cDNA pool
      constructed from LPS-stimulated popliteal lymph node cells, canine IL-8 cDNA
      covering the whole coding region was amplified by polymerase chain reaction. The
      nucleotide sequence of a canine IL-8 clone, designated pcIL-8#38, was highly
      similar to those of human, rabbit and porcine IL-8, and comprised 353 bp with an
      open reading frame that encoded 101 amino acids. Analysis of the deduced amino
      acid sequence of insert DNA in pcIL-8#38 showed 76.5, 80.2, and 87.0%
      similarities with human, rabbit and porcine IL-8 proteins, respectively. Insert
      DNA of pcIL-8#38 was transferred to a mammalian expression vector, pcDL-SR alpha
      296, and transfected into Cos7 cells. The supernatant of the transfectant had
      neutrophil chemotactic activity when it was examined by the neutrophil migration
      assay, suggesting that our cloned cDNA was biologically active. The cloned canine
      IL-8 cDNA will be useful for canine inflammatory disease and comparative
      immunology research.

PMID- 7827283
TI  - Suppression of the allogeneic response by human IL-10: a critical role for
      suppression of a synergy between IL-2 and TNF-alpha.
AB  - The effect of IL-10 on T-cell activation by alloantigens in primary mixed
      lymphocyte reaction (MLR) was examined. IL-10 strongly suppressed proliferation
      and cytokine synthesis observed in this reaction. To determine the cytokine
      synthesis inhibition that was critical for the IL-10 induced suppression of
      proliferation in MLR, the effect of exogenous cytokines (IL-1 alpha, IL-1 beta,
      IL-2, IL-4, IL-6, IFN-gamma, or TNF-alpha) on this suppression was examined. None
      of these cytokines, when used at high concentration, was able to completely
      restore proliferation in the MLR to the levels observed in the absence of IL-10.
      However, IL-2 and TNF-alpha, when added alone at high concentration, could
      partially overcome the IL-10 induced suppression of proliferation in MLR.
      Moreover, when a combination of IL-2 and TNF-alpha was added at suboptimal doses
      to IL-10-suppressed MLR, complete restoration of the proliferative response was
      obtained. The ability of IL-10 to suppress proliferation in MLR was dependent on
      the type of cells used as stimulators. Thus, IL-10 suppressed proliferation in
      MLR when allogeneic normal peripheral blood mononuclear cells (PBMC), highly
      purified monocytes or B cells, were used, but not when B-cell lines were used as
      stimulators. Investigation of the effect of IL-10 on cytokine synthesis revealed
      that when B-cell lines were used as stimulators of MLR, IL-10 suppressed IFN
      gamma and IL-2 synthesis but was unable to suppress TNF-alpha production. In
      contrast, CSA, which inhibited proliferation in MLR induced by B-cell lines, also
      inhibited TNF-alpha. IL-2 and IFN-gamma synthesis. Together these data suggest
      that the suppression of MLR by IL-10 requires the effective inhibition of both IL
      2 and TNF-alpha production to suppress a synergy between these two cytokines.

PMID- 7827284
TI  - Cyclophosphamide uncovers two separate macrophage subpopulations with opposite
      immunogenic potential and different patterns of monokine production.
AB  - As shown previously, thioglycollate-induced peritoneal macrophages consist of two
      subpopulations which differ morphologically and functionally. When tagged with
      trinitrophenyl hapten (TNP), one macrophage subpopulation induced in vivo
      effector cells (Th1) of contact sensitivity (CS) reaction, while the other
      induced suppressor T cells (Ts) which inhibit CS and are highly sensitive to the
      in vivo action of cyclophosphamide (CY). Our present experiments show that CY
      resistant (Th inducers) and CY-sensitive macrophages (Ts inducers) differ also in
      the spectrum of biologically relevant molecules which they secrete when
      stimulated by LPS. Thus macrophages which preferentially induce Th1 cells have a
      cytokine pattern IL-1LOW, IL-6HIGH, TNF-alpha LOW, while macrophages which
      recruit Ts cells are IL-1HIGH, IL-6LOW, TNF-alpha HIGH. TH1 inducers produced
      also somewhat better PGE2 then Ts inducers. Production of reactive nitrogen
      intermediates (NO/NO2-) was similar in both groups of macrophages. The reasons
      for the differential effect of CY on these two populations is not clear at
      present, although it is known that CY metabolites can bind to sulfhydryl groups
      on antigen presenting cells (APC) and thereby up- or downregulate the antigen
      presenting capacities of separate subpopulations of APC.

PMID- 7827285
TI  - Cytokines induce catabolic effects in cultured adipocytes by multiple mechanisms.
AB  - Previous studies have demonstrated that some cytokines induce a coordinate
      catabolic response in adipose cells which leads to decreased fat storage. The
      mechanisms by which cytokines cause these effects are unknown. The primary
      purpose of the present study was to determine the effects of TNF, IL-1, IFN-alpha
      and IFN-alpha on the mRNA levels of the key enzymes involved in fat metabolism in
      3T3-F442A adipocytes. TNF, IL-1, IFN-alpha and IFN-gamma decreased lipoprotein
      lipase activity and increased lipolysis in adipocytes. TNF, IFN-alpha and IFN
      gamma decreased fatty acid synthesis while IL-1 increased fatty acid synthesis.
      However, the cytokine effects on mRNA levels were not always consistent with the
      observed changes in activity and were unique for each cytokine. Specifically,
      while all cytokines decreased LPL activity, only TNF and IFN-gamma decreased LPL
      mRNA levels. In addition, while TNF, IFN-alpha and IFN-gamma decreased fatty acid
      synthesis, only TNF significantly decreased the mRNA levels of both acetyl CoA
      carboxylase and fatty acid synthase, the key enzymes in fatty acid synthesis. IFN
      alpha and IFN-gamma decreased fatty acid synthase mRNA levels without
      significantly altering acetyl CoA carboxylase mRNA. IL-1 caused a slight increase
      in fatty acid synthesis and increased acetyl CoA carboxylase mRNA levels.
      Finally, while all cytokines increased lipolysis, hormone sensitive lipase mRNA
      levels were decreased by TNF, IFN-alpha and IFN-gamma treatment. These results
      indicate that the regulation of adipocyte lipid metabolism by cytokines is
      complex and that coordinate changes in mRNA levels cannot account for the
      observed metabolic changes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7827286
TI  - Presence of leukaemia inhibitory factor and interleukin 6 in porcine uterine
      secretions prior to conceptus attachment.
AB  - Leukaemia inhibitory factor (LIF) plays an important role in embryo development
      and implantation. We detected peak LIF activity in porcine uterine luminal fluids
      (ULF) at day 12 of gestation and during day 7 and 13 of the oestrous cycle. A
      radio-receptor competition assay showed the presence of a molecule in ULF
      specifically binding to human LIF receptor (LIF-R). LIF activity was partially
      neutralized by anti-human LIF antibody. Interleukin-6 (IL-6) activity was
      detected in ULF throughout the oestrous cycle and pre-implantation period. An
      anti-murine alpha chain (gp80) of IL-6 receptor (IL-6R) specifically neutralized
      this activity. LIF and IL-6 mRNA were only detected in day 11 endometrium. The
      presence of LIF or IL-6 in the uterine cavity has not been previously reported.
      Our results extend LIF production by endometrium during the oestrous cycle and
      pre-implantation period to another mammalian species other than mouse.

PMID- 7827287
TI  - Cyclooxygenase inhibitors enhance tumour necrosis factor production and mortality
      in murine endotoxic shock.
AB  - Intraperitoneal administration of E. coli lipopolysaccharide (5-15 mg/kg)
      produced a dose-related increase in mortality which was maximal 72 h after
      induction of shock. Using a suboptimal dose of LPS (10 mg/kg i.p.), pretreatment
      with indomethacin (0.1-10 mg/kg p.o) or ibuprofen (1-100 mg/kg p.o) 30 min prior
      to induction of shock led to a significant enhancement of mortality. This
      enhancement was associated with a 2-3 fold increase in the peak circulating
      levels of tumour necrosis factor (TNF-alpha) in the serum of animals treated with
      indomethacin or ibuprofen compared to vehicle-treated control animals. These
      results indicate that TNF-alpha production is modulated by endogenous
      prostaglandins in vivo and that enhanced production of TNF-alpha by
      cyclooxygenase inhibitors may lead to exacerbation of some inflammatory
      processes.

PMID- 7827288
TI  - Transcriptional and translational regulation of IL-1 alpha and IL-1 beta account
      for the control of IL-1 in experimental yersiniosis.
AB  - Interleukin 1 (IL-1) gene expression was investigated in mice following oral
      infection with Yersinia enterocolitica 08. In Peyer's patches (PP), the primary
      site of bacterial invasion, induction of IL-1 alpha mRNA was delayed when
      compared to IL-1 beta mRNA. As shown by in situ hybridization. IL-1 alpha and IL
      1 beta mRNA were found to be expressed within different cell types. These results
      indicate that expression of the two forms of IL-1 is regulated in a cell-specific
      manner at the transcriptional level. Moreover, IL-1 (alpha and beta) mRNA was
      increased in other organs such as spleen and lung. In spleens, IL-1 beta mRNA was
      found within the red pulp, and IL-1 alpha mRNA was located to the marginal zone
      confirming that differential expression of IL-1 alpha and IL-1 beta mRNA does not
      represent a tissue-specific event. However, as revealed by immunohistochemistry
      and measuring IL-1 activity in tissue homogenates, synthesis of IL-1 proteins was
      not detectable in spleens, unless mice were challenged with LPS. Because IL-1
      synthesis was inducible in spleen cells following actinomycin D treatment, the
      results indicate that at distant sites of infection IL-1 (alpha and beta) mRNA is
      expressed but not translated into protein. It is concluded that cell-specific
      transcription of IL-1 alpha and IL-1 beta as well as dissociation between IL-1
      mRNA and protein synthesis are two mechanisms effective in regulating the
      production of IL-1 during infection.

PMID- 7827289
TI  - Endotoxin and tumour necrosis factor do not cause mortality from caecal ligation
      and puncture.
AB  - Macrophage tumour necrosis factor-alpha (TNF-alpha) production is thought to
      represent an important pathogenic mechanism by which Gram-negative sepsis is
      mediated. We compared the effects of caecal ligation and puncture (CLP) on
      endotoxin-sensitive (C3H/HeSnJ) and endotoxin-resistant (C3H/HeJ) mice. Mortality
      after CLP for C3H/HeSnJ mice compared with C3H/HeJ mice was not significantly
      different (32% and 55%, respectively). When survivors were injected with
      lipopolysaccharide intraperitoneally on the 7th day after CLP, the mortality rate
      was 82% for C3H/HeSnJ mice versus 0% for C3H/HeJ mice (P < 0.0001). Serum
      endotoxin levels at 24 h after CLP were only slightly elevated. Serum TNF levels
      and peritoneal macrophage TNF production were undetectable in C3H/HeJ mice and
      were only slightly elevated in C3H/HeSnJ mice by 24 h after CLP. Peritoneal
      macrophage mRNA levels for TNF-alpha, IL-1 beta, and I-A alpha displayed a
      similar pattern in the two strains of mice, with a 2- to 3-fold increase in TNF
      alpha and IL-1 beta mRNA levels by 24 h and a sharp decrease in I-A alpha mRNA by
      24 h. The cause of mortality in mice that undergo CLP cannot be attributed to
      overwhelming endotoxemia and/or TNF production.

PMID- 7827290
TI  - Analyses of proliferating cell nuclear antigen-positive cells in hepatocellular
      carcinoma: comparisons with clinical findings.
AB  - Proliferating tumour cells in 92 patients with hepatocellular carcinoma (HCC)
      were identified by an immunohistochemical method using a monoclonal antibody
      against proliferating cell nuclear antigen (PCNA). The rate of PCNA-positive
      cells in HCC tissues was positively correlated with histological grade and the
      tumour size and T factor of the tumour. In order to analyse the relationship
      between prognostic factors and cumulative survival rate after obtaining tumour
      specimens, 49 patients whose clinical courses could be followed after needle
      biopsy were selected for evaluation. These patients were treated by medical
      therapy alone. Analyses of prognostic factors by Cox's proportional hazard model
      revealed that the patient's prognosis was significantly correlated with PCNA
      positive rates as well as the tumour size and mode of therapy. Moreover, the
      cumulative survival rates were significantly (P < 0.001) higher in patients with
      rates of PCNA-positive cells < 15% than in those with > or = 15%, even when
      tumour sizes were under 50 mm or tumours demonstrated the same degree of
      histological differentiation. These findings indicate that the PCNA-positive rate
      in biopsied tissues provides useful prognostic information in patients with HCC
      treated only by medical therapy.

PMID- 7827291
TI  - Spontaneous bacterial peritonitis and culture negative neutrocytic ascites in
      patients with non-alcoholic liver cirrhosis.
AB  - Medical records of 18 patients with spontaneous bacterial peritonitis (SBP) and
      19 patients with culture negative neutrocytic ascites (CNNA) were reviewed. The
      diagnosis of SBP was based on a positive ascitic fluid culture, a
      polymorphonuclear cell count (PMN) greater than 250 cells/mm3 and the absence of
      an intra-abdominal source of infection. The diagnosis of CNNA was based on a PMN
      count greater than 250 cells/mm3, a negative ascitic fluid culture, the absence
      of an intra-abdominal source of infection and no antibiotic treatment in the
      preceding 30 days. All patients in both groups had liver cirrhosis, which was
      mainly (62.2%) due to HBV infection. A single strain, mostly 'a Gram-negative'
      bacillus, was recovered from the ascitic fluid culture in the vast majority of
      patients (83%) with SBP. There were no significant differences between the
      clinical data of both groups. However, the CNNA group had a significantly better
      Pugh score (P value = 0.01) with a mean score of 9.42 +/- 2.24, compared to the
      SBP group (10.94 +/- 2.88). The only significant difference in the laboratory
      data was that the total bilirubin was higher in the SBP group (P < 0.01).
      Hospital mortality was significantly higher in the SBP patients compared to those
      with CNNA, 50 and 16%, respectively (P < 0.03). Recurrent ascitic fluid infection
      occurred in one of five patients who initially presented. In contrast no
      recurrence was documented in 12 patients with CNNA. Spontaneous bacterial
      peritonitis is a serious complication of liver cirrhosis with significantly
      higher mortality than CNNA. A single organism, usually enteric, is the most
      common causative agent.

PMID- 7827292
TI  - Prolonged bleeding time in cirrhotic patients: relationship to peripheral
      vasodilation and severity of cirrhosis.
AB  - A prolonged bleeding time (> 540 s), measured with a Simplate single template
      device, was found in 0% of 50 patients with chronic hepatitis and 38% of 154
      cirrhotic patients. Cirrhotic patients with a prolonged bleeding time (n = 59)
      had lower platelet counts (P < 0.001) and a longer prothrombin time (P < 0.001)
      and activated partial thromboplastin time (P < 0.001) compared with cirrhotic
      patients with a normal bleeding time (n = 95). A weak but significant negative
      correlation existed between the bleeding time and platelet count in cirrhotic
      patients (n = 154, r = -0.3668, P < 0.001). Patients with decompensated cirrhosis
      had a longer bleeding time in comparison to patients with compensated cirrhosis
      (621 +/- 39 vs 478 +/- 27 s, respectively, P < 0.01). The prolonged bleeding time
      was also discovered in 25% of 83 cirrhotic patients with a platelet count > 80 x
      10(9)/L and a prothrombin time < 17 s (usually taken as safe limits for invasive
      procedures). Twenty-seven of the 83 cirrhotic patients received a haemodynamic
      study by Swan-Ganz catheterization. A lower systemic vascular resistance was
      found in cirrhotic patients with an abnormal bleeding time than in cirrhotic
      patients with a normal bleeding time (844 +/- 57 vs 1171 +/- 60 dyne.s.cm-5,
      respectively, P < 0.001), whereas both groups had similar hepatic venous pressure
      gradient (16.2 +/- 1.2 vs 18.1 +/- 1.4 mmHg, respectively, P > 0.05).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7827293
TI  - Clinical characteristics and proliferating activity of intrahepatic
      cholangiocarcinoma.
AB  - To assist in the development of new approach to the palliation and treatment of
      intrahepatic cholangiocarcinomas, we classified tumours into mass-forming (MF),
      peri-ductal extension (PD), and spicula-forming (SF) types in 14 subjects who
      underwent surgical treatment. Lymph node metastasis and microscopic lymphatic
      invasion were pronounced in the PD and SF types. Furthermore, in SF type tumours
      the incidence of microscopic vascular and perineural invasion was high. The
      proliferating cell nuclear antigen labelling index, a reflection of the
      proliferation rate of tumour cells, was significantly higher in PD and SF types
      than in the MF type. The prognosis associated with the MF type tended to be
      better than that of the other two types. For the MF type, liver resection with
      tumour free margins must be performed, whereas for the PD and SF types,
      aggressive treatment, that is a combination of extensive liver resection, lymph
      node dissection, and effective adjuvant anti-cancer therapy should be provided to
      aim at life-long cure.

PMID- 7827294
TI  - The effect of simvastatin and bezafibrate on bile composition and gall-bladder
      emptying in female non-insulin-dependent diabetics.
AB  - Female non-insulin-dependent diabetics have a high prevalence of gallstones.
      Treatment of hyperlipidaemia in these patients may modify the risk. Seventeen
      female non-insulin-dependent diabetics (age 35-65) were treated with simvastatin
      (n = 10) or bezafibrate (n = 7) and had the cholesterol saturation index (CSI) of
      bile and gall-bladder emptying measured before and after 3 months therapy. In
      both groups, there was a significant reduction in serum cholesterol following
      treatment. The mean pretreatment cholesterol saturation indices of bile did not
      differ between the two groups but, after 3 months therapy, there was a highly
      significant difference in CSI between the bezafibrate group (2.0 +/- 0.33) and
      the simvastatin group (1.1 +/- 0.14) P < 0.002. Whereas the increase in the CSI
      (42%) observed with bezafibrate therapy was significant, the decrease in the
      simvastatin group (14%) was only significant in those whose pretreatment
      cholesterol saturation indices were elevated. Despite the differences in CSI
      observed between the two treatment groups, no changes in gall-bladder emptying
      were detected.

PMID- 7827295
TI  - Geographic variations in structure and composition of gallstones and their
      correlation with brittleness.
AB  - Cholesterol gallstones obtained from different geographic regions have been
      reported to show significant differences in their minor chemical constituents. We
      undertook the present study with two objectives: (i) to investigate the possible
      physiochemical and radiological differences between cholesterol gallstones
      obtained from Indian and German patients; and (ii) to compare the brittleness of
      the two stone groups. Forty Indian and 36 German gallstones (matched in size and
      shape) were subjected to assessment of physical characteristics, in vitro
      computed tomography (CT) and chemical analysis. German stones more often had a
      stone density distribution index of > or = 50 Hounsfield units (HU) (26 vs 14; P
      < 0.01), peripheral calcification (18 vs 9; P < 0.02), maximum CT density > or =
      90 HU (17 vs 9; P < 0.05) and significant calcium carbonate (9 vs 5; P < 0.05),
      compared to Indian stones. The in vitro lithotripsy performed with the Siemens
      Lithostar Plus machine at a constant energy level showed the German stones to be
      more brittle (easy to fragment), more often requiring < 1000 shocks for
      fragmentation (25/36; 69%) compared to Indian stones (18/40; 45%, P < 0.05).
      Gallstones from different geographic regions may show significant variations in
      their physicochemical characteristics that may explain the differences in their
      brittleness to lithotripsy.

PMID- 7827296
TI  - Transjugular liver biopsy: comparison with percutaneous liver biopsy.
AB  - A transjugular liver biopsy was performed on 60 patients. Specimens were
      successfully obtained from 57 (95%) patients. Specimens obtained from cirrhotic
      patients were frequently small-sized/fragmented. The wedge hepatic venous
      pressure and hepatic venous pressure gradient were higher in patients with small
      sized/fragmented specimens than those with non-fragmented specimens (16.3 +/- 6.4
      vs 12.3 +/- 4.9 and 10.9 +/- 6.2 vs 7.3 +/- 3.4 mmHg, P < 0.05, respectively).
      During the same period of time, percutaneous liver biopsies were consecutively
      performed on 277 patients. The liver specimens by transjugular method were
      generally smaller (0.63 +/- 0.58 vs 1.50 +/- 0.86 cm, P < 0.001) and more
      fragmented (63% vs 16%, P < 0.01) than those obtained by percutaneous method.
      Biopsy specimens obtained for diagnosis by the former method were inadequate from
      6 (10%) patients and by the latter route were inadequate from 7 (2%) patients.
      Subcapsular haematoma in one patient was associated with the transjugular liver
      biopsy. Minor complications occurred in three patients: neck haematoma in two and
      paroxysmal supraventricular tachycardia during the procedure in one. In
      comparison, percutaneous liver biopsy was followed by minor complications in 20
      patients and major complications in four patients. It is concluded that
      transjugular liver biopsy is a safe, valuable and alternative procedure to obtain
      liver specimens, especially in patients who were contraindicated for percutaneous
      liver biopsy.

PMID- 7827297
TI  - Interleukin-6 functions as an autocrine growth factor in a cholangiocarcinoma
      cell line.
AB  - The tumour cells of a human cholangiocarcinoma cell line, HuCC-T1, were found to
      express mRNA of interleukin-6 (IL-6) and to secrete a large amount of
      biologically active IL-6 in the culture medium at the concentration of 22.6
      ng/mL. Interleukin-6 was demonstrated in the cytoplasm of the cells by
      immunohistochemical staining. Furthermore, these cells showed the presence of
      receptors for IL-6 on the surface, and DNA synthesis of the cells was stimulated
      by the exogenous addition of recombinant human IL-6 into the culture medium. The
      cell growth was significantly inhibited in the presence of anti-human IL-6
      antibody in the culture medium. These findings indicate that IL-6 is one of the
      autocrine growth factors of this cell line in vitro.

PMID- 7827298
TI  - Effect of oral zinc supplementation on metallothionein and superoxide dismutase
      concentrations in patients with inflammatory bowel disease.
AB  - Oxygen-derived free radicals may contribute to intestinal tissue damage in
      inflammatory bowel disease. The concentrations of metallothionein and superoxide
      dismutase, two copper and zinc containing proteins involved in the scavenging of
      free radicals; were previously found to be decreased in the intestinal mucosa of
      patients with this disorder. The plasma zinc concentration is often decreased
      also in these patients. Since zinc is reported to be an efficient inducer of
      metallothionein synthesis, and probably of superoxide dismutase, we evaluated the
      effect of oral zinc supplementation on metallothionein and superoxide dismutase
      levels in patients with inflammatory bowel disease. Fourteen patients with
      inactive to moderately active inflammatory bowel disease received oral zinc
      supplementation (300 mg zinc aspartate, equal to 60 mg elemental zinc per day)
      for 4 weeks in a placebo-controlled double-blind cross-over trial. The plasma
      zinc concentration of these patients was low at the start of the study (12.2 +/-
      1.7 mumol/L, P < 0.05), when compared to that of 22 healthy controls (13.6 +/-
      2.3 mumol/L), but increased (P < 0.05) towards the levels of controls during the
      supplementation period (13.3 +/- 2.5 mumol/L). The concentrations of
      metallothionein and superoxide dismutase in plasma and in erythrocytes did not
      change in relation to the supplementation. The metallothionein concentration in
      both inflamed and non-inflamed intestinal mucosa was slightly higher after zinc
      supplementation but the superoxide dismutase concentration in the tissue was not
      altered. The histological inflammation score of intestinal biopsies, plasma
      albumin levels, and the disease activity index of the patients did not change
      during the study.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7827299
TI  - Dissolution of pancreatic stones by oral trimethadione in patients with chronic
      calcific pancreatitis.
AB  - The effect of oral dissolution therapy for pancreatic stones was evaluated in
      patients with chronic calcific pancreatitis. The anti-epileptic agent
      trimethadione was given orally to 30 outpatients at a dose of 0.9-1.5 g daily. On
      plain X-ray films and CT scans of the abdomen, pancreatic stones began to be
      dissolved around 8 months of treatment, and diminished in size and number or
      disappeared in 21 patients (70%) during the mean follow-up period of 32 months.
      The effect of trimethadione treatment on dissolution of stones was not closely
      related to the aetiology of the disease, distribution and size of stones,
      previous history of surgical interventions, or the degree of pancreatic
      dysfunctions. In three patients who stopped this medication of their own accord,
      pancreatic stones re-increased or reappeared about 6 months later. During
      trimethadione treatment, impaired exocrine pancreatic function returned to normal
      in four of nine patients examined, and diabetes mellitus was well controlled by
      either diet therapy alone or oral hypoglycaemic agents in eight of 10 patients
      who did not need insulin before trimethadione treatment. Complete relief of pain
      was noted in 73% of patients during the treatment. Overall gains and no change in
      bodyweight were observed in 83% of patients. Mild photophobia was the most common
      side effect, but could be easily overcome by wearing sunglasses. No severe side
      effects were observed in the liver, kidney, blood or the eyeground. Pancreatic
      stones in 30 patients not treated with trimethadione neither disappeared nor
      diminished spontaneously. Trimethadione treatment may be a useful tool for
      chemical dissolution of pancreatic stones.

PMID- 7827300
TI  - Effect of dimethadione administered intravenously on pancreatic secretion in
      dogs.
AB  - In order to detect both pancreatic excretion of dimethadione (DMO), a weak
      organic acid, and the effect of pancreatic DMO on secretin-stimulated pancreatic
      secretion, DMO was given intravenously to dogs with pancreatic fistulae at a dose
      of 50, 100 and 200 mg/kg. DMO was promptly excreted into pancreatic juice; the
      concentration decreased exponentially as it did in plasma at the highest dose of
      the compound. At equilibrium of DMO between pancreatic juice and plasma, the DMO
      concentration in the juice depended directly on that in plasma; the juice/plasma
      concentration ratios for DMO exceeded 1.0, ranging from 1.7 to 2.1. Pancreatic
      DMO caused a small but significant decrease in the water, bicarbonate and sodium
      secretion at non-equilibrium, and in the bicarbonate secretion at equilibrium. A
      decrease in the bicarbonate secretion may result largely from the buffer action
      of bicarbonate on protons provided by the undissociated form of DMO. The sum of
      both bicarbonate and chloride concentrations in pancreatic juice decreased with
      the increased DMO concentration in the juice, implying that DMO may compete with
      the secretion of bicarbonate and/or chloride across the apical membrane of the
      duct cell. Pancreatic DMO can act as a non-specific inhibitor of pancreatic water
      and electrolyte secretions.

PMID- 7827301
TI  - A correlative study on the mechanism of adaptive cytoprotection against ethanol
      induced gastric lesion formation in rats.
AB  - The protective effect of mild irritants against the subsequent gastric injury
      induced by necrotizing agents has been termed 'adaptive cytoprotection'. In this
      study, the possible pathway and mechanisms of adaptive cytoprotection induced by
      20% ethanol were investigated. An ex-vivo gastric chamber preparation was used.
      The gastric mucosa was exposed to 20% ethanol before subsequent administration of
      100% ethanol 15 min later. Subdiaphragmatic vagotomy or drug pretreatment was
      carried out in order to elucidate the mechanisms of adaptive cytoprotection by
      20% ethanol. The results showed that 20% ethanol pre-exposure significantly
      protected the gastric mucosa against damage caused by 100% ethanol. This
      protective action was completely abolished by atropine or lidocaine pretreatment,
      whereas vagotomy and hexamethonium failed to have a significant influence. The
      cytoprotective effect, however, was independent of the gastric secretory volume,
      titratable acid content, luminal soluble mucus level and gastric mucosal blood
      flow. Exposure of only half the gastric mucosa to the mild irritant resulted in
      the protection of both sides of the mucosa. All these findings indicate that the
      adaptive cytoprotection of 20% ethanol involves the participation of
      chemoreceptors and muscarinic receptors in the gastric mucosa. An internal
      enteric reflex arc, with transmission of signals within the gastric mucosa, may
      also contribute to the cytoprotective process of the mild irritant.

PMID- 7827302
TI  - Prevalence of Helicobacter pylori in southern Indian controls and patients with
      gastroduodenal disease.
AB  - The spiral organism Helicobacter pylori has been causally implicated in the
      genesis of various gastroduodenal diseases. Since these diseases are common in
      southern India, this study was undertaken to determine the prevalence of H.
      pylori in the gastric mucosa of asymptomatic adults and patients with various
      gastroduodenal diseases. H. pylori was detected in the gastric mucosa of 25 of 30
      (83.3%) normal volunteers. Prevalence rates in the disease groups were also high,
      and included 38 of 41 patients with duodenal ulcer (92.6%), 13/16 with gastric
      ulcer (81.3%), and 85/119 subjects (71.4%) with non-ulcer dyspepsia. Light
      microscopic examination of the gastric mucosa provided the best method of
      detecting H. pylori. H. pylori colonization was significantly associated with
      histological abnormalities, mainly chronic atrophic gastritis (147) and
      superficial gastritis (11), while only three of 161 H. pylori positive patients
      had histologically normal antral mucosa. Ultrastructural examination revealed
      changes in the apical complex of the gastric mucosal cells in response to
      bacterial adhesion, with mucus depletion and cellular damage. Bacteria were also
      noted disrupting the tight junctions and entering the intercellular spaces. The
      high prevalence of H. pylori infection may explain the high incidence of
      gastritis, duodenal ulceration and gastric carcinoma in this population. However,
      in this population, the prevalence of infection in asymptomatic individuals was
      nearly as high as that in duodenal ulcer, underlining the need for further study
      to identify the differences in host response or bacterial pathogenicity that lead
      to the development of ulcer in only some individuals.

PMID- 7827303
TI  - Colonization by Helicobacter pylori and its relationship to histological changes
      in the gastric mucosa in portal hypertension.
AB  - In order to investigate the relationship between Helicobacter pylori infection of
      the gastric mucosa and mucosal changes in portal hypertension, gastric fundic and
      antral biopsies were obtained from 66 patients with portal hypertension and 49
      controls with non-ulcer dyspepsia (NUD). Gastric mucosa from portal hypertensive
      patients exhibited typical vascular dilatation and congestion, while mild
      dilatation of lamina propria blood vessels was not uncommon in NUD patients with
      histological evidence of gastritis. Colonization of the gastric mucosa by H.
      pylori infection was significantly less in portal hypertension (51.5%) compared
      to controls (75.5%; P < 0.01). The difference was more apparent in patients with
      marked vascular dilatation (18.8% colonization) compared to patients with minimal
      vascular dilatation (66.7%). H. pylori infection was significantly associated
      with active superficial gastritis (P < 0.001), and with atrophic gastritis (P <
      0.001), in both study groups. H. pylori-negative superficial gastritis was
      significantly more common in portal hypertension (25/66 patients) than in
      controls (7/49; P < 0.05). H. pylori infection was not more common in patients
      who had undergone repeated sclerotherapy. The results suggest that the gastric
      mucosa of portal hypertension does not provide a hospitable environment for H.
      pylori colonization, particularly when mucosal congestion is marked. H. pylori
      infection does not add significantly to the gastropathy of portal hypertension.

PMID- 7827304
TI  - Gastric cytoprotection by amoxycillin in the rat.
AB  - Amoxycillin in combination with anti-ulcer agents has been shown to prolong
      duodenal ulcer remission. While this effect can be related to the eradication of
      Helicobacter pylori, it is not known if amoxycillin might possess cytoprotective
      properties. Protection against ethanol-induced gastric mucosal damage by
      intragastric instillation of amoxycillin suspension (prepared from capsule form)
      and solution (from injection form, 100% pure amoxycillin), and by intraperitoneal
      injection of amoxycillin solution was studied using an ex vivo gastric chamber in
      the rat. Intragastric and intraperitoneal administration of amoxycillin dose
      dependently protected the rat gastric mucosa from damage by absolute ethanol.
      This protection was lost when the rats were pretreated with indomethacin. Gastric
      mucosal blood flow as measured by laser Doppler flowmetry and gastric acid output
      were unaffected by amoxycillin. Amoxycillin imparts gastric cytoprotection, and
      one possible mechanism is by the release of prostaglandins.

PMID- 7827305
TI  - Inflammatory bowel disease, free radicals and zinc.

PMID- 7827306
TI  - Oral contraceptive-dependent growth of focal nodular hyperplasia.
AB  - A 22 year old woman was incidentally found to have a hepatic small haemangioma
      like mass, measuring 1.4 cm in diameter, by an ultrasonographic examination. The
      mass demonstrated no change in size or appearance for 6 months until the patient
      began to take oral contraceptives. Eventually, the mass increased to 2.0 cm in
      diameter after using oral contraceptives for 6 months. A histological examination
      suggested the mass to be typical focal nodular hyperplasia, and not hepatic
      adenoma. There was no further change in either size or appearance in the ensuing
      1 year after the discontinuation of oral contraceptives.

PMID- 7827307
TI  - Nutritional support through percutaneous transhepatic internal drainage route in
      common bile duct cancer.
AB  - A 69 year old female with a duodenal bulb obstruction due to direct invasion of
      common bile duct cancer who received total enteral nutrition through the route of
      percutaneous transhepatic internal drainage (PTID) was presented. The tip of PTID
      tube was placed over the duodeno-jejunal flexure. Jejunal infusion of all
      nutrients and the bile juice through this route kept her in good nutritional
      condition until the terminal stage of primary disease. This procedure did not
      cause the infection of the biliary system. Major problems, tube obstruction and
      diarrhoea, were easily resolved with the selection of an appropriate infusion
      schedule and nutrient concentration. We conclude that nutritional support through
      the PTID route is a beneficial means for compromised patients without laparotomy
      or hospitalization.

PMID- 7827308
TI  - Thrombocytopenia associated with platelet-associated immunoglobulin G in
      alcoholic hepatitis.
AB  - A 45 year old Japanese man with alcoholic hepatitis developed thrombocytopenia
      together with an increase in the level of platelet-associated immunoglobulin G
      (PAIgG). Bone marrow aspiration revealed a normal nucleated cell count and a
      slight increase of megakaryocytes. After abstinence from alcohol, laboratory and
      symptomatic improvement occurred in association with a prompt increase in the
      platelet count and a corresponding decrease of PAIgG. These findings suggest that
      PAIgG may have been involved in the development of thrombocytopenia in this
      patient.

PMID- 7827309
TI  - Octreotide therapy for pancreaticopleural fistula.
AB  - Pancreaticopleural fistula is a rare but remediable complication of pancreatitis.
      Hitherto, treatment by means of total parenteral nutrition and thoracocentesis
      had resulted in an overall success rate of 40% only. Surgical obliteration of
      persistent fistulae is required in many cases, as the underlying pancreatic duct
      lesion often prevents spontaneous closure of the fistula. We report a patient
      suffering from pancreaticopleural fistula with a tightly strictured pancreatic
      duct. The fistula was successfully obliterated with the use of octreotide
      addition to thoracocentesis and total parenteral nutrition. Pancreatic bypass
      surgery was later performed only for pain relief. We believe that octreotide can
      effectively suppress pancreatic secretion and promote closure of
      pancreaticopleural fistula even in the presence of severe pancreatic duct
      lesions. Thus the risk of infection and early surgery for persistent fistula can
      be minimized.

PMID- 7827310
TI  - Gastrointestinal bleeding from hepatocellular carcinoma invading the stomach.
AB  - Bleeding from hepatocellular carcinoma (HCC) invading the gastrointestinal tract
      is very uncommon. We report the case of a 61 year old man who had a large bleed
      from HCC invading the fundus of the stomach. Diagnosis was eventually made at
      laparotomy and he is still alive 7 months after local resection.

PMID- 7827311
TI  - Cortical CSF volume fluctuations by MRI in brain aging, dementia and
      hydrocephalus.
AB  - Dynamic MR imaging has revealed dramatic fluctuations in the appearance of CSF in
      the cortical sulci and cortical subarachnoid spaces in aging individuals and
      patients with hydrocephalus, dementia and Down syndrome in contrast to young
      healthy volunteers. The changes have been interpreted as volume fluctuations that
      represent undamped CSF hydrodynamics and have implications with respect to the
      origin of CSF in the cortical regions and with respect to the similarity between
      aging and dementia and edematous states of the brain.

PMID- 7827312
TI  - Limbic cortical influences to the vagal input neurones of the solitary tract
      nucleus.
AB  - In acute experiments on cats, electrical stimulation of the anterior limbic
      cortex was shown to modulate activity of vagal input neurones of the nucleus of
      the tractus solitarius. In the majority of the solitary tract nucleus neurones
      the responses induced by electrical stimulation of the vagus were depressed by
      the stimulation of anterior limbic cortex. Under these conditions the patterns of
      responses or their latency were changed. Our results are discussed with respect
      to possible mechanisms for cortical control of sensory transmission in the
      nucleus of the tractus solitarius.

PMID- 7827313
TI  - Disturbances in blood pressure homeostasis modify GABA release in the locus
      coeruleus.
AB  - The locus coeruleus (LC) of anaesthetized rats was superfused with artificial
      cerebrospinal fluid through a push-pull cannula and the release of the amino
      acids gamma-aminobutyric acid (GABA), taurine and arginine was determined in the
      superfusate. Increases in blood pressure (BP) induced either by intravenous
      infusions of noradrenaline and phenylephrine or by blood injection enhanced the
      release of GABA in the LC. Decreases in BP elicited by intravenous infusion of
      sodium nitroprusside or by haemorrhage decreased the GABA release rate. The BP
      changes did not influence the release rates of taurine and arginine. These
      findings demonstrate that GABA release in the LC is modified by cardiovascular
      impulses and suggest that GABAergic neurones modulate LC activity in response to
      disturbances in BP homeostasis.

PMID- 7827314
TI  - Spatial learning following posterior parietal or hippocampal lesions.
AB  - Rats with either posterior parietal (PPC) or dorsal hippocampal (HIP) lesions
      were tested for open-field activity, acquisition of a multiple T water maze
      habit, and presence of a 'cognitive map' of the water maze arena. The
      performances of control and PPC-lesioned rats were similar on all behavioral
      measures. However, the HIP-damaged rats demonstrated higher levels of general
      activity, severe deficits in both working and reference memory in the multiple T
      water maze task, and failed to develop a cognitive map of the water maze arena.

PMID- 7827315
TI  - Audio-vocal learning in a non-human mammal: the lesser spear-nosed bat
      Phyllostomus discolor.
AB  - In the course of development, pups of the neotropical bat Phyllostomus discolor
      seem to adapt their isolation calls to the vocal signature of their mother's
      directive calls. Under controlled experimental conditions however, audio-vocal
      learning so far has not been demonstrated in any terrestrial mammal except man.
      In the present study one group of bat pups was hand-reared in the absence of
      conspecific vocalizations, whereas an unvarying, digitally stored maternal
      directive call was repeatedly presented to the juveniles of a second group prior
      to each feeding. In contrast to the unstimulated controls, the animals of the
      playback group adapted their isolation call structure to this external acoustic
      reference signal.

PMID- 7827316
TI  - Recognition memory in 3- to 4-day-old human neonates.
AB  - It has been recently established in both adult monkeys and humans that visual
      recognition memory, as assessed with a preferential visual fixation technique,
      depends on the integrity of the neural structures situated in the medial part of
      the temporal lobe. This kind of memory has been observed in infant monkeys not
      earlier than day 15. Using a familiarization technique we established that this
      recognition memory is present in human infants as early as postnatal day 3 when a
      2-min retention interval is used. This visual recognition memory might be
      controlled by subcortical structures. The possibility that the medial temporal
      structure involved in adult visual memory is operating at birth cannot, however,
      be ruled out.

PMID- 7827317
TI  - Sensorimotor gating deficit after lesions of the superior colliculus.
AB  - The superior colliculus (SC) is important for the processing of sensory
      information of different modalities and for the mediation of adequate motor
      responses in mammals. The present study investigated the effects of excitotoxic
      lesions of the SC on two different modulations of the acoustic startle response
      (ASR) in rats. Modulations of the ASR (i.e. increase or decrease of the response
      strength) represent useful models for the study of sensorimotor integration
      phenomena. Lesions of the SC decreased the prepulse inhibition of the ASR without
      affecting the baseline startle amplitude or the enhancement of the ASR by
      footshock sensitization. These results suggest a crucial role of the SC in the
      prepulse inhibition of the ASR, a model of sensorimotor gating.

PMID- 7827318
TI  - Synergistic control by androgens and estrogens of aromatase in the quail brain.
AB  - Castrated quail were injected with testosterone or with the synthetic hormones
      diethylstilbestrol (DES) or methyltrienolone (R1881) to analyse the steroid
      specificity in the induction of brain aromatase. R1881 produced a moderate
      (generally non-significant) increase in the number of aromatase-immunoreactive
      cells. DES significantly increased the number of positive cells in most brain
      areas. A clear synergism between DES and R1881 was observed in all brain regions:
      more immunoreactive cells were found in birds receiving both compounds than in
      those injected with DES or R1881 alone. DES and R1881 are highly specific ligands
      for oestrogen and androgen receptors respectively. It appears likely that both
      androgens and oestrogens directly modulate brain aromatase, presumably at the
      transcription level.

PMID- 7827319
TI  - Reduced N-acetylaspartate concentration in temporal lobe epilepsy by quantitative
      1H MRS in vivo.
AB  - We used proton magnetic resonance spectroscopy (1H MRS) to determine
      concentrations of N-acetylaspartate (NAA), creatine and choline in vivo (63 MHz)
      and in vitro (400 MHz) in seven patients undergoing surgical treatment of
      intractable temporal lobe epilepsy (TLE). Nine healthy volunteers were used as
      controls for in vivo MRS. NAA concentrations in vivo on the ipsilateral and
      contralateral sides were 6.5 +/- 1.3 (s.d.) and 7.9 (+/- 2.1) mmol l-1,
      respectively and 8.6 (+/- 0.8) mmol l-1 in the volunteers. NAA concentration in
      vitro was 3.2 (+/- 0.9) mumol g-1 wet weight (ww) and the corresponding
      concentration from the macroscopically intact brain tissue was 4.7 (+/- 1.0)
      mumol g-1 ww. Thus, in vivo quantitative 1H MRS identified the size of seizure
      focus in patients with temporal lobe epilepsy.

PMID- 7827320
TI  - Are glia among the cells that express immunoreactive c-Fos in the suprachiasmatic
      nucleus?
AB  - Light physiologically regulates the levels of c-Fos in the suprachiasmatic
      nucleus (SCN), but the identity of most of the cells that express this DNA
      binding protein is unknown. To determine whether SCN c-Fos expression is
      restricted to neurons, we performed light microscopic double-label
      immunohistochemistry on sections of rat SCN using two c-Fos antibodies in
      conjunction with antibodies to neurofilament and S-100 proteins (as markers of
      neuronal and astrocytic cell bodies, respectively). In addition to c-Fos labeled
      nuclei in neurons, we found a small population of labeled nuclei in glial cell
      bodies. These observations suggest that c-Fos is expressed in a heterogeneous
      cell population in the SCN and that its function in circadian clock mechanisms
      may be cell specific.

PMID- 7827321
TI  - Sodium/calcium exchanger in olfactory receptor neurones of Xenopus laevis.
AB  - Ca2+ ions enter neurones through various types of calcium and cation channels.
      The mechanisms by which Ca2+ ions are spatially buffered and expelled from
      neurones have been studied considerable less. Using calcium imaging in
      conjunction with the patch clamp technique, we investigated the Na/Ca exchanger
      in olfactory neurones and found evidence for its localization on the dendrite. It
      is suggested that this tends to decouple increases in [Ca2+]i occurring in the
      transduction compartments of the cell from processes in the soma.

PMID- 7827322
TI  - Fluoxetine effects on cerebral glucose metabolism.
AB  - In a counterbalanced, double-blind, placebo-controlled trial, 40 mg of fluoxetine
      was administered to four healthy adult volunteers (three men, one woman; age
      range 20-39 years), 90 min before injection of 6-7.5 mCi of [18F]-2-deoxyglucose
      to measure cerebral metabolic rate of glucose (CMRglu). Subjects were engaged in
      a visual monitoring task shortly before and during scanning with a PETT-VI
      tomograph. Global CMRglu did not differ when placebo (8.93 +/- 0.96 mg 100 g-1
      min-1) was compared to fluoxetine (8.22 +/- 0.86 mg 100 g-1 min-1; paired t-test
      = 0.82, df = 3, p < 0.48). However, statistical parametric mapping of differences
      in CMRglu between placebo and fluoxetine conditions revealed regional effects of
      fluoxetine shown by decreased metabolism in the amygdaloid complex, hippocampal
      formation and ventral striatum, and by increased metabolism centered in the right
      superior parietal lobe (Brodmann area 7). Parametric mapping for use in PET
      studies of glucose metabolism represents a significant new tool for studying drug
      effects in humans.

PMID- 7827323
TI  - DNA synthesis is induced in adult neurons after expression of E2F1 and E1A.
AB  - Differentiated neurons in several brain regions express the retinoblastoma (Rb)
      tumor suppressor gene. Changing the tumor suppressor function of Rb by expressing
      transcription factor E2F1 and viral oncoprotein E1A in cerebellar granular
      neurons in vitro and in cerebral cortical neurons in vivo results in the
      induction of DNA synthesis in these neurons. Immunoliposome-mediated transfection
      of E1A and E2F1 cDNAs into the adult cortical neurons of rats in vivo results in
      initiation of DNA synthesis in 5-15% of the transfected neurons. These results
      indicate that expression of Rb may be necessary to prevent induction of
      differentiated neurons to proliferate since many mitogenic growth factors are
      expressed in the brain.

PMID- 7827324
TI  - Expression of 9-O-acetylated gangliosides during development of the rat olfactory
      system.
AB  - The expression of 9-O-acetylated gangliosides recognized by the Jones monoclonal
      antibody (mAb) correlates with cell migration and axonal outgrowth in the
      developing rat nervous system. We studied the expression of these gangliosides
      during the development and maturation of the rat olfactory system. Beginning on
      embryonic day 13 (E13) the olfactory epithelium and the migratory mass were
      intensely stained with Jones mAb. However, though this immunoreactivity
      disappeared from the olfactory epithelium at E19, it remained in a few fascicles
      and some glomeruli of the newborn and adult olfactory bulbs. We concluded that
      the expression of 9-O-acetylated gangliosides by olfactory axons and/or migrating
      cells may facilitate axonal outgrowth during development and might be involved in
      the formation of new glomeruli in the mature olfactory bulb.

PMID- 7827325
TI  - Effects of metabotropic glutamate receptor activation on the cellular and network
      level in the lamprey spinal cord.
AB  - The effects of the metabotropic glutamate receptor (mGluR) agonist ACPD ((1S,3R)
      1-aminocyclopentane-1,3-dicarboxylic acid) on single neurones and on the network
      underlying locomotion in the lamprey have been analysed. ACPD induces a
      depolarization in lamprey spinal cord neurones, which is insensitive to
      tetrodotoxin (TTX) and ionotropic glutamate receptor antagonists, but is
      reversibly blocked by the mGluR antagonist MCPG ((+)-alpha-methyl-4
      carboxyphenylglycine). The ACPD-induced depolarization persists in a calcium-free
      solution or when the calcium channel blocker cadmium is added to the solution. At
      the network level ACPD causes an increased burst frequency during fictive
      locomotion by increasing the excitability level of network neurones.

PMID- 7827326
TI  - Subtypes of NMDA receptor in neurones cultured from rat brain.
AB  - The non-competitive N-methyl-D-aspartate (NMDA) antagonist, ifenprodil,
      discriminates two receptor populations, each of which shows a reciprocal
      abundance in cultured cortical and cerebellar granule cells. Thus approximately
      70% of NMDA-gated membrane current was antagonized with high affinity (IC50 = 1.4
      +/- 0.9 microM) in cortical neurones whereas only approximately 20% was
      antagonized with high affinity (IC50 = 1.3 +/- 0.3 microM) in granule cells.
      Inhibition curves for CGS 19755 appeared relatively monophasic: this competitive
      NMDA antagonist had a significantly higher affinity for the granule cell receptor
      (Ki = 0.8 +/- 0.2 microM) compared with that on cortical neurones (Ki = 2 +/- 0.6
      microM). The data suggest that these two antagonists may be of value in
      identifying the expression of subpopulations of native NMDA receptors in other
      brain regions.

PMID- 7827327
TI  - Anti-inflammatory drugs suppress injury-induced NADPH-d activity in CA1 pyramidal
      neurones.
AB  - Inducibility of NADPH-diaphorase (NADPH-d) or nitric oxide synthase (NOS) has
      been demonstrated in pyramidal neurones of the hippocampus, but the mechanisms of
      this induction are not known. The present study aimed to assess the role of anti
      inflammatory drugs in injury-induced production of NADPH-d/NOS in CA1 pyramidal
      neurones. We found that either a steroid, dexamethasone or a non-steroid,
      indomethacin, prevents induction of these enzymes. We also found that NO is not
      necessary for the induction. None of the three drugs used had detectable effect
      on the neurones which contain constitutive NADPH-d/NOS.

PMID- 7827328
TI  - Interactive and discontinuous long-lasting potentiation in the dentate gyrus.
AB  - Non-overlapping applications of l-isoproterenol, a beta-adrenergic agonist, and
      the neuropeptide cholecystokinin 8-S produce long-lasting potentiation of evoked
      action potentials in the dentate gyrus. There is no corresponding modification of
      excitatory post-synaptic potentials. This effect, referred to as interactive long
      lasting potentiation, is pharmacologically similar to the long-lasting
      potentiation produced by discontinuous or non-overlapping applications of l
      isoproterenol. Metoprolol or propranolol, both beta-adrenergic antagonists,
      prevent interactive long-lasting potentiation, but D-amino-5-phosphonopentanoic
      acid, an N-methyl-D-aspartate receptor antagonist, does not. Cholecystokinin 8-S
      and beta-adrenergic receptors may activate a common intermediate in the
      interactive paradigm.

PMID- 7827329
TI  - Nigral dopaminergic cell loss in vitamin E deficient rats.
AB  - alpha-Tocopherol concentrations in brain were reduced to 3% of control levels in
      rats fed a vitamin E deficient diet for 52 weeks. Vitamin E deficiency resulted
      in a 19-33% loss of tyrosine hydroxylase (TH) immunopositive neurones in the
      substantia nigra, but not in the adjacent ventral tegmental area, compared with
      controls. Vitamin E deficiency, however, did not reduce striatal dopamine
      concentrations or turnover. When antioxidant defence mechanisms are defective, as
      in chronic vitamin E deficiency, the nigrostriatal pathway may be affected by
      oxidative damage and this may have implications for Parkinson's disease.

PMID- 7827330
TI  - Activation of acetylcholinesterase by aluminium(III): the relevance of the metal
      species.
AB  - The present paper reports how aluminium [Al(III)] at a concentration of 3.7
      microM can activate the bovine erythrocytic enzyme acetylcholinesterase (AChE) by
      about 38% in vitro. This same activating effect was observed on AChE form human
      as well as from rat erythrocyte ghosts and murine neuroblastoma cells. The
      interaction between Al3+ and gamma-peripheral sites of the enzyme produces AChE
      structural modifications as evidenced by circular dichroism measurements. This
      may provide a molecular explanation of the raised enzymatic activity.

PMID- 7827331
TI  - Cholinergic denervation of the rat hippocampus by 192-IgG-saporin:
      electrophysiological evidence.
AB  - The consequences of intracerebroventricular injection of the toxin 192-IgG
      saporin on the electrophysiological properties of CA1 pyramidal cells were
      investigated using intracellular recordings in the in vitro hippocampal slice
      preparation. We present the first electrophysiological evidence of a dysfunction
      of hippocampal cholinergic afferents following injection of 192-IgG-saporin. The
      synaptic events mediated by acetylcholine were altered in such animals: the slow
      cholinergic excitatory postsynaptic potentials as well as the cholinergic
      activation of GABAergic interneurones were dramatically depressed or even absent;
      the amplitude and duration of the afterhyperpolarization following a burst of
      spikes were increased, while other neuronal properties were not modified. These
      specific alterations suggest that the toxin 192-IgG-saporin is a specific tool
      for the experimental study of cholinergic denervation in the hippocampus.

PMID- 7827332
TI  - Brain regional serotonin synthesis following adaptation to repeated restraint.
AB  - A single 2 h episode of restraint stress decreased food intake and growth rate of
      rats. These deficits were not observed after five restraint periods of 2 h a day,
      suggesting that adaptation occurred. An acute challenge with 2 h restraint
      increased 5-hydroxytryptamine (5-HT) synthesis rate in the cortex, hypothalamus,
      midbrain and hindbrain of previously unrestrained rats, but not those adapted to
      5 days of 2 h daily restraint. Hippocampal and striatal 5-HT synthesis was not
      increased significantly by 2 h restraint in previously unrestrained rats but was
      increased and decreased, respectively, in rats exposed to five 2 h daily
      restraints, when they were restrained on the sixth day. The findings suggest an
      important role of 5-HT particularly in the hippocampus, in adaptation to stress.

PMID- 7827333
TI  - Glycolysis can prevent non-synaptic excitatory amino acid release during hypoxia.
AB  - Release of excitatory amino acids (EAAs) contributes to neuronal death during
      cerebral ischemia. EAA release occurs by both synaptic and non-synaptic
      mechanisms. However, studies in vivo yield conflicting estimates of their
      relative importance. This disparity may reflect differing degrees of substrate
      deprivation produced by various in vivo models. We used primary rat astrocyte
      cultures to establish the relationship between substrate deprivation, energy
      failure, and non-synaptic EAA release. Combined hypoxia and glycolytic blockade
      produced severe ATP depletion and EAA release (10-fold). In contrast, hypoxia
      alone caused only a moderate reduction in ATP and did not induce EAA release.
      These findings suggest that glycolytic metabolism may be an important factor
      affecting the magnitude of non-synaptic EAA release during ischemia.

PMID- 7827334
TI  - RU24722 induces spatially organized phenotypic plasticity in the locus coeruleus.
AB  - The plasticity of tyrosine hydroxylase (TH) expression in rat locus coeruleus
      (LC) was evaluated after RU24722 TH induction using, as a new parameter of
      characterization, the quantitative topology of LC defined by TH-positive cells.
      This new phenotype was spatially organized into cell subpopulations in the medial
      LC, dorsal and ventro-lateral to the initial perikaryal space. Reserpine and
      parachlorophenylalanine, which elicited a similar increase in the TH content,
      failed to induce a significant change in the number of TH-expressing cells.
      Activation of TH expression is not sufficient to reveal the existence of such a
      plasticity and some original but still unknown mechanism(s) of control of TH
      expression is affected by RU24722.

PMID- 7827335
TI  - U-69593 prevents cocaine sensitization by normalizing basal accumbens dopamine.
AB  - Repeated intermittent administration of cocaine (20 mg kg-1, i.p.) for 3 days
      dramatically increased basal dopamine (DA) overflow in the nucleus accumbens
      (ACB) 48 h after the final daily injection. This cocaine pretreatment also
      produced a significant increase in stereotypy in response to a subsequent cocaine
      challenge. However, when the selective kappa-opioid receptor agonist U-69593 was
      administered in combination with cocaine for 3 days, these cocaine-induced
      biochemical and behavioral effects were abolished. It is suggested that the
      responsiveness of mesolimbic DA neurons to cocaine is intimately related to basal
      DA concentrations within the ACB and that U-69593, by normalizing cocaine-induced
      increases in basal DA overflow, may prevent the development of behavioral
      sensitization to cocaine.

PMID- 7827336
TI  - Evidence for vesicular storage of glutamate in primary afferent terminals.
AB  - The correlation between the density of gold particles signalling fixed glutamate
      and the density of synaptic vesicles was examined in primary afferent terminals
      in the rat dorsal horn. Statistically significant positive correlations between
      these parameters were found in lamina I and III-V primary afferent terminals,
      identified through axonal transport of choleragenoid-horseradish peroxidase
      conjugate, and in lamina II dense sinusoid axon terminals of presumed thin
      calibre primary afferent origin. Profiles containing pleomorphic synaptic
      vesicles displayed negative or statistically insignificant correlations between
      the density of synaptic vesicles and that of gold particles. These observations
      indicate that primary afferent terminals store glutamate in synaptic vesicles and
      provide further evidence for a role of glutamate as a primary afferent
      neurotransmitter.

PMID- 7827337
TI  - Expression of alpha and beta thyroid receptors during oligodendrocyte
      differentiation.
AB  - To determine which thyroid receptor (TR) isoforms are expressed during
      oligodendrocyte differentiation, we studied the expression of the mRNAs encoding
      two alpha (alpha 1 and alpha 2) and one beta (beta 1) TR isoforms in a
      bipotential oligodendrocyte-type 2-astrocyte (O-2A) progenitor cell line (CG-4)
      as well as in rat O-2A progenitor cells and oligodendrocytes. O-2A progenitor
      cells expressed only TR alpha-mRNAs, whereas oligodendrocytes and type 2
      astrocytes also expressed TR beta 1-mRNAs. The differential expression of alpha 1
      and beta 1 TRs suggests specific functions for both types of TRs during
      oligodendrocyte differentiation. We present evidence for a possible role of TR
      alpha 1 in the effect of thyroid hormones on the proliferation of CG-4 cells
      maintained as progenitor cells.

PMID- 7827338
TI  - Ontogeny of tyrosine hydroxylase levels in the neuropil close to locus caeruleus.
AB  - We aimed to characterize tyrosine hydroxylase (TH) expression within the
      pericaerulean area (PCA) during postnatal development. Levels of TH along the
      caudorostral axis of the locus caeruleus (LC) showed a dramatic increase in the
      PCA beyond day 21. This was due to the extension of the TH-containing area,
      particularly organized in the ventrolateral and longitudinal directions. As
      dendrites of LC neurones were observed at long distances within this PCA, such an
      increase in TH distribution could affect functions related to the LC.

PMID- 7827339
TI  - Cesium prevents maintenance of long-term depression in rat hippocampal CA1
      neurons.
AB  - Long-term depression of field excitatory postsynaptic potentials (EPSP) in the
      CA1 region of hippocampal slices was evoked by delivering a 15 min train of
      pulses at 1 Hz to the Schaffer-commissural-CA1 pathway, and prevented by adding
      an N-methyl-D-aspartate (NMDA) receptor antagonist (AP-5, 50 microM) to the
      perfusing medium. Superfusion of the slices with Cs (2 mM) during the 1 Hz
      stimulation period could both inhibit the maintenance phase of the depression
      itself and elicit spontaneous rhythmic activity. Cs had no effect on the
      postsynaptic response to the GABA-B agonist, baclofen. As a major effect of Cs is
      a block of the hyperpolarization-activated current (Ih), these results suggest
      the possible involvement of Ih in the maintenance of long-term depression.

PMID- 7827340
TI  - Generalized presence of a PEC-60-like peptide in catecholamine neurones.
AB  - PEC-60, a 60-residue intestinal peptide structurally related to the pancreatic
      secretory type of trypsin inhibitor, has been isolated, characterized and
      molecularly cloned. It shows biological activity as a hormone in both the
      gastrointestinal tract and in the immune system. We now report
      immunohistochemical evidence suggesting its neural localization exclusively
      within central and peripheral catecholamine (CA) neurones. PEC-60-like
      immunoreactivity was present in cell bodies, dendrites and nerve terminals of
      virtually all catecholamine neurones examined and including the noradrenergic
      gland cells of the adrenal medulla. PEC-60-like immunoreactivity was not seen,
      however, within the tyrosine hydroxylase-positive but CA-negative arcuate
      neurones producing growth hormone releasing hormone. The findings open up the
      possibility that a PEC-60-like peptide may represent a generalized co-transmitter
      in the peripheral and central CA neurones.

PMID- 7827341
TI  - Amyloid deposits and loss of neurones in the claustrum of the aged dog.
AB  - In dogs under 17 years of age no amyloid deposits were observed in the claustrum.
      After that age amyloid deposits were found in all the brains studied. The number
      of amyloid deposits increases rapidly between 17 and 19 years of age. In none of
      the animals were neurofibrillary tangles found. However, in almost all claustra
      with amyloid deposits the number of neurones was smaller than in those without
      amyloid pathology. The loss of neurones resulted in a decrease in the volume of
      claustrum, which is about 22% smaller in dogs over 17 years of age than in
      younger animals. No considerable age-related differences were found in the
      average size of neurones and their nuclei.

PMID- 7827342
TI  - Induction of LTD but not LTP through metabotropic glutamate receptors in visual
      cortex.
AB  - Long-term potentiation (LTP) and long-term depression (LTD), often used as
      essential components in synaptic models for learning, memory and forgetting, can
      be produced in cortical tissue by repetitive activation of neural pathways under
      different stimulus conditions. The involvement of metabotropic glutamate
      receptors (mGluRs) has been postulated to be necessary for the establishment of
      either or both forms of synaptic plasticity in hippocampus. The recent
      introduction of a specific antagonist for mGluRs, (+/-)-alpha-methyl-4
      carboxyphenylglycine, prompted the investigation of the respective involvement of
      this receptor population in the induction of LTP and LTD in visual cortex of the
      rat in vitro. The results suggest the critical involvement of mGluRs in producing
      LTD but not LTP.

PMID- 7827343
TI  - Opioid modulation of oxytocin release from spinal cord synaptosomes.
AB  - Regulation of oxytocin release from spinal cord synaptosomes was investigated
      using in vitro preparations. Experiments were designed to determine whether
      opioid peptides regulate oxytocin release from spinal cord synaptosomes, as they
      do from synaptosomes derived from neurohypophysis. Oxytocin release was evoked by
      the addition of 56 mM KCl in synaptosomes prepared from thoracic and lumbosacral
      parts of the spinal cord. Addition of 5 microM naloxone, 1 min prior to the
      addition of the stimulus, caused a significant (p < 0.025) increase of oxytocin
      release. Prior addition of 5 microM dynorphin, demonstrated a significant (p <
      0.01) decrease whereas addition of 5 microM [D-Ala2,N-Me-Phe4,Gly-ol]-enkephalin
      showed no effect on KCl-induced OT release. The results suggest that spinal cord
      OT release is under inhibitory control of opioid peptides and the opioids act via
      the kappa opioid receptor.

PMID- 7827344
TI  - Characterization of dopamine receptor binding sites in the subthalamic nucleus.
AB  - Experiments were undertaken to determine the distribution and binding profile of
      dopamine (DA) receptors within a key extra-striatal region of the rat basal
      ganglia, the subthalamic nucleus (STh). Analysis of [125I]NCQ-298 autoradiograms
      showed that binding sites of the D2-receptor family are abundant in the STh.
      Competition studies indicated that these sites were specifically of the D2
      subtype. However, contrary to previously published data, [125I]SCH-23982
      autoradiograms failed to reveal D1 receptor binding in the STh. These data
      suggest that DA acting at D2 receptors may directly modulate STh neural activity
      and furthermore that the antagonism of STh D2 receptor binding by neuroleptics
      may be involved in the expression of extrapyramidal motor disturbances.

PMID- 7827345
TI  - Apomorphine suppresses ingestive behaviour in chronic decerebrate rats.
AB  - To determine whether dopamine receptors in the brain stem can mediate inhibition
      of feeding behaviour male rats in which the forebrain was disconnected from the
      brain stem were studied. Such decerebrate rats do not approach food but display
      ingestive responses if infused intraorally with a 1 M solution of sucrose at 0.6
      ml min-1. Intraperitoneal injection of 5 micrograms cholecystokinin octapeptide,
      a physiological satiety peptide, or 400 micrograms apomorphine, a dopamine D1-D2
      receptor agonist, suppressed intake of the sucrose solution. The results support
      a role of brain stem dopamine receptors in the control of ingestive behaviour.

PMID- 7827346
TI  - Co-localization of NADPH-diaphorase and myomodulin in synaptic glomeruli of
      Aplysia.
AB  - We used NADPH-diaphorase staining as a marker for nitric oxide synthase to
      identify neurons and synapses in the nervous system of the mollusc Aplysia
      californica in which nitric oxide may be used as a transmitter. About 30
      bilaterally paired neurons in the cerebral ganglion and a few neurons in other
      major ganglia were stained, as well as specific fiber tracts, neuropil and the
      lateral terminus, a synaptic glomerulus of the optic tract. The glomerulus was
      also stained by antisera to myomodulin, a peptide co-transmitter. The co
      localization of myomodulin immunoreactivity and NADPH-diaphorase staining in the
      synaptic glomerulus, and the staining of select neurons and synaptic structures
      strongly suggests that nitric oxide functions in interneuronal communication.

PMID- 7827347
TI  - Current therapeutic management of diabetic nephropathy.
AB  - Roughly 40% of all patients with insulin-dependent diabetes mellitus (IDDM)
      develop diabetic nephropathy with proteinuria, hypertension and a decrease in
      glomerular filtration rate 10 to 20 years after the onset of the disease, and 5
      years later most patients suffer from end-stage renal disease. Microalbuminuria,
      defined as an urinary albumin excretion rate (UAER) between 30 and 300 mg/day,
      strongly predicts the development of nephropathy in IDDM. Nearly all patients
      with IDDM, a decreasing glomerular filtration rate and a UAER > 300 mg/day have
      coexisting hypertensive disease additionally worsening renal function. We review
      the results of recent long-term studies of the current therapeutic management in
      diabetic patients by means of better blood pressure control, low-protein diet and
      near-normal blood glucose control in the early microalbuminuric phase as well as
      in the later phases of the disease characterized by diabetic nephropathy with a
      UAER > 300 mg/day. Since the large majority of studies have been performed on
      IDDM, our conclusions with regard to therapy are only valid in this subgroup of
      diabetic patients.

PMID- 7827348
TI  - Rigorous management of insulin-dependent diabetes mellitus during pregnancy.
AB  - The effect of rigorous management of insulin-dependent diabetes mellitus (IDDM)
      during pregnancy on the perinatal outcome was assessed by comparing 78 prepartum
      gravid patients with IDDM managed prospectively with 78 matched controls. The
      diabetic women were treated with insulin by either infusion pump or split-dose
      therapy, with the goal of normalization of the fasting blood sugars and
      hemoglobin Hb A1c values. Differences in the perinatal outcome were evaluated by
      either chi-square or analysis of variance. Of the women with IDDM, 14% where
      White class B, 43% class C, 26% class D, 17% classes R and F. The mean Hb A1c
      value in the first half of pregnancy was 8.49% +/- 2.30%, and 7.34% +/- 1.79% in
      the second half. Women with IDDM had higher rates of premature delivery (31% vs.
      10%, P = 0.003), pre-eclampsia (15% vs. 5%, P = 0.035), and cesarean section (55%
      vs. 27%, P = 0.002). Complications of infants born to diabetic mothers included
      large size for gestational age (41% vs. 16%, P = 0.0002), hypoglycemia (14% vs.
      1%, P = 0.0025), hyperbilirubinemia (46% vs. 23%, P = 0.0002), and respiratory
      distress (12% vs. 1%, P = 0.008). The Apgar scores and mortality were similar.
      Congenital malformations occurred in 7.7% of infants of diabetic mothers and 1.3%
      of controls (P = 0.05). The maternal Hb A1c level did not correlate with the
      infant size for gestation. Although the improved medical management of IDDM has
      decreased neonatal mortality, significant perinatal complications persist.

PMID- 7827349
TI  - Plasma beta-thromboglobulin and platelet factor 4 are not increased in insulin
      dependent diabetic patients with microalbuminuria.
AB  - To evaluate the possibility that platelet dysfunctions contribute to the
      cardiovascular risk of microalbuminuric insulin-dependent diabetic (IDD)
      patients, we have measured beta-thromboglobulin (BTG) and platelet factor 4 (PF4)
      in 74 IDD patients with different degrees of albuminuria (8 macro-, 36 micro- and
      30 normoalbuminuric) and in 30 non-diabetic control subjects. BTG values (20.4 +/
      1.5 SEM in normo-, 22.2 +/- 1.2 in micro-, 101.1 +/- 2.9 in macroalbuminuric
      patients and 21.8 +/- 1.1 IU/ml in control subjects) were significantly higher (P
      < 0.001) in the macroalbuminuric patients, but similar among the other groups.
      These results suggest that platelet hyperactivation is not present in the
      microalbuminuric stage of diabetic nephropathy, only in overt nephropathy.

PMID- 7827350
TI  - Impaired in vivo insulin secretion in response to non-glucidic secretagogues in
      adult rats after neonatal streptozotocin.
AB  - In the perfused pancreas of adult rats that were injected with streptozotocin
      (STZ) during the neonatal period, the release of insulin caused by glucose is
      more severely affected than that evoked by other secretagogues. We have now
      examined whether a comparable situation prevails in vivo. In anesthetised rats,
      the 0-10 min plasma insulin incremental area recorded after intravenous glucose
      administration (2.8 mumol/g body wt) was severely decreased in STZ rats, with a K
      value for glucose utilization of 1.9 +/- 0.2 x 10(-2)/min, as compared with
      control rats, with a K value of 4.4 +/- 0.4 x 10(-2)/min. At the 2nd min of the
      test, the plasma insulin increment was about 5 times lower in STZ than control
      rats. After glibenclamide administration (0.1 nmol/g body wt), the insulin
      incremental area was 3 times lower in STZ than control rats. Relative to the post
      prandial readings, the plasma glucose concentration was decreased to the same
      extent, however, in control and STZ rats injected with glibenclamide. The
      secretory response to succinic acid methyl ester (SAM; 1.0 mumol/g body wt) was
      virtually abolished in the STZ rats. In the latter animals, SAM also failed to
      enhance the hypoglycemic action of glibenclamide in contrast to the situation
      found in control rats. Iterative intraperitoneal administration of SAM (1.0
      mumol/g body wt) thrice daily for 7-10 days failed to improve significantly the
      insulin secretory response to glucose or glibenclamide, whether in control or STZ
      rats. These findings indicate that the altered metabolism of glucose in the B
      cell of STZ rats coincides with an impaired secretory response to glibenclamide
      and SAM, as possibly attributable, in part at least, to a loss of the modulating
      action of glucose upon the secretory response to the hypoglycemic sulfonylurea
      and succinate ester.

PMID- 7827351
TI  - Altered adrenal and thyroid function in children with insulin-dependent diabetes
      mellitus.
AB  - In 129 children, aged 12.6 +/- 3.8 years, affected by type 1 diabetes mellitus,
      the levels of dehydroepiandrosterone sulfate (DHEAS), cortisol, T3, fT3, T4, fT4,
      rT3, TSH, cholesterol, and triglycerides were evaluated and compared with those
      of a control group of 458 healthy age-matched children. The results were also
      correlated with hemoglobin HbA1C. The DHEAS-standard deviation score (DHEAS-SDS; 
      0.36 +/- 0.77) was significantly different from zero in diabetic children, while
      the cortisol serum level was higher than in control subjects (485 +/- 94 vs 359
      +/- 132 nmol/l). Moreover, the DHEAS-SDS and DHEAS-SDS/cortisol ratio correlated
      negatively with HbA1c. Diabetic patients also showed lower T3 values (2.22 +/-
      0.4 vs 2.32 +/- 0.3 nmol/l) and a higher rT3/T3 ratio (0.17 +/- 0.09 vs 0.15 +/-
      0.05) than controls. There was a negative correlation between T3 and HbA1C.
      Cholesterol (4.77 +/- 1.08 vs 4.51 +/- 0.76 mmol/l) and triglycerides (0.82 +/-
      0.53 vs 0.63 +/- 0.37 g/L) levels were higher in diabetic children and positively
      correlated with HbA1c, but not with DHEAS-SDS. We can therefore conclude that
      diabetes, particularly if poorly controlled, tends to induce a dissociation of
      cortisol and DHEAS secretion and a low T3 syndrome, similar to that seen in other
      illnesses.

PMID- 7827352
TI  - Embryonic growth impaired by maternal hypoglycemia during early organogenesis in
      normal and diabetic rats.
AB  - The effect of maternal hypoglycemia on early organogenesis was studied in normal
      and diabetic rats. Female Wistar rats were made diabetic by an intravenous
      injection of streptozotocin (45 mg/kg) 2-3 weeks before conception. On day 9.5 or
      10.5 of embryo development, both control and diabetic dams received saline or
      Actrapid human insulin (400 mU/rat) intraperitoneally after 19-h starvation. The
      fasting plasma glucose levels in diabetic dams decreased from approximately 23 to
      8 mM. Hypoglycemia as low as 3.5 mM was maintained for 60 min in insulin-treated
      mother rats. Pregnancy was terminated on day 11.6 of embryo development. A
      significant growth retardation was found in diabetic embryos as compared with
      normal embryos. Maternal hypoglycemia lowered the DNA content in normal but not
      diabetic embryos, while the teratogenic effect of maternal hypoglycemia was not
      pronounced in either normal or diabetic embryos. These data may suggest that
      maternal hypoglycemia in vivo in early pregnancy influences the embryogenesis but
      not teratogenesis of rat embryos.

PMID- 7827354
TI  - Effect of insulin and gliclazide on glucose utilization by a perfused intestine
      pancreas preparation isolated from diabetic and non-diabetic rats.
AB  - The effect of insulin (40 microU/ml) and gliclazide (200 micrograms/ml) on
      intestinal glucose metabolism was investigated by using an in vitro perfused
      intestine-pancreas preparation isolated from normal or streptozotocin-diabetic
      rats. Glucose, lactate and alanine were measured enzymatically in the portal
      effluent. The glucose retained by the perfused preparation was reduced (P < 0.05)
      in diabetic versus control rats. The portal lactate levels were not modified, but
      alanine portal levels were increased (P < 0.05) in diabetic versus control rats.
      In the diabetic rats, the level of glucose retained by the preparations was
      increased (P < 0.05) by the presence of insulin, and insulin plus gliclazide in
      the perfusate. In the presence of insulin and/or gliclazide, the portal lactate
      levels were not modified, but the alanine levels were reduced (P < 0.05) to
      normal values. In preparations from non-diabetic rats, the level of glucose
      retained was increased (P < 0.05) by gliclazide and insulin plus gliclazide,
      without modification of the portal lactate and alanine levels. In conclusion, the
      results show that both insulin and gliclazide increased glucose utilization by
      perfused intestine-pancreas preparations isolated from diabetic rats. The effect
      was enhanced when both substances were present simultaneously in the perfusion
      medium.

PMID- 7827353
TI  - Improved metabolic control does not reverse left ventricular filling
      abnormalities in newly diagnosed non-insulin-dependent diabetes patients.
AB  - In this study left ventricular diastolic function at rest was evaluated in ten
      newly diagnosed, non-insulin-dependent diabetic patients by Doppler
      echocardiography, performed at the onset of disease and after 6 and 12 months of
      adequate glycaemic control. Glycosylated haemoglobin A1C, total cholesterol and
      triglyceride levels were assessed at the same time. The control group consisted
      of ten healthy subjects of matching age and body mass index. The following
      parameters of left ventricular function were evaluated: ejection fraction (EF),
      peak velocity of the early (E) and late atrial (A) mitral flow, A/E ratio,
      duration of the early (Ei) and of the atrial (Ai) filling phase, and heart rate.
      The diabetic patients had significantly higher total cholesterol and triglyceride
      levels compared with healthy subjects. These remained elevated throughout the
      follow-up period, in spite of improved glycaemic control. A significantly shorter
      duration of Ei (0.15 +/- 0.008 vs 0.18 +/- 0.004, P < 0.01) and a higher value of
      A (0.51 +/- 0.02 vs 0.39 +/- 0.01, P < 0.001) and A/E (1.06 +/- 0.05 vs 0.73 +/-
      0.02, P < 0.001) were found in the diabetic patients before treatment. The
      parameters did not significantly change after 1 year of adequate glycaemic
      control. These results indicate a left ventricular filling abnormality which is
      present in newly diagnosed non-insulin-dependent diabetic patients and does not
      reverse with improved glycaemic control.

PMID- 7827355
TI  - Effect of sialic acid on glycation-induced fluorescence of albumin.
AB  - The aims of this study were to determine whether in vitro nonenzymatic glycation
      of proteins by sialic acid (sialylation) induces the generation of fluorescence,
      and whether the presence of this keto sugar may affect the generation of
      fluorescence induced by other sugars. Incubation of bovine serum albumin (BSA;
      1.5 mM) with sugars (50 mM in 0.2 M phosphate buffer, pH 7.4, at 37 degrees C)
      resulted in a time-dependent increase of formaldehyde release (moles/moles of
      protein). On the 17th day of incubation, the value was 0.53 +/- 0.06, 0.78 +/-
      0.15 and 1.23 +/- 0.18 for sialic acid, fructose and glucose respectively,
      compared with 0.37 +/- 0.05 for BSA. The fluorescence intensity (arbitrary
      units/mg protein) was higher after 17 days of incubation with fructose (16.9 +/-
      1.8) than with glucose (12.7 +/- 1.3), while no significant increase was noted
      with sialic acid compared with BSA (3.8 +/- 0.4). Fluorescence intensity increase
      by incubation with glucose (50 mM) was significantly reduced by sialic acid (20
      mM) after both 10 (P < 0.001) and 14 (P < 0.001) days of incubation, while
      inhibition was weaker after 14 (P < 0.05) than after 10 (P < 0.001) days when
      fructose (50 mM) was used as the glycating agent. This indicates that sialic acid
      can be potentially used to limit the damage from adverse glycation-induced
      processes.

PMID- 7827356
TI  - Enterostatin inhibits insulin secretion from isolated perifused rat islets.
AB  - The effect of enterostatin on glucose-induced insulin secretion was examined in
      isolated, perifused rat islets. In the presence of 16.67 mM glucose, there was
      significant inhibition of insulin secretion at concentrations of 200 nM, 2, 20
      and 40 microM enterostatin. In particular, the second phase of insulin secretion
      was inhibited. With a low concentration of glucose (2.78 mM), there was no
      significant effect on insulin secretion by enterostatin. The inhibition of
      insulin secretion exerted by enterostatin may be an important effect in the
      prevention of insulin resistance.

PMID- 7827357
TI  - Blood levels of insulin-like growth factors I and II in neonates of non-insulin
      dependent diabetic rats.
AB  - Circulating levels of insulin like growth factor I (IGF-I) and insulin like
      growth factor II (IGF-II) were evaluated in plasma samples during the first 72 h
      of life in neonates of diabetic and control mother rats. Diabetes had been
      induced in the diabetic dams by streptozotocin at 2 days of age. The rats
      developed non-insulin dependent diabetes (at 6 weeks of age) and became pregnant
      at 11 weeks of age. Maternal blood glucose levels were higher in the diabetic
      mothers (P < 0.05) during the last two-thirds of gestation. Complications
      occurred at the end of 7.1% of the diabetic pregnancies but none of the controls.
      Analysis of neonates plasma glucose, IGF-I, and IGF-II concentrations in the
      first 12, 24, 48, and 72 h after birth revealed higher glucose levels in neonates
      of diabetic mothers at 72 h compared with controls (118 +/- 7 vs 85 +/- 5 mg/dl,
      P < 0.05) but there was no difference in IGF-I or IGF-II levels between the
      groups at any time point. Thus, acquired impaired glucose homeostasis may be seen
      in neonates of mildly diabetic mothers at early stages of their life but their
      circulating insulin-like growth factors levels are normal. These data do not
      support the proposition that fetal IGF-I and -II affect the outcome of
      pregnancies complicated by mild diabetes in the rodent.

PMID- 7827358
TI  - Effects of non-esterified fatty acids on insulin-stimulated glucose transport in
      isolated skeletal muscle from patients with type 2 (non-insulin-dependent)
      diabetes mellitus.
AB  - The influence of elevated levels of oleate on insulin-stimulated 3-0
      methylglucose transport was assessed in vitro, in isolated skeletal muscle
      obtained from patients with type 2 (non-insulin-dependent) diabetes mellitus (n =
      7) and control subjects (n = 8). An increase in oleate levels from 0.3 to 1.0
      mmol/l induced a 3.7-fold increase in the rate of oleate oxidation (P < 0.01) in
      skeletal muscle from control subjects. However, the rate of insulin-stimulated 3
      0-methylglucose transport was not altered in isolated skeletal muscle from the
      control subjects or the type 2 diabetic patients following exposure to 1.0 mmol/l
      oleate. This observation indicates that elevation of non-esterified fatty acids
      to a high physiological level has no inhibitory effect on glucose transport.

PMID- 7827359
TI  - Disseminated intravascular coagulation and severe peripheral neuropathy
      complicating ketoacidosis in a newly diagnosed diabetic child.
AB  - Disseminated intravascular coagulation is a very rare complication of diabetic
      ketoacidosis. Central nervous system palsy but not peripheral neuropathy has been
      reported in these patients. On the other hand, signs of peripheral neuropathy may
      also be present at the onset of diabetes, but they are usually reversible within
      a few days after correction of the metabolic derangement. We describe an unusual
      case of mononeuritis multiplex syndrome still present after 2 months of follow-up
      in a child with diabetic ketoacidosis complicated by disseminated intravascular
      coagulation at the onset of insulin-dependent diabetes. These neurological
      impairments may be consistent with functional neural lesions due to vasa nervorum
      thrombosis and prolonged ischaemia.

PMID- 7827360
TI  - Characteristics of Enterococcus strains isolated in 1991-1992.
AB  - The paper presents the identification and resistance to antibiotics as well as
      the high-level resistance of 96 strains of enterococci isolated in 1991-1992 from
      patients admitted in the "Victor Babes" Hospital of Infectious Diseases. The
      identification of Enterococcus species using the Facklam-Collins schedule and
      several additional tests reveal 86.4% E. faecalis, 7.2% E. faecium, 4.1% E.
      gallinarum and 1.0% E. durans and 1% E. hirae. The high-level resistance to
      aminoglycosides was 69.8% for Streptomycin, 50%--Kanamycin and 21.8%--Gentamicin.
      The phenotype of resistance to Streptomycin, Kanamycin and Gentamicin was found
      in 19.8% of strains. 7.4% of enterococci had MIC values higher or equal to 32
      mcg/ml to Penicillin and MIC > or = to 16 mcg/ml to Ampicillin. Six E. faecalis
      strains and two E. gallinarum strains were resistant to Vancomycin.

PMID- 7827361
TI  - Experimental study upon the efficacy of some accelerated vaccination schedules in
      tetanus prophylaxis.
AB  - In an attempt to accelerate the antitetanic vaccine-induced immune response
      necessary particularly in subjects with tetanigenic wounds, groups of guinea pigs
      or rabbits were i.d. or s.c. immunized with a nonadsorbed purified and
      concentrated toxoid. Concomitantly, lots of control animals were i.m. immunized
      with tetanic vaccine adsorbed on aluminium phosphate. The immune response was
      estimated by testing the serum antitetanus antitoxic titre and the resistance of
      guinea pigs to tetanic intoxication. The results obtained revealed a variety of
      responses to vaccination in which differed terms of the species of animals and
      the applied immunization schedule. When single vaccine doses were used the
      protective antitetanus limit was reached in seven days in rabbits and after ten
      days in guinea pigs; the adsorbed vaccine induced a stronger immune response than
      the non-adsorbed vaccine. When multiple immunization doses were used the non
      adsorbed tetanus vaccine induced, especially in rabbits, a more rapid response
      that the adsorbed vaccine. The vaccination schedules used in laboratory animals
      and which have yielded the best results in this experiment will be analysed and
      checked on human subjects in a further study.

PMID- 7827362
TI  - DNA topology and V(D)J recombination: a tentative connection.
AB  - Gene recombination is the fundamental basis of immunoglobulin (Ig) and T cell
      receptor (TCR) diversity. Although several specific and nonspecific enzymatic
      equipments were revealed to be necessary for Ig and TcR gene assembly, almost
      nothing is known about the developmental and tissue specific control of
      recombination and the individual functions of the heptameric and nonameric
      signals and 12/23 spacers in this process. According to certain conformational
      and functional respects, we consider the nonamer a DNA insertion site to the
      nuclear scaffold, in relation with its structural homology to the satellite (5'
      ACAAACC-3') and microsatellite repetitions, involved in DNA-nucleoskeleton
      impact. A topological control for V(D)J recombination is proposed, through
      different accessibilities of the substrates in the catalytic site, defined by a
      specific nonamer-mediated insertion to the nuclear scaffold. Recognition of
      heptamer and nonamer sequences by RAG proteins is followed by the assembly of an
      asymmetric recombinant complex. Even more important in this assembly may be the
      role of nonamer which, through DNA flexibilization and bending, could participate
      at the formation of the enzyme core. This core with the attached DNA could have a
      nucleosome-like geometry, a motif present in certain DNA processing enzymatic
      systems. Such an assumption emerges from the close homology of the nonamers with
      the DNA mobilization intergenic sequences (CA5-6T), found in many eukaryotic
      organisms.

PMID- 7827363
TI  - Ultrastructural modifications in mice spleen after "Imunotim' treatment.
AB  - Imunotim, a polypeptidic extract from bovine thymus, induces the appearance of
      barrier cells in the spleen; these cells form a syncytial network and play an
      important role in blood cleaning. They are of fibroblastic origin. The cytoplasm
      of the cells in the network is dense and contains vesicles that seem to be
      detached from the nucleolemma. The nuclei are of small sizes. Cells (maybe
      lymphocytes) in different stages of disintegration can be seen in the network.

PMID- 7827364
TI  - Molecular aspects concerning antigen oligopeptide selection by MHC class I
      molecules.
AB  - T cells can recognize the antigen only if it is associated with self MHC
      molecules on the surface of antigen presenting cells (APC). There are several
      characteristic parameters defining interaction of MHC molecule with antigenic
      peptides giving circumstances for specific antigen presentation and an
      individualized immune response. Here are assessed some size and conformational
      parameters of the peptides presented by MHC class I molecules-lengths, widths,
      van der Waals volumes and surfaces-using COSMIC 2.0 software. The peptides
      derived from HIV gp 160 are obtained from literature and are known to be active
      and inactive in a cytotoxicity assay. An increased tendency for beta- or beta
      like structures and volumes close to those of the MHC binding site are
      encountered in the case of active peptides.

PMID- 7827365
TI  - Determination of serum myoglobin by the reverse passive hemagglutination assay
      (RPHA) and radioimmunoassay (RIA).
AB  - Serum myoglobin (Mb) is an important biological marker in the early diagnosis of
      the acute myocardial infarction (AMI). In a previous paper we showed that RPHA,
      which consists in the agglutination of anti-Mb antibody--coated erythrocytes by
      solutions containing Mb, is a simple, rapid and highly sensitive assay (approx. 1
      ng/ml). 42 sera from AMI patients and 20 sera from healthy subjects were
      investigated by RPHA. The geometric mean (x/divided by SD) of serum Mb titers in
      AMI patients was 362 x/divided by 3.94, in the range of 64-8192 (the reciprocal
      dilutions) and in normal sera was 19 x/divided by 1.36, in the range of 16-32.
      The difference between the mean values was statistically significant at p <
      0.001. Subsequently, serum Mb concentration was determined by RPHA and RIA in 51
      AMI sera prelevated at various stages of the disease. A high degree of
      correlation was found between the two methods. Log Y (RPHA titers) = -0.9174 +
      1.5879 log X (RIA); ESE: +/- 0.1947; r = 0.9601. In four AMI patients successive
      determinations were made at every 6 hours: serum Mb curves determined by RPHA and
      RIA had a parallel evolution and this was an additional argument for the
      validation of RPHA. Being quite simple and easy of execution RPHA is the most
      suitable method by which an early AMI diagnosis can be made.

PMID- 7827366
TI  - Role of complement inhibition in topical therapy of muco-cutaneous herpes simplex
      virus infections.
AB  - A complement-inhibiting formulation with anti-inflammatory activity due to
      suppression of both the classical and alternative pathways of complement
      activation is presented for local treatment of muco-cutaneous lesions produced by
      Herpes simplex virus, types 1 and 2. The drug contains glutaraldehyde, a strong
      inhibitor of the complement system, dimethylsulphoxyde, used as a vector
      modifying the barrier properties of the skin and 1,2-propylene glycol, a
      delipidating agent which increases the adhesiveness of the watery solutions to
      the skin surface. It proved to be devoid of adverse effects for normal skin of
      animal and humans, and produced rapid disappearance of herpetic neuralgia and
      accelerates the remission of local symptoms. The mechanism of action seems to be
      associated with the inhibition of local anaphylatoxin release (C3a and C5a) which
      are responsible for the acute evolution of the lesions produced by viruses of the
      Zoster-Varicella group and with a quick lethal effect on the parasitized cells
      which are selectively eliminated without affecting the adjoining normal cells of
      the host.

PMID- 7827367
TI  - Health care delivery for chronic congestive heart failure in the United Kingdom.
AB  - Since the United Kingdom has fewer cardiology specialists than other countries,
      the United Kingdom cardiologist cannot provide direct care for all patients with
      chronic congestive heart failure (CHF). Most CHF care is provided by general
      practitioners, physicians or geriatricians. A survey of 100 CHF patients
      attending a health center revealed that these patients visited their general
      practitioners 270 times in 1 year, compared with only 34 outpatient visits. The
      cardiologist mainly provides echocardiography. The accurate diagnosis of mild CHF
      became imperative with the advent of angiotensin converting enzyme (ACE)
      inhibitors. Results of a survey showed that although 1.6% of the population are
      taking diuretics for CHF, only 0.84% of the population have left ventricular
      systolic dysfunction on echocardiography. An estimated 22 echocardiograms per
      1000 population per year are required (10 for structural reasons, three for
      suspected new CHF, three to identify patients with a low left ventricular
      ejection fraction and six to identify left ventricular hypertrophy in
      hypertensive patients). However, district general hospitals in Scotland can only
      provide 3.3-6 echocardiograms per 1000 population per year. The elderly CHF
      patient may not receive adequate treatment because of the lack of resources and a
      dislike of 'overinvestigating' or 'overtreating' the elderly. The benefits of
      echocardiography and ACE inhibitor therapy for all patients with CHF should be
      stressed.

PMID- 7827368
TI  - Heart failure resolved? An interactive debate. Practical challenges.
AB  - Case histories for three patients with heart failure were presented to an
      audience of cardiologists, general physicians, geriatricians and other
      specialists. The delegates responded via key pads to questions concerning
      management of the patients. The value of noninvasive investigations (eg, chest X
      ray, electrocardiogram, echocardiogram, exercise test) in establishing the
      diagnosis, management and prognosis was demonstrated. Most delegates indicated
      that they would prescribe angiotensin converting enzyme (ACE) inhibitors in mild
      to moderate heart failure, although low doses were preferred to high doses in
      elderly patients. The importance of avoiding nonsteroidal anti-inflammatory drugs
      in patients on ACE inhibitor therapy was illustrated.

PMID- 7827369
TI  - The cardiac structure-function relationship and the renin-angiotensin-aldosterone
      system in hypertension and heart failure.
AB  - According to the Framingham Study, arterial hypertension and coronary artery
      disease are the major etiologic factors in the development of heart failure.
      Regulatory systems that may affect heart failure include the Frank-Starling
      mechanism, neurohormonal responses, cardiac growth and peripheral oxygen
      delivery. Recently, the interrelationship between the neuroendocrine system and
      cardiac growth has aroused much interest. In the pressure- or volume-overloaded
      heart, hypertrophic growth of the myocardium includes the enlargement of cardiac
      myocytes, an adaptation governed by ventricular loading. Nonmyocyte cell growth
      involving cardiac fibroblasts may also occur but is not primarily regulated by
      the hemodynamic load. Cardiac fibroblast activation is responsible for the
      accumulation of fibrillar type I and type III collagens within the interstitium
      and adventitia of intramyocardial coronary arteries, while vascular smooth muscle
      cell growth accounts for the medial thickening of these vessels. This remodeling
      of the cardiac interstitium is a major determinant of pathological hypertrophy in
      that it accounts for abnormal myocardial stiffness and impaired coronary
      vasodilator reserve, leading to ventricular diastolic and systolic dysfunction
      and, ultimately, symptomatic heart failure. Several lines of evidence suggest
      that the renin-angiotensin-aldosterone system is involved in regulating the
      structural remodeling of the nonmyocyte compartment; this accounts for the
      cardioprotective effects of angiotensin converting enzyme (ACE) inhibition, which
      prevents myocardial fibrosis in rats with renovascular hypertension. In rats with
      genetic hypertension, established left ventricular hypertrophy, abnormal
      diastolic stiffness due to interstitial fibrosis and reduced coronary vasodilator
      reserve associated with medial wall thickening of intramyocardial resistance
      vessels, the ACE inhibitor lisinopril restored myocardial structure and function
      towards normal.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7827370
TI  - Optimizing the treatment of heart failure.
AB  - The introduction of new drugs, and a re-evaluation of older drugs, have radically
      changed the pharmacological management of heart failure. Angiotensin converting
      enzyme (ACE) inhibitors, digitalis, diuretics and the combination of nitrates and
      hydralazine are now used. The first Cooperative North Scandinavian Enalapril
      Survival Study (CONSENSUS I) and the second Vasodilator therapy in Heart Failure
      Trial (V-HeFT II) have demonstrated that patients with severe or advanced heart
      failure should be treated with ACE inhibitors, digitalis and diuretics (other
      vasodilators can be used if ACE inhibitors are contraindicated) to improve
      symptoms and duration of life. The Studies Of Left Ventricular Dysfunction
      (SOLVD) and the Munich Heart Failure trial have shown that patients with mild
      heart failure should be treated with ACE inhibitors. However, data from several
      large clinical registries suggest that only 40% of patients with heart failure
      are being given ACE inhibitors perhaps through fear of serious renal damage or
      hypotension; these fears are unfounded. Patients with anterior myocardial
      infarcts and reduced left ventricular function also benefit from ACE inhibitors.
      The fourth International Study of Infarct Survival (ISIS 4) and results from the
      Gruppo Italiano per Io Studio della Sopravvivenza nell'Infarto miocardico 3
      (GISSI 3) have indicated that patients with acute myocardial infarction benefit
      from early ACE inhibitor therapy and that survival is increased. Heart failure
      treatment can be optimized by establishing a disease etiology and stressing the
      need to restrict dietary sodium. ACE inhibitors should be used for depressed left
      systolic ventricular function, including patients in New York Heart Association
      class I heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7827371
TI  - Endothelin and collagen vascular disease: a review with special reference to
      Raynaud's phenomenon and systemic sclerosis.
AB  - Endothelin-1 (ET-1), endothelin-2, and endothelin-3, a family of 21-aminoacid
      peptides, are potent, long-acting vasoconstrictors of mammalian blood vessels.
      Elevated levels of ET-1 have been found in the circulation of patients with
      various diseases, all of which have some degree of vascular involvement that is
      associated with endothelial cell activation. These diseases include systemic
      sclerosis, primary and secondary Raynaud's phenomenon, pulmonary hypertension,
      Buerger's disease, and Takayasu's arteritis. The role of circulating ET-1 in the
      pathogenesis of the vascular and fibrotic lesions in these conditions remains to
      be elucidated. This review focuses on the recent findings of the clinical
      significance and pathogenetic role of endothelin in collagen vascular diseases,
      especially in Raynaud's phenomenon and systemic sclerosis. Although the etiology
      of systemic sclerosis is unknown, a vascular pathogenesis is supported by a
      variety of clinical and laboratory observations. The fact that plasma levels of
      ET-1 are elevated in patients with systemic sclerosis and this elevation is more
      remarkable in patients with diffuse scleroderma compared with limited scleroderma
      patients might further support the vascular pathogenesis of systemic sclerosis.

PMID- 7827372
TI  - Elevated serum interleukin-6 in POEMS syndrome reflects the activity of the
      disease.
AB  - In patients with POEMS syndrome, which often accompanies plasma cell dyscrasia,
      the roles of interleukin-6 (IL-6) and other acute phase cytokines are unknown.
      Serum IL-6, interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF
      alpha) were measured by the enzyme-linked immunosorbent assay technique in 16
      patients with POEMS syndrome and in patients with other neurological diseases
      (OND) as control. Serum IL-6 was more frequently detected and higher in active
      POEMS than in stable POEMS or in OND patients. No sample was positive for IL-1
      beta. TNF-alpha was positive in 3 out of 7 active POEMS patients, but its
      significance was not definite. Serum IL-6 levels in POEMS patients reflected the
      disease activity but not the severity of accompanying plasma cell dyscrasia.

PMID- 7827373
TI  - Octreotide decreases biliary and pancreatic exocrine function, and induces
      steatorrhea in healthy subjects.
AB  - A somatostatin analogue (SMS-201-995, hereinafter "octreotide") was s.c.
      administered to 5 healthy subjects under consecutive dripping of CCK-PZ
      (cholecystokinin-pancreozymin) and secretin (0.01 CHR U/kg/minutes), after
      inserting a Dreiling double tube into Treitz's ligament. Bile acid concentration,
      and bicarbonate and lipase excretions in duodenal juice were determined every 10
      minutes up to 120 minutes and compared with controls. Moreover, octreotide (100
      micrograms) was s.c. administered to 5 healthy subjects 30 minutes before meals
      for 7 days. Fecal fat and bile acid excretions before and after administration
      were determined. Bile acid concentration, and bicarbonate and lipase excretions
      in the octreotide group decreased to 1/3-1/4 that of controls. Bile acid
      concentration became 0 mM for 60 minutes. Fecal fat excretion increased; obvious
      steatorrhea occurred in 2 cases. Fecal bile acid excretion decreased to about
      1/4. These results suggest that decreases in bile acid secretion should be
      considered, as well as pancreatic lipase and bicarbonate secretions, when fatty
      stool occurs after octreotide administration.

PMID- 7827374
TI  - Endoscopic endoprosthesis for large stones in the common bile duct.
AB  - Endoscopic biliary endoprosthesis was performed for 34 high-risk patients with
      common bile duct stones too large to be extracted by conventional endoscopic
      means. Bile duct drainage was established in all the patients without
      complications. Late complications developed in four patients and included
      cholangitis (three) and biliary pain (one). Twenty-five patients underwent a
      second endoscopic retrograde cholangiopancreatography between 4 and 30 months
      (mean, 15.1) during follow-up. Stone fragmentation was obtained in 76% (19/25) of
      the patients. Ten patients had complete stone clearance, and nine patients had
      disintegrated stones which could be readily removed endoscopically. The remaining
      nine patients were followed up with endoprostheses in situ for four to 60 months
      (mean, 24.8) without any symptoms. These results suggest that endoscopic
      endoprosthesis for difficult common bile duct stones is an effective method to
      clear the duct in selected cases, as well as an important definitive treatment in
      high-risk patients.

PMID- 7827375
TI  - Addison's disease in Japan: characteristics and changes revealed in a nationwide
      survey.
AB  - Patients with Addison's disease, newly diagnosed in the last five years were
      surveyed nationwide in conjunction with two past surveys. The decreasing
      incidence, i.e., 168 patients from 1977 to 1981 (survey 1), 108 from 1982 to 1986
      (survey 2), and 74 from 1987 to 1991 (the present survey), reflects a decrease in
      the incidence (n = 28) of tuberculous Addison's disease, but not that (n = 36) of
      idiopathic Addison's, making the idiopathic form predominant for the first time
      in the history of the disease in Japan. Because the interval between the
      preceding tuberculosis and the onset of Addison's averages 32 +/- 15 years,
      tuberculous Addison's has a relatively late onset. Pigmentation is the most
      frequent symptom (90%). Other symptoms, abnormal laboratory data, and positive
      adrenal antibodies are observed less frequently in Japan than in North America or
      Europe. The types of associated disorders are also distributed differently.
      Adrenal CT and MRI scans have been the most useful means in differentiating
      between the two major types of the disease. This report focuses on features
      distinguishing Japanese sufferers from their western counterparts.

PMID- 7827376
TI  - Hemophagocytic syndrome in a patient with rheumatoid arthritis.
AB  - A 63-year-old female, who had been diagnosed with rheumatoid arthritis (RA) 3
      years previously, was admitted due to progressive pancytopenia, lymphadenopathy,
      fever, and weight loss. The physical and laboratory findings fulfilled all of the
      American Rheumatism Association (ARA) revised criteria for RA. Her bone marrow
      aspirate revealed a decreased nuclear cell count (1.8 x 10(4) microliters) and
      megakarocyte count (0/microliter), and macrophages phagocytizing blood cells
      (4%), indicating the presence of hemophagocytic syndrome. The serological tests
      for several viruses revealed no obvious viral etiology. However, a slight Epstein
      Barr virus (EBV) reactivation could not be excluded. Administration of 40 mg
      prednisolone daily improved her abnormal hematological findings and immunological
      laboratory parameters. This is a case of RA accompanied by hemophagocytic
      syndrome, which has not been reported previously as a complication of RA.

PMID- 7827377
TI  - Diffuse panbronchiolitis and rheumatoid arthritis: a possible correlation with
      HLA-B54.
AB  - We analyzed the HLA antigens in two patients with rheumatoid arthritis
      accompanied by diffuse panbronchiolitis in whom HLA typing could be done and
      found the presence of B54 and DR4 alleles. We previously reported that the
      frequency of HLA-B54 is significantly increased in patients with diffuse
      panbronchiolitis. This allele demonstrates a linkage disequilibrium with DR4 (or
      DR4.1) in Japanese individuals. The association of rheumatoid arthritis with HLA
      DR4 is well established in various ethnic groups including Japanese people. Since
      both diseases show the same pattern of HLA correlation, more Japanese patients
      with these two diseases are likely to be encountered.

PMID- 7827378
TI  - Recovery from rheumatoid cerebral vasculitis by low-dose methotrexate.
AB  - We report the successful management of cerebral vasculitis in a 46-year-old woman
      with longstanding rheumatoid arthritis with low-dose methotrexate. She suddenly
      developed dysarthria and left hemiparesis. Magnetic resonance imaging disclosed
      ischemia of the right pons, and angiography demonstrated cerebral vasculitis of
      vertebro-basilar arteries. The vasculitis was refractory with high-dose steroid
      therapy, which had only transient clinical benefit, and evolution to the pontine
      infarction followed. Her clinical status showed marked improvement in association
      with recovery of the vascular abnormalities after the initiation of the
      methotrexate therapy.

PMID- 7827379
TI  - Schwannoma of the duodenum causing melena.
AB  - A rare case of duodenal schwannoma is reported. A 69-year-old man was admitted
      for evaluation of melena. Endoscopy and hypotonic duodenography showed a
      submucosal tumor in the third part of the duodenum. Biopsy findings were
      suggestive of leiomyosarcoma, therefore pancreatoduodenectomy was performed.
      Hematoxylin-eosin staining of the resected specimen showed interlacing bundles of
      spindle-shaped cells with palisading nuclei. Immunohistochemical staining showed
      positivity for S-100 protein and neuron-specific enolase, but desmin was
      negative, thus a diagnosis of schwannoma was made. Schwannoma is often difficult
      to distinguish from leiomyogenic tumors by standard staining, but
      immunohistochemical staining proved useful in this case.

PMID- 7827380
TI  - Malignant pleural mesothelioma presenting as achalasia.
AB  - A 65-year-old man with an occupational history of asbestos exposure developed
      dysphagia and vomiting. Clinical examinations at onset revealed a dilated
      esophagus with smooth narrowing at the gastroesophageal junction and no apparent
      tumor in and around the esophagus. Achalasia was suspected. Dysphagia progressed
      gradually and examinations performed three months after the onset disclosed a
      tumor in the pleural and the peritoneal cavities. At laparotomy, the tumor
      extended from the pleural cavity into the peritoneal cavity. Histological
      examination of the biopsied specimen demonstrated malignant mesothelioma. We
      report the first case of malignant pleural mesothelioma presenting as achalasia.

PMID- 7827381
TI  - Infective endocarditis caused by an indigenous bacterium (Gemella morbillorum).
AB  - A case of infective endocarditis (IE) caused by a rare pathogen, Gemella
      morbillorum, is presented. Because of persistent low-grade fever after dental
      treatment, the patient was given oral antibiotics. Whereas he was diagnosed as
      having aortic regurgitation by a cardiologist, and IE was not suggested
      unfortunately. After long-term chemotherapy over five months, he was aware of
      nocturnal dyspnea and Gemella morbillorum was detected by blood culture. Then, he
      was treated with intravenous administration of Penicillin-G, and underwent
      surgical operation for valve replacement. No cases of IE due to this organism
      have been reported in Japan.

PMID- 7827382
TI  - Severe insulin-resistant diabetes mellitus associated with hypereosinophilic
      syndrome.
AB  - We describe a 52-year-old male manifesting severe insulin resistance associated
      with hypereosinophilic syndrome (HES). Diabetes mellitus was initially well
      controlled by an oral hypoglycemic agent, and thereafter by human insulin. Due to
      the progression of hypereosinophilia, hepatosplenomegaly and peripheral
      lymphoadenopathy, severe insulin resistance associated with diabetic ketoacidosis
      occurred repeatedly, despite intravenous administration of over 1,000 U per day
      of human insulin. A high plasma insulin-binding capacity as determined by
      Scatchard analysis was consistent with insulin antibody-mediated resistance. The
      diagnosis of HES was made due to the persistent elevation of eosinophil count and
      associated liver and cardiac damage. Glucocorticoid therapy successfully achieved
      both reducing clinical symptoms and improving glycemic control.

PMID- 7827383
TI  - Abducent nerve paralysis during interferon alpha-2a therapy in a case of chronic
      active hepatitis C.
AB  - A 59-year-old woman with chronic active hepatitis C was treated with recombinant
      human interferon alpha-2a. After three days of administration, the patient
      complained of diplopia with dizziness and head heaviness. Ophthalmic examinations
      revealed a disturbance of the movement of left eye ball to the outer side without
      any other neurological signs. The diplopia, which was diagnosed as abducent nerve
      paralysis, improved rapidly and reversed at about 6 weeks after discontinuation
      of interferon and during infusion of hydrocortisone. To our knowledge, this is
      the first report of abducent nerve paralysis associated with alpha-2a interferon.

PMID- 7827384
TI  - Pigmentary retinopathy with nephrotic syndrome, Menetrier's disease, and diabetes
      mellitus.
AB  - A patient with pigmentary retinopathy, nephrotic syndrome, Menetrier's disease,
      and diabetes mellitus is presented. Other complications were congestive heart
      failure, hypothyroidism, hypertension, and hypertriglyceridemia. Hypogenitalism
      was also suspected. Pigmentary retinopathy is known to associate with many
      systemic diseases, which are classified into several syndromes. This case
      superficially resembles Alstrom's disease due to the common characteristics of
      pigmentary retinopathy, diabetes mellitus, renal disease, and hypogenitalism. But
      clinically and histologically, there are distinct differences. To our knowledge,
      this association has never been reported.

PMID- 7827385
TI  - A rare case of Young's syndrome in Japan.
AB  - A 56-year-old man was admitted for the evaluation of recurrent pulmonary
      infections. Since the patient presented with the combination of diffuse cystic
      bronchiectasis, chronic sinusitis and obstructive azoospermia, the diagnosis of
      Young's syndrome was made. Because the sweat chloride value, pancreatic function
      and ciliary ultrastructure were normal, this case could be clearly differentiated
      from cystic fibrosis and primary ciliary dyskinesia. There have been only a few
      reported cases of Young's syndrome in Japan.

PMID- 7827386
TI  - Successful continuous treatment with all-trans retinoic acid for acute
      promyelocytic leukemia; secondary malignancy after the treatment of osteosarcoma.
AB  - We report a rare case of complete remission for 32 months with continuous
      treatment with all-trans retinoic acid (ATRA) alone in a patient with acute
      promyelocytic leukemia which developed as a second malignancy after the treatment
      of osteosarcoma after failure of conventional chemotherapy. The adverse effects
      of ATRA were apparently tolerable.

PMID- 7827387
TI  - The trouble with 'quality'.
AB  - Much like that elusive but sought-after commodity, beauty, quality lies to a
      great extent in the eye and mind of its beholder. Whilst some are content with
      second-hand goods, others insist that only the best will do, the judgement of
      what is the best being a very individual phenomenon. The mechanical aspects of
      quality are those things which are visible or tactile: cleanliness, completeness,
      adequate numbers, smiling faces, quickly answered phones. All of these may be
      visible and present in a unit which offers a poor quality service. Behind the
      smiling faces, the efficiently answered phone, may lie a philosophy of total self
      centredness, a value system based on clock watching and working strictly within a
      job description. This person may never give that important small sacrifice which
      puts another's needs ahead of their own.

PMID- 7827388
TI  - Planning operating departments. Who does it?

PMID- 7827389
TI  - MARU.
AB  - MARU is a research, postgraduate teaching, information and consultancy unit based
      in the School of Architecture and Interior Design at the University of North
      London. We are particularly concerned with the match between health care services
      and facilities. Our role is to keep abreast of changing philosophies in health
      service provision and develop ideas and strategies for creating the built
      environment to implement these changes. We undertake research and consultancy on
      commission with current specific areas of activity in developing databases of
      past research in the field, design guidance for primary care buildings for LIG
      and the Department of Health, strategic studies of services, organisation and
      space use at primary, secondary and tertiary levels of care.

PMID- 7827390
TI  - Adopting strategies to reduce healthcare litigation and complaints.
AB  - Patients are bringing more court actions and are making more formal complaints
      then ever before. The reasons are various and range from the Patient's Charter
      making patients more informed to the publicity of successful court cases and
      complaints alerting patients to their right to sue and complain. Whatever the
      reason for bringing the claim or making the complaint it is important for
      healthcare to reflect on the reasons for the increase and to adopt strategies for
      reduction. Litigation and complaints cost health authorities and patients
      valuable time and money. Going to court and mounting a formal complaint can also
      be an emotionally stressful experience for all those involved.

PMID- 7827391
TI  - Adult intubation for beginners.
AB  - The UKCC's 'Scope of Professional Practice' validly points out that, 'Practice
      takes place in a context of continuing change and development' partly 'as a
      result of new approaches to professional practice'. Consequently, demands are
      made on educational institutions to prepare professionals for new practice. One
      of the new skills, which is now being taught to nurses on the Anaesthetic Nursing
      Course at the Eastern Area College, is that of endotracheal intubation. Bearing
      in mind the all-important proviso that 'As a registered nurse, midwife or health
      visitor, you are personally accountable for your practice', it is essential that
      post registration education 'equips practitioners with additional and more
      specialist skills necessary to meet the special needs of patients and clients'.
      This article is therefore designed as an introduction to the basic rationale,
      anatomy and procedural skills necessary for safe intubation.

PMID- 7827392
TI  - Theatre nursing (2).
AB  - Lyn Holmes continues her account of how she explored the topic of nursing care in
      her operating department. She goes on to describe the questionnaire she devised
      to test theatre nurses attitudes to and knowledge of primary nursing.

PMID- 7827393
TI  - NVQ theatre training.

PMID- 7827394
TI  - Psychotropic drugs, aging and community care.

PMID- 7827395
TI  - Vaccinating elderly people. Protecting from avoidable disease.
AB  - A large portion of our older adult patients remain unimmunised or inadequately
      immunised against tetanus. The US is unique in that clinical tetanus occurs
      mostly in persons aged over 60 years. Worldwide, it is a disease of neonates.
      Both pneumococcal diseases and influenza cause markedly greater morbidity and
      mortality among elderly people compared with younger people. The prevalence of
      these chronic diseases can be decreased by immunising susceptible persons against
      the relevant infections. Hepatitis B is also a worldwide problem, causing a large
      number of acute infections and costly sequelae, 95% of which is preventable by
      hepatitis B vaccine. Rabies is a very lethal disease preventable by use of rabies
      vaccine. The decreased function of the aging immune system results in far fewer
      older persons developing antibodies following immunisation than their younger
      counterparts.

PMID- 7827396
TI  - Pharmacological management of schizophrenia in older patients.
AB  - Although antipsychotic drugs are the mainstay of treatment in older patients with
      schizophrenia, much of the theoretical work underpinning their use is based on
      evidence gained from younger patients. With respect to dosages, there has been
      little work comparing plasma concentrations of antipsychotics in older patients
      with those of younger patients. However, there are well documented changes in the
      pharmacokinetics of these drugs in the elderly, particularly in their hepatic
      metabolism and renal excretion. There is also evidence that older patients
      experience more adverse effects from antipsychotics than younger patients. Such
      effects include extrapyramidal symptoms, postural hypotension and falls. For
      these reasons it is recommended that starting doses of antipsychotic drugs in
      older patients should be in the region of 25 to 50% of that recommended for
      younger patients, and should be slowly increased. Selection of a particular
      antipsychotic agent is best made on the basis of individual patient
      characteristics and the adverse effect profiles of particular drugs.

PMID- 7827398
TI  - Epidemiology of stroke. Importance of preventive pharmacological strategies in
      elderly patients and associated costs.
AB  - Stroke is a major cause of death and disability in developed countries. The
      incidence of stroke increases exponentially with age, yet, traditionally, many
      medical practitioners have been reluctant to treat hypertension in older
      patients. Since 1991, the results of 3 major trials--the British Medical Research
      Council (MRC) trial of treatment in older adults, the Swedish Trial in Old
      Patients with Hypertension (STOP-Hypertension) and the Systolic Hypertension in
      the Elderly Program (SHEP)--have conclusively established the benefits of
      treating older patients (> 60 years) with both diastolic and isolated systolic
      hypertension. International guidelines for the management of hypertension-
      including the Fifth Report of the Joint National Committee, the 1993 report of
      the World Health Organization and the International Society of Hypertension and
      the second report of the British Hypertension Society Working Party--have all
      been modified to reflect the emerging evidence concerning the benefits of
      treating older patients. Cost-effectiveness data are similarly in accord with
      giving high priority to the treatment of older individuals with hypertension.

PMID- 7827397
TI  - Do calcium channel blockers have renal protective effects?
AB  - Calcium channel blockers are used in the treatment of hypertension because of
      their ability to decrease peripheral vascular resistance. Recent research has
      suggested that these drugs also preserve or improve renal function in patients
      with essential hypertensive renal disease or diabetic renal disease, and in renal
      transplant recipients with or without cyclosporin therapy. In general, studies in
      animal models of hypertension and in hypertensive humans have demonstrated
      reduction in renal vascular resistance, and preservation or enhancement of renal
      plasma flow and glomerular filtration rate. In addition, calcium channel blockers
      appear to have a positive effect on renal addition, calcium channel blockers
      appear to have a positive effect on renal haemodynamic function in the setting of
      diabetes mellitus; prospective trials have also demonstrated reductions in
      urinary protein excretion in these patients. Current evidence suggests that
      calcium channel blockers are well-suited for the treatment of patients with
      hypertensive disease even in the presence of renal impairment, a clinical
      scenario common in the elderly population.

PMID- 7827399
TI  - Calcitriol. A review of its use in the treatment of postmenopausal osteoporosis
      and its potential in corticosteroid-induced osteoporosis.
AB  - A synthetic form of calcitriol (1,25-dihydroxycholecalciferol; 1,25
      dihydroxyvitamin D3), the most physiologically active metabolite of vitamin D,
      has shown efficacy in the treatment of postmenopausal osteoporosis and promise in
      corticosteroid-induced osteoporosis. Although results of small studies
      investigating calcitriol in the treatment of postmenopausal osteoporosis have
      been conflicting, a clinical trial in 622 women with postmenopausal osteoporosis
      demonstrated that patients with mild to moderate disease who received calcitriol
      (0.25 microgram twice daily) had a significant 3-fold lower rate of new vertebral
      fractures after 3 years of treatment, compared with patients receiving elemental
      calcium 1000 mg/day. In patients commencing long term treatment with prednisone
      or prednisolone, calcitriol 0.5 to 1.0 micrograms/day plus calcium 1000 mg/day,
      administered with or without intranasal calcitonin 400 IU/day, prevented steroid
      induced bone loss. Overall, calcitriol is well tolerated. As shown in clinical
      studies, at recommended dosages hypercalcaemia is infrequent and mild, generally
      responding to reductions in calcium intake and/or calcitriol dosage. The narrow
      'therapeutic window' of calcitriol requires that its use be adequately
      supervised, with periodic monitoring of serum calcium and creatinine levels.
      However, significant renal toxicity has not been seen in patients with
      osteoporosis treated with calcitriol in high dosages for several years in
      comparative and noncomparative trials. In conclusion, as with other drugs
      currently used in the management of patients with osteoporosis, questions remain
      to be answered regarding the efficacy of calcitriol relative to other agents, and
      its tolerability in such patients during the very long term. Nonetheless, at this
      stage, calcitriol should be considered a useful treatment option in patients with
      mild to moderate postmenopausal osteoporosis.

PMID- 7827400
TI  - Lectins in AIDS research.

PMID- 7827401
TI  - Capillary electrophoresis of carbohydrates.
AB  - Capillary electrophoresis has emerged as a highly promising technique for the
      analysis of mono- and oligosaccharides. The approaches developed for overcoming
      the lack of chromophoric and fluorophoric functions in most carbohydrates involve
      the use of indirect photometric detection, amperometry, mass spectrometry, and
      precolumn derivatization with various tags. The merits and drawbacks of the
      derivatizing agents, including 2-aminopyridine, 4-amino-benzoic acid and its
      analogues, which for the first time permitted the reproducible determination of
      aldoses, uronic acids and even ketoses in the low femtomole range by means of
      readily available UV detection, and other agents such as 8-aminonaphthalene-1,3,6
      trisulphonic acid, 1-phenyl-3-methyl-5-pyrazolone and 3-(4-carboxybenzoyl)-2
      quinoline-carboxaldehyde, are discussed in detail. Means to secure
      electromigration of the usually neutral carbohydrates are: (i) ionization of
      hydroxyl groups at high pH; (ii) complexation of vicinal or alternate hydroxyl
      groups with borate or other charged compounds such as alkaline earth metal ions;
      (iii) derivatization with a reagent possessing ionizable functions; and (iv)
      partitioning into a pseudostationary phase such as sodium dodecyl sulphate
      micelles. Each alternative has its own analytical rewards, and combinations of
      the above mechanisms allow the two-dimensional and perhaps even three-dimensional
      mapping of oligosaccharides. Pyridylaminated oligosaccharides, for instance, have
      been separated both according to size by exploiting differences in the charge-to
      mass ratio, with the charge being identical for each oligomer under acidic
      conditions due to protonation of the imino group incorporated by precolumn
      derivatization, as well as on the basis of structural differences, as a
      consequence of differences in the ease of borate complexation of the peripheral
      monosaccharide residues. It is also shown that the 4-aminobenzonitrile
      derivatives of mono- and disaccharides can be separated by micellar
      electrokinetic chromatography with a resolving power superior to that achieved by
      capillary zone electrophoresis of sugar-borate complexes. Based on the progress
      made, it can be concluded that capillary electrophoresis represents a powerful
      alternative and complement to existing methodology in the area of carbohydrate
      analysis.

PMID- 7827402
TI  - Towards characterizing O-glycans: the relative merits of in vivo and in vitro
      approaches in seeking peptide motifs specifying O-glycosylation sites.

PMID- 7827403
TI  - Wild-type and cultured Ehrlich ascites tumour cells differ in tumorigenicity,
      lectin binding patterns and binding to basement membranes.
AB  - Three different variants of the Ehrlich ascites tumour (EAT) cell were derived
      and the lectin surface reactivities, as well as the malignant characteristics of
      each variant, were studied. Wild-type cells (EAT-wt) were selected for growth on
      basement membranes and tissue culture plastic to give EAT-c cells. The EAT-c were
      passaged in mice by i.p. injection, giving rise to a third variant (EAT-c/m).
      Each of these three cell variants was characterized for: (i) specific lectin
      agglutinability patterns; (ii) the ability to produce ascites tumours in mice;
      (iii) the ability to produce solid tumours; and (iv) the attachment to and growth
      on basement membranes and purified extracellular matrix molecules. Analysis of
      the total protein and carbohydrate content of each cell line showed that there
      was an increase in the glycosylation of the EAT-c cells compared to EAT-wt cells.
      After repeated passage of the EAT-c/m cells in mice, the glycosylation level of
      the EAT-c/m cells returned to that of the EAT-wt cell line. In addition, the EAT
      c cells displayed an increase in the number of terminal non-reducing sugars which
      could indicate either an increase degree of branching or the presence of
      additional N- and/or O-linked oligosaccharide chains of the cellular
      glycoproteins. This phenotype was retained by the EAT-c/m cells which had been
      passaged repeatedly in mice. The most significant increase was in the content of
      sialic acid-containing glycoproteins found in the EAT-c cells. The sialic acid
      binding lectin Maackia amurensis leukoagglutinin (MAL) agglutinated all three EAT
      cell variants, while the sialic acid-binding Sambucus nigra (elderberry bark)
      lectin (SNA) agglutinated only the EAT-c and early-passage EAT-c/m cells. These
      findings indicate the presence of alpha 2,3-linked sialic acid on all three
      variants, but only the cultured cells and early-passage EAT-c/m cells possess the
      Neu5Ac alpha 2,6 linkage. The EAT-c cells attached avidly to wells coated with
      either laminin or fibronectin, as well as extracellular matrix produced by
      cultured bovine endothelial cells, but the EAT-wt and EAT-c/m cells did not.
      Paradoxically, the EAT-c cells were incapable of producing solid tumours when
      injected into a basement membrane-rich skeletal muscle bed, whereas the EAT-wt
      and EAT-c/m cells produced rapidly growing tumours when injected into the same
      environment. Lectin agglutination patterns established that ascitic tumour cells
      within the peritoneal cavity were derived from injected EAT-c cells.

PMID- 7827404
TI  - Carbohydrate receptor-mediated gene transfer to human T leukaemic cells.
AB  - The mucin-type carbohydrate Tn cryptantigen (GalNAc alpha 1-O-Ser/Thr, where
      GalNAc is N-acetyl-D-galactosamine) is expressed in many carcinomas, in
      haemopoietic disorders including the Tn syndrome, and on human immunodeficiency
      virus (HIV) coat glycoproteins, but is not expressed on normal, differentiated
      cells because of the expression of a Tn-processing galactosyltransferase. Using
      Jurkat T leukaemic cells which express high levels of Tn antigen due to deficient
      Tn galactosylation, we have established the Tn antigen-mediated gene transfer and
      demonstrate the considerable efficiency of this approach. We used poly(L-lysine)
      conjugates of the monoclonal antibody 1E3 directed against the Tn antigen to
      deliver the luciferase and beta-galactosidase reporter genes to Jurkat cells by
      receptor-mediated endocytosis. Addition of unconjugated 1E3 reduced transfection
      efficiency in a concentration-dependent manner and incubation with free GalNAc
      abolished DNA transfer completely, indicating that gene delivery is indeed
      mediated by the Tn antigen. Pre-treatment of Jurkat cells with Vibrio cholerae
      sialidase, which uncovers additional Tn antigens, resulted in an improvement of
      gene transfection. Both human and chicken adenovirus particles attached to the
      DNA/polylysine complex strongly augmented transgene expression. When the beta
      galactosidase (lacZ) gene was delivered to Jurkat cells by Tn-mediated
      endocytosis, up to 60% of the cells were positive in the cytochemical stain using
      5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-gal) as a chromogenic
      substrate. The efficiency of the transferrin receptor-mediated DNA uptake into
      Jurkat cells was comparatively low, although these cells were shown to express
      considerable amounts of transferrin receptor. We show here that a mucin-type
      carbohydrate antigen mediates highly efficient DNA uptake by endocytosis into
      Jurkat T cells. This method represents a 50-fold improvement of Jurkat cell
      transfection efficiency over other physical gene transfer techniques. Specific
      gene delivery to primary cancer cells exhibiting Tn epitopes may especially be
      desirable in immunotherapy protocols.

PMID- 7827405
TI  - Growth-related coordinate regulation of the early N-glycosylation genes in yeast.
AB  - The Saccharomyces cerevisiae ALG7, ALG1 and ALG2 genes, whose products function
      early in the dolichol pathway of protein N-glycosylation, are essential for cell
      viability, and perturbation in their expression causes G1-specific cell cycle
      arrest. Here, we show that expression of the ALG7, ALG1 and ALG2 genes is
      coordinately regulated at the G0/G1 transition point in the yeast life cycle.
      Carbon starvation, which induces cells to exit from the G1 stage of the mitotic
      cycle into G0, resulted in a time-dependent decrease in the levels of the early
      ALG genes' mRNAs. Accordingly, addition of glucose, which stimulates the G0
      arrested cells to resume proliferation, resulted in a rapid induction of their
      mRNAs. Cycloheximide alone also induced the early ALG transcripts, albeit to a
      much lower extent than glucose. Simultaneous addition of glucose and
      cycloheximide caused superinduction of these mRNAs, indicating that more than one
      control level was involved in their activation. Consistent with this, rapid
      degradation of ALG7, ALG1 and ALG2 mRNAs was completely abolished in the presence
      of cycloheximide. These data suggest that in yeast, the early N-glycosylation
      genes are regulated in a manner similar to that of the early growth-response
      genes.

PMID- 7827406
TI  - Characterization of a novel mouse recombinant processing alpha-mannosidase.
AB  - In previous work (Herscovics et al., J. Biol. Chem., 269, 9864-9871), a novel
      mouse alpha-mannosidase cDNA was isolated by homology, taking advantage of
      identical regions between the amino acid sequences of the yeast and rabbit liver
      processing alpha 1,2-mannosidases of different specificities to design degenerate
      oligonucleotides for reverse transcription/polymerase chain reaction. The cDNA
      isolated from a mouse 3T3 cDNA library encodes a 73 kDa type II membrane protein
      with a cytoplasmic region of approximately 35 amino acids and a large C-terminal
      region that contains a consensus Ca(2+)-binding sequence. To study the properties
      of this enzyme, the C-terminal part lacking the transmembrane region (beginning
      at either amino acid 106 or 171) was transiently expressed in COS cells as a
      secreted protein A fusion protein, and the enzymatic properties of the fusion
      protein bound to IgG-Sepharose were investigated. The enzyme is an alpha 1,2
      mannosidase that trims Man9GlcNAc to Man5 GlcNAc (where Man is mannose and GlcNAc
      is N-acetyl glucosamine). The activity requires divalent cations since it is
      greatly inhibited by ethylene diamine tetraacetic acid (EDTA). Although Ca2+ is
      the most effective, the enzyme may also use Mg2+, Mn2+ or Co2+, but not Zn2+,
      which is inhibitory. The enzyme is inhibited by 1-deoxymannojirimycin, but not by
      swainsonine. We propose that this novel alpha 1,2-mannosidase cDNA encodes mouse
      Golgi alpha-mannosidase IB.

PMID- 7827407
TI  - Structural features in heparin which modulate specific biological activities
      mediated by basic fibroblast growth factor.
AB  - The biological activity of basic fibroblast growth factor (bFGF) is influenced
      greatly by direct binding to heparin and heparan sulphate (HS). Heparin-derived
      oligosaccharides have been utilized to determine the structural requirements
      present in the polymer that account for binding to bFGF. We had previously
      demonstrated that fragments > 6 mer can inhibit the interaction between cell
      surface heparan sulphate proteoglycan (HSPG) and bFGF, and bFGF-induced
      proliferation of adrenocortical endothelial (ACE) cells. In contrast,
      oligosaccharides > 10 mer can enhance the binding of bFGF to its high-affinity
      receptor or support bFGF-induced mitogenesis in ACE cells (Ishihara et al., J.
      Biol. Chem., 268, 4675-4683, 1993). We have extended these studies to size- and
      structure-defined oligosaccharides from heparin, 2-O-desulphated (2-O-DS-)
      heparin, 6-O-desulphated (6-O-DS-) heparin, carboxy-reduced (CR-) heparin and
      carboxy-amidomethylsulphonated (AMS-) heparin. Oligosaccharides from these
      polymers were fractionated on a bFGF-affinity column and were assessed as
      inhibitors or enhancers of specific bFGF-derived biological activities. The
      results of these studies indicate that both 2-O-sulphate and the negative charge
      of the carboxy group [L-iduronic acid (IdoA) residues] are required for specific
      interactions of heparin-derived oligosaccharides with bFGF and for modulation of
      bFGF mitogenic activity. In addition, the charge of the carboxy groups in uronic
      acids can be replaced by other functional groups with a negative charge, such as
      the amidomethyl sulphonate moiety described here.

PMID- 7827408
TI  - Purification and immunohistochemistry of Griffonia simplicifolia agglutinin-II
      binding mucus glycoprotein in rat stomach.
AB  - Gastric mucus is thought to protect the gastric wall from mechanical trauma,
      desiccation, pathogenic microorganisms, acid and proteases. We purified Griffonia
      simplicifolia agglutinin-II (GSA-II)-binding mucus glycoprotein (GMG) from rat
      gastric mucosa by solubilization in a guanidine-containing buffer, gel permeation
      chromatography, Ricinus communis agglutinin-I (RCA-I)-affinity chromatography and
      GSA-II-affinity chromatography. Rat GMG showed high molecular weight on a
      Sephacryl S-1000 column, and a single band in 0.5% agarose-2% polyacrylamide
      composite gels and blots. A protein of approximately 60 kDa was contained in the
      GMG preparation. GMG was deglycosylated with trifluoromethanesulphonic acid
      treatment. An antibody was raised against deglycosylated GMG (deGMG). The
      antibody recognized deGMG, GMG, periodic acid-treated deGMG and O-glycanase
      digested deGMG, but did not react to trypsin-digested deGMG. These results
      suggest that the antibody recognizes proteinase-sensitive region or peptide
      backbone of GMG. In immunohistochemistry, the mucous gel layer of the stomach
      luminal surface was stained with antibody. The antibody recognized not only
      gastric mucous neck cells and pyloric gland cells, but also gastric surface
      mucous cells, mucous cells in the duodenal gland, and goblet cells in the small
      intestine and colon. These results indicate that GMG is a component of rat
      gastric mucus, and that the antibody recognizes mucous-secreting cells in rat
      stomach and intestine.

PMID- 7827409
TI  - Oligosaccharide profiles of HIV-2 external envelope glycoprotein: dependence on
      host cells and virus isolates.
AB  - The glycosylation pattern of the external envelope glycoprotein of human
      immunodeficiency virus type 2 (HIV-2) was studied in dependence on host cells and
      virus isolates. Strains HIV-2ALT, HIV-2ROD and HIV-2D194, differing in their
      biological properties and in the amino acid sequences of their env genes, were
      propagated in MOLT4, HUT78 and U937 cells, in human peripheral blood lymphocytes
      and monocytes/macrophages in the presence of [6-3H]glucosamine. Radiolabelled
      viral glycoproteins were isolated from the cell-free supernatants and digested
      with trypsin. Glycans were sequentially liberated by endo-beta-N
      acetylglucosaminidase H and peptide-N4-(N-acetyl-beta-glucosaminyl) asparagine
      amidase F, and fractionated according to charge and size. Comparison of the
      oligosaccharide profiles revealed that the envelope glycoproteins of different
      virus isolates, propagated in the same host cells, yielded very similar glycan
      patterns, whereas cultivation of an isolate in different host cells resulted in
      markedly divergent oligosaccharide maps. Variations concerned the proportion of
      high-mannose-, hybrid- and complex-type substituents, as well as the state of
      charge and structural parameters of the complex-type species. As a characteristic
      feature, complex-type glycans of macrophage-derived viral glycoprotein were
      almost exclusively substituted by lactosamine repeats. Hence, glycosylation of
      the HIV-2 external envelope glycoprotein seems to be primarily governed by host
      cell-specific factors rather than by the amino acid sequence of the corresponding
      polypeptide backbone.

PMID- 7827410
TI  - A novel 13C isotopic labelling strategy for probing the structure and dynamics of
      glycan chains in situ on glycoproteins.
AB  - A protocol is described for uniform 13C labelling of terminal galactose residues
      of the glycan chains of glycoproteins, using an enzymatic method which does not
      perturb the protein. The technique is illustrated by application to the
      biantennary N-linked glycan chains attached at Asn 297 of immunoglobulin G (IgG).
      Isotope-edited NMR experiments on this glycoprotein yield data which suggest that
      the galactose residues on the glycan exist in two discrete environments, with the
      galactose in one environment having greater mobility than that in the other.
      These data are qualitatively consistent with crystallographic data on an Fc
      fragment, which suggest that one arm of the glycan is in contact with the
      protein, while the other projects into the space between the C gamma 2 domains.
      Quantitatively, however, these data cannot be rationalized with the
      crystallographic data, which implies subtle differences in oligosaccharide
      structure and dynamics between the solution and crystal states of Fc.

PMID- 7827411
TI  - Human polyreactive and monoreactive antibodies: effect of glycosylation on
      antigen binding.
AB  - The present experiments were initiated to determine whether the carbohydrate
      portions of antibody molecules contribute to polyreactivity. Cell lines making
      human monoclonal polyreactive or monoreactive antibodies of the immunoglobulin
      (Ig) M, IgG and IgA isotypes were treated with tunicamycin to block N-linked
      glycosylation of the proteins. Analysis of the secreted native and non
      glycosylated proteins revealed a > 95% inhibition of [3H]mannose incorporation.
      Electrophoresis on sodium dodecyl sulphate-polyacrylamide gels of the proteins
      from tunicamycin-treated cells showed increased mobility and the absence of
      [3H]mannose incorporation of the immunoglobulin heavy chains, consistent with the
      lack of glycosylation. The native and non-glycosylated antibodies were then
      tested for their ability to bind different antigens. Despite the lack of
      glycosylation, both polyreactive and monoreactive antibodies bound to antigens
      with little if any loss of reactivity or specificity. It is concluded that the
      carbohydrate moieties do not contribute significantly to polyreactivity.

PMID- 7827412
TI  - Molecular dynamics simulations of high-mannose oligosaccharides.
AB  - Conformations of several high-mannose-type oligosaccharides that are generated
      during the biosynthetic degradation of Man9GlcNAc2 to Man5GlcNAc2 have been
      studied by molecular dynamics (MD). Simulations were performed on NCI-FCRDC's
      Cray Y-MP 8D/8128 supercomputer using Biosym's CVFF force field for 1000 ps with
      different initial conformations. The conformations of the two alpha 1,3- and the
      two alpha 1,6-linkages in each oligomannose were different, suggesting that
      deriving oligosaccharide conformations based on the conformational preferences of
      the constituent disaccharide fragments will not always yield correct results.
      Unlike other oligomannoses, Man9GlcNAc2 appears to take more than one distinct
      conformation around the core alpha 1,6-linkage. These various conformations may
      play an important role in determining the processing pathways. Using the data on
      the preferred conformations of these oligomannoses and the available experimental
      results, possible pathways for processing Man9GlcNAc2 to Man5GlcNAc2 by alpha 1,2
      linkage-specific mannosidases have been proposed. Conformational analysis of
      Man5GlcNAc2 indicates that the addition of beta 1,2-GlcNAc to the alpha 1,3
      linked core mannose, besides serving as a prerequisite for mannosidase II action
      as suggested earlier, may also prevent the removal of alpha 1,3-mannose. The MD
      simulations also suggest that the processing of the precursor oligosaccharide
      during Asn-linked complex and hybrid glycan biosynthesis proceeds in a well
      defined pathway involving more than one alpha 1,2-linkage-specific mannosidase.
      Knowledge of the conformation of the processing intermediates obtained from the
      present study can be used to design highly specific substrate analogues to
      inhibit a particular mannosidase, thereby blocking one processing pathway without
      interfering with the others.

PMID- 7827413
TI  - Identification, developmental expression and tissue distribution of
      deaminoneuraminate hydrolase (KDNase) activity in rainbow trout.
AB  - A deaminoneuraminosyl-glycohydrolase (KDNase), which catalyses the hydrolysis of
      alpha-ketosidic 2-keto-3-deoxy-D-glycero-D-galacto- nononic acid (or naturally
      occurring deaminated neuraminic acid; KDN) linkages in KDN-glycoconjugates, is
      required for their structural and functional studies since KDN residues are
      usually resistant to the action of known sialidases. A search for KDNase was
      initiated by examining various cells and tissues of rainbow trout because KDN
      glycoconjugates were first found in this animal species. Tissue localization
      studies of KDNase activity showed it to be present in kidney, spleen and ovary.
      The highest KDNase activity was found in ovarian post-ovulatory follicles
      obtained from female fish at the time when the reproductive organ was undergoing
      natural effacement. Little if any activity was found in brain, heart, liver,
      muscle, mature eggs and testis. Developmentally, higher levels of KDNase were
      usually expressed 3-4 months before ovulation or spermiation. An exception to
      this was in the ovary (or ovarian follicles) where the most striking increase in
      KDNase occurred 1-2 months after the maturation of gamete cells. Enzyme extracts
      containing KDNase activity also contained sialidase activity. From the data based
      on a kinetic study using mixed substrates, both KDNase and sialidase activities
      were indicated to reside on a single enzyme protein. The KDN-sialidase displayed
      broad specificity, which could possibly limit its usefulness as a probe for KDN
      glycoconjugates. Nevertheless, unlike sialidases, KDNase can selectively remove
      KDN residues, thus making it an important new reagent to identify KDN
      glycoconjugates in vivo.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7827414
TI  - Structure-function studies of oligosaccharides of recombinant human thyrotrophin
      by sequential deglycosylation and resialylation.
AB  - Recombinant human thyrotrophin (rhTSH) contains oligosaccharides terminating in 
      galactose-sialic acid, and had lower metabolic clearance and higher in vivo
      bioactivity compared to pituitary hTSH, which has oligosaccharides terminating
      predominantly in -N-acetylgalactosamine-sulphate. Previous studies using complete
      removal of the oligosaccharide chains showed an important role for the
      carbohydrate in the biological activity of the hormone. In the present study, we
      have determined the contribution of the individual monosaccharides to hormonal
      activity by sequential deglycosylation of rhTSH using exoglycosidases. We have
      also investigated the effect of resialylation of desialylated rhTSH using
      sialyltransferases. Sequential removal of sialic acid, galactose or N
      acetylglucosamine resulted in a > 10-fold increase in the in vitro bioactivity of
      rhTSH. The metabolic clearance of the derivatives was faster than that of intact
      hormone, but agalacto-rhTSH was cleared slower than asialo-rhTSH. However, the in
      vivo bioactivity decreased progressively with each monosaccharide removal. The
      increased cyclic AMP-stimulating activity, increased metabolic clearance and the
      decreased in vivo biologic activity were all reversed by resialylation of the
      terminal galactose residues. These results indicate that the in vitro, as well as
      the in vivo, bioactivities of rhTSH are modulated by terminal sialylation. The
      effects of sequential deglycosylation on the in vitro activity of rhTSH are
      different from those reported earlier for human chorionic gonadotrophin. Thus,
      modification of the oligosaccharides by glycosidases and glycosyltransferases can
      be used as a powerful tool to delineate the function of carbohydrate in
      glycoproteins and to engineer more potent hormone analogues with a longer half
      life and/or higher bioactivity.

PMID- 7827415
TI  - Structural studies on the oligosaccharides isolated from bovine kidney heparan
      sulphate and characterization of bacterial heparitinases used as substrates.
AB  - We prepared a series of oligosaccharides from commercial bovine kidney heparan
      sulphate after limited digestion with heparitinase I from Flavobacterium
      heparinum, and determined the structures of eight tetrasaccharides and a
      hexasaccharide by enzymatic analysis, fast atom bombardment mass spectrometry and
      500 MHz 1H NMR spectroscopy. The tetrasaccharides share the common core structure
      delta 4,5HexA alpha 1-4GlcN alpha 1-4HexA1-4GlcN (where delta 4,5HexA is 4-deoxy
      alpha-L-threo-hex-4-enopyranosyluronic acid and HexA is hexuronic acid), with
      zero, one or two sulphate groups. Seven of them contain non-sulphated glucuronic
      or iduronic acid, and the other, 2-O-sulphated iduronic acid at the internal
      position. Although they contain ordinary structures which should be widely
      distributed in the relatively low-sulphated region of heparan sulphate, five of
      the tetrasaccharides were isolated for the first time as discrete structures. The
      structure of the hexasaccharide was determined as delta 4,5HexA alpha 1-4GlcNAc
      alpha 1-4GlcA beta 1-3Gal beta 1-3Gal beta-1-4 Xyl and is derived from the
      carbohydrate-protein linkage region of the heparan sulphate chains. The
      hexasaccharide seems to have been released by the alkaline treatment used to
      prepare the heparan sulphate. The Gal residues were non-sulphated as are those in
      the porcine intestinal heparin chains, but in contrast to the sulphated Gal
      structures previously demonstrated in the carbohydrate-protein linkage region of
      chondroitin sulphate chains. These oligosaccharides were used to investigate the
      substrate specificity of heparitinases I and II from F. heparinum. The results
      revealed that heparitinase I cleaves hexosaminidic bonds linked to non-sulphated
      glucuronic or iduronic acid residues. The glucosaminidic linkage of the
      hexasaccharide was sensitive to heparitinase I, but resistant to heparitinase II,
      demonstrating the differential specificity of these enzymes towards the
      carbohydrate-protein linkage region.

PMID- 7827416
TI  - Simulating the process of malignant transformation.
AB  - A computationally efficient method for the simulation of carcinogenesis is
      presented. The underlying model for the process is the two-mutation clonal
      expansion model with explicit consideration of stochastic growth of malignant
      tumors. The usual likelihood-based methods of analysis ignore the growth kinetics
      of malignant tumors. The effect of this oversight on estimation of parameters is
      explored by simulation.

PMID- 7827417
TI  - Steady-state coexistence of three pure and simple competitors in a four-membered
      reactor network.
AB  - In this study we investigate the dynamics of pure and simple competition among
      three microbial populations in a spatially heterogeneous environment. The
      environment is modeled as a network of four interconnected bioreactors. Growth
      has been assumed to be noninhibitory, while maintenance requirements have been
      neglected. Results of numerical studies indicate that the three competitors may
      coexist in a stable steady state in a domain of the operating parameters space.
      Results are presented in the form of two-dimensional operating diagrams. No
      domain was found in the operating parameter space where more than one steady
      state is meaningful and stable. Since earlier theoretical studies have shown that
      two pure and simple microbial competitors may coexist in two interconnected
      bioreactors while numerical studies have shown that three pure and simple
      competitors cannot coexist in three interconnected bioreactors, the results of
      the present study may lead one to speculate the N pure and simple competitors may
      coexist in a network made of 2N-1 bioreactors.

PMID- 7827418
TI  - The shape of the size distribution of an epidemic in a finite population.
AB  - Qualitative changes in the shape of the distribution of the final size of the
      susceptible-->infected-->removed (S-I-R) epidemic are used by Nasell to define a
      threshold concept for the stochastic S-I-R epidemic. Numerical evaluations
      indicate that this threshold depends on the population size N according to the
      formula R0 approximately 1 + p/N1/3 for large N, where R0 is the basic
      reproduction ratio for the model. We derive an approximation of the final size
      distribution that supports this numerical result.

PMID- 7827419
TI  - Optimal drug regimens in cancer chemotherapy for single drugs that block
      progression through the cell cycle.
AB  - In this paper we study the application of a single drug in cancer chemotherapy
      where the drug can block progression through the cell cycle. Under certain
      conditions we determine the regimen that reduces the tumor population to a
      desired endpoint in minimal time while keeping a normal cell population above
      some lower limit. We also study the sensitivity of the optimal solution to
      various parameters.

PMID- 7827420
TI  - The agreement metric for labeled binary trees.
AB  - Let S be a set of n objects. A binary tree of S is a binary tree whose leaves are
      labeled without repetition from S. The operation of pruning a tree T is that of
      removing some leaves from T and suppressing all inner vertices of degree 2 which
      are formed by this deletion. Given two trees T and U, an agreement tree is a tree
      that can be obtained from T as well as from U by pruning the fewest number of
      leaves from the two trees. A quadratic algorithm is presented for doing this and
      two metrics are defined based on agreement trees.

PMID- 7827421
TI  - The basic reproduction ratio of HIV among intravenous drug users.
AB  - A new approach for the estimation of the Basic Reproduction Ratio R0 for HIV
      among intravenous drug users (IVDU) is proposed. This approach is based in an
      adaptation of the models proposed by Ross and Macdonald for vector-borne
      infections. A straightforward adaptation of Macdonald's model is presented first:
      biological vectors are replaced by needles and syringes and we consider a
      homogeneous population of IVDUs; next we present a modified model where several
      heterogeneities are considered. Some of those heterogeneities are due to
      intrinsic differences between needles and syringes and biological vectors;
      others, such as those related to movements of individuals between communities,
      should apply to both biological vectors and injection apparatuses. An example of
      the calculations of R0 for a real IVDUs community is presented.

PMID- 7827422
TI  - A clarification of the phi mixing model.
AB  - The authors review a deterministic model proposed for the analysis of two-way
      contingency tables that arise in counts of pairwise interactions. This model
      decomposes the table into the sum of two matrices with special forms: in one the
      contacts are distributed selectively, in the other they are distributed at
      random. We show that this model has several inherent problems. The decomposition
      is not unique, which compromises estimation and interpretation of the parameters;
      the deterministic framework provides no basis for estimation or hypothesis
      testing; and the assumption of decomposibility is supported by neither empirical
      evidence nor theoretical considerations. We show that generalized linear models
      provide a suitable alternative once the probability process is specified and the
      overparameterization is removed.

PMID- 7827423
TI  - A transmission model for a disease with some fatalities.
AB  - A stochastic epidemic model which allows some infected individuals to die from
      the disease is considered. The model includes the general epidemic and the fatal
      disease model as particular cases. A set of iterative equations is derived from
      which the probability distribution of the final size of the epidemic can be
      computed. It is illustrated that the fatal disease model is distinct in that it
      results in nearly all or hardly anyone being infected in a large population. An
      easily computed estimator for a key parameter of the model is derived and it is
      illustrated that it has good efficiency relative to the maximum likelihood
      estimator, which is very tedious to compute.

PMID- 7827424
TI  - Waning immunity and its effects on vaccination schedules.
AB  - A relatively comprehensive age-specific transmission model is used to determine
      the effect of various factors on the optimal vaccination ages in one-dose and two
      dose vaccination schedules. Motivated by the situation for measles, the model
      allows the duration of immunity of newborns to depend on the level of immunity of
      the mother at the time of the birth and allows for waning immunity as well as
      boosting of immunity by exposure to the disease. It is found that a significant
      amount of waning of disease-acquired immunity is plausible when boosting occurs
      but this is not an important factor in determining optimal vaccination schedules.
      On the other hand, plausible rates of loss of vaccine-induced immunity can have a
      substantial effect on the optimal vaccination schedule, particularly when there
      is no boosting of immunity. For two-dose schedules the optimal vaccination ages
      depend significantly on the level of vaccination coverage achieved. In the
      presence of plausible rates of loss of vaccine-induced immunity for measles, it
      is found that the vaccination coverage required to eradicate the disease is
      substantially higher than previously suggested.

PMID- 7827425
TI  - Some discrete-time SI, SIR, and SIS epidemic models.
AB  - Discrete-time models, or difference equations, of some well-known SI, SIR, and
      SIS epidemic models are considered. The discrete-time SI and SIR models give rise
      to systems of nonlinear difference equations that are similar in behavior to
      their continuous analogues under the natural restriction that solutions to the
      discrete-time models be positive. It is important that the entire system be
      considered since the difference equation for infectives I in an SI model has a
      logistic form which can exhibit period-doubling and chaos for certain parameter
      values. Under the restriction that S and I be positive, these parameter values
      are excluded. In the case of a discrete SIS model, positivity of solutions is not
      enough to guarantee asymptotic convergence to an equilibrium value (as in the
      case of the continuous model). The positive feedback from the infective class to
      the susceptible class allows for more diverse behavior in the discrete model.
      Period-doubling and chaotic behavior is possible for some parameter values. In
      addition, if births and deaths are included in the SI and SIR models (positive
      feedback due to births) the discrete models exhibit periodicity and chaos for
      some parameter values. Single-population and multi-population, discrete-time
      epidemic models are analyzed.

PMID- 7827426
TI  - Some bounds on estimates for reproductive ratios derived from the age-specific
      force of infection.
AB  - In this paper we shall look at estimation of reproductive ratios for common
      childhood infections such as chickenpox, measles, mumps, and hepatitis A with and
      without a vaccination program. The paper starts with a survey of previous work in
      this area. We suppose that we are given data in the form of an age-related
      serological profile with a given vaccination program. This is used to estimate
      the reproductive ratio and evaluate vaccination campaigns. The effect of
      different mixing patterns, such as homogeneous mixing, assortative mixing,
      proportional mixing, and symmetric mixing are discussed. R phi denotes the
      reproductive ratio when a steady-state vaccination campaign phi is used.
      Assortative mixing maximizes the reproductive ratio R phi. A mixing pattern which
      minimizes R phi and a lower bound for R phi for the important symmetric mixing
      case are found. The most usual situation is that we are given the age-serological
      profile with no vaccination so that we have bounds for the basic reproductive
      ratio R0. These results are illustrated with an application to vaccination
      against hepatitis A in Bulgaria. Numerical evaluations of the effect of different
      elimination vaccination strategies are examined.

PMID- 7827427
TI  - Clinical trial of aminotripa injection for total parenteral nutrition:
      multicenter comparative study with Hicaliq NC.

PMID- 7827428
TI  - Utility and sterility of TAB injection, an amino acid solution with carbohydrates
      and electrolytes for total parenteral nutrition, packaged in a dual-chambered
      plastic bag.

PMID- 7827429
TI  - Past, present, and future of nutritional support.

PMID- 7827430
TI  - Carbohydrate metabolism in parenteral nutrition.

PMID- 7827431
TI  - Nitrogen.

PMID- 7827432
TI  - Lipid for a parenteral use: development and future perspectives.

PMID- 7827433
TI  - Problems and prospectives in the antibiotic treatment of lower respiratory tract
      infections.

PMID- 7827434
TI  - Parasympatholytics in asthma.

PMID- 7827435
TI  - Use of selective agonists and antagonists to characterize tachykinin receptors
      mediating airway responsiveness in anaesthetized guinea-pigs.
AB  - Tachykinins are potent bronchoconstrictors. Here we have used novel highly
      selective agonists and antagonists to characterize tachykinin receptors mediating
      bronchoconstriction and hypotension in anaesthetized, paralysed guinea-pigs.
      Total lung resistance (RL) and dynamic lung compliance (Cdyn) were measured using
      an on-line, breath-by-breath method to analyse lung mechanics. The effects of iv
      injections of neuropeptide gamma (NP gamma), [Sar9,Met(O2)11]-SP (Sar-SP) (NK-1
      agonist), [Lys5,MeLeu9,Nle10]-NKA(4-10) (Lys-NKA) (NK-2 agonist) and senktide (NK
      3 agonist) were compared, before and after iv injection of the NK-1 antagonist CP
      96345 or the NK-2 antagonists MDL 29913 and SR 48968. NP gamma, Sar-SP and Lys
      NKA, but not senktide, increased RL and decreased Cdyn, accompanied by a fall in
      blood pressure (BP). The potency for increase of RL was Lys-NKA > NP gamma
      congruent to Sar-SP, for reduction of Cdyn was Lys-NKA = Sar-SP > NP gamma, and
      for fall in BP was Sar-SP > NP gamma >> Lys-NKA. CP 96345 (50 nmol/kg & 200
      nmol/kg) significantly antagonized the changes in RL, Cdyn and BP induced by Sar
      SP, and the fall in BP (but not changes in lung mechanics) in response to NP
      gamma, but did not alter any responses to Lys-NKA. In contrast, MDL 29913 (200
      nmol/kg & 10 mumol/kg) weakly and SR 48968 (100 nmol/kg) potently inhibited the
      effects on RL and Cdyn induced by Lys-NKA and NP gamma. Our results show that
      both NK-1 and NK-2 receptors are represented in guinea-pig airways. MDL 29913 is
      a weak NK-2 antagonist in guinea-pig airways compared to SR 48968. In addition,
      NK-1 but not NK-2 receptors appear to be important in mediating the hypotensive
      response to these tachykinins. In spite of its ability to cause a fall in BP via
      NK-1 receptors, NP gamma exerted its effects on RL and Cdyn solely via NK-2
      receptors.

PMID- 7827436
TI  - The antitussive effects of menthol, camphor and cineole in conscious guinea-pigs.
AB  - Menthol and other aromatic vapours have been widely used in the symptomatic
      treatment of upper respiratory tract infections, although there is little
      objective evidence as to their benefit. We have investigated the action of
      aromatic vapours on the cough reflex in conscious guinea-pigs. Animals (n = 13)
      were pretreated with air or test vapours for 5 min at a rate of 1 l/min. One
      minute later the animal was challenged with aerosolized citric acid for 2 min.
      Control responses to air pretreatment were not significantly different throughout
      the procedures. Three concentrations of each aromatic vapour were used (3, 10 and
      30 micrograms/l menthol, 50, 133 and 500 micrograms/l camphor and 0.8, 2.7 and 8
      mg/l cineole). Menthol proved the most effective antitussive--10 and 30
      micrograms/l produced a significant 28 and 56% reduction in cough frequency--500
      micrograms/l camphor gave a significant 33% reduction, while cineole, at the
      concentrations used, had no significant effect. An increase in cough latency
      coincided with a reduction in cough frequency. These results demonstrate the
      efficacy of aromatic vapours as antitussives in chemically induced cough.

PMID- 7827437
TI  - Multiple muscarinic receptor subtypes mediating pulmonary oedema in the rabbit.
AB  - The effects of various muscarinic antagonists on acetylcholine (ACh)-induced
      pulmonary oedema were studied in isolated perfused rabbit lungs. ACh induced a
      dose-dependent increase in the capillary filtration coefficient (Kf,c). This
      effect has been previously related to the activation of the capsaicin-sensitive
      nerve fibres and the release of substance P. Atropine, pirenzepine (M1-selective
      antagonist) and 4-DAMP (M3-selective antagonist) altered this response, producing
      a dose-dependent shift to the right of the ACh concentration-Kf,c response curve.
      By contrast, the M2-selective antagonist AFDX-116 shifted the ACh concentration
      response curve to the left. Atropine, pirenzepine and 4-DAMP also significantly
      reduced the capsaicin-induced increase in the Kf,c, while AFDX-116 enhanced it.
      We conclude that multiple muscarinic receptor subtypes are present in the rabbit
      lung, located on the C-fibres, and are involved in the ACh-induced pulmonary
      oedema. M1 and M3 receptors seem to stimulate the release of neuropeptides from C
      fibres, whereas M2 receptors have an inhibitory effect on these fibers.

PMID- 7827438
TI  - Levcromakalim- and isoprenaline-induced relaxation of human isolated airways-
      role of the epithelium and of K+ channel activation.
AB  - In this study we have investigated the mechanism of action of levcromakalim and
      isoprenaline in human isolated airways with respect to the K+ channels they
      activate and the possibility that these smooth muscle relaxants activate K+
      channels on the airway epithelium. Mechanical removal of the epithelial layer
      (mean percentage of epithelium present 20 +/- 3%, n = 20 tissues) did not affect
      the relaxation responses to levcromakalim or isoprenaline, either in terms of
      maximal relaxation or sensitivity. Whilst having no effect on isoprenaline
      induced relaxation, studied from basal tone, the ATP-sensitive K+ channel blocker
      BRL 31660 (10, 30 and 50 microM) reduced relaxation responses induced (from basal
      tone) by levcromakalim from 74 +/- 6% (of the maximal response to isoprenaline)
      to 48 +/- 12% (n = 7), 9 +/- 9% (n = 4) and 0 (n = 4), respectively.
      Charybdotoxin, a blocker of high conductance Ca(2+)-activated K+ channels, at
      concentrations of 30 and 100 nM, had no effect on either levcromakalim- or or
      isoprenaline-induced relaxation responses and yet charybdotoxin was active at KCa
      channels in outside-out patches of hippocampal granule cells. Moreover,
      tetraethylammonium (10 mM) inhibited neither isoprenaline- nor levcromakalim
      induced relaxation. This study has demonstrated that the relaxation responses
      elicited in human bronchus to isoprenaline and levcromakalim are likely to be the
      result of direct effects on the smooth muscle with no contribution from
      epithelial receptors or K+ channels. The actions of levcromakalim appear to be
      mediated only via activation of KATP channels. Further, we have made the
      important observation that, under the experimental conditions of our study,
      isoprenaline does not activate the KCa channel to produce relaxation in human
      bronchus.

PMID- 7827439
TI  - The significance of plasma progesterone levels during early pregnancies achieved
      after in vitro fertilization (IVF) treatment.
AB  - OBJECTIVE: Corpus luteum steroidogenesis is lower for in vivo ectopic pregnancy
      than for intrauterine pregnancy. There is a progesterone hallmark level
      distinguishing between viable intrauterine pregnancy and nonviable or ectopic
      pregnancy. This study attempts to answer whether this is also true for in vitro
      fertilization-treated patients. STUDY DESIGN: Using information retrieved from a
      computerized database, we compared the plasma 17 beta-estradiol (E2) and
      progesterone during the luteal phase and for every 2 to 3 days for several weeks
      during early pregnancy between those patients with proven ectopic pregnancies and
      those with singleton and multiple intrauterine pregnancies. Vaginal
      ultrasonography to detect an intrauterine gestational sac was performed from day
      19. A total of 73 pregnancies resulted from the replacement of fresh embryos in
      our in vitro fertilization-embryo transfer program. RESULTS: Only at day 10 post
      embryo transfer did those patients with ectopic pregnancy show statistically
      lower mean (SD) serum levels of E2 [2257 (SD, 2351) pmol/L] and plasma
      progesterone [PP; 221 (SD, 283) nmol/L] compared with patients with intrauterine
      pregnancy, whose mean E2 was 8846 (SD, 5871) pmol/L and mean PP was 805 (SD, 582)
      nmol/L (P = 0.008). For the rest of the follow-up until surgery was performed in
      ectopic pregnancy, there were no differences of statistical significance between
      extrauterine pregnancy and the intrauterine pregnancy groups. Furthermore, only
      on day 10 post embryo transfer, did we find a discriminatory zone (confidence
      interval, 95%) for E2 levels (903 to 3502 pmol/L for EP vs 6116 to 9493 pmol/L
      for a singleton and 4875 to 9493 pmol/L for multiple pregnancies). PP levels were
      26 to 283 nmol/L for ectopic pregnancy versus 496 to 1096 nmol/L for both
      singleton and multiple pregnancies. An intrauterine gestational sac was
      visualized at a mean of 23.2 (SD, 4) days after embryo transfer. On this day, the
      mean P levels were 982.6 (SD, 286.2) nmol/L for intrauterine and 804.5 (SD,
      502.4) nmol/L for ectopic pregnancies (P = NS). CONCLUSIONS: Except for day 10
      post embryo transfer, the steroidogenesis in ectopic pregnancy after in vitro
      fertilization treatment does not differ from successful intrauterine pregnancy.
      This observation negates an impaired steroidogenesis for ectopic pregnancy after
      in vitro fertilization and makes the PP level irrelevant in the diagnosis of
      pregnancy implantation.

PMID- 7827440
TI  - Angiotensin II (AII) modulation of steroidogenesis by luteinized granulosa cells
      in vitro.
AB  - PURPOSE: The purpose of the present study was to evaluate the effect of
      angiotensin II and its inhibitor, saralasin, on steroid production by luteinized
      human granulosa cells in vitro. Granulosa cells were obtained from follicular
      fluid aspirations from human in vitro fertilization. Cultures were established in
      supplemented Ham's F-10 medium. Human chorionic gonadotropin and angiotensin II
      were added to culture media and the effect on steroid production was measured.
      RESULTS: Human chorionic gonadotropin alone stimulated production of
      progesterone, estradiol, and testosterone. The addition of angiotensin II
      resulted in a dose-dependent increase in progesterone production (428% increase
      compared to baseline). No effect was seen on estradiol or testosterone. However,
      a large increase (700%) in estradiol was seen with the addition of the
      competitive inhibitor of angiotensin II, saralasin. CONCLUSION: We conclude that
      angiotensin II modulates progesterone production by human luteinized granulosa
      cells in vitro. The observed enhancement of estradiol production by angiotensin
      blockade suggests a tonic inhibition of estradiol secretion by endogenous
      angiotensin II.

PMID- 7827441
TI  - Visualization and cytogenetic analysis of second polar body chromosomes following
      its fusion with a one-cell mouse embryo.
AB  - PURPOSE: This study was designed to visualize the second polar body (2PB)
      chromosomes using its electrofusion with a one-cell-stage mouse embryo to
      approach preconception diagnosis of chromosomal disorders. RESULTS: Eighty to 90%
      hybridization efficiency has been achieved by electrofusion of 2PB with mouse
      zygotes. 2PB chromosomes were visualized in 40-50% of hybrids. Sixty-five percent
      of 2PB chromosomes were visualized when fused with the cytoplast obtained
      microsurgically by removing pronuclei from a one-cell embryo. As much as 33-43%
      of these resulting metaphases appeared to contain chromosomal aberrations. The
      follow-up of the development of the reconstructed one cell-stage hybrids in vitro
      revealed a significant decrease in their viability. The hybrid embryos resulting
      from 2PB electrofusion with enucleated zygotes did not develop beyond the two
      cell stage. CONCLUSION: Electrofusion is an efficient approach for hybridization
      of 2PB with a one-cell mouse embryo and may be useful for visualization and
      cytogenetic analysis of 2PB chromosomes. The visualization rate of 2PB
      chromosomes is higher if 2PB is fused with enucleated zygotes. However, the
      method induces over 30% of chromosomal aberrations and may lead to a significant
      decrease in the viability of the resulting one-cell embryos.

PMID- 7827442
TI  - Clinical experience with preimplantation diagnosis of sex by dual fluorescent in
      situ hybridization.
AB  - PURPOSE: Our purpose was to assess the clinical application of dual fluorescent
      in situ hybridization (FISH) for the diagnosis of sex in the human
      preimplantation embryo. RESULTS: Over a 2-year period, 18 couples at risk of
      transmitting X-linked recessive disorders underwent preimplantation diagnosis of
      embryo sex by dual FISH with X and Y chromosome-specific DNA probes. A total of
      27 in vitro fertilization (IVF) treatment cycles led to nine pregnancies; 7
      reached the stage of clinical recognition, of which 2 spontaneously aborted.
      There were five live births, three singleton and two twin: none in disagreement
      with the diagnosed sex. The diagnosis was corroborated in 51 of the 74
      nontransferred embryos. The efficiency of the procedure improved throughout the
      four treatment cycles. This was reflected in the increased proportion of double
      embryo transfers (from 50% in series 1 and 2 to 100% in series 3 and 4), with a
      consequent improvement in pregnancy rate (from 28 to 71% per embryo transfer).
      The excess of male embryos (male:female, 60:40 overall) and the high proportion
      of biopsied embryos with abnormal numbers of X and Y chromosome signals (14.5%)
      effectively reduced the number of normal female embryos available for transfer.
      CONCLUSION: Dual FISH is an efficient technique for determination of the sex of
      human preimplantation embryos and the additional ability to detect abnormal
      chromosome copy numbers, which is not possible via the polymerase chain reaction,
      (PCR), makes FISH the preferred technique.

PMID- 7827443
TI  - Complex genetic counseling and exclusion of Duchenne muscular dystrophy in a twin
      pregnancy after in vitro fertilization (IVF).
AB  - A twin pregnancy following in vitro fertilization-embryo transfer coincidentally
      at risk for the X-linked recessive Duchenne muscular dystrophy is described.
      First-trimester prenatal diagnosis by transabdominal chorionic villus samplings
      on the dichorionic placentae and molecular linkage analysis could exclude the
      disorder in both fetuses. Genetic counseling and prenatal diagnosis were
      particularly complex due to the twin pregnancy, the need for linkage analysis,
      and confined placental mosaicism 45,X/46XX in one of the fetuses. All parties
      should be aware that additional invasive diagnostic procedures in the second
      trimester might be required. It is proposed that, in similar situations, only
      one, arguably two, fertilized egg be transferred at a time to facilitate prenatal
      diagnosis and decision making for these rare couples. This problem, however, may
      be increasingly overcome by preimplantation diagnosis.

PMID- 7827444
TI  - Subzonal insemination (SUZI) or in vitro fertilization (IVF) in microdroplets for
      the treatment of male-factor infertility.
AB  - PURPOSE: The results of subzonal insemination (SUZI) and in vitro fertilization
      with microdroplet insemination used in couples with male-factor infertility are
      presented. RESULTS: The total fertilization rate was 17.4% for SUZI (n = 89) and
      49.3% for microdroplet IVF (n = 100). The fertilization rate for standard IVF (n
      = 510), not including any male-factor infertility and performed during the same
      period, was 73.2%. The "take-home baby rate" per started cycle and per embryo
      transfer (ET), respectively, was 10 and 17.6% for SUZI and 20 and 24.7% for
      microdrop IVF. For standard IVF these figures were 27 and 31.7%. CONCLUSION: It
      was concluded that microdroplet IVF can be used with good results in cases of
      moderate male-factor infertility. The normal (2PN) fertilization rate with the
      SUZI technique was only 15.1%. However, despite the low fertilization rate, SUZI
      should be considered when dealing with severe male-factor infertility.

PMID- 7827445
TI  - Successful freezing of unfertilized mouse oocytes and effect of cocultures in
      oviducts on development of in vitro fertilized embryos after thawing.
AB  - PURPOSE: To establish a freeze-thawing method for unfertilized oocytes with a
      high success rate, we examined several conditions for freeze-thawing. The effects
      of EDTA and cocultures in oviducts on the development of embryos fertilized in
      vitro after thawing were also studied. RESULTS: In the first experiment,
      unfertilized oocytes that were frozen in 1.5 M dimethylsulfoxide (DMSO)
      supplemented with 0.2 M sucrose by a slow freeze-thawing method showed the best
      results (fertilization rate, 71.9%; blastocyst rate per frozen oocyte, 18.8%).
      The proportion of embryos that developed to blastocysts was significantly higher
      when DMSO was added at 4 degrees C than at room temperature (39.4 vs 19.4%; P <
      0.01). The addition of EDTA (10 microM) to the culture medium did not promote
      embryo development after fertilization in vitro. However, the rate of development
      of in vitro fertilized embryos to blastocysts after thawing was significantly
      higher when the embryos were cultured in oviducts in vitro than the rates in
      control cultures and those cultured with EDTA (blastocyst rate from fertilized
      oocytes, 71.4 vs 51.0 and 52.8%, respectively; P < 0.01). CONCLUSION:
      Unfertilized mouse oocytes can be cryopreserved successfully by a slow freeze
      thawing method with the addition of 1.5 M DMSO and 0.2 M sucrose at low
      temperatures, and coculture with oviducts enhances the development of embryos
      that are fertilized in vitro after thawing.

PMID- 7827446
TI  - Effect of preincubation of human spermatozoa in milk on penetration of zona-free
      hamster oocytes: comparison to TEST yolk.
AB  - PURPOSE: To investigate the effect of preincubation of human sperm in milk on
      their ability to penetrate zona-free hamster oocytes, 27 ejaculates were studied.
      Each ejaculate was divided into two portions and incubated in either milk or TEST
      yolk (TESTY) for 22-24 hr at 5 degrees C prior to processing for the sperm
      penetration assay. RESULTS: Spermatozoa preincubated in milk penetrated a
      significantly (P < 0.05) higher percentage of oocytes (mean +/- SE; 74.4 +/- 6.3)
      than spermatozoa preincubated in TESTY (66.8 +/- 6.6). Statistically, no
      significant differences were noted for penetration index or postincubation sperm
      motility between the two media. CONCLUSION: Preincubation of sperm in milk
      therefore appears to enhance their ability to penetrate zona-free hamster
      oocytes, compared to TESTY preincubation. Since milk is natural, simple,
      inexpensive, readily available, and can be easily processed, it should be the
      medium of choice for sperm preincubation.

PMID- 7827447
TI  - Peptides extracted from Vero cell cultures overcome the blastocyst block of mouse
      embryos in a serum-free medium.
AB  - PURPOSE: The aim of this work was to evaluate the effect of a Vero cell coculture
      system on the development of mouse embryos. METHODS: Mouse embryos were randomly
      divided and cultured in human tubal fluid (HTF) medium with/without Vero cell
      monolayers, conditioned medium (CM) obtained from Vero cell cultures, and HTF
      medium supplemented with peptides extracted from CM. The concentrated CM was
      examined by SDS/PAGE. RESULTS: The development of mouse embryos was blocked at
      the blastocyst stage in pure HTF medium (1.4% hatching at day 5). This
      "blastocyst block" was overcome by coculture with Vero cell monolayers (48.1%
      hatching at day 5; 1.4 vs 48.1%; P < 0.001). CM and the addition of 5% fetal
      bovine serum (24.1 and 34.9% hatching, respectively, at day 5) were also able to
      enhance the process of hatching. In the other experiment, the addition of
      peptides extracted from Vero cell cultures also overcame the blastocyst block
      (12.5%) compared with pure HTF medium (2.1%) (P < 0.05). Electrophoretic
      separation revealed several classes of polypeptides consistently secreted into CM
      obtained from Vero cell cultures. Most peptides occurred in the M(r) range
      between 6.5 kd and 35.9 kd. CONCLUSION: A developmental block (blastocyst block)
      of mouse embryos in a serum- and protein-free medium (HTF) was discovered in this
      study. This block was effectively overcome by HTF plus serum and coculture with
      Vero cell monolayers and also by the peptides extracted from Vero cell
      conditioned medium. We speculate that certain factors secreted or converted by
      Vero cells may be critical in hatching of mouse embryos. Further study of these
      factors may be helpful in delineating its mechanism.

PMID- 7827448
TI  - Mycotoxin effects on in vitro preimplantation embryo development.

PMID- 7827449
TI  - Nurses bear the brunt of increased admissions for mental illness.

PMID- 7827450
TI  - Are the needs of informal carers still neglected in nursing practice?

PMID- 7827451
TI  - Assessing children's pain.
AB  - Children's experience of pain is difficult to assess. A number of tools are
      available that enable children's pain to be measured. If these are used
      appropriately, practitioners can set measurable goals for pain relief and
      evaluate their interventions.

PMID- 7827452
TI  - Evaluation of a hydrocellular dressing in the management of exuding wounds in the
      community.
AB  - A multicentre clinical trial was conducted to assess the performance and
      acceptability of a hydrocellular dressing in the management of exuding wounds by
      community nurses. The study examined ease of use, adherence, patient comfort,
      conformability and safety in use. Since this article was written, Allevyn
      hydrocellular dressing has become available on the Drug Tariff.

PMID- 7827453
TI  - Community psychiatric nursing: promoting health in a community setting.
AB  - With the development of care in the community, some mental health nurses have
      adopted approaches focused on health. This article explores one model of this
      approach which is aimed at secondary and tertiary health promotion in a community
      setting.

PMID- 7827454
TI  - Alzheimer's disease. 1: Pathology, aetiology and treatment.
AB  - Alzheimer's disease is a progressive disorder which accounts for a large
      proportion of people diagnosed with dementia. This article, the first in a two
      part series, discusses the pathology, aetiology and possible treatment of the
      condition.

PMID- 7827455
TI  - Examining the role of the practitioner-teacher in nursing.
AB  - This article examines the difficulties faced by specialist nurses when they
      attempt to combine practice and teaching roles. It gives a detailed analysis of
      the emergence of full-time practitioner-teachers in nursing, including the role
      of joint appointees. It is recommended that the practitioner-teacher role should
      be promoted, and this will necessitate research into the feasibility of such
      roles.

PMID- 7827456
TI  - 25 years of primary nursing.

PMID- 7827457
TI  - Patient involvement in resuscitation decisions.
AB  - The dilemma over whether patients should be involved in resuscitation decisions
      is a crucial issue as it brings into question some of the fundamental principles
      on which we base our practice. Nurses have a vital role to play in protecting
      patients' autonomy.

PMID- 7827459
TI  - Lessons to be learned from Colin Ralph's departure from the UKCC.

PMID- 7827458
TI  - Health issues and the Greek Cypriot woman.
AB  - This article aims to help health care workers begin to understand the Greek
      Cypriot woman, her needs, problems and strengths. It will try to explore briefly
      how Greek Cypriot women perceive health and illness and will discuss factors that
      influence these perceptions. It will also examine some of the major health
      problems that Greek Cypriot women face. The article uses material from the
      author's on-going research into the health needs of the Greek Cypriot community
      living in North London.

PMID- 7827460
TI  - Role of the nurse in the early stages of Alzheimer's disease.

PMID- 7827461
TI  - Prevention of pressure sores.
AB  - Pressure sores are undesirable. They have physical implications for patients,
      psychological and social implications for health care staff, relatives and
      patients, and financial implications for health services. Prevention is
      relatively simple and totally effective, so why does the incidence of pressure
      sores remain unacceptably high?

PMID- 7827462
TI  - Nursing management of a patient with burns.
AB  - The delivery of care required for a patient with burns is a multifaceted and
      challenging sphere of nursing practice. This article identifies the aims of
      treatment, highlighting the specific nursing care during the acute phase which is
      currently implemented on a regional burns unit.

PMID- 7827463
TI  - Educational issues in transcultural nursing.
AB  - Transcultural nursing education is an essential element of the nursing
      curriculum. There are a number of curriculum designs available but a combination
      of approaches seems to be the most desirable way forward.

PMID- 7827464
TI  - Promoting transcultural care in a college of health care studies.
AB  - This article describes the steps taken by the North London College of Health
      Studies to facilitate the development and delivery of culturally sensitive
      courses. It suggests that transcultural education for transcultural care can only
      truly be achieved if the organisational ethos, the epistemology which underpins
      the curriculum and the way that this is structured and taught, articulate
      together into a cohesive framework to enable the rhetoric to become reality.

PMID- 7827465
TI  - Learning from colleagues of different cultures.
AB  - Much can be learned about transcultural care from nursing colleagues who belong
      to minority ethnic groups. If they are willing and adequately empowered these
      nurses can become effective role models for their colleagues.

PMID- 7827466
TI  - ERASMUS cultural exchanges in Europe.
AB  - This article addresses the history and aims of the European Community's (EC)
      ERASMUS cultural exchange scheme for nursing students in higher education. It
      also examines the process of setting up an ERASMUS network, drawing on personal
      experience gained over the last 3 years, in order to help those who may be
      contemplating ERASMUS cultural exchanges for students and staff.

PMID- 7827467
TI  - Drug therapy and peptic ulceration.
AB  - Peptic ulceration can be treated by various types of drugs including antacids,
      protectors, antimicrobials and acid-secretion reducers. Nurses have a role to
      play in administering medicines, educating patients and, in future, prescribing
      drugs.

PMID- 7827468
TI  - What is clinical supervision?

PMID- 7827469
TI  - Alzheimer's disease 2: Caring for a woman with Alzheimer-type dementia.
AB  - Alzheimer's disease creates difficulties in perceiving and interpreting
      information for an individual. Nursing care must be sensitive to this. A
      comprehensive nursing assessment should include information about how the patient
      performed functionally and psychologically before the illness, and what these
      abilities are like on admission. This allows for achievable goals in care to be
      set. Although patients are cognitively impaired they should be actively involved
      in their care along with their carers.

PMID- 7827470
TI  - Quality, philosophy and Riehl's model of nursing.
AB  - It is theoretically possible to use Riehl's model of nursing as a vehicle for
      quality assurance. The individual's view of quality is a critical determinant.
      Patients should be partners in care, negotiating and instigating outcomes
      together with nurses whenever possible. A holistic approach and a humanistic
      philosophy for care in combination are important considerations in determining
      quality of care. Empowerment of the patient through an internal locus of control
      should enable care to be individualised. A patient thus empowered may then be
      able to assume responsibility for his/her health status.

PMID- 7827471
TI  - Ethics and accountability in nursing people with HIV infection.
AB  - This article considers ethical issues in relation to exercising accountability
      when nursing people with human immunodeficiency virus (HIV) infection or acquired
      immune deficiency syndrome (AIDS). A range of issues will be explored, some of
      which may be considered contentious.

PMID- 7827472
TI  - Intracranial pressure. Monitoring and management.
AB  - Monitoring of ICP from the subarachnoid, intraparenchymal, or ventricular spaces
      can be accomplished easily and reliably. The risks and benefits of each approach
      should be considered when choosing the monitoring technique. The goal of ICP
      management is to prevent herniation and to optimize cerebral perfusion. Even
      transient episodes of post-traumatic cerebral ischemia due to inadequate CPP can
      quickly nullify all resuscitative efforts. The provision of sufficient CBF is
      complicated by the varying degree of disruption of pressure autoregulation
      commonly resulting from head trauma. Post-injury, there is a need to provide a
      CPP which is elevated to some extent with respect to that sufficient in uninjured
      brains. This generally requires a CPP of at least 70 mm Hg, which must be
      accomplished by maintaining an adequate MAP while controlling ICH. Although ICH
      can generally be controlled using methods commonly employed, the majority of
      these techniques have potential complications. Additionally, there is increasing
      evidence that significant variation exists in the pathologic processes driving
      ICH in individual patients. Therefore, goals such as the desired CPP and
      conditions such as the relative contribution of edema, cerebral hypervolemia, and
      ischemia to ICH should optimally be considered in a patient-specific fashion and
      allow a targeted approach to therapy.

PMID- 7827473
TI  - Cerebral blood flow measurement in neurosurgical intensive care.
AB  - This article has addressed the rationale for the clinical measurement of CBF in
      the neuro-surgical ICU. The techniques that are currently available for
      measurement of CBF have been reviewed, and those that are particularly
      appropriate for ICU use have been highlighted. Several examples of the role of
      CBF monitoring in the management of ICU patients have been described, and these
      clinical situations are considered further in other articles in this issue
      regarding the management of patients with head injury and subarachnoid
      hemorrhage. These CBF monitoring techniques should be integrated with TCD and
      cerebral metabolism monitoring as described elsewhere in this issue. With further
      clinical experience and research and development in the area of neurosurgical
      critical care, CBF monitoring is almost certainly destined to become a routine
      and widely employed technique.

PMID- 7827474
TI  - Transcranial Doppler ultrasonography.
AB  - Transcranial Doppler ultrasonography is an extremely useful adjunct in
      neurosurgical intensive care. Continuous improvements in TCD equipment as well as
      computer software have improved examination success and also vessel
      identification. Recent expanding applications of TCD have also allowed the study
      of disorders of control of the cerebral circulation. TCD can be used to detect
      vessel narrowing from a variety of causes, including vasospasm, and also can be
      used to detect cerebral emboli and to evaluate CO2 reactivity, autoregulation,
      and the response to certain medications, as well as to indicate progressive
      obstruction of the cerebral circulation as seen in conditions leading to brain
      death. In the future, TCD may offer the ability to estimate the ICP using
      noninvasive means by evaluating velocity in the middle cerebral artery and
      arterial blood pressure tracings. The noninvasive determination of cerebral
      autoregulation may be useful in evaluating strategies to improve cerebral
      autoregulation as well as aid in the optimal management of ICP control and
      preservation of optimal cerebral circulation.

PMID- 7827475
TI  - Cerebral metabolism.
AB  - An intricate relationship normally exists between cerebral metabolism and energy
      substrate supply because of the brain's high substrate demand and limited storage
      capacity. In head-injured patients, this balance can be disrupted. The brain
      parenchyma directly involved by the injury is hypometabolic in respect to glucose
      and oxygen, whereas peri-injury tissue may have an elevated metabolic rate.

PMID- 7827476
TI  - Electroencephalograms and evoked potentials. Monitoring cerebral function in the
      neurosurgical intensive care unit.
AB  - Electroencephalographic and evoked potential testing are valuable clinical tools
      in the ICU. They can detect subclinical neurologic impairment, identify locations
      of dysfunction, and help establish the nature of some kinds of problems.
      Continuous monitoring provides a valuable technique for identifying nonconvulsive
      seizures, as well as for detecting certain complications early enough to
      intervene and prevent permanent sequelae. Knowledgeable clinicians can use these
      tools to benefit ICU patient care greatly.

PMID- 7827477
TI  - Integrated multimodality monitoring in the neurosurgical intensive care unit.
AB  - The selection of variables for continuous monitoring in the neurosurgical
      intensive care unit is based upon the requirement for constant perfusion and
      oxygenation of the brain and knowledge of the frequency and prognostic
      significance of abnormal values. Both arterial and intracranial pressure must be
      considered in the form of cerebral perfusion pressure. Body temperature and
      arterial oxygen saturation are essential to monitoring. Measurement of jugular
      venous oxygen saturation and cerebral blood flow velocity provide information of
      value in determining the source of raised intracranial pressure, the most
      appropriate means of treating it, and the safety of therapy.

PMID- 7827478
TI  - Status epilepticus. A perspective from the neuroscience intensive care unit.
AB  - Patients with GCSE and NCSE are common and may present to the emergency
      department or the NICU. In the NICU, NCSE is a more common presentation than
      GCSE. In the emergency department, GCSE commonly evolves to NCSE, either as a
      late sequela of prolonged SE or due to partial treatment with antiepileptic
      medication or neuromuscular blocking agents. In the emergency department, acute
      cerebral injuries are commonly found in patients presenting with SE, regardless
      of whether they have preexisting epilepsy. In the NICU, almost by definition, SE
      occurs in patients with acute cerebral injuries. Status epilepticus has been
      found to evolve sequentially through several stages, the end-point of which is a
      condition of refractory SE leading to neuronal necrosis and permanent cerebral
      injury. The responsiveness of SE to treatment is time-dependent. This makes early
      diagnosis and initiation of treatment essential. Most published treatment
      algorithms stress a 60-minute time window from the diagnosis of SE to its
      successful control. Unfortunately, the practical problem of patients with SE
      accessing such treatment protocols has been overlooked. Our preliminary
      (unpublished) data suggest that this access problem must be solved for treatment
      algorithms to improve the outcome of SE. In the NICU, access is less of a
      problem, and the determining factor is early diagnosis by NICU personnel. Because
      these patients usually sustain NCSE, which can be difficult to diagnose, a high
      index of suspicion and, optimally, continuous EEG monitoring are necessary for
      early diagnosis. NICU patients may be more susceptible to the ravages of SE
      because of their preexisting cerebral injuries. Expedited treatment may therefore
      be more important in this patient group. Clinical management of SE requires
      meticulous attention to ventilation and oxygenation, maintenance of adequate
      blood pressure, prevention of hyperthermia, and close monitoring for cardiac
      abnormalities. No specific medication is ideal for controlling SE. The
      knowledgeable and prompt use of intravenous lorazepam, a diazepam-phenytoin
      combination, or phenobarbital is acceptable as first-line treatment and as part
      of a systematic treatment algorithm. Refractory SE has been treated
      conventionally with high-dose intravenous barbiturate coma. Recent evidence
      suggests that high-dose intravenous midazolam may provide a useful alternative.

PMID- 7827479
TI  - Cerebral edema.
AB  - Cerebral edema continues to plague clinicians caring for patients with acute
      catastrophic neurologic disease. The defect responsible for the accumulation of
      water in the brain appears to reflect loss of the strict permeability barrier of
      the cerebral vasculature. A greater understanding of the physiologic mechanisms
      at work in the blood-brain barrier have helped target therapies at the vascular
      interface between the circulating blood and the brain. The mounting evidence
      which implicates inflammatory events as causally related to the loss of
      cerebrovascular impermeability supports the clinical strategy of suppression of
      acute inflammation. Clearly, further advances in the management of cerebral edema
      will be strongly influenced by the development of specific anti-inflammatory
      pharmaceuticals.

PMID- 7827480
TI  - Fluid and electrolyte disorders in neurosurgical intensive care.
AB  - The management of fluid and electrolytes is an important aspect of the intensive
      care of patients with intracranial disease and injury because the central nervous
      system has a critical role in fluid and electrolyte and acid-base homeostasis.
      This article reviews fluids and electrolytes and acid-base balance, their common
      disturbances in neurosurgical disorders, and their practical management.

PMID- 7827481
TI  - Cardiac performance enhancement and hypervolemic therapy.
AB  - This article discusses guidelines the authors have established in managing
      patients with ruptured intracranial aneurysms and associated vasospasm. These
      guidelines represent methods of improving cardiac output or the ideal cardiac
      indices, to improve or maximize cerebral blood flow and potentially improve
      outcome. The guidelines for hypervolemic therapy for the volume and timing of
      intravenous fluid administration and the target cardiac performance parameters
      also are discussed.

PMID- 7827482
TI  - Infections in the neurosurgical intensive care unit.
AB  - The sources of fever and infection in neurosurgical patients in the intensive
      care unit are varied and complex. Benign postoperative fever due to atelectasis
      of the lungs or from central nervous system sources are difficult to define.
      Distinguishing between these "benign" sources and true nosocomial bacterial
      infections can be a difficult clinical process. Empiric antibiotic regimens are
      outlined, and some guidelines are proposed for the management of infected
      catheters.

PMID- 7827483
TI  - Intensive care of patients with spinal trauma.
AB  - This article takes a systematic approach to intensive care unit management of
      acute spinal cord injury. Pathophysiology and current medical management of the
      neurologic injury are discussed. Anticipation, prevention, and treatment of
      sequelae of spinal cord injury are stressed in sections on respiratory,
      cardiovascular, venous thrombosis, and gastrointestinal issues, as well as in
      sections on nutritional, genitourinary, and skin problems associated with spinal
      cord injury.

PMID- 7827484
TI  - Critical care of patients with subarachnoid hemorrhage.
AB  - Critical care of a patient with SAH should focus on the prevention or immediate
      treatment of the common sequelae of this disorder that adversely affect outcome:
      vasospasm, rebleeding, hydrocephalus, seizures, and associated medical problems.
      The frequency of rebleeding can be lessened by early surgical or endovascular
      intervention. The extent of SAH on the CT scan can identify those patients at
      highest risk for vasospasm, and all patients must be closely monitored in the ICU
      with serial neurological examinations and transcranial Doppler studies. Regional
      CBF examinations and continuous EEG may also be helpful. Calcium channel blocking
      agents and volume expansion are recommended prophylatically for all patients.
      Aggressive hypertensive, hemodilutional, hypervolemic therapy (including
      pulmonary artery catheter placement) is indicated for symptomatic vasospasm.
      Transluminal angioplasty can be used in selected patients with vasospasm
      refractory to these measures. Hydrocephalus can occur in the days, weeks, or
      months following SAH and is treated effectively with external (acute
      hydrocephalus) or internal cerebrospinal fluid diversion. Seizures, which can
      cause intracranial and systemic hypertension, high cerebral metabolic demand, and
      delayed neurological injury, should be prevented with prophylactic use of
      anticonvulsants. In addition, early recognition and treatment of associated
      medical complications are critical. Novel endovascular approaches, meticulous
      surgical technique, and aggressive ICU care will undoubtedly lead to improved
      outcome following aneurysmal SAH.

PMID- 7827485
TI  - Neurosurgical postoperative care.
AB  - The goals of postoperative neurosurgical intensive care are early detection of
      neurologic deterioration and maintenance or reestablishment of systemic and
      neurologic homeostatsis. Encompassed within these goals is an effort to prevent
      postoperative complications or to minimize their impact once they have occurred.
      This article focuses on postoperative care following intracranial surgery.
      Criteria for admission to the intensive care unit are discussed.

PMID- 7827486
TI  - Computer applications in the intensive care unit.
AB  - Incorporating computers into all aspects of daily ICU operations is a formidable
      task both technically and logistically. To coordinate a project as complex as
      this, it is imperative to achieve close cooperation between physicians, nurses,
      basic scientists, computer specialists, hospital administrators, and equipment
      manufacturers. In this article, we have provided a blueprint and have discussed
      the implementation of a COmputational Model of PATient Health Status (COMPATHS)
      designed to carry out such integration.

PMID- 7827487
TI  - The neurosurgical intensive care unit in an era of health care reform.
AB  - Health care reform, public concern, and managed care will create an environment
      that demands highly creative strategies to deliver quality care while reducing
      costs. Patient satisfaction and outcomes will take on a high priority. To meet
      this challenge, the neurosurgical ICU of the future will be designed with a
      patient-focused theme wherein the physical environment embodies healing and
      humanism. Services will be brought to the patient rather than the patient
      accommodating the system. Patients and families will be the directors of their
      own care. Staff and families will have access to a highly sophisticated clinical
      information system, and learning for staff at all levels will be a part of
      everyday life in the ICU. Unit management will be within a framework of shared
      governance wherein the power base is with the direct care givers, and decision
      and policy making happens at the point closest to the patient. Patient outcomes
      will be a result of a highly organized collaborative model that includes primary
      nursing, critical paths, and case management. Partnerships between nurses and
      unit support staff will create skill-mix changes that allow the nurse to spend
      less time on nonclinical unit maintenance-type functions and more time with the
      patient and family. This will have a positive fiscal impact as well as enhance
      patient satisfaction and outcomes.

PMID- 7827488
TI  - GRP2 proteins contain both CCHC zinc fingers and a cold shock domain.

PMID- 7827489
TI  - Emerging themes of plant signal transduction.

PMID- 7827490
TI  - A member of the tomato Pto gene family confers sensitivity to fenthion resulting
      in rapid cell death.
AB  - Leaves of tomato cultivars that contain the Pto bacterial resistance locus
      develop small necrotic lesions within 24 hr after exposure to fenthion, an
      organophosphorous insecticide. Recently, the Pto gene was isolated and shown to
      be a putative serine/threonine protein kinase. Pto is one member of a multigene
      family that is clustered within a 400-kb region on chromosome 5. Here, we report
      that another member of this gene family, termed Fen, is responsible for the
      sensitivity to fenthion. Fen was isolated by map-based cloning using closely
      linked DNA markers to identify a yeast artificial chromosome clone that spanned
      the Pto region. After transformation with the Fen gene under control of the
      cauliflower mosaic virus (CaMV) 35S promoter, tomato plants that are normally
      insensitive to fenthion rapidly developed extensive necrotic lesions upon
      exposure to fenthion. Two related insecticides, fensulfothion and fenitrothion,
      also elicited necrotic lesions specifically on Fen-transformed plants. Transgenic
      tomato plants harboring integrated copies of the Pto gene under control of the
      CaMV 35S promoter displayed sensitivity to fenthion but to a lesser extent than
      did wild-type fenthion-sensitive plants. The Fen protein shares 80% identity (87%
      similarity) with Pto but does not confer resistance to Pseudomonas syringae pv
      tomato. These results suggest that Pto and Fen participate in the same signal
      transduction pathway.

PMID- 7827491
TI  - Arabidopsis TCH3 encodes a novel Ca2+ binding protein and shows environmentally
      induced and tissue-specific regulation.
AB  - The Arabidopsis touch (TCH) genes are up-regulated in response to various
      environmental stimuli, including touch, wind, and darkness. Previously, it was
      determined that TCH1 encodes a calmodulin; TCH2 and TCH3 encode calmodulin
      related proteins. Here, we present the sequence and genomic organization of TCH3.
      TCH3 is composed of three repeats; remarkably, the first two repeats share 94%
      sequence identity, including introns that are 99% identical. The conceptual TCH3
      product is 58 to 60% identical to known Arabidopsis calmodulins; however, unlike
      calmodulin, which has four Ca2+ binding sites, TCH3 has six potential Ca2+
      binding domains. TCH3 is capable of binding Ca2+, as demonstrated by a Ca(2+)
      specific shift in electrophoretic mobility. 5' Fragments of the TCH3 locus, when
      fused to the beta-glucuronidase (GUS) reporter gene, are sufficient to confer
      inducibility of expression following stimulation of plants with touch or
      darkness. These TCH3 sequences also direct expression to growing regions of
      roots, vascular tissue, root/shoot junctions, trichomes, branch points of the
      shoot, and regions of siliques and flowers. The pattern of expression of the
      TCH3/GUS reporter genes most likely reflects expression of the native TCH3 gene,
      because immunostaining of the TCH3 protein shows similar localization. The tissue
      specific expression of TCH3 suggests that expression may be regulated not only by
      externally applied mechanical stimuli but also by mechanical stresses generated
      during development. Consequently, TCH3 may perform a Ca(2+)-modulated function
      involved in generating changes in cells and/or tissues that result in greater
      strength or flexibility.

PMID- 7827492
TI  - Regulation of gene expression programs during Arabidopsis seed development: roles
      of the ABI3 locus and of endogenous abscisic acid.
AB  - The accumulation kinetics of 18 mRNAs were characterized during Arabidopsis
      silique development. These marker mRNAs could be grouped in distinct classes
      according to their coordinate temporal expression in the wild type and provided a
      basis for further characterization of the corresponding regulatory pathways. The
      abscisic acid (ABA)-insensitive abi3-4 mutation modified the expression pattern
      of several but not all members of each of these wild-type temporal mRNA classes.
      This indicates that the ABI3 protein directly participates in the regulation of
      several developmental programs and that multiple regulatory pathways can lead to
      the simultaneous expression of distinct mRNA markers. The ABI3 gene is
      specifically expressed in seed, but ectopic expression of ABI3 conferred the
      ability to accumulate several seed-specific mRNA markers in response to ABA in
      transgenic plantlets. This suggested that expression of these marker mRNAs might
      be controlled by an ABI3-dependent and ABA-dependent pathway(s) in seed. However,
      characterization of the ABA-biosynthetic aba mutant revealed that the
      accumulation of these mRNAs is not correlated to the ABA content of seed. A
      possible means of regulating gene expression by developmental variations in ABA
      sensitivity is apparently not attributable to variations in ABI3 cellular
      abundance. The total content of ABI3 protein per seed markedly increased at
      certain developmental stages, but this augmentation appears to result primarily
      from the simultaneous multiplication of embryonic cells. Our current findings are
      discussed in relation to their general implications for the mechanisms
      controlling gene expression programs in seed.

PMID- 7827493
TI  - The barley stripe mosaic virus gamma b gene encodes a multifunctional cysteine
      rich protein that affects pathogenesis.
AB  - Barley stripe mosaic virus contains seven genes, one of which specifies a 17-kD
      cysteine-rich protein, gamma b, that is known to affect virulence. To further
      characterize the role of gamma b in pathogenesis, we mutagenized sequences
      encoding amino acids within two clusters of cysteine and histidine residues in
      the cysteine-rich domain and a group of basic amino acids located between the
      clusters and determined the effects of these mutations on the symptom phenotype
      in barley. Three single amino acid substitutions in cluster 1 and two amino acid
      exchanges in the basic region caused bleached symptoms associated with pronounced
      elevations in accumulation of gamma b protein. In contrast, three single amino
      acid substitutions in cluster 2 and a mutation in the basic motif resulted in
      attenuated ("null") symptoms typical of those produced when the gamma b gene is
      deleted. Tissue infected with these "null" mutants accumulated slightly elevated
      amounts of the gamma b protein but significantly lower levels of coat protein and
      the putative movement protein beta b. Genetic complementation tests revealed that
      cluster 1 mutations are dominant over the wild-type gamma b gene, whereas those
      in cluster 2 are recessive. These results highlight the pivotal role of gamma b
      in pathogenesis and suggest that the two cysteine-rich clusters are functionally
      distinct and that they affect different aspects of disease development.

PMID- 7827494
TI  - Functional analysis of a light-responsive plant bZIP transcriptional regulator.
AB  - Common plant regulatory factor 1 (CPRF1) is a parsley basic region/leucine zipper
      (bZIP) transcription factor that recognizes specific nucleotide sequences
      containing ACGT cores. Such a sequence is contained within LRU1, the composite
      light regulatory unit that is necessary and sufficient for light-dependent
      activity of the parsley chalcone synthase (CHS) promoter. After light treatment
      of both etiolated and green seedlings, CPRF1 mRNA levels increased prior to CHS
      mRNA accumulation. The change in CPRF1 mRNA leads to a light-responsive increase
      in CPRF1 protein. Transient expression analysis in parsley protoplasts using the
      CPRF1 promoter fused to the beta-glucuronidase (GUS) open reading frame indicated
      that light-dependent CPRF1 mRNA accumulation was under transcriptional control.
      The 5' untranslated region of the CPRF1 gene includes a cis-acting nucleotide
      sequence that contains two ACGT elements at a distance of 12 bp between their
      palindromic centers. This feature is reminiscent of as-1 and octopine synthase
      (ocs) elements identified in promoters from plant pathogens. This double ACGT
      Element element, designated dACECPRF1, stimulated transcription when placed 5' to
      a heterologous core promoter. CPRF1 bound to dACECPRF1 DNA as well as to the ACGT
      element from the CHS promoter in vitro. Cotransfection experiments demonstrated
      that CPRF1 interacts with these elements in vivo and that overexpression of CPRF1
      actually reduced light-dependent transcription from the CHS promoter. CPRF1 thus
      appears to contribute to the regulation of the CPRF1 gene and to interfere with
      the activities of light-regulated promoters.

PMID- 7827495
TI  - Reduction of tomato polygalacturonase beta subunit expression affects pectin
      solubilization and degradation during fruit ripening.
AB  - The developmental changes that accompany tomato fruit ripening include increased
      solubilization and depolymerization of pectins due to the action of
      polygalacturonase (PG). Two PG isoenzymes can be extracted from ripe fruit: PG2,
      which is a single catalytic PG polypeptide, and PG1, which is composed of PG2
      tightly associated with a second noncatalytic protein, the beta subunit. Previous
      studies have correlated ripening-associated increases in pectin solubilization
      and depolymerization with the presence of extractable PG1 activity, prior to the
      appearance of PG2, suggesting a functional role for the beta subunit and PG1 in
      pectin metabolism. To assess the function of the beta subunit, we produced and
      characterized transgenic tomatoes constitutively expressing a beta subunit
      antisense gene. Fruit from antisense lines had greatly reduced levels of beta
      subunit mRNA and protein and accumulated < 1% of their total extractable PG
      activity in ripe fruit as PG1, as compared with 25% for wild type. Inhibition of
      beta subunit expression resulted in significantly elevated levels of EDTA-soluble
      polyuronides at all stages of fruit ripening and a significantly higher degree of
      depolymerization at later ripening stages. Decreased beta subunit protein and
      extractable PG1 enzyme activity and increased pectin solubility and
      depolymerization all cosegregated with the beta subunit antisense transgene in T2
      progeny. These results indicate (1) that PG2 is responsible for pectin
      solubilization and depolymerization in vivo and (2) that the beta subunit protein
      is not required for PG2 activity in vivo but (3) does play a significant role in
      regulating pectin metabolism in wild-type fruit by limiting the extent of pectin
      solubilization and depolymerization that can occur during ripening. Whether this
      occurs by direct interaction of the beta subunit with PG2 or indirectly by
      interaction of the beta subunit with the pectic substrate remains to be
      determined.

PMID- 7827496
TI  - Isolation of the protein backbone of an arabinogalactan-protein from the styles
      of Nicotiana alata and characterization of a corresponding cDNA.
AB  - Arabinogalactan-proteins (AGPs) from the styles of Nicotiana alata were isolated
      by ion exchange and gel filtration chromatography. After deglycosylation by
      anhydrous hydrogen fluoride, the protein backbones were fractionated by reversed
      phase HPLC. One of the protein backbones, containing mainly hydroxyproline,
      alanine, and serine residues (53% of total residues), was digested with
      proteases, and the peptides were isolated and sequenced. This sequence
      information allowed the cloning of a 712-bp cDNA, AGPNa1. AGPNa1 encodes a 132
      amino acid protein with three domains: an N-terminal secretion signal sequence,
      which is cleaved from the mature protein; a central sequence, which contains most
      of the hydroxyproline/proline residues; and a C-terminal hydrophobic region.
      AGPNa1 is expressed in many tissues of N. alata and related species. The
      arrangement of domains and amino acid composition of the AGP encoded by AGPNa1
      are similar to that of an AGP from pear cell suspension culture filtrate,
      although the only sequence identity is at the N termini of the mature proteins.

PMID- 7827497
TI  - Elements of the maize A1 promoter required for transactivation by the anthocyanin
      B/C1 or phlobaphene P regulatory genes.
AB  - The extensive genetic and molecular characterization of the flavonoid pathway's
      structural and regulatory genes has provided some of the most detailed knowledge
      of gene interactions in plants. In maize flavonoid biosynthesis, the A1 gene is
      independently regulated in the anthocyanin and phlobaphene pathways. Anthocyanin
      production requires the expression of the C1 or PI and R or B regulatory genes,
      whereas phlobaphene production requires only the P regulatory gene. By deletion
      analysis of the A1 promoter, we show that the sequences between -123 and -88 are
      critical for activation by anthocyanin and phlobaphene regulatory genes. Linker
      scanner mutations indicated that the -123 to -100 region is more important for
      transactivation by the P protein. The -98 to -88 region is more important for
      B/C1 transactivation and shows a strong homology with the region of the Bz1
      anthocyanin structural gene promoter shown to be activated by B/C1 and not by P.
      We identified a 14-bp consensus sequence that is also present in the promoters of
      three other genes in the anthocyanin pathway, and we propose a model for how the
      flavonoid regulatory proteins interact with the promoters of the structural
      genes.

PMID- 7827498
TI  - Sugar sensing in higher plants.
AB  - Sugar repression of photosynthetic genes is likely a central control mechanism
      mediating energy homeostasis in a wide range of algae and higher plants. It
      overrides light activation and is coupled to developmental and environmental
      regulations. How sugar signals are sensed and transduced to the nucleus remains
      unclear. To elucidate sugar-sensing mechanisms, we monitored the effects of a
      variety of sugars, glucose analogs, and metabolic intermediates on photosynthetic
      fusion genes in a sensitive and versatile maize protoplast transient expression
      system. The results show that sugars that are the substrates of hexokinase (HK)
      cause repression at a low concentration (1 to 10 mM), indicating a low degree of
      specificity and the irrelevance of osmotic change. Studies with various glucose
      analogs suggest that glucose transport across the plasma membrane is necessary
      but not sufficient to trigger repression, whereas subsequent phosphorylation by
      HK may be required. The effectiveness of 2-deoxyglucose, a nonmetabolizable
      glucose analog, and the ineffectiveness of various metabolic intermediates in
      eliciting repression eliminate the involvement of glycolysis and other metabolic
      pathways. Replenishing intracellular phosphate and ATP diminished by hexoses does
      not overcome repression. Because mannoheptulose, a specific HK inhibitor, blocks
      the severe repression triggered by 2-deoxyglucose and yet the phosphorylated
      products per se do not act as repression signals, we propose that HK may have
      dual functions and may act as a key sensor and signal transmitter of sugar
      repression in higher plants.

PMID- 7827499
TI  - A fusicoccin binding protein belongs to the family of 14-3-3 brain protein
      homologs.
AB  - The fusicoccin binding protein (FCBP) is a highly conserved plasma membrane
      protein present in all higher plants tested thus far. It exhibits high- and low
      affinity binding for the fungal toxin fusicoccin (FC). We purified the active
      FCBP from a fraction highly enriched in plasma membrane by selective
      precipitation and anion exchange chromatography. After SDS-PAGE, the two FCBP
      subunits of 30 and 31 kD were detected as major bands. Amino acid sequence
      analysis of the 31-kD polypeptide displayed a high degree of identity with so
      called 14-3-3 proteins, a class of mammalian brain proteins initially described
      as regulators of neurotransmitter synthesis and protein kinase C inhibitors.
      Thereafter, we affinity purified the 30- and 31-kD FCBP subunits, using
      biotinylated FC in combination with a monomeric avidin column. Immunodecoration
      of these 30- and 31-kD FCBP subunits with polyclonal antibodies raised against a
      14-3-3 homolog from yeast confirmed the identity of the FCBP as a 14-3-3 homolog.
      Similar to all 14-3-3 protein homologs, the FCBP seems to exist as a dimer in
      native form. Thus far, the FCBP is the only 14-3-3 homolog with a receptor-like
      function. The conserved structure of the 14-3-3 protein family is a further
      indication that the FCBP plays an important role in the physiology of higher
      plants.

PMID- 7827500
TI  - Purification and structural characterization of porcine L-threonine
      dehydrogenase.
AB  - L-Threonine dehydrogenase was purified 10,000-fold to a specific activity
      approximately 300 mumol.min-1.mg-1 protein from porcine liver mitochondria.
      Purification to apparent homogeneity was achieved by sequential chromatography on
      DEAE Sepharose FF, Affi-Gel Blue, Sephacryl S-200, Matrex Gel Red A, and Matrex
      Gel Green A. The subunit molecular mass was estimated as 37 kDa by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis, while an apparent native molecular
      mass of 73 kDa was shown by gel filtration chromatography, suggesting a dimeric
      structure. The purified enzyme was subjected to proteolytic degradation and the
      resulting peptides were isolated exclusively by reverse-phase high-performance
      liquid chromatography. Approximately 70% of the total sequence was obtained and
      the N-terminal amino acid sequence of the intact polypeptide chain was thus
      tentatively extended to residue 40.

PMID- 7827501
TI  - A fast method for obtaining highly pure recombinant herpes simplex virus type 1
      thymidine kinase.
AB  - Recombinant Herpes Simplex Virus Type 1 thymidine kinase (TK) was isolated in a
      fast and gentle two-step procedure from Escherichia coli as a thrombin cleavable
      fusion protein. The TK was expressed as an inducible glutathione S-acetyl
      transferase fusion protein and purified in a first step by glutathione affinity
      chromatography. Proteolytic cleavage of the column bound TK with thrombin led to
      a truncated enzyme, resulting from two new and hitherto unknown cleavage sites,
      determined by N-terminal sequencing. In a second step, the TK was further
      purified from the cleavage products by ATP affinity chromatography, yielding
      homogeneously pure TK as shown by SDS-PAGE and mass spectrometry. Both the fusion
      protein and the purified enzyme show enzymatic activity with the same Km value of
      0.2 microM for the natural substrate thymidine. Determination of the native
      molecular weight indicated that the pure enzyme and the fusion protein are
      biologically active as homodimers. Therefore the recombinant enzyme has the same
      biochemical characteristics as the viral TK, expressed in infected cells.

PMID- 7827502
TI  - Expression of human cystathionine beta-synthase in Escherichia coli: purification
      and characterization.
AB  - Cystathionine beta-synthase (CBS) purification from mammalian tissues is
      complicated by proteolysis and enzyme aggregation. To surmount these
      difficulties, we cloned human CBS cDNA in tandem with the beta-galactosidase
      sequence of the fusion vector, pAX5-, then expressed the fusion protein, beta
      galactosidase/CBS, in transformed Escherichia coli cells. Proteolytic treatment
      of the ammonium sulfate fraction of bacterial lysates with endoproteinase Xa
      liberated CBS which could then be separated from its fusion partner by DEAE
      cellulose chromatography. This nearly homogeneous enzyme preparation was purified
      140-fold over the crude bacterial lysate with nearly 50% recovery, and its
      specific activity, 210 U/mg protein, was comparable to that purified from human
      liver. The purified enzyme contained pyridoxal 5'-phosphate and exhibited
      positive cooperativity toward S-adenosyl-L-methionine (Hill coefficient = 5.2;
      Kact = 34 microM). Km values of the cloned enzyme in the absence of AdoMet are
      3.1 and 1.1 mM for serine and homocysteine, respectively. They are virtually
      identical to those from human hepatic CBS. A Soret absorbance band (lambda max =
      428 nm) which shifted to 448 nm after reduction with sodium dithionite revealed
      the presence of heme in the enzyme. Expression of the fusion protein in E. coli
      with subsequent purification represents the first time this enzyme has been
      isolated in sufficient quantities for biophysical and biochemical investigation.

PMID- 7827503
TI  - Expression in Escherichia coli: production and purification of both subunits of
      the human general transcription factor TFIIE.
AB  - Both subunits of the human class II transcription factor TFIIE (rTFIIE alpha and
      rTFIIE beta) have been overexpressed in Escherichia coli at 26 degrees C using a
      T7 RNA polymerase expression system and further purified to apparent homogeneity.
      As in this system rTFIIE alpha was poorly expressed and copurified with a
      truncated form, we expressed rTFIIE alpha as a fusion protein. These
      overexpressed subunits of TFIIE are similar to the endogenous subunits according
      to the following criteria: molecular weight, microsequencing, and transcription
      activity.

PMID- 7827504
TI  - Purification of recombinant human transcription factor IIB by immunoaffinity
      chromatography.
AB  - The human RNA polymerase II transcription factor IIB (TFIIB) was purified from a
      bacterial expression system by immunoaffinity chromatography. Mouse monoclonal
      antibodies (MAbs) were prepared that react with TFIIB. A modified enzyme-linked
      immunosorbent assay was used to screen for MAbs that release the antigen in the
      presence of a low molecular weight polyhydroxylated compound and a nonchaotropic
      salt (polyol-responsive MAbs). One polyol-responsive MAb (designated IIB8) was
      purified by chromatography on protein A and conjugated to cyanogen bromide
      activated Sepharose 4B. Escherichia coli strain BL21 (DE3) containing the pLysS
      plasmid was transformed with the human TFIIB gene contained in the pET11a vector
      (phIIB). After induction with IPTG, the cells were harvested and lysed. The
      lysate was treated with 0.5% polyethyleneimine and centrifuged. The supernatant
      fluid was applied to the IIB8-Sepharose. After extensive washing, the TFIIB was
      eluted with Tris-EDTA buffer containing 0.75 M ammonium sulfate and 40% propylene
      glycol. The purified TFIIB was active when added back to TFIIB-depleted HeLa
      nuclear extract and when used in the IgH minimal promoter system. This method
      will be useful for the rapid purification of TFIIB mutants and for the
      purification of large amounts of highly purified TFIIB for biochemical studies.
      In addition, this procedure establishes the general applicability of the use of
      polyol-responsive MAbs for the rapid, gentle purification of labile proteins.

PMID- 7827505
TI  - Importance of codon preference for production of human RAP74 and reconstitution
      of the RAP30/74 complex.
AB  - RAP30 and RAP74 are subunits of RAP30/74 (TFIIF, beta gamma), a general
      initiation and elongation factor for transcription by RNA polymerase II. Methods
      were previously published for production of human RAP30 and RAP74 in bacterial
      cells, using a bacteriophage T7 promoter expression system. The vectors described
      for production of RAP74 were not very efficient and produced significant
      quantities of RAP74 amino terminal fragments. To improve these vectors, a segment
      of the human RAP74 cDNA was recoded using a preferred set of codons for
      translation in Escherichia coli. Recoding dramatically improved protein
      production and suppressed production of amino-terminal fragments. Improved
      vectors are reported that produce RAP74 with an LEHHHHHH carboxy-terminal
      extension (RAP74-H6), for purification on a Ni(2+)-affinity column, and also with
      the native carboxy terminus (RAP74). Methods for purification of RAP74-H6 and
      RAP74 are reported. Using these improved vectors, approximately 30 mg of soluble
      and active RAP74-H6 or RAP74 can be produced and purified from 1 liter of E. coli
      culture, representing a 10-fold improvement in protein production. Methods have
      also been developed for reconstitution of native RAP30/74 complex using
      recombinant proteins. This complex has indistinguishable activity from human
      RAP30/74 for accurate transcription in vitro.

PMID- 7827506
TI  - Heterologous expression of the cytotoxin restriction in Aspergillus nidulans and
      Aspergillus niger.
AB  - The cDNA clone of restrictocin was placed under the control of the glucoamylase
      promoter from Aspergillus awamori and was transformed into Aspergillus nidulans
      and Aspergillus niger. Site-specific changes were introduced into cDNA constructs
      and these were transformed into A. nidulans. The secretion signal sequence was
      deleted from one form of the gene and three mutations introduced single amino
      acid substitutions into the protein. Culture conditions were optimized for
      maximum expression levels of restrictocin. The activities of the expressed
      proteins were characterized with an in vitro rabbit reticulocyte assay. Protein
      synthesis in this assay was inhibited 50% by 2.5 ng/ml wild-type restrictocin,
      3.5 ng/ml E95G, 30 ng/ml E95C, and 600 ng/ml H136L. Toxic effects of restrictocin
      were observed in the A. nidulans expression system with reduced levels of
      cellular protein and messenger RNA upon induction of restrictocin expression as
      well as the formation of the alpha-fragment product of ribosomal RNA cleavage.
      Toxic effects were most highly pronounced in strains expressing restrictocin
      without the signal sequence, less so in strains expressing native restrictocin,
      and absent in strains expressing H136L restrictocin.

PMID- 7827507
TI  - High-level expression of biologically active, soluble forms of ICAM-1 in a novel
      mammalian-cell expression system.
AB  - LFA-1/ICAM-1 interaction is important in facilitating a number of cellular events
      including antigen-specific T-cell activation and leukocyte transendothelial
      migration. We are interested in defining residues and contact sites that mediate
      ICAM-1 interaction with the integrin receptor, LFA-1. To provide sufficient
      material to facilitate study of the interaction of this ligand-receptor pair, we
      have developed a new high-level mammalian-cell expression system based on the use
      of the herpes simplex virus (HSV) VP16 transactivator and the HSV IE175 promoter
      to direct expression of foreign genes in BHK cells. In this system, the gene of
      interest is expressed as a fusion protein with a carboxyl terminal decapeptide
      tail to aid in identification, quantitation, and affinity purification of
      recombinant protein. This system allowed rapid generation of cell lines producing
      high levels of levels of soluble proteins corresponding to the full-length
      extracellular (sICAM453) and the amino terminal two immunoglobulin domains
      (sICAM185) of ICAM-1. Both sICAM453 and sICAM185 were biologically active and
      were purified in a single step from conditioned media by antibody affinity
      chromatography.

PMID- 7827508
TI  - In vivo biotinylated recombinant antibodies: construction, characterization, and
      application of a bifunctional Fab-BCCP fusion protein produced in Escherichia
      coli.
AB  - We describe a novel vector system suitable for the efficient preparation of in
      vivo biotinylated antibody Fab fragments in Escherichia coli. The previously
      described pGE20 vector used for the functional expression of truncated heavy (Fd)
      and light (L) chains of Fab into the bacterial culture medium was modified by
      inserting the C-terminal 101-amino-acid polypeptide of the biotin carboxyl
      carrier protein subunit of E. coli acetyl-CoA carboxylase (BCCP*). The secreted
      Fd-BCCP* fusion and L chain proteins were found to be disulfide linked and Fab
      BCCP* complexes of an IgG1 antibody (Mab4) to human tumor necrosis factor alpha
      (TNF) were shown to retain both antigen and streptavidin-binding activities. The
      capacity of the Fab4 linked to BCCP* to bind TNF was identical to that observed
      with unmodified Fab4. Up to 15% of the expressed hybrids were able to interact
      with streptavidin when exogeneous d-biotin was added into the bacterial culture
      medium. The Fab4-BCCP* molecules were found to be more efficient than Fab4 linked
      to an engineered streptavidin-affinity tag for the detection of antigen on solid
      phase. In addition, we show here that the bacterially expressed Fab4-BCCP*
      complexes, adsorbed to streptavidin-agarose beads, can be used for the one-step
      purification of recombinant TNF by immunoaffinity chromatography.

PMID- 7827509
TI  - Recombinant cholera toxin B subunit in Escherichia coli: high-level secretion,
      purification, and characterization.
AB  - The gene coding for cholera toxin subunit B (CT-B) was fused to a modified ompA
      signal sequence and subsequently cloned into a high expression vector based on
      the regulatory signals of the arabinose operon of Salmonella typhimurium. Upon
      induction of gene expression in Escherichia coli, a product of the expected size
      for CT-B monomer was detected at a level of approximately 60% of total
      periplasmic protein. At pilot scale, batch cultivation in a 20-liter bioreactor
      allowed a production level of 1 g/liter of recombinant CT-B (rCT-B), the majority
      of which was released into the culture medium. The latter phenomenon was
      dependent on the medium selected for cultivation. A simple and inexpensive
      purification scheme was developed which enabled the recovery of 81% of rCT-B from
      the culture supernatant. Comparing amino acid composition, amino-terminal
      sequence, mass spectrum, pentamerisation, and GM1-binding, rCT-B is
      indistinguishable from natural CT-B produced by Vibrio cholerae. This rCT-B
      overproducing E. coli strain represents an interesting alternative to
      overexpressing systems developed in V. cholerae.

PMID- 7827510
TI  - [In memory of Doctor Mazengo Bwanga, Zaire physician who died of exhaustion
      following the cholera epidemic of Shaba (Zaire) in 1981].

PMID- 7827511
TI  - [Serological markers for hepatitis A, B and C in Madagascar. First investigation
      in a rural area].
AB  - The first serological survey of hepatitis A, B and C virus infection was carried
      out in Madagascar during 1993 in two rural villages (653 sera) of the middle
      west. This study shows a high frequency of positivity of hepatitis A virus
      markers (94.9%). Hepatitis A is acquired in early childhood. The data show the
      high frequency of positivity of hepatitis B (HBV) markers: in the two villages
      72.5% and 89.8% have one marker, and seroprevalence of HBs antigene is 18.9% and
      30.5%. Hepatitis B also is acquired in early childhood. The data show that not
      only hepatitis A and B but also hepatitis C is highly prevalent (2.2% and 5.8%).
      There was an increase in HCV antibody prevalence with age.

PMID- 7827512
TI  - [Seroepidemiological survey of El Tor cholera in an endemic region of Algeria].
AB  - Between the 26th of April and the 8th of july 1987 a seroepidemiological survey
      was conducted in the district of Chlef located in an endemic cholera area of
      Algeria. The purpose of this work was to evaluate the seroprevalence of
      vibriocidal antibodies and to study some epidemiological characteristics of
      cholera. This survey concerns the representative samples of patients and
      asymptomatic carriers such as they were declared during the epidemic periods of
      1982 and 1986 and a sample of contacts of these latter. A bacteriology of stools
      practised on all the subjects did not reveal a carrying of vibrios. The
      seroprevalence was 37.6% and it concerned all ages. It was linked meaningfully to
      the age category and not to the sex. This seroprevalence was not significantly
      different between the cases, the carriers and the contacts. Thus this study
      reveals that Algeria has a seroprevalence rate less important than others
      countries.

PMID- 7827513
TI  - [Rhinopharyngeal carriage of Neisseria meningitidis serogroup C in the
      collectivity around the patients of Mali. Apropos of 1,033 subjects sampled].
AB  - This study showed that the carriage rate is nul or low in collectivity not in
      close contact, but high in collectivity in close contact (schools, particularly
      coranic schools). In this later case, the duration of the carriage may reach
      several weeks (2 to 6 in our study) at variable rates (3.7 to 9.6%; 12.5 to
      62.5%; 14.3 to 42.9% according to the coranic school visited). For the strains of
      N. meningitidis serogroup C isolated, the rate of resistance to sulfamides and
      cotrimoxazole is 86.8%. These results explain why during epidemics, it is
      necessary to close schools and avoid to use for the chemoprophylaxis, sulfamids
      and their associations because of resistance.

PMID- 7827514
TI  - [Development of primary resistance of tuberculosis bacilli in Mali between 1980
      and 1990].
AB  - The survey of the primary resistances of tuberculosis bacilli to drugs is not
      only important epidemiologically speaking, but also for its use as a guideline to
      defining programs, to assessing the quality and the practical development of
      chemotherapy in a country, to measuring the propensity of the resisting
      tuberculosis bacilli to infect a given population within some time and to taking
      the necessary remedial measures. The object of this study has been to compare the
      rate of initial drugs' resistances of tuberculosis bacilli in Mali between 1980
      1982 and 1989-1990. The results, which show a fall in the primary resistances due
      to drugs and to the combination of antibiotics as well, are being discussed while
      taking account various factors related to the organization.

PMID- 7827515
TI  - [Transmission of malaria in villages far away or situated on the border of a
      mangrove in Senegal].
AB  - During 23 months period, entomological surveys were carried out in three villages
      of a mangrove area and two others far of the mangrove in the south part of
      Senegal. An. gambiae s.s was the main malaria vector and the sampling of its
      population was done by human baits catch. The An. gambiae density was important
      in the rainy season and the malaria transmission occurred from July to November;
      the inoculation rate rose from 0 to 123 infected bites per man. Marked yearly and
      local variations of the transmission intensity were observed. The transmission
      intensity was higher in the villages far of the mangrove than in those near. The
      variations of the transmission intensity were related to the larval breeding
      sites and to the longevity of the An. gambiae females.

PMID- 7827516
TI  - [Distribution of intermediate mollusc hosts in human schistosomiasis in the
      Office of Niger (Mali).II. Role of different habitats in the transmission].
AB  - To determine the role of habitats in the schistosomiasis transmission all the
      year, a study on snail hosts distribution was carried out within various parts in
      the irrigated system of the "Office du Niger". Bulinus truncatus and Biomphalaria
      pfeifferi were the only snail hosts recorded. Densities were low and 85% (46/54)
      of breeding sites contained less than 50 snails collected per man/hour. Primary
      and secondary canals play the most important role in disease transmission because
      of the stability of these habitats, the pollution of human water contact by
      remnants of food and wastes which favourised the snail growth and infestation.
      Prevalences were 23.3% (46/197) in Bulinus truncatus and 2.5% (6/243) in
      Biomphalaria pfeifferi. The cercariae shedding was permanent, but the infection
      varied significantly according to the snail species, the period and to the area.

PMID- 7827517
TI  - [Buruli's ulcer, a pathology little known in Benin. Apropos of 227 cases].
AB  - Cutaneous Mycobacterium infection is an endemic disease in Mono, Oueme and Zou
      districts in the south of Benin, where it seems rarely known. The authors are
      reporting the results of a clinical, bacteriological, epidemiological and
      therapeutical study about 227 patients. Children are the principal targets of
      this disease. Ulceration are often seen in a critical step (3 or 4) and acid-fast
      bacilli have been found from 189 of 227 patients tested by bacilloscopy (smear
      microscopy). Medical treatments (antituberculosis and antileprosis drugs) are
      still disappointing. Also when necessary, surgery is done (broad excision, skin
      transplant afterwards) with promising results. However, complications like
      deformities and flexion contractors can persist after surgical treatment. In the
      south Benin, Buruli's ulcers are one of the major public health problems.

PMID- 7827518
TI  - [Dermatological aspects of AIDS in western Africa. Apropos of 140 cases].
AB  - This clinical survey, carried out during a 3 years period in the Dermatological
      Department of Bouake Hospital (Ivory Coast) analyses the skin and mucous
      membranes troubles caused by AIDS among adults. It is the first of that kind in
      Western Africa. 140 patients were concerned, showing carious dermatological
      troubles, 25 of them were counted. Few tropical skin diseases have their clinical
      picture altered by immunodeficiency. However, the Buruli ulcer may be described,
      which has in this condition a particularly development. We have underlined the
      particularities of some ubiquitous diseases, either because they appear on black
      skin (seborrheic dermatitis, Kaposi's sarcoma, prurigo, woolly hair syndrome,
      ichtyosis) or because they were neglected, or because they take an extensive form
      (chronic herpes, profuse condyloma). At the end of the survey, we are proposing a
      classification of the dermatological troubles, according to their features which
      might suggest AIDS. On this account, erythroderma, scattered forms of
      Mycobacterium ulcerans infection, and noma, find a place among the troubles
      suggesting adult AIDS in sub-saharian Africa.

PMID- 7827519
TI  - [First clinical and serological description of leptospirosis in Gabon].
AB  - We report the first case of leptospirosis describe in Gabon. Several
      environmental factors could favour the transmission of the disease in that
      country.

PMID- 7827520
TI  - [A case of subcutaneous dirofilaria (Nochtiella) repens with microfilaremia
      originating in Corsica].

PMID- 7827521
TI  - [Epilepsy, intracranial hypertension, confusional syndrome and cutaneous
      cysticercosis. Apropos of 1 case observed in a hospital in Benin].
AB  - We report the first case of diffused cysticercosis combined with epilepsy,
      myositis and confusional syndrome in Benin. In the absence of tomodensitometric
      exploration, the patient was treated with success by praziquantel and
      corticosteroids. This implies the existence of a human focus of cysticercosis in
      Benin.

PMID- 7827522
TI  - [Plasmodium vivax malaria seizure more than 5 years after a stay in Meknes
      (Morocco)].
AB  - The authors report a case of Plasmodium vivax malaria which happened more than
      five years after a stay of the patient in Morocco. The late appearance of
      parasite blood forms and especially gametocytes, as observed in this case, could
      explain, at least partially, the awakening of apparently extinguished foci and
      the renewal of the transmission of the epidemic, mediated by the presence of
      Anopheles. This phenomenon certainly contributed to the failure of malaria
      eradication campaigns in some countries with endemic P. vivax.

PMID- 7827523
TI  - [Seroprevalence of human immunodeficiency virus infection (HIV) in the central
      prison of Niamey (Niger)].
AB  - A study on seroprevalency among six hundred and sixty prisoners incarcerated at
      the central prison of Niamey (Niger) where toxicomania by intravenous injection
      is inexistant but homosexual probability does exist, the prison being a very
      closed circle, showed that 0.45% of the prisoners where carrying the anti body
      anti-HIV. This rate being about the same found in the general population 0.50%.

PMID- 7827524
TI  - [Former observations of urinary bilharziasis and wuchereriosis].
AB  - On the occasion of a book near completion on the great clinician Pierre Rayer
      (1793-1867), a pioneer of infectious pathology, are presented here two of his
      works concerning parasitic tropical pathology. The first (1838) signed by Rayer
      alone deals with an hematuria observed in patients from Mauritius. He
      distinguished several forms of the disease and described 15 observations which he
      compared to Egyptian hematuria of which the parasitic agent (Bilharzia (=
      Schistosoma) haematobium) will not be described before 1852 by Th. Bilharz. A
      very recent paper by Julvez (1992) confirms the persistence of this parasitic
      disease in Mauritius. The second paper published in 1850 with his disciple
      Casimir Davaine (1812-1882) concerns a case of elephantiasis of the Arabs
      (wuchereriosis) occurring in Guadeloupe (French West Indies). The authors
      describe carefully the anatomo-pathological features of the amputated hand and
      forearm of the patient. They could not be aware of the parasitic etiology of the
      disease which although suspected by J. Hendy (1784) will be demonstrated only
      during the second half of last century (Demarquay, 1863; Wucherer, 1866; Lewis,
      1870 and Bancroft 1876 who observed microfilariae and filariae of the Nematode
      presently named Wuchereria bancrofti in the blood and lymph of the patients). Its
      transmission by mosquitoes (Aedes, Culex) will be demonstrated by P. Manson
      (1878). These little-known observations are examples of clinical descriptions of
      tropical parasitic disease before the discovery of the parasites involved. As
      such they deserved to be recalled here.

PMID- 7827525
TI  - [Historical epidemiology of bancroftian filariasis in southwest islands of the
      Indian Ocean].
AB  - Bancroftian filariasis arose in the South-West Indian Ocean Islands with human
      settlements. During the XIXe century, most of the islands were infected but the
      prevalence and clinical features of the disease were different from an Island to
      an other. The vectors are Cx. quinquefasciatus, An. gambiae, An. arabiensis, An.
      funestus. Even if Culex are proven vectors most of the transmission is due to
      anophelines. The introduction of the parasite was followed by an explosion of the
      diseases with dramatic clinical features. But since the beginning of the century
      the disease retreats. Whatever this is due to malaria vector control and
      specifies chemoprophylaxis or is linked to the rise of life standard is still a
      subject of debate.

PMID- 7827526
TI  - Carrie Abbott. Interview by Ina May Gaskin.

PMID- 7827528
TI  - The information-poor level of public debate about health care reform in the
      United States.

PMID- 7827527
TI  - Parteras de Cuscatlan: training midwives in rural El Salvador.

PMID- 7827529
TI  - Leap of faith.

PMID- 7827530
TI  - Epidural epidemic.

PMID- 7827531
TI  - Clarebeth Loprinzi Kassel. Interview by Ina May Gaskin.

PMID- 7827532
TI  - Anne Rose: nurse practitioner at Hawaii's Waianae coast. Interview by Karna
      Bramble.

PMID- 7827533
TI  - Seeking legal authority to prescribe.

PMID- 7827534
TI  - Treating open-angle glaucoma.

PMID- 7827535
TI  - Moral dilemmas experienced by nurse practitioners.
AB  - This article details the moral dilemmas experienced by NPs in their primary care
      practices. From the practitioners' stories emerged strong personal and
      professional values that guided and shaped the resolutions to the dilemmas. The
      dilemmas themselves and the values of the NPs offer insight into the role of the
      nurse in advanced practice. Implications based on these findings for clinical
      practice and NP education are also discussed.

PMID- 7827536
TI  - Reshaping the nurse practitioner image through socialization.
AB  - The image of the NP is bound to the traditional image of nursing, often impeding
      progress toward autonomous nursing practice. Through socialization NPs can be
      empowered to reshape their image, enabling them to educate the public to identify
      NPs as autonomous providers of health care. This is necessary to enhance the NP's
      ability to function in the future health care arena.

PMID- 7827537
TI  - On being a mentor to nurse practitioner students: the preceptor-student
      relationship.
AB  - This article explores the identity of NPs as clinical practice preceptors and
      mentors for NP students, including the inherent conflict created for preceptors
      by these overlapping role expectations. Also examined is the nurse practitioner
      student relationship with phases of the relationship between student and
      preceptor/mentor presented. Issues related to student and preceptor role
      development and personal characteristics of both impacting on the relationship
      are identified. Implications for client health outcomes, educational programs,
      students, preceptors and nursing researchers are discussed.

PMID- 7827538
TI  - Autonomy: a professional issue of concern for nurse practitioners.
AB  - Autonomy has been a professional issue for nurses and for nurse practitioners
      (NPs). Health care reform will be critical to continuing and improving the
      autonomous roles of NPs. Without autonomy to practice their skills freely as
      primary health care providers, the roles of NPs will most likely be limited in
      any reformed health care system. Insights into the issue of autonomy for NPs are
      discussed.

PMID- 7827539
TI  - Maximizing your value and worth, or: "Gerta says you're great"!
AB  - Before applying for a position as an NP, there are some basic areas that need
      review to establish your worth and value as an NP. The areas this article
      discusses are philosophy of practice, advanced degrees, national certification,
      NP organizations, and negotiating for salary and benefits.

PMID- 7827540
TI  - Productivity versus quality of care: ethical implications for clinical practice
      during health care reform.
AB  - Nurse practitioners must be alert to the changes related to health care reform in
      which models of delivery are focused on production to contain costs. Productivity
      models require providers to see more patients in less time. Ethical concerns
      regarding access to care, cost containment, and quality of health care services
      have implications for how NPs spend their time. Caring is discussed as the link
      between issues of cost containment and quality of care.

PMID- 7827541
TI  - Health care reform: issues for nurse practitioners.
AB  - Nurse practitioners are in a unique position to make a significant impact on the
      provision of primary health care in the presence of health care reform. To insure
      proper positioning in a managed health care system, NPs must take action at the
      national, state, and local levels. Proactive suggestions for NPs in the work
      setting, in the community, and at the state and national levels are presented in
      this article.

PMID- 7827542
TI  - Twenty five years of vascular trauma in Northern Ireland.

PMID- 7827543
TI  - Swiss opt for compulsory health insurance.

PMID- 7827544
TI  - Egypt sees U turn on female circumcision.

PMID- 7827545
TI  - Meta-analysis of efficacy of quinine for treatment of nocturnal leg cramps in
      elderly people.
AB  - OBJECTIVE: To assess quantitatively the efficacy of quinine (as quinine sulphate)
      compared with placebo in the treatment of nocturnal leg cramps. DESIGN: A meta
      analysis of six randomised, double blind, crossover trials. SETTING: Randomised
      trials that were available as of April 1994. SUBJECTS: A total of 107 general
      ambulatory patients who suffered from regular nocturnal leg cramps from six
      clinical trials. RESULTS: Data from individual patients were used to calculate
      point estimates and 95% confidence intervals for each of the outcome measures
      reported by these studies. Treatment with quinine resulted in a significant
      reduction in the number of cramps for a four week period compared with placebo
      (8.83 fewer cramps; 95% confidence interval 4.16 to 13.49). Treatment with
      quinine reduced the number of nights with cramps by 27.4% (24.0% to 30.8%)
      compared with placebo. Treatment did not produce a significant change in the
      severity or duration of individual nocturnal leg cramps. Side effects were
      uncommon. CONCLUSIONS: The results indicate that quinine can prevent nocturnal
      leg cramps in general ambulatory populations. Given the possible serious side
      effects of treatment with quinine, the benefits and risks in patients taking this
      drug should be closely monitored.

PMID- 7827546
TI  - Weight in infancy and prevalence of coronary heart disease in adult life.
AB  - OBJECTIVE: To determine whether low birth weight and low weight at 1 year are
      followed by an increased prevalence of coronary heart disease in adult life.
      DESIGN: A follow up study of men born during 1920-30 whose birth weights and
      weights at 1 year were recorded. SETTING: Hertfordshire, England. SUBJECTS: 290
      men born and still living in East Hertfordshire. MAIN OUTCOME MEASURE: The
      prevalence of coronary heart disease, defined by the Rose/WHO chest pain
      questionnaire, standard electrocardiographic criteria, or history of coronary
      artery angioplasty or graft surgery. RESULTS: 42 (14%) men had coronary heart
      disease. Their mean birth weight, 7.9 lb (3600 g), was the same as that of the
      other men. Their mean weight at 1 year, 21.8 lb (9.9 kg), was 1 lb (454 g) lower
      (95% confidence interval 0.1 to 1.8, P = 0.02). Percentages of men with coronary
      heart disease fell from 27% in those who weighed 18 lb (8.2 kg) or less at 1 year
      to 9% in those who weighed more than 26 lb (11.8 kg) (P value for trend = 0.03).
      This trend occurred in both smokers and non-smokers and within each social class.
      CONCLUSION: These findings add to the evidence that coronary heart disease is
      "programmed" during early growth.

PMID- 7827547
TI  - Immunisation against chickenpox.

PMID- 7827548
TI  - Arterial versus capillary sampling for analysing blood gas pressures.

PMID- 7827549
TI  - Antiplatelet treatment in elderly people with transient ischaemic attacks or
      ischaemic strokes.

PMID- 7827550
TI  - Positive and negative factors in defensive medicine: a questionnaire study of
      general practitioners.
AB  - OBJECTIVES: (a) To investigate defensive medical practices among general
      practitioners; (b) to compare any such practices with general practitioners'
      understanding of certain aspects of the terms of service and medical negligence
      and practitioners' concerns about the risk of being sued or having a complaint
      lodged. DESIGN: Postal questionnaire survey. Each questionnaire was followed by a
      reminder. SUBJECTS: 500 systematically selected general practitioners on the
      membership list of the Medical Defence Union. MAIN OUTCOME MEASURES: Answers to
      questions on defensive medical practices, understanding of certain aspects of the
      terms of service and medical negligence, and concerns about the risk of being
      sued or having a complaint lodged. RESULTS: 300 general practitioners returned
      the questionnaire (response rate 60%). 294 (98%) claimed to have made some
      practice changes as a result of the possibility of a patient complaining. Of the
      defensive medical practices adopted, the most common (over half of doctors
      stating likely or very likely) seemed to be increased diagnostic testing,
      increased referrals, increased follow up, and more detailed patient explanations
      and note taking. Respondents practised defensive medicine as a possible
      consequence of concerns about the risks of being sued or having a complaint
      lodged. This association was particularly strong for negative defensive
      practices. Defensive medical practice did not correlate with any misunderstanding
      about the law of negligence or the general practitioners' terms of service.
      CONCLUSIONS: General practitioners are practising defensive medicine. Some
      defensive practices such as increased patient explanations or more detailed note
      taking are clearly beneficial. However, implementing the findings of the Wilson
      report may increase negative defensive medical practices.

PMID- 7827551
TI  - Antibiotics carried in general practitioners' emergency bags: four years on.

PMID- 7827552
TI  - Thrombolysis in patients with diabetes.

PMID- 7827553
TI  - Bone marrow transplantation.

PMID- 7827554
TI  - Should obstetricians see women with normal pregnancies? Obstetricians should be
      included in integrated team care.

PMID- 7827555
TI  - Should obstetricians see women with normal pregnancies? Obstetricians should
      focus on problems.

PMID- 7827556
TI  - ABC of breast diseases. Carcinoma in situ and patients at high risk of breast
      cancer.

PMID- 7827557
TI  - Bronchiolitis.

PMID- 7827558
TI  - A fundamental problem of consent.
AB  - A consultant anaesthetist gave a diclofenac suppository for postoperative pain to
      a patient having four teeth extracted under general anaesthesia in the dental
      surgery. He did not seek the patient's specific consent preoperatively for use of
      the suppository but told her afterwards what he had done. Charged before the
      professional conduct committee of the General Medical Council with failure to
      obtain informed consent and assault, the anaesthetist was found guilty of serious
      professional misconduct and admonished. This decision has far reaching
      implications and has caused great concern.

PMID- 7827559
TI  - Hypocalcaemic stridor and infantile nutritional rickets.

PMID- 7827560
TI  - Driving, glaucoma, and the law. Diabetic patients must also satisfy regulations.

PMID- 7827561
TI  - Driving, glaucoma, and the law. Regular checks on medical fitness to drive
      needed.

PMID- 7827562
TI  - Driving, glaucoma, and the law. Visual field required for safe driving wrongly
      defined.

PMID- 7827563
TI  - Childhood antecedents of schizophrenia. Difference in antecedents between sexes
      may not be genuine.

PMID- 7827564
TI  - Antibiotics for sore throats. Patient and doctor should reach decision together.

PMID- 7827565
TI  - Side effects of dental materials.

PMID- 7827566
TI  - Antibiotics for sore throats. Potential of antigen detection tests.

PMID- 7827567
TI  - Should doctors charge doctors for medical services? Doctors should continue to
      choose NHS care.

PMID- 7827568
TI  - Should doctors charge doctors for medical services? Tradition of not charging
      should remain.

PMID- 7827569
TI  - Future of purchasing. Health authorities will have little power to implement
      strategies.

PMID- 7827570
TI  - Emergency care in general practice.

PMID- 7827571
TI  - Coronary artery disease in women.

PMID- 7827572
TI  - Future of purchasing. Contracting is a recipe for inefficiency.

PMID- 7827573
TI  - Agism and provision of thrombolysis.

PMID- 7827574
TI  - Secondary prophylaxis after myocardial infarction.

PMID- 7827575
TI  - Smoking in China.

PMID- 7827576
TI  - Vaccination against hepatitis A for travellers. Will alter the dynamics of
      transmission in Britain.

PMID- 7827577
TI  - Vaccination against hepatitis A for travellers. All relevant costs and
      consequences should be measured.

PMID- 7827578
TI  - Myths in medicine. Surveillance-containment is key to eradication of smallpox.

PMID- 7827579
TI  - Word of warning to junior ophthalmologists.

PMID- 7827580
TI  - Cot deaths.

PMID- 7827581
TI  - Prostate cancer mortality in the United States by cohort year of birth, 1865
      1940.
AB  - Prostate cancer is the second leading cause of cancer death among United States
      men, with rates among blacks twice those among whites. Over time, mortality has
      increased among nonwhites but has changed little among whites. Earlier reports
      have predicted that the rise among nonwhites would diminish because it appeared
      that those born in the late 1800s were at highest risk. Based on 1950-1989 United
      States mortality data and populations at risk estimated using census data, we
      assessed prostate cancer mortality trends over time in white, nonwhite, and black
      men. From 1950-1954 to 1985-1989, age-adjusted prostate cancer mortality rates
      increased slightly for whites (9%) but substantially for nonwhites (67%). Among
      whites, rates increased over time in men over age 80 years but remained constant
      for younger men. Among nonwhites, rates increased steeply in those above age 74
      years and slightly in the age group 65-74 years but declined in those under age
      65 years, with the rate of decrease much more rapid in those under 55. The
      predicted reduction in risk among nonwhite men born since 1900, reported in an
      earlier study based on the mortality pattern through 1970, has not occurred
      because rates continued to increase among older nonwhites. In summary, prostate
      cancer mortality rates are rising among older men and decreasing in nonwhite
      young men. While improved detection of the cancer may partly account for the
      trend, analytical studies are needed to investigate the reasons for the increase
      in prostate cancer mortality in older men, the decrease in nonwhite young men,
      and the increasing excess risk among blacks.

PMID- 7827582
TI  - Patterns of mortality from major cancers in Europe.
AB  - All ages and truncated (35 to 64 years) mortality rates from all neoplasms and
      from cancers of the lung, stomach, intestines, and breast for the six calendar
      quinquennia from 1960-1964 to 1985-1989 were computed from official death
      certification data and population estimates obtained from the World Health
      Organization database for total Europe (excluding former Soviet Union) and for
      three broad European areas: (a) member countries of the European Economic
      Community for the last period of the study; (b) other Western European countries;
      and (c) Eastern European countries. In Europe, mortality rates for all neoplasms
      increased for men and decreased for women. The increase in men can be largely
      explained by the major tobacco-related lung cancer epidemic throughout Europe.
      Lung cancer mortality rates rose steeply in Eastern Europe, where the truncated
      rates reached the highest levels ever observed, and there is no evidence of a
      leveling off. Stomach cancer mortality decreased in all Europe for both sexes,
      although rates remained higher in Eastern Europe, while intestinal cancer rates
      tended to level off around the highest values in various areas of the continent.
      Breast cancer showed a moderate but steady increase. Overall, the most
      unfavorable trends were in Eastern Europe, due to major epidemics in tobacco
      related neoplasms and in other common cancers related to diet and other lifestyle
      habits.

PMID- 7827583
TI  - Cancer patterns and risk factors in the African population of southwestern
      Zimbabwe, 1963-1977.
AB  - The incidence of cancer and the importance of some selected risk factors in its
      etiology were estimated from the data collected in the cancer registry of
      Bulawayo, Zimbabwe, during the period 1963-1977. Cancer cases were interviewed
      with a standard questionnaire, and more than 71% of these were complete. In men,
      the most frequent cancer sites were liver, esophagus, and lung, while in women,
      cervical cancer was the dominant malignant tumor, followed by cancers of the
      liver, breast, and bladder. Risk factors of cancer cases were estimated by case
      control analysis in which other cancers (excluding tobacco-related cancers in men
      and hormone-related cancers in women) were considered as controls. In men,
      tobacco smoking was associated with increased risk of lung cancer (odds ratio
      OR2, 5.2) and esophagus cancer (OR, 5.6) in the highest consumption category (15
      g of tobacco per day) compared to nonsmokers. Copper (OR, 1.5), gold (OR, 1.5),
      and nickel (OR, 2.6) miners had an increased risk of lung cancer, but no increase
      was found among asbestos miners (OR, 0.7). There was no independent effect of
      alcohol consumption on the risk of esophagus cancer. The presence of
      schistosomiasis was associated with a significantly increased risk of bladder
      cancer (OR, 3.9). The risk of invasive cervical cancer increased with number of
      children--the estimated odds ratio was 1.8 in women with six or more births--but
      no consistent association was found for first intercourse. In postmenopausal
      women, the risk of breast cancer increased with age at first pregnancy (but not
      in the highly fertile) and decreased with high parity, if age at first pregnancy
      was 19 or more.

PMID- 7827584
TI  - Examination of the effect of nongenetic risk factors on the familial risk of
      breast cancer among relatives of postmenopausal breast cancer patients.
AB  - Relatives of postmenopausal breast cancer patients have a greater risk of breast
      cancer than do women with no family history of the disease. However, no study has
      previously examined the contribution of other breast cancer risk factors to risk
      in these relatives, thus precluding the ability to discern between shared
      environment or genes as the cause of familial aggregation. We conducted a nested
      case-control study of 251 index case families and 234 index control families.
      Incident breast cancer cases occurring in 1988-1989 and cancer-free controls were
      selected from a prospective cohort study. A pedigree development form was mailed
      to identify female relatives, who were then mailed a health history
      questionnaire. Index cases were significantly more likely than index controls to
      have at least one first-degree female relative with breast cancer [odds ratio =
      1.62; 95% confidence interval = 1.03-2.54] after controlling for the total number
      of first-degree female relatives. After excluding the index cases and controls,
      logistic regression models were used to predict the odds of breast cancer in
      sisters (n = 72 cases). Sisters of index cases had slightly, although not
      statistically significant, elevated risk of both early-onset (age < 50 years;
      odds ratio = 1.34; 95% confidence interval = 0.54-3.30) and late-onset (age > or
      = 50 years; odds ratio = 1.56; 95% confidence interval = 0.87-2.79) breast
      cancer. Adjustment for nongenetic risk factors increased the odds ratio to 1.41
      and 1.81, respectively. These data suggest that risk to sisters of postmenopausal
      breast cancer cases may be increased for both early- and late-onset breast cancer
      and this risk is apparently independent of measured risk factors.

PMID- 7827585
TI  - Alcohol, tobacco, diet, mate drinking, and esophageal cancer in Argentina.
AB  - To study the role of hot mate drinking, alcohol, tobacco, and diet in esophageal
      cancer, a case-control study including 131 cases and 262 hospital controls was
      carried out in La Plata, Argentina. In multivariate analyses, statistically
      significant increases in risk were detected for alcohol, tobacco, and some
      dietary factors but not for hot mate drinking. A strong dose-response
      relationship was observed with the amount of alcohol consumed daily but not with
      the number of cigarettes smoked. The odds ratio for those drinking more than 200
      ml of ethanol/day compared to nondrinkers was 5.7 (95% confidence interval, 2.2
      15.2). An increased risk was also observed for those eating barbecued meat more
      than once a week (odds ratio, 2.4; 95% confidence interval, 1.2-4.8) as compared
      to those eating it less than once a week, and a reduction in risk was associated
      with daily consumption of nonbarbecued beef as compared to those eating it less
      than daily. Concerning mate drinking, the only variable that showed an effect was
      the temperature at which mate is drunk. Those who reported drinking mate hot or
      very hot as compared to those drinking it warm had an increase in risk (odds
      ratio, 1.7; 95% confidence interval, 1.0-2.9). Our findings strengthen the
      evidence for an important role of alcohol and tobacco in esophageal
      carcinogenesis but do not provide strong support for a role of hot mate drinking.

PMID- 7827586
TI  - Coffee, tea, tobacco, and cancer of the large bowel.
AB  - The impact of tobacco use and coffee and tea intake on the risk of colorectal
      cancer is unclear. Previous research has suggested that coffee may be protective
      against these cancers, and investigation regarding tea or cigarette smoking has
      yielded inconsistent results. To clarify these issues, we evaluated coffee and
      tea intake and tobacco smoking as risk factors for cancer of the colon and rectum
      in a population-based case-control study from Stockholm, Sweden. Cases were
      ascertained from the regional cancer registry, and controls identified through
      population registers. Subjects completed a questionnaire requesting information
      regarding foods and beverages consumed, exercise, tobacco use, and personal
      characteristics. Logistic regression modelling was used to compute odds ratios. A
      total of 352 cases of colon cancer, 217 cases of rectal cancer, and 512 controls
      took part. High coffee intake was negatively associated with the risk of colon
      cancer: the odds ratio for those drinking 6 or more cups per day was 0.55 (95%
      confidence interval, 0.31-0.96) compared to those drinking one or fewer. There
      was no association with rectal cancer. For tea, the associations were the
      opposite: there was no association with colon cancer risk, but the odds ratio for
      rectal cancer was 0.56 (95% confidence interval, 0.34-0.90) for those drinking 2
      or more cups per day compared with those drinking none. Smokers of 11 or more
      cigarettes per day had a 20 to 30% reduction in the risk of colon and rectal
      cancer, but these findings were consistent with chance. There was no association
      of long-term cigarette smoking with risk.

PMID- 7827587
TI  - Increased plasma level of cholesterol-5 beta,6 beta-epoxide in endometrial cancer
      patients.
AB  - Plasma levels of alpha- and beta-isomers of cholesterol-5, 6-epoxides were
      quantitated in a pilot study of 9 women with endometrial cancer and 9 race- and
      age-matched control women by isotope dilution gas chromatography/mass
      spectrometry. Endometrial cancer cases had significantly higher cholesterol-5
      beta,6 beta-epoxide levels than the controls (P = 0.01). The mean plasma beta
      epoxide level was 0.71 +/- 0.46 ng/ml for the cases and 0.35 +/- 0.25 ng/ml for
      the controls. No significant differences were found between the plasma alpha
      epoxide levels of the cases and the controls. Plasma levels of various
      carotenoids, tocopherols, and ascorbic acid were also quantitated by high
      performance liquid chromatography. An inverse correlation was present between the
      plasma levels of cholesterol-5 beta,6 beta-epoxide and cis-lutein/zeaxanthin (P =
      0.01). These data suggest a possible role for cholesterol-5 beta,6 beta-epoxide
      as a biomarker of endometrial cancer risk. Further studies are warranted to
      investigate the possible association between the oxidation products of
      cholesterol and endometrial cancer and to determine the interactive role of
      antioxidants.

PMID- 7827588
TI  - Endometrial cancer risk in relation to serum lipids and lipoprotein levels.
AB  - Blood lipids are useful biochemical indicators for assessing the risk of a number
      of chronic diseases, particularly those associated with obesity. In a multicenter
      case-control study that included 256 cases and 185 controls less than 75 years
      old, we studied the risk of endometrial cancer in relation to serum cholesterol,
      low density lipoprotein cholesterol, high density lipoprotein cholesterol, and
      triglycerides. Contrary to expectation, blood lipids were, in general, lower
      among cases compared with controls. The effects of low blood lipids, specifically
      cholesterol and low density lipoprotein cholesterol, were limited to older women
      (> or = 55 years). Risk of the disease in this subgroup of 177 cases and 110
      controls was increased 3-4-fold among those with the lowest cholesterol or low
      density lipoprotein cholesterol values. For example, after adjustment for age,
      education, smoking status, obesity, and body fat distribution, the relative risks
      of endometrial cancer across decreasing quartiles of serum cholesterol were 1.0,
      2.5, 2.4, and 4.2 (P for trend < 0.01). We examined blood lipid levels by disease
      stage. The low lipid values of older cases did not appear to be a consequence of
      the disease. While we cannot rule out the possibility that hypocholesterolemia is
      a predisposing factor for endometrial cancer, there is no obvious biological
      explanation for the inverse association.

PMID- 7827589
TI  - Increased micronuclei in exfoliated bladder cells of individuals who chronically
      ingest arsenic-contaminated water in Nevada.
AB  - It is well established that inorganic arsenic is causally associated with lung
      cancer via inhalation and skin cancer via ingestion. Epidemiological evidence
      based on studies in Taiwan suggests that ingestion of inorganic arsenic may also
      cause other more fatal internal cancers, with the highest relative risks reported
      for bladder cancer. Here, we have used a biological marker of response, the
      micronucleus assay in exfoliated bladder cells, to evaluate the possible
      genotoxic effects of chronic arsenic ingestion on the bladder. The overall
      objective of this study was to compare the frequency of micronucleated cells in
      exfoliated bladder and buccal cells between a group of 18 individuals in Nevada
      who chronically ingested high levels of inorganic arsenic from their well water
      (average level, 1,312 micrograms/liter) and an individually matched control group
      with low exposure to arsenic (average level, 16 micrograms/liter). A 1.8-fold
      increase (90% confidence interval, 1.06-2.99) was observed in the weighted mean
      frequency of micronucleated bladder cells in the exposed group (2.79 per 1000
      cells) compared with the unexposed group (1.57 per 1000 cells). In addition, the
      frequency of micronucleated bladder cells was positively associated with the
      urinary concentration of inorganic arsenic plus its methylated metabolites
      (Spearman correlation = 0.33; P = 0.03). In contrast, there was no increase in
      micronucleated buccal cells associated with arsenic ingestion (frequency ratio =
      1.0; 90% confidence interval, 0.65-1.53). The results of this study provide
      evidence that chronic ingestion of high levels of inorganic arsenic in drinking
      water is associated with an increased frequency of micronucleated bladder cells.
      These findings are consistent with a genotoxic effect of arsenic on bladder
      cells, but a larger study is needed to confirm them.

PMID- 7827590
TI  - Long-term responses of women to indole-3-carbinol or a high fiber diet.
AB  - We test the hypothesis that the estrogen metabolite ratio 2-OH-estrone:estriol
      can be raised via dietary indole-3-carbinol (I3C) and that this higher ratio can
      be sustained over a 3-month test period. We also explore the possible role of
      pure fiber on estradiol metabolism. Using a randomized clinical trial with three
      arms, each containing 20 subjects, arm 1 received 400 mg/day of I3C daily for 3
      months, arm 2 received 20 g of alpha-cellulose daily for the same time period as
      a source of added fiber, and arm 3 received a placebo dose. Blood levels of a
      variety of biochemical parameters were measured. The urinary 2-OH-estrone:estriol
      estrogen metabolite ratio was measured monthly at the same time of the menstrual
      cycle. While no changes were observed in the control and alpha-cellulose-treated
      arms, a substantial mean increase in the ratio was observed in the I3C-treated
      arm at month 1; that increase was maintained over the 3-month time period. Three
      of the 20 subjects in this I3C-treated group differed from the others in that no
      significant change in the metabolite ratio was observed at any time point. The
      results suggest that I3C can serve to increase the 2-OH-estrone:estriol
      metabolite ratio in a sustained manner without detectable side effects and that
      some individuals may be resistant to such change.

PMID- 7827591
TI  - Reproducibility and variability of the rectal mucosal proliferation index using
      proliferating cell nuclear antigen immunohistochemistry.
AB  - Rectal mucosal proliferation has been shown to be increased in patients with
      neoplastic lesions of the large bowel and may serve as a marker of risk for
      colorectal malignancy. We conducted analyses to determine reliability and
      components of variability that might suggest optimal analysis strategies for
      studies of proliferation. Endoscopic pinch biopsies were obtained from 17 adult
      patients, labeled using proliferating cell nuclear antigen, scored using strict
      rules, and then rescored. Labeling index, defined as the proportion of labeled
      cells in a crypt, was calculated for each crypt, biopsy, subject, and group.
      There was excellent reproducibility. The technician was able to select previously
      scored crypts 95% of the time. The overall labeling index was identical on
      repeat. There was considerable variability in labeling index among crypts from a
      single biopsy and between biopsies of a single subject. Variance component
      estimates suggested that 20% of the variability of labeling index was due to
      subject, 30% due to the biopsy within a subject, and 50% due to crypts within a
      biopsy. There were substantial gains in statistical power by scoring two biopsies
      rather than one. There was less gain from further increases in biopsy number.
      There was little statistical advantage for counting more than 8 crypts/biopsy.
      Demonstrating a decrease of 25% in the mean labeling index with 90% power could
      require more than 100 subjects/group. We conclude that proliferating cell nuclear
      antigen is an extremely reproducible method to determine proliferation index.
      There is considerable variability among subjects, biopsies, and crypts.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7827592
TI  - A unique morphology of Epstein-Barr virus-related early gastric carcinoma.
AB  - Epstein-Barr virus (EBV) involvement in gastric cancer is demonstrated by uniform
      presence of viral RNA in carcinoma cells as detected by EBV-encoded small RNA in
      situ hybridization, monoclonal proliferation of EBV-infected carcinoma cells, and
      elevated antibodies. Our review of selected early gastric cancers found that 46
      of 49 EBV-positive lesions (94%) but only four of 97 EBV-negative lesions (4%)
      conformed to a unique morphology, in which carcinoma cells formed lace patterns
      of branching and/or anastomosing structures with lymphocytic infiltration in and
      around the carcinoma nests in the mucosa. We conclude that EBV-related gastric
      carcinoma has a distinct and characteristic morphology in the early stage of
      development, and this lace pattern is a biomarker of EBV involvement in early
      gastric cancer.

PMID- 7827593
TI  - Measuring smoking cessation: problems with recall in the 1990 California Tobacco
      Survey.
AB  - Measures of quitting activity are important both to evaluate public health
      interventions and to predict the likelihood of future quitting in the individual
      smoker. In population surveys, such measures are generally based on recall and
      thus may lack validity. In this article, we present the results of a 1-year
      quitting history of 8924 persons from a random-digit dialed population survey
      conducted in California in 1990. Respondents often forgot dates of quit attempts
      other than the most recent. Also, our results suggest that respondents may not
      recall short quit attempts at all, especially if they took place more than a few
      months before the interview. Thus, accurate population measures of relapse rates
      or quitting activity should rely on recall only for the last few months before
      the interview. Using data from quit attempts that took place within 4 months of
      the interview, actuarial analysis showed that 71.1% of attempts lasted at least 2
      days, 58.5% at least 3 days, but only 39.2% lasted a week or more; this rate
      dropped to 19.6% at 1 month and to 14.1% at 3 months. As a predictive measure, a
      quit attempt that lasted a week or longer in the last year appears less biased by
      recall than any attempt of a day or longer in the last year.

PMID- 7827594
TI  - The natural history of cervical intraepithelial neoplasia: an argument for
      intermediate endpoint biomarkers.
AB  - Cervical cancer is the second most common malignancy in women worldwide and
      remains a significant health problem for women, especially minority women in the
      United States. Despite morbid and costly treatment with whole pelvic
      radiotherapy, radical surgery, and chemotherapy, the overall survival remains
      40%. While the epidemiological risk factors are well known, little is known of
      the pathobiology of cervical carcinogenesis. Prevention of cervical cancer and
      its precursors is an important objective. New strategies, both clinical and
      laboratory based, are desperately needed. Cellular and molecular characteristics
      of the pathobiology of cervical cancer and its precursors need to be quantified,
      thereby providing insights into the multistep process of cervical carcinogenesis,
      identifying those precancerous lesions at high risk for progression to invasion,
      providing potential targets for intervention, and providing intermediate end
      point biomarkers for chemopreventive therapies. The premise for this strategy in
      cervical cancer prevention is that squamous cancers of the female genital tract
      have a well defined preinvasive stage, and that carcinogenesis is a multistep
      genetic process which involves increasing dysregulation of proliferation and
      differentiation as lesions progress from normal to human papillomavirus infected
      tissue to cervical intraepithelial neoplasia to cancer.

PMID- 7827595
TI  - Carcinogenicity of some biological agents.

PMID- 7827596
TI  - Heart transplantation: an Indian dimension.

PMID- 7827597
TI  - Management of febrile neutropenia.

PMID- 7827598
TI  - Colposcopy in women with a normal Papanicolaou smear.
AB  - BACKGROUND: Colposcopy is usually done when the Papanicolaou smear is abnormal so
      that the necessity for cone biopsy is reduced. However, there is often a strong
      clinical suspicion of cervical neoplasia even though the smear is normal and this
      problem of the false negative Papanicolaou smear has not, we feel, been
      adequately addressed. We, therefore, examined the usefulness of colposcopy in
      detecting cervical neoplasia in women in whom the Papanicolaou smear was normal.
      METHODS: A cross-sectional design was used which included 80 patients in whom
      cervical neoplasia was suspected and who had undergone colposcopy in one
      gynaecology unit at the Christian Medical College Hospital, Vellore. The
      Papanicolaou smear result of these patients was then related to their diagnosis
      on colposcopy. RESULTS: The Papanicolaou smears were normal in 56 patients and
      abnormal in 24. In the normal Papanicolaou smear group there were 18 women with
      grade I cervical intra-epithelial neoplasia and 3 with grade II lesions. In the
      abnormal smear group there were 8 women with grade I cervical intra-epithelial
      neoplasia, 9 with grade II cervical intra-epithelial neoplasia and 1 had
      microinvasive carcinoma. Patients with abnormal Papanicolaou smears had a
      relative risk of 7.8 (95% CI 2.4 to 25.8) of having a lesion more advanced than
      grade I cervical intra-epithelial neoplasia compared with those in whom cervical
      neoplasia was only suspected clinically. CONCLUSION: When the clinician suspects
      cervical neoplasia but the Papanicolaou smear is negative, colposcopy reveals at
      least grade II cervical intra-epithelial neoplasia in 5% of patients. Such
      patients, therefore, need to be followed up closely or else have a colposcopy and
      directed biopsy.

PMID- 7827599
TI  - Prevalence of hepatitis B virus infection in healthy persons in North India.
AB  - BACKGROUND: There is scant information on the main methods through which
      hepatitis B virus infection is transmitted in India. We, therefore, studied the
      prevalence of hepatitis B surface antigen and antibody to hepatitis B surface
      antigen in voluntary blood donors as well as in those healthy groups who have a
      high risk of contracting this infection. METHODS: The groups at risk studied
      included commercial sex workers (635), eunuchs (28), truck drivers (217),
      professional blood donors (1117) and health care workers (1313). In addition,
      20,435 voluntary blood donors were also studied. RESULTS: Hepatitis B surface
      antigen (and its antibody) was positive in 2.6% (14%) of voluntary blood donors,
      3.6% (19%) of commercial sex workers, 5% (16%) of truck drivers, 12% (9%) of
      professional donors, 1.4% (19%) of health care workers and none (18%) of the
      eunuchs. Except professional donors and truck drivers, none of these groups had a
      higher positivity than the normal population (2.6%). CONCLUSIONS: Our results
      indicate that in India the so-called high risk groups, other than truck drivers
      and professional blood donors, are unlikely to represent major sources of
      infection.

PMID- 7827600
TI  - The first successful heart transplant in India.

PMID- 7827601
TI  - Prevention of hepatitis B infection: the appropriate strategy for India.
AB  - Hepatitis B infection is a major global health problem with a high morbidity and
      mortality. With safe and effective vaccines available, it is now possible to
      prevent it. Many countries have started national hepatitis B control programmes
      but no attempt has been made to do this in our country. An analysis of the
      available data on the epidemiology of hepatitis B infection in India reveals that
      perinatal maternofoetal transmission accounts for only a minority of hepatitis B
      virus carriers in India. Therefore, a policy of screening pregnant mothers for
      the presence of hepatitis B surface antigen and selective immunization of babies
      born to those who are surface antigen positive will have very little effect on
      the hepatitis B carrier rate in our population. Universal immunization of all
      newborns will have a much greater impact, it will be logistically simpler and
      more cost-effective--the cost of preventing one hepatitis B carrier being nearly
      one-fourth of that with selective immunization. We recommend that hepatitis B
      vaccine should be included in our country's expanded programme of immunization.

PMID- 7827602
TI  - Does outcome of breast cancer depend on dose and dose intensity of adjuvant
      chemotherapy?

PMID- 7827603
TI  - Nicotine and ulcerative colitis.

PMID- 7827604
TI  - Nutritional assessment.

PMID- 7827605
TI  - Clinical agreement in quantitative measurements.
AB  - With advances in medical technology, simpler and safer methods for diagnosis and
      therapy are increasingly replacing the old ones and it has become important that
      these be correctly assessed. When a measurement by a new method is the same as
      that using the old method, one frequently encounters the problem of assessing the
      agreement. Evidence such as a correlation equal to 1 or equality of means is
      known to be inadequate. However, two recent approaches--limits of agreement and
      intraclass correlation coefficient--have gained acceptance but each has its own
      merits and demerits. To help investigators choose a procedure which is
      appropriate and to help them use it properly, we provide a description of these
      two approaches and discuss their advantages and disadvantages, both clinical and
      statistical, using a real example.

PMID- 7827606
TI  - AIDS, public health and the panic reaction (Part I)

PMID- 7827607
TI  - Caste and medicine in India.

PMID- 7827608
TI  - The bio-social dimensions of poverty, Tata Memorial Hospital, Bombay, 18 March
      1994.

PMID- 7827609
TI  - Practice in the promised land--international medical graduates.

PMID- 7827610
TI  - Cadaveric renal transplants--our experience with relatives.

PMID- 7827611
TI  - High-tech 'progress'.

PMID- 7827612
TI  - Mercury and aplastic anaemia.

PMID- 7827613
TI  - Worm infestations and strict vegetarians.

PMID- 7827614
TI  - Emergence of multidrug resistant Escherichia coli O157:H7 in India.

PMID- 7827615
TI  - Training in the United Kingdom.

PMID- 7827616
TI  - Is continuing medical education necessary?

PMID- 7827617
TI  - Cell specific expression of a vasopressin transgene in rats.
AB  - A transgene consisting of the rat vasopressin structural gene containing a
      reporter in exon III, flanked by 5 kb of upstream and 3 kb of downstream
      sequences, is expressed in vasopressinergic, but not oxytocinergic, magnocellular
      neurons of rats. Functionally appropriate physiological stimuli increase
      transgene expression in magnocellular neurons in an exaggerated fashion; the
      magnitude of the transgene response to osmotic challenge exceeds that of the
      endogenous gene by 10-15 fold. Magnocellular vasopressinergic neurons in the rat
      are now accessible to rational and precise genetic perturbation of function and
      regulation.

PMID- 7827618
TI  - Adrenal steroid receptors: interactions with brain neuropeptide systems in
      relation to nutrient intake and metabolism.
AB  - The glucocorticoid, corticosterone (CORT), is believed to have an important
      function in modulating nutrient ingestion and metabolism. Recent evidence
      described in this review suggests that the effects of this adrenal hormone are
      mediated through two steroid receptor subtypes, the type I mineralocorticoid
      receptor and the type II glucocorticoid receptor. These receptors, which have
      different affinities for CORT, respond to different levels of circulating
      hormone. They mediate distinct effects of the steroid, which can be distinguished
      by the specific nutrient ingested and by the particular period of the circadian
      cycle. Under normal physiological conditions, the type I receptor is tonically
      activated, either by low basal levels of circulating CORT (0.5-2 microgram %)
      normally available across the circadian cycle or possibly by the
      mineralocorticoid aldosterone. This type I activation is required for the
      maintenance of fat ingestion and fat deposition that occurs during most meals of
      the feeding cycle. In contrast, the type II receptor is phasically activated by
      moderate levels of CORT (2-10 micrograms %) normally reached during the circadian
      peak. Activation of this receptor is required for the natural surge in
      carbohydrate ingestion and metabolism that is essential at the onset of the
      active feeding cycle when the body's glycogen stores are at their nadir, and
      gluconeogenesis is needed to maintain blood glucose levels. This receptor is also
      activated during periods of increased energy requirements, such as, after
      exercise and food restriction, when CORT levels rise further (> 10 micrograms %)
      and when its catabolic effects on fat and protein stores predominate to provide
      additional substrates for glucose homeostasis. These functions of CORT on fat and
      carbohydrate balance are mediated, in part, by type I and type II receptors
      located within the hypothalamic paraventricular nucleus, which is known to have
      key functions in controlling nutrient intake and metabolism, as well as
      circulating CORT levels. Moreover, the type II receptors within this nucleus, in
      addition to the arcuate nucleus, may interact positively with the peptide,
      neuropeptide Y, and the catecholamine, norepinephrine, both of which act to
      enhance natural carbohydrate feeding and CORT release at the onset of the natural
      feeding cycle. Thus, under normal conditions, endogenous CORT has a primary
      function in controlling nutrient ingestion and metabolism over the natural
      circadian cycle, through the coordinated action of the type I and type II steroid
      receptor systems. Through this action, CORT has impact on total caloric intake
      and body weight gain over the long term.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7827619
TI  - Localization of pituitary adenylate cyclase-activating polypeptide (PACAP) in the
      hypothalamus-pituitary system in rats: light and electron microscopic
      immunocytochemical studies.
AB  - The localization of pituitary adenylate cyclase-activating polypeptide (PACAP) in
      the hypothalamus-pituitary system in rats was examined in light and electron
      microscopic immunocytochemistry using a specific antiserum to synthetic PACAP 1
      38 (R0831). In light microscopic study, intensely PACAP-immunostained perikarya
      were observed in the supraoptic and paraventricular magnocellular nucleus in the
      hypothalamus. In the median eminence, many immunoreactive nerve fibers were
      observed in the internal layer, but a few immunoreactive terminals were noticed
      in the external layer. In the pituitary gland, numerous immunoreactive nerve
      fibers were observed in the posterior lobe. In the intermediate lobe, moderately
      immunostained cells were observed, but in the anterior lobe no immunostained
      cells were noticed. In electron microscopic study, PACAP-immunoreactivity was
      examined by avidin-biotin peroxidase complex method. In the perikarya of the
      supraoptic and paraventricular magnocellular nucleus, DAB-reaction products were
      distributed diffusely in the cytoplasmic matrix, frequently attaching to the
      rough-surfaced endoplasmic reticulum. In the nerve terminals of the posterior
      lobe, reaction products were observed among the secretory granules, but sometimes
      upon them. In the cells of the intermediate lobe, reaction products were also
      distributed in the cytoplasmic matrix.

PMID- 7827620
TI  - Evidence for multiple forms of melatonin receptor-G-protein complexes by
      solubilization and gel electrophoresis.
AB  - The daily production of melatonin from the pineal gland influences circadian and
      seasonal behaviour and physiology. To further understand how melatonin may
      function, it is important to characterize the receptor and signal transduction
      systems. Using the detergent digitonin, we were able to solubilize the receptor
      from the ovine pars tuberalis (PT) membrane. The receptor was isolated as a
      complex associated with its heterotrimeric G-protein. In the solubilized state,
      pre-bound 125I-2-iodomelatonin was stable at 4 degrees C, but was displaceable by
      GTP gamma S. The receptor-G-protein complex could be separated by molecular mass
      using native polyacrylamide gel electrophoresis. We demonstrate that the receptor
      complex has a molecular mass of 525 kDa and differs from solubilized receptor
      complexes isolated from either the lizard brain, chicken brain or the ovine
      hippocampus. Furthermore the receptor complex isolated from the hippocampus had
      the lowest molecular mass of these tissues (365 kDa) and was found not to be
      sensitive to GTP gamma S. This may indicate the existence of a distinct non-G
      protein coupled form of the receptor.

PMID- 7827621
TI  - The effects of aging and hormonal manipulation on amyloid precursor protein
      APP695 mRNA expression in the rat hippocampus.
AB  - In the rat hippocampus, neuronal morphology and survival are profoundly affected
      by adrenal steroids, and synaptic plasticity can be modulated by the ovarian sex
      steroids estrogen and progesterone. beta-amyloid peptides, which accumulate in
      neuritic plaques and are derived from the amyloid precursor protein (APP), have
      been shown to be both trophic and toxic for hippocampal neurons. Of the various
      APP isoforms, APP695 is the predominant form found in rat brain and the APP695
      mRNA is abundantly expressed in the hippocampus. In order to investigate the
      hypothesis that APP may serve as a mediator of the steroid effects, we have
      monitored the hippocampal expression of APP695 mRNA by in situ hybridization,
      with aging and with steroid manipulation. In aged female rats we observed a
      decrease in the level of APP695 mRNA relative to young female rats, while no such
      age difference was evident in male rats. Physiological, surgical and
      pharmacological manipulation of glucocorticoids appeared to have no effect on
      APP695 mRNA levels in the hippocampus. Treatment of young, ovariectomized female
      rats with estrogen and progesterone, resulted in an increase in hippocampal
      APP695 expression compared to untreated, ovariectomized controls.

PMID- 7827622
TI  - Melatonin regulates the phosphorylation of CREB in ovine pars tuberalis.
AB  - This study investigated whether melatonin could modulate the phosphorylation of
      the calcium/cyclic AMP response-element binding-protein (CREB) within primary
      cell cultures of ovine pars tuberalis (oPT) and pars distalis (oPD). Gel shift
      assays confirmed the presence of nuclear factors able to alter the
      electrophoretic mobility of a 32P-labelled CRE oligonucleotide. Two shifted bands
      were observed probably due to monomer and dimer binding to the CRE. Each band was
      supershifted by antisera directed against both CREB and the phosphorylated form
      of CREB (P-CREB), consistent with a specific role of CREB proteins in
      transcriptional regulation. To study the physiological role of CREB, the nuclear
      immunoreactivity for P-CREB was followed in primary cultures of oPT given
      different pharmacological treatments. Cells stimulated with forskolin responded
      with a robust time- and dose-dependent increase in nuclear phospho-CREB
      immunoreactivity (P-CREB-ir), confirming that activation of this transcription
      factor occurred through the cyclic AMP-PKA pathway. Maximal stimulation was
      achieved within 15 min and persisted for up to 1 h. Treatment with melatonin
      alone did not alter basal P-CREB-ir levels, yet melatonin inhibited the forskolin
      induced increase in P-CREB-ir in a dose-dependent manner (IC50 of between 10(-10)
      M and 10(-8) M melatonin when tested against 1 microM forskolin). In contrast, in
      primary cultures of oPD, melatonin failed to block forskolin-stimulated increases
      in either the content of cyclic AMP or the intensity of nuclear P-CREB-ir,
      confirming that the action of melatonin upon P-CREB-ir is tissue specific. These
      results demonstrate that, consistent with its inhibitory effect on the activation
      of PKA within oPT, melatonin prevents or reverses the phosphorylation of CREB
      induced by activation of the cyclic AMP signal transduction pathway. Therefore
      melatonin has the potential to regulate gene expression in the oPT by acting upon
      the CREB transcription factor. However, this paper also shows that 12-O
      tetradecanoylphorbol-13-acetate (TPA) which activates PKC also leads to the
      phosphorylation of CREB in oPT cells, suggesting the potential involvement of
      other signal transduction pathways in the transcriptional regulation of these
      cells.

PMID- 7827623
TI  - Neuroactive steroids modulate GABAA receptors in peptidergic nerve terminals.
AB  - Neuroactive steroid modulation of GABAA receptors was investigated in the
      peptidergic nerve terminals of the posterior pituitary using patch clamp
      techniques. In common with GABAA receptors in cell bodies, the nerve terminal
      GABAA receptor was potentiated by the synthetic steroid alphaxalone and by
      physiological concentrations of the progesterone metabolite allopregnanolone.
      Both of these agents enhanced Cl- currents elicited by GABA. Estradiol-17 beta
      had a weak inhibitory effect on GABA responses of nerve terminals, but only at
      high concentrations. The potentiating action was manifest as an increase in the
      probability of channel opening, with no effect on the rate of desensitization of
      the GABAA receptor. Neuroactive steroids enhanced GABA-gated Cl- channel activity
      in cell-free membrane patches, thus demonstrating a membrane delimited response.
      These results indicated that with regard to allosteric modulation by neuroactive
      steroids, the nerve terminal GABAA receptor is similar to the GABAA receptors of
      nerve cell bodies and endocrine cells. Neuroactive steroids are thus capable of
      altering the chemosensitivity of nerve terminal membranes by enhancing GABA
      inhibition at this location. The neuroactive steroid sensitivity of nerve
      terminal GABAA receptors provides a pathway by which gonadal steroid derivatives
      could regulate peptide secretion from neurosecretory neurons. Such a pathway
      could participate in the coordination of neuropeptide secretion during complex
      neuroendocrine functions. With specific regard to the neurohypophysis,
      neuroactive steroid-induced changes in the sensitivity of nerve terminal GABAA
      receptors could play a role in the initiation of oxytocin secretion during the
      transition between pregnancy and parturition.

PMID- 7827624
TI  - Increased hypothalamic somatostatin expression in mice transgenic for bovine or
      human GH.
AB  - Acute studies of GH removal by hypophysectomy or GH replacement in adult rats
      have shown that GH has a positive influence on its hypothalamic inhibitory
      hormone somatostatin (SRIH). The present study was undertaken to assess the
      effect of lifelong exposure to elevated GH on the development and differentiation
      of SRIH-producing hypothalamic neurons, including comparison of differing GH
      levels and heterologous species of GH. Expression of somatostatin peptide and
      mRNA was evaluated using respective immunocytochemistry and in situ hybridization
      in brains of transgenic mice bearing constructs of either human (hGH) or bovine
      (bGH) linked to metallothionein (MT) promoter or bGH linked to
      phosphoenolpyruvate carboxykinase (PEPCK) promoter. Nontransgenic littermates
      served as controls. All transgenic constructs resulted in high levels of
      circulating heterologous GH and significantly elevated body weights. Both bGH
      levels and body weights were higher in PEPCK-bGH than in MT-bGH mice; mean
      weights were not different between MT-bGH and MT-hGH mice. Numbers of SRIH
      immunoreactive neurons in the hypophysiotropic periventricular nucleus (PeN) of
      transgenic mice showed a two-fold increase (P < 0.01) relative to control
      animals; the number of SRIH-positive cells in the medial basal hypothalamus (MBH)
      was comparable for transgenic and control mice. Total SRIH mRNA in situ
      hybridization intensity also showed a two-fold increase (P < 0.05) in the PeN of
      all transgenic mice compared with controls, and was not elevated in the MBH. The
      higher levels of GH produced in PEPCK-bGH transgenic mice led to greater weight
      gain, but not to greater SRIH expression than in other GH-transgenic mice,
      suggesting that the increased SRIH cell number and mRNA in the PeN of MT-GH
      transgenic mice may represent a plateau of maximal feedback stimulation. The
      results indicate that lifelong elevated heterologous GH in mice stimulates
      hypothalamic SRIH expression markedly. It is not known whether this mechanism is
      direct or indirect via a mediator of GH such as IGF, but the heterologous GH
      appears to be specific to these hypophysiotropic neurons.

PMID- 7827625
TI  - Effects of pituitary adenylate cyclase-activating polypeptide (PACAP) and
      vasoactive intestinal polypeptide (VIP) on prolactin, luteinizing hormone and
      growth hormone secretion in the ewe.
AB  - This study was undertaken to investigate the roles of PACAP and VIP in the
      control of pituitary hormone secretion in the ewe. The first experiment was
      designed to identify any direct effects at the level of the pituitary and was
      conducted during the luteal phase of a prostaglandin-synchronized oestrous cycle.
      PACAP (0.008, 0.04, 0.2 and 1.0 nmol/min) or VIP (0.06, 0.2, 0.6 and 1.8
      nmol/min) was infused into the carotid artery over a 10 min period. Blood samples
      were taken before and after the infusions so that plasma PRL, LH and GH
      concentrations could be measured. Blood pressure was also monitored to determine
      if the doses used were biologically active. In no case was an effect on hormone
      secretion observed. In contrast, the highest dose of each peptide induced an
      increase in heart rate to almost three-fold the resting value. Although both
      peptides are active in vivo, this result suggests that neither peptide has a
      direct effect on hormone release from the pituitary of prostaglandin-synchronized
      ewes. In a second experiment, we investigated whether the peptides had central
      effects on hormone secretion. Intracerebroventricular (ICV) injection of PACAP or
      VIP at the dose 10 nmol was tested in ovariectomized ewes. After injection, PACAP
      suppressed PRL and GH secretion so that plasma hormone concentrations from 1-3 h
      after injection were significantly different from the control (P < 0.05 for PRL,
      P < 0.01 for GH). In addition, PACAP significantly reduced mean LH concentration
      (P < 0.05) and LH pulse frequency (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7827626
TI  - The hypothalamic peptides, beta-endorphin, neuropeptide K and interleukin-1 beta,
      and the opiate morphine, enhance the excitatory amino acid-induced LH release
      under the influence of gonadal steroids.
AB  - Several hypothalamic neuropeptides and amino acids are known to inhibit or excite
      pituitary luteinizing hormone (LH) release, but the precise interplay between
      these 2 classes of signals in episodic LH discharge is not known. In this study,
      we have evaluated the interaction between neuropeptides shown previously to
      inhibit LH release in castrated rats and the excitatory amino acid agonist, N
      methyl-D-aspartate (NMDA), on LH release in intact male rats. Rats received a
      permanent intracerebroventricular (i.c.v.) cannula and 9-12 days later an
      intrajugular cannula for frequent blood sampling. The next day, rats received
      i.c.v. either saline (SAL, 3 microliters, controls) or a neuropeptide: the opioid
      beta-endorphin (beta-END; 2.9 nmol), the tachykinin neuropeptide K (NPK, 2.5
      nmol) or the cytokine interleukin-1 beta (IL-1 beta, 5.9 pmol) in SAL. The LH
      response to 2 consecutive i.v. injections of NMDA (5 mg/kg) at 30 min intervals
      was evaluated. In control rats, each NMDA injection evoked a significant release
      of LH at 10 min. Quite unexpectedly, the three peptides, instead of exerting an
      inhibitory effect, enhanced the LH response to NMDA. The peak plasma LH levels
      after each NMDA injection and the cumulative LH responses were significantly
      higher in peptide-treated than in control rats. This peculiar ability of the
      peptides that inhibit LH release in castrated rats, to potentiate the NMDA
      induced LH release in the presence of gonadal steroids was further validated in
      female rats treated with an opiate receptor agonist, morphine (MOR) which is also
      known to suppress LH release in ovariectomized rats.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7827627
TI  - In situ hybridization detection of TSH beta subunit gene expression in the serum
      free primary culture of the adult rat pituitary.
AB  - This study was designed to construct the primary culture system to detect the
      change in TSH beta subunit (TSH beta) gene expression in individual cells. Adult,
      male Wistar rats were sacrificed by transcardial perfusion of 0.25% trypsin
      solution under pentobarbital anesthesia (50 mg/kg body weight). Their anterior
      pituitaries were removed, dispersed and cultured for 1, 2, 3, or 6 days with or
      without 1 nM triiodothyronine (T3) under the serum-free condition. In some
      cultures, TRH was added to a final concentration of 1 microM on 6, 12 or 24 h
      before fixation. Then the culture media were removed to measure TSH
      concentration. Cells were fixed with paraformaldehyde and hybridized with 35S
      labeled RNA probe complementary to TSH beta mRNA. Emulsion autoradiography was
      subsequently performed. T3 treatment markedly suppressed relative cellular levels
      of TSH beta mRNA on 2, 3 and 6 days after the onset of culture (day 2, 3 and 6)
      and suppressed TSH secretion on day 3 and 6. TRH treatment increased TSH beta
      mRNA on 12 and 24 h after the treatment on day 2 and 3 but did not increase TSH
      beta mRNA on day 6. TSH concentration in the culture medium was increased by TRH
      treatment on 6, 12 and 24 h after the treatment on day 2, on 12 h and 24 h on day
      3, and 24 h on day 6. On day 2 and 3, although T3 treatment suppressed basal
      level of TSH beta mRNA, TRH-induced increase in TSH beta mRNA was not suppressed
      by T3 treatment. These results show that the thyroid hormone and TRH regulate TSH
      beta gene expression independently. Our culture system may provide a useful model
      to examine the action of individual substances on a specific subpopulation of the
      anterior pituitary cells.

PMID- 7827628
TI  - Distribution of estrogen receptor-immunoreactive cells in the brain of the
      rainbow trout (Oncorhynchus mykiss).
AB  - Using antibodies against the hormone binding domain of the trout estrogen
      receptor (ER), the distribution of ER-immunoreactive (ER-IR) cells was studied in
      the brain of maturing diploid and triploid female rainbow trout using a
      streptavidin-biotin-peroxidase method followed by a nickel-intensified
      diaminobenzidine reaction. This technique resulted in an excellent
      signal/background ratio allowing unambiguous identification of positive cells. In
      all animals, ER-IR cells were consistently located in three brain regions, the
      ventral telencephalon, the anterior ventral preoptic region, and the mediobasal
      hypothalamus. About 250 ER-IR cells were observed in the ventral and dorsal parts
      of the ventral telencephalon. In the anterior nucleus preopticus
      periventricularis, about 2400 ER-IR cells were observed surrounding the preoptic
      recess. In the posterior hypothalamus, approximately 2700 ER-IR cells were
      located in the anterior, posterior and inferior divisions of the nucleus
      lateralis tuberis and in the nucleus saccus vasculosus. In these regions cell
      nuclei exhibiting different densities of staining were observed and absolutely no
      labeling of cytoplasmic processes was detected. These results are in partial
      agreement with those obtained either after injection of tritiated-estradiol in
      other teleots species or in situ hybridization of ER mRNAs in trout. In
      particular, no immunoreactivity was observed in the thalamic region nor in the
      nucleus posterioris periventricularis. These data indicate that target cells for
      estradiol are essentially located in brain regions involved in the neuroendocrine
      control of pituitary functions and having direct connections with the hypophysis.

PMID- 7827629
TI  - Current open and closed kinetic chain concepts--clarifying or confusing?

PMID- 7827630
TI  - The effects of three modalities on delayed onset muscle soreness.
AB  - Delayed onset muscle soreness is a common problem that can interfere with
      rehabilitation as well as activities of daily living. The purpose of this study
      was to test the impact of therapeutic massage, upper body ergometry, or
      microcurrent electrical stimulation on muscle soreness and force deficits evident
      following a high-intensity eccentric exercise bout. Forty untrained, volunteer
      female subjects were randomly assigned to one of three treatment groups or to a
      control group. Exercise consisted of high-intensity eccentric contractions of the
      elbow flexors. Resistance was reduced as subjects fatigued, until they reached
      exhaustion. Soreness rating was determined using a visual analog scale. Force
      deficits were determined by measures of maximal voluntary isometric contraction
      at 90 degrees of elbow flexion and peak torque for elbow flexion at 60
      degrees/sec on a Cybex II isokinetic dynamometer. Maximal voluntary isometric
      contraction and peak torque were determined at the 0 hour (before exercise) and
      again at 24 and 48 hours postexercise. Treatments were applied immediately
      following exercise and again at 24 hours after exercise. The control group
      subjects rested following their exercise bout. Statistical analysis showed
      significant increases in soreness rating and significant decreases in force
      generated when the 0 hour was compared with 24- and 48-hour measures. Further
      analysis indicated no statistically significant differences between massage,
      microcurrent electrical stimulation, upper body ergometry, and control groups.

PMID- 7827631
TI  - Efficacy of prophylactic knee bracing in high school football players.
AB  - Controversy exists regarding the efficacy of prophylactic knee braces for
      football players. Starting players from eight high school football teams were
      studied, and the injury rate for players who wore prophylactic knee braces was
      compared with the injury rate of players who did not wear prophylactic braces. In
      the braced group, 23 knee injuries occurred in 21,640 exposures to contact during
      a 4-year period. In the nonbraced group, 26 knee injuries occurred in 19,484
      exposures during the same time period. No statistically significant difference in
      injury rates or severity of injuries between the two groups occurred. Considering
      these results and the expense of prophylactic knee bracing, the authors recommend
      that sports medicine practitioners do not advocate prophylactic knee bracing for
      high school football players.

PMID- 7827632
TI  - Anterior tibial translation during progressive loading of the ACL-deficient knee
      during weight-bearing and nonweight-bearing isometric exercise.
AB  - Many protocols for rehabilitating the knee following anterior cruciate ligament
      (ACL) injury or repair call for the use of both weight-bearing and nonweight
      bearing exercises. However, not much is known about the strain these exercises
      place on the passive restraining mechanisms. The purpose of this study was to
      examine the effect of progressive loading of the knee extensors on anterior
      tibial translation during weight-bearing and nonweight-bearing isometric
      exercise. Fourteen subjects diagnosed as ACL-deficient via arthroscopic surgery
      participated in the study. An arthrometer was used to measure anterior tibial
      translation during weight-bearing and nonweight-bearing exercises with the knee
      in 20 degrees of flexion and with a quadriceps load equivalent to 25, 50, 75, and
      100% of body weight. Hamstring muscle activations during all testing were
      monitored to eliminate the possibility of substantial cocontractions. During the
      weight-bearing exercise, anterior tibial translation was found to be
      significantly less than that measured during the Lachman's evaluation and the 50,
      75, and 100% nonweight-bearing exercises. For the nonweight-bearing exercises,
      anterior tibial translation was either equivalent to or greater than the
      Lachman's evaluation. During the weight-bearing exercises, anterior tibial
      translation was not different under the different loading conditions. During the
      nonweight-bearing exercises, anterior tibial translation progressively increased
      with increased loading. The results from this study imply that weight-bearing
      exercises minimize strain to the passive restraining structures whereas nonweight
      bearing exercises will strain these structures, and the magnitude of this strain
      appears to be proportional to the knee extensor moment.

PMID- 7827633
TI  - Muscle torque changes caused by inertial exercise training.
AB  - Inertial exercise is a unique form of muscle loading with minimal data available
      regarding its use or efficacy. The purpose of this study was to describe a
      standardized clinical training program for inertial exercise using the Impulse
      system and to experimentally examine the influence of an inertial training
      program on muscle torque performance. The biceps brachii of 40 healthy subjects
      were pretested and posttested on the Lido Active dynamometer at 60 and 120
      degrees/sec using the continuous passive motion mode. Subjects were randomly
      assigned to a control or training group. The training group exercised only the
      nondominant arm three times per week for 5 weeks on the Impulse system.
      Statistical analysis of peak torque measures between pretests and posttests of
      muscle torque was performed using a repeated measures analysis of variance design
      of one between-group (control vs. trained group) and three-within group (speed,
      arm, and movement; eccentric vs. concentric) factors. Posttraining peak torque
      measures for both the concentric and eccentric modes of exercise at 60
      degrees/sec and for the eccentric mode at 120 degrees/sec were statistically
      significant at the p < .05 level. Complaints of muscle fatigue occurred during
      early training sessions, with no injuries and only minimal soreness reported.
      Inertial training appears to be an effective form of clinical muscular training
      that is measurable by muscle torque assessment.

PMID- 7827634
TI  - Lumbar traction: a review of the literature.
AB  - Lumbar traction is commonly used to treat patients with back pain. Typically,
      clinicians rely on expert opinion in making decisions about when and how to
      implement lumbar traction. The purpose of this paper was to review current
      knowledge of lumbar traction and to identify what, if any, empirical evidence
      supports the expert opinions. This review found that whereas the mechanical
      effects of lumbar traction are well substantiated, the results of studies
      examining clinical effectiveness are conflicting. The failure to conclusively
      demonstrate the clinical benefit of lumbar traction may be related to the varied
      diagnostic categories and treatment techniques employed in the studies. Of the 10
      types of lumbar traction described in the literature, static and intermittent
      mechanical traction are the two most commonly used. Indications,
      contraindications, and treatment techniques for these two types of traction are
      discussed. Based on the findings of this review, further study is needed to
      determine optimal treatment duration, frequency, and mode of administering lumbar
      traction. Also, classification systems to identify patients most likely to
      benefit from traction need to be developed and validated.

PMID- 7827635
TI  - [Hormonal replacement therapy after breast cancer].

PMID- 7827636
TI  - [Ovulation induction apart from in vitro fertilization in practice: value of the
      combination of intra-uterine insemination, ovulation induction, pregnancy after
      stimulation].

PMID- 7827637
TI  - [Color Doppler in gynecology].

PMID- 7827638
TI  - [The cyclic administration of nomegestrol acetate does not alter the vasodilating
      effects of estradiol on the uterine artery].
AB  - Uterine artery blood flow was analyzed in 8 menopausal women receiving hormonal
      replacement therapy consisting of transdermal E2 (0.05 mg/24 h) administered
      without interruption for 12 weeks in combination with a cyclical supply of
      Nomegestrol acetate (5 mg/24 h) for the last 13 days of each four week treatment
      cycle. Uterine artery flow was analyzed using transvaginal pulsed Doppler making
      semi quantitative measurements of Doppler flow waves by calculation of the
      pulsatility index (PI). Before treatment (baseline) uterine artery PI was
      elevated at 3.7 +/- 0.7 (mean +/- SD) and decreased significantly under the
      influence of E2 to reach 1.9 +/- 0.8 after 2 weeks of treatment. This effect of
      E2 was not altered by the cyclical addition of Nomegestrol acetate. On the 3rd
      month of treatment, uterine artery PI values were lower than seen during the
      first month and no difference was observed between measurements made while
      receiving E2 (week 10) or E2 and Nomegestrol acetate (week 12). These data
      indicate that cyclical administration of the progestin Nomegestrol acetate does
      not interfere with the vascular effects of E2 lowering the uterine artery PI a
      reflector of the impedance to flow.

PMID- 7827639
TI  - [Cervical pathology and immunodepression].
AB  - The Human Papilloma Virus is often involved in the pathogenesis of cervical
      lesions. A local or systemic immunodeficiency allows neoplasia outbreaks. We do
      not know if immunodepression only allows the virus to persist, or if the HPV
      induces a local immunodeficiency. Large warts are often associated with
      pregnancy, but cervical cancers are not increased in pregnant women. Induced
      immunodeficiency (among transplanted patients), or AIDS increase the rate of CIN
      and cervical cancers. The more serious the immunodeficiency is, the more
      multifocal and recurrent the lesions are. We have to look for an immunodepression
      and for AIDS when we observe multifocal or recurrent lesions of the cervix,
      specially when the lesions do not regress under correct treatment.
      Immunodeficient women would benefit from closer care of their cervix. We think
      that combine therapy (e.g. laser and local interferon) would be more efficient in
      case of immunodeficiency.

PMID- 7827640
TI  - [Voluntary female sterilization in Europe and the world].
AB  - Voluntary sterilization is worldwide used about 138 millions women in
      reproductive ages, not only in the developing world. In the North American
      continent this method is very popular, and most European countries having
      legalized contraceptives and abortion consider sterilization as a necessary
      complementary measure for family planning purposes.

PMID- 7827641
TI  - [Words].
AB  - Society and our modern world are changing, and so does our language and its
      words, those carriers of our different trains of thought. Heavy or lightweight,
      last but not least, simple or pompous, easygoing or sophisticated, words can fail
      and cheat us, we can play with them or simply use them, they live their own life
      but we cannot live without them. They disappear or reappear, they sometimes don't
      have the same meaning for our patients as for us, and we have to strive and hear
      what they say and do not say... in so many words. Maybe the real change in our
      brave new world of high-tech communication would be to restore its true value to
      the patient-doctor relationship in a verbal and non-verbal exchange. Of course
      this goes without saying, but so much better when said!

PMID- 7827642
TI  - [Acceptability, tolerance and quality of life impact of cyproterone acetate
      treatment in female hirsutism. Comparison of 2 protocols in combination with oral
      or transdermal estradiol].
AB  - 67 women (aged 16-40) with hirsutism and/or other signs of hyperandrogenism
      (acne, androgenic alopecia, cycle disturbances) have been treated for one year
      with cyproterone acetate + estradiol. Patients have been randomly assigned to
      therapy with cyproterone acetate and estradiol valerate per or cyproterone
      acetate and transdermal estradiol. Acceptance, tolerance and effects on quality
      of life of this treatment have been assessed using a self questionnaire completed
      with questions for assessment for compliance. Among patients who have had a full
      course of treatment, 54 have fulfilled the end-of-study quality of life
      questionnaire. The queries allow calculation of a relational well-being score and
      of an emotional well-being score. The answers to the initial questionnaire show
      in a high percentage of patients emotional trouble (depressive state, anxiety,
      irritability) and disturbances in relational life. The hirsutism score has been
      found to be significantly correlated with anxious trouble but not with the global
      quality of life score. The treatment has resulted in a significant improvement in
      acceptance of being exposed to view (p < 0.01), self-assurance (p < 0.01) as well
      as emotional well-being score (p < 0.05), without any significant difference
      between the 2 therapeutics groups. Measurement of treatment acceptance with a
      visual analogic scale has been found globally very satisfactory by patients from
      the 2 groups. Compliance of treatment with transdermal estradiol turned out to be
      lesser in younger patients but is better in patients in whom emotional balance
      has been improved by therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7827643
TI  - Consensus statement on red cell transfusion. Royal College of Physicians of
      Edinburgh.

PMID- 7827644
TI  - Some moral problems in medicine.

PMID- 7827645
TI  - The German health care system at the crossroads.

PMID- 7827646
TI  - Economic evaluation and clinical uncertainty: response to Freemantle and Maynard.

PMID- 7827647
TI  - Costs, effects and C/E-ratios alongside a clinical trial.
AB  - A general approach is discussed to assess the uncertainty surrounding the cost
      effectiveness ratio (C/E-ratio) estimated on the basis of data from a randomised
      clinical trial. The approach includes the calculation of a 95% probability
      ellipse and introduces the concept of a so called C/E-acceptability curve. This
      last curve defines for each predefined C/E-ratio the probability that the C/E
      ratio found in the study is acceptable. The approach is illustrated by estimates
      of costs per life saved and costs per patient discharged alive on the basis of
      data from a phase II trial addressing the value of anakinra in treating sepsis
      syndrome.

PMID- 7827648
TI  - Peritoneal cytology for suspected acute appendicitis: an economic evaluation.
AB  - Suspected acute appendicitis is a common reason for surgery. Unfortunately,
      diagnosis is not always simple and, in recent years, considerable attention has
      been devoted to developing better diagnostic techniques. Peritoneal cytology is
      one such technique. It is simple, minimally invasive, and has been established as
      clinically effective. This paper reports on an economic evaluation of peritoneal
      cytology, carried out at Wellington Hospital, New Zealand. The analysis is based
      on two trials totalling 192 patients. The perspective taken initially is that of
      a hospital financial manager, seeking to minimise costs. In the first trial,
      there was a marginal increase in overall cost per person presenting with
      suspected acute appendicitis, from using the test. In the second, there was a
      reduction. In both trials there were significant health benefits--unnecessary
      operations were avoided, and necessary operations done more quickly. Also, the
      practice developed, in the second trial, of sending patients home immediately
      following a negative test result. This further increased savings. We then discuss
      the results from a broader perspective. We conclude that the additional personal
      benefits--less time convalescing, and lower mortality, on average--ensure that
      the benefits outweigh the costs of the test.

PMID- 7827649
TI  - Statistical analysis of cost outcomes in a randomized controlled clinical trial.
AB  - This paper suggests an approach to deal with an estimation problem which is often
      encountered in analyzing the longitudinal cost data gathered in a clinical trial.
      The source of that estimation problem is twofold: 1) a considerable number of
      missing data due to treatment-related withdrawal of severely affected patients
      with high health care costs in only one the treatment groups and 2) a heavily
      skewed cost distribution due to rare high-cost events. The approach is
      illustrated using data from a trial comparing 3 different drug regimes. In order
      to calculate costs per patient-year in case of selectively missing data we
      extrapolated the costs of patients with incomplete follow-up. Due to the skewness
      and the associated large variance in costs per patient-year, these costs cannot
      be analyzed using common parametric statistical methods relying on underlying
      normal distributions. A logarithmic transformation was performed to approximate a
      normal distribution, reduce the impact of extreme values and create similar size
      variances in the treatment groups. An ordinary least squares regression analysis
      of transformed data then standardized for differences in patient characteristics
      between the groups. For the retransformation, the so-called smearing estimate was
      used. This 'transformation-standardization-retransformation' approach enabled us
      to provide more consistent and efficient estimates of cost differences that were
      shown to be statistically significant and judged to be important.

PMID- 7827650
TI  - Experiences and reflections of former pediatric chief residents.

PMID- 7827651
TI  - Managed care coverage.

PMID- 7827652
TI  - I've always liked kids.

PMID- 7827653
TI  - Back pain in young athletes. Significant differences from adults in causes and
      patterns.
AB  - OBJECTIVES: To determine whether there are significant differences in the causes
      of back pain in young athletes compared with the general adult population and to
      review the diagnosis and assessment of young athletic adolescent patients who
      present with this complaint. DESIGN: Retrospective randomized case comparison
      study with two cohorts segregated by age and type of activity. SETTING: The
      adolescent sports medicine clinic of a children's hospital compared with the
      acute low back pain clinic of an orthopedic hospital. PATIENTS: One hundred
      adolescent athletes (aged 12 to 18 years; mean age, 15.8 years) with a chief
      complaint of low back pain were compared with 100 adults (aged 21 to 77 years;
      mean age, 31.9 years) with acute low back pain. INTERVENTIONS: None. MAIN OUTCOME
      MEASURES/RESULTS: Sixty-two percent of the adolescents had derangements of their
      posterior elements associated with the onset of back pain. Forty-seven percent of
      the 100 adolescents were ultimately shown to have a spondylolysis stress fracture
      of the pars interarticularis. By contrast, 5% of adult subjects were found to
      have spondylolysis associated with low back pain. Similarly, discogenic back pain
      was the final diagnosis in 48 of the 100 subjects in the adult group, while 11 of
      the 100 in the adolescent group had back pain attributable to disc abnormalities.
      Muscle-tendon strain accounted for back pain in 27% of the adults, while only 6%
      of the adolescents were diagnosed as having muscle-tendon strain. These
      differences were significant. Spinal stenosis and osteoarthritis as causes of
      back pain were encountered in 10% of the adults, while these conditions were not
      encountered in the children. CONCLUSIONS: There is a significant differences in
      the major causes of low back pain in young athletes compared with causes of low
      back pain in the general adult population. Physicians diagnosing back pain in
      young athletes must have a specific understanding of these differences to avoid
      incorrect diagnosis and harmful delays in proper treatment.

PMID- 7827654
TI  - Cardiopulmonary resuscitation in the delivery room. Associated clinical events.
AB  - OBJECTIVES: To determine (1) what percentage of infants require chest
      compressions and medications as part of resuscitation in the delivery room, (2)
      the associated clinical events contributing to neonatal depression, and (3) the
      neonatal outcome of such children. DESIGN: Observational study. SETTING: Urban
      county hospital. RESULTS: For 2 years, 39 (0.12%) of 30,839 infants were
      administered chest compressions and/or epinephrine as part of cardiopulmonary
      resuscitation in the delivery room. Fifteen were term infants and 24 were
      premature. Five term infants had evidence of severe fetal acidemia (FA)
      (umbilical cord arterial pH < 7.00 and/or base deficit > or = -14 mEq/L); two
      died secondary to severe brain injury, and the neurologic examinations showed
      abnormalities in the three survivors. The 10 infants without severe FA exhibited
      an uncomplicated neonatal course. Five infants had evidence of severe FA; the
      neurologic examination showed abnormalities in four. Of the remaining 19 infants
      without severe FA, four died and five additional infants have moderate to severe
      brain injury. Abnormal outcome was more likely to occur with severe FA (P <
      .002). The presumed clinical events contributing to the neonatal depression were
      severe FA (n = 10), malpositioning of the endotracheal tube (n = 5), and
      ineffective or improper initial ventilatory support (n = 24). CONCLUSIONS:
      Cardiopulmonary resuscitation in the delivery room, resulting in administration
      of chest compressions and medications, is a rare event. Approximately one third
      of the infants had evidence of severe FA; in the remaining two thirds,
      ineffective or improper initial ventilatory support was the presumed mechanism
      for the continued neonatal depression. The appropriate therapeutic response to
      continuing neonatal depression should be to optimize ventilatory support before
      administering chest compressions or medications.

PMID- 7827655
TI  - Signs and symptoms predicting acute otitis media.
AB  - OBJECTIVE: To determine whether acute otitis media can be distinguished from an
      uncomplicated upper respiratory tract infection by the symptoms of the children.
      DESIGN: Prospective cohort study. SETTING: Urban, pediatric primary care center
      in Turku, Finland. PATIENTS: Three hundred two children younger than 4 years
      (mean age, 2.1 years) attending day-care centers were followed up and examined
      during episodes of upper respiratory tract infection. The signs and symptoms of
      the children were recorded daily by the parents. MAIN RESULTS: The specificity
      and positive predictive value of earache for acute otitis media were 92% and 83%,
      respectively. However, 40% of the children with acute otitis media had no
      apparent earache. Restless sleeping had a specificity of 51% and a positive
      predictive value of 46% for acute otitis media. Thirty-one percent of the
      children with acute otitis media had no fever. Continuation of respiratory
      symptoms for several days after the first examination was significantly related
      with later development of acute otitis media. CONCLUSIONS: Earache in children
      with upper respiratory tract infection is indicative of acute otitis media, but
      the absence of earache does not preclude acute otitis media. Therefore, even in
      the absence of any signs and symptoms localized to the ear, all children at risk
      for acute otitis media should be examined during upper respiratory tract
      infection, and if respiratory symptoms persist for several days after the initial
      visit, a reexamination should be performed. Restless sleeping and fever are of no
      value in distinguishing acute otitis media from an uncomplicated upper
      respiratory tract infection.

PMID- 7827656
TI  - Penicillin-resistant pneumococci from pediatric patients in the Washington, DC,
      area.
AB  - OBJECTIVE: To assess the prevalence and antimicrobial susceptibility of
      penicillin-resistant pneumococci (PRP) isolated from patients in a pediatric
      hospital. METHODS: All (108) isolates of Streptococcus pneumoniae recovered from
      usually sterile body sites between June 1, 1992, and May 31, 1993, were screened
      for susceptibility to penicillin by the E-test method. Minimum inhibitory
      concentrations of penicillin and other antibiotics were also determined by an
      agar dilution method for 10 PRP and 22 penicillin-susceptible strains. RESULTS:
      Fourteen isolates (12.9%) were PRP by the E-test; nine of these (8.3%) were
      intermediately resistant and five (4.6%) were highly resistant. All strains were
      sensitive to rifampin and vancomycin. Increased frequency of resistance to oral
      and parenteral cephalosporins and carbapenems was found among PRP; for most of
      these antibiotics, resistance exceeded 40% of the PRP. In addition, 20% of the
      PRP were resistant to macrolides and all penicillin-susceptible and PRP were
      resistant to a combination of trimethoprim and sulfamethoxazole. CONCLUSIONS: The
      decreased susceptibility to oral and parenteral cephalosporins, macrolides, a
      combination of trimethoprim and sulfamethoxazole, and carbapenems creates a
      significant problem in the treatment of pneumococcal infections in both
      ambulatory and hospitalized patients.

PMID- 7827657
TI  - Symptoms and spontaneous passage of esophageal coins.
AB  - OBJECTIVES: To determine whether coins located in different portions of the
      esophagus differ in their likelihood of spontaneous clearance, and to determine
      the frequency of asymptomaticity among children with esophageal coins. DESIGN:
      Retrospective case review. SETTING: Pediatric academic tertiary care center.
      PATIENTS: All 73 children presenting in an 18-month period to a pediatric
      emergency department for coin ingestion whose roentgenographic evaluation
      revealed an esophageal coin. INTERVENTIONS: None. OUTCOME MEASURES: Hospital
      records of all children were reviewed for demographic information, coin
      denominations, esophageal locations of ingested coins based on roentgenographic
      reports, performance of invasive removal procedures, and the presence or absence
      of signs and/or symptoms. RESULTS: All of the 58 children with proximal or middle
      esophageal coins underwent invasive removal procedures, while nine (60%) of 15
      distal esophageal coins passed into the stomach spontaneously (P < .001). Five
      children (7%) were asymptomatic. CONCLUSIONS: Proximal and middle esophageal
      coins should be promptly removed, as per present practice. Children with distal
      esophageal coins should be observed up to 24 hours before an invasive removal
      procedure, since many will spontaneously clear their coins. Since esophageal
      coins may be asymptomatic, all children who have swallowed coins should undergo
      roentgenographic evaluation.

PMID- 7827658
TI  - Developmental and nutritional status of internationally adopted children.
AB  - OBJECTIVES: To assess the relationship between developmental status of
      international adoptees at the time of entry into the United States and their
      nutritional status and concurrent medical problems. DESIGN: Prospective study.
      SETTING/PATIENTS: One hundred twenty-nine internationally adopted children
      attending the International Adoption Clinic at the Floating Hospital for
      Children, Boston, Mass, underwent detailed developmental assessments,
      anthropometric measurements, and medical examinations. RESULTS: The
      anthropometric measurements of the international adoptees were below the means
      for weight, height, and head circumference based on standards of the World Health
      Organization. Only 65 children (50%) were developmentally normal. Gross motor
      delays were identified in 43 children (33%), fine motor delays in 52 (40%),
      language delays in 23 (18%), cognitive delays in 21 (16%), and global delays in
      18 (14%). The severity of delays were related to z scores for weight, height, and
      head circumference. The 36 children with medical problems had lower z scores
      compared with healthy children and were more likely to have delayed development.
      CONCLUSIONS: Careful developmental and growth screening of internationally
      adopted children at entry into the United States identifies adopted children at
      entry interventions and close follow-up. Longitudinal studies of internationally
      adopted children may provide evidence about the reversibility of growth and
      developmental delays, findings applicable to any environmentally deprived child.

PMID- 7827659
TI  - Fetal alcohol syndrome at the turn of the 20th century. An unexpected explanation
      of the Kallikak family.
AB  - At the turn of the 20th century, studies of a family known in the literature as
      the Kallikaks were used to document the hereditary nature of mental retardation,
      poverty, and antisocial behavior. This family was said to authenticate eugenic
      theory, which states that heritable characteristics carried by individuals on
      "independent unit characters are unalterable determinants of behavior and
      performance. A review of the original Kallikak data, however, suggests that in
      utero exposure to alcohol rather than heredity contributed significantly to the
      transgenerational learning failure seen throughout the Kallikak pedigree.
      However, eugenic theory was so thoroughly accepted that the promotion and
      acceptance of "hereditary feeblemindedness" as the principal cause of the
      developmental problems in the affected offspring smothered the research efforts
      on in utero effects of alcohol until long after the eugenic concepts were
      abandoned later in the century.

PMID- 7827660
TI  - Teaching newborn medicine to third-year medical students. Use of a checklist.
AB  - OBJECTIVE: To determine if use of a checklist during the third-year medical
      student's newborn medicine rotation within the pediatric clerkship affected
      grades, end-of-course examination scores, or perceptions of the new-born clinical
      experience before and after use of this teaching aid. METHODS: The checklist
      contained 46 newborn medicine-related skills and concepts and required staff
      review. A postclerkship questionnaire was used to assess the student's perception
      of all components of the clinical clerkship. A standardized test was used to
      assess clinical knowledge. The clerkship grade was based on test scores (30%) and
      clinical performance (70%). RESULTS: All students (N = 321) returned the
      postclerkship questionnaire from July 1, 1988, to June 30, 1990, and the
      checklist plus questionnaire (N = 294) from July 1, 1990, to June 30, 1992.
      During both periods, the curriculum and clinical experience remained unchanged.
      Although there was no change in grade distribution, mean final examination score
      (P < .011) and student perception of the nursery portion of the clerkship (P <
      .01) improved significantly after we began using the checklist. "Poor" ratings of
      the nursey experience decreased from 12% (1988 to 1989) to 3% (1991 to 1992), and
      "excellent" ratings increased from 13% to 24%. In addition, examination
      performance on specific examination questions appeared related to completion of
      checklist items (r = .68, P < .016). CONCLUSIONS: Use of a readily available
      checklist, to remind students and faculty of the skills and concepts to be
      mastered during the nursey portion of the clerkship, did not impact final grades,
      although information transfer and student perception of the clinical experience
      improved. We speculate that clear delineation of readily available objectives
      focuses students and staff, decreases anxiety, and provides a sense of
      accomplishment.

PMID- 7827661
TI  - Radiological case of the month. Myositis ossificans circumscripta.

PMID- 7827662
TI  - Picture of the month. Erysipelas.

PMID- 7827663
TI  - Pathological case of the month. Sinus histiocytosis with massive lymphadenopathy
      (Rosai-Dorfman disease).

PMID- 7827664
TI  - Kawasaki syndrome in Washington State. Race-specific incidence rates and
      residential proximity to water.
AB  - OBJECTIVES: To calculate race-specific incidence rates of Kawasaki syndrome (KS)
      and to assess the association of KS with residential proximity to water in
      Washington State. DESIGN: Incidence study over 4 1/2 years, using cases
      identified with a new statewide hospital data set and a case-control study.
      SETTING: King, Pierce, and Snohomish counties in Washington State. PATIENTS: One
      hundred twelve population-based incident cases meeting Centers for Disease
      Control and Prevention criteria for KS. MAIN OUTCOME MEASURES: Race-specific KS
      incidence rates and distance to permanent bodies of water among KS cases and
      matched controls. RESULTS: For the years 1985 through 1986 and 1987 through 1989,
      the annual KS incidence rates were 6.5 and 15.2 per 100,000 children younger than
      5 years, respectively. Rates were highest among Asian Americans (33.3 per 100,000
      children younger than 5 years in the 1987-1989 period), followed by blacks and
      whites (23.4 and 12.7 per 100,000 children younger than 5 years, respectively).
      The median distance to water did not differ between cases and controls and the
      proportion of cases living within 150 yd (135 m) of water was no greater than
      that of controls (odds ratio, 1.0; 95% confidence interval, 0.1 to 20.9).
      CONCLUSIONS: With complete ascertainment of incident-hospitalized cases of KS,
      the race-specific rates are among the highest documented in the United States.
      The rate among Asian Americans was less than that found in Japan, perhaps due to
      differences in environmental exposures or variations in susceptibility among
      different Asian ethnic groups. Although we found no association with permanent
      bodies of water, future studies of KS should include home inspection to assess
      exposure to temporary collections of standing water.

PMID- 7827665
TI  - A descriptive study of prune belly in New York State, 1983 to 1989.
AB  - OBJECTIVE: To determine the prevalence and spectrum of prune belly in a defined
      population. DESIGN: Population-based descriptive study using New York State's
      Congenital Malformations Registry. SETTING: The Congenital Malformations Registry
      is a statewide registry of children diagnosed as having congenital anomalies
      before the age of 2 years. PATIENTS: Infants with the diagnosis of prune-belly
      syndrome born during the years 1983 to 1989 to women who were New York State
      residents and verified by medical record review. MAIN OUTCOME MEASURES: The live
      birth prevalence of prune belly for the total population and for population
      subgroups, such as race, sex, plurality, and maternal age. The occurrence of
      other malformations with prune belly. RESULTS: Sixty cases of prune belly were
      ascertained (50 male and 10 female). The live birth prevalence was 3.2 per
      100,000 and declined over the time period. The prevalence was higher in males,
      5.1 per 100,000, than females, 1.1; and higher in blacks, 5.8, than whites, 2.6.
      The live birth prevalence of prune belly in twins, 12.2 per 100,000, was four
      times higher than that found in singletons, 3.0. More than 36 (60%) of patients
      died, most in the first week. Forty-two (70%) of patients had one of the commonly
      described associated defects; pulmonary hypoplasia was the most common. Almost
      one third of patients had defects other than those typically associated with
      prune belly. CONCLUSIONS: Twins, blacks, and children born to younger mothers
      appear to be at higher risk. Mortality remains high, especially early with many
      deaths due to pulmonary hypoplasia. Further studies should include stillborns and
      terminated pregnancies.

PMID- 7827666
TI  - Echocardiographic-guided internal jugular venous cannulation in children with
      heart disease.
AB  - OBJECTIVE: To determine if cannulation of the internal jugular vein (IJV) with
      echocardiographic guidance increases the success and decreases the complications
      of the procedure when performed in children with heart disease. DESIGN: Twenty
      five consecutive pediatric patients with heart disease who underwent IJV
      cannulation with echocardiographic guidance between September 1986 and March
      1992. SETTING: University hospital referral center serving a four-state area.
      PATIENTS AND OTHER PARTICIPANTS: Ambulatory patients were admitted for this
      procedure and then discharged at its completion; others included hospitalized
      patients. All patients were between the ages of 6 weeks and 21.8 years. All
      patients underwent IJV cannulation performed by a member of the Pediatric
      Cardiology Division at the University of Minnesota, Minneapolis. All patients
      either underwent heart transplant, and IJV access was obtained to perform an
      endomyocardial biopsy or had congenital heart disease, and the IJV was cannulated
      to perform a heart catheterization. Written consent was obtained either from the
      patient, if 18 years of age or older, or a parent or legal guardian.
      INTERVENTION: Cannulation of the IJV using echocardiographic guidance. MAIN
      OUTCOME MEASURES: Would IJV cannulation with echocardiographic guidance improve
      safety and diminish complications of the procedure when performed in pediatric
      patients with heart disease? We compared the results of our evaluation with
      published results in which echocardiographic guidance was not used. RESULTS:
      Cannulation of the IJV with echocardiographic guidance was performed successfully
      on 138 occasions in 25 pediatric patients. There were no lasting complications
      and no deaths using this method of venous access. CONCLUSIONS: As in the adult
      population, IJV cannulation with the assistance of echocardiography increases the
      success of the procedure and decreases the number of complications. Furthermore,
      echocardiographic guidance allows for repeated IJV cannulation in pediatric
      patients, regardless of age.

PMID- 7827667
TI  - Seasonal respiratory viral infections. Impact on infants with chronic lung
      disease following discharge from the neonatal intensive care unit.
AB  - OBJECTIVE: To determine the frequency and severity of acute respiratory
      infections in infants with bronchopulmonary dysplasia following discharge from
      the neonatal intensive care unit. DESIGN: A prospective cohort study of 30 oxygen
      dependent children who were younger than 2 years (mean age, 9.8 months; range, 3
      to 24 months) were studied from September 1990 through April 1991.
      MEASUREMENTS/RESULTS: During the study, 101 (90.2%) of 112 visits for illness
      were prompted by new or worsening respiratory symptoms. Diagnoses included upper
      respiratory tract infection (30.4%), otitis media (26.0%), pneumonia (11.1%),
      acute exacerbation of bronchopulmonary dysplasia (10.4%), reactive airway disease
      (9.6%), and bronchiolitis (5.9%). Among these children, an increase in the
      fraction of inspired oxygen was necessary during 43% of visits. Ten children were
      hospitalized on 25 occasions for a mean of 37.6 hospital days per child (range, 1
      to 107 days), and mean length of stay for each hospitalization was 15 days
      (median, 6 days). Five children were admitted to the pediatric intensive care
      unit. Respiratory viruses isolated included respiratory syncytial virus (n = 7),
      parainfluenza 3 virus (n = 3), and adenovirus (n = 2). No isolates of influenza A
      or B were detected. Anthropometrics at study entry and study end were converted
      to z scores as descriptors of weight for age, height for age, and weight for
      height. Growth improved during the 8 months of the study; however, overall, the
      children were leaner at study end than at study entry. CONCLUSIONS: In children
      with bronchopulmonary dysplasia, respiratory viral infections led to significant
      morbidity, which included long and frequent hospitalizations during the peak of
      the respiratory viral season. Although weight and linear growth increased
      throughout the study, patients were leaner at study conclusion than at study
      entry.

PMID- 7827668
TI  - Indications for Neisseria gonorrhoeae cultures in children with suspected sexual
      abuse.
AB  - OBJECTIVE: To determine the clinical predictors of Neisseria gonorrhoeae
      infection in children examined for sexual abuse. DESIGN: Retrospective review of
      a prospective management plan. SETTING: A 240-bed children's hospital with 36,000
      emergency department visits per year. INTERVENTION: In 1988, a Pediatric
      Emergency Medicine Department protocol was introduced for the examination of
      children who present with complaints suggestive of sexual abuse. RESULTS: From
      January 1990 through December 1991, the records of all children less than 12
      years of age examined for suspected sexual abuse were reviewed. Vaginal/urethral,
      oral, and rectal cultures for N gonorrhoeae were performed in 316 children. Seven
      children (2.2%) had a total of 12 positive cultures: seven vaginal/urethral, four
      rectal, and one oral. Evidence of vaginal/urethral discharge on physical
      examination was the best predictor of N gonorrhoeae infection (sensitivity, 100%;
      specificity, 88%; positive predictive value, 16%; and negative predictive value,
      100%). Historical and physical evidence of discharge was significantly associated
      with N gonorrhoeae infection (P < .0006 and P < .000001, respectively).
      CONCLUSIONS: Children less than 12 years of age examined for sexual abuse who did
      not have evidence on physical examination of vaginal or urethral discharge were
      found to have a 100% probability of having negative vaginal/urethral, oral, and
      rectal N gonorrhoeae cultures. These findings do not support the practice of
      obtaining cultures for N gonorrhoeae routinely in all children who present for
      evaluation of possible sexual abuse.

PMID- 7827669
TI  - Theophylline effects on cognition, behavior, and learning.
AB  - OBJECTIVE: To compare a group of hospitalized asthmatic children taking
      theophylline with a similar group of hospitalized nonasthmatic children on
      standardized measures of distractibility, attention, hyperactivity, and academic
      achievement. DESIGN: Standardized psychological tests were used to measure
      cognition, attention, and learning, and results for the two groups were compared.
      SETTING: All subjects were hospitalized in an intermediate care facility.
      PATIENTS: Up to 63 asthmatic children taking theophylline were compared with a
      group of 46 nonasthmatic children matched for age, sex, socioeconomic status, and
      full-scale IQ. Children with head injuries, mental retardation, or known learning
      disabilities were not included. INTERVENTIONS: All asthmatic children and none of
      the nonasthmatic children maintained therapeutic levels of theophylline during
      the evaluation period. MAIN OUTCOME MEASURES: Independent t tests were used to
      examine differences between groups on psychological tests of cognition,
      attention, and learning. RESULTS: No significant differences were found between
      groups on any variables at the 95% level of confidence. CONCLUSIONS: While
      idiosyncratic side effects of theophylline are possible, most children are not
      more hyperactive, distractible, short of memory, different in academic
      achievement, or more impulsive than other children with chronic illness.

PMID- 7827670
TI  - Hospitalization vs outpatient treatment of young febrile infants: 10-year
      comparison.

PMID- 7827671
TI  - Improper mixing of formula due to reuse of hospital bottles.

PMID- 7827672
TI  - Erythromycin-induced carbamazepine toxicity: a continuing problem.

PMID- 7827673
TI  - [The modelling of the initiation of genetic damages from low doses of ionizing
      radiation in eukaryotic cells based on the concept of the existence of
      evolutionary reserve cells].
AB  - The model predicting quantitatively a dose response for genetic lesions in low
      dose range is presented. The model is based on the concept of programmed
      initiation of the genetic damage in the subpopulation of specific cells of
      "evolutionary reserve" (CER). It is demonstrated that complex shape of dose
      response curve results from superposition of processes in different
      subpopulations within exposed cell population, mainly in CER. The model allows us
      to explain the minimum observed in the dose-response curve at doses corresponding
      to one (on the average) event of energy deposition per CER with spontaneous
      aberrations. The equation for dose-response function for dicentrics describes
      satisfactory experimental observations. Advantage of proposed equation is that it
      does not deal with free parameters to fit the data. They are determined
      independently by using known physical and biological characteristics. The data
      described allow us to suggest that sensitive body for CER is a cell as a whole.
      Probably, programmed initiation of genetic lesions in CER requires both two hits
      at cell membrane and radiation effect on cell nucleus.

PMID- 7827674
TI  - [The mechanism of the initiation of low-dose effects].
AB  - A mechanism for initiation effects is proposed. This is based on the theory of
      non-specific response of cells to damaging influences, which has been developed
      by the author previously. The effects (adaptive response, stimulation of
      proliferation, etc.) are believed to be initiated by disturbance of the functions
      of plasmatic and intracellular membranes which decreases the concentration of low
      molecular cellular metabolites and affects their compartmentation. The presence
      of a lower threshold of the effects, the maximum in the dose dependence as well
      as dose rate and dose value effects in the range of low doses are explained.

PMID- 7827675
TI  - [The effect of low doses of ionizing radiation on the DNA in the spleen in the
      irradiation of mice].
AB  - The research of low dose gamma-irradiation 137Cs effect on mice line F1 has been
      carried out under two different intensities: 0.6 cGy per day (dose range 0.6-9.6
      cGy) and 6.0 cGy per day (dose range 6.0-60 cGy). High molecular DNA was isolated
      from spleen of irradiated and intact mice and analyzed by DNA retention method to
      nitrocellulose filters under physiological ionic strength. Increase in percentage
      of DNA retention after mice irradiation by doses of 0.6-5.4 cGy with maximum of
      1.2 has been found. In dose range 6.0-24 cGy maximum of DNA retention has been
      observed at dose of 6.0 cGy. DNA preparation did not contain single-strand
      breaks. It is supposed that the phenomena of increase in percentage of DNA
      retention is the result of its compactization during the process of adaptive cell
      response to low dose ionizing radiation exposure.

PMID- 7827676
TI  - [Postradiation structural changes in the thymocyte and lymphocyte plasma
      membranes in the fractional irradiation of rats].
AB  - On days 1 and 4 after fractionated irradiation of rats with dose of 0.75 Gy
      changes in thymocyte and lymphocyte plasma membrane structures were studied.
      Structural parameters of fluorescence probe auramin binding, viscosity of free
      lipids and lipids bound with integral proteins as well as structural changes of
      membrane protein structure were determined. It was shown that after exposure to
      low doses the changes in membrane protein structures occurred both in thymocytes
      and lymphocytes. The changes in viscosity of membrane lipids and patterns of
      auramin binding were more pronounced in lymphocytes than in thymocytes. It is
      suggested that radiosensitivity of lymphocytes is higher than that of thymocytes.

PMID- 7827677
TI  - [The glutathione content and glutathione-S-transferase activity in the organs and
      blood of rats following chronic irradiation at low doses].
AB  - The effect of chronic low dose-rate irradiation with X-rays up to total doses of
      2.58, 5.16, 6.46, 7.75, 10.32, 12.92 mC/kg on glutathione content and glutathione
      S-transferase activity in Wistar rats organs, different by radiosensitivity, was
      studied 1 h after exposure. It has been shown that level of oxidized and reduced
      glutathione forms was not changed after exposure to 2.58 mC/kg, was enhanced in
      kidney and brain tissues after exposure to 5.16 and 6.46 mC/kg and was decreased
      in brain, lungs, small intestines and blood serum after ray exposures to higher
      doses. Inhibition of glutathione-S-transferase activity was found in liver,
      kidneys and spleen.

PMID- 7827678
TI  - [The role of the sex hormones in regulating the spermatogenesis process in
      different strains of mice irradiated at low doses of gamma quanta].
AB  - Intact BALB/c and CBA mice distinct in the total number of germ cells and
      testosterone level in blood plasma were exposed to doses of 0.1 and 0.25 Gy.
      Being tested 4-8 days after irradiation the BALB/c mice display compensatory
      protective reaction which promote the maintenance of the germ cell number by
      active division of all spermatogonia types including the reserve ones. The CBA
      mice use the reserve later and only when the cells have reduced their
      proliferation activity or died. Testosterone plays a significant role in the
      process as the increase in its concentration stimulates proliferation activity
      and promotes mitosis block.

PMID- 7827679
TI  - [The possibilities of using biological dosimetry methods for the retrospective
      assessment of dosages in relation to the sequelae of the accident at the
      Chernobyl Atomic Electric Power Station. An assessment of the dosages based on an
      analysis of unstable chromosome aberrations].
AB  - The problem of retrospective dose assessment in connection with the Chernobyl
      accident is discussed. Existing methods of dose quantification based on the
      analysis of unstable aberrations in blood lymphocytes are discussed in details.
      Starting from the own data it is concluded that unstable aberration technique
      could not be applied to verify individual doses for ameliorators as well as for
      inhabitants of contaminated areas.

PMID- 7827680
TI  - [The possibilities of using biological dosimetry methods for the retrospective
      assessment of dosages in relation to the sequelae of the accident at the
      Chernobyl Atomic Electric Power Station. An assessment of the dosages based on an
      analysis of stable chromosome aberrations].
AB  - The problem of retrospective dose assessment in connection with the Chernobyl
      accident is discussed. Reasons justifying the applicability and advantages of
      technique based on the analysis of stable aberrations in blood lymphocytes are
      given. Two modern methods for registration aberrations of these registration,
      namely fluorescence in situ hybridization and full karyotyping of G-banded
      chromosomes are considered in details.

PMID- 7827681
TI  - [The results of a cytogenetic examination performed in different years on those
      who worked in the cleanup of the aftermath of the accident at the Chernobyl
      Atomic Electric Power Station].
AB  - Persons participated in the Chernobyl accident amelioration in the years of 1986
      1987 were examined cytogenetically either in 1987 (group 1) or in 1990-1992
      (group 2). The frequency of chromosome aberrations in cultured peripheral
      lymphocytes is found to be significantly lower in group 2 in comparison with
      group 1, being increased in both exposed groups as compared to the control one.
      The data are obtained in favour of hypothesis on chromosome instability of
      exposed individuals. On the base of cytogenetic data the collective dose received
      by amelioraters was calculated.

PMID- 7827682
TI  - [The adaptive reaction of the blood lymphocytes in persons subjected to chronic
      radiation exposure at low doses].
AB  - The changes in the PHA-stimulated human blood lymphocytes of the peoples from
      Moscow and from polluted after Chernobyl disaster Bryansk region were studied.
      The decrease in lymphocyte mitotic index in residents from polluted regions was
      revealed. Moscow population was not distinguished from Bryansk region population
      by the frequency of cells with micronuclei. There was also no difference in
      frequency of micronuclei after 1 Gy irradiation of the these populations. The
      adaptive response (irradiation with a dose of 0.05 Gy followed by 1.0 Gy
      irradiation 5 hours later) was studied. The decrease in the number of individuals
      with adaptive response and appearance of the individuals with increased
      radiosensitivity in the population of polluted regions were observed. There was
      no such subpopulation among the Moscow residents. So, firstly, low dose chronic
      irradiation is not an adaptive factor; secondly, the determination of adaptive
      response can be methodological procedure for the revealing the changes which were
      induced by low dose chronic irradiation (accompanied by other environment
      agents).

PMID- 7827683
TI  - [The formation of an adaptive response in children exposed to the effect of low
      doses of radiation as a result of the accident at the Chernobyl Atomic Electric
      Power Station].
AB  - The ability of lymphocytes to form an adaptive response in cells of the children
      which were exposed to small radiation doses during the Chernobyl accident was
      studied by hydroxyapatite chromatography of cell lysates. Ten children living in
      the area with high radiation level (Bryansk region) and seventeen children living
      in the area with natural radiation level (Bryansk region too) were examined. No
      difference in cell ability to form adaptive response was found in both children
      group.

PMID- 7827684
TI  - [The genetic monitoring of populations of brown frogs inhabiting radionuclide
      contaminated regions of the Republic of Byelarus].
AB  - Genetic monitoring of brown frog populations inhabiting radiocontaminated areas
      of Belarus (contamination range: 177-2331 kBq/m2 for 137Cs; 3.7-284 kBq/m2 for
      90Sr) has shown that the frequency of aberrant metaphases in bone marrow cells of
      animals from the contaminated areas is 3 to 10 times as much as that of the
      control, aberration load of cells being also higher. The aberration spectrum
      differs from a spontaneous one. There is no strict dependence of the yield of
      cytogenetic damages on the contamination.

PMID- 7827685
TI  - [The cytogenetic effect in the cells of the needles of the common pine from
      irradiation resulting from the accident at the Chernobyl Atomic Power Station].
AB  - The consequences of Pinus sylvestris irradiation were studied since 1987-1990.
      The chromosome aberrations in needle cells and morphological changes are annually
      observed at the same level, that confirms the continuous character of mutagenesis
      and morphogenesis. It is concluded that the big pool of damages is caused by
      radiation, one part of them is realized in chromosome aberration during the first
      vegetation after irradiation. The other part of them is transferred by division
      during the initial cell bud differentiation to the specialized cells and is
      realized to aberrations during the following vegetative periods.

PMID- 7827686
TI  - [The dynamics of the frequency of cytogenetic disorders in micropopulations of
      murine rodents inhabiting the region of the accident at the Chernobyl Atomic
      Electric Power Station].
AB  - Cytogenetic examination of some species of Muridae from Chernobyl region was
      carried out in 1986-1993. It was revealed that the dynamic of cytogenetic
      aberrations in cells of animals from territories with distinct level of
      radioactive contamination differed.

PMID- 7827687
TI  - [The micronucleus frequency in the somatic cells of murine rodents residing in a
      30-kilometer area of the Chernobyl Atomic Electric Power Station].
AB  - The chromosome aberration frequency in murine somatic cells was studied. Animals
      from natural populations as well as laboratory mice exposed within the ten
      kilometers zone of the Chernobyl accident were examined. Increase in micronuclei
      rate in bone marrow cells, erythrocytes of peripheral blood and hepatocytes was
      found in animals exposed to more high background radiation. Under chronic
      exposure the pattern of effect dependence on dose rate was similar both in
      somatic and sex cells.

PMID- 7827688
TI  - [The dose dependence of the induction of chromosome aberrations in those who
      worked in the cleanup of the Chernobyl accident].
AB  - The method of biological dosimetry based on registration of frequency of
      chromosome aberrations in peripheral lymphocytes was proven to be a valuable
      technique for estimation of large absorbed doses. In the case of low absorbed
      doses or low dose rate the suitability of this method is restricted because of
      deficiency of suitable dose-response curve for yield of chromosome aberrations.
      In this work chromosome aberration rate was estimated in 31 ameliorators of the
      Chernobyl accident with the known data of physical dosimetry in the range of 12
      30 cGy. Linear dependence of induction of chromosome aberrations was found in
      this dose range. The coefficients for induction of dicentrics and all unstable
      aberrations of chromosome type was found to be 1.4 +/- 0.4 and 7.2 +/- 1.2 per
      100 cells per 1 Gy, respectively.

PMID- 7827689
TI  - [An ecological and geographical test of the seed offspring of Viola matutina
      Klok. from a 30-kilometer area of the accident at the Chernobyl Atomic Electric
      Power Station].
AB  - The generation of seeds of two populations of Viola matutina Klok. sampled from
      plants growing within the thirty-kilometers zone of the Chernobyl accident (the
      reproduction of seeds in 1988) was investigated in the north nursery in
      Syktyvkar. The decrease of sterile pollen and embryonic lethality among the
      plants from the strongly contaminated site (exposure rate (1075-1434) pC/(kg.s)
      May 1987) was registered. It is suggested that this phenomenon is the result of
      the elimination of genetic damages in the course of seed forming in this
      population under radiation stress.

PMID- 7827690
TI  - [Statistical approaches to the analysis of multivariate heterogeneous biological
      systems].
AB  - To describe multivariate heterogeneous biosystems and their reactions to various
      impacts and to compare the objects with different complexity the integral
      characteristics are proposed. The characteristics can be obtained by means of non
      standard statistical approaches: variants of correlation analysis with the use of
      Fisher's Z-transformations followed by convolution and Mahalanobis
      multidimensional intervals. Applicability of these approaches to medical and
      biological problems is shown.

PMID- 7827691
TI  - Electron spin resonance studies of nitrosyl haemoglobin in human liver, colon and
      stomach tumour tissues.
AB  - Iron nitrosyl haemoglobin (HbFeNO) gives well defined ESR spectra, and can be
      detected at room temperature, in contrast with most transition metal complexes of
      biological importance. This is because the unpaired electron remains strongly
      localised on the NO ligand. It is of importance because it proves the formation
      of nitric oxide, which unfortunately cannot be detected directly by ESR
      spectroscopy. We have studied a range of tissues taken from human liver, colon
      and stomach tumours which have been directly frozen to 77K and studied at 77K.
      The results show that formation of HbFeNO is rare in tissue adjacent to tumour
      tissue ("peripheral tissue"), but is always found in necrotic central regions, if
      present. However, in several cases, HbFeNO was also detected in tumour tissue
      which was not necrotic. Two factors contribute to the formation of this complex.
      One is the presence of "free" NO molecules in the cellular regions, and the other
      is the presence of deoxyferrohaemoglobin, since neither ferrihaemoglobin nor
      oxyhaemoglobin react to give this complex. [For systems containing myoglobin
      these comments include the possibility of the formation of nitrosylmyoglobin,
      which gives very similar ESR spectra.

PMID- 7827692
TI  - Nitric oxide reversibly suppresses xanthine oxidase activity.
AB  - The effects of nitric oxide (NO) on xanthine oxidase (XOD) activity and the
      site(s) of the redox center(s) affected were investigated. XOD activity was
      determined by superoxide (O2-) generation and uric acid formation. NO reversibly
      and dose-dependently suppressed XOD activity in both determination methods. The
      suppression interval also disclosed a dose-dependent prolongation. The
      suppression occurred irrespective of the presence or absence of xanthine;
      indicating that the reaction product of NO and O2-, peroxynitrite, is not
      responsible for the suppression. Application of synthesized peroxynitrite did not
      affect XOD activity up to 2 microM. Methylene blue, which is an electron acceptor
      from Fe/S center, prevented the NO-induced inactivation. The results indicate
      that NO suppresses XOD activity through reversible alteration of the flavin
      prosthetic site.

PMID- 7827693
TI  - Metabolism of ethanol to 1-hydroxyethyl radicals in rat liver microsomes:
      comparative studies with three spin trapping agents.
AB  - Metabolism of ethanol to 1-hydroxyethyl radicals by rat liver microsomes was
      studied with three nitrone spin trapping agents (POBN, PBN, and DMPO) under
      essentially comparable conditions. The data indicate that POBN was the superior
      spin trapping agent for 1-hydroxyethyl radicals, and that DMPO was least
      efficient. Addition of deferoxamine completely prevented detection of 1
      hydroxyethyl radicals with PBN or DMPO, but caused only 50% decrease in EPR
      signals when POBN was the spin trap. However, superoxide dismutase only decreased
      1-hydroxyethyl radical formation when POBN was the spin trap. Other experiments
      demonstrated that POBN was the most effective of these nitrones for reduction of
      Fe(III) in aqueous solutions. Furthermore, 1-hydroxyethyl radical adducts were
      formed when POBN was added to mixtures of ethanol, phosphate buffer, POBN and
      FeCl3, but this effect did not occur with either PBN or DMPO. Thus, these data
      indicate that undesirable effects of POBN on iron chemistry may influence results
      of spin trapping experiments, and complicate interpretation of the resulting
      data.

PMID- 7827694
TI  - Dysfunction of mouse liver mitochondria induced by 2,2'-azobis-(2-amidinopropane)
      dihydrochloride, a radical initiator, in vitro and in vivo.
AB  - Mouse liver mitochondria were uncoupled in a time dependent by intraperitoneal
      injection of a radical initiator, 2,2'-azobis-(2-amidinopropane) dihydrochloride
      (AAPH) (100 mg/kg). State 3 respiration, ADP/O ratio and respiratory control
      ratio (RCR) were decreased 30 min after injection but there was no effect on
      state 4 respiration. Lipid peroxidation was increased and oxidative
      phosphorylation was uncoupled at one hr after drug injection but gradually
      recovered to normal levels after 14 hr in vivo. State 3 respiration, RCR and
      ADP/O ratio but not state 4 respiration of isolated mouse mitochondria were
      inhibited by short term incubation with AAPH in vitro. This inhibitory action was
      concentration dependent (ID50 = 5 mM) but was not prevented by alpha-tocopherol.
      AAPH had no effect on electron transport or the membrane potential of these
      isolated mitochondria. However, mitochondria were uncoupled via lipid
      peroxidation and swelling by long term incubation with AAPH. These inhibitory
      effects of AAPH were reduced by its spontaneous degradation not only in vitro but
      also in vivo. Thus AAPH induces mitochondrial dysfunction by direct action in the
      early period of treatment and free radicals produced from AAPH mediate
      mitochondrial swelling via lipid peroxidation in the late period. From these
      findings, it is concluded that mitochondrial phosphorylation plays an important
      role in the pathogenesis of liver injury induced by AAPH and that radicals
      generated by AAPH might be a source of liver injury and mitochondrial dysfunction
      in vivo.

PMID- 7827695
TI  - Biological reduction of aromatic nitroso compounds: evidence for the involvement
      of superoxide anions.
AB  - The in vitro formation of phenylhydronitroxide and 2-methylphenylhydronitroxide
      free radicals from nitrosobenzene (NB) and 2-nitrosotoluene (NT), respectively,
      in either red blood cells (RBC) or RBC hemolysates, was confirmed by electron
      spin resonance spectroscopy (ESR). Free radicals were generated nonenzymatically
      from reaction of the respective nitroso compounds with a number of biological
      reducing agents as corroborated by model studies of NB or NT with NAD(P)H. Under
      aerobic conditions, phenylhydronitroxide and 2-methylphenylhydronitroxide
      underwent a subsequent one-electron transfer to oxygen, which then resulted in
      the formation of superoxide anion (O2-). The latter product was confirmed by the
      superoxide dismutase (SOD)-inhibitable reduction of cytochrome c (cyt c).
      Apparently, oxygen is needed for continuous formation of the hydronitroxide
      radical derivatives. On the other hand, under anaerobic conditions, no
      phenylhydronitroxide radical was generated from NB in the presence of NADH, but
      the formation of phenylhydroxylamine from NB was detected by the absorption
      spectrometry. These results suggest that oxygen is a preferential electron
      acceptor for hydronitroxide radical derivatives.

PMID- 7827696
TI  - Radical intermediates and antioxidants: an ESR study of radicals formed on
      carnosic acid in the presence of oxidized lipids.
AB  - Carnosic acid, an antioxidant extracted from rosemary, is shown to produce
      radicals when in contact with oxidized methyl oleate in the absence of air above
      50 degrees C. Two radical species are formed: the first one, stable up to
      approximately 110 degrees C, is an hydroxy-phenoxy radical whose ESR spectrum was
      analyzed by studying its temperature dependence and its sensitivity to
      deuterium/proton exchange. The second species was observed above 110 degrees C,
      its ESR spectrum was identical to the spectrum obtained when carnosol, another
      antioxidant extracted from rosemary, was heated at the same temperature in the
      presence of oxidized lipid. This observation is probably due to the
      transformation of carnosic acid into carnosol; the analysis of the corresponding
      ESR spectrum suggests the formation of a keto phenoxy radical exhibiting a great
      delocalization of the unpaired electron.

PMID- 7827697
TI  - [The mechanisms of the teratogenic action of alcohol].
AB  - Under study was the influence of different doses and methods of administration of
      ethanol on embryogenesis of rats and the effect of some shifts in homeostasis of
      a female rat on a manifestation of teratogenic effect of ethanol. Embryogenesis
      of rats is resistant to action of ethanol and acetaldehyde. Shift in the acid
      base balance to the acid side is not thought to be determining in the mechanism
      of the appearance of the fetal alcohol syndrome, while the embryotoxic effect of
      ethanol manifests itself against the background of an iron-deficient state of the
      maternal organism.

PMID- 7827698
TI  - [The forms and methods of controlling and evaluating the knowledge of medical
      institute students in anatomy, histology and topographic anatomy].

PMID- 7827699
TI  - [The collection of wax anatomical preparations in the Museum of the Department of
      Normal Anatomy of the Military Medical Academy].

PMID- 7827700
TI  - [The protein component of the epitheliocyte biopolymers in the small intestine
      after experimental vagotomy].
AB  - A histochemical investigation of biopolymers of the small intestine
      epitheliocytes after experimental vagotomy has shown that at early stages of the
      neurodystrophic process the most pronounced changes are noted in the distribution
      of amino acid residues of the proteins in the cytoplasm of epitheliocytes and in
      the composition of the glycoprotein secretion of goblet exocrinocytes. The
      undulatory changes might be accounted for by activation of the function of
      cholinergic nerve fibers coming via the sympathetic nerves against the background
      of vagus denervation. The changes in protein-containing biopolymers suggest deep
      disturbances in conditions of denervation. The primary changes might be a result
      of posttranslational transformations of the biopolymer complex molecules, while
      the later ones is a disturbance of the process of biosynthetic activity of the
      cells. It can't be excluded that the changes found might be a cause of
      postvagotomy diarrhea, often complicating the postoperative period in ulcer
      patients.

PMID- 7827701
TI  - [The regional morphological characteristics of the endothelium of the human
      thoracic aorta in perfusion fixation].
AB  - The ultramicroscopic organization and the endotheliocyte surface relief in
      ventral portions of the thoracic part of human aorta and in zones of division of
      blood flow were studied under conditions of early post mortem examinations and
      perfusion fixation of corpses of 14 humans dead from accidental causes. Zones of
      entrance into the intercostal aortas are compared with the straight portions of
      the aorta and are found to be characterized, as compared with the latters, by
      polymorphism of the endothelium, higher adhesiveness of its surface to blood
      elements, as well as by the presence of intravitally de-endothelialized portions
      localized on the ridge of the intimal valve.

PMID- 7827702
TI  - Treating asthma in adults.

PMID- 7827703
TI  - RNS president's message: The healthcare revolution.

PMID- 7827704
TI  - The effect of cold air on asthmatic patients.

PMID- 7827705
TI  - Making home health referrals for respiratory patients.

PMID- 7827706
TI  - Diane Leonard, RN.

PMID- 7827707
TI  - On the role of thalamic pathology in diencephalic amnesia.
AB  - Although it is now accepted that medial diencephalic lesions can produce severe
      amnesia in humans, the specific nuclei and neural pathways that must be damaged
      to impair memory have not yet been identified. Recent studies have shown that
      pyrithiamine-induced thiamine deficiency (PTD) in the rat can produce a
      consistent pattern of pathology in the thalamus and mammillary bodies and result
      in permanent impairments on behavioral measures of working memory. Behavioral
      deficits comparable to the PTD model have been observed in rats with thalamic
      lesions involving lateral portions of the internal medullary lamina (the L-IML
      site). Such impairments are not observed following lesions of limbic-related
      pathways associated with the fornix, mammillary bodies, or midline thalamus. The
      L-IML lesion affects the mediodorsal nucleus (MDn) and both the intralaminar and
      paralaminar non-specific thalamic nuclei. The relationship between the non
      specific thalamic nuclei and working memory is underscored by the limited
      behavioral effects of MDn lesions, as compared to either L-IML or PTD-induced
      lesions, and by anatomical analyses of PTD-related pathology, which seems to
      destroy the non-specific nuclei while sparing large portions of the MDn. Recent
      physiological studies of thalamocortical processes suggest that there are several
      possible mechanisms by which the non-specific nuclei might participate in memory
      and by which lesions in these pathways might interfere with the consolidation of
      memories within the cortex.

PMID- 7827708
TI  - Quantal analysis of hippocampal long-term potentiation.
AB  - Long-term potentiation (LTP) is a lasting (hours, days) increase in electrical
      responses after brief (seconds) high-frequency activation of monosynaptic
      pathways. It represents a popular model to study mechanisms of learning and
      memory. There is a general agreement on mechanisms of LTP induction, at least for
      LTP in hippocampal area CA1. However, a controversy exists about mechanisms of
      LTP maintenance: there is evidence for both pre- and postsynaptic locations of
      LTP mechanisms. Publications on statistical (quantal) analysis of fluctuations of
      excitatory postsynaptic potentials in hippocampal and some other structures are
      reviewed. The analysis suggests two independent mechanisms for LTP maintenance
      during the first hour. They are termed LTPm and LTPv and are expressed as changes
      in the mean number of transmitter quanta or quantal content (m) and changes in
      the effect of one quantum or quantal size (v), respectively. The increased number
      of transmitter quanta per presynaptic impulse (LTPm) can account for the many
      fold increase in synaptic efficacy during LTP, especially when initially "silent"
      connections increase their release probabilities (p). The increase in the number
      of effective release sites is considered to be secondary to the increase in p.
      Appearance of new subsynaptic receptors, which can produce an apparent increase
      in m, is not excluded. The additional mechanism (LTPv) can account for an
      essential part of potentiation when the LTP magnitude is relatively small (< 60%
      increase over pretetanic amplitude). Experiments with paired-pulse facilitation
      support postsynaptic mechanisms for quantization and for LTPv. Intriguing
      problems for future statistical analysis of quantal synaptic mechanisms for
      behavioral memory and conditioning are understanding the different mechanisms for
      induction of LTPm and LTPv, and their contribution to the maintenance of LTP
      during post-tetanic periods of > 1 hour.

PMID- 7827709
TI  - Pitfalls in assessment of c-fos mRNA expression in the brain: effects of animal
      handling.
AB  - Immediate early genes are rapidly and transiently induced by many stimuli and
      produce their transcription factors. Of the immediate early genes, the proto
      oncogene c-fos and its product Fos play a role in cell proliferation,
      differentiation and general signal transmission as the 'third messenger'
      regulating the transcription of other genes. Even minute stimuli such as the
      attachment of electrodes, needle injection and saline administration increase the
      level of c-fos mRNA expression in animal brains. It is, therefore, necessary to
      investigate the effects of using anesthetics and solvents for drug administration
      on c-fos expression in order to accurately assess net c-fos induction after
      stimulation. Furthermore, experimental procedures might themselves affect c-fos
      mRNA expression in the brain after in vivo stimulation. In this review, we
      discuss technical pitfalls in assessing in vivo c-fos expression. Rough handling
      with repeated saline administration enhanced cortical c-fos mRNA expression in
      the rat brain after a single saline injection by increasing baseline c-fos mRNA
      levels. In contrast, gentle handling with repeated saline administration
      diminished c-fos mRNA expression after a single injection by decreasing baseline
      c-fos mRNA levels. These two types of handling with the repeated injection led to
      diametrically opposite results on c-fos mRNA expression after a single
      stimulation. Our results suggest that c-fos mRNA induction after a single
      stimulation might be affected by the types or intensities of animal handling and
      that effects of animal handling must be considered when estimating c-fos mRNA
      induction.

PMID- 7827710
TI  - Effects of nerve growth factor in primate models of neurodegeneration: potential
      relevance in clinical neurology.

PMID- 7827711
TI  - A prospective randomized comparison of defibrillation efficacy of truncated
      pulses and damped sine wave pulses in humans.
AB  - INTRODUCTION: Damped sine wave pulses have been used for nearly 50 years in
      transthoracic defibrillation systems. The purpose of this study was to determine
      whether damped sine wave pulses have a role in implantable defibrillators.
      METHODS AND RESULTS: In 21 survivors of cardiac arrest, we prospectively compared
      defibrillation efficacy of a standard truncated capacitor (RC) monophasic pulse
      with a damped sine wave inductor-capacitor (LRC) pulse using a right ventricular
      left ventricular epicardial patch-patch electrode system. The RC pulse was a
      standard 65% tilt monophasic waveform generated from a 120 mu F capacitor. The
      LRC pulse was designed to simulate the waveform currently used in transthoracic
      defibrillators and was generated by passing the charge stored on a 40 mu F
      capacitor through a 37-mH inductor. Capacitor voltage, peak delivered voltage,
      peak delivered current, discharge pathway resistance, delivered energy, and
      stored energy were compared for the two waveforms at the defibrillation
      threshold. There was no difference in defibrillation efficacy for the two
      waveforms. Peak delivered voltage was similar at the defibrillation threshold:
      313 +/- 101 V for the RC pulse and 342 +/- 119 V for the LRC pulse (P = 0.16).
      Similarly, no differences were found in defibrillation threshold peak delivered
      current: 8.6 +/- 2.5 (RC) versus 9.3 +/- 2.7 (LRC) amperes (A) (P = 0.20);
      discharge pathway resistance: 37 +/- 11 (RC) versus 38 +/- 13 (LRC) omega (P =
      0.71); delivered energy: 7.0 +/- 4.5 (RC) versus 7.0 +/- 4.0 (LRC) joules (J) (P
      = 0.88); and stored energy: 8.7 +/- 5.7 (RC) versus 9.8 +/- 5.4 (LRC) J (P =
      0.35). Although both waveforms performed the same, it was necessary to use
      substantially higher stored voltages with the damped sine wave delivery system
      than with the truncated waveform delivery system: 356 +/- 110 V for the RC pulse
      and 675 +/- 192 V for the LRC pulse (P < 0.0001). CONCLUSION: This study
      demonstrates that RC monophasic pulses provide equally effective epicardial
      defibrillation as LRC pulses with respect to delivered voltage and current and
      stored and delivered energy. However, in order for LRC pulses to provide
      comparable delivered voltage, current, and energy to that of RC pulses, nearly
      twice the voltage must be stored on the capacitor to accomplish the same task.
      These findings suggest that despite the nearly 50-year experience with damped
      sine wave pulses with transthoracic defibrillators, there is no need to begin
      using damped sine wave pulses for implantable defibrillators. Moreover, these
      data raise a question regarding the need for inductors in transthoracic
      defibrillators.

PMID- 7827712
TI  - Mechanism-specific antiarrhythmic effects of the potassium channel activator
      levcromakalim against repolarization-dependent tachycardias.
AB  - INTRODUCTION: The hypothesis that levcromakalim, a potassium channel (IK-ATP)
      activator with antihypertensive properties, has a mechanism-specific
      antiarrhythmic action against repolarization-dependent ventricular tachycardias
      (VTs) was tested in dogs. METHODS AND RESULTS: A low dose of levcromakalim (0.01
      mg/kg) was selected, which decreased blood pressure by 25% but had almost no
      electrophysiologic effect on AV nodal or ventricular conduction or effective
      refractory period. In dogs with chronic AV block, the antiarrhythmic action of
      this dose of levcromakalim was evaluated in three models of abnormal impulse
      formation: (1) d-sotalol (2 mg/kg) induced torsades de pointes VT, initiated by
      early afterdepolarizations (EADs), (2) sustained ouabain-induced VTs, which are
      dependent on delayed afterdepolarizations (DADs), and (3) VT occurring 24 hours
      after left anterior descending coronary artery occlusion, which are likely based
      on abnormal automaticity. Levcromakalim abolished d-sotalol induced U waves,
      ventricular ectopic beats, and self-terminating bouts of torsades de pointes.
      Induction of torsades de pointes by pacing was also completely prevented. The
      cycle length of the idioventricular rhythm, which was lengthened after d-sotalol
      from 1490 +/- 515 to 1700 +/- 610 msec (P < 0.05), remained similar after
      levcromakalim (1655 +/- 580 msec). The QT(U) duration, which was increased after
      d-sotalol from 410 +/- 55 to 550 +/- 40 msec (P < 0.05), normalized to 405 +/- 70
      msec (P < 0.05). Levcromakalim did not suppress but rather enhanced ouabain
      induced VT by decreasing the cycle length slightly from 315 +/- 35 to 290 +/- 35
      msec (P < 0.05). Pretreatment with a beta blocker prevented this acceleration in
      rate. Finally, levcromakalim had no effect on VT 24 hours after infarction.
      CONCLUSION: A low dose of levcromakalim has specific antiarrhythmic properties
      against repolarization-dependent arrhythmias, but it does not affect VTs based on
      other mechanisms of abnormal impulse formation.

PMID- 7827713
TI  - Radiofrequency catheter ablation in unusual mechanisms of atrial fibrillation:
      report of three cases.
AB  - INTRODUCTION: The purpose of this study was to test the feasibility of
      radiofrequency (RF) catheter ablation of localized mechanisms of atrial
      fibrillation (AF). METHODS AND RESULTS: Three patients underwent RF catheter
      ablation for drug-resistant atrial arrhythmias. The first two patients had either
      incessant atrial tachycardia or AF. In the first patient, the ECG pattern of AF
      was mimicked by a very rapid atrial focus, whereas in the second patient, AF was
      due to true degeneration of the atrial activity triggered by atrial tachycardia.
      In both patients, the ablation of atrial focus led to the clinical disappearance
      of AF. The third patient had frequent episodes of AF, which lasted several days
      or weeks, and two documented episodes of atrial flutter. Mapping during AF showed
      an irregular atrial rhythm in the atrial septum, particularly in the region
      surrounding the coronary sinus, whereas the entire lateral right atrial free wall
      exhibited a constantly organized rhythm. RF energy was applied between the
      tricuspid ring and both the inferior vena cava and the coronary sinus, resulting
      in inability to reinduce atrial flutter or sustained AF. A 6-month follow-up in
      this patient showed the disappearance of prolonged episodes of AF. CONCLUSION:
      The observations indicate that AF may be linked to "focal" mechanisms that can be
      treated by RF catheter ablation.

PMID- 7827714
TI  - Effects of procainamide and lidocaine on defibrillation energy requirements in
      patients receiving implantable cardioverter defibrillator devices.
AB  - INTRODUCTION: In acute canine studies, lidocaine, but not procainamide, increases
      defibrillation energy requirements. We evaluated the effects of lidocaine or
      procainamide on defibrillation energy requirements in 27 patients undergoing
      intraoperative testing for implantable cardioverter defibrillator device
      placement. METHODS AND RESULTS: Patients were tested off antiarrhythmic drugs and
      again following either lidocaine (200 to 250 mg loading and 3 mg/min maintenance
      infusions) or procainamide (1 gm loading and 3 to 4 mg/min maintenance
      infusions). The defibrillation testing protocol consisted of initial testing at
      15 J, followed by higher or lower energies to determine the lowest energy
      producing three consecutive successful defibrillations. Overall, the mean
      defibrillation energy increased from 14 +/- 5 J to 18 +/- 7 J during lidocaine
      (plasma concentration 5.1 +/- 1.6 micrograms/mL; P < 0.02) but were similar at
      baseline (12 +/- 5 J) and during procainamide infusion (13 +/- 6 J) (plasma
      concentration: procainamide 10.7 +/- 7.2 micrograms/mL; N-acetyl procainamide 1.0
      +/- 0.4 micrograms/mL). A positive linear correlation was found between lidocaine
      plasma concentration and percent change in defibrillation energy (lidocaine: r =
      0.61; P = 0.01). Procainamide raised the defibrillation energy in three patients,
      two with supratherapeutic plasma concentrations. The increase in defibrillation
      energy equaled or exceeded 25 J in four patients after lidocaine and in one
      patient after procainamide. CONCLUSION: The data suggest that at high plasma
      concentrations, lidocaine and procainamide adversely affect defibrillation energy
      requirements consistent with an adverse, concentration-dependent effect of sodium
      channel blockade on defibrillation energy requirements in patients.

PMID- 7827715
TI  - Double-pulse defibrillation using pulse separation based on the fibrillation
      cycle length.
AB  - INTRODUCTION: We investigated a method of defibrillation in which two shocks were
      delivered to the same electrodes with a separation based on the cycle length of
      the fibrillation event (FCL). METHODS AND RESULTS: In pentobarbital anesthetized
      dogs, a computerized system determined the FCL from the fibrillation event,
      computed the desired double-pulse (DP) shock separation, and immediately
      delivered the DP shocks. In group 1, energy for 50% success at defibrillation
      (E50) was measured using separations from 55% to 95% of the FCL and remeasured
      after administration of flecainide, clofilium, or vehicle to change the FCL. Both
      drugs increased FCL by approximately 25%. Plots of E50 versus %FCL aligned before
      and after drug showed that the optimum pulse separation followed the FCL. In
      group 2, E50s were measured for 55% to 185% FCL separations in clofilium or
      vehicle-treated animals. The optimum DP E50 was at 85% FCL and was not
      significantly different from the single-shock E50. In group 3, no differences
      were found when comparing the probability of success versus total energy
      relationships for single and optimum DP shocks. Group 4 compared E50s for single
      and DP shocks using a single-catheter configuration and three-electrode
      configurations (catheter-subdermal patch). E50s for single and DP shocks were
      equal using the single-catheter configuration but DP shocks required
      approximately 20% more energy in the three-electrode configurations. CONCLUSION:
      In single-pathway lead configurations, two shocks with 85% FCL separation can be
      reliably combined to defibrillate using the same total energy as a larger single
      shock. Since the energy is unchanged but the total duration is doubled, DP shock
      currents are reduced by 20% to 30%.

PMID- 7827716
TI  - Smaller capacitors improve the biphasic waveform.
AB  - INTRODUCTION: Current implantable cardioverter defibrillators (ICDs) use
      relatively large capacitance values. Theoretical considerations suggest, however,
      that improved defibrillation energy requirements may be obtained with smaller
      capacitance values. METHODS AND RESULTS: We compared the energy requirement for
      defibrillation in a porcine model using a biphasic waveform generated from two
      capacitance values of 140 microF and 85 microF. Phase 1 reversal of the shock
      waveform occurred at 65% tilt. Phase 2 pulse width was equal to phase 1. Shocks
      were delivered through epicardial patch electrodes after 10 seconds of induced
      ventricular fibrillation. The defibrillation threshold (DFT) was determined by a
      "down-up" technique requiring three reversals of defibrillation success or
      failure. The DFT was defined as the average of the values obtained with all
      trials starting from the successful shock prior to the first failure to
      defibrillate to the last successful defibrillation. In eight experiments, the
      measured parameters at DFT were as follows. The average stored and delivered DFT
      energies for the 85 microF capacitor were 6.1 +/- 2.1 and 6.0 +/- 2.0 J,
      respectively, compared to 7.5 +/- 1.3 and 7.4 +/- 1.3 J for the 140 microF
      capacitor (P < 0.04). The phase 1 pulse widths were significantly shorter for the
      85 microF capacitor (5.1 +/- 0.8 msec vs 9.2 +/- 1.3 msec) and the impedances
      were lower (54.4 +/- 5.8 omega vs 59.9 +/- 6.3 omega). The mean leading edge
      voltage was trending higher for the 85 microF capacitor, but this difference did
      not reach statistical significance (374 +/- 63 V vs 326 +/- 30 V; P = 0.055).
      CONCLUSION: Smaller capacitance values do result in lower energy requirements for
      the biphasic waveform, at a possibly higher leading edge voltage and a much
      shorter pulse width. Smaller capacitance values could represent a significant
      enhancement of well-established benefits demonstrated with the biphasic waveform.

PMID- 7827717
TI  - Spontaneous incessant AV reentrant tachycardia related to left bundle branch
      block and concealed left-sided accessory AV pathway.
AB  - Three patients in whom permanent AV reentrant tachycardia became the clinical
      manifestation of Wolff-Parkinson-White syndrome are described. The substrate for
      the arrhythmia was created by coexistence of a concealed left-sided accessory
      pathway and an ipsilateral bundle branch block. Pharmacologic therapy in all
      three patients failed to control the tachycardia, which in two cases led to
      severe left ventricular failure. After successful radiofrequency ablation of the
      accessory pathway (in two) or AV junction (in one), left ventricular function
      gradually returned to normal.

PMID- 7827718
TI  - Independent ablation of retrograde and anterograde accessory connection
      conduction at the atrial and ventricular insertion sites: evidence supporting the
      impedance mismatch hypothesis for unidirectional block.
AB  - INTRODUCTION: The impedance mismatch hypothesis has been proposed as one of the
      mechanisms responsible for accessory connection conduction block. METHODS AND
      RESULTS: We describe a case in which retrograde conduction across a posteroseptal
      accessory connection was ablated at the atrial insertion site in the coronary
      sinus os, whereas anterograde conduction was ablated at the ventricular insertion
      site in the left ventricle. CONCLUSION: The evidence supports the impedance
      mismatch concept as the cause of unidirectional conduction block and shows that
      the distal junction between the accessory connection and the myocardium is more
      vulnerable to ablation.

PMID- 7827719
TI  - Radiofrequency catheter ablation of sustained intraatrial reentrant tachycardia
      in a patient with mirror-image dextrocardia.
AB  - INTRODUCTION: There has been limited experience with radiofrequency catheter
      ablation in patients with dextrocardia. This report describes a 37-year-old man
      who had secundum type atrial septal defect, mirror-image dextrocardia, and drug
      refractory atrial tachycardia, in whom catheter-mediated radiofrequency energy
      successfully eliminated the tachycardia without complication. METHODS AND
      RESULTS: On electrophysiologic study, the atrial tachycardia could be induced and
      terminated by atrial extrastimulation or rapid atrial pacing. Mixed resetting
      response pattern and manifest entrainment were also demonstrated. These findings
      suggested that the mechanism of atrial tachycardia might be related to reentry
      with an excitable gap. Because of the mirror-image dextrocardia, biplane
      fluoroscopy was adjusted to the right anterior oblique (RAO) 60 degrees and left
      anterior oblique (LAO) 30 degrees positions. Inducibility of the tachycardia was
      completely abolished after the sixth application of radiofrequency current (30
      W). It was noted that the successful electrogram preceded the onset of P wave
      during atrial tachycardia by about 40 msec. CONCLUSION: This report presents
      another case in which radiofrequency catheter ablation was used in a patient with
      dextrocardia. Atrial tachycardia in patients with congenital heart disease may be
      difficult to control pharmacologically; however, the use of radiofrequency
      catheter ablation could be recommended as an alternative to medication and
      surgery.

PMID- 7827720
TI  - Keep your lollipops!

PMID- 7827721
TI  - R.N.s beware! Healthcare "reform" may give your job to a tech!

PMID- 7827723
TI  - Quantumleap! Registered nurse-researchers blaze trails in unchartered
      territories.

PMID- 7827722
TI  - Image, practice and empowerment: a call to new leadership for the invisible
      profession.

PMID- 7827724
TI  - The rise and fall of good intentions.

PMID- 7827725
TI  - Defining nursing excellence.

PMID- 7827726
TI  - The student management team: a vehicle for empowerment.

PMID- 7827727
TI  - Revolution follows the breast cancer epidemic. Estrogen revisited.

PMID- 7827728
TI  - The tribe nurse and the scepter of power.

PMID- 7827729
TI  - Empower yourself against depression.

PMID- 7827730
TI  - Thank you, Ralph!

PMID- 7827731
TI  - White water rafting. "Incredible!".

PMID- 7827732
TI  - Rape, mugging, assault--dangers to nurses on the job.

PMID- 7827733
TI  - Humor and nursing? You've got to be kidding!

PMID- 7827734
TI  - A vision of professional nursing in 2020.

PMID- 7827735
TI  - Frank Poliafico, R.N.: fate and self-confidence. A winning combination. Interview
      by Rosemary O'Donnell.

PMID- 7827736
TI  - Nurse week--the annual put-down of R.N.s.

PMID- 7827737
TI  - National pressure ulcer prevalence survey.
AB  - In the 1993 survey, the prevalence of pressure ulcers was 11.1% in 177 hospitals.
      This is higher than the 9.2 prevalence rate Meehan found in 1989. The sacrum,
      with 38% (n = 2,168) of all reported ulcers, remains the most common site for
      pressure ulcer occurrence. Non-reactive hyperemia sites, Stage I, were
      responsible for most reported ulcers, at 46.95% (n = 2,839), while Stage II
      ulcers comprised 32.66% (n = 1,975). Patients between the ages of 70 and 89 years
      of age had 54% of the ulcers found. The average number of ulcers per patient was
      1.73. Dark-skinned, African-American patients again were found to have the
      majority of Stage IV ulcers. There were 1,024 ulcers reported in this stage
      group, and of these, they had 16% (n = 164). Of patients with ulcers, 22% were on
      some form of air or foam overlay support system; however, standard mattresses and
      mattress replacements were used for 31% of all patients with pressure ulcers.

PMID- 7827738
TI  - The lived experience of wives caring for their frail, homebound, elderly husbands
      with pressure ulcers.
AB  - The purpose of this study was to describe and to gain understanding for the
      unexplored experience of wives caring for their frail, homebound, elderly
      husbands with pressure ulcers. Using Spiegelberg's (1975) phenomenological
      method, the caregiving experience of six elderly women was explored. Five major
      themes were identified in this study: 1. difficult caregiving, which was further
      delineated into the physical, emotional, safety, and financial realms 2. frailty
      of the caregiver 3. limited socialization 4. limited social support systems 5.
      limited caregiving knowledge. The two minor recurring themes were (1) fear
      regarding the future, and (2) symbolic meaning of the pressure ulcer. From these
      themes implications for nursing practice, healthcare clinicians' education,
      healthcare policy reforms, and recommendations for future research emerged.

PMID- 7827739
TI  - Nutrition and air-fluidized beds: a literature review.
AB  - This is a review of the literature on air-fluidized beds and nutrition with an
      emphasis on patients with pressure ulcers. Studies suggest that the warm, dry
      environment of the air-fluidized bed may affect nutritional status. Patients
      maintained on air-fluidized beds have increased fluid losses and decreased
      urinary nitrogen losses. While the evidence suggests that air-fluidized beds may
      reduce protein catabolism, further and lengthier metabolic studies are needed.
      Clinicians should continue to provide high levels of energy and protein for
      patients with pressure ulcers on air-fluidized beds.

PMID- 7827740
TI  - High-touch in a high-tech world.

PMID- 7827741
TI  - Essay on knowledge, caring, and psychological factors in prevention and treatment
      of pressure ulcers.
AB  - The prevention and treatment of pressure ulcers can be assisted by assessing the
      knowledge and caring of caregivers as well as by assessing the risk of patients.
      When assessing patients with pressure ulcers, it is perhaps as important to
      assess psychological factors and support systems as it is to assess the usual
      physical factors. Dividing patients into a passive pressure ulcer group and an
      active pressure ulcer group leads to better quality of treatment outcomes.

PMID- 7827742
TI  - Response to Mikols' questions about changes in capillary pressure.

PMID- 7827743
TI  - Small-celled mattresses.

PMID- 7827744
TI  - Intermittent pneumatic compression improves venous ulcer healing.
AB  - The effects of intermittent pneumatic compression on the healing rates of ulcers
      in patients with chronic venous insufficiency were examined in a prospective,
      controlled study of 22 patients. Patients were randomly assigned to the
      experimental or the control group. Both groups received local wound care followed
      by application of an Unna boot. In addition, subjects in the experimental group
      received intermittent pneumatic compression (IPC) twice weekly for one hour each
      session. Healing rates were reported in square centimeters per day. Data analysis
      revealed a mean healing rate of 0.08 cm2 per day for control subjects and 0.15
      cm2 per day for experimental subjects. Statistical analysis, demonstrated the
      healing rates of the two groups to be statistically different. The results appear
      to indicate that intermittent pneumatic compression is beneficial in the
      management of venous insufficiency ulcers.

PMID- 7827745
TI  - Pressure-reducing effects of heel protectors.
AB  - This study examined the pressure-reducing effects of 13 different heel-protecting
      devices. A group of 40 elderly patients (mean age 82 years, range 71-94) admitted
      to the Geriatric Department of the University Hospitals in Leuven, Belgium
      participated in this study. The pressures were registered by means of a sensitive
      computerized diagnostic system, which measured vertical forces. An ordinary head
      pillow was shown to be the most effective pressure-reducing device, followed by
      heel protectors based on siliconized hollow fibers.

PMID- 7827746
TI  - Pressure-reducing capability of Conforma II mattress overlay.
AB  - Pressure readings over the sacral and trochanter areas were obtained on 30
      healthy adult volunteers. An anatomically contoured mattress overlay (Conforma
      II) was compared to a standard hospital mattress. The difference in the mean
      pressures over the sacral areas represented a 52% reduction in pressure, whereas,
      a 46% pressure reduction was obtained over the trochanter area. Body weight was
      significantly associated with higher mean pressures.

PMID- 7827747
TI  - The Neuman Systems Model as applied to the terminally ill client with pressure
      ulcers.
AB  - Nursing practice can be enhanced by using a systems approach to the client with
      multifaceted health problems. The Neuman Systems Model, based on the conceptual
      framework of stress and reaction to stressors, provides a framework for
      organizing a holistic approach to the nursing care needs of the terminally ill
      client with pressure ulcers.

PMID- 7827748
TI  - Support surfaces.

PMID- 7827749
TI  - The laminins.
AB  - Laminins are extracellular matrix proteins which consist of alpha, beta and gamma
      chains with molecular masses of 140-400 kDa. Chain association occurs through a
      large triple alpha-helical coiled-coil domain towards the C-terminus of each
      chain. Eight genetically distinct laminin chains (alpha 1, alpha 2, alpha 3, beta
      1, beta 2, beta 3, gamma 1, gamma 2) and seven different assembly forms (laminins
      1 to -7) are known so far. The most extensively characterized laminin-1 (alpha 1
      beta 1 gamma 1) shows calcium-dependent self assembly and heterotypic binding to
      perlecan, nidogen, fibulin-1 and other matrix components. This binding indicates
      a crucial role in the supramolecular organization of basement membranes. Laminins
      also possess binding sites for at least six different integrin receptors and are
      thus involved in many cell-matrix interactions. Such interactions have been shown
      to be important during embryonic development and for tissue homeostasis and
      remodelling.

PMID- 7827750
TI  - Glycosaminoglycan and collagen fibrillar interactions in the mouse corneal
      stroma.
AB  - When sections of mouse corneal stroma were treated with 20 mM adenosine 5'
      triphosphate (ATP) in phosphate buffered saline, pH 4.0, at 37 degrees C and
      observed by electron microscopy, numerous periodic fibrils with about 100-nm
      periodicity appeared which were the aggregated form of type VI collagen (type VI
      collagen fibrils). They occurred in close association with D-periodic fibrillar
      collagens (striated collagen fibrils). However, when the tissue was digested with
      chondroitinase ABC or testicular hyaluronidase prior to the ATP treatment, type
      IV collagen fibrils were segregated from striated collagen fibrils, even though
      the type VI collagen fibrils themselves aggregated to form the 100 nm-periodic
      structures. Keratanase or Streptomyces hyaluronidase had no such effect. One
      possible suggestion is that the ATP-aggregated type VI collagen fibrils are
      connected with striated collagen fibrils through chondroitin/dermatan sulfate
      glycosaminoglycans.

PMID- 7827751
TI  - Structure and stability of the triple-helical domains of human collagen XIV.
AB  - Two triple-helical domains, Col 1 and Col 2, were obtained from a pepsin digest
      of human placental collagen XIV and separated from each other under nondenaturing
      conditions. Edman degradation demonstrated 106 amino acids residues in the Col 1
      and 149 residues in the Col 2 domain. All except one of the 37 prolines in the
      Yaa position of the Gly-Xaa-Yaa triplets were completely hydroxylated to 4
      hydroxyproline, and there were three imperfections in the triplet repeat. Partial
      or complete hydroxylation and glycosylation were found for all seven lysines in
      the Yaa position. Domain Col 1 was joined by disulfide bonds into a trimer, while
      Col 2 appeared as a mixture of monomers and disulfide-linked dimers. Circular
      dichroic spectra were typical for the collagen triple helix and revealed
      relatively high melting temperatures for Col 1 (38 degrees C) and Col 2 (43
      degrees C). An almost perfect refolding of the triple helix was observed for Col
      1 but not for Col 2, emphasizing the importance of disulfide bonds for the
      folding kinetics and in part the stability of the triple helix. Circular dichroic
      spectra of the large nontriple helical domain, NC3, of collagen XIV indicated 11%
      alpha helix and 63% beta structure. Comparative melting profiles of NC3 and
      intact collagen XIV indicated that the triple helices in intact collagen XIV have
      a melting temperature of 44 degrees C.

PMID- 7827752
TI  - Molecular basis of nanomelia, a heritable chondrodystrophy of chicken.
AB  - Nanomelia is a recessively inherited connective tissue disorder of chicken
      affecting cartilage development. Other investigators have demonstrated that it
      involves low aggrecan production and diminished aggrecan mRNA levels. Based on
      genetic linkage studies showing a high likelihood that the mutation responsible
      for the nanomelic phenotype lay within the aggrecan gene, a series of experiments
      was performed to define the molecular basis of the trait. Aggrecan mRNA was
      present in the nucleus of the nanomelic chondrocyte but greatly reduced in the
      cytoplasmic compartment, a finding suggestive of a premature stop codon within
      the aggrecan transcript. Since no defect in mRNA splicing could be demonstrated
      by ribonucleasease protection studies, direct DNA sequencing was initiated by
      polymerase chain reaction of the mRNA and of genomic DNA. A stop codon was
      demonstrated at codon 1513, which is located in the eighth repeat of the
      chondroitin sulfate 2 domain of the large tenth exon. The mutation creates a
      unique BasBI restriction site which readily distinguishes the mutant and wild
      type alleles.

PMID- 7827753
TI  - Single-strand conformation polymorphism analysis of human decorin, biglycan and
      fibromodulin cDNAs.
AB  - The coding regions of the human decorin, biglycan and fibromodulin cDNAs have
      been examined utilizing the method of single-strand conformation polymorphism
      analysis. Analysis of total RNA from a group of eight human skin fibroblast cell
      lines did not detect any sequence variations in the decorin cDNA. In contrast,
      the analysis detected three sequence variations in the biglycan cDNA and one in
      the fibromodulin cDNA from the same group of cell lines. For the biglycan cDNA,
      one variation involved a position in the 5'-untranslated region, while the other
      two affected the wobble bases of triples encoding serine residues 10 and 143 of
      the mature core protein. For the fibromodulin cDNA, the variation involved the
      wobble position of the codon for glutamic acid residue 61 of the putative mature
      core protein. Single-strand conformation polymorphism analysis of these
      proteoglycan cDNAs was also applied to study patients exhibiting a variety of
      connective tissue pathologies, including chondrodysplasia punctata, Desbuquois
      syndrome, Dyggve-Melchior-Clausen syndrome, dyssegmental dysplasia, Ehlers-Danlos
      syndrome types I and III, Ellis van Creveld syndrome and thanatophoric dysplasia,
      though no additional sequence variations were detected.

PMID- 7827754
TI  - Cell-type specific promoters of the chick alpha 2(I) collagen gene in
      chondrocytes and fibroblasts.
AB  - Two different promoter regions responsible for the cell-type specific transcripts
      of the collagen alpha 2(I) gene in chick embryonic fibroblasts and chondrocytes
      are described. A region including part of intron 1 of the fibroblast alpha 2(I)
      gene is able to promote transcription in chondrocytes. This promoter region is
      located 5' to the chondrocyte-specific transcript, from -2205 to +42, relative to
      the chondrocyte transcription start site. When it is placed upstream of a
      luciferase reporter gene in transiently transfected chondrocytes, luciferase
      activity is stimulated 78-fold. The region between -2205 and -1298 is most
      important for the activity of the chondrocyte promoter, since a truncated
      promoter from -1298 through +42 gives only 15% as much activity. A similar low
      level of activity is given by the sequence -96 through +42. In transfected
      fibroblasts, a region from -1600 through +46, relative to the fibroblast
      transcription start site, stimulates transcription of a luciferase reporter gene
      by more than 1,000-fold. Deletions from -1185 through -807 and from -707 through 
      90 reduce promoter activity to 22% and 32%, respectively, of that given by the
      intact promoter. The chondrocyte and fibroblast promoters are each cell-type
      specific and are relatively inactive in the other cell type. Subregions within
      the fibroblast promoter, from -1154 through -1055, from -712 through -85, and the
      sequence containing the inverted CCAAT motif from -93 through -67, differentially
      bind factors in fibroblast but not chondrocyte nuclear extracts.

PMID- 7827755
TI  - Length variation in the keratan sulfate domain of mammalian aggrecan.
AB  - The keratan sulfate domain of aggrecan consists of a series of tandemly repeating
      hexapeptides which have the consensus sequence Glu-Glu/Lys-Pro-Phe-Pro-Ser, where
      the serine side-chains presumably provide sites for the attachment of keratan
      sulfate (KS) chains. The number of hexapeptide repeats varies between species,
      ranging from four in rat (Doege et al., 1987) and mouse (Walcz et al., 1992) to
      13 in human (Doege et al., 1991) and 23 in bovine aggrecan (Antonsson et al.,
      1989). Chicken aggrecan (Chandrasekaran and Tanzer, 1992) does not contain a KS
      domain with a recognizable hexapeptide motif. The extent of this variation among
      mammalian and avian species is not known, and there is currently no explanation
      to predict how differences in the size of the KS domain would affect aggrecan
      function. We used polymerase chain reaction (PCR) to amplify the portion of the
      human, canine and porcine aggrecan gene that codes for the KS domain. We
      sequenced the amplified products in each case. Human aggrecan, with 13
      hexapeptide repeats (Doege et al., 1987), was used as reference and found to be
      essentially identical to published data. The canine and porcine KS domains
      consisted of six and ten hexapeptide repeats respectively. The same PCR protocol
      was used to amplify the KS domain from genomic DNA of eight other mammalian
      species. Comparison of the size of these amplified products, as determined by
      agarose gel electrophoresis, with those for which sequence data are available
      allowed us to estimate the number of repeats in the KS domain. In almost half the
      species examined, the KS domain consisted of 13 hexapeptide repeats.

PMID- 7827756
TI  - Characterization of primary cultures of chondrocytes from type II collagen/beta
      galactosidase transgenic mice.
AB  - Studies on the function of extracellular matrix components of cartilages and on
      chondrocyte-specific regulatory mechanisms will benefit from approaches in which
      transgenic mice and cell cultures will complement each other. We therefore
      established and extensively characterized primary cultures of mouse chondrocytes
      isolated from rib growth plates of newborn mice harboring a transgene in which
      type II collagen gene regulatory sequences were driving expression of an E. coli
      beta-galactosidase reporter gene. Primary chondrocytes expressed a fully
      differentiated phenotype in monolayer culture, producing mRNAs for the collagen
      types II, IX and X, and for the transgene. Transgenic cells also synthesized high
      levels of E. coli beta-galactosidase, easily quantifiable and also detectable in
      individual cells by X-gal staining. When chondrocytes were isolated from
      transgenic mice in which beta-galactosidase was fused to the product of the
      neomycin resistance gene, they displayed resistance to G418. After one to two
      weeks in culture, chondrocytes progressively lost expression of the transgenes,
      in parallel with that of cartilage-specific genes, and started expressing high
      levels of type I collagen RNA. The use of transgenic chondrocytes allowed us to
      easily score phenotypic changes by assaying beta-galactosidase activity and
      neomycin resistance. Cultures of mouse chondrocytes, such as those reported here,
      should also help characterize biochemically the phenotypes of other transgenic
      mice in studies of genetic diseases of cartilages and of mechanisms involved in
      chondrogenesis.

PMID- 7827757
TI  - Ultrastructural studies of bones from patients with osteogenesis imperfecta.
AB  - Bone samples from patients suffering from osteogenesis imperfecta (OI) types I,
      II, III and IV, as well as normal controls, were studied by scanning (SEM) and
      transmission electron microscopy (TEM). SEM views of normal bone at low
      magnification show coherent structure, with regular striations due to a lamellar
      plywood-like arrangement of the mineralized collagen fibrils. Compact lamellar
      bone was also found in various OI specimens, but in limited disconnected regions
      separated by open spaces. Furthermore, some OI, but not normal, bones have
      regions of loose unconnected fibers and others of apparently abnormally dense
      mineral deposition. High resolution TEM studies of OI bone fragments have served
      to elucidate the structures of these different textures. There appears to be a
      substantial, though reduced, proportion of normal lamellar bone even in quite
      severe OI. However, the regions of loose fibers are largely unmineralized and
      probably contain abnormal collagen. Other regions are overmineralized, with
      generally small unorganized apatite crystals deposited onto fibril surfaces or in
      separate clusters. These structural abnormalities, together with the paucity of
      normal bone, may explain the fragility of OI bones.

PMID- 7827758
TI  - [Nasal ventilation in acute COLD].

PMID- 7827759
TI  - [Day hospitals: general or specialized?].

PMID- 7827760
TI  - [Evaluation of replacement therapy in emphysema caused by alpha 1-antitrypsin
      deficiency].
AB  - Assessment of alpha 1-antitrypsin replacement therapy (AAT) for emphysema.
      Patient characteristics were analyzed along with the possible side effects of the
      treatment and its efficacy in maintaining appropriate AAT blood levels. Lung
      function changes were also studied. The treatment protocol began with 4 weekly
      intravenous doses of 60 mg/kg AAT (Prolastin) and continued with monthly doses of
      240 mg/kg. AAT serum levels were measured before each dose. Every 6 months
      pulmonary function tests (spirometry, plethysmography and CO transfer) were
      performed. Thirteen patients (mean age 46 yr) have been studied since 1988. Mean
      initial FEV1 was 0.79 l. Over 250 doses have been infused with no significant
      side effects reported. AAT levels before treatment in 3 patients were lower than
      that considered protective (50 mg/dl). Function tests results indicated
      stabilization of spirometric values in most cases. Diagnosis of AAT deficiency is
      delayed considerably, meaning that significant functional deterioration takes
      place before replacement therapy begins. No side effects of treatment have been
      observed. Until an appropriate interval between doses has been established, each
      patient's AAT levels must be monitored.

PMID- 7827761
TI  - [Fiberoptic bronchoscope disinfection with glutaraldehyde phenolate in 1:8
      solution].
AB  - We evaluated the efficacy of phenolated glutaraldehyde in a 1:8 solution for the
      disinfection of bronchofibroscopes that were highly contaminated with Serratia
      marcescens and Pseudomonas aeruginosa. An Olympus BF-P10 bronchofibroscope was
      contaminated with artificial samples containing one of the aforementioned
      microorganisms in concentrations nearing 10(8) colony forming units per
      milliliter (cfu/ml). The instruments were then washed with soap and water and
      submerged in a 1:8 solution of phenolated glutaraldehyde. Samples were taken for
      culturing after contamination, after washing, and after 10, 15 and 30 min in the
      disinfectant solution. The level of cfu/ml in the cultures was measured and the
      definition of failure-to-disinfect was a finding of > or = 1 cfu/ml after each
      experimental procedure. Twenty procedures, 10 for each microorganism, were
      carried out. Washing of the bronchofibroscope afforded significant elimination of
      microorganisms and no colony growth was observed in cultures after 10 min
      submersion in phenolated glutaraldehyde. We conclude that immersion in a 1:8
      solution of phenolated glutaraldehyde after careful washing is a valid way to
      disinfect bronchofibroscopes that are highly contaminated with S. marcescens and
      P. aeruginosa.

PMID- 7827762
TI  - [Rapid surgical exploration of the mediastinum].
AB  - This study aimed to evaluate the morbidity-mortality of surgical exploration of
      the mediastinum in patients with mediastinal masses or adenopathy in the context
      of a rapid-surgery program that has been operating over the past 8 years (1985
      1993). A total of 93 mediastinal explorations have been carried out. Sixty-five
      involved transcervical mediastinoscopy, 20 were anterior mediastinotomies, 4 were
      combined procedures and 4 were video-thoracoscopies. We found 34 cases of
      lymphoma, 28 of metastasis of bronchopulmonary carcinoma and 16 of mediastinal
      ganglionic tuberculosis; the 15 remaining cases were classified as miscellaneous.
      No deaths were directly related to the surgical procedures; morbidity involved 2
      wound infections. Surgical exploration of the mediastinum is a safe diagnostic
      procedure, provided it is carried out by an experienced team, and allows care
      givers to take better advantage of therapeutic options with no loss of quality.

PMID- 7827763
TI  - [Contribution of the bronchodilator test in the study of bronchial
      reversibility].
AB  - This study sought to determine the optimum dose of salbutamol and the most useful
      method for calculating bronchodilator response. Changes in FEV1 after inhalation
      of 3 doses of salbutamol 200 micrograms were measured in 150 adults (64 healthy
      individuals, 18 with rhinitis, 53 with asthma and 15 with bronchitis).
      Bronchodilator response was calculated by 4 different methods: absolute value,
      percent change form baseline FEV1, from theoretical value and from weighted
      value. Significant differences in response were observed among the various
      methods of assessment. Patients with asthma and bronchitis showed the greatest
      response to salbutamol and their results were used to analyze the usefulness of
      the reversibility indices. The index that discriminated best was percent of
      theoretical reference value, although the sensitivity of this index was low and
      specificity varied from 0.73 to 1 depending on the cut-off point used. This index
      of reversibility along with absolute value proved to be the least dependent on
      baseline FEV1. We conclude that bronchodilator response is best assessed by
      calculating changes in FEV1 in relation to a theoretical reference value. This
      bronchomotor test, however, does not adequately assess patients with asthma and
      bronchitis.

PMID- 7827764
TI  - [Therapeutic strategy in venous thromboembolic disease (VTD)].

PMID- 7827765
TI  - [Respiratory diseases in Ancient Egypt].

PMID- 7827766
TI  - [Tracheobronchomegaly associated with light chain deposition disease].
AB  - Tracheobronchomegaly, also known as Mounier-Kuhn's Syndrome, is characterized by
      market dilation of the trachea and main bronchi and has been reported in
      association with several conditions, particularly connective tissue disease. The
      pathogenesis and clinical signs of light chain deposition disease are similar to
      those of light chain amyloidosis, in which these chains are deposited as
      amorphous material lacking the tinctorial features of the amyloid. We present a
      case involving both entities, an association that has not been previously
      reported, and we review the main characteristics of both diseases.

PMID- 7827767
TI  - [Primary sternal hemangiosarcoma].
AB  - We describe a 22-year-old man with a bone mass in the middle and lower third of
      the sternum with no signs of respiratory deterioration. After biopsy by incision
      established a diagnosis of hemangiosarcoma, appropriate resection and repair of
      the thoracic wall was scheduled. An adequate amount of tissue for analysis must
      be obtained to allow choice of a surgical technique that will assure the best
      prognosis in malignant tumors of the sternum and assignation of the most
      appropriate mechanical ventilation procedure.

PMID- 7827768
TI  - [Cystic adenoid carcinoma. Apropos of a case with very prolonged survival].
AB  - Adenoid cystic carcinoma is an infrequent tumor, but not a rare one. Its primary
      location is most often the salivary glands, although it can be found in many
      other organs, including the lung, which is the most frequent site of remote
      metastasis. The tumor's two main features, which indicate a need for long-term
      monitoring, are 1) its high level of local aggressivity and rate of recidivism in
      spite of radical excision, with recurrence sometimes taking place long after the
      primary tumor appears, and 2) its slow natural history even when disseminated
      disease is present. Type of tumoral tissue is an important prognostic factor.

PMID- 7827769
TI  - [Pulmonary thromboembolism and nephrotic syndrome: usefulness of magnetic
      resonance angiography].

PMID- 7827770
TI  - [Carboxyhemoglobin (COHb) concentration in nonsmokers living in an urban area].

PMID- 7827771
TI  - [Minimal intervention in the treatment of smoking].

PMID- 7827772
TI  - [Hypogonadotropic hypogonadism and gynecomastia as a form of manifestation of
      squamous carcinoma of the lung].

PMID- 7827773
TI  - [Rhodococcus equi pneumonia in patients with AIDS].

PMID- 7827774
TI  - Studies on small (< 300 microns) microcapsules: II--Parameters governing the
      production of alginate beads by high voltage electrostatic pulses.
AB  - The size of microcapsules is a critical parameter in the immunoisolation of
      islets of Langerhans by microencapsulation. The use of smaller capsules decreases
      the total implant volume and improves insulin kinetics and oxygen supply. A high
      voltage electrostatic pulse system was used for the production of small (< 300
      microns) alginate beads, the first step of the encapsulation technique. However,
      islets often protruded from capsules that were too small, further emphasizing the
      need for a method to control bead size. A study of 7 parameters [electrostatic
      pulse amplitude (A), duration (D) and wavelength (lambda), pump flow rate (P),
      needle gauge, alginate viscosity and distance between electrodes] showed that P
      (r = 0.981, p = 0.003) and lambda (r = 0.988, p = 0.0002) were the principal
      determinants of bead size. To detect potential interactions between parameters,
      270 combinations of different levels of A, D, lambda, and P were studied. A
      multivariate regression analysis of these data confirmed that P and lambda are
      the prime determinants of bead size, and showed that a 2-parameter (P, lambda)
      model could be used to precisely predict bead size (R2 = 0.84), while keeping the
      application simple. The precision of the predictive model is only slightly
      improved by the use of additional parameters. The reliability of the data used to
      elaborate this model was demonstrated (p = 0.6226) by comparing them with a
      second data set obtained under the same conditions. A third set of experiments
      confirmed the applicability of the model. This work has major implications on the
      preclinical application of microencapsulation since it showed that it is possible
      to predetermine the bead size.

PMID- 7827775
TI  - Hollow fibers for hepatocyte encapsulation and transplantation: studies of
      survival and function in rats.
AB  - In this study, the feasibility of transplanting hepatocytes using hollow fibers
      (HF) was investigated. Experiments were carried out in vitro and in vivo to
      determine the viability and function of hepatocytes encapsulated in four
      different types of commercially available HF: regenerated cellulose HF (RCHF),
      polysulfone HF of two different sizes (PSHF-1 and PSHF-2), and polyvinylidine HF
      (PVDF). Hepatocytes remained viable in all types of HF for at least 1 wk in vitro
      as measured by light microscopy and their ability to synthesize protein and
      secrete albumin. However, the levels of protein synthesis and albumin secretion
      in these cells varied significantly between different HF (RCHF > PSHF-2 > PVDF
      approximately PSHF-1) and appeared to be inversely related to their internal
      diameters (215, 500, 1000, and 1100 microns for RCHF, PSHF-2, PVDF, and PSHF-1,
      respectively). While PSHF-2, PVDF, and PSHF-1 did not support long term viability
      in vivo, hepatocytes in RCHF survived after implantation in the mesentery. After
      24 h in vivo, the hepatocytes appeared morphologically intact and exhibited a
      similar rate of protein synthesis when compared with cells cultured in parallel.
      The hepatocytes in RCHF also maintained the ability to synthesize protein after 7
      days in vivo. These results suggest that HF of appropriate size may be useful for
      hepatocyte transplantation applications in which prevascularization is not
      possible.

PMID- 7827776
TI  - A new technique for isolating and culturing human hepatocytes from whole or split
      livers not used for transplantation.
AB  - Large numbers of human hepatocytes were obtained from split and whole livers by
      using an adaptive form of the collagenase perfusion technique employed in rodent
      and human biopsies. In order to guarantee a homogenous distribution of the
      perfusate within the whole specimen, major hepatic veins were cannulated with
      large bore catheters. This technique allowed for the isolation of human
      hepatocytes on a large scale (up to 18.5 x 10(9) in one case) from normal and
      diseased liver specimens. The yield of isolated normal viable hepatocytes is
      inversely proportional to the donor age. In addition, it was noted that a short
      time between declared death and organ harvest (cross clamp time) results in
      higher viability of hepatocytes. In contrast, the time of cold organ preservation
      did not correlate with the viability or the yield of isolated hepatocytes. We
      conclude that the technique presented here allows isolation of large numbers of
      human hepatocytes from specimens unsuitable for transplantation but very valuable
      for biomedical research.

PMID- 7827777
TI  - Carboxyfluorescein (CFSE) labelling of hepatocytes for short-term localization
      following intraportal transplantation.
AB  - Renewed interest in the transplantation of isolated hepatocytes into the liver as
      a potential therapy for liver disease has stimulated the development of methods
      for the identification of donor cells within the recipient organ. We describe a
      method for cellular tagging and in vivo identification of intraportally
      transplanted hepatocytes using an intracellular fluorescent dye, 5(6)
      carboxyfluorescein diacetate, succinimidyl-ester (CFSE). Rat and porcine
      hepatocytes were isolated and labelled with CFSE. The optimal conditions for
      labelling consisted of a buffered saline suspension of hepatocytes (5 x 10(6)
      cells/mL) in 20.0 microM CFSE incubated for 15 min at 37 degrees C. In vitro,
      labelled hepatocytes were cultured either on fibronectin-coated chamber slides or
      in culture flasks. Cultures were evaluated in situ by fluorescence
      photomicrography or by fluorescence-activated cell sorting (FACS) after cell
      detachment. Cell viability was assessed serially and cultured, labelled
      hepatocytes retained the dye for up to 3 wk (last day of study). CFSE did not
      effect hepatocyte viability and there was no evidence of intercellular diffusion
      of the dye. In vivo, syngeneic Lewis rats underwent selective portal vein
      infusion of freshly isolated, labelled hepatocytes (2.0 x 10(7) cells/2.0 mL
      saline/animal) into the posterior liver lobes. All recipients were sacrificed 48
      h and 96 h later and their livers examined. Transplanted hepatocytes were
      identified by fluorescence microscopy in tissue sections and by FACS following
      collagenase digestion of the liver tissue. CFSE persisted in a population of
      viable, engrafted hepatocytes. FACS analysis demonstrated that 9 +/- 3% of the
      hepatocytes in the posterior liver lobes were labelled 48 and 96 h after
      transplantation. At 96 h following transplantation, multiple engrafted
      hepatocytes could be observed by fluorescence microscopy around the central
      veins. CFSE labelling allows for both in vitro identification and in vivo
      localization of donor hepatocytes. Furthermore, it appears to be more stable and
      specific for labelling hepatocytes than other tested dyes (especially DiI).

PMID- 7827778
TI  - Hepatocellular transplantation into the lung in chronic liver failure following
      bile duct obstruction in the rat.
AB  - Injection of hepatocytes or cell-free supernatant into the lung was able to
      prevent death from surgically induced fulminant hepatic failure in the rat in
      over 90% and 53% of subjects, respectively. The aim of this study was to
      investigate whether this technique can be applied in chronic liver failure.
      Chronic liver failure was induced in Lewis rats by ligation and transection of
      the common bile duct, which led to cirrhosis after 3-5 wk in all animals. Four
      groups of animals were formed: group 1 (n = 5), normal rats, serving as control;
      group 2 (n = 15), cirrhotic rats, no further treatment; group 3 (n = 14),
      hepatocyte transplantation by injection of cell suspension transcutaneously into
      the right lung of cirrhotic animals four wk after bile duct ligation; group 4 (n
      = 17), injection of 1 mL cell-free supernatant intravenously at two-day
      intervals, starting 4 wk after ligation. Liver function tests, prothrombin time
      and serum protein levels were measured weekly before and every two days after
      transplantation. In group 2 all animals had died 56 (49-69) days after ligation.
      Survival in groups 3 and 4 was similar: all rats had died from liver failure 61
      (51-72) and 60 (49-76) days following bile duct ligation. Survival rates and
      laboratory investigations showed no significant differences between treated and
      untreated cirrhotic animals. These data suggest that hepatocyte transplantation
      into the lung as well as supernatant injection do not have any significant effect
      on chronic hepatic failure, at least in the rat model.

PMID- 7827779
TI  - Unrelated donor bone marrow transplants in children.
AB  - Only a small proportion of children who might benefit from bone marrow transplant
      (BMT) have an HLA-identical sibling. To provide this potentially curative therapy
      to patients without a matched related donor, marrow transplants using less well
      matched related donors or unrelated donors (identified through computerized donor
      registries) have been performed. We report the outcome of 24 consecutive
      unrelated donor BMT's performed on children. Eligible diagnosis included acute
      leukemia (AL) (n = 15), chronic myelogenous leukemia (CML) (n = 4),
      myelodysplastic syndrome (MDS) (n = 3), and severe aplastic anemia (SAA) (n = 2).
      All donor/recipient pairs were sero-matched at 5 or 6 of the 6 HLA A, B, and DR
      antigens. Several different preparative regimens were used, but fractionated
      total body irradiation (TBI) was used in 20 patients. All recipients received
      graft-versus-host-disease (GVHD) prophylaxis with cyclosporine-A (CSA), four with
      short course methotrexate (MTX), 14 in combination with short course MTX and
      methylprednisolone (MPS), and five in combination with a mouse monoclonal
      antibody to CD5, coupled to the A-chain of ricin (Xomazyme-65). One patient
      received CSA and MPS alone after a T-cell depleted marrow transplant. Twenty of
      23 evaluable recipients engrafted (87%). Two patients with CML never engrafted
      and had autologous marrow recovery, one patient with SAA died at 128 days without
      evidence of engraftment, and there was one early death at day + 9. Fourteen of 20
      patients (70%) with stable donor-derived hematopoiesis developed significant
      acute GVHD > or = grade II). Eleven of 15 engrafted patients who survived > 100
      days after BMT developed chronic GVHD (73%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7827780
TI  - Morphology and function of cultured human fetal pancreatic cells transplanted
      into athymic mice: a longitudinal study.
AB  - Islet-like cell clusters generated from human fetal pancreases between 18-24 wk
      gestation were able to grow and mature both morphologically and functionally
      after transplantation under the kidney capsule of athymic nude mice. Grafted
      tissue, predominantly ductal in appearance was unresponsive to glucose 2 wk after
      grafting. The tissue assumed the trabecular column-like architecture of adult
      islets by 3 mo, with a concomitant 3-4-fold increase in serum human C-peptide
      concentration after glucose challenge. Moreover, at that time the surface area of
      insulin containing cells in the graft increased 20-fold over the starting
      material. Exocrine components, identified by their characteristic eosinophilic
      secretory granules were also identified at this time. Transplanted cell clusters
      were capable of releasing C-peptide for at least 12 mo, when the experiment was
      terminated. At this time, 1 yr posttransplantation, although the proportion of
      insulin containing cells in the graft remained unchanged from that measured at 4
      mo, a reduction in the magnitude of the C-peptide response to glucose was
      observed; this finding coincided with a significant mononuclear infiltrate in
      some areas of the transplanted tissue. In summary, human fetal pancreatic cells
      grown in tissue culture as cell aggregates, after transplantation under the
      kidney capsule, remain functionally viable for virtually the life span of
      immunocompromised rodents. Because of their long-term viability, the use of islet
      like cell clusters is a potentially useful method to expand transplantable cells.

PMID- 7827781
TI  - Improved functional survival of human islets of Langerhans in three-dimensional
      matrix culture.
AB  - The current study evaluates functional survival of human islets maintained in
      tissue culture for up to 4 wk in suspension media (CMRL-1066 with supplements)
      and contrasts these results with immobilizing three-dimensional matrices (agarose
      or alginate). The absolute number and volume of islets retrieved from agarose is
      significantly higher after two and four wk of culture compared to conventional
      free-floating media. In vitro function of islets, assessed by insulin/DNA
      content, insulin secretion into the culture media over 24 h and glucose
      theophylline stimulated insulin release in a dynamic perifusion system, was not
      significantly different between free-floating and matrix preserved islets. In
      vivo islet function was evaluated by the effectiveness for reversal of insulin
      dependent diabetes mellitus by transplantation of the islets under the kidney
      capsule of nude mice. Although adequate insulin responses to glucose were seen
      after culture in conventional or matrix media, only agarose embedded islets were
      consistently able to induce normoglycemia in diabetic recipients after 14 days of
      culture. Additional transplantation experiments defined the threshold level
      required to reverse diabetes to be between 1,000 and 1,500 agarose preserved
      islets. Our data suggest improved engraftment of human islets after agarose
      culture. This culture method may be of benefit for the accumulation of
      functionally competent human islets, thus facilitating the implementation of
      clinical protocols that utilize freshly isolated islets from multiple donors
      without the need for cryopreservation.

PMID- 7827782
TI  - Single donor transplantation of fresh and cryopreserved pancreatic fragments into
      the liver parenchyma in syngeneic rats.
AB  - In a series of experiments on syngeneic rat islet (pancreatic fragments)
      transplantation we demonstrate that direct hepatic transplantation is successful
      to alleviate streptozotocin induced diabetes with tissue from a single donor. The
      experimental groups were: recipients of fresh, and cryopreserved pancreatic
      fragments. The fresh graft was prepared by collagenase digestion. Cryopreserved
      fragments were further treated by a standard freeze-thaw protocol which consists
      of slow cooling at 0.3 degrees C/min to -75 degrees C followed by transfer to 
      196 degrees C, in the presence of 1.4 M Me2SO, and storage at this temperature
      for one day or 1 wk, and then warming them back to room temperature at a rate of
      35 degrees C/min. Streptozotocin-induced diabetes in rats can be reversed by
      injection of isolated pancreatic fragments from a single donor directly into the
      liver. No significant difference was observed between the recipients receiving
      fresh or cryopreserved tissue for 1 day or 1 wk. It is possible that elaborate
      purification itself is not conducive to successful alleviation of diabetes. This
      would corroborate the hypothesis that trophic factors are present in impure
      fragments. The direct infusion of islet fragments into the liver could allow for
      percutaneous administration in human transplantation.

PMID- 7827783
TI  - Aberrant function and long-term survival of mouse beta cells exposed in vitro to
      high glucose concentrations.
AB  - In vitro culture of murine Langerhans islets usually ends in islet death after 1
      3 wk. Given contradictory published data, we studied the influence of glucose on
      the function and survival of islets from DBA/2 mice. Islets were cultured on
      plastic microwells, using 1, 2, or 11 g/l glucose concentrations. Using our
      routine technique, insulin secretion was evaluated after islet incubation for 15
      min in basal medium [(sIS), 1 g/l glucose], followed by 15 min in stimulating
      medium [(sIS), 3 g/l glucose, 20 mM/l arginine, 5 mM/l theoophylline]. Insulin
      secretion of islets cultured in 1 g/l glucose remained stable and normal over a
      period of 2 mo [Day 7: bIS, 6.3 +/- 3.1 microU/50 microliters; sIS, 16.6 +/- 6.8
      microU/50 microliters. Day 60: bIS, 6.0 +/- 4.0 microU/50 microliters; sIS, 21.3
      +/- 10.5 microU/50 microliters]. Islet morphology also remained normal. Islets
      cultured in 2 g/l glucose showed elevated insulin response under basal and
      stimulating conditions during 2-3 wk, followed by a dramatic drop in insulin
      secretion [Day 7: bIS, 19.5 +/- 5.7 microU/50 microliters; sIS, 80.9 +/- 10.7
      microU/50 microliters. Day 60: bIS, 5.4 +/- 5.0 microU/50 microliters; sIS, 2.7
      +/- 1.4 microU/50 microliters]. Severe morphologic alterations appeared rapidly
      and islet destruction was nearly complete by 60 days. At 11 g/l glucose,
      functional and morphological islet alterations were accelerated [Day 7: bIS, 10.3
      +/- 2.7 microU/50 microliters; sIS, 18.8 +/- 4.9 microU/50 microliters. Day 21:
      bIS and sIS almost undetectable].(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7827784
TI  - Promoting laboratory research during infectious diseases fellowship training or
      telling the truth about training in clinical research.

PMID- 7827785
TI  - Rabies--an historical perspective.

PMID- 7827786
TI  - Trypanosomatid protozoa provide paradigms of eukaryotic biology.
AB  - Over the last 10 years, trypanosomatid protozoa have been the subject of intense
      investigation particularly focusing on their parasitic lifestyle and their
      intriguing and novel cell properties. These studies have furthered our
      understanding of the physiology and functioning of these cells and have
      identified a large number of biochemical and metabolic peculiarities, including
      mitochondrial function, enzymatic compartmentalization, and gene expression. This
      review focuses on the mode of gene expression and highlights areas of trypanosome
      research that have provided paradigms of eukaryotic biology.

PMID- 7827787
TI  - Human papillomavirus vaccines: a warty problem.
AB  - Infection of the genital tract with human papillomaviruses (HPVs) is a common
      occurrence, and manifestations can include genital warts (condyloma acuminata),
      dysplasia, and invasive cancer. Approaches to diagnose and treat HPV infections
      are costly and are not fully effective. Even in populations at low risk for
      sexually transmitted diseases (STDs), HPV infection is severalfold more prevalent
      than all other STDs combined, and worldwide, uterine cervical cancer remains the
      most common cancer in women. It should be feasible to develop prophylactic
      vaccines to prevent HPV infection using the L1 and L2 capsid proteins or
      therapeutic vaccines to modulate the development or recurrence of disease based
      on the E6 and E7 oncoproteins or other viral proteins. In favor of success is (a)
      the relative simplicity of the HPV genome (only two proteins in the viral coat,
      and a small number of other genes), (b) the lack of genetic variability within
      types and stability of the genome, and (c) the encouraging results with vaccines
      against animal PVs. However, it is difficult to provide evidence of the efficacy
      of HPV vaccines because of the inability to propagate the virus in culture or in
      animal models and because of the incomplete understanding of the natural history
      of HPV infection.

PMID- 7827788
TI  - Whatever happened to AIDS?
AB  - The HIV/AIDS epidemic has caught millions of people in its path worldwide during
      the first 13 years since it surfaced; half a million Americans have been
      diagnosed with AIDS, and hundreds of thousands more are in earlier stages of HIV
      disease. Yet the sense of urgency one would expect should attend such awful
      numbers is strangely absent, prompting the bitter query "Whatever happened to
      AIDS?" This paper discusses the present status of progress with respect to the
      epidemic and explores some of the reasons that might partially explain both the
      inherent difficulties of research and the inappropriate public sense of
      quiescence. It then puts forward some suggested areas of research endeavor and/or
      public policy that could re-energize the flagging public response to this massive
      health disaster.

PMID- 7827789
TI  - RNA virus quasispecies: significance for viral disease and epidemiology.
AB  - The experimental evidence available for animal and plant RNA viruses, as well as
      other RNA genetic elements (viroids, satellites, retroelements, etc.), reinforces
      the view that many different types of genetic alterations may occur during RNA
      genome replication. This is fundamentally because of infidelity of genome
      replication and large population sizes. Homologous and heterologous
      recombination, as well as gene reassortments occur frequently during replication
      of retroviruses and most riboviruses, especially those that use enzymes with
      limited processivity. Following the generation of variant genomes, selection,
      which is dependent on environmental parameters in ways that are poorly
      understood, sorts out those genome fits enough to generate viable quasispecies.
      Chance events can also be destabilizing, as illustrated by recent results on
      fitness loss and other phenotypic changes accompanying bottleneck transmission.
      Variation, selection, and random sampling of genomes occur continuously and
      unavoidably during virus evolution. Evolution of RNA viruses is largely
      unpredictable because of the stochastic nature of mutation and recombination
      events, as well as the subtle effects of chance transmission events and
      host/environmental factors. Among environmental factors, alterations resulting
      from human intervention (deforestation, agricultural activities, global climatic
      changes, etc.) may alter dispersal patterns and provide new adaptive
      possibilities to viral quasispecies. Current understanding of RNA virus evolution
      suggests several strategies to control and diagnose viral diseases. The new
      generation of chemically defined vaccines and diagnostic reagents (monoclonal
      antibodies, peptide antigens, oligonucleotides for polymerase chain reaction
      amplification, etc.) may be adequate to prevent disease and detect some or even
      most of the circulating quasispecies of any given RNA pathogen. However, the
      dynamics of viral quasispecies mandate careful consideration of those reagents to
      be incorporated into diagnostic kits. Broadening diagnosis without jeopardizing
      specificity of detection will be challenging. There is a finite probability
      (impossible to quantify at present) that a defined vaccine may promote selection
      of escape mutants or a particular diagnostic kit may fail to detect a viral
      pathogen. Of particular concern are the potential long-term effects of weak
      selective pressures that may initially go unnoticed. Variant viruses resulting
      from evolutionary pressure imposed by vaccines or drugs may insidiously and
      gradually replace previous quasispecies. The great potential for variation and
      phenotypic diversity of some important RNA virus pathogens (human
      immunodeficiency virus, the hepatitis viruses, the newly recognized human
      hantaviruses, etc.) has become clear. Prevention and therapy should rely on
      multicomponent vaccines and antiviral agents to address the complexity of RNA
      quasispecies mutant spectra.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7827790
TI  - Hold on to your assets.

PMID- 7827791
TI  - Born to be wired.

PMID- 7827792
TI  - Role out of control.

PMID- 7827793
TI  - Arguments that wash.

PMID- 7827794
TI  - Sell-out or saviour?

PMID- 7827795
TI  - Job evaluation, know the score.

PMID- 7827796
TI  - Host or ghost purchaser?

PMID- 7827797
TI  - No shuffling on New Deal.

PMID- 7827798
TI  - Derby City General Hospital Trust's performance-related local pay scheme.

PMID- 7827799
TI  - Derby's pioneering local pay spine.

PMID- 7827800
TI  - Crying at the alter?

PMID- 7827801
TI  - Characterization of glutathione efflux from Hep G2 cells.
AB  - Previous studies have suggested that both cAMP-dependent signal transduction
      pathway and Ca2+/protein kinase C-dependent pathway are involved in GSH efflux
      from hepatocytes. In the present study, GSH efflux from Hep G2 cells, a human
      derived hepatoma cell line, was further characterized. Both epidermal growth
      factor (0.1-10 ng/ml) and insulin (1 microgram/ml) significantly increased GSH
      efflux from Hep G2 cells. A fall in the membrane potential produced by the
      replacement of Na+ with equivalent K+ did not affect GSH efflux significantly.
      Neither ouabain, a Na+/K+ ATPase inhibitor, vanadate, a Ca2+ ATPase inhibitor,
      nor BaCl2, a K+ channel blocker, significantly affected the GSH efflux.
      Methionine (1mM) decreased GSH efflux from the cells, although total GSH content
      in the cells was not affected during the incubation time of 60 min. Signal
      transductions through tyrosine kinase-coupled receptors may also be involved in
      GSH efflux from hepatocytes.

PMID- 7827802
TI  - Inhibitory effect of hepatocyte growth factor against FaO hepatocellular
      carcinoma cells may be associated with changes of intracellular signalling
      pathways mediated by protein kinase C.
AB  - Hepatocyte growth factor (HGF) stimulates growth of mature hepatocytes, whereas
      it inhibits growth of cancer cells including hepatocellular carcinoma (HCC)
      cells. However, the regulatory mechanisms for this phenomenon remains unclear. An
      important intermediary in HGF signal transduction in normal hepatocytes, c-myc,
      was not induced in FaO HCC cells after HGF stimulation, suggesting that
      intracellular signalling pathways of HGF in FaO HCC cells were different from
      those in normal hepatocytes. Protein kinase C (PKC) has been reported to be
      involved in signalling pathways of many growth factors. To study whether PKC is
      associated with this inhibitory mechanism, we studied the effects of HGF and/or
      12-O-tetradecanoyl phorbol-13-acetate (TPA) on the growth of normal hepatocytes
      and FaO HCC cells. Consequently, HGF or TPA stimulated growth of normal
      hepatocytes, while equal doses of TPA or HGF inhibited growth of FaO HCC cells,
      respectively. In addition, TPA reversed the HGF effect in both normal hepatocytes
      and FaO HCC cells. These data suggest that an inhibitory effect of HGF on FaO HCC
      cells may be associated with changes of protein kinase C-mediated intracellular
      signalling pathways.

PMID- 7827803
TI  - Characterization of catalytic properties and expression of cytochrome P
      450(14DM), lanosterol 14 alpha-demethylase, in rats.
AB  - Cytochrome P-450(14DM) catalyzing lanosterol 14 alpha-demethylation was purified
      from rat liver and was characterized by its catalytic properties and mode of
      expression. The purified protein, with an apparent molecular mass of 51 kDa,
      showed 24,25-dihydrolanosterol 14 alpha-demethylation activity (3.05 nmol/min/mg
      protein) in a reconstituted system with an apparent Km value of 40 microM. The
      reconstituted enzyme converted 32-hydroxy-24,25-dihydrolanosterol and 32-oxo
      24,25-dihydrolanosterol (the oxygenated intermediates of 24,25-dihydrolanosterol)
      to 4,4-dimethylcholesta-8,14-dien-3 beta-ol (the 32-nor compound). Immunoblot
      analysis of liver microsomes from male and female rats showed that the enzyme
      protein was expressed at an early stage of development and attained its maximum
      at 4 weeks after birth, retaining the same level thereafter. No difference was
      evident between males and females in the level of cytochrome P-450(14DM) in the
      liver up to 7 weeks after birth.

PMID- 7827804
TI  - All-or-none like responses in increment of cytoplasmic free calcium
      concentrations to histamine in single smooth muscle cells of guinea pig trachea.
AB  - Single smooth muscle cells were isolated from guinea pig trachea and cultured for
      48 hours. The cells were then loaded with a fluorescent-free calcium indicator,
      fluo-3. Concentrations of cytoplasmic-free calcium ([Ca2+]i) were determined by
      using a confocal laser scanning fluorescence imaging system. Cells exposed to
      histamine at concentrations less than 1.0 microM did not indicate any changes of
      the fluorescence intensities, but stayed at the basal level of [Ca2+]i. Cells
      exposed to histamine at a concentration in the range of 1.5 to 10 microM
      indicated marked increases in [Ca2+]i. A further increase in [Ca2+]i by
      application of higher concentrations of histamine was not observed. The threshold
      concentration of histamine to increase [Ca2+]i and peak [Ca2+]i varied from cell
      to cell. In addition, half-maximal response time was shortened with increasing
      concentrations of histamine from 1.5 to 100 microM. These results indicate that
      [Ca2+]i responses to histamine is an all-or-none type in each cell. The
      heterogeneity in the required threshold concentration of histamine to increase in
      [Ca2+]i and the concentration dependency in half-maximal response time of
      histamine-induced [Ca2+]i increase may be related to the graded responses of
      histamine-induced contractions in preparations of the tracheal tissue.

PMID- 7827805
TI  - Histological study of the parotid gland in rats treated with oxybutynin
      hydrochloride.
AB  - The purpose of this study was to determine whether oxybutynin hydrochloride
      (OBHC) induces histological changes in the parotid gland. Thirty male rats were
      divided into three groups, young (8 weeks), middle-aged (20 weeks) and old (113
      weeks). Six rats in each group were given a diet containing OBHC mixed with the
      standard food. Four rats in each group had free access to standard food as a
      control. Eight weeks after dieting, all animals were sacrificed and removed their
      parotid gland. Degeneration, dispersion of basophilic material and transformation
      of nuclear shape in the acinar cells and atrophy of duct cells were observed in 5
      young, 2 middle aged and 6 old rats. There were no appreciable histological
      changes in young and middle-aged control rats, although an aged-related effect of
      OBHC was seen in older control animals. These results indicate that chronic
      treatment with OBHC produces significant effects of aging on histological changes
      in the parotid gland of rats.

PMID- 7827806
TI  - Amelioration of diabetes and cataract by Na3VO4 plus U-83836E in streptozotocin
      treated rats.
AB  - Experimental work in our laboratory has confirmed the protective activity of
      vanadium compounds on hyperglycemia and glycosuria in streptozotocin (STZ)
      diabetes. Furthermore, diabetic cataract has also been partially prevented.
      Nevertheless, the combination of a natural antioxidant, vitamin E, with Na3 VO4
      has not further enhanced this ameliorating effect. Our experimental approach has
      been an attempt to block the prooxidant activity of both STZ and vanadate, with
      the purpose of eliciting the best possible antidiabetic protection. More
      recently, a lipid soluble synthetic antioxidant U-78517F, a 2-methylaminochroman,
      has been reported to have a significant protective effect against brain injury
      and ischemia. This compound inhibits the iron-dependent lipid peroxidation 100
      times more effectively than vitamin E. This investigation has introduced a
      combination of the vanadium compound plus the aforesaid lazaroid, as its (-)
      enantiomer, U-83836E, in order to improve the insufficient protection when
      vitamin E was used. For twelve weeks, male Wistar rats, rendered diabetic with
      STZ, were administered Na3VO4 in drinking water along with the lazaroid carried
      by the food. Four, eight and twelve weeks after the beginning of the protective
      treatment, fluid and food intake, diuresis and excreted feces, glycosuria and
      proteinuria were determined on biological samples obtained in metabolic cages;
      body weight and glycemia were also recorded. At weeks 6 and 12 of the treatment,
      the opaqueness of the eye lenses was controlled and registered. At the end of the
      experiment, circulating glycosylated hemoglobin (HbA1c), fructosamine, N-acetyl
      beta-D-glucosaminidase (NAG), and fluorescent peroxides were evaluated. Within
      the first month of treatment, protection by the combination paralleled that
      elicited by vanadate alone. At subsequent steps, U-83836E significantly improved
      the protective effect of vanadate alone on polydipsia and polyuria, but
      especially on hyperglycemia and glycosuria. The further ameliorating effect of
      the lazaroid was also observed on HbA1c and NAG, and, most important, on the
      cataract. In conclusion, these findings demonstrate that the lazaroid U-83836E
      succeeds in further protecting the most important symptoms of diabetes treated
      with vanadate, and that this antioxidant acts effectively even when it is
      administered orally in food, in a non invasive manner.

PMID- 7827807
TI  - Protective effects of the nucleic acid components on CCL4-induced liver injury in
      rats.
AB  - In our previous studies, uracil was identified as the active principle from
      Trionyx carapax. The protective effects of other nucleic acid components, and of
      xanthine are further investigated.

PMID- 7827808
TI  - Preliminary evaluation of transdermal delivery of melatonin in human subjects.
AB  - A transdermal delivery device (TDD)1 was applied to four human subjects to
      investigate whether melatonin (MT) could penetrate through human skin. The TDD
      (total surface area of 3.80 cm2) was applied to the forearm of each subject.
      Plasma MT concentrations increased above baseline in approximately 2-4 hours,
      although steady state was not achieved in the 8-hour study period. Intersubject
      variation of plasma MT among four subjects was noted. Urinary excretion of 6
      sulphatoxymelatonin (6-STMT), a major metabolite of MT in humans, increased as
      plasma MT concentrations increased. Cumulative amounts of urinary 6-STMT
      increased over a 6-hour period when the TDD was applied and were three times
      greater than in controls. The urinary excretion rate of 6-STMT was statistically
      correlated with plasma MT concentration among subjects (r2 = 0.77). These data
      suggest that the urinary excretion rate of 6-STMT can be used as an index of MT
      plasma concentrations in human subjects. Although an intersubject variability in
      both plasma MT concentration and urinary excretion rate of 6-STMT was noted, it
      was evident that MT can be delivered transdermally in human subjects.

PMID- 7827809
TI  - Induction of colon adenocarcinomas in rats fed trypsin and tamoxifen diets by
      parenteral and intragastric 1,2-dimethylhydrazine.
AB  - Male Sprague-Dawley rats, 25 days of age, were placed on a control ration and
      diets containing trypsin (2429 u/g) and tamoxifen (initial level: 4 PPM) at which
      time, 1,2-dimethylhydrazine was injected s.c. at 20 mg base/kg and continued
      once/week for 20 weeks. Most of the animals were killed 65 days after injection
      20. In view of weight losses, the tamoxifen supplement was decreased to a final
      level of 0.50 PPM without intervening control diet feeding. The total number of
      colon adenocarcinomas and the distribution in the proximal and distal portions
      did not differ significantly from the respective controls and the tumor
      frequencies in the small intestine were not remarkable. However, the general
      animal conditions, weight changes and the presence of other tumor types were more
      extreme as compared to a similar trypsin supplement reported for rats
      administered carcinogen by gavage once weekly for 15 consecutive weeks. With the
      latter series, colon adenocarcinoma frequencies were markedly decreased.

PMID- 7827810
TI  - A structure activity relationship study on 1-isopropylamino-3-(2'-substituted
      naphthoxy)-propan-2-ois analogs.
AB  - The structure activity relationship of 1-isopropylamino-3-(2'-substituted
      naphthoxy) propan-2-ois analogs, which are beta-adrenergic blocking drugs, is
      discussed. The blocking activity of these compounds is found to be dominantly
      controlled by electronic and steric factors. Significant correlations have been
      obtained between the blocking activity and negentropy, equalized eletronegativity
      and partial charge.

PMID- 7827811
TI  - High density lipoprotein inhibits platelet 12-lipoxygenase activity.
AB  - The effects of high density lipoprotein (HDL) and low density lipoprotein (LDL)
      on the formation of 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE),
      thromboxane (TX) B2 and 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT) in washed
      rabbit platelets were examined. HDL had a powerful inhibitory effect on 12-HETE
      formation, while it produced only a small increase in TXB2 and HHT formation. LDL
      did not affect the formation of 12-HETE, TXB2 and HHT. These results suggest that
      HDL is a selective inhibitor of platelet 12-lipoxygenase and may play a
      protective role in atherogenesis by preventing the generation of 12-HETE.

PMID- 7827812
TI  - Enhanced expression of catalytic subunits of protein phosphatase type 1 and high
      S-phase fraction in liposarcoma.
AB  - The expression of the three catalytic subunits of protein phosphatase (PP) type 1
      and 2A, PP1 alpha, PP1 gamma 1, and PP2AC, was examined in 8 cases of lipoma as a
      benign tumor and 4 cases of liposarcoma as a malignant tumor using
      immunohistochemical analysis. Both types of of tumor cells stained positively
      with antisera against PP1 catalytic subunit isoforms PP1 alpha and PP1 gamma 1
      were significantly higher in liposarcoma than in lipoma. Furthermore, liposarcoma
      showed a markedly high S-phase fraction in the cell cycle of tumor cells, as
      compared with lipoma. These results suggest that PP1 is involved in the
      accelerated growth of malignant cells in liposarcoma.

PMID- 7827813
TI  - Chronic prostatitis.

PMID- 7827814
TI  - Ultrasound evaluation of the paediatric prostate.
AB  - OBJECTIVE: To document the shape, echogenicity and volume range of the normal
      paediatric prostate on transabdominal ultrasound, and to determine the
      feasibility of imaging the seminal vesicles and prostatic urethra with
      transabdominal ultrasound. PATIENTS AND METHODS: Transabdominal ultrasound of the
      prostate was performed in 36 boys, aged 7 months-13.5 years (mean 7.7 years),
      with normal prostates. RESULTS: Generally the prostate was hypoechoic,
      ellipsoidal in shape with a volume range of 0.4-5.2 ml (mean 1.2). The seminal
      vesicles were demonstrated in 56% of boys but only occasionally could the urethra
      be visualized. No colour flow was demonstrated within the prostate. CONCLUSION:
      The paediatric prostate can be easily visualized by transabdominal ultrasound.
      This technique may be of value in the investigation of incontinence, posterior
      urethral valves and seminal vesicle pathology, and in the monitoring of prostatic
      volume in hypogonadal boys.

PMID- 7827815
TI  - Standardized in vitro mapping with multiple core biopsies of total prostatectomy
      specimens: localization and prediction of tumour volume and grade.
AB  - OBJECTIVE: To analyse the ability of systematic core biopsy mapping to provide
      prognostic information in patients with prostatic cancer. MATERIALS AND METHODS:
      The prostates of 60 men with prostatic cancer, stages T0d-T2, who had undergone
      total retropubic prostatectomy were studied. The average age of the patients was
      63 years (range 49-72). Ten core biopsies (1.2 x 35 mm) were taken from the fresh
      specimens according to a standardized procedure. The total prostatectomy
      specimens were serially step-sectioned at 5 mm intervals and were assessed
      regarding tumour volume, grade and pT-stage. The World Health Organization (WHO)
      grade obtained in the mapping biopsies was compared with that in the operative
      specimens. Undergrading (WHO) decreased substantially by mapping biopsies, but
      was still present with the Gleason system. RESULTS: The volume of extracapsular
      tumours with extensively positive margins was significantly larger than that of
      intracapsular tumours (P < 0.01). In addition, the fraction of cancer obtained in
      the biopsies from tumours with grossly positive margins was significantly smaller
      than that observed in biopsies from pT2 tumours (P < 0.01). The cancer volume
      calculated from the result of the mapping correlated positively with the tumour
      volume determined by planimetry (R = 0.83). A weaker correlation was found when
      only the six dorsal mapping biopsies were taken into consideration (R = 0.68),
      but the correlation increased to R = 0.75 when the six most significant biopsies
      were selected with the help of a correlation matrix. Biopsies from the ventral
      part of the prostate were also important, to obtain an accurate assessment of the
      tumour fraction within the whole gland. CONCLUSION: Mapping of the prostate gland
      with multiple (six or more) core biopsies is necessary for preoperative
      assessment of tumour volume, grade and pT stage; these are all of importance when
      assigning patients with clinically localized prostatic cancer to prognostic
      classes.

PMID- 7827816
TI  - Conservative management with symptomatic treatment and delayed hormonal
      manipulation is justified in men with locally advanced carcinoma of the prostate.
AB  - OBJECTIVE: To examine the clinical course following surveillance and symptomatic
      treatment, and compare the outcomes of immediate and delayed hormonal treatment
      in men with locally advanced prostatic cancer. PATIENTS AND METHODS: Of a
      consecutive series of 199 men (mean age 74 years) with T2-T4 Nx M0 prostatic
      cancer, 110 (55%) were followed until death and the rest had a mean follow-up of
      4.2 years. Fifty-one men received immediate orchidectomy, 88 had this treatment
      delayed until metastatic progression, and 60 had the treatment in the intervening
      period. The actuarial survival was compared with the expected survival for an age
      matched healthy population in Scotland. The adjusted effect of the timing for
      hormonal manipulation was assessed by including it with age, Gleason score and
      clinical stage in a multiple Cox regression. RESULTS: The actuarial survival for
      the whole group was 17% less at 5 years and 15% less at 10 years when compared
      with the expected survival for an age-matched population in Scotland. This was
      despite the fact that their nodal status was unknown and also those with occult
      metastasis (elevated serum prostatic acid phosphatase, M1a) at presentation were
      not excluded. In terms of metastatic progression, overall survival and cause
      specific survival, there was no significant difference between immediate and
      delayed hormonal treatment. CONCLUSION: A conservative approach with surveillance
      and symptomatic treatment for locally advanced prostatic cancer is justified by
      the present evidence on disease progression and survival, which do not differ
      from alternative methods of treatment as reported in contemporary literature.
      This study has the limitations relative to the ideal of a prospective randomized
      trial on immediate versus delayed hormonal treatment, but the lack of significant
      differences in outcome even after adjustment for other established prognostic
      factors does suggest that there may be little to be gained from an immediate
      orchidectomy.

PMID- 7827817
TI  - The management of bilateral ureteric obstruction and renal failure in advanced
      prostate cancer.
AB  - OBJECTIVES: To investigate the effect of upper tract decompression on the
      prognosis of uraemia secondary to bilateral ureteric obstruction in prostate
      cancer, with particular reference to the hormone dependency of the tumour.
      PATIENTS AND METHODS: Prospectively collected data, over the period 1978-1993,
      were selected from the departmental database and from hospital case code data.
      Inclusion criteria were: blood urea > or = 15 mM, radiological evidence of
      bilateral ureteric obstruction, a histological diagnosis of prostate cancer, and
      the exclusion of out-flow tract obstruction. Of the 820 patients recorded in the
      departmental database, 27 (3.3%) fulfilled the criteria. Thirty-six patients were
      identified in total. Statistical analysis was by the Mann-Whitney non-parametric
      test. RESULTS: Of the 36 patients with bilateral ureteric obstruction and renal
      failure, in those in whom androgen depletion had been undertaken after ureteric
      obstruction (i.e. androgen depletion was a treatment option), the mean survival
      was 646 days (n = 12, SD = 786). Among these patients upper tract decompression
      improved survival and reduced the amount of time patients spent in hospital. In
      those in whom androgen depletion had been carried out before obstruction (i.e.
      the tumour had escaped from hormonal control), survival was significantly worse
      (80 days, n = 24, SD = 86.8, P < 0.01). In this group the use of decompression
      improved survival little. Percutaneous nephrostomy was the commonest means of
      decompression (nephrostomy, 9; stent, 5; ureteroneocystostomy, 2). DISCUSSION: In
      patients for whom hormonal therapy remains an option, upper tract decompression
      offers a worthwhile improvement in terms of increased survival and reduced in
      patient time. However, if ureteric obstruction is diagnosed after hormone
      manipulation has been used, upper tract decompression has little effect on
      survival and should only be used in exceptional circumstances.

PMID- 7827818
TI  - Quality of life in patients treated for penile cancer. A follow-up study.
AB  - OBJECTIVES: To study the long-term psychosocial well-being of patients following
      successful physical treatment for cancer of the penis. PATIENTS AND METHODS:
      Thirty patients (median age at follow-up 57 years, range 28-75) were followed up
      for a median of 80 months after treatment for penile cancer (local excision/laser
      beam treatment, 5; radiotherapy, 12; partial penectomy, 9; total penectomy, 4).
      They underwent a semi-structured interview and completed the Impact of Events
      Scale, General Health Questionnaire and the EORTC QLQ C-30 questionnaire. Global
      scales for measuring sexual function, subjective well-being and social activity
      were constructed and found reliable and valid. RESULTS: There was a strong
      correlation between the well-being scale and the EORTC scales for overall quality
      of life and psychological distress. Patients treated with partial or total
      penectomy had a worse outcome with regard to sexual function than patients
      treated conservatively, but there was no difference in the other domains of
      quality of life, indicating that even the more radically treated patients usually
      adapted adequately. Half of the individuals had mental symptoms at follow-up, and
      these patients were less satisfied and showed less social activity. Seven men
      reported that, if asked again, they would choose treatment with lower long-term
      survival to increase the chance of remaining sexually potent, but the majority
      gave priority to higher long-term survival. CONCLUSION: Before treatment of
      penile cancer, physicians should thoroughly discuss the expected outcome and
      consequences of the different treatment options with the patient. Psychosocial
      treatment might be helpful for patients with mental symptoms.

PMID- 7827819
TI  - Walk-in, walk-out day case genito-scrotal surgery with sedation reversal. A
      survey of patient attitudes and morbidity.
AB  - OBJECTIVES: To survey patient attitudes and assess the extent of patient
      morbidity in the first 24 h following walk-in, walk-out day case genito-scrotal
      surgery with sedation reversal. PATIENTS AND METHODS: One hundred patients who
      were undergoing genito-scrotal surgery were eligible for inclusion in the study.
      All patients walked into theatre, positioned themselves on the operating table
      and were sedated with intravenous (i.v.) midazolam (Hypnovel, Roche Products Ltd,
      Welwyn, UK) following which the appropriate local anaesthetic block was
      performed. One minute before the end of surgery sedation was reversed with an
      i.v. injection of 0.5 mg flumazenil (Anexate, Roche Products Ltd). When conscious
      and alert (approx. 2 min), patients were allowed to get themselves up off the
      operating table and walk from theatre. All patients were given a questionnaire to
      complete and were reviewed 2 weeks after surgery. RESULTS: Eighty-six of 100
      patients returned questionnaires. Fifty-five patients were asymptomatic and no
      patient experienced nausea or vomiting in the first 24 h post-operatively. Other
      symptoms such as headache (2%), drowsiness (20%) and dizziness (11%) were
      uncommon and significantly less frequent than seen with general anaesthetic
      procedures. Seventeen patients described minor wound complications and one
      patient with a scrotal haematoma was readmitted for overnight observation. Nearly
      all patients (98%) expressed their satisfaction with the technique. CONCLUSION:
      Walk-in, walk-out day case surgery as described is a well-tolerated technique
      with a low morbidity and towards which patients have a positive attitude.

PMID- 7827820
TI  - Female cysto-urethrectomy.

PMID- 7827821
TI  - A new technique for one-stage correction of penoscrotal hypospadias in adults.

PMID- 7827822
TI  - Screening for malignancies in patients with recurrent venous thrombosis.

PMID- 7827823
TI  - Haemorrhagic infarction of a prolapsed orthotopic ureterocele causing upper
      urinary tract obstruction.

PMID- 7827824
TI  - Acute renal failure precipitated by luteinizing-hormone releasing hormone
      analogue for the treatment of endometriosis.

PMID- 7827825
TI  - Giant vaginolith around an unusual foreign body--an uncommon cause of urinary
      incontinence in a girl.

PMID- 7827826
TI  - Retroperitoneal endoscopic excision of renal cysts.

PMID- 7827827
TI  - Painless scrotal bruising following extracorporeal shock wave lithotripsy for
      renal calculus.

PMID- 7827828
TI  - Accessory scrotum.

PMID- 7827829
TI  - Treatment of priapism with ethyl chloride spray after failed intracavernous
      injection with adrenaline.

PMID- 7827830
TI  - Renal cell carcinoma of the kidney and hypertrichosis lanuginosa acquisita.

PMID- 7827831
TI  - The use of a buccal mucosa patch graft in the management of a large
      urethrocutaneous fistula.

PMID- 7827832
TI  - Same day diagnostic service for new cases of haematuria.

PMID- 7827833
TI  - Morphological change in the urothelium after electrohydraulic versus pulsed dye
      laser lithotripsy.
AB  - OBJECTIVE: To observe morphological changes in the urothelium after exposure to
      laser beam and electrohydraulic spark. MATERIALS AND METHODS: The pulse dye laser
      lithotripter (MDL-2, Candela Corporation, Boston, USA) and the electrohydraulic
      lithotripter (AEH-2, Circon ACMI Corporation Stamford, USA) were used directly on
      the bladder mucosa in six pigs. Immediately after treatment, the bladder mucosa
      was prepared for light microscopic and scanning electron microscopic examination.
      RESULTS: Both electrohydraulic spark and laser beam caused mucosal denudation,
      submucosal swelling and haemorrhage. There was a positive correlation between the
      degree of urothelial damage and the power and pulse numbers applied. CONCLUSION:
      Direct contact of the urothelium in patients treated with laser beam or
      electrohydraulic spark should be avoided.

PMID- 7827834
TI  - A comparison of intramuscular ketorolac and pethidine in the alleviation of renal
      colic.
AB  - OBJECTIVE: To compare the analgesic efficacy of a single 30 mg intramuscular dose
      of ketorolac with that of intramuscular pethidine 100 mg, in a double-blind,
      parallel-group investigation of patients presenting with pain suggestive of renal
      colic. PATIENTS AND METHODS: Seventy-six patients (17 women, 15 men; mean age
      45.2 years, range 20-80) were allocated by means of a pre-determined
      randomization schedule to receive ketorolac and 78 patients (20 women, 58 men;
      mean age 42.1, years range 18-70) to receive pethidine. Data from eight patients
      in the ketorolac group and six in the pethidine group were excluded from the
      efficacy analyses because of protocol violations. The severity of each patient's
      pain was assessed on a four-point verbal rating scale (VRS) and a 10 cm visual
      analogue scale at pre-dose and at 15 min intervals for the first hour post
      dosing. The time to first administration of rescue analgesic, up to 24 h
      following dosing with the study medication, was recorded. Adverse events were
      elicited by general questioning. RESULTS: Eighty-eight per cent of patients in
      each treatment group had improved according to the VRS of pain severity 1 h after
      dosing; the summed pain intensity differences up to 1 h were statistically
      significantly different in favour of ketorolac (P < 0.05). Fifty-six per cent of
      patients who were receiving ketorolac required rescue analgesia during the study
      period compared with 74% receiving pethidine. The incidences of adverse events
      were lower in the ketorolac group (28%) than the pethidine group (51%).
      CONCLUSION: Ketorolac can be considered a viable alternative to pethidine for the
      treatment of renal colic.

PMID- 7827835
TI  - Treatment of ureteric stones. Comparison of laser and pneumatic lithotripsy.
AB  - OBJECTIVES: To study the treatment of ureteric stones by laser lithotripsy (LL)
      and pneumatic lithotripsy (PL), and to evaluate the results of the two treatment
      modalities to assess effectiveness, complications and cost benefits. PATIENTS AND
      METHODS: Between January 1993 and February 1994 200 ureteric stones in 194
      patients were fragmented intracorporeally, 48 by LL and 152 by PL. The ages of
      the patients ranged from 31 to 40 years with a male to female ratio of 2:1. All
      procedures were performed under general/regional anaesthetic in a day-care set
      up. Patients were followed at weekly intervals. Re-treatment was carried out at 4
      weeks where necessary. RESULTS: The majority of the stones treated (84%) were in
      the lower third of the ureter, 69% measured 7-12 mm in diameter, and 61% were
      composed of calcium oxalate. Ninety-three per cent of the stones were fragmented
      in one treatment session. The overall stone-free status at 4 weeks was 95% for PL
      and 84% for LL. The non-fragmentation rate was 10% for LL and 1% for PL. Post
      treatment complications were encountered in 8% of the patients treated by LL and
      7% by PL. CONCLUSIONS: Our experience shows that PL and LL both provide a safe
      and effective means of performing intracorporeal lithotripsy for smaller ureteric
      stones. However, PL is more effective in fragmenting larger and harder stones.
      Moreover, PL is more user-friendly and highly cost-effective compared with LL.

PMID- 7827836
TI  - Intracorporeal lithotripsy with the Swiss lithoclast.
AB  - OBJECTIVE: To evaluate the use of the Swiss lithoclast in the management of
      urinary calculi. PATIENTS AND METHODS: Between January and November 1993, 60
      patients with a total of 61 urinary calculi were treated with the Swiss
      lithoclast. Forty patients had a ureteric calculus, two had a ureterocele with a
      calculus, one a steinstrasse, 16 a vesical stone and two a urethral calculus.
      Eighty per cent of patients were treated on a day-care basis. RESULTS:
      Fragmentation of the urinary calculi was successful in 59 of the 60 patients.
      Both patients with a urethral calculus and 15 of 16 with a vesical calculus were
      stone-free after the procedure. All those with a ureteric calculus were stone
      free at 6 weeks. There were no intra-operative or long-term complications
      directly related to the use of the Swiss lithoclast. CONCLUSION: The results of
      this study show that the Swiss lithoclast is a simple, safe, reliable and
      economical method of endoscopic lithotripsy for the treatment of urinary tract
      calculi. Although the lithoclast's use is limited to rigid or semi-rigid
      endoscopes there is now a suction facility for the immediate removal of small
      stone fragments.

PMID- 7827837
TI  - Ultrasonography of ureteric abnormalities induced by Schistosoma haematobium
      infection before and after praziquantel treatment.
AB  - OBJECTIVE: To describe the ultrasonographic appearance of ureteric lesions due to
      Schistosoma haematobium infection and to report prevalence rates of such lesions
      in endemic communities in Mali before and after praziquantel treatment. SUBJECTS
      AND METHODS: The total population (n = 961) of three S. haematobium-endemic
      villages in Mali was examined ultrasonographically to detect urinary tract
      morbidity. Urine was tested for S. haematobium ova and for haematuria. An
      identical follow-up study was performed 1 year after mass treatment with
      praziquantel. RESULTS: Prevalence rates of S. haematobium infection in the three
      villages were 53%, 72% and 73%. Ultrasonography revealed dilatation of the
      ureters in 143 subjects (15%). In 20 of these, mainly children and adolescents,
      thickening and irregularities of the ureteric wall with distal ureter obstruction
      were directly visualized on ultrasonography. Within the bladder of two others, an
      intraluminal structure of ureterocele-like appearance was seen. None of these
      alterations has been previously described as an ultrasonographic feature of
      schistosomal uropathy. Active S. haematobium infection and microhaematuria were
      found in 21 and 20 of these 22 subjects respectively. Significant renal
      obstruction was present in 10 of them. One year after treatment, an entirely
      normal urinary tract was found in 85% of 104 re-examined individuals who had had
      ureter dilatation. Ureteric wall thickening or ureterocele-like lesions had
      disappeared in 95% of subjects. CONCLUSIONS: The role of ultrasound in the
      evaluation of schistosomal uropathy is confirmed. Ureteric wall abnormalities
      causing strictures and ureterocele-like lesions of the ostium must be regarded as
      further ultrasonographic features of this condition. The study documents the
      excellent reversibility of ureteric abnormalities after antischistosomal
      treatment in children and adolescents, thus emphasizing the need for early and
      efficient medical treatment of the infection.

PMID- 7827838
TI  - Correction of vesico-ureteric reflux by subureteric fibrin injection in dogs.
AB  - OBJECTIVE: To study the histological and radiological potential of the
      biomaterial fibrin in the treatment of vesico-ureteric reflux by a subureteric
      injection. MATERIALS AND METHODS: For histological studies the bladders of 22 non
      refluxing adult female dogs were exposed and in 20 of these two-component fibrin
      glue was injected into the right subureteric intramuscular portion of the bladder
      and teflon was injected into the lamina propria of the left ureter; two of them
      acted as controls. Two dogs were killed on alternate days over the course of 21
      post-operative days and the bladders and distal portions of the ureters were
      examined histologically. For radiological studies micturating cystograms were
      obtained from 15 female puppies. In only eight puppies was vesico-ureteric reflux
      naturally present. In six of these two-component fibrin was injected into the
      right and teflon into the left subureteric areas, and in two puppies fibrin was
      injected into the subureteric areas, while the left sides acted as controls.
      Micturating cystograms and intravenous urograms were obtained from all puppies 3
      weeks post-operatively. RESULTS: Histopathological studies showed persistence of
      increased amounts of endogenous collagen at the fibrin-injected sites; at the
      Teflon-injected sites a mass surrounded by dense granulation tissue was seen.
      Radiological studies revealed complete disappearance of reflux in the study group
      of six fibrin and Teflon-injected puppies; in two control puppies fibrin was
      injected into the right subureteric area only; the left sides were left untouched
      to show that maturation did not play a role in abolishing the spontaneously
      occurring reflux. Follow-up intravenous urography showed no evidence of vesico
      ureteric obstruction in the treated ureters. CONCLUSION: Fibrin has the
      properties of a substance inducing a controlled increase in the number of
      endogenous collagen fibres.

PMID- 7827839
TI  - A modified extravesical technique for megaureter repair.
AB  - OBJECTIVE: To report on the use of extravesical detrusorraphy for megaureter
      repair. PATIENTS AND METHODS: Twenty-three children underwent an extravesical
      megaureter repair over a 25 month period. There were 17 boys and 6 girls with an
      average age of 4.4 years. Three children had bilateral megaureters for a total of
      26 repairs. Ureters were defined as megaureters if the ureteric diameter exceeded
      1.0 cm on pre-operative imaging. There were 14 obstructing and 12 refluxing
      ureters. Three of the refluxing ureters were tapered while five of the
      obstructing megaureters were tapered. RESULTS: Twenty-one of the 23 patients were
      successfully repaired using this method. Complications were minimal. CONCLUSION:
      The extravesical approach can be used to correct reflux or obstruction in dilated
      ureters with efficacy equivalent to transvesical repairs.

PMID- 7827840
TI  - Recurrent symptoms of urinary tract infection in eight patients with refluxing
      ureteric stumps.
AB  - OBJECTIVES: To evaluate and discuss the recurrent symptoms presented by eight
      patients with refluxing ureteric stumps. PATIENTS AND METHODS: Eight patients
      (three boys, five girls; mean age: 8 years, range 11 months-14 years) with
      refluxing ureteric stumps presented with recurrent urinary tract infections. Six
      developed symptoms mimicking pyelonephritis, even though the kidney had been
      partially [5] or totally [3] removed. The stump was removed in all patients.
      RESULTS: The stumps that were excised measured between 5 and 10 cm in length and
      were always dilated and inflamed. The results of histological examination and
      follow-up are reported. CONCLUSIONS: A dual approach is recommended when complete
      excision of the kidney and ureter is required. Symptoms of pyelonephritis are not
      pathognomonic of parenchymal infection but reflect infection above the vesico
      ureteric junction. The distinction between supra-junctional and infra-junctional
      urinary tract infections seems more appropriate and is discussed.

PMID- 7827841
TI  - Significance of the evaluation of asymptomatic microscopic haematuria in young
      men.
AB  - OBJECTIVE: To evaluate the extent of diagnostic evaluation that is necessary in
      young men with asymptomatic microscopic haematuria. PATIENTS AND METHODS: A group
      of 157 men (mean age 24.8 years [range 18-53]) who presented with asymptomatic
      haematuria were investigated with repeated urine analysis. Addis count, urinary
      cultures, blood tests, ultrasonography, pyelography, cystourethroscopy and
      finally renal biopsy. RESULTS: The results showed pathological findings in 31.2%
      of patients. Of the 157 individuals, 33.1% did not complete the study. In 14.6%
      urological disease was found, including two patients with urothelial cancer.
      Renal biopsy detected glomerulopathy in 16.5% of all patients. IgA nephritis
      being the most common diagnosis (42% of all biopsies). CONCLUSION: Even in young
      patients, microscopic haematuria should be investigated and followed thoroughly.
      Renal biopsy seems to be optional: once a diagnosis is established repeated and
      unnecessary examinations can be avoided.

PMID- 7827842
TI  - Repeat testing for haematuria and underlying urological pathology.
AB  - OBJECTIVE: To assess the incidence of urological pathology in a group of patients
      referred for the investigation of haematuria and whose symptoms had resolved at
      the time of investigation. PATIENTS AND METHODS: The results from examination of
      395 patients attending for investigation of haematuria were analysed. The group
      comprised 198 men and 197 women with a mean age of 51 years (range 19-73).
      RESULTS: In 220 patients (56%) no evidence of haematuria was detected despite its
      diagnosis in all patients at the time of referral. One-hundred and thirteen
      patients (51%) without detectable haematuria had urological pathology and 16 of
      these (14%) had an underlying malignancy in the urinary tract. CONCLUSION: Repeat
      urine analysis to determine whether haematuria persists has been considered as a
      way to define a high risk group which requires urgent investigation. Our results
      clearly indicate that the finding of haematuria, even in one urine specimen,
      warrants full urological assessment.

PMID- 7827843
TI  - Desmopressin in the treatment of nocturia and enuresis in patients with multiple
      sclerosis.
AB  - OBJECTIVES: To assess whether the synthetic vasopressin analogue desmopressin [1
      desamino 8-D-arginine vasopressin] is efficacious and safe in the management of
      nocturia +/- enuresis in patients with multiple sclerosis. PATIENTS AND METHODS:
      Twenty-two women and 11 men, under 65 years of age, with clinically definite
      multiple sclerosis and nocturnal frequency +/- enuresis were entered into the
      study. A two week placebo run-in, to establish normal voiding patterns, followed
      by a double-blind, placebo-controlled, cross-over study of 20 micrograms
      intranasal desmopressin at night-time was carried out. RESULTS: Desmopressin
      caused a significant decrease in nocturnal urinary frequency, nocturnal urinary
      volume and the percentage of total daily urine passed at night. There was no
      significant fall in plasma sodium with desmopressin although there were two cases
      of asymptomatic hyponatraemia. CONCLUSION: Desmopressin is an efficacious and
      safe treatment for nocturia +/- enuresis in patients with multiple sclerosis.

PMID- 7827844
TI  - Excitatory neurotransmission in the mammalian bladder and the effects of suramin.
AB  - OBJECTIVE: To compare the electrical and mechanical activity, and assess the
      effect of suramin on strips of detrusor from various species. MATERIALS AND
      METHODS: Bladder muscle strips from guinea-pigs, rabbits, monkeys and sheep and
      detrusor strips from humans (obtained at operation) were studied. The mechanical
      responses to nerve stimulation were recorded with a force transducer and
      electrical activity was recorded with the double sucrose gap. RESULTS: In all
      species acetylcholine was released from the nerves and a prolonged contraction
      was produced. A second transmitter, possibly adenosine triphosphate, produced a
      rapid transient contraction, the amplitude of which varied with the species. In
      the rabbit and guinea-pig the phasic contraction and accompanying depolarization
      were large, whereas in primates they were small and in sheep were intermediate.
      At high concentrations, suramin reduced the contraction and accompanying
      depolarization in rabbit and guinea-pig muscle but not in sheep. Suramin enhanced
      the late cholinergic responses and increased spontaneous mechanical activity in
      all species. These latter effects were not seen after desensitization of the
      receptors with the ATP analogue alpha, beta- methylene ATP. CONCLUSION: Although
      suramin reduces the excitatory effect of nerve activity in some species, it would
      produce little beneficial effect in the human hyperexcitable bladder as any
      inhibitory effect might be offset by the increase in spontaneous activity.

PMID- 7827845
TI  - An assessment of the contribution of visco-elastic factors in the aetiology of
      poor compliance in the human neuropathic bladder.
AB  - OBJECTIVE: To compare the mechanical properties of fullthickness bladder strips
      from poorly compliant neuropathic bladders with controls and to determine the
      overall contribution that mechanical factors might have in the aetiology of the
      poor compliance of medium-fill cystometry. PATIENTS AND METHODS: The visco
      elastic properties of full-thickness bladder strips from 11 neuropathic patients
      (with poorly compliant bladders during medium-fill cystometry) were compared with
      strips from 11 control bladders. A strip (measuring 2 cm long and 0.5 cm wide)
      was mounted in an organ bath and stretched by 1 cm at a slow and at a fast rate.
      The stretches were repeated in modified Krebs solution containing zero calcium
      and 12 mM magnesium. The final experiment involved stretching the strip by 1 cm
      in < 1 s (instantaneous stretch). RESULTS: Only modest differences in the peak
      tensions of both tissues were uncovered by the slow and fast stretches (fast
      stretch: 14.6 +/- 5.5 in neuropaths vs 10.1 +/- 4.1 g in controls, P = NS; slow
      stretch: 9.6 +/- 3.5 in neuropaths vs 6.7 +/- 2.5 g in controls, P < 0.05).
      Stretches carried out in modified Krebs solution resulted in lower tensions.
      Fast, intermediate and slow components of viscous decay (derived from the rate of
      tension decay following the instantaneous stretch) were not significantly
      different in neuropaths compared to controls (P = NS). CONCLUSION: The
      differences in the mechanical properties between neuropathic and control bladder
      strips were small and could not alone have accounted for the large differences in
      bladder compliance that was observed between neuropathic and normal patients
      during medium-fill cystometry. This implied that neurogenic rather than
      mechanical factors were more important in the aetiology of the observed poor
      compliance in these patients.

PMID- 7827846
TI  - Bladder neck anatomy and mobility: effect of vaginal ultrasound probe.
AB  - OBJECTIVE: To evaluate the effect of a vaginal ultrasound probe on bladder neck
      anatomy and mobility. PATIENTS AND METHODS: Twenty women, 15 with urinary
      incontinence and five with other urological complaints, were studied. Colpocysto
      urethrography (CCU) during rest. Valsalva and withholding manoeuvres were
      compared with and without simultaneous vaginal endosonography. The CCU diagnoses
      and measurements of bladder neck position and mobility in relation to the
      symphysis pubis were compared with and without the probe inserted. A small, 7 MHz
      vaginal probe (Bruel and Kjaer, type 1846) was used with the scanning field 45
      degrees to the long axis of the probe. RESULTS: The CCU diagnoses as well as the
      measurements of bladder neck position and mobility relative to the symphysis
      pubis were unaffected by the insertion of this probe. CONCLUSION: Vaginal
      ultrasonography is a minimally invasive technique; it is convenient for routine,
      firstline evaluation of bladder neck anatomy and mobility in incontinent women.

PMID- 7827847
TI  - Urothelial cancer and cigarette smoking: findings from a regional case-controlled
      study.
AB  - OBJECTIVE: To quantify the risks of urothelial cancer associated with smoking
      cigarettes. SUBJECTS AND METHODS: Histories were taken from 989 patients
      diagnosed with urothelial cancer, 2059 electoral register controls and 1599
      General Practitioner controls. Histories of patients and controls were compared
      by means of logistic regression. RESULTS: Statistically significant trends were
      observed for the risk of urothelial cancer to increase with estimated lifetime
      consumption of cigarettes. Among ex-smokers, risks reduced with time since
      quitting, and ex-smokers who quit 20 or more years ago experienced risks similar
      to lifelong non-smokers. Type of cigarette was not an important predictor of
      risk. The two control series provided estimates of 45% and 33% respectively for
      the percentage of cancers in the series attributable to cigarette smoking.
      CONCLUSION: Cigarette smoking is the single most important cause of urothelial
      cancer, but stopping smoking leads quickly to reductions in risk.

PMID- 7827848
TI  - c-jun oncogene expression in transitional cell carcinoma of the urinary bladder.
AB  - OBJECTIVE: To investigate c-jun oncoprotein expression in transitional cell
      carcinomas (TCCs) of the urinary bladder and to determine its relationship to
      tumour grade and stage, and to the expression of epidermal growth factor receptor
      (EGFR), c-erbB-2 and p53 oncoproteins. MATERIALS AND METHODS: The expression of c
      jun was studied using immunohistochemistry in a series of 48 TCCs of known EGFR,
      c-erbB-2 and p53 status. RESULTS: Forty-four of 48 (92%) tumours showed c-jun
      specific nuclear immunoreactivity of variable intensity. The intensity of c-jun
      immunostaining was significantly related to tumour stage (P = 0.009) and EGFR
      status (P = 0.01). There was no correlation between c-jun oncoprotein expression
      and c-erbB-2 or p53 immunoreactivity. c-jun expression was not related to
      clinical outcome in terms of patient survival or rate of tumour recurrence.
      CONCLUSION: The c-jun oncoprotein is expressed in the majority of TCCs of the
      urinary bladder. There is a positive association between intense c-jun
      immunoreactivity and muscle invasive growth, and EGFR positivity in TCCs.

PMID- 7827849
TI  - Positron emission tomography with L-methyl-11C-methionine in the monitoring of
      therapy response in muscle-invasive transitional cell carcinoma of the urinary
      bladder.
AB  - OBJECTIVE: To investigate whether positron emission tomography (PET) with L
      methyl-11C-methionine as a tracer could be used for diagnostic purposes and for
      evaluation of therapy in patients with varying stages of urinary bladder cancer
      treated with chemotherapy. PATIENTS AND METHODS: PET was employed in 44 separate
      examinations involving 29 patients (24 men and five women with a median age of 68
      years [mean 66, range 47-78]) with localized or metastatic transitional cell
      carcinoma of the urinary bladder. In four patients PET examinations were
      performed prior to the commencement of chemotherapy, and after one course and
      after three courses. RESULTS: The diagnostic accuracy of PET was poor. The
      technique did not monitor the therapeutic effect of neoadjuvant chemotherapy,
      producing results that correlated with therapy outcome. PET identified those
      patients who responded less successfully to therapy. CONCLUSION: PET with L
      methyl-11C-methionine demonstrates alterations in tumour metabolism long before
      visible changes appear on computed tomography or magnetic resonance imaging.
      Further work is required to develop more specific tracers.

PMID- 7827850
TI  - Partial bladder reconstruction with pedicled rectus and gracilis muscle flaps: an
      experimental study in dogs.
AB  - OBJECTIVE: To investigate the functional, anatomical and histopathological
      results of partial bladder reconstruction with skeletal muscle flaps. MATERIALS
      AND METHODS: Partial bladder reconstruction with gracilis or rectus muscle flaps
      was performed in 10 mongrel dogs. Bladder compliance and uninhibited contractions
      were investigated in five female dogs. Pre-operative and post-operative
      cystograms were performed in four female dogs. The dogs were killed 8-12 weeks
      after the operation. Bladders and muscle flaps were grossly examined and removed
      for histopathological examination. RESULTS: There was no extravasation on post
      operative cystography. Bladder compliance was normal and uninhibited contractions
      were not present. Severe contracture and atrophy of the muscle flaps were
      observed in all dogs at necropsy. Bladder volumes were not changed significantly
      (P > 0.05). Histopathological examination revealed severe mesenchymal metaplasia
      in all of the flaps. CONCLUSION: Partial reconstruction of the bladder with
      skeletal muscle flaps did not result in extravasation and bladder function was
      not altered. However, bladder volume could not be increased because of
      contracture and atrophy of the flaps.

PMID- 7827851
TI  - Extent of blood transfusion and cancer-related mortality after cystectomy and
      urinary diversion for bladder cancer.
AB  - OBJECTIVE: To assess the possible adverse effect of peri-operative blood
      transfusion on cancer-related survival after radical cystectomy for bladder
      cancer. PATIENTS AND METHODS: The hospital records of 130 patients treated with
      cystectomy and urinary diversion for bladder cancer between 1967 and 1986 were
      retrospectively reviewed. RESULTS: Standard proportional hazards estimation
      revealed tumour stage and radiation response after pre-operative irradiation to
      be significantly associated with cancer-related mortality, whereas age, tumour
      grade or the extent of peri-operative blood transfusion were not. In models which
      allowed time varying effects a significantly changed effect of blood transfusion
      (> or = 7 versus < or = 6 units) was observed, from an initially insignificantly
      increased relative hazard (RH) (RH = 1.44 at 6 months) to an insignificantly
      decreased effect after longer follow-up (RH = 0.53 after 2 years). CONCLUSION:
      Although no overall association between blood transfusion and cancer-related
      mortality was found, a tendency towards an increased risk early in the follow-up
      period was observed if more than 6 units were transfused. However, these results
      need confirmation in further studies before a restrictive attitude towards peri
      operative blood transfusion is recommended.

PMID- 7827852
TI  - Mercapto-acetyltriglycine (MAG 3) renography and indirect radionuclide
      cystography in posterior urethral valves.
AB  - OBJECTIVE: To assess dynamic isotope renography with 99mTc-labelled mercapto
      acetyltriglycine (MAG 3) in conjunction with indirect radionucleide cystography
      (IRC) in the follow-up of boys with posterior urethral valves. PATIENTS AND
      METHODS: Fifty-one boys (95 renal units; mean age = 89 months, range 65-118) with
      previously treated posterior urethral vales underwent MAG 3 renography followed
      by IRC. Glomerular filtration rate (GFR) was estimated from the plasma clearance
      of 51Cr-ethylenediamine tetra-acetic acid following single intravenous injection.
      Renographic parameters noted were renal function based on the quality of renal
      visualization and background activity as well as renal drainage and the
      appearance of isotope in ureter and bladder. Following the dynamic 20 min MAG 3
      renogram the child was allowed to leave the department and to return when he
      wished to void. IRC was then performed. Diuretics were not administered. RESULTS:
      Initial drainage from 30 kidneys was normal, in 36 drainage was delayed and in 25
      drainage did not occur during the renogram phase. In four kidneys function was so
      poor as to preclude assessment. After the IRC, drainage was noted in 17 of 25
      units which had not drained during the renogram, six units did not drain and in
      two drainage was equivocal due to the presence of vesico-ureteric reflux. The
      quality of the scan was good or very good in 42 patients (mean GFR = 92
      ml/min/1.73 m2 SA) and moderate or poor in nine patients (median GFR = 20
      ml/min/1.73 m2 SA) (P < 0.001). A residual urine was noted following micturition
      in 35 boys; this was due to incomplete bladder emptying in 14 and to immediate
      secondary refilling from dilated upper tracts in the remainder. CONCLUSION: IRC
      in conjunction with traditional dynamic renography using MAG 3 provides valuable
      additional information about upper tract drainage. The necessity for diuresis
      renography is obviated in the majority of patients. IRC also allows an excellent
      non-invasive, physiological assessment of both upper and lower urinary tract
      function which is superior to conventional single examination techniques. We
      recommend the use of MAG 3 with IRC in the routine follow-up of boys with
      posterior urethral valves.

PMID- 7827853
TI  - Long-term results of intermittent low-friction self-catheterization in patients
      with recurrent urethral strictures.
AB  - OBJECTIVE: To ascertain the duration of intermittent low-friction self
      catheterization (ILSC) required to cause stricture stabilization. PATIENTS AND
      METHODS: Over a 4 year period, 101 patients with a median age of 62 years (range
      16-85) with recurrent urethral strictures were recruited to the trial. All the
      strictures were treated by internal urethrotomy and the patients were then
      randomized to perform ILSC twice weekly for either 6 months (group 1) or 36
      months (group 2). Out-patient follow-up with urinary flow rate was initially at 1
      month and then at 3 monthly intervals. Stricture recurrence rates were compared
      between the two groups. RESULTS: Of 101 patients, seven failed to attend after
      the first out-patient appointment. A further 21 died of unrelated disease whilst
      on ILSC (although 13 had been followed up for at least 24 months and so were
      included in the analysis). The median follow-up was 67 months (range 24-78). Ten
      patients in group 2, who had suffered from recurrent strictures, refused to stop
      catheterizing at the appointed time and all remain stricture-free on permanent
      ILSC. Of the remaining 76 patients, 48 catheterized for 6 months and 28 patients
      performed ILSC for 12 to 36 months (nine stopped earlier than intended). Forty
      per cent of patients who stopped at 6 months developed a recurrence compared with
      14% who catheterized for more than 12 months (P < 0.05) (chi-square test with
      Yates' correction). CONCLUSIONS: Our results indicate that ILSC is safe and
      effective in preventing stricture recurrence in the long term. The recurrence
      rate of urethral strictures was significantly lower when ILSC was continued for
      more than 12 months compared with ILSC that was stopped at 6 months. We conclude
      that catheterization for at least 1 year is required to achieve adequate urethral
      stabilization.

PMID- 7827854
TI  - Laparoscopic orchidopexy: a simple technique for establishing the abdominoscrotal
      port.

PMID- 7827855
TI  - Percutaneous cystoscopy assisted urethral synechiotomy: a method to obtain an
      antegrade urethrogram in traumatic urethral stricture.

PMID- 7827856
TI  - A fatal case of severe haemorrhagic cystitis associated with malakoplakia.

PMID- 7827857
TI  - Solitary fibrous tumour of the spermatic cord.

PMID- 7827858
TI  - Soft tissue metastasis from a renal cell carcinoma.

PMID- 7827859
TI  - Concurrent malakoplakia and primary squamous cell carcinoma arising in long
      standing chronic cystitis.

PMID- 7827860
TI  - Recurrent lichen sclerosus et atrophicus in urethroplasties from multiple skin
      grafts.

PMID- 7827861
TI  - Scrotal scintigraphy in bilateral adolescent testicular torsion.

PMID- 7827862
TI  - Blast trauma and testicular rupture: an unusual civilian injury.

PMID- 7827863
TI  - Renal vein thrombosis caused by primary antiphospholipid syndrome.

PMID- 7827864
TI  - Seminal emission following exposure to cold stimulation: bizarre complication in
      the chronic stage of cord infarction.

PMID- 7827865
TI  - An unusual double pigtail stent story.

PMID- 7827866
TI  - Evaluation of grafts for occult tumor cells.

PMID- 7827867
TI  - Detection of tumor contamination of peripheral stem cells in patients with
      lymphoma using cell culture and polymerase chain reaction technology.
AB  - The important question of whether residual tumor in the bone marrow or peripheral
      blood stem cell graft contributes to relapse in autologous bone marrow
      transplantation in patients with non-Hodgkin's lymphoma can be addressed only if
      there is an accurate and sensitive measurement of tumor cell contamination of the
      graft. Assays utilizing DNA amplification based on the polymerase chain reaction
      (PCR) are highly sensitive. Tumor-specific primers and probes can be designed for
      the clonally rearranged Ig or T cell antigen receptor genes in the original
      tumors, and these can then be used to detect minimal residual disease in
      subsequent specimens. Specific translocations can also be exploited as tumor
      markers, and the t(14;18) translocation has been widely employed for detecting
      tumor cells in blood and bone marrow samples. Lymphoma cells have also been grown
      successfully in tissue culture, and the detection of tumor contamination of
      autologous grafts has been associated with a poorer prognosis in patients with
      intermediate- or high-grade lymphoma. It is of interest to compare the
      sensitivity of tumor detection and the predictive value for patient survival of
      the PCR-based and culture-based assays. The information obtained may help to
      determine whether minimal tumor contamination of an autologous graft is
      clinically significant and, if so, the assay(s) that should be employed.

PMID- 7827868
TI  - Bone marrow purging in acute lymphoblastic leukemia: biological and clinical
      features.
AB  - A group of 56 patients with immunophenotyped acute lymphoblastic leukemia had
      their bone marrow purged using monoclonal antibody (MAb) and complement.
      Mononuclear marrow cells were treated with panels of MAb directed against T cells
      (n = 19), CD10-CALLA (n = 16), and B cells (n = 21), resulting in median specific
      cell depletions of 96.50, 97.59, and 96.97%, respectively. The resulting CFU-GM
      recoveries were 60.15, 110.6, and 72.9%. Long-term bone marrow cultures showed
      normal formation of adherent cell layers in 17 of 23 cases, and failure to form
      an adherent layer correlated with poor hematological reconstitution. A total of
      32 patients (aged 4-40 years) received purged marrow grafts containing a median
      of 1.32 x 10(7) mononuclear cells/kg and 1.64 x 10(4) CFU-GM/kg; 7 patients
      required backup marrow. Time to engraftment of 500 granulocytes, 1000 leukocytes,
      20,000 platelets, and 50,000 platelets was 37, 38, 39, and 57 days, respectively.
      A total of 16 patients (50%) remain alive and in complete remission 313-913 days
      posttransplant (median 565 days); 13 patients (41%) relapsed between 50 and 365
      days posttransplant (median 100 days), and 3 patients (9%) died from transplant
      associated complications.

PMID- 7827869
TI  - Future paradigm for autologous bone marrow transplantation: tumor purging and ex
      vivo production of normal stem and progenitor cells.
AB  - A major concern in autologous bone marrow transplantation (ABMT) is the possible
      contamination of the graft with tumor cells. Transplantation of malignant cells,
      along with normal hematopoietic stem and progenitor cells, may contribute to
      relapse of disease. Therefore, a growing strategy is to subject autologous marrow
      to some type of purging procedure to eliminate tumor cells selectively.
      Transplantation of purged marrow, however, often results in a delayed engraftment
      associated with (specific or nonspecific) loss of normal stem and progenitor
      cells during manipulations related to the purging process. A new and burgeoning
      field in the area of clinical bone marrow transplantation is the ex vivo
      production of stem and progenitor cells. Several advantages accrue to this
      strategy. First, this technology makes it possible to expand the stem and
      progenitor cell population of a small volume of bone marrow or mobilized
      peripheral blood (MPB), thus lessening the initial tumor burden to be purged.
      Secondly, ex vivo marrow or MPB expansion may overcome the significant problem of
      delayed engraftment by rebuilding the numbers of normal stem and progenitor cells
      necessary for both early and durable engraftment. To accomplish these and other
      objectives, an automated and closed, clinical-scale bioreactor system, based on
      continuous perfusion technology, is being developed and will soon enter clinical
      trials.

PMID- 7827870
TI  - Reversal of multidrug resistance.

PMID- 7827871
TI  - Inadequate red cell depletion of large-volume marrow harvests processed on the
      Fenwal CS-3000 Plus.
AB  - In this report we describe a procedure for the depletion of erythrocytes in bone
      marrow harvests using the Fenwal CS-3000 Plus cell separator. In a study of 15
      consecutive harvests, adequate red cell depletion could not be achieved with
      large-volume marrows with > 500 ml erythrocytes.

PMID- 7827872
TI  - Bone marrow transplantation in leukemia.
AB  - Bone marrow transplants are increasingly being used as treatment for leukemia.
      Several IBMTR studies have identified variables predicting outcome in allogeneic
      transplants. These studies have also identified factors like GVL that increase
      our understanding of leukemia treatment. Following the success of HLA-identical
      sibling transplants, allografts from related and unrelated donors are now
      performed frequently and achieve long-term LFS. The use of autologous
      transplants, with and without marrow treatment, is also increasing and continues
      to be investigated as an alternative therapy for leukemia.

PMID- 7827873
TI  - Bone marrow transplantation in the management of acquired aplastic anemia.

PMID- 7827874
TI  - Repeat resection of recurrent hepatic colorectal metastases.

PMID- 7827875
TI  - Complications of thyroidectomy.

PMID- 7827876
TI  - Iodized oil in the treatment of hepatocellular carcinoma.
AB  - When injected into the hepatic artery the contrast agent Lipiodol (iodized poppy
      seed oil) is selectively retained by hepatocellular carcinoma (HCC) for a
      prolonged period of time. Liver computed tomography (CT) performed after Lipiodol
      angiography is more sensitive than ordinary CT at imaging HCC. Arterial
      administration of cytotoxic drugs and radioisotopes conjugated to Lipiodol has
      been shown to be reasonably safe in patients with irresectable HCC. These
      therapies, often combined with embolization, provide effective palliation, better
      tumour response and improved survival compared with other available treatments.
      Their use as a preoperative adjunct to surgical resection of HCC is
      controversial.

PMID- 7827877
TI  - Penetrating cardiac injuries: clinical classification and management strategy.
AB  - The management of penetrating cardiac injury is controversial. To facilitate
      decision making, a simple clinical classification of patients with such an injury
      is proposed. Five categories are considered: (1) lifeless, (2) critically
      unstable, (3) cardiac tamponade, (4) thoracoabdominal injury and (5) benign
      presentation. Investigation, if indicated, and the timing and setting of surgical
      intervention are discussed for each category.

PMID- 7827878
TI  - Molecular and cellular basis of cancer invasion and metastasis: implications for
      treatment.
AB  - In the past decade significant advances in establishing the underlying biological
      mechanisms of tumour invasion and metastasis have been made. Some of the
      triggering factors and genes relevant to metastatic spread have been identified.
      Advances have also been made in understanding the signal transduction pathways
      involved in invasion and metastasis. This increased comprehension of the
      malignant metastatic process has enabled new antimetastatic strategies to be
      devised. This review summarizes progress in these areas and discusses the
      implications for the treatment of metastasis.

PMID- 7827879
TI  - Duplex ultrasonography for assessment of venous valvular function of the lower
      limb.
AB  - Both legs of 29 patients with venous disease and those of 15 controls without
      venous disease were assessed by duplex ultrasonography. The duration of reverse
      flow after release of manual calf compression was measured in the common femoral,
      long saphenous, popliteal and short saphenous veins. Before undertaking the
      study, the reproducibility of the technique was evaluated in six subjects by
      repeating the examination over 3 consecutive days; the coefficient of variation
      of the test was 7.3 per cent. The 95 per cent confidence interval (c.i.) of the
      median (0.16 s) of all measurements in the normal limbs was 0.12-0.18 s. The 95
      per cent c.i. for the 95th percentile of all measurements in normal limbs was
      0.32-0.52 s. In limbs with clinical evidence of venous disease at least one of
      the sites examined was found to have reverse flow lasting longer than 0.5 s.
      These data suggest that the measurement of reverse flow after release of manual
      calf compression is a reproducible technique. While the method records some
      reverse flow in normal veins, its duration is unlikely to exceed 0.5 s;
      significant reflux is therefore defined as reverse flow exceeding 0.5 s.

PMID- 7827880
TI  - Rehabilitation outcome 5 years after 100 lower-limb amputations.
AB  - Received wisdom commends a policy of maximizing the ratio of below-knee to above
      knee amputations in patients with end-stage arterial disease. After adoption of
      this policy, the long-term outcome of 100 consecutive lower-limb amputations in
      96 patients was monitored by annual review for 5 years. The ratio of primary
      below-knee to above-knee amputations was 2:1, with 9 per cent of below-knee
      amputations undergoing revision to a higher level. At 2 years after amputation
      only 26 per cent of patients were successfully walking out of doors, while 40 per
      cent had died. By 5 years 67 per cent were dead and only 9 per cent continued to
      walk out of doors with an artificial limb, although a further 8 per cent
      continued to use the limb within the confines of their own homes. In a previous
      audit of 193 amputations performed during the 3.5 years to December 1984, stump
      healing was a problem in 45 per cent of primary below-knee amputations, compared
      with 25 per cent in the present study. Although the below- to above-knee ratio in
      1984 was only 1:2, the overall rehabilitation rate, as determined by the
      proportion of patients able to walk at 2 years, was 34 per cent. It is concluded
      that increasing the proportion of below-knee amputations from one-third to two
      thirds of lower-limb amputations for occlusive arterial disease does not improve
      effective rehabilitation rates. Received wisdom on the desirability of a high
      below- to above-knee ratio may be wrong.

PMID- 7827881
TI  - Epidemiology of leg amputation: the influence of vascular surgery.
AB  - The number of amputations performed for vascular disease in Denmark has decreased
      from 1777 (34.5 per 100,000 population) in 1983 to 1288 (25.0 per 100,000) in
      1990, a reduction of 28 per cent. This decline coincided with an increase in
      vascular surgical activity of up to 100 per cent, including a marked rise in the
      rate of femorodistal reconstruction. Moreover, regional variation in vascular
      surgical activity correlated with percentage reduction in amputation rate (rS =
      0.65, P < 0.01). The relative number of above-knee amputations also decreased in
      favour of more distal levels during the period studied. These findings suggest
      that vascular surgery may be responsible for the lower amputation rate.

PMID- 7827882
TI  - Right atrial electrocardiography: a technique for the placement of central venous
      catheters for chemotherapy or intravenous nutrition.
AB  - Central venous catheters used for chemotherapy are usually sited so that the
      catheter tip lies in the superior vena cava. This study evaluated right atrial
      electrocardiography as a method of accurately placing the catheter tip in 34
      patients over a period of 22 months. An electrocardiograph adaptor was connected
      to the catheter and the tip advanced into a central vein until a biphasic P wave
      was identified. In 31 of 34 patients the characteristic P wave changes were
      observed and the position of the catheter tip confirmed by screening to be in the
      superior vena cava. Right atrial electrocardiography is an accurate, reliable and
      rapid method of positioning the tip of a central venous catheter, and avoids or
      reduces exposure to radiation.

PMID- 7827883
TI  - Closure of midline laparotomy incisions with polydioxanone and nylon: the
      importance of suture technique.
AB  - The healing of midline laparotomy incisions closed with a continuous suture of
      nylon or second-generation polydioxanone was evaluated in a randomized clinical
      trial. The effect of suture technique, reflected in the suture length to wound
      length ratio, was also assessed. All patients who underwent abdominal surgery
      through a midline incision were included except those with incisional hernia
      after previous midline operation. Wound dehiscence occurred in five (0.6 per
      cent) of 813 patients and wound infection in 73 (9.0 per cent). These rates were
      similar for both suture materials, as were those for the development of suture
      sinus and prolonged postoperative wound pain. Incisional hernia 12 months after
      surgery was found in 49 (15.1 per cent) of 325 wounds sutured with polydioxanone
      and in 50 (15.7 per cent) of 318 closed with nylon (P = 0.91). There was a
      significant correlation between the hernia rate and the suture to wound length
      ratio for both materials (P < 0.001). These results indicate that suture of
      midline laparotomy wounds is as safe with polydioxanone as it is with nylon.
      Incisional hernia is associated more with suture technique than with the material
      used.

PMID- 7827884
TI  - Blood flow measurement in extremity soft tissue sarcoma with technetium-99m
      hexamethyl-propyleneamineoxime and single photon emission computed tomography.
AB  - Blood flow measurements were made in 28 patients with soft tissue sarcoma of the
      extremities to investigate the prognostic significance of tumour vascularity.
      Four patients with benign tumours also underwent blood flow measurement. Mean and
      maximum tumour blood flow was calculated from technetium-99m hexamethyl
      propyleneamineoxime uptake measured using single photon emission computed
      tomography (SPECT), tumour volume measured from SPECT transaxial image
      reconstructions and cardiac output assessed with Doppler ultrasonography. Twenty
      seven malignant lesions and one benign tumour showed increased uptake of isotope
      relative to surrounding tissues. Mean sarcoma blood flow varied between 1 and 33
      ml per 100 ml tumour per min, and maximum flow between 5 and 57 ml per 100 ml per
      min. Fourteen patients developed progressive disease during the first year of
      follow-up. Eight of 11 patients with a high isotope uptake ratio, eight of 12
      with a high mean blood flow and eight of 14 with a high maximum blood flow
      relative to the respective medians for the series showed disease progression.

PMID- 7827885
TI  - Multifocal nature of adenolymphoma of the parotid.
AB  - The multifocal nature of adenolymphoma of the parotid salivary gland was studied
      in 24 patients who underwent parotidectomy. Twenty-six resected specimens were
      examined by a step-serial whole-organ sectioning technique; multiple
      adenolymphoma was found in 13. The maximum number of synchronous tumours in any
      gland was four. Salivary epithelial elements were found embedded within lymph
      nodes in nine resected specimens. Synchronous or metachronous bilateral tumours
      were found in eight patients. The multifocal nature of adenolymphoma of the
      parotid gland is demonstrated.

PMID- 7827886
TI  - Intraoperative assessment of nodal status in the selection of patients with
      breast cancer for axillary clearance.
AB  - Axillary node status was assessed by intraoperative contact cytology of four
      sampled nodes in each of 114 consecutive patients with operable breast cancer
      treated by wide local excision or mastectomy. At a mean follow-up of 18.7 months,
      43 node-positive patients who underwent immediate axillary clearance had two
      locoregional and six distant recurrences with two deaths; four had arm oedema and
      one shoulder stiffness. There were no recurrences or arm and shoulder morbidity
      in 71 node-negative women who had no clearance or radiotherapy. The mean hospital
      stay was 4.3 days for patients having wide local excision versus 7.2 days for
      those undergoing excision and axillary clearance (P < 0.001), and 8.9 days for
      patients receiving a mastectomy versus 9.1 days for those having mastectomy and
      clearance (P not significant). Selective axillary clearance based on
      intraoperative contact cytology of four sampled nodes reduces hospital stay in
      patients treated by wide local excision and may lead to a reduction in arm
      morbidity without impairing disease control.

PMID- 7827887
TI  - Interstitial laser photocoagulation as a treatment for breast cancer.
AB  - This preliminary report describes the use of interstitial laser photocoagulation
      to manage small breast cancers. Forty-four patients were treated with a diode
      laser of 805 nm under local anaesthesia in the interval between diagnosis and
      surgery. Ultrasonography was used in 42 patients and computed tomography (CT) in
      two to place the fibre in the tumour and monitor laser effects. Laser-induced
      necrosis within the resected tumour varied from 0 to 25 mm in diameter. The
      presence of charring in the tumour around the fibre tip after treatment was
      associated with significantly larger diameters of necrosis than when charring did
      not occur (median 13 versus 6 mm, P = 0.002). Precharring the fibre resulted in a
      more predictable diameter of necrosis (median 14 mm). Ultrasonography was
      inaccurate in assessing laser damage; dynamic CT and magnetic resonance imaging
      may be of more use. Interstitial laser photocoagulation is simple and safe, and
      can produce necrosis of a reasonably predictable extent.

PMID- 7827888
TI  - Two-team synchronous oesophagectomy.
AB  - Between 1984 and 1992, 131 patients underwent two-team synchronous oesophagectomy
      for carcinoma. Some 95 per cent of tumours were successfully resected by this
      technique. In 5 per cent of patients the tumour was found to be irresectable at
      operation and gastric bypass was performed. The overall operative mortality rate
      was 8 per cent and the pulmonary complication rate 10 per cent. The actuarial
      survival rate was 55 per cent at 1 year, 22 per cent at 3 years and 16 per cent
      at 5 years. When compared with the traditional two-stage Lewis approach, two-team
      synchronous oesophagectomy was significantly faster (mean 222 versus 282 min),
      but was not significantly different with respect to blood loss, transfusion
      requirement, pulmonary complications or operative mortality rate. Patients
      undergoing two-team oesophagectomy had a significantly shorter hospital stay than
      those receiving the two-stage procedure (mean 16 versus 24 days).

PMID- 7827889
TI  - Expression of p53 protein in oesophageal carcinoma: clinicopathological
      correlation and prognostic significance.
AB  - Correlation of p53 expression with 5-year survival and histopathological
      parameters was examined immunohistochemically in two groups of 30 patients with
      oesophageal carcinoma (5-year survivors versus non-survivors). Tumour type, sex,
      operative procedure and age were matched. Some 64 per cent of squamous carcinomas
      and 79 per cent of adenocarcinomas were p53 positive. Normal squamous, normal
      glandular and metaplastic glandular epithelia were negative. Dysplastic squamous
      and glandular epithelium adjacent to tumours was positive when the tumour was
      positive and negative when it was not. Univariate analysis showed that nodal
      status (P = 0.001), and grade and depth of invasion (both P = 0.01) correlated
      with outcome. Correlation of tumour grade with outcome, when the most poorly
      differentiated area is used, is a novel finding for oesophageal carcinoma. The
      p53 status was not significantly associated with survival or any of these
      parameters.

PMID- 7827890
TI  - Classification of the sequelae of bowel resection for Crohn's disease.
AB  - A postoperative handicap index designed to predict diarrhoea and malnutrition
      following bowel resection in patients with Crohn's disease is proposed. The index
      takes into account the location and extent of resection, and its value can be
      calculated from operative records. Retrospective (n = 218) and prospective (n =
      68) series of patients were studied. Diarrhoea and malnutrition developed in 102
      patients (47 per cent) and 13 patients (6 per cent) respectively in the
      retrospective series, and in 40 (59 per cent) and one (1 per cent) of those in
      the prospective series. The handicap index correlated with faecal weight and
      faecal fat in 112 patients tested. Positive and negative predictive values of an
      index score greater than 20 for the development of diarrhoea, and over 50 for the
      development of malnutrition, were 0.64 and 0.90, and 0.60 and 0.99 respectively
      in the retrospective series; values were 0.80 and 0.71, and 0.25 and 1.00 in the
      prospective series. The postoperative handicap index is a useful tool for
      predicting the functional consequences of bowel resection for Crohn's disease.

PMID- 7827891
TI  - Chronic obscure groin pain is commonly caused by enthesopathy: 'tennis elbow' of
      the groin.
AB  - Forty-nine patients with chronic obscure groin pain, bilateral in four, presented
      to one general surgeon in a 12-month period. Inflammation ('enthesopathy') at the
      pubic insertion of the inguinal ligament was the cause in 30 patients (32
      groins). This has not previously been recognized as a cause of chronic groin
      pain, possibly because the exact site of tenderness can be obscured by the pubic
      pad of fat. Enthesopathy also occurred in five rectus and one adductor longus
      tendons (one patient had inflammation in both). Infiltration with long-acting
      steroid (1 per cent triamcinolone) and local anaesthetic (2 per cent lignocaine)
      was offered to all patients with localized tenderness of tendon or ligament. A
      questionnaire survey 3-15 months after injection showed a better outcome after
      treatment than when injection was declined. Other causes of pain included nerve
      entrapment (five cases), spinal referred pain (five in four patients) and
      ureteric stones (two). Inguinal hernia is sometimes coincidental rather than
      causative of the pain. In three patients the pain had subsided and no diagnosis
      was made. Simple diagnostic and therapeutic measures may relieve chronic groin
      pain and spare patients elaborate investigation or unnecessary operation.

PMID- 7827892
TI  - Portal vein resection in patients undergoing pancreatoduodenectomy for carcinoma
      of the pancreatic head.
AB  - Of 176 patients with carcinoma of the pancreatic head region 156 underwent
      standard pancreatoduodenectomy (group 2) and 20 with macroscopic suspicion of
      invasion of the portal vein or superior mesenteric vein (SMV) underwent
      pancreatoduodenectomy with partial resection of the portal vein or SMV (group 1).
      In 16 patients in group 1 end-to-end anastomosis was used for reconstruction of
      the vein. The morbidity rate in groups 1 and 2 was similar (55 versus 63 per
      cent). The hospital mortality rate was 15 per cent in group 1 and 7 per cent in
      group 2 (P = 0.22). Histological examination confirmed tumour invasion of the
      portal vein or SMV in ten patients in group 1. Invasion of the portal vein or SMV
      was significantly more frequent in patients with pancreatic cancer than in those
      with distal bile duct or ampullary carcinoma. Of the 20 patients in group 1 only
      three underwent curative resection with tumour-free margins. The median survival
      time after resection of the portal vein or SMV was 8 months; the 2-year survival
      rate was 19 per cent. Comparison of survival in group 1 with survival in
      subgroups of patients undergoing standard pancreatoduodenectomy, matched for all
      histological parameters, showed no significant difference. It is concluded that
      partial resection of the portal vein or SMV in patients undergoing
      pancreatoduodenectomy who are suspected of having tumour invasion of the portal
      vein or SMV does not improve either the rate of curative resection or survival.

PMID- 7827893
TI  - Laparoscopic surgery in patients with human immunodeficiency virus.
AB  - Fifteen patients with acquired immune deficiency syndrome (AIDS), and one who
      tested positive for human immunodeficiency virus but had no AIDS-defining
      diagnosis, underwent a range of laparoscopic procedures between March 1991 and
      March 1993. Seven cholecystectomies and one cholecystojejunostomy were performed.
      Three patients underwent diagnostic laparoscopy after presenting with abdominal
      emergencies. Two further patients had laparoscopic adhesiolysis and one
      appendicectomy. A further patient underwent laparoscopically assisted end
      colostomy and another an inguinal hernia repair, both performed electively. Two
      patients died in the postoperative period. There was little postoperative
      morbidity. Six patients died 3-18 months after surgery from progressive AIDS.
      This early experience suggests that laparoscopic surgery is well tolerated in
      these patients.

PMID- 7827894
TI  - Gallbladder disease related to human immunodeficiency virus infection:
      presentation and surgical management.

PMID- 7827895
TI  - Delayed diagnosis of malignant tumours missed at laparoscopic cholecystectomy.

PMID- 7827896
TI  - Laparoscopic cholecystectomy for acute cholecystitis.
AB  - The safety and efficacy of laparoscopic cholecystectomy for acute cholecystitis
      were evaluated in a 2-year retrospective review. Results of laparoscopic
      cholecystectomy in 66 patients with acute inflammation of the gallbladder were
      compared with those of the standard open procedure for this condition (43
      patients) and routine laparoscopic cholecystectomy (227 patients). The
      laparoscopic procedure for acute cholecystitis was successful in 46 of 66
      patients. There was no difference in mean operating time when the inflamed
      gallbladder was removed laparoscopically or at open surgery (82 versus 84 min);
      however, each procedure took longer than did routine laparoscopic cholecystectomy
      (mean 69 min; P < 0.01). There was no difference in analgesic requirement between
      patients who underwent laparoscopic removal of an acutely inflamed gallbladder
      and those in the other two groups. Postoperative recovery was significantly
      faster than that after open surgery (P < 0.01), but took longer than that
      following routine laparoscopic cholecystectomy (P < 0.01). Inability to identify
      the cystic duct was the most common reason for conversion to open operation,
      which occurred in 20 cases of acute cholecystitis. Bile duct injury occurred in
      one of 66 patients with acute cholecystitis treated laparoscopically, two of 227
      cases of routine laparoscopic cholecystectomy but in no patient who underwent
      open cholecystectomy. In conclusion, laparoscopic cholecystectomy is technically
      achievable in the majority of patients with acute cholecystitis. The conversion
      rate is high but, if the procedure is completed successfully, postoperative
      recovery is more rapid than that after open surgery. However, the method carries
      a higher incidence of complications and should be attempted only by experienced
      surgeons.

PMID- 7827897
TI  - Survival after surgery for cancer of the gallbladder.
AB  - The records of 45 patients with carcinoma of the gallbladder who had undergone
      surgical resection at least 5 years previously were reviewed retrospectively to
      determine which factors influence long-term survival. Seventeen patients survived
      at least 5 years and 23 died from recurrence (five patients were excluded from
      analysis). Of the 17 long-term survivors 15 had tumours superficial to the
      subserosa that showed a non-infiltrative growth pattern. Those alive at 5 years
      were more likely than short-term survivors to have tumours that were papillary (P
      < 0.05) or well differentiated (P < 0.01) adenocarcinoma. Venous, lymphatic and
      perineural invasion was more common in short- than in long-term survivors (87
      versus 29 per cent, P < 0.001). Patients with tumours limited to the muscularis
      and those with non-infiltrative subserosal involvement are likely to have better
      survival and may have a chance of cure after extended cholecystectomy.

PMID- 7827898
TI  - Carcinoid tumour presenting with caecal infarction.

PMID- 7827899
TI  - Colocutaneous fistula between the sigmoid colon and popliteal fossa in
      diverticular disease.

PMID- 7827900
TI  - Impact of intraoperative ultrasonography on treatment strategy for colorectal
      cancer.
AB  - The impact of intraoperative ultrasonography (IOUS) on treatment strategy was
      studied in 122 patients with primary colorectal cancer. All patients underwent
      preoperative liver imaging by ultrasonography and computed tomography (CT). After
      curative resection of the primary tumour patients were eligible for adjuvant
      chemotherapy. The findings on IOUS were assessed by ultrasonography 6 months
      after laparotomy. Of 34 patients with suspected liver metastases on
      ultrasonography or CT, the diagnosis was confirmed by IOUS in 21. In the
      remaining 13 patients the suspect lesions were shown to be benign. Of the 88
      patients with normal preoperative imaging results, suspect lesions were detected
      in five; in four the lesion was found by IOUS only. One of these four also had an
      extrahepatic metastasis. At follow-up the diagnosis of metastasis proved to be
      wrong in two of the remaining three patients, so IOUS was helpful in only one
      patient. Surgical management was not markedly influenced by findings on IOUS in
      any patient. However, IOUS correctly changed the stage of the disease, and
      consequently postoperative treatment, in 14 patients (11 per cent). Two patients
      were erroneously excluded from the adjuvant protocol following an incorrect
      diagnosis based on IOUS.

PMID- 7827901
TI  - Endoscopic surveillance for colorectal neoplasia.

PMID- 7827902
TI  - Clinical value of whole-body positron emission tomography with
      [18F]fluorodeoxyglucose in recurrent colorectal cancer.
AB  - To assess the clinical value of whole-body positron emission tomography (PET)
      with [18F]fluorodeoxyglucose (FDG) in recurrent colorectal cancer, 35 patients
      were studied: 15 had resectable liver metastases, one a resectable lung
      metastasis, eight resectable pelvic recurrence, eight a presacral mass with
      equivocal findings on imaging, and three increasing serum levels of
      carcinoembryonic antigen (CEA) without clinical or radiological signs of
      recurrent disease. PET affected management decisions in seven of 16 patients with
      metastatic disease. In one of eight patients with pelvic recurrence demonstrated
      by computed tomography (CT), PET detected unknown pulmonary metastases. In five
      of eight presacral masses with equivocal CT findings, PET was correct and
      unexpected distant metastases were detected in one of these patients. In two of
      three patients with increasing CEA levels and normal pelvic CT findings, pelvic
      recurrence was identified. Overall, whole-body PET affected management in 14
      patients. PET is a valuable tool for staging local recurrence and metastatic
      disease.

PMID- 7827903
TI  - Flexible sigmoidoscopy in addition to contrast enema in the diagnosis of left
      sided large bowel obstruction.

PMID- 7827904
TI  - The AXIS colorectal cancer trial: randomization of over 2000 patients. The AXIS
      Steering Group.

PMID- 7827905
TI  - Prospective randomized trial of mechanical bowel preparation in patients
      undergoing elective colorectal surgery.
AB  - A total of 149 patients admitted for elective colorectal surgery were randomly
      allocated to receive preoperative mechanical bowel preparation (group 1) or no
      mechanical bowel preparation (group 2). All patients received antimicrobial
      prophylaxis with cephalothin and metronidazole. The overall incidence of wound
      infection was 17.4 per cent (24 per cent for group 1, 12 per cent for group 2)
      and that of dehiscence 7.4 per cent (10 per cent for group 1, 5 per cent for
      group 2). The incidence of wound infection was significantly higher in group 1 (P
      < 0.05) but that of anastomotic dehiscence did not differ significantly between
      groups. Mechanical bowel preparation is unnecessary and may be harmful in terms
      of preventing wound infection and anastomotic dehiscence in patients undergoing
      elective colorectal surgery.

PMID- 7827906
TI  - Experimental colonic healing in relation to timing of 5-fluorouracil therapy.
AB  - In an experimental study resembling clinical use of adjuvant 5-fluorouracil (5
      FU) treatment of colorectal carcinoma, 97 male Wistar rats were operated on with
      a standardized left colonic resection. Treatment was given as a daily
      intraperitoneal injection. The animals were randomized to one of four groups:
      early treatment with 5-FU 20 mg/kg or saline 0.1 mol/l from the day of operation
      to day 7 after operation, and delayed treatment with 5-FU 20 mg/kg or saline 0.1
      mol/l from the third day after operation to the day before killing. The animals
      were killed in groups on day 7 or 10 after operation. In the group receiving
      early 5-FU treatment there was an increased rate of anastomotic complications
      (seven of 26) compared with none in the control or delayed 5-FU groups. The
      anastomotic breaking strength in animals having early 5-FU treatment (day 7,
      median 1.45 (range 0.20-2.95) N; day 10, median 1.80 (range 0.95-3.20) N) was
      significantly lower than that in controls on both day 7 (median 3.20 (range 2.50
      3.80)N) and day 10 (median 3.20 (range 2.20-3.60)N). In the delayed 5-FU
      treatment group anastomotic breaking strength did not differ from that in
      controls. Colonic healing was not impaired when intraperitoneal 5-FU treatment
      was started on day 3 after operation, whereas immediate postoperative
      administration of 5-FU had a detrimental effect on wound healing.

PMID- 7827907
TI  - Delorme operation for rectal prolapse.
AB  - A consecutive series of 49 elderly patients of mean age 73 years with full
      thickness rectal prolapse underwent the Delorme operation between 1986 and 1990.
      A standard technique was used, or supervised, by one surgeon. In this prospective
      series, 43 patients were reviewed clinically. The Delorme operation abolished
      rectal prolapse in 32 patients. Half of the 40 with faecal incontinence were
      rendered continent. Failure was related to previous anorectal surgery and/or
      psychiatric illness. Of the 11 patients in whom the first procedure failed, four
      were improved by a second Delorme operation. The Delorme operation is a suitable
      procedure for elderly and/or medically unfit patients with rectal prolapse. Good
      results have also been demonstrated for younger patients, suggesting that the
      operation may have wider application.

PMID- 7827908
TI  - Motor abnormalities in the terminal ileum of patients with chronic idiopathic
      constipation.
AB  - Abnormalities in oesophageal, gastric and jejunal motility have been described in
      patients with chronic idiopathic constipation, suggesting that this may be a
      panenteric disorder. To test the hypothesis that ileal motility is also abnormal
      in constipation, terminal ileal motility was studied in ten patients and six
      healthy controls by prolonged and ambulant manometry. Mean(s.e.m.) phase II
      activity was significantly prolonged in patients compared with controls, during
      wakefulness (61.6(7.3) versus 19.3(3.5) per cent, P < 0.001) and sleep (44.4(9.0)
      versus 1.1(0.8) per cent, P < 0.001). The mean(s.e.m.) duration of phase III
      fronts was shorter in patients (7.9(1.8) min) than in controls (13.2(1.3) min; P
      < 0.001). Retrograde propagation was seen in approximately 15 per cent of all
      phase IIIs in patients but not in control subjects. The mean(s.e.m.) duration of
      postprandial activity was significantly shorter in patients than in controls
      (30.1(6.2) versus 130.0(68.0) min, P < 0.001). Ileal motility is abnormal in
      patients with chronic idiopathic constipation. This may result from an
      abnormality of the enteric nervous system or abnormal modulation of this system
      by the central nervous system.

PMID- 7827909
TI  - Effect of age, sex and parity on anorectal function.
AB  - Ninety-one healthy subjects (51 women; age range 16-85 years) were studied
      prospectively to determine the effect of age, sex and parity on anorectal
      function. Maximum resting pressure, voluntary contraction pressure, rectal
      sensation to distension, rectal and mid-anal electrosensitivity, perineal
      descent, pudendal nerve terminal motor latency and fibre density of the external
      and sphincter were measured. Sex influenced mean(s.d.) voluntary contraction
      pressure (148(56) versus 95(43) cmH2O for men versus women, P < 0.0001), perineal
      descent on straining (1.0(0.5) versus 1.3(0.4) cm, P = 0.02) and fibre density
      (1.43(0.14) versus 1.52(0.15), P = 0.02). Age influenced resting pressure (r = 
      0.43, P = 0.0001), perineal position at rest (r = -0.55, P < or = 0.0001), mid
      anal electrosensitivity (r = 0.42, P = 0.0001) and rectal electrosensitivity (r =
      0.54, P < 0.0001). Parity affected mean(s.d.) voluntary contraction pressure
      (105(53) versus 75(20) cmH2O for nulliparous versus parous women, P = 0.04) and
      mid-anal electrosensitivity (5.3(2.3) versus 4.5(2.3) mA, P = 0.02). Increasing
      age leads to perineal descent at rest, slowed pudendal nerve conduction, a fall
      in resting anal pressure and decreased anorectal sensory function. Women have a
      lower and squeeze pressure, greater perineal descent, longer pudendal nerve
      terminal motor latency and a greater muscle fibre density than men. Parity leads
      only to lower squeeze pressure.

PMID- 7827910
TI  - Management of bile duct stones in the era of laparoscopic cholecystectomy.

PMID- 7827911
TI  - Perioperative and postoperative tranexamic acid reduces the local wound
      complication rate after surgery for breast cancer.

PMID- 7827912
TI  - Laparoscopic cholecystectomy for biliary pancreatitis.

PMID- 7827913
TI  - Elbow arteriovenous fistulas for chronic haemodialysis.

PMID- 7827914
TI  - Timing of extubation after oesophagectomy.

PMID- 7827915
TI  - Severe myonecrosis following laparoscopy for ovarian surgery.

PMID- 7827916
TI  - Abdominal wall metastases following laparoscopy.

PMID- 7827917
TI  - Multicentre audit of death from acute pancreatitis.

PMID- 7827918
TI  - Variation in outcome of surgical procedures.

PMID- 7827919
TI  - Radical resection for ampullary carcinoma: long-term results.

PMID- 7827920
TI  - Smoking, nitric oxide and the endothelium.

PMID- 7827921
TI  - Combined laparoscopic and endoscopic treatment of gallstones and bile duct
      stones: a prospective study.

PMID- 7827922
TI  - Arterial embolectomy: a century and out.

PMID- 7827923
TI  - Infection and acute pancreatitis.

PMID- 7827924
TI  - Virtual reality and laparoscopic surgery.
AB  - The nature of laparoscopic surgery makes it likely to benefit from current and
      future developments in virtual reality and telepresence technology. High
      definition screens, three-dimensional sensory feedback and remote dextrous
      manipulation will be the next major developments in laparoscopic surgery.
      Simulators may be used in surgical training and in the evaluation of surgical
      capability.

PMID- 7827925
TI  - Surgical aspects of Behcet's disease.
AB  - Behcet's disease is an uncommon condition that is managed primarily by medical
      therapy. Nevertheless, the widespread manifestations of the disease mean that
      surgeons from many different subspecialties may be involved in the care of
      patients. This is especially so for the treatment of life-threatening
      complications. For this reason the surgeon needs to consider Behcet's disease in
      the differential diagnosis of many conditions and to be aware of the general
      principles underlying the surgical care of affected patients.

PMID- 7827926
TI  - Familial adenomatous polyposis.
AB  - Familial adenomatous polyposis (FAP) is an autosomal dominant condition resulting
      in the development of more than 100 adenomatous polyps in the large bowel. In
      addition, a number of extracolonic manifestations of the condition may occur.
      Recently, increasing knowledge relating to the extracolonic abnormalities, and
      localization and sequencing of the gene for FAP, have had important implications
      for screening and long-term follow-up of those affected. In this review the
      natural history of the disease and the extracolonic manifestations associated
      with it are considered. Surgical management and advances in understanding at a
      molecular level are discussed, as well as the problems relating to screening for
      FAP and the implications of the new knowledge.

PMID- 7827927
TI  - Systemic responses in patients with intermittent claudication after treadmill
      exercise.
AB  - The effect of 5 min treadmill exercise was investigated in claudicant patients
      and healthy controls; systemic neutrophil count, plasma thromboxane and von
      Willebrand's factor (a marker for endothelial injury) were measured. Median
      (interquartile range (i.q.r.)) resting neutrophil count was 5.6 (5.2-6.0) x 10(6)
      cells l-1 in claudicants and 2.8 (2.6-3.2) x 10(6) l-1 in controls (P < 0.05);
      this increased in those with claudication to 7.1 (6.2-7.7) x 10(6) l-1
      immediately after exercise (P < 0.05). The resting plasma thromboxane level was
      32.1 (25.0-60.0) pg ml-1 in claudicants and rose to 135.0 (104.0-141.3) pg ml-1
      15 min after exercise, compared with a rise from 25.0 (22.0-33.5) to 55.5 (33.0
      67.0) pg ml-1 in controls (P < 0.05). The resting serum von Willebrand's factor
      level was 127 (110-135) units dl-1 in claudicants compared with 60 (48-71) units
      dl-1 in controls; this difference persisted after exercise (P < 0.01). In
      patients with claudication, the level of von Willebrand's factor increased to 150
      (140-156) units dl-1 60 min after exercise (P < 0.05). Free radical scavenging
      capacity was also investigated by measuring the plasma antioxidant activity of
      glutathione peroxidase and its essential non-metal cofactor selenium. Scavenging
      capacity was lower in claudicant patients whose median (i.q.r.) glutathione
      peroxidase activity (change in absorbance per min per ml plasma) was 2.84 (2.39
      3.61) versus 3.24 (3.06-3.79) in controls (P < 0.05). Similarly, plasma
      concentrations of selenium were lower in claudicants at a median (i.q.r.) of 75.0
      (58.0-81.0) micrograms l-1 compared with 88.0 (75.0-92.5) micrograms l-1 in
      controls (P < 0.05). Exercise in claudicant patients leads to neutrophilia and
      thromboxane production with subsequent endothelial injury. The antioxidant
      activity of glutathione peroxidase is reduced in patients with claudication and
      may allow the unopposed action of free radicals to damage endothelium.

PMID- 7827928
TI  - Economic evaluation of standard heparin and enoxaparin for prophylaxis against
      deep vein thrombosis in elective hip surgery.
AB  - Deep vein thrombosis (DVT) is a common complication in patients undergoing
      elective hip surgery. Because of the associated risk of pulmonary embolism,
      prophylaxis with standard (unfractionated) heparin is becoming increasingly
      important. Recent clinical trials have shown a low molecular weight form of
      heparin, enoxaparin, to be more effective than standard heparin in preventing
      DVT, but the new drug is also more expensive. Data on clinical effectiveness and
      cost were combined in an economic evaluation of the two regimens. It was found
      that prophylaxis with enoxaparin would be expected to lead to a net saving of 20
      pounds per patient. The economic results are sensitive to the costs of
      enoxaparin, the costs of drug administration and the probability of false
      clinical diagnosis of DVT or pulmonary embolism.

PMID- 7827929
TI  - Effect of ranitidine on soluble interleukin 2 receptors and CD8 molecules in
      surgical patients.
AB  - The effect of perioperative immunomodulation with the H2-receptor antagonist
      ranitidine on postoperative changes in soluble interleukin (IL) 2 receptor and
      soluble CD8 levels was assessed in 24 patients undergoing major elective
      abdominal surgery. Eleven patients were randomized to receive intravenous
      ranitidine 100 mg twice daily for 4 days from skin incision, followed by oral
      ranitidine 150 mg twice daily for a further 5 days; 13 control patients received
      no ranitidine. Routine blood analysis, clinical data, duration of surgery,
      anaesthesia, antibiotic prophylaxis and perioperative blood transfusion were
      similar in the two groups. Serum concentrations of soluble IL-2 receptor and CD8
      were measured before operation (day 0) and in the morning of postoperative days
      1, 3 and 9 using commercial enzyme-linked immunosorbent assay kits. In patients
      treated with ranitidine, the serum level of soluble IL-2 receptor increased from
      day 0 to day 9 (P < 0.01); in control patients it decreased from day 0 to day 1,
      did not change significantly by day 3 and increased by day 9. The change from day
      0 to day 1 was significantly different between the two groups (P < 0.01). Five of
      the 13 control patients developed postoperative infectious complications. No
      significant differences were shown in soluble CD8 concentration during the
      postoperative period. The postoperative change in soluble IL-2 receptor level may
      reflect lymphocyte activation status; ranitidine appears to promote activation of
      mainly CD4-positive lymphocytes since serum levels of CD8 were unchanged.
      Ranitidine may, therefore, improve immune function during major surgery.

PMID- 7827930
TI  - Multi-agent therapy in the treatment of sepsis-induced microvascular injury.
AB  - Cyclo-oxygenase inhibition (with ibuprofen) combined with histamine (H1, H2)
      receptor antagonism (with diphenhydramine and cimetidine) attenuates
      microvascular leak injury in sepsis syndromes. Ibuprofen reduces microvascular
      injury by limiting oxygen radical production by neutrophils. Histamine is known
      to inhibit this oxygen radical production, an effect antagonized by cimetidine.
      In the present study neutrophils isolated from pigs made septic with Pseudomonas
      organisms exhibited a significant (P < 0.05) increase in the production of the
      oxygen radicals, superoxide anion (O2-, 133 per cent) and hypochlorous acid
      (HOCl, 38 per cent). Ibuprofen used alone attenuated this sepsis-stimulated
      overproduction. Addition of the antihistamines cimetidine and diphenhydramine
      produced a significant increase in oxygen radical production (P < 0.05), by 122
      per cent (O2-) and 47 per cent (HOCl), equivalent to that in untreated septic
      animals. This coincided with a significant deterioration in pulmonary compliance
      (P < 0.05) compared with that found in control animals and those treated with
      ibuprofen alone, and a significant accumulation of extravascular lung water (P <
      0.05) at 240 and 300 min versus baseline. Histamine receptor antagonism may
      inadvertently enhance microvascular injury in sepsis.

PMID- 7827931
TI  - Parathyroid function following ligation of the inferior thyroid arteries during
      bilateral subtotal thyroidectomy.
AB  - A randomized controlled trial was performed to compare two techniques of
      bilateral subtotal thyroidectomy for non-toxic nodular goitre with regard to
      postoperative parathyroid function. The 50 patients in group 1 underwent ligation
      of the trunks of the inferior thyroid arteries. In group 2 (50 patients) the
      branches of these arteries were suture-ligated at the thyroid capsule. Total
      calcium, ionized calcium and parathyroid hormone levels were determined before
      operation, and 6, 24 and 72 h after surgery. Ninety-one patients were seen at
      follow-up 5-10 months after operation. Ten patients in group 1 and 12 in group 2
      required calcium and/or vitamin D supplementation for symptomatic hypocalcaemia
      in the immediate postoperative period. At follow-up only one patient in each
      group had mild hypoparathyroidism. No statistically significant differences were
      found between groups regarding total calcium, ionized calcium and parathyroid
      hormone levels. Truncal ligation of the inferior thyroid arteries during
      bilateral subtotal thyroidectomy does not cause hypoparathyroidism or
      hypocalcaemia.

PMID- 7827932
TI  - Recovery from bilateral vocal cord paralysis following thyroid surgery.

PMID- 7827933
TI  - Early results of laparoscopic intraperitoneal onlay mesh repair for inguinal
      hernia.
AB  - Over a 15-month period, 39 patients (37 men) of mean age 52 years underwent
      laparoscopic inguinal hernia repair. Seven patients had bilateral hernia. Forty
      six hernias (33 indirect, five direct, eight both direct and indirect) were
      repaired. A piece of polypropylene mesh measuring 8 x 10 cm was used to cover the
      direct and indirect spaces with an endoscopic multifeed hernia stapler. The mean
      operating time for unilateral and bilateral repair was 49 and 63 min respectively
      (range 25-90 min). One-third of patients required no postoperative analgesia and
      only seven had more than one injection of pethidine. The median postoperative
      stay was 1 (range 1-3) days. The mean period to resumption of daily activities
      was 7 (range 4-21) days. Three patients complained of paraesthesia of the lateral
      aspect of the thigh and one developed a hydrocele. Two recurrences were noted on
      follow-up at 3 months.

PMID- 7827934
TI  - Proliferating cell nuclear antigen in the assessment of Barrett's mucosa.
AB  - Proliferating cell nuclear antigen (PCNA) expression was assessed in oesophageal
      epithelium from 70 patients with Barrett's oesophagus. PCNA counts were expressed
      in the form of a PCNA index. There were 24 patients with dysplastic epithelium,
      nine with regenerative atypia, 18 with benign histology and 19 with
      adenocarcinoma arising in Barrett's epithelium. The PCNA index of malignant
      tissue was significantly different from that of benign (P < 0.001) and dysplastic
      (P < 0.05) specimens. PCNA indices in histologically normal Barrett's epithelium
      adjacent to a tumour were significantly different (P < 0.001) from those in
      normal Barrett's epithelium with no adjacent tumour. These findings support the
      use of PCNA measurement in the assessment of Barrett's epithelium.

PMID- 7827935
TI  - Gamma probe-guided sentinel node biopsy to select patients with melanoma for
      lymphadenectomy.
AB  - A novel approach is described by which to identify the sentinel lymph node in
      patients with stage I melanoma. The technique involves a combination of
      intradermal patent blue V injection and gamma probe-assisted surgery. Eleven
      patients with previously resected cutaneous melanoma, clinical stage I (Breslow
      thickness 1.35-3.20 mm), underwent sentinel node biopsy. Before surgery
      lymphoscintigraphy was performed to evaluate the pathways of lymphatic drainage
      from the site of the previously resected melanoma. A handheld gamma probe was
      used to localize the sentinel node and to define the exact site of incision. At
      the same time, patent blue V (0.1-0.2 ml) was injected intracutaneously on either
      side of the scar to visualize the afferent lymphatic ducts and lymph nodes. By
      combining the use of the gamma probe and vital dye staining, the sentinel node
      could easily be localized and identified in all 11 patients. After removal of the
      sentinel node(s) no residual radioactivity could be traced. In four patients with
      micrometastases in the sentinel node standard lymph node dissection was
      performed, including excision of the biopsy site; in only one lymphadenectomy
      specimen were micrometastases found in two other lymph nodes.

PMID- 7827936
TI  - Groin dissection in malignant melanoma.
AB  - A total of 205 patients who underwent groin dissection for malignant melanoma
      were reviewed to document complications and survival rates. Wound complications
      included skin-edge necrosis in 8 per cent, wound infection in 16 per cent,
      lymphocele in 5 per cent and lymphorrhoea in 11 per cent. Lymphoedema of the
      operated leg below the knee was noted in 40 per cent, but all patients had
      localized oedema of the anteromedial thigh. The 5-year overall and disease-free
      survival rates were 43 and 35 per cent respectively when only the inguinal nodes
      were involved; they were 34 and 21 per cent with involvement of both the inguinal
      and deep nodes. The 10-year survival rate for these two groups was 39 and 25 per
      cent respectively, which suggests that a thorough, complete dissection of the
      deep nodes is worth-while when the inguinal nodes are palpably positive.

PMID- 7827937
TI  - Enhanced Kupffer cell activity after repeated hepatic arterial ischaemia in an
      experimental model.
AB  - Kupffer cells are important for host defence against both foreign invaders and
      neoplasia. Several studies have demonstrated that ischaemia and reperfusion
      activates Kupffer cells. The effect of hepatic arterial ischaemia on Kupffer cell
      function was assessed using blood clearance and organ uptake of radiolabelled
      Escherichia coli. Transient ischaemia for 1 h did not alter Kupffer cell function
      in comparison with sham operation. However, prolonging arterial ischaemia for 2 h
      stimulated Kupffer cell function; both the phagocytic index and liver uptake of
      radiolabelled E. coli increased significantly (P < 0.01). Furthermore, this
      enhanced Kupffer cell activity was achieved each time the ischaemia was induced
      over a period of 5 days compared with repeated sham procedures (P < 0.05). Serum
      tumour necrosis factor (TNF) was significantly released after both single and
      repeated arterial occlusion for 2 h (P < 0.01). These observations show that
      transient arterial ischaemia enhances Kupffer cell function and induces TNF
      production.

PMID- 7827938
TI  - Effect of platelet-activating factor on cold-preserved liver grafts.
AB  - Platelet-activating factor (PAF) may play an important role in graft injury in
      liver transplantation. Livers excised from male Wistar rats were preserved in
      University of Wisconsin solution for 6 h and then perfused with Krebs-Henseleit
      solution containing vehicle (bovine serum albumin) or PAF. Impairment of
      parenchymal cells was assessed by reference to tissue adenosine triphosphate
      levels, oxygen consumption and alanine aminotransferase activity in the effluent.
      The effect on non-parenchymal cells was evaluated by measurement of purine
      nucleoside phosphorylase and alanine aminotransferase levels in the effluent.
      Administration of as little as 1.0 ng kg-1 PAF caused a significant decrease in
      adenosine 5'-triphosphate concentration and oxygen consumption (P < 0.05),
      although non-parenchymal cell injury was not affected. PAF can therefore cause
      liver graft dysfunction with hepatocytes as the main target, even in the absence
      of microcirculatory disturbance secondary to interaction between blood cells and
      endothelial cells.

PMID- 7827939
TI  - Amelioration of experimental acute pancreatitis with a potent platelet-activating
      factor antagonist.
AB  - The effect of a potent platelet-activating factor (PAF) antagonist, BB-882, on an
      experimental model of acute pancreatitis induced in male Wistar rats by a
      technique of microvascular ischaemia was studied. A single intraperitoneal
      injection of BB-882 (5 mg/kg) 30 min after induction of the disease in 12 animals
      significantly reduced (P < 0.001) the rise in the level of serum amylase (mean
      2477 (range 2100-3280) units/l) compared with that in 12 control animals (mean
      3928 (range 2800-5900) units/l) and significantly improved (P < 0.001) the mean
      pancreatic histology score (5.0 (range 3-10) versus 12.3 (range 8-18) in
      controls). PAF is a biologically active ether phosphorylcholine synthesized in
      cell membranes and a potent inflammatory mediator. Pancreatic tissue levels of
      this compound are increased in experimental acute pancreatitis and pretreatment
      with PAF receptor antagonists can ameliorate the progression of this disease. BB
      882 alters the early course of experimental pancreatitis and may have a clinical
      therapeutic role.

PMID- 7827940
TI  - Risk factors for bile duct injury in laparoscopic cholecystectomy: analysis of 49
      cases.
AB  - Forty-nine bile duct injuries, representing 0.8 per cent of 6076 laparoscopic
      cholecystectomies performed in the Netherlands in 1990-1992, were reviewed. The
      aim of the study was to classify the injuries according to severity, to identify
      possible risk factors contributing to the aetiology of such injuries and to
      correlate these with the severity of the injury. On the basis of operative
      findings, bile duct injuries were classified from minor (classes I-IIIa) to
      extensive with loss of bile duct tissue (IIIb) or localization in the liver hilum
      (IV). Of 49 injuries, there were 11 in class I, six in class II, ten in class
      IIIa, 18 in class IIIb and four in class IV. In 16 patients the injury was
      detected during laparoscopic cholecystectomy and the procedure converted to
      laparotomy. The duct injury was minor (class I-IIIa) in 14 of these 16 patients.
      In 20 of the 33 patients in whom identification of the injury was delayed to a
      second or third operation, more severe types of injury (classes IIIb and IV) were
      observed. Delayed detection was associated with greater severity (P = 0.002). Of
      eight patients with histologically proven acute cholecystitis at cholecystectomy,
      seven suffered severe injury (class IIIb or IV). Surgical experience with
      laparoscopic cholecystectomy was an important factor in the incidence of bile
      duct injury.

PMID- 7827941
TI  - Laparoscopic management of cholecystocolic fistula.

PMID- 7827942
TI  - Circular staplers versus the biofragmentable ring for colorectal anastomosis: a
      prospective randomized study.

PMID- 7827943
TI  - Wheat fibre, lactulose and rectal mucosal proliferation in individuals with a
      family history of colorectal cancer.
AB  - In a single-blind study 38 individuals at increased risk of developing colorectal
      cancer because of a family history of the disease were randomized to take 10.5 g
      wheat fibre (Trifyba) or 60 ml lactulose daily for 12 weeks. Rectal biopsies were
      taken before and after treatment and rectal mucosal proliferation was measured by
      the crypt cell production rate (CCPR). The mean(s.d.) CCPR was significantly
      lower in those taking wheat fibre after 12 weeks (7.2(3.4) crypt cells per crypt
      per h) compared both with values obtained before treatment with wheat fibre
      (10.2(5.1) crypt cells per crypt per h; P = 0.02) and after treatment with
      lactulose (9.4(3.8) crypt cells per crypt per h; P = 0.05). Proliferation in the
      lactulose group was not significantly different at 12 weeks compared with the
      value obtained before treatment. This study confirms an antiproliferative effect
      of wheat fibre in a group of high-risk individuals.

PMID- 7827944
TI  - Sigmoidoscopy with a view.

PMID- 7827945
TI  - Bacterial translocation during peroperative colonic lavage of the obstructed rat
      colon.
AB  - Peroperative antegrade colonic lavage is often performed before primary
      anastomosis in emergency colonic surgery. The influence of colonic lavage on
      bacterial translocation from the obstructed colon was determined. Forty female
      Wistar rats were studied in four groups: (1) control; (2) non-obstructed with
      lavage; (3) obstructed; and (4) obstructed with lavage. Ligature obstruction of
      the rectum was performed in groups 3 and 4. Some 4 days later 35S-radiolabelled
      Escherichia coli was inoculated into the colon of all animals. Groups 2 and 4
      underwent colonic lavage. Lavage in the group 4 animals with left-sided colonic
      obstruction significantly increased the levels of E. coli in regional nodes,
      liver, spleen, lung, kidney and blood (as assessed by organ culture and
      scintillation counting) compared with those in groups 1, 2 and 3 (P < 0.05).
      These results suggest that peroperative lavage of the obstructed colon
      significantly increases the level of bacterial translocation.

PMID- 7827946
TI  - Use of Marlex mesh in the repair of recurrent incisional hernia.

PMID- 7827947
TI  - Fatal intestinal ischaemia following laparoscopic cholecystectomy.

PMID- 7827948
TI  - Administration of heparin and antibiotic prophylaxis.

PMID- 7827949
TI  - Reversal of jejunoileal bypass in patients with morbid obesity.

PMID- 7827950
TI  - Breast-conserving surgery and tumour bed positivity in patients with breast
      cancer.

PMID- 7827951
TI  - Transient femoral nerve palsy complicating preoperative ilioinguinal nerve
      blockade for inguinal herniorrhaphy.

PMID- 7827952
TI  - Practical score to aid decision making in doubtful cases of appendicitis.

PMID- 7827953
TI  - Inappropriate neutrophil activation in venous disease.

PMID- 7827954
TI  - Management of bile duct stones in the era of laparoscopic cholecystectomy.

PMID- 7827955
TI  - Nature and the multiple functions of the 67-kD elastin-/laminin binding protein.
AB  - Numerous cell types, including fibroblasts, vascular smooth muscle cells,
      chondroblasts, monocytes, neutrophils, and several tumor cells express the 67-kD
      galactolectin, homologous to the alternatively spliced variant of beta
      galactosidase. The 67-kD protein resides on the cell surfaces and is capable of
      interacting with elastin, laminin and collagen type IV. This peripheral membrane
      protein binds its matrix ligands but only in the absence of galactosugars,
      whereas binding of galactosugar-containing moieties to its lectin site changes
      its molecular folding which causes discharge of the ligand and release of the
      receptor from the cell surface. This review will address the functional
      significance of the single receptor that interacts with multiple matrix proteins
      and can be shed from cell surfaces by galactosugars. I will emphasize the role of
      the 67-kD protein in divergent cellular processes, such as cell-matrix
      attachment, matrix assembly, cellular chemotaxis, and active migration through
      the vascular walls.

PMID- 7827956
TI  - Cell localization and redistribution of the 67 kD laminin receptor and alpha 6
      beta 1 integrin subunits in response to laminin stimulation: an immunogold
      electron microscopy study.
AB  - The 67 kDa laminin receptor (67LR), one of several cell surface laminin-binding
      proteins, is involved in the interactions between cancer cells and laminin during
      tumor invasion and metastasis. A 37 kDa polypeptide (37LRP), previously
      identified as the 67LR precursor, is abundantly present in the cytoplasm and has
      been implicated in polysome formation. To better understand the cellular
      localization of the 67LR and its precursor, transmission electron microscopic
      studies of human melanoma A2058 cells were carried out using immunogold labeling
      and a variety of antibodies: (a) affinity purified antibodies directed against
      37LRP cDNA-derived synthetic peptides; (b) anti-67LR monoclonal antibodies raised
      against intact human small cell lung carcinoma cells; and (c) monoclonal
      antibodies against the subunits of the integrin laminin receptor, alpha 6 beta 1.
      Double-labeling immunocyto-chemistry revealed that anti-67LR monoclonal
      antibodies as well as anti-37 LRP antibodies recognized antigens that were
      localized in the cytoplasm in electron dense structures. As expected, cell
      membrane labeling was also observed. Surprisingly, alpha 6 and beta 1 integrin
      subunits were detected in the same cytoplasmic structures positive for the 67LR
      and the 37LRP. After addition of soluble laminin to A2058 cells in suspension,
      the number of labeled cytoplasmic structures increased especially in the vicinity
      of the plasma membrane, and were exported onto the cell surface. Neither
      fibronectin nor BSA induced such an effect. The data demonstrate that the 67 LR
      and the 37 LRP antibodies detect colocalized antigens that are in cytoplasmic
      structures with alpha 6 beta 1 integrin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7827957
TI  - Role of ICAM-3 in intercellular adhesion and activation of T lymphocytes.

PMID- 7827958
TI  - Cytokines and cell adhesion molecules in tumor-endothelial cell interaction and
      metastasis.

PMID- 7827959
TI  - Depressed immune surveillance against cancer: role of deficient T cell:
      extracellular matrix interactions.
AB  - Although T cells infiltrate malignant tumors, the local immune response is
      usually inefficient and tumors escape destruction. While extracellular matrix
      proteins strongly costimulate T cell responses in normal individuals, our studies
      indicate that peripheral blood T cells from cancer patients and tumor
      infiltrating cells respond poorly or are resistant to stimulative signals
      mediated by collagen I and IV and fibronectin. Moreover, the adhesive properties
      of cancer T cells are markedly depressed. Those functional deficiencies are
      paralleled by variable deficits in integrin and non-integrin T cell receptors for
      extracellular matrix. Immunotherapy with BCG causes a dramatic but transient
      increase in T cell: ECM interactions.

PMID- 7827960
TI  - The therapeutic potential of targeting adhesion molecules in rheumatoid
      arthritis.

PMID- 7827961
TI  - Fibronectin and lymphocytes in inflammatory tissue. Studies of blood and synovial
      fluid lymphocytes from patients with rheumatoid arthritis and other inflammatory
      arthritides.
AB  - Lymphocytes infiltrating tissues under chronic inflammatory conditions are often
      surrounded by deposits of fibronectin. We have studied the possibility that this
      reflects capacity of lymphocytes to synthesize fibronectin and compared
      lymphocytes from blood and synovial fluid with respect to fibronectin
      interactions. In vitro activated blood lymphocytes exhibited synthesis of a
      fibronectin-like molecule. Synovial fluid cells appeared to synthesize the same
      high molecular weight component spontaneously. Activated blood lymphocytes have
      cell surface fibronectin and surface components of lower molecular weight which
      could be immunoprecipitated with anti-fibronectin antibodies as well as by
      insolubilized collagen. Synovial fluid cells showed cell surface fibronectin as
      revealed by immunocytochemical detection but seemed to lack or have relatively
      small amounts of the low-molecular weight fibronectin-like surface components.
      Synovial fluid T cells from arthritis patients showed adhesion to fibronectin.
      Immunocytochemistry demonstrated presence of alpha 4 and alpha 5 beta 1 integrins
      at the surface of the synovial fluid T cells and RGD and LDV peptides inhibited
      adhesion of the cells to fibronectin. Noteworthy, a portion of synovial fluid
      cells with lymphocyte markers also bound to plastic. Blood lymphocytes from the
      same arthritis patients displayed relatively poor or negligible adhesion to
      fibronectin unless activated to blast transformation and did not attach to
      plastic. Taken together these results suggest that activated lymphocytes from
      blood and synovial fluid may use fibronectin of exogenous or endogenous origin
      when interacting with tissues during inflammatory processes. Furthermore, the
      presence at the lymphocyte surface of components of different molecular weight
      precipitated by anti-fibronectin antibodies suggests that fibronectin or its
      fragments can bind to the lymphocyte surface.

PMID- 7827962
TI  - The role of cellular and extracellular matrix adhesion proteins in organ
      transplantation.
AB  - The specific adhesion of cells to other cells or to particular tissue
      microenvironments is a basic function of cell migration and recognition, and
      underlines many biologic processes including embryogenesis, repair and immunity.
      Leukocytes express an array of surface receptors broadly known as "accessory
      adhesion molecules." which mediate most cell-cell interactions, direct lymphocyte
      traffic between anatomical compartments, and facilitate cellular adhesion to the
      inflammation or alloantigenic sites (Springer 1990). In addition, adhesion
      molecules are involved in the process of antigen recognition, and may costimulate
      cell activation and transformation. These proteins are thought to affect the very
      early antigen independent events between host leukocytes and vascular
      endothelium. Because of these activities, the subject of adhesion molecules is
      gaining interest in the field of organ transplantation, in both conceptualization
      and development of novel therapeutic strategies (de Sousa et al. 1991, Kupiec
      Weglinski et al. 1993a, Heemann et al. 1993).

PMID- 7827963
TI  - Adhesion molecule deficiencies and their clinical significance.
AB  - Adhesion molecules play a major role in the recruitment of neutrophils to the
      site of inflammation. Currently, two congenital hereditary Leukocyte Adhesion
      Deficiency (LAD) syndromes are recognized. LAD I is due to the absence of the
      beta subunit of the integrin molecule, while LAD II is caused by a deficiency of
      Sialy1 Lewis X, the neutrophil ligand for selectins. Clinically, both syndromes
      are characterized by recurrent bacterial infections, more severe in LAD I.
      Developmental abnormalities (growth and mental retardation) constitute a
      prominent feature of LAD II and may be attributed to a general defect found in
      fucose metabolism in LAD II. Neutrophil motility was found to be defective in
      both syndromes. Using activated umbilical endothelial cells, we showed that LAD I
      neutrophil do not bind to cells expressing ICAM-1, while LAD II cells do not bind
      to endothelial cells expressing E- or P-selectin. Skin window technique showed a
      marked decrease in margination in both syndromes. Using intravital microscopy we
      were able to show that the basic defect in LAD II is in the "rolling" phase,
      while in LAD I, firm adhesion and transmigration are defective. Studies of these
      two rare conditions emphasized the important in vivo roles of adhesion molecules
      in host defense mechanism.

PMID- 7827964
TI  - Functional interactions of fibronectin and TNF alpha: a paradigm of physiological
      linkage between cytokines and extracellular matrix moieties.

PMID- 7827965
TI  - Molecular tools for the analysis of cell adhesion.

PMID- 7827966
TI  - One-dimensional double-quantum magic-angle-spinning NMR of deuterated solids.
AB  - An approach to double-quantum magic-angle spinning (2Q-MAS) of spin I = 1 with a
      time-share irradiation, resulting in a one-dimensional (1D) MQ spectrum, is
      demonstrated in this paper. The experiment was carried out with perdeuterated
      dimethoxybenzene and showed that the 2Q transitions were insensitive to the
      spinning axis deviation from the magic angle. The 1D-2Q-MAS scheme may also be
      applied to nitrogen-containing solids.

PMID- 7827967
TI  - High-resolution 1H NMR in solids with frequency-switched multiple-pulse
      sequences.
AB  - A new pulse sequence for abundant-spin NMR in solids, called FSLG240W, is
      demonstrated. The sequence employs phase-coherent frequency-switching of the rf
      irradiation to induce opposite rotations around the magic-angle axis in the
      rotating frame. Three 4 pi/3 rotations in one sense are followed by three 4 pi/3
      rotations in the opposite sense. Observation windows separate each rotation. The
      pulse sequence cancels out the average dipolar Hamiltonian, the first-order
      correction terms, and the most deliterious second-order terms. The pulse sequence
      has a short cycle time and a high scaling factor kappa = 1/square root of 3, but
      is sensitive to rf inhomogeneity. We demonstrate slightly better resolution than
      either MREV8 or BR24 on a small spherical sample of L-alanine.

PMID- 7827968
TI  - Determination of spin-5/2 quadrupolar coupling with two-pulse sequences.
AB  - The density matrix of a spin-5/2 system excited by two in-phase pulses separated
      by a delay tau 2 is calculated from the equilibrium state to the end of the
      second pulse. The interaction involved throughout the computation is the first
      order quadrupolar interaction. Consequently, the results are valid for any ratio
      of the quadrupolar coupling to the amplitude of the radio-frequency pulse. It is
      shown that single- and multi-quantum coherences developed during the first pulse
      are detected at the end of the second pulse through single-quantum coherences.
      Other two-pulse sequences with various phase cyclings as well as the rotary echo
      sequence are also discussed and illustrated with the nuclei 27Al in a single
      crystal of corundum Al2O3.

PMID- 7827969
TI  - The bond angle dependence of the asymmetry parameter of the oxygen-17 electric
      field gradient tensor.
AB  - From primarily geometric starting points, simple formulae for the bond angle
      dependence of the 17O quadrupolar asymmetry parameter eta were derived.
      Expressions for the bond angle dependence of the components of the electric field
      gradient (EFG) were first derived by Vega. Poplett used these expressions to
      discuss the 17O NQR results obtained for the water molecule. The formulae
      presented in this paper were derived essentially from other starting points and
      contain only the bond angle of a A- 17O-A oxygen bridge and all details
      concerning the electron distribution within the bonds will cancel out. Since no
      assumptions concerning the p-orbital occupancies had to be invoked, these
      geometric eta formulae are valid for most bridging oxygens. A necessary
      prerequisite of the eta formulae was that the electron distribution around the
      oxygen atom under study should exhibit C2v or D2 symmetry. The formulae were
      applied to explain the data of water molecules in the gaseous state, of various
      ice polymorphs and of crystal water. As supposed, the theory worked best for the
      free water molecule because of its perfect C2v symmetry. The differences between
      experiment and theory for water in solid compounds were mostly smaller than 6%.
      In the case of silicates and zeolites it was demonstrated that the eta formulae
      correctly described the experimental trends of the 17O NMR measurements of these
      substances. It could be demonstrated that reliable A-O-A-bond angles could be
      obtained from an eta measurement independent of the bond partner A. Comparing
      calculated eta values with ab initio calculations of this parameter, the largest
      difference was observed in the case of a Si-O-Si bond angle near 90 degrees. The
      eta formulae gave slightly lower eta values than ab initio calculations but the
      general trends were correctly reflected.

PMID- 7827970
TI  - High-field 13C solid-state NMR studies of stream humic and fulvic acids with fast
      magic-angle spinning.
AB  - Standard samples of stream humic and fulvic acids have been studied by high
      resolution 13C solid-state NMR. The spectra have been recorded at a high (9.4 T)
      magnetic field using 1H-13C cross-polarization (CP) and proton high-power
      decoupling (HPDEC) with fast (up to 15 kHz) magic-angle spinning (MAS). The
      widths of the spectral lines decrease with increasing spinning rate. This is
      probably due to the overlap of spinning sidebands with resonances at low speeds
      and to a more effective averaging of anisotropic broadening at high speeds.
      However, fast MAS modulates the CP signal intensities, making quantitative
      analysis very difficult.

PMID- 7827971
TI  - Molecular dynamics of the methylammonium cation in [CH3NH3]5Bi2Cl11.
AB  - The 1H relaxation times T1 of methylammonium in chlorobismuthate(III) were
      measured in the temperature range from 50 to 270 K with a SXP 4/100 Bruker pulse
      spectrometer at 55.2 MHz. It was found that the T1 temperature dependence has
      three minima. The individual relaxation rates of the three-proton groups can be
      described by the O'Reilly and Tsang formula. The results obtained from the
      fitting procedure, using the typical Woessner formula for complex compounds,
      allow to conclude that the low-temperature minimum is due to the relaxation of
      all CH3 groups and the other two minima are due to the relaxation of two and four
      NH3 groups, respectively. This assignment is based on the X-ray results showing
      that methylammonium cations are differently bonded in this crystal.

PMID- 7827972
TI  - Magnetic field-induced orientation of crystallites in powdered samples of layered
      compounds: explanation and application.
AB  - Magnetic field-induced orientation phenomena observed in many solid state NMR
      experiments of layered compounds have been explained in terms of the magnetic
      properties of these materials. Utilization of the effect to obtain "single
      crystal" spectra of powder samples leads to sensitive measurements of the NMR
      parameters which are otherwise not possible.

PMID- 7827973
TI  - Structure of hydrated layers on silicate electrode glasses.
AB  - The structural changes of the silicate framework in hydrated layers of silicate
      electrode glasses compared with untreated glasses as well as the quality and
      quantity of water and its ionic species stored in the layer have been
      investigated by high-resolution solid-state nuclear magnetic resonance (NMR)
      techniques [29Si magic-angle spinning (MAS), 29Si cross-polarization (CP) MAS, 1H
      high-speed MAS, 1H CRAMPS and 1H Echo NMR]. To support the results, infrared (IR)
      spectroscopy, thermal analysis and sodium ion concentration analyses were used.
      It was found that at least two different water species exist in the hydrated
      layer: SiOH groups and not very mobile hydrogen-bonded molecular water.
      Concerning the framework modified, Q3 groups [(SiO)3SiOH] were formed in the
      hydrated glass. During the swelling process a condensation of silanol groups
      formed took place to a great extent.

PMID- 7827974
TI  - 139La nuclear magnetic resonance characterisation of La2O3 and La1-xSrxMO3 where
      M = Cr, Mn or Co.
AB  - 139La Nuclear magnetic resonance (NMR) spectra have been used to obtain nuclear
      quadrupole coupling parameters for La2O3 and a series of perovskites La1-xSrxMO3
      (where M = Cr, Mn or Co). Depending on the doping level of SrO2 these materials
      are either paramagnetic or ferromagnetic at room temperature. Magnetic
      transferred hyperfine effects are strongly in evidence in the Mn compounds. A
      59Co NMR spectrum was observed in LaCoO3. A precision measurement of the nuclear
      quadrupole coupling constant in La2O3 was made by nuclear quadrupole resonance
      (NQR) spectroscopy.

PMID- 7827975
TI  - Non-exponential behavior of the nuclear magnetization in H-doped copper oxides.
AB  - Measurement of the spin lattice relaxation time in H-doped Y2BaCuO5 and YBa2Cu3O6
      has revealed a power law growth of the nuclear magnetization M for short times
      following a saturation pulse sequence. Preliminary experimental results yield
      exponents of 1/2 and 1/3, depending on the amount of hydrogen present in the
      sample. We extend Blumberg's theory for relaxation due to paramagnetic centers
      via dipole-dipole interaction in the absence of spin diffusion to obtain M
      approximately tD/6 where D is the dimensionality of the system. This yields
      exponents of 1/2 and 1/3 for three- and two-dimensional systems, respectively. At
      long times the magnetization growth becomes exponential.

PMID- 7827976
TI  - 23Na magic-angle spinning nuclear magnetic resonance of central and satellite
      transitions in the characterization of the anhydrous, dihydrate, and mixed phases
      of sodium molybdate and tungstate.
AB  - 23Na Magic-angle spinning nuclear magnetic resonance (MAS NMR) spectra of pure
      phases for Na2MoO4, Na2MoO4 x 2H2O, Na2WO4, and Na2WO4 x 2H2O have led to the
      determination of accurate values for the quadrupole coupling parameters and
      isotropic chemical shifts for all Na sites. The analysis of the spectra involves
      a combination of simulations of the line shapes for the central transitions and
      the manifold of spinning sidebands for the satellite transitions. The spectral
      parameters for the pure phases represent a prerequisite for a correct assignment
      and quantitative evaluation of 23Na MAS spectra at different magnetic field
      strengths observed for mixtures of the anhydrous and dihydrate phases. Such phase
      mixtures are observed, for example, for some commercial samples of Na2MoO4 or may
      be generated by (i) exposure of the anhydrous phases to a humid atmosphere or
      (ii) gently heating the dihydrates. The quadrupole coupling parameters for the
      two Na sites in the dihydrates are tentatively assigned to the two
      crystallographically distinct Na atoms in the asymmetric unit by calculations of
      an approximate dependency of the electric field gradient tensor on the local
      geometry for the Na sites.

PMID- 7827977
TI  - Solid-state 27Al and cross-polarization 13C magic-angle spinning nuclear magnetic
      resonance characterisation of aluminas derived from basic aluminum succinate.
AB  - Solid-state 27Al and cross-polarization (CP) 13C magic-angle spinning nuclear
      magnetic resonance (MAS NMR) was used to characterise aluminas obtained by
      calcining basic aluminium succinate at different temperatures. In basic aluminium
      succinate, aluminium is in the tetrahedral coordination only. However, in both X
      ray amorphous and gamma-aluminas aluminium is in the tetrahedral and octahedral
      coordination. The intensity of the aluminium peaks is at a maximum for samples
      calcined at 700 degrees C. 13C CP MAS NMR indicates the bonding of Al with carbon
      of the carboxylate group in basic aluminium succinate. Samples calcined at 400
      870 degrees C do not give 13C spectra.

PMID- 7827978
TI  - Use of 19F nuclear magnetic resonance spectroscopy for probing substitution of Al
      for Ga in cloverite.
AB  - The synthesis of gallophosphate cloverite in the presence of aluminium leads to a
      partial substitution of Ga by Al. 27Al and 19F magic-angle spinning nuclear
      magnetic resonance (MAS NMR) studies on this material confirm this substitution.
      27Al MAS NMR shows a broad line at 30 ppm which can be attributed to
      tetrahedrally coordinated Al in the solid. The 19F MAS NMR results are more
      complex. The spectrum presents five lines between -68 ppm and -95 ppm which can
      be assigned to fluorine in D4Rs with variable composition in Ga and Al. Two other
      lines, at -145.6 ppm and -178.2 ppm, may correspond to impurities and to a
      fluorine atom in a pseudo-sodalite cage environment, respectively.

PMID- 7827979
TI  - Fitting of low-intensity wide-line spectra dominated by chemical shift
      anisotropy.
AB  - How experimental parameters affect the appearance, and consequently the fitting,
      of signals having very wide lines is discussed. As these spectra usually have
      very low intensities, pulse sequences that remove acoustic ringing and other
      experimental artefacts have to be used. These pulse sequences introduce further
      spectral distortions. A FORTRAN 77 program was developed that accounts for these
      effects. The fitting of these broad spectra is demonstrated by application to
      207Pb solid-state nuclear magnetic resonance (NMR) spectra.

PMID- 7827980
TI  - Cross-polarization dynamics and spin diffusion in some aromatic compounds.
AB  - The inversion-recovery cross-polarization (IRCP) magic-angle spinning experiment
      has been applied to study the 13C-1H cross-polarization dynamics of protonated
      aromatic carbons in ferrocene, 5,6-dimethoxyindole (DMI) and some indole
      derivatives. Using the 13C-detected proton spin diffusion (SD) experiment
      recently developed by Zhang et al. [Solid State Nucl. Magn. Reson., 1 (1992)
      313], the slow decaying or incoherent stage of the IRCP experiment is shown to be
      controlled by the spin diffusion process at the directly bound proton. Moreover,
      a simple phenomenological model treating spin diffusion as a relaxation process
      provides an excellent agreement with both the IRCP and SD experimental data for
      all the different C-H pairs of DMI and its derivatives. The resulting time
      constants of the non-exponential spin diffusion decays are related to the local
      intra- and intermolecular network of dipolar interactions. This model is
      nevertheless found to be inadequate for ferrocene because intramolecular spin
      diffusion then has an inhomogeneous character.

PMID- 7827981
TI  - Solid Me3Sn(O2CH): molecular and spin dynamics as viewed by 1H, 13C and 119Sn
      nuclear magnetic resonance spectroscopy.
AB  - Because of favourable dynamic properties in the solid state, crystalline
      trimethyltin formate, Me3Sn(O2CH), 1, offers quite unique possibilities to probe
      questions related to molecular dynamics (2 pi/3 Me3Sn reorientation) and to
      structural aspects (rigidity of the polymeric backbone, effectively isolated 1H
      13C spin pair in the bidentate chain-building formate anion) by 1H, 13C and 119Sn
      high-resolution solid-state nuclear magnetic resonance (NMR) methods. The
      combined use of various one- (1D) and two-dimensional (2D) variable-temperature
      NMR experiments, including consideration of the short-time-cross-polarization
      (CP) behaviour of the 1H-13C spin pair in 13C-labelled Me3Sn(O2*CH), 1*, yields a
      fairly comprehensive description of the solid-state structure of 1, also in the
      absence of the single-crystal X-ray structure determination of 1. Taking
      advantage of the anisotropic polarization transfer within the formate 1H-13C spin
      pair allows to relate the orientation of the 1H-13C dipolar interaction, i.e. the
      C-H bond direction to the principal axes system of the 13C shielding tensor of
      the formate 13C from static 13C powder patterns of 1*.

PMID- 7827982
TI  - 1H and 129Xe nuclear magnetic resonance studies of hydrogen chemisorption on
      supported platinum. Application to the metal dispersion and spillover.
AB  - Chemisorption of hydrogen, electron microscopy and 1H nuclear magnetic resonance
      (NMR) have confirmed that the chemical shift of hydrogen chemisorbed on platinum
      is directly related to the size of the metal particles. The influence of the
      hydrogen adsorbate concentration and the chemisorption temperature on the
      chemical shift delta H and the distribution of the hydrogen chemisorbed on these
      particles have been determined. This study also shows how the dispersion can be
      deduced from the variation of delta H with the H2 concentration and clarifies the
      effect of temperature on the concentration of spillover H2. 129Xe NMR of adsorbed
      xenon used as a probe confirmed most of the previous results.

PMID- 7827983
TI  - Retrieval of solid-state 31P nuclear magnetic resonance (NMR) chemical shielding
      parameters: proposal of an approach concerning variable-temperature 31P NMR mass
      spectra of urea phosphate and comparison of different methods.
AB  - Several methods are used to retrieve the principal components of the 31P chemical
      shielding tensor from variable-temperature 31P NMR spectra of urea phosphate
      (both static and spinning at the magic angle at low speeds). A complementary
      approach is proposed for the study of small changes in these parameters, based on
      the measurement of selected side-band intensities which are most sensitive to
      changes in sigma.

PMID- 7827984
TI  - Aluminum to oxygen cross-polarization in alpha-Al2O3 (corundum).
AB  - Experimental results concerning the cross-polarization of two quadrupolar, I =
      5/2 nuclei are presented. It is shown in particular that 27Al spins in alpha
      Al2O3 (corundum) can be spin-locked, and magnetization transferred to the 17O
      spin system. Cross-polarization between pairs of quadrupolar nuclei can cause
      considerable signal-to-noise ratio gains over conventional one- (or two-) pulse
      excitation and should be of use in investigating a number of inorganic solids.

PMID- 7827985
TI  - 27Al-->1H cross-polarization in aluminosilicates.
AB  - Solid-state nuclear magnetic resonance (NMR) cross-polarization (CP) from 27Al to
      1H was set on kaolinite, verified by a variable-contact time experiment and
      applied to ultrastable zeolite Y. The technique is useful for the selective NMR
      observation of AlOH sites in aluminosilicates, especially those from
      extraframework species in zeolites.

PMID- 7827986
TI  - Multiple subtypes of voltage-gated calcium currents in the Edinger-Westphal
      nucleus.
AB  - Avian Edinger-Westphal (EW) neurons provide a unique opportunity to compare
      electrophysiologically the membranes of cell bodies and terminals in the same
      population of neurons. Axons that originate from neurons in the lateral region of
      the EW nucleus form a morphologically distinct presynaptic terminal, known as a
      calyx, on ciliary ganglion neurons. Several studies have shown that calyciform
      terminals in the ciliary ganglion exhibit predominantly N-type, high-voltage
      activated (HVA) calcium channels. The goal of this study was to characterize and
      compare the calcium currents expressed in EW cell somas with those reported in
      the terminals. Whole-cell patch-clamp techniques were used to record from cell
      bodies in the lateral EW nucleus in slice preparations. Slices were obtained from
      embryonic day 16 chicks, matching the age of the embryos in which calyces were
      studied. Recordings were localized to the lateral region of the EW nucleus using
      Lucifer yellow fills. Voltage-step commands from -70 to 0 mV produced calcium
      currents with both a sustained and an inactivating component. Depolarization
      steps to 0 mV from a holding potential of -40 mV eliminated the inactivating
      component. These recordings suggested the presence of both LVA and HVA calcium
      currents. Application of 0.1 mM NiCl2 produced a reversible decrease in the
      amplitude of the whole-cell calcium current, preferentially affecting the
      inactivating component. The Ni2+(-)sensitive current activated and inactivated
      rapidly in a voltage-dependent manner. Treatment with 0.1 mM cadmium chloride
      caused a reversible reduction in the amplitude of the calcium current.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7827987
TI  - Effect of cellular differentiation on nucleoside transport in human neuroblastoma
      cells.
AB  - The nucleoside transport characteristics of undifferentiated and differentiated
      LA-N-2 human neuroblastoma cells were compared through measurement of the
      cellular accumulation of [3H]formycin B in the absence and presence of specific
      nucleoside transport blockers such as dipyridamole and nitrobenzylthioinosine
      (NBMPR). [3H]NBMPR was also used as a high affinity probe to obtain an estimate
      of the number of NBMPR-sensitive nucleoside transport proteins. Undifferentiated
      LA-N-2 cells accumulated [3H]formycin B (25 microM) via a NBMPR/dipyridamole
      sensitive, Na(+)-independent, nucleoside transport system (Vi = 1.52
      pmol/microliters/s; maximum intracellular concentration = 45 pmol/microliters
      cell water). The undifferentiated cells also had a high density of site-specific
      [3H]NBMPR binding sites (135,000 sites/cell; KD = 0.4 nM). When cell
      differentiation was induced by exposure to a serum-free defined medium, the
      initial rate of transporter-mediated [3H]formycin B uptake increased to 1.92
      pmol/microliters/s, and the steady-state intracellular concentration of
      [3H]formycin B also increased significantly to 73 pmol/microliters. However,
      there was no concomitant change in the number of [3H]NBMPR binding sites, and the
      additional uptake was not Na(+)-dependent. This enhanced uptake in the
      differentiated cells appeared to be due, in part, to an increased functional
      expression of a NBMPR-resistant form of facilitated nucleoside transporter.
      Approximately 18% of the transporter-mediated uptake in the differentiated cells
      was resistant to inhibition by NBMPR at concentrations that blocked transport
      completely in the undifferentiated cells. This cell model may prove useful for
      basic studies on regulation of nucleoside transporter subtype expression in
      neural tissues, and for evaluation of the efficacy and potential host toxicity of
      cytotoxic nucleoside analogues (+/- specific transport blockers) in the treatment
      of neuroblastoma.

PMID- 7827988
TI  - Dynamic responses of presynaptic terminal membrane pools to electrical
      stimulation.
AB  - The anatomical tenets of the quantal-vesicular hypothesis of neurotransmission
      are a 1:1 ratio between numbers of releasable quanta and vesicles, a reciprocal
      response between vesicle and terminal membrane pools and constancy of the total
      membrane pool. We have used electrical stimulation and morphometry to study these
      relationships in the cholinergic presynaptic terminals of Torpedo electric organ.
      Our results show that during neurotransmission changes in vesicle numbers do not
      correlate with quantal release, vesicle and terminal membranes do not change in
      reciprocal fashion and total nerve terminal membrane does not remain constant. We
      conclude that these vesicular tenets of quantal release are not verifiable at the
      Torpedo electric organ junction.

PMID- 7827989
TI  - Effect of anoxia on glutamate formation from glutamine in cultured neurons:
      dependence on neuronal subtype.
AB  - Synthesis and release of glutamate formed from labeled glutamine were studied in
      primary cultures of the glutamatergic cerebellar granule cells and of the mainly
      GABAergic cerebral cortical neurons under anoxic conditions and under normoxic
      control conditions. Under both control and anoxic conditions cerebellar granule
      cells synthesized and released glutamate more intensely than cerebral cortical
      neurons, but this difference was enhanced under anoxic conditions. Thus, under
      normoxic conditions synthesis of intracellular labeled glutamate from glutamine
      was twice as high in cerebellar granule cell neurons as in cerebral cortical
      neurons during 30 min of incubation, but the release of newly synthesized labeled
      glutamate to the extracellular medium from cerebellar granule cell neurons was
      more than 4 times higher than the release from cerebral cortical neurons during
      30 min of incubation. Based on these observations it is suggested that a major
      reason for the increase in extracellular glutamate concentration during brain
      ischemia may be enhanced production and release of glutamate, especially in
      glutamatergic neurons.

PMID- 7827990
TI  - Enhanced neuropeptide Y release in the hippocampus is associated with chronic
      seizure susceptibility in kainic acid treated rats.
AB  - We measured the release of neuropeptide Y (NPY) from hippocampal slices of rats
      at various times after limbic seizures induced by a subcutaneous injection of 12
      mg/kg kainic acid (KA). Two days after KA, 100 mM KCl induced a 1.6 +/- 0.2-fold
      increase in NPY release compared to saline-injected rats (P < 0.05), while
      spontaneous and 50 mM KCl-induced release were unchanged. Thirty days after KA,
      the spontaneous and 100 mM KCl-induced efflux of NPY was enhanced 2-fold on
      average (P < 0.01) compared to controls, while no significant differences were
      found using 50 mM KCl. Tissue concentration of NPY was raised 2.2 +/- 0.2 times
      (P < 0.01) 30 days after KA. Thirty days after KA, the rats showed enhanced
      susceptibility to tonic-clonic seizures, assessed using a normally subconvulsive
      dose of pentylenetetrazol (PTZ; 30 mg/kg). A selective antibody (Ab) raised
      against NPY in a rabbit was infused bilaterally for three days in the CA3 area
      and dentate gyrus (DG) of the dorsal hippocampus of rats treated 30 days before
      with KA. This significantly reduced (P < 0.05) the number of animals with tonic
      clonic seizures induced by 30 mg/kg PTZ, compared to KA treated rats which
      received the inactivated Ab. The Ab was ineffective in naive rats injected with a
      full convulsive dose of PTZ (55 mg/kg). The present results show that neuronal
      release of NPY is enhanced in the hippocampus after limbic seizures induced in
      rats by KA. This effect persists for at least 30 days and may contribute to the
      chronically enhanced susceptibility to seizures after injection of this toxin.

PMID- 7827991
TI  - Short- and long-term effects of neonatal diazepam exposure on local cerebral
      glucose utilization in the rat.
AB  - The short- and long-term consequences of a neonatal exposure to diazepam (DZP) on
      the postnatal changes in local cerebral metabolic rates for glucose (LCMRglcs)
      were studied by the quantitative autoradiographic [14C]2-deoxyglucose method in a
      total number of 66 brain structures of freely moving rats. Rat pups received a
      daily subcutaneous injection of 10 mg/kg DZP, of the dissolution vehicle or of
      saline from postnatal day 2 (P2) to 21 (P21). The animals were studied at 4 ages,
      P10, P14, P21 and P60. DZP induced a decrease in LCMRglcs which was restricted to
      13 areas at P10, mainly sensory and limbic regions. At P14, the treatment had
      significant metabolic effects on 48 structures belonging to all functional
      systems. By P21, 23 brain areas were still affected by the treatment, mainly
      sensory, limbic and motor areas. At P60, i.e. at about 40 days after the end of
      drug exposure, LCMRglcs still decreased in 14 brain regions which were mainly
      sensory and limbic structures. The structures most sensitive to both short- and
      long-term consequences of the anticonvulsant treatment are mammillary body,
      limbic cortices and sensory regions. The dissolution vehicle increased LCMRglcs
      in a few brain regions at P14 and P60, whereas it decreased metabolic levels in 5
      brain regions at P21. The results of the present study show that the brain
      appears to be particularly vulnerable to the treatment at P14, period of active
      brain growth, whereas by P21, the drug is actively metabolized and a tolerance to
      the treatment may occur. The long-term effects of the treatment are in good
      accordance with the well-known effects of DZP on anxiety, sedation and memory.
      The structures most sensitive to early neonatal DZP exposure are the mammillary
      body, limbic cortices and sensory regions that all contain a high density of
      benzodiazepine binding sites.

PMID- 7827992
TI  - Methylmercury-induced augmentation of oxidative metabolism in cerebellar neurons
      dissociated from the rats: its dependence on intracellular Ca2+.
AB  - Effect of methylmercury chloride on oxidative metabolism of cerebellar neurons
      dissociated from the rats was examined using 2',7'-dichlorofluorescin (DCFH)
      which is oxidized by cellular hydrogen peroxide to be a fluorescent compound
      (DCF) and fluo-3, an indicator for intracellular Ca2+ concentration ([Ca2+]i).
      Methylmercury at 1 microM or less did not affect DCF fluorescence of cerebellar
      neurons. Further increase in concentration of methylmercury (up to 30 microM)
      induced changes in DCF fluorescence. Thus, DCF fluorescence was slightly
      attenuated during 5 min after applying methylmercury to the neurons, indicating a
      decrease in oxidation of DCFH. Thereafter, DCF fluorescence was time-dependently
      augmented in continued presence of methylmercury, indicating an increase in DCFH
      oxidation. Although methylmercury-induced augmentation of DCF fluorescence was
      greatly suppressed under external Ca(2+)-free condition, it was not the case for
      methylmercury-induced attenuation of DCF fluorescence. Methylmercury at 3 microM
      or more dose-dependently increased the [Ca2+]i. Results suggest that
      methylmercury increases intracellular Ca2+ in cerebellar neurons, resulting in an
      increase in formation of reactive oxygen species that may contribute to cell
      injury.

PMID- 7827993
TI  - Effect of N,N-diethyldithiocarbamate on ionomycin-induced increase in oxidation
      of cellular 2',7'-dichlorofluorescin in dissociated cerebellar neurons.
AB  - Effect of N,N-diethyldithiocarbamate (DDC), an inhibitor for cytosolic superoxide
      dismutase, on an ionomycin-induced increase in oxidative metabolism was examined
      in cerebellar neurons dissociated from the rats, using a flow cytometer and 2',7'
      dichlorofluorescin diacetate and fluo-3-AM, fluorescent dyes for intracellular
      hydrogen peroxide and Ca2+, respectively. DDC reduced the ionomycin-induced
      augmentation of 2',7'-dichlorofluorescin fluorescence in a dose-dependent manner.
      DDC did not affect cellular content of 2',7'-dichlorofluorescin and ionomycin
      induced increase in intracellular Ca2+ concentration. Results indicate that
      ionomycin increases the formation of superoxide anion in brain neuron.

PMID- 7827994
TI  - Increased threshold concentrations of neuropeptide Y for a stimulatory effect on
      food intake in obese Zucker rats--changes in the microstructure of the feeding
      behavior.
AB  - A central dysregulation of several neuropeptides could be at the origin of the
      marked hyperphagia of the obese Zucker rat, a well-known animal model used for
      the study of obesity. Neuropeptide Y (NPY), which strongly stimulates food intake
      and increases early in life in obese rats, plays a major role in the development
      of this hyperphagia. The aim of our experiment was to measure the feeding
      responses of lean (n = 8) and obese (n = 17) male Zucker rats to several doses of
      exogenous NPY injected in the lateral brain ventricle. We analyzed the
      microstructure of the rats' feeding behavior with an automatic device for 8 h
      post-injection. NPY stimulated food intake both in the lean and obese rats in a
      dose-dependent manner (P < 0.001). However, the minimal effective dose was always
      3-4 times greater in the obese rats than in the lean ones (range: 0.43-0.53 vs.
      0.12-0.18 microgram/brain; P < 0.001). Meal size, meal duration and time spent
      eating significantly increased in the lean rats (P < 0.05 or less). The last two
      parameters also increased in the obese rats but with the highest dose (5
      micrograms) only. The obese Zucker rats were therefore less sensitive to NPY than
      the lean ones, probably because of their already high endogenous NPY levels. The
      modifications in the eating behavior indicate that NPY could overcome the satiety
      signals.

PMID- 7827995
TI  - Hippocampal mossy fiber distributions and intermale aggression in seven inbred
      mouse strains.
AB  - The capacity to initiate attack behavior against a passive standard opponent was
      measured in 140 male mice belonging to seven different inbred mouse strains.
      Large strain differences were found, which strongly correlated with the size of
      the hippocampal intra- and infrapyramidal mossy fibers terminal fields. These
      results, combined with those obtained from earlier experiments, point to a
      possible modulating role of the hippocampus in the regulation of attack behavior
      in male mice.

PMID- 7827996
TI  - Reciprocal modulation of corticotropin-releasing factor and interleukin-1
      receptors following ether-laparotomy stress in the mouse.
AB  - Ether-laparotomy stress resulted in a dramatic decrease in specific iodine-125
      labeled ovine CRF binding ([125I]oCRF) in the pituitary at 6 h after the onset of
      the stress although it did not affect [125I]oCRF binding in the pituitary at 2 h
      after the stress. [125I]oCRF binding was unchanged in the frontal cortex after
      the stress. In contrast, [125I]interleukin-1 (IL-1)alpha binding was
      significantly increased in the pituitary at 2 h after the stress and tended to be
      higher than non-stressed levels at 6 h after the stress but was not statistically
      significant. Ether-laparotomy stress did not affect [125I]IL-1 alpha binding in
      hippocampus, spleen and testis at any time after the stress. Plasma
      adrenocorticotropic hormone (ACTH) and corticosterone were increased at 2 h after
      the stress. These data demonstrate complex interactions between CRF and IL-1
      receptors on HPA axis during stress.

PMID- 7827997
TI  - Evidence in support of nitric oxide (NO) involvement in the cyclic release of
      prolactin and LH surges.
AB  - Studies were undertaken to determine whether nitric oxide (NO) is involved in
      induction of the prolactin surge on proestrus and in that induced by ovarian
      steroids in ovariectomized (ovx) rats, by using inhibitors of NO synthase, the
      enzyme that generates NO. Two week-ovariectomized rats were treated either with
      estradiol benzoate (EB, 30 micrograms/rat, s.c.) alone, or with EB and 2 days
      later with progesterone (P, 2 mg/rat, s.c.) to evoke a prolactin surge in the
      afternoon. Injections of the NO synthase inhibitor Nw-nitro-L-arginine methyl
      ester (40 mg/kg, s.c.) at 10.000, 12.00, and 14.00 h completely suppressed the
      steroid-induced prolactin surge in the afternoon. Similarly, another NO synthase
      inhibitor, Nw-nitro-L-arginine (100 mg/kg, s.c.), injected at 1000, 1200, and
      1400 h on proestrus suppressed prolactin and luteinizing hormone (LH) surges, but
      failed to alter the daily increase of corticosterone. These studies confirm our
      earlier report and show that NO is involved in the complex processes that
      initiate the afternoon prolactin and LH surges of proestrus.

PMID- 7827998
TI  - The role of opioids in newborn pig fluid percussion brain injury.
AB  - The present study was designed to characterize the relationship between cerebral
      opioid concentration, cerebral hemodynamics, and cerebral oxygenation following
      percussion brain injury in neonatal pigs. Previous research found that opioids
      represent a significant vasoactive component in the regulation of the neonatal
      piglet cerebral circulation. Anesthetized newborn (1-5 days old) pigs equipped
      with a closed cranial window were connected to a percussion device consisting of
      a saline-filled cylindrical reservoir with a metal pendulum. Brain injury of
      moderate severity (1.9-2.3 atm.) was produced by allowing the pendulum to strike
      a piston on the cylinder. Fluid percussion brain injury decreased pial arteriolar
      diameter (132 +/- 5 to 110 +/- 5 microns within 10 min). Cerebral blood flow also
      fell within 10 min of injury and continued to fall progressively for 3 h,
      resulting in a 46 +/- 4% decrease. Within 30 s of brain injury, there was a
      transient increase in cerebral hemoglobin-O2 saturation that was reversed to a
      progressive profound decrease in cerebral hemoglobin-O2 saturation for the next 3
      h, as measured by near infrared spectroscopy. CSF opioid concentrations were
      increased 10 min after brain injury; dynorphin showed the largest proportional
      increase (5.8 +/- 0.9 fold). The CSF concentration for other opioids continued to
      increase over 180 min while the dynorphin concentration progressively decreased
      with time. In naloxone (1 mg/kg i.v.) pretreated piglets, the brain injury
      induced decrease in arteriolar diameter was attenuated (129 +/- 5 to 121 +/- 5
      microns within 10 min). Similarly, the decrease in regional cerebral blood flow
      and cerebral hemoglobin-O2 saturation observed following brain injury were also
      blunted by naloxone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7827999
TI  - Differential changes in the activities of multiple protein kinase C subspecies in
      the hippocampal-kindled rat.
AB  - In previous studies we demonstrated that the membrane-associated protein kinase C
      (PKC) activities in the right and left hippocampus (HIPP) of rats kindled from
      the left HIPP increased significantly 4 weeks and 4 months after the last seizure
      compared with those in matched control rats. In this study, we investigated the
      long-lasting effect of HIPP-kindling on the membrane-associated activities of PKC
      subspecies in the bilateral HIPP 1 and 4 weeks after the last generalized kindled
      seizure had occurred. The membrane-associated activities of PKC subspecies were
      found to be subject to differential regulation. The activity of the alpha
      subspecies was unchanged, whereas the respective activities of the beta- and
      gamma-subspecies in the kindled group increased significantly, compared with the
      controls, one (21%, P < 0.0001 for the beta-subspecies, and 23%, P < 0.001 for
      the gamma-subspecies) and 4 weeks (19%, P < 0.02 for the beta-subspecies, and
      19%, P < 0.05 for the gamma-subspecies) after the last seizure. There were no
      significant differences in cytosolic PKC activity between the control and kindled
      groups for any subspecies examined at either time after the last seizure. These
      results suggest that activation of the PKC beta- and gamma-subspecies may play an
      important role in the enduring seizure susceptibility associated with kindling.

PMID- 7828000
TI  - Quantitative mapping of cytochrome oxidase activity in the central auditory
      system of the gerbil: a study with calibrated activity standards and metal
      intensified histochemistry.
AB  - The objective was to obtain detailed topographic determinations of cytochrome
      oxidase activity in the gerbil central auditory system at the light microscopic
      level. Quantitative techniques were developed using (1) tissue standards
      calibrated to express histochemical measures as actual enzyme activity units, (2)
      densitometry and image analysis of histochemical reaction product formation, (3)
      spectrophotometry of cytochrome oxidase activity, and (4) a cobalt-intensified
      staining procedure compatible with autoradiography and other techniques requiring
      fresh-frozen brains without perfusion-fixation. Linear relationships between
      incubation time, section thickness, and activity of dissected brain regions, with
      their reaction product measured densitometrically were determined. Auditory
      structures with the high activities showed about 8 times the labeling intensity
      of the white matter or control sections inhibited with cyanide, glutaraldehyde,
      or heat. This indicated the high sensitivity of the method without loss of
      specificity. Specific activity for each of the 18 auditory structures measured
      were all above the units measured for whole brain homogenates, supporting the
      notion that basal levels of oxidative metabolism are greater for the auditory
      system. There was a progressive decrement in activity from brain stem to
      forebrain auditory structures. The more peripheral nuclei also showed a higher
      proportion of somatic as compared to neuropil reactivity. In contrast, auditory
      midbrain and thalamocortical regions were characterized primarily by neuropil
      reactivity. Comparison of intrinsic patterns of activity with morphological
      schemes to subdivide nuclei, showed a good correspondence with classical
      subdivisions derived from Golgi studies. The reported activities may provide a
      base of normative data in the gerbil for subsequent studies of central auditory
      functions. The method presented fulfilled established quantitative criteria and
      provided a more sensitive approach for regional mapping studies of brain
      cytochrome oxidase activity.

PMID- 7828001
TI  - Electroconvulsive shock increases interstitial concentrations of uric acid in the
      rat brain.
AB  - This study examined the effects of electroconvulsive shock (ECS) on striatal
      interstitial concentrations of the purine metabolite uric acid (UA) using
      microdialysis in freely moving rats. UA increased to about 200% of baseline
      following ECS. Intense seizure activity induced by the convulsant agent flurothyl
      also resulted in a two-fold increase of UA concentrations suggesting that the ECS
      induced UA increase is related to the seizure activity per se. Local
      administration of tetrodotoxin or perfusion with a Ca(2+)-free solution failed to
      affect the basal or the ECS-induced increase in UA concentrations. These data
      indicate that both the basal and the stimulated interstitial concentrations of
      uric acid are not dependent upon neuronal activity and exocytotic release. The UA
      response to ECS appears to be refractory to a second ECS delivered 2 but not 24 h
      after the first. Intrastriatal infusion of allopurinol (1 mM), an inhibitor of UA
      synthesis, decreased basal UA concentrations to 26% but did not influence the ECS
      induced UA increase. Systemic injection of allopurinol (20 mg/kg, i.p.) decreased
      basal UA concentrations to 25% and prevented the ECS-induced UA elevation. ECS
      also increased serum concentrations of UA to almost 200% of baseline. Allopurinol
      (20 mg/kg, i.p.) markedly decreased serum UA concentrations to non-detectable
      levels and completely abolished the ECS-induced increase. The estimated
      concentration difference between blood and brain interstitial UA strongly
      suggests that ECS-induced increase in brain interstitial UA concentrations is of
      peripheral origin possibly due to disruption of the blood brain barrier during
      seizure activity.

PMID- 7828002
TI  - Selective reduction of hippocampal dentate frequency-potentiation in striatally
      lesioned rats with impaired place learning.
AB  - The induction of hippocampal frequency-potentiation (i.e. post-tetanic
      potentiation (PTP) and long-term potentiation (LTP) was analyzed in rat
      hippocampal slices obtained from animals showing impaired place learning in the
      Morris water maze as a consequence of bilateral striatal injection of quinolinic
      acid. Vehicle-injected animals, showing normal performances in the Morris water
      maze, behaved as controls. After the application of an electrical tetanus (1 s,
      100 Hz, 50 microA) in the stratum radiatum, no significant differences were found
      in the percent of induction of both PTP and LTP in the CA1 area of hippocampal
      slices obtained from lesioned and sham-operated rats. After the application of an
      electrical tetanus (1 s, 100 Hz 50 microA) in the stratum moleculare, a
      significant difference was found in the percent of dentate PTP induction in
      hippocampal slices obtained from lesioned and sham-operated rats. Specifically,
      dentate PTP induction was significantly (P < 0.01) higher in slices obtained from
      sham-operated rats with a good performance in the Morris water maze than in
      slices obtained from striatally lesioned rats, which had shown poor performance
      in the Morris water maze. On the contrary, no significant differences were found
      in the percent of dentate LTP in hippocampal slices obtained from rats of the two
      groups. The data demonstrate that the impairment of the place learning in
      striatally lesioned rats is associated with a selective reduction of hippocampal
      dentate frequency-potentiation.

PMID- 7828003
TI  - Architectural alterations in rat cerebral microvessels after hypobaric hypoxia.
AB  - We performed 3-dimensional studies of vascular casts of the microvasculature of
      the cerebral cortex of rats that were exposed to three weeks of hypobaric hypoxia
      and of control rats. Scanning electron microscopy of the casts gave the
      qualitative impression of increased vascularity of the cerebral cortex,
      particularly the deeper layers, in hypoxic rats. Quantitative analysis of
      capillary segment lengths revealed a significant shift in the frequency
      distribution to longer lengths (from 77 +/- 8 to 90 +/- 14 microns) in the deep,
      but not in the superficial, layers of the cerebral cortex of hypoxic rats. These
      findings agree with previous results reporting increased capillary density in the
      brain after exposure to prolonged hypobaric hypoxia and suggest that capillary
      segment elongation plays a role in the increased capillary density in the deeper
      layers of the cerebral cortex.

PMID- 7828004
TI  - Degeneration of nigrostriatal dopaminergic neurons increases iron within the
      substantia nigra: a histochemical and neurochemical study.
AB  - Parkinson's-diseased (PD) brains have increased levels of iron in the zona
      compacta of the substantia nigra (SNc). To determine whether these elevated
      nigral iron levels may be caused secondarily by degeneration of nigrostriatal
      dopaminergic (NS-DA) neurons, the NS-DA pathway was unilaterally lesioned in rats
      through 6-hydroxydopamine (6-OHDA) infusion and nigral iron levels evaluated
      three weeks later. A significant increase was observed in both iron concentration
      (+35%) and iron content (+33) within the substantia nigra (SN) ipsilateral to
      comprehensive 6-OHDA lesions. Moreover, ferric iron staining was dramatically
      increased within the SNc following 6-OHDA lesions, primarily due to the
      appearance of iron-positive SNc neurons and infiltrating reactive glial cells.
      Iron staining in the SN zona reticularis was modestly increased after 6-OHDA
      lesions, but staining in the neostriatum and globus pallidus was unaffected.
      These results indicate that loss of NS-DA neurons is associated with increased
      iron levels in the SN. This suggests that increased nigral iron levels in PD may
      be secondary to some neurodegenerative process. Nonetheless, even a secondary
      increase in nigral iron levels may be of pathogenic importance in PD because of
      iron's ability to catalyze neurotoxic free radical formation and perpetuate
      neurodegeneration.

PMID- 7828005
TI  - Enhanced calcium signalling events in neuroblastoma x glioma hybrid NG108-15
      cells after treatment with dibutyryl cyclic AMP.
AB  - The effects of dibutyryl cyclic AMP (dbcAMP) treatment on Ca2+ channel
      activities, Ca2+ accumulation by intracellular Ca2+ pools, and sizes of IP3- and
      GTP-releasable pools in neuroblastoma x glioma hybrid NG108-15 cells were
      studied. High extracellular K+ induced a greater rise in intracellular calcium
      concentration ([Ca2+]i) in dbcAMP-treated cells than in control cells. In dbcAMP
      treated cells, the initial phase of the high K(+)-induced [Ca2+]i rise displayed
      a much higher sensitivity to omega-conotoxin than it did in control cells,
      whereas the plateau phase of the [Ca2+]i rise was sensitive only to nifedipine.
      These results indicate that predominantly L-type Ca2+ channels exist in control
      cells, and that N-type channels develop only after dbcAMP treatment. In dbcAMP
      treated cells, mitochondria showed an increased Ca2+ uptake capacity (5.3 nmol
      Ca2+/mg protein) compared with that in control cells (4.2 nmol Ca2+/mg protein).
      However, dbcAMP treatment did not cause significant change in the affinity for
      Ca2+. Dibutyryl cAMP treatment enhanced the Ca2+ accumulation activity by
      nonmitochondrial pools (from 0.84 to 0.97 nmol Ca2+/mg protein) and increased the
      affinity for Ca2+ (EC50 for Ca2+ decreased from 0.146 microM to 0.063 microM).
      Our data also indicate that the pool that is sensitive to both IP3 and GTP was
      enlarged. The affinities for IP3 and GTP in causing Ca2+ release remained the
      same before or after dbcAMP treatment.

PMID- 7828006
TI  - Focal traumatic brain injury causes widespread reductions in rat brain
      norepinephrine turnover from 6 to 24 h.
AB  - The effect of right sensorimotor traumatic brain injury (TBI) in male Sprague
      Dawley rats on brain norepinephrine (NE) turnover was assessed by measuring the
      decline of endogenous NE levels following tyrosine hydroxylase inhibition
      produced with alpha-methyl-p-tyrosine. Right sensorimotor cortex contusions were
      produced by a pneumatically driven piston which depressed the dural surface by 2
      mm at 3.2 m/s. TBI rats were compared to uninjured, anesthetized controls at 6 h
      and 24 h after surgery. While NE turnover was not affected at the lesion site at
      6 h after TBI, it was either abolished or decreased by 33-75% bilaterally in the
      hypothalamus and in the cerebral cortex surrounding and rostral to the lesion
      site. In the cortex caudal to the lesion site, NE turnover was completely
      abolished. NE turnover in cerebral cortex opposite the lesion site and in the
      contralateral cerebellum was decreased by 51 and 43%, respectively, at 6 h. At 24
      h, NE turnover was either abolished or decreased bilaterally by 45-92% in all
      cortical areas, in the hypothalamus, cerebellum, locus coeruleus and medulla.
      Thus, right sensorimotor cortex contusion causes a marked, early and widespread
      depression of brain NE turnover. Since amphetamine increases NE turnover, this
      may explain the dramatic improvement in behavioral deficits which occurs
      following amphetamine administration at 24 h after such lesions.

PMID- 7828007
TI  - Hormonal and metabolic effects of paraventricular hypothalamic administration of
      neuropeptide Y during rest and feeding.
AB  - To investigate the role of neuropeptide Y (NPY) in the paraventricular nucleus of
      the hypothalamus (PVN) in the regulation of autonomic outflow, hormonal (plasma
      insulin and catecholamines), metabolic (blood glucose and plasma free fatty
      acids) and cardiovascular (heart rate and main arterial pressure) indices were
      measured before, during, and after bilateral infusion of NPY (1.0, 0.2, 0.04
      micrograms in 1 microliter synthetic CSF) into the PVN of conscious resting rats.
      Administration of the highest dose (1.0 microgram/microliter) caused bradycardia
      and reduced circulating norepinephrine levels without effecting circulating
      fuels, insulin or epinephrine. In a second experiment, feeding-induced changes in
      hormonal and metabolic indices were assessed after NPY administration (1.0
      microgram/microliter) into the PVN. During and after feeding, NPY enhanced the
      feeding-induced insulin response (P < 0.01) and attenuated the feeding-induced
      norepinephrine response (P < 0.05). The results of the present study suggest that
      stimulation of NPY receptors in the PVN decreases sympathetic activity and
      increases parasympathetic activity in resting conditions, and that these effects
      are potentiated during feeding.

PMID- 7828008
TI  - Behavioural expression of laying hens in aviaries and cages: frequencies, time
      budgets and facility utilisation.
AB  - 1. We studied: behavioural frequencies and time budgets of behaviour patterns in
      non-beak-trimmed White Leghorn layers housed in cages (720 cm2/hen, 3 hens/cage),
      and in the Marielund, the Tiered Wire Floor (TWF), and the Laco-Voletage aviaries
      (17 hens/m2 ground area); individual variation in behaviour among aviary hens;
      spatial utilisation of the different types of aviary. 2. At 25, 40, and 60 weeks
      of age behaviour patterns of 114 focal animals were data logged. Each bird was
      observed for 10 min 4 times a day on three consecutive days. 3. The frequency of
      activity transitions and the activity level was highest in TWF, second highest in
      cages, and lowest in Laco-Voletage, suggested that Laco-Voletage hens were the
      calmest, whereas birds in cages and in TWF were more restless. Abnormal types of
      behaviour occurred most often in cages and TWF. The disadvantageous behaviour
      patterns shown by birds in TWF and cages imply that these environments were the
      least appropriate for this layer strain. 4. Pronounced individual variations in
      mobility and facility utilisation were found, both within and between the three
      aviaries. Resting levels were used twice as much (Laco-Voletage), and litter
      areas one third as much (Marielund), as that expected on a simple a proportionate
      basis. Most feather pecking was performed at resting levels and on feeding
      floors, whereas most agonistic behaviour patterns were observed on feeding floors
      and litter. 5. Measures to improve the aviaries are outlined.

PMID- 7828009
TI  - Genetic parameters from factorial cross breeding in two duck strains (anas
      platyrhynchos) Brown Tsaiya and Pekin, for growth and fatty liver traits.
AB  - 1. A total of 655 mule ducklings were produced in three hatches by artificial
      insemination of common duck females Brown Tsaiya and Pekin "Alienor" and of their
      2 reciprocal crossbreds with Muscovy semen. 2. They were fed ad libitum until 6
      weeks, then restricted to one meal per day until day 75 and afterwards preforce
      fed until day 84 and subsequently forced fed by 2 crammers, twice a day, from the
      age of 85 d and for a maximum of 13 d. 3. Body weight at hatching, 28 d, 56 d, 75
      d, 84 d and at slaughter, the number of force-fed meals, the "paletot" weight,
      the fatty liver weight, the fat release rate after sterilisation of a 60 g
      portion of liver and the serous melting rate were measured individually. 4.
      Significant dam genotype and hatch effects were present for all traits. The
      crammer effect on force feeding traits was also significant. For mule ducks from
      Brown Tsaiya, Tsaiya x Pekin, Pekin x Tsaiya and Pekin dams respectively, mean
      body weight was 2356, 3219, 3137 and 3801 g at 12 weeks, "paletot" weight was
      1585, 2111, 2110 and 2470 g, fatty liver weight was 441, 585, 563 and 641 g, fat
      release rate was 35.1, 40.5, 38.2 and 46.0%. 5. The estimated differences between
      Pekin and Tsaiya genetic effects in their mule progeny were significant and in
      favour of the Pekin, except for the number of force fed meals and for the serous
      melting rate.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7828010
TI  - Microbiological and shelf life assessment of chilled eviscerated whole chicken
      broilers in Saudi Arabia.
AB  - 1. The microbiological quality and shelf life of chicken carcasses marketed in
      Riyadh, Saudi Arabia were assessed. 2. The mean initial microbial counts (log10
      count/cm2) were 4.67, 4.14, 2.21, 2.78 and 2.96 for total aerobes, psychrotrophs,
      coliforms, Staphylococcus aureus and yeasts and moulds, respectively; these
      counts suggest a moderate level of contamination during processing. 3. Yeasts and
      moulds were present in relatively large numbers and constituted a considerable
      portion of the spoilage flora. 4. The mean shelf life of chicken broilers was
      9.6, 6 and 4.4 d at 4, 7 and 10 degrees C, respectively. Storage at 4 degrees C
      resulted in better keeping than storage at 7 degrees C or 10 degrees C, while
      there was no significant difference between 7 degrees and 10 degrees C. 5. The
      initial total of aerobes, psychrotrophs and yeasts and moulds were found to
      negatively correlate with shelf life.

PMID- 7828011
TI  - Nutritive value of triticale fed to cockerels and chicks.
AB  - 1. The chemical composition, and amino acid and starch bioavailabilities of 18
      triticale varieties were studied. In addition, the water soluble pentosan (WSP)
      content of 8 varieties was determined. 2. A wide variation in protein (149 to 203
      g/kg DM), starch (563 to 629 g/kg DM) and WSP (27.7 to 50.9 g/kg DM) was found
      between varieties. 3. The TMEn reproductibility was assessed in two laboratories,
      using Leghorn cockerels, Isabrown cockerels and 3-week-old chicks. There were no
      significant differences in the TMEn values (range 14.0 to 15.2 MJ/kg DM) between
      the two types of cockerel. The TMEn values of the varieties were similar for
      chicks (range 13.6 to 14.9 MJ/kg DM) and for cockerels, with the exception of one
      variety. 4. The bioavailability of starch (range 96.5 to 99.4%) of some varieties
      was higher for cockerels than for chicks. The mean bioavailability of amino acids
      for cockerels was 94.5%. 5. TMEn prediction equations were derived from the
      chemical composition of the varieties. Best-fit equations were obtained for
      starch (R2 = 0.62, RSD = 0.24), ash (R2 = 0.58, RSD = 0.25) and WSP (R2 = 0.52,
      RSD = 0.27).

PMID- 7828012
TI  - Xylanase in broiler diets with differences in characteristics and content of
      wheat.
AB  - 1. Experiments were conducted to measure the effect of xylanase supplementation
      on the performance of broilers fed on wheat-based diets containing high and low
      extract viscosity wheat (experiment 1), baking and feeding quality wheat
      (experiment 2) and with variation in wheat content (experiment 3). 2. Xylanase
      supplementation improved food conversion ratios by 2.2-2.9% and body weight gain
      by 0.2-2.5%. This was independent of wheat characteristics but slightly dependent
      on the wheat content of the diet. These effects were related to a lowering of
      digesta viscosity. 3. Differences in extract viscosity of wheat were not
      reflected in broiler digesta viscosity. 4. Reduction of digesta viscosity
      resulted in only a slight improvement of litter score. Reduced intestinal
      viscosity decreased relative pancreas weight and to a lesser extent relative
      small intestinal weight. 5. Baking quality wheat Baldus gave better performance
      than the feed quality wheats Apollo and Slejpner. 6. It was concluded that
      xylanase supplementation of wheat-based diets invariably had a positive effect on
      broiler performance.

PMID- 7828013
TI  - Response of broiler chicks to threonine-supplemented diets to 4 weeks of age.
AB  - 1. Two experiments were carried out to determine the response of broiler chicks
      to threonine-supplemented diets between 10 and 28 d and 7 and 21 d of age,
      respectively. 2. In the first experiment female broiler chicks were fed on 11
      experimental diets. Two iso-energetic basal diets (diets 1 and 2) were prepared
      with 200 and 160 g CP/kg and 7.6 and 6.0 g threonine/kg respectively. Both diets
      contained 11.5 g lysine and 8.7 g sulphur-containing amino acids/kg. Diet 3 was
      composed of diet 2, supplemented with all essential and non-essential amino acids
      (EAA and NEAA, respectively) except threonine, to the concentrations of the amino
      acids in diet 1. The NEAA were added as a combination of glutamic acid and
      glycine. Diets 4 to 11 had the same compositions as diet 3, but contained
      increasing amounts of threonine. 3. For birds fed on diet 2, gain was
      significantly lower and food/gain ratio was significantly higher than for birds
      fed on diet 1. Supplementation with EAA, NEAA and threonine to the same
      concentrations in diet 1 resulted in a performance similar to that found on diet
      1. 4. In experiment 2, male and female broiler chicks both received 10
      experimental diets. Diet 1 contained 220 g CP/kg and 8.5 g threonine/kg, diet 2
      contained 160 g CP/kg from natural raw materials and 6 g threonine/kg. Both diets
      contained 12.4 g lysine and 9.3 g sulphur-containing amino acids/kg. Basal diet 2
      was supplemented with all EAA and NEAA to the concentrations of basal diet 1,
      except for threonine. Diets 3 to 10 had the same compositions as the supplemented
      diet 2, but contained increasing amounts of threonine. 5. For male and female
      chicks on diet 2, gain was significantly lower and food/gain ratio significantly
      higher than those on diet 1. Diet 10 (160 g CP/kg plus all EAA, including
      threonine, and NEAA supplemented to the concentrations of diet 1) resulted in the
      same performance as diet 1. 6. The results indicate that, when low protein maize
      soyabean meal diets supplemented with EAA and NEAA with 13.31 MJ ME/kg were fed
      to male and female broiler chicks until 21 d of age, improvements in gain and
      food/gain ratio were obtained when the dietary threonine content was increased to
      7.25 g/kg. When female chicks were fed threonine-supplemented diets to 28 d of
      age, improvement in gain and food/gain ratio was obtained when the threonine
      concentrations were increased to 6.32 g/kg diet.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7828014
TI  - Effects of dietary mineral supplementation on the performance and mineral
      retentions of broilers at high ambient temperatures.
AB  - 1. The relationship between broiler performance and two dietary mineral balance
      equations was investigated at a high constant ambient temperature (30 degrees C)
      using a range of 11 salt supplements given to male broiler chicks from 21 to 42 d
      of age. 2. No relationship was found between broiler performance and either of
      the two balance equations. 3. Re-evaluating these equations using retained,
      rather than dietary, mineral concentrations did not improve the relationship
      although changes in mineral retentions associated with the supplements indicated
      that dietary concentrations were not a good indicator of the impact of the diet
      on the bird's acid-base homoeostasis. 4. Evidence was found that metabolisable
      anions supplemented in association with mineral cations may have a significant
      effect on broiler performance.

PMID- 7828015
TI  - Attempts to achieve low-weight broiler breeder hens by severe growth depression
      during various periods up to 6 weeks of age and food allocation below the
      recommendations thereafter.
AB  - 1. Three experiments were carried out with White Rock (Anak) female chicks to
      evaluate the possibility of obtaining low-weight breeder hens and to assess their
      reproduction potential. Such hens were obtained by early growth depression
      induced by either severe food restriction (SFR) from 1 or 2 to 3 or 4 weeks of
      age, or a low-protein diet (LPD) fed from 0 to 6 weeks of age, or the use of
      diets containing 0.7 or 0.8% zinc as ZnO from 1 to 3 weeks of age, followed by
      food allocation below recommendation up to 22 or 67 weeks of age. 2. Body weights
      (BW) of the birds whose growth had been depressed were consistently and at time
      significantly lower than those of the control birds throughout the experiments.
      Age at first egg was delayed in hens previously fed the LPD and the diet
      containing the higher concentration of ZnO, and in those exposed to SFR from 2 to
      4 weeks of age. BW at that time tended to be lower in birds whose growth had been
      depressed, although a significant effect was observed in only one experiment. 3.
      Egg production and egg size were not significantly affected by the various
      treatments, except for the lower production in hens fed the LPD at an early age.
      4. Negative regressions (on an individual basis) were consistently observed
      between BW at 22 weeks of age and age at first egg, and between age at first egg
      and number of eggs laid. Positive regressions were observed between age at first
      egg and BW at that time. The regressions between BW at 22 weeks of age and number
      of eggs laid were positive but not always significant. 5. Severe growth
      depression at an early age (produced by food restriction or ZnO supplemented
      diet, but not LPD) followed by decreased allocation of food afterwards, could
      provide a means for reducing BW of broiler breeder hens without adversely
      affecting egg production. This procedure may save 2.5 to 6.6% of the food
      consumed during the life span of the birds.

PMID- 7828016
TI  - Effect of dietary energy restriction on retention of protein, fat and energy in
      broiler chickens.
AB  - 1. Broiler chickens were fed 60-100% of recommended energy intakes to study the
      effects of energy restriction on protein and fat retention. 2. At an energy
      retention of 179 kJ/kg W0.75 d, only protein was retained. At higher energy
      intakes, each increment in retention had a rather constant composition: about 85%
      energy in fat and 15% in protein. At lower energy intakes body fat was mobilised
      whereas protein was deposited. 3. The efficiencies of energy retention in protein
      and fat were estimated to be 0.66 and 0.86 respectively. 4. The rather constant
      composition of additional retained energy after additional energy supply provides
      an explanation for a linear relationship between energy intake and energy
      retention.

PMID- 7828017
TI  - Concentrations of antisecretory factor in eggs and in chicken blood plasma.
AB  - 1. In the present study, the concentration of antisecretory factor (ASF), a
      lectin with hormone-like properties, and with the capacity to regulate water and
      electrolyte transport in the small intestine, was higher in hen's egg yolk than
      in egg white (1.20 v. 0.46 units/ml). 2. The blood plasma concentrations of ASF
      activity were higher in d-old chicks (1.03 units/ml) than in 7-d-old (0.42
      units/ml) or 21-d-old birds (0.18 units/ml); the contents were found to be high
      again in 35-d-old chickens, but to have decreased by 60 to 90% after transport to
      slaughter 1 day later. 3. The amount of ASF activity was lower in two groups of
      chickens manifesting patent loose droppings at slaughter (0.15 units/ml in one
      group, and 0.08 units/ml in the other), than in two groups with normal faecal
      consistency (0.65 units/ml in one group, and 0.72 units/ml in the other). 4. The
      results demonstrate the presence of ASF in eggs, and a variation of ASF activity
      in chickens blood plasma in relation to age, stress and faecal consistency. The
      interpretation of these data suggests a regulatory influence of ASF on chicken
      intestinal transport of water.

PMID- 7828018
TI  - Effect of selected dietary antioxidants on fatty liver-haemorrhagic syndrome in
      laying hens.
AB  - 1. Single comb White Leghorn hens of an inbred line highly susceptible to fatty
      liver haemorrhagic syndrome (FLHS) were fed supplemented dietary ascorbic acid
      (200 mg/kg), alpha-tocopherol (75 mg/kg), or L-cysteine (3 g/kg, and 6 g/kg) for
      28 d in order to evaluate the potential therapeutic effect of these compounds
      against the disease. 2. Supplementation of ascorbic acid, alpha-tocopherol, or a
      low level of L-cysteine (3 g/kg) did not significantly affect any of the hepatic
      variables evaluated. Hepatic glutathione was not increased by the supplementation
      of dietary L-cysteine. 3. L-cysteine supplemented at a level of 6 g/kg decreased
      hepatic dry matter and fat contents without affecting the hepatic malondialdehyde
      or the liver haemorrhagic score. 4. Because one of the predisposing factors of
      FLHS is a high hepatic fat content it was concluded that dietary supplementation
      of L-cysteine (6 g/kg) may be useful in the prevention of the disease.

PMID- 7828019
TI  - Variation in plasma cholesterol concentration over time in the domestic fowl.
AB  - 1. Variations in the concentration of plasma cholesterol available to the
      developing oocyte over a three week period in Gallus domesticus are described. 2.
      There are small changes in concentration between weeks for individual birds, but
      no changes between consecutive days within weeks or times within days. 3. It is
      recommended that future attempts to assess the relationship between variation in
      blood and yolk cholesterol concentrations estimate blood cholesterol
      concentration from two samples taken a week apart.

PMID- 7828020
TI  - The effects of semi-purified diets on growth and condition of Sepia officinalis
      L. (Mollusca: Cephalopoda).
AB  - The effects of five different surimi diets (fish myofibrillar protein
      concentrate) on growth and condition of Sepia officinalis were evaluated in terms
      of individual growth using different morphometric and biochemical parameters. A
      casein supplemented surimi diet produced significant growth (instantaneous growth
      rate 0.4-0.8% body weight). The digestive gland-to-body weight ratio increased
      and the cuttlebone-to-body weight ratio decreased significantly in relation to
      instantaneous growth rate. The RNA content of mantle muscle increased
      significantly, while the DNA content of mantle muscle did not change in relation
      to instantaneous growth rate. Mantle muscle protein content was depleted in
      cuttlefish with instantaneous growth rate < or = 0. No compensatory food
      consumption, food conversion or growth was observed for cuttlefish fed surimi
      diets after refeeding them with a natural diet (thawed raw shrimp). Digestive
      gland and cuttlebone-to-body weight ratios, and RNA content in mantle muscle
      could be used as short-term indicators of instantaneous growth rate and condition
      of cuttlefish. Mantle muscle protein content could be used as a long-term
      indicator.

PMID- 7828021
TI  - Effects of dehydration, rehydration, and hyperhydration in the lactating and non
      lactating black Moroccan goat.
AB  - The effects of water deprivation, rehydration and hyperhydration were
      investigated in the black Moroccan goat (Capra hircus). Mean daily water intake
      was 46 +/- 5 ml/kg in lactating and 36 +/- 4 ml/kg in non-lactating black
      Moroccan goats, and milk production 21 +/- 1 ml/kg. Mean urine excretion was 8 +/
      2 ml/kg body weight in both groups, and the daily water losses via evaporation
      and feces were estimated at 23 +/- 3 ml/kg during lactation and 28 +/- 4 ml/kg
      during non-lactation. Forty-eight hours of water deprivation caused a body weight
      loss of 9% and 6% in lactating and non-lactating goats, respectively, and a drop
      of 28% in milk production with only a slight decrease in food intake. After
      rehydration, the elevated plasma osmolality as well as Na and total protein
      concentrations returned to basal values within 2-3 hr, indicating a rapid
      absorption of the ingested water, but urine excretion did not increase. After
      hyperhydration (10% of body weight), 46% of the load was excreted by the kidneys
      within 6 hr. In conclusion, black Moroccan goats have a low water turnover, and
      they can retain water upon rehydration but not store excess water after
      hyperhydration.

PMID- 7828022
TI  - Melatonin desensitizing effects on the in vitro responses to MCH, alpha-MSH,
      isoproterenol and melatonin in pigment cells of a fish (S. marmoratus), a toad
      (B. ictericus), a frog (R. pipiens), and a lizard (A. carolinensis), exposed to
      varying photoperiodic regimens.
AB  - Melatonin is a weak dose-independent lightening agonist in fish skin, a moderate
      dose-dependent lightening agonist in toad skin and a potent lightening agent in
      frog and lizard skins (reversing in a dose-dependent manner the darkening caused
      by alpha-melanocyte-stimulating hormone). In frog skins, previous exposure to
      melatonin reduced further lightening actions of the indoleamine, and in toad
      skins, increasing concentrations of melatonin elicited decreasing lightening
      responses, suggesting an autodesensitizing action of the hormone. Various
      concentrations of melatonin diminished the responses to the lightening agonist
      melanin-concentrating hormone (MCH) in fish skins and to the darkening agonists
      alpha-MSH in toad, frog and lizard skins and isoproterenol in frog skins. In
      vitro inhibitory actions of melatonin are mimicked in the absence of the hormone
      in skin preparations from toads kept in continuous darkness for 48 hr. The
      lipophylic nature of the indoleamine associated with the results herein described
      suggests intracellular actions of melatonin on vertebrate pigment cells.

PMID- 7828023
TI  - Free amino acid levels in serum and small intestine during the post-natal
      development of normal and sparse-fur mutant mice.
AB  - Ornithine transcarbamylase (OTC) is a mitochondrial enzyme which catalyzes the
      conversion of ornithine into citrulline. In sparse-fur (spf) mutant mice, in
      which both hepatic and small intestinal OTC are deficient, only small amounts of
      citrulline are released into the blood. To evaluate the fate of ornithine as well
      as the levels of substrates and products of these metabolic pathways in normal
      and OTC-deficient mice, we measured the concentration of free amino acids in
      small intestinal mucosa and serum during post-natal development. In control
      animals, ornithine, alanine and citrulline concentrations in intestinal mucosa
      increased as a function of age, while glutamine, leucine, valine and methionine
      levels decreased around the weaning period. In contrast, the serum concentration
      of these amino acids remained fairly constant. Major changes were observed in spf
      mice: the ornithine level remained low in intestinal tissue, citrulline
      concentration was significantly decreased in both intestinal tissue and blood,
      circulating levels of arginine and essential amino acids were drastically reduced
      in sucklings while plasma glutamine increased after weaning. These data confirm
      the validity of spf mice as a model for the study of nutritional requirements in
      OTC-deficient animals.

PMID- 7828024
TI  - Functional properties of the hemoglobin from the South American snake
      Mastigodryas bifossatus.
AB  - The hemolysate of Mastigodryas bifossatus shows two major hemoglobins with very
      close isoelectric points, and four different globin chains. The stripped
      hemolysate exhibits a low alkaline Bohr effect (delta log P50/delta pH = -0.30
      between pH 7 and 8) and a decrease of the co-operativity from 2.3 to unity when
      the pH increases from 6.15 to 8.5. In the presence of ATP, large changes in the
      oxygen affinity and co-operativity are observed. The Bohr effect rises to -0.46
      and the n50 values stay at around 3 in the pH range 6-9. An increase in
      temperature induces a large decrease in the oxygen affinity for the stripped
      hemolysate. In the pH range between 7.5 and 8.5, the values of delta H in kcal/M
      are around 10 fold larger for the stripped protein than for the protein in the
      presence of ATP. Measurements of rapid kinetics of oxygen dissociation and carbon
      monoxide binding reflect the ATP sensitivity observed in equilibrium experiments.

PMID- 7828025
TI  - Detection and localization of gonadotrophin-releasing hormone (GnRH)-like
      material in the frog, Rana esculenta, ovary.
AB  - GnRH-like material has been identified using HPLC followed by RIA in the ovary of
      Rana esculenta. During the reproductive cycle three immunoreactive GnRH peaks
      were eluted. One of them coeluted with s-GnRH, the other two forms between GnRH
      and cII-GnRH. During the recovery phase s-GnRH immunoreactivity disappears. By
      immunocytochemistry, cII-GnRH immunostaining was localized to granulosa cells
      while s-GnRH was present in the perinuclear zone of the oocytes.

PMID- 7828026
TI  - Titin-related proteins in invertebrate muscles.
AB  - The localization of filaments connecting the Z-line and the A-band in insect
      flight muscles and the identification of very large proteins as their components
      is reviewed. The characterization of twitchin in the obliquely striated muscles
      of Caenorhabditis elegans is reported and the deductions made from its amino acid
      sequence are considered. The characterization of mini-titins in obliquely
      striated molluscan muscles is compared. The identification of projectin in the
      muscles of Drosophila melanogaster by anti-twitchin-antibodies, its sequence
      analysis and the characterization of mini-titins in arthropod and mollusc fast
      striated muscles are summarized. The possible biological functions of the
      different proteins in various invertebrate muscles are discussed.

PMID- 7828027
TI  - Egg chorion tanning in Aedes aegypti mosquito.
AB  - The biochemical pathway of egg chorion tanning in the mosquito, Aedes aegypti, is
      described and compared with chorion protein crosslinking in Drosophila and
      silkmoths and the biochemical pathways of cuticular tanning in insects. Phenol
      oxidase, dopa decarboxylase and tyrosine are critical components involved in egg
      chorion tanning in A. aegypti. Tanning of the mosquito egg chorion is initiated
      following activation of phenol oxidase, which then catalyzes the hydroxylation of
      tyrosine to dopa and further oxidizes dopa and dopamine to their respective o
      quinones. Because intramolecular cyclization is much slower in dopaminequinone
      than dopaquinone, the chance to react with external nucleophiles to participate
      in protein crosslinking reactions also is much greater in dopaminequinone than
      dopaquinone. This might partly explain the necessity for the involvement of dopa
      decarboxylase in mosquito chorion tanning. Intramolecular cyclization of
      dopaquinone and dopaminequinone to form dopachrome and dopaminechrome,
      respectively, the structural rearrangement of these aminochromes to produce 5,6
      dihydroxyindole, and the subsequent oxidation of 5,6-dihydroxyindole by phenol
      oxidase also lead to melanin formation during egg chorion tanning.

PMID- 7828028
TI  - Changes in mammary uptake of free fatty acids, triglyceride, cholesterol and
      phospholipid in relation to milk synthesis during lactation in goats.
AB  - Uptake of free fatty acids (FFA), triglycerides (TG), cholesterol (CHOL) and
      phospholipids (PL) was measured in both mammary glands of dairy goats during
      lactation. Arterial concentrations of TG, CHOL and PL as well as arterio-venous
      difference (AV) and extraction rate (E) for TG were highest in goats with the
      highest dietary feed intake. AV were linearly related to arterial concentrations
      for the four lipid classes, and arterial concentrations of CHOL were linearly
      related to output of lactose, protein and fat in milk. Arterial supply, and not
      mammary synthetic activity, is the main determinant of mammary FFA, TG and CHOL
      uptake.

PMID- 7828029
TI  - Glycogen depletion according to muscle and fibre types in response to dyadic
      encounters in pigs (Sus scrofa domesticus)--relationships with plasma epinephrine
      and aggressive behaviour.
AB  - Changes in glycogen content according to fibre type were assessed in a
      predominantly white (Longissimus) and a predominantly red (Semispinalis) pig
      muscle, in response to dyadic encounters involving aggressive interactions.
      Tested animals showed significantly lower glycogen levels than the control in the
      Semispinalis, but not in the Longissimus muscle. Histological treatment of muscle
      serial cuts followed by computerized image analysis showed that the observed
      decrease in muscle Semispinalis glycogen level occurred only in fast-twitch
      fibres. Total glycogen and glycogen contents in fast-twitch fibres of the
      Semispinalis muscle were closely and negatively related to aggressive behaviour,
      but not with plasma epinephrine levels during and at the end of the encounters.
      The present results provide indirect evidences suggesting a major influence of
      fighting-induced physical activity on muscle glycogen depletion in response to
      aggressive interactions in pigs.

PMID- 7828030
TI  - Plasma melatonin concentration in neonatal northern elephant seals, Mirounga
      angustirostris.
AB  - The development of pineal function in northern elephant seals was examined in an
      attempt to understand the physiological basis for previously observed high
      daytime levels of melatonin in neonatal southern elephant seals. Pineal glands
      from four northern elephant seal pups, estimated age less than 1 week, weighted
      3.0 +/- 0.80 g, which was significantly less than that previously found in
      southern elephant seals (4.6 +/- 0.35 g). Midday concentrations of plasma
      melatonin in pups averaged more than 3000 pmol/l in the first 5 days post-partum,
      but declined rapidly to less than 400 pmol/l after day 9. Daytime melatonin
      levels in northern elephant seals tended to be lower than in southern elephant
      seals, although they were very high compared with other species. A circadian
      cycle of plasma melatonin concentration was observed in newborn northern elephant
      seals, with levels of 3000-5000 pmol/l during the day, rising to more than 10,000
      pmol/l late in the dark phase. Soon after weaning at 4 weeks of age, daytime and
      night-time levels were in the range 60-100 pmol/l and 100-400 pmol/l,
      respectively. When approximately 10 weeks old, most samples were in the range 100
      400 pmol/l with no discernible difference between day and night levels. The
      results do not support the hypothesis that the pineal gland is involved in
      thermogenesis in new-born southern elephant seals. Instead, the very active
      pineal gland may contribute to energy conservation, by lowering body temperature,
      particularly at night. As physical insulation is acquired by the deposition of
      blubber, the mechanism is not required and melatonin falls to adult levels.

PMID- 7828031
TI  - Pancreas disease in Atlantic salmon (Salmo salar) and vitamin E supplementation.
AB  - A study was instigated to investigate the histopathological and clinical
      pathological lesions associated with a naturally occurring pancreas disease (PD)
      outbreak in farmed Atlantic salmon. An attempt was made to reduce the severity of
      PD and associated lesions by altering the antioxidative and peroxidative
      substrates in the diets. The results do not support the hypothesis that PD leads
      to a vitamin E deficiency which induces a myopathy. PD was not associated with a
      reduction in tissue vitamin E concentrations. Despite high tissue vitamin E
      concentrations, pancreatic lesions and cardiac and skeletal myopathy occurred
      almost simultaneously. Severe myopathy appeared to be associated with high
      mortality. Dietary vitamin E concentrations > 500 mg/kg did not increase plasma
      and muscle vitamin E concentrations, which appear to be saturated. Liver
      concentrations were also high. However, differing concentrations of dietary
      vitamin E and fat were associated with differing mortality rates.

PMID- 7828032
TI  - Soybean trypsin inhibitors in diets for Atlantic salmon (Salmo salar, L): effects
      on nutrient digestibilities and trypsin in pyloric caeca homogenate and
      intestinal content.
AB  - Atlantic salmon (Salmo salar, L), 180 g, were fed diets containing a crude
      trypsin inhibitor from soybean at five levels. The five levels resulted in
      trypsin inhibitor activities (TIA) corresponding to an inclusion of 0 to about
      100% commercial soybean meal. Digestibility of protein and fat, weight gain and
      trypsin activity in intestinal content were significantly reduced with increasing
      dietary TIA. The response curves for nutrient digestibility and growth indicated
      that the Atlantic salmon were able to compensate for a certain TIA, equivalent to
      about 5 mg bovine trypsin inhibited per g feed. This compensation seemed to be
      due to increased trypsin secretion as suggested by the values for total content
      of trypsin in the pyloric caeca homogenate. At the highest level of TIA, the
      pancreatic capacity of trypsin synthesis seemed to be exhausted.

PMID- 7828033
TI  - Comparative study of hemolymph phenoloxidase activity in Aedes aegypti and
      Anopheles quadrimaculatus and its role in encapsulation of Brugia malayi
      microfilariae.
AB  - Hemolymph phenoloxidase activity of sugar-fed and blood-fed females of Anopheles
      quadrimaculatus and Aedes aegypti showed similar characteristics. Phenoloxidase
      was present as an inactive proenzyme in both mosquito species and was partially
      activated during collection of the hemolymph. In both mosquito species,
      phenoloxidase activity was modulated by different buffers and activated
      phenoloxidase did not need Ca2+. Enzymatic activity was higher in the hemocytes
      than in the plasma in both mosquito species. Trypsin, laminarin, and blood
      feeding on uninfected and Brugia malayi-infected jirds enhanced hemolymph
      phenoloxidase activity in both mosquito species. The appearance of hemolymph
      phenoloxidase activity was inhibited by p-nitrophenyl p'-guanidinobenzoate HCl,
      soybean trypsin inhibitor, ethylenediaminetetraacetic acid, diethyldithiocarbamic
      acid, saturated 1-phenyl-2-thiourea and reduced glutathione, but not by
      benzamidine in A. quadrimaculatus. The appearance of hemolymph phenoloxidase
      activity was inhibited by benzamidine, diethyldithiocarbamic acid, saturated 1
      phenyl-2-thiourea, reduced glutathione, p-nitrophenyl p'-guanidinobenzoate and
      soybean trypsin inhibitor, but not by ethylenediamine-tetraacetic acid in A.
      aegypti. It is suggested that in both mosquito species, blood-feeding and
      migration of sheathed microfilariae in the homocoel activated the
      prophenoloxidase in the hemolymph and caused the encapsulation and melanization
      of microfilarial sheaths and microfilariae of B. malayi.

PMID- 7828034
TI  - Potassium activation of Na(+)-dependent leucine transport in brush-border
      membrane vesicles from rat jejunum.
AB  - Na(+)-dependent leucine uptake was greater in potassium loaded brush-border
      membrane vesicles compared with controls. This effect was not mediated by an
      electrical potential difference, since it was still present in voltage-clamped
      conditions. Inhibition experiments indicate the same Na(+)-dependent leucine
      transport activity in the presence or in the absence of potassium. The affinity
      of sodium for the cotransporter was identical at 10 or 100 mM potassium. Leucine
      kinetics at different potassium concentrations showed a maximum 2.4-fold increase
      in Vmax, while Km was unaffected. The secondary plots of the kinetic results were
      not linear. This kinetic behavior suggests that K+ acts as a non-essential
      activator of Na(+)-dependent leucine cotransport. A charge compensation of sodium
      leucine influx is most probably a component of the potassium effect in the
      presence of valinomycin.

PMID- 7828035
TI  - Intracellular Na+ and K+ shifts induced by contractile activities of rat skeletal
      muscles.
AB  - The effects of direct and indirect electrical stimulation on intracellular
      potassium and sodium contents ([K]i and [Na]i, respectively) in rat soleus muscle
      (SOL) and extensor digitorum longus muscle (EDL) were investigated under in vivo
      conditions. The changes of [K]i and [Na]i contents in both muscles which were
      stimulated indirectly reached respective values at 30 min or 1 hr after the
      beginning of stimulation, whereas those of EDL stimulated with 60 Hz changed
      gradually through 2 hr stimulation. The shifts of [K]i and [Na]i in EDL occurred
      during the twitch contraction at considerably lower frequency stimulation (0.5-10
      Hz), whereas those in SOL were observed during the tetanus contraction at high
      frequency stimulation (10-40 Hz). The difference of change in cationic shifts
      between EDL and SOL under low frequency stimulation was reduced by ouabain
      treatment, though the difference was still significant. When the muscles were
      indirectly stimulated 6000 times at 1, 5, 10 and 20 Hz, the cationic shifts in
      EDL were greater than those in SOL, extending over all frequencies. It was
      concluded that such a difference in ionic shift between contracting EDL and SOL
      may be primarily due to the difference in unidirectional ionic fluxes per
      stimulation and, secondly, to the difference in Na(+)-K+ pump activity.

PMID- 7828036
TI  - Potassium currents in cultured cells of the rat retinal pigment epithelium.
AB  - Whole-cell currents were investigated in cultured rat retinal pigment epithelial
      (RPE) cells. Two voltage-dependent conductances were discriminated. First, at
      potentials more positive than -30 mV, a time-dependent outward current was
      activated. Inhibition by Ba2+ (10 mM) and 4-aminopyridine (10 mM) indicated that
      this current was carried by potassium ions. This current showed no inactivation
      during 5 sec depolarizations. Second, an inward current, sensitive to Ba2+ (10
      mM) and 4-aminopyridine (10 mM), was activated at potentials more negative than 
      70 mV. Under extra- and intracellular potassium-free conditions, both currents
      disappeared. In summary, cultured rat RPE cells expressed one potassium
      conductance similar to the delayed rectifier and one similar to the inward
      rectifier. The delayed rectifier expressed characteristics comparable with those
      known in mammalian species and different from those in non-mammalian species.

PMID- 7828037
TI  - Postprandial increase in the duodenal pH and the effect of intravenous secretin
      injection on ionic compositions of duodenal fluid and plasma in sheep.
AB  - Testing five castrated male sheep with a pH-electrode inserted into the duodenal
      digesta through a T-shaped cannula, we found that the pH of the duodenal digesta
      was significantly increased from 3.11 +/- 0.11 to 3.47 +/- 0.09 after a meal.
      Secretin (2.5 CHR U/kg) was intravenously injected to mimic the duodenal pH
      increase. The administration significantly increased the duodenal digesta pH from
      3.32 +/- 0.18 to 4.85 +/- 0.61, which was accompanied by an increase in sodium
      concentration, but by a decrease in potassium and chloride concentrations. It
      also significantly decreased the arterial blood pH from 7.543 +/- 0.002 to 7.515
      +/- 0.008, which was accompanied by a reduced plasma HCO3- concentration. From
      these results, we conclude that in sheep, feeding increases the duodenal digesta
      pH, and the postprandial pH increase in the duodenal fluid would be due to the
      raised HCO3- secretion from the gastrointestinal tract.

PMID- 7828038
TI  - A pain assessment tool for all children.

PMID- 7828039
TI  - Endotracheal suctioning and the neonate.

PMID- 7828040
TI  - Formation of a neonatal transport team.

PMID- 7828041
TI  - Meningitis in childhood.

PMID- 7828042
TI  - Clinical supervision.

PMID- 7828043
TI  - Measurement of functional ability in patients with coronary artery disease.
AB  - The purpose of this study was to examine measures of functional ability in a
      group (n = 60) of cardiac patients undergoing treadmill exercise tests.
      Functional ability was defined as the degree to which the individual is able to
      perform physical activity in the absence of symptoms. Instruments used were the
      Modified Harvard Alumni Scale (MHAS), the Symptom Scale (SS) comprised of the
      following subscales: angina (AS), shortness of breath (SOBS), and fatigue (FS);
      the overall Health Rating Index (OHRI); and the Goldman Specific Activity Scale
      (SAS). Concurrent validity was supported by the fact that the instruments were
      correlated with metabolic equivalents achieved on the treadmill. Correlations
      were: MHAS (r = .34, P < .01), SS (r = .67, p < .01), AS (r = .54, p < .01), SOBS
      (r = -.41, p < .05), FS (r = -.56, P < .001) and the OHRI (r = .45, p < .001).
      Reliability was determined using Cronbachs, alpha and were: SS = .92, AS = .87,
      SOBS = .86, FS = .85 and OHRI = .88. Findings support the need for testing and
      evaluation of instruments measuring functional ability in diverse cardiovascular
      populations.

PMID- 7828044
TI  - A quantitative survey to measure energy expenditure in midlife women.
AB  - The Taylor Leisure Time Physical Activity Questionnaire and the Tecumseh
      Occupational Physical Activity Questionnaire were modified to measure energy
      expenditure in midlife women. A three-dimensional measure of female physical
      activity resulted which reflected leisure, occupational, and household
      activities. Total daily energy expenditure for the specific activities was
      calculated using established metabolic units and reported time spent performing
      the activities. Test-retest reliability was evaluated at two weeks for 15% (n =
      59) of the sample of 375 midlife women. There was high agreement on participation
      in the various activities, but low agreement on the time spent doing the
      activities. Cardiorespiratory fitness, established with a Monarch bicycle
      ergometer, was used to test the validity of the energy expenditure measure.
      Correlations were significant between cardiorespiratory fitness and both leisure
      activity and household activity, but not between cardiorespiratory fitness and
      occupational activity.

PMID- 7828045
TI  - Measuring well to study well.

PMID- 7828046
TI  - Measurement of mealtime interactions among persons with dementing disorders.
AB  - Difficulty in eating and refusal to eat are common problems for severely demented
      persons. Feeding can be one of the most frustrating and complex daily tasks
      performed by caregivers of demented elders in institutional settings. This paper
      describes the development of a new method for measuring caregiver-elder feeding
      activities and interactions--the Feeding Traceline Technique (FTLT). The FTLT,
      which involves both the transcription of videotape recorded data and the coding
      of data for computer input, is designed to account for all mealtime behaviors of
      both feeders and elders, to account for the cyclic and repetitive nature of
      eating and to permit quantification of complex interactions between feeders and
      institutionalized residents. Data describing the reliability and validity of the
      method are presented. Issues discussed relate to the units of analysis, the time
      and energy expenditure of the method in comparison to the yield of information,
      and the effect of videotaping on measurement.

PMID- 7828047
TI  - Development of the Stimulus Intensity Modulation Scale.
AB  - The purpose of this study was to theoretically base, develop, and test items for
      the Stimulus Intensity Modulation Scale (SIMS) which was intended for use in
      healthy as well as ill populations. According to stimulus intensity modulation
      theory, persons vary in their need for stimuli, depending on their nervous
      system's ability to modulate sensory stimuli. Content validity was established
      for the SIMS and a principle component extraction with varimax rotation resulted
      in a three-factor solution supporting the theoretical factors of pain tolerance,
      attention and habituation. Item analysis resulted in a final scale of 27 items.
      An internal consistency of .81 was achieved for the overall SIMS. Respective
      subscale coefficients of .82, .74, and .63 were obtained. Test-retest
      coefficients of .92, .83, .79 and .95 for the total scale and its subscales,
      respectively, were obtained over a 1-month period. Discriminant validity and
      freedom from socially desirable response bias was also accomplished.

PMID- 7828048
TI  - Childbirth and the measurement of fatigue.
AB  - Fatigue during labor concerns women and nurses alike, yet few studies have
      directly measured fatigue during childbirth. Many issues and difficulties with
      the conceptualization and measurement of fatigue have been raised because of the
      multidimensionality of the concept. Fatigue was conceptualized as including
      subjective, cognitive, and physical dimensions, and was therefore operationalized
      using multiple methods. In the two studies described, fatigue was measured using
      the Modified Fatigue Symptom Checklist (MFSC), the Pearson-Byars Feeling
      Checklist (PBFC), Visual Analogue Scales (VAS), the Digit Span Subtest of the
      Wechsler Intelligence Test (revised R), and a hand held bulb dynamometer. These
      studies support the reliability and validity of the measures used to quantify
      fatigue during labor. These findings support the operationalization of fatigue as
      a multidimensional concept.

PMID- 7828049
TI  - Measuring managerial motivation: the Power Management Inventory.
AB  - Psychometric properties for Part I of the Power Management Inventory (Hawker &
      Hall, 1981) are presented following validation of the instrument with samples of
      nurse managers (N = 54) and executives (N = 92). The content validity indices
      were .85 for management issues (item stems), .65 for Personalized Power (PP), .75
      for Socialized Power (SP), and .70 for Affiliative Motive (AM) scales. Internal
      consistency reliabilities were acceptable (.63 to .87). Test-Retest correlations
      (n = 19 managers) ranged from .74 to .85. Correlation of nurse manager (n = 50)
      scores with subordinate scores of managers were significant (p < .05) for PP (r =
      .32) and AM (r = .29). Correlation of nurse executive (n = 59) scores with chief
      executive officer scores of executives were significant for PP (r = .32, p < .01)
      and AM (r = .25, p < .05). Mean scores of PP, SP and AM failed to profile the
      motive pattern for "successful" managers. About 29% of the managers and 39% of
      the executives were categorized as having no power motive preference. Use of the
      PMI for career counseling/decisions in nursing is not recommended, however, its
      use as an organizational development tool is endorsed.

PMID- 7828050
TI  - Circadian rhythms and nursing research: methodological considerations.
AB  - The role circadian rhythms play in mental health, sleep, human development and
      aging, pharmacologic efficacy, immune function, and cardiovascular health makes
      them a natural focus of nursing research. Integration of chronobiologic concepts
      into nursing care demands sound empirical support. Nevertheless, issues such as
      detection of linear trends, the fit of circadian data to a cosinor model and
      circular distributions, add complexity to the collection, analysis and
      interpretation of circadian rhythm data. The purpose of this paper is to convey
      an informed understanding of ways in which to deal with this intricate assembly
      of issues.

PMID- 7828051
TI  - Moving into a new era.

PMID- 7828052
TI  - Professional codes: an exercise in tokenism?
AB  - The paper questions the effectiveness of the United Kingdom Central Council's
      (UKCC's) Code of Professional Conduct upon the moral climate of nursing. It
      challenges the claim that the empowerment of nurses is significantly enhanced by
      the Code or that it necessarily makes them more accountable for their practice.
      The position is taken that the Code, in the absence of an effective support
      network for whistle-blowers, places an unreasonable burden upon nurses in its
      exhortations to report unprofessional conduct. The paper acknowledges the need to
      retain the Code, but with more modest claims being made concerning its empowering
      qualities. It is argued that unless more attention is focused on ways to support
      potential whistle-blowers, the Code will come to be seen as an irrelevance.

PMID- 7828053
TI  - Professional nurses should have their own ethics: the current status of nursing
      ethics in the Dutch curriculum.
AB  - Should nurses have their own ethics to match specific problems met in their daily
      routines? How do nurses act in a society that is changing from a 'monocultural'
      to an 'intercultural' structure? What are the ethical consequences of these
      changes for their many tasks? How can the ethical aspects be taught to nurses?
      This article describes the current status of nursing ethics in the curriculum
      taught in schools of higher education for nurses in The Netherlands. Aspects of
      the debate on nursing ethics are outlined and ideas about its future as a subject
      and discipline in nurse education are offered.

PMID- 7828054
TI  - Building bridges: teaching ward-based ethics.
AB  - Ethics has traditionally been taught in the 'ivory towers' of academia. Recent
      developments and reforms in nurse education have given ethics a prominent
      position in most curricula. However, the vast majority of ethics teaching
      continues to take place in academic departments. This approach fuels the
      practitioner's views that nursing is a pragmatic activity whilst ethics is a
      cognitive endeavour; such perspectives entrench ethics firmly in the traditional
      gap between theory and practice. The focus of this paper presents an argument
      that the teaching of ethics must be versed in clinical reality if bridges are
      ever to be built and the theory-practice gap crossed.

PMID- 7828055
TI  - Mixing the genders, an ethical dilemma: how nursing theory has dealt with
      sexuality and gender.
AB  - As nursing moves towards a holistic approach to care, its publications on
      sexuality have proliferated. 'Sexuality' and 'Gender' are concepts which are
      extremely difficult to define. While sex refers to the physical differences of
      the body, gender concerns the psychological and sociocultural differences between
      females and males. This distinction between sex and gender is fundamental, since
      many differences between females and males are not biological in origin. And,
      when a person's gender and sex fall together in accordance with social norms, it
      may not necessarily be a similar correlation for every individual. The nature of
      these similarities is essentially threefold. First, Thomas, Savage and Webb
      accept that there should be a nursing definition of sexuality. In different ways
      they acknowledge and refer to it as an integral part of a person's being and self
      concept. Secondly, the authors underline some of the complexities and
      difficulties nurses have defining and dealing with it in professional
      relationships as well as on the level of self reflection, knowledge, attitudes
      and beliefs. Thirdly, all three surveys show why such difficulties prevail, and
      go on to make suggestions for change in nursing interventions and training. This
      article summarizes these contributions and discusses the ethical problems which
      nurses face in dealing with the sexuality of their patients.

PMID- 7828056
TI  - Forcible caesarean: a new direction in British maternity care? Thoughts on the
      case of Mrs S.

PMID- 7828057
TI  - An International Code of Ethics for midwives. International Confederation of
      Midwives.

PMID- 7828058
TI  - Ethical guidelines for nursing--Denmark. Danish Nurses' Organization.

PMID- 7828059
TI  - Amendment No. 62 to the Education Bill, third reading, House of Lords, 6 July
      1993.

PMID- 7828060
TI  - Identification of a set of frequent decanucleotides in plants and in animals.
AB  - We studied the frequency distribution of 1,048,576 oligonucleotides 10 bp long in
      a sample of 1.961 Mbase of genes from plants, made of 635 sequences extracted
      from GenBank 71.0, with the aim of detecting transcription control signals. Among
      all decamers, 3255, or 0.3%, had a frequency 10 times higher than the mean and
      were subjected to further statistical analysis. For each of the 3255 decamers
      (parents), we counted the individual frequencies of the 30 decamers (progeny)
      differing from the parent by one base mutation, and 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
      3255 decamers > 10 times frequent than average, 432 had a chi-square ratio > 1.9.
      In this residual set, which corresponds to < 0.04 per cent of all possible
      decamers, only 15 known eukaryotic transcription control elements were found; on
      the other hand, it included 29 decanucleotides that matched with decanucleotides
      of a set of Drosophila, 24 with a set from mammals, 13 with a set from yeast and
      four with a set of viruses--all sets identified with the statistical procedures
      here described. These decanucloetides are highly repetitive and seem to be
      present throughout all higher organisms, whereas they are uncommon in mammalian
      viruses.

PMID- 7828061
TI  - Rapid numerical integration algorithm for finding the equilibrium state of a
      system of coupled binding reactions.
AB  - We have adapted a simple method of numerical integration to predict the
      equilibrium state of a population of components undergoing reversible association
      according to the Law of Mass Action. Its particular application is to populations
      of protein molecules in aqueous solution. The method is based on Euler
      integration but employs an adaptive step size: the time increment being reduced
      if it would make the concentration of any component negative and increased while
      the concentration of any component changes at greater than a specified rate.
      Parameters of the algorithm have been optimized empirically using a model set of
      binding equilibria with dissociation constants ranging from 10(-5) M to 10(-9) M.
      The method obtains the solution to a set of binding equilibria more rapidly than
      the conventional initial value methods (simple Euler, 4th order Runge-Kutta and
      variable-step Runge-Kutta methods were tested) for the same accuracy. A computer
      code in standard C is presented.

PMID- 7828062
TI  - BIOESTIM: software for automatic design of estimators in bioprocess engineering.
AB  - This paper describes BIOESTIM, a software package devoted to on-line estimation
      in bioprocess engineering. BIOESTIM enables bioengineers automatically to design
      state and parameter estimators from a minimal knowledge of the process kinetics.
      Such estimators allow development of software sensors capable of coping with the
      lack of reliable instrumentation suited to real-time monitoring. The estimator
      building procedure through BIOESTIM starts up from a dynamical material balance
      model of the bioprocess. This model, supplied by the user, is next completed by
      other information with no requirement for numerical values: the user has only to
      specify available measurements, coupled reactions and the known yield
      coefficients. On the base of this knowledge, BIOESTIM proceeds to symbolic
      algebraic manipulations on the model in order to study estimation possibilities
      and check identifiability of yield coefficients. When the design of an estimator
      is possible, the corresponding equations are automatically generated. Moreover,
      these estimators are stored in a user-specified file which is automatically
      interfaced with a specialized simulation software including data treatment and
      numerical integration packages. Thus, the user can simulate the estimator
      performances under various operational conditions using available experimental
      measurements. A typical example dealing with microbial growth and biosynthesis
      reactions is given in order to illustrate the main functional capabilities of
      BIOESTIM. BIOESTIM has been designed and written in a modular fashion. The module
      dealing with estimators design makes use of symbolic computation; it is written
      in Mathematica and runs on every computer on which this language is available.

PMID- 7828063
TI  - An algorithm to determine protein sequence alignment by utilizing data obtained
      from a peptide mixture and individual peptides.
AB  - With the aim of limiting peptide purification steps and unambiguously
      ascertaining protein sequences, we have designed and implemented on a personal
      computer an algorithm to determine sequence alignment by utilizing data obtained
      from automatic Edman degradation performed on a single peptide mixture and
      individual peptides. The protein under study is digested by two different
      hydrolysis methods and fragments are just isolated from one mixture and
      sequenced, while the second mixture is submitted unfractionated to sequence
      analysis. The algorithm provides for the exact alignment of the individual
      peptides using the mixture data for the overlapping. We report an example of
      application of this approach by utilizing experimental data obtained from a
      protein of known sequence.

PMID- 7828064
TI  - An Excel spreadsheet computer program combining algorithms for prediction of
      protein structural characteristics.
AB  - A program running on personal computers (either Apple Macintosh or PC, using
      Excel worksheets) for the prediction of some protein structural characteristics
      is reported. The program runs according to the Chou and Fasman algorithm, with
      some modifications, for secondary structure prediction. The program also
      incorporates several complementary analyses for secondary structure prediction to
      help the user in the decision-making process: rules for amino acid preferences in
      the N-cap and C-cap of alpha-helices; prediction of the protein structural class
      and search of sequential motifs related to secondary structure. Additional
      algorithms performed by the program are: prediction of domain boundaries,
      prediction of loops, prediction of the state of cysteines (reduced or in
      disulfide bridge), hydropathy profiles according to Kyte and Doolittle, Hoop and
      Woods, and flexibility plot according to Karplus and Schulz.

PMID- 7828065
TI  - A set of Alu-free frequent decamers from mammalian genomes enriched in
      transcription factor signals.
AB  - We have recently reported that the statistical analysis of the frequency
      distribution of short oligonucleotides within mammalian and viral genomes allows
      the production of sets of DNA sequences enriched in signals for transcription
      factors. Such statistical approaches could facilitate the identification of new
      promoter regions playing a role in the transcriptional regulation of gene
      expression. In the case of mammalian oligonucleotides, we found that the
      published set of frequent decamers enriched in transcriptional motifs is not
      suitable for studies on genes of Homo sapiens and evolutionarily related genomes,
      because it contains decameric sequences belonging to genomic repeats. We report
      here that most of the decameric sequences of DNA repeats belong to Alu repeats.
      Accordingly, we produced a subset of Alu-free frequent decamers. In addition, we
      eliminated from the subset of Alu-free frequent decamers those that are
      frequently present within other common human repeats, including (GT)n, (AT)n,
      (CA)n, (ATT)n, (CAA)n and (GTT)n. The Alu-free (repeats-free) subset of frequent
      mammalian decamers is enriched in signals for transcription factors and allows
      the identification of putative signals in genes, such as those coding for
      plasminogen activator, adenosine deaminase and p53, that contain a large number
      of Alu-like repeats interspersed within our genomic sequences. The newly
      generated compilation of frequent decamers described here might be used to locate
      genomic regions playing functional roles in the expression of genes of Homo
      sapiens and related primates.

PMID- 7828066
TI  - On an efficient parallelization of exhaustive sequence comparison algorithms on
      message passing architectures.
AB  - We present a new parallel computing approach to the case of exhaustive sequential
      sequence comparison algorithms on message-passing architectures. In this context
      a modification of guided self-scheduling as well as efficient buffering
      strategies are presented. We discuss two specific implementations, one on the
      Paramid parallel computer, and the other on a cluster of workstations running
      PVM. In both cases the parallel performance is higher than with any other method
      presented so far. The code is public domain and can be obtained by anonymous ftp
      at ftp.cnb.uam.es.

PMID- 7828067
TI  - Maximum likelihood estimation of quantitative trait loci parameters with the aid
      of genetic markers using a standard statistical package.
AB  - Consistent parameter estimates of quantitative trait loci linked to genetic
      markers can be derived by maximum likelihood methodology. For many experimental
      designs of interest, parameter estimates and their standard errors can be
      obtained by program LE of BMDP, which uses the Newton-Raphson method of
      iteration. Program LE was tested on data simulated for a backcross between two
      inbred lines. A single quantitative trait locus linked to either one or two
      genetic markers was simulated. Convergence was rapid, and computing and
      programming time were insignificant. All parameter estimates were within the
      expected bounds. Many different designs can be readily analyzed.

PMID- 7828068
TI  - A new concept of sequence data distribution on wide area networks.
AB  - Accepted concepts in distributed applications design have been applied in the
      development of a network-based system for the synchronization of remote sequence
      database access sites by an incremental update mechanism. Computer hardware
      requirements, network bandwidth, and stability considerations make centralized
      access to essential computerized resources undesirable. A network model has been
      developed to distribute access over a collection of remotely situated computer
      centers. The formally independent database-access nodes join to form a
      heterogeneous, long distance, co-operating network that can compensate for the
      deficiencies of unstable network links thereby ensuring uninterrupted access to
      the resource. In order to guarantee consistency among these nodes, several
      distributed transaction protocols have been investigated; based on these results,
      a prototype system has been implemented. A layered software architecture makes
      the distributed transaction protocol transparent to the individual database
      system and the underlying network. Individual components of this network
      communicate by means of Remote Procedure Calls (RPCs). A prototype software
      system operates to synchronize up to data copies of the PIR-International Protein
      Sequence Database (Barker et al., 1993) at a number of different sites using the
      public Internet as the transport vehicle.

PMID- 7828069
TI  - A consensus procedure for predicting the location of alpha-helical transmembrane
      segments in proteins.
AB  - To aid in the development of three-dimensional models of membrane-bound proteins,
      a consensus procedure for predicting alpha-helical transmembrane segments from
      amino acid sequence is presented. The algorithm combines the results of six
      individual prediction methods and some basic properties of membrane-spanning
      helices to obtain a final consensus prediction. Comparison with experiment and
      several other recently developed methods shows that the consensus procedure
      performs quite well in comparison to other recent methods. A FORTRAN program has
      been developed which takes an input file containing an amino acid sequence in one
      letter code and outputs a list of the alpha-helical transmembrane segments
      predicted by the consensus algorithm.

PMID- 7828070
TI  - VISA: Visual Sequence Analysis for the comparison of multiple amino acid
      sequences.
AB  - VISA (VIsual Sequence Analysis) is a software package that displays global
      similarities within a set of related protein sequences. The program identifies
      amino acid patterns that are common to many members of the set of sequences and
      displays them as a series of histograms. Individual peaks on the display can be
      assigned a color and analogous peaks in the other sequences are then
      automatically marked in the same color. This can be repeated for each significant
      peak and leads to a display in which major matching segments of multiple amino
      acid sequences appear as dominant peaks of the histograms with matching colors.
      These peaks usually correspond to the conserved sequence motifs that are
      characteristic of particular proteins. An extensive set of software tools is
      included to help the localization, visualization and analysis of the global
      similarities displayed. VISA provides a graphic overview of the sequence
      similarity that can help to understand the architecture of the protein family and
      can be helpful while designing experiments to probe function.

PMID- 7828071
TI  - PdbMotif--a tool for the automatic identification and display of motifs in
      protein structures.
AB  - A program PdbMotif, which automatically identifies protein motifs in a protein
      data bank file and generates a script file which can be read directly by the
      molecular rendering program RasMol, is described. PdbMotif accepts the standard
      PROSITE pattern syntax and will scan the PROSITE pattern database or a set of
      user defined patterns. Any motifs detected are automatically highlighted in the
      RasMol image.

PMID- 7828072
TI  - Gnome--an Internet-based sequence analysis tool.
AB  - Gnome (GenomeNet Open Mail-service Environment) is a sequence analysis tool that
      enables an end-user to make use of several Internet- (mainly e-mail) based
      services with an easy-to-use graphical user interface. Users can conduct homology
      and motif searches, and database-entry retrieval against the latest databases by
      emitting search requests to and receiving their results form a search-server by e
      mail. The search results are viewed and managed efficiently with this system. The
      Macintosh and X (Motif) versions of the Gnome client and the UNIX version of the
      Gnome server are available to academic users free of charge.

PMID- 7828073
TI  - Navigating the Brookhaven Protein Data Bank.
AB  - The Protein Data Bank maintained at Brookhaven National Laboratories has expanded
      to the point where even experienced users have difficulty understanding,
      exploring, and exploiting it. This paper describes a text file, an annotation of
      the Protein Data Bank, which helps users find information on related files and
      structures. The most recent version of this file includes information on
      homologous structures, including both sequence homology and structural homology.
      This file is in ASCII format and is available electronically. It is easy to
      search locally on any type of computer, using an editor or a pattern-matching
      program, such as grep.

PMID- 7828074
TI  - Computing heart rate variability using spectral analysis techniques: HRVUAB, a
      ready-to-use program.
AB  - The application of spectral analysis techniques to study the nervous modulation
      of the vertebrate heart have given interesting results in clinical studies
      although nearly nothing is known in lower vertebrates. A program to compute this
      heart rate variability is described in detail and preliminary results are shown.
      Data is first statistically qualified and fragmented in smaller segments, each
      being further processed through linear trend removal and normalization before the
      application of the Fast Fourier Transform algorithm to estimate the interval
      spectrum. All consecutive periodograms are averaged and the interval spectrum
      plotted and saved.

PMID- 7828075
TI  - TRACTOR, a program to locate subclones in a nucleotide sequence using only one
      sequencing reaction.
AB  - The QuickBasic program TRACTOR is used to locate clones in a known sequence using
      only one sequencing reaction, a method generally known as 'T-tracking'. The
      program can reduce workload at the end stage of a sequencing project using the
      random subcloning strategy.

PMID- 7828076
TI  - GenFrag 2.1: new features for more robust fragment assembly benchmarks.

PMID- 7828077
TI  - TREECON for Windows: a software package for the construction and drawing of
      evolutionary trees for the Microsoft Windows environment.

PMID- 7828078
TI  - Uterine vascular permeability after uterine stimulation to rats differentially
      sensitized for the decidual cell reaction.
AB  - Uterine vascular permeability (VP) was assessed after unilateral intrauterine
      injection of sesame oil to rats given either optimal sensitization for the
      decidual cell reaction or one of several forms of suboptimal sensitization. The
      study was intended to determine the relationship between changes in uterine VP
      and imminent endometrial decidualization. Uterine VP was estimated by the rate at
      which the uterine volume of distribution of i.v. injected 125I-labeled albumin
      approached the uterine extracellular fluid volume (ECFV). When ideal
      sensitization was provided, uterine VP was significantly greater in stimulated
      than nonstimulated horns at 4, 8, 16, and 32 h after stimulation (p < 0.05).
      Maximum VP in stimulated horns occurred at 8 h, with the time for the 125I
      labeled albumin volume to reach half the uterine ECFV (t1/2) estimated to be 30
      min. Different types of sensitization resulted in different levels of uterine VP
      in stimulated and nonstimulated horns, with maximal VP occurring in stimulated
      horns of rats that had previously received optimal sensitization for
      decidualization. We conclude that endometrial decidualization is preceded by
      significant increases in uterine VP and that optimal sensitization promotes an
      optimal VP response.

PMID- 7828079
TI  - Effect of potassium-induced cortical spreading depression on prostaglandin
      induced fever in conscious and urethane-anesthetized rats.
AB  - Potassium-induced cortical spreading depression (CSD) on prostaglandin E1 (PGE1)
      induced fever has been investigated in a dose-responsive experimental design in
      both conscious and urethane-anesthetized adult male Sprague-Dawley rats. While
      CSD in itself had no effect on nonfebrile body temperature even under cold
      ambient conditions, CSD significantly suppressed small but not large fevers
      induced by intracerebroventricular PGE1. The increased oxygen consumption during
      fever was also reduced. We also explored the possible involvement of the
      antipyretic peptide arginine vasopressin, in the CSD-induced suppression of
      fever. Long term castrated rats have significantly reduced ventral septal levels
      of this peptide, yet CSD was effective in suppressing the initial 40 min of PGE1
      fever in these animals. Thus we conclude that increased release of ventral septal
      arginine vasopressin is probably not involved in the action of CSD on fever.

PMID- 7828080
TI  - Relation of glycosylated hemoglobin to in vivo cardiac function in response to
      dobutamine in spontaneously diabetic BB Wor rats.
AB  - The contribution of metabolic control to in vivo myocardial contractile function
      in response to beta 1-adrenergic stimulation was determined in the spontaneously
      diabetic BB Wor rat. The study involved a group of insulin-dependent BB Wor rats
      showing marked variations in metabolic control, assessed by the level of
      glycosylated hemoglobin (gHb). These diabetic BB rats were divided into moderate
      and severe (%gHb > 14), diabetic groups. A group of Wistar rats and diabetes
      resistant BB Wor rats served as controls. In vivo myocardial contractile function
      was measured under basal conditions and after i.v. dobutamine infusions in
      anesthetized rats, using a catheter-tip pressure transducer inserted into the
      left ventricle. No dramatic differences in heart rate with dobutamine stimulation
      were observed between the moderate, severe diabetic, and diabetes-resistant
      groups. However, heart rate was lower in Wistar control rats compared with these
      groups. Systolic left ventricular pressure was depressed in severe diabetic rats
      compared with Wistar controls. In addition, positive dP/dt was significantly less
      in the severe diabetic group at the highest doses of stimulation, whereas
      negative dP/dt was depressed under basal conditions and remained so with
      increasing doses of dobutamine. In the diabetic group maximal systolic left
      ventricular pressure, rate-pressure product, and negative dP/dt responses to
      dobutamine were all inversely correlated with gHb. These results indicate that
      changes in metabolic control of the insulin-dependent BB diabetic rat can
      contribute to a depressed myocardial contractile function.

PMID- 7828081
TI  - Intracellular calcium concentrations during metabolic inhibition in the
      motoneuron cell line NSC-19.
AB  - Changes in the concentrations of intracellular free calcium ([Ca2+]i) and adenine
      nucleotides were determined in response to metabolic inhibitors in the motoneuron
      cell line NSC-19. The NADH dehydrogenase inhibitor amobarbital (Amytal) and the
      mitochondrial uncoupler carbonylcyanide m-chlorophenylhydrazone (CCCP) were used
      to alter energy metabolism. Exposure of cells to 5 mM Amytal did not
      significantly change ATP concentrations but produced transient elevations of
      [Ca2+]i of approximately 80 nM, which were reduced by 32% when cells were studied
      in Ca(2+)-free solutions. CCCP (10 microM) caused a transient reduction in ATP
      concentration of 33%. CCCP also produced sustained elevations of [Ca2+]i of about
      280 nM, which were reduced by 47% when in Ca(2+)-free solutions. In spite of the
      sustained elevation of [Ca2+]i induced by CCCP, NSC-19 showed no reduction in
      cell viability after 48 h compared with controls. Ruthenium red, a blocker of
      Ca2+ uptake by mitochondria, had little effect on the CCCP-induced [Ca2+]i
      increment. KCl or glutamate did not produce significant changes in [Ca2+]i,
      indicating that these cells do not possess significant numbers of voltage
      dependent Ca2+ channels or excitatory amino acid receptor-gated channels. [Ca2+]i
      values in these cells were modified by changes in extracellular Ca2+
      concentrations. In Ca(2+)-containing solutions, inhibition of Na+/Ca2+ exchange
      by amiloride and bepridil led to increased [Ca2+]i, as did blockade of Ca2+
      ATPase by vanadate, suggesting that membrane transporters are important in Ca2+
      efflux in NSC-19. The present studies indicate that exposure of NSC-19 cells to
      Amytal and CCCP produces Ca2+ increments by release from internal stores, as well
      as by transmembrane influx. These results demonstrate that small increments in
      [Ca2+]i can be produced by metabolic inhibitors or other compounds and that such
      changes are not associated with immediate cell death. Changes in [Ca2+]i could
      potentially result in abnormal cell function secondary to altered action of
      Ca(2+)-dependent enzymes.

PMID- 7828082
TI  - Inhibition of nitrovasodilators by pyocyanin and methylene blue is dissociated
      from nitric oxide formation.
AB  - The phenazine pigment pyocyanin (Pyo), like methylene blue (MB), inhibits
      vascular relaxation induced by organic nitrates. These nitrovasodilators are pro
      drugs that have in common the ability to generate nitric oxide (NO). In this
      study, we characterized responses of rabbit isolated aortic ring to 3
      morpholinosydnonimine (SIN-1), S-nitroso-N-acetylpenicillamine (SNAP), sodium
      nitroprusside, glyceryl trinitrate (GTN), and isosorbide dinitrate in the
      presence and absence of 10 microM Pyo. We also examined the effect of Pyo (1 and
      10 microM) and MB (1 and 10 microM) on vasorelaxation induced by authentic NO,
      and finally we tested the effects of Pyo and MB on the tissue-independent
      formation of NO from SIN-1, SNAP, and sodium nitroprusside, using the
      chemiluminescence--headspace gas method. Pyo (10 microM) surmountably inhibited
      aortic responses to GTN, isosorbide dinitrate, SIN-1, and SNAP with a
      characteristic rightward shift of the dose-response curve; the apparent EC50 of
      these drugs for relaxation of phenylephrine-contracted aorta was increased 18-, 4
      , 13-, and 15-fold, respectively. Pyo (1 and 10 microM) and MB (10 microM)
      inhibited NO-induced vasorelaxation at the EC50 of NO by 35, 72, and 56%. In
      contrast, Pyo did not inhibit sodium nitroprusside induced vasodilation. For a 10
      min incubation, 10 microM Pyro or MB increased NO production from SNAP 1.8- and
      2.9-fold, respectively, and increased NO production from SIN-1 by 3.8- and 7.1
      fold, respectively. Neither Pyo nor MB enhanced NO formation from sodium
      nitroprusside. These data indicate that Pyo and MB inhibit nitrovasodilator
      induced relaxation of aortic ring by interfering with the action of NO,
      subsequent to its formation.

PMID- 7828083
TI  - Effect of vanadium compounds on calmodulin activity in experimental diabetes in
      rats.
AB  - Vanadate and vanadyl have been reported to have insulin-like properties and have
      recently been demonstrated to be beneficial in the treatment of diabetic animals.
      In this study, we determined whether vanadium ions mimic the effect of insulin on
      calmodulin activity of liver and adipose tissues in streptozotocin-induced
      diabetic rats and examined their effect with respect to concentration and time.
      Calmodulin activities in the hormone-sensitive tissues decreased in diabetes and
      returned to normal after sodium metavanadate or vanadyl sulfate treatment for 3
      weeks (0.2, 0.4, and 0.8 mg/mL in drinking water). These results demonstrate that
      V5+ and V4+ forms of vanadium can restore the activity of calmodulin in
      experimental diabetes induced by streptozotocin.

PMID- 7828084
TI  - Comparison of calcium absorptive and secretory capacities of segments of intact
      or functionally resected intestine during normo-, hypo-, and hyper-calcemia.
AB  - Absorptive and secretory capacities of six in situ intestinal loops of equal
      length were compared under the same calcium load and calcemic condition. The
      highest rate of calcium absorption was found in duodenum, colon, and proximal
      jejunum when loops were filled with 0.3 mM calcium, and in duodenum and proximal
      jejunum when filled with 10 mM luminal calcium. Secretory rates were in the
      following order: duodenum, jejunum, proximal jejunum, cecum, ileum, and proximal
      colon. Absorption of 0.3 mM calcium was decreased in all but the cecum and colon
      during hypercalcemia, and in duodenum, proximal jejunum, and colon during
      thyroparathyroidectomy-induced hypocalcemia. In contrast, calcium secretion was
      directly related to plasma calcium concentration and the length of the intestine.
      Functional resection of any part met with a compensatory increase in calcium
      absorption by the remaining segments, with the exception of the resection of the
      distal ileum with the large bowel. In conclusion, proximal small intestine
      exhibited the highest rate of absorption and secretion, but functional resection
      of this or any part did not affect the overall calcium absorption if luminal
      calcium was 10 mM. Moreover, enhanced secretion and reduced absorption during
      hypercalcemia were beneficial with respect to plasma calcium regulation.

PMID- 7828085
TI  - Fructose loading induces cardiovascular and metabolic changes in nondiabetic and
      diabetic rats.
AB  - The effects of fructose loading on the integrated cardiovascular function in
      vivo, glycemic control, glucose tolerance, and plasma lipid levels in nondiabetic
      and streptozotocin (STZ) diabetic rats were investigated. Endothelial morphology
      of the thoracic aorta was also assessed with scanning electron microscopy.
      Fructose-loaded nondiabetic rats exhibited elevated blood pressure and pulse
      rate, and signs of arterial atherogenesis, such as focal adherence of leukocytes
      and fibrin to the endothelium. Intraperitoneal glucose tolerance tests revealed a
      greater increase in plasma insulin in response to glucose challenge in these
      animals than in the control. Compared with the untreated STZ-diabetic animals,
      fructose-loaded diabetic rats had significantly greater hyperglycemia, glucose
      intolerance, and hyperlipidemia and higher blood pressure, but had a similar
      degree of hypoinsulinemia, cardiac dysfunction, and cardiac enlargement. They
      also showed signs of early atherogenesis. The central venous pressure and the
      susceptibilities of the rats to the induction of ventricular arrhythmias by
      intravenous infusion of aconitine were not significantly affected by either STZ
      injection or fructose loading. It is concluded that prolonged intake of an
      excessive amount of fructose has detrimental effects on the cardiovascular
      system, glucose metabolism, and plasma lipid levels in both nondiabetic and STZ
      diabetic rats.

PMID- 7828086
TI  - Renal perfusion pressure and renin secretion in bilaterally renal denervated
      sheep.
AB  - To further investigate the influence of renal nerves on renin secretion, the
      renin secretion responses to step reductions of renal perfusion pressure (RPP)
      were studied in conscious sheep with innervated kidneys (n = 5) and with
      bilaterally denervated kidneys (n = 5). The average basal level of RPP in sheep
      with denervated kidneys (82 +/- 4 mmHg; 1 mmHg = 133.3 Pa) was similar to that in
      sheep with innervated kidneys (83 +/- 3 mmHg). RPP was reduced in four sequential
      15-min steps, to a final level of 54 +/- 2 mmHg in sheep with innervated kidneys
      and to 57 +/- 1 mmHg in denervated sheep. The renin secretion rate was increased
      as RPP was reduced in sheep with innervated kidneys. Baseline peripheral plasma
      renin activity was reduced and there was almost no response of renin secretion
      rate to reduction of RPP in sheep with denervated kidneys. Also, baseline renal
      blood flow, urine flow rate, sodium excretion rate, and potassium excretion rate
      were higher in sheep with denervated kidneys than those with innervated kidneys.
      Baseline plasma angiotensin II was similar in both groups of sheep. As RPP was
      decreased, plasma angiotensin II was increased in sheep with innervated kidneys,
      but was not RPP or renal denervation. In conclusion, hormonal factors, such as
      angiotensin II and atrial natriuretic factor, do not account for the dramatic
      suppression of renin secretion in response to the reduction of RPP in sheep with
      bilateral renal denervation. Renal nerves are a necessary component in the
      control of renin secretion during reduction of RPP and may contribute to the
      regulation of baseline plasma renin activity and sodium excretion rate in
      conscious ewes.

PMID- 7828087
TI  - Pyridostigmine bromide does not alter thermoregulation during exercise in cold
      air.
AB  - This study examined the effects of acute and chronic pyridostigmine bromide (PB)
      administration on thermoregulatory and metabolic responses to exercise in cold
      air (5 degrees C). Seven healthy men completed two 7-day trials in a double
      blind, crossover experimental design: during one trial they received PB (30 mg
      three times daily) and during the other trial they received placebo. For each
      trial, subjects attempted four (3 h) exercise tests: low-intensity exercise
      (approximately 25% VO2max) and moderate-intensity exercise (approximately 50%
      VO2max), on days 2 and 3 and again on days 6 and 7. Metabolic rate, body
      temperatures, and venous blood samples were obtained before and during exercise.
      Red blood cell acetylcholinesterase inhibition induced by PB increased (p < 0.05)
      from 34% on day 1 to 43% on days 3-7. Metabolic rate, body temperatures, and
      regional heat conductance responses were not different between trials. Plasma
      glucose, glycerol, free fatty acid, lactate, sodium, and potassium concentrations
      were not different between trials. In addition, differences were not found
      between acute and chronic experiments for any thermoregulatory or metabolic
      responses. These findings demonstrate that the PB dosage used by military
      personnel, as a pharmacological defense against nerve-agent poisoning, should not
      cause any adverse thermoregulatory or metabolic effects during moderate activity
      in cold climates.

PMID- 7828088
TI  - In vitro response of rat renal artery to perfusion pressure.
AB  - Both tubuloglomerular feedback and a myogenic response contribute to
      autoregulation of renal blood flow. Vascular interaction initiated by
      tubuloglomerular feedback has been described and prevents definition, in vivo, of
      the contribution of myogenic responses to autoregulation. Segments of rat renal
      artery were perfused in vitro at constant flow while upstream and downstream
      pressures were measured on-line, allowing determination of resistance. Transmural
      pressure was governed by a downstream resistor. Outside diameter was measured by
      an ocular micrometer. The segments were bathed in bicarbonate Ringer solution and
      perfused with Ringer containing 50 g/L bovine serum albumin. Potassium
      depolarization reduced the diameter and made it more sensitive to perfusion
      pressure. Serosal norepinephrine, 10(-7)-10(-5) M, caused graded constriction and
      increased the axial pressure drop due to vessel resistance. Addition to the
      perfusate of rat red blood cells to hematocrit approximately 33% significantly
      reduced arterial diameter and enhanced the increased axial pressure drop induced
      by 10(-6) M norepinephrine. Sequential elevation of perfusion pressure from 50 to
      100 mmHg (1 mmHg = 133.3 Pa) increased the diameter significantly. Red cells
      reduced the slope of the diameter-pressure relationship. In another experiment,
      norepinephrine reduced the slope of diameter versus perfusion pressure, while 10(
      4) M papaverine plus norepinephrine increased the slope, compared with
      norepinephrine alone. Norepinephrine caused a sizable axial pressure drop (15.7
      +/- 3.7 mmHg), which decayed as perfusion pressure increased; the decay was
      accentuated by papaverine. The changes in axial pressure drop were linearly
      related to the inverse 4th power of diameter, indicating that both measurements
      assessed the same behavior. Several different maneuvers thus affect the
      relationship between arterial diameter and perfusion pressure, and the
      relationship between axial pressure drop and perfusion pressure. The results
      indicate the presence of a myogenic response, which is, however, not strong
      enough to defend vessel diameter when pressure rises.

PMID- 7828089
TI  - Differential effects of pinacidil and cromakalim on vascular relaxation and
      sympathetic neurotransmission.
AB  - We tested the hypothesis that pinacidil and cromakalim acted at different sites
      to relax vascular smooth muscle, in vitro. We compared the effects of pinacidil
      and cromakalim on tension development in isolated canine and bovine pulmonary
      artery and vein and canine mesenteric artery and dorsal metatarsal vein, and on
      the pre- and post-synaptic responses of the canine blood vessels to transmural
      nerve stimulation. Both pinacidil and cromakalim relaxed bovine and canine blood
      vessels precontracted to 50% of maximal tension with U46619, prostaglandin F2
      alpha, or norepinephrine. Pinacidil- and cromaklim-mediated relaxations of the
      blood vessels were not mediated by endothelium-derived factors, prostanoids,
      muscarinic receptors, beta-adrenoceptors, or Ca(2+)-activated or voltage
      dependent K+ channels, since they were unaffected by endothelium-rubbing,
      indomethacin, L-NG-monomethyl-L-arginine, atropine, propranolol, and
      charybdotoxin. Glibenchlamide, an inhibitor of ATP-activated K+ channels (K+ATP),
      and KCl (25-60 mM) sufficient to minimize the role of K+ channels almost
      abolished cromakalim- but not pinacidil-induced relaxation of the blood vessels.
      Pinacidil inhibited the contractions of the dorsal metatarsal vein and mesenteric
      artery to norepinephrine and transmural nerve stimulation and the efflux of 2
      [14C]norepinephrine during transmural nerve stimulation. In contrast, 1 and 10 nM
      cromakalim enhanced while 0.1 and 1 microM cromakalim inhibited the contractions
      of, and 2-[14C]norepinephrine efflux from, the mesenteric artery and dorsal
      metatarsal vein during transmural nerve stimulation. Thus, pinacidil and
      cromakalim relax smooth muscle by stimulation of K+ATP channels. Pinacidil also
      relaxes the blood vessels by a K+ channel independent mechanism. Pinacidil
      induced relaxation may also result from presynaptic inhibition of norepinephrine
      release from the sympathetic neuron.

PMID- 7828090
TI  - Effect of torbafylline on muscle blood flow, performance, and capillary supply in
      ischemic muscles subjected to varying levels of activity.
AB  - Torbafylline, a novel xanthine derivative, was given to rats by gavage (2 x 25
      mg.kg-1.day-1, morning and evening) to study its effect upon fast muscles
      (tibialis anterior and extensor digitorum longus) made ischemic by unilateral
      ligation of the common iliac artery and subjected to two types of activity
      imposed by chronic electrical stimulation at 10 Hz: (i) strenuous, 6 h.day-1 as 3
      x 2 h with 90- to 120-min intervals or (ii) mild, 105 min.day-1 as 7 x 10-15 min
      with 90- or 85-min intervals for 12-14 days. Some of the deleterious effects on
      ischemic muscles of strenuous activity (reduced blood flow during contractions,
      less resistance to fatigue) were remedied by torbafylline treatment, and values
      normalized. Most notably, torbafylline significantly reduced the degree of
      capillary endothelial cell swelling. In addition, the degree of atrophy was
      reduced and fatigue resistance improved in muscles contralateral to ischemic,
      which had been impaired with the strenuous regime. Torbafylline treatment had
      little further effect on ischemic muscles subjected to mild stimulation, which on
      its own improved functional hyperemia, resistance to fatigue, and the capillaries
      per fibre ratio in tibialis anterior, although it did significantly increase the
      capillary per fibre ratio in extensor digitorum longus. These data indicate a
      possible role for torbafylline as an adjunct to exercise therapy for chronic
      muscle ischemia.

PMID- 7828091
TI  - Acid-base regulation: a comparison of quantitative methods.
AB  - The [H+] and [HCO3-] of biological solutions is determined by the PCO2, the
      concentration of strong ions (mainly Na+, K+, Ca2+, Cl-, lactate-), and the
      concentration of weak acids (mainly proteins, phosphates). Two mathematical
      models are available that use a quantitative approach to describe the acid-base
      behaviour of plasma, but which differ in their treatment of the weak acid
      component: Stewart model (using PCO2, strong ion difference (SID = [Na+ + K+ +
      Ca2+] - [Cl- + lactate-]) and [protein]TOT); Fencl model (using PCO2, SID,
      [albumin], and [Pi]TOT). The present study compared measured and estimated [H+]
      and [HCO3-] in whole-blood samples collected from eight subjects during two
      double-ramp exercise protocols to the limit of tolerance to assess the accuracy
      with which each of the quantitative models predicts measured values. Arterialized
      venous blood was analyzed for [H+], PCO2, [protein]TOT, [albumin], [Pi]TOT, and
      SID (= [Na+ + K+ + Ca2+] - [Cl- + lactate-]), and these independent variables
      were then substituted into the appropriate mathematical model to estimate [H+]
      and [HCO3-]. Analysis showed that the [H+] and [HCO3-] estimated using either
      model provided a good estimate of the [H+] (Stewart model, r = 0.81; Fencl model,
      r = 0.81) and [HCO3-] (Stewart model, r = 0.93; Fencl model, r = 0.93) measured
      in plasma; linear regression analysis demonstrated that the slopes and intercepts
      for each of the relationships were not different (p > 0.05) from the line of
      identity. Differences between estimated and measured values were small, averaging
      < 3 nmol.L-1 for [H+] and < 2 mmol.L-1 for [HCO3-].(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7828092
TI  - Enhanced metabolism of glucose and glutamine in mesenteric lymph node lymphocytes
      from spontaneously diabetic BB rats.
AB  - Increased energy substrate metabolism accompanies the functional activation of
      extrathymic immunocytes in the autoimmune BB diabetic rat, but the specific cells
      responsible have not been identified. To determine the possible contribution of
      lymphocytes to the elevated metabolism of glucose and glutamine, mesenteric lymph
      node cells were selected because they contain few macrophages or natural killer
      (NK) cells. Results from diabetic (BBd, n = 7) and non-diabetes-prone (BBn, n =
      7) rats were compared with those from streptozotocin-induced diabetic (STZ-BBn, n
      = 6) rats. In BBd cells, all measured metabolites of glutamine (CO2, glutamate,
      aspartate, and NH3) in the presence of 5 mM glucose were elevated (1.5- to 2.5
      fold) compared with BBn. In contrast, the only product of glucose metabolism (in
      the presence of 2 mM glutamine) that was increased was pyruvate (1.6-fold). All
      measured products of glucose metabolism were significantly lower in cells from
      STZ-BBn than from BBn rats. Products from glutamine did not differ. Calculated
      potential ATP production was greater (p < 0.05) in BBd than in BBn and STZ-BBn
      cells (86 +/- 5 vs. 65 +/- 2 and 53 +/- 5 nmol.2 h-1 x 10(-6) cells,
      respectively). However, in BBn and STZ-BBn rats, about three quarters of the
      cells were T (CD5+) cells and one quarter were B (MARK-1+) cells, whereas in BBd
      three quarters of the cells were MARK-1+.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7828093
TI  - Treatment of elderly patients with delirium.

PMID- 7828094
TI  - Surveillance of medical students for TB urged.

PMID- 7828095
TI  - Lap-belt injury could result from improper use.

PMID- 7828096
TI  - The incredible machine?

PMID- 7828097
TI  - Home versus hospital death: assessment of preferences and clinical challenges.
AB  - In Canada hospital beds have been reduced in number, and there is increased
      fiscal pressure for patients with advanced terminal illness to be cared for in
      their own homes until death. In this issue (see pages 361 to 367) Drs. Ian R.
      McWhinney and Martin J. Bass and Ms. Vanessa Orr report that people who die at
      home rather than in hospital are more likely to be cared for by family members
      other than a spouse and to have the services of a private duty nurse. The
      literature has shown that health problems of elderly spouses, occupational and
      other responsibilities of family members, and the physical, psychologic and
      financial strain of providing home care can make it difficult to honour a
      terminally ill person's wish to die at home. The findings of McWhinney and
      colleagues point to the existence of a two-tiered health care system in which
      those who have access to private duty nursing are able to stay at home to die.
      Their study also raises three key questions that must be addressed in the
      assessment of patient preferences as to place of death: Should family members be
      included in the assessment? How should preferences be measured? and What is an
      appropriate time frame for such an assessment? Although McWhinney and colleagues
      identify characteristics of care associated with place of death and underline the
      need for careful assessment of patient preferences regarding place of death,
      further research is needed to build on these findings. In the current context of
      health care reform, we need to examine more closely the type and intensity of
      services needed to support patients and their families in the final stages of a
      terminal illness.

PMID- 7828099
TI  - Basic statistics for clinicians: 3. Assessing the effects of treatment: measures
      of association.
AB  - In the third of a series of four articles the authors show the calculation of
      measures of association and discuss their usefulness in clinical decision making.
      From the rates of death or other "events" in experimental and control groups in a
      clinical trial, we can calculate the relative risk (RR) of the event after the
      experimental treatment, expressed as a percentage of the risk without such
      treatment. The absolute risk reduction (ARR) is the difference in the risk of an
      event between the groups. The relative risk reduction is the percentage of the
      baseline risk (the risk of an event in the control patients) removed as a result
      of therapy. The odds ratio (OR), which is the measure of choice in case-control
      studies, gives the ratio of the odds of an event in the experimental group to
      those in the control group. The OR and the RR provide limited information in
      reporting the results of prospective trials because they do not reflect changes
      in the baseline risk. The ARR and the number needed to treat, which tells the
      clinician how many patients need to be treated to prevent one event, reflect both
      the baseline risk and the relative risk reduction. If the timing of events is
      important--to determine whether treatment extends life, for example--survival
      curves are used to show when events occur over time.

PMID- 7828098
TI  - Safety and effectiveness of the new inactivated hepatitis A virus vaccine.
AB  - PURPOSE: To examine the evidence concerning the safety and effectiveness of the
      inactivated hepatitis A virus vaccine recently licensed for use in Canada. DATA
      SOURCES: The main source of information were papers presented at the
      International Symposium on Active Immunization against Hepatitis A, held in
      Vienna, Austria, Jan. 27-29, 1992. The bibliographies of these papers were
      searched for additional references. Recent articles describing the new vaccine
      and the epidemiologic aspects of infection with hepatitis A virus (HAV) were also
      reviewed. STUDY SELECTION: Peer-reviewed reports of trials approved by a
      government regulatory agency on the safety, immunogenic properties and efficacy
      of the vaccine. DATA EXTRACTION: The authors assembled key reports on adverse
      reactions, protection from disease and serologic assessment of immune response in
      vaccine recipients; data from these reports were tabulated and analysed. RESULTS
      OF DATA SYNTHESIS: The new vaccine contains the HM175 strain of HAV, which is
      adapted to grow in tissue culture. The virus is purified, inactivated with the
      use of formaldehyde and adsorbed onto aluminum hydroxide. The recommended dose
      for adults is 720 enzyme-linked immunosorbent assay (ELISA) units in a 1.0-mL
      dose and for children 360 ELISA units in a 0.5-mL dose, injected intramuscularly.
      The usual schedule is three serial doses, the second given 1 month and the third
      6 to 12 months after the initial dose. Reported side effects are infrequent and
      minor. In healthy persons who have received two doses, the seroconversion rate is
      almost 100%. Protective efficacy after two doses is estimated to be 94%. However,
      the persistence of protective antibodies has been studied only over the short
      term (3 years). CONCLUSIONS: The new HAV vaccine is safe, effective and best
      suited to pre-exposure prophylaxis in people with an increased risk of infection
      for an extended period, such as travellers to areas where the disease is endemic.
      Further studies are needed to determine whether infants respond well to the
      vaccine and whether the vaccine protects recipients from subclinical infection
      and associated fecal shedding of HAV. Controlled trials to determine the duration
      of protection beyond 3 years and the effects of more rapid dosage schedules are
      also needed.

PMID- 7828100
TI  - Grand rounds: a paradox in medical education.
AB  - OBJECTIVES: To assess perceptions of the importance and educational purpose of
      hospital grand rounds among physicians with administrative responsibilities, and
      to examine organizational aspects of grand rounds as educational events. DESIGN:
      Descriptive survey by mailed nonanonymous questionnaire. SETTING: All hospitals
      of more than 100 beds in Calgary. PARTICIPANTS: A total of 150 residency program
      directors and directors of departments and divisions in hospitals with differing
      teaching functions. RESULTS: A total of 120 questionnaires (80%) were returned,
      and the responses of 107 physicians were analysed. Each year in Calgary formal
      grand rounds activities occupy auditoriums and seminar rooms for more than 2000
      hours. Most respondents considered grand rounds to be the main hospital-based
      continuing medical education activity in their discipline. Aspects of grand
      rounds considered to be important were updates in research, diagnosis and
      management, and only one third of the respondents felt that actual patient
      problems should always be the focus of discussion. The organization and planning
      of grand rounds revealed a paradox: despite the perceived educational importance,
      only 13% of rounds were based on a curricular structure, and 16% were based on
      needs assessments. The grand rounds topic was most often the choice of the
      presenter. CONCLUSIONS: The quantity of time devoted to grand rounds suggests
      importance in the routine workings of hospital departments. Grand rounds are used
      as a showcase for excellence in medical care or recent medical advances. It is
      paradoxical, therefore, that little interest appears to be shown in educational
      structure such as curriculum or evaluation of learning. Professional interaction
      is an inherent objective of traditional grand rounds. Further evaluation of the
      purpose and educational efficacy of traditional grand rounds is suggested.

PMID- 7828101
TI  - Statement on travellers and HIV/AIDS.

PMID- 7828102
TI  - Off the prescription pad and over the counter: the trend toward drug deregulation
      grows.
AB  - In the future, regulatory agencies may authorize the switch of more drugs from
      prescription-only to over-the-counter status. This could have the double effect
      of reducing the number of doctor visits and cutting drug costs. Although some
      physicians worry about the escape of reasonably potent drugs from medical
      surveillance, pharmacists are assuming a more significant counselling and
      medication-tracking role. This article looks at the negative and positive sides
      of drug deregulation from the perspectives of the physician, pharmacist and
      patient.

PMID- 7828103
TI  - It is time for organized medicine to put out the welcome mat for women.

PMID- 7828104
TI  - Furore over language, shortage of women leaders signs of need for change at CMA,
      committee says.
AB  - Negative comments made recently about use of the term "chair" instead of
      "chairman," and the continuing shortage of women at decision-making levels of
      organized medicine are ample evidence that the work of the CMA's Gender Issues
      Committee (GIC) is not done, says the committee chair, Dr. May Cohen. At its fall
      meeting, the GIC said the CMA should actively promote greater representation by
      women physicians on its political and expert committees; a target of at least 25%
      membership within the next 2 to 5 years was suggested. The committee discussed
      other measures the CMA should consider in its attempts to become more
      representative of Canada's physician population.

PMID- 7828105
TI  - Staffing shortfall plagues radiation oncology.
AB  - Canada's radiation oncologists say a staffing crisis looms within their
      specialty. A growing number of cancer patients means resources are being
      stretched, doctors are facing additional stress and waiting lists are becoming
      longer. "I see no way that we can conceive of meeting our needs by 2000," says
      Dr. Tom Keane of Toronto's Princess Margaret Hospital. The staffing shortage also
      extends to the medical physicists who run the radiotherapy machines. Many are
      being attracted to the US by higher salaries.

PMID- 7828106
TI  - "Scientific" chiropractors hope to improve status of chiropractic within
      scientific community.
AB  - A new group has been formed to represent chiropractors and other health care
      professionals who limit their use of spinal manipulation to the treatment of back
      problems, and who oppose claims that chiropractic can treat problems such as
      asthma and enuresis. However, some Canadian chiropractors respond that most
      claims that chiropractic can cure disease originate in the US, and that Canadian
      chiropractors are conservative in their claims. Some Canadian pediatricians are
      concerned that chiropractors are attempting to treat more children.

PMID- 7828107
TI  - Proposal for Canadian-style single-payer health care receives cool reception in
      US.
AB  - Is health care reform dead in the US? It may be, if the reception given President
      Clinton's reform plan and a proposal for a single-payer program in California is
      any indication. There has been a dramatic move to the right south of the border,
      where people have lined up to oppose "big government" and additional government
      programs. Still, American proponents of a single-payer program similar to
      Canada's insist that the battle for reform is not yet over.

PMID- 7828108
TI  - University researchers propose major reforms to cut health care costs.
AB  - Canada could slash public-health expenditures by 15% with no reduction in
      Canadians' health status by substituting less costly types of delivery and forms
      of treatment in more appropriate settings, says the recently released report of
      the Queen's-University of Ottawa Project on Cost-effectiveness of the Canadian
      Health Care System. Sustainable Health Care for Canada concludes that the system
      could be made more efficient by reducing the number of acute-care beds and
      cutting patients' length of stay in hospital. It also suggests substituting
      continuing care for acute care and relying less on institutionalization of the
      elderly and more on alternatives such as residential or community care. The
      report also suggests that as Canada experiments with decentralization, it may be
      time to look at other regulatory models for health care, including the mixed
      market approach.

PMID- 7828109
TI  - U of T Medical School uses multistep strategy to prevent sexual harassment.
AB  - The University of Toronto medical school is using a multistep strategy in an
      attempt to prevent sexual harassment among students and faculty members. A
      driving force behind the program is Dr. Miriam Rossi, who was recently appointed
      associate dean of student affairs. As well, the dean of medicine sent a notice to
      faculty members explaining that there will be zero tolerance "for any behaviour
      that can be construed to be sexual harassment."

PMID- 7828110
TI  - Symptom attribution in cultural perspective.
AB  - The explanatory model perspective of medical anthropology emphasizes the cultural
      shaping of individuals' efforts to make sense of their symptoms and suffering.
      Causal attribution is a pivotal cognitive process in this personal and social
      construction of meaning. Cultural variations in symptom attribution affect the
      pathogenesis, course, clinical presentation and outcome of psychiatric disorders.
      Research suggests that styles of attribution for common somatic symptoms may
      influence patients' tendency to somatize or psychologize psychiatric disorders in
      primary care. At the same time, symptom attributions are used to negotiate the
      sociomoral implications of illness. Recent work in social psychology and medical
      anthropology emphasizes the roots of attributional processes in bodily and social
      processes that are highly context-dependent, and hence, must be understood as
      part of the construction of a local world of meaning. Symptom attributions then
      may be understood as forms of positioning with both cognitive and social
      consequences relevant to psychiatric assessment and intervention.

PMID- 7828111
TI  - Factors complicating the diagnosis of depression in cerebrovascular disease, Part
      I--Phenomenological and nosological issues.
AB  - Depression is frequently associated with cerebrovascular disease. Early detection
      and intervention in depression may enhance rehabilitation potential. Difficulties
      encountered by clinicians in identifying depression in patients with
      cerebrovascular disease are numerous. This two part review focuses on issues
      related to the diagnosis of depression with emphasis on recognition of depressive
      symptoms and their relevance to the diagnosis of depressive syndromes in the
      presence of vascular lesions and associated neurological deficits. Furthermore,
      the value of diagnostic instruments and biological markers in identifying
      depression following stroke has been critically evaluated. In this first part of
      this two part paper, phenomenological and nosological aspects are considered with
      an emphasis on symptom profile, significance of vegetative symptoms and other
      related emotional responses such as catastrophic reaction, emotionalism and
      apathy in the diagnosis of depression following stroke. The applicability of
      diagnostic subcategories to define depressive syndromes associated with
      cerebrovascular disease and its clinical relevance is also discussed. The authors
      stress that knowledge on phenomenology of depression and other emotional
      responses related to cerebrovascular disease will facilitate better understanding
      of its clinical presentation and may improve diagnostic acumen.

PMID- 7828112
TI  - Psychosocial impact of laryngectomy mediated by perceived stigma and illness
      intrusiveness.
AB  - In addition to prolonging life, successful treatment by laryngectomy also results
      in functional disability (loss of speech) and physical disfigurement (stoma). It
      was hypothesized that these after-effects contribute to perceived stigma which,
      in turn, compromises quality of life. The hypothesis that the psychosocial impact
      of perceived stigma operates through illness intrusiveness--illness-induced
      disruptions that interfere with continued involvements in valued activities and
      interests--was tested. Data were collected from 51 laryngectomy recipients via
      standardized interviews. As hypothesized, results indicated that: 1. both
      perceived stigma and illness intrusiveness are related to psychosocial well-being
      and emotional distress; 2. illness intrusiveness mediates the relation between
      perceived stigma and psychosocial outcomes; 3. the psychosocial impact of illness
      intrusiveness is most devastating in the context of highly stigmatized self
      perception; and 4. unique profiles of illness intrusiveness across individual
      life domains may be associated with specific psychosocial outcomes. Findings are
      discussed in relation to the hypothesis that illness intrusiveness is a common
      underlying determinant of the psychosocial impact of chronic illness.

PMID- 7828113
TI  - The impact of pain and impaired role performance on distress in persons with
      cancer.
AB  - The observed upward trend in the incidence of many cancers is expected to
      continue for the next 20 years despite monumental basic research efforts. There
      are interpersonal and intrapsychic complications associated with cancer and its
      treatment leading to considerable distress which, in extreme cases, becomes
      clinical depression and anxiety. Pain and impaired role performance have been
      cited as being important sources of distress in people with cancer. This paper
      presents data from a community sample of 1,309 people living with cancer in
      Prince Edward Island, Manitoba and Quebec and examines risk factors for cancer
      related distress. In the model tested in this paper, pain and other symptoms and
      treatment side-effects as well as cancer-related fears were seen to have direct
      and indirect effects on psychological symptoms of distress. Impaired role
      performance was a central mediator for the indirect effects. The model explained
      34% of the variance in distress scores (General Health Questionnaire) and was
      equally applicable to all three study sites, both male and female subjects, rural
      and urban settings, and to all stages of illness. Pain was the single most
      important explanatory variable. Impaired role performance had a negative effect
      on distress over and above the effect of pain. The results suggest that
      interventions directed at reducing distress in cancer should also address
      interpersonal issues such as the impact of the illness on family, social network
      a work.

PMID- 7828114
TI  - Parasitic diseases and psychiatric illness.
AB  - Distinguishing parasitic diseases from other infections and tropical medical
      disorders based on microbiological classification is a matter of convenience.
      Organic brain syndromes are associated with both protozoan and helminthic
      infections; side-effects of drugs commonly used to treat parasitoses may impair
      mood and cause anxiety, agitation or psychosis. Emotional states may in turn
      affect the experience of medical illness. Psychiatrically significant features of
      medical illness are determined both by pathophysiology and by the personal and
      social context in which they occur. Many factors affect mental health in the
      tropics where the synergy of infection, emotional strengths, vulnerabilities,
      social supports and stressors is critical. This review discusses parasitic
      diseases of psychiatric interest by virtue of their effects on thinking, mood and
      behaviour; and it distinguishes issues that apply mainly to indigenous
      populations and visitors to endemic areas. In some paradoxical instances the
      psychiatric influence of parasitic diseases does not require infection; the
      review concludes by considering the prime example, delusions of parasitosis,
      which is a primary psychiatric disorder.

PMID- 7828115
TI  - Guidelines for phase IV clinical trials. Joint Committee on Phase IV Clinical
      Trial Guidelines.

PMID- 7828116
TI  - Re: Bradycardia and somnolence after adding fluoxetine to pimozide regimen.

PMID- 7828117
TI  - Student apathy: a footnote in the history of psychiatry or a disorder unique to
      post-adolescence?

PMID- 7828118
TI  - Integrated psychotherapy for the elderly.
AB  - The complexity of interacting variables in the geriatric patient imposes the
      therapeutic necessity to employ all effective therapeutic modalities in an
      interactive and integrated fashion. This paper examines the efficacy data on
      brief and longer term therapies as applied to the elderly, most particularly for
      treatment of depression and bereavement. In determining the development of an
      integrated psychotherapy treatment plan, the author suggests a decision pathway
      which incorporates concurrent utilization of theoretical principles derived from
      psychodynamic, interpersonal and cognitive behavioural theory. This tripartite
      approach informs the assessment and diagnosis of the patient as well as the
      specific choice of therapy. Directions for further research are suggested.

PMID- 7828119
TI  - Geriatric psychiatry consultation in the community.
AB  - While increasing emphasis is being placed on geriatric psychiatry consultation
      and outreach services, there is considerable variation in terms of the
      composition and direction of these programs. Programs vary in terms of their
      objectives, location, target population, use of health professions and other
      resources and their method of consultation. The purposes of this paper are to
      review the characteristics of existing programs, to review the needs of the
      targets of consultation and to consider theoretical and methodological approaches
      which have been found to be useful in mental health/psychiatric consultation, in
      continuing medical education, and in program evaluation. On the basis of this
      review, future directions for effective approaches to consultative outreach in
      geriatric psychiatry will then be proposed.

PMID- 7828120
TI  - Progress in geriatric psychiatry.

PMID- 7828121
TI  - An update on elder abuse and neglect.
AB  - Abuse and neglect of the elderly represent an important social problem in Canada.
      Forms of elder abuse and neglect include physical, psychological and material
      abuse; neglect, both intentional and unintentional; and violation of legal
      rights. The definitions, signs, and symptoms of elder abuse and neglect are
      discussed, as are estimates of incidence and prevalence, and descriptions of
      possible risk factors. The evolution of legislation regarding the reporting of
      elder abuse and neglect is reviewed, as are relevant areas of common law, the
      Civil Code, and the Criminal Code. This is followed by an overview of practical
      considerations in clinical management, and finally by recommendations for further
      research.

PMID- 7828122
TI  - The future of geriatric psychiatry.
AB  - The author first reviews some of the main forces and historical developments that
      have shaped the young specialty of geriatric psychiatry. Emphasis is placed on
      the integrative and collaborative nature of the psychiatry of old age. This
      includes its relationship with the parent field of psychiatry, geriatric medicine
      and the broader field of gerontology. An outline of the future for the field is
      presented which highlights the need for academic credibility and responsiveness
      to service delivery issues. Because future trends in mental health delivery are
      likely to continue to give priority to the severely mentally ill and to emphasize
      cost-effectiveness, geriatric psychiatrists are well poised to meet the
      challenges of the coming generation. However, a strong future depends ultimately
      on the ability of the field to recruit bright young psychiatrists who bring
      inquisitiveness, enthusiasm and a social commitment to a vulnerable elderly
      population.

PMID- 7828123
TI  - Recent developments in geriatric psychopharmacotherapy.
AB  - This paper highlights recent advances in the pharmacological management of
      geriatric affective disorders and dementia. The current roles of tricyclic
      antidepressants, selective serotonin reuptake inhibitors (SSRIs) and monoamine
      oxidase inhibitors (MAOIs) in the treatment of depression in old age are
      discussed. Recent findings pertaining to continuation and maintenance of
      antidepressant treatment are also addressed. The treatment of bipolar affective
      disorder in the elderly has received much less study than has unipolar
      depression. A number of issues relating to efficacy, side-effects and optimal
      blood levels of lithium, carbamazepine and valproate in bipolar disorder remain
      unresolved and await further study. Finally, drug treatment of the cognitive
      impairment and psychiatric complications of Alzheimer's disease is reviewed.

PMID- 7828124
TI  - Optimization of radiotherapy for patients with cranial chordoma. A review of dose
      response ratios for photon techniques.
AB  - BACKGROUND: Cranial chordomas arise adjacent to critical neural tissues within
      the notochordal remnants in the clivus, frequently compromising adequate surgical
      removal of the primary tumor and making difficult the delivery of an adequate
      dose of radiotherapy. The optimal dose and fractionation have not been
      established. METHODS: The results of radiation combined with surgery, radiation
      alone, and surgery alone were compared based on the cases of 159 patients
      reported in the literature. An analysis of the optimal biologically equivalent
      doses (BED) was performed using the linear-quadratic formula on 47 patients.
      RESULTS: Past techniques using conventional photon irradiation have shown no dose
      response relationship. Survival is improved for patients undergoing surgery
      followed by radiotherapy. CONCLUSION: Combined surgery and postoperative
      radiation is preferable to radiotherapy or surgery alone for management of
      cranial chordoma. Newer radiotherapeutic approaches will allow increased dose
      delivery to the target volume without an anticipated increase in radiation
      morbidity. It is believed that this will increase tumor control. Recent results
      of studies using charged particle therapy in cranial chordoma suggest that this
      may be an alternative way to optimize radiotherapy.

PMID- 7828125
TI  - Epithelial noncarcinoid tumors and tumor-like lesions of the appendix. A
      clinicopathologic study of 184 patients with a multivariate analysis of
      prognostic factors.
AB  - BACKGROUND: The current understanding of appendiceal epithelial tumors is based
      on series composed of relatively small numbers of patients and on case reports.
      The aim of this study was to perform clinicopathologic correlation, particularly
      concerning prognosis, on a relatively large series of patients with epithelial
      tumors and tumor-like lesions of the human vermiform appendix. METHODS: One
      hundred eighty-four cases of simple mucoceles, hyperplastic polyps, adenomas,
      carcinomas, and mucinous tumors of uncertain malignant potential (UMP) were
      reviewed. Retrospective follow-up data were obtained in carcinoma and UMP tumor
      cases. RESULTS: Most neoplasms were of the mucinous type characteristic of the
      appendix, but a small fraction were nonmucinous and resembled neoplasms typical
      of the spectrum encountered in the colorectum. Both benign and malignant
      conditions in some cases showed acellular mucin dissecting the appendiceal wall
      and mucin outside the appendix. Immunostains were sometimes helpful in
      identifying epithelial cells within mucus, but hematoxylin and eosin and mucin
      stains were adequate in most cases. Two factors were significantly associated
      with survival by multivariate analysis: the presence of mucin outside the right
      lower quadrant of the abdomen and the presence of epithelial cells in the
      peritoneal cavity outside the appendix. CONCLUSIONS: The distribution of mucin
      within the abdomen and the presence of cells outside the visceral peritoneum of
      the appendix are important prognostic factors that should be recorded in these
      neoplasms. Tumors designated as UMP lesions behave in a benign or low grade
      fashion.

PMID- 7828126
TI  - Continuous infusion fluorouracil/leucovorin and bolus mitomycin-C as a salvage
      regimen for patients with advanced colorectal cancer.
AB  - BACKGROUND: No effective systemic salvage therapy exists for patients with
      advanced colorectal cancer who progress after receiving bolus fluorouracil (FU)
      and leucovorin (LV) chemotherapy. In vitro data suggest that bolus FU resistance
      can be overcome by continuous infusion (CI) FU, and that the cytotoxic effects of
      Mitomycin-C (MMC) and FU are synergistic. Based on this data, a Phase II trial of
      CI FU and LV with bolus MMC in patients with advanced colorectal carcinoma who
      progressed on only one previous chemotherapy regimen was performed. METHODS:
      Twenty-eight patients with advanced colorectal carcinoma who had progressed after
      one previous chemotherapy regimen of bolus FU/LV were treated with bolus MMC 10
      mg/m2 every 6 weeks and CI FU 200 mg/m2/day admixed with LV 10 mg/m2/day given 14
      days on/7 days off. RESULTS: The partial response rate in 24 evaluable patients
      was 17% (95% confidence interval, 2-32%) with a median response duration of 9.5
      months (range, 4.2-12.0 months). Twelve (50%) additional patients achieved
      disease stabilization. Median survival was 9.9 months in the whole group (28
      patients) and 11.5 months in the 24 evaluable patients. The major toxicities were
      grade 4 diarrhea occurring in two patients and grade 3 mucositis occurring in
      five patients. There was minimal myelosuppression (grade 3 thrombocytopenia in
      one patient) and no occurrences of hand-foot syndrome or cardiotoxicity.
      CONCLUSIONS: This regimen demonstrates modest activity with acceptable toxicity
      in colorectal cancer patients who have failed a single-bolus FU/LV regimen.
      Modifications of this and other infusional FU-based chemotherapy regimens should
      be explored as potential salvage chemotherapy regimens in advanced colorectal
      cancer.

PMID- 7828127
TI  - A national population-based study of incidence of colorectal cancer and age.
      Implications for screening in older Americans.
AB  - BACKGROUND: Population-based screening programs with flexible sigmoidoscopy have
      been advocated as a means to reduce the death rate from colorectal cancer.
      Because other studies have suggested a greater prevalence of lesions inaccessible
      to sigmoidoscopy in older patients, the expected yield of this procedure may
      differ in these subgroups. METHODS: A 100% sample of Medicare beneficiaries 65
      years or older with a first known diagnosis of colorectal cancer in 1987 was
      studied. Tumor site was divided into rectum, distal colon (distal to splenic
      flexure) and proximal colon. The analysis was also stratified by sex, race, and
      presence or absence metastatic disease, and incidence rates at each site by 5
      year age group were calculated. RESULTS: Among the 75,266 patients studied, the
      incidence of colorectal cancer increased from 1.59 patients/1000 in patients age
      65-69 years to 3.87 patients/1000 in patients age 85 years and older. Although
      the incidence rates at all three sites increased, the increment was greatest for
      proximal tumors. The incidence trends with age also persisted in an analysis of
      only metastatic lesions. Moreover, incidence rates were consistently higher in
      men than in women and higher in whites than in blacks at all sites, though the
      age-related increase in incidence was consistent among all four groups.
      CONCLUSIONS: The proportion of tumors beyond the reach of sigmoidoscopy increased
      with age, as did the actual incidence of accessible lesions. These patterns were
      also consistent in subgroup analyses. As the age-related increase in incidence
      was observed for metastatic tumors at all sites in the colon, age-related
      differences in screening and diagnostic evaluation alone do not adequately
      explain the findings. These data underscore the need for further studies of the
      relative benefits of cancer screening and pathogenic factors in tumor development
      in different subgroups of the older population.

PMID- 7828128
TI  - A fixed-ratio combination of uracil and Ftorafur (UFT) with low dose leucovorin.
      An active oral regimen for advanced colorectal cancer.
AB  - BACKGROUND: UFT is a fixed-ratio combination of uracil and Ftorafur, a prodrug
      that is absorbed orally and metabolized in vivo to 5-fluorouracil (5-FU). Uracil
      potentiates 5-FU through interference with its catabolism. The combination of UFT
      and leucovorin in patients with advanced incurable colorectal cancer, to evaluate
      preliminary activity and toxicity in this patient population. METHODS: Twenty-one
      patients were treated. Twenty patients were evaluable for toxicity and response.
      Patients received UFT 350 mg/m2/day divided every 8 hours. Patients took a 5 mg
      tablet of leucovorin every 8 hours, concurrent with each UFT dose. Treatment was
      continued for 28 consecutive days, followed by a 7-day rest. RESULTS: Five major
      objective responses (one complete and four partial) were observed. Toxicity was
      mild, with no dose-limiting myelosuppression. Four patients experienced grade 3
      diarrhea or higher, and two patients experienced dose-limiting mucositis.
      CONCLUSION: UFT and low dose leucovorin is a well tolerated, orally administered
      regimen with activity in colorectal cancer. A randomized comparison of this
      regimen with conventional parenteral regimens is warranted.

PMID- 7828129
TI  - Conservative versus nonconservative treatment of epidermoid carcinoma of the anal
      canal for tumors longer than or equal to 5 centimeters. A retrospective
      comparison.
AB  - BACKGROUND: The role of radiotherapy alone in the sterilization of anal canal
      epidermoid carcinomas of 5 cm or more remains to be assessed. Thus, the outcomes
      of patients treated with radiotherapy alone (RT) versus those treated with
      preoperative radiotherapy and surgery (RS) were compared retrospectively.
      METHODS: Between 1972 and 1990, 185 patients were treated with curative intent
      either with RT alone (n = 147) or with RS (n = 38). The Mean tumor length was
      6.18 +/- 1.14 cm and was significantly longer in the RS group (6.55 +/- 1.29 cm)
      than in the RT group (6.08 +/- 1.08 cm) (P = 0.02). The median follow-up was 77
      +/- 57 months and 93 +/- 60 months (P = 0.23) for the RT and RS groups,
      respectively. For the RT group, the first course of radiotherapy was 40 to 45 Gy
      in the pelvis for 4 to 5 weeks; after a rest of 4 to 6 weeks, radiotherapy was
      boosted an additional 15 to 20 Gy for 2 weeks. The RS patients received 40 to 45
      Gy in the pelvis for 4 to 5 weeks, then received surgery after a median period of
      54 days. RESULTS: The overall 10-year cancer specific survival rates were 58% in
      the RT group and 66% in the RS group (P = 0.48). The T-stage 10-year cancer
      specific survival rates were 68% in the RT group and 67% in the RS group for T2
      tumors (P = 0.96); 57% in the RT group and 53% in the RS group for T3 tumors (P =
      0.85); and 42% in the RT group and 40% in the RS group for T4 tumors (P = 0.05).
      In the RS group, the local control rate was 75% (3/4) for T2 tumors; 74% (17/23)
      for T3 tumors; and 82% (9/11) for T4 tumors. In the RT group, the local control
      rate was 77% (34/44) for T2 tumors; 70% (58/82) for T3 tumors; and 60% (12/20)
      for T4 tumors. In the RT group, the anal conservation rate was 61% (27/44) for T2
      tumors, 59% (48/82) for T3 tumors, and 55% (11/20) for T4 tumors. Local tumoral
      control and a functioning anus were present in 72 out of 147 (49%) patients [52%
      (23/44) for T2 patients, 52% (43/82) for T3 tumors, and 30% (6/20) for T4
      patients]. In the RS group, the grade 3 complication rate was 9% (13/146) and in
      the RS group, 5% (2/38). CONCLUSION: For patients with T4 tumors, preoperative
      radiotherapy and surgery seemed to be better in terms of survival and local tumor
      control rate, but the difference was not significant probably because the number
      of patients in the RS group was small. For these large tumors, the treatment
      should probably be more aggressive, combining chemotherapy and radiation therapy,
      but the increase of local control in relation with the addition of cytotoxic
      chemotherapy to irradiation is not proved.

PMID- 7828130
TI  - Clinical relevance of Ki-67 expression in bone tumors.
AB  - BACKGROUND: The availability of Ki-67 monoclonal antibody has opened new
      possibilities for an extensive analysis of cell kinetics in human neoplasms. Ki
      67 antibody reveals a nuclear antigen that is expressed in proliferating but not
      in quiescent cells. Although the reliability of Ki-67 immunostaining has been
      evaluated in different tumor types, little information has been reported on bone
      neoplasms. METHODS: Cell proliferation, as determined by Ki-67 expression, was
      measured by immunofluorescence on representative cytospins obtained from 205
      patients with bone tumors. In each sample, the percentage of Ki-67-positive cells
      was quantified on at least 500 cells and expressed as Ki-67 labeling index (LI).
      RESULTS: Ki-67 LI was lower in benign and low grade lesions as compared with high
      grade malignant lesions. A correlation between Ki-67 LI and histologic grade was
      observed in osteosarcoma and chondrosarcoma. In osteosarcoma, among the 43
      primary lesions included in this study, 30 patients, all treated with the same
      regimen of chemotherapy and limb-salvage surgery, were selected to establish the
      prognostic significance of cell proliferation. The Ki-67 labeling was higher in
      patients with a good histologic response to chemotherapy. However, at a 24-month
      follow-up, a worse prognosis was associated with a higher proliferative activity,
      whereas no correspondence was found between the histologic response to
      preoperative chemotherapy and the disease free survival, suggesting that in high
      grade osteosarcoma the biologic aggressiveness expressed by high levels of Ki-67
      LI may be clinically more relevant than the responsiveness to antineoplastic
      agents. CONCLUSIONS: In bone tumors, the level of Ki-67 expression correlates
      with the level of malignancy and is diagnostically and prognostically useful.

PMID- 7828131
TI  - A phase III randomized study of oral verapamil as a chemosensitizer to reverse
      drug resistance in patients with refractory myeloma. A Southwest Oncology Group
      study.
AB  - BACKGROUND: Multiple myeloma is considered to be a drug responsive disease;
      however, there is no cure for this disease and virtually all patients will
      develop drug resistance. One form of drug resistance that has been documented is
      the multidrug resistance phenotype or MDR. METHODS: A randomized trial of the
      combination of vincristine, doxorubicin, and dexamethasone (VAD) and VAD plus
      oral verapamil (VAD/v) in drug refractory multiple myeloma patients was performed
      by the Southwestern Oncology Group. Verapamil was used as a chemosensitizing
      agent to attempt to overcome or prevent MDR and improve the therapeutic outcome.
      RESULTS: Response rates between the two treatment arms were similar with an
      overall response rate of 41% for the VAD alone arm and 36% for the VAD/v arm.
      Overall survival of patients was also similar with a median survival of 10 months
      for the VAD arm and 13 months for the VAD/v arm. The toxicity profile was also
      similar for both treatments, with myelosuppression being the dose-limiting
      toxicity. No significant correlation was observed between expression of P
      glycoprotein, serum verapamil levels, and response to therapy. CONCLUSIONS: No
      beneficial effect was observed from the addition of oral verapamil to the VAD
      chemotherapy regimen for the treatment of drug-resistant myeloma patients. More
      effective and less toxic chemosensitizers are needed to study the role of
      chemosensitizers in reversing MDR in the clinic.

PMID- 7828132
TI  - Use of the polymerase chain reaction in the detection of AML1/ETO fusion
      transcript in t(8;21).
AB  - BACKGROUND: t(8;21)(q22;q22), found in acute myeloid leukemia (AML) and
      occasionally in myelodysplasia (MDS), results in the fusion of the AML1 gene on
      22q22 to the ETO gene on 8q22, generating a chimeric AML1/ETO transcript, which
      is a molecular marker of the translocation. METHODS: Reverse transcription
      polymerase chain reaction (RT-PCR), with two pairs of nested AML1 and ETO
      primers, was used to amplify the AML1/ETO fusion transcript. The Kasumi-1 cell
      line was used as a positive control. RESULTS: RT-PCR has a sensitivity of 0.0001%
      (10(-6)), corresponding to detection of 0.5 picograms of leukemic RNA in the
      presence of 0.5 micrograms of normal RNA. Using this approach, patients with
      t(8;21) (three patients with de novo AML, one with therapy-related AML, and one
      patient with myelodysplasia) yielded the same 222 base pair PCR product,
      suggesting that the breakpoints occurred at the same AML1 and ETO introns as
      previously reported. Three patients were still PCR-positive when in complete
      remission after chemotherapy and two experienced relapse. However, in another
      three patients with t(8;21) who were in remission for 2 months, 2 years, and 3
      1/2 years, respectively, PCR was negative. CONCLUSION: RT-PCR is a sensitive
      method of detection of t(8;21), and is useful in the monitoring of minimal
      residual leukemia. As the junction of AML1/ETO appears to be constant, RT-PCR may
      offer a quick and accurate diagnosis of t(8;21).

PMID- 7828133
TI  - Alternating chemotherapy regimens for patients with metastatic breast cancer. A
      pilot study based on tumor marker kinetics. Cancer and Leukemia Group B.
AB  - BACKGROUND: Chemotherapy is most effective when applied during the biologically
      active stage of tumor cells. According to the authors' previous tumor marker
      kinetic study, methotrexate plus 5-fluorouracil (MF) was found to yield either a
      cytolytic effect in an MF-sensitive tumor cell population or a cytostatic effect
      in an MF-resistant population. In the latter, the suppressive effect was
      transient and the biologic activity resumed in one week after MF administration.
      METHODS: Based on this marker kinetic study, an alternating chemotherapy program
      was designed to study its antitumor and side effects. Methotrexate (M) (200
      mg/m2) and 5-fluorouracil (F) (500 mg/m2) were administered intravenously on day
      1 followed 24 hours later by leucovorin (L) (10 mg/m2 orally every 6 hours for 6
      doses). Cyclophosphamide (C) 300 (mg/m2), doxorubicin (A) (50 mg/m2), and
      vincristine (V) (1 mg/m2) were given on day 8. The MFL/CAV was given every 4
      weeks. RESULTS: Forty-nine patients with metastatic breast cancer were enrolled;
      41 were eligible. There were 5 complete and 23 partial remissions, producing a
      total response rate of 68%. In 15 patients with liver metastases, the response
      rate was 73% and the median survival 13.7 months, results superior to those
      previously reported for this subgroup of patients. Side effects were manageable.
      CONCLUSIONS: This regimen, which can be given safely in an outpatient setting,
      yielded encouraging response and survival rates in patients with visceral
      dominant disease with poor prognoses.

PMID- 7828134
TI  - Phase II trial of an all-oral regimen of tegafur and folinic acid in patients
      with previously treated metastatic breast cancer.
AB  - BACKGROUND: Tegafur is an antimetabolite slowly metabolized to 5-fluorouracil in
      vivo. Protracted administration of oral tegafur is active in metastatic breast
      cancer, with reported response rates ranging from 29 to 44%. The addition of
      folinic acid could improve the efficacy of tegafur by means of biochemical
      modulation. METHODS: A prospective Phase II trial in patients with pretreated
      metastatic breast cancer was performed. The regimen consisted of oral tegafur
      (750 mg/m2/day) and oral folinic acid (45 mg/day) for 21 days, recycling at day
      28. RESULTS: Twenty-five patients were included. Eight partial responses were
      observed for an objective response rate of 32% (95% confidence intervals for
      response, 23-41%). The median duration of response was 7 months. According to WHO
      criteria, 24% of patients experienced grade 3 mucositis and 12% grade 3 diarrhea,
      but no other significant toxicities were observed. Twenty-eight percent of
      patients required dose reductions for toxicity. CONCLUSIONS: A significant
      response rate with oral tegafur and folinic acid in patients with heavily
      pretreated breast cancer was found. This all-oral regimen, which could be safely
      administered on an outpatient basis, deserves further evaluation to define the
      role of folinic acid on the activity of tegafur in metastatic breast cancer.

PMID- 7828135
TI  - Ureteral stricture as a late complication of radiotherapy for stage IB carcinoma
      of the uterine cervix.
AB  - BACKGROUND: Ureteral stricture is a rare late complication of curative
      radiotherapy for carcinoma of the cervix. A retrospective study was performed to
      determine the incidence and latency of radiation-induced ureteral stricture, to
      investigate possible contributing factors, and to compare the time course and
      presenting characteristics of ureteral compromise caused by late radiation injury
      or tumor recurrence. METHODS: The records of 1784 patients with FIGO stage IB
      carcinoma of the cervix treated with radiotherapy at The University of Texas M.
      D. Anderson Cancer Center between 1960 and 1989 were reviewed. The
      characteristics of patients who developed ureteral stricture as a first
      manifestation of recurrent disease or without evidence of pelvic recurrence were
      compared. The risk of ureteral compromise was calculated actuarially. RESULTS:
      There were 29 patients with severe radiation-induced ureteral stricture. The
      overall incidences of severe ureteral stenosis were 1.0, 1.2, 2.2, and 2.5% at 5,
      10, 15, and 20 years, respectively, reflecting a continuous actuarial risk
      increase of approximately 0.15% per year. Four patients died of complications
      from bilateral ureteral stricture. Patients who were treated with centrally
      blocked external fields or who received more than two transvaginal radiation
      treatments were at increased risk for developing ureteral stenosis. The risk was
      similar for patients treated with radiation alone or followed by extrafascial
      hysterectomy. CONCLUSIONS: During the first 5 years after treatment, tumor
      recurrence is the most common cause of ureteral stricture in patients treated
      with radiotherapy for carcinoma of the cervix. However, radiation injury to the
      ureter, although rare, may not become apparent for many years, necessitating
      continued vigilance throughout the lives of these patients.

PMID- 7828136
TI  - Immunohistochemical assessment of tumor proliferation and volume of embryonal
      carcinoma identify patients with clinical stage A nonseminomatous testicular germ
      cell tumor at low risk for occult metastasis.
AB  - BACKGROUND: Thirty percent of patients with clinical Stage A nonseminomatous
      testicular germ cell tumor (NSGCT) are incorrectly clinically staged. In a
      previous retrospective study at Indiana University, the combination of tumor
      proliferation rates by flow cytometry and histopathologic evaluation defined risk
      groups for occult metastatic disease in these patients with clinical Stage A
      NSGCT: A new immunohistochemical proliferation marker (MIB-1) was therefore used
      to assess growth fraction in combination with histopathology in an effort to
      predict pathologic stage in patients with clinical Stage A NSGCT: METHODS:
      Primary orchiectomy specimens from 90 consecutive patients with clinical Stage A
      NSGCT (January 1992-November 1993) who underwent retroperitoneal lymph node
      dissection at Indiana University were histopathologically evaluated. Formalin
      fixed, paraffin embedded tissue sections were immunohistochemically stained using
      a monoclonal antibody against the nuclear proliferation-associated antigen Ki-67
      (MIB-1). Satisfactory staining was obtained by using an antigen retrieval method
      based on microwave oven heating of paraffin sections. RESULTS: MIB-1
      immunohistochemical staining showed significant differences in mean values
      between 65 patients (66.1%) with pathologic Stage A NSGCT and 25 (80.4%) patients
      with pathologic Stage B NSGCT (P = 0.0032). The negative predictive value for
      patients with pathologic Stage A disease was 87% using a cut-off of 80% or less
      MIB-1 positively stained cells. A combined approach, using the absolute volume of
      embryonal carcinoma per patient (< 2 ml) and MIB-1 immunostaining (< or = 80%)
      was able to define a group of 30% of all patients who were at extremely low risk
      for occult metastatic disease. CONCLUSIONS: MIB-1 immunostaining in combination
      with histopathology aided in defining a low risk group patients with clinical
      Stage A NSGCT but failed to identify patients at high risk for metastasis. The
      risk factors need to be tested in a prospective clinical trial to determine if
      they are potentially useful in assigning therapy to individual patients.

PMID- 7828137
TI  - Correlation of ganglioside patterns of primary brain tumors with survival.
AB  - BACKGROUND: Classification/grading schemes for brain tumors are based mainly on
      histologic examinations, but these have major limitations, which has led to a
      search for more objective prognostic markers. Gangliosides have several biologic
      effects relevant to tumors, and ganglioside compositions of primary brain tumors
      correlate with diagnosis. This led to the authors' hypothesis that ganglioside
      patterns of brain tumors might be useful as prognostic indicators. METHODS:
      Gangliosides in primary brain tumors of different histologic types from 84
      patients were analyzed. Specific ganglioside patterns and several other relevant
      variables were examined for associations with survival using a Cox proportional
      hazards model. Kaplan-Meier survival curves were analyzed using the log-rank
      test. RESULTS: Patients in whom less than 30% of total tumor gangliosides
      consisted of 1b pathway gangliosides (GD1b, GT1b, and GQ1b) had significantly
      higher risk ratios than those with more than 30% 1b gangliosides (P approximately
      0.03). The presence of 6'-LM1 (NeuAc alpha 2-->6Gal beta 1-->4Glc-NAc beta 1-
      >3Gal beta 1-->4Glc beta 1-->1Cer was also associated with a higher risk ratio (P
      approximately 0.007). Combinations of 1b gangliosides and 6'-LM1 identified three
      groups of patients regardless of histologic diagnosis. Group A, with less than
      30% 1b and the presence of 6'-LM1, had a median survival time of 331 days. Group
      B, with less than 30% 1b but no 6'-LM1, had a median survival time of more than
      698 days. Group C, with more than 30% 1b had a median survival time of more than
      776 days. CONCLUSIONS: The correlation of ganglioside patterns with survival in
      this initial investigation suggests the potential of 1b gangliosides and 6'-LM1
      to be used as prognostic indicators. Continuing research is being conducted to
      assess this possibility prospectively.

PMID- 7828138
TI  - Neuroendocrine differentiation of adrenocortical tumors.
AB  - BACKGROUND: The syndrome of multiple endocrine neoplasia type 1 frequently
      involves the adrenal cortex. The relationship between the diffuse neuroendocrine
      system and the adrenal cortex is not clear however, particularly as the adrenal
      cortex is not considered to be an intrinsic part of the diffuse neuroendocrine
      system. METHODS: The possible relationship between the adrenal cortex and the
      diffuse neuroendocrine system was investigated in a study of the
      immunohistochemical characteristics of ten normal adrenal glands, four adrenal
      adenomas, and 18 adrenocortical carcinomas using the indirect peroxidase method
      of staining intermediate filaments and neuroendocrine proteins. RESULTS: With
      synaptophysin, NSE, and vimentin there was focal staining in only few zona
      glomerulosa cells in the normal adrenal cortex, whereas adrenocortical carcinomas
      and adenomas were extensively positive for these proteins. Keratin
      immunoreactivity, present in 100% of the normal cortices, was demonstrable in
      only half of the carcinomas and absent in all adenomas. CONCLUSIONS:
      Adrenocortical tumors may originate from neuroendocrine foci. The findings
      illuminate the pathogenesis of adrenocortical carcinoma, and may carry
      significant implications about the choice of treatment of patients with this
      malignancy and other related tumors.

PMID- 7828139
TI  - High dose chemotherapy with ifosfamide, carboplatin, and etoposide combined with
      autologous bone marrow transplantation for the treatment of poor-prognosis germ
      cell tumors and metastatic trophoblastic disease in adults.
AB  - BACKGROUND: A Phase I-II trial to assess the toxicity and efficacy of a tandem
      high dose chemotherapy combining ifosfamide, carboplatin, and etoposide in germ
      cell tumors and metastatic trophoblastic disease was performed. METHODS: Thirty
      nine patients, with a total of 22 testicular tumors, 9 extragonadal germ cell
      tumors, 3 ovarian germ cell tumors, and 5 cases of metastatic trophoblastic
      disease, received tandem high dose therapy combining ifosfamide (7500-12,500
      mg/m2), carboplatin (875-1225 mg/m2), and etoposide (1000-1250 mg/m2), followed
      by bone marrow reinfusion. Among the 39 patients, 33 were refractory to cisplatin
      or carboplatin-based regimen and the response of 37 could be evaluated; 69
      cycles of this tandem high dose therapy were administered. RESULTS: The overall
      response rate was 46%, including a complete response (CR) rate of 35%. Of 21
      patients with testicular tumors who could be evaluated, 10 (47%) achieved a CR.
      No CRs were obtained in patients with refractory extragonadal germ cell tumors.
      Nine partial responders after the first cycle became complete responders after
      the second. Nine (23%) of the patients were long term survivors (> 18 months), 7
      of them in continuous CR. Side effects primarily were renal toxicity and
      enterocolitis. Seven patients (18%) died of therapy-related be explored and the
      maximum tolerated doses of this three-drug regimen remain to be determined.
      CONCLUSION: This tandem therapeutic regimen is able to overcome resistance to a
      platinum-based regimen in highly refractory germ cell tumors and gestational
      trophoblastic disease and to cure a number of patients.

PMID- 7828140
TI  - Polymorphic reticulosis is a neoplasm of large granular lymphocytes with CD3+
      phenotype.
AB  - BACKGROUND: Polymorphic reticulosis, a type of lethal midline granuloma (LMG),
      has been referred to as nasal T-cell lymphoma (NTL) because of its proliferating
      cells' positive reactivity to anti-T-lymphocyte antibodies. Recently, several
      studies have suggested that proliferating cells in NTL may be natural killer (NK)
      in nature. NK cells and human nonmajor histocompatibility-restricted cytotoxic T
      lymphocytes have the morphology of large granular lymphocytes (LGL) (i.e., a high
      cytoplasmic:nuclear ratio and cytoplasmic granules). Whether NTL-LMG possesses an
      LGL morphology is examined in this study. METHODS: Two lymph node smears,
      peripheral blood showing a leukemic picture, and an electron microscope (EM)
      examination of a cutaneous lesion, respectively, were obtained from four patients
      with NTL-LMG. Immunohistochemical examination of the proliferating cells and of
      the Epstein-Barr virus (EBV) genome by both polymerase chain reaction and in situ
      hybridization also were performed. RESULTS: All patients presented with necrotic
      and granulomatous lesions in the upper respiratory tract. Histology showed
      polymorphous cellular infiltrates containing large atypical cells with positive
      reaction to CD3 (three patients), CD43 (two patients), CD45RO (two patients), and
      OPD4 (one patient). Imprint smears revealed azurophilic large membrane-delimited
      granules in an ample cytoplasm, which was confirmed by EM. The presence of the
      EBV genome in the tumor cells was observed in one patient. CONCLUSION: The
      current findings showed that NTL-LMG or polymorphic reticulosis is a
      proliferation of LGL with a CD3+ phenotype.

PMID- 7828141
TI  - The role of radiation therapy in the multidisciplinary management of recurrent
      and metastatic breast cancer.

PMID- 7828142
TI  - Cytogenetics of tumors of soft tissue and bone. Implication for pathology.
AB  - Pathologists should be aware of the existence of diagnostically useful
      chromosomal rearrangements in several soft tissue and bone tumors. They include
      rearrangement of 8q12 in lipoblastomas, ring chromosomes in atypical lipomas,
      ring and giant marker chromosomes in well differentiated liposarcomas,
      t(12;16)(q13;p11) in myxoid liposarcomas, rearrangement of 7p21-22 in low-grade
      endometrial stromal sarcomas, t(2;13)(q37;q14) in alveolar rhabdomyosarcomas,
      t(X;18)(p11.2;q11.2) in synovial sarcomas, t(12;22) (q13;q13) in clear cell
      sarcomas, t(11;22)(q24;q12) in Ewing's sarcomas and peripheral neuroepitheliomas,
      and t(9;22)(q21-31;q11-12) in extraskeletal myxoid chondrosarcomas.

PMID- 7828143
TI  - Cytogenetic intratumor heterogeneity in soft tissue tumors.
AB  - Multiple (two to seven) samples, obtained from the same surgical specimen or at
      different occasions, were analyzed in 54 benign and malignant soft tissue tumors,
      to investigate cytogenetic clonal evolution. In 28 tumors only normal karyotypes
      were found. Ten tumors had abnormal karyotypes, but were noninformative, most
      often due to a high level of karyotypic complexity or great cell-to-cell
      variation. Sixteen tumors were informative: four (leiomyosarcoma, liposarcoma,
      malignant Schwannoma, and a benign mesenchymal tumor, probably leiomyoma) had
      identical karyotypes in different samples, whereas the remaining 12 tumors (seven
      malignant fibrous histiocytomas [MFH], two leiomyosarcomas, two liposarcomas, and
      one synovial sarcoma) displayed intersample heterogeneity. Also, intrasample
      heterogeneity was detected; more than one clone was found in 21 of 73 samples
      with aberrations from 26 tumors. The different clones were related in all cases
      except two. In seven cases, samples from different occasions were studied, and
      clonal evolution could be evidenced in five of them, whereas in two cases the
      karyotypes remained unchanged. The results indicate that the acquisition of ring
      chromosomes is an early event in the development of MFH and possibly also
      pleomorphic liposarcoma. The findings, together with previous data, also indicate
      that rearrangements of 19p13 are late events in the progression of pleomorphic
      sarcomas. The overall conclusion from this study is that cytogenetic
      heterogeneity is common in soft tissue tumors, and that this might influence the
      evaluation of cytogenetic and molecular genetic findings.

PMID- 7828144
TI  - Cytogenetic analysis of soft tissue sarcomas. Recurrent chromosome abnormalities
      in malignant peripheral nerve sheath tumors (MPNST).
AB  - Malignant peripheral nerve sheath tumors (MPNST) are known to develop in patients
      with neurofibromatosis 1 (NF1), thus providing an excellent model for the study
      of multistep carcinogenesis in genetically predisposed individuals. To determine
      the sites of gene(s) involved in such a process, we have performed cytogenetic
      analysis on 10 tumors. The patients were five males and five females ranging in
      age from 15 to 77 years. Nine patients had NF1. Karyotypic analysis of these
      tumors exhibited complex clonal abnormalities of several chromosomes. Recurrent
      abnormalities (numerical as well as structural) of chromosomes 1, 11, 12, 14, 17,
      and 22 occurred in a substantial proportion of tumors studied. Although
      abnormalities of these chromosomes have been seen in a variety of other tumors,
      the aberrations of chromosomes 17 and 22 are of particular interest; chromosomes
      17 and 22 carry the genes for NF1 and NF2, respectively. In addition to other
      clonal aberrations, six tumors had abnormalities of both chromosomes 17 and 22,
      while three tumors only had an abnormality of chromosome 17. In eight tumors a
      structural abnormality of chromosome 17 included deletion or a relative
      deficiency of 17p; in four of the tumors there was also either deletion or
      rearrangement of the NF1 locus at the cytogenetic level. One tumor had monosomy
      of chromosome 17. The abnormality of chromosome 22 was deletion of 22q11.2-
      >qter. This study suggests that the germline mutation in one of the copies
      accompanied by loss or inactivation of the second copy of the NF1 gene and tumor
      suppressor gene(s) on 17p and 22q may be associated with the neoplastic
      transformation; abnormalities of other chromosomes may be related to progression
      of MPNST. Although the role of the p53 gene in carcinogenesis is well documented
      in several tumor types, the role of the NF2 gene or other unidentified tumor
      suppressor gene(s) on chromosomes 22q, 1p, 11, 12, 14 remains to be seen.

PMID- 7828145
TI  - Amplification of chromosome subregion 12p11.2-p12.1 in a metastasis of an i(12p)
      negative seminoma: relationship to tumor progression?
AB  - Cytogenetic analysis of a metastasis of a human testicular germ cell tumor
      (seminoma) revealed multiple numerical and structural anomalies, including an
      abnormally banding region (ABR) present on the short arm of one of the chromosome
      12 homologs. Fluorescence in situ- and comparative genomic hybridization
      experiments revealed that the ABR results from the amplification of 12p11.2-p12.1
      derived sequences. We speculate that this particular region may harbor gene(s)
      relevant for testicular germ cell tumor progression.

PMID- 7828146
TI  - Complex translocations of the Ph chromosome and Ph negative CML arise from
      similar mechanisms, as evidenced by FISH analysis.
AB  - The authors report on 13 patients with chronic myeloid leukemia (CML) studied by
      serial karyotyping and fluorescence in situ hybridization (FISH) of their bone
      marrow cells. Ten patients had complex translocations of the Ph chromosome while
      the remaining three were Ph negative. FISH analysis revealed in all 13 patients
      the translocation of the ABL protooncogene into chromosome 22 at band q11.
      Moreover, in all complex translocations but one, FISH with a chromosome 22
      painting probe demonstrated on one chromosome 9 at band q34 the presence of
      material from chromosome 22, in addition to signals on the third chromosome
      involved in complex changes. Therefore, in this study complex translocations
      appeared as secondary changes resulting from two consecutive translocations with
      a total of at least four breaks. The first translocation gave rise to the
      standard t(9;22)(q34;q11). The second one included a break distal to the original
      breakpoint at band 9q34 and another one on a third chromosome. Furthermore FISH
      using S1 and S15 probes, mapped at band 22q11.2 or 22q12, gave evidence that in
      complex translocations the secondary breakpoint on der(9) was in the translocated
      segment 22q11-qter between bands q11 and q12. FISH analysis also disclosed the
      presence of material from chromosome 22 on one chromosome 9 in the three patients
      with Ph negative CML, demonstrating that in these cases a retranslocation between
      chromosomes 9q+ and 22q- had occurred. Consequently, the four-break mechanism
      could also be invoked for the three Ph negative CML patients.

PMID- 7828147
TI  - Chromosomal disorder and neoplastic diseases in a family with inherited fragile
      16. Causality or casualty?
AB  - We describe a family with an inherited fragile chromosome 16 with the concurrence
      of a constitutional chromosome abnormality, together with neoplastic pathology
      within the family. The following findings should be pointed out: in relation to
      the constitutional chromosome pathology, of the proband's 3 children, the eldest
      daughter was a carrier of the fragile 16, the same as the father, and the second
      child, a son, had Down syndrome (trisomy 21). Regarding the tumoral pathology of
      this family, one of the proband's daughters died in childhood from acute
      lymphoblastic leukemia, whereas the proband developed two different malignant
      hematologic disorders: a follicular lymphoma and an acute nonlymphocytic leukemia
      (M5 type). Moreover, two independent acquired chromosome disorders coexisted in
      the proband; each of these was related to one of the respective hematologic
      disorders.

PMID- 7828148
TI  - The protooncogene CHOP/GADD153, involved in growth arrest and DNA damage
      response, is amplified in a subset of human sarcomas.
AB  - The C/EBP-homologous transcription factor CHOP (GADD153) is inducible by growth
      inhibition or DNA damage, and has been shown to be oncogenically activated by the
      specific (12;16) translocation in human myxoid liposarcoma. We have now found
      CHOP amplification in two sarcoma cell lines with previously reported
      amplification of the nearby GLI gene. Among 98 other human sarcomas of various
      types, CHOP was amplified in a hemangiopericytoma, a liposarcoma, and two
      osteosarcoma. High constitutive expression levels of CHOP were observed in tumors
      with gene amplification, but also in some other samples. The nearby MDM2 gene,
      which codes for a protein that may inactivate wild-type p53, has previously been
      reported to be frequently amplified in sarcoma. In our sarcoma panel, MDM2 was
      amplified in 9 cases. MDM2 and CHOP were co-amplified in two of these, whereas
      the two osteosarcomas had amplified CHOP but not MDM2. CHOP was amplified in both
      cell lines with GLI amplification, and MDM2 only in one. No mutations in the TP53
      gene have been found in samples with amplification of MDM2. In contrast, the cell
      line in which CHOP but not MDM2 was amplified had mutated TP53, suggesting that
      selection of this amplicon was not mediated through p53 inactivation.

PMID- 7828149
TI  - Cytogenetic studies in endometriosis tissue.
AB  - We analyzed 45 pelvic endometrial implants from 42 patients between the ages of
      14 and 40 years to investigate whether cytogenetic abnormalities were present in
      these samples. Chromosomal abnormalities have been described in benign tumors of
      the female genital tract, such as uterine leiomyomas and endometrial polyps.
      Furthermore, heritable factors have been postulated to influence a woman's
      susceptibility to develop endometrial tissue implants outside the uterine cavity.
      To study whether these factors result in or are associated with chromosomal
      changes, endometriosis cells were analyzed cytogenetically after short-term
      culture. No consistent chromosome abnormalities were observed in any of the cases
      analyzed.

PMID- 7828150
TI  - Cytogenetic and growth factor gene analysis of a renal carcinoma cell line.
AB  - Although there are many studies analyzing cytogenetic or molecular alterations of
      human renal primary tumors, there have only been a few reports addressing both
      questions on renal cell carcinoma (RCC) cell lines. We have therefore
      investigated an RCC cell line, namely KTCTL-26A, by banding techniques and
      simultaneous growth factor gene expression analysis. KTCTL-26A represents a well
      defined stemline and sidelines in the near-diploid range with clonal aberrations
      involving chromosomes 2, 3, 5, 7, 9, 13, 16, 21, 22, and Y in structure and/or
      number. The predominant karyotypic changes were a partial loss of chromosome 3p
      (ie, 3p14) and a gain of copies of chromosome 7 (trisomy or partial tetrasomy).
      By Northern analysis, in KTCTL-26A we found underexpression of the proEGF-gene
      (located on chromosome 4) and overexpression of the genes for proTGF-alpha and
      the EGF-receptor, which are located on chromosomes 2 and 7, respectively. By
      Southern blot analyses there was no evidence for an amplification in the case of
      the EGF-R and proTGF-alpha genes. Because these changes of gene expression were
      observed in both the cell line and in primary kidney tumor samples, they seem to
      be of constitutive (and not adaptive) nature. Hence, KTCTL-26A can serve as a
      model for the study of the origin of these molecular alterations and as a
      preclinical model for their genetic manipulation (e.g., by using antisense
      oligonucleotides) for therapeutic purposes.

PMID- 7828151
TI  - A factor encoded by 7q31 suppresses expansion of the 7q- clone and delays
      cytogenetic progression.
AB  - Deletion of part of chromosome 7q (7q-) is a consistent aberration in human acute
      leukemias and myelodysplasias, especially in patients with a history of genotoxic
      exposure. The deletion is usually associated with a short survival. Loss of a
      number of different 7q segments has been described, but still it is not known
      whether different deletions imply differences in survival. We have investigated
      the possible importance of loss of different segments in 77 7q- patients studied
      with high-resolution banding. Thirty-six were examined in our laboratory and 41
      were published cases. We found that when the 7q- marker contained the 7q31 band,
      the 7q- clone was smaller than when the band had been lost (p = 0.011), and the
      patients survived longer (p = 0.004). Further, karyotypes with complex
      aberrations were less frequent (p = 0.012). These results indicate that genetic
      information in 7q31 delays cytogenetic and clinical progression of myeloid
      disease with 7q-. Our results do not tell, however, whether this is due to direct
      tumor suppressor activity of a 7q31 gene or due to a more indirect effect.

PMID- 7828152
TI  - In vitro karyotype evolution and cytogenetic instability in the non-tumorigenic
      human breast epithelial cell line HMT-3522.
AB  - The "spontaneously" immortalized cell line HMT-3522, derived from a fibrocystic
      breast lesion, is used as a model for premalignant breast epithelium. During 205
      passages the cytogenetic evolution was followed. The results were compared with
      our earlier results on oncogene expression and growth factor requirements. During
      in vitro growth, gain and loss of markers, loss of normal chromosomes, and
      duplication of the chromosome complement could be demonstrated. The variability
      increased during in vitro growth. This variability, probably created randomly,
      leads to cells with different growth capacities, from which sidelines may be
      selected and become stemlines. The karyotypic evolution (including
      polyploidization) demonstrated here may be a result of genetic instability and
      heterogeneity. Although tumorigenicity was not achieved, either due to lack of
      cancer-specific gene alterations or to lack of proper selection pressure, the
      results suggest an ongoing process towards malignancy.

PMID- 7828153
TI  - Karyotypic changes in phyllodes tumors of the breast.
AB  - Cytogenetic analysis of short-term cultures of five phyllodes tumors of the
      breast-classified as benign (one tumor), borderline malignant (two tumors removed
      from the same breast in 1991 and 1993), and malignant (two tumors)--revealed
      clonal changes with simple structural abnormalities in the benign tumor, the
      borderline malignant tumors, and one malignant tumor in which benign areas and
      areas of borderline malignancy were also present. In contrast, the malignant
      tumor without admixed borderline malignant or benign areas had a complex
      karyotype. The karyotype of the benign phyllodes tumor was
      46,XX,del(12)(p11p12)/46,XX,t(8;18)(p11;p11)/46,XX. The first borderline
      malignant phyllodes tumor had t(3;20)(p21;q13) as the sole abnormality. When the
      tumor recurred, this was no longer the only clone detected and the tumor
      karyotype was now 46,XX,t(3;20)(p21;q13)/46,XX,t(9;10)(p22;q22)/46,XX,t(1;8)
      (p34;q24)/46,XX,del(11)(q22-23)/46,XX. The malignant/borderline malignant/benign
      tumor had t(1;6)(p34;p22) as the sole clonal abnormality. Finally, the karyotype
      of the malignant phyllodes tumor which contained no benign or borderline
      malignant areas was 42,XX,der(1)t(1;4)(q21;q21),der(3)t(3;17)(q29;q21), 
      4,i(8)(q10), -10, -13,i(13)(q10),der(14)t(1;14)(q21;p11),der(14)t(4;14)
      (p12;p11), -17/80-90,idemx2, +del(1)(q12), +i(1)(p10), +dic(5;5)(p14;p14),
      +i(6)(p10), +del(7)(p11), +dup(7)(q11q36), +i(15)(q10),inc/46,XX. The findings
      indicate some cytogenetic similarities between benign/borderline malignant
      phyllodes tumors and fibroadenomas of the breast, presumably reflecting similar
      pathogenetic mechanisms in the two types of mixed-lineage tumors.

PMID- 7828154
TI  - Trisomy 5 in long-term cultures from bone marrow of patients with solid tumors.
AB  - Long-term cultures of bone marrow from 15 cases diagnosed previously with primary
      solid tumors were analyzed cytogenetically. Of these cases, 10 had normal
      karyotypes and five had chromosomal abnormalities. Trisomy 5 was found in four
      cases, three with trisomy 5 as the only change and one with trisomy 5 and trisomy
      12. These results suggest that trisomy 5 may be a nonrandom change associated
      with an in vitro or in vivo phenomenon.

PMID- 7828155
TI  - Cytogenetic data in 41 patients with multiple myeloma. Karyotype and other
      clinical parameters.
AB  - Cytogenetic data of 41 patients diagnosed with multiple myeloma (MM) are
      reported. In all samples, cytogenetic studies were made of short-term and B-cell
      stimulated culture: 20 cases (48.8%) showed chromosome abnormalities; 14
      karyotypes were hypo- or pseudodiploid, and six were hyperdiploid. The most
      frequent numerical changes affected chromosomes 7, 11, 5 (gains), 14, 20, and Y
      (losses). Chromosome structural rearrangements of 22q were noted in six patients.
      Other and recurrent cytogenetic abnormalities were changes involving chromosomes
      1, 14, and 17. A significant relation was observed between presence of chromosome
      abnormalities and the following hematologic parameters: clinical stage III (p =
      0.0212), bone marrow (BM) plasma cell infiltration greater than 30% (p = 0.0379),
      presence of bone lesions (p = 0.0051), and beta 2-microglobulin levels greater
      than 4,000 md/dl (p = 0.0194).

PMID- 7828156
TI  - Pericentric inversion (2)(p15q35) in an alveolar rhabdomyosarcoma.
AB  - We report a 7-year-old girl with a pericentric inversion of chromosome 2,
      inv(2)(p15q35), in a "solid variant" of alveolar rhabdomyosarcoma. The breakpoint
      in the long arm of chromosome 2 at band q35 is, at the cytogenetic level,
      identical to the breakpoint observed in the well-established reciprocal
      t(2;13)(q35;q14) associated with the alveolar subtype of rhabdomyosarcoma. In
      this case, however, no reciprocal translocation has occurred with chromosome 13
      or any other chromosome, suggesting that the single critical breakpoint in
      alveolar rhabdomyosarcoma may be located at 2q35.

PMID- 7828157
TI  - Hematologic, clinical, and cytogenetic analysis in 109 patients with primary
      myelodysplastic syndrome. Prognostic significance of morphology and chromosome
      findings.
AB  - One hundred and nine patients with primary myelodysplastic syndrome (MDS) were
      classified according to the French-American-British (FAB) criteria: 27 refractory
      anemia (RA, 25%), 26 RA with ringed sideroblasts (RARS, 24%), 16 RA with excess
      of blasts (RAEB, 15%), 10 RAEB in transformation (RAEB-t, 9%), 25 chronic
      myelomonocytic leukemia (CMMoL, 23%), and five unclassifiable MDS (4%). Forty
      three were women and 66 were men (sex ratio 2:3). Age ranged from 30-92 years
      (mean 69 years) with nine patients aged less than 50 years (8%). A cytogenetic
      result was obtained in all cases. At initial study, a chromosome defect was
      observed in 56% of patients. Rates of abnormality depended on FAB subtype: 52% in
      RA, 100% in RA 5q-, 50% in RARS, 56% in RAEB, 70% in RAEB-t and 44% in CMMoL. The
      most frequent single defects were del(5q), -7/del(7q), del(20q), Y loss, and +8.
      Except for the 5q- syndrome entity, specific chromosome defects were not
      associated with particular FAB subtypes. Bone marrow (BM) insufficiency (22%) and
      leukemic transformation (21%) were the most important causes of death. The rate
      of leukemic transformation increased with the number of dysplastic BM cell
      lineages and was also associated with karyotype complexity and the proportion of
      abnormal/normal metaphases. The longest median survivals were observed in RARS
      (142 months) and RA/RA5q- (91 months) types. Median survivals decreased with
      increasing Bournemouth score values. Patients with three abnormal cell lineages
      had a median survival shorter than those with one or two abnormal lineages.
      Similarly, patients with complex defects had shorter survival than those with
      single or double defects or a normal karyotype. There was no statistically
      significant difference between survival of NN (normal), AN (abnormal/normal), and
      AA patients or between survival of patients with del(5q), -7/del(7q), +8 or
      del(20q).

PMID- 7828158
TI  - New discriminative chromosomal marker in adipose tissue tumors. The chromosome
      8q11-q13 region in lipoblastoma.
AB  - Specific chromosome abnormalities characterize benign and malignant adipose
      tissue tumors and are of great diagnostic and clinical importance. Lipoblastoma
      is a rare benign adipose tumor that mimics myxoid liposarcoma histologically.
      Although only a few lipoblastomas have been investigated cytogenetically, it is
      increasingly clear that these adipose tissue tumor generally show rearrangements
      of 8q11-q13 region but lack the t(12;16) that allows these tumors to be
      distinguished from myxoid liposarcomas.

PMID- 7828159
TI  - Translocation (X;8)(q2?6;q21.3) in a case of systemic mastocytosis.
AB  - Mastocytosis is a rare disease which occasionally progresses into mast cell
      leukemia or other myeloid neoplasms. Here we report on a patient with systemic
      mastocytosis who was found to have a clone with t(X;8)(q2?6;q21.3) and two copies
      of der(8)t(X;8). In accordance with these results, interphase cytogenetic
      analysis revealed that 93% of bone marrow cells contained three centromeric
      regions of chromosome 8. We suggest that the t(X;8) and the duplication of the
      translocation chromosome 8 may play a role in the progression of the diseases.

PMID- 7828160
TI  - Interstitial 9q- deletion in a case of acute myeloid leukemia-M2 arising from a
      granulocytic sarcoma.
AB  - Deletion of a portion of the long arm of chromosome 9, as the sole abnormality,
      has previously been reported in detail in 14 cases of acute myeloid leukemia
      (AML). We report on the first case of AML-M2 arising from granulocytic sarcoma
      with this chromosome abnormality as the sole karyotypic abnormality.

PMID- 7828161
TI  - On the "keimversprengungs" origin of embryonic tumors.

PMID- 7828162
TI  - CD4+ T lymphocytes infiltrating human breast cancer recognise autologous tumor in
      an MHC-class-II restricted fashion.
AB  - Tumor-infiltrating lymphocytes (TIL) were derived from primary breast tumors,
      metastatic lymph nodes and malignant pleural effusions from 34 patients with
      breast cancer. TIL were cultured for approximately 30 days and studied for
      phenotype, cytotoxicity, and the ability to secrete cytokines in response to
      autologous tumor stimulation. Tumor specimens were obtained from two different
      sites in 7 patients, resulting in 41 samples from which 38 TIL cultures were
      established. In addition to screening 38 bulk TIL cultures, TIL from 21 patients
      were separated into CD4+ and CD8+ subsets and extensively studied. Three CD4+ TIL
      were found specifically to secrete granulocyte macrophage-colony-stimulating
      factor and tumor necrosis factor alpha when stimulated by autologous tumor and
      not by a large panel of stimulators (24-34) consisting of autologous normal
      cells, allogeneic breast or melanoma tumors and EBV-B cells. This cytokine
      release was found to be MHC-class-II-restricted, as it was inhibited by the anti
      HLA-DR antibody L243. These 3 patients' EBV-B cells, when pulsed with tumor
      lysates, were unable to act as antigen-presenting cells and induce cytokine
      secretion by their respective CD4+ TIL. These findings demonstrate that MHC-class
      II-restricted CD4+ T cells recognising tumor-associated antigens can be detected
      in some breast cancer patients.

PMID- 7828163
TI  - Effect of combined administration of a synthetic low-toxicity lipid A derivative,
      DT-5461a, and indomethacin in various experimental tumor models of colon 26
      carcinoma in mice.
AB  - We investigated the antitumor effects of a synthetic lipid A derivative, DT
      5461a, in combination with indomethacin in three experimental tumor models
      (peritoneal carcinomatosis, liver tumor, and lung tumor models) of transplanted
      colon 26 carcinoma in mice. This carcinoma produces the immunosuppressive
      prostaglandin E2 (PGE2). Intravenous administration of DT-5461a alone resulted in
      little or no prolongation of survival time [increase in life span (ILS): -2%
      22%]. When indomethacin was given in drinking water a slight or moderate increase
      in survival time was seen (ILS: 4%-45%). In contrast, the combination of DT-5461a
      and indomethacin induced an additive increase in life span (ILS: 16% to more than
      193%). The strongest antitumor effect of this combined therapy was seen in the
      peritoneal carcinomatosis model; in this model, plasma PGE2 concentrations were
      considerably higher than in normal mice, and concentrations were further but
      transiently increased by DT-5461a administration. Following oral indomethacin
      administration, these elevated PGE2 concentrations were reduced to the level in
      untreated normal mice. Furthermore, intratumoral tumor necrosis factor (TNF)
      activity in the group receiving the combined therapy was significantly higher
      than that in the DT-5461a-treated group. No TNF production was induced by the
      administration of indomethacin alone. These results suggest that the antitumor
      effect of DT-5461a can be enhanced by combination with indomethacin, and that the
      inhibition of PGE2 production may have a role in this antitumor effect.

PMID- 7828164
TI  - Induction of tumor-specific cytotoxic T lymphocytes and natural killer cells by
      tumor cells transfected with the interleukin-2 gene.
AB  - To study the antitumor effect of local production of interleukin-2 (IL-2) from
      tumor cells, the poorly immunogenic murine colon cancer cells, colon26, was
      transfected with murine IL-2 cDNA in a bovine papilloma virus vector. IL-2 gene
      transfectants (mIL2 + colon26) did not alter their growth rate compared with
      parental colon26 cells in vitro, but reduced their tumorigenicity in vivo.
      Immunization with mIL2 + colon26 cells could induce protective immunity against
      parental colon26 cells. Following intravenous challenges, the colonies of lung
      metastasis were also inhibited. Moreover, inoculation of mIL2 + colon26 cells
      slowed the growth of challenged renal cell carcinoma cells, RenCa.
      Intraperitoneal inoculation of IL-2 gene transfectants generated a large number
      of peritoneal exudate cells and these cells had a highly cytolytic activity
      against colon26 and YAC-1. These results suggest that inoculation with IL-2
      transfected tumor cells can stimulate not only cytotoxic T lymphocytes but also
      natural killer cells, and that these cells will act as antitumor effector cells
      in host animals.

PMID- 7828165
TI  - Minor human antibody response to a mouse and chimeric monoclonal antibody after a
      single i.v. infusion in ovarian carcinoma patients: a comparison of five assays.
AB  - The human anti-(mouse Ig) antibody (HAMA) response was measured in serum of 52
      patients suspected of having ovarian carcinoma who had received an i.v. injection
      of either the murine monoclonal antibody (mAb) OV-TL 3 F(ab')2 (n = 28, 1 mg) or
      the chimeric mouse/human mAb MOv18 (cMOv18; n = 24, 3 mg). Serum samples were
      taken before injection and 2-3 and 6-14 weeks after administration. A double
      antigen or bridging assay was developed to detect responses against both murine
      as well as chimeric antibodies. In addition, an indirect enzyme-linked
      immunosorbent assay (ELISA) as well as three commercially available assays were
      used to study antibody response against the murine antibody OV-TL 3. With both
      the double-antigen (bridging) assay and the indirect ELISA 1 of the 28 patients
      (4%) injected with murine OV-TL 3 F(ab')2 showed a HAMA reaction 6 weeks after
      injection, which was demonstrated to be a mixed anti-isotypic and anti-idiotypic
      response. None of the 24 patients injected with the chimeric MOv18 showed an anti
      chimeric antibody response. The various commercially available assays
      demonstrated conflicting results. The double-antigen- or bridging assay is a
      reliable method to detect anti-murine and anti-chimeric antibodies. The assay can
      be easily adapted for use with human antibodies. The immunogenicity of OV-TL 3
      F(ab')2 and cMOv18 in patients is low, making both antibodies candidates for
      immunotherapy.

PMID- 7828166
TI  - Antibodies to tumor necrosis factor: a component of B cell immune responses with
      a role in tumor/host interaction.
AB  - Infiltrating B lymphocytes are found within tumors, where their role and the
      antigens they recognize are poorly defined. After in vitro expansion of these
      cells, we were able to detect the production of antibodies to tumor necrosis
      factor alpha (TNF) in 13 of 17 human tumors studied. These antibodies were
      detected by both enzyme-linked immunosorbent assay and by neutralization. Anti
      TNF antibodies were not produced by resting peripheral blood B cells of normal
      subjects. However, anti-TNF antibodies were produced by B cells obtained from
      healthy individuals, after either in vivo or in vitro antigenic stimulation. This
      suggests that anti-TNF antibody production may constitute part of the overall B
      cell response to antigens. The intratumoral production of anti-TNF antibody may
      play a role in tumor/host interactions.

PMID- 7828167
TI  - Induction of an autoimmune response against syngeneic lymphoma cells by
      immunogenic 64-kDa protein isolated from normal blast cells of BALB/c mice.
AB  - Immunogenic proteins with identical molecular mass (64 kDa) were purified from a
      syngeneic spontaneous T cell leukaemia line, designated LB3, and lymphoblast
      extracts both derived from BALB/c mice. The 64-kDa protein was purified by a
      sequence of biochemical steps from cell extracts containing protease inhibitors.
      The following steps were included in the purification pathway: Sephadex G-100 gel
      filtration, anion-exchange chromatography, concanavalin A (ConA) affinity
      chromatography, and preparative gel electrophoresis. The immunogenic fraction
      isolated in each step was subjected to the next step along the purification
      pathway. The immunogenicity of the separated fractions was measured by a lymph
      node proliferation assay, which is indicative of delayed-type hypersensitivity.
      The final 64-kDa isolated protein of blast cells induced in BALB/c mice an
      efficient lymph-node proliferation response, which was detected in the regional
      lymph node after challenge with the final isolated protein of LB3 cells and vice
      versa. In addition to their identical molecular mass, both proteins were eluted
      from an anion-exchange column with the same NaCl concentration (0.57 M) and both
      expressed affinity to the ConA-Sepharose column, suggesting that they are
      glycosylated. The specificity of the immunological responses induced or elicited
      with the various isolated proteins was also shown. The implications of these
      findings are discussed.

PMID- 7828168
TI  - Impairment of lymphocyte locomotion in the tumor microenvironment and the effect
      of systemic immunotherapy with liposome-encapsulated muramyl-tripeptide
      phosphatidylethanolamine.
AB  - The ability of the lymphocytes to move through the interstitium is obligatory to
      the immune response. We previously showed that tumor-infiltrating lymphocytes
      (TIL) from human melanoma and renal cell carcinoma demonstrate a dramatic
      decrease in their spontaneous locomotion through three-dimensional collagen gel
      when compared with peripheral blood lymphocytes (PBL) and lymph node lymphocytes.
      To determine if this decrease is caused by contact with tumor cells, or mediated
      through certain diffusible factors, we examined the effects of autologous tumor
      cells on the locomotion of PBL in a model system where tumor cells were separated
      from lymphocytes by a 3-mm layer of gelled collagen. After 21-22 h incubation in
      chamber slides, locomotion distances were assessed in the presence and absence of
      tumor and normal cells. In the presence of tumor cells, PBL from 14 of 18
      patients displayed substantial (466.5 +/- 2.7 microns compared to control 568.9
      +/- 10.9 microns, P < 0.001) loss of motility. Inhibition was more prominent in
      melanoma patients than in renal cell carcinoma patients. Thus the impaired
      locomotion previously observed in TIL was at least partially due to the presence
      of tumor. The locomotion of TIL was restored in four of five melanoma patients
      treated with liposome-encapsulated muramyl-tripeptide-phosphatidylethanolamine (L
      MTP-PE). Furthermore, in six of seven examined L-MTP-PE-treated patients, an
      increase in intrinsic PBL locomotion during the first month of the therapy was
      observed. These results suggest that the environment of the tumor is not
      conducive to locomotion of advancing lymphocytes and the therapeutic intervention
      may ameliorate the loss of lymphocytic infiltration.

PMID- 7828169
TI  - Heterogeneity of murine adherent interleukin-2-activated killer cells.
      Differential effect of prostaglandin E2 and forskolin.
AB  - We have studied the relationship between cytotoxic activity, size and granularity
      of murine interleukin-2-activated adherent killer cells issued from spleen cells
      cultured with high levels of IL-2. The effects of prostaglandin E2 (PGE2) and
      forskolin upon these cells were assessed. All adherent spleen cells obtained
      after 5 days of culture were large granular lymphocytes but presented a
      heterogeneity in size and granularity. After fractionation on a discontinuous
      density Percoll gradient, four cellular subpopulations were isolated.
      Fluorescence-activated cell sorting analysis showed that cells of the lightest
      fraction (F1) were the largest, while the cells found in the heaviest fraction
      (F4) were much more granular than the cells collected in the two intermediate
      fractions (F2 and F3). The serine esterases level was higher in F4 than in
      unfractionated cells and diminished to about 40% in cells of fractions F2 and F3,
      which expressed a cytotoxic activity against YAC-1 cells higher than that in
      unfractionated cells or in F1 or F4, which presented the lowest cytotoxic
      activity. When AK cells were cultured for 48 h in the presence of either PGE2 or
      forskolin, which induce an intracellular increase of cAMP, we observed that PGE2
      (1 microM) inhibited the cytotoxic activity, but surprisingly forskolin (2
      microM) exerted a stimulating effect on the induction of cytotoxic activity.
      After fractionation on a discontinuous Percoll gradient we observed the same
      cellular distribution among PGE2 or forskolin-treated or -untreated cells, but
      PGE2 induced an increase of size and granularity. This effect of PGE2 was more
      potent on the cells collected in F4. However this variation of granularity was
      not associated with any variation in the serine esterase level. The cytotoxic
      activity of PGE2- or forskolin-treated cells did not present any significant
      variation relative to the control for cells collected in F2 and F3; on the other
      hand, forskolin-treated cells collected in F4 showed a significantly higher
      cytotoxicity than did the corresponding untreated or PGE2-treated cells.

PMID- 7828170
TI  - Theoretical analysis of calcium wave propagation based on inositol (1,4,5)
      trisphosphate (InsP3) receptor functional properties.
AB  - In the presence of inositol (1,4,5)-trisphosphate (InsP3) repetitive waves of
      elevated cytosolic free Ca2+ (Ca waves) that travel through cellular cytoplasm
      are observed. Investigation of this phenomenon stimulated the view of cellular
      cytoplasm as 'an excitable medium composed of Ca release processes (InsP3R),
      coupled by a common stimulatory signal (Ca) through diffusion' [Lechleiter JD.
      Clapham DE. (1992) Molecular mechanisms of intracellular calcium excitability in
      Xenopus laevis oocytes. Cell, 69, 283-294]. Using a kinetic model of InsP3R
      gating, an analytical expression for the amplitude of Ca wave propagating through
      this excitable medium has been obtained. The amplitude of the Ca wave is
      determined by the combination of cell-specific parameters and the functional
      properties of a single InsP3R. An analytical expression for Ca wave propagation
      velocity has been also obtained using the Luther equation for diffusion-driven
      autocatalytic reaction. Both equations provided reasonable estimations for Ca
      wave amplitude (1.3 microM free Ca) and the velocity of the wave propagation (21
      microns/s) for Ca waves in Xenopus oocytes when numerical values of parameters
      were used. The duration of refractory period has been shown to be determined
      mainly by the activity of CaATPase. Obtained results provide an insight into the
      mechanisms underlying the process of Ca wave propagation and define the
      interrelationship between different factors involved in this process. Some
      experimentally testable predictions can be done based on the analytical
      expressions obtained for Ca wave amplitude, the velocity of Ca wave propagation
      and the duration of refractory period.

PMID- 7828171
TI  - Cytosolic free calcium concentration in the mitogenic stimulation of T
      lymphocytes by anti-CD3 monoclonal antibodies.
AB  - The effects of anti-CD3 monoclonal antibodies on cytosolic free Ca2+
      concentration, [Ca2+]i, were investigated in freshly isolated lymphocytes, T cell
      lines, T clones and the leukemic T cell line Jurkat with three different
      methodologies, i.e. classical cuvette experiments, cytofluorimetry and
      videoimaging. With any technique, concentrations of anti-CD3 antibodies optimal
      for stimulation of DNA synthesis were completely ineffective at inducing early
      increases of [Ca2+]i in freshly isolated lymphocytes. At supraoptimal mitogenic
      concentrations: (i) anti-CD3 mAb induced negligible increases of [Ca2+]i when
      tested in suspensions of freshly isolated lymphocytes, but the response increased
      progressively during in vitro culturing with IL2; (ii) most, but not all, T
      clones, when tested in suspension, were responsive to these concentrations of
      anti-CD3 antibodies in terms of [Ca2+]i; (iii) using the videoimaging technique
      at the single cell level, it was demonstrated that the anti-CD3 antibodies
      induced large increases of [Ca2+]i in lymphocytes only under conditions which
      allowed adherence of the antibodies (and of the cells) to the glass surface. In
      all T cell types investigated, the [Ca2+]i increases were most often composed by
      multiple, asynchronous oscillations. The buffering of [Ca2+]i increases, obtained
      by loading the cells with membrane permeant esters of Quin-2 and Fura-2,
      inhibited anti-CD3 mAb induced DNA synthesis, but this appeared entirely
      attributable to a toxic side effect of the ester hydrolysis. The relevance of
      these data is discussed in terms of their methodological and functional
      implications for the understanding of the role of Ca2+ in mitogenic stimulation
      of T cells.

PMID- 7828172
TI  - Differential effects of carbachol on calcium entry and release in CHO cells
      expressing the m3 muscarinic receptor.
AB  - Calcium signalling was examined in CHO-k1 cells that stably express the m3
      subtype of the muscarinic receptor. The calcium indicator Fura-2 was retained in
      these cells only in the presence of probenecid (1 mM), suggesting that Fura-2
      efflux was mediated by an organic anion transporter. The addition of carbachol
      (CCh) to Fura-2 loaded cells in suspension caused a rapid transient increase in
      intracellular calcium [Ca]i followed by a smaller sustained plateau phase. The
      transient rise in [Ca]i was dose-dependent with a threshold response of 89 +/- 18
      nM above baseline with 10 nM CCh and a maximum stimulation of 734 +/- 46 nM with
      10 microM CCh. This phase was accompanied by a similar dose-dependent stimulation
      of total inositol phosphate production and was assumed to be generated by release
      from intracellular stores of the endoplasmic reticulum (ER). The sustained
      increase in [Ca]i was generated by entry from the extracellular bath since it was
      blocked by pretreatment with La3+ (1 microM) and was absent when bath calcium was
      chelated with EGTA. This phase was not dependent on CCh dose, and a stimulation
      of [Ca]i of approximately 90 nM above baseline was observed with CCh
      concentrations between 50 nM and 10 microM. With this dose range, the rate of
      Mn2+ quenching of Fura-2 at the Ca-insensitive excitation wavelength of 360 nm
      was likewise maximally stimulated. At lower CCh concentrations (10-50 nM), it was
      clear that the activation of Ca entry could not be dissociated from a threshold
      release of Ca from intracellular stores. The phorbol ester PMA, which uncouples
      the muscarinic receptor from phospholipase C, reduced the transient rise in [Ca]i
      by approximately 50% with little or no effect on Ca entry at higher CCh levels (>
      or = 1 microM). At lower CCh concentrations (< or = 100 nM) however, pretreatment
      with PMA completely blocked all Ca mobilization and supports the contention that
      Ca entry is coupled to Ca release from stores or to store depletion. The emptying
      of inositol trisphosphate-sensitive stores with thapsigargin (10 nM) stimulated
      Ca entry and also the rate of Mn2+ quenching. Store depletion by incubation in Ca
      free media likewise stimulated Mn2+ uptake without a rise in [Ca]i. Our data are
      therefore consistent with a 'capacitative' coupling model, whereby the activation
      of the plasma membrane receptor leads to an InsP3-induced change in the degree of
      filling of the ER Ca pool.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7828173
TI  - 5-Hydroxytryptamine-stimulated calcium mobilization in cultured canine tracheal
      smooth muscle cells.
AB  - 5-Hydroxytryptamine (5-HT)-induced increase of intracellular Ca2+ concentration
      ([Ca2+]i) was monitored in cultured canine tracheal smooth muscle cells (TSMCs)
      using a fluorescent Ca2+ indicator Fura-2. Stimulation of TSMCs by 5-HT produced
      an initial transient peak followed by a sustained, concentration-dependent
      elevation of [Ca2+]i. The log (EC50) values of 5-HT for the peak and sustained
      plateau responses were -7.43 and -7.60 M, respectively. 5-HT1A and 5-HT3 receptor
      antagonists, NAN-190 and metoclopramide, inhibited the 5-HT-stimulated increase
      in [Ca2+]i with pKB values of 6.3 and 6.2, respectively, indicating that the 5-HT
      receptors mediating Ca2+ signal had low affinity for these receptor antagonists.
      In contrast, 5-HT2A receptor antagonists, ketanserin and mianserin, had high
      affinity in antagonizing the changes in [Ca2+]i response to 5-HT with pKB values
      of 8.3 and 8.3, respectively. The sustained elevation of [Ca2+]i was dependent on
      the presence of extracellular Ca2+. Removal of extracellular Ca2+ by addition of
      2 mM EGTA during the sustained phase caused a rapid decline in [Ca2+]i to the
      resting level. In the absence of extracellular Ca2+, only an initial peak was
      observed which then declined to the resting level; the sustained elevation of
      [Ca2+]i could then be evoked by addition of 1.8 mM Ca2+ in the continued presence
      of 5-HT. Ca2+ influx was required for the changes of [Ca2+]i, since the Ca(2+)
      channel blockers, diltiazem, verapamil, and Ni2+, decreased both the initial and
      sustained elevation of [Ca2+]i in response to 5-HT. These Ca(2+)-channel blockers
      also decreased the sustained elevation of [Ca2+]i when applied during the plateau
      phase. In conclusion, these findings indicate that the initial increase in
      [Ca2+]i stimulated by 5-HT acting on 5-HT2A receptors is due to the release of
      Ca2+ from internal stores, followed by the influx of external Ca2+ into the
      cells. The influx of extracellular Ca2+ partially involves a diltiazem and
      verapamil sensitive Ca2+ channel.

PMID- 7828174
TI  - A UV laser-scanning confocal microscope for the measurement of intracellular
      Ca2+.
AB  - Modifications to the optics of a conventional confocal laser-scanning microscope
      were made to allow imaging intracellular Ca(2+)-dependent fluorescence with a UV
      laser (351 or 364 nm). Modifications included: (1) a chromatic compensation lens
      in the laser path; (2) the design of a practically achromatic relay lens; (3) a
      longer tube length for the objective; and (4) highly reflective mirrors
      maximizing fluorescence measurement. This UV laser-scanning confocal microscope
      (UV-CLSM) yielded a lateral resolution of < 0.3 micron and an axial resolution of
      < 1.5 microns and a relevant field size of 100 microns in diameter for a 40X
      objective). The effects of varying the focal length of a compensation lens, the
      degree of the correction for the coverglass thickness of objective and the
      detector aperture size on the quality of image formation were examined. Finally,
      UV-CLSM revealed optical sections of fine and complex structures of bullfrog
      sympathetic neurones loaded with a Ca(2+)-sensitive fluorescent probe. Changes in
      intracellular free Ca2+ distribution in response to high [K+] or caffeine were
      demonstrated. In addition, an increase in the intracellular concentration of
      caffeine applied externally was clearly imaged in space and time and
      distinguished from a resultant rise in [Ca2+]i. Thus, the UV-CLSM developed is
      suitable for ratiometric intracellular Ca2+ measurements and other biological
      studies.

PMID- 7828175
TI  - Extracellular ATP activates calcium entry and mobilization via P2U-purinoceptors
      in rat lactotrophs.
AB  - Extracellular ATP has been previously shown to activate calcium signalling in
      pituitary cell populations [1] but the particular cell types involved have not
      been identified. We used video imaging of Fura-2 loaded into single rat pituitary
      cells and identified as lactotrophs to study the effects of extracellular ATP on
      [Ca2+]i. ATP does not permeabilize the cells as shown by exclusion of propidium
      iodide. ATP causes two types of calcium transients in lactotrophs. The most
      common response is a rapid increase in [Ca2+]i that decays slowly and is
      terminated by washout of ATP. This type of response is also seen in calcium-free
      medium, demonstrating mobilization of calcium stores dependent upon the presence
      of the agonist. ATP also stimulates calcium entry as detected by Mn(2+)-quenching
      of Fura-2. ATP in Mg(2+)-free medium and ATP gamma S are effective agonists
      suggesting ATP4- is the active form. The presence of P2-purinoceptors is apparent
      because ATP, ADP and AMP increase [Ca2+]i in decreasing order of potency and
      adenosine has no effect. ATP-induced calcium transients are reduced by the P2
      purinoceptor antagonists suramin and quinidine. UTP is equipotent with ATP and
      defines the receptor subtype as P2U. We conclude that ATP4- acts on rat
      lactotrophs via P2U-purinoceptors to elevate [Ca2+]i from intracellular and
      extracellular sources.

PMID- 7828176
TI  - An evaluation of the quantity of antenatal care at rural health centres in
      Matebeleland North Province.
AB  - The study was conducted to evaluate the quality of antenatal care (ANC) provided
      at rural health centres (RHC). Matebeleland North Province in Zimbabwe was
      selected as the study area. A qualitative, descriptive study was conducted with
      the application of the modified EPI/Cluster Sampling Method for the 30 rural
      health centres selected as primary sampling units. The research methodology
      consisted of an assessment of structure and process evaluation. Antenatal care
      clients attending rural health centres were interviewed, records audited and
      process observations undertaken of health centre staff performing antenatal
      duties. An inventory and use of equipment at these facilities was conducted. The
      study indicated that there was overall consumer satisfaction with the antenatal
      care services in the province. More than 65 pc of the clients indicating that
      they were less than 10 km from a health facility that provided antenatal care. As
      expected from the facility sample of women cost recovery did not feature as a
      barrier to assess. The professional performance by health workers at rural health
      centre level in the province in the provision of antenatal care was found to be
      unsatisfactory. Limited availability of equipment coupled with poor know-how
      contributed significantly to the provision of poor services. Whereas health
      workers were able to identify some pregnancy related risk factors, inadequate
      efforts were put into minimizing their contribution to the adverse outcome of
      pregnancy. The study proposes strategies to improve the quality of antenatal care
      through organisational review and implementation of relevant policies and
      technical procedures.

PMID- 7828177
TI  - Can our people afford to live? The effect of changing economic conditions on high
      density urban dwellers around Harare, March 1992 to June 1993.
AB  - The Department of Community Medicine with the assistance of fourth year medical
      students have been monitoring the basic cost of living of high density urban
      dwellers near Harare from March 1992 to June 1993. The cheapest diet able to
      provide sufficient calories, protein and vitamin A for a standard family of five
      people was calculated, and also the average cost of rent, rates, essential travel
      and schooling for a month. Sixty to 80 people were interviewed on each of four
      occasions. The cost of basic foods increased by over 50 pc from $157.50 in March
      1992 to $349.20 in June 1993, and the cost of rents, rate, transport and
      schooling from $230.63 to $268.43 in the same period. This gave an average total
      monthly cost of $388.18 in March 1992 and $617.63 in June 1993. Minimum costs
      were calculated by using the mean cost of rent and rates etc.--2 standard errors.
      This increase in the basic cost of living is compared with the wages of security
      guards and the implications regarding the affordability of health care.

PMID- 7828178
TI  - Smoking in a poor, rapidly expanding urban community of South Africa.
AB  - Data on smoking in Alexandra (Alex) was collected during a demographic household
      survey, as part of a community survey on disability, using a cluster sampling
      methodology. Males smoked more than females, rate of smoking increased with age
      and seemed to increase with length of residence in Alex. The rate of smoking was
      higher for the informal shack dwellers (26 pc) than for either the new housing
      developments (13 pc) or old brick dwellings (17 pc). In a logistic regression
      model with age, sex, length of residence and area of residence, age was the only
      factor that remained statistically significant. The results are discussed and
      recommendations for the primary health care (PHC) level are advanced.

PMID- 7828179
TI  - Lack of difference in blood pressure between the urban and rural population in
      Lesotho, Africa.
AB  - In this preliminary study, blood pressure and associated factors were studied in
      233 urban and 194 rural Basotho's, aged 18 to 88 years. Blood pressure was shown
      to increase with age in both sexes, but no significant differences were noted
      between urban and rural men. A significant in difference diastolic BP was seen
      between urban and rural women aged 18 to 34 years, (p < 0.01), and women over 55
      years (p < 0.05) but this did not correlate with the Body Mass Index (BMI).
      Significant difference in BMI between men and women was seen in the 18 to 34
      years, 35 to 54 years age groups, (p < 0.001), and the over 55 years group (p <
      0.05). However, significant blood pressure differences between men and women were
      only seen in the 18 to 34 years group, in which men who had a lower BMI had a
      significantly higher blood pressure (p < 0.001) than women with a higher BMI.
      Prevalence of 14.9 pc rural, 12.4 pc urban hypertension was seen. This may be
      partly contributed by diet and urbanisation of rural Basothos. Further studies
      into factors contributing to hypertension should be carried out in Lesotho.

PMID- 7828180
TI  - Cytogenetics in urology.
AB  - Cytogenetic investigations throw some light into the bizarre and confusing state
      of intersexuality and disorders of sexual differentiation. Many a time,
      presentation of a patient with a totally ambiguous or mixed up external
      genitalia, lends confusion towards the assignment of sex to the individual
      patient. Even more disastrous is the assignment of the wrong sex to a patient due
      to the fact that inadequate investigations had been performed, followed by a
      hasty surgical procedure based on the inadequate investigations. With cytogenetic
      investigations, sex assignment is made slightly easier and more sensible. These
      investigations should be performed in the very early stages of life. Parents and
      sometimes patients themselves are, therefore, as a consequence, advised in a
      meaningful manner, to avoid later psychological catastrophes and hazards.
      Cytogenetic studies are therefore a prerequisite, an advantage, and imperative in
      patients with ambiguous genitalia. The experiences here involving 87 patients,
      have demonstrated that these investigations will always help to categorise the
      ambiguous genitalia patient accurately.

PMID- 7828181
TI  - Diabetic mortalities in Ilesa, Nigeria: a retrospective study.
AB  - Twenty five patients (15 males and 10 females) died out of a total of 114
      diabetics (21.9 pc) admitted over a six year period. Fourteen of them were new
      cases diagnosed for the first time on presentation. Death occurred within 72
      hours of admission for eight (57 pc) of these new cases. Among the 11 known
      diabetics who died, eight were clinic defaulters. Diabetic ketoacidosis (DKA) was
      the cause of death in eight (32 pc) of the patients studied and this proved to be
      the commonest cause of death. Results of laboratory tests for five patients were
      not available before their death and two patients with DKA could not afford the
      over the counter cost of insulin and normal saline as they were unavailable in
      the hospital pharmacy at the time of their presentation. This study clearly
      demonstrates that the risk of death among Nigerian diabetics is increased by a
      high defaulting rate and delayed diagnosis and treatment. This is further
      aggravated by the near absence of emergency laboratory services and drug
      shortages in the hospital.

PMID- 7828182
TI  - The management of diabetic ketoacidosis.

PMID- 7828183
TI  - The out of stock syndrome.

PMID- 7828184
TI  - Use of loperamide in children.

PMID- 7828185
TI  - High-dose riboflavin as a prophylactic treatment.

PMID- 7828186
TI  - High-altitude headache.

PMID- 7828187
TI  - White matter MRI hyperintensities in a hundred-and-twenty-nine consecutive
      migraine patients.

PMID- 7828188
TI  - Neuropeptides in migraine and cluster headache.
AB  - The cerebral circulation is invested by a rich network of neuropeptide Y (NPY)
      and noradrenaline containing sympathetic nerve fibers in arteries, arterioles and
      veins. However, the nerve supply of vasoactive intestinal peptide (VIP),
      substance P (SP) and calcitonin gene-related peptide (CGRP) containing fibers is
      sparse. While noradrenaline and NPY cause vasoconstriction, VIP, SP and CGRP are
      potent vasodilators. Stimulation of the trigeminal ganglion in cat and man
      elicits release of SP and CGRP. Subjects with spontaneous attacks of migraine
      show release of CGRP in parallel with headache. Cluster headache patients have
      release of CGRP and VIP during bouts. Treatment with sumatriptan aborts headache
      in migraine and cluster headache as well as the concomitant peptide release.

PMID- 7828189
TI  - High-dose riboflavin as a prophylactic treatment of migraine: results of an open
      pilot study.
AB  - If the brain of migraineurs is characterized between attacks by a reduction of
      mitochondrial phosphorylation potential, riboflavin, which has the potential of
      increasing mitochondrial energy efficiency, might have prophylactic effects in
      migraine. In this preliminary open pilot study, 49 patients suffering from
      migraine (45 without aura, 4 with aura) were treated with 400 mg of riboflavin as
      a single oral dose for at least 3 months. Twenty-three patients received in
      addition 75 mg of aspirin. Mean global improvement after therapy was 68.2% and
      there was no difference between the two groups of patients. With the exception of
      one patient in the riboflavin plus aspirin group who withdrew because of gastric
      intolerance, no drug-related side effects were reported. High-dose riboflavin
      could thus be an effective, low-cost prophylactic treatment of migraine devoid of
      short-term side effects. A placebo-controlled trial of its efficacy seems
      worthwhile.

PMID- 7828190
TI  - Oral sumatriptan: effect of a second dose, and incidence and treatment of
      headache recurrences.
AB  - Oral sumatriptan in a dose of 100 mg aborts about 60% of migraine attacks within
      2 h, but the headache may recur within 24 h. We investigated: (i) the incidence
      of headache recurrence after oral sumatriptan (ii) whether a second tablet of
      sumatriptan at 2 h increases initial efficacy and/or (iii) prevents headache
      recurrence and (iv) whether a further tablet of sumatriptan treats headache
      recurrence. In a randomized parallel-group clinical trial, 1246 patients treated
      one to three migraine attacks (with or without aura), with 100 mg oral
      sumatriptan. Two hours later they all took a double-blind randomized second table
      of sumatriptan (group I) or placebo (group II). Patients who initially improved,
      but then experienced headache recurrence took a further double-blind randomized
      tablet of sumatriptan or placebo. Proportions of patients who improved from
      moderate/severe headache to mild/none were similar in groups I and III at 2 h (55
      vs 56%) and 4 h (80 vs 77%). Incidences of headache recurrence (moderate/severe
      any grade of headache) and median times to headache recurrence were also similar:
      22-32% at 16 h in group I and 25-33% at 16.5 h in group II. Sumatriptan was
      superior to placebo in treating headache recurrence: 74 vs 49% (p = 0.017) in
      group I and 70 vs 30% (p = 0.0001) in group II. Thus, one-fourth of patients
      experience headache recurrence at about 16 h after successful treatment of a
      migraine attack with 100 mg oral sumatriptan. A second tablet of sumatriptan at 2
      h does not increase initial efficacy and neither prevents nor delays headache
      recurrence.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7828191
TI  - Migraine, polycythemia and chronic mountain sickness.
AB  - In the epidemiological study among 379 adult men with permanent residence at 4300
      meters (14,200 feet), we found 32.2% with migraine (mostly migraine with aura),
      15.2% with tension-type headache (episodic more than chronic), and 7.2% with
      other headaches. The frequency of migraine increased with age from 30.1% in the
      20-29 year age group to 36.8% in the 50-59 year group. Episodic tension-type
      headaches also showed this trend. We found an age-specific increase in the
      frequency of high hemoglobin (Hb > 213 milligrams), low oxygen saturation (O2
      saturation < 81.5%) and high chronic mountain sickness scores. Male migraineurs
      and those with more than two headaches per month had the highest hemoglobin
      levels and chronic mountain sickness scores when compared with high altitude men
      without headaches.

PMID- 7828192
TI  - White matter MRI hyperintensities in a hundred and twenty-nine consecutive
      migraine patients.
AB  - The most frequently reported abnormal MRI finding in migraine is the presence of
      high signal white matter foci (WMF) on long TR images. Recently, WMF have been
      distinguished in periventricular WMF (PVF), when contiguous to ventricles, and
      deep WMF (DF), when far from these. DF, but not PVF, appear positively correlated
      with cerebrovascular risk factors and are called leukoaraiosis. In this study the
      MRI examination was performed in 129 consecutive migraine patients (83 of them
      had migraine without aura and 46 migraine with aura). In 19.3% of the migraineurs
      studied we observed WMF on T2 weighted images strictly localized in the deep
      white matter (DF). No PVF were observed. These findings were independent of the
      type of migraine and did not correlate with age, sex, disease duration, or
      frequency of attacks. The presence in a subgroup of migraineurs of leukoaraiosis
      (DF), for which a vascular genesis has been hypothesized, suggests that migraine
      could represent, a cerebrovascular risk factor in these patients.

PMID- 7828193
TI  - Bilateral asymmetry of cerebral blood velocity in cluster headache.
AB  - In this study, 69 episodic cluster headache (CH) patients (40 in the active
      phase, 29 in remission period) underwent a complete TCD examination in order to
      verify the relationship between cerebral blood velocities (CBVs) and the clinical
      profile of the disease. Fifteen patients were examined during both phases, while
      7 were monitored during a spontaneous attack. Sixty-three healthy sex and age
      matched controls were also studied. We measured widespread, asymmetric CBV
      activation during the active phase, bilaterally in the anterior circulation and
      also in the posterior circulation. A relative reduction of CBV on the anterior
      cerebral artery pain side, also during remission, suggests a relationship between
      local vasodilation and the autonomic symptoms ipsilateral to pain during CH
      attacks.

PMID- 7828194
TI  - Decreased collagen-induced platelet aggregation and increased platelet arginine
      levels in migraine: a possible link with the NO pathway.
AB  - We studied whole blood platelet aggregation induced by collagen, platelet
      activating factor (PAF) and measured basal platelet L-arginine (L-arg) levels, as
      an indirect index of the nitric oxide (NO) pathway in migraine. Migraine, both
      with and without aura groups, showed a reduced aggregation to collagen, but not
      to PAF, compared with control subjects. Platelet L-arg levels were significantly
      increased in migraine with aura sufferers, whereas the plasma levels were in the
      same range in migraineurs and controls. Platelet hyperesponsiveness to collagen
      stimulation in migraine may be linked to an increased availability of the amino
      acid precursor and an abnormal NO synthesis.

PMID- 7828195
TI  - The insulin tolerance test and ovine corticotrophin-releasing-hormone test in
      episodic cluster headache. II: Comparison with low back pain patients.
AB  - Hypothalamic involvement has been invoked to explain the periodicity of the
      cluster periods and rhythmicity of the pain attacks in cluster headache. To
      explore this hypothesis the ovine corticotrophin-releasing headaches sufferers
      during both cluster period and remission. A group of low back pain patients and
      healthy subjects comprised the control populations. For the o-CRH test, 7 healthy
      subjects, 7 low back pain patients, 6 cluster headache patients in remission, and
      12 in cluster period were studied. Five healthy subjects, 7 low back pain
      patients, 6 cluster headache patients in remission, and 9 cluster period were
      administered the insulin tolerance test. Significantly increased basal cortisol
      levels were found in cluster headache patients in both illness phases (p <
      0.0001), but not in low back pain patients. Significantly reduced cortisol
      response to the o-CRH test was observed in cluster headache patients in both
      phases compared to healthy controls (p < 0.02). A blunted ACTH and cortisol
      response (p < 0.0001 and p < 0.003 respectively) to the insulin tolerance test
      was present in cluster headache patients in both phases of the illness compared
      to healthy subjects and low back pain patients. On the contrary, the ACTH surge
      after insulin induced hypoglycemia was significantly increased in the low back
      pain patient group (p = 0.02). These results suggest that the altered
      hypothalamic-pituitary-adrenal axis responsiveness in cluster headache patients
      is not a consequence of the pain, and point to a central, probably hypothalamic
      derangement in this pathology.

PMID- 7828196
TI  - Immunocyte enumeration in duodenal biopsies of migraine without aura patients
      with or without food-induced migraine.
AB  - The possibility of an IgE-mediated allergic mechanism in food-induced migraine
      remains controversial. Twenty consecutive migraine patients, 11 with food-induced
      migraine, 9 without, were investigated for determination and counting of
      immunocyte populations (IgA, IgM, IgE, IgG containing cells) by biopsies at
      duodenum 2 level. Conventional histology and plasmocyte populations were not
      significantly different between the two groups of migraine patients. This study
      does not support the existence of an IgE-mediated allergic mechanism in food
      induced migraine.

PMID- 7828197
TI  - Personality characteristics before and after treatment of different head pain
      syndromes.
AB  - In order to examine whether, in patients with different types of headache and
      craniofacial pain, MMPI and STAI scores are significantly different before and
      after treatment, 114 patients with tension-type headache (n = 34), atypical
      facial pain (n = 20), temporomandibular joint dysfunction (n = 36), migraine (n =
      16), cluster headache (n = 4), chronic paroxysmal hemicrania (n = 2), trigeminal
      neuralgia (n = 2) were examined. A pain index was calculated (0-10) which
      quantified pattern, duration and frequency of pain. The Italian MMPI (356 item
      abbreviated version) and the STAI tests were administered before and after
      treatment. A paired t-test was used to assess pre- and post-treatment
      differences, and multiple regression analysis was employed to examine whether
      such differences correlated with the improvement in the pain index. In the total
      group after treatment, there was a significant reduction of certain MMPI scores
      (Hs, D, Hy, Pa, Pt, Sc, Si) and of STAI 1 and 2 scores. Separate analysis
      confirmed this among women but not among men. No relation was found between MMPI
      and STAI changes and the degree of improvement as assessed through the pain
      index. Clinical improvement leads to normalization of MMPI profiles and STAI
      scores in women. The psychometric data before treatment were not predictive for
      treatment outcome.

PMID- 7828198
TI  - Ergotamine-induced headache can be sustained by sumatriptan daily intake.
AB  - We describe the case report of a migraine sufferer who developed ergotamine
      induced headache and subsequently replaced ergotamine with daily sumatriptan (100
      mg p.o.). The features of the headache were unchanged except for the presence of
      superimposed migraine-like headaches that occurred every 24 h.

PMID- 7828199
TI  - Intractable headache: aseptic meningitis and sphenoidal sinusitis.
AB  - Sphenoid sinusitis, an uncommon cause of headache, is associated with significant
      morbidity. A 30-year-old man presented with a progressive intractable headache
      and aseptic meningitis. Failure to recognize sphenoid disease on brain CT delayed
      diagnosis; treatment with i.v. antibiotics resolved the disorder.

PMID- 7828200
TI  - Migrainous phenomenon precipitated by lumbar puncture headache.
AB  - This case report describes a patient without personal or family history of
      migraine or other recurrent headaches who developed a typical lumbar puncture
      headache leading to a characteristic migrainous visual field deficit. There was
      no history of analgesic or other medication use or other precipitant, and neither
      symptom recurred in years of follow-up. The sequence of symptoms suggests that
      mechanical distortion or irritation of cranial pain-sensitive structures can
      precede and precipitate the migrainous cortical dysfunction.

PMID- 7828201
TI  - Diagnostic criteria of childhood migraine.

PMID- 7828202
TI  - Outcome measurement for treated and untreated TMD patients using the TMJ scale.
AB  - Changes in symptom profiles of two groups of treated and untreated
      temporomandibular disorders (TMD) patients were measured using the TMJ Scale.
      Forty-nine consecutive TMD patients were included in the study. Of these, 29
      patients were treated using splint therapy, physical therapy, counseling, and non
      steroidal anti-inflammatory (NSAID) medications. Patients completed the TMJ Scale
      questionnaire prior to treatment and at completion of the TMD therapy. Sixty-five
      patients were not treated in any manner, having completed the questionnaire
      during an initial diagnostic study and having declined treatment. They were
      contacted by mail at least four months later and asked to complete the second
      questionnaire if they had not received any treatment. Twenty untreated patients
      returned the completed questionnaire. The initial scale scores for the two groups
      were similar. Comparison of the two tests of both groups revealed the treated
      group improved significantly, while the untreated group remained unchanged,
      except for a statistically non-significant increase of scale scores (increased
      symptom severity) for joint dysfunction and range of motion limitation. Younger
      patients responded more favorably to therapy than older patients. The findings do
      not support the conclusions of the few previous studies that found TMD are often
      self-limiting and rarely progress to chronic intracapsular derangement. The
      findings strongly support the hypothesis that symptom improvement was related to
      treatment and not solely to the passage of time.

PMID- 7828203
TI  - Changes in head and cervical-spine postures and EMG activities of masticatory
      muscles following treatment with complete upper and partial lower denture.
AB  - A clinical stomatognathic, cephalometric and electromyographic (EMG) study was
      performed in relation to 14 subjects (10 women, 4 men), each with an edentulous
      maxilla and residual mandibular dentition before and six months after treatment
      with complete upper and partial lower dentures. The mean age of the subjects was
      54.4 years (range 43-64 years). The mean period of edentulousness and age of
      dentures were 22.5 years (range 15-33 years) and 14.1 (range 1.5-30 years),
      respectively. Natural head position was recorded (using a fluid-level method) and
      measured from cephalograms. EMG activity was measured in relation to masseter and
      temporal muscles. A decrease in clinical dysfunction index was noted in 12 of 14
      subjects (86%). There was no change in cervical inclination, but a slight
      extension of the head was noted after treatment. Rapid recovery of the
      masticatory muscles was reflected in increased EMG activity, especially when
      biting in the maximal intercuspal position. In cases of edentulous maxilla and
      residual mandibular anterior dentition, treatment with a complete upper and lower
      partial denture had a favorable effect on craniomandibular disorders and
      masticatory-muscle function.

PMID- 7828204
TI  - Influence of stabilization occlusal splint on craniocervical relationships. Part
      II: Electromyographic analysis.
AB  - The aim of this study was to determine the effect of stabilization occlusal
      splints on electromyographic (EMG) activity of sternocleidomastoid and trapezius
      muscles in subjects with spasm in the mentioned muscles. A full-arch maxillary
      stabilization occlusal splint was made for each of the 15 subjects. In the
      sternocleidomastoid muscle, tonic and saliva swallowing EMG activity decreased
      significantly with the splint, whereas maximal clenching activity did not change.
      In the trapezius muscle, no significant changes were observed with the occlusal
      splint. The different pattern in both muscles during tonic and swallowing EMG
      activity with the splint is attributed to differences in the synaptic inputs to
      the respective motoneuron pools, suggesting that a differential modulation of the
      motor neuron pools may exist of both muscles, of peripheral and/or central
      origin.

PMID- 7828205
TI  - Temporomandibular disorders and occlusion: an appliance to treat occlusion
      generated symptoms of TMD in patients presenting with deficient anterior
      guidance.
AB  - Temporomandibular disorders (TMD) are of multifactorial origin. If it is
      determined that the patient's occlusal scheme is a contributing factor to their
      TMD symptoms, it is accepted that reversible, noninvasive procedures be
      instituted at the outset of treatment. Splint therapy conforms to this guideline,
      offering temporary, reversible alteration of the occlusal scheme in order to
      provide this relief. In a mutually protected occlusion, the posterior teeth
      accept the occlusal force of closure, while the anterior teeth separate the
      dentition during excursive movements. The purpose of the disclusion splint
      described in this article is to eliminate muscle hypertonicity, along with its
      ensuing problems. This is accomplished by establishing a mutually protected
      occlusion via the guide planes created by the acrylic portions of the splint, but
      not compromising the patient's "freeway" space.

PMID- 7828206
TI  - Diagnostic accuracy of TMJ vibration analysis for internal derangement and/or
      degenerative joint disease.
AB  - Lower joint arthrography and videofluoroscopy were used to diagnose 297 joints
      from temporomandibular disorders (TMD) patients. The surface vibrations of the
      temporomandibular joints (TMJs) were recorded by electrovibratography and a
      parameter set was derived through frequency analysis. Total vibration energies
      were used as the primary separating threshold for abnormal joints. The following
      conditions were statistically discriminated by multi-variate analyses: I)
      meniscal displacement with reduction; II) meniscal displacement with a partial
      disk reduction; III) meniscal displacement without reduction; and IV)
      degenerative joint disease and/or perforation of the disk. Using the total
      vibration energy as a threshold, the diagnostic sensitivity for the abnormal
      joints was 82%, while the diagnostic specificity for the joints with no evidence
      of internal derangement was 75%. Discriminant analysis for the above-mentioned
      four conditions revealed a diagnostic sensitivity of 79.0%, 85.7%, 77.1% and
      76.3% for conditions I, II, III and IV, respectively. The diagnostic specificity
      was 76.2%, 79.9%, 59.0% and 77.9% for conditions I, II, III and IV, respectively.
      It was concluded that vibration analysis of the TMJ could be clinically useful as
      a screening examination for TMD patients.

PMID- 7828207
TI  - Orthopedic jaw movement observations. Part V: Transversal condylar shift in
      protrusive and retrusive movement.
AB  - Unguided protrusive and retrusive mandibular movement was investigated in 76
      asymptomatic volunteers and temporomandibular joint (TMJ) patients using
      computerized axiography. In 38 of these subjects, guided pro-/retrusion was also
      recorded. Measurements were performed in a three-dimensional Cartesian coordinate
      system (x = anteroposterior; y = transversal, toward the hinge axis; z =
      craniocaudal). Transversal shift (y) was measured and evaluated as well as the
      distance "s" and horizontal condylar inclination (HCl) at the point of maximum
      transversal deviation. The patterns of the tracings were analyzed with a view to
      diagnostic improvements. The objective of this study was to evaluate transversal
      shift and to examine the postulate of symmetrical behavior of the TMJs in pro
      /retrusion. The mean mandibular shift was 0.15 mm to the left. This maximum
      deviation was seen in a mean distance "s" of 7.42 mm in relation to the Cartesian
      coordinate system in reference position. These results suggest a functional
      dominance of the right part of the mandible in protrusive and retrusive movement.

PMID- 7828208
TI  - The influence of postoperative treatment on the results of temporomandibular
      joint menisectomy. Part I: Comparison of mandibular opening and closing
      movements.
AB  - In order to evaluate the influence of postoperative treatment on the results of
      temporomandibular joint (TMJ) menisectomy, the maximum voluntary opening and
      closing movements of 67 patients who underwent either total menisectomy or
      partial menisectomy with disk repair were analyzed and compared to those of 10
      normal subjects. The postoperative treatment was classified into three different
      types depending on its strategy. It was observed that postoperative treatment
      which emphasized physical medicine modalities could produce opening and closing
      movements of the mandible closer to the normal range. The effect of the
      postoperative treatment on the results of total menisectomy was more significant
      than that on the results of partial menisectomy with disk repair. Partial
      menisectomy with disk repair resulted in better opening and closing movement than
      total menisectomy.

PMID- 7828209
TI  - Scientific methodology in temporomandibular disorders. Part III: Diagnostic
      reasoning.
AB  - Temporomandibular disorders (TMD), as a cluster of individual diseases and
      disorders, pose new intellectual challenges to the diagnostic skills of dentists.
      New technologies enable dentists to avail themselves of paraclinical data such
      that diagnosis can and should be disease specific or etiology specific. The
      importance of logic in diagnostic reasoning is discussed. Studies of the
      reasoning process of doctors with reputations for having good clinical judgement
      have resulted in protocols of diagnostic reasoning. Three specific strategies are
      presented and discussed-probabilistic, causal and deterministic. The difference
      between intellectual and managerial decisions are explained relative to utility
      of the strategies.

PMID- 7828210
TI  - Characteristics of the light-induced phase response of circadian activity rhythms
      in common marmosets, Callithrix j. jacchus [primates-Cebidae].
AB  - Phase-response experiments using 1-h light pulses (LPs) of 1,100 lux applied
      under constant dim light of 0.3 lux were conducted with common marmosets,
      Callithrix j. jacchus, in order to obtain a complete phase-response curve
      established according to the common experimental procedure in a diurnal primate.
      Maximal phase delays of the free-running circadian activity rhythm (-90 min) were
      induced by LPs delivered at circadian time (CT) 12; e.g., during the beginning of
      the marmosets' rest time, maximal advances (+25 min) were elicited by pulses
      administered during the late subjective night at CT 21. In contrast to rodents,
      neither regular transient cycles nor regular period responses resulted from LP
      applications at different phases. To check whether the underlying period length
      affects the phase response in primates as well, the marmosets' circadian timing
      system was entrained to 25 h by a light:dark (LD) cycle of 12.5:12.5 h. The 1-h
      LPs were delivered during the first circadian cycle produced under constant dim
      light after the entraining LD periods. Here, LPs applied at CT 21 led to phase
      advances exceeding those measured during the steady-state free run. At CT 12,
      minor or no phase delays could be elicited. These findings show that the phase
      shifting effect of LPs on the circadian system of marmosets is similar to that
      observed in other diurnal mammals. Some of the results indicate that in this
      diurnal primate, LP-induced phase shifts may be mediated in part by a light
      induced increase in locomotor activity (arousal).

PMID- 7828211
TI  - Temporal synergism of corticosterone and prolactin in the Syrian hamster,
      Mesocricetus auratus.
AB  - To augment the limited work reported in the literature regarding testing of the
      hormonal temporal synergism hypothesis in Syrian hamsters (Joseph MM, Meier AH.
      Proc Soc Exp Biol Med. 1974;146:1150-5), a large experiment with female hamsters
      was conducted. Forty-eight received corticosterone at 18:00 h on January 21, 23,
      25, 27, and 29 and ovine prolactin at one of six times of day beginning January
      22 for 8 days; 36 received saline (at 18:00) and prolactin at one of the six
      times of day for 8 days; 35 received only prolactin at one of the six times of
      day for 8 days; and 16 received no injections. Twelve hamsters receiving
      corticosterone and prolactin and eight uninjected hamsters were on running
      wheels. The corticosterone and prolactin group not on wheels had a body weight
      gain and no circadian rhythm of weight gain, but did have circadian rhythms of
      response in organ weight, per 100 g of body weight, and in weights of fat pads
      and uteri. The corticosterone and prolactin group with access to running wheels
      gained in body weight and had larger ovaries and smaller fat pads. Hamsters
      receiving saline and prolactin had a body weight gain, but had no circadian
      rhythms of response in organ weights. The hamsters receiving only prolactin
      gained in body weight but had no rhythms of response, except for unexpected
      circadian rhythms in body weight gain and weights of fat pads. The uninjected
      hamsters had a modest weight gain. Most or all hamsters with access to running
      wheels free-ran, and the corticosterone injections did not appear to synchronize
      the locomotor activity rhythms.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7828212
TI  - Response of the sleep-wake rhythm to an 8-hour advance of the light-dark cycle in
      the rat.
AB  - We have studied the effects of an 8-h advance of the environmental light-dark
      (LD) cycle on the sleep-wake rhythm in the rat. Electroencephalograms and
      electromyograms were recorded simultaneously on chart paper through a two-channel
      telemetry system for 3 days before phase shift (baseline) and 8 days during and
      after phase shift. Phase advance of the LD cycle led to an increase in both non
      rapid eye movement (NREM) and REM sleep. The amount of NREM sleep in the light
      period correlated positively with that in the preceding dark period for 4 days
      after phase advance. The duration of REM sleep in the light period correlated
      negatively with that in the preceding dark period. The results suggest that
      homeostatic control of the amount of NREM sleep between the preceding dark period
      and the following light period is disturbed by phase advance of the LD cycle.

PMID- 7828213
TI  - Circadian rhythms of renal hemodynamics in unanesthetized, unrestrained rats.
AB  - Catheters were placed in the jugular vein and femoral artery of male Sprague
      Dawley rats and connected to a specially designed perfusor for continuous
      constant infusion of 0.9% NaCl and a syringe to perform simultaneous and
      intermittent blood collections. This permitted continuous 24-h study of renal
      hemodynamics, estimated by inulin (Cin) and p-amino-hippuric acid (CPAH)
      clearances; Cin represents glomerular filtration rate and CPAH renal plasma flow.
      Animals were individually housed in metabolism cages in a controlled environment
      with light/dark 12:12 h. Urine was collected every 4 h (12:00, 16:00, 20:00,
      24:00, 04:00, and 08:00) and blood sampled at the midpoint of urine collection
      periods. Urine and plasma sodium, potassium, inulin, and PAH were
      spectrophotometrically assessed. During continuous infusion of isotonic saline,
      Cin exhibited circadian changes with large decrease between 12:00 and 20:00 h
      (0.9 +/- 0.2 ml/min) and acrophase at 00:30 h. Rhythmicity in CPAH was similar
      with the minimum between 16:00 and 20:00 h (2.5 +/- 0.3 ml/min) and peak between
      00:00 and 04:00 h (acrophase at 00:25 h). Water and electrolyte excretion were
      also circadian rhythmic with a similar nighttime enhancement and daytime minimum.
      Such circadian changes persisted during continuous 0.9% NaCl infusion for several
      consecutive days. The unanesthetized, unrestrained rat model enables
      investigations in renal chronopharmacology and chronotoxicology.

PMID- 7828214
TI  - Daily variations of functional parameters and density distribution in human blood
      platelets.
AB  - Blood platelets play a critical role in the onset of myocardial infarction, which
      has been shown to have a circadian rhythmicity with a peak incidence in the
      morning. In an attempt to correlate platelet parameters with the outcome of
      cardiovascular diseases, we studied the daily (24-h) variation of the following
      platelet parameters: distribution pattern of functional heterogeneous platelet
      subpopulations; serotonin uptake; ketanserin binding; aggregation upon thrombin,
      serotonin, and ADP stimulation; and platelet count. Furthermore, we analyzed the
      tryptophan and serotonin concentrations in the blood samples. The percentage of
      less dense platelets, which represent the subpopulation with the highest
      preactivation, showed a rhythmicity period of 24 h and an acrophase at 21:18 h.
      The time course of intermediate and high density platelets was inverse to that of
      low density platelets. The serotonin uptake exhibited also a rhythmicity with a
      24-h period. The acrophase was at 13:50 h. The aggregation curves were inverse to
      the ketanserin binding curves. The serotonin concentration exhibited a 12-h
      rhythmicity. The results obtained suggest that (a) changes in platelet activity
      are reflected by several parameters of platelet function that underlie daily
      variations; (b) the aggregation curves show a peak in the morning, with an
      additional peak in the afternoon; and (c) changes in the distribution pattern
      occur independently from variations in platelet functions like aggregation and
      serotonin binding.

PMID- 7828215
TI  - Circadian and ultradian rhythms in heart rate and motor activity of smokers,
      abstinent smokers, and nonsmokers.
AB  - In a field study, heart rate and motor activity were assessed continuously in 12
      male smokers during 2 smoking and 2 abstinence days and in 12 male nonsmokers
      during 4 days. A circadian analysis revealed earlier activity acrophases in
      smokers than nonsmokers and earlier heart rate acrophases in abstinent than
      smoking smokers. Furthermore, heart rate acrophases of smoking smokers
      significantly anticipated activity acrophases, whereas in abstinent smokers and
      nonsmokers the two parameters oscillated in phase. With the use, in smoking
      smokers, of the individual average smoking interval as a hypothetical ultradian
      period length, significant periodicities were found for heart rates in 16 and for
      activity in 15 of 24 observation days. These rhythms were nicotine independent
      and based on heart rate and activity increases prior to lighting up the
      cigarettes. Individual frequency spectra for the 16 h after getting up and the 7
      h after going to bed did not reveal single dominant frequencies but rather
      complex frequency distributions. Power spectra of the daytime data revealed no
      group differences for activity and no heart rate differences between smoking
      smokers and nonsmokers. In abstinent smokers, however, a significant reduction of
      heart rate frequencies slower than 1 cycle/135 min and a significant increase of
      heart rate frequencies faster than 1 cycle/20 min were observed as compared with
      all other groups. This effect persisted over the 2 abstinence days, suggesting an
      activity-independent change in the frequency distribution of heart rates after
      quitting smoking.

PMID- 7828216
TI  - Can insulated skin temperature act as a substitute for rectal temperature when
      studying circadian rhythms?
AB  - We measured rectal, lateral chest wall, and axillary temperature every half hour
      for at least 24 h while subjects were living normal life-styles and keeping a
      sleep/activity diary. We then used a purification method to estimate the decrease
      of temperature due to sleep and the increases due to sitting, standing, walking,
      or exercising, as well as the parameters of the cosine curve that described the
      "purified data." Cosinor analysis of raw and purified data showed that the
      acrophases from both skin sites were much more variable and up to 8 h later than
      were those from the rectum (particularly if exercise had been taken), even though
      the acrophases from the two skin sites were similar to each other. For rectal
      temperature, there was an increase in the size of the masking effect as activity
      progressed through the sequence: sitting, standing or walking, exercising. In
      contrast, for both chest wall and axillary temperatures, although sitting
      produced masking effects similar to those for rectal temperature, masking effects
      due to standing or walking and exercising were much smaller, and sometimes they
      were even less than the masking effects due to sitting. These results indicate
      that our measurements of cutaneous temperature did not act as a substitute for
      rectal temperature, particularly when the subject was physically active rather
      than sedentary.

PMID- 7828217
TI  - Ramadan, health, and chronobiology.

PMID- 7828218
TI  - ESR evidence for the generation of reactive oxygen species from the copper
      mediated oxidation of the benzene metabolite, hydroquinone: role in DNA damage.
AB  - In previous studies, we observed that Cu(II) strongly induces the oxidation of
      hydroquinone (HQ), producing benzoquinone and H2O2 through a Cu(II)/Cu(I) redox
      cycle mechanism. The oxidation of HQ by Cu(II) also results in plasmid DNA
      cleavage. In this study, using ESR spectroscopy we have investigated whether this
      chemical-metal redox system can generate reactive oxygen species which induce DNA
      damage. In order to set the stage for the ESR experiments and the inhibitors to
      be used in these experiments, some preliminary O2 consumption and plasmid DNA
      cleavage experiments were performed. Mixing 100 microM HQ with 10 microM Cu(II)
      in phosphate-buffered saline (PBS) resulted in a marked consumption of O2 and the
      concomitant generation of H2O2, and extensive DNA degradation in chi X-174 RF I
      DNA. The presence of superoxide dismutase (SOD) or mannitol did not affect either
      the O2 consumption, H2O2 generation or DNA damage. In contrast, the Cu(I)
      chelators, bathocuproinedisulfonic acid (BCS) and glutathione (GSH), extensively
      inhibited the HQ/Cu(II)-mediated O2 consumption and DNA damage. The presence of
      catalase also prevented the DNA damage. Although the HQ/Cu(II)-mediated O2
      consumption increased in the presence of azide, azide markedly inhibited the
      HQ/Cu(II)-induced DNA degradation, resulting in primarily open circles. Using ESR
      spectroscopy, it was observed that Cu(II) strongly mediated the formation of
      semiquinone anion radicals from HQ in PBS, which could be blocked by BCS. alpha
      (4-Pyridyl-1-oxide)-N-tert-butylnitrone (4-POBN)-spin trapping experiments showed
      that the interaction of HQ with Cu(II) produced 4-POBN-CH3 and 4-POBN-CH(OH)CH3
      adducts in the presence of dimethyl sulfoxide (DMSO) and ethanol, respectively,
      suggesting that hydroxyl radical or an equivalent reactive intermediate is
      generated from the HQ/Cu(II) system. The presence of catalase, BCS or GSH but not
      SOD completely prevented the formation of 4-POBN-CH3 adduct from the HQ/Cu(II)
      plus 4-POBN/DMSO system. This indicates that both H2O2 and Cu(I) are critical for
      the formation of reactive oxygen from the HQ/Cu(II) system. Anaerobic conditions
      induced an approximately 85% decrease in the formation of 4-POBN-CH3 adduct.
      Reactive oxygen scavenger experiments showed that the formation of the 4-POBN-CH3
      adduct was significantly inhibited by azide but not by mannitol. Overall, the
      above results indicate that through a copper-redox cycling mechanism the copper
      mediated oxidation of HQ generates reactive oxygen species which may participate
      in DNA damage.

PMID- 7828219
TI  - Comparison of expression of aldehyde dehydrogenase 3 and CYP1A1 in dominant and
      recessive aryl hydrocarbon hydroxylase-deficient mutant mouse hepatoma cells.
AB  - The mouse hepatoma cell line Hepa-1 is inducible by 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD) for both CYP1A1 (aryl hydrocarbon hydroxylase, AHH) and class 3
      aldehyde dehydrogenase (ALDH3) enzymes. To test the hypothesis of a common
      regulatory mechanism, several AHH deficient mutants of Hepa-1 were studied for
      their ALDH3 activities and specific mRNA levels before and after TCDD treatment.
      The recessive (with respect to the wild-type Hepa-1) mutants have defects in
      Cypla-1 structural gene (mutant c1) or in the Ah (aryl hydrocarbon) receptor
      (mutants c2 and c6 with decreased levels of Ah receptor; mutant c4 defective in
      the DNA binding of the Ah receptor). The results with these mutants suggested
      that Ah receptor nuclear translocator protein, ARNT, is needed for ALDH3
      expression. Two dominant mutants, one of which is characterized by preventing the
      binding of the Ah receptor complex to DNA, were also studied. Surprisingly, these
      mutants possessed elevated levels of ALDH3 mRNA and enzyme activities which were
      also inducible by TCDD. The binding of Ah receptor-ligand complex to DNA was thus
      not needed for the expression of ALDH3. A dominant repressor for Cypla-1 gene
      transcription did not prevent the derepression or induction of ALDH3. The results
      thus suggest that Aldh-3 gene is regulated by a mechanism independent of the Ah
      receptor.

PMID- 7828220
TI  - Oxidative modification of DNA bases in rat liver and lung during chemical
      carcinogenesis and aging.
AB  - The extent of DNA modification in cancerous rat live and lung tissues was
      investigated and compared to their respective normal tissues. Liver tumors were
      induced by 2-fluorenylacetamide (2-FAA) or N-nitroso-N-2-fluorenylacetamide (N-NO
      2-FAA), and lung tumors were induced by sodium nitrite plus trimethylamine. In
      the DNA samples isolated from these tissues, two pyrimidine-derived and four
      purine-derived modified DNA bases were identified and quantified by gas
      chromatography/mass spectrometry with selected-ion monitoring. These compounds
      were characterized as 5-hydroxyuracil (5-OHUra), thymine glycol (TG), 4,6-diamino
      5-formamidopyrimidine (FapyAde), 2,6-diamino-4-hydroxy-5- formamidopyrimidine
      (FapyGua), 8-hydroxyadenine (8-OHAde), and 8-hydroxyguanine (8-OHGua). Elevated
      amounts of modified DNA bases were found in most cancerous tissues when compared
      to the controls. Chemicals used for tumor induction were responsible for inducing
      DNA lesions that could be promutagenic in vivo and could lead to various types of
      mutations. When endogenous oxidative damage to DNA during aging was examined, a
      roughly 2-fold increase of thymine glycol, 8-OHAde and 8-OHGua was found in aged
      (12 months) rat liver tissues compared to young tissues (1 month). The same
      results were also found in lung tissues, except that the amount of thymine glycol
      exhibited more than a 10-fold increase in aged tissues when compared to young
      tissues. The association of the modified bases with the processes of aging and
      carcinogenesis deserves further investigation.

PMID- 7828221
TI  - Effects of N,N'-bisdimethyl-1,2-ethanediamine dichloride, a double-chain
      surfactant, on membrane-related functions in human erythrocytes.
AB  - The effects of N,N'-bisdimethyl-1,2-ethanediamine dichloride (dioctyldiQAS), a
      double chain surfactant with two positive charges in the polar head, on the
      erythrocyte membrane were studied. At sublytic concentrations dioctyldiQAS
      protected erythrocytes against hypotonic hemolysis, induced the formation of
      sphero-echinocytes, increased passive fluxes of potassium through the membrane,
      decreased the activity of the Na(+)-K(+)-pump and decreased the efflux of
      phosphate. The alterations in membrane-connected functions induced by
      dioctyldiQAS are qualitatively similar to those induced by its single-chain close
      analogue decyltrimethylammonium bromide. DioctyldiQAS, however, exhibited these
      effects at considerably lower concentrations than decyltrimethylammonium bromide.
      This is most likely due to a higher extent of partitioning into the membrane by
      dioctyldiQAS.

PMID- 7828222
TI  - Effects of N-acetylcysteine stereoisomers on oxygen-induced lung injury in rats.
AB  - The effects of the stereoisomers of N-acetylcysteine (L-NAC and D-NAC) on oxygen
      induced lung oedema have been studied in rats. The NAC-isomers were given by an
      osmotic minipump in order to attain continuous administration, either
      intravenously or intragastrically. In some experiments, plasma concentrations of
      NAC, cysteine and glutathione (total concentrations, i.e., concentrations
      obtained after reduction of the samples with dithiothreitol) were recorded.
      Exposure to oxygen induced an almost two-fold increase of the lung wet weight.
      When L-NAC or D-NAC were given intravenously, in dose of 1.1 mmol/day/kg body
      weight, the increase of lung wet weight was prevented by 40-50%. The plasma
      concentrations were approximately 40 microM (L-NAC) and approximately 90 microM
      (D-NAC). Following intragastrical administration of the same doses, plasma
      concentrations of L-NAC and D-NAC reached approximately 3 and approximately 60
      microM, respectively. Using this method of administration, only D-NAC
      significantly diminished the increase of the lung wet weight. The difference in
      plasma concentrations of the NAC isomers, particularly after intragastric
      administration, most likely reflects the fact that L-NAC is effectively
      hydrolysed in most tissues, while D-NAC is resistant to enzymatic hydrolysis,
      thus penetrating largely intact into the systemic circulation. The data presented
      shows that NAC, regardless of stereoconfiguration, will protect the lung against
      oxygen toxicity, provided sufficient systemic levels are obtained. Since D-NAC is
      not a precursor of L-cysteine, formation of glutathione cannot explain the
      protective effects of this isomer. L- and D-NAC may therefore act via direct
      antioxidant/radical scavenging mechanisms and not necessarily as precursors of
      glutathione in this model.

PMID- 7828223
TI  - (Z)-3-(4-bromophenyl)-3-(3-pyridyl)allylamine as substrate for studies of
      myeloperoxidase activity.
AB  - (Z)-3-(4-Bromophenyl)-3-(3-pyridyl)allylamine (CPP 200) is transformed to the
      corresponding chloroimine by hypochlorite ion (ClO-) formed in the presence of
      myeloperoxidase. A scheme for this transformation is given. The influence of
      various compounds on this process has been studied. Cysteamine, cysteine and 6
      chloro-3-hydrazino-pyridazine inhibited the transformation of CPP 200, while some
      p-hydroxyphenyl derivatives increased the rate of transformation of CPP 200. The
      increase seen on addition of the p-hydroxyphenyl derivatives is not a chloride
      dependent reaction. Various mechanisms for the inhibiting effect as well as for
      the activating effect on the transformation of CPP 200 are discussed.

PMID- 7828224
TI  - A special note on Japanese encephalitis vaccine.

PMID- 7828225
TI  - Hippocrates to Penfield: lessons for medical education.

PMID- 7828226
TI  - Epilepsy in the decade of the brain.

PMID- 7828227
TI  - Treating asthmatic children in the UK.

PMID- 7828228
TI  - Immunohistochemical staining for thyroglobulin in poorly differentiated carcinoma
      of the thyroid.
AB  - Paraffin sections of 14 specimens of poorly differentiated tumours of the thyroid
      were stained for thyroglobulin using polyclonal antibodies and a streptavidin
      biotin peroxidase staining system. The better differentiated areas showed
      positive staining, while the poorly differentiated areas gave weakly positive or
      negative staining. Thyroglobulin staining is useful in attributing a thyroid
      epithelial cell origin to a tumour, but negative staining does not exclude this.

PMID- 7828229
TI  - Aspiration cytology of breast lumps.
AB  - The results of 287 aspirations performed on palpable breast lumps over a period
      of 20 months are presented. This is the first documentation of a Sri Lankan
      experience of this technique. The cytological assessment showed 52 malignant, 149
      benign, 8 atypical, 6 suspicious and 72 inadequate aspirates. All lesions with a
      cytological diagnosis of malignancy were confirmed by histological assessment
      (False positives = 0). Histological follow up in 96 of the 149 cytologically
      benign lesions showed that 2 were malignant, giving a false negative rate of
      2.1%. Three atypical lesions (37.5%) and four suspicious (66.2%) and 10
      inadequate aspirates (13.7%) were also malignant.

PMID- 7828230
TI  - Prevalence of retinopathy in a Sri Lankan diabetes clinic.
AB  - OBJECTIVE: To determine the prevalence of diabetic retinopathy among patients
      with non-insulin dependent diabetes (NIDDM) attending a Sri Lankan diabetes
      clinic and assess the skills of non-ophthalmologist in screening for retinal
      disease. RESEARCH DESIGN AND METHOD: One thousand and three consecutive diabetic
      patients were screened for diabetic eye disease using a standardised technique
      based on the WHO Multinational Study. RESULTS: 31.3% (95% confidence intervals
      28.0% to 31.6%) had retinopathy, 23% (95% confidence intervals 21% to 25%) had
      cataract and 20% (95% confidence intervals 17% to 23%) had previously undetected
      refraction errors. 4.1% (95% confidence intervals 2.1% to 6.0%) of patients were
      blind due to advanced retinal disease while 6.2% (95% confidence intervals 5.0%
      to 7.2%) were blind as a result of cataract. General physicians had a 90.6%
      sensitivity and 100% specificity in screening for retinal disease. CONCLUSIONS:
      Retinopathy accounts for significant visual handicap. Untreated cataract is more
      commonly associated with blindness. Undiagnosed errors of refraction account for
      significant visual handicap in Sri Lankan diabetic patients. Physicians trained
      in techniques of retinal screening can correctly assess diabetic retinal changes
      in a high proportion of patients.

PMID- 7828231
TI  - Prevalence of diabetes mellitus and impaired glucose tolerance in a rural Sri
      Lankan community.
AB  - The prevalence of diabetes mellitus and impaired glucose tolerance (IGT) in a
      rural Sri Lankan community adopting the World Health Organization (WHO) criteria
      were 2.5% and 8% respectively. The low socioeconomic status, adequate physical
      exercise and the low prevalence of obesity appear to have not only contributed to
      the low prevalence of diabetes but also has prevented progression from IGT to
      overt diabetes.

PMID- 7828232
TI  - Correlation between Barr bodies and neutrophil drumsticks.
AB  - There is a marked difference between the frequencies of neutrophil nuclear
      drumsticks and mucosal cell Barr bodies in any given woman despite the fact that
      both represent an inactivated X chromosome. We present results of a prospective
      study carried out on 100 normal Saudi females to assess the statistical
      correlation between these two variables. We conclude that each is independent of
      the other. The lack of statistical correlation perhaps relates to maturational
      and nuclear configuration factors.

PMID- 7828233
TI  - Prevalence of Rhesus blood groups in Sri Lanka.
AB  - Rhesus phenotypes were done on random samples of blood of 500 blood donors from
      February 1979 to September 1980. The distribution of Rhesus phenotypes in this
      sample is presented. Although the pattern of distribution of these phenotypes in
      Sri Lankans is similar to that reported in Indians, it differs markedly from that
      reported in Caucasians.

PMID- 7828234
TI  - Schizophrenia in northern Sri Lanka.
AB  - A descriptive study of 148 schizophrenic patients admitted to the University
      Psychiatry Unit in northern Sri Lanka during the first six months of 1986 is
      reported. There were 85 females and 63 males. 65% of the patients belonged to the
      15-34 age group. Nearly half were first admissions. 63% of the patients had a
      positive family history. Firstrank symptoms were elicited in 76% of the patients.
      Paranoid schizophrenia was the commonest subcategory followed by chronic
      schizophrenia. Catatonic schizophrenia was rare. The average period of
      hospitalisation was 21 days, and 81% of the patients had improved on discharge.
      These findings are compared with results from other countries.

PMID- 7828235
TI  - "CHARGE" association.

PMID- 7828236
TI  - Epiglottic cyst aspiration before induction of anaesthesia.
AB  - Vallecular cysts are uncommon and usually do not produce significant symptoms. A
      case history with problems of inducing general anaesthesia for excision of the
      cyst were avoided by aspirating the cyst before induction is discussed.

PMID- 7828237
TI  - Two different presentations of glottic foreign bodies.
AB  - Two cases of laryngeal foreign body (FB) are presented. The incidence of
      laryngeal FBs, variation in the presenting symptoms and the management are
      discussed.

PMID- 7828238
TI  - Patent vitello-intestinal duct: an unusual presentation.
AB  - The case history of a child passing a roundworm through the umbilicus is
      presented. The diagnosis and management of a patent vitello-intestinal duct is
      discussed.

PMID- 7828239
TI  - A child with myocardial infarction--Kawasaki disease.

PMID- 7828240
TI  - Do non-steroidal anti-inflammatory drugs interfere with low dose aspirin therapy?

PMID- 7828241
TI  - Who discovered the AIDS virus?

PMID- 7828242
TI  - Parasitic zoonoses in Sri Lanka (Part 1)

PMID- 7828243
TI  - Anaphylaxis to Depo-Provera?

PMID- 7828244
TI  - Chloramphenicol resistant Salmonella typhi in Trincomalee.

PMID- 7828245
TI  - Cardiac surgical patients must not be denied the benefits of autologous blood
      predonation.

PMID- 7828246
TI  - Monitoring cerebral oxygenation.

PMID- 7828247
TI  - Psychological preparation of children for surgery.

PMID- 7828248
TI  - Autologous blood donation in support of cardiac surgery: a preliminary report on
      a hospital-based autologous donor programme.
AB  - The purpose of this study was to assess the success or otherwise of the
      introduction of an autologous blood programme in support of cardiac surgery in
      reducing patient exposure to allogeneic blood products and to assess the
      guideline of two units as the collection schedule for such patients. Sixty-six
      patients were enrolled in the programme provided they met defined clinical
      conditions and donated one, two or three units of blood at seven-day intervals,
      using isovolaemic conditions. One minor vasovagal adverse reaction was recorded.
      Of the 66 patients, 51 (77%) avoided allogeneic red cells and 42 (64%) received
      no allogeneic product. If each patient deposited two units, 51 (77%) would have
      required no allogeneic red cells; if three units were deposited, 57 (86%)
      patients would have required no allogeneic red cells, but 60 units would be
      surplus to requirements. Comparison of 52 patients for coronary artery bypass
      grafting who were autologous donors, with 130 patients undergoing the procedure
      before the availability of autologous blood, supports the suggestions that there
      is increased readiness to initiate transfusion of autologous blood and that
      exposure to allogeneic red cells is reduced. However, exposure to allogeneic
      products of all kinds is not reduced. It is concluded that the collection of two
      units of autologous blood is appropriate for most eligible patients and that this
      reduces exposure to allogeneic red cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7828249
TI  - The influence of arterial oxygenation on cerebral venous oxygen saturation during
      hyperventilation.
AB  - Cerebral venous oxygen desaturation may occur when hyperventilation is employed
      during neurosurgical procedures. In this study, we examined the effect of
      arterial hyperoxia (PaO2 > 200 mmHg) on jugular bulb venous oxygen tension
      (PjvO2), saturation (SjvO2) and content (CjvO2) in 12 patients undergoing
      anaesthesia for neurosurgical procedures. Under stable anaesthetic conditions,
      the inspired oxygen fraction (FIO2) was varied to give four different levels of
      arterial oxygen tension (PaO2 100-200, 201-300, 301-400, and > 400 mmHg), at two
      levels of controlled hyperventilation (PaCO2(25) and 30 mmHg). In five patients,
      a transcranial Doppler probe was used to insonate the middle cerebral artery
      throughout the study period. Regression lines were constructed for each patient
      for the PjvO2, SjvO2 and the corresponding PaO2 for both levels of PaCO2 (all
      PjvO2-PaO2 and SjvO2-PaO2 regression lines r2 > 0.85, P < 0.0001). From these
      lines we calculated the PjvO2, SjvO2 and CjvO2 at PaO2 of 100, 250 and 400 mmHg,
      at each level of PaCO2 for each patient. At PaCO2 of 25 mmHg, hyperoxaemia
      increased PjvO2 (from 27.6 +/- 1.1 mmHg at PaO2 of 100 mmHg to 30.6 +/- 1.4 and
      33.6 +/- 1.8 mmHg at PaO2 of 250 and 400 mmHg respectively) and SjvO2 (from 54 +/
      3% at PaO2 of 100 mmHg to 60 +/- 3 and 65 +/- 3% at PaO2 of 250 and 400 mmHg
      respectively, P < 0.05). Hyperoxaemia had a similar effect on SjvO2 and PjvO2 at
      a PaCO2 of 30 mmHg.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7828250
TI  - Price stickers do not alter drug usage.
AB  - Anaesthetists choose daily among wide varieties of neuromuscular blocking drugs
      and rapidly acting hypnotic agents. This study sought to determine whether
      definitive, immediate knowledge of drug cost might influence clinician choices,
      ultimately reducing the cost of anaesthesia care. Faculty anaesthetists,
      residents in training, and nurse anaesthetists served as subjects in this
      prospective, sequential, blinded study of prescribing habits. Weekly inventories
      of selected neuromuscular blocking and rapidly acting hypnotic agents were
      performed over 24 wk at a tertiary-care hospital. Supermarket style price
      stickers plainly indicating the hospital cost of each unit of drug appeared
      continually for 13 wk following an initial 11 wk control period. Both actual
      usage data in priced units as well as data normalized by total anaesthesia
      duration underwent comparison between control and priced periods. The usage of
      pancuronium, vecuronium, atracurium, mivacurium, succinylcholine, thiopentone,
      etomidate, and propofol did not differ in the control from the priced periods.
      Pipecuronium decreased after sticker placement (2 vs 1 vials.wk-1 median, P <
      0.05), as did methohexitone (39 +/- 9.0 [SD] vs 29 +/- 11 syringes.wk-1, P <
      0.05). Ketamine usage normalized by total anaesthesia duration increased (P <
      0.05) following sticker placement. The weekly cost of all drugs inventoried
      normalized for caseload did not differ during the measurement periods. Immediate
      cost awareness, implemented simply as price stickers on drug units, had minimal
      impact on clinicians' drug usage in a tertiary care setting.

PMID- 7828251
TI  - Epidural anaesthesia for elective caesarean section does not influence fetal
      umbilical artery blood flow indices.
AB  - This prospective study was completed to determine the influence of epidural
      anaesthesia on the fetoplacental circulation of normal subjects. Thirty-seven
      normal pregnant patients at term, undergoing elective Caesarean section, had
      Doppler measurements of the fetal umbilical artery blood flow velocity before and
      after epidural anaesthesia using lidocaine 2% without epinephrine. There were no
      differences in systolic/diastolic, resistance or pulsality indices following
      epidural anaesthesia. These results suggest that this technique has no adverse
      effect on fetoplacental circulation in normal non-labouring subjects.

PMID- 7828252
TI  - Uterine and umbilical blood flow velocity during epidural anaesthesia for
      caesarean section.
AB  - The purpose of this study was to use colour Doppler to determine the effect of
      epidural anaesthesia on the uterine and umbilical blood flow velocities. After
      determining the precision of the technique, Doppler insonation of the uterine and
      umbilical arteries was performed in consenting non-labouring patients requesting
      epidural anaesthesia for Caesarean section. Patients in Group I were normal and
      those in Group II were at high risk for uteroplacental blood flow abnormalities.
      The pulsatility indexes (PI) of both uterine and umbilical arteries were compared
      at the following times: control, after fluid and after anaesthesia using repeated
      measure analysis of variance. In Group I (n = 30) the PI increased from 0.72 to
      0.82 in the left uterine artery and from 0.71 to 0.85 in the right uterine artery
      (P < 0.05). In Group II (n = 10) the PI increased from 0.67 to 0.85 in the left
      uterine artery (NS) and from 0.98 to 1.38 in the right uterine artery (P < 0.05).
      There was no change in the PI in the umbilical artery. We conclude that the PI of
      the uterine arteries increases after epidural anaesthesia with lidocaine,
      epinephrine and fentanyl but there is no change in the umbilical PI. While these
      changes do not appear to be clinically important in the low-risk population,
      further studies are required to determine the impact on fetuses at high risk for
      in utero hypoxaemia.

PMID- 7828253
TI  - Epidural opioid analgesia after caesarean section: a comparison of patient
      controlled analgesia with meperidine and single bolus injection of morphine.
AB  - The quality of analgesia, patient satisfaction and incidence of side effects
      following a single bolus of epidural morphine were compared with patient
      controlled epidural analgesia (PCEA) with meperidine during the first 24 hr after
      elective Caesarean section. Seventy-five women were randomly assigned to three
      equal groups. Group I received 30 mg epidural meperidine after delivery and PCEA
      with meperidine; Group 2 received 3 mg epidural morphine after delivery and PCEA
      with saline in a double-blind fashion. Group 3 received 3 mg epidural morphine
      after delivery without saline PCEA. Visual analogue pain scores (VAS) were higher
      with PCEA meperidine from 8-16 hr post-operatively (P < 0.05) than in both
      epidural morphine groups. Two patients in Group 1 and one in Group 3 required
      supplemental parental analgesia. The incidence of nausea was 16% in Group 1,
      compared with 52% in Group 2 and 56% in Group 3 (P < 0.01). Pruritus occurred in
      24% of Group 1 patients, 84% of patients in Group 2 and 68% of patients in Group
      3 (P < 0.001). Forty-six percent of patients in Group 1 were very satisfied with
      pain management, compared with 77% in Group 2 and 79% in Group 3. Nurse workload
      was higher in the PCEA study groups than in Group 3 (P < 0.05). A single bolus of
      epidural morphine provides superior analgesia and satisfaction at low cost, but
      with a higher incidence of nausea and pruritus than PCEA with meperidine.

PMID- 7828254
TI  - Comparison of a rigid laryngoscope with the ultrathin fibreoptic laryngoscope for
      tracheal intubation in infants.
AB  - The flexible ultrathin fibreoptic laryngoscope allows placement of endotracheal
      tubes as small as 2.5 mm internal diameter. The purpose of this study was to
      document the safety and efficacy of intubation using an ultrathin fibreoptic
      laryngoscope. Proved safety and efficacy would justify the routine use of
      fibreoptic laryngoscopy in normal infants to maintain skills needed for
      management of the difficult infant airway. In this prospective study, 40 infants
      < 24 mo of age scheduled for elective surgery were randomly divided into two
      equal groups. After inhalation induction of anaesthesia, in 20 infants the
      trachea was intubated using direct rigid laryngoscopy, and in 20 using the
      ultrathin fibreoptic laryngoscope (size 1.8 mm OD) Olympus LFP. Time to
      successful intubation was recorded, as well as blood pressure, heart rate, end
      tidal CO2 and oxygen saturation. Airway trauma in the operating room, the post
      anaesthesia care unit, and on the first postoperative day was recorded. The
      intubation times using rigid laryngoscopy were less than those using fibreoptic
      laryngoscopy (13.6 +/- 0.9 sec (mean +/- SEM) vs 22.8 +/- 1.7 sec; P < 0.01).
      Oxygen saturation and end-tidal CO2 readings were not different between the two
      groups. After intubation, blood pressure and heart rate increased equally in both
      groups, returning to normal within one to two minutes. There was no difference in
      the airway trauma between groups. We conclude that the ultrathin fibreoptic
      laryngoscope is a safe and effective method for tracheal intubation in infants
      and may be used routinely in order to maintain fibreoptic airway skills.

PMID- 7828255
TI  - Reversal of doxacurium and pancuronium neuromuscular blockade with neostigmine in
      children.
AB  - Recovery after doxacurium and pancuronium neuromuscular blockade and their
      acceleration by neostigmine have not been compared in children. Therefore, 60
      paediatric surgical patients aged 2-10 yr (ASA 1-2) were studied. They were
      randomized to receive doxacurium 30 micrograms.kg-1 or pancuronium 70
      micrograms.kg-1 iv during propofol, fentanyl, isoflurane and nitrous oxide
      anaesthesia. Electromyographic (EMG) responses of the adductor pollicis to train
      of-four (TOF) stimulation of the ulnar nerve were recorded every ten seconds
      using a Datex NMT monitor. Six patients in each relaxant group received
      neostigmine (0, 5, 10, 20 or 40 micrograms.kg-1) with atropine by random
      allocation when first twitch height (T1) had recovered to 25% of control.
      Spontaneous recovery after ten minutes was similar following doxacurium (mean +/-
      SEM values of 45.0 +/- 3.9 vs 49.5 +/- 10.0% for T1 and 25.2 +/- 3.8 vs 14.8 +/-
      3.6% for TOF ratios). Dose-responses to neostigmine were calculated from the log
      dose vs logit of T1 or TOF ratio after ten minutes. Neostigmine-assisted recovery
      was not different in the two groups, with ED70 and ED90 doses for T1 of 14.3 +/-
      1.8 and 25.7 +/- 2.7 micrograms.kg-1 for doxacurium and 12.5 +/- 1.7 and 25.3 +/-
      2.3 micrograms.kg-1 for pancuronium. Time to recovery of TOF ratio to 70% after
      neostigmine 40 micrograms.kg-1 was 2.3 +/- 1.0 and 4.2 +/- 1.7 min (P = NS)
      following pancuronium and doxacurium, respectively. Adjusted recovery due to
      neostigmine alone (spontaneous recovery subtracted from the total) required two
      to three times higher doses of neostigmine.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7828256
TI  - Postoperative sore throat in children and the laryngeal mask airway.
AB  - Postoperative sore throat is a minor complaint after general anaesthesia of
      multifactorial aetiology. The purpose of this study was to compare the effect of
      the laryngeal mask airway (LMA) and endotracheal tube (ETT) on postoperative sore
      throat in children. We hypothesized that the incidence of sore throat would be
      less after the use of the LMA. This was a randomized, single-blind study of 112
      patients of age 3 to 12 yr undergoing minor peripheral surgery. The groups were
      similar, except that airway maintenance was either with an LMA or ETT. After
      induction of anaesthesia with O2, N2O and halothane, an LMA or ETT was inserted.
      Anaesthesia was maintained with O2, N2O and halothane. At the end of surgery, the
      ETT was removed in the operating room before airway reflexes had returned. The
      LMA was removed after the patient's airway reflexes had returned in the recovery
      room. On the first postoperative day, the parents were contacted and asked
      whether or not their child had had a sore throat. If a sore throat had been
      present, the parents rated the discomfort as mild, moderate or severe. The groups
      were similar with respect to age, weight, sex and duration of procedure. The
      overall incidence of sore throat was 9%. The difference between the groups (LMA
      13% vs ETT 5%) was not statistically significant. All of the reported sore
      throats were rated as mild. In conclusion, postoperative sore throats after minor
      paediatric surgery is uncommon. If it does occur, it is mild and the incidence is
      unaffected by the choice of an LMA or ETT.

PMID- 7828257
TI  - Sedation with midazolam during regional anaesthesia: is there a role for
      flumazenil?
AB  - The aim of this study was to reassess the efficacy of flumazenil for reversal of
      sedation with midazolam. Twenty-four ASA I or II patients undergoing elective
      surgery under epidural anaesthesia participated. Following epidural block,
      midazolam was administered to keep the patient sleepy but still responsive to
      verbal commands. At the end of surgery the patients were randomly allocated to
      receive, in a double-blind manner, either flumazenil (0.1 mg.ml-1) or placebo.
      The study drug (maximum dose: 10 ml) was titrated until the patient became fully
      awake. Sedation was assessed with the Modified Steward Coma Scale (MSCS), the
      Trieger test (TT) and Critical Flicker Frequency (CFF). The assessments were done
      before anaesthesia (baseline), at the end of surgery immediately before
      administration of study drug, and serially afterwards, at 10, 30, 60, 90, 120,
      150 and 180 min. Analyses of variance for repeated measures and pooled t tests
      were used. The duration of surgery was (mean +/- SD) 0.72 +/- 0.25 hr in the
      flumazenil group and 0.74 +/- 0.28 hr in the placebo group. The total dose of
      midazolam was 7.2 +/- 2.2 mg for the flumazenil group and 8.9 +/- 2.7 mg for the
      placebo group. The volume of study drug administered was 5.5 ml +/- 1.9,
      equivalent to 0.55 mg, for the flumazenil group and 6.7 +/- 2.2 ml for the
      placebo group. Critical Flicker Frequency is the only measure which revealed a
      difference (P < 0.005) between the flumazenil and placebo groups and this
      occurred only at the ten-minute assessment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7828258
TI  - Prophylactic oral ephedrine reduces the incidence of hypotension after
      subarachnoid block.
AB  - The purpose of this study was to demonstrate the efficacy of oral ephedrine in
      preventing hypotension following subarachnoid block. Two hundred women, ASA
      physical status I or II, undergoing lower abdominal surgery were randomly divided
      into two groups (n = 100 each). All patients were given routine oral
      premedication consisting of diazepam 10 mg and ranitidine 150 mg at bed time and
      at 90 min before surgery. In addition, Group I patients received ephedrine 30 mg,
      orally, 30 min before subarachnoid block was administered. Group II received only
      routine premedication. After starting an iv line and preloading with 10 ml.kg-1
      crystalloid, patients were given 0.5% heavy bupivacaine 3.2 to 3.6 ml, depending
      on body weight, intrathecally. Patients with decreases in blood pressure of 20%
      were given ephedrine i.v., in increments, in addition to crystalloids. Despite a
      similar level of block (T3-T4) and i.v. fluids, the total dose of ephedrine
      supplement in Group I was 4.3 +/- 4.8 mg compared with 11.6 +/- 9.4 mg in Group
      II (P < 0.01). Also, 55 patients in Group I required intraoperative inotrope
      supplement compared with 83 in Group II (P < 0.01). We conclude that oral
      ephedrine premedication is a simple and effective way of reducing the incidence
      of hypotension in patients undergoing lower abdominal surgery under subarachnoid
      block.

PMID- 7828259
TI  - Preparing children for the operating room: psychological issues.
AB  - Children respond psychologically to the prospect of surgery in a variable and age
      dependent manner. This review summarizes the psychoanalytic, cognitive,
      behavioural and family system models of child development. It then reviews
      studies of hospitalization and anaesthesia in children. These studies suggest
      that younger children, children previously anaesthetized, and children who
      experience turbulent anaesthetic inductions are at particular risk for
      postoperative behavioural disturbances. Strategies of dealing with children and
      their parents during the perioperative period are discussed. Such strategies
      include: allowing a parent to be present during induction of anaesthesia,
      administering sedative premedication, creating a supportive environment,
      educating children and parents (verbal descriptions, tours, books, videos), and
      establishing rapport with children and their parents. Age-specific techniques of
      establishing rapport with children are discussed. If children are less anxious
      during the perioperative period, not only will they often exhibit less
      behavioural disturbances postoperatively, but they may face subsequent medical
      care more easily.

PMID- 7828260
TI  - Anaesthesia for caesarean section in a patient with Watson's syndrome.
AB  - Watson's syndrome is an uncommon genetic disorder whose features include mental
      retardation and pulmonary valvular stenosis. The purpose of this report is to
      describe one management strategy used successfully to anaesthetize a woman with
      this disorder who presented for Caesarean section. Epidural anaesthesia using
      0.5% bupivacaine without epinephrine in 2-3 ml boluses to a total dose of 15 ml
      was administered over 30 min. Invasive haemodynamic monitoring in the form of
      arterial and central venous catheters were used to guide therapy and help ensure
      maternal and fetal well-being. Intravenous ketamine in doses of 10-20 mg every
      five minutes to a total dose of 245 mg (4.5 mg.kg-1) was used to overcome the
      patient's uncooperative nature and facilitate invasive procedures. Postoperative
      analgesia was provided using 3 mg epidural morphine. The patient was observed in
      the intensive care unit for the first postoperative day and experienced an
      uncomplicated intra- and postoperative course. We conclude that this technique
      represents a safe and effective method for anaesthetizing patients with this
      complicated problem for Caesarean section.

PMID- 7828262
TI  - Canadian Anaesthetists' Society Gold Medal.

PMID- 7828261
TI  - Adjuvant propofol enables better control of nausea and emesis secondary to
      chemotherapy for breast cancer.
AB  - We investigated the prophylactic antiemetic effect of added low-dose infusion of
      propofol in patients exhibiting nausea and vomiting refractory to dexamethasone
      and serotonin antagonist during non-cisplatin chemotherapy for breast cancer. In
      a prospective open longitudinal study, 117 patients who had more than five
      episodes of nausea and vomiting in their first chemotherapy cycle during the
      first 24 hr completed the study. They received in addition to the usual
      prophylactic antiemetic regimen a continuous intravenous infusion of 1 mg.kg-1.hr
      1 propofol started four hours before chemotherapy and continued up to 24 hr for
      the two subsequent cycles. The number of vomiting/nausea episodes, level of
      sedation, patient activity, appetite and preference for future chemotherapy
      cycles were assessed. In the propofol supplemented cycles 90 and 80% of patients,
      during the 1st and 2nd propofol-assisted cycle respectively, were free of nausea
      and vomiting during the first 24 hr after chemotherapy. Patients were more
      frequently active and had more appetite during the propofol-assisted cycles. No
      propofol-associated side effects were observed. We conclude that the addition of
      a subhypnotic infusion of propofol enables better control of nausea and vomiting
      caused by non-cisplatin chemotherapy in the first 24 hr post-treatment.

PMID- 7828263
TI  - Analgesic effects of thoracic epidural bupivacaine and fentanyl.

PMID- 7828264
TI  - Tracheal granulations secondary to wall compression by endotracheal tubes in
      infants.

PMID- 7828265
TI  - Human dura mater permeability.

PMID- 7828266
TI  - Negative arterial to end-tidal CO2 gradients in children.

PMID- 7828267
TI  - Co-axial placement of endobronchial blocker.

PMID- 7828268
TI  - Reversal of multidrug resistance by a novel quinoline derivative, MS-209.
AB  - MS-209, a novel quinoline derivative, was examined for its reversing effect on
      multidrug-resistant tumor cells. MS-209 at 1-10 microM completely reversed
      resistance against vincristine (VCR) in vitro in multidrug-resistant variants of
      mouse leukemia P388 cells (VCR-resistant P388/VCR and Adriamycin (ADM)-resistant
      P388/ADM) and human leukemia K562 cells (VCR-resistant K562/VCR and ADM-resistant
      K562/ADM). MS-209 at 1-10 microM also completely reversed resistance against ADM
      in vitro in P388/VCR cells, K562/VCR cells, and K562/ADM cells. In ADM-resistant
      P388 (P388/ADM) cells, however, ADM resistance was only partially reversed at the
      MS-209 concentrations tested. MS-209 enhanced the chemotherapeutic effect of VCR
      in P388/VCR-bearing mice. When MS-209 was given p.o. at 80 mg/kg twice a day
      (total dose, 160 mg/kg per day) with 100 micrograms/kg VCR, a treated/control
      (T/C) value of 155% was obtained. MS-209 also enhanced the chemotherapeutic
      effect of ADM in P388/ADM-bearing mice. The most prominent effects were obtained
      when MS-209 was given with 2 mg/kg ADM, yielding T/C values of 150%-194% for the
      combined treatment at an MS-209 dose of 200-450 mg/kg. MS-209 inhibited [3H]
      azidopine photolabeling of P-glycoprotein efficiently. Furthermore, the
      accumulation of ADM in K562/ADM cells was increased more efficiently by MS-209
      than by verapamil. These results indicate that MS-209, like verapamil, directly
      interacts with P-glycoprotein and inhibits the active efflux of antitumor agents,
      thus overcoming multidrug resistance in vitro and in vivo.

PMID- 7828269
TI  - Possible cardiac side effects of granisetron, an antiemetic agent, in patients
      with bone and soft-tissue sarcomas receiving cytotoxic chemotherapy.
AB  - The cardiac effect of granisetron, a selective 5-hydroxytryptamine3 receptor
      antagonist, on 12 patients with bone and soft-tissue sarcomas treated by
      cytotoxic chemotherapy consisting of multiple courses was examined. Of the 12
      patients, 4 showed significant electrocardiographical changes, including sinus
      bradycardia, integral change of P-waves, junctional escape beat, and
      atrioventricular (AV) block with Wenckebach phenomenon, indicating stimulatory
      regulation of the vagus nerve. These changes were observed in each patient after
      several courses of chemotherapy but not in the first course. There was no
      correlation between the electrocardiographical changes and the chemotherapeutic
      agents used or the type of tumor present. A patient with osteosarcoma showed
      persistent bradycardia in three courses, all protocols of which contained high
      dose methotrexate. From these findings we conclude that the cardiac responses may
      be due to stimulated activity of the vagal efferent nerve, which is regulated
      reflexly by afferent nerve activity suppressed by granisetron. On the other hand,
      the antiemetic efficacy of granisetron was satisfactory. These results suggest
      that careful observation of the heart is necessary when granisetron is used,
      especially for chemotherapy consisting of repeated multiple courses.

PMID- 7828270
TI  - Intracellular activation and cytotoxic action of RS-1541 against cultured human
      tumor cells.
AB  - RS-1541, an acyl-derivative of rhizoxin (Fig. 1), is a potent antitumor compound.
      This agent showed cytotoxicity in vitro on some cultured human tumor cells,
      although it was less potent than rhizoxin. Rhizoxin exhibited antitumor effects
      by inhibiting the polymerization of tubulin, whereas RS-1541 did not inhibit
      tubulin polymerization in vitro. However, cell cycle analysis in vivo showed that
      the two agents had the same mode of action. The cytotoxicity of RS-1541 was
      enhanced when the initial cell density of the cells was increased. The
      cytotoxicity was also enhanced when the membrane fraction of St-4 cells, which
      were the most sensitive to RS-1541 among the cell lines tested, was added to the
      target cells. When St-4 cells were incubated with [14C]-RS-1541, significant
      amounts of [14C]-rhizoxin were produced within the cells. Further fractionation
      of the crude membrane showed that the activity that enhanced the cytotoxicity of
      RS-1541 (RS-1541-enhancing activity) belonged to the mitochondrial-lysosomal
      fraction, not to the microsomal fraction. Both the enhancing activity and the
      activity that converting [14C]-RS-1541 to [14C]-rhizoxin (RS-1541-converting
      activity) were inhibited by treatment with chloroquine, an inhibitor of lysosomal
      function. Cholesterol esterase derived from Candida cylindracea had RS-1541
      enhancing and -converting activities. These data suggest that RS-1541 exerts its
      cytotoxic action after being converted to rhizoxin within the cells by a
      lysosomal enzyme such as cholesterol esterase.

PMID- 7828271
TI  - A possible mechanism for the cytotoxicity of a polyacetylenic alcohol,
      panaxytriol: inhibition of mitochondrial respiration.
AB  - A polyacetylenic alcohol, panaxytriol, isolated from Panax ginseng C. A. Meyer
      inhibits both tumor cell growth in vitro and the growth of B16 melanoma
      transplanted into mice. Our preliminary studies indicated that panaxytriol
      localizes to the mitochondria in human breast carcinoma cells (Breast M25-SF).
      This study focused on the effects of panaxytriol on mitochondrial structures and
      function in Breast M25-SF. The results indicate that panaxytriol rapidly inhibits
      cellular respiration and disrupts cellular energy balance in Breast M25-SF. At
      concentrations between 11.3 and 180 microM, panaxytriol causes a dose-dependent
      inhibition of the conversion of the tetrazolium (MTT assay) by mitochondrial
      dehydrogenase within 2 h. A 1-h treatment with 180 microM panaxytriol causes a
      significant loss of rhodamine-123 from cells with mitochondria prestained with
      rhodamine-123 (by flow cytometry). Specific toxic changes were observed by
      electron microscopy in the mitochondria of Breast M25-SF within 1 h after
      treatment with more than 180 microM panaxytriol. These data indicate that 180
      microM panxytriol rapidly disrupts cellular energy balance and respiration in
      Breast M25-SF and suggest that panaxytriol may lower cellular ATP concentrations.
      After treatment with 180 microM panaxytriol, cellular ATP levels were 40% of
      those in control cells after 1 h. ATP depletion preceded the loss of cellular
      viability. Neither ATP depletion nor cytolysis was found in human erythrocytes
      that have no mitochondria. Thus, ATP depletion resulting from a direct inhibition
      of mitochondrial respiration is a critical early event in the cytotoxicity of
      panaxytriol.

PMID- 7828272
TI  - Kinetics of mitotic arrest and apoptosis in murine mammary and ovarian tumors
      treated with taxol.
AB  - The kinetics of taxol-induced mitotic arrest and apoptosis in murine mammary
      carcinoma MCA-4 and ovarian carcinoma OCA-I tumors were determined to establish a
      possible causative relationship between mitotic arrest and apoptosis and to see
      whether these cellular effects of taxol would correlate with the extent of its
      antitumor efficacy. Mice bearing 8-mm tumors in a hind leg were given taxol i.v.
      at a dose of 10-80 mg/kg. Both tumors responded to taxol by significant growth
      delay or transient regression; in general, the response was greater as the dose
      of taxol was increased. For kinetics studies the mice were treated with 60 mg/kg
      taxol given once when tumors were 8 mm in size or twice, with the second dose
      being given 3 days after the first. At various times ranging from 1 to 96 h after
      treatment with taxol, tumors were histologically analyzed to quantify mitotic and
      apoptotic activity. After a single dose of taxol, mitotic arrest was visible at 1
      h, and the mitotic index increased with time to reach peak values of 36% in MCA-4
      tumors and 22% in OCA-I tumors at 9 h. The index then declined to a baseline of
      1%-3% at 3 days for MCA-4 tumors and 1 day for OCA-I tumors. Apoptosis followed
      mitotic arrest, beginning at the time of peak mitotic arrest, increasing to the
      highest level of about 20% at 18-24 h after treatment and gradually declining to
      the normal level of 3%-6% after 3-4 days. Nuclear material progressively
      condensed in mitotically arrested cells, culminating in the frank appearance of
      multiple apoptotic bodies. The change in cell morphology plus the dynamics of
      apoptosis development imply that a large percentage of tumor cells arrested in
      mitosis by taxol die by apoptosis. Kinetic analysis undertaken after the second
      dose of taxol showed a considerably lower percentage of cells arrested in mitosis
      as compared with that seen after a single dose, and the induction of apoptosis by
      the second dose was minimal. However, the antitumor efficacy of the second dose
      of taxol was similar to or better than that of the first dose, implying that in
      addition to mitotic arrest and apoptosis, there exist other mechanisms by which
      taxol exerts its antitumor action.

PMID- 7828273
TI  - Biological disposition of intravenously administered 131I-labeled anti-EGF
      receptor antibody (RG 83852) in the rat.
AB  - RG 83852 is a murine monoclonal antibody that preferentially inhibits the high
      affinity binding of epidermal growth factor (EGF) to its receptor. Since
      overexpression of EGF receptor has been implicated in some human malignancies,
      the antibody is under investigation as a potential anticancer agent. The present
      work characterized the tissue distribution and elimination of 131I-labeled
      antibody in rats following i.v. administration. 131I-RG 83852 was given in a 2.22
      mg/kg dose to rats, and 4, 24, 48, and 72 h afterwards 131I activity excreted in
      the urine and feces and that present in various tissues was determined. The
      plasma contained the highest concentration of radioactivity at all times. At 4 h
      the plasma contained about 12% of the injected dose (ID)/ml, and radioactivity in
      this compartment accounted for almost 70% ID. The plasma elimination of 131I
      derived activity occurred linearily at a rate of about 0.48% ID/h. Except in the
      thyroid, the concentration of 131I activity in all tissues was much lower than in
      the plasma (tissue-to-plasma ratio < or = 0.1). In the thyroid, accumulation of
      radioactivity (4% ID at 24 h) was presumably due to trapping of 131I released
      from the antibody as a result of biodegradation. The urinary excretion occurred
      at a rate of about 0.5% ID/h; the fecal excretion was minimal. The
      biodistribution results are consistent with the protein structure of the
      antibody. Based on the available disposition data, it is proposed that
      elimination of the antibody involves degradation, a process that follows zero
      order kinetics, followed by excretion of the labeled product(s) in the urine.

PMID- 7828274
TI  - Conversion of mitomycin C to 2,7-diaminomitosene and 10-decarbamoyl 2,7
      diaminomitosene in tumour tissue in vivo.
AB  - The progress of mitomycin C (MMC) bioreduction was studied in vivo in the rat Sp
      107 mammary carcinoma after intra-tumoural injection of either 100 micrograms or
      1 mg. 2,7-Diaminomitosene (2,7-DM) was utilised as a primary bioreductive
      metabolite and 10-decarbamoyl 2,7-diaminomitosene (DC 2,7-DM) served as a
      secondary bioreductive metabolite, both of which were measured by high
      performance liquid chromatography. 2,7-DM and DC 2,7-DM were produced rapidly,
      achieving close to their maximal concentrations at the earliest time point
      studied [5 min]. 2,7-DM was cleared rapidly from the tumour with apparent half
      lives of 5 and 35 min after the low and high drug doses, respectively. DC 2,7-DM
      had a longer apparent half-life of 130 min at the higher dose but, as compared
      with 2,7-DM, was only a minor metabolite [the area under the curve (AUC) of 2,7
      DM was 5.6-fold that of DC 2,7-DM]. At the lower drug dose, DC 2,7-DM was not
      detectable. Rapid formation and disappearance of bioreductive metabolites of MMC
      may account for the failure of previous studies to detect these products in vivo.

PMID- 7828275
TI  - Persistence of cisplatin-induced DNA interstrand crosslinking in peripheral blood
      mononuclear cells from elderly and young individuals.
AB  - DNA interstrand crosslinks (ISCL) produced by the incubation of human peripheral
      blood mononuclear cells (PBMs) with cisplatin (CDDP) were measured in two
      populations of volunteers, one aged less than 25 years and the other, greater
      than 72 years. The technique of fluorometric alkaline elution was used to measure
      DNA interstrand crosslinking with time after a 1-h exposure to drug. The samples
      from the young group showed a more consistent pattern of crosslink formation and
      removal, with extensive, or in some cases complete, repair at 48 h. Those from
      the elderly group showed considerable inter-individual variation and
      significantly higher mean levels of crosslinking at 24 and 48 h. No samples
      showed complete repair at 48 h in this population. These results indicate an
      impaired DNA repair capacity in the cells from the elderly group. This may be a
      factor in the poor tolerance of chemotherapy in the ageing population.

PMID- 7828276
TI  - Modulation of resistance to cisplatin by amphotericin B and aphidicolin in human
      larynx carcinoma cells.
AB  - The aim of this study was to examine whether resistance to cisplatin [cis
      diamminedichloroplatinum (II)] (CDDP) could be overcome by amphotericin B,
      cyclosporin A and aphidicolin in two sublines of human larynx carcinoma HEp2
      cells. The sensitivity of parental and cisplatin-resistant CA3 and CK2 cells to
      amphotericin B, cyclosporin A and aphidicolin, and also the effects of these
      drugs (given in maximal nontoxic concentrations) on cisplatin sensitivity were
      determined by clonogenic survival assay. CA3 and CK2 cells were sensitive to
      amphotericin B, and resistant to cyclosporin A and aphidicolin, compared with
      their parental cells. Amphotericin B increased cisplatin toxicity 2-fold in CA3
      cells and 2.7-fold in CK2 cells, while it had no effect in parental HEp2 cells.
      Cyclosporin A did not influence the sensitivity of examined cells to cisplatin.
      The sensitizing effect of aphidicolin was more obvious in cisplatin-resistant
      cells. Cisplatin toxicity was increased by aphidicolin: 1.5-fold in HEp2 cells, 2
      fold in CA3 cells, and 1.9-fold in CK2 cells. Therefore, the resistance to
      cisplatin in human larynx carcinoma CA3 and CK2 cells can be partially reversed
      by amphotericin B and aphidicolin.

PMID- 7828277
TI  - No synergistic activity of epirubicin and interferon-alpha 2b in the treatment of
      hepatocellular carcinoma.
AB  - Single-agent activity for anthracyclines reflected by response rates of 10%-30%
      has been reported in patients with advanced hepatocellular carcinoma (HCC).
      Preclinical data indicate that alpha-interferon could enhance the cytotoxic
      activity of the anthracycline Adriamycin or its analog epirubicin. In a phase
      I/II study, 31 patients with biopsy-proven inoperable HCC were treated with
      interferon-alpha 2b given s.c. at a dose of 3 x 10(6) units/m2 per day for 5 days
      per week plus weekly epirubicin given at 25 mg/m2 as an i.v. bolus. The protocol
      called for 4 consecutive weeks of treatment followed by 1 week off treatment. In
      all, 15 patients had been previously treated; 6 patients had failed hormonal
      therapy (tamoxifen), 5 patients had failed prior anthracycline treatment, and 4
      patients had received chemoembolization of the tumor and had subsequently
      progressed. A total of 30 patients were evaluable for response. In all, 1 patient
      (3%) achieved a partial response for 8+ months and 11 patients (35%) achieved
      stabilization of disease. Six patients had a fall in alphafetoprotein (AFP)
      values of > 50% during therapy. The median survival for all patients was 9.5
      months (range, 3-34+ months). The main side effects were hematological toxicity
      and fever, both of which were considered tolerable. As an indicator of the
      immunostimulatory effects of interferon, an elevation in serum markers of
      inflammation [C-reactive protein (CRP), beta 2-microglobulin] was found in 15%
      20% of patients. All patients had measurable Mx protein production during
      therapy, but these effects were not correlated to the clinical response. The
      clinical response rate achieved in this trial indicates that the combination of
      interferon and epirubicin, at least when used on the schedule reported herein, is
      not superior to treatment with either agent alone for patients with advanced HCC.
      However, single patients achieved a prolonged progression-free interval (8-10+
      months) on this therapy, and it may therefore be an option for patients who have
      failed prior hormonal or single-agent anthracycline therapy.

PMID- 7828278
TI  - 5-Fluorouracil plus 5-methyltetrahydrofolate in advanced pancreatic cancer. GLISP
      (Gruppo Ligure Studio Pancreas).
AB  - A total of 20 patients with advanced pancreatic adenocarcinoma were enrolled in a
      phase II trial testing the activity of 5-fluorouracil given at 370 mg/m2 as a
      rapid i.v. bolus for 5 consecutive days, preceded by a rapid i.v. bolus of 200
      mg/m2 5-methyltetrahydrofolic acid. The treatment was repeated every 4 weeks. The
      median age of the patients was 68 years and their median Eastern Cooperative
      Oncology Group (ECOG) performance status was 1. There were 7 patients with
      locally advanced disease and 13 with distant metastases (median, 2 sites). A
      median of 3 monthly cycles of treatment (range, 1-7) were given, with a
      corresponding dose intensity of 396 mg/m2 per week (86% of that planned). No
      complete response, 1 partial response, and 8 cases of disease stabilization were
      obtained. In general the regimen was well tolerated, with only 2 patients
      suffering from grade 3 stomatitis or diarrhea; the most common toxicity was
      nausea, which was experienced by almost 50% of the patients. The combination of 5
      methyltetrahydrofolate plus 5-fluorouracil appears as little effective in this
      disease as 5-fluorouracil plus 5-formyltetrahydrofolate (leucovorin). It is
      suggested that bolus 5-fluorouracil is so inactive as an "effector agent" against
      pancreatic cancer that its biochemical modulation with exogenous high-dose
      reduced folates cannot improve the therapeutic outcome produced by the
      fluoropyrimidine in these patients.

PMID- 7828279
TI  - Vincristine and oral etoposide in refractory multiple myeloma.
AB  - A total of 15 patients with refractory multiple myeloma (MM; 4 primary
      unresponsive and 11 relapsed and resistant to re-induction/salvage therapy)
      received i.v. vincristine on day 1 and oral etoposide daily for 4 days, the
      treatment being repeated at 3-weekly intervals. The patients were re-assessed
      after three cycles of chemotherapy, and non-responders received no further
      therapy. There was no complete or partial response. A minimal response was seen
      in two patients, and two others showed stable disease. None of the responses was
      sustained, and all patients eventually had progressive disease. It is concluded
      that combination chemotherapy with vincristine and oral etoposide given by this
      schedule is unlikely to be of any value in refractory myeloma.

PMID- 7828280
TI  - The role of methoxymorpholino anthracycline and cyanomorpholino anthracycline in
      a sensitive small-cell lung-cancer cell line and its multidrug-resistant but P
      glycoprotein-negative and cisplatin-resistant counterparts.
AB  - The cytotoxic action of two morpholino anthracyclines, methoxymorpholino
      anthracycline (MRA-MT, FCE 23,762) and cyanomorpholino anthracycline (MRA-CN),
      was compared with the cytotoxicity of doxorubicin (DOX), the topoisomerase II
      inhibitor etoposide (VP-16), the topoisomerase I inhibitor camptothecin,
      methotrexate, and cisplatin in GLC4, a human small-cell lung-cancer cell line, in
      GLC4-Adr, its P-glycoprotein (Pgp)-negative, multidrug-resistant (MDR; 100-fold
      DOX-resistant) subline with overexpression of the MDR-associated protein (MRP)
      and a lowered topoisomerase II activity, and in GLC4-CDDP, its cisplatin
      resistant subline. GLC4-Adr was about 2-fold cross-resistant for the morpholino
      anthracyclines and GLC4-CDDP was, relative to GLC4, more resistant for the
      morpholino anthracyclines than for DOX. Overall, MRA-CN was about 2.5-fold more
      cytotoxic than MRA-MT. The cytotoxicity profile of the morpholino anthracyclines
      in these cell lines mimicked that of camptothecin.

PMID- 7828281
TI  - Hypersensitivity and cross-reactivity to cisplatin and analogues.
AB  - We report on a 49-year-old woman with relapsing ovarian cancer who developed a
      hypersensitivity reaction (HSR) to carboplatin and, subsequently, to cisplatin.
      This patient was known to be allergic to Co-Amoxiclav and talc, both giving rise
      to a transient macular skin rash, but had no other history of atopy. Similar
      cases, including some of life-threatening severity, have been reported in the
      literature. These severe reactions may prevent a small population of young
      patients from receiving effective therapy with cisplatin or its analogues,
      treatment known to be associated with a significant improvement in survival in
      germ-cell tumours, ovarian cancer and osteogenic sarcoma.

PMID- 7828282
TI  - Cerebrospinal fluid concentrations of carboplatin in a patient without blood
      brain barrier disruption.

PMID- 7828283
TI  - NHLBI clinical guidelines. Another look.

PMID- 7828284
TI  - Differential expression of tissue factor protein in directional atherectomy
      specimens from patients with stable and unstable coronary syndromes.
AB  - BACKGROUND: Tissue factor (TF) is a cell membrane-associated protein that
      catalyzes the rate-limiting step of the extrinsic coagulation pathway, which is
      the major source of thrombin production in vivo. To explore the potential role
      that TF may play in ischemic coronary syndromes, directional coronary atherectomy
      specimens were tested for the presence of TF protein using immunohistochemical
      techniques. METHODS AND RESULTS: Frozen sections from atherectomy specimens in 61
      patients were examined for TF expression using an IgG murine monoclonal antibody
      against human TF. Patients were classified according to their admission diagnosis
      as having either an unstable or a stable coronary syndrome. An unstable coronary
      syndrome was defined as either angina pectoris occurring at rest or post
      myocardial infarction (< 1 week) angina. Stable coronary syndromes included
      patients with stable, progressive, and new-onset (< 6 weeks) angina without rest
      pain. TF was detected in 15 (43%) of 35 patients with unstable coronary syndromes
      versus only 3 (12%) of 26 patients with stable coronary syndromes (odds ratio,
      5.7; 95% confidence interval, 1.3 to 24.3; P = .018). Within the subgroup of
      patients with unstable coronary syndromes, TF was detected in 14 (60%) of 25
      patients with de novo lesions versus only 1 (10%) of 10 patients with a
      restenosis lesion (P < .02). An additional 8 patients with stable coronary
      syndromes due to a restenosis lesion were also negative for TF. Therefore, the
      overall incidence of TF expression was only 6% (1 of 18) in restenosis lesions
      compared with 33% (14 of 43) in de novo lesions (P < .03). CONCLUSIONS: This
      study provides the first description of TF protein expression in human coronary
      artery lesions in vivo. Tissue factor was readily detected in de novo lesions in
      patients with unstable coronary syndromes, suggesting a role for TF in the
      pathogenesis of this disease process. Conversely, TF was rarely detected in
      patients with restenosis lesions even if the resulting clinical presentation was
      an unstable coronary syndrome. These results may have implications for the
      management of patients with unstable angina from de novo lesions and patients
      with ischemic symptoms from a restenosis lesion.

PMID- 7828285
TI  - The safety of intracoronary ultrasound. A multicenter survey of 2207
      examinations.
AB  - BACKGROUND: Intracoronary ultrasound (ICUS) is increasingly used in clinical
      practice to study the natural history of coronary artery disease and to assess
      the effects of intracoronary, catheter-based interventions. However, the risk
      associated with the procedure is not well documented. METHODS AND RESULTS: ICUS
      studies performed in 28 centers were retrospectively included; these centers
      agreed to contribute to the study among a total of 60 centers initially invited.
      Among the 2207 ICUS studies, 505 (23%) were performed in heart transplant
      recipients and 1702 (77%) in nontransplant patients. Indication for ICUS was
      diagnostic imaging in 915 (41%), drug testing in 244 (11%), and guidance for
      intracoronary interventions in 1048 patients (47%). There were no complications
      in 2034 patients (92.2%). In 87 patients (3.9%), complications occurred but were
      judged to be "not related" to ICUS by the operator. In 63 patients (2.9%), spasm
      occurred during ICUS imaging. In 9 patients (0.4%), complications other than
      spasm were judged to have a "certain relation" to ICUS, including acute
      procedural events in 6 (3 acute occlusion, 1 embolism, 1 dissection, and 1
      thrombus) and major events in 3 patients (2 occlusion and 1 dissection; all
      resulting in myocardial infarction). In 14 patients (0.6%), complications with
      "uncertain relation" to ICUS were recorded, including acute procedural events in
      9 (5 acute occlusion, 3 dissection, and 1 arrhythmia) and major events in 5
      patients (2 myocardial infarction and 3 emergency coronary artery bypass
      surgery). The incidence of acute procedural or major complications judged to be
      associated with ICUS (uncertain relation or certain relation to ICUS) was
      compared in different patient groups. The complication rate was higher in
      patients with unstable angina or acute myocardial infarction (2.1% events) as
      compared with patients with stable angina pectoris and asymptomatic patients
      (0.8% and 0.4%, respectively; chi 2 = 10.9, P < .01). These complications were
      also more frequent in patients undergoing interventions (1.9%) as compared with
      transplant and nontransplant patients undergoing diagnostic ICUS imaging (0% and
      0.6%, respectively; chi 2 = 13.5, P < .001). Adverse events were few, and no
      association was detected between these events and the size or type of ICUS
      catheter used. CONCLUSIONS: ICUS is associated with (but not necessarily the
      direct cause of) a minor acute clinical risk. Vessel spasm is the most frequent
      event occurring during ICUS. Other complications predominantly occur in patients
      with acute coronary syndromes and during guidance for intervention.

PMID- 7828286
TI  - Soluble interleukin-2 receptor levels in patients with dilated cardiomyopathy.
      Correlation with disease severity and cardiac autoantibodies.
AB  - BACKGROUND: There is evidence that autoimmunity plays an important role in the
      initiation and progression of myocardial injury in dilated cardiomyopathy.
      Abnormalities of both cellular and humoral immunity have been described in this
      disease. Soluble interleukin-2 receptor (sIL-2R) levels in the serum reflect
      activation of T lymphocytes in the periphery or in tissues. The present study
      explored the possibility that activation of cellular immunity is frequent in
      patients with idiopathic dilated cardiomyopathy and may have functional
      consequences. METHODS AND RESULTS: Serum sIL-2R levels were determined with an
      enzyme-linked immunosorbent assay in 50 dilated cardiomyopathy patients, 30
      patients with ischemic heart disease, and 22 normal control subjects. In
      addition, the presence of anti-beta-receptor and antimyosin antibodies was sought
      in the serum of cardiomyopathy patients. High sIL-2R levels (> 1400 pg/mL) were
      found in 38% of the dilated cardiomyopathy patients but only 6% of the ischemic
      heart disease patients. The group of sIL-2R-positive patients was characterized
      by higher average age, a higher percentage of women, and more severe disease
      (lower ejection fraction, higher left ventricular filling pressures, and lower
      cardiac output). Although the prevalence of cardiac autoantibodies did not
      correlate with the presence of high sIL-2R levels, higher titers of
      autoantibodies were found predominantly in the sIL-2R-positive group.
      CONCLUSIONS: T-lymphocyte activation, as reflected in elevated sIL-2R levels, is
      frequent in patients with dilated cardiomyopathy and is associated with more
      severe disease. Cellular and humoral immune activation may correlate with
      progression of the disease process.

PMID- 7828287
TI  - Maximal coronary flow reserve and metabolic coronary vasodilation in patients
      with diabetes mellitus.
AB  - BACKGROUND: Structural and functional abnormalities of the coronary
      microcirculation have been reported in experimental diabetes mellitus. The
      purpose of this study was to evaluate coronary microvascular function in human
      diabetes. METHODS AND RESULTS: Twenty-four diabetic and 31 nondiabetic patients
      were studied during cardiac catheterization. A Doppler catheter or guidewire was
      used to measure changes in coronary blood flow velocity in a nonstenotic artery.
      Maximal coronary blood flow reserve was determined by using intracoronary
      adenosine or papaverine. Coronary dilation in response to an increase in
      myocardial metabolic demand was assessed by using rapid atrial pacing. Maximal
      vasodilator responses to papaverine and adenosine were compared in 12 diabetic
      patients. Maximal pharmacologic coronary flow reserve was depressed in diabetic
      (2.8 +/- 0.2, n = 19) compared with nondiabetic (3.7 +/- 0.2, n = 21, P < .001)
      patients. During atrial pacing, the decrease in coronary vascular resistance was
      attenuated in the diabetic (-14 +/- 3%) compared with the nondiabetic (-24 +/-
      2%, P < .05) patients. Differences in coronary microvascular function between
      diabetic and nondiabetic patients were not attributable to differences in drug
      therapy, resting hemodynamics, or incidence of hypertension. In 12 diabetic
      patients the maximal coronary vasodilator responses to papaverine and adenosine
      were similar. CONCLUSIONS: This study demonstrates both reduced maximal coronary
      vasodilation and impairment in the regulation of coronary flow in response to
      submaximal increases in myocardial demand in patients with diabetes mellitus.
      These microvascular abnormalities may lead to myocardial ischemia in the absence
      of epicardial coronary atherosclerosis in some circumstances, and thus contribute
      to adverse cardiovascular events in diabetic patients.

PMID- 7828288
TI  - PQ segment depression in acute Q wave inferior wall myocardial infarction.
AB  - BACKGROUND: PQ segment deviation is almost as characteristic as the classic ST
      segment deviation and is detected in most patients with pericarditis. However, as
      infarction-associated pericarditis remains over the infarct zone, PQ segment
      depression is observed much less often in patients with acute myocardial
      infarction. METHODS AND RESULTS: We designed this study to examine the clinical
      significance of PQ segment depression in acute Q wave inferior myocardial
      infarction. We examined 171 consecutive patients with acute Q wave inferior
      myocardial infarction by means of auscultation, ECG, and two-dimensional
      echocardiography. The diagnosis of pericarditis was made on the basis of
      pericardial rub detected by more than two observers during the first 3 days after
      admission. At least 0.5 mm of PQ segment depression from the TP segment lasting
      more than 24 hours in both limb and precordial leads was considered diagnostic of
      PQ segment depression. CONCLUSIONS: PQ segment depression was present in 14
      patients and absent in 157 patients. Eleven patients with and 55 patients without
      PQ segment depression had advanced asynergy (akinesis or dyskinesis) in the
      posterior segments, whereas 9 patients with and 20 patients without PQ segment
      depression had pericardial rub. When multivariate analysis was performed to
      determine the important variables related to the occurrence of PQ segment
      depression, pericardial rub was selected with advanced asynergy of the posterior
      segment as significant factors related to PQ segment depression. Major
      complications (ventricular fibrillation, sustained ventricular tachycardia,
      cardiogenic shock, need for pacing) were present in 63 patients; 9 with (64%) and
      54 without (34%) PQ segment depression. PQ segment depression was one of the
      clinical signs of more extensive damage extending to the posterior segments and
      increased incidence of major complications.

PMID- 7828289
TI  - Intake of mercury from fish, lipid peroxidation, and the risk of myocardial
      infarction and coronary, cardiovascular, and any death in eastern Finnish men.
AB  - BACKGROUND: Even though previous studies have suggested an association between
      high fish intake and reduced coronary heart disease (CHD) mortality, men in
      Eastern Finland, who have a high fish intake, have an exceptionally high CHD
      mortality. We hypothesized that this paradox could be in part explained by high
      mercury content in fish. METHODS AND RESULTS: We studied the relation of the
      dietary intake of fish and mercury, as well as hair content and urinary excretion
      of mercury, to the risk of acute myocardial infarction (AMI) and death from CHD,
      cardiovascular disease (CVD), and any cause in 1833 men aged 42 to 60 years who
      were free of clinical CHD, stroke, claudication, and cancer. Of these, 73
      experienced an AMI in 2 to 7 years. Of the 78 decreased men, 18 died of CHD and
      24 died of CVD. Men who had consumed local nonfatty fish species had elevated
      hair mercury contents. In Cox models with the major cardiovascular risk factors
      as covariates, dietary intakes of fish and mercury were associated with
      significantly increased risk of AMI and death from CHD, CVD, and any death. Men
      in the highest tertile (> or = 2.0 micrograms/g) of hair mercury content had a
      2.0-fold (95% confidence interval, 1.2 to 3.1; P = .005) age- and CHD-adjusted
      risk of AMI and a 2.9-fold (95% CI, 1.2 to 6.6; P = .014) adjusted risk of
      cardiovascular death compared with those with a lower hair mercury content. In a
      nested case-control subsample, the 24-hour urinary mercury excretion had a
      significant (P = .042) independent association with the risk of AMI. Both the
      hair and urinary mercury associated significantly with titers of immune complexes
      containing oxidized LDL. CONCLUSIONS: These data suggest that a high intake of
      mercury from nonfatty freshwater fish and the consequent accumulation of mercury
      in the body are associated with an excess risk of AMI as well as death from CHD,
      CVD, and any cause in Eastern Finnish men and this increased risk may be due to
      the promotion of lipid peroxidation by mercury.

PMID- 7828290
TI  - Temporal changes in myocardial perfusion patterns in patients with reperfused
      anterior wall myocardial infarction. Their relation to myocardial viability.
AB  - BACKGROUND: Several studies demonstrated ischemic microvascular damage in
      patients with acute myocardial infarction (AMI). In this study, myocardial
      contrast echocardiography (MCE) was used to assess the temporal changes in
      myocardial perfusion after reflow and to investigate the relation between MCE
      findings and myocardial viability. METHODS AND RESULTS: MCE was performed with
      the intracoronary injection of sonicated microbubbles before and shortly after
      coronary reflow and 1 month later in 45 patients with anterior wall AMI. MCE
      before reflow was analyzed to determine the risk area as an area of contrast
      defect in the apical long-axis view. MCE images after reperfusion were analyzed
      to determine peak contrast intensity, which should be in proportion to the
      concentration of microbubbles within the microvasculature and in the infarcted
      and normal myocardium, and the ratio of these (PI ratio) was used to assess
      microvascular integrity. Areas of residual contrast defect were expressed as a
      ratio to those of left ventricular myocardial (RCD ratio) to assess the spatial
      extent of the MCE "no reflow." Regional wall motion (RWM, SD per chord) in the
      territory of the left anterior descending coronary artery was determined by the
      centerline method in both the acute and late stages. Although the PI ratio was
      extremely low shortly after coronary reflow, it increased in the late stage of
      AMI with the improvement in regional contractile function (RWM, -3.2 +/- 0.5
      versus -2.6 +/- 1.0, P < .01; PI ratio, 0.44 +/- 0.25 versus 0.60 +/- 0.29, P <
      .01). Reduction in the RCD ratio was observed even in 15 patients with MCE no
      reflow in the acute stage (0.33 +/- 0.09 versus 0.16 +/- 0.11, P < .01). Then we
      investigated the relation between residual contractile function and microvascular
      integrity in the late stage. A significant correlation was found between the PI
      ratio and RWM (r = .73, P < .001) in the late stage of the AMI. CONCLUSIONS: (1)
      Recovery from ischemic microvascular damage is generally observed in the late
      stage of AMI in association with improvement in myocardial contractile function.
      The degree of improvement in contractile function and microvascular integrity,
      however, varies among patients. (2) Contrast peak intensity in the late stage of
      infarction may provide a useful estimate of myocardial viability.

PMID- 7828291
TI  - Dobutamine echocardiography in myocardial hibernation. Optimal dose and accuracy
      in predicting recovery of ventricular function after coronary angioplasty.
AB  - BACKGROUND: Myocardial hibernation is a condition of chronic left ventricular
      dysfunction associated with severe coronary artery disease whereby significant
      recovery of function occurs after revascularization. Identification of
      hibernating myocardium has important prognostic and therapeutic implications. The
      presence of contractile reserve as assessed by dobutamine echocardiography may be
      promising in the detection of hibernation. We designed a prospective study to
      evaluate the accuracy and optimal dose of dobutamine echocardiography for
      predicting recovery of ventricular function after angioplasty in patients with
      stable coronary artery disease and ventricular dysfunction. METHODS AND RESULTS:
      Twenty patients with stable coronary artery disease and segmental ventricular
      dysfunction scheduled for coronary angioplasty underwent dobutamine
      echocardiography before revascularization using incremental doses of 2.5, 5, 7.5,
      10, 20, 30, and 40 micrograms/kg per minute every 3 minutes. Digital images of
      all eight stages were displayed simultaneously (two quad screens side by side)
      and interpreted using a 16-segment ventricular model and a 6-grade scoring
      system. Serial resting echocardiograms before, early (< 1 week), and late (> or =
      6 weeks) after angioplasty were digitized and randomized in a quad-screen format
      for the assessment of recovery of function. Wall motion score index in the
      revascularized regions decreased from 2.86 +/- 0.76 before angioplasty to 2.12 +/
      1.03 late after angioplasty (P < .05). Of 320 ventricular segments, 148 had
      abnormal wall motion at baseline and 114 were revascularized. Recovery of
      function (> or = 2 grades) occurred in 25% of revascularized segments early and
      in 33% late after angioplasty. Of the 34 abnormal segments not revascularized,
      recovery of function occurred in only 1. During dobutamine echocardiography,
      abnormal segments exhibited one of four responses: biphasic (improvement at low
      dose and worsening at high dose) in 28% of segments, sustained improvement
      (persistent improvement till peak dose) in 18%, worsening in 15%, and no change
      in 39%. A biphasic response had the highest predictive value (72%) for recovery
      of function followed by worsening only (35%), while the lowest was seen with a
      "no-change" or sustained improvement response (13% and 15%). Combining biphasic
      and worsening responses resulted in a sensitivity of 74% and specificity of 73%
      for assessment of recovery of individual segments and 90% and 60%, respectively,
      for functional recovery of individual patients (n = 10). In segments with a
      biphasic response, the low dose at which improvement in wall motion was most
      prevalent (84%) was 7.5 micrograms/kg per minute and increased to 94% when the 5
      and 7.5 micrograms/kg per minute doses were displayed. The reworsening phase of
      the biphasic response was usually seen with doses > or = 20 micrograms/kg per
      minute but was also observed as early as the 7.5 micrograms/kg per minute dose.
      CONCLUSIONS: The wall motion response during dobutamine echocardiography is
      useful in the prediction of recovery of ventricular function after
      revascularization in patients with stable coronary artery disease and ventricular
      dysfunction. The administration of low as well as high doses of dobutamine is
      needed for optimal evaluation.

PMID- 7828292
TI  - Clinical follow-up of patients undergoing percutaneous mitral balloon valvotomy.
AB  - BACKGROUND: This study is the clinical follow-up (20 +/- 12 months; range, 6 to
      49 months) of 327 patients who had percutaneous mitral balloon valvotomy (PMV) at
      the Massachusetts General Hospital. METHODS AND RESULTS: There were seven in
      hospital deaths. Patients were divided into two groups according to their
      echocardiographic score; 211 patients had echocardiographic scores < or = 8 and
      116, echocardiographic scores > 8. Patients with echocardiographic scores > 8
      were older (64 +/- 11 versus 48 +/- 14 years, P < .01), and more had atrial
      fibrillation (65% versus 40%, P < .01), calcium under fluoroscopy (81% versus
      29%, P < .01), and previous surgical commissurotomy (30% versus 16%, P < .01)
      than patients with echocardiographic scores < or = 8. With PMV, mitral valve area
      increased from 1.0 +/- 0.3 to 2.2 +/- 0.8 cm2 in patients with echocardiographic
      scores < or = 8 and from 0.8 +/- 1 to 1.7 +/- 0.7 cm2 in those with
      echocardiographic scores > 8. Rates of survival (98 +/- 2% versus 72 +/- 11%),
      survival with freedom from mitral valve replacement (91 +/- 4% versus 55 +/-
      13%), and survival with freedom from combined events (79 +/- 10% versus 39 +/-
      18%) at follow-up were greater in patients with echocardiographic scores < or = 8
      (P < .00005). Cox regression analysis identified the echocardiographic score as
      the most important unfavorable intermediate long-term follow-up prediction factor
      after PMV. CONCLUSIONS: The excellent intermediate long-term clinical follow-up
      of patients with echocardiographic score < or = 8 and no calcified mitral valves
      suggests that PMV may be the treatment of choice in this group of patients.

PMID- 7828293
TI  - Multicenter validation of a risk index for mortality, intensive care unit stay,
      and overall hospital length of stay after cardiac surgery. Steering Committee of
      the Provincial Adult Cardiac Care Network of Ontario.
AB  - BACKGROUND: A multicenter population-based study was conducted to develop and
      validate a risk index for mortality, intensive care unit (ICU) length of stay,
      and postoperative length of stay after cardiac surgery. METHODS AND RESULTS: Data
      were collected from 13,098 patients undergoing cardiac surgery between April 1,
      1991, and March 31, 1993, at all nine adult cardiac surgery institutions in
      Ontario, Canada. A six-variable risk index (age, sex, left ventricular function,
      type of surgery, urgency of surgery, and repeat operation) was developed using
      logistic regression analysis to predict in-hospital mortality, ICU stay in days,
      and postoperative stay in days after cardiac surgery in a derivation set of 6213
      patients who had cardiac surgery during fiscal year 1991 (April 1, 1991, to March
      31, 1992). The index predicted mortality, prolonged ICU stay (> or = 6 days), and
      prolonged postoperative length of stay (> or = 17 days) after cardiac surgery
      with areas under the receiver-operating characteristic (ROC) curve of 0.75, 0.66,
      and 0.69, respectively, in an independent validation set of 6885 patients who had
      cardiac surgery during fiscal year 1992 (April 1, 1992, to March 31, 1993).
      Increasing risk scores were associated with greater mortality rates and longer
      ICU and postoperative stays at all nine institutions. CONCLUSIONS: Mortality, ICU
      length of stay, and postoperative length of stay after cardiac surgery can be
      predicted using a simple six-variable risk index. The index has potential
      application as a risk stratification tool for comparing patient outcomes and
      resource use among different hospitals and surgeons.

PMID- 7828294
TI  - Role of cardiac beta 2-receptors in cardiac responses to exercise in cardiac
      transplant patients.
AB  - BACKGROUND: In healthy human hearts, beta 2-receptor-mediated chronotropic and
      inotropic responses contribute to the cardiac responses to beta-agonists. A
      (patho)physiological relevance for beta 2-receptor-mediated responses has so far
      not been demonstrated, in part because beta 1-receptor-mediated responses to
      cardiac neuronally released norepinephrine can mask beta 2-receptor-mediated
      responses. METHODS AND RESULTS: In the present study, we evaluated the blood
      pressure and heart rate responses to bicycle exercise in cardiac transplant
      patients (n = 7) compared with patients with essential hypertension (n = 8) on
      placebo and two doses of the beta 1-selective beta-blocker atenolol (25 and 50
      mg/d) and the nonselective beta-blocker nadolol (20 and 40 mg/d), each dose for 1
      week using a double-blind, randomized, crossover design. Exercise was performed 3
      hours after dosing, using a stepwise increase in load until exhaustion. Exercise
      performance was less in the transplant patients and significantly further (25%)
      decreased by nadolol. Exercise caused equivalent increases in plasma
      norepinephrine in the two groups, but more marked increases in plasma epinephrine
      in the transplant patients despite less exercise. In the essential hypertension
      patients, systolic blood pressure increased by 80 mm Hg on placebo and 60 mm Hg
      on either blocker. The increase in heart rate (by about 75 beats per minute) was
      inhibited by 10% and 20% by the lower and higher doses, respectively, similar for
      the two blockers. In contrast, in the transplant patients, systolic blood
      pressure increased by 60 mm Hg on placebo, but this increase was totally blocked
      by either blocker. The heart rate increase (by 50 beats per minute on placebo)
      was blunted (dose related) by either blocker but 50% more by nadolol versus
      atenolol. CONCLUSIONS: The present study shows that cardiac beta 2-receptors
      contribute to a clear extent to the heart rate responses to endogenous
      circulating catecholamines in the absence of cardiac neuronally released
      norepinephrine. Nonselective beta-blockade probably is less well tolerated in
      cardiac transplant patients compared with beta 1-selective blockade.

PMID- 7828295
TI  - Losartan in heart failure. Hemodynamic effects and tolerability. Losartan
      Hemodynamic Study Group.
AB  - BACKGROUND: The aim of the present study was to assess the short- and long-term
      effects of multiple doses of the angiotensin II receptor antagonist losartan in
      heart failure. METHODS AND RESULTS: A multicenter, placebo-controlled, oral,
      multidose (2.5, 10, 25, and 50 mg losartan once daily) double-blind comparison in
      patients with symptomatic heart failure and impaired left ventricular function
      (ejection fraction < 40%). Invasive 24-hour hemodynamic assessment was performed
      after the first dose and after 12 weeks of treatment. Clinical status and
      tolerability of treatment with losartan over the 12-week period were also
      evaluated. One hundred fifty-four patients were enrolled, of which 134 met the
      protocol criterion of baseline pulmonary capillary wedge pressure > or = 13 mm
      Hg. During short-term administration, systemic vascular resistance (SVR) (largest
      reduction against placebo of 197 dyne.s-1.cm-5 at 4 hours) and blood pressure
      fell significantly with 50 mg, lesser decreases were seen with 25 mg, and no
      discernible effects were seen with 2.5 and 10 mg. After 12 weeks of treatment,
      similar effects were seen on SVR and blood pressure (maximal fall in SVR against
      placebo, 318 dyne.s-1.cm-5 at 5 hours with 50 mg). In addition, pulmonary
      capillary wedge pressure fell with 2.5, 25, and 50 mg (largest reduction against
      placebo of 6.3 mm Hg at 6 hours with 50 mg), cardiac index rose with 25 and 50
      mg, and heart rate was lower with all active treatment groups. Active treatment
      was well tolerated, and excess cough was not reported. CONCLUSIONS: This study
      showed that oral losartan administered to patients with symptomatic heart failure
      resulted in beneficial hemodynamic effects with short-term administration, with
      additional beneficial hemodynamic effects seen after 12 weeks of therapy. Clear
      effects were seen with both 25 and 50 mg, with the greatest effect seen with 50
      mg.

PMID- 7828296
TI  - Comparison of five antihypertensive monotherapies and placebo for change in left
      ventricular mass in patients receiving nutritional-hygienic therapy in the
      Treatment of Mild Hypertension Study (TOMHS).
AB  - BACKGROUND: Increased left ventricular mass (LVM) by echocardiography is
      associated with increased risk of cardiovascular disease. Thus, it is of interest
      to compare the effects of both pharmacological and nonpharmacological approaches
      to the treatment of hypertension on reduction of LVM. METHODS AND RESULTS:
      Changes in LV structure were assessed by M-mode echocardiograms in a double
      blind, placebo-controlled clinical trial of 844 mild hypertensive participants
      randomized to nutritional-hygienic (NH) intervention plus placebo or NH plus one
      of five classes of antihypertensive agents: (1) diuretic (chlorthalidone), (2)
      beta-blocker (acebutolol), (3) alpha-antagonist (doxazosin mesylate), (4) calcium
      antagonist (amlodipine maleate), or (5) angiotensin-converting enzyme inhibitor
      (enalapril maleate). Echocardiograms were performed at baseline, at 3 months, and
      annually for 4 years. Changes in blood pressure averaged 16/12 mm Hg in the
      active treatment groups and 9/9 mm Hg in the NH only group. All groups showed
      significant decreases (10% to 15%) in LVM from baseline that appeared at 3 months
      and continued for 48 months. The chlorthalidone group experienced the greatest
      decrease at each follow-up visit (average decrease, 34 g), although the
      differences from other groups were modest (average decrease among 5 other groups,
      24 to 27 g). Participants randomized to NH intervention only had mean changes in
      LVM similar to those in the participants randomized to NH intervention plus
      pharmacological treatment. The greatest difference between groups was seen at 12
      months, with mean decreases ranging from 35 g (chlorthalidone group) to 17 g
      (acebutolol group) (P = .001 comparing all groups). Within-group analysis showed
      that changes in weight, urinary sodium excretion, and systolic BP were moderately
      correlated with changes in LVM, being statistically significant in most analyses.
      CONCLUSIONS: NH intervention with emphasis on weight loss and reduction of
      dietary sodium is as effective as NH intervention plus pharmacological treatment
      in reducing echocardiographically determined LVM, despite a smaller decrease in
      blood pressure in the NH intervention only group. A possible exception is that
      the addition of diuretic (chlorthalidone) may have a modest additional effect on
      reducing LVM.

PMID- 7828297
TI  - Radiofrequency ablation of intra-atrial reentrant tachycardia after surgical
      palliation of congenital heart disease.
AB  - BACKGROUND: Intra-atrial reentrant tachycardia (IART), also called atrial
      flutter, is a common and potentially lethal complication of surgical correction
      of congenital heart disease. Medical management of IART is often problematic,
      which prompts an investigation of the utility of radiofrequency (RF) ablation for
      management of these arrhythmias. METHODS AND RESULTS: Ten consecutive patients
      referred for treatment of recurrent IART after surgery for congenital heart
      disease were studied. Median age was 18.4 years, and median duration of
      arrhythmia was 6.4 years; a median of three antiarrhythmic drugs had been tried.
      Surgical procedures used were Fontan (6), Mustard/Senning (2), and biventricular
      repair (2). Intracardiac electrophysiological study demonstrated 30 distinct IART
      circuits, defined by activation sequence and cycle length. Mean IART cycle length
      was 323 +/- 114 ms. Cycle length was significantly longer in IART circuits that
      were successfully ablated compared with those that were not (381 versus 248 ms, P
      < .001). RF ablation was attempted in 22 of these circuits. Ablation sites were
      targeted to presumed exit points from zones of slow conduction by
      electrophysiological criteria. Sites chosen in this manner clustered in four
      distinct areas of the right atrium. Of 22 IART circuit ablations attempted, 17
      (77%) resulted in acute termination of the tachycardia. In 8 of 10 patients in
      whom at least one IART circuit was successfully ablated, 4 are free of clinical
      tachycardia and 3 are improved over short-term follow-up. No complications were
      encountered. CONCLUSIONS: Multiple IART circuits may be present in patients after
      surgery for congenital heart defects. Activation sequences observed were diverse
      and different from those observed in atrial flutter in patients with normal
      anatomy. Interruption of IART circuits by RF ablation is feasible using mapping
      techniques aimed at identifying an exit point from a zone of slow conduction.
      Short-term follow-up suggests that RF ablation may be a useful adjunct in
      management of IART in these difficult patients.

PMID- 7828298
TI  - Time- and frequency-domain analyses of the signal-averaged ECG in patients with
      arrhythmogenic right ventricular dysplasia.
AB  - BACKGROUND: Arrhythmogenic right ventricular dysplasia (ARVD) is characterized by
      recurrent ventricular tachycardia of right ventricular origin and a
      cardiomyopathy with hypokinetic areas involving the free wall of the right
      ventricle. Subjects have a risk of sudden cardiac death, particularly during
      sports and strenuous exercise. Routine clinical examinations may be normal, but
      fragmented or delayed electrograms are usually recorded in the right ventricle of
      these patients. However, the frequency with which late potentials are detected by
      conventional time-domain analysis of the signal-averaged ECG (SAECG) is not high.
      This study evaluated the usefulness of the frequency-domain analysis of the SAECG
      in addition to the conventional time-domain analysis for a screening test to
      detect patients with ARVD. METHODS AND RESULTS: SAECG was recorded by using a
      bipolar X, Y, and Z lead system in 28 patients with ARVD (mean age, 38 +/- 13
      years) and 35 age-matched normal subjects (mean age, 35 +/- 11 years). The
      conventional time-domain analysis of the SAECG was performed at two different
      high-pass filter settings, 25 and 40 Hz, and the low-pass cutoff frequency was
      fixed at 250 Hz. The fast-Fourier transform analysis of SAECG was performed using
      a Blackman-Harris window. Area ratio 1 (area of 20 to 50 Hz)/(area of 0 to 20 Hz)
      and area ratio 2 (area of 40 to 100 Hz)/(area of 0 to 40 Hz) were calculated. In
      the conventional time-domain analysis, 20 (71%) and 18 (64%) patients had
      positive criteria at filter settings of 25 and 40 Hz, respectively. In the
      frequency-domain analysis, 18 (64%) and 20 (71%) patients had abnormal values in
      area ratios 1 and 2, respectively. Combining the time- and frequency-domain
      analyses, all patients were judged positive, with a sensitivity of 100% and a
      specificity of 94%. CONCLUSIONS: Each result of the time- and frequency-domain
      analyses revealed that both methods had equivalent value. Combining the two
      domain analyses improved the sensitivity without reducing the specificity. These
      findings suggest that combining the time- and frequency-domain analyses of the
      SAECG may be useful as a screening test to detect patients with ARVD.

PMID- 7828299
TI  - Fractal clustering of ventricular ectopy correlates with sympathetic tone
      preceding ectopic beats.
AB  - BACKGROUND: Fractal geometric analysis of ventricular ectopy yields a fractal
      dimension, which can range from zero to one and is inversely related to
      clustering of ventricular premature contractions (VPCs). Low values of this
      fractal dimension, which reflect significantly nonuniform distributions of
      ventricular ectopy, are found in patients with life-threatening ventricular
      arrhythmias and predict adverse outcomes in selected patients with congestive
      heart failure and with mitral regurgitation. However, the physiological mechanism
      and correlates of the fractal dimension are unknown. METHODS AND RESULTS: To
      explore the physiological correlates of clustered ventricular ectopy, we studied
      30 patients with a history of sustained ventricular tachycardia or ventricular
      fibrillation who had inducible sustained monomorphic ventricular tachycardia
      during electrophysiological study and also underwent drug-free 24-hour ambulatory
      ECG. In addition to fractal dimension (determined by use of our previously
      described algorithm), we measured the mean RR interval (+/- SD) for all sinus
      beats preceding a sinus beat and for all sinus beats preceding a single VPC and
      the mean root-mean-square difference (RMSSD) of all windows of 15 successive RR
      intervals (excluding ectopic beats) preceding a sinus beat and preceding a single
      VPC. Based on the directional changes of mean RR (a measure of both sympathetic
      and parasympathetic tone) and of RMSSD (a measure of parasympathetic tone), each
      patient's inferred relative sympathetic tone preceding ventricular ectopy was
      classified as increased, unchanged, or decreased. If these values changed
      concordantly, relative sympathetic tone was indeterminate. Fractal dimension did
      not correlate with the mean RR interval, SD of the RR interval, or RMSSD
      preceding sinus beats or preceding VPCs (all P > .10). In 20 patients, fractal
      dimension was significantly lower among those with increased relative sympathetic
      tone (n = 14) than those with unchanged or decreased sympathetic tone (n = 6, P =
      .008). Ten patients had indeterminate relative sympathetic tone. CONCLUSIONS:
      Clustering of ventricular ectopy, as measured by the fractal dimension, is
      observed in patients at increased risk of sudden cardiac death. A low fractal
      dimension (clustered ventricular ectopy) is related to changes in heart rate and
      heart rate variability that are consistent with transient increases in cardiac
      sympathetic tone.

PMID- 7828300
TI  - Marfan syndrome. Long-term survival and complications after aortic aneurysm
      repair.
AB  - BACKGROUND: Development of surgical therapy for aortic aneurysms and dissections
      has led to treatment of the life-threatening cardiovascular complications
      associated with Marfan syndrome. The present study determines the effect of
      surgical therapy on the life expectancy of patients with Marfan syndrome and the
      clinical course of these patients after aortic aneurysm repair. METHODS AND
      RESULTS: Medical records were reviewed on 192 patients with Marfan syndrome who
      underwent aortic aneurysm repair during the past 26 years; 103 patients were
      interviewed, and complete preoperative and postoperative medical information was
      obtained. Survival curves were generated, and data were analyzed. The median
      cumulative probability of survival was 61 years, significantly increased compared
      with the median survival of 47 years for patients with Marfan syndrome determined
      30 years ago (P < .0006). The majority of patients (53%) had second surgeries to
      repair subsequent aneurysms or dissections at other sites, the vast majority of
      which involved the aorta. The most common pattern of aneurysm repair was proximal
      ascending aortic aneurysm repair, followed by descending thoracic aneurysm
      surgery. The following variables predicted patients requiring second vascular
      surgeries: presence of acute or chronic dissection at the time of the first
      surgery, hypertension after the first surgery, and a history of smoking.
      CONCLUSIONS: The life expectancy of patients with Marfan syndrome undergoing
      surgical repair of aortic aneurysms has improved and is consistent with increased
      survival. After initial repair of an ascending aortic aneurysm, a significant
      number of patients have subsequent surgeries at other sites throughout the aorta,
      indicating Marfan syndrome is a disease involving the entire aorta. Patients who
      had a dissection at the time of the first aortic surgery were more likely to
      require subsequent aortic surgery than were patients who underwent prophylactic
      composite graft repair of an aortic aneurysm.

PMID- 7828301
TI  - Determinants of echocardiographic aortic root size. The Framingham Heart Study.
AB  - BACKGROUND: Previous studies that evaluated the determinants of aortic root size
      have not yielded uniform results. We examined the relations of age, height,
      weight, body surface area, sex, and blood pressure to echocardiographically
      determined aortic root size in a population-based cohort. METHODS AND RESULTS:
      The study sample consisted of 1849 men and 2152 women in the Framingham Heart
      Study and Framingham Offspring Study who were free of clinically apparent cardiac
      disease when echocardiography was performed. Aortic root measurements were made
      by M-mode echocardiography using a leading-edge-to-leading-edge technique. The
      relations of age, height, weight, body surface area, and blood pressure variables
      (contemporary and those obtained 8 years before) to aortic root dimension were
      examined by use of sex-specific correlations and linear regression analyses. Age,
      height, weight, and sex emerged as the principal determinants of aortic root
      dimensions in adults (cumulative R2 = .2085 in men and .2327 in women). The
      additional effect of contemporary or previous blood pressure measures was small
      and revealed direct associations of aortic root dimension with mean arterial and
      diastolic blood pressures and inverse associations with pulse and systolic blood
      pressures. Previous blood pressure measurements did not contribute significantly
      to prediction of aortic root size once contemporary blood pressure variable
      entered the models. Results of regression analyses using a sex-pooled data set
      showed that on average, the aortic root measurement in women was 2.4 mm smaller
      than that of men of comparable age, height, and weight. Logistic regression was
      used to assess the likelihood of aortic root enlargement according to blood
      pressure levels. After adjustment for age, height, and weight, the odds ratio of
      aortic dilation for a 1-SD increment in systolic pressure was 0.70 (95% CI, 0.52
      to 0.95) in men and 0.79 (95% CI, 0.60 to 1.04) in women; the odds ratio for a 1
      SD increment in diastolic pressure was 1.22 (95% CI, 0.91 to 1.63) in men and
      1.33 (95% CI, 1.01 to 1.73) in women. CONCLUSIONS: Age, height, weight, and sex
      emerged as the principal determinants of aortic root dimensions. The additional
      influences of blood pressure measurements were small; direct associations of
      aortic root dimensions with mean arterial and diastolic blood pressures and
      inverse associations with pulse and systolic blood pressures were observed.
      Additional prospective studies are needed to confirm these observations and to
      assess the impact of aortic root dimensions on the incidence of hypertension.

PMID- 7828302
TI  - Do patients with primary pulmonary hypertension develop extensive central
      thrombi?
AB  - BACKGROUND: Distinguishing chronic major vessel thromboembolic pulmonary
      hypertension from primary pulmonary hypertension is critical because the
      treatment options differ markedly. Surgical thromboendarterectomy is potentially
      curative in the former condition, whereas oxygen, vasodilators, perhaps
      anticoagulation, and lung transplantation are the options for the latter. The
      development of large thrombi in the main, right, or left pulmonary arteries has
      not been previously described in patients with primary pulmonary hypertension.
      METHODS AND RESULTS: Three pulmonary hypertensive patients with massive thrombi
      in the central pulmonary arteries are described. The data indicate that the large
      central thrombi in these three patients were not hemodynamically significant. In
      none did perfusion lung scans demonstrate segmental or larger defects.
      CONCLUSIONS: Large central thrombi can develop in patients with primary pulmonary
      hypertension. Perfusion lung scans that do not demonstrate segmental or larger
      defects should alert physicians to this possibility. Chest computed tomography
      and other studies identifying such thrombi are not adequate in distinguishing
      such a development from operable chronic major vessel thromboembolic
      hypertension. Careful review of lobar and segmental artery findings and the
      pulmonary angiogram, angioscopy, and cardiac catheterization data demonstrating
      the hemodynamic significance (or lack thereof) of these thrombi are essential in
      making this important distinction. Furthermore, these observations may constitute
      an additional indication for anticoagulant therapy in primary pulmonary
      hypertension.

PMID- 7828303
TI  - Proximal jet size by Doppler color flow mapping predicts severity of mitral
      regurgitation. Clinical studies.
AB  - BACKGROUND: Recent studies have shown that many instrument and physiological
      factors limit the ability of color Doppler total jet area within the receiving
      chamber to predict the severity of valvular regurgitation. In contrast, the
      proximal or initial dimensions of the jet as it emerges from the orifice have
      been shown to increase directly with orifice size and to correlate well with the
      severity of aortic insufficiency. Only limited data, however, are available
      regarding the value of proximal jet size in mitral regurgitation, and it has not
      been examined in short-axis or transthoracic views. The purpose of the present
      study, therefore, was to evaluate the relation between proximal jet size and
      other measures of the severity of mitral regurgitation. METHODS AND RESULTS: In
      49 patients, the anteroposterior height of the proximal jet as it emerges from
      the mitral valve was measured in the parasternal long-axis view; proximal jet
      width and area were measured in the short-axis view at the same level. Results
      were compared with regurgitant volume and fraction by pulsed Doppler subtraction
      of aortic and mitral flows in 47 patients without more than trace aortic
      insufficiency; with angiographic grade determined within 24 hours in 33
      catheterized patients; and with angiographic regurgitant fraction in 13 patients
      who were in normal sinus rhythm and had no significant aortic and tricuspid
      insufficiency. Proximal jet height, width, and area correlated well with Doppler
      regurgitant volume and fraction (r = .86 to .95; SEE = 7.7 to 9.0 mL; 5.9% to
      7.3%). Proximal jet size could also be used to distinguish angiographic grades of
      mitral regurgitation with minimal overlap (P < .0001) and correlated well with
      angiographic regurgitant fraction (r = .85 to .91; SEE = 4.1% to 5.1%).
      CONCLUSIONS: Proximal jet size correlates well with established measures of the
      severity of mitral regurgitation. It is conveniently available with transthoracic
      clinical scanning and should be useful in the routine evaluation of patients with
      mitral regurgitation.

PMID- 7828304
TI  - Induction of plasminogen activator inhibitor type-1 (PAI-1) by proinsulin and
      insulin in vivo.
AB  - BACKGROUND: Fasting hyperinsulinemia (reflected by elevations in immunoreactive
      "insulin") is typical of patients with non-insulin-dependent diabetes mellitus
      (NIDDM) and is often associated with obesity and hypertension. The elevated
      concentrations detected are indicative not only of insulin but also of its
      immunologically cross-reactive precursors, including proinsulin. Fasting
      hyperinsulinemia appears to be associated with decreased fibrinolytic activity in
      blood, which results from increased activity of plasminogen activator inhibitor
      type-1 (PAI-1), a potential independent risk factor for coronary artery disease.
      Patients who were given proinsulin in a previous clinical study by others
      exhibited an increased incidence of cardiovascular events. Thus, a "proinsulin
      PAI-1 axis" may predispose to coronary thrombosis. To define the possible
      presence of such an axis, this study was designed to determine whether insulin,
      its precursors, or both increase the concentrations of PAI-1 in rabbits in vivo.
      METHODS AND RESULTS: Equimolar proinsulin (n = 10), insulin (n = 11), C-peptide
      (n = 4), or vehicle alone (n = 10) was administered intravenously over 1 hour to
      euglycemic, conscious rabbits. Plasma PAI-1 activity increased 3.8-fold with
      proinsulin (P = .002) and 3.6-fold with insulin (P = .002). By contrast, no
      increase occurred after C-peptide or vehicle was administered. The increased PAI
      1 activity was shown to be attributable to PAI-1 protein by reverse fibrin
      autography. As judged from changes in mRNA in tissues, proinsulin and insulin
      increased PAI-1 gene expression within 3 hours by 2.1- and 2.1-fold,
      respectively, in aorta (P = .025 each) and by 1.9- and 2.4-fold in liver (P =
      .015 and P = .001), with return of values to baseline within 24 hours (n = 4
      experiments in each case). CONCLUSIONS: These results extend our previous
      observations from studies in vitro and suggest that hyperinsulinemia attributable
      to augmented concentrations of proinsulin and insulin in plasma increase plasma
      PAI-1 activity and may contribute to acceleration of atherosclerosis and
      impairment of coronary thrombolysis in patients with NIDDM.

PMID- 7828305
TI  - In vivo evidence of an endothelin-induced vasopressor tone after inhibition of
      nitric oxide synthesis in rats.
AB  - BACKGROUND: Continuous production of nitric oxide (NO) from endothelial cells
      permanently inhibits the synthesis and the vasoconstrictor effects of endothelin.
      Thus, inhibition of NO synthesis might unmask a vasopressor response to
      endothelin. To assess whether endothelin contributes to the pressor response
      induced by inhibition of NO synthesis, we tested whether bosentan, a nonpeptide
      antagonist of ETA and ETB endothelin receptors, affected the hypertensive
      response induced by the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L
      NAME). METHODS AND RESULTS: Anesthetized rats received increasing doses of L-NAME
      (0.1 to 3 mg.kg-1) in the absence or the presence of bosentan (3 mg.kg-1 IV 15
      minutes before L-NAME). Bosentan itself did not affect blood pressure. L-NAME
      induced a dose-dependent increase in mean arterial pressure (percent increase
      from baseline after 3 mg.kg-1, 25 +/- 5%), and this was reduced by bosentan (13
      +/- 3%; P < .05) or by the selective ETA antagonist BQ-123 (3 mg.kg-1: controls,
      25 +/- 4%; BQ-123, 14 +/- 5%; P < .01). In contrast, bosentan did not affect the
      pressor response to phenylephrine (1 to 100 micrograms.kg-1). The response to L
      NAME (3 mg.kg-1) was also reduced by bosentan in ganglion-blocked
      (chlorisondamine 2.5 mg.kg-1: controls, 89 +/- 10%; bosentan, 45 +/- 7%) or
      pithed rats (controls, 165 +/- 9%; bosentan, 85 +/- 12%; P < .01). Bosentan also
      inhibited the pressor response to another inhibitor of NO synthesis, NG-nitro L
      arginine (3 mg.kg-1) in normal (controls, 24 +/- 5%; bosentan, 10 +/- 3%; P <
      .01) or ganglion-blocked (controls, 86 +/- 13%; bosentan, 25 +/- 8%; P < .01)
      rats. Finally, L-NAME induced a modest increase in plasma levels of endothelin-1
      (controls, 26.8 +/- 4.1 pg.mL-1; L-NAME, 38.5 +/- 3.3 pg.mL-1; P < .05).
      CONCLUSIONS: These experiments demonstrate that inhibition of NO synthesis
      unmasks a tonic pressor influence of endothelin, suggesting that this peptide
      could play a major role in pathophysiological situations associated with an
      impaired formation of NO.

PMID- 7828306
TI  - Triggering of plaque disruption and arterial thrombosis in an atherosclerotic
      rabbit model.
AB  - BACKGROUND: It is now recognized that plaque disruption and thrombosis, a process
      often triggered by activities of the patient, is generally the cause of the onset
      of acute coronary syndromes. Understanding of disease onset could be greatly
      enhanced by the availability of a suitable animal model of plaque disruption and
      thrombosis. The aim of this study was to replicate and further characterize an
      atherosclerotic rabbit model of triggering of arterial thrombosis that was
      introduced by Constantinides and Chakravarti more than 30 years ago but not
      subsequently used. Aortic plaques were induced by a high-cholesterol diet, by
      mechanical balloon injury of the artery, or by a combination of the two.
      Triggering was attempted by injection of Russell's viper venom (RVV), which is a
      proteolytic procoagulant, and histamine. METHODS AND RESULTS: A total of 53 New
      Zealand White rabbits were exposed to one of four preparatory regimens: rabbits
      in group I (n = 9) were fed a regular diet for 8 months; rabbits in group II (n =
      13) were fed a diet of 1% cholesterol for 2 months alternated with 2 months of a
      regular diet for a total of 8 months; rabbits in group III (n = 5) underwent
      balloon-induced arterial wall injury, then were given a regular diet for 8
      months; and rabbits in group IV (n = 14) underwent balloon-induced arterial wall
      injury, then were given a diet of 1% cholesterol for 2 months followed by a
      regular diet for 2 months for a total of 4 months. After completion of the
      preparatory regimen, triggering of plaque disruption and thrombosis was attempted
      by injection of RVV (0.15 mg/kg IP) and histamine (0.02 mg/kg IV). In group I,
      normal control rabbits without atherosclerosis, only one small thrombus was noted
      in 1 of 9 rabbits. In group II, cholesterol-fed rabbits, thrombosis occurred in 3
      of 13 rabbits. Thrombus occurred in all rabbits in group III (5 of 5) and in 10
      of 14 rabbits in group IV. Although the frequency of thrombosis was not
      significantly different between groups I and II, possibly due to a small sample
      size, it was significantly different among all four groups (P < .001). Also, the
      frequency and amount of thrombus formation were significantly different among all
      four groups (P < .001; P < .0001) but not between groups I and II. Rabbits with
      atherosclerosis (those in groups II and IV) demonstrated plaque disruption and
      overlying platelet-rich thrombus formation similar to that observed in patients
      with acute coronary syndromes. The surface area covered by thrombus was 2 mm2 in
      group I, 15.3 +/- 19.2 mm2 in group II, 223 +/- 119 mm2 in group III, and 263 +/-
      222 mm2 in group IV. Rabbits in groups III and IV had the greatest amount of
      thrombus, and this amount was significantly greater than in rabbits in groups I
      and II (P < .001 and P < .03, respectively). CONCLUSIONS: A suitable animal model
      is available for the study of plaque disruption and arterial thrombosis.
      Hypercholesterolemia and mechanical arterial wall injury seemed to produce
      plaques vulnerable to triggering of disruption and thrombosis, whereas normal
      arteries were relatively resistant to triggering. This model provides a method to
      evaluate agents that might decrease the occurrence of vulnerable plaques or the
      amount of thrombus formed after triggering. Most important, the model can be used
      to identify the features of vulnerable plaques and the pharmacological stressors
      that trigger plaque disruption and thrombus formation.

PMID- 7828307
TI  - Enhanced intracoronary thrombolysis with urokinase using a novel, local drug
      delivery system. In vitro, in vivo, and clinical studies.
AB  - BACKGROUND: Current pharmacological regimens for treating intracoronary thrombus
      in the cardiac catheterization laboratory generally involve the administration of
      thrombolytic agents that result in a systemic fibrinolytic state and/or require
      prolonged arterial drug infusion. The purpose of the present study was to assess
      a new technique for treating intracoronary thrombus consisting of the local
      infusion of limited quantities of urokinase with a novel drug delivery device.
      METHODS AND RESULTS: THe Dispatch coronary infusion catheter is a new local drug
      delivery system that allows for the prolonged infusion of therapeutic agents at
      an angioplasty site while distal coronary flow is maintained. Three experimental
      protocols were performed to determine the in vitro, in vivo, and clinical
      efficacy of this device. First, in vitro thrombolysis of fresh, porcine thrombus
      trapped in a 4-mm plastic tube with a 50% constriction and perfused with 20%
      porcine plasma was measured. Twenty-three thrombi were weighed before and after
      no treatment (n = 5), "systemic" urokinase administration (n = 4), local infusion
      of 150,000 U urokinase with a standard end-hole catheter (n = 4), local infusion
      of saline with the Dispatch catheter (n = 5), and local infusion of 150,000 U
      urokinase with the Dispatch catheter (n = 5). Second, 25 porcine coronary
      arteries in 23 pigs were dilated in vivo with conventional balloon angioplasty
      and then treated with 123I-labeled urokinase that was administered either by the
      Dispatch catheter (150,000 U; n = 16), intravenous systemic bolus (1,000,000 U; n
      = 3), guiding catheter infusion (500,000 U; n = 3), or local end-hole catheter
      infusion (150,000 U; n = 3). All vessels were subsequently harvested to quantify
      intramural deposition and subsequent washout of urokinase at the angioplasty
      site. Finally, 19 patients with angiographic evidence of intracoronary thrombus
      were treated with local urokinase infusion with the Dispatch catheter either
      before or after balloon angioplasty or directional atherectomy. In vitro studies
      demonstrated that infusion of urokinase with the Dispatch catheter decreased
      thrombus weight by 66% compared with no treatment (-25%), "systemic" urokinase
      administration (25%), end-hole catheter urokinase infusion (32%), or infusion of
      saline by the Dispatch catheter (32%) (P < or = .005). In vivo studies
      demonstrated immediate deposition of 0.12% of the urokinase delivered by the
      Dispatch catheter to the angioplasty site, compared with 0.0007% with systemic
      bolus, 0.003% with guiding catheter infusion, and 0.007% with local infusion with
      an end-hole catheter (P < .001). Urokinase deposited by the Dispatch catheter
      persisted intramurally for at least 5 hours. Patient studies demonstrated
      reduction of thrombus-containing stenoses and complete disappearance of
      intracoronary thrombus in all cases in which 150,000 U urokinase was locally
      infused over 30 minutes. There was no evidence of abrupt closure, distal
      embolization, or no reflow in any patient. CONCLUSIONS: Local urokinase delivery
      with the Dispatch catheter can result in rapid and complete intracoronary
      thrombolysis using substantially less drug than standard thrombolytic techniques.
      Intramural deposition of drug with this technique creates a local reservoir of
      urokinase that may provide prolonged thrombolytic activity at the infusion site.

PMID- 7828308
TI  - Left ventricular performance and remodeling in rabbits after myocardial
      infarction. Effects of a thyroid hormone analogue.
AB  - BACKGROUND: Because the rat postinfarction model differs from human heart failure
      with respect to the composition of myosin heavy chain (MHC) isoforms and other
      contractile proteins, alternative animal models are needed for the development of
      new treatments for human heart failure. The purpose of this study was threefold:
      (1) to test the feasibility of using the V3(beta,beta) rabbit postinfarction
      model for the study of heart failure by characterizing the effects of chronic
      coronary artery occlusion on the left ventricle; (2) to determine whether the
      thyroid hormone analogue 3,5-diiodothyropropionic acid (DITPA) produces
      improvements in left ventricular function; and (3) to determine the effects of
      myocardial infarction and treatment with DITPA on MHC protein isoforms. METHODS
      AND RESULTS: Male New Zealand White rabbits underwent proximal circumflex
      coronary artery ligation. After infarction, rabbits were treated with DITPA (3.75
      mg/kg body wt) or placebo for 21 days and then underwent conscious and open-chest
      hemodynamic studies. In separate groups of rabbits, beta- and alpha-MHC isoforms
      were separated, and relative proportions were measured using gradient sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis and laser densitometry.
      Infarction resulted in increased left ventricular end-diastolic pressure and
      prolonged left ventricular relaxation (tau) (P = .001 for both variables).
      Postinfarction treatment with DITPA decreased left ventricular end-diastolic
      pressure and tau (P = .002 and P = .001, respectively) and increased maximum
      positive and negative dP/dt (P = .002 and P = .016, respectively). Infarcted
      rabbits treated with DITPA had no significant changes in heart rate or left
      ventricular systolic pressure compared with untreated rabbits with infarction.
      There were no significant differences in heart rate, positive dP/dt, peak
      systolic pressure, or tau between sham-operated rabbits and sham-operated rabbits
      treated with DITPA. Although infarction resulted in increased left ventricular
      diameter, there were no effects of DITPA on left ventricular remodeling. Neither
      myocardial infarction nor treatment with DITPA altered the ratio of MHC isoforms.
      CONCLUSIONS: Rabbits that survive occlusion of the circumflex artery will develop
      myocardial dysfunction and left ventricular remodeling. Therapy with DITPA, a
      thyroid hormone analogue, produces improvement in ventricular performance and
      reduces end-diastolic pressure. The hemodynamic effects of DITPA were not
      associated with alterations of MHC isoforms. Whether DITPA represents the
      prototype of a previously undescribed class of agents for the treatment of heart
      failure will need to be determined by clinical trials.

PMID- 7828309
TI  - Effect of enalapril on ventricular remodeling and function during healing after
      anterior myocardial infarction in the dog.
AB  - BACKGROUND: Ventricular remodeling after myocardial infarction involves changes
      in ventricular size, shape, structure, and matrix that impact on function.
      Prolonged angiotensin-converting enzyme inhibition after infarction with
      captopril reduces ventricular enlargement and improves clinical outcome, but
      whether enalapril produces similar benefits is controversial. METHODS AND
      RESULTS: The effect of enalapril during healing between 1 day and 6 weeks after
      myocardial infarction on in vivo changes in ventricular size, shape, mass, and
      function (asynergy, or akinesis and dyskinesis, and ejection fraction), as
      determined by serial two-dimensional echocardiography, hemodynamics, postmortem
      topography (planimetered short- and long-axis ventricular contours), and collagen
      content (determined by levels of hydroxyproline, a marker for collagen), was
      measured in 25 instrumented dogs. The dogs were randomized 1 day after left
      anterior descending coronary artery ligation to a control group (no treatment)
      and a group receiving oral enalapril (2.5 mg BID). Compared with no treatment,
      enalapril produced a sustained lowering of left atrial pressure but no difference
      in heart rate and mean blood pressure over the 6 weeks. Also compared with no
      treatment, enalapril modified in vivo remodeling parameters between 1 day and 6
      weeks, with less elongation of the asynergy-containing segment, a lower expansion
      index (ratio of endocardial lengths of infarct to non-infarct-containing segments
      demarcated by papillary muscle landmarks), less scar wall thinning, a lower
      thinning ratio (ratio of average thickness of infarcted wall to average thickness
      of the normal wall), smaller ventricular volume, less regional bulging and
      aneurysm frequency, prevention of the increase in ventricular mass, less total
      extent of asynergy, and higher volume ejection fraction. At postmortem
      examination, scar mass was similar in the two groups, but topographic maps with
      enalapril revealed less infarct bulging, flatter infarct scars, and less
      noninfarct wall thickness. In addition, postmortem collagen content was similar
      in noninfarct zones of the two groups but lower in infarct zones of the dogs
      given enalapril. CONCLUSIONS: Prolonged enalapril therapy, in a dose that did not
      lower blood pressure, during healing after anterior infarction produced prolonged
      reduction of left ventricular preload in dogs. This diastolic unloading was
      associated with limitation of remodeling parameters (infarct expansion and
      thinning, progressive ventricular dilation and hypertrophy, and regional
      bulging), less total asynergy, and improved left ventricular ejection fraction.
      Although angiotensin-converting enzyme inhibition was associated with lower
      collagen content in the infarct area and altered scar topography, these effects
      did not impact negatively on overall remodeling and function.

PMID- 7828310
TI  - Comparison between 201Tl and 99mTc sestamibi uptake during adenosine-induced
      vasodilation as a function of coronary stenosis severity.
AB  - BACKGROUND: Myocardial uptake of either 201Tl or 99mTc-sestamibi (sestamibi) is
      known to plateau at high coronary flow rates. However, few direct comparisons
      have been made between these tracers to determine what effect differences in the
      uptake plateau for the two tracers may have on the detection of coronary stenoses
      of various severities. METHODS AND RESULTS: Twenty-two dogs were instrumented
      with flow transducers on the left anterior descending (LAD) and circumflex (LCx)
      arteries. In 6 nonstenotic dogs, adenosine was infused directly into the LAD,
      whereas 16 dogs with either critical (n = 7) or mild (n = 9) LAD stenoses
      received an intravenous infusion. At peak flow, 201Tl (0.5 mCi), sestamibi (5 to
      8 mCi), and radiolabeled microspheres were injected simultaneously. Five minutes
      later, dogs were killed, and ex vivo imaging of heart slices and gamma-well
      counting of multiple myocardial samples was performed. Neither 201Tl nor
      sestamibi uptake increased in direct proportion to flow. In the 6 nonstenotic
      dogs, a fivefold increase in LAD flow increased 201Tl and sestamibi uptake by
      only 202 +/- 6% and 138 +/- 4%, respectively (P < .0001). In the dogs with
      critical stenosis, the ratios of stenotic to normal activity by well counting for
      201Tl (0.37 +/- 0.05) and sestamibi (0.53 +/- 0.06) underestimated the
      microsphere-determined flow disparity (0.17 +/- 0.03) (P < .005), but the degree
      of underestimation was greater for sestamibi (P = .001). Similarly, in the dogs
      with mild stenosis, the stenotic-to-normal ratio for 201Tl (0.62 +/- 0.04)
      approximated the flow ratio (0.43 +/- 0.04) better than sestamibi (0.79 +/- 0.03)
      (P < .0001). Sestamibi defects, however, were visually identifiable on the images
      of the myocardial slices. By image quantification, sestamibi defect magnitude
      (LAD-to-LCx count ratio) in the critical stenosis group (0.62 +/- 0.05) was
      significantly less than in the mild stenosis group (0.80 +/- 0.02) (P < .01).
      CONCLUSIONS: Thus, with adenosine-induced hyperemic flow, both 201Tl and
      sestamibi significantly underestimated the magnitude of the flow disparity
      between stenotic and normal perfusion beds. The degree of underestimation was
      greater for sestamibi. The clinical implication of these experimental findings
      for vasodilator perfusion imaging remains to be determined, since factors such as
      greater redistribution and scatter with 201Tl could offset its advantages.

PMID- 7828311
TI  - Detection of coronary stenoses and quantification of the degree and spatial
      extent of blood flow mismatch during coronary hyperemia with myocardial contrast
      echocardiography.
AB  - BACKGROUND: We hypothesized that the degree and spatial extent of blood flow
      mismatch in beds supplied by stenoses that are not flow-limiting at rest can be
      quantified with myocardial contrast echocardiography (MCE) using left atrial (LA)
      and right atrial (RA) injections of contrast during pharmacologically induced
      coronary hyperemia. METHODS AND RESULTS: In 12 open-chest dogs, MCE was performed
      and myocardial blood flow (MBF) was measured by use of radiolabeled microspheres
      at baseline and during phenylephrine-induced coronary hyperemia. In the presence
      of this drug, stenoses were placed during different stages on the left anterior
      descending (LAD) and left circumflex (LCx) coronary arteries, and MCE and MBF
      assessments were performed. LA injections of 2 mL of 0.5 billion/mL microbubbles
      (mean diameter, 4.3 microns) were performed at each stage in all 12 dogs, and RA
      injections of 10 mL of 6 billion/mL microbubbles (mean diameter, 3.7 to 5.3
      microns) were administered in 7 dogs. MCE images in which the contrast disparity
      between the LAD and LCx beds was maximal were digitally subtracted from
      precontrast images, and mean videointensities in these beds were measured after
      the dynamic range of gray-scale intensities was increased in the subtracted image
      and the image was color coded. The region showing hypoperfusion during LAD
      stenosis was planimetered and expressed as a percentage of the myocardial area in
      the short-axis slice. There was an excellent correlation between the LAD/LCx bed
      videointensity ratio and LAD/LCx bed MBF ratio (y = 0.5x + 0.44, r = .91, P <
      .001) during 57 LA injections. There was also an excellent correlation between
      the hypoperfused bed size on MCE during LA injection of contrast in the presence
      of LAD stenosis and the hypoperfused myocardium as determined by radiolabeled
      microspheres (y = 0.8x + 4.2, r = .90, P < .001, SEE = 2.4, n = 11). The anterior
      myocardium was opacified in 6 dogs receiving RA injections of contrast, and the
      hypoperfused area during LAD stenosis correlated closely with that determined by
      radiolabeled microspheres (y = 0.86x + 3.4, r = .93, P < .01). CONCLUSIONS:
      Coronary stenoses, which are not flow limiting at rest, can be detected and the
      degree and spatial extent of blood flow mismatch during pharmacologically induced
      coronary hyperemia can be quantified with MCE using LA and RA injections of
      contrast. Thus, it is possible that the severity of coronary stenoses and the
      quantum of myocardium in jeopardy could be quantified in the future with MCE
      using venous injection of contrast.

PMID- 7828312
TI  - Hyperinsulinemic microalbuminuria. A new risk indicator for coronary heart
      disease.
AB  - BACKGROUND: Both hyperinsulinemia and microalbuminuria have been shown to
      increase coronary heart disease (CHD) risk, but the interaction among
      hyperinsulinemia, microalbuminuria, and the risk for CHD has not been
      investigated in previous studies. METHODS AND RESULTS: The risk of CHD in
      relation to hyperinsulinemia and microalbuminuria was examined in a cohort of
      1069 elderly nondiabetic subjects from Kuopio, east Finland, during 3.5 years of
      follow-up. The overall incidence of CHD death was 2.8%, and 6.9% of study
      subjects died of CHD or had a nonfatal myocardial infarction (later referred to
      as all CHD events). In the highest fasting-insulin quintile (fasting insulin > or
      = 114.0 pmol/L), there was a slightly but insignificantly higher incidence rate
      of both CHD mortality and all CHD events compared with lower quintiles. The
      incidence rates of CHD mortality and all CHD events were significantly higher in
      the highest urinary albumin/creatinine ratio (ACR) quintile (ACR > or = 3.22
      mg/mmol) compared with lower quintiles (P < .05 and P < .01, respectively).
      Hyperinsulinemic microalbuminuria (simultaneous presence of fasting insulin > or
      = 114.0 pmol/L and ACR > or = 3.22 mg/mmol) markedly increased the risk of CHD
      mortality (12.5%, P < .001) and all CHD events (18.8%, P < .001) compared with
      normoinsulinemic subjects without microalbuminuria (2.2% and 5.8%, respectively).
      In univariate logistic regression analyses, hyperinsulinemic microalbuminuria was
      a strong predictor of both CHD death (odds ratio [OR], 5.93; P < .001) and all
      CHD events (OR, 3.39; P = .002). Multivariate logistic regression analyses were
      also performed, including sex, current smoking, waist-hip ratio, systolic blood
      pressure, and HDL cholesterol, with insulin, ACR, or both as independent
      variables. Even after adjustment for these variables, hyperinsulinemic
      microalbuminuria remained a strong predictor of CHD death (OR, 7.91; P < .001)
      and all CHD events (OR, 2.95; P = .014). The group with hyperinsulinemic
      microalbuminuria was characterized by the most adversely affected risk factor
      pattern (high triglycerides > or = 2.3 mmol/L, low HDL cholesterol < or = 0.9
      mmol/L in men and < or = 1.20 mmol/L in women, and hypertension). CONCLUSIONS:
      Simultaneous occurrence of hyperinsulinemia and microalbuminuria identifies a
      group of subjects with a highly increased risk for CHD in elderly nondiabetic
      subjects.

PMID- 7828313
TI  - Metabolic determinants of defibrillation. Role of adenosine.
AB  - BACKGROUND: The single most important determinant of cardiac arrest outcome is
      the duration of ventricular fibrillation (VF) preceding delivery of a high-energy
      shock, because of the adverse effect of VF duration on defibrillation threshold
      (DFT). Although a metabolic mechanism has been proposed, hypoxia, metabolic
      acidosis, or alkalosis do not adversely affect DFT. However, since (1)
      catecholamines and adenosine levels are markedly increased during hypoxia, (2)
      exogenous catecholamines decrease DFT, and (3) adenosine is a potent antagonist
      of the electrophysiological effects of catecholamines on ventricular myocardium,
      we hypothesized that release of adenosine during prolonged VF adversely affects
      DFT and that this effect occurs through an antiadrenergic mechanism. METHODS AND
      RESULTS: DFT was determined in dogs during infusion of adenosine (300
      micrograms.kg-1.min-1) and dipyridamole (0.25 mg/kg), an adenosine uptake
      blocker, a regimen that resulted in adenosine levels in the myocardial effluent
      equivalent to those achieved after 5 minutes of VF. Adenosine increased
      transthoracic DFT in each dog by 49 +/- 14% (n = 21) (mean +/- SEM) and
      transmyocardial DFT in a separate group of 10 dogs by 103 +/- 16%, P = .0003.
      Pretreatment with the specific A1 adenosine receptor antagonist 8
      cyclopentyltheophylline (CPT) 5 mg/kg completely abolished the effects of
      adenosine on DFT. The effects of adenosine on DFT were also examined in the
      denervated state (propranolol 0.2 mg/kg plus bilateral vagotomy). In contrast to
      its effect in the innervated condition, adenosine had no effect on DFT in the
      same dogs when denervated, 49 +/- 11 versus 53 +/- 10 J (P = NS). CONCLUSIONS:
      Adenosine significantly increases transthoracic and transmyocardial DFT, effects
      that are mediated by the A1 adenosine myocardial receptor through an
      antiadrenergic mechanism. These results suggest that enhanced release of
      adenosine during VF may have a deleterious effect on defibrillation and that
      intramyocardial delivery of a specific A1 adenosine antagonist during VF may
      facilitate defibrillation and significantly reduce defibrillation threshold.

PMID- 7828314
TI  - Reconstruction of endocardial potentials and activation sequences from
      intracavitary probe measurements. Localization of pacing sites and effects of
      myocardial structure.
AB  - BACKGROUND: Mapping of endocardial activation is an important procedure for
      diagnosing cardiac arrhythmias and locating the arrhythmogenic site before
      treatment. The objective of the present study was to develop and test a
      mathematical method to reconstruct the endocardial potentials and activation
      sequences (isochrones) from potential data measured with a noncontact,
      intracavitary multielectrode probe (the "inverse problem"). METHODS AND RESULTS:
      A boundary element based mathematical method, combined with a numeric
      regularization technique, was developed for computing the inverse solution.
      Endocardial potentials were computed from intracavitary potentials measured with
      a multielectrode probe placed in the cavity of an isolated, perfused canine left
      ventricle. Data were acquired during rhythms induced by electrical stimuli
      applied at different locations and varying depths within the myocardium.
      Endocardial potentials were measured using intramural needles to evaluate the
      accuracy of the inverse solutions by direct comparison. Inversely computed
      endocardial potentials, from measured probe potentials, reconstruct with good
      accuracy the major features (potential maxima and minima, regions of negative and
      positive potentials) compared with the measured endocardial potentials. During
      early activation, the computed endocardial potentials exhibit a potential minimum
      in close proximity to the pacing site, determining the location of the stimulus
      with good accuracy (within 10-mm error). Multiple stimuli, as close as 10 to 20
      mm to each other, can be distinguished and localized to their sites of origin by
      the inverse reconstruction. Similar to the measured endocardial potentials, the
      spatial distribution of the computed endocardial potentials reflects the
      underlying cardiac fiber direction, and dynamic changes of the computed
      endocardial potentials reflect the rotation of fibers with intramural depth. Maps
      of isochrones show good correspondence between the isochrones determined from the
      computed endocardial potentials and those determined directly from the measured
      endocardial potentials. CONCLUSIONS: Compared with actual, measured endocardial
      potentials and activation sequences, endocardial potential patterns and
      activation sequences can be reconstructed on a beat-by-beat basis from cavitary
      potentials measured with a multielectrode, noncontact probe. The approach
      presented here is shown to reconstruct, with 10-mm accuracy and resolution of 10
      to 20 mm, local events of cardiac excitation (eg, pacing sites). In addition, the
      reconstructed endocardial potentials correctly reflect the underlying fibrous
      structure of the myocardium. These results demonstrate the feasibility of the
      approach. In the experiments, the probe position and endocardial geometry were
      determined invasively. To be clinically applicable, the reconstruction method
      should be combined with a noninvasive method for determining the probe-cavity
      geometry in the catheterization laboratory. It could then be developed into a
      catheter-based technique for locating arrhythmogenic sites and for studying and
      diagnosing conduction abnormalities, reentrant activity, and the effects of drugs
      and other interventions on cardiac activation and arrhythmias.

PMID- 7828315
TI  - Reproducible induction of early afterdepolarizations and torsade de pointes
      arrhythmias by d-sotalol and pacing in dogs with chronic atrioventricular block.
AB  - It has been well established that antiarrhythmic drugs can also have
      proarrhythmic effects such as torsade de pointes (TdP) arrhythmias. It was the
      purpose of this study to create an animal model with a high incidence of
      reproducible TdP that occurs under clinically relevant circumstances. Experiments
      were performed in anesthetized dogs that had been in chronic atrioventricular
      block for 9 +/- 6 weeks. TdP inducibility was attempted using different pacing
      modes before and after the administration of 2 mg/kg d-sotalol. In some
      experiments, endocardial monophasic action potentials were recorded. d-Sotalol
      increased the cycle length of the idioventricular rhythm (1475 +/- 460 to 1730 +/
      570 ms, P < .01) and the QT time (390 +/- 65 to 480 +/- 85 ms, P < .01). In 10%
      of the experiments, spontaneous TdP occurred after d-sotalol. The incidence of
      pacing-dependent TdP was 52% (P < .01). In the inducible group, the cycle length
      of idioventricular rhythm and QT time were significantly longer despite equal
      percentage increases in these parameters after d-sotalol in both groups. The
      pacing modes consisting of more than one frequency change had a higher TdP
      induction rate (P < .05). Reproducibility of TdP induction (three times or more
      using the same pacing train) remained present for approximately 60 minutes after
      d-sotalol and was greater than 90% within the same animal over weeks. TdP
      induction was related to the presence of early afterdepolarizations on the
      monophasic action potential recordings: five of six in the inducible group versus
      two of six in the nonresponders. Inducibility could be further increased to 89%
      when a second bolus of d-sotalol was administered to noninducible dogs. On the
      other hand, decreasing QT time by faster basic pacing or administration of
      isoproterenol, or MgSO4 prevented TdP induction. This effect of MgSO4 coincided
      with the disappearance of early afterdepolarizations. Our animal model shows a
      high incidence of reproducible acquired TdP arrhythmias, allowing study of the
      mechanism and treatment of TdP. TdP induction was related to the combination of a
      slow ventricular rate, the prolongation of QT time, a sudden induced rate change
      that often required two or more cycle length changes, and the presence of early
      afterdepolarizations.

PMID- 7828316
TI  - Current spectrum of cardiogenic shock and effect of early revascularization on
      mortality. Results of an International Registry. SHOCK Registry Investigators.
AB  - BACKGROUND: Cardiogenic shock remains the leading cause of death of patients
      hospitalized with acute myocardial infarction (MI). This study was conducted to
      examine (1) the current spectrum of cardiogenic shock, (2) the proportion of
      patients who are potential candidates for a trial of early revascularization, and
      (3) the apparent impact of early revascularization on mortality. METHODS AND
      RESULTS: Nineteen participating centers in the United States and Belgium
      prospectively registered all patients diagnosed with cardiogenic shock. Two
      hundred fifty-one patients were registered. The mean age was 67.5 +/- 11.7 years,
      and 43% were women. Acute mitral regurgitation or ventricular septal rupture was
      the cause of shock in 8%. Concurrent conditions contributing to the development
      of shock were noted in 5%, and 2% had isolated right ventricular shock. Among the
      remaining 214 patients, nonspecific findings on the ECG associated with
      "nontransmural" MI were seen in 14%. The median time to shock diagnosis after MI
      was 8 hours. The overall in-hospital mortality was 66%. Patients clinically
      selected to undergo cardiac catheterization were significantly younger and had a
      lower mortality than those not selected (51% versus 85%, P < .0001) even if they
      were not revascularized (58%). Mortality for patients undergoing percutaneous
      transluminal coronary angioplasty (PTCA) was 60% (n = 55) and 19% (n = 16) for
      coronary artery bypass graft surgery (CABG). Sixty percent (n = 150) of
      registered patients were judged eligible for a trial of early revascularization.
      Trial-eligible patients were significantly younger (65.4 +/- 11.0 versus 70.6 +/-
      11.9 years, P < .001), had an earlier median time to shock onset after MI (6.5
      versus 17.5 hours, P = .003), and had lower mortality (62% versus 73%, P = .077)
      than ineligible patients. CONCLUSIONS: Patients diagnosed with cardiogenic shock
      complicating acute MI are a heterogeneous group. Those eligible for a trial of
      early revascularization tended to have lower mortality. Patients selected to
      undergo cardiac catheterization had lower mortality whether or not they were
      revascularized. Emergent PTCA and CABG are promising treatment modalities for
      cardiogenic shock, but biased case selection for treatment may confound the data.
      Whether PTCA and CABG reduce mortality and which patient subgroups benefit most
      remain to be determined in a randomized clinical trial.

PMID- 7828317
TI  - A 69-year-old woman with recurrent symptomatic pleural effusions.

PMID- 7828318
TI  - Images in cardiovascular medicine. Unusual complications of aortic valve ring
      abscess in subacute bacterial endocarditis.

PMID- 7828319
TI  - Risk, predicting outcomes, and improving care.

PMID- 7828320
TI  - Clinical trial Data and Safety Monitoring Boards. The search for a constitution.

PMID- 7828321
TI  - Selective loss of microvascular endothelial function.

PMID- 7828322
TI  - Diagnosis of heterotaxy syndrome.

PMID- 7828323
TI  - National Cholesterol Education Program, second report of the Expert Panel on
      detection, evaluation, and treatment of high blood cholesterol in adults.

PMID- 7828324
TI  - Nodoventricular Mahaim pathway concept.

PMID- 7828325
TI  - In vitro stability of N-terminal proatrial natriuretic factor in unfrozen
      samples: an important prerequisite for its use as a biochemical parameter of
      atrial pressure in clinical routine.

PMID- 7828326
TI  - Guidelines for clinical exercise testing laboratories. A statement for healthcare
      professionals from the Committee on Exercise and Cardiac Rehabilitation, American
      Heart Association.

PMID- 7828327
TI  - [Abstracts of the 5th National Symposium of Acupuncture Anesthesia and
      Acupuncture Analgesia, Sept. 20-24, 1994. Wuhan, China].

PMID- 7828328
TI  - GI bleeding: identifying the source.

PMID- 7828329
TI  - Regurgitation in a patient with an esophageal diverticulum.

PMID- 7828330
TI  - Wegener's granulomatosis: changing perceptions of a once-fatal disease.

PMID- 7828331
TI  - Treating Wegener's granulomatosis: how far have we come?

PMID- 7828332
TI  - Antineutrophil cytoplasmic antibodies in Wegener's granulomatosis and other
      diseases: clinical issues.
AB  - BACKGROUND: An association between antineutrophil cytoplasmic antibodies (ANCA)
      and nonimmune complex-mediated glomerulonephritis was first reported over 10
      years ago. In Wegener's granulomatosis, the antibody usually binds proteinase 3.
      Antibodies to a variety of other antigens have been identified in a broad range
      of diseases. SUMMARY: The typical coarse, granular cytoplasmic ANCA pattern on
      indirect immunofluorescence almost always indicates reactivity with proteinase 3,
      whereas the perinuclear ANCA pattern may reflect reactivity with a host of
      different antigens. Antibodies to proteinase 3 are overwhelmingly associated with
      Wegener's granulomatosis (specificity > or = 90%). In a significant number of
      patients, however, disease activity is not linked to an ANCA titer. ANCA may play
      a role in the pathogenesis of many types of inflammatory conditions. Antibodies
      to proteinase 3 may be important in predisposing to Wegener's granulomatosis, but
      definitive in vivo proof of their role is not yet available. KEY POINTS: The
      presence of cytoplasmic ANCA in a patient who is suspected to have Wegener's
      granulomatosis is strong circumstantial evidence in support of that diagnosis.
      However, it does not represent absolute proof and should be viewed with
      skepticism if the clinical presentation is atypical. Conversely, a negative ANCA
      in the setting of a typical presentation should not rule out Wegener's
      granulomatosis. Because ANCA titers may not always vary in tandem with disease
      activity, the decision to modify therapy for Wegener's granulomatosis should
      continue to be based on clinical judgment.

PMID- 7828333
TI  - Wegener's granulomatosis: the man behind the eponym.

PMID- 7828334
TI  - The challenge of drug-resistant tuberculosis.
AB  - CLINICAL ISSUES: After declining for decades, the incidence of tuberculosis is
      again increasing, and strains resistant to multiple drugs are appearing. The
      greatest increases in infection have been in blacks and Hispanics. The disease is
      most aggressive in patients infected with human immunodeficiency virus and in
      patients receiving immunosuppressive therapy; diagnosis may be difficult in these
      groups. Resistance to antituberculosis drugs is the result of inadequate regimens
      or of patients not complying with prescribed regimens. RECOMMENDATIONS: The
      current epidemic can be stopped, but this will require a serious commitment by
      the public, the medical community, government, and industry. Physicians must
      prevent the spread of tuberculosis, detect people who are infected, treat
      infected people preventively with isoniazid, and, in people with active disease,
      rapidly establish the diagnosis and use adequate, directly supervised, four-drug
      regimens to treat it. Convenient combined preparations and programs to directly
      supervise the taking of medications are needed.

PMID- 7828335
TI  - Homocysteine and coronary artery disease.
AB  - BACKGROUND: Homocystinuria is a rare autosomal recessive disease complicated by
      early and aggressive occlusive arterial disease. This may be related to the
      grossly increased homocysteine concentrations seen in this disease. More
      recently, milder hyperhomocysteinemia has been proposed as an independent risk
      factor for coronary artery disease. SUMMARY: Many patients with homozygous
      homocystinuria develop severe premature atherosclerosis and thromboembolism,
      probably caused by abnormally high concentrations of homocysteine. Homocysteine
      undergoes metabolism either by remethylation or transsulfuration, and deficiency
      or dysfunction of any of the substances that regulate these reactions may lead to
      hyperhomocysteinemia. Homocysteine may have adverse effects on platelets,
      clotting factors, and endothelial cells. Studies have demonstrated significantly
      higher plasma homocysteine levels in patients with occlusive arterial disease
      than in controls. The causes are not clearly understood but may include
      deficiency of vitamin B6, vitamin B12, and folic acid and heterozygosity for
      cystathionine synthase deficiency. Vitamin supplementation can lower plasma
      homocysteine levels. CONCLUSIONS: Whether measuring plasma homocysteine levels in
      patients with coronary artery disease should be routine and whether treating
      hyperhomocysteinemia in these patients may reduce the risk of coronary events
      remains to be determined.

PMID- 7828336
TI  - Prevention and osteoporosis management.
AB  - BACKGROUND: Primary osteoporosis affects one in four women over the age of 65 and
      reflects lifelong processes and trends. SUMMARY: Skeletal bone constantly repairs
      the microscopic damage it sustains as a result of the normal activities of
      living. Women achieve their maximum bone density by the close of adolescence.
      Hereditary, nutritional, hormonal, and life-style factors affect the process of
      osteoporosis. Bone densitometry can detect very small deficits long before losses
      become clinically apparent. Intervention can halt osteoporosis at any point and
      perhaps increase bone density, but no known therapy can restore the normal bone
      architecture once it is lost. KEY POINTS: Women should maintain an adequate
      intake of calcium throughout their lifetime, especially during adolescence. Bone
      densitometry at the time of menopause detects preclinical osteoporosis and
      enables physicians to start therapy to preserve the bone structure.

PMID- 7828337
TI  - Physical and social impact of alpha 1-antitrypsin deficiency: results of a
      survey.
AB  - BACKGROUND: Emphysema associated with alpha 1-antitrypsin deficiency can impose
      serious impairment. OBJECTIVE: To gather information about the impact of severe
      alpha 1-antitrypsin deficiency. METHODS: Mail survey, descriptive statistics.
      RESULTS: We sent a survey to 1730 subscribers to a national newsletter, 850 of
      whom had previously stated they had alpha 1-antitrypsin deficiency. A total of
      414 questionnaires were returned; 398 respondents said they had alpha 1
      antitrypsin deficiency, and 300 said they had the PiZZ phenotype. Sixty-six
      respondents who said they had the disease did not know their phenotype. Among the
      304 respondents with severe deficiency, the mean age at the time symptoms first
      appeared was 35.0 years, but the mean age when the disease was diagnosed was 41.3
      years. Overall, 75.3% of respondents with severe deficiency reported at least one
      adverse effect: 44.4% retired early, and 19.1% changed to a physically easier
      job. The duration of diagnostic delay correlated with the degree of adverse
      psychosocial effects. CONCLUSIONS: Alpha 1-antitrypsin deficiency frequently
      escapes diagnosis despite many medical encounters. Affected individuals are often
      unaware of basic details of their disease. Many patients report adverse
      psychosocial effects. Delay in diagnosing this disease is associated with adverse
      psychosocial effects.

PMID- 7828338
TI  - Realistic goals of cancer therapy: effective and humane care.
AB  - BACKGROUND: Cure is the ultimate goal of antineoplastic therapy, but currently
      available treatment falls short of this goal in many situations. OBJECTIVE: To
      present the general aims of antineoplastic treatment and to discuss specific
      examples. SUMMARY: The choice of therapy is influenced by the type of cancer, the
      extent to which it has spread, the effectiveness and toxicity of available
      therapy, the patient's performance status, the presence of symptoms, and the
      patient's preference. Goals of therapy include cure, prolongation of survival,
      improvement in quality of life, palliation of symptoms, and prevention of
      complications. CONCLUSIONS: Establishing the goals of therapy for a patient with
      cancer is an individualized process. Stopping to consider what one is trying to
      accomplish can help the physician give effective and humane care.

PMID- 7828339
TI  - Atrial septal defects.

PMID- 7828340
TI  - Lymphocytic traffic and homing into target tissue and the generation of endocrine
      autoimmunity.
AB  - Endocrine autoimmunity is known to be characterized by the presence of specific
      autoantibodies and from the histopathological point of view by lymphocytic
      infiltration in the target tissue. The presence of mononuclear cell infiltrates
      is the pathological hallmark of most endocrine diseases characterized by an
      autoimmune process directed against antigens expressed on endocrine cells.
      Infiltrating cells can usually be detected by biopsy or by using other, non
      invasive, techniques. However, in endocrine tissue such as the islets of
      Langerhans and the adrenal glands it is difficult to perform biopsies and
      diagnosis of the autoimmune process is dependent mainly upon detection of
      specific autoantibodies. A crucial aspect of endocrine autoimmunity and of all
      processes of organ specific autoimmunity is why and how lymphocytes migrate from
      primary lymphoid tissue to their specific targets. This occurs mainly through
      contact with specific adhesion molecules which enable lymphocytes to adhere to
      the endothelial vessels in close proximity to the target tissue. In this review
      we discuss the homing of peripheral mononuclear cells into target endocrine
      tissues and the mediating role of adhesion molecules.

PMID- 7828341
TI  - Ovarian stromal hypertrophy.

PMID- 7828342
TI  - Ovarian stromal hypertrophy in hyperandrogenic women.
AB  - OBJECTIVE: By using vaginal endosonography, ovarian stromal hypertrophy has been
      shown to be a strong diagnostic feature of polycystic ovarian syndrome and
      related states. However, this sign is difficult to quantify and to correlate with
      other findings because of its subjectivity. We have evaluated the use of computer
      assisted analysis of ultrasound scans to provide more objective measurements of
      ovarian structure and size. DESIGN: We used a computer assisted method for the
      reading of ultrasound scans. It allowed selective calculation of the stromal area
      by subtraction of the cyst area from the total ovarian area on a longitudinal
      ovarian section. PATIENTS: A consecutive series of 57 patients with
      hyperandrogenism (group 1), 17 patients with hypothalamic anovulation (group 2)
      and 20 normal women (group 3). RESULTS: By computerized measure, 75% patients
      from group 1 had a bilateral stromal area above the mean +2 SD (700 mm2) of women
      from group 3. All patients from group 2 were below this threshold. Serum LH level
      was above the normal range in 45% patients from group 1. The stromal area
      correlated positively with the serum delta 4-androstenedione (r = 0.47, P <
      0.005) and 17 alpha-hydroxyprogesterone (r = 0.39, P < 0.005) levels, exclusively
      in group 1. It did not correlate with the basal serum testosterone, LH or insulin
      levels. The cyst area did not correlate with any hormonal parameter. CONCLUSION:
      Ovarian stromal hypertrophy is a frequent and specific feature of
      hyperandrogenism. It correlates with the ovarian androgenic dysfunction. Its
      presence is not always linked with elevated serum immunoreactive LH levels.
      Further data are needed to elucidate the role of insulin and ovarian growth
      factors.

PMID- 7828343
TI  - Luteinizing hormone secretion and hypoandrogenaemia in critically ill men: effect
      of dopamine.
AB  - OBJECTIVE: Critical illness has been associated with decreased LH secretion and
      lowering of testosterone. Dopamine is often used for vasoactive support in these
      patients. We therefore aimed to investigate LH secretion during severe illness
      and particularly the effect exerted by dopamine on LH in such patients. PATIENTS
      AND DESIGN: In a randomized, controlled study of critically ill adult male
      polytrauma patients (n = 9), we evaluated the effect of prolonged (83-296 hours)
      dopamine infusion (5 micrograms/kg/min i.v.) on the dynamics of LH secretion and
      on serum testosterone concentrations. The effect of brief (15-21 hours) dopamine
      administration was documented in an additional randomized, controlled, cross-over
      study involving 6 patients. MEASUREMENTS: Serum LH concentrations were measured
      by IRMA. The LH profiles, obtained by blood sampling every 20 minutes for 9 hours
      during two consecutive nights, were examined by deconvolution analysis. Serum
      testosterone concentrations were measured by RIA once per study night. RESULTS:
      We found that before dopamine initiation and within 24 hours of dopamine
      withdrawal, the mean serum LH concentrations, the LH secretory amplitude, the
      amount of LH secreted per burst, the mean LH secretion rate and the number of LH
      pulses were higher than during dopamine infusion, being increased by a median of
      161% (P = 0.006), 98% (P = 0.03), 106% (P = 0.03), 164% (P = 0.01) and 25% (P =
      0.008) respectively. However, without dopamine administration the amplitude and
      mass of the LH secretory bursts still appeared to be low, whereas the pulse
      frequency remained elevated. After dopamine withdrawal, LH secretion increased
      significantly within 3 hours. Serum testosterone levels were very low and
      dopamine infusion appeared not to affect them within 24 hours. CONCLUSION: We
      documented decreased LH secretory pulse amplitude and mass with increased pulse
      frequency, as well as very low serum testosterone concentrations in critically
      ill men. Dopamine infusion further suppressed LH release by decreasing secretory
      burst amplitude, mass and frequency, possibly through an inhibitory action at
      both the pituitary and the hypothalamic level.

PMID- 7828344
TI  - Androgen suppressive effect of GnRH agonist in ovarian hyperthecosis and
      virilizing tumours.
AB  - OBJECTIVE: Recent studies have suggested that androgen secretion by ovarian
      virilizing tumours may be gonadotrophin dependent. The aim of this study was to
      investigate the suppressive effect of GnRH agonist administration on androgen
      secretion in women with such tumours. DESIGN AND PATIENTS: A single i.m.
      injection of D-Trp-6-GnRH (GnRHa), 3.75 mg, was given to five unrelated patients
      referred for clinical symptoms of virilization with plasma testosterone (T)
      levels greater than 7 nmol/l but with normal dehydroepiandrosterone sulphate
      (DHEAS) levels. Diagnoses of adrenal tumour or a non-classical 21-hydroxylase
      deficiency were screened for by the dexamethasone suppression test, ACTH
      stimulation test and adrenal CT scanning, and were ruled out in all patients. The
      one premenopausal patient received cyproterone acetate in a dose of 50 mg twice
      daily for 3 weeks, starting 1 week before GnRHa administration. MEASUREMENT:
      Testosterone, androstenedione (A), DHEAS, 17-hydroxyprogesterone (OHP), LH and
      FSH plasma concentrations were measured by radioimmunoassay of blood samples
      taken before and 3 weeks after GnRHa. RESULTS: In each patient, GnRHa suppressed
      gonadotrophin levels and reduced T and A to the range for normal control women.
      With these results, and because accurate localization of an ovarian androgen
      secreting tumour could not be achieved by pelvic ultrasonography and CT scanning,
      exploratory laparotomy was undertaken. A Sertoli-Leydig cell tumour was found in
      the premenopausal patient, and granulosa cell tumour, hilus cell tumour and two
      hyperthecoses in the four post-menopausal patients. After bilateral ovariectomy
      and hysterectomy in the post-menopausal woman and after unilateral ovariectomy in
      the premenopausal women, androgen levels were normalized. CONCLUSIONS: In
      virilized women, the findings of increased serum testosterone with normal
      gonadotrophin levels and GnRHa suppression of gonadotrophins leading to
      normalization of testosterone levels, suggest that various ovarian androgen
      secreting tumours, as well as hyperthecosis, are not autonomous but apparently
      depend upon continuous gonadotrophin stimulation.

PMID- 7828345
TI  - Identification of olfactory dysfunction in carriers of X-linked Kallmann's
      syndrome.
AB  - OBJECTIVE: The aim of the study was to test the hypothesis that clinically
      unaffected female carriers of X-linked Kallmann's syndrome have an olfactory
      defect. DESIGN: Assessment of the olfactory threshold to seven standard odorants,
      each at a concentration of 1-10(-8) mol/l. PATIENTS: Five families with X-linked
      Kallmann's syndrome (KS) were tested, containing 19 males with KS, and 9 female
      carriers. Related but unaffected males (n = 8) were used as a control group, and
      in addition seven patients with Turner's syndrome (XO) were assessed.
      MEASUREMENTS: The olfactory threshold was taken as the lowest concentration at
      which each odorant was clearly distinguished from control (liquid paraffin). The
      threshold for each odorant was compared between the subject groups using the non
      parametric Mann-Whitney test. RESULTS: All patients with KS were anosmic to all
      odorants. The female carriers had hyposmia, with a significant reduction in the
      olfactory threshold to putrid, peppermint, floral and pungent odorants compared
      to control subjects, and to peppermint, floral and pungent odorants compared to
      subjects with Turner's syndrome. The latter had olfactory thresholds which were
      statistically identical with the control group. CONCLUSIONS: Obligate female
      carriers of X-linked Kallmann's syndrome are hyposmic compared to control
      subjects. The overlap between the two groups, however, makes olfactory testing
      unreliable as a diagnostic test.

PMID- 7828346
TI  - Two mutations causing vitamin D resistant rickets: modelling on the basis of
      steroid hormone receptor DNA-binding domain crystal structures.
AB  - OBJECTIVE: Hereditary vitamin D resistant rickets (HVDRR) has been shown to be
      due to mutations in the gene encoding the vitamin D receptor (VDR). In two
      patients with the characteristic phenotype we have investigated the functional
      defect and sequenced the VDR cDNA. We report two new mutations in the DNA binding
      domain of the VDR gene and we have used the crystallographic structure of the
      glucocorticoid and oestrogen receptors (GR and ER respectively) as models to
      explain the stereochemical consequences of these mutations. DESIGN: Patient and
      control cell lines prepared from skin fibroblasts were used to measure binding of
      1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and functional responses to this hormone.
      These cells were also used to isolate VDR mRNA from which cDNA was prepared and
      sequenced. VDR cDNA from affected and control patients was also transfected into
      receptor defective cells to analyse further functional responses to 1,25(OH)2D3.
      Computer analysis of mutations in the VDR gene was carried out using the
      glucocorticoid and oestrogen receptors as model systems. PATIENTS: Two patients
      with HVDRR from unrelated families. MEASUREMENTS: Cytosolic binding and nuclear
      association of 1,25(OH)2D3 were determined in control and affected patients, and
      functional response to 1,25(OH)2D3 was assessed by measurement of 25
      hydroxyvitamin D-24-hydroxylase activity (24-hydroxylase). VDR cDNA was sequenced
      and transfected into VDR-deficient CV-1 cells for further analysis of functional
      response to 1,25(OH)2D3 following cotransfection with a chloramphenicol
      acetyltransferase (CAT) reporter plasmid. RESULTS: Cells from HVDRR patients I
      and II showed detectable numbers of VDR with normal hormone binding. However,
      unlike controls, the HVDRR cells did not show induction of 24-hydroxylase
      activity following treatment with 1,25(OH)2D3. Sequencing of cDNA revealed single
      mutations, in patient I (Phe44-->IIe) and in patient II (Lys42-->Glu). Both these
      residues are conserved in the steroid/thyroid hormone receptor superfamily and
      stereochemical analysis has been used to deduce the importance of these amino
      acids and the deleterious effect of these and other mutations in the DNA-binding
      domain of the VDR. CONCLUSIONS: Two new mutations in the vitamin D receptor which
      cause hereditary vitamin D resistant rickets have been described and using
      molecular modelling we have been able to analyse the genesis of this inherited
      disease at the level of stereochemistry.

PMID- 7828347
TI  - Optimal frequency of administration of pamidronate in patients with
      hypercalcaemia of malignancy.
AB  - OBJECTIVE: Hypercalcaemia of malignancy (HM) is a common metabolic complication
      associated with cancer. The hypocalcaemic effects of medications used to reduce
      serum calcium levels in HM are short lived and relapse in hypercalcaemia is not
      uncommon. Pamidronate is one of the most commonly used bisphosphonates in the
      treatment of HM but there are no specific guidelines for the frequency of use of
      this drug in recurrent hypercalcaemia. This study was conducted to assess the
      optimum frequency of pamidronate therapy necessary to maintain normocalcaemia in
      patients with HM. DESIGN AND PATIENTS: Thirty-four patients with HM were randomly
      allocated into two groups and treated with intravenous pamidronate administered
      every 14th or 21st day for 16 weeks (n = 17 each group). Serum calcium and
      urinary hydroxyproline creatinine ratio were measured at weekly intervals.
      RESULTS: The calcium-lowering effect of pamidronate was apparent by 48 hours and
      normocalcaemia was maintained for an average of 15 days. When the drug was
      administered every 3 weeks, hypercalcaemia and associated symptoms developed in
      50% of patients (22 separate episodes) during the 3rd week, before the next dose
      of pamidronate. The incidence of symptomatic hypercalcaemia was significantly
      decreased (10%, 8 separate episodes, P < 0.01) and survival was improved (P <
      0.05) in patients who received pamidronate every 2nd week, thereby minimizing the
      unpleasant and potentially dangerous effects of hypercalcaemia. CONCLUSIONS:
      Intravenous pamidronate 60 mg/dose, administered every two weeks, can maintain
      normocalcaemia in the vast majority of patients with hypercalcaemia of
      malignancy.

PMID- 7828348
TI  - Does acromegaly really predispose to an increased prevalence of gastrointestinal
      tumours?
AB  - OBJECTIVE: The few published prospective studies suggest a strong association of
      colonic tumours with acromegaly, but include small numbers of patients. In
      addition, the upper gastrointestinal tract of these patients has never been
      prospectively studied. The aim of the present study was to investigate the
      incidence of gastric and colonic tumours in a large cohort of acromegalic
      patients. DESIGN: Acromegalic patients consecutively admitted to an Endocrinology
      Department for diagnosis and follow-up, were submitted to gastroscopy and
      colonoscopy, to identify those harbouring gastrointestinal tumours. PATIENTS:
      Over a 5-year period, 54 out of 61 patients (78% with active disease) received
      colonoscopy and 42 out of 61 gastroscopy. No patient had a past history of
      gastrointestinal malignancy. MEASUREMENTS: All polypoid lesions found at
      colonoscopy and gastroscopy were separately recorded and biopsied. RESULTS: No
      case of gastrointestinal cancer or gastric polyp was discovered. Nineteen
      patients (35%) had 1-8 colonic polyps, including 5 (9.3%) with adenomas. When
      compared to patients with a normal colon, those with polyps were significantly
      older (44.5 +/- 14.2 vs 52.1 +/- 10.9 years, P = 0.047), but the duration of
      acromegaly (10.8 +/- 8.4 vs 10.9 +/- 7.1 years, P = 0.9) and the number of
      patients with active disease were similar in both groups. CONCLUSIONS:
      Acromegalic patients do not have an increased incidence of gastric tumours. The
      observed significant variation in the prevalence of colonic adenomas (9-35%, P =
      0.03) and cancer (0-15%, P = 0.017), between our patients and those of the
      published prospective studies with similar demographic characteristics, suggest
      that environmental and hereditary factors may be more important than the presence
      of acromegaly.

PMID- 7828349
TI  - Serum lipoproteins in acromegaly before and 6-15 months after transsphenoidal
      adenomectomy.
AB  - OBJECTIVES: Acromegaly is a rare disorder characterized by over-secretion of GH,
      most often because of a pituitary adenoma. The disease is associated with
      disturbances in lipoprotein metabolism and an increased cardiovascular mortality.
      The aim of the present study was to investigate whether treatment of acromegaly
      results in changes in serum concentrations of lipids and apolipoproteins,
      including lipoprotein(a) (Lp(a)). DESIGN: Fourteen patients with clinical
      features of acromegaly and increased GH secretion were studied 1-10 months before
      and 6-15 months after transsphenoidal adenomectomy in an open study. PATIENTS:
      Three patients had diabetes mellitus before surgery and two of these patients had
      normalized serum glucose levels post-operatively. Mean and baseline plasma GH
      levels were determined from 24-hour GH profiles. Serum samples were taken in the
      morning after an overnight fast. All patients were normocholesterolaemic, and
      four patients were hypertriglyceridaemic before treatment. RESULTS: Mean plasma
      GH levels decreased from 34.5 +/- 7.4 to 2.1 +/- 0.4 mU/l (mean +/- SEM). Serum
      IGF-I, insulin and free T3 levels decreased and serum SHBG concentrations
      increased post-operatively. There was no effect of treatment on serum cholesterol
      concentrations, but serum triglyceride concentrations decreased. Serum
      apolipoprotein (apo) B and apoE levels were unaffected by treatment. Serum apoA-I
      levels increased and Lp(a) levels decreased post-operatively. CONCLUSIONS:
      Successful treatment of acromegaly, resulting in normal mean GH values (< 5 mU/l)
      and/or normal responsiveness to TRH, have beneficial effects on serum
      lipoproteins with increased serum apoA-I levels and decreased serum levels of
      triglycerides and Lp(a). These effects seem to be independent of improvement in
      glucose tolerance, since patients with diabetes mellitus before surgery and
      normal fasting blood glucose levels post-operatively had similar lipoprotein
      responses to treatment as those with normal fasting blood glucose levels before
      surgery.

PMID- 7828350
TI  - Growth hormone administration stimulates energy expenditure and extrathyroidal
      conversion of thyroxine to triiodothyronine in a dose-dependent manner and
      suppresses circadian thyrotrophin levels: studies in GH-deficient adults.
AB  - OBJECTIVE: The impact of exogenous GH on thyroid function remains controversial
      although most data add support to a stimulation of peripheral T4 to T3
      conversion. For further elucidation we evaluated iodothyronine and circadian TSH
      levels in GH-deficient patients as part of a GH dose-response study. PATIENTS:
      Eight GH-deficient adults, who received stable T4 substitution due to central
      hypothyroidism; two patients, who were euthyroid without T4 supplementation were
      studied separately. DESIGN: All patients were initially studied after at least 4
      weeks without GH followed by 3 consecutive 4-week periods in fixed order during
      which they received daily doses of 1, 2 and 4 IU of GH/m2 body surface area. The
      patients were hospitalized for 24 hours at the end of each period. MEASUREMENTS:
      Circulating total and free concentrations of T4 and T3, total rT3 and TSH were
      measured once at the end of each study period. Circadian TSH levels were recorded
      during the period without GH and during GH treatment with 2 IU GH. RESULTS:
      Highly significant GH dose-dependent increases in total and free T3 and a
      reduction in rT3 were observed. The T3/T4 ratio also increased with increasing GH
      dosages (P < 0.001). In seven patients subnormal T3 levels were recorded in the
      period off GH, despite T4 levels well within the normal range. Resting energy
      expenditure also increased and correlated with free T3 levels (r = 0.47, P <
      0.05). The circadian TSH levels exhibited a significant nocturnal increase during
      the period without GH, whereas GH therapy significantly suppressed the TSH levels
      and blunted the circadian rhythm (mean TSH levels (mU/l) 0.546 +/- 0.246 (no GH)
      vs 0.066 +/- 0.031 (2 IU GH) (P < 0.05)). The two euthyroid non-T4 substituted
      patients exhibited qualitatively similar changes in all parameters. CONCLUSIONS:
      GH administration stimulated peripheral T4 to T3 conversion in a dose-dependent
      manner. Serum T3 levels were subnormal despite T4 substitution when the patients
      were off GH but normalized with GH therapy. Energy expenditure increased with GH
      and correlated with free T3 levels. GH caused a significant blunting of serum
      TSH. These findings suggest that GH plays a distinct role in the physiological
      regulation of thyroid function in general, and of peripheral T4 metabolism in
      particular.

PMID- 7828351
TI  - Short and long-term cardiovascular effects of growth hormone therapy in growth
      hormone deficient adults.
AB  - OBJECTIVE: Since GH substitution therapy is now available for adult GH deficient
      patients, information on the cardiovascular effects of GH substitution has
      assumed major clinical interest. We have therefore assessed cardiovascular
      effects of short and long-term growth hormone substitution therapy in these
      patients. PATIENTS AND MEASUREMENTS: Doppler echocardiography was performed in 21
      GH deficient patients after 4 months placebo and 4 months GH therapy, in a double
      blind cross-over study. In an open design study, 13 patients were reinvestigated
      following 16 months and 9 patients following 38 months of GH therapy. Twenty-one
      age and sex-matched normal control subjects were also investigated. RESULTS:
      Heart rate was increased in placebo treated patients as compared to controls.
      After 4 months of GH treatment, heart rate showed a further increase (10%, P <
      0.01) and seemed to remain elevated after 16 months of GH therapy. Systolic and
      diastolic blood pressures were significantly lower in placebo treated patients
      than in controls, and did not change significantly after GH treatment. The left
      ventricular diastolic diameter was reduced in patients as compared to controls,
      but increased after 4 months GH therapy (P > 0.05) and seemed to increase further
      during prolonged GH treatment. Cardiac index was at the same level in controls
      and in placebo-treated patients, but increased by 20% following GH therapy and
      remained elevated after 16 and 38 months (P < 0.05) of GH substitution.
      CONCLUSION: Following GH substitution in GH deficient adult patients, left
      ventricular diastolic dimensions increased and seemed to normalize, while heart
      rate and cardiac output were found to be increased to supranormal levels.

PMID- 7828352
TI  - Endogenous and stimulated GH secretion, urinary GH excretion, and plasma IGF-I
      and IGF-II levels in prepubertal children with short stature after intrauterine
      growth retardation. The Dutch Working Group on Growth Hormone.
AB  - OBJECTIVE: The pathophysiological mechanisms underlying the failure of catch up
      growth in children with short stature after intrauterine growth retardation
      (IUGR) remain obscure. Since GH secretion disturbances might play a role in the
      growth retardation of these children we have investigated various aspects of the
      GH/IGF axis. DESIGN: Cross-sectional study in one group of patients. PATIENTS:
      Forty prepubertal children (15 girls/25 boys; mean age (range) 7.5 years (3.4
      10.8)) with short stature (height below the third centile) after IUGR, defined as
      a birth length below the third centile for gestational age, were studied.
      MEASUREMENTS: GH secretion was determined by a 24-hour plasma GH profile
      (sampling every 20 minutes) and, on a separate occasion, by a standard arginine
      provocation test (ATT). Plasma IGF-I and IGF-II levels were measured at the start
      of the GH profile. Urine was collected to measure urinary GH levels. Plasma and
      urinary GH were determined by double antibody RIA. IGF-I and IGF-II were
      determined by specific RIA after acid chromatography. The 24-hour GH profiles
      were analysed using Pulsar. RESULTS: Endogenous GH secretion was similar for boys
      and girls. Boys had significantly lower mean GH levels compared to healthy
      controls. Forty per cent of the children met our criteria for a normal 24-hour GH
      profile (group A; n = 16) and 60% (n = 24) did not. We subdivided these 24
      children into two groups: group B (n = 14) (children with either mean GH levels
      less than controls but with at least one spontaneous GH peak above 20 mU/l and
      children with normal mean GH levels but with no GH peak above 20 mU/l (subnormal
      24-hour GH profile)) and group C (n = 10) (children with mean GH levels less than
      controls and no GH peak above 20 mU/l (low 24-hour GH profile)). The GH secretory
      abnormalities were due to a decrease in pulse amplitude, not in pulse frequency.
      Mean (SD) maximal GH response during ATT was 22.3 (12.1) mU/l. Nineteen children
      (47.5%) had a maximal GH value < 20 mU/l. Moderate, but significant, correlations
      were found between several 24-hour GH profile characteristics and the maximal GH
      response during ATT (r = 0.31-0.35; P < 0.05). Mean (SD) overnight urinary GH
      excretion was 3.8 (2.1) and 4.4 (3.5) microU/night for boys and girls,
      respectively. Compared to healthy schoolchildren, overnight urinary GH was lower
      in boys, but not in girls. Mean (SD) IGF-I and IGF-II SDS levels for
      chronological age were -0.88 (1.40) and -0.64 (1.48), respectively. Plasma IGF-I
      and IGF-II levels were significantly reduced compared to controls. Height SDSCA
      or height velocity SDSCA did not correlate with either spontaneous or stimulated
      GH secretion, urinary GH excretion or plasma IGF-I or IGF-II levels. CONCLUSIONS:
      Our study indicates that 50-60% of children with short stature after intrauterine
      growth retardation have 24-hour GH profile abnormalities and/or subnormal
      responses to arginine provocation, while mean plasma IGF-I and IGF-II levels are
      significantly reduced, indicating GH insufficiency. Urinary GH excretion is lower
      in boys, but not in girls. The precise mechanism of the failure to catch up
      growth needs further elucidation. It seems justified to start clinical trials in
      order to investigate whether treatment with exogenous GH might be beneficial for
      these children.

PMID- 7828353
TI  - The effect of growth hormone replacement on cortisol metabolism and
      glucocorticoid sensitivity in hypopituitary adults.
AB  - OBJECTIVE: Growth hormone (GH) replacement therapy in hypopituitary adults is
      associated with sodium and water retention. The underlying mechanisms are
      incompletely understood and a possible contribution of altered cortisol
      metabolism or action has not been evaluated. We have investigated the effect of
      GH replacement therapy on cortisol metabolism, cortisol binding globulin and in
      vitro glucocorticoid sensitivity in a group of adult hypopituitary patients.
      DESIGN AND PATIENTS: We studied 19 adult hypopituitary patients (18 adult onset,
      M:F, 6:13), who were receiving conventional hydrocortisone (16 patients),
      thyroxine (14 patients), triiodothyronine (1 patient), sex steroid (9 patients),
      human chorionic gonadotrophin (1 patient) or desmopressin (6 patients)
      replacement during a 6-month, double blind controlled trial of GH therapy
      (active:placebo, 8:11) followed by a 6-month open phase of GH (mean dose: 0.2
      IU/kg/week, range 0.051-0.27) and after a 6-week washout phase following
      discontinuation of GH therapy. MEASUREMENTS: Twenty-four-hour urine free
      cortisol, cortisol metabolites (CoM), ratio 11-hydroxy/11-oxo CoM (F/E) and ratio
      5 alpha/beta tetrahydrocortisol were measured at 6 months, 12 months and after
      the 6 week washout phase. Serum cortisol binding globulin was measured basally,
      at 6 months, 12 months and after washout. Glucocorticoid sensitivity was
      determined in lymphocyte preparations from 8 patients, during GH therapy and
      after washout, using an in-vitro technique dependent on dexamethasone suppression
      of phytohaemagglutinin-stimulated thymidine incorporation into DNA. Plasma renin
      activity and aldosterone were measured after 6-12 months GH therapy and after
      washout. RESULTS: After 6 months of GH, in patients on hydrocortisone (n = 9),
      there were significant decreases in CoM (mean decrement 21%, P < 0.01), F/E (mean
      decreased from 1.27 to 1.0, P = 0.04; reference range 0.33-1.29) and 5 alpha/5
      beta tetrahydrocortisol (mean decreased from 0.67 to 0.48, P = 0.01) and a
      subsequent increase after washout. Patients not on hydrocortisone (n = 2)
      demonstrated a normal basal F/E falling by 25% on GH therapy but no change in
      CoM. During 12 months of GH therapy, patients on hydrocortisone (n = 7)
      demonstrated a further trend to decrement in CoM (P = 0.09) which reversed after
      washout (P = 0.04). Urine free cortisol tended to fall during GH therapy and
      increased significantly following washout after 12 months treatment (P < 0.02).
      Serum cortisol binding globulin decreased by 20% (P < 0.05) during 12 months GH
      treatment but remained within the reference range. In-vitro studies demonstrated
      a trend to reduced glucocorticoid sensitivity on GH therapy; the maximum
      inhibition of phytohaemagglutinin by dexamethasone tended to be less on GH
      therapy (P = 0.052) and was also lower than in 29 normal volunteers (P < 0.05).
      There were no significant changes in plasma renin but there was a small increment
      in aldosterone in recumbent patients (P = 0.04) during the open phase of GH
      therapy in the placebo arm. CONCLUSIONS: GH therapy in hypopituitary adults is
      associated with an apparent reduction in availability of administered
      hydrocortisone as measured by urine cortisol metabolites and urine free cortisol.
      This effect is unlikely to be clinically significant except possibly in ACTH
      deficient subjects on suboptimal hydrocortisone replacement. The changes in F/E
      suggest that GH may directly or indirectly modulate the activity of 11 beta
      hydroxysteroid dehydrogenase. The apparent decrease in glucocorticoid sensitivity
      during GH therapy, demonstrated in vitro, merits further investigation.

PMID- 7828354
TI  - Inhibition of growth hormone release after the combined administration of GHRH
      and GHRP-6 in patients with Cushing's syndrome.
AB  - OBJECTIVE: In patients with Cushing's syndrome there is a blunted GH response to
      all types of stimuli. Although inferential data point towards a direct
      perturbation in the pituitary exerted by glucocorticoids, the basic mechanism is
      unknown. His-D-TRP-ALA-TRP-D-Phe-Lys-NH2 (GHRP-6) is a synthetic hexapeptide
      which releases GH by a direct pituitary effect through receptors other than GHRH
      receptors. Furthermore, the combined administration of GHRH and GHRP-6 is able to
      induce a large GH discharge even in some pathological states such as obesity,
      associated with GH blockade. To gain further insight into the disrupted
      mechanisms of GH secretion, Cushing's syndrome patients were challenged with
      either GHRH, GHRP-6 or GHRH together with GHRP-6. A group of normal subjects was
      included for control purposes. DESIGN: Three different tests were undertaken: (a)
      GHRH 100 micrograms i.v.; (b) GHRP-6 100 micrograms i.v. and (c) GHRH plus GHRP-6
      100 micrograms i.v. of each; administered to each subject on different days, at
      least 4 days apart. PATIENTS: Ten patients (8 women, 2 men) with untreated
      Cushing's syndrome, 9 Cushing's disease and 1 adrenal adenoma. Five healthy
      volunteers (3 women, 2 men) of similar ages served as a control group.
      MEASUREMENTS: Plasma GH levels were measured by immunoradiometric assay. RESULTS:
      The areas under the curve (AUC) of GH secretion (mean +/- SEM in mU/I/120 min) in
      the control subjects after each test were: GHRH, 1420 +/- 330; GHRP-6, 2278 +/-
      290 and GHRH plus GHRP-6, 7332 +/- 592 (P < 0.05 vs each compound alone). The
      AUCs for Cushing's syndrome patients were: GHRH, 248 +/- 165; GHRP-6 530 +/- 170
      and for GHRH plus GHRP-6, 870 +/- 258 (P < 0.05 vs GHRH alone). After the
      combined stimulus only one out of the ten patients with hypercortisolism showed a
      GH peak over 20 mU/I, while all the controls had a peak over 84 mU/I.
      CONCLUSIONS: GHRP-6 induced GH secretion as well as the GH discharge elicited by
      GHRH and GHRP-6 are considerably reduced in Cushing's syndrome patients. This
      suggests that the main impairment of GH secretion in that pathological state
      resides at pituitary level.

PMID- 7828355
TI  - An audit of selected patients with non-functioning pituitary adenoma treated by
      transsphenoidal surgery without irradiation.
AB  - OBJECTIVE: To determine whether the rate of tumour regrowth in patients with non
      functioning pituitary tumour treated by transsphenoidal surgery and selected for
      observation without post-operative irradiation is acceptably low, and to identify
      a group of patients who could appropriately avoid pituitary irradiation.
      SUBJECTS: One hundred and thirty-two patients treated by transsphenoidal surgery,
      of whom 98 did not undergo post-operative irradiation. These 98 were selected as
      having had apparently complete surgical removal, and as lacking features of
      tumour invasion or rapid growth; 73 of them are being followed by serial
      pituitary imaging to detect tumour regrowth. RESULTS: Forty-two patients who have
      been imaged on two or more occasions or more than two years after operation have
      shown no sign of tumour regrowth; 25 of them have been imaged at 3 or more years
      after operation, 13 at more than 5 years, and 4 at more than 10 years. Eight
      patients have shown regrowth as judged by imaging, although only one had pressure
      symptoms at the time; 5 out of 6 of these recurrences were found within 5 years
      of operation (two cannot be timed). The unirradiated group of 73 patients showed
      90% recurrence-free survival at 5 years (95% confidence limits 80-100%).
      CONCLUSIONS: Provided that careful surgery and meticulous recall mechanisms for
      imaging can be ensured, patients so selected may be given the information
      contained in these results and offered the choice of follow-up by imaging alone,
      without pre-emptive irradiation. We recommend that they should be imaged 6-8
      weeks post-operatively, then at either 6 or 12 months depending on the
      appearance, and then every 3-5 years for at least 15 years. By this means, many
      patient-years of good health and relative medical independence can be gained,
      together with some financial saving.

PMID- 7828356
TI  - Abnormal response of luteinizing hormone beta subunit to thyrotrophin-releasing
      hormone in patients with non-functioning pituitary adenoma.
AB  - OBJECTIVE: It has been suggested that the response of free beta-subunit of LH (LH
      beta) to TRH is the most useful in-vivo marker of gonadotroph adenomas in
      patients with non-functioning pituitary adenomas (NFPA). The aim of the present
      study was to investigate LH beta secretion in patients with NFPA in whom other
      markers of gonadotroph adenomas, such as supranormal basal concentrations or
      responses of intact gonadotrophins to TRH, were absent. DESIGN AND PATIENTS:
      Serum basal levels of LH beta LH and FSH were evaluated in 80 patients with NFPA
      showing normal levels of intact gonadotrophin, 20 with PRL-secreting adenomas, 25
      with GH-secreting adenomas and 58 healthy subjects. Moreover, LH beta, LH, FSH
      and alpha-subunit (alpha-SU) were evaluated in 27 patients with NFPA in whom
      intact gonadotrophin responses to TRH were absent, 8 with PRL-oma, 7 with GH-oma
      and 17 healthy subjects before and 20, 30 and 60 minutes after the intravenous
      administration of either 200 micrograms TRH or placebo. A response was considered
      present when serum LH beta increased by at least 50% above basal levels.
      MEASUREMENTS: LH beta was evaluated using a new assay based on the sequestration
      of the combined and free alpha-SU by an anti alpha-SU biotinylated monoclonal
      antibody (MAb) and the subsequent measurement of the LH beta by an IFMA method
      employing two MAbs directed towards two different epitopes on LH beta. Intact LH
      and FSH were assayed with an IFMA method and alpha-SU with an IRMA method.
      RESULTS: In basal conditions, no significant difference in the mean values of LH
      beta was observed among patients with different types of tumour and normal
      controls. In 9 of 27 (33%) patients with NFPA, TRH caused an abnormal elevation
      of serum LH beta (net increase 410 +/- 403%, range 71-1300) which was completely
      dissociated from changes in intact gonadotrophins. Of the 5 patients who had a
      TRH test repeated after transsphenoidal surgery, abnormal LH beta responses
      disappeared in 2 and were maintained in 3. Disappearance of LH beta response
      occurred only in patients in whom improvement of visual field and radiological
      imaging after adenomectomy was observed. In contrast, in all patients with
      pituitary tumours other than NFPA and healthy subjects a response to TRH was
      absent (net increase ranging from 0 to 23%). Immunofluorescence, performed on 14
      NFPA removed from patients either responsive or unresponsive to TRH, showed a
      variable proportion of cells positive for LH beta, without a significant
      difference between the two groups. CONCLUSIONS: These results indicate that
      measurement of basal LH beta is of poor value in the diagnosis of non-functioning
      pituitary adenomas and the identification of gonadotroph adenomas among non
      functioning pituitary adenomas. Conversely, an abnormal response of free LH beta
      to TRH occurs in about a third of patients with low/normal basal gonadotrophins
      unresponsive to TRH stimulation.

PMID- 7828357
TI  - Evidence for the effect of antibodies to TSH receptors on the thyroid
      ultrasonographic volume in patients with Graves' disease.
AB  - OBJECTIVE: It has been demonstrated that antibodies (Ab) to thyroid-stimulating
      hormone receptors (R), which stimulate the thyroid gland, induce hyperthyroidism
      in patients with Graves' disease. Furthermore, it has been shown in thyroid cells
      in culture that thyroid-stimulating hormone receptor Ab acts through the
      adenosine 3', 5'-monophosphate pathway which stimulates both thyroid
      hormonogenesis and growth. We investigated the relations between thyroid
      autoimmunity expression and thyroid ultrasonographic parameters or thyroid
      hormonal status in patients with Graves' disease. PATIENTS: A prospective study
      of 53 consecutive patients referred with untreated Graves' disease. MEASUREMENTS:
      Measurements were made of serum TSH-R, peroxidase (TPO) and thyroglobulin (Tg) Ab
      and basal plasma free T4 (FT4), free T3 (FT3) and TSH. Thyroid morphological
      characteristics (number and total volume of nodule(s), total volume of lobes and
      total thyroid volume) were determined by ultrasonography. RESULTS: There were
      significant correlations (P < 0.001) between TSH-RAb levels and FT4 values (r =
      0.48) or FT3 levels (r = 0.46). Likewise, significant correlations were found
      between TSH-RAb levels and total lobe volume values (r = 0.56, P < 0.001), total
      nodular volume values (r = 0.59, P < 0.01) or total thyroid volume values (r =
      0.63, P < 0.001). By contrast, no correlation was found between TSH-RAb levels
      and the number of nodules or between any of the ultrasonographic parameters and
      TPOAb levels or TgAB values. CONCLUSIONS: This study demonstrates, in vivo, that
      TSH receptor antibodies modulate the thyroid ultrasonographic extranodular and
      nodular volumes in patients with Graves' disease.

PMID- 7828358
TI  - Turner's syndrome with X-isochromosome and Hashimoto's thyroiditis.
AB  - OBJECTIVE: The higher frequency of Hashimoto's thyroiditis in Turner's syndrome
      compared with the general population is well known. We have attempted to
      establish clearly the more frequent association of thyroiditis with the X
      isochromosome, since previous reports of this aspect have included only small
      numbers of patients. DESIGN: Retrospective study of patients with Turner's
      syndrome investigated within the past 12 years. PATIENTS: Sixty-seven cases of
      Turner's syndrome were reviewed. MEASUREMENTS: Peripheral blood leucocyte
      karyotype and screening for thyroid disturbances on the basis of clinical
      examination and laboratory evaluation (anti-thyroglobulin and anti-microsomal
      antibodies, basal TSH levels and TSH levels after TRH stimulation) were made for
      each patient. RESULTS: A diagnosis of thyroiditis, based on the association of
      positive antibody titres, elevated TSH and an abnormal thyroid gland on clinical
      examination, was established in 20.9% (14/67) of cases. A significantly higher
      frequency of thyroiditis was found among the patients presenting with an X
      isochromosome (57.3%, 9/16), compared to patients with other karyotypes (9.8%,
      5/51) (P = 0.0001). CONCLUSIONS: Our results, obtained by investigation of a
      larger number of patients with an X-isochromosome karyotype than in previous
      reports, confirm conclusively that patients with X-isochromosome Turner's
      syndrome have an increased risk of developing thyroiditis.

PMID- 7828359
TI  - Corticotrophin-releasing factor immunostaining is present in placenta and fetal
      membranes from the first trimester onwards and is not affected by labour or
      administration of mifepristone.
AB  - BACKGROUND AND OBJECTIVES: Corticotrophin releasing factor (CRF) is present in
      the human placenta and fetal membranes. Placental CRF content and plasma CRF
      concentrations rise throughout gestation and fall rapidly after delivery. The
      regulation of CRF production from the placenta is poorly understood. The
      objective of this study was to use the antiprogestin, mifepristone, to determine
      whether progesterone has a regulatory effect on CRF production in the first
      trimester of pregnancy. PATIENTS: Women undergoing first trimester (gestation 5
      12 weeks) therapeutic abortion (by suction curettage with and without the
      synthetic PGE1 analogue, gemeprost (16,16-dimethyl-trans-delta 2-PGE1 methyl
      ester) vaginally 2-4 hours prior to the procedure; or with 600 mg mifepristone 48
      hours prior to receiving 1 mg gemeprost vaginally), second trimester therapeutic
      abortion (600 mg mifepristone, 1 mg gemeprost), in association with preterm
      delivery (gestation 25-34 weeks) and at term (gestation 35-42 weeks) by
      spontaneous delivery, induced labour or elective Caesarean section. MEASUREMENTS:
      Immunohistochemical localization of CRF and quantification of CRF content by
      radioimmunoassay of tissue extracts, in human placenta and fetal membranes.
      RESULTS: CRF was immunolocalized to the syncytiotrophoblast cells of the placenta
      at all stages of gestation from 5 to 42 weeks. In the fetal membranes CRF
      immunoreactivity was localized in the epithelial and subepithelial cells of the
      amnion, some cells of the reticular and cellular layers of the chorion, and in
      decidual stroma. This pattern was seen in all tissues studied. Pretreatment with
      prostaglandins, mifepristone or both during the first trimester did not alter the
      distribution or the intensity of the CRF immunostaining. Placental CRF content
      rose throughout gestation but, consistent with the immunostaining results, was
      unaffected by the administration of mifepristone or by labour. CONCLUSIONS: CRF
      is localized in the syncitiotrophoblast cells of the placenta and is clearly
      present early in the first trimester of pregnancy. The lack of an effect of
      mifepristone or mode of delivery suggests that syncytiotrophoblast produces CRF
      constitutively throughout pregnancy.

PMID- 7828360
TI  - Hyperthyroidism associated with metastatic thyroid carcinoma.
AB  - We report a patient with unilateral thyroid carcinoma, who developed
      hyperfunction of the thyroid gland during the metastatic progression of the
      thyroid carcinoma. Concurrently with this event, TSI increased and it is
      suggested that the differentiated aggressive metastatic thyroid neoplasm had
      initiated the autoimmune disorder leading to TSI production and thus to
      hyperplasia and hyperfunction of the thyroid resulting in hyperthyroidism.

PMID- 7828361
TI  - Growth hormone deficiency coupled with hypogonadism in AIDS.
AB  - Both growth hormone and sex steroid deficiencies are known to affect quality of
      life adversely. Hypogonadism is not infrequent in patients with AIDS and due
      mostly to hypothalamic or end-organ failure. The prevalence of GH deficiency is
      unknown. We report two cases of GH deficiency in AIDS, one of which was
      associated with gonadotroph failure. The significance of GH deficiency in HIV
      infection in terms of its potential effects on disease progression is discussed.
      Further studies are required to assess the prevalence of GH deficiency and to
      clarify its role in the immunopathogenesis of AIDS.

PMID- 7828362
TI  - Metyrapone test for hypothalamic-pituitary-adrenocortical function.

PMID- 7828363
TI  - Pituitary apoplexy following the administration of gonadotrophin releasing
      hormone.

PMID- 7828364
TI  - Anti-cardiolipin antibodies in autoimmune thyroid disease.

PMID- 7828365
TI  - Differential transcription elements direct expression of HLA-DQ genes.
AB  - Regulation of class II MHC gene expression, including the HLA-DQ genes, is
      primarily at the level of transcription. Locus-specific control of DQ gene
      transcription is both tissue-specific and developmentally regulated and relies on
      complex mechanisms involving specific DNA-protein interactions. Electrophoretic
      mobility shift and DNase I protection assays demonstrate the presence of unique
      nuclear protein interactions with the consensus W and Y box elements in the DQB1
      promoter region in DQ-negative cell lines. Based on these and other recent
      studies, a multistage model of DQ gene regulation is outlined to account for
      specific patterns of DQ gene expression.

PMID- 7828366
TI  - Development of oral vaccines to stimulate mucosal and systemic immunity: barriers
      and novel strategies.
AB  - Many questions regarding the induction of mucosal and humoral immunity through
      oral vaccination exist. Efficacy is dependent on the physicochemical properties
      of the antigen, the gastrointestinal environment, the presence of adjuvants, and
      the mode of delivery. Understanding how these factors interrelate will be
      critical to the development of new oral vaccines. A number of approaches are
      currently being studied to enhance the immune response. These include chemical
      conjugation, immunization with recombinant bacteria and viruses, and mucosal
      adjuvants. Vaccine delivery systems prepared from natural or synthetic polymers
      is a particularly promising area because many of the current methods to induce
      mucosal stimulation can be incorporated within these systems. Thus, the polymeric
      delivery system functions as a platform to facilitate uptake by M-cells and
      prolong antigen presentation and stimulation of the Peyer's patches. This Review
      examines some of the physiological and immunological barriers associated with
      oral vaccination and discusses novel strategies to overcome such barriers.

PMID- 7828367
TI  - Characterization of in vivo mutated T cell clones from patients with systemic
      lupus erythematosus.
AB  - Patients with systemic lupus erythematosus (SLE) have increased percentages of
      activated T cells and increased numbers of cells with mutations in their
      hypoxanthineguanine phosphoribosyltransferase (hprt) gene, as judged by growth in
      the presence of 6-thioguanine. To study the relevance of these mutant T cells to
      disease pathogenesis, we have assessed the phenotype and functional capabilities
      of such cells from 21 patients with SLE who never had received cytotoxic drugs.
      The frequency of T cells with mutations in hprt in the blood of these patients
      ranged from normal to 25 times normal (mean +/- SEM [21.1 +/- 6.1] x 10(-6)
      versus [4.8 +/- 0.8] x 10(-6), in 15 age-matched normal individuals, P < 0.001)
      and correlated significantly with disease duration. CD4+ and CD8+ phenotypes were
      comparable among mutated and nonmutated clones from both patients and normals.
      Although the frequency of CD3+CD4-CD8- cells was low, it was increased among SLE
      derived T cells (mutated and wild-type) compared with clones derived from normals
      (5% for SLE vs 1% for normals). A substantial percentage of all clones were able
      to help autologous B cells to produce anti-ssDNA, 11 of 68 (16%) selected clones
      and 3 of 28 (11%) nonselected clones. Help for autoantibody production was
      confined to CD4+ SLE-derived T cell clones. It could be blocked using an anti-HLA
      DR mAb, suggesting that classical cognate help was operative. This represents the
      first estimate of the frequency of T cells able to drive autoantibody production
      in SLE.

PMID- 7828368
TI  - Immunological function in post-traumatic splenosis.
AB  - A 28-year-old male medical student underwent splenectomy at 8 years of age due to
      traumatic rupture of the spleen sustained in a motor vehicle accident. Eighteen
      years later the patient had major abdominal surgery performed for an unrelated
      condition and, at the time of surgery, over 100 splenic nodules were found
      embedded throughout the patient's omentum, small bowel, and mesentery. An
      extensive study of immunological functions was carried out during the following 2
      years. Through the course of this investigation, it was determined that the
      patient's peripheral blood smear lacked Howell-Jolly bodies and deformed or
      damaged erythrocytes, indicating that the splenotic tissue had the capacity to
      remove intranuclear inclusions from circulating red cells and to phagocytose old
      erythrocytes. The patient's levels of complement, serum immunoglobulins and the
      numbers of circulating T and B lymphocytes, helper T cells, and
      cytotoxic/suppressor T cells all were within the normal range. The response to
      Streptococcus pneumoniae polysaccharides was also normal, with increased levels
      of specific antibodies to all serotypes included in the vaccine 4 months after
      immunization. Finally, histological examination of his biopsied splenotic nodules
      revealed tissue that was indistinguishable from normal spleen.

PMID- 7828369
TI  - Repair of immunoglobulin response in B cell line (JK32.1) originating from
      immunodeficient patient via implantation of functional plasma membranes.
AB  - Human-human B cell hybridoma JK32.1, constructed from B lymphocytes of a common
      variable immunodeficient patient and nonsecreting cell line, retains the defects
      of B cell immunodeficiency. Efforts to clarify whether the defect is located
      within the plasma membranes of this cell line were carried out by implanting them
      with plasma membrane fraction derived from normal functional cells via intact non
      infectious Sendai virus. The implanted cells were activated with various mitogens
      and their Ig responses and isotype switching were examined. Restoration of IgM
      secretion was achieved in the implanted JK32.1 cells following stimulation with
      SAC, PWM, or retinoic acid. Augmented IgM response was also obtained in the
      implanted cells treated with retinoic acid and lipopolysaccharide (LPS) despite
      their unresponsiveness to LPS alone. No IgG or IgA response could be detected in
      the implanted JK32.1 cells. These data suggest that this immunodeficient cell
      line possesses at least two different malfunctions, one located within the plasma
      membrane moiety of the cells and the other located within the cytoplasmic and/or
      nucleic components. The plasma membrane moiety defect can be repaired temporarily
      by delivering proper signals via the implanted plasma membranes. However, this
      manipulation of the cells could not overcome the intrinsic defect of the cells
      which blocks isotype switching and secretion of IgG, IgE, and IgA antibodies.

PMID- 7828370
TI  - V gamma 9-V delta 2+ gamma delta T cells from a patient with Felty syndrome that
      exhibit aberrant response to triggering of the CD3 molecule can regulate
      immunoglobulin secretion by B cells.
AB  - Expanded populations of T lymphocytes bearing gamma delta T cell receptors have
      been detected in several patients with Felty syndrome. The goal of this study was
      to functionally characterize these lymphocytes in a newly described patient with
      this disease. For this, fluorescence-activated cell sorter analysis of T cell
      surface antigens, proliferation, and tumor necrosis factor alpha enzyme-linked
      immunosorbent assays, as well as quantitative assays of immunoglobulins secreted
      by pokeweed mitogen-driven B cells were performed. The gamma delta cells, that
      expressed a CD3+CD4-V gamma 9-V delta 2+C delta + phenotype, and constituted 60%
      of the peripheral blood T cells, did not proliferate after triggering with anti
      CD3, but did secrete tumor necrosis factor alpha and the addition of these cells
      to pokeweed mitogen-stimulated B cells from the patient decreased their secretion
      of immunoglobulin M while augmenting IgG secretion. These data suggest that the
      expanded anergic V gamma 9-V delta 2+ gamma delta cells can play an
      immunoregulatory role in the patient.

PMID- 7828371
TI  - Molecular mimicry as a possible cause of autoimmune reactions in celiac disease?
      Antibodies to gliadin cross-react with epitopes on enterocytes.
AB  - Structural similarities between external antigen and self components are believed
      to be one of the possible causes of autoimmunity. This study describes the
      presence of similar structures shared by gliadin and enterocyte surface molecules
      recognized by antigliadin mAbs. The reactivity of mAbs to gliadin was followed by
      ELISA using fixed enterocytes, their brush-border membranes, or purified
      enterocyte antigen. The specificity of reaction was confirmed by ELISA inhibition
      studies and by immunohistochemical staining of rat tissue sections using biotin
      avidin-peroxidase technique. Immunoprecipitation analysis of 125I-labeled
      intestinal epithelial cells using antigliadin mAb revealed the presence of two
      main cross-reactive molecules of 28 and 62 kDa. The 62-kDa and an associated 66
      kDa protein were isolated by affinity chromatography. Immunoblotting analysis
      showed that a 28-kDa protein detected by immunoprecipitation also reacted with
      IgA of celiac disease patient sera.

PMID- 7828372
TI  - The abnormal lpr double-negative T cell fails to proliferate in vivo.
AB  - Mice homozygous for the autosomal recessive gene lpr develop marked
      lymphadenopathy and a systemic autoimmune disease resembling human systemic lupus
      erythematosus. The enlarged nodes are dominated by T cells with an unusual
      surface phenotype: dull Thy-1+, dull CD3+, CD4-, CD8-, B220+ (double-negative T
      cells or DNTs). Despite their massive accumulation in vivo, these cells fail to
      proliferate in response to conventional T-cell mitogens in vitro. The
      identification of the lpr mutation as a defect in the Fas apoptosis receptor gene
      suggests that DNT accumulation may result from abnormal persistence rather than
      overproliferation. To test in vivo whether DNTs persist abnormally or have a
      capacity to differentiate into single-positive T cells, we have performed cell
      transfer experiments between congenic strains of lpr and +/+ mice differentially
      marked by expression of the Ly-1 or Thy-1 alleles. Although transferred lpr lymph
      node cells were mostly DNTs at the time of injection, most recovered cells of
      donor origin were single positive, particularly CD8+, at all time points after
      transfer. Furthermore, transfer of purified DNTs resulted in recovery of
      relatively few cells of donor origin. Transfer of lpr T cells enriched for CD8
      expression confirmed the preferential survival of this subset. Thus, DNTs are a
      surprisingly transient population and have little capacity for transformation to
      single positives. This would suggest that DNTs are constantly being renewed,
      perhaps from CD4+ and CD8+ precursors.

PMID- 7828373
TI  - Bispecific HER2 x CD3 antibodies enhance T-cell cytotoxicity in vitro and
      localize to HER2-overexpressing xenografts in nude mice.
AB  - Recently, we reported the development of fully humanized bispecific F(ab')2
      antibodies with dual binding specificities to human T-lymphocytes and to tumor
      cells overexpressing HER2. These antibodies were shown to effectively mediate
      targeted HER2-overexpressing tumor cell killing by freshly isolated human T
      cells. In this report we extend our studies to describe the interaction of the
      bispecific antibody with activated T-lymphocytes (ATL) maintained in culture for
      an extended period of time. A microtiter plate radioreceptor assay was used to
      elucidate the affinity of bispecific antibody binding to ATL. The data show that
      ATL maintained in vitro for up to 5 weeks continued to express high-affinity CD3
      surface markers that bound to bispecific antibody with a Kd of 2.49 nM and
      exerted cytolytic activities against targets overexpressing HER2. In addition, we
      demonstrated the specific localization of HER2 x CD3 bispecific antibody to HER2
      overexpressing tumor xenografts in nude mice. Furthermore, HER2 x CD3 bispecific
      antibody has the ability to inhibit the proliferative activities of breast tumor
      (SKBR-3) cells in vitro. The clinical implications of these data are discussed.

PMID- 7828374
TI  - Anti-microfilament IgG antibodies in normal adults and in patients with
      autoimmune diseases: immunofluorescence and immunoblotting analysis of 201
      subjects reveals polyreactivity with microfilament-associated proteins.
AB  - We have investigated IgG antibodies to microfilament-associated proteins in sera
      from 29 normal controls and from 172 patients with autoimmune diseases such as
      rheumatoid arthritis (n = 45), systemic lupus erythematosus (n = 43),
      polymyositis/dermatomyositis (n = 36), systemic sclerosis (n = 35), and
      autoimmune chronic active hepatitis (CAH, n = 13). We observed, by indirect
      immunofluorescence, a staining pattern in which the fluorescence was continuously
      distributed along microfilaments by using several animal and human cell lines as
      substrate. Because no reactivity with individual bands or specific combinations
      of bands was observed by immunoblotting using different cell lines, we further
      characterized our sera by immunoblotting using a panel of the purified
      microfilament-associated proteins filamin, myosin, alpha-actinin, actin,
      tropomyosin, and myosin light chain. Results shows that normal as well as
      autoimmune sera are polyreactive with microfilament proteins. The specificity of
      reactivity against a particular microfilament-associated protein was demonstrated
      by inhibition experiments with the specific protein. No correlation was observed
      between immunoblot and immunofluorescence results. Of the 201 sera, 40 (20%), 42
      (21%), 31 (15%), 26 (13%), 34 (17%), 24 (12%), 4 (2%), and 0 (0%) reacted,
      respectively, by immunoblotting with 0, 1, 2, 3, 4, 5, 6, or 7 of the
      microfilament-associated proteins. Furthermore, 57 different profiles of
      reactivity with the panel proteins were observed. All autoimmune CAH sera reacted
      with at least 3 proteins. This result was strikingly unique to this group. Anti
      actin antibodies were as common in normal as in CAH sera. Anti-alpha-actinin
      antibodies were strikingly more frequent in CAH than in any group. We conclude
      that a remarkable diversity of anti-microfilament antibodies is present in normal
      as well as in autoimmune sera and that a continuous microfilament fluorescent
      pattern is not restricted simply to anti-actin antibodies. Furthermore, sera
      negative by immunofluorescence react with several miocrofilament-associated
      proteins by immunoblotting. Reactivity with multiple (> or = 3) microfilament
      associated proteins including alpha-actinin distinguishes CAH sera from normal
      and other autoimmune sera.

PMID- 7828375
TI  - Differing frequency of autoantibodies to glutamic acid decarboxylase among
      Koreans, Thais, and Australians with diabetes mellitus.
AB  - The wide racial-geographic differences in the incidence and prevalence of insulin
      dependent diabetes mellitus (IDDM) between Europids and Asian populations
      prompted us to compare frequencies of positivity of autoantibody to glutamic acid
      decarboxylase (GAD). The patients with IDDM included 41 Koreans, 30 Thais, and 45
      Australian Europids; the Koreans included 14 cases regarded as atypical IDDM by
      reason of a delayed requirement for insulin treatment. Autoantibodies were
      measured by radioimmunoprecipitation using iodinated purified porcine brain GAD.
      The frequency of positive tests for anti-GAD of 30% (8/27) for Koreans and 51%
      (20/39) for Thais was significantly lower than the 84% (38/45) for Australian
      Europids, even after stratifying by age of onset. Correspondingly, the mean
      levels of anti-GAD among seropositive cases were significantly lower for Koreans
      than for Australian Europids. In contrast to Thais and Australians, more than
      half the Koreans were diagnosed at age > 20 years, but there was no significant
      difference in positivity for anti-GAD between those over or under the age of 20
      at diagnosis. The different frequency of positivity in tests for anti-GAD among
      Koreans, Thais, and Australian Europids with IDDM suggests that there is a
      greater etiologic heterogeneity of IDDM among Asian than Europid populations, in
      whom autoimmune destruction of pancreatic islets predominates.

PMID- 7828376
TI  - Progress in pharmacology.

PMID- 7828377
TI  - The erythromycin breath test predicts the clearance of midazolam.
AB  - Midazolam, a commonly used sedative and amnestic medication, has recently been
      shown to be largely metabolized in the liver by a cytochrome P450, termed CYP3A4.
      There is at least a tenfold intersubject variability in the liver content and
      catalytic activity of CYP3A4, which may in part account for the known
      interpatient differences in the kinetics of midazolam. To test this hypothesis,
      we determined the intravenous midazolam kinetics of 20 medically stable,
      hospitalized patients, whose hepatic CYP3A4 activities were determined with use
      of the [14C-N-methyl]erythromycin breath test. During the kinetic study, we also
      performed psychometric testing designed to quantitate the level of sedation and
      amnesia. We found a significant positive correlation between the erythromycin
      breath test results and weight adjusted clearance (in milliliters per minute per
      kilogram) of both total midazolam (r = 0.52; p = 0.03) and unbound midazolam (r =
      0.61; p < 0.01). The relatively low dose of midazolam used (0.0145 mg/kg)
      produced significant but transient sedation and memory impairment in some of the
      patients. We conclude that interpatient differences in liver CYP3A4 activity in
      part account for the variations in midazolam kinetics. Our observations account
      for reported drug interactions involving midazolam and suggest that patients with
      low CYP3A4 activity may be most susceptible to prolonged amnestic effects
      occasionally produced by this short-acting benzodiazepine.

PMID- 7828378
TI  - Low CYP1A2 activity in rural Shona children of Zimbabwe.
AB  - Caffeine is increasingly used as a biochemical probe for liver function, in
      cancer epidemiology, and in pharmacogenetics, with its recognized ability to
      assess the activities of CYP1A2, xanthine oxidase, and N-acetyltransferase-2. The
      activity of these hepatic enzymes was tested in 45 Shona children from a rural
      area of Zimbabwe with use of caffeine as a probe. Many of these rural black
      children had lower indexes of CYP1A2 activity than otherwise on our extensive
      records; the average value (3.78 +/- 2.9) was significantly (p < 0.001) lower
      than that of healthy white urban children from Zimbabwe (8.86 +/- 3.36) or from
      Canada (7.92 +/- 1.88), or that of healthy Canadian adults (5.96 +/- 2.4). A
      higher CYP1A2 activity in children than in adults is usual. The low CYP1A2
      activity of the children from rural Zimbabwe calls for medical studies and
      suggests a widespread and perhaps serious impairment of certain liver functions.
      Causes could be parasitic infections with Schistosoma mansoni, causing
      schistosomiasis, which are endemic, in addition to generally poor nutrition and
      frequent iodine deficiency. By contrast, the xanthine oxidase activity in rural
      Shona children was slightly higher than that reported for a healthy Canadian
      adult population. The N-acetyltransferase activities were comparable in both the
      rural and urban children and were also similar to those reported in a population
      study of healthy adult Canadians.

PMID- 7828379
TI  - Pharmacodynamics of daily subcutaneous recombinant human interleukin-3 in normal
      volunteers.
AB  - Normal volunteers received subcutaneous injections of recombinant human
      interleukin-3 (rhIL-3) on 4 consecutive days to characterize toxicity,
      pharmacokinetics, and hematopoietic effects. Dosages were 2.5, 5.0, and 7.5
      micrograms/kg/day (n = 6 subjects per group). Adverse effects consisted
      predominantly of flu-like symptoms such as fever and headache. Mean area under
      the serum concentration-time curve and maximum serum concentration were linearly
      related to dose. Serum clearance was not apparently related to dose. Clearance
      increased slightly but significantly between days 1 and 4. Rapid but modest
      elevations in neutrophil and eosinophil counts were observed during treatment.
      Mean platelet counts rose modestly, peaking on day 10. Increases of CD34+ cell
      counts were correlated with increases of colony-forming unit-granulocyte
      macrophage (peak, day 7).

PMID- 7828380
TI  - Pharmacokinetics and pharmacodynamics of the diuretic bumetanide in the elderly.
AB  - In a cross-sectional study of the pharmacokinetics and pharmacodynamics of
      peroral and intravenous bumetanide (0.5 mg, single dose), total and renal
      clearance of the diuretic was significantly lower in elderly persons than in
      young adults, resulting in higher bumetanide plasma levels in the aged. Nonrenal
      clearance, bioavailability, and the volume of distribution were not significantly
      changed. Together with the decreased delivery into the urine the diuretic and
      natriuretic effect of bumetanide was reduced in the elderly. Renal clearance of
      bumetanide was linearly related with creatinine clearance, hence the decreases in
      bumetanide clearance and diuretic efficacy in the elderly are attributed to the
      age-dependent decline in renal function. The bumetanide concentration in urine
      and the fractional sodium excretion were not different in the two age groups,
      suggesting that the decrease in diuretic response in the elderly is a result of a
      reduction in the number of functioning nephrons, whereas the response of the
      remaining nephrons to bumetanide is unaltered.

PMID- 7828381
TI  - Stereoselectivity in cardiovascular and biochemical action of calcium
      antagonists: studies with the enantiomers of the dihydropyridine nitrendipine.
AB  - OBJECTIVES: The cardiovascular and biochemical effects of R- and S-nitrendipine
      were studied in six healthy subjects in a single-blind placebo-controlled study.
      METHODS: After received oral doses of placebo, 20 mg R-, 80 mg R- (n = 5), 20 mg
      S-, and 20 mg racemic nitrendipine, heart rate, systolic, diastolic, and mean
      arterial blood pressure, leg blood flow, peripheral vascular resistance, plasma
      renin activity, norepinephrine, epinephrine, dopamine, and aldosterone plasma
      levels were measured before and up to 3 hours after administration. RESULTS:
      Neither placebo nor 20 or 80 mg R-nitrendipine caused significant changes of
      cardiovascular and biochemical parameters. After 20 mg S-nitrendipine and 20 mg
      racemic nitrendipine, significant changes in diastolic blood pressure (-9.1/-7.4
      mm Hg), heart rate (+21.9/+17.3 beats/min), leg blood flow (+6.8 ml.min-1.gm
      tissue-1), peripheral vascular resistance (-16.9 mm Hg.min.gm tissue.ml-1),
      norepinephrine (+476/+281 ng.L-1), and plasma renin activity (+9.5/+3.6 ng.ml
      1.hr-1) were observed. The changes in cardiovascular and biochemical parameters
      were closely related to the serum S-nitrendipine concentrations. CONCLUSIONS: It
      can be concluded that, after administration of the racemate, the S-enantiomer is
      responsible for the cardiovascular and biochemical effects observed and that S
      nitrendipine is at least an order of magnitude more potent than the R-enantiomer.

PMID- 7828382
TI  - Intention-to-treat analysis and the goals of clinical trials.

PMID- 7828383
TI  - Decreases in serum ubiquinone concentrations do not result in reduced levels in
      muscle tissue during short-term simvastatin treatment in humans.
AB  - Statins, which are commonly used drugs for hypercholesterolemia, inhibit 3
      hydroxy-3-methylglutaryl coenzyme A reductase, the rate-limiting enzyme in
      cholesterol synthesis. Important nonsterol compounds, such as ubiquinone, are
      also derived from the same synthetic pathway. Therefore it has been hypothesized
      that statin treatment causes ubiquinone deficiency in muscle cells, which could
      interfere with cellular respiration causing severe adverse effects. In this study
      we observed decreased serum levels but an enhancement in muscle tissue ubiquinone
      levels in patients with hypercholesterolemia after 4 weeks of simvastatin
      treatment. These results indicate that ubiquinone supply is not reduced during
      short-term statin treatment in the muscle tissue of subjects in whom myopathy did
      not develop.

PMID- 7828384
TI  - Celiprolol and propranolol for unstable angina pectoris.
AB  - BACKGROUND: Celiprolol, a novel beta-blocker, may be more effective than
      propranolol in unstable angina pectoris because of both its beta 1-receptor
      selectivity and its vasodilatory property. METHODS: Fifty-three patients with
      angiographic coronary artery disease but uncompromised left ventricular function
      and with recurrent angina pectoris in spite of bed rest, aspirin, and repeated
      sublingual administration of nitroglycerin were randomized for 1 week of
      treatment with equipotent doses of either the nonselective beta-blocker
      propranolol (80 mg/day) or celiprolol (200 mg/day). RESULTS: Angina frequency was
      higher in the propranolol group (p < 0.01), whereas myocardial oxygen demand as
      estimated by the double product (systolic blood pressure x heart rate) was
      equally reduced by the two beta-blockers. Forearm blood flow was higher in the
      celiprolol group (p < 0.001). A stepwise logistic regression analysis showed that
      the beneficial effects of the beta-blockers were largely dependent on their
      effect on peripheral flow, in addition to reduction of the double product.
      CONCLUSIONS: Both celiprolol and propranolol largely reduce angina pectoris
      frequency in unstable angina pectoris. Celiprolol contributes to nearly complete
      relief in three times as many patients as propranolol; after adjustment for
      double product, it did so in eight times as many patients. The similar effects of
      the two compounds on the double product, and the essentially different effects on
      peripheral flow, support the theory that celiprolol exerts its beneficial effect
      to a large extent through its vasodilatory property.

PMID- 7828385
TI  - Lifibrol: a novel lipid-lowering drug for the therapy of hypercholesterolemia.
      Lifibrol Study Group.
AB  - OBJECTIVE: To determine the effects of lifibrol on serum lipids in adult patients
      with primary hypercholesterolemia. METHODS: These were two double-blind,
      randomized placebo-controlled studies. Each patient in each study had an 8-week
      dietary lead-in period on the American Heart Association Step I diet before
      administration of lifibrol or placebo. The first study consisted of active dosing
      of 4 weeks, and the second study had 12 weeks of active dosing. The setting for
      the study involved outpatients in private or university hospitals in the United
      States. All patients had primary hypercholesterolemia with low-density
      lipoprotein (LDL) cholesterol levels of > 160 mg/dl after the dietary lead-in
      period. There were 155 patients in the 4-week study and 336 patients in the 12
      week study. In the first study, patients were randomly assigned to receive either
      150, 300, 450, 600, or 900 mg lifibrol as a single daily dose for 4 weeks. In the
      second study, patients were randomized to receive either 150, 300, or 600 mg
      lifibrol for 12 weeks. Efficacy was determined by serial measurements of serum
      lipids either on a weekly or biweekly basis during each study. RESULTS: Compared
      with baseline, lifibrol reduced LDL cholesterol (> 40%, p < 0.0001) and
      apolipoprotein B (approximately 40%, p < 0.0001) by 4 weeks in both studies.
      After 6 weeks, high-density lipoprotein (HDL) cholesterol levels increased in the
      placebo and 150 and 300 mg lifibrol groups. In the 600 mg lifibrol group,
      triglycerides (approximately 25%, p < 0.001), lipoprotein (a) (approximately 30%,
      p < 0.001), and HDL cholesterol (approximately 5%, p < 0.002) decreased. Lifibrol
      reduced key sterol intermediates (e.g., lanosterol, lathosterol, beta-sitosterol,
      and campesterol) and increased serum bile acids, but it had no effect on urinary
      mevalonic acid excretion. The pharmacokinetics of lifibrol are independent of
      dose and are similar in men and women. Lifibrol was well tolerated. The most
      frequent medical event in both studies was skin rash. CONCLUSIONS: Lifibrol is a
      potent lipid-lowering drug in patients with hypercholesterolemia.

PMID- 7828386
TI  - Possible inhibition of hepatic metabolism of quinidine by erythromycin.
AB  - OBJECTIVE: To present and analyze a patient case illustrating a possible drug
      interaction between quinidine and erythromycin. METHODS: This is a case report of
      one hospitalized patient. The setting for this analysis was a university
      hospital. Through a MEDLINE search of all English medical literature (1966 to
      1994) documenting possible interactions between quinidine and erythromycin,
      retrospective patient chart review, and analysis of the relationship between
      serum quinidine concentrations and significant clinical events, deduce the
      possibility of a quinidine and erythromycin pharmacokinetic and pharmacodynamic
      interaction in this particular patient case. RESULTS: This case demonstrated a
      probable erythromycin-quinidine pharmacokinetic interaction that led to a
      decrease in quinidine apparent clearance, an increase in quinidine serum
      concentrations, and a possible quinidine toxicity. CONCLUSION: Serum quinidine
      concentrations, electrocardiograms, and other factors that may predispose
      patients to torsades de pointes, such as hypokalemia and hypomagnesemia, should
      be monitored closely if quinidine is coadministered with erythromycin.

PMID- 7828387
TI  - Evidence that cotinine is psychoactive?

PMID- 7828388
TI  - USAN Council. List No. 368. New names. Insulin lispro.

PMID- 7828389
TI  - Colour flow imaging of the orbit--concept or diagnostic tool?

PMID- 7828390
TI  - Crookshank Lecture: medical attitudes and patients' perceptions.

PMID- 7828391
TI  - Pathological-radiological correlations in benign lesions excised during a breast
      screening programme.
AB  - Benign biopsies are an inevitable part of any screening programme. They add
      significantly to the psychological and financial 'cost' of screening and so
      should be kept to a minimum. To identify possible means of reducing these false
      positive results we have reviewed the mammographic features of 108 benign lesions
      removed during prevalent round screening and correlations were sought with the
      pathological findings. The commonest mammographic abnormalities leading to benign
      biopsy were non-comedo type suspicious calcification (29%), poorly defined mass
      (21%), architectural distortion (19%) and a well defined mass (18%). The
      histological correlates were: non-comedo type suspicious calcification
      (fibrocystic change 60%, sclerosing adenosis 35%, and radial scar/CSL 13%),
      poorly defined masses (fibrocystic change 37%, fibroadenomas 37%, and sclerosing
      adenosis 25%) and architectural distortion (radial scar/CSL 61% and fibrocystic
      change 26%). Methods of reducing screening provoked benign biopsies are
      discussed.

PMID- 7828392
TI  - Indium-111 labelled leucocyte uptake in aortitis.
AB  - Inflammatory conditions of the aorta may present with non-specific clinical
      features, including unexplained fever. Indium-111 labelled leucocyte imaging may
      be performed in such patients to look for the presence of occult sepsis or to
      assess the activity of a known vasculitis. Of approximately 1100 patients to
      undergo leucocyte scintigraphy for these indications over a 5 year period, three
      had focal leucocyte uptake in the aorta. The final diagnoses were: (1)
      periaortitis in Wegener's granulomatosis; (2) aortic dissection in giant cell
      arteritis; and (3) streptococcal aortitis with impending rupture. In all three
      cases the uptake was initially not thought to be in the aorta, but in bowel, a
      paravertebral abscess and in the lumbar spine respectively. Further imaging with
      CT and MRI led to the correct diagnoses. As the aorta is a rare site of focal
      leucocyte uptake, errors in image interpretation are likely. The rapid diagnosis
      of inflammatory conditions of the aorta is essential, however, as they may be
      life-threatening if unrecognized; therefore awareness of the aorta as a potential
      site of uptake is important. Urgent referral for further imaging is imperative in
      these cases as a false or delayed diagnosis may lead to avoidable morbidity and
      mortality.

PMID- 7828393
TI  - Ultrasound findings in renal parenchymal disease: comparison with histological
      appearances.
AB  - Ultrasound examination was carried out in 55 patients undergoing renal biopsy for
      suspected renal parenchymal disease. Analysis of sonographic and histological
      findings showed statistically significant positive correlations between renal
      size and the extent of glomerular hyper-cellularity and crescent formation and
      between cortical echogenicity and severity of glomerular sclerosis, crescent
      formation, interstitial inflammatory cell infiltration, tubular atrophy and
      interstitial fibrosis. Positive correlation was also observed between prominence
      of the medullary pyramids and glomerular sclerosis. The most marked sonographic
      abnormalities were seen in proliferative (including crescentic)
      glomerulonephritis, diabetic glomerulosclerosis and tubulo-interstitial
      nephritis. IgA, membranous and minimal change nephropathy were less likely to be
      associated with sonographic abnormalities. We conclude that certain sonographic
      appearances in renal parenchymal disease reflect the presence and severity of
      light microscopical abnormalities but, although ultrasound assessment provides a
      high positive predictive value for renal parenchymal disease, specific conditions
      cannot be distinguished.

PMID- 7828394
TI  - T1-weighted images with ECG gating using partial flip angle spin-echo imaging.
AB  - ECG-gated spin-echo imaging can reduce vascular artefacts compared with spin-echo
      scans without gating. However, this method produces poor T1-weighted images
      because the repetition time (TR) is limited by the heart rate. We investigated
      the value of low flip angle spin-echo imaging for increasing T1-dependent
      contrast when using ECG gating. Using computer simulation, the predicted contrast
      increased with decreasing the flip angle, and the effect was almost saturated at
      a flip angle of around 40 degrees. With the application of this flip angle, the
      identical image contrast as a T1-weighted image (TR = 400 ms) can be obtained
      within the heart rate range of 65 to 75 beats/min. For clinical evaluation, the
      tissue contrast index values ((signal intensity in the lesion-signal intensity in
      the muscle)2 x 100/signal intensity in the muscle) obtained by conventional spin
      echo and low flip angle spin-echo imaging were compared in 17 patients. The
      contrast index of low flip angle spin-echo images (74.0 +/- 52.0) was
      significantly higher than that of conventional spin-echo images (40.9 +/- 35.9).
      Thus, ECG-gated low flip angle spin-echo imaging provided better T1-dependent
      contrast than conventional ECG-gated spin-echo imaging. This method may be
      especially useful for Gd-DTPA-enhanced magnetic resonance imaging.

PMID- 7828395
TI  - Potassium supplements prevent serious hypokalaemia in colon cleansing.
AB  - The association between colonic cleansing and hypokalaemia was studied
      prospectively by monitoring the serum potassium levels in four groups of
      patients: groups 1 (55 patients), 2 (72 patients), and 3 (97 patients) received
      the same 2-day preparation of 15 g magnesium sulphate and 10 mg bisacodyl twice
      daily; group 4 (96 patients) received a 1-day preparation of 2.4 mg sennoside per
      kg of bodyweight. Groups 1 and 2 were on diuretics, but only group 2 received
      potassium supplementation. Serum potassium levels were measured before and after
      bowel preparation. Hypokalaemia was present prior to cleansing in six (11%), and
      after cleansing in 20 (36%) of the 55 patients in the group 1 patients on
      diuretics but without potassium supplements. There was, after cleansing, no
      significant fall in serum potassium in the group 2 patients on diuretics who
      received potassium supplements. No hyperkalaemia resulted from supplementation. A
      significant fall of the mean level of serum potassium occurred in patients in
      both group 3 (2-day-preparation) and group 4 (1-day-preparation). We conclude
      that both 1 day and 2 days of cleansing with cathartics may result in a
      significant fall in serum potassium, which can be prevented by oral potassium
      supplements. Potassium supplements (three times a day 15 ml of potassium chloride
      with 0.9 mmol K per ml during the preparation) in patients on diuretics may be
      prudent to avoid the risk of cardiac arrhythmia.

PMID- 7828396
TI  - CT evaluation of otorrhagia associated with condylar fractures.
AB  - To assess a simplified CT evaluation of otorrhagia due to condylar fracture, 16
      patients with post-traumatic otorrhagia underwent axial CT of the petrous bones
      and coronal CT of the temporo-mandibular joints (TMJs). Bilateral high condylar
      fractures were demonstrated in seven patients. Unilateral subcondylar fracture
      dislocations with contralateral high condylar fractures were demonstrated in the
      other nine patients. The otorrhagia was always ipsilateral to a high condylar
      fracture. Otorrhagia due to condylar fractures occurred when the fracture was
      bilateral and ipsilateral to a high condylar fracture. The diagnostic procedure
      of choice is coronal CT of the TMJs which should be carried out if axial CT of
      the petrous bones showed them to be intact.

PMID- 7828397
TI  - Intravenous contrast media reactions: how do radiologists react?
AB  - Following the publication of the Royal College of Radiologists guidelines for the
      management of reactions to intravenous contrast media we assessed radiologists'
      understanding of intravenous contrast media reactions and their management of
      specific adverse reactions. A confidential questionnaire was sent to all
      radiologists in the Northern Region. Responses were received from 61/101 (60%).
      Knowledge of minor contrast media reactions was generally good but the
      understanding of treatment of severe reactions was poor. Knowledge of optimal
      management was inversely related to radiological seniority. This study suggests a
      poor understanding of severe contrast media reaction management amongst
      radiologists. Simplified treatment guidelines based on the Royal College document
      and aimed at severe reactions are suggested.

PMID- 7828398
TI  - Multiple cavitating pulmonary lesions in non-Hodgkin's lymphoma.
AB  - We report two patients with multiple cavitating lung lesions caused by large cell
      non-Hodgkin's lymphoma. This pattern of disease has rarely been reported in non
      Hodgkin's lymphoma and is more commonly described in Hodgkin's disease. The
      patterns of pulmonary parenchymal involvement in non-Hodgkin's lymphoma are
      reviewed with particular reference to cavitary lesions.

PMID- 7828399
TI  - Intraluminal bile duct hepatocellular carcinoma.
AB  - Jaundice is usually a late feature in the course of hepatocellular carcinoma and
      is only rarely due to obstruction. We present two cases of obstructive jaundice,
      in which the cause of obstruction in both patients was a massive intraluminal
      filling defect within the common bile duct which proved to be hepatocellular
      carcinoma. The radiological features are described.

PMID- 7828400
TI  - Localized perforation into the transverse mesocolon demonstrated during barium
      enema--rare but benign.
AB  - We report two cases demonstrating the presence of gas in the transverse mesocolon
      following asymptomatic perforation, shown during barium enema examination. The
      appearances, diagnosis and successful conservative management are described.

PMID- 7828401
TI  - Technical report: Hickman catheter rescue.
AB  - Nineteen malfunctioning or incorrectly positioned Hickman catheters from a series
      of 320 catheter placements were referred to the radiology department for salvage.
      Successful catheter 'rescue' was achieved on 14 occasions (73.6%). Eight
      catheters were repositioned, five were replaced and thrombolysis was successful
      in a patient with subclavian vein thrombosis. Catheter repositioning techniques
      are reviewed and a new technique for catheter replacement using the existing
      venous access and subcutaneous tunnel is described.

PMID- 7828402
TI  - Case report: HIV-related rapidly progressive carcinoma of the cervix AIDS--CT and
      MRI findings.
AB  - The computed tomography (CT) and magnetic resonance imaging (MRI) findings of a
      case of a large rapidly progressive invasive carcinoma of the cervix in an HIV
      positive women are presented. It produced retroperitoneal and lymph node
      metastases that were large, necrotic and rapidly growing. These findings are now
      recognized as being diagnostic of AIDS.

PMID- 7828403
TI  - Case report: computed tomography appearances in a right paraduodenal hernia.
AB  - The computed tomography (CT) appearances of a right paraduodenal hernia are
      described. The working diagnosis at the time of the scan was of acute
      pancreatitis and we discuss the differentiation of the two conditions on CT. The
      CT findings are compared with those previously reported in other types of
      internal hernia.

PMID- 7828404
TI  - Case report: cellist's elbow?--vascular entrapment in association with the
      ligament of Struthers.
AB  - We present a case of forearm claudication due to ulnar artery entrapment by the
      ligament of Struthers. Anatomical, radiological and surgical features of this
      uncommon syndrome are discussed.

PMID- 7828405
TI  - Bowel preparation for barium enemas.

PMID- 7828406
TI  - BS5750.

PMID- 7828407
TI  - Enteroclysis--the influence of enteroclysis tube design.

PMID- 7828408
TI  - Can radiologists manage reactions to intravascular contrast media?

PMID- 7828409
TI  - Peripheral blood lymphocyte subsets in multiple myeloma and monoclonal gammopathy
      of undetermined significance.
AB  - Peripheral blood lymphocyte subsets were analysed by flow cytometry and compared
      among 43 patients with untreated multiple myeloma (MM), 16 patients with
      monoclonal gammopathy of undetermined significance (MGUS) and 26 controls. The
      age and sex distributions of the patients and controls were comparable, which is
      important, since in the controls there was a significant effect of age and/or sex
      on the number of CD3+, CD57+, CD8+57+, CD16+ and CD3-56+ lymphocyte subsets, and
      on the CD4+/CD8+ and CD4+Leu-8+/CD4+ ratios. In MM, the number of CD8+ and CD57+
      cells and the CD4+/CD8+ ratio were related to the clinical stage. The number of
      CD20+, CD3+, CD4+, CD16+ and CD3-56+ cells and the CD3+/CD20+ ratio were
      significantly different in MM patients compared to age- and sex-matched controls
      as was the number of CD3+ and CD4+ cells of MGUS patients compared to controls.
      Further, there were significant differences in the CD3+/CD20+ ratio between MM
      and MGUS patients and between stage I MM and MGUS. The role of peripheral blood
      lymphocyte subsets in differentiating monoclonal gammopathies merits further
      study.

PMID- 7828410
TI  - Discriminant analysis of macrocytic red cells.
AB  - Laboratory classification of red cell disorders uses the red cell indices (MCV,
      MCH, MCHC, RDW) and information gleaned from microscopic evaluation of a blood
      film. Additional red cell information is now available using the H series of
      automated blood cell analysers (Ames Technicon Division of Bayer Diagnostics).
      This study involved the development of a discriminant rule which would
      differentiate between three causes of macrocytosis (vitamin B12/folate
      deficiency, alcohol excess/liver disease and a reticulocytosis) using the
      information available on Research Screen 1 and Report Screen 3 of the H*1
      instrument (Report Screen 3 is a graphical display of the trimmed scattergram of
      red cell volume and red cell haemoglobin concentration and Research Screen 1
      displays the associated numerical data). Three methods of analysis were assessed
      to define a suitable discriminant rule. The percentages of patients correctly
      classified by the three methods were: 92.1%, 82.0% and 89.2% for Methods 1, 2 and
      3 respectively. Method 1 involved the application of quadratic discrimination to
      transformed variables and produced the best results. Although complex, it could
      easily be applied using the microprocessor capability of the average
      multiparameter haematology analyser.

PMID- 7828411
TI  - The effect of red cell shape on the measurement of red cell volume. A proposed
      method for the comparative assessment of this effect among various haematology
      analysers.
AB  - Shape changes of abnormally deformed red cells in aperture impedance haematology
      analysers are known to affect MCV, MCHC and haematocrit estimation. However,
      different counters vary in the manifestation of this effect. We performed a
      comparative study among five analysers. Three of them are based on impedance
      without hydrodynamic focusing (Coulter STKR, Cell-Dyn3000 Abbott and K-1000
      Sysmex). The other two use hydrodynamic focusing, either with impedance (NE-8000
      Sysmex) or two angle laser scatter (H*1 Bayer). A novel method of analysis was
      applied. Two hundred and three specimens with abnormal red cells and 50 normal
      specimens (according to ICSH criteria) were assayed. In all samples the PCV was
      estimated by the reference method without correction for trapped plasma. A true
      MCHC value was estimated from the mean haemoglobin value and the PCV. The shape
      effect was assessed by three linear regressions: 1) haematocrit deviations from
      PCV (corrected for any calibration bias) versus true MCHC; 2) analyser MCHC vs.
      true MCHC; 3) MCV vs. MCH. The regressions for the analysers with hydrodynamic
      focusing indicated no significant shape effect. Aperture impedance analysers
      without focusing varied in their behaviour. The Coulter STKR and the Cell-Dyn3000
      both showed strong correlation of haematocrit deviations with true MCHC, poor
      MCHC correlations and linear MCV-MCH regressions. The K-1000 showed minor
      indications of such an effect. We conclude that comparative studies are needed to
      quantitate red cell shape effect errors among various impedance analysers.

PMID- 7828412
TI  - Blood transfusion in pregnancies complicated by maternal sickle cell disease.
      Effects on blood rheology and uteroplacental Doppler velocimetry.
AB  - Doppler ultrasound gives a measure of downstream resistance to blood flow. In
      this study it has been used to assess the change in placental vascular resistance
      following blood transfusion in pregnancies complicated by sickle cell disease.
      Eight women with homozygous sickle cell disease were followed prospectively to
      assess the effect of transfusion on haemoglobin S percentage, blood and plasma
      viscosity and uteroplacental Doppler velocimetry. Measurements were made
      immediately pre and post-transfusion and after several weeks when the desired
      improvement in haemoglobin S had been achieved. Despite significant changes in
      haemoglobin S levels and consequent rheological change there was found to be no
      change in measurements of resistance in the uteroplacental circulation as
      assessed by Doppler ultrasound.

PMID- 7828413
TI  - Validation of a single point flow cytometric assay for determining P-glycoprotein
      activity in multidrug resistant cell lines.
AB  - P-glycoprotein, a transmembrane protein which acts as an energy dependent efflux
      pump, has been implicated as one mechanism of multidrug resistance (MDR) in human
      tumours. Commonly employed assays measure P-glycoprotein immunohistochemically or
      mdr1 messenger RNA. In this study we compared a single point flow cytometric
      assay for determining activity of P-glycoprotein with cellular expression of P
      glycoprotein determined by Western blot. Five cell lines, with varying levels of
      multiple drug resistance, were incubated with daunorubicin (DNR) in the presence
      (treated) and absence (control) of cyclosporine or verapamil, agents known to
      inhibit the activity of P-glycoprotein. The treated cell lines, along with non
      treated controls were examined for intracellular concentrations of DNR measured
      by fluorescence intensity using a flow cytometer. The ratio of fluorescence
      intensity expressed in the treated/control was used as an index of functional
      activity of P-glycoprotein. Functional activity of the P-glycoprotein as
      determined by flow cytometry correlates highly with cellular content of P
      glycoprotein measured by western blot (correlation coefficients of r = 0.90-0.98
      for the various cell line combinations). This method represents a rapid single
      point flow cytometric assay which may be suitable for screening clinical samples
      for P-glycoprotein activity.

PMID- 7828414
TI  - The effect of cytokines on the in-vitro erythropoietin bioassay.
AB  - The effects of various concentrations of granulocyte macrophage colony
      stimulating factor (GM-CSF), gamma interferon (gamma IFN) and interleukins 1
      alpha (IL-1 alpha), 1 beta (IL-1 beta) and 3 (IL-3) on the anaemic mouse spleen
      cell bioassay for erythropoietin (EPO) were investigated. Addition of IL-3 and GM
      CSF at various concentrations had no effect on EPO stimulated 3H thymidine
      incorporation. However the addition of IL-1 alpha, IL1-beta and gamma IFN (3.3 x
      10(-8) gl-1) caused a significant (P < 0.01) inhibition of EPO stimulated
      thymidine incorporation. This suggests that the EPO bioassay may be influenced by
      variable levels of some inflammatory cytokines in serum. Previous studies have
      shown that the bioassay is influenced by serum transferrin levels and thus serum
      immunoassays remain the technique of choice for specific estimates of EPO. Since
      EPO bioassays are not specific, they should be reserved for situations in which
      an estimate of the total erythropoietic activity of serum is required.

PMID- 7828415
TI  - New approaches to cross-matching.

PMID- 7828416
TI  - Therapy-related acute myeloid leukaemia following immunosuppression with
      azathioprine for polymyositis.
AB  - A 52-year-old man developed therapy-related acute myeloid leukemia (AML)
      following prolonged immunosuppression with azathioprine for polymyositis.
      Karyotypic analysis showed deletions of the short arm of chromosome 7 and the
      long arm of chromosome 5. The importance of recognizing this potential
      complication while treating benign rheumatological and immunological diseases
      with purine analogues like azathioprine is emphasized. Therapy-related AML is a
      poor prognostic group that does not respond favourably to standard induction
      therapy.

PMID- 7828417
TI  - Systemic mastocytosis--a case treated with interferon alpha and radiotherapy.
AB  - Systemic mastocytosis is uncommon. Symptoms result from local infiltration and
      degranulation of mast cells. Reports in the literature describe successful use of
      interferon alpha and radiotherapy to produce reduction in symptoms and bulk of
      disease. We report a patient who responded to radiotherapy but not interferon
      alpha.

PMID- 7828418
TI  - A case of immunodeficiency characterized by neutropenia, hypogammaglobulinaemia,
      recurrent infections and warts.

PMID- 7828419
TI  - Warfarin sandwiches.

PMID- 7828420
TI  - Elevation of serum haptoglobin and beta 2-microglobulin levels during chronic
      idiopathic thrombocytopenic purpura.

PMID- 7828421
TI  - Skin puncture blood counts.

PMID- 7828422
TI  - Memory errors from a change of standard: a lack of awareness or of understanding?
AB  - Memory errors occur when the context standard that is used when judging target
      behaviors is different from the category norm standard that is available later
      when the behaviors are recalled. Is insufficient awareness the reason for this
      change-of-standard effect? Two kinds of awareness were maximized in each of two
      studies: (a) awareness of the relation between the judgment and the context-
      telling subjects to be sure to use the non-target persons for comparison when
      judging the target person (salience); and (b) awareness at recall of the earlier
      judgmental context--asking subjects to recall the non-target persons before
      recalling the target person (reinstatement). Context reinstatement reduced memory
      errors. But when context reinstatement and salience were combined, the memory
      errors reappeared. In Study 2, an attempt at debiasing failed. The change-of
      standard effect is explained in terms of a "natural" tendency to use the current
      categorical meaning of a judgment to reconstruct the referent of its past
      contextualized meaning.

PMID- 7828423
TI  - Nouns and verbs in a self-styled gesture system: what's in a name?
AB  - A distinction between nouns and verbs is not only universal to all natural
      languages but it also appears to be central to the structure and function of
      language. The purpose of this study was to determine whether a deaf child who was
      not exposed to a usable model of a conventional language would nevertheless
      incorporate into his self-styled communication system this apparently essential
      distinction. We found that the child initially maintained a distinction between
      nouns and verbs by using one set of gestures as nouns and a separate set as
      verbs. At age 3:3, the child began to use some of his gestures in both
      grammatical roles; however, he distinguished the two uses by altering the form of
      the gesture (akin to morphological marking) and its position in a gesture
      sentence (akin to syntactic marking). Such systematic marking was not found in
      the spontaneous gestures produced by the child's hearing mother who used gesture
      as an adjunct to speech rather than as a primary communication system. A
      distinction between nouns and verbs thus appears to be sufficiently fundamental
      to human language that it can be reinvented by a child who does not have access
      to a culturally shared linguistic system.

PMID- 7828424
TI  - Domestic Animal Endocrinology Award.

PMID- 7828425
TI  - Increased free cortisol in plasma of dogs with portosystemic encephalopathy
      (PSE).
AB  - Dogs with portosystemic encephalopathy (PSE) are known to develop pituitary
      dependent hyperadrenocorticism, but there have been no reports on the plasma
      protein binding of cortisol in these dogs. Since the liver is involved in the
      synthesis of corticosteroid-binding globulin (CBG) and other transport proteins
      for cortisol, the binding characteristics of these proteins and thus the
      biologically-active free fraction of cortisol might be altered in dogs with PSE.
      We investigated the total concentration of cortisol and the free fraction and the
      free cortisol concentration in plasma of thirty-two dogs with PSE due to
      inherited portosystemic shunts or chronic active hepatitis with cirrhosis. We
      found a significantly higher free fraction (14.7 +/- 5.8%, P < 0.0001) and free
      cortisol concentration (26.3 +/- 23.1 nM, P < 0.001) in these dogs than in
      healthy controls (8.2 +/- 2.3% and 9.2 +/- 7.2 nM, respectively). Moreover, basal
      concentrations of total cortisol in the dogs with PSE were higher than in the
      healthy controls (190 +/- 146 nM v. 107 +/- 65, P < 0.01). The per cent free
      cortisol in plasma was not significantly correlated with the concentration of
      albumin or the total cortisol in plasma. We conclude that there is decreased
      binding of cortisol in plasma of dogs with PSE due to decreased hepatic synthesis
      of cortisol binding proteins. The presence of increased concentrations of free
      cortisol in these dogs indicates that their basal pituitary-adrenocortical
      activity was increased, probably due to aberrant neurotransmission in brain
      centers associated with pituitary function, as a result of hepatic
      encephalopathy.

PMID- 7828426
TI  - Posttranslational processing of progonadotropin-releasing hormone (proGnRH) in
      ewes.
AB  - Gonadotropin-releasing hormone (GnRH) is released from hypothalamic neurons into
      the hypophyseal-portal blood system following enzymatic cleavage of the
      decapeptide from a large precursor (proGnRH) molecule. The purpose of this study
      was to determine whether the ability of GnRH-producing neurons to synthesize
      and/or process proGnRH differed during physiological states associated with a
      suppressed and enhanced release of GnRH in ewes. Tissues were collected from
      ovariectomized ewes (OVX, n = 4), OVX-estradiol treated ewes (OVX-E, n = 5), and
      ewes (n = 7) slaughtered 5 d after parturition (PP). Following euthanasia and
      exsanguination, stalk-median eminence (SME), medial-basal hypothalamus (MBH) and
      preoptic areas (POA) were collected. Concentrations of GnRH and proGnRH were
      determined by radioimmunoassay using specific antisera. Concentrations of GnRH in
      the SME did not differ (P > .05) between OVX-E and OVX ewes, but both groups
      contained less (P < .05) GnRH than the SME from PP ewes (4.4 +/- 0.7, 12.1 +/-
      3.8 vs 24.3 +/- 5.1 fmol/mg tissue, respectively). Concentrations of proGnRH in
      SME mimicked those of GnRH and were less (P < .05) in OVX-E ewes than PP ewes,
      but were not different (P > .05) from those in OVX ewes (.34 +/- .34 vs 3.76 +/-
      1.53 and 1.7 +/- .78 fmol/mg, respectively). In the MBH, OVX-E ewes had greater
      (P < .05) concentrations of GnRH than PP ewes (0.76 +/- 0.29 vs 0.24 +/- 0.04
      fmol/mg) and OVX ewes were intermediate (0.41 +/- 0.13 fmol/mg).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7828427
TI  - Effects of pituitary adenylate cyclase-activating polypeptide (PACAP),
      prostaglandin E2 (PGE2) and growth hormone releasing factor (GRF) on the release
      of growth hormone from cultured bovine anterior pituitary cells in vitro.
AB  - The effect of pituitary adenylate cyclase-activating polypeptide (PACAP) on
      growth hormone (GH) release was compared with that of prostaglandin E2 (PGE2) and
      growth hormone releasing factor (GRF) from cultured bovine anterior pituitary
      cells in vitro. Both PACAP and PGE2 stimulated GH release at concentrations as
      low as 10(-9) and 10(-8) M, respectively, (P < 0.01). However, GRF released GH at
      a concentration as low as 10(-13) M (P < 0.01). Percent increases of GH compared
      with controls were not significantly different among GRF, PACAP, and PGE2 at 10(
      7) M; however, the increases of GH by the 10(-8) M GRF, PACAP and PGE2 were 196,
      118, and 27%, respectively, (P < 0.01), and 124, 65, and 1% in the 10(-9) M
      media, respectively, (P < 0.01). When GRF and somatostatin (SS) were added
      together, the GH releasing effect of GRF was blunted (P < 0.01). Similar
      bluntness were observed in PACAP and PGE2, when SS was added. The stimulatory
      effects of GRF and PGE2 together were similar to that by either GRF or PGE2
      alone. When GRF and PACAP were added together, the GH released by both
      secretagogues was greater than that by PACAP alone (P < 0.01); however, a
      synergistic effect was not clear when compared with GRF alone. These findings
      suggest that PACAP and PGE2 may modulate the release of GH in cattle.

PMID- 7828428
TI  - Insulin-like growth factor-II expression in developing skeletal muscle of double
      muscled and normal cattle.
AB  - Double muscled (DM) cattle possess nearly 40% more muscle fibers than normal
      muscled (NM) beef or dairy cattle. Previous work showed that serum from DM
      fetuses stimulated proliferation of L6 myoblasts to a greater extent than serum
      from NM fetuses. Although the exact role of insulin-like growth factor-II (IGF
      II) in the regulation of fetal myogenesis is unknown, it has been shown to serve
      as a autocrine-acting growth factor during terminal differentiation of myoblasts
      in mitogen-depleted culture media. Delay of IGF-II expression may alter the
      ultimate number of muscle fibers formed during fetal development. To investigate
      this, forty-seven skeletal muscle and twenty-nine liver samples were collected
      from NM fetuses representing fetuses grouped by crown-rump lengths (CRL) of < 20,
      21-30, 31-40, 41-50, 51-60, 61-70 or > 70 cm. Twelve DM fetuses representing 20,
      40, 50, and 85 cm were compared to NM groups with the same CRL. Total RNA
      preparations from these samples were subjected to northern and dot blot analysis
      using rat IGF-II and beta actin cDNAs and a human 28S rRNA oligomer. IGF-II
      transcripts of 4.5, 3.6, 2.75, 2.5, and 1.15 kilobases (kb) were detected in
      liver and muscle RNA from both DM and NM fetuses. Liver IGF-II expression
      increased (P < 0.05) in both DM and NM fetuses with CRL. Mean concentrations of
      muscle IGF-II mRNA initially increased (P < 0.05), then decreased (P < 0.05) with
      CRL in DM and NM fetuses. Muscle IGF-II mRNA was greater (P < 0.05) for NM
      fetuses compared to DM fetuses at 20 cm CRL, whereas at 53 cm CRL, DM muscle IGF
      II was greater (P < 0.05) than that of NM fetuses. These results show that the
      maximum expression of muscle IGF-II is delayed in DM fetuses compared to NM
      fetuses. This delayed expression may play an explicit role in controlling
      myogenesis in the development of double muscle cattle.

PMID- 7828429
TI  - Oxytocin synthesis and secretion from bovine corpora lutea exposed in vitro to
      cycloheximide and colchicine.
AB  - Two experiments were conducted to study the effects of cycloheximide and
      colchicine on prostaglandin F2 alpha (PGF2 alpha)-induced secretion and synthesis
      of oxytocin in bovine luteal tissue in vitro. Corpora lutea were collected from
      beef heifers on Day 8 of the estrous cycle. In Experiment 1, incorporation of
      [14C]-leucine into oxytocin synthesized and secreted by luteal slices after
      exposure to PGF2 alpha, cycloheximide and cycloheximide plus PGF2 alpha was
      examined. In Experiment 2, synthesis and secretion of oxytocin were evaluated in
      luteal slices incubated with colchicine and PGF2 alpha alone and in combination.
      Cycloheximide inhibited incorporation of labeled leucine into luteal proteins by
      more than 90% and no labeled oxytocin was detected in the media or tissue.
      Prostaglandin F2 alpha induced significant secretion of oxytocin that was not
      inhibited by cycloheximide. Tissue levels of oxytocin after incubation with
      cycloheximide and/or PGF2 alpha did not differ and were similar to those of the
      incubated control. Colchicine alone did not suppress oxytocin secretion and did
      not alter the ability of PGF2 alpha to induce significant secretion of this
      nonapeptide. Tissue concentrations of oxytocin after incubation with colchicine
      and/or PGF2 alpha did not differ. These studies indicate that secretion and
      replenishment of luteal oxytocin in vitro is not contingent upon de novo protein
      synthesis. Inability of colchicine to suppress oxytocin secretion and synthesis
      may have been due to the short duration of exposure of luteal tissue to the drug.

PMID- 7828430
TI  - Relationship between in vitro somatotroph function and growth in three-week-old
      barrows.
AB  - The relationship between in vitro somatotroph function and growth was examined in
      piglets demonstrating a continuous range of growth characteristics. Twenty
      barrows were sacrificed at 3 weeks of age for the collection of pituitary tissue
      and blood. Pituitary cells from each animal were cultured and exposed to vehicle
      (culture medium); .1, 1, and 10 nM growth hormone-releasing hormone (GHRH); 2 mM
      8-Br-cAMP (cAMP); 100 nM phorbol myristate acetate (PMA); and 59 mM KCl. All
      secretagogue treatments stimulated growth hormone (GH) secretion (p < .0001).
      Basal and stimulated GH secretion in culture, intracellular GH content (icGH),
      and serum insulin-like growth factor-1 (IGF-1) concentrations were all positively
      correlated with 3-week weight gain (p < .05). Concentrations of GH in the serum
      sample taken at sacrifice were not related to growth (p > .3). Intracellular GH
      content was correlated with in vitro GH secretion (p < .01) and serum IGF-1
      concentrations (p < .001). Somatotroph function was contrasted in the 7 largest
      and 7 smallest piglets (large, 8.3 +/- .3 kg, n = 7; small, 4.5 +/- .2 kg, n =
      7). Treatment with GHRH produced a dose-related increase in GH secretion in both
      experimental groups (p < .0001). No significant size x GHRH interaction was
      detected (p = .09), When contrasted with the small group, the large group
      demonstrated elevated GH secretion in culture (p < .01), icGH content (p < .001),
      and circulating IGF-1 (p < .001). The results of this study raise the possibility
      of a functional relationship between porcine somatotroph secretory activity and
      growth, mediated by IGF-1, which may be regulated by the quantity of GH available
      for release.

PMID- 7828431
TI  - Opioid modulation of gonadotropin releasing hormone release from the hypothalamic
      preoptic area in the pig.
AB  - Two experiments (Exp) were conducted to examine in vitro the release of
      gonadotropin releasing hormone (GnRH) from the hypothalamus after treatment with
      naloxone (NAL) or morphine (MOR). In Exp 1, hypothalamic-preoptic area (HYP-POA)
      collected from 3 market weight gilts at sacrifice and sagittally halved were
      perifused for 90 min prior to a 10 min pulse of morphine (MOR; 4.5 x 10(-6) M)
      followed by NAL (3.1 x 10(-5) M) during the last 5 min of MOR (MOR + NAL; n = 3).
      The other half of the explants (n = 3) were exposed to NAL for 5 min. Fragments
      were exposed to KCl (60 mM) at 175 min to assess residual GnRH releasability. In
      Exp 2, nine gilts were ovariectomized and received either oil vehicle im (V; n =
      3); 10 micrograms estradiol-17 beta/kg BW in 42 hr before sacrifice (E; n = 3);
      .85 mg progesterone/kg BW in twice daily for 6 d prior to sacrifice (P4; n = 3).
      Blood was collected to assess pituitary sensitivity to GnRH (.2 microgram/kg BW)
      on the day prior to sacrifice. On the day of sacrifice HYP-POA explants were
      collected and treated as described in Exp 1 except tissue received only NAL. In
      Exp 1, NAL increased (P < .05) GnRH release. This response to NAL was attenuated
      (P < .05) by coadministration of MOR. Cumulative GnRH release after NAL was
      greater (P < .05) than after MOR + NAL. All tissues responded similarly to KCl
      with an increase (P < .05) in GnRH release.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7828432
TI  - Circulation of estrogens introduced into the rectum or duodenum in pigs.
AB  - To determine the absorption and metabolism of 17 beta-estradiol (E2) by the
      rectum of the pig, 10 mg of crystalline E2 was placed in the rectum of
      prepubertal gilts in Experiment 1. Blood samples were subsequently obtained from
      hepatic portal and jugular veins and plasma was assayed for E2, estrone (E1), 17
      beta-estradiol-glucuronide (E2G), estrone-glucuronide (E1G) and estrone-sulfate
      (E1S). Concentrations of E2, E1, E2G, E1G, and E1S rose in the hepatic portal
      vein within 30 min and remained elevated for several hr. Concentrations of E2 in
      the hepatic portal vein represented 3% of the total estrogen detected in the
      hepatic portal vein during the 5 hr sampling period, indicating that most of the
      E2 was metabolized prior to entering the hepatic portal vein after absorption by
      the rectal mucosa. Concentrations of E2, E1, E2G, E1G, and E1S rose in the
      jugular vein and remained elevated for several hr. The rise in E2 and E1 in the
      jugular vein may have come from E2 and E1 in venous circulation from the rectum
      that entered the inferior vena cava bypassing the hepatic portal vein and liver.
      The net result of absorption of E2 from the rectum of gilts was a large rise in
      unconjugated and conjugated E2 and E1 in the peripheral circulation. In
      Experiment 2 prepubertal gilts fitted with jugular, hepatic portal, duodenal, and
      gall bladder catheters were infused into the duodenum with bile from pregnant
      gilts. Concentrations of E2, E1, E2G, and E1G were determined in gallbladder bile
      of gilts before infusion and at 470 min.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7828433
TI  - Effects of dietary rhIGF-I in neonatal calves on the appearance of glucose,
      insulin, D-xylose, globulins and gamma-glutamyl transferase in blood.
AB  - Cow colostrum is rich in insulin-like growth factors IGF-I and II, thus the
      dietary effects of recombinant human (rh) rhIGF-I on the newborn were of
      interest. The objective of this study was to examine the effect of dietary IGF-I
      upon selected blood components and gut absorptive development. Calves were
      blocked by birth weight and fed two times per d for a total of four times with
      the initial restricted diet. The initial feeding was 1.5 l and the remaining
      three feedings were at 2 l with one of three experimental diets; 1) milk replacer
      plus isolated colostrum derived globulins (MR-), 2) same as 1 above plus 750
      ng/ml rhIGF-I (MR+), 3) pooled cow colostrum (COL). Thereafter, all animals
      received only milk replacer at 5% of body weight (BW)/feeding two times per d
      with only treatment 2 having continued addition of 750 ng/ml rhIGF-I until
      experimental completion at 6 to 7 d after birth. At feeding three, animals were
      fed D-xylose (0.5 g/kg BW) and 5,000 U of bovine kidney membrane gamma-glutamyl
      transferase as indicators of gut absorptive capacity. Colostrum-fed animals
      received 5,000 U of natural occurring gamma-glutamyl transferase activity in the
      1.5 l first feeding. Blood samples taken over time were collected and saved as
      frozen plasma. All diets were analyzed for nutrient composition and endogenous
      levels of test hormones. Colostrum fed calves had greater globulin concentration
      (P < 0.01) than MR- or MR+ fed calves. Recombinant hIGF-I feeding had no effect
      (MR- vs. MR+) upon total protein, albumin or globulin blood levels. Absorption of
      colostrum gamma-glutamyl transferase at first feeding resulted in a peak total
      blood U of 4.5% of that fed. Although enzyme absorption was greatly reduced by
      the third feeding (0.5% of total fed), MR+ fed calves exhibited no significant
      difference in enzyme absorption when compared with the controls (MR- vs. MR+).
      However, pharmacokinetic analysis of D-xylose absorption at the third feeding
      showed diet effect upon absorption of D-xylose. Dietary rhIGF-I may change
      development or activity of sugar transporters and also may alter absorption of
      macromolecules (closure) in neonatal calves.

PMID- 7828434
TI  - Regulation of proteolytic activity in tissues.
AB  - Degradation of tissue proteins is controlled by multiple means. These include
      regulation of the synthesis of proteinases, activation of the zymogen forms, the
      activity of the mature proteinase, and the degradation of these enzymes and the
      substrates. Mature proteinases can be controlled by pH, calcium ions, ATP, lipids
      and the formation of complexes with other proteinases, proteoglycans, and
      inhibitors.

PMID- 7828435
TI  - Homeobox gene expression during development of the vertebrate brain.

PMID- 7828436
TI  - Evolution of developmental mechanisms: spatial and temporal modes of rostrocaudal
      patterning.

PMID- 7828437
TI  - Axonal guidance from retina to tectum in embryonic Xenopus.

PMID- 7828438
TI  - The in vivo roles of mullerian-inhibiting substance.
AB  - The fetal testis functions as the sex differentiator by imposing a masculine
      pattern of development upon a genetic program that is inherently female. Two
      hormones produced by the fetal testis mediate the differentiation of the
      mullerian and Wolffian ducts (Figs. 1 and 4). MIS actively inhibits the
      development of the mullerian ducts, and testosterone induces the differentiation
      of the Wolffian ducts. The absence of these two hormones during fetal development
      in the female (the hormonal equivalent of no testes) permits mullerian duct
      differentiation and does not induce Wolffian duct development. The in vivo
      outcomes of ectopic MIS exposure or MIS deficiency illustrate the balance
      required to coordinately differentiate and cause regression of the respective
      male and female genital ducts. The observations made in the MIS-deficient mice
      demonstrate that codevelopment of both genital duct systems interferes with
      normal development of both systems and ultimately interferes with reproduction
      and fertility. Thus, reproduction and fertility in mammals appear to be most
      efficient if only one type of genital duct system develops. The phenotypes of the
      MIS-overexpressing transgenic mice and the MIS-deficient mice are similar yet
      different. Some of the explanations that might reconcile these differences
      probably lie with the receptor for MIS. Since the MIS-overexpressing transgenic
      mice are exposed to pharmacological levels of MIS during development, it seems
      possible that this may lead to productive interactions with other related
      receptors. Candidate genes have been isolated for the MIS receptor that are
      membrane-bound serine/threonine kinases (Baarends et al., 1994; di Clemente et
      al., 1994) similar to those cloned for the TGF-beta (Lin et al., 1992) and
      activin (Mathews and Vale, 1991) type II receptors. Interestingly, expression of
      these putative MIS receptor genes is localized by in situ hybridization to the
      mesenchymal cells adjacent to the mullerian ducts, suggesting that MIS most
      likely alters the surrounding mesenchyme to elicit mullerian duct regression.
      Experiments are underway to isolate the mouse MIS receptor gene to thereby
      generate MIS receptor-deficient mice and to compare the phenotype with the MIS
      gain-of-function and loss-of-function animals. Isolation of the human MIS
      receptor gene will facilitate the identification of human PMDS patients with
      normal levels of MIS that have mutations in the MIS receptor gene. Finally,
      studies of the MIS receptor gene will open up avenues for the molecular
      characterization of signal transduction pathways that mediate mullerian duct
      regression and Leydig cell proliferation control.

PMID- 7828439
TI  - Mechanisms of genomic imprinting in mammals.
AB  - This chapter can be summarized by the following main points: Genomic imprinting
      results in the functional nonequivalence of the maternal and paternal genomes,
      thereby preventing the development of viable parthenogenotes and androgenotes in
      eutherian mammals. Imprinting may have arisen as a result of the specialized
      evolutionary requirements of the parental genomes or may have been an obligatory
      step in the development of placentation. A substantial proportion of transgenes
      and a smaller number of endogenous genes demonstrate imprinted pattern of
      expression in mice and humans. An analysis of DNA methylation in somatic tissues
      and germ cells during embryonic and postnatal development reveals dynamic
      changes, particularly during gametogenesis and early embryogenesis. The nature
      and timing of these changes suggest that DNA methylation may be involved in
      genomic imprinting. Imprinted genes display complex methylation patterns. Many
      aspects of these patterns are consistent with a role for methylation in the
      imprinted phenotype, although it is currently unclear whether methylation
      functions in the establishment of imprinting or plays a secondary role in the
      maintenance of the imprinted pattern of expression. Studies underway to identify
      new imprinted genes may help elucidate both the function and mechanism of genomic
      imprinting.

PMID- 7828440
TI  - Mechanisms of nondisjunction in mammalian meiosis.

PMID- 7828441
TI  - Timing of events during flower organogenesis: Arabidopsis as a model system.

PMID- 7828442
TI  - Homeobox and pax genes in zebrafish development.

PMID- 7828443
TI  - Mechanisms of increased sensitivity to A2 adenosine receptor stimulation in
      immature rabbit aortic rings.
AB  - Adenosine receptor-mediated vasodilation is increased in immature vessels
      compared to mature vessels. To determine the mechanism of this increased
      sensitivity, isolated vascular rings from mature and immature rabbits were
      studied to evaluate the contribution of the endothelium and the contribution of
      adenosine-dependent 3',5'-cyclic monophosphate (cAMP) to adenosine receptor
      mediated relaxation. Dose responses were measured in endothelial-intact and
      nonendothelialized aortic rings using 5'-(N-ethylcarboxamido)-adenosine (NECA), a
      nonhydrolyzable adenosine agonist. Immature rings were more sensitive to NECA
      than mature rings as demonstrated by a lower ED50 and steeper slope of the dose
      response curve. There was no effect on endothelial removal in immature rings
      while there was a significant decrease in response in mature rings. Despite being
      more sensitive to NECA, immature rings had less increase in cAMP (percent change
      from basal level) at maximal vasodilation than mature rings although cAMP did not
      change in either age at the ED50. The lack of change with endothelial removal in
      immature vessels suggests that the endothelium is not involved in the increased
      sensitivity of immature rings to NECA. The cAMP data suggests that other
      mechanisms for vasodilation are important at the ED50 for NECA in both ages.
      Maximal vasodilation with NECA on the other hand was associated with increases in
      cAMP although they were lower in the immature rings.

PMID- 7828444
TI  - Pharmacokinetics of paracetamol in the neonate and infant after administration of
      propacetamol chlorhydrate.
AB  - The pharmacokinetic parameters of paracetamol were studied after 15 min
      intravenous infusion of 15 mg/kg of propacetamol (Prodafalgan) in 5 neonates aged
      less than 10 days and 7 infants aged between 1 and 12 months. Blood was sampled
      at 0, 0.5, 2 and 6 h after the first intravenous infusion of propacetamol. The
      infants aged less than 10 days had higher plasma concentrations of paracetamol, a
      longer half-life (3.5 vs. 2.1 h) and a lower plasma clearance (0.149 vs. 0.365
      l/h/kg) than the older children. Dose simulations were performed on the basis of
      individual data of each child in order to obtain steady-state plasma
      concentrations between 4 and 18 mg/l permitting the best antipyretic effect for
      each child. In infants aged less than 10 days a 15 mg/kg dose of propacetamol
      four times a day (i.e. 30 mg/kg/day paracetamol) is sufficient, corresponding to
      the dosage recommended by the French pharmacopoeia. On the other hand, double the
      dosage, nearer to the American dosage, is necessary for children aged over 10
      days.

PMID- 7828445
TI  - Population pharmacokinetics of ceftizoxime in premature newborns.
AB  - The population pharmacokinetic parameters of ceftizoxime were determined in 50
      premature newborns less than 1 week of age (birth weight = 1.8 +/- 0.6 kg) with a
      clinical diagnosis of suspected sepsis. Each infant received ceftizoxime 25 mg/kg
      every 12 h intravenously over 30 min for a total of 6 doses. Serum concentrations
      of ceftizoxime were assayed by HPLC at 0.5, 1, 2.5 and 11.5 h or at 0.5, 1.5, 4.5
      and 11.5 h after the first and the sixth dose. A total of 184 serum
      concentrations following the first dose and 160 following the sixth dose were fit
      separately and then collectively to a one-compartment model using NONMEM. The
      separately estimated parameters were not significantly different between the
      first and the sixth dose. The final parameter estimates were 27.1 ml/h/kg, 333
      ml/kg and 8.5 h for clearance, volume of distribution and half-life,
      respectively. Other factors including gestational and postnatal age were not
      associated with alterations in ceftizoxime clearance. That the large variability
      in clearance was decreased from a coefficient of variation of 80 to 50% warrants
      dosing premature infants on the basis of body weight. The results of this study
      suggest that 25 mg/kg ceftizoxime every 12 h appears to be an appropriate dosing
      regimen for premature neonates.

PMID- 7828446
TI  - Supplementation and plasma levels of vitamin A in premature newborns at risk for
      chronic lung disease. Italian Collaborative Group on Preterm Delivery (ICGPD).
AB  - Deficiency of vitamin A (retinol) has been suggested as an important contributing
      cause in the pathogenesis of bronchopulmonary dysplasia (BPD) in premature
      newborns with severe lung disease. Although the efficacy of vitamin A
      supplementation has yet to be clearly confirmed, it is widely employed, at
      different dosages and schedules, in neonatal intensive care units (NICU). Since
      in Italy today no suitable formulation of vitamin A is available, the present
      observational study was designed to define the profile of plasma vitamin A and
      retinol-binding protein (RBP) concentrations in supplemented infants at risk for
      BPD admitted to seven Italian NICU. Twelve babies (average 27 weeks of gestation,
      birth weight 1,008 g), supplemented with vitamin A, were observed with sequential
      measurements of retinol and RBP up to 28 days of age. At birth retinol and RBP
      plasma concentrations were both adequate in the infants and half their mothers'
      levels. During supplementation the levels rose with wide variability according to
      the differences in dosing and timing in the different units. Plasma levels of
      retinol and RBP were the same in infants who had BPD and those who did not. A
      routine standardized therapeutic approach using vitamin A supplementation in
      Italian NICU will be more than welcome.

PMID- 7828447
TI  - Relative contribution of endothelium-derived relaxation factor to vascular tone
      in the systemic, pulmonary, and cerebral circulations of piglets.
AB  - We determined the contribution of endothelium-derived relaxation factor (EDRF) to
      vascular tone in the systemic, pulmonary, and cerebral circulations of piglets.
      METHODS: 11 piglets were anesthetized and mechanically ventilated. Systemic
      cardiac output was determined by an electromagnetic flow probe placed on the main
      pulmonary artery. Cerebral blood flow was assessed by determining unilateral
      internal carotid artery blood flow (ICBF) using a flow probe placed on the common
      carotid artery after ligation of the ipsilateral external carotid circulation.
      Progressive inhibition of EDRF was achieved by continuous infusion of the
      substituted L-arginine analog N-nitro-L-arginine (NNLA). Hemodynamic observations
      were compared at 0, 0.1, 1.0, 10, 30, and 80 mg/kg cumulative dose of NNLA.
      RESULTS: At all NNLA doses > or = 1 mg/kg, both systemic blood pressure and
      systemic vascular resistance were elevated. At all NNLA doses > or = 10 mg/kg,
      systemic cardiac output was reduced. At all NNLA doses > or = 10 mg/kg, pulmonary
      artery pressure and pulmonary vascular resistance were elevated. Although
      cerebral vascular resistance was elevated at all NNLA doses > or = 10 mg/kg, ICBF
      was maintained at or near baseline values up to a dose of 80 mg/kg. At all levels
      of EDRF inhibition, both the pulmonary and systemic circulations demonstrated
      approximately equal magnitudes of vasoconstriction. In contrast, at 30 and 80
      mg/kg cumulative dose of NNLA, the cerebral circulation was relatively less
      constricted by NNLA than was the systemic circulation. Systemic VO2 was
      significantly reduced at 30 mg/kg and 80 mg/kg cumulative NNLA dose, while
      cerebral VO2 was preserved at both NNLA doses. CONCLUSIONS: EDRF contributes to
      resting vasodilator tone in the systemic, pulmonary, and cerebral circulations in
      piglets. Progressive inhibition of EDRF constricts the systemic and pulmonary
      circulation equally. Inhibition of EDRF does not impair the ability of the brain
      to vary cerebral vascular resistance in order to redistribute blood flow towards
      itself during a period of reduced cardiac output.

PMID- 7828448
TI  - Comparison of acceptance of clinical versus basic studies on drugs and
      therapeutics in infants and children.
AB  - Many clinicians and clinician-scientists have serious concerns that clinical
      studies (i.e. studies with patients) are less favorably accepted than basic
      ('bench') projects by funding agencies and by promotion committees of university
      departments. However, this commonly held view has not been previously verified.
      To test whether bias exists against clinical studies, we compared the acceptance
      rate of clinical vs. basic studies dealing with drugs and therapeutics in
      children, which were submitted to a large scientific meeting. Of 197 abstracts
      reporting on drug/therapeutic studies, submitted to the Society for Pediatric
      Research in 1993, there were 133 clinical and 64 basic studies. Fifty-nine
      (44.3%) of the clinical studies were accepted, significantly less than the basic
      projects (n = 47 or 73.4%, p < 0.0001). A basic paper was 66% more likely to be
      accepted (95% CI 50.7-82.6%). This trend was consistent for different groups of
      drugs/therapeutics, including analgesics, surfactants, corticosteroids, vaccines,
      hormones, and antiasthmatics. To examine whether the lower rate of acceptance of
      clinical papers is the result of lower scientific standard, all papers were
      scored for their quality by raters who were blinded to their acceptance or
      rejection status. In general, rejected clinical papers scored significantly
      higher than rejected basic papers (16 +/- 1.8 vs. 14.8 +/- 1.0, p < 0.05). Our
      study supports the commonly held but previously unproven view that there is a
      bias against clinical research, in the context of patient-based studies, when
      compared to basic (bench) research.

PMID- 7828449
TI  - Pharmacokinetics of amikacin in neonates.
AB  - Only a few data have thus far been published on the pharmacokinetics of amikacin
      in neonates. To gain further information on this issue, we studied a series of 32
      neonates who were treated with amikacin for suspected or documented bacterial
      infection. Nineteen neonates were preterm (mean gestational age = 32.0 +/- 3.6
      weeks, mean body weight = 1.74 +/- 0.81 kg) while the remaining 13 were full-term
      (mean body weight = 3.19 +/- 0.82 kg). The 32 neonates were given amikacin by
      intramuscular route. A total of 121 concentrations were measured (average number
      of concentrations per patient = 3.8; range 3-6). To estimate amikacin
      pharmacokinetic parameters, the serum concentration values of the drug were
      fitted to the one-compartment pharmacokinetic model. The calculated
      pharmacokinetic parameters were the following (mean +/- SD): clearance = 64.6 +/-
      30.8 ml/h/kg; volume of distribution = 0.655 +/- 0.414 liters/kg; half-life = 7.6
      +/- 4.4 h. These results are similar to the values reported previously, with the
      important exception of the volume of distribution, which was considerably higher
      in our study. The intraindividual variability of amikacin pharmacokinetics was
      evaluated by the standard two-stage method yielding an intraindividual
      variability coefficient of 28.9%. No previous estimate of this parameter has as
      yet been published. The population parameters of amikacin in neonates, derived
      from the present study (i.e. coefficient for intraindividual variability and
      means +/- SD for clearance and volume of distribution), can be applied to a
      further series of neonates to facilitate the prospective use of the bayesian
      method for individualizing amikacin dosage.

PMID- 7828450
TI  - Overestimation of serum vancomycin concentrations using a fluorescence
      polarization immunoassay (Tdx) in preterm neonates.
AB  - Serum vancomycin concentrations determined by fluorescence polarization
      immunoassay (FPIA) with a specific high-performance liquid chromatography (HPLC)
      method in preterm neonates were compared. Preterm neonates (< 38 weeks
      gestational age) requiring vancomycin therapy and serum vancomycin concentration
      monitoring were enrolled. Peak serum vancomycin concentration samples were
      collected and independently analyzed by FPIA and HPLC. Multivariate and
      stratified data analysis was done with mean absolute error and mean percent error
      as dependent variables and independent variables as postconceptional age,
      postnatal age, gestational age, weight, and duration of therapy to characterize
      the findings. A total of 15 paired vancomycin concentrations were analyzed from
      neonates with a mean gestational age of 30 +/- 4 weeks. The mean percentage error
      of FPIA versus HPLC vancomycin concentrations was 18.1 +/- 11.1% and the mean
      absolute error was 3.7 +/- 2.0 mg/l. Postconceptional age, weight, and time from
      initiation of therapy to sample collection were independent variables which best
      characterized the overestimation of FPIA vancomycin concentrations. The FPIA
      vancomycin assay method overestimated actual vancomycin concentrations in preterm
      neonates. Preterm neonates less than 30 weeks postconceptional age, less than
      1,200 g body weight, and duration of therapy greater than 48 h prior to
      concentration determination had the greatest difference in FPIA and HPLC results.
      Significant error in pharmacokinetic parameter estimations and dosage adjustments
      is possible when vancomycin concentrations are determined by FPIA.

PMID- 7828451
TI  - Pharmacokinetics of cyclosporin A in 16 newborn infants of renal or cardiac
      transplant mothers.
AB  - Fourteen renal transplant and one heart transplant mothers receiving cyclosporin
      (mean dosage: 273 +/- 19 mg/day) underwent a Caesarean section at a mean
      gestational age of 34.1 +/- 1.9 weeks. Circulating cyclosporin was assayed by
      HPLC. The mean blood levels in the mothers before the Caesarean section were 210
      +/- 16 ng/ml, in cord blood 62 +/- 16 ng/ml (14 infants) and in the peripheral
      blood within 6 h of birth 31 +/- 12 ng/ml (15 infants); there was no correlation
      between maternal and cord levels, nor between peripheral blood levels at 2 h and
      cord blood levels. Cyclosporin levels were undetectable at day 3 in 12 infants,
      but low levels were found in 1 infant up to day 12. There was no toxic effect on
      the fetus or neonate.

PMID- 7828452
TI  - Induction of hepatic bilirubin and drug metabolizing enzymes by individual herbs
      present in the traditional Chinese medicine, yin zhi huang.
AB  - Yin Zhi Huang (YZH) is a decoction of four plants which is widely used in Asia to
      treat neonatal jaundice. This study compares the ability of phenobarbital and the
      individual herbs comprising YZH, Artemisia, Gardenia, Rheum, and Scutellaria
      baicalensis, to induce hepatic drug and bilirubin metabolizing enzymes in rats.
      Herbal decoctions (30 ml/kg/day) or phenobarbital (60 mg/kg/day) were
      administered for 5 days. Only phenobarbital increased cytochrome P-450 levels
      whereas Gardenia slightly decreased levels. Artemisia, Rheum and phenobarbital
      increased bilirubin glucuronyl transferase activity. Glucuronidation of alpha
      naphthol was increased by Gardenia and phenobarbital, whereas Artemisia and Rheum
      were ineffective inducers. Phenobarbital was the most effective inducer of
      glutathione-S-transferase (GSHT) activity. Phenobarbital and Gardenia both
      induced delta 5-3-ketosteroid isomerase activity, a marker for the Ya subunit of
      GSHT responsible for intracellular bilirubin transport in liver. The selective
      patterns of enzyme induction suggest potential value for using specific plant
      decoctions to modify drug and bilirubin metabolic pathways.

PMID- 7828453
TI  - Endothelin 1-21 plasma levels on the first and fourth postpartum day in normal
      full-term neonates.
AB  - Endothelins (ETs), recently discovered and highly vasoactive substances, have
      been implicated in the pathogenesis of various perinatal problems, such as
      preeclampsia, intrauterine growth retardation, intraventricular hemorrhage,
      pulmonary hypertension and necrotizing enterocolitis. Although fetal ET levels
      have been measured at birth, reference ET values for healthy newborns in the
      first days of life have not been established. The purpose of this study was to
      determine in normal healthy neonates ET 1-21 plasma values on day 1 and 4
      postpartum and to investigate possible changes after adaptation of the newborn to
      extrauterine life. The study comprised 20 healthy full-term neonates, born after
      vaginal delivery (n = 10), or cesarean section (CS; n = 10) because of a previous
      CS. Venous blood was drawn on day 1 and 4 from all neonates and ET 1-21 levels
      were determined in the plasma by radioimmunoassay (Amersham kit RPA 5559). ET 1
      21 values were on day 1 11.83 +/- 2.39 pmol/l (n = 20) and on day 4 9.45 +/- 1.88
      pmol/l (n = 20). The statistical analysis showed a significant reduction of
      plasma ET levels on day 4 (p = 0.004), but no influence of the mode of delivery
      on plasma ET levels. In conclusion irrespective of the mode of delivery the high
      ET 1-21 plasma levels on day 1 postpartum are significantly reduced on day 4 of
      life.

PMID- 7828454
TI  - Clinical and biochemical correlates of growth associated with short-term
      administration of methionyl growth hormone.
AB  - Twenty newly diagnosed growth hormone-deficient children (19 males) were
      randomized to receive methionyl growth hormone (0.3 mg/kg/week) in subcutaneous
      doses divided daily (n = 12) or 3 times per week (TIW). With the initial dose and
      at 4-6 weeks after beginning therapy, procollagen type III propeptide (PIIIP)
      concentrations were determined. Growth velocities were calculated before and at
      1, 3, and 6 months after beginning the therapy. Pretreatment growth velocities
      were 3.66 +/- (SD) 1.45 and 3.79 +/- 0.55 cm/year for the daily and TIW groups,
      respectively. At 1, 3, and 6 months mean growth velocities increased to 17.2,
      10.2, and 9.5 cm/year for the daily group and 9.8, 6.8, and 7.6 cm/year for the
      TIW group, with differences between groups significant (p < 0.05) at 1 and 3
      months. PIIIP concentrations increased significantly (p < 0.05) over 1 month in
      both groups, from 11.3 to 18.8 ng/ml and from 10.0 to 12.0 ng/ml in the daily and
      TIW groups, respectively. In addition PIIIP concentrations were significantly
      higher (p < 0.05) in the daily group at 1 month. A significant correlation was
      found between PIIIP concentrations at 1 month and the growth velocity at 1 (r =
      0.47), 3 (r = 0.60), and 6 (r = 0.67) months. Pretreatment growth velocity was
      weakly correlated with posttreatment growth velocity at both 1 (r = -0.45) and 3
      (r = -0.42) months. We conclude that (1) growth hormone is more effective when
      administered daily, (2) pretreatment growth velocity and PIIIP plasma
      concentration at 1 month correlate with 1 month growth velocity, and (3) PIIIP at
      1 month provides a good evaluation of 6 months' response to methionyl growth
      hormone therapy.

PMID- 7828455
TI  - Pharmacokinetics of dexamethasone following single-dose intravenous
      administration to extremely low birth weight infants.
AB  - The single-dose pharmacokinetics of dexamethasone were studied in 7 extremely low
      birth weight infants of mean (+/- SD) gestational age 25.6 +/- 0.5 weeks
      suffering bronchopulmonary dysplasia. A mean peak dexamethasone concentration of
      250.5 +/- 70.7 ng/ml was obtained following an intravenous bolus dose (0.369 +/-
      0.04 mg/kg dexamethasone) of dexamethasone sodium phosphate. Dexamethasone was
      measured in plasma by HPLC. Mean clearance (0.143 +/- 0.028 litres/kg/h) was
      approximately half that reported previously in children and adults, while the
      half-life (9.26 +/- 3.34 h) was 2- to 3-fold longer than in these patients. The
      volume of distribution (1.9 +/- 0.483 litres/kg) was larger than reported in a
      previous study in adults, but was similar to that determined in pediatric and
      adult patients in another study.

PMID- 7828456
TI  - Prediction of gentamicin concentrations in neonates and infants using a Bayesian
      pharmacokinetic model.
AB  - This study retrospectively characterized population-based pharmacokinetic
      parameters for gentamicin in neonates and young infants, and evaluated the
      predictive performance of these parameters in a Bayesian forecasting program.
      Population parameter estimates were determined from the serum concentration-time
      data of 19 neonates and infants using a one-compartment open infusion model and
      nonlinear least-squares regression analysis. Univariate and multiple stepwise
      linear regression analyses were used to determine significant relationships
      between demographic characteristics and gentamicin pharmacokinetic parameters.
      Creatinine clearance and postnatal age were the most significant predictors of
      weight-standardized gentamicin clearance (model r2 = 0.86). The relationships
      between patient characteristics and population-based parameters were incorporated
      into the one-compartment Bayesian forecasting model. A second group of 17
      neonates and infants receiving 35 courses of gentamicin therapy were used to
      evaluate the predictive performance of the population-based parameters and a
      Bayesian forecasting model. The population parameters provided accurate
      prediction of steady state gentamicin concentrations throughout multiple courses
      of therapy within the same patient. Bayesian forecasting further minimized the
      mean prediction error (bias) once a set of steady state peak and trough serum
      gentamicin concentrations became available (peak concentrations: -0.062 vs. 
      0.273 mg/l; trough concentrations: -0.006 vs. -0.161 mg/l). The mean absolute
      error (accuracy) was similar for the two sets of parameters. The observed
      accuracy of both the population parameters and Bayesian forecasting suggests that
      monitoring of serum gentamicin concentrations can be kept to minimum in neonates
      and infants.

PMID- 7828457
TI  - Once-a-day administration of amikacin in neonates: assessment of nephrotoxicity
      and ototoxicity.
AB  - Neonates, especially preterms, are known to have low glomerular filtration rates
      (GFR). This may result in elevated trough concentrations during multiple
      administration of aminoglycosides (AGs), potentially leading to nephro- and
      ototoxic reactions. The once-daily administration (q.d.) of AGs has been shown to
      be equally or better tolerated in adults and children than the conventional
      schedules (twice daily, b.i.d.; thrice daily, t.i.d.), while offering potential
      pharmacodynamic and nursing advantages. No data, however, are available for
      neonates. As a consequence, this pilot study was conducted in order to assess the
      tolerance of the once-a-day administration of amikacin in comparison with the
      twice daily dose regimen, in relation to the pharmacokinetics of the drug under
      these two schedules. 22 Male neonates (gestational age > or = 34 weeks; postnatal
      age < or = 2 days) were randomized to receive amikacin (AK) (15 mg/kg/day) q.d.
      (n = 10) or b.i.d. (n = 12) together with ampicillin (50 mg/kg/12 h). AK plasma
      levels were measured at days 1, 3, 5 and 7 of treatment just before the next dose
      (trough level) and 1 h after completion of infusion (peak level) and after 3 and
      6 h only at day 1. Due to the small size of the samples, no difference in
      efficacy could be assessed and was not the aim per se. Glomerular dysfunction was
      assessed by creatinine clearance, and tubular injuries by the urinary excretion
      of proteins (retinol binding protein, beta 2-microglobulin, clara cell protein
      (P1) and microalbumin), enzymes (N-acetyl-beta-D-glucosaminidase, alkaline
      phosphatase, alanine aminopeptidase, and gamma-glutamyltransferase), and total
      phospholipids (TPL) in urine. Ototoxicity was assessed by brainstem auditory
      evoked potentials (BAEPs) at days 0, 3 and 9 of therapy. Eight healthy neonates
      served as controls. All patients showed a normal and similar increase of GFR
      during the first postnatal days. Proteinuria did not increase, but enzymuria and
      TPL increased significantly during the treatment in both AK groups without
      significant difference between groups. BAEPs at day 9 were not significantly
      different between treated and untreated patients. We conclude from this pilot
      study that, in the absence of more toxicity, the q.d. administration of AK in
      neonates of > or = 34 weeks of gestational age may be recommended over its bid
      schedule in view of its potential advantages.

PMID- 7828458
TI  - Chronotropic and dromotropic actions of acetylcholine on the developing fetal
      heart.
AB  - We studied the effect of acetylcholine (ACh), 1 x 10(-8) to 5 x 10(-7) M, on
      electrophysiologic characteristics of the isolated (Langendorf), perfused fetal
      canine heart. ACh induced concentration-dependent decreases in sinoatrial (SA)
      rate and recovery from overdrive pacing and in atrioventricular (A-V) conduction.
      These effects of ACh were greater in mid-gestation than late-gestation hearts.
      The effects of ACh were potentiated by inhibition of acetylcholinesterase by
      neostigmine, 1 x 10(-7) M, in the late- but not the mid-gestation fetal heart.
      Decreasing the pH of the perfusion solution from 7.3 to 6.8 potentiated the
      response to ACh of SA rate and A-V conduction more in mid- than in late-gestation
      hearts. The response to ACh of the late-gestation fetal canine heart is more
      sensitive to cholinesterase inhibition whereas the response of the mid-gestation
      heart is more sensitive to the action of ACh in the presence of acidosis.

PMID- 7828459
TI  - Comparison of CNS adverse effects between astemizole and chlorpheniramine in
      children: a randomized, double-blind study.
AB  - OBJECTIVE: To assess the central nervous system side effects of chlorpheniramine
      and astemizole in children. DESIGN: Prospective, randomized, double-blind cross
      over study. SETTING: Children were recruited from the out-patient allergy clinic
      and from respondents to an advertisement in a local newspaper. The study was
      conducted in the outpatient clinics of the ambulatory care services of the
      Children's Hospital of Eastern Ontario. PATIENTS, PARTICIPANTS: Children 8-16
      years of age, with isolated allergic rhinitis or hay fever, were eligible for the
      study. We excluded children with: (1) chronic conditions (specifically asthma,
      atopic dermatitis, learning disabilities, or current treatment with oral
      corticosteroid medication); (2) known allergy to the study medications; (3)
      recent use of any antihistamine medication. One hundred and three children
      entered the study and 92 completed it. INTERVENTIONS: Children were stratified by
      age and randomly allocated to treatment with one of the two medication sequences.
      Over a period of 13 weeks both groups had 1 week of baseline studies, 3 weeks of
      one study medication, either chlorpheniramine or astemizole, a 6-week wash-out
      period and then 3 weeks of the other study medication for a second treatment
      period. MAIN OUTCOME MEASURES: Attention span (continuous performance test),
      short-term auditory and visual memory (visual aural digit span test), visual
      memory for geometric shapes (Benton visual retention test), motor coordination
      and visual-motor integration (grooved pegboard test), tapping speed and fine
      motor coordination (finger tapping test), physical side effects (such as
      sleepiness and dizziness), and compliance. RESULTS: One hundred and three
      patients were enrolled in the study, 92 (89%) completed the study. There were no
      significant drug effects on the visual retention test and the continuous
      performance test. On the visual aural digit span test, patients treated with
      astemizole scored higher than at baseline. There were no clinical or statistical
      differences in adverse effects between the two medications or between each
      medication and baseline. CONCLUSIONS: The two antihistamines studied had no
      adverse effects on the performance of children.

PMID- 7828460
TI  - [Vaccinations in adulthood].

PMID- 7828461
TI  - [Second malignancy in patients with Hodgkin disease in full remission. Interim
      results].
AB  - Among 345 patients with Hodgkin's disease (HD) in full remission and followed for
      a mean of 7.2 years (11 months-26 years) since the initial diagnosis, 33 were
      found to have a second malignancy. The cumulative incidence after 10 years was
      13.5%, after 15 years 21%. Non-Hodgkin lymphoma was the most frequent (n = 7),
      followed by bronchial carcinoma (n = 5) and acute myeloid leukaemia (n = 3).
      There was a definitely increased risk in elder patients (P < 0.001) and in those
      who had had a splenectomy. There was no demonstrable effect of type of therapy,
      primary stage and frequency of recurrence. It is concluded that patients with
      Hodgkin's disease should have life-long oncological follow-up. This preliminary
      study is being extended into a multicentre investigation of a larger number of
      patients.

PMID- 7828462
TI  - [Brachial plexus lesions and rhabdomyolysis following heroin abuse. Indications
      for an immunological cause].
AB  - On the morning after taking alcohol in large amounts together with intranasal
      heroin, a 25-year-old man experienced pain, swelling and blistering in both arms
      together with right brachial plexus paresis. Creatine kinase (1930 U/l), acute
      phase proteins and IgE (238 IU/ml) were elevated. The pain was largely relieved
      by guanethidine block (given once only), and the swelling and blisters responded
      to methylprednisolone (80 mg daily for 7 days, then gradually reduced). Function
      returned in the lower division of the brachial plexus within ten days, but the
      upper division was still paretic 2.5 months later. After injecting heroin
      intravenously, a 27-year-old man woke up next morning with fever (39 degrees C)
      and proximal flaccid paralysis of the right arm. In addition to leucocytosis
      (25,600/microliters), creatine kinase was raised to 28,890 U/l and pANCA to a
      titre of 1:50 (antineutrophil cytoplasm antibody, perinuclear fluorescence
      pattern). The cerebrospinal fluid showed increases in cell count (15/microliters)
      and protein (73 mg/dl). Acute renal failure supervened after two days but was
      successfully treated. The paresis was still present at four months, though
      improved. A 21-year-old woman developed an upper brachial plexus lesion after
      attempting suicide with intravenous heroin accompanied by flunitrazepam (20 mg by
      mouth) and a bottle of whisky. She had raised levels of C-reactive protein (12
      mg/dl) and IgM (4.0 milligrams). The paresis cleared up within six weeks without
      specific therapy. In view of the immunological abnormalities it seems possible
      that the immune system was involved in the pathogenesis of the plexus lesions and
      the rhabdomyolysis.

PMID- 7828463
TI  - [Pyrimethamine-sulfadiazine resistant cerebral toxoplasmosis in AIDS].
AB  - A 48-year-old man with known HIV infection for 4 years was admitted with a 2-week
      history of increasing brachio-facial paraesthesiae of the left side of the body
      and pains in the head and neck. Physical examination also showed discrete slowing
      of mental activity and oral candidiasis. Toxoplasmosis serology showed a low
      titre with a borderline IgM titre. Cranial computer tomography showed two
      confluent contrast medium concentrating foci in the region of the head of the
      caudate nucleus and the right internal capsule. Because toxoplasmosis
      encephalitis was suspected, treatment was started with sulfadiazine (1 g four
      times daily), pyrimethamine (25 mg four times daily), folic acid (15 mg daily)
      and dexamethasone (8 mg three times daily). After 19 days of treatment there was
      no clinical improvement, and a check CT scan showed worsening with increased
      oedema of the cerebellar medulla, compression of the lateral ventricles and a mid
      line shift of 5 mm. Since the Sabin-Feldman test titre had increased, and there
      was no evidence to suggest a lymphoma or a viral or fungal infection,
      toxoplasmosis resistant to standard therapy was postulated, and treatment was
      started with clindamycin (600 mg three times daily) and pyrimethamine (25 mg four
      times daily). The clinical features subsided within 4 days. A further check CT
      scan 14 days later showed almost complete resolution.

PMID- 7828464
TI  - [Opiate action via opiate receptors].

PMID- 7828465
TI  - [Spinal application of opiates].

PMID- 7828466
TI  - [Molecular basis of tumor formation. Significance for the diagnosis of malignant
      diseases].

PMID- 7828467
TI  - [Successful plasmapheresis in severe diltiazem poisoning].

PMID- 7828468
TI  - [Excretion of tubular marker in diabetic nephropathy. Effect of conversion enzyme
      inhibition].

PMID- 7828469
TI  - [Fibrin gluing of ulcer hemorrhage. Modification of therapy concept needed].

PMID- 7828470
TI  - [How do medical students evaluate the significance of various teaching
      arrangements for medical education?].

PMID- 7828471
TI  - Vocal fold varicosities and pain on phonation.

PMID- 7828472
TI  - Cavernous hemangioma of the tympanic membrane.

PMID- 7828473
TI  - Endoscopic view of exposed vital structures following sphenoethmoidectomy.

PMID- 7828474
TI  - A neural network approach to the prediction of pure tone thresholds with
      distortion product emissions.
AB  - Distortion Product Emission (DPE) growth functions, demographic data, and pure
      tone thresholds were recorded in 229 normal-hearing and hearing-impaired ears.
      Half of the data set (115 ears) was used to train a set of neural networks to map
      DPE and demographic features to pure tone thresholds at six frequencies in the
      audiometric range. The six networks developed from this training process were
      then used to predict pure tone thresholds in the remaining 114-ear data set. When
      normal pure tone threshold was defined as a threshold less than 20 dB HL,
      frequency-specific prediction accuracy varied from 57% (correct classification of
      hearing impairment at 1025 Hz) to 100% (correct classification of hearing
      impairment at 2050 Hz). Overall prediction accuracy was 90% for impaired pure
      tone thresholds and 80% for normal pure tone thresholds. This neural network
      approach was found to be more accurate than discriminant analysis in the
      prediction of pure tone thresholds. It is concluded that a general strategy
      exists whereby DPE measures can accurately categorize pure tone thresholds as
      normal or impaired in large populations of ears with purely cochlear hearing
      dysfunction.

PMID- 7828475
TI  - Lyme disease: a review for the otolaryngologist.
AB  - Lyme disease is an important consideration in the differential diagnosis of
      patients seen by the otolaryngologist. Facial paralysis is the most common sign.
      The otolaryngologist may also see patients with temporal mandibular joint pain,
      cervical lymphadenopathy, facial pain, headache, tinnitis, vertigo, decreased
      hearing, otalgia and sore throat. The incidence is increasing and known to be
      endemic to certain areas of the United States and abroad. This paper reviews the
      various ways Lyme disease appears to the otolaryngologist. Three cases along with
      a discussion including epidemiology, vector, animal host relationship, clinical
      manifestations and pathophysiology are included. The literature is reviewed and
      the treatment discussed.

PMID- 7828476
TI  - Lingual tonsil causing airway obstruction.

PMID- 7828477
TI  - Functional-anatomic correlation of eustachian tube obstruction related to the
      adenoid in a patient with otitis media with effusion: a case report.
AB  - Prospective randomized clinical trials have shown modest but significant
      reductions in morbidity from otitis media with effusion following adenoidectomy.
      However, the precise role of the adenoid in the pathogenesis of otitis media with
      effusion remains unknown. Some authors have hypothesized that the adenoid may
      compress or obstruct the Eustachian tube lumen, thereby causing middle ear
      underpressures and subsequent effusion formation. Functional-anatomic correlation
      for this theory is lacking. Herein, we present a single case of a pediatric
      patient with otitis media with effusion and manometrically proven active and
      passive Eustachian tube obstruction which was relieved by adenoidectomy.
      Photographic anatomic correlation is presented.

PMID- 7828478
TI  - Double maxillary antrum as a cause of maxillary sinus mucocele.
AB  - We report a rare case of a mucocele occurring in a naturally compartmentalized
      maxillary sinus in a 50-year-old woman. Sinus computerized tomography (CT) showed
      the antrum to be divided by a vertical bony septum, producing a mucocele within
      an isolated and non-draining anterolateral compartment. Accidental trauma to the
      thin bony shell precipitated rapid swelling of the pre-existing mass, leading to
      her initial consultation. A wide sublabial surgical approach allowed complete
      excision with a good cosmetic result.

PMID- 7828479
TI  - Solitary malignant schwannoma invading the hypoglossal nerve.

PMID- 7828480
TI  - Cephalic zoster with laryngeal paralysis.
AB  - Herpes zoster reactivaction in the head and neck region is often associated with
      multiple cranial neuropathies, the most common one being facial paralysis.
      Laryngeal paralysis has also been occasionally reported with zoster infection. We
      present two such cases, and discuss the relevant literature on the
      pathophysiology, evaluation and management of this disease. Recent advances in
      antiviral therapy have allowed for specific medical treatment, thus making it all
      the more imperative to suspect zoster, even in clinically atypical cases. We
      suggest aggressive treatment with intravenous acyclovir for cephalic zoster
      complicated by vocal cord paralysis.

PMID- 7828481
TI  - Balancing the nasal tip height with a potential polybeak.

PMID- 7828482
TI  - Cross-promoting--swapping patients.

PMID- 7828483
TI  - Adenoidotonsillectomy.

PMID- 7828484
TI  - Adverse reactions to foods.

PMID- 7828485
TI  - Turbinate injections.

PMID- 7828486
TI  - Attic cholesteatoma.

PMID- 7828487
TI  - The benefits of cochlear implants.

PMID- 7828488
TI  - The efficiency of partial resection of the inferior turbinate.

PMID- 7828489
TI  - Surgery for peptic ulceration.

PMID- 7828490
TI  - Partial gastric resection for peptic ulcer--comparison of the effect of variant
      reconstructive procedures on gastric emptying, gastric acid secretion and gastrin
      release in the early postoperative period I. Roux-en-Y and Billroth-II
      gastroenteroanastomosis.
AB  - Fourteen patients subjected to partial gastric resection with vagotomy and a
      gastroenterostomy (Roux-en-Y, in 11 patients and of Billroth type-II in 3)
      underwent examinations of the gastric emptying (GE) of a radiolabelled solid
      meal, as well as of gastric acid and gastrin secretion before surgery and/or
      within 5.5 weeks postoperatively. The surgery resulted in a significant delay in
      GE-the median T1/2 nearly doubted from 77 min before to 151 min after the
      operation (p < 0.01). The GE pattern did not, however, change significantly, as
      reflected by a median curve shape parameter S amounting to 1.05 and 0.87 before
      and after the surgery, respectively. The Roux-en-Y reconstruction brought about a
      pronounced delay in GE with T1/2 exceeding the border of the mean T1/2 + 2SD of
      healthy controls in 7 (64%) out of 11 patients. On the other hand, no one of the
      B-II operated patients had a slowed GE. The basal and pentagastrin-stimulated
      gastric acid secretion was decreased by an average of 71% (from 6.2 +/- 0.7 to
      1.8 +/- 0.6 mmol h-1, p < 0.001) and 82% (from 25.2 +/- 3.0 to 4.4 +/- 1.2 mmol h
      1, p < 0.001), respectively. The surgery did not affect the fasting serum gastrin
      concentration (53.2 +/- 4.9 pre- vs 51.0 +/- 11.5 ng.l-1 postoperatively),
      whereas the postprandial gastrin release decreased significantly-AUC0-120: 9838
      +/- 1377 ng.l-1 min before and 6863 +/- 1024 ng.l-1 min after the operation, p <
      0.01.

PMID- 7828491
TI  - Partial gastric resection for peptic ulcer--comparison of the effect of variant
      reconstructive procedures on gastric emptying, gastric acid secretion and gastrin
      release in the early postoperative period II. Billroth-I gastroduodenostomy and
      comparison versus gastroenteroanastomotic procedures.
AB  - Gastric emptying (GE) of a radiolabelled solid meal, gastric acid secretion and
      gastrin release was measured before and/or by 91/2 weeks postoperatively in 12
      patients with partial gastric resection supplied with Billroth-I
      gastroduodenoanastomosis and usually (n = 10) with truncal vagotomy [B-1+(VT))].
      The results obtained were compared to those derived from another study involving
      14 patients with partial gastric resection supplied with a gastroenterostomy (of
      Roux-en-Y type in 11, and Billroth-II type in 3 subjects) and truncal vagotomy
      [Roux(B-II)+VT]. The B-I+(VT) procedure affected significantly neither the
      overall GE (the median T1/2 was 75 min before and 95 min after the surgery) nor
      the GE pattern-the median curve shape parameter S was 0.73 before and 1.07 after
      the operation. The basal and pentagastrin-stimulated gastric acid secretion was
      reduced by an average of 79% (from 8.6 +/- 2.5 to 1.8 +/- 0.5 mmol h-1, p < 0.05)
      and 77% (from 22.0 +/- 2.8 to 5.0 +/- 1.5 mmol h-1, p < 0.05) after the B-I+(VT),
      respectively. Moreover, after the B-I+(VT) a decrease in the fasted serum gastric
      concentration (78.3 +/- 17.0 before vs 62.4 +/- 6.9 ng l-1 after the surgery) and
      in the postprandial gastrin release (AUC0-120: 11716 +/- 2482 ng l-1 min before
      vs 9753 +/- 1183 ng l-1 min after the surgery) was found; the relevant
      differences were, however, statistically not significant. In patients with a
      preoperatively normal GE, a markedly slowed GE (T1/2 above the limit of the mean
      T1/2 +2SD in healthy controls) was found in 5 out of 8 (62%) patients after the
      Roux-en-Y procedure, and only in 1 out of 7 (14%) patients after the B-I or B-II
      procedure. With regard to the postoperative data, the Roux (B-II)+VT resulted in
      lower gastric acid secretion and gastrin release than the B-I+(VT) procedure but
      the relevant differences were statistically not significant.

PMID- 7828492
TI  - Operative management of achalasia of the oesophagus.
AB  - Twenty patients with achalasia of the oesophagus were managed in one thoracic
      surgical unit over a period of seven years. Eighteen of these were aged 16 to 40
      years. There was a female:male ratio of 2:1. Dysphagia to both solids and liquids
      with diffuse bilateral parotid gland enlargement were the most common clinical
      features. All the patients had an oesophagomyotomy without an additional anti
      reflux procedure. There was no mortality. The trans-thoracic approach for
      oesophagomyotomy was associated with better results without complications of
      gastro-oesophageal reflux. This approach is recommended and an additional routine
      anti-reflux procedure at the same sitting may be unnecessary.

PMID- 7828493
TI  - Cutaneous leishmaniasis in Kenya: Sergentomyia garnhami (Diptera Psychodidae), a
      possible vector of Leishmania major in Kitui District: a new focus of the
      disease.
AB  - Investigations on phlebotomine sandflies in Tseikuru, Kitui District, Kenya were
      carried out to determine the vectors of Leishmania major. Sandflies were trapped
      from animal burrows over a period of one year using castor oil-smeared sticky
      traps. Nineteen phlebotomine sandfly species were identified and their prevalence
      in this habitat determined. Dissections on the parous sandflies resulted in the
      isolation of Leishmania parasites from Phlebotomus martini and Sergentomyia
      garnhami. The isolated parasites were cultured in NNN medium and were
      consequently mass cultured in RPMI medium for biochemical characterisation. The
      parasites from S. garnhami were typed as Leishmania major.

PMID- 7828494
TI  - Evaluation of alpha-1-antitrypsin, alpha-1-acid glycoprotein and pre albumin in
      serum of Ghanaian subjects.
AB  - Serum alpha-1-antitrypsin (AAT) and alpha-1-acid glycoprotein (AAGp): pre albumin
      ratio, sensitive markers for liver damage were evaluated in 32 apparently healthy
      Ghanaian subjects. Eighteen of the subjects (Group 1) had Serum AAT values (mean
      +/- SD) of 151.9 +/- 18.6 mg/dl while 14 (Group 2) had 209.3 +/- 13.6 mg/dl.
      AAGp: pre albumin ratio were respectively 1.03 +/- 0.79 and 2.76 +/- 1.00. The
      difference between the two groups with respect to the AAT and AAGp: pre-albumin
      ratio is highly significant (p < 0.01). No correlation was seen between these
      proteins and serum gamma glutamyltransferase (GGT) or alanine aminotransferase
      (ALT) levels. The GGT and ALT levels were normal in the Group 1 subjects but
      elevated in some of those in Group 2. It is suggested that the obtained higher
      AAT values and AAGp: pre albumin ratio might be abnormal for Ghanaian subjects
      and that these proteins should be monitored to facilitate early detection of
      liver injury. This might be important for population groups living in geographic
      areas where environmental agents that cause liver damage are common.

PMID- 7828495
TI  - Needs assessment in demand reduction programmes with special reference to African
      countries.
AB  - Drug abuse trends in African countries indicate an urgent need for intensive
      demand reduction packages to address the problem. However, enormous obstacles
      exist as many of these countries lack the necessary resources to assess the basic
      needs essential to implementing empirically-based and cost-effective programmes.
      This article reviews general principles of needs assessment and provides some
      practical guidelines appropriate to the African context. Effective cooperation
      and collaboration at the local, national and the international level is needed to
      attain the desired goals of needs assessment these countries.

PMID- 7828496
TI  - The changing patterns of Campylobacter jejuni/coli in Lagos, Nigeria after ten
      years.
AB  - One hundred and forty-five stool samples from children with diarrhoea at various
      health centres in Lagos were investigated for Campylobacter jejuni/coli. These
      organisms were isolated from 24 samples (16.5%). They were later biotyped as 23
      C. jejuni and one C. coli. Previous studies (3,6) recorded isolation rates of
      5.2% and 11% respectively. No Campylobacter species was isolated from 100 control
      patients who did not have diarrhoea. Diarrhoea due to Campylobacter jejuni/coli
      is still common in males, and the ration of males to females is still 2:1 but the
      isolation rate is now 11.7%:4.8%. All the isolates of Campylobacter jejuni are
      still from children under two years of age. Campylobacter jejuni biotype 1
      accounted for 52.5% in an earlier study (18), but accounted for 87.5% in this
      study. Serogroup 29(70.8%) was the commonest in this study, whereas serogroup
      36(20.7%) was very common in an earlier study(18). Erythromycin, which is the
      drug of choice for the treatment of campylobacter enteritis, had 82% sensitivity
      to the organism(6) but in the present study only 20.8% of the isolates were
      sensitive to the antibiotic. Betalactamase production was detected in 12.5% of
      the isolates as against 6.4% earlier reported(17).

PMID- 7828497
TI  - Ocular findings in leprosy patients in Nigeria.
AB  - An ophthalmic assessment of patients in four out of the five leprosy clinics in
      Anambra State, eastern Nigeria, showed that 63% had ocular disease and 43.5% had
      sight-threatening disorders. Most of the problems occurred in multibacillary
      leprosy patients. The blindness rate of (8.7%) is nearly 10 times higher than
      that within the general population in area. The causes of blindness were
      cataract, exposure keratopathy and uveitis. Some patients also had glaucoma and
      chorioretinal lesions. Eye health service within the leprosy control service in
      the area is non-existent. The importance of giving priority to blindness
      prevention in leprosy patients in the area is emphasised.

PMID- 7828498
TI  - Use of cold-chain to assess vaccine exposure to adverse temperatures in rural
      Tanzania.
AB  - A study was carried out in Tabora region to determine the magnitude of exposure
      of vaccines to adverse temperatures using the Cold Chain Monitors (CCMs). Except
      for refrigerators in the regional hospital, almost all refrigerators were found
      to be exposed to adverse temperature. The RAK type of refrigerators were found to
      be more exposed to adverse temperature than the RCW type. While an alternative
      type of refrigerator suitable for tropical countries is being sought there is a
      need of focusing more attention on improving cold chain system in the peripheral
      facilities.

PMID- 7828499
TI  - Intestinal helminthic infections in the southern Rift Valley of Ethiopia with
      special reference to schistosomiasis.
AB  - Nineteen communities located in the southern part of the Ethiopian Rift Valley
      were surveyed for S. mansoni infection and other helminth parasites of man. S.
      mansoni infected individuals were recorded in 11 communities and human prevalence
      reached more than 10% in 4 of them. The snail intermediate hosts were
      Biomphalaria pfeifferi in the lower Omo River basin and B. sudanica in the Rift
      Valley lakes. Other parasites encountered included A. lumbricoides (11.2%), T.
      trichiura (10.3%), hookworms (25.3%), Taenia sp. (8.1%), Strongyloides sp.
      (2.9%), H. nana (0.8%), Trichostrongylus sp (0.3%) F. hepatica (0.1%) and E.
      vermicularis (0.1%). In some communities the prevalence of hookworms, A.
      lumbricoides and T. trichiura reached 70%, 66.6% and 60%, respectively. A strong
      association (r = 0.9) was observed between altitude and parasite prevalence and
      burden. In nine communities located below 1200 metres, infected individuals
      harboured nearly two or less the number of parasite species while in 10
      communities located at altitude above 1200 metres, multiple infection with three
      or more parasites reached as high as 53.2%. Similarly, the average parasite
      species per infected person ranged from 0 to 1.4 in the nine communities located
      at lower altitudes and from 1% to 2.6% in the 10 communities located at higher
      altitudes. By ages, both prevalence and multiparasitism are significantly in
      favour of those below 20 years of age (P < 0.005) although hookworms are
      prevalent in a wider age range. The widespread occurrence of intestinal
      schistosomiasis in the southern Rift Valley and the epidemiological pattern of
      other intestinal helminth parasites of man in this section of the Valley are
      discussed.

PMID- 7828500
TI  - Is one year follow-up justified in kala-azar post-treatment?
AB  - Sixty-five patients, 51 males and 14 females, with clinical and parasitological
      evidence of visceral leishmaniasis were initially treated as follows: 44.6% were
      on intravenous sodium stibogluconate (pentostam) 20 mg/kg/d for 30 days, 35.4%
      was on a combination of pentostam as above and allopurinol 21 mg/kg/d in three
      divided doses for 30 days while 20% was on pentostam 10 mg/kg thrice/d
      intravenously for 10 days. All patients were parasitologically negative by the
      end of their respective treatment regimen. All patients were reviewed at 2
      months, 6 months, and 12 months periods in order to evaluate the relapse rates
      and optimal follow-up period. Thirteen patients (20%) relapsed at 2 months and
      one patient (1.5%) relapsed at 6 months follow-up periods respectively. There was
      no relapse between 6 months and 12 months follow-up period. The mean liver and
      spleen sizes in responders showed a dramatic reduction at 2 months follow-up and
      thereafter a gradual reduction occurred in the next 10 months. Weight gain
      continued throughout the year. Apart from platelet count which showed a sustained
      high level from discharge to 12 months follow-up, the peripheral blood indices
      stabilized from 2 months follow-up. Relapses were retreated until
      parasitologically negative twice and then followed up, for a period of 12 months.
      At follow-up the liver and spleen sizes reduced gradually in the next 12
      months.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7828501
TI  - Dose adequacy in measles vaccinations in Tabora region, Tanzania.
AB  - A study was carried out in Tabora region between July 1991 and September 1991,
      with the aim of determining the adequacy of measles vaccine given to children in
      Maternal Child Health clinics. Measles vaccine dose used per child was found to
      be 0.485 ml, which is about 0.385 ml when wastage due to removal of air bubbles
      is subtracted. Workers in the field need to be trained on the exact volume of
      vaccine required to be drawn into the syringe before vaccination, to ensure that
      a dose measuring exactly 0.5 ml of vaccine is injected to a child.

PMID- 7828502
TI  - Smell acuity for acetone and its relationship to taste ability to
      phenylthiocarbamide in a Nigerian population.
AB  - Acetone smell sensitivity and phenylthiocarbamide taste sensitivity thresholds
      have been measured simultaneously for 970 Nigerians (542 males and 428 females)
      using modified sorting techniques. The distribution was bimodal in both cases and
      the frequency of subjects with high smell acuity for acetone was 9.6% while that
      of non-tasters was 12.60% with a gene frequency, as computed by maximum
      likelihood methods, of 0.355 +/- 0.015. Females showed a higher frequency for
      smell sensitivity to acetone but a slightly lower frequency of non-tasters
      compared to males. Acetone smell sensitivity and PTC with high smell acuity for
      acetone were tasters while 30.28% of subjects least sensitive taste ability
      decreased with age in the overall population. All the subjects least sensitive to
      acetone were non-tasters, a significantly higher proportion than in the overall
      population. The correlation between acetone smell acuity and phenylthiocarbamide
      taste ability demonstrates a strong allelic association. All the 94 individuals
      with high smell acuity for Acetone were tasters for phenylthiocarbamide.

PMID- 7828503
TI  - Lower limb trauma: a review of 40 cases treated at the regional burns and plastic
      surgery unit, Merseyside, England.
AB  - This is a review of 40 patients with lower limb trauma that required
      reconstruction, treated at Mersey Regional Plastic Surgery and Burns Centre
      during the year 1989. 73% had bone involvement while there was soft tissue injury
      only, in 27%. Seven patients (18%) had the affected limb amputated. Of the rest,
      6 were treated with skin grafts only, 13 with local flaps and 14 with free flap
      reconstruction. The soft tissue healing time was least in patients who had free
      flaps. The time taken by skin and bone to heal and the average duration of
      hospitalisation was also less in cases that had early management compared to
      those who had delayed and late treatment. Early reconstruction in severe lower
      limb trauma is desirable and cost effective.

PMID- 7828504
TI  - Ocular morbidity at a small eye unit in Jimma town, south western Ethiopia: a
      three year analysis.
AB  - A total of 10,299 new cases of eye diseases were seen in the past three years at
      Jimma Eye Unit. Conjunctivitis, trachoma, cataract, and refractive errors, were
      the leading causes of ocular morbidity accounting for 35.5%, 16.8%, 10.6% and
      9.7% of the cases respectively. 28.3% of the trachoma cases had trichiasis and/or
      entropion. Increased activity in primary eye care in general and, provision of
      entropion surgery, availability of low-cost eye glasses and the expansion and
      improvement of the eye unit are recommended to effect a better ophthalmic service
      in the region.

PMID- 7828505
TI  - Allergies and skin testing: a Nairobi experience.
AB  - A prospective study of 72 consecutive patients with symptoms of allergy is
      presented. Patients aged 20-39 years formed the bulk of the study population
      (55.6%). Most patients had allergic rhinitis (48.6%); bronchial asthma and atopic
      dermatitis occurred in 29 patients (40.3%) each. Drug allergies were found in 22
      patients (30.6%), urticaria in 15 (20.8%), food allergies in 13 (18.1%), contact
      dermatitis in 10 (13.9%) and allergic conjuctivitis in 6 patients (8.3%). In many
      cases more than one allergic condition appeared simultaneously. Skin and prick
      tests and skin patch tests were done on 46 (63.9%) and 65 (90.3%) patients
      respectively. Soaps were most frequently implicated in positive reactions
      (75.0%); D. pteronyssinus, drugs, animal dander and foods gave positive reactions
      in 40.3%, 30.6%, 19.4% and 18.1% respectively. The need to have a high index of
      suspicion towards allergic conditions, especially extrinsic bronchial asthma, is
      stressed.

PMID- 7828506
TI  - Residual facial deformity resulting from cancrum oris: a case report.
AB  - Cancrum oris cases are occasionally treated in various hospitals in Kenya.
      Despite this, only one case has been reported in literature. Besides, no
      epidemiological or treatment studies of cancrum oris has been carried out in
      Kenya. We report an unusual case of a 17 year old Kenyan female with oral
      cutaneous fistula and tissue atrophy on the left cheek following cancrum oris
      infection in childhood. Since most cancrum oris cases are a sequela of acute
      necrotizing gingivitis (ANG), prevention of cancrum oris can be achieved by early
      and prompt remedial measures once a diagnosis of ANG is established. Failure to
      do this might lead to cancrum oris with its attendant disfiguring complications
      some of which might be impossible to treat in developing countries where the
      requisite personnel is lacking or inadequate.

PMID- 7828507
TI  - [Schizophrenia or affective disorder?].

PMID- 7828508
TI  - [Endogenous affective disorder, seasons of birth and photoperiodicity].
AB  - In a retrospective study, we compared the months of birth of 3,106 psychiatric
      inpatients to those of 1,943 surgical patients collected during the same period
      1981-1991 in the same hospital, and of a sample of 10,003,572 births in France in
      1977-1989. DSM III-R categories were modified so to allow a comparison with
      former studies, and psychiatric patients were distributed among seven categories:
      Bipolars (N = 294), Unipolars (N = 287), Neurotic-reactive depressions (N = 582),
      First Major Depressive episode (N = 214), Schizophrenia (N = 244), Schizo
      Affectives (N = 52) and Other Diagnosies (N = 1,433). Months of birth were
      grouped in quarters and semesters, according to the usual calendar, but also to
      temperature and the photoperiodic cycle. The main results were: 1. A seasonnality
      of births in the General Population sample, with a spring maximum (p < 0.001). 2.
      An absence of deviation from the general population and the surgical sample among
      Neurotic-reactive Depressions and Other Diagnoses. 3. A deviation from the
      general population and from other comparison groups (surgical cases and Other
      Diagnoses) among Unipolars and First Major Depressive Episodes (most of those
      being late episodes), with a significant excess of births during the "dark" or
      "cold" season of the year, especially around the winter solstice. The Bipolar
      group followed the same tendency, though to a lesser degree and for subjects born
      before 1940 only. The most significant results were found among Unipolars, which
      differ from the general population either by quarters (p < 0.0005) or by
      semesters (p < 0.0005) and from surgical cases by quarters (p < 0.01) and by
      semesters (p < 0.001). The results were similar for First Major Depressive
      episodes, although this category was theoretically "anosological". As the median
      age was high in this category, it might group a number of late depressive
      episodes, near to "involutionnal melancholia". Thus, our results seem to be
      relevant to the traditional endogenous-psychogenetic dichotomy, with a "cold" or
      "dark" seasonnality of births in the first case, and no particular seasonnality
      in the second case. Some former studies showed the same results, but the most
      significant deviation was found in mania. Our results cannot be explained by
      differences in the sex-ratio among the categories, and only partially by an age
      incidence effect or an age-cohort effect.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7828509
TI  - [Seasons of birth of schizophrenic patients. Retrospective study of a
      hospitalized population in Tunisia].
AB  - Epidemiological research concerning the seasons of births of schizophrenics show
      for the greatest part that there's an excess of births in winter and in the
      beginning of spring. Research about the environmental theories of schizophrenia
      suggest that there would exist one or many seasonal environmental factors
      affecting the foetus and the neonate, and which would be likely to increase the
      risk of a subsequent development of schizophrenia. As no research concerning this
      subject have been published so far in Africa, the writers propose to study the
      distribution of births of a population of schizophrenics born in Tunisia in
      comparison to the general population and to compare it to a group of patients
      hospitalized because of major affective disorders. The results achieved show a
      significant decrease in the number of schizophrenics births during the third
      trimester and an excess of births during the month of october, the risk being
      greater in the case of disorganized schizophrenia. The greater risk for people
      born in october to develop subsequently schizophrenia is not found in the case of
      major affective disorders but it is found rather in the case of schizo-affective
      disorders. More over, we notice a decrease in the number of births during the
      month of July for the patients presenting major affective disorders and for those
      presenting schizo-affective disorders. Results seem to demonstrate that there
      would exist seasonal environmental factors specific to North Africa which are
      likely to affect the subsequent appearance of schizophrenic disorders. A
      particular interest should be given to viral infectious to enteroviruses which
      are responsible for summer diarrhea in Tunisia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7828510
TI  - [Application of a structured interview guide adapted to 4 depression scales].
AB  - The authors present the development and the application of a structured interview
      guide for 4 depression scales: Hamilton Depression rating scale 17 items (HDRS
      17), Montgomery-Asberg Depression rating scale (MADRS), Widlocher Depressive
      Retardation Scale and also a fourth scale designed to evaluate the symptoms other
      than depression core symptoms (based on Depression and mania rating scale of P.
      Pichot). The final version of the guide was tested with 60 french depressed
      inpatients. This guide provides clinical information that permits the rating of
      the 4 scales in approximatively 45 minutes.

PMID- 7828511
TI  - [Comparison of 2 depression scales and their relationship with negative and
      akinetic symptoms in stabilized schizophrenic patients].
AB  - Since the Bleuler's early writings, studies in schizophrenia have often shown a
      frequent occurrence of depression in the context of schizophrenia and also its
      implications for the morbidity and mortality of schizophrenic patients. The wide
      variability in the prevalence of depression (between 7 to 70% in post-psychotic
      period) is due in part to the difficulty in clearly separating depressive
      symptoms from akinesia induced by neuroleptic or negative symptoms and to the
      lack of a valid assessment of depressive symptoms in schizophrenic patients.
      Under these conditions, a better understanding of depressive symptomatology in
      schizophrenia seems to be necessary to go further in this area of research with
      clinical and therapeutical purposes. The "Echelle de Ralentissement Depressif"
      (ERD, Widlocher, 1983) was studied in a sample of 53 schizophrenic patients to
      determinate whether ERD composed of three subscores (motor, ideic and subjective)
      could be able to evaluate the subjective depressive symptomatology and whether
      its measure would be independent of negative symptoms or akinesia. Pearson's
      correlations and correlations with variables partialled out were used to compare
      ERD to Montgomery and Asberg Depression Rating Scale (MADRS, 1979) and to
      establish their relationship with Positive And Negative Syndrome Scale (PANSS<
      Kay, 1987) and an Extrapyramidal Symptom Rating Scale (ESRS, Chouinard & Ross
      Chouinard, 1980). Fifty three in or outpatients (35 males and 18 females, mean
      age +/- standard deviation = 38.26 +/- 9.82) were evaluated in a stable condition
      (i.e., when the psychotic symptomatology and the neuroleptic treatment have been
      stabilized since 4 weeks). According to DESM III-R criteria, 49 patients met the
      diagnosis of schizophrenia (2 schizoaffective disorders and 2 schizophreniform
      disorders).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7828512
TI  - [Prevalence and risk factors of suicide and attempted suicide].
AB  - Suicide provocates 0.5 to 1% of the deaths in France. Every year, more than
      12,000 people die by suicide. In France, the annual incidence rate of suicide is
      21/100,000. Among young people (15 to 24) suicide rate is 13.9/100,000 in men and
      4.2/100,000 in women. Methods of suicide are hanging (38%), firegun (23%),
      overdose (13%) and drowning (10%). Among the suicides, most subjects are
      unmarried, live alone and more often in Paris. Suicide is more frequent during
      the day than during the night, in the beginning of the week, in summer and in
      spring. Suicide rates in France are comparable to those observed in United States
      and Great Britain. Suicide appears to be closely related to psychiatric
      morbidity. Most frequent psychiatric diagnosis in patients who commit suicide are
      depression (64%), alcoholism (15%), schizophrenia (3%) and anxiety (3%). History
      of depression is associated with a 30 fold increase in suicide risk. Globally,
      the annual incidence of suicide among depressives is 1% and 15% of the
      depressives die by suicide. When depressive symptoms are retrospectively
      assessed, it appears that 45 to 70% of patients who committed suicide presented
      depression. Depressives older than 50 and patients with history of attempted
      suicide have a greater risk of suicide. Among schizophrenics, frequency of
      suicide is 10 to 13%. Suicide are more frequent during the first ten years of the
      illness. In patients presenting panic disorder, frequency of suicide is variable
      according to the authors, between 30% and 3%. Attempted suicide are much more
      frequent than suicide. The annual rate is 162/100,000 in men and 265/100,000 in
      women.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7828513
TI  - [Reaction time measures in depressed patients].
AB  - The work presented below is enclosed in a research on depressive retardation in
      children. It deals with the measurement of reaction time to sensori stimuli
      (visual or auditory) among children from 7 to 13 year old. Patients with major
      depressive episode were presented twice, before medication and at their
      discharge. The assessment which is performed to the nearest thousandth of a
      second thanks to a program developed on micro computer includes 5 test
      situations: 1. simple visual stimulation; 2. simple auditory stimulation; 3.
      choice situation between visual and auditory stimulation; 4. unlocated visual
      stimulation; 5. choice situation between two different visual stimulations.
      Generally speaking the best scores are logically achieved for the simple auditory
      tests followed by the simple visual test. The highest scores almost
      systematically appear for the test offering the choice between two different
      visual stimulations. For each of the five tests the values are always correlated
      between the two passation periods. These correlations mean that the passation
      time depends on each child. Those who achieved "good scores" in the depression
      phase before medication are the same who achieve good scores at their discharge
      and vice versa. These performances have no relation either with the age of the
      children. The analysis of the results brings out two factors: For simple stimuli
      tests, performances do not vary between the two passation periods and therefore
      show a motor normal function. On the other hand, for tests which involve a choice
      (and therefore decision making) before medication children react significantly
      more slowly than after improvement.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7828514
TI  - [Automatic information processing, the frontal system and blunted affect. From
      clinical dimensions to cognitive processes toward a psychobiological explanation
      of temperament].
AB  - Several theorists have drawn a distinction between automatic and attentional or
      controlled processing. Hasher and Zacks (1979), were the very first to argue that
      effortful processes are reduced under conditions of stress including depression.
      They suggested that, in these conditions, no such deficit occurs in automatic
      processing. Then, Weingartner and co-workers provided some experiments which
      seemed to support such an interpretation of the cognitive dysfunction in
      depressed patients. However, some recent data do not fit with this well admitted
      theoretical framework. The purpose of our article is to try to clarify this issue
      both from a theoretical and from a methodological point of view. First, we make a
      critical review of the most recent results in three fields of experimentation
      related to the "automatic versus controlled" topic: 1) The classical
      neuropsychology of memory which manipulates the level of effort required to
      perform the tasks. Confusion arises when theories at the process level are tested
      with reference to data collected at the task level. The transparency assumption
      could be false: Impairment in an effort-demanding task could be due to a defect
      in automatic processes and it is possible to hypothesize that the more automatic
      processes are deficient, the more controlled processes are saturated and the
      effort demanding task impaired. The emergence of controlled processes could
      depend on the level of automaticity and the regulation of automatic processes
      could be determinant for the ability of the subject to make associations. 2) The
      recent studies on implicit memory in depression.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7828515
TI  - [Can a serotonin uptake agonist be an authentic antidepressant? Results of a
      multicenter, multinational therapeutic trial].
AB  - The classical biochemical hypothesis of depression posits a functional deficit in
      central neurotransmitter systems particularly serotonin (5-HT) and noradrenaline.
      The major role suggested for 5-HT in this theory led to the development of a
      large number of compounds which selectively inhibit 5-HT uptake. Numerous
      clinical trials have demonstrated the antidepressant efficacy of such types of
      serotoninergic agents, supporting 5-HT deficit as the main origin of depression.
      Therefore, everything seemed clear: depression was caused by 5-HT deficit.
      Tianeptine is clearly active in classical animal models predictive of
      antidepressant activity, and is also active in behavioral screening tests: it
      antagonizes isolation induced aggression in mice and behavioral despair in rats.
      Biochemical studies have revealed that in contrast to classical tricyclic
      antidepressant, tianeptine stimulates 5-HT uptake in vivo in the rat brain. This
      somewhat surprising property was observed in the cortex and the hippocampus
      following both acute and chronic administrations. This increase in 5-HT uptake
      has also been confirmed in rat platelets after acute and chronic administrations.
      Moreover, in humans, a study in depressed patients demonstrated that tianeptine
      significantly increased platelet 5-HT uptake after a single administration as
      well as after 10 and 28 days of treatment. The antidepressant activity of
      tianeptine has been evaluated in controlled studies versus reference
      antidepressants. Another study aiming to compare the antidepressant efficacy of
      tianeptine versus placebo and versus imiporamine is presented. 186 depressed
      patients were included in this trial. They presented with either Major
      Depression, single episode (24.6%) or Major Depression recurrent (66.8%) or
      Bipolar Disorder (depressed) (8.6%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7828516
TI  - [Hyponatremia of therapeutic origin. Apropos of a case].
AB  - Recent epidemiologic studies (11) have shown a frequency of 3-5% of hyponatremia
      in chronic psychiatric patients, characterized by headaches, blurry vision,
      weakness, cramps, vomiting and sometimes seizures or coma leading to death. The
      etiopathology of this electrolytic syndrome is still debated and intriguing. Six
      to 17% of hospitalized patients in psychiatry present primary polydipsia, among
      which 25-50% develop hyponatremia. Another cause is the syndrome of inappropriate
      secretion of anti-diuretic hormone, SIADH, which may be due to a number of
      psychotropic drugs as carbamazepine, thioridazine, amitriptyline, desipramine,
      haloperidol, chlorpromazine and fluoxetine (1, 2, 7, 9, 15, 18, 24). These
      medications can be associated with primary polydipsia but not necessarily, and
      the hyponatremia is reversible after discontinuiting the treatment. We describe a
      case of hyponatremia possibly related to clomipramine which has been rarely
      reported in the literature and discuss the relations between hyponatremia,
      psychosis, and SIADH.

PMID- 7828517
TI  - [A misleading depression].
AB  - The present paper relates the case of a young female patient who suffers from
      epilepsy and depressive disorder. The discovery of digestive disturbances
      associated to an anaemia and various tests induces a diagnosis of a coeliac
      disease. Such relationship is unusual with depression and epilepsy. The author
      insists on the fact that a diagnostic cannot fix a person in a unique mode of
      attendance because a disease can mask another one.

PMID- 7828518
TI  - Food irradiation.
AB  - Large amounts of food, perhaps as much as one quarter of the world's agricultural
      production, is lost due to spoilage or contamination by harmful bacteria and
      other parasitic life forms. Food irradiation is an energy-efficient, non-chemical
      method of food processing that can help reduce these huge losses. Properly
      treated, irradiated foods retain their fresh appearance, flavour, and nutritional
      value, while most foods can be pre-packaged before irradiation, reducing the risk
      of recontamination. The technology for food irradiation is now well developed and
      irradiated foods are gaining public acceptance as they become more widely
      available.

PMID- 7828519
TI  - Targeted overexpression of an inactive calmodulin that binds Ca2+ to the mouse
      pancreatic beta-cell results in impaired secretion and chronic hyperglycemia.
AB  - We have previously reported that elevated levels of calmodulin in pancreatic beta
      cells of mice resulted in a unique secretory defect. To determine if this effect
      was due to Ca2+ buffering, a mutant form of calmodulin that has an eight-amino
      acid deletion in the central helix (CaM-8) was used. The mutated calmodulin binds
      Ca2+ normally, but alters the ability to interact with known Ca2+/calmodulin
      activated enzymes. In vitro competition analysis using HIT cell extracts verified
      that in the presence of Ca2+, CaM-8 exhibited at least a 100-fold lower affinity
      for calmodulin-binding proteins than did normal CaM in this model beta-cell.
      Transgenic mice were then generated by targeting the CaM-8 to pancreatic beta
      cells. The CaM-8 mice were normoglycemic at birth, but developed a hyperglycemic
      condition starting at about 6 days of age. This condition was progressive and
      characterized by elevated blood glucose that coincided with reduced levels of
      pancreatic insulin and low circulating serum insulin levels. Hormone measurements
      and immunohistochemical analysis revealed that islets exhibited a nonimmune
      reduction of insulin immunoreactive beta-cells, reduced amounts of insulin, and a
      5-fold higher level of CaM-8 protein relative to normal CaM protein. Perifusion
      assays were used to test the secretion response to glucose. CaM-8 islets
      demonstrated a reduction in first and second phase insulin secretion, which
      became progressively worse with age. Depolarization of the membrane with 50 mM K+
      in the presence of high glucose did not significantly improve secretion.
      Carbachol, which is thought to act in beta-cells through the release of
      intracellular Ca2+ stores and activation of protein kinase-C, restored both
      phases of secretion to normal levels. These results suggest that disruption of
      intracellular Ca2+ homeostasis alone is sufficient to interfere with the insulin
      secretion pathway.

PMID- 7828520
TI  - Thyrotropin-induced hydrogen peroxide production in FRTL-5 thyroid cells is
      mediated not by adenosine 3',5'-monophosphate, but by Ca2+ signaling followed by
      phospholipase-A2 activation and potentiated by an adenosine derivative.
AB  - The production of hydrogen peroxide (H2O2) as an essential process for iodide
      organification is a key reaction in TSH-induced thyroid hormone synthesis. Here
      we characterize the signal transduction pathway involved in TSH-induced H2O2
      production in FRTL-5 thyroid cells. At higher than 1 nM TSH, N6-(L-2
      phenylisopropyl)adenosine (PIA), an adenosine receptor agonist having, by itself,
      no influence on H2O2 generation, potentiated this TSH action, whereas the TSH
      increase and PIA addition reduced cAMP accumulation. RO 20-1724, a
      phosphodiesterase inhibitor, amplified the TSH-induced cAMP accumulation, but did
      not change H2O2 generation in the whole range of TSH used. Ca(2+)-mobilizing
      agonists, GTP and ATP, also induced H2O2 production without stimulating cAMP
      accumulation. Chelation of intracellular Ca2+ markedly inhibited the TSH action,
      but intracellular Ca2+ increases by either thapsigargin or ionomycin mimicking
      it. All of the findings show the participation of Ca2+, but not cAMP, in the
      action of TSH. Desensitization of protein kinase-C (PKC) did not influence the
      receptor-mediated H2O2 production, suggesting the reduced importance of PKC
      activation compared to Ca2+ signaling to the reaction. A rise in intracellular
      Ca2+ independent of receptor activation also induced H2O2 production as well as
      arachidonate release, and both were potentiated by PIA. In addition, inhibitors
      of phospholipase-A2 and the arachidonate metabolic pathway depressed H2O2
      generation, suggesting the participation of an arachidonate cascade in the Ca(2+)
      dependent H2O2 production. Lipoxygenase inhibitors depressed the Ca2+ action
      without influencing arachidonate release, suggesting the involvement of a
      lipoxygenase product(s) of arachidonate in the Ca(2+)-signaling mechanism. In
      conclusion, in FRTL-5 cells, TSH-induced H2O2 production is mediated not by cAMP,
      but by the phospholipase-C/Ca2+ cascade, possibly followed by the Ca(2+)
      dependent phospholipase-A2/arachidonate cascade. PIA amplifies TSH-induced H2O2
      production at the steps of phospholipase-C and phospholipase-A2 activation in a
      pertussis toxin-sensitive manner.

PMID- 7828521
TI  - Osteoblasts mediate insulin-like growth factor-I and -II stimulation of
      osteoclast formation and function.
AB  - Insulin-like growth factor-I (IGF-I) and IGF-II have powerful, well defined
      effects on osteoblastic cells, stimulating their proliferation and inducing
      collagen synthesis, but the role of IGF-I and -II in modulating osteoclast
      differentiation and activity remains unclear. We first examined the bone
      resorptive effects of IGF-I and IGF-II by assessing 45Ca2+ release from neonatal
      mouse calvarial bones. Both IGFs dose dependently stimulated bone resorption,
      with an EC50 of 8 x 10(-9) M for IGF-I and 2 x 10(-8) M for IGF-II. We then
      tested the effects of the IGFs on bone resorption by rat isolated osteoclasts
      cultured on ivory slices. Neither IGF-I nor IGF-II stimulated isolated osteoclast
      activity. However, in the presence of either primary mouse osteoblasts or human
      osteosarcoma MG 63 cells, both IGFs enhanced osteoclast resorptive activity, with
      an EC50 of 5 x 10(-10) M for IGF-I and 10(-9) M for IGF-II. Stimulation was not
      mediated by BALB/c/3T3 cells, a nonosteoblastic cell line. The effects of the
      IGFs were blocked by alpha IR-3, an antibody to the type I IGF receptor, but not
      by beta-galactosidase, a lysosomal enzyme that competes with IGF-II for the type
      II IGF receptor. We then examined the effects of the IGFs on the formation of
      osteoclast-like multinucleate cells (MNCs) in mouse bone marrow cultures. IGF-I
      and -II dose dependently increased the number of tartrate-resistant acid
      phosphatase (TRAP)-positive MNCs, although their effects were less than that of
      1,25-dihydroxyvitamin D3 (a hormone that induces osteoclast differentiation). No
      TRAP-positive MNCs appeared in the absence of these hormones. Like authentic
      osteoclasts, the TRAP-positive MNCs formed in response to IGF-I and -II bound
      [125I]salmon calcitonin. When mouse bone marrow cells were cultured on ivory
      slices in the presence of either IGF-I or IGF-II for 10 days, numerous resorption
      lacunae were formed. beta-Galactosidase had no effect on IGF-mediated osteoclast
      formation. These results are strong evidence that both IGF-I and IGF-II stimulate
      bone resorption in vitro by enhancing osteoclast formation and function. Our data
      also suggest that the IGFs act through the intermediary of osteoblastic cells to
      stimulate osteoclast activity and that the type I, but not the type II, IGF
      receptor is involved in their responses. We propose that the local production of
      IGF-I and IGF-II may modulate both osteoblast-osteoclast interactions and
      osteoclast formation and play an important role in bone remodeling.

PMID- 7828522
TI  - Regulation of gonadotropin, thyrotropin subunit, and prolactin messenger
      ribonucleic acid expression by pulsatile or continuous protein kinase-C
      stimulation.
AB  - The present study investigated the importance of pulsatile vs. continuous protein
      kinase-C (PKC) stimulation in regulating pituitary gene expression. Adult female
      rat pituitaries were dissociated, and cells were plated for 48 h, then inserted
      into perifusion chambers (n = 5-8/group). Chambers received pulses of GnRH (100
      pM) plus TRH (4 nM) or sn-1,2-dioctanoylglycerol (DOG; peak chamber
      concentration, 0.2, 1, or 5 mM; vehicle pulses to controls) every 60 min or a
      continuous infusion of phorbol 12-myristate 13-acetate (PMA; 20 nM). Secretory
      responses were determined in perifusate fractions collected after 2 and 22 h of
      perifusion. After 24 h of treatment, the cells were recovered, total RNA was
      extracted, and messenger RNAs (mRNAs) were measured by dot blot hybridization.
      The data revealed that GnRH plus TRH and both pulsatile (DOG) and continuous
      (PMA) PKC stimulation increased LH, FSH, TSH, and PRL secretory activity. Pulses
      of GnRH plus TRH increased PRL, alpha, TSH beta, and FSH beta mRNAs, but not LH
      beta mRNA. Pulsatile DOG only increased LH beta and PRL mRNAs, with maximal
      responses seen after the 1-mM dose for LH beta and the 0.2-mM dose for PRL. In
      contrast, PMA stimulated significant increases in alpha, LH beta, and TSH beta,
      but not PRL or FSH beta. These data show that alpha, TSH beta, LH beta, and PRL
      mRNA expression are regulated by PKC. Maximal increases are seen after continuous
      stimulation (via PMA), with the exception of PRL, which requires a pulsatile
      signal pattern. Thus, intermittent activation of PKC does not appear to play a
      major role in regulating pituitary gene expression.

PMID- 7828523
TI  - Endothelin-induced interleukin-6 production by rat aortic endothelial cells.
AB  - Endothelin (ET) produced by endothelial cells has recently been found to be a
      potent vasoconstricting hormone. In this paper, ET isopeptides, both ET-1 and ET
      3, were shown to be potent stimulators of interleukin (IL)-6 production by a rat
      aortic endothelial cell clone, WAE-1. Semi-quantitative polymerase chain reaction
      analysis indicated that augmentation of IL-6 production is due to an increase in
      IL-6 messenger RNA level. Ligand binding assay indicated that most of the
      [125I]ET-1 binding sites correspond to ET receptor type A (ETAR). However, ET
      receptor type B (ETBR) was shown to be also present on this cell line by reverse
      transcription polymerase chain reaction using ETBR-specific primers and by ligand
      binding assay using [125I]ET-3, although the protein receptor level is much lower
      than that of ETAR. ET-1, but not ET-3, induced inositol 1,4,5-triphosphate
      production and an increase in intracellular Ca2+ concentration with similar dose
      response. These data suggest that ET-1 stimulates IL-6 production through ETAR
      phospholipase C activation axis, whereas ET-3 stimulates IL-6 production through
      different signaling pathway. The results shown in this paper raise the
      possibility that ET plays a role in inducing inflammation in endothelium.

PMID- 7828524
TI  - Homologous desensitization of gonadotropin-releasing hormone (GnRH)-stimulated
      luteinizing hormone secretion in vitro occurs within the duration of an
      endogenous GnRH pulse.
AB  - A pulsatile GnRH signal is required for the maintenance of LH and FSH secretion.
      Studies in animals and in perifused pituitary cells have shown that continuous
      exposure to GnRH leads to decreased gonadotropin secretion and a blunted
      secretory response to subsequent pulses of GnRH, a process referred to as
      homologous desensitization. In the current study, we demonstrate that the
      duration of continuous GnRH exposure required to desensitize the gonadotrope in
      vitro is less than the durations of most in vivo GnRH pulses. Perifused male rat
      pituitary cells were tested with 20-sec pulses of 100 nM GnRH at 5-min intervals
      before, immediately upon termination of, and after GnRH infusions of varying
      concentration and duration. Desensitization in response to a GnRH infusion was
      calculated as the decrease in the LH response to the pulse of GnRH immediately
      after the infusion (Dsn pulse) compared to the mean LH response to GnRH pulses
      before and after the infusion. Gonadotropes were completely desensitized after a
      2-min infusion of 10 nM GnRH (P < 0.05), the shortest duration tested. Endogenous
      GnRH pulses, by contrast, average more than 5 min in length. When the duration of
      GnRH infusion was held constant at 4 min, a concentration response for GnRH
      induced desensitization was observed. Gonadotropes were desensitized by GnRH
      concentrations as low as 1 nM (P < 0.05), and maximal desensitization was
      observed with 5 nM GnRH. To determine the recovery period for GnRH-induced
      desensitization, a second series of experiments was performed. Experiments were
      conducted as described above, except the cells were perifused with medium that
      did not contain GnRH (recovery) for varying periods between the GnRH infusion and
      the Dsn pulse. A small response (16% of control) to the Dsn pulse of GnRH was
      observed after 1 min of recovery, and the response was not different from the
      control value (P > 0.05) after a 3-min recovery period. This recovery period is
      consistent with the ability to respond to endogenous GnRH pulses, which rarely
      exceed two per h. We conclude that GnRH-induced secretory desensitization and
      recovery occur within endogenous GnRH pulse durations and interpulse intervals,
      respectively. These data raise the possibility that homologous desensitization
      occurs under some in vivo conditions, providing an unexpected mechanism for
      physiological regulation of gonadotropin secretion.

PMID- 7828525
TI  - Lesions of the iodomelatonin-binding sites of the mediobasal hypothalamus spare
      the lactotropic, but block the gonadotropic response of male Syrian hamsters to
      short photoperiod and to melatonin.
AB  - The aim of this study was to determine whether the iodomelatonin-binding sites
      identified within the preoptic area (POA) or mediobasal hypothalamus (MBH) are
      essential for the photoperiodic control of seasonal reproduction in male Syrian
      hamsters. Animals received sham or bilateral electrolytic lesions directed toward
      either the POA (POA-X; n = 11) or MBH (MBH-X; n = 12) and were then maintained on
      long days (16 h of light and 8 h of darkness) for at least 4 weeks before
      transfer to a short photoperiod (SD; 8 h of light and 16 h of darkness). The
      transscrotal width of the left testis and serum testosterone (Exp 1), PRL, and LH
      (Exp 2) levels were recorded every 4 weeks in lesioned and intact hamsters to
      monitor their reproductive state. Lesions of the MBH, but not the POA, abolished
      the SD-induced gonadal responses (transscrotal width of the left testis after 12
      weeks of SD: MBH-X, 10.0 +/- 0.2 mm; sham, 4.6 +/- 0.1 mm; POA-X, 4.0 +/- 0.1 mm;
      sham, 4.1 +/- 0.1 mm). Similarly, the decrease in serum LH concentrations was
      prevented by lesions of the MBH (serum LH after 12 weeks SD: MBH-X, 0.74 +/- 0.2
      ng/ml; sham, 0.25 +/- 0.1 ng/ml). However, neither lesion prevented the SD
      induced decline in serum PRL (serum PRL after 12 weeks SD: MBH-X, 4.7 +/- 1.0
      ng/ml; sham, 3.1 +/- 0.1 ng/ml; POA-X, 2.0 +/- 0.1 ng/ml; sham, 2.0 +/- 0.1
      ng/ml). To exclude the possibility that the lesion to the MBH prevented gonadal
      regression through disruption of nocturnal melatonin production, MBH-X animals
      were switched to a long day photoperiod, pinealectomized, and fitted with a sc
      cannula for the infusion of either melatonin (500 ng/10 h) or saline (50
      microliters/h) once daily for 6 weeks. A group of neurally intact,
      pinealectomized control animals that received the same infusions showed the
      expected gonadal regression with melatonin treatment, whereas those receiving
      saline vehicle had large testes (melatonin, 0.5 +/- 0.1 g; saline, 3.3 +/- 0.3 g.
      Furthermore, after 6 weeks of infusions, serum LH and PRL concentrations in
      intact melatonin-infused hamsters were significantly reduced (LH: melatonin, 0.2
      +/- 0.04 ng/ml; saline, 1.3 +/- 0.1 ng/ml; PRL: melatonin, 2.2 +/- 0.2 ng/ml;
      saline, 16.9 +/- 3.1 ng/ml). In contrast to the intact controls, none of the MBH
      X animals infused with melatonin exhibited gonadal regression (MBH-X: melatonin,
      2.8 +/- 0.5 g; saline, 2.9 +/- 0.5 g).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7828526
TI  - Induction of uterine activity with oxytocin in late pregnant rats replicates the
      expression of c-fos in neuroendocrine and brain stem neurons as seen during
      parturition.
AB  - We investigated whether delivery could be induced with pulsatile oxytocin and
      whether such treatment activated neurons in the supraoptic nucleus (SON) and
      putative afferent neurons in the nucleus tractus solitarii and ventrolateral
      medulla, as seen during spontaneous parturition. Rats were implanted with a
      jugular venous cannula 1 day before the expected term and on the next morning
      were given a pulse of oxytocin or saline every 10 min for 4 h. Pulses of 10 and
      20 mU oxytocin induced delivery in 77% (14 of 18) of rats, whereas none of the
      control animals (0 of 9) gave birth during the treatment. Lower doses of oxytocin
      were not effective at this time in inducing delivery. Animals were killed either
      before (prepartum groups) or during (parturient groups) delivery, and the brains
      were processed for immunocytochemistry. Oxytocin treatment induced Fos expression
      in SON and brain stem neurons in both parturient rats and rats in which
      parturition was not induced. Fos expression in all sites was significantly higher
      than that in control prepartum rats, but was similar in extent and distribution
      to that in spontaneous parturient rats. In the brain stem, a substantial
      proportion of Fos-immunoreactive cells contained tyrosine hydroxylase-like
      immunoreactivity, and the number of these cells was increased in response to
      oxytocin treatment. As only very few Fos-immunoreactive nuclei in either the SON
      or the nucleus tractus solitarii were observed in virgin rats injected with
      oxytocin, we suggest that intermittent oxytocin injections in late pregnant rats
      induce strong uterine activity, which can stimulate magnocellular and putative
      afferent neurons even before the expulsion of pups.

PMID- 7828527
TI  - The proliferation of normal human breast tissue implanted into athymic nude mice
      is stimulated by estrogen but not progesterone.
AB  - In order to resolve the question of which ovarian steroid stimulates normal human
      mammary epithelial cell proliferation, we have implanted pieces of normal human
      breast tissue subcutaneously into athymic nude mice. These mice were then treated
      with slow-release pellets containing estradiol (E2) or progesterone (P) such that
      serum levels of E2 and P were increased to those seen in normal women. The
      proliferative activity of the tissue implants was assessed by uptake of tritiated
      thymidine and steroid receptor expression was measured immunocytochemically.
      Insertion of a 2 mg E2 pellet 14 days after tissue implantation increased the
      thymidine labeling index (TLI) from a median of 0.4% (n = 34) to a median of 2.1%
      after 7 days (n = 43; P < 0.001 by Mann Whitney U test). In contrast, treatment
      with a P pellet (4 mg) had no effect upon the TLI whereas P (4 mg) in combination
      with E2 (2 mg) had no effect over and above that of E2 alone. There was a
      significant correlation between the increase in TLI and either the E2 content of
      the pellets (P < 0.001 by linear regression) or the serum E2 levels achieved (P <
      0.001). Expression of the P receptor was increased 15- to 20-fold by E2
      treatment. We conclude that E2 is sufficient to stimulate human breast epithelial
      cell proliferation at physiologically relevant concentrations and that P does not
      affect proliferation either alone or after E2 priming.

PMID- 7828528
TI  - Gonadotropin-releasing hormone receptor messenger ribonucleic acid expression in
      rat ovary.
AB  - Rat GnRH pituitary receptor complementary DNA was used to isolate a truncated
      clone from a rat corpus luteum complementary DNA library that proved to be
      identical in sequence to the rat anterior pituitary GnRH receptor. The
      distribution of the GnRH receptor messenger RNA (mRNA) was then determined in rat
      ovary using in situ hybridization. GnRH receptor expression was investigated in
      cyclic female rats and in hypophysectomized immature female rats treated with
      either recombinant human FSH or human menopausal gonadotropin. The expression of
      LH receptor mRNA was determined in serial sections as an index of the health and
      differentiation of the follicles. In cyclic animals, GnRH receptor mRNA was
      detected in granulosa cells at varying stages of follicular development and in
      the corpus luteum. Ovaries from hypophysectomized animals expressed GnRH receptor
      mRNA in the granulosa cells of most follicles. The administration of FSH or human
      menopausal gonadotropin to hypophysectomized animals altered the distribution of
      GnRH receptor mRNA. During antral development, the signal was most abundant in
      medium-sized follicles not expressing LH receptor mRNA and showing signs of
      follicular atresia. However, healthy preovulatory follicles also expressed GnRH
      receptor mRNA. We conclude that the expression of the GnRH receptor gene in
      granulosa cells is 1) individually regulated for each follicle, 2) persists in
      the corpus luteum, and 3) expressed in atretic follicles.

PMID- 7828529
TI  - A comparison of the esterification of steroids by rat lecithin:cholesterol
      acyltransferase and acyl coenzyme A:cholesterol acyltransferase.
AB  - Although fatty acid esters of several steroids have been found in both blood and
      tissues, their biosynthetic origins are uncertain. For example, the fatty acid
      esters of delta 5-3 beta-hydroxysteroids pregnenolone and dehydroepiandrosterone
      (DHEA) are synthesized in tissues by an acyl coenzyme A:acyltransferase. These
      esters are not secreted, and the circulating esters are formed in blood by
      lecithin:cholesterol acyltransferase (LCAT). Fatty acid esters of corticosterone
      (B) and estradiol (E2) are also present in both blood and tissues, but unlike the
      delta 5-3 beta-hydroxysteroids, their structures are so different from
      cholesterol that it would not necessarily follow that they are esterified by the
      same enzyme. We have examined the esterification of the steroids DHEA, B, and E2
      in blood and tissue, in comparison to the esterification of cholesterol, using as
      a model plasma and hepatic microsomes from the rat. All of the steroids were
      esterified in plasma, but at very different rates: cholesterol > DHEA >> E2 = B.
      The LCAT inhibitor, 5.5'-dithiobis-(2-nitrobenzoic acid), inhibited the
      esterification of all of the substrates. DHEA inhibited the esterification of
      cholesterol, albeit only at high concentration. The fatty acid compositions of
      the cholesterol and DHEA esters were analyzed, and they were found to be
      identical, with arachidonate the predominant ester, greater than 60%. In hepatic
      microsomes, the rate of esterification was different than plasma: cholesterol >
      E2 > or = DHEA >> B. Although B was esterified in both plasma and hepatic
      microsomes, the rate was exceedingly slow in both. The acyl coenzyme
      A:cholesterol acyltransferase inhibitor, N'-(2,4-difluorophenyl)-N-[[4-(2,2
      dimethylpropyl)phenyl]- methyl]-N-heptylurea, blocked the esterification of
      cholesterol almost completely, but surprisingly, it had no effect on the
      esterification of the other steroids. The fatty acid esters of cholesterol, E2,
      and DHEA synthesized in the hepatic microsomes were analyzed. The composition of
      the cholesterol esters from the microsomes was very different than the esters of
      DHEA and E2. These results show that all of the steroids tested are esterified by
      LCAT, and consequently that blood LCAT is the probable source of the circulating
      steroidal esters. Most interesting are the studies of microsomal esterification.
      It has been presumed that similar to blood, the esterification of steroids in
      tissues is carried out by the same enzyme that esterifies cholesterol.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7828530
TI  - Unmasking of neuropeptide-Y inhibitory effects on in vitro gonadotropin secretion
      from pituitaries of metestrous, but not proestrous, rats.
AB  - We have recently demonstrated that GnRH-stimulated gonadotropin secretion is
      augmented by coadministration with neuropeptide-Y (NPY) in anterior pituitaries
      removed in the afternoon from proestrous, but not metestrous, rats. To test the
      hypothesis that these effects of NPY are due to an interaction with progesterone
      (P4), we conducted another cycle stage experiment using NPY, adding an in vitro
      treatment with P4. Pituitaries were taken from rats at 0900 h (before the rise of
      P4 on proestrus) on proestrus or metestrus and were perifused for 8 h, with and
      without GnRH pulses. P4 was given continuously in half of each of the basal or
      GnRH-stimulated perifusions. Pulsatile NPY was administered in half of the basal
      or GnRH-stimulated runs in the presence or absence of P4. P4 alone had a
      stimulatory effect on GnRH-induced LH secretion only on the day of metestrus. P4
      did not confer responsiveness to NPY stimulation on either day. Unexpectedly, NPY
      reversed the P4 augmentation of GnRH-stimulated LH release on metestrus. With
      respect to FSH secretion, NPY or P4 alone had a striking suppressive effect on
      GnRH-stimulated FSH secretion rates from pituitaries of metestrous, but not
      proestrous, donors. These data suggest that the previous endogenous endocrine
      environment may be crucial in determining the divergent and interrelated effects
      of P4 and NPY on gonadotropin secretion. In particular, the metestrous
      environment appears to promote a suppressive role for NPY.

PMID- 7828531
TI  - Reduced expression of a naturally deleted form of human proopiomelanocortin
      complementary deoxyribonucleic acid after transfection into Chinese hamster ovary
      cells.
AB  - POMC is the precursor molecule for a number of hormones, ACTH, MSH, and beta
      endorphin. The human genomic sequence has been elucidated, but to date the
      complete human complementary DNA (cDNA) sequence has not been published. Here we
      report the cloning and expression of human POMC cDNA from the anterior pituitary
      gland. Two forms of POMC cDNA have been identified; one sequence agrees with the
      cDNA sequence predicted from the published genomic sequence, and the second is a
      variant with a 9-base pair deletion (corresponding to the loss of three amino
      acids, Ser-Ser-Gly, between residues 67-73). Both POMC cDNA sequences have been
      expressed in Chinese hamster ovary cells. A significant difference was observed
      between the levels of expression in the cells and the amount secreted into the
      media of the two protein precursor molecules. The expression of the deleted
      variant in the cells was 16.4 +/- 0.9% of the level of normal POMC (P < 0.001),
      and in the media the deleted variant was 22.4 +/- 2.2% of the level of normal
      POMC (P < 0.001).

PMID- 7828532
TI  - GH3 cells transfected with gonadotropin-releasing hormone (GnRH) receptor
      complementary deoxyribonucleic acid release secretogranin-II through a
      constitutive pathway after GnRH analog-regulated synthesis: evidence that
      secretory proteins do not contain a sequence that obligates processing through a
      secretory granule or by regulated secretion.
AB  - GGH3 cells (lactotropic GH3 cells transfected with rat GnRH receptor
      complementary DNA) respond to GnRH agonists with time- and dose-dependent release
      of secretogranin-II (SII), a molecule believed to be a marker of the regulated
      pathway of release and a component of secretory granules. Release requires both
      protein and RNA synthesis and is also stimulated by analogs of the cyclic
      nucleotides. Release, as such, appears to be determined by the availability of
      SII, because this process is constitutive once the molecule is synthesized, and
      intracellular levels are at the same steady state whether the receptor is
      occupied by an agonist or an antagonist or is unoccupied. This synthetic
      requirement is consistent with the lag in time from stimulation to release and
      the inhibitory actions of either cycloheximide or actinomycin-D on secretion as
      well as the morphologic observation that storage granules (i.e. secretory
      granules) are absent in these cells. SII, accordingly, can be released
      constitutively and does not require processing through the so-called regulated
      secretory pathway. These observations suggest, in addition, that proteins
      associated with release through regulated pathways do not have "sorting" domains
      that preclude release via constitutive routes or require processing through
      secretory granules.

PMID- 7828533
TI  - Steroid regulation of growth hormone (GH) receptor and GH-binding protein
      messenger ribonucleic acids in the rat.
AB  - In the rat, the GH receptor (GHR) and the GH-binding protein (GHBP), which arise
      from alternative splicing of the same gene, show a sexually dimorphic and GH
      dependent expression pattern. Multiple alternative 5'-untranslated regions (UTRs)
      are present in GHR and GHBP transcripts in the rat, one of which, GHR1, has
      recently been shown to be liver specific and found at higher levels in females.
      We have measured the hepatic GHR1, GHR, and GHBP transcript levels, by RNase
      protection and solution hybridization assay, in animals with differing hormonal
      status, in which hepatic GHR binding and plasma GHBP have been previously
      assayed. Estradiol (E2) induced GHR1 in males, whereas ovariectomy or the
      antiestrogen tamoxifen reduced GHR1 expression in females. The induction of GHR1
      by E2 was GH dependent, being lower in GH-deficient dwarf rats and absent in
      hypophysectomized rats, paralleling previous measurements of plasma GHBP and
      hepatic GHR binding in these animals. Significant changes in GHR1 could explain
      the trends seen in the same extracts when coding region probes were used. Short
      term adrenalectomy had no effect on GHR and GHBP expression, but dexamethasone
      markedly reduced both protein and messenger RNA (mRNA) levels. Corticosterone
      treatment had no effect alone but reduced the E2-induced increase in GHR1 levels,
      whereas methylprednisolone administered orally reduced hepatic GH binding, plasma
      GHBP, and GHR1 mRNA levels. Thus, 5'-UTRs, encoded by different first exons, are
      involved in the regulation of hepatic GHR and GHBP expression and need to be
      considered when comparing effects of hormonal manipulation on the mRNA
      transcripts and protein products of the GHR gene. Previous studies have found
      discrepancies between levels of protein expression and mRNA transcripts measured
      only with coding region probes. Our results suggest that posttranscriptional
      differences related to 5'-UTR heterogeneity in the GHR gene explain some of these
      discrepancies.

PMID- 7828534
TI  - Evidence for hypothalamic control of the diurnal rhythms in prolactin and
      melatonin in the fetal sheep during late gestation.
AB  - We have investigated the effect of surgical disconnection of the fetal
      hypothalamus and pituitary (HPD) on generation of the daily rhythm in fetal
      plasma melatonin and PRL concentrations under long and short photoperiods. Fetal
      HPD or a sham operation was carried out at around 110 days gestation. Ewes
      carrying either HPD fetal sheep (n = 10) or intact fetal sheep (n = 12) were
      exposed to a long light (LL; 16 h of light and 8 h of darkness) or a short light
      (SL; 8 h of light and 16 h of darkness) regimen for the remainder of gestation.
      All ewes were subjected to a 24-h blood-sampling experiment (13 samples collected
      between 0900-0900 h the following day) between 135-140 days gestation, and fetal
      and maternal plasma melatonin and PRL concentrations were measured using specific
      RIAs. The hormonal data were analyzed using multifactorial analysis of variance
      and cosinor analysis. There was an increase in maternal melatonin concentrations
      during the dark phase in each lighting regimen in ewes carrying HPD or intact
      fetal sheep. In the SL regimen, there was also a significant increase in fetal
      melatonin concentrations during the dark phase in the HPD and intact groups.
      Under LL conditions, however, fetal melatonin concentrations were only
      consistently increased during the dark phase in the intact, not the HPD, group.
      The 24-h mean fetal plasma concentrations of PRL were significantly higher (P <
      0.001) in both intact and HPD fetuses in the LL (intact, 111.0 +/- 22.0 pg/ml;
      HPD, 37.6 +/- 7.3 pg/ml) than in the SL regimen (intact, 37.8 +/- 18.4 pg/ml;
      HPD, 6.7 +/- 4.3 pg/ml). There was also a significant interaction (P < 0.001)
      between the effects of fetal surgical treatment and time of day on fetal PRL
      concentrations. In the intact group, fetal PRL concentrations were significantly
      higher (P < 0.05) at 1300 and 1700 h than between 0300-0700 h in both lighting
      conditions. Cosinor analysis also identified a significant rhythm in 8 of the 12
      fetal PRL profiles in the intact group. In contrast, in the HPD group, there was
      no significant effect of time of day on fetal PRL in either the LL or SL regimen,
      and cosinor analysis only identified a significant rhythm in 2 of the 10 fetal
      PRL profiles in this group. We have, therefore, demonstrated that in the fetal
      sheep, HPD resulted in abolition of the diurnal melatonin rhythm under LL
      conditions and in the loss of the diurnal PRL rhythm under LL and SL
      conditions.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7828535
TI  - Increased accumulation of oxytocin messenger ribonucleic acid in the hypothalamus
      of the female rat: induction by long term estradiol and progesterone
      administration and subsequent progesterone withdrawal.
AB  - To examine a possible role for gonadal steroid hormones in the enhanced
      accumulation of hypothalamic oxytocin (OT) messenger RNA (mRNA) and peptide in
      late pregnancy, we used an established model (22) in which sequential
      administration of estradiol (E2) and progesterone (P) SILASTIC capsules to
      ovariectomized rats is followed by removal of P. Long term and sustained E2
      combined with abrupt P withdrawal mimics the gonadal steroid hormone pattern of
      late gestation in the rat (22). Using this paradigm, we demonstrate that OT mRNA
      is increased in the rat hypothalamus after long term P treatment, but only in the
      presence of E2 and only when P capsules are removed 48 h before killing.
      Furthermore, we show that P replacement in primiparous rats during late pregnancy
      blunts the increase in OT mRNA normally observed at the end of gestation. Our
      results support a role for E2 priming and P withdrawal in the enhanced
      accumulation of OT mRNA in the hypothalamus of the female rat.

PMID- 7828536
TI  - Expression of members of the bcl-2 gene family in the immature rat ovary: equine
      chorionic gonadotropin-mediated inhibition of granulosa cell apoptosis is
      associated with decreased bax and constitutive bcl-2 and bcl-xlong messenger
      ribonucleic acid levels.
AB  - The loss of ovarian follicles through atresia, which accounts for greater than
      99% of postnatal female germ cell depletion, is mediated through apoptotic cell
      death. Although recent data have shown that apoptosis in granulosa cells of
      ovarian follicles can be hormonally manipulated, the molecular mechanisms
      responsible for transducing external signals remain to be elucidated. Herein we
      have characterized changes in the expression of the bcl-2 protooncogene (an
      inhibitor of apoptosis), the bax gene (an inducer of apoptosis), and the bcl-x
      gene (which encodes both bcl-xlong, an inhibitor of apoptosis, and bcl-xshort, an
      inducer of apoptosis) during gonadotropin-stimulated follicular development in
      vivo and during atresia of antral follicles incubated in vitro. Complementary DNA
      fragments corresponding to rat bcl-2, rat bax, and rat bcl-x coding sequences
      were obtained by the reverse transcription-polymerase chain reaction (RT-PCR)
      technique using total RNA prepared from immature rat ovaries. Northern blot
      analysis of steady-state bcl-2, bax, and bcl-x messenger RNA (mRNA) levels in
      total RNA prepared from ovaries of immature rats before and after in vivo priming
      with 10 IU equine CG (eCG) revealed that eCG-induced follicular growth and
      survival were associated with a relatively constitutive level of bcl-2 and bcl-x
      expression but markedly reduced levels of bax mRNA (29 +/- 5% of saline-treated
      control animals). Using the RT-PCR technique coupled with Southern blot
      hybridization analysis to distinguish the long vs. short forms of bcl-x (which
      differ in size by 189 base pairs), it was determined that bcl-xlong was the
      predominant message expressed by granulosa cells of eCG-primed ovaries. The eCG
      mediated decrease in bax expression, coupled with a maintenance of bcl-2 and bcl
      xlong mRNA levels, were associated with a pronounced reduction in the extent of
      granulosa cell apoptosis. In contrast, the induction of apoptosis in a
      homogeneous population of healthy antral follicles by incubation in vitro without
      tropic support was associated with an significant increase in bax mRNA levels to
      220 +/- 10% of those detected in freshly isolated, healthy follicles. Moreover,
      bcl-xlong message levels were significantly reduced in follicles incubated for 24
      h to 69 +/- 4% of those levels detected in freshly isolated, healthy follicles.
      However, no significant change in the level of bcl-2 mRNA was detected.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7828537
TI  - Inhibitors of oxidative stress mimic the ability of follicle-stimulating hormone
      to suppress apoptosis in cultured rat ovarian follicles.
AB  - We have reported that members of the bcl-2 gene family are expressed and
      gonadotropin regulated in ovarian granulosa cells during follicular maturation
      and atresia. Because Bcl-2, a protein that prevents apoptosis in several cell
      types, is reported to function as an antioxidant or free radical scavenger, the
      present studies were designed to investigate if oxidative stress plays a role in
      granulosa cell apoptosis during follicular atresia in the immature rat ovary. In
      the first series of experiments, the role of oxidative stress in the induction of
      granulosa cell apoptosis was directly tested using a defined in vitro follicle
      culture system. Healthy antral follicles obtained from equine CG (eCG)-primed
      immature (27 day old) rats were incubated in serum-free medium for 24 h in the
      absence or presence of FSH (100 ng/ml; a control for inhibiting apoptosis),
      superoxide dismutase (SOD; 10-1000 U/ml), ascorbic acid (0.01-1 mM; a free
      radical scavenger), N-acetyl-L-cysteine (25-100 mM; a free radical scavenger and
      stimulator of endogenous glutathione peroxidase activity), or catalase (10-1000
      U/ml). Granulosa cells within follicles incubated in medium alone exhibited
      extensive apoptosis after 24 h of incubation, and this onset of apoptosis was
      blocked by treatment with FSH (29 +/- 4% of controls; P < 0.001, n = 3).
      Moreover, apoptosis in follicles was also inhibited by treatment with SOD (44 +/-
      4% of controls at 1000 U/ml; P < 0.01, n = 3), ascorbic acid (55 +/- 9% of
      controls at 1 mM; P < 0.05, n = 3), N-acetyl-L-cysteine (24 +/- 7% of controls at
      100 mM; P < 0.001, n = 3), or catalase (35 +/- 6% of controls at 1000 U/ml; P <
      0.001, n = 3). In the second series of experiments, complementary DNAs
      corresponding to secreted (SEC-SOD), copper/zinc-containing (Cu/Zn-SOD), and
      manganese-containing (Mn-SOD) forms of rat SOD, rat seleno-cysteine glutathione
      peroxidase (GSHPx), and rat catalase were isolated and used to synthesize
      antisense RNA probes for Northern and slot blot analysis of changes in SOD,
      GSHPx, and catalase gene expression during follicular maturation. In vivo priming
      of 25-day-old female rats for 2 days with 10 IU eCG, which promoted antral
      follicular growth and survival, increased levels of messenger RNA encoding SEC
      SOD (216 +/- 9% of saline-treated controls, P < 0.05, n = 3) and Mn-SOD (222 +/-
      14% of saline-treated controls, P < 0.05, n = 3) vs. saline-treated
      controls.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7828538
TI  - Temporal and stage-specific effects of recombinant human follicle-stimulating
      hormone on the maintenance of spermatogenesis in gonadotropin-releasing hormone
      antagonist-treated rat.
AB  - Despite considerable attention to the hormonal regulation of spermatogenesis, the
      role of FSH in adult mammals remains controversial. This is mainly due to the
      unavailability until recently of FSH preparations free of contaminating LH and
      discrepant results in various species. Using LH-free recombinant human FSH
      (rhFSH), we sought to determine if FSH is able to maintain spermatogenesis in
      rats in which both LH and FSH, but not other pituitary hormones, are markedly
      suppressed by GnRH-A treatment. Groups of five adult SD rats were given daily sc
      injections of vehicle, Nal-Glu-GnRH-A (1.25 mg/kg BW) or GnRH-A + 10 IU rhFSH for
      up to 4 weeks. In agreement with our previous report, GnRH-A treatment for 1 week
      led to a significant (P < 0.05) reduction in testis weight (26.6%) and in the
      number of specific germ cells involving preleptotene (27.7%) and pachytene
      spermatocytes (36.7%) and step 7 spermatids (30.3%) at stage VII of the
      seminiferous epithelial cycle. The number of advanced spermatids declined by
      44.3%. Concomitant administration of rhFSH for 1 week resulted in a significant
      increase in testicular weight, tubular areas at stage VII-VIII, and in the
      absolute volumes of seminiferous tubules and their lumens compared to GnRH-A
      alone. Most importantly, FSH replacement to GnRH-A-treated rats fully attenuated
      the early (1 week) GnRH-A-induced reduction in germ cell numbers at stage VII as
      well as the number of advanced (steps 17-19) spermatids, and effectively
      prevented GnRH-A-induced reduction in the number of pachytene spermatocytes and
      step 7 spermatids for 2 weeks. In addition, FSH replacement to GnRH-A-treated
      rats was able to increase the number of B spermatogonia available for entry into
      meiosis and maintain the number of preleptotene spermatocytes throughout the
      treatment period. The observed beneficial effects of rhFSH on spermatogenesis in
      GnRH-A-treated rats are most likely not due to the stimulation of the Leydig cell
      function (via paracrine interaction between Sertoli and the Leydig cells),
      because FSH addition to GnRH-A had no discernible effect on intratesticular or
      plasma T levels, accessory organs weight, and the total volume of the Leydig
      cells when compared with GnRH-A alone.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7828539
TI  - Expression of a Trk high affinity nerve growth factor receptor in the human
      prostate.
AB  - Nerve growth factor-beta (NGF beta) and a NGF beta-immunoreactive protein derived
      from human prostatic stromal cell secretory protein (hPS) have been shown to
      stimulate the growth of prostate epithelial cells. An NGF beta-immunoreactive
      protein has been localized to the stroma of human prostate tissues, and a low
      affinity NGF receptor (gp75NGFR) has been localized to the adjacent epithelia,
      consistent with the paracrine regulation of prostate growth. Interestingly,
      gp75NGFR is progressively lost during neoplastic progression of the human
      prostate. In this report we have characterized the expression of the signal
      transducing component of the NGF receptor, the Trk tyrosine receptor kinase, in
      prostate epithelial cells that bind exogenous NGF beta and an endogenous NGF beta
      immunoreactive protein in hPS. In this context, a pan-Trk antibody that
      recognizes all of the members of the Trk receptor family (TrkA, TrkB, and TrkC)
      specifically localized expression of the Trk receptor to the epithelial component
      of normal prostate tissue, benign prostatic hyperplasia, and adenocarcinoma
      tissue. The binding of [125I]NGF beta to the surface of primary cultures of human
      prostate epithelia and the TSU-pr1 human metastatic prostate tumor cell line was
      displaced with either excess cold NGF beta or hPS, whereas binding was not
      displaced by epidermal growth factor or platelet-derived growth factor. Scatchard
      plot analysis of [125I]NGF beta binding to these cells identified a low affinity
      binding site (Kd = 1.9 x 10(-9) M) and a high affinity binding site (Kd = 1.8 x
      10(-11) M) on the primary prostate epithelia, whereas only a high affinity
      binding site (Kd = 1.3 x 10(-11) M) was observed on the TSU-pr1 tumor cells.
      Stimulation of TSU-pr1 cells with either NGF beta or hPS induced tyrosine
      phosphorylation of Trk proteins, whereas no phosphorylation was evident in
      untreated cells, cells treated with hPS immunoprecipitated with anti-NGF beta
      antibody, or brain-derived neurotrophic factor- and neurotrophin-3-treated cells.
      The Trk protein was also observed in these cells by immunoblot analysis with pan
      Trk antibody. These results demonstrate a functional Trk receptor in the
      epithelia of the human prostate that is responsive to exogenous NGF beta and an
      endogenous NGF beta-immunoreactive protein in hPS, thereby supporting the concept
      of the paracrine regulation of growth in the human prostate via a stromal
      neurotrophin-epithelial Trk receptor interaction.

PMID- 7828540
TI  - Characterization of an up-stream thyroid transcription factor-1-binding site in
      the thyrotropin receptor promoter.
AB  - A thyroid transcription factor-1 (TTF-1)-binding element in the rat TSH receptor
      (TSHR) promoter, between -189 and -175 basepairs (bp), is important for both
      thyroid-specific expression and thyroid-specific TSH/cAMP autoregulation of the
      TSHR. The identification of an up-stream TTF-1-binding site and its relationship
      to the function of the down-stream TTF-1 element are the subjects of this report.
      Sequence analysis identifies a potential TTF-1 site at -878 bp; deoxyribonuclease
      I footprinting shows that the -881 to -866 bp region is protected by recombinant
      TTF-1 protein and by nuclear extracts from FRTL-5 thyroid cells that contain TTF
      1, but not by extracts from nonfunctioning FRT thyroid or Buffalo rat liver (BRL)
      cells, which have no TTF-1, or by Pax-8. FRTL-5, but not FRT or BRL cell nuclear
      extracts, form a specific protein-DNA complex with this region in gel mobility
      shift analyses; its formation is prevented by TTF-1-binding elements from the
      thyroglobulin promoter. The upstream TTF-1 site acts as an enhancer when coupled
      to a heterologous simian virus-40 promoter-chloramphenicol acetyltransferase
      (CAT) chimera and transfected into FRTL-5 thyroid cells. There is a greater
      increase, 3-vs. 2-fold (P < 0.05), when TSHR promoter-CAT chimeras, which contain
      the up-stream TTF-1 element, pTRCAT5'-907 or pTRCAT5'-886, as opposed to those in
      which it is deleted, pTRCAT5'-907 delta USTTF-1, are transfected into FRTL-5
      cells or cotransfected with a TTF-1 expression vector into BRL cells, which have
      no endogenous TTF-1. The TTF-1-dependent activity of pTRCAT5'-907 delta USTTF-1
      is the same as that of the minimal promoter, -220 to -39 bp, containing only the
      down-stream TTF-1 site in both cells. Transfection of chimeric TSHR-CAT plasmids
      with the down- and/or up-stream TTF-1 site deleted reveals that the down-stream
      TTF-1 element functions in the absence of the up-stream element, but function of
      the up-stream site requires the down-stream TTF-1 element. Like the down-stream
      TSHR TTF-1-binding site, the up-stream TTF-1 site is different from TTF-1 sites
      in the thyroglobulin and thyroid peroxidase promoter, in that it does not
      interact with Pax-8.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7828541
TI  - Sex differences in and effects of estrogen on oxytocin receptor messenger
      ribonucleic acid expression in the ventromedial hypothalamus.
AB  - In situ hybridization techniques were used in the present study to detect
      hypothalamic expression of the oxytocin receptor (OR) gene. Binding studies have
      localized OR to various brain regions and have detected a high density of
      receptors in the ventromedial hypothalamus (VMH), a documented target of estrogen
      action. This study was designed to compare levels of OR messenger RNA (mRNA) in
      the VMH of male and female rats and to study the effects of estrogen treatment on
      mRNA levels in the VMH of female rats. After cloning a rat OR gene from a genomic
      testes library, a probe was generated for use in in situ hybridization assays to
      evaluate sex differences in OR mRNA expression in the VMH. In addition,
      ovariectomized females were treated with estrogen, and VMH OR mRNA expression was
      compared with that in ovariectomized or intact females. The results of these
      studies showed that male rats expressed higher levels of OR mRNA in the VMH than
      females. Estrogen-treated ovariectomized females exhibited significantly greater
      expression in the VMH than either oil-treated or intact females. These results
      support binding studies that have shown oxytocin binding in the VMH to be
      regulated by gonadal steroids and suggest that estrogen may either directly or
      indirectly regulate transcription of the OR gene.

PMID- 7828542
TI  - Characterization of the mitogen-regulated protein (proliferin) receptor.
AB  - Mitogen-regulated protein (MRP/PLF; also called proliferin) is a member of the
      PRL-GH family expressed by the placenta in mid-gestation. This report describes
      an MRP/PLF receptor in uterine membrane preparations from pregnant mice. Peak
      receptor activity occurred at 11 days of gestation with a dissociation constant
      of 6 x 10(-10) M and maximal binding capacity of 86 fmole MRP/PLF/mg membrane
      protein. PRL, PL-I, and mannose-6-phosphate did not compete for binding, and GH
      competed weakly only at high concentrations. Primary cells cultured from uteri
      taken at days 8-11 of gestation responded to MRP/PLF with increases in DNA
      synthesis. Uterine cells from later stages of gestation did not respond to
      MRP/PLF. This is the first reported evidence of a function mediated by MRP/PLF
      and suggests a role for this protein in maternal-fetal interactions during
      reproduction. Thus, it seems that MRP/PLF is a placentally derived growth factor,
      which stimulates proliferation in the uterus in a developmentally defined period
      to coordinate uterine growth with fetal development.

PMID- 7828543
TI  - Characterization of functional opioid delta receptors in a luteinizing hormone
      releasing hormone-producing neuronal cell line.
AB  - Endogenous opioids participate in the regulation of gonadotropin secretion
      through an influence on the release of the hypothalamic LHRH. However, it is not
      clear whether opioids exert a direct effect on LHRH-producing neurons or
      interfere with other systems able to influence LHRH release. A neuronal LHRH
      producing cell line (GT1) developed recently provides a good model to study the
      mechanisms controlling LHRH release. In the present study, the presence of opioid
      receptors on a subclone of GT1 cells (GT1-1) has been investigated. A specific
      and saturable binding of the 3H-labeled nonselective opioid ligand diprenorphine
      ([3H]DIP) was detected by a receptor binding assay on both intact GT1-1 cells and
      crude membrane preparations obtained from these cells. Analysis of saturation
      curves revealed that [3H]DIP apparently binds to a single class of sites with a
      Kd of 0.2 nM and a binding capacity of 125 fmol/mg protein, corresponding to
      approximately 20,000 sites/cell. Selective displacement of the binding of [3H]DIP
      to GT1-1 cells by [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin, [D-Pen2,D-Pen5]enkephalin
      (DPDPE), and U50488H, which are selective ligands, respectively, for mu-, delta-,
      and kappa-receptors, was also evaluated. Only the specific delta-ligand DPDPE
      produced a significant inhibition of the binding of [3H]DIP. [D-Ala2,N-Me
      Phe4,Gly5-ol]Enkephalin and U50488H were totally ineffective. The inhibitory
      effect of the agonist DPDPE on the binding of [3H]DIP was decreased by the
      presence of sodium ions, a typical characteristic of the binding of agonists to
      opioid receptors. Finally, it has been observed that treatment with
      prostaglandins E1 and E2 produces a dramatic increase in cAMP accumulation in GT1
      1 cells, and DPDPE is highly effective in suppressing this effect. On the basis
      of these results, it is possible to postulate the presence of functional delta
      opioid receptors on GT1-1 cells. By extrapolation, one might suggest that
      endogenous opioids may affect LHRH neurons by two mechanisms: a direct one,
      acting via delta-receptors, and an indirect one, through the activation of
      neurons impinging on the LHRH system, which uses mu-receptors.

PMID- 7828544
TI  - Adult-onset hypothyroidism and the cerebral metabolism of (1,2-13C2) acetate as
      detected by 13C nuclear magnetic resonance.
AB  - The effects of adult-onset hypothyroidism on the metabolic compartmentation of
      the cerebral tricarboxylic acid cycle and the gamma-aminobutyric acid (GABA)
      shunt have been investigated by 13C nuclear magnetic resonance spectroscopy. Rats
      thyroidectomized as adults and age-matched controls were infused in the right
      jugular vein with unlabeled or (1,2-13C2) acetate solutions for 60 min. At the
      end of the infusion, the brains were frozen in situ and perchloric acid extracts
      were prepared and analyzed by 13C nuclear magnetic resonance and reverse-phase
      HPLC. Thyroidectomized animals showed a decrease in the incorporation of 13C from
      (1,2-13C2) acetate in cerebral metabolites and an increase in the concentrations
      of unlabeled glutamate and GABA. Computer-assisted interpretation of the 13C
      multiplets observed for the carbons of glutamate, glutamine, and GABA indicated
      that adult-onset hypothyroidism produced 1) a decrease in the contribution of
      infused (1,2-13C2) acetate to the glial tricarboxylic acid cycle; 2) an increase
      in the contribution of unlabeled acetyl-CoA to the neuronal tricarboxylic acid
      cycle; and 3) impairments in the exchange of glutamate, glutamine, and GABA
      between the neuronal and glial compartments. Despite the fact that the adult
      brain has often been considered metabolically unresponsive to thyroid hormone
      status, present results show metabolic alterations in the neuronal and glial
      compartments that are reversible with substitution therapy.

PMID- 7828545
TI  - Apoptosis of male germ cells, a generalized or a cell type-specific phenomenon?

PMID- 7828546
TI  - One of three CCArGG box/serum response elements of the beta-actin gene is an
      insulin-responsive element.
AB  - The cytoskeletal actins are abundant proteins in mammalian nonmuscle cells. We
      have previously reported that physiological concentrations of insulin induced
      beta-actin transcription in rat H4 hepatoma cells. To define whether one or more
      of the three CCArGG box elements or other elements within the beta-actin gene
      promoter is an insulin response element, we transfected H4 cells with regions of
      the human beta-actin gene promoter fused to the chloramphenicol acetyltransferase
      gene. A 350-basepair DNA fragment was isolated that mediates both insulin and
      serum effects. This fragment contains at least two up-stream elements, a CCAAT
      box and a CCArGG box, and accounts for more than 70% of the basal activity of the
      beta-actin promoter in H4 cells. There was a small, but significant, stimulatory
      effect of insulin over maximal serum induction, suggesting a difference in their
      mechanisms of action. Mutation of the CCAAT box drastically reduced basal
      expression, with no effect on insulin induction. In contrast, a mutation of the
      CCArGG element reduced basal expression and completely abolished insulin
      inducibility. Electrophoretic mobility shift assays suggested that insulin
      regulated the activity, but not the binding, of a factor(s) that associates with
      the CCArGG box. These data demonstrate that in H4 cells, insulin induction of
      beta-actin gene expression was mediated at least in part through one of the three
      beta-actin CCArGG elements.

PMID- 7828547
TI  - Insulin-like growth factor-1 stimulation of cells induces formation of complexes
      containing phosphatidylinositol-3-kinase, guanosine triphosphatase-activating
      protein (GAP), and p62 GAP-associated protein.
AB  - The insulin-like growth factor-1 (IGF-1) receptor is structurally related to the
      insulin receptor and shares common features in receptor signaling. These features
      include receptor autophosphorylation, phosphorylation of insulin receptor
      substrate-1, and activation of Ras and phosphatidylinositol-3-kinase (PI3K).
      Previously, we reported that after insulin treatment of rat HTC cells expressing
      human insulin receptors, a unique insulin receptor signaling complex was formed
      that contained the insulin receptor, the p85 subunit of PI3K, GTPase-activating
      protein (GAP), and p62 GAP-associated protein. In the present study, using wild
      type HTC cells, we investigated whether the activated IGF-1 receptor also forms a
      similar signaling complex. To study the proteins present in IGF-1 receptor
      signaling complexes, we used immunoprecipitation and Western blotting analysis
      with appropriate antibodies. In response to IGF-1, insulin receptor substrate-1
      was tyrosine phosphorylated and formed a complex with the PI3K heterodimer that
      consists of a p85 regulatory subunit and a p110 catalytic subunit. In addition, a
      separate complex was formed, consisting of p85, p62 GAP-associated protein and
      GAP. The p62 in this complex was tyrosine phosphorylated. These studies suggest,
      therefore, that the IGF-1 receptor, like the insulin receptor, induces the
      formation of multiple signaling complexes that most likely mediate the
      proliferative effects of these receptors.

PMID- 7828548
TI  - Regulation of deoxyribonucleic acid synthesis in proliferating and
      differentiating trophoblast cells: involvement of transferrin, transforming
      growth factor-beta, and tyrosine kinases.
AB  - This report investigates the regulation of DNA synthesis in trophoblast stem
      cells and differentiating trophoblast cells. Experiments in this study were
      performed on the Rcho-1 trophoblast cell line, which was established from a
      transplantable rat choriocarcinoma. Rcho-1 trophoblast cells can be manipulated
      to proliferate or differentiate along the trophoblast giant cell pathway. DNA
      synthesis in quiescent trophoblast stem cells (maintained in serum-free medium)
      was stimulated by fetal bovine serum and donor horse serum or transferrin to a
      level approximately 30- and 10-fold above the basal level, respectively.
      Transferrin and horse serum were ineffective at maintaining trophoblast cell
      proliferation. In contrast, serum-starved differentiating trophoblast cells
      synthesize DNA at maximal levels and could not be further stimulated by the
      addition of exogenous factors. Fetal bovine serum-stimulated proliferation was
      effectively inhibited by transforming growth factor-beta 1. Experiments with the
      tyrosine kinase inhibitor genistein implicate tyrosine kinase involvement in the
      regulation of DNA synthesis and proliferation in trophoblast stem cells and DNA
      synthesis in differentiating trophoblast cells. Proliferating and differentiating
      trophoblast cells differ in their levels of tyrosine kinase activities and
      express unique tyrosine-phosphorylated proteins. In summary, DNA synthesis and
      proliferation in trophoblast stem cells are under extrinsic control, whereas DNA
      synthesis in differentiating trophoblast cells is under intrinsic control. Both
      mechanisms require tyrosine kinase activity, but the nature of the tyrosine
      kinase pathways in each process appears to be distinct.

PMID- 7828549
TI  - Regulation of insulin-like growth factor I transcription by prostaglandin E2 in
      osteoblast cells.
AB  - Insulin-like growth factor I (IGF-I) is a widely expressed abundant autocrine and
      paracrine factor that regulates the proliferation and differentiation of a
      variety of cell types. Prostaglandin E2 (PGE2) is a potent stimulator of IGF-I
      synthesis in bone. We examined the regulation of IGF-I synthesis by PGE2 in
      osteoblast-enriched (Ob) cells from fetal rat calvaria. PGE2 treatment of Ob
      cells at 1 microM for 2 h resulted in a 5-fold increase in heterogeneous nuclear
      RNA levels, as measured by a reverse transcriptase-polymerase chain reaction
      assay, suggesting an increase in IGF-I gene transcription. RNase protection
      analysis was used to map the transcriptional start sites in the IGF-I gene that
      are used in Ob cells. Consistent with other extrahepatic tissues, initiation of
      transcription occurs primarily at three sites within the 5'-regions of exon 1 of
      the IGF-I gene. PGE2 treatment did not alter start site usage. The regions
      upstream of these transcriptional start sites were analyzed by transiently
      transfecting Ob cells with putative rat IGF-I promoter sequences ligated to a
      luciferase reporter gene. Constructs containing 1.4 kilobases of the 5'-regions
      regions of exons 1 and 2 had significant promoter activity. PGE2 treatment of
      transfected Ob cells increased luciferase activity 5-fold when a 1.4-kilobase
      exon 1 promoter fragment was tested. This increase in luciferase activity was
      time and dose dependent. Smaller regions of the exon 1 promoter sequence gave
      higher basal activity and were less responsive to PGE2. We conclude that regions
      involved in IGF-I regulation by PGE2 are contained within the IGF-I promoter.

PMID- 7828550
TI  - Localization and regulation of the human very low density
      lipoprotein/apolipoprotein-E receptor: trophoblast expression predicts a role for
      the receptor in placental lipid transport.
AB  - The very low density lipoprotein/apolipoprotein-E receptor (VLDLR) is the newest
      member of the low density lipoprotein receptor (LDLR) family. Very little is
      known about VLDLR localization and regulation. Immunohistochemical analysis of
      human placenta with a specific polyclonal antibody detected VLDLR in
      syncytiotrophoblast and intermediate trophoblast cells. VLDLR transcripts were
      also localized in these cells by in situ hybridization histochemistry. In
      addition, VLDLR messenger RNA (mRNA) was detected in villous core endothelial
      cells and cells appearing to be Hofbauer cells. Northern blot analysis of
      placenta revealed a 2.6-fold increase in VLDLR mRNA at term compared to that in
      the first trimester. The regulation of VLDLR expression was studied in JEG-3 and
      BeWo choriocarcinoma cells, two trophoblast-derived cell lines. Treatment of
      these cells with 8-bromo-cAMP caused a profound suppression of VLDLR message,
      whereas LDLR transcripts were increased. Incubation of JEG-3 cells with 25
      hydroxycholesterol did not lead to sterol negative feedback on VLDLR gene
      expression, unlike LDLR mRNA, which declined markedly. Insulin (200 mg/L) up
      regulated VLDLR message in JEG-3 cells 2-fold, as did the fibrate hypolipidemic
      drug, clofibric acid. We conclude that 1) VLDLR is expressed in human placental
      trophoblast cells in a pattern consistent with a role in placental lipid
      transport; 2) VLDLR expression is high at term relative to that in the first
      trimester; and 3) the trophoblast VLDLR is subject to down-regulation by cAMP and
      up-regulation by insulin and fibrate hypolipidemic drugs.

PMID- 7828551
TI  - A novel glycoprotein in the olfactory and pituitary systems of larval and adult
      lampreys.
AB  - A novel homodimeric glycoprotein was isolated and characterized from the
      pituitaries of adult sea lampreys, Petromyzon marinus, modern representatives of
      the earliest vertebrates. The monomer consists of 121 amino-acid residues in a
      sequence that has no resemblance to any known pituitary hormone. Whereas this
      protein is localized in most cells of the rostral pars distalis of adult
      lampreys, we have chosen to name it, nasohypophysial factor (NHF), because it
      first appears in the olfactory system of developing larval lampreys. Not only may
      NHF be a new pituitary hormone but a useful probe for examining the ontogenetic
      and phylogenetic relationships of the pituitary and olfactory systems in
      vertebrates.

PMID- 7828552
TI  - Distribution of the Kexin family proteases in pancreatic islets: PACE4C is
      specifically expressed in B cells of pancreatic islets.
AB  - The distribution of Kexin family proteases in adult rat pancreatic islets was
      investigated by immunohistochemical means using a series of specific antibodies
      specific for PC1, PC2, PC6, Furin, PACE4A and a recently identified member of the
      Kexin family, PACE4C. PACE4C expression was limited to B cells of the pancreatic
      islets. PC2 was found in A and in some D cells more than in B cells and PC1 was
      evident only in B cells. Furin and PC6 were weakly and evenly expressed in the
      entire islet. PACE4A was hardly found in the islets. These findings indicated
      that individual Kexin family proteases are uniquely distributed in the islets and
      suggested that these proteases share roles in these cells as follows: PC2 is
      involved in the peptide hormone precursor processing in A cells and in D cells,
      and PACE4C, PC1 and PC2 (mainly PACE4C and PC1) are responsible for the
      processing event(s) specific to B cells.

PMID- 7828553
TI  - Adrenocortical pregnenolone binding activity resides with estrogen
      sulfotransferase.
AB  - Cytosol prepared from Chinese hamster ovary (CHO)-K1 cells transfected with
      guinea pig estrogen sulfotransferase (EST) cDNA demonstrated high affinity
      binding activity for pregnenolone as well as 17 beta-estradiol but failed to bind
      dehydroepiandrosterone or testosterone. In contrast, cytosol prepared from
      nontransfected CHO-K1 cells did not demonstrate steroid binding activity.
      Additionally, the binding activity for pregnenolone and 17 beta-estradiol was
      dependent on the presence of the cofactor adenosine-3',5'-diphosphate.
      Pregnenolone and 17 beta-estradiol effectively competed with each other for
      binding. On the other hand, pregnenolone, which was not sulfonated, did not
      inhibit the sulfonation of 17 beta-estradiol by expressed EST.

PMID- 7828554
TI  - Glucose stimulates IGF-I gene expression in C6 glioma cells.
AB  - Glucose stimulates expression of the insulin-like growth factor I (IGF-I) gene in
      cultured C6 glioma cells. This stimulation is specific, as the expression of
      other genes, including those encoding hypoxanthine guanine phosphoribosyl
      transferase (HPRT) and ubiquitin, is not similarly affected by glucose. IGF-I
      gene expression is also stimulated by lactate, suggesting that the stimulatory
      effect is mediated by a product of glycolysis. Additional results indicate that
      the abundance of IGF-I mRNA is considerably higher in stationary confluent cells
      than in log-phase growing cells. This regulation is also specific for IGF-I, as
      HPRT mRNA is regulated in the opposite direction.

PMID- 7828555
TI  - Calcium influx following onset of electrical afterdischarge is not required for
      hormone secretion from neuroendocrine cells of Aplysia.
AB  - The neuroendocrine bag cells are an attractive model system for investigating
      cellular mechanisms mediating the effects of membrane excitability on hormone
      secretion because of the ability to easily monitor their electrical and secretory
      functions simultaneously. We investigated the role of extracellular calcium in
      regulating prolonged release of egg-laying hormone from bag cells following
      stimulation of an electrical afterdischarge. We report that calcium influx is
      required for initiation of the afterdischarge, but is not required for prolonged
      hormone secretion once the afterdischarge has been triggered.

PMID- 7828556
TI  - Sequential processing of insulin by cultured kidney cells.
AB  - It is now well established that in kidney, as in liver, endosomes participate in
      the degradation of insulin. Degradation in this compartment involves the action
      of the insulin-degrading enzyme or a similar enzyme with the formation of large
      intermediate products. The role of lysosomes is less clear, for although earlier
      studies suggested that they are the major or sole site of degradation, this has
      been increasing questioned. More recently, it has been concluded that endosomes,
      at least in liver, are the major site of insulin degradation and that classic
      lysosomes are only involved in the latter stages of degradation if at all. As
      intracellular insulin processing varies among cell types, we set out to examine
      directly the processing of insulin within cultured proximal-like opossum kidney
      cells. By means of analytical subcellular fractionation and reverse phase HPLC
      analysis of products, we established the following sequence of events. After
      internalization, [125I]A14-insulin is partially degraded in endosomes. The formed
      products together with intact insulin, which accounts for most of the radioactive
      material in the endosomes, are then directed to the lysosomal compartment, where
      degradation proceeds rapidly to completion. Bacitracin inhibited degradation in
      both compartments and, although not eliminating insulin trafficking, may impair
      the transfer of insulin from endosomes to lysosomes. This study establishes a
      major role for lysosomes in kidney cell insulin degradation.

PMID- 7828557
TI  - Changes in kininogens and kallikrein in the plasma, brain, and uterus during
      pregnancy in the rat.
AB  - Bradykinin is a potent inducer of uterine smooth muscle contractions in rodents
      and primates. Hence, the purpose of the present study was to characterize the
      various components of the kinin system in the plasma, uterus, hypothalamus, and
      anterior pituitary of the rat during pregnancy to determine whether the kinin
      system is involved in the regulation of uterine contractility during pregnancy.
      To achieve this aim, timed pregnant rats were used, groups of animals (n = 6 per
      group) were killed on days 5, 15, 20, 21, and 22, and measurements of kininogen
      and kallikrein activity were performed on plasma and selected tissues. A
      nonpregnant control group was also used, consisting of a group of 10 randomly
      cycling rats. The results of the study revealed that total kininogen levels in
      the plasma rose during pregnancy (days 15-22) to peak on day 22, the day of
      parturition. This rise was due to increases primarily in T-kininogen compared to
      low mol wt (LMW) kininogen. Total kininogen levels in the hypothalamus were
      undetectable during pregnancy; however, anterior pituitary kininogen levels
      increased markedly from days 15-22. Hypothalamic kallikrein activity was very
      markedly increased from days 5-20 only to drop on days 21 and 22 of pregnancy.
      Uterine total kininogen levels were low from days 5-20 of pregnancy, only to
      undergo a marked elevation on days 21 and 22 (the day of parturition). This
      elevation on day 21 was due to increased T- and LMW kininogen levels. Uterine LMW
      kininogen levels were elevated on day 21, followed by a marked fall on day 22.
      This fall was most likely due to increased bradykinin production from LMW
      kininogen, because uterine kallikrein activity was significantly elevated on days
      21 and 22. The increased production of bradykinin in the uterus on the day of
      parturition could play a significant role in the mechanism responsible for
      activation of uterine contractions during this event.

PMID- 7828558
TI  - Apoptosis in testis germ cells: developmental changes in gonadotropin dependence
      and localization to selective tubule stages.
AB  - Recent studies have demonstrated apoptotic DNA fragmentation in the testis of
      immature rats deprived of gonadotropins. However, the exact cell type undergoing
      apoptosis during testis development and the age differences of gonadotropin
      dependence of testis cell apoptosis are unclear. The present study used gel
      fractionation and in situ methods to quantitate developmental changes of testis
      cell DNA fragmentation and to localize the specific cell type affected in
      developing rats with and without treatment with a GnRH antagonist. Apoptotic DNA
      fragmentation in whole testis was measured in rats between 8-70 days of age. A
      gradual increase (1.8- to 2.0-fold) in testis apoptotic DNA fragmentation was
      seen in rats between 16-28 days of age, compared with 8-day-old animals, followed
      by a decrease in adult animals. To study gonadotropin dependence of testicular
      apoptosis, serum FSH and, to a lesser extent, LH were suppressed by treatment
      with a long-acting GnRH antagonist (azaline-B, 250 micrograms/kg body wt, two
      injections at 2-day intervals). Pretreatment with the GnRH antagonist increased
      apoptotic DNA fragmentation in rats between 16-32 days of age but not in younger
      and adult animals demonstrating an age-related change in gonadotropin dependence.
      To identify the exact testis cell type undergoing apoptosis, in situ analysis of
      DNA fragmentation was performed. In rats at 16-24 days of age, spermatocytes in
      selected tubules were found to have increased DNA fragmentation. In contrast,
      neither Leydig cells nor Sertoli cells were affected. In 32-day-old and adult
      animals, increased DNA fragmentation was seen in early primary spermatocytes of
      some tubules. Treatment with GnRH antagonist increased the number of cells with
      DNA fragmentation as well as percentage of tubules affected. In animals between
      16-32 days of age, meiotic spermatocytes were labeled, whereas early spermatids
      were also labeled in 24- and 32-day-old animals. In adult animals, the level of
      apoptotic DNA fragmentation was not affected by GnRH antagonist treatment.
      However, DNA isolated from specific stages of the seminiferous tubules of adult
      animals showed stage-specific changes of apoptotic DNA fragmentation with 2-fold
      higher levels found in stages I and XII-XIV compared with stage VIII. In situ
      analysis of adult testis demonstrated that spermatocytes were the major cell type
      affected. In conclusion, the present study demonstrated that at least three
      factors determine the onset of apoptosis of the male germ cells: 1) the
      developmental stage of the animal; 2) serum levels of gonadotropins, especially
      FSH; and 3) specific stage of the seminiferous epithelial cycle. The present
      approach provides the basis for future analysis of the role of gonadotropins and
      other factors in the regulation of testis cell degeneration in normal and
      pathological states.

PMID- 7828559
TI  - Lack of correlation of distribution of prolactin (PRL) charge isoforms with
      induction of PRL storage.
AB  - GH4C1 cells, rat pituitary tumor cells, produce PRL, but store little relative to
      normal lactotrophs; treating cells with estradiol, insulin, and epidermal growth
      factor increases both PRL storage and accumulation of dense core granules. Normal
      lactotrophs contain several differently charged forms of PRL. We investigated
      whether inducing PRL storage in GH4C1 cells altered the production of these
      forms. Four forms of PRL that differed by charge were found by immunoblots of two
      dimensional gels of extracts of female rat pituitary glands and of secretory
      granules isolated from the glands. Four forms were also secreted by GH4C1 cells.
      The relative abundance of the four forms in the medium of GH4C1 cells, determined
      by [35S]amino acid incorporation for 24h, was 1.2 +/- 0.58%, 91.3 +/- 1.09%, 6.3
      +/- 0.72%, and 1.2 +/- 0.39% of total PRL (mean +/- SEM), from the most basic to
      the most acidic, respectively. Treatment with 1 nM estradiol, 300 nM insulin, and
      10 nM epidermal growth factor did not significantly change the relative abundance
      of the forms. All four forms also were found in GH4C1 cells after 2 h of
      incubation with [35S]amino acids, although no incorporation of 32PO4 was
      detectable over the same incubation time. We conclude that GH4C1 cells produce
      four forms of PRL that differ by charge, as normal lactotrophs do. The increase
      in storage of PRL caused by insulin, estrogen, and epidermal growth factor does
      not result in or is caused by increased secretion of a specific form.

PMID- 7828560
TI  - Inhibition of human hepatocarcinoma cell proliferation by mammalian and fish
      gonadotropin-releasing hormones.
AB  - This study provides the first demonstration that human hepatocarcinoma-derived
      cell line HepG2 contains GnRH receptors and responds to various molecular forms
      of GnRH in terms of inhibition of proliferation in a time- and dose-related
      manner. In addition, GnRH peptides also significantly inhibited the uptake of
      [3H]thymidine by these cells. The effect of GnRH was specific because GnRH
      antagonists reversed the GnRH-mediated inhibition, and non-GnRH peptides had no
      effect on HepG2 cell proliferation. An important finding is that certain fish
      GnRH molecules such as lamprey GnRH, which has little gonadotropin (LH) release
      activity in mammals, suppress hepatocarcinoma cell proliferation with similar
      potency to a superactive mammalian GnRH analog, [D-Lys6]GnRH. These findings may
      have profound implications in the development of an effective chemotherapy for
      treatment of human liver cancer. An added advantage is that fish GnRH forms will
      likely exert little side effect in terms of human pituitary gonadotropin release,
      gonadal steroidogenesis, and reproductive functions in general.

PMID- 7828561
TI  - Antagonistic role of vitamin D3 and retinoic acid on the differentiation of
      chicken hematopoietic macrophages into osteoclast precursor cells.
AB  - An in vitro culture model of osteoclast differentiation is described which is
      derived from homogeneous populations of chick yolk sac and peripheral blood
      macrophages. In primary cultures, both types of macrophages undergo a
      proliferative phase, become quiescent after reaching high cell densities, then
      aggregate and eventually form large multinucleated giant cells (MNGCs),
      presumably by fusion. These MNGCs can be characterized as premature osteoclasts
      on the basis of several morphological and biochemical criteria, although they do
      not undergo the final differentiation step rendering them competent to resorb
      bone in vitro. Clonal analysis of single cell-derived colonies indicates that all
      macrophages have the potential to differentiate into these osteoclast-like cells
      under these culture conditions. Both retinoic acid and 1,25-dihydroxyvitamin D3
      [1,25-(OH)2D3] modulate macrophage growth, but in an antagonistic manner.
      Although retinoic acid strongly promotes macrophage proliferation and impedes
      MNGC formation, 1,25-(OH)2D3 inhibits proliferation and changes the kinetics of
      MNGC formation. Combination experiments reveal that the proliferative signals
      induced by retinoic acid can override the signal to differentiate induced by 1,25
      (OH)2D3. Our results indicate that even though retinoic acid and vitamin D3 act
      through homologous receptors, they have dramatically opposing effects on
      macrophage differentiation toward osteoclast progenitors.

PMID- 7828562
TI  - Distribution of occupied and unoccupied estrogen receptors in the rat brain:
      effects of physiological gonadal steroid exposure.
AB  - In vitro autoradiographic methods have been developed for selective measurement
      of occupied and unoccupied estrogen receptors (ERs) in brain tissue sections.
      Addition of protamine sulfate traps unoccupied ERs in the tissue sections,
      allowing them to be detected after a short period of incubation with labeled
      estrogen. Occupied ERs are assessed, after washing in buffer without protamine to
      eliminate unoccupied receptor, by incubating the sections for 2 h at 37 C to
      exchange isotopically labeled steroid for the endogenous unlabeled ligand. Total
      ER binding capacity is estimated by summing the values for occupied and
      unoccupied ER. In all brain regions of normal females, ER occupation is low at
      estrus, reflecting the very low levels of circulating estradiol present at this
      stage of the estrous cycle, rising to approximately 50% of binding capacity at
      proestrus. By contrast, in intact males ER occupation varies considerably between
      brain regions, from a high of 55% of binding capacity in the bed nucleus of the
      stria terminalis to a low of 21% in the hypothalamic arcuate nucleus. Gonadectomy
      or treatment of intact males with the aromatase inhibitor 4-hydroxy
      androstenedione greatly reduces or eliminates ER occupation, depending on the
      brain region. In both sexes, changes in levels of endogenous gonadal steroids
      have little effect on total (occupied plus unoccupied) ER concentrations, with
      the exception of the hypothalamic ventromedial nucleus of the female, in which
      total ER concentration declines at estrus. These results are consistent with the
      hypothesis that local aromatization may be the primary determinant of regional ER
      occupation in the brain of the male rat, in contrast to the female, in which high
      levels of ER occupation are found only during the preovulatory estrogen surge.
      Although physiological changes in circulating estradiol and aromatizable androgen
      concentrations induce large changes in ER occupation, they have little effect on
      total ER content in most regions of the brain, suggesting that previous reports
      of changes in ER messenger RNA levels under different conditions of gonadal
      steroid exposure may not be directly reflected in steady state levels of the
      cognate receptor site.

PMID- 7828563
TI  - Biliary tract strictures after orthotopic liver transplantation: diagnosis and
      management.
AB  - Biliary tract complications in 105 patients who had undergone orthotopic liver
      transplantation were reviewed in order to determine their incidence and
      localization. In addition, the possible endoscopic and percutaneous management of
      such complications was evaluated. Signs of cholestasis appeared in 32 of 105
      (30.5%) transplant recipients after a mean of 6.5 months (range 1-19 months), and
      visualization of the biliary system was performed in all. Twenty biliary tract
      complications were observed in these 32 patients (62.5%). There were multiple
      strictures, both intrahepatic and extrahepatic, in 11 grafts. Five of the nine
      extrahepatic strictures were not confined to the site of the bile duct
      anastomosis, and involved the whole common bile duct of the donor liver, while
      the remaining four were confined. The multiple intrahepatic and extrahepatic
      strictures were related either to occlusion of the hepatic artery or to the fact
      that the graft had been in a cold ischemic state for a prolonged time. In
      contrast, multiple strictures and necrosis of the whole extrahepatic bile duct
      were attributed to local ischemia due to the harvesting procedure. Stenoses
      strictly confined to the site of anastomosis were thought to be due to surgical
      technique. Ten extrahepatic bile duct stenoses with considerably impaired bile
      flow were corrected endoscopically (four), percutaneously (three) and by surgery
      (three). In four patients with complications in the whole intrahepatic and
      extrahepatic system, retransplantation was necessary. Biliary tract complications
      in our patients occurred in up to 19% after liver transplantation on long-term
      follow-up. Complications of only the extrahepatic system can be treated
      successfully, whereas complications involving multiple stenoses of the
      intrahepatic bile duct system frequently require retransplantation.

PMID- 7828564
TI  - Improved survival after colorectal cancer in patients complying with a
      postoperative endoscopic surveillance program.
AB  - This study investigates whether compliance with a postoperative surveillance
      program in patients with surgically treated colorectal cancer leads to
      prolongation of life. The clinical course of 212 patients who had undergone
      curative resections for colorectal cancer was monitored for at least five years.
      Eighty-eight patients adhered strictly to a rigid endoscopic surveillance
      program, and 124 did not. Tumor recurrences occurred in 10% of compliant and 14%
      of noncompliant patients. Patients with asymptomatic tumor recurrences survived
      significantly longer (p < 0.05; five-year actuarial survival: 42%) than those who
      were symptomatic (five-year actuarial survival: 8%). The overall survival rate
      was significantly higher (p < 0.0002) in compliant patients (five-year actuarial
      survival: 80%) than in noncompliant patients (five-year actuarial survival: 59%).
      Noncompliance increased the risk of early death by a factor of 2.5 (95% CI = 1.5;
      4.2). It is concluded that postoperative endoscopic surveillance leads to early
      tumor detection, and is associated with an improvement in survival in patients
      with colorectal cancer.

PMID- 7828565
TI  - Endoscopic injection of fibrin glue versus polidocanol in peptic ulcer
      hemorrhage: a pilot study.
AB  - In this prospective, randomized trial, bleeding gastroduodenal ulcers in the
      Forrest I and II stages were treated endoscopically with injection of either
      fibrin glue or polidocanol. After exclusion of four patients for various reasons,
      38 patients were treated with fibrin glue (mean: 5.4 ml) and 41 patients with
      polidocanol (mean: 12.1 ml) with control endoscopies routinely performed on days
      1, 3, and 7 after treatment. The two groups were comparable with regard to age,
      sex, ulcer location and Forrest classification. Recurrent bleeding was observed
      in five cases in the fibrin group and in ten cases in the polidocanol group;
      three and two patients in the fibrin and polidocanol groups, respectively, had to
      undergo surgery. We conclude that fibrin glue injection is an effective method
      for the treatment of bleeding gastroduodenal ulcers.

PMID- 7828566
TI  - The contents of free-text endoscopy reports: an inventory and evaluation by
      peers.
AB  - Insight into the current status of endoscopy reports is needed for a discussion
      on the desirability and feasibility of (more) standardized endoscopy reporting.
      We collected, from ten endoscopists, 181 reports in two diagnostic and two
      indication categories. An inventory was made of the subjects dealt with in the
      reports, such as: indication, premedication, therapy plan, and descriptive
      aspects of ventricular ulcers and lower tract polyps. To assess endoscopists'
      opinions on their reports, 16 randomly selected reports were reviewed by the ten
      endoscopists, using the Delphi method. The reports varied enormously in content
      and detail; 19 of the 28 subjects were not explicitly described in more than 50%
      of the studied reports. Such variation in the contents of reports may decrease
      the quality of care. The large number of topics that endoscopists indicate to be
      missing in their reports (on average 14 topics per report) suggests that more
      detail should be given in endoscopy reports. The current method of reporting
      causes endoscopists to omit information that they consider important. Due to the
      low overall consensus among endoscopists on which specific topics to include
      (eight or more endoscopists agreed on 15% of topics) we conclude that general
      criteria for the contents of reports cannot yet be formulated. However, the fact
      that the endoscopists agreed with more than one-third of the remarks made by
      colleagues opens a perspective towards identifying criteria for the formalization
      of certain report categories.

PMID- 7828567
TI  - Overuse syndromes among endoscopists.
AB  - A survey of 400 gastroenterological endoscopists was carried out to determine
      what kinds of overuse syndromes they suffer from as a result of doing endoscopic
      procedures. The response rate was 72%. Thumb pain, hand pain, elbow pain, low
      back pain, and possibly shoulder pain all appear to be caused by endoscopy to at
      least some extent. Physicians who perform the most procedures tend to have the
      highest risk of developing such problems. Age, sex, practice setting, and hobbies
      did not seem to have an impact on the overuse conditions identified. These
      conditions are most likely due to the equipment and technique of endoscopy.
      Further study is needed to determine the anatomic lesions causing the various
      pain states, so that they can be treated or prevented.

PMID- 7828568
TI  - Health hazards and endoscopy: the known and newly experienced--a personal report.

PMID- 7828569
TI  - Does color vision deficiency in the endoscopist influence the accuracy of
      endoscopic diagnosis? An anonymous study with Dutch gastrointestinal
      endoscopists.
AB  - Colors play a major role in the endoscopic diagnosis of many gastrointestinal
      conditions. Gastrointestinal endoscopists in the Netherlands are predominantly
      male (> 90%), and from population data it is to be expected that approximately 8%
      will have a color vision deficiency. The present study was designed to assess the
      prevalence of color vision deficiencies amongst Dutch gastrointestinal
      endoscopists and to determine whether color vision deficiency affects an
      endoscopist's diagnostic skill. One hundred and thirty-nine gastroenterologists
      and physicians of internal medicine took an F2 color vision test and assessed
      nine videofragments of endoscopies. Color vision deficiencies were detected in 8%
      of Dutch gastrointestinal endoscopists. In one out of the nine video excerpts of
      endoscopies, a statistically significant difference was detected between test
      subjects with and without a color vision deficiency. However, this video excerpt
      showed a green pea, which could not be mistaken for a polyp at polypectomy. The
      study therefore does not show any effect of color vision deficiencies on
      endoscopic skills, nor does it show any deviant prevalence of color vision
      deficiencies amongst Dutch gastrointestinal endoscopists.

PMID- 7828570
TI  - Pseudomonas and endoscopy.

PMID- 7828571
TI  - The cost of doing business: occupational hazards for endoscopists.

PMID- 7828572
TI  - Endoscopic retrieval of a self-expanding stainless steel stent from the common
      bile duct.

PMID- 7828573
TI  - Correlation between splenomegaly and oesophageal varices in patients with liver
      cirrhosis.

PMID- 7828574
TI  - Gastrointestinal bleeding from the papilla of Vater.

PMID- 7828575
TI  - Endoscopic papillotomy in a child with a biliocutaneous fistula.

PMID- 7828576
TI  - Endoscopic image of a splenic artery aneurysm.

PMID- 7828577
TI  - Endoscopic demonstration of colonic involvement by a prosthetic graft.

PMID- 7828578
TI  - Research to reality: a critical review of the validity of various criteria for
      the prevention of occupationally induced low back pain disability.
AB  - Criteria have been suggested to reduce the incidence, or severity of low back
      pain disability. Five underlying theories for such criteria have been identified
      in the literature, and a critical review of the validity of these criteria has
      been carried out. Despite attributions elsewhere, peer-reviewed validation of the
      various criteria range from modest to nil. The need for a validation criterion
      for use in workplace design in order to reduce low back pain disability, or
      severity, is identified and the need for an international protocol to allow cross
      study validation of present and future criteria is suggested.

PMID- 7828579
TI  - Lumbosacral compression in maximal lifting efforts in sagittal plane with varying
      mechanical disadvantage in isometric and isokinetic modes.
AB  - Nine normal male subjects (mean age 28.2 years and mean weight 72.6 kg) performed
      20 standardized maximal effort lifting tasks. They were asked to perform stoop
      and squat lifts at half, three-quarters and full individual horizontal reach
      distances in mid-sagittal plane in isometric and isokinetic modes (fixed velocity
      60 cm/s). Both stoop and squat lifts were initiated at the floor level and
      terminated at the individual's knuckle height keeping the horizontal distance
      constant throughout the lift. The isometric stoop lifts were performed with hip
      at 60 degrees and 90 degrees of flexion with hands at preselected reach
      distances. The isometric squat lifts were performed with knees at 90 degrees and
      135 degrees of flexion with hands at similarly preselected reach distances. The
      force was measured using a Static Dynamic Strength Tester with load cell (SM
      1000). The postures were recorded using a two-dimensional Peak Performance System
      with an event synchronizing unit. The load cell was sampled at 60 Hz and the
      video filming was done at 60 frames per second. The force and postural data were
      fed to a biomechanical model (Cheng and Kumar 1991) to extract external moment
      and lumbosacral compression. The strengths generated in different conditions were
      significantly different (p < 0.01). The strength variation ranged by up to 73%
      whereas the lumbosacral compression varied by only up to 15%. A high level of
      lumbosacral compression was maintained in all conditions.

PMID- 7828580
TI  - Exposure assessment of biomechanical stress in repetitive manual work using
      frequency-weighted filters.
AB  - A quantitative exposure assessment strategy for physical stress associated with
      repetitive manual tasks is proposed using continuous biomechanical data measured
      directly from electrogoniometers or force sensors. This paper describes an
      efficient method for reducing large quantities of biomechanical data into a
      quantifiable metric that accounts for recognized musculoskeletal exposure
      factors, including repetitiveness, postural or forceful exertion stress, and
      duration. A frequency domain approach is used for averaging elemental data
      recorded for repetitive cycles. Parameters for frequency-weighted filters are
      developed using psychophysical data for equivalent discomfort levels resulting
      from repetitive movements of different amplitudes and frequencies. These filters
      enable continuous biomechanical data to be filtered and integrated, resulting in
      a single quantity corresponding to psychophysical response characteristics for
      repetitive motion stress. It is anticipated that a similar approach may be used
      for epidemiological response characteristics. Applications of this theory may
      make it possible for assessing exposure to physical stress in a manner analogous
      to the way in which sound level meters are used for measuring exposure to
      acoustic noise. Repetitive wrist flexion and localized discomfort was used for
      demonstrating the feasibility of this approach. Suitable data reduction
      techniques are necessary for evaluating work methods, job designs, and for
      conducting large scale detailed epidemiological investigations of cumulative
      trauma disorder risk factors. Frequency-weighted filters based on human response
      to physical stress at different frequencies can greatly simplify exposure
      analysis and ultimately may make it possible for quantitative exposure limits to
      be established.

PMID- 7828581
TI  - The vav proto-oncogene is required early in embryogenesis but not for
      hematopoietic development in vitro.
AB  - Previous studies have suggested that the vav protooncogene plays an important
      role in hematopoiesis. To study this further, we have ablated the vav
      protooncogene by homologous recombination in embryonic stem (ES) cells.
      Homozygous vav (-/-) ES clones differentiate normally in culture and generate
      cells of erythroid, myeloid and mast cell lineages. Mice heterozygous for the
      targeted vav allele do not display any obvious abnormalities. However, homozygous
      embryos die very early during development. Crosses of vav (+/-) heterozygous mice
      yield apparently normal vav (-/-) E3.5 embryos but not post-implantation embryos
      (> or = E7.5). Furthermore, homozygous vav (-/-) blastocysts do not hatch in
      vitro. These results indicate that vav is essential for an early developmental
      step(s) that precedes the onset of hematopoiesis. Consistent with the phenotypic
      analysis of vav (-/-) embryos, we have identified Vav immunoreactivity in the
      extra-embryonic trophoblastic cell layer but not in the inner embryonic cell mass
      of E3.5 preimplantation embryos or in the egg cylinder of E6.5 and E7.5 post
      implantation embryos. These results suggest that the vav gene is essential for
      normal trophoblast development and for implantation of the developing embryo.

PMID- 7828582
TI  - NF-E2 and GATA binding motifs are required for the formation of DNase I
      hypersensitive site 4 of the human beta-globin locus control region.
AB  - The beta-like globin genes require the upstream locus control region (LCR) for
      proper expression. The active elements of the LCR coincide with strong erythroid
      specific DNase I-hypersensitive sites (HSs). We have used 5' HS4 as a model to
      study the formation of these HSs. Previously, we identified a 101 bp element that
      is required for the formation of this HS. This element binds six proteins in
      vitro. We now report a mutational analysis of the HS4 HS-forming element (HSFE).
      This analysis indicates that binding sites for the hematopoietic transcription
      factors NF-E2 and GATA-1 are required for the formation of the characteristic
      chromatin structure of the HS following stable transfection into murine
      erythroleukemia cells. Similarly arranged NF-E2 and GATA binding sites are
      present in the other HSs of the human LCR, as well as in the homologous mouse and
      goat sequences and the chicken beta-globin enhancer. A combination of DNase I and
      micrococcal nuclease sensitivity assays indicates that the characteristic
      erythroid-specific hypersensitivity of HS4 to DNase I is the result of tissue
      specific alterations in both nucleosome positioning and tertiary DNA structure.

PMID- 7828583
TI  - Determination of heat-shock transcription factor 2 stoichiometry at looped DNA
      complexes using scanning force microscopy.
AB  - Gene activation frequently requires an array of proteins bound to sites distal to
      the transcription start site. The assembly of these protein-bound sites into
      specialized nucleoprotein complexes is a prerequisite for transcriptional
      activation. Structural analysis of these higher order complexes will provide
      crucial information for understanding the mechanisms of gene activation. We have
      used both electron microscopy and scanning force microscopy to elucidate the
      structure of complexes formed between DNA and heat-shock transcription factor
      (HSF) 2, a human heat-shock transcriptional activator that binds DNA as a trimer.
      Electron microscopy reveals that HSF2 will bring together distant DNA sites to
      create a loop. We show that this association requires only the DNA binding and
      trimerization domains of HSF2. Metal shadowing techniques used for electron
      microscopy obscure details of these nucleoprotein structures. Greatly increased
      resolution was achieved by directly imaging the complexes in the scanning force
      microscope, which reveals that at least two trimers are required for the
      association of HSF2-bound DNA sites.

PMID- 7828584
TI  - An inhibitor domain in c-Fos regulates activation domains containing the HOB1
      motif.
AB  - The c-Fos protein has three activation modules at its C-terminus, two of which
      contain motifs (HOB1 and HOB2) which are also present in the activation domains
      of c-Jun. Here we show the existence of two additional activation modules at the
      N-terminus of c-Fos, one of which contains a second HOB1 motif (HOB1-N). The N
      terminus also contains an inhibitor domain (ID1) which silences HOB1 activity.
      GAL4 fusion experiments showed that ID1 can specifically silence HOB1-containing
      activation domains from c-Fos or c-Jun when linked in cis, but will not affect
      other distinct activation domains. The c-Fos related protein, FosB, also contains
      an inhibitor domain. Mutagenic and deletion analyses identify an inhibitor motif
      (IM1) conserved between c-Fos and FosB, which is required for inhibitor function.
      Mutagenesis of IM1 enhances the ability of c-Fos to activate an AP1 bearing
      promoter. Finally, squelching experiments suggest that c-Fos ID1 binds a limiting
      protein involved in inhibition. These results demonstrate the existence of a new
      class of inhibitor domain within transcriptional activators, which acts in a
      sequence specific manner to inhibit a subset of activation domains.

PMID- 7828585
TI  - Periodic cdc25C transcription is mediated by a novel cell cycle-regulated
      repressor element (CDE).
AB  - We show that the cell cycle-regulated transcription of the TATA-less cdc25C gene
      in late S/G2 is largely mediated by a novel promoter element (CDE) located
      directly 5' to one of the two major transcription initiation sites. Genomic
      dimethylsulfate footprinting experiments, using either synchronized or sorted
      normally cycling cells, show the formation in vivo of a CDE-protein complex in
      both G0 and G1 cells and its dissociation in G2. Mutation of the CDE severely
      impairs cell cycle regulation of the cdc25C promoter and results in high
      expression in G0/G1, indicating that the CDE functions as a cell cycle-regulated
      cis-acting repressor element. Cell cycle regulation is also lost upon removal of
      the enhancer region located immediately upstream of the CDE, but is largely
      restored when this enhancerless minimal cdc25C promoter fragment is linked to the
      constitutive SV40 early enhancer. This indicates that the CDE is dependent on the
      presence of a transcriptional enhancer to effect cell cycle regulation. Our
      observations suggest that the periodic activation of the cdc25C gene in late S/G2
      is brought about, at least in part, by a unique regulatory mechanism involving
      the cell cycle-regulated dissociation of a repressor from the CDE.

PMID- 7828586
TI  - Human RPB5, a subunit shared by eukaryotic nuclear RNA polymerases, binds human
      hepatitis B virus X protein and may play a role in X transactivation.
AB  - The X gene of human hepatitis B virus encodes the polypeptide HBx which
      transactivates viral and host genes through a variety of cis-acting enhancer
      elements present in RNA polymerases I, II and III promoters. To better understand
      the mechanism of X transactivation, we cloned cDNAs of proteins that bind HBx.
      Here we demonstrate that one of these cDNAs is a full-length cDNA of human RPB5,
      a subunit shared by RNA polymerases. The HBx transactivation domain and the
      central region of human RPB5 were necessary for the specific binding of the two
      proteins as shown by: (i) in vitro assays using deletion mutants of fusion
      proteins; (ii) in vivo assays which detect associated proteins by co
      immunoprecipitation of the non-fused proteins from transfected HepG2 cells. Over
      expressed HBx seemed to associate with assembled forms of endogenous human RPB5
      in HBx-transfected cells, since the endogenous RPB5 co-immunoprecipitated with
      HBx. The HBx binding region of human RPB5 by itself stimulated chloramphenicol
      acetyltransferase activities from several different reporters having X-responsive
      element(s). Our results support the idea that the interaction of HBx and human
      RPB5 can facilitate HBx transactivation and that human RPB5 has a domain which
      can communicate with transcriptional regulators.

PMID- 7828587
TI  - The identity of the base following the stop codon determines the efficiency of in
      vivo translational termination in Escherichia coli.
AB  - A statistical analysis of > 2000 Escherichia coli genes suggested that the base
      following the translational stop codon might be an important feature of the
      signal for termination. The strengths of each of 12 possible 'four base stop
      signals' (UAAN, UGAN and UAGN) were tested in an in vivo termination assay that
      measured termination efficiency by its direct competition with frameshifting.
      Termination efficiencies varied significantly depending on both the stop codon
      and the fourth base, ranging from 80 (UAAU) to 7% (UGAC). For both the UAAN and
      UGAN series, the fourth base hierarchy was U > G > A approximately C. UAG stop
      codons, which are used rarely in E. coli, showed efficiencies comparable with
      UAAN and UGAN, but differed in that the hierarchy of the fourth base was G > U
      approximately A > C. The rate of release factor selection varied 30-fold at UGAN
      stop signals, and 10-fold for both the UAAN and UAGN series; it correlated well
      with the frequency with which the different UAAN and UGAN signals are found at
      natural termination sites. The results suggest that the identity of the base
      following the stop codon determines the efficiency of translational termination
      in E. coli. They also provide a rationale for the use of the strong UAAU signal
      in highly expressed genes and for the occurrence of the weaker UGAC signal at
      several recording sites.

PMID- 7828588
TI  - Substrate recognition by human RNase P: identification of small, model substrates
      for the enzyme.
AB  - RNase P from HeLa cells can efficiently cleave tRNA precursor molecules in vitro
      but cannot cleave potential substrates from which the D, anticodon and variable
      loops and stems of the tRNA moiety have all been removed. However, molecules from
      which the latter subdomains have been removed individually do serve as
      substrates. We show here that molecules that contain only a 5' leader sequence,
      the acceptor stem and the T stem and loop of the tRNA domain, and a bulge as
      small as one nucleotide downstream from nucleotide 7 in the tRNA sequence at the
      junction of the two stems, can serve as substrates for human RNase P. The
      identity of the nucleotide in the bulge is important in determining both the
      efficiency of the cleavage and the conformation of the substrate and/or the
      enzyme-substrate complex. We also show that the human enzyme locates the
      appropriate site for cleavage of its substrates in part by 'measuring' the length
      of the helices in the acceptor and T stems in both model and natural substrates.

PMID- 7828589
TI  - Concerted evolution of the tandem array encoding primate U2 snRNA occurs in situ,
      without changing the cytological context of the RNU2 locus.
AB  - In primates, the tandemly repeated genes encoding U2 small nuclear RNA evolve
      concertedly, i.e. the sequence of the U2 repeat unit is essentially homogeneous
      within each species but differs somewhat between species. Using chromosome
      painting and the NGFR gene as an outside marker, we show that the U2 tandem array
      (RNU2) has remained at the same chromosomal locus (equivalent to human 17q21)
      through multiple speciation events over > 35 million years leading to the Old
      World monkey and hominoid lineages. The data suggest that the U2 tandem repeat,
      once established in the primate lineage, contained sequence elements favoring
      perpetuation and concerted evolution of the array in situ, despite a pericentric
      inversion in chimpanzee, a reciprocal translocation in gorilla and a paracentric
      inversion in orang utan. Comparison of the 11 kb U2 repeat unit found in baboon
      and other Old World monkeys with the 6 kb U2 repeat unit in humans and other
      hominids revealed that an ancestral U2 repeat unit was expanded by insertion of a
      5 kb retrovirus bearing 1 kb long terminal repeats (LTRs). Subsequent excision of
      the provirus by homologous recombination between the LTRs generated a 6 kb U2
      repeat unit containing a solo LTR. Remarkably, both junctions between the human
      U2 tandem array and flanking chromosomal DNA at 17q21 fall within the solo LTR
      sequence, suggesting a role for the LTR in the origin or maintenance of the
      primate U2 array.

PMID- 7828590
TI  - In vitro RNA editing-like activity in a mitochondrial extract from Leishmania
      tarentolae.
AB  - A mitochondrial extract from Leishmania tarentolae directs the incorporation of
      uridylate (U) residues within the pre-edited domain of synthetic cytochrome b
      (CYb) and NADH dehydrogenase subunit 7 mRNA. This has several characteristics of
      an in vitro RNA editing activity, but no direct evidence for involvement of guide
      RNAs was obtained. Inhibition by micrococcal nuclease suggests a requirement for
      some type of endogenous RNA. The limitation of internal U-incorporation to the
      pre-edited region in the CYb mRNA and the inhibition by deletion or substitution
      of both mRNA anchor sequences for CYb gRNA-I and -II could be consistent either
      with a gRNA-mediated process or a secondary structure-mediated process. A low
      level of incorporation of [alpha-32P]CTP occurs at the same sites as UTP.
      Internal U-incorporation activity is selectively inhibited by heterologous RNAs,
      suggesting an involvement of low affinity RNA-binding proteins which can be
      competed by the added RNA.

PMID- 7828591
TI  - An ABC transporter in the mitochondrial inner membrane is required for normal
      growth of yeast.
AB  - In an attempt to identify a mitochondrial ATP binding cassette (ABC) transporter,
      we have used the polymerase chain reaction to amplify 10 DNA fragments homologous
      to members of the ABC family from the yeast Saccharomyces cerevisiae. We
      disrupted five of the corresponding genes and found that one of the resulting
      null mutants barely grew on rich medium and failed to grow on minimal medium.
      This gene, termed ATM1, encodes a putative 'half-transporter' of 694 amino acids.
      Atm1p is synthesized with an N-terminal mitochondrial matrix-targeting signal and
      is located in the mitochondrial inner membrane, with its C-terminal ATPase domain
      exposed to the matrix. Cells lacking a functional ATM1 gene have an unstable
      mitochondrial genome and have white mitochondria that completely lack
      cytochromes. Atm1p is the first mitochondrial member of the ABC family to be
      identified and the only eukaryotic ABC transporter that has been shown to be
      necessary for normal cellular growth.

PMID- 7828592
TI  - Molecular cloning, structural analysis and functional expression of the proline
      rich focal adhesion and microfilament-associated protein VASP.
AB  - The vasodilator-stimulated phosphoprotein (VASP), a substrate for cAMP- and cGMP
      dependent protein kinases in vitro and in intact cells, is associated with actin
      filaments, focal adhesions and dynamic membrane regions. VASP, cloned here from
      human HL-60 and canine MDCK cells, is organized into three distinct domains. A
      central proline-rich domain contains a GPPPPP motif as a single copy and as a 3
      fold tandem repeat, as well as three conserved phosphorylation sites for cyclic
      nucleotide-dependent protein kinases. A C-terminal domain contains a repetitive
      mixed-charge cluster which is predicted to form an alpha-helix. The hydrodynamic
      properties of purified human VASP together with the calculated molecular mass of
      cloned VASP suggest that the native protein is a homotetramer with an elongated
      structure. VASP over-expressed in transiently transfected BHK21 cells was
      predominantly detected at stress fibres, at focal adhesions and in F-actin
      containing cell surface protrusions, whereas truncated VASP lacking the C
      terminal domain was no longer concentrated at focal adhesions. These data
      indicate that the C-terminal domain is required for anchoring VASP at focal
      adhesion sites, whereas the central domain is suggested to mediate VASP
      interaction with profilin. Our results provide evidence for the structural basis
      by which VASP, both a target of the cAMP and cGMP signal transduction pathways
      and a component of the actin-based cytoskeleton, including the cytoskeleton
      membrane interface, may be able to exchange signals between these networks.

PMID- 7828593
TI  - Tn552 transposase purification and in vitro activities.
AB  - The Staphylococcus aureus transposon Tn552 encodes a protein (p480) containing
      the 'D,D(35)E' motif common to retroviral integrases and the transposases of a
      number of bacterial elements, including phage Mu, the integron-containing element
      Tn5090, Tn7 and IS3. p480 and a histidine-tagged derivative were overexpressed in
      Escherichia coli and purified by methods involving denaturation and renaturation.
      DNase I footprinting and gel binding assays demonstrated that p480 binds to two
      adjacent, directly repeated 23 bp motifs at each end of Tn552. Although donor
      strand cleavage by p480 was not detected, in vitro conditions were defined for
      strand transfer activity with transposon end fragments having pre-cleaved 3'
      termini. Strand transfer was Mn(2+)-dependent and appeared to join a single left
      or right end fragment to target DNA. The importance of the terminal dinucleotide
      CA-3' was demonstrated by mutation. The in vitro activities of p480 are
      consistent with its proposed function as the Tn552 transposase.

PMID- 7828594
TI  - Gamma-tubulin is required for the structure and function of the microtubule
      organizing centre in Drosophila neuroblasts.
AB  - We report that in Drosophila, gamma-tubulin is required for the structure as well
      as the function of microtubule organizing centres (MTOCs). This conclusion is
      based on the identification and phenotypic characterization of a mutant allele of
      the gamma-tubulin gene located at region 23C of the polytene chromosome map. This
      mutation, which we have called gamma-tub23CPl, is caused by the insertion of a P
      element within the 5' untranslated leader of the gamma-tubulin transcript.
      Northern and Western analysis show that gamma-tub23CPl is either a null or a very
      severe hypomorph as no gamma-tubulin mRNA or protein can be detected in mutant
      individuals. Visualization of DNA, MTOCs and microtubules by confocal laser
      scanning microscopy of cells from individuals homozygous for gamma-tub23CPl
      reveals a series of phenotypic abnormalities. Some of these are similar to those
      observed after disruption of gamma-tubulin function in other organisms, including
      mitotic arrest and a dramatic decrease in the number of microtubules, but, in
      addition, we have observed that mutation in this gene also results in highly
      abnormal MTOCs which show a variety of shapes and sizes which we never observed
      in wild type cells. These results show that gamma-tubulin is required for both
      structural and functional roles in the MTOCs.

PMID- 7828595
TI  - Co-localization of L-type Ca2+ channels and insulin-containing secretory granules
      and its significance for the initiation of exocytosis in mouse pancreatic B
      cells.
AB  - We have monitored L-type Ca2+ channel activity, local cytoplasmic Ca2+
      transients, the distribution of insulin-containing secretory granules and
      exocytosis in individual mouse pancreatic B-cells. Subsequent to the opening of
      the Ca2+ channels, exocytosis is initiated with a latency < 100 ms. The entry of
      Ca2+ that precedes exocytosis is unevenly distributed over the cell and is
      concentrated to the region with the highest density of secretory granules. In
      this region, the cytoplasmic Ca2+ concentration is 5- to 10-fold higher than in
      the remainder of the cell reaching concentrations of several micromolar. Single
      channel recordings confirm that the L-type Ca2+ channels are clustered in the
      part of the cell containing the secretory granules. This arrangement, which is
      obviously reminiscent of the 'active zones' in nerve terminals, can be envisaged
      as being favourable to the B-cell as it ensures that the Ca2+ transient is
      maximal and restricted to the part of the cell where it is required to rapidly
      initiate exocytosis whilst at the same time minimizing the expenditure of
      metabolic energy to subsequently restore the resting Ca2+ concentration.

PMID- 7828596
TI  - The C-terminal 165 amino acids of the plasma membrane Ca(2+)-ATPase confer
      Ca2+/calmodulin sensitivity on the Na+,K(+)-ATPase alpha-subunit.
AB  - The C-terminal 165 amino acids of the rat brain plasma membrane (PM) Ca(2+)
      ATPase II containing the calmodulin binding auto-inhibitory domain was connected
      to the C-terminus of the ouabain sensitive chicken Na+,K(+)-ATPase alpha 1
      subunit. Expression of this chimeric molecule in ouabain resistant mouse L cells
      was assured by the high-affinity binding of [3H]ouabain. In the presence of
      Ca2+/calmodulin, this chimeric molecule exhibited ouabain inhibitable Na+,K(+)
      ATPase activity; the putative chimeric ATPase activity was absent in the absence
      of Ca2+/calmodulin and activated by Ca2+/calmodulin in a dose-dependent manner.
      Furthermore, this chimeric molecule could bind monoclonal IgG 5 specific to the
      chicken Na+,K(+)-ATPase alpha 1 subunit only in the presence of Ca2+/calmodulin,
      suggesting that the epitope for IgG 5 in this chimera is masked in the absence of
      Ca2+/calmodulin and uncovered in their presence. These results propose a direct
      interaction between the calmodulin binding auto-inhibitory domain of the PM
      Ca(2+)-ATPase and the specific regions of the Na+,K(+)-ATPase alpha 1 subunit
      that are structurally homologous to the PM Ca(2+)-ATPase. A comparison of the
      deduced amino acid sequences revealed several possible regions within the
      Na+,K(+)-ATPase that might interact with the auto-inhibitory domain of the PM
      Ca(2+)-ATPase.

PMID- 7828597
TI  - Protein kinase C-mediated phosphorylation of the human multidrug resistance P
      glycoprotein regulates cell volume-activated chloride channels.
AB  - The multidrug resistance P-glycoprotein (P-gp), which transports hydrophobic
      drugs out of cells, is also associated with volume-activated chloride currents.
      It is not yet clear whether P-gp is a channel itself, or whether it is a channel
      regulator. Activation of chloride currents by hypotonicity in cells expressing P
      gp was shown to be regulated by protein kinase C (PKC). HeLa cells exhibited
      volume-activated chloride currents indistinguishable from those obtained in P-gp
      expressing cells except that they were insensitive to PKC. HeLa cells did not
      express detectable P-gp but, following transient transfection with cDNA encoding
      P-gp, the volume-activated channels acquired PKC regulation. PKC regulation was
      abolished when serine/threonine residues in the consensus phosphorylation sites
      of the linker region of P-gp were replaced with alanine. Replacement of these
      residues with glutamate, in order to mimic the charge of the phosphorylated
      protein, also mimicked the effects of PKC on channel activation. These data
      demonstrate that PKC-mediated phosphorylation of P-gp regulates the activity of
      an endogenous chloride channel and thus indicate that P-gp is a channel
      regulator.

PMID- 7828598
TI  - Functional interaction of Nic96p with a core nucleoporin complex consisting of
      Nsp1p, Nup49p and a novel protein Nup57p.
AB  - Nic96p has been isolated previously in a complex together with the nuclear pore
      proteins Nsp1p, Nup49p and a p54 polypeptide. In a genetic screen for Nsp1p
      interacting components, we now find NIC96, as well as a novel gene NUP57 which
      encodes the p54 protein (called Nup57p). Nup57p which is essential for cell
      growth contains GLFG repeats in the N-terminal half and heptad repeats in the C
      terminal half. The domain organization of Nic96p is more complex: N-terminally
      located heptad repeats mediate binding to a trimeric Nsp1p-Nup49p-Nup57p complex,
      but are not required for the formation of this core complex; single amino acid
      substitutions in the central domain yield thermosensitive mutants, which do not
      impair interaction with the Nsp1 complex; the C-terminal domain is neither
      essential nor required for binding to the nucleoporin complex, but strikingly
      mutations in this part cause synthetic lethality with nsp1 and nup57 mutant
      alleles. Since a strain in which the Nic96p heptad repeats were deleted shows,
      similar to nsp1 and nup49 mutants, cytoplasmic mislocalization of a nuclear
      reporter protein, we propose that the interaction of the heterotrimeric Nsp1p
      Nup49p-Nup57p core complex with Nic96p is required for protein transport into the
      nucleus.

PMID- 7828599
TI  - B-cell proliferation and induction of early G1-regulating proteins by Epstein
      Barr virus mutants conditional for EBNA2.
AB  - Infection of primary B-lymphocytes by Epstein-Barr virus (EBV) leads to growth
      transformation of these B-cells in vitro. EBV nuclear antigen 2 (EBNA2), one of
      the first genes expressed after EBV infection of B-cells, is a transcriptional
      activator of viral and cellular genes and is essential for the transforming
      potential of the virus. We generated conditional EBV mutants by expressing EBNA2
      as chimeric fusion protein with the hormone binding domain of the estrogen
      receptor on the genetic background of the virus. Growth transformation of primary
      normal B-cells by mutant virus resulted in estrogen-dependent lymphoblastoid cell
      lines expressing the chimeric EBNA2 protein. In the absence of estrogen about
      half of the cells enter a quiescent non-proliferative state whereas the others
      die by apoptosis. EBNA2 is thus required not only for initiation but also for
      maintenance of transformation. Growth arrest occurred at G1 and G2 stages of the
      cell cycle, indicating that functional EBNA2 is required at different restriction
      points of the cell cycle. Growth arrest is reversible for G1/G0 cells as
      indicated by the sequential accumulation and modification of cell cycle
      regulating proteins. EBV induces the same cell cycle regulating proteins as
      polyclonal stimuli in primary B-cells. These data suggest that EBV is using a
      common pathway for B-cell activation bypassing the requirement for antigen, T
      cell signals and growth factors.

PMID- 7828600
TI  - Hemoglobin switching in man and chicken is mediated by a heteromeric complex
      between the ubiquitous transcription factor CP2 and a developmentally specific
      protein.
AB  - The human stage selector protein (SSP) has been implicated in the developmental
      regulation of the globin genes. Binding of SSP to the stage selector element
      (SSE) in the proximal gamma-globin promoter is integral to the competitive
      silencing of a linked beta-promoter in embryonic/fetal stage erythroleukemia
      (K562) cells. We now report the biochemical purification of SSP from K562 cell
      nuclear extract and demonstrate that the ubiquitously expressed transcription
      factor CP2 is pivotal to, but not sufficient for, SSP binding activity. Although
      addition of anti-CP2 antiserum disrupts the formation of the SSP-SSE complex in
      the electrophoretic mobility shift assay (EMSA), recombinant CP2 fails to bind to
      the SSE. Binding of CP2 to the SSE requires a heterodimeric partner present in
      K562 cells. We have defined the molecular weight of the partner protein as 40-45
      kDa in UV and protein cross-linking experiments. An element analogous to the
      human SSE has previously been demonstrated in the chicken beta A-gene-promoter.
      The effects of this element are dependent on the binding of the chicken stage
      selector protein, NF-E4. Comparative studies between human CP2 and chicken NF-E4
      demonstrate homology between the protein complexes. SSP binds to the chicken SSE
      and formation of this complex is ablated by the addition of anti-CP2 antiserum or
      a monoclonal antibody to NF-E4. Western analysis of partially purified NF-E4
      using anti-CP2 antiserum or the NF-E4 monoclonal antibody both demonstrate a
      dominant band at 66 kDa. Similarly, the NF-E4 antibody recognizes the 66 kDa
      human CP2 protein in Western analysis of the SSP-SSE complex.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7828601
TI  - Salvage mitomycin/5-fluorouracil after platinum-based therapy for women with
      advanced ovarian cancer and related gynecologic malignancies.
AB  - PURPOSE: to determine response rates, survival, and toxicity of a regimen of
      mitomycin-C and 5-fluorouracil in patients previously treated with platinum-based
      combinations for ovarian cancer and related gynecologic malignancies. PATIENTS
      AND METHODS: retrospective chart review of all cases of persistent or recurrent
      ovarian, fallopian tube, and peritoneal carcinoma treated with mitomycin-C 7
      mg/m2 followed by continuous infusion of 5-fluorouracil 600 mg/m2/day over 4
      days. RESULTS: 26 patients were treated after a median of 2 prior platinum-based
      regimens, 22 with ovarian cancer, 3 with peritoneal cancer, and one with
      fallopian tube cancer. Only 2 patients completed 6 or more cycles. 2 patients had
      partial responses (8%); no complete responses were seen. 24 patients died a
      median of 3 months after the initiation of therapy, while 2 patients were alive 4
      and 8 months after beginning therapy. All deaths were attributable to disease,
      not complications of treatment. 8 patients required dose modification or
      treatment delay for toxicity. Nine patients required a total of 11 unscheduled
      admissions. CONCLUSIONS: toxicity attributable to mitomycin-C/5-fluorouracil
      therapy of ovarian cancer is acceptable, but responses are few. More effective
      alternative should be sought.

PMID- 7828602
TI  - Ovarian cancer causing upper and lower urinary tract obstruction.
AB  - BACKGROUND: Cervical cancer is the gynecologic malignancy most commonly
      associated with urinary tract obstruction. Ovarian cancer rarely causes this
      problem, but when it does, the obstruction is due to impedance of flow in the
      pelvic ureters. CASE REPORT: A 34 year old female treated by total abdominal
      hysterectomy with ovarian preservation 9 months earlier for presumed stage IV
      endometriosis and menorrhagia presented with a recurrent pelvic mass along with
      symptoms of bladder outlet obstruction. Intravenous urography and computed
      tomography showed bilateral hydronephrosis and confirmed the bladder outlet
      obstruction. Laparotomy revealed a large pelvic mass, grossly resembling
      endometriosis, obstructing the right ureter and impinging upon the urethrovesical
      junction. Final pathological analysis revealed a mucinous cystadenocarcinoma of
      the ovary. CONCLUSION: Urinary tract obstruction, including both urethrovesical
      junction and ureteral obstruction, may be caused by ovarian cancer.

PMID- 7828603
TI  - Image analysis of the distribution of intraperitoneally administered fluids in
      patients with ovarian cancer.
AB  - Patients are selected for intraperitoneal chemotherapy based on the condition of
      the peritoneal cavity and the volume of residual disease, as determined by second
      look surgery. Several techniques have been described to assess the distribution
      of intraperitoneal fluids. They rely on point, as opposed to area, measurements.
      We performed serial radionuclide scans of 15 patients undergoing intraperitoneal
      chemo for ovarian cancer. Scans were performed following intraperitoneal
      administration of 500-1000 ml of 99Tc-labeled human serum albumin in normal
      saline. Each patient underwent three scans at least 4 weeks apart. Radionuclide
      scans were digitized for computerized analysis. Area in picture elements (pixels)
      and optical density (mass) of the 99Tc-labeled regions were determined and
      analyzed for similarities in the pattern of distribution. Area analysis was used
      to divide the patients into two groups. Group 2 patients (n = 7) had more
      patients with < 0.5 cm of residual disease (P = .051) and no evidence of disease
      (P = 0.1) compared with group 1 patients (n = 8). No differences in overall
      survival were found (P = 0.21). No objective measurement of distribution of
      intraperitoneally administered fluids exists. Computer image analysis may be an
      improvement over static scoring techniques to assess non-invasive imaging
      studies.

PMID- 7828604
TI  - Soluble interleukin-2 receptors and CA 125 in ovarian cancer, a longitudinal and
      cross-sectional study.

PMID- 7828605
TI  - Immunohistochemical detection of p185 product, p21 product, and proliferating
      cell nuclear antigen (PCNA) in formalin-fixed, paraffin-embedded tissues from
      ovarian carcinomas. Preliminary data.
AB  - Immunohistochemical techniques for the detection of oncogene products and the
      assessment of cell kinetics can represent promising investigational tools in
      clinical oncology. In the present paper the immunohistochemical expression of
      p185, p21 and proliferating cell nuclear antigen (PCNA) was retrospectively
      assessed in formalin-fixed, paraffin-embedded tissue samples taken from 28
      primary ovarian carcinomas at first surgery. Positive immunostaining for p185 was
      found in 0% of 6 Stage I and 23% of 22 Stage III-IV tumors. Positive
      immunostaining for p21 was observed in 0% of early and 41% of advanced
      carcinomas; this immunohistochemical finding correlated significantly with
      histologic grade (G3 vs G1-2 = 47% vs 9%, p = 0.042). Elevated PCNA
      immunoreactivity was detected in 33% of Stage I and 50% of Stage III-IV tumors.
      Among the 20 patients with advanced carcinoma who underwent cisplatin or
      carboplatin based chemotherapy followed by second-look laparotomy, the pathologic
      complete response (pCR) rate was 36% for patients with low PCNA expression and 0%
      for those with elevated PCNA expression. A tendency towards a higher pCR rate was
      also found for patients with negative immunostaining for p185 or for p21. The
      prognostic value of the immunohistochemical detection of p185, p21, and PCNA in
      ovarian carcinoma deserves to be further investigated.

PMID- 7828606
TI  - Continent urinary diversion (Gotsadze Pouch) after pelvic exenteration for
      gynaecological malignancies.
AB  - The problem of urinary diversion is of major importance in patients requiring
      pelvic exenteration for advanced gynaecological malignancies. Eight patients
      underwent pelvic exenteration (4-total and 4-anterior) at the Georgian Oncologic
      Centre, 7 of them for recurrent cervical carcinoma after combined treatment and 1
      -for primary advanced cervical carcinoma. The original surgical technique for
      construction of detubalarized ileal reservoir with continent umbilical stoma
      (Gotsadze Pouch) is described. Six patients underwent this type of urinary
      diversion with successful results. Urination is patient-controlled via self
      catheterization every 5 to 6 hours. The results obtained by operation can be
      considered as optimal for their functional and rehabilitational properties.

PMID- 7828607
TI  - Retrospective appraisal of intensity of skin postradiation reactions in breast
      cancer patients treated with telegammatherapy.
AB  - Post irradiation skin reaction in patients treated with telegammatherapy is
      evaluated. Exaggerated reaction was noted in patients older than the mean age of
      the entire group.

PMID- 7828608
TI  - Neoplastic association of leiomyoma, bizarre leiomyoma and leiomyosarcoma uteri.
      Case report.
AB  - Leiomyoma uteri is the commonest mesenchymal neoplasia of this organ.
      Leiomyosarcoma uteri is the most frequent histologic variant of all sarcomatous
      forms. Among these there is bizarre leiomyoma, a borderline lesion with potential
      malignity, whose differential diagnosis is very difficult. This paper reports the
      case of a 44 year old woman who was simultaneously diagnosed with these
      anatomicoclinical lesions. The singularity of this case is represented by the
      coexistence in the same patient of three different lesions that, according to our
      data and those reported in the latest literature, do not seem to be correlated.

PMID- 7828609
TI  - Microinvasive carcinoma of the uterine cervix. Diagnostic and therapeutic
      dilemma.
AB  - Squamous microcarcinomas of the uterine cervix represent a focus of controversy
      regarding a useful clinical definition. The confusion of terminology and numerous
      pathological definitions have led to a great variety of surgical treatments from
      the cone to the radical hysterectomy, with pelvic adenectomy. This report
      analyses retrospectively 133 cases of Stage IA cervical cancers which have been
      followed up for 10-240 months. The purpose of this work is to seek a uniform
      therapeutical approach to cervical microcarcinoma with the review of
      International Literature.

PMID- 7828610
TI  - Risk factors for breast cancer. Case-control study results.
AB  - The great importance of knowing the risk factors for breast pathology in order to
      reveal the risk categories is well known. In many geographical areas breast
      cancer is the most common female neoplasm. Recent Italian statistics point out
      that every year 83 women out of 100,000 develop breast cancer and that its
      incidence is increasing. Every year in Italy 10,000 women die of breast cancer.
      In our retrospective study 146 women suffering from breast cancer, treated in our
      Institute from 1970 to 1993, were enrolled. We excluded 4 patients, surgically
      treated in another Institute and 35 who presented a second or a third
      gynaecological cancer. We considered age, menarche, parity and menopausal age in
      all patients in order to evaluate the association of these risk factors with
      breast cancer development. The average age when neoplasm was first diagnosed was
      53.07 years (between 30-84 years), with a 9.4% incidence in patients under 35
      years old. In 41.1% of the cases, menarche was present under 12 years and in only
      14.1% after 14 years, therefore confirming the reduction of mammary cancer risk
      in women with late menarche. Twenty one point five per cent of the patients were
      nulliparous. In our case series no protective factor seemed to be related with 1
      or 2 pregnancies (43.9%). The menopausal average age was 50.2, with an average
      fertile life period of 37.1 years. Our study also considered the location of the
      primary neoplasia (60.7% in the upper-outer quadrant), the tumor size (3.08 cm
      average diameter) and the histological type (81.3% ductal form).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7828611
TI  - Endometrioid carcinoma in pelvic endometriosis in a postmenopausal woman with
      tamoxifen adjuvant therapy for breast cancer. A case report.
AB  - This concerns a 57 year old woman operated on in 1988 for a left radical
      mastectomy due to ductal breast carcinoma and subsequently treated with
      chemotherapy and Tamoxifen adjuvant. In 1990 a laparo-hystero-oophorectomy was
      carried out due to uterine fibromas. The woman continued taking Tamoxifen. Two
      years later a pelvic regeneration appeared, resulting in endometriosis, site of
      adenomatose hyperplasia and of endometrioid carcinoma GI. This furthermore
      confirms the importance of a gynecological follow-up for all women treated with
      Tamoxifen adjuvant therapy.

PMID- 7828612
TI  - Functional neuroimaging in Alzheimer's disease: how far should we go?

PMID- 7828613
TI  - Assessment of cerebral perfusion with single-photon emission tomography in normal
      subjects and in patients with Alzheimer's disease: effects of region of interest
      selection.
AB  - The shape, size and location of regions of interest (ROIs) show considerable
      variability between single-photon emission tomography (SPET) studies in aging and
      Alzheimer's disease, but the possible influence on study results remains unknown.
      We compared three different ROIs in a SPET study with 60 controls and in 48
      patients with probable Alzheimer's disease diagnosed according to the NINCDS
      ADRDA criteria. Regional cerebral blood flow (rCBF) was assessed with SPET using
      technetium-99m d,l-hexamethylpropylene amine oxime (99mTc-HMPAO), normalized to
      the mean activity in a cerebellar reference slice. The three different ROIs were:
      a multi-slice and a single-slice ROI with reference to the normal brain anatomy
      (using an anatomical atlas), and a rectangular (2 x 4 pixels) ROI in the frontal,
      temporal, temporoparietal and occipital cortices. No differences were observed
      for the means of rCBF values between the single-slice and multi-slice ROI's with
      reference to the normal anatomy, but some variability was present for individual
      comparisons. In contrast, significantly higher mean rCBF values were obtained
      with the single-slice rectangular ROIs in all four regions for both patients and
      controls and considerable variability was shown for individual subjects. After
      analysis with multivariate logistic regression and receiver operator
      characteristic curves, the ability of SPET to discriminate between controls and
      Alzheimer patients was similar in the three methods for mild and moderate
      Alzheimer patients (Global Deterioration Scale = GDS of 3 and 4). However, with
      increasing dementia severity (GDS > 4) the rectangular ROIs showed lower ability
      to discriminate between groups compared to the single-slice and multi-slice
      anatomically defined ROIs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7828614
TI  - HMPAO SPET and FDG PET in Alzheimer's disease and vascular dementia: comparison
      of perfusion and metabolic pattern.
AB  - Positron emission tomography (PET) of 18F-2-fluoro-2-deoxy-D-glucose (FDG) and
      single-photon emission tomography (SPET) of 99mTc-hexamethylpropylene amine oxime
      (HMPAO) were performed under identical resting conditions within 3 h in 20
      patients with probable Alzheimer's disease (AD), 12 patients with vascular
      dementia (VD) and 13 normal persons. In the temporoparietal association cortex
      similar impairment of relative regional cerebral glucose metabolism (rCMRGl) and
      relative HMPAO uptake (rCBF) was found. In addition PET showed hypometabolism in
      the occipital association cortex. The functional pattern was condensed to a ratio
      of regional values of association areas divided by regional values of structures
      that are typically less affected by AD. In normals this ratio was significantly
      related to age for PET metabolic data (r = -0.66, P = 0.01). The ratio was
      significantly lower in AD than in VD and controls for both rCMRGl and rCBF. In AD
      only, the metabolic ratio was related to severity of dementia (r = 0.54, P =
      0.003) and age (r = 0.64, P = 0.003). Metabolic differences between normals and
      AD patients were less obvious in old age. In contrast, there were no significant
      correlations between the perfusion ratio and severity of dementia or age.
      Comparing the metabolic and perfusion ratio by receiver operating characteristic
      curves, PET differentiated AD from normals only marginally better than SPET.
      Differentiation between AD and VD was much better achieved by PET. Our results
      suggest that both PET and SPET can distinguish AD patients from controls, whereas
      for differentiation between AD and VD SPET is of little value.

PMID- 7828615
TI  - Evaluation of single-photon emission tomography imaging of supratentorial brain
      gliomas with technetium-99m sestamibi.
AB  - Single-photon emission tomography (SPET) with technetium-99m sestamibi (MIBI) was
      carried out in 61 adult patients with supratentorial expanding brain lesions.
      Thirty-one patients had pathologically proven malignant glioma. Ten patients had
      pathologically proven low-grade glioma, while another 12 patients had a clinical
      diagnosis of low-grade glioma. The other eight patients had a variety of lesions
      including radiation necrosis (3), abscess (2), ischaemic stroke (2) and primary
      brain lymphoma (1). SPET was performed 15 min after administration of 740-930 MBq
      MIBI and transverse, sagittal and coronal views were reconstructed. Using
      computed tomography or magnetic resonance imaging guidance, a MIBI uptake index
      was computed as the ratio of counts in the lesion to counts in the contralateral
      homologous region. In high-grade gliomas, the MIBI index ranged from 1.9 to 6.6
      (mean 3.6 +/- 1.4) whereas it ranged from 0.8 to 1.7 (1.1 +/- 0.2) in the
      pathologically proven low-grade group (P < 0.01). No significant difference was
      found between the two low-grade groups (1.1 +/- 0.2 vs 1.1 +/- 0.2). No overlap
      was found between high-grade and low-grade glioma index values. Patients with
      suspected radiation necrosis, cerebral abscess or ischaemic stroke did not
      demonstrate high MIBI uptake (0.9-2.2), whereas one patient with brain lymphoma
      did (3.9). This study suggests that MIBI SPET imaging is of value in
      distinguishing low-from high-grade supratentorial gliomas in adults.

PMID- 7828616
TI  - Ictal postictal and interictal single-photon emission tomography in the
      lateralization of temporal lobe epilepsy.
AB  - Single-photon emission tomography (SPET) using radioligands that are fixed on
      first pass through the cerebral circulation shows distinctive and rapidly
      changing blood flow patterns accompanying temporal lobe seizures. We sought to
      determine the optimal time to perform SPET studies for clinical seizure
      lateralization in temporal lobe epilepsy. Interictal, ictal and postictal SPET
      scans of 73 consecutively studied patients with unilateral temporal lobe epilepsy
      were read by three blinded observers to assess the accuracy of lateralization in
      each condition. The blinded observers correctly identified the side of focus in
      97% of ictal studies, 72% of postictal studies and 50% of interictal studies. No
      incorrect scores were made in the ictal studies, whilst 5% of postictal and 12%
      of interictal studies were lateralized to the wrong side. Inter-observer
      agreement was best with the ictal studies. The dramatic perfusion changes of
      ictal SPET provide consistent, reliable and easily interpretable information that
      is superior to that provided by interictal and postictal studies. Injection of
      ligand during seizures is therefore the method of choice for SPET to aid the non
      invasive lateralization of temporal seizure foci.

PMID- 7828617
TI  - A method to quantitate cerebral blood flow using a rotating gamma camera and
      iodine-123 iodoamphetamine with one blood sampling.
AB  - A method has been developed to quantitate regional cerebral blood blow (rCBF)
      using iodine-123-labelled N-isopropyl-p-iodoamphetamine (IMP). This technique
      requires only two single-photon emission tomography (SPET) scans and one blood
      sample. Based on a two-compartment model, radioactivity concentrations in the
      brain for each scan time (early: t(e); delayed: td are described as: [formula:
      see text] respectively, where x denotes the convolution integral; Ca(t), the
      arterial input function; f, rCBF; and Vd, the regional distribution volume of
      IMP. Calculation of the ratio of the above two equations and a "table look-up"
      procedure yield a unique pair of rCBF and Vd for each region of interest (ROI). A
      standard input function has been generated by combining the input functions from
      12 independent studies prior to this work to avoid frequent arterial blood
      sampling, and one blood sample is taken at 10 min following IMP administration
      for calibration of the standard arterial input function. This calibration time
      was determined such that the integration of the first 40 min of the calibrated,
      combined input function agreed best with those from 12 individual input functions
      (the difference was 5.3% on average). This method was applied to eight subjects
      (two normals and six patients with cerebral infarction), and yielded rCBF values
      which agreed well with those obtained by a positron emission tomography H2(15)O
      autoradiography method. This method was also found to provide rCBF values that
      were consistent with those obtained by the non-linear least squares fitting
      technique and those obtained by conventional microsphere model analysis. The
      optimum SPET scan times were found to be 40 and 180 min for the early and delayed
      scans, respectively. These scan times allow the use of a conventional rotating
      gamma camera for clinical purposes. Vd values ranged between 10 and 40 ml/g
      depending on the pathological condition, thereby suggesting the importance of
      measuring Vd for each ROI. In conclusion, optimization of the blood sampling time
      and the scanning time enabled quantitative measurement of rCBF with two SPET
      scans and one blood sample.

PMID- 7828618
TI  - Myocardial metabolic imaging by means of fluorine-18 deoxyglucose/technetium-99m
      sestamibi dual-isotope single-photon emission tomography.
AB  - The detection of preserved glucose uptake in hypoperfused dysfunctional
      myocardium by fluorine-18 deoxyglucose (FDG) positron emission tomography (PET)
      represents the method of choice in myocardial viability diagnostics. As the
      technique is not available for the majority of patients due to cost and the
      limited capacity of the PET centres, it was the aim of the present work to
      develop and test FDG single-photon emission tomography (SPET) with the means of
      conventional nuclear medicine. The perfusion marker sestamibi (MIBI) was used
      together with the metabolic tracer FDG in dual-isotope acquisition. A
      conventional SPET camera was equipped with a 511-keV collimator and designed to
      operate with simultaneous four-channel acquisition. In this way, the scatter of
      18F into the technetium-99m energy window could be taken into account by a novel
      method of scatter correction. Thirty patients with regional wall motion
      abnormalities at rest were investigated. The results of visual wall motion
      analysis by contrast cine-ventriculography in nine segments/heart were compared
      with the results of quantitative scintigraphy. The scintigraphic patterns of MIBI
      and FDG tracer accumulation were defined as normal, matched defects and perfusion
      metabolism mismatches. Spatial resolution of the system was satisfactory, with a
      full width at half maximum (FWHM) of 15.2 mm for 18F and 14.0 mm for 99mTc, as
      measured by planar imaging in air at 5 cm distance from the collimator. Image
      quality allowed interpretation in all 30 patients. 88% of segments without
      relevant wall motion abnormalities presented normal scintigraphic results.
      Seventy-five akinetic segments showed mismatches in 27%, matched defects in 44%
      and normal perfusion in 29%. We conclude that FDG-MIBI dual-isotope SPET is
      technically feasible with the means of conventional nuclear medicine. Thus, the
      method is potentially available for widespread application in patient care and
      may represent an alternative to the 201Tl reinjection technique.

PMID- 7828619
TI  - Reverse redistribution of thallium-201 represents a low-risk finding in
      thrombolysed patients following myocardial infarction.
AB  - The aim of the study was to evaluate the prevalence and clinical significance of
      reverse redistribution on thallium-201 imaging in post-myocardial infarction
      patients who have undergone thrombolytic therapy. Sixty-two patients aged 35-79
      (mean 60) years with proven myocardial infarction who had undergone thrombolysis
      were studied 6 weeks post infarction. Standard stress and 4-h redistribution
      imaging was performed with 201Tl following treadmill exercise. Separate day rest
      injection of 201Tl was given after sublingual nitroglycerine; imaging was
      performed at 1 h. Planar images were acquired in three standard views and
      semiquantitative segmental analysis of the images was performed from the
      unprocessed images. All patients had radionuclide ventriculography for the
      assessment of left ventricular ejection fraction and wall motion abnormality.
      Thirty-three patients also had coronary angiography. 201Tl scintigraphy revealed
      fixed defects in 19 patients, reversible defects in 22, and reverse
      redistribution in 21. Those with reverse redistribution had a significantly
      higher exercise capacity (P < 0.01). Mean (SD) left ventricular ejection fraction
      was 46 (12)% for those with fixed defects, 47 (9)% for those with reversible
      defects and 45 (15)% for patients with reverse redistribution (P = NS). The
      regional wall motion abnormality score was 8 (5), 11.8 (2.2) and 14.2 (6)
      respectively in patients with reverse redistribution, redistribution alone and
      fixed defects. Regions with reverse redistribution revealed less regional wall
      motion abnormality compared to the other two groups (P < 0.01). Fifteen patients
      demonstrated significant 201Tl uptake in the region showing reverse
      redistribution, with rest injection of 201Tl following sublingual nitroglycerine,
      suggesting viable myocardium in that region.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7828620
TI  - Antimyosin scintigraphy in patients with acquired and hereditary muscular
      disorders.
AB  - Scintigraphy with indium-111 labelled antimyosin has an established role in the
      evaluation of cardiac muscle damage. This antibody has been shown to cross-react
      with myosin in skeletal muscle. We therefore studied the usefulness of this
      method for the detection of skeletal muscle lesions in rhabdomyolysis, myositis
      and hereditary muscular dystrophies. All nine patients with rhabdomyolysis had
      focal uptake of antimyosin antibody which correlated with the clinical findings
      of soft tissue damage. However, a number of symptomless lesions were also
      detected by immunoscintigraphy. In rhabdomyolysis the target to non-target uptake
      ratios varied from 1.3 to 7.6. Diffuse uptake of antibody in skeletal muscle was
      observed in all three patients with polymyositis-dermatomyositis and in 12 out of
      13 patients with muscular dystrophies. In myositis the intensity of antibody
      accumulation correlated reasonably well with the magnitude of oedema detected by
      magnetic resonance imaging (MRI). Most patients with Becker type or non-X
      chromosomal muscular dystrophies showed slight or moderate uptake of antibody,
      mainly in the lower extremities. In these patients more antibody accumulated in
      the calves than in the thighs, whereas the findings on MRI were more prominent in
      the thighs than in the calves, presumably because of the better preserved muscle
      bulk in the calves. We conclude that antimyosin scintigraphy can be used for the
      detection of muscle lesions not only in acquired muscle diseases but also in
      hereditary muscular disorders, and that immunoscintigraphy provides information
      on muscle disease activity not obtainable with MRI.

PMID- 7828621
TI  - The value of octreotide scintigraphy in patients with lung cancer.
AB  - We evaluated octreotide scintigraphy in 81 untreated patients who were suspected
      of having bronchial carcinoma. Octreotide scintigraphy visualized the primary
      tumour in all of 40 patients with non-small-cell lung carcinoma (non-SCLC), and
      all of 26 patients with SCLC. In the remaining patients, other bronchial disease
      and metastases from extrapulmonary carcinomas were also visualized. Mediastinal
      lymph node involvement and distant metastases were recognized in 5 of 15 and 1 of
      7 patients with non-SCLC, respectively. In vitro, none of the non-SCLCs were
      shown to bear somatostatin receptors. We postulate that the visualization of non
      SCLC during octreotide scintigraphy is caused by binding of labelled octreotide
      to activated leucocytes or to proliferating neuroendocrine cells around the
      tumours. In patients with SCLC, radiologically suspected lymph node involvement
      was visualized for 21 of 25 sites. Distant metastases, especially to the liver
      and abdomen, were missed for 14 of 20 sites, most probably because no laxatives
      were administered and single photon emission tomography of the abdomen was not
      performed. The failure to recognize liver metastases is most probably due to a
      comparable uptake of radioactivity by the surrounding normal liver tissue. In 15
      of 26 patients, previously unrecognized tumour sites were suggested during
      octreotide scintigraphy, leading to a downstaging of 5 of 14 patients with
      limited disease. Unexpected cerebral metastases were suggested in five patients
      with either limited or extensive disease. In all four of these for whom follow-up
      was available, cerebral metastases became manifest 5-8 months after octreotide
      scintigraphy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7828622
TI  - Serum amylase and tissue polypeptide antigen as biochemical indicators of
      salivary gland injury during iodine-131 therapy.
AB  - The study evaluated the possibility of using serum alpha-amylase and tissue
      polypeptide antigen (TPA) as biochemical markers of radiation injury in the
      salivary gland of patients with thyroid carcinoma treated with iodine-131. The
      results demonstrated that the two molecules increased 1 day after 131I
      administration and returned to near control values on the 3rd day. The increase
      was greater and longer lasting in those patients treated with the higher 131I
      administered activity. However, when the patients were divided into groups based
      on recovery time, which determined patients with different radionuclide
      elimination rates, the increase in the two molecules was greater and more lasting
      in those subjects with a longer period of hospitalization. A comparison with the
      values obtained from patients with tumours of the head and neck treated with
      external radiotherapy demonstrated that after the 1st day of treatment the
      salivary gland received an absorbed dose which, based on alpha-amylase levels,
      ranged between 0.24 and 1.89 Gy and, based on TPA levels, between 0.28 and 2.29
      Gy.

PMID- 7828623
TI  - Dosimetry of intravenously administered oxygen-15 labelled water in man: a model
      based on experimental human data from 21 subjects.
AB  - Models based on uniform distribution of tracer in total body water underestimate
      the absorbed dose from H2(15)O because of the short half-life (2.04 min) of 15O,
      which leads to non-uniform distribution of absorbed dose and also complicates the
      direct measurement of organ retention curves. However, organ absorbed doses can
      be predicted by the present kinetic model based on the convolution technique. The
      measured time course of arterial H2(15)O concentration following intravenous
      administration represents the input function to organs. The impulse response of a
      given organ is its transit time function determined by blood flow and the
      partition of water between tissue and blood. Values of these two parameters were
      taken from the literature. Integrals of the arterial input function and organ
      transit time functions were used to derive integrals of organ retention functions
      (organ residence times). The latter were used with absorbed dose calculation
      software (MIRDOSE-2) to obtain estimates for 24 organs. From the mean values of
      organ absorbed doses, the effective dose equivalent (EDE) and effective dose (ED)
      were calculated. From measurements on 21 subjects, the average value for both EDE
      and ED was calculated to be 1.2 microSv.MBq-1 compared with a value of about 0.5
      microSv.MBq-1 predicted by uniform water distribution models. Based on the human
      data, a method of approximating H2(15)O absorbed dose values from body surface
      area is described.

PMID- 7828624
TI  - Optimized localization of bacterial infections with technetium-99m labelled human
      immunoglobulin after protein charge selection.
AB  - To improve the scintigraphic detection of bacterial infections a protein charge
      purified fraction of polyclonal human immunoglobulin was applied as a
      radiopharmaceutical. This purification was achieved by attaching the
      immunoglobulin to an anion-exchanger column and by obtaining the column-bound
      fraction with buffer. The binding to bacteria in vitro and the target to non
      target ratios of an experimental thigh infection with Staphylococcus aureus or
      Klebsiella pneumoniae in mice were evaluated to compare the purified and the
      unpurified immunoglobulin. The percentage of binding to all gram-positive and
      gram-negative bacteria used in this study was significantly (P < 0.03) higher for
      the purified than for the unpurified immunoglobulin. For the in vivo study, mice
      were infected in the thigh muscle with Staph. aureus or K. pneumoniae. After 18 h
      0.1 mg of technetium-99m labelled polyclonal immunoglobulin or 99mTc-labelled
      protein charge-purified polyclonal human immunoglobulin was administered
      intravenously. At all time intervals the target (infected thighs) to non-target
      (non-infected thighs) ratios for both infections were significantly higher (P <
      0.03) for protein charge-purified polyclonal immunoglobulin than for unpurified
      polyclonal human immunoglobulin. Already within 1 h the infected tissues could be
      detected by the purified immunoglobulin. It is concluded that 99mTc-labelled
      protein charge-purified immunoglobulin localizes both a gram-positive and a gram
      negative thigh infection more intensely and faster than 99mTc-labelled unpurified
      immunoglobulin.

PMID- 7828625
TI  - Platelet labelling with indium-hydroxypyridinone and indium-hydroxypyranone
      complexes.
AB  - In order to identify new compounds which label platelets without affecting their
      function, three classes of metal chelating agents have been compared with oxine
      for their efficiency of indium-113m platelet labelling and for their short- and
      long-term effects on platelet function. The 3-hydroxypyridinones (both 2-ones and
      4-ones) and 3-hydroxypyranones are bidentate chelators of trivalent metal ions
      that are neutrally charged in the metal-complexed form and hence gain access to
      cells readily. The hydroxypyranone ethylmaltol has been compared with the 3
      hydroxypyridin-4-one CP94 and to its structurally related lipophilic analogue
      CP25 as well as with the 3-hydroxypyridin-2-one, CP02. The platelet labelling
      efficiencies with these ligands were between 75% and 95% of that obtained with
      oxine, following a 12-min incubation in saline. The optimal concentration for the
      hydroxypyridin-2-ones and hydroxypyridin-4-ones was approximately 10 microM
      compared with 100 microM for the hydroxypyranone ethylmaltol and 60 microM for
      oxine. Oxine and tropolone were found to produce significant inhibition of
      platelet aggregation to collagen in short-term experiments (10 min) or in longer
      term (18 and 42 h) ex vivo platelet cultures respectively. By contrast,
      ethylmaltol had no such inhibitory effects at either time interval. The
      relatively hydrophilic hydroxypyridin-4-one CP94 showed no inhibitory effects on
      collagen-induced aggregation in short-term studies, unlike the more lipid-soluble
      derivative CP25. These results suggest that ethylmaltol and related pyranones may
      have advantages over oxine and tropolone as indium platelet labelling agents
      where it is important not to damage platelets by the labelling process itself.

PMID- 7828626
TI  - Indium-111 labelled pooled human immunoglobulin imaging to monitor the efficacy
      of specific therapy for Pneumocystis carinii pneumonia.
AB  - Functional imaging is ideally suited to monitoring the effect of specific therapy
      on disease processes. In this pilot study five patients with AIDS and
      Pneumocystis carinii pneumonia (PCP) were imaged with Indium-111 labelled pooled
      human immunoglobulin (111In-HIG) during infection and after therapy for PCP. The
      lung activity of 111In-HIG, measured as a lung/heart ratio, was calculated in a
      study performed during infection with PCP and after therapy. In all five patients
      the lung/heart ratio of 111In-HIG was reduced after treatment. The mean reduction
      in heart/lung ratio was 27% (range 12%-53%). If these results are confirmed by a
      larger study, 111In-HIG will be useful in monitoring the response of PCP to
      therapy in patients with AIDS.

PMID- 7828627
TI  - The continuing important role of radionuclide generator systems for nuclear
      medicine.
AB  - In this review, the continuing importance and status of development of
      radionuclide generator systems for nuclear medicine are discussed. Radioisotope
      costs and availability are two important factors, and both nuclear reactors and
      accelerator facilities are required for production of the parent radioisotopes.
      Radionuclide generator research is currently focused on the development of
      generators which provide radioisotopes for positron emission tomography (PET)
      applications and daughter radioisotopes for various therapeutic applications
      which decay primarily by particle emission. Generator research continues to be
      influenced by developments and requirements of complementary technologies, such
      as the increasing availability of PET. In addition, the availability of a wide
      spectrum of tumor-specific antibodies, fragments, and peptides for
      radioimmunodiagnosis and radioimmunotherapy has stimulated the need for generator
      derived radioisotopes. The advantages of treatment of arthritis of the synovial
      joints with radioactive particles (radiation synovectomy) may be expected to be
      of increasing importance as the elderly population increases, and many of these
      agents are prepared using generator-derived radioisotopes such as yttrium-90 and
      rhenium-188. Therapeutic use of the "in vivo generator" is a new approach, where
      the less radiotoxic parent radioisotope is used to prepare tissue-specific
      therapeutic agents. Following in vivo site localization, decay of the parent
      provides the daughter for therapy at the target site. The principal foundation of
      most diagnostic agents will continue to require technetium-99m from the
      molybdenum-99/technetium-99m ("Moly") generator. With the limited availability of
      nuclear reactors and facilities necessary for production and processing of
      fission 99mTc and the significant issues and problems associated with radioactive
      waste processing, however, the possibility of utilizing lower specific activity
      99Mo produced from neutron activation of enriched 98Mo may become practical in
      the future.

PMID- 7828628
TI  - Undeserved bad press for bone scans: reply.

PMID- 7828629
TI  - Mechanisms of exercise-induced asthma.

PMID- 7828630
TI  - Host defence capacities of pulmonary surfactant: evidence for 'non-surfactant'
      functions of the surfactant system.
AB  - The most well characterized function of pulmonary surfactant is its ability to
      reduce surface tension at the alveolar air-liquid interface, thereby preventing
      lung collapse. However, several lines of evidence suggest that surfactant may
      also have 'non-surfactant' functions: specific components of surfactant (proteins
      and phospholipids) may interact with different alveolar cells, inhaled particles
      and micro-organisms modulating pulmonary host defence systems. SP-A, the most
      abundant surfactant protein, binds to alveolar macrophages via a specific surface
      receptor with high affinity [128]. Such binding effects the release of reactive
      oxygen species from resident alveolar macrophages if SP-A is properly presented
      to the target cell. SP-A also stimulates chemotaxis of alveolar macrophages
      [142], and serves as an opsonin in the phagocytosis of herpes simplex virus [161]
      Candida tropicalis [138] and various bacteria [137]. In addition, SP-A enhances
      the uptake of particles by monocytes and culture-derived macrophages [140] and
      improves bacterial killing. SP-D, another hydrophobic surfactant-associated
      protein, might interact with alveolar macrophages as well, stimulating the
      release of oxygen radicals [148], while for the hydrophilic surfactant proteins
      SP-B and SP-C no macrophage interactions have been described so far. SP-A and SP
      D are members of the so-called 'collectins', pattern recognition molecules
      involved in first line defence. While some surfactant proteins appear to
      stimulate certain macrophage defence functions, surfactant phospholipids seem to
      inhibit those of lymphocytes. Suppressed lymphocyte functions include
      lymphoproliferation in response to mitogens and alloantigens, B cell
      immunoglobulin production and natural killer cell cytotoxicity. Concerning
      surfactant's phospholipid composition phosphatidylglycerol is more suppressive
      than phosphatidylcholine on a molar basis [38]. Bovine surfactant has an
      immunosuppressive effect on the development of hypersensitivity pneumonitis in a
      guinea pig model [150]. Despite these interesting observations, several important
      questions concerning the interactions of surfactant components with pulmonary
      host defence systems remain unanswered. Sufficient host defence in the lungs
      works through various humoral-cellular systems in conjunction with the specific
      anatomy of the airways and the gas exchange surface--how does the surfactant
      system fit into this network? Surfactant and alveolar cells are both altered
      during lung injury--is there a relationship between alveolar cells from RDS
      patients and the endogenous surfactant isolated from such patients? How does
      exogenous surfactant as used for substitution therapy modulate the defence system
      of the host? Some of those artificial surfactants have been shown to inhibit the
      endotoxin-alveolar macrophages, PMNs and monocytes including IL-1, IL-6 and TNF
      [139,152].(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7828631
TI  - Plasma homocysteine in relation to serum cobalamin and blood folate in a
      psychogeriatric population.
AB  - Plasma homocysteine, serum cobalamin and blood folate were analysed in 296
      consecutive patients referred to a psychogeriatric department for diagnosis of
      mental disease. Plasma homocysteine correlated with positive significance with
      age and serum creatinine, and with negative significance with serum cobalamin and
      blood folate. Approximately 35-40% of the patients with low serum cobalamin (<
      150 pmol l-1) or low blood folates (< 150 nmol l-1) exhibited normal values of
      plasma homocysteine (< 19.9 mumol l-1). Possibly, these patients do not have a
      deficiency of the vitamins in the tissue. At least 7.5% of the patients with
      serum cobalamin levels (> 150 pmol l-1) showed an inexplicably increased level of
      plasma homocysteine. These patients might have a deficiency of tissue cobalamin
      despite the normal serum cobalamin levels. The effect of cobalamin
      supplementation for 7-10 days on plasma homocysteine was tested in 62 patients
      with different levels of serum cobalamins. We found the most pronounced decrease
      of plasma homocysteine in the patients with lowest serum cobalamin levels and in
      the patients with highest plasma homocysteine, indicating that the percentage
      decrease of the initial concentration of plasma homocysteine could reflect the
      degree of cobalamin deficiency. Folate supplementation for 7-10 days reduced
      plasma homocysteine not only in patients with folate deficiency but also in those
      with a normal folate status, and even in patients with cobalamin deficiency. The
      latter patients further reduced their plasma homocysteine after additional
      cobalamin treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7828632
TI  - Contribution of glycaemic control, endogenous lipoproteins and cholesteryl ester
      transfer protein to accelerated cholesteryl ester transfer in IDDM.
AB  - In an earlier study we demonstrated that the transfer of cholesteryl ester (CET)
      estimated as the net mass of CE lost from HDL to the apoB-containing lipoproteins
      (VLDL + LDL) during incubation of plasma is accelerated in normolipidaemic
      patients with insulin-dependent diabetes mellitus (IDDM). Recombination
      experiments with isolated lipoprotein fractions employing this same mass transfer
      assay indicated that this disturbance resulted from dysfunction of VLDL and not
      from changes in the activity of CE transfer protein (CETP). In this study, we
      sought first to determine whether CET estimated with an isotopic method that
      measures the transfer of radiolabelled CE from exogenous HDL from non-diabetic
      controls to endogenous VLDL + LDL was also increased in IDDM and, if so, the
      extent to which this disturbance was affected by glycaemic control, VLDL and
      CETP. As observed with the mass transfer assay, the rate of transfer of the HDL
      CE label to VLDL + LDL was also significantly accelerated in IDDM plasma (IDDM: k
      = 0.256 +/- 0.07; control: k = 0.092 +/- 0.05; mean +/- SD; P < 0.001). Fasting
      glucose and fructosamine correlated with both isotopic transfer (k) (r = 0.54, P
      = 0.009; r = 0.57, P = 0.005, respectively) and the mass of CE transferred at 2 h
      (r = 0.55, P = 0.006; r = 0.59, P = 0.004, respectively). Recombination
      experiments revealed that isotopic CET was accelerated when: (a) IDDM VLDL were
      combined with controls HDL and d > 1.21 fractions; and (b) IDDM d > 1.21 plasma
      fractions containing CETP were combined with controls VLDL + LDL and
      HDL.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7828633
TI  - Low levels of essential fatty acids are related to impaired delayed skin
      hypersensitivity in malnourished chronically ill elderly people.
AB  - Essential fatty acid (FA) deficiency, which may accompany protein-energy
      malnutrition (PEM), has been associated with impaired inflammatory reactions. We
      evaluated this relationship by analysing FA profiles and delayed cutaneous
      hypersensitivity in 20 malnourished elderly non-cancer patients and in 20 age
      matched control patients. As indicated by serum cholesterol and serum
      triglycerides, the lipid levels were decreased by about one-third in the subjects
      with PEM. In comparison with the controls, there was a reduction in the omega 3
      FA (e.g. eicosapentanoate) in total serum lipids (mg l-1) and serum phospholipids
      (%) of 40% and 47%, respectively. Reductions in serum omega 6 FA (e.g. linoleate
      and arachidonate) levels corresponded to the drop in total FA concentrations
      (30%). The cutaneous hypersensitivity was impaired in 14 of the malnourished
      patients. The magnitude of the skin reaction was positively correlated (P < 0.05)
      to the concentrations of eicosapentanoate in serum lipids and serum
      phospholipids, as well as to the linoleate concentration in total serum lipids.
      Six of the malnourished patients took part in a nutritional intervention
      programme for 3 months. In parallel with an improvement in the nutritional status
      there was a 35% increase (P < 0.05) in the total omega 3 FA serum concentration.
      Negative skin tests became positive and the median skin induration enlarged
      threefold (P < 0.05). Thus, deficiency of omega 3 FA might be one factor
      contributing to cutaneous anergy in elderly malnourished patients.

PMID- 7828634
TI  - Kinetics of circulating hyaluronan in humans. 4.
AB  - The elimination of intravenously injected hyaluronan (HA) from the blood was
      investigated in 12 healthy volunteers. Three consecutive 30 min infusions of HA
      were given, separated by 90 min washout periods. Blood samples were taken before,
      during and after each infusion and the plasma HA concentration was determined.
      The deposition of HA was modelled according to a Michaelis-Menten kinetic model
      which included natural synthesis of HA. Km and Vmax was estimated to 0.34 +/-
      0.13 microgram ml-1 and 3.48 +/- 0.97 microgram min-1 kg-1 b.w., respectively.
      The endogenous input was calculated to be 24 +/- 11 micrograms min-1 and was
      found to correlate to the age of the subjects (P < 0.05). As the baseline HA
      concentration was 0.031 +/- 0.21 microgram ml-1, the rate of elimination was
      linear in the normal concentration range. The calculated Vd was about 75% higher
      than a weight-estimated plasma volume. The total amount of HA excreted by the
      kidneys during the study period was 394 +/- 77 micrograms, which corresponded to
      approximately 1.7% of the total input of HA into the circulation during the
      experiment.

PMID- 7828635
TI  - Influence of age on cerebral potentials evoked by oesophageal balloon distension
      in humans.
AB  - The recording of viscerosensory cerebral evoked potentials is a new field in the
      research on gastrointestinal perception. The aim of our study was to assess the
      relationships between age and peak amplitudes and latencies of cerebral
      potentials evoked by balloon distension of the human oesophagus. In 16 healthy
      volunteers (aged 21-59 years), cerebral evoked potentials were recorded from a
      midline scalp electrode, using a series of 50 rapid balloon inflations with 13 ml
      of air. Peak to peak amplitudes (N1-P1, P1-N2) and peak latencies (N1, P1, N2)
      were assessed. Inverse correlations were found between age and N1-P1 amplitude (P
      < 0.05), and between age and P1-N2 amplitudes (P < 0.05). N1 and P1 latencies
      were significantly longer in elderly patients (N1: P < 0.05; P1: P < 0.05).
      Amplitudes and peak latencies of cerebral potentials evoked by balloon distension
      of the oesophagus are age-dependent. In cerebral evoked potential studies,
      patients and healthy controls should be age-matched.

PMID- 7828636
TI  - Urodilatin: a new approach for the treatment of therapy-resistant acute renal
      failure after liver transplantation.
AB  - A pilot study was performed in patients after liver transplantation (Ltx) to
      examine the effect of continuous intravenous urodilatin (URO, CDD/ANP-95-126)
      infusion as an alternative therapy of acute renal failure (ARF) resistant to
      conventional therapy. Eight patients who developed ARF after liver
      transplantation and fulfilled requirements for haemodialysis/haemofiltration were
      treated. After URO infusion was started, renal function improved and all patients
      developed a strong diuresis and natriuresis within 2-4 h. The extracellular
      expansion due to sodium and water retention in anuric/oliguric ARF lead to an
      increased central venous pressure (CVP) and elevated blood pressure. During the
      URO infusion CVP declined and systolic, as well as diastolic, blood pressure were
      stable. In six patients where haemodialysis/haemofiltration could be avoided,
      serum creatinine (SC) and blood urea nitrogen (BUN) declined during URO treatment
      and creatinine clearance (CC) also improved significantly. Fluid and electrolyte
      disturbances changed promptly and normalized. This was in concordance with renal
      excretion of electrolytes. Two patients still required
      haemodialysis/haemofiltration. The six patients who did not require
      haemodialysis/haemofiltration after URO treatment normalized concerning their
      renal function and did well in a control period of 12 weeks. The study shows that
      continuous low dose URO infusion may present a new concept for treatment of
      postoperative acute renal failure resistant to conventional therapy.

PMID- 7828637
TI  - Mixed estrogenic and anti-estrogenic activities of yuehchukene--a bis-indole
      alkaloid.
AB  - Anti-estrogenic effects of yuehchukene were observed in rat uterotrophic, mice
      vaginal smear and MCF-7 cell growth assays. Whereas yuehchukene per se was
      estrogenic in these bioassay models, the co-administration of yuehchukene and an
      optimal dose of 3,17 beta-estradiol (estradiol) could attenuate the maximum
      estrogenic response due to estradiol alone. The anti-estrogenic effect of
      yuehchukene in rat uterine hypertrophy was corroborated by a parallel attenuation
      of ornithine decarboxylase activity in these tissues. Yuehchukene binds to rat,
      mice and MCF-7 cell estrogen receptors with a relative binding affinity of 1/150
      to 1/300. This binding affinity was positively related to estrogenicity as
      determined by uterotrophic assay and MCF-7 cell growth. However, this estrogenic
      effect did not correlate with the degree of competitive receptor binding by a
      weaker agonist. Indole-3-carbinol and methylbutadienylindole could induce
      ethoxyresorufin O-deethylase and estradiol-2-hydroxylase in rat liver and MCF-7
      cells. It is postulated that the 'free' indole moiety of yuehchukene could
      possess similar induction activity. Thus yuehchukene may have a dual
      pharmacological function. While the intact molecule is a weak estrogen, the
      'free' indole moiety in yuehchukene may induce an enhancement of estradiol-2
      hydroxylase, thus terminating the biological activity of the endogenous estrogen
      pool. There is obvious benefit in attenuating the estrogen level in post
      menopausal breast cancer patients without going directly to the use of tamoxifen
      or aromatase inhibitor. Yuehchukene may serve this purpose. In this context, the
      pharmacological evaluation of a hydroxylated yuehchukene analogue and the anti
      estrogenic effect of methylbutadienylindole acid-condensation products are now
      being studied in earnest.

PMID- 7828638
TI  - Antianxiety actions of Ca2+ channel antagonists with Vogel-type conflict test in
      rats.
AB  - We examined the effects of various derivatives of Ca2+ channel antagonists in a
      modified rat Vogel-type conflict model. Flunarizine (10 and 20 mg/kg),
      nicardipine (20 mg/kg), and verapamil (20 mg/kg), given as single i.p.
      injections, significantly increased punished lickings by 50-110%. Chronic
      administration of diltiazem, at 20 mg/kg i.p. for 8 days, a dose ineffective with
      a single i.p. injection, produced a significant anticonflict action. The
      possibility that Ca2+ channel antagonists have anxiolytic action should be
      considered.

PMID- 7828639
TI  - d-Fenfluramine and d-norfenfluramine hypophagias do not require increased
      hypothalamic 5-hydroxytryptamine release.
AB  - d-Fenfluramine (2.5 mg/kg i.p.) caused marked hypophagia in food-deprived rats
      and significantly increased medial hypothalamic extracellular 5-hydroxytryptamine
      (5-HT) as indicated by in vivo microdialysis. When the drug was given after the 5
      HT synthesis inhibitor p-chlorophenylalanine (150 mg/kg per day x 3) the
      hypophagic response was unimpaired but dialysate 5-HT concentration no longer
      rose. The d-fenfluramine metabolite d-norfenfluramine (1.5 mg/kg i.p.) caused
      slightly greater hypophagia than the parent drug and completely blocked feeding
      in animals pretreated with p-chlorophenylalanine, but dialysate 5-HT was
      increased in neither circumstance. The results provide evidence against mediation
      of the hypophagic effects of d-fenfluramine and d-norfenfluramine by increased
      availability of 5-HT to receptors.

PMID- 7828640
TI  - Blockade of human IsK channels expressed in Xenopus oocytes by the novel class
      III antiarrhythmic NE-10064.
AB  - cRNA encoding the human IsK protein was injected into Xenopus oocytes and the
      expressed channels were investigated using the two-microelectrode voltage-clamp
      method. The novel class III antiarrhythmic NE-10064 (1-[[[5-(4-chlorophenyl)-2
      furanyl]methylene]-amino]-3- [4-(4-methyl-1-piperazinyl)-butyl]-2,4
      imidazolidinedione dihydrochloride) was tested for its ability to block these
      channels. The compound displayed potent inhibitory effects with an EC50 of 5.4
      microM. The block caused by NE-10064 was use-dependent, i.e. channels had to be
      activated for the inhibition to occur. Further, the reversal of the inhibition
      during the wash-out period was use-dependent. Finally, the blockade of human IsK
      channels by NE-10064 appeared to be voltage-dependent, being more pronounced at
      depolarized potentials. We conclude that this novel class III antiarrhythmic is a
      potent inhibitor of human IsK channels and suggest that such effects could be
      involved in its antiarrhythmic action.

PMID- 7828641
TI  - Dermorphin-induced hyperexcitability in hippocampal CA3 and CA1 in vitro.
AB  - Dermorphin, a specific mu 1-opioid receptor agonist, has been studied for its
      effects on the physiology of the rat hippocampal slice. Population responses in
      CA3 to threshold levels of stimulation from both the Schaffer collaterals and
      mossy fibers were markedly enhanced in the presence of 50-100 nM dermorphin,
      while CA1 responses to threshold Schaffer collateral stimulation were less
      effected. Responses at higher stimulus levels than threshold were negligibly
      responsive to dermorphin, although at 500 nM dermorphin all responses became
      epileptiform and in some slices spontaneous bursting erupted. [L-Ala2]Dermorphin,
      a biologically inactive dermorphin analogue, did not increase response amplitudes
      nor evoke epilepsy in the slice. 5 microM naloxone blocked the effect of
      dermorphin on Schaffer collateral and mossy fiber-evoked responses, though less
      effectively in the latter case. These data provide in vitro evidence to support
      in vivo observations that excessive mu-opioid receptor activation can be
      proconvulsant in the hippocampus, but that normally the receptors may function as
      facilitatory modulators of responses in the threshold range.

PMID- 7828642
TI  - Differing actions of nitropropane analogs of GABA and baclofen in central and
      peripheral preparations.
AB  - In the guinea-pig isolated ileum, both baclofen (5-100 microM) and gamma
      aminobutyric acid (GABA; 5-100 microM) induced a bicuculline-insensitive
      depression of cholinergic twitch contractions which was reversibly and
      competitively antagonised by 3-amino-1-nitropropane (50-250 microM). 3-Amino-1
      nitropropane (pA2 = 5.0 +/- 0.1) was twice as potent as 2-hydroxysaclofen (pA2 =
      4.5 +/- 0.1), but was equipotent with 3-aminopropyl(P-diethoxymethyl)phosphinic
      acid (CGP 35348) (pA2 = 4.9 +/- 0.2), and did not show any partial agonist
      activity at these peripheral GABAA or GABAB receptor sites. In rat neocortical
      slices, 3-amino-1-nitropropane did not activate GABAB receptor sites or affect
      baclofen-induced suppression of spontaneous discharges. In the cat spinal cord,
      however, under in vivo conditions, the corresponding nitro analog of baclofen 3
      amino-2-(4-chloro)-nitropropane was an agonist at GABAB receptor sites, although
      more than 60 times weaker than baclofen in depressing monosynaptic excitatory
      field potentials, whereas 3-amino-1-nitropropane was an extremely weak agonist at
      bicuculline-sensitive GABAA sites. The differing actions of 3-amino-1
      nitropropane at peripheral and central GABAB receptor sites suggest heterogeneity
      among these receptors.

PMID- 7828643
TI  - Neuroleptics cause stimulation of dopamine D1 receptors and their desensitization
      after chronic treatment.
AB  - Recent evidence indicates that the neuroleptic-induced increase of in vivo
      acetylcholine output in the striatum does not depend on the relief of cholinergic
      neurons from the inhibitory control by dopamine, but on increased dopamine output
      onto dopamine D1 receptors. The present microdialysis study was aimed at finding
      if the neuroleptic-induced increase in striatal acetylcholine release persists
      after chronic treatment, and how it is correlated with dopamine output. Rats were
      chronically treated with the dopamine D2 receptor antagonists, haloperidol and (
      )-sulpiride (0.5 mg/kg and 50 mg/kg i.p., respectively, daily, for 30 days). The
      stimulant effect of both neuroleptics on striatal dopamine release persisted
      unaltered throughout the chronic treatment (by about 100% over basal values). In
      contrast, the enhancing effects of haloperidol and (-)-sulpiride on striatal
      acetylcholine release remained unchanged up to day 12 of treatment. Thereafter,
      tolerance developed, so that both neuroleptics became totally ineffective on day
      30 of treatment. Both on day 1 and 30, the neuroleptic-induced dopamine release
      was reversed by gamma-butyrolactone (gamma-hydroxybutyric acid lactone),
      suggesting that this effect is mediated by enhanced neuronal activity. On day 1
      and day 10, the neuroleptic-induced acetylcholine release was antagonized by the
      blockade of dopamine D1 receptors with SCH 39166 (trans-(-)-(6aS,13bR)-11-chloro
      6,6a,7,8,9,13b- hexahydro-7-methyl-5H-benzo[d]napht[2,1-b]azepine-12-ol,
      hydrochloride) (0.5 mg/kg i.p.). SKF 38393 (1-phenyl-2,3,4,5-tetrahydro-(1H)-3-
      benzazepine-7,8-diol hydrochloride) (5 mg/kg i.p.) increased acetylcholine
      release by about 50% in control rats and in rats treated with (-)-sulpiride or
      haloperidol for up to 7 days.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7828644
TI  - Antinociceptive effect of systemic kelatorphan, in mononeuropathic rats, involves
      different opioid receptor types.
AB  - The antinociceptive effect of i.v. kelatorphan (2.5, 5, 10 and 15 mg/kg), a mixed
      inhibitor of enkephalin degrading enzymes, was studied in a rat model of
      peripheral unilateral mononeuropathy (chronic constriction of the common sciatic
      nerve). Kelatorphan at 2.5 and 5 mg/kg had no significant effect on the
      vocalization threshold to paw pressure test, but higher doses (10 mg/kg) produced
      a significant antinociceptive effect which plateaued at 15 mg/kg, on both
      hindpaws. Kelatorphan (10 mg/kg) was co-injected with the specific mu-, delta-
      and kappa-opioid receptor antagonists naloxone (0.1 mg/kg), naltrindole (1 mg/kg)
      or nor-binaltorphimine (1 mg/kg). The effect of kelatorphan 10 mg/kg was
      completely prevented by naloxone, reduced by 75% by naltrindole (both hindpaws),
      and reduced by 50% by nor-binaltorphimine (contralateral paw only).

PMID- 7828645
TI  - Potentiation of the twitch responses by inhibitors of sarcoplasmic reticulum
      Ca(2+)-ATPase in frog atrial fibres.
AB  - In frog atrial fibres, cyclopiazonic acid as well as thapsigargin, which are
      inhibitors of sarcoplasmic reticulum Ca(2+)-ATPase, induced a significant
      increase in the twitch amplitude without detectable changes in its kinetics. The
      measurements performed on chemically skinned fibres show that cyclopiazonic acid
      has no effect on the properties of contractile proteins. In the presence of a T
      type Ca2+ channel blocker or L-type Ca2+ channel blocker, cyclopiazonic acid
      still induced a potentiation of the twitch while no effect was found in the
      presence of a Na(+)-Ca2+ exchange blocker. The effect of cyclopiazonic acid was
      not related to any modification in myofibrillar Ca2+ sensitivity or in Ca2+
      influx through Ca2+ channels. It is proposed that the inhibition of the
      sarcoplasmic reticulum Ca(2+)-ATPase resulted in a potentiation of the effect of
      the Ca2+ influx and that the major role of the sarcoplasmic reticulum was to
      limit the intracellular Ca2+ concentration.

PMID- 7828646
TI  - Origin of thromboxane-mediated constriction due to neuropeptides in canine
      basilar artery.
AB  - Bradykinin, substance P and vasopressin induced a vasodilatation followed by a
      vasoconstriction in control perfused canine basilar arteries with endothelium.
      The dilatation was significantly reduced and the constriction was significantly
      enhanced by endothelial removal with saponin. The potentiated constriction was
      significantly blocked by sodium ozagrel, a thromboxane synthetase inhibitor.
      These results suggest that the dilatation due to these neuropeptides may depend
      on endothelium-derived relaxing factor, and that the augmented constriction after
      endothelial removal may be related to the thromboxane A2 production in cerebral
      arterial smooth muscles. This mechanism following the damage of endothelium might
      be implicated in cerebral vasospasm after subarachnoid haemorrhage.

PMID- 7828647
TI  - The imidazoline SL 84.0418 shows stereoselectivity in blocking alpha 2
      adrenoceptors but not ATP-sensitive K+ channels in pancreatic B-cells.
AB  - The novel alpha 2-adrenoceptor antagonist SL 84.0418 (2-(4,5-dihydro-1H-imidazol
      2-yl)-1,2,4,5-tetrahydro-2-propyl-pyrrolo[3, 2,1- hi]-indole hydrochloride) is a
      racemic mixture of a (-) enantiomer (SL 86.0714) and a (+) enantiomer (SL 86.0715
      or deriglidole). It was recently reported to inhibit alpha 2-adrenoceptors and
      ATP-sensitive K+ channels in mouse pancreatic B-cells, and to increase insulin
      release. We have now studied the stereospecificity of these responses with
      isolated mouse islets. Both enantiomers were equipotent in potentiating insulin
      release induced by 15 mM glucose alone. SL 86.0714 and deriglidole were also
      equally effective in inhibiting 86Rb efflux from islets perifused with a low
      glucose medium, and in reversing the inhibition of glucose-induced insulin
      release caused by the opening of ATP-sensitive K+ channels with diazoxide. In
      contrast, deriglidole was approximately 100-fold more potent than SL 86.0714 in
      reversing the inhibition of insulin release caused by the activation of alpha 2
      adrenoceptors with clonidine. The effects of SL 84.0418 are thus stereoselective
      on alpha 2-adrenoceptors, but not on ATP-sensitive K+ channels of pancreatic B
      cells.

PMID- 7828648
TI  - Pharmacological similarity between nitric oxide and the nitrergic
      neurotransmitter in the canine ileocolonic junction.
AB  - In organ bath experiments, pyrogallol (30-100 microM), and to a lesser extent L
      cysteine (3 microM), reduced nitric oxide (NO)-induced relaxation, but not the NO
      mediated non-adrenergic non-cholinergic (NANC) relaxation elicited by field
      stimulation of the canine ileocolonic junction. In contrast, in a superfusion
      bioassay, pyrogallol (10-30 microM) and L-cysteine (1 microM) inhibited the
      biological activity of both the transferable nitrergic factor released from the
      canine ileocolonic junction in response to NANC nerve stimulation and NO, but not
      that of S-nitroso-L-cysteine, S-nitrosoglutathione or S-nitroso-N-acetyl-D,L
      penicillamine. Based on the bioassay experiments, it is concluded that the
      nitrergic NANC neurotransmitter in the canine ileocolonic junction behaves
      pharmacologically like NO.

PMID- 7828649
TI  - Possible physiological role of endogenous adenosine in defecation in rats.
AB  - Evacuated feces after intraperitoneal administration of selective adenosine
      receptor antagonists were evaluated in rats. The selective adenosine A1 receptor
      antagonists, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) (100-300 micrograms/kg
      i.p.) and (R)-7,8-dihydro-8-ethyl-2-(3-noradamantyl)-4-propyl-1H-imidazo[2,1 
      i]purin- 5(4H)-one (KF20274) (30-300 micrograms/kg i.p.), significantly increased
      defecation, whereas the selective adenosine A2 receptor antagonist 4-amino-8
      chloro-1-phenyl[1,2,4]triazolo[4,3-a]quinoxaline (CP-66,713) failed to cause a
      significant increase at up to 10 mg/kg i.p. The defecation caused by DPCPX (100
      micrograms/kg) was markedly alleviated by (2S)-N6-(2-endo-norbornyl)adenosine
      ((S)-ENBA) (30-300 micrograms/kg s.c.), a selective adenosine A1 receptor
      agonist, but not influenced by 2-[p-(2-carboxyethyl)phenethylamino]-5'-N
      ethylcarboxamidoadenosin e (CGS 21680) (30-1000 micrograms/kg s.c.), a selective
      adenosine A2 receptor agonist. These results suggest that endogenous adenosine
      plays a physiological role in sustained inhibition of defecation via adenosine A1
      receptors.

PMID- 7828650
TI  - Inhibition of 8-OH-DPAT-induced elevation of plasma corticotrophin by the 5-HT1A
      receptor antagonist WAY100635.
AB  - Numerous studies have demonstrated the stimulatory effect of 5-HT1A receptor
      agonists, such as 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), on plasma
      corticotrophin (ACTH) levels in the rat. However, until recently the lack of a
      selective 5-HT1A receptor antagonist has hampered mechanistic studies in this
      area. In this study we examined the effects of the selective 5-HT1A receptor
      antagonist N-[2-[4-(2-methoxyphenyl)-1- piperazinyl]ethyl]-N-(2-pyridinyl)
      cyclohexanecarboxamide trihydrochloride (WAY100635) on plasma ACTH levels and on
      the elevation of ACTH induced by the 5-HT1A receptor agonist 8-OH-DPAT in the
      conscious rat. The basal plasma ACTH level was 41.0 +/- 1.8 pg/ml. 8-OH-DPAT
      increased ACTH levels at doses of 100 and 300 micrograms/kg with maximum
      increases of 551 and 546% respectively occurring 10 min post-injection. WAY100635
      had no effects per se on plasma ACTH at doses up to 100 micrograms/kg, indicating
      it has no 5-HT1A receptor agonist properties. WAY100635 dose-dependently blocked
      the elevation of ACTH induced by 8-OH-DPAT, the minimum effective dose being 10
      micrograms/kg. The present results indicate that 8-OH-DPAT elevates plasma ACTH
      levels by stimulating 5-HT1A receptors, a conclusion that is consistent with the
      findings of previous studies using non-selective 5-HT1A receptor antagonists such
      as pindolol.

PMID- 7828651
TI  - Inhibition by two lavendustins of the tyrosine kinase activity of pp60F527 in
      vitro and in intact cells.
AB  - The mutant pp60F527 protein possesses an activated protein-tyrosine kinase (PTK)
      activity correlated with a transforming activity. We have studied the inhibition
      of the pp60F527 PTK activity by two EGF-R tyrosine kinase inhibitors, lavendustin
      A and one of its derivatives, lavendustin C6. In vitro, both molecules were non
      competitive inhibitors for the ATP binding site and uncompetitive inhibitors for
      the peptide binding site. The determined IC50S of the inhibition of pp60F527
      kinase activity were 18 microM for lavendustin A and 5 microM for lavendustin C6,
      as determined on the exogenous substrate enolase, showing that lavendustin C6 was
      more potent than lavendustin A. Lavendustin C6, but not lavendustin A, inhibited
      the tyrosine phosphorylation of pp60F527 cellular substrates (the GAP-associated
      p190, pp125FAK and cortactin) in intact cells. However, this in situ inhibitory
      effect did not result in a reversion of the morphological changes induced by
      pp60F527 in cells. On the other hand, lavendustin C6 and lavendustin A exerted
      antiproliferative effects on cells, suggesting that inhibition of cellular
      targets related or not to the kinase was also possible.

PMID- 7828652
TI  - Inhibition of L-type Ca2+ channels in portal vein myocytes by the enantiomers of
      oxodipine.
AB  - We studied the effects of the enantiomers of the dihydropyridine derivative, 4
      (2,3 methylenedioxyphenyl)-1,4-dihydro-2,6-dimethyl-3 carboxyethyl-5
      carboxymethyl-pyridine (oxodipine), on voltage-dependent Ca2+ channels of rat
      portal vein myocytes by combining electrophysiological techniques and binding
      studies. (+)- and (-)-oxodipine depressed the L-type Ca2+ current in a
      concentration-dependent manner, with similar IC50 values (around 10 nM) but had
      no appreciable effect on the intracellular Ca2+ stores. The steady-state
      inactivation curve for the Ca2+ current was shifted along the voltage axis to
      negative membrane potentials indicating that the block of the Ca2+ current by
      oxodipine enantiomers increased with depolarization. The voltage-dependent
      inhibitory property of oxodipine was related to an increase in [3H](+)-4-(benzo-2
      oxa-1,3-diazol-4-yl)-1,4-dihydro-2,6-dimethy lpy ridine- 3,5-dicarboxylic acid 3
      isopropyl, 5-methyl ester (isradipine) binding affinity without change in binding
      capacity. In normally polarized intact strips, interactions of (+)- and (-)
      oxodipine with [3H](+)-isradipine binding indicated a stimulation of the
      radioligand binding at low concentrations of (-)-oxodipine while the (+)
      enantiomer seemed to act as a competitive ligand. Depolarization of intact strips
      with 135 mM K(+)-solutions increased the apparent affinity of the enantiomers of
      oxodipine, and abolished the stimulating effect of (-)-oxodipine on the binding
      of [3H](+)-isradipine. Inhibition of Ca2+ current was increased in the
      simultaneous presence of 1 nM of (+)- and (-)-oxodipine when compared to the
      inhibitions induced by 2 nM of each enantiomer.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7828653
TI  - Role of angiotensin II in extracellular matrix and transforming growth factor
      beta 1 expression in hypertensive rats.
AB  - The in vivo effects of alacepril (1-[(S)-3-acetylthio-2-methylpropanoyl]- L
      prolyl-L-phenylalanine), an angiotensin converting enzyme inhibitor, and SC-52458
      (5-[(3,5-dibutyl-1H-1,2,4-triazol-1- yl)methyl]-2-[2-(1H-tetrazol-5
      ylphenyl)]pyridine), an angiotensin AT1 receptor antagonist, were examined on the
      cardiac and aortic gene expressions of extracellular matrices and TGF-beta 1 in
      young spontaneously hypertensive rats (SHR). In SHR, types I and III collagen
      mRNAs were increased in the left ventricle, and in contrast, fibronectin,
      collagen IV, and transforming growth factor-beta 1 (TGF-beta 1) mRNAs were
      increased in aorta, compared with those in Wistar-Kyoto rats. All the enhanced
      mRNAs in both organs in SHR were significantly inhibited by the short-term
      treatment with the above two drugs. Thus, angiotensin AT1 receptor may play an
      important role in the regulation of extracellular matrices and TGF-beta 1
      expressions in SHR.

PMID- 7828654
TI  - Dopamine D1 receptor agonists display a different intrinsic activity in rat,
      monkey and human astrocytes.
AB  - Measuring dopamine D1 receptor stimulated cyclic AMP production in cultured
      astrocytes from rat, monkey and human brain, we demonstrate that the 'classical'
      drug SKF 38393 (7,8-dihydroxy-1- phenyl-2,3,4,5-tetrahydro-1 H-3-benzazepine) is
      a partial agonist with particularly low intrinsic activity in primates.
      Furthermore, its analogue SKF 81297 (6-chloro-7,8-dihydroxy-1-phenyl-2,3,4,5-
      tetrahydro-1 H-3-benzazepine) is shown to be a full agonist in rats but a
      partial, albeit more efficacious, agonist in primates, whereas the benzopyran A
      68930 ((1R,3S)-1-aminomethyl-5,6- dihydroxy-3-phenyl-isochroman HCl) displays
      full efficacy in both species. The data suggest that cultured astrocytes provide
      a good model to study species differences in the pharmacological characteristics
      of dopamine D1 receptor agonists and indicate that SKF 38393 is not suited to
      study dopamine D1 receptor function in primates.

PMID- 7828655
TI  - Dopamine receptor blockade increases dopamine D2 receptor and glutamic acid
      decarboxylase mRNAs in mouse substantia nigra.
AB  - To study the influence of dopaminergic activity on the expression of dopamine D2
      receptors and glutamic acid decarboxylase in substantia nigra, mice were treated
      daily for several days with an irreversibly acting dopamine D1 and dopamine D2
      receptor antagonist N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) or with
      a selective irreversible D2 dopamine receptor antagonist fluphenazine-N-mustard.
      Mice were killed 24 h after the last injection. Dopamine D1 and dopamine D2
      receptors were determined by receptor autoradiography, and dopamine D1 and
      dopamine D2 receptor mRNA and glutamic acid decarboxylase mRNA were determined by
      in situ hybridization histochemistry. The results showed that treatment with
      EEDQ, which blocked 80% to 85% of the dopamine D2 and dopamine D1 receptors in
      substantia nigra, increased the levels of dopamine D2 receptor mRNA in substantia
      nigra by about 27%. Treatment with fluphenazine-N-mustard, which blocked about
      85% of the dopamine D2 receptors in substantia nigra but had no significant
      effect on dopamine D1 receptors, increased the levels of dopamine D2 receptor
      mRNA by about 34%. There were no detectable levels of dopamine D1 receptors,
      increased the levels of dopamine D2 receptor mRNA by about 34%. There were no
      detectable levels of dopamine D1 receptor mRNA in substantia nigra either in
      control animals or in animals treated with the dopamine receptor antagonists.
      Glutamic acid decarboxylase mRNA was expressed in several regions of the mid
      brain but only that expressed in substantia nigra was altered by treatment with
      dopamine receptor antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7828656
TI  - High affinity [3H]formoterol binding sites in lung: characterization and
      autoradiographic mapping.
AB  - Agonist binding to the beta 2-adrenoceptors and its mapping were studied using
      the newly developed radioligand [3H]formoterol. The results of [3H]formoterol
      saturation binding and formoterol inhibition of [3H]formoterol binding were
      consistent with binding to a single class of receptors (Kd = 1.34 +/- 0.15 nM,
      Bmax = 154.9 +/- 8.0 fmol/mg protein in guinea pig lung membranes, n = 8; Kd =
      1.05 +/- 0.17 nM, Bmax = 67.8 +/- 8.1 fmol/mg protein in human lung membranes, n
      = 5) and competition assays with other agonists and antagonists disclosed only a
      single class of site. The nonhydrolyzable GTP analogue GTP gamma S caused a
      reduction in both Kd and Bmax, indicating that the receptors labelled by
      [3H]formoterol are coupled to a guanine nucleotide binding regulatory protein.
      Receptor mapping of [3H]formoterol binding sites shows that beta 2-adrenoceptors
      were widely distributed in both guinea pig and human lung, with dense labelling
      over airway epithelium and uniformly over alveolar walls, and sparse labelling of
      airway and vascular smooth muscle. In addition, submucosal glands were also
      sparsely labelled in human bronchus. The distribution of beta 2-adrenoceptors was
      similar to the pattern previously described with non-selective radiolabelled
      antagonists in the presence of selective beta 1-adrenoceptor antagonists.

PMID- 7828657
TI  - Selective block of recombinant glur6 receptors by NS-102, a novel non-NMDA
      receptor antagonist.
AB  - The diversity of neuronal glutamate receptors continues to increase with the
      discovery of multiple subunits and subunit families. The significance of this
      potential receptor heterogeneity is unknown because pharmacological tools that
      could clearly distinguish between different structural isoforms have not yet been
      identified. A novel glutamate receptor antagonist, 5-nitro-6,7,8,9
      tetrahydrobenzo[g]indole-2,3-dione-3-oxime (NS-102), has been shown previously to
      selectively block the low affinity [3H]kainate binding site in rat brain. We have
      examined the effect of NS-102 on receptors expressed in fibroblasts from either
      glur6 subunits or a combination of glurB and glurD (glurB/D receptors). NS-102 (3
      microM) reduced currents mediated by glur6 receptors and had very little effect
      on currents mediated by glurB/D receptors. The binding of [3H]kainate to glur6
      receptors showed properties similar to those of the brain low affinity
      [3H]kainate binding site, and NS-102 inhibited specific binding to glur6
      receptors with a potency nearly identical to those sites in brain membranes. Our
      findings suggest that NS-102 will be useful in identifying the functional role of
      native receptors containing a glur6 subunit.

PMID- 7828658
TI  - Characterization of the adenosine receptor in microvascular coronary endothelial
      cells.
AB  - In the present work we studied the effect of adenosine and various adenosine
      analogues on cAMP level in guinea pig coronary endothelial cells of microvascular
      origin. The tested adenosine agonist mediate a concentration-dependent increase
      in cAMP level. The rank order of potency was 5'-N-ethylcarboxamidoadenosine
      (NECA) > CGS 21680 > N6-phenylisopropyladenosine (R-PIA) > 2-chloro-N6
      cyclopentyladenosine (CCPA) which is typical for an adenosine A2 receptor. Their
      respective concentrations for half maximal stimulation of cAMP formation were
      0.36 microM, 0.82 microM, 4.7 microM and 9.8 microM. The tested agonists showed
      differences in efficacy, NECA being the most efficacious. R-PIA, CCPA and
      adenosine were less efficacious, suggesting partial agonism. The efficacy of
      adenosine was unchanged by the addition of the nucleoside transport inhibitor S(4
      nitrobenzyl)-6-thioinosine (NBTI, 10 microM) suggesting that inhibition of
      adenylyl cyclase through P-site activation is not responsible for the observed
      low efficacy of adenosine. We could demonstrate CGS 21680 activation of adenylyl
      cyclase in a peripheral receptor. We therefore suggest that the endothelial
      adenosine receptor resembles the striatal adenosine A2a receptor.

PMID- 7828659
TI  - Association of guinea pig lung bombesin receptors with pertussis toxin-sensitive
      guanine nucleotide binding proteins.
AB  - The possible interaction of bombesin receptors with guanine nucleotide binding
      protein in guinea pig lung was studied. The non-hydrolysable GTP analogue
      guanosine-5'-[gamma-thio]triphosphate (GTP gamma S) was shown to decrease [125I
      Tyr4]bombesin binding in a concentration-dependent manner. The specificity of
      this effect was assessed by examining the effects of other guanine nucleotides on
      this binding at a concentration of 1 mM. GMP and GDP weakly inhibited [125I
      Tyr4]bombesin binding (2 and 19%, respectively), whereas GTP, guanosine-5'-[beta
      thio]triphosphate (GDP beta S), and 5-guanylylimidodiphosphate (GppNHp) exhibited
      similar potencies, inducing 52%, 46%, and 43% inhibition of [125I-Tyr4]bombesin
      binding respectively. Saturation experiments performed in the absence and
      presence of 100 microM GTP gamma S indicated the presence of a single population
      of receptors in both cases. However, the addition of GTP gamma S induced a marked
      decrease in the number of receptors (from 1.76 fmol/mg protein to 0.78 fmol/mg
      protein) without significantly altering the dissociation constant (Kd). These
      results provide evidence that bombesin receptors are coupled to a G-protein
      signal transduction pathway in guinea pig lung. We have further characterised
      this G-protein on the basis of its toxin sensitivity. Pretreatment of the lung
      membranes with either pertussis (10 micrograms/ml) or cholera toxin (50
      micrograms/ml) was performed. Cholera toxin treatment did not affect the ability
      of GTP gamma S to inhibit [125I-Tyr4]bombesin binding to guinea pig lung
      membranes. However, pertussis toxin treatment induced a decrease in binding and
      resulted in the inability of GTP gamma S to inhibit [125I-Tyr4]bombesin binding
      in a concentration-dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7828660
TI  - Pharmacological analysis of carboxyphenylglycines at metabotropic glutamate
      receptors.
AB  - Three carboxyphenylglycine derivatives were examined for their activity on
      glutamate metabotropic receptors negatively linked to adenylate cyclase. Chinese
      hamster ovary cells stably expressing mGlu2 and mGlu4 were utilised for this
      study. A receptor binding analysis was also performed for the main classes of
      glutamate ionotropic receptors and for the glycine binding site on the NMDA
      receptor complex. In mGlu2 expressing cells (S)4-carboxy-3-hydroxyphenylglycine
      and (S)4-carboxy-phenylglycine antagonized forskolin-stimulated cAMP levels, with
      EC50 of 21 and 970 microM, respectively, acting as agonists at this receptor
      subtype, whereas (RS) alpha-methyl-4-carboxyphenylglycine antagonized glutamate
      response in these cells. None of these compounds showed any agonistic or
      antagonistic activity on mGlu4 expressing cells. No affinity for the ionotropic
      receptors (NMDA, AMPA and kainate) and for the glycine site of the NMDA-receptor
      complex was found using the receptor binding approach, except for (RS)4-carboxy-3
      hydroxyphenylglycine which showed a pKi of 5.68 in ((+/-)2-carboxypiperazin-4
      yl)propyl-1-phosphonic acid binding for NMDA receptor, although this can be
      ascribed to the (R) form of the racemic mixture.

PMID- 7828661
TI  - Adipocyte alpha 2A-adrenoceptor is the only alpha 2-adrenoceptor regulated by
      testosterone.
AB  - The effects of chronic administration of testosterone on alpha 2-adrenoceptor
      expression in male hamsters were investigated in order to explore the selectivity
      of testosterone regulation towards the alpha 2-adrenoceptor subtypes. A
      homogeneous population of alpha 2-adrenoceptors was identified with [3H]RX821002
      binding in adipocytes, colocytes and liver, whereas the alpha 2-adrenoceptor
      sites identified in kidney and brain were heterogeneous. Competition studies with
      alpha 2-adrenoceptor ligands characterized the presence of the alpha 2A
      adrenoceptor subtype in adipocytes, colocytes, kidney and brain homogenates and
      of the alpha 2B-adrenoceptor subtype in kidney and liver. RNase protection assay
      with a selective hamster alpha 2A-adrenoceptor cRNA probe confirmed the
      expression of alpha 2A-adrenoceptor mRNA in adipocytes, colocytes, kidney and
      brain. Testosterone treatment did not modify the alpha 2-adrenoceptor densities
      whatever the subtype, except for the adipocyte alpha 2A-adrenoceptor, which was
      significantly increased. These results demonstrate that testosterone only up
      regulates the adipocyte alpha 2A-adrenoceptor.

PMID- 7828662
TI  - Age-related changes in immune parameters in a very old population of Swedish
      people: a longitudinal study.
AB  - This study used a longitudinal design to examine age-related changes in a well
      defined sample of Swedish people ranging from 86 to 92 years of age at baseline.
      The longitudinal design encompassed three measurement occasions with 1 year
      intermeasurement intervals. The results were analyzed by multivariate analyses of
      variance (MANOVA), which is useful for comparing individuals over time. Healthy
      middle-aged subjects (39 years SD +/- 5.8) served as controls. The proliferative
      responses to Concanavalin A (Con A), a T-cell mitogen, indicated significant
      lower levels in responses of the old when the two groups were compared. The
      MANOVA revealed no significant change in mitogen responses over measurement
      occasions in the old sample as compared with the young. However, when cell types
      and lymphocyte subpopulations were examined, significant differences were found
      between the two age groups in many of these parameters and for some (lymphocyte
      percentages and numbers, CD3 numbers) the MANOVA indicated significant decreases
      over the measurement occasions in the very old. The results also consistently
      indicated significant intraindividual correlations in cell types, lymphocyte
      subpopulations, and mitogen responses over time.

PMID- 7828663
TI  - Morphological studies of growth and aging in the lungs of Fischer 344 male rats.
AB  - Observations by light microscopic morphometry and scanning electron microscopy
      were performed on the lungs from 86 specific pathogen-free Fischer 344 male rats
      between 1 day and 32 months of age. The distribution curve of the mean chord
      length of the gas exchanging area appeared as a single peak (approximately 70
      microns) at day 1, and two peaks (approximately 50 and 90 microns) were seen at
      day 7 when the first alveoli appeared. At 3 months of age, the distribution curve
      peaks began to decrease gradually, becoming more flattened with a wide base to a
      maximum 200 microns. Between 27 and 32 months of age, ductectasia occurred and
      the alveolar surface appeared more irregular and rough, but no destruction of the
      alveolar wall was observed. From these observations, it was concluded that the
      first alveoli appear by 7 days of age in male Fischer 344 rats, that the alveolar
      size gradually increases after 3 months of age, and that ductectasia appears
      after 27 months of age. These changes might reflect changes in the matrix of the
      alveolar walls due to nutritional deterioration in old age, concomitant with
      cellular atrophy of this zone.

PMID- 7828664
TI  - Effect of long-term acetyl-L-carnitine on stress-induced analgesia in the aging
      rat.
AB  - Cold water swim (CWS) analgesia in the rat is mediated by the hypothalamo
      pituitary-adrenocortical (HPA) axis. An age-dependent increase of CWS-induced
      analgesia was observed in male Sprague-Dawley young (4 months), adult (15 months)
      and old (26 months) rats. Acetyl-L-Carnitine (ALCAR) chronically administered (75
      mg/kg/daily in drinking water for 8 months) to old rats was able to maintain the
      stress-dependent response at the same levels as in adult rats. This effect may be
      explained by ALCAR capability of retarding the age-dependent loss of
      glucocorticoid receptors in the hippocampus, thus maintaining the glucocorticoid
      competence of this structure which exerts a negative feedback control over the
      HPA axis activity.

PMID- 7828665
TI  - Alterations in free radical activity in aging Drosophila.
AB  - Drosophila were examined to see if there is an increase in damage associated with
      free radical activity in older flies. The levels of superoxide radical and of
      lipid peroxides were higher in membrane samples from older flies. Also, in older
      Drosophila there was a significant decrease in membrane fluidity, as determined
      by fluorescence polarization, and an increase in ATP-dependent calcium uptake. In
      homogenates from whole flies, the concentration of inorganic peroxides and
      activity of the proteolytic enzyme, cathepsin B, increased with age. During their
      lifetime, vestigial wing Drosophila displayed a greater level of free radical
      activity than wild-type flies and a significantly shorter life span (26.7 +/- 0.7
      days vs. 34.4 +/- 1.0, p < 0.01). These results indicate that the level of
      oxidative stress is closely coupled to cellular damage and to life span, and they
      indicate that free radicals may play a central role in the aging process in
      Drosophila.

PMID- 7828666
TI  - Effect of BHA on longevity, antioxygenic enzymes and peroxides in Callosobruchus
      maculatus.
AB  - Life span and antioxygenic enzyme activities of insects reared on optimal BHA
      concentration (1 mM) soaked seeds were higher than their respective controls.
      However, the reproductive potential, peroxides and the level of free radicals
      declined. The increased longevity with BHA could be attributed to its free
      radical quenching effect, thereby leading to the decreased peroxide levels and
      the increased antioxygenic enzyme activities of the insects.

PMID- 7828667
TI  - Studies on the hyperthermic sensitivity of the murine hematopoietic stem cell
      compartment. II. Heat effect on donor stem cells with long-term repopulating
      ability.
AB  - Variations in hyperthermic sensitivity among different hematopoietic progenitor
      and stem cell populations of the bone marrow have been previously described for
      clonogenic subsets responsible for short-term hematopoiesis. However, less is
      known of the heat sensitivity of more primitive stem cells capable of long-term
      repopulation in irradiated recipients. In the present study, control and heat
      treated (60 minutes at 43 degrees C) donor bone marrow cells from congenic B6-Gpi
      1a mice were transplanted at different cell doses (10(4), 10(5), 10(6), and 10(7)
      nucleated cells) in pre-irradiated (6 Gy) B6-Gpi-1b mice. The development and
      levels of donor marrow engraftment were determined from blood Gpi phenotyping,
      and the bone marrow dose required for equivalent long-term engraftment at 20
      weeks provided an estimate of the surviving fraction corresponding to primitive
      stem cells of long-term repopulating ability (LTRA). Comparison with previous
      bone marrow cell survival values demonstrates that LTRA cells are less sensitive
      to hyperthermic treatment than other hematopoietic subsets, confirming a
      relationship between the heat sensitivity and the hierarchical structure of the
      hematopoietic stem cell compartment.

PMID- 7828668
TI  - O6-benzylguanine increases the sensitivity of human primary bone marrow cells to
      the cytotoxic effects of temozolomide.
AB  - The sensitivity of human primary bone marrow granulocyte/macrophage precursor
      cells to the cytotoxic effects of the methylating antitumor agent temozolomide (8
      carbamoyl-3- methylimidazo[5,1-d]-1,2,3,5-tetrazin-4-[3H]-1) was investigated
      using an in vitro colony-forming assay. In the eight samples examined, there was
      a range of sensitivities with D37 values from 18.2 to > 55 microM. When cells
      were simultaneously exposed to the O6-alkylguanine-DNA alkyltransferase (ATase)
      inactivating agent, O6-benzylguanine (O6BeG; 10 microM), the cytotoxicity of
      temozolomide was substantially increased with D37 values between 5 and 38.5
      microM. O6BeG also increased temozolomide sensitivity in the human colon
      carcinoma cell line, WiDr, and this was shown to correlate with the O6BeG
      mediated depletion of ATase activity. Where the extent of sensitization produced
      by O6BeG could be calculated, there was a correlation between this and the D37
      value in the absence of O6BeG (R = 0.996); thus, sensitization was more extensive
      in the cells that were inherently more resistant to temozolomide. These data have
      implications for possible increased hematological toxicity in clinical protocols
      designed to exploit O6BeG or other agents to deplete ATase activity in tumors
      cells prior to treatment of patients with temozolomide or related agents.

PMID- 7828669
TI  - Characterization of M-CSF and its receptor in microphthalmic mice.
AB  - The macrophage colony-stimulating factor (M-CSF) gene expression in osteopetrotic
      mice (op/op) is defective due to a point-mutation in the M-CSF gene [1]. However,
      almost all osteopetrotic patients have been shown to have a normal or elevated
      circulating level of bioactive M-CSF [2]. To investigate the action of the M-CSF
      in mi/mi mice (microphthalmic; another osteopetrotic mouse mutant), M-CSF levels
      and its receptors were studied. We found that serum levels of M-CSF in mi/mi mice
      were not significantly different from normal control mice. The M-CSF receptor
      binding affinity of spleen-adherent cells was similar to that of control mice. In
      spleen cells from mi/mi mice, the receptor binding sites per cell (normalized to
      total spleen cells, M-CSF receptor positive cells, or M-CSF receptor RNA positive
      cells) were present in a greater number than in spleen cells from phenotypically
      normal siblings. Northern blot analysis showed that there is no significant
      difference in transcripts of the M-CSF receptor (c-fms) in the mi/mi and
      phenotypically normal mice. Unlike the op/op mutant, M-CSF levels, as well as the
      affinity and number of M-CSF receptors, do not explain the defect in osteoclastic
      function in the mi/mi mutation.

PMID- 7828670
TI  - Nontransformed colony-derived stromal cell lines from normal human marrows. II.
      Phenotypic characterization and differentiation pathway.
AB  - In a previous report, we described a method to generate cell lines derived from
      stromal colonies (colony-derived cell lines [CDCL]). In a first step, colonies
      were obtained from plating cells from adherent layers of human long-term bone
      marrow cultures (LTBMC) in methyl-cellulose in the presence of interleukin-1 beta
      (IL-1 beta) (20 U/mL) and tumor necrosis factor-alpha (TNF-alpha) (200 U/mL). In
      a second step, cell lines were derived from individual colonies cultured in
      liquid medium with 20 ng/mL basic fibroblast growth factor (bFGF). In this
      report, we describe the phenotype of cells from more than 100 cell lines. CDCL
      did not contain cells of hematopoietic origin, which indicates that the culture
      system did not allow the growth of hematopoietic precursors. CDCL did not contain
      endothelial-like cells, similarly to primary adherent layers. CDCL comprised
      stromal cells, as defined by membrane antigens recognized by monoclonal
      antibodies 6-19, Stro-1 and 1B10. These cells belonged to the family of
      connective tissue-forming cells since they synthesized interstitial collagens I,
      III, and V; nonplasmatic EDa+ and EDb- fibronectin; tenascin; and chondroitin
      sulfate. Study of the time course of CDCL showed that the lines differed from one
      another according to their proliferative capacity: 32% of CDCL grew quickly,
      yielding about 10,000 cells in 10 days; 36% of CDCL grew slowly, yielding 1000
      cells in 10 days; and the remaining 32% had intermediate proliferative capacity.
      For CDCL with a high proliferative capacity, a distinctive differentiation
      pattern could be described. At culture, inception cells from the lines were
      vimentin and laminin. Over time, several cytoskeletal and extracellular matrix
      (ECM) proteins indicative of vascular smooth muscle differentiation were
      expressed, including: the alpha-SM-actin isoform; the actin-binding proteins,
      smooth muscle myosin-heavy chain (SMMHC), SM1; h-caldesmon; calponin; gelsolin;
      and the ECM proteins, collagen IV and elastin. In full-grown lines, cells were
      similar to immature, intimal, vascular smooth muscle cells as found beneath the
      endothelium in adult aortas. Because of the coupling between proliferation and
      differentiation, the differentiation pattern seems to be under genetic control.
      However, since the coupling was not stringent during the whole lifespan of the
      lines, it is possible that cytokines are also involved, ensuring autocrine
      regulation of CDCL development.

PMID- 7828671
TI  - Developmental hematopoiesis from prenatal to young-adult life in the mouse model.
AB  - Five measurements of hematopoietic function were made in the mouse from midfetal
      life to young adulthood. These included two in vivo (day-8 colony-forming unit
      spleen [CFU-S8] and day-12 CFU-S [CFU-S12]) and two in vitro clonal measurements
      of hematopoietic stem and progenitor cells (high proliferative potential colony
      forming cell [HPP-CFC] and CFC of low proliferative potential [LPP-CFC]) as well
      as an in vitro clonal measurement of colony-forming unit-fibroblast (CFU-F). The
      appearance, increase, subsequent decrease, and later emergence and increase of
      each of these parameters in the fetal-liver, newborn, growing-infant, and young
      adult bone marrow were correlated and found to be in parallel. Exceptions to this
      included the earlier appearance in the fetal liver of CFU-F and the relatively
      differentiated hematopoietic LPP-CFC. The pattern of emergence of these
      progenitor cell subpopulations in the fetal liver may be related, in part to the
      timing of the hematopoietic microenvironment development and the relative
      frequencies of progenitor cell types in the circulation. This developmental study
      in the mouse model describes additional correlations between in vivo and in vitro
      colony-forming stem cells and fibroblastic stromal colony-forming cells, and it
      suggests the dependence of hematopoietic stem cells upon the stromal
      microenvironment for the necessary conditions for hematopoietic stem cell
      lodgment, growth, and maturation.

PMID- 7828672
TI  - Leukemic cells (HL-60) produce a novel extracellular matrix-degrading proteinase
      that is not inhibited by tissue inhibitors of matrix metalloproteinases (TIMPs).
AB  - In addition to the known 94-kd gelatinase (matrix metalloproteinase 9, MMP-9), HL
      60 leukemia cells release a hither-to undescribed 45-kd metalloproteinase into
      the culture medium. This enzyme cleaves the synthetic substrate Pro-Gln-Gly-Ile
      Ala-Gly-Gln-Arg, which represents the cleavage site for collagenases in collagen
      type I not between isoleucine and alanine--the typical cleavage site for
      collagenases--but between alanine and glycine. The enzymatic activity was
      purified through a combination of zinc-chelate-Sepharose column chromatography,
      precipitation with Fractogel TSK-AF Red and gelatin-Sepharose, and subsequent
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE).
      Microsequence analysis of the NH2-terminus of the purified 45-kd proteinase
      revealed the sequence Asp-Ile-Ser-Lys-Tyr-Thr-Thr-Thr-, which could not be found
      in other proteins when searched in several protein data bases. Incubation of the
      enzyme immobilized on nitrocellulose membranes with polyclonal antibodies to
      collagenase and stromelysin or gelatinases revealed no cross-reactivity. The
      proteolytic activity was not increased by treatment with trypsin, 8M urea, acid,
      or organomercurials. The proteinase, which was inhibited by chemical inhibitors
      of metalloproteinases, such as phenanthrolene or EDTA, is able to degrade several
      matrix constituents, such as collagen type IV, fibronectin, gelatin, and
      proteoglycans. In contrast to all known MMPs, the proteolytic activity of the 45
      kd enzyme was not abolished upon incubation with recombinant tissue inhibitors of
      matrix metalloproteinases (TIMP) 1 or 2. Thus, the novel enzyme may influence
      extracellular matrix (ECM) turnover in vivo because its activity is not
      influenced by specific inhibitors of MMPs.

PMID- 7828673
TI  - Modified thrombopoietic response to 5-FU in mice following transplantation of Lin
      Sca-1+ bone marrow cells.
AB  - An experimental murine model of bone marrow transplantation (BMT) has been used
      to study the mechanisms of platelet production following transplantation. A
      defined primitive population of hematopoietic bone marrow cells (1000 Lin-Sca-1+)
      was isolated and transplanted into lethally irradiated (13 Gy) syngeneic
      recipient mice. Platelet counts, but neither red nor white blood cell (WBC)
      counts, were low 30 days after transplantation. By 90 days, platelet levels had
      normalized in transplanted mice, but this occurred from a reduced megakaryocyte
      progenitor (CFU-Mk) pool, implying that altered bone marrow control was involved
      in platelet production. To assess the capacity of the bone marrow of these
      compensated mice to sustain platelet production, the rate and degree of recovery
      were examined following administration of 150 mg/kg of 5-fluorouracil (5-FU) 90
      days after transplantation. Transplanted mice showed a delay, both in platelet
      recovery and rebound thrombocytosis, after 5-FU administration when compared to
      normal littermates treated with 5-FU. The regeneration and expansion of bone
      marrow CFU-Mk and mature megakaryocytes was retarded in the transplanted mice and
      explained the altered platelet kinetics. The onset of increased platelet and
      mature megakaryocyte size, however, was not different between the two groups,
      indicating that the transplanted mice responded normally to the mechanisms
      controlling megakaryocyte development and platelet formation. The data suggest
      that following BMT a limitation in the proliferative capacity of primitive
      hematopoietic cells results in a smaller pool of megakaryocyte precursors.
      Compensatory adjustment within the megakaryocyte lineage, nevertheless, results
      in normalization of megakaryocyte and platelet number. The ability of
      transplanted mice to sustain platelet production when challenged with increased
      platelet demand is not limited by megakaryocytic maturation but by a restriction
      in proliferation or differentiation from the stem cell pool.

PMID- 7828674
TI  - Influence of alloreactive T cells on initial hematopoietic reconstitution after
      marrow transplantation.
AB  - One possible mechanism by which donor T cells might facilitate allogeneic marrow
      engraftment is through the production of lymphokines or cytokines that promote
      proliferation and differentiation of hematopoietic stem cells. To address this
      hypothesis, we have tested whether alloactivated donor T cells can accelerate
      initial engraftment in mice when limiting numbers of marrow cells were given to
      recipients in parent-->F1 strain combinations where rejection is not a limiting
      factor. Lethally irradiated (11 Gy) F1 recipients were transplanted with grafts
      composed of 1 x 10(6) T cell-depleted parental marrow cells with no T cells added
      or with 1 to 2 x 10(6) purified CD3+ parental or F1 lymph node cells added.
      Parental T cells capable of causing graft-vs.-host disease (GVHD) slowed the rate
      of initial engraftment, as measured by the number of nucleated cells in the
      marrow between 7- and 14-days posttransplantation, while F1 T cells had no effect
      compared to controls transplanted without T cells in the graft. Both F1 and
      parental T cells caused an increase in peripheral blood leukocyte counts first
      apparent at 2 weeks posttransplantation. Splenic erythropoiesis as measured by
      59Fe incorporation was not affected by either parental or F1 T cells during the
      first 2 weeks posttransplantation. The slower marrow reconstitution in recipients
      transplanted with parental T cells may have several explanations that are not
      mutually exclusive. Elaboration of tumor necrosis factor (TNF), interferon-gamma
      (INF-gamma), or transforming growth factor-beta (TGF-beta) by activated T cells
      may directly inhibit hematopoiesis or may interfere with the production of
      another cytokine necessary for hematopoiesis. Inflammatory mediators elaborated
      during the initiation of GVHD may also promote early mobilization of cells from
      the marrow into the blood. Finally, GVHD could cause damage to the hematopoietic
      microenvironment.

PMID- 7828675
TI  - GATA transcription factors: key regulators of hematopoiesis.

PMID- 7828676
TI  - The pathogenesis of airway colonization: lessons learned from the study of
      bacterial adherence.

PMID- 7828677
TI  - Sleep apnoea--evolution and doubt.

PMID- 7828678
TI  - Assessment of respiratory muscle function.

PMID- 7828679
TI  - Interaction of Pseudomonas aeruginosa with human respiratory mucosa in vitro.
AB  - Pseudomonas aeruginosa commonly infects the airways of patients with cystic
      fibrosis and bronchiectasis. It produces several toxins that slow ciliary beat,
      stimulate mucus production and damage epithelium. It adheres to epithelial cells,
      damaged mucosa (in animal models), and mucus. However, little is known of the
      interaction of P. aeruginosa with intact human respiratory mucosa. We have
      studied the interactions of a nonmucoid clinical isolate of P. aeruginosa with
      adenoid tissue in a novel organ culture model with an air-mucosal interphase P.
      aeruginosa (5.9 +/- 0.9 x 10(6) colony-forming units (cfu)) was pipetted onto the
      organ culture surface, and incubated for 15 min, 1, 2, 4, 8, 12, 16, and 24 h, at
      37 degrees C in 5% CO2 in a humidified atmosphere. Assessment has been made by
      transmission and scanning electron microscopy. Transmission electron microscopy
      (TEM) showed that uninfected organ cultures had normal ultrastructure. TEM of
      infected organ cultures at 8 h showed significant epithelial damage: 43.9 +/- 10%
      of cells extruding from the epithelial surface, 17.7 +/- 3% of cells with loss of
      cilia, 32.9 +/- 10.2% of cells with mitochondrial damage, and 11.6 +/- 3% of
      cells with cytoplasmic blebbing. P. aeruginosa only infrequently adhered to
      normal epithelium, but adhered to areas of epithelial damage and to basement
      membrane. Scanning electron microscopy (SEM) of organ cultures up to 2 h found P.
      aeruginosa only infrequently associated with mucus. SEM at 4 h revealed P.
      aeruginosa predominantly associated with mucus and extruded damaged epithelial
      cells, but also occasionally associated with cilia, and very occasionally with
      unciliated cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7828680
TI  - Pseudomonas aeruginosa exotoxin A induces pulmonary endothelial cytotoxicity:
      protection by dibutyryl-cAMP.
AB  - In pseudomonal septicaemia, serum levels of antibody to exotoxin A have been
      demonstrated to be an important independent predictor of survival. Previously, we
      have demonstrated that exotoxin A directly injures pulmonary endothelial cells,
      and that dibutyryl-cyclic adenosine monophosphate (Db-cAMP) can attenuate this
      injury. The object of this study was to examine the mechanisms of this pulmonary
      endothelial cell injury and the mechanism of Db-cAMP protection. The effects of
      differing duration of exposure to exotoxin A and a reduction in temperature on
      endothelial cell injury were examined. In addition, the effect of post-treatment
      with Db-cAMP on exotoxin A-induced endothelial cell injury was studied. A brief,
      5 min, exposure to exotoxin resulted in maximum injury comparable to that
      produced by 18 h exposure. This injury did not occur at low temperatures, which
      would inhibit receptor-mediated endocytosis. Db-cAMP protected endothelial cells,
      even when added up to one hour after exotoxin exposure. These results suggest
      that, in this model, exotoxin A-induced injury of endothelial cells is receptor
      mediated. Furthermore, this injury may be attenuated even after exotoxin A
      internalization has taken place.

PMID- 7828681
TI  - Bacterial adhesion to oropharyngeal and bronchial epithelial cells in smokers
      with chronic bronchitis and in healthy nonsmokers.
AB  - Bacterial adhesion is probably a prerequisite for colonization of mucous
      membranes, but adhesion to the bronchial mucosa has not been studied in detail.
      We investigated adhesion of respiratory pathogens to bronchial epithelial cells,
      and asked whether chronic bronchitis had an influence on bacterial adhesion.
      Oropharyngeal and bronchial cells were collected during bronchoscopy from 14
      healthy nonsmokers, 22 smokers with nonobstructive chronic bronchitis, and 19
      smokers with chronic bronchitis and chronic obstructive pulmonary disease (COPD).
      Patients with a forced expiratory volume in one second (FEV1) less than 50%
      predicted were excluded. Adhesion of highly adherent test strains of H.
      influenzae and S. pneumoniae to these cells were studied. The test strains of H.
      influenzae and S. pneumoniae were found to adhere well to both oropharyngeal and
      bronchial cells. H. influenzae showed a higher degree of adhesion both to
      ciliated and goblet cells from the patients with nonobstructive bronchitis than
      to cells from the healthy nonsmokers. No corresponding difference was found for
      S. pneumoniae. The patients with COPD did not differ from the controls in their
      adhesion values. Our results indicate that bacterial adhesion is of importance
      for the colonization and retention of H. influenzae in the human airways. For S.
      pneumoniae the role of adhesion is more uncertain.

PMID- 7828682
TI  - Natural evolution of sleep apnoea syndrome: a five year longitudinal study.
AB  - We wanted to investigate the natural evolution of Obstructive Sleep Apnoea
      Syndrome (OSAS). We therefore followed 58 patients who refused any treatment at
      the time of diagnosis. Of the eligible patients 32 subjects enrolled in
      instrumental follow-up. The effects on daytime somnolence, daytime lung function
      and nocturnal respiratory disturbances were retrospectively evaluated by
      repeating Multiple Sleep Latency Test (MSLT), spirometry and polysomnography
      after a follow-up period of at least 5 years (5.7 +/- 0.2 SEM yrs). In the
      patient group as a whole the mean Apnoea+Hypopnoea Index (AHI), the mean low
      arterial oxygen saturation (Sao2) and the mean Body Mass Index (BMI) did not
      change over time. The only significant differences were the increase in mean
      duration of apnoeas (21.0 vs 23.5 s) and hypopneas (13.5 vs 16.3 s) and the
      decrease in AHI < 80% (13.3 vs 7.9). No correlations were found between the
      changes in AHI or mean low Sao2 and age, BMI, AHI, mean low Sao2, pulmonary
      function tests or arterial blood gases at baseline. No significant changes were
      observed in systemic blood pressure, pulmonary function tests, blood gases
      analysis or MSLT. "Improved" (n = 6) and "worsened" (n = 7) groups were defined
      by a reduction or increase in AHI over 35% of baseline value. At baseline the
      "worsened" group tended to have lower AHI and higher mean low Sao2 compared with
      the "improved" group. In the "worsened" group the BMI rose significantly from
      26.0 to 29.2, AHI rose significantly from 14.1 to 51.3 and mean low Sao2
      decreased from 92 to 90 (NS).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7828683
TI  - Hand-scoring of MESAM 4 recordings is more accurate than automatic analysis in
      screening for obstructive sleep apnoea.
AB  - The MESAM 4 system, developed to monitor breathing sounds, heart rate, arterial
      oxygen saturation (Sao2) and body position, was proposed as a screening method
      for obstructive sleep apnoea (OSA). The aim of the study was to assess the
      accuracy of hand-scoring versus automatic-scoring in screening for obstructive
      sleep apnoea. The study population consisted of 56 patients, 51 males, and 5
      females, mean age 47 +/- 10 yrs, suspected of having obstructive sleep apnoea.
      Full polysomnography and MESAM 4 recordings were performed simultaneously. The
      apnoea+hypopnoea index was hand-scored in polysomnography and in MESAM 4. The
      hand-scoring in MESAM 4 was based on analysis of breathing sounds, heart rate and
      Sao2 changes taken together. The automatic-scoring system of MESAM 4 calculated
      oxygen desaturation index, heart rate variation index and intermittent snoring
      index. The diagnosis of obstructive sleep apnoea (apnoea+hypopnoea index > or =
      10) was established by polysomnography in 37 patients. Sensitivity and
      specificity of hand-scored MESAM 4 diagnosis were 100 and 63%, respectively.
      Sensitivity and specificity of MESAM 4 diagnosis with automatic-scoring were:
      from oxygen desaturation index 100 and 27%; from heart rate variation index 81
      and 74%; and from intermittent snoring index 92 and 16%, respectively. We suggest
      that hand-scoring of MESAM 4 is more accurate than automatic-scoring in screening
      for obstructive sleep apnoea.

PMID- 7828684
TI  - Required levels of nasal continuous positive airway pressure during treatment of
      obstructive sleep apnoea.
AB  - The improvement in the severity of obstructive sleep-related breathing disorders
      during nasal continuous positive airway pressure (NCPAP) therapy can account for
      the decrease in the required NCPAP level with time. The aim of this study was to
      prospectively quantify the changes in the required NCPAP level over time of use
      in sleep apnoea-hypopnoea syndrome (SAHS). Forty sleep apnoea-hypopnoea patients
      were evaluated before and during the time course of NCPAP therapy. The effective
      NCPAP level was defined as the positive pressure level that abolished apnoeic and
      hypopnoeic events and snoring in all sleep stages and sleep positions. This
      pressure level was determined within 2 weeks after baseline diagnostic sleep
      study. Sleep studies with NCPAP and NCPAP titration were performed after 2 (n =
      40), 8 (n = 40), and 20 (n = 24) months of NCPAP therapy. The initial effective
      NCPAP level was 9.6 +/- 0.4 cmH2O. It progressively decreased to 8.8 +/- 0.4, 7.9
      +/- 0.4 and 7.7 +/- 0.5 after 2, 8 and 20 months, respectively; the difference
      being significant between the first three NCPAP nights. There was a poor
      relationship between the changes in the effective NCPAP and changes in weight
      recorded at the different visits. There was a weak negative relationship between
      the changes in NCPAP and the previous NCPAP level. In 13 patients, the apnoea
      hypopnoea index (AHI) remained > 10 n.h-1 at the first NCPAP trial because the
      effective NCPAP level was not tolerated. Despite a suboptimal NCPAP level, their
      sleep architecture improved, and they all reported a subjective improvement in
      diurnal hypersomnolence.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7828685
TI  - Lung function, CT-scan and X-ray in upper airway obstruction due to thyroid
      goitre.
AB  - The purpose of this study was to assess the clinical reliability and to compare
      routine lung function tests (maximal flows and resistance) and radiological
      images (computed tomography (CT)-scan and X-ray) in upper airway obstruction. We,
      therefore, performed these examinations prospectively in 28 female patients (aged
      68 +/- 13 yrs) with a goitre and without pulmonary disorders. Lung function
      measurements consisted of maximum expiratory and inspiratory flow-volume curves
      and of airway resistance. CT-scans and X-rays were performed during apnoea at
      functional residual capacity (FRC). Peak expiratory flow was 3.6 +/- 1.3 l.s-1
      (i.e. 62 +/- 21% predicted); airway resistance was 0.38 +/- 0.14 kPa (i.e. 149 +/
      58% pred); and specific conductance was 1.0 +/- 0.3 kPa (i.e. 70 +/- 24% pred).
      Almost all lung function tests were significantly correlated with each other. On
      CT-scan the tracheal cross-sectional area at the zone of tracheal narrowing could
      be evaluated in 26 patients and was 58 +/- 17% (CT1/2) of the control area 2 cm
      above the carina (CT2). On X-ray the sagittal and coronal tracheal diameters at
      the zone of narrowing could only be measured in 16 subjects and were 60 +/- 17%
      (X-dia1/2) of the diameter at the control level. CT1/2 and X-dia1/2 were
      significantly correlated to each other. No correlation was found between the lung
      function tests and the radiological indices except airway resistance and CT2.
      Routine lung function and CT-scan do not provide comparable information on the
      degree of airway obstruction due to a goitre.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7828686
TI  - Comparison of cervical magnetic stimulation and bilateral percutaneous electrical
      stimulation of the phrenic nerves in normal subjects.
AB  - Cervical magnetic stimulation is a new technique for stimulating the phrenic
      nerves, and may offer an alternative to percutaneous electrical stimulation for
      assessing diaphragmatic strength in normal subjects and patients in whom
      electrical stimulation is technically difficult or poorly tolerated. We compared
      cervical magnetic stimulation with conventional supramaximal bilateral
      percutaneous electrical stimulation in nine normal subjects. We measured
      oesophageal pressure (Poes), gastric pressure (Pgas) and transdiaphragmatic
      pressure (Pdi). The maximal relaxation rate (MRR) was also measured. The mean
      magnetic twitch Pdi was 36.5 cmH2O (range 27-48 cmH2O), significantly larger than
      electrical twitch Pdi, mean 29.7 cmH2O (range 22-40 cmH2O). The difference in
      twitch Pdi was explained entirely by twitch Poes, and it is possible that the
      magnetic technique stimulates some of the nerves to the upper chest wall muscles
      as well as the phrenic nerves. We compared bilateral, rectified, integrated,
      diaphragm surface electromyographic (EMG) responses in three subjects and found
      results within 10% in each subject, indicating similar diaphragmatic activation.
      The within occasion coefficient of variation, i.e. same subject/same session, was
      6.7% both for magnetic and electrical twitch Pdi. The between occasion
      coefficient of variation, i.e. same subject/different days, was 6.6% for magnetic
      stimulation and 8.8% for electrical. There was no difference between relaxation
      rates measured with either technique. We conclude that magnetic stimulation is a
      reproducible and acceptable technique for stimulating the phrenic nerves, and
      that it provides a potentially useful alternative to conventional electrical
      stimulation as a nonvolitional test of diaphragm strength.

PMID- 7828687
TI  - Nutritional depletion in relation to respiratory and peripheral skeletal muscle
      function in out-patients with COPD.
AB  - Although increasing attention has been paid to nutritional aspects in chronic
      obstructive pulmonary disease (COPD), limited information is available regarding
      the prevalence and consequences of nutritional depletion in a random out-patient
      COPD population. We studied body composition in relation to respiratory and
      peripheral skeletal muscle function in 72 COPD patients (mean (SD) forced
      expiratory volume in one second (FEV1) 53 (15) % predicted), who came to the lung
      function laboratory for routine lung function measurements. Patients were
      characterized by the degree of body weight loss and fat-free mass depletion.
      According to this definition, 14% of the group suffered from both loss of body
      weight and depletion of fat-free mass, whereas 7% had one of these conditions. We
      found that tissue depletion was concomitant with lower values for respiratory and
      peripheral skeletal muscle strength (46.0 (27.2) vs 77.1 (29.8) kg), and a
      significantly lower transfer coefficient for carbon monoxide (KCO 64.9 (16.2) vs
      81.9 (24.5) % pred). Stratification by KCO (< 60% vs > 80%) also revealed
      significantly lower values for fat-free mass and higher values for intrathoracic
      gas volumes, total lung capacity (TLC) and residual volume (RV) in the group with
      a KCO < 60% pred. Analysis of covariance, taking fat-free mass as covariate,
      indicated an independent contribution of KCO on maximal inspiratory mouth
      pressure (PImax) but not on peripheral skeletal muscle strength. It is concluded
      that a substantial number of COPD out-patients suffer from nutritional depletion,
      preferentially affecting peripheral skeletal muscle function.

PMID- 7828688
TI  - Comparison of two epidemiological protocols for measuring airway responsiveness
      and allergic sensitivity in adults.
AB  - In recent years, airway responsiveness has commonly been measured in
      epidemiological studies using one of two methods. In one method, histamine is
      administered via a handheld DeVilbiss nebulizer and in the other, methacholine is
      administered via a dosimeter. Allergic sensitivity has commonly been measured by
      either the allergen droplet method or by Phazet. We wanted to assess the
      comparability of airway responsiveness and of allergic sensitivity measured by
      both methods. A total of 48 volunteers, including normal and asthmatic subjects,
      participated in the study. Subjects first underwent one of the two tests of
      airway responsiveness and allergic sensitivity, and then returned within 10 days
      to undergo tests using the second protocol. Commencement protocol was allocated
      in random order. There was good agreement between both methods for assessing
      airway responsiveness and for assessing allergic sensitivity. The difference for
      dose response ratio (DRR) between histamine and methacholine was a 1.19 (95% (CI)
      0.78, 1.82) fold changes, which was not statistically significant. Agreement
      between allergic sensitivity methods was perfect for Alternaria tenuis, good for
      rye-grass (kappa = 0.71) and moderate for cat and Dermatophagoides pteronyssinus
      (kappa approximately 0.5). It is possible to compare data from epidemiological
      studies which use these methods.

PMID- 7828689
TI  - Differences in airway responsiveness between children and adults living in the
      same environment: an epidemiological study in two regions of New South Wales.
AB  - The aim of the present study was to compare the severity of asthma in children
      and adults living in the same home environments. In winter 1991 and 1992, we
      studied two large random samples of children living in two different regions;
      and, three months later, we conducted a study of adults who lived with enrolled
      children. A total of 805 children and 814 adults attended in Lismore, and 850
      children and 711 adults in Wagga Wagga. Questionnaires were used to measure
      symptom history, histamine inhalation challenge to measure airway
      hyperresponsiveness (AHR) and skin-prick tests to measure allergy. There was a
      higher prevalence of asthma in children than in adults: recent wheeze was 1.5
      times higher; asthma medication use was 1.5 times higher; diagnosed asthma was
      1.6 times higher; and AHR was two times higher. Current asthma (AHR and recent
      wheeze) was 9.5-11.3% in children and 5.4-5.6% in adults. These differences were
      statistically significant. In both regions, airway responsiveness was more severe
      in children who were sensitized to common allergens than in similarly sensitized
      adults. These results suggests that airways can develop protective mechanisms
      with age, or that recent environmental changes in factors such as allergen
      levels, diet or treatment practices have led to immunological changes and to
      increased airway responsiveness in this generation of children.

PMID- 7828690
TI  - Distribution of peak expiratory flow variability by age, gender and smoking
      habits in a random population sample aged 20-70 yrs.
AB  - Peak expiratory flow (PEF) variability can be considered as an index of bronchial
      lability. Population studies on PEF variability are few. The purpose of the
      current paper is to describe the distribution of PEF variability in a random
      population sample of adults with a wide age range (20-70 yrs), and to assess
      relationships to age, gender and smoking habits. PEF data were collected in 511
      participants of the Dutch part of the European Community Respiratory Health
      Survey. A training effect was found, absolute PEF values on the first measurement
      day being significantly lower. Females had greater PEF variability (adjusted for
      age, height and pack-years) and lower absolute PEFs than males. The mean within
      day variation (amplitude % mean) was 3.66% (SD 2.03%), whereas the mean day-to
      day variation was relatively small: 0.08% (SD 1.53%). Absolute PEFs were lower
      and amplitude % mean were significantly higher in older age groups. Smoking was
      significantly associated with lower mean PEFs and greater amplitude % mean. We
      observed lower mean values of the amplitude % mean than other investigators,
      possibly related to lower frequency of PEF recording (twice daily). We conclude
      that PEF and PEF variability have a normal or log-normal distribution. When
      studying PEF variability, age, gender and smoking habits should be taken into
      account.

PMID- 7828691
TI  - The relationship of dietary fish intake to level of pulmonary function in the
      first National Health and Nutrition Survey (NHANES I)
AB  - Eicosapentaenoic acid (EPA), which predominates in marine fish, tends to
      counteract and inhibit the uptake and incorporation of arachidonic acid and
      membrane phospholipids and dilute arachidonic acid as a potential substrate for
      oxidation. Thus, fish intake may be protective for the occurrence of asthma and
      other pulmonary diseases. We wanted to examine the relationship between the
      effect of chronic dietary intake to fish and its relationship to level of
      pulmonary function. We performed this analysis using data from the First National
      Health and Nutritional Examination Survey (NHANES I). A detailed subsample of
      2,526 adults had a medical history questionnaire, that included a 24-hour dietary
      recall, and performed spirometric examination. Log of forced expiratory volume in
      one second (FEV1) served as a dependent variable in regression analysis which
      included an adjustment for height, age, cigarette smoking and gender. When added
      to the regression model including the above variables dietary fish intake showed
      a protective association with FEV1 (beta = 0.008 +/- 0.004, p = 0.028). When
      smokers were excluded from the analysis, the effect of fish intake on pulmonary
      function appeared to increase slightly (beta = 0.0108 +/- 0.006, p = 0.61). These
      data suggest that chronic dietary intake of fish is associated with higher levels
      of pulmonary function and is consistent with the hypothesis of an effect of fish
      oil on arachidonic acid metabolism.

PMID- 7828692
TI  - Time-limited protective effect of inhaled frusemide against aspirin-induced
      bronchoconstriction in aspirin-sensitive asthmatics.
AB  - Inhaled frusemide effectively prevents the bronchial obstructive response to
      allergens and to a number of nonallergic stimuli. In most of the experimental
      models in which it has been tested, the protective effect of frusemide has been
      evaluated for only a short time after administration. In aspirin-sensitive
      patients, acetylsalicylic acid causes an asthmatic reaction which typically lasts
      for 2 h or more after exposure. We investigated the presence and duration of the
      protective effect of inhaled frusemide against the bronchial response to aspirin
      in sensitive patients, using a specific inhalation challenge with lysine
      acetylsalicylate (LASA). In the first study, eight subjects with aspirin-asthma
      underwent two bronchial challenges with a single dose of lysine acetylsalicylate
      administered through a jet nebulizer, after treatment with 40 mg inhaled
      frusemide or placebo, according to a randomized, double-blind protocol. Forced
      expiratory volume in one second (FEV1) was monitored for 120 min after challenge.
      In the second study in eight patients, the protocol was modified by the use of a
      dosimeter for delivery of lysine acetylsalicylate, by reducing the dose of lysine
      acetylsalicylate to avoid intense reactions, and by extending the follow-up to 4
      h. In the first study, after placebo, FEV1 gradually decreased, reaching a
      maximum decrement of 39 +/- 3% at 120min. Inhaled frusemide exerted a significant
      protection at all time-points, although this activity appeared to decrease with
      time. In the second study, after placebo, inhaled lysine acetylsalicylate caused
      a gradual decrease in FEV1, which reached a maximum decrement at 180
      min.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7828693
TI  - Detection of early lung impairment with aerosol bolus dispersion.
AB  - The broadening of inhaled aerosol boluses (aerosol bolus dispersion) during
      respiration provides a noninvasive measure of convective gas mixing in the lungs.
      In this study, the sensitivity and specificity of this technique for the
      diagnosis of early lung impairment due to cigarette smoking was evaluated. Two
      hundred and sixteen randomly selected subjects (126 smokers and 90 nonsmokers)
      were investigated with aerosol dispersion in comparison to conventional lung
      function tests. The cumulative cigarette consumption of the subjects was
      quantified by "pack-years" (PY). Smokers were classified into the following
      groups: 0 < PY < or = 10; 10 < PY < or = 20; 20 < PY < or = 30; and PY > 30.
      Forced expiratory volume in one second (FEV1), maximal expiratory flow at 25, 50
      and 75% vital capacity (MEF25, MEF50 and MEF75) decreased significantly with
      increasing cigarette consumption. In comparison to nonsmokers, FEV1 was
      significantly reduced in smokers of 10 < PY < or = 30, and MEF75 was
      significantly reduced in smokers of PY > 20. Aerosol bolus dispersion increased
      with increasing PY. For all groups of smokers, even those with PY < 10, bolus
      dispersion was significantly increased in comparison to lifelong nonsmokers,
      indicating alterations in convective gas mixing in the lungs. Calculation of
      receiver operating characteristics for the lung function parameters under
      consideration showed that bolus dispersion has a higher sensitivity and
      specificity than conventional lung function parameters. Hence, the aerosol bolus
      dispersion test could be a promising epidemiological tool to study early
      abnormalities in intrapulmonary gas mixing due to environmental factors.

PMID- 7828694
TI  - Lung deposition of budesonide from Turbuhaler is twice that from a pressurized
      metered-dose inhaler P-MDI.
AB  - The pulmonary and systemic availability of budesonide after inhalation from a dry
      powder inhaler, Turbuhaler, and from a pressurized metered-dose inhaler (P-MDI)
      were compared in healthy volunteers. Two different methods were used to assess
      pulmonary availability: 1) calculated from the systemic availability corrected
      for an oral availability of 13% (n = 24); and 2) after blocking of
      gastrointestinal absorption by administration of a charcoal suspension (n = 13).
      An intravenous infusion of budesonide was used as a reference. The systemic
      availability of budesonide, calculated as a geometric mean and expressed as
      percentage of the metered dose, was 38% for Turbuhaler and 26% for P-MDI. The
      pulmonary availability, calculated using the first method, was 32% and 15% for
      Turbuhaler and P-MDI, respectively; and, using the second method, 32% and 18%,
      respectively. The results of the present study indicate that administration of
      budesonide via Turbuhaler gives rise to a lung deposition which is approximately
      twice that of a P-MDI, with less variability, but that systemic availability is
      only increased by approximately 50%. Thus, the present data suggest that by
      administrating budesonide via Turbuhaler, instead of a P-MDI, the same degree of
      asthma control can be achieved with a lower dose, which, in turn, reduces the
      risk of undesired systemic effects.

PMID- 7828695
TI  - Effect of inhaled budesonide on seasonal changes in sensitivity and maximal
      response to methacholine in pollen-sensitive asthmatic subjects.
AB  - The aim of this study was to investigate the effect of inhaled budesonide on
      modifications of the provocative concentration of agonist causing a 20% fall in
      forced expiratory volume in one second (FEV1) (PC20) and maximal response plateau
      to inhaled methacholine during the pollen season in pollen-sensitive subjects
      with mild asthma. The effects of inhaled budesonide (800 micrograms.day-1) on the
      threshold value (PC20) and maximal response plateau to inhaled methacholine were
      studied in 28 pollen-sensitive subjects with mild asthma during a pollen season
      in a randomized, double-blind, placebo-controlled parallel fashion. They were
      challenged with methacholine (up to 200 mg.ml-1) in February (preseasonal
      assessment) and during the middle of the pollen season (in May and again in
      June). Subjects treated with budesonide (n = 13) were protected from the decrease
      in PC20 seen in the placebo (n = 15) group (geometric mean PC20 placebo group:
      preseasonal = 8.51, May = 2.19 and June = 1.78 mg.ml-1; budesonide group:
      preseasonal = 3.71, May = 3.23 and June = 2.40 mg.ml-1; intergroup differences in
      doubling concentrations, p < 0.05). Among 10 subjects in the placebo group who
      reached plateau during the preseasonal assessment, seven lost the plateau in May
      and six in June. In the budesonide group, among seven subjects who reached
      plateau during the preseasonal assessment, three lost the plateau in May and four
      in June. Between-group differences were not significant. We conclude that in
      pollen-sensitive subjects with mild asthma, inhaled budesonide blocks the effects
      of natural allergen exposure on the methacholine threshold value.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7828696
TI  - Endobronchial presentation of Hodgkin's disease: a report of nine cases and
      review of the literature.
AB  - Although mediastinal involvement by Hodgkin's disease is frequent, the initial
      presentation of the lymphoma by an endobronchial lesion is rare. Therefore, the
      question of whether patients with Hodgkin's disease should undergo fibreoptic
      bronchoscopy as a staging procedure remains unresolved. In a series of 469
      patients with newly diagnosed Hodgkin's disease during a 10 year period, we
      reviewed the clinical features of nine patients who presented with an
      endobronchial tumour. They were compared to 34 previously published cases. The
      major presenting symptoms were cough, wheezing and haemoptysis. Bulky mediastinum
      was seen in six cases. The three other patients presented respiratory symptoms
      evocative of endoluminal invasion. All but one of the patients received combined
      modality therapy, as currently accepted for patients with poor prognostic
      factors. The overall actuarial survival was 74% after 4 yrs of follow-up. A
      selective subgroup of patients with stage I-II supradiaphragmatic and
      endobronchial Hodgkin's disease may, thus, present without poor prognostic
      factors (but generally with respiratory symptoms), and might be undertreated if
      this localization is not recognized. We propose that these patients should
      undergo fibreoptic bronchoscopy.

PMID- 7828697
TI  - Differential cytology of bronchoalveolar lavage fluid in normal children.
AB  - Bronchoalveolar lavage (BAL) is increasingly used in the assessment of pulmonary
      diseases in children. However, reference values for cellular and non-cellular
      constituents of BAL fluid in children are lacking. We have studied the
      differential cytology of BAL fluid in 48 children aged 3-16 years (mean age +/-
      SD 7.9 +/- 3.5 yrs) undergoing elective surgery for nonpulmonary illnesses. A
      flexible bronchoscope (Pentax 3.5 or 4.9 mm) was wedged in the middle lobe or one
      of its segments. BAL was performed with 3x1 ml-kg-1 body weight of normal saline
      warmed to body temperature. The first sample was studied separately; subsequent
      samples were pooled for analysis. The mean recovery was 58 +/- 15%. Significantly
      more granulocytes and less lymphocytes were found in the first, as compared to
      the pooled, sample. Total cell counts were highly variable and ranged from 0.5
      57.1 x 10(4) ml-1. Macrophages were the predominant cell type, with a mean
      percentage of 81.2 +/- 12.7%. The relative proportion of lymphocytes was higher
      than that reported in most studies of adult volunteers (16.1 +/- 2.4%). No age
      dependency was observed for either cell type. The mean percentage of granulocytes
      was 2.5 +/- 3.3%. Absolute granulocyte counts were significantly higher in
      children under 8 yrs of age. This study provides the first reference data on BAL
      differential cytology in children without pulmonary disease and will be the basis
      for future investigations of BAL in paediatric lung diseases.

PMID- 7828698
TI  - Inspiratory muscle testing in stable COPD patients.
AB  - Exploration of inspiratory muscles in stable chronic pulmonary disease patients
      can be important in the investigation of a respiratory handicap unsatisfactorily
      explained by alterations of the passive respiratory system, or in the follow-up
      of patients undergoing treatments that can interfere with muscle function.
      Compensatory mechanisms tend to counterbalance the deleterious effects of
      hyperinflation in these patients, and precise clinical data are needed in order
      to avoid mistakes due to underverified hypotheses. Investigation of inspiratory
      muscle function requires the study of output data under various states of
      activity of the system. As outputs, volume displacement lacks specificity,
      pressure measurements can be more specific but are at times invasive and should
      be associated with lung volume measurements, electromyography is methodologically
      complex, nonquantitative and of poor reproducibility. Voluntary manoeuvres depend
      upon subject co-operation, and do not allow partitioning of output between the
      action of different muscle groups. Transcutaneous electrical phrenic nerve
      stimulation is devoid of these inconveniences, but it explores only one muscle
      (the diaphragm) under conditions that are not "natural" (relaxed rib cage).
      Recently, perspectives for easier clinical assessment of inspiratory muscle
      function in chronic obstructive pulmonary disease patients have been opened by
      cervical magnetic stimulation, better understanding of the meaning of mouth
      pressure in relationship to phrenic stimulation, and development of noninvasive
      tests, such as nostril pressure during sniff or phonomyography. If validated,
      such tests should provide a reasonably limited panel of clinical tools to better
      appreciate muscle function in this setting.

PMID- 7828699
TI  - Exposure to environmental tobacco smoke and risk of lung cancer: the
      epidemiological evidence.
AB  - Exposure of nonsmokers to environmental tobacco smoke (ETS) is widespread in
      European countries, the most serious exposures occurring at home and in the
      workplace. Epidemiological studies available up to 1986 have been reviewed by
      several international and national authorities, which agreed in concluding that
      ETS exposure is causally related to lung cancer. A number of epidemiological
      studies have been published since then, and have confirmed this association. The
      possibility of positive results due to bias has been envisaged; it seems,
      however, that such bias could not explain the whole excess of lung cancer. Few
      data are available on confounders, such as diet and previous history of lung
      disease, that might be responsible for the association; however, there is no
      evidence that they play an important role. Moreover, the biological plausibility
      of a causal association is supported by the similarity of the composition of ETS
      and active smoke. The causal association between ETS exposure and lung cancer now
      seems well-established; however, its public health impact is still debated.
      Estimates are available from the United States, Canada, Australia, New Zealand
      and England.

PMID- 7828700
TI  - Implantable access system for prolonged intrapleural immunotherapy.
AB  - We describe our experience using an implantable Port-A-Cath access system for
      intrapleural administration of gamma-interferon (gamma-IFN) in malignant
      mesothelioma patients. Twenty nine patients, with histologically proven malignant
      mesotheliomas were included in this study. To avoid complications the device was
      implanted in a subcutaneous pocket, and the catheter was connected via a tunnel.
      Also, a suction drain was installed in the pocket after placement. This procedure
      greatly reduced the high infection rate (64%) encountered with conventional open
      chest tubes. Patients' tolerance was excellent and maintenance minimal. In our
      opinion, the Port-A-Cath system is the most suitable device for intra-cavitary
      long-term therapy of malignant pleural effusions.

PMID- 7828701
TI  - Bronchocentric granulomatosis and central diabetes insipidus successfully treated
      with corticosteroids.
AB  - Bronchocentric granulomatosis (BCG) is a rare chronic granulomatous lung disease
      that leads to destruction of the airway walls. It has been observed in
      association with various conditions, but never, so far, been reported to involve
      the central nervous system. We report a case of histologically confirmed
      pulmonary bronchocentric granulomatosis temporally associated with a partial
      central diabetes insipidus (CDI). Although the pathological basis of the
      posterior pituitary gland involvement was not ascertained, the temporal
      association of bronchocentric granulomatosis and central diabetes insipidus, as
      well as the fact that corticosteroid treatment provided stable remission of both
      conditions after a 10 month follow-up, strongly suggest that central diabetes
      insipidus was aetiologically related to bronchocentric granulomatosis in this
      patient.

PMID- 7828702
TI  - Severe inflammatory upper airway stenosis in ulcerative colitis.
AB  - Severe upper airway stenosis was diagnosed in a 23 year old woman who presented
      with hoarseness, cough and dyspnoea 8 yrs after initial diagnosis of ulcerative
      colitis. The respiratory symptoms worsened over the next few months, the patient
      eventually developing dysphagia and ultimately severe upper airway obstruction.
      The narrowest site was the glottis, which was severely stenosed by inflammatory
      swellings. Systemic corticosteroids led to rapid clinical improvement and
      restoration of normal airway patency within a few months. Ulcerative colitis is
      frequently associated with extraintestinal inflammatory manifestations. In the
      respiratory tract these usually take the form of chronic bronchitis, which
      occasionally develops into bronchiectasis. This case confirms that the
      inflammation can also involve the larynx and large airways.

PMID- 7828703
TI  - Endobronchial nocardiosis.
AB  - The presentation of a Nocardia infection is quite variable. We report a case of
      nocardiosis presenting as endobronchial obstruction with postobstructive
      pneumonia and atelectasis, in a patient with a low index of suspicion for
      bronchogenic carcinoma. Our report emphasizes the importance of considering the
      diagnosis of endobronchial nocardiosis in patients with endobronchial obstruction
      and a low index of suspicion for carcinoma, as well as those with a high index of
      suspicion, but with repeatedly negative biopsies.

PMID- 7828704
TI  - Trichomonas in pleural effusion.
AB  - Numerous living trichomonads were seen in a parapneumonic pleural effusion, in a
      patient who was at risk of aspiration pneumonia because of acute alcoholism. Of
      all the drugs administered, metronidazole had the most favourable therapeutic
      effect. However, decortication was necessary for the successful outcome.

PMID- 7828705
TI  - Challenging an exercise challenge protocol.

PMID- 7828706
TI  - Assessing reproducibility: agreement vs correlation.

PMID- 7828707
TI  - Creating a participant text: writing, multiple voices, narrative multiplicity.
AB  - This article uses the ideas of social constructionism to explore how families
      change by investigating the way our perceptions of ourselves in relation to
      others are formed through language. The idea that language has the inherent
      potential to generate a reply has strongly influenced our thinking. We propose
      that the reply to others is shaped by our initial reply to ourselves in inner
      conversation. Interaction moves back and forth from inner conversation to
      conversation with others, from monologue to dialogue, becoming the "stuff" of new
      narratives. The particular focus on language in this article is on how adding
      writing to the session conversation produces a "participant text," a therapeutic
      narrative that is composed of the voices of the family and the therapists. These
      voices, often newly discovered or invented, allow our narrative discourse to
      expand and multiply. Using this approach with individuals, couples, and families
      from different socioeconomic levels, we have worked with mourning, divorcing
      couples, recovery from abuse, marital conflict, parenting dilemmas, and physical
      illness.

PMID- 7828708
TI  - Using a narrative metaphor: implications for theory and clinical practice.
AB  - The evolution of family therapy from a cybernetic metaphor to a narrative
      metaphor has led us to think differently about therapy, about clients, and about
      ourselves as therapists. In this article we pursue how this different way of
      thinking has informed a theoretical understanding of a narrative therapy approach
      and consequently has opened space for different ways of working clinically. We
      begin by tracing the evolution to narrative; we consider the implications of
      social constructionism and its political effects; and we complete the discussion
      by focusing on narrative theory. We then show how the clinical work follows
      logically and is coherent with the theoretical considerations. We describe, and
      illustrate with clinical examples, an innovative approach to working with couples
      and families with adolescents. In this work we pay attention to the larger
      cultural stories, including gender constructions, and to personal stories that
      persons have created to make meaning out of their experience as they interact
      with one another in a reciprocal meaning-making process. Interventions focus on
      externalizing the problem narrative that is influencing the client(s), mapping
      the effects of the problem pattern and/or the totalizing view persons might have
      of others, and creating space for client(s) to notice preferred actions and
      intentions. Finally, we close the loop by asking questions of ourselves and
      others about the effects of working from a narrative metaphor.

PMID- 7828709
TI  - Therapy with refugee families: what is a "good" conversation?
AB  - This article addresses the question of what is a "good" conversation by analyzing
      "poor" conversations. During a project on family therapy with refugee families,
      we often experienced what we labeled as "poor" conversations. We present examples
      of a variety of such conversations, which we then analyze with reference to
      therapeutic maps and central concerns of the therapists. We describe four
      patterns of therapist/client relationships that emerged from this analysis. The
      main focus of our discussion is to clarify when "poor" conversations may be an
      important part of the therapeutic process, and when and how they should be
      avoided. We believe that the issues we raise are central to therapeutic work in
      general and not just to therapy with refugee families.

PMID- 7828710
TI  - Treating the sexually abused child: a recursive, multimodal program.
AB  - This article describes a recursive, multimodal therapy approach for children who
      have been sexually abused by members of their family. The different therapeutic
      modalities (family, group, and individual) are conceived of as different
      "communities" that provide a variety of relationships, information, and
      perspectives on the incest experience. The child's involvement in these different
      communities allows her or him to develop a multiplicity of self-accounts. Meaning
      is further expanded through the recursive transfer of material across modalities.
      By determining the content that is discussed in any particular session, and by
      participating actively in decisions about transferring material across
      modalities, the child both develops an enhanced sense of personal agency and a
      connection to trustworthy family members. This approach is designed to allow each
      child's unique experience with incest to emerge. Clinical examples are provided,
      along with a description of the program that provides the setting for our
      multimodal approach to incest.

PMID- 7828711
TI  - The divine triangle: God in the marital system of religious couples.
AB  - Incorporating both Bowenian and structural approaches, this article offers a
      constructivist view for dealing with religious belief systems of couples. After
      exploring the evolving process by which couples mutually define an ongoing
      triadic relationship with their Deity, different triangular processes from an
      integrated structural and Bowenian perspective are presented. This view is
      evaluative in terms of the triangulation process rather than the belief systems
      themselves, and, as such, it can be useful in marital therapy regardless of the
      religious beliefs of the therapist. Implications for marital therapy are
      examined.

PMID- 7828712
TI  - Levels of meaning in family stress theory.
AB  - Major stressful life events, particularly those that have chronic hardships,
      create a crisis for families that often leads to reorganization in the family's
      style of functioning. A major factor in this reorganization is the meaning the
      family gives to the stressful event. Often the meaning extends beyond the event
      itself and leads to a changed view of the family system and even to a changed
      view of the world. Building on other family stress models, we elaborate the
      family's definition of the stressor into three levels of family meanings: (1)
      situational meanings, (2) family identity, and (3) family world view. Examples
      from clinical work and studies of families adapting to chronic illness are used
      to illustrate the relationship between these three levels of meaning,
      particularly as they change in response to crisis. Implications for clinical and
      empirical work are discussed.

PMID- 7828713
TI  - Alzheimer's disease: the impact of the family on spouses, offspring, and inlaws.
AB  - This article reports the findings from a study designed to identify qualities of
      the multigeneration family system that affected the relationship between the
      demands of Alzheimer's disease on the family and the health and well-being of (a)
      spouses, (b) offspring, and (c) offspring's spouses or "inlaws." Members of 97
      families of patients with Alzheimer's disease, recruited from four University
      affiliated Alzheimer's Centers, completed detailed questionnaires and
      participated in a 45-minute telephone interview to assess care-strain, personal
      stress, appraisals of three major domains of family life (World View,
      Structure/Organization, and Emotion Management), and three health and well-being
      indices (Anxiety/Depression, Somatic Symptoms, and Well-Being). Multivariate
      multiple regression equations, run separately for each of the three groups of
      family respondents and each of the three family domains, indicated: (1) no
      significant associations between the severity of the elder's disease and family
      member health and well-being; (2) female family members reported poorer health
      and well-being than male family members; and (3) caregiver strain was negatively
      associated with family member health and well-being. Further, appraised family
      qualities were associated with the health and well-being of the three groups of
      respondents differently: directly for offspring, interactively with severity of
      patient disorder for inlaws, and not at all for spouses. The data suggested that
      some family qualities served a protective function, whereas others exacerbated
      the negative effects of caregiving by affecting personal health and well-being.
      The findings are interpreted in terms of the different roles and expectations for
      care-giving placed on spouses, offspring, and inlaws. It is suggested that
      programs of intervention for patients with Alzheimer's and other chronic diseases
      should focus on the multigeneration family as the context for care, rather than
      only on the primary caregiver.

PMID- 7828714
TI  - Family perceptions of living with Alzheimer's disease.
AB  - The purpose of this study was to identify the major themes that 38
      multigenerational families emphasized in their conversations about living with
      Alzheimer's disease. Interviews were conducted with families that were providing
      home care in the early stages of the disease. Family perceptions were analyzed
      with the aid of a computer content analysis program. Families emphasized four
      themes: (a) the awareness that something was "wrong"; (b) the uncertain nature of
      the diagnosis; (c) excluding a family member; and (d) the ambiguous nature of
      family life with Alzheimer's disease.

PMID- 7828715
TI  - Sculpting present and future: a systemic intervention model applied to
      psychosomatic families.
AB  - We present a therapeutic intervention model for use with psychosomatic families.
      This method, the result of our extensive research on various psychosomatic
      disorders, uses family sculptures of the "present" and "future": each family
      member is requested to represent the family as it now "is," and how it "will be"
      in the future. We discuss the theoretical reasons for our choice of this method:
      (a) the opportunity to use a therapeutic language that is similar to the
      nonverbal language of the psychosomatic symptom, and (b) the usefulness of
      reinserting temporal dimensions into family systems that seem to have lost their
      evolutionary potential and to be in a sort of "time lock." Two clinical cases are
      discussed (a child with chronic asthma and an anorexic adolescent); the use of
      sculptures in both cases revealed the underlying problems and made positive
      therapeutic interventions possible. Finally, we point out how the use of
      sculpture as a therapeutic technique enables therapists to deal with multiple
      systemic levels.

PMID- 7828716
TI  - Irreverent thoughts about dialogue.

PMID- 7828717
TI  - Down-regulation of phospholipase C-gamma 1 during the differentiation of U937
      cells.
AB  - Phospholipase C (PLC)-gamma 1 and -gamma 2 play a pivotal role in signal
      transduction for cell proliferation and differentiation. The enzyme activity and
      protein level of PLC-gamma 1 were markedly decreased in the human histiocytic
      leukemia U937 cell line during the differentiation process which is induced by
      phorbol 12-myristate 13-acetate (PMA) but those of PLC-gamma 2 were not altered.
      Northern blot analysis showed that the levels of PLC-gamma 1 and -gamma 2
      transcripts were not changed. These results suggest that the expression of PLC
      gamma 1 during the PMA-induced differentiation may be down-regulated by post
      transcriptional processing.

PMID- 7828718
TI  - Stimulation of transforming growth factor-beta 1 transcription by cyclosporine.
AB  - In searching for a candidate mechanism for the immunosuppressive as well as
      fibrogenic consequences of cyclosporine usage, we have explored the hypothesis
      that cyclosporine stimulates transcription of transforming growth factor-beta 1
      (TGF-beta 1), a multifunctional cytokine endowed with immunosuppressive and
      fibrogenic properties. Our results demonstrate that cyclosporine (i) stimulates
      TGF-beta 1 promoter-dependent transcription of chloramphenicol acetyl transferase
      gene in transiently transfected human A-549 cells, (ii) stimulates the synthesis
      of TGF-beta 1 RNA transcripts in human T cells, and (iii) permits the
      expression/emergence of DNA regulatory proteins (retinoblastoma control factor-1
      (RCF-1) and RCF-2) that bind and regulate TGF-beta 1 promoter activity. Our
      studies demonstrate for the first time that cyclosporine stimulates TGF-beta 1
      gene transcription and suggest a novel mechanism of action of cyclosporine.

PMID- 7828719
TI  - A mitochondrial elongation factor-like protein is over-expressed in tumours and
      differentially expressed in normal tissues.
AB  - The tissue-specific expression of an antigen (P43) ubiquitously expressed at high
      levels in a variety of tumours of human and animal origin was investigated using
      a monoclonal antibody to P43. Whereas low amounts of P43 are expressed in the
      spleen, skeletal muscle and pancreas, P43 is abundantly produced in the liver and
      in other tissues such as the kidney, heart and brain which have levels of
      oxidative metabolism. Interestingly, a related protein of higher molecular weight
      is abundantly expressed in the lung and in amounts which were higher than those
      observed with other tissues. The human cDNA for P43 was isolated from a human
      liver cDNA library and mapped to chromosome 16 between p11.2 and 12 and also to a
      position near the centromere on the long arm of chromosome 17. The deduced amino
      acid sequence of P43 is remarkably similar to that of E. coli EF-Tu and the
      mitochondrial EF-Tu of S. cerevisiae with the structurally and functionally
      important amino acids of EF-Tu being completely conserved in P43. A comparison of
      the distribution of P43 and a mitochondrial protein Hsp 60 among different
      cellular fractions indicated a likely mitochondrial localisation for P43. Taken
      together these results suggest that P43 is a human mitochondrial elongation
      factor.

PMID- 7828720
TI  - Chaos in DNA partition during the last mitoses of the proliferative life-span of
      human fibroblasts.
AB  - We have followed with autoradiography the course of DNA synthesis and with
      cytofluorometry the partition of DNA during mitosis, through the different phases
      of the life-span of human fibroblasts. Towards the end of the proliferative
      potential of the cell population, DNA synthesis was disturbed during the late
      part of the S period. The DNA content of metaphases and of anaphases had a normal
      Gaussian distribution during the whole proliferative life-span of the cell
      population. At the very end, however, when cells entered the post-mitotic phase,
      the distribution of DNA content deviated from the normal Gaussian probability,
      becoming significantly skewed.

PMID- 7828721
TI  - Antibody characterisation of two distinct conformations of the chaperonin
      containing TCP-1 from mouse testis.
AB  - We describe a panel of antibodies specific to individual subunits of the
      chaperonin-containing TCP-1 (CCT) and one antibody that reacts with all the
      subunits of CCT. Immunoblot analysis of CCT purified from mouse testis suggests
      that the testis-specific subunit, S6, may be related to CCT zeta and that a co
      purifying 63 kDa protein may be a novel subunit of CCT. Using these antibodies in
      the analysis of CCT subjected to nondenaturing IEF we observed the resolution of
      two distinct conformations of CCT, which differ in their susceptibility to
      proteolysis and in the number of associated polypeptides.

PMID- 7828722
TI  - NMR and circular dichroism studies of synthetic peptides derived from the third
      intracellular loop of the beta-adrenoceptor.
AB  - The C-terminal part of the third intracellular loop of the beta-adrenoceptor is
      capable of stimulating adenylate cyclase in the presence of phospholipid vesicles
      via the stimulatory guanine nucleotide binding protein (Gs) [Palm et al. (1989)
      FEBS Lett. 254, 89-93]. We have investigated the structure of synthetic peptides
      corresponding to residues 284-295 of the turkey erythrocyte adrenoceptor in
      micelles, trifluoroethanol and aqueous solution, by using 2D 1H NMR and CD. In
      the presence of phospholipid micelles the peptides display a C-terminal alpha
      helical region, whereas the N-terminal part was found to be highly flexible.

PMID- 7828723
TI  - Nuclear factors specifically favor thyroid hormone binding to c-ErbA alpha 1
      protein (thyroid hormone receptor alpha) over-expressed in E. coli.
AB  - A recombinant rat thyroid hormone receptor alpha (TR alpha or c-ErbA alpha 1) was
      produced in E. coli as a non-mutated, nonfusioned protein and obtained as an
      efficient DNA and T3 binding protein that could be easily handled in a buffer
      soluble state (rec-TR alpha). It was found that nuclear extracts (NE) added to
      rec-TR alpha markedly amplified not only DNA binding, which has been well
      documented, but also T3 binding (increased binding site concentration), which has
      not yet been reported. This T3 binding amplifying effect on rec-TR alpha occurs
      at low NE protein concentrations that produce no or minimal endogenous TR with
      respect to rec-TR, while similar concentrations of other proteins (e.g. ovalbumin
      or cytosol) only moderately enhanced T3 binding. The T3 binding amplifying
      nuclear factors, which are partly heat-labile, appeared as necessary auxiliaries
      in the analyses of partially purified rec-TR alpha. A protective effect of NE
      against a loss of affinity for T3 under the action of antibodies directed to
      certain sequences in the TR alpha D domain suggests that nuclear factors help rec
      TR alpha to acquire and/or stabilize a conformation that allows the high affinity
      T3 binding. The nature of this nuclear amplifying factor is still unknown: RXR
      alpha which, produced in vitro, could amplify binding of the rec-TR alpha to a
      DNA thyroid response element, was unable to display such a rescue of high
      affinity binding sites.

PMID- 7828724
TI  - ATP synthase: activating versus catalytic proton transfer.
AB  - ATP synthase (F-ATPase) of chloroplasts, CF0CF1, is both activated and driven by
      transmembrane protonmotive force. We dichotomized between activating and driving
      proton transfer by specific inhibitors, tentoxin and venturicidin. Thylakoids
      membranes were submitted to voltage steps (by flashing light) superimposed to a
      steady pH-difference. Transient proton intake, transfer and release by CF0CF1 was
      monitored by spectroscopic probes. Both activities, activation and catalysis,
      required all three partial reactions of the proton, however, activating proton
      transfer rose first (monophasically, tau 1/2 approximately 15 ms) followed by
      another phase of equal magnitude with a time lag of about 15 ms. Both types of
      consecutive proton transfer reactions contribute free energy for ATP synthesis.

PMID- 7828725
TI  - Inhibition of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine metabolic activity of
      porcine FAD-containing monooxygenase by selective monoamine oxidase-B inhibitors.
AB  - The MPTP metabolic activity of porcine FAD-containing monooxygenase (FMO) (EC
      1.14.13.8) was inhibited considerably by deprenyl and pargyline, selective MAO-B
      inhibitors, and they showed typical competitive inhibition. Deprenyl and
      pargyline, amine derivatives were also examined as to whether they are substrates
      for the FMO. It was found that deprenyl and pargyline are excellent substrates
      for the FMO. The Ki and Km values of deprenyl and pargyline for the FMO are 14
      microM and 9 microM, and 14.3 microM and 11.6 microM, at pH 8.0 and 25 degrees C,
      respectively.

PMID- 7828726
TI  - Changes in ascorbate peroxidase activities during fruit ripening in Capsicum
      annum.
AB  - The ascorbate peroxidase (APX) system was studied in Capsicum annum during fruit
      ripening. A large increase in organelle APX activity was found during chloroplast
      chromoplast transition whereas only a slight difference was detected in total
      fruit extracts. On native gels, four different isoforms were found in total fruit
      extracts but the patterns for red and green fruit were quite different. In
      isolated organelles, six isozymes were found and a comparison of the patterns
      showed significant differences. A cDNA encoding a cytosolic APX was cloned and
      sequenced. The corresponding transcript was shown to increase 3-4-fold during
      fruit ripening.

PMID- 7828727
TI  - The rsp5-domain is shared by proteins of diverse functions.
AB  - A novel, unusually small, and highly conserved domain of modular intracellular
      proteins is described. The domain was first recognized as three repeats in the
      yeast rsp5 gene product and named thereafter. The rsp5 protein is thought to
      interact with nuclear proteins but also contains a C2 domain typical for
      cytoplasmic proteins. Further analyses revealed several additional occurrences of
      this domain in diverse protein classes, including cytoplasmic signal transduction
      proteins, gene products interacting with the transcription machinery, structural
      proteins like dystrophin, and a putative RNA helicase.

PMID- 7828728
TI  - Interaction between hsp70 and hsp40, eukaryotic homologues of DnaK and DnaJ, in
      human cells expressing mutant-type p53.
AB  - We have recently identified a novel 40-kDa heatshock protein hsp40 as a mammalian
      homologue of bacterial DnaJ protein. Here we demonstrate the physical interaction
      between hsp70 (DnaK homologue) and hsp40 in human cells as determined by
      immunoprecipitation methods. Co-immunoprecipitation of hsp70 with hsp40 was
      dependent on the presence of ATP or unfolded protein (reduced carboxymethylated
      alpha-lactalbumin). A mutant type of tumor suppressor gene product, mtp53, was co
      immunoprecipitated not only with hsp70 but also with hsp40. These results suggest
      the existence of a hsp70(DnaK)/hsp40(DnaJ) chaperone system in mammalian cells.

PMID- 7828729
TI  - Identification of two cell cycle regulated genes affecting the beta 1,3-glucan
      content of cell walls in Saccharomyces cerevisiae.
AB  - The Calcofluor white-hypersensitive mutants cwh52 and cwh53 are severely reduced
      in beta 1,3-glucan. CWH52 was equivalent to GAS1. CWH53 represented a new gene,
      located on the right arm of chromosome XII, and predicted to encode a 215 kDa
      protein with multiple transmembrane domains. The transcription of CWH53 was cell
      cycle-dependent and, similar to GAS1/CWH52, increased in late G1, indicating that
      the formation of beta-glucan is cell cycle-regulated. Further, in some mutant
      alleles of both gas1/cwh52 and cwh53 lethal concentrations of Calcofluor induced
      growth arrest at a specific phase of the cell cycle.

PMID- 7828730
TI  - Activation of an Asp-124-->Asn mutant of haloalkane dehalogenase by hydrolytic
      deamidation of asparagine.
AB  - Haloalkane dehalogenase hydrolyses various 1-halo-n-alkanes to the corresponding
      alcohols by covalent catalysis with formation of an alkyl-enzyme intermediate.
      The carboxylate function of the nucleophilic aspartate (Asp-124) that displaces
      the halogen during formation of the intermediate was changed to an amide by site
      directed mutagenesis (Asp-124-->Asn). Activity measurements and analysis of
      peptides containing the nucleophilic residue showed that the mutant enzyme was
      inactive, but that the activity increased by rapid deamidation of the asparagine
      residue, yielding wild type enzyme. There was no indication for isoaspartate
      formation during this process. The results suggest that a water molecule that is
      located close to the carboxyl function of Asp-124 in the X-ray structure is
      highly reactive and is responsible for the observed deamidation.

PMID- 7828731
TI  - Oxidized low-density lipoprotein is cytotoxic to human monocyte-macrophages:
      protection with lipophilic antioxidants.
AB  - Human monocyte-macrophages were incubated for 24 h with low-density lipoprotein
      (LDL) which had been previously oxidized for varying periods up to 24 h with
      copper ions, in the presence or absence of DL-alpha-tocopherol or probucol. The
      release of radioactivity from cells preloaded with tritiated adenine was used as
      an assay of toxicity. Toxicity of oxidized LDL increased with duration of copper
      oxidation and with increasing evidence of lipid oxidation, measured by assay of
      thiobarbituric acid-reactive substances and by gas chromatography. Oxidation and
      toxicity were inhibited by DL-alpha-tocopherol (200 microM) and probucol (50
      microM).

PMID- 7828732
TI  - The termini of a new citrus viroid contain duplications of the central conserved
      regions from two viroid groups.
AB  - A citrus viroid associated with dwarfing, CVdIIIA, has been sequenced and its 294
      nucleotide residues can be arranged to form the typical rod-like secondary
      structure of other viroids with 71% of nucleotides base-paired. CVdIIIA has
      greatest sequence similarity with apple scar skin viroid (ASSVd; 69%) and has the
      central sequence which is conserved in the ASSVd group. CVdIIIA is the smallest
      member of the ASSVd group but contains the terminal conserved region shared by
      all viroids over 300 nucleotides. The two ends of CVdIIIA are highly unusual in
      that each end appears to be derived from the conserved central core region of a
      different viroid group.

PMID- 7828733
TI  - The assembly state of the intermediate filament proteins desmin and glial
      fibrillary acidic protein at low ionic strength.
AB  - The low ionic strength structures of the type III intermediate filament (IF)
      proteins desmin and glial fibrillary acidic protein (GFAP) have been studied by
      transient electric birefringence measurements. Flexible dimers with a length of
      around 45 nm, particles with a length of 68 +/- 6 nm (presumably tetramers and
      hexamers) and larger aggregates of 108 +/- 19 nm are found. GFAP has an increased
      tendency to aggregate upon lowering of the pH. The aggregation state of desmin
      does not change in the pH range studied. The results are compared with previous
      results on vimentin.

PMID- 7828734
TI  - The second zinc atom in the matrix metalloproteinase catalytic domain is absent
      in the full-length enzymes: a possible role for the C-terminal domain.
AB  - Domain deletion mutants of the matrix metalloproteinases consisting of the
      catalytic domain only contain two zinc atoms per molecule. One is essential for
      catalysis, while the other may fulfil a structural role. We have analysed the
      zinc contents of both the full-length and the truncated mutants of prostromelysin
      1 and progelatinase A and report that the second zinc atom is not present in the
      full-length form of the proenzymes. Thus it seems likely that the role proposed
      for this zinc atom in maintaining the structure of the enzyme catalytic domain is
      performed by the C-terminal domain in the full-length enzyme.

PMID- 7828735
TI  - The KH module has an alpha beta fold.
AB  - The KH module has recently been identified in a number of RNA associated proteins
      including vigilin and FMR1, a protein implicated in the fragile X syndrome. In
      this work, NMR spectroscopy was used to determine the secondary structure in
      solution of a KH domain (repeat 5 from vigilin). Almost complete assignments were
      obtained for the 1H and 15N resonances using uniform 15N-labeling of the protein
      combined with homo-nuclear 2D 1HNMR and 3D 15N correlated 1H NMR. On the basis of
      NOE patterns, secondary chemical shifts and amide solvent exposure, the secondary
      structure consists of an antiparallel three stranded beta sheet connected by two
      helical regions. This domain may also be stabilized by an appended C-terminal
      helix which is common to many but not all members of the KH family.

PMID- 7828736
TI  - Two genes that encode ribosomal-protein S6 kinase homologs are induced by cold or
      salinity stress in Arabidopsis thaliana.
AB  - We have isolated two closely related cDNA clones (cATPK19 and cATPK6) with
      homology to protein-serine/threonine kinases from Arabidopsis thaliana using the
      polymerase chain reaction (PCR). The deduced amino acid sequences of the ATPK19
      and ATPK6 contain all 11 conserved regions of the catalytic domain of protein
      kinases, and have homology to p70 ribosomal S6 kinases (52%). ATPK19 and ATPK6
      have putative PEST regions in their N- and C-terminal regions, and these regions
      also contain putative phosphorylation sites that are recognized by casein kinases
      or proline-directed protein kinases such as cdc2, MAP kinase, and p54 MAP-2
      kinase (SAPK). The transcription levels of the ATPK19 and ATPK6 genes rapidly and
      markedly increased when plants were subjected to cold or high-salt stresses.
      These observations suggest that ATPK19 and ATPK6 may function in the adaptation
      of plant cells to cold or high-salt conditions, providing an understanding of the
      role of protein phosphorylation in plant responses to environmental stresses.

PMID- 7828737
TI  - Structure of three Kdn-containing oligosaccharide-alditols released from oviducal
      secretions of Ambystoma tigrinum: characterization of the carbohydrate sequence
      Fuc (alpha 1-5) [Fuc (alpha 1-4)] Kdn (alpha 2-3/6).
AB  - Oligosaccharide-alditols released by reductive beta-elimination from the egg
      jelly coat of Ambystoma tigrinum were analyzed by 1H NMR spectroscopy. As
      observed for five other amphibian species, these carbohydrate chains are highly
      species-specific, and should support the species-specificity of gamete
      interaction. The carbohydrate chains of Ambystoma tigrinum are characterized by
      the presence of a new type of sequence: Fuc (alpha 1-5) [(Fuc (alpha 1-4)] Kdn
      (alpha 2-3/6).

PMID- 7828738
TI  - Induction of apoptotic DNA fragmentation and cell death by natural ceramide.
AB  - We have found that a solvent mixture of ethanol and dodecane was able to disperse
      natural ceramide (Cer) into aqueous solution. In U937 cells, addition of natural
      Cer to medium caused a characteristic pattern of DNA fragmentation, which is
      indistinguishable from that caused by TNF alpha. The effective concentration of
      Cer is as low as 25 nM. The present study provides direct evidence that natural
      Cer functions as a second messenger mediating TNF alpha-induced DNA
      fragmentation. The use of this solvent to deliver hydrophobic natural Cer to
      cells will contribute to the elucidation of the biological function of Cer.

PMID- 7828739
TI  - Fibrodysplastic disease of the renal arteries.

PMID- 7828740
TI  - Vascular surgery in the United Kingdom.

PMID- 7828741
TI  - Cryopreserved vein homografts for arterial reconstruction.

PMID- 7828742
TI  - Assessment of inhomogeneities in elastic properties of in situ and reversed
      saphenous vein grafts in humans.
AB  - The elastic properties of newly implanted in situ (IS, n = 11) and reversed (RV,
      n = 21) saphenous grafts were studied with the use of Vessel Wall Doppler
      Tracking. From diameter, diameter change and simultaneously recorded pulse
      pressure, distensibility coefficient (DC) representing the intrinsic elastic
      properties and compliance coefficient (CC), a parameter of haemodynamic capacity,
      were calculated. In order to obtain a mechanical profile, the parameters were
      assessed at defined sites down the graft and native arterial system. In the RV
      group the reversal of the grafts resulted in a difference in diameter around the
      proximal anastomoses (7.4 vs. 4.3 mm, p < 0.01) and from proximal to distal (4.3
      vs. 5.9 mm, p < 0.01) in the grafts; around the distal anastomoses no differences
      in diameter were observed. Due to the natural taper of the in situ grafts,
      diameter decreased from proximal to distal in the grafts (4.5 vs. 3.2 mm, p <
      0.05) and no size differences were found around the anastomoses. In the RV group
      a decrease in DC was observed from proximal to distal in the grafts; whereas in
      the IS group no change in DC was found from proximal to distal in the grafts but
      a decrease in DC was observed around the distal anastomoses. In the RV group, a
      decrease in CC at the proximal anastomoses was observed (0.25 vs. 0.09 mm2/kPa, p
      < 0.01). In the IS group no change in CC was observed around the proximal
      anastomoses and distal anastomoses.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7828743
TI  - The effect of internal carotid artery elongation on intracranial blood flow.
AB  - Redundant length of the cervical part of the internal carotid artery (ICA) is a
      clear angiographic entity although the clinical significance is uncertain.
      Transcranial Doppler sonography (TCD) examinations were performed on 15 patients
      with 23 elongated ICAs. The recordings were obtained with the use of flat 2 MHz
      probe from the middle cerebral artery (MCA) and the intracranial part of ICA at
      rest and in eight possible extreme positions of head and neck rotation. The mean
      blood flow velocity in the intracranial part of the ICA obtained in the neutral
      position was 50.1 +/- 8.3 cm s-1 and after head and neck rotations was 49.8 +/-
      9.5 cm s-1. The mean blood flow velocity in the MCA was 55.8 +/- 6.7 cm s-1 and
      did not change significantly after head and neck movements (54.9 +/- 7.6 cm s-1).
      Analysis of 368 one minute recordings from all possible head positions showed no
      significant changes of blood flow velocity. Rotation of the head and neck has no
      significant influence on intracranial blood flow velocity in the presence of
      carotid artery elongation.

PMID- 7828744
TI  - The influence of arterial reconstructive surgery on the outcome of critical leg
      ischaemia.
AB  - OBJECTIVES: To analyse the effect of an aggressive vascular reconstruction policy
      on the outcome of critical leg ischaemia in a defined population. DESIGN: A
      retrospective survey of surgical in-hospital patient data related to population
      data in the study region over 22 years (1970-1991). SETTING: Vasa Central
      Hospital district in Western Finland. The area is served by one Central Hospital
      and two District Hospitals. MATERIALS: The population of 165,000 at the beginning
      of the study and 178,000 at the end of the study needing 977 interventions for
      chronic critical leg ischemia (CLI), 397 for acute ischaemia and 313 for
      noncritical leg ischemia. CHIEF OUTCOME MEASURES: Total and age-group related
      major amputation rates, mortality, rates of arterial interventions, limb salvage
      rate. MAIN RESULTS: The population > 65 years of age increased by 50% from 1970
      to 1991. Major amputation rates increased 2.5 times from 1970 to 1981. The mean
      age at amputation increased from 71 to 78 years and at reconstruction from 68 to
      74 years. The increase in numbers of reconstructions for CLI by 100% from 1980
      onwards was associated with a reduction in amputation rate by 60% from 1983 to
      1991. The 1- and 5-year survival rate after amputation was 55 and 20% and after
      reconstruction 83 and 45%. After reconstruction 1-, 3- and 5-year limb salvage
      rates were 83, 78 and 77% and limb salvage until death was 74%. CONCLUSIONS: With
      an aggressive reconstruction policy in CLI it is possible to reduce amputation
      rates with a reasonable mortality and morbidity even in patients in the 8th and
      9th decade of life.

PMID- 7828745
TI  - Loss of seeded endothelial cells in vivo. A study of Dacron grafts under
      different flow conditions.
AB  - OBJECTIVES: To assess, in vivo, the loss of endothelial cells seeded in a Dacron
      graft at low, restricted arterial flow and at normal unrestricted flow. DESIGN
      AND SETTING: Laboratory animal study. MATERIALS: Indium-111-oxine labelled
      endothelial cells were seeded in externally supported, preclotted Dacron grafts,
      inserted as interposition grafts in the carotid arteries of nine sheep. Activity
      (radioactivity) was measured, flow established, on one side unrestricted 120-180
      ml/minute, and on the other restricted to 50 ml/minute by a distal clamp. OUTCOME
      MEASURES: The reduction in activity over the grafts was measured for 2 hours.
      RESULTS: There was an immediate loss of activity to around 80% and thereafter a
      lower rate of cell loss to around 50%. No difference could be demonstrated in the
      loss from low flow compared to high flow grafts. All grafts were patent. There
      was no difference in thrombus weights. CONCLUSION: No difference could be
      demonstrated in seeded endothelial cell loss from a Dacron graft in vivo at low
      flow (50 ml/minute) compared with unrestricted flow (120-180 ml/minute).

PMID- 7828746
TI  - Arterial autografts and PTFE vascular microprostheses: similarities in the
      healing process.
AB  - A comparative study has been carried out dealing with the vascular healing
      process in two experimental vascular graft models to determine the differences or
      similarities between the two. One of the models consisted of the use of arterial
      autografts and the other of the implantation of vascular microprostheses of
      polytetrafluoroethylene (PTFE). The common iliac artery of female Sprague-Dawley
      rats was used. The length of the grafts in both models was 5 mm. A microsurgical
      technique was employed, and anticoagulant and antibiotic therapies were not used.
      The results were studied using light microscopy, transmission and scanning
      electron microscopies, autoradiography, and immunohistochemistry. A patency of
      100% was obtained in the arterial autografts, and 87.6% in the PTFE implants. The
      histopathological findings were as follows: a) the mechanisms of immediate
      postgrafting response were similar, with marked presence of fibrin and platelet
      deposition in the form of a nonthrombogenic monolayer; b) a "neoadventitia"
      formed over the implant in both models; c) the endothelialisation was complete in
      both types of grafts 2 to 3 weeks after implantation; d) an intimal hyperplastic
      response appeared in both, although at different times (in the first week in the
      autografts and at one month with the PTFE); e) white cell accumulation was
      significantly greater on the PTFE luminal surface than on the autograft. The
      intimal hyperplasia was formed mainly by secretory myocytes in the autografts,
      while in the PTFE implants, fibrosis predominated.

PMID- 7828747
TI  - The Asymptomatic Carotid Surgery Trial (ACST). Rationale and design. Steering
      Committee.

PMID- 7828748
TI  - Duplex scanning for grading aortoiliac obstructive disease and guiding treatment.
AB  - Standard assessment of aortoiliac obstructive disease (AIOD) includes
      arteriography preferably supplemented with femoral artery pressure (FAP)
      measurements. This study investigated the value of Duplex scanning in classifying
      AIOD and compared the outcome of Duplex scanning with clinical decision making.
      One-hundred-and-fifty-three aortoiliac segments of 87 patients were prospectively
      examined by Duplex scanning, arteriography, and FAP measurements to establish the
      presence or absence of significant AIOD. The results of these tests were compared
      to each other and to the subsequent vascular interventions and their success
      rates. Excellent agreement (kappa 0.82) was found between Duplex scanning and
      arteriography. The agreement between Duplex scanning and FAP measurements was
      much lower (kappa 0.52). The correlation between the performed treatment and the
      assessment of AIOD by Duplex scanning or arteriography was good, whereas the FAP
      results correlated only moderately with the performed treatment. Endovascular or
      operative treatment was actually performed in only 63% of the aortoiliac segments
      with an abnormal FAP test (success rate 80%). Aortoiliac segments with
      significant AIOD according to arteriography or Duplex scanning were treated
      invasively in 86% (success rate 81%) and 82% (success rate 80%), respectively. In
      conclusion, Duplex scanning can replace arteriography as a screening tool for the
      identification of treatable aortoiliac lesions whereas the value of FAP
      measurements in the decision making process is limited.

PMID- 7828749
TI  - Biochemical and molecular genetic studies of abdominal aortic aneurysm in an
      Irish population.
AB  - Abdominal aortic aneurysm (AAA) is a common disease of the elderly exhibiting a
      complex aetiology. In a survey of 82 Irish aneurysm patients, compared to 79 age-
      and sex-matched control subjects, we have investigated a number of potential
      biochemical and molecular genetic markers which are amenable to analysis from
      blood specimens and which might have predictive value for AAA. No significant
      differences were observed between patients and control subjects in relation to
      serum lipids, leucocyte elastase activity or serum alpha 1-antitrypsin
      concentration. We have used the polymerase chain reaction to screen the patient
      and control groups in search of disease-associated genetic variation on
      chromosome 16, particularly in the region of the Cholesteryl Ester Transfer
      Protein (CETP) gene. Although variation in allele frequencies was detected
      between patients and controls at the four marker loci studied, no significant
      gene-disease associations were detected. The absence of gene-disease associations
      in our study may indicate that the genetic component in the aetiology of AAA in
      Ireland differs from that in the UK. Alternatively, it may indicate that the high
      degree of polymorphism at microsatellite loci may make them unsuitable as markers
      for the study of gene-disease associations in moderately sized populations. We
      therefore conclude that the biochemical and molecular genetic markers which we
      have examined are of no predictive value, and that ultrasonography remains the
      screening modality of choice for abdominal aortic aneurysm.

PMID- 7828750
TI  - Percutaneous intentional extraluminal recanalisation of the femoropopliteal
      artery.
AB  - Percutaneous intentional extraluminal recanalisation (PIER) of the
      femoropopliteal artery is a new catheter technique to overcome long chronic
      occlusions. This technique was applied to 40 long chronic occlusions of the
      femoropopliteal segment. The mean length of the superficial femoral artery (SEA)
      occlusions was 16.9 cm, the mean length of the popliteal occlusions was 11.8 cm
      and the mean length of the femoropopliteal occlusions was 27.6 cm. Primary
      recanalisation success was 85%. Patency showed a significant correlation with
      poor initial angiographic result (p < 0.05). Life-time table analysis of the
      successful group demonstrated a primary clinical patency of 59% at 1 and 2 years
      and a secondary clinical patency of 71% at 1 year and 65% at 2 years. There were
      no serious complications related to this technique. PIER technique is simple and
      cost-effective, and shows a good initial success-rate with a promising 2 years
      clinical patency. This technique might be of importance for patients with a
      critical lower leg ischaemia, when there are contraindications for primary bypass
      surgery either from a technical or a general point of view.

PMID- 7828751
TI  - Endothelin-1 levels in ischaemia, reperfusion, and haemorrhagic shock in the
      canine infrarenal aortic revascularisation model.
AB  - Endothelin-1 (ET-1) is a potent vasoconstrictive polypeptide produced from
      vascular endothelial cells. The effects of ischaemia, reperfusion, and
      exsanguination on plasma ET-1 levels were studied and compared in the mongrel dog
      after infrarenal aortic cross clamping. Ischaemia produced a trend toward
      increased ET-1 serum levels (p < 0.07 with Bonferroni correction) that did not
      reach significance. Plasma ET-1 levels were significantly increased during
      reperfusion and even further elevations were found following exsanguination. We
      found a 2-3 fold increase in ET-1 levels following reperfusion (Initial 3.19 +/-
      0.27 pg/ml vs. Reperfusion maximum 6.32 +/- 0.72 pg/ml, Bonferroni p < 0.01).
      Haemorrhagic shock was associated with a 3-4 fold increase in ET-1 levels
      (Initial 3.19 +/- 0.27 pg/ml vs. Exsanguination maximum 8.37 +/- 0.97 pg/ml
      Bonferroni p < 0.001). These data reveal that ET-1 is released during reperfusion
      and exsanguination and may mediate remote vascular events associated with
      infrarenal aortic cross clamping and acute blood loss.

PMID- 7828752
TI  - Revision of the proximal aortic anastomosis after aortic bifurcation surgery.
AB  - The implantation of an aortic bifurcation graft (ABG) for treatment of occlusive
      (OD) and aneurysmal (AD) aortoiliac disease is a standard technique with good
      long-term results and a relatively low incidence of complications. In a
      retrospective review of our patients from 1964 to 1993 only 36/1520 patients were
      identified who required reoperation at the proximal aortic anastomosis after ABG.
      Indications were graft occlusion (15/36) and graft stenoses (2/36), refractory to
      graft thrombectomy, proximal aortic anastomotic aneurysms (11/36) or graft
      infection (8/36). Graft occlusion or stenosis most frequently led to aortic
      reoperation in the OD-group (53.5%), recurrent aneurysmal disease (37.5%) and
      graft infection (37.5%) were the dominant indications in the AD-group. Mean time
      interval to reoperation was shorter in cases of graft infection (35 +/- 33
      months) as compared with graft stenosis (66 +/- 58 months), graft occlusion (86
      +/- 49 months) or aortic anastomotic aneurysms (152 +/- 90 months). Of the
      reoperations, 92% were done electively, 8% as emergency procedures. The
      perioperative course was uneventful in 67% of patients. Overall mortality rate
      after elective revisional surgery was 3% but reached 66% in emergencies.
      Postoperative morbidity and mortality was related to preoperative morbidity and
      the urgency of surgery, not with the mode of aortic intervention nor indication.

PMID- 7828753
TI  - A statistical analysis of the growth of small abdominal aortic aneurysms.
AB  - Screening for abdominal aortic aneurysm has been offered to 13,000 patients. An
      overall compliance of 76% (range 51-99%) has been achieved. For those with an
      initial aortic diameter between 29 mm and 45 mm serial ultrasound scans are
      offered to monitor aortic change. Of the 302 cases followed up by repeated scans,
      93 have had more than 5 scans (mean of 7 scans) over a mean time period of 32.1
      months (range 15-63 months). The rate of change of all these aneurysms has been
      calculated using all data points and robust linear regression. It has been
      possible to postulate an algorithm for aortic growth. The influence of
      measurement precision and ultrasound quality assurance on the rescan interval is
      demonstrated and it is suggested that 2 years is a suitable rescan interval for
      aortas with diameter less than 40 mm.

PMID- 7828754
TI  - Common femoral vein compression by lymphocoele after femoropopliteal bypass
      surgery.

PMID- 7828755
TI  - Successful repair of a ruptured abdominal aortic aneurysm in a cardiac transplant
      patient.

PMID- 7828756
TI  - Calcaneal necrosis secondary to distal embolisation: a rare complication of
      peripheral intraarterial thrombolysis.

PMID- 7828757
TI  - An exceptional case of popliteal entrapment syndrome.

PMID- 7828758
TI  - Aberrant right subclavian artery.

PMID- 7828759
TI  - Thoracoscopic sympathectomy.

PMID- 7828760
TI  - Thoracoscopic sympathectomy.

PMID- 7828761
TI  - Thoracoscopic sympathectomy.

PMID- 7828762
TI  - Intermittent claudication.

PMID- 7828763
TI  - A theory of the value of children.
AB  - This paper uses a non-standard value assumption--uncertainty reduction--to
      explain parenthood. We begin by reviewing the inadequacies of normative and
      standard rational choice explanations of shifts in fertility behavior. Then we
      propose a theory of the value of children based on the uncertainty-reduction
      assumption. Next we generate a range of hypotheses that follow both from this
      assumption and from a subsidiary assumption of marital solidarity enhancement.
      Finally, we explore the extent to which implications based on these new ideas are
      supported by the relevant empirical literature.

PMID- 7828764
TI  - A multistate model of fecundability and sterility.
AB  - This paper develops a multistate hazards model for estimating fecundability and
      sterility from data on waiting times to conception. Important features of the
      model include separate sterile and nonsterile states, a distinction between
      preexisting sterility and sterility that begins after initiation of exposure, and
      log-normally distributed fecundability among nonsterile couples. Application of
      the model to data on first birth intervals from Taiwan, Sri Lanka, and the Amish
      shows that heterogeneity in fecundability is statistically significant at most
      ages, but that preexisting sterility and new sterility are unimportant before age
      40. These results suggest that sterility may not be an important determinant of
      natural fertility until later reproductive ages.

PMID- 7828765
TI  - Estimating African-American mortality from inaccurate data.
AB  - This paper evaluates the quality of vital statistics and census data for
      estimating African-American mortality over a period of six decades. The authors
      employ intercensal cohort comparisons and extinct generation estimates to
      demonstrate that conventionally constructed African-American death rates may be
      seriously flawed as early as age 50. Using the crude death rate at ages 50+ for
      1978-1982 in conjunction with estimated growth rates and two model life table
      systems, the authors estimate black age-specific death rates in 1978-1982. These
      results suggest that if a racial crossover in death rates occurs, the age pattern
      of mortality among African-Americans must be far outside the range observed in
      populations with more accurate data.

PMID- 7828766
TI  - Five decades of missing females in China.
AB  - This paper seeks to explain the dearth of females in the population of China in
      cohorts born from the late 1930s to the present. We demonstrate that in virtually
      all cohorts, the shortage of females in comparison with males is revealed when
      the cohort is first enumerated in a census. Subsequently it barely changes, an
      indication that female losses occur very early in life. Using the high-quality
      data from the censuses and fertility surveys in China, we show that many of the
      births of the girls missing in the censuses were not reported in the surveys
      because they died very young. The incidence of excess early female mortality
      (probably infanticide) declined precipitously in the Communist period, but not to
      zero. The recent escalation in the proportion of young females missing in China
      has been caused largely by rapidly escalating sex-selective abortion.

PMID- 7828767
TI  - Nonreporting of births or nonreporting of pregnancies? Some evidence from four
      rural counties in north China.
AB  - Coale and Banister argue that in China, elevated sex ratios in retrospective
      surveys are in part a function of collecting birth histories in a culture in
      which the definition of a birth may exclude mortality shortly after birth: an
      infant death in the West may be a stillbirth in east Asia. I present data from a
      recent sample survey featuring a retrospective pregnancy history. These data
      reveal that at least in the first pregnancy, from which the preponderance of
      sample births arise, there is no evidence of elevated female infant mortality or
      of high numbers of stillbirths, but that reported sex ratios are unusually high.
      The proportion of stillbirths grows for later pregnancies, but not enough to
      account for high sex ratios. Retrospective fertility data regarding recall over a
      recent interval are vexed less by a misunderstanding of what a live birth is than
      by a "misunderstanding" of what a (reportable) pregnancy is.

PMID- 7828768
TI  - Double jeopardy: interaction effects of marital and poverty status on the risk of
      mortality.
AB  - The purpose of this paper is to examine the hypothesis that marital and poverty
      status interact in their effects on mortality risks beyond their main effects.
      This study examines the epidemiological bases for applying an additive rather
      than a multiplicative specification when testing for interaction between two
      discrete risk factors. We specifically predict that risks associated with being
      nonmarried and with being poor interact to produce mortality risks that are
      greater than each risk acting independently. The analysis is based on men and
      women who were ages 25-74 during the 1971-1975 National Health and Nutrition
      Examination Survey I (NHANES I) and who were traced successfully in the NHANES I
      Epidemiologic Follow-Up Study in 1982-1984. Overall, being both poor and
      nonmarried places nonelderly (ages 25-64) men, but not women, at risk of
      mortality greater than that expected from the main effects. This study shows that
      for all-cause mortality, marital and poverty status interact for men but less so
      for women; these findings exist when interaction is assessed with either a
      multiplicative or an additive standard. This difference is most pronounced for
      poor, widowed men and (to a lesser degree) poor, divorced men. For
      violent/accidental deaths among men, the interaction effects are large on the
      basis of an additive model. Weak main and interaction effects were detected for
      the elderly (age 65+).

PMID- 7828769
TI  - Nativity concentration and internal migration among the foreign-born.
AB  - Are immigrants who live in states where large numbers of their compatriots reside
      more or less likely to migrate than those who live in other states? Using 1980
      U.S. Census data to address that question, the analysis shows that nativity
      concentration deters interstate migration but not migration within the same
      state. Residing in a state where fellow nationals live is a more important
      determinant of internal migration than human capital, immigration status, or a
      state's unemployment rate. New York State residence in 1975 also promotes
      interstate migration. This research suggests that social dimensions should be
      taken into account in modeling internal migration of the foreign-born.

PMID- 7828770
TI  - On the measurement of naturalization.
AB  - This paper proposes a new way of measuring naturalization, which takes into
      account both emigration and death. I argue that the new method corrects for
      underestimation and thus provides a more accurate measure of the concept. Using
      data from six groups of the 1973 immigrant cohort and multiple-decrement life
      table techniques, I estimated and compared naturalization measures derived from
      new and old methods. The results show that failure to control for emigration has
      a significant effect on the measurement of naturalization, particularly if an
      immigrant group has relatively high rate of emigration. Some further substantive
      implications of this new method are also explored.

PMID- 7828771
TI  - In search of Asian war brides.
AB  - Because of the long presence of U.S. soldiers in Asia, war-bride marriages
      involving servicemen and Asian women have been formed throughout the century. The
      literature, however, contains little empirically sound information on Asian war
      brides. This analysis develops a methodology to identify war brides and applies
      it to estimate the number of war brides from the six major Asian groups, using
      the national 1980 Public Use Microdata Sample. Further analysis comparing Asian
      war brides with other groups of Asian wives tends to support the traditional and
      lower socioeconomic images commonly associated with Asian war brides.

PMID- 7828772
TI  - [Type 2 (non-insulin-dependent) diabetes: a therapeutic problem not completely
      resolved].

PMID- 7828773
TI  - [Non Insulin Dependent Diabetes: metabolic and vascular disease. Conference
      proceedings. Paris, France, 26 March 1994].

PMID- 7828774
TI  - [Problems raised by the definition and epidemiology of type 2 (non-insulin
      dependent) diabetes throughout the world].
AB  - Many studies of Type 2 (non-insulin-dependent) diabetes mellitus assume that the
      condition is homogeneous and clearly defined. There are, however, several
      problems with these assumptions. Thus, definition of Type 2 diabetes is one of
      exclusion of other types (insulin-dependent, malnutrition-related, gestational
      and other rarer types) and inevitably contains a heterogeneous group of disorders
      the aetiology of which is largely unclear, and separation from the insulin
      dependent type can be problematic. Diagnosis is also imprecise in asymptomatic
      subjects due to the lack of accurate diagnostic tools and lack of clear
      distinction of impaired glucose tolerance. An alternative to the oral glucose
      tolerance test is urgently needed. Epidemiological studies of Type 2 diabetes and
      its complications are also fraught with difficulties due to variability of the
      oral glucose tolerance test, potential problems in glucose measurement,
      heterogeneity, population selection and problems in international comparisons due
      to differing age ranges and life expectancy. Great care is needed in all studies
      of Type 2 diabetes to ensure that the groups under study are properly selected,
      well-defined and fully described.

PMID- 7828775
TI  - [Anomalies of insulin secretion and type 2 diabetes: recent information].
AB  - Beta-cell dysfunction is prominent in Type 2 (non-insulin-dependent) diabetes
      mellitus. Four types of abnormalities have been described. Oscillatory pattern of
      insulin-secretion is impaired, with a loss of high frequency pulses and with a
      reduction in amplitude of slow oscillations. This impairment takes place early in
      the course of the disease, as does the loss of the first phase of insulin
      secretion after intravenous glucose. Quantitative (insulin deficiency in relative
      and absolute terms) and qualitative abnormalities (excess in proinsulin and in 32
      33 split proinsulin) have been also observed in Type 2 diabetes. One or several
      genetic defects seem to be responsible for the development of this beta-cell
      dysfunction and for Type 2 diabetes mellitus.

PMID- 7828776
TI  - [Insulin resistance: role in type 2 diabetes].
AB  - Type 2, non-insulin-dependent, diabetes is a disease of glucose homeostasis
      involving up to 5% of the adult population. The percentage of the population with
      glucose intolerance is even greater, 10%. These later patients are not diagnosed
      as "diabetics", but 50% of them have non-insulin-dependent diabetes. Globally,
      10% of the adult population has or will have Type 2 diabetes, a major health care
      problem. Characteristically, in patients with Type 2 diabetes, pancreatic insulin
      secretion is deficient, liver glucose production is increased during the post
      absorption period and peripheral glucose consumption, particularly in striated
      muscles, is decreased due to insulin resistance. There has been much progress in
      our understanding of the pathogenic mechanisms involved. When clinical
      manifestations have become apparent, the relative roles of defective insulin
      secretion and insulin resistance are difficult to distinguish. However, in
      persons with oral glucose intolerance or in persons with a high risk of
      developing Type 2 diabetes, these two mechanisms are more easily differentiated.
      High risk patients can be identified on the basis of our knowledge of genetic
      factors in Type 2 diabetes. The incidence of Type 2 diabetes is considerably
      increased in subjects with two diabetic parents. In addition to genetic factors,
      environmental factors also influence the development of non-insulin-dependent
      diabetes, contributing to the multifactorial nature of Type 2 diabetes. In order
      to establish the relative importance of these different factors, it is useful to
      define the different stages with characteristic degrees of metabolic disorder,
      insulin secretion abnormalities and insulin secretion.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7828777
TI  - [Implementation of the Declaration of St. Vincent].
AB  - The St Vincent Declaration, signed in 1989 by representatives of diabetes
      associations and experts in diabetology and public health, as well as
      representatives of European health ministers, is a programme designed to improve
      the quality of care provided to diabetics in Europe. In France, one of the tasks
      of the Conseil Superieur du Diabete (Diabetes Council) is to ensure that this
      programme is widely implemented. There are multiple facts to the implementation
      of this project: specific information for diabetics regarding their care,
      campaigns aimed at the public and health professionals, the setting up of
      epidemiological studies, and the organization of management strategies.
      Diabetologists are in the front line of professionals involved in the
      implementation of this programme, due to their involvement in diabetic education
      and in the treatment of diabetes and its complications. Even more than
      previously, the quality of life of the patients is a key objective.

PMID- 7828778
TI  - [Gliclazide: review of metabolic and vascular action].
AB  - Gliclazide is a second-generation sulfonylures that is widely used in the
      treatment of non-insulin-dependent diabetes mellitus (Type 2 diabetes). It has
      been recommended for use on the basis of both its metabolic and nonmetabolic
      effects. It has a clear beneficial effect on metabolic control in Type 2
      diabetes. Blood glucose and lipid levels are lowered. The glucose-lowering
      effects are secondary to both enhanced insulin secretion and a decrease in
      insulin resistance. The former is due to closure of a K+ adenosine triphosphate
      (ATP) channel in the beta cell. The mechanism whereby insulin action on the liver
      and muscle are potentiated remains unknown. It does not appear to involve the
      insulin receptor, and although glycogen synthase activation is enhanced, this is
      probably not specified. It has proven difficult to separate the metabolic effects
      of gliclazide form the effects of improved control. The metabolic actions are
      probably also shared with over sulfonylureas. Gliclazide also has beneficial
      effects on platelet behavior and function and on the endothelium, in addition to
      improving free radical status. These effects should be beneficial for the
      prevention of diabetic microangiopathy. Some evidence has appeared for the
      prevention of deterioration of diabetic retinopathy, but results are variable and
      more convincing studies are required. Many of the nonmetabolic effects of
      gliclazide appear to be unique to this agent. Gliclazide thus appears to be a
      reasonable choice in the treatment of Type 2 diabetes with diet failure, both
      from the metabolic and non-metabolic standpoint.

PMID- 7828779
TI  - [Cardiovascular risk factors in type 2 diabetes].
AB  - Morbidity and mortality through coronary atherosclerosis are higher in Type 2
      diabetic patients than in nondiabetic subjects, roughly by a factor of 2 in males
      and 3 in females. Methodological problems in attempting to weigh the relative
      effects of each factor make it difficult to accurately interpret the numerous
      epidemiological data already available. Three issues are discussed here:--Do
      diabetics have more "classic" risk factors than nondiabetics? The incidence of
      hypertension, lipid disorders, and even smoking is practically consistently
      higher in diabetics, with "diabetic" lipid disorders (decreased HDL cholesterol
      and hypertriglyceridemia) topping the list.--Do diabetics have specific risk
      factors which could explain the observed increase in coronary morbidity and
      mortality? The answer would appear to be yes, as patent microalbuminuria--between
      30 and 300 mg/24 hours--is found, as well as retinopathy and an increase in
      fibrinogen and PAI1 plasminogen activator inhibitor. Recent genetic studies have
      highlighted the role of Lp (a), and particularly that of angiotensin converting
      enzyme gene polymorphism (DD allele).--What are the respective roles of
      hyperglycalmia and elevated levels of circulating insulin? In contrast to the
      importance of insulin in nondiabetics as demonstrated in longitudinal studies,
      insulin appears to play a marginal or even nil role in diabetics once the disease
      is established. It is probably glycaemia itself which remains the fundamental
      factor, even though the mechanisms leading from hyperglycemia to macrovascular
      complications remain unknown.

PMID- 7828780
TI  - [Mechanisms of macrovascular involvement in diabetic subjects].
AB  - Diabetic macroangiopathy is often viewed as an accelerated and aggravated form of
      atherosclerosis. Several biological disturbances that are associated with
      diabetes partially account for a possible aggravation of atherosclerosis. Such
      are disorders of blood lipids (increased triglyceride concentration,
      modifications of low density lipoproteins) of haemostatis (increased platelet
      activity, decreased fibrinolytic activity) or of arterial vasomotility. Yet, many
      uncertainties and inconsistencies still obfuscate the links between diabetes and
      atherosclerosis, which remain hypothetical, and debatable. Clinical experience
      and all clinical epidemiological studies show that the incidence and severity of
      ischaemic arterial diseases (coronary heart disease, lower limb ischaemia,
      cerebral ischaemic events) are increased in diabetic individuals. However,
      intermediates other than worsened atherosclerosis may account for these
      associations. For instance, several anatomical epidemiological studies, based on
      routine autopsies, have note consistently found that atherosclerotic lesions
      (plaques) are larger and more extensive in diabetic than in non-diabetic
      individuals. The basic mechanisms of diabetic macroangiopathy could therefore be
      not as closely related to atherosclerosis as is usually thought. Among the non
      atherosclerotic lesions that could explain the increased arterial risk in
      diabetic patients, the best documented and most plausible is arteriosclerosis--a
      pure sclerosis of the arterial wall (without lipid deposition) which, in its
      advanced forms, can compromise tissue vascularization. Arteriosclerosis is
      considered as a normal consequence of arterial ageing which would be accelerated
      in diabetes. Chronic hyperglycaemia is and independent and influent marker of
      arterial risk in diabetic patients. It could stimulate arterial sclerosis by
      enhancing non-enzymatic glycation of various components of the arterial matrix,
      through formation of advanced glycation end-products (AGEs).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7828781
TI  - [Why is insulin tied to the prevalence of cardiovascular diseases without being a
      risk factor for their incidence?].
AB  - Insulin is frequently considered to be a risk factor for atherosclerosis (or for
      coronary and vascular disease). Furthermore, hyperinsulinaemia is claimed to be
      the primary cause underlying the other features which make up the insulin
      resistance syndrome. However, if proof of these assertions is based only on
      prospective studies, its value is limited. Only two studies, both carried out,
      surprisingly, in policemen, have shown convincingly that insulin was a coronary
      risk factor. In one of the studies, the Paris Prospective Study, the insulin
      coronary disease correlation was shown to subside with increasing duration of
      follow-up. The other prospective studies have failed to evidence a correlation
      between insulinaemia and cardiovascular events, even with univariate analysis.
      One study even showed a negative correlation between insulinaemia and coronary
      complications. In view of the fact that insulinaemia has been shown repeatedly to
      be associated with classic cardiovascular risk factors--systolic hypertension,
      decrease in HDL cholesterol, increase in triglycerides, and abdominal obesity--it
      is highly surprising that univariate analysis has not been able to show the same
      correlation between insulin and cardiovascular complications. In fact, the
      combination of elevated insulinaemia and classic risk factors may result in
      protection against the deleterious effects of these factors. Another possibility
      would be that insulinaemia is associated with unknown protective factors. Both
      hypotheses would account for the existence of a correlation between insulin and
      current cardiovascular disease, as well as the absence of correlation between
      insulin and later onset of cardiovascular disease.

PMID- 7828782
TI  - [Prevention of macroangiopathy of type 2 diabetes in clinical practice].
AB  - The increase in cardio-vascular morbidity of people with Type 2 diabetes is due
      to the frequent association of Type 2 diabetes with classical risk factors but
      also to diabetes per se, whatever the mechanisms involved. From a clinical point
      of view, it is important to stop smoking, with a great benefit, to treat
      hypertension with other drugs than diuretics or beta-blockers and to treat
      dyslipidaemia. The lipid abnormalities often improve with the only glycaemic
      control. In all cases, the normalisation of HbA1c is a very important therapeutic
      goal, by diet, exercise, oral hypoglycaemic drugs or insulin if necessary. The
      treatment will be especially useful in high risk patients, i.e. patients with
      coronary heart disease, patients with albuminuria, patients with more than 3 risk
      factors associated with diabetes and/or with high glycaemic levels.

PMID- 7828783
TI  - Bones and joints.

PMID- 7828784
TI  - Open spina bifida: a complete cohort reviewed 25 years after closure.
AB  - This study summarises the long-term results of non-selective treatment of open
      spina bifida. Every member of a consecutive series of 117 cases was ascertained
      22 to 28 years after closure of the back. 56 of the cohort had died. The
      condition of the 61 survivors ranged from normal to severe disability. Only 33 of
      the survivors were capable of living independently, 11 required supervision and
      some help, and 17 needed daily care which was generally provided by the parents.
      The two main determinants of disability and dependency were the extent of the
      neurological deficit and IQ. Improvements in the management of patients with open
      spina bifida have greatly reduced mortality, but they are less likely to
      influence long-term disability since that is dependent on the severity of the
      neurological deficit.

PMID- 7828785
TI  - The hip in cerebral palsy.

PMID- 7828786
TI  - Neurological dysfunction above cele level in children with spina bifida cystica:
      a prospective study to three years.
AB  - The aim of this study was to characterize the neurological dysfunction above the
      cele level in children with spina bifida cystica. 22 neonates were investigated
      prospectively to a median age of three years. Before primary closure of the
      spinal malformation and at three and 18 months of age, MRI and inspection of
      vocal cord function were performed. The children were also assessed by a physical
      therapist at 12 and 24 months, 19 children had a Chiari malformation, 18 children
      developed neurological dysfunction above the cele level. Children with signs of
      isolated motor impairment stabilized or improved during the second year. Six
      children developed severe functional impairment of respiration, feeding and motor
      performance within the first three months of life. Severe neurological
      signs/symptoms were associated with myeloschisis, clinical signs of a tethered
      cord and recurrent periods of shunt dysfunction.

PMID- 7828787
TI  - Genetic basis of specific language impairment: evidence from a twin study.
AB  - Concordance rates were compared for 63 monozygotic (MZ) and 27 dizygotic (DZ)
      same-sex twin pairs, aged seven years and over, selected because at least one
      twin met diagnostic criteria for specific speech or language impairment. There
      was significant heritability for developmental speech and language disorder,
      defined according to DSM-II-R criteria. When the definition of the phenotype was
      broadened to include those with a past history of disorder and those with a less
      pronounced discrepancy between verbal and non-verbal ability, concordance for MZ
      twins was close to 100 per cent, and that for DZ twins approximately 50 per cent.
      There was also close similarity between concordant twins for type of disorder.
      There is good evidence that genetic factors play a role in the aetiology of
      speech and language impairment; twin data may help us arrive at a clearer
      conception of the phenotype as well as quantifying the extent of the genetic
      contribution.

PMID- 7828788
TI  - Tactile control of isometric fingertip forces during grasping in children with
      cerebral palsy.
AB  - Sensory mechanisms and sensorimotor integration have often been thought to be
      disturbed in children with cerebral palsy (CP). The authors investigated the
      influence of tactile information from the fingertips on the isometric force
      regulation during the lift of a small object with the precision grip in children
      with CP and controls. Children with CP were able to modify their grip force
      according to friction between the fingertips and the object and could use tactile
      information for anticipatory control of the force-scaling of the precision grip,
      but they seemed to need predictable conditions and successive lifts to build up
      memory representation of an object's friction.

PMID- 7828789
TI  - [Late thrombolysis in acute myocardial infarct. Demonstration of myocardial
      tissue salvage by the assessment of pre- and post-thrombolytic perfusion and left
      ventricular function].
AB  - BACKGROUND: Pre and post treatment perfusion scintigraphy with Tc-99m-sestamibi
      is an accurate method to evaluate the effectiveness of thrombolytic therapy in
      patients with acute myocardial infarction. In the present study this method was
      used to verify whether thrombolytic therapy performed late (6 to 24 hours) after
      symptoms onset was still able to produce significant salvage of jeopardized
      myocardial tissue. METHODS: Fifteen patients (mean age 60.9 +/- 9 years) admitted
      to CCU 8-23 hours (mean 13.2 +/- 4 hours) after symptoms onset of their first
      acute myocardial infarction were studied. Both myocardial perfusion and left
      ventricular function were assessed before and after thrombolysis. Myocardial
      perfusion was studied using Tc-99m-sestamibi Single Photon Emission Tomography
      (SPET) before (pre-lysis SPET), 4.4 +/- 0.9 days (post-lysis SPET A) and 32 +/- 6
      days (post-lysis SPET B) after thrombolysis. Uptake defects were graded from 0 to
      4 using a 20-segment scheme. Regional ventricular function was evaluated using
      two-dimensional echocardiography before (pre-lysis ECHO), simultaneously with
      post-lysis SPET A (post-lysis ECHO A) and 32 +/- 4 days after treatment (post
      lysis ECHO B); asynergy was graded from 1 to 4. Global left ventricular function
      was estimated using gated blood pool imaging and measuring the ejection fraction
      (EF) 5.3 +/- 1 (GBP 1) and 32 +/- 4 days after treatment (GBP 2). Within 6-9 days
      of admission all patients underwent coronary angiography. RESULTS: In pre-lysis
      SPET all patients had uptaken defects (score range 17-52, mean 34.6 +/- 12).
      According to the comparison between pre-lysis SPET and post-lysis SPET A,
      patients were divided into two groups: 7 patients with perfusion recovery (Group
      I) and 8 patients with absent or minimal perfusion recovery (Group II). In Group
      I the mean uptaken score decreased significantly (from pre-lysis SPET 34.2 +/- 12
      to post-lysis SPET A 21.7 +/- 7, p < 0.05); in Group II the uptaken score
      remained unchanged (from pre-lysis SPET 34.8 +/- 12 to post-lysis SPET A 33.6 +/-
      12, ns). In post-lysis SPET B both groups showed a defect reduction compared to
      post-lysis SPET A; however, the defect score of SPET B in Group I was
      significantly lower than that in Group II (18.7 +/- 16 vs 30.1 +/- 10, p < 0.05).
      The asynergic score in pre-lysis ECHO was the same in the two groups (19.5 +/-
      4); in post-lysis ECHO A no significant decrease was observed in the two groups.
      In post-lysis ECHO B a significant decrease was seen in Group I (14.8 +/- 5, p <
      0.05 vs pre-lysis ECHO and vs post-lysis ECHO A), but not in Group II (19.8 +/-
      5, ns); the asynergic score in post-lysis ECHO B was significantly lower in Group
      I than in Group II (p < 0.05). In GBP 1 the EF was 38% +/- 6 in Group I and 40%
      +/- 6 in Group II (ns). In GBP 2 a significant increase was registered in Group I
      (47% +/- 10, p < 0.05), whereas in Group II the EF remained unchanged (40% +/- 6,
      ns). Coronary angiography showed a patent infarct related vessel in all Group I
      patients and in 2 Group II patients (p < 0.05). CONCLUSIONS: These results show
      that in patients with acute myocardial infarction treated with thrombolysis late
      after symptoms onset it is still possible to obtain an effective reperfusion and
      the consequent salvage of jeopardized tissue, as demonstrated by the recovery of
      both regional and global left ventricular function.

PMID- 7828790
TI  - [Does aortic insufficiency influence Doppler-derived calculation of the valvular
      area in patients with mitral stenosis?].
AB  - BACKGROUND: The evaluation of mitral valve area (MVA) in patients with mitral
      stenosis represents the main purpose of any diagnostic method, provided that MVA
      is a key parameter to indicate the need for valve surgery. The aim of this study
      was to assess whether the presence of aortic regurgitation associated with mitral
      stenosis affects the MVA measurement by left atrial pressure half time (PHT).
      METHODS: Eighty-nine patients with mitral valve stenosis (68 females and 21
      males, mean age 53.6 +/- 12.1 years), were studied. Fourty-eight patients (36
      females and 12 males) had a concomitant aortic regurgitation (AR group), whereas
      41 patients (32 females and 9 males) did not reflect any aortic valve involvement
      (no-AR group). Aortic regurgitation was graded on the basis of color flow
      analysis. The majority of patients had a slight to moderate regurgitation. MVA
      determination was carried out using both Hatle formula (220/PHT) and planimetric
      measurement in parasternal short axis view. RESULTS: Statistical analysis
      demonstrated a good correlation between the 2 MVA measurement in both groups (IA
      group: r = 0.9, p < 0.0001, SSE = 0.21 cm2, y = 0.91x + 0.05; no-IA group r =
      0.92, p < 0.0001, SSE = 0.22 cm2, y = 0.92x + 0.04). The concomitant aortic valve
      disease did not affect in any way the MVA measurement by means of the PHT method.
      CONCLUSIONS: The Doppler derived method appears to be reliable for estimating the
      mitral valve area in patients with mitral stenosis even in the presence of aortic
      regurgitation.

PMID- 7828791
TI  - [Combination of transesophageal atrial pacing and echo-dipyridamole test in the
      diagnosis of coronary disease in patients with suspected angina pectoris and
      negative exercise test].
AB  - BACKGROUND: Echo-dipyridamole test is an useful tool for non-invasive
      demonstration of inducible myocardial ischemia in patients with coronary artery
      disease, its sensitivity being consistently higher as compared with classic
      exercise stress testing. However, in patients with single vessel who often
      perform a normal or borderline stress test, even the sensibility of echo
      dipyridamole test is comparatively reduced. METHODS: In 19 patients with
      clinically suspected angina (effort-related in 4, at rest in 8, mixed in 7) and
      normal exercise stress test, standard echo-dipyridamole test was performed.
      Thereafter, rapid atrial pacing, a procedure associated with a sharp increase of
      myocardial oxygen consumption, was performed by means of a transoesophageal
      catheter during the proceeding 5 min and during 4 min of repeated dipyridamole
      0.56 mg/kg infusion. RESULTS: Standard echo-dipyridamole test induced ventricular
      wall motion abnormalities in 3 patients (one with borderline exercise stress
      test), whereas repeated pacing-sensitized procedure obtained wall motion
      abnormalities (apical, septal and lateral) in the same and in 4 additional
      patients. Coronary angiography demonstrated > 70% stenosis in 8/19 patients
      (single vessel disease in 5), 7 of whom had been correctly recognized by pacing
      dipyridamole test; therefore, sensitivity of the latter as compared with standard
      dipyridamole test was 87% and 37% respectively. The anatomic correlation of
      induced wall motion abnormalities with coronary arterial stenosis was
      demonstrated in all cases. Specificity was 100% with both methods. CONCLUSIONS:
      Although limited by its restricted patient population, this study suggests that
      atrial pacing, performed via transoesophageal catheter, can significantly improve
      the positive predictive value of echo-dipyridamole test in coronary artery
      disease. By means of this simple procedure, the possibility of non invasively
      diagnosing even single vessel stenosis in patients with inconclusive exercise
      stress testing can be significantly improved.

PMID- 7828792
TI  - [Prevalence and severity of mitral insufficiency and arrhythmia in mitral valve
      prolapse].
AB  - OBJECTIVES: The purpose of this study was to assess, using Doppler
      echocardiography and ambulatory electrocardiography in patients with mitral valve
      prolapse (MPV), the prevalence and severity of mitral regurgitation (MR) and
      arrhythmias. METHODS: Two groups of patients were compared: those with thickening
      and redundancy of the mitral valve leaflets, chordae lengthening and dilatation
      of the valvular ring (anatomic MVP; n = 40) and those with the only movement
      anomaly detected by 2D echocardiogram (functional MVP; n = 80). RESULTS:
      Significant (moderate or severe) MR was found in 4 (5%) of the 80 patients with
      functional MVP and in 20 (50%) of the 40 patients with anatomic MVP (p < 0.01).
      No significant difference in the prevalence of atrial and ventricular arrhythmias
      was found between patients with functional MPV without MR and 40 randomly chosen
      control subjects. Arrhythmias in patients with functional MVP complicated by MR
      were significantly more prevalent (p < 0.05) than in patients with functional MVP
      without MR. Patients with anatomic MVP had significantly more frequent and more
      complex arrhythmias than did patients with functional MVP complicated by MR (p <
      0.05). There was no significant difference in the prevalence of frequent and
      complex ventricular arrhythmias between patients with anatomic MVP and patients
      with functional MVP complicated by MR of comparable hemodynamic degree.
      CONCLUSIONS: These results indicate that prevalence of significant (moderate or
      severe) MR is higher and that frequent and complex arrhythmias are significantly
      more prevalent in patients with anatomic MVP. The prevalence of frequent and
      complex arrhythmias is similar in patients with comparable MR, whether the
      regurgitation is related to anatomic MVP or to functional MVP or not.

PMID- 7828793
TI  - [Isradipine versus diltiazem in the treatment of stable effort angina pectoris:
      ergometric evaluation in a crossover double-blind study].
AB  - OBJECTIVES: To evaluate the effects of isradipine (ISR) and diltiazem (DIL) on
      exercise tolerance and ischemic ST depression in patients with stable effort
      angina. METHODS: Fourteen out-patients, 9 males and 5 females, aged 46-65 years
      (mean +/- SD = 57 +/- 8), with ischemic heart disease and reproducible ST-segment
      depression on two consecutive exercise stress tests in baseline conditions,
      underwent a study consisting of 4 periods: 1 and 3 placebo, 2 and 4 at random ISR
      (5 mg b.i.d.) and DIL (120 mg b.i.d.). At the end of each period a multistage
      treadmill exercise stress test (Bruce protocol) was performed. RESULTS: Both
      drugs significantly (p < 0.001) increased ischemia time (IT) (0.1 mV ST
      depression) as compared to placebo, from 438 +/- 132 s. to 620 +/- 164 s. (ISR)
      and 583 +/- 147 s. (DIL) without statistical difference between two drugs (p =
      0.2), and significantly reduced (p < 0.002) the maximal ST depression, from -0.20
      +/- 0.11 mV to -0.07 +/- 0.07 mV (ISR) and -0.09 +/- 0.11 mV (DIL). At the IT,
      systolic blood pressure increased (p = 0.02), from 180 +/- 19 mm Hg to 187 +/- 15
      mm Hg (ISR) and 191 +/- 15 mm Hg (DIL); similarly, heart rate increased from 133
      +/- 24 bpm to 144 +/- 18 bpm (ISR: p = 0.002) and 140 +/- 17 bpm (DIL: p = NS).
      CONCLUSIONS: ISR and DIL, at the above dosage have showed an important and
      significant anti-ischemic effect (IT = +41.5% during ISR and +33.1% during DIL).

PMID- 7828794
TI  - [Percutaneous tricuspid valvuloplasty].
AB  - The authors herein describe the case of a 44 year old woman, who 14 years ago
      underwent surgical intervention after a rheumatic disease. A double mitral-aortic
      valvular implantation and a tricuspid commissurotomy was carried out. The patient
      come under our observation for severe congestive heart failure, while both
      mechanical prostheses were working well. Furthermore, the Doppler
      echocardiography showed a severe tricuspid stenosis (mean gradient = 8.6 mm Hg)
      and a concurrent mild to moderate valvular regurgitation. Because of her poor
      clinical condition and due to the high surgical risk it was decided to perform a
      balloon valvuloplasty of the tricuspid stenosis. The procedure, using the
      percutaneous femoral approach, was carried out with a TRIAD-TWIN AT (diameter =
      18 + 18 mm; length = 4 cm; Mansfield) catheter and an Amplatz guide wire was
      advanced up to the apex of the right ventricle. Both balloons were inflated
      simultaneously on three occasions to a maximum pressure of 3.5 atmospheres for
      60". At the end of the procedure there was the complete disappearance of
      telediastolic gradient, the valvular regurgitation remained unchanged (when
      compared to the pre-valvuloplasty control) and the mean trans-tricuspid gradient
      reduced to 4 mm Hg. Immediately following the procedure there was a remarkable,
      rapid hemodynamic improvement of the patient and at three months her condition is
      constant. In conclusion tricuspid valvuloplasty even using the percutaneous
      femoral approach can be performed and considered a simple and effective
      treatment.

PMID- 7828795
TI  - [Value of transesophageal echocardiography in the diagnosis of paravalvular
      aortic abscess].
AB  - Paravalvular abscesses are a serious complication of aortic endocarditis.
      Echocardiography is the method of choice for the visualization of the valve
      attached vegetations, however the detection of endocarditis-associated abscesses
      by transthoracic approach is extremely difficult. Recently transesophageal
      echocardiography has been proved as an excellent tool to correctly detect these
      lesions. We report on two patients with endocarditis-associated abscesses in whom
      transesophageal echocardiography allowed us to diagnose paravalvular abscesses
      not recognized by transthoracic echocardiography; furthermore in the first
      patient, performing two successive transesophageal examinations before and after
      antibiotic therapy, we could follow the evaluation of aortic abscess which became
      a fistula draining into the left ventricular outflow tract. In conclusion these
      two cases suggest that transesophageal echocardiography should be always
      performed in patients suspected or known to have endocarditis and that a
      following examination is indicated to assess any evolving echocardiographic
      finding.

PMID- 7828796
TI  - [Stratification of risk following discharge after acute myocardial infarct:
      prognostic significance of advanced age. Participants in the GISSI-2 study].

PMID- 7828797
TI  - [Heart failure in the aged].

PMID- 7828798
TI  - [Re: syndrome X].

PMID- 7828799
TI  - [Stress echocardiography in the diagnosis of ischemic heart disease].

PMID- 7828800
TI  - [The resources diminish, health systems change: 2 examples, the English health
      system and the American health system].

PMID- 7828801
TI  - [Comparison of old and new health care reform].

PMID- 7828802
TI  - [National cardiologic structures and procedures: considerations on the current
      situation].

PMID- 7828803
TI  - [Areas of economic responsibility of the cardiologist: criteria of the evaluation
      of costs].

PMID- 7828804
TI  - [Health means. Rationale and implications of the choice. The case of angina
      pectoris].

PMID- 7828805
TI  - [Appropriateness and control of the quality of health services].

PMID- 7828806
TI  - [Guidelines as a tool in appropriate medical decisions and rationalization of
      costs].

PMID- 7828807
TI  - The Holliday junction on its thirtieth anniversary.

PMID- 7828808
TI  - Involvement of a replicative DNA helicase of bacteriophage T4 in DNA
      recombination.
AB  - Bacteriophage T4 gene 41 encodes a replicative DNA helicase that is a subunit of
      the primosome which is essential for lagging-strand DNA synthesis. A mutation,
      rrh, was generated and selected in the helicase gene on the basis of limited DNA
      replication that ceases early. The survival of ultraviolet-irradiated phage and
      the frequency of genetic recombination are reduced by rrh. In addition, rrh
      diminishes the production of concatemeric DNA. These results strongly suggest
      that the gene 41 replicative helicase participates in DNA recombination.

PMID- 7828809
TI  - Population dynamics of a Lac- strain of Escherichia coli during selection for
      lactose utilization.
AB  - During selection for lactose utilization, Lac+ revertants of FC40, a Lac- strain
      of Escherichia coli, appear at a high rate. Yet, no Lac+ revertants appear in the
      absence of lactose, or in its presence if the cells have another, unfulfilled
      requirement for growth. This study investigates more fully the population
      dynamics of FC40 when incubated in the absence of a carbon source or when
      undergoing selection for lactose utilization. In the absence of a carbon source,
      the viable cell numbers do not change over 6 days. When incubated in liquid
      lactose medium, Lac- cells do not undergo any measurable increase in numbers or
      in turbidity for at least 2 days. When FC40 is plated on lactose minimum medium
      in the presence of scavenger cells, the upper limit to the amount of growth of
      Lac- cells during 5 days is one doubling, and there is no evidence for turnover
      (i.e., a balance between growth and death). The presence of a minority population
      that could form microcolonies was not detected. The implications of these
      results, plus the fact that the appearance of Lac+ revertants during lactose
      selection is nearly constant with time, are discussed in reference to several
      models that have been postulated to account for adaptive mutations.

PMID- 7828810
TI  - Spontaneous mutation in Escherichia coli containing the dnaE911 DNA polymerase
      antimutator allele.
AB  - We have previously isolated mutants of Escherichia coli that replicate their DNA
      with increased fidelity. These mutants have a mutation in the dnaE gene, encoding
      the alpha subunit of DNA polymerase III. They were isolated in a mismatch-repair
      defective mutL background, in which mutations can be considered to represent
      uncorrected DNA replication errors. In the present study we analyze the effect of
      one of these alleles, dnaE911, on spontaneous mutagenesis in a mismatch-repair
      proficient background. In this background, spontaneous mutations may be the sum
      of uncorrected replication errors and mutations resulting from other pathways.
      Hence, the effect of the dnaE allele may provide insights into the contribution
      of uncorrected DNA replication errors to spontaneous mutation. The data show that
      dnaE911 decreases the level of Rifr, lacI and galK mutations in this background
      by 1.5-2-fold. DNA sequencing of 748 forward mutants in the lacI gene reveals
      that this effect has a clear specificity. Transversions are decreased by
      approximately 3-fold, whereas transitions, frameshifts, deletions and
      duplications remain essentially unchanged. Among the transversions, A.T-->T.A are
      affected most strongly (approximately 6-fold). In addition to this effect on
      transversions within the lacI gene, one previously recognized A.T-->G.C base-pair
      substitution hotspot in the lac operator is also reduced (approximately 5-fold).
      The data are discussed in the light of the role of DNA replication errors in
      spontaneous mutation, as well as other possible explanations for the observed
      antimutator effects.

PMID- 7828811
TI  - Characterization of G1 checkpoint control in the yeast Saccharomyces cerevisiae
      following exposure to DNA-damaging agents.
AB  - The delay of S-phase following treatment of yeast cells with DNA-damaging agents
      is an actively regulated response that requires functional RAD9 and RAD24 genes.
      An analysis of cell cycle arrest indicates the existence of (at least) two
      checkpoints for damaged DNA prior to S-phase; one at START (a G1 checkpoint
      characterized by pheromone sensitivity of arrested cells) and one between the
      CDC4- and CDC7-mediated steps (termed the G1/S checkpoint). When a dna1-1 mutant
      (that affects early events of replicon initiation) also carries a rad9 deletion
      mutation, it manifests a failure to arrest in G1/S following incubation at the
      restrictive temperature. This failure to execute regulated G1/S arrest is
      correlated with enhanced thermosensitivity of colony-forming ability. In an
      attempt to characterize the signal for RAD9 gene-dependent G1 and G1/S cell cycle
      arrest, we examined the influence of the continued presence of unexcised
      photoproducts. In mutants defective in nucleotide excision repair, cessation of S
      phase was observed at much lower doses of UV radiation compared to excision
      proficient cells. However, this response was not RAD9-dependent. We suggest that
      an intermediate of nucleotide excision repair, such as DNA strand breaks or
      single-stranded DNA tracts, is required to activate RAD9-dependent G1 and G1/S
      checkpoint controls.

PMID- 7828812
TI  - Mapping of DBR1 and YPK1 suggests a major revision of the genetic map of the left
      arm of Saccharomyces cerevisiae Chromosome XI.
AB  - The Saccharomyces cerevisiae dbr1 mutation has been mapped on the left arm of
      chromosome XI. XIL is a chromosome arm that was until now rather sparsely
      populated with accurately mapped markers. On the basis of physical data, the
      overall order of markers is inverted relative to the existing genetic map of XI.
      We present tetrad analyses using a variety of markers on XI that indicate that
      the existing genetic map of XIL should be inverted, at least for the strains in
      which our mapping was carried out, and probably for other S. cerevisiae strains.

PMID- 7828813
TI  - Isolation of the mating-type genes of the phytopathogenic fungus Magnaporthe
      grisea using genomic subtraction.
AB  - Using genomic subtraction, we isolated the mating-type genes (Mat1-1 and Mat1-2)
      of the rice blast fungus, Magnaporthe grisea. Transformation of M. grisea strains
      of one mating type with a linearized cosmid clone carrying the opposite mating
      type gene resulted in many "dual maters," strains that contain both mating-type
      genes and successfully mate with Mat1-1 and Mat1-2 testers. Dual maters differed
      in the frequency of production of perithecia in pure culture. Ascospores isolated
      from these homothallic crosses were either Mat1-1 or Mat1-2, but there were no
      dual maters. Most conidia from dual maters also had one or the other of the
      mating-type genes, but not both. Thus, dual maters appear to lose one of the
      mating-type genes during vegetative growth. The incidence of self-mating in dual
      maters appears to depend on the co-occurrence of strains with each mating type in
      vegetative cultures. In rare transformants, the incoming sequences had replaced
      the resident mating-type gene. Nearly isogenic pairs produced from three M.
      grisea laboratory strains were mated to investigate their fertility. One
      transformant with switched mating type appears to have a mutation that impairs
      the development of asci when its mating partner has a similar genetic background.
      The M. grisea Mat1-1 and Mat1-2 genes are idiomorphs approximately 2.5 and 3.5 kb
      in length, respectively.

PMID- 7828814
TI  - A temperature-sensitive mutation of the temperature-regulated SerH3 i-antigen
      gene of Tetrahymena thermophila: implications for regulation of mutual exclusion.
AB  - The Ser genes of Tetrahymena thermophila specify alternative forms of a major
      cell surface glycoprotein, the immobilization or i-antigen (i-ag). Regulation of
      i-ag expression assures that at least one i-ag gene is expressed at all times. To
      learn more about the regulatory system and the possible role of i-ag itself, we
      studied SerH3-ts1, a temperature-sensitive allele of the temperature-regulated
      SerH3 gene normally expressed from 20-36 degrees. In homozygotes grown at the
      nonpermissive temperature (> 32 degrees), H3 is not present on the cell surface,
      but the gene continues to be transcribed until its 36 degrees cutoff. H3 formed
      at the permissive temperature is stable at nonpermissive temperatures, indicating
      that SerH3-ts1 is temperature-sensitive for synthesis rather than function. At
      nonpermissive temperatures, the S i-ag is expressed in place of H3. This result
      suggests that normal H protein may play a role in regulating S expression. SerH3
      ts1 was isolated following mutagenesis with N-methyl-N'-nitro-N-nitrosoguanidine
      (MNNG). Sequencing of SerH3-ts1 revealed a single A --> G transition at
      nucleotide 473, resulting in the substitution of glycine for aspartate. The
      affected residue is conserved in the internal repeats comprising the H protein,
      and the charge difference correlates with changes in electrophoretic mobility of
      the H3 protein.

PMID- 7828815
TI  - Multiple chemosensory defects in daf-11 and daf-21 mutants of Caenorhabditis
      elegans.
AB  - Phenotypic analysis of the daf-11 and daf-21 mutants of Caenorhabditis elegans
      suggests that they have defects in components shared by processes analogous to
      vertebrate taste and olfaction. daf-11 and daf-21 mutations were previously shown
      to cause inappropriate response to the dauer-inducing pheromone. By mutational
      analysis and by disabling specific chemosensory sensilla with a laser, we show
      that neurons in the amphid sensilla are required for this pheromone response.
      Using behavioral assays, we find that daf-11 and daf-21 mutants are not defective
      in avoidance of certain non-volatile repellents, but are defective in taxis to
      non-volatile attractants. In addition, both mutants are defective in taxis to
      volatile attractants detected primarily by the amphid neuron AWC, but respond
      normally to volatile attractants detected primarily by AWA. We propose that daf
      11 and daf-21 mediate sensory transduction for both volatile and non-volatile
      compounds in specific amphid neurons.

PMID- 7828816
TI  - Sequenced alleles of the Caenorhabditis elegans sex-determining gene her-1
      include a novel class of conditional promoter mutations.
AB  - In the control of Caenorhabditis elegans sex determination, the her-1 gene must
      normally be activated to allow male development of XO animals and deactivated to
      allow hermaphrodite development of XX animals. The gene is regulated at the
      transcriptional level and has two nested male-specific transcripts. The larger of
      these encodes a small, novel, cysteine-rich protein responsible for masculinizing
      activity. Of the 32 extant mutant alleles, 30 cause partial or complete loss of
      masculinizing function (lf), while 2 are gain-of-function (gf) alleles resulting
      in abnormal masculinization of XX animals. We have identified the DNA sequence
      changes in each of these 32 alleles. Most affect the protein coding functions of
      the gene, but six are in the promoter region, including the two gf mutations.
      These two mutations may define a binding site for negative regulators of her-1.
      Three of the four remaining promoter mutations are single base changes that
      cause, surprisingly, temperature-sensitive loss of her-1 function. Such
      conditional promoter mutations have previously not been found among either
      prokaryotic or eukaryotic mutants analyzed at the molecular level.

PMID- 7828817
TI  - Genetics of hybrid male sterility between drosophila sibling species: a complex
      web of epistasis is revealed in interspecific studies.
AB  - To study the genetic differences responsible for the sterility of their male
      hybrids, we introgressed small segments of an X chromosome from Drosophila
      simulans into a pure Drosophila mauritiana genetic background, then assessed the
      fertility of males carrying heterospecific introgressions of varying size.
      Although this analysis examined less than 20% of the X chromosome (roughly 5% of
      the euchromatic portion of the D. simulans genome), and the segments were
      introgressed in only one direction, a minimum of four factors that contribute to
      hybrid male sterility were revealed. At least two of the factors exhibited strong
      epistasis: males carrying either factor alone were consistently fertile, whereas
      males carrying both factors together were always sterile. Distinct spermatogenic
      phenotypes were observed for sterile introgressions of different lengths, and it
      appeared that an interaction between introgressed segments also influenced the
      stage of spermatogenic defect. Males with one category of introgression often
      produced large quantities of motile sperm and were observed copulating, but never
      inseminated females. Evidently these two species have diverged at a large number
      of loci which have varied effects on hybrid male fertility. By extrapolation, we
      estimate that there are at least 40 such loci on the X chromosome alone. Because
      these species exhibit little DNA-sequence divergence at arbitrarily chosen loci,
      it seems unlikely that the extensive functional divergence observed could be due
      mainly to random genetic drift. Significant epistasis between conspecific genes
      appears to be a common component of hybrid sterility between recently diverged
      species of Drosophila. The linkage relationships of interacting factors could
      shed light on the role played by epistatic selection in the dynamics of the
      allele substitutions responsible for reproductive barriers between species.

PMID- 7828818
TI  - Linearity Versus nonlinearity of offspring-parent regression: an experimental
      study of Drosophila melanogaster.
AB  - An experiment was conducted to investigate the offspring-parent regression for
      three quantitative traits (weight, abdominal bristles and wing length) in
      Drosophila melanogaster. Linear and polynomial models were fitted for the
      regressions of a character in offspring on both parents. It is demonstrated that
      responses by the characters to selection predicted by the nonlinear regressions
      may differ substantially from those predicted by the linear regressions. This is
      true even, and especially, if selection is weak. The realized heritability for a
      character under selection is shown to be determined not only by the offspring
      parent regression but also by the distribution of the character and by the form
      and strength of selection.

PMID- 7828819
TI  - Structure, expression and duplication of genes which encode phosphoglyceromutase
      of Drosophila melanogaster.
AB  - We report here the isolation and characterization of genes from Drosophila that
      encode the glycolytic enzyme phosphoglyceromutase (PGLYM). Two genomic regions
      have been isolated that have potential to encode PGLYM. Their cytogenetic
      localizations have been determined by in situ hybridization to salivary gland
      chromosomes. One gene, Pglym78, is found at 78A/B and the other, Pglym87, at
      87B4,5 of the Drosophila polytene map. Pglym78 transcription follows a
      developmental pattern similar to other glycolytic genes in Drosophila, i.e.,
      substantial maternal transcript deposited during oogenesis; a decline in
      abundance in the first half of embryogenesis; a subsequent increase in the second
      half of embryogenesis which continues throughout larval life; a decline in pupae
      and a second increase to a plateau in adults. This transcript has been mapped by
      cDNA and genomic sequence comparison, RNase protection, and primer extension.
      Using similar analyses transcripts of Pglym87 could not be detected. Pglym78 has
      two introns which interrupt the coding region, while the Pglym87 gene lacks
      introns. This and other features support a model of retrotransposition mediated
      gene duplication for the origin of Pglym87. The apparent absence of a complete,
      intact coding frame and transcript suggest that Pglym87 is a pseudogene. However,
      retention of reading frame and codon bias suggests that Pglym87 may retain coding
      function, or may have been inactivated recently, substantially after the time of
      duplication, or that the molecular evolution of Pglym87 is unusual. Similarities
      of the unusual molecular evolution of Pglym87 and other proposed pseudogenes are
      discussed.

PMID- 7828820
TI  - Suppressor U1 snRNAs in Drosophila.
AB  - Although the role of U1 small nuclear RNAs (snRNAs) in 5' splice site recognition
      is well established, suppressor U1 snRNAs active in intact multicellular animals
      have been lacking. Here we describe suppression of a 5' splice site mutation in
      the Drosophila melanogaster white gene (wDR18) by compensatory changes in U1
      snRNA. Mutation of positions -1 and +6 of the 5' splice site of the second intron
      (ACG[GTGAGT to ACC]GTGAGC) results in the accumulation of RNA retaining this 74
      nucleotide intron in both transfected cells and transgenic flies. U1-3G, a
      suppressor U1 snRNA which restores base-pairing at position +6 of the mutant
      intron, increases the ratio of spliced to unspliced wDR18 RNA up to fivefold in
      transfected Schneider cells and increases eye pigmentation in wDR18 flies. U1-9G,
      which targets position -1, suppresses wDR18 in transfected cells less well. U1
      3G,9G has the same effect as U1-3G although it accumulates to lower levels.
      Suppression of wDR18 has revealed that the U1b embryonic variant (G134 to U) is
      active in Schneider cells and pupal eye discs. However, the combination of 9G
      with 134U leads to reduced accumulation of both U1b-9G and U1b-3G,9G, possibly
      because nucleotides 9 and 134 both participate in a potential long-range
      intramolecular base-pairing interaction. High levels of functional U1-3G
      suppressor reduce both viability and fertility in transformed flies. These
      results show that, despite the difficulties inherent in stably altering splice
      site selection in multicellular organisms, it is possible to obtain suppressor U1
      snRNAs in flies.

PMID- 7828821
TI  - The effect of an intronic polymorphism on alcohol dehydrogenase expression in
      Drosophila melanogaster.
AB  - Several lines of evidence indicate that natural selection controls the
      frequencies of an allozyme polymorphism at the alcohol dehydrogenase (Adh) locus
      in Drosophila melanogaster. However, because of associations among sequence
      polymorphisms in the Adh region, it is not clear whether selection acts directly
      (or solely) on the allozymic site. This problem has been approached by using in
      vitro mutagenesis to distinguish among the effects on Adh expression of
      individual polymorphisms. This study shows that a polymorphism within the first
      Adh intron (delta 1) has a significant effect on the level of ADH protein. Like
      the allozyme, delta 1 shows a geographic cline in frequency, indicating that it
      may also be a target of natural selection. These results suggest that multisite
      selection models may be required to understand the evolutionary dynamics of
      individual loci.

PMID- 7828822
TI  - Enhancer traps in the Drosophila bithorax complex mark parasegmental domains.
AB  - Eight P elements carrying a beta-galactosidase (lacZ) reporter have been mapped
      to sites within the Drosophila bithorax complex. The bithorax complex contains
      three homeotic genes, and at least nine regulatory regions which control their
      expression in successive parasegments of the fly. The enhancer traps inserted at
      the promoter of one of the genes, Ultrabithorax, express lacZ in patterns which
      mimic the Ultrabithorax protein pattern. Enhancer traps in the regulatory regions
      do not mimic the endogenous genes, but express lacZ globally in the relevant
      parasegments. Some P elements carry large DNA fragments upstream of the lacZ
      promoter but internal to the P element. In cases where these internal sequences
      specify a lacZ pattern, that pattern is generally suppressed when the element is
      inserted in the bithorax complex. In embryos mutant for genes of the Polycomb
      group, the lacZ expression from the enhancer traps spreads to all segments. Thus,
      the enhancer traps reveal parasegmental domains that are maintained by Polycomb
      mediated repression. Such domains may be realized by parasegmental differences in
      chromatin structure.

PMID- 7828823
TI  - Chromosome damage and early developmental arrest caused by the Rex element of
      Drosophila melanogaster.
AB  - Rex (Ribosomal exchange) is a genetically identified repeated element within the
      ribosomal DNA (rDNA) of Drosophila melanogaster. Rex has a semidominant maternal
      effect that promotes exchange between and within rDNA arrays in the first few
      embryonic mitoses. Several of Rex's genetic properties suggest that its primary
      effect is rDNA-specific chromosome breakage that is resolved by recombination. We
      report here that rDNA crossovers are only a small, surviving minority of Rex
      induced events. Cytology of embryos produced by Rex-homozygous females reveals
      obvious chromosome damage in at least a quarter of the embryos within the first
      three mitotic divisions. More than half of the embryos produced by Rex females
      die, and the developmental arrest is among the earliest reported for any maternal
      effect lethal. The striking lethal phenotype suggests that embryos with early
      chromosome damage could be particularly fruitful subjects for analysis of the
      cell biology of early embryos.

PMID- 7828824
TI  - Mutations in calphotin, the gene encoding a Drosophila photoreceptor cell
      specific calcium-binding protein, reveal roles in cellular morphogenesis and
      survival.
AB  - Calphotin is a Drosophila photoreceptor cell-specific protein expressed very
      early in eye development, at the time when cell-type decisions are being made.
      Calphotin is a very hydrophobic and proline-rich protein which lacks obvious
      transmembrane domains. The cDNA encoding Calphotin was mapped to a region removed
      by a set of existing chromosomal deletions. Mutations that alter photoreceptor
      cell structure and development were isolated that fail to complement these
      deletions. These mutations fall into two classes. Class I mutations alter the
      structure of the rhabdomere, a photoreceptor cell organelle specialized for
      phototransduction. Class II mutations have rough eyes, due to misorientation of
      the rhabdomeres and photoreceptor cell death. Transformation rescue of these
      phenotypes in transgenic flies bearing calphotin genomic DNA indicates that both
      classes of mutations are in the calphotin gene. Analysis of these mutations
      suggest that Calphotin plays important roles in both rhabdomere development and
      in photoreceptor cell survival.

PMID- 7828825
TI  - Complete DNA sequence of the mitochondrial genome of the black chiton, Katharina
      tunicata.
AB  - The DNA sequence of the 15,532-base pair (bp) mitochondrial DNA (mtDNA) of the
      chiton Katharina tunicata has been determined. The 37 genes typical of metazoan
      mtDNA are present: 13 for protein subunits involved in oxidative phosphorylation,
      2 for rRNAs and 22 for tRNAs. The gene arrangement resembles those of arthropods
      much more than that of another mollusc, the bivalve Mytilus edulis. Most genes
      abut directly or overlap, and abbreviated stop codons are inferred for four
      genes. Four junctions between adjacent pairs of protein genes lack intervening
      tRNA genes; however, at each of these junctions there is a sequence immediately
      adjacent to the start codon of the downstream gene that is capable of forming a
      stem-and-loop structure. Analysis of the tRNA gene sequences suggests that the D
      arm is unpaired in tRNA(ser)(AGN), which is typical of metazoan mtDNAs, and also
      in tRNA(ser)(UCN), a condition found previously only in nematode mtDNAs. There
      are two additional sequences in Katharina mtDNA that can be folded into
      structures resembling tRNAs; whether these are functional genes is unknown. All
      possible codons except the stop codons TAA and TAG are used in the protein
      encoding genes, and Katharina mtDNA appears to use the same variation of the
      mitochondrial genetic code that is used in Drosophila and Mytilus. Translation
      initiates at the codons ATG, ATA and GTG. A + T richness appears to have affected
      codon usage patterns and, perhaps, the amino acid composition of the encoded
      proteins. A 142-bp non-coding region between tRNA(glu) and CO3 contains a 72-bp
      tract of alternating A and T.

PMID- 7828826
TI  - Distribution of exchanges upon homologous recombination of exogenous DNA in
      Xenopus laevis oocytes.
AB  - Homologous recombination between DNA molecules injected into Xenopus oocyte
      nuclei was investigated by examining the recovery of information from
      differentially marked parental sequences. The injected recombination substrate
      was a linear DNA with terminal direct repeats of 1246 bp; one repeat differed
      from the other by eight single base-pair substitutions, distributed throughout
      the region of homology, each of which created or destroyed a restriction enzyme
      site. Recombination products were recovered and analyzed for their content of the
      diagnostic sites, either directly by Southern blot-hybridization or after cloning
      in bacteria. The majority (76%) of the cloned products appeared to be the result
      of simple exchanges-i.e., there was one sharp transition from sequences derived
      from one parent to sequences derived from the other. These simple exchanges were
      concentrated near the ends of the homologous interval and, thus, near the sites
      of the original molecular ends. Placing marked sites on only one side of the
      homologous overlap showed that marker recovery was governed largely by the
      positions of the molecular ends and not by the markers themselves. When a
      terminal nonhomology was present at one end of the substrate, the yield of
      recombinants was sharply decreased, but the pattern of exchanges was not
      affected, suggesting that products from end-blocked substrates arise by the same
      recombination pathway. Because of considerable evidence supporting a
      nonconservative, resection-annealing mechanism for recombination in oocytes, we
      interpret the distribution of exchanges as resulting from long-patch repair of
      extensive heteroduplex intermediates.

PMID- 7828827
TI  - Repair of heteroduplex DNA in Xenopus laevis oocytes.
AB  - We have hypothesized that the inheritance of heteroallelic markers during
      recombination of homologous DNAs in Xenopus oocytes is determined by resolution
      of a heteroduplex intermediate containing multiple single-base mismatches. To
      test this idea, we prepared synthetic heteroduplexes carrying 8 separate mispairs
      in vitro and injected them into oocyte nuclei. DNA was recovered and analyzed
      directly, by Southern blot-hybridization, and indirectly, by cloning individual
      repair products in bacteria. Mismatch correction was quite efficient in the
      oocytes; markers on the same strand were commonly co-corrected, indicating a long
      patch mechanism; and the distribution of markers was very similar to that
      obtained by recombination. This supports our interpretation of the recombination
      outcome in terms of a resection-annealing mechanism. The injected heteroduplexes
      carried strand breaks (nicks) as a result of their method of preparation. We
      tested the idea that mismatch correction might be nick-directed by ligating the
      strands of the heteroduplex substrate to form covalently closed circles. Repair
      in oocytes was still efficient, and long patches predominated; but the pattern of
      recovered markers was quite different than with the nicked substrate. This
      suggests that nicks, when present, do indeed direct repair, but that, in their
      absence, recognition of specific mismatches governs repair of the ligated
      heteroduplexes.

PMID- 7828828
TI  - Genetic analysis of systematic mitochondrial heteroplasmy in rabbits.
AB  - One unusual property of rabbit mitochondrial DNA (mtDNA) is the existence of
      repeated 153-bp motifs in the vicinity of the replication origin of its H strand.
      Furthermore, every individual is heteroplasmic: it carries mtDNA molecules with a
      variable number of repeats. A systematic study of 8 females and their progeny has
      been devised to analyze mtDNA transmission through generations. The results
      suggest that three mechanisms are acting simultaneously. (1) Genetic drift in the
      germ line is revealed by the evolution of heteroplasmy when two major molecular
      forms are present in a female. (2) A high mutation rate (around 10(-2) per animal
      generation) generating molecular diversity, by deletion and addition of repeated
      units, is required to explain the observation of heteroplasmy in every
      individual. Moreover, the rates of mutation from the most frequent type to the
      other types are unequal. The deletion of one unit is more frequent than a
      deletion of two units, which is in turn more frequent than a deletion of three.
      (3) Selection for shorter molecules in somatic cells is probable. The frequency
      distribution of mtDNA types depends on the organ analyzed (kidney-spleen and
      liver vs. gonads).

PMID- 7828829
TI  - Genetic epilepsy model derived from common inbred mouse strains.
AB  - The recombinant inbred mouse strain, SWXL-4, exhibits tonic-clonic and
      generalized seizures similar to the commonest epilepsies in humans. In SWXL-4
      animals, seizures are observed following routine handling at about 80 days of age
      and may be induced as early as 55 days by rhythmic gentle tossing. Seizures are
      accompanied by rapid, bilateral high frequency spike cortical discharges and
      followed by a quiescent post-ictal phase. Immunohistochemistry of the immediate
      early gene products c-Fos and c-Jun revealed abnormal activation within cortical
      and limbic structures. The seizure phenotype of SWXL-4 can be explained and
      replicated fully by the inheritance of susceptibility alleles from its progenitor
      strains, SWR/J and C57L/J. Outcrosses of SWXL-4 with most other common inbred
      strains result in F1 hybrids that have seizure at least as frequently as SWXL-4
      itself. Quantitative trait locus mapping reveals a seizure frequency determinant,
      Szf1, near the pink-eyed dilution locus on chromosome 7, accounting for up to 32%
      of the genetic variance in an F2 intercross between SWXL-4 and the linkage
      testing strain ABP/Le. These studies demonstrate that common strains of mice such
      as SWR and C57L contain latent epilepsy susceptibility alleles. Although the
      inheritance of susceptibility may be complex, these results imply that a number
      of potentially important and practical, noninvasive models for this disorder can
      be constructed and studied in crosses between common mouse strains.

PMID- 7828830
TI  - The murine dilute suppressor gene encodes a cell autonomous suppressor.
AB  - The murine dilute suppressor gene (dsu) suppresses the coat-color phenotype of
      three pigment mutations, dilute (d), ashen (ash) and leaden (ln), that each
      produce adendritic melanocytes. Suppression is due to the ability of dsu to
      partially restore (ash and ln), or almost completely restore (d), normal
      melanocyte morphology. While the ash and ln gene products have yet to be
      identified, the d gene encodes a novel myosin heavy chain (myosin 12), which is
      speculated to be necessary for the elaboration, maintenance, and/or function of
      melanocyte cell processes. To begin to discriminate between different models of
      dsu action, we have produced aggregation chimeras between mice homozygous for dsu
      and mice homozygous for d to determine if dsu acts cell autonomously or cell
      nonautonomously. In addition, we have further refined the map location of dsu in
      order to examine a number of possible dsu candidate genes mapping in the region
      and to provide a genetic basis for the positional cloning of dsu.

PMID- 7828831
TI  - Comparative mapping of Arabidopsis thaliana and Brassica oleracea chromosomes
      reveals islands of conserved organization.
AB  - The chromosomes of Arabidopsis thaliana and Brassica oleracea have been
      extensively rearranged since the divergence of these species; however, conserved
      regions are evident. Eleven regions of conserved organization were detected,
      ranging from 3.7 to 49.6 cM in A. thaliana, spanning 158.2 cM (24.6%) of the A.
      thaliana genome, and 245 cM (29.9%) of the B. oleracea genome. At least 17
      translocations and 9 inversions distinguish the genomes of A. thaliana and B.
      oleracea. In one case B. oleracea homoeologs show a common marker order, which is
      distinguished from the A. thaliana order by a rearrangement, indicating that the
      lineages of A. thaliana and B. oleracea diverged prior to chromosomal duplication
      in the Brassica lineage (for at least this chromosome). Some chromosomal segments
      in B. oleracea appear to be triplicated, indicating the need for reevaluation of
      a classical model for Brassica chromosome evolution by duplication. The
      distribution of duplicated loci mapped for about 13% of the DNA probes studied in
      A. thaliana suggests that ancient duplications may also have occurred in
      Arabidopsis. The degree of chromosomal divergence between A. thaliana and B.
      oleracea appears greater than that found in other confamilial species for which
      comparative maps are available.

PMID- 7828832
TI  - Possible loss of length conservation and reciprocity during recombination or
      conversion in tandem arrays.
AB  - Recombination or conversion between arrays of repeated sequences need not be
      conservative for length because two single strands of DNA from one chromatid may
      form heteroduplexes in different registers on the other participating duplex.
      This can cause an overall change in repeat number. Loss of length conservation is
      equally possible whether models of recombination initiated by single-strand
      transfer or double-strand break are applicable. Length changing conversion will
      frequently produce a characteristic insertion within a deletion, often appearing
      as a double deletion such as are frequently found in new variants of human
      minisatellite MS32. There is no apparent means of preserving parity during length
      changing conversion or recombination, and if the changes are biased then the
      overall copy number will increase or decrease according to that bias. The
      observation that arrays persist suggests that any bias in these arrays will be
      toward gains. An equilibrium may be reached where gains, which may be largely
      independent of array length, equal losses from the array-length-dependent
      processes of intrachromatid recombination and repeated unequal sister chromatid
      exchanges.

PMID- 7828833
TI  - Dynamics of genetic variability in two-locus models of stabilizing selection.
AB  - We study a two locus model, with additive contributions to the phenotype, to
      explore the dynamics of different phenotypic characteristics under stabilizing
      selection and recombination. We demonstrate that the interaction of selection and
      recombination results in constraints on the mode of phenotypic evolution. Let Vg
      be the genic variance of the trait and CL be the contribution of linkage
      disequilibrium to the genotypic variance. We demonstrate that, independent of the
      initial conditions, the dynamics of the system on the plane (Vg, CL) are
      typically characterized by a quick approach to a straight line with slow
      evolution along this line afterward. We analyze how the mode and the rate of
      phenotypic evolution depend on the strength of selection relative to
      recombination, on the form of fitness function, and the difference in allelic
      effect. We argue that if selection is not extremely weak relative to
      recombination, linkage disequilibrium generated by stabilizing selection
      influences the dynamics significantly. We demonstrate that under these
      conditions, which are plausible in nature and certainly the case in artificial
      stabilizing selection experiments, the model can have a polymorphic equilibrium
      with positive linkage disequilibrium that is stable simultaneously with
      monomorphic equilibria.

PMID- 7828834
TI  - Epistasis can facilitate the evolution of reproductive isolation by peak shifts:
      a two-locus two-allele model.
AB  - The influence of epistasis on the evolution of reproductive isolation by peak
      shifts is studied in a two-locus two-allele model of a quantitative genetic
      character under stabilizing selection. Epistasis is introduced by a simple
      multiplicative term in the function that maps gene effects onto genotypic values.
      In the model with only additive effects on the trait, the probability of a peak
      shift and the amount of reproductive isolation are always inversely related,
      i.e., the higher the peak shift rate, the lower the amount of reproductive
      isolation caused by the peak shift. With epistatic characters there is no
      consistent relationship between these two values. Interestingly, there are cases
      where both transition rates as well as the amount of reproductive isolation are
      increased relative to the additive model. This effect has two main causes: a
      shift in the location of the transition point, and the hybrids between the two
      alternative optimal genotypes have lower average fitness in the epistatic case. A
      review of the empirical literature shows that the fitness relations resulting in
      higher peak shift rates and more reproductive isolation are qualitatively the
      same as those observed for genes causing hybrid inferiority.

PMID- 7828835
TI  - Homology of p53 intronic sequences between four laboratory mouse strains and
      Japanese wild mouse (Mus musculus molossinus Mishima).
AB  - Strain variation in the mouse p53 gene sequences was investigated in various
      regions of the gene in 14 inbred strains of laboratory mice and one Japanese wild
      mouse strain (Mus musculus molossinus Mishima, M. MOL-MSM). Nucleotides within
      p53 introns 1 and 7, found to be identical in 10 of the laboratory strains
      (129/J, A/J, AKR/J, BALB/cJ, C3H/HeJ, C57BL/6J, CBA/J, CE/J, NZB, and SWR/J),
      were substituted for other nucleotide sequences in common with M. MOL-MSM and the
      four other strains (DBA/1J, DBA/2J, I/LnJ, and P/J). The latter were documented
      to have originated from a common ancestor. These observations thus suggested the
      possibility that the p53 gene may have become substituted by outcrossing of this
      ancestral strain with Asian mice; this is presumably related to the documentation
      that Japanese mice brought to western countries were used as laboratory mice
      early in this century. To establish p53 gene heterozygosity, female C3H/HeJ and
      male DBA/2J mice were mated to produce F1 hybrids (C3D2F1). Electrophoresis of
      PCR fragments including polymorphic regions with or without restriction enzyme
      digestion, allowed clear distinction of paternal and maternal p53 alleles. These
      markers, therefore, should be useful for studying the loss of heterozygosity of
      the p53 gene during the carcinogenic process.

PMID- 7828836
TI  - Some evidence of incipient speciation in Drosophila kikkawai.
AB  - Altogether 11 geographic populations of Drosophila kikkawai were analysed from
      the viewpoint of karyotypic variation, inversion polymorphism and sexual
      isolation. The results revealed that of all the populations, the New Guinea
      population was the most genetically diverged, characterized by its distinct
      karyotype, possession of a fixed inversion, and its females exhibiting sexual
      isolation at the level of preferential mating. Based on these findings it was
      inferred that incipient speciation has proceeded in D. kikkawai and its New
      Guinea population is on its way to speciation.

PMID- 7828837
TI  - In pursuit of a molecular mechanism for adaptive mutation.
AB  - An unexpected way of making mutations in bacteria has challenged concepts of the
      genetic mechanisms behind evolution for the past 6 years. Work on the molecular
      mechanism of these so called "adaptive" mutations is rapidly revealing a
      surprising and novel molecular mechanism, and it is altering our understanding of
      how mutations form in nondividing cells.

PMID- 7828838
TI  - Genetic polymorphism between and within Meloidogyne species detected with RAPD
      markers.
AB  - Genetic analyses were conducted on root-knot nematode populations belonging to
      the four major species of the genus Meloidogyne and originating from many
      countries throughout the world. Discrete genetic markers used in this study were
      random genomic DNA sequences amplified by the polymerase chain reaction (RAPD).
      Primers of 17-30 nucleotides with 30-55% G + C content were tested. Five of them
      generated a total of 74 scorable markers that provided reliable polymorphisms
      both between and within species. Using RAPD patterns alone or in combination, all
      the Meloidogyne species and populations studied could be unambiguously
      discriminated. Based on the presence or absence of bands, maximum-parsimony
      analysis of the data resulted in clustering of species and populations congruent
      with previous isoenzymatic and molecular data. The resulting tree confirmed the
      early divergence of M. hapla from the other species and also that M. arenaria is
      closer to M. javanica than it is to M. incognita. The boot-strap analysis
      significantly supported most of the specific branching observed in the topology
      but did not identify the three M. arenaria populations as a monophyletic group.

PMID- 7828839
TI  - A genetic map of common bean to localize specific resistance genes against
      anthracnose.
AB  - A bean genetic map was developed to locate resistance genes against anthracnose
      and genes involved in plant defense mechanisms. One hundred and fifty-seven
      markers (51 restriction fragment length polymorphism, 100 random amplified
      polymorphic DNA, 2 sequence characterized amplified regions, and 4 morphological
      markers) were used to construct a genetic map covering 567.5 cM of the bean
      genome. Morphological markers consisted in two resistance genes towards
      anthracnose (Are and RVI), a dominant gene for nuclear male sterility (Ms8) and a
      pod-shape character (SGou). This map was established by using a backcross
      population (BC1) of 128 individuals, derived from a cross between two European
      bean genotypes: Ms8EO2 and Corel. Nine percent of the markers showed segregation
      distortions and mapped to three regions. Clusters of 2-10 markers were observed
      in every linkage group. The possible origin of these clusters is discussed.
      Nineteen markers shared with a previously published bean linkage map allowed us
      to establish a preliminary correspondence between the two maps. Finally, seven
      genes involved in plant defense mechanisms were located on this map.

PMID- 7828840
TI  - Centromeric heterochromatin and satellite DNA in the Chironomus plumosus species
      group.
AB  - Species of the Chironomus plumosus group display significant differences in their
      amount of centromeric heterochromatin. A tandem-repetitive satellite-like DNA has
      been isolated from C. plumosus. This DNA accounts for a major part of the
      centromeric heterochromatin. The DNA element has a Sau3AI restriction site ("Sau
      elements") and a monomer length of 165 or 166 bp. It is A-T rich (73%) and
      reveals a moderate DNA curvature, as shown by gel migration and computer
      analysis. The chromosomal localization and genomic organization of Sau elements
      were studied in 24 Chironomus species by in situ hybridization and (or) Southern
      analysis. The DNA is predominantly located in the centromeric regions of nine
      species, six from the plumosus group and three others. In some cases, inter- and
      intra-specific differences in the size of the centromeric heterochromatin seem to
      correlate with the strength of Sau element hybridization signals. Few species
      contain Sau repeats outside of the centromeres (C. borokensis, C. plumosus).
      Additionally, Sau elements are revealed to be present in ectopic threads between
      centromeres, and in B chromosomes found in C. borokensis and C. annularius.

PMID- 7828841
TI  - Cytotaxonomic differentiation of the afrotropical Drosophila montium subgroup: D.
      diplacantha and D. seguyi. The major role of reverse tandem duplications.
AB  - Aiming to establish phylogenetic relationships among species of the montium
      subgroup, detailed polytene chromosome maps are given showing intraspecific
      polymorphism and ecdysone induced larval puffing pattern profiles of two
      Afrotropical members of this subgroup, Drosophila diplacantha and D. seguyi. Both
      species exhibit two unique characteristics that define the montium subgroup,
      namely, a large number of reverse tandem duplications and a progressive darkening
      of anterior spiracles of the late third instar larvae, which is accompanied by a
      definite temporal and spatial puffing pattern of the salivary gland chromosomes.
      In contrast with the well-formed Balbiani ring 1 (BR1) observed in Oriental and
      Indian montium species, BR1 exhibits a different developmental profile in D.
      diplacantha, while it is obscured in D. seguyi. Although phyletic comparisons of
      five species from five different complexes within the subgroup show some
      conservation in banding and puffing pattern homologies, an analysis to assign map
      sections by sequential rearrangements remains unresolved at this time. The
      evolution of the subgroup is discussed in relation with the sharing of reverse
      tandem duplications, especially those including the montium BRs.

PMID- 7828842
TI  - Ultrastructural banding induced by DraI or HaeIII progressive digestion and in
      situ nick translation on human chromosomes.
AB  - Fixed human metaphase chromosomes were progressively digested with DraI or HaeIII
      restriction enzymes, submitted to in situ nick translation, and observed by
      transmission electron microscopy to obtain further information on the
      localization of the endonuclease target sequences and on the conformational
      changes in chromosomal bands. This approach allows us to detect specific nick
      translation patterns, namely, G-banding or R-like banding after short DraI and
      HaeIII endonuclease digestion, respectively. Intermediate banding recognizable as
      C-negative banding and G + C banding are induced by longer HaeIII digestion,
      before the C-positive banding. These patterns appear to depend both on different
      target sites of the employed endonucleases and on the DNA loss at different
      digestion times.

PMID- 7828843
TI  - A mid-arm interchange as a potential reproductive isolating mechanism in the
      medically important Simulium neavei group (Diptera: Simuliidae).
AB  - The Simulium neavei group is medically important as a vector of human
      onchocerciasis and is unique among blackflies because of the attachment to
      freshwater crabs during parts of the larval and pupal life cycle stages. Detailed
      larval salivary gland polytene chromosome maps are presented for two taxa
      designated S. neavei Amani form A and S. neavei Amani form B, which are probably
      synonymous with the previously described morphospecies, S. nyasalandicum and S.
      woodi, respectively. Simulium neavei Amani form B differs from S. neavei Amani
      form A by three paracentric inversions, a large deletion and a chromocentre,
      while the latter taxon differs from the former one by a mid-arm interchange. The
      fixed mid-arm interchange (1-tr) between two related taxa is unique among the
      Simuliidae. Detailed banding analysis of S. neavei Amani form B shows that,
      relative to S. neavei Amani form A, sections 16a, 16b, and 17c of the short arm
      of chromosome one (IS) have been inserted into section 69/70 of the short arm of
      chromosome three (IIIS). Assignment of directionality for this interchange
      inferred because of the near universality in the Simuliidae of a chromosome III
      long arm to short arm ratio of 2:1. We propose that the mid-arm interchange acted
      as a primary isolating mechanism because of the segregational load on F1
      heterozygous interchange progeny. The magnitude of the segregational load would
      be dependent on the frequency of pairing and crossing-over between the transposed
      interstitial segment and its original counterpart in the chromosome complement.
      Nonpairing in the transposed region and normal random segregation would
      presumably lead to a 50% of gametes carrying the duplicated or deficient
      transposed segment, resulting in a segregation load of 50%. However, crossing
      over in the paired interstitial region may greatly increase segregational load as
      result of multivalent formation at metaphase one (MI) and the generation of
      dicentric bridge(s) and acentric fragment(s) upon cell division. Such meiotic
      disjunction irregularities could lead to meiotic arrest, gametic loss and (or)
      cell restitution, and the eventual formation of polyploid (lethal) zygotes.

PMID- 7828844
TI  - Occurrence and inheritance of microsatellites in Pinus radiata.
AB  - Microsatellites are an important class of DNA marker because of their abundance
      and length hypervariability. As part of a project mapping the Pinus radiata
      genome, we have characterized some of the microsatellites in this species.
      Southern blots were screened with oligonucleotide probes [(CA)10, (GA)10, (GAA)9,
      (CAA)8, (CAC)5, (GACA)4] to assess their abundance. CA and GA were the most
      abundant microsatellites, while GAA was least abundant. A genomic library in
      lambda ZAP, covering 9 x 10(4) kb, was screened with a combined poly(CA) +
      poly(GA) probe and yielded 120 positives, approximately one CA or GA
      microsatellite every 750 kb of the P. radiata genome. It was found that 25% of
      the positives were embedded within highly repetitive DNA. Four of the five
      subclones sequenced contained compound microsatellites, with TA predominating as
      the additional repeat. Segregation analysis of PCR products for two
      microsatellites, PR4.6 and PR9.3, in 96 progeny of a controlled outcross verified
      simple Mendelian inheritance. Both loci are highly polymorphic with Polymorphism
      Information Content values of 0.63 and 0.70 for PR4.6 and PR9.3, respectively.
      These results indicate that microsatellites are abundant in a conifer genome and
      can be valuable markers for pine mapping, fingerprinting, and population genetic
      studies.

PMID- 7828845
TI  - The in situ localization of Adh transcripts in Drosophila species reveals evolved
      regulatory differences in spatially restricted expression.
AB  - Spatial and temporal aspects of Adh expression were examined during oogenesis and
      embryogenesis of Drosophila melanogaster, D. simulans, and D. virilis by in situ
      hybridization. In stage 14 and 15 embryos, differences in zygotic expression of
      Adh in the primordia of the gastric caecae of D. simulans and in the fat body of
      D. virilis were observed. These zygotic differences appear to be transient
      because Adh expression is seen in the gastric caecae of stage 16 embryos of D.
      simulans and in the fat body of stage 17 embryos of D. virilis. Analysis of D.
      melanogaster x D. simulans hybrids revealed that the parental difference for
      transcriptional activity of Adh in the primordia of the gastric caecae is under
      dominant control. These results provide the basis for exploring evolved
      regulatory differences in Adh expression during oogenesis and embryogenesis of
      Drosophila, which are until now unexplored. The potential of in situ
      hybridization in analyzing evolved regulatory differences in gene expression is
      briefly discussed.

PMID- 7828846
TI  - The molecular diversity of the 5S rRNA gene in barley (Hordeum vulgare).
AB  - The 5S rRNA genes from several accessions of cultivated barley, Hordeum vulgare
      L., were amplified by the polymerase chain reaction, cloned, and sequenced.
      Analysis of the aligned sequences, followed by principal coordinate analysis,
      support the recognition of at least two distinct classes of 5S rDNA genes. The
      short repeat class corresponds to the 300-bp tandem repeat defined by E.V.
      Ananiev as containing several TAG repeating units. The long repeat class contains
      long tandem repeats and lacks the TAG repeating unit. Sequences in each class can
      be further subdivided, with the long repeat class containing two groups and the
      short repeat class containing two and possibly three groups. These results
      suggest that in cultivated barley the sequence diversity found within the 5S rDNA
      nontranscribed spacer region may be encoded by three or more loci and may be
      useful for phylogenetic analyses provided that orthology can be established.

PMID- 7828847
TI  - Genetic interaction between hoxb-5 and hoxb-6 is revealed by nonallelic
      noncomplementation.
AB  - hoxb-5 and hoxb-6 are adjacent genes in the mouse HoxB locus and are members of
      the homeotic transcription factor complex that governs establishment of the
      mammalian body plan. To determine the roles of these genes during development, we
      generated mice with a targeted disruption in each gene. Three phenotypes
      affecting brachiocervicothoracic structures were found in the mutant mice. First,
      hoxb-5- homozygotes have a rostral shift of the shoulder girdle, analogous to
      what is seen in the human Sprengel anomaly. This suggests a role for hoxb-5 in
      specifying the position of limbs along the anteroposterior axis of the vertebrate
      body. Second, hoxb-6- homozygotes frequently have a missing first rib and a bifid
      second rib. The third phenotype, an anteriorizing homeotic transformation of the
      cervicothoracic vertebrae from C6 through T1, is common to both hoxb-5- and hoxb
      6- homozygotes. Quite unexpectedly, hoxb-5, hoxb-6 transheterozygotes (hoxb-5
      hoxb-6+/hoxb-5+ hoxb-6-) also show the third phenotype. By this classical genetic
      complementation test, these two mutations appear as alleles of the same gene.
      This phenomenon is termed nonallelic noncomplementation and suggests that these
      two genes function together to specify this region of the mammalian vertebral
      column.

PMID- 7828848
TI  - drifter, a Drosophila POU-domain transcription factor, is required for correct
      differentiation and migration of tracheal cells and midline glia.
AB  - The Drosophila drifter (dfr) gene, previously referred to as Cf1a, encodes a POU
      domain DNA-binding protein implicated as a neuron-specific regulator in the
      developing central nervous system (CNS). We have isolated full-length dfr cDNA
      clones that encode a 46-kD protein containing the conserved POU-domain DNA
      binding domain. The use of alternate polyadenylation sites produces two dfr mRNA
      transcripts that are first expressed in stage 10 embryos at 5- to 6-hr of
      development. A specific anti-dfr polyclonal antiserum generated against a dfr
      glutathione S-transferase fusion protein recognizes a 46-kD protein on Western
      blots and has been used to analyze the cell-specific distribution of dfr protein
      during embryonic development. dfr protein is distributed in a complex expression
      pattern including the tracheal system, the middle pair of midline glia, and
      selected CNS neurons. We have carried out a genetic characterization of the dfr
      locus, previously localized to region 65D of the third chromosome, by generating
      a series of overlapping deficiencies between 65A and 65E1 that were used to
      isolate dfrE82, an EMS-induced lethal allele. Analysis of dfrE82 mutant embryos
      shows a disruption of the developing tracheal tree as well as commissural defects
      in the developing CNS. Based on an examination of a cell-specific marker for
      tracheal cells and midline glia, these defects appear to be caused by a failure
      of these cells to follow their characteristic routes of migration. The dfrE82
      tracheal phenotype is rescued by a dfr minigene present as a P-element transposon
      expressing wild-type dfr protein in tracheal cells. These results suggest that
      the dfr protein plays a fundamental role in the differentiation of tracheal cells
      and midline glia possibly by regulating the expression of essential cell-surface
      proteins required for cell-cell interactions involved in directed cell
      migrations.

PMID- 7828849
TI  - Identification of a novel serine/threonine kinase and a novel 15-kD protein as
      potential mediators of the gamma interferon-induced cell death.
AB  - Programmed cell death is often triggered by the interaction of some cytokines
      with their cell surface receptors. Here, we report that gamma interferon (IFN
      gamma) induced in HeLa cells a type of cell death that had cytological
      characteristics of programmed cell death. In this system we have identified two
      novel genes whose expression was indispensable for the execution of this type of
      cell death. The rescue was based on positive growth selection of cells after
      transfection with antisense cDNA expression libraries. The antisense RNA-mediated
      inactivation of the two novel genes protected the cells from the IFN-gamma
      induced cell death but not from the cytostatic effects of the cytokine or from a
      necrotic type of cell death. One of those genes (DAP-1) is expressed as a single
      2.4-kb mRNA that codes for a basic, proline-rich, 15-kD protein. The second is
      transcribed into a single 6.3-kb mRNA and codes for a unique 160-kD calmodulin
      dependent serine/threonine kinase (DAP kinase) that carries eight ankyrin
      repeats. The expression levels of the two DAP proteins were selectively reduced
      by the corresponding antisense RNAs. Altogether, it is suggested that these two
      novel genes are candidates for positive mediators of programmed cell death that
      is induced by IFN-gamma.

PMID- 7828850
TI  - Disruption of retinoblastoma protein function by coexpression of its C pocket
      fragment.
AB  - The growth suppression function of the retinoblastoma protein (RB) is mediated by
      its interaction with a variety of cellular proteins. RB contains at least two
      protein-binding pockets: the large A/B pocket, which interacts with E2F and the D
      type cyclins, and the C pocket, which interacts with the nuclear c-Abl tyrosine
      kinase. The large A/B pocket and the C pocket are shown here to be functionally
      distinct and can be occupied simultaneously. A complex containing E2F, RB, and c
      Abl is detected in vivo and can be assembled in vitro. We propose that the
      biological activity of RB not only depends on the inhibition of its targets but
      also on its ability to properly assemble specific protein complexes. Consistent
      with this hypothesis, a fragment of RB, SE delta, containing only the C pocket is
      shown to act as a dominant-negative inhibitor of RB function. SE delta does not
      have growth inhibitory activity of its own. When coexpressed with full-length RB,
      SE delta does not disrupt the RB-E2F or RB-D2 complexes nor does it affect the
      expression, phosphorylation, or nuclear tethering of the full-length RB. SE delta
      does compete with RB for binding to c-Abl and is fully capable of inhibiting the
      c-Abl tyrosine kinase. Thus, SE delta can inactivate RB while maintaining the
      inhibition of E2F and c-Abl. These results suggest that the inhibition of RB
      binding proteins is not sufficient to suppress cell growth and that the assembly
      of RB-mediated protein complexes is also important for the promotion of cell
      cycle arrest.

PMID- 7828851
TI  - Cloning of yeast HAP5: a novel subunit of a heterotrimeric complex required for
      CCAAT binding.
AB  - The CCAAT-binding factor is a conserved heteromeric transcription factor that
      binds to CCAAT box-containing upstream activation sites (UASs) within the
      promoters of numerous eukaryotic genes. The CCAAT-binding factor of Saccharomyces
      cerevisiae activates the transcription of these genes in response to growth in a
      nonfermentable carbon source. Previous studies have demonstrated that the HAP2,
      HAP3, and HAP4 subunits of the yeast CCAAT-binding factor are required for the
      transcriptional activation of genes containing a CCAAT box. Using the two-hybrid
      screening method, we have identified an additional component of the CCAAT-binding
      factor. We present the identification and characterization of a novel gene, HAP5,
      that encodes an additional subunit of the CCAAT-binding factor required for the
      assembly and DNA-binding activity of the complex. In a hap5 mutant, we show that
      CCAAT-binding activity is abolished in vitro. Furthermore, we demonstrate that
      purified recombinant HAP2, HAP3, and HAP5 are able to reconstitute CCAAT-binding
      activity in mobility shift analysis. These data suggest that the HAP2/3/5
      heterotrimer represents a unique DNA-binding factor in which all three subunits
      of the complex are absolutely required for DNA-binding activity.

PMID- 7828852
TI  - An unusual sequence arrangement in the telomeres of the germ-line micronucleus in
      Tetrahymena thermophila.
AB  - The ciliated protozoan Tetrahymena thermophila contains two nuclei that differ
      dramatically in function, chromosome size and number, chromatin structure, and
      mode of division. It is possible that the telomeres of the two nuclei have
      different functions. Although macronuclear telomeric DNA has been well
      characterized and consists of tandem G4T2/C4A2 repeats that are synthesized by
      the enzyme telomerase, micronuclear telomeres have not been isolated previously.
      Here, we report the identification and cloning of micronuclear telomeres and
      demonstrate that although they contain the same terminal tandem G4T2 repeats as
      macronuclear telomeres, they are strikingly different in three respects. First,
      the tracts of G/C-rich telomeric repeats are approximately seven times longer in
      the micronucleus than in the macronucleus (approximately 2.0-3.4 vs.
      approximately 0.3-0.5 kb, respectively) from the same cell population. Second,
      the immediate telomere-associated sequences (TASs) from six different
      micronuclear chromosome ends have an unusually high G/C content and degree of
      homology to one another, unlike macronuclear TASs. The TAS from at least one
      micronuclear chromosome is unique to micronuclear telomeres and is not present in
      the macronucleus. Finally, and unexpectedly, all micronuclear telomere clones
      contain an inner homogeneous tract of a variant G4T3 repeat adjacent to the
      distal tract of G4T2 repeats. The native micronuclear telomeric DNA is composed
      of approximately 30% G4T3 repeats, corresponding to 0.6-1.0 kb per average
      telomere, positioned centromere-proximally to most or all of the G4T2 repeats.
      Neither the G4T3 sequence nor any other variant repeat is found in macronuclear
      telomeres. Furthermore, such a homogeneous tract of a variant repeat has not been
      found in the telomeres of any eukaryote.

PMID- 7828853
TI  - CPSF recognition of an HIV-1 mRNA 3'-processing enhancer: multiple sequence
      contacts involved in poly(A) site definition.
AB  - The endonucleolytic cleavage and polyadenylation of a pre-mRNA in mammalian cells
      requires two cis-acting elements, a highly conserved AAUAAA hexamer and an
      amorphous U- or GU-rich downstream element, that together constitute the "core"
      poly(A) site. The terminal redundancy of the HIV-1 pre-mRNA requires that the
      processing machinery disregard a core poly(A) site at the 5' end of the
      transcript, and efficiently utilize an identical signal that resides near the 3'
      end. Efficient processing at the 3' core poly(A) site, both in vivo and in vitro,
      has been shown to require sequences 76 nucleotides upstream of the AAUAAA
      hexamer. In this report we demonstrate that this HIV-1 upstream element interacts
      directly with the 160-kD subunit of CPSF (cleavage polyadenylation specificity
      factor), the factor responsible for the recognition of the AAUAAA hexamer. The
      presence of the upstream element in the context of the AAUAAA hexamer directs the
      stable binding of CPSF to the pre-mRNA and enhances the efficiency of poly(A)
      addition in reactions reconstituted with purified CPSF and recombinant poly(A)
      polymerase. Our results indicate that the dependence of HIV-1 3' processing on
      upstream sequences is a consequence of the suboptimal sequence context of the
      AAUAAA hexamer. We suggest that poly(A) site definition involves the recognition
      of multiple heterogeneous sequence elements in the context of the AAUAAA hexamer.

PMID- 7828854
TI  - The DIMINUTO gene of Arabidopsis is involved in regulating cell elongation.
AB  - We have isolated a recessive mutation named diminuto (dim) from T-DNA transformed
      lines of Arabidopsis thaliana. Under normal growth conditions, the dim mutant has
      very short hypocotyls, petioles, stems, and roots because of the reduced size of
      cells along the longitudinal axes of these organs. In addition, dim results in
      the development of open cotyledons and primary leaves in dark-grown seedlings.
      The gene for DIM was cloned by T-DNA tagging. DIM encodes a novel protein of 561
      amino acids that possesses bipartite sequence domains characteristic of nuclear
      localization signals. Molecular and physiological studies indicate that the loss
      of-function mutant allele does not abolish the response of seedlings to light or
      phytohormones, although the inhibitory effect of light on hypocotyl elongation is
      greater in the mutant than in wild type. Moreover, the dim mutation affects the
      expression of a beta-tubulin gene, TUB1, which is thought to be important for
      plant cell growth. Our results suggest that the DIM gene product plays a critical
      role in the general process of plant cell elongation.

PMID- 7828855
TI  - Characterization of the Streptomyces peucetius ATCC 29050 genes encoding
      doxorubicin polyketide synthase.
AB  - The dps genes of Streptomyces peucetius, encoding daunorubicin (DNR)-doxorubicin
      (DXR) polyketide synthase (PKS), are largely within an 8.7-kb region of DNA that
      has been characterized by Southern analysis, and gene sequencing, mutagenesis and
      expression experiments. This region contains nine ORFs, many of whose predicted
      products are homologous to known PKS enzymes. Surprisingly, the gene encoding the
      DXR PKS acyl carrier protein is not in this region, but is located about 10 kb
      distant from the position it usually occupies in other gene clusters encoding
      type-II PKS. An in-frame deletion in the dpsB gene, encoding a putative subunit
      of the DXR PKS, resulted in loss of production of DXR and the known intermediates
      of its biosynthetic pathway, confirming that this gene and, by implication, the
      adjacent dps genes are required for DXR biosynthesis. This was verified by
      expression of the dps genes in the heterologous host, Streptomyces lividans,
      which resulted in the production of aklanonic acid, an early intermediate of DXR
      biosynthesis.

PMID- 7828856
TI  - Vectors with the fd replicon for in vivo cloning and analysis of genes.
AB  - We have constructed two new mini-Mu derivatives, pMRfP and pBEf, that combine the
      properties of known mini-Mu vectors and the advantages of the replication origin
      (orifd) of filamentous phage fd. Mini-Mu pMRfP consists of the left (850 bp) and
      the right (216 bp) ends of the Mu genome, orifd, packaging signal of fd, and the
      gene conferring resistance to chloramphenicol. The second mini-Mu, termed pBEf,
      carries the left end of Mu (1001 bp), which contains the so-called internal
      activation sequence (enhancer of transposition), required for a higher frequency
      of transposition, the right end (116 bp) and the gene conferring resistance to
      kanamycin. These new mini-Mu vectors are suitable for in vivo cloning with the
      ability of single-stranded DNA preparation using one of the helper phages
      (M13K07, rv1, IR1, R408) and with a large cloning capacity (the size of the
      cloned fragment can be up to 35 kb). They can also be used as the hoppers (a
      transposable ori that can be turned on or off depending on the presence of the fd
      gene 2 product). Thus, these mini-Mu derivatives can be employed as vectors for
      in vivo cloning, and as regulated transposons or mobile replicons.

PMID- 7828857
TI  - A new phage display system to construct multicombinatorial libraries of very
      large antibody repertoires.
AB  - We present an easy and efficient technique for the construction of large phage
      displayed antibody (Ab) repertoires through the recombination of two separate
      heavy (VH) and light (VL) chain gene libraries. Here, the system has been applied
      to the display of a chimpanzee anti-HIV gp160 Ab. The process, which makes use of
      lambda phage att recombination sites, leads to the irreversible physical
      association between plasmid and phagemid vectors carrying, respectively, VL and
      VH sequences. The heat-inducible expression of the Int recombinase allows perfect
      control of recombination. Selection of the recombinant phagemid is made possible
      by the assembly, in vivo, of a genetic marker (chloramphenicol resistance)
      created only after the correct recombination event. Theoretically, all possible
      associations between the VL and VH sequences should be obtained, and it should be
      possible to generate multicombinatorial libraries of close to 10(12) clones.

PMID- 7828858
TI  - Constrained peptide libraries as a tool for finding mimotopes.
AB  - The monoclonal antibody (mAb) KAA8 recognizes the peptide angiotensin II (AII).
      The KAA8 mAb was biopanned using two phage-displayed peptide libraries, one
      unconstrained, the other constrained by a disulfide bond. After several cycles of
      biopanning, both libraries showed enrichment for phage that bind KAA8. Phage
      isolated from the unconstrained library contain a consensus sequence that matches
      the sequence of AII. A consensus sequence was also identified from the
      constrained library that does not resemble the AII sequence, and represents a
      mimotope of AII. We have also demonstrated that monovalent phage display can be
      used to discriminate between modest and high-affinity binding peptides.

PMID- 7828859
TI  - Site-directed mutagenesis of double-stranded DNA by the polymerase chain
      reaction.
AB  - We have developed a facile procedure for rapid PCR-based site-directed
      mutagenesis of double-stranded DNA. Increasing the initial template concentration
      and decreasing the PCR cycles to 5-10 allows us to reduce the rate of undesired
      second-site mutations and dramatically increase the time savings. Following PCR,
      DpnI treatment is used to select against parental DNA molecules. The DpnI (target
      sequence 5'-Gm6ATC) is specific for methylated and hemimethylated DNA and is used
      to digest parental DNA and select for mutation-containing amplified DNA. DNA
      isolated from almost all common Escherichia coli strains is Dam methylated and
      therefore susceptible to DpnI digestion. Pfu DNA polymerase is used, prior to
      intramolecular ligation of the linear template, to remove any bases extended onto
      the 3' ends of the PCR product by Taq DNA polymerase. The recircularized vector
      DNA incorporating the desired mutations is transformed into E. coli. This method
      can be used independently of any host strain and vector.

PMID- 7828860
TI  - A novel plasmid series for in vitro production of phoA translational fusions and
      its use in the construction of Escherichia coli PhoE::PhoA hybrid proteins.
AB  - We have developed a series of vectors for easy construction of translational
      fusions with the phoA gene (encoding the periplasmic alkaline phosphatase, PhoA)
      in the three reading frames. One plasmid series carries a multiple cloning site
      (MCS) followed by a promoterless and leaderless 5'-truncated phoA ('phoA), which
      in turn is followed by a kanamycin-resistance-encoding gene (kan). Another
      plasmid series contains two identical inverted MCS flanking the phoA-kan cluster.
      These latter vectors are devised as phoA-kan cassette delivery vectors. In-frame
      cloning results in the production of hybrid PhoA proteins which display PhoA
      activity if successfully exported beyond the cytoplasmic membrane. In order to
      test these vectors, we have constructed hybrid PhoE::PhoA proteins, which were
      used to analyze the activity of the phoE promoter and identify the hybrid gene
      products.

PMID- 7828861
TI  - Use of the tetracycline promoter for the tightly regulated production of a murine
      antibody fragment in Escherichia coli.
AB  - A generic vector, pASK75, was developed for the synthesis of foreign proteins in
      Escherichia coli under transcriptional control of the tetA promoter/operator.
      Tight regulation was achieved by placing the structural gene for the tet
      repressor, as a transcriptional fusion, downstream from the beta-lactamase
      encoding gene (bla) on the same plasmid. Strong expression of the foreign gene
      was conveniently induced by adding anhydrotetracycline at a low concentration.
      Using the production of a recombinant murine immunoglobulin F(ab) fragment as an
      example, the system was shown to function independently of the host-strain
      background and to be extremely well repressed in the absence of the inducer.
      Thus, it represents an economic and independent alternative to IPTG-inducible
      promoter constructs. Additional features of pASK75 include a signal sequence and
      a multiple cloning site followed by a region encoding the Strep tag affinity
      peptide to facilitate purification of a bacterially produced protein.

PMID- 7828862
TI  - pOSEX: vectors for osmotically controlled and finely tuned gene expression in
      Escherichia coli.
AB  - Expression of the proU operon of Escherichia coli is directly proportional to the
      osmolarity of the growth medium. The basal level of proU transcription is very
      low, but a large increase is triggered by a sudden rise in the external
      osmolarity. This increased expression is maintained for as long as the osmotic
      stimulus persists. We have capitalized upon these regulatory features of the proU
      operon and have constructed a series of expression vectors (pOSEX) permitting
      osmotically controlled expression of heterologous genes governed by regulatory
      signals of proU. The pOSEX vectors carry the proU promoter, an upstream region
      required for high-level expression, and part of the first structural gene (proV),
      which acts as a silencer and is necessary to maintain low-level expression in low
      osmolarity media. An extended multiple cloning site (MCS) positioned at the 3'
      end of proV' permits the cloning of heterologous genes into the pOSEX plasmids,
      and efficient transcription terminators derived from the rrnB operon prevent
      deleterious read-through transcription into the vector portion. The properties of
      the pOSEX expression vectors were tested by positioning a promoterless lacZ
      (encoding beta-galactosidase) gene from E. coli and the gcdA (encoding
      carboxytransferase) gene from the Gram+ bacterium Acidaminococcus fermentans
      under the control of the proU regulatory region. Efficient, osmo-regulated and
      finely tuned expression of both lacZ and gcdA was achieved, and the amount of
      beta-galactosidase and carboxytransferase synthesized were simply controlled by
      adjusting the osmolarity of the growth medium with various concentrations of
      NaCl.

PMID- 7828863
TI  - A small, high-copy-number vector suitable for both in vitro and in vivo gene
      expression.
AB  - A 2433-bp, high-copy-number expression vector, pUK, was constructed from pUC19
      and pKK223-3. The genes encoding chicken adenylate kinase (AK) and phospholipase
      A2, cloned into pUK, were highly expressed in vitro using the coupled
      transcription/translation system of Zubay. High-level in vivo expression in
      Escherichia coli was also demonstrated for the AK gene cloned in this vector. The
      multiple cloning site (MCS) of pKK223-3 was preserved in pUK. In addition, three
      more sites in the MCS sequence, AccI, BamHI and SalI, were made unique for the
      convenience of cloning.

PMID- 7828864
TI  - Recombinant enrichment by exploitation of restriction sites with interrupted
      palindromes: design, synthesis and incorporation of zero-background linkers in
      cloning and expression vectors.
AB  - A universal approach for improving the efficiency of cloning through a selective
      enrichment of recombinants has been developed. This was achieved by using novel
      polylinkers or multiple cloning sites (MCS) termed zero-background linkers (ZBL).
      These MCS have short-cutter site(s) incorporated in the wobble portion of the
      recognition sequence of the long-cutter(s) in such a fashion that cloning at the
      short-cutter site disrupts the continuity of the long-cutter-specific sequence.
      Consequently, digestion of the ligation mixture with the long-cutter, prior to
      transformation, essentially eliminates the insert negative clones from
      transformants. The usefulness of such background removal has been illustrated
      through the design and synthesis of a model ZBL molecule and then its
      incorporation into various popular cloning and expression vectors. We demonstrate
      that replacement of the residing MCS of a vector with ZBL leads to enhanced
      cloning efficiency, as evidenced by the marked increase in the ratio of
      recombinants to non-recombinants. Such vector improvement is nearly universal as
      zero backgrounding is an add-on feature and can be adapted to practically any
      vector system, without having to alter the essential features of the parent
      vectors.

PMID- 7828865
TI  - Open reading frames flanking the peptidyl-tRNA hydrolase-encoding gene of
      Escherichia coli.
AB  - The nucleotide (nt) sequences flanking the peptidyl-tRNA hydrolase-encoding gene
      (pth) of Escherichia coli were determined and analyzed. A coding open reading
      frame (ORF-3), identified just downstream from pth, had a deduced amino acid (aa)
      sequence homologous to a family of GTP-binding proteins. We found discrepancies
      between the ORF-3 sequence from a plasmid clone used in previous studies and
      another one derived from Kohara's phage collection. Two putative genes, ORF-4 and
      ORF-2, were also found upstream from pth. ORF-4 could code for a 393-aa peptide
      homologous to membrane-bound proteins. The nt sequence between ORF-2 and pth
      revealed the existence of a CAP-binding site correctly positioned to regulate the
      expression of ORF-2.

PMID- 7828866
TI  - Primary structure of the speC gene encoding biosynthetic ornithine decarboxylase
      in Escherichia coli.
AB  - A 2.91-kb fragment of the Escherichia coli chromosome containing the speC gene,
      encoding biosynthetic ornithine decarboxylase (ODC) was sequenced. The speC gene
      is encoded by a 2133-bp ORF; the deduced amino-acid sequence contains 711
      residues whose predicted molecular mass is 79,505 Da.

PMID- 7828867
TI  - Characterization of the macromolecular synthesis (MMS) operon from Listeria
      monocytogenes.
AB  - The macromolecular synthesis (MMS) operon consists of three genes: rpsU, which
      encodes the S21 ribosomal protein in Bacillus subtilis (Bs), rpsU is replaced by
      orfP23 which encodes a protein of unknown function), dnaG, encoding the DNA
      primase involved in the initiation of chromosome replication, and rpoD, which
      encodes the principal sigma subunit of RNA polymerase. The operon was cloned in
      three segments from Listeria monocytogenes (Lm), initially using a probe designed
      from a highly conserved region of RpoD. Analysis of the nucleotide sequence
      revealed three genes: orfP17 (whose product, P17, is homologous to Bs P23), dnaG
      and rpoD. The Lm DnaG resembles the primase from Escherichia coli through the
      first two-thirds of the sequence. C-terminal similarity was observed between DnaG
      from Lm and Bs. Lm RpoD is similar to Bs SigA, shares identical DNA-binding
      domains with SigA, and is a member of the sigma 43 subgroup of the sigma 70
      family.

PMID- 7828868
TI  - Organization and sequence of the SalI restriction-modification system.
AB  - The organization and nucleotide (nt) sequences were determined for the genes
      encoding the SalI restriction and modification (R-M) system (recognition sequence
      5'-GTCGAC-3') from Streptomyces albus G. The system comprises two genes, salIR,
      coding for the restriction endonuclease (ENase, R.SalI; probably 315 amino acids
      (aa), a predicted M(r) of 35,305; product, G'TCGAC) and salIM, coding for the
      methyltransferase (MTase, M.SalI; probably 587 aa, a predicted M(r) of 64,943;
      product, GTCGm6AC). The genes are adjacent, they have the same orientation, and
      they occur in the order salIR then salIM. R.SalI contains a putative magnesium
      binding motif similar to those at the active sites of R.EcoRI and R.EcoRV, but
      otherwise it bears little aa sequence similarity to other ENases. M.SalI is a
      member of the m6A gamma class of MTases. In aa sequence it resembles M.AccI,
      another m6A gamma-MTase whose recognition sequence includes the SalI recognition
      sequence as a subset.

PMID- 7828869
TI  - Isolation, sequence and characterization of the maltose-regulated mlrA gene from
      the hyperthermophilic archaeum Pyrococcus furiosus.
AB  - The mlrA (maltose regulated) gene from the hyperthermophilic archaeum Pyrococcus
      furiosus was identified from a family of clones whose expression was influenced
      by the presence of maltose in the medium. Sequencing of the 2276 bp of DNA
      containing mlrA and flanking regions revealed a 753-amino-acid (aa) (88 kDa) open
      reading frame (ORF). The ORF is preceded by a bacterial-like ribosome-binding
      site. The deduced product shared extensive homology with pyruvate dikinases (PDK)
      from both eukaryal and eubacterial sources (35-61% similarity) and the signature
      domains characteristic of this class of proteins were present. Northern blot
      experiments demonstrated the presence of an approx. 2.4-kb transcript in P.
      furiosus extracts, corresponding in length to that expected from expression of
      mlrA. P. furiosus cultures grown in the presence of maltose were found to contain
      approx. 5-10-fold greater mlrA mRNA than those grown without maltose. Initiation
      of transcription under both cultural conditions occurred at the same
      transcription start point (tsp), 23 bp downstream from a putative BoxA promoter
      element.

PMID- 7828870
TI  - Sequence of the DNA ligase-encoding gene from Thermus scotoductus and conserved
      motifs in DNA ligases.
AB  - By dideoxynucleotide sequencing of a genomic clone, we have determined the
      complete nucleotide sequence of the gene encoding NAD(+)-dependent DNA ligase (EC
      6.5.1.2) of the thermophilic bacterium Thermus scotoductus. The gene encodes a
      674-amino-acid thermostable enzyme highly similar to other bacterial DNA ligases
      and to parts of the deduced gene product of Escherichia coli ORF f562, 5' to the
      spoR gene encoding 5' guanosyl kinase.

PMID- 7828871
TI  - The gyrB gene lies opposite from the replication origin on the circular
      chromosome of Mycoplasma capricolum.
AB  - Using oligodeoxyribonucleotide primers and the polymerase chain reaction, we
      cloned and sequenced a 3.2-kb region which contains the gyrB gene, encoding the
      beta-subunit of gyrase from Mycoplasma capricolum. We localized gyrB opposite
      from the chromosomal replication origin (ori) of M. capricolum by genomic
      Southern hybridization.

PMID- 7828872
TI  - A Coxiella burnetii gene encodes a sensor-like protein.
AB  - Two-component regulatory systems play important roles in the adaptive responses
      of many bacteria to environmental changes. The sensor proteins of these systems
      are highly conserved near their C-termini. We exploited this feature to isolate a
      gene encoding a putative sensor component from the obligate intracellular
      rickettsial parasite Coxiella burnetii (Cb). Using degenerate primers and the
      polymerase chain reaction (PCR), we isolated a DNA fragment from a genomic
      library of Cb containing an open reading frame (ORF), sufficient to encode a 48
      kDa protein. Sequence comparison revealed that the deduced protein shared high
      homology to members of the bacterial sensor protein family, particularly at three
      conserved regions of the C terminus. When the Cb sensor-like gene was cloned into
      a high-copy-number vector and introduced into an E. coli strain (phoM, phoR), the
      mutant expressed low levels of alkaline phosphatase activity, suggesting that the
      gene functioned as a sensor protein in E. coli. Consequently, we designated this
      gene qrsA (for Q fever agent regulatory sensor-like gene). Because two-component
      regulatory systems have been implicated in a variety of cellular processes,
      including virulence determinants in some pathogenic bacteria, the identification
      of qrsA in Cb may shed light on how the pathogen adapts to extracellular changes
      during infection, as it proliferates in the phagolysosome.

PMID- 7828873
TI  - Sequence analysis of the Rickettsia prowazekii gyrA gene.
AB  - The Rickettsia prowazekii (Rp) gyrA gene, which codes for a subunit of DNA gyrase
      in this obligate intracellular bacterium, has been isolated and characterized.
      Nucleotide sequence analysis revealed an open reading frame (ORF), initiating
      with a GTG start codon, of 2718 bp that could encode a protein of 905 amino acids
      (aa) with a calculated M(r) of 101,048. The Rp gyrase subunit A (GyrA), when
      compared to GyrA analogs of other bacterial species, exhibited 43 to 50%
      identity. Alignment of the Rp GyrA aa sequence with the other analogs revealed
      the presence of a span of additional aa within the putative DNA-binding domain.
      The lack of an ORF within 865 bp upstream from the Rp gyrA demonstrates a Rp gene
      organization different from that of characterized gyrA from other species.
      Despite the similarity to Escherichia coli GyrA, Rp GyrA did not complement an E.
      coli gyrA temperature-sensitive mutant. However, Rp gyrA was dominant to an E.
      coli gyrA96 nalidixic-acid-resistant (NalR) mutant, conferring Nal sensitivity
      when introduced into the NalR E. coli strain.

PMID- 7828874
TI  - YKE2, a yeast nuclear gene encoding a protein showing homology to mouse KE2 and
      containing a putative leucine-zipper motif.
AB  - The nucleotide sequence of YKE2, a yeast nuclear gene, has been determined. The
      deduced YKE2 protein has 114 amino acids (12 kDa), shows significant homology
      with the murine KE2 and contains a putative Leu-zipper motif characteristic of a
      group of DNA-binding proteins [Landschulz et al., Science 240 (1988) 1759-1764].
      Strains in which YKE2 has been disrupted show normal cell growth in glucose and
      galactose media over the temperature range of 16 to 40 degrees C. Disrupted
      strains also display normal mating and sporulation abilities. Northern analysis
      revealed that the transcription of YKE2 is unresponsive to catabolite repression
      by glucose.

PMID- 7828875
TI  - The MID2 gene encodes a putative integral membrane protein with a Ca(2+)-binding
      domain and shows mating pheromone-stimulated expression in Saccharomyces
      cerevisiae.
AB  - The MID2 gene whose defect (the mid2-1 mutation) results in mating-pheromone
      induced death in Saccharomyces cerevisiae was cloned and its nucleotide (nt)
      sequence determined. The sequence showed an open reading frame (ORF) coding for a
      376-amino-acid (aa) protein with an estimated M(r) of 39,104, and six potential
      TATA boxes and two pheromone-response elements in its 5'-upstream region. The
      deduced aa sequence showed that the MID2 product (Mid2p) contains a putative N
      terminal signal sequence followed by a long Ser-rich region that could contain O
      glycosylation sites, a potential transmembrane domain and a conserved Ca(2+)
      binding domain, with the latter two located in the C-terminal half. Northern blot
      analysis showed that the expression of MID2 is stimulated threefold by mating
      pheromone. Cells that lack MID2 were able to grow normally, but died when exposed
      to mating pheromone, like the original mid2-1 mutant.

PMID- 7828876
TI  - Yeast expression vectors using RNA polymerase III promoters.
AB  - A series of Saccharomyces cerevisiae--Escherichia coli shuttle vectors is
      described in which small RNAs can be stably expressed in yeast from two different
      promoters for RNA polymerase III transcription. The vectors are available in
      either high- or low-copy-number forms with either URA3, HIS3, or TRP1 selection
      markers, and are based on a previously described set of plasmid vectors [Sikorski
      and Hieter, Genetics 122 (1989) 19-27]. Transcripts have structured pre-tRNA or
      RPR1 leaders fused to RNA corresponding to inserted sequences. Levels of RNA
      accumulation are dependent on plasmid copy number and the type of transcript.

PMID- 7828877
TI  - The Schizosaccharomyces pombe pka1 gene, encoding a homolog of cAMP-dependent
      protein kinase.
AB  - We have isolated 16 independent Schizosaccharomyces pombe cDNA clones that
      suppress the temperature-sensitive (ts) phenotype of a Saccharomyces cerevisiae
      strain containing the dominant-negative RAS2val19ala22 allele. Fourteen of these
      cDNAs encode Sz. pombe Ras1. The other two clones encode the C-terminal region of
      a protein we have named Pka1. We have cloned the pka1 gene from a Sz. pombe
      genomic library. It contains an uninterrupted open reading frame encoding a 512
      amino-acid (aa) protein. The C-terminal region (aa 200-512) of Pka1 is 51-63%
      identical to cAMP-dependent protein kinase (Pka) catalytic subunits from other
      eukaryotes. Production of Pka1 suppresses the ts phenotypes exhibited by Sa.
      cerevisiae ras1-ras2ts or cyr1ts strains. Furthermore, overproduction of Pka1 in
      Sz. pombe results in a sterile phenotype and an abnormal morphology similar to
      that exhibited by cells in which the cAMP pathway is constitutively activated.
      These observations suggest that pka1 encodes the Sz. pombe Pka catalytic subunit.

PMID- 7828878
TI  - The compositional compartments of the nuclear genomes of Trypanosoma brucei and
      T. cruzi.
AB  - Fractionation of DNA from Trypanosoma brucei and T. equiperdum by centrifugation
      in a Cs2SO4/BAMD density gradient indicated that these genomes are
      compositionally compartmentalized, a conclusion confirmed by the analysis of the
      compositional distribution of third codon positions from T. brucei and T. cruzi.
      In order to investigate whether this compartmentalization is accompanied by the
      often different properties of coding sequences, we have analyzed and compared the
      compositional compartments with respect to dinucleotide frequency and amino-acid
      usage of the encoded proteins of all gene sequences available in the GenBank
      database from T. brucei and T. cruzi. In all cases, the compartments displayed
      remarkable differences. These results are similar to findings obtained in highly
      compartmentalized genomes, like those of warm-blooded vertebrates.

PMID- 7828879
TI  - Sequence, transcript characterization and polymorphisms of a Plasmodium
      falciparum gene belonging to the heat-shock protein (HSP) 90 family.
AB  - A gene (pfhsp86) encoding a member of the heat-shock protein 90 (HSP90) family
      has been isolated from Plasmodium falciparum (Pf). The pfhsp86 coding region
      comprises two exons separated by an 0.8-kb intron with consensus splice junction
      sequences. The transcript itself is 3.4-kb long and includes a 0.65-kb 5'
      untranslated region (UTR) and a 0.54-kb 3'-UTR. Upstream of the transcription
      start point (tsp) are putative promoter modules: an inverted CCAAT box, a G + C
      rich sequence and several TATA sequences. Transcription is enhanced in in
      erythrocyte-stage parasites cultivated at elevated temperatures (2-3-fold at 39
      degrees C and 3-4-fold at 41 degrees C). The pfhsp86 gene maps within a
      chromosome 7 segment that is linked to chloroquine (Cq) response in a Pf cross.
      The parents of this cross (Dd2, HB3) differ in the first exon by two
      trinucleotide repeats, while more divergence is apparent between the introns.
      These trinucleotide repeat differences are linked to Cq response in the HB3 x Dd2
      cross, but they did not predict Cq response in nine Pf lines from different
      locations.

PMID- 7828880
TI  - Gene organization in the dnaA-gyrA region of the Streptomyces coelicolor
      chromosome.
AB  - The gene organization has been determined for an 8-kb portion of the Streptomyces
      coelicolor chromosome close to the origin of DNA replication (oriC).
      Hybridization and DNA sequence analyses revealed the presence of five open
      reading frames (ORFs) oriented in the same direction as the proximal dnaA and
      dnaN genes. The deduced products of three of the ORFs have been identified as the
      S. coelicolor homologs of RecF, GyrB and GyrA. These genes are usually clustered
      in the dnaA region of bacterial chromosomes. In S. coelicolor however, the usual
      gene arrangement is altered. The recF gene is flanked by two ORFs, one of which
      encodes a protein with significant similarity to 6-phosphogluconate
      dehydrogenases (6PGDH), an enzyme that is not immediately linked to DNA
      metabolism.

PMID- 7828881
TI  - Sequence of the macronuclear DNA encoding large subunit ribosomal protein 29
      (L29) in Euplotes crassus and cycloheximide sensitivity.
AB  - As a first step towards developing a DNA transformation method for the ciliated
      protozoan Euplotes crassus we determined the minimum inhibitory concentration
      (MIC) for cell division in the presence of cycloheximide (Chx) for several cell
      lines and the range of Chx sensitivity for 106 different progeny cell lines
      derived by mating two lines. All of the cell lines are highly sensitive to Chx.
      Progeny cell lines show a wider range of sensitivities than the parental lines.
      Because site-directed mutagenesis of the RPL29 gene encoding the large subunit
      ribosomal protein 29 (L29) has been used to generate a Chx-resistance marker
      (ChxR) for another ciliate, Tetrahymena thermophila [Yao and Yao, Proc. Natl.
      Acad. Sci. USA 88 (1991) 9493-9497], we isolated and sequenced the entire E.
      crassus macronuclear DNA carrying RPL29. The encoded peptide is 52-73% identical
      in sequence to L29 sequences from organisms ranging from T. thermophila and
      Saccharomyces cerevisiae to mouse. In E. crassus, the codon that has been mutated
      to confer Chx resistance in both S. cerevisiae and T. thermophila already encodes
      the amino-acid residue of one of the mutant forms identified in these other
      organisms. Thus, E. crassus RPL29 is not a convenient source of a selectable
      marker. Notable features of the macronuclear DNA carrying RPL29 are its extremely
      short non-coding regions and a TAG stop codon.

PMID- 7828882
TI  - Identification and analysis of a cuticular collagen-encoding gene from the plant
      parasitic nematode Meloidogyne incognita.
AB  - The vast majority of proteins in the nematode cuticle are collagens. Cuticular
      collagen-encoding genes (col) have been described for the animal parasites
      Ascaris suum and Haemonchus contortus and for the free-living Caenorhabditis
      elegans. The proteins encoded by all these genes seem to have the same basic
      structure, indicating that there is a conserved subfamily of cuticular col in
      these nematodes. In this paper, we describe the identification and
      characterization of a cDNA (Lemmi 5) which corresponds to a cuticular col of the
      plant-parasitic nematode Meloidogyne incognita. The derived protein structure is
      very similar to the basic structure of the C. elegans cuticular collagens. Using
      PCR technology, we have shown the presence of Lemmi 5-related sequences in the
      genome of Ditylenchus destructor. Our data strongly support the existence of a
      cuticular col subfamily which is highly conserved in the phylum Nemata.

PMID- 7828883
TI  - A Drosophila melanogaster homolog of the TIS11 family of immediate early genes
      that can rescue a cdr1 cdc25 mutant strain of fission yeast.
AB  - A Drosophila melanogaster (Dm) embryonic cDNA library was screened for genes
      capable of inhibiting wee1+/mik1+ protein kinase (Pk) function. We expected to
      identify homologs of the Schizosaccharomyces pombe gene nim1+. This gene encodes
      a Pk capable of phosphorylating and so inhibiting the wee1+ Pk that in turn
      inhibits p34cdc2. Dm cDNAs capable of complementing the temperature-sensitive
      phenotype of a nim1/cdr1 cdc25 double mutant strain were identified and found to
      fall into two classes. One class encodes the Dm Cdc2 protein. The second cDNA
      class encodes a novel protein containing a central motif consisting of two tandem
      repeats of a putative Zn(2+)-finger motif. This region is highly conserved in the
      TIS11 family of immediate early genes, which in mammalian cells are rapidly and
      transiently induced in response to 12-O-tetradecanoyl phorbol-13-acetate (TPA)
      and to mitogens such as epidermal growth factor and fibroblast growth factor.

PMID- 7828884
TI  - Three different calmodulin-encoding cDNAs isolated by a modified 5'-RACE using
      degenerate oligodeoxyribonucleotides.
AB  - In order to obtain the 5' ends of the three mouse calmodulin (CaM) cDNAs, we
      modified the standard 5' RACE (rapid amplification of cDNA ends) method to use
      degenerate synthetic oligodeoxyribonucleotides to prime cDNA synthesis of all
      three CaM mRNAs. In this modified method, the degenerate primers were annealed to
      mRNAs in an incubation step prior to the reverse transcription reaction.
      Separating the annealing step from the reverse transcription reaction allowed for
      greater stringency by using higher temperatures than could be tolerated if the
      reverse transcriptase were present. Annealing was also done with lower primer
      concentration and was driven by a longer incubation time. After the annealing
      step, cDNA synthesis was initiated by diluting the annealing mixture into a 42
      degrees C buffer with reverse transcriptase. The synthesized cDNA was poly(dA)
      tailed to allow PCR amplification of the first-strand cDNA with an anchor-dT17
      primer and the degenerate primers. The CaM cDNAs were evident after this PCR. A
      second PCR, with nested gene-specific primers, was used to isolate the individual
      CaM cDNAs from the products of the first PCR. Three distinct CaM cDNAs were
      cloned and sequenced. By comparison of the 5' untranslated sequences between the
      mouse CaM DNAs and rat CaM cDNAs, the corresponding homologs were assigned. The
      results suggest that application of this modified RACE method could improve the
      success of isolating specific cDNAs in cases where use of a nested primer is not
      possible or when amino-acid sequence information is available and only degenerate
      primers can be designed for cloning cDNAs by the 5'-RACE method.

PMID- 7828885
TI  - Cloning of the rat Gadd45 cDNA and its mRNA expression in the brain.
AB  - We cloned the rat Gadd45 (growth arrest and DNA damage inducible) cDNA and
      examined its mRNA induction by gamma-ray irradiation in the rat brain. The rat
      Gadd45 cDNA sequence was highly homologous to the previously published human and
      hamster cDNAs, and was partially similar to the 28S rRNA gene. The mRNA encoding
      rat GADD45 was induced in the brain after gamma-ray irradiation. This finding
      indicates that Gadd45 is an inducible gene following the ionizing radiation, not
      only in cultured cells in vitro, but also in animal tissues in vivo.

PMID- 7828886
TI  - The sequence of a cDNA encoding the major vault protein from Rattus norvegicus.
AB  - We have isolated a cDNA clone encoding the 104-kDa major vault protein (MVP) from
      Rattus norvegicus. The complete nucleotide sequence was determined. Comparison of
      the deduced amino acid (aa) sequence to that of MvpA from Dictyostelium
      discoideum revealed that the proteins share about 57% aa identity. Southern blot
      analysis indicates that the rat MVP is a single-copy gene.

PMID- 7828887
TI  - Hel-N2: a novel isoform of Hel-N1 which is conserved in rat neural tissue and
      produced in early embryogenesis.
AB  - Hel-N1 is a neural-specific RNA-binding protein which is highly conserved over
      evolution. The data presented here demonstrate alternative 5' splicing of Hel-N1
      mRNA, characterized by the insertion of a novel 91-bp exon. The resultant
      isoform, Hel-N2, has a potentially expanded N-terminal region of 29 amino acids
      when compared to Hel-N1. Reverse transcription (RT)-PCR cloning data indicate
      that homologues (Rel-N1 and Rel-N2) exist in rat neural tissue where there is 96%
      conservation at the nucleotide level. RT-PCR analysis of rat embryonic tissue RNA
      indicates that this splicing event occurs as early as day 12 of embryogenesis.
      The temporal pattern of expression of Rel-N1 and Rel-N2 resembles that of the
      Drosophila melanogaster homologue, elav, and supports the prior notion that these
      mammalian counterparts participate in early neural development.

PMID- 7828888
TI  - Alternative splicing of the mRNA encoding baboon glycoprotein receptor GPIIb.
AB  - The cloning and characterization of cDNAs encoding the cell-surface-specific
      integrin receptors of baboon platelets has been undertaken to provide species
      specific probes. These will be used to investigate the expression and
      distribution of these receptors among primate species. Clones GPIIb-16 and GPIIb
      3, encoding portions of the baboon glycoprotein GPIIb, were isolated from a cDNA
      library derived from baboon platelet mRNA. GPIIb-3 includes an insert of 43 bp,
      when compared to GPIIb-16 or human GPIIb. This insert is the result of
      alternative processing of mRNA. The probable origin of the inserted bases is the
      3' end of the intron preceeding exon 28 of the gene. A different product of
      alternative splicing has been reported in this same region of the human GPIIb
      sequence, suggesting that this location is susceptible to wobble in the intron
      exon junctions. The projected shift in the reading frame of the baboon GPIIb-3
      cDNA would give a radically altered C terminus of the deduced amino-acid
      sequence, and the possibility of a novel functional peptide on the platelet
      surface.

PMID- 7828889
TI  - Autonomous replication in vivo and in vitro of clones spanning the region of the
      DHFR origin of bidirectional replication (ori beta).
AB  - Plasmids containing the origin of bidirectional replication (ori beta) of the
      Chinese hamster dihydrofolate reductase-encoding gene (DHFR) were tested for
      autonomous replication in vivo and in vitro. The results show that plasmids pX24
      and pneoS13, that contain a 4.8- and a 11.5-kb fragment, respectively, spanning
      the ori beta region, are able to replicate autonomously in human cells and in a
      cell-free system that uses human cell extracts. Another plasmid, pX14, containing
      a 4.8-kb fragment that is immediately adjacent to the ori beta region, also
      replicated in these two assays.

PMID- 7828890
TI  - Cloning and analysis of human cDNAs encoding a 140-kDa brain guanine nucleotide
      exchange factor, Cdc25GEF, which regulates the function of Ras.
AB  - Ras proteins bound to GDP are biologically inactive while those bound to GTP are
      active. Ras-specific guanine nucleotide-exchange factors (GEFs) have been shown
      to activate Ras proteins. We used oligodeoxyribonucleotide primers with sequences
      similar to the cDNAs of rat and mouse cdc25 (encoding a Ras-GEF) to amplify, by
      the PCR, sequences with the potential to encode a 1275-amino-acid protein
      homologous to the rodent Cdc25GEF proteins. Northern blot analysis detected a
      brain-specific 5-kb transcript. We provide evidence for a novel alternately
      spliced transcript of cdc25 and show that these alternately spliced transcripts
      are differentially expressed in various regions of the adult nervous system.
      Antibodies raised against the C terminus of the protein recognize a 140-kDa
      protein in brain extracts of human, rat, guinea pig and cow; the 140-kDa protein
      is associated predominantly, if not exclusively, with a crude membrane fraction
      of brain. The C terminus of human Cdc25GEF can complement the loss of CDC25
      function in Saccharomyces cerevisiae. A glutathione S-transferase fusion protein
      containing the C terminus of the cdc25 product can stimulate guanine nucleotide
      exchange on H-Ras in vitro. Further, the Cdc25-fusion protein binds tightly to
      the nucleotide-free form of H-Ras in vitro, and this binding is reversed by the
      addition of GTP.

PMID- 7828891
TI  - Cloning of a cDNA encoding human ALDH7, a new member of the aldehyde
      dehydrogenase family.
AB  - Aldehyde dehydrogenases (ALDH; EC 1.2.1.3) are a family of isozymes which have
      been suggested to play a major role in the detoxification of aldehydes generated
      by alcohol metabolism and lipid peroxidation. Five non-allelic ALDH genes,
      encoding the ALDH1, 2, 3, 5 and 6 isozymes, have previously been identified and
      cloned in our laboratory. In this paper, we report the cloning and sequencing of
      a cDNA encoding a new human ALDH (ALDH7). Degenerate oligodeoxyribonucleotides
      derived from conserved regions of known ALDH cDNAs amplified a 408-bp product
      from human kidney total RNA by the reverse transcription-polymerase chain
      reaction (RT-PCR) procedures [Hsu et al., J. Biol. Chem. 266 (1992) 3030-3037].
      This PCR product was subcloned, selected and used as a probe to screen a human
      kidney cDNA library. The full-length human kidney cDNA (ALDH7) is 2791 bp in
      length and contains an open reading frame encoding 468 amino acids (aa). The
      deduced sequence of ALDH7 is longer than that of the human stomach ALDH3 by 15 aa
      at the C terminus. The degree of identity between the two isozymes is 52% with a
      positional alignment of 453 aa. Northern blot analysis demonstrated that lung is
      another major tissue expressing ALDH7.

PMID- 7828892
TI  - Cloning and sequences of the first eight genes of the chromosomally encoded
      (methyl) phenol degradation pathway from Pseudomonas putida P35X.
AB  - Pseudomonas putida P35X (NCIB 9869) metabolises phenol and cresols via a
      chromosomally encoded meta-cleavage pathway. A 13.4-kb fragment of the chromosome
      involved in encoding phenol catabolism was cloned and characterized. Deletion
      analysis and nucleotide sequencing of a 6589-bp region, in conjunction with
      enzyme assays, were used to identify the phhKLMNOP genes encoding the phenol
      hydroxylase, the phhB gene encoding catechol 2,3-dioxygenase (EC 1.13.11.2) and
      the phhQ gene that encodes a small ferredoxin-like protein. The genes are
      organised in an operon-like structure, in the order phhKLMNOPQB, and the deduced
      amino-acid sequences share high homology (68.3-99.7%) with those of the plasmid
      encoded genes dmpKLMNOPQB of Pseudomonas sp. strain CF600. Genetic evidence is
      presented that the difference in the growth substrate ranges of Pseudomonas P35X
      and CF600 are due to the effector activation specificities of the regulators of
      these systems, rather than the substrate specificities of the catabolic enzymes.

PMID- 7828893
TI  - Cloning of a cDNA encoding a novel human nuclear phosphoprotein belonging to the
      WD-40 family.
AB  - We have cloned and expressed in vaccinia virus a cDNA encoding an ubiquitous 501
      amino-acid (aa) phosphoprotein that corresponds to protein IEF SSP 9502 (79,400
      Da, pI 4.5) in the master 2-D-gel keratinocyte protein database [Celis et al.,
      Electrophoresis 14 (1993) 1091-1198]. The deduced aa sequence contains 9 Trp
      residues, some of which are localized in repeats and that characterise the
      protein as a member of the WD-40 family, a group of proteins having 40-aa repeats
      containing Trp and Asp [Duronio et al., Proteins 13 (1992) 41-56; Van der Voorn
      and Ploegh, FEBS Lett. 307 (1992) 131-134]. The protein contains a nuclear
      targeting signal (KKKGK), and fractionation of transformed human amnion cells
      (AMA) in karyoplasts and cytoplasts confirmed that it is predominantly localized
      in the nucleus. Database searching indicated that IEF SSP 9502 is a putative
      human homologue of the Saccharomyces cerevisiae periodic Trp protein, PWP1, a
      polypeptide that may play a regulatory role in cell growth and/or transcription.

PMID- 7828894
TI  - Cloning and characterization of the gene encoding the cGMP-phosphodiesterase
      gamma-subunit of human rod photoreceptor cells.
AB  - Rod photoreceptor cyclic GMP-phosphodiesterase (cGMP-PDE) is one of the key
      enzymes of the visual phototransduction cascade in the vertebrate retina. The
      holoenzyme is a heterotetrameric complex, consisting of two large catalytic
      subunits, alpha (88 kDa) and beta (84 kDa), and two identical inhibitory
      subunits, gamma (11 kDa). Here we present the complete nucleotide sequence of the
      gene (cGMP-PDE gamma) encoding the cGMP-PDE gamma-subunit from human rod
      photoreceptors. The transcribed region of the human cGMP-PDE gamma codes for a
      protein of 87 amino acids and consists of four exons interrupted by three
      introns. The first intron is located in the 5'-untranslated region. The 5'
      flanking region contains TATA-like and CAAT boxes which may serve as regulatory
      elements. The 5'-untranslated sequence (exon I) includes a potential SP1
      transcription factor-binding site (GC core hexanucleotide). In addition, there
      were five AluI repetitive elements found in the cGMP-PDE gamma, three in the
      first intron and two in the second intron.

PMID- 7828895
TI  - Biological activities and secondary structures of variant forms of human salivary
      cystatin SN produced in Escherichia coli.
AB  - Using an Escherichia coli expression system, pGEX-2T, that expresses foreign
      sequences as fusion proteins with a glutathione S-transferase (GST) carrier, we
      have produced several recombinant human salivary cystatin SN (reCsnSN) variants.
      These include a N-terminal-truncated form (aa 17-121), a C-terminal-truncated
      form (aa 1-102) and two deletion mutants (delta 12-16 and delta 56-60). A large
      amount of the insoluble fusion protein (approx. 15 mg/l) was produced in each
      case. These were solubilized with urea and refolded by dialysis. The GST carrier
      was then cleaved with thrombin and the reCsn variants (except delta 56-60) were
      purified by anion-exchange chromatography. The CysP inhibitory activities against
      papain, and bovine and human cathepsin B, and secondary structures of the reCsnSN
      variants were determined and compared to natural salivary CsnSN. The full-length
      reCsnSN, the N-truncated and the delta 12-16 variants inhibited the CysP activity
      of papain and displayed circular dichroism (CD) spectra similar to that of
      natural CsnSN. On the other hand, the delta 56-60 mutant and the C-truncated
      variant exhibited very little inhibitory activity towards papain. The CD spectrum
      of the C-truncated variant indicated a change in the secondary structure (e.g., a
      decrease in beta-sheet and an increase of an alpha-helical content). Neither, the
      natural nor the full-length reCsnSN or the delta 12-16 mutant exhibited any
      inhibitory activity towards bovine and human cathepsin B.

PMID- 7828896
TI  - Structural organisation and chromosomal mapping of the human Id-3 gene.
AB  - The helix-loop-helix (HLH) family of transcription factors plays a central role
      in the regulation of cell growth, differentiation and tumourigenesis. Members of
      the Id (inhibitor of DNA binding) class of these nuclear proteins are able to
      heterodimerise with and thereby antagonise the functions of other transcription
      factors of this family. We report here on the genomic organisation of the human
      Id3 (HLH 1R21/heir1) gene. Comparison with the two other mammalian Id genes, Id1
      and Id2, reveals a highly conserved protein coding gene organisation consistent
      with evolution from a common, ancestral Id-like gene. In addition, by using a
      yeast artificial chromosome (YAC) clone of Id3, we have fine-scale mapped the
      gene to chromosome band 1p36.1 by fluorescence in situ hybridisation (FISH) and,
      using the same FISH technique, we have detected heterogeneity in tumour
      associated 1p36 chromosome translocations.

PMID- 7828897
TI  - The human stromelysin promoter contains a previously unreported 1.0-kb sequence.
AB  - Cloning and characterization of the promoter region controlling the gene encoding
      human stromelysin (Str) has been previously reported [Quinones et al., J. Biol.
      Chem. 264 (1989) 8339-8344]. We have characterized independently isolated genomic
      clones of the STR promoter, designated pSKStrB and 682, that are considerably
      different from the published sequence. Although the sequences up to an XbaI site
      at -480 of the 5' regions are identical, a novel 1.0-kb segment exists upstream
      from -480. This sequence is absent from the published clone, but its presence in
      the genomic DNA from twelve individuals has been confirmed by both PCR analysis
      and restriction mapping. Upstream of the novel 1-kb segment, the sequence of the
      published clone reappears, but in pSKStrB exists in inverse orientation.

PMID- 7828898
TI  - Construction of human chromosome-3-specific radiation hybrids and
      characterization by Alu-PCR.
AB  - Using a modification of the procedure developed by Cox et al. [Genomics 4 (1989)
      397-407], we isolated and characterized 60 radiation hybrids (RH) prepared by
      fusing an X-ray-irradiated Chinese hamster-human chromosome 3 (Chr 3) cell line
      (Q314-2) with a UrdA Chinese hamster mutant cell line. The RH were screened for
      human DNA content by PCR amplification using primers directed to the human Alu
      repeat sequences. Over 80% (50/60) were scored as positive for the retention of
      human DNA. Of them, 18 were characterized with Chr-3-specific single-copy DNA
      probes of known map location. These experiments demonstrated that the RH analyzed
      contained distinct subregions of human Chr 3. The RH that we have produced
      constitute a bank of cellular clones containing small segments of Chr 3. In the
      accompanying paper [Atchison et al., Gene 151 (1994) 325-328], we present the
      construction of rare-restriction-site linking libraries and the sequence tagged
      site characterization of in situ localized clones.

PMID- 7828899
TI  - Construction of rare restriction site (NotI, SacII and ClaI) linking libraries
      and sequence-tagged site analysis of single-copy clones from a human chromosome-3
      specific library.
AB  - We have constructed rare restriction-site (NotI, SacII and ClaI) chromosome 3
      (Chr 3)-specific linking libraries in a plasmid-based vector by mass transfer of
      a lambda phage human Chr-3-specific library (LA03NS01-ATCC57717) into pUC18.
      Total plasmid DNA isolated from the plasmid-based Chr-3-specific library was
      digested with either ClaI, NotI or SacII. Linear molecules were separated from
      undigested circles by pulsed-field polyacrylamide-gel electrophoresis. Purified
      linear molecules were circularized with T4 DNA ligase and transformed into
      bacteria. The resulting clones were greatly enriched for sequences recognized by
      the original restriction endonuclease used for digestion (83 to 95%). These
      sublibraries are composed of 600 (NotI) 1000 (SacII) or 30,000 (ClaI) clones.
      Thus, this procedure allows for easy isolation of Chr-3-specific DNA clones
      containing a variety of rare restriction sites. Sequence-tagged site (STS) data
      are also presented for five site-specifically mapped Chr-3-specific DNA clones.
      These studies may facilitate the construction of region specific linking
      libraries for mapping of various disease-specific loci on Chr 3.

PMID- 7828900
TI  - Cloning cassettes containing the reporter gene xylE.
AB  - Two pUC-derived vectors containing the promoterless xylE gene (encoding catechol
      2,3-dioxygenase) of Pseudomonas putida mt-2 were constructed. The t(o)
      transcriptional terminator of phage lambda was placed downstream from the stop
      codon of xylE. The new vectors, pXT1 and pXT2, contain xylE and the t(o)
      terminator within a cloning cassette which can be excised with several
      endonucleases. When inserted into a transcribed sequence, this xylE cassette
      reports promoter activity and interrupts downstream transcription of the target
      sequence.

PMID- 7828901
TI  - Cloning of a full-length cDNA encoding the neutrophil-activating peptide ENA-78
      from human platelets.
AB  - Here we describe the cloning of a full-length cDNA encoding a neutrophil
      chemoattractant peptide, ENA-78, from human platelets. The cDNA encodes a
      predicted sequence of 114 amino acids and contains the Cys motif C-X-C found in
      other members of the alpha-chemokine family which also includes interleukin 8 (IL
      8). ENA-78 has a high degree of sequence identity with other platelet-derived
      chemokines which also share overlapping chemotactic activities such as GRO alpha
      and the neurophil-activating peptide 2 (NAP-2; derived by proteolytic cleavage of
      the connective-tissue-activating peptide III (CTAP-III)).

PMID- 7828902
TI  - Sequence of the gene encoding the N-terminal portion of the Plasmodium yoelii
      yoelii 17XL merozoite surface protein-1 (MSP-1).
AB  - The nucleotide (nt) sequence of the 5' portion of the gene encoding the
      Plasmodium yoelii yoelii (Pyy) 17XL merozite surface protein-1 (MSP-1) was
      determined by direct sequencing of both strands of the polymerase chain reaction
      (PCR) product. This report completes the entire coding region of the Pyy 17XL MSP
      1 gene which we have found to be identical to the nt sequence of the Pyy YM MSP-1
      [Lewis, Mol. Biochem. Parasitol. 36 (1989) 271-282], despite independent
      selection of parasite clones, passages and replications in mice over many years.

PMID- 7828903
TI  - Cloning of two rabbit GRO homologues and their expression in alveolar
      macrophages.
AB  - We cloned two rabbit GRO homologue cDNAs from a lipopolysaccharide-stimulated
      rabbit alveolar macrophage (AM) cDNA library. One cDNA contains the complete
      coding sequence for a new mature GRO protein, RabGRO, which shares 68, 78 and 70%
      amino-acid identity with human GRO-alpha, -beta and -gamma, respectively. The
      other cDNA contains previously unreported sequence encoding a second GRO protein,
      rabbit permeability factor 2. The two Rab GRO proteins share 93% identity.
      Northern analysis shows that Rab AM GRO expression is rapidly induced by
      lipopolysaccharide. These findings suggest that GRO chemokines may be important
      in the pulmonary inflammation that occurs with septic lung injury.

PMID- 7828904
TI  - Polymorphism of the gene encoding a human minimal potassium ion channel (minK).
AB  - A gene (minK) that encodes a minimal potassium channel has been cloned recently.
      We describe in this paper a human minK sequence which differs from the original
      sequence with a single A-->G at position 112. This resulted in a change from a
      Ser codon (AGT) to a Gly codon (GGT) and created a new MspAI restriction site. Of
      the 32 alleles from 16 subjects studied, 25 had this newly discovered sequence
      and 7 had the previously described sequence.

PMID- 7828905
TI  - The Bacillus subtilis pnbA gene encoding p-nitrobenzyl esterase: cloning,
      sequence and high-level expression in Escherichia coli.
AB  - p-Nitrobenzyl esters serve as protecting groups on intermediates in the
      manufacture of clinically important oral beta-lactam antibiotics; de
      esterification of the intermediates is required for synthesis of the final
      product. A Bacillus subtilis PNB carboxy-esterase (PNBCE) catalyzes hydrolysis of
      several beta-lactam antibiotic PNB esters to the corresponding free acid and PNB
      alcohol. This communication (i) describes cloning the pnbA gene, which encodes
      PNBCE, (ii) provides the nucleotide sequence of the pnbA open reading frame (ORF)
      and (iii) describes a method for efficiently expressing the ORF in Escherichia
      coli. The amino acid (aa) sequence, deduced from the nucleotide sequence of the
      pnbA ORF, matched an experimentally determined N-terminal aa sequence of B.
      subtilis PNBCE and also matched an active site sequence previously identified by
      biochemical analyses. Specific activity of PNBCE in crude extracts was more than
      90-fold greater in recombinant E. coli, as compared to B. subtilis. This increase
      in expression led to more than a 500-fold improvement in the efficiency of
      purification of PNBCE.

PMID- 7828906
TI  - Construction and characterization of M13 bacteriophages displaying functional IgG
      binding domains of staphylococcal protein A.
AB  - Staphylococcal protein A (SPA) is ranked as a versatile probe in immunoassays
      because of its immunoglobulin G (IgG)-binding capability. However, poor binding
      of SPA to the IgG of some laboratory animals and its inability to bind human IgG3
      restricts its universal utility. In the present study, DNA encoding the four IgG
      binding domains of SPA (E, D, A and B) or the B domain alone has been fused, in
      separate phagemid vectors, to the 5' end of gene 111 of the phage M13. Upon
      infection by helper phage M13KO7, phagemid particles encapsulating single
      stranded DNA were produced. Dot immunoblot and Western blot analyses showed the
      presence of fusion proteins on the M13 surface. Binding of rabbit IgG-horseradish
      peroxidase (IgG-HRP) complex to the phage particles confirmed that the fusion
      proteins possessed functional IgG-binding domains. The interaction of these
      phages with immobilised human IgG and its various subclasses was studied by the
      phage capture immunoassay where the captured phages were detected by a monoclonal
      antibody to the major coat protein encoded by gene VIII (gVIII). The phages
      showed maximal binding to IgG1 kappa, followed by IgG2 kappa, and showed
      negligible binding to the IgG3 kapa and IgG3 lambda subclasses. The specificity
      of IgG-binding phages was confirmed in a phage capture and elution assay where
      the binding of these phages to immobilised human IgG1 kapa weas abolished in the
      presence of excess of soluble protein A. Moreover, IgG-binding phages could be
      enriched approx. 1000-fold over non-specific phages in a single round of
      panning.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7828907
TI  - Characterization of the genome region encoding structural proteins of
      Lactobacillus delbrueckii subsp. lactis bacteriophage LL-H.
AB  - Two regions from the genome of the virulent Lactobacillus delbrueckii subsp.
      lactic bacteriophage LL-H were sequenced (2330 and 12939 bp; 44% of the 34.6-kb
      genome). Together with the previously sequenced region containing the major
      capsid protein-encoding gene (2498 bp), the sequence had 21 open reading frames
      (ORFs) on the main coding strand. Only two putative ORFs were detected on the
      complementary strand. The ORFs covered 93.2% of the sequence. All but four of the
      ORFs were preceded by a ribosome-binding site. Only four longer non-coding
      stretches of sequences (175-278 nucleotides (nt) in size) were present. The
      longest of the non-coding regions contained an A + T-rich sequence that is
      surrounded by eight perfect copies of an 8-nt sequence that is present both as
      direct and inverted repeats. This region could represent the origin of
      replication. All the previously mapped structural protein-encoding genes of phage
      LL-H were included in the sequence. Genes were identified for the following five
      proteins: gp19 (encoded by gene g17), gp58 (g71), gp61 (g57), gp75 (g70) and gp89
      (g88). N-terminal amino-acid sequencing was performed on gp19 and gp75, and it
      was found that the N-terminal Met had been post-translationally removed from both
      proteins.

PMID- 7828908
TI  - Cloning, characterization and expression of pepF, a gene encoding a serine
      carboxypeptidase from Aspergillus niger.
AB  - We have cloned a gene (pepF) encoding a serine carboxypeptidase, proteinase F
      (PEPF), from Aspergillus niger. The sequences were identified in a phage lambda
      genomic DNA library using a synthetic probe based on the N-terminal sequence of
      PEPF. Nucleotide sequence data from pepF genomic and cDNA clones reveals that it
      is composed of four exons of 199, 283, 227 and 881 bp, interrupted by three
      introns of 53, 69 and 59 bp. The sequence of pepF codes for a polypeptide of 530
      amino acids (aa), of which the first 52 aa are not present in the mature PEPF.
      This region may represent a prepro sequence that is removed by proteolytic
      cleavage as a monobasic cleavage site (Lys52). Northern blot analysis of total
      cellular RNA extracted from A. niger cells indicates that pepF is transcribed as
      a single 1.8-kb mRNA, which is regulated by nitrogen and carbon repression,
      specific induction and the pH of the culture medium.

PMID- 7828909
TI  - Cloning of the Xenopus laevis cdk2 promoter and functional analysis in oocytes
      and during early development.
AB  - CDK2 (cyclin-dependent kinase 2) is a serine/threonine kinase which is involved
      in regulating S-phase entry in higher eukaryotes. To investigate the
      transcriptional control of this gene, a 13-kb Xenopus laevis genomic clone
      containing the 5' flanking sequences was isolated. A 2.7-kb fragment containing
      the promoter region was sequenced and the transcription start point (tsp) was
      determined by primer extension. Several putative regulatory elements, such as the
      E2F-binding site, Y box and octamer-binding site, were localized in this region,
      but no TATA box was found. When fused to cat, a reporter gene encoding
      chloramphenicol acetyltransferase, the 5' flanking sequences were shown to
      function in oocytes and an enhancer activity was found in this region. During
      early embryogenesis, cdk2 promoter activity was tested and de novo transcription
      was detected at the mid-blastula transition.

PMID- 7828910
TI  - Evidence for adenine methylation within the mouse myogenic gene Myo-D1.
AB  - Previous studies have indicated that there may be uncleavable TaqI sites (TCGA)
      within the mouse myogenic gene, Myo-D1. Fragments of DNA bearing most of the
      presumed insensitive TaqI sites have been reproduced using PCR. The presence of
      each of the originally uncleavable TaqI sites has been confirmed and each TaqI
      site has been shown to be sensitive to TaqI hydrolysis in PCR-synthesized genomic
      DNA. Since TaqI is inhibited by methylation of the adenine residue within its
      recognition sequence (but not by cytosine methylation), it is suggested that
      specific adenine bases are methylated in the coding region of Myo-DI and
      maintained throughout cell division. The same TaqI recognition sequences are
      insensitive to digestion in genomic DNA isolated from various mouse tissues
      including fetus, regenerating skeletal muscle and a myogenic cell line, all of
      which express Myo-D1. Thus, adenine methylation is not a modification of DNA
      following gametic fusion nor does it appear to play a major role in regulation of
      Myo-D1 expression.

PMID- 7828911
TI  - Isolation of nested, bidirectional deletions by the use of exonuclease III on
      double-origin vectors.
AB  - When used in conjunction with double-origin vectors, the popular exonuclease III
      method can generate nested deletions from both ends of cloned DNA fragments. Such
      bidirectional deletions can be useful in sequencing long DNA fragments in both
      directions.

PMID- 7828912
TI  - Identification and characterization of a trans-activator involved in the
      regulation of encapsulation by Bacillus anthracis.
AB  - Production of the plasmid-pXO2-encoded capsule by Bacillus anthracis is required
      for full virulence of the organism. The induction of capsule synthesis in vitro
      requires growth in the presence of bicarbonate and CO2; however, little else is
      known about the regulation of capsule synthesis and the role it plays in the
      expression of virulence. Recently, transposon Tn917 mutagenesis of B. anthracis
      plasmid pXO2 identified genes involved in capsule production and genes associated
      with virulence in inbred mice. One mutant, UUP5, had an 8.2-kb deletion located
      outside of the capsule structural gene region (cap). UUP5 was reduced
      significantly in capsule production and in virulence as compared to the wild-type
      (wt) parental strain. Using a HindIII-generated pXO2 library, we examined
      fragments contained in the deleted region and showed that electroporation of the
      mutant with a cloned 2.3-kb HindIII fragment restored capsule production to wt
      levels. Sequence analysis of the 2.3-kb fragment revealed a 1449-bp open reading
      frame (ORF) encoding a 483-amino-acid (57 kDa) protein, in good agreement with
      the 55-kDa protein detected by in vitro transcription/translation. Construction
      of a frameshift mutant that replaced the 55-kDa protein with a truncated 34-kDa
      moiety abrogated the complementing activity of the fragment in UUP5. mRNAs
      specific for cap and for the 1449-bp ORF were detected in mutant UUP5 transformed
      with the unaltered fragment and grown in the presence of bicarbonate, but not in
      air. No cap-specific mRNA, and very low levels of ORF-specific mRNA, were
      detected in UUP5 containing the frameshift mutation.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7828913
TI  - A gene from the hyperthermophile Pyrococcus furiosus whose deduced product is
      homologous to members of the prolyl oligopeptidase family of proteases.
AB  - The mlr-2 gene from the hyperthermophilic archaeum Pyrococcus furiosus was
      identified from a family of clones whose expression was influenced by the
      presence of maltose in the medium. The sequence of 2100 bp of DNA containing mlr
      2 and its flanking regions revealed a 616-amino-acid (71 kDa) open reading frame
      (ORF). The ORF's initiation codon appeared 10 nt into the mlr-2 message and was
      not preceded by any apparent ribosome-binding site. The deduced product shared
      homology with prolyl endopeptidases from both eukaryotic and eubacterial sources
      (52-57% similarity, 30-37% identity) and signature domains containing the Ser-Asp
      His triad, which is characteristic of this family of proteases, were present.
      Northern blot experiments revealed the presence of an approx. 2.0-kb transcript
      in P. furiosus extracts, corresponding in length to that expected from mlr-2
      expression. Initiation of transcription occurred 23 bp downstream from a putative
      BoxA promoter element.

PMID- 7828914
TI  - Gene MRP-L4, encoding mitochondrial ribosomal protein YmL4, is indispensable for
      proper non-respiratory cell functions in yeast.
AB  - In order to characterize individual protein components of the mitochondrial (mt)
      ribosome for regulatory, functional and evolutionary studies, the yeast nuclear
      gene MRP-L4 (accession No. Z30582), coding for the mt ribosomal protein (MRP)
      YmL4, has been cloned using oligodeoxyribonucleotides (oligos) deduced from a
      partial amino acid (aa) sequence [Graack et al., FEBS Lett. 242 (1988) 4-8] as
      screening probes. MRP-L4 is located on chromosome XII and codes for a slightly
      basic protein of 319 aa. The first 14 aa have not been found in the mature
      protein, and putatively form a signal peptide that is cleaved off during or after
      mt import. YmL4 has an N terminus very rich in Pro residues, and at its C
      terminus contains four hydrophobic domains. YmL4 shows no significant sequence
      similarity to any other sequence from the databases. Gene disruption shows the
      MRP-L4 product to be indispensable for mt function in cells growing on non
      fermentable carbon sources. In contrast to nearly all other MRPs investigated so
      far, gene disruption of MRP-L4 also affects growth of yeast cells on fermentable
      carbon sources, suggesting additional cytosolic and/or mt functions of YmL4
      besides its involvement in mt protein biosynthesis.

PMID- 7828915
TI  - The ATP synthase (F1F0) of Streptomyces lividans: sequencing of the atp operon
      and phylogenetic considerations with subunit beta.
AB  - The DNA encoding the subunits of the ATP synthase (F1F0) of Streptomyces lividans
      66 strain 1326 was identified using oligodeoxyribonucleotide probes derived from
      the N-terminal sequence of subunit gamma of the F1 complex. The complete
      nucleotide sequence of the operon was determined. The atp operon contains nine
      genes, atpIBEFHAGDC, encoding the eight structural components of the ATP synthase
      complex and the i protein, a polypeptide of unknown function. The gene order
      found is identical to that in other non-photosynthetic eubacteria. The
      determination of the N-terminal amino acid (aa) sequences of the F1 subunits
      alpha, beta, gamma, delta and epsilon allowed us to identify the translational
      start points and to define the primary structures of the proteins. The aa
      sequence deduced for subunit delta revealed an N-terminal extension of about 90
      aa, which is not present in any delta subunit or OSCP (oligomycin sensitivity
      conferral protein) of other species studied so far. The phylogenetic relationship
      of eu- and archaebacteria was investigated using sequencing data of the highly
      conserved beta subunit of different ATP synthases including that of S. lividans.
      The calculations revealed that S. lividans beta does not form a phylogenetic
      group together with the Gram+ taxa of low G+C contents, but is more closely
      related to the beta subunit of Rhodobacteria.

PMID- 7828916
TI  - The respiratory system of Kluyveromyces lactis escapes from HAP2 control.
AB  - A functional homolog of the Saccharomyces cerevisiae HAP2 gene, coding for one
      element of a transcriptional activator complex, was cloned from the yeast
      Kluyveromyces lactis and its nucleotide sequence was determined. Inactivation of
      the gene had no significant effect on respiration-dependent growth, suggesting
      that the HAP2/3/4 complex has no major control over the formation of the
      mitochondrial respiratory system in K. lactis.

PMID- 7828917
TI  - Cloning and sequence of a gene encoding the pyruvate dehydrogenase E1 beta
      subunit of Schizosaccharomyces pombe.
AB  - A 4906-bp DNA fragment, which complemented Schizosaccharomyces pombe strains
      partly defective in pyruvate dehydrogenase (PDH), was cloned and sequenced. The
      fragment contained an open reading frame (ORF) of 366 amino acids (aa), which
      showed 62% identity with the Saccharomyces cerevisiae gene encoding the PDH E1
      beta subunit, and significant similarity to subunits from a number of other 2-oxo
      acid dehydrogenase complexes from mammals, Gram+ and some Gram- bacteria. The
      clone hybridised to a 1.6-1.7-kb mRNA from wild type, and the 5' ends of the mRNA
      were mapped 73-83 bp upstream from the AUG start codon of the ORF. No other ORFs
      were found in this 4.9-kb segment of the Sz. pombe genome. Plasmids containing
      the ORF complemented the PDH-defective strains of Sz. pombe both for growth and
      for enzyme activity.

PMID- 7828918
TI  - Analysis of the 3-phosphoglycerate kinase 2 promoter in Rhizopus niveus.
AB  - Promoter analysis was performed on the Rhizopus niveus 3-phosphoglycerate kinase
      2-encoding gene (pgk2), one of the two pgk genes (pgk1 and pgk2) from this
      filamentous fungus sequenced so far. Deletion mutants of the promoter region were
      fused to the Escherichia coli uidA gene (which codes for beta-glucuronidase;
      GUS), and introduced into R. niveus to measure the intracellular GUS activities
      of the transformants. Deletion of the sequence between nt -174 to -133 (numbers
      indicate the position from the putative translation start codon) caused a
      significant decrease in the ratio of the GUS activity of the transformant
      cultured in glucose medium compared to that in glycerol medium. In this region, a
      21-nt sequence which is well conserved between pgk1 and pgk2 is present. When it
      was inserted into the promoter region of the uninducible gene encoding RNase Rh
      of R. niveus, ligated in front of uidA and introduced into R. niveus, the GUS
      activity of the transformant was greatly induced by glucose, but less by
      glycerol. We therefore suggest that the 21-nt sequence is a glucose-inducible
      transcriptional activator of R. niveus. This is the first report on a
      transcriptional activator in zygomycetes.

PMID- 7828919
TI  - Compositional properties of nuclear genes from Plasmodium falciparum.
AB  - We have analyzed the compositional distributions of coding sequences and their
      different codon positions, as well as the codon usage of the nuclear genes of
      Plasmodium falciparum, a parasite characterized by an extremely GC-poor genome.
      As expected, coding sequences are AT-rich, codon usage is strongly biased towards
      A or T in third codon positions, and some particular amino acids (aa) are
      especially abundant in the encoded proteins. Remarkably, however, no difference
      was detected between housekeeping (HK) and antigen (Ag) genes, in spite of
      differences in expression level and evolutionary constraints. Moreover, all the
      features found in P. falciparum are very similar to those found in a bacterium
      characterized by a very GC-poor genome, Staphylococcus aureus. These findings
      stress the importance of compositional constraints in determining codon usage and
      aa utilisation.

PMID- 7828920
TI  - The ts15 mutation of Escherichia coli alters the sequence of the C-terminal nine
      residues of Rho protein.
AB  - The segment of the rho gene that harbors the ts15 mutation was isolated and
      sequenced. The mutation, an IS1 insertion, changed the sequence of the C-terminal
      nine amino-acid residues, altering seven and eliminating the last two.

PMID- 7828921
TI  - The deduced Vibrio cholerae RecA amino-acid sequence.
AB  - The nucleotide sequence of the recA gene of Vibrio cholerae (Vc) has been
      determined. The amino acid (aa) sequence of the protein product is very similar
      to other known RecA aa sequences. However, this sequence does not agree with a
      previously reported Vc RecA aa sequence [Ghosh et al., Nucleic Acids Res. 20
      (1992) 372].

PMID- 7828922
TI  - Production of a phosphorylated GST::HPV-6 E7 fusion protein using a yeast
      expression vector and glutathione S-transferase fusions.
AB  - A Saccharomyces cerevisiae GAL7 expression vector for the production of protein
      fusions to glutathione S-transferase (GST) has been constructed. Using this
      vector, a GST fusion to human papillomavirus type 6 (HPV-6) E7 protein was
      produced and purified by affinity chromatography in a single step, at a yield of
      2 micrograms/ml of culture. The E7 portion of the fusion protein was
      phosphorylated, in contrast to the same product made in Escherichia coli.
      Therefore, yeast GST vectors may be of specific use in producing phosphoproteins,
      or proteins with other eukaryotic post-translational modifications, in
      preparative amounts for in vitro analysis.

PMID- 7828923
TI  - A unique intron-containing hsp70 gene induced by heat shock and during
      sporulation in the aquatic fungus Blastocladiella emersonii.
AB  - We have isolated and characterized cDNA and genomic DNA clones encoding the 70
      kDa heat-shock protein (Hsp70) from the aquatic fungus Blastocladiella emersonii
      (Be). Nucleotide (nt) sequence analysis predicts an acidic protein containing 650
      amino acids, with a calculated molecular mass of 70.8 kDa. The Be hsp70 gene is
      induced by heat shock (HS), as well as during sporulation of the fungus, and its
      coding region is interrupted by a single intron. All the evidence seems to
      indicate that this is the only hsp70 in Be. S1 nuclease protection assays
      revealed that splicing of the hsp70 intron is highly thermoresistant; at the
      lethal temperature of 42 degrees C, only 30% of the hsp70 mRNAs have not been
      processed. A single transcription start point (tsp), localized about 30 nt
      downstream from a putative TATA box, was determined both during HS and at normal
      temperatures. The promoter region presented several NGAAN repeats (where N is any
      nucleotide) characteristic of HS elements, as well as putative binding sites for
      ATF, Sp1 and two metal-responsive elements.

PMID- 7828924
TI  - Comparisons of ribosomal RNA sequences from amitochondrial protozoa: implications
      for processing, mRNA binding and paromomycin susceptibility.
AB  - The amitochondrial (a-mt) protozoa include four groups of organisms that are of
      interest as important human parasites and as probable descendents of the earliest
      branches of eukaryotic evolution. These organisms have not been directly compared
      in terms of structure and function of a specific molecule. We sequenced portions
      of their rRNA-encoding genes coding for the internal transcribed spacers (ITS1
      and 2) and adjoining small subunit (SS), 5.8S and large subunit (LS) rRNAs.
      Included are sites for RNA processing, mRNA interaction and aminoglycoside
      binding, as well as potential protein-encoding genes. The ITS of all a-mt
      protozoa examined are relatively short, but otherwise diverse. They include one
      or two predominant nucleotides (A in Entamoeba and Trichomonas, T in
      Encephalitozoon and C in Giardia) and have minimal potential secondary structure,
      which may form the basis for the preferential processing of ITS sequences. The
      mechanism employed by a-mt protozoa to bind mRNA may be unique, since Giardia,
      Trichomonas and Entamoeba mRNAs have usually short 5' non-coding regions. In
      bacteria, the 3' terminus of the SS rRNA is involved in mRNA binding; analysis of
      Entamoeba and Trichomonas mRNA 5' non-coding sequences suggests an analogous
      mechanism involving potential base pairing to the loop of the terminal SS rRNA
      hairpin. Giardia sensitivity to paromomycin was previously correlated with the
      presence of a C:G bp near the decoding region of SS rRNA. This bp is also present
      in Entamoeba and Trichomonas, consistent with their susceptibility. Its absence
      in Encephalitozoon and other microsporidia predicts paromomycin resistance, and
      suggests a distinct evolutionary origin for this group.

PMID- 7828925
TI  - Functional phage display of ciliary neurotrophic factor.
AB  - We report the display of human ciliary neurotrophic factor (hCNTF), a survival
      factor for neuronal cells belonging to the alpha-helical cytokine superfamily, on
      the surface of the filamentous bacteriophage fd. The hCNTF cDNA was fused to a
      DNA sequence encoding the C-terminal domain of pIII, a minor coat protein exposed
      at one end of fd. Gene fusions were cloned into a plasmid containing the ColE1
      plasmid and fd origins of replication, and were packaged into phagemid particles
      upon superinfection with M13KO7 helper phage. The resulting fusion phage bound
      specifically to anti-CNTF antibodies and to the recombinant soluble CNTF alpha
      receptor. Moreover, phage-displayed hCNTF was found to possess biological
      activity at concentrations comparable to those of the soluble cytokine. These
      results demonstrate that CNTF can be displayed on phage in a correctly folded and
      functionally active form. Binding of fusion phage to immobilized CNTF alpha
      receptor and subsequent elution at low pH resulted in affinity purification of
      CNTF-displaying virions. Utilization of this technology should enable the
      selection of high-affinity variants from libraries of CNTF mutants displayed on
      phage.

PMID- 7828926
TI  - Specificity of the protein secretory apparatus: secretion of the heat-labile
      enterotoxin B subunit pentamers by different species of gram- bacteria.
AB  - The B-subunit pentamer(s) (EtxBp) of Escherichia coli heat-labile enterotoxin
      (LT) are secreted from Vibrio cholerae via the general secretion pathway (GSP),
      but remain periplasmic in E. coli. In order to determine if other Gram- bacteria
      were also able to secrete the ExtBp, the etxB gene, which encodes EtxB was
      introduced into different bacteria. Of the bacteria examined, most species of
      Vibrio and Aeromonas were able to secrete this protein through the outer
      membrane; other Gram- genera, including Erwinia, Klebsiella and Xanthomonas were
      not, even though they encode GSP genes homologous to those of V. cholerae. Thus,
      the ability to recognize the EtxBp as a secretable protein is confined to
      bacteria that were identified as being closely related to V. cholerae by
      examination of their 5S rRNA [MacDonell and Colwell, Syst. Appl. Microbiol. 6
      (1985) 171-182].

PMID- 7828927
TI  - Expression and identification of the strA-strB gene pair from streptomycin
      resistant Erwinia amylovora.
AB  - Deletions in either of the genes in the strA-strB gene pair of Erwinia amylovora
      plasmid pEa34 resulted in a dramatic decrease in streptomycin resistance (SmR),
      but SmR was restored to high levels by complementation. When strA and strB were
      cloned separately on a lacIq/Ptac-based expression vector in Escherichia coli,
      only the protein encoded by strA was produced. When a strong Shine-Dalgarno
      sequence was introduced and the start codon was located outside the double
      stranded region of the stable stem-loop, the protein encoded by strB was
      produced. Biochemical analysis of the respective phosphorylated products
      demonstrated that strA and strB encoded aminoglycoside-3"-phosphotransferase
      (APH(3")-Ib) and aminoglycoside-6-phosphotransferase (APH(6)-Id), respectively.
      These data suggest that the high-level SmR in bacteria containing strA and strB
      is due to the combined action of the two enzymes.

PMID- 7828928
TI  - Conservation of cis-acting elements within the tor regulatory region among
      different Enterobacteriaceae.
AB  - The Escherichia coli (Ec) torCAD operon encoding the trimethyl amine N-oxide
      (TMAO) reductase system is induced by both TMAO and anaerobiosis. The tor
      regulatory regions from bacteria related to Ec have been amplified by the
      polymerase chain reaction (PCR) using degenerate oligodeoxyribonucleotide primers
      based on conserved sequences of the tor products. The amplified regions from
      Salmonella enteritidis and Sa. typhimurium (St) were the same size as that from
      Ec and showed 82% identity with it. Interestingly, four boxes of a 10-nucleotide
      motif (5'-CTGTTCATAT) were found in direct repeat at the same location in the tor
      regulatory region of the three species. Although the amplified fragment from
      Shigella sonnei (Ss) was highly homologous to the Ec corresponding segment, the
      first tor box was missing. In Ec, the St and Ss tor promoters were still
      regulated by both TMAO and anaerobiosis, but their transcriptional activities
      were significantly lower than that of the Ec tor promoter. Deletion of the two
      first boxes of the Ec tor regulatory region inactivated the tor promoter while
      deletion of the region just upstream from the tor boxes led to a significant
      decrease in tor expression. Our results strongly suggest that the tor boxes, as
      well as specific sequences outside the tor boxes, play an important role in the
      expression of the tor operon.

PMID- 7828929
TI  - Cloning and characterization of the gene encoding an extracellular alkaline
      serine protease from Vibrio metschnikovii strain RH530.
AB  - The gene vapF, encoding VapT, one of the extracellular sodium dodecyl sulfate
      (SDS)-resistant alkaline serine proteases (Serp) from the Gram- Vibrio
      metschnikovii strain RH530 has been cloned in Escherichia coli. The recombinant
      E. coli produced a protease which co-migrated with VapT on gelatin polyacrylamide
      gels. The nucleotide (nt) sequence of the cloned vapT revealed a single open
      reading frame of 1641 bp encoding 547 amino acids (aa) (58,961 Da). Upon analysis
      of the N-terminal aa sequence, VapT was shown to be processed properly in
      recombinant E. coli and to consist of 428 aa (45,626 Da). The deduced aa sequence
      of VapT showed significant sequence homology to subtilisin Carlsberg from
      Bacillus licheniformis, particularly in the regions containing active site
      residues and calcium-binding sites. VapT had an intervening region of approx. 149
      aa between the His and Ser residues of the active site, as compared with other
      Serp.

PMID- 7828930
TI  - Similarity between the Rhizobium meliloti fliP gene and pathogenicity-associated
      genes from animal and plant pathogens.
AB  - The nucleotide sequence of the Rhizobium meliloti (Rm) fliP gene was determined.
      Rm strains carrying insertions within this gene were non-motile, lacked flagella
      and formed normal N2-fixing root nodules on alfalfa. The FliP protein showed
      similarity to several bacterial gene products involved in pathogenicity in both
      plant and animal pathogens. It is likely that all of these proteins share a
      common functional role in the secretion of specific proteins from bacterial
      cells.

PMID- 7828931
TI  - Expression of the subtilisin Carlsberg-encoding gene in Bacillus licheniformis
      and Bacillus subtilis.
AB  - The cloning and sequence of the 5' untranslated region (5'-UTR) of the Bacillus
      licheniformis (Bl) 6816 subtilisin Carlsberg gene (subC) are reported here. The
      5' and 3' ends of subC transcripts were characterized, and the promoter
      identified. Expression was studied using a fused lacZ reporter gene integrated
      into the chromosome of heterologous host Bacillus subtilis (Bs). beta Gal
      activities of mutants deleted within the promoter region identified a region
      which is required for stimulation by the transcriptional activator proteins, DegU
      and DegQ. This region is close to the transcription start point (tsp), and is
      adjacent to a sequence homologous to that involved in DegU/Q stimulation of the
      Bs subtilisin gene, aprE. Expression of subC in Bs was optimized by the use of
      heterologous promoter and by the deletion of UTR sequences predicted to be
      involved in secondary structures in the native subC mRNA. Sequence comparison
      with other subtilisin Carlsberg-type-encoding genes revealed a high degree of
      conservation of the entire 5'-UTR, including regulatory sequences and promoter,
      as well as part of the structural gene.

PMID- 7828932
TI  - The transformation frequency of plasmids into Bacillus anthracis is affected by
      adenine methylation.
AB  - Plasmids pLTV1 and pHV33, capable of replicating in both Gram+ and Gram-
      bacterial hosts (shuttle vectors), when derived from the Escherichia coli strain
      HB101, were inactive in an electro-transformation assay employing the Bacillus
      anthracis strains delta Ames-1 and delta V1B-1 as recipients. The same plasmids
      isolated from the DNA methyltransferase (MTase)-deficient E. coli strain GM2929
      (dam, dcm), were able to transform the B. anthracis strains at a frequency of
      10(2)-10(3) transformants/micrograms of plasmid DNA. Efficient transformation was
      also obtained when the plasmids were propagated in strains of B. subtilis 168
      (10(2)-10(4) transformants/micrograms of plasmid DNA). The B. subtilis strains
      used are known to harbor restriction/modification systems that recognize cytosine
      as a target for methylation. In contrast, no adenine methylation activities have
      been reported for these strains. The data presented indicate that DNA containing
      methylated adenine residues is restricted in the B. anthracis strains studied
      here, resulting in decreased plasmid DNA-mediated transformation frequencies.
      This inhibition could be alleviated by propagating plasmid species in MTase
      deficient (dam) strains of E. coli or B. subtilis 168, before their introduction
      into strains of B. anthracis.

PMID- 7828933
TI  - Analysis of genes encoding D-alanine:D-alanine ligase-related enzymes in
      Leuconostoc mesenteroides and Lactobacillus spp.
AB  - Degenerate oligodeoxyribonucleotides complementary to sequences encoding
      conserved amino acid (aa) motifs in D-alanine:D-alanine ligases (Ddl) were used
      to amplify approx. 600-bp fragments from glycopeptide-resistant strains of
      Leuconostoc mesenteroides (Lm), Lactobacillus plantarum, La. salivarius and La.
      confusus, and from a susceptible strain of La. leichmannii. Comparison of the
      deduced aa sequences of the PCR products revealed that the Ddl-related enzymes of
      resistant Lm and Lactobacillus spp. are more akin to each other (47-63% aa
      identity) than to that of susceptible La. leichmannii (33-37% aa identity),
      indicating that the Ddl-related enzymes in these intrinsically resistant species
      of Gram+ bacteria exhibit structural differences with those in susceptible
      species. The Ddl-related enzymes, VanA and VanB, implicated in acquired
      resistance to glycopeptides in enterococci, were not closely related to their
      counterparts in Lm and Lactobacillus spp., as they displayed only 26-32% aa
      identity.

PMID- 7828934
TI  - Production of Haemophilus influenzae type-b porin in Escherichia coli and its
      folding into the trimeric form.
AB  - The P2 protein from pathogenic Haemophilus influenzae type b (Hib) functions as a
      bacterial porin and is one of several immunogenic outer membrane proteins. The P2
      gene was expressed in Escherichia coli and the recombinant P2 protein (re-P2)
      purified to facilitate functional and immunologic studies. P2 was obtained from
      Hib strain Eagan using PCR and the pET vectors (17b and 11a) were used to produce
      re-P2 at levels exceeding 30% of the total E. coli proteins. Since previous
      reports had indicated that P2 was toxic to E. coli, steps were taken to control
      the toxicity. The plasmid was stabilized by tightly controlling the synthesis of
      re-P2 prior to induction. Subsequent to induction, re-P2 was sequestered into
      inclusion bodies rather than to membrane compartments. The refolding of the
      denatured re-P2 into the trimeric form involved high salt and calcium ions. re-P2
      was then purified to homogeneity using gel-filtration and ion-exchange
      chromatography.

PMID- 7828935
TI  - Cloning and sequencing of the Haemophilus influenzae exbB and exbD genes.
AB  - The exbB and exbD genes of Haemophilus influenzae (Hi) were cloned and sequenced.
      The deduced Hi ExbB and ExbD proteins possessed 27 and 28% amino-acid identity
      (56 and 58% relatedness) with the Escherichia coli ExbB and ExbD proteins,
      respectively; two proteins which function as TonB accessory proteins during
      biopolymer transport. Plasmid-encoded Hi exbB and exbD partially complemented an
      E. coli exbB/exbD mutation.

PMID- 7828936
TI  - Characterization of levJ, a sucrase/fructanase-encoding gene from Actinomyces
      naeslundii T14V, and comparison of its product with other sucrose-cleaving
      enzymes.
AB  - A library of Actinomyces naeslundii T14V DNA was constructed in plasmid pUC18 and
      from this several sucrose-positive clones were isolated. Evidence was obtained
      that all these clones contained the same gene. One clone, which carried a plasmid
      that was named pPNG102, was chosen for further study. It was found that the
      enzyme specified by this plasmid hydrolyzed sucrose, raffinose, inulin and levan,
      but not dextran, and did not synthesize fructan or glucan from sucrose. The
      sequence of the insert in pPNG102 was determined and was found to contain a large
      ORF that specifies a polypeptide of 99,319 Da with similarity to other sucrases.
      This gene was named levJ. The deduced amino acid (aa) sequence contained both a
      potential signal sequence and potential C-terminal cell envelope attachment
      domain. Alignments revealed an internal 331-aa domain not present in other
      levanases and sucrases. A neighbour-joining tree showed that sucrases of
      eukaryotic origin form a cluster with eubacterial sucrase/fructanases, and this
      cluster does not include other eubacterial sucrases. It is postulated that
      certain eukaryotic sucrase-encoding genes are of eubacterial origin.

PMID- 7828937
TI  - Cloning, sequencing and expression of the dnaJ gene of Coxiella burnetii.
AB  - A 6-kb EcoRI genomic DNA fragment of Coxiella burnetii, isolated from a
      recombinant bacteriophage lambda ZapII library, allowed heterologous genetic
      complementation of Escherichia coli deleted for its dnaJ gene. The C. burnetii
      dnaJ gene was expressed in E. coli and identified by Western blot analysis using
      polyclonal antibodies raised against purified E. coli DnaJ protein. Deletion
      mapping and genetic complementation demonstrated that C. burnetii dnaJ is present
      on a 2-kb EcoRI-HindIII genomic DNA fragment, from which the nt sequence of the
      C. burnetii dnaJ gene was determined.

PMID- 7828938
TI  - [Structure and level of basic food intake in adult working population of the
      Altai region].
AB  - Population of two Altai districts was found to consume insufficient amounts of
      food proteins, vegetable fats, some vitamins, and mineral substances.
      Recommendations on rationalization of nutrition of population were given.

PMID- 7828939
TI  - [Selenium in the food products of Ural economic region].
AB  - The main foodstuffs were tested for selenium levels in the Ural economical
      district. Mean Se concentrations were found as follows (in microgram/kg): 166-169
      in wheat flour, 62.5 in rye flour, 351 in white bread, 271 in rye bread, 165 in
      beef, 129 in pork, 324 in local fish, and 932 in dry milk. Se levels were high in
      some sea products and local mushrooms as well.

PMID- 7828940
TI  - [Carbon oxides in the air of school No.72 of Krasnoiarsk].

PMID- 7828941
TI  - [Parent's occupation as an important factor effecting health status of children
      (review)].
AB  - Review of literature demonstrated that adverse occupational exposures of the
      parents caused prezygotic and transplacental changes in both parents and their
      children. Embryotoxic and teratogenic effects in children of workers engaged in
      some types of production are described. Analysis of the contribution of parental
      profession to risk of oncologic diseases in children represents a new trend of
      studies. Hypotheses on teratogenic and carcinogenic mechanisms of the said
      changes are offered.

PMID- 7828942
TI  - [Biofeedback in the prevention of posture disorders in schoolchildren].

PMID- 7828943
TI  - [Health status and reproductive functions in young women -- students of
      vocational schools].

PMID- 7828944
TI  - [Study on cytogenetic activity of phenylxylylethane ,
      monochlorophenylxylylethane, samarium chloride and rubidium chloride].

PMID- 7828945
TI  - [Ecology and morbidity of population of Zaporozhie+].

PMID- 7828946
TI  - [Hygienic aspects of use of natural zeolites in national economy (review)].

PMID- 7828947
TI  - [Ecologic and epidemiologic analysis of allergies in children in Orenburg].
AB  - Results of study of relationship between the incidence of allergic diseases in
      children and the level of atmospheric air pollution in Orenburg are presented.
      Data of research in 1988-1993 has shown a trend to increase of atmospheric
      pollution by NO2, H2S, and formaldehyde. Allergic morbidity was 121.38 per 1000
      children.

PMID- 7828948
TI  - [Intermittent effect of asbestos dust and pleural cancerogenesis in rats].

PMID- 7828949
TI  - [Potential mutagenic activity of water, air and soil samples in the Sosnovyi Bor
      region].

PMID- 7828950
TI  - [Biotransformation of paracetamol in chronic experiment].

PMID- 7828951
TI  - [Ecologic and hygienic problems of elimination of chemical weapon (review)].

PMID- 7828952
TI  - [Mental work capacity in students of pedagogic college].

PMID- 7828953
TI  - [Correlation of allergies in population with environmental pollution with heavy
      metals (as exemplified by hexavalent chromium)].

PMID- 7828954
TI  - [Improvement of organization of mobile medical units on railway transport].

PMID- 7828955
TI  - [Comparative evaluation of level of hygienic knowledges in students of two
      colleges].

PMID- 7828956
TI  - [Healthy life style in students].

PMID- 7828957
TI  - [Evaluation of the level of cancerogenic waste in energetics and calculation of
      its effect on air pollution].
AB  - Investigations showed that heat plants pollute atmospheric air in towns of
      Khabarovsk district. Concentrations of benzo(a)pyrene in air of Khabarovsk,
      Komsomolsk-on-Amur, and Amursk are 4-14 times higher than its maximum allowable
      concentration.

PMID- 7828958
TI  - [Approaches to mathematical modeling of ecology-caused pathology of upper
      respiratory tract in system "organism -- population"].

PMID- 7828959
TI  - [Approaches to individual hygienic standardization of environmental parameters
      with computerized test].

PMID- 7828960
TI  - [Effect of air pollution on respiration in children].
AB  - Study of the respiratory system in children living in the town of Cheboksary
      showed the highest incidence of diseases of the respiratory tract in children
      living in the districts with the highest levels of atmospheric air pollution.

PMID- 7828961
TI  - [Blood content of tetrachloroethylene in workers of dry cleaners].
AB  - Concentrations of tetrachloroethylene (TCE) in the blood of workers employed in
      dry-cleaning workshops were measured by gas chromatography method and found to
      vary from 0,19 to 3,95 mmol/l.

PMID- 7828962
TI  - Cancer in Crohn's disease: dispelling the myths.

PMID- 7828964
TI  - Echinococcus of the liver.

PMID- 7828965
TI  - Oesophageal motility and gastro-oesophageal reflux before and after healing of
      reflux oesophagitis. A study using 24 hour ambulatory pH and pressure monitoring.
AB  - In this study 24 hour oesophageal pH and pressure monitoring was used to assess
      oesophageal motility and acid clearance in 27 patients with reflux oesophagitis
      (Savary-Miller grades I-IV), before and after healing of oesophagitis. After the
      first 24 hour study patients were treated with omeprazole 40 mg for 8-24 weeks.
      After endoscopically verified healing and withdrawing omeprazole for four days 24
      hour monitoring was repeated. A total of 106,630 pressure events was analysed. No
      significant differences were found for any of the motility variables, especially
      the number and the type of contractions, the peristaltic amplitude, duration, and
      propagation velocity did not show any changes. Separate analysis of motility
      variables before and after healing in the low and high grade oesophagitis groups
      yielded similar results. Oesophageal motor response to reflux was investigated by
      analysis of all contractions occurring in the two minute period after the onset
      of each reflux episode. Both motor response and oesophageal acid exposure (% time
      pH < 4, number of reflux episodes) did not change after healing of oesophagitis,
      thus implying that acid clearance remained unchanged. These results indicate that
      impaired motility in reflux oesophagitis is either an irreversible consequence of
      oesophageal inflammation, or a (pre-existent) factor in its pathogenesis.

PMID- 7828963
TI  - Cell biology of liver endothelial and Kupffer cells.

PMID- 7828966
TI  - Secondary oesophageal peristalsis in patients with non-obstructive dysphagia.
AB  - Secondary peristalsis was investigated in 30 patients with non-obstructive
      dysphagia and 20 age matched controls. Oesophageal motility was recorded at 3 cm
      intervals along the oesophageal body. Primary peristalsis was tested with 5 ml
      water swallows. Secondary peristalsis was stimulated with 10 ml boluses of air
      and water injected in the mid-oesophagus and by distensions (5 seconds duration)
      with a 3 cm balloon at the same level. Primary peristalsis was normal in 19 of
      the 20 control subjects and in nine of the 30 patients with dysphagia; 11
      patients had diffuse spasm and 10 had non-specific abnormalities of primary
      peristalsis. Secondary peristalsis was triggered significantly less frequently by
      air and water distension in dysphagia patients (median success rate of 10% for
      the air boluses and 0% for the water boluses) than in control subjects (50% and
      30% respectively, p < 0.005), and was abnormal in six of nine patients with
      normal primary peristalsis, nine of 11 patients with diffuse spasm and eight of
      10 patients with non-specific motor abnormalities. The median frequency of
      balloon induced secondary peristalsis, however, was not significantly different
      in the two groups (0% controls, 40% non-obstructive dysphagia, p = 0.22). For
      each stimulus, there were no significant differences in the response rate in the
      three subgroups of patients. The major pattern of failure of secondary
      peristalsis in response to the air and water boluses was the complete absence of
      any oesophageal response. The amplitude of complete secondary peristalsis
      triggered by the water boluses and the balloon was greater in the patients with
      dysphagia (p = 0.03) than in normal subjects, while the amplitude of the
      secondary peristaltic responses triggered by the air boluses was similar in the
      two groups. Secondary peristaltic velocity was also similar in normal subjects
      and patients with non-obstructive dysphagia. Patients with non-obstructive
      dysphagia show a noticeable defect in the triggering of secondary peristalsis
      which may make an important contribution to the delayed oesophageal bolus transit
      and dysphagia seen in this condition.

PMID- 7828967
TI  - Prospective evaluation of 24 hour ambulatory pH metry in Belsey Mark IV
      antireflux surgery.
AB  - This study evaluated the effect of the 270 degrees Belsey Mark IV fundoplication
      on 24 hour ambulatory pH metry variables. Thirty seven patients with confirmed
      gastro-oesophageal reflux disease who had a Belsey Mark IV antireflux procedure
      were evaluated preoperatively and three to six months postoperatively including
      endoscopy, lower oesophageal sphincter manometry, and 24 hour ambulatory pH
      metry. In 30 of 37 patients the Belsey Mark IV fundoplication was judged
      successful based on symptom relief and healing of oesophagitis. In these 30
      patients percentage reflux for total, upright, and supine time (median and range)
      decreased significantly (p < 0.001) from 10.0% (2.7-35.3%), 10.8% (3.2-39.9%),
      and 6.7 (0.0-33.0%) respectively to 0.5% (0.0-7.4%), 0.6% (0.0-13.7%), and 0.1%
      (0.0-4.9%) after operation. This decrease in reflux time resulted predominantly
      from a significant (p < 0.001) reduction in the number of reflux episodes from 98
      (23-231) to 14 (0-82) postoperatively. Normalisation of total reflux time (upper
      limit of normal for time with pH below 4:4%) was found in 89% and normalisation
      of total and upright and supine reflux in 64% of successfully operated patients
      with confirmed abnormal acid reflux before operation. A successful antireflux
      procedure was associated with significant (p < 0.001) increases in lower
      oesophageal sphincter pressure from 7.8 (0.6) mm Hg to 14.5 (0.7) mm Hg mean
      (SEM). In seven patients with a failed antireflux operation basal lower
      oesophageal sphincter pressure did not change significant;y (preoperative value
      5.7 (1.3) mm Hg; postoperative value 7.8 (0.8) mm Hg). In these patients reflux
      time did not decrease after the operation and remained in the abnormal range in
      all patients. It is concluded that a successful, in contrast with a failed,
      Belsey Mark IV fundoplication is associated with significant decreases in total,
      upright, and supine reflux time. Normalisation of pH metry variables is not a
      prerequisite for successful antireflux surgery. A surgery. A successful 270
      degree Belsey Mark IV fundoplication was associated with a significant increase
      in basal lower oesophageal sphincter pressure, in contrast with the failure
      group. Restoration of a sufficient lower oesophageal sphincter barrier is an
      important aim in antireflux surgery.

PMID- 7828968
TI  - Primary peristalsis is the major acid clearance mechanism in reflux patients.
AB  - This study examined the clearance of gastric acid from the oesophagus in ambulant
      patients with gastro-oesophageal reflux. Eighteen patients with proved reflux
      disease were studied, nine with (group 1) and nine without (group 2) endoscopic
      oesophagitis. Oesophageal pressure and pH were recorded over 24 hours. Pressures
      were measured by a probe with five sensors: a 5 cm long sensor in the lower
      oesophageal sphincter, three sensors in the body of the oesophagus, and one at
      the pharynx to detect swallowing. Oesophageal pH was monitored 5 cm above the
      lower oesophageal sphincter. Manometric activities were classified as either
      peristaltic or ineffective. The latter included simultaneous, non-transmitted,
      and low amplitude peristaltic contractions. A reflux episode was defined as
      starting when pH fell to less than 4 and ending when the pH rose to 5. When the
      rise to pH 5 took place in three or more discrete steps after motor responses to
      gastro-oesophageal reflux, the pH steps were labelled as initial change (I),
      middle changes (M), and last change (L). A total of 595 episodes of gastro
      oesophageal reflux and 1626 associated motor events were analysed. Of these, 1331
      (81.9%) were classed as primary peristaltic activity, 174 (10.7%) as primary
      ineffective activity, 46 (2.8%) as secondary peristaltic activity, and 75 (4.6%)
      as secondary ineffective activity. There were no significant differences in
      initial change (p > 0.05), middle changes (p > 0.05), and last change (p > 0.05)
      between group 1 and group 2. In all patients, the successive changes of pH in
      response to motor activity were significantly different (p = 0.0001) between
      initial, middle, and last changes. Last change was significantly higher when
      compared with initial (p=0.001) and middle changes (p<0.001). Primary oesophageal
      peristalsis was the most frequent motor response to gastro-oesophageal reflux.
      The last motor activity during reflux showed the greatest change in pH.

PMID- 7828969
TI  - Intragastric nitric oxide production in humans: measurements in expelled air.
AB  - High values (800-6000 parts per billion) of nitric oxide (NO) in expelled air
      from the stomach were shown in humans by chemiluminescence technique. These NO
      values were more than 100 times higher than those found in orally exhaled air.
      Intragastric NO production is probably non-enzymatic, requiring an acidic
      environment, as NO in expelled air was reduced by 95% after pretreatment with the
      proton pump inhibitor omeprazole. Furthermore, large amounts of NO were formed in
      vitro from lettuce and saliva when placed in hydrogen chloride (pH < 2). In
      conclusion, large amounts of NO are formed intragastrically in humans and this
      source of NO may be of importance for the integrity of the gastric mucosa in
      health and disease. Measurements of NO in expelled air might be of value as a non
      invasive method for estimation of gastric acidity.

PMID- 7828970
TI  - Evaluation of the trophic effect of longterm treatment with the histamine H2
      receptor antagonist loxtidine on rat oxyntic mucosa by differential counting of
      dispersed cells.
AB  - To evaluate whether the general trophic effect of gastrin on the oxyntic mucosa
      is an indirect effect mediated by histamine H2 receptors, sustained 24 hour
      hypergastrinaemia was induced in Sprague-Dawley rats by treatment with the long
      acting and potent histamine H2 antagonist loxtidine for five months. The trophic
      effect was assessed by weight, enumeration of total mucosal cells, parietal
      cells, and enterochromaffin like cells in smears stained for the actual cells
      after enzymatic dispersion of the mucosa, and by biochemical analysis of oxyntic
      mucosal homogenates. The weight of the whole stomach and the oxyntic mucosa
      increased by 12.7% (p = 0.016) and 27.5% (p = 0.006), respectively. Total oxyntic
      mucosal protein content increased by 28.7% (p = 0.058). Total numbers of mucosal
      cells and parietal cells increased by 11.9% (NS) and 24.1% (NS), respectively.
      The amount of the parietal cell specific enzyme H+,K(+)-ATPase was unchanged. On
      the other hand, the number of enterochromaffin like cells and related parameters,
      histidine decarboxylase activity and histamine content of the oxyntic mucosa,
      showed a pronounced and significant increase. It is concluded that the general
      trophic effect of gastrin on the oxyntic mucosa is not mediated by the histamine
      H2 receptor. The tropic effect of gastrin on the parietal cell seems, in contrast
      with that on the enterochromaffin like cell, not to be specific but only
      reflecting the general trophic effect on the oxyntic mucosa.

PMID- 7828971
TI  - Percutaneous endoscopic gastrostomy in a general hospital: prospective evaluation
      of indications, outcome, and randomised comparison of two tube designs.
AB  - The indications for percutaneous endoscopic gastrostomy (PEG) and patient
      outcome, were examined prospectively in the setting of a general hospital. In the
      course of 26 months, 76 patients underwent PEG (median age 62 years (range 18
      99)) and were followed up for 6887 patient days. The median (range) duration of
      PEG feeding was 93 (3-785) days. The procedure was carried out for neurological
      indications in 76% of cases (stroke 51%) and 53% of patients were severely
      malnourished (body mass index < 17 kg/m2) at the time of referral. In 12 (16%)
      patients swallowing recovered and the PEG was removed after a median (range) of
      55 days (20-150). Three (4%) deaths were related to PEG (one oesophageal
      perforation, one haemorrhage, and one aspiration pneumonia). One patient
      developed peritonism and ileus, which resolved with conservative treatment. Minor
      complications included local sepsis 3%, tube blockage 12%, and tube connector
      leak 5%. During seven days of observation, demands on nursing time for routine
      care of the PEG were the same as for nasogastric tube feeding, median (range) 21
      (4-42) v 16 (4-40) min/day respectively, but in about half the latter cases the
      tube had to be replaced at least once. Over 15 months, 29 patients were
      randomised to receive a 1.9 mm inner, 2.9 mm (9F) outer diameter Fresenius and 27
      a 3.0 mm inner, 4.0 mm (12F) outer diameter Bower polyurethane tube and were
      followed for 2920 and 2388 patient days respectively. There was no difference in
      the insertion time (median (range) 20 (10-45) v 24 (10-45) min respectively) or
      number of patients with complications (three v eight patients NS), although there
      were more minor mechanical problems (three v 12, p < 0.01) with the 12F tube. The
      internal anchoring device of the 12F tube allowed its non-endoscopic removal, a
      method applicable too 16% of cases. No tubes were removed because of blockage.

PMID- 7828972
TI  - Inhibitory effect of polyunsaturated fatty acids on the growth of Helicobacter
      pylori: a possible explanation of the effect of diet on peptic ulceration.
AB  - Diets high in polyunsaturated fatty acids may protect against duodenal ulcer,
      possibly through inhibiting the growth of Helicobacter pylori. This hypothesis
      was tested in vitro by incubating H pylori microaerophilically with a range of
      polyunsaturated fatty acids. omega-3 Linolenic acid significantly, but
      reversibly, inhibited growth at 1.8, 2.5, and 5 x 10(-4) M (p < 0.01), while
      concentrations of 10(-3) M killed virtually all organisms, with cell lysis
      observed by electron microscopy. Similar inhibitory effects were seen with other
      polyunsaturated fatty acids, at concentrations of 2.5 x 10(-4) M the relative
      inhibitory potencies were oleic (C18:1) < linoleic (C18:2) < arachidonic (C20:4)
      < omega-3 linolenic (C18:3) = omega-6 linolenic (C18:3) = eicosapentanoic (C20:5)
      acid. Cell fractionation studies with 14C labelled linolenic acid showed that the
      linolenic acid was associated with the membrane fraction. Commonly ingested
      dietary polyunsaturated fatty acids inhibit the growth of H pylori in vitro, an
      effect which deserves further in vivo study.

PMID- 7828973
TI  - High prevalence of Helicobacter pylori metronidazole resistance in migrants to
      east London: relation with previous nitroimidazole exposure and gastroduodenal
      disease.
AB  - A high prevalence of metronidazole resistance in Helicobacter pylori is reported
      in developing countries. This study examined whether migrants referred for
      diagnostic gastroscopy at a United Kingdom centre (n = 54), had a higher
      prevalence of metronidazole resistance than subjects born in the United Kingdom
      attending endoscopy (n = 46). Records of nitroimidazole treatment prescribed in
      the United Kingdom was obtained in 83 patients to find out if there was an
      association between H pylori metronidazole resistance and previous ingestion of
      either metronidazole or tinidazole. The prevalence of metronidazole resistant
      isolates varied according to country of birth: Bangladesh (90%, 27 of 30), other
      countries (67%, 16 of 24), and United Kingdom (37%, 17 of 46) (p < 0.001). Among
      those born in the United Kingdom, women were more likely to harbour resistant H
      pylori than men (54% v 18% respectively, p = 0.01) and more likely to have a
      history of previous nitroimidazole ingestion (41% v 11% respectively, p = 0.02).
      Patients previously exposed to either metronidazole or tinidazole were more
      likely to harbour resistant strains (84% (27 of 32) v 41% (21 or 51), p <
      0.0001). The distribution of gastroduodenal disease, assessed endoscopically, was
      not affected by metronidazole resistance status.

PMID- 7828974
TI  - Cytokine gene expression in Helicobacter pylori associated antral gastritis.
AB  - Infection of the gastric antrum by Helicobacter pylori is characterised by a
      cellular inflammatory infiltrate. Whether cytokines are involved in the
      pathogenesis of this gastritis has been investigated by studying the effect of
      eradicating H pylori on the expression of genes encoding the cytokines
      interleukin 8 (IL-8) and tumour necrosis factor alpha (TNF-alpha) in the antral
      mucosa. Gastric antral biopsy specimens were taken from nine patients with
      duodenal ulcers and cytokine transcripts were identified and quantified by
      northern blotting. After H pylori had been eradicated the chronic inflammatory
      infiltrate decreased in all the patients and the polymorphonuclear infiltrate
      virtually disappeared. Expression of genes also decreased. After eradication, the
      median TNF-alpha mRNA/rRNA fell to 48% (p = 0.02) and the median IL-8 mRNA/rRNA
      fell to 5% (p = 0.004) of initial values. These results support the role of
      increased synthesis of these cytokines in the pathogenesis of the gastritis.

PMID- 7828975
TI  - Improved fold width and increased acid secretion after eradication of the
      organism in Helicobacter pylori associated enlarged fold gastritis.
AB  - This study examined the effects of eradication of Helicobacter pylori (H pylori)
      infection on gastric mucosal morphology and acid secretion. Sixteen H pylori
      positive patients with enlarged gastric body folds were divided into two groups:
      (a) patients with moderate enlargement (fold width: 6 to 10 mm, n = 8) and (b)
      patients with severe enlargement (> 10 mm, n = 8). After successful treatment,
      gastric body fold width was reduced in both groups (p < 0.01) with an associated
      decrease in inflammatory infiltrates in the body mucosa (p < 0.01 and p < 0.05).
      Basal acid output and tetragastrin stimulated maximal acid output (mean (SEM)) in
      all 16 patients significantly increased from 1.1 (0.5) to 2.9 (0.9) mmol/h (p <
      0.05) and from 5.4 (1.3) to 18.7 (2.3) mmol/h (p < 0.01), respectively, with a
      significant decrease in fasting serum gastrin concentrations, from 127.1 (16.1)
      to 59.6 (3.8) pg/ml (p < 0.01). The increase in acid secretion after eradication
      of H pylori was more noticeable in the severe group, who had shown lower acid
      secretion and higher serum gastrin concentrations (p < 0.05) before eradication,
      than the increase seen in the moderate group. The decreases in ammonia nitrogen
      content seen after eradication were significant in basal (from 0.91 (0.17) to
      0.37 (0.08) mmol/h, p < 0.05) and stimulated gastric secretions (from 1.57 (0.19)
      to 0.37 (0.13) mmol/h, p < 0.01), although these changes were too small to
      explain the increases in basal acid output and maximal acid output. These results
      suggest that inflammation of the gastric body mucosa caused by H pylori infection
      is associated with enlarged gastric body folds and inhibition of acid secretion
      in H pylori positive patients with enlarged gastric body folds.

PMID- 7828976
TI  - Characterisation of oxidative injury to an intestinal cell line (HT-29) by
      hydrogen peroxide.
AB  - Reactive oxygen metabolites have been implicated in causing epithelial cell
      injury in colonic inflammation. A model of oxidant injury in intestinal
      epithelial cells has been developed in which HT-29-18-C1 cells are injured with
      graded concentrations of hydrogen peroxide and characterised by the MTT test. The
      MTT test was validated as a cytotoxicity assay and has a similar sensitivity to
      hydrogen peroxide induced injury as the assay of intracellular adenosine
      triphosphate. Exposure to a range of hydrogen peroxide concentrations (0.05-20
      mM) for varying duration (5-120 min) showed that injury was dependent on time and
      concentration. The median lethal dose (LD50) for one hour exposure to hydrogen
      peroxide was approximately 0.1 mM. Injury from hydrogen peroxide was only
      partially reversible as determined by the MTT test and assay of cellular
      proliferation by crystal violet staining. There was an exponential loss of
      hydrogen peroxide when incubated with HT-29-18-C1 cells (t1/2 35 min).
      Experiments with 0.5 mg/ml aminotriazole and 0.5-2 mM buthionine sulphoximine
      suggested hydrogen peroxide breakdown was predominantly caused by catalase rather
      than glutathione peroxidase. Injury resulting from 1 mM hydrogen peroxide could
      be reduced by either coincubation of cells with 1,10-phenanthroline, an Fe2+
      chelator, or preincubation with deferoxamine, and Fe3+ chelator, suggesting the
      participation of Fe2+ and Fe3+ in hydrogen peroxide induced injury. In
      conclusion, hydrogen peroxide induces injury in HT-29-18-C1 cells both directly
      and by generation of the hydroxyl radical.

PMID- 7828977
TI  - Lymphoid and non-lymphoid cells in the epithelium and lamina propria of
      intestinal mucosa of pigs.
AB  - The jejunum and ileum of 5 day old and adult normal pigs and of 45 day old germ
      free pigs were used to study the lymphocyte pools in the epithelium and lamina
      propria by sequential treatments with EDTA, four hours, and 12 hours of
      collagenase treatment. In adult animals the incubation of the jejunal wall with
      EDTA resulted in mean (SD) 26.8 (10.9) x 10(6) intraepithelial lymphocytes per g
      of tissue. The ileal wall gave lower cell yields. After complete digestion of the
      lamina propria by collagenase a further yield of 35.2 (10.2) x 10(6)/g
      lymphocytes was achieved. The separation of the gut wall from 5 day old pigs
      resulted in a 10-fold lower total lymphocyte yield, and the tissue was totally
      digested after four hours of collagenase treatment. Many eosinophils and mast
      cells were found in the suspensions from adult animal tissues after the
      collagenase treatment; 4.7 x 10(6)/g and 4.8 x 10(6)/g, respectively. The
      suspensions after 12 hour collagenase incubation contained up to 30% plasma
      cells. Almost all cells isolated by EDTA incubation were CD8+ T cells. After
      collagenase incubation CD4+ and CD8+ T lymphocytes were found in all animal
      groups, and in adult animals up to 20% surface Ig+ cells were harvested. When the
      incorporation of the thymidine analogue bromodesoxyuridine was used to study the
      lymphocyte production in vivo 3 to 7% lymphocytes in the epithelium were labelled
      24 hours later (lamina propria T lymphocytes about 1%). In this study lymphoid as
      well as non-lymphoid cells have been analysed in mucosal cell suspensions. The
      absolute cell yield per gram of mucosal tissue is a basis to estimate the pool
      sizes of intraepithelial and lamina propria lymphocytes.

PMID- 7828978
TI  - Ulcerative colitis and Crohn's disease: a comparison of the colorectal cancer
      risk in extensive colitis.
AB  - The risk of developing colorectal cancer has been compared in two identically
      selected cohorts of patients with extensive Crohn's colitis (n = 125) and
      extensive ulcerative colitis (n = 486). In both groups the effects of selection
      bias have been reduced wherever possible. There was an 18-fold increase in the
      risk of developing colorectal cancer in extensive Crohn's colitis and a 19-fold
      increase in risk in extensive ulcerative colitis when compared with the general
      population, matched for age, sex, and years at risk. The absolute cumulative
      frequency of risk for developing colorectal cancer in extensive colitis was 8% at
      22 years from onset of symptoms in the Crohn's disease group and 7% at 20 years
      from onset in the ulcerative colitis group. The relative risk of colorectal
      cancer was increased in both ulcerative colitis and Crohn's disease among those
      patients whose colitis started before the age of 25 years. Whether the absolute
      risk is greater in the younger age group or merely reflects that the expected
      number of carcinomas increases with age is uncertain. While there is an increased
      risk of developing colorectal cancer in extensive colitis the number of patients
      with Crohn's disease who actually develop colorectal cancer is small because many
      patients with extensive Crohn's colitis undergo colectomy early in the course of
      their disease to relieve persistent symptoms unresponsive to medical treatment.

PMID- 7828979
TI  - Increased group II phospholipase A2 in colonic mucosa of patients with Crohn's
      disease and ulcerative colitis.
AB  - The immunochemical protein content of group II phospholipase A2 (PLA2) and PLA2
      enzymatic activity were measured for colonic mucosal biopsy samples obtained from
      patients with either Crohn's disease of the colon or ulcerative colitis, and
      control patients without inflammatory bowel disease. Immunoreactive group II PLA2
      (IR-PLA2 II) content and PLA2 activity in actively inflamed colonic mucosa of
      Crohn's disease patients were significantly higher than those in inactively
      inflamed mucosa of Crohn's disease patients and the colonic mucosa of controls.
      IR-PLA2 II content and PLA2 activity in severely inflamed mucosa of ulcerative
      colitis patients were significantly higher than those in the colonic mucosa of
      the controls. Mucosal PLA2 enzymatic activity was closely correlated with mucosal
      IR-PLA2 II content in patients with Crohn's disease and ulcerative colitis. These
      results suggest that an increase in PLA2 enzymatic activity in inflamed colonic
      mucosa of Crohn's disease and ulcerative colitis was mainly attributed to
      increased protein content of group II PLA2, and that an increase in mucosal group
      II PLA2 may be involved in the pathogenesis of intestinal inflammation of Crohn's
      disease and ulcerative colitis.

PMID- 7828980
TI  - Microalbuminuria in inflammatory bowel disease.
AB  - Microalbuminuria independently predicts the development of nephropathy and
      increased cardiovascular morbidity and mortality in diabetic patients, but it may
      be an indicator of the acute phase response. This study examined microalbuminuria
      as a marker of the acute phase response in patients with inflammatory bowel
      disease and correlated it with the disease activity in 95 patients with
      inflammatory bowel disease (ulcerative colitis (n = 52), Crohn's disease (n =
      43)) determined by the simple index of Harvey and Bradshaw. Fifty patients were
      in complete clinical remission and 45 patients had active disease.
      Microalbuminuria was detected in all patients with inflammatory bowel disease
      (147 (17) v 18 (2) microgram/min, inflammatory bowel disease v controls mean
      (SEM), p < 0.007). Patients with active inflammatory bowel disease had higher
      concentrations of microalbuminuria compared with patients in remission (206 (19)
      v 65 (8) microgram/min, mean (SEM), p < 0.0001). Eight patients with active
      inflammatory bowel disease who were sequentially followed up with measurements of
      microalbuminuria had significantly lower values, when the disease was inactive
      (active inflammatory bowel disease 192 (44) v inactive inflammatory bowel disease
      64 (14) microgram/min, p < 0.03). There was a significant correlation with the
      simple index of Harvey and Bradshaw (r = 0.818, p < 0.0001). Microalbuminuria
      values were significantly lower in inflammatory bowel disease patients in
      remission, maintained with olsalazine compared with those patients maintained
      with mesalazine and salazopyrine, but no significant difference was seen in
      values of microalbuminuria in active inflammatory bowel disease patients
      receiving different salicylates. This study also measured serum amyloid-A as an
      indicator of the acute phase response in the same patients. Serum amyloid-A was
      significantly increased in active disease compared with inactive disease (151
      (43) v 33 (7) or controls 11 (2) micrograms/ml, p < 0.05). In conclusion
      microalbuminuria is present in abnormal amounts in all patients with active
      inflammatory bowel disease, and values fall when the disease is quiescent.
      Microalbuminuria is probably a consequence of an acute phase response and
      provides a simple, rapid, and inexpensive test, which has the potential to
      monitor inflammatory bowel disease activity and response to treatment.

PMID- 7828981
TI  - Nerve growth factor receptor immunostaining suggests an extrinsic origin for
      hypertrophic nerves in Hirschsprung's disease.
AB  - The expression of nerve growth factor receptor in colon from 20 patients with
      Hirshsprung's disease and 10 controls was studied immunohistochemically. The
      myenteric and submucous plexuses in the ganglionic bowel and hypertrophic nerve
      trunks in the aganglionic bowel displayed strong expression of nerve growth
      factor receptor. The most important finding was the identical localisation of
      nerve growth factor receptor immunoreactivity on the perineurium of both
      hypertrophic nerve trunks in Hirshsprung's diseases, and of normal extrinsic
      nerves, seen as a thick ring surrounding the nerve trunks. This suggests that the
      hypertrophic nerve trunks are of extrinsic origin and that nerve growth factor
      receptor plays a role in their development and maintenance.

PMID- 7828982
TI  - Clinical significance of Clostridium difficile and its toxins in faeces of
      immunocompromised children.
AB  - In this study, clinical and laboratory findings were tested for correlation with
      the presence of Clostridium difficile. The toxigenicity of the isolated strains
      and the toxins were determined in faecal samples of immunocompromised children
      admitted to a single room for protective isolation. Using the toxin assay as the
      gold standard, the culture sensitivity of toxigenic C difficile was 94.1%, the
      specificity 93.8%, the positive predictive value 62.8%, and the negative
      predictive value 99.3%. Correction for stools with a positive culture of
      toxigenic C difficile preceding detection of toxin, resulted in a positive
      prediction value of 78.4%. A statistically significant association was found
      between a positive faecal toxin assay and fever, and between a positive culture
      of toxigenic C difficile and abdominal pain: 42% of the patients with positive
      toxin assays had fever versus 21% with negative toxin assays, and 66% of the
      patients with a positive culture for toxigenic C difficile had abdominal pain,
      versus 22% with negative cultures. Further analysis of the cultures and toxin
      assays showed no statistically significant association with diarrhoea, fever,
      white blood cell count, C reactive protein concentrations, or abdominal pain.
      Based on these findings, it is suggested that immunocompromised children should
      be treated when toxigenic C difficile is cultured or when toxin is detected in
      stool samples.

PMID- 7828983
TI  - Effect of Escherichia coli enterotoxins on macromolecular absorption.
AB  - Macromolecular absorption of gliadin, a wheat protein and alpha lactalbumin, a
      milk protein was evaluated in control and Escherichia coli enterotoxin (heat
      stable, heat-labile, and both heat-stable and heat-labile enterotoxin) treated
      mice. The peak concentration of gliadin and lactalbumin was two hours and three
      hours after their ingestion, respectively. There was also a significant increase
      (p < 0.01) in the absorption of both the proteins in all the three toxin treated
      groups compared with the control group. These results suggest that intestinal
      permeability and macromolecular absorption changes after E coli infection.

PMID- 7828984
TI  - Diagnostic yield and management benefit of laparoscopy: a prospective audit.
AB  - A prospective audit of the diagnostic yield and management benefit of laparoscopy
      was undertaken in 220 consecutive patients. The procedure was performed
      electively in 180 patients and as an emergency in 40. The indications for
      laparoscopy in the elective group were suspected hepatic disease, staging of
      intra-abdominal malignancy, diagnostic problems, and chronic abdominal pain.
      Emergency laparoscopy was performed in patients admitted with acute abdominal
      pain. Diagnostic benefit varied with the indication for the procedure: liver
      disease 71%, tumour staging 87%, uncertain diagnosis 74%, acute abdominal pain
      100%, and chronic abdominal pain 41%. Clinical management was significantly
      influenced by laparoscopy in 15 of 21 (71%) patients with liver disease, 10 of 30
      (33%) with intra-abdominal malignancy, 5 of 19 (26%) with uncertain diagnosis, 32
      of 40 (80%) with acute abdominal pain, and 15 of 110 (23%) patients with chronic
      abdominal pain. A wrong assessment of the nature or stage of the disease was made
      by laparoscopy in 3 of 220 (1.0%). There was no morbidity or mortality attributed
      to laparoscopy in the study.

PMID- 7828985
TI  - Phenotypic expression in familial adenomatous polyposis: partial prediction by
      mutation analysis.
AB  - The phenotypic expression in familial adenomatous polyposis (FAP) is variable.
      This study compares the phenotype of 27 patients with an identical 5 base pair
      (bp) deletion at codon 1309 with a group of 61 matched patients with FAP where
      knowledge of specific mutations is not available and with seven other different
      mutations in 24 subjects. Patients with the codon 1309 deletion have
      significantly more colorectal polyps at the time of colectomy than age and sex
      matched FAP controls (p = 0.0001). The median number of polyps in colectomy
      specimens of patients with the deletion at codon 1309 was 4000 (interquartile
      (IQ) range 3000-4875), compared with 600 (IQ range 488-1400) in the matched
      controls. Mutations at codon 1323, 1407, and 233 were also associated with large
      numbers of polyps. Desmoid disease and extracolonic cancers were more common with
      the mutation at codon 1309 (p = 0.003). In conclusion, there may be a correlation
      between a specific germline mutation and the number of large bowel polyps. There
      is residual heterogeneity in phenotypic expression, however, and this may result
      from the influence of other genes, specific environmental factors or chance.

PMID- 7828986
TI  - Rectal mucosal ornithine decarboxylase activity in familial adenomatous polyposis
      after ileorectal anastomosis.
AB  - Resection of the colon in patients with familial adenomatous polyposis frequently
      results in the regression of polyps in the remaining rectum, suggesting a
      reduction of cellular proliferation. These patients remain at risk of developing
      rectal cancer but whether this risk increases with time is uncertain. Since
      ornithine decarboxylase activity is associated with cellular proliferation,
      mucosal ornithine decarboxylase was measured in rectal biopsy specimens from
      patients with familial adenomatous polyposis after ileorectal anastomosis (n =
      36) and from normal controls (n = 30). The relationship between ornithine
      decarboxylase activity, age, and time from surgery was also examined. Median
      ornithine decarboxylase activity in familial adenomatous polyposis patients after
      ileorectal anastomosis (186, interquartile range (IQR) 107-534 pmol/mg protein/h)
      was not different from that in control subjects (227, IQR 123-374, p = 0.6). When
      patients were divided into three equal groups according to age, however, younger
      patients (< 25 years) had significantly higher activity than both older age
      groups (p < 0.02). Similarly, when patients were stratified according to the time
      elapsed since surgery, those who had had surgery less than six years previously
      had a significantly higher ornithine decarboxylase activity than those in whom a
      longer time interval had elapsed since surgery (p = 0.02). These results indicate
      that after colon resection, ornithine decarboxylase activity in patients with
      familial adenomatous polyposis is similar to that in normal controls but seems to
      fall over time. This may explain the regression of rectal polyps after colonic
      resection in this disorder.

PMID- 7828987
TI  - Mutations of Ki-ras and p53 genes in colorectal cancer and their prognostic
      significance.
AB  - The series of genetic changes leading to malignancy in colorectal cancer is well
      reported. This includes mutational activation of the proto-oncogene Ki-ras and
      mutation/deletion of the p53 tumour suppressor gene. The frequency of these
      mutations was investigated in a panel of 52 colorectal cancer patients using a
      combination of immunocytochemistry and non-radioactive, digoxigenin-labelled in
      situ hybridisation. Sixty two per cent (32 of 52) of the study population were
      positive for p53 overexpression and 36% (19 of 52) positive for Ki-ras mutation.
      Twenty seven per cent (14 of 52) of the patients expressed both mutations.
      Mutation of either the p53 or the Ki-ras gene did not correlate with Dukes's
      stage, tumour differentiation or 5 year survival rate of the patients. Most of
      the rectal carcinoma specimens (11 of 15) showed p53 over-expression but the
      significance of this was not supported statistically. Thus detection of molecular
      changes is becoming more amenable to incorporation into routine histological
      carcinoma assessment because of the advent of non-radioactive labelling in in
      situ hybridisation and antibodies suitable for paraffin wax embedded specimens.
      The significance of these mutations in disease prognosis, however, remains
      questionable.

PMID- 7828988
TI  - Cimetidine inhibits in vivo growth of human colon cancer and reverses histamine
      stimulated in vitro and in vivo growth.
AB  - The effect of histamine and cimetidine on the growth of four human colon cancer
      cell lines was studied. Histamine significantly stimulated the uptake of
      tritiated thymidine in vitro in a dose dependent manner, to a maximum of 120% and
      116% of controls for C170 and LIM2412, respectively. This effect was antagonised
      by cimetidine, but not diphenhydramine. Histamine also stimulated a dose
      dependent increase in cyclic adenosine monophosphate accumulation in C170 cells,
      antagonised by cimetidine. When grown as subcutaneous xenografts in Balb/c nu/nu
      mice, cimetidine had a significant inhibitory effect on the same two cell lines.
      The final volume of C170 tumours in animals given cimetidine was 44% of controls.
      This response was dose dependent, plateauing at a cimetidine dose of 50
      mg/kg/day. The final volume of LIM2412 tumours in animals given cimetidine was
      60% of controls. Histamine administered locally by a mini-osmotic pump stimulated
      C170 tumour growth to 164% of controls, was antagonised by cimetidine at a dose
      of 200 mg/kg/day, but not by lower concentrations. Histamine has a trophic effect
      on at least two colorectal cancer cell lines in vivo and in vitro. As this effect
      is antagonised by cimetidine, it may be mediated via tumour histamine type 2
      receptors.

PMID- 7828989
TI  - Monitoring oxidative damage in patients with liver cirrhosis and different daily
      alcohol intake.
AB  - This study looked at the possible association between alcohol abuse and free
      radical mediated oxidative injury by examining the presence of oxidative damage,
      as monitored by erythrocyte malonildialdehyde and plasma lipid hydroperoxides, in
      patients with liver cirrhosis and different lifetime daily alcohol intake. All
      patients with an alcohol intake above 100 g/day (ALC) showed concentrations of
      malonildialdehyde and lipid hydroperoxide on average four to fivefold higher than
      cirrhotic patients with alcohol intake below 100 g/day (NAC) or healthy controls.
      Further subgrouping of ALC patients showed that those with alcohol intake ranging
      between 100 and 200 g/day (ALC1) had malonildialdehyde and lipid hydroperoxide
      concentrations significantly lower than those with an intake higher than 200
      g/day (ALC2). These differences were not related to the extent of liver injury or
      to the liver derangement as assessed by Child's classification. The increase in
      lipid peroxidation markers in ALC cirrhotic patients was associated with a
      decrease in, respectively, plasma alpha-tocopherol and erythrocyte glutathione
      concentrations. Significant differences were also seen between ALC1 and ALC2
      groups in plasma alpha-tocopherol, but not in erythrocyte glutathione
      concentrations. The concentrations of alpha-tocopherol and glutathione in the
      blood of NAC patients were in contrast not substantially different from those of
      healthy controls. The close association between oxidative damage and alcohol
      abuse suggested that free radical intermediates produced during ethanol
      metabolism might be responsible for causing oxidative damage.

PMID- 7828990
TI  - Lipid peroxidation in rats chronically fed ethanol.
AB  - Chronic alcohol consumption induces cytochrome P450IIE1, enabling habitual
      abusers to consume far greater quantities of alcohol than normal subjects. This
      pathway of metabolism leads to the production of free radical species, which
      cause tissue damage through peroxidation of cell membranes. Groups of Wistar rats
      of equal male: female ratio (n = 24) were fed alcohol by gavage twice daily to
      achieve a dosage of 15 g/kg body weight. Mean peak blood alcohol concentrations
      of 186 mg% were produced in males and 156 mg% in females. The animals were
      allowed free access to standard laboratory chow and water. Control animals were
      pair-fed to the alcoholic group and fed isocaloric glucose by gavage. Groups of
      animals were killed between 9 and 11 am on consecutive mornings, after nocturnal
      feeding, since it has previously been shown that fasting rapidly depletes hepatic
      glutathione concentrations. Hepatic glutathione was measured by a
      spectrophotometric enzymatic recycling procedure. As a marker of lipid
      peroxidation hepatic malonaldehyde (MDA) was measured by high performance liquid
      chromatography. Hepatic MDA was increased in the alcoholic group (p < 0.001), as
      was total hepatic glutathione (p < 0.0001). Plasma concentrations of alpha
      tocopherol were increased in the alcoholic group, but ascorbic acid and
      superoxide dismutase values were not affected. No sex differences were detected.
      The increased MDA production in the alcohol group is strong evidence that lipid
      peroxidation is a mechanism of alcoholic tissue damage. The rise in hepatic
      glutathione may be an adaptive response to free radical production that protects
      the rat against tissue damage.

PMID- 7828991
TI  - Bacterial translocation in cirrhotic rats. Its role in the development of
      spontaneous bacterial peritonitis.
AB  - Bacterial translocation occurs in ascitic cirrhotic rats, but its association
      with ascites infection is unknown. The aim of this study was to assess the
      relation between bacterial translocation and ascites infection in cirrhotic rats.
      Male Sprague-Dawley rats were induced to cirrhosis with intragastric CCl4.
      Ascitic fluid, portal and peripheral blood, mesenteric lymph nodes, liver and
      spleen samples were cultured before death in those cirrhotic rats with less
      (group A) or more (group B) than 250 polymorphonuclear neutrophils/mm3 in ascitic
      fluid, as well as in healthy control rats. Histological examination of jejunum,
      ileum, and caecum was also performed. Bacterial translocation occurred in 45% of
      ascitic rats (without differences between groups A and B), but in 0% controls (p
      = 0.01). Bacterial translocation was associated with positive ascitic fluid
      culture in 60% of the cases. In all of them the same bacterial species was
      isolated in both mesenteric lymph node and ascitic fluid. Submucosal caecal
      oedema (100%), ileal lymphangiectasia (41%), and caecal inflammatory infiltrate
      (41%) occurred in ascitic rats, the last being associated with ascitic fluid
      positive culture (p = 0.04). These results suggests that bacterial translocation
      occurs frequently in ascitic cirrhotic rats, and may play a permissive, but not
      unique, part in a number of ascites infections. Whether histological changes seen
      in cirrhotic ascitic rats favour bacterial translocation remains to be
      elucidated.

PMID- 7828992
TI  - Addition of dimethylsulphoxide to methyl-tert-butyl ether and ethyl propionate
      increases cholesterol dissolving capacity and cholesterol gall stone dissolution
      in vitro.
AB  - There is a discrepancy between in vitro cholesterol dissolving efficacy of methyl
      tert-butyl ether (MTBE) and ethyl propionate and cholesterol gall stone
      dissolution in vivo. This study investigated whether the presence of bile changes
      the cholesterol dissolving capacity of MTBE and ethyl propionate. The addition of
      dimethylsulphoxide to MTBE or ethyl propionate was also studied to discover if it
      improves the dissolving capacity for cholesterol gall stones. The presence of
      bile caused a 25% decrease in cholesterol dissolving capacity of both MTBE and
      ethyl propionate (p < 0.0001). This inhibitory effect of bile could be overcome
      by the addition of dimethyl-sulphoxide: dimethylsulphoxide caused an increase in
      cholesterol dissolving capacity of MTBE and ethyl propionate, the increase
      depending on the dimethyl-sulphoxide/bile ratio in the mixture. Mean dissolution
      time of weight, size, and patient matched cholesterol gall stones was 220 minutes
      in MTBE and 130 minutes in MTBE/dimethylsulphoxide (p < 0.0001). No stones
      dissolved completely in ethyl propionate or ethyl propionate/dimethyl-sulphoxide
      within 300 minutes. In conclusion, MTBE/dimethylsulphoxide is a more potent
      dissolving agent for cholesterol gall stones than MTBE, giving a 40% reduction in
      dissolution time. Addition of dimethylsulphoxide to ethyl propionate does not
      result in faster stone dissolution. MTBE and MTBE/dimethylsulphoxide are far
      superior to ethyl propionate as solvents for cholesterol gall stones.

PMID- 7828993
TI  - Specific interaction of pancreatic elastase and leucocytes to produce oxygen
      radicals and its implication in pancreatitis.
AB  - Many previous reports using experimental animal models of pancreatitis have
      suggested that oxygen free radicals play an important part in initiation and
      development of pancreatitis. Infiltration of inflammatory cells--that is,
      neutrophils, lymphocytes, and monocytes--has been seen in damaged pancreatic
      glands of animal models and patients with pancreatitis. As neutrophils are known
      to be the highest producer of oxygen free radicals among these inflammatory
      cells, it seems plausible that oxygen free radicals produced by neutrophils have
      some pathoaetiological meaning in pancreatitis. This study measured the
      superoxide production by neutrophils obtained from patients with acute and
      chronic pancreatitis and then examined the effects of pancreatic enzymes on
      superoxide production. Patients showed significantly higher superoxide production
      by 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA) stimulated neutrophils
      than healthy controls. Among the three pancreatic enzymes, amylase, trypsin, and
      elastase, elastase was the only one that increased the superoxide production by
      PMA stimulated neutrophils, by an increment of 1.5-fold. It also increased the
      activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase prepared
      from PMA stimulated neutrophils by a factor of 2.1. High affinity and low
      affinity binding sites for elastase on neutrophils were identified. These results
      suggest that elastase plays a part in the development of pancreatitis by
      enhancing superoxide production of neutrophils.

PMID- 7828994
TI  - Distal biliary stricture as a complication of sclerosant injection for bleeding
      duodenal ulcer.
AB  - A patient undergoing repeated endoscopic injection therapy for important bleeding
      from a duodenal ulcer developed intestinal perforation followed by extrahepatic
      obstructive jaundice resulting from benign biliary stricture. It is proposed that
      these complications were a consequence of the use of ethanolamine oleate as part
      of the injection regimen and caution against the use of this material is needed,
      particularly as current clinical trials suggest that sclerosants offer no
      advantage over injection therapy with dilute adrenaline alone.

PMID- 7828995
TI  - Polypoid mucosal prolapse in a pelvic ileal reservoir.
AB  - A case of a patient who developed a polypoid area of mucosal prolapse three and a
      half years after having an ileoanal pouch for ulcerative colitis is presented.
      This seems to be the first published report. This new manifestation of mucosal
      prolapse in a pelvic ileal reservoir underlines that the pouch as a neorectum is
      subject to disorders familiar in the rectum.

PMID- 7828996
TI  - Cap polyposis occurring in the postoperative course of pelvic surgery.
AB  - The case is reported of a 42 year old woman who presented with the characteristic
      clinical, sigmoidoscopic, and histological features of cap polyposis occurring in
      the postoperative course of pelvic surgery. Pathogenesis of cap polyposis is
      unknown. In this patient, abnormal colonic motility was not a likely aetiological
      factor as suggested in previous cases. Despite some arguments favouring an
      infectious origin or participation, no specific viral or bacterial agent was
      identified. Cap polyposis remains a poorly recognised condition, which may be
      confused with inflammatory bowel disease.

PMID- 7828997
TI  - Digestive surgery is a stillborn specialty in the United Kingdom.

PMID- 7828998
TI  - Cancer risk in patients treated surgically for duodenal ulcer.

PMID- 7828999
TI  - Intestinal permeability in patients with Crohn's disease.

PMID- 7829000
TI  - Value of granulocyte scintigraphy in inflammatory bowel disease.

PMID- 7829001
TI  - Benign intracranial hypertension.

PMID- 7829002
TI  - Helicobacter pylori in eastern European countries: what is the current status?

PMID- 7829003
TI  - Paediatric problems in tropical gastroenterology.

PMID- 7829004
TI  - Expression of p53 in early (T1) gastric carcinoma and precancerous adjacent
      mucosa.
AB  - Abnormalities of the tumour suppressor gene p53 have been shown in approximately
      60% of advanced gastric adenocarcinomas and it has been suggested that the
      immunohistochemical finding of increased p53 expression is a prognostic marker in
      gastric cancer. No studies of early (T1) tumours have been reported. Over
      expression of p53 protein in 95 early gastric carcinomas and in adjacent mucosa
      was investigated using immunohistochemistry with antibody CM1. Thirty five per
      cent of the tumours were positive. The frequency of p53 positivity in tumours of
      tubular histological type (46%) was significantly higher than that in signet ring
      tumours (10%) (p = 0.006), and neoplasms that invaded deeply into the submucosa
      were more frequently positive (45%) than others (30%). Five of eight (62%) T1
      tumours with lymph node metastases showed immunoreactive p53. In signet ring
      tumours, immunopositivity correlated with the frequency of DNA aneuploidy. p53
      Over expression was also found in 15% of 26 examples of high grade dysplasia in
      mucosa adjacent to invasive tumours. No positivity was found in intestinal
      metaplasia or in normal mucosa. The findings show that immunocytochemically
      demonstrable over expression of p53 correlates with other morphological markers
      of aggressiveness in T1 gastric adenocarcinoma. The increasing frequency of p53
      immunoreactivity in the sequence of high grade dysplasia-->early gastric cancer-
      >advanced gastric cancer supports the view that abnormalities of p53 are related
      to tumour progression in gastric carcinogenesis.

PMID- 7829005
TI  - Release of vasodilator, but not vasoconstrictor, neuropeptides and of
      enteroglucagon by intestinal ischaemia/reperfusion in the rat.
AB  - Reperfusion of ischaemic intestine is characterised by an initial hyperaemia with
      ensuing mucosal repair. This study investigated possible roles for gut vasoactive
      neuropeptides and trophic peptides in these phenomena. Groups of rats were
      monitored during superior mesenteric artery occlusion for five or 20 minutes,
      with or without subsequent reperfusion for five minutes. Peptide concentrations
      (fmol/ml) in arterial blood, were measured using specific radioimmunoassays.
      Intestinal ischaemia alone did not cause haemodynamic disturbance or peptide
      release. Reperfusion, after five minutes of ischaemia, resulted in arterial
      hypotension and a rise in plasma vasoactive intestinal polypeptide (mean (SEM))
      (37 (3), control 11 (4), p < 0.001). After 20 minutes of ischaemia, reperfusion
      resulted in greater hypotension (p < 0.05) and release of both vasoactive
      intestinal polypeptide (31 (3), p < 0.05 v control) and the more potent
      vasodilator beta-calcitonin gene related peptide (49 (3), control 23 (1), p <
      0.001). By contrast, the vasodilators alpha-calcitonin gene related peptide and
      substance P and the vasoconstrictors neuropeptide Y, peptide YY, and somatostatin
      were not released. Bombesin, a stimulatory neuropeptide, was released after 20
      minutes of ischaemia/reperfusion (13 (2), control 7 (3), p < 0.05). Plasma
      enteroglucagon rose from control (51 (4)) to 110 (16) (p < 0.001) and to 158 (27)
      (p < 0.005) after five and 20 minutes of ischaemia/reperfusion. The potent
      enteric vasodilators vasoactive intestinal polypeptide and beta-calcitonin gene
      related peptide, unopposed by vasoconstrictors, may promote post-ischaemic
      intestinal hyperaemia. The rise in plasma enteroglucagon may point to diffuse
      mucosal injury and is consistent with the putative trophic role of this peptide.

PMID- 7829006
TI  - Enteric protein loss and intestinal permeability changes in children during acute
      shigellosis and after recovery: effect of zinc supplementation.
AB  - The effect of zinc supplementation on intestinal permeability changes and protein
      loss was studied in 32 children aged between 1 and 12 years during bouts of acute
      shigellosis and after recovery. An intestinal permeability test and then a 48
      hour balance study were performed on all patients. They were then blindly
      assigned to receive vitamin B syrup either with or without zinc acetate (15 mg/kg
      per day) for a month. All patients received a five day course of nalidixic acid.
      The balance study was repeated during convalescence and follow up, but a
      permeability test was done only at follow up after one month. Intestinal
      permeability, expressed as a urinary lactulose:mannitol excretion ratio, improved
      significantly (p = 0.001) along with a significant increase (p = 0.005) in
      mannitol excretion in the zinc supplemented children, suggesting a resolution of
      small bowel mucosal damage. The latter was associated with a higher coefficient
      of nitrogen absorption (p = 0.03), suggesting a possible role of zinc in the
      treatment of shigellosis. Enteric protein loss, as assessed by faecal alpha 1
      antitrypsin clearance, was not influenced by zinc supplementation.

PMID- 7829007
TI  - Circulating immunoglobulin G1 antibody in patients with ulcerative colitis
      against the colonic epithelial protein detected by a novel monoclonal antibody.
AB  - Autoimmunity has been implicated in the pathogenesis of ulcerative colitis (UC).
      Several studies have shown amplified immunoglobulin G1 (IgG1) antibody response
      in UC; however the immunoreactive antigen(s) is unknown. To study this
      antigen(s), mucosal colonic extract was prepared by sonication,
      ultracentrifugation followed by ion exchange chromatography in fast protein
      liquid chromatography. The fraction (enriched colonic peptide), that was most
      reactive to a novel monoclonal antibody, 7E12H12 (IgM isotype), was isolated and
      used to examine the immunoreactivity against the patients' serum samples. Two
      hundred and thirteen coded samples from 111 patients with UC (symptomatic and
      untreated (63), symptomatic and treated (26), remission (22)); 47 with Crohn's
      disease (CD) (40 were symptomatic and untreated, and 30 had colonic disease); 29
      with acute diarrhoea caused by specific pathogen(s); 10 with systemic lupus
      erythematosus, and 16 normal subjects were examined against the enriched colonic
      peptide by IgG subtype specific enzyme linked immunosorbent assays (ELISAs).
      Total IgG antibody reactivity was significantly (p < 0.01) higher only in
      symptomatic and untreated UC patients compared with each of the non-UC group, but
      the sensitivity was only 50%. IgG2 and IgG3 reactivities were not different among
      various groups. The IgG1 antibody reactivity against the enriched colonic
      peptide, however, differentiated UC patients from CD and each of the other non-UC
      groups. Seventy nine per cent of the patients with UC, treated or untreated,
      symptomatic or in remission, had significantly (p < 0.0001) higher IgG1 antibody
      against the enriched colonic peptide when compared with each of the other non-UC
      groups. Only 12% of CD serum samples and none of the other control serum samples
      reacted. Using purified serum IgG1 and 7E12H12-IgM, by 7E12H12 reactive peptide
      indeed reacts with UC-IgG1 antibody but not with control IgG1.

PMID- 7829008
TI  - Calcipotriol inhibits rectal epithelial cell proliferation in ulcerative
      proctocolitis.
AB  - Vitamin D3 reduces human rectal crypt cell production rate (CCPR) and may thereby
      protect against colorectal cancer. Cell turnover is increased in ulcerative
      proctocolitis, which might therefore respond to vitamin D3 metabolites. This
      study investigated the effect of calcipotriol, a synthetic vitamin D3 analogue
      that avoids hypercalcaemia, on human rectal CCPR in ulcerative proctocolitis.
      Paired rectal biopsy specimens from seven patients with severe disease were
      established in organ culture with or without calcipotriol (1 x 10(-6) M). After
      15 hours, vincristine (0.6 microgram/ml) was added to induce metaphase arrest,
      and CCPR was determined by linear regression analysis of accumulated metaphases.
      Compared with values in 17 controls with incidental anal conditions, median
      rectal CCPR was 28% higher in ulcerative proctocolitis: 5.90 (5.00-9.50) v 4.80
      (2.85-7.07) cells/crypt/hour (p < 0.01). Calcipotriol reduced CCPR by 62% in
      patients with ulcerative proctocolitis, from 5.90 (5.00-9.50) to 2.21 (0.81-3.22)
      cells/crypt/hour (median with range) p < 0.01. Thus calcipotriol can dampen the
      hyperproliferative state in ulcerative proctocolitis and could have a therapeutic
      role in the control of this inflammatory condition.

PMID- 7829009
TI  - Longterm appraisal of the histological appearances of the ileal reservoir mucosa
      after restorative proctocolectomy for ulcerative colitis.
AB  - Between November 1976 and December 1985, 110 patients had restorative
      proctocolectomy for ulcerative colitis. The histological appearances in the
      reservoir mucosa were followed up in 60 of 109 survivors over 19-173 months
      (median 97). The median number of biopsy specimens taken per patient was six with
      a range of 3-13. These were examined by one pathologist (ICT) unaware of the
      clinical details using a scoring system previously described to assess the degree
      of chronic and acute inflammation. There was a significant correlation between
      the degree of severity of chronic and acute changes (r = 0.6192, p < 0.000001).
      There was no correlation between the severity of inflammation and the following
      variables: preoperative duration of disease, presence of cancer or dysplasia in
      the original operative specimen, extra-alimentary manifestations or the type of
      reservoir. A significant correlation between severe inflammation and male sex was
      found (p < 0.035). The 60 patients could be divided into three groups based on
      the severity and fluctuation of histological inflammation. In group A (n = 27,
      45%) chronic changes were minor and acute inflammation was never seen. In group B
      (n = 25, 42%) chronic changes were more severe and there were transient episodes
      of acute inflammation. In group C (n = 8, 13%) severe chronic and severe acute
      inflammation were constantly present. Differentiation of the three groups had
      clearly occurred within six months from closure of the ileostomy. Patients in
      group C could be identified on histological criteria within weeks of closure of
      the ileostomy and were those exclusively at risk of developing chronic pouchitis.
      Chronic pouchitis never occurred in patients of groups A and B. No case of
      dysplasia was seen. Histological assessment of the reservoir mucosa with in a few
      months after closure of the ileostomy seems to define patients who will and who
      will not subsequently develop pouchitis.

PMID- 7829010
TI  - Depressed T cell reactivity to recall antigens in Crohn's disease before and
      after surgical resection.
AB  - Earlier studies regarding possible primary immune disturbances participating in
      the pathogenesis of Crohn's disease yielded conflicting results. Peripheral blood
      lymphocyte subsets and lymphocyte proliferative responses to five soluble recall
      antigens and to the polyclonal stimulator phythaemagglutinin were therefore
      measured in 17 patients with active Crohn's disease, before and six months after
      surgical resection of the inflamed intestine and in 16 healthy controls.
      Lymphocyte proliferation in response to all five recall antigens was
      significantly lower in patients than in controls. No significant differences with
      controls were detected after surgery. Addition of indomethacin to
      phythaemagglutinin stimulated lymphocyte cultures had a stronger proliferation
      enhancing effect in patients than in controls, resulting in comparable
      proliferative responses in both groups. When both indomethacin and prostaglandin
      E2 were added, inhibition of reactivity by prostaglandin E2 was stronger in
      patients' cultures. This suggests a higher sensitivity to inflammatory
      prostaglandins in Crohn's disease. The degree of lymphocyte stimulation by
      antigens correlated positively with the percentage of circulating memory T cells
      (CD 45 RA-). The percentage of activated (HLA-DR+) CD8 cells was higher in
      patients than in controls. The CD4/CD8 ratio, which was not significantly
      different between patients and controls, correlated significantly with disease
      activity and characteristics, even in the postoperative phase. These findings
      suggest that immune abnormalities in Crohn's disease fluctuate with and are
      probably secondary to inflammatory activity.

PMID- 7829011
TI  - Colonic secretory effect in response to enteral feeding in humans.
AB  - Diarrhoea complicating enteral feeding is a common clinical problem affecting up
      to 25% of patients. Its pathogenesis remains unknown. A new technique of human in
      vivo segmental colonic perfusion was used to investigate colonic water and
      electrolyte movement in response to enteral feeding. Four groups of studies were
      performed in which low and high load polymeric enteral diet infusions were
      undertaken, either intragastrically or intraduodenally (n = 6 each group). Net
      absorption of sodium, chloride, and water occurred during fasting throughout the
      colon in all groups. There was a significant net secretion of sodium, chloride,
      and water in the ascending colon during low load (sodium: -42 mmol/h; 95%
      confidence limits -52 to -19, Chloride: -18 mmol/h; -50 to +16, water: -174 ml/h;
      -348 to -30) and high load (sodium: -24 mmol/h; -60 to +8, chloride: -18 mmol/h; 
      31 to +16, water: -120 ml/h; -246 to +6) gastric feeding, and during high load
      duodenal feeding (sodium: -12 mmol/h; -22 to -6, chloride; -6 mmol/h; -16 to +3,
      water: -72 ml/h; -144 to -6). Net secretion persisted in the distal colon only
      during high load gastric feeding. In the other three groups there was a net
      absorption in the distal colon. This study identified a significant colonic
      secretory response to enteral feeding, which is related to the site and load of
      the diet infusion. This response may play an important part in the pathogenesis
      of enteral feeding related diarrhoea.

PMID- 7829012
TI  - Divergent effects of epidermal growth factor and calcipotriol on human rectal
      cell proliferation.
AB  - Vitamin D may protect against colorectal cancer by reducing cell proliferation
      and inducing differentiation. By contrast, epidermal growth factor (EGF)
      stimulates cell proliferation and may encourage gastrointestinal mucosal healing.
      This study investigated the effect of a synthetic vitamin D analogue,
      calcipotriol, and EGF on human rectal epithelial cell proliferation in patients
      with familial adenomatous polyposis (FAP). In addition, a new technique to
      measure the cell cycle time is described. Sigmoidoscopic biopsy specimens were
      obtained from 14 patients with FAP. Tissue was established in organ culture, with
      or without the addition of EGF (n = 8), or calcipotriol (n = 6). Proliferation
      was determined using (a) metaphase arrest to measure the crypt cell production
      rate, (b) native mitotic index, and (c) the growth fraction using PC10 antibody.
      EGF receptor expression was shown using a polyclonal antibody AP12E. Calcipotriol
      reduced crypt cell production rate by 52% from mean (SEM) 5.29 (1.18) to 2.56
      (0.80) cells/crypt/hour (p < 0.01) and EGF increased crypt cell production rate
      by 102% from 3.62 (0.59) to 7.33 (0.90) cells/crypt/hour (p < 0.05), and this
      tissue expressed the EGF receptor. The growth fraction was 48.40 (4.0)%, and the
      native mitotic index 1.08 (0.14)%. The cell cycle time was estimated as 94.5
      hours and the time for mitosis as one hour. Thus, calcipotriol and EGF have
      divergent effects on human rectal mucosal proliferation.

PMID- 7829013
TI  - Digestibility and bulking effect of ispaghula husks in healthy humans.
AB  - The digestibility of ispaghula, a mucilage from Plantago ovata composed mainly of
      arabinoxylans, and its faecal bulking effect were studied in seven healthy
      volunteers who ingested a low fibre controlled diet plus either placebo or 18
      g/day of ispaghula for two 15 day periods. Whole gut transit time and gas
      excretion in breath and flatus were not different during the periods of ispaghula
      and placebo ingestion. Faecal wet and dry weights rose significantly, however,
      during ispaghula ingestion. Faecal short chain fatty acid concentrations and the
      molar proportions of propionic and acetic acids also increased. Most of the
      ispaghula had reached the caecum four hours after ingestion in an intact highly
      polymerised form. During ispaghula ingestion, the increase in the faecal output
      of neutral sugars was accounted for by the faecal excretion of arabinose and
      xylose in an intact highly polymerised form; the apparent digestibilities of
      these sugars were 24 (11) and 53% (6) respectively (mean (SEM)). In conclusion,
      ispaghula is more resistant to fermentation than previously reported in humans,
      and its bulking effect largely results from intact material.

PMID- 7829014
TI  - Resistance of erythrocytes to lipid peroxidation in alcoholic patients.
AB  - The ability of erythrocytes to resist lipid peroxidation may be a useful marker
      of antioxidant status in alcoholic patients, in whom depletion of dietary
      antioxidants may combine with increased production of free radicals to produce
      liver damage. There are conflicting reports, however, on the resistance of
      erythrocytes from alcoholic patients to lipid peroxidation. This study examined
      the relation between the degree of alcohol induced liver disease and the
      resistance of erythrocytes to chemically induced lipid peroxidation, measuring
      lipid peroxidation as malondialdehyde production. Erythrocytes from alcoholic
      patients with Child's C cirrhosis had significantly increased resistance to lipid
      peroxidation compared with both controls (p < 0.001) and alcoholic patients with
      moderate liver disease (p < 0.001). There was no difference between alcoholic
      patients with moderate liver disease and controls. Increased resistance to free
      radical initiated lipid peroxidation in alcoholic patients is related to liver
      damage rather than to alcohol abuse alone. This could arise from changes in the
      lipid composition of the erythrocyte membranes resulting from abnormal liver
      function. Tests of antioxidant status based upon the resistance of erythrocytes
      to free radical stress in vitro may therefore be flawed when such changes in
      membrane lipid composition can occur.

PMID- 7829015
TI  - Prevention of biliary stent occlusion using cyclical antibiotics and
      ursodeoxycholic acid.
AB  - This study reports an open randomised controlled trial of cyclical antibiotics
      and ursodeoxycholic acid in prevention of plastic biliary stent occlusion.
      Seventy patients with malignant distal bile duct obstruction were randomised to
      either active treatment with cyclical antibiotics (ampicillin, metronidazole,
      ciprofloxacin) and ursodeoxycholic acid or no treatment after successful stent
      insertion. The two groups were well matched. The follow up was complete with
      stent occlusion or death being the end points. There was no difference in the
      incidence of stent occlusion between the two groups and the overall survival was
      similar. In conclusion, this study did not show any benefit of treatment with
      antibiotics and ursodeoxycholic acid in prolonging stent patency or improving
      survival.

PMID- 7829016
TI  - Rapid cholesterol nucleation time and cholesterol gall stone formation after
      subtotal or total colectomy in humans.
AB  - Changes in biliary lipid composition, pH, ionised calcium, total and unconjugated
      bilirubin, and cholesterol nucleation time of gall bladder bile samples were
      examined in six patients who had undergone subtotal or total colectomy between
      five months and seven years previously, and values were compared with those in
      control patients with no gall stones. The colectomy group mainly comprised
      patients with ulcerative colitis and familial adenomatosis coli, in whom only a
      short length of the terminal ileum (mean (SEM) 2.25 (0.57) cm) had been resected.
      The reconstruction procedures were ileoanal anastomosis in two patients, terminal
      ileostomy in two, ileorectal anastomosis in one, and J shaped ileal pouch-anal
      anastomosis in one patient. The distributions of age, sex, and relative body
      weight were similar in the two groups. The gall bladder bile was lithogenic in
      the post colectomy group--these patients had a significantly increased
      cholesterol saturation index (p < 0.01) and rapid cholesterol nucleation time (p
      < 0.05) compared with the control group. A significant increase in the molar
      percentage of cholesterol and a decrease in that of total bile acid associated
      with significantly decreased secondary bile acids (p < 0.05) were observed in the
      post colectomy group. Gall stones formed in two of six patients after colectomy
      were cholesterol stones containing more than 80% cholesterol by dry weight. Total
      and unconjugated bilirubin, pH, and ionised calcium values were similar in the
      two groups. The results indicate that after total or subtotal colectomy the
      composition of gall bladder bile increases the risk of cholesterol gall stone
      formation.

PMID- 7829018
TI  - Complexity and the hepatitis viruses.

PMID- 7829017
TI  - Enteral nutrition and the small intestine.

PMID- 7829019
TI  - Strongyloidiasis.

PMID- 7829020
TI  - Pancreas in end stage renal disease.

PMID- 7829021
TI  - Imaging of the common bile duct.

PMID- 7829022
TI  - [Studies on agonists and antagonists of smooth muscle contraction by the use of
      an actomyosin preparation].
AB  - The sites of action of many chemical agents that modify the contraction of smooth
      muscle are in the smooth muscle membrane. However, a few agents, such as
      calmodulin inhibitors and protein kinase inhibitors, interact directly with
      contractile elements of the actomyosin system so as to modify smooth muscle
      contraction. Here, we describe experimental procedures that are applicable for
      the screening of smooth muscle relaxants with this mode of action. Myosin B was
      extracted from chicken gizzard smooth muscle. Because myosin B was a crude
      preparation of smooth muscle actomyosin, it consisted of regulatory proteins of
      calmodulin, myosin light chain kinase and protein phosphatase in addition to the
      contractile proteins of actin and myosin. Interaction of chemical agents with
      these proteins could be detected by measuring the Mg-ATPase activity of the
      myosin B preparation. Then we examined whether the agents that altered the ATPase
      activity was associated with changes in phosphorylation of myosin light chain. If
      the levels are altered, the agents may interact with the regulatory protein(s).
      If not, the site of their action was in the contractile proteins. The analysis
      with these respective proteins will be also described.

PMID- 7829023
TI  - [Effects of FRG-8813, a new histamine H2-receptor antagonist, on gastric mucus in
      rats].
AB  - We examined the effects of FRG-8813, a new histamine H2-receptor antagonist with
      potent antisecretory activity, on gastric mucus in male SD rats (7w). In this
      study, the effects of FRG-8813 (1, 3, 10 mg/kg), given orally twice a day for 7
      days, were investigated by histochemical and biochemical methods in comparison
      with those of cimetidine (CM, 30 mg/kg) and famotidine (FM, 1 mg/kg) in the
      fundic gland area (F. area) and pyloric gland area (P. area). In the
      histochemical study by alcian blue (pH 2.5)-PAS (AB-PAS) or high iron diamine
      alcian blue (HID-AB) staining, the CM group showed a significant decrease in PAS
      and tended to show decreases in HID-AB positive mucus and mucous gel layer in the
      F. area; the FM group also showed a decrease in AB positive mucus in the P. area.
      On the other hand, the AB-PAS and HID-AB positive mucus of the FRG-8813 group
      were not affected. In the biochemical study, FRG-8813 increased the gastric
      mucosal hexose, hexosamine and sialic acid composing the mucus in a dose
      dependent manner in the F. area. These results suggest that FRG-8813 does not
      cause a decrease in gastric mucus, unlike CM or FM, and it may be able to promote
      mucus secretion through increasing the mucous component in the F. area.

PMID- 7829024
TI  - [The effect of doxorubicin on the unimpeded eruption rates of rat mandibular
      incisors].
AB  - We examined the effects of daily injections of doxorubicin, an anti-tumor drug,
      on unimpeded eruption rates, pulp cells, odontoblasts, periodontal ligament and
      dentine formation in the rat mandibular incisor. The experimental animals were
      intraperitoneally injected with 5 mg of doxorubicin/kg body weight/day for a
      period of 7 days. The eruption rates decreased gradually; and on the seventh day,
      the mean eruption rate had decreased to 14% of the control value. In addition, we
      noticed marked destruction of pulp cells and periodontal cells at the basal
      region of the incisor. The amount of dentine formation was measured using the
      tetracycline labeling method, but significant decreases in dentine formation were
      not observed. These results suggest that destruction of the basal tissues is
      related to inhibition of incisor eruption rates, but that tooth eruption is not
      related to dentine formation.

PMID- 7829025
TI  - [Anticoagulant effect of a single bolus injection of parnaparin sodium (LHG) on a
      hemodialysis model in dogs].
AB  - Hemodialysis was performed on dogs, following intravenous bolus injections of LHG
      at dosage levels of 50, 100 and 200 IU/kg and heparin at the levels of 100 and
      200 IU/kg. LHG exerted dose-dependent anticoagulant effects and prolonged the
      hemodialysis time, compared to heparin with similar anti-Xa activity. When LHG
      was administered, the half-life of plasma anti-Xa activity was longer than that
      of heparin at similar anti-Xa activity. LHG prolonged the activated partial
      thromboplastin time (APTT) linearly and dose-dependently. However, the
      prolongation was much less than that of heparin, and the anticoagulant activity
      of LHG continued even after the APTT returned to the value before LHG
      administration. When LHG was administered, whole blood Xa activated coagulation
      time (XCT) and plasma Xa activated coagulation time (PXCT) were prolonged in a
      significantly greater degree compared to APTT. Therefore, XCT and PXCT were
      considered to be appropriate parameters for monitoring LHG. In the groups
      administered with LHG at 100 and 200 IU/kg, where hemodialysis could be continued
      for 8 hr, the tissue factor pathway inhibitor (TFPI) activity in the plasma
      tended to show a sustained increase. These findings suggested the possibility
      that not only the antithrombin III dependency mechanism but also the TFPI
      mechanism contributed to a longer LHG hemodialysis duration compared to heparin
      administration.

PMID- 7829026
TI  - [Effects of byakushi and ogon on the hepatic drug metabolizing enzymes in rats].
AB  - The effect of single or daily oral administration of hot water extracts (HWE)
      from Byakushi or Ogon on rat hepatic drug-metabolizing enzymes were investigated
      in vivo. Enzymes were measured for 3 to 72 hr after single oral administration of
      HWE at the dose of 1.0 g/kg or 5.0 g/kg. Administration of 1.0 g/kg of Byakushi
      and 5.0 g/kg of Ogon inhibited aniline hydroxylase activity, while 5.0 g/kg of
      Byakushi inhibited it in the early phase, but increased it in the late phase.
      Byakushi inhibited aminopyrine N-demethylase activity, while 5.0 g/kg of Ogon
      increased it. Byakushi and Ogon decreased the amount of cytochrome P-450.
      Byakushi and Ogon increased the amount of cytochrome b5. Byakushi increased
      cytochrome c reductase activity 3 hr after administration and decreased it 6 and
      12 hr after administration. In contrast, 1.0 g/kg of Ogon decreased cytochrome c
      reductase activity, and 5.0 g/kg increased it 6 hr after administration and
      decreased it 12 hr after administration. At 24 hr after the last administration
      to animals treated with a regimen of once a day administration of the HWE (0.1 or
      1.0 g/kg) of Byakushi or Ogon for 14 days, the enzymes were measured. Byakushi
      decreased aminopyrine N-demethylase activity, the amount of cytochrome P-450, and
      cytochrome c reductase activity. Ogon decreased cytochrome c reductase activity.
      Byakushi altered the composition of cytochrome P-450 isozyme after daily
      administration.

PMID- 7829027
TI  - [Extraventricular obstructive hydrocephalus].
AB  - In extraventricular obstructive hydrocephalus (EVOH) there is an impaired outflow
      from the subarachnoid space usually at the level of the basal cisterns or
      arachnoid granulations. Subarachnoid haemorrhage, suppurative meningitis, and
      neoplastic or inflammatory exudates may fibrose or occlude the subarachnoid
      space. Following early reports that the response to shunt procedures was
      universally excellent, CSF shunting operations were performed on a large scale.
      Presence of the typical clinical triad, identified underlying aetiology,
      predominance of gait disorder, short duration of illness, absence of atrophy on
      CCT scan, typical lumboventricular perfusion picture, and improvement after high
      volume lumbar puncture usually predict a beneficial response to surgery. The case
      presented here, however, indicates a favourable outcome of shunt surgery even in
      idiopathic EVOH with long duration of illness and without substantial clinical
      improvement after high-volume lumbar puncture. Thus, in clinically progressive
      idiopathic EVOH, shunt surgery should be considered in spite of a high
      complication rate, since there are no promising therapeutic alternatives for this
      syndrome.

PMID- 7829028
TI  - [Neuropsychological analysis of transitory partial performance disorders. A video
      and MRI supported study].
AB  - Apraxia is an impairment of voluntary movements not caused by paresis, sensory
      deficits or aphasia. It appears mainly after left-hemispheric parietal or
      callosal lesions. Our patient had a temporary apraxia that could be correlated
      with the development of the perifocal area around a left parietooccipital
      cerebral bleeding. These neuropsychological disorders belonged to the development
      and the disappearance of the perifocal area as seen via several MRI.

PMID- 7829029
TI  - [Paranoid hallucinatory psychoses as the first manifestation of HIV infection].
AB  - All parts of the central nervous system may be involved in HIV infection,
      resulting in a variety of neuropsychiatric syndromes some of which resemble
      functional psychoses. Corresponding to the HIV-associated disease these syndromes
      differ in course and severity. A very common form is the AIDS-dementia complex,
      especially late in the course of disease. Up to now, however, a specific therapy
      is not available. A case of severe psychosis with paranoid delusions and
      hallucinations in a patient with otherwise asymptomatic HIV infection is
      reported. From her biography it was concluded that the infection occurred 10
      years earlier. During therapy with azidothymidine, symptoms disappeared within 3
      months, and more than one year after admission to our hospital the patient was
      still able to work. According to the course of the disease in this patient,
      reports from the literature and pathogenetic theories, an early therapy with
      antiviral agents is recommended in HIV-induced subacute encephalitis.

PMID- 7829030
TI  - [Clinical diagnosis and therapeutic possibilities for dementia of the Alzheimer
      type].
AB  - This review article tries to define some guidelines how to proceed in the
      clinical diagnosis of Alzheimer's disease. In addition, the article will discuss
      presently available pharmacological and nonpharmacological treatments of this
      disease. The first part of the article will describe diagnostic measures
      (physical and neuropsychological examination, test manuals, laboratory and
      apparative tests), and which order of sequence should be observed. Special
      attention is paid to disorders different from Alzheimer's disease and to take
      care not to overlook dementia syndromes which can be treated. In the second part
      of the article, therapeutic strategies, both pharmacological and
      nonpharmacological ones, are mentioned. Approaches to treatment of cognitive core
      symptoms and treatment strategies with regard to secondary psychiatric symptoms
      which may occur in Alzheimer's disease are discussed.

PMID- 7829031
TI  - [Persisting psychological disorders following harrassment because of an
      application to leave the GDR].
AB  - In an exploratory study we examined 40 patients, who had been exposed to
      harassment in the GDR because of an official application to leave and who
      suffered from persisting mental sequelae of that experience. On an average more
      than six years after termination of the stress situation in the GDR, patients
      showed a moderate anxious-depressive syndrome and vegetative complaints.
      Diagnostic classification varied; depressive disorders, posttraumatic stress
      disorder, somatoform and anxiety disorders were most often diagnosed. 45% of the
      patients stated that the symptoms were not mainly due to experiences during
      repression, and 43% saw a mainly positive effect of that experience on their
      life. The relevance of the findings is discussed briefly.

PMID- 7829032
TI  - [The call of Viktor von Weizsackers to the chair for neurology in Breslau 1941].
AB  - Only five chairs especially for neurology were existing in Germany in 1938. In
      this paper the history of the call of Viktor von Weizsacker (1886-1957) to the
      famous Breslau chair (Otfrid Foerster) in 1941 is described in detail using
      unpublished material from the Reichsministerium fur Wissenschaft, Erziehung und
      Volksbildung.

PMID- 7829033
TI  - The hospice clinician's response to euthanasia/physician assisted suicide.

PMID- 7829034
TI  - Patient and physician characteristics affecting the choice of home based hospice,
      acute care inpatient hospice facility, or hospitals as last site of care for
      patients with cancer of the lung.
AB  - In this exploratory study we found that in 1986, in Clark County, Nevada, home
      based hospice services were utilized at a very limited level for lung cancer
      patients. A nontraditional acute care hospice facility, however, was heavily
      utilized; but only slightly less so than community hospitals. Using death
      certificate and state cancer registry data, we explored several factors affecting
      these choices of sites of treatment of the last episode of illness. Among them
      were sociodemographic characteristics of patients, physicians' specialty, and
      volume of patients with terminal cancer of the lung. The findings and hypotheses
      lend support to further studies of the most cost effective last site of care for
      terminal lung cancer. The need for an ongoing examination of the impact of public
      policy on the definition of hospice and careful consideration of nontraditional
      models is indicated.

PMID- 7829035
TI  - Hospice care for patients living alone: results of a demonstration program.
AB  - The Wissahickon Hospice initiated a demonstration program in 1988 to provide home
      hospice care to individuals living at home without primary care persons. This
      paper describes the planning process and admission requirements for the Live
      Alone Program and the evaluation results for 34 Live Alone patients compared to
      105 regular hospice patients. Principal findings were that the hospice was able
      to maintain patients at home, to provide care safely to patients, and to enable
      home deaths for patients living alone. Patients living alone tended to require
      more supportive services than regular patients and to incur higher patient care
      costs.

PMID- 7829036
TI  - Law and psychiatry in America over the past 150 years.
AB  - American forensic psychiatry was founded in 1838 with the publication of Isaac
      Ray's Treatise on the Medical Jurisprudence of Insanity. Ray's ideas were
      influential in the early history of forensic psychiatry but were overlooked in
      the formulation of the M'Naghten Rules in England, an early parliamentary effort
      to define criteria for the insanity defense. In the mid-1800s, asylum-based
      psychiatrists formulated model laws addressing involuntary commitment and debated
      the definition of mental illness for legal purposes. In the late 1800s, courts
      became interested in findings of brain pathology in insanity defense cases, and
      neurologists joined psychiatrists as expert witnesses. Beginning around 1950,
      increased judicial activism led to a new standards for insanity in criminal
      cases, advances in the civil rights of mentally ill persons, and refinements in
      the role of expert witnesses. In 1969 forensic psychiatrists established a
      professional organization, and board certification in the subspecialty began in
      1979.

PMID- 7829037
TI  - Reflections on antipsychiatry and stigma in the history of American psychiatry.
AB  - The author presents his perspectives on the relationship between antipsychiatry
      and the stigma of mental illness. Stigma has existed at least since biblical
      times, when madness as demonic possession and punishment for sin became codified
      in religious belief and practice. The antipsychiatry movement dates from the 18th
      century, when psychiatry first emerged as a medical specialty and the first
      mental hospitals were built. Over the years psychiatry has been a target for
      antipsychiatry groups competing for influence or authority over the mentally ill.
      At various times these groups have included neurologists, social workers, new
      religions, consumers, and psychiatrists themselves. Their common ground has been
      objection to psychiatry as a hospital-centered medical specialty legally
      authorized to institutionalize and treat patients. In the late 19th century,
      treatment of hospitalized patients increased the stigma of mental illness and
      provided fuel for the antipsychiatry movement. During that period psychiatrists
      began to see heredity as the cause of mental illness, became pessimistic about
      restoring patients to sanity, and adopted essentially a custodial approach to
      care that included use of physical restraints. However, recent advances in
      biological treatments have undercut antipsychiatry and rekindled optimism about
      recovery that may go far in eliminating stigma.

PMID- 7829038
TI  - A century and a half of psychiatric rehabilitation in the United States.
AB  - Psychiatric rehabilitation, which is aimed at helping persons who have long-term
      mental illness to develop their capacities to the fullest possible extent, has
      been an integral part of psychiatric treatment in the U.S. since the beginnings
      of moral treatment in the early 19th century. The author outlines broad
      historical developments and prominent current modalities and models of
      psychiatric rehabilitation, including the introduction of family care, the day
      hospital, social skills training, psychoeducation, and the Fountain House model.
      He discusses the conceptual underpinnings of the field, such as the need to work
      with the healthy part of the patient and changes in views on vocational
      rehabilitation. Current concerns include the possibility of overselling
      rehabilitation and of misusing the term "recovery."

PMID- 7829039
TI  - A psychiatric hospital 100 years ago: I. A comparative study of treatment
      outcomes then and now.
AB  - OBJECTIVE: The authors' goal was to compare distribution of diagnoses, length of
      stay, and readmission rates for every 16th patient admitted to the St. Louis
      County Insane Asylum (now St. Louis State Hospital) between 1886 and 1904 with
      those for every 16th patient admitted to the hospital between 1978 and 1980.
      METHODS: A sample of 369 cases was drawn from the archival admission records, and
      380 cases were selected from recent admissions. Descriptive data from the
      archival records were used to make DSM-III diagnoses. Data on length of stay and
      number of readmissions were collected from case records. RESULTS: The historical
      sample had fewer cases of major mental illness, longer mean lengths of stay, and
      fewer mean readmissions than the modern sample. CONCLUSIONS: Differences in the
      clinical characteristics of the two samples may be explained by differences
      between the two periods in treatment philosophies, admitting policies, and
      presence of alternative resources for accommodating long-term chronic patients.

PMID- 7829040
TI  - A psychiatric hospital 100 years ago: II. Patients, treatment, and daily life.
AB  - Data from archival sources were used to determine the kinds of patients treated
      at the St. Louis City (later St. Louis County) Insane Asylum, the treatments they
      received, activities of daily life in the asylum, and political factors affecting
      operation of the asylum in the late 19th and early 20th centuries. Data from
      patient records, journal and newspaper articles, and annual reports of asylum
      superintendents from the period were analyzed. The authors conclude that although
      much has changed in the operation of public psychiatric hospitals in the past 100
      years, some themes, including inappropriate referrals of forensic cases to
      psychiatric hospitals, problems of discharging long-stay patients, and the
      media's tendency to sensationalize events and conditions in hospitals, remain the
      same.

PMID- 7829041
TI  - Homeopathy and the treatment of mental illness in the 19th century.
AB  - In the 19th century, when bleeding and purging were widely used in mainstream
      medicine, homeopathy was warmly embraced by some U.S. practitioners as a more
      humane alternative. Developed by the German physician Samuel Hahnemann,
      homeopathy sought to cure symptoms of disease by use of drugs that induced
      similar symptoms and restored the patient's "vital force." This paper describes
      the general principles of homeopathy and recounts specific treatments of mental
      illness from the homeopathic literature. It also describes the application of
      homeopathic principles to the institutional care of mental illness, using New
      York's Middletown Homeopathic Asylum for the Insane as an example.

PMID- 7829042
TI  - Four decades of mental health trends: an empirical analysis of Hospital and
      Community Psychiatry.
AB  - OBJECTIVE: The authors examined important trends and developments within the
      mental health field since the 1960s as reflected in articles published in
      Hospital and Community Psychiatry. METHODS: A total of 798 articles were
      reviewed, representing all contributions to the journal in 1962, 1967, 1972,
      1977, 1982, 1987, and 1992. Articles were classified into one of six categories,
      and empirical research articles were further classified by primary topic. In
      addition, all articles were indexed by primary setting (hospital, community, or
      both); academic credentials and gender of first author, and economic or public
      policy focus. RESULTS: The number and percentage of empirical research articles
      increased over time, while articles describing programs and professional roles
      declined. Some changes were observed in the primary topics of empirical research.
      Other findings reflect a shift in the setting of articles from hospitals to the
      community and a growth in the percentage of women who were first authors and of
      authors with a Ph.D. degree. CONCLUSIONS: The documented growth of empirical
      research in psychiatry suggests a greater emphasis on methodological rigor in the
      design and implementation of mental health services. Moreover, increases noted in
      scholarly contributions by women and nonmedical professionals indicate a
      broadening of disciplinary perspective over time that is likely to strengthen
      psychiatric research and services.

PMID- 7829043
TI  - Alcohol abuse and Alzheimer's disease.

PMID- 7829044
TI  - National Depression Screening Day: the San Diego experience.

PMID- 7829045
TI  - Computerized TD reminders.

PMID- 7829046
TI  - Clozapine-related priapism.

PMID- 7829047
TI  - Employment relations in the nineties.

PMID- 7829048
TI  - Who's on trial? Multiple personalities and the insanity defense.

PMID- 7829049
TI  - On alleged "remission" from severe bipolar disorder.

PMID- 7829050
TI  - The Monica tapes: recording a 40-year developmental study.

PMID- 7829051
TI  - An analysis of the two-class system of care in public and private psychiatric
      hospitals.

PMID- 7829052
TI  - A retrospective view of the affiliation of occupational therapy and psychiatry.

PMID- 7829053
TI  - The "God of the dance": treating Nijinsky's manic excitement and catatonia.

PMID- 7829054
TI  - Trends in the development of psychiatric services, 1844-1994.
AB  - Over the past 150 years, support for providing appropriate services for mentally
      ill persons has waxed and waned. In colonial America, mentally ill persons were
      institutionalized in jails or almshouses. In the 18th and 19th centuries, asylums
      constituted the primary psychiatric service. Only in the late 19th and early 20th
      centuries did alternatives to long-term hospitalization appear. The mental
      hygiene movement of the early 20th century and the community mental health
      centers movement of the 1960s and 1970s both increased the number of services and
      introduced new types of services. Today, however, despite hopeful signs of
      reduced public prejudice against mentally ill persons, a new "dark age" for
      support of psychiatric services may be dawning, as negative attitudes about
      mental illness continue to drive public policy.

PMID- 7829055
TI  - Issues in American psychiatry reflected in remarks of APA presidents, 1844-1994.
AB  - OBJECTIVE: The author reviewed the history of American psychiatry for the first
      150 years of the American Psychiatric Association's existence (1844-1994) as
      reflected in remarks of the association's presidents. METHODS: Presidential
      addresses or remarks from alternative sources were located for the 120 presidents
      who served the association between 1844 and 1994. RESULTS: The presidents'
      remarks on six topics-psychiatric practice, etiology of mental illness, public
      mental hospitals, alternatives to state hospitals (deinstitutionalization),
      biologic treatments, and fiscal issues were sampled and arranged chronologically.
      CONCLUSIONS: American psychiatry's history--its innovations, cyclical
      repetitions, and self-assessments-can be gleaned from this form of data. The
      presidents' remarks appear to refute the claim that organized American psychiatry
      has been negligent in criticizing itself.

PMID- 7829056
TI  - Organization of Mhc class II B genes in the zebrafish (Brachydanio rerio).
AB  - Using three genomic phage libraries, we isolated 26 clones from the zebrafish MHC
      class II B region. By restriction mapping, the clones could be arranged into six
      clusters, most clusters consisting of several overlapping clones. The combined
      clusters cover a total of 161 kb of the zebrafish class II region. Hybridization
      with specific probes demonstrated the presence in the clusters of two class II A
      and six class II B genes. Sequencing of the B genes revealed that they
      represented six different families of class II loci. Only two of the class II B
      and one of the class II A genes are complete; the others are truncated
      pseudogenes. Only one of the class II B loci shows extensive restriction fragment
      length polymorphism. This is also the only locus found to be transcribed in
      organs with large numbers of lymphoid or myeloid cells. The zebrafish class II
      genes have promoter regions with sequence elements found previously in mammalian
      genes and known to be involved in regulation of expression. The exon-intron
      organization of the zebrafish class II genes is similar to that of the mammalian
      genes, but the introns are characteristically short, ranging in length from 74 to
      362 bp. The distances between A and B genes in a given pair are also short, but
      the distances between B genes are as long as or longer than those between
      mammalian class II B genes. All of the zebrafish class II B genes appear to have
      arisen by duplication and diversification of a single ancestral B gene after the
      separation of bony fishes from other vertebrate taxa.

PMID- 7829057
TI  - Integrated mapping analysis of the Werner syndrome region of chromosome 8.
AB  - The Werner syndrome locus (WRN) is located at 8p11-p12. To facilitate eventual
      cloning of the WRN gene, a 10,000-rad radiation-reduced hybrid (RH) cell panel
      was generated to map genetic markers, sequence-tagged sites (STSs), and genes in
      this region. A hamster cell line carrying an intact human chromosome 8 was fused
      with another hamster cell line. Two sets of hybrid cell panels from 2 separate
      fusions were generated; each panel consisted of 50 independent clones; 33 and 34
      cell lines from the 2 fusions retained human chromsome material as determined by
      inter-Alu PCR. The combined panel was genotyped for 52 markers spanning the
      entire chromosome, including 10 genes, 29 anonymous polymorphic loci, and 13
      STSs. Seventeen of these markers have not been previously described. Markers near
      the centromere were retained at a higher frequency than more distal markers.
      Fluorescence in situ hybridization was also used to localize and order a subset
      of the markers. A RH map of the WRN region was constructed using a maximum
      likelihood method, giving the following most likely order: D8S131-D8S339 (GSR)
      D8S124-D8S278-D8S259-(D8S71)-D8S283- D8S87-D8S105-D8S135 (FGFR1)-D8S135PB-D8S255
      ANK1. A genetic map of 15 short tandem repeat polymorphic loci in the WRN region
      was also constructed. The marker orders from the genetic and RH maps were
      consistent. In addition, an integrated map of 24 loci in the WRN region was
      generated using information from both genetic and RH mapping methods. A 1000:1
      framework map for 6 loci (LPL-D8S136-D8S137-D8S87-FGFR1-ANK1) was determined by
      genetic mapping, and the resulting locus order was fixed during analysis of the
      RH genotype data. The resulting integrated map contained more markers than could
      confidently be ordered by either genetic or RH mapping alone.

PMID- 7829058
TI  - DXS106 and DXS559 flank the X-linked dystonia-parkinsonism syndrome locus (DYT3).
AB  - The locus (DYT3) underlying the X-linked dystonia-parkinsonism syndrome (XDP) was
      delineated within proximal Xq12-Xq13.1 by analysis of linkage, allelic
      association, and haplotypes. Short tandem repeat polymorphisms at loci DXS227,
      DXS559, DXS453, DXS106, DXS339, and DXS135 were studied. The occurrence of a
      recombination within a three-generation family established DXS559 as the distal
      flanking marker of DYT3. /phi/ and /delta/ values were determined as indicators
      of the degree of allelic association between DYT3 and the six marker loci. In
      addition, haplotype analysis was performed at the loci studied. The findings
      establish DXS106 as the proximal flanking marker of DYT3. Given an approximate
      distance between DXS106 and DXS559 of 3.0 Mb, isolation of DYT3 is now feasible
      by positional cloning techniques.

PMID- 7829059
TI  - Multiple loci affect genetic predisposition to hepatocarcinogenesis in mice.
AB  - The C3H/He mouse represents a good experimental model of genetic predisposition
      to hepatocellular tumor development. We analyzed an interspecific test-cross
      population of 106 urethane-treated male (C3H/He x Mus spretus) x C57BL/6J mice,
      typed with 222 genetic markers to locate precisely the hepatocellular tumor
      susceptibility (Hcs) loci. Three regions, on chromosomes 2, 5, and 19, showed a
      significant linkage with hepatocellular tumor development, as indicated by
      different quantitative indexes estimating liver tumor size. Liver tumor frequency
      was not genetically controlled. These loci are different from three other Hcs
      loci that we have previously mapped in an F2 progeny of the C3H/He mouse crossed
      with the resistant laboratory strain A/J. The present result indicates a
      multigenic model of inheritance for hepatocellular tumor susceptibility.

PMID- 7829060
TI  - Use of an intron polymorphism to localize the tropoelastin gene to mouse
      chromosome 5 in a region of linkage conservation with human chromosome 7.
AB  - The complete coding sequence for mouse tropoelastin was obtained from overlapping
      reverse transcriptase polymerase chain reaction (PCR) amplimers. These cDNA
      fragments were derived from mouse tropoelastin mRNA using PCR oligomers
      complementary to conserved domains within rat tropoelastin mRNA. A comparison of
      coding domains of mouse and rat tropoelastin mRNA revealed a greater than 93%
      homology at the nucleotide level and over 96% similarity in the predicted amino
      acid sequence. PCR primers complementary to regions of the mouse tropoelastin
      mRNA were used to define a novel intron length polymorphism (ILP) within intron 8
      of the mouse tropoelastin gene (Eln). This ILP proved to be informative in an
      interspecific backcross in which genomic DNA samples from 75 backcross mice were
      used to map the tropoelastin gene to a position in the distal half of mouse
      chromosome 5. The linkage and genetic distances between Eln and the closest
      molecular markers used in this study are centromere-D5Mit95, D5Mit96-6.7 cM-Gus,
      Eln-4.0 cM-Zp3-telomere.

PMID- 7829061
TI  - Physical map of mouse chromosome 17 in the region relevant for positional cloning
      of the Hybrid sterility 1 gene.
AB  - Hybrid sterility 1 (Hst1) is the major gene responsible for sterility of male
      hybrids between Mus musculus and certain laboratory strains. Thus, Hst1 is of
      importance in studying both postreproductive isolation of closely related species
      and male fertility. It has been mapped to mouse chromosome 17 in the region
      corresponding to the third inversion of the t haplotypes. The aim of the present
      study was to construct a physical map of the Hst1 region as the first step in an
      effort to clone the gene. Three yeast artificial chromosome (YAC) libraries
      (Princeton, Whitehead, and ICRF) were screened with polymerase chain reaction
      (PCR) oligonucleotide primers and DNA probes specific for loci previously mapped
      into the region of the third inversion. The isolated YAC clones were restriction
      mapped and arranged into contigs. Sixteen YAC clones were arranged into a single
      contig encompassing a region approximately 2000 kb long based on restriction
      mapping of highly overlapping but independently derived YAC clones. Five new loci
      in the region of the third inversion were mapped and the order and approximate
      physical distances of 12 loci established in this contig. The Hst1 gene maps
      approximately 0.2 cM proximal to the D17Ph1 locus encompassed by the YAC contig.
      Since the contig extends at least 1200 kb proximal to D17Ph1, it should contain
      the Hst1 gene.

PMID- 7829062
TI  - Comparative analysis of human DNA variations by fluorescence-based sequencing of
      PCR products.
AB  - Automated, direct cycle sequencing of purified double-stranded PCR products using
      Taq polymerase and fluorescently labeled dideoxynucleotide terminators provides a
      robust and highly reproducible method for identifying DNA sequence variations in
      sequence-tagged sites. We describe a simple and sensitive strategy that reliably
      detects the presence of DNA variations when sequencing traces from several
      different individuals are compared. We also demonstrate the use of this strategy
      to estimate allele frequencies of single nucleotide substitutions in a
      population. Taken together, this approach provides an automated method for
      conducting rapid population studies of candidate gene regions that are in linkage
      or association with a specific disease and for comparative evolutionary analysis
      of selected regions of the human genome.

PMID- 7829063
TI  - Comparative mapping of lipocalin genes in human and mouse: the four genes for
      complement C8 gamma chain, prostaglandin-D-synthase, oncogene-24p3, and
      progestagen-associated endometrial protein map to HSA9 and MMU2.
AB  - The lipocalin superfamily encompasses a large set of quite distantly related
      proteins that act as carriers for small, lipophilic molecules. The lipocalin
      genes coding for orosomucoid, the alpha 1-microglobulin/bikunin precursor, and
      the major urinary protein map to MMU4, while their human counterparts map to the
      homologous HSA9q34 area where three other lipocalin genes for complement C8 gamma
      chain (C8G), progestagen-associated endometrial protein (PAEP), and prostaglandin
      D synthase (PTGDS) are also located. By linkage analyses in an interspecific
      backcross progeny in mouse, the Lcn2 gene coding for the oncogenic lipocalin
      24p3, as well as the 3 lipocalin genes for C8G, PTGDS, and PAEP, have now been
      assigned to MMU2. The first three genes map to proximal MMU2, which is known to
      be homologous to HSA9q34. Paep is more distally located, which extends the number
      of regions with conserved syntenies between HSA9q34 and MMU2. By in situ
      hybridization, the human LCN2 gene maps to HSA9q34. Our data indicate that the
      lipocalin locus arrangement in the human/mouse ancestor is closer to that found
      at HSA9q than to that in the MMU genome.

PMID- 7829064
TI  - Large-scale genomic comparison using two-dimensional DNA gels.
AB  - Two-dimensional electrophoresis (2DE) of DNA fragments, in which separation
      occurs first by size and then by sequence variation, is a method enabling large
      scale comparison of complex genomes. Combining 2DE with probing for various
      classes of repetitive genomic elements allows rapid and efficient comparison of
      thousands of fragments and millions of base-pairs of DNA distributed across most
      genomic regions. This approach is demonstrated here by analyzing the extent of
      genomic relatedness of different inbred strains of mice. Such strains are shown
      to differ from each other by approximately 0.2-1% of their nucleotides, above
      which level reproductive speciation occurs. The 2DE method of assessing the
      overall relationship between two genomes represents an appropriate tool for
      analyzing members of a single species, but is too sensitive for use in
      interspecies comparisons.

PMID- 7829065
TI  - Mapping of human immunoglobulin heavy chain variable gene segments outside the
      major IGH locus.
AB  - Physical mapping of the human immunoglobulin heavy chain gene cluster (IGH) on
      chromosome 14 has previously shown that the locus includes at least 63 variable
      region (VH) gene segments. Fifteen VH gene segments are located on six NotI DNA
      restriction fragments that are not within the mapped region of IGH. We have used
      human/rodent somatic cell hybrid lines to map these gene segments, as it was
      previously not proven that they are located in the chromosome 14 IGH locus. Four
      gene segments map to human chromosome 16 and two to chromosome 15. Apparently,
      four of the six NotI fragments, representing 11 VH gene segments, are not located
      within the chromosome 14 IGH locus. In addition, we have demonstrated that a YAC
      containing a functional human telomere, and mapping to 14qter, is located at the
      telomeric end of the IGH gene cluster physical map and contains at least four VH
      gene segments. This YAC is collinear with the existing physical map of genomic
      DNA. We conclude that our original physical map of IGH represents almost the
      entire locus on chromosome 14 and that the 11 gene segments newly mapped are not
      part of the functional IGH locus.

PMID- 7829066
TI  - The genes encoding alpha 2(IX) collagen (COL9A2) map to human chromosome 1p32.3
      p33 and mouse chromosome 4.
AB  - We have determined the chromosomal locations of the human and murine genes coding
      for alpha 2(IX) collagen, a polypeptide subunit of the heterotrimeric type IX
      collagen molecule. COL9A2 was mapped to human chromosome 1p32.3-p33 using
      fluorescence in situ hybridization. A single-strand conformational polymorphism
      within the murine Col9a2 gene was used to map this locus to mouse chromosome 4.
      We also present new sequence data, which completes the coding information for the
      human alpha 2(IX) chain and revises the sequence for the chicken alpha 2(IX)
      chain. This permits comparison of the carboxyl-terminal (NC1) domains of the
      alpha 1(IX), alpha 2(IX), and alpha 3(IX) chains across several species.

PMID- 7829067
TI  - Localization of the VHR phosphatase gene and its analysis as a candidate for
      BRCA1.
AB  - The VH1-related human protein (VHR) gene was localized to human chromosome 17q21
      in a region thought to contain the BRCA1 locus, a locus that confers
      susceptibility to breast and ovarian cancer. VHR encodes a phosphatase with dual
      specificity for tyrosine and serine residues. Thus it is a plausible candidate
      for a tumor suppressor gene such as BRCA1. To test this possibility, the VHR
      coding sequence was screened in individuals with familial breast cancer and in
      sporadic breast tumor and breast cancer cell lines. No mutations were detected,
      suggesting that the VHR gene is not BRCA1.

PMID- 7829068
TI  - Analysis of recombinational hot spots associated with the p haplotype of the
      mouse MHC.
AB  - Most of the recombination events detected within the major histocompatibility
      complex (MHC) of the mouse fall into areas of limited physical size that have
      been designated recombinational hot spots. One of these hot spots, associated
      with the Ea gene, appears to be active only in the presence of the p haplotype of
      the MHC. To study the regulation of the Ea recombinational hot spot and its
      haplotype specificity, a high-resolution comparative map of the MHC and adjacent
      regions was completed in four different backcrosses carrying the p haplotype.
      This mapping study utilized a total of 29 PCR-based molecular markers, including
      7 newly developed markers spanning the region between Pim1 and D17Mit11 on
      Chromosome 17. The analysis of a total of 1093 backcross animals: (1) revealed
      that the presence of the p haplotype of the MHC is not sufficient to induce
      recombination at the Ea hot spot in a dominant manner, and (2) resulted in the
      definition of a new intra-MHC recombinational hot spot between the Tnfb and the
      H2-D genes.

PMID- 7829069
TI  - Genetic map of the fused locus on mouse chromosome 17.
AB  - Fused (Fu) is a dominant mutation in mice resulting in the asymmetry and fusion
      of tail vertebrae in heterozygotes. Fu/Fu homozygotes are often viable and can
      exhibit a duplication of the terminal tail vertebrae resulting in bifurcated
      tails. There are two more severe alleles at Fu, Kinky (FuKi) and Knobbly (FuKb),
      which die between 9 and 10 days of gestation as homozygotes, exhibiting a
      duplication of the embryonic axis, leading to incomplete or complete twinning. To
      define the precise map position of the FuKi mutation on mouse Chromosome 17, a
      983-animal (FuKi tf x Mus spretus)F1 x +tf/+tf interspecific backcross was
      generated and scored for FuKi, another tightly linked visible marker tufted (tf),
      and five linked molecular loci, D17MIT18, D17Leh54, D17Aus57, Hba-ps4, and Pim1.
      The order and genetic distances between the markers were determined to be
      centromere-D17MIT18-5.79 cM-D17Leh54-0.85 cM-D17Pri6-0.12 cM-D17Pri7-0.12 cM-Hba
      ps4-1.20 cM-D17Pri8-0.48 cM-tf-2.05 cM-Pim1. The FuKi gene could not be
      genetically separated from three molecular markers, D17Pri6, D17Pri7, and Hba
      ps4. Yeast artificial chromosome clones that contain these tightly linked markers
      have been isolated to form a contig that contains FuKi. Recombination breakpoints
      generated through the interspecies backcross were mapped onto the contig and
      demonstrate that recombination in this region is not random.

PMID- 7829070
TI  - Beware of using small statistical samples when assessing the quality of a DNA
      library.
AB  - DNA libraries often contain very large numbers of clones (from 1000 up to
      700,000). Since at present it is impossible to analyze all of these clones,
      usually statistical samples comprising less than 100 clones are tested. The
      quality of the library is then assessed by linear extrapolation. Occasionally,
      full coverage of chromosomal regions by DNA probes is inferred from this.
      However, this may not be accurate since linear extrapolation is misleading and
      the statistical samples are generally too small to characterize the libraries. A
      quantitative model of the distribution of the frequencies of the clones in a
      library is mandatory for any useful assessment of the quality of the library.
      Otherwise, it is very difficult to draw useful conclusions from moderately sized
      samples. Examples from everyday life and formulas are given to determine the
      quality of a library and useful sample sizes.

PMID- 7829071
TI  - The genome reconstruction manager: a software environment for supporting high
      throughput DNA sequencing.
AB  - A new software system designed for use in high-throughput DNA sequencing
      laboratories is described. The Genome Reconstruction Manager (GRM) was developed
      from requirements derived from ongoing large-scale DNA sequencing projects.
      Object-oriented principles were followed in designing the system, and tools
      supporting object-oriented system development were employed for its
      implementation. GRM provides several advances in software support for high
      throughput DNA sequencing: support for random, directed, and mixed sequencing
      strategies; a novel system for fragment assembly; a commercial object data-base
      management system for data storage; a client/server architecture for using
      network computational servers; and an underlying data model that can evolve to
      support fully automatic sequence reconstruction. GRM is currently being deployed
      for production use in high-throughput DNA sequencing projects.

PMID- 7829072
TI  - Toward a whole cDNA catalog: construction of an equalized cDNA library from mouse
      embryos.
AB  - The construction of a cDNA library containing all genes without redundancy is one
      of the major technical challenges for biology. Toward this goal, we have
      developed an equalized (normalized) cDNA library from mRNA pools derived from
      mouse embryos that cover the entire period of mouse ontogenesis. Colony
      hybridization analyses with 11 genes showed the reduction of abundance variation
      from at least 6000-fold in the unequalized S-library to approximately 33-fold in
      the EIII-library, which was constructed after three cycles of equalization
      procedure. Limiting dilution PCR analyses with 26 tissue-specific genes showed
      the reduction of abundance variation from at least approximately 1,000,000-fold
      in the S-cDNA mixture to approximately 100-fold in the EIII-cDNA mixture. Based
      on these analyses, we estimate that at least 15,000 independent cDNA clones are
      included with little redundancy in the EIII-cDNA library. This will be a useful
      resource for mouse biology as well as the mouse genome project.

PMID- 7829073
TI  - An ordered NotI fragment map of human chromosome band 11p15.
AB  - An ordered NotI fragment map containing over 60 loci and encompassing
      approximately 17 Mb has been constructed for human chromosome band 11p15. Forty
      two probes, including 11 NotI-linking cosmids, were subregionally mapped to 11p15
      using a subset of the J1-deletion hybrids. These and 23 other probes defining
      loci previously mapped to 11p15 were hybridized to genomic DNA digested with NotI
      and 5 other infrequently cleaving restriction enzymes and separated by pulsed
      field gel electrophoresis. Thirty-nine distinct NotI fragments were detected
      encompassing approximately 85% of the estimated length of 11p15. The predicted
      order of the gene loci used is cen-MYOD1-PTH-CALCA-ST5-RBTN1-HPX-HBB-RRM1 
      TH/INS/IGF2-H19-CTSD-MUC2-DRD4-HRAS - RNH-tel. This map will allow higher
      resolution mapping of new 11p15 markers, facilitate positional cloning of disease
      genes, and provide a framework for the physical mapping of 11p15 in clone
      contigs.

PMID- 7829074
TI  - Human mitochondrial 3,2-trans-enoyl-CoA isomerase (DCI): gene structure and
      localization to chromosome 16p13.3.
AB  - A key enzyme in the mitochondrial beta-oxidation of unsaturated fatty acids is
      the 3,2-trans-enoyl-CoA isomerase (DCI; EC 5.3.3.8). It catalyzes the
      transformation of 3-cis and 3-trans intermediates arising during the stepwise
      degradation of all cis-, mono-, and polyunsaturated fatty acids to the 2-trans
      enoyl-CoA intermediates. A genomic clone encoding the human DCI was isolated and
      characterized by use of the previously cloned human DCI cDNA. The entire gene
      encompasses approximately 12.5 kb, and the coding sequence is distributed over
      seven exons. One major and three minor transcription start sites were determined
      by primer extension analysis. In common with promoters of other housekeeping
      genes encoding mitochondrial proteins, the GC-rich, immediate 5'-flanking region
      of the DCI transcription initiation site lacks typical TATA and CAAT boxes;
      instead, two GC box consensus sequences are present. Introns 2 and 6 contain
      several Alu repetetive sequences. The human DCI gene locus was assigned to
      chromosome 16 by use of human-rodent somatic cell hybrids and to chromosome
      16p13.3 by chromosomal in situ suppression hybridization studies.

PMID- 7829075
TI  - Physical mapping of chromosome 17p13.3 in the region of a putative tumor
      suppressor gene important in medulloblastoma.
AB  - Deletion mapping of a medulloblastoma tumor panel revealed loss of distal
      chromosome 17p13.3 sequences in tumors from 14 of 32 patients (44%). Of the 14
      tumors showing loss of heterozygosity by restriction fragment length polymorphism
      analysis, 14 of 14 (100%) displayed loss of the telomeric marker p144-D6
      (D17S34), while a probe for the ABR gene on 17p13.3 was lost in 7 of 8 (88%)
      informative cases. Using pulsed-field gel electrophoresis, we localized the
      polymorphic marker (VNTR-A) of the ABR gene locus to within 220 kb of the p144-D6
      locus. A cosmid contig constructed in this region was used to demonstrate by
      fluorescence in situ hybridization that the ABR gene is oriented
      transcriptionally 5' to 3' toward the telomere. This report provides new physical
      mapping data for the ABR gene, which has not been previously shown to be deleted
      in medulloblastoma. These results provide further evidence for the existence of a
      second tumor suppressor gene distinct from p53 on distal chromosome 17p.

PMID- 7829076
TI  - A YAC contig spanning the nevoid basal cell carcinoma syndrome, Fanconi anaemia
      group C, and xeroderma pigmentosum group A loci on chromosome 9q.
AB  - Nevoid basal cell carcinoma syndrome (NBCCS, Gorlin syndrome) is an autosomal
      dominant disorder, characterized primarily by multiple basal cell carcinomas,
      epithelium-lined jaw cysts, and palmar and plantar pits, as well as various other
      features. Loss of heterozygosity studies and linkage analysis have mapped the
      NBCCS gene to chromosome 9q and suggested that it is a tumor suppressor. The
      apparent sensitivity of NBCCS patients to UV and X-irradiation raises the
      possibility of hypersensitivity to DNA-damaging reagents or defective DNA repair
      being etiological in the disorder. The recent mapping of the Fanconi anaemia
      group C (FACC) and xeroderma pigmentosum complementing group A (XPAC) genes to
      the same region on 9q has led us to begin the molecular dissection of the 9q22
      q31 region. PCR analysis of the presence or absence of 10 microsatellite markers
      and exons 3 and 4 of the XPAC and FACC genes, respectively, allowed us to order
      12 YACs into an overlapping contig and to order the markers as follows:
      D9S151/D9S12P1-D9S12P2-D9S197-D9S196-D9 S280-FACC-D9S287/XPAC-D9S180-D9S6-D9 S176
      . Sizing of the YACs has provided an initial estimate of the size of the NBCCS
      candidate region between D9S12 and D9S180 to be less than 1.65 Mb.

PMID- 7829077
TI  - Gray code masks for sequencing by hybridization.
AB  - In light-directed synthesis of high-density oligonucleotide arrays for sequencing
      by hybridization, synthesis errors result from the unintended illumination of
      chip regions that should remain dark. Most synthesis errors occur at the borders
      of illuminated regions, where light diffraction, internal reflection, and
      scattering produce the most unintended illumination. A combinatorial synthesis
      strategy based on two-dimensional Gray codes was devised to reduce the overall
      lengths of these borders in masks for photolithographic chip design. This article
      describes an application of two-dimensional Gray codes and demonstrates that
      masks based on this approach are optimal for minimizing the border length in
      VLSIPS (very large scale immobilized polymer synthesis).

PMID- 7829078
TI  - Mutation screening of the RYR1 gene in malignant hyperthermia: detection of a
      novel Tyr to Ser mutation in a pedigree with associated central cores.
AB  - The ryanodine receptor gene (RYR1) has been shown to be mutated in a small number
      of malignant hyperthermia (MH) pedigrees. Missense mutations in this gene have
      also been identified in two families with central core disease (CCD), a rare
      myopathy closely associated with MH. In an effort to identify other RYR1
      mutations responsible for MH and CCD, we used a SSCP approach to screen the RYR1
      gene for mutations in a family exhibiting susceptibility to MH (MHS) where some
      of the MHS individuals display core regions in their muscle. Sequence analysis of
      a unique aberrant SSCP has allowed us to identify a point mutation cosegregating
      with MHS in the described family. The mutation changes a conserved tyrosine
      residue at position 522 to a serine residue. This mutation is positioned
      relatively close to five of the six MHS/CCD mutations known to date and provides
      further evidence that MHS/CCD mutations may cluster in the amino terminal region
      of the RYR1 protein.

PMID- 7829079
TI  - Close linkage of the dominant cataract mutations (Cat-2) with Idh-1 and cryge on
      mouse chromosome 1.
AB  - The murine dominant gene Cat-2 was located on chromosome 1 between the loci of
      fuzzy and leaden. Subsequent linkage analysis revealed one recombinant between
      Cat-2t and isocitrate dehydrogenase-1, and one between Cat-2t and gamma E
      crystallin among 338 offspring in three-point backcrosses. The resulting genetic
      distance between the loci is 0.3 +/- 0.3 cM. The very close linkage between the
      Cat-2 and the gamma-crystallin gene cluster together with the finding of reduced
      gamma-crystallin transcripts in mutant lenses suggest strongly that the gamma
      crystallin genes may be candidate genes for the Cat-2 mutations.

PMID- 7829080
TI  - Assignment of the mouse homologues of 6 loci from HSA1p to chromosomes 3 and 4.
AB  - To increase the number of markers on distal mouse chromosome 4, knowledge of the
      synteny homology between this region and human chromosome 1p (HSA1p) was used to
      identify candidate homologous mouse genes. Ten probes corresponding to loci on
      human chromosome 1p were tested to reveal polymorphisms between C57BL/6 and DBA/2
      mice, the progenitors of the 26 BXD recombinant inbred strains. These strains
      were typed with six of these probes and typed for inheritance of mouse-specific
      microsatellite markers. Five mouse homologues of human genes were assigned to
      distal mouse chromosome 4 in the following order (including MIT microsatellites):
      (cen)-D4Mit71-Lap18-D4Mit69-C1qB-Plod/T nfr2-Cd30-(tel). Furthermore, an
      additional HSA1p marker, Cd53, mapped close to Amy1 on mouse chromosome 3, and a
      sequence related to Lap18 mapped to mouse chromosome 17, near D17Mit3. This
      comparative approach suggests that the human counterparts of these genes may have
      a similar order on human chromosome 1p and also indicates that Lap18, C1qB, and
      Nhe1 are candidates for a recently described diabetes susceptibility gene on
      mouse chromosome 4.

PMID- 7829081
TI  - Molecular cloning and characterization of the mouse medium-chain acyl-CoA
      dehydrogenase cDNA.
AB  - Medium-chain acyl-CoA dehydrogenase (MCAD) is one of the three straight-chain
      length-specific dehydrogenases involved in the first step of fatty acid
      oxidation. Inherited defects of acyl-CoA dehydrogenases occur in humans, and MCAD
      deficiency is the most common. We have cloned the coding and 3' untranslated
      sequence of mouse MCAD cDNA. The mouse MCAD cDNA coding region is 1263 bp long
      with a 3' untranslated region of 576 bp and encodes a 421 amino acid precursor
      protein. Comparing the nucleotide and deduced amino acid sequences of the mouse
      MCAD cDNA to rat and human MCAD cDNAs reveals considerable similarity between
      species. Amino acid residues where substitutions result in human MCAD deficiency
      are conserved in the mouse. Amino acid residues involved in important enzymatic
      functions are also conserved.

PMID- 7829082
TI  - A point mutation in the putative TATA box, detected in nondiseased individuals
      and patients with hereditary breast cancer, decreases promoter activity of the 17
      beta-hydroxysteroid dehydrogenase type 1 gene 2 (EDH17B2) in vitro.
AB  - EDH17B2, the gene encoding 17 beta-hydroxysteroid dehydrogenase type 1, has been
      suggested as a candidate for the familial breast cancer gene, BRCA1, located on
      17q12-q21. We analyzed the promoter region of EDH17B2 in DNA from 20 control
      individuals and 40 patients with familial breast cancer. Two frequent (designated
      vI and vIII) and two rare (vII and vIV) nucleotide variations were present in
      both the breast cancer patients and the controls, except the alteration vII,
      which was found only in one patient. Although the data do not support the
      identification of EDH17B2 as the BRCA1 gene, it is of interest that point
      mutation vIV (A-->C) was located in the putative TATA box of the EDH17B2 gene.
      Reporter gene analyses showed that the mutation vIV decreases EDH17B2 promoter
      activity by an average of 45% in in vitro assays, suggesting that nucleotide A at
      position -27 is significant for efficient transcription.

PMID- 7829083
TI  - Localization of the human genes encoding the two subunits of general
      transcription factor TFIIE.
AB  - TFIIE is a general transcription factor for class II genes composed of two types
      of subunits, a large one of 56 kDa and a small of 34 kDa. By Southern analysis at
      high and at low stringency of a panel of mouse/human hybrid cell lines and by in
      situ chromosomal hybridization, we have demonstrated that both polypeptides are
      encoded by genes that are single copy in the human genome and are localized at
      3q13-q21 and at 8p12, respectively. A TaqI RFLP (heterozygosity index of 0.07)
      was detected at the locus for the 56-kDa subunit.

PMID- 7829084
TI  - Genomic cloning of the mouse LDL receptor related protein/alpha 2-macroglobulin
      receptor gene.
AB  - The LDL receptor-related protein (LRP) or alpha 2-macroglobulin receptor (A2mr)
      is encoded by a 15-kb mRNA in mouse and human. Probes encompassing different
      regions of the mouse cDNA were used to isolate clones from a cosmid library of
      mouse strain 129. Four overlapping cosmids were used for restriction mapping and
      Southern blot analysis. This map and hybridization data obtained with
      oligonucleotide probes from the 5' and 3' ends of the Lrp cDNA demonstrated that
      the mouse gene is approximately 85 kb in size. The Lrp promoter region was
      sequenced and reveals strong evolutionary conservation of putative regulatory
      elements between mouse and human. The present study will facilitate detailed
      elucidation of the function of LRP in vivo.

PMID- 7829085
TI  - Allelic ladder characterization of the short tandem repeat polymorphism located
      in the 5' flanking region to the human coagulation factor XIII A subunit gene.
AB  - The short tandem repeat (STR) polymorphism present within the 5' untranslated
      region of the human coagulation factor XIII A subunit gene, HUMF13A01[AAAG]n, was
      evaluated using an allelic ladder, i.e., a standard size marker consisting of
      amplified alleles from the locus. The allelic ladder was constructed by pooling
      12 polymerase chain reaction (PCR)-amplified alleles identified by their
      differential migration in denaturing polyacrylamide gel electrophoresis. This
      standard marker was used to distinguish 14 different alleles observed at this
      locus. Sequence analyses indicate that 13 of the alleles contain 4 through 16
      iterations of the tandemly repeated AAAG sequence, respectively. The remaining
      allele carries four repeats and displays a deletion of two consecutive
      nucleotides (GT), one base distal to the repeat region. The allelic ladder was
      employed to type 326 F13A01 chromosomes rapidly and reliably in representatives
      of a German Caucasian population. Population data were analyzed with respect to
      Hardy-Weinberg Equilibrium (HWE) and compared with those of a previously studied
      Houston, Texas, Caucasian population.

PMID- 7829086
TI  - Localization of the 9p melanoma susceptibility locus (MLM) to a 2-cM region
      between D9S736 and D9S171.
AB  - A familial melanoma susceptibility locus (MLM) was identified on the short arm of
      chromosome 9 in a set of Utah and Texas kindreds. Subsequent confirmation was
      reported for a set of 26 Australian kindreds, a set of 7 Dutch kindreds, and a
      set of 13 NIH melanoma kindreds. The original localization report placed the
      locus near the IFNA-D9S126 interval on chromosome 9p. We report further
      localization using D9S171 and a newly developed marker, D9S736, both of which lie
      in the IFNA-D9S126 interval. Analysis of this set of kindreds places the melanoma
      susceptibility locus in a 2-cM region that is proximal to D9S736 and distal to
      D9S171.

PMID- 7829087
TI  - Mapping of the gene for the tyrosine kinase Itk to a region of conserved synteny
      between mouse chromosome 11 and human chromosome 5q.
AB  - The protein-tyrosine kinase gene Itk is expressed preferentially in T lymphoid
      cells of the mouse and is induced by IL-2. A related gene, Btk, is expressed in
      the murine B lymphoid and myeloid lineages. Because mutations in Btk and the
      corresponding human gene are associated with X-linked immunodeficiency syndromes,
      it was of interest to map Itk and its human counterpart. By Southern blot
      analysis of DNA from the progeny of two multilocus crosses, murine Itk was mapped
      to Chromosome 11. By fluorescence in situ hybridization, human ITK was mapped to
      5q32-q33. Murine Itk and its human homologue lie within regions of conserved
      synteny that include several growth factor and growth factor receptor genes. This
      region in humans is frequently deleted in the myelodysplastic syndrome,
      suggesting possible involvement of ITK in this disorder.

PMID- 7829088
TI  - Localization of the human beta-catenin gene (CTNNB1) to 3p21: a region implicated
      in tumor development.
AB  - The human beta-catenin locus (CTNNB1) was mapped by in situ fluorescence analysis
      to band p21 on the short arm of chromosome 3, a region frequently affected by
      somatic alterations in a variety of tumors. PCR primers for the genomic
      amplification of beta-catenin sequences were selected on the basis of homology to
      exon 4 of the Drosophila armadillo gene. Analysis of a panel of somatic cell
      hybrids confirmed the localization of beta-catenin on human chromosome 3.
      Furthermore, exclusion mapping of three hybrids carrying defined fragments of the
      short arm of human chromosome 3 allowed us to determine the position of the
      CTNNB1 locus close to the marker D3S2 in 3p21.

PMID- 7829089
TI  - Thermolabile phenol sulfotransferase gene (STM): localization to human chromosome
      16p11.2.
AB  - Thermolabile (TL) phenol sulfotransferase (PST) catalyzes the sulfate conjugation
      of phenolic monoamine neurotransmitters such as dopamine and serotonin. We
      recently cloned a cDNA for human liver TL PST and expressed it in COS-1 cells. We
      now report the chromosomal localization of the human TL PST gene (STM) as well as
      its partial sequence. DNA from NIGMS Human/Rodent Somatic Cell Hybrid Mapping
      Panels 1 and 2 was screened by use of the PCR, and the STM gene was mapped to
      chromosome 16. Regional localization to 16p11.2 was performed by PCR analysis of
      a high-resolution mouse/human somatic cell hybrid panel that contained defined
      portions of human chromosome 16.

PMID- 7829090
TI  - Cloning and chromosome localization of the mouse Ews gene.
AB  - The human EWS gene encodes a putative RNA binding protein. As a result of
      acquired chromosome rearrangement, the N-terminal portion of the EWS protein is
      fused to the DNA binding domain of either FLI-1 or ERG in the Ewing family of
      tumors and to the DNA binding domain of ATF1 in malignant melanoma of soft parts.
      We have determined the cDNA sequence of the mouse Ews gene. Its nucleotide
      sequence and its translation product demonstrate 93 and 98% homology with the
      human EWS cDNA and protein, respectively. The murine Ews locus lies within a
      conserved synteny segment between human chromosome 22q12 and mouse chromosome
      11A1-A3.

PMID- 7829091
TI  - Assignment of the human MAD and MXI1 genes to chromosomes 2p12-p13 and 10q24-q25.
AB  - MAD and MXI1, two recently described members of the basic helix-loop-helix (bHLH)
      gene family, encode proteins that dimerize with and modulate the DNA binding of
      max. In turn, mad-max or mxi1-max heterodimers or max homodimers can compete for
      DNA binding sites with dimers formed between max and myc oncoproteins and
      antagonize the transcriptional activities of this latter class of proteins. Using
      a combination of somatic cell mapping and fluorescence in situ hybridization
      techniques, we have determined the chromosomal locations of the MAD and MXI1
      genes. The MAD gene maps to chromosome 2p12-p13, a region involved in
      translocations and deletions in acute and chronic lymphocytic leukemias as well
      as non-lymphocytic leukemias and Hodgkin disease. The MXI1 gene localizes to
      chromosome 10q24-q25, a region involved in translocations and deletions in acute
      and chronic lymphocytic leukemias and prostatic carcinomas. The availability of
      genomic clones of MAD and MXI1 will permit an assessment of their involvement in
      these diseases at the molecular level.

PMID- 7829092
TI  - Assignment of human xanthine dehydrogenase gene to chromosome 2p22.
AB  - Xanthine dehydrogenase (XDH, EC 1.1.1.204) oxidizes a variety of purines,
      pterins, and other heterogenic nitrogen compounds, serving as a rate-limiting
      enzyme in nucleic acid degradation. The genetic defect of XDH results in
      hereditary xanthinuria and other disorders in purine metabolism. Based on the
      cloning and sequencing results of human XDH cDNA in our laboratory, we studied
      the localization and sublocalization of the XDH gene. A Version 3.0 human-hamster
      somatic cell hybrid PCRable DNA panel and specific PCR primers derived from human
      XDH cDNA for amplification were used to assign the XDH gene to human chromosome
      2. The fidelity of the PCR product was confirmed by nucleotide sequencing the PCR
      product. The assignment of the XDH gene to chromosome 2 at band p22 was
      established by fluorescence in situ hybridization on human metaphase chromosomes
      using a clone from a pWE 15 cosmid library containing the XDH gene. The results
      should be useful for further studies of the molecular basis for hereditary
      xanthinuria and other genetic disorders related to abnormal XDH activity.

PMID- 7829093
TI  - An in-frame trinucleotide repeat in the coding region of the human cellular
      glutathione peroxidase (GPX1) gene: in vivo polymorphism and in vitro
      instability.
AB  - We report the variation in vivo and instability in vitro of an in-frame GCG
      trinucleotide repeat in the human cellular glutathione peroxidase (GPX1) gene. In
      a population study of 110 alleles from 55 unrelated individuals, the allele
      frequencies for 4, 5, and 6 GCG repeats were 0.40, 0.35, and 0.25, respectively.
      No allele was associated with diminished enzyme activity. Current stocks of HL-60
      cells, a human myeloid leukemia cell line, are homozygous for the 6-repeat
      allele. Early passage HL-60 cells frozen in 1976 show a 4/6 genotype and
      "intermediate" passage cells frozen in 1985 contain both 4/6 and 5/6 genotypes.
      Thus, the expansion of the repeat appears to have developed in the course of
      multiple passages of the rapidly proliferating cell line.

PMID- 7829094
TI  - Confirmation of the assignment of the gene encoding Kv1.3, a voltage-gated
      potassium channel (KCNA3) to the proximal short arm of human chromosome 1.

PMID- 7829095
TI  - Mapping of the gene for high-density lipoprotein binding protein (Hdlbp) to
      proximal mouse chromosome 1.

PMID- 7829096
TI  - Human 60-kDa SS-A/Ro ribonucleoprotein autoantigen gene (SSA2) localized to 1q31
      by fluorescence in situ hybridization.

PMID- 7829097
TI  - Genomic organization of the human VP16 accessory protein, a housekeeping gene
      (HCFC1) mapping to Xq28.
AB  - The region between DXS52 and Factor VIII gene in the human Xq28 chromosomal band
      contains a G+C-rich isochore to which many genes have been mapped. We report here
      the isolation and characterization of a transcript mapping about 50 kb telomeric
      from the vasopressin type 2 receptor gene in a 180-kb YACs/cosmid contig
      containing the L1CAM gene at its centromeric end. The determined transcribed
      sequence from a human fetal brain library is identical to that of the recently
      identified accessory protein HCFC1 (host cell factor, also called C1) that
      activates herpes simplex virus VP16 (alpha TIF) transactivator protein for
      association with the octamer motif-binding protein Oct-1 (Cell 74: 115, 1993).
      The gene is expressed in a ubiquitous pattern and a larger transcript of
      approximately 10 kb is present in all the tissues tested, while an alternatively
      spliced RNA of approximately 8.0 kb is present in muscle and heart tissues.
      Genomic sequencing allowed us to determine that the sequenced transcript is
      assembled from 26 exons spread over a relatively small genomic region of
      approximately 24 kb. This alllowed us to determine that a previously reported
      cDNA clone arises from the splicing out of an internal portion of exon 8 which
      does not change the reading frame. All together these results raise the
      possibility that alternative mRNA processing could partly contribute to the
      diversity of the polypeptide HCFC1 family in a subset of tissues.

PMID- 7829098
TI  - Identification of a mouse homologue of the Saccharomyces cerevisiae recombination
      and repair gene, RAD52.

PMID- 7829099
TI  - The gene for membrane protein E16 (D16S469E) maps to human chromosome 16q24.3 and
      is expressed in human brain, thymus, and retina.

PMID- 7829100
TI  - Structure and polymorphism of the mouse myelin/oligodendrocyte glycoprotein gene.
AB  - We have isolated and characterized genomic clones containing the mouse
      myelin/oligodendrocyte glycoprotein (MOG) gene. It spans a region of 12.5 kb and
      consists of eight exons. Its exon-intron structure differs from that of classical
      MHC-class I genes, with which it is linked in the mouse genome. Nucleotide
      sequencing of the 5' flanking region reveals that it contains several putative
      protein-binding sites, some of them in common with other myelin gene promoters.
      One intragenic polymorphism has been identified: it consists of a GA repeat,
      defining at least three alleles in mouse inbred strains, and is easily detectable
      using the polymerase chain reaction method.

PMID- 7829101
TI  - Isolation of novel and known genes from a human fetal cochlear cDNA library using
      subtractive hybridization and differential screening.
AB  - We used a combination of subtractive hybridization and differential screening
      strategies to identify genes that may function normally in hearing and, when
      mutated, result in deafness. A human fetal cochlear (membranous labyrinth) cDNA
      library was subtracted against total human fetal brain RNAs by an avidin-biotin
      based procedure to enrich for cochlear transcripts. Subtracted cochlear clones
      were differentially screened with 32P-labeled total cochlear and total brain cDNA
      probes. Sequence analysis of clones that hybridized more intensely with cochlear
      than with brain cDNA probes revealed some previously characterized genes,
      including mitochondrial sequences, collagen type I alpha-2 (COL1A2), collagen
      type II alpha-1 (COL2A1), collagen type III alpha-1 (COL3A1), spermidine/spermine
      N1-acetyltransferase (SAT), osteonectin (SPARC), and peripheral myelin protein 22
      (PMP22). Also identified were clones that are potential novel cochlear genes.
      Northern blots of cochlear and brain RNAs probed with COL1A2, COL2A1, COL3A1,
      SAT, SPARC, PMP22, and a novel sequence, designated Coch-5B2, confirm results of
      the subtractive procedure by showing preferential cochlear expression. A number
      of these genes serve structural or regulatory functions in extracellular matrix
      or neural conduction; defects in some of these genes are associated with
      disorders involving hearing loss. Partial sequence analysis of Coch-5B2 reveals a
      von Willebrand factor type A-like domain in this cDNA. To assess the cochlear
      specificity of Coch-5B2, a Northern blot panel of 14 human fetal tissue RNAs was
      probed with Coch-5B2, showing differential expression of this novel gene in the
      cochlea.

PMID- 7829102
TI  - Haplotype mapping and sequence analysis of the mouse Nramp gene predict
      susceptibility to infection with intracellular parasites.
AB  - The mouse chromosome 1 locus Bcg (Ity, Lsh) controls the capacity of the tissue
      macrophage to restrict the replication of antigenically unrelated intracellular
      parasites and therefore determines the natural resistance (BCG-R, dominant) or
      susceptibility (BCG-S, recessive) of inbred mouse strains to infection with
      diverse pathogens, including several Mycobacterium species, Salmonella
      typhimurium, and Leishmania donovani. We have used a positional cloning strategy
      based on genetic and physical mapping, YAC cloning, and exon trapping to isolate
      a candidate gene for Bcg (Nramp) that encodes a predicted macrophage-specific
      transport protein. We have analyzed a total of 27 inbred mouse strains of BCG-R
      and BCG-S phenotypes for the presence of nucleotide sequence variations within
      the coding portion of Nramp and have carried out haplotype typing of the
      corresponding chromosome 1 region in these mice, using 11 additional polymorphic
      markers mapping in the immediate vicinity of Nramp. cDNA cloning and nucleotide
      sequencing identified 5 nucleotide sequence variations within Nramp in the inbred
      strains; while 4 of these represented silent sequence polymorphisms, one G to A
      substitution at nucleotide position 783 resulted in the non-conservative
      replacement of Gly105 to Asp105 within the second predicted transmembrane domain
      (TM2) of the Nramp protein. An absolute association of this allelic variation and
      Bcg phenotype was observed in the 20 BCG-R strains (Gly105) and 7 BCG-S strains
      (Asp105) tested. Moreover, sequence analysis of the corresponding region of the
      Nramp gene from distantly related species indicated strong amino acid sequence
      conservation of TM2, including an invariant glycine at position 105. Haplotype
      mapping using sequence polymorphism identified within Nramp and additional RFLPs
      and SSLPs from the region revealed that although the 20 BCG-R strains analyzed
      showed diverse allelic combinations for these markers, the 7 BCG-S strains tested
      share a conserved core haplotype of 2.2 Mb overlapping and including Nramp. Taken
      together, these results suggest that (1) Gly105 is the wildtype form of Nramp and
      that the nonconservative substitution to Asp105 underlies the BCG-S phenotype,
      and (2) Bcg8 alleles carry the same Gly105-->Asp105 mutation and are identical by
      descent.

PMID- 7829103
TI  - Comparative mapping of canine and human proximal Xq and genetic analysis of
      canine X-linked severe combined immunodeficiency.
AB  - Parallel genetic analysis of animal and human genetic diseases can facilitate the
      identification and characterization of the causative gene defects. For example,
      canine X-linked severe combined immunodeficiency (SCID) is characterized by
      clinical, pathological, and immunological manifestations similar to the most
      common form of human SCID. To derive a canine syntenic map including genes that
      in humans are located in proximal Xq, near human X-linked SCID, poly(TG)
      polymorphisms were identified at the canine phosphoglycerate kinase (PGK) and
      choroideremia (CHM) loci. These plus a polymorphic poly(CAG) sequence in exon 1
      of the canine androgen receptor gene (AR) were used to genotype members of the
      colony informative for X-linked SCID. No recombinations among SCIDX1, AR, PGK, or
      CHM were observed. Fluorescence in situ hybridization localized PGK and CHM to
      proximal Xq in the dog, in the same chromosomal location occupied by the human
      genes. Somatic cell hybrid analysis and methylation differences at AR
      demonstrated that female dogs carrying X-linked SCID have the same lymphocyte
      limited skewed X-chromosome inactivation patterns as human carriers. These
      genetic and phenotypic findings provide evidence that mutations in the same gene,
      now identified as the gamma chain of the IL-2 receptor, cause canine and human X
      linked SCID. This approach is an efficient method for comparative gene mapping
      and disease identification.

PMID- 7829104
TI  - IL-2R gamma gene microdeletion demonstrates that canine X-linked severe combined
      immunodeficiency is a homologue of the human disease.
AB  - X-linked severe combined immunodeficiency (SCID) is characterized by profound
      defects in cellular and humoral immunity and, in humans, is associated with
      mutations in the gene for the gamma chain of the IL-2 receptor (IL-2R gamma). We
      have examined this gene in a colony of dogs established from a single X-linked
      SCID carrier female. Affected dogs have a 4-bp deletion in the first exon of the
      IL-2R gamma gene, which precludes the production of a functional protein,
      demonstrating that the canine disease is a true homologue of human X-linked SCID.

PMID- 7829105
TI  - Isolation and mapping of human chromosome 21 cDNA: progress in constructing a
      chromosome 21 expression map.
AB  - We have isolated 175 cDNA clones from a fetal brain library by direct cDNA
      selection using genomic DNA isolated from pools of human chromosome 21 (HC21)
      cosmids. DNA sequences have revealed that 16 of these cDNA clones contain
      overlapping sequences. Of the other 159 cDNA sequences, 10 match previously
      identified HC21 genes, and 9 match previously determined cDNA sequences,
      including the Wilms tumor related transcript (QM), the human testican cDNA, the
      mammalian calponin cDNA, and 6 anonymous expressed sequence tags. All isolated
      cDNAs were hybridized to their corresponding cosmids, which suggests that they
      originated from HC21. We have localized 92 cDNA clones to previously reported
      HC21q YACs. The remaining unmapped cDNAs contain either sequences not included in
      the isolated HC21q YACs or sequences that hybridize to yeast DNA. The cDNAs not
      included in the YACs should be useful in isolating new YACs to bridge the gaps.
      PCR primers were derived from 4 novel cDNA sequences that had been mapped to the
      YACs in the suspected Down syndrome region and used in RT-PCR analysis. All 4
      primer sequences amplified RNA fragments with the expected sizes, suggesting that
      these sequences could be used for expression analysis. The construction of a
      chromosome 21 cDNA map not only is important in the refinement of physical maps,
      but also will identify a set of genes in the disease regions for detailed
      characterization.

PMID- 7829106
TI  - Cloning, sequencing, and mapping of the human chromosome 14 heat shock protein
      gene (HSPA2).
AB  - A genomic clone for the human heat shock protein (HSP) 70 gene located on
      chromosome 14 was isolated and sequenced. The gene, designated HSPA2, has a
      single open reading frame of 1917 bp that encodes a 639-amino acid protein with a
      predicted molecular weight of 70,030 Da. Analysis of the sequence indicates that
      HSPA2 is the human homologue of the murine Hsp70-2 gene with 91.7% identity in
      the nucleotide coding sequence and 98.2% in the corresponding amino acid
      sequence. HSPA2 has less amino acid homology to other members of the human HSP70
      gene family, 83.3% to the heat-inducible HSP70-1 gene and 86.1% with the human
      heat shock cognate gene HSC70. HSPA2 is constitutively expressed in most tissues,
      with very high levels in testis and skeletal muscle. Significant but lower levels
      are also expressed in ovary, small intestine, colon, brain, placenta, and kidney.
      A yeast artificial chromosome (YAC) clone containing HSPA2 (YAC741H4) that also
      contained the polymorphic marker D14S63 was identified. This 670-kb YAC was
      mapped to 14q24.1 by fluorescence in situ hybridization (FISH). Subsequent two
      color FISH and genetic mapping placed HSPA2/D14S63 proximal to the markers D14S57
      and D14S77.

PMID- 7829107
TI  - Molecular cloning of cDNAs encoding human carnitine acetyltransferase and mapping
      of the corresponding gene to chromosome 9q34.1.
AB  - Using a combination of PCR screening of cDNA libraries and reverse transcription
      PCR, we have cloned three overlapping DNA fragments that encode human carnitine
      acetyltransferase (CAT), a key enzyme for metabolic pathways involved with the
      control of the acyl-CoA/CoA ratio in mitochondria, peroxisomes, and endoplasmic
      reticulum. The resulting cDNA (2436 bp) hybridizes to a mRNA species of
      approximately 2.9 kb that is particularly abundant in skeletal muscle and encodes
      a 68-kDa protein containing a peroxisomal targeting signal. The sequence matches
      those of several tryptic peptides obtained from purified human liver CAT and
      shows striking similarities with other members of the carnitine/choline
      acetyltransferase family very distant throughout evolution. CAT cDNA has also
      been used for fluorescence in situ hybridization on metaphase spreads of human
      chromosomes, and the corresponding gene, CAT1, has been mapped to chromosome
      9q34.1.

PMID- 7829108
TI  - Peer review: when enough is enough.

PMID- 7829109
TI  - A typology of nursing therapeutics.
AB  - A typology of nursing therapeutics is proposed in relation to the intended level
      of alteration of patient responses, patterns, or life processes. Nursing
      therapeutics is described as single or multiple interventions by the nurse to
      alter life processes, life patterns, and functional health patterns.

PMID- 7829110
TI  - Exercise guidelines for pregnant women.
AB  - Despite remarkable improvements in high technologies and an increase in the
      number of studies related to exercise for pregnant women, the guidelines for
      maternal exercise remain contradictory. The effects of exercise in pregnant women
      and cardiovascular modifications due to pregnancy, and effects of maternal
      exercise on the fetal environment, including uterine and umbilical hemodynamic
      changes, are reviewed. Suggested future directions in this area of nursing
      science are discussed.

PMID- 7829111
TI  - A model for symptom management. The University of California, San Francisco
      School of Nursing Symptom Management Faculty Group.
AB  - Symptom management is a challenging experience for patients, families and health
      care professionals. A model for symptom management applicable to symptoms and
      patient populations in a variety of settings was developed by the Center for
      Symptom Management faculty of the University of California, San Francisco. The
      model, focusing on symptom experience, management strategies, and outcomes, was
      derived from faculty research and practice. The model is applicable to practice
      and research, and is currently being used in a variety of studies and settings.

PMID- 7829112
TI  - HIV infection, exercise, and immune function.
AB  - Decreased physical endurance is viewed by both HIV-infected people and their
      primary nurses as a major healthcare problem. There is a widespread belief among
      HIV-infected people that the way to improve their endurance is through exercise.
      Yet healthcare providers are divided about the role of exercise. This paper
      presents an overview of decreased endurance as a major problem in this
      population, with a review of the literature on exercise in healthy and
      chronically-ill populations, including those with HIV infection, and its effect
      on immune function.

PMID- 7829113
TI  - Decision points in choosing family self-report scales in research.
AB  - Literature that systematically highlights critical decision-making points in
      conducting family research is sparse. The wide-spread use of self-report
      instruments in family research suggests that explication of decision-making
      points involved in the use of self-report instruments is needed. A specific
      instrument, the Family Environment Scale (Moos & Moos, 1986), is used to
      illustrate relevant decision-making. Conceptualization of a study,
      instrumentation, and data analysis are addressed.

PMID- 7829114
TI  - Theoretical considerations for research on environmental stress and health.
AB  - Research on hospital noise may have implications for the usefulness of stress
      theory as a framework for the study of environmental stress and stress-related
      health outcomes. In this article, the results of hospital noise research are
      described. It is argued that noise-induced stress in hospitals is largely
      uncontrollable by individual coping and that stress theory may therefore need to
      be supplemented for the reduction of reactivity. Three concepts are proposed for
      this purpose. Primary among these is an intervention concept--enhancement of
      person-environment compatibility. Others are ongoing societal and technological
      development, and intrinsic sensitivity to specific stressors in the environment.
      Future research should attempt to reveal whether these concepts are consistently
      effective in the management of hospital noise and other environmental stressors.

PMID- 7829115
TI  - Delirium and physical restraint in the hospitalized elderly.
AB  - Delirium or acute confusion increase the likelihood of physical restraint use and
      subsequent harmful physical and psychological effects. Assessment for delirium is
      presented as a conceptual framework to guide researchers, administrators, and
      clinicians in developing strategies to decrease the use of physical restraint and
      to support quality of life for hospitalized older adults.

PMID- 7829116
TI  - The Fulbright Scholar Program.

PMID- 7829117
TI  - Promoting situational support for nurses in practice.
AB  - Situational support entails promoting autonomy, control over practice, group
      cohesion, manager consideration, and substantive exchange. Support can reinforce
      nurses' coping mechanisms, preserve their integrity, and thereby promote quality
      patient care. Using concept clarification and case examples the authors identify
      support mechanisms and coping styles for nurses at work and discuss how
      situational support can be used to cope with stress.

PMID- 7829118
TI  - Conceptual analysis of rights using a philosophic inquiry approach.
AB  - A philosophic approach to analysis reveals that the concept of right(s), with 10
      identified attributes, is subject to ambiguous and inconsistent interpretation.
      This lack of clarity in interpretation contributes to controversy when rights are
      used for resolution of ethical conflict. Characteristics of rights contributing
      to their misinterpretation include their origins and the diverse ranges of their
      intended scope. Rights may be self-evident or derived from a contract. Although
      they are inalienable, they may not be operational. Furthermore, having a right
      does not entail having the power to attain it. This philosophic analysis yields a
      theoretic definition intended to guide nurses in rational interpretation and use
      of rights in their practices.

PMID- 7829119
TI  - Rethinking the merger of the clinical nurse specialist and the nurse practitioner
      roles.
AB  - The clinical nurse specialist (CNS) and nurse practitioner (NP) have been
      distinct and separate advanced nursing practice roles since the 1960s. The forces
      of economics and health care reform have fostered an interest in merging these
      two advanced practice roles. Economic and regulatory advantages have been noted
      in the literature for both roles. What is not so evident are the possible
      disadvantages. Several aspects of the merger issue are explored as is the recent
      background of the creation of the CNS and NP roles. Problems and questions are
      asked to stimulate future discussions in nursing's professional associations and
      in education and service settings.

PMID- 7829120
TI  - Successful aging of oldest old women in the Northeast Kingdom of Vermont.
AB  - Health lifeways of six oldest old women, who have lived in northeastern Vermont
      for an average of 70 years are described. Life histories were obtained using
      participant observation and intensive interviewing to identify dominant themes
      associated with successful aging: being a woman with family and friends, living
      off the land, dealing with difficult times, and working hard and staying active.
      Health values and practices as well as personal characteristics combined with a
      strong network of social support emerge as dimensions of successful aging and
      considerations for nursing practice.

PMID- 7829121
TI  - A study of symptom distress, health locus of control, and coping resources of
      aging post-polio survivors.
AB  - Nearly one-half of the estimated 1.63 million American patients who survived the
      polio epidemics of the 1940s and 1950s are re-experiencing symptoms of the acute
      illness. This exploratory study of 125 aging post-polio survivors examined the
      differences of symptom distress, health locus of control, and coping resources
      for survivors who had and those who had not incurred a chronic physical
      disability following the acute phase of poliomyelitis. The Symptom Rating Test,
      the Multidimensional Health Locus of Control Scale, and the Coping Resources
      Inventory were used. No significant differences were found between disability
      groups concerning symptom distress, health locus of control, or coping resources.
      However, significant negative correlations were found between coping resources
      and both the quantity and severity of symptom distress. The differences found
      between perceived health locus of control and both coping resources and symptom
      distress were marginally significant.

PMID- 7829122
TI  - Establishment of rat glutamic acid decarboxylase (GAD)-reactive T-cell clones
      from NOD mice.

PMID- 7829123
TI  - Dextran sulphate induces a PKC and actin independent internalisation of CD4.
AB  - Internalisation of CD4 is a well-known phenomenon. It occurs in the presence of
      phorbol myristate acetate (PMA), TPA or gangliosides and is usually completed
      within 30 min. Here, we describe an internalisation of CD4 molecules induced by
      low concentrations of high molecular weight dextran sulfate (M(r) 500 kDa) which
      differs from the classical mode in several ways. Internalisation is demonstrated
      by flow cytometry after simultaneous and consecutive staining of extracellular
      and internalised CD4 molecules and by visualisation by electron micrographs. A
      simple blockage of antibody binding sites on the CD4 molecule (epitope masking)
      by DS500, as widely believed, is definitely not responsible for the observed
      effects. DS500-mediated internalisation is a slow and energy-dependent process,
      where CD4 but not CD 2, 3, 8, 16, 56 and HLA-DR molecules are involved. The
      reaction reveals a characteristic time and concentration dependency. It does not
      require activation of protein kinase C (PKC) and cannot be inhibited by
      cytochalasin D. These results provide some more insight in the behavior of CD4 on
      lymphoid cell surfaces in response to high molecular weight polyanions such as
      dextran sulfate.

PMID- 7829124
TI  - Tubocurarin induces the wide spectrum of cytolytic effects in tumor cells.
AB  - Tubocurarin was shown to mediate a wide spectrum of cytolytic processes in tumor
      cells while peritoneal murine macrophages were resistant to its action. Group I
      of these processes was due to rapid (within 1-3 h) and nonspecific lysis mediated
      by relatively high (> 10(-5) M) concentrations of tubocurarin. Membrane damage
      with subsequent osmotic lysis was associated with these events. Processes of
      groups II and III were highly specific, cytolysis of group II having developed
      within 4-5 h and characterized by saturation at 5 x 10(-7) M. It was proposed
      that two types of necrosis contributed to the processes of group II. These
      pathways were induced by different concentrations of tubocurarin and also
      differed in their sensitivity to lysosomal inhibitor NH4Cl. Cytolysis of group
      III was associated with apoptosis and developed within 8-24 h. The significant
      acceleration of DNA fragmentation and subsequent cell death was achieved by
      increase of tubocurarin concentration from 5 x 10(-8) to 10(-6) M.

PMID- 7829125
TI  - Expression of aminopeptidase N/CD13 in tumour-infiltrating lymphocytes from human
      renal cell carcinoma.
AB  - We have previously demonstrated the expression of aminopeptidase N (APN, CD13) on
      synovial T cells from patients with different forms of arthritis. T cells of
      peripheral blood and serous body fluids are CD13-negative but can be stimulated
      to express CD13 after activation, e.g., with Con A. In the present report, double
      labelling and flow cytometry analyses were performed to characterize the
      phenotype of tumour-infiltrating lymphocytes (TIL). A large panel of antibodies
      specific for different activation-associated molecules on T cells was used. In
      contrast to TIL of lung cancer, TIL of renal cell carcinoma (RCC) consisted of
      significantly higher percentages of T cells expressing CD13, dipeptidylpeptidase
      N (DPIV, CD26) and HLA-DR, whereas T cells of lung cancer expressed more CD25,
      CD69 and CD54/ICAM1. No differences could be found in the expression of CD45RO,
      CD49a/VLA-1 and CD62L/L-selectin. Our results demonstrate that T cells in RCC and
      lung cancer differ in their phenotype, especially with respect to surface
      aminopeptidases. Investigations into the function of APN on T cells could be of
      help in gaining deeper insight into tumour defence as well as into general
      mechanisms of T cell functions.

PMID- 7829126
TI  - Induction of beta 2 integrin expression on an eosinophilic cell line (EoL-1) by
      the supernatant of mononuclear cells stimulated with specific allergen from
      asthmatic patients.
AB  - Adhesion molecules recently have been considered to play an important role in
      inflammatory processes in bronchial asthma. Our previous study revealed high
      expression of beta 2-integrin family (CR3, LFA-1 alpha, CD18) on hypodense
      eosinophils. Thus, from the point of view of cell-to-cell interaction between
      mononuclear cells and eosinophils, we examined whether the supernatant of
      mononuclear cells obtained from mite-allergic asthmatic patients cultured with
      specific allergen mite-allergen is involved in adhesion molecule expression using
      an eosinophilic cell line (EoL-1). These characteristics of beta 2-integrin
      family expression (high expression of beta 2 integrin) were induced by the
      supernatant of mononuclear cells from mite-allergic asthmatic patients stimulated
      with mite-allergen as well as with a combination of the recombinant
      eosinophilopoietic growth cytokines (IL-3, GM-CSF and IL-5). Thus, we could
      conclude that some cytokines produced by specific allergen stimulated mononuclear
      cells in asthmatics might be involved in allergic inflammation through the
      induction of adhesion molecule expression on eosinophils in asthma or allergic
      disorders.

PMID- 7829127
TI  - Macrophage-colony stimulating factor (M-CSF) stimulation induces cell death in
      HIV-infected human monocytes.
AB  - We show here that HIV-infected monocyte-macrophages stimulated by macrophage
      colony stimulating factor (M-CSF) undergo massive syncytia formation and die. The
      M-CSF-stimulated HIV-infected monocyte-macrophages (M/M) destroy themselves by
      blebbing out particles (resembling apoptotic bodies) which may contain condensed
      and marginated chromatin. The death of monocyte-macrophages is also characterized
      by the expression of "Tissue" Transglutaminase (tTG) which is one of the genes
      specifically expressed and activated in apoptising cells. Noteworthy, when the
      syncytia formation and consequently death is prevented, infected monocyte
      macrophages remain viable and produce large amounts of virus for an extended
      period. The concentrations of M-CSF (1000 U/ml) used in this work are similar to
      those that stimulate macrophages in vivo. This suggests that HIV killing of M/M
      in the presence of M-CSF could lead, in vivo, to a greater than expected loss of
      immune cells and may contribute to explain the complex derangement of the immune
      function observed in HIV-infected patients.

PMID- 7829128
TI  - Calcium signalling in individual T-cells measured by confocal microscopy.
AB  - Laser-scanning confocal microscopy was used in conjunction with a highly
      fluorescent Ca2+ indicator fluo-3 to visualize real-time alterations in the
      intracellular Ca2+ concentration ([Ca2+]i) in individual living Jurkat T-cells
      during the first minutes of activation by phytohaemagglutinin (PHA) at the
      physiological temperature (37 degrees C). With a delay of 30-120 s, PHA induced a
      strong [Ca2+]i peak in the micromolar range (1-3 microM). The rise in [Ca2+]i
      lasted for 1-2 minutes, and was followed by a sustained plateau of elevated
      [Ca2+]i in the 0.2-0.5 microM range. Some cells (10-20%) responded with
      additional asynchronous 0.5-1.5 microM peaks during the plateau phase. These
      oscillations continued for 10-20 minutes. The spans of the peaks ranged from 30
      to 100 s, intervals between peaks varied from 60 to 300 s. It was shown that the
      initial [Ca2+]i peak was associated with Ca2+ mobilisation from internal sources,
      whereas the plateau was maintained by an influx of Ca2+ from external medium. In
      K(+)-rich medium or in the presence of quinine, a K+ channel blocker, no
      secondary response to PHA-activation characterised by an elevated plateau was
      observed. The data suggest that the Ca2+ influx was dependent on the membrane
      potential and/or the extracellular K(+)-concentration. Optical sectioning showed
      that the intracellular Ca2+ distributed almost homogeneously throughout the cell
      volume both in control and in PHA-stimulated cells including those exhibiting
      Ca2+ oscillations. This suggests that Ca2+ signals are localized not only in
      cytoplasm at the cell plasma membrane but can be also transferred directly into
      the nucleus.

PMID- 7829129
TI  - Moabs MAS516 and 5B5, two fibroblast markers, recognize human follicular
      dendritic cells.
AB  - Follicular dendritic cells (FDC) are only located within follicles of secondary
      lymphoid tissues. The origin of this peculiar cell type is not clearly defined.
      To contribute to this study, we applied two monoclonal antibodies (MAS516 and
      5B5) considered as specific for fibroblasts to tonsil cryosections and to
      isolated follicular dendritic cells. On the basis of an enzyme cocktail digestion
      of human tonsils and a fractionation procedure on albumin gradients, FDC can be
      prepared in the form of cell aggregates with associated lymphoid cells. MAS516
      reacts with surface membrane molecules expressed by human fibroblasts, tissue
      macrophages and peripheral blood monocytes. With immunoperoxidase assays on
      tonsil cryosections connective tissue cells and macrophages are stained. Inside
      germinal centres, heavy labelling of the light zone was found. The MAS516
      staining pattern is very similar to that of specific FDC markers DRC-1 or BU10.
      All isolated FDC reacted with MAS516 antibody. 5B5, considered as a typical
      fibroblast marker, reacts with human prolyl-4-hydroxylase which is an
      intracellular enzyme related to collagen biosynthesis. In cryosections,
      interfollicular and capsular areas showed 5B5 positive connective tissue
      fibroblasts. In germinal centres, some cells presenting features of FDC were 5B5
      positive. After cell separation, 25%-50% of the isolated FDC were labelled with
      this antibody. This positivity of some FDC for 5B5 antibody may support the idea
      of their fibroblastic origin. The combination of observations realized in situ
      and after cell purification ensured an unequivocal recognition and identification
      of FDC.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7829130
TI  - Analysis of peripheral blood normal and malignant cells with the novel murine
      monoclonal antibody UN2.
AB  - The monoclonal antibody (mAb) UN2 was generated upon immunization of a Balb/c
      mouse with human thymocytes. mAb UN2 recognized an antigen expressed by a
      subpopulation of human thymocytes and peripheral blood lymphocytes. In thymus,
      mAb UN2 recognized cortical cells; its expression was higher on CD3bright than on
      CD3dim thymocytes. This antigen was also detected on peripheral blood
      granulocytes, monocytes, platelets and on cell lines MOLT4, U937 and KG1. mAb UN2
      was submitted to the 5th International Workshop and Conference on Human Leukocyte
      Differentiation Antigens, Boston, MA, 1993, and was assigned to the CD31.
      Expression of the UN2-recognized antigen in malignant lymphoid cells from 57
      cases of B-cell chronic lymphoproliferative disease and 4 of B-cell acute
      lymphoblastic leukemia was analysed in flow cytometry. Among the 57 cases of B
      cell chronic lymphoproliferative malignancies studied, 49 were classified as B
      cell chronic lymphocytic leukemia. These showed high (86 +/- 8%) UN2 antigen
      expression. In 8 cases of hairy-cell leukemia the percentage of cells reacting
      with mAb UN2 was 42 +/- 4%; the fluorescence intensity of labelled cells was
      lower than that displayed by cells of B-cell chronic lymphocytic leukemia and
      comparable to that of normal lymphoid cells. mAb UN2 could prove useful in
      analysis of the lymphoid development and diagnostics of B-cell chronic
      lymphoproliferative disorders.

PMID- 7829131
TI  - Overrepresentation of the V kappa IV subgroup in light chain deposition disease.
AB  - The variability subgroup of human monoclonal kappa chains purified from urine in
      3 consecutive patients with myeloma associated light chain deposition disease was
      determined from amino acid sequences of their first framework regions (FR1). N
      glycosylation was searched for by N-glycosidase F treatment. These data together
      with our previously published results, indicate the pathogenic potential of the
      rare V kappa IV subgroup and confirm the absence of detectable serum and urine
      free monoclonal light chains when they are N-glycosylated.

PMID- 7829132
TI  - Binding of serum autoantibodies to sialidase-treated tracheal epithelial cells.
      Determination of autoantibodies isotypes in normal and influenza virus infected
      guinea pig sera.
AB  - Cultured epithelial cells isolated from guinea pig trachea were treated with
      Vibrio cholerae sialidase. The treatment was not cytotoxic and resulted in
      membrane desialylation as assessed by measurement of sialic acids released, along
      with an increased fixation of the galactose-specific lectin peanut agglutinin.
      After incubation in serum from normal guinea pigs, membrane-bound immunoglobulins
      were detected using peroxidase-labelled antibodies. Sialidase-treated cells bound
      significantly more IgM than controls (P < 0.0005), whereas binding of IgG was not
      significantly different between treated and untreated cells (0.1 < P < 0.375);
      IgA were never detected. In influenza-infected guinea-pigs, as assessed by
      reactivity with peanut agglutinin, the tracheal and lung epithelium, as well as
      alveolar cells were hyposialylated. In these animals, the level of serum IgG
      autoantibodies capable to bind sialidase treated cultured cells increased, while
      the level of IgM autoantibodies did not change. These autoantibodies may
      participate in cellular dysfunctions and modified bronchoreactivity that occur
      during infection of the respiratory tract by sialidase-producing microorganisms,
      either through activation of the complement system, or subsequently to their
      reaction with cells expressing membrane complement and/or Fc receptors.

PMID- 7829133
TI  - Identification of a mannose-acetate-specific 87-kDa receptor responsible for
      human NK and LAK activity.
AB  - Target cell recognition and cytotoxicity of human CD56+ NK and LAK cells is
      readily inhibited by acetylated mannose. Two respective NK cell receptor
      candidates were isolated from human leukocyte lysates by mannose acetate affinity
      chromatography. The 87-kDa receptor showed sequence homologies with lactoferrin
      and the 59-kDa receptor represented a complex of two Ca-binding proteins MRP-8
      and MRP-14 reportedly expressed only by cells of myeloid origin. The 87-kDa
      receptor exhibited heterogeneity in isoelectric focusing and behaved entirely
      differently from lactoferrin. Preincubation of tumor target cells with the 87-kDa
      receptor inhibited competitively target cell recognition and cytotoxicity of
      human CD56+ NK and LAK cells.

PMID- 7829134
TI  - Adult T cell leukemia-derived factor/human thioredoxin protects endothelial F-2
      cell injury caused by activated neutrophils or hydrogen peroxide.
AB  - Adult T cell leukemia-derived factor (ADF), originally defined as an interleukin
      2 receptor/alpha (alpha) chain inducer produced by human T-lymphotropic virus
      type-I transformed cells, is identical to human thioredoxin (TRX). In this study,
      the protective effect of ADF/TRX on the cytotoxicity of endothelial cells caused
      by phorbol myristate acetate (PMA)-activated neutrophils or hydrogen peroxide
      (H2O2) was examined. When murine endothelial F-2 cells established from an
      ultraviolet light-induced tumor on a nude mouse were incubated with PMA-activated
      neutrophils or with 1 mM H2O2 for 6 hours, the cytotoxicity of F-2 cells was
      respectively 51 +/- 4% or 40 +/- 8% by the 51Cr releasing assay. Recombinant
      ADF/TRX (rADF/TRX) inhibited this cytotoxicity in a dose-dependent manner,
      although mutant ADF/TRX (cysteine 31 to serine), 2-mercaptoethanol and
      dithiothreitol did not. On a molar basis, rADF/TRX was more effective than
      glutathione but less effective than catalase. Immunoblotting analysis showed that
      treatment with 0.1 mM H2O2 induced murine TRX on F-2 cells. These findings
      indicate that ADF/TRX is an oxidative stress-inducible endogenous protein and
      rADF/TRX plays a protective role against activated neutrophils- or H2O2-induced
      endothelial cytotoxicity.

PMID- 7829135
TI  - Gamma-IFN and macrophage respiratory burst in Calomys callosus challenged with
      Trypanosoma cruzi bloodstream and metacyclic forms.
AB  - Parasitemia levels of Calomys callosus inoculated with a high dose (HBT) of 4 x
      10(3) Trypanosoma cruzi strain M226 bloodstream trypomastigotes (BT) exceeded
      those with the same inoculum of metacyclic trypomastigotes (MT) while a similar
      parasitemia was obtained with a low dose (LBT) of 5 x 10(2) of BT. Serum IFN
      gamma levels during the acute phase of infection were higher in the LBT
      inoculated group when compared with the group inoculated with HBT, while the IFN
      gamma levels in MT inoculated animals were close to uninfected controls.
      Spontaneous liberation of H2O2 of peritoneal macrophages explanted from animals
      on days 21 and 28 after infection was comparable to that of controls for HBT and
      LBT groups while that of the MT inoculated group was significantly higher.
      Phorbol Myristate Acetate (PMA) stimulation resulted in high H2O2 liberation
      specially in the infected groups. In vitro challenge with BT suppressed the small
      amount of spontaneous H2O2 release, while MT challenge stimulated this release to
      a limited degree in infected groups. In this animal model, interacting with a
      parasite strain isolated from the same host, macrophage activation as measured by
      H2O2 release was low, while the same strain had been previously observed to
      result in hyperactivation of mouse macrophages. We suggest that this distinctive
      behavior may be due to a host-parasite adaptation.

PMID- 7829136
TI  - Comparison of the ability of red cells sensitized with a bispecific anti-D x anti
      Fc gamma RIII Fab fragment to activate human K cells and peritoneal macrophages
      through Fc gamma RIII.
AB  - The functional activity of Fc gamma RIII on human K cells from peripheral blood
      was compared with that of Fc gamma RIII on peritoneal macrophages (PM) separated
      from the waste material of patients undergoing peritoneal dialysis. Fc gamma R
      function was assessed in vitro using human monoclonal IgG1 anti-D (AB5) or a
      bispecific antibody comprising Fab fragments of AB5 chemically linked to Fab
      fragments of monoclonal anti-Fc gamma RIII, 3G8 (AB5 x 3G8). In antibody
      dependent cell-mediated cytotoxicity (ADCC) assays, K cells mediated the lysis of
      papainized red cells sensitized with the AB5 x 3G8 bispecific antibody but not
      with AB5. In contrast, red cell lysis by PM was not promoted by AB5 x 3G8
      although AB5 was active. However, this lysis, being inhibited by monomeric IgG,
      was presumably mediated via Fc gamma RI. AB5 x 3G8 also failed to promote the
      binding and phagocytosis of both papainized and native red cells by PM although
      99% of red cells and over 90% of peritoneal cells bound the bispecific antibody.
      In marked contrast to K cells therefore, Fc gamma RIII on PM was unable to
      mediate functional interactions with red cells sensitized with anti-D x anti-Fc
      gamma RIII bispecific antibody.

PMID- 7829137
TI  - Necrotizing enteritis simulating Pig-Bel disease in northern India.
AB  - OBJECTIVE: A clinicopathological study of patients presenting with necrotizing
      enteritis, similar to the Pig-Bel disease of Papua New Guinea. METHODS: A
      clinicopathological study of 95 patients presenting in last ten years with acute
      abdominal pain with diarrhea and/or bleeding per rectum and vomiting and found to
      have lesions similar to Pig-Bel disease. RESULTS: 89% of the patients were young
      adult vegetarians from lower socio-economic strata. 94% of cases presented
      between May and August every year showing a marked seasonal variation. Jejunum
      was the most common site (95%) involved. Gross examination showed blackish brown
      'skip' lesions with gangrene and perforations. Histology showed marked necrosis
      and congestion of all the layers with mucosal ulcerations. CONCLUSION: A disease
      simulating Pig-Bel disease occurs in India. It is more common in young adult
      vegetarians and may have a different etiology from that proposed in endemic
      regions.

PMID- 7829138
TI  - Solid and cystic papillary neoplasm of pancreas--a report of seven cases.
AB  - OBJECTIVE: To study the clinico-pathological features of patients with solid and
      cystic papillary neoplasm of the pancreas. METHODS: The clinico-pathological
      features of solid and cystic papillary neoplasm of the pancreas were studied in
      seven fully documented and confirmed cases presented during the last seven years.
      RESULTS: All the patients were women with a median age of 18 years (range 12-40).
      Four presented with epigastric pain and three had a painless abdominal lump. The
      median duration of symptoms prior to presentation was 3 months (range 1-6). The
      tumor size ranged from 6-16 cm (mean 10 cm). Preoperative diagnosis was
      established by fine needle aspiration cytology in three patients. All the seven
      underwent resection. Pericapsular adhesions were found in two patients. All the
      patients were free of disease on follow-up ranging from 3-60 months (median 16
      mo). CONCLUSION: Occurrence in young females, solid and cystic areas on imaging,
      resectability in spite of large size, and good prognosis are the important
      features of this tumor.

PMID- 7829139
TI  - Fungal colonization of untreated peptic ulcer.
AB  - AIM: To evaluate the relationship between Candida and peptic ulcer. METHODS: One
      hundred consecutive patients with untreated peptic ulcer (81 with duodenal ulcer
      and 19 with gastric ulcer) were studied using histopathology, culture and fungal
      serology. Twenty subjects with non-ulcer dyspepsia were taken as controls.
      RESULTS: Forty seven patients (47%) with peptic ulcer were colonized by Candida
      as compared to 3 patients (15%) with non ulcer dyspepsia (p < 0.05). Confluent
      growth of Candida on culture of gastric aspirate or biopsy from ulcer edge was a
      more sensitive method for diagnosis of peptic ulcer-associated candidiasis than
      histological examination. There was no significant difference in the prevalence
      of Candida isolation in relation to age or sex of the patients, smoking habit and
      alcoholism. Large ulcers (> 2 cm) were, however, more often colonized by Candida
      (75%) than smaller ones (43%) (p < 0.05). Candida albicans was the commonest
      species isolated (60%). Invasive candidiasis was associated with Candida
      agglutinin titer of 1:128 in 81% of cases. CONCLUSION: Candida colonization rate
      in peptic ulcer is significantly higher than in non-ulcer dyspepsia.

PMID- 7829140
TI  - Nonsurgical drainage for biliary obstruction.
AB  - Biliary obstruction is a common and potential fatal condition. Its pathological
      effects include depressed immunity, impaired phagocytic activity and reduced
      Kupffer cell function with consequent endotoxemia, septicemia and renal failure.
      Over the last decade however, non-surgical biliary drainage procedures performed
      with radiologic or endoscopic guidance emerged as alternative to surgical of
      therapy in many situations, particularly palliation of malignant strictures
      because of their lower morbidity and mortality rates. Endoscopic stent placement
      is preferred over percutaneous transhepatic catheter drainage in general. If
      endoscopic procedure is not possible or fails percutaneous transhepatic biliary
      drainage or combined radiological-endoscopic procedure should be employed.
      Surgery is currently reserved only for curative resection/palliative drainage in
      young and fit patients. Preoperative biliary drainage aimed at reducing post
      operative morbidity and mortality is not universally accepted and needs further
      study. Benign strictures are increasingly being dilated non-surgically with
      temporary stenting, especially in patients with failed surgery, recurrent
      strictures, contraindication to surgery and pre-liver transplant strictures eg
      primary sclerosing cholangitis. A cohesive team consisting of a surgeon, a
      radiologist and an endoscopist is required to achieve the best possible results.

PMID- 7829141
TI  - Esophageal endoprosthesis in malignant stricture.

PMID- 7829142
TI  - Esophageal involvement in pemphigus vulgaris.
AB  - Twenty five patients with pemphigus vulgaris were prospectively studied for
      esophageal involvement by endoscopic examination. Eighteen (72%) had esophageal
      involvement; the majority of the lesions were bullae. Histological examination
      showed acantholysis of the cells and exuberant inflammation.

PMID- 7829143
TI  - Gastric acid study in patients operated on for perforated duodenal ulcer.
AB  - OBJECTIVES: To determine the acid secretory status of patients operated on for
      perforated duodenal ulcer, with or without prior history suggestive of acid
      peptic disease. METHOD: Basal and peak acid output were measured in 48 patients
      with perforated duodenal ulcer who were treated by simple closure alone, 10
      patients with uncomplicated chronic duodenal ulcer and 30 normal controls.
      Patients operated on for perforated duodenal ulcer were analyzed according to
      presence (or absence) and duration of prior history of acid-peptic disease.
      RESULTS: Peak acid output was similar in controls and patients with perforated
      duodenal ulcer with no prior symptoms. However, patients with prior symptoms had
      significantly higher peak acid output, similar to those with uncomplicated
      duodenal ulcer. CONCLUSION: Patients with perforated duodenal ulcer with no
      antecedent history of acid-peptic disease have normal gastric acid output. These
      patients may therefore have other etiological factors for their ulcers.

PMID- 7829144
TI  - Pseudomyxoma peritonei: a report of eight cases.
AB  - OBJECTIVE: To assess the effectiveness of surgical treatment for pseudomyxoma
      peritonei. DESIGN: Retrospective analysis. SETTING: Referral center. PATIENTS:
      Eight patients with pseudomyxoma peritonei, five with mucinous tumors of the
      ovary and three with mucoceles of the appendix. INTERVENTION: All patients
      underwent cytoreductive surgery with removal of source i.e. panhysterectomy with
      appendicectomy in 5 and appendicectomy in 3. Systemic chemotherapy was used in 6
      and systemic plus intraperitoneal chemotherapy in one case. RESULTS: Over 18 to
      86 months' follow up, two patients died (at 18 and 24 mo) and 2 are alive with
      recurrence. Recurrence occurred only in those with inadequate clearance of
      mucinous material at the initial operation. The remaining 4 patients are free of
      disease. CONCLUSION: Aggressive surgical therapy with-chemotherapy is effective
      in providing long-term relief or cure in pseudomyxoma peritonei.

PMID- 7829145
TI  - Evaluation of culture techniques for detection of spontaneous bacterial
      peritonitis in cirrhotic ascites.
AB  - This prospective study was done in cirrhotic patients to evaluate ascitic fluid
      culture techniques by the conventional method and by an alternate method of
      bedside ascitic fluid inoculation into blood culture bottles, with an aim to
      improve bacteriological diagnosis of spontaneous bacterial peritonitis (SBP). Of
      the 300 patients who were evaluated, 43 who had a total leukocyte count greater
      than 500/mm3 or a polymorphonuclear cell count greater than 250/mm3 in ascitic
      fluid were included. There were 30 episodes of SBP in 28 patients and another 15
      patients had culture-negative neutrocytic ascites (CNNA). Escherichia coli was
      the commonest organism cultured, being found in 60%. There was significantly
      greater (p < 0.001) ascitic fluid culture positivity with direct inoculation into
      blood culture bottles, i.e. 66.7% compared to 31.1% by conventional method at 48
      hours, and this was evident even 24 hours after inoculation i.e. 33.3% positivity
      compared to 4.4%. Bacteremia was present in 53.3% of patients with SBP and 33.3%
      with CNNA. Ascitic fluid inoculation directly into blood culture bottles leads to
      a significantly increased percentage of culture positivity and reduces the time
      needed for detection of SBP from 48 to 24 hours.

PMID- 7829146
TI  - Multiple endocrine neoplasia type-1.
AB  - A 38-year-old man with multiple endocrine neoplasia type-1 (Wermer's syndrome) is
      described. The patient had refractory duodenal ulcers and raised basal acid
      output (55 mmol/hour) and fasting serum gastrin (1190 pg/ml). Abdominal CT scan
      revealed mass lesions (gastrinomas) in the head of the pancreas. He also had
      persistent hypercalcemia, hypophosphatemia, right ureteric calculi, increased
      urinary calcium and phosphorus and enlarged parathyroids on ultrasound and CT of
      the neck. Parathormone level was raised, but the pituitary gland was normal on CT
      scan of the head. The patient was managed initially with histamine H2-blockers,
      omeprazole and parathyroidectomy; enucleation of the tumor masses in the pancreas
      was done subsequently.

PMID- 7829147
TI  - Antral diaphragm with achalasia cardia.
AB  - A 50-year-old woman presented with gastric inlet and outlet obstruction due to
      achalasia cardia and antral mucosal diaphragm, respectively. The diagnosis was
      based on typical radiological features, endoscopy and full-thickness histology of
      biopsy at postmortem.

PMID- 7829148
TI  - Large villous adenoma of the duodenum.
AB  - A 27-year-old man, who had symptoms of gastric outlet obstruction, was found on
      endoscopy to have a large duodenal polyp which on histology was diagnosed as
      villous adenoma. The tumor was resected surgically and the patient remained
      asymptomatic until two years later.

PMID- 7829149
TI  - Gastric carcinoma presenting as solitary cutaneous metastasis.
AB  - We report a patient with gastric adenocarcinoma presenting with a cauliflower
      like large papillomatous cutaneous metastases on the nape of the neck.

PMID- 7829150
TI  - Fibrolamellar hepatocellular carcinoma.
AB  - Fibrolamellar hepatocellular carcinoma, a histological variant of hepatocellular
      carcinoma, distinct pathological and clinical features and a better prognosis
      than other types of hepatocellular carcinoma. We report here a patient who was
      treated on successful surgically.

PMID- 7829151
TI  - Primary Hodgkin's disease of the small intestine: does it really exist?

PMID- 7829152
TI  - Epidemic of Vibrio cholerae 0139 in Calcutta.
AB  - As one of large outbreaks of cholera-like illness in the Indian subcontinent,
      Calcutta and its neighbouring areas experienced an unprecedented epidemic due to
      a new strain of V. cholerae non-01, designated as V. cholerae 0139 Bengal, since
      January 1993. This epidemic predominantly affected the adult population of
      Calcutta as evidenced by the hospitalization of more adults at the Infectious
      Disease Hospital, Calcutta (IDH), which bore the main brunt of the epidemic in
      and around Calcutta. During the peak of the epidemic about 180 to 300 diarrhoea
      patients were admitted daily at the IDH. Of the 807 patients screened, 407 were
      positive for V. cholerae 0139 and majority (82.8%) of the cases were > 10 yr of
      age. Severe dehydration was recorded in 85.5 per cent of the cases.

PMID- 7829153
TI  - Outbreak of cholera due to Vibrio cholerae 01 in Orissa state.
AB  - During May-June 1993, an outbreak of acute diarrhoea resulting in deaths
      primarily in adults was reported in two districts of Orissa state.
      Epidemiological and microbiological investigations revealed that this outbreak
      was caused by V. cholerae 01 biotype EITor. V. cholerae 01 strains were uniformly
      resistant to furazolidone.

PMID- 7829154
TI  - Hypereosinophilia in association with pulmonary tuberculosis in a rural
      population in south India.
AB  - In a prospective study conducted in four villages of North Arcot Ambedkar
      district of Tamil Nadu in south India over a 5 yr period from 1981-86, 279
      patients were detected to have pulmonary tuberculosis (PTB). Thirty one of them
      were found to have associated hypereosinophilia (HE) with total blood eosinophil
      level of > or = 2000 per cumm; besides cough with expectoration they also
      complained of dyspnoea and wheeze. Twelve of the 18 patients with intestinal
      parasites had remission with deworming agents alone. The other 6 non responsive
      patients like the 13 who did not have parasitic infestation, needed treatment
      with diethylcarbamazine for eosinopenic remission and thus could be classified as
      patients of tropical pulmonary eosinophilia (TPE). The association of
      hypereosinopilic state as a whole as well as TPE with tuberculosis as compared to
      that prevalent in the general population was found to be highly significant (P <
      0.001). The frequent association of TPE with tuberculosis as observed by us
      suggests the possibility of an early hypersensitivity reaction to mycobacterial
      antigens triggering a florid TPE state in susceptible patients from an area
      endemic for filariasis. A similar mechanism may also operate in cases of
      pulmonary eosinophilia induced by other helminths in areas where they are
      endemic.

PMID- 7829155
TI  - Human immunodeficiency virus infection related to blood transfusion service.
AB  - The prevalence of transmissible viruses, human immunodeficiency (HIV) and
      hepatitis B (HBV) in blood donors, recipients and blood bank staff in a Calcutta
      (eastern India) based blood bank and transfusion centre has been studied from
      1987-93. HIV seropositivity of blood donors was of recent emergence and was low.
      Recipients of blood and blood components frequently i.e., haemophilics showed a
      progressive increase in HIV seropositivity since 1988 whereas in thalassaemics
      the emergence of HIV seropositivity was noted only in 1992. Blood bank staff were
      seronegative. HBV which has a similar portal of entry as HIV, had a higher
      prevalence in blood donors, recipients of blood/components and blood bank staff.

PMID- 7829156
TI  - Copper levels & reactive oxygen species in uterine flushings in copper
      intrauterine contraceptive device users.
AB  - Copper levels were estimated in the uterine flushings in 15 copper 'T' 200 device
      acceptors. There was a statistically significant difference in the preinsertion
      and one week post insertion values (P < 0.001). This also corresponded to a high
      level of generation of reactive oxygen species. The levels of reactive oxygen
      species were similar to preinsertion values at 4 and 12 wk. The copper values
      declined over the 3 months but were still higher at 12 wk as compared to
      preinsertion levels and this difference was statistically significant. Hence
      addition of copper to the intrauterine device besides enhancing the contraceptive
      efficacy, perhaps also plays an important role in microbicidal activity and helps
      in overcoming the infection introduced at the time of insertion.

PMID- 7829157
TI  - Mycotic aneurysms of the intracranial vessels.
AB  - The salient clinical and pathological features are reported of Aspergillus
      cerebral aneurysms in four young women who had undergone intra-abdominal surgery
      under spinal anaesthesia and developed clinical features of meningitis 7-16 days
      postoperatively. The circle of Willis showed ruptured aneurysm in the basilar
      artery and its branches. The role of iatrogenic factors in the pathogenesis of
      Aspergillus cerebral aneurysms is highlighted.

PMID- 7829158
TI  - Clinical utility of serum thyroglobulin in metastatic disease.
AB  - We examined the usefulness of serum thyroglobulin (Tg) levels in 196 patients
      with metastatic disease. Of these, 51 patients had a thyroidal primary (40
      differentiated, 7 medullary and 4 undifferentiated), 35 patients had a
      nonthyroidal primary and in 110 patients the primary site was not known. Serum Tg
      was raised in 74.5 per cent (38 of 51) patients with carcinoma of the thyroid and
      in 92.5 per cent (37 of 40) patients with differentiated thyroid carcinoma (DTC).
      Twelve (34.3%) patients with proved nonthyroidal malignancies and 34 (30.9%)
      patients with unknown primary origin had elevated serum Tg levels. Of the 110
      patients with unknown primary site thyroidal primary in 10 patients (all with
      elevated serum Tg levels) and nonthyroidal primary in 38 patients (7 had raised
      serum Tg levels) could be established. The sensitivity (for DTC) and the
      specificity (for nonthyroidal primary) of serum Tg estimation were 94.0 per cent
      (47 of 50) and 74.0 per cent (54 of 73) respectively and for patients with
      distant metastases were 100 (29 of 29) and 85.1 per cent (40 of 47) respectively.
      The positive and the negative predictive values of serum Tg were 71.2 (47 of 66)
      and 94.7 per cent (54 of 57) respectively and for patients with distant
      metastases were 80.6 (29 of 36) and 100 per cent (40 of 40) respectively. Our
      findings suggest that for patients presenting with metastases (particularly
      distant metastases) of an unknown primary site, serum Tg estimation is of great
      value to identify or rule out the involvement of the thyroid as the primary
      organ.

PMID- 7829159
TI  - Lipid-lowering efficacy of psyllium hydrophilic mucilloid in non insulin
      dependent diabetes mellitus with hyperlipidaemia.
AB  - The effect of the administration of 3.5 g of psyllium husk twice daily for 90
      days was investigated in 24 patients of non insulin dependent diabetes mellitus
      (NIDDM) with hyperlipidaemia. After 90 days of treatment, psyllium was withdrawn
      and the patients were followed up for a further 90 days. Psyllium significantly
      decreased the levels of total cholesterol (TC; 19.7%), low-density lipoprotein
      cholesterol (LDL-C; 23.7%), triglycerides (TG; 27.2%) and the ratio of LDL-C to
      high-density lipoprotein cholesterol (HDL-C; 24.1%) and the lowering was
      sustained even up to 90 days after cessation of treatment. The level of HDL-C
      also showed a significant increase of 15.8 per cent but this effect was not
      sustained after cessation of treatment. The compliance was very good and no
      adverse effects were observed. This study indicated that psyllium husk is an
      effective and well tolerated adjunct to diet for the treatment of mild to
      moderate hyperlipidaemia in NIDDM patients.

PMID- 7829160
TI  - Prevalence of sickle cells in Irula, Kurumba, Paniya & Mullukurumba tribes of
      Nilgiris (Tamil Nadu, India).
AB  - A total of 1377 tribals, comprising Irulas (536), Paniyas (196), Kurumbas (87),
      Mullukrurumbas (156) and Soligas (402), living in the Nilgiris, Tamil Nadu, India
      were studied for sickle cell trait between 1981-85. Patients attending various
      tribal clinics at Arayure, Kozhikarai, Kothagiri and Biligiri Rengan hills for
      various ailments were screened at random by solubility test and by acetate paper
      electrophoresis, if required. HbAS carrier frequency was 30-37.8 per cent in all
      the tribals studied except Kurumbas (19.5%). The frequency of carriers were more
      (37.8%) on the western part of Nilgiris (Nedungode, Kappala and adjoining
      regions) than the eastern part (30%). Further, the prevalence of carriers was
      higher (47-49%) in the 10-19 yr age group amongst Paniyas and Mullukurumbas
      living in the western part of Nilgiris. An episodic, epidemic of malaria so
      rampant during the early part of this century in the western parts of Nilgiris
      might have eliminated many children with HbAA and hence the higher frequency of
      HbAS in this particular age group.

PMID- 7829161
TI  - In vivo effects of isatin on certain enzymes, lipids & serotonergic system of rat
      brain.
AB  - Isatin (10 microM) strongly inhibited the activity of rat brain monoamine oxidase
      B (MAO-B) in vitro. At millimolar concentrations (1-10 mM) it inhibited brain
      acetylcholinesterase (AChE) and sodium, potassium-adenosine triphosphatase (Na+,
      K(+)-ATPase) activity also. However, isatin did not affect these enzymes after
      both acute and chronic treatments in vivo. Administration of isatin to rats at
      300 mg/kg body weight for 2 and 6 h significantly raised brain serotonin levels.
      Chronic treatment for 20 days resulted in enhanced brain glycolipids and
      plasmalogen levels. There was no change in the levels of 5-hydroxy indole acetic
      acid (5 HIAA), phospholipids, cholesterol and gangliosides under these
      conditions.

PMID- 7829162
TI  - Development of a conjoint phage typing & biotyping schema for Salmonella enterica
      serovar Senftenberg (S. senftenberg) & the correlation of biotypes with phage
      types.
AB  - A total of 287 strains of S. senftenberg received from various parts of India
      during 1969 to 1992 were phage typed using six lysogenic phages. The typability
      was 90.3 per cent and 14 different phage types could be defined excluding a small
      group of untypable strains. A biotyping scheme was developed utilising six
      characters and 13 biotypes could be defined. Stern's glycerol medium proved to be
      the best discriminatory medium. Diversity indeces of phage typing and biotyping
      schemes were 0.868 and 0.503 respectively. Better discrimination was obtained
      when phage types were subdivided into different biotypes with a diversity index
      of 0.931. The schemes were found stable, reproducible and epidemiologically
      useful.

PMID- 7829163
TI  - Evaluation of potency of inactivated cholera vaccine by mouse protection assay &
      antibody induction method.
AB  - Twenty one batches of whole cell inactivated cholera vaccine manufactured at
      Central Research Institute, Kasauli were evaluated for potency by mouse
      protection assay (MPA) and antibody induction method. In the antibody induction
      method the sera of immunized mice were screened for the presence of antibodies
      against Vibrio cholerae by microagglutination (MA) test and IgG ELISA. The number
      of organisms estimated by MPA were correlated with agglutinating and neutralizing
      antibodies against individual serotypes by MA and ELISA respectively. Correlation
      coefficient(r) of 0.692 and 0.815 were observed for the titres evaluated by MA
      and ELISA when compared with standard MPA method for the serotype Ogawa.
      Similarly r values of 0.925 and 0.849 were observed for titres evaluated by MA
      and ELISA when compared with standard MPA method for the serotype Inaba. Antibody
      induction method can be as an alternative method for determining the potency of
      inactivated cholera vaccine.

PMID- 7829164
TI  - An outbreak of multidrug resistant Salmonella typhimurium in Delhi (India).
AB  - A total of 85 patients with multidrug resistant S. typhimurium were isolated
      between May and September 1991 at the Sir Ganga Ram Hospital, New Delhi, India.
      Fifty eight (72.5%) patients out of 80 stool culture positives suffered from
      enteritis and 23 (39.6%) of them settled with oral rehydration therapy alone. All
      strains were sensitive to 4 aminoquinolones (oflaxcin) but five were resistant to
      third generation cephalosporin (Cefotaxime; MIC between 50-75 micrograms/ml)
      whereas 88-96 per cent isolated were resistant to most of the other antibiotics.
      The convalescent carrier rate was prolonged with the use of antibiotics. The
      phage type of S. typhimurium isolated from the index and other cases was 178 and
      multidrug resistance strains had seven plasmids (1.2 to 16 kb). Barrier nursing
      and sodium hypochlorite disinfection helped in limiting the outbreak.

PMID- 7829165
TI  - Monoclonal gammopathies in asymptomatic HIV-seropositive donors.
AB  - Twenty two HIV antibody ELISA reactive serum samples from blood donors were
      subjected to Western blot (WB) test, out of which 12 sera were found WB positive,
      five were WB-indeterminate and five were WB-negative. Electrophoresis on agar gel
      and polyacrylamide gel (PAG) was done in all ELISA reactive sera. Two of the 12
      WB-positive and one of the five WB-indeterminate donors showed presence of
      monoclonal (M) immunoglobulin component and which was identified as of IgG
      isotype on immunoelectrophoresis (IEP). Sera with 'M' component demonstrated
      decreased levels of IgA and IgM whereas other sera showed polyclonal increase of
      immunoglobulins. The paraproteins observed in these patients are possibly a
      reflection of B-cell overactivation.

PMID- 7829166
TI  - Use of polyclonal anti-myeloperoxidase antibody in myeloid lineage determination.
AB  - This study reports the production of a rabbit polyclonal antibody to
      myeloperoxidase (MPO) and its use in ascertaining the myeloid lineage of blasts
      in leukaemia. Comparison of the immunocytochemical stain using the anti-MPO
      antibody with the routine cytochemical methodology showed that the former was
      more sensitive. In all subtypes of acute myeloid leukaemia (AML; 72 patients, M1
      M6) greater number of MPO positive blast cells were observed by
      immunocytochemistry, the highest being in the promyelocytic leukaemia. It was
      also extremely specific for cells of the myeloid lineage as it did not react with
      blasts from acute lymphoblastic (50 patients) and megakaryoblastic leukaemias (1
      patient). In addition, it proved most useful for the lineage determination of
      blasts from patients with undifferentiated acute leukaemias (AUL) and those with
      chronic myeloid leukaemia in blast crisis (CML-BC). Out of 8 patients of AULs, 6
      were classified as acute myeloblastic leukaemia due to their reactivity to the
      anti-MPO antibody. Similarly, out of 12 patients of chronic myeloid leukaemia in
      blast crisis, blasts from 8 showed reactivity to this antibody and thus could be
      identified as belonging to the myeloid lineage and/or of the mixed blast crisis
      type.

PMID- 7829167
TI  - Short term methotrexate therapy in psoriasis.
AB  - Data on 82 psoriatics (62 males and 20 females) with either chronic recalcitrant,
      erythrodermic, generalized pustular or severe palmoplantar psoriasis treated with
      methotrexate (MTX) have been reviewed. MTX was given in a single oral weekly dose
      of 3.75-30 mg based on body weight. Seven patients with a relative
      contraindication for MTX use were also treated safely with MTX. An attempt was
      made to withdraw MTX as quickly as possible with the intention of providing drug
      free period of 4-6 months coinciding this period with the seasonal remissions in
      disease activity. MTX could be withdrawn in up to 90 per cent patients within an
      average of 25 wk. The total cumulative dose could also be reduced by this method
      as also the need to repeat liver biopsies.

PMID- 7829168
TI  - Induction of N-methyl-D-asparate receptor mediated c-fos protein in the rat brain
      by incomplete ischaemia.
AB  - The expression of c-fos protein was examined by means of immunocytochemistry in
      the rat brain following incomplete ischaemia, to elucidate the molecular
      mechanisms of post-ischaemic neuronal death and of the modulated
      neurotransmission of surviving neurons. Incomplete ischaemia was produced by
      permanent unilateral or bilateral common carotid artery (CCA) occlusion. After 1
      h of unilateral occlusion, the level of c-fos protein-like nuclear
      immunoreactivity increased in cortical neurons ipsilateral to the insult,
      especially in cingulate and piriform cortices. The reactivity peaked at 3-6 h,
      and was undetectable after 3 days. A number of scattered immunostained neurons in
      the ipsilateral subiculum, CA 1 and dentate gyrus became visible after 1 day. The
      effect reached a peak between 1-3 days, then returned to basal levels by 7 days.
      Bilateral CCA occlusion showed a similar distribution of immunoreactivity, but on
      both hemispheres. Immunoreactive neurons were more numerous and intensely stained
      but more transient. The induction of c-fos was completely blocked or reduced by
      treatment with MK-801. Our results suggest that c-fos expression after CCA
      occlusion is NMDA receptor mediated, and that it has a specific role in neurons
      after ischaemic insult.

PMID- 7829169
TI  - Expression of brush border enzymes in ethanol fed rat intestine.
AB  - The effect of feeding ethanol daily for 40 days was studied on various brush
      border enzymes in rat intestine. Brush border alkaline phosphatase (AP), lactase,
      gamma-glutamyltranspeptidase (gamma-GTP), p-nitrophenyl (PNP)-beta-D
      galactosidase (P < 0.01) and sucrase (P < 0.001) were significantly enhanced
      while leucine aminopeptidase and PNP-beta-D-glucosidase activities were unaltered
      in ethanol fed rats compared to the controls. Kinetic studies revealed that an
      increase in Vmax together with a decrease in affinity in case of gamma-GTP and an
      increase in Vmax for AP and sucrase were responsible for the observed stimulation
      of enzyme activities in ethanol administered rats. Significant changes in enzyme
      activities were observed in different populations of enterocytes along the crypt
      villus unit in the ethanol fed animals. These observations suggest that ethanol
      feeding modifies the brush border enzymes in rat intestine but the underlying
      mechanisms seem to be distinct in differentiating enterocytes.

PMID- 7829170
TI  - In vitro biomechanical evaluation of anterior cruciate ligament graft
      substitutes.
AB  - The study was undertaken to identify an isoelastic graft material for the
      anterior cruciate ligament (ACL). Double transducer ultrasonic pulse transmission
      method was employed for determining the elastic properties of normal ACL in
      comparison with various graft materials like the central third of the patellar
      tendon, semitendinosus and iliotibial band in different twisted forms. The
      elasticity and rigidity parameters were studied by taking ACL as being equal to
      100 per cent. Our results indicated that the strength of the graft depended upon
      the density of the collagen bundles and elastic properties depended upon the
      pretensioning of the graft.

PMID- 7829171
TI  - N-nitrosamines in Indian beers.
AB  - Presence of volatile N-nitrosamines in beer and other alcoholic drinks are well
      documented in developed countries. Analysis of 120 beer samples of various
      brands/batches showed positivity for N-nitrosodimethylamine (NDMA) in more than
      100 samples. The overall mean of 3.6 ppb of NDMA is higher than those currently
      found in Western countries. Since N-nitrosamines are proven carcinogens in
      animals at several sites it is necessary to keep their levels of exposure to as
      low as possible.

PMID- 7829172
TI  - Diagnostic and prognostic significance of serum and tissue trace elements in
      breast malignancy.
AB  - 50 cases of breast malignancy constituted the study group. 26 age and sex matched
      formed the control group. Serum and tissue trace element viz copper, zinc,
      selenium and molybdenum levels were estimated by atomic absorption photometry.
      The study group showed significant hypercupremia and molybdenemia, hypozincaemia
      and hyposeleniamia. The reversal of trend was documented after therapy. The
      tissue level of copper and molybdenum was high and zinc and selenium was low. An
      association between serum and tissue level of trace element, stage, histological
      differentiation was observed. It was postulated that levels of trace elements may
      help in diagnosis and prognosis of disease.

PMID- 7829173
TI  - Antibiotic susceptibility pattern of gonococcal isolates.
AB  - A total of 151 isolates of gonococcal urethritis were processed for antibiotic
      susceptibility pattern by single disc diffusion technique. 17.88% isolates were
      found to be penicillinase producing Neisseria gonorrhoeae. Only 82.12% and 94.04%
      of the isolates were sensitive to penicillin and gentamicin respectively, whereas
      all the isolates were sensitive to fluoroquinolones namely norfloxacin and
      ciprofloxacin.

PMID- 7829174
TI  - Nosocomial infection.

PMID- 7829175
TI  - Retinal vein occlusion.
AB  - In this review of the retinal vein occlusion (RVO), I have summarized recent
      advances on several controversial and clinically important topics: classification
      of RVO into six distinct clinical entities; pathogeneses and demographic
      characteristics of various types of RVO; differentiation of non-ischemic from
      ischemic central retinal vein occlusion (CRVO); differentiation of hemi-CRVO
      (HCRVO) from major branch RVO (BRVO); and the course, complications and
      management of various types of RVO.

PMID- 7829176
TI  - Effect of flurbiprofen sodium on pupillary dilatation during scleral buckling
      surgery.
AB  - Maintenance of pupillary dilatation is necessary for success of scleral buckling
      procedures. The efficacy of 0.03% flurbiprofen in preventing intraoperative
      miosis was evaluated by a prospective randomized, double-masked controlled trial
      of 60 patients. Thirty patients received 0.03% flurbiprofen 6 times at 15 minute
      intervals 90 minutes preoperatively in addition to the routine dilation regimen.
      The treated group had a mean pupillary decrease of 1.88 mm and the control group
      had a decrease of 1.57 mm (p > 0.05). Flurbiprofen did not affect the pupillary
      size at any step of the surgery. Factors such as age of the patient, lens status,
      number of cryo applications, duration of surgery, and the size and extent of
      buckle were assessed. The use of flurbiprofen did not affect the mean pupillary
      change for any of these groups. Preoperative use of flurbiprofen does not
      significantly decrease intraoperative miosis during scleral buckling procedures.

PMID- 7829177
TI  - Familial nanophthalmos: management and complications.
AB  - Nanophthalmos is a rare form of congenital hypermetropia, in which, the
      individual is at a high risk of developing angle-closure glaucoma. We report a
      family of nanophthalmos affecting a brother and sister, as confirmed by biometry.
      Genetic analysis revealed an autosomal recessive mode of inheritance. The sister
      developed angle-closure glaucoma, which was refractory to medical and laser
      therapy. She underwent surgical interventions which resulted in complications.
      The clinical presentation, management, and complications encountered are
      discussed.

PMID- 7829178
TI  - Phacolytic glaucoma--its treatment by planned extracapsular cataract extraction
      with posterior chamber intraocular lens implantation.
AB  - Phacolytic glaucoma has traditionally been treated with intracapsular lens
      extraction to avoid any anaphylaxis. Various mechanisms have been described for
      the rise of intraocular pressure in these cases. The present study was undertaken
      to evaluate the response of extracapsular cataract extraction (ECCE) with
      posterior chamber intraocular lens implantation (PC IOL) in five cases of
      phacolytic glaucoma that occurred between March 1989 and August 1990. A planned
      extracapsular cataract extraction with can-opener capsulectomy was done in all
      the cases with placement of a sulcus-fixated modified J-loop Sinskey design
      intraocular lens. With a mean follow-up period of two years, all patients (100%)
      maintained a normal postoperative intraocular pressure of less than 20 mm Hg
      without any additional medical therapy. The final best-corrected visual acuity in
      4 cases (80%) was 6/12 or better, while in one case it was 6/24 due to a senile
      maculopathy. These results show that ECCE with PC IOL implantation is a safe and
      efficacious method of visual rehabilitation in cases of phacolytic glaucoma.

PMID- 7829179
TI  - Effect of U74006F (Tirilazad Mesylate) in rabbit eyes after argon laser
      trabeculoplasty.
AB  - A new free radical scavenger, U74006F (Upjohn Company, Kalamazoo, MI, USA) was
      studied to determine if it would have a beneficial effect on preventing
      intraocular pressure (IOP) spikes and reducing blood-aqueous barrier (BAB)
      breakdown in rabbits after argon laser trabeculoplasty (ALT). The post-ALT IOP
      averaged 24.7 mm Hg (+/- 3.8 mm Hg; N = 6) and 30.3 mm Hg (+/- 6.9 mm Hg; N = 7)
      at 1 hour (p = 0.097) and 22.7 mm Hg (+/- 1.9) and 27.3 mm Hg (+/- 7.0 mm Hg) at
      3 hours in the U74006F and vehicle groups (p = 0.137), respectively. By 48 hours,
      the IOP averaged 12.8 +/- 2.2 mm Hg in the U74006F group and 12.4 +/- 2.4 mm Hg
      in the vehicle group (P = 0.757). The aqueous fluorescein permeability (AFP)
      between lasered and unlasered eyes was determined for the U74006F and vehicle
      treated groups by aqueous fluorophotometry. Prelaser or baseline AFP was
      determined for the U74006F (-0.236 +/- 0.236) and vehicle (-0.145 +/- 0.237)
      groups (p = 0.505). At day 2 posttreatment, the U74006F group and the placebo
      group both reported similar AFP of 5.109 +/- 4.831 and 5.680 +/- 4.280 (p =
      0.827), respectively. At one week post-ALT, AFP for the U74006F group (0.109 +/-
      0.367) had returned close to baseline, while that of the vehicle group (0.426 +/-
      0.511) was still quite elevated (p = 0.220). U74006F appears to be beneficial in
      the prevention of acute elevation of IOP following ALT but not in the prevention
      of Blood-Aqueous Barrier (BAB) breakdown.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7829180
TI  - Lid load operation in facial palsy.
AB  - In 24 patients with irreversible lagophthalmos, gold weights ranging from 0.8 to
      1.7 g were implanted in the upper lids, under local anaesthesia. With a follow-up
      period ranging from 2 1/2 to 4 years (average, 3 years), the results of the
      implantation were gratifying in 23 patients. While corneal irritation and
      epiphora was reduced and the loaded upper eyelid allowed patients to blink
      voluntarily.

PMID- 7829181
TI  - Practical approach to a patient with epiphora.

PMID- 7829182
TI  - Deck-chairs: putting a finger on the problem, rather than in it.
AB  - Although often portrayed as something of a joke, injuries sustained in the
      setting-up and use of deck-chairs can have fairly serious consequences. Six
      patients who sustained finger injuries in some of London's Royal Parks during the
      Summer are presented together with data from the Department of Trade and Industry
      suggesting that, taken throughout the country as a whole, large numbers of
      injuries may be occurring. Notably, four of our patients were foreign tourists
      who may be less familiar with the traditional wooden folding deck-chair.
      Surprisingly no British Standards Institute (BSI) guidelines exist relating to
      deck-chair safety. These finger injuries can have marked morbidity if they
      involve victims who depend upon manual dexterity in their work or hobbies.

PMID- 7829183
TI  - Cross-leg free muscle flaps for reconstruction of open fractures of the tibia.
AB  - In two patients in whom the injured leg was not suitable for reconstruction using
      a routine free tissue transfer, a cross-leg free muscle flap was used, i.e. the
      vessels of a free muscle flap were anastomosed to donor vessels on the uninjured
      leg and the muscle flap used to reconstruct a defect on the opposite leg. Both
      operations were successful, with the transferred muscle becoming well
      vascularized from the recipient bed at the site of injury. In both cases, use of
      the uninjured leg to transfer the free flap caused minimal morbidity.

PMID- 7829184
TI  - The epidemiology of fractured femurs and the effect of these factors on outcome.
AB  - We have analysed 250 cases of fractured shaft of the femur with the objective of
      highlighting any preventative measures and anticipating morbidity associated with
      cause and type of injury. The younger patients typically injure themselves as
      pedestrians, motorcyclists and bicyclists in Summer. The older patients tend to
      have falls in late Summer and Winter. The outcome varies depending on the cause,
      type and age of the injured person. The greatest morbidity was found in high
      velocity accidents involving motorcyclists, pedestrians and car accidents. Knee
      flexion is a particular problem with these injuries and we are currently using
      continuous passive motion in conjunction with a continuous opiate infusion where
      this is likely to be a problem. The results also suggest that the mechanism of
      injury and its possible prevention, particularly in motorcycle design, could be
      as important as the type of treatment. Elderly females following falls also form
      a distinct group, suggesting that osteoporosis is a major factor with the best
      outcome associated with treatment by internal fixation. We feel that age alone
      should not be a reason for exclusion from intramedullary fixation and this merits
      further study.

PMID- 7829185
TI  - Injuries of the lower cervical spine associated with widening of the spinal
      canal.
AB  - In this paper, we present 17 cases with injury of the lower cervical spine
      associated with widening of the spinal canal. This was due to bilateral fracture
      of the pedicles of the neural arch, where the body of the injured vertebra is
      displaced anteriorly, while the posterior elements of the vertebra remain in
      situ. Eleven patients were male and six female, between 32 and 53 years of age.
      Ten of them were involved in a road traffic accident, while seven had a fall on
      the head. We distinguished two types of injury: Type I with anterior displacement
      of the injured vertebra (12 cases) and Type II with impaction of the injured
      vertebral body on the vertebra below (five cases). Thirteen patients were without
      neurological complications, two had root lesions, while two had tetraplegia from
      a point higher than the injury level. This was due to an extensive anterior
      displacement of the injured vertebra and of the whole spine above, associated
      with dislocation of the vertebra above the injury and damage to the spinal cord.
      The cases with anterior displacement of the injured vertebra are unstable and
      need spinal fusion after prior reduction, while the rest can be treated non
      operatively with head traction followed by bracing until stable intervertebral
      union is achieved.

PMID- 7829186
TI  - 'The broken halo sign': a fractured calcified ring as an unusual sign of
      traumatic rupture of the thoracic aorta.
AB  - Two elderly patients, involved in separate motor vehicle accidents, sustained
      blunt chest injury resulting in rupture of their thoracic aortas. The initial
      chest radiographs showed the presence of a calcified ring fractured in two places
      with lateral displacement of a calcified fragment by haematoma. This 'broken halo
      sign' is a radiographic sign not previously well described in the literature. The
      presence of a disrupted aortic ring in the elderly patient, associated with the
      appropriate mechanism of injury, should alert the clinician to the potential
      diagnosis of traumatic rupture of the thoracic aorta (TRTA).

PMID- 7829187
TI  - Comparative evaluation of the two positions used for imaging of trochanteric
      fractures.
AB  - This study evaluates and compares the efficacy of the two positions used for
      imaging of the hip in trochanteric fractures. One hundred patients with grade I
      or grade II trochanteric fractures were divided into two equal groups. In group I
      the fracture was reduced and the opposite hip was brought to full abduction,
      neutral flexion and neutral rotation. In group II, the fracture was reduced and
      the opposite hip was flexed beyond 90 degrees, abducted and externally rotated.
      Only patients with minimal or no comminution were included in this study. The
      radiation exposure time was considerably less in group II. The abduction angle
      between the two limbs of the fracture table was higher in group II and it was
      possible to visualize the femoral head completely in the lateral view in 96 per
      cent of patients in group II and 76 per cent in group I. We strongly recommend
      that the opposite hip should be flexed to about 90 degrees, abducted and
      externally rotated if it is not possible to see the femoral head completely in
      the lateral view.

PMID- 7829188
TI  - Locked intramedullary nailing for complex non-union of the tibia.
AB  - Ten patients with complex non-union of the tibia were treated by locked
      intramedullary nailing. These patients had scarred skin as a result of initial
      severe open fractures, multiple debridement or fasciotomies with external
      fixators and skin grafts applied. Seven of the patients also had previous
      osteomyelitis or pin track infections. Fully pain-free walking was achieved in
      all patients and radiological union in nine patients without the need for a bone
      graft. Four patients developed infection after nailing, of which three resolved
      with treatment.

PMID- 7829189
TI  - Diagnostic peritoneal lavage: volume of lavage effluent needed for accurate
      determination of a negative lavage.
AB  - While the ability of diagnostic peritoneal lavage (DPL) to 'rule out' occult
      intra-abdominal injuries has been well established, the volume of lavage effluent
      necessary for accurate prediction of a negative lavage has not been determined.
      To address this, 60 injured adults with blunt (N = 45) or penetrating (N = 15)
      trauma undergoing DPL were evaluated prospectively through protocol. After
      infusion of 1l of Ringer's lactate solution, samples of lavage effluent were
      obtained at 100 cm3, 250 cm3, 500 cm3, and 759 cm3, and when no more effluent
      could be returned (final sample). DPL was considered negative if final sample RBC
      count was < or = 100,000/mm3 for blunt injury and < 50,000/mm3 for penetrating
      injury. The conclusion is that at 100 cm3 of lavage effluent returned, negative
      results are highly predictive of a negative DPL (98 per cent), though 250 cm3 of
      lavage effluent is required to predict a negative DPL uniformly (100 per cent).

PMID- 7829190
TI  - Retrobulbar haemorrhage: can blindness be prevented?
AB  - Retrobulbar haemorrhage is a rare complication following orbital trauma or
      surgery occurring in less than 1 per cent of cases. Early diagnosis and treatment
      of this complication may save the vision of the affected eye. This paper
      illustrates cases where diagnosis was not made and blindness resulted. We also
      present two cases of successful treatment due to early diagnosis.

PMID- 7829191
TI  - Intracapsular fractures of the femoral neck in young patients.
AB  - The details of the aetiology, treatment and outcome of acute intracapsular
      fractures for 58 fractures in 57 patients aged less than 60 years, were
      prospectively studied. The majority of the injuries were sustained by low energy
      trauma. Eighty-four per cent united uneventfully. There was a non-union rate of 7
      per cent, and avascular necrosis rate of 10 per cent. Better results were
      obtained from closed than open reduction. The results do not support the commonly
      held view that this injury carries a poor prognosis in young patients.

PMID- 7829192
TI  - Extradural haematoma following intrauterine trauma.

PMID- 7829193
TI  - Collicular fractures of the medial malleolus.

PMID- 7829194
TI  - Blunt pancreatic transection: management by distal pancreatectomy with splenic
      salvage.

PMID- 7829195
TI  - Three-dimensional CT reconstruction of the scapula in the management of a child
      with a displaced intra-articular fracture of the glenoid.

PMID- 7829196
TI  - False aneurysm of the profunda femoris artery due to malunion of a hip fracture.

PMID- 7829197
TI  - Traumatic rupture of the abdominal wall musculature.

PMID- 7829198
TI  - Delayed diagnosis of septal haematoma and consequent nasal deformity.

PMID- 7829199
TI  - Lightning injury and glioma.

PMID- 7829200
TI  - Pasteurella tenosynovitis following a dog bite.

PMID- 7829201
TI  - The pinless fixator--Part II.

PMID- 7829202
TI  - The pinless external fixator--relevance of experimental results in clinical
      applications.
AB  - The pinless external fixator was intended as a stable, temporary, minimally
      invasive fixator for severe tibial fractures ensuring safer conversion to an
      intramedullary nail. An in vitro study showed that the pinless fixator was
      mechanically not as stiff as the conventional AO tubular device, the main problem
      being low axial stiffness. This study involving initial clinical trials with the
      pinless fixator on tibial fractures in St. Gall is based on the experimental work
      and previous clinical experience of the main author. From June 1992 to June 1994
      10 tibial fractures (eight II degrees and III degrees open, one closed with
      compartment syndrome, one infected non-union) were temporarily stabilized with a
      pinless fixator. In another patient a calcaneal traction device was applied. The
      pinless fixator was applied immediately in eight cases and three times as a
      secondary measure. All patients were scheduled for a secondary change of
      treatment. The tibiae were stabilized with four clamps and one anterior rod. The
      clamps were inserted via transverse stab incisions. Intraoperatively the pinless
      fixator was easy to handle and complications did not occur. Seven different
      surgeons needed an average of 20 minutes for insertion. Postoperative care was
      the same as for conventional fixators. Six patients were treated secondarily with
      an i.m. nail, three with an external fixator on average after 12 days. One
      patient died on day 1. The pinless fixator failed twice in one patient (incorrect
      insertion, fall). Reversible pain in the tendons of the foot extensor muscles was
      noticed. One superficial clamp track infection was seen. All clamps were reused
      more than three times. The pinless fixator is stable enough for temporary
      fracture fixation of the tibia in a four clamp one bar construction. A
      prerequisite for stability is the proper application technique ("grab test",
      rocking movements). Weight-bearing should be limited to a minimum and needs a
      compliant patient. The application technique is easy to learn suggesting that the
      pinless fixator could be an ideal tool for emergency stabilization. The primary
      application of this fixator leaves all further treatment modalities open
      (repeated debridements, evaluation of the open fracture). It may also be of
      particular value to many clinicians working with reamed nails as their only
      secondary treatment option for open tibial fractures.

PMID- 7829203
TI  - Routine application of the pinless external fixator.
AB  - One serious disadvantage of conventional fixator systems is the need to open the
      medullary space, hence creating a direct communication with the exterior. The new
      pinless external fixator does not have this major disadvantage, because the
      fixator clamps simply rest on the cortical bone without penetrating it.
      Clinically, this easily managed system is intended for fractures of the tibia in
      cases in which primary internal fixation is precluded either by precarious local
      or general conditions or by infrastructural problems. In such situations the new
      pinless fixator is an excellent device with which to achieve good stabilization
      of the fracture rapidly, while leaving open all options for subsequent alteration
      of treatment. If the surgeon decides to convert to locked intramedullary nailing,
      the pinless fixator facilitates the new approach, because it can be used as a
      distractor and makes it unnecessary to transfer the patient to a fracture table.

PMID- 7829204
TI  - Application of the pinless external fixator in severely burned patients.
AB  - In the treatment of patients with full thickness burns of the limbs adequate
      positioning is known as a critical condition for a favourable outcome after
      debridement and skin grafting. Up to now prevention of wound compression,
      prevention of shear forces and daily wound inspection were facilitated by using
      halofixators (HF) for the skull and AO external fixation (AO-EF) systems for the
      limbs. For the skull the HF is still the method of choice. However, in burned
      limbs the AO-EF has the considerable disadvantage that the pins penetrate the
      medullary cavity. Pin track infections, which occur quite frequently in burn
      patients, may thus lead to osteitis and additional impairment of the patient's
      compromised immune function. For these reasons, a new pinless fixation system has
      been introduced and tested in a series of eight patients with burns of the lower
      limbs. The special pin clamp system affects only the external subperiosteal
      portion of the bone. Application of the clamps is very fast since no drilling is
      necessary. The advantages of external fixation are retained without the
      associated disadvantages. Clinical examples are presented and discussed.

PMID- 7829205
TI  - Documentation.
AB  - In the period from 1. January to 31. December 1992, the new pinless external
      fixator was applied in eight European and North American clinics as part of a
      prospective multicentric study run by the AO/ASIF Documentation Centre. The aim
      of this study was to determine the indications, handling, and clinical results
      with the new fixator. The new pinless fixator was used 77 times on a total of 75
      patients. The main indications were fresh tibial shaft fractures for which
      immediate definitive treatment was impossible. The majority of cases were
      secondarily stabilized with an unreamed tibial nail once the local and/or general
      condition of the patient had improved. In the remaining cases the pinless fixator
      was used for calcaneal and tibial head traction, segment transport and temporary
      stabilization in cases of tibial infection. Only after long-term application of
      the fixator was local infection at the pin site observed. There were no other
      complications. The new pinless fixator is a valuable addition in the treatment of
      fresh tibial fractures, in particular, in those cases which cannot be primarily
      treated due to contributing factors whether local or general.

PMID- 7829206
TI  - Experience with the pinless fixator in the treatment of fractures of the lower
      leg.
AB  - This is a report of the experience we have gathered in the application of the
      pinless fixator in cases of tibial fracture with soft tissue damage. In the
      Berufsgenossenschaftlichen Unfallklinik Ludwigshafen (Clinic for Trauma Surgery)
      12 diaphyseal fractures of the tibia were stabilized with the pinless fixator in
      1991. In all cases, conversion to an intramedullary nail was intended from the
      very beginning and was performed in 11 cases. In one case, a conventional
      external fixator had to be selected instead. The injuries included first and
      second degree open and closed fractures, mostly from group A of the AO
      classification. At conversion four bacteriological smear tests from the medullary
      cavity proved positive. In four cases, transitory peroneal deficiencies were
      diagnosed. When investigating their cause, it seemed that the present geometry of
      the pinless arms might be responsible for pressure damage to the soft tissues.
      Possibly this difficulty could be solved by altering the configuration of these
      arms. The pinless external fixator has definitely proved its usefulness when
      later conversion to an intramedullary nail is intended since the final fixation
      can be performed with the pinless device still in place.

PMID- 7829207
TI  - Correlation between viral DNA load and serum anti p19 antibody concentration in
      symptomless human T-lymphotropic virus type-I (HTLV-I)-infected individuals.
AB  - In order to determine whether serum anti-human T-cell lymphotropic virus type I
      (HTLV-I) antibody concentration is correlated with cellular viral DNA load, these
      2 biological parameters were established in 22 symptomless HTLV-I carriers. The
      proviral copy (PVC) number was determined through quantificative polymerase chain
      reaction. Specific antibody titers were determined by Western blot with the end
      point dilution method; the quantification of each antibody was performed through
      ScanBlot by determination of the peak height of each Western-blot band. A
      positive correlation was observed between the PVC number and the titer of total
      antibodies. When the association between the peak height of each antibody and the
      PVC number was studied, a significant positive correlation was observed only with
      anti-p 19. Further evaluation through follow-up studies of symptomless HTLV-I
      individuals is needed to clarify the value of anti-HTLV-I antibody titer as a
      predictor of disease progression.

PMID- 7829208
TI  - Cancer risk following primary hemochromatosis: a population-based cohort study in
      Denmark.
AB  - A population-based cohort of 120 Danish men, discharged with a hospital diagnosis
      of primary hemochromatosis from 1977 to 1989, was followed up to 1989 for
      subsequent cancer risk. Nineteen subjects (including 6 with primary liver
      cancers) were excluded from the analysis, either because they died within the
      same month of hemochromatosis diagnosis or because they had cancer prior to
      diagnosis of hemochromatosis. Among the 101 remaining subjects, 4 primary liver
      cancers occurred one year or more after the diagnosis of hemochromatosis, far
      surpassing the expected number based on incidence rates from the Danish
      population (standardized incidence ratio 92.9, 95% confidence interval 25.0 to
      237.9). The excess of liver cancer was associated with cirrhosis and included
      cholangiocarcinoma as well as hepatocellular carcinoma. Significantly elevated
      risks were also observed for non-hepatic cancers (13 cases; SIR 3.5, 95% CI 1.9
      to 6.0), notably esophageal cancer (2 cases; SIR 42.9, 95% CI 4.8 to 154.9) and
      skin melanoma (2 cases; SIR 27.8, 95% CI 3.1 to 100.3). The results of this
      population-based study are in accordance with the hypothesis that patients with
      primary hemochromatosis have a substantial risk of primary liver cancer. Further
      studies of hemochromatosis may be useful in clarifying the relation of non
      hepatic malignancies to body iron stores in the general population.

PMID- 7829209
TI  - Oral contraceptives and breast cancer: a cooperative Italian study.
AB  - The relationship between oral contraceptives (OC) and breast-cancer risk was
      analysed using data from a case-control study conducted between June 1991 and
      February 1994 in 6 Italian centres on 1,991 patients below age 65 with
      histologically confirmed incident breast cancer and 1,899 controls admitted to
      hospital for a wide range of acute, non-neoplastic, non-hormone-related diseases.
      "Ever OC use" was reported by 18% of cases versus 14% of controls, corresponding
      to a multivariate odds ratio (OR) of 1.1 (95%) confidence interval, Cl 0.9 to
      1.4). The ORs were 1.3 for use lasting < 1 year, 1.1 for 1 to 4 years, 0.9 for 5
      to 8 years, and 1.2 for over 8 years. With reference to age at first use, there
      was some indication that the OR was elevated in women who had started use before
      age 30, but not in those starting at a later age. With reference to time since
      last OC use, the OR was above unity for women who had stopped for less than 10
      years (1.6 for 1 to 4 years; 1.7 for 5 to 9 years), but the OR declined to unity
      for women who had stopped OC use for 10 years or longer. The OR for women who had
      stopped OC use for less than 10 years was consistently elevated across strata of
      selected covariates, and was directly related to the duration of use (OR 1.3 for
      < 5 years, 1.7, for > or = 5 years). In contrast, the OR was 0.6, for use lasting
      > or = 5 years in women who had stopped for 10 years or more. The elevated OR for
      women who had recently stopped OC use, together with the absence of association
      (or the suggestion of some protection) for those who had stopped for 10 years or
      more is consistent with the pattern of breast-cancer risk observed after a full
      term pregnancy, and provides important reassurance on a public health level on
      the long-term impact of OCs on breast carcinogenesis.

PMID- 7829210
TI  - Expression of PDGF and PDGF receptors in human astrocytoma operation specimens
      supports the existence of an autocrine loop.
AB  - Established cell lines derived from human malignant astrocytomas typically
      express a combination of platelet-derived growth factor (PDGF) and PDGF receptor
      which could form an autocrine loop. In this study, we screened for the essential
      components of a PDGF autocrine loop in fresh surgical isolates of human
      astrocytomas, using in situ hybridization and immunohistochemical techniques.
      Eight malignant astrocytomas (6 glioblastomas and 2 anaplastic astrocytomas), 5
      low-grade astrocytomas and 4 non-neoplastic glial specimens (mesial temporal
      sclerosis) were evaluated. Malignant astrocytomas, and to a lesser extent low
      grade astrocytomas, expressed more PDGF-A and PDGF-B than non-neoplastic glia.
      PDGF-alpha-receptor expression was elevated both in malignant and in low-grade
      astrocytomas. These data support the argument that PDGF autocrine loops
      contribute to the unregulated growth of human astrocytomas. Expression of PDGF
      and PDGF receptor in low-grade astrocytomas suggests that activation of PDGF
      autocrine loops may be an early event in the pathogenesis of malignant
      astrocytomas.

PMID- 7829211
TI  - Frequent loss of heterozygosity at telomeric loci on 22q in sporadic colorectal
      cancers.
AB  - To date, several tumor-suppressor genes responsible for the tumorigenesis of
      colorectal cancer have been identified. However, studies of loss of
      heterozygosity (LOH) have suggested several chromosomal regions which may contain
      additional tumor-suppressor genes for colorectal cancer. To determine the extent
      and variation of allelic loss on 22q, on which LOH has been frequently observed,
      a total of 68 sporadic colorectal cancers was examined for LOH on the chromosome
      arm by means of 16 polymorphic DNA markers. LOH was observed in 28 tumors (41%),
      of which 9 showed LOH at all informative loci. The remaining 19 tumors showed
      variable patterns of partial loss on 22q, delimiting the smallest region of
      overlap (SRO) between D22S90 and D22S94. Moreover, LOH within the SRO correlated
      with a progression in terms of Dukes' stages. These results suggest that an
      additional tumor-suppressor gene for colorectal cancer may exist on 22q distally
      to the NF2 locus and that inactivation of the gene may possibly play a role in
      the progression or metastasis of colorectal cancers.

PMID- 7829212
TI  - Deletion mapping of the long arm of chromosome 22 in human meningiomas.
AB  - Cytogenetic and molecular genetic analyses have shown that a tumor-suppressor
      gene for human meningioma is located on the long arm of chromosome 22. Recently,
      somatic mutations of the NF2 gene have been identified in sporadic meningiomas.
      However, tumorigenesis of certain cases of meningioma cannot be fully explained
      by inactivation of the NF2 gene alone. Thus, to obtain some indication as to the
      existence of another tumor-suppressor gene, it seemed important to re-examine the
      loss of heterozygosity (LOH) on 22q in sporadic meningioma. A total of 46
      sporadic meningiomas was examined for LOH at 20 loci on 22q. LOH was observed in
      29 tumors (63%), of which 13 (28%) showed different patterns of a partial loss of
      22q. However, the NF2 locus was retained in one tumor that lost a more distal
      part of 22q. Moreover, 27 of the 28 tumors which showed LOH at the NF2 locus also
      lost alleles at more telomeric loci. These results raise the possibility that
      another tumor-suppressor gene for meningioma may exist on 22q and that its
      localization may be distal to the D22S102 locus.

PMID- 7829213
TI  - Cancer risk after renal transplantation in the Nordic countries, 1964-1986.
AB  - The theory that cancer may arise under conditions of reduced immune capacity is
      supported by observations of humans with immune deficiencies such as occur
      following organ transplants. However, no study on humans has been done in which
      the reference population was the same as that in which the cancer cases arose and
      in which there was a sufficiently long period of follow-up. Information on 5,692
      Nordic recipients of renal transplants in 1964-1982 was linked with the national
      cancer registries (1964-1986) and population registries. Person-years at risk
      were calculated from the date of first transplantation until death or the end of
      the study period and were multiplied by the appropriate age- and calender
      specific incidence rates to obtain the expected numbers of cancers. Standardized
      incidence ratios (SIR) were calculated after stratification by a number of
      recorded variables. Altogether, 32,392 person-years were accrued, and 471 cancers
      occurred, yielding overall SIR of 4.6 (95% CI, 4.0 to 5.2) for males and 4.5 (95%
      CI, 4.0 to 5.2) for females. Significant overall 2- to 5-fold excess risks in
      both sexes were seen for cancers of the colon, larynx, lung and bladder, and in
      men also for cancers of the prostate and testis. Notably high risks, 10-fold to
      30-fold above expectation, were associated with cancers of the lip, skin (non
      melanoma), kidney and endocrine glands, also with non-Hodgkin's lymphoma, and in
      women also with cancers of the cervix and vulva-vagina. Among a number of donor
      and recipient variables studied, including tissue types and compatibility (ABO,
      HLA, DR), age below 45 years at the time of transplantation was the most
      important determinant for increased risk at most sites. Kidney transplantation
      increases the risk of cancer in the short and in the long term, consistent with
      the theory that an impaired immune system allows carcinogenic factors to act. The
      tumor risk is small in comparison with the benefits of transplants, but patients
      should be followed up for signs of cancer.

PMID- 7829214
TI  - Smoking and cancer mortality among U.S. veterans: a 26-year follow-up.
AB  - On the 30th anniversary of the U.S. Surgeon General's report Smoking and Health,
      we present updated results from one of the original cohort studies that comprised
      the groundbreaking document. A 26-year follow-up of 248,046 U.S. veterans
      evaluating the risks of cigarette smoking revealed strong dose-response effects
      between smoking and total cancer and a large number of cancer sites. Over 50% of
      cancer deaths among current smokers and 23% of cancer deaths among former smokers
      were attributable to cigarette smoking. These findings further demonstrate the
      large and unique role cigarette smoking plays in cancer etiology and the
      importance of smoking cessation to reduce this enormous public health burden.

PMID- 7829215
TI  - International renal-cell cancer study. I. Tobacco use.
AB  - The relationship between renal-cell cancer (RCC) and tobacco use was investigated
      in an international, multicenter, population-based case-control study.
      Coordinated studies were conducted in Australia, Denmark, Germany, Sweden and the
      United States using a shared protocol and questionnaire. A total of 1,732 cases
      (1,050 men, 682 women) and 2,309 controls (1,429 men, 880 women) were interviewed
      for the study. No association was observed between risk and use of cigars, pipes
      or smokeless tobacco. A statistically significant association was observed for
      cigarette smoking, with current smokers having a 40% increase in risk [relative
      risk (RR) = 1.4, 95% confidence interval (CI) 1.2-1.7]. Risk increased with
      intensity (number of cigarettes) and duration (years smoked). Among current
      smokers the RR for pack-years rose from 1.1 (95% CI 0.8-1.5) for < 15.9 pack
      years to 2.0 (95% CI 1.6-2.7) for > 42 pack years (p for trend < 0.001). Long
      term quitters (> 15 years) experienced a reduction in risk of about 15-25%
      relative to current smokers. Those who started smoking late (> 24 years of age)
      had about two-thirds the risk of those who started young (< or = 12 years of
      age). Overall, the findings of this pooled analysis confirm that cigarette
      smoking is a causal factor in the etiology of RCC.

PMID- 7829216
TI  - Clinical validation of the new ELSA-CA 125 II assay: report of a European
      multicentre evaluation.
AB  - The ELSA-CA 125 II is a second-generation radioimmunoassay for the quantification
      of CA 125 in serum. In a multicentre study involving 49 follow-ups of patients
      with ovarian cancers, and 880 other patients, 2.8% of healthy persons, 25% of 149
      patients with benign gynaecological diseases and 39% of 82 patients with benign
      non-gynaecological diseases had CA 125 levels above 35 U/ml. Using the 35 U/ml
      cut-off, sensitivities among epithelial ovarian cancers were found to be 85% in
      serous tumors, 41% in mucinous tumors and 83% in other types. During follow-up of
      patients with serous ovarian cancers, we observed an equivalent behaviour of both
      assays--first- and second-generation--with the clinical evolution. We also
      compared results obtained with other assays commercially available; these were
      significantly different when a polyclonal antibody was used in the sandwich
      assay.

PMID- 7829217
TI  - Effects of cytokine-mediated modulation of nm23 expression on the invasion and
      metastatic behavior of B16F10 melanoma cells.
AB  - The molecular mechanisms of tumor invasion and metastasis are yet to be fully
      elucidated. A potential tumor-metastasis-suppressor gene nm23 has been described
      in certain rodent and human tumors. In the present study, we examined the
      potential anti-invasive and anti-metastatic effect of nm23 gene in B16F10 cells,
      a malignant murine melanoma cell line. Transfection of nm23 gene into B16F10
      melanoma cells resulted in significant suppression of the invasiveness and
      metastatic ability of melanoma cells and significantly enhanced the survival of
      tumor-bearing mice. B16F10 melanoma cells transfected with nm23 produced
      significantly less soluble ICAM-I and were more susceptible to LAK-cell-mediated
      cytotoxicity. Co-culture of B16F10 melanoma cells with IL-2 had no effect on nm23
      expression, whereas treatment with PGE2, TNF-alpha and IFN-gamma resulted in down
      regulation of nm23 expression. Concomitantly, in vivo treatment with TNF-alpha or
      IFN-gamma in experimental mice increased pulmonary metastases and lowered the
      overall survival period, as compared with IL-2 treatment alone. These results
      provide evidence that nm23, in addition to its anti-metastatic function, could
      also be involved in modulating tumor-target-structure expression, in down
      regulating invasive potential and in production of soluble intracellular adhesion
      molecules. The down-regulation of nm23 by TNF-alpha, IFN-gamma and particularly
      by PGE2 warrants re-examination of current immunotherapeutic protocols and of the
      role played by PGE2 in tumor progression.

PMID- 7829218
TI  - Mitoxantrone treatment of murine myeloid leukaemia sublines.
AB  - The low-cell-dose (LD) and the high-cell-dose (HD) transplant variants of the SA7
      murine myeloid leukaemia cell line have different growth characteristics and
      clinical presentations. In addition, the low-cell-dose transplant subline (SA7LD)
      was more responsive than the high-cell-dose variant (SA7HD) to mitoxantrone
      treatment in vivo. Bone-marrow cells of mice cured of SA7LD leukaemia, as well as
      bone-marrow cells of normal mice treated with priming doses of mitoxantrone in
      vivo became significantly (p = 0.012) less sensitive to subsequent treatment with
      mitoxantrone in vitro. This effect was detected by both the colony assay and the
      tritiated thymidine uptake assay. There appears to be a correlation between the
      ability of normal bone-marrow cells present in leukaemic mice to develop this
      protective effect and their ability to survive chemotherapy with mitoxantrone.
      The protective effect was "lost" by bone-marrow cells of mice dying while in
      remission. Doses of mitoxantrone that resulted in the loss of protective effect
      by bone-marrow cells of normal mice were found to be fatal to SA7HD leukaemia
      bearing mice. However, these doses were not toxic to normal mice.

PMID- 7829219
TI  - Mitogenic effect of the 15-kDa gross cystic disease fluid protein (GCDFP-15) on
      breast-cancer cell lines and on immortal mammary cells.
AB  - The biological significance of a major protein component in the fluid of gross
      cystic breast disease and a recognized marker of apocrine metaplasia, i.e. the 15
      kDa glycoprotein (GCDFP-15), is presently unknown. We have added GCDFP-15 to cell
      culture medium and tested its effect on proliferation of 4 human breast-cancer
      cell lines (MCF7, BT474, MDA-MB231 and T47D) and a "normal" human immortal breast
      cell line (MCF10A). These breast-cell lines showed a mitogenic response to GCDFP
      15 (10 micrograms/ml). GCDFP-15 enhanced cell growth of the MCF10A, MCF7, BT474
      and MDA-MB231 cell lines at both 48 and 96 hr of exposure. The glycoprotein
      exerted a mitogenic effect on the T47D cell line at 48 hr but not at 96 hr. This
      may be due to an auto-regulatory effect of endogenous GCDFP-15 synthesized by the
      T47D cells. GCDFP-15 was ineffective on 2 colon-cancer cell lines (HT29 and NIC
      H716), on the IMR32 neuroblastoma cell line and on the NIC-H209 small-cell lung
      carcinoma cells. A separate major breast cystic disease fluid protein of 24 kDa
      (GCDFP-24) was tested, following the same experimental design, on the 5 breast
      cell lines, and showed no mitogenic activity. The mitogenic effect of GCDFP-15
      observed in this study in both "normal" and malignant breast epithelial cells
      suggests a possible relationship between apocrine metaplasia in breast cystic
      disease and the development of breast epithelial hyperplasia. In addition, a
      possible role of GCDFP-15 in breast-cancer progression should be considered.

PMID- 7829220
TI  - IFN-alpha 1 gene transfection completely abolishes the tumorigenicity of murine
      B16 melanoma cells in allogeneic DBA/2 mice and decreases their tumorigenicity in
      syngeneic C57BL/6 mice.
AB  - The murine B16 melanoma (H-2b) was transfected with a retroviral vector
      containing the mouse IFN-alpha 1 gene. IFN-alpha 1-transfected cells produced IFN
      alpha in vitro and exhibited an altered phenotype characterized by a decreased
      rate of multiplication, enhanced expression of H-2 antigens, an antiviral state
      to VSV, and decreased pigmentation. Control and IFN-alpha 1-transfected cells
      were tested for their ability to grow in syngeneic (H-2b) C57Bl/6 and allogeneic
      (H-2d) DBA/2 mice. IFN-alpha 1-producing B16 clones were less tumorigenic after
      s.c., i.p., and i.v. routes of injection than IFN-non-producer B16 clones in
      syngeneic C57Bl/6 mice. IFN-alpha 1-producing B16 cells were, however, totally
      rejected by allogeneic DBA/2 mice regardless of the routes and inocula tested,
      while control B16 cells grew in and killed DBA/2 mice. The total rejection of IFN
      alpha 1-transfected B16 cells in allogeneic mice appeared to be dependent on T
      cells as these cells grew in DBA/2 nude mice. Incubation of IFN-alpha-producing
      clones with anti-mouse IFN-alpha/beta prior to injection into C57Bl/6 mice did
      not enhance their tumorigenicity. Likewise, injection of C57Bl/6 and DBA/2 mice
      with antibody to IFN-alpha/beta did not enhance the tumorigenicity of IFN-alpha 1
      transfected cells. C57Bl/6 mice immunized with irradiated IFN-alpha 1 cells were
      only slightly protected against a subsequent challenge with parental B16 cells.
      In contrast, DBA/2 mice immunized with irradiated IFN-alpha 1 cells exhibited
      tumor-specific, long-lasting immunity to subsequent challenge with parental B16
      cells.

PMID- 7829221
TI  - Relationship between stages of mammary development and sensitivity to gamma-ray
      irradiation in mammary tumorigenesis in rats.
AB  - Mature Wistar-MS rats were ovariectomized and treated with estradiol benzoate
      and/or progesterone. Control animals were treated with olive oil. The rats were
      then exposed to gamma-rays and implanted with a pellet of diethylstilbestrol. The
      incidence of mammary tumors in rats treated with estradiol benzoate or with
      progesterone was significantly higher than in rats in the non-treated control
      group, whereas, in rats treated with both estradiol benzoate and progesterone,
      the incidence was not significantly different from that in the controls.
      Histological examination of the mammary tumors showed 2 types of neoplasm:
      adenocarcinoma and fibroadenoma. Interestingly, over half of all the tumors in
      the rats treated with estradiol benzoate were adenocarcinomas, while
      fibroadenomas were mainly induced in the rats treated with progesterone or with
      both estradiol benzoate and progesterone. The expression of estrogen and
      progesterone receptors in the tumor tissues showed some differences according to
      whether the groups were treated with estradiol benzoate or with progesterone.
      Morphologically, mammary glands at irradiation showed well-developed
      lobuloalveoli in both the estradiol-benzoate-treated rats and in those rats
      treated with both estradiol benzoate and progesterone. This was consistent with
      the higher incorporation of [3H]thymidine into the DNA in the mammary glands of
      rats in both of these groups. Our findings suggest that a more advanced
      developmental stage of the mammary glands, dependent upon ovarian hormones, is
      related to a higher incidence of mammary tumors induced by irradiation.

PMID- 7829222
TI  - Modulation of cellular chemoresistance in keratinocytes by activation of
      different oncogenes.
AB  - Response to chemotherapeutic agents in malignant tumors depends on many factors,
      most of which are as yet unknown. We investigated the correlation between the
      activation of different oncogenes and protein-kinase-C (PKC) modulation, and the
      cytotoxicity of some of the most widely used anti-cancer drugs. We transformed
      the murine keratinocyte cell line PAM 212, with different oncogenes (v-H-ras, v
      myc and adenovirus E1a) and a mutant p53 suppressor gene (mp53). The cytotoxic
      effect of cisplatin (CDDP), doxorubicin (DOX) and vincristine (VCR), together
      with the concomitant action of modulators of PKC, TPA and staurosporine were
      evaluated by the crystal-violet method, thymidine incorporation and flow
      cytometry. We report that (a) the oncogene v-H-ras induces resistance to CDDP (>
      50%), DOX (> 25%) and VCR (> 20%); (b) the E1a oncogene induces only resistance
      to VCR (> 40%) and marked sensitivity to CDDP and DOX; (c) the mp53 oncogene
      induces more resistance to VCR and insignificant resistance to the other drugs;
      and (d) activation of PKC by TPA increases the resistance to VCR and DOX in cells
      transformed by the v-H-ras, while it significantly increases the lethality with
      CDDP of the E1a-transformed cells. Staurosporine increases the cytoxicity of all
      the drugs, especially in the E1a-transformed keratinocytes. In the flow-cytometry
      analysis, the percentage of BUdR incorporation was related to sensitivity to anti
      cancer drugs.

PMID- 7829223
TI  - Loss of chromosome 3p arm differentiating tumorigenic from non-tumorigenic cells
      derived from the same SV40-transformed human mammary epithelial cells.
AB  - After immortalization of human normal mammary epithelial cells by replication
      defective SV40 genome integration, 2 cultures were developed independently. Both
      had the same integration site, in band 9q21, but rapidly diverged karyotypically.
      After a few passages, one, designated SC2T2, exhibited near-diploid (a) and the
      other, designated SL2T2, near-tetraploid (b) karyotypes. The simplest formulas
      were 44, X, -X, der(3;22) (q10;q10), der(4) t(4;9)(q34;q12), +8, +9, add(13)(p1),
      der(19) t(8;19)(q21;p13.3), add(22)(p1) for karyotype (a) and 93, XXXX,
      add(1)(q12), add(11)(q13), +20 for karyotype (b). A number of alterations were
      further acquired with passages. Both cell cultures were tumorigenic, but their
      efficiency of grafting in nude mice largely differed: it was low for SL2T2 and
      high for SC2T2 cultures. All cultures of the xenografted tumors, obtained from
      either SL2T2 or SC2T2, exhibited the same clonal anomalies as those
      characterizing karyotype (a). It was concluded that only cells with karyotype (a)
      were tumorigenic, and that the difference in the tumorigenic potential of
      cultures SC2T2 and SL2T2 was related to their richness in cells with this
      karyotype. The comparison of the various karyotypes, together with data obtained
      in other cell types transformed by SV40, suggests that the acquisition of
      tumorigenicity in S2T2 mammary epithelial cells may be related to the loss of
      chromosome 3p arm.

PMID- 7829224
TI  - Tumor resistance to oxidative stress: association with ras oncogene expression
      and reversal by lovastatin, an inhibitor of p21ras isoprenylation.
AB  - The ras oncogene family has been implicated in tumor resistance to ionizing
      radiotherapy. Using the gene-transfer model, we show here that ras expression may
      also affect cell responses to chemical inducers of oxidative stress. Studies
      involving human osteosarcoma subclones, which vary in their levels of EJras
      expression, revealed a tight correlation between the amounts of ras-encoded mRNA
      and p21 produced, and the degree of resistance to doxorubicin or hydrogen
      peroxide. Differences in response could not be explained by increased activity of
      anti-oxidant enzymes such as superoxide dismutase, glutathione reductase,
      glutathione S-transferase or glutathione peroxidase. Moreover, there were no
      significant differences in glutathione levels. Although the resistant cells had
      elevated levels of gamma-glutamyl-transferase mRNA indicative of an increased
      rate of glutathione turnover, this elevation was not specific for ras-transfected
      cell lines. Lovastatin, an inhibitor of protein isoprenylation critical for
      p21ras membrane association and function, restored the sensitivity of ras
      transformed cells to doxorubicin and hydrogen peroxide. The data indicate that
      pharmacological agents affecting ras expression may enhance responses of some
      human tumors to free-radical-mediated chemotherapies.

PMID- 7829225
TI  - Reduction of translation initiation factor 4E decreases the malignancy of ras
      transformed cloned rat embryo fibroblasts.
AB  - Expression of the T24ras oncogene induces malignancy (tumor growth, invasion and
      metastasis) in cloned rat embryo fibroblasts (CREF T24). In CREF T24, the rate of
      phosphorylation of eukaryotic translation initiation factor 4E (eIF-4E) is
      increased, resulting in increased protein synthesis rates. We have recently shown
      that reducing the protein levels of eIF-4E in CREF T24 (AS4E line) markedly
      decreases soft-agar colonization, increases tumor latency periods and increases
      tumor doubling times without significantly altering monolayer growth. In this
      study, cells with reduced eIF-4E had delayed and reduced invasiveness and
      decreased experimental metastasis. Furthermore, reduced eIF-4E levels correlated
      with decreased expression of the metastasis-associated 92-kDa collagenase type-IV
      and exon-6 variants of the CD44 adhesion molecule [CD44(6v)]. Reduced eIF-4E
      levels correlated inversely with increased levels of the putative metastasis
      suppressor protein nm23. Cell lines established from AS4E tumors and lung
      metastases exhibited increased levels of eIF-4E protein and protein synthesis
      rates compared to the AS4E line. Tumor-derived AS4E had the shortened tumor
      latency periods of CREF T24 but displayed the slow tumor-growth rates of AS4E.
      Tumor-derived AS4E exhibited the metastatic capacity of CREF T24 controls.
      Furthermore, tumor- and lung-nodule-derived AS4E expressed levels of CD44 (6v)
      and the 92-kDa collagenase type IV comparable to CREF T24 and displayed reduced
      levels of nm23 relative to AS4E. These results demonstrate that eIF-4E is an
      important effector molecule involved in oncogenic p21ras-induced malignant
      transformation.

PMID- 7829226
TI  - Reduction of tumour intracellular pH and enhancement of melphalan cytotoxicity by
      the ionophore Nigericin.
AB  - Nigericin is an ionophore which permits the influx of H+ ions into cells down a
      concentration gradient, thus reducing intracellular pH (pHi) when extracellular
      pH is low. The effects of nigericin on the pHi of solid murine tumours in vivo
      were examined using 31P magnetic resonance spectroscopy. Nigericin at 2.5 mg/kg
      i.p. reduced pHi by 0.2-0.3 pH unit in the KHT and RIF-I tumours but had no
      effect on pHi in the SCCVII/Ha tumour. In vitro studies have shown that reduced
      pH can increase the toxicity of melphalan. Therefore, the anti-tumour effect of
      combining nigericin with melphalan was also examined. Nigericin at 2.5 mg/kg i.p.
      given before various doses of melphalan resulted in substantial delay in growth
      of the RIF-I tumour over that induced by melphalan alone. This observation was
      confirmed by an in vivo/in vitro excision assay, where nigericin given before
      melphalan produced a 30-fold increase in cell killing. By contrast, no
      enhancement of melphalan-induced cell killing by nigericin was observed in the
      KHT and SCCVII/Ha tumours, using growth delay and in vivo/in vitro excision
      assays, respectively.

PMID- 7829227
TI  - Growth properties of a human melanoma cell line are altered by adeno-associated
      parvovirus type 2.
AB  - The adeno-associated parvoviruses (AAV) are known for their oncosuppressive
      activity. This report shows that infection of the human melanoma cell line MKr
      with AAV-2 leads to chromosomal integration of the viral DNA. The resulting
      cultures show decrease of saturation density and reduction in their ability to
      form colonies from single cells and thus to resemble normal cells. After single
      cell cloning they may give rise to growth-arrested, terminally differentiating
      large, multinucleated cells with dendrite-like extensions, large nucleoli and the
      ability to synthesize melanin pigment. In cultured melanoma cells, melanin
      synthesis is correlated with cellular senescence, and since senescent cells cease
      to proliferate and withdraw from the cell cycle, the apparent induction of growth
      arrest and terminal differentiation in malignant cells by AAV may provide one
      explanation for the anti-neoplastic activity of these viruses.

PMID- 7829228
TI  - Down-regulation of collagen XII in transformed mesenchymal cells.
AB  - Collagen XII is a complex multidomain protein associated with the surface of
      interstitial collagen fibrils. This protein is produced in large amounts by
      fibroblasts cultivated in vitro. However, it is completely absent from cells
      transformed by the oncogene v-myc or v-src and from cells derived from a
      methylcholanthrene-induced fibrosarcoma. Since all these cells lack any mRNA for
      collagen, XII, it seems likely that the synthesis is blocked at the
      transcriptional level. Experiments with a temperature-sensitive mutant of Rous
      sarcoma virus demonstrated that a single oncogene product is sufficient to
      inhibit the synthesis. A reduction in the expression of collagen XII might have
      profound effects on the stability of the extracellular matrix of transformed
      cells.

PMID- 7829229
TI  - Experimental local therapy of human melanoma with lytic magainin peptides.
AB  - Magainin peptides and model amphipathic peptides exhibit antibiotic activity and
      are also cytolytic for transformed human cells. Here we demonstrate in vitro that
      MSI-511 (an all-D amino-acid model magainin peptide) and MSI-130 (a margainin
      analogue) were more lytic for 17 human melanomas than for normal melanocytes.
      Melanomas established s.c. in athymic nude mice and then injected once with the
      peptide MSI-511 completely disappeared in 6 out of 9 animals, whereas a control
      peptide had no effect. Murine skin at the tumor injection site was initially
      affected, but healed within 2 weeks with minimal scarring. Similarly, accelerated
      healing was seen in human skin grafted to SCID mice and injected with MSI-511.
      Our results indicate that lytic magainin peptides can be used for local tumor
      therapy with minimal long-term damage to normal tissues.

PMID- 7829230
TI  - Evidence for sexual transmission of HTLV-II in Spain.

PMID- 7829231
TI  - Screening for breast cancer in pre-menopausal women. Who should decide?
AB  - The recent UICC meeting on breast cancer screening in pre-menopausal women showed
      that experts disagree: some would recommend that screening begin at age 40,
      others would postpone it until after age 50 (Eckhardt et al., 1994). There is
      full consensus that screening at ages 40 to 49 may detect a substantial fraction
      of breast-cancer cases before their clinical manifestation, but the trials
      carried out have not indicated a significant reduction in subsequent mortality.
      As stated in the report of the UICC meeting, "this issue is too large for it to
      remain only the concern of experts." In our opinion, women should be provided
      with full information to enable them to decide themselves what is better for
      them. This means that the available scientific evidence both on benefits and on
      risks should be made quantitatively explicit. As recently reviewed by Hurley and
      Kaldor (1992), potential benefits include saved lives, increased use of
      conservative therapies, and reassurance of women without pre-clinical cancer;
      risks include radiation-induced breast cancer, unnecessary investigations for
      false positives, useless early diagnosis and treatment, diagnosis and treatment
      of lesions not requiring treatment (over-diagnosis), false reassurance, and
      psychological and social morbidity such as anxiety and the stigmatization of
      women with positive diagnosis.

PMID- 7829232
TI  - Lung adenocarcinoma and indicators of asbestos exposure.
AB  - A case-control study was carried out on 145 male lung-cancer patients diagnosed
      at autopsy and 178 controls, in order to investigate the relationship between
      asbestos exposure and the cell type of pulmonary carcinoma. Adenocarcinomas (AD)
      were individually matched with other cell types and with controls. The relative
      risk (RR) of developing AD in relation with lung asbestos body (AB) content as
      the exposure indicator was calculated by using logistic-regression analysis for
      matched sets. Two cutoff levels, 1,000 and 10,000 asbestos bodies per gram dry
      weight (AB/gdw), were used in the analysis. In addition, AB counts were treated
      as a continuous variable (log AB+I). A significant association was found between
      AD and asbestos exposure, using levels and logarithmic transformation. However,
      an association of asbestos exposure with cell types other than AD could not be
      ruled out.

PMID- 7829233
TI  - Circulating gangliosides of breast-cancer patients.
AB  - Gangliosides were isolated from the sera of recently diagnosed breast-cancer
      patients and from individuals who were apparently free of disease. Quantificative
      and qualitative analyses were carried out by 2-dimensional high-performance thin
      layer chromatography and gas chromatography. The locations of isolated
      gangliosides on thin-layer chromatograms were determined by visualization with
      resorcinol, and each spot was quantified by digital image densitometry. The
      ganglioside profiles of cancer patients were compared to those of the control
      group, revealing a significant increase in total lipid-bound sialic acid and a
      specific increase in polysialogangliosides in the patients with breast cancer.
      Furthermore, an increase was noted in the ratio of gangliosides of the b-series
      biosynthetic pathway over those of the a-series in the cancer sera, as compared
      to the controls. Gas chromatographic analysis of the peracetylated methanolysis
      mixtures derived from the total ganglioside fraction of cancer patients supported
      the HPTLC data, with an increase in total sialic acid, galactose, and sphingosine
      residues. No unusual gangliosides were found in the mixture from breast-cancer
      patients.

PMID- 7829234
TI  - Effects of granulocyte-monocyte colony-stimulating factor (GM-CSF) on expression
      of adhesion molecules and production of cytokines in blood monocytes and ovarian
      cancer-associated macrophages.
AB  - The present study was aimed at characterizing the effects of in vitro exposure to
      GM-CSF on blood monocytes and tumor-associated macrophages (TAM) in human ovarian
      cancer. Purified populations of TAM from ovarian cancer patients were studied in
      terms of expression of surface molecules, cytokine production and tumor
      cytotoxicity after overnight incubation with GM-CSF or IFN gamma and LPS, used as
      reference activators. GM-CSF augmented the surface expression of ICAM-I and CD18
      in TAM and in blood monocytes. Stimulation was more prominent in monocytes than
      in TAM, which showed higher baseline expression of this adhesion molecule. ICAM-3
      was not influenced by GM-CSF or by IFN gamma/LPS. GM-CSF-augmented ICAM-I
      expression was associated with higher levels of mRNA transcripts. The protein
      synthesis inhibitor cycloheximide super-induced basal and GM-CSF-induced ICAM-I
      transcripts, thus excluding a role for secondary polypeptide mediators. In the
      absence of stimuli, TAM produced higher levels, compared to monocytes, of IL-6
      and IL-8 but not of IL-1 and TNF. GM-CSF augmented the production of IL-6 and IL
      8 (but not that of IL-1 and TNF) in TAM, whereas it had little effect on blood
      monocyte. Tumoricidal activity was tested against two ovarian tumor cell lines
      (OVCAR3 and SW626). GM-CSF more prominently augmented monocyte cytotoxicity,
      while only 2 of 6 TAM preparations were stimulated by GM-CSF. These results
      suggest that GM-CSF selectively regulates the function of blood monocytes and
      TAM, the effect of this cytokine varying with the parameter and cell population
      examined. These data provide a rational and biological endpoint for further
      studies with GM-CSF as an activator of mononuclear phagocyte function in ovarian
      cancer.

PMID- 7829235
TI  - Regional variations of urokinase-type plasminogen activator in human colorectal
      cancer: a quantitative study by image analysis.
AB  - Qualitative histological studies in the distribution of urokinase-type
      plasminogen activator (uPA) in human colorectal carcinomas have been well
      documented. However, to our knowledge the histological distribution of this
      enzyme has not been quantified in any tumour. For the present image analysis
      study, uPA was demonstrated in sections of human colorectal cancer using
      immunoperoxidase technique. A total of 9 colorectal carcinoma cases were used, in
      which 132 regions were analysed. Within each region, staining intensity
      measurements were made at evenly spaced intervals. Samples of normal mucosa from
      6 cases were also studied. Enzyme levels were assessed with staining intensity
      measurements. For each section, a negative control section was included, in which
      the primary antibody was omitted. Staining for uPA was quantified for each region
      in the test section, and the measurement for the corresponding region of the
      negative control was then subtracted. The enzyme uPA was localised more at the
      tumour edge than in the tumour centre or distant host tissue. These differences
      were highly significant (p < 0.0001). There was also a highly significant
      difference in staining intensity when tumour regions adjacent to pushing edge
      were compared with those adjacent to infiltrating edge (p < 0.0001). Infiltrating
      tumours showed stronger staining for uPA than tumours with pushing edges. Since
      invasive activity is thought to be maximal at the edge of the tumour,
      localisation of uPA at this site is consistent with the role of this enzyme in
      the process of tumour invasion.

PMID- 7829236
TI  - Epstein-Barr virus is localized in the tumour cells of nasal lymphomas of NK, T
      or B cell type.
AB  - Seven cases of nasal lymphoma were studied to identify the lineage of Epstein
      Barr virus (EBV)+ cells using dual-labelling methods. Five cases were
      phenotypically and genotypically of natural killer cell (NK) type with germ-line
      configuration of T-cell receptor (TcR) beta-chain gene and immunoglobulin heavy
      chain joining region (IgJH) gene, with one case each of T- and B-cell type
      showing rearranged TcR beta or IgJH and lambda-light chain genes respectively.
      EBV genome was clonal in all these cases except in the B-cell case where its
      clonality was undeterminable. Using in situ hybridization (ISH) for EBV-encoded
      small nuclear RNA 1 and 2 (EBER), signal was detected in 45% to 88% of nucleated
      cells in the tumours. Immunostaining for EBV latent membrane protein-I (LMP) also
      revealed numerous LMP+ cells in 3/5 NK-type cases and the T- and B-cell cases.
      Using ISH for EBER combined with immunostaining for CD markers and double
      immunohistochemistry for LMP and CD markers, the predominant lineage of the EBV+
      cells was identified as: CD2+CD3-CD19-CD20- CD45R0 +/- CD56+CD68- in the NK-type
      cases, CD2+CD3 +/- CD19-CD20- CD45R0+CD56-CD68- in the T-cell case and
      CD20+CD45R0-CD68- in the B-cell case, in agreement with the genotype and
      phenotype of each tumour. These results show that, in EBV+ nasal lymphomas of NK,
      T- or B-cell lineage, EBV was consistently associated with the tumour-cell
      population and support the view that EBV serves a promoting role in the
      pathogenesis of different types of EBV+ nasal lymphoma.

PMID- 7829237
TI  - Reproductive factors and the risk of renal cell cancer among women.
AB  - In etiologic studies of renal cell carcinoma the role of reproductive variables
      and the use of exogenous hormones have not been well examined. In a population
      based case-control study including 165 female cases and 227 controls, we assessed
      the risk of renal cell cancer associated with reproductive factors and use of
      oral contraceptives and menopausal hormones. Odds ratios were computed using
      logistic regression analyses. Risk was positively associated with number of
      births and inversely associated with age at first birth, with the largest
      increases in risk (more than 2-fold) among women with 5 or more births after age
      25. After adjustment for age, smoking status, body mass index and age at first
      birth, women with 5 or more births had a 2-fold risk (OR = 2.2, 95% CI = 1.2-4.0)
      relative to those with 1 or 2 births. Age at first birth, however, was no longer
      a risk factor when the number of births was adjusted for. The association with
      parity was considerably stronger among women with a history of hypertension or
      above-median body mass index than among those without these conditions. In
      addition, risk was reduced among long-term oral contraceptive users but elevated
      among women who had had a hysterectomy or used menopausal hormones. Our findings
      suggest that reproductive factors, particularly the number of births, may play an
      etiologic role in renal cell cancer among women and deserve further study.

PMID- 7829238
TI  - Modulation of E-cadherin expression and morphological phenotype in the
      intravascular component of adenocarcinomas.
AB  - E-cadherin is a morphoregulatory epithelial cell/cell adhesion molecule whose
      loss from carcinomas probably contributes to a more invasive tumour phenotype.
      Employing an immunohistochemical technique on 25 adenocarcinomas (8 from stomach,
      10 breast, 7 colon) we compared E-cadherin expression and tumour morphology of
      carcinoma that had invaded vascular spaces with that of extravascular carcinoma,
      both in primary tumours and in their lymph node metastases. In 40% of cases
      either at the primary site, in the lymph node metastasis or at both sites, E
      cadherin levels were higher in the often tiny intravascular tumour compartment
      than in the adjacent and much larger extravascular tumour compartment. In no
      tumour was the highest area of E-cadherin expression present within the
      extravascular compartment. Increases in the differentiation and cohesion of
      intravascular tumour occurred in 16% and 20% of cases, respectively. In 3 of 4
      cases showing increased differentiation, but in only 1 of 5 cases showing
      increased cohesion, these morphological changes were associated with increased
      intravascular E-cadherin levels.

PMID- 7829239
TI  - Cancer in patients with ulcerative colitis.
AB  - A cohort of 5,546 ulcerative colitis patients was identified from the Danish
      Hospital Discharge Register for 1977-1989. Patients not included in the cohort
      comprised those with proctitis, those treated in outpatient clinics and those for
      whom follow-up was less than 1 year. The cohort was linked to the Danish Cancer
      Registry in order to assess the risks for colorectal and other cancers. The
      linkage revealed a significant increase in the number of colorectal cancers over
      that in the general population (RR = 1.8; n = 42; 95% CI = 1.3-2.4) with
      consistent relative risks during early and late follow-up. The relative risk was
      considerably higher among younger (20-39 years: RR = 22; n = 8; 95% CI = 9.7-44)
      than older patients (> or = 60 years: RR = 1.3; n = 25; 95% CI = 0.8-1.9), but
      the risk difference between patients and the general population was approximately
      constant across all ages. In addition, we observed a significant increase in the
      relative risk of hepatobiliary cancers (RR = 2.3; n = 9; 95% = 1.0-4.3) and a
      slight but significant increase in the relative risk of non-melanoma skin cancer
      (RR = 1.4; n = 37; 95% CI = 1.0-1.9). In summary, our population-based study
      confirms the increased risk of colorectal cancer among patients with ulcerative
      colitis and provides new leads suggesting that hepatobiliary cancer and non
      melanoma skin cancer should be considered as possible sites for future patient
      monitoring.

PMID- 7829240
TI  - Human high molecular weight-melanoma associated antigen mimicry by mouse anti
      idiotypic MAb MK2-23. Immunohistochemical analysis of the reactivity of anti-anti
      idiotypic MAb with surgically removed melanoma lesions.
AB  - The mouse anti-id MAb MK2-23 bears the internal image of the antigenic
      determinant defined by anti-HMW-MAA MAb 763.74. Active specific immunotherapy
      with anti-id MAb MK2-23 is associated with a statistically significant
      prolongation of survival in patients with malignant melanoma. Characterization of
      the immune response elicited by anti-id MAb MK2-23 may contribute to our
      understanding of the mechanisms underlying the apparent beneficial clinical
      effects of active specific immunotherapy with anti-id MAb MK2-23. Therefore, 8
      HMW-MAA binding anti-anti-id MAbs elicited with MAb MK2-23 were characterized in
      their reactivity with a large panel of surgically removed benign and malignant
      tumors and of normal tissues. The 8 anti-anti-id MAbs displayed subtle
      differences in their immunoperoxidase staining of both benign and malignant
      lesions and of normal tissues. The diversity in the fine specificity of the 8
      anti-anti-id MAbs is likely to reflect the few somatic mutations which occur in
      the amino-acid sequence of the variable regions of their heavy and light chains
      in the course of the immune response to MAb MK2-23. The reactivity patterns of
      the 8 anti-anti-id MAbs with the tissue substrates are similar, although not
      superimposable upon that of anti-HMW-MAA MAb 763.74 elicited with melanoma cells.
      This difference may reflect the imperfect mimicry by anti-id MAb MK2-23 of the
      antigenic determinant defined by anti-HMW-MAA MAb 763.74.

PMID- 7829241
TI  - Multiple births, sex of children and subsequent breast-cancer risk for the
      mothers: a prospective study in Norway.
AB  - Endocrinological changes occurring during pregnancy may influence the subsequent
      cancer risk of the mother. Further, the endocrinological milieu may differ
      according to different birth characteristics. In the present study possible
      relations between multiple births, sex of children and breast-cancer risk were
      examined in a population-based, prospective study of 802,269 parous Norwegian
      women aged 20-56 years. A total of 4,782 women were diagnosed with breast cancer
      during follow-up. Of these, 97 had ever experienced a multiple birth. We found a
      slightly lower risk of breast cancer among women ever having had a multiple birth
      than among women with singletons only (IRR = 0.89, 95% CI = 0.73-1.09). The
      reduction in risk was mainly observed among women with a multiple last birth.
      Further, the reduction in risk seemed to diminish with increasing parity, and
      among women with 4 or more full-term pregnancies, ever having had a multiple
      birth was associated with an elevated risk (IRR = 1.48, 95% CI = 0.97-2.25). The
      sex of the first or last child did not affect the subsequent breast-cancer risk.
      Further, we found no associations with the sex distribution among all children or
      in multiple births, despite a tendency toward a reduced risk among women with
      several daughters only.

PMID- 7829242
TI  - International renal-cell cancer study. II. Analgesics.
AB  - There has been concern about the role of analgesics in the development of renal
      cell cancer, although a few studies have reported moderately elevated risks with
      regular or long-term use. In a large international case-control study of renal
      cell cancer we examined, among other hypotheses, the effect of phenacetin
      containing and of other types of analgesics: paracetamol (acetaminophen),
      salicylates (mainly aspirin) and pyrazolones (e.g., antipyrine or phenazone).
      Relative risks, adjusted for the effects of age, sex, body-mass index, tobacco
      smoking and study centre, were not significantly increased with intake of
      phenacetin, either when lifetime consumption was categorized at the level of > or
      = 0.1 kg or when subjects were subdivided further by amount. Nor were
      paracetamol, salicylates or pyrazolones linked with renal-cell cancer. No
      consistently increasing risks with consumption level was found. The lack of
      association was not altered by restricting analgesic use to that which occurred 5
      or 10 years before the defined "cut-off" date or when analysis was restricted to
      exclusive users of a particular type of analgesic. Neither was the risk
      influenced by the rate of consumption or whether the consumption had occurred at
      a young age. Our study provides clear evidence that aspirin is unrelated to renal
      cell cancer risk, and our findings do not support the hypothesis that analgesics
      containing phenacetin or paracetamol increase the risk, although the number of
      "regular" users and the amount of these types of analgesic consumed were too
      small to confidently rule out a minor carcinogenic effect of phenacetin and
      paracetamol.

PMID- 7829243
TI  - International renal-cell cancer study. III. Role of weight, height, physical
      activity, and use of amphetamines.
AB  - Although numerous studies have identified obesity or high relative weight as a
      risk factor for renal-cell cancer in women, the degree to which this effect is
      present in men remains unclear. A multicenter population-based case-control study
      concerning incident cases of histologically verified renal-cell cancer (n =
      1,732) and age- and sex-matched controls (n = 2,309) was conducted in Australia,
      Denmark, Germany (2 centers), Sweden and the United States. Relative weight was
      estimated by the body mass index, and the association between this factor and
      other factors, such as height, physical activity and use of amphetamines, was
      measured by the relative risk estimated in logistic regression models. Body mass
      index was found to be a risk factor among women and, to a lesser extent, among
      men. A 3-fold increased risk (RR = 3.6, 95% CI = 2.3-5.7) was observed for women
      with a relative weight in the top 5% compared with those in the lowest quartile.
      Rate of weight change (estimated as weight change per annum in kilograms)
      appeared to be an independent risk factor among women but not among men. Physical
      activity and height were unrelated to risk of renal-cell cancer regardless of
      level of BMI, while use of amphetamines was associated with an increased risk
      among men, although no dose or duration effect was seen. Our findings verify the
      link between high relative weight and risk of renal-cell cancer, particularly
      among women. The mechanism that underlies this association is, however, still
      unclear, although the rate of weight change may play a role.

PMID- 7829244
TI  - Incidence of cancer among New South Wales adolescents: which classification
      scheme describes adolescent cancers better?
AB  - This report has the dual purpose of describing patterns of cancer incidence among
      adolescents in New South Wales (NSW), Australia, and comparing adult and
      childhood cancer classification schemes. All cases of cancer incident between
      1972 and 1991 in NSW residents aged 10-19 years were obtained from the population
      based NSW Central Cancer Registry and coded according to Birch and Marsden (1987)
      in addition to routine coding by the Ninth Revision of the International
      Classification of Diseases. The average incidence rate for all cancers combined
      was 158 and 140 per million in males and females respectively. The Birch and
      Marsden category of "carcinomas and other epithelial neoplasms" comprised 22% of
      all cancers in male adolescents and 37% in females. Melanoma alone accounted for
      16% of all cancers in males and 26% in females. Rates of leukaemias and central
      nervous system tumours were similar in the age groups 10-14 years and 15-19
      years. By contrast, lymphomas, bone tumours (males only), soft tissue (males
      only), "germ-cell, trophoblastic and other gonadal tumours" and "carcinomas and
      other epithelial neoplasms" were more common in the older age group. The Birch
      and Marsden classification with its emphasis on morphology provided a clearer
      picture of some types of cancer which occurred frequently among teenagers.
      Cancers common in adults did occur in older adolescents but were less well
      described by the childhood scheme. Cancers of colon and lung were often of
      unusual histological type compared to adult tumours. It would appear appropriate
      to use the childhood classification scheme to describe cancer incidence in
      adolescent age groups, perhaps with minor modification.

PMID- 7829245
TI  - Prostate cancer risk in U.S. blacks and whites with a family history of cancer.
AB  - Prostate cancer occurs more frequently in U.S. blacks than whites. A population
      based case-control study which investigated the association with family history
      of cancer was carried out among 981 men (479 black, 502 white) with
      pathologically confirmed prostate cancer, diagnosed between August 1, 1986, and
      April 30, 1989, and 1,315 controls (594 black, 721 white). Study subjects, aged
      40-79, resided in Atlanta, Detroit, and 10 counties in New Jersey, geographic
      areas covered by population-based cancer registries. Prostate cancer risk was
      significantly elevated among those who reported a history of prostate cancer in
      first-degree relatives (O.R. = 3.2; 95% C.I.: 2.0-5.0), with blacks and whites
      having similarly elevated risks. These risks were unchanged by statistical
      adjustment for job-related socio-economic status, education, income, and marital
      status. Overall, the ORs associated with history of prostate cancer in fathers
      and brothers were 2.5 (95% C.I.: 1.5-4.2) and 5.3 (95% C.I.: 2.3-12.5),
      respectively. Risks associated with a family history of prostate cancer were
      consistently elevated among younger and older subjects. Only small non
      significant excesses of prostate cancer risk were associated with a family
      history of breast, colorectal, or other cancers. While familial occurrence is a
      key risk factor for prostate cancer and likely to be genetically based, the
      similar familial risks among blacks and whites suggest that the ethnic disparity
      in incidence is influenced by environmental factors.

PMID- 7829246
TI  - Plasma levels of the atherogenic amino acid homocysteine in post-menopausal women
      with breast cancer treated with tamoxifen.
AB  - Long-term treatment of breast-cancer patients with the anti-oestrogen tamoxifen
      has been found to be associated with reduced cardiovascular mortality. Plasma
      homocysteine is an independent risk factor for atherosclerotic disease, and its
      level is determined by folate and cobalamin status, and possibly also by
      oestrogen status. We measured the effect of tamoxifen on plasma homocysteine,
      serum cholesterol, serum cobalamin and serum and erythrocyte folate in 31 post
      menopausal women with breast cancer. The plasma homocysteine level was decreased
      by a mean value of 29.8% after 9-12 months and by 24.5% after 13-18 months of
      treatment. Tamoxifen suppressed serum cholesterol by mean values varying between
      7.2% and 17.6% after 3 to 19 months of treatment. There was no correlation
      between changes in plasma homocysteine and serum cholesterol. These findings
      suggest that the homocysteine-lowering effect of tamoxifen may contribute to the
      reduction of cardiovascular mortality observed in patients on adjuvant therapy
      with tamoxifen.

PMID- 7829247
TI  - Genetic characterization of the human papillomavirus (HPV) 18 E2 gene in clinical
      specimens suggests the presence of a subtype with decreased oncogenic potential.
AB  - HPV 18 is associated with 2 divergent phenotypes: (i) aggressive cervical cancer
      and a preponderance of cancer relative to cervical intra-epithelial neoplasia
      (CIN) and (ii) benign warty lesions of the cervix. The E2 gene of HPV 18 encodes
      a regulatory protein that represses viral oncogene transcription and is involved
      in viral replication. Variation within the E2 gene of HPV 18 and its correlation
      with the morphologic grade of associated lesions were analyzed in a sample of 20
      HPV 18-positive cervical specimens representing a spectrum of pathology from low
      grade CIN to cervical cancer. An amplification HPV 18 E2 gene was present in 3 of
      5 cancers, indicating that E2 disruption was not required for cancer development.
      Single-strand conformation polymorphism and PCR analyses revealed a high degree
      of polymorphism throughout the E2 gene. Direct DNA sequencing of both strands of
      a 154-bp fragment revealed a variability of 5.8%. Six intra-epithelial lesions
      contained alterations in common that account for 3.9% of the variation and appear
      to constitute a subtype. Within the 154-bp region, 2 of 3 cervical cancers and 0
      of 12 intra-epithelial lesions were identical to the published HPV 18 sequence.
      DNA sequence analysis of a region extending into the E5 open reading frame
      revealed deletions in the E2/E5 intragenic region that were present in 50% of the
      members of the subtype. Our data demonstrate significant sequence variation
      within the E2 gene and suggest the presence of an HPV 18 subtype with decreased
      oncogenic potential.

PMID- 7829248
TI  - Expression of tissue-type transglutaminase correlates positively with metastatic
      properties of human melanoma cell lines.
AB  - In this study the relationship between tissue-type transglutaminase (TGase2)
      activity and the propensity to metastasize was investigated in human melanoma
      cell lines with different metastatic behavior. TGase2 catalyzes an acyl-transfer
      reaction between peptide-bound glutamine residues and primary amines, including
      the epsilon-amino group of lysine residues. Northern-blot analysis demonstrated
      that TGase2 RNA-expression (3.7 kb) was elevated in highly metastatic cell lines
      (MV3 and BLM) as compared to weakly metastatic ones (IF6 and 530).
      Immunoprecipitation and enzyme assays of TGase2 showed that the differential
      expression at the mRNA level was also reflected at the protein level. These
      findings reveal a positive relation between the expression of TGase2 and the
      metastatic properties of the human melanoma cell lines.

PMID- 7829249
TI  - Photosensitizing efficacy of MTHPC-PDT compared to photofrin-PDT in the RIF1
      mouse tumour and normal skin.
AB  - The new photosensitizer, meso-tetrahydroxyphenylchlorin (mTPHC) was compared with
      Photofrin in the murine RIF1 tumour and in normal mouse skin. A range of mTHPC or
      Photofrin doses were given at intervals of 1 hr to 7 days before illumination.
      mTHPC-PDT resulted in much higher tumour phototoxicity with longer regrowth
      delays and more cures. The RIF1 tumour could be effectively treated with 30 J cm
      1 (interstitial illumination) at 1 day after mTHPC, whereas 4 to 13 times higher
      light doses were required with Photofrin for an equivalent anti-tumour effect.
      High doses of mTHPC also caused more skin phototoxicity (superficial
      illumination) than Photofrin for the 1-day illumination interval. Evaluating both
      tumour and normal skin photosensitization, the largest therapeutic gain factor
      (TGF) for mTHPC-PDT was achieved with a low drug dose (0.15 mg kg-1) at 1 day
      before illumination (TGF = 5.6, relative to Photofrin PDT). The duration of
      cutaneous photosensitivity for mTHPC was shorter than for Photofrin. The light
      dose required to produce a desquamation response in 50% of the animals increased
      more than 20-fold over the period 1 to 7 days after high doses of mTHPC, whereas
      this light dose only increased by a factor of 2 from 1 to 7 days after Photofrin.
      The large therapeutic gains seen for mTHPC-mediated PDT compared to Photofrin,
      plus the rapid fading of skin photosensitization, suggest that mTHPC is a potent
      photosensitizer suitable for clinical testing.

PMID- 7829250
TI  - DNA ploidy and clonal selection in ras + myc-induced mouse prostate cancer.
AB  - An important goal in prostate cancer research is to define specific molecular and
      cellular alterations that are associated with malignant progression. The mouse
      prostate reconstitution model is a relevant and useful system as it allows the
      study of early events in cancer progression under conditions where oncogene
      initiated cells are surrounded by normal tissue. Using this model, activated ras
      and myc oncogenes are introduced into urogenital sinus cells via the recombinant
      retrovirus Zipras/myc 9. After 4 weeks' growth as subcapsular renal grafts,
      poorly differentiated carcinomas are produced in C57BL/6 mice. In this study we
      examined the temporal relationships between morphological alterations, growth,
      DNA ploidy status and clonal selection as determined by Southern blotting in ras
      + myc-initiated carcinomas. Nuclear image analysis demonstrated that the
      emergence of a cycling DNA tetraploid cell population strongly correlated with
      growth and histologic progression. These tightly linked events culminated in the
      outgrowth of mono- or oligoclonal cancer.

PMID- 7829251
TI  - Apoptosis in colorectal tumour cells: induction by the short chain fatty acids
      butyrate, propionate and acetate and by the bile salt deoxycholate.
AB  - The short chain fatty acids acetate, propionate and butyrate are produced when
      dietary fibre is fermented by the colonic bacteria. We have previously shown that
      sodium butyrate induces apoptosis in 3 colorectal tumour cell lines. We have
      extended our study to 3 adenoma and 4 carcinoma cell lines and investigated
      whether propionate and acetate also induce apoptosis. All 3 short chain fatty
      acids induced apoptosis at physiological concentrations, but of the 3, butyrate
      was the most effective. Since these fatty acids are produced as a result of
      bacterial fermentation of dietary fibre, this may in part explain the correlation
      between a high-fibre diet and low colorectal cancer incidence. Sodium butyrate
      induced apoptosis in all 7 of the cell lines studied; however, 2 of the 4
      carcinoma cell lines (PC/JW/FI and S/KS/FI) were more resistant to butyrate
      induced apoptosis than the 3 adenoma cell lines, suggesting that at least some
      carcinomas may evolve mechanisms to protect the cells from the induction of
      apoptosis. The bile acid deoxycholic acid has previously been reported as a
      possible tumour promoter in the large intestine and its levels are reduced by
      dietary fibre. Concentrations of between 10 nM and 0.1 mM had no effect on either
      the proliferation or apoptosis of colonic tumour cells in vitro. However, a
      significant induction of apoptosis was obtained at a concentration of 0.5 mM.
      These results may have significance for the aetiology of colorectal cancer.

PMID- 7829252
TI  - Altered transcription control is responsible for the increased level of
      proliferation-associated P120 in rapidly growing breast carcinoma.
AB  - Transcriptional and post-transcriptional regulation of proliferation-associated
      nucleolar P120 protein expression was examined in 1 normal and 5 malignant breast
      cell lines. The 6 breast cell lines could be placed into 3 categories on the
      basis of in vitro growth rate. BT549 and HBL100 grew rapidly; MCF-7/6, MCF-7/AZ
      and Hs578T grew at a moderate rate; and Hs578N normal epithelia grew slowly.
      There was a significant correlation between the growth rate, measured by
      percentage of S-phase fraction of cells or doubling time of cell numbers and the
      steady-state levels of either P120 protein or P120 mRNA. Next, the mechanisms
      responsible for the increased level of P120 expression, which is associated with
      rapidly growing breast carcinoma, were examined. The stability of P120 mRNA was
      measured by densitometry of quantitative Northern blots of mRNAs from cells
      treated with actinomycin D. Before the expected decay, a sharp increase in P120
      mRNA level was detected shortly after inhibiting the overall RNA or protein
      synthesis. The calculated half-life of P120 mRNA was very similar (1.8 +/- 0.2
      hr) in all 6 cell lines examined. The transcription rate of the P120 gene was
      determined by densitometric analysis of quantitative nuclear run-off assays. A
      significant positive correlation was found between the transcription rate of the
      P120 gene and the steady-state levels of either P120 protein or P120 mRNA. Our
      conclusion is that the expression of P120 protein is transcriptionally regulated
      in these breast cells. Therefore, the characteristically high level of P120
      protein and mRNA found in most breast carcinomas is due to the altered
      transcription rate of the P120 gene in transformed cells.

PMID- 7829253
TI  - The effect of platelets on invasiveness and protease production of human mammary
      tumor cells.
AB  - Interaction of tumor cells with platelets facilitates metastasis of tumor cells.
      It has been proposed that platelets protect tumor cells against the host's immune
      defense and enhance tumor-cell extravasation. In the present work we show that
      platelets increase the invasiveness of 3 mammalian cell lines (MCF-7, ZR-51 and
      MDA-MB231) through extracellular matrix, and propose this as an additional
      mechanism by which platelets facilitate metastasis. Since gelatinase and
      urokinase have both been implicated in degradation of the extracellular matrix
      and cell migration, and therefore in tumor invasion, we have also analyzed
      whether the interaction of platelets with tumor cells can modify the secretion of
      these proteases by tumor cells. MDA-MB231, which was the most invasive cell line
      among the 3 tested and was the most potent in inducing platelet aggregation,
      secreted the highest level of urokinase and was the only one in which gelatinase
      was detected. While platelets had no significant effect on the urokinase activity
      expressed by these cells, they induced in MDA-MB231 an important increase in the
      secretion of gelatinase, which can be reproduced by both platelet membrane and
      platelet releasate of activated platelets. This increase in gelatinase could be
      responsible, at least in part, for the increased invasiveness of these cells,
      since added TIMP-1 significantly reduced the number of cells which traversed
      matrigel.

PMID- 7829254
TI  - HTLV-I infection among Nivkhi people in Sakhalin.

PMID- 7829255
TI  - Cervical cancer and herpes simplex virus type 2: case-control studies in Spain
      and Colombia, with special reference to immunoglobulin-G sub-classes.
AB  - Two case-control studies, including 449 histologically confirmed cases of
      cervical intra-epithelial neoplasia (CIN) III and 425 controls, and 2 studies on
      invasive cervical cancer, involving 316 histologically confirmed cases and 330
      population controls, were conducted in Colombia and Spain to assess the role of
      herpes simplex virus type 2 (HSV-2) in cervical neoplasia. Antibodies to this
      virus were also measured in the sera of 931 husbands of cases and controls. A
      serological assay using type-specific antigens, glycoprotein C for type I (gC-I)
      and glycoprotein G for type 2 (gG-2) was employed. Immunoglobulin-G (IgG) sub
      classes, IgG1 and IgG3, were measured in women positive for HSV-2 antibodies. No
      increase in risk of CIN III or invasive cancer was found in women whose sera or
      whose husbands' sera were positive to HSV-2. However, compared with women
      negative to HSV-2, the risk of CIN III progressively increased with increasing
      levels of IgG1. The trend was statistically significant in Colombia. There was
      also a statistically significant increasing trend in risk of invasive cancer with
      levels of IgG1 in Spain. The levels of IgG3 and its ratio to IgG1, which may
      indicate recurrent infections, were not associated with the risk of either type
      of cancer. When the association with IgG1 was analyzed by human papillomavirus
      (HPV) DNA status, as determined by polymerase chain reaction, the trend was
      clearer in women whose HPV status was not determined or in those with negative
      HPV DNA. These results suggest that the role of HSV-2 is merely marginal and do
      not support the hypothesis that recurrent HSV-2 infections are of importance for
      cervical neoplasia.

PMID- 7829256
TI  - High expression of UDP-N-acetylglucosamine: beta-D mannoside beta-1,4-N
      acetylglucosaminyltransferase III (GnT-III) in chronic myelogenous leukemia in
      blast crisis.
AB  - The activity and mRNA expression of UDP-N-acetylglucosamine: beta-D mannoside
      beta-1,4-N-acetylglucosaminyl transferase III (GnT-III: EC 2.4.1.144) were
      investigated in hematological malignancies. GnT-III activity was elevated in
      patients with chronic myelogenous leukemia (CML) in blast crisis and patients
      with multiple myeloma (MM), as compared to normal healthy subjects and patients
      with other hematological malignancies including CML in chronic phase. The GnT-III
      transcript was the same size in leukemic cells from various hematological
      diseases and cell lines, while expression of the transcript was not found to
      correlate significantly with enzyme activity, implying that post-translational
      modification might regulate the activity of GnT-III. Southern-blot analysis
      showed no significant variation in the structure and position of the GnT-III
      genome, indicating that the gene is present as a single copy without isoforms.
      Furthermore, analyses by immunoprecipitation and Western blot revealed that high
      GnT-III activity in KU812 cell, a CML cell line, resulted in an increase in E4
      PHA binding to CD45, a major surface glycoprotein of the leukocyte, indicating
      that more bisecting GlcNAc was added to CD45 catalyzed by elevated GnT-III.

PMID- 7829257
TI  - Inhibition of bispecific monoclonal antibody (bsAb)-targeted cytolysis by human
      anti-mouse antibodies in ovarian carcinoma patients treated with bsAb-targeted
      activated T-lymphocytes.
AB  - T lymphocytes of 8 patients with ovarian cancer were targeted to the tumor cells
      using F(ab')2 fragments of a bispecific monoclonal antibody (bsAb), specific for
      CD3 (a component of the T lymphocyte receptor for antigen) and for the folate
      receptor MOv18 (overexpressed by ovarian carcinoma cells) as part of a phase I/II
      study. Phase I (days 0 to 3) consisted of increasing intraperitoneal (i.p.)
      numbers (10(6)-10(9)) of bsAb-targeted T lymphocytes plus low-dose interleukin-2
      (IL-2). Phase II (days 6 to 13, and 27 to 33) consisted of daily i.p. infusions
      of 10(9) targeted T lymphocytes, 2 mg soluble bsAb, and low-dose IL-2. Using
      enzyme-linked immunosorbent assays (ELISA), human anti-mouse antibodies (HAMA)
      were detected in all patients: in the serum from day 13 onwards and in the
      peritoneal fluid from day 20 onwards. A significant proportion of the HAMA
      appeared to be directed against the idiotypes of the bsAb specific for CD3 and
      MOv18, as suggested by (1) the clearly higher ELISA titers against OC/TR bsAb as
      compared to those against a monoclonal antibody (MAb) with unrelated specificity,
      and (2) failure to abrogate the capacity of peritoneal fluid containing HAMA to
      block the binding of OC/TR bsAb to MOv18+ or CD3+ cells by absorption of human
      anti-mouse IgG-framework antibodies in peritoneal fluid to immobilized mouse IgG.
      The OC/TR-targeted cytolysis of the MOv18+ ovarian carcinoma cell line Igrov-I by
      autologous T lymphocytes was inhibited by peritoneal fluid samples containing
      relatively high HAMA titers. Such inhibitory activity was never detected at the
      start of phase II, but coincided with the last series of i.p. infusions of
      targeted T lymphocytes in 2 patients.

PMID- 7829258
TI  - A low incidence of p53 mutations in pre-malignant lesions of the oral cavity from
      non-tobacco users.
AB  - To determine the incidence of p53 mutations in pre-malignant lesions of the oral
      cavity from individuals without prior history of tobacco use, we have analyzed
      the conserved regions of the p53 gene (exons 5-9) in archival oral cavity lesion
      specimens obtained from patients with varied tobacco use histories, by polymerase
      chain reaction/single strand conformational polymorphism (PCR/SSCP) and DNA
      sequencing analysis. Twenty-six lesions were analyzed from 14 patients, with
      multiple lesions obtained from 8 patients. Six of these patients used tobacco, (3
      being cigarette smokers, 1 ex-cigarette smoker, 1 moderate cigar smoker and 1
      snuff chewer). The remaining 8 patients had no prior history of tobacco use.
      Thirteen of the pre-malignant lesions exhibited severe dysplasia, 9 exhibited
      moderate dysplasia and 4 exhibited mild dysplasia. Four of the 26 lesions
      exhibited p53 mutations, each being from a tobacco user. None of the 13 lesions
      from never-tobacco users exhibited p53 mutations. There was a significantly
      higher p53 mutation incidence in pre-malignant lesions from tobacco users
      (including ex-smokers) than in non-tobacco users as well as in cigarette smokers
      plus snuff chewers than in non-tobacco users. Two of the mutations were observed
      in lesions exhibiting severe dysplasia: 1 in a lesion exhibiting moderate
      dysplasia and 1 in a lesion exhibiting mild dysplasia. These data suggest that
      p53 mutation may be a very early event in oral cavity tumor progression and
      demonstrate that pre-malignant lesions obtained from non-tobacco users do not
      exhibit p53 mutations.

PMID- 7829259
TI  - Risk of subsequent malignant neoplasms among 470,000 cancer patients in Finland,
      1953-1991.
AB  - Because of increasing numbers of incident cancers and improving survival rates,
      more and more cancer patients are at risk of subsequent primary malignant
      neoplasms. The potential carcinogenicity of cancer therapies raises further
      concern regarding this unwanted long-term side effect. The objective of this
      cancer-registry-based study was to assess the trends in the risk of subsequent
      primary malignancies among cancer patients on a nationwide public-health level.
      The 470,000 cancer patients registered between 1953 and 1991 in Finland were
      followed up for subsequent primary neoplasms, and 19,800 subsequent malignant
      neoplasms were observed, yielding an overall standardized incidence ratio (SIR)
      of 1.00 for men and 1.25 for women. Substantial variation was observed in the SIR
      by the site of subsequent malignancy. The adjusted relative risk derived from
      multiple regression analyses showed only a slight increase by follow-up interval.
      Overall, the excess relative risk of subsequent malignancies was low, since the
      majority of cancer patients are old and at low relative risk. Patients under the
      age of 50 years, however, were at 70% increased risk, and the overall relative
      risk increased by 50% from the 1950s to the 1980s. Subsequent neoplasms among
      cancer patients do not pose a major public-health problem, but the possibility of
      subsequent cancers must be borne in mind in decisions concerning therapy and in
      clinical follow-up.

PMID- 7829260
TI  - Analysis of the NF2 tumor-suppressor gene and of chromosome 22 deletions in
      gliomas.
AB  - Recurrent deletions of chromosome fragments observed in neoplasms are thought to
      participate in tumor development through the inactivation of tumor-suppressor
      genes. In gliomas, the most frequent deletions involve chromosome arms 9p, 10q,
      17p, 19q and 22q. We have analysed deletions of chromosome 22 in gliomas by
      studying loss of heterozygosity (LOH) at 8 microsatellite loci. LOH for this
      chromosome fragment was observed in 17/70 (24%) cases, most of them encompassing
      the region which encodes the gene altered in neurofibromatosis 2 (NF2), an
      inherited disease which predisposes to tumors of the nervous system. To
      investigate the possible involvement of the NF2 tumor-suppressor gene in the
      tumorigenesis of gliomas, we searched for alterations in its genomic structure
      and in its mature transcript. Northern-blot and reverse transcriptase-PCR
      experiments showed that the NF2 transcript is expressed and does not demonstrate
      obvious structural alterations. Moreover, analysis, at the genomic level, of the
      16 coding exons of the NF2 gene by denaturing gradient gel electrophoresis failed
      to detect any somatically acquired point mutations. Altogether, these data
      strongly suggest that, although gliomas demonstrate recurrent chromosome 22
      deletions most frequently encompassing the NF2 region, the NF2 gene is not
      altered in these tumors.

PMID- 7829261
TI  - A dose-response curve for sun exposure and basal cell carcinoma.
AB  - A population-based case-control study of sun exposure and basal cell carcinoma
      (BCC) was conducted in Western Australia in 1988. Its aim was to examine the
      relationship between risk of BCC and the amount and pattern of sun exposure. This
      report deals with amount of exposure. The odds ratios (ORs) for BCC on the head
      and neck and limbs decreased with increasing total exposure, whereas the opposite
      was observed for BCC on the less heavily exposed trunk, with the highest OR in
      those with the greatest exposure. In an analysis of all body sites together in
      which the total hours of exposure to the specific site was treated as a
      continuous variable, an initial rise in risk of BCC was seen with a peak OR of
      1.4 at about 35,000 hr of exposure, followed by a fall. In contrast to these site
      specific patterns, lifetime accumulated sun exposure of the whole body showed no
      appreciable association with BCC either in total or for working days only. Risk
      of BCC was positively associated with lifetime exposure on non-working days,
      however, with an OR for higher than baseline categories of around 1.7. There was
      a significant interaction between ability to tan and total and occupational sun
      exposure. Risk increased with increasing exposure in those who tanned well but
      not in those who tanned poorly. This pattern is consistent with other
      observations which indicate that beyond a certain level of sun exposure risk of
      BCC does not increase further.

PMID- 7829262
TI  - Does intermittent sun exposure cause basal cell carcinoma? a case-control study
      in Western Australia.
AB  - Our report deals with the relationship of pattern and timing of sun exposure to
      basal cell carcinoma (BCC) in a population-based case-control study conducted in
      Western Australia in 1988. The main measure of intermittent exposure was based on
      the amount of exposure on non-working days relative to that over the whole week.
      Outdoor recreational activities, holidays and sunburn were also considered to be
      markers of intermittent exposure. We observed a statistically significant
      increase in risk of BCC with increasing proportion of weekly sun exposure
      obtained at the weekend, especially in late teenage (OR = 3.9, 95% CI 1.9-7.8 for
      maximum intermittency of exposure), exposure of the site of skin cancer during
      holidays (OR = 1.9, 95% CI 1.1-3.1 for the highest exposure quarter) and sunburn
      to the site (ORs of 1.8 for 3-10 and 1.5 for 11+ sunburns in a lifetime). Risk of
      BCC increased substantially with increasing intermittency in poor tanners but not
      at all in good tanners. Our data suggest that a particular amount of sun exposure
      delivered in infrequent, probably intense increments will increase risk of BCC
      more than a similar dose delivered more continuously over the same total period
      of time.

PMID- 7829263
TI  - Proteolytic enzymes at various stages of oncogenic transformation of rat
      fibroblasts. I. Aspartyl and cysteine proteinases.
AB  - Aspartyl and cysteine proteinases at distinct stages of carcinogenesis were
      analyzed in rat embryo fibroblasts, sequentially immortalized and transformed by
      2 different genes: the early region of simian adenovirus SA7 and c-Ha-ras
      oncogene. The dynamics of expression and distribution of proteinases throughout
      the transformation process were examined. It was shown that in immortalized and
      transformed cells the activities of the aspartyl and cysteine proteinases were
      expressed to a variable degree and that the expression was dependent on cell
      propagation time in vitro. The increase in activity both of cathepsin-D-like
      aspartyl proteinase and of cathepsin-L- and -B-like cysteine proteinases in cell
      lysates was correlated with the stages of fibroblast transformation
      (immortalization and tumorigenic transformation). In all cell types the major
      part of cysteine proteinases was localized inside the cell, while the cathepsin-D
      like proteinase was apparently predominant among secreted proteinases. The
      cathepsin-L-like proteinase accounts for the major part of the cysteine
      proteinase activity as measured by Z-Phe-Arg-MCA hydrolysis. We suggest that
      considerable portions of the cathepsin-D- and -L-like proteinases in all cell
      lines studied are secreted as a complex with inhibitor(s) and that inhibitor
      expression plays an important role in regulating the activity of cathepsin-D-like
      proteinase at different stages of transformation. Cathepsin-L-like proteinase is
      probably secreted in the precursor form.

PMID- 7829264
TI  - Co-expression of urokinase, urokinase receptor and PAI-1 is necessary for optimum
      invasiveness of cultured lung cancer cells.
AB  - We investigated the importance of the urokinase (uPA)-plasmin system in fostering
      invasion of human lung cancer cells through artificial basement membranes
      composed of Matrigel. Eight cell lines (including 1 small cell and 7 non-small
      cell lines) were examined. One cell line did not express any components of the
      urokinase system. Four cell lines had substantial levels of endogenous uPA
      detectable on their surfaces. Three of these cell lines co-expressed the
      plasminogen activator inhibitor PAI-1 in addition to uPA. Assays for invasiveness
      revealed 4 cell lines capable of traversing a Matrigel barrier, including the 3
      which co-expressed uPA, PAI-1 and uPA receptor. Surprisingly, the cell line
      expressing only uPA and uPA receptor displayed no invasive capacity despite
      levels of secreted uPA more than 20-fold higher than the other cell lines
      studied. Based on these observations, we hypothesized that both uPA and PAI-1
      might be important for invasion by lung tumor cells, at least in vitro. We
      therefore tested polyclonal antibodies which inhibit uPA and PAI-1 activity for
      their effects on the highly invasive H292 cell line. After 3 days, invasive
      capacity was inhibited by antibodies to both uPA and PAI-1 in a dose-dependent
      manner. The plasmin inhibitor aprotinin reduced H292 cell invasion by 70%. Taken
      together, our data demonstrate that in cultured human lung cancer cells the uPA
      plasmin system is important in promoting invasion into basement membranes and
      suggest that a critical balance between uPA and PAI-1 is necessary for optimal
      invasiveness. Our data are consistent with results from recent clinical studies
      showing that PAI-1 expression in tumor tissue is an adverse prognostic feature.

PMID- 7829265
TI  - Phenylacetate synergizes with retinoic acid in inducing the differentiation of
      human neuroblastoma cells.
AB  - Phenylacetate, a natural metabolite of phenylalanine which was originally
      described as a plant growth hormone, has recently gained attention as a possible
      differentiation inducer for a variety of human tumor cell types. This interest
      prompted us to assess the ability of sodium phenylacetate (NaPA) to promote the
      differentiation of human neuroblastoma cells, both alone and in combination with
      retinoic acid (RA), a known inducer of neuroblastoma differentiation and
      maturation. Using the LA-N-5 cell line, we have determined that NaPA can
      stimulate the differentiation of neuroblastoma cells, as evidenced by dose
      dependent inhibition of cell proliferation, neurite outgrowth, increased
      acetylcholinesterase activity and reduction of N-myc expression. Furthermore,
      NaPA and RA synergized in inducing differentiation, in that combination treatment
      resulted in cessation of cell growth along with morphologic and biochemical
      changes indicative of the loss of malignant properties. We have determined that
      NaPA can markedly enhance mRNA levels of the nuclear RA receptor-beta (RAR beta)
      in LA-N-5 cells prior to morphologic or other phenotypic changes induced by this
      compound. This effect appeared to be distinct from the ability of NaPA to alter
      tumor cell lipid metabolism via inhibition of protein isoprenylation. Thus among
      its varied effects on LA-N-5 cells, NaPA appears to interact with the RA pathway
      at the nuclear level by up-regulating RAR beta expression.

PMID- 7829266
TI  - Inhibition of aberrant crypt growth by non-steroidal anti-inflammatory agents and
      differentiation agents in the rat colon.
AB  - Aberrant crypts are aggregates of single to multiple colonic crypts evidencing
      hallmarks of dysplasia and may be the earliest detectable pathological lesions
      for colon cancer. The aberrant crypt assay has been developed in 2 protocols. In
      one, putative chemoprevention agents are tested for inhibitory effects when
      administered concomitantly with a carcinogen. In the other, the objective of this
      study, aberrant crypts were induced in F344 rats by parenteral injection of the
      colon carcinogen azoxymethane (AOM) and allowed to develop for 4 weeks, when an
      average of 90-100 aberrant crypt foci per colon were found in the methylene blue
      stained colon. Then, during the second 4 weeks of the experiment, aberrant crypts
      were allowed to further develop to a frequency of > 150 foci per colon, a time
      when multi-crypt foci were observed. During this time we tested the inhibitory
      effects of 4 analgesic drugs and 2 differentiation agents for effects of aberrant
      crypt growth and development. We found the non-steroidal anti-inflammatory drugs
      piroxicam, aspirin and ibuprofen, but not acetaminophen, to be effective in
      suppressing aberrant crypt formation or the progression to foci of multiple
      aberrant crypts. Treatment with chemosuppressing agents 13-cis-retinoic acid (13
      cRA) and 4-hydroxyphenretinamide (4-HPR), known differentiating agents, however,
      did suppress expansion of aberrant crypt foci, with 13-cRA being the much more
      potent agent.

PMID- 7829267
TI  - Catechol interferes with TGF-beta-induced elimination of transformed cells by
      normal cells: implications for the survival of transformed cells during
      carcinogenesis.
AB  - We have recently shown that TGF-beta-treated normal fibroblasts are able to
      induce apoptosis of transformed fibroblasts, leading to their elimination. Here
      we describe a test system that allows the quantitative analysis of the
      elimination of G418-resistant transformed cells by TGF-beta-treated normal cells.
      This assay system was used to screen for substances that interfere with the
      elimination of transformed cells. Catechol and hydroquinone, but not resorcinol,
      were found to represent potent antagonists of TGF-beta-induced elimination of
      transformed cells by normal cells. Protection of transformed cells from negative
      effects derived from their cellular environment defines a hitherto unrecognized
      crucial mechanism for the survival of transformed cells. The protective effect of
      catechol as seen in this experimental system may act in concert with its co
      carcinogenic and promoting activities during carcinogenesis.

PMID- 7829268
TI  - Suppression of Burkitt's lymphoma tumorigenicity in nude mice by co-inoculation
      of EBV-immortalized lymphoblastoid cells.
AB  - EBV-immortalized B-lymphoblastoid cell lines (LCL) inoculated s.c. into T-cell
      deficient nude mice regress completely after a short initial growth period. We
      tested whether the putative host response underlying this phenomenon might also
      be directed against progressively growing Burkitt's lymphoma (BL) tumors in nude
      mice. Outgrowth of BL tumors was suppressed when cells of the highly tumorigenic
      BL cell line BL 60 were mixed with cells of the autologous LCL IARC 277 before
      s.c. inoculation into nude mice. Even when the cells were inoculated separately
      and simultaneously into contralateral flanks of the mice, regression of initially
      growing BL tumors could be observed, albeit with reduced frequency and dependent
      on the dose of LCL cells. Tumor growth of BL 60 cells could also be suppressed by
      co-inoculation with the non-autologous LCL IARC 174 and IARC 277 cells could
      suppress growth of the non-autologous BL cell line Eli. Pronounced infiltration
      with murine (m)CD-11b-positive mouse macrophages and mCD-8a-positive mouse
      lymphoid cells, most probably natural killer cells, was seen in histological
      tissue sections of regressing BL 60 tumors when LCL cells were inoculated
      contralaterally. In regressing BL tumors, these mouse cells were present not only
      in necrotic areas but also in vital BL tissue, indicating that infiltration of
      mouse cells had taken place before the development of necrosis. Since tumor
      infiltrating mouse cells can be activated at least by some human cytokines, we
      measured cytokine production of BL 60 and IARC 277. High amounts of IL 6 and IL
      10 were produced by the LCL cells, whereas IL-6 and IL-10 production by the BL 60
      cells was beyond or close to the detection threshold. In addition, IL 8 was
      secreted up to 5-fold more by the LCL than by the BL cells. The results presented
      here thus suggest a host response of the nude mouse, which is triggered by
      cytokines released from the LCL but, once induced, is directed also against BL
      cells.

PMID- 7829269
TI  - Effect of VK framework-1 glycosylation on the binding affinity of lymphoma
      specific murine and chimeric LL2 antibodies and its potential use as a novel
      conjugation site.
AB  - A potential asparagine (Asn)-linked glycosylation site was identified in the VK
      FRI sequence of an anti-B lymphoma monoclonal antibody (MAb), LL2.SDS-PAGE
      analysis and endo-F treatment of both murine and chimeric LL2 antibodies
      indicated that this site was glycosylated; however, no differences in the binding
      affinity to Raji cells were observed between the native murine LL2 and the endo-F
      deglycosylated murine LL2 antibodies. Elimination of the glycosylation site from
      the chimeric LL2 antibody was accomplished by an Asn to Gln mutation in the tri
      acceptor site found in the light chain. The resultant aglycosylated chimeric LL2
      exhibited a similar Raji cell binding affinity to that of the glycosylated form.
      The results are in agreement with computer modeling studies which suggested the
      lack of interactions between the oligosaccharide moiety and the CDRs. The finding
      is interesting because it enables a wider choice of human framework sequences,
      which in most cases do not have a corresponding glycosylation site, for the
      humanization of the LL2 VK domain, as well as a greater latitude of host
      expression systems. Most importantly, the LL2 VK carbohydrate moiety might be
      used as a novel conjugation site for drugs and radionuclides without compromising
      the immunoreactivity of the antibody.

PMID- 7829270
TI  - Tumor-promoting activity of 2,4-dinitrofluorobenzene.
AB  - The aim of this study was to determine whether the skin-sensitizing agent 2,4
      dinitrofluorobenzene (DNFB) would elicit the same morphological and biochemical
      events that are characteristic of 12-O-tetradecanoylphorbol-13-acetate (TPA).
      While single applications of 0.1% or 0.2% DNFB produced only mild epidermal
      hyperplasia, multiple applications produced pronounced hyperplasia. Compared with
      TPA, a single application of DNFB produced small increases in ODC activity,
      although a second DNFB treatment produced a greater response. Both DNFB and TPA
      caused marked induction of ODC, c-fos and c-jun mRNA. Vascular permeability
      increased significantly in response to DNFB, such that after 15 hr the response
      was quantitatively the same as for TPA. Repeated TPA produced the same response
      as a single application, but repeated DNFB resulted in a response that was half
      that of TPA. In contrast to TPA, DNFB failed to activate partially purified
      protein kinase C (PKC), although it did cause transient down-regulation of
      activity 15 hr after treatment. The ability of DNFB to induce ODC activity,
      however, was unaffected by prior down-regulation of PKC. DNFB was also shown to
      promote tumors in initiated SSIN mice. Twice-weekly applications of 0.1% or 0.2%
      DNFB resulted in approximately 65% and 85% of the mice developing an average of
      2.0 or 3.2 tumors each, respectively. These results demonstrate that DNFB elicits
      many of the same changes as TPA and that it does so in a PKC-independent manner.

PMID- 7829271
TI  - Expression of a B-cell marker, CD24, on nasopharyngeal carcinoma cells.
AB  - Random sequencing of clones from a lambda gt10 cDNA library, made from mRNA
      expressed in an Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma
      (NPC) has revealed the gene transcript of human CD24. The CD24 antigen, a
      glycosylphosphatidylinositol-anchored cell surface molecule, has been identified
      as a B-cell marker that is lost during cell maturation. We show here that it is
      expressed on 3 NPC xenografts, previously defined as consisting of poorly
      differentiated epithelial cells, and on an NPC biopsy. In the case of the former,
      the level of expression of CD24 corresponds to the EBV load. A B-lymphoblastoid
      cell line carrying the same EBV genome as one of the tumours, C15, and an EBV
      negative Burkitt's lymphoma cell line do not display the antigen, but epithelial
      like cells of a laryngeal tumour cell line (Hep2) do express it. Our data suggest
      that CD24 may be a marker of cell differentiation not only for B cells but also
      for epithelial cells and may have an indirect association with EBV gene
      expression.

PMID- 7829272
TI  - Vaccination of rabbits with recombinant vaccinia virus carrying the envelope gene
      of human T-cell lymphotropic virus type I.
AB  - Two groups of 3 rabbits each were immunized with either recombinant vaccinia
      virus, WR-SFB5env, carrying the human T-cell lymphotropic virus type I (HTLV-I)
      env gene at the site of the hemagglutinin gene of the WR strain, or control
      vaccinia virus, HA-WR, lacking the functional hemagglutinin gene. All 6 rabbits
      responded with anti-vaccinia virus antibodies. WR-SFB5env elicited anti-HTLV-I
      env antibodies but no vesicular stomatitis virus (HTLV-I) pseudotype neutralizing
      antibodies in all 3 rabbits. After 10 weeks, the animals were challenged by
      transfusion of blood from an HTLV-I-infected rabbit. Two of the 3 vaccinated
      rabbits and all 3 control rabbits became infected with HTLV-I, as indicated by
      seroconversion and detection of HTLV-I proviral sequences by polymerase chain
      reaction. The rabbit that had been protected from initial challenge became
      infected with HTLV-I upon rechallenge 12 weeks after the first challenge. In view
      of the proven prophylactic effect of passive immunization against HTLV-I, our
      vaccine trial failed because WR-SFB5env was incapable of inducing neutralizing
      antibodies against HTLV-I in the immunized animals. It remains to be studied
      whether cell-mediated immunity such as antibody-dependent cellular cytotoxicity
      was involved in the temporary protection of I vaccinated rabbit.

PMID- 7829273
TI  - Antiproliferative activity of taxol on human tumor and normal breast cells vs.
      effects on cardiac cells.
AB  - The antiproliferative activity of the chemotherapeutic agent taxol was evaluated
      on 2 normal and 2 carcinoma human breast-cell lines and compared with its effects
      on newborn rat cardiac cells growing in vitro. Relatively little difference in
      ID50 response (ranging from 0.6 to 2.0 ng/ml) to taxol was found between normal
      and tumorous breast epithelial cells. Arrhythmias and slowing of beat frequencies
      of cardiac cells were induced by taxol but at doses approximately 10 times higher
      than those necessary to inhibit proliferation in dividing cells. Microtubules
      assayed by immunostaining appeared to be similarly retracted around the nucleus
      in both breast and heart cells. Overall, our results suggest that taxol does not
      selectively inhibit the growth of tumor vs. normal human breast cells. They also
      support the hypothesis that effects on microtubule integrity are associated with
      effects on cardiac function and that the clinical cardiac activity of taxol
      already reported may be due, at least in part, to a direct effect of taxol on
      cardiac cells as demonstrated in these in vitro studies. Thus, caution is needed,
      in view of possible cardiac effects, when using taxol in future clinical
      protocols, especially when combined with other cardioactive agents such as
      Adriamycin.

PMID- 7829274
TI  - Production of soluble HLA-class-I molecules by IFN-gamma-induced colon
      adenocarcinoma cells.
AB  - High levels of soluble HLA-class-I molecules (sHLA) were found to be produced in
      a time- and dose-dependent manner by colon-adenocarcinoma Colo205 cells in
      response to IFN-gamma stimulation. Among other cytokines tested, only IL-6, TNF,
      IFN-alpha and IFN-beta showed weak inducibility. IFN-gamma-induced production of
      sHLA was synergistically enhanced by IL-1 alpha, IL-6 or TNF, and combined
      treatment with TNF and IL-6 exhibited an additive to synergistic induction.
      Expression of sHLA is unlikely to result from IFN-gamma-induced enhancement of
      overall HLA-class-I expression, as at low concentrations IFN-alpha, IFN-beta and
      IFN-gamma stimulated increased expression of cell membrane HLA-class-I molecules
      in Colo205 cells with almost equal efficiency, whereas only IFN-gamma induced
      high level production of sHLA. Immunoblotting with a monoclonal antibody
      recognizing beta 2-microglobulin-free HLA-class-I heavy chain revealed 3 major
      forms of sHLA heavy chain, i.e., 45/43-, 37- and 33-kDa molecules, in the culture
      supernatants of IFN-gamma-induced Colo205 cells. The 45/43-kDa proteins can be
      partitioned into Triton X-114, representing intact HLA-class-I heavy chains shed
      from the cell membrane. The hydrophilic 37- and 33-kDa heavy chain, which
      remained almost exclusively in the aqueous phase after extraction with Triton X
      114, could well be due to alternative RNA splicing, with deletion of exon 5
      encoding the hydrophobic transmembrane region of membrane-anchored HLA-class-I
      heavy chain.

PMID- 7829275
TI  - A comparison of abstinence-oriented and indefinite methadone maintenance
      treatment.
AB  - Advantage was taken of a natural experiment to compare the outcome of abstinence
      oriented and indefinite methadone maintenance. Subjects assigned to an abstinence
      oriented program were significantly more likely than those assigned to indefinite
      maintenance to use heroin (OR 1.3) and amphetamines (OR 2.8) during the first 2
      years of methadone treatment but less likely to use benzodiazepines (OR 0.7).
      Subjects discharged from the abstinence-oriented program were significantly more
      likely to relapse and return to maintenance treatment (RR, first 6 months, 4.2).
      The abstinence-oriented program was also less able to attract heroin addicts into
      maintenance treatment.

PMID- 7829276
TI  - Controlled drinking and abstinence in alcoholic men: beliefs influence actions.
AB  - A group of alcoholic men were asked 8 years postdischarge from hospital if they
      could drink alcohol with control. Subjects who said "no" (the NCD group) were
      compared to those who said "yes" (the CD group). A majority of the NCD group had
      been abstinent during the year preceding the 8-year evaluation, whereas none of
      the CD group had been. In the model developed, troubles resulting from drinking
      are seen as instrumental in changes from a CD to a NCD belief. The clinical
      relevance of our results is discussed.

PMID- 7829277
TI  - Estimating the number of heroin users: a review of methods and empirical findings
      from The Netherlands.
AB  - This article reviews major methods applied to estimate the number of heroin users
      in a community, predominantly urban areas. The main focus is on applicability of
      methods to the available data. Methodologies are evaluated with regard to
      reliability, validity, and feasibility from the perspective of empirical
      findings, in particular in the Netherlands. Findings from Amsterdam and Rotterdam
      are presented in more detail in order to discuss major criteria for application
      of the capture/recapture and the nomination techniques.

PMID- 7829278
TI  - The relationships among family problems, friends' troubled behavior, and high
      risk youths' alcohol/other drug use and delinquent behavior: a longitudinal
      study.
AB  - Data from an ongoing longitudinal study of juvenile detainees are used to test a
      structural model of the relationships among their alcohol/other drug use and
      other delinquent behavior, their family problems, and friends' troubled behavior.
      The hypothesized model fitted the data well. Implications of the results are
      drawn in regard to theory and program policy.

PMID- 7829279
TI  - Substance use among Hungarian students.
AB  - There is very little empirical data on drug and alcohol use among Hungarian
      adolescents. The purpose of this pilot project was to develop instrumentation and
      methods that could be used to assess legal and illegal substance use among
      Hungarian adolescents. A Hungarian translation of The American Drug and Alcohol
      Survey was developed and adapted to the unique circumstances of Hungarian
      patterns of use. This survey was tested with 234 students, 135 females and 99
      males, from Grades 8 and 11 enrolled in public schools, in Gyor, Hungary during
      1991-1992. The students reported little or no substance use other than use of
      alcohol and tobacco. Older students were more likely than younger students to be
      involved with alcohol and cigarettes. Females and males were equally likely to
      try alcohol, but males were more likely to have been drunk than females. Despite
      the low reported use of substances other than alcohol and tobacco, students
      demonstrated attitudes toward drug use that may place them "at risk" for future
      use.

PMID- 7829280
TI  - Long-term effects of adolescent drug use in the Israeli middle class.
AB  - This is a self-report study of a purposive sample of 111 middle-class Israelis in
      their 30s. The sample, designed to overrepresent adolescent drug experience,
      included 53 subjects (47.7%) reporting having tried illicit drugs during
      adolescence (epidemiological data indicate approximately 7% percent adolescent
      drug use in Israel). None of the users was apprehended. Comparing the users with
      the nonusers on variables indicating adult conformity, adjustment, and subjective
      well-being revealed no significant difference between the two groups.

PMID- 7829281
TI  - Suicide attempt histories in alcohol-dependent men: differences in psychological
      profiles.
AB  - Fifty-three alcohol-dependent men without additional Axis I disorders were
      divided into two groups based on past history of suicide attempts (SP = suicide
      positive, N = 15; SN = suicide negative, N = 38). Post-hoc analysis revealed that
      the two groups were matched for age, racial makeup, family history of suicide,
      and total number of years of drinking. A significantly higher percentage of SP
      group patients had personal and family histories of either illicit drug use, past
      psychiatric treatment, or both. Psychological profiles demonstrated exaggerated
      tendencies toward sociopathy, attitudinal deviance, heightened activity, anxiety,
      depression, hostility, and disordered thinking among the SP patients. These
      findings highlight the importance of designing individualized relapse prevention
      programs.

PMID- 7829282
TI  - Increasing alcoholic patients' aftercare attendance.
AB  - Of a sample of 100 patients on an inpatient alcohol rehab unit, 50 were assigned
      to a weekly group therapy session in the aftercare clinic. Those inpatients with
      aftercare clinic exposure prior to discharge were more likely to return for
      aftercare. In a second study of 100 inpatients the effect of having a counselor
      who would continue to follow them in aftercare was explored. Half the sample had
      a counselor whose primary assignment was in the aftercare clinic and thus could
      work with them on a continuing basis. The other half had a counselor whose
      primary assignment was on the inpatient unit and would not be able to continue
      with them. Counselor continuity had no impact on aftercare follow through.

PMID- 7829283
TI  - The modality effect: a result of methodology?
AB  - Modality differences for short-term (STM) and long-term memory (LTM) were
      investigated. Sixty-eight subjects participated in one of four conditions:
      Auditory STM, Verbal STM, Auditory LTM, and Verbal LTM. Analysis of the number of
      words correctly recalled showed a significant interaction between modality and
      store. Contrary to both Engle and Mobley's (1976) and Penney's (1975, 1989a,
      1989b) findings, further analysis showed that the auditory mode was superior in
      STM and that no modality difference existed in LTM. It was concluded that the LTM
      modality effect is less robust than that found in STM. Possible methodological
      reasons for the conflicting results of the past as well as areas of potential
      future research were discussed.

PMID- 7829284
TI  - The effects of picoTesla range magnetic fields on visuospatial functions in
      multiple sclerosis.

PMID- 7829285
TI  - Naltrexone attenuates the antiparkinsonian effects of picoTesla range magnetic
      fields.
AB  - Extracranial treatment with magnetic fields (MF) in the picoTesla range has been
      shown an efficacious treatment modality in the management of Parkinsonism. The
      mechanisms by which such extremely weak MF improve Parkinsonian symptoms are
      unknown. As the pineal gland has been shown to function as a "magnetosensor" and
      since exposure to various intensities of MF disrupts melatonin secretion, it has
      been proposed that the beneficial effects of MF in Parkinsonism are partly
      mediated through the actions of pineal melatonin. Animal studies indicate that
      externally applied MF also influence the activity of the opioid peptides which
      have been implicated in a broad range of pathological conditions including
      Parkinsonism. To explore whether the beneficial effects of MF in Parkinsonism
      involve the mediation of the opioid systems and following informed consent, we
      administered the opiate receptor antagonist naltrexone (50 mg, P.O.) to a
      Parkinsonian patient after he showed improvement of symptoms with application of
      MF. Results of the trial showed that naltrexone partially reversed the
      antiparkinsonian effects of MF thus suggesting that opioid peptides are involved
      in mediating the clinical effects of these extremely weak MF in Parkinsonism.
      These results also suggest that intact opioid systems may be required for a full
      expression of the antiparkinsonian effect of picoTesla range MF.

PMID- 7829286
TI  - Asymmetrical modulation of immune reactivity in left- and right-biased rats after
      ipsilateral ablation of the prefrontal, parietal and occipital brain neocortex.
AB  - We report here on the lateralized brain immunomodulation in male Wistar rats, a
      phenomenon related to the rotational bias of animal and the site of cortical
      lesion. Rats assigned to left- and right-rotators in a cylindrical Plexiglass
      rotometer were subjected to the ablation of the ipsilateral prefrontal cortex
      (PFC), parietal cortex (PC) and occipital cortex (OC) and sensitized with bovine
      serum albumin (BSA) in complete Freund's adjuvant. Intact and sham-lesioned left
      biased animals demonstrated increased Arthus and delayed hypersensitivity skin
      reactions and antibody production to BSA in comparison with corresponding right
      biased animals. PFC ablation decreased humoral and cellular immune responses to
      BSA in left- but increased in right-biased rats. Lesioning of PC decreased
      humoral immune reactions in left- but increased in right-rotating animals. OC
      ablation failed to produce immunological abnormalities. These results suggest
      that immunopotentiation is associated with the left neocortex, and
      immunosuppression with the right neocortex. The prefrontal cortex appears to be
      particularly associated with immune reactions.

PMID- 7829287
TI  - Neonatal sound stress and development of experimental allergic encephalomyelitis
      in Lewis and DA rats.
AB  - This experiment deals with the effect of neonatal sound stress on the
      susceptibility of rats in adult life to the induction of experimental allergic
      encephalomyelitis (EAE). Two inbred strains of rats, Lewis and DA, highly
      susceptible to EAE were used. On postnatal days 15, 18 and 21, animals of both
      sexes were sound stressed in a sound attenuated chamber (90dB, 60 rings/5 sec
      during 1 h, on a variable interval schedule) in the presence or absence of the
      mother. Experimental groups were as follows: (a) pups stressed without the mother
      (SP); (b) pups stressed in the presence of the mother (SPM); (c) control
      nonstressed pups separated from the mother (CP), and (d) control nonstressed pups
      undisturbed in their nest cages (CPM). Rats were weaned on postnatal day 28. At
      the age of 8 weeks, all groups were immunized with guinea pig spinal cord in
      complete Freund's adjuvant. Signs of EAE were recorded daily until the day 20
      after immunization when animals were bled and sacrificed. Serial sections of
      cerebrum, cerebellum and spinal cord were examined histologically for the
      presence of mononuclear cell infiltrates. Anti-myelin basic protein (MBP)
      antibodies were detected in serum samples using ELISA technique. Stressed Lewis
      rats (groups SP and SPM) compared to control groups CP and CPM, developed more
      severe EAE as revealed by a higher aggregate clinical score, more pronounced
      histological lesions and increased production of anti-MBP antibodies. The
      presence of the mother during stress session (group SPM) prolonged the
      disease.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7829288
TI  - Classical conditioning of pain responses.
AB  - Classical conditioning is involved in the acquisition of chronic pain. The
      present study investigated whether experimental pain responses can be conditioned
      using auditory stimuli in a differential trace conditioning paradigm. 16 healthy
      subjects served as paid volunteers. The UCS was an intracutaneous electrical
      stimulus applied to the left middle-finger (10 ms duration). Tones of 1000 and
      1400 Hz (both 80 dB SPL, 50 ms) were used as CS+ and CS-, respectively. A trace
      conditioning paradigm was used with an 800 ms interval between CS and UCS.
      Somatosensory event related potentials (SEP) and auditory event related
      potentials (AEP) were recorded from 29 electrode sites. Subjective pain reports
      were measured with an adjective list that allowed a detailed description of
      subjects' sensations elicited by painful and auditory stimuli. Data revealed
      significant differences of the subjective sensations between the CS+ and CS-, but
      no differences in the amplitudes and latencies of the P50, N100, P200, and P300
      AEP components. No changes in the topographical organization of the CS+ and CS-
      were found. A significant differential negativity in the brain sites responsible
      for processing the UCS was obtained, which is attributed to the anticipation of
      the UCS after CS+ presentation.

PMID- 7829289
TI  - The nucleus basalis of Meynert of the human brain: a Golgi and electron
      microscope study.
AB  - The nucleus basalis of Meynert of normal brains, aged from 15 to 73 years was
      studied in Golgi preparations and in electron microscopy. The nucleus is composed
      of large triangular, polyhedral and bipolar cells which are intermixed with
      numerous small or medium-sized spiny neurons. All of the neurons form a dense
      three dimensional dendritic arborization, with numerous secondary and tertiary
      dendritic branches studded with spines. The ultrastructural analysis revealed
      numerous axodendritic and axosomatic synapses between the spines. The
      ultrastructural analysis revealed numerous axodendritic and axosomatic synapses
      between the spiny neurons and the large triangular and polyhedral neurons. The
      presynaptic axonic profiles are plenty of ellipsoid and round synaptic vesicles.
      Large presynaptic terminals are seen frequently surrounded by numerous dendritic
      spines forming synaptic glomeruli, in all the areas of the nucleus basalis of
      Meynert. An age depended decrease of the number of neurons was noticed affecting
      mainly the population of the spiny neurons. Although in senile and presenile
      dementias an impressive loss of the cholinergic neurons of the nucleus basalis
      was reported, in normal aging the large cholinergic neurons of the nucleus
      basalis seems to be intact, whereas the medium and small shaped spiny neurons are
      decreased in number suggesting that the GABA-ergic neurons are principally
      affected.

PMID- 7829290
TI  - Central cardio-autonomic disorganization in interictal states of epilepsy
      detected by phase space analysis.
AB  - In a study of central autonomic organization in interictal states of idiopathic
      generalized epilepsy, we measured the spontaneous oscillations of the heart rate
      in 8 young epileptics with normal interictal electroencaphalograms (EEGs), 6
      young epileptics with epileptiform discharges in the interictal EEGs and 8
      healthy controls. The temporal structure of the heart rate (HR) dynamics was
      operationalized through the estimation of the largest Lyapunov exponent (LLE).
      For all patients and controls, the LLEs of the HR dynamics were positive,
      indicating chaotic oscillations. The patients with interictal epileptiform
      discharges showed significantly lower LLEs of the HR dynamics than the epileptics
      with normal EEGs and the healthy controls. By comparison, the values of the
      epileptics with normal EEGs und those of the healthy controls did not differ
      significantly. This finding suggests a more rigid and thus less adaptable central
      cardio-autonomic organization in epileptics with epileptiform discharges in the
      interictal EEG.

PMID- 7829291
TI  - Decrease of serum iron in acutely psychotic schizophrenic patients.
AB  - Iron deficiency has been shown to effect the dopaminergic system. Iron deficient
      rats have low dopamine D2 receptor levels and modified dopamine-mediated
      behaviors, including reversal of circadian cycles of these behaviors. Abnormal
      iron deposits have been found in the brains of schizophrenics in CT and post
      mortum studies. We examined serum iron levels at 0800, 1700 and 2400 hours in 26
      medication free schizophrenic patients in acute psychotic relapse and compared
      them to iron levels in a normal control group. The results show significant
      decreases in the iron levels at 1700 and 2400, and a non significant drop in the
      0800 levels. A feedback mechanism involving iron and dopamine is proposed.

PMID- 7829292
TI  - Improvement by picoTesla range magnetic fields of perceptual-motor performance
      and visual memory in a patient with chronic progressive multiple sclerosis.
AB  - The occurrence of cognitive deficits in multiple sclerosis (MS) has been
      recognized since 1877 when Charcot first observed "enfeeblement of memory." It is
      now recognized that visuoperceptive and visuomotor deficits commonly occur in MS
      patients particularly in those with a chronic progressive course of the disease.
      Using various drawing tests as markers of constructional performance, we reported
      recently that treatment with picoTesla range magnetic fields (MF) rapidly
      improved visuoperceptive and constructional abilities in patients with MS. We now
      report a 58 year old man with a 37 year history of chronic progressive MS in whom
      external application of MF in the picoTesla range produced rapid improvement of
      neurologic symptoms including walking, balance, sensory symptoms, and bladder
      functions. The patient's recovery was associated with a significant improvement
      in perceptual-motor functions as demonstrated on the Rey-Osterrieth Complex
      Figure and the Trail Making tests. Specifically, the patient demonstrated a 41%
      improvement over pretest values on copying the Complex figure and a 72%
      improvement in recall of the figure immediately after MF treatment. A further 4%
      improvement on copying the figure and a 27% improvement on recall was
      demonstrated 24 hours later. On the Trail Making test the patient demonstrated an
      overall improvement of 39% in Part A of the test and a 24% improvement in Part B
      of the test 24 hours after application of MF. These findings confirm the
      beneficial effects of picoTesla range MF in the treatment of MS and demonstrate
      the unique efficacy of this treatment modality in improving some of the cognitive
      deficits of the disease.

PMID- 7829293
TI  - Serotonergic and serotonin-synthesizing cells of the Xenopus retina.
AB  - It has been shown previously that a subclass of OFF-center bipolar cell in the
      Xenopus retina contains endogenous serotonin which can be released upon
      depolarization in a calcium-dependent manner. Based on single- and double
      labeling immunocytochemical experiments, this study provides evidence that these
      bipolar cells acquire their "endogenous" serotonin from another retinal source.
      The primary source in the Xenopus retina are large soma amacrine cells which are
      the only cellular elements containing the necessary enzymatic pathway for
      serotonin synthesis.

PMID- 7829294
TI  - Dopamine mechanisms of cocaine addiction.
AB  - The ability of cocaine to induce a compulsive addictive behavior is the most
      astonishing feature of this drug. Attempting to understand the mechanisms
      underlying cocaine's addictive properties, two major questions should be
      considered: a) why and how organism's interaction with cocaine results in the
      development of new, drug-seeking and drug-taking behavior and b) why and how
      cocaine maintains this behavior when the drug is available. Since a large body of
      neuropharmacological evidence suggest that the mesocorticolimbic dopamine (DA)
      system has exclusive importance for the development and maintenance of cocaine
      addictive behavior, and cocaine is known to interfere in activity of this brain
      system, examination of mesocorticolimbic DA activity during cocaine self
      administration behavior may provide some clues for understanding the drug's
      additive properties and regulation of this maladaptive goal-directed behavior.
      The aim of this paper is to discuss the literature and own experimental data on
      cocaine's action on the mesocorticolimbic DA system that may be involved in
      mediating its addictive properties. Based on these data, it is suggested that an
      inhibiting action of cocaine on reuptake of released DA, although essential, but
      not sufficient mechanism for the development and maintenance of addictive
      behavior. It is hypothesized, that coexistence of functionally antagonistic,
      inhibiting actions of cocaine on the mesolimbic DA release and reuptake of
      released DA may be responsible for biphasic fluctuations in DA transmission that
      appear to be a critical component of central oscillatory mechanism which drives
      and regulates cyclic drug-taking behavior.

PMID- 7829295
TI  - Disorders of verbal and pictorial memory in right and left brain-damaged
      patients.
AB  - It is still controversial whether verbal and pictorial stimuli are independently
      processed and stored in memory, as assumed by the dual code hypothesis, or a
      single code is used both for verbal and for pictorial stimuli, as assumed by the
      verbal loop hypothesis and by the propositional code hypothesis. According to the
      first hypothesis, verbal and pictorial memory are independently disrupted by
      brain damage, whereas according to the second hypothesis a co-occurrence of
      verbal and pictorial memory disorders are usually observed. To test these
      contrasting predictions, we constructed a verbal and a pictorial memory task very
      similar with respect to testing procedures and to material to be memorized and we
      administered them to 33 left and 27 right brain-damaged patients and to 21 normal
      controls. The following results were obtained: 1) Disorders of verbal and of
      pictorial memory were dissociated by brain injury in about one-third of our
      patients; 2) A consistent relationship was observed between laterality of lesion
      and type of selective memory impairment, since word recognition was selectively
      impaired by left and picture recognition by right brain injury; 3) However, only
      on the test of verbal memory was a significant difference between right and left
      brain-damaged patients obtained, whereas on the test of pictorial memory only a
      nonsignificant trend in the opposite direction was observed. These data are in
      favor of the dual code hypothesis and suggest that the links between left
      hemisphere and verbal code may be stronger than the relationship between right
      hemisphere and pictorial code.

PMID- 7829296
TI  - Nurses updated on HIV/AIDS research at ICN conference.

PMID- 7829297
TI  - Japan: HIV/AIDS epidemic galloping ahead.

PMID- 7829298
TI  - HIV/AIDS and human rights.

PMID- 7829299
TI  - Tuberculosis, HIV on collision course.

PMID- 7829300
TI  - Getting the community involved in developing a PHC curriculum in Tonga.
AB  - To be relevant and effective, a nursing curriculum must reflect societal needs,
      health and community structures and resources. Below is a case study of a
      contractual collaboration between various stakeholders in a post-graduate
      programme based on primary health care in public health nursing in Tonga. It is
      one example of the influence and collaborative roles that communities play in the
      health of people.

PMID- 7829301
TI  - Nurse-managed centres: an innovative structure for nursing education and care.
AB  - The development of nursing centres in the USA began in the late 1800s with the
      concept of community-based nursing care provided by district and visiting nurses.
      Primary roles included health promotion and safeguarding hygiene in addition to
      caring for the sick. Established in 1893, the Henry Street Settlement in New
      York, a public health nursing system providing direct access to health care,
      became a model for other agencies in the USA.

PMID- 7829302
TI  - Planning a community nursing centre.
AB  - The poor, elderly, single parents and other vulnerable groups have had limited
      options in receiving affordable, comprehensive and culturally sensitive care.
      Today, this gap is being filled by nurse-managed centres in accessible areas
      offering primary care to communities, particularly the underserved. Below, the
      planning, development and implementation of one such nursing centre.

PMID- 7829303
TI  - Family nursing in community-oriented primary health care.
AB  - Renowned for its innovative approach to community health promotion and the key
      role of the nurse in treatment, prevention, teaching and research, the Philip and
      Sally Lown Hadassah Community Health Centre in Jerusalem is a model where the
      nurse is a member of a comprehensive multidisciplinary team that comprises family
      and paediatric physicians, epidemiologists, psychologist, statistician, social
      worker, health educator, health recorder, dietician and other public health
      specialists. As such, the nurse actively participates in the planning,
      implementation and evaluation of all new programmes, improvements and policy
      changes. Below, how the nurse works as a team member in the community centre.

PMID- 7829304
TI  - Family decisionmaking and forgoing treatment: a judicial perspective.

PMID- 7829305
TI  - Informed consent: from the ambivalence of Arato to the thunder of Thor.

PMID- 7829306
TI  - Competency to refuse lifesaving treatment: valuing the nonlogical aspects of a
      person's decisions.

PMID- 7829307
TI  - Christian Science healing of minor children: spiritual exemption statutes, first
      amendment rights, and fair notice.

PMID- 7829308
TI  - When life becomes optional: a comment on Kevin O'Rourke's approach to forgoing
      life support.

PMID- 7829309
TI  - In re Michael Martin.

PMID- 7829310
TI  - Phospholipid base-exchange in brain microvessels.
AB  - The capillary endothelium of cerebral microvessels plays an important role in
      homeostasis within the central nervous system. The flux of fluids and solutes
      takes place through the lipid matrix of plasma membranes and the maintenance of
      their structural composition is necessary for cell membrane permeability and the
      cellular transport systems. Few studies have been carried out to clarify the
      relationships between brain microvessel lipid metabolism and the role of this
      metabolism. We have studied a particular aspect of the phospholipid metabolism,
      i.e. their hydrosoluble head group exchange with free choline, ethanolamine or
      serine, in capillaries from brains of both 4 month- old and 24 month-old rats.
      The results obtained indicate that microvessels possess the biochemical machinery
      of base-exchange reaction, whose activity rate appears unaffected by age.

PMID- 7829311
TI  - Mental health of rural elderly: a research agenda for nursing.
AB  - Only recently have the health sciences, including nursing, begun to focus on the
      dynamics of mental health and aging. Reports on rural initiatives, are beginning
      to appear; these developments have occurred without the benefit of context and
      direction, however, especially in terms of how these issues apply in rural areas.
      The article reviews selected issues in the interface of aging and mental health
      in rural areas. It offers a research agenda comprising descriptive, intervention,
      and utilization studies as a context to guide research and knowledge development
      in mental health nursing of rural elderly.

PMID- 7829312
TI  - Use of substitute decision makers by the mentally ill rural elderly: an issue of
      concern for mental health nurses.
AB  - In 1986, the Abbe Center for Community Mental Health implemented a nurse-led
      elderly outreach program (EOP) designed to identify and treat elderly rural
      residents in need of mental health care. Because some EOP clients evidenced a
      lack of or limited decision-making capacity, a record review was conducted to
      answer the following questions: Do any of the clients have a legal substitute
      decision maker? What are the forms of substitute decision making? Is there a
      familial relationship between the elderly client and the substitute decision
      maker? Is there evidence that any of the named legal substitute decision makers
      have abused the elder? Almost half the clients who had a substitute decision
      maker used a power of attorney. Adult children were the most frequent family
      members named as substitute decision makers. Four records indicated that an adult
      child had been given a power of attorney and that the child had potentially
      abused the parent. Implications for mental health nurses dealing with this
      vulnerable population are set forth.

PMID- 7829313
TI  - Mental health clinical nurse specialist in home care for the 90s.
AB  - The role of the mental health clinical nurse specialist (CNS) in home care is
      explored in light of the changing emphasis on health care reform. Home care is a
      field that will continue to expand in the future, and the role of the CNS takes
      on new definition by addressing the physical and mental health needs of the
      chronically mentally ill in the community as well as those of the population of
      clients and families dealing with psychosocial crises, where early discharge
      leaves them particularly vulnerable. The emphasis is seeing the CNS in home care
      as a key point of entry and intervention in the mental health delivery system
      with a focus on prevention and wellness care. Collaborative aspects of care with
      health care providers and consumers are discussed through case examples.
      Reimbursement issues are framed within current health regulations with continued
      changes evolving within the health care reform movement.

PMID- 7829314
TI  - Wellness education for individuals with chronic mental illness living in the
      community.
AB  - The article reports a wellness education program developed to enhance and promote
      healthy life-style behaviors for individuals with chronic mental illness living
      in the community. Theoretical concepts from health promotion, wellness, and
      social learning were used in the development of this program. The program
      comprised three components: wellness education sessions, exercise/activity
      sessions, and a smoking reduction course.

PMID- 7829315
TI  - When your client lives in a rural area. Part I: Rural health care delivery
      issues.
AB  - In the past 2 years there has been increased emphasis on health care delivery
      concerns in rural environments. Research monies also target the health care needs
      of vulnerable populations living in areas with a shortage of health
      professionals; many of these populations are located in rural areas. There is,
      however, a paucity of information about populations and mental health nursing in
      rural environment. Part I of this two-part article summarizes pertinent
      definitions and characteristics of rural environments. The health care delivery
      system in rural settings is considered within a framework of availability,
      accessibility, and acceptability of services. Traditional belief systems are
      highlighted, and the impact of these on health care-seeking behaviors of rural
      people are discussed.

PMID- 7829316
TI  - When your client lives in a rural area. Part II: Rural professional practice-
      considerations for nurses providing mental health care.
AB  - Part I of this two-part article examined the rural health care delivery system
      within the framework of availability, accessibility, and acceptability of
      services. Traditional rural values were explored in relation to ruralities'
      health care-seeking behaviors, specifically mental health care. Part II
      highlights the opportunities and challenges of rural professional practice,
      particularly as they apply to nurses caring for those with emotional problems who
      need mental health services. Strategies are suggested to enhance the continuum of
      care for clients who live in environments with sparse resources.

PMID- 7829317
TI  - Operationalizing Maslow's theory: development and testing of the basic need
      satisfaction inventory.
AB  - Although Maslow's theory is frequently cited in the nursing literature and is
      commonly used as an underlying framework for clinical practice, it has been
      subjected to limited empirical scrutiny. This may be due, in part, to a scarcity
      of survey measures to operationalize the construct of need satisfaction. The
      Basic Need Satisfaction Inventory (BNSI) was developed for this purpose. The
      instrument, created from Andrews and Withey's indicators of life concerns and
      their "delighted-terrible" scale, was first examined through secondary data
      analysis, pilot tested (N = 21), and then administered to samples of men and
      women with chronic pulmonary disease (N = 109) and healthy older adults (N =
      100). Emerging evidence of internal consistency reliability and construct
      validity suggests that the BNSI may be a useful instrument to measure need
      satisfaction and to test the adequacy of Maslow's theory for nursing science and
      practice.

PMID- 7829318
TI  - State university collaboration to transform practice in public sector psychiatric
      nursing.
AB  - In 1986 and again in 1988, Hawaii was ranked by the Torrey report as being 51st
      in the nation in caring for its persistent and seriously mentally ill. After
      several years of being ranked last in the nation, and with the threat of a
      consent decree from the U.S. Department of Justice, the state of Hawaii made a
      commitment to improve the psychiatric mental health care of its citizens. The
      state's Department of Health, in September 1990, contracted with the University
      of Hawaii's School of Nursing to provide joint appointment faculty to consult
      with the nursing staff and to provide the department's chief of nursing. Working
      together with the joint appointment faculty, the permanent staff began the
      journey toward creating a state-of-the-art facility. The article discusses how
      change of such magnitude has been created.

PMID- 7829319
TI  - Codependence: contextual variables in the language of social pathology.
AB  - The concept of codependence is examined. The history of the term is reviewed, and
      definitions from the current literature are given. Characteristics of
      codependence are listed, including denial, control, difficulty in trusting, low
      self-esteem, weak boundaries, and overreponsibility. Theories concerning the
      genesis of this condition are described. Problems with the concept are detailed,
      and questions for further study are generated. The conclusions support the need
      for caution in labeling and for recognizing the potential for misusing concepts
      that are in the early stage of development.

PMID- 7829320
TI  - Environmental characteristics related to patient assault.
AB  - Environmental factors related to physical assault by patients were examined to
      identify clinical implications warranting further investigation and to test
      methodology. The concepts of ward conditions (degree of patients' illness,
      numbers of patients and staff) and ward climate were the focus of the study.
      Participants were patients and nursing staff on two acute and four long-term
      psychiatric units in a large neuropsychiatric hospital. Patients and staff were
      asked to complete the Ward Atmosphere Scale to assess ward mood and climate. Each
      assault incident was identified from the daily nursing ward report. With each
      assault occurrence, the nurse manager was asked to complete a questionnaire about
      environmental conditions at the time of the assault. Most assaults occurred
      during meal times and afternoons. The most frequent locations were ward corridors
      and dayrooms. There appeared to be an inverse relationship between assault
      frequency and number of staff. Crowding rather than total number of patients per
      ward was suggested as a factor related to assault. Degree of patient acuity
      seemed to be inversely related to assault frequency. There were suggested trends
      between assault frequency and a low score on autonomy and a high score on staff
      control. Clinical implications, ideas for further research, and improved design
      measures are suggested. The challenge to understand and control this complex
      phenomenon remains a critical issue for inpatient nursing care.

PMID- 7829322
TI  - Staffing: cause for concern.

PMID- 7829321
TI  - Gone with the wind?

PMID- 7829323
TI  - Taking up the sales challenge.

PMID- 7829324
TI  - Sick housing syndrome.

PMID- 7829325
TI  - Educating teachers about asthma.

PMID- 7829326
TI  - Managing childhood asthma: the health visitor's role.
AB  - Most health visitors working in Britain today will have a number of children in
      their workload who are asthmatic. Parents and sufferers are often anxious to
      obtain more information to help their understanding and management of the
      condition. Doreen Deaves describes the results of a study which indicate that
      health visitors are ideally placed to provide health education and support for
      parents and families of children with asthma.

PMID- 7829327
TI  - Education. Nursing by degrees.
AB  - It is quite clear in PREP that community nurses will still be able to practice,
      whether their current qualification was at certificate or diploma level. However,
      future community nurse courses will be at degree level and many nurses who are
      currently practising are concerned that they too should have a degree. Sarah
      Forester provides brief guidance for community nurses who are considering further
      academic study.

PMID- 7829328
TI  - Working together to meet the needs of multiple-birth families.
AB  - Health visitors have an important role in providing postnatal support to multiple
      birth parents, write Jill Walton et al. Here they describe how a series of joint
      parent/professional seminars helped raise awareness among health visitors of the
      special needs of multiple-birth parents for services and support, and the
      importance of developing closer links with voluntary and self-help groups at
      local and national level.

PMID- 7829329
TI  - Doing through speech: the health visitor's skill.
AB  - Health visitor training demands a radical change in outlook. Nurses and midwives,
      coming from a practical, 'hands-on' approach, face a major professional re
      orientation in order to work principally through the medium of language.
      Katherine Brettell uses the theory of 'speech acts' to explore and explain the
      process of health visiting, demonstrating the need for practitioners to be highly
      skilled communicators.

PMID- 7829330
TI  - Early identification of communication problems.
AB  - Questions have been raised about the effectiveness of routine early screening of
      children's speech development. Mary Gale et al describe an innovative package
      which can be used by health visitors and parents to ensure they correctly
      identify those children needing referral for specialist intervention.

PMID- 7829331
TI  - Tuberous sclerosis: how to recognise this challenging disorder.
AB  - Tuberous sclerosis is a multi-system genetic disorder affecting up to one in 6000
      newborn infants. It is about one third as common as cystic fibrosis, and half as
      common as Duchennes muscular dystrophy, yet many doctors and health professionals
      are ill-acquainted with the condition. Parents who turn to medical text books for
      information find only a brief mention of a few, frequently out-dated facts.
      Antonia Clarke and John Osborne describe the symptoms of the disorder and the
      special needs of affected children and their families.

PMID- 7829332
TI  - Defining our terms: community development and public health.
AB  - The HVA's community development interest group was launched to provide a forum
      for health visitors working, or wishing to develop their work, in this specialist
      area of practice. Ian Brown reflects on the discussions and issues raised at a
      study day organised by the group in March this year.

PMID- 7829333
TI  - Integrating a community development approach with mainstream health visiting.
AB  - Community development work is often seen as an activity separate from and working
      to different principles to traditional health visiting practice. Yvonne Dalziel
      describes how, required by management to take on a routine health visiting
      caseload, she is attempting to integrate the community development approach to
      her work with families and children.

PMID- 7829334
TI  - Support for families with children with special needs.
AB  - Families with children with special needs have to cope not only with their
      child's condition, but also with practical problems such as transport and
      opportunities for a break from their caring responsibilities. Anthea Clarke
      describes how 'Flexicare' helps these families in Oxfordshire, and calls for more
      such voluntary groups across the country.

PMID- 7829335
TI  - Childcare review may offer hope.

PMID- 7829336
TI  - Asking why and saying no.
AB  - A change of atmosphere in the NHS has left many staff less prepared to challenge
      management decisions. This is partly reflected in reports of increased bullying
      at work and of the risks of being a whistleblower. Yet much grief in the NHS (and
      elsewhere) would be avoided if staff were a little more assertive when decisions
      affecting them are being taken. Often simple steps can help avoid more difficult
      situations later on. Roger Kline looks at some common situations and how to
      negotiate your way through them.

PMID- 7829337
TI  - Quango mania: time to find a cure.

PMID- 7829338
TI  - Look behind you...

PMID- 7829339
TI  - Grimethorpe. Survival strategies.

PMID- 7829340
TI  - Coma report. Best practice in infant feeding.

PMID- 7829341
TI  - Sleep management. Evaluating advice booklets for parents.
AB  - Health professionals are increasingly using information booklets to disseminate
      important health messages to a wider population. However, such booklets are
      rarely evaluated from the consumer's point of view. Robert Deller and Jo Walker
      describe an evaluation by parents of a series of booklets giving parents advice
      about dealing with sleep problems in young children.

PMID- 7829343
TI  - Talk about teeth.
AB  - In the designated Year of Oral Health, John Spencer examines the importance of
      design to effective oral health promotion through use of leaflets, posters and
      other visual media, and points to some omissions.

PMID- 7829342
TI  - How readable are health education leaflets?
AB  - Leaflets are a comparatively cheap and potentially effective way of conveying
      health information, but how successfully do they get their message across? John
      Ormrod and Michelle Robinson tested some widely-produced examples for
      readability.

PMID- 7829344
TI  - Balancing workloads under GP attachment.
AB  - Alignment with a GP practice resulted in fluctuating workloads for health
      visitors Lynda Brooks, Caro Fickling and Caroline Walker. Here they describe how
      the introduction of a corporate caseload helped to restore balance.

PMID- 7829345
TI  - Why another leaflet?
AB  - Mary Rutledge and Joanne Davis explain why they produced a leaflet to promote
      healthy eating to children at school. Liz Bixby describes a leaflet on
      bronchiolitis, which won the HVA award at this year's annual professional
      conference.

PMID- 7829346
TI  - Access to library services.
AB  - To develop as a profession, nursing needs a credible academic education base. Yet
      access to library facilities is limited. Patrick Davies suggests a political
      motive: the deliberate holding back of a predominantly female profession.

PMID- 7829347
TI  - Primary care. Facilitators: looking forward.
AB  - The role of the primary care facilitator has developed rapidly and has much in
      common with that of the health visitor. Rosemary Cook looks at its beginnings and
      assesses its future place in practice-based primary care.

PMID- 7829349
TI  - Voluntary allies.

PMID- 7829348
TI  - Setting standards for a school nursing service.
AB  - School nurses in Airedale have developed a set of standards and procedures for
      their service using British Standard BS 5750* as a framework. Liz Lloyd et al
      describe this innovative approach to achieving an effective, client-responsive
      quality management system.

PMID- 7829350
TI  - Income support. Shifting sands of social insecurity.
AB  - The 1988 Social Security Act and subsequent tinkering with the means-tested
      benefits system has made no difference at all to overall poverty levels. Beth
      Lakhani reviews the changes since 1988, and predicts more of the same--only
      worse.

PMID- 7829351
TI  - Maternity rights. Watered down.
AB  - In line with the changes to statutory maternity leave and pay, introduced in
      October, the General Whitley Council has issued new arrangements for NHS staff.
      The HVA believes that the revisions to section six of the GWC handbook sell women
      short, and in some instances offer them less than the statutory minimum. Kate
      Bennett outlines the shortcomings, and highlights the key issues for local
      bargaining.

PMID- 7829352
TI  - A vision for today.

PMID- 7829353
TI  - Older people. Pass the parcel.

PMID- 7829354
TI  - Ecology. No future?

PMID- 7829355
TI  - Not a pretty picture.

PMID- 7829356
TI  - Information. Counting what counts.
AB  - The NHS changes are highlighting the need for the collection of meaningful data
      in the community health services, writes Wendy King. She describes how health
      visitors can help supercede the simplifications of Korner statistics by helping
      the NHSE's information management group to devise systems which count what really
      counts.

PMID- 7829357
TI  - Commissioning for health.
AB  - The NHS internal market offers community nurses unprecedented opportunity to
      achieve, through influencing the purchasing process, real improvements in health
      and health care. Shirley Goodwin outlines what she, as a purchaser, looks for
      when she commissions community nursing services.

PMID- 7829358
TI  - Opportunities for health in contracting.
AB  - Contracts are about much more than the simple purchasing of services. In an NHS
      context, they are also about working in partnership with patients, and about good
      employment practices, writes Judy Hargadon. Here she outlines how contracts can
      be used to improve health care services, and the health of those involved in both
      receiving and providing that care.

PMID- 7829359
TI  - Professional leadership in community nursing services.
AB  - To community nurses experiencing the chaos of repeated organisational change, the
      NHS can seem an environment hostile to clinical excellence. But, writes Alison
      Norman, the changing nature of health service management offers new opportunities
      for health visitors and school nurses to take the lead in pushing forward the
      boundaries of clinical practice. Here she examines the concept of leadership, and
      challenges practitioners to take up the gauntlet.

PMID- 7829360
TI  - Professional accountability: the path to empowerment.
AB  - Pippa Gough argues that practitioners should exercise their professional
      accountability and competence to the full in order better to meet the needs and
      serve the interests of their patients and clients--and to establish nursing's
      rightful place at the centre of the health care world.

PMID- 7829361
TI  - The road to the courts.
AB  - Nurses and health visitors are professionally accountable for their standards of
      practice, but they can also be called to account for their actions or omissions
      before a civil or criminal court. Andrew Andrews explains how the legal process
      operates when nurses and health visitors are accused of professional malpractice.

PMID- 7829362
TI  - Clinical supervision.
AB  - Since the publication, in April 1993, of A vision for the future, clinical
      supervision has become a major topic of debate within the nursing, midwifery and
      health visiting professions. Here the Health visitors' association provides an
      overview of the present discussions, offering a range of definitions of the term,
      together with information on the general principles of supervision and the
      requirements for its effective implementation. The final section lists a range of
      questions useful for members to raise and discuss when the introduction of
      clinical supervision is being planned.

PMID- 7829363
TI  - The market is the message.

PMID- 7829364
TI  - Burning issues of safety.

PMID- 7829365
TI  - Under five and under paid: the mobility-related costs of disabled children under
      five.

PMID- 7829366
TI  - Clients come first.
AB  - Professional accountability is central to all nursing and health visiting
      practice. Roger Kline explains how this operates in the context of skill mix and
      challenging excessive workloads.

PMID- 7829367
TI  - Genetic engineering.

PMID- 7829368
TI  - Essex girl. Interview by Catherine Jackson.

PMID- 7829369
TI  - Special needs. Sharing the cares.

PMID- 7829370
TI  - Georgia veterinarians rise above flood crisis.

PMID- 7829371
TI  - Teaching dental procedures.

PMID- 7829372
TI  - Positions of meat animal producers.

PMID- 7829373
TI  - Working with veterinary editors.

PMID- 7829374
TI  - What is your diagnosis? Pericardial effusion in a cat.

PMID- 7829375
TI  - Use of a primary muscle pedicle flap to repair a caudal thoracic wound in a
      horse.

PMID- 7829376
TI  - Platelet concentration and hemoglobin function in greyhounds.
AB  - Hematologic characteristics of 36 Greyhounds were studied and compared with
      characteristics of 22 non-Greyhound controls. Fourteen of the Greyhounds were
      tested and found to be seronegative for Ehrlichia canis and Babesia canis.
      Compared with the non-Greyhounds, Greyhounds had higher mean hemoglobin
      concentration, PCV, mean corpuscular volume, and mean cellular hemoglobin, and
      lower mean RBC count, hemoglobin P50 value, Hill coefficient, platelet count, and
      total plasma protein concentration. The lower mean hemoglobin P50 value in
      Greyhounds suggested that the higher mean hemoglobin concentration and PCV were
      not solely a result of selective breeding for superior racing abilities, but that
      Greyhound hemoglobin may have a greater affinity for oxygen than does the
      hemoglobin of non-Greyhounds.

PMID- 7829377
TI  - Decreased urinary catecholamines in a cat with dysautonomia.
AB  - Feline dysautonomia was diagnosed in a 2-year-old cat with a history of
      regurgitation, constipation, mydriasis, and dry eyes. The diagnosis of
      parasympathetic and sympathetic failure was confirmed by abnormal physiologic
      autonomic function tests and decreased urinary catecholamine measurements.
      Despite intensive supportive care, the cat failed to improve and was euthanatized
      70 days after the onset of illness. Feline dysautonomia is rarely reported in the
      United States, and the cat had no history of travel to a country where the
      disease is more prevalent.

PMID- 7829378
TI  - Chondrodysplasia in five Great Pyrenees.
AB  - Five disproportionate, short-limbed, short-trunked (dwarf) Great Pyrenees pups
      were examined. The mode of inheritance was compatible with a simple autosomal
      recessive trait, and skeletal radiography revealed flaring of the metaphyses of
      all long bones and the costochondral junctions of the ribs. Vertebral bodies were
      poorly ossified and short, and had a beak-like extension on the caudal
      metaphyseal margin. Vertebral body end-plates were thin and concave, and
      ossification was abnormal. Three of the 5 dogs were deaf, and 1 had testicular
      atrophy. Ocular examinations did not reveal any abnormalities. Histologic
      examination of the growth plates revealed disorganized chondrocyte columns, and
      chondrocytes appeared to have undergone degenerative changes in the zone of
      chondrocyte proliferation. Transmission electron micrography of growth plate
      chondrocytes revealed dilated profiles of rough endoplasmic reticulum.

PMID- 7829379
TI  - Hyperferritinemia associated with malignant histiocytosis in a dog.
AB  - A 3.5-year-old male Golden Retriever with lethargy, generalized lymphadenopathy,
      and hepatosplenomegaly was determined to have malignant histiocytosis, based on
      the morphologic appearance of neoplastic cells by light and electron microscopic
      examination, evidence of erythrophagocytosis, the presence of diffuse nonspecific
      esterase activity, and immunohistochemical demonstration of vimentin intermediate
      filaments. Because of the appearance of abundant iron stores in the bone marrow,
      serum was obtained for determination of iron, total iron binding capacity, and
      ferritin values. Serum ferritin concentrations were markedly increased.
      Measurement of serum ferritin concentrations may be useful in supporting a
      diagnosis of malignant histiocytosis, and the monitoring of serum ferritin
      concentrations may be useful for assessing treatment and regression of the
      disease.

PMID- 7829380
TI  - Treatment of acute lead ingestion in a juvenile macaw.
AB  - A juvenile domestic green-winged macaw was admitted to the veterinary clinic
      within an hour of ingestion of lead drapery weights. Radiopaque objects were
      evident in the crop and ventriculus. The bird was anesthetized, and the crop was
      lavaged to remove lead fragments. Because lead fragments remained in the
      ventriculus after lavage, chelation treatment was instituted. Serial radiography
      was done on days 2, 5, 9, and 14 to determine passage of the lead. By day 14,
      lead fragments were not visible radiographically. The macaw did not have ill
      effects from the lead ingestion or from medical treatments. Because this bird had
      been observed ingesting the lead weights, treatment was for foreign body
      ingestion initially and for lead ingestion secondarily.

PMID- 7829381
TI  - Risk factors for behavior-related euthanasia among dominant-aggressive dogs: 110
      cases (1989-1992).
AB  - Establishing a prognosis for dogs with dominance-related aggression is difficult.
      Some dominant-aggressive dogs respond well to treatment; others continue to be
      serious risks for their owners. A study was performed to identify characteristics
      of dominance-related aggression and to identify risk factors associated with
      whether the aggressive behavior led to euthanasia. Medical records of 110 dogs
      with dominance-related aggression were examined retrospectively; characteristics
      of owner-directed aggression and eventual outcome of the dogs were recorded. By
      means of logistic regression, 2 different models were found to describe the
      association between behavior characteristics and outcome. In the first model,
      severe aggression in response to benign dominance challenges and body weight >
      18.2 kg were associated with outcome. In the second model, unpredictability of
      aggression and a history of being purchased were associated with outcome. We
      concluded that dominance-related aggressive behavior can be subclassified
      according to severity and type and that outcome (ie, euthanasia) may be
      predictable in some cases.

PMID- 7829382
TI  - Lead foreign body arthropathy in a horse.
AB  - A diagnosis of degenerative joint disease secondary to an intra-articular
      metallic foreign body in the right metacarpophalangeal joint was made in a
      Quarter Horse gelding. Arthroscopy, performed to evaluate the joint and remove
      the foreign body, revealed yellow discoloration of the articular cartilage and
      synovium, and blunting and proliferation of the synovium. The foreign body was
      identified as a lead sphere. Microscopic examination of synovium revealed chronic
      synovitis, with accumulation of hemosiderin and multifocal, mild mineralization.
      Another pigment was evident extracellularly in the synovium. Lead arthropathy was
      diagnosed. Lead arthropathy results from the dissolution of intra-articular lead,
      causing signs of chronic pain, restricted motion, joint effusion, and synovial
      proliferation.

PMID- 7829383
TI  - Stringhalt secondary to trauma to the dorsoproximal region of the metatarsus in
      horses: 10 cases (1986-1991).
AB  - A review of medical records was used to identify 10 horses in which stringhalt
      developed subsequent to trauma to the dorsal metatarsus. Six horses developed
      stringhalt within 3 months after injury, 3 horses developed stringhalt > 3 months
      after injury, and time from injury to stringhalt was unknown for 1 horse. Horses
      were treated with exercise, including daily hand-walking with pasture turnout,
      followed by lunging; or surgically, using lateral digital extensor myotenectomy.
      Of the horses treated with exercise, 1 had resolution of stringhalt, 2 improved
      but had residual stringhalt, and 1 had no change. Two of the horses having
      lateral digital extensor myotenectomy had resolution of stringhalt. Two of the
      remaining 3 horses treated surgically had varying degrees of improvement, and in
      1 horse there was no change. Stringhalt is a potential complication following
      trauma to the dorsal metatarsal region. Potential causes include tendon adhesions
      enhancing tarsocrural joint flexion or abnormalities in the myotatic reflex
      caused by tendon injury that result in abnormal flexion of the tarsocrural joint.

PMID- 7829384
TI  - Effect of exogenous prostaglandin F2 alpha in clinically normal postparturient
      dairy cows with a palpable corpus luteum.
AB  - In 228 clinically normal cows with a palpable corpus luteum 20 to 40 days after
      parturition and a mean 305-day mature equivalent milk production of 8,970 kg,
      prostaglandin F2 alpha was administered in a randomized, controlled clinical
      trial to determine whether such treatment enhanced their subsequent reproductive
      performance. Although the treatment reduced median time to first breeding by 4.5
      days (P = 0.0025) from 57.0 days, median time to conception was not significantly
      different between the treatment and nontreated control group (87.0 vs 88.5 days)
      and conception rate by 110 days after parturition was not significantly different
      (64.7 vs 69.6%). Use of prostaglandin was associated with a significant (P =
      0.0459) decrease in conception rate at first breeding from 42.0 to 29.3%. This
      study suggested that prostaglandin treatment of cows with a normal reproductive
      tract and a palpable corpus luteum at a median of 25 days after parturition does
      not enhance their reproductive performance and thus is not cost-effective.

PMID- 7829385
TI  - Vesicular adenitis syndrome in beef bulls.
AB  - Vesicular adenitis syndrome was diagnosed in 69.3% (52/75) of a group of yearling
      bulls on breeding soundness examination. Association of Haemophilus somnus
      infection with vesicular adenitis syndrome was confirmed in these bulls by
      microbial culture of vesicular gland fluid or semen samples and serologic
      testing.

PMID- 7829386
TI  - Postural radiography in dogs.

PMID- 7829387
TI  - DMAB-induced rat invasive prostatic carcinomas.

PMID- 7829388
TI  - Cancer mortality in low radon spa area.
AB  - Recently lower mortality for cancers of all sites was reported among inhabitants
      in the Misasa spa area, where there is a high radon background. To clarify the
      effects of radon exposure on cancer mortality, the effects of a hot spring itself
      on cancer mortality was investigated in the Beppu spa area, which has only a low
      radon background, and adjacent control areas. For females, the mortalities for
      cancers of all sites, liver and lung were higher in Beppu than those for all
      Japan on the basis of the standardized mortality ratio (SMR), while the SMR for
      all cancers was lower in adjacent areas. For the male inhabitants in both areas
      the cancer mortalities of all sites were not significantly different from those
      of all Japan. When we directly compared the most typical spa areas in Beppu and
      an adjacent control area, a Poisson regression analysis did not show that the
      relative risk of dying from cancer of all sites was decreased in the spa areas.
      These results are thus consistent with the view that the lower cancer mortality
      in the Misasa spa area might be related to exposure to low levels of radon.

PMID- 7829389
TI  - Enhancing effects of organosulfur compounds from garlic and onions on
      hepatocarcinogenesis in rats: association with increased cell proliferation and
      elevated ornithine decarboxylase activity.
AB  - Four organosulfur compounds from garlic and onions were examined for modifying
      effects on diethylnitrosamine (DEN)-induced neoplasia of the liver in male F344
      rats using the medium-term bioassay system based on the two-step model of
      hepatocarcinogenesis. Carcinogenic potential was scored by comparing the numbers
      and areas per cm2 of induced glutathione S-transferase placental form-positive
      foci. Isothiocyanic acid isobutyl ester (IAIE), dipropyl trisulfide (DPT), and
      allyl mercapton (AM) exerted enhancing effects on their development, while
      dimethyl trisulfide also tended to increase them. To investigate possible
      mechanisms of the modifying influence, sequential changes in ornithine
      decarboxylase activity (ODC) over 24 h were measured in AM-treated liver tissue
      without prior DEN initiation. The activity started to increase by 4 h after AM
      treatment, and reached maximum at 16 h, compared to controls. Spermidine/spermine
      N1-acetyltransferase activity was not significantly changed. An increase in
      proliferating cell nuclear antigen-positive cells followed the elevation of ODC
      activity. These results suggest that IAIE, DPT, and AM promote rat
      hepatocarcinogenesis and their promoting effect might be caused by increased cell
      proliferation with increased polyamine biosynthesis. In evaluating relationships
      between diet and cancer, it is thus appropriate to consider not only a possible
      protective role of garlic and onions, but also enhancing effects.

PMID- 7829390
TI  - Enhancement of T cell receptor signaling of tumor-infiltrating lymphocytes by
      retrovirally mediated fyn gene transduction.
AB  - We conducted retrovirally mediated transduction of fyn gene into tumor
      infiltrating lymphocytes (TILs) in an attempt to augment T cell receptor-CD3
      complex signal transduction, using TILs obtained from six patients with
      epithelial ovarian cancer. The expression of the transduced gene was more than
      five times that of endogenous fyn gene. In all preparations, the cytolytic
      activity of the TILs against autologous tumor cells, but not allogeneic tumor
      cells, was significantly enhanced (P < 0.01) by transduction of fyn gene. In
      addition, when TILs were treated with anti-CD3 antibody to stimulate T cell
      receptor-CD3 complex, fyn-gene-transduced TILs showed about two times higher
      proliferation (P < 0.05) and secreted 2.2 to 11.7 times more tumor necrosis
      factor-beta (P < 0.05) than nontransduced TILs. These results could have
      important implications for TILs-mediated gene therapy for cancer.

PMID- 7829391
TI  - Epstein-Barr virus-associated post-transplant non-Hodgkin's lymphoma:
      establishment and characterization of a new cell line.
AB  - A new human lymphoma cell line derived from pulmonary non-Hodgkin's lymphoma that
      developed in a renal transplant recipient was established from the patient's
      pleural effusion and designated PTLC-1. PTLC-1 grew aggressively in suspension,
      forming very loose clumps with a doubling time of about 18.9 h. The
      morphological, chromosomal, and immunophenotypic characteristics of the patient's
      tumor cells and PTLC-1 cells were very similar. PTLC-1 showed a monoclonal
      rearrangement of IgH gene and was highly tumorigenic in athymic nude mice. In
      situ hybridization, Southern blot hybridization and polymerase chain reaction
      demonstrated the presence of Epstein-Barr virus (EBV) genome in the patient's
      tumor and PTLC-1. PTLC-1 has been maintained in culture for over 60 months. Since
      EBV has been implicated in the pathogenesis of post-transplant lymphoma, this new
      cell line should serve as a useful experimental model for studying the etiology
      and biology of lymphoma developing in organ transplant recipients.

PMID- 7829392
TI  - High frequency of p53 abnormality in laryngeal cancers of heavy smokers and its
      relation to human papillomavirus infection.
AB  - A series of 41 laryngeal squamous cell carcinomas was examined for p53
      abnormalities and human papillomavirus (HPV) infection by an immunohistochemical
      and/or molecular approach. Immunohistochemically, p53 over-expression was
      observed in about 60% of the cancers, of which 12 were revealed to contain point
      mutations of p53 by a combination of the single-strand conformational
      polymorphism technique and direct sequencing. The p53 point mutations ranged from
      codons 157 to 278 and most of these mutations lay in two "hot spots" (codon 157
      in four cancers and codon 248 in three cancers). The majority of p53 mutations,
      both transversions (seven cancers) and transitions (five cancers), occurred at
      the G nucleotide of the codons. An analysis of the clinical information indicated
      that p53 point mutation was frequently observed in heavy smokers with an average
      Brinkman index score of more than 1000. On the other hand, HPV DNA, type 16 or
      18, was detected in a quarter of the laryngeal cancers. Of eleven HPV-positive
      cases, nine were immunohistochemically positive for p53, of which four contained
      a p53 point mutation. These results suggested no inverse relation between p53
      mutation and HPV infection in laryngeal cancers. Our study indicates that p53
      abnormalities are related to smoking history and the correlation might be better
      for smoking and chemical mutagenesis than for HPV.

PMID- 7829393
TI  - Suppression of G1 arrest and enhancement of G2 arrest by inhibitors of poly(ADP
      ribose) polymerase: possible involvement of poly(ADP-ribosyl)ation in cell cycle
      arrest following gamma-irradiation.
AB  - Low-dose gamma-irradiation of mouse embryonic fibroblast C3D2F1 3T3-a cells
      caused G1 arrest along with G2 arrest and inhibition of replicative DNA
      synthesis. When the cells were cultured in the presence of inhibitors of poly(ADP
      ribose) polymerase [EC 2.4.2.30], such as 3-aminobenzamide, benzamide and
      luminol, G1 arrest of C3D2F1 3T3-a cells was suppressed and enhancement of G2
      arrest was observed. In contrast, 3-aminobenzoic acid, a non-inhibitory analog of
      3-aminobenzamide, did not suppress G1 arrest following gamma-irradiation. These
      results suggest that the poly(ADP-ribosyl)ation reaction is critical for the
      pathway of G1 arrest and is also involved in the pathway of G2 arrest.

PMID- 7829394
TI  - Isolation of genes differentially expressed between the Yoshida sarcoma and long
      survival Yoshida sarcoma variants: origin of Yoshida sarcoma revisited.
AB  - The Yoshida sarcoma (YS) is characterized by growth as "free cells" in ascites.
      Long-survival Yoshida sarcoma (LY) variants, which develop after transplantation
      of YS into immunologically conditioned Donryu rats, in contrast, form "islands"
      in ascites. A representational difference analysis (RDA) approach was adopted to
      isolate genes differentially expressed between YS and LY variants to elucidate
      the molecular mechanism of their development. Fifteen clones presenting
      differences in expression were characterized. Nine genes (those encoding for the
      high-affinity IgE receptor gamma chain, pJG116 repetitive sequence, non neuronal
      enolase, proteasome subunit RC1, cytotoxic T lymphocyte-associated gene
      transcript CTLA-1, interleukin-2 receptor gamma chain, and three unknown
      sequences) expressed mRNA in YS, but showed lower or no expression of mRNA in
      LYs. The mRNAs of the other six genes (those encoding for cytokeratin 8,
      cytokeratin18 (Endo B), TIMP2 and three unknown sequences) were not found in YS,
      but were present in LYs. Interestingly, CTLA-1 is a non-epithelial
      (hematopoietic) cell-specific gene in terms of transcription, while cytokeratin 8
      and cytokeratin 18 are both epithelium-specific genes. Immunohistochemically, YS
      expressed T-cell specific antigens CD2 and CD3, and T cell receptor beta and
      gamma chain genes were rearranged in YS, but not in LYs. Moreover, using
      restriction fragment length polymorphism probes, we found that LYs exhibited
      different cell lineage from YS. Thus, our present findings, unexpectedly, raise
      fundamental questions concerning the cellular origins of YS and LY variants
      rather than pointing to any specific mechanism to explain the LY phenomenon.

PMID- 7829395
TI  - Characteristics of human hepatocellular carcinoma cell lines (Hep-KANO) derived
      from a non-hepatitic, non-cirrhotic hepatitis B virus carrier.
AB  - We have established two cell lines of hepatocellular carcinoma [Hep-KANO, clone 1
      (CL-1) and clone 2 (CL-2)] from tissue obtained at autopsy of a hepatitis B virus
      (HBV) carrier without histological signs of hepatitis or liver cirrhosis. These
      cell lines differed considerably from each other in morphology, proliferation
      pattern, alpha-fetoprotein secretion, albumin synthesis, cytokine secretion,
      modal chromosome number and transplantability to nude mice. Histologic
      examinations also revealed differences between them. Amplification of N-myc, L
      myc, H-ras, K-ras, N-ras, c-erb-B and c-erb-B-2 and rearrangement of p53 were not
      found in either of the cell lines. However, CL-1 and CL-2 showed an identical HBV
      DNA integration pattern. A 4-fold amplification of c-myc was observed in CL-1,
      but not in CL-2. Hep-KANO cell lines, CL-1 and CL-2 may be useful in clarifying
      the question of whether hepatocarcinogenesis is directly caused by HBV infection.

PMID- 7829396
TI  - Facilitation of autonomous phenotype acquisition in androgen-dependent Shionogi
      carcinoma 115 cells by transfection of androgen-induced growth factor expression
      vector.
AB  - Androgen-induced growth factor (AIGF) is an autocrine growth factor for androgen
      dependent SC-3 cells, which is induced by androgen stimuli. To elucidate the
      mechanism of the progression from hormone-dependent to -independent tumor, we
      transfected an expression vector of cDNA encoding AIGF into SC-3 cells and
      established a stable transfectant (A1) expressing AIGF. A1 cells showed enhanced
      DNA synthesis. This enhanced DNA synthesis was blocked by exposing the cells to
      AIGF antisense oligonucleotides, heparin, or suramin, indicating that enforced
      AIGF expression is responsible for the increase in DNA synthesis. However, A1
      cells did not grow in serum-free medium unless stimulated with androgen.
      Recloning from A1 cells in semi-solid agar supplemented with fetal calf serum but
      without androgen quickly generated an autonomous subline that was able to grow
      rapidly in the serum-free medium irrespective of androgen stimulus. Mock
      transfected SC-3 cells failed to form any colony under identical conditions.
      These results suggest that stable expression of AIGF alone is not sufficient for,
      but facilitates the conversion of SC-3 cells from androgen-dependent to 
      independent phenotype.

PMID- 7829397
TI  - Characterization of mice bearing subclones of colon 26 adenocarcinoma
      disqualifies interleukin-6 as the sole inducer of cachexia.
AB  - A subclone (clone 20) of chemically induced, murine colon adenocarcinoma with a
      potent ability to induce cachexia and another subclone (clone 5) without such an
      activity were transplanted to syngeneic mice (CDF1) and their tissue weights,
      blood components and cytokine levels in sera were compared. Mice transplanted
      with clone 20 showed a profound body-weight loss by 15 days after inoculation
      when the tumor accounted for less than 1% of the body weight, along with marked
      reduction of food and water intakes. Thereafter, they transiently gained in body
      weight with restoration of food and water intakes. Thus, the change in body
      weight was biphasic and not proportional to the tumor size. Body fat was lost
      preferentially, accompanied with a decrease in plasma triglyceride levels. The
      thymus contracted remarkably, and the peripheral lymphocyte count decreased
      extensively. Mice transplanted with clone 5, in contrast, did not show any of
      these changes characteristic of cachexia. Serum concentration of interleukin-6,
      which has been proposed as the principal inducer of cachexia in mice with colon
      26, increased in mice with clone 5 to levels comparable to those in mice with
      clone 20. The changes in mice bearing clone 20 could not all be explained in
      terms of known biological activities of interleukin-6. Additional unknown
      factors, therefore, are presumed to contribute to cachexia in mice with clone 20.
      Identification of them should be helpful in the care of cachectic patients.

PMID- 7829398
TI  - Polypoid carcinoma of the esophagus.
AB  - Polypoid carcinoma of the esophagus is rare and little is known about its
      clinical and histopathologic features. We reviewed 500 surgical cases of
      esophageal carcinoma and analyzed 12 polypoid carcinomas. Clinical records were
      reviewed. Histologic examination was done on an average of 68 sections in each
      tumor. Immunohistochemical examination for proliferating cell nuclear antigen
      (PCNA) was done in selected sections. No special findings were seen with respect
      to age, sex, symptoms, or tumor location. The tumors, however, had several
      interesting features: 1) the main histologic type was squamous cell carcinoma,
      but other histologic features such as so-called carcinosarcoma, adenoid cystic
      carcinoma, and verrucous carcinoma were occasionally seen, 2) bidirectional
      differentiation to squamous and adenocarcinomatous components was recognized, 3)
      intraepithelial spreading of the carcinoma was often present, 4) depth of
      invasion in the wall was often shallow, and 5) the prognosis was relatively good.
      The PCNA labeling index was well correlated with lymphatic or blood vessel
      permeation.

PMID- 7829399
TI  - Improvement of macrophage dysfunction by administration of anti-transforming
      growth factor-beta antibody in EL4-bearing hosts.
AB  - An experimental therapy for improvement of macrophage dysfunction caused by
      transforming growth factor-beta (TGF-beta) was tried in EL4 tumor-bearing mice.
      TGF-beta was detected in cell-free ascitic fluid from EL4-bearers, but not in
      that from normal mice, by western blot analysis. The ascites also showed growth
      suppressive activity against Mv1Lu cells, and the suppressive activity was
      potentiated by transient acidification. To investigate whether the functions of
      peritoneal macrophages were suppressed in EL4-bearers, the abilities to produce
      nitric oxide and tumor necrosis factor-alpha (TNF-alpha) upon lipopolysaccharide
      (LPS) stimulation were measured. Both abilities of macrophages in EL4-bearing
      mice were suppressed remarkably on day 9, and decreased further by day 14,
      compared with non-tumor-bearing controls. TGF-beta activity was abrogated by
      administration of anti-TGF-beta antibody to EL4-bearing mice. While a large
      amount of TGF-beta was detected in ascitic fluid from control EL4-bearers, little
      TGF-beta was detectable in ascites from EL4-bearers given anti-TGF-beta antibody.
      Furthermore, while control macrophages exhibited little or no production of
      nitric oxide and TNF-alpha on LPS stimulation in vitro, macrophages from EL4
      bearers administered with anti-TGF-beta antibody showed the same ability as
      normal macrophages. These results clearly indicate that TGF-beta contributes to
      macrophage dysfunction and that the administration of specific antibody for TGF
      beta reverses macrophage dysfunction in EL4-bearing hosts.

PMID- 7829400
TI  - Inhibitory effect of oversulfated fucoidan on invasion through reconstituted
      basement membrane by murine Lewis lung carcinoma.
AB  - We investigated the effects of native, oversulfated, and desulfated fucoidans and
      heparin on the invasion of 3 LL cells through Matrigel. Of the four
      polysaccharides tested, oversulfated fucoidan was the most potent inhibitor of
      tumor cell invasion and inhibited most potently and specifically the tumor cell
      adhesion to laminin. Sodium dodecyl sulfate-polyacrylamide gel electrophoretic
      analysis of the binding of elastase-cleaved laminin to fucoidan- and heparin
      Sepharoses showed that both polysaccharides bound to the 62 and 56 kDa fragments.
      Pretreatment of 3LL cells with native or oversulfated fucoidan reduced their
      adhesive potency to laminin. The two fucoidans inhibited further the laminin
      binding of 3 LL cells which had been pretreated with a laminin-based
      pentapeptide, YIGSR. These results suggest that fucoidan specifically binds to
      not only the heparin binding domain(s) of laminin but also site(s) other than the
      cell surface laminin receptor. 3 LL cells secreted a 50 kDa form of urokinase
      type plasminogen activator (u-PA). The extracellular level of u-PA activity was
      increased 1.7 times by addition of laminin but not type IV collagen. Oversulfated
      fucoidan most potently reduced the increased u-PA levels. Therefore, the
      reduction in in vitro invasiveness of 3 LL cells in response to either fucoidan
      or its oversulfated derivative may result from an inhibition of physical
      interaction between the tumor cells and the Matrigel (laminin), followed by a
      suppression of the laminin-induced increase in extracellular u-PA.

PMID- 7829401
TI  - A randomized cross-over study of high-dose metoclopramide plus dexamethasone
      versus granisetron plus dexamethasone in patients receiving chemotherapy with
      high-dose cisplatin.
AB  - We carried out a randomized, single-blind, cross-over trial to compare the
      antiemetic effect, for both acute and delayed emesis, of granisetron plus
      dexamethasone (GRN+Dx) with that of high-dose metoclopramide plus dexamethasone
      (HDMP+Dx). Fifty-four patients with primary or metastatic lung cancer, given
      single-dose cisplatin (> 80 mg/m2) chemotherapy more than twice, were enrolled in
      this study. They were treated with both HDMP+Dx and GRN+Dx in two consecutive
      chemotherapy courses. On day 1, patients experienced a mean of 2.5 (SD = 4.3) and
      0.1 (SD = 0.4) episodes of vomiting in the HDMP+Dx and the GRN+Dx groups,
      respectively (P = 0.0008). Complete response rate on day 1 was 45 and 90% in the
      HDMP+Dx and the GRN+Dx groups, respectively (P = 0.0001). Patients treated with
      GRN+Dx had a tendency to suffer more episodes of vomiting than the HDMP+Dx group
      on days 2-5, but it was not statistically significant. Twenty-four patients (57%)
      preferred the GRN+Dx treatment and 14 patients (33%), HDMP+Dx. In the HDMP+Dx
      group, nine patients (21%) had an extrapyramidal reaction, and 5 patients (12%)
      had constipation that lasted for at least two days. In contrast, no patients had
      extrapyramidal reactions, and 18 patients (43%) had constipation in the GRN+Dx
      group (P < 0.01). GRN+Dx was more effective than HDMP+Dx only in preventing the
      acute emesis induced by cisplatin. An effective treatment for delayed emesis is
      still needed.

PMID- 7829403
TI  - Photodynamic therapy using a diode laser with mono-L-aspartyl chlorin e6 for
      implanted fibrosarcoma in mice.
AB  - We have developed a new high-power red (664 nm) laser diode system for
      photodynamic therapy (PDT) with mono-L-aspartyl chlorin e6 (NPe6). Meth-A
      fibrosarcoma cells (1 x 10(6)) were implanted subcutaneously in the right hind
      leg of 4-week-old BALB/c female mice. One week later, diode laser irradiation was
      applied 5 h after the intravenous administration of NPe6 to each tumor-bearing
      mouse. In the first study, the time course of intratumor temperature increase
      during PDT was measured by using a 23-guage thermocouple hypodermic needle at a
      depth of 2 mm from the tumor surface. In the second study, 6 groups of 10 to 17
      tumor-bearing mice were treated with the diode laser 5 h after intravenous
      administration of NPe6 at the dose of 1.25, 2.5, 5.0 or 7.5 mg/kg i.v. per mouse.
      Total photoirradiation ranged from 0 to 150 J/cm2 and the dose rate was adjusted
      to 100 mW/cm2. Percentages of cures were determined from numbers of mice
      apparently disease-free 50 days after treatment. The results showed that this
      diode laser is effective in PDT of implanted fibrosarcoma after NPe6
      administration. It also confirmed that the therapeutic effects of PDT were not
      due to hyperthermia. Moreover, the diode laser beam was demonstrated by CCD
      technology to be uniform in intensity throughout the photoirradiated field.

PMID- 7829402
TI  - Potentiation of cis-diammine(1,1-cyclobutanedicarboxylato)platinum(II) by
      amphotericin B in BALB/c nude mice bearing human ovarian carcinoma cells.
AB  - Human ovarian carcinoma cells (HRA) were sensitized to cis-diammine(1,1
      cyclobutanedicarboxylato)platinum(II) (CBDCA) 1.2-, 2.1- and 3.4-fold by
      treatment with amphotericin B (AMB) at concentrations of 2.1, 5.4, and 10.8
      microM, respectively. Moreover, the intracellular accumulation of platinum after
      2-h exposure to CBDCA was increased significantly by AMB treatment. For
      estimating the enhancing effect of AMB on CBDCA cytotoxicity in vivo, we prepared
      HRA cell-inoculated nude mice. Ascites was evident 7 to 9 days after
      intraperitoneal (i.p.) inoculation of HRA cells, and the mice died of
      intraabdominal carcinomatosis 11 to 14 days (mean survival time (MST): 12.0 +/-
      1.0 days) after inoculation. Treatment with AMB (2.0 mg/kg) alone increased the
      MST by only 1.2 days. Simultaneous treatment with CBDCA (12 or 15 mg/kg) and AMB
      (0.5 to 2.0 mg/kg) produced a significant increase in MST compared to treatment
      with CBDCA alone. Maximal MST (38.5 days) was obtained by treatment with 15 mg/kg
      CBDCA plus 2.0 mg/kg AMB, whereas the MST with 15 mg/kg CBDCA alone was 15.8
      days. A drug accumulation study demonstrated that platinum accumulation in tumor
      tissues after i.p. treatment with CBDCA and AMB in tumor-bearing nude mice was
      increased significantly compared to treatment with CBDCA alone. These findings
      indicate that intraperitoneal combination chemotherapy with CBDCA and AMB is
      useful in nude mice with advanced ovarian carcinoma.

PMID- 7829404
TI  - Comparative DNA analysis by image cytometry and flow cytometry in non-small cell
      lung cancer.
AB  - To determine whether image cytometry (ICM) is advantageous for clinical DNA
      analyses of tumor cells, nuclear DNA contents measured by ICM were compared with
      those by flow cytometry (FCM), using 46 samples of non-small cell lung cancers.
      ICM was performed on smear specimens of fresh materials (f-ICM) and cell
      suspensions obtained from paraffin-embedded tumors (p-ICM). The same cell
      suspensions were also analyzed by FCM (p-FCM). Aneuploid rates/coefficient of
      variation (CV) of f-ICM, p-ICM, and p-FCM were 76.1/4.90, 71.7/5.01 and
      60.9/5.31%, respectively. There was a high correlation in the DNA indices between
      p-ICM and p-FCM (r = 0.80). In the comparative DNA analysis, there were seven
      discordant samples. Six of them were estimated as aneuploid by p-ICM, but they
      were miscounted as diploid or undefinable (impossible) by p-FCM. This was caused
      by measuring condensed nuclei or debris. All "impossible" samples in p-FCM were
      squamous cell carcinoma with necrosis. In cell cycle analysis, the S and S+G2/M
      phase fractions in diploid samples were higher in p-ICM than those in p-FCM (P <
      0.005), because the G0/G1 phase (2N) fraction presented by FCM was composed of
      cancer and non-malignant cells in diploid cancers. In ICM, they can be separately
      measured by means of morphological selection. These findings indicated that ICM
      is superior to FCM, especially for the practical DNA measurement of a few cancer
      cells and in the evaluation of the proliferation rates.

PMID- 7829405
TI  - Successors to acyclovir.

PMID- 7829406
TI  - Molecular genetics of drug resistance in Mycobacterium tuberculosis.
AB  - Tuberculosis (TB) is the single largest killer among infectious diseases. The
      recent resurgence of TB together with outbreaks of multidrug resistant
      tuberculosis has focused attention on understanding the mechanisms of such drug
      resistance. Because of the relative neglect of TB research in the past and late
      arrival of mycobacterial genetic tools, the molecular mechanisms of drug
      resistance in TB remained largely unknown until very recently. In this paper we
      review recent progress on the mechanisms of resistance to three major anti-TB
      drugs; isoniazid, rifampicin and streptomycin. While the resistance mechanisms
      for rifampicin and streptomycin are similar to those found in other bacteria,
      isoniazid susceptibility and resistance is unique to Mycobacterium tuberculosis.
      So far, mutations in two chromosomal loci, katG and inhA have been found to be
      involved in isoniazid resistance in TB. Identification and characterization of
      mutations responsible for resistance opens up new possibilities for rapid
      detection of drug resistant strains. Molecular understanding of drug resistance
      and drug action in M. tuberculosis may eventually lead to rational design of new
      anti-TB drugs.

PMID- 7829407
TI  - Disruption of the transmembrane pH gradient--a possible mechanism for the
      antibacterial action of azelaic acid in Propionibacterium acnes and
      Staphylococcus epidermidis.
AB  - The effect of the topical acne treatment azelaic acid on the transmembrane proton
      gradient (delta pH) of Propionibacterium acnes and Staphylococcus epidermidis was
      studied in vitro at external pH values found on human skin (pH 4.0-6.0). Bacteria
      were grown in defined media using continuous culture and delta pH was estimated
      by measuring the accumulation of [14C] benzoic by the cells using flow dialysis.
      In both P. acnes and S. epidermidis the addition of 30 mM azelaic acid and the
      membrane active inhibitors nigericin (150 microM) and CCCP (150 microM) resulted
      in a rapid release of [14C] label into the dialysate indicating the dissipation
      of delta pH between external pH values of 4.0-6.0. The addition of 60 mM NaCl as
      an iso-osmotic control and 150 microM valinomycin did not induce the release of
      [14C] label. The addition of 30 mM azelaic acid reduced the delta pH of P. acnes
      by 44% at external pH 4.0 and 28% at external pH 6.0. In S. epidermidis 30 mM
      azelaic acid reduced delta pH by 88% at external pH 5.0 and 20% at external pH
      6.0. Rapid loss of viability occurred in suspensions of P. acnes and S.
      epidermidis containing 30 mM azelaic acid at pH 4.0 with no viable cells
      recovered after 60 min incubation. At pH 6.0 little change in viable numbers of
      P. acnes and S. epidermidis were observed over a 2 h incubation period. The
      results indicate that the antibacterial activity of azelaic acid is associated
      with the perturbation of intracellular pH.

PMID- 7829408
TI  - In-vitro effects of antimicrobial agents on Pseudomonas aeruginosa biofilm
      formation.
AB  - The in-vitro effects of ten antimicrobial agents on the biofilm formation of
      Pseudomonas aeruginosa were investigated. The production of alginic acid by
      mucoid P. aeruginosa cells cultured in agar media with sub-MICs of antimicrobial
      agents was quantified by high-performance liquid chromatography. Alginic acid
      production was inhibited by 1/4 MIC of minocycline (P < 0.002) and tobramycin (P
      < 0.02), and by 1/256-1/1/64 MIC of macrolides (erythromycin, clarithromycin,
      roxithromycin, and rokitamycin) and clindamycin (P < 0.02), compared with drug
      free controls. Piperacillin, ceftazidime, and ofloxacin did not inhibit alginic
      acid production. The production of exopolysaccharide by non-mucoid P. aeruginosa
      cells grown on silicone plates in sub-MICs of antimicrobial agents was determined
      by quantitative tryptophan assay. Exopolysaccharide production was inhibited by
      1/16 MIC of macrolides and clindamycin, but not by other antimicrobial agents.
      Electron microscopy showed that biofilm formation by mucoid and non-mucoid type
      P. aeruginosa strains was inhibited by sub-MICs of erythromycin and correlated
      with the in-vitro production of alginic acid and exopolysaccharide. These results
      suggest that sub-MICs of macrolides and clindamycin suppress biofilm formation by
      P. aeruginosa and that intractable chronic respiratory tract infections due to P.
      aeruginosa might be prevented.

PMID- 7829409
TI  - In-vitro activity of quinolones and macrolides against mycobacteria.
AB  - The activities of eight quinolones (ciprofloxacin, clinafloxacin, levofloxacin,
      ofloxacin, A-80556, sparfloxacin, temafloxacin and tosufloxacin) and three
      macrolides (azithromycin, clarithromycin and erythromycin) against 98 clinical
      isolates of Mycobacterium tuberculosis and 120 isolates of five different
      atypical mycobacterial species including 20 Mycobacterium kansasii, 25
      Mycobacterium scrofulaceum, 25 Mycobacterium avium/intracellulare, 25
      Mycobacterium chelonae and 25 Mycobacterium fortuitum were determined with the
      Middlebrook 7H9 broth macrodilution method. Sparfloxacin, clinafloxacin,
      levofloxacin, ciprofloxacin and ofloxacin were active against M. tuberculosis
      (MIC90 0.06-0.5 mg/L; MBC90 0.125-2.0 mg/L). However, higher MIC90S and MBC90S of
      these quinolones were obtained for strains of multi-drug resistant M.
      tuberculosis. The macrolides tested had poor activity against M. tuberculosis
      isolates (MIC90 > 8.0 mg/L). Furthermore, high MIC90S of the quinolones and
      macrolides (2.0 to 8.0 mg/L) were obtained for clinical isolates of atypical
      mycobacteria, with the exception of clarithromycin against M. kansasii (MIC90 =
      1.0 mg/L) and sparfloxacin against M. scrofulaceum (MIC90 = 1.0 mg/L).

PMID- 7829410
TI  - The accumulation of fluoroquinolones in Staphylococcus aureus during the
      postantibiotic effect.
AB  - The accumulation of radiolabelled pefloxacin, norfloxacin, and lomefloxacin was
      determined in Staphylococcus aureus during log phase growth, the postantibiotic
      effect (PAE), and at 1, 4 and 6 h post PAE. Uptake in actively growing cells was
      consistent with a non-saturable passive diffusion process. The addition of
      metabolic inhibitors significantly increased accumulation consistent with the
      presence of an energy dependent efflux system. Accumulation of all three
      fluoroquinolones in PAE phase cells was significantly increased compared to that
      which occurred in actively growing cells. In contrast to cells in the log phase,
      addition of metabolic inhibitors to PAE phase cells did not result in a
      significant increase in drug accumulation. Uptake kinetics 1 h and 4 h post PAE
      were similar to those found during the PAE phase. Organisms required 6 h after
      the end of the PAE phase before normal uptake kinetics of fluoroquinolones
      resumed.

PMID- 7829411
TI  - Azithromycin uptake and intracellular accumulation by Toxoplasma gondii-infected
      macrophages.
AB  - The uptake of azithromycin and erythromycin was measured in RAW 264.7 mouse
      macrophages infected with Toxoplasma gondii to determine whether the activity of
      macrolides could be correlated with their degree of host cell penetration. Uptake
      was expressed as the ratio of the intracellular (I) to the extracellular (E)
      concentrations. After infection, the intracellular accumulation of macrolides was
      equivalent to that measured in uninfected cells and azithromycin reached an I/E
      ratio of 105.8 +/- 8.0 in infected macrophages incubated with 20 mg/L of drug.
      The release of azithromycin from macrophages previously exposed to the drug was
      enhanced by exposure to Micrococcus luteus and phorbol myristate acetate but not
      after infection with T. gondii. Azithromycin accumulates readily and remains
      inside T. gondii-infected macrophages thereby interfering with the growth of the
      parasite which was confirmed by growth-inhibition experiments and by electron
      microscopy.

PMID- 7829412
TI  - Effect of newer quinolones on the extra- and intra-cellular chemiluminescence
      response of human polymorphonuclear leucocytes.
AB  - The direct effect of four quinolones on the intracellular production and
      extracellular release of reactive oxygen species was investigated in vitro using
      a chemiluminescence (CL) assay. Polymorphonuclear leucocytes (PMNs) were obtained
      from healthy volunteers and exposed for 10 min at 37 degrees C to 1.6, 6.25 and
      25 mg/L ofloxacin, ciprofloxacin, sparfloxacin and temafloxacin. The luminol
      dependent CL response of the PMNs was then measured for 30 min following
      stimulation with nonopsonized zymosan or phorbol myristate acetate (PMA). The
      intracellular CL response was also measured for 30 min during phagocytosis of
      lumispheres. The integrated CL was calculated and compared for cells which were
      incubated with the antibiotic and unincubated controls. Preincubation with
      ofloxacin resulted in increased zymosan and PMA-induced, luminol-dependent CL.
      Similar increases were observed for ciprofloxacin except that 25 mg/L decreased
      the PMA-induced, luminol dependent CL. Preexposure to ofloxacin and ciprofloxacin
      did not affect lumisphere-induced CL significantly, although there was a tendency
      for this to decrease after exposure to ciprofloxacin. In contrast sparfloxacin
      and temafloxacin caused progressive decreases in zymosan and PMA-induced, luminol
      dependent PMN CL which reached statistical significance at the higher
      concentrations. The same pattern was observed in the experiments using
      lumispheres. These findings indicate that these quinolones modulate the oxygen
      metabolism of PMNs and that this effect varies with the individual drug.

PMID- 7829413
TI  - Comparison of cefoperazone plus sulbactam with clindamycin plus gentamicin as
      treatment for intra-abdominal infections.
AB  - This study compared the safety and efficacy of cefoperazone plus sulbactam with
      that of clindamycin plus gentamicin in the treatment of intra-abdominal
      infection. Seventy-six patients were included in the analysis of an open,
      randomized, comparative, single-site trial. Forty-seven patients received
      cefoperazone-sulbactam, and 29 patients received clindamycin plus gentamicin.
      Thirty-three patients (70%) who received cefoperazone-sulbactam and 15 patients
      (52%) who received clindamycin plus gentamicin were cured of infection, did not
      suffer a relapse within one month after the end of treatment, and did not receive
      any other antibiotics during the follow-up period (P = 0.17). In patients treated
      with cefoperazone-sulbactam there were four cases of superinfection, one patient
      had a prolonged prothrombin time, six patients had a poor response, two patients
      received antibiotics during follow-up, and one patient died during follow-up
      because of cancer. Treatment with clindamycin plus gentamicin was associated with
      five cases of superinfection, four patients had a poor response, four patients
      had a drug reaction, and one patient required antibiotics in the follow-up
      period. Serum levels of cefoperazone-sulbactam measured at one and three hours
      after dosing were consistent with earlier findings in normal volunteers. Two
      hundred and one pathogens were isolated, and 17 of 122 aerobic isolates (14%)
      were resistant to cefoperazone-sulbactam, and 17 of 122 (14%) were resistant to
      both clindamycin and gentamicin. Eleven of 79 (14%) anaerobic isolates were
      resistant to cefoperazone, none was resistant to cefoperazone-sulbactam, and 10
      of 79 (13%) were resistant to clindamycin. The results of this study show that
      cefoperazone-sulbactam is an effective and safe alternative to clindamycin plus
      gentamicin in the treatment of intra-abdominal infections.

PMID- 7829414
TI  - In-vitro activity of OPC-17116 against bacterial enteric pathogens.

PMID- 7829415
TI  - The susceptibility of Helicobacter pylori to 12 antimicrobial agents, omeprazole
      and bismuth salts.

PMID- 7829416
TI  - The sensitivity of clinical isolates of anaerobic species to piperacillin
      tazobactam and other antimicrobial agents.

PMID- 7829417
TI  - Bacteriostatic and bactericidal activities of paromomycin against Mycobacterium
      avium complex isolates.
AB  - The MICs and MBCs of paromomycin for 32 Mycobacterium avium complex (MAC) strains
      isolated from patients with the acquired immunodeficiency syndrome were
      determined by a radiometric broth dilution method. The MICs for the majority of
      strains were either 8 or 16 mg/L and the MBCs were four- to eight-fold higher.
      Paromomycin merits further evaluation as oral prophylaxis against disseminated
      MAC infection.

PMID- 7829418
TI  - Assay of serum teicoplanin concentrations in clinical specimens: a comparison of
      isocratic high performance liquid chromatography with polarisation
      fluoroimmunoassay and bioassay.

PMID- 7829419
TI  - Antibiotic policies in Dutch hospitals for the treatment of pneumonia.
AB  - The guidelines used in Dutch hospitals for the treatment of pneumonia as
      described in antibiotic formularies are described. A total of 42 formularies were
      examined. Amoxycillin was the most frequently used agent in the treatment of
      community-acquired pneumonia and a wide variety of drugs was used for the
      treatment of nosocomial pneumonia, of which cefuroxime, alone or in combination
      with an aminoglycoside, was used most often. Benzylpenicillin was the most
      frequently used drug in community-acquired aspiration pneumonia; this drug, in
      combination with an aminoglycoside, was also the drug of choice in hospital
      acquired aspiration pneumonia. Treatment of pneumonias with known or presumed
      pathogens was also surveyed and the most usual drugs of choice were
      benzylpenicillin for pneumococci, flucloxacillin for staphylococci, amoxycillin
      for Haemophilus influenzae, cefuroxime for Enterobacteriaceae (cefuroxime),
      cotrimoxazole for Pneumocystis carinii, doxycycline and erythromycin for
      Mycoplasma pneumoniae and erythromycin for Legionella pneumophila. Relatively
      wide variations in dosage guidelines were observed for benzylpenicillin and
      amoxycillin. Only a few formularies gave guidelines for the duration of
      treatment.

PMID- 7829420
TI  - A clarithromycin sensitivity survey.

PMID- 7829421
TI  - A clarithromycin sensitivity survey.

PMID- 7829422
TI  - Rapid HPLC assay of clinafloxacin, fleroxacin, levofloxacin, sparfloxacin and
      tosufloxacin.

PMID- 7829423
TI  - Itraconazole concentrations during continuous haemodiafiltration.

PMID- 7829424
TI  - Tissue concentrations of an orally administered antibiotic in diabetic patients
      with foot infections.

PMID- 7829425
TI  - Lack of toxicity of long-term, high total dose liposomal amphotericin B.

PMID- 7829426
TI  - Patterns of food choices among Arkansans with less than a high school education.
AB  - This study surveyed students in Adult Basic Education (ABE) Programs in Arkansas
      to determine their pattern of food choices. The results indicated that entire
      food groups, e.g. vegetables, fruits, or milk were not included in the diets of
      many participants. This population more frequently chose high fat than low fat
      foods. Regression analyses indicated that the choice of low fat products
      increased with age and family income level. The most dramatic trends were in
      changes in consumption of dairy products, fruits, and vegetables. These data
      support the need for nutrition education in Arkansans with less than a high
      school education.

PMID- 7829427
TI  - Epilepsy and pregnancy: mother and child.
AB  - Pregnancy in women that have epilepsy is not contraindicated. Definite associated
      risks do exist but are not as great as once believed. The woman of child bearing
      age with epilepsy should be educated and informed about the risk of increased
      seizures and the complications associated with the pregnancy and AED's. Seizure
      frequency may increase in one-third to one-half of women during pregnancy. AED
      serum levels decrease during pregnancy and may have a negative impact on seizure
      control. The risks for mother and child produced by generalized convulsions and
      especially status epilepticus far outweigh the potential risks associated with
      AED's. Prenatal obstetrical and neurological care during pregnancies of women
      with epilepsy is mandatory and can result in an improved outcome. All AED's do
      have some teratogenic potential, but this is much less than previously described.
      An understanding of the risks associated with epilepsy and pregnancy and
      appropriate therapy will result in a better outcome for both mother and child.

PMID- 7829428
TI  - Atrial myxoma.

PMID- 7829429
TI  - Radiological case of the month. Free intraperitoneal air.

PMID- 7829430
TI  - Tropical medicine as a speciality in India.

PMID- 7829431
TI  - Renal transplantation in HBsAg positive recipients.

PMID- 7829432
TI  - A study of hepatitis B surface antigen positive patients on haemodialysis and
      following transplantation.
AB  - Of 1339 patients who entered the dialysis and transplantation program, 104
      (7.77%) patients were HBsAg positive. On dialysis, 15 of 104 patients (14.42%)
      developed icteric hepatitis (serum bilirubin > 2 mg/d1) and 7 patients (6.73%)
      developed anicteric hepatitis (SGOT > twice the upper limit of normal--normal 5
      40 IU); one patient died of hepatic failure. Sixty five patients underwent live
      related transplantation. Actuarial graft survival at the end of 1 year, 2 years
      and 6 years were 81.67%, 73.98% and 69.36% respectively, and there was no
      significant difference compared to the negative group. 8 grafts (12.31%) were
      lost due to patient death due to infection in the HBsAg positive group compared
      to 27 out of 390 (6.923%) HBsAg negative patients (x2 = 1.88 P > 0.1). Post
      transplantation hepatic dysfunction was seen in 7 out of 65 (10.77%) patients and
      two patients died of hepatic failure.

PMID- 7829433
TI  - Plasma and urine osmolality in untreated thyroprivic hypothyroidism: effect of
      eltroxin therapy.
AB  - Plasma and urine osmolality were determined in 56 thyroprivic hypothyroid
      patients before and at 2 and 6 months of eltroxin treatment. Normal range of
      plasma osmolality (Posm) was defined at 95% confidence limits of values obtained
      from 25 euthyroid healthy controls. Thirty patients (53%) had lower Posm. The
      mean Posm in 56 hypothyroid patients increased from 283.4 +/- 2.06 SEM
      pretreatment, to 295.3 +/- 1.5 at 2 months (p < 0.001) and 296.5 +/- 1.07 at 6
      months. The improvements in Posm from those with lower values (30 patients) were
      more appreciable: 272.3 +/- 1.03 pretreatment, 290.3 +/- 1.9 at 2 months (p <
      0.001) and, 296.16 +/- 1.1 at 6 months (p < 0.001). Urine osmolality also
      increased from a low normal mean of 477.04 +/- 29.64 to 582.48 +/- 28.67 at 2
      months (P < 0.05) and 651.46 +/- 28.35 at 6 months (P < 0.001) of eltroxin
      treatment. Plasma and urine osmolality correlated positively with the clinical
      severity of hypothyroid state (plasma T3,T4,&TSH) (P < 0.001). These observations
      suggested a positive influence of thyroid hormones on plasma and urine osmolality
      and that plasma and urine osmolality increased with achievement of euthyroid
      state.

PMID- 7829434
TI  - Cytologic evaluation of nipple discharge in relation to mammary neoplasia.
AB  - Spontaneous nipple discharge as a presenting symptom was seen in 80 patients out
      of 3500 patients referred for cytologic examination of breast during last 5
      years. Gross appearance of nipple discharge was bloody (33), serous (29), milky
      (16) and yellowish (2). Cytology smears showed 5 cases of carcinoma and 14 cases
      of intraductal papilloma. One out of two cases of male nipple discharge revealed
      malignant cells. Bloody nipple discharge was more often associated with carcinoma
      and intraductal papilloma. Hence it underscored the importance of cytologic
      evaluation of bloody nipple discharge.

PMID- 7829435
TI  - Efficacy of magnesium sulphate in aluminium phosphide poisoning--comparison of
      two different dose schedules.
AB  - The results of an open randomised study on the efficacy of magnesium sulphate
      therapy in aluminium phosphide poisoning are presented. One hundred and fifty
      five patients divided in three groups and matched for age, sex, dose, duration
      and severity of poisoning constituted the subject matter. Significant
      hypomagnesemia was observed in patients who did not receive magnesium sulphate
      (group 1). Two dose schedules of MgSO4 therapy were tried. The dose schedule No.1
      given to patients of group 2 did not raise the magnesium levels significantly as
      compared to controls (group 4). The difference in the mortality between groups 1
      & 2 was also not significant. On the other hand, the dose schedule No.2 given to
      patients of group 3 raised the magnesium levels significantly and these remained
      above normal limits throughout the observed period. This dose schedule brought
      down the mortality significantly than dose schedule No.1 (p < 0.001). It was also
      found that dose schedule No.2 has been effective in reducing the mortality
      irrespective of dose of pesticide consumed and its efficacy was due to rapid rise
      in magnesium levels. It is suggested that hypomagnesemia might be responsible for
      high mortality of patients of aluminium phosphide poisoning and its correction
      has beneficial effect on the management and ultimate favourable outcome of the
      illness.

PMID- 7829436
TI  - Experience on loading dose--quinine therapy in cerebral malaria.
AB  - Twelve cases of cerebral malaria due to plasmodium falciparum, treated with
      loading dose of quinine (20 mg/kg salt in 500 ml of 5% glucose infused IV in 4
      hrs) are compared with eleven age and sex matched cases treated with conventional
      dose of 10 mg/kg. The parasite clearance rate was significantly faster in loading
      dose group. There was no difference in recovery time: the interval between the
      initiation of treatment to full recovery of consciousness in both groups. One
      patient had pretreatment hypoglycaemia and two cases in the conventional dose
      group developed hypoglycaemia during therapy. One patient died in conventional
      dose group due to multi-organ failure. Two litres blood exchange transfusion was
      also tried for this case. Mild cinchonism occurred in two cases after loading
      dose while this was observed only in one case in conventional dose group. There
      was no significant hypotension or ECG changes in any patient. Loading dose of
      quinine seems to be well tolerated and may clear parasitaemia faster in case of
      malaria due to Plasmodium falciparum (PF).

PMID- 7829437
TI  - Proteinuria in essential hypertension.
AB  - Porteinuria was quantitatively measured in twenty-five controls and eighty-one
      newly detected patients of essential hypertension without renal insufficiency.
      Hypertension was treated with enalapril, enalapril and nifedepine and nifedepine
      alone. Mean proteinuria was more in patients of hypertension as compared to
      controls (P < .001). Proteinuria decreased significantly (P < .001) after six
      weeks of control of hypertension. Patients treated with enalapril alone had
      maximum reduction in proteinuria than those with enalapril and nifedepine, and
      nifedepine alone.

PMID- 7829438
TI  - Renal dysfunction in patients of kala azar treated with sodium antimony
      gluconate.
AB  - We studied 27 patients presenting with renal dysfunction after Stibamate therapy.
      Eighteen patients were proved cases of Kala Azar, others of PUO. Out of 10 cases
      in whom Kidney biopsy was done, 6 had tubular necrosis, one had mild mesangial
      proliferation and 3 had normal picture.

PMID- 7829439
TI  - Diabetes and atherosclerosis as immune-inflammatory disorders: options for
      reversal of disease processes.
AB  - Hypothesis is presented to suggest that the present epidemic of DM and ACVD in
      Asian indians and possibly in other communities is iatrogenic resulting from what
      may be called modern malnutrition due to increased intake of total and n-6 fats
      and decreased intake of n-3 fat and antioxidants. Such a diet induces oxidative
      stress and activates the immune system. Imbalance between n-6 and n-3 fats result
      in inappropriate immune response. It also leads to increased and unbalanced
      biosynthesis of metabolites of n-6 fats. These are immune suppressive,
      proinflammatory and thrombogenic. They also contribute to insulin resistance and
      dyslipidemias. This makes DM and atherosclerosis as malnutrition related
      oxidative immune inflammatory disorders. Various risk factors are also the result
      of the same inappropriate response. Our intervention studies give considerable
      support to this hypothesis. It is suggested that simple correction of diet
      defects can reverse the disease process and thereby offer a simple, practical
      therapeutic option not only for the primary prevention of each of these disorders
      or their complications but also for the so called risk factors for these
      diseases. It is suggested that the real remedy for DM, ACVD and all the risk
      factors lies not in drugs or surgery but in the kitchen. However more studies are
      needed to precisely define various molecular mechanisms involved or the exact
      requirements of various nutrients.

PMID- 7829440
TI  - Drugs and the respiratory system.

PMID- 7829441
TI  - Brain transplant.

PMID- 7829442
TI  - Post-myocardial infarction risk stratification by exercise testing.

PMID- 7829443
TI  - Unusual clinical manifestations of cysticercosis.

PMID- 7829444
TI  - Congenital nephrotic syndrome of Finnish type with glomerular crescents.

PMID- 7829445
TI  - Disappearing ring lesion in CT scan in sensory epilepsy.

PMID- 7829446
TI  - Pemphigus vulgaris with cryoglobulinemia and cold agglutinin disease.

PMID- 7829447
TI  - Mitral valve annular calcification.

PMID- 7829448
TI  - Immunization against typhoid: a short review.

PMID- 7829449
TI  - Halofantrine in acute malaria.

PMID- 7829450
TI  - Halofantrine in acute malaria.

PMID- 7829451
TI  - Zinc in rheumatic heart valves.

PMID- 7829452
TI  - An atypical case of typhus fever with toxaemia from eastern zone of Assam.

PMID- 7829453
TI  - Acute viral cholecystitis in viral hepatitis.

PMID- 7829454
TI  - Pancytopenia: manifestation of enteric fever.

PMID- 7829455
TI  - INH-induced neurotoxicity.

PMID- 7829456
TI  - Tracheal schwannoma.

PMID- 7829457
TI  - Rabies presenting with priapism.

PMID- 7829458
TI  - Coronary MR angiography: a review.
AB  - With the advent of faster magnetic resonance imaging techniques, magnetic
      resonance angiography (MRA) of the coronary vessels has become a reality.
      Coronary MRA is a non-invasive imaging technique and preliminary clinical studies
      appear very promising. Coronary MRA can detect from 63% to 90% of all
      hemodynamically significant (= 50%) coronary lesions. Typically one can visualize
      the proximal 5.5 cm of the right coronary artery (RCA), the left main (LM)
      coronary artery, the proximal 4.5 cm of the left anterior descending (LAD)
      coronary artery and approximately 1.5 cm of the left circumflex (LCx) coronary
      artery. The current limitations of coronary MRA include: the inability to
      visualize the more distal portion of the coronary arteries and coronary artery
      branches, the need for consistent breath-holding and the need for special patient
      positioning. Coronary MRA techniques are improving and we feel will become an
      integral part for the evaluation of patients with ischemic heart disease.

PMID- 7829459
TI  - [Diagnosis of acute colonic diverticulitis: comparison with echography and
      tomodensitometry].
AB  - The sensitivity of ultrasonography (US) as the initial imaging procedure in acute
      diverticulitis of the left colon was retrospectively compared with that of
      computed tomography (CT) in 34 patients. Final diagnosis was based on clinical
      findings and follow-up in a first group of 20 patients with mild diverticulitis,
      and was proved by surgery in a second group of 14 patients with severe
      diverticulitis. In the first group, US showed findings consistent with
      diverticulitis in 19 patients, as did CT. The image of an inflamed diverticulum
      was shown by US in 10 patients. In the surgical group, findings consistent with
      diverticulitis were shown by US in 11 cases, and by CT in 13 cases. An inflamed
      diverticulum was not detected at US in this group of patients, presumably because
      the diverticulum was incorporated in the inflammatory process. These results
      suggest that US is a valuable technique in the initial evaluation of patients
      suspected of having acute diverticulitis, especially when the disease is not
      severe. The image of an inflamed diverticulum shown at US strongly suggests the
      diagnosis of mild diverticular disease. When diverticulitis is severe, CT should
      be performed in addition to US.

PMID- 7829460
TI  - Esophageal metastasis from breast carcinoma.
AB  - A case of esophageal metastasis from a breast carcinoma is presented. Location
      was, as usual, midesophageal. The interval of time between breast carcinoma and
      the onset of esophageal symptoms was rather long. Barium swallow examination
      enabled correct diagnosis, whereas several series of superficial endoscopical
      biopsies were negative. Diagnosis was confirmed by deep endoscopical biopsy.

PMID- 7829461
TI  - [diagnostic ultrasonography of air in the portal venous system: apropos of a case
      of colonic radionecrosis and literature review].
AB  - We present a case of dramatic radiation enterocolitis inducing portal venous air
      diagnosed by Doppler sonography only. The sonographic pattern consisted of
      multiple irregular hyperechoic areas into the liver, with internal repetitive
      noisy bidirectional peaks superimposed on the usual continuous Doppler display of
      the portal flow. Although portal hyperechoic moving foci alone may reflect only
      slow portal velocity, they do not create any Doppler distortion as do moving
      bubbles. Portal air may have multiple causes such as abdominopelvic abscesses,
      sepsis, intestinal distension, fulminant hepatitis, cholangitis, cholecystitis,
      diabetic acidosis..., but mesenteric infarct, necrotic enterocolitis, and
      radiation enteritis are life-threatening conditions that have to be diagnosed as
      soon as possible. Although large quantities of portal air may be demonstrated on
      plain film of the abdomen or by computed tomography, Doppler sonography may
      detect smaller quantities, allowing earlier diagnosis of intestinal pathology
      requiring immediate surgical treatment. Therefore, Doppler sonography of the
      liver should be performed in any patient with acute abdominal pain or distension,
      especially if being treated by abdominal radiotherapy.

PMID- 7829462
TI  - Colonic gallstone ileus.
AB  - We present a rare case of colonic gallstone obstruction in a patient with
      cholecystocolic fistula. Ultrasound was able to detect the Rigler triad whereas
      plain film initially only showed ileus. Contrast enema and ERCP failed to show a
      biliary-enteric fistula. Only the combination of colonoscopy and contrast
      fistulography evidenced the cholecystocolic connection. The difficulties in
      establishing the correct radiologic diagnosis of gallstone ileus and in
      visualizing the biliary-enteric fistula are discussed.

PMID- 7829463
TI  - [Pulmonary edema secondary to the intravenous administration of iodized contrast.
      A clinical case with high-resolution tomodensitometry studies].
AB  - Contrast media related reactions are numerous and of variable gravity. We report
      a case of pulmonary edema related to the intravenous administration of contrast
      media. Cardiogenic and non cardiogenic pulmonary edema are pathophysiologic
      possibilities. High resolution CT findings associate patchy ground glass areas
      and smooth thickening of subpleural septa, both rapidly disappearing.

PMID- 7829464
TI  - Neonatal cerebral candidiasis: CT findings and clinical correlation.
AB  - Lumbar puncture in a premature newborn undergoing therapy for sepsis revealed
      meningitis. Contrast-enhanced cranial tomography revealed multiple, homogeneously
      or ring-like enhanced lesions with peripheral edema. Cerebrospinal fluid culture
      showed growth of candida. Significant clinical recovery after Amphotericin-B
      treatment was noted. Follow-up CT examination showed regression of the lesions.
      Five months later no pathology was reported except small calcified granulomas and
      an area of encephalomalacia.

PMID- 7829465
TI  - [Diagnosis of an 'apple-core' lesion in the course of a small bowel enema].
AB  - We describe a case of gallbladder carcinoma observed fortuitously during small
      bowel enteroclysis as an "apple-core" lesion. This case illustrates the non
      specificity of the clinical manifestations as well as the usual pitfalls in the
      diagnostic step.

PMID- 7829466
TI  - Aortocaval fistula: CT appearance with pathological correlation.
AB  - Atherosclerotic aneurysm of the abdominal aorta is a frequent finding in a
      general hospital patient population. Most complications such as rupture,
      thrombosis and superinfection are well known. We report on a patient with
      aortocaval fistulization. This rare complication was diagnosed on contrast
      enhanced computed tomography. Pathological correlation was obtained as attempted
      surgery was unsuccessful.

PMID- 7829467
TI  - Cytomegalovirus colitis in a patient with AIDS: CT findings.
AB  - This case report describes an AIDS patient with a cytomegalovirus (CMV) colitis.
      A CT scan of the abdomen showed a thick colonic wall, producing a target sign. CT
      scanning of the abdomen may be useful in patients suspected of CMV rectocolitis
      in order to decide whether a rectosigmoidoscopy or a complete colonoscopy should
      be performed. A definitive diagnosis of CMV rectocolitis can only be made by
      intestinal biopsy.

PMID- 7829468
TI  - [Recurrent lithiasis following cholecystectomy imaged with ultrasonography,
      tomodensitometry and cholangiography].
AB  - It is generally admitted, that after cholecystectomy, the cystic duct and the
      gallbladder remnant may cause symptoms, by being the site of inflammation.
      Recurrence of stones in a reformed gallbladder is avoided when cholecystectomy is
      complete. We report the case of a 43-year-old woman, presenting 19 years after
      cholecystectomy with a reformed gallbladder containing stones demonstrated by US,
      CT and cholangiography.

PMID- 7829469
TI  - Are we using magnetic resonance in a responsible way?

PMID- 7829470
TI  - [Results and analysis of quality control carried out in medical radiodiagnostic
      units in Belgium].
AB  - This report presents the results of a quality control study performed in Belgium
      on 226 conventional X-ray units collected between 1989-1993 and analyses the dose
      rates at the image intensifier inlet of 217 X-ray units. These X-ray units are
      located in public hospitals, private radiological installations clinics, and
      polyclinics.

PMID- 7829471
TI  - [Leiomyoma in the duodenum].

PMID- 7829472
TI  - Isolation of a novel collagen-binding protein from the mushroom, Hypsizigus
      marmoreus, which inhibits the Lewis lung carcinoma cell adhesion to type IV
      collagen.
AB  - A type IV collagen-binding protein of 23 kDa was isolated from the mushroom,
      Hypsizigus marmoreus. This protein, HM 23, bound to type IV and type I collagens
      and gelatin, and to much lesser extent to fibronectin, but not to laminin or
      bovine serum albumin. The adhesion of Lewis lung carcinoma cells was inhibited
      when the type IV collagen substratum was pretreated with HM 23. A computer search
      of the determined partial amino acid sequence indicated no homologous proteins
      reported. These results indicate that HM 23 is a hitherto undescribed fungus
      protein that can interact with animal extracellular matrix proteins.

PMID- 7829473
TI  - Disassembly of Son-of-sevenless proteins from Grb2 during p21ras desensitization
      by insulin.
AB  - Insulin receptor signaling acutely stimulates GTP loading of p21ras, apparently
      by mobilizing complexes of Grb2 and the guanine nucleotide exchangers Son-of
      sevenless (Sos) 1 and 2 to associate with tyrosine-phosphorylated proteins in the
      plasma membrane. Here we show that in 32P-labeled 3T3-L1 adipocytes the elevated
      cellular concentrations of [32P]GTP-bound p21ras in response to insulin return to
      near basal levels after 20-30 min of hormone stimulation, while insulin receptors
      remain activated. Lysates of such desensitized cells were quantitatively
      immunoprecipitated with an antiserum recognizing both Sos1 and Sos2 proteins or a
      specific anti-Sos2 antiserum. Immunoblot analysis of these precipitates revealed
      that insulin causes a marked hyperphosphorylation of Sos1 and a 50% decrease in
      Grb2 associated with Sos proteins under these conditions. Similarly, anti-Grb2
      immunoprecipitates of such lysates revealed the presence of decreased Sos1
      protein due to insulin action. The disassembly of Grb2 from Sos proteins slightly
      precedes the time course of p21ras deactivation in response to insulin. These
      data are consistent with the hypothesis that the dissociation of Grb2 from Sos
      proteins caused by insulin in 3T3-L1 cells mediates p21ras deactivation and
      desensitization.

PMID- 7829474
TI  - Construction and function of chimeric beta subunits containing regions from the
      beta subunits of the F1F0 ATPases of Escherichia coli and Bacillus megaterium.
AB  - The highly conserved beta subunit of the Escherichia coli F1F0 ATPase was divided
      into three sections, each of which was exchanged with the homologous section of
      the beta subunit of the obligate aerobe Bacillus megaterium. Plasmids coding for
      the resultant six chimeric beta subunits varied in their abilities to complement
      two E. coli beta mutants as measured by testing transformed cells for aerobic
      growth on a nonfermentable carbon source or anaerobic growth on rich medium
      containing glucose. Two chimeras were able to restore both growth on succinate
      and anaerobic growth on rich medium. The genetic results corresponded to
      increased levels of membrane-bound ATPase and ATP synthase activities. These
      chimeric subunits were therefore capable of being assembled into functional E.
      coli ATPase complexes. The results indicate that chimeric beta subunits can be
      used to analyze assembly of the beta subunit and that the final 181 amino acids
      of the beta subunit might contain a region involved in functional energy
      coupling.

PMID- 7829475
TI  - Non-peptide angiotensin agonist. Functional and molecular interaction with the
      AT1 receptor.
AB  - Non-peptide ligands for peptide receptors for the G-protein-coupled type are
      generally antagonists, except in the opiate system. Recently, it was observed
      that a subset of biphenylimidazole derivatives surprisingly possessed angiotensin
      like activity in vivo. In COS-7 cells transfected with the rat AT1 receptor a
      prototype of these compounds, L-162,313 stimulated phosphoinositide hydrolysis
      with an EC50 of 33 +/- 11 nM. The maximal response to the compound was 50% of
      that of angiotensin II in COS-7 cells but only 3% in stably transfected Chinese
      hamster ovary cells. The agonistic effect of L-162,313 was blocked by the AT1
      specific antagonist L-158,809 and was not observed in untransfected cells. In
      Chinese hamster ovary cells, L-162,313 also acted as an insurmountable antagonist
      of the angiotensin stimulated phosphoinositide hydrolysis. In contrast to
      previously tested non-peptide ligands, L-162,313 bound with reasonably high
      affinity to the Xenopus laevis AT1 receptor. In the human receptor, the binding
      of L-162,313 was found to be unaffected by point mutations in transmembrane
      segments III and VII, which impaired the binding of biphenylimidazole
      antagonists. Substitutions in the extracellular domains of the human and rat
      receptor, which impaired the binding of angiotensin II, did not affect the
      binding of L-162,313. It is concluded that a subset of biphenylimidazole
      compounds can act as high affinity partial agonists on the AT1 receptor. These
      compounds have molecular interactions with the receptor which appear to differ
      both from that of the structurally similar non-peptide antagonists and from that
      of their functional counterpart, the peptide agonist.

PMID- 7829476
TI  - The sialyltransferase "sialylmotif" participates in binding the donor substrate
      CMP-NeuAc.
AB  - All members of the sialyltransferase gene family cloned to date contain a
      conserved region, the "sialylmotif," consisting of 48-49 amino acids in the
      center of the coding sequence. To investigate the function of this motif, mutant
      constructs of the Gal beta 1,4GlcNAc alpha 2,6-sialyltransferase were designed by
      site-directed mutagenesis, replacing 11 individual conserved amino acids with
      alanine. Each of the mutants was expressed in COS-1 cells, and eight of these
      retained sialyltransferase activity, allowing comparison of their enzymatic
      properties with that of the wild type enzyme. Kinetic analysis showed that six of
      eight mutants had a 3-12-fold higher Km for the donor substrate CMP-NeuAc
      relative to the wild type enzyme, while the Km values for the acceptor substrate
      were within 0.5-1.2-fold of the wild type for all eight mutants evaluated. The Ki
      of the donor substrate analog CDP was also evaluated for the recombinant
      sialyltransferase with the Val to Ala mutation at residue 220, which produced a 6
      fold increase in Km of CMP-NeuAc. A corresponding increase in Ki of 3.4-fold was
      observed for CDP, indicating a decreased affinity for the cytidine nucleotide.
      Taken together, these results suggest that the conserved sialylmotif in the
      sialyltransferase gene family participates in the binding of the common donor
      substrate, CMP-NeuAc.

PMID- 7829477
TI  - Binding of divalent cation and nucleotide to G-actin in the presence of profilin.
AB  - The effect of profilin, a G-actin binding protein, on the mechanism of exchange
      of the tightly bound metal ion and nucleotide on G-actin, has been investigated.
      1) In low ionic strength buffer, profilin increases the rates of Ca2+ and Mg2+
      dissociation from G-actin 250- and 50-fold, respectively. On the profilin-actin
      complex as well as on G-actin alone, nucleotide exchange is dependent on the
      concentration of divalent metal ion and is kinetically limited, at low
      concentration of metal ion, by the dissociation of the metal ion. 2) Under
      physiological ionic conditions, nucleotide exchange on G-actin is 1 order of
      magnitude faster than at low ionic strength. The rate of MgATP dissociation is
      increased by profilin from 0.05 s-1 to 2 s-1, the rate of MgADP dissociation is
      increased from 0.2 s-1 to 24 s-1. The dependences of the exchange rates on
      profilin concentration are consistent with a high affinity (5 x 10(6) to 10(7) M
      1) of profilin for ATP-G-actin, and a 20-fold lower affinity for ADP-G-actin.
      Profilin binding to actin lowers the affinity of metal-nucleotide by about 1
      order of magnitude. These results restrain the possible roles of profilin in
      actin assembly in vivo.

PMID- 7829478
TI  - Tracing hepatic gluconeogenesis relative to citric acid cycle activity in vitro
      and in vivo. Comparisons in the use of [3-13C]lactate, [2-13C]acetate, and alpha
      keto[3-13C]isocaproate.
AB  - The validity of the use of a carbon tracer for investigating liver intermediary
      metabolism in vivo requires that the labeling pattern of liver metabolites not be
      influenced by metabolism of the tracer in other tissues. To identify such
      specific tracer, livers from 48-h starved rats were perfused with recirculating
      buffer containing [3-13C]lactate, [2-13C]acetate, or alpha-keto[3
      13C]isocaproate. Conscious 48-h starved rats were infused with the same tracers
      for 5 h. The labeling patterns of liver glutamate and extracellular glucose were
      assayed by gas chromatography-mass spectrometry. In vivo data were corrected for
      13CO2 reincorporation into C-1 of glutamate and C-3 and C-4 of glucose, using
      data from control rats infused with NaH13CO3. With [3-13C]lactate the labeling
      pattern of liver glutamate was the same in perfused organs and in vivo. In
      contrast, with [2-13C]acetate and alpha-keto[3-13C]isocaproate the labeling
      pattern of liver glutamate in vivo was clearly influenced by the expected
      labeling pattern of citric acid cycle intermediates formed in non-gluconeogenic
      organs, presumably glutamine made in muscle. Indeed, the labeling pattern of
      plasma glutamine and liver glutamate were similar in experiments with [3
      13C]lactate but different in experiments with [2-13C]acetate and alpha-keto[3
      13C]isocaproate. Similar conclusions were drawn from the labeling patterns of
      glucose. Therefore, labeled lactate appears as the best tracer for studies of
      liver intermediary metabolism in vivo. Our data also show that a substantial
      fraction of alpha-ketoisocaproate metabolism occurs in peripheral tissues.

PMID- 7829479
TI  - GATA-3 dominant negative mutant. Functional redundancy of the T cell receptor
      alpha and beta enhancers.
AB  - The GATA family of transcription factors regulates a wide variety of genes,
      including those involved in differentiation of erythrocytes and T lymphocytes. We
      report here the creation of a dominant negative mutant of GATA-3, KRR, which
      effectively blocks wild-type GATA-1, GATA-2, and GATA-3 transactivation when co
      expressed in transient assays. KRR was generated by site-directed mutagenesis
      while investigating a putative activation domain of GATA-3, located between its
      two zinc fingers. The GATA-3 KRR mutation does not affect expression, nuclear
      translocation, or the ability to bind to a consensus GATA sequence. KRR can
      suppress the activity of the minimal T cell receptor (TCR) alpha and beta
      enhancers by 12- and 3.4-fold, respectively. However, KRR did not have a
      significant effect on the activity of larger TCR-alpha and -beta enhancer
      fragments. Thus, functional redundancy in the TCR-alpha and -beta enhancers can
      compensate for the loss of GATA-3 activity.

PMID- 7829480
TI  - Cloning, purification, and properties of a novel NADH pyrophosphatase. Evidence
      for a nucleotide pyrophosphatase catalytic domain in MutT-like enzymes.
AB  - An Escherichia coli open reading frame containing significant homology to the
      active site of the MutT enzyme codes for a novel dinucleotide pyrophosphatase.
      The motif shared by these two proteins and several others is conserved throughout
      nature and may designate a nucleotide-binding or pyrophosphatase domain. The E.
      coli NADH pyrophosphatase has been cloned, overexpressed, and purified to near
      homogeneity. The protein contains 257 amino acids (M(r) = 29,774) and migrates on
      gel filtration columns as an apparent dimer. The enzyme catalyzes the hydrolysis
      of a broad range of dinucleotide pyrophosphates, but uniquely prefers the reduced
      form of NADH. The Vmax/Km for NADH (69 mumol min-1 mg-1 mM-1) is an order of
      magnitude higher than for any other dinucleotide pyrophosphate tested. In
      addition, the Km for NADH (0.1 mM) is 50-fold lower than the Km for NAD+. The
      hydrolysis of dinucleotide pyrophosphates requires divalent metal ions and yields
      two mononucleoside 5'-phosphates. The metals that most efficiently stimulate
      activity are Mg2+ and Mn2+. Although these metals support similar Vmax values at
      optimal metal concentration, the apparent Km for Mg2+ is 3.7 mM (at 1 mM NADH),
      whereas the apparent Km for Mn2+ at the same NADH concentration is 30 microM.

PMID- 7829481
TI  - Hydrophobic surfaces that are hidden in chaperonin Cpn60 can be exposed by
      formation of assembly-competent monomers or by ionic perturbation of the
      oligomer.
AB  - The oligomeric form (14-mer) of the chaperonin protein, Cpn60 (GroEL) from
      Eschericia coli, displays restricted hydrophobic surfaces and binds tightly one
      to two molecules of the fluorescent hydrophobic reporter, 1,1'-bi(4
      anilino)naphthalene-5,5'-disulfonic acid (bisANS). The 14-mer is resistant to
      proteolysis by chymotrypsin, and none of the three sulfhydryl groups/monomer
      react with 6-iodoacetamidofluorescein. When monomers of Cpn60 that are folded and
      competent to participate in protein folding are formed by low concentrations of
      urea (< 2.5 M), the hydrophobic exposure increases to accommodate approximately
      14 molecules of bisANS/14-mer, the binding affinity for bisANS decreases, and 1
      sulfhydryl group/monomer reacts with 6-iodoacetamidofluorescein. These monomers
      display limited proteolysis by chymotrypsin at several points within a
      hydrophobic sequence centered around residue 250 to produce a relatively stable N
      terminal fragment (approximately = to 26 kDa) and a partially overlapping C
      terminal fragment (approximately = to 44 kDa). The exposure of hydrophobic
      surfaces is facilitated by ATPMg. Ions increase hydrophobic exposure more
      effectively than urea without dissociation of Cpn60. For example, subdenaturing
      concentrations of guanidinium chloride (< or = 0.75 M) or the stabilizing salt,
      guanidinium sulfate, as well as NaCl or KCl are effective. The trivalent cation,
      spermidine, induces maximum exposure at 5 mM. The results suggest that
      hydrophobic surfaces can be involved in stabilizing the oligomer and/or in
      binding proteins to be folded, and they are consistent with suggestions that
      amphiphilic structures, presenting hydrophobic surfaces within a charged context,
      would be particularly effective in binding to Cpn60.

PMID- 7829482
TI  - Expression of the extracellular domain of the thyrotropin receptor in the
      baculovirus system using a promoter active earlier than the polyhedrin promoter.
      Implications for the expression of functional highly glycosylated proteins.
AB  - Conventional baculovirus vectors that utilize the very late polyhedrin promoter
      have not proved successful for expressing a thyrotropin (TSH) receptor capable of
      ligand and Graves' disease autoantibody binding comparable to the receptor
      produced in mammalian cells. Because of the clinical importance of high level
      expression of this protein, we reassessed the baculovirus system using a new
      transfer vector (pAcMP3) containing the late basic protein promoter, which
      functions earlier than the classical polyhedrin promoter. Maximal synthesis of
      the [35S]methionine-labeled TSH receptor extracellular domain, affinity-purified
      using a 6-histidine tag, occurred earlier (1 day after insect cell infection)
      than with a vector (pVL1393) containing the polyhedrin promoter. The pAcMP3
      derived TSH receptor extracellular domain was larger (approximately 68 kDa) than
      the pVL1393-derived protein (approximately 63 kDa). Only the 68-kDa product was
      secreted, albeit in trace amounts detectable only by precursor labeling.
      Enzymatic deglycosylation reduced both 68- and 63-kDa cellular proteins to
      approximately 54 kDa, indicating that the pAcMP3 vector generated a protein with
      greater carbohydrate content. However, despite its greater degree of
      glycosylation, most of the 68-kDa protein remained within the cell, almost
      entirely in the particulate fraction. Remarkably, the trace amounts of 68-kDa
      receptor protein affinity-purified from the soluble cytosolic fraction of
      infected insect cells completely neutralized TSH receptor autoantibodies in
      patients' sera and partly inhibited TSH binding. In conclusion, a baculovirus
      vector with a promoter active earlier than the conventional polyhedrin promoter
      generates a more glycosylated and functional TSH receptor extracellular domain
      protein, albeit at low levels. These data carry important implications for the
      expression by baculovirus vectors of functional, highly glycosylated proteins.

PMID- 7829483
TI  - The vaccinia virus A18R gene product is a DNA-dependent ATPase.
AB  - The predicted amino acid sequence of the vaccinia virus gene A18R shows
      significant homology to the human ERCC3 gene product, which is a member of the
      DEXH subfamily of the DNA and RNA helicase superfamily II and which plays a role
      in both RNA polymerase II transcription and nucleotide excision repair of DNA.
      The vaccinia virus A18R gene product is expressed throughout infection and is
      encapsidated in virions. Vaccinia virions containing mutant A18R gene product are
      defective in early viral transcription in vitro, and infection with A18R mutant
      virus results in aberrant viral transcription late during infection. Thus we
      hypothesize that the vaccinia virus A18R gene product is a helicase that plays a
      role in viral transcription and possibly DNA repair. As a first test of this
      hypothesis, we have affinity purified an amino-terminal polyhistidine-tagged A18R
      protein and shown that it has DNA-dependent ATPase activity. The A18R ATPase
      activity is stimulated by both single-stranded and double-stranded DNA and by
      RNA.DNA hybrids, but not by either single-stranded or double-stranded RNA.

PMID- 7829484
TI  - The vacuolar ATPase: sulfite stabilization and the mechanism of nitrate
      inactivation.
AB  - Using vacuolar membranes from Neurospora crassa, we observed that sulfite
      prevented the loss of vacuolar ATPase activity that otherwise occurred during 36
      h at room temperature. Sulfite neither activated nor changed the kinetic behavior
      of the enzyme. Further, in the presence of sulfite, the vacuolar ATPase was not
      inhibited by nitrate. We tested the hypothesis that sulfite acts as a reducing
      agent to stabilize the enzyme, while nitrate acts as an oxidizing agent,
      inhibiting the enzyme by promoting the formation of disulfide bonds. All reducing
      agents tested, dithionite, selenite, thiophosphate, dithiothreitol and
      glutathione, prevented the loss of ATPase activity. On the other hand, all
      oxidizing agents tested, bromate, iodate, arsenite, perchlorate, and hydrogen
      peroxide, were potent inhibitors of ATPase activity. The inhibitory effect of the
      oxidizing agents was specific for the vacuolar ATPase. The mitochondrial ATPase,
      assayed under identical conditions, was not inhibited by any of the oxidizing
      agents. Analysis of proteins with two-dimensional gel electrophoresis indicated
      that nitrate can promote the formation of disufide bonds between proteins in the
      vacuolar membrane. These data suggest a mechanism to explain why nitrate
      specifically inhibits vacuolar ATPases, and they support the proposal by Feng and
      Forgac (Feng, Y., and Forgac, M. (1994) J. Biol. Chem. 269, 13244-13230) that
      oxidation and reduction of critical cysteine residues may regulate the activity
      of vacuolar ATPases in vivo.

PMID- 7829485
TI  - Inhibition of clathrin assembly by high affinity binding of specific inositol
      polyphosphates to the synapse-specific clathrin assembly protein AP-3.
AB  - Bacterially expressed synapse-specific clathrin assembly protein, AP-3 (F1
      20/AP180/NP185/pp155), bound with high affinity both inositol hexakisphosphate
      (InsP6) (Kd = 239 nM) and diphosphoinositol pentakisphosphate (PP-InsP5) (Kd = 22
      nM). The specificity of this ligand binding was demonstrated by competitive
      displacement of bound [3H]InsP6. IC50 values were as follows: PP-InsP5 = 50 nM,
      InsP6 = 240 nM, inositol-1,2,4,5,6-pentakisphosphate (Ins(1,2,4,5,6)P5) = 2.2
      microM, inositol-1,3,4,5,6-pentakisphosphate (Ins(1,3,4,5,6)P5) = 5 microM,
      inositol-1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P4) > 10 microM, inositol-1,4,5
      trisphosphate (Ins(1,4,5)P3) > 10 microM. Moreover, 10 microM inositol
      hexasulfate (InsS6) displaced only 15% of [3H]InsP6. The physiological
      significance of this binding is the ligand-specific inhibition of clathrin
      assembly (PP-InsP5 > InsP6 > Ins(1,2,4,5,6)P5); Ins(1,3,4,5,6)P5 and InsS6 did
      not inhibit clathrin assembly. We also observed high affinity binding of InsP6 to
      purified bovine brain AP-3. We separately expressed the 33-kDa amino terminus and
      the 58-kDa carboxyl terminus, and it was the former that contained the high
      affinity inositol polyphosphate binding site. These studies suggest that specific
      inositol polyphosphates may play a role in the regulation of synaptic function by
      interacting with the synapse-specific clathrin assembly protein AP-3.

PMID- 7829486
TI  - Transport of beta-casein-derived peptides by the oligopeptide transport system is
      a crucial step in the proteolytic pathway of Lactococcus lactis.
AB  - In the proteolytic pathway of Lactococcus lactis, milk proteins (caseins) are
      hydrolyzed extracellularly to oligopeptides by the proteinase (PrtP). The fate of
      these peptides, i.e. extracellular hydrolysis followed by amino acid uptake or
      transport followed by intracellular hydrolysis, has been addressed. Mutants have
      been constructed that lack a functional di-tripeptide transport system (DtpT)
      and/or oligopeptide transport system (Opp) but do express the P1-type proteinase
      (specific for hydrolysis of beta- and to a lesser extent kappa-casein). The wild
      type strain and the DtpT- mutant accumulate all beta-casein-derived amino acids
      in the presence of beta-casein as protein substrate and glucose as a source of
      metabolic energy. The amino acids are not accumulated significantly inside the
      cells by the Opp- and DtpT- Opp- mutants. When cells are incubated with a mixture
      of amino acids mimicking the composition of beta-casein, the amino acids are
      taken up to the same extent in all four strains. Analysis of the extracellular
      peptide fraction, formed by the action of PrtP on beta-casein, indicates that
      distinct peptides disappear only when the cells express an active Opp system.
      These and other experiments indicate that (i) oligopeptide transport is essential
      for the accumulation of all beta-casein-derived amino acids, (ii) the activity of
      the Opp system is sufficiently high to support high growth rates on beta-casein
      provided leucine and histidine are present as free amino acids, and (iii)
      extracellular peptidase activity is not present in L. lactis.

PMID- 7829487
TI  - Structural characterization of a diuretic peptide from the central nervous system
      of the leech Erpobdella octoculata. Angiotensin II Amide.
AB  - Purification of a material immunoreactive to an antiserum against angiotensin II
      and present in the central nervous system of the pharyngobdellid leech Erpobdella
      octoculata was performed by reversed-phase high pressure liquid chromatography
      combined with both enzyme-linked immunosorbent assay and dot immunobinding assays
      for angiotensin II. Establishment of the amino acid sequence by Edman
      degradation, electrospray, and fast atom bombardement mass spectrometry
      measurements and enzymatic treatment by carboxypeptidase A indicated that this
      "central" angiotensin II-like material, the first one fully characterized in the
      animal kingdom, is an angiotensin II amide. This finding constitutes also the
      first biochemical characterization of a peptide of the angiotensin family in an
      invertebrate. Synthetic angiotensin II amide exerts, when injected in leeches, a
      diuretic effect and is, 1 and 2 h postinjection, 100-fold more potent than
      vertebrate angiotensin II. An identification of the proteins immunoreactive to an
      antiserum against angiotensin II performed at the level of both central nervous
      system extracts and in vitro central nervous system-translated RNA products
      indicated that in the two cases, two proteins were detected. Their molecular
      masses, which were, respectively, approximately 14 and approximately 18 kDa for
      the central nervous system extracts and approximately 15 and approximately 19 kDa
      for in vitro central nervous system-translated RNA products, differ from that of
      angiotensinogen (approximately 60 kDa), the precursor of vertebrate angiotensin
      II.

PMID- 7829488
TI  - Molecular characterization of an apical early endosomal glycoprotein from
      developing rat intestinal epithelial cells.
AB  - The apical endosomal compartment is thought to be involved in the sorting and
      selective transport of receptors and ligands across polarized epithelia. To learn
      about the protein components of this compartment, we have isolated and sequenced
      a cDNA that encodes a glycoprotein that is located in the apical endosomal
      tubules of developing rat intestinal epithelial cells. The deduced amino acid
      sequence predicts a protein of 1216 amino acids with a molecular mass of 133,769
      Da. The deduced amino acid sequence together with amino-terminal amino acid
      sequencing indicate that there is a cleaved 21-amino acid signal sequence at the
      NH2-terminal portion of the molecule. There is a single hydrophobic region near
      the carboxyl terminus that has the characteristics of a membrane-spanning domain
      and a 36-amino acid cytoplasmic tail. We have found that the major form of this
      protein in intestinal epithelial cells has a molecular mass of 55-60 kDa, which
      is significantly smaller than the size predicted from the cDNA sequence,
      suggesting that the protein is synthesized as a large precursor and processed to
      the smaller form. The smaller form remains associated with the membrane, however,
      possibly through noncovalent association with the transmembrane portion of the
      molecule or with another membrane protein. The extracytoplasmic domain is
      cysteine-rich, with three cysteine-rich repeats that are similar to cysteine
      repeats present in several receptor proteins. However, there is no other
      significant similarity to other proteins in the GenBank. The cytoplasmic tail
      contains a possible internalization motif and several consensus motifs for
      serine/threonine kinases. Northern blot analysis suggests a single abundant
      message, and Southern blot analysis is consistent with a single gene and the
      absence of pseudogenes for this unique endosomal protein.

PMID- 7829489
TI  - A difference infrared study of hydrogen bonding to the Z. tyrosyl radical of
      photosystem II.
AB  - Photosystem II, the photosynthetic water oxidizing complex, contains two well
      characterized redox active tyrosines, D and Z. D forms a stable radical of
      unknown function. Z is an electron carrier between the primary chlorophyll donor
      and the manganese catalytic site. The vibrational difference spectra associated
      with the oxidation of tyrosines Z and D have been obtained through the use of
      infrared spectroscopy (MacDonald, G. M., Bixby, K.A., and Barry, B.A. (1993)
      Proc. Natl. Acad. Sci. U.S.A. 90, 11024-11028). Here, we examine the effect of
      deuterium exchange on these vibrational difference spectra. While the putative C
      O vibration of stable tyrosine radical D. downshifts in 2H2O, the putative C-O
      vibration of tyrosine radical Z. does not. This result is consistent with the
      existence of a hydrogen bond to the phenol oxygen of the D. radical; we conclude
      that a hydrogen bond is not formed to the Z. radical. In an effort to identify
      the amino acid residue that is the proton acceptor for Z, we have performed
      global 15N labeling. While significant 15N shifts are observed in the vibrational
      difference spectrum, substitution of a glutamine for a histidine that is
      predicted to lie in the environment of tyrosine Z has little or no effect on the
      difference infrared spectrum. There is also no significant change in the yield or
      lineshape of the Z. EPR signal under continuous illumination in this mutant. Our
      results are inconsistent with the possibility that this residue, histidine 190 of
      the D1 polypeptide, acts as the sole proton acceptor for tyrosine Z.

PMID- 7829490
TI  - Regulation of the DNA methyltransferase by the Ras-AP-1 signaling pathway.
AB  - Using deletion analysis and site-specific mutagenesis to map the 5' regulatory
      region of the DNA methyltransferase (MeTase) gene, we show that a 106-bp sequence
      (at -1744 to -1650) bearing three AP-1 sites is responsible for induction of DNA
      MeTase promoter activity. Using transient cotransfection chloramphenicol acetyl
      transferase assays in P19 cells, we show that the DNA MeTase promoter is induced
      by c-Jun or Ha-Ras but not by a dominant negative mutant of Jun, delta 9. The
      activation of the DNA MeTase promoter by Jun is inhibited in a ligand dependent
      manner by the glucocorticoid receptor. Stable expression of Ha-Ras in P19 cells
      results in induction of transcription of the DNA MeTase mRNA as determined by
      nuclear run-on assays and the steady state levels of DNA MeTase mRNA as
      determined by an RNase protection assay. These experiments establish a potential
      molecular link between nodal cellular signaling pathways and the control of
      expression of the DNA MeTase gene. This provides us with a possible molecular
      explanation for the hyperactivation of DNA MeTase in many cancer cells and
      suggests that DNA MeTase is one possible downstream effector of Ras.

PMID- 7829491
TI  - Effect of the arrangement of tandem repeating units of class A amphipathic alpha
      helixes on lipid interaction.
AB  - Exchangeable apolipoproteins possess tandem repeating units of class A
      amphipathic helical segments and many of them are linked together by proline
      residues. To understand the optimal arrangement of the amphipathic helixes for
      lipid association, we have studied the interactions of three model class A
      amphipathic helical peptides with lipids. The three peptides are: 37pA, a dimer
      of 18A (DWLKAFYDKVAEKLKEAF) linked together by a Pro (18A-Pro-18A); 37aA, a dimer
      of 18A linked together by an Ala (18A-Ala-18A); and 36A, a dimer of 18A without
      any linker residue (18A-18A). Circular dichroism (CD) spectra showed that the
      peptides are predominantly alpha-helical in aqueous and lipid environments.
      Temperature dependent CD studies indicated that in buffer helix stability
      decreases in the order 36A > 37aA > 37pA; however, in the presence of dimyristoyl
      phosphatidylcholine (DMPC), the above order is reversed. The retention times of
      the peptides on a C18 reversed-phase high performance liquid chromatography
      column decreased in the order 36A > 37aA > 37pA, consistent with the lengths of
      the nonpolar faces of the alpha-helixes being in the same order; the retention
      time of the parent 18A was shorter than 37pA. While 37pA adsorbed to egg
      phosphatidylcholine monolayers most strongly, the degree and rate of association
      of 36A were significantly lower. Differential scanning calorimetry indicated
      that, while 37pA was most effective in reducing the enthalpy of the gel to liquid
      crystalline phase transition of DMPC multilamellar vesicles, 36A was least
      effective; 36A was even less effective than 18A. Fluorescence quenching
      experiments with iodide and acrylamide indicated that, in the presence of DMPC,
      Trp residues in 36A are most exposed to the quenchers while in 37pA they are
      least exposed. In the presence of DMPC, shielding of Trp in 18A from the
      quenchers was more than that observed with Trp residues in 36A. The results of
      this study suggest that the arrangement of tandem repeating amphipathic helical
      units which results in the formation of a class A amphipathic helix with a
      nonpolar face longer than five or six turns reduces the ability of the helix to
      associate with phospholipid.

PMID- 7829492
TI  - Contribution of the transforming growth factor alpha B-loop beta-sheet to binding
      and activation of the epidermal growth factor receptor.
AB  - We have exploited the differences in binding affinities of the chicken epidermal
      growth factor (EGF) receptor for EGF and transforming growth factor alpha (TGF
      alpha) to study the role of the B-loop beta-sheet of these ligands in receptor
      recognition and activation. Although EGF and TGF alpha share similar secondary
      and tertiary structures imposed by three highly conserved intramolecular
      disulfide bonds, they have only 30-40% overall sequence identity. The B-loop beta
      sheet is the major structural element in EGF and TGF alpha, but sequence
      similarity in this region is low. To investigate its role in receptor binding, we
      constructed two chimeric growth factors (mEGF/hTGF alpha 21-30 and mEGF/hTGF
      alpha 21-32) composed of the murine EGF (mEGF) amino acid sequence with residues
      21-30 of the B-loop beta-sheet replaced by the equivalent residues of human TGF
      alpha (hTGF alpha); in chimera mEGF/hTGF alpha 21-32, asparagine 32, which lies
      at the boundary of the amino and carboxyl domains of mEGF, was also replaced by
      its hTGF alpha counterpart (valine). In initial studies using unpurified medium,
      it was found that the recombinant growth factors exhibited differing mitogenic
      potencies (mEGF/hTGF alpha 21-32 > mEGF/hTGF alpha 21-30 > mEGF) when assayed on
      chicken fibroblasts, even though they were equivalent in mitogenesis assays using
      cells expressing the human EGF receptor. After purification, mEGF/hTGF alpha 21
      32 was found to be 50 times more potent than mEGF in the chick fibroblast
      mitogenesis assay and exhibited a 10-fold increase in relative affinity for the
      chicken EGF receptor; both growth factors still exhibited equivalent mitogenic
      and receptor binding activity when tested on cells expressing human EGF
      receptors. We conclude that the B-loop beta-sheet of hTGF alpha is an important
      determinant of EGF receptor binding affinity and biological activity.

PMID- 7829493
TI  - Spectroscopic and kinetic studies on reaction of cytochrome P450nor with nitric
      oxide. Implication for its nitric oxide reduction mechanism.
AB  - Cytochrome P450 purified from Fusarium oxysporum (P450nor) is a unique heme
      enzyme that catalyzes the reduction of nitric oxide to nitrous oxide with
      electrons directly transferred from NADH (2NO + NADH + H+--> N2O + H2O + NAD+).
      We studied the reaction of P450nor with NO and NADH using stopped-flow rapid scan
      and low temperature spectroscopic methods. The NO ligand can bind to the ferric
      enzyme to form the stable NO bound complex, P450nor(Fe3+NO). Reduction of
      P450nor(Fe3+NO) with NADH yielded an intermediate, which transiently formed (tau
      = approximately 100 ms) and spontaneously decomposed to the Fe3+ state. The
      optical absorption spectrum of the intermediate was different from that of
      P450nor(Fe2+NO), which was formed by either a one-electron reduction of
      P450nor(Fe3+NO) with Na2S2O4 or NO binding to P450nor(Fe2+). On the basis of
      these observations, we suggested that the intermediate is presumably a two
      electron reduced product of P450nor(Fe3+NO) by NADH, formally the (Fe3+NO)2
      complex. We determined the rate constants of these reactions at 10 degrees C for
      the NO binding to P450nor(Fe3+) (2.6 x 10(7) M-1 s-1), the NADH reduction of
      P450nor(Fe3+NO) (0.9 x 10(6) M-1 s-1), and the spontaneous decomposition of the
      intermediate (0.027 s-1). In these kinetic measurements, it was found that the
      former two processes are fast enough, while the latter is extremely slow,
      compared with the fast turnover of the catalytic reaction (1200 s-1 at 10 degrees
      C), which we measured by monitoring the NADH consumption. Therefore, we suggested
      that in the catalytic cycle, decomposition of the intermediate is fairly
      accelerated by free NO, resulting in such a fast turnover. On the basis of
      several lines of the spectroscopic and the kinetic evidence, we proposed a
      possible mechanism of the NO reduction by P450nor.

PMID- 7829494
TI  - ADP-ribosylation of Rhizobium meliloti glutamine synthetase III in vivo.
AB  - The control of glutamine synthetase (GS), the first enzyme in the main pathway
      used by Rhizobium meliloti to assimilate ammonia, is central to cellular nitrogen
      metabolism. R. meliloti is unusual in having three distinct types of GS,
      including a unique GS, GSIII, that differs considerably from both GSI, which
      resembles other bacterial GS proteins and GSII, which resembles the GS found in
      eukaryotes. We show here that GSIII can be post-translationally modified in vivo
      by ADP-ribosylation at an arginine residue. 32PO4 attached to GSIII during
      bacterial growth as part of the modifying group could be removed by treatment
      with snake venom phosphodiesterase or by turkey erythrocyte ADP-ribosylarginine
      hydrolase. Treatment of modified GSIII with hydroxylamine at neutral pH releases
      a chromophore that has the retention time of ADP-ribose when analyzed by reversed
      phase high performance liquid chromatography. ADP-ribosylation inhibits GSIII
      activity.

PMID- 7829495
TI  - Inefficient membrane targeting, translocation, and proteolytic processing by
      signal peptidase of a mutant preproparathyroid hormone protein.
AB  - A preproparathyroid hormone allele from a patient with familial isolated
      hypoparathyroidism was shown to have a single point mutation in the hydrophobic
      core of the signal sequence. This mutation, changing a cysteine to an arginine
      codon at the -8 position of the signal peptide, was associated with deleterious
      effects on the processing of preproparathyroid hormone to proparathyroid hormone
      in vitro. To examine the biochemical consequence(s) of this mutation, proteins
      produced by cell-free translation of wild-type and mutant cRNAs were used in
      assays that reconstitute the early steps of the secretory pathway. We find that
      the mutation impairs interaction of the nascent protein with signal recognition
      particle and the translocation machinery. Moreover, cleavage of the mutant signal
      sequence by solubilized signal peptidase is ineffective. The consequence of this
      mutation on processing and secretion of parathyroid hormone is confirmed in
      intact cells by pulse-chase experiments following transient expression of the
      mutant protein in COS-7 cells. The inability of the mutant signal sequence,
      however, to interfere with the targeting and processing of other secreted
      proteins does not support obstruction of the translocation apparatus as the
      mechanism underlying the dominant mode of inheritance of hypoparathyroidism in
      this family.

PMID- 7829496
TI  - Ultraviolet resonance Raman studies of quaternary structure of hemoglobin using a
      tryptophan beta 37 mutant.
AB  - Environmental changes of tyrosine and tryptophan residues of hemoglobin (Hb) upon
      its T to R transition of quaternary structure were investigated with ultraviolet
      resonance Raman (UVRR) spectroscopy excited at 235 nm. DeoxyHb A (T-form) showed
      a UVRR spectrum distinctly different from those of the ligated Hbs (R-form)
      including oxyHb, COHb, and metHb A, whereas the ligated Hbs exhibited similar
      UVRR spectra irrespective of the ligand species and the oxidation state of the
      heme. To characterize the spectral change of Trp-beta 37 at the alpha 1 beta 2
      interface due to the quaternary structure transition, the UVRR spectra of Hb A
      were compared with the corresponding spectra of Hb Hirose (Trp-beta 37-->Ser). A
      difference spectrum between deoxyHb A and deoxyHb Hirose showed only Trp
      resonance Raman (RR) bands, which were reasonably ascribed to Trp-beta 37 in
      deoxyHb A. RR bands at 873 cm-1 (W17) and at 1360 and 1343 cm-1 (W7, Fermi
      doublet) indicated that the indole ring of Trp-beta 37 in deoxyHb A formed a
      strong hydrogen bond at the N1H site in hydrophobic environments. Tyr residues in
      deoxyHb Hirose seemed to be in the same environments as those of deoxyHb A. In
      contrast, the difference spectrum between Hb A and Hb Hirose in the ligated state
      displayed peaks for RR bands of both Trp and Tyr. The difference spectra were
      unaltered by the addition of 5 mM inositol hexaphosphate. This means that the
      differences were not caused by the tetramer to dimer dissociation but by a
      conformation change within a tetramer. Comparison of the Hb A-Hb Hirose
      difference spectra in the oxy and deoxy states revealed that the oxygenation
      induced changes of Trp RR bands arose mostly from Trp-beta 37 with the small
      portion of remaining changes coming from Trp-beta 15, demonstrating that Trp-beta
      37 plays a pivotal role in the quaternary structural change in Hb A.

PMID- 7829497
TI  - P450c11B3 mRNA, transcribed from a third P450c11 gene, is expressed in a tissue
      specific, developmentally, and hormonally regulated fashion in the rodent adrenal
      and encodes a protein with both 11-hydroxylase and 18-hydroxylase activities.
AB  - The rat genome contains four P450c11 genes. One of these (CYP11B1) encodes
      P450c11 beta, which is the steroid 11 beta-hydroxylase found solely in the
      adrenal zona fasciculata/reticularis, and is responsible for the conversion of 11
      deoxycorticosterone to corticosterone. A second P450c11 gene (CYP11B2) encodes
      P450c11AS, which is the aldosterone synthase found solely in the adrenal zona
      glomerulosa. P450c11AS has three activities, 11 beta-hydroxylase, 18-hydroxylase,
      and 18-oxidase, and is responsible for the conversion of 11-deoxycorticosterone
      to aldosterone. Recently, two more rat P450c11 genes, P450c11B3 and P450c11B4,
      were cloned. P450c11B4 appears to be a pseudogene, as two exons are replaced by
      unrelated DNA. P450c11B3 closely resembles P450c11 beta in mRNA and encoded amino
      acid sequences, predicting a protein of 498 amino acids. However, the expression
      of this mRNA and protein have not been demonstrated to date. We now demonstrate
      that this P450c11B3 mRNA is expressed in the adrenal gland several days after
      birth and is not expressed during fetal development or in the adult rat adrenal.
      Like P450c11 beta mRNA, P450c11B3 mRNA is expressed in the zona
      fasciculata/reticularis and not in the zona glomerulosa. However, the regulation
      of P450c11B3 mRNA expression is different from that of P450c11 beta mRNA, in that
      its abundance is decreased by ACTH in a sex-dependent fashion. Transfection of
      eukaryotic cells with a vector expressing P450c11B3 shows that this form of
      P450c11 can convert 11-deoxycorticosterone (DOC) to corticosterone and thus has
      the same enzymatic activity as P450c11 beta. In addition, P450c11B3 can convert
      DOC to 18-OH DOC and corticosterone to 18-OH corticosterone and thus has 18
      hydroxylase activity similar to P450c11AS, but it lacks detectable 18-oxidase
      activity. Thus, P450c11B3 catalyzes 11 beta- and 18-hydroxylation and thus has a
      spectrum of activities midway between P450c11 beta and P450c11AS.

PMID- 7829498
TI  - Binding of the HIV-1 nucleocapsid protein to the primer tRNA(3Lys), in vitro, is
      essentially not specific.
AB  - The nucleocapsid protein NCp7 of human immunodeficiency virus, type 1, is a key
      component in the viral life cycle. Since, the first common step of all reported
      NCp7 activities corresponds to a nucleic acid-binding step, the NCp7 binding
      parameters to the natural primer tRNA(3Lys) were investigated. Using NCp7
      intrinsic fluorescence, we found that (i) in 0.1 M NaCl, NCp7 bound
      noncooperatively to tRNA(3Lys) with a Kobs = 3.2 x 10(6) M-1 association constant
      and a n = 6 binding site size, (ii) four ionic interactions were formed in the
      NCp7.tRNA(3Lys) complex, and (iii) nonelectrostatic factors provided about 60% of
      the binding energy. These binding parameters were not significantly altered when
      the natural tRNA(3Lys) was replaced by either an in vitro synthetic tRNA(3Lys)
      transcript, the heterologous yeast tRNA(Phe) or the structurally unrelated 5 S
      RNA from Escherichia coli. Moreover, the environment of the intrinsic fluorescent
      reporters (Trp37 and Trp61) was similar in the various complexes. Finally,
      experiments performed at low protein concentration provide no evidence of high
      affinity binding sites. Taken together, our data strongly suggested an
      essentially nonspecific binding of NCp7 to tRNA(3Lys) and thus did not seem to
      support a direct role of NCp7, per se, in the selection of tRNA(3Lys) from the
      pool of cellular tRNAs.

PMID- 7829499
TI  - The delta pH-driven, ATP-independent protein translocation mechanism in the
      chloroplast thylakoid membrane. Kinetics and energetics.
AB  - Previous studies have shown that proteins are transported across the chloroplast
      thylakoid membrane by two very different mechanisms, one of which requires
      stromal factors and ATP, whereas the other mechanism is ATP independent but
      completely reliant on the thylakoidal delta pH. We have examined the role of the
      delta pH in the latter mechanism by simultaneously monitoring the magnitude of
      delta pH (by 9-aminoacridine fluorescence quenching) and the rate of import of
      the 23-kDa photosystem II protein into isolated pea thylakoids. We show that
      protein import can take place, at low but significant rates, at very low values
      of delta pH (in the region of 1.2-1.4), and that plots of the rate of protein
      import against proton concentration gradient are probably hyperbolic in nature.
      There is no evidence for a threshold level of delta pH which is required to drive
      translocation of the 23-kDa protein. Addition of uncouplers midway during import
      incubations results in a rapid and complete inhibition of translocation, showing
      that the continuous presence of the delta pH is required for translocation to
      take place. During import into intact chloroplasts, the intermediate-size 23-kDa
      protein substrate for the thylakoidal protein transport machinery is found only
      in the stromal fraction at all values of delta pH, suggesting that the initial
      interaction with the machinery is relatively weak, reversible and delta pH
      independent. We therefore propose that the delta pH is required for both the
      initiation and completion of translocation; these roles are in marked contrast to
      the roles of protonmotive force in mitochondrial and sec-dependent bacterial
      protein transport.

PMID- 7829500
TI  - A monomeric, tightly folded stromal intermediate on the delta pH-dependent
      thylakoidal protein transport pathway.
AB  - Two distinct mechanisms have been previously identified for the transport of
      proteins across the chloroplast thylakoid membrane, one of which is unusual in
      that neither soluble factors nor ATP are required; the system requires only the
      transthylakoidal delta pH. We have examined this mechanism by studying the
      properties of one of its substrates: the extrinsic 23-kDa protein (23K) of
      photosystem II. Previous work has shown that this protein can be transported into
      isolated thylakoids as the full-length precursor protein; we show that the
      stromal import intermediate form of this protein is similarly translocation
      competent. Gel filtration tests indicate that the stromal intermediate is
      probably monomeric. Protease sensitivity tests on both the initial in vitro
      translation product and the stromal import intermediate show that the presequence
      is highly susceptible to digestion whereas the mature protein is resistant to
      high concentrations of trypsin. The mature protein becomes very sensitive to
      digestion if unfolded in urea, or after heating, and we therefore propose that
      the natural substrate for this translocation system consists of a relatively
      unfolded presequence together with a tightly folded passenger protein. The
      ability of thylakoids to import pre-23K is destroyed by prior treatment of the
      thylakoids with low concentrations of trypsin, demonstrating the involvement of
      surface-exposed proteins in the import process. However, we can find no evidence
      for the binding of pre-23K or i23K to the thylakoid surface, and we therefore
      propose that the initial interaction of these substrates with the thylakoidal
      translocase is weak, reversible, and probably delta pH-independent. In the second
      phase of the translocation mechanism, the delta pH drives either the
      translocation and unfolding of proteins, or the translocation of a fully folded
      protein.

PMID- 7829501
TI  - A G protein is involved in the angiotensin AT2 receptor inhibition of the T-type
      calcium current in non-differentiated NG108-15 cells.
AB  - In non-differentiated NG108-15 cells, both angiotensin II (Ang II) (100 nM) and
      CGP 42112 (100 nM) decreased the T-type calcium current amplitude by 24 +/- 2%
      and 21 +/- 3%, respectively. cGMP is not a mediator of the Ang II effect, since
      loading of cells with 50 microM cGMP did not prevent the inhibitory effects of
      Ang II. The effects of Ang II involves a non-identified GTPase activity since
      incubation with GDP beta S (3 mM) completely reversed the inhibitory effect of
      Ang II while GTP gamma S mimicked its effect. However, Ang II binding was not
      affected by GTP gamma S, and the effect of Ang II was not modified in pertussis
      toxin-treated cells. The inhibitory effect of Ang II on the T-type Ca2+ current
      involves a phosphotyrosine phosphatase activity since sodium orthovanadate
      prevented the effects of Ang II, although microcystin-LR, a selective Ser/Thr
      phosphatase 1 and 2A inhibitor, did not modify the effect of Ang II. These
      results provide the first evidence of a modulation of membrane conductance by Ang
      II through the AT2 receptor and demonstrate the involvement of a phosphotyrosine
      phosphatase and a G protein in the AT2 transduction mechanism in NG108-15 cells.
      Moreover, our data suggest that phosphotyrosine phosphatase activation is
      proximal to receptor occupation, since sodium orthovanadate inhibits both GTPase
      activity and T-type current blockage induced by Ang II or CGP 42112, while GTP
      gamma S inhibition of the T-type calcium current is not impaired.

PMID- 7829502
TI  - Two vitamin D response elements function in the rat 1,25-dihydroxyvitamin D 24
      hydroxylase promoter.
AB  - The interaction between the two vitamin D response elements (DRE) located at -154
      to -134 base pairs (bp) and -262 to -238 bp from the transcription initiation
      site has been studied using reporter gene assays and binding assays by
      electrophoretic gel shift measurements. 3 half-sites separated by 3 bp were found
      necessary for transactivation by the -154 to -125 DRE, while 2 half-sites
      separated by 3 bp were needed for the DRE at -262 to -238 to function. However,
      the two DREs together provided maximal activity. The 93-bp fragment separating
      the two DREs was not required and could be deleted. The most effective binding by
      receptor was found with the two complete DREs (dissociation constant (Kd) = 13.7
      pM), although each DRE bound to the receptor and nuclear accessory factor with
      about 5 nM Kd. The two DREs (a total of 5 half-sites) apparently account for most
      if not all of the transactivation of the rat 24-hydroxylase by 1,25
      dihydroxyvitamin D3. This system represents the most powerful of the DREs
      reported to date.

PMID- 7829503
TI  - Skeletal muscle glucose transport and metabolism are enhanced in transgenic mice
      overexpressing the Glut4 glucose transporter.
AB  - Skeletal muscle glucose transport and metabolism were studied in a line of
      transgenic mice overexpressing the human Glut4 facilitative glucose transporter.
      Skeletal muscle Glut4 protein levels were increased 2-4-fold in transgenic
      animals relative to their nontransgenic litter mates. Glut4 overexpression
      increased total transport activity (measured with 1 mM 2-deoxy-D-glucose) in the
      isolated extensor digitorum brevis muscle in the presence of insulin; this
      increase was due to 1) an increase in basal glucose transport (0.8 +/- 0.1 versus
      0.5 +/- 0.1 mumol.ml-1.20 min-1 in transgenic and control mice, respectively) and
      2) an increase in insulin-stimulated transport (1.5 +/- 0.1 versus 0.8 +/- 0.1
      mumol.ml-1.20 min-1 above basal transport in transgenic and control mice,
      respectively). Glut4 overexpression also increased glucose transport stimulated
      by muscle contractions. In addition, glycolysis and glucose incorporation into
      glycogen were enhanced in muscle isolated from transgenic mice compared to
      controls. These data demonstrate that Glut4 overexpression in skeletal muscle
      increases insulin- and contraction-stimulated glucose transport activity and
      glucose metabolism. These findings are consistent with the role of Glut4 as the
      primary mediator of transport stimulated by insulin or contractions.

PMID- 7829504
TI  - Hormonal and feedback regulation of putrescine and spermidine transport in human
      breast cancer cells.
AB  - The properties and regulation of the mammalian polyamine transport system are
      still poorly understood. In estrogen-responsive ZR-75-1 human breast cancer
      cells, which display low polyamine biosynthetic activity, putrescine and
      spermidine were internalized with high affinity (Km = 3.7 and 0.5 microM,
      respectively) via a single class of saturable transporter shared by both
      substrate types, or via distinct but closely similar carriers. The Vmax, but not
      the Km of polyamine transport was rapidly and synergistically up-regulated by
      estrogens and insulin. The steady decay in transport activity observed in hormone
      deprived cells was accelerated by retinoic acid. The enhancement of uptake
      activity resulting from polyamine depletion was amplified 3-fold by estrogens and
      insulin despite profound growth inhibition, indicating that the cooperative
      hormonal induction of polyamine transport is dissociated from cell growth status.
      Polyamine uptake was under feedback inhibition by at least three distinct
      mechanisms in these cells, namely (i) the induction of a short-lived protein not
      actively synthesized without ongoing uptake or upon polyamine deletion; (ii) a
      more latent, protein synthesis-independent "trans-inhibition" mechanism; and
      (iii) a post-carrier, cycloheximide-sensitive mechanism limiting substrate
      accumulation. The complexity of these multiple levels of feedback transport
      inhibition is in keeping with the cytotoxicity of excessive polyamine content.

PMID- 7829505
TI  - Cloning and subcellular localization of human mitochondrial hsp70.
AB  - We report the cloning, nucleotide sequence, and localization of mitochondrial
      hsp70, a member of the human hsp70 multi-gene family. The human mthsp75 gene was
      cloned by screening an expression library with monoclonal antibody 3A3 that
      recognizes three members of the human hsp70 family (hsp70, hsc70, and a 75-kDa
      protein with characteristics identical to that previously established for
      mitochondrial hsp70). The identity of the 75-kDa protein was confirmed by
      subcellular fraction of HeLa cells and the demonstration that the 3A3-reactive 75
      kDa protein co-fractionates with mitochondrial localized proteins. The nucleotide
      sequence of the respective cDNA clone revealed an open reading frame of 679 amino
      acids with extensive sequence identity with members of the human hsp70 family.
      The derived amino-terminal pre-sequence shares features common to other
      mitochondrial targeting sequences. The identity of the cDNA was unequivocally
      established by introduction of an epitope-tag at the carboxyl terminus of the
      cloned gene, transfection and analysis by immunofluorescence. The tagged 75-kDa
      protein localizes to mitochondria, thus providing conclusive evidence that it
      corresponds to the human mitochondrial hsp70, referred to here as mthsp75.

PMID- 7829506
TI  - Functional aspects of ultra-rapid heme doming in hemoglobin, myoglobin, and the
      myoglobin mutant H93G.
AB  - Heme iron out-of-plane displacement following ligand dissociation in hemoglobin,
      myoglobin, and the proximal cavity mutant H93G is shown to be as rapid as the
      heme iron out-of-plane vibrational period by sub-picosecond time-resolved
      resonance Raman spectroscopy. The results demonstrate that the effect of steric
      repulsion initiated by the spin change of the iron gives rise to heme doming
      independent of covalent attachment of the proximal ligand to the protein. It is
      concluded that the protein plays a passive role in the initial ultrafast heme
      iron motion toward the out-of-plane position observed in the deoxy structure of
      hemoglobin and myoglobin. The results suggest that the spin change of the heme
      iron is the primary cause of rapid heme doming and that steric repulsion of the
      proximal ligand with the heme plays a secondary role in forcing the iron out of
      the heme plane.

PMID- 7829507
TI  - Calcium ion binding to thrombospondin 1.
AB  - We have quantified the binding of Ca2+ to platelet thrombospondin 1 (TSP1) using
      equilibrium dialysis with 45CaCl2. Ca2+ binding to TSP1 was found to be
      cooperative with 10% occupancy at 15-20 microM CaCl2, 90% occupancy at 100 microM
      CaCl2, and a Hill coefficient of 2.4 +/- 0.2 The average apparent Kd was 52 +/- 5
      microM. Maximum binding, assuming Mr = 450,000 and epsilon = 0.918 (A280/mg/ml),
      was 35 +/- 3 Ca2+/TSP1. This value is close to the 33 sites (11 per subunit)
      predicted based on homology of the epidermal growth factor (1 site) and aspartate
      rich (10 sites) regions to known Ca2+ binding sequences. Ca2+ protected the
      aspartate-rich region from trypsin proteolysis, but not until nearly all of the
      Ca2+ binding sites were filled. At lower occupancy of Ca2+ binding sites, several
      limited tryptic digest products were obtained. This finding and the previous
      demonstration of extensive thiol-disulfide isomerization within the aspartate
      rich regions suggest that subregions of the aspartate-rich region are stabilized
      in different conformers. Zn2+, Cu2+, Mn2+, Mg2+, Co2+, Cd2+, and Ba2+ were tested
      for their ability to modulate Ca2+ binding and protease sensitivity of TSP1. Zn2+
      inhibited 40% of the Ca2+ binding but neither protected TSP1 from trypsin
      proteolysis, nor labilized TSP1 toward trypsin proteolysis. These results provide
      direct evidence for high capacity, cooperative and specific binding of Ca2+ to
      conformationally labile aspartate-rich repeats of TSP1.

PMID- 7829508
TI  - Purification of recombinant G proteins from Sf9 cells by hexahistidine tagging of
      associated subunits. Characterization of alpha 12 and inhibition of adenylyl
      cyclase by alpha z.
AB  - A method is described for purification of G protein alpha and beta gamma subunits
      from Sf9 cells infected with recombinant baculoviruses. The subunit to be
      purified is coexpressed with an associated subunit bearing a hexahistidine tag.
      After adsorption of the oligomer to a Ni(2+)-containing column, the subunit to be
      purified is eluted specifically by promoting subunit dissociation with AIF4-. The
      alpha subunits of G12, Gq, Gz, and Gi1 and the beta 1 gamma 2 subunit complex
      were easily and efficiently purified by this method. Results was superior to
      established procedures in all cases. Purified alpha 12 was characterized for the
      first time. The protein has a slow rate of guanine nucleotide exchange (kon, GTP
      gamma S = 0.01 min-1) and a very slow kcat for hydrolysis of GTP (0.1-0.2 min-1).
      GTP gamma S (guanosine 5' -3-O- (thio)triphosphate) alpha 12 does not influence
      the activity of several adenylyl cyclases or phospholipases. Activated alpha z
      inhibits the activity of type I and type V adenylyl cyclases. It is a somewhat
      more potent inhibitor of type V adenylyl cyclase than is activated alpha i1.

PMID- 7829509
TI  - Topological determinants of internal transmembrane segments in P-glycoprotein
      sequences.
AB  - P-glycoprotein (Pgp) is a polytopic membrane protein responsible for multidrug
      resistance in cancer cells. Previously, we have used a coupled cell-free
      translation/translocation system to investigate the membrane orientation of Pgp
      sequences and have made the unexpected observation that predicted transmembrane
      (TM) segments from both the NH2-terminal and COOH-terminal halves inserted in
      microsomal membranes in two different orientations (Zhang, J.-T., Duthie, M., and
      Ling, V. (1993) J. Biol. Chem. 268, 15101-15110). How these topological forms of
      Pgp are regulated is not known. In the present study, we have used site-directed
      mutagenesis to investigate if the amino acids surrounding the internal TM
      segments of Pgp may affect their orientation. We discovered that the charged
      amino acids flanking TM4 are important in determining the membrane orientation of
      the NH2-terminal half molecule of Pgp. This is a novel observation demonstrating
      the existence of internal topogenic sequences in a mammalian polytopic membrane
      protein. These findings thus suggest A) that the topological structure of a
      mammalian polytopic membrane protein does not integrate into the membrane simply
      by following the lead of the first inserted TM segment but that internal TMs may
      have independent topogenic information and B) that the TM segments in a multi
      spanning membrane protein may be more dynamic than have been previously
      anticipated, i.e. mutations in the amino acids surrounding internal TMs could
      drastically change the overall topology of the molecule.

PMID- 7829510
TI  - A COL2A1 mutation in achondrogenesis type II results in the replacement of type
      II collagen by type I and III collagens in cartilage.
AB  - An autosomal dominant mutation in the COL2A1 gene was identified in a fetus with
      achondrogenesis type II. A transition of G2853 to A in exon 41 produced a
      substitution of Gly769 by Ser within the triple helical domain of the alpha 1(II)
      chain of type II collagen, interrupting the mandatory Gly-X-Y triplet sequence
      required for the normal formation of stable triple helical type II collagen
      molecules, resulting in the complete absence of type II collagen in the
      cartilage, which had a gelatinous composition. Type I and III collagens were the
      major species found in cartilage tissue and synthesized by cultured chondrocytes
      along with cartilage type XI collagen. However, cultured chondrocytes produced a
      trace amount of type II collagen, which was retained within the cells and not
      secreted. In situ hybridization of cartilage sections showed that the
      chondrocytes produced both type II and type I collagen mRNA. As a result, it is
      likely that the chondrocytes produced type II collagen molecules, which were then
      degraded. The close proximity of the Gly769 substitution by Ser to the mammalian
      collagenase cleavage site at Gly775-Leu776 may have produced an unstable domain
      that was highly susceptible to proteolysis. The type I and III collagens that
      replaced type II collagen were unable to maintain the normal structure of the
      hyaline cartilage but did support chondrocyte maturation, evidenced by the
      expression of type X collagen in the hypertrophic zone of the growth plate
      cartilage.

PMID- 7829511
TI  - Suppression of human immunodeficiency virus type 1 activity in vitro by
      oligonucleotides which form intramolecular tetrads.
AB  - An oligonucleotide (I100-15) composed of only deoxyguanosine and thymidine was
      able to inhibit human immunodeficiency virus type-1 (HIV-1) in culture assay
      systems. I100-15 did not block virus entry into cells but did reduce viral
      specific transcripts. As assessed by NMR and polyacrylamide gel methods, I100-15
      appears to form a structure in which two stacked guanosine tetrads are connected
      by three two-base long loops. Structure/activity experiments indicated that
      formation of intramolecular guanosine tetrads was necessary to achieve maximum
      antiviral activity. The single deoxyguanosine nucleotide present in each loop was
      found to be extremely important for the overall antiviral activity. The toxicity
      of I100-15 was determined to be well above the 50% effective dose (ED50) in
      culture which yielded a high therapeutic index (> 100). The addition of a
      cholesterol moiety to the 3' terminus of I100-15 (I100-23) reduced the ED50 value
      to less than 50 nM (from 0.12 microM for I100-15) and increased the duration of
      viral suppression to greater than 21 days (versus 7-10 days for I100-15) after
      removal of the drug from infected cell cultures. The favorable therapeutic index
      of such molecules coupled with the prolonged suppression of HIV-1, suggest that
      such compounds further warrant investigation as potential therapeutic agents.

PMID- 7829512
TI  - Effects of apoprotein E on intracellular metabolism of model triglyceride-rich
      particles are distinct from effects on cell particle uptake.
AB  - Apoprotein E (apoE) enhances uptake of triglyceride-rich lipoprotein particles
      (TGRP). We questioned whether apoE would also modulate intracellular metabolism
      of TGRP in addition to its effects on particle uptake. We prepared model TGRP
      with triolein and cholesteryl oleate (1:1, w/w) as the core lipids, emulsified by
      egg yolk phosphatidylcholine, and containing a non-degradable marker,
      [3H]cholesteryl hexadecyl ether. Particles were intermediate density lipoprotein
      sized as determined by core lipid/phospholipid ratios (2.0-3.0/1) and gel
      filtration chromatography on Sepharose CL-2B. Emulsions were incubated with J774
      macrophages for 5 min to 6 h at core lipid concentrations of 300-1200
      micrograms/ml and 0-0.2 microgram recombinant apoE/mg core lipid. Particle uptake
      was determined by [3H]cholesteryl ether uptake and fluorescence microscopy in the
      absence and presence of apoE. Similar uptake of particles with and without apoE
      was achieved by utilizing a 4 times higher particle concentration in the absence
      of apoE. At equivalent levels of uptake, particles with apoE lead to one-half of
      the triglyceride mass accumulation and twice the triglyceride utilization as
      compared to particles without apoE. Further, apoE doubles cell cholesteryl ester
      hydrolysis and to a lesser extent (approximately 30%) increases cholesteryl ester
      resynthesis by acyl-CoA cholesterol acyltransferase. Particles, both with and
      without apoE, reach the lysosomal compartment as determined by colocalization
      with fluorescein-labeled alpha 2-macroglobulin. These results suggest that, in
      addition to its role in enhancing TGRP uptake, apoE has additional effects on
      modulating the cellular metabolism of both triglyceride and cholesteryl ester,
      after particle internalization.

PMID- 7829513
TI  - IgA protease from Neisseria gonorrhoeae inhibits exocytosis in bovine chromaffin
      cells like tetanus toxin.
AB  - When tetanus toxin from Clostridium tetani or IgA protease from Neisseria
      gonorrhoeae is translocated artificially into the cytosol of chromaffin cells,
      both enzymes inhibit calcium-induced exocytosis, which can be measured by changes
      in membrane capacitance. The block of exocytosis caused by both proteases cannot
      be reversed by enforced stimulation with increased calcium concentration. This
      effect differs from the botulinum A neurotoxin-induced block of exocytosis that
      can be overcome by elevation of the intracellular calcium concentration. Tetanus
      toxin is about 50-fold more potent than IgA protease in cells stimulated by
      carbachol. In this case, the release of [3H]noradrenaline was determined. Trypsin
      and endoprotease Glu-C are hardly effective and only at concentrations that
      disturb the integrity of the cells. Like tetanus toxin, IgA protease also splits
      synaptobrevin II, though at a different site of the molecule. However, unlike
      tetanus toxin, it does not cleave cellubrevin. It is concluded that the membranes
      of chromaffin vesicles contain synaptobrevin II, which, as in neurons, appears to
      play a crucial part in exocytosis.

PMID- 7829514
TI  - Rat liver ATP synthase. Relationship of the unique substructure of the F1 moiety
      to its nucleotide binding properties, enzymatic states, and crystalline form.
AB  - The F1 moiety of rat liver ATP synthase has a molecular mass of 370,000, exhibits
      the unique substructure alpha 3 beta 3 gamma delta epsilon, and fully restores
      ATP synthesis to F1-depleted membranes. Here we provide new information about rat
      liver F1 as it relates to the relationship of its unique substructure to its
      nucleotide binding properties, enzymatic states, and crystalline form. Seven
      types of experiments were performed in a comprehensive study. First, the capacity
      of F1 to bind [3H]ADP, the substrate for ATP synthesis and [32P]AMP-PNP (5'
      adenylyl-beta,gamma-imidodiphosphate), a nonhydrolyzable ATP analog, was
      quantified. Second, double-label experiments were performed to establish whether
      ADP and AMP-PNP bind to the same or different sites. Third, total nucleotide
      binding was assessed by the luciferin-luciferase assay. Fourth, F1 was
      subfractionated into an alpha gamma and a beta delta epsilon fraction, both of
      which were subjected to nucleotide binding assays. Fifth, the nucleotide binding
      capacity of F1 was quantified after undergoing ATP hydrolysis. Sixth, the
      intensity of the fluorescence probe pyrene maleimide bound at alpha subunits was
      monitored before and after F1 experienced ATP hydrolysis. Finally, the catalytic
      activity and nucleotide content of F1 obtained from crystals being used in x-ray
      crystallographic studies was determined. The picture of rat liver F1 that emerges
      is one of an enzyme molecule that 1) loads nucleotide readily at five sites; 2)
      requires for catalysis both the alpha gamma and the beta delta epsilon fractions;
      3) directs the reversible binding of ATP and ADP to different regions of the
      enzyme's substructure; 4) induces inhibition of ATP hydrolysis only after ADP
      fills at least five sites; and 5) exists in several distinct forms, one an
      active, symmetrical form, obtained in the presence of ATP and high P(i) and on
      which an x-ray map at 3.6 A has been reported (Bianchet, M., Ysern, X., Hullihen,
      J., Pedersen, P. L., and Amzel, L. M. (1991) J. Biol. Chem. 266, 21197-21201).
      These results are discussed within the context of a multistate model for rat
      liver F1 and also discussed relative to those reported for bovine heart F1, which
      has been crystallized with inhibitors in an asymmetrical form and has a
      propensity for binding nucleotides more tightly.

PMID- 7829515
TI  - A long purine-pyrimidine homopolymer acts as a transcriptional diode.
AB  - Polypurine-polypyrimidine (R.Y) sequences have the unusual ability to form DNA
      triple helices. Such tracts are overrepresented upstream of eukaryotic genes,
      although a function there has not been clear. We report that transcription in
      vitro into one such upstream R.Y tract in the direction that makes a
      predominantly purine RNA is effectively blocked by formation of an intramolecular
      triple helix. The triplex is triggered by transcription and stabilized by the
      binding of nascent purine RNA to the template. Transcription in the opposite
      direction is not restricted. Polypurine-polypyrimidine DNA may provide a dynamic
      and selective block to transcription without the aid of accessory proteins.

PMID- 7829516
TI  - Primary structure and developmental expression of Fbn-1, the mouse fibrillin
      gene.
AB  - Previous studies have reported > 10 kilobases of human fibrillin-1 cDNA sequence,
      but a consensus regarding the 5' end of the transcript remains to be worked out.
      One approach to developing a clear consensus would be to search for regions of
      evolutionary conservation in transcripts from a related species such as mouse. As
      reported here, the mouse fibrillin-1 transcript encodes a highly conserved
      polypeptide of 2,871 amino acids. The upstream sequence that flanks the ATG is
      considerably less well conserved, however. Indeed, the ATG codon (which occurs in
      the context of a Kozak consensus sequence and is located just upstream of a
      consensus signal peptide) signals the point where human and mouse fibrillin-1
      sequences cease to be nearly identical. Together, these results are consistent
      with previous efforts by Pereira et al. (Pereira, L., D'Alessio, M., Ramirez, F.,
      Lynch, J. R., Sykes, B., Pangilinan, T., and Bonadio, J. (1993) Human Mol. Genet.
      2, 961-968) to identify the human fibrillin-1 translational start site. Sequences
      immediately upstream of the ATG are GC-rich and devoid of TATA and CCAAT boxes,
      which suggests that the mouse fibrillin-1 gene will be broadly expressed. A
      survey of expression in mouse embryo tissues is consistent with this hypothesis
      and suggests two novel functions for fibrillin-associated microfibrils in non
      elastic connective tissues.

PMID- 7829517
TI  - Identification, purification, and characterization of cell-surface retention
      sequence-binding proteins from human SK-Hep cells and bovine liver plasma
      membranes.
AB  - Cell-surface retention is a newly identified mechanism associated with the
      secretion of certain polypeptide growth factors and cytokines. This novel form of
      secretion appears to be mediated by cell-surface retention sequences (CRS) in the
      polypeptide molecules. To test the hypothesis that high-affinity CRS-binding
      proteins (CRS-BPs) are responsible for the cell-surface retention, we identified
      and characterized the high-affinity binding sites on various cell types for 125I
      labeled CRS peptide (sis) and CRS peptide (VEGF), each of which contained the
      putative CRS motifs of platelet-derived growth factor B (c-sis) and vascular
      endothelial cell growth factor, respectively. Scatchard plot analysis revealed a
      single class of high-affinity binding sites with Kd = 0.5-0.7 nM and
      approximately 22,000-55,000 sites/cell. High-affinity binding activity could be
      demonstrated between pH 4.5 and 8.0, but was much greater below 6.0 (maximum pH
      5.0-5.5). The ligand binding activity was inhibited by heparin, polylysine, and
      protamine, but not by cytochrome c. CRS-BPs responsible for the high-affinity
      binding were identified as 60-72-kDa proteins by ligand affinity labeling. CRS
      BPs were purified from human SK-Hep cells and bovine liver plasma membranes by
      Triton X-100 extraction followed by affinity column chromatography on wheat germ
      lectin-Sepharose 4B and CRS peptide (sis)-Affi-Gel 10. Purified CRS-BPs exhibited
      ligand binding properties (pH profile and inhibitor sensitivity) similar to those
      of the high-affinity binding sites for CRS peptides on cultured cells. The major
      CRS-BPs (p60, p66, and p72) purified from bovine liver plasma membranes were
      found to have identical N-terminal amino acid sequence and were assumed to
      represent different forms of the same gene product, which we have designated CRS
      BP1.

PMID- 7829518
TI  - Alternative splicing of ED-A and ED-B sequences of fibronectin pre-mRNA differs
      in chondrocytes from different cartilaginous tissues and can be modulated by
      biological factors.
AB  - The alternative splicing of the ED-A and ED-B segments of fibronectin pre-mRNA
      was examined in epiphyseal, costal, and meniscal cartilage from 3-week-old
      beagles and in nasal, tracheal, articular, and meniscal cartilage from 1- and 2
      year-old Labrador retrievers. In contrast to the 100% expression of ED-B(+) mRNA
      that has been reported for embryonic chick cartilage (Bennett, V.D., Pallante,
      K.M., and Adams, S.K. (1991) J. Biol. Chem. 266, 5918-5924), all cartilages
      studied expressed both the ED-B(+) and ED-B(-) forms of fibronectin mRNA with the
      exception of the trachea, in which expression was 100% ED-B(-). Of all cartilages
      studied, only the meniscus had detectable levels of ED-A(+) mRNA. Placing
      articular cartilage chondrocytes in primary monolayer culture dramatically up
      regulated the expression of ED-A(+) mRNA to 25% of the total, and this expression
      was further increased by the addition of transforming growth factor beta 1 or
      fucoidan to the culture medium. The expression of ED-B(+) mRNA remained at about
      18% in the cultured chondrocytes and was not further affected by either
      transforming growth factor beta 1 or fucoidan. In contrast, dibutyryl cyclic
      adenosine monophosphate decreased the relative expression of both the ED-A(+) and
      ED-B(+) forms of fibronectin pre-mRNA. We concluded that the expression of ED
      B(+) fibronectin remains relatively high in chondrocytes from cartilaginous
      canine tissues (15-35%) with the exception of the trachea, in contrast to the
      less than 10% expression of ED-B(+) fibronectin reported for other non-fetal
      tissues.

PMID- 7829519
TI  - Analysis of a mouse gene encoding three steps of purine synthesis reveals use of
      an intronic polyadenylation signal without alternative exon usage.
AB  - A single mouse genomic locus encodes proteins catalyzing three steps of purine
      synthesis, glycinamide ribonucleotide synthetase (GARS), aminoimidazole
      ribonucleotide synthetase (AIRS), and glycinamide ribonucleotide
      formyltransferase (GART). This gene has 22 exons and spans 28 kilobases. The
      existence of a second genetic locus and closely related pseudogenes was ruled out
      by Southern analysis. Mouse tissues express two related classes of messages
      encoded by this single locus: a trifunctional GARS-AIRS-GART mRNA and a
      monofunctional GARS mRNA. These transcripts used the same set of multiple
      transcriptional start sites, and both used the same first 10 exons. CCAAT and
      TATA elements were not found for this locus. Exon 11, which represented the last
      coding sequence of the GARS domain, was differentially utilized for the two
      messages. The trifunctional mRNA was generated by splicing exon 11 to exon 12,
      the first coding sequence for the AIRS domain with subsequent use of a
      polyadenylation signal at the end of exon 22. Genomic sequence corresponding to
      the 3'-UTR of the monofunctional GARS mRNA was contiguous with exon 11, so that
      the smaller message arose from the recognition of one of the multiple
      polyadenylation signals present within the intron between exons 11 and 12. Hence,
      polyadenylation of the primary transcript at a position corresponding to an
      intron of the genomic locus was responsible for the generation of the
      monofunctional GARS class of mRNAs. This utilization of an intronic
      polyadenylation site without alternative exon usage is comparable to the
      mechanism whereby both secreted and membrane-bound forms of the immunoglobulin mu
      heavy chain are made from a single genetic locus.

PMID- 7829520
TI  - cDNA cloning of MCT2, a second monocarboxylate transporter expressed in different
      cells than MCT1.
AB  - Low stringency screening of a cDNA library from hamster liver yielded a cDNA
      encoding MCT2, a monocarboxylate transporter that is 60% identical to hamster
      MCT1, the first monocarboxylate transporter to be isolated. The functional
      properties of the two MCTs were compared by expression in Sf9 insect cells using
      recombinant baculovirus vectors. Like MCT1, MCT2 transported pyruvate and
      lactate. The two transporters were sensitive to inhibition by phloretin and by
      alpha-cyano-4-hydroxycinnamate. MCT1, but not MCT2, was sensitive to
      organomercurial thiol reagents such as p-chloromercuribenzoic acid.
      Immunoblotting and immunofluorescence studies revealed a strikingly different
      tissue distribution of the two MCTs. MCT1 was present in erythrocytes and on the
      basolateral surfaces of intestinal epithelial cells. MCT2 was not detectable in
      these tissues, but it was abundant on the surface of hepatocytes. In the stomach,
      MCT1 was present on the basolateral surfaces of epithelial cells; in contrast,
      MCT2 was expressed on parietal cells of the oxyntic gland. In the kidney, MCT1
      was present on the basolateral surfaces of epithelial cells in proximal tubules,
      whereas MCT2 was restricted to the collecting ducts. MCT1 was expressed on sperm
      heads in the testis and proximal epididymis. In the distal epididymis, it
      disappeared from sperm and appeared on the microvillar surface of the lining
      epithelium. In contrast, MCT2 was present on sperm tails throughout the
      epididymis and not on the epithelium. Both transporters were expressed in
      mitochondria-rich (oxidative) skeletal muscle fibers and cardiac myocytes. These
      findings suggest that MCT1 and MCT2 are adapted to play different roles in
      monocarboxylate transport in different cells of the body.

PMID- 7829521
TI  - Developmental changes of the 26 S proteasome in abdominal intersegmental muscles
      of Manduca sexta during programmed cell death.
AB  - cDNA clone MS73 codes for an ATPase that is a regulatory subunit of the 26 S
      proteasome. Reverse transcriptase polymerase chain reaction analysis demonstrates
      that the expression of the gene dramatically increases in the pre-eclosion
      period. Western analyses show increases in other related. ATPases including MS73,
      MSS1, and mts2 but not TBP1. A similar increase in the 30-kDa subunit of the 20 S
      proteasome occurs. There are accompanying large changes in the peptidase
      activities of the 26 S proteasome. Relative to the 30-kDa subunit, there is no
      change in MSS1 and MS73, a 3-fold increase in mts2, and a 5-fold decline in TBP1.
      A large increase in the concentration of 26 S proteasomes together with extensive
      regulatory reprogramming may facilitate rapid muscular proteolysis.

PMID- 7829522
TI  - Cloning and sequence analysis of the human mitochondrial translational initiation
      factor 2 cDNA.
AB  - Complete cDNAs encoding human mitochondrial translational initiation factor 2 (IF
      2mt) have been obtained from liver, heart, and fetal brain cDNA libraries. These
      cDNAs have a long open reading frame 2181 residues in length encoding a protein
      of 727 amino acids. Overall, human IF-2mt has 30-40% identity to the
      corresponding prokaryotic factors. Surprisingly, it is no more homologous to
      yeast IF-2mt than to the IF-2s from bacterial sources. The greatest region of
      conservation lies in the G-domain of this factor with less conservation in the
      COOH-terminal half of the protein and very little homology near the amino
      terminus. The 5'-untranslated leaders of the liver and heart cDNAs contain a
      number of short open reading frames. These sequences may play a role in the
      translational activity of the IF-2mt mRNA. Northern analysis indicates that the
      IF-2mt gene is expressed in all tissues but that the level of expression varies
      over a wide range.

PMID- 7829523
TI  - Promoter elements of the mouse acetylcholinesterase gene. Transcriptional
      regulation during muscle differentiation.
AB  - The increase in acetylcholinesterase expression during muscle differentiation
      from myoblasts to myotubes was shown previously to reflect primarily a greater
      stability of the messenger RNA (mRNA). Here, we investigate the regulation of the
      acetylcholinesterase gene during early determination of the muscle phenotype. (i)
      We employ myogenic transcription factors to transform non-muscle cells into
      myoblasts in order to assess the role of the myogenic transcription factors in
      this regulation. (ii) We analyze the Ache promoter region by deletion analysis,
      point mutagenesis, and gel mobility shift assays. The myogenic transcription
      factors do not accelerate transcription of the Ache gene in spite of the presence
      of E-boxes at -335 base pairs from the start of transcription and in the first
      intron, and they are not able to trigger stabilization of the Ache mRNA when
      constitutively expressed in 10T1/2 fibroblasts. A GC-rich region (at -105 to -59
      base pairs from the start of transcription) containing overlapping binding sites
      for the transcription factors Sp1 and Egr-1 is essential for promoter activity.
      Mutation of the Sp1 sites dramatically reduces the promoter activity while
      mutation of the Egr-1 sites has little effect. Sp1 and Egr-1 compete for binding
      to overlapping sites and an increase in Egr-1 decreases the expression of the
      Ache gene.

PMID- 7829524
TI  - Identification by in vitro mutagenesis of the interaction of two segments of
      C2MstC1, a chimera of cytochromes P450 2C2 and P450 2C1.
AB  - A hybrid cytochrome P450, C2MstC1, with 306 N-terminal amino acids derived from
      cytochrome P450 2C2 sequence and 184 C-terminal amino acids from cytochrome P450
      2C1 acquires a novel progesterone 21-hydroxylase activity which is absent in the
      parent enzymes. Extension of the cytochrome P450 2C2 sequence to residue 382
      reduced progesterone hydroxylase activity to 5% of that of C2MstC1, while further
      extension to residue 411 or 462 increased activity back to about 30 or 40%,
      respectively. In the chimera with cytochrome P450 2C2 sequence to residue 382,
      substitution of cytochrome P450 2C1 amino acids at positions 368, 369, and 374
      increased progesterone hydroxylase activity to a level equivalent to that of
      C2MstC1. In the chimera with cytochrome P450 2C2 sequence extending to residue
      411, substitutions of P450 2C1 amino acids at positions 386 and 388, in addition
      those at 368, 369, and 374, were required to obtain activities equivalent to that
      of C2MstC1, which suggests an interaction between these two regions. The lauric
      acid hydroxylase activities of all chimeras and mutant cytochromes P450 differed
      by 2-fold or less, demonstrating that the changes in progesterone hydroxylase
      activity reflected altered interactions with the substrate. Alignment of
      cytochrome P450 2C1 sequence with cytochromes P450cam, P450BM-3, and P450terp
      predicts that residues 368/369 and 386/388 are in adjacent antiparallel strands
      of the same beta-sheet, in agreement with the experimental data suggesting an
      interaction between these two regions.

PMID- 7829525
TI  - Characterization of the endogenous insulin receptor-related receptor in
      neuroblastomas.
AB  - A gene encoding a putative third member of the insulin receptor family (called
      the insulin receptor-related receptor or IRR) was isolated in 1989. However, the
      naturally occurring protein product encoded by this gene has yet to be described.
      In the present studies, we have generated four monoclonal antibodies to a
      recombinantly expressed chimera, which contains the extracellular domain of human
      IRR. These antibodies were found to specifically recognize the chimeric IRR (and
      not the insulin or insulin-like growth factor I receptors), and two of the
      antibodies were capable of acting as partial agonists in the cells expressing the
      chimeric IRR. These antibodies have therefore been utilized to study the
      expression and properties of the native receptor. In contrast to the two other
      members of this receptor family, the endogenous IRR protein had only a very
      limited expression, being detected only in neuroblastomas. In primary
      neuroblastomas, the levels of the receptor were highest in samples from stage A
      tumors (those which are generally more highly differentiated and have higher
      levels of the nerve growth factor receptor). The endogenous IRR could also be
      detected in a neuroblastoma cell line (called IMR-5 cells). In these cells, IRR
      could be shown to be partly present as a hybrid with the insulin and insulin-like
      growth factor-I receptors but not with the receptor for nerve growth factor. The
      intrinsic tyrosine kinase activity of this endogenous IRR was activated by the
      agonist monoclonal antibody to IRR but not by nerve growth factor, insulin-like
      growth factor I, or insulin. Finally, this monoclonal antibody was found to
      stimulate mitogen-activated protein kinase activity in these cells. In summary,
      these studies demonstrate for the first time that the IRR protein is normally
      expressed, that its levels are highest in neuronal tissues, and that it can form
      hybrid receptors with the two other members of this receptor family but not with
      the more distantly related nerve growth factor receptor.

PMID- 7829526
TI  - A 19-kDa protein belonging to a new family is expressed in the Golgi apparatus of
      neural cells.
AB  - The mouse 8.5 mRNA encodes a 171-residue novel protein which displays a highly
      significant similarity with the product of the previously characterized neuronal
      p1A75 cDNA (Sutcliffe, J.G., Milner, R.J., Shinnick, T.M., and Bloom, F.E. (1983)
      Cell 33, 671-682). Northern blot and in situ hybridization experiments indicated
      that the 8.5 mRNA is specifically expressed in neural and neuroendocrine tissues.
      An affinity-purified antibody directed against the recombinant 8.5 protein
      demonstrated the existence of the 19-kDa natural protein in brain and evidenced
      its prominent juxtanuclear Golgi-like localization in cultured neurons.
      Ultrastructural analysis of the same preparation revealed a specific labeling of
      all the Golgi saccules and of some vesicles in the Golgi zone. In transfected COS
      cells, the exogenous protein was also detected in the Golgi area, indicating,
      therefore, the presence of a Golgi targeting signal in its primary sequence.

PMID- 7829527
TI  - Wild type p53 stimulates expression from the human multidrug resistance promoter
      in a p53-negative cell line.
AB  - The effect of human wild type and mutant p53 proteins on the human multidrug
      resistance (MDR1) promoter was studied in a p53-negative human cell line.
      Transient expression of MDR1 promoter-chloramphenicol acetyltransferase reporter
      gene constructs (MDRCAT) cotransfected with p53 expression vectors was analyzed
      in H358 lung carcinoma cells. Cotransfection with a wild type p53 expression
      vector stimulated MDRCAT activity, while cotransfection with mutant p53
      expression vectors altered at amino acid positions 181, 252, 258, or 273 failed
      to stimulate expression. Wild type p53 stimulation of MDRCAT activity was time
      dependent with maximal expression occurring 24-30 h following transfection and
      correlating with high p53 protein levels. MDR1 promoter deletion analysis
      suggested that the sequences involved in wild type p53 stimulation of MDRCAT
      activity were contained within the region from -39 to +53 relative to the start
      of transcription at +1. This region contains no TATA or p53 consensus binding
      sequence but does contain an initiator sequence. Wild type p53 stimulation of
      MDRCAT expression also occurred in parental and doxorubicin-resistant SW620 colon
      and parental 2780 ovarian cancer cell lines, indicating that wild type p53
      mediated simulation of the MDR1 promoter is not restricted to a single cell line.

PMID- 7829528
TI  - Isoalloxazine ring of FAD is required for the formation of the core in the Hsp60
      assisted folding of medium chain acyl-CoA dehydrogenase subunit into the assembly
      competent conformation in mitochondria.
AB  - We studied the role of FAD in the intramitochondrial folding and assembly of
      medium-chain acyl-CoA dehydrogenase (MCAD), a homotetrameric mitochondrial enzyme
      containing a molecule of non-covalently bound FAD/monomer. In the MCAD molecule,
      FAD is buried in a crevice containing the active center. We have previously shown
      that upon import into mitochondria, newly processed MCAD is first incorporated
      into a high molecular weight (hMr) complex and that the hMr complex mainly
      consisted of MCAD-heat-shock protein 60 (hsp60) complex (Saijo, T., Welch, W.J.,
      and Tanaka, K (1994) J. Biol. Chem. 269, 4401-4408). In the present study, we
      incubated in vitro synthesized precursor MCAD with mitochondria isolated from
      normal and riboflavin-deficient rat liver for 10-60 min and fractionated the
      solubilized mitochondria using gel filtration. The amount of MCAD in the hMr
      complex was larger and that of tetramer was smaller in riboflavin-deficient
      mitochondria than in control at any time point. In addition, riboflavin-deficient
      mitochondria were solubilized after 10-min import in a buffer containing ATP and
      were chased in the presence of FAD, FMN, or NAD+ or without any addition. The
      mitochondrial proteins were analyzed using gel filtration or immunoprecipitated
      with anti-hsp60 antibody. After 60-min chase in the presence of FAD, the majority
      of MCAD in the complex with hsp60 was transferred to tetramer, whereas no such
      transfer occurred after the chase in the absence of FAD. When chase was done in
      the presence of FMN, a significant amount of MCAD was transferred from the
      complex with hsp60 to tetramer, but the transfer was not as efficient as in the
      presence of FAD. The chase in the presence of NAD+ resulted in no transfer. These
      data suggest that isoalloxazine ring of FAD plays a critical role, exerting
      nucleating effect, in the hsp60-assisted folding of MCAD subunit into an assembly
      competent conformation, probably assisting the formation of the core.

PMID- 7829529
TI  - A yeast type II topoisomerase selected for resistance to quinolones. Mutation of
      histidine 1012 to tyrosine confers resistance to nonintercalative drugs but
      hypersensitivity to ellipticine.
AB  - A mutant yeast type II topoisomerase was generated by in vitro mutagenesis
      followed by selection in vivo for resistance to the quinolone CP-115,953. The
      resulting mutant enzyme had a single point mutation which converted His1012 to
      Tyr (top2H1012Y). top2H1012Y was overexpressed in yeast, purified, and
      characterized in vitro. The mutant type II topoisomerase was slightly less active
      than the wild type enzyme, apparently due to a decreased affinity for DNA. The
      affinity of the mutant enzyme for ATP was similar to that of wild type
      topoisomerase II. As determined by DNA cleavage assays, top2H1012Y was resistant
      to CP-115,953 and etoposide both prior to and following the DNA strand-passage
      event. In marked contrast, the mutant enzyme displayed wild type sensitivity to
      amsacrine and was severalfold hypersensitive to ellipticine. A similar pattern of
      resistance was observed in yeast cells harboring the top2H1012Y allele. Thus, it
      appears that the mutant type II topoisomerase can distinguish between
      nonintercalative and intercalative agents. Finally, the His1012-->Tyr mutation
      defines a potential new drug resistance-conferring region on eukaryotic
      topoisomerase II.

PMID- 7829530
TI  - Identification of Rlk, a novel protein tyrosine kinase with predominant
      expression in the T cell lineage.
AB  - The control of phosphorylation by protein tyrosine kinases represents an
      important regulatory mechanism in T cell growth, function, and differentiation.
      We have identified a 62-kDa murine protein tyrosine kinase predominantly
      expressed within the T cell lineage, which we have termed Rlk (for Resting
      lymphocyte kinase). rlk mRNA was found to be expressed in the fetal thymus as
      early as day 13 of embryonic development as well as in adult thymus and mature
      resting peripheral T cells. The sequence of rlk showed that it is most closely
      related to the subfamily of cytoplasmic tyrosine kinases that includes the Btk,
      Itk, and Tec proteins. However, Rlk differs from these kinases by virtue of its
      unique aminoterminal domain, which lacks a region of pleckstrin homology common
      to the other members of this protein subfamily. Examination of rlk abundance
      within different T cell subpopulations revealed preferential expression in Th1
      relative to Th2 T cell clones, suggesting a possible role in signal transduction
      pathways that selectively regulate cytokine production in mature CD4+ T cell
      subsets. Rlk thus represents a novel cytoplasmic tyrosine kinase with potential
      functions in intrathymic T cell development and mature T cell signaling.

PMID- 7829531
TI  - Mutagenesis of the regulatory subunit (RII beta) of cAMP-dependent protein kinase
      II beta reveals hydrophobic amino acids that are essential for RII beta
      dimerization and/or anchoring RII beta to the cytoskeleton.
AB  - In neurons cAMP-dependent protein kinase II beta (PKAII beta) is sequestered in
      the dendritic cytoskeleton because the regulatory subunit (RII beta) of the
      enzyme is tightly bound by A Kinase Anchor Proteins (AKAPs). The prototypic
      neuronal anchor protein AKAP75 has a COOH-terminal 22-residue RII beta binding
      (tethering) site. A key feature of the tethering site is that several amino acids
      with large aliphatic side chains mediate the high-affinity binding of RII beta.
      Mutagenesis, recombinant protein expression, and physicochemical characterization
      were used to investigate the structural basis for the homodimerization and AKAP75
      binding activities of RII beta. Several crucial residues are located in an NH2
      terminal region that encompasses amino acids 13-36. Substitution of Ala for Leu13
      or Phe36 generates monomeric RII beta subunits that cannot bind AKAP75. The
      results are not due to general misfolding since mutant RII beta monomers bind
      cAMP and inhibit the catalytic subunit of PKAII beta with the same affinity and
      efficacy as wild-type RII beta dimers. Moreover, substitution of Ala for Leu12,
      Val20, Leu21, Phe31, Leu33, or Leu39 and replacement of Leu13 with Ile or Val did
      not impair the dimerization reaction. Evidently, large hydrophobic side chains of
      Leu13 and Phe36 play pivotal roles in stabilizing RII beta-RII beta interactions.
      A secondary consequence of destabilizing RII beta dimers is the loss of
      intracellular targeting/anchoring capacity because monomers fail to bind AKAP75.
      Other NH2-terminal residues directly modulate the affinity of RII beta dimers for
      the AKAP75 tethering site. Replacement of Val20-Leu21 with Ala-Ala produced a
      dimeric RII beta protein that binds AKAP75 approximately 4% as avidly as wild
      type RII beta. It is possible that the aliphatic side chains of Val20 and Leu21
      interact with the essential Leu and Ile residues in the AKAP75 tethering region.

PMID- 7829532
TI  - Deoxynucleoside triphosphate and pyrophosphate binding sites in the catalytically
      competent ternary complex for the polymerase reaction catalyzed by DNA polymerase
      I (Klenow fragment).
AB  - We have employed site-directed mutagenesis to identify those amino acid residues
      that interact with the deoxynucleoside triphosphate (dNTP) and pyrophosphate in
      the Klenow fragment-DNA-dNTP ternary complex. Earlier structural, mutagenesis,
      and labeling studies have suggested that the incoming dNTP molecule contacts a
      region on one side of the polymerase cleft, primarily involving residues within
      the so-called "fingers" subdomain. We have made mutations in residues seen to be
      close to the dNTP in the crystal structure of the Klenow fragment-dNTP binary
      complex and have examined their kinetic parameters, particularly Km(dNTP). The
      results are consistent with the notion that there are significant differences
      between the dNTP interactions in the binary and ternary complexes, although some
      contacts may be present in both. When dTTP is the incoming nucleotide, the side
      chains of Arg754 and Phe762 make the largest contributions to binding;
      measurement of Km(PPi) suggests that Arg754 contacts the beta- or gamma-phosphate
      of the dNTP. With dGTP, the contribution of Arg754 remains the same, but the
      additional interactions are provided by both Lys758 and Phe762, suggesting that
      the binding of the incoming dNTP is not identical under all circumstances.
      Mutations in Arg754 and Lys758 also cause a substantial decrease in the rate of
      polymerase-catalyzed incorporation, and sulfur elemental effect measurements
      indicate that loss of Arg754 (and perhaps also Lys758) slows the rate of the
      chemical step of the reaction. Mutations of Arg682, His734, and Tyr766 affect the
      binding of DNA, suggesting that these mutations, whose effect on dNTP binding is
      small, may influence dNTP binding indirectly via the positioning of the DNA
      template-primer.

PMID- 7829533
TI  - Role of erythroid Kruppel-like factor in human gamma- to beta-globin gene
      switching.
AB  - Erythroid Kruppel-like factor (EKLF) is an erythroid-specific transcription
      factor that contains zinc finger domains similar to the Kruppel protein of
      Drosophila melanogaster. Previous studies demonstrated that EKLF binds to the
      CACCC box in the human beta-globin gene promoter and activates transcription.
      CACCC box mutations that cause severe beta-thalassemias in humans inhibit EKLF
      binding. Results described in this paper suggest that EKLF functions
      predominately in adult erythroid tissue. The EKLF gene is expressed at a 3-fold
      higher level in adult erythroid tissue than in fetal erythroid tissue, and the
      EKLF protein binds to the human beta-globin promoter 8-fold more efficiently than
      to the human gamma-globin promoter. Co-transfection experiments in the human
      fetal-like erythroleukemia cell line K562 demonstrate that over-expression of
      EKLF activates a beta-globin reporter construct 1000-fold; a linked gamma-globin
      reporter is activated only 3-fold. Mutation of the beta-globin CACCC box severely
      inhibits activation. These results demonstrate that EKLF is a developmental stage
      enriched protein that preferentially activates human beta-globin gene expression.
      The data strongly suggest that EKLF is an important factor involved in human
      gamma- to beta-globin gene switching.

PMID- 7829534
TI  - Post-transcriptional regulation of the stanniocalcin gene by calcium.
AB  - Stanniocalcin (STC) is a Ca(2+)-regulating hormone produced by the corpuscles of
      Stannius in bony fish. Calcium has been shown to stimulate STC synthesis at
      multiple levels including the level of gene expression. The purpose of this study
      was to determine the effects of Ca2+ on STC mRNA stability. The half-life of STC
      mRNA was measured in primary cultured trout corpuscles of Stannius cells
      maintained in either normal (1.2 mM) or high (1.9 mM) levels of extracellular
      calcium and treated with the transcriptional inhibitor alpha-amanitin. In cells
      maintained in 1.2 mM Ca2+, STC mRNA levels decreased progressively over time with
      an estimated half-life of approximately 71 h. However, message levels remained
      unchanged for up to 4 days in cells maintained in 1.9 mM Ca2+, indicating that
      the transcript had been stabilized in response to Ca2+ stimulation. Blocking
      transcription prior to exposing cells to high Ca2+ did not alter the stabilizing
      effects of the cation, indicating that synthesis and processing of the mRNA
      transcript were not involved in message stabilization. Inhibiting protein
      synthesis with cycloheximide also had no influence on the stabilizing effects of
      high calcium. The experiments involving cycloheximide further suggested that the
      mechanism of mRNA stabilization involved protein-nucleic acid interactions in the
      cytoplasm, whereby the polysomal complex protected the mRNA from degradation.
      These data demonstrate that the stimulatory effect of Ca2+ on STC gene expression
      is due, in part, to mRNA stabilization.

PMID- 7829535
TI  - Major histocompatibility-encoded human proteasome LMP2. Genomic organization and
      a new form of mRNA.
AB  - LMP2 is one of the two proteasome subunits encoded by genes in the major
      histocompatibility complex class II region. Here we report the genomic
      organization of human LMP2 gene. Sequence analysis of polymerase chain reaction
      amplified cDNA from a number of lymphoblastoid cell lines demonstrated two forms
      of LMP2 mRNA, one (LMP2.1) complete and homologous to the published LMP2 genomic
      sequence from cosmid clones, and the other (LMP2.s) a smaller transcript
      resulting from splicing of a 30-base pair fragment from the first exon.
      Antibodies to recombinant LMP2.s protein (22.3 kDa) were raised in rabbits. This
      anti-LMP2.s serum recognized both recombinant proteins (LMP2.1 = 23.3 kDa and
      LMP2.s = 22.3 kDa) and a single protein of 21.5 kDa molecular mass in lysates
      from human lymphoblastoid cell lines. Pulse-chase experiments demonstrated that
      LMP2 polypeptide also undergoes processing from 22.3- to 21.5-kDa protein when
      incorporated into proteasomes. These data suggest that the processing of human
      LMP2 subunit takes place both at the transcription and post-translational levels.
      Northern blot analysis showed that the LMP2 mRNA is expressed in lymphoblastoid
      cell lines and in fibroblasts following gamma-interferon induction, but not in
      brain, smooth muscle, fibroblasts (uninduced), and colon epithelial cells.

PMID- 7829536
TI  - Urinary dopamine and noradrenaline outputs during large acute changes in oral
      salt intake in healthy Chinese subjects.
AB  - 1. In order to investigate the role of renal dopamine and sympathetic activity in
      the natriuretic response to oral sodium loading in Chinese subjects, we studied
      the effects of two different sodium intakes (20 followed by 220 mmol day-1 each
      given for 5 days) on mean arterial pressure (MAP) and the urinary excretion of
      sodium, dopamine (DA) and noradrenaline (NA) in eight healthy subjects. 2. MAP
      did not change. There was an eight- to ninefold increase in sodium excretion (P <
      0.01). An 8-17% increase in urinary DA (P < 0.05) over the first 3 days, and a
      22% decrease in urine NA (P < 0.05) on the last day of the high sodium intake
      were seen. 3. The relatively small increase in urinary DA, despite an eleven-fold
      increase in sodium intake from a state of marked sodium deprivation, may suggest
      that, in healthy Chinese subjects, the renal DA mechanism only contributes partly
      to the acute natriuretic response. Furthermore, the renal DA response appeared to
      be attenuated during the period of high sodium intake. 4. There is no evidence
      from the present study that a reduction in sympathetic activity plays an
      important role in the acute natriuretic response to sodium loading in this group
      of subjects.

PMID- 7829537
TI  - Release of endogenous ATP from the vasa deferentia of the rat and guinea-pig by
      the indirect sympathomimetic tyramine.
AB  - 1. Adenosine 5'triphosphate (ATP) as well as [3H]-noradrenaline ([3H]-NA) is
      released by perfusion of the vas deferens with the indirect sympathomimetic
      tyramine (100 microM); this result is consistent with the concept of sympathetic
      cotransmission. 2. While tyramine produced a strong contraction in the vas
      deferens of the rat, it had little mechanical action in the guinea-pig vas
      deferens. This appears to be largely because tyramine induces considerably lower
      levels of release of both ATP and NA from the guinea-pig vas deferens compared to
      that of the rat. Furthermore, NA released by tyramine appears to release ATP from
      a secondary pool in the rat vans deferens, but not that of the guinea-pig, since
      prazosin reduced the tyramine-induced release of ATP in the rat vas deferens. 3.
      alpha,beta-Methylene ATP (alpha,beta-meATP) increased both the spontaneous
      release of ATP and the tyramine-evoked efflux of ATP and [3H]-NA. The basal and
      tyramine-induced efflux of [3H]-NA was also enhanced by the alpha 1-adrenoceptor
      antagonist, prazosin, suggesting that prejunctional alpha 1-adrenoceptors may
      modulate neurotransmitter release.

PMID- 7829538
TI  - The beta-adrenoceptor selectivity profile of BRL 37344 in the pithed rat.
AB  - 1. Rats were pithed in order to disrupt baroreflex pathways. Heart rate was used
      as a measure of beta 1-adrenoceptor activity, blood pressure as a measure of beta
      2-adrenoceptor activity and oxygen consumption and brown adipose tissue
      temperature as measures of beta 3-adrenoceptor activity. 2. The effects of the
      selective beta 3-adrenoceptor agonist BRL 37344 were compared with those of
      isoprenaline, a non-selective beta-adrenoceptor agonist, and denopamine and
      salbutamol, which are respectively beta 1 and beta 2-adrenoceptor agonists. 3.
      Denopamine was 10-fold more potent on heart rate than blood pressure, whilst
      salbutamol was 18-fold more potent on blood pressure than heart rate. These
      findings confirm that in this preparation increases in heart rate are
      predominantly beta 1 adrenoceptor-mediated, whilst blood pressure is beta 2
      adrenoceptor-mediated. Further confirmation is provided by the blockade with
      atenolol, of the chronotropic effect, but not the blood pressure effect, of
      isoprenaline. 4. BRL 37344 was the most potent beta-adrenoceptor agonist on both
      oxygen consumption and brown adipose tissue temperature, revealing the beta 3
      nature of these responses. Dose-response curves for oxygen consumption and brown
      adipose tissue temperature were identical, whichever of the beta-adrenoceptor
      agonists was used. Both systems may be considered equally effective as indicators
      of beta 3-adrenoceptor agonist activity.

PMID- 7829539
TI  - Regulation of gastrin release in the dog by alpha 2-adrenoceptors.
AB  - 1. The purpose of the present study was to analyse the effects of the alpha 2
      adrenoceptor agonist medetomidine and the antagonist yohimbine on gastrin release
      in conscious dogs. 2. Gastrin secretion was investigated under both basal
      conditions and stimulation by 2-deoxy-D-glucose, food or bombesin. 3. Basal
      gastrin under fasting conditions was significantly reduced by medetomidine and
      increased by yohimbine. 4. 2-deoxy-D-glucose-induced gastrin increase was fully
      inhibited by medetomidine; this effect was antagonized by yohimbine. 5.
      Medetomidine significantly inhibited food-induced increase in plasma gastrin;
      under these conditions yohimbine was without effect per se, but significantly
      antagonized the inhibitory action of medetomidine. 6. Gastrin release induced by
      bombesin was not affected by medetomidine or yohimbine. 7. These results suggest
      that alpha 2-adrenoceptors play an inhibitory role under conditions in which
      gastrin release is mainly mediated through cholinergic and non-cholinergic
      nervous pathways; in contrast, they do not indicate the presence of alpha 2
      adrenoceptors on G cells of the dog stomach.

PMID- 7829540
TI  - Loss of dopamine D1-like receptors in the umbilical artery of pre-eclamptic
      subjects.
AB  - 1. The influence of pre-eclampsia on the density and pattern of dopamine D1-like
      receptors was studied in frozen samples of the placental end of the umbilical
      artery by using radioligand binding and autoradiographic techniques in
      combination. 2. Analysis was performed on normotensive (n = 10) and pre-eclamptic
      subjects (n = 9) undergoing caesarean delivery, using [3H]-SCH 23390 as a ligand.
      Pre-eclamptic patients received a low salt diet and were treated with magnesium
      sulphate and hydralazine. The possibility that this treatment may cause changes
      in the density of dopamine D1-like receptors was evaluated by treating male
      Wistar rats in the same way and by determining [3H]-SCH 23390 binding in sections
      of the kidney which represents an organ containing dopamine D1-like receptors. 3.
      The density of dopamine D1-like receptors of the umbilical artery, which are
      probably vasodilatory, was decreased in pre-eclamptic compared with normotensive
      subjects. In contrast, the affinity of the radioligand for dopamine D1-like
      receptors was not statistically different between normotensive and pre-eclamptic
      subjects. Low salt diet, magnesium sulphate and hydralazine treatment did not
      affect [3H]-SCH 23390 binding to sections of rat kidney. This suggests that
      changes in the density of dopamine D1-like receptors in pre-eclamptic patients
      are a specific phenomenon not dependent upon antihypertensive measures. 4.
      Analysis of the pharmacological profile of [3H]-SCH 23390 binding to sections of
      the umbilical artery both in normotensive and pre-eclamptic subjects indicates
      the labelling of dopamine D5 receptors. 5. These findings collectively suggest
      that the dopaminergic vasodilatory tone in the umbilical artery is impaired in
      pre-eclampsia. The possible significance of these data should be clarified in
      future studies.

PMID- 7829541
TI  - Skimmianine and related furoquinolines function as antagonists of 5
      hydroxytryptamine receptors in animals.
AB  - 1. Skimmianine, kokusaginine and confusameline, three furoquinolines extracted
      from the leaves of Evodia merrillii (Rutaceae), were investigated to characterize
      their selective effects on subtypes of 5-hydroxytryptamine (5-HT) receptors. 2.
      In the isolated membranes of rat cerebrocortex, using [3H]-5-HT and [3H]
      ketanserin as radioligands, skimmianine and the two other furoquinolines
      displaced radioligand bindings in a concentration-dependent manner. Lower
      concentrations were required to affect [3H]-ketanserin binding than [3H]-5-HT
      binding in the order skimmianine > kokusaginine > confusameline. 3.
      Furoquinolines inhibited 5-HT-induced contraction mediated by 5-HT2 receptors in
      the presence of methiothepin in rat isolated aorta. Also, the combination of
      furoquinolines with ketanserin showed an additive antagonism. 4. These
      furoquinolines were inactive on the 5-carboxamidotryptamine-induced relaxation of
      guinea-pig ileum, a 5-HT1-mediated event. However, 5-HT-induced contraction via 5
      HT2 receptors was reduced by these furoquinolines in a way similar to that in
      blood vessels. 5. The failure of these compounds to affect the 5-HT-induced
      Bezold-Jarisch-like reflex in anaesthetized rats, the major 5-HT3-mediated
      action, ruled out an action on 5-HT3 receptors. 6. The results obtained suggest
      that three furoquinoline alkaloids may act on 5-HT receptors in animals, more
      selectively to the 5-HT2 subtype, in the order of skimmianine > kokusaginine >
      confusameline.

PMID- 7829542
TI  - Developing correlations between fibrinogen adsorption and surface properties
      using multivariate statistics. Student Research Award in the Doctoral Degree
      Candidate Category, 20th annual meeting of the Society for Biomaterials, Boston,
      MA, April 5-9, 1994.
AB  - A multivariate model based on the partial least squares algorithm (PLS) was
      constructed in order to establish a correlation between the surface properties of
      common polymeric materials and the amount and retention of fibrinogen absorbed
      from a complex mixture. Surface characterization was performed by means of static
      secondary ion mass spectroscopy (SIMS), electron spectroscopy for chemical
      analysis (ESCA), and by contact angle measurements of several liquids on those
      materials. 125I-fibrinogen was adsorbed from a 1% plasma solution in buffer and
      the amount adsorbed after 2 h was determined. After 5 days of residence time in
      buffer, the adsorbed fibrinogen was eluted with a 1% solution of the surfactant
      sodium dodecyl sulfate (SDS). The percent of fibrinogen that remained on the
      surfaces after elution is referred to as fibrinogen retention. Correlations
      between surface properties and the amounts of fibrinogen adsorbed or fibrinogen
      retention were established. These models also show the most important variables
      that are related to the protein behavior on these surfaces.

PMID- 7829543
TI  - Recombinant human bone morphogenetic protein-2 is superior to demineralized bone
      matrix in repairing craniotomy defects in rats.
AB  - The purpose of this study was to measure bone-regenerative effects of recombinant
      human bone morphogenetic protein-2 (rhBMP-2) in rat calvarial critical-size
      defects (CSDs). CSDs (8 mm in diameter) were treated with either 1) 2.2
      micrograms rhBMP-2 combined with insoluble collagenous bone matrix (ICBM), 2) 6.5
      micrograms rhBMP-2 plus ICBM, 3) ICBM alone, or 4) demineralized bone matrix
      (DBM), for 7, 14, or 21 days. Multiple linear regression showed that rhBMP-2 had
      a significant time- and dose-dependent effect on bone regeneration (P < .05).
      After 7 days, new calcifying cartilage and remineralizing ICBM, with an
      occasional zone of new woven bone, was evident in defects treated with rhBMP
      2/ICBM. By 14 days, both doses of rhBMP-2 reconstituted with ICBM had induced
      more bone formation than ICBM alone or DBM, and 6.5 micrograms was superior to
      2.2 micrograms. There was no evidence of adverse cellular response. This study
      shows for the first time that rhBMP-2 could restore osseous form to a calvarial
      defect. In addition, osteoregeneration was accelerated by the higher dose of
      rhBMP-2.

PMID- 7829544
TI  - Osseous regeneration in the rat calvarium using novel delivery systems for
      recombinant human bone morphogenetic protein-2 (rhBMP-2).
AB  - In the current investigation, we report osseous regeneration in critical-size rat
      calvarial defects using recombinant human bone morphogenetic protein-2 (rhBMP-2)
      and novel delivery systems based on biomaterials. The novel systems combine rhBMP
      2 with dry powder microparticles of poly(D,L-lactide-co-glycolide) (PLGA). The
      mixture of rhBMP-2 with PLGA microparticles is added to an aqueous solution of
      biopolymer to yield a semisolid paste. The biopolymers tested include autologous
      blood clot, hydroxypropyl methylcellulose, and sodium alginate cross-linked with
      calcium ion. Insoluble collageneous bone matrix was also studied as a control.
      Test articles were made at 0-, 10-, and 30-micrograms doses of rhBMP-2 and
      imiplanted in 8-mm-diameter rat calvarial defects (which will not heal if left
      untreated). The animals were examined 21 days after implantation by radiography,
      radiomorphometry, histology, and histomorphometry. All tested materials
      containing rhBMP-2 restored radiopacity and normal contouring to the calvarial
      defects. Samples without added rhBMP-2 yielded only soft tissue within the
      defects. Histology showed restoration of inner and outer bone tables plus marrow
      constituents. The PLGA microparticles were significantly resorbed at the 21-day
      time point. Although small differences between delivery systems were evident at 0
      and 10-micrograms rhBMP-2 doses, all test articles performed essentially
      equivalently at the 30-micrograms dose. Thus, novel delivery systems for rhBMP-2
      offer the promise of combining the intrinsic bioactivity of the osteoinductive
      protein with pharmaceutically acceptable biomaterials.

PMID- 7829545
TI  - Healing of large segmental defects in rat femurs is aided by RhBMP-2 in PLGA
      matrix.
AB  - Recombinant human bone morphogenetic protein-2 (rhBMP-2) can be used to enhance
      the repair of congenital or acquired bone pathologies when formulated in the
      appropriate carrier. Poly [D,L-(lactide-co-glycolide)] (PLGA) has been shown to
      be an effective carrier of rhBMP-2. We investigated several particle sizes PLGA
      and several doses of rhBMP-2 in a rat orthotopic model. We also investigated the
      effects of a fibrinolytic inhibitory agent, epsilon aminocaproic acid (EACA), on
      the healing response. Our data indicate that higher doses of rhBMP-2 resulted in
      increased failure torque (408 +/- 70 N-mm or 60% of the intact value) and higher
      incidence of union (100%). The induced bone in femurs treated with the smaller
      particle size PLGA achieved the greatest torsional stiffness and strength. The
      presence of rhBMP-2 was necessary for new bone to form, but the presence of EACA
      did not change these results; the use of the PLGA carrier appeared to increase
      bone strength and stiffness. In fact, with higher doses of rhBMP-2 in PLGA, the
      stiffness of the new bone was equal to that of intact controls (64 +/- 20 N
      mm/deg [intact femurs] versus 45 +/- 10 N-mm/degree [medium dose in small PLGA],
      61 +/- 17 N-mm/degree [high dose in small PLGA], and 36 +/- 11 N-mm/degree
      [medium dose in large PLGA]; P > .05). In conclusion, PLGA implanted with rhBMP-2
      effectively aided in healing large segmental defects in rat femurs.

PMID- 7829546
TI  - Photochemical conjugation of mammalian cells to polymeric supports and membranes:
      a kinetic study.
AB  - A commercial polyester acrylate prepolymer, to which a 2:3 wt/wt ratio of
      tripropyleneglycol diacrylate was added to increase photopolymerization rate, was
      employed as photochemical conjugating agent, through photografting. 1,2
      Diphenyl,2,2-dimethoxyethanone was added as standard photoinitiator (7.0 wt/wt%),
      together with varying amounts (0.003-4.0 wt/wt%) of some proprietary
      photocatalytic systems, based on the following photocatalysts: mu-peroxo-bis[N,N'
      ethylene-bis(salicylideneiminato)cobalt(I II) (I), vanadium(V) triethoxide (II),
      and a synergic mixture of vanadium(V) tri-t-butoxide and tri-i-propoxide (III). A
      homogeneous suspension containing (10 +/- 2) x 10(5) human thyroid follicular
      cells per milliliter of photochemically reacting medium was photografted, at a
      surface density of 6.5 +/- 0.7 mg.cm-2 of diacrylate prepolymer mixture, onto
      polystyrene plates or onto commercial microfiltration and ultrafiltration
      membranes consisting of nonwoven cellulose tissues with known porosities varying
      between 5 and 30 microns and in photografted polyester acrylate-based membranes
      with a cutoff of 50 +/- 5 KD. Bioconjugation yields, as a function of
      photografting time, were measured gravimetrically and by multiple internal
      reflection IR spectroscopy. Three series of experiments were performed: 1)
      measurements of graft yields of the prepolymer, and of the parallel disappearance
      of double bonds, in the absence of mammalian cells; 2) the same as 1), in the
      presence of thyroid follicular cells; 3) the same as 2), but with the
      photoinitiating system formed by the standard photoinitiator alone, with no
      photocatalyst. Results show that if a suitable photocatalyst is not added, no
      practical conjugation is possible. An appropriate choice of the photocatalytic
      system and of its concentration allows reduction of irradiation times (e.g., by a
      factor of about 2 x 10(4) calculated as the mean lifetime ratio, between the
      uncatalyzed system and that with 0.1 wt% of [III]), thus minimizing cell
      inactivation and/or improving responsiveness to the bioassay. From this point of
      view, photoactivity of (III) is outstanding. The very small, but clearly
      perceptible, influence of polymeric support on bioconjugation is also commented
      upon.

PMID- 7829547
TI  - Adherent platelet morphology on adsorbed fibrinogen: effects of protein
      incubation time and albumin addition.
AB  - The composition of the protein layer adsorbed to a polymer has been thought to be
      important for the adhesion of platelets. The state of activation of adherent
      platelets is an additional factor that may be a predictor of biocompatibility.
      Activation refers to the degree of change from discoid shape to any of several
      spread shapes. The conformation and orientation of adsorbed adhesive proteins,
      which interact with receptors on the membrane of platelets, such as fibrinogen,
      fibronectin, and von Willebrand factor, may also be important for platelet
      adhesion and activation. This work deals with the behavior of fibrinogen adsorbed
      to PMMA alone, where the experimental variable was incubation time with the
      substrate, and with adsorbed fibrinogen mixed with albumin, where the
      experimental variable was the molar percent of fibrinogen in the adsorption
      solution. Shorter protein incubation times and increased albumin levels in the
      initial fibrinogen adsorption solution enhanced the percentages of activated
      platelet morphologies and increased adsorbed fibrinogen redistribution by the
      platelet. Lower concentrations of albumin in the initial adsorption solution
      enhanced platelet adhesion numbers; fibrinogen incubation time had no effect.
      Together, these factors can contribute to the biocompatibility of a biomaterial
      through their effect on platelet adhesion and activation.

PMID- 7829548
TI  - Biodegradation evaluation of polyether and polyester-urethanes with oxidative and
      hydrolytic enzymes.
AB  - Enzyme-induced liberation of components from seven different radiolabeled
      polyurethanes was monitored by radiolabel counting of the incubation solutions
      and product isolation by high performance liquid chromatography (HPLC). The
      polyurethanes were selected to reflect variations in the hard-segment chemistry,
      soft-segment chemistry, and polyurethane hydrophilicity resulting from
      combinations of hydrophobic/hydrophilic soft segments. All materials were
      characterized using electron spectroscopy for chemical analysis, differential
      scanning calorimetry, size exclusion chromatography, and Fourier transform
      infrared spectroscopy. The material surfaces were examined both before and after
      incubation with enzyme and control solutions using scanning electron microscopy.
      Biodegradation assays were carried out at 37 degrees C using cholesterol esterase
      (CE) and horseradish peroxidase (HRP) under optimal pH conditions for each
      enzyme. The hydrolytic enzyme (CE) was effective in releasing degradation
      products that contained hard-segment components from some of the polyurethanes.
      HPLC analysis of products for a polyesterurethane synthesized with toluene
      diisocyanate (TDI) suggested that the bulk of the incorporated radiolabeled TDI
      was still covalently bonded within the cleaved chain segments of the original
      polymer and was not released as pure toluene diamine (TDA). The data suggest that
      urethane linkages in the soft-segment domains of phase separated polyetherurea
      urethanes may be more prone to cleavage by CE than are the urea/urethane groups
      in the hard-segment domains. This could be related to the nature of the hard
      segment domain structures. The oxidative enzyme (HRP) was not able to induce
      liberation of radiolabeled segments from either the polyether or polyester-based
      polyurethanes.

PMID- 7829549
TI  - Strategy for developing microbeads applicable to islet xenotransplantation into a
      spontaneous diabetic NOD mouse.
AB  - A bioartificial pancreas (BAP) created through the encapsulation of islets of
      Langerhans (islets) in a semipermeable membrane has been proposed as a promising
      approach to treating insulin-dependent diabetes patients. A nonobese diabetic
      (NOD) mouse, which shares many features of human insulin-dependent diabetes
      mellitus, is an ideal model for evaluating the function of BAP. However, the
      functions of BAPs that have been developed have been limited in NOD mice. We
      propose novel microbeads that can realize long-term BAP function in NOD mice. The
      novel microbeads were composed of agarose and poly(styrene sulfonic acid) (PSSa)
      mixed gel. A polyion complex layer between PSSa and polycationic polybrene was
      formed on and just inside the microbead, and the microbead surfaces were further
      covered by polyanions to produce anionic surface charges. The islets in the novel
      microbeads were intraperitoneally implanted. Graft-functioning periods were
      dependent on both PSSa concentration and the kinds of polyanion. Islets in the
      microbeads composed of 5% agarose and 5% PSSa, which had an outermost surface
      covered by carboxymethyl cellulose, produced normoglycemic periods of more than
      60 days in all five recipients. Control mice receiving either transplants of
      unenclosed islets or islets in agarose microbeads showed normoglycemic periods of
      less than 12 days. We believe that agarose/PSSa microbeads are promising for
      producing semipermeable membranes that enable xenotransplantation of islets in
      spontaneous diabetes mellitus.

PMID- 7829550
TI  - Materials testing protocol for small joint prostheses.
AB  - In this article, a protocol for the evaluation of new materials for small joint
      prostheses is introduced. The testing methods employed in the protocol were
      developed by reviewing reported clinical failure modes and conditions found in
      vivo. The methods developed quantitatively evaluates the fatigue, fatigue crack
      propagation, and wear resistance properties of materials. For this study, a
      silicone elastomer similar to Dow Corning Silastic HP100, a radiation stable
      polypropylene, and a copolymer of polypropylene and ethylene propylene-diene
      monomer (EPDM) are evaluated. None of the materials tested demonstrated the ideal
      properties that are sought in a self-hinging joint prostheses. The silicone
      elastomer had excellent wear properties; however, cracks quickly propagated,
      causing catastrophic failure when fatigued. Conversely, the copolymer showed
      excellent fatigue crack propagation resistance and less than favorable wear
      properties. The polypropylene did not perform well in any evaluation.

PMID- 7829551
TI  - Long-term durability of the interface in FRP composites after exposure to
      simulated physiologic saline environments.
AB  - Fiber/matrix interfacial bond strength significantly influences the mechanical
      behavior of fiber-reinforced polymer (FRP) composites. Interfacial bond strength
      durability is therefore particularly important in the development of FRP
      composites for implant applications where diffused moisture may potentially
      weaken the material over time. In this study, the long-term durability of
      interfacial bonding in carbon fiber/380 grade polyetheretherketone (C/PEEK) and
      carbon fiber/polysulfone (C/PSF) composites was investigated after exposure to
      hygrothermal environments. A single fiber pull-out test was used to
      quantitatively determine the ultimate bond strength (UBS) of the samples
      following exposure. Samples were tested at three temperatures (37, 65, and 95
      degrees C) for six time periods (0-5000 h) and in two environments (dry and
      physiologic saline-immersed). A mathematical model based on nth order chemical
      reaction kinetics was applied to describe the long-term durability of the
      interface. The results of this study indicate that interfacial bond strengths in
      C/PSF and C/PEEK (380 grade) composites are significantly decreased by exposure
      to physiologic saline and are functions of both time and temperature. For each
      material, the kinetics of degradation analysis predicts further bond strength
      losses following initial saturation, which then stabilizes at temperature
      dependent equilibrium bond strength levels.

PMID- 7829552
TI  - Comparison of tissue factor and prostacyclin production by human umbilical vein
      endothelial cells on Dacron vascular prostheses and Dacron smooth films.
AB  - The functional capacity of human umbilical vein endothelial cells (HUVEC) grown
      on Dacron (polyethylene terephthalate; PET) vascular prosthetic material was
      compared with the function of cells on smooth surfaced PET, tissue culture
      polystyrene (TCPS), and Natrix-coated TCPS. Prosthetic materials include two
      knitted fabrics (Bionit I and II) and two woven preparations (DeBakey Soft Woven
      and Extra Low Porosity). Two entities produced by HUVEC that influence blood
      coagulation were assessed: the procoagulant tissue factor (TF) and the
      anticoagulant prostacyclin (PGI2). Although TF activity was stimulated on all
      substrates by endotoxin (LPS), there was no difference among prostheses and no
      difference among smooth surface materials, but TF was reduced in cells on the
      prosthetic materials relative to those on smooth surface substrates. The reduced
      TF production by HUVEC on prosthetic material could be reversed by returning them
      to TCPS. In contrast, PGI2 production on prostheses was comparable to that on
      smooth surfaces for both stimulated and unstimulated cells. Stimulation with
      histamine (1 microM) gave a 2.4-fold increase in PGI2 whereas mellitin (10
      micrograms/ml) increased production 12.5-fold. The differential response of HUVEC
      with regard to these two coagulation factors, one of which is secreted and the
      other membrane bound, may reflect the distorted shape of cells on fibers of the
      prosthesis.

PMID- 7829553
TI  - Thermal stability of sodium hyaluronate in aqueous solution.
AB  - Since its identification 60 years ago as a ubiquitous component of the body of
      mammals, hyaluronic acid has been widely studied, primarily in the fields of
      medicine and biology. On the other hand, our research has dealt with hyaluronic
      acid as a chemical intermediate in the synthesis of novel lubricious coatings,
      and in this connection data were needed on stability of aqueous solutions of the
      polymer over a range of temperatures from 25-100 degrees C. The investigation
      reported here provides that information, obtained by exposing samples in sealed
      ampules in baths at controlled temperatures and determining the resulting change
      in viscosity of the solutions. Data of this kind have not previously been
      reported on sodium hyaluronate freed from the proteins and other organics
      normally associated with the polymer in its natural environment.

PMID- 7829554
TI  - Detection of antibodies against corrosion products in patients after Co-Cr total
      joint replacements.
AB  - Sensitivity to nickel, cobalt, and chromium is common among the general
      population. The identification of these sensitivities is generally by the
      detection of cell-mediated immunity. Detection of humoral immunity to these
      metals has rarely been undertaken because suitable assays are not available. To
      further our knowledge about the systemic humoral immune system response to weak
      hapten-syngeneic or allogeneic protein conjugates (corrosion and wear products of
      metallic orthopedic devices), a sensitive enzyme-linked immunosorbent assay
      (ELISA) method for testing for antibody (humoral immunity) to metals was
      developed. Microtiter plates were coated with human serum albumin (HSA) or
      glutathione (GSH) and then conjugated with metal ions. Plates coated with HSA or
      GSH and without metal ions served as background controls. An indirect ELISA
      method was used to detect antibody binding. Patients bearing cobalt-chromium
      alloy devices were considered to be the most likely candidates as sources of
      antibody to metal and were used to document the usefulness of the test.
      Specificity of the test was documented by inhibition studies with these metal
      ions in the ELISA assay. The serum samples of 10 patients were screened for the
      presence of Cr-, Co-, or Ni-specific antibody at various periods up to 5.5 years
      after implantation of F-75 cobalt alloy total joint replacements. All patients
      had implants that were functioning well. The pre- and postimplantation humoral
      immune profiles of patients were determined and compared with each
      preimplantation control and with a pooled normal serum sample. This study
      presents evidence that metal-protein complex-specific antibodies can be detected.
      The clinical implications remain to be determined.

PMID- 7829555
TI  - Studies on two new radiopaque polymeric biomaterials.
AB  - Two new polymeric materials (polymers A and B) containing covalently bound iodine
      were prepared. These polymers were evaluated with respect to their possible use
      as radiopaque implant biomaterials--that is, materials that are visible in a
      noninvasive manner using routine X-ray absorption imaging techniques. Polymer A
      is a copolymer of methyl methacrylate (MMA) and 1 (80 and 20 mol%, respectively).
      Polymer B was prepared from MMA, 1, and 2-hydroxyethyl methacrylate (HEMA) (mol
      ratio 65:20:15, respectively). Compound 1 was synthesized from 4-iodophenol and
      methacryloyl chloride. The resulting polymers were characterized with GPC, DSC,
      NMR, and by measuring both the advancing and receding contact angles.
      Thrombogenicity of the polymers was determined by an in vitro thrombin generation
      test procedure. The maximum concentration of free thrombin was 76 +/- 1 nM for
      polymer A, and 64 +/- 3 nM for polymer B. The lag times (i.e., time onset of
      thrombin generation) were 392 seconds for polymer A and 553 seconds for polymer
      B. For PVC-T, which is known as a passive material, a lag time of 583 seconds was
      found. This indicates that polymer B is comparable to PVC-T, and more passive
      than polymer A. Polymer A exhibited minor activation of platelets. Polymer B did
      not induce platelet activation at all. The polymers exhibited, even as fibers
      with a diameter of ca. 0.3 mm, good radiopacity with routine imaging X-ray
      techniques in the clinic.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7829556
TI  - Analysis of the general features of the soft tissue response to some metals and
      ceramics using quantitative histomorphometry.
AB  - This article analyzes the general features of the tissue response to orthopedic
      biomaterials when implanted in the paraspinal muscles in rats for periods between
      1 week and 1 year. Using a computer-assisted cell counting method, it was shown
      that the membrane thickness was a stable parameter that poorly correlated with
      the other histomorphometric parameters except fibrocyte distance parameters.
      Macrophages were significant in number only in the short term and were always
      located at the implant-tissue interface. At 4 weeks, the period corresponding to
      which macrophages disappeared, fibrocytes were found nearer the interface than at
      earlier periods and did not migrate for up to 52 weeks, although their densities
      decreased to 50% of their initial values. Therefore, it can be
      histomorphometrically confirmed that 1) the presence of an implant induced a
      delay in the healing process; 2) the immune system was not usually involved in
      the response to bulk metals; and 3) at early time periods, the presence of PMN
      cells was correlated to the long-term number of macrophages. On the contrary, the
      histomorphometric findings suggested that around the tested materials, a large
      number of macrophages did not induce an immediate or a delayed fibrocyte
      proliferation. If one considers that a low fibrocyte surface density is related
      to activated cells surrounded by a matrix high in collagen content, then the
      large number of macrophages induced the stimulation of collagen synthesis by the
      fibrocytes already included in the membrane. Accordingly, in the short-term, a
      high fibrocyte density and few macrophages may be a criterion for testing
      biocompatibility.

PMID- 7829557
TI  - Isolation and characterization of metallic wear debris from a dynamic
      intervertebral disc prosthesis.
AB  - A dynamic intervertebral disc prosthesis (DIDP) has been developed. It consists
      of a CoCrMo body and uses Ti6Al4V springs to replicate the mechanical function of
      the lumbar joint. Wear studies have been performed previously on the DIDP using
      two specialized simulators to test the wear properties of the moving parts of the
      disc prosthesis. A pin-in-slot simulator generates wear that would occur in the
      hinge-pin assembly of the prosthesis. A spring-in-pocket simulator approximates
      the conditions under which the springs would wear against the body of the
      prosthesis. The spring-pocket interface is responsible for the production of
      approximately 90% of the total wear occurring in the prosthesis, and is therefore
      the main focus of this study. Bovine serum with a preservative has been used as a
      lubricant in both simulators. The spring-in-pocket simulator compares the effects
      of two different manufacturing techniques of CoCrMo (HIPing and forging) on their
      wear characteristics against Ti6Al4V springs. Debris from the spring-in-pocket
      simulator has been isolated from the serum lubricant and characterized using
      scanning electron microscopy techniques. The morphology of the Ti6Al4V fragments
      is rough and irregularly shaped. The size of these fragments ranges from < 1
      microns to > 30 microns. The forged CoCrMo alloy debris has an irregular
      polyhedral shape, with sizes in the same range as the spring fragments. The
      morphology of the HIPed CoCrMo debris is spherical with a size range < 5 microns
      to > 30 microns. Length and width measurements of micron-size particles were made
      with the particle measurements feature of the scanning electron microscope.
      Micron-size particles were found in all stations. This article provides a unique
      way to isolate and analyze debris from serum lubricants used in simulators.

PMID- 7829558
TI  - Inhibition of Staphylococcus adherence to biomaterials by extracellular slime of
      S. epidermidis RP12.
AB  - Adherence of selected strains of coagulase-negative staphylococci to various
      biomaterials, and the inhibition of their adherence by extracellular slime
      obtained from the RP12 strain of Staphylococcus epidermidis were studied in
      vitro. S. epidermidis RP12 adhered considerably more to polymethylmethacrylate
      (PMMA) discs than did the SP2 strain of S. hominis and the SE-360 strain of S.
      hyicus. Strain RP12 was less adherent to titanium alloy, ultrahigh molecular
      weight polyethylene (UHMWPE), and Teflon discs than to PMMA discs. Exposure of
      PMMA discs to extracellular slime extracted from strain RP12 greatly reduced
      adherence of strain RP12, SP2, SE-360, and S. epidermidis RP-62A. The active
      component(s) was present in the > 10 kD mol wt fraction obtained by Amicon YM10
      ultrafiltration of crude slime; heat treatment of the fraction did not affect its
      inhibitory activity. When the bacteria and RP12 slime fractions were added
      simultaneously to the PMMA discs, the > 10 kD mol wt fraction of slime
      competitively inhibited adherence of strain RP12 to PMMA discs; in contrast, the
      < 10 kD mol wt fraction enhanced adherence of strain RP12 to PMMA discs.

PMID- 7829559
TI  - Mineralization of alkaline phosphatase-complexed collagenous implants in the rat:
      relation with age, sex, and site of implantation.
AB  - This study was designed to determine the effects of age, sex, and site of
      implantation on the extent of alkaline phosphatase-complexed collagen sheets
      mineralization in the animal body. Collagen sheets were prepared from bovine
      dentin and cortical bone and complexed with varying amounts of intestinal
      alkaline phosphatase (ALP). Controls were without enzyme or with heat-inactivated
      enzyme. Sheets were implanted subcutaneously over the skull and in the
      dorsolateral abdominal wall in 5- or 20-week-old male and female Wistar rats.
      After 2-3 weeks the implants were removed and analyzed for phosphate and calcium
      content. Our findings have shown that alkaline phosphatase-induced mineralization
      of collagenous implants is influenced to a considerable extent by age, sex, and
      site of implantation. Highest mineral influx was seen in the younger males.
      Implants in younger females and older males contained less mineral, whereas those
      installed in the older females were almost free of calcium phosphate deposits.
      Dentinal implants in the skull region contained more mineral than those in the
      abdominal wall.

PMID- 7829560
TI  - Effect of bioactive ceramic composition and structure on in vitro behavior. III.
      Porous versus dense ceramics.
AB  - In vitro reaction kinetics of surface transformations of porous and dense
      bioactive ceramics were studied after immersion in simulated physiologic solution
      (SPS). Porous ceramics with identical macroporosity were commercially obtained:
      calcium carbonate marine coral (I-CC), coralline HA (I-HA), and a product,
      labeled as beta-tricalcium phosphate, which was partially transformed into beta
      calcium pyrophosphate (I-beta-CP). Previously studied dense ceramics were used
      for comparison: Ca-deficient HA (CDHA), stoichiometric HA, both well and not well
      crystallized (wc and nwc s-HA), beta- and alpha-tricalcium phosphate (beta- and
      alpha-TCP). The induction time to precipitation increased as follows: CDHA, nwc
      HA < wc HA, I-HA < beta-TCP, I-CC << I-beta-CP. The reaction kinetics of ceramics
      with identical macroporosity varied substantially depending on composition,
      crystal structure, and ultrastructure. One of the porous ceramics, I-beta-CP,
      showed an inhibiting effect on precipitation reactions.

PMID- 7829561
TI  - Effect of Ca/P coating resorption and surgical fit on the bone/implant interface.
AB  - The effect of coating resorption on bone apposition and attachment strength to
      resorbable hydroxyapatite (HA), nonresorbable HA-coated, and uncoated rough
      titanium implants was evaluated in interference- and noninterference-fit (gap of
      2-3 mm) surgical models 2, 4, and 12 weeks postoperatively. Interference and
      noninterference fits showed differences in bone bridging. Bone apposition was
      circumferential around the implants in noninterference fit. Significantly greater
      bone apposition was seen to nonresorbable HA-coated implants than uncoated and
      resorbable HA-coated implants at 4 and 12 weeks. Only resorbable HA coatings
      showed significantly lower bone apposition for noninterference versus
      interference fit and from 4-12 weeks. At 2 weeks, strengths of bone attachment to
      resorbable HA-coated implants were greater than the other implants, and decreased
      to lower values (not significant) than the nonresorbable HA-coated implants at 4
      and 12 weeks. Differences in push-out shear strengths between interference- and
      noninterference-fit surgical models were significant for uncoated implants at 4
      weeks, but not for HA-coated implants at any time period. Significant differences
      were seen between the three implant types only for the noninterference-fit model,
      where the HA-coated implants showed greater strengths than the uncoated implants
      (significant at 2 and 4 weeks). This study showed that presence of resorbable or
      nonresorbable HA coatings is beneficial when a gap of 2-3 mm is present between
      the implant and the bone. The resorbable HA-coated implants showed greatest
      strengths at the early time period. At later time periods, resorbable HA-coated
      implants showed lower bone apposition and attachment strengths than nonresorbable
      HA coatings.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7829562
TI  - Titanium fiber mesh anchorage for percutaneous devices applicable for peritoneal
      dialysis.
AB  - In previous experiments a new type of percutaneous device for implantation in
      soft tissue was designed. The subcutaneous component of the new device consists
      of a sintered titanium fiber web. The percutaneous devices are inserted by a so
      called "two-phase" surgical technique with an intervening healing period of 3
      months between the insertion of the subcutaneous flange and the placement of the
      percutaneous part. From a clinical point of view, this time interval is too long.
      Therefore, the aim of this study was to investigate a possible reduction of the
      intervening healing period. The implants were inserted in the backs of 18
      rabbits. In each rabbit, six implants were placed with intervals of 1 week.
      Consequently, at the end of the experiment, in each rabbit six implants were
      present with implantation periods ranging from 5-10 weeks. After 10 weeks, the
      animals were sacrificed and the implants with their surrounding tissues were
      processed histologically. Light microscopic and histomorphometric analysis
      demonstrated that there was no difference in tissue response between the various
      implantation periods. Furthermore, it was found that the fiber mesh material
      showed good biocompatible behavior. In conclusion, the experiment has
      demonstrated that for titanium mesh percutaneous devices a 5-week healing period
      is sufficient between the installation of the subcutaneous and percutaneous
      parts.

PMID- 7829563
TI  - Correlations between orthogonal mechanical properties and density of trabecular
      bone: use of different densitometric measures.
AB  - To compare the numerous modulus-density and strength-density relations that have
      been found for human trabecular bone from the proximal tibia, correlations
      between various measures of density were sought. Hydrated and dry apparent
      density, ash density, and density from quantitative computed tomography (QCT)
      were determined for cubic trabecular specimens taken from the proximal portion of
      human tibiae, and correlations between these measures were found (r > 0.99, P <
      .001). Orthogonal moduli and strengths of the specimens were measured
      mechanically, and were significantly correlated with ash density according to
      power relations (r > or = 0.85, P < .001). The strong correlation between density
      from QCT and ash density indicates that these measures can be used with nearly
      equal precision in estimating modulus and strength of tibial trabecular bone.
      Equations between mechanical properties and density reported in previous studies
      were converted to use a common density measure and, after considering the effects
      of specimen size, were in general agreement with results of the present study.

PMID- 7829564
TI  - Dissolution/reprecipitation and protein adsorption studies of calcium phosphate
      coatings by FT-IR/ATR techniques.
AB  - The surfaces of bioactive Ca-P ceramics immediately change when exposed to
      proteinaceous solutions. The dissolution behavior and protein interactions of
      these bioactive materials at the bone/implant interface need to be investigated
      to understand their material-cellular interactions fully. In this study, FT
      IR/ATR techniques were used to study the in situ phosphate release kinetics of Ca
      P coatings. The net loss of phosphate molecules from coatings was slower in
      saline solutions compared with alpha-MEM solutions. Coatings exposed to alpha-MEM
      solutions containing fibronectin released phosphate molecules slower than
      coatings exposed to alpha-MEM solutions containing albumin. Conformational
      changes in fibronectin and albumin adsorbed onto Ca-P and uncoated germanium
      surfaces were also investigated using FT-IR/ATR spectroscopy. Analysis of changes
      in the amide I bands indicated that there was a greater loss of beta-sheet
      structure in adsorbed fibronectin on Ca-P coatings when compared with bare
      germanium surfaces. Although albumin did change its structure upon adsorption on
      both Ca-P and germanium, unlike fibronectin, adsorbed albumin structure was
      similar on Ca-P coatings and germanium. Furthermore, with time the conformation
      of adsorbed fibronectin and albumin appeared to be very stable on Ca-P coatings,
      whereas albumin adsorbed to germanium exhibited an increase in ratio of alpha
      helix to beta-turn.

PMID- 7829565
TI  - Selective adhesion of platelets on a polyion complex composed of phospholipid
      polymers containing sulfonate groups and quarternary ammonium groups.
AB  - We investigated the effects of electrical charges on cell-polymer interactions of
      poly[2-methacryloyloxyethyl phosphorylcholine(MPC)-co-n-butyl methacrylate (BMA)]
      (PMB) having excellent blood compatibility, by copolymerizing anionic or cationic
      methacrylates with MPC and BMA. A polyion complex (PIC) composed of anionic and
      cationic MPC copolymers was also prepared. When the cell adhesion on these
      polymer surfaces from rabbit whole blood was evaluated, we observed a
      considerable reduction in cell adhesion on the MPC copolymers compared with that
      on poly(BMA), even when the MPC copolymer was electrically charged. On the other
      hand, many platelets selectively adhered to the PIC surface from whole blood, but
      the adherent platelets maintained a discoid shape. The amount of adenosine
      triphosphate (ATP) in platelets adherent on the PMB or the PIC from a platelet
      rich plasma (PRP) was more than 75% of that in the original PRP, which indicated
      that the activity of these platelets remained high. However, in the platelets
      adherent to poly(BMA), only a small amount of ATP remained. Protein adsorption on
      the polymer surface from human plasma was investigated using a gold-colloid
      labeled immunoassay against albumin gamma-globulin, and fibrinogen. Many of these
      proteins adsorbed on poly(BMA), whereas a small amount of protein was observed on
      the MPC copolymers that had an electrical charge. Albumin adsorption and
      suppression of gamma-globulin and fibrinogen adsorption were found on the PIC.
      Therefore, the introduction of electrical charges in the PMB did not have an
      adverse effect on cell adhesion and protein adsorption.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7829566
TI  - Osteoclastic resorption of apatite formed on apatite- and wollastonite-containing
      glass-ceramic by a simulated body fluid.
AB  - We immersed mirror-polished apatite- and wollastonite-containing glass-ceramic (A
      W GC) disks in a simulated body fluid (SBF) for 5 days to form bonelike apatite
      on their surface. Neonatal rabbit bone cells were cultured on these or on plain A
      W GC disks for 10, 24, and 48 h. We observed the substrates by scanning electron
      microscopy after treating them with pronase E plus EDTA to remove all cells
      except osteoclasts. Osteoclasts with a non-motile appearance formed no lacunae on
      the plain A-W GC, whereas on the bonelike apatite formed on A-W GC by the SBF,
      actively moving osteoclasts made many tracklike resorption lacunae. These were
      evident even after 10 h of culture and became more extensive after longer culture
      periods. The bonelike apatite was therefore a more suitable medium than plain A-W
      GC for maintaining osteoclast activity. This study demonstrated in vitro
      osteoclastic resorption of bonelike apatite formed on A-W GC by an SBF. It
      suggests that the apatite layer, through which a surface-active ceramic bonds to
      bone in vivo, can be resorbed by osteoclasts and subjected to bone remodeling.

PMID- 7829567
TI  - In vitro hydroxyapatite deposition onto a film surface-grated with
      organophosphate polymer.
AB  - To produce a bone-bonding polymer surface that is capable of inducing deposition
      of a hydroxyapatite (HA) layer in the body fluid, an organophosphate polymer was
      covalently immobilized onto a high-density polyethylene film by surface graft
      polymerization of a phosphate-containing monomer. The grafted film was immersed
      in simulated physiologic solution (SPS). The chemical composition and structure
      of the formed apatite layer as well as its bonding strength to the polymer
      surface were investigated. To distinguish the effect of phosphate groups on the
      deposition of apatite layer from the simple calcium absorption by the anion, a
      comparative study was done using a polyethylene film with surface immobilized
      carboxylic groups. Calcium phosphate deposition was observed on all the materials
      investigated, but the kinetics, composition, deposit amount, and bonding strength
      of the new phase were found to be significantly different among the modified
      materials, depending on the density and chemical nature of the surface
      immobilized ionic groups. It was found that the polymeric materials modified by
      surface graft polymerization of a phosphate-containing monomer produce a
      carbonated HA layer firmly bonded with the material upon immersion in SPS.
      Carboxyl groups in the grafted layer was not enough to activate bonding with the
      HA layer.

PMID- 7829568
TI  - Interaction of chlorhexidine digluconate with and adsorption of chlorhexidine on
      hydroxyapatite.
AB  - It is well known that chlorhexidine digluconate provides an effective
      microbicidal activity during oral rinsing, and therefore, it was considered
      worthwhile to investigate its interaction with hydroxyapatite on a fundamental
      level. The kinetics of uptake (or reaction) of the compound from aqueous
      solutions by synthetic hydroxyapatite was studied at 23 degrees C for four time
      periods by monitoring its concentration. There was no uptake at low
      concentrations for any time period. The uptake curves for higher concentrations
      shifted towards the lower concentrations as the period increased and became more
      and more vertically oriented to the concentration axis. The concentrations of
      calcium ions increased, phosphate ions decreased and hydrogen ions decreased a
      little for a given period as the concentration of the compound was increased. All
      of these experimental facts can be qualitatively explained on the basis of the
      solubility considerations of hydroxyapatite and of chlorhexidine phosphate, the
      reaction product that slowly precipitates out of the solution. The needle-shaped
      birefringent crystals of the phosphate salt are clearly visible in the apatite
      matrix under a microscope, and its refractive index and differential Fourier
      transform infrared spectra match almost exactly with those of a well
      characterized, synthesized phosphate salt. To explore the nature of interaction,
      the uptake of chlorhexidine base was studied from p-dioxane and it is
      irreversible. The uptake is total below a threshold equilibrium concentration and
      constant above it.

PMID- 7829569
TI  - Biotechnology applications in biomaterials.

PMID- 7829570
TI  - Introductory remarks to the biotechnology applications in biomaterials workshop.

PMID- 7829571
TI  - Biotechnology meets biomaterials.

PMID- 7829572
TI  - Manipulation of cellular interactions with biomaterials toward a therapeutic
      outcome: a perspective.
AB  - Manipulation of the wound healing process and the manner in which tissues
      interact with inert biomaterials were both made possible with the discovery of
      arginine-glycine-aspartic (RGD) acid as a major cell recognition signal in the
      extracellular matrix. Whether promoting cell adhesion or selectively inhibiting
      cell-cell aggregation mediated by integrin cell surface receptors, RGD-containing
      peptides can be rationally designed to incorporate both stability and integrin
      specificity. Synthetic peptides containing this sequence have been linked to
      biodegradable biopolymers and introduced for the enhancement of dermal and
      corneal would healing. By accelerating the healing reaction using RGD-containing
      peptides, the quality of regenerated tissue seems to be improved, the extent of
      fibrosis restricted, and the risk of microbial infection may be reduced.
      Controlling the degree of fibrosis that often accompanies the healing of wounds
      and the reaction of tissue to foreign materials can also be achieved by natural
      antagonists of fibrogenic activity of TGF-beta animal models of kidney fibrosis.
      These advances in the biotechnology of wound healing and tissue regeneration
      eventually will have an overall impact on the quality of health care.

PMID- 7829573
TI  - Polymer substrates for controlled biological interactions.
AB  - The identification of a myriad of small peptide and carbohydrate ligands
      recognized by cell surface receptors has generated enthusiasm for the use of
      these ligands of components of biomaterials for controlling cellular
      interactions. Achieving control of cell interactions via ligand modification of
      materials also requires that nonspecific interactions of cells with these
      materials due to surface adsorption of biological macromolecules is minimized.
      Polyethylene oxide (PEO) exhibits extraordinary inertness toward most biological
      macromolecules and is thus receiving increasing attention as a component of new
      materials for controlling cell behavior. Both surface and bulk modifications with
      PEO are being applied to develop a range of bland substrate materials as vehicles
      for ligand immobilization.

PMID- 7829574
TI  - Effect of bioactive glass templates on osteoblast proliferation and in vitro
      synthesis of bone-like tissue.
AB  - Using in vitro synthesized bone tissue with cells aspirated from the patient's
      marrow is an appealing idea to avoid the profound limitations of biological and
      synthetic grafts. Procedures to synthesize bone tissue in vitro primarily relied
      on seeding various substrates with cells that have osteogenic capacity in
      culture. It should be noted that in an in vitro system, osteoprogenitor cells, as
      well as bone cells themselves can rapidly change their phenotype, hence the
      substrate needs to promote the expression of the bone cell phenotype.
      Furthermore, it needs to provide a template for bone deposition while gradually
      resorbing once bone tissue has been laid down. This paper presents initial
      evidence that bioactive glass, a synthetic material with documented extensive
      bone bioactivity properties, represents a material that optimally combines the
      requirements of the ideal template for in vitro synthesis of bone tissue. When
      made in porous form, and conditioned to develop a bone-like surface prior to
      being seeded with pluripotential cells capable of expressing the osteoblastic
      phenotype, these templates lead to expeditious and abundant in vitro synthesis of
      extracellular matrix with most important characteristics of bone tissue.

PMID- 7829575
TI  - Self-assembling biomolecular materials in medicine.
AB  - Materials that mimic or extend the properties of natural molecules are being
      developed for medical applications. Recent breakthroughs in genetic engineering,
      polymer synthesis, molecular self-assembly and related areas are greatly
      expanding the variety of structures available for use in physiological settings.

PMID- 7829576
TI  - Two-dimensional protein crystals (S-layers): fundamentals and applications.
AB  - Two-dimensional crystalline surface layers (S-layers) composed of protein or
      glycoprotein subunits are one of the most commonly observed prokaryotic cell
      envelope structures. Isolated S-layer subunits are endowed with the ability to
      assemble into monomolecular arrays in suspension, on surfaces or interfaces by an
      entropy-driven process. S-layer lattices are isoporous structures with functional
      groups located on the surface in an identical position and orientation. These
      characteristic features have already led to applications of S-layers as (1)
      ultrafiltration membranes with well-defined molecular weight cut-offs and
      excellent antifouling characteristics, (2) immobilization matrices for functional
      molecules as required for affinity and enzyme membranes, affinity microcarriers
      and biosensors, (3) conjugate vaccines, (4) carriers for Langmuir-Blodgett films
      and reconstituted biological membranes, and (5) patterning elements in molecular
      nanotechnology.

PMID- 7829577
TI  - Triggers and switches in a self-assembling pore-forming protein.
AB  - Protein engineering is being used to produce a collection of pore-forming
      proteins with applications in biotechnology. Knowledge provided by investigations
      of the mechanism of self-assembly of staphylococcal alpha-hemolysin has allowed
      the design of genetically and chemically modified variants of the protein with
      pore-forming activities that can be triggered or switched on-and-off by chemical,
      biochemical and physical inputs. Examples include alpha-hemolysins that are
      activated by specific proteases and alpha a-hemolysins whose activity is
      controlled by divalent metal ions. These proteins have potential value in drug
      delivery as components of immunotoxins that can be activated at the surfaces of
      target cells. Further applications are likely in improved encapsulation
      techniques for drugs, enzymes and cells.

PMID- 7829578
TI  - Biomaterial biotechnology using self-assembled lipid microstructures.
AB  - Lipids are a class of molecules which self-assemble into a variety of phase
      dependent morphologies. We have employed self-assembled lipid microstructures in
      the development of a number of biomedical material applications. The blood
      substitute, liposome encapsulated hemoglobin, is being investigated for the in
      vivo delivery of hemoglobin without many of the inherent toxicities associated
      with the delivery of free hemoglobin. This investigation is currently focused on
      demonstrations of efficacy in stressed animal models and on the safety of
      administering this material in models of sepsis. The synthetic modification of
      phospholipids to include photopolymerizable moieties such as diacetylenes has
      resulted in the spontaneous self-assembly of a hollow microcylinder which we are
      investigating for the controlled release of growth factors in soft tissue
      regeneration. Self-assembled monolayers are also being explored for the ability
      to surface modify biomaterials for improved cell adhesion. Photolithographic
      techniques have been combined with monolayer deposition to fabricate coplanar
      patterns of cell adhesion and inhibiting moieties. This results in the ability to
      spatially control the adhesion of cells to biomaterial surfaces. These cell
      patterns can form the basis for understanding two- and three-dimensional cellular
      events on the biomaterial surface and for the fabrication of improved cell-based
      biocompatible surfaces. The spontaneous self-assembly of lipids to form
      structures of biotechnological interest presents a unique opportunity to exploit
      this class of molecules for biomaterial applications.

PMID- 7829579
TI  - Applications of ECM analogs in surgery.
AB  - The loss of tissue mass in humans has been conventionally treated as an
      irreversible change. Treatments have emphasized replacement of the missing
      function by use of a transplant, an autograft, tissue synthesized in vitro or,
      most commonly, by use of engineering devices based on biomaterials. During the
      last few years solid progress has been made in the area of tissue and organ
      regeneration. This new approach is based on the discovery that certain simple
      chemical analogs of extracellular matrices synthesized by graft copolymerization
      of a glycosaminoglycan onto type I collagen can induce synthesis of physiologic
      tissue in lesions which otherwise heal spontaneously by synthesis of scar tissue.
      This approach offers serious potential advantages over the alternatives listed
      above since the graft "grows out" of host tissue. However, regeneration in the
      adult mammal has been successfully demonstrated so far only in skin (human,
      guinea pig), sciatic nerve (rat) and the knee meniscus (dog).

PMID- 7829580
TI  - Symbiosis of biotechnology and biomaterials: applications in tissue engineering
      of bone and cartilage.
AB  - The three ingredients for the successful tissue engineering of bone and cartilage
      are regulatory signals, cells, and extracellular matrix. Recent advances in
      cellular and molecular biology of the growth and differentiation factors have set
      the stage for a symbiosis of biotechnology and biomaterials. Recent advances
      permit one to enunciate the rules of architecture for tissue engineering of bone
      and cartilage. The purification and cloning of bone morphogenetic proteins (BMPs)
      and growth factors such as platelet derived growth factors (PDGF), transforming
      growth factor-beta (TGF-beta), and insulin-like growth factors (IGF-I) will allow
      the design of an optimal combination of signals to initiate and promote
      development of skeletal stem cells into cartilage and bone. Successful and
      optimal bone and cartilage formation is a synergy of inductive and conductive
      strategies governed by biomechanics, optimal load bearing, and motion. BMPs
      function as inductive signals. Biomaterials (both natural and synthetic) mimic
      the extracellular matrix and play a role in conduction of bone and cartilage.
      Examples of biomaterials include hydroxyapatite, polyanhydrides,
      polyphosphoesters, polylactic acid, and polyglycolic acid. The prospects for
      novel biomaterials are immense, and they likely will be a fertile growth
      industry. Cooperative ventures between academia and industry and technology
      transfer from the federal government augur well for an exciting future for
      clinical applications.

PMID- 7829581
TI  - Recent progress in immunoisolated cell therapy.
AB  - Biohybrid implants represent a new class of medical device in which living cells,
      supported in a hydrogel matrix, and surrounded by a semipermiable membrane,
      produce and deliver therapeutic reagents to specific sites within a host. First
      proposed in the mid-1970s for diabetes, this treatment modality has progressed
      rapidly in the past four years and is now being investigated not just for
      endocrine disorders but also for alleviation of chronic pain, treatment of
      neurodegenerative disorders, and delivery of neurotrophic factors to sites within
      the blood brain barrier, and as a practical alternative to conventional ex vivo.

PMID- 7829582
TI  - Tissue engineering a blood vessel: regulation of vascular biology by mechanical
      stresses.
AB  - Important to the tissue engineering of a substitute blood vessel is an
      understanding of those factors which regulate vascular biology. A major factor in
      this regulation is the mechanical environment imposed by the hemodynamics of the
      vascular system. In this the vascular endothelium plays a critical role, and over
      the past two decades much has been learned about the influence of hemodynamics on
      vascular endothelial biology, to a large degree using cell culture to study the
      effects of flow and cyclic stretch. In our laboratory, such studies are now being
      extended through the development of a model of the arterial wall involving the co
      culture of endothelial cells and smooth muscle cells. The development of such a
      model and its use in the study of hemodynamic effects represents necessary steps
      in the evolution of approaches to tissue engineering a blood vessel.

PMID- 7829583
TI  - Prospects for application of biotechnology-derived biomaterials.

PMID- 7829584
TI  - Influence of polysaccharides on neutrophil function: specific antagonists suggest
      a model for cooperative saccharide-associated inhibition of immune complex
      triggered superoxide production.
AB  - We have previously shown that certain monosaccharides (N-acetyl-D-glucosamine and
      mannose) could cooperatively inhibit the ability of neutrophils to release
      superoxide anions in response to immune complexes. To test the possible origins
      of the cooperative inhibition of superoxide release, we have examined the effect
      of a panel of polysaccharides on superoxide release in the presence or absence of
      immune complexes. Although exposure to particulate beta-glucan and hyaluronan
      triggered superoxide release from neutrophils, other polysaccharides including
      chitin and mannan were without effect. Both chitin and mannan, but not other
      polysaccharides, inhibited the immune complex-mediated stimulation of superoxide
      release in a dose-dependent fashion. In sharp contrast to the cooperative
      inhibition mediated by monosaccharides, chitin and mannan exhibited Hill
      coefficients of 1. This inhibition of superoxide production was not due to simple
      blockage of Fc receptors since fluorescent immune complexes bound equally well to
      neutrophils in the presence or absence of mannan or chitin as shown by
      epifluorescence microscopy and quantitative fluorometry. Furthermore, this
      inhibition of superoxide release was not observed when neutrophils were
      stimulated with phorbol myristate acetate and ionophore A23187 or hyaluronan.
      Therefore, the specific inhibition of superoxide production by mannan and chitin
      could not be explained by either receptor blockage or by some nonspecific effect
      on cells. We suggest that these molecules interfere with a step in transmembrane
      signaling, presumably involving the integrin CR3. The observed Hill coefficients
      suggest the possibility that one polysaccharide may simultaneously bind to two
      monosaccharide binding sites yielding a Hill coefficient of 1, whereas individual
      monosaccharides separately bind yielding a Hill coefficient of 2.

PMID- 7829585
TI  - Oscillatory behavior of control-systems of calcium homeostasis in chickens.
AB  - Computer simulation of calcium homeostasis in chicks predicted an oscillatory
      behavior of bone calcium flow and kidney 25-hydroxyvitamin D3-1-hydroxylase with
      a periodicity of 56 h and a 9 h phase difference between the two signals. In
      growing chickens subjected to a light: dark cycle of 22:2 h, and intravenously
      dosed with 45Ca, the temporal changes in plasma 45Ca could be described by an
      exponential decline with superimposed diurnal oscillations. The activity of the
      renal 25-hydroxyvitamin D3-1-hydroxylase in chicks subjected to a 12:12 h light:
      dark cycle ALSO followed diurnal oscillations, with a nadir at the beginning of
      the light period and a peak 12 h later. The production of 1,25-dihydroxyvitamin
      D3 by primary cultures of chicken kidney cells oscillated with a periodicity of
      5.6 h or shorter. It is suggested that despite the differences in phase and
      periodicity between the simulation predictions and actual results, the
      oscillations in both 1-hydroxylase and bone calcium flow could be coupled through
      the hormonal systems involved in regulation of plasma calcium.

PMID- 7829586
TI  - Negative regulatory element in the mammary specific whey acidic protein promoter.
AB  - Expression of the whey acidic protein (WAP) gene is tightly regulated in a tissue
      and developmental stage specific manner, in that the WAP gene is exclusively
      expressed in the mammary gland during pregnancy and lactation. Using both
      deletion and competition analyses, evidence is provided for the existence of a
      negative regulatory element (NRE) in the WAP promoter located between -413 and 
      93 with respect to the WAP transcriptional initiation site. This NRE dramatically
      decreases transcription from linked heterologous promoter-reporter gene
      constructs. The activity of NRE requires WAP promoter sequences that are 230 bp
      apart since subfragments of the NRE fail to inhibit transcription of adjoining
      reporter genes. Nuclear extracts from different cell types, in which the WAP gene
      is not active, contain a protein or complex that specifically interacts with the
      entire NRE but not with subfragments of it. The contact points between this
      protein (NRE binding factor [NBF]) and the NRE element have been partially
      determined. Mutation of the implicated nucleotides severely reduces the ability
      of NBF to bind, and such mutated promoter fragments fail to alleviate
      transcriptional repression in competition experiments. This suggests that NBF
      binding to the NRE is at least in part responsible for the negative regulation of
      the WAP promoter. Since NBF is not detectable in the lactating mammary gland,
      where the WAP gene is expressed, we speculate that it may be a determinant of the
      expression spectrum of the WAP gene.

PMID- 7829587
TI  - Expression of cell growth and bone phenotypic genes during the cell cycle of
      normal diploid osteoblasts and osteosarcoma cells.
AB  - Establishing regulatory mechanisms that mediate proliferation of osteoblasts
      while restricting expression of genes associated with mature bone cell phenotypic
      properties to post-proliferative cells is fundamental to understanding skeletal
      development. To gain insight into relationships between growth control and the
      developmental expression of genes during osteoblast differentiation, we have
      examined expression of three classes of genes during the cell cycle of normal
      diploid rat calvarial-derived osteoblasts and rat osteosarcoma cells (ROS
      17/2.8): cell cycle and growth-related genes (e.g., histone), genes that encode
      major structural proteins (e.g., actin and vimentin), and genes related to the
      biosynthesis, organization, and mineralization of the bone extracellular matrix
      (e.g., alkaline phosphatase, collagen I, osteocalcin, and osteopontin). In normal
      diploid osteoblasts as well as in osteosarcoma cells we found that histone genes,
      required for cell progression, are selectively expressed during S phase. All
      other genes studied were constitutively expressed both at the transcriptional and
      posttranscriptional levels. Alkaline phosphatase, an integral membrane protein in
      both osteoblasts and osteosarcoma cells, exhibited only minimal changes in
      activity during the osteoblast and osteosarcoma cell cycles. Our findings clearly
      indicate that despite the loss of normal proliferation-differentiation
      interrelationships in osteosarcoma cells, cell cycle regulation or constitutive
      expression of growth and phenotypic genes is maintained.

PMID- 7829588
TI  - Reference preparations in the standardisation of HIV-1 PCR--an international
      collaborative study.
AB  - Following the recent developments in diagnostic polymerase chain reaction (PCR)
      technology, we have assessed a set of HIV-1 DNA reference standards using the
      first commercial diagnostic test kit for the detection of HIV-1 (Amplicor, Roche)
      in an international collaborative study. Nineteen laboratories in 11 countries
      analysed a set of ten (re-coded) HIV-1 DNA reference standards, whose performance
      had been validated in a previous collaborative study (Bootman and Kitchin, 1992).
      Results from the current study show that, using the diagnostic kit, 84% of
      laboratories (16/19) obtained correct diagnoses for all ten test samples. One
      additional laboratory failed only to detect the sample containing ten copies of
      target template. Test results from the remaining two laboratories were declared
      void in accordance with the Amplicor quality control guidelines.

PMID- 7829589
TI  - Detection of immunoglobulin G to measles virus, rubella virus, and mumps virus in
      serum samples and in microquantities of whole blood dried on filter paper.
AB  - Immunity to measles virus, rubella virus, and mumps virus was determined by EIA
      in serum samples and in dried whole blood specimens spotted on Whatman filter
      paper (5 mm in diameter). Both specimens were obtained from each patient by
      venepuncture and finger prick. Ten microliters of whole blood is enough to detect
      antibodies to these three different viruses. The comparison of the results
      obtained by EIA from 227 serum and whole blood samples have demonstrated close
      agreement: 98.6% for measles virus, 99.1% for rubella virus, and 96.0% for mumps
      virus. Moreover, 96 whole blood samples can be tested in a microtiter plate and
      can be stored at room temperature for 15 days or at +4 degrees C for several
      months. Therefore, whole blood dried on filter paper is a convenient alternative
      method for collecting and transporting specimens, it is easier and safer than
      venepuncture, and could be used for large-scale epidemiological studies,
      especially in newborns. This method could solve the problem of sampling,
      especially in young children, and could simplify studies of vaccine efficacy.

PMID- 7829590
TI  - Enhanced diagnostic efficiency of the polymerase chain reaction by co
      amplification of multiple regions of HIV-1 and HIV-2.
AB  - A method for co-amplification of multiple viral sequences of HIV-1 and HIV-2 by
      polymerase chain reaction was designed. The technique resulted in the specific
      detection of each type of virus and allowed the amplification of as few as two
      copies of target DNA. The amplification of multiple regions of the viral genome
      offers the advantage of detecting multiple target sequences, which may be
      essential for some viruses, such as HIV, that exhibit a high degree of
      variability in their gene sequences. In addition, the method permitted the
      detection of both virus types in the same reaction, allowing for greater utility
      in geographic areas where coinfections with both viruses occur and cross
      reactivity in Western blots is observed. This method was applied successfully to
      the detection of viral DNA in clinical specimens.

PMID- 7829591
TI  - Sensitive detection of Ross River virus--a one-tube nested RT-PCR.
AB  - A sensitive nested RT-PCR that can be carried out in a single tube is described.
      The sensitivity of this system was determined, and compared to that of a single
      round of PCR, and a single round of PCR followed by hybridisation with a
      radiolabelled oligonucleotide probe. We found that with the one-tube nested RT
      PCR we were able to detect 0.1 pfu/ml of Ross River virus. The nested RT-PCR was
      100-times more sensitive than a single round of RT-PCR followed by hybridisation,
      and 10,000-times more sensitive than a single round of RT-PCR alone. This system
      provides a sensitive detection of Ross River virus, and can be adapted for
      detection of RNA from any source. The test material is added to a single tube at
      the outset, and by subsequent addition of two sets of reagents, the entire nested
      RT-PCR can be carried out in the same tube. This system has maximum sensitivity,
      minimises risk of contamination, and is amenable to automation.

PMID- 7829592
TI  - Rapid detection of active cytomegalovirus infection by in situ polymerase chain
      reaction on MRC5 cells inoculated with blood specimens.
AB  - An in situ polymerase chain reaction was developed to amplify immediate early
      genes of human cytomegalovirus in cells cultured in a 96 well plate and infected
      with leukocytes. The technical parameters enabling optimal detection of the DNA
      sequences were defined. The key to this method is the fixation of cells, which
      facilitates the access of the PCR mixture into the cell nuclei and preserves cell
      morphology. Such a technique could have wide application for the detection and
      identification of other infectious viruses in cultured cells very early after
      inoculation of clinical samples.

PMID- 7829593
TI  - A rapid indirect ELISA for the serogrouping of Australian orbiviruses.
AB  - This communication describes the development and evaluation of a simple and rapid
      method for the classification of Australian orbiviruses into one of seven
      established serogroups (i.e. bluetongue, epizootic haemorrhagic disease of deer,
      Palyam, Eubenangee, Corriparta, Wallal, Warrego) or an 'ungrouped' category. The
      Australian orbivirus serogrouping ELISA (SG-ELISA) utilised a sodium deoxycholate
      treated cell lysate preparation from infected BHK cells which was subsequently
      probed in an indirect ELISA format with polyclonal antibodies representative of
      each serogroup. Bound immunoglobulin was detected by the use of a recombinant
      streptococcal protein G-HRPO conjugate and subsequent reaction with the
      chromogenic substrate. All reference orbiviruses tested in the SG-ELISA were
      identified and were in agreement with the serogroups originally designated.
      Minimal inter-serogroup cross-reactions were observed. One-way cross-reactions
      were observed between Warrego and Mitchell River viruses.

PMID- 7829594
TI  - Improvement of hepatitis C virus RNA polymerase chain reaction through a
      multicentre quality control study. French Study Group for the Standardization of
      Hepatitis C Virus PCR.
AB  - Nine French laboratories, using the polymerase chain reaction (PCR) for detection
      of hepatitis C virus (HCV) RNA, initiated a quality control study to assess and
      to improve the specificity and sensitivity of their procedures. The study was
      carried out in three rounds, based on coded panels consisting of anti-HCV
      positive and anti-HCV negative samples. For the first panel, each laboratory
      followed its own protocol: 100% sensitivity was observed in two laboratories,
      100% specificity in seven. For the second panel, all laboratories were required
      to use both their own procedure and a consensus procedure established from those
      laboratories which provided the best results on the first panel. With their own
      procedure, 100% sensitivity was observed in five laboratories and 100%
      specificity in all. With the common procedure, 100% sensitivity was observed in
      all but one, and 100% specificity in all. The third panel included three positive
      samples with four successive dilutions. For two samples, 8/8 laboratories had
      positive signals until the 1/100 dilution and discrepant results beyond this
      dilution; for the third sample, the signals were more discrepant. These results
      indicate that optimization and standardization of PCR may help laboratories to
      improve their procedure.

PMID- 7829595
TI  - A competitive avidin-biotin ECL dot-blot assay for epitope mapping of monoclonal
      antibodies.
AB  - Using antigen-soaked nitrocellulose sheets stamped to Teraski plates, a
      microtechnique was devised for detecting bound biotinylated monoclonal antibodies
      which readily demonstrated non-overlapping epitopes. This procedure is simple,
      sensitive and rapid and is useful in screening hybridoma supernatants.

PMID- 7829596
TI  - Quantitative and discriminative detection of individual HIV-1 mRNA subspecies by
      an RNAse mapping assay.
AB  - HIV-1 genes are expressed through the complex splicing of a single mRNA precursor
      leading to three mRNA classes: unspliced, singly-spliced and multiply-spliced.
      Each class may include several mRNA species specifically encoding one or two HIV
      1 proteins. Northern blotting and RT-PCR are the techniques currently used to
      analyse HIV-1 mRNA expression. Northern blotting allows quantitative detection of
      these three classes of viral RNA but does not discriminate between individual RNA
      species. RT-PCR allows discrimination between different species but does not
      provide a quantitative analysis. Here, we describe an application of an RNAse
      mapping assay which gives both quantitative and discriminative HIV-1 RNA
      detection. A radiolabeled probe overlapping the major splicing sites of HIV-1
      used for the generation of HIV-1 mRNA subspecies was synthesized. This probe
      protects differential sizes of these species, allowing discrimination between
      them. We investigated the RNA expression pattern in high titer HIV-1 producing
      cells. The HIV-1-specific probe allowed the detection of multiply-spliced vpr,
      rev and nef mRNAs, singly-spliced env mRNA and unspliced genomic RNA. With its
      discriminative and quantitative properties, this application is particularly
      convenient for the investigation of HIV-1 mRNA expression during the course of
      HIV-1 infections.

PMID- 7829597
TI  - Simplified sample preparation for detection of wheat streak mosaic virus and
      barley yellow dwarf virus by PCR.
AB  - A PCR diagnostic procedure for wheat streak mosaic virus (WSMV) was developed
      using a primer derived from 3'-terminal sequences of five WSMV isolates and an
      oligo d(T)-based primer. Cereal extracts prepared by digestion with proteinase K
      and boiling permitted PCR-based detection of both WSMV and BYDV in field samples.
      This procedure saves time, eliminates multiple liquid transfer steps, and reduces
      the chances of cross contamination. Sensitivity of such assays is still very
      good; BYDV could be readily detected in plant sap diluted over 1000-fold.
      Further, parallel detection of WSMV and barley yellow dwarf virus (BYDV) in the
      same samples is possible with this method.

PMID- 7829598
TI  - Hypothyroidism-induced macroorchidism: use of a gonadotropin-releasing hormone
      agonist to understand its mechanism and augment adult stature.

PMID- 7829599
TI  - Linkage of familial dysalbuminemic hyperthyroxinemia to the albumin gene in a
      large Amish kindred.
AB  - Familial dysalbuminemic hyperthyroxinemia (FDH) is the most common cause of
      inherited euthyroid hyperthyroxinemia in Caucasians. Transmitted as an autosomal
      dominant trait, it is always associated with high serum total T4 (TT4) and more
      rarely with elevated total T3 (TT3) and/or rT3 (TrT3) concentrations. Free T4, by
      dialysis, and TSH levels are normal, suggesting the presence of a T4-binding
      protein abnormality. The abnormal serum T4 carrier shares some physical and
      immunological properties with albumin, suggesting that it may be albumin itself.
      Here we show linkage between FDH and the albumin gene in a large Amish family of
      Swiss descent, using as markers a SacI polymorphism in the coding sequence of the
      albumin gene and the group-specific component (Gc) gene, located less than 1
      centimorgan from the albumin gene. Blood samples were obtained from 160 members
      of this kindred, and 22 had FDH identified by the pattern of T4 binding to serum
      proteins separated by isoelectric focusing. Serum TT4 values were above the
      normal range in all subjects expressing the FDH phenotype, and TrT3 levels were
      above the normal range in only one half. TT4 concentrations correlated positively
      with TrT3 and TT3. All TT3 values were, however, within the normal range. Free T4
      and TSH levels were normal, confirming the euthyroid state in these subjects. FDH
      was associated with the albumin SacI(+)/Gc 1S haplotype, yielding a LOD
      (logarithm of the odds ratio) score of 5.53, with a recombination frequency of 0.
      These data provide strong support that a variant albumin is the cause of FDH in
      this kindred.

PMID- 7829600
TI  - Effects of recombinant human growth hormone (GH) on bone and intermediary
      metabolism in patients receiving chronic glucocorticoid treatment with suppressed
      endogenous GH response to GH-releasing hormone.
AB  - Glucocorticoids, when administered over prolonged periods of time, cause protein
      wasting, osteoporosis, elevation of total cholesterol, and carbohydrate
      intolerance. Human GH is a potent anabolic agent known to stimulate protein
      synthesis and osteoblast activity. Chronic hypercortisolemia is associated with
      impaired GH secretion. The aim of our study was to evaluate the effects of short
      term administration of human recombinant GH on bone and fuel metabolism in
      patients receiving chronic glucocorticoid treatment and with suppressed GHRH
      stimulated GH peaks (< 10 micrograms/L). We studied nine nonobese adult patients
      more than 70 yr of age (seven females and two males; age range, 41-68 yr; body
      mass index, 26 +/- 1.3 kg/m2) undergoing long term glucocorticoid therapy for
      nonendocrine diseases. After a 3-day stabilization period in the hospital,
      several parameters were evaluated in all patients: 1) protein, 2) bone, 3) lipid,
      4) carbohydrate metabolism, and 5) immune system function under baseline
      conditions. At 1800 h on the fifth day of hospitalization, the patients began
      treatment with a daily sc injection of 0.1 IU/kg (0.037 mg/kg) recombinant human
      GH (Humatrope, Eli Lilly Co.) for 7 days. GH administration caused a significant
      increase in nitrogen balance (from -0.12 +/- 0.04 to -0.03 +/- 0.02 g/kg.day; P <
      0.05), osteocalcin, carboxy-terminal propeptide of type I procollagen, and
      carboxy-terminal telopeptide of type I collagen with respect to basal levels.
      After GH administration, total, high density lipoprotein, and low density
      lipoprotein cholesterol levels were significantly lowered, and serum triglyceride
      levels were increased in all patients. Normal blood glucose levels during GH
      administration were observed in our patients concomitantly with a slight increase
      in insulin secretion. After GH treatment, the T-helper/T-suppressor cell ratio
      significantly increased with respect to basal levels (2.5 +/- 0.4 vs. 2.2 +/-
      0.3; P < 0.05). Our data suggest that in patients receiving chronic
      glucocorticoid treatment, GH administration may significantly antagonize several
      side-effects of long term glucocorticoid administration, such as protein wasting,
      osteoporosis, and hyperlipidemia.

PMID- 7829601
TI  - Relaxin gene expression in human reproductive tissues by in situ hybridization.
AB  - The expression of the two human relaxin genes termed H1 and H2 in human
      reproductive tissues ranges from high to very low copy number depending upon the
      tissue and reproductive state. The aim of this study was to use two approaches to
      identify total relaxin transcripts (HI and H2) at the cellular level by using a
      human relaxin H2 riboprobe and a series of six 48-mer synthetic oligoprobes. The
      results obtained with both methods were similar in all tissues studied; however,
      a lower background was achieved with the riboprobe. This was especially
      noticeable after long exposure times, and a better resolution was generally
      achieved without clustering of the signals. Treatment of the tissues with
      proteinase-K failed to increase the sensitivity in any tissue with either probe.
      The relative levels of expression of the total relaxin gene transcripts was
      estimated from the different exposure times needed to obtain a good hybridization
      signal. Thus, the order of expression was: corpus luteum of pregnancy > corpus
      luteum of the cycle > placenta and prostate > decidua parietalis. The results
      agree well with immunolocalization of the peptide hormone previously performed
      with both heterologous and homologous relaxin antibodies; the exception was the
      lack of hybridization signal over the cells of the chorionic cytotrophoblast of
      the chorion laeve. This suggests that the levels of relaxin gene expression was
      below the level of detectability with the in situ hybridization technique or that
      these cells sequester, but do not synthesize, relaxin. Expression in the term
      placenta varied greatly from tissue to tissue and within any one tissue. A
      similar variability has been noted for relaxin in this tissue by
      immunocytochemistry. Methodology for the detection of total relaxin transcripts
      at the cellular level when expressed in a wide range of copy number will allow
      the developmental regulation of relaxin gene expression in reproductive and
      nonreproductive tissues to be visualized.

PMID- 7829602
TI  - Expression of messenger ribonucleic acid for epidermal growth factor (EGF),
      transforming growth factor-alpha (TGF alpha), and EGF receptor in human amnion
      cells: possible role of TGF alpha in prostaglandin E2 synthesis and cell
      proliferation.
AB  - The amnion plays important structural and functional roles in the maintenance of
      pregnancy and the initiation of parturition. Recently, we reported that epidermal
      growth factor (EGF) activates prostaglandin (PG) production and cell growth in
      cultured amnion cells. In this study, we showed the expression of EGF,
      transforming growth factor-alpha (TGF alpha), and EGF receptor protein and
      messenger ribonucleic acid in amnion cells, using an immunofluorescence technique
      and the reverse transcription-polymerase chain reaction. Next, we studied the
      effect of TGF alpha on intracellular Ca2+ mobilization and PGE2 production in
      amnion cells. TGF alpha induced an increase in the intracellular Ca2+
      concentration in amnion cells, and this increase was significantly reduced when
      the cells were incubated with cobalt chloride (a Ca2+ channel blocker; 2.5
      mmol/L) or EGTA (a Ca2+ chelator; 5 mmol/L). TGF alpha enhanced PGE2 production,
      and this increase was significantly inhibited when the cells were incubated with
      indomethacin (a cyclooxygenase inhibitor; 10 mumol/L), cobalt chloride (2.5
      mmol/L), or EGTA (5 mmol/L). We also investigated the effect of TGF alpha on the
      growth of cultured human amnion cells by using flow cytometric analysis of the
      DNA content. TGF alpha induced DNA synthesis by human amnion cells, and
      indomethacin inhibited the TGF alpha-induced DNA synthesis. These results suggest
      that 1) EGF/TGF alpha are expressed and produced in amnion cells; 2) these
      endogenous factors may regulate the proliferation of amnion cells in an autocrine
      or paracrine manner; and 3) these growth factors may exert their effects via
      intracellular Ca2+ mobilization and PGE2 production.

PMID- 7829603
TI  - Human pituitary adenomas express endogenous inhibin subunit and follistatin
      messenger ribonucleic acids.
AB  - Specific factors involved in the pathogenesis of tumors that stimulate clonal
      human pituitary adenoma cell proliferation remain unknown. An important question
      regarding the pathogenesis of human pituitary tumors is whether they synthesize
      autocrine regulatory factors that regulate both hormone biosynthesis and
      neoplastic growth. Activin and inhibin are both comprised of inhibin subunits and
      have diverse regulatory roles as growth and differentiation factors in normal and
      neoplastic tissue. Activin stimulates FSH beta messenger ribonucleic acid (mRNA)
      biosynthesis and FSH secretion, and these effects are down-regulated in normal
      gonadotrophs by the endogenous glycoprotein follistatin. In addition to its
      effects on gonadotrophs, activin modulates hormone secretion by somatotroph and
      corticotroph cell lines. It is not known whether human neoplastic pituitary
      tissue synthesizes inhibin subunits or follistatin or whether their expression is
      cell type specific. We investigated whether alpha-, beta A-, and beta B-inhibin
      subunit and follistatin mRNAs could be detected in 27 human pituitary adenomas
      [clinically nonfunctioning (n = 11), somatotroph (n = 5), corticotroph (n = 5),
      and lactotroph (n = 6)] using reverse transcriptase-polymerase chain reaction
      techniques. Twenty-six of the tumors contained mRNAs encoding one or more inhibin
      subunits. beta B-Inhibin mRNA was the most prevalent (81% of tumors), followed by
      beta A-inhibin (59% of tumors) and alpha-inhibin (52% of tumors). Endogenous
      alpha-, beta A-, and beta B-inhibin subunit mRNA synthesis was also examined in
      normal human pituitary and testicular complementary DNA libraries, and all
      subunit mRNAs were detected. In contrast to the widespread expression of inhibin
      subunits in pituitary tumors, follistatin mRNA was detected in a subset of
      nonfunctioning tumors (54%) as well as in control normal human pituitary and
      testicular complementary DNA libraries. Tumor-specific follistatin biosynthesis
      was not observed in other pituitary tumor subtypes. These data are the first to
      demonstrate that 1) endogenous inhibin subunits are synthesized in human
      pituitary adenomas of all known secretory phenotypes as well as normal pituitary
      tissue; and 2) follistatin gene expression in pituitary adenomas is specific to
      clinically nonfunctioning or gonadotropin subunit-producing tumors. The
      characterization of inhibin subunit and follistatin biosynthesis by human
      pituitary tumors will be important in investigating their potential roles in
      regulating both tumor phenotype and cell proliferation.

PMID- 7829604
TI  - The effect of low dose recombinant human growth hormone replacement on regional
      fat distribution, insulin sensitivity, and cardiovascular risk factors in
      hypopituitary adults.
AB  - GH deficiency is associated with increased cardiovascular morbidity, which may be
      determined by alterations in vascular risk factors. We report the effect of
      partially treated hypopituitarism and subsequent GH replacement (mean dose, 0.2
      IU/kg.week) on putative cardiovascular risk factors in 22 nondiabetic
      hypopituitary subjects in a 6-month, double blind, controlled study
      (active/placebo ratio, 11:11). All patients were subsequently treated with GH for
      a further 6 months. Total fat, percent body fat, and central fat were measured by
      dual energy x-ray absorptiometry. The hypopituitary patients had increased
      percent fat (P = 0.03) and central fat (P < 0.01) compared with body mass index
      matched controls. Before GH treatment, fasting (total) and specific insulin
      positively correlated with body mass index (P = 0.02 and P < 0.001,
      respectively), waist/hip ratio (P = 0.05 and P = 0.01), and central fat (P = 0.03
      and P = 0.003). Specific insulin and insulin sensitivity (IS), calculated by
      homeostatic model of assessment, were related to total fat (P < 0.001 and P =
      0.02). GH treatment for 6 months led to a reduction in total fat (P < 0.02),
      percent fat (P = 0.002), central fat (P = 0.012), waist/hip ratio (P < 0.05),
      total cholesterol (P = 0.03), and apolipoprotein-B (P = 00001), as well as a
      decrease in the IS from 36.9% (range, 12-100%) to 25% (range, 2.5-55%; P =
      0.0002). This was paralleled by a rise in fasting (total) and specific insulin (P
      = 0.016 and P = 0.002). The degree of correlation among indices of IS, body
      composition, and fat distribution increased after GH treatment. Fasting plasma
      glucose rose significantly, but was within the reference range. During 12 months
      of GH therapy, a significant increase in serum lipoprotein-(a) was observed (P <
      0.05). Although GH has beneficial effects on central adiposity and lipid
      fractions, it is also associated with a decrease in IS; these effects may vary
      between individuals.

PMID- 7829605
TI  - Regulation of production and secretion of sex hormone-binding globulin in HepG2
      cell cultures by hormones and growth factors.
AB  - Regulation of the production and secretion of sex hormone-binding globulin (SHBG)
      was investigated in HepG2 cell cultures by measuring SHBG protein concentrations
      intra- and extracellularly and studying changes in SHBG messenger ribonucleic
      acid levels. Insulin (10 nmol/L), insulin-like growth factor-I (15 nmol/L), and
      epidermal growth factor (20 nmol/L) decreased SHBG levels in parallel both intra-
      and extracellularly. Ten nmol/L 17 beta-estradiol, 10 nmol/L testosterone, and
      100 nmol/L to 1 mumol/L cortisol increased SHBG levels inside the cells, but did
      not increase its release into the culture medium. Two hundred and fifty to 500
      nmol/L 17 beta-estradiol and 500 nmol/L to 1 mumol/L testosterone increased SHBG
      levels intra- and extracelularly, but relative to control values, the increase
      was considerably greater inside the cells. T3 (10 nmol/L) increased SHBG levels,
      but unlike the effect seen with steroids, the increase was equally evident within
      the cells and the medium. Northern hybridization showed that insulin decreased
      and 17 beta-estradiol and T3 increased SHBG messenger ribonucleic acid levels
      marginally. The variable secretion of SHBG is hypothesized to be due to the
      different effects of hormones and growth factors on either the glycan moiety of
      SHBG or the expression of the alternatively spliced transcripts of the SHBG gene.

PMID- 7829606
TI  - The long-term outcome after adrenalectomy and prophylactic pituitary radiotherapy
      in adrenocorticotropin-dependent Cushing's syndrome.
AB  - We have reviewed our experience of adrenalectomy performed as part of the
      management of 56 patients with ACTH-dependent Cushing's syndrome between 1946 and
      1993. Forty-three patients were operated on at our institution. Surgery-related
      mortality did not occur, but complications developed in 14 (33%); these were
      minor in 12. Eleven patients (29%) of the 38 for whom long-term follow-up data
      were available and who did not have a proven ectopic source of ACTH subsequently
      developed Nelson's syndrome, diagnosed on the basis of clinical pigmentation and
      markedly elevated ACTH levels that were not normally suppressible with
      glucocorticoids. The effects of prophylactic pituitary radiotherapy were assessed
      in 38 patients who underwent adrenalectomy at our institution and 18 who
      underwent surgery elsewhere. Patients who had received prophylactic radiotherapy
      were less likely to develop Nelson's syndrome (5 of 20, 25%) compared to those
      who did not (18 of 36, 50%; P > 0.07), and there was a low incidence of
      radiotherapy-induced hypopituitarism. We conclude that total adrenalectomy has
      proved to be a safe and effective operation and still may be indicated in
      selected patients with ACTH-dependent Cushing's syndrome; because prophylactic
      pituitary radiotherapy reduces the incidence of subsequent Nelson's syndrome by
      50%, it should always be considered in the management of these patients.

PMID- 7829607
TI  - Sometimes the hooves do belong to zebras! An unusual case of hypopituitarism.

PMID- 7829608
TI  - Gender and Tanner stage differences in body composition and insulin sensitivity
      in early pubertal children.
AB  - A cross-sectional analysis examining the impact of gender and early pubertal
      stage on insulin sensitivity (Si) and body composition was carried out as part of
      a longitudinal study to determine how Si relates to body composition changes
      during puberty. The study population consisted of 97 healthy children (age range,
      9.7-14.5 yr; 28 Tanner stage 2 boys, 25 stage 3 boys, 22 Tanner stage 2 girls,
      and 22 stage 3 girls). Si was determined by the modified minimal model of
      Bergman. Body fatness was assessed by body mass index (BMI), skinfold thickness,
      hydrodensitometry, and bioelectrical impedance. Results showed that stage 3 girls
      and stage 2 boys had significantly more body fat than stage 2 girls and stage 3
      boys. Si was significantly lower (P < 0.02) and insulin-like growth factor-I
      levels higher (P < 0.006) in stage 3 girls compared to those in the other 3
      groups. The best predictor of Si in all subjects was BMI (r2 = -0.63; P <
      0.0001). In a stepwise multiple regression analysis, Si was best predicted from
      BMI, gender, and Tanner stage. According to this model, Si decreased as BMI
      increased and was lower in girls and Tanner stage 3 children. In boys, Si was
      best predicted from total fat mass and Tanner stage. In girls, Si correlated
      inversely with BMI, parental obesity, and insulin-like growth factor-I levels.
      Neither testosterone nor estradiol levels were associated with Si. These results
      demonstrate that Si, like body composition, has gender-dependent changes during
      puberty. It is, thus, possible that these pubertal changes in Si relate to
      changes in body composition.

PMID- 7829609
TI  - Adrenocorticotropin hyperresponse to the corticotropin-releasing hormone-mediated
      stimulus of naloxone in patients with myotonic dystrophy.
AB  - We previously showed that CRH-mediated stimuli, including exogenous CRH, cause
      ACTH hypersecretion in many myotonic dystrophy (DM) patients. We confirmed this
      by giving naloxone, a stimulator of endogenous CRH release, to a large number of
      DM patients and controls. DM patients, first degree relatives, and normal
      controls received i.v. naloxone at 1400 h, and blood was taken for ACTH (RIA) and
      cortisol (high pressure liquid chromatography) measurements from 15 min before to
      120 min after naloxone treatment. DM patients had basal ACTH levels approximately
      twice those of controls, and their ACTH responses were 4 times those of controls.
      In contrast, DM basal cortisol levels were not significantly different from those
      of relatives and were slightly higher than those of normal subjects. Cortisol
      responses were similar in the three groups, probably due to attenuation at high
      levels of adrenocortical stimulation, although some patients with inappropriately
      low cortisol responses for their level of ACTH stimulation warrant further
      investigation. Nineteen of the 36 patients whose ACTH responses were greater than
      3 SD above the normal mean were classed as hyperresponders. Seven patients, who
      were tested more than once, had reproducible responses relative to those of the
      normal subjects. We conclude that ACTH hypersecretion after CRH-mediated stimuli,
      including naloxone, is an inherent, but variable, feature of DM, caused by
      expression of the genetic mutation at the anterior pituitary. The mechanism is
      probably a defect in the intracellular pathway initiated by CRH-receptor
      interaction as a result of abnormal levels of a cAMP-dependent kinase, DMPK, the
      product of the gene undergoing mutation in DM.

PMID- 7829610
TI  - The corticotropin-releasing hormone (CRH) in normal and tumoral epithelial cells
      of human endometrium.
AB  - CRH is produced by several intrauterine sites, including placenta and desidua,
      during pregnancy. However, no data are available regarding the presence of CRH in
      the nonpregnant uterus. We now report that CRH is produced in the epithelial
      cells of normally cycling human uterus and in an endometrial epithelial cell
      derived tumor. Specifically, we have found that: 1) Northern blot hybridization
      analysis of normal glandular endometrium as well as of Ishikawa human endometrial
      adenocarcinoma cells showed the presence of the CRH messenger RNA; the size of
      the transcript seemed to be identical to that present in human placenta and rat
      hypothalamus; 2) immunoreactive CRH (ir-CRH) was detectable in normal dispersed
      glandular endometrial cells as well as in the Ishikawa adenocarcinoma cells; 3)
      gel filtration chromatography of normal glandular endometrial and Ishikawa cell
      extracts and their culture media showed that most ir-CRH present had the mol wt
      of the authentic CRH peptide; in addition, a larger form of ir-CRH was also
      present in both normal and tumoral endometrial epithelial cell extracts; the
      latter most probably correspondents to CRH precursor molecules; and 4)
      immunofluorescence staining of CRH in normal glandular endometrial and Ishikawa
      cells revealed a cytoplasm rich in granules positive for ir-CRH. Our findings
      suggest that CRH may play an important role in the physiological events taking
      place within the uterine cavity, since CRH seems to be present in nonpregnant as
      well as pregnant uteri. Since CRH is expressed in normal endometrial epithelial
      cells and in an epithelial tumoral cell line, we propose the use of the Ishikawa
      cell line as a convenient model for the in vitro study of endometrial CRH.

PMID- 7829611
TI  - Tumor necrosis factor-alpha and interleukin-1 beta inhibit the synthesis and
      release of renin from human decidual cells.
AB  - Cytokines modulate hormone expression in many cell types, including the
      expression of renin in juxtaglomerular cells. However, the effect of cytokines on
      the expression of renin from extrarenal cells is unknown. In this paper, we have
      examined whether tumor necrosis factor-alpha (TNF alpha) and interleukin-1 beta
      (IL-1 beta) modulate the release of renin from human decidual cells. Continuous
      exposure of primary decidual cell cultures from term pregnancies to TNF alpha and
      IL-1 beta caused dose-dependent inhibition of renin release. The maximal
      inhibitions by TNF alpha and IL-1 beta were 75.5% and 55.2%, respectively, and
      the half-maximal effective doses of TNF alpha and IL-1 beta were 30 and 1.1
      pmol/L, respectively. The decrease in renin release by the cytokines was
      statistically significant on days 2-5 (P > 0.001 at each time) and was
      accompanied by inhibition of renin synthesis and renin messenger ribonucleic acid
      levels. The renin messenger ribonucleic acid levels in cells exposed for 4 days
      to TNF alpha (50 ng/mL) or IL-1 beta (50 pg/mL) were 58.0% and 37.7% less than
      those in control cells, respectively. As decidual macrophages express TNF alpha
      and IL-1 beta, the results of this study strongly suggest a paracrine role for
      cytokines in the regulation of decidual renin expression. The effect of these
      cytokines on renin expression in decidual cells is opposite that in
      juxtaglomerular cells.

PMID- 7829612
TI  - Prenatal diagnosis of congenital lipoid adrenal hyperplasia.
AB  - Congenital lipoid adrenal hyperplasia (lipoid CAH) is a rare genetic disorder of
      adrenal and gonadal steroidogenesis of unknown cause in which cholesterol cannot
      be converted to pregnenolone. As a result, affected individuals can make no
      steroid hormones, so that all affected newborns are phenotypic females,
      irrespective of karyotype. We studied two pregnancies in a family with two
      previously affected children by examining fetal karyotype, genital
      ultrasonography, and amniotic fluid steroid concentrations and by performing ACTH
      tests on family members. Prenatal diagnosis correctly identified both an
      unaffected XX fetus and an affected XY fetus. In the affected pregnancy, amniotic
      fluid concentrations of progesterone and pregnenolone were 30% and 50% of normal,
      respectively, but concentrations of 17 alpha-hydroxypregnenolone, 17 alpha
      hydroxyprogesterone, cortisol, dehydroepiandrosterone, androstenedione, and
      estriol were either extremely low or undetectable, suggesting that these detected
      steroids were donated by maternal steroidogenesis. Fetal cord blood obtained at
      the termination of pregnancy showed very low concentrations of estrogens donated
      by the mother's circulation. Absent fetal steroidogenesis was confirmed by gas
      chromatography and mass spectrometry of both fetal and maternal serum. The
      responses of 10 different steroids to adrenal stimulation with ACTH in the
      obligately heterozygous parents were normal. Thus, unlike the case with other
      forms of CAH, heterozygosity cannot be determined by hormonal responses to
      provocative testing with ACTH. Immunocytochemistry and Western blotting showed
      that the affected placental tissue contained P450scc protein, confirming that
      P450scc is intact in these patients.

PMID- 7829613
TI  - T-cell reactivity to recombinant human thyrotropin receptor extracellular domain
      and thyroglobulin in patients with autoimmune and nonautoimmune thyroid diseases.
AB  - Grave's disease and Hashimoto's thyroiditis are common organ-specific disorders
      characterized by an immune response toward a number of thyroid proteins,
      including TSH receptor (TSHR), thyroid peroxidase, and thyroglobulin (Tg).
      Although considerable progress has been made in understanding and mapping the
      autoantibody response to TSHR, much less is known about recognition of TSHR by
      pathogenic T-cells in human disease. To identify such reactions, we analyzed the
      T-cell proliferative responses of peripheral blood lymphocytes (PBMC) to human
      recombinant TSHR extracellular domain (hrecTSHR-ECD amino acids 19-417) expressed
      in Escherichia coli and to Tg. Forty-two patients with autoimmune thyroid disease
      (AITD), 13 patients with non-AITD, and 20 normal subjects were studied. PBMC from
      40% of patients with AITD and 46% of patients with non-AITD reacted significantly
      to hrecTSHR-ECD. The reactivity to Tg was less than that to TSHR-ECD in both
      groups. Five percent of normal subjects showed a response to hrecTSHR-ECD and
      none to Tg. TSHR-specific T-cell lines were developed in 16 of 26 AITD patients
      and 3 of 10 non-AITD patients. CD8-positive T-cell depletion from PBMC of 8
      patients with AITD by the indirect panning method did not enhance the reactivity
      to hrecTSHR-ECD, except in 1 patient. We conclude that TSHR-specific T-cells are
      present in the circulation of patients with AITD and are presumably involved in
      the pathogenesis of thyroid autoimmunity. The lower, but positive, reactivity to
      hrecTSHR-ECD found in patients with non-AITD was unexpected and may be related to
      lymphocytic infiltrates in the thyroid of 7 of the 11 patients.

PMID- 7829614
TI  - Nocturnal wakefulness inhibits growth hormone (GH)-releasing hormone-induced GH
      secretion.
AB  - Recent studies have suggested that spontaneous release of GH as well as GH
      secretion stimulated by exogenous GHRH are influenced by central nervous
      mechanisms that regulate sleep and wakefulness. Here, the effect of nocturnal
      wakefulness on GH secretion stimulated by i.v. administration of GHRH was
      examined in two experiments in healthy men. On all nights, GHRH (1 microgram/kg
      BW) was injected after the subjects had slept for about 2.5 h to minimize
      interference of endogenous release of GH during early sleep with the response to
      exogenous GHRH. Both experiments included a control condition to assess GH
      secretory responses to GHRH during undisturbed sleep and an experimental
      condition to assess the effect of wakefulness. In the control conditions,
      subjects slept throughout the night, and GHRH was administered 170 min after
      sleep onset. In the experimental condition of Exp I (n = 10), subjects were
      awakened 150 min after sleep onset and stayed awake. GHRH was given 20 min after
      awakening. In the experimental condition of Exp II (n = 8), subjects were
      awakened 30 min after GHRH treatment, which was administered 170 min after sleep
      onset. GHRH administrations during sleep fell into epochs of stage 2 sleep or
      rapid eye movement sleep. GH secretion and sleep characteristics before GHRH
      administrations were comparable for experimental and control conditions of both
      experiments. GH secretory responses were inhibited when the subject was awake at
      the time of GHRH administration compared to GH responses during undisturbed
      sleep. Awakening the subject 30 min after GHRH administration abruptly
      interrupted the initiated GH secretory response. The results demonstrate a
      profound inhibitory effect of nocturnal awakenings on GHRH-induced GH secretion.
      They indicate that the GH secretory response to GHRH is strongly determined by
      central nervous system sleep-wake activity.

PMID- 7829615
TI  - Thyroid adaptation to chronic tetraglycine hydroperiodide water purification
      tablet use.
AB  - Tetraglycine hydroperiodide tablets purify water by liberating 8 mg free
      iodine/tablet. The effects of ingesting four tablets daily for 3 months on
      thyroid size, function, and radioactive iodine uptake were studied prospectively
      in eight healthy volunteers. Serum inorganic iodide increased from 2.7 to
      approximately 100 micrograms/dL. Urinary iodide excretion rose 150-fold from a
      pretreatment mean of 0.276 to 40 mg/day. Radioactive iodine uptake was less than
      2% after 7 days and remained below 2% in all subjects at 90 days. Mean serum T4
      and T3 declined after 7 days. T4 remained below baseline, whereas T3 had
      recovered by the end of the treatment period. Serum TSH and the TSH response to
      TRH rose significantly after 7 days and remained elevated at 3 months. The
      average thyroid volume, determined by ultrasound, increased by 37%. Neither
      hyperthyroidism nor hypothyroidism was observed. The mean thyroid volume in seven
      subjects available for repeat determinations an average of 7.1 months after the
      study was not different from the baseline value. In normal subjects, a reversible
      TSH-dependent thyroid enlargement occurs in response to the iodine load from
      daily use of tetraglycine hydroperiodide water purification tablets.

PMID- 7829616
TI  - Evidence for disturbed regulation of calciotropic hormone metabolism in gitelman
      syndrome.
AB  - Little attention has been paid to interactions between circulating levels of
      calcium, PTH, and 1,25-dihydroxycholecalciferol [1,25(OH)2D] and bone mineral
      density in primary renal magnesium deficiency. Plasma and urinary electrolytes,
      and circulating levels of calciotropic hormones were studied in 13 untreated
      patients with primary renal tubular hypokalemic alkalosis with hypocalciuria and
      magnesium deficiency. The blood ionized calcium concentration was significantly
      lower in patients than in controls. Despite this fact, PTH and 1,25-(OH)2D levels
      were similar in both groups of subjects. The negative linear relationships
      between PTH and ionized calcium, which significantly differed between Gitelman
      patients and healthy subjects in terms of intercept; the negative relationship
      between ionized calcium and 1,25-(OH)2D, which was comparable in both groups; and
      the positive relationship between 1,25-(OH)2D and PTH, which was identical in
      both groups, point both to a blunted secretion of PTH induced by magnesium
      depletion and to the lack of interference of the latter with the activation of 1
      alpha-hydroxylase by PTH. The similar bone mineral density at the lumbar spine by
      dual energy x-ray absorptiometry in 11 patients and 11 healthy subjects argues
      against chronically sustained negative calcium balance.

PMID- 7829617
TI  - Estrogen receptors are present in human granulosa cells.
AB  - Recent studies failed to detect estrogen receptors in primate follicles. This
      study was initiated to determine whether estrogen receptor (ER) messenger
      ribonucleic acid (mRNA) is present in human granulosa cells and, further, if
      functional ER proteins are present. To evaluate the presence of ER, RNA from
      human granulosa cells obtained at the time of oocyte retrieval for assisted
      reproduction was extracted, and complementary DNA synthesis was performed by the
      reverse transcriptase-polymerase chain reaction. Oligonucleotide primers were
      used to amplify basepairs 570-852 in the B- and C- domains of the ER mRNA.
      Southern blotting was performed and confirmed that the amplified DNA fragment
      identified in granulosa cells represented ER. By reverse transcriptase-polymerase
      chain reaction, mRNA for the ER is clearly identified in primary human granulosa
      cells obtained at the time of oocyte retrieval. To expand these studies and
      determine whether functional ER were present in human granulosa cells in culture,
      a simian virus-40-transformed human granulosa cell line was studied. Cells were
      transfected with a plasmid containing as estrogen response element up-stream from
      the bacterial reporter gene chloramphenicol acetyltransferase (CAT). In
      transfected cells, CAT activity is inducible by estradiol if endogenous
      functional ER are present. In these studies, the transfection analysis confirmed
      that functional, transcriptionally competent ER are present in a human granulosa
      cell line, with a 4- to 5-fold enhancement of CAT activity demonstrated after the
      addition of estradiol compared to that in nonhormone-treated cells. In
      conclusion, ER mRNA is present in human granulosa cells. Functional ER are also
      demonstrated in a transformed human granulosa cell line. We hypothesize that low,
      but biologically significant, amounts of ER protein are present in human
      granulosa cells, which are not routinely detectable by standard assays.

PMID- 7829618
TI  - A prospective randomized trial comparing finasteride to spironolactone in the
      treatment of hirsute women.
AB  - Enhanced 5 alpha-reductase activity has been found in the skin of the majority of
      women with hirsutism. Finasteride is a specific competitive inhibitor of 5 alpha
      reductase, preferentially inhibiting the type 2 isoenzyme. Therefore, we randomly
      assigned 14 hirsute women in a 2:1 ratio to 1 of 2 treatment arms: 1) finasteride
      (F) treatment (n = 9; 5 mg, orally, daily), or 2) spironolactone (S) treatment (n
      = 5; 100 mg, orally, daily). Each group was treated for 6 months. Patients were
      evaluated at baseline and after 3 and 6 months of treatment. The 2 groups were
      similar in age, weight, hip/waist ratio, baseline Ferriman-Gallwey score (F, 19
      +/- 2; S, 19 +/- 2), and baseline androgen levels. Finasteride treatment resulted
      in a significant increase in testosterone (T; P < 0.01) and the
      T/dihydrotestosterone ratio (P < 0.01). Finasteride caused a significant decrease
      in 5 alpha-androstane-3 alpha,17 beta-diol glucuronide (3 alpha-diolG; P < 0.05),
      the 3 alpha-diolG/T ratio (P < 0.01), and the 3 alpha-diolG/androstenedione ratio
      (P < 0.05). All changes were consistent with 5 alpha-reductase inhibition. In
      contrast, spironolactone treatment did not result in significant changes in serum
      hormone levels. Both treatments produced a significant decrease in anagen hair
      diameters [F, -14.0 +/- 6.7% (P < 0.05); S, -13.4 +/- 3.8% (P < 0.05)] and
      Ferriman-Gallwey scores [F, -2.1 +/- 0.4 (P < 0.05); S, -2.5 +/- 0.7 (P < 0.05)].
      In conclusion, despite significantly different effects on androgen levels,
      finasteride and spironolactone treatment resulted in a similar clinical effect on
      hirsutism. Both caused significant, but limited, improvement in hirsutism.
      Although promising, further studies with finasteride are needed to verify its
      effectiveness as a treatment for hirsutism. Such studies will also provide a
      better understanding of the relative contribution of 5 alpha-reductase isoenzymes
      to hirsutism.

PMID- 7829619
TI  - Assimilation and mobilization of triglycerides in subcutaneous abdominal and
      femoral adipose tissue in vivo in men: effects of androgens.
AB  - Studies on regional differences of adipose tissue metabolism have mainly been
      performed in vitro. To allow measurements of lipid uptake in vivo in man,
      radioactive label from [9,10-3H]oleic acid in 80 g orally administered milk fat
      was measured after 4 h in abdominal and femoral sc adipose tissues in 28 middle
      aged, abdominally obese men. Radioactivity was measured in adipose tissue
      triglycerides extracted from needle biopsies. Lipoprotein lipase (LPL) activity
      was also measured. Uptake of label in triglycerides and LPL activity were higher
      (20% and 15%, respectively; P < 0.05) in the abdominal compared to the femoral
      adipose tissue region. The men were then randomly assigned to three groups,
      receiving testosterone (T), dihydrotestosterone, or placebo, for 9 months. After
      2 months of treatment, the procedure of administration of label was repeated,
      this time using [U-14C]oleic acid as a marker. Measurements of radioactive label
      was then performed after 4 h and monthly up to 7 months. Supplementation with T
      was followed by an inhibited uptake of label in triglycerides (34%; P < 0.05),
      lower LPL activity (48%; P < 0.05), and a shorter t1/2 (30%; P < 0.05) in the
      abdominal adipose tissue region compared with the dihydrotestosterone and placebo
      groups. No significant effect of T on triglyceride uptake, LPL activity, or t1/2
      was found in sc femoral adipose tissue. It was concluded that the turnover rate
      of depot triglycerides is more rapid in abdominal compared to femoral sc adipose
      tissue in men. Furthermore, T supplementation inhibits triglyceride uptake and
      LPL activity and causes a more rapid turnover of triglycerides only in the sc
      abdominal adipose tissue region. These results demonstrate the marked effects of
      T on adipose tissue metabolism in vivo and suggest that T is an important
      regulator of the proportion of depot fat mass in central and peripheral adipose
      tissue in men.

PMID- 7829620
TI  - Elevated basal adrenocorticotropin and evidence for increased central opioid tone
      in highly trained male athletes.
AB  - Basal cortisol and ACTH levels have previously been shown to be elevated in
      highly trained athletes, whereas the ACTH response to ovine CRH has been reported
      to be diminished compared to that in nonathletic controls. Naloxone, a
      nonselective opioid receptor antagonist, is known to stimulate ACTH and cortisol
      secretion. The mechanism of this response is thought to be via increased
      hypothalamic CRH secretion. The aim of this study was to examine basal and
      naloxone-stimulated levels of hypothalamic-pituitary-adrenal axis hormones in
      male athletes. Ten highly trained male athletes and 10 nonathletic controls took
      part in the study. Peripheral venous blood was sampled for cortisol, ACTH, CRH,
      and arginine vasopressin (AVP) for 2 h before the administration of 20 mg
      naloxone, i.v., and 15, 30, 45, 60, 90, and 120 min after naloxone treatment.
      Body mass index was significantly lower in the athletes (P < 0.001). Basal
      (prenaloxone) ACTH levels were higher in the athletes (P < 0.05), whereas levels
      of cortisol, CRH, and AVP were similar in both groups. After naloxone treatment,
      there was a significantly greater rise in ACTH in the athletes (P < 0.02). There
      was also a trend for the cortisol response to be greater, which was not
      statistically significant (P < 0.07). Although in both groups, peripheral CRH
      rose after naloxone treatment (P < 0.005), a rise of similar magnitude occurred
      over the 2-h period before naloxone (P < 0.0001). Plasma AVP did not change
      significantly after naloxone treatment. Neither the plasma cortisol level at
      baseline nor the body mass index correlated significantly with the ACTH or
      cortisol response to naloxone. The presence of an enhanced ACTH response to
      naloxone is evidence that central opioid tone may be increased in highly trained
      athletes. However, there is no associated suppression of the hypothalamic
      pituitary-adrenal axis, and basal ACTH levels are raised, without any detectable
      change in peripheral plasma CRH or AVP. An additional factor (other than CRH)
      that stimulates ACTH secretion may be released after naloxone administration.

PMID- 7829621
TI  - 17 beta-Estradiol improves postprandial lipid metabolism in postmenopausal women.
AB  - We studied the effect of 2 mg micronized 17 beta-estradiol replacement therapy,
      administered orally during 6 weeks, on postprandial lipid and retinyl palmitate
      (RP) metabolism. In the human postprandial state, atherogenic chylomicron remnant
      particles are produced. RP is incorporated into the core of newly synthesized
      chylomicrons and can be used as a marker of chylomicrons and chylomicron
      remnants. Six normolipidemic (plasma cholesterol, 5.63 +/- 0.83 mmol/L; plasma
      triglycerides, 1.47 +/- 0.69 mmol/L) postmenopausal women (amenorrhea > 1 yr;
      aged 55.5 +/- 4.0 yr) received an oral fat load (50 g/m2 fat as cream, with
      60,000 IU RP/m2) before and after 6 weeks of 17 beta-estradiol treatment. Plasma
      RP areas under the curve decreased significantly from 27.1 +/- 15.9 to 16.6 +/-
      13.2 mg/h.L-1 (P = 0.01). Fasting cholesterol concentrations in intermediate
      density lipoproteins decreased significantly. Fasting and postprandial plasma
      triglyceride levels did not change. These findings indicated that 17 beta
      estradiol improved the postprandial elimination of potentially atherogenic
      lipoprotein remnants.

PMID- 7829622
TI  - Dose-response relationships for radiation-induced hyperparathyroidism.
AB  - It has been hard to establish with certainty that radiation exposure is a risk
      factor for developing hyperparathyroidism. In part this is because many cases of
      hyperparathyroidism remain asymptomatic and escape clinical detection. We present
      results from a study of 2555 subjects who received external beam radiotherapy to
      the head and neck area for benign conditions before their 16th birthday between
      1939 and 1962. The average length of follow-up was 36.6 yr. There were 36
      confirmed cases of hyperparathyroidism. Based on a relative risk model, the
      excess relative risk increased significantly by 0.11/centigray; however, the
      confidence interval was wide (95% confidence interval, 0.0-17.2). The
      hyperparathyroidism rates and dose-response relationships were not affected by
      gender or age at first radiation treatment. The demonstration of a dose-response
      relationship within an irradiated cohort supports an association between
      radiation exposure and hyperparathyroidism and suggests that the calcium levels
      of individuals irradiated to the head and neck area should be monitored.

PMID- 7829623
TI  - A randomized trial for the treatment of mild iodine deficiency during pregnancy:
      maternal and neonatal effects.
AB  - One hundred and eighty euthyroid pregnant women were selected at the end of the
      first trimester of gestation on the basis of biochemical criteria of excessive
      thyroid stimulation, defined as supranormal serum thyroglobulin (TG > 20
      micrograms/L) associated with a low normal free T4 index (< 1.23) and/or an
      increased T3/T4 ratio (> 25 x 10(-3)). Women were randomized in a double blind
      protocol into three groups and treated until term with a placebo, 100 micrograms
      potassium iodide (KI)/day, or 100 micrograms iodide plus 100 micrograms L-T4/day.
      Parameters of thyroid function, urinary iodine excretion, and thyroid volume were
      monitored sequentially. Neonatal thyroid parameters, including thyroid volume by
      echography, were also assessed in the newborns from mothers of the three groups.
      In women receiving a placebo, the indices of excessive thyroid stimulation
      worsened as gestation progressed, with low free T4 levels, markedly increased
      serum TG and T3/T4 ratio. Serum TSH doubled, on the average, and was supranormal
      in 20% of the cases at term. Urinary iodine excretion levels were low, around 30
      micrograms/L at term. The thyroid volume increased, on the average, by 30%, and
      16% of the women developed a goiter, confirming the goitrogenic stimulus
      associated with pregnancy. Moreover, the newborns of these mothers had
      significantly larger thyroid volumes at birth as well as elevated serum TG
      levels. In both groups of women receiving an active treatment, the alterations in
      thyroid function associated with pregnancy were markedly improved. The increase
      in serum TSH was almost suppressed, serum TG decreased significantly, and changes
      in thyroid volume were minimized (group receiving KI) or almost suppressed (group
      receiving KI combined with L-T4). Moreover, in the newborns of the mothers in the
      two groups receiving an active treatment, serum TG was significantly lower, and
      thyroid volume at birth was normal. The effects of therapy were clearly more
      rapid and more marked in the group receiving a combination of T4 and KI than in
      the women receiving KI alone. The differences could be partly attributed to the
      slightly higher amount of iodine received by women in the combined treatment.
      However, the main benefits of the combined treatment were almost certainly
      attributable to the hormonal effects of the addition of L-T4. Furthermore, the
      study demonstrated that the administration of T4 did not hamper the beneficial
      effect of iodine supplementation. In conclusion, the present work emphasizes the
      potential risk of goitrogenic stimulation in both mother and newborn in the
      presence of mild iodine deficiency.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7829624
TI  - Sulfonylurea therapy improves glucose disposal without changing skeletal muscle
      GLUT4 levels in noninsulin-dependent diabetes mellitus subjects: a longitudinal
      study.
AB  - A major pathological feature of noninsulin-dependent diabetes (NIDDM) is
      defective insulin-stimulated glucose transport in skeletal muscle. When NIDDM
      subjects are assessed as a group, GLUT4 gene expression in skeletal muscle varies
      widely and is not different from that in controls. Thus, longitudinal studies are
      needed to assess whether changes in GLUT4 expression in muscle of NIDDM subjects
      could be responsible for changes in glucose disposal. The question is timely
      because recent studies in transgenic mice show that increasing GLUT4 expression
      can increase insulin-stimulated glucose uptake in vivo and in vitro. Here we use
      a longitudinal design to investigate the effects of 8 weeks of therapy with the
      sulfonylurea gliclazide on glycemic control, glucose tolerance, insulin
      stimulated glucose disposal, and GLUT4 expression in muscle of 10 obese NIDDM
      subjects. Subjects were on a weight-maintaining diet. Gliclazide treatment
      results in increased serum C-peptide, decreased hemoglobin-A1c, decreased glucose
      excursion on glucose tolerance test, and 35% increased insulin-stimulated glucose
      disposal. Gliclazide therapy is not associated with any change in DNA or protein
      content per g muscle or any alteration in GLUT4 levels expressed either per
      microgram membrane protein or per DNA. In summary, the improvement in glycemic
      control and glucose disposal in NIDDM subjects receiving gliclazide therapy
      cannot be explained by increased expression of GLUT4 in muscle. Thus, therapeutic
      effects on insulin-stimulated glucose disposal can be achieved in NIDDM subjects
      without altering GLUT4 expression in muscle.

PMID- 7829625
TI  - A potential novel mechanism for precocious puberty in juvenile hypothyroidism.
AB  - Some children with juvenile hypothyroidism exhibit unexplained precocious
      puberty. Interaction of TSH with the human FSH receptor (hFSH-R) is a possible
      pathophysiological mechanism for this syndrome that has not been explored due to
      the lack of hFSH-free TSH preparations and the scarcity of a suitable hFSH-R
      based assay system. To devise an in vitro FSH bioassay suitable for exploring
      this mechanism, we expressed hFSH-R complementary DNA in COS-7 cells and
      stimulated them with recombinant hTSH (rec-hTSH). Rec-hTSH elicited a dose
      dependent cAMP response in the in vitro hFSH-R bioassay; however, the
      concentration of rec-hTSH required for half-maximal stimulation was several logs
      greater than that of hFSH. Rec-hTSH acted as a competitive inhibitor of hFSH at
      the hFSH-R, indicating that hTSH and hFSH are acting through the same receptor,
      namely the hFSH-R. This provides a potential novel mechanism for the precocious
      puberty of juvenile hypothyroidism.

PMID- 7829626
TI  - Increased disorderliness and amplified basal and pulsatile aldosterone secretion
      in patients with primary aldosteronism.
AB  - To investigate the pathophysiology of altered aldosterone secretion in patients
      with primary aldosteronism, the pulsatile mode of in vivo aldosterone and
      cortisol release was examined by quantitative deconvolution analysis in 5 normal
      subjects (controls) and 10 patients with aldosterone-producing adenomas (APA)
      under conditions of sodium (150 meq/day) balance. Episodic release of aldosterone
      and cortisol was assessed by sampling blood at 10-min intervals for 24 h. A
      waveform-independent deconvolution algorithm was used to calculate endogenous
      aldosterone and cortisol secretion rates on a sample by sample basis in each
      subject. There were no differences in the number of aldosterone or cortisol
      secretory bursts per day or their mean interpulse intervals between normal
      subjects and patients with primary aldosteronism. A 24-h rhythmicity in serum
      aldosterone concentrations was maintained in APA patients. Patients with primary
      aldosteronism had significantly higher (P < 0.01) aldosterone mean secretory
      rates, mean mass of aldosterone secreted per burst, maximal aldosterone secretion
      rates attained within each burst, and mean basal (nadir) aldosterone secretion
      rates. A recently introduced regularity statistic, approximate entropy (ApEn),
      was used to test for orderliness (small ApEn) vs. randomness (large ApEn) in the
      aldosterone time series. ApEn was significantly larger for the APA patients
      (1.433 +/- 0.148) than for normal subjects (0.306 +/- 0.098; P < 0.001), with
      complete group segmentation yielding 100% sensitivity and specificity. In
      contrast, a scale-invariant form of this measure, normalized ApEn, showed no
      significant distinction between tumoral and normal aldosterone release patterns.
      These ApEn findings taken together are consistent with the deconvolution results
      from an entirely distinct perspective, reinforcing an amplitude difference, but
      no frequency difference, between normal subjects and APA patients. Unexpectedly,
      patients with APA had significantly lower mean cortisol secretory rates, reduced
      cortisol secretory burst mass, and attenuated maximal cortisol secretory rates
      than normal subjects (P < 0.01). Plasma cortisol and aldosterone concentrations
      in patients remained positively correlated over short time lags. In summary, the
      present findings demonstrate that in normal subjects and patients with APA, both
      aldosterone and cortisol are secreted in a burst-like mode. The presence of
      substantial basal aldosterone release and increased irregularity of serial
      aldosterone concentrations distinguishes APA from normal subjects.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7829627
TI  - Variations of steroid hormone metabolites in serum and urine in polycystic ovary
      syndrome after nafarelin stimulation: evidence for an altered corticoid
      excretion.
AB  - To evaluate the clinical relevance of testing pituitary-ovarian responses in
      patients suffering from polycystic ovary syndrome (PCOS) with the GnRH agonist
      nafarelin, a 1.2-mg dose of nafarelin was given intranasally to 19 women with
      PCOS and 15 healthy premenopausal women. The subsequent analysis of steroids in
      both serum and urine during the test was carried out at several time points for
      up to 24 h. Serum levels of 17 alpha-hydroxyprogesterone were elevated at all
      time points of the test in PCOS patients vs. controls [at baseline, 3.5 +/- 0.2
      vs. 1.8 +/- 0.1 nmol/L (P < 0.001); at 24 h, 9.9 +/- 0.9 vs. 4.9 +/- 0.3 nmol/L
      (P < 0.001)]. Basal levels of androstenedione were higher in the patient group,
      but there was no significant change during the test in either group. Serum
      testosterone levels were also found to differ in PCOS patients compared with the
      control values at baseline (2.2 +/- 0.2 vs. 1.5 +/- 0.1 nmol/L; P < 0.05) and
      after nafarelin treatment (at 24 h, 3.2 +/- 0.4 vs. 1.8 +/- 0.2 nmol/L; P <
      0.05). Serum estradiol levels rose significantly in both groups during the test;
      the posttest levels were significantly higher in PCOS than in controls. The PCOS
      patients displayed a significant increase in androgen and gestagen metabolites as
      well as in glucocorticoid metabolites excreted in the urine during the 24 h. In
      the control subjects, except for 17 alpha-hydroxypregnanolone, which rose
      significantly, none of the urinary steroids investigated showed relevant changes
      during the nafarelin test. The posttest excretion of allo-tetrahydrocortisol (1.4
      +/- 0.2 vs. 0.3 +/- 0.1 mumol/g creatinine; P < 0.001) and the increase in 17
      alpha-hydroxypregnanolone excretion (1.4 +/- 0.2 vs. 0.3 +/- 0.1 mumol/g
      creatinine; P < 0.001) were distinctly higher in PCOS patients than in the
      controls; the diagnostic sensitivity of the combination of both parameters was
      89% at a 93% specificity. Thus, measurements of 17 alpha-hydroxyprogesterone
      levels in serum and of urinary allo-tetrahydrocortisol and 17 alpha
      hydroxypregnanolone after nafarelin treatment make this stimulation test a
      valuable diagnostic tool for identifying PCOS patients. The significant changes
      in the excretion of urinary androgen and gestagen metabolites, unmasked by GnRH
      agonist stimulation, suggest a functional alteration of the pituitary-ovarian
      axis. The reason for the increased excretion of glucocorticoid metabolites after
      nafarelin stimulation remains to be clarified.

PMID- 7829628
TI  - Familial medullary thyroid cancer and prominent corneal nerves: clinical and
      genetic analysis.
AB  - A unique kindred manifesting medullary thyroid carcinoma and corneal nerve
      thickening without other aspects of the multiple endocrine neoplasia syndrome
      (MEN) was analyzed by linkage analysis using four highly polymorphic (CA)n repeat
      markers (sTCL-1, D10S141, ZNF22, and sJRH-1). Additionally, the RET protooncogene
      was examined for specific mutations by DNA sequence analyses in all affected
      family members. Screening of 11 family members spanning 4 generations revealed 7
      subjects with corneal nerve thickening; of these subjects, 3 had abnormal
      pentagastrin-stimulated calcitonin studies, and these 3 subjects were each found
      to have C-cell hyperplasia or medullary thyroid carcinoma at surgery. Linkage
      analysis showed cosegregation of alleles (as defined by the above markers), with
      the presence of both corneal nerve thickening and medullary thyroid carcinoma/C
      cell hyperplasia (maximum LOD score, 2.69; consistent with, but not proving
      linkage). DNA sequence analysis showed that none of the affected individuals had
      mutations in either exon 10 or 11, or in exon 16 of the RET protooncogene,
      regions where mutations have been described for MEN type 2A (MEN-2A) and MEN-2B
      families, respectively. Thus, compared to the defined syndromes of MEN-2A and MEN
      2B, this kindred appears to represent a true clinical overlap syndrome whose
      genetic basis may be distinct from these two syndromes.

PMID- 7829629
TI  - Proprotein convertases (PC1/PC3 and PC2) in normal and neoplastic human tissues:
      their use as markers of neuroendocrine differentiation.
AB  - By immunocytochemistry and immunoblotting, we examined normal and neoplastic
      human tissues with polyclonal antibodies raised against selected peptide regions
      of proprotein convertase-2 and -3 (PC2 and PC3), two proteases that have been
      shown to selectively cleave neuroendocrine precursor molecules at pairs of basic
      residues. Immunoreactivity for both enzymes was detected in neuroendocrine cells
      of pituitary, gut, pancreas, thyroid, and adrenals and in tumors thereof, but was
      absent in thyroid follicular cells, parathyroids, adrenal cortex, testes, and a
      number of nonneuroendocrine tissues, both normal and tumorous. Although both PCs
      were virtually universal concomitants of the neuroendocrine system, cells with a
      neural phenotype (e.g. pheochromocytes and Merkel cells) predominantly contained
      PC2, whereas classic endocrine cells contained mostly PC3. PC3 immunoreactive
      cells were abundant all along the gastrointestinal tract, whereas PC2 was highly
      expressed only in the pyloric antrum and proximal third of duodenum. Double
      immunostaining experiments revealed colocalization of PC3 with virtually all
      gastrointestinal peptides, whereas PC2 immunoreactivity was mostly expressed in
      gastrin, cholecystokinin, and somatostatin cells. Noticeably, the proportion of
      glucagon-producing cells immunoreactive for PC3 was high in the gut and low in
      pancreatic islets and glucagonomas, whereas the reverse occurred for PC2. At the
      ultrastructural level, immunostaining was confined to the mature dense core
      granules, the site of storage of granins and peptide hormones. With the exception
      of parathyroid cells, PC2 and/or PC3 expression correlated with the occurrence of
      granins, canonical markers of the secretory granules. Immunoblotting experiments
      confirmed the identity of the immunocytochemical reactivities. It is concluded
      that PC2 and PC3 are highly sensitive markers of neuroendocrine differentiation
      and have distinct distribution patterns, and that antibodies to these enzymes may
      play an important role in the analysis of tumors.

PMID- 7829630
TI  - Clinical review 65. Evaluation and treatment of the patient with a pituitary
      incidentaloma.
AB  - Incidental pituitary adenomas are being found commonly with our improved
      neuroradiological imaging procedures. Screening for hormone oversecretion by
      these tumors appears to be warranted. For patients with macroadenomas, patients
      should also be screened for hypopituitarism. In the absence of visual field
      abnormalities or hypothalamic/stalk compression, it may be appropriate to observe
      such patients carefully with repeated CT or MRI scans. A limited amount of data
      suggests that significant tumor enlargement will occur in less than 15% of
      patients with microadenomas (7). However, all macroadenomas must start out as
      microadenomas, so periodic follow-up is indicated to assess this possibility.
      Macroadenomas, by their very existence at the time of detection, have already
      indicated a propensity for growth. Over the limited period of follow-up in the
      two series reported, significant growth occurred in almost one third of patients
      with macroadenomas (7, 8). Hemorrhage into such tumors is uncommon, but
      anticoagulation may predispose to this complication. When there is no evidence of
      visual field deficits, an attempt at medical therapy with a dopamine agonist is
      reasonable, realizing that only about 10% of such patients will respond with a
      decrease in tumor size. Surgery is indicated if there is evidence of tumor
      enlargement, especially when such growth is accompanied by compression of the
      optic chiasm, cavernous sinus invasion, or the development of pituitary hormone
      deficiencies.

PMID- 7829631
TI  - Primary hyperparathyroidism: is technetium 99m-Sestamibi/iodine-123 subtraction
      scanning the best procedure to locate enlarged glands before surgery?
AB  - Technetium99m (99mTc)-Sestamibi/123I subtraction scanning was prospectively
      performed in 30 patients with primary hyperparathyroidism in an attempt to locate
      enlarged glands before first surgery. Imaging results were compared to surgical
      findings; the surgeon tried to identify all parathyroid glands. Twenty-seven
      patients were found to have a solitary adenoma during surgery, and 3 had
      multiglandular parathyroid hyperplasia. Twenty-six parathyroid adenomas (96%)
      were accurately located before surgery. The smallest gland detected weighted 125
      mg. Preoperative detection of two mediastinal adenomas allowed them to be excised
      by median sternotomy during the initial operation. 99mTc-Sestamibi/123I
      subtraction scanning predicted multiglandular involvement in two patients with
      parathyroid hyperplasia, whereas it showed a solitary image in the third. Ten
      patients (33%) had associated nodular thyroid disease, hindering image analysis
      and leading to one false positive result. 99mTc-Sestamibi scanning seems to be
      better for locating enlarged parathyroid glands than other noninvasive imaging
      techniques. However, 1) difficulties associated with thyroid nodules call for
      complementary thyroid scanning; and 2) images showing a solitary enlarged
      parathyroid gland do not rule out multiglandular disease. This technique should
      help in detecting lesions, such as mediastinal glands, that are difficult to find
      at initial surgery.

PMID- 7829632
TI  - Tamoxifen inhibits growth, migration, and invasion of human follicular and
      papillary thyroid cancer cells in vitro and in vivo.
AB  - Prognosis of differentiated thyroid cancer is best in young women. It has been
      proposed that sex steroids protect premenopausal women from aggressive thyroid
      malignancies. Some thyroid tissues have estrogen receptors, and estrogen
      stimulates human thyroid cells. Tamoxifen is thought to exert its
      antiproliferative effects mainly by blocking estrogen stimulation. However,
      recently, mechanisms independent of estrogen interactions were found to be
      important for the favorable effect. We investigated the effect of tamoxifen on
      the growth, migration, and invasion in three follicular thyroid cancer cell lines
      (FTC133, primary; FTC236, lymph node; and FTC238, lung metastasis) from one
      patient and two papillary lines (PTC-UC1 and PTC-UC3). Growth was measured by
      dimethylthiazol-diphenyltetrazolium bromide assays, and migration was determined
      by the ability of cells to penetrate 8-microns pore membranes, which were covered
      by Matrigel for invasion assays. For in vivo experiments, we used xenografts of
      FTC133 in nude mice. Tamoxifen (1.5 mumol/L) inhibited the growth of all thyroid
      cancer cell lines (FTC133, 59%; FTC236, 42%; FTC238, 46%; P < 0.01). This effect
      was less pronounced in PTC-UC1 (25%) and PTC-UC3 (19%; P < 0.006) cell lines.
      Tamoxifen also inhibited migration and invasion of FTC more than PTC. Invasion of
      FTC133 was inhibited by 36% (P < 0.01), FTC236 by 30%, and FTC238 by 32%.
      Immunohistochemistry showed no estrogen receptors in any cell line. Also,
      estradiol had no significant effect on the growth, migration, or invasion of FTC
      or PTC. Tamoxifen treatment inhibited the growth of FTC133 xenografts in nude
      mice by 52% compared to that in placebo-treated controls (P < 0.002). In
      conclusion, tamoxifen inhibited the growth, migration, and invasion of
      differentiated thyroid cancer cells in vitro and in vivo. This was not reversed
      by estrogen. Tamoxifen acts independently of estrogen interactions and may be
      useful as an adjuvant treatment for some differentiated human thyroid
      malignancies.

PMID- 7829633
TI  - Lipoatrophic diabetes: genetic exclusion of the insulin receptor gene.
AB  - Lipoatrophic diabetes (LD) is a syndrome with congenital or delayed onset,
      characterized by severe insulin resistance and generalized lipoatrophy. Using
      denaturing gradient gel electrophoresis and sequencing, we have investigated the
      contribution of defects in the insulin receptor (IR) gene in LD. First, we
      performed an association study between the IR gene and congenital lipoatrophy in
      two families with consanguineous parents and one or two affected children
      (patients D1, D2, and D3). Segregation analysis of intragenic polymorphisms
      excluded a linkage between the IR locus and the LD phenotype in both families.
      Second, we screened for mutations in all exons and splice site junctions of the
      IR gene from patients D1-D3 and 11 additional unrelated patients with congenital
      or delayed forms of LD. The IR sequence proved to be normal in all 14 subjects
      because nucleotide variations that we detected were silent. The relative levels
      of expression of the 2 alleles of the IR gene were evaluated by allele-specific
      oligonucleotide hybridization in cells from most of these patients, and no gross
      alteration was detected. Overall, these results provide the first clear evidence
      against the involvement of the IR gene in the pathogenesis of any clinical form
      of LD.

PMID- 7829634
TI  - Thyroid function in non-growth hormone-deficient short children during a placebo
      controlled double blind trial of recombinant growth hormone therapy.
AB  - GH treatment in GH-deficient children has been reported to cause decreases in
      serum T4 and TSH and an increase in serum T3. We sought to determine whether GH
      treatment alters thyroid function in non-GH-deficient short children. Twenty
      children (18 boys) were followed for 12 months while receiving either GH
      (Humatrope, Eli Lilly; 0.074 mg/kg, sc, 3 times/week; n = 9) or placebo (n = 11).
      Total T4, free T4, T3, and TSH were measured every 6 months and in 12 children
      also at 1, 2, 3, and 9 months. A TRH test and measurement of nocturnal TSH surge
      were performed at baseline and after 6 months of treatment in 19 subjects. There
      were no significant differences at baseline in the clinical features between the
      placebo and GH groups. Total T4, free T4, T3, and TSH levels did not
      significantly differ between the placebo and GH groups at baseline and at 1, 2,
      3, 6, 9, and 12 months. There were no significant differences between the two
      groups in TSH response to TRH or nocturnal TSH surge. Although an early transient
      effect of GH treatment could not be excluded, we conclude that GH treatment for
      12 months does not produce sustained alterations in thyroid function in non-GH
      deficient children.

PMID- 7829635
TI  - Genetic selection in nonclassical adrenal hyperplasia.

PMID- 7829636
TI  - The continuous low dose insulin and glucose infusion test: a simplified and
      accurate method for the evaluation of insulin sensitivity and insulin secretion
      in population studies.
AB  - In this study we investigated a simple nonlabor-intensive method to evaluate
      insulin sensitivity and beta-cell function which is suitable for application in
      population studies. The method is a refinement of the modified Harano test and
      consists of a continuous low dose insulin (25 mU/kg.h) and glucose (4 mg/kg.min)
      infusion test (LDIGIT) lasting 150 min. Insulin sensitivity was evaluated as the
      MCR of glucose divided by the steady state serum insulin level achieved at the
      end of the test. Insulin secretion was expressed as the incremental area for C
      peptide concentration during the first 15 min of the test. We compared the
      indices of insulin sensitivity and insulin secretion yielded by LDIGIT with those
      derived from the euglycemic clamp and the hyperglycemic clamp, respectively.
      Fifty-four subjects underwent a LDIGIT (33 with normal glucose tolerance and 21
      with impaired glucose tolerance); of the 54, 19 were submitted to a euglycemic
      clamp, 18 to a hyperglycemic clamp, and 10 to a modified Harano test (insulin
      infusion, 50 mU/kg.h; glucose infusion, 6 mg/kg.min). LDIGIT overcame the
      drawbacks associated with the modified Harano test because it resulted in more
      stable final glucose levels and prevented the occurrence of hypoglycemic
      episodes. No significant differences were found between the insulin sensitivity
      index (ISI) of the LDIGIT and that of the euglycemic clamp for each group of
      subjects. Moreover, there was a strong correlation between the ISI determined by
      LDIGIT and the ISI determined by clamp (r = 0.90; P < 0.0001), and the best
      regression line was not different from the identity line, suggesting that the two
      indices are equivalent. The index of insulin secretion provided by LDIGIT
      correlated well with that of the hyperglycemic clamp (r = 0.82; P < 0.001) and
      was significantly higher in overweight subjects than in normal weight subjects.
      In conclusion, LDIGIT is a simple and accurate method to assess insulin
      sensitivity and secretion. It can be useful in population studies and in
      situations when more complex techniques are not feasible.

PMID- 7829637
TI  - CTLA-4 gene polymorphism associated with Graves' disease in a Caucasian
      population.
AB  - Graves' disease (GD) is an autoimmune thyroid disease. Multiple genetic factors
      are believed to be involved in its pathogenesis, but the factors are largely
      unknown, except for sex (female disease preponderance) and the role of human
      leukocyte antigen (HLA) genes on chromosome 6. To understand the mechanisms
      underlying the development of GD, a search for non-HLA-linked genes is crucial,
      and we tested several candidate genes, including the CTLA-4 gene on chromosome
      2q33. CTLA-4 molecules may either facilitate or down-regulate the second signal
      to T-cells, which is provided by the interaction between the two accessory
      molecules CD28 and B7. One hundred and thirty-three Caucasian patients (26 males)
      with GD and 85 local controls were included in this study. Polymerase chain
      reaction was used to amplify DNA containing the (AT)n repeat within the 3'
      untranslated region of exon 3 of the CTLA-4 gene. The 5'-forward primer was
      radiolabeled, and amplified products were resolved on 5-7% sequencing gels. All
      subjects were previously typed for HLA class II alleles. Twenty-one alleles were
      observed with sizes ranging from 88-134 basepairs. In the association analysis,
      the genotype frequencies between GD patients and controls differed significantly
      (P = 0.012), and the difference was attributable to a higher frequency of the 106
      basepair allele among patients (relative risk, 2.82). When the patients were
      subdivided with respect to sex and HLA, the phenotype frequencies of allele 106
      was higher in the female patients with protective HLA specificities (DQA1*0201
      positive/DQA1*0501 negative) than in those with susceptible HLA specificities
      (DQA1*0201 negative/DQA1*0501 positive; 81.8% vs. 45.5%; P = 0.026). The CTLA-4
      gene or a closely associated gene (including CD28) confers susceptibility to GD.
      This association may be more important in female patients with protective HLA
      specificities, who otherwise would be at low risk of developing the disease.

PMID- 7829638
TI  - Human autoantibodies to the thyrotropin receptor: recognition of linear, folded,
      and glycosylated recombinant extracellular domain.
AB  - To examine the heterogeneity of autoantibodies to the human TSH receptor (hTSHR),
      we evaluated 20 sera from patients with Graves' disease for their recognition of
      prokaryotic (unglycosylated) and eukaryotic (insect cell glycosylated)
      recombinant hTSHR extracellular domain (ecd) in an unfolded (linear) and a folded
      (nonlinear) state. With the prokaryotic antigen, 12 (60%) bound folded hTSHR ecd
      monomer, 8 (40%) bound to the unfolded monomer, and 3 (15%) bound to a tetrameric
      species. Such binding to different hTSHR antigens was not mutually exclusive. In
      addition, 7 (35%) sera showed an apparently higher reactivity for the folded than
      the unfolded monomer. When reacted against the glycosylated insect cell hTSHR
      ecd, 9 (45%) sera recognized both the unfolded and folded monomer, and 5 (25%)
      recognized the tetrameric form. In all of our testing, 17 of the 20 sera (85%)
      bound to 1 or more of the recombinant hTSHR ecd antigens, and the recognition
      pattern appeared to be heterogeneous in at least 4 (20%) of the serum samples,
      with hTSHR antibodies recognizing linear, folded, and glycosylated hTSHR ecd
      monomers. We conclude, therefore, that patients with Graves' disease have
      autoantibodies that recognize multiple epitopes on the hTSHR ecd and that it is
      possible to classify them according to their recognition of linear, folded, and
      glycosylated products.

PMID- 7829639
TI  - The concordance of pulsatile ultradian release of adrenocorticotropin and
      cortisol in male rhesus monkeys.
AB  - The ultradian release of ACTH and cortisol was investigated in six male rhesus
      monkeys (Macaca mulatta) with an intensive (2-min) blood-sampling procedure to
      investigate micropulsatile hormone secretory patterns. A sensitive and specific
      immunoradiometric assay was used to measure plasma ACTH concentrations. An
      objective pulse detection algorithm (Cluster) was used to assess the pulsatility
      of ACTH and cortisol release. The temporally coincident release of ACTH and
      cortisol was also examined. Venous blood samples were collected (over < 15 s)
      every 2 min for 120 min beginning at 1300 h. The number of ACTH peaks (3.2
      peaks/h), interpulse intervals (19 +/- 2.4 min), and pulse amplitudes (9.7 +/-
      1.6 pmol/L) in rhesus monkey were similar to corresponding measures of ACTH
      release in humans (3.3 peaks/h, 18 +/- 0.8 min, and 4.7 +/- 1.0 pmol/L,
      respectively). The number of cortisol peaks (2.3 peaks/h), interpulse interval
      (26 +/- 8.6 min), and other characteristics of pulsatile cortisol release were
      also determined. There was a 32.4% exact concordance of ACTH with cortisol peaks
      (11 of 34; P < 0.001). Fifty-six percent of ACTH peaks (19 of 34) were followed
      by a cortisol peak within 10 min (P < 0.02). There was a significant correlation
      between the ACTH and coincident cortisol pulse amplitudes (P < 0.0001). The
      amplitudes of ACTH peaks coincident with cortisol peaks at 0 min time lag were
      significantly higher than ACTH peaks not temporally coupled with cortisol peaks.
      Our data indicate that 1) high frequency, low amplitude micropulsatile ACTH
      secretion in rhesus monkeys is very similar to the high frequency ACTH rhythm in
      humans; 2) temporally concordant ACTH and cortisol release episodes may be
      amplitude coupled; and 3) an adequate incremental ACTH pulse amplitude may elicit
      a concurrent cortisol release episode from the adrenal cortex. These data suggest
      that the rhesus monkey is a potentially useful model for the study of
      neuroendocrine control of ACTH release.

PMID- 7829640
TI  - Comparison of the pharmacokinetics of parenteral parathyroid hormone-(1-34) [PTH
      (1-34)] and PTH-related peptide-(1-34) in healthy young humans.
AB  - The amino-terminal fragments of human PTH [hPTH-(1-34)] and PTH-related peptide
      [PTHrP-(1-34)] appear to be equipotent in several rodent models. However,
      continuous i.v. infusions of these peptides to young human volunteers suggested
      that a 10-fold higher molar dose of PTHrP was required to produce comparable
      circulating levels of the peptide and biochemical responses similar to PTH. As
      PTHrP has a wide variety of target tissues in mammalian species and may,
      therefore, play a paracrine, rather than an endocrine, hormonal role in vivo, we
      evaluated whether enhanced metabolic clearance of injected PTHrP might explain
      its apparently reduced potency as a PTH-like hormone. Ten healthy subjects [age,
      25 +/- 9 (+/- SD) yr] received in random order either hPTH-(1-34) or hPTHrP-(1
      34) given by bolus i.v. injections in a dose of 10.7 nmol. Measurements of plasma
      immunoreactive peptide indicated a comparable volume of distribution for each,
      but the apparent t1/2 (8.3 +/- 1.6 min) and plasma clearance (4.0 +/- 1.4 L/min)
      for hPTHrP were significantly (P < 0.05) accelerated compared to those of hPTH
      (t1/2, 10.2 +/- 0.5 min; clearance, 2.0 +/- 0.4 L/min). Peak plasma cAMP levels
      were 9-fold lower in response to hPTHrP (29.5 +/- 19 vs. 190 +/- 63 pmol/L; P <
      0.01), and increases in urinary cAMP excretion were 5-fold lower (2.1 +/- 1.1 vs.
      11.2 +/- 3.7 nmol/mmol creatinine; P < 0.01). No major differences were observed
      in the urinary excretion of phosphate, calcium, or sodium between the two
      peptides. Although hPTHrP-(1-34) has a 2-fold higher MCR than hPTH-(1-34), this
      may not explain the more than 5-fold lower plasma or urinary cAMP response to
      PTHrP in humans. The comparable effects of PTH and PTHrP on urinary phosphate,
      calcium, and sodium may indicate a non-cAMP-dependent pathway for these
      responses, although the intracellular pool of cAMP generated to either peptide,
      and thus the local target tissue response, could not be estimated in the present
      study.

PMID- 7829641
TI  - Adrenocorticotropin receptor gene mutations in familial glucocorticoid
      deficiency: relationships with clinical features in four families.
AB  - Familial glucocorticoid deficiency is an autosomal recessive syndrome of adrenal
      unresponsiveness to ACTH characterized by glucocorticoid deficiency, high plasma
      ACTH levels, and a normal renin-aldosterone axis. Defects of the ACTH receptor
      have been suggested as a possible cause, and we have previously reported a number
      of novel mutations of the ACTH receptor gene in some, but not all, cases,
      suggesting that familial glucocorticoid deficiency may have a heterogeneous
      molecular etiology. Here we report the clinical features and ACTH receptor gene
      analysis in four patients from different families. We found that two patients
      were compound heterozygotes for the S74I and R128C mutations (patient A) and I44M
      and L192fs frame shift mutations (patient B). The other two patients (C and D)
      were of different ethnic ancestry, but were both homozygous for a R146H mutation.
      Segregation studies within families revealed heterozygosity in the parents and
      several other family members. Human CRH tests in the parents of patients A and B
      showed normal cortisol and ACTH responses in the S74I, R128C, and I44M
      heterozygotes and exaggerated cortisol and ACTH responses in the L192fs
      heterozygote, suggesting that the physiological ACTH increment induced in this
      test did not reveal evidence of subclinical ACTH resistance, and that this test
      may not be of value in ascertaining heterozygosity.

PMID- 7829642
TI  - Primary hyperparathyroidism: preoperative localization using technetium-sestamibi
      scanning.

PMID- 7829643
TI  - Adults with growth hormone deficiency have abnormal body composition but normal
      energy metabolism.
AB  - We compared body composition and energy metabolism in a cross-sectional study
      involving 21 GH-deficient (GHD) and 29 normal adults. Fifteen subjects from each
      group were pair-matched for age, sex, height, and weight. Comparison of body
      composition by dual energy x-ray absorptiometry in the 15 pairs showed that GHD
      subjects had a significantly greater fat mass (23.9 +/- 1.8 vs. 19.8 +/- 2.6 kg;
      P = 0.02), lower bone mineral content (2.6 +/- 0.1 vs. 2.9 +/- 0.1 kg; P = 0.06),
      and lower fat-free soft tissue mass (FFSTM; 45.8 +/- 2.5 vs. 48.9 +/- 2.6 kg; P =
      0.02). To determine which subcompartment changes were responsible for the reduced
      FFSTM in GH deficiency, extracellular water (ECW) was measured by 24Na dilution
      in 11 of the subject pairs, and body cell mass (BCM) was derived by subtracting
      ECW from FFSTM. The GHD subjects had lower ECW (19.4 +/- 1.0 vs. 21.0 +/- 1.0 kg;
      P = 0.05) and BCM (26.6 +/- 1.9 vs. 28.6 +/- 2.1 kg; P = 0.08) than their normal
      counterparts, with the difference approaching statistical significance. When the
      relationship between ECW and FFSTM was compared in the larger group of 18 GHD and
      27 normal subjects, no statistically significant difference was found between the
      2 regression lines, indicating that ECW and BCM were proportionately reduced in
      GH deficiency. Energy expenditure and fuel utilization before and after a
      standardized mixed meal were measured by indirect calorimetry in 12 matched pairs
      of GHD and normal subjects. Comparison of energy expenditure and fuel utilization
      showed no significant difference in fasting or postprandial energy expenditure,
      or carbohydrate or fat oxidation rates between the two groups. We conclude that
      GHD adults have an increased FM, a reduced FFSTM due to a proportionate reduction
      in ECW and BCM, and no detectable disturbance in energy metabolism.

PMID- 7829644
TI  - Isolated hyponatremia after transsphenoidal pituitary surgery.
AB  - A retrospective analysis was performed to study the fluid and sodium status of
      patients undergoing transsphenoidal surgery (TS) for Cushing's disease. We
      evaluated the time of onset, duration, and relative incidence of isolated
      hyponatremia and identified possible factors associated with it. Of 58 patients
      that underwent TS over 1 yr, 52 without postoperative diabetes insipidus or
      volume depletion were studied. Isolated hyponatremia after TS for Cushing's
      disease occurred in 21%, and symptomatic hyponatremia (plasma sodium, < or = 125
      mmol/L) with new onset headache, nausea, and emesis occurred in 7.0% of all
      operated. These later patients escaped monitoring and intervention for 24 h. The
      development of hyponatremia began early in the postoperative period and
      progressed slowly over 7 days. Maximum antidiuresis occurred on postoperative day
      7. Vasopressin levels measured in two patients while hypoosmolar suggested that
      unregulated vasopressin release contributed to the hyponatremia. Cortisol levels,
      glucocorticoid replacement, and pituitary adenoma size were similar in
      normonatremic and hyponatremic patients. Patients combining a history of an
      estrogenic milieu and documented posterior pituitary trauma at surgery
      experienced lower nadir plasma sodium. All hyponatremic patients were fluid
      restricted, and none developed progressive neurological symptoms, morbidity, or
      mortality. We speculate that the mild degree and slow rate of development of
      hyponatremia and/or active monitoring and intervention contributed to the good
      outcome.

PMID- 7829645
TI  - Marked hypocholesterolemia in a case with adrenal adenoma--enhanced catabolism of
      low density lipoprotein (LDL) via the LDL receptors of tumor cells.
AB  - A 16-yr-old girl was hospitalized because of amenorrhea and virilism, and was
      diagnosed with an adrenal tumor on the right side. Her serum androgen levels were
      markedly elevated, and severe hypocholesterolemia (total cholesterol, 0.59
      mmol/L) was observed. After resection of the tumor, her serum cholesterol level
      dramatically rose to normal, suggesting a role of this tumor in her marked
      hypocholesterolemia. To investigate the mechanism of hypocholesterolemia in this
      case, we examined the effects of dehydroepiandrosterone and
      dehydroepiandrosterone sulfate on the low density lipoprotein (LDL) receptor
      activity of fibroblasts. These hormones did not have any effect on LDL receptor
      activity. Northern blot analysis demonstrated that the LDL receptor messenger
      ribonucleic acid level of this tumor tissue was increased about 8-fold compared
      with that of normal adrenal cortex. The LDL receptor activity of the cultured
      cells established from this tumor was 2-fold higher than that of Hep G2 cells.
      Furthermore, the LDL receptor activity could not be down-regulated by an
      excessive dose of 25-hydroxycholesterol. These results suggest that increased LDL
      receptor activity and unrestricted uptake of LDL by the adrenal tumor may have
      caused the marked hypocholesterolemia in this patient.

PMID- 7829646
TI  - The diagnostic value of urinary pyridinium cross-links of collagen, serum total
      alkaline phosphatase, and urinary calcium excretion in neoplastic bone disease.
AB  - Bone metastases strongly affect skeletal metabolism by both their growth and
      their paracrine activities. However, so far no specific laboratory marker has
      been found to signal the spread of neoplastic disease to bone. We performed a
      cross-sectional study of 153 cancer patients and an equal number of healthy
      controls matched for sex and age, in which we determined serum levels of calcium
      and total alkaline phosphatase (TAP) as well as the fasting urinary excretion of
      calcium (uCa) and of the collagen cross-links pyridinoline (uPYD) and
      deoxypyridinoline (uDPD). The aim of the study was to analyze the diagnostic
      validity of the biochemical parameters measured with regard to neoplastic bone
      involvement. In the cancer group, 98 patients had overt bone metastases, as
      judged from radiographic and radioisotopic bone imaging. The remaining 55
      patients were also in an advanced stage of disease, but there was no evidence of
      malignant bone involvement. In comparison to healthy controls, patients both with
      and without metastatic bone disease had significantly higher levels of TAP, uPYD,
      and uDPD (P < 0.0001). Only in cancer patients with bone metastases was the
      median serum calcium level higher than in the healthy controls (P < 0.02). uCa
      was the same in cancer patients and the control group. Within the collective of
      cancer patients, individuals with skeletal metastases had higher levels of serum
      calcium (P < 0.05), TAP (P < 0.01), and uPYD and uDPD (both P < 0.0001), than
      patients without evidence of malignant bone disease. uCa did not differ between
      the 2 groups of cancer patients. The cancer patients were then stratified into 4
      subgroups according to the serum calcium level (< or = 2.6 mmol/L >) and the
      absence or evidence of bone metastases. This stratification revealed that in
      patients with bone metastases, uPYD and uDPD levels were similar in normocalcemic
      and hypercalcemic subjects, whereas in hypercalcemic patients, uCa levels
      significantly exceeded those in normocalcemic patients. When the efficacy of TAP,
      uCa, uPYD, and uDPD in discriminating between patients with and without bone
      metastases was evaluated by use of receiver-operating characteristic curves and
      stepwise multivariate regression analysis, uPYD was found to have the highest
      diagnostic validity. Using 50 mumol PYD/mol creatinine (i.e. the upper limit of
      normal range) as the cut-off level, the sensitivity of uPYD was 88.7%, whereas
      the specificity was only 41.8% (odds ratio, 5.598; 95% confidence interval, 2.547
      12.306).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7829647
TI  - [Sociological aspect of terminal care at home].

PMID- 7829648
TI  - [Anatomical analysis of the basilar artery and its branches with special
      reference to the arterial anastomosis, and its course and distribution on the
      pontine ventral surface].
AB  - The morphology of the basilar artery and its branches was studied in 52 human
      brains with special reference to arterial anastomosis, and its course and
      distribution on the pontine ventral surface. The results were as follows: 1. Main
      trunk of the basilar artery (1) The average maximum and minimum external diameter
      was 3.93 +/- 0.76 mm and 3.14 +/- 0.58 mm, and the average length was 35.0 +/-
      5.1 mm. (2) Fenestration was observed in one case (1.9%). (3) The shape of
      flexion was classified into three types: S-shaped (18 cases = 34.6%), inverted S
      shaped (29 cases = 55.8%) and straight (5 cases = 9.6%). (4) The average angle of
      flexion was 32.5 +/- 24.5 degrees. A positive correlation was observed between
      age and the angle of flexion; the coefficient was 0.31. 2. Branches of the
      basilar artery (1) The average number of branches from the main trunk of the
      basilar artery was 22.8 +/- 3.94. The main trunk was divided into three equal
      portions: the rostral, intermediate and caudal. Of all the branches, 43.9% arose
      from the rostral portion, 33.3% from the intermediate portion and the remaining
      22.8% from the caudal portion. (2) Forty-eight percent of all the branches had an
      external diameter ranging from 0.35 mm to 0.55 mm, and this size was predominant
      in the branches from each of the three portions. (3) Of all the branches, 45.4%
      had a diverging angle between 45 degrees and 90 degrees. This was the predominant
      range of diverging angle in the intermediate and rostral portions. In the caudal
      portion, however, the predominant diverging angle tended to range from 0 degrees
      to 45 degrees. 3. Arterial anastomosis, course and distribution on the pontine
      ventral surface (1) Ninety-nine anastomoses were found on the pontine ventral
      surface in 42 cases. Fifty-seven anastomoses (57.5%) were found between pontine
      branches and 21 (21.3%) between a pontine branch and an anterior inferior
      cerebellar artery. More anastomoses were found in the median area than in the
      lateral area. (2) A number of arterial distributions were observed along the
      basilar sulcus in the middle and lower parts, around the facial and
      vestibulocochlear radices and around the trigeminal radix. Many branches had a
      downward distribution along the basilar sulcus in the middle and lower parts, an
      outward distribution around the facial and vestibulocochlear radices, and a
      downward or outward distribution around the trigeminal radix.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 7829649
TI  - [Stromal changes in cancer. Studies on changes of stroma promoted by gastric
      cancerous cells using alginate microcapsules].
AB  - Xenografting can be accomplished by using encapsulated cells in the alginate
      microcapsule. Using this technique, the experiment was made to investigate the
      stroma-promoting factors that were produced by the encapsulated differentiated
      (MKN-28) and undifferentiated (KATO-III) gastric cancerous cell lines.
      Fibronectin (FN) in the medium was quantified by single culture with the human
      fibroblast cell line (CCD-32Lu) and coculture with CCD-32Lu and the encapsulated
      MKN-28 ro KATO-III. Then following this procedure, each capsule including the
      gastric cancerous cells was subcutaneously transplanted into Wistar Rats. After
      14 days, the surrounding tissues of the microcapsules were stained, and the
      localization of type III collagen, 4 and 6 chondroitin sulfate, and FN were
      observed by immunohistochemical stainings. The concentration of FN in both single
      culture and coculture medium gradually increased, especially in the medium
      complemented with KATO-III and CCD-32Lu. The measured point after 48 hours
      demonstrated the obvious increase compared to the single culture and coculture
      medium. Upon the histological comparison, it was found that the stromal
      proliferation around the tissue transplanted the microcapsules including MKN-28
      or KATO-III were distributed more abundantly than the transplantation of
      microcapsules only. However, no difference was noted between the stroma of MNK-28
      and KATO-III. In conclusion, this study suggests that any stroma-promoting factor
      is produced by the gastric cancerous cells.

PMID- 7829650
TI  - [Flow cytometry studies on the long-term effect of adriamycin on cell cycles].
AB  - Little is known today about the long-term influence of the anti-cancer
      antibiotic. Adriamycin (ADR), on the cell cycle. With this in mind, the author
      used flow cytometry (FCM) to observe the changes with time in the cell cycle. The
      changes were examined every 24 hours for 14 days. Prior to this HeLa S3 cancer
      cells were cultured in three ADR concentrations--0.01 micrograms/ml, 0.1
      micrograms/ml, 1.0 micrograms/ml--. In the cell group exposed to the low ADR
      concentration of 0.01 microgram/ml for one hour, no noteworthy effect on the cell
      cycle was noted, and the cell count was slightly depressed as compared with the
      control group. In the group exposed to the moderate ADR concentration of 0.1
      micrograms/ml for one hour, the G2 phase cells increased in number after 24
      hours, but decreased on and after ten days, though there was an increase in the
      number of G1 phase cells. In addition, the cell count, which had shown no growth
      till the eight day, began to increase on and after the ninth day. In the cell
      group exposed to the high ADR concentration of 1.0 micrograms/ml for one hour,
      complete G2 block was observed on and after the 24th hour, with no subsequent
      change. The cell count also continued to decrease. The previous assumption that
      once G2 block has been caused by ADR, the cell group dies, was again shown to be
      valid.2+ e

PMID- 7829651
TI  - [Studies on the relationship between gastric acidity and the development of MRSA.
      Especially for the prevention of MRSA enterocolitis].
AB  - Enterocolitis caused by methicillin-resistant Staphylococcus aureus (MRSA) has
      recently been recognized as one of the severe postoperative complications in
      surgery on the digestive organs. This disease often occurs in the early days
      after gastrointestinal operation, especially after gastrectomy. MRSA
      enterocolitis seems to occur when MRSA has first infected the naso-pharyngeal
      mucosa preoperatively, and then moved into the stomach, and subsequently
      proliferated in the higher pH gastric juices. The aim of this experiment was to
      reveal the relationship between the acidity of gastric juices and bacterial
      growth in the stomach during the pre and post operative period in an effort to
      prevent of MRSA enterocolitis. In vitro, MRSA was cultured for various periods at
      various pH values, and its proliferation was observed. MRSA did not grow in the
      culture at pH 1 at all, neither did it grow at pH 2 when cultured for more than 8
      hours. This data shows the germicidal effect of high acidity in the stomach.
      Clinically, twenty patients with cancer in the digestive tract had the bacteria
      in their gastric juices examined in terms of acidity before and after operation.
      In cases with an increased pH level in the gastric juices after the operation. S.
      aureus including MRSA, was isolated frequently from the stomach. In vitro,
      incubation of MRSA with gastric juices collected from those cases showed no
      development of MRSA when the pH was below 3.98. In order to prevent the onset of
      MRSA enterocolitis, the remnant stomachs of ten patients with stomach cancer were
      filled with hydrochloric acid lemonade just after operative
      reconstruction.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7829652
TI  - [Clinical study of scabies. The changes in the modes of transmission, and its
      diagnosis and treatment].
AB  - Scabies has become a common disease, not sexually transmitted but transmitted in
      households. Although it is also known to cause an epidemic in hospitals for the
      aged patients or residential homes, no effective treatment was taken for it at
      the present time. From January 1985 to December 1992, 424 patients with scabies
      (249 males and 175 females) visited the Dermatological clinic of Nippon Medical
      School Main Hospital. In these cases, only 13 patients (3.1%) were recognized as
      having STD. The sources of infestation were unclear in most cases where the
      disease was transmitted in households, which account for 38.5% of the patients.
      In 68 cases (16.0%), outbreaks of scabies in hospitals and residential homes
      affected the patients as well as the staffs and their families. The number of
      scabies cases which were infested in hospitals is increasing yearly. It is
      speculated that the hospitals for the aged patients and residential homes are
      becoming the main source of scabietic infestation. Only 16.6% of the patients
      were previously diagnosed or suspected to have scabies by their family doctors.
      It seems that the diagnosis of scabies is extremely difficult for the general
      practitioner. A considerable number of the patients who had been diagnosed or
      suspected to have scabies changed their doctor or stop visiting them. This is
      because an appropriate treatment is not available in most of medical facilities.
      At the time of the first visit to our clinic, 93.6% of the patients was diagnosed
      or suspected to have scabies, and the mite was demonstrated in 63.2% of the
      patients. It is suggested that careful inspection of scabietic burrows and the
      skillful technique to demonstrate the mite are essential to establish the
      diagnosis of scabies. Atopic dermatitis was the most common diagnosis of the
      patients who were misdiagnosed at the first time and later turned out to have
      scabies. These patients did have atopic dermatitis besides scabies. After the
      treatment with benzyl benzoate with crotamiton, 70.3% of the patients were cured
      and up to 94.9% of the patients were over improved. We compared the therapeutic
      effect of phenothrin to that of benzyl benzoate. Benzyl benzoate had more
      antipruritic effect and a little more improvement of skin lesion than phenothrin.
      However, there was no significant difference between benzyl benzoate and
      phenothrin in the period of time until the skin lesion cleared. Phenothrin is
      considered to have an adequate therapeutic effect for scabies.

PMID- 7829653
TI  - [An industrial toxicological study on workers who synthesize aminophenol and
      anisidine from chloronitrobenzene].
AB  - Aromatic nitro- and amino-compounds (ANA) are notorious methemoglobin forming
      substances. From 1987 to 1993, the author surveyed the exposure level to ANA and
      health status of workers in a chemical industry where they synthetize nitrophenol
      and anisidine from chloro-nitrobenzene. The ANA exposure indicator was the diazo
      reaction positive substance in the worker's urine (Dz) and the biological effect
      of ANA was monitored through the methemoglobin concentration in the blood (MHb).
      The following results were obtained from the survey. 1. Both the Dz and MHb
      values tended to become lower between 1987 and 1993. 2. The MHb levels of the
      workers were a little higher than the control levels, and the difference between
      the values was statistically significant (p < 0.01); both levels were, however,
      within the normal range. 3. The MHb value was estimable from a mathematical
      model: MHb = (k1-k2/a) x DU x CH, where k1 and k2 were constants and a, DU and CH
      indicated the activity of glutathione S transferase in erythrocytes (GST), DZ in
      urine and blood hemoglobin concentration, respectively. The correlation
      coefficient of the multiple regression was statistically significant (R2 = 0.263,
      p < 0.01). This model suggests that the biotransformed fraction of ANA in the
      pulmonary uptake site, the lung, could not penetrate into erythrocytes or act as
      an MHb former. The model seemed to be consistent and valid when urinary DZ values
      were less than 1.0 (mg/mg creatinine) and MHb values were less than 2.0 (mg/ml
      blood). Thus, the upper limit of normal levels for MHb can be considered to be
      2.0 (mg/ml blood), or 12-1.6% of total hemoglobin in blood. 4. The significance
      of the uptake sites, i.e., lung, skin etc., was discussed with reference to the
      evidence obtained from the longshoremen cases, who were percutaneously exposed to
      chloronitrobenzene in 1984. 5. Hemolysate solutions from the blood of workers
      were applied to isoelectric focusing electrophoresis (IEF), and Hb species of
      different valencies were separated; intermediate MHbs, where the heme iron in one
      of the components of Hb, i.e., in the alpha or beta chain was oxidized and MHb
      where both the alpha and beta chain heme iron oxidized and Hb X and Y, were
      separated and easily discernible. The correlation matrix was calculated using the
      data relevant to IEF and other indicators; MHb estimated spectrophotometrically,
      GST activity of erythrocytes, Hb and urinary DZ vale. The statistical procedure
      of principal component analysis was applied to the matrix, and two major
      principal components were extracted from the calculation.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 7829654
TI  - [An evaluation of coronary artery lesions of Kawasaki disease and congenital
      heart disease using rotary three dimensional digital cardiovascular angiography].
AB  - Congenital heart disease and the coronary artery lesions of children suffering
      from Kawasaki disease were evaluated by cardiovascular angiography using a newly
      developed rotary three-dimensional digital angiography method, and the usefulness
      of the device was examined. This method enable the observation of lesions from
      144 directions within a 180 degree range depicting an image from optimal
      directions. In addition, the radiation exposure during one angiography was about
      one fifth of that of conventional cineangiography. With regard to the lesions of
      the coronary artery, identification of the localization of the stenotic lesions
      were made possible, especially at bifurcations, or the stenotic lesions
      overlapping with other bifurcations or coronary artery aneurysms as well as the
      structure at the ostium of the left and right coronary arteries, which were
      difficult to identify using conventional coronary artery angiography. For the
      case of patient ductus arteriosus or major aortopulmonary collateral artery
      (MAPCA), separation and imaging of the overlap with other blood vessels through
      the three-dimensional observation became possible. This method is effective for
      the evaluation of the site, direction and morphology of these arteries. With
      regard to stenosis of the right ventricular outflow tract, the morphology and the
      degree of stenosis could be evaluated more accurately than by conventional
      cineangiography. In addition, the images matched well with the operative
      findings. This method was also effective for the diagnosis and evaluation of the
      stenosis at the main pulmonary artery and stenosis of the bifurcation of the
      right and left pulmonary arteries overlapping with the main trunk of the
      pulmonary artery.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7829655
TI  - [Dobutamine stress body surface mapping in Kawasaki disease].
AB  - The dobutamine (DOB) stress body surface mapping tests were carried out to detect
      myocardial ischemia in 23 patients who had Kawasaki disease previously. Eight of
      23 patients (group A) had coronary stenosis of 75% or more diameter reduction in
      major coronary arteries without sufficient collateral flow, as shown by the
      coronary angiography, but without myocardial infarction. Nine patients (group B)
      showed no ischemic change exercised 201Tl myocardial scintigram. Six patients
      (group C) had myocardial infarction due to Kawasaki disease. ST segment potential
      mapping (0.04 sec after the J point in QRS) and ST-T Isointegral mapping were
      performed using CVM-3000 system (87 leads), and the following calculations were
      made: number of leads with horizontal or down-sloping ST depression of 0.10 mV or
      more, lasting 0.08 sec (nST); row number of the minimum lead in the Isointegral
      map (Imin); number of positive leads on the seventh row in Isointegral mapping (I
      7); number of positive leads on the first row in Isointegral mapping (I-1) and I
      7/I-1 ratio. Based on these calculations the criteria for detecting myocardial
      ischemia (nST < or = 2, Imin < or = 2, I-7/I-1 > or = 1) were created and their
      usefulness was tested using findings of coronary angiography and exercised 201Tl
      myocardial scintigram as the golden standard. For the diagnosis of ischemic
      lesion, the DOB stress body surface mapping test in group A had higher
      specificity (nST: 100%, Imin: 89%, I-7/I-1: 100% vs. 78%) and higher sensitivity
      (75%, 50%, 63% vs. 38%), than those by the Treadmill test, while ischemic changes
      were not detected in group C by this test. From these results it is concluded
      that it is useful in evaluating ischemic heart disease in children who can not
      perform Treadmill exercised test adequately.

PMID- 7829656
TI  - [Isolation and characterization of three rat adult type beta-globin genes].
AB  - In order to clarify the molecular basis of the heterogeneity of rat hemoglobins,
      two DNA clones containing the genes for adult type beta-globins were isolated
      from a rat genomic DNA library. The results obtained in the present experiments
      are summarized as follows. 1) Clone lambda Rg beta 59 contained the gene for an
      adult rat beta-major globin, II beta, while clone lambda Rg beta 45 contained the
      genes for two adult rat beta-minor globins, III beta, and O beta, respectively.
      2) The entire nucleotide sequences of these genes were determined, indicating
      that the genes are all composed of 3 exons and 2 introns, and code for 146 amino
      acid residues. The genes exhibited structural features typical to known expressed
      beta-like globin genes, implying that they are all functional. 3) The predicted
      amino acid sequences completely agreed with the amino acid sequences of II beta,
      III beta and O beta globins, respectively, which we isolated in a separate
      experiment. 4) Sequence comparisons of three rat globin genes with one another
      and with the known mouse beta-major and beta-minor globin genes showed the
      occurrence of interesting homologies between two species from evolutional
      aspects. 5) Southern hybridization analysis of the genomic DNA implies that a
      number of beta-like globin genes other than the present ones exist in the rat
      genome.

PMID- 7829657
TI  - Progression of bone disease without deterioration of hematological parameters in
      a child with Gaucher disease during low-dose glucocerebrosidase therapy.
AB  - Gaucher disease is the most prevalent lysosomal storage disease. Although the
      efficacy of the macrophage-targeted human placental glucocerebrosidase is well
      known, it is still difficult to develop definitive guidelines regarding the
      appropriate therapy schedule. We describe an 8-year-old Japanese boy with Gaucher
      disease who had avascular necrosis of the right femoral head without
      deterioration of hematological variables during low-dose enzyme replacement
      therapy (12-13 IU/kg). This case demonstrates that continuous normal
      hematological findings may not preclude progression of other aspects of Gaucher
      disease in some patients during enzyme replacement therapy.

PMID- 7829659
TI  - [Hormone replacement therapy on menopausal women].

PMID- 7829658
TI  - [Endocrine surgery. Series 4. Significance of screening for thyroid disorders by
      palpation during mass screening for breast cancer].

PMID- 7829660
TI  - [Advance in pathogenesis and treatment of cerebrovascular diseases].

PMID- 7829661
TI  - Use of lectin-FITC conjugates for observation of elastic fibers.

PMID- 7829662
TI  - Induction of MHC class II antigen expression on murine microglia by interleukin
      3.
AB  - The effects of various cytokines on MHC class II antigen expression were examined
      in murine microglia. Interleukin-3 (IL-3), as well as interferon-gamma (IFN
      gamma), induced MHC class II antigen expression on these cells. IL-3 additionally
      enhanced MHC class II antigen expression induced by IFN-gamma. The induction of
      MHC class II antigen expression by IL-3 was not mediated via IFN-gamma
      production, because the effect was not blocked by antibodies to IFN-gamma. In
      contrast, granulocyte-macrophage colony-stimulating factor (GM-CSF) did not
      affect the expression of MHC class II antigen on naive cells and down-regulated
      IFN-gamma-mediated induction of MHC class II antigen expression on microglia.
      Because IL-3 and GM-CSF are apparently produced in the central nervous system,
      MHC class II antigen expression on microglia may be regulated by these cytokines
      synthesized in the central nervous system.

PMID- 7829663
TI  - Pavlovian conditioning of morphine-induced alterations of immune status: evidence
      for opioid receptor involvement.
AB  - Prior work in our laboratory has shown that morphine's immunomodulatory effects
      can become conditioned to environmental stimuli that predict drug administration.
      These immune alterations include conditioned changes in natural killer cell
      activity, interleukin-2 production, and mitogen-induced lymphocyte proliferation.
      The present study examined the involvement of opioid receptor activity in the
      establishment and expression of conditioned morphine-induced alterations of
      immune status. During the training phase of the experiment, Lewis rats received
      two conditioning sessions during which a subcutaneous injection of 15 mg/kg
      morphine sulfate was paired with exposure to a distinctive environment. On the
      test day, animals were re-exposed to the distinctive environment alone prior to
      sacrifice. Saline or naltrexone (0.3, 1.0, 3.0 or 10.0 mg/kg) was administered
      during either the training or the test session. Administration of naltrexone
      prior to training antagonized the development of all of the conditioned
      alterations of immune status including changes in the mitogenic responsiveness of
      splenocytes, suppression of natural killer cell activity, and interleukin-2
      production by splenocytes. Naltrexone administration prior to testing also was
      effective in antagonizing the expression of a subset of morphine-induced
      conditioned alterations in immune status. Taken together, these studies indicate
      that opioid receptor activity is involved in the establishment of conditioned
      morphine-induced immune alterations, as well as in the expression of a subset of
      these conditioned alterations of immune status.

PMID- 7829664
TI  - Alteration in the level of interferon-gamma results in acceleration of Theiler's
      virus-induced demyelinating disease.
AB  - Intracerebral (i.c.) inoculation of susceptible strains of mice with Theiler's
      murine encephalomyelitis virus (TMEV) results in immune-mediated demyelination.
      We examined the role of interferon (IFN)-gamma in this virally induced
      pathogenesis. Intraperitoneal (i.p.) injection of susceptible mice with an IFN
      gamma-neutralizing monoclonal antibody (mAb), DB-1, resulted in a significantly
      accelerated onset of disease. The anti-IFN-gamma mAb-treated animals showed a
      strong delayed-type hypersensitivity (DTH) response to the virus similar to that
      of control mAb-treated animals. Treatment with anti-IFN-gamma mAb had no
      significant effect on the clinical course of disease. However, intracerebral
      administration of recombinant IFN-gamma significantly accelerated the onset of
      TMEV-induced disease, as well as enhanced TMEV-specific T cell proliferation and
      DTH responses. The enhancing effect of IFN-gamma was completely abrogated by
      simultaneous treatment with anti-IFN-gamma mAb. Collectively, our data suggest
      that the level of IFN-gamma plays a key role in the TMEV-induced inflammatory
      response and a perturbation of this balance may result in an alteration in the
      course of the demyelinating disease.

PMID- 7829665
TI  - Blood-borne interleukin-1 receptor antagonist crosses the blood-brain barrier.
AB  - Recent work has shown that interleukin-1 alpha (IL-1 alpha) and IL-1 beta are
      transported from blood to brain across the blood-brain barrier by a saturable
      system. Here, we show that the endogenous IL-1 receptor antagonist (IL-1ra)
      radioactively labeled with either 125I or 35S is also transported across the
      blood-brain barrier by a saturable transport system. Between 0.33 and 0.65% of an
      intravenous dose of labeled IL-1ra entered each gram of brain. The three
      cytokines inhibited each other's transport in a way suggesting that their
      elevated blood levels would tend to favor the entry of IL-1 beta at the expense
      of IL-1 alpha. High performance liquid chromatography confirmed that
      radioactivity entering the brain represented intact cytokine. Recovery of
      radioactivity from cerebrospinal fluid, an area without blood vessels, and from
      the parenchymal fraction of the cortex, and area without circumventricular
      organs, after capillary depletion confirmed that blood-borne IL-1ra gained entry
      into the brain. The transport system for IL-1ra appeared to be linked to that for
      IL-1 alpha and IL-1 beta, but was not affected by IL-2, IL-6, TNF alpha, or MIP-1
      alpha. The results show that IL-1ra circulating in the blood can cross the blood
      brain barrier to enter the central nervous system.

PMID- 7829666
TI  - Immunomodulating and anti-inflammatory properties of the sympatholytic compound 6
      hydroxydopamine.
AB  - The objective of this study was to analyse the anti-inflammatory and
      immunosuppressive properties of 6-hydroxydopamine (6-OHDA), a well known
      sympatholytic compound. Collagen type II arthritis, a T cell-dependent autoimmune
      disease, was significantly suppressed by a short-term administration of 6-OHDA at
      the time of the disease onset. Similar outcome was observed when in vivo models
      of T cell-dependent and independent inflammatory reactions were applied. In
      contrast, long-term pretreatment with 6-OHDA and hence efficient sympatholysis
      did neither affect the course of arthritis nor the outcome of T cell-dependent
      and independent inflammatory reactions. These findings, together with evidence of
      dose-dependent in vitro inhibitory effects of 6-OHDA on lymphocyte proliferation
      and differentiation, indicate that the anti-inflammatory features of this
      compound are mediated through a direct action on effector cells rather than by
      sympatholysis.

PMID- 7829667
TI  - Interleukin-1 alpha, but not interleukin-1 beta, is a co-mitogen for neonatal rat
      Schwann cells in vitro and acts via interleukin-1 receptors.
AB  - The culture of neonatal rat Schwann cells (SC) with unfractionated cytokines
      induces an increase in SC proliferation. Previous studies demonstrated that while
      incubation of SC with interleukin-1(IL-1) does not result in enhanced SC
      mitogenesis, a mixture of antibodies to IL-1 alpha plus IL-1 beta inhibits
      cytokine-induced proliferation. We undertook the current studies to: (i) confirm
      that neither isoform of IL-1 directly causes SC proliferation; (ii) determine if
      there is a difference in the effect of antibodies to IL-1 alpha versus IL-1 beta;
      and (iii) determine if IL-1 contribution to cytokine-induced proliferation of SC
      is mediated via IL-1 receptors. IL-1 alpha or IL-1 beta from several sources,
      over a wide range of concentrations, failed to induce SC proliferation.
      Polyclonal antibodies to IL-1 alpha from several suppliers and a monoclonal
      antibody to IL-1 alpha inhibited SC proliferation, whereas similar antibodies to
      IL-1 beta had no effect on cytokine-induced SC proliferation. Addition of excess
      IL-1 alpha to an incubation mixture of unfractionated cytokines plus anti-IL-1
      alpha abolished the inhibitory effect of the antibodies. Addition of IL-1
      receptor antagonist (IL-1 Ra) to unfractionated cytokines inhibited SC
      proliferation. Therefore, while neither IL-1 alpha nor IL-1 beta is a solitary
      mitogen for neonatal rat SC, IL-1 alpha but not IL-1 beta acts as a co-mitogen.
      Moreover, IL-1 alpha seems to exert its co-mitogenic effect via receptors for IL
      1.

PMID- 7829668
TI  - Lipopolysaccharides and leukotriene B4 induce independently regulated
      electrophysiological and immunological responses in cultured astrocytes.
AB  - Astrocytes play an important role in immunological processes within the central
      nervous system. They are able to produce cytokines like interleukin 6 (IL-6) and
      depolarize substantially after stimulation by lipopolysaccharides (LPS) or
      leukotriene B4 (LTB4). Therefore, we investigated the coupling between these
      immunological and electrophysiological processes. Amiloride (250 microM), a
      blocker of various Na+ transport systems, inhibited LPS (5 micrograms/ml)-induced
      depolarization, whereas the LPS-induced release of IL-6 was unaffected,
      indicating different intracellular regulatory mechanisms. LTB4 (1.0 microM)
      induced a depolarization of a similar degree but mediated by a different ionic
      mechanism and failed to induce a detectable IL-6 release. Dexamethasone (1.0
      microM) and cycloheximide (2.0 microM) specifically reduced LTB4-induced
      depolarization, while LPS-induced depolarization was unaffected, providing
      further evidence for different regulatory pathways. Neither the depolarization
      nor the immunological stimuli served as a proliferation signal. These data
      demonstrate that independent immunological and electrophysiological responses
      with specific intracellular regulation are evoked after stimulation with LPS or
      LTB4. With respect to functional disturbance of depolarized glial cells, e.g. in
      maintaining local ionic homeostasis, neuronal excitability may be affected
      indirectly and by this way account for the appearance of neurological symptoms
      during inflammatory CNS diseases.

PMID- 7829669
TI  - Immunomodulation of experimental autoimmune myasthenia gravis with linomide.
AB  - Linomide, a synthetic immunomodulator, increases natural killer (NK) activity and
      markedly activates several lymphocyte populations in both experimental animals
      and humans. It has been shown to ameliorate the autoimmune manifestations of
      lupus-like disease in MRL/lpr mice and the clinical and pathological signs of
      acute and chronic-relapsing experimental autoimmune encephalomyelitis (EAE) in
      SJL/J mice. We examined the effect of linomide (100 mg/kg/day; administered in
      drinking water) on rabbits and rats with experimental autoimmune myasthenia
      gravis (EAMG). Following immunization with Torpedo acetylcholine receptor (AChR),
      all control rabbits developed clinical signs of severe weakness and exhibited a
      decrement of muscle action potential upon repetitive stimulation. In contrast,
      mild signs of weakness appeared in only two of five linomide-treated rabbits,
      with EMG borderline positive in one of them. Booster immunization with Torpedo
      AChR induced severe relapse and death in two EAMG control rabbits, whereas the
      two linomide-treated animals remained free of myasthenic symptoms. The serum
      level of antibodies against both Torpedo and rat AChR were markedly suppressed in
      the linomide-treated animals. Similar inhibition of clinical signs of EAMG was
      observed in the EAMG rat model. Furthermore, the in vitro proliferative response
      of lymph node cells to Torpedo AChR and the purified protein derivative of
      Mycobacterium tuberculosis was significantly lower in the linomide-treated EAMG
      rats than in the controls. Linomide may constitute a new immunomodulating agent
      for the treatment of myasthenia gravis.

PMID- 7829670
TI  - Nuclear localization of anti-Hu antibody is not associated with in vitro
      cytotoxicity.
AB  - IgG fractions of sera containing anti-Hu antibodies or control sera were
      incubated with Hu-positive and Hu-negative cell lines. Anti-Hu IgG specifically
      localized in the nucleus of Hu-positive cells. Anti-Hu-positive and control sera
      were incubated with Hu-positive cells and human complement or peripheral blood
      mononuclear cells. Hu antibody caused neither complement-mediated lysis nor
      augmented antibody-dependent cell-mediated cytotoxicity. Anti-Hu IgG did not
      affect proliferation of Hu-positive cells. Anti-Hu antibodies may not play a
      direct role in tissue injury in patients with paraneoplastic
      encephalomyeloneuropathy and anti-Hu antibodies.

PMID- 7829671
TI  - Absence of central nervous system pathology in severe combined immunodeficiency
      mice intraperitoneally injected with peripheral blood lymphocytes from multiple
      sclerosis patients.
AB  - In order to reproduce some of the pathological features of multiple sclerosis
      (MS) we transplanted peripheral blood lymphocytes (PBLs) from seven patients with
      MS into the peritoneal cavity of 28 severe combined immunodeficiency (MS-SCID)
      mice. Seven SCID mice were also transplanted with PBLs from two healthy subjects
      (hu-SCID). Animals were sacrificed between 2 and 8 weeks after transplantation
      (a.t.). Polymerase chain reaction (PCR) using primers able to amplify the HLA-DQ
      alpha region showed presence of human cells in neural tissues of MS-SCID mice.
      Immunocytochemical analysis revealed the scattered appearance of human
      lymphocytes (mostly CD45RO+ T cells) in the meningeal space and choroid plexuses
      of MS-SCID brains. However, human lymphocytes were similarly found in brains of
      hu-SCID mice. Both groups of mice never showed signs or symptoms of neurological
      impairment. Our results indicate that the simple transplantation of lymphocytes
      from MS patients into SCID mice is not likely to produce an MS-like pathology.

PMID- 7829672
TI  - Viscosimetric effect of fibrinogen.
AB  - AIMS: To investigate the correlation between fibrinogen concentration and plasma
      and serum viscosity. METHODS: Measurements of paired plasma viscosity and serum
      viscosity were compared in 45 subjects with a considerable range of fibrinogen
      concentrations and serum viscosity. RESULTS: Plasma and serum viscosity
      correlated well with plasma fibrinogen in cases of normal serum viscosity, but
      not in cases of myeloma or macroglobulinaemia. When an exponential correlation
      between plasma and serum viscosity was used, fibrinogen showed a good correlation
      in both normal and abnormal conditions. CONCLUSIONS: There is an exponential
      correlation between plasma and serum viscosity which depends on the plasma
      fibrinogen concentration. This is in accordance with Arrhenius's formula for
      solutions of varying concentrations.

PMID- 7829673
TI  - Variable detection of myeloid antigens in childhood acute lymphoblastic
      leukaemia.
AB  - AIMS: To determine whether the use of different sources of anti-CD13 and anti
      CD33 monoclonal antibodies leads to discrepant results in childhood acute
      lymphoblastic leukaemia (ALL), which might contribute to the wide variation in
      the reported incidence of myeloid antigen expressing ALL in childhood. METHODS:
      Stored leukaemic cells from 10 children with previously defined myeloid positive
      ALL were examined. A range of commercially available anti-CD13 and anti-CD33
      monoclonal antibodies, directly conjugated with phycoerythrin or fluorescein
      isothyocyanate, or both, was used. Positively reacting cells were detected by
      flow cytometry. RESULTS: There was a noticeable discordance between the different
      commercial sources of antibody and between the two fluorochromes in their ability
      to detect myeloid antigens, as well as variation in the intensity of staining.
      For CD13, one antibody reacted with eight cases and another with only four.
      Similarly, CD33 was detected in all 10 cases by one antibody and in only three by
      another. CONCLUSIONS: The lack of any consistent pattern of results suggests that
      various commercial antibodies against the same CD antigen might recognise
      different epitopes and that the number of molecules per cell might vary from case
      to case. These observations partly explain the variation in reported incidence
      and the failure to establish the clinical importance of myeloid positivity, and
      they highlight the importance of standardisation in multicentre studies in which
      immunophenotypic data are collected.

PMID- 7829674
TI  - Which proliferation markers for routine immunohistology? A comparison of five
      antibodies.
AB  - AIMS: To determine the best of five antibodies for immunohistochemical assessment
      of growth fraction in formalin fixed, paraffin wax embedded tissues. METHODS:
      Sections from 100 recent, and 17 ten year old or over wax embedded blocks of
      normal and malignant tissues were immunostained with monoclonal Ki67, polyclonal
      Ki67, PC10, MIB1, and JC1. The antibodies were evaluated for specificity of
      nuclear versus cytoplasmic staining, cleanliness of background, and compared with
      the expected pattern of staining in normal tissues, defined immunohistochemically
      by monoclonal Ki67 antibody in frozen tissues or by tritiated thymidine uptake.
      RESULTS: No marker was ideal, but best results were obtained with MIB1 and
      polyclonal Ki67, followed by JC1, PC10, and monoclonal Ki67. CONCLUSIONS: For
      routine use, MIB1 or polyclonal Ki67 are the best proliferation markers in
      conventional histological preparations. The other markers tested cannot be
      recommended.

PMID- 7829675
TI  - Decreased mucosal interleukin-4 (IL-4) production in gut inflammation.
AB  - AIMS: To determine the prevalence of cells secreting interleukin-4 (IL-4) in the
      gut mucosa of children with chronic inflammatory bowel disease. METHODS:
      Mononuclear cells were isolated from intestinal biopsy specimens from control
      children (n = 10) and children with active inflammatory bowel disease (Crohn's
      disease n = 15, ulcerative colitis n = 9, indeterminate colitis n = 3).
      Spontaneous IL-4 production was then measured by SPOT-enzyme linked immunosorbant
      assay (ELISA) using a pair of non-competing anti-IL-4 monoclonal antibodies. The
      percentage of T cells in the isolated cells were also determined and the
      prevalence of IL-4 secreting cells calculated per 10,000 T cells. RESULTS: In
      control children the mean number of IL-4 secreting cells was 15.1 per 10,000 T
      cells. In Crohn's disease and ulcerative colitis the means were 5.3 and 5.2,
      respectively. In two children with indeterminate colitis numbers were also low.
      There was no difference in the percentage of T cells in the cell preparations
      isolated from each patient group. The reduction of IL-4 secreting cells in
      patients with Crohn's disease was not caused by steroids. CONCLUSIONS: In
      idiopathic inflammatory bowel disease IL-4 secreting cells are reduced in
      diseased mucosa.

PMID- 7829676
TI  - Liver lesions found at colectomy in ulcerative colitis: correlation between
      histological findings and biochemical parameters.
AB  - AIMS: To classify lesions discovered at colectomy in patients with ulcerative
      colitis; to assess the importance of histological findings by correlating them
      with biochemical parameters. METHODS: Liver tissue specimens taken at colectomy
      from 59 patients with chronic ulcerative colitis were studied using light
      microscopy. The findings were compared with results of biochemical liver function
      tests. RESULTS: Abnormal laboratory findings were found in 12 patients with liver
      histology consistent with primary sclerosing cholangitis. Non-specific reactive
      hepatitis was observed in six patients, eight had fatty liver, and three minor
      non-specific parenchymal changes. Twenty nine patients had normal liver
      histology. The highest cholestatic serum enzyme activities were seen in two
      patients with sclerosing cholangitis. Cholangiography in these patients also
      revealed changes in the extrahepatic bile ducts. However, identical histological
      changes were also present in patients with only slightly abnormal or even normal
      liver enzyme activities. CONCLUSION: Biochemical tests of liver function do not
      reliably indicate the extent or severity of bile duct damage in ulcerative
      colitis, the assessment of which requires liver biopsy.

PMID- 7829677
TI  - Post-infantile giant cell hepatitis: histological and immunohistochemical study.
AB  - AIM: To determine the composition of the inflammatory infiltrate and to check for
      the presence of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in nine cases
      of post-infantile giant cell hepatitis. METHODS: The clinical, serological, and
      histological features of the nine cases were reviewed. Immunohistochemistry was
      used on liver biopsy specimens from six cases to: (i) characterise the
      lymphocytic infiltrate; (ii) assess the monocyte/macrophage response; (iii)
      detect "activated" perisinusoidal cells; and (iv) detect CMV and EBV antigens.
      Electron microscopic examination was carried out in two cases. RESULTS: Four
      patients had serological features suggestive of autoimmune chronic active
      hepatitis; in the other five cases the aetiology was obscure. Two patients
      presented with neurological symptoms. Hepatitis resolved completely in one
      patient; two patients showed clinical improvement; and one remained stable.
      Cirrhosis developed in three patients, one of whom proceeded to liver
      transplantation, and three patients died. Portal inflammation was present in all
      cases and lymphocytic piecemeal necrosis in eight cases, but intra-acinar
      inflammation associated with hepatocyte necrosis was observed in only five cases.
      The inflammatory infiltrate was composed predominantly of T lymphocytes; an
      increase in monocyte/macrophage cells was also observed. Mallory bodies, often
      with associated neutrophilic infiltrate, were present in four cases, and
      bilirubinostasis was a feature in four cases. "Activated" perisinusoidal cells
      were present, especially in relation to areas of inflammation, necrosis, and
      fibrosis. There was severe fibrosis or cirrhosis in five cases. Paramyxoviral
      nucleocapsids were not seen in the two cases examined ultrastructurally.
      CONCLUSIONS: Post-infantile giant cell hepatitis should be viewed as a
      heterogeneous clinical and aetiological entity encompassing cases of hepatitis
      with extensive giant cell hepatocyte transformation.

PMID- 7829678
TI  - Fat necrosis presenting as obscure abdominal mass: birefringent saponified fatty
      acid crystalloids as a clue to diagnosis.
AB  - AIMS: To describe the birefringent saponified fatty acid crystalloids seen in
      pancreatic fat necrosis. METHODS: A histological review, including polarising
      microscopy, of three cases of subacute or subclinical acute pancreatitis was
      performed. Histochemical analysis using Nile blue sulphate for lipid,
      Holczinger's copper rubeanate for fatty acids, and Alizarin Red S for calcium was
      performed in one case. Scanning electron microscopy and x-ray energy dispersive
      spectroscopic micro-analysis were performed in two cases. Necropsy pancreatic
      tissue, surgical archival tissue from cases of pancreatitis, and pancreatic and
      adipose tissue permitted to autolyse together in the laboratory, were also
      examined. The autolysed tissue was also examined histochemically. Stained and
      unstained sections were mounted in DPX and Canada balsam. Surgical material
      showing traumatic fat necrosis was reviewed. RESULTS: In each of the three cases
      there were subtle clues to subclinical pancreatitis. In neither surgical case was
      the true nature of the mass apparent to the operator. Histological analysis in
      all cases showed ghost adipocytes containing numerous polarising crystalloids, as
      well as some basophilic debris. Microanalysis showed calcium but no other
      substantial heavy element signals. Histochemical analysis showed a labile, polar,
      acidic lipid and the crystalloids behaved as calcium salts of free fatty acid.
      The crystalloids were not seen in archival material mounted in Canada balsam. No
      crystalloids were seen in traumatic fat necrosis. CONCLUSIONS: Little recognised,
      strongly birefringent, saponified free fatty acid crystalloids occurring in
      pancreatic fat necrosis may survive routine processing, and can point to the
      origin of obscure mesenteric masses related to subclinical pancreatitis.

PMID- 7829679
TI  - Interobserver variation in the reporting of the histopathological grading of anal
      intraepithelial neoplasia.
AB  - AIM: To assess the consistency in the histological reporting of anal
      intraepithelial neoplasia (AIN) among experienced histopathologists. METHOD: One
      hundred anal biopsy specimens were retrieved from archival material at St Mark's
      Hospital, London and graded by five histopathologists according to criteria
      outlined by Fenger (six point scale, ranging from normal to invasive carcinoma).
      RESULTS: There was only moderate agreement among the pathologists, with
      unweighted k scores ranging from 0.09 to 0.48, and weighted k scores of 0.17 to
      0.60. CONCLUSIONS: There is considerable interobserver variation in the reporting
      of AIN. A simplified system of grading may help to abolish this.

PMID- 7829680
TI  - Serum placental-type alkaline phosphatase activity in women with squamous and
      glandular malignancies of the reproductive tract.
AB  - AIM: To investigate serum placental-type alkaline phosphatase (PLAP-type)
      activities in women with squamous and glandular malignancies of the reproductive
      tract using an immunoradiometric assay. METHODS: PLAP-type immunoreactivity was
      measured in 180 women with non-ovarian malignancies of the reproductive tract and
      the values were compared with those from 334 controls. The cases comprised 18
      vulval, nine vaginal, 103 cervical, 46 endometrial, and five fallopian tube
      cancers. RESULTS: Serum PLAP-type activities were no different from controls in
      patients with squamous cell tumours. Women with adenocarcinoma of the cervix,
      endometrium, and fallopian tube had increased values: women with endometrial
      cancer had a median value nearly four times greater than that of controls. There
      was no direct correlation between PLAP-type activities and stage of disease in
      patients with endometrial cancer, but values reverted to normal after treatment.
      CONCLUSIONS: Serum PLAP-type measurements are of no value in the management of
      patients with squamous cell tumours of the female reproductive tract. Raised
      activities can, however, be found in glandular tumours, in particular endometrial
      cancer where serum PLAP-type measurements may be of value in predicting
      remission.

PMID- 7829681
TI  - Clonal analysis of three morphologically distinct lymphomas occurring in the same
      patient.
AB  - AIMS: To determine whether three morphologically distinct lymphomas (mucosa
      associated lymphoid tissue (MALT) lymphoma, monocytoid B cell lymphoma, and large
      cell anaplastic lymphoma), which occurred in the same patient, were in fact three
      morphological variants of the same lymphoproliferative process. METHODS:
      Previously described methods of clonal analysis using the polymerase chain
      reaction (PCR) were used to determine the pattern of rearrangements of the
      immunoglobulin heavy chain gene and the T cell receptor beta and T cell receptor
      gamma chain genes in the three lymphomas. RESULTS: All three morphological
      entities had identical patterns of gene rearrangements. CONCLUSIONS: This finding
      confirms the association between MALT lymphoma and monocytoid B cell lymphoma,
      and also provides evidence that large cell anaplastic lymphoma may not only arise
      de novo but may also be an end stage morphological picture in lymphoma
      progression.

PMID- 7829682
TI  - Rapid and simple method for preparation of genomic DNA from easily obtainable
      clotted blood.
AB  - A method was developed for the preparation of genomic DNA from clotted blood that
      is usually discarded after extraction, for other laboratory tests. The method,
      which involves proteinase K digestion, salt/chloroform extraction and 90% ethanol
      precipitation of DNA from clotted blood, is rapid, simple, and easy because it
      does not impose an extra burden on the patient.

PMID- 7829683
TI  - Comparison of formalin and Bouin's reagent for fixation of coagulase negative
      staphylococcal biofilm.
AB  - Methodological modifications, particularly the use of different fixatives, may
      account for discrepancies between studies of the relation between virulence and
      biofilm production in vitro by isolates of coagulase negative staphylococci. The
      efficacy of formalin and Bouin's reagent for fixing coagulase negative
      staphylococcal biofilms in a microtitre tray assay was compared. The optical
      density of stained adherent growth by three strains was reduced by an average of
      20% following fixation with 10% formaldehyde compared with Bouin's reagent. This
      difference seemed to be mainly because of increased background staining and
      blackening of the biofilm when Bouin's reagent was used. Formalin fixation was
      also effective at identifying early and late biofilm production in adherence
      growth kinetic experiments with 10 coagulase negative staphylococcal clinical
      isolates.

PMID- 7829684
TI  - Evaluation of the Urotest AB antibacterial substance detection test.
AB  - The Urotest AB was used to detect antimicrobial substances in urine samples. Of
      1022 urine specimens evaluated, Urotest AB detected inhibitors in 38.9%. Of 159
      urine specimens from patients thought to be taking an antibiotic, inhibitors were
      detected in 80.5%. This test may help to explain culture negative urine samples
      from symptomatic patients, and could help elucidate treatment failures and the
      epidemiology of antibiotic resistance.

PMID- 7829685
TI  - Endocrine and cytokine changes during elective surgery.
AB  - Elective surgery was used as a model of severe non-thyroidal illness (SNTI) to
      study the inter-relation between changes in serum thyroid hormones, thyroid
      stimulating hormone (TSH), cortisol, and interleukin 6 concentrations. The study
      was designed to determine whether the expected interleukin 6 increases after
      surgery are the cause of decreased serum tri-iodothyronine (T3) concentration
      normally observed following severe trauma. Blood was sampled for 24 hours before,
      during, and for 48 hours after abdominal surgery under general anaesthesia in 11
      patients. Total T3 decreased 30 minutes after induction and continued to decrease
      at 24 hours. After a transient increase at 30 minutes, free T3 also decreased,
      and free thyroxine (T4) concentrations, other than a similar transient increase,
      did not change. TSH concentrations were increased at four hours and the nocturnal
      surge was suppressed. The increase in the serum interleukin 6 concentration was
      not observed until four hours. Cortisol concentrations were increased at 30
      minutes and peaked at four hours. Therefore, the early changes in thyroid
      hormones and TSH accompanying surgery do not seem to be caused by changes in
      interleukin 6 concentrations.

PMID- 7829686
TI  - Metabolic and environmental origins of volatile organic compounds in breath.
AB  - Although more than 200 volatile organic compounds (VOCs) have been identified in
      human alveolar breath, their origins are still mostly unknown. An attempt was
      made to determine whether the major VOCs in breath were derived from inside or
      outside the body--that is, were they products of metabolism or contaminants from
      the environment? The concentrations were measured of the 24 most abundant VOCs in
      the alveolar breath of 12 normal volunteers and also in the air they inspired.
      The polarity of the mean alveolar gradient (concentration in breath minus
      concentration in inspired air) was positive in 15 VOCs and negative in nine. The
      mean alveolar gradient varied from strongly positive (for example, 2,3,3
      trimethylpentane), consistent with a metabolite manufactured in the body, to
      strongly negative (for example, isoprene), consistent with ingestion of an air
      pollutant which was then catabolised in vivo or excreted via an extra-pulmonary
      pathway.

PMID- 7829687
TI  - Varicella zoster gastritis in a bone marrow transplant recipient.
AB  - A case is reported of a patient who had previously undergone autologous bone
      marrow transplantation for recurrent Hodgkin's disease. The patient developed a
      generalised vesicular skin eruption. The clinical diagnosis was of disseminated
      shingles. Herpes viral particles were identified within the vesicular fluid by
      electron microscopy and using a specific monoclonal antibody to varicella zoster
      virus (VZV), positive immunofluorescence was detected in scrapings from the base
      of a vesicle. Gastroscopy and biopsy were performed because of severe abdominal
      pain and vomiting. The histological features were of non-specific active
      inflammation. Despite the histological absence of viral inclusions electron
      microscopy of the gastric biopsy revealed the presence of intranuclear herpes
      viral particles with a diameter of 90-100 nm. VZV specific DNA was detected by
      the polymerase chain reaction in the gastric biopsy extract. The patient was
      treated with acyclovir and made a full recovery.

PMID- 7829688
TI  - The investigation of hypercalcemia.

PMID- 7829689
TI  - Virus infections in primary immunodeficiency.

PMID- 7829690
TI  - Cytomegalovirus infection in the gastrointestinal tract.

PMID- 7829691
TI  - Adenovirus pulmonary infections identified by PCR and in situ hybridisation in
      bone marrow transplant recipients.
AB  - AIMS: To investigate adenovirus pulmonary infections in bone marrow transplant
      (BMT) recipients. METHODS: Formalin fixed, paraffin wax embedded lung tissue was
      examined from 13 necropsy cases after BMT using PCR and in situ hybridisation to
      detect adenovirus DNA. The E1A region of the adenoviral genome was targeted for
      PCR. In situ hybridisation was performed only in the PCR positive cases. RESULTS:
      Of the 13 lung specimens analysed, nine cases were negative for adenoviral
      nucleic acid. Four (30%) PCR and two (15%) in situ hybridisation positive cases
      were found. In some of the patients there were clinical and pathological
      indications that some diseases might be associated with adenovirus infection-
      haemorrhagic cystitis (three cases); necrotising pneumonia (one case). In
      necrotising pneumonia in which no pathogenic agents had been shown by
      conventional histological study, the in situ hybridisation technique showed
      positive staining for adenovirus. In a patient who died of renal failure caused
      by adenovirus nephritis, both PCR and in situ hybridisation were positive in the
      lung as well as in the kidney, although no histological change was found. Two PCR
      positive cases lacked positive sites for adenovirus by in situ hybridisation.
      CONCLUSIONS: The combination of PCR and in situ hybridisation could be useful for
      diagnosing adenovirus infection of the lung in BMT recipients. These results
      provide a basis for exploring further the clinical use of PCR and in situ
      hybridisation to diagnose adenovirus infection.

PMID- 7829692
TI  - In vivo endogenous spore formation by Coxiella burnetii in Q fever endocarditis.
AB  - AIMS: To determine whether Coxiella burnetii, the aetiological agent of Q fever,
      undergoes endogenous spore-like formation, the crucial stage of the developmental
      cycle, in the infected cardiac valves of patients with chronic Q fever
      endocarditis. METHODS: Surgically removed valves from three cases of Q fever
      endocarditis were processed for electron microscopy. Sections were stained with
      potassium permanganate and uranyl acetate before being extensively examined by
      transmission electron microscopy. RESULTS: In all three cases endogenous spore
      like formation was seen in the infected cardiac valves. CONCLUSIONS: As the
      factors that govern sporogenesis in C burnetii are still largely unknown, it is
      uncertain how important are the implications of the discovery of endogenous spore
      like formation in Q fever endocarditis. However, this finding may add new
      dimensions to current thinking about the treatment of chronic Q fever.

PMID- 7829693
TI  - Effects of changes in acid base and calcium concentration on fasting serum
      insulin, proinsulin, and glucose concentrations.
AB  - AIMS: To test the hypothesis that alterations in acid base or calcium
      concentration may affect proinsulin processing or the insulin secretion
      mechanism. METHODS: Changes in proinsulin secretion or cleavage were assessed by
      measuring serum intact proinsulin and immunoreactive insulin concentrations in
      three models of acid base and calcium disturbance: (1) subacute changes in acid
      base status in six volunteers who received oral placebo, ammonium chloride, or
      sodium bicarbonate for three five day periods; (2) acute changes in calcium
      concentration in eight subjects who received 25 mmol oral calcium; (3) chronic
      changes in calcium concentration in seven patients with primary
      hyperparathyroidism and five with pseudohypoparathyroidism. RESULTS: Acid base
      changes were confirmed by rises in serum bicarbonate concentrations (p < 0.01).
      No changes in serum insulin, intact proinsulin, or the proinsulin:insulin molar
      ratio were found. Serum calcium concentrations increased (2.49 v 2.38 mmol/l; p <
      0.05) and parathyroid hormone concentrations decreased (1.1 v 1.9 pmol/l; p <
      0.01) two hours after acute calcium loading. There were no significant
      differences in serum glucose, insulin, or intact proinsulin concentrations.
      Fasting proinsulin concentrations were significantly lower in the
      hyperparathyroid group (1.1 v 2.1 pmol/l; p < 0.05) and increased significantly
      after parathyroidectomy (2.1 v 1.1 pmol/l; p < 0.05). CONCLUSIONS: The results
      indicate that subacute acid base changes do not affect proinsulin cleavage.
      Although acute calcium loading has no demonstrable effect, chronic hypercalcaemia
      may influence the mechanism of insulin secretion.

PMID- 7829694
TI  - Bilirubin, ferritin, D-dimers and erythrophages in the cerebrospinal fluid of
      patients with suspected subarachnoid haemorrhage but negative computed tomography
      scans.
AB  - AIM: To assess the diagnostic value of cerebrospinal fluid (CSF)
      spectrophotometry, cytology, ferritin, and D-dimer measurements in the
      investigation of suspected subarachnoid haemorrhage in patients with negative or
      equivocal computed tomography (CT) scans. METHODS: CSF specimens submitted for
      assessment of xanthochromia were examined for erythrophages using a cytospin
      preparation stained with Wright's stain, for ferritin using the Ciba-Corning
      Magic IRMA assay, D-dimers using the Dimertest 2 latex agglutination slide test,
      and for bilirubin by scanning spectrophotometry. The patients were divided into
      three groups for data analysis and the results compared with the existing
      methods, CT, and angiogram results. Final diagnoses were reviewed by a consultant
      neurologist. RESULTS: Thirty six patients were recruited. In those patients with
      confirmed subarachnoid haemorrhage CSF cytology had a low sensitivity and there
      were false negative results with both the D-dimer and ferritin assays. Eleven
      patients with a negative or equivocal CT scan underwent angiography, but only one
      aneurysm and no arterio-venous malformations or bleeding points were identified.
      In the patient with the aneurysm there was no laboratory evidence of subarachnoid
      haemorrhage. Six patients had CSF abnormalities detected by the special tests
      only and in none of these cases was subarachnoid haemorrhage confirmed. All
      results were normal in four out of five cases of traumatic tap. CONCLUSIONS: This
      is a small study, but it shows that, depending on the timing of the lumbar
      puncture, false negative results can occur with both ferritin and D-dimer
      measurements. It suggests that neither of these tests adds significantly to the
      information provided by CT, visualisation of CSF, and spectrophotometry and
      confirms that, despite the use of spectrophotometry, D-dimer and ferritin assays
      in selecting patients for angiography, the proportion of patients with negative
      CT scans and colourless CSF with demonstrable vascular lesions remains low.

PMID- 7829695
TI  - PCR detection of HIV proviral DNA (gag) in the brains of patients with AIDS:
      comparison between results using fresh frozen and paraffin wax embedded
      specimens.
AB  - AIMS: To adapt the polymerase chain reaction (PCR) technique of HIV detection to
      paraffin wax embedded brain tissue and to compare the results with those obtained
      using frozen tissue. METHODS: HIV antigen and HIV proviral DNA were detected in
      specimens of frontal lobe using immunohistochemistry and PCR, respectively. DNA
      was extracted from fresh tissue using standard methods whereas the technique for
      extracting DNA from paraffin wax embedded tissue was partly modified. RESULTS:
      Twenty cases were examined. HIV DNA was detected in 16 cases in frozen specimens.
      Of these, 15 were also positive when paraffin wax embedded material was analysed.
      CONCLUSIONS: This study shows that HIV proviral DNA can be detected in formalin
      fixed, paraffin wax embedded brain tissue by PCR. The results obtained from
      paraffin wax embedded specimens showed a similar degree of reliability to those
      from fresh frozen brain. Factors such as fixative, fixation time, and delay in
      performing post mortem examinations did not seem to influence PCR amplification
      as positive results were obtained with specimens left in fixative for up to eight
      months, as well as in cases where post mortem examinations had been delayed for
      up to four days.

PMID- 7829696
TI  - Timed sequential analysis of creatine kinase in the diagnosis of myocardial
      infarction in patients over 65 years of age.
AB  - AIM: To assess the value of timed sequential analysis of creatine kinase (CK)
      activity for the early diagnosis of acute myocardial infarction (AMI) in patients
      over 65 years of age. METHOD: Samples were collected on admission and eight to 12
      hours later from 156 patients over 65 years of age. Routine cardiac enzyme
      activities were determined and serial electrocardiograms (ECGs) recorded. The
      predictive value of timed samples for CK activity, standard cardiac enzyme
      activities, and ECGs was compared with the final diagnosis on discharge. RESULTS:
      Forty one patients had a discharge diagnosis of AMI, 83 of angina pectoris, and
      the remaining 32 patients had other diagnoses. Electrocardiograms had a
      sensitivity of 55% and a specificity of 96%, giving a predictive value of 86% for
      a negative and 84% for a positive ECG. Standard cardiac enzymes had a predictive
      value of 99% for a negative result but only 68% for a positive result. The
      logarithm of the rate of change of CK activity had a predictive value of 97% for
      a negative result and 95% for a positive result. CONCLUSION: This study has shown
      that slope analysis of CK activity can be used for the early diagnosis of AMI in
      patients over 65 years of age, and that this was not affected by the presence of
      possible confounding diagnoses.

PMID- 7829697
TI  - Pathophysiology of HIV related thrombocytopenia: an analysis of 41 patients.
AB  - AIM: To analyse the pathogenic mechanism of HIV related thrombocytopenia.
      METHODS: Forty one patients with thrombocytopenia and HIV-1 infection were
      investigated over two years. Anticardiolipin antibodies were measured using an
      enzyme linked immunosorbent assay and antiplatelet antibodies were measured using
      an immunocapture technique. Tests for VDRL, C3 and C4, antinuclear antibodies and
      rheumatoid factor were also carried out in all patients and 80 control subjects
      (HIV-1 positive but non-thrombocytopenic). Indiumoxine labelled platelets were
      transfused in 13 patients. P24 antigen were also measured in 12 bone marrow
      aspirates. RESULTS: Antiplatelet antibodies and circulating immune complexes were
      found exclusively in the thrombocytopenic group; values for antiplatelet
      antibodies and circulating immune complexes were both higher in homosexual and
      bisexual patients. Three kinds of pattern were observed using 111 In-labelled
      platelets: splenic (n = 10); hepatic (n = 2); and destruction of bone marrow in
      just one case. The two most influential factors in the sequestration pattern were
      antiplatelet antibodies in the splenic uptake and circulating immune complexes in
      the hepatic and marrow sequestration. All patients, except three, had decreased
      platelet recovery. In those patients with a CD4 lymphocyte count of less than 200
      x 10(6) cells/l the recovery was clearly greater (53%) than in patients who had
      more than 200 x 10(6) /l (28%). Finally, in seven of the 12 patients who were
      chosen for immunohistochemical study, p24 antigen was detected in the
      megakaryocytes, verifying that HIV-1 infects such cells. CONCLUSIONS: The
      pathogenic mechanism of HIV related thrombocytopenia is probably multifaceted.
      Antiplatelet antibodies and circulating immune complexes would cause peripheral
      destruction in the spleen, liver, and bone marrow, in that order; and, on the
      other hand, there would be an ineffective immune thrombopoiesis and direct
      infection of the megakaryocytes which could cause a change in the function and
      maturity of these cells.

PMID- 7829698
TI  - Antibiotic prophylaxis in dermatologic surgery.
AB  - Antibiotic prophylaxis is generally administered either to prevent wound
      infection or to hinder the development of endocarditis. Although the use of
      antibiotics in certain circumstances to prevent wound infection can be
      straightforward, there are other circumstances in which the decision to use
      antibiotics is much less clear. Endocarditis prophylaxis has traditionally been
      based on the American Heart Association's guidelines, which do not cover
      dermatologic surgery. This article discusses the rationale and controversies
      surrounding the use of antibiotic prophylaxis for prevention of both wound
      infection and endocarditis, reviews the few studies that pertain to dermatology,
      and provides recommendations for antibiotic prophylaxis on a case-by-case basis
      for those who perform dermatologic surgery.

PMID- 7829699
TI  - Prepubertal acne: a cutaneous marker of androgen excess?
AB  - BACKGROUND: Early-onset acne before obvious signs of puberty is an uncommon
      phenomenon. OBJECTIVE: The aim of this study was to determine if prepubertal acne
      is associated with an excess of androgens. METHODS: Basal and
      adrenocorticotrophic hormone-stimulated plasma androgen levels were measured and
      bone age was determined in 15 children with early-onset acne. RESULTS: A late
      onset adrenogenital syndrome caused by 21-hydroxylase deficiency was diagnosed in
      two children. These children had early pubic hair development and advanced bone
      maturation. Heterozygosity for 21-hydroxylase deficiency was found in three other
      children. CONCLUSION: We recommend hormonal evaluation in children with
      prepubertal acne, especially those with associated advanced bone maturation and
      early pubarche.

PMID- 7829700
TI  - Cultivation of Borrelia burgdorferi from human tick bite sites: a guide to the
      risk of infection.
AB  - BACKGROUND: The risk of acquiring Lyme disease has been evaluated by
      xenodiagnostic procedures with laboratory strains of Borrelia burgdorferi and
      laboratory-reared Ixodes ticks, or by clinical trials in which diagnosis was
      based on clinical findings, culture, or serologic tests. OBJECTIVE: Our purpose
      was to determine the risk of infection from tick bites in a natural setting in
      which wild strains of B. burgdorferi were involved, by a biopsy culture
      technique. METHODS: Skin biopsy specimens were obtained from Ixodes scapularis
      tick bite sites, processed, and examined for the presence of B. burgdorferi.
      RESULTS: B. burgdorferi was cultivated from only 2 of 48 skin biopsy specimens.
      In both instances duration of tick attachment was approximately 24 hours.
      CONCLUSION: In a hyperendemic region for Lyme disease the risk of infection after
      a deer tick bite appears to be low, particularly if the tick has been attached
      for less than 24 hours.

PMID- 7829701
TI  - Use of a durometer to measure the degree of skin induration in
      lipodermatosclerosis.
AB  - BACKGROUND: Chronic lipodermatosclerosis is characterized by indurated skin on
      the medial aspect of the leg and is common around venous ulcers. The severity of
      induration of lipodermatosclerosis has been associated with poor ulcer healing.
      Clinical assessment of lipodermatosclerosis presently relies on a clinical skin
      severity score adapted from studies of patients with systemic sclerosis.
      OBJECTIVE: It would be desirable for prognostic reasons to develop an objective
      method for measuring skin hardness in lipodermatosclerosis. METHODS: The degree
      of skin induration at the midpoint between the upper and lower margin of
      lipodermatosclerosis in 30 sequential nonselected patients with
      lipodermatosclerosis was assessed by a blinded observer's clinical score and by
      quadruplicate determinations with a hand-held type O durometer. Skin induration
      on the medial aspect of the leg was similarly measured in five normal volunteers.
      Transcutaneous oxygen pressure was measured at the same sites. RESULTS: A direct
      linear relation (r = 0.962) was found between skin severity scores and durometer
      readings (p < 0.01). A clinical skin score of 2 reflected a higher durometer
      reading compared with a skin score of 1 (p = 0.0016) and, similarly, higher
      durometer readings were found in skin score of 3 compared with score 2 skin (p =
      0.0093). Transcutaneous oxygen pressure was uniformly reduced in
      lipodermatosclerosis (p < 0.02). CONCLUSION: The durometer is a reliable
      instrument for measuring skin hardness in patients with lipodermatosclerosis. It
      may be used to test the prognostic value of lipodermatosclerosis on ulcer
      healing.

PMID- 7829702
TI  - Pustular vasculitis of the hands.
AB  - BACKGROUND: Several patients were observed with a peculiar cutaneous eruption
      limited to the dorsa of the hands and fingers. Clinically the lesions had some
      resemblance to those seen in Sweet's syndrome, but biopsy specimens showed severe
      leukocytoclastic vasculitis. OBJECTIVE: Our purpose was to characterize this
      eruption clinically and histologically and compare it with previously described
      diseases. METHODS: Six patients observed since 1977 are described. Skin biopsy
      specimens were obtained. RESULTS: In six women (age, 41 to 79 years) a symmetric
      eruption of papules and plaques limited to the dorsa of the radial sides of the
      hands and first three digits developed. The lesions resembled those of Sweet's
      syndrome and were associated with fever, sterile culture, blood neutrophil
      leukocytosis, nonresponse to antibiotic therapy, and rapid response to
      prednisone. Biopsy specimens showed a severe leukocytoclastic vasculitis.
      CONCLUSION: These patients appear to have a distinct entity that we have termed
      pustular vasculitis of the hands.

PMID- 7829703
TI  - Papulonodular mucinosis associated with systemic lupus erythematosus: possible
      mechanisms of increased glycosaminoglycan accumulation.
AB  - BACKGROUND: The mechanism for the production of papulonodular mucinosis in
      patients with lupus erythematosus (LE) is not known. OBJECTIVE: Our purpose was
      to determine whether fibroblasts in a patient with LE and papulonodular mucinosis
      produced more mucin than normal fibroblasts and whether this mucin production
      could be stimulated by the patient's serum. METHODS: Skin fibroblasts from a
      patient with systemic LE and massive papulonodular mucin deposition, as well as
      normal fibroblasts, were incubated in the presence of serum from the patient or
      from a healthy volunteer. The production of glycosaminoglycan by fibroblasts was
      analyzed. RESULTS: Fibroblasts from the patient produced more glycosaminoglycan
      than did normal fibroblasts. Glycosaminoglycan production was increased in all
      cells when incubated in the presence of the patient's serum. CONCLUSION:
      Cutaneous mucin deposition in patients with papulonodular LE skin lesions is
      associated with increased glycosaminoglycan production by dermal fibroblasts. Our
      preliminary observations suggest glycosaminoglycan production by these
      fibroblasts appears to be stimulated by a factor, (or factors) in the patient's
      serum that is yet to be identified.

PMID- 7829704
TI  - Self-perceived sensory responses to soap and synthetic detergent bars correlate
      with clinical signs of irritation.
AB  - BACKGROUND: Epidemiologic studies indicate that after using soaps and other
      personal care products, many consumers experience irritation. In 50% of the cases
      the feelings of skin dryness, itching, and stinging occur in the absence of
      visible signs of irritation. OBJECTIVE: We sought to determine the relation
      between self-perceived sensory responses of panelists to cleansing products and
      clinical signs of irritation. METHODS: A combination of exaggerated arm-washing
      methods was designed to induce clinical signs of irritation with psychometric
      techniques developed to quantify sensations. RESULTS: Two studies demonstrated
      that panelists could reproducibly differentiate between products on the basis of
      the sensations they felt and that there was a significant correlation (frequently
      r > 0.80) between these and the observable signs. In the case of skin dryness
      panelists differentiated products several washing cycles before observable
      differences were detected. CONCLUSION: Sensory evaluations of irritation yield
      additional information on soap and detergent irritancy beyond clinical
      observations and expand understanding of the irritation process.

PMID- 7829705
TI  - London-born black Caribbean children are at increased risk of atopic dermatitis.
AB  - BACKGROUND: Previous reports suggest that atopic dermatitis is more common in
      black Caribbean children born in the United Kingdom than in white children. It is
      unclear whether these differences are caused by selection bias or variations in
      the use of the word "eczema" in the groups studied. OBJECTIVE: Our objective was
      to explore ethnic group differences in the prevalence of atopic dermatitis in
      London schoolchildren. METHODS: A cross-sectional prevalence survey of 693 junior
      school children in three schools was performed. Atopic dermatitis was defined in
      three ways: (1) by a dermatologist, (2) by visible flexural dermatitis as
      recorded by an independent observer, and (3) by a history of flexural dermatitis
      according to the child's parents. RESULTS: The prevalence of atopic dermatitis
      according to examination by a dermatologist was 16.3% in black Caribbean children
      and 8.7% in white children. This increased risk was present for different methods
      of defining of a atopic dermatitis and persisted after adjustment for potential
      confounders. CONCLUSION: London-born black Caribbean children appear to be at an
      increased risk of having atopic dermatitis.

PMID- 7829706
TI  - Doxycycline versus tetracycline therapy for Lyme disease associated with erythema
      migrans.
AB  - BACKGROUND: Doxycycline is widely used to treat Lyme disease associated with
      erythema migrans. Whether it is comparable to tetracycline is unknown. OBJECTIVE:
      We conducted a two-part retrospective analysis of (1) the safety and efficacy of
      doxycycline compared with tetracycline and (2) the safety and efficacy of a 14
      day versus a 20-day course of doxycycline. METHODS: Twenty-seven patients given
      tetracycline (500 mg four times a day for 14 days [group 1]) were compared
      retrospectively with 21 patients who received doxycycline (100 mg two or three
      times a day for 14 days [group 2]). The results for group 2 were also compared
      with that of 38 patients who received doxycycline for 20 days (100 mg three times
      daily) in a prospective treatment trial (group 3). RESULTS: There was no
      significant difference in the incidence of adverse drug effects or in efficacy at
      1 month, but at 1 year there was a trend toward a better outcome in the group
      treated with tetracycline (p = 0.08). A 14-day course of doxycycline was
      comparable to a 20-day course in the incidence of adverse drug effects and in
      clinical outcome. CONCLUSION: The principal advantage of doxycycline over
      tetracycline for the treatment of Lyme disease associated with erythema migrans
      is the convenience of less frequent dosing, not enhanced efficacy or safety.
      There appears to be no advantage in extending treatment with doxycycline from 14
      to 20 days.

PMID- 7829707
TI  - The minigrafting test for vitiligo: detection of stable lesions for melanocyte
      transplantation.
AB  - BACKGROUND: Selected patients with stable and refractory vitiligo may consider
      melanocyte transplantation as a therapeutic alternative. A method to anticipate
      the response to surgical repair is not available. OBJECTIVE: We evaluated the
      pigment spread of minigrafts when implanted within achromic lesions of stable
      vitiligo as a test to identify good candidates for surgical repigmentation.
      METHODS: Four to six minigrafts of 1.0 to 1.2 mm were implanted within lesions of
      patients with unilateral (localized) and bilateral (generalized) vitiligo.
      Pigment spread was assessed 3 months later. RESULTS: Forty-seven subjects were
      examined. In unilateral vitiligo 19 of 20 patients (95%) had a positive test
      result in comparison with only 13 of 27 patients (48%) with bilateral vitiligo (p
      = 0.002). CONCLUSION: The minigrafting test is a reliable tool to identify
      patients with stable vitiligo who may respond to melanocyte transplantation.
      Unilateral (localized) vitiligo is the best indication for surgical
      repigmentation.

PMID- 7829708
TI  - Surgical margins for excision of dermatofibrosarcoma protuberans.
AB  - BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) commonly recurs after standard
      surgical excision with a wide margin. No studies have been undertaken to
      objectively determine the appropriate surgical margins by measuring the extension
      of the subclinical tumor. OBJECTIVE: Our purpose was to measure the subclinical
      extent of tumor in 20 patients with DFSP to determine appropriate surgical
      margins. METHODS: We mapped the subclinical tumor extension with Mohs
      micrographic surgery and measured the surgical margins required to clear the
      tumor completely. RESULTS: We found that a 2.5 cm surgical margin through the
      deep fascia (nonscalp) or periosteum (scalp) cleared all of the tumors. DFSP
      tumors that measured less than 2 cm were completely cleared with a 1.5 cm
      surgical margin. None of our patients had a recurrence of the tumor, and in 16 of
      20 patients repairs were possible. CONCLUSION: Our data support the use of Mohs
      surgery to excise DFSP with maximum conservation of tissue and a high cure rate.

PMID- 7829709
TI  - Dye laser treatment of port-wine stains: comparison of the continuous-wave dye
      laser with a robotized scanning device and the pulsed dye laser.
AB  - BACKGROUND: Despite good results in the treatment of most port-wine stains (PWS)
      with continuous-wave visible-light lasers, light PWS and those in certain
      locations respond less favorably and have a higher risk of scarring. Robotized
      scanning devices such as the Hexascan device have been developed for continuous
      wave laser sources to produce greater target specificity, to increase
      reproducibility of results, and to decrease the incidence of adverse effects.
      OBJECTIVE: The purpose of this study was to compare the effects of the same
      wavelength of light (585 nm) on test sites within PWS with the flashlamp-pumped
      pulsed dye laser and a continuous-wave tunable dye laser scanned through a
      Hexascan robotized scanning device. METHODS: Two adjacent, noncontiguous sites
      within PWS were treated in 29 patients, one site with the flashlamp-pumped pulsed
      dye laser and the other with an argon-pumped continuous-wave tunable dye laser
      affixed to a Hexascan device. RESULTS: Twenty-eight patients completed the study.
      The pulsed dye laser was found to be superior to the continuous-wave dye laser
      with the Hexascan device in 45% of patients, whereas the continuous-wave tunable
      dye laser with the Hexascan device was considered superior in 15%. There was no
      difference in the remaining 40%. Undesirable side effects were infrequent with
      both treatments. There was no significant difference in hypopigmentation or
      atrophic and hypertrophic scarring, but hyperpigmentation was more frequent with
      the continuous-wave dye laser with the Hexascan device. CONCLUSION: Both the
      pulsed dye laser and continuous tunable-wave dye laser with the Hexascan device
      produce slight lightening after one treatment. The pulsed dye laser produces
      slightly greater lightening than the continuous-wave tunable dye laser with the
      Hexascan device 6 weeks after treatment of test areas within PWS in 40% of those
      treated. It also produced slightly less hypopigmentation and hyperpigmentation.

PMID- 7829710
TI  - Clofazimine: a review of its medical uses and mechanisms of action.
AB  - Clofazimine has been in clinical use for almost 40 years, but little is known of
      its mechanism of action. The primary indication for clofazimine is multibacillary
      leprosy, but it is useful in several infectious and noninfectious diseases, such
      as typical myocobacterial infections, rhinoscleroma, pyoderma gangrenosum,
      necrobiosis lipoidica, severe acne, pustular psoriasis, and discoid lupus
      erythematosus. Postulated mechanisms of action include intercalation of
      clofazimine with bacterial DNA and increasing levels of cellular phospholipase
      A2. Clinical experience, possible mechanisms of action, and side effects of
      clofazimine are summarized.

PMID- 7829711
TI  - On the nature of histologic observations: the case of the Spitz nevus.

PMID- 7829713
TI  - Lasers.

PMID- 7829712
TI  - From mercury to malaria to penicillin: the history of the treatment of syphilis
      at the Mayo Clinic--1916-1955.
AB  - Between 1916 and 1955 the Mayo Clinic became recognized as one of the premier
      institutions specializing in the treatment of syphilis. First under the direction
      of John H. Stokes (1916-1924) and later Paul A. O'Leary (1924-1953), its
      Department of Dermatology and Syphilology, together with the members of the
      Clinical Cooperative Study Group, oversaw the establishment of standardized
      methods for the administration of the existing arsenicals and the introduction of
      new therapies. Malaria therapy, heat therapy, penicillin, and oxytetracycline
      each represented important advances in the treatment of syphilis and were
      extensively evaluated. Two important ancillary benefits of syphilis treatment
      were the development of routine intravenous techniques, which would later prove
      invaluable for the administration of antibiotics and cancer drugs, and the
      establishment of large cooperative clinical trials, the first of their kind.
      Under the leadership of Stokes and O'Leary the department produced a stream of
      pivotal clinical research that contributed to the effective management of
      syphilis in the United States.

PMID- 7829714
TI  - Surgical pearl: hydrocolloid dressings for full-thickness skin grafts.

PMID- 7829715
TI  - Three cases of subungual glomus tumors with von Recklinghausen neurofibromatosis.

PMID- 7829716
TI  - Cutaneous manifestations of Pseudomonas infections in AIDS.

PMID- 7829717
TI  - Disseminated pyogenic granuloma developing after an exfoliative dermatitis.

PMID- 7829718
TI  - Targetoid hemangioma associated with pregnancy and the menstrual cycle.

PMID- 7829719
TI  - Acantholytic dyskeratotic epidermal nevus as a mosaic form of Darier's disease.

PMID- 7829720
TI  - Nasal cocaine abuse mimicking midline granuloma.

PMID- 7829721
TI  - Successful treatment of notalgia paresthetica with topical capsaicin: vehicle
      controlled, double-blind, crossover study.

PMID- 7829722
TI  - Long-term outcome of patients with interdigital tinea pedis treated with
      terbinafine or clotrimazole.

PMID- 7829723
TI  - Erythema multiforme induced by suramin.

PMID- 7829724
TI  - Enalapril-induced lichen planus-like eruption.

PMID- 7829725
TI  - Chemical peeling as adjuvant therapy for facial neurotic excoriations.

PMID- 7829726
TI  - Erythropoietic protoporphyria: the literature's confused counsel.

PMID- 7829727
TI  - Cyclosporine in the treatment of generalized granuloma annulare.

PMID- 7829728
TI  - Control of American dermatopathology through laboratory capitation.

PMID- 7829729
TI  - The effort to decapitate American dermatopathology.

PMID- 7829730
TI  - Treatment of blue nevi with the Q-switched ruby laser.
AB  - The common blue nevus is a benign, localized collection of dermal melanocytes. To
      date, removal required excisional surgery to eliminate pigment that usually
      extends into the reticular dermis. We report the successful long-term elimination
      of common blue nevi on the nasal skin of two patients whose lesions were treated
      with the laser emission of 694 nm energy from the Q-switched ruby laser.

PMID- 7829731
TI  - Phialophora verrucosa: a new cause of mycetoma.
AB  - A 29-year-old Thai woman had draining sinus tracts, tumefaction, and granules on
      the plantar aspect of the foot. Phialophora verrucosa was isolated from the
      lesion. P. verrucosa is a major agent of chromoblastomycosis, which is known to
      rarely cause subcutaneous phaeohyphomycosis. This dematiaceous fungus has not
      been previously reported to cause mycetoma. This case illustrates the clinical
      spectrum of disease of this fungus. The salient features of mycetoma and
      management options are presented.

PMID- 7829732
TI  - Reevaluation of a kindred with congenital absence of dermal ridges, syndactyly,
      and facial milia.
AB  - We observed a newborn infant of a previously reported kindred with absent dermal
      ridge pattern, syndactyly, and facial milia. The infant's features were
      consistent with three other kindreds, suggesting that this entity is a single
      disorder with variable expression. Furthermore, this entity should be considered
      in the differential diagnosis of excessive congenital facial milia and erosions.

PMID- 7829733
TI  - Extensive extraspinal hyperostoses after long-term oral retinoid treatment in a
      patient with pityriasis rubra pilaris.
AB  - We describe a patient with severe pityriasis rubra pilaris in whom extensive
      extraspinal hyperostoses developed after 13 years of oral retinoid treatment. The
      most prominent abnormality was a bridging exostosis between the left acetabulum
      and collum. X-ray examinations of the spine during retinoid therapy showed no
      abnormalities. During oral retinoid treatment, it is important to ask the patient
      on a regular basis about any skeletal pains or mobility restriction. Normal
      spinal x-ray results are no guarantee that a patient is free of hyperostoses.
      Discontinuation of acitretin therapy resulted in a severe exacerbation of the
      patient's pityriasis rubra pilaris after 2 weeks. The clinical response to
      administration of azathioprine was clearly inferior to that of acitretin.
      However, low-dose oral methotrexate therapy appeared to be a good alternative in
      this patient, with a clinical result comparable to acitretin and no side effects
      after 6 months of therapy.

PMID- 7829734
TI  - Normolipemic papular xanthomatosis in erythrodermic atopic dermatitis.
AB  - We describe papular xanthomatosis that progressively developed in a patient with
      long-standing erythrodermic atopic dermatitis and normal lipid metabolism and
      without an associated systemic disease. Light microscopy showed a lobulated
      aggregate of sometimes foamy histiocytes. Ultrastructurally, these histiocytes
      contained lipid inclusions and lacked features of Langerhans or epithelioid
      cells. Other granulomatous skin diseases such as tuberculosis, sarcoidosis, or
      foreign body granuloma were excluded by histologic study, polarizing microscopic
      examination, electron microscopy, and microbiologic investigations. Nevertheless,
      these xanthomas showed an antigen expression pattern similar to that found in
      noninfectious granulomas (CD1a-, MS-1-, CD11c+, MRP-8/-14+, 25F9+, RM 3/1+/-,
      CD36(+), indicating that normolipemic papular xanthomatosis may be reactive
      process and should not be included among the true cutaneous non-Langerhans cell
      histiocytoses.

PMID- 7829735
TI  - Autoimmune progesterone dermatitis.
AB  - Autoimmune progesterone dermatitis is a rare cutaneous disorder characterized by
      recurrent cyclic eruptions during the luteal phase of the menstrual cycle. We
      describe a woman with postpartum onset of a papulovesicular eruption. The
      possibility of autoimmune progesterone dermatitis was raised because of the
      cyclic nature of the outbreak. A reactive intradermal progesterone test confirmed
      the diagnosis. A review of individual case reports is also presented.

PMID- 7829736
TI  - Amelanotic lentigo maligna melanoma.
AB  - Only five cases of the amelanotic variant of lentigo maligna melanoma of the face
      have been reported. We describe an additional four patients observed within the
      past 5 years, suggesting a much higher incidence of this variant than previously
      suspected.

PMID- 7829737
TI  - Nodular scleroderma.
AB  - We describe a 40-year-old woman with systemic scleroderma who had hundreds of
      firm nodules that developed on the trunk and upper extremities during several
      months. We briefly review previously reported cases of this rare variant of
      scleroderma.

PMID- 7829738
TI  - Disseminated Fusarium solani infection.
AB  - Disseminated fungal infections commonly occur in immunocompromised hosts; Candida
      spp. are the most common. Fusarium spp., soil saprophytes once considered
      pathogenic only in plants, have emerged as serious pathogens in neutropenic
      patients with malignancies. We describe two patients, one with acute myelogenous
      leukemia and the other with metastatic breast cancer, in whom disseminated
      Fusarium solani infection developed. Both patients had neutropenia and fever when
      generalized, tender, erythematous papules developed; most of the papules had
      black necrotic centers. Despite aggressive therapy with antifungal agents and
      granulocyte-macrophage colony-stimulating factor, both patients died within 1
      month. Disseminated Fusarium infection can be a life-threatening condition in
      which skin lesions are frequently the initial sign. Early recognition and
      hematopoietic recovery offer the best chance for survival.

PMID- 7829739
TI  - Atypical pemphigus associated with monoclonal IgA gammopathy.
AB  - We describe a 60-year-old woman with atypical pemphigus and IgA-lambda monoclonal
      gammopathy. Histopathologic study of vesiculopustular lesions showed
      intraepidermal acantholytic and neutrophilic blisters. Direct immunofluorescence
      revealed intercellular IgG deposition with concurrent deposits of IgA and C3.
      Indirect immunofluorescence and immunoblotting studies revealed that the patient
      had circulating IgG anti-intercellular antibodies that recognized the 150 kd
      desmoglein (pemphigus foliaceus antigen) in bovine desmosome preparation.
      Immunoblot studies with human epidermal extract showed that the IgG of this
      patient exclusively reacted with the 140 kd protein (between the 150 kd human
      desmoglein and the 130 kd human pemphigus vulgaris antigen), the nature of which
      is currently unknown. The patient also had IgA anti-intercellular autoantibodies,
      which reacted with the desmoglein in the bovine desmosome sample but did not show
      any reactivity in human epidermal extract.

PMID- 7829740
TI  - Zosteriform zygomycosis.
AB  - We describe a patient with zygomycosis that resembled herpes zoster infection.
      The diagnosis was readily made with a potassium hydroxide preparation that
      revealed sparsely to non-septate hyphae. The patient responded to combination
      antifungal therapy with amphotericin B and fluconazole. The clinical response
      correlated with antifungal susceptibility test results.

PMID- 7829741
TI  - Systemic capillary leak syndrome.
AB  - Systemic capillary leak syndrome is a rare, severe disorder with a high mortality
      rate. It consists of the shift of fluid and proteins from the intravascular to
      the extravascular compartment with subsequent hypovolemic shock. We describe a 34
      year-old-woman who had several episodes of generalized edema that evolved to
      hypovolemic shock. During the acute phase, laboratory investigations revealed
      marked hypoproteinemia, leukocytosis, and high levels of hematocrit and
      hemoglobin. A paraprotein IgG kappa chain was detected. Although different
      therapeutic trials were used, the patient continued to have similar episodes and
      she died during an acute episode 2 1/2 years after the first symptom of this
      disorder. The cause of systemic capillary leak syndrome is unknown. The presence
      of a paraprotein IgG is frequent in this group of patients.

PMID- 7829742
TI  - A nonscarring sublamina densa bullous drug eruption.
AB  - The term bullous drug eruption connotes several heterogeneous diseases in which
      blisters occur as a complication of the administration of drugs. Blisters may
      occur in bullous erythema multiforme, fixed drug eruption, or severe dermatitis
      medicamentosa with blisters. The common denominator is thought to be a
      hypersensitivity reaction to a systemic medication. Nevertheless, little has been
      written about the blisters in these disorders, and neither common nor distinct
      pathogenic mechanisms have been proposed. We describe a patient who had a rapidly
      progressive bullous eruption that occurred within hours of receiving intravenous
      trimethoprim-sulfamethoxazole. Routine histologic study of lesional skin
      demonstrated subepidermal blisters. Transmission electron microscopy and
      immunomapping of various basement components revealed that the cleavage plane of
      the blister was well below the lamina densa. After healing of the blistering
      process, no scarring or milia formation was observed.

PMID- 7829743
TI  - Adult-onset xanthogranuloma appearing symmetrically on the ear lobes.
AB  - Clinical backgrounds of patients with adult-onset xanthogranuloma are somewhat
      different from those of patients with juvenile xanthogranuloma, but the
      histologic findings of both forms of the disease are identical. The lesions of
      the adult form are usually asymmetric. We describe a patient with adult-onset
      xanthogranuloma that appeared symmetrically on the ear lobes. This case suggests
      a possible role for mechanical stimuli (e.g., earrings) in the pathogenesis of
      adult-onset xanthogranuloma.

PMID- 7829744
TI  - Cutaneous infection caused by Curvularia pallescens: a case report and review of
      the spectrum of disease.
AB  - A 75-year-old woman being treated with prednisone and methotrexate had a 5.5 x
      2.2 cm ulcer on the leg. A biopsy specimen revealed suppurative, granulomatous
      dermal inflammation with necrotic areas of septate, branching hyphae containing
      brown pigment. Cultures grew Curvularia pallescens. Oral ketoconazole therapy was
      started and the lesion was excised. The site healed after multiple excisions and
      grafts, and ketoconazole therapy was stopped after 7 months. This is the first
      reported case of invasive cutaneous infection by C. pallescens.

PMID- 7829745
TI  - Hydroa vacciniforme-like lymphomatoid papulosis in a Japanese child: a new
      subset.
AB  - An 8-year-old Japanese girl had a 9-month history of a self-healing
      papulovesicular eruption on her face, scalp, and neck that resembled hydroa
      vacciniforme (HV). Histologically, there was a dense infiltration of small
      lymphocytic cells and scattered large atypical cells expressing CD30. Study of
      gene rearrangement showed no monoclonality in the infiltrating cells. To our
      knowledge, this is the second case of lymphomatoid papulosis with clinical
      features resembling HV. However, we also found descriptions in the literature of
      two other Japanese children with malignant lymphoma who both initially had
      clinical features resembling HV. These findings suggest that these cases of HV
      like disease constitute a subset of lymphomatoid papulosis that is highly likely
      to progress to malignant lymphoma.

PMID- 7829746
TI  - Lithium therapy associated with hidradenitis suppurativa: case report and a
      review of the dermatologic side effects of lithium.
AB  - Lithium is frequently used in the management of several psychiatric disorders
      including acute mania, bipolar (manic-depressive) disorder, and recurrent
      depression. We describe a patient in whom hidradenitis suppurativa developed
      while the patient was receiving lithium. The cutaneous side effects of lithium
      are reviewed. The most frequent are psoriasis, acneiform lesions, folliculitis,
      alopecia, and a maculopapular/macular eruption. Many of these side effects
      respond less readily to conventional therapy while the patient is receiving
      lithium.

PMID- 7829747
TI  - Encephalocraniocutaneous lipomatosis: an uncommon neurocutaneous syndrome.
AB  - We describe a 2 1/2-year-old girl with encephalocraniocutaneous lipomatosis. The
      dysmorphologic manifestations in the skull, brain, skin, and eyes associated with
      a normal karyotype suggested the diagnosis of this rare neurocutaneous syndrome.

PMID- 7829748
TI  - Concurrent chromoblastomycosis caused by Fonsecaea pedrosoi and actinomycetoma
      caused by Nocardia brasiliensis.
AB  - Chromoblastomycosis and mycetoma are chronic infections caused by the repeated
      traumatic inoculation of organisms into the skin and subcutaneous tissue.
      Chromoblastomycosis is caused by several dematiaceous (pigmented) fungi, occurs
      in tropical regions, and usually affects the lower extremities. The lesions may
      be nodules, plaques, or tumorous masses. Mycetomas are caused by either true
      fungi (eumycetes) or filamentous bacteria (actinomycetes); they also occur
      predominantly in tropical areas and most frequently affect the foot or leg.
      Typically there is a firm swelling with multiple sinus tracts that drain small
      granules. The treatment of these infections is difficult. Surgery, cryotherapy,
      heat therapy, and antimicrobial agents are used to treat chromoblastomycosis.
      Surgery and antimicrobial agents are used for treatment of mycetomas. This is the
      first report of concurrent infections caused by these agents.

PMID- 7829749
TI  - Once daily milking of dairy cows: relationship between yield loss and cisternal
      milk storage.
AB  - The proportions of milk stored in the gland cistern (cisternal) and within
      secretory alveolar tissue (alveolar) were determined for a group of ten cows in
      mid lactation, yielding approximately 20 kg milk/d. As a proportion of total
      milk, cisternal milk, measured at 8 h after milking, ranged from 0.09 to 0.53.
      Milking frequency was then reduced from twice daily to once daily on two
      occasions, first for 1 week and then, 2 weeks later, for 2 weeks. Milk yield was
      reduced during once daily milking in all cows, by an average of 22.8% during the
      first week (P < 0.001). The amount of decrease varied among cows in a way that
      was unrelated to pretreatment yield, but the immediate decrease was significantly
      and inversely correlated with cisternal milk proportion (r = 0.81, P < 0.01).
      When milking reverted to twice daily, yield recovered to a value not
      significantly different from pretreatment, and the degree of recovery was
      inversely related to cisternal milk proportion (r = 0.74, P < 0.01). With the
      exception of one cow, yield decreases correlated well between the two periods of
      once daily milking. When treatment weeks were disregarded, lactation persistency
      (the rate of decline in yield with time) was unaffected by once daily milking.
      The results show that the ability of individual cows to tolerate once daily
      milking is related to their cisternal storage characteristics; yield is reduced
      less in cows that store a greater proportion of their total milk production
      within the cistern.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7829750
TI  - Effect of milking interval on secretion rate and composition of camel milk in
      late lactation.
AB  - The effect of milking interval on secretion rates of milk and milk constituents
      was studied in four milking camels during late lactation. An interval of 4 h
      produced the highest milk secretion rate compared with 8, 12 and 16 h intervals,
      and rates tended to decline with increasing milking intervals. Secretion rates of
      organic (lactose, SNF, fat and protein) and inorganic milk constituents (sodium,
      potassium, calcium and magnesium) generally followed similar patterns of
      decreasing secretion with increasing milking intervals. Many of the values for
      different intervals were significantly different.

PMID- 7829751
TI  - Machine milking of dairy goats during lactation: udder anatomy, milking
      characteristics, and blood concentrations of oxytocin and prolactin.
AB  - Forty-four goats were milked and milk flow recorded without or with 1 min manual
      prestimulation in early, mid and late lactation. Ultrasound measurements of cross
      sections of the whole mammary gland were performed in a water bath. In additional
      experiments with 15 goats, milk flow was recorded and frequent blood samples were
      taken for the determination of oxytocin and prolactin concentrations. Milk yield
      increased from the first to the third lactation and decreased markedly during the
      course of lactation. Average and peak milk flow rates were closely related to the
      actual milk yield. The ultrasound cisternal area was 27.4 +/- 1.5% of the entire
      udder half cross section. Milking characteristics were scarcely different without
      or with prestimulation, although oxytocin was released within 30 s after the
      start of prestimulation, whereas oxytocin concentrations without prestimulation
      increased only after the start of milking. Concentrations of prolactin were
      higher during July and August than in April, and increased similarly with or
      without prestimulation during milking. In contrast to dairy cows, prestimulation
      and an opportune release of oxytocin during milking does not significantly
      influence the course of milk flow in goats, and this is probably because large
      amounts of cisternal milk allow milk ejection to be induced only after the start
      of milking without causing bimodal or otherwise reduced milk flow.

PMID- 7829752
TI  - Evaluation of the use of an artificial teat to measure the forces applied by a
      milking machine teatcup liner.
AB  - An artificial teat containing a force transducer was constructed to study the
      forces exerted by the liner on the teat during milking. The objective was to
      develop a method of comparing the action of different liners under a variety of
      different milking conditions. The rigid structure of the artificial teat did not
      provide an accurate representation of a real teat but deformable models used in
      the past have not proved practical. Initial tests of the teat showed that it gave
      repeatable results during calibration. When placed in a liner, however,
      repeatable results could not be obtained if the teat-liner interface was
      disturbed. The forces that were measured under simulated milking conditions
      varied with liner wall position and with time. There was a peak and trough prior
      to a stable asymptotic value being attained and a noticeable time lag behind
      pulsation chamber pressure. This technique can be used to compare liners when a
      reliable method of locating the artificial teat within the liner has been
      developed.

PMID- 7829753
TI  - Disulphide arrangement in bovine caseins: localization of intrachain disulphide
      bridges in monomers of kappa- and alpha s2-casein from bovine milk.
AB  - Naturally occurring monomeric kappa-casein and alpha s2-casein in bovine milk
      were purified by ion-exchange chromatography in order to localize potential
      intrachain disulphide bridges. Enzymic cleavage of the proteins followed by mass
      spectrometry and amino acid sequence analysis of cystine-containing peptides
      revealed the presence of an intrachain disulphide bond in both proteins.

PMID- 7829754
TI  - Secondary structures in beta-casein peptide 1-42: a two dimensional nuclear
      magnetic resonance study.
AB  - Two dimensional NMR spectroscopy was used to study the structure of a peptide
      composed of the N-terminal 42 amino acid residues of beta-casein. The peptide was
      obtained by enzymic cleavage using endoproteinase Asp-N. Complete sequence
      specific 1H NMR assignment was performed for the peptide at three Ca2+
      concentrations (0, 22 and 37 mM). The NMR results show that the peptide was
      highly flexible and adopted multiple conformations. No stable secondary
      structures were present; however, the peptide had some regions with non-random
      structure. The region between residues Leu16 and Asn27 adopted conformations with
      an increased contribution of alpha-helical structure, a so-called nascent helix.
      Two regions, Glu11-SerP15 and Lys29-Phe33 showed an increased population of
      conformations with extended structures. Addition of Ca2+ induced chemical shift
      changes for the backbone amide protons, especially around the phosphoserine
      region and around the suggested alpha-helical structure, indicating that the
      addition of Ca2+ stabilized the structure already present in the apo form of the
      peptide.

PMID- 7829755
TI  - Quantitation of trans fatty acids in milk fat using spectroscopic and
      chromatographic methods.
AB  - Trans fatty acids (TFA) formed during biohydrogenation by ruminant animals were
      quantified in cows' milk fat by means of Fourier transform i.r. (FTIR)
      spectroscopy. When samples were analysed as the derived methyl esters, a spectral
      subtraction technique resulted in TFA values that were not biased by the
      unspecific absorption of intact triacylglycerols or influenced by the shape of
      the trans band. Austrian milk fat samples contained 20-50 g TFA/kg. Results
      obtained by analysis of TFA as triacylglycerols compared favourably with those
      obtained by using methyl esters. The findings of the FTIR method were further
      substantiated by applying argentation chromatography in combination with
      capillary gas chromatography to the same set of samples. Besides trans monoenoic
      acids, non-methylene interrupted cis, trans octadecadienoic acids contributed
      significantly to the total trans content. Two novel TFA, trans-11, cis-15
      octadecadienoic and cis-9, trans-13 octadecadienoic acids, were identified in
      milk fat by means of their retention behaviour on argentation chromatography and
      gas chromatography as well as by an oxidative degradation procedure.

PMID- 7829756
TI  - Identification of Bacillus strains isolated from milk and cream with classical
      and nucleic acid hybridization methods.
AB  - A total of 529 bacterial strains have been isolated from milk and cream sampled
      at different sites in a dairy production plant under conditions selective for
      aerobic sporeforming bacteria. Identification with classical methods based on
      morphological, physiological and biochemical criteria showed Bacillus
      licheniformis to be the most frequently occurring Bacillus sp. The investigation
      also revealed 62 unidentified strains. Classical identification methods were time
      consuming (3-7 d), lacked specificity and--because of their dependence on
      phenotypic gene expression--sometimes produced ambiguous results. Consequently, a
      colony hybridization method developed for the identification of B. licheniformis
      strains and using nonradioactive labelled 23S rRNA targeted oligonucleotide
      probes was also used. Identification of B. licheniformis with both classical and
      hybridization methods revealed diverging identification results for 70 strains.

PMID- 7829757
TI  - Inhibitory effect of dairy products on the mutagenicities of chemicals and
      dietary mutagens.
AB  - The antimutagenic effects of uninoculated milk and milks cultured with
      Bifidobacterium or Lactobacillus strains towards the mutagenicity induced by two
      direct mutagens, 4-nitroquinoline N-oxide and 2-nitrofluorene, and three dietary
      indirect mutagens, aflatoxin B1, benzo(a)pyrene and quercetin, were investigated
      using the in vitro Salmonella typhimurium test. Each cultured milk sample and
      control milk had a significant antimutagenic effect, to an extent varying with
      the mutagen used. Uninoculated milk had a greater inhibitory effect than cultured
      milks towards dietary indirect mutagens.

PMID- 7829758
TI  - Effect of yogurt feeding on the small and large intestine associated lymphoid
      cells in mice.
AB  - The effect of giving yogurt supplements to BALB/c mice on the various gut
      associated lymphoid cells was studied. Animals were fed for 2, 5, 7 and 10
      consecutive days. The different lymphoid cell types were identified and counted
      by haematoxylin-eosin staining of histological slices. The numbers of cells
      secreting IgA, IgG and IgM and the numbers of T lymphocytes were determined by
      direct immunofluorescence. The degree of activation of the intestinal macrophages
      in the small intestine was assessed by measuring the beta-glucuronidase (EC
      3.2.1.31) released into the intestinal fluid, and also by a histochemical method.
      Throughout the feeding period, there were no histological alterations in the gut,
      but there was marked cell infiltration, mainly of plasma cells and lymphocytes.
      The number of macrophages on the small intestine increased significantly after
      feeding for 2 d, while the beta-glucuronidase activity was only slightly higher
      that of the controls. After a 7 d feeding period, the number of IgA secreting
      cells increased, while the values for cells secreting IgM and IgG and for T
      lymphocytes remained similar to those of the controls. The effect of giving
      yogurt on lymphoid cells associated with the large intestine was mainly on the
      numbers of IgA secreting B cells and T lymphocytes, with a marked increase during
      the whole feeding period in the latter type of cell. Since giving yogurt mainly
      enhanced the IgA secreting B cells in both small and large intestines, this
      increase would strengthen the host's defence mechanisms in the intestinal mucosa.
      Although the number of macrophages was increased, there was no enhancement in
      their activity, which might have harmed the host by producing an inflammatory
      response.

PMID- 7829759
TI  - Comparative study of the iron-binding strengths of equine, bovine and human
      lactoferrins.

PMID- 7829760
TI  - Influence of 1 alpha-hydroxycholecalciferol on calcium and phosphorus
      concentration in camel milk.

PMID- 7829761
TI  - Partial identification of peptides from the water-insoluble fraction of cheddar
      cheese.

PMID- 7829762
TI  - A Canadian multicentre placebo-controlled study of a fixed dose of brofaromine, a
      reversible selective MAO-A inhibitor, in the treatment of major depression.
AB  - In a 6-week double-blind study, 220 patients with major depression (mostly
      outpatients) were randomly assigned to receive a fixed dose of brofaromine 150 mg
      daily (n = 111) or placebo (n = 109) after a 1-week single-blind placebo washout.
      Except for the HAM-D sleep items, brofaromine was superior to placebo on measures
      of depression as determined by the four methods of assessing drug efficacy: (1)
      psychiatric symptom rating (HAM-D 17-item less the three sleep items); (2) self
      rating scale (Beck Depression Inventory); (3) Clinical Global Assessment of
      Efficacy; and (4) drop-out rate due to lack of efficacy. Most commonly reported
      adverse events with brofaromine were: headache, nausea, dizziness and sleep
      disturbance. Brofaromine was found to be an effective antidepressant, superior to
      placebo with a good tolerability profile.

PMID- 7829763
TI  - The Birleson Depression Self-Rating Scale (DSRS). Clinical evaluation in an
      adolescent inpatient population.
AB  - The Birleson DSRS, a depression self-rating scale for children, was evaluated in
      a group of adolescent psychiatric inpatients and a community-based group of
      adolescents. The DSRS was a valid measure of depression but slightly less
      powerful with these patients than with children. The DSRS might be a useful tool
      for screening of depressive symptoms, at least in clinical settings.

PMID- 7829764
TI  - TSH response to TRH and ECT.
AB  - In 31 female patients diagnosed according to DSM-III-R criteria as suffering from
      'functional' psychosis (e.g., major depression, schizophrenia, mania) TRH tests
      were administered before, during and after a course of electroconvulsive therapy
      (ECT) to investigate the effects of ECT on HPT (hypothalamic-pituitary-thyroid)
      axis as well as the predictive value of TSH response to TRH on treatment outcome.
      In 20 patients all three TRH tests were available; no significant changes in the
      mean TSH response were found over the course of ECT; however, a change towards
      blunted TSH response at the end of treatment was observed. The initial TSH
      response did not predict the treatment outcome.

PMID- 7829765
TI  - Cognitive dysfunctions in recovered melancholic patients.
AB  - Cognitive dysfunctions were studied in symptom-free patients suffering from
      Recurrent Depressive Disorder with melancholia. Their performances on a standard
      neuropsychological battery were compared with those of a healthy sample matched
      for age and educational level. Statistically significant differences were found
      in Immediate Visual Memory, Delayed Logical and Visual Memory, Paired Learning
      and Block Design. Results seem to indicate that the cognitive disfunctions are
      not likely to be only mnesic. All these data suggest that these disfunctions
      found in some melancholic depressives could not be state-dependent.

PMID- 7829766
TI  - Effects of hydrocortisone on brain 5-HT function and sleep.
AB  - The effects of hydrocortisone administration (20 mg, orally, twice daily) on the
      sensitivity of brain 5-HT1A receptors in healthy volunteers were studied using a
      buspirone challenge paradigm. The effects of hydrocortisone administration on
      sleep architecture were also studied. Hydrocortisone treatment significantly
      attenuated the hypothermic and cortisol responses to buspirone; however, the
      prolactin and growth hormone responses were unchanged. Hydrocortisone also
      decreased the amount of rapid eye movement sleep (REM). The ability of
      hydrocortisone to attenuate 5-HT1A receptor mediated hypothermia and decrease REM
      sleep is shared by certain antidepressant treatments and may be related to the
      effects of corticosteroids on mood.

PMID- 7829767
TI  - The impact of social cognitive variables on the initial level of depression and
      recovery.
AB  - Thirty-seven patients who fulfilled DSM-III-R criteria for Major Depressive
      Disorder were recruited for a double-blind controlled trial of Desipramine and
      placebo for 6 weeks. Data about social cognitive variables, including social
      adversities, investment in roles and goals, general social support and crisis
      support were collected. Crisis support had a moderating effect on the initial
      level of depression: the more crisis support the subjects had, the less depressed
      they were on recruitment. Initial level of depression, the experience of
      adversity and drugs all contributed significantly to recovery defined as Hamilton
      Rating for Depression less than 10 at week 6. When recovery was defined as
      Hamilton score halved or more than halved between week 2 and week 6, subjects'
      level of ideal emotional support, and whether they had experienced adversity in
      their most invested domains, contributed significantly to recovery, independent
      of any drug effects or the initial level of depression. The higher their level of
      ideal emotional support, the less was the chance of these subjects recovering.
      The findings of this study pointed to the importance of controlling for psycho
      social variables in studies of response to treatment.

PMID- 7829768
TI  - Lithium response and genetics of affective disorders.
AB  - The authors have carried out an investigation of psychiatric morbidity in
      families of patients who responded and failed to respond to long-term lithium
      treatment. The study included 121 probands with RDC primary affective disorders
      and 903 first-degree relatives and spouses. Seventy-one probands were responders
      and 50 were nonresponders to long-term lithium treatment. Extended to 20 years,
      the follow-up of patients and their families provided substantial information
      relevant for the diagnosis and reliable assessment of lithium response. The
      diagnoses were based on all available information, SADS-L interviews and RDC
      criteria. The principal statistical methods were survival analysis and Cox
      regression analysis. The results revealed a significantly higher frequency of
      bipolar disorder in the relatives of lithium responders (3.8% vs. 0%).
      Schizophrenia was more common in the families of nonresponders (2.4% vs. 0.3%).
      There were no significant differences in the rates of other psychiatric
      disorders. Both family history and the proband's diagnosis contribute
      independently to predicting response to long-term lithium.

PMID- 7829769
TI  - Neuroendocrine responses to intravenous L-tryptophan in obsessive compulsive
      disorder.
AB  - We studied the neuroendocrine responses produced by intravenous L-tryptophan
      (TRP) in 16 untreated patients with obsessive compulsive disorder (OCD) and 16
      matched healthy controls. The increase in plasma growth hormone seen following
      TRP was significantly greater in the OCD patients, while TRP-induced prolactin
      release did not differ from controls. Taken in conjunction with findings from
      other neuroendocrine studies the data suggest that some aspects of 5-HT1A
      neurotransmission may be increased in OCD. This increase may represent a
      compensatory change which promotes adaptation to stress in non-depressed OCD
      patients.

PMID- 7829770
TI  - Is dental practice science based?
AB  - This paper explores the thesis that the changing medical needs of dental
      patients, advances in biomedical research, and the confluence of the financing of
      medical and dental care will result in closer linkages between the medical and
      dental care delivery systems during the next century. Five trends have been
      documented in support of this thesis: the increasing number of elderly and their
      retention of teeth means there is a greater need for restorative dental care than
      in previous generations; the elderly have chronic diseases and are taking more
      medications; younger patients are presenting more frequently with infectious,
      systemic diseases such as HIV/AIDS. New scientific discoveries are opening new
      possibilities for patient care, which generate even higher expectations on the
      part of future consumers of medical and dental services. The health and fitness
      trend is not a fad; new knowledge regarding diet, nutrition, and exercise is
      identifying systemic risk factors related to common oral pathologies. Medical and
      dental educators are paying increased attention to the application of basic
      sciences to patient care. HMOs are increasing their market share of medical care
      delivery and expanding their services with preventive care and total patient
      care, including dental services. Data are provided documenting that dentists see
      these trends occurring in their private practices. The paper concludes that the
      application of advances in science and technology to oral health will improve the
      quality of dentistry. However, only new, effective preventive agents will
      decrease the cost of care, while improved diagnostics and restorative
      technologies could increase dental care costs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7829771
TI  - Concepts of modern risk assessment and management.
AB  - An emerging and increasingly complex array of environmental health concerns face
      dental practitioners in both the private and public sectors. These concerns are
      challenging and possibly threatening the traditionally inviolable dentist-patient
      relationship. Regulatory bodies, health risk experts, attorneys, and enthusiastic
      media are inserting themselves into the process. Essential assets for
      "successful" dental practitioners include enhanced expertise in basic science and
      technology, including the area of risk assessment, and development of broadened
      perspectives and skills for communicating with patients and the public.

PMID- 7829772
TI  - Communicating science to our patients and the public.
AB  - Communicating dental science, especially on issues of health and safety, is
      assuming increased importance in dental practice and in the relation of the
      profession to the public. Effective risk communication requires knowledge,
      balance and sensitivity to the concerns of our patients and the public. It is a
      skill that takes preparation, training and practice, and schools and professional
      organizations should be encouraged to include it in their educational programs.
      Presenting dental science to the public is a more difficult challenge than for
      the individual patient since there is no readily available site for exchange,
      such as the office, and no personally established relationship, credibility or
      trust. A larger cadre of trained spokespersons from the practice, public health,
      academic and research communities is needed, and more extensive multi-lingual and
      multi-cultural educational material should be made available for community
      outreach. Oral presentations to the public require different skills of both a
      verbal and nonverbal nature than for office communication or professional group
      presentation-and guidelines are offered.

PMID- 7829773
TI  - Professors and professionals: higher education's role in developing ethical
      dentists.
AB  - Both higher education and the dental profession must seek to develop dentists who
      can combine technical competence with sensitivity to ethical and social concerns.
      Dental education and the overall higher education experience should seek to
      produce a practitioner who continues to develop as an ethical professional
      through ongoing learning, experience, and reflection. In pre-professional
      education, this goal requires integration of disciplinary content with
      consideration of contemporary issues that often provide the context for
      clarifying values and ethical behavior. As the knowledge explosion continues to
      splinter higher education into specialties and subcategories, attention must be
      given to integrating the campus as a learning community that promotes an
      interdisciplinary focus on societal issues. Higher education faculty serve as
      models for students in demonstrating the responsibility to relate one's area of
      professional expertise to broader ethical and social concerns.

PMID- 7829774
TI  - Higher education and health professions education: shared responsibilities in
      engaging societal issues and in developing the learned professional.
AB  - Higher education and, in turn, health professions education are being buffeted by
      a multiplicity of external and internal forces. Issues related to fiscal
      constraints, higher education's crisis of values and the teaching/research and
      educational outcomes dilemmas are explored. The increasing accountability of
      higher education by its public, including measures of institutional effectiveness
      exacerbate these forces. Health professions education programs and their parent
      universities and colleges must take better advantage of their respective
      resources and become united around central educational paradigms and outcomes.
      The ability of higher education and health professions education to engage and
      connect to societal issues is critical to the appropriate education of the
      student and to institutional survival. By interweaving the philosophy and culture
      of the university or college setting in the fabric of health professions
      education and particularly dental education, an environment could be created that
      results in a true learning institution. That is, one in which students and
      faculty learn together in all settings. The outcomes of such engagement are
      shared responsibilities and the creation of the learned professional, one who is
      connected to the world and is not trapped by parochial knowledge. Thus, the
      continuum of health professions education transcends technical and cognitive
      achievement but addresses core societal values as well. This paper then explores
      some of the factors impacting upon higher education and assesses their influence
      on the nation's health professions schools, and, specifically, colleges of dental
      medicine.

PMID- 7829775
TI  - Dentistry & philanthropy: fortune favors the prepared.

PMID- 7829776
TI  - Profiles in professionalism: foundations for today. Harold Hillenbrand.

PMID- 7829777
TI  - Celebrating the Year of Oral Health: changing public expectation and challenges
      for the profession.
AB  - The year 1994 was designated as the Year of Oral Health by the World Health
      Organization. The remarkable progress in oral health achieved in the United
      States over the past several decades is cause for celebration; however, the gains
      have not been equitably distributed and many challenges remain if good oral
      health is to become a reality for all Americans. Members of the dental profession
      in general, and Fellows of the American College of Dentists in particular, have a
      responsibility to be aware of not only the health of our individual patients but
      also the oral health of the public as a whole. Many opportunities to improve
      dental practice on the individual and community level exist. By taking action to
      better meet the overall oral health needs of society, the dentist can increase
      professional satisfaction, improve the health of the public, and enhance the
      status of the dental profession.

PMID- 7829778
TI  - Mechanism of hemodynamic improvement by dual-chamber pacing for severe left
      ventricular dysfunction: an acute Doppler and catheterization hemodynamic study.
AB  - OBJECTIVES: This study was undertaken to determine the mechanism by which
      improvement in hemodynamic variables may occur with dual-chamber pacing in
      patients with severe left ventricular dysfunction. BACKGROUND: Dual-chamber
      pacing has recently been proposed as a therapeutic alternative for the relief of
      symptoms in patients with dilated cardiomyopathy. METHODS: Fifteen patients with
      severe left ventricular systolic dysfunction were studied acutely during
      atrioventricular (AV) sequential pacing at various AV intervals (60, 100, 120,
      140, 180 and 240 ms) with use of combined Doppler velocity curves and pressures
      obtained by high fidelity manometer-tipped catheters and thermodilution cardiac
      output. RESULTS: Neither cardiac output nor mean left atrial pressure was
      significantly different when hemodynamic variables in the baseline state were
      compared with those during AV sequential pacing at the various AV intervals in
      all patients. The patients were classified into two groups. In group I (eight
      patients with PR intervals > 200 ms on the rest 12-lead electrocardiogram),
      cardiac output was significantly increased when AV sequential pacing at the
      optimal AV interval to output was compared with that at the baseline state (3.0
      +/- 1.0 vs. 3.9 +/- 0.43 liters/min, p = 0.005) because timing of mechanical
      atrial and ventricular synchrony was optimized. In addition, left ventricular end
      diastolic pressure and duration of diastolic filling were increased, and
      diastolic mitral regurgitation was abolished. In group II (seven patients who had
      normal AV conduction at rest), cardiac output during AV pacing decreased from the
      baseline value without change in the diastolic filling period. CONCLUSIONS: Dual
      chamber pacing may improve acute hemodynamic variables in selected patients with
      dilated cardiomyopathy, mainly by optimization of the timing of mechanical atrial
      and ventricular synchrony. Reestablishment of the optimal diastolic filling
      period and abolition of diastolic mitral regurgitation may also contribute to
      hemodynamic improvement.

PMID- 7829779
TI  - Effect of long-term digoxin therapy on autonomic function in patients with
      chronic heart failure.
AB  - OBJECTIVES: This study was conducted to determine the effect of long-term digoxin
      therapy on autonomic function in patients with mild to moderate chronic heart
      failure. BACKGROUND: Chronic heart failure is characterized by increased
      sympathetic activity and decreased parasympathetic activity. Intravenous
      digitalis has been found to reduce sympathetic activity immediately in these
      patients, but whether short-term neurohormonal effects are sustained during long
      term oral therapy has not been assessed. METHODS: We determined sympathetic
      activity in 26 patients with heart failure by measuring plasma norepinephrine
      levels and parasympathetic activity from variables of heart period variability
      derived from 24-h ambulatory electrocardiographic Holter recordings obtained
      before and after 4 to 8 weeks of digoxin therapy. RESULTS: After digoxin therapy,
      plasma norepinephrine decreased significantly from a mean +/- SEM of 552 +/- 80
      to 390 +/- 37 ng/ml. In addition, the RR interval increased significantly from
      719 +/- 19 to 771 +/- 20 ms. High frequency power increased from 84 +/- 24 to 212
      +/- 72 ms2, and the root mean square of successive differences in RR interval
      increased from 20.3 +/- 1.8 to 27.0 +/- 3.4 ms, indicating a substantial increase
      in parasympathetic activity. Low frequency power, an index of baroreflex
      activity, was also significantly increased (239 +/- 80 to 483 +/- 144 ms2) by
      digoxin therapy. CONCLUSIONS: These results indicate 1) that long-term therapy
      with digoxin acts to ameliorate the autonomic dysfunction of patients with heart
      failure, and 2) that the short-term neurohormonal effects of digoxin are
      sustained during prolonged treatment with the drug.

PMID- 7829780
TI  - Differential effects of dobutamine and a phosphodiesterase inhibitor on early
      diastolic filling in patients with congestive heart failure.
AB  - OBJECTIVES: This study was designed to compare the influence of beta-adrenergic
      stimulation (dobutamine) and a selective phosphodiesterase inhibitor (MS-857) on
      left ventricular diastolic performance and Doppler transmitral flow velocity
      patterns in patients with congestive heart failure and to elucidate the
      mechanisms for changes in early diastolic filling induced by each agent.
      BACKGROUND: Both beta-adrenergic agonists and phosphodiesterase inhibitors act
      through the cyclic adenosine monophosphate pathway. However, it is controversial
      whether they have similar effects on diastolic performance. No previous studies
      have investigated the effects of these agents on Doppler-derived measurements of
      diastolic filling. We hypothesized that they would have different effects on
      early diastolic filling in patients with congestive heart failure. METHODS:
      Twenty patients with chronic congestive heart failure resulting from idiopathic
      dilated cardiomyopathy were randomized to receive intravenous infusion of
      dobutamine (5 micrograms/kg body weight per min, n = 10) or oral administration
      of MS-857 (15 mg, n = 10). Transmitral flow velocity patterns were obtained with
      simultaneous recordings of pressure-volume loops using a conductance catheter
      with a micromanometer tip before and after drug administration. RESULTS: Left
      ventricular filling pressure was reduced by both agents. Dobutamine decreased the
      time constant of isovolumetric relaxation and increased the difference between
      pulmonary artery wedge pressure at the peak of the v wave and left ventricular
      minimal pressure (10 +/- 3 to 12 +/- 4 mm Hg, p < 0.01) and peak early filling
      velocity (47 +/- 7 to 56 +/- 11 cm/s, p < 0.01). The diastolic pressure-volume
      relation showed a leftward shift in all patients. In contrast, MS-857 did not
      affect the time constant but maintained the pressure difference (9 +/- 3 to 8 +/-
      3 mm Hg, p = NS) and peak early filling velocity (50 +/- 7 to 49 +/- 12 cm/s, p =
      NS). The diastolic pressure-volume relation after MS-857 showed a downward shift
      in most patients. CONCLUSIONS: These results indicate that beta-adrenergic
      stimulation and phosphodiesterase inhibitors have different effects on early
      diastolic filling through different mechanisms in patients with congestive heart
      failure.

PMID- 7829781
TI  - Progression of aortic stenosis in 394 patients: relation to changes in myocardial
      and mitral valve dysfunction.
AB  - OBJECTIVES: This study reports the results of echocardiographic follow-up in a
      large cohort of patients with aortic stenosis and correlates the progression of
      aortic stenosis with changes in the degree of mitral regurgitation and left
      ventricular hypertrophy and systolic dysfunction. BACKGROUND: Progressive aortic
      stenosis often causes left ventricular dysfunction and mitral regurgitation.
      Doppler echocardiography has greatly assisted in the noninvasive evaluation and
      follow-up of aortic stenosis. Nevertheless, the longitudinal follow-up of
      patients with Doppler echocardiography for the progression of aortic stenosis and
      the significance of progressive ventricular hypertrophy and mitral regurgitation
      have not been reported. METHODS: Serial Doppler echocardiography was performed in
      394 consecutive patients with valvular aortic stenosis at baseline and after a
      mean follow-up period of 37 +/- 16 months. Mean and peak aortic gradients, aortic
      valve area, left ventricular systolic and diastolic diameters and percent area
      change (shortening fraction) were expressed as continuous variables, and systolic
      dysfunction, mitral regurgitation, ventricular hypertrophy and filling properties
      were tabulated as categoric variables using a semiquantitative grading system.
      RESULTS: Peak and mean gradients increased by an average of 8.3 and 6.3 mm
      Hg/year, respectively; end-systolic and end-diastolic diameters increased by 1.9
      and 1.6 mm/year, respectively; and aortic valve area decreased by 0.14 cm2/year
      during the follow-up interval (p < 0.001 for all), indicating progression of
      aortic stenosis and ventricular dilation. Patients in the lowest quartile of
      aortic valve area and highest quartiles of mean and peak gradients had the least
      change compared with those in the highest quartile of aortic valve area and
      lowest quartile of mean and peak gradients (p < 0.01 for all). Patients with more
      mitral regurgitation at follow-up than at baseline had higher mean percent
      increase in mean and peak gradients as well as more progression of ventricular
      dilation and worsening systolic function compared with those with stable or
      improving mitral regurgitation (p < 0.05 for all). Similarly, subjects with
      worsening left ventricular hypertrophy had larger mean percent increase in mean
      and peak gradients than those with stable left ventricular hypertrophy (p < 0.01)
      but maintained stable ventricular volumes and systolic function. There was no
      correlation between the amount of change in mean or peak gradients and degree of
      deterioration in systolic function. CONCLUSIONS: Aortic stenosis progresses
      predictably over time; however, systolic dysfunction is an inconsistent marker of
      the hemodynamic consequences of severe aortic stenosis. As an adaptive response
      to pressure overload, progressive hypertrophy appears to prevent ventricular
      dilation and development or worsening of mitral regurgitation. Conversely,
      progressive mitral regurgitation may be seen as a maladaptive consequence of
      increasing aortic stenosis.

PMID- 7829782
TI  - Quantitative arteriography of apparently normal coronary segments with nearby or
      distant disease suggests presence of occult, nonvisualized atherosclerosis.
AB  - OBJECTIVES: The aim of this study was to evaluate, using quantitative
      arteriography, whether the diameter of visually normal coronary segments might be
      influenced by the relative proximity of visually apparent disease. BACKGROUND:
      Severity of coronary artery lesions is commonly referenced against a presumed
      normal nearby coronary segment with the presumption that visually smooth segments
      are relatively free of atherosclerotic disease. METHODS: Angiograms from 136 male
      patients with focal coronary disease were examined, and visually normal segments
      in the proximal portions of the major vessels were identified for measurement of
      mean segment diameters. Normal segments with immediately adjacent disease were
      compared with normal segments with distal disease in the same vessel and compared
      with normal segments in vessels for which the only other visible disease was in
      distant vessels. Angiograms with entirely normal findings from 26 age-matched men
      with atypical chest pain were used as controls. Segments were measured after
      nitroglycerin administration by means of computer-assisted quantitation. RESULTS:
      Mean diameters of visually normal segments with distant disease were smaller than
      those of control segments (p < 0.05). Normal left main and proximal left anterior
      descending coronary artery segments in patients with disease within the same
      vessel were significantly smaller than normal segments in patients with distant
      disease (p < 0.05). Normal segments with immediately adjacent disease had smaller
      mean diameters than normal segments with distal disease in the same vessel (p <
      0.05). CONCLUSIONS: Visually normal coronary segments have progressively smaller
      lumen diameters, depending on the relative proximity of visible disease.
      Measurement of percent stenosis on the basis of the diameter of apparently normal
      adjacent reference segments can result in underestimation of coronary lesion
      severity.

PMID- 7829783
TI  - Multivariate predictors of intravascular ultrasound end points after directional
      coronary atherectomy.
AB  - OBJECTIVES: This study attempted to identify the clinical, angiographic,
      procedural and intravascular ultrasound predictors of directional atherectomy
      results assessed by intravascular ultrasound. BACKGROUND: Several angiographic
      and intravascular ultrasound variables have been associated with the outcome of
      directional coronary atherectomy. No study has incorporated both modalities into
      a predictive model. METHODS: One hundred seventy patients were analyzed using
      preintervention and postintervention intravascular ultrasound and quantitative
      angiography. Clinical and procedural variables were collected by independent
      chart review. Quantitative and qualitative angiographic analysis was performed by
      a core laboratory in blinded manner. Intravascular ultrasound was performed using
      a transducer-tipped catheter, rotating within a stationary imaging sheath, and
      withdrawn automatically at 0.5 mm/s. Clinical, procedural, angiographic and
      ultrasound variables were tested in a multivariate linear regression model.
      Dependent ultrasound variables included postatherectomy lumen cross-sectional
      area and percent cross-sectional narrowing (plaque plus media/external elastic
      membrane cross-sectional area) and, in a subgroup of 47 patients studied using
      volumetric analysis, percent plaque volume removal. RESULTS: By multivariate
      stepwise linear regression analysis, predictors of residual lumen cross-sectional
      area (correcting for reference lumen area) included arc of calcium and
      preatherectomy plaque plus media cross-sectional area; predictors of residual
      cross-sectional narrowing were arc of calcium, preatherectomy plaque plus media
      cross-sectional area and lesion length; and predictors of percent plaque volume
      removal were arc of calcium and atherectomy device size. CONCLUSIONS: The
      preintervention lesion arc of calcium measured by intravascular ultrasound is the
      most consistent predictor of the effectiveness and results of directional
      coronary atherectomy.

PMID- 7829784
TI  - Coronary flow reserve assessment by dobutamine transesophageal Doppler
      echocardiography.
AB  - OBJECTIVES: This study attempted to determine the sensitivity and specificity of
      coronary flow reserve derived using transesophageal echocardiography for left
      anterior descending coronary artery stenosis. BACKGROUND: Transesophageal
      echocardiography can be used to measure coronary flow velocity and may provide a
      less invasive means of assessing coronary flow reserve. METHODS: Seventy-eight
      adult patients were studied by pulsed Doppler transesophageal echocardiography of
      the proximal left anterior descending coronary artery during a control period and
      peak (i.e., 40 micrograms/kg body weight per min) dobutamine infusion. Coronary
      flow reserve index was calculated as the ratio of maximal diastolic coronary
      velocity at peak dobutamine infusion to the control level and was considered
      abnormal if < 1.81. Two-dimensional transesophageal left ventricular views were
      obtained for analysis of wall motion. RESULTS: Coronary angiography showed > or =
      70% (group A, n = 18), 0% to < 70% (group B, n = 21) and no (group C, n = 39)
      left anterior descending coronary artery diameter stenosis. An abnormal coronary
      flow reserve index did not differ from a new regional wall motion abnormality in
      sensitivity for left anterior descending coronary stenosis in group A (15 [83%]
      of 18 vs. 15 [83%] of 18, p = NS) but was significantly more sensitive in group B
      (12 [57%] of 21 vs. 2 [10%] of 21, p < 0.025). The specificity for no left
      anterior descending coronary stenosis in group C between a normal coronary flow
      reserve index and no new regional wall motion abnormality did not differ (87% vs.
      97%, p = NS). CONCLUSION: Doppler coronary flow reserve and two-dimensional
      dobutamine transesophageal echocardiography are equally sensitive for the
      detection of left anterior descending coronary stenosis > or = 70% and equally
      specific. However, Doppler coronary flow reserve, compared with two-dimensional
      dobutamine transesophageal echocardiography, is more sensitive for intermediate
      left anterior descending coronary stenosis and may play a significant adjunctive
      role to cardiac catheterization and other noninvasive techniques for assessing
      coronary artery disease.

PMID- 7829785
TI  - Development and evaluation of the Seattle Angina Questionnaire: a new functional
      status measure for coronary artery disease.
AB  - OBJECTIVES: This study sought to establish the validity, reproducibility and
      responsiveness of the Seattle Angina Questionnaire, a 19-item self-administered
      questionnaire measuring five dimensions of coronary artery disease: physical
      limitation, anginal stability, anginal frequency, treatment satisfaction and
      disease perception. BACKGROUND: Assessing the functional status of patients is
      becoming increasingly important in both clinical research and quality assurance
      programs. No current functional status measure quantifies all of the important
      domains affected by coronary artery disease. METHODS: Cross-sectional or serial
      administration of the Seattle Angina Questionnaire was carried out in four groups
      of patients: 70 undergoing exercise treadmill testing, 58 undergoing coronary
      angioplasty, 160 with initially stable coronary artery disease and an additional
      84 with coronary artery disease. Evidence of validity was sought by comparing the
      questionnaire's five scales with the duration of exercise treadmill tests,
      physician diagnoses, nitroglycerin refills and other validated instruments.
      Reproducibility and responsiveness were assessed by comparing serial responses
      over a 3-month interval. RESULTS: All five scales correlated significantly with
      other measures of diagnosis and patient function (r = 0.31 to 0.70, p < or =
      0.001). Questionnaire responses of patients with stable coronary artery disease
      did not change over 3 months. The questionnaire was sensitive to both dramatic
      clinical change, as seen after successful coronary angioplasty, and to more
      subtle clinical change, as seen among outpatients with initially stable coronary
      artery disease. CONCLUSIONS: The Seattle Angina Questionnaire is a valid and
      reliable instrument that measures five clinically important dimensions of health
      in patients with coronary artery disease. It is sensitive to clinical change and
      should be a valuable measure of outcome in cardiovascular research.

PMID- 7829786
TI  - Effects of brain (B-type) natriuretic peptide on coronary artery diameter and
      coronary hemodynamic variables in humans: comparison with effects on systemic
      hemodynamic variables.
AB  - OBJECTIVES: This study attempted to clarify the effects of human brain (B-type)
      natriuretic peptide on coronary artery diameter and coronary vascular resistance
      in humans. BACKGROUND: Brain natriuretic peptide induces vasodilation in systemic
      circulation by activating particulate guanylate cyclase of the vascular smooth
      muscle. METHODS: In 13 patients with normal coronary arteries and left
      ventricular function, brain natriuretic peptide was infused at 0.5 microgram/kg
      body weight per min for 4 min into the left main coronary artery (six patients,
      Group A) or into the pulmonary artery (seven patients, Group B). Systemic
      hemodynamic variables and coronary sinus blood flow were measured before and
      after the infusion. The lumen diameter of the left coronary artery was
      quantitatively measured. RESULTS: In both groups, brain natriuretic peptide
      significantly increased heart rate and decreased mean arterial pressure. Rate
      pressure product remained unchanged in both groups. Brain natriuretic peptide
      decreased systemic vascular resistance index significantly in both groups (both p
      < 0.01 vs. baseline), and there was no difference in the effect between the
      groups. Brain natriuretic peptide decreased coronary vascular resistance in Group
      A (p < 0.01 vs. baseline) but did not affect coronary vascular resistance in
      Group B (p < 0.01 vs. Group A). The lumen diameters of the proximal and distal
      segments of the left coronary artery were increased significantly after brain
      natriuretic peptide in both groups. After infusion of brain natriuretic peptide,
      mean plasma level of brain natriuretic peptide in the coronary sinus increased
      from 36 to 130,411 pg/ml in Group A and from 64 to 12,329 pg/ml in Group B.
      CONCLUSIONS: Brain natriuretic peptide shows a vasodilator effect on the coronary
      artery system in humans. However, the effect does not appear uniformly but is
      seen preferentially in the epicardial coronary artery. The sensitivity of the
      coronary resistance vessels to brain natriuretic peptide is low compared with
      that of the resistance vessels of the systemic circulation.

PMID- 7829787
TI  - Intermittent transdermal nitrates do not improve ischemia in patients taking beta
      blockers or calcium antagonists: potential role of rebound ischemia during the
      nitrate-free period.
AB  - OBJECTIVES: This study was conducted to determine whether rebound ischemia occurs
      during nitrate-free periods with intermittent cutaneous nitroglycerin therapy in
      patients with angina pectoris who are receiving background antianginal therapy.
      BACKGROUND: Rebound angina has been suggested to be a complication of the nitrate
      free period with long-term cutaneous nitroglycerin therapy given intermittently
      to prevent tolerance. METHODS: Fifty-two patients with stable effort angina
      taking either a beta-adrenergic blocking agent (n = 25) or diltiazem (n = 22) or
      their combination (n = 5) completed a randomized, double-blind, placebo
      controlled crossover study of cutaneous nitroglycerin patches (50 mg). Active or
      placebo patches were worn for 1 week, applied at 8 AM and removed at 10 PM to
      provide a 10-h daily nitrate-free (or placebo-free) period. During the last 48 h
      of each study phase, a Holter monitor was used to detect ischemia. RESULTS: Only
      31 patients experienced ischemia during either phase of the study (23 during the
      patch-off period). A total of 463 ischemic episodes were recorded: 246 during
      placebo and 217 during nitroglycerin (p = 0.8, for per patient comparison). The
      majority (88%) of ischemic episodes were silent. Mean (+/- SEM) duration of
      ischemia during the total 48-h period was similar during active and placebo
      phases (35.5 +/- 15.0 min/24 h for active therapy vs. 29.7 +/- 9.8 for placebo, p
      = 0.8). This was due to an increase in duration of ischemia with active therapy
      during the patch-off period (46.9 +/- 17.9 min/24 h for active therapy vs. 22.5
      +/- 9.2 for placebo, p = 0.07) and a decrease during the patch-on period (27.5 +/
      14.0 min/24 h for active therapy vs. 34.5 +/- 11.0 min/24 h for placebo, p =
      0.16). The pattern of diurnal distribution of ischemic episodes differed between
      active and placebo phases. During placebo there was a nadir in the incidence of
      ischemia in the overnight patch-off period, with a significantly lower incidence
      between midnight and 6 AM (25 episodes) compared with the mean number of episodes
      during the three other 6-h periods (73 episodes, p < 0.001). During the
      nitroglycerin patch-off period, there was a loss of this overnight nadir, with
      the same incidence of ischemia between midnight and 6 AM (53 episodes) as the
      mean number of episodes for the three other 6-h periods (54 episodes).
      CONCLUSIONS: The majority of patients taking background antianginal therapy
      experienced no ischemia during the patch-off period. In the 44% of patients with
      ischemia during this period, there was a nonsignificant increase in the duration
      of ischemia with active therapy. Although this result was statistically
      inconclusive, the change in the distribution of diurnal ischemia offers
      suggestive evidence that rebound ischemia may be a problem with regard to
      intermittent cutaneous nitroglycerin.

PMID- 7829788
TI  - Enhanced insulin response relates to acetylcholine-induced vasoconstriction in
      vasospastic angina.
AB  - OBJECTIVES: This study investigated whether insulin response to an oral glucose
      load correlates to acetylcholine-induced coronary vasoconstriction in subjects
      with vasospastic angina. BACKGROUND: It has been suggested that coronary
      vasospasm is caused by augmented vascular responsiveness possibly exerted by
      atherosclerosis. Recently, insulin resistance syndrome has been proposed as a
      major promotor of atherosclerotic disease, potentially enhancing vascular smooth
      muscular tone. METHODS: Among subjects with angiographically smooth coronary
      arteries, we selected 14 subjects with vasospastic angina and 14 age- and gender
      matched subjects with atypical chest pain. We compared coronary vasomotor
      response to acetylcholine infusion, glucose and insulin responses to an oral
      glucose load (75 g), serum lipid concentrations, obesity, heart rate, blood
      pressure and smoking habits in both groups. RESULTS: Fasting serum insulin
      concentrations and insulin response were higher in subjects with vasospastic
      angina than in those with atypical chest pain; however, glucose tolerance,
      obesity, heart rate, blood pressure and smoking habits did not differ between
      groups. In subjects with vasospastic angina, nearly all coronary segments, except
      distal segments of the left circumflex coronary artery, were constricted at peak
      acetylcholine infusion (20 to 100 micrograms), whereas all segments were dilated
      in subjects with atypical chest pain. Regression analysis for both groups
      demonstrated a correlation between coronary vasoconstriction and fasting serum
      insulin concentrations (r = 0.52, p < 0.01), insulin response (r = 0.71, p <
      0.001), serum triglyceride concentrations (r = 0.51, p < 0.05) and atherogenic
      index (r = 0.44, p < 0.05). CONCLUSIONS: Results show that acetylcholine-induced
      coronary vasoconstriction in subjects with vasospastic angina correlates with
      hyperinsulinemia and enhanced insulin response, suggesting insulin resistance
      syndrome as a feature of vasospastic angina.

PMID- 7829789
TI  - Effect of high dose angiotensin-converting enzyme inhibition on restenosis: final
      results of the MARCATOR Study, a multicenter, double-blind, placebo-controlled
      trial of cilazapril. The Multicenter American Research Trial With Cilazapril
      After Angioplasty to Prevent Transluminal Coronary Obstruction and Restenosis
      (MARCATOR) Study Group.
AB  - OBJECTIVES: We conducted a randomized, double-blind, placebo-controlled trial to
      assess the effect of low and high dose angiotensin-converting enzyme inhibition
      with cilazapril on angiographic restenosis prevention after percutaneous
      transluminal coronary angioplasty. BACKGROUND: Angiotensin-converting enzyme
      inhibitors possess antiproliferative effects in animal models of vascular injury.
      However, a recent clinical trial using low dose cilazapril, a long-acting
      angiotensin-converting enzyme inhibitor, failed to prevent restenosis. METHODS:
      Patients received either cilazapril (1 or 2.5 mg in the evening after successful
      coronary angioplasty, then 1, 5 or 10 mg twice daily for 6 months) or matched
      placebo. All patients received aspirin for 6 months. Coronary angiograms before
      and after angioplasty and at 6-month follow-up were quantitatively analyzed. In
      addition, the clinical, procedural and angiographic factors associated with
      restenosis were determined with the use of stepwise logistic analysis. RESULTS: A
      total of 1,436 patients with a successful coronary angioplasty were recruited. As
      assessed by an intention-to-treat analysis, the mean difference in minimal
      coronary lumen diameter (mean +/- 1 SD) between the postangioplasty and follow-up
      angiogram at 6 months (primary end point) was -0.35 +/- 0.51 for the placebo
      group and -0.37 +/- 0.52, -0.45 +/- 0.52 and -0.412 +/- 0.53, respectively, for
      the 1-, 5- and 10-mg twice daily cilazapril groups (p = NS). Clinical events
      during follow-up did not differ among the four study groups. Multivariate
      analysis revealed only six variables as independent predictors of the loss of
      minimal lumen diameter: duration of angina < 6 months, history of myocardial
      infarction, minimal lumen diameter before and after angioplasty as well as a
      proximal lesion location and reference diameters. Traditional risk factors for
      atherosclerosis did not relate to restenosis. CONCLUSIONS: Long-term angiotensin
      converting enzyme inhibition with cilazapril in high as well as low dosages does
      not prevent restenosis and does not favorably influence the overall clinical and
      angiographic outcome after coronary angioplasty. Few factors are predictive of
      restenosis.

PMID- 7829790
TI  - Predictors of in-hospital and 6-month outcome after acute myocardial infarction
      in the reperfusion era: the Primary Angioplasty in Myocardial Infarction (PAMI)
      trail.
AB  - OBJECTIVES: This study examined the predictors of in-hospital and 6-month outcome
      after different reperfusion strategies in acute myocardial infarction.
      BACKGROUND: Thrombolytic therapy and primary angioplasty are both widely applied
      as reperfusion modalities in patients with myocardial infarction. Although it is
      accepted that restoration of early patency of the infarct-related artery can
      reduce mortality and salvage myocardium, the optimal reperfusion strategy remains
      controversial, and the predictors of outcome in the reperfusion era have been
      incompletely characterized. METHODS: At 12 centers, 395 patients presenting
      within 12 h of onset of acute transmural myocardial infarction were prospectively
      randomized to receive tissue-type plasminogen activator (t-PA) or undergo primary
      angioplasty without antecedent thrombolysis. Sixteen clinical variables were
      examined with univariate and multiple logistic regression analysis to identify
      the predictors of clinical outcome. RESULTS: By univariate analysis, in-hospital
      mortality was increased in the elderly, women, patients with diabetes and in
      patients treated with t-PA as opposed to angioplasty. Only advanced age and
      treatment by t-PA versus angioplasty independently correlated with increased in
      hospital mortality (6.5% vs. 2.6%, respectively, p = 0.039 by multiple logistic
      regression analysis). Similarly, the only variables independently related to in
      hospital death or nonfatal reinfarction were advanced age and treatment by t-PA
      versus angioplasty (12.0% vs. 5.1%, p = 0.02). The reduction in in-hospital death
      or reinfarction with angioplasty versus t-PA was particularly marked in patients
      > or = 65 years of age (8.6% vs. 20.0%, p = 0.048). Furthermore, primary
      management with angioplasty versus t-PA was the most powerful multivariate
      correlate of freedom from recurrent ischemic events (10.3% vs. 28.0%, p =
      0.0001). The independent beneficial effect of angioplasty on freedom from death
      or reinfarction was maintained at 6-month follow-up (8.2% vs. 17.0%, p = 0.02).
      CONCLUSIONS: In the reperfusion era, the two most powerful determinants of
      freedom from death, reinfarction and recurrent ischemia after myocardial
      infarction are young age and treatment by primary angioplasty.

PMID- 7829791
TI  - Quantitative angiographic comparison of elastic recoil after coronary excimer
      laser-assisted balloon angioplasty and balloon angioplasty alone.
AB  - OBJECTIVES: Coronary lumen changes during and after excimer laser-assisted
      balloon angioplasty were measured by quantitative coronary angiography, and the
      results were compared with the effects of balloon angioplasty alone. BACKGROUND:
      Reduction of atherosclerotic tissue mass by laser ablation in the treatment of
      coronary artery disease may be more effective in enlarging the lumen than balloon
      angioplasty alone. METHODS: A series of 57 consecutive coronary lesions
      successfully treated by xenon chloride excimer laser-assisted balloon angioplasty
      were individually matched with 57 coronary artery lesions successfully treated by
      balloon angioplasty alone. The following variables were measured by quantitative
      coronary analysis: 1) ablation by laser, 2) stretch by balloon dilation, 3)
      elastic recoil, and 4) acute gain. RESULTS: Matching by stenosis location,
      reference diameter and minimal lumen diameter resulted in two comparable groups
      of 57 lesions with identical baseline stenosis characteristics. Minimal lumen
      diameter before excimer laser-assisted balloon angioplasty and balloon
      angioplasty alone were (mean +/- SD) 0.73 +/- 0.44 and 0.74 +/- 0.43 mm,
      respectively. Laser ablation significantly improved minimal lumen diameter by
      0.56 +/- 0.44 mm before adjunctive balloon dilation. In both treatment groups,
      similar-sized balloon catheters (2.59 +/- 0.35 and 2.56 +/- 0.40 mm,
      respectively) were used. After laser-assisted balloon angioplasty, elastic recoil
      was 0.84 +/- 0.30 mm (32% of balloon size), which was identical to that after
      balloon angioplasty alone, namely, 0.82 +/- 0.32 mm (32%). Consequently, both
      interventions resulted in similar acute gains of 1.02 +/- 0.52 and 1.00 +/- 0.56
      mm, respectively. Minimal lumen diameter after intervention was equal in both
      groups: 1.75 +/- 0.35 and 1.75 +/- 0.34 mm, respectively. The statistical power
      of this study in which a 25% difference in elastic recoil (0.2 mm) between groups
      was considered clinically important was 95%. CONCLUSIONS: In matched groups of
      successfully treated coronary lesions, xenon chloride excimer laser ablation did
      not reduce immediate elastic recoil after adjunctive balloon dilation or improve
      the final angiographic outcome compared with balloon angioplasty alone using
      similar-sized balloon catheters.

PMID- 7829792
TI  - A prospective study of plasma fish oil levels and incidence of myocardial
      infarction in U.S. male physicians.
AB  - OBJECTIVES: This study evaluated whether increased intake of fish oils
      (eicosapentaenoic and docosahexaenoic acids) might reduce the risk of coronary
      heart disease. BACKGROUND: Observational and clinical studies have suggested that
      increased intake of fish oils, as reflected in plasma levels of fish oils, may
      reduce the risk of myocardial infarction. METHODS: A nested case-control study
      was conducted among the 14,916 participants in the Physicians' Health Study with
      a sample of plasma before randomization. Each participant with myocardial
      infarction occurring during the first 5 years of follow-up was matched by smoking
      status and age with a randomly chosen control participant who had not developed
      coronary heart disease. RESULTS: Mean levels of fish oils (with 95% confidence
      interval [CI] for paired differences and p values) in case and control
      participants, expressed as percent of total fatty acids, were, for
      eicosapentaenoic acid, 0.26 versus 0.25 (95% CI -0.03 to 0.05, p = 0.70) in
      cholesterol esters and 0.56 versus 0.54 (95% CI -0.04 to 0.09, p = 0.44) in
      phospholipids, and for docosahexaenoic acid, 0.23 versus 0.24 (95% CI -0.07 to
      0.04, p = 0.64) in cholesterol esters and 2.22 versus 2.14 (95% CI -0.10 to 0.27,
      p = 0.36) in phospholipids. Results adjusted for major cardiovascular risk
      factors showed a very similar lack of association between fish oil levels and the
      incidence of myocardial infarction. CONCLUSIONS: These results indicate no
      beneficial effect of increased fish oil consumption on the incidence of a first
      myocardial infarction. However, the effect of very high levels of fish oils could
      not be evaluated.

PMID- 7829793
TI  - Coronary artery bypass graft surgery after thrombolytic therapy in the
      Thrombolysis in Myocardial Infarction Trial, Phase II (TIMI II).
AB  - OBJECTIVES: We examined the results of coronary artery bypass graft surgery after
      thrombolytic therapy in the Thrombolysis in Myocardial Infarction trial, Phase II
      (TIMI II) with particular emphasis on patient characteristics, the impact of
      antecedent percutaneous transluminal coronary angioplasty and morbidity and
      mortality in certain subgroups. BACKGROUND: Coronary bypass surgery is frequently
      used after thrombolytic therapy, but there is relatively little information with
      regard to early and late outcomes. METHODS: We analyzed 3,339 patients enrolled
      in the TIMI II trial. Bypass surgery was performed in 390 patients (11.7%): 54
      (14%) within 24 h after entry into the trial or within 24 h of coronary
      angioplasty and 336 (86%) between 24 h and 42 days after entry. RESULTS:
      Perioperative mortality rates were, respectively, 16.7% and 3.9% (p < 0.001);
      perioperative myocardial infarction rates were 5.6% and 6.2%, respectively; and
      major hemorrhagic events occurred in 74% and 50.9%, respectively (p = 0.002). On
      multivariate analysis, the only independent predictor of perioperative mortality
      was bypass surgery within 24 h after entry or after coronary angioplasty. Among
      patients undergoing bypass surgery within 24 h of entry or after coronary
      angioplasty, the prevalence of multivessel disease (59.1% vs. 77.8%) and use of
      the internal thoracic artery (18.5% vs. 62.5%) were lower than in the remaining
      surgical patients. Among the 322 perioperative survivors, the 1-year mortality
      rate after discharge was only 2.2% and 1.9%, respectively, in the two groups.
      Only one patient had a documented recurrent myocardial infarction during the
      first year. CONCLUSIONS: The increased mortality rate with bypass surgery after
      thrombolytic therapy, particularly in patients undergoing operation within 24 h
      of coronary angioplasty or during the involving phase of infarction, must be
      balanced against the excellent 1-year prognosis and perioperative survivors, who
      are in general a group at higher risk of death or recurrent infarction. These
      data provide a basis for comparison for future studies.

PMID- 7829794
TI  - Incremental prognostic value of exercise thallium-201 myocardial single-photon
      emission computed tomography late after coronary artery bypass surgery.
AB  - OBJECTIVES: This study assessed the incremental prognostic value of exercise
      thallium-201 myocardial perfusion single-photon emission computed tomography
      (SPECT) performed > or = 5 years after coronary artery bypass surgery.
      BACKGROUND: Thallium-201 scintigraphy has shown significant prognostic value in a
      variety of populations with suspected and known coronary artery disease. However,
      its value in patients with previous bypass surgery remains unknown. METHODS: We
      studied 294 patients who were prospectively followed up. Cox proportional hazards
      models for prediction of "hard" events (cardiac death and nonfatal infarctions)
      were constructed, with variables considered for inclusion in hierarchic order:
      clinical and exercise data first, followed by scintigraphic information. RESULTS:
      Mean (+/- SD) follow-up duration after scintigraphy was 31 +/- 11 months. There
      were 20 cardiac deaths and 21 nonfatal acute myocardial infarctions. Twenty-nine
      patients had late (> 60 days after thallium-201 SPECT) revascularization
      procedures or underwent repeat bypass surgery or percutaneous transluminal
      angioplasty. Shortness of breath and peak exercise heart rate were the most
      important clinical predictors of hard events. Two scintigraphic variables added
      significant prognostic information to the clinical model: the thallium-201 summed
      reversibility score (summation of segmental differences between stress and
      redistribution scores) and the presence of increased lung uptake of the
      radiotracer. The global chi-square statistic for this model was twice as high as
      that for the clinical/exercise model alone (49.7 vs. 24.2). When a second
      multivariate Cox model was built adding "soft" events (i.e., late
      revascularization procedures) as outcomes of interest, the summed reversibility
      score was selected as an independent scintigraphic predictor of events. The
      global chi-square statistic for this model was 50.7, three times as high as that
      for the clinical/exercise model alone. CONCLUSIONS: After evaluation of treadmill
      and exercise data, thallium-201 myocardial perfusion SPECT provided incremental
      prognostic information in patients late after bypass.

PMID- 7829795
TI  - Outcome of cardiac surgery for carcinoid heart disease.
AB  - OBJECTIVES: The hypothesis was that cardiac surgery for symptomatic carcinoid
      heart disease in conjunction with adjunctive therapy could improve the long-term
      outlook of patients with carcinoid heart disease. BACKGROUND: Patients with
      carcinoid heart disease have a dismal prognosis; most die of progressive right
      heart failure within 1 year after onset of symptoms. Improved therapies for the
      systemic manifestations of the carcinoid syndrome have resulted in symptomatic
      improvement and prolonged survival in patients without heart disease. METHODS:
      Twenty-six patients with symptomatic carcinoid heart disease underwent valvular
      surgery. Preoperative clinical, laboratory, Doppler echocardiographic and
      hemodynamic factors were evaluated. The survival of the surgical group was
      compared with that of a control group of 40 medically treated patients. RESULTS:
      There were nine perioperative deaths (35%), primarily from postoperative bleeding
      and right ventricular failure. Of the 17 surgical survivors, 8 were alive at a
      mean of 28 months of follow-up. The postoperative functional class of the eight
      surviving patients was substantially improved. Late deaths were primarily due to
      hepatic dysfunction caused by metastatic disease. The only predictor of operative
      mortality (p = 0.03) was low voltage on preoperative electrocardiography (limb
      lead voltage < or = 5 mm). Predictors of late survival included a lower
      preoperative somatostatin requirement and a lower preoperative urinary 5-hydroxy
      indoleacetic acid level. There was a trend toward increased survival for the
      surgical group compared with the control group. CONCLUSIONS: Because new
      therapies have improved survival in patients with the malignant carcinoid
      syndrome, cardiac involvement has become a major cause of morbidity and
      mortality. Valve surgery is the only definitive treatment. Although cardiac
      surgery carries a high perioperative mortality, marked symptomatic improvement
      occurs in survivors. Surgical intervention should therefore be considered when
      cardiac symptoms become severe.

PMID- 7829796
TI  - Electrocardiographic identification of increased left ventricular mass by simple
      voltage-duration products.
AB  - OBJECTIVES: This study was conducted to validate the hypothesis that the product
      of QRS voltage and duration, as an approximation of the time-voltage area of the
      QRS complex, can improve the electrocardiographic (ECG) detection of
      echocardiographically determined left ventricular hypertrophy and to further
      assess the relative contribution of QRS duration to the ECG detection of
      hypertrophy. BACKGROUND: The ECG identification of left ventricular hypertrophy
      has been limited by the poor sensitivity of standard voltage criteria alone.
      However, increases in left ventricular mass can be more accurately related to
      increases in the time-voltage area of the QRS complex than to changes in QRS
      voltage or duration alone. METHODS: Standard 12-lead ECGs and echocardiograms
      were obtained for 389 patients, including 116 patients with left ventricular
      hypertrophy. Simple voltage-duration products were calculated by multiplying
      Cornell voltage by QRS duration (Cornell product) and the 12-lead sum of voltage
      by QRS duration (12-lead product). RESULTS: In a stepwise logistic regression
      model that also included Cornell voltage, Sokolow-Lyon voltage, age and gender,
      QRS duration remained a highly significant predictor of the presence of left
      ventricular hypertrophy (chi-square 26.9, p < 0.0001). At a matched specificity
      of 96%, each voltage-duration product significantly improved sensitivity for the
      detection of left ventricular hypertrophy compared with simple voltage criteria
      alone (Cornell product 37% vs. Cornell voltage 28%, p < 0.02, and 12-lead product
      50% vs. 12-lead voltage 43%, p < 0.005). Sensitivities of both the Cornell
      product and the 12-lead product were significantly greater than the 27%
      sensitivity of QRS duration alone (p < 0.01 vs. p < 0.001), the 20% sensitivity
      of a Romhilt-Estes point score > 4 (p < 0.001) and the 33% sensitivity of the
      best-fit logistic regression model in this cohort (p < 0.05 vs. p < 0.001).
      CONCLUSIONS: QRS duration is an independent ECG predictor of the presence of left
      ventricular hypertrophy, and the simple product of either Cornell voltage or 12
      lead voltage and QRS duration significantly improves identification of left
      ventricular hypertrophy relative to other ECG criteria that use QRS duration and
      voltages in linear combinations.

PMID- 7829797
TI  - Should echocardiography be performed to assess effects of antihypertensive
      therapy? Test-retest reliability of echocardiography for measurement of left
      ventricular mass and function.
AB  - OBJECTIVES: The purpose of this study was to determine the test-retest stability
      of echocardiography for the measurement of left ventricular mass and function in
      patients with hypertension. BACKGROUND: Determination of changes in left
      ventricular mass may be impaired by study variability. The amount by which
      variables of mass and left ventricular function must change in an individual
      patient to exceed temporal variability has not been determined in a multicenter
      trial. METHODS: Ninety-six patients with hypertension had two-dimensional
      targeted, M-mode Doppler echocardiography repeated at 6 +/- 8 days by the same
      technician utilizing the same machine. Left ventricular mass and variables of
      systolic and diastolic function were measured. Test-retest reliability and the
      width of the 95% confidence intervals of variable change, as well as the
      contributions of age, study quality and body size to measurement reliability,
      were determined. RESULTS: Despite excellent reliability (intraclass coefficient
      of correlation 0.86), the 95% confidence interval width of a single replicate
      measurement of left ventricular mass was 59g, exceeding usual decreases in mass
      during treatment. Study quality, which was dependent on age and weight,
      influenced test reliability. Although the confidence interval width for ejection
      fraction was narrow (5 U), those for peak early (E) and late (A) diastolic
      velocities were wide, resulting in a confidence interval width for the E/A ratio
      of 1.5. CONCLUSIONS: The temporal variability, particularly in obese or elderly
      patients, or both, of echocardiography for measurement of left ventricular mass
      precludes its use to measure changes in mass of the magnitude likely to occur
      with therapy. Measurement stability is affected by study quality, and age and
      body weight both influence study quality. Although ejection fraction shows little
      temporal variability, the large width of the confidence interval of the Doppler
      E/A ratio impairs its use to serially measure diastolic function.

PMID- 7829798
TI  - Comparison of initial detection and redetection of ventricular fibrillation in a
      transvenous defibrillator system with automatic gain control.
AB  - OBJECTIVES: The purpose of this study was to prospectively evaluate postshock
      redetection of ventricular fibrillation by a system that coupled an implantable
      cardioverter-defibrillator with an automatic gain control sense amplifier and a
      transvenous lead system. BACKGROUND: Redetection of ventricular fibrillation
      after an unsuccessful first shock has not been systematically evaluated. Previous
      studies have suggested that sensing performance of some lead systems may be
      adversely affected by the delivery of subthreshold shocks. METHODS: The time
      required for both initial detection and redetection of ventricular fibrillation
      was compared in 22 patients. These times were estimated by subtracting the
      capacitor charge time from the total event time. RESULTS: A total of 113
      successful and 57 unsuccessful initial shocks were delivered during induced
      ventricular fibrillation. The mean +/- SD initial time to detection of
      ventricular fibrillation was 5.5 +/- 1.7 s (range 2.4 to 10.8); the time to
      redetection ranged from 1.5 to 18.5 s (mean 4.5 +/- 2.8, p = NS vs. detection
      time). Abnormal redetection episodes, defined as a redetection time > 10.2 s
      (i.e., > 2 SD above the mean redetection time), were observed in 4 (18%) of 22
      patients. CONCLUSIONS: Redetection of ventricular fibrillation after a
      subthreshold first shock may be delayed. Device testing with intentional delivery
      of subthreshold shocks to verify successful postshock redetection of ventricular
      fibrillation should be performed routinely in all patients.

PMID- 7829799
TI  - Localization and radiofrequency catheter ablation of left-sided accessory
      pathways during atrial fibrillation. Feasibility and electrogram criteria for
      identification of appropriate target sites.
AB  - OBJECTIVES: The purpose of the present study was to assess the feasibility of and
      electrophysiologic criteria for successful radiofrequency catheter ablation of
      left-sided accessory pathways during atrial fibrillation in patients with Wolff
      Parkinson-White syndrome. BACKGROUND: The onset of recurrent or sustained atrial
      fibrillation can complicate or significantly prolong accessory pathway catheter
      ablation procedures. METHODS: We studied 19 consecutive patients (mean age [+/
      SD] 44 +/- 16 years) with Wolff-Parkinson-White syndrome who had ongoing atrial
      fibrillation with rapid anterograde conduction over the accessory pathway (mean
      ventricular rate [+/-SD] 173 +/- 26 beats/min, range 130 to 220) at the beginning
      of the localization procedure during radiofrequency catheter ablation.
      Localization and ablation of the accessory pathway were performed with a 7F
      deflectable catheter (4-mm tip) that was placed underneath the mitral valve
      annulus. The electrophysiologic criteria from unipolar and bipolar local
      electrograms were compared for successful (n = 18) and unsuccessful (n = 39)
      sites. RESULTS: The accessory pathways were localized in the left posteroseptal
      (n = 6), posterior (n = 1), posterolateral (n = 7) and lateral (n = 5) regions
      and successfully ablated during atrial fibrillation in 18 (95%) of 19 patients
      with a mean of 3 +/- 2 radiofrequency pulses (range 1 to 8, median 2). Presence
      of an accessory pathway potential (94% vs. 44%), early activation time of the
      ventricular electrogram (-3.2 +/- 9.2 vs. -15.3 +/- 12.6 ms) and recording of
      atrial activation (88% vs. 61%) from the ablation catheter were helpful in
      identifying successful sites (p < 0.001, p < 0.001 and p < 0.05, respectively,
      compared with unsuccessful sites). In addition, the ventricular activation time
      in relation to the intrinsic deflection of the unipolar electrogram was
      significantly earlier at successful than unsuccessful sites (18.1 +/- 4.8 vs.
      24.4 +/- 6.6 ms, p < 0.01). A QS complex on the unipolar electrogram was observed
      at 96% of successful sites and at 94% of unsuccessful sites (p = 0.74).
      Multivariate logistic regression analysis revealed that the presence of an
      accessory pathway potential (p < 0.002) and early ventricular activation time in
      relation to the onset of the QRS complex (p < 0.001) were independent predictors
      of ablation success. CONCLUSIONS: Localization and radiofrequency catheter
      ablation of left-sided accessory pathways is possible in patients with sustained
      atrial fibrillation and rapid anterograde conduction over the accessory pathway
      during the ablation procedure. The electrophysiologic criteria described here can
      be used to reliably identify successful sites for radiofrequency ablation.

PMID- 7829800
TI  - Left atrial appendage thrombus is not uncommon in patients with acute atrial
      fibrillation and a recent embolic event: a transesophageal echocardiographic
      study.
AB  - OBJECTIVES: The objective of this study was to determine the frequency of left
      atrial thrombus in patients with acute atrial fibrillation. BACKGROUND: It is
      commonly assumed but unproved that left atrial thrombus in patients with atrial
      fibrillation begins to form after the onset of atrial fibrillation and that it
      requires > or = 3 days to form. Thus, patients with acute atrial fibrillation
      (i.e., < 3 days) frequently undergo cardioversion without anticoagulation
      prophylaxis. METHODS: Three hundred seventeen patients (250 men, 67 women; mean
      [+/- SD] age 64 +/- 12 years) with acute (n = 143) or chronic (n = 174) atrial
      fibrillation were studied by two-dimensional transesophageal echocardiography.
      RESULTS: Left atrial appendage thrombus was present in 20 patients (14%) with
      acute and 47 patients (27%, p < 0.01) with chronic atrial fibrillation. In
      patients with a recent embolic event, the frequency of left atrial appendage
      thrombus did not differ between those with acute (5 [21%] of 24) and those with
      chronic (12 [23%] of 52, p = NS) atrial fibrillation. Patients with acute versus
      chronic atrial fibrillation, respectively, did not differ (p = NS) in mean age
      (64 +/- 13 vs. 65 +/- 11 years), frequency of concentric left ventricular
      hypertrophy (32% vs. 26%), hypertension (32% vs. 41%), coronary artery disease
      (35% vs. 39%), congestive heart failure (43% vs. 48%), mitral stenosis (4% vs.
      7%) or mitral valve replacement (1.4% vs. 6%). The minimally detectable
      difference in proportions between patients with acute and chronic atrial
      fibrillation based on a power of 0.80 and base proportion of 0.20 was 14%.
      CONCLUSIONS: Left atrial thrombus does occur in patients with acute atrial
      fibrillation < 3 days in duration. The frequency of left atrial thrombus in
      patients with recent emboli is comparable between those with acute and chronic
      atrial fibrillation. These data suggest that patients with acute atrial
      fibrillation for < 3 days require anticoagulation prophylaxis or evaluation by
      transesophageal echocardiography before cardioversion and should not be assumed
      to be free of left atrial thrombus.

PMID- 7829801
TI  - Determinants of successful balloon valvotomy in infants with critical pulmonary
      stenosis or membranous pulmonary atresia with intact ventricular septum.
AB  - OBJECTIVES: This study reviewed our experience with percutaneous balloon
      valvotomy in infants with critical pulmonary stenosis or membranous pulmonary
      atresia with intact ventricular septum and defined the anatomic and hemodynamic
      characteristics of infants in whom this procedure is successful and provides
      definitive therapy. BACKGROUND: Unlike children with valvular pulmonary stenosis,
      the follow-up of infants with critical pulmonary stenosis undergoing percutaneous
      balloon valvotomy is limited. METHODS: Between December 1987 and August 1992,
      percutaneous balloon valvotomy was attempted in 12 infants with critical
      pulmonary stenosis (n = 10) or pulmonary atresia with intact ventricular septum
      (n = 2). Two outcome groups were identified: Group A patients are acyanotic, have
      mild residual pulmonary stenosis and have not required operation; Group B
      patients have required operation. RESULTS: Of the 12 infants, 11 had a successful
      balloon valvotomy procedure. Group A patients (n = 7) have a residual gradient of
      22 +/- 18.7 mm Hg (mean +/- SD) at follow-up of 3.2 years (range 1.2 to 5.0). In
      Group B (n = 5), operation was required for inability to cross the pulmonary
      valve (n = 1) or persistent severe hypoxemia for > or = 2 weeks after valvotomy
      (n = 4). Significant differences (p < or = 0.01) between the two groups (Group A
      vs. Group B) were identified in pulmonary valve annulus (Z value) 8.1 mm (-1.1)
      versus 5.5 mm (-3.4); tricuspid valve annulus (Z value) 14.0 mm (0.8) versus 8.8
      mm (-1.8); right ventricular volume 65 versus 29 ml/m2; and Lewis index 10.9
      versus 8.9. CONCLUSIONS: Percutaneous balloon valvotomy is effective and likely
      to provide definitive therapy in infants with critical pulmonary stenosis or
      membranous pulmonary atresia with intact ventricular septum who have a tricuspid
      valve annulus > 11 mm, pulmonary valve annulus > or = 7 mm and right ventricular
      volume > 30 ml/m2.

PMID- 7829802
TI  - Primary pulmonary hypertension in children: clinical characterization and
      survival.
AB  - OBJECTIVES: This study characterized mortality in a group of Mexican children (n
      = 18, mean [+/- SD] age 9.9 +/- 3 years) with primary pulmonary hypertension and
      investigated the factors associated with their survival. BACKGROUND: Primary
      pulmonary hypertension is a progressive, fatal disease of unknown cause.
      Establishing the diagnosis earlier in life may influence prognosis. METHODS: A
      dynamic cohort of children with primary pulmonary hypertension were enrolled
      between December 1977 and May 1991 and followed up through September 1992.
      Measurements included hemodynamic and pulmonary function variables in addition to
      demographic data, medical history and response to vasodilator treatment. We also
      compared the survival estimates of these children with those of our adult
      patients with primary pulmonary hypertension (n = 42, mean age 27.9 +/- 8.5
      years). RESULTS: Baseline mean (+/- SD) pulmonary artery pressure was similar in
      children and adults (66 +/- 15 vs. 65 +/- 18 mm Hg, p = NS), but a higher cardiac
      index resulted in a lower mean pulmonary vascular resistance index in children
      (18 +/- 7 vs. 26 +/- 12 U/m2, p < 0.01). The proportion of patients who had a
      positive hemodynamic response to vasodilator treatment was higher in children
      than in adults (41% vs. 25%). Estimated median survival in children was 4.12
      years (95% confidence interval [CI] 0.75 to 8.66) and 3.12 years in adults (95%
      CI 0.5 to 13.25, chi-square log-rank 0.81, p = NS). Elevated right atrial
      pressure (rate ratio 10.2) and decreased stroke volume index (rate ratio 32.9)
      were the only significant predictors of mortality (Cox proportional hazards
      model). CONCLUSIONS: Children with primary pulmonary hypertension have a poor
      survival expectancy, which does not appear to differ from that in adults with
      primary pulmonary hypertension. Mortality in childhood primary pulmonary
      hypertension is also associated with variables that assess right ventricular
      dysfunction.

PMID- 7829803
TI  - Fibrous obstruction within the left ventricular outflow tract associated with
      ventricular septal defect: a pathologic study.
AB  - OBJECTIVES: We examined the nature of ridges within the left ventricular outflow
      tract associated with ventricular septal defects that might be found by
      echocardiography. BACKGROUND: Echocardiography displays even small ridges well.
      Surgical removal of such ridges at the time of defect closure is recommended.
      METHODS: We examined 37 heart specimens with ventricular septal defects with a
      ridge, noting its nature and relation to the defect and adjacent valves. We
      excluded left ventricular outflow tract obstruction associated with complex
      lesions. RESULTS: Defects were perimembranous in 25 specimens, muscular in 8 and
      part of an atrioventricular septal defect in 5. Some hearts had multiple defects.
      Many of the original reports had not mentioned ridges. Three distinct ridge
      patterns were found. The first (n = 18) was a fold of endocardial tissue related
      to the membranous septum. The second (n = 12) was a defect of a fibrous nature;
      in 8 this was a discrete, protuberant fibrous ridge, and in 4 the obstruction was
      diffuse, which we termed keloidal. The third pattern (n = 7) lay
      circumferentially around the ventricular septal defect, seemingly associated with
      the defect's attempted spontaneous diminution in size. Endocardial folds were not
      found in specimens from patients > 5 years old. Fibrous and keloidal lesions,
      which may represent a continuum of progression, generally were found in specimens
      from older patients. Histologic studies of 17 specimens confirmed the morphologic
      findings. The endocardial folds were endothelial tissue, whereas the fibrous and
      keloidal ridges were of fibrous tissue, as were circumferential lesions. All
      specimens had mitral-semilunar valvular continuity. CONCLUSIONS: Endocardial fold
      and circumferential lesions appear to be benign. The endocardial folds arose from
      the membranous ventricular septum, were not protuberant and usually were found in
      younger patients. The fibrous ridges, in contrast, were protuberant and were
      always associated with the underlying muscle of the outlet septum. These
      pathologic distinctions may facilitate echocardiographic diagnosis and prognosis.

PMID- 7829804
TI  - Delineation of site, relative size and dynamic geometry of atrial septal defects
      by real-time three-dimensional echocardiography.
AB  - OBJECTIVES: This study attempted to determine the site, relative size and dynamic
      geometry of atrial septal defects using dynamic three-dimensional
      echocardiography. BACKGROUND: Recent studies have demonstrated the feasibility of
      dynamic three-dimensional echocardiography. Images are acquired from computerized
      reconstruction of sequential, tomographic ultrasound "slices" of the heart.
      Ultrasound images can be obtained by linear progression of a transducer within a
      transesophageal imaging probe. In small infants and children the large transducer
      size has not allowed transesophageal placement, and the probe has been placed on
      the thorax or in the subcostal position. Other scanning devices, housed in
      plastic containers, acquire images in a rotational format and can also be placed
      in a transthoracic or subcostal position. METHODS: Specially designed
      transesophageal probes and a dedicated computer unit were used for two
      dimensional image retrieval and reconstruction of three-dimensional images.
      Sixteen patients with atrial septal defects were studied (median age 18 months,
      range 1 day to 18 years). In one patient, images were obtained by transesophageal
      probe placement; in the other 15 patients, the probe was placed in the
      transthoracic or subcostal position. RESULTS: A dynamic three-dimensional
      echocardiogram of the atrial septal defect could be obtained in 13 of the 16
      patients. The distinguishing features of the atrial septal defects and their
      spatial orientation could be visualized in unique three-dimensional views.
      CONCLUSIONS: Dynamic three-dimensional imaging could be applied to the specific
      evaluation of atrial septal defects. Unique views of the heart allowed for
      spatial comprehension of the defects, rendering potentially important clinical
      information.

PMID- 7829805
TI  - Presentation and attrition in complex pulmonary atresia.
AB  - OBJECTIVES: This study summarized patterns of presentation and attrition in
      complex pulmonary atresia. BACKGROUND: Assessment of the potential impact of
      surgical strategies for managing complex pulmonary atresia requires information
      about variability in age and physiology at presentation of the condition.
      METHODS: We performed a retrospective review of age at presentation, referral
      source, pulmonary artery and collateral anatomy and surgical history of 218
      patients from two institutions dealing with congenital heart disease throughout
      life. RESULTS: Approximately 65% of pulmonary atresia appears in infancy, with
      50% of patients severely symptomatic from cyanosis and 25% from heart failure.
      Compared with those presenting undiagnosed, patients referred secondarily for
      specialist management tend to be older when first seen, and care must be taken
      when generalizing about the natural history of the condition from their survival
      experience. Overall actuarial survival, including the effects of operation,
      suggests that 60% (95% confidence limits [CL] 43 to 73) of patients presenting in
      infancy survive to their first birthday, 65% (95% CL 51 to 74) of those alive at
      1 year old survive to the age of 10, and 16% (95% CL 5 to 31) of those alive at
      10 years old survive to age 35. CONCLUSIONS: Novel surgical approaches have
      generally been applied beyond infancy in patients selected by their survival
      through the period of greatest attrition for this disease. Unless successful
      application in symptomatic infants is demonstrated, we cannot assume that these
      serial and complicated operations will have a major impact on the outlook of most
      patients with complex pulmonary atresia.

PMID- 7829806
TI  - Clinical evaluation of left heart Doppler contrast enhancement by a saccharide
      based transpulmonary contrast agent. The Levovist Cardiac Working Group.
AB  - OBJECTIVES: A multicenter study was carried out to evaluate the efficacy with
      which SHU 508A enhances left heart Doppler signals and improves the clinical
      quantification of valve disease. BACKGROUND: Poor signal-to-noise ratio often
      limits the Doppler interrogation of left heart flows. This problem may be
      resolved by the enhancement of Doppler signals by an ultrasound contrast agent
      capable of pulmonary transmission, such as the recently developed SHU 508A.
      METHODS: Left heart contrast enhancement was tested for 1) continuous wave
      Doppler evaluation in 51 patients with aortic stenosis, 2) pulsed Doppler
      transthoracic evaluation of pulmonary venous flow in 85 patients, and 3) color
      Doppler evaluation of mitral regurgitation in 60 patients. Studies were performed
      immediately before and during the intravenous administration of SHU 508A (16 ml
      of 200 mg/ml) and compared with unenhanced transesophageal data in representative
      subsets of patients. RESULTS: SHU 508A had no serious adverse effects. A
      significant increase in left heart Doppler signal intensity lasted for 30 to 300
      s. The continuous wave Doppler velocity envelope was enhanced for all jets, but
      Doppler peak velocity was not altered in high quality baseline studies. However,
      Doppler contrast enhancement resulted in higher measured peak gradients (p <
      0.001) in 29 patients with aortic stenosis who had poor quality baseline studies.
      This improved the overall correlation with invasive pressure measurements (r =
      0.73 vs. r = 0.89, p < 0.01). The enhanced pulsed Doppler traces of transthoracic
      pulmonary venous flow allowed quantitative analysis in 92% patients (vs. 27% at
      baseline) and correlated well with peak velocities and velocity profiles obtained
      by transesophageal echocardiography (r = 0.91, p < 0.001). The enhanced color
      Doppler display of regurgitant jets increased jet area with a high
      interindividual variability (mean 276%), resulting in almost identical jet areas
      as unenhanced transesophageal values (r = 0.97, p < 0.001). CONCLUSIONS: SHU 508A
      is a safe transpulmonary contrast agent that significantly enhances both spectral
      and color Doppler signals in the left heart. In specific patient subsets, the
      increase in signal-to-noise ratio improved the quantitative assessment of aortic
      stenosis, pulmonary venous flow and mitral regurgitation.

PMID- 7829807
TI  - Visually discernible myocardial echocardiographic contrast after intravenous
      injection of sonicated dextrose albumin microbubbles containing high molecular
      weight, less soluble gases.
AB  - OBJECTIVES: The central hypothesis of this study was that microbubble survival,
      and subsequent left ventricular and myocardial ultrasound contrast, could be
      improved by altering microbubble gas to consist of a higher molecular weight
      (less diffusible) and less soluble gas. BACKGROUND: Microbubble survival after
      intravenous injection is shortened because of rapid diffusion of blood-soluble
      room air gases (nitrogen and oxygen) across the permeable bubble membrane into
      blood. METHODS: Thirteen open chest dogs received intravenous injections of a
      constant dose of sonicated dextrose albumin that was incubated with either room
      air or 100% nitrogen, 100% helium or 100% sulfur hexafluoride. Nitrogen (100%) is
      less blood soluble than room air, whereas helium and sulfur hexafluoride are the
      least soluble. Sulfur hexafluoride has the slowest diffusion rate. To further
      decrease the diffusion rate, each sample was administered during inhalation of
      room air and again during brief inhalation of the same gas with which it had been
      incubated. RESULTS: The highest peak videointensity in the left ventricular
      cavity was produced by the sonicated dextrose albumin incubated with sulfur
      hexafluoride, the gas having lowest blood solubility and diffusion rate, while
      sulfur hexafluoride was briefly inhaled during the period of intravenous
      injection (peak videointensity 139 +/- 10 vs. 54 +/- 11 for room air-exposed
      sonicated dextrose albumin, p < 0.001). Myocardial contrast was visually evident
      in > 80% of the intravenous injections of sulfur hexafluoride-exposed sonicated
      dextrose albumin when the agent was given as an 8-fold concentrated sample during
      brief inhalation of sulfur hexafluoride. CONCLUSIONS: Visual myocardial
      echocardiographic contrast is possible after intravenous injection of sonicated
      dextrose albumin if the microbubbles contain a gas with low blood solubility and
      diffusivity.

PMID- 7829808
TI  - Restenosis after percutaneous transluminal coronary angioplasty: have we been
      aiming at the wrong target?
AB  - Restenosis after percutaneous coronary balloon angioplasty remains a significant
      problem. Despite success with a variety of agents in animal models, no agent has
      proved clearly successful in reducing restenosis in humans. There are many
      potential reasons for this, but one possibility is that because of our incomplete
      understanding of the restenotic process, therapy has been directed at the wrong
      target. Arterial remodeling (changes in total vessel area or changes in area
      circumscribed by the internal elastic lamina) is well described in de novo
      atherosclerosis, and there is increasing evidence that this process occurs after
      angioplasty. Thus, restenosis can be thought of not merely as neointimal
      formation in response to balloon injury, but as arterial remodeling in response
      to balloon injury and neointimal formation. Arterial remodeling may consist of
      actual constriction of the artery, as has been described in some animal models
      and in preliminary fashion in humans, or of compensatory enlargement as has been
      described in de novo atherosclerosis and in the hypercholesterolemic rabbit iliac
      artery model. Arterial constriction can result in restenosis with minimal
      neointimal formation. Compensatory enlargement accommodates significant amounts
      of neointimal formation, with preservation of lumen area despite an increase in
      neointimal area adequate to cause restenosis in a noncompensated artery. This
      expanded paradigm of arterial remodeling and intimal formation may in part
      account for the lack of success in clinical trials to date, and therapy directed
      at arterial remodeling as well as intimal formation may be required to reduce
      restenosis after coronary interventions.

PMID- 7829809
TI  - Guidelines for clinical use of cardiac radionuclide imaging. Report of the
      American College of Cardiology/American Heart Association Task Force on
      Assessment of Diagnostic and Therapeutic Cardiovascular Procedures (Committee on
      Radionuclide Imaging), developed in collaboration with the American Society of
      Nuclear Cardiology.

PMID- 7829810
TI  - What concerns us about managed care?

PMID- 7829811
TI  - Relation between QT and RR intervals.

PMID- 7829812
TI  - Correcting the QT interval: is it relevant?

PMID- 7829813
TI  - Atrial function can only be assessed by combined use of volume- and pressure
      assessing noninvasive methods.

PMID- 7829814
TI  - Heparin and aspirin in unstable angina: insufficient sample size may lead to
      erroneous conclusions.

PMID- 7829815
TI  - Early repair of tetralogy of Fallot and ventricular arrhythmia.

PMID- 7829816
TI  - Cardiovascular disease in women.

PMID- 7829817
TI  - Coronary heart disease in women: gender differences in diagnostic evaluation.
AB  - Although women who sustain coronary events (myocardial infarction, coronary
      bypass graft surgery, or percutaneous transluminal coronary angioplasty) have
      less favorable outcomes than do their male counterparts, the optimal approach to
      the evaluation of women with chest pain has not yet been ascertained. There is
      substantial documentation of the lesser use of invasive diagnostic and
      therapeutic interventions for women than for men, despite symptoms of comparable
      or greater severity among women. This report reviews the information available to
      guide the selection of noninvasive test procedures for women with chest pain
      syndromes, highlighting clinical variables, particularly the characteristics of
      the chest pain and the coronary risk profile. Because coronary arteriography
      appears to be a major determinant of access to myocardial revascularization
      procedures, the less aggressive diagnostic evaluation of women with chest pain in
      general, and of those with abnormal noninvasive test results in particular,
      remains of concern. The role of gender differences in diagnostic testing in
      determining the worse prognosis of clinically manifest coronary disease in women
      has yet to be delineated.

PMID- 7829818
TI  - Coronary heart disease in women: risk factors and prevention.
AB  - Coronary heart disease in women can be prevented or reduced by identifying risk
      factors and modifying behavior. The optimal recommendations, which may differ
      from those for men, are based on the appropriate consideration of women's risk
      factors. The strongest risk factors for women are increasing age, diabetes,
      tobacco use, and high-density lipoprotein level. This paper reviews the risk
      factors for coronary heart disease as they apply to women, emphasizing the gender
      differences in risk factor impact and modification on mortality and morbidity.

PMID- 7829819
TI  - Mitral valve prolapse.
AB  - Mitral valve prolapse (MVP) is usually a primary, dominantly inherited condition.
      Diagnosis may be made by auscultation of a midsystolic click and late-systolic
      murmur that move dynamically with postural maneuvers. Echocardiography confirms
      the diagnosis by demonstrating M-mode late-systolic prolapse and 2-D leaflet
      billowing into the left atrium. More severe forms of MVP can be detected
      echocardiographically by documentation of significant mitral regurgitation,
      enlargement and thickening of the mitral leaflets and anulus, and loss of leaflet
      apposition. In contrast to earlier reports, the true "MVP syndrome" consists of
      low body weight and blood pressure, minor skeletal abnormalities, orthostatic
      hypotension, palpitations and mitral regurgitation of variable degree.
      Complications of MVP include progressive mitral regurgitation, infective
      endocarditis, and possible risk of neurologic ischemia, arrhythmic sudden death,
      and orthostatic syncope. Risk factors for complications among MVP patients
      include older age, male gender, the presence of a mitral regurgitant murmur, and,
      possibly, higher weight and blood pressure. MVP patients with neither a murmur
      nor Doppler evidence of mitral regurgitation may be reassured that their
      condition is benign. For other MVP patients, the presence and severity of mitral
      regurgitation govern the frequency and intensiveness of needed follow-up.

PMID- 7829820
TI  - Stroke and its effect in women.
AB  - The purpose of this paper is to briefly discuss the demographies, risk factors,
      primary and secondary prevention, and outcome of cerebrovascular disease in
      women. Overall, an equal number of men and women suffer strokes: after age 75,
      however, women stroke victims outnumber men. This is a particular concern because
      the prognosis for recovery of functional independence is less favorable at older
      ages. Risk factor management and secondary prevention efforts can reduce the
      impact of stroke on its victims and on society. Controlled clinical trials
      addressing the role of hormone replacement therapy in the prevention of stroke in
      older women are needed.

PMID- 7829821
TI  - Managing heart disease: a study of the experiences of older women.

PMID- 7829822
TI  - Type 1 diabetes before clinical diagonsis.

PMID- 7829823
TI  - The genes influencing the susceptibility to IDDM in humans.

PMID- 7829824
TI  - Autoantigens in type 1 diabetes mellitus.

PMID- 7829825
TI  - GAD, diabetes, and Stiff-Man syndrome: some progress and more questions.

PMID- 7829826
TI  - Autoantibodies in insulin-dependent diabetes mellitus.

PMID- 7829827
TI  - Prediction and prevention of type I diabetes.

PMID- 7829828
TI  - Defective major histocompatibility complex class I expression on lymphoid cells
      in autoimmunity.

PMID- 7829829
TI  - Prevention of xenograft rejection by masking donor HLA class I antigens.

PMID- 7829830
TI  - T-cell reactivity to 38 kD insulin-secretory granule protein in patients with
      recent onset type 1 diabetes.

PMID- 7829831
TI  - A bovine albumin peptide as a possible trigger of insulin-dependent diabetes
      mellitus.

PMID- 7829832
TI  - Suppression of diabetes in nonobese diabetic mice by oral administration of
      porcine insulin.

PMID- 7829833
TI  - Inverse relation between humoral and cellular immunity to glutamic acid
      decarboxylase in subjects at risk of insulin-dependent diabetes.

PMID- 7829834
TI  - Spontaneous loss of T-cell tolerance to glutamic acid decarboxylase in murine
      insulin-dependent diabetes.

PMID- 7829835
TI  - Immune response to glutamic acid decarboxylase correlates with insulitis in non
      obese diabetic mice.

PMID- 7829836
TI  - Prevention of autoimmune diabetes in the BB rat by intrathymic islet
      transplantation at birth.

PMID- 7829837
TI  - Genetic variation in the triploids of Japanese Fasciola species, and
      relationships with other species in the genus.
AB  - Twelve enzymes (encoded by 14 loci) in liver flukes of Fasciola species
      originating from Japan (parthenogenetic triploids), Korea (parthenogenetic
      diploids), the United States of America (USA) and Australia (all sexual diploids)
      were analysed using starch gel electrophoresis. Variation in electrophoretic
      patterns between samples was detected at fic enzyme loci (Ak, Got, Gpi, 6-Pgd and
      Pgm-2). Japanese worms (31, of which six were established as uniparental
      laboratory strains), which reproduce by parthenogenesis, exhibited three
      different isozyme patterns. This indicates that triploidy has arisen more than
      once in Japanese flukes. Japanese Fasciola sp. can be separated into three types
      on morphological grounds. For the six laboratory strains of Japanese worms, the
      parental morphological type was known. Each of the three isozyme patterns
      observed was restricted to one morphological type. Most alleles detected in the
      Japanese triploids were also found in diploid worms from the other countries: the
      only alleles not represented elsewhere were four at the Got locus and two at the
      Pgm locus. Flukes from a laboratory strain derived from a single Korean diploid
      worm resembled the Japanese worms in genotype more closely than did America
      (seven uniparental laboratory strains) or Australian (30 worms) specimens. Worms
      from the last two countries were closely related.

PMID- 7829838
TI  - Effect of ivermectin on infection with gastro-intestinal nematodes in Sierra
      Leone.
AB  - Levels of intestinal nematode infections were assessed six months after a two
      year trial of ivermectin for efficacy against onchocerciasis had ended. In the
      trial the inhabitants of six villages in Sierra Leone were offered treatment with
      ivermectin or placebo at six monthly intervals for four rounds in total.
      Quantitative faecal egg counts were carried out on stool samples provided by 202
      subjects, all of whom had received all four rounds of treatment, in two of the
      villages (Dodo and Mogibisi). These data were analysed by a novel procedure in
      which a 3-way ANOVA with negative binomial errors enabled village and host gender
      influences on the outcome of treatment to be identified. Necator americanus was
      the most common species showing an overall prevalence of 90% but a higher
      intensity in Mogibisi relative to Dodo, particularly among male subjects. Neither
      prevalence nor intensity of infection were altered in ivermectin-treated compared
      with placebo-treated subjects. Trichuris trichiura was the least common species
      with a prevalence of 15%. It was concluded that there was no significant
      protection from infection with this species among the ivermectin relative to the
      placebo-treated subjects. Ascaris lumbricoides, with an overall prevalence of
      39%, was more common among female (50%) compared with male (27%) villagers.
      Prevalence was not significantly affected by ivermectin but the intensity of
      infection declined by 91.3% in Dodo whilst in Mogibisi intensity was only reduced
      by 14.6%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7829839
TI  - Relationship between the excretion of protostrongylid larvae in sheep in north
      west Spain and climatic conditions.
AB  - The relationship between different climatic factors (temperature, relative
      humidity and rainfall) and the pattern of lungworm larval excretion was studied
      in sheep under a continuous grazing pattern in North-west Spain, where the
      climate is intermediate between sub-humid Mediterranean with an Atlantic tendency
      and European Atlantic. Over a period of one year, 44 animals were sampled once a
      month at random from a flock of 80 Galician breed sheep, all over 4 years old.
      Faeces were taken directly from the rectum and the number of first stage larvae
      per gram of faeces was determined for each animal, and the species of
      Protostrongylidae (Nematoda) identified. Larval excretion was irregular during
      the study. The prevalence and intensity of infection were greater in the colder
      months (40.9%; x = 12.3 +/- 40.4) and less in the warmer months (21.9%; mean =
      0.7 +/- 2.7). The species of Protostrongylidae identified and prevalences (%)
      were Neostrongylus linearis (71.5), Muellerius capillaris (18.8) and Cystocaulus
      ocreatus (9.7). Between November and March, with low temperatures, the prevalence
      and intensity of parasitism with N. linearis and M. capillaris were greater than
      in the months with high temperatures (May to September). Multiple linear
      regression analysis showed statistical correlation between temperature, relative
      humidity and rainfall considered together and the number of N. linearis larvae
      per gram of faeces. Linear regression showed a correlation between the
      temperature and the percentage of sheep that passed M. capillaris. In general,
      the prevalence and intensity of infection of the sheep with N. linearis, M.
      capillaris and C. ocreatus larvae decrease when the temperature increases and
      increase when the relative humidity and rainfall increases.

PMID- 7829840
TI  - Infectivity, growth, distribution and fecundity of a six versus twenty-five
      metacercarial cyst inoculum of Echinostoma caproni in ICR mice.
AB  - Female ICR mice, 6-8 weeks old, were exposed to 6 (group A) or 25 (group B)
      metacercarial cysts/host of Echinostoma caproni to determine the effects of these
      cyst dosages on infectivity, growth, distribution and fecundity of worms in the
      small intestines. All 30 mice exposed (15 in group A and 15 in group B) were
      infected and there was no significant difference in the percentage of worm
      recovery between group A and B at 2, 4 and 8 weeks postinfection (PI). Growth was
      rapid in both groups with worm body areas increasing from about 3mm2 at 2 weeks
      PI to about 7 mm2 at 8 weeks PI. More worms from group B were in the anterior
      sections of the small intestines at 2 and 4 weeks PI than those from group A.
      However, at 8 weeks PI more worms from Group A were in the anterior sections of
      the small intestines than those from group B. There were marked differences in
      our findings on infectivity, growth and distribution of E. caproni in ICR mice
      using 6 and 25 cyst inocula compared to a previous study using the same
      echinostome and cyst inocula in NMRI mice, presumably related to the mouse
      strain. Fecundity studies were somewhat comparable in both studies showing an
      approximate three to four times increase in the average number of eggs/gram of
      faeces in mice receiving 25 versus 6 cyst inocula.

PMID- 7829841
TI  - Larval development of ovine Neostrongylus linearis in four experimentally
      infected mollusc species.
AB  - Development of Neostrongylus linearis larvae was studied in the snail
      intermediate hosts Oestophora (Oestophora) barbula, Oestophorella buvinieri,
      Cepaea nemoralis and Helix (Cryptomphalus) aspersa. The molluscs of each species,
      all adults, were divided into groups of 40 for infection purposes. The infection
      doses for the first two snail species were 90 and 50 first stage larvae (L1) of
      N. linearis, respectively. For C. nemoralis two batches were tested: one with 200
      L1 kept at 19 degrees C and the other with 250 L1 at a temperature of 21 degrees
      C. The same was done with Helix (C.) aspersa with 200 L1 at a temperature of 21
      degrees C, on the one hand and 300 L1 at 24 degrees C on the other. One or two
      molluscs of each species were killed in series from the 6th day post-infection
      (p.i.) until the 44th. Percentage values for total larvae (1, 2 and 3) and L3
      were higher with the lower dose for C. nemoralis, whilst the same was true with
      the higher dose in Helix (C.) aspersa. In both cases, the higher temperature
      appeared to contribute to cycle acceleration. Using one way analysis of variance,
      statistically significant differences were detected between the species of
      molluscs tested concerning percentages of L1 which penetrated, total larvae and
      L3. According to our results, the decreasing order of susceptibility of these
      species of molluscs as experimental intermediate hosts of N. linearis is: O.
      buvinieri, Oestophora (O.) barbula, C. nemoralis and Helix (C.) aspersa. It is
      the first time that Oestophora (O.) barbula and Oestophorella buvinieri have been
      named as experimental intermediate hosts of N. linearis.

PMID- 7829842
TI  - Ultrastructure and histochemistry of the tegument of juvenile paramphistomes
      during migration in Indian ruminants.
AB  - The tegument of juvenile Paramphistomum epiclitum and Fischoederius elongatus
      (Paramphistomidae: Digenea) resembles those of other digeneans. Seven types of
      papillae were observed, mostly on the oral and acetabular surfaces, and increase
      in number during migration. Also evident are two types of secretory body (T1 and
      T2) which are synthesized separately in tegumental cytons underlying the
      syncytium. Exocytosis of T2 bodies occurs at the apical membrane and appears to
      contribute to a fibrous glycocalyx. The tegumental syncytium lining the pharynx
      and acetabulum is thinner and has a higher capacity for vacuolation than the
      general tegument. These may represent important sites for osmoregulation. The
      absence of mitochondria from the tegument in migrating juveniles suggests limited
      involvement in energy demanding processes. Pigmentation of the subtegument is
      first evident in mature cercariae and is progressively eliminated during
      migration.

PMID- 7829843
TI  - Stage-specific development of a filarial nematode (Dipetalonema dracunculoides)
      in vector ticks.
AB  - This paper reports the development of the canid filarial worm, Dipetalonema
      dracunculoides, in the brown dog tick, Rhipicephalus sanguineus by determining
      whether development is similar within larval, nymphal and adult stages of
      infected ticks. This study demonstrates that only infected nymphal ticks can
      support the complete development of the filarial worm. Infected larval ticks are
      not suitable intermediate hosts, nor are infected adults. Development depends on
      some stage-specific property of the vector, and the maturation to the infective
      stage is stimulated during the course of the nymphal-adult moult.

PMID- 7829844
TI  - Prevalence of Toxocara canis ova in public playgrounds in the Dublin area of
      Ireland.
AB  - A total of nine playground sites in Dublin city and county were surveyed from
      which 228 samples were removed. Of these samples, 15% were positive for Toxocara
      canis ova and a mean egg density of 1.4 ova/100 g was calculated. Two types of
      playground sites were identified and that the level of toxocaral contamination
      was found to be greater in 'neighbourhood playgrounds' than in 'adventure
      playgrounds'. There was no significant difference in the number of positive
      samples taken from sites both inside and outside these playgrounds. No evidence
      of Toxocara cati ova was found. Only one sample was positive for Toxascaris
      leonina ova. Over 50% of the T. canis ova identified were infective. The findings
      in this study suggest that the sample's moisture content contributes to the long
      term survival of infective Toxocara ova in the environment. A recovery rate of
      69.8% was achieved with a modified version of the flotation method.

PMID- 7829845
TI  - Prevalence of microfilaraemia in episodic weakness and clinically normal dogs
      belonging to hunting breeds.
AB  - Blood samples from 50 dogs with episodic weakness and 50 clinically normal dogs,
      all belonging to hunting breeds, were examined for microfilariae using the
      modified Knott's method. The prevalence of microfilaraemia in dogs belonging to
      the episodic weakness group was 10% for Dirofilaria immitis, 30% for Dirofilaria
      repens and 8% for Acanthocheilonema reconditum. In the clinically normal group,
      the figures were 14% for Dirofilaria repens and 4% for Acanthocheilonema
      reconditum. The overall percentage of dogs with microfilaremia in the episodic
      weakness group was 44 and that of the clinically normal group 16, with a
      statistically significant difference (P < 0.01). The prevalence of microfilaremia
      due to the nonpathogenic filarial species (Dirofilaria repens, Acanthocheilonema
      reconditum) was 34% and 16% for the episodic weakness group and the clinically
      normal dogs, respectively, with no significant difference.

PMID- 7829846
TI  - The morphology of hymenolepidid and dilepidid cestodes from common and pygmy
      shrews (Soricidae) in southeast England.
AB  - One hundred and six of 109 common shrews (Sorex araneus) and 62 of 72 pygmy
      shrews (S. minutus), obtained by Longworth trapping in Southeast England, were
      infected with cestodes. Ten species were recovered: Choanotaenia hepatica and
      Hymenolepis prolifer (found in S. araneus); Choanotaenia crassiscolex,
      Hymenolepis furcata, H. jacutensis, H. schaldybini, H. scutigera, H. singularis,
      H. diaphana and H. infirma (in both hosts). The morphology, taxonomy and ecology
      of these species are discussed and the findings of the present study are
      discussed with reference to previous studies of the helminth fauna of British
      shrews. Cysticercoids of C. crassiscolex were found in the snail, Vitrina
      pellucida, and cysticercoids of H. schaldybini in the staphylinid beetle,
      Anthobium unicolor.

PMID- 7829847
TI  - Ultrastructure of the male reproductive system in a rumen amphistome Cotylophoron
      cotylophorum.
AB  - The ultrastructure of various regions of the male reproductive tract and the
      prostate gland of Cotylophoron cotylophorum (Trematoda: Digenea) is described.
      The internal lining of the entire male duct system is syncytial in nature, and
      regional variation is quite evident. The syncytial epithelium of the vas deferens
      and seminal vesicle is very thin, flat and lamellate and the lumen is packed with
      spermatozoa. In the pars musculosa (PM) the syncytium is also flat but lamellae
      are sparsely distributed and anastomosed at places to form loops. The syncytium
      of the PM is invested by several layers of circular and longitudinal muscle. The
      pars prostatica (PP) is lined by an uneven but moderately thick syncytial
      epithelium with nuclei projecting into the lumen. The syncytium bears numerous
      very long lamellae. The ejaculatory duct epithelium is devoid of lamellae. It is
      even and moderately thick throughout. The prostate gland cells are uneven in
      outline and bear long ducts which open into the lumen of the PP. They show an
      ultrastructural organization suggestive of protein secretion.

PMID- 7829848
TI  - Complete structure of the gene encoding an immunodominant antigen of Dirofilaria
      immitis and larva-specific synthesis of primary transcript.
AB  - The complete gene encoding an immunodominant antigen of Dirofilaria immitis was
      isolated from a Charomid 9-36 genomic DNA library. This genomic DNA clone termed
      'Dg2' was characterized by restriction mapping, DNA sequencing of the 5' flanking
      region, the exon/intron boundaries and the polyadenylation addition site. The Dg2
      with 4872 bp in length consisted of five exons interspersed with four introns.
      These exons reveal a single open reading frame followed by a long 3' non-coding
      region of 1383 bp. The open reading frame of 969 bp encodes a polypeptide of 322
      amino acids with a molecular weight of 34,400. The ATG translation initiation
      codon starts 22 nucleotides downstream from the 5' end of the first exon. The
      polyadenylation signal sequence. AATAAA, is located at the 3' end of the last
      exon. The transcription initiation site was determined by primer extension
      technique. S1 nuclease mapping analysis demonstrated that the primary transcript
      derived from Dg2 is synthesized in microfilariae but not in male or female adult
      worms. The result suggests that the stage-specific expression of Dg2 is regulated
      at the level of primary transcript.

PMID- 7829849
TI  - Experimental infection of an isolate of Taenia solium from Hainan in domestic
      animals.
AB  - The present study was designed to determine the susceptibility of domestic
      animals to an isolate of Taenia solium from Hainan Province, People's Republic of
      China. A total of 162 cysticerci were recovered from two pigs and 21 from two
      dogs after experimental inoculation. Cats, goats and a calf were not susceptible
      to T. solium. Cysticerci were recovered mainly from muscles of the pigs and all
      were alive. The remainder were in the liver and only one was alive. In the dog,
      all cysticerci were recovered from the muscles and all were alive.

PMID- 7829850
TI  - In vitro hatching of oncospheres of Taenia taeniaeformis using eggs isolated from
      fresh, frozen, formalin-fixed and ethanol-fixed segments.
AB  - In order to establish a simple means of handling eggs of taeniid cestodes under
      non-biohazardous conditions, gravid segments of Taenia taeniaeformis were fixed
      in ethanol or formalin or were frozen. In vitro hatching of oncospheres was
      carried out by the 0.5% sodium hypochlorite method using eggs isolated from the
      nonviable and viable segments. No oncospheres hatched from formalized eggs,
      whereas almost all oncospheres hatched from all other eggs but the number of
      oncospheres recovered was highly variable. Oncospheres hatched from eggs isolated
      from frozen segments were highly fragile. The highest figures for in vitro
      hatching of oncospheres were recorded when eggs isolated either from segments
      fixed in 70% ethanol or from viable segments were used.

PMID- 7829851
TI  - Cross-cultural healing.

PMID- 7829852
TI  - Folk healing and biomedicine: culture clash or complimentary approach?
AB  - Health care professionals are often faced with clients who are using alternative
      healing techniques along with biomedicine. A comparison of biomedicine in its
      cultural context to folk healing serves to highlight the cultural aspects of both
      systems. The cult of Fidencio, a popular healer in northern Mexico and southern
      United States, is used to illustrate a folk healing system. Biomedicine is
      presented in a historical context to show the American value of scientific
      objectivity. Current interest in alternative healing in the United States
      challenges the absolute primacy of scientific rationalism and opens the door for
      complementary approaches.

PMID- 7829853
TI  - Transcultural nursing ethics: a framework and model for transcultural ethical
      analysis.
AB  - Increased awareness of cultural diversity in contemporary society and nursing
      mandates the need for transcultural nursing ethics. The core of this ethics
      assumes that all discourse and interaction is transcultural because of strengths
      and differences in values and beliefs of individuals and groups within global
      society. Transcultural ethics addresses how people ought to live when
      subjectively sharing a common world. This article presents a framework and model
      with four parts: Transcultural Caring Dynamics, Principles, Transcultural
      Context, and Universal Source. These incorporate the ethics of virtue, principle,
      values, and belief, respectively. Interactive parts of the holistic process
      provide the foundation for assessing and analyzing transactions to facilitate
      understanding and direction toward culturally based ethical decision making.

PMID- 7829854
TI  - Connections: a contextual model for holistic nursing practice.
AB  - Nursing is a holistic practice in which the science and technology of curing is
      cradled by the art of human caring within a healing context. Caring is the human
      capacity to connect with another from a place of compassion and unconditional
      support in the process of growth and actualizing one's potential in the face of
      human challenge. Healing reflects the process of one's search for wholeness in
      the ultimate expression of one's unique being. This wisdom is multidisciplinary
      and interconnecting, integrating the multidimensional aspects of the human
      process engaged in the art and science of healing.

PMID- 7829855
TI  - The lived experience of care within the context of cultural diversity.
AB  - This study explored the health promotion experiences of 10 Euro-American advanced
      practice nurses who provided care in rural settings to predominantly African
      American families. Relational themes that emerged from the discussions of the
      participants were authentic connecting, unconditional help giving, and openness
      to knowing. The constitutive pattern that emerged across all the texts was care
      as uncovering healing. The nurses' knowledge or lack of knowledge about
      differences in cultural health beliefs and practices was in the background,
      whereas the relationship was the contextual core of the experience that
      transcended the knowledge of differences.

PMID- 7829856
TI  - Cultural aspects of caring for Navajo Indian clients.
AB  - Cultural factors significantly influence the Navajo's interactive processes as
      well as perceptions of health and illness. Unfortunately, very limited published
      information is available about the problems that may occur when health care
      practitioners ignore the influence of culture. The interactive processes are made
      even more complex when health care providers have cultural expectations that are
      different from those held by their patients. The article reviews some of the
      complex factors (i.e., family structure, health/illness beliefs, traditional
      remedies, and cultural practitioners) that influence the Navajo's decision to
      seek, accept, or reject the assistance of professional health care providers. In
      addition, some implications, strategies, and suggestions are included that may
      assist the nurse in improving the quality of care provided to the Navajo patient.

PMID- 7829857
TI  - Hispanic cultural health beliefs and folk remedies.
AB  - Cultural  awareness of health care practices and beliefs is increasing, but
      knowledge regarding Hispanic folk remedies and health care practices and beliefs
      is limited. This study used a focus group interview format for an open discussion
      of folk remedies and the health and illness practices of the participants. Eleven
      Hispanic women participated in a group interview that addressed the question, How
      do Hispanic health beliefs affect health care practices? Specifically, what
      actions are taken to treat symptoms of illness or injury? Qualitative data
      analysis of the 75 symptom and treatment statements was completed, and data were
      grouped according to symptom and complexity of treatments. This resulted in a
      rich compilation of remedies that Hispanics use in home treatments, with the
      emergence of a pattern comparable to the nursing process. This information adds
      to the current knowledge base of cultural health practices and provides a basis
      for continued research.

PMID- 7829858
TI  - Tibetan Buddhist medicine: a transcultural nursing experience.
AB  - Tibetan medicine, at 2,500 years old, is considered the oldest surviving medical
      tradition. A combination of logical healing practices, spiritual methods, and
      mystical practice, this tradition has a holistic basis as one of its foundational
      theories. It is known as the earliest form of mind-body medicine and can lend
      much of its wisdom to holistic and psychosomatic medicine and nursing, as well as
      the emerging field of psychoneuroimmunology. A basic overview of Tibetan
      medicine, coupled with a Western-educated nurse's experience during the care of a
      Tibetan Buddhist monk, provided an expanded view of the riches inherent in
      transcultural holistic nursing.

PMID- 7829859
TI  - Holistic nursing in New Zealand.
AB  - New Zealand nurses are active and dynamic emerging holistic practitioners.
      Despite an economic recession and dramatic changes in their health care delivery
      systems, the country's holistic nurses have mobilized to develop and begin a
      holistic nurses' association. Holistic nurses from both islands have begun
      independent practices using complementary therapies and modalities. Although New
      Zealand is distant from North America geographically, there have been increasing
      numbers of exchange visits and subsequent influence on international holistic
      nursing practice. New Zealand, being a lush, green, clean, semitropical country
      in the South Pacific, is a wonderful place for North American nurses to
      experience cross-cultural nursing while still being in an English-speaking
      country.

PMID- 7829860
TI  - Selective assay for CyPA and CyPB in human blood using highly specific anti
      peptide antibodies.
AB  - Cyclophilins A and B (CyPA and CyPB) are known to be the main binding proteins
      for cyclosporin A (CsA), a potent immunosuppressive drug. Due to the high
      homology between the two proteins, antibodies to CyPB were found to cross-react
      with CyPA. In order to avoid this phenomenon, we raised specific antibodies
      against peptides copying the most divergent parts of the two sequences. These
      antibodies allowed us to develop an ELISA capture assay selective for either
      isotype. Thus, we showed that leukocyte CyPB concentration was almost ten times
      lower than that of CyPA, and that in contrast to the results described in the
      literature, only CyPB was released in plasma. Moreover, CyPB levels in leukocytes
      and plasma were found to correlate for the same donor, but no relationship was
      found with CyPA level.

PMID- 7829861
TI  - Biotin-avidin immobilization of platelet glycoproteins (BAIPG): a new capture
      assay for the detection of anti-platelet antibodies.
AB  - Several 'capture' assays are currently employed to identify specific platelet
      antibodies, but all require the use of murine monoclonal antibodies (MoAbs)
      against the antigen of interest. We have developed a new antigen capture assay
      for the detection of platelet reactive antibodies, based on platelet surface
      sialoglycoprotein labelling with biotin hydrazide, and a following immobilization
      of the biotinylated platelet proteins to microtiter wells that had been coated
      with streptavidin. The resulting solid phase can then be used in a simple ELISA
      to detect serum and platelet associated antibodies. We describe here two versions
      of this biotin-avidin immobilization of platelet glycoproteins (BAIPG) assay. In
      BAIPG assay type I, the test sera are directly incubated in microtiter wells
      previously coated with streptavidin plus biotinylated platelet proteins. The
      BAIPG type II procedure involves the incubation of sera with biotinylated
      platelets before platelet solubilization, and, after platelet lysis, the
      immobilization of the immune complexes to streptavidin-coated wells. In both
      cases, the bound antibodies are determined by alkaline phosphatase conjugated
      anti-human IgG. Using BAIPG type I, positive results were obtained in 7/33
      patients with idiopathic thrombocytopenic purpura (ITP), 1/10 patients with
      secondary immune thrombocytopenia (SIT) and 4/17 with non-immune thrombocytopenia
      (NIT). The BAIPG type II test was positive in 13 out of 33 patients with ITP, in
      six out of ten patients with SIT, and in three out of the 17 patients with NIT. A
      comparison between BAIPG and monoclonal antibody immobilization of platelet
      antigens (MAIPA) assays showed a high degree of correlation between the two
      methods. These results suggest that the BAIPG assay is a valuable new tool for
      the detection of anti-platelet antibodies.

PMID- 7829862
TI  - Programmed differentiation of murine thymocytes during fetal thymus organ
      culture.
AB  - Fetal thymus organ culture (FTOC) has become widely used to investigate the
      impact of immunomodulators on T cell development. However, these studies have
      given variable results among different laboratories. In this study, we have found
      that fetal tissue age and mouse strain differences can affect the development of
      T cell phenotypes in this system. T cell development in FTOC occurred in two
      'waves', defined as peaks of cell recovery. The first wave consisted initially of
      CD4-CD8- double negative (DN) cells and CD4-CD8+ single positive (SP) T cells
      expressing gamma delta T cell receptor (TCR). CD4+CD8+ double positive (DP) cells
      expressing low levels of alpha beta TCR were produced soon thereafter; and these
      cells dominated the cultures for the balance of the first wave. Prolonged FTOC
      resulted in the production of another wave of T cells which were relatively
      enriched for CD4 or CD8 SP cells expressing high levels of alpha beta TCR, as
      well as DN cells and CD4-CD8+ SP T cells expressing high levels of gamma delta
      TCR. As defined by cell number and differentiation of alpha beta TCR SP cells,
      development was delayed in FTOC using fetal thymus tissue from younger fetuses
      relative to that observed when older fetal thymus tissue was used. The degree of
      development of T cells in FTOC was also strain dependent. Organ cultures derived
      from 14 gestation days (gd) C.B-17 scid/scid fetal thymus did not generate TCR
      bearing mature SP cells, but they did produce TCR-negative CD4 and CD8 SP cells
      likely to be precursors of DP thymocytes. Such cultures made from 18 gd tissue
      did not produce SP cells. Negative selection in FTOC was also evaluated. Mtv
      specific V beta 3 cells were deleted in FTOC of C3H/HeN tissue. Deletion occurred
      only in late FTOC, suggesting a late encounter between the Mtv deleting elements
      and susceptible T cells during ontogeny. These results show that while FTOC
      recapitulates normal thymic development by a variety of criteria, results can be
      influenced by the length of culture, as well as by the age and strain of fetal
      thymus tissue utilized.

PMID- 7829863
TI  - Stabilization and characterization of antigen-specific T suppressor inducer and T
      suppressor effector molecules.
AB  - H-2 specific T suppressor inducer (Tsfi) and T suppressor effector (Tsfe) factors
      show a dose-dependent inhibition of one-way mixed lymphocyte responses (MLR)
      between CBA/J responder spleen cells and C57BL/6 mitomycin C-treated stimulator
      spleen cells. The hydrophobic proteins Tsfi and Tsfe purified by ammonium sulfate
      precipitation and affinity methods were stabilized by the addition of Tris-saline
      pH 8 buffered octylglucopyranoside solution. The stabilized Tsfi and Tsfe
      fractions stored at 4 degrees C for 3-7 months retained a significant (> 72%)
      amount of their ability to inhibit MLR. Tsfi and Tsfe purified by salt
      precipitation and affinity methods were analyzed by SDS-PAGE. Enzyme-linked
      immunoassay (ELISA) and Western blots indicated that these molecules had T cell
      receptor (TcR) alpha chain, I-J, and IL-10 epitopes, but not TcR beta chain
      epitopes.

PMID- 7829864
TI  - A non-isotopic, highly sensitive, fluorimetric, cell-cell adhesion microplate
      assay using calcein AM-labeled lymphocytes.
AB  - A simple and sensitive cell-cell adhesion microplate assay was established using
      the cytoplasmic fluorescent dye, calcein AM. The procedure involves three steps:
      the labeling of lymphocytes with an adequate concentration of calcein AM (20
      microM) during a short incubation period (30 min); the adhesion of 2 x 10(5)
      labeled lymphocytes per well to confluent keratinocyte or fibroblast monolayers
      grown in microtiter plates for 90 min; and, finally, measurement of the
      fluorescent signal utilizing a new system of cold-light microfluorimetry (Rat,
      1993). During the adhesion assay, the release of calcein from labeled lymphocytes
      is low and the method permits the detection of as few as 1000 adherent cells.
      This non-radioactive procedure takes less than 4 h to perform and has proven to
      be as accurate and reliable as the common method using radioactive isotopes. In
      addition to its simplicity, the use of a fluorescent molecular probe in
      conjunction with cold-light microfluorimetry (CLF) offers many advantages of
      safety and economy, and can readily be adapted to the different cell types that
      participate in cell-cell adhesion.

PMID- 7829865
TI  - Metabolic radiolabelling of Mycoplasma gallisepticum on Vero cells and
      radioimmunoprecipitation assay.
AB  - A monoclonal antibody (MAb) A2 was produced against a major polypeptide of
      Mycoplasma gallisepticum with a molecular mass of 64 kDa. MAb A2 reacted in
      immunoblot at a titre of 10(4.33) and had a titre of 10(4.5) in an enzyme-linked
      immunosorbent assay. In a radioimmunoprecipitation assay (RIPA) using metabolic
      [35S]methionine radiolabelling of M. gallisepticum suspension in Vero cell
      culture, MAb A2 was able to precipitate the 64 kDa protein and another protein of
      47 kDa. The present study involving [35S]methionine labelling of M. gallisepticum
      in Vero cells represents a novel approach for labelling and characterizing the
      conformation-dependent mycoplasmal antigens in a RIPA system.

PMID- 7829866
TI  - Estimation of the protein-binding capacity of microplate wells using sequential
      ELISAs.
AB  - A non-linear mathematical method for estimating the protein binding capacity of a
      microwell is developed by applying Langmuir-type binding principles to data
      obtained from sequential ELISAs (Underwood and Steele (1991) J. Immunol. Methods
      142, 83). Experimental data from sequential ELISAs measuring the binding of
      rabbit and mouse immunoglobulin G and of BSA to Immulon 2 microwells agree well
      with the binding curves predicted by our simple mathematical model. Estimates of
      Immulon 2 microwell capacity for these proteins when coated in a 100
      microliters/well volume are between 250 and 325 ng/well. The method provides a
      convenient, quantitative method for estimating microwell capacity without the use
      of radioisotopes. A spreadsheet form of the method is also presented, so that the
      mathematical calculations for any set of experimental data may be performed
      readily using the spreadsheet's SOLVER function. The method is not applicable to
      data from experiments where significant desorption occurs or where binding to the
      solid phase deviates significantly from the simple Langmuir model.

PMID- 7829867
TI  - Improved fluorescent bioassay for the detection of tumor necrosis factor
      activity.
AB  - Tumor necrosis factor alpha (TNF-alpha) is a monokine of 17 kDa produced by
      activated macrophages and various cells involved in the immune system. We propose
      a new method for the measurement of TNF activity on mouse L929 fibroblast cells.
      After an incubation with TNF, the cells were stained with a solution of ethidium
      homodimer-1, a high-affinity red fluorescent DNA dye that is internalized only
      through altered cell membranes. The assay is sensitive, inexpensive and
      correlates with the already reported TNF assays while measuring the membrane
      alteration by TNF and not the cell detachment. It requires no rinsing before dye
      addition which may cause cell loss; there is no interference with culture medium
      components since the assay is performed in PBS. This method is more rapid and
      precise for routine measurement of TNF activity.

PMID- 7829868
TI  - Laboratory scale production of monoclonal antibodies in a tumbling chamber.
AB  - A simple device for laboratory scale production of monoclonal antibodies has been
      developed. Hybridomas were cultured in four individual dialysis tubes containing
      40-50 ml medium with 10% foetal calf serum, surrounded by 1.5-2 litres supply
      medium without any serum supplement. Once placed on a roller the special design
      of the apparatus leads to an eccentric rotation, thus keeping the cells in a
      stable homogeneous suspension. The system is automatically gassed, and this makes
      long term cultivation possible. Several hybridomas were tested over a culture
      period of at least 3 weeks, with supply medium changes every 3-4 days. Cell
      densities of up to 2.5 x 10(7)/ml and antibody concentrations of 0.3-1.9 mg/ml
      after purification were obtained. Results with this in vitro system allow a
      complete renunciation of the established in vivo method. The so called 'tumbling
      chamber' apparatus is easy to handle and to sterilize, is economic and
      universally adaptable in any research laboratory.

PMID- 7829869
TI  - Flow cytometric analysis of the granulocyte respiratory burst: a comparison study
      of fluorescent probes.
AB  - Chronic granulomatous disease (CGD) is a rare recessive disorder caused by
      defects in the NADPH oxidase enzyme complex of phagocytes (neutrophils,
      eosinophils and monocytes). CGD phagocytes fail to produce superoxide and other
      reactive oxygen species following cell activation (Malech, 1993). The products of
      oxidase activation can be measured in individual cells by flow cytometry using
      specific fluorescent probes that increase fluorescence upon oxidation (Trinkle et
      al., 1987). This approach can be used to confirm a diagnosis of CGD, and to
      detect the normal/abnormal phagocyte mixture that characterizes the X-linked CGD
      carrier state. Three fluorescent probes have been described as useful for this
      purpose: 2'7'-dichlorofluorescin diacetate (DCF) (Bass et al., 1983), 5,6-carboxy
      2'7'-dichlorofluorescein diacetate, bis(acetoxymethyl) ester (C-DCF) (Hockenbery
      et al., 1993) and dihydrorhodamine 123 (DHR) (Rothe et al., 1988; Kinsey et al.,
      1987). A direct comparison between these three probes has not been reported. In
      this study we performed a direct comparison between these three probes,
      evaluating their ability in flow cytometric analysis to maximize fluorescent
      separation between activated CGD patient and normal granulocytes. Using a whole
      blood technique with phorbol myristate acetate (PMA) as an activator, it was
      found that DHR loaded normal granulocytes had a fluorescence intensity which,
      upon activation, was 48-fold higher than that of C-DCF loaded granulocytes and
      seven-fold higher than DCF loaded granulocytes (P < 0.001). Use of sodium azide
      to decrease the catabolism of H2O2 enhanced the fluorescence of DCF by 140%, C
      DCF by 45% and DHR by 25%, suggesting that DCF is primarily sensitive to H2O2.
      DCF and DHR were then evaluated for sensitivity in the detection of small
      percentages of normal cells in a CGD/normal granulocyte mixture. Normal sub
      populations as small as 0.1% could clearly be distinguished using DHR, while DCF
      was insensitive at this level. Based on these findings, we used DHR in an effort
      to detect normal granulocytes in a CGD patient following therapeutic granulocyte
      transfusion. We were able to detect normal granulocytes in the circulation for up
      to 18 h after transfusion. With these data we show that DHR is the most sensitive
      flow cytometric indicator for the detection of oxygen reactive species in
      activated granulocytes and is the best probe for evaluating CGD patients and
      carriers. In addition, our data suggest that DHR is a useful tool for monitoring
      circulating normal granulocytes in CGD patients following transfusion, and
      potentially will be a sensitive probe for assessing the success of such future
      technologies as gene therapy for CGD.

PMID- 7829870
TI  - Development of a sandwich enzyme-linked immunosorbent assay for the determination
      of human heart type fatty acid-binding protein in plasma and urine by using two
      different monoclonal antibodies specific for human heart fatty acid-binding
      protein.
AB  - We have developed a sandwich enzyme-linked immunosorbent assay (ELISA) for the
      determination of human heart type fatty acid-binding protein (H-FABP) in human
      plasma and urine using the combination of two distinct monoclonal antibodies
      (MAbs) directed against human H-FABP purified from human heart muscle. The total
      assay time of the ELISA is practically much shorter than that of the competitive
      enzyme immunoassay (EIA) we previously reported. The immunoreactive mass of human
      H-FABP was specifically measured using a horseradish peroxidase (HRPO)-labeled
      anti-human H-FABP MAb as an enzyme-linked MAb, and anti-human H-FABP MAb
      immobilized on the polystyrene microtiter plate as a solid-phase MAb, and
      purified human H-FABP as standard materials. The assay range of the ELISA was 0
      250 ng/ml of plasma and urine. The ELISA yielded a coefficient of variation of
      less than 10% in inter- and intra-assays, and the good linearity was obtained in
      dilution test using clinical samples. Anticoagulants, except sodium fluoride and
      a high concentration of hemoglobin and bilirubin, did not interfere with the
      assay of plasma samples. A high concentration of hemoglobin, bilirubin and
      immunoglobulin, and contamination with seminal plasma did not interfere with the
      assay of urine samples. The average recovery of purified human H-FABP added to
      human plasma and urine samples was 98.5% and 97.0%, respectively. Myoglobin and
      myosin did not crossreact in the ELISA. The minimum detection limit of the ELISA
      was 1.25 ng/ml. The immunoreactive masses of human H-FABP in plasma and urine
      samples, obtained from one hundred normal healthy subjects were quantified by the
      sandwich ELISA. The normal mean (+/- SD) level of human H-FABP mass in plasma was
      3.65 +/- 1.81 ng/ml, and that in urine was 3.20 +/- 2.70 ng/ml. In conclusion,
      this sandwich ELISA is a useful tool for the sensitive and precise determination
      of human H-FABP in human plasma and urine, and it may be used specifically for
      clinical investigation and diagnosis of myocardial injury.

PMID- 7829871
TI  - Sustained production of human transferrin by transduced fibroblasts implanted
      into athymic mice: a model for somatic gene therapy.
AB  - Somatic gene therapy has been proposed as a means of treating inherited diseases
      involving defective or absent plasma proteins, viral diseases, and cancer.
      Introduction of the gene of interest into fibroblasts and implantation of these
      genetically modified fibroblasts using a skin equivalent system may be an
      attractive model for gene therapy because skin fibroblasts are easily obtained
      and propagated in culture. This study evaluated expression of the gene for human
      transferrin (hTf) by genetically modified fibroblasts in vitro and in vivo. NIH
      3T3 fibroblasts, which form non-metastasizing tumors in athymic mice, were
      transduced with a retroviral vector encoding hTf. The transduced cells were
      cloned by limiting dilution and hTf production by the cloned cells measured. Two
      clones of cells producing high levels of hTf were used to seed collagen-coated
      nylon matrices, which were maintained in culture for up to 53 d. The rate of
      synthesis of hTf by the seeded matrices was constant after 22 d in vitro.
      Matrices seeded with cloned, transduced cells were implanted subcutaneously into
      seven athymic mice, and plasma levels of hTf were assessed biweekly. In all
      animals, the plasma level of hTf was detectable at week 6 after implantation.
      Levels of hTf remained elevated in the animals until the implants were removed at
      week 12. At week 10, the level of hTf in the plasma correlated with tumor volume
      in tumors less than 2000 mm3 in size. The half-life of hTf in the mice was 39.5
      h. In this model, gene expression did not decline for the 12-week observation
      period.

PMID- 7829872
TI  - Specific suppression of lupus-like graft-versus-host disease using extracorporeal
      photochemical attenuation of effector lymphocytes.
AB  - (C57BL/6 x DBA/2)F1 (B6D2F1) mice inoculated with parental DBA/2 (D2) splenocytes
      develop chronic stimulatory graft-versus-host reaction with many of the clinical
      manifestations of systemic lupus erythematosus. This investigation tested the
      ability of 8-methoxypsoralen (8-MOP) and ultraviolet A (UVA) light-treated D2
      cells, primed to contain an expanded population of T cells specific for B6D2F1
      major histocompatability complex antigens, to treat and/or prevent such systemic
      lupus erythematosus-like disease. 8-MOP/UVA-treated cells from B6D2F1-primed D2
      donors were inoculated into B6D2F1 recipients weekly six to ten times, either
      before or after initiating graft-versus-host disease with normal D2 cells. A
      third group of B6D2F1 recipients were vaccinated weekly six times before disease
      initiation using 8-MOP/UVA-attenuated, B6D2F1-primed D2 cells that had been
      secondarily stimulated and expanded in vitro in the presence of irradiated B6D2F1
      targets and interleukin-2. Control B6D2F1 mice were vaccinated with 8-MOP/UVA
      treated D2 cells stimulated in vitro and/or in vivo with (C3H/HeJ x DBA/2)F1
      cells. Only mice vaccinated with 8-MOP/UVA-attenuated D2-anti-B6D2F1 cells that
      were secondarily stimulated and expanded in vitro exhibited differences from
      controls when measured by the clinical parameters of ascites formation, and mean
      survival (p < 0.025). These groups also differed significantly in mean
      antinuclear antibody titer measured 14 weeks after disease initiation (p < 0.05).
      At 28 weeks, histologic evidence of systemic lupus erythematosus-like kidney
      disease was found only in the control group. These results indicate that
      photochemically attenuated D2-anti-B6D2F1 cells primed in vivo and secondarily
      stimulated and expanded in vitro are capable of vaccinating recipients against
      progression of graft-versus-host reaction-initiated systemic lupus erythematosus
      like disease.

PMID- 7829873
TI  - Methotrexate therapy of psoriasis: differential sensitivity of proliferating
      lymphoid and epithelial cells to the cytotoxic and growth-inhibitory effects of
      methotrexate.
AB  - Although methotrexate (MTX) is one of the most clinically effective therapies
      employed to treat psoriasis, the mechanism by which low-dose MTX acts to modulate
      the hyperplasia of psoriasis, leading to the restoration of clinically normal
      skin, is only partially understood. MTX has been considered a cytotoxic agent
      that mediates its effect primarily on proliferating or cycling epidermal cells.
      Recently, proliferating lymphoid cells have been identified in psoriatic lesions,
      raising the possibility that proliferating lymphoid cells could be another target
      cell that is killed by MTX. In this study, we examined the growth-inhibitory and
      cytotoxic effects of MTX on proliferating lymphoid cells [THP-1 (macrophage), and
      MOLT-4 (T cell)], epithelial cells (HeLa, and HaCat), and normal human
      keratinocytes (NHK) in vitro. The proliferating cells were exposed to MTX for 24
      h, and placed in fresh media to mimic the transient MTX blood levels that result
      from once-weekly therapy. THP-1 and MOLT-4 were found to be 10-100 times more
      sensitive to the cytotoxic effects of MTX than were HeLa and HaCat, and more than
      1000 times more sensitive than primary human keratinocytes. At MTX concentrations
      that would be expected to occur in vivo during once-weekly therapy, a large
      percentage (> 95%) of proliferating lymphoid targets would be killed, and only a
      small percentage (< 10%) of proliferating epidermal cells would be affected. This
      in vitro data suggests that in psoriasis proliferating lymphoid cells are more
      likely than epithelial cells to be a major cellular target of MTX in vivo.

PMID- 7829874
TI  - Levels of skin-derived antileukoproteinase (SKALP)/elafin in serum correlate with
      disease activity during treatment of severe psoriasis with cyclosporin A.
AB  - The epidermal serine proteinase inhibitor SKALP (also known as elafin), directed
      against human leukocyte elastase and proteinase 3, is strongly induced in
      suprabasal keratinocytes during inflammation. The presence of SKALP/elafin in
      urine has been demonstrated for several inflammatory skin disorders, such as
      psoriasis, erythroderma, and erysipelas. In this study we investigated whether
      SKALP/elafin levels in serum and urine of psoriatic patients can be used as a
      marker for disease activity during treatment. Patients with severe chronic
      disabling psoriasis were treated for 16 weeks with cyclosporin A, which resulted
      in a marked clinical improvement as measured with the PASI score. SKALP/elafin
      levels both in serum and urine were determined with an enzyme-linked
      immunosorbent assay (ELISA). Measurements were performed at the start of the
      cyclosporin A treatment, and after regular intervals up to 16 weeks. The results
      indicate that 1) SKALP/elafin determination in serum rather than in urine is the
      preferred method, because the decrease in serum SKALP levels during therapy is
      more pronounced and correlated better with the clinical course of the patients;
      2) SKALP/elafin levels in serum decreased during cyclosporin A treatment (p <
      0.05); and 3) SKALP/elafin levels in serum correlate with the PASI score (p <
      0.01). We conclude that SKALP/elafin measurement in serum of patients with severe
      psoriasis provides a tool for monitoring disease activity.

PMID- 7829875
TI  - Singlet oxygen may mediate the ultraviolet A-induced synthesis of interstitial
      collagenase.
AB  - Singlet oxygen has been postulated to be generated by Ultraviolet (UV) A
      irradiation of mammalian cells. We studied the role of singlet oxygen in the
      downstream signaling of the complex UV response leading to the induction of
      matrix-metalloproteinase-1 (interstitial collagenase/MMP-1). Exposure of cultured
      human fibroblasts to singlet oxygen, generated in a dark reaction by
      thermodissociation of the endoperoxide of the disodium salt of 3,3'-(1,4
      naphthylidene) dipropionate (NDPO2) induced collagenase mRNA steady state levels
      in a dose dependent manner. The increase in collagenase expression after singlet
      oxygen exposure generated with 3 mM NDPO2 was equivalent to that observed with
      UVA at a dose rate of 200-300 kJ/m2 and developed in a similar time course. In
      contrast, mRNA levels of TIMP-1, the specific tissue inhibitor of
      metalloproteinases, remained unchanged. Indirect evidence for the role of singlet
      oxygen in the UVA induction of collagenase comes from studies using singlet
      oxygen enhancer or quencher. Accordingly, incubation in deuterium oxide, an
      enhancer of singlet-oxygen lifetime, led to an additional increase in steady
      state levels of collagenase mRNA after exposure to NDPO2 or to UVA irradiation.
      In contrast, sodium azide, a potent quencher of singlet oxygen, almost totally
      abrogated the induction of collagenase after exposure of fibroblasts to NDPO2 or
      to UVA irradiation. Similar results were obtained in studies of the proteins by
      radioimmunoprecipitation of MMP-1 and TIMP-1 using specific antibodies.
      Collectively, our data provide circumstantial evidence that singlet oxygen
      mediates the UVA induction of collagenase in vitro, whereas it does not exert any
      effect on TIMP-1 synthesis. The unbalanced synthesis of interstitial collagenase
      may contribute to the connective tissue damage in vivo related to photoaging and
      other photocutaneous disorders.

PMID- 7829876
TI  - The pancornulins: a group of small proline rich-related cornified envelope
      precursors with bifunctional capabilities in isopeptide bond formation.
AB  - In this report, the pancornulins are identified as members of the spr (small,
      proline-rich) multigene family by amino acid sequence and mass spectrometry
      analyses. One of the pancornulins (14.9 kDa) is identical to the protein
      predicted by spr-1 clone 128. The other pancornulins (16.9 kDa and 22 kDa) are
      novel members of the spr family. Immunoelectron microscopy of purified cornified
      envelopes with a pancornulin-specific antibody established these proteins more
      definitively as cornified envelope precursors. In addition, two-dimensional
      electrophoretic analyses of keratinocyte extracts labeled enzymatically with
      dansylcadaverine (to identify amine acceptors) or dansylPGGQQIV (to identify
      amine donors) showed that both glutamine and lysine residues within the
      pancornulins participate in the isopeptide linkage characteristic of cornified
      envelope formation. These results contrasted with those obtained using
      involucrin, a prominent cornified envelope protein shown capable of acting only
      as an amine acceptor in this system. Novel partial cDNAs obtained after reverse
      transcription and polymerase chain reaction amplification of total messenger RNA
      with pancornulin-specific primers suggest that the spr multigene family may be
      even larger than previously described. The bifunctional reactivity of the
      pancornulins in cross-linking and the large number of family members identified
      to date suggest that the pancornulins and other spr-1-related proteins may be
      more important in cornified envelope formation than previously considered,
      perhaps functioning as "bridge" molecules during the early phases of cornified
      envelope assembly.

PMID- 7829877
TI  - Characterization of two distinct calcium-binding sites in the amino-terminus of
      human profilaggrin.
AB  - Profilaggrin is a large phosphorylated protein (approximately 400 kDa in humans)
      that is expressed in the granular cells of epidermis where it forms a major
      component of keratohyalin. It consists of multiple copies of similar filaggrin
      units plus amino- and carboxy-terminal domains that differ from filaggrin.
      Proteolytic processing of profilaggrin during terminal differentiation results in
      the removal of these domains and generation of monomeric filaggrin units, which
      associate with keratin intermediate filaments to form macrofibrils in the stratum
      corneum. The amino-terminal domain contains two calcium-binding motifs similar to
      the EF-hands found in the S-100 family of calcium-binding proteins. In this
      report, we expressed the 293-residue amino-terminal pro-domain of human
      profilaggrin as a polyhistidine fusion protein in Escherichia coli, and
      characterized calcium binding by a 45Ca++ binding assay and fluorescence emission
      spectroscopy. Fluorescence measurements indicated that the profilaggrin
      polypeptide undergoes conformational changes upon the removal of Ca++ with
      ethylenediamine tetraacetic acid, demonstrating the presence of two calcium
      binding sites with affinities for calcium that differ ninefold (1.4 x 10(-4) M
      and 1.2 x 10(-3) M). We suggest that this functional calcium-binding domain at
      the amino-terminus of human profilaggrin plays a role in profilaggrin processing
      and in other calcium-dependent processes during terminal differentiation of the
      epidermis.

PMID- 7829878
TI  - Retinoic acid regulates oral epithelial differentiation by two mechanisms.
AB  - The effect of retinoic acid (RA) concentration on differentiation of oral
      keratinocytes and the influence of fibroblasts on RA-dependent regulation were
      investigated in a lifted culture system. Keratinocyte differentiation was
      assessed by morphology, immunohistochemistry and immunoblotting.
      Filaggrin/profilaggrin and keratin 1 were used as biochemical markers for
      cornified epithelium and keratins 13 and 19 as markers for noncornified
      epithelium. Cultured oral keratinocytes in RA-free conditions differentiated in a
      manner that closely resembled the differentiation pattern of gingival epithelia
      in vivo. Increasing RA concentrations altered the in vivo-like terminal
      differentiation of oral keratinocytes by disruption of organized stratification,
      inhibition of filaggrin/profilaggrin and K1 expression, and stimulation of K13
      and K19 expression. Differentiation of keratinocytes from both cornified and
      noncornified regions of the oral cavity varied in a similar manner in response to
      added RA, with the exception of K19 expression. K19 was consistently expressed at
      higher levels in keratinocytes originating from noncornified epithelia as
      compared to those from cornified epithelia. The level of RA regulation was
      ultimately dependent on the type of fibroblasts underlying the epithelial cells.
      Homologous fibroblasts rendered the oral keratinocytes less sensitive to the
      effects of RA than skin fibroblasts. In addition, at a given RA concentration,
      fibroblasts from cornified oral mucosa potentiated keratinocyte expression of RA
      sensitive markers of keratinization as compared to the influence exerted by
      fibroblasts originating from noncornified oral mucosa. These results indicate
      that the RA regulation of oral epithelial differentiation is mediated by two
      separate mechanisms: a direct, RA concentration-dependent effect, and an
      indirect, fibroblast-mediated effect.

PMID- 7829879
TI  - Tissue inhibitor of metalloproteinases-1 is decreased and activated gelatinases
      are increased in chronic wounds.
AB  - The balance between matrix deposition and tissue turnover is fundamental in wound
      healing. It is likely that the balance between proteolytic enzymes and their
      inhibitors contributes to this balance. Matrix metalloproteinases are clearly
      important in tissue turnover, but their roles in wound healing are poorly
      understood. To investigate this, fluid from healing wounds resulting from
      mastectomies was collected from 1 h to 10 d post-surgery, and was analyzed for
      tissue inhibitor of metalloproteinases-1 concentrations. In all cases, tissue
      inhibitor of metalloproteinases-1 levels were initially comparable to those in
      serum, but increased rapidly to significantly higher levels within two days, with
      a tenfold average increase for five patients. On the other hand, zymography
      revealed that gelatinase A (72 kDa) levels increased moderately, whereas
      gelatinase B levels (92 kDa) decreased an average of twofold within 4 d. In
      contrast, fluid from chronic wounds had significantly more gelatinolytic
      activity, including lower-molecular-weight proteinase species that may represent
      activated or superactivated gelatinase fragments, as suggested by
      immunoprecipitation with specific antibodies. Tissue inhibitor of
      metalloproteinases-1 levels were lower in chronic than in healing wounds. These
      data may indicate that excess proteolysis in chronic wounds retards successful
      healing, and results from an imbalance of proteinase and inhibitors, as well as
      the presence of higher levels of activated metalloproteinases.

PMID- 7829880
TI  - Glucocorticoid regulation of elastin synthesis in human fibroblasts: down
      regulation in fibroblasts from normal dermis but not from keloids.
AB  - Keloids arise as benign connective tissue masses at sites of injury in
      genetically predisposed individuals. In addition to excessive collagen
      accumulation, there is biochemical and histologic evidence of elastic tissue.
      Previous studies showed that glucocorticoid regulation of collagen synthesis
      differs in fibroblasts from normal adult dermis and keloids. To define further
      the abnormal regulation of matrix synthesis in keloid fibroblasts, we examined
      glucocorticoid regulation of elastin synthesis. The basal level of elastin
      synthesis was significantly higher in keloid than in normal cells, and
      hydrocortisone reduced synthesis of elastin and elastin mRNA in normal but not in
      keloid fibroblasts. We had shown previously that fibroblasts from fetal dermis
      resembled keloid fibroblasts in glucocorticoid regulation of growth and collagen
      synthesis. In this study, glucocorticoids failed to down-regulate elastin
      synthesis in fetal cells that had not differentiated to produce normal levels of
      elastin, whereas fetal cells with normal elastin production exhibited
      glucocorticoid down-regulation. Abnormal regulation in keloid cells was
      independent of cell density and was confined to fibroblasts cultured from the
      keloid nodule. These findings reinforce the conclusion that a matrix-regulatory
      pathway is deranged in these focal lesions. Coordinate down-regulation of
      collagen and elastin by hydrocortisone in normal adult dermal fibroblasts and the
      failure of hydrocortisone to down-regulate synthesis of either protein in keloid
      cells support the existence of common elements in the regulatory pathways of
      these two matrix proteins.

PMID- 7829881
TI  - Apolipoprotein E deficiency leads to cutaneous foam cell formation in mice.
AB  - Apolipoprotein E deficiency leads to familial dysbetalipoproteinemia
      characterized by increases in serum lipid levels, atherosclerosis, and cutaneous
      xanthoma. Apolipoprotein E is synthesized in many tissues in the body, including
      the epidermis. In the present study, we determined whether transgenic mice
      deficient in apolipoprotein E develop cutaneous xanthoma and the effect of
      dietary fat intake on these lesions. We also determined whether apolipoprotein E
      deficient mice have abnormalities in cutaneous barrier function or stratum
      corneum structure. Homozygous apolipoprotein E-deficient mice (-/-) fed a high
      fat diet displayed a diffuse inflammatory infiltrate in the dermis surrounding
      fat droplets in macrophages. In homozygous mice (-/-) fed a low-fat diet, similar
      lesions were seen but they tended to be focal and less prominent. In heterozygous
      mice (+/-) fed the high-fat diet, a few inflammatory cells were present in the
      dermis but foam cells were not seen. Control mice (+/+) fed a high-fat diet
      displayed scattered inflammatory cells in the dermis. Heterozygous mice (+/-) fed
      a low-fat diet were similar to control mice (+/+) fed a low-fat diet. The extent
      of foam cell formation correlated directly with the degree of atherosclerosis.
      There were no abnormalities in permeability-barrier function or stratum corneum
      structure in apolipoprotein E-deficient mice. Thus, the lack of apolipoprotein E
      production in the epidermis does not appear to lead to any detectable abnormality
      in structure or function of the stratum corneum. However, lack of apolipoprotein
      E leads to cutaneous foam cell formation, presumably secondary to disturbances in
      lipoprotein metabolism.

PMID- 7829882
TI  - Epidermal fatty acid oxygenases are activated in non-psoriatic dermatoses.
AB  - The extent of epidermal fatty acid oxygenase activation in non-psoriatic
      dermatoses and the nature of these oxygenases are not known. The monohydroxylated
      fatty acid derivatives produced in vivo and trapped in skin scales or produced in
      vitro by oxygenases preserved in scales were analyzed by high performance liquid
      chromatography in 10 patients with non-psoriatic dermatoses. Evidence for 15
      lipoxygenase activation included the finding of 15(S)-hydroxyeicosatetraenoic
      acid (HETE) in scales from seven patients and the production of 15(S)-[14C]HETE
      and 13(S)-[14C]hydroxyoctadecadienoic acid (HODE) during scale incubations,
      respectively, with [14C]arachidonic and [14C]linoleic acid. Evidence for the
      activation of an arachidonic acid 12(R)-oxygenase included the finding of 12(R)
      HETE in scales from eight patients and the production of 12(R)-[14C]HETE during
      scale incubations with [14C]arachidonic acid. 13-HODE was the predominant fatty
      acid derivative present in scale extracts; its lack of enantiopurity (mean S/R =
      3.1) and the substantial formation of 9-HODE (mean S/R = 0.6; 9/13-HODE = 0.43)
      suggest its derivation from 15-lipoxygenase and a second oxygenase. The levels of
      15(S)-HETE and 12(R)-HETE had a 125- to 144-fold range and were highest in scales
      from a patient with erythroderma and in three psoriatic scale samples similarly
      analyzed. These findings indicate that 15-lipoxygenase, most likely of
      keratinocyte origin, and an arachidonic acid 12(R)oxygenase of unknown type and
      cell origin are activated in diverse dermatoses.

PMID- 7829883
TI  - Integrin expression by human epidermal keratinocytes can be modulated by
      interferon-gamma, transforming growth factor-beta, tumor necrosis factor-alpha,
      and culture on a dermal equivalent.
AB  - Receptors of the integrin family are largely confined to the basal layer of
      keratinocytes, both in human epidermis and in stratified cultures of human
      keratinocytes. However, suprabasal integrin expression is observed during
      epidermal wound healing and in psoriatic lesions. We have investigated potential
      stimuli of suprabasal expression. Addition of transforming growth factor-beta
      (TGF-beta), interferon-gamma (IFN-gamma), or tumor necrosis factor-alpha (TNF
      alpha) to keratinocytes cultured with a 3T3 feeder layer did not induce
      suprabasal expression. The cytokines caused small changes in the levels of alpha
      2 beta 1 or alpha 3 beta 1 on the surface of basal keratinocytes but had no
      significant effect on the proportion of cells adhering to fibronectin, type IV
      collagen, and laminin, and did not cause changes in the mobility of integrin
      subunits on polyacrylamide gels. Injection of TNF-alpha or IFN-gamma
      intradermally into healthy human volunteers induced an inflammatory response but
      did not induce suprabasal integrin expression. However, we did observe transient
      suprabasal integrin expression when keratinocytes were grown on a dermal
      equivalent consisting of fibroblasts in a collagen gel. One week after raising
      the cultures to the air-liquid interface, beta 1 integrins were found in all the
      viable cell layers, with suprabasal cells co-expressing integrins and involucrin;
      1 week later integrins were confined to the basal layer. Addition of TGF-beta,
      IFN-gamma, or TNF-alpha to the dermal equivalents neither induced nor inhibited
      suprabasal integrin expression. We conclude that suprabasal integrin expression
      is not induced by the inflammatory cytokines tested, and instead may reflect the
      proliferation/differentiation status of the epidermis.

PMID- 7829884
TI  - Polarized expression and basic fibroblast growth factor-induced down-regulation
      of the alpha 6 beta 4 integrin complex on human microvascular endothelial cells.
AB  - Endothelial cells rest on a basement membrane that anchors them to the vessel
      wall. The alpha 6 beta 4 integrin complex has been described on epithelial cells,
      frequently localizes to basement-membrane structures, and appears to play a role
      in binding epithelial cells to laminin. We have determined that human
      microvascular endothelial cells express the beta 4 integrin chain in vivo and
      that it preferentially localizes to the endothelial basement membrane. Human
      microvascular endothelial cells and human umbilical vein endothelial cells also
      express cell-surface beta 4 in vitro. In addition, the expression of beta 4
      appears to be polarized to the undersurface of endothelial cell monolayers in
      vitro, mimicking its in vivo localization. Stimulation of microvascular
      endothelial cells with basic fibroblast growth factor or phorbol 12-myristate 13
      acetate, agents previously shown to induce endothelial cell migration in vitro,
      resulted in a marked decrease in cell-surface expression of the beta 4 integrin
      chain, associated with a decrease in beta 4 mRNA. These data demonstrate that
      human endothelial cells express the beta 4 integrin chain in vivo and in vitro,
      the expression of this integrin chain is polarized, and its expression is
      regulated on microvascular endothelial cells by factors important in wound
      healing and vascular regeneration.

PMID- 7829885
TI  - Epithelial differentiation fails to support replication of cloned human
      papillomavirus type 16 DNA in transfected keratinocytes.
AB  - Research on the life cycle of human papillomaviruses (HPVs) has suffered from the
      lack of a model system that allows the use of molecularly cloned HPV DNA. In this
      study, we analyzed replication of molecularly cloned HPV-16 genomes after
      transfection into cells of two human keratinocyte cell lines. Transfected cells
      were grown in cell culture (in vitro) or in transplantation chambers on the
      flanks of nude mice (in vivo). When DNA was extracted after different time
      intervals, replication of HPV-16 DNA could not be detected. Even the formation of
      a stratified epithelium under in vivo conditions failed to support vegetative
      replication. In contrast, transfection of molecularly cloned HPV-11 DNA resulted
      in replication of viral DNA in vitro. It seems likely that besides epithelial
      cell differentiation, a number of other factors influence HPV-16 replication.

PMID- 7829886
TI  - Sunscreens and T4N5 liposomes differ in their ability to protect against
      ultraviolet-induced sunburn cell formation, alterations of dendritic epidermal
      cells, and local suppression of contact hypersensitivity.
AB  - Exposure of skin to ultraviolet (UV) radiation can lead to diverse biologic
      effects, including inflammation, sunburn cell formation, alterations of cutaneous
      immune cells, and impaired induction of contact hypersensitivity responses. The
      molecular mechanisms of these UV-induced effects are not completely understood.
      We investigated the ability of sunscreens and liposomes containing the DNA
      excision repair enzyme T4 endonuclease V to prevent these effects of UV
      radiation. The use of T4N5 liposomes, which increase the repair of cyclobutyl
      pyrimidine dimers, provides an approach for assessing the role of DNA damage in
      the effects of UV radiation on the skin. Exposing C3H mice to 500 mJ/cm2 UVB
      radiation from FS40 sunlamps resulted in skin edema, sunburn cell formation, and
      morphologic alterations and decreased numbers of Langerhans cells and Thy-1+
      dendritic epidermal T cells. In addition, the induction of contact
      hypersensitivity after application of 2,4-dinitrofluorobenzene on UV-irradiated
      skin was diminished by 80%. Applying sunscreens containing octyl-N-dimethyl-p
      aminobenzoate, 2-ethylhexyl-p-methoxycinnamate, or benzophenone-3 before this
      dose of UV irradiation gave nearly complete protection against all of these
      effects of UV irradiation. In contrast, topical application of T4N5 liposomes
      after UV irradiation had no effect on UV-induced skin edema and only partially
      protected against sunburn cell formation and local suppression of contact
      hypersensitivity, although its ability to protect against alterations in
      dendritic immune cells was comparable to that of the sunscreens. These results
      suggest that DNA damage is involved in only some of the local effects of UV
      radiation on the skin. In addition, T4N5 liposomes may be a useful adjunct to
      sunscreens because they can reduce some of the deleterious effects of UV
      radiation on skin even after a sunburn has been initiated.

PMID- 7829887
TI  - Human Langerhans cells express E-cadherin.
AB  - Murine Langerhans cells (LC) synthesize and express E-cadherin, a Ca(++)
      dependent homophilic cell adhesion molecule that mediates LC-keratinocyte (KC)
      binding in vitro. In vivo, E-cadherin expression by LC may promote localization
      and persistence of LC within the epidermis through LC-KC adhesion. In addition,
      changes in LC E-cadherin expression or affinity may be an important factor in the
      egress of LC from the epidermis after exposure to antigen. The aim of the present
      study was to determine if human LC also express E-cadherin. Suction blister roofs
      were obtained from normal volunteers and epidermal cell (EC) suspensions were
      prepared by limited trypsinization in the presence of 1 mM Ca++. EC were then
      incubated with antibodies to E-cadherin and CD1a or HLA-DR, and examined by two
      color analytical flow cytometry or immunofluorescence microscopy. Most (82.9% +/-
      7.4% [mean +/- SD], range 67-89%, n = 7) freshly prepared human LC expressed E
      cadherin, as did the majority of KC. The amount of E-cadherin (as determined by
      mean fluorescence intensity) expressed by LC and KC was similar. Trypsin/EDTA
      treatment of freshly prepared EC abrogated expression of E-cadherin by LC and KC,
      whereas E-cadherin was not degraded by trypsin in the presence of Ca++. LC
      expressed lower levels of E-cadherin after 3 d in culture. Thus, human LC, like
      murine LC, express the homophilic adhesion molecule E-cadherin, which may be
      important in establishing and maintaining interactions between LC and KC in
      mammalian epidermis.

PMID- 7829888
TI  - Mechanism of human polymorphonuclear leukocyte adhesion to serum-treated
      corneocytes.
AB  - The accumulation of polymorphonuclear leukocytes (PMN) beneath the stratum
      corneum is a characteristic histopathologic finding in various aseptic pustular
      dermatoses. To elucidate the pathomechanism involved in this phenomenon, we
      investigated whether PMN also attach to a sheet of corneocytes in vitro. A 1-cm2
      corneocyte sheet was attached to a sterile glass slide with double adhesive tape
      used for skin graft surgery before incubating with human serum. The PMN
      suspension then was applied to the sheet. Attached cells were stained with May
      Grunwald-Giemsa and counted with a computer image analyzer. We quantitatively
      assessed PMN adhesion to the serum-treated corneocyte sheets, which was mediated
      by activation of the alternative complement pathway. Addition of either anti-CD18
      or anti-CD11b antibody to the assay system resulted in a marked reduction of PMN
      adhesion. We also demonstrated immunohistochemically that iC3b was formed on the
      serum-treated corneocytes. These findings suggest that PMN attach to serum
      treated corneocytes through an interaction of CR3 expressed on PMN with iC3b
      coated corneocytes. In addition, we found that this adhesion was enhanced by
      activation of PMN with phorbol myristate acetate. From these results, we
      speculate that complement activation by corneocytes occurs in the cutaneous
      lesions of aseptic pustular dermatoses and that PMN can be stimulated by the
      interaction with iC3b-opsonized corneocytes as well as by chemotaxins, leading to
      damage of the surrounding epidermal keratinocytes.

PMID- 7829889
TI  - Comparative epidemiology of pemphigus in Tunisia and France: unusual incidence of
      pemphigus foliaceus in young Tunisian women.
AB  - Recent studies have suggested that in Tunisia, pemphigus foliaceus is more
      frequent in young women than expected. To confirm these findings, we compared the
      incidence rates of pemphigus in Tunisia as a whole and in a large area of France.
      New cases of pemphigus were detected retrospectively from dermatology departments
      and pathology laboratories over a 6-year period and classified as pemphigus
      vulgaris or foliaceus according to the pathology. In France, the incidence rate
      was 1.7 cases per million per year (95% confidence interval 1.4 to 2.1).
      Pemphigus vulgaris accounted for 73% of all cases, incidence increased with age,
      and the female-to-male sex ratio was 1.2. The incidence rate was significantly
      higher in Tunisia than in France: 6.7 cases per million per year (95% confidence
      interval 5.8 to 7.7); pemphigus foliaceus was more frequent (61%), the female-to
      male sex ratio was 4.1, and the incidence rate was higher in young women. The
      incidence rate was 15.5 cases per million per year for pemphigus foliaceus among
      women aged 25 to 34 years and was even higher in some rural areas. No case was
      observed among household members or in neonates, and only one case occurred in
      childhood. Thus, we confirmed that the epidemiology of pemphigus in Tunisia is
      unusual. High rates of pemphigus foliaceus among young people living in rural
      areas are reminiscent of Brazilian pemphigus. However, the absence of cases among
      genetically related household members and during childhood, and the large
      predominance of women, contrast with Brazilian pemphigus.

PMID- 7829890
TI  - Exclusion of interleukin-1 receptor antagonist as a primary disease determinant
      for psoriasis.

PMID- 7829891
TI  - Description of a new monoclonal antibody, FC-2.15, reactive with human breast
      cancer and other human neoplasias.
AB  - FC-2.15 is an IgM monoclonal antibody (MAb) obtained by immunizing Balb/c mice
      with tumor epithelial cells from a human undifferentiated primary breast
      carcinoma. FC-2.15 reacts with 93.9% (31/33) of human breast primary tumors,
      independently of their histology and hormone receptor content. Moreover, FC-2.15
      reacts with 79.6 +/- 13.8% (mean +/- SD) of total breast malignant tumor cells
      and with 88.7 +/- 9.9% of proliferating tumor cells. It recognizes other
      neoplasia such as colon cancer, squamous carcinoma and melanoma. Among the normal
      tissues examined, strong cross-reactivity was found with kidney proximal
      convolute tubules, bone marrow myeloid progeny, peripheral granulocytes and large
      bowel epithelium. Through Western blots, FC-2.15 recognizes three major bands of
      Mr 160 kDa, 130 kDa and 115 kDa in membrane extracts of MCF-7 cells grown in nude
      mice and of human breast carcinoma and three major bands of 250 kDa, 185 kDa and
      105 kDa in membrane extracts of peripheral granulocytes. This MAb mediates
      complement- cytotoxicity against malignant cells, reducing the clonogenic
      capacity of breast primary tumor cells and MCF-7 cells to 35.6 +/- 41.2% and 11.7
      +/- 4.8% of control values respectively, whereas that of normal bone marrow cells
      is not affected (104.7 +/- 17.4%).

PMID- 7829892
TI  - Evaluation of critical differences of CEA and CA 15.3 levels in serial samples
      from patients operated for breast cancer.
AB  - In the present investigation we evaluated the variability of tumor marker levels
      in the follow-up of patients without evidence of disease after resection of
      primary breast cancer. CEA and CA15.3 were measured using commercially available
      methods in serial blood samples collected from 170 patients. The coefficient of
      variation among all samples from each patient, which accounts for the total
      variability (analytical variability+biological variability), was widely scattered
      (from 4 to 99% for CEA; from 4 to 52% for CA15.3). The critical difference was
      calculated using the formula designed by Fraser [CD = 2.77. (CVa2 + CVb2)1/2]. It
      ranged from 11 to 276 for CEA and from 11 to 144 for CA15.3. From the present
      findings we conclude that: 1) it is possible to identify individually tailored
      decision criteria to evaluate tumor marker variations in the follow-up of breast
      cancer patients; 2) in a considerable number of cases the non-tumor-related
      variability is too high to allow the early identification of minor tumor marker
      variations that are of clinical relevance.

PMID- 7829893
TI  - Evaluation of the expression of tissue DF-3 and MCA and the corresponding serum
      values in patients with breast carcinoma.
AB  - Two specific monoclonal antibodies for breast tissue (DF3 and MCAb-12) and the
      corresponding tumor markers CA15-3 and MCA in serum have been evaluated in 50
      patients with breast cancer and in 15 controls. The expression of these antigens
      in tissue was poorly correlated with the common prognostic parameters. Their
      presence in serum was associated with an altered distribution of the antigens in
      the cell. The expression of these antigens in tissue enables us to select
      patients for serological follow-up and to evaluate tumor differentiation from a
      functional point of view.

PMID- 7829894
TI  - Human meningioma and neuron-specific enolase expression.

PMID- 7829895
TI  - No need to heat bronchoalveolar lavage fluid for calcitonin measurement.

PMID- 7829896
TI  - Unusually high plasma CEA values in a patient with idiopathic pulmonary fibrosis.

PMID- 7829897
TI  - [Principles and methods of influenza epidemiology: with special reference to
      field evaluation of vaccine efficacy].
AB  - In Western countries, prevention of influenza has been a major public health
      concern, promoting the vaccination program to high-risk individuals including the
      elderly. On the other hand, in Japan, there has been no systematic approach to
      such a selective vaccination on the social basis. This is due to the deep-rooted
      skepticism on vaccine efficacy. A number of epidemiologic studies have so far
      reported conflicting results in this country. We investigated the principles and
      methods of influenza epidemiology focusing on the field evaluation of vaccine
      efficacy. General and methodologic problems in vaccine field trials with
      naturally occurring influenza include; unpredictability of the time of its
      occurrence; antigenic differences between the vaccine strains and epidemic
      viruses; preexistence of already-immune individuals; indirect effect of hard
      immunity by vaccination on nonvaccinees; possible difference in the virus
      exposure between compared groups, particularly when epidemic scale is small;
      possible misdiagnosis of cases, if not laboratory-confirmed. To cope with these,
      the following measures are essential in conducting epidemiologic study on
      influenza. 1) Influenza epidemics show differential occurrence by time and place.
      Therefore, much attention should be pain when analyzing the pooled data obtained
      from various study samples at different locations. 2) It should be the first step
      of a research to consider whether the outbreak of acute respiratory illnesses
      observed among subjects is caused by influenza virus exposures. 3) In general,
      failings to detect vaccine efficacy are attributable to the dilution of outcome
      with noninfluenzal illnesses; cases defined by clinical symptoms include
      substantial number of acute respiratory illnesses other than influenza. To
      minimize this nondifferential misclassification, three methods are thought to be
      important; confining observation period during the peak epidemic; applying a
      strict criteria to measure the outcome, preferably with laboratory examination;
      and conducting the study in the season with large-scale epidemic. 4) It is also
      important to take into account the preexistence of already-immune individuals.
      "Antibody efficacy" is a keen index to assess vaccine effectiveness in this
      instance. Besides, further research is required to clarify the individual
      characteristics related to influenza attack, which affect the validity of
      analytic epidemiologic study on vaccine efficacy by yielding bias or confounding
      effect.

PMID- 7829898
TI  - [Inhibition of biofilm formation by clarithromycin (CAM) in an experimental model
      of complicated bladder infection--in vitro study using automated simulation of
      urinary antimicrobial concentration].
AB  - The role of clarithromycin (CAM) in biofilm formation has recently been reported.
      Inhibition of the production or promotion of the dissolution of the glycocalyx, a
      major component of biofilm, has been implicated in its mechanism of action.
      However, the details remain unclear. We used an experimental model of complicated
      urinary bladder infection and automated simulation of the variations in urinary
      antimicrobial concentration to study the efficacy of CMA in inhibiting biofilm
      formation and obtained the following results. 1) Prior to biofilm formation,
      Pseudomonas aeruginosa (P. aeruginosa) was exposed to ciprofloxacin (CPFX, MIC: 8
      micrograms/ml), which was active against the organism, at a dose of 200 mg t.i.d.
      for 7 days. The bacteria were apparently eradicated from the culture medium in
      the experimental model of bladder infection (model bladder) after 32 hours.
      However, when the medium was changed to eliminate the antimicrobial agent on Day
      7, bacterial regrowth was initiated after 4 hours. Scanning electron microscopy
      demonstrated sequential biofilm formation on the surface of glass beads in the
      model bladder diverticulumn, suggesting inside the biofilm were a source of
      regrowth. 2) Prior to biofilm formation, P. aeruginosa was also exposed to CAM
      alone, which has no antimicrobial activity against the organism (MIC: > 128
      micrograms/ml) at a dose of 200 mg t.i.d. for 7 days. In this situation, CAM was
      not active against P. aeruginosa and the bactericidal concentration in the model
      bladder did not decrease markedly, reaching the initial level (10(7) CFU/ml)
      within 48 hours. However, although numerous bacteria were attached to the glass
      beads in the diverticulum, no biofilm was formed. 3) Exposure to a combination of
      CPFX and CAM (each at 200 mg t.i.d. for 7 days) resulted in the eradication of
      bacteria from the model bladder at 32 hours, and no bacterial regrowth was
      demonstrated after the medium was exchanged on Day 7. In addition, no biofilm was
      formed and the bacteria did not become attached to the glass beads. 4) The
      content of alginate, a major component of P. aeruginosa biofilm, was measured per
      5 glass beads on Day 3, 5, and 7 after starting drug administration. The alginate
      content increased with time when CPFX was given alone at a dose of 200 mg
      t.i.d..(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7829899
TI  - Immunoglobulin M and G antibodies in mice in response to Toxoplasma gondii (S
      273) infection and their antigen recognition patterns in western blotting on
      various post-infection days.
AB  - Immunoglobulin M and G antibody responses in mice experimentally infected with
      Toxoplasma gondii (S-273) and the reaction patterns with T. gondii (RH)
      tachyzoite antigens were studied on various post-infection days (PIDs) (2nd to
      36th PIDs) using a commercially available IgM and IgG enzyme linked immunosorbent
      assay (ELISA) test systems and Western blotting (WB) technique. IgM antibody in
      ELISA test appeared to be positive on 12th PID (absorbance 0.764) and reached its
      peak level on 16th PID (absorbance 1.338) showing a slow decline thereafter with
      an absorbance of 0.800 even on 36th PID. Positivity of IgM was confirmed by WB
      except for 36th PID. IgG appeared on 16th PID with an absorbance of 0.248 and
      showed a steady increasing tendency even on 36th PID (absorbance 1.747). However,
      IgG positivity on WB was observed only on 29th PID and afterwards. On Western
      blots, both IgM and IgG showed interesting antigen recognition patterns on
      various PIDs. At the most IgM recognised seven antigens of 14kDa to 53kDa while
      IgG recognised eight antigens of 17kDa to 53kDa. Major antigens recognised by IgM
      were of 53kDa and 21kDa while the major band recognised by IgG was of 19kDa. The
      major bands, however, showed variability in their consistency during various
      PIDs. All the antigens recognised by IgM and IgG were not identical.

PMID- 7829900
TI  - Evaluation of pertussis treatment with erythromycin ethylsuccinate and stearate
      according to age.
AB  - Although erythromycin estolate has been fully assessed for pertussis treatment,
      the evaluation of erythromycin ethylsuccinate and stearate, the main erythromycin
      preparations used in Japan and the US, is inadequate. We evaluated these
      preparations to establish an appropriate treatment for pertussis according to
      age. Sixty-six patients with culture-confirmed pertussis were treated with
      erythromycin administered at a dosage of 40-50 mg/kg/day (maximum, 1.2 g/day).
      Negative culture was obtained in 39% (15/38) of patients aged 0-2 years within
      one week and in 71% (27/38) within two weeks, in 78% (7/9) of those aged 3-15
      years within one week and in 100% (9/9) within two weeks. All 12 adult patients
      had a negative culture within one week. The efficacy of erythromycin for the
      eradication of B. pertussis was significantly lower in children aged 0-2 years
      than in older children. In conclusion, it is desirable to administer erythromycin
      for three weeks to children aged 0-2 years, two weeks to those aged 3-15 years
      and one week to adults.

PMID- 7829901
TI  - [Molecular cloning of alpha antigen like protein gene of Mycobacterium leprae and
      its over production in Escherichia coli].
AB  - I have constructed the genomic library of M. leprae Thai 53 strain, and cloned
      the alpha antigen like protein gene by plaque hybridization method by using M.
      leprae alpha antigen DNA fragment as probe which was characterized in the
      previous study, I have termed it as alpha 2 antigen gene. The alpha 2 antigen
      gene has been characterized by sequencing. By comparing the deduced amino acid
      sequence of alpha and alpha 2 antigen with 85 complex antigen of other
      mycobacteria. I have found the higher homology between alpha 2 antigen and 85A
      antigen and between alpha antigen and 85B antigen. We have constructed the over
      expression system of M. leprae alpha and alpha 2 antigen gene in E. coli using
      vector pMALc-RI. Recombinant alpha and alpha 2 antigen has been purified by
      amylose column chromatography at the purity of more than 95%. More than 6 mg and
      more than 10 mg of recombinant alpha and alpha 2 antigen has been obtained from
      200 ml of liquid culture, respectively. ELISA tests have been performed with the
      sera of leprosy patient and healthy control against the recombinant alpha and
      alpha 2 antigens. The antibody titers in sera of leprosy patient against the two
      kinds of antigens were all much higher than healthy controls. The antibody titer
      against the alpha 2 antigen was higher than that against alpha antigen.
      Recombinant alpha and alpha 2 antigens in this study could be used as a new
      specific antigen for serodiagnosis of leprosy.

PMID- 7829902
TI  - [An epidemiological study of penicillin-resistant Streptococcus pneumoniae in
      Japan].
AB  - In order to investigate penicillin resistance (Pcr) in Streptococcus pneumoniae
      from clinical sources in Japan, a total 1,127 strains of S. pneumoniae was
      collected at random from 36 institutions participating to "Working group for Pcr
      S. pneumoniae" around the country in 1993-1994. These strains were isolated more
      frequently from sputum (38.2%), throat (31.4%), nasal discharge (16.4%), and
      otorrhea (5.7%). A small number of isolates from blood (19 strains; 1.8%),
      cerebrospinal fluid (11 strains; 1.0%), and pleural fluid (2 strains; 0.2%) were
      included respectively. Patients from whom S. pneumoniae was isolated have mostly
      been associated with children < or = 12 years of age and adults 60 < or = years
      olds. These isolates were tested for susceptibility to penicillin G, ampicillin,
      oxacillin, cefixime, cefdinir, imipenem, panipenem, erythromycin, clindamycin,
      minocycline, and vancomycin by an agar dilution method using Mueller Hinton agar
      supplemented with 10% sheep blood. Strains with the MICs > or = 0.125
      micrograms/ml for penicillin G were defined as a Pc resistance. Of the 1,127
      strains, 471 strains (41.8%) were identified as a Pc resistance. Pcr S.
      pneumoniae were almost resistant to other beta-lactams, including ampicillin,
      oxacillin, ceftizoxime, cefixime, cefdinir. Although, the MICs of imipenem and
      panipenem ragned from 0.004-2.0 micrograms/ml with 2 peaks distributions, these
      antibiotics inhibited the growth of most of Pcr S. pneumoniae at the lowest
      concentrations of < or = 0.5 microgram/ml. Only vancomycin resistant strain was
      not detected in these isolates. Most of the Pcr strains were simultaneously
      resistant to macrolides and minocycline. Further more, isolation frequencies of
      Pcr S. pneumoniae in west Japan, were relatively high compared with those of east
      Japan.

PMID- 7829903
TI  - [Tetracycline-resistant plasmid of Salmonella enteritidis isolated in Kumamoto
      City].
AB  - We isolated Salmonella choleraesuis subsp. choleraesuis serovar. Enteritidis (S.
      Enteritidis) from a mass of cases which broke out in September, 1991 in Kumamoto
      City. The isolates were shown to hold plasmids on which a tetracycline (TC)
      resistant gene was located. The plasmid, about 9 kb in size, was capable of
      expressing the gene in Escherichia coli, unstable in S. Enteritidis and
      Escherichia coli. Thus in order to investigate the creeping prevalence of the TC
      resistant plasmid in Kumamoto City and its spreading in other areas, the strains,
      a total of 41, including 37 isolates from sporadic cases with diarrhea in
      Kumamoto City, 3 isolates from 3 cases of food poisoning in Kitakyushu, Fukuoka
      and Chiba, and one strain isolated from egg solution in Kumamoto City, were
      examined by the hybridization test with this plasmid as a probe, as well as for
      their drug sensitivity and plasmid profile. As a result, 28 strains of 37 tested
      from the sporadic cases, the strains from food poisoning in Kitakyushu, Chiba and
      the one from egg solution, all harbored the same 9 kb TC-resistant plasmid. From
      the above observations, it was assured that, at the time of investigation, July
      to September in 1992, the prevalence of S. Enteritidis in Kumamoto City was
      Predominated by its strain carrying the TC-resistant plasmid. Furthermore,
      considering the fact that the strain harboring this plasmid was also found in the
      food poisoning in Kitakyushu and Chiba, it was suggested that spreading of this
      strain was not restricted to localities and was also associated with Chicken eggs
      according to its detection from the egg solution.

PMID- 7829904
TI  - [Studies on respiratory infections in primary care clinic (V). The pattern of
      distribution on bacteria, Mycoplasma pneumoniae and virus isolated from patients
      with respiratory infections, who were seen in six private clinics, and clinical
      efficacy of ciprofloxacin and roxithromycin].
AB  - The pattern of distribution of bacteria, Mycoplasma pneumoniae and virus isolated
      from the same specimen recovered from the throat swab or the sputum of 479
      patients with respiratory infections who were seen in six private clinics in
      Sendai City of Japan during the period from October to November in 1992 (period
      I) and from January to February in 1993 (period II) was documented. Of the 479
      patients, 234 had acute pharyngitis, 145 had acute bronchitis, 96 had influenza,
      21 had acute tonsillitis, 5 had acute pneumonia and 9 had other respiratory
      infections. One hundred (42.4%) strains of potential pathogen and one strain of
      M. pneumoniae were recovered from 236 cases in period I, and 66 (27.2%) strains
      of potential pathogen, one strain of M. pneumonae and 73 strains of Influenza
      virus (30.0%: 43 of type A Hong-Kong and 30 of type B) from 243 cases in period
      II. Of the 166 strains, major isolates were Staphylococcus aureus (56 strains),
      Streptococcus pneumoniae (12 strains), Streptococcus pyogenes (15 strains),
      Haemophilus influenzae (17 strains), Esherichia coli (4 strains), Klebsiella spp.
      (35 strains), Pseudomonas aeruginosa (4 strains) and Acinetobacter spp. (23
      strains). Only one strain of S. aureus was resistant to methicillin (MIC: 50
      micrograms/ml). None of S. pneumoniae was resistant to 1 microgram/ml of
      ampicillin. Ciprofloxacin was administered to 113 cases and roxythromycin to 220
      cases by doctors in charge.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7829905
TI  - [Study of neutrophil dysfunctions in the elderly using a chemiluminescence
      method].
AB  - To evaluate the cause of the vulnerability to infections in the elderly, the
      ability of neutrophil to generate reactive oxygen species was assessed by a
      luminol-dependent chemiluminescence (CL) assay after stimulation with non
      opsonized zymosan, Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella
      pneumoniae, Candida albicans and lumispheres in elderly patients aged 70 to 93
      years. The integrated CL for 20 minutes of whole blood and neutrophils induced by
      zymosan in the elderly was significantly lower than that in healthy young adults,
      and the integrated CL of neutrophils induced by lumispheres was also
      significantly lower in the elderly aged 80 years and over. When bacterial
      infection occurred in the elderly, the levels of CL were elevated and decreased
      in the convalescence. This response is proper for host-defense mechanism against
      infection. However, whole blood CL response was not fully activated in any
      patients of the elderly during bacterial infection. In these cases lower white
      blood cell counts, lower neutrophil counts, or the decreased level of the serum
      total protein, albumin, total cholesterol or cholinesterase were observed.
      Relationship between malnutrition and the ability of neutrophil to generate
      reactive oxygen species was suggested. Furthermore, I evaluated the priming
      effect of lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF-alpha) on
      whole blood CL. The CL responses stimulated with non-opsonized zymosan or P.
      aeruginosa were enhanced by pretreatment with TNF-alpha and LPS in healthy young
      adults. On the other hand, no significant priming effect was observed when blood
      from elderly patients were incubated with each primer. These findings suggest
      that the impairment in the generation of reactive oxygen species of the
      neutrophils and the decrease in reactivity to LPS and TNF-alpha that activate
      neutrophils at the site of infection and potentiate host defense against invading
      bacteria, may contribute to susceptibility to infection in the elderly.

PMID- 7829906
TI  - [Detection of Mycoplasma genitalium from male patients with non-gonococcal
      urethritis by polymerase chain reaction].
AB  - Mycoplasma genitalium causes urethritis in non-human primates, but studies on its
      pathogenicity in man have been hampered by the difficulty in isolating this
      oragnism in culture. We have used a specific polymerase chain reaction to examine
      the role of M. genitalium in non-gonococcal urethritis (NGU). Oligonucleotide
      primers were used to amplify a 281 bp of 140-KDa adhesin gene of M. genitalium. A
      characteristic PCR product was amplified, when M. genitalium DNA was template for
      the PCR. No amplified product was detected in Mycoplasma pneumoniae DNA,
      Mycoplasma hominis DNA or other bacterial DNAs. M. genitalium DNA was detected in
      urethral swabs from 17 (14.9%) of 114 men with NGU. Three (9.1%) of the 33 men
      with Chlamydia-positive NGU and 14 (17.3%) of the 81 with Chlamydia-negative NGU
      were positive for M. genitalium DNA, but 29 men without urethritis were negative.
      The prevalence of M. genitalium in NGU and in Chlamydia-negative NGU was
      significantly higher than that in the normal control. These findings suggest that
      M. genitalium would be a cause of NGU.

PMID- 7829907
TI  - [Studies on local immune response in mouse model of experimental Escherichia coli
      intrauterine infections].
AB  - Studies were conducted to elucidate the immune cell response at infection sites
      by performing immunostaining of immune cells with a monoclonal antibody in an
      experimental Escherichia coli (E. coli) mouse uterine infection model. 1. The
      incidence of uterine infection by E. coli decreased with the passage of time: 4/4
      on Day 1, 4/6 on Day 3, 2/6 on Day 7, and 1/6 on each of Days 14 and 21. It was
      surmised that clearance of the bacteria from the infection sites was being
      carried out by immune cells. 2. Beginning from infection Day 1, the infected
      uterine tissue was observed to undergo a moderate degree of invasion by
      neutrophils, macrophages, CD4+ T cells, CD8+ T cells and IgA+ B cells. Then,
      beginning from infection Day 3, there was a mild degree of invasion of the
      infected uterine tissue by IgM+ B cells and IgG+ B cells. The number of
      neutrophils in the tissue decreased beginning from infection Day 14, but the
      degree of invasion of the infected tissue by the other kinds of immune cells
      remained almost constant through infection Day 21. 3. A comparison was made of
      the immune responses to local infection by E. coli, and Chlamydia trachomatis (C.
      trachomatis), an intracellular parasite. It was found that the invasion of the
      infection site by immune cells occurred earlier in the case of E. coli infection
      than C. trachomatis infection. In addition, the C. trachomatis infection site was
      observed to contain greater numbers of macrophages and CD8+ T cells play
      important roles in the immune defense at sites of infection by C. trachomatis.

PMID- 7829908
TI  - [Basic and clinical studies of fleroxacin on infectious enteritis. Research Group
      of AM-833 on infectious enteritis].
AB  - A clinical study was conducted on fleroxacin (FLRX) in 143 patients and carriers
      with infectious enteritis (shigellosis, Salmonella enteritis, Campylobacter
      enteritis, pathogenic Escherichia coli enteritis, Vibrio parahaemolyticus
      enteritis, cholera, multiple bacterial infections, pathogen-negative enteritis).
      Furthermore, its antibacterial activity against clinical isolates, fecal
      concentration and effect on fecal microflora were conducted. FLRX was
      administered orally in doses of 200 mg once a day (200 mg group) or 300 mg once a
      day (300 mg group) for 3 days to cholera, for 7 days to Salmonella enteritis and
      for 5 days to the other infectious enteritis. The clinical efficacy rates were
      100% in both the 200 mg and 300 mg groups. The bacteriological efficacy rates
      were 100% against Shigella spp., Salmonella spp., pathogenic E. coli, V.
      parahaemolyticus and V. cholerae O1, and 63.6% against Campylobacter spp. in the
      200 mg group. The rates of the 300 mg group were 93.3% against Shigella spp., and
      100% against Campylobacter spp. and pathogenic E. coli. As adverse effects, skin
      rash was observed in 1 case each in both groups (1.1%, 2.1%). Abnormal laboratory
      findings consisted of 1 case of increased eosinophils and 1 case of elevated GOT
      and GPT levels in the 200 mg group (2.8%), and 1 case of elevated GPT in the 300
      mg group (2.9%). The clinical usefulness rates were 92.9% and 93.3% in the 200 mg
      and 300 mg groups, respectively. Antibacterial activity was somewhat inferior to
      that fo ciprofloxacin and equal to or better than that of norfloxacin,
      demonstrating MIC90 values against Shigella spp., Salmonella spp., pathogenic E.
      coli, V. parahaemolyticus and Campylobacter spp. of 0.1, 0.2, 0.1, 0.2 and 0.78
      micrograms/ml, respectively. Peak fecal concentrations of the drug were 49.0
      micrograms/g and 274.4 micrograms/g in the 200 mg group, and 43.3 micrograms/g
      and below the detection limit (5.0 micrograms/g) in the 300 mg group. With
      respect to fecal microflora (4 cases), a decrease in Enterobacteriaceae was
      observed in 3 cases during dosing. But this change showed a tendency to recover
      after completion of dosing. No effects were observed on anaerobic bacteria.

PMID- 7829909
TI  - [In vitro antibacterial activity of fleroxacin (FLRX) against clinical isolates
      from bacterial enteritis].
AB  - Antibacterial activity of fleroxacin (FLRX), a new quinolone antimicrobial,
      against 36 strains of Shigella app., 14 strains of Salmonella spp., 11 strains of
      Escherichia coli, 9 strains of Vibrio spp. (including 2 strains of V. cholerae
      O1), 14 strains of Campylobacter jejuni/coli, 3 strains of Aeromonas spp. and 1
      strain of Plesiomonas shigelloides isolated from infectious enteritis patients in
      this study was determined. Its activity was compared with that of ciprofloxacin
      (CPFX), norfloxacin (NFLX) and nalidixic acid (NA). The MIC90 values of FLRX were
      0.1 microgram/ml against Shigella spp. and E. coli, 0.2 microgram/ml against
      Salmonella spp. and Vibrio spp., and 12.5 micrograms/ml against C. jejuni/coli
      MIC90 of FLRX was comparable to that of CPFX and NFLX against Vibrio spp..
      Against other species, MIC90 of FLRX were 2- to 4-fold higher than those of CPFX,
      whereas equal to or 2-fold lower than NFLX. FLRX demonstrated excellent activity
      against an NA-resistant (MIC: > 100 micrograms/ml) isolate of E. coli, with MIC
      0.78 microgram/ml. FLRX showed 8-fold higher activity than NA against other
      strains. The antibacterial activity of FLRX was compared with that of NA against
      stocked strains (clinical isolates from August 1989 to February 1991), consisting
      of 11 strains of Shigella spp., 10 strains of Salmonella spp., 8 strains of E.
      coli, 10 strains of V. cholerae O1, 10 strains of V. parahaemolyticus and 14
      strains of C. jejuni/coli. MICs of FLRX were 0.78 and 12.5-25 micrograms/ml
      against Shigella spp. and C. jejuni/coli that showed resistance of NA (MIC: > or
      = 100 micrograms/ml), respectively. Based on the above, although the absolute
      MICs are low against E. coli and shigella spp., a value of 0.78 micrograms/ml for
      FLRX suggested that such strains should be considered to be resistant.

PMID- 7829910
TI  - [A case report: cryptococcal meningitis and fluconazole therapy].
AB  - An 18-year-old female was given prednisolone and azathioprine for treatment of
      systemic lups erythematosus. She was admitted to Fukuoka University Hospital
      because of headache and vomiting. Examinations revealed she was suffering from
      cryptococcal meningitis. Fluconazole (FLCZ) 400 mg a day was administrated for
      therapy. Her general condition improved and the serum level of cryptococcal
      antigen decreased one month after therapy. This therapy resulted in abatement of
      subjected symptoms and sterilization of the cerebral spinal fluid. This case
      suggested that therapy with FLCZ alone is useful for patients with cryptococcal
      meningitis, therefore the standard therapy with amphotericin B (AMPH) or the
      combination.

PMID- 7829911
TI  - [A case of TSS complicated with SSSS in an adult with liver cirrhosis].
AB  - This paper reports a case of TSS complicated with SSSS in an adult with liver
      cirrhosis. A 52-year-old male, heavy drinker, was referred to our clinic
      complaining lumbago and painful swelling of the right arm. The patient had
      peeling of the skin over the hips, knees and elbows with positive Nikolsky's
      sign. The patient was in a state of shock on admission. Pyrexia persisted for 4
      days and finally the body temperature rose up to 39 degrees C. The laboratory
      studies revealed hypoxia, DIC and multiple organ failure, and these became
      progressively worse. He died 4 days after admission. According to the criteria,
      he was diagnosed as TSS, and TSST-1 was detected from his serum. Staphylococcus
      aureus, coagulase type V was cultured both from the blood and from the wound of
      his right middle finger. This isolated strain did not produce TSST-1. The skin
      specimen at autopsy showed that the cleavage plane lied at the subcorneal region
      and close to the granular layer, with specific changes caused by exfoliative
      toxin. It was compatible to the exfoliation which was caused by exfoliative toxin
      produced from the S. aureus coagulase type V. The autopsy also revealed alcohol
      liver injury, liver cirrhosis and multiple organ failure due to shock state. SSSS
      is rare in adults, to our knowledge this is the first reported case of TTS
      complicated with SSSS.

PMID- 7829912
TI  - [Fulmonant group A streptococcal infection accompanied by massive pulmonary
      hemorrhage and subsequent asphyxia: a case report].
AB  - A case of fulminant group A streptococcal infection occurring in a 6-year-old
      Japanese child is reported. She was accompanied by massive pulmonary hemorrhage
      and subsequent asphyxia. She initially had pharyngalgia with fever. The
      cephalosporin antibiotic was given orally for 3 days. Three days after that
      recurrence of fever and pharyngalgia was noted. Twelve hours later tachypnea and
      a sudden onset of hemoptysis was noted. She manifested DOA (dead on arrival) and
      died in the emergency room. Autopsy revealed the presence of numerous cocci in
      the vessels and massive pulmonary hemorrhage. Streptococcus pyogenes was isolated
      from the blood. The serotype of this group A streptococcal organism was typed as
      M4, T4, which produces exotoxin type B and C, which was sensitive to the
      penicillins.

PMID- 7829913
TI  - [A case of severe tsutsugamushi disease without eruption].
AB  - A 64-year-old male was admitted to our division because of fever. After
      admission, the patient was given beta-lactam antibiotics intravenously because he
      had no eruption and eschar. However, the fever continued, and he became
      unconsciousness and DIC appeared. We diagnosed the patient as Tsutsugamushi
      disease from indirect fluorescent antibody technique. Minocycline was excellently
      effective. Several reports of Tsutsugamushi disease without eruption have been
      given, so we must always be careful of Tsutsugamushi disease.

PMID- 7829914
TI  - [Properties of verocytotoxin-producing Escherichia coli of bovine origin in
      Japan].

PMID- 7829915
TI  - Neurotoxins: a neuroscience nursing challenge.
AB  - Societal awareness of toxins in general has been heightened in the past few
      decades with the increased focus on environmental concerns. The medical
      profession has been aware of the effects of some toxins such as lead and mercury
      for centuries, while other toxins have more recently been identified.
      Neuroscience nurses are challenged to be aware of the neurological effects of
      lesser known toxins, such as ciguatera and methyl bromide, and to meet the
      complex needs of patients who are suffering from the effects of toxic levels of
      these substances.

PMID- 7829916
TI  - Ventriculoperitoneal shunt dysfunction and constipation: a chart review.
AB  - Children treated for hydrocephalus frequently experience chronic constipation. A
      retrospective chart review was conducted to determine if there is a population of
      children with ventriculoperitoneal (VP) shunt dysfunction in whom constipation
      might be a factor in the shunt dysfunction. Of 51 cases reviewed, 19 had
      documented constipation, such as no bowel movement for 2 or more days, small hard
      ball-like stools or fullness of the colon noted on physical examination or
      abdominal radiographs. In 6 cases, a bowel cleansing was performed and signs and
      symptoms of shunt dysfunction resolved without shunt revision. This review
      suggests that constipation may affect the fluid or pressure dynamics of the VP
      shunt and contribute to shunt dysfunction.

PMID- 7829917
TI  - Cerebral hemodynamics: monitoring arteriojugular oxygen content differences.
AB  - Arteriojugular oxygen difference (AJDO2) is used to manage the care of acute head
      injured patients by monitoring the relationship between cerebral metabolism and
      blood flow. Blood samples from the jugular bulb and a peripheral artery are
      monitored either continuously or episodically to calculate AJDO2 and cerebral
      oxygen utilization. An understanding of cerebral oxygen transport physiology is
      essential to measuring AJDO2. A case study highlights the use of AJDO2
      monitoring.

PMID- 7829918
TI  - Development and preliminary testing of the neurological assessment instrument.
AB  - The purpose of this study was to test a neurological assessment instrument (NAI),
      used to assess neurological function in adults with acute brain lesions.
      Instrument items were designed to reflect different aspects of neurological
      function and assess consciousness along the arousal/awareness continuum as
      described by Plum and Posner. Content of the NAI was validated by 10 neuroscience
      expert physicians, nurses and speech pathologists. Reliability was tested with
      one pair of raters on 39 neurologically stable patients with acute brain lesions.
      Based on preliminary findings, the critical preliminary steps have been taken
      towards establishing a reliable and valid instrument with the potential of
      improving the assessment of neurological function in patients with acute brain
      lesions.

PMID- 7829919
TI  - Importance of health and family variables related to quality of life in
      individuals with uncontrolled seizures.
AB  - Approximately 2.5 million Americans are epileptic, and nearly 150,000 new cases
      are diagnosed in the United States each year. While seizures are the most common
      physical symptom of epilepsy, treatment must include far more than medical
      intervention for seizure control. Virtually all aspects of life are affected by
      the disorder including personal relationships, employment, perception of self and
      overall quality of life. A literature review indicates that, while progress is
      being made in identifying variables which impact quality of life, little
      consensus exists regarding their nature. No two patients are necessarily alike,
      nor are their methods of dealing with the disorder necessarily the same.
      Arguments have been posed which state that age of onset is a factor, as is the
      degree to which seizures can be controlled. This is not to say, however, that
      effective interventions cannot be developed to assist patients in dealing not
      only with the physical manifestations of epilepsy but other common related
      factors as well. The purpose of this study was to identify those variables which
      impact quality of life for persons with epilepsy, and in light of the findings,
      to make recommendations for nursing interventions.

PMID- 7829920
TI  - Treatment of nonepileptic psychogenic events in adolescent patients using the
      systems model for intervention.
AB  - Nonepileptic psychogenic events in children, adolescents and adults can be
      difficult to treat. Using a systems framework intervention method resulted in
      significant reduction in nonepileptic psychogenic events. This method provides
      for a continuous flow of interaction, feedback and modification among the health
      care team, family and community. Common goals and plans are defined and
      implemented with a mechanism for feedback and modification. Using a systems model
      approach in educating the caregivers resulted in immediate and long-term
      reduction in nonepileptic psychogenic events.

PMID- 7829921
TI  - Psychogenic seizures: a guide for patients and families.

PMID- 7829922
TI  - Nursing implications of the intracarotid amobarbital procedure.
AB  - The intracarotid amobarbital procedure, by inactivation of each hemisphere,
      provides the opportunity to evaluate language and memory function of the
      individual considering epilepsy surgery. Careful explanation of this procedure,
      and its importance to the proposed surgery are vital to the patient's cooperation
      and performance during this examination. The neuroscience nurse has a significant
      role in the success of this procedure. Nursing interventions include patient
      education, monitoring for potential complications, providing comfort measures,
      and assisting in the management of any life-threatening complications which do
      develop. A relatively little-known procedure outside of comprehensive epilepsy
      centers, the IAP offers opportunities for nursing research. These queries include
      investigation of emotional reactions in relation to gender differences, cultural
      and educational factors which may effect stimulus selection (eg, bilingual
      patients) and patient performance.

PMID- 7829923
TI  - [Regulatory mechanisms for liver-selective transcription of ornithine cycle
      enzyme genes].

PMID- 7829924
TI  - [Ca2+/calmodulin-dependent protein kinase II: structure and function].

PMID- 7829925
TI  - [Triplet repeat expansion associated with genetic diseases].

PMID- 7829926
TI  - [Specialized roles of mitochondria and peroxisomes in fatty acid oxidation].

PMID- 7829927
TI  - [Maf nuclear oncoprotein family members as transcriptional regulators].

PMID- 7829928
TI  - [Heterogeneity of Ras GTPase-activating proteins].

PMID- 7829929
TI  - [Acetyl-CoA pathway--CO2 fixation in anaerobic bacteria].

PMID- 7829930
TI  - [A novel fluorochrome for in situ hybridization].

PMID- 7829931
TI  - A clinical decision support system prototype for cardiovascular intensive care.

PMID- 7829932
TI  - Postoperative information transfer: a study comparing two university hospitals.
AB  - Several studies have addressed the processing of anesthetic information by paper
      anesthetic data records or by the electronic storage and transfer of anesthetic
      data. Our purpose was to analyze the oral transfer of information in the
      postoperative period. We investigated 198 post-operative transfer situations with
      120 patients in a U.S. hospital to compare the results with those of a former
      study in a German hospital. A great number of parameters were used in both
      hospitals, but there were remarkable differences. In the U.S. hospital numeric
      values of current vital functions, including oxygen saturation, were more common
      during information transfer, whereas in the German hospital the emphasis was on
      case history and chronic health status. The data from the U.S. hospital and those
      of the German hospital show that in spite of complete anesthetic records, a short
      (112.3 +/- 104 sec in the U.S. and 94.1 +/- 83.6 sec in Germany) oral information
      transfer is inevitable when the patient is transferred from the OR to the
      recovery room, and from the recovery room to the ward (122.7 +/- 61.4 sec in the
      U.S. and and 88.0 +/- 73.0 in Germany). Software developers of patient data
      management systems could learn from this study that in some situations it is
      necessary and possible to create a small set of data which will reflect the
      patients status quite well.

PMID- 7829933
TI  - Presentation and evaluation of a new optical sensor for respiratory rate
      monitoring.
AB  - A new optical sensor for respiratory rate monitoring was simultaneously compared
      with an acoustic sensor and a transthoracic impedance plethysmograph during
      normoventilation in the respiratory rate range of 9-17 breaths per minute. The
      response characteristics of the optical sensor were then measured during
      simulation of central apnoea and tachypnoea. Visual observation was chosen as the
      reference method for monitoring the respiratory rate. The measurements were
      performed in ten healthy volunteers and the respiratory signals recorded on an
      analogue tape and strip-chart recorder and analysed off-line. The response
      characteristics of the fibre optic sensor corresponded well with those of the
      acoustic sensor and impedance plethysmograph. All three methods responded rapidly
      to an apnoeic event.

PMID- 7829934
TI  - A clinical decision support system prototype for cardiovascular intensive care.
AB  - This paper describes the development and validation of a decision-support system
      prototype that can help manage hypovolemic hypotension in the Cardiovascular
      Intensive Care Unit (CVICU). The prototype uses physiologic pattern-matching,
      therapeutic protocols, computational drug-dosage response modeling and expert
      reasoning heuristics in its selection of intervention strategies and choices. As
      part of model testing, the prototype simulated real-time operation by processing
      historical physiologic and intervention data on a patient sequentially,
      generating alerts on questionable data, critiques of interventions instituted and
      recommendations on preferred interventions. Bench-testing with 399 interventions
      from 13 historical cases showed therapies for bleeding and fluid replacement
      proposed by the prototype were significantly more consistent (p < 0.0001) than
      those instituted by the staff when compared against expert critiques (80% versus
      44%). This study has demonstrated the feasibility of formalizing hemodynamic
      management of CVICU patients in a manner that may be implemented and evaluated in
      a clinical setting.

PMID- 7829935
TI  - Is proximal airway pressure a good reflection of peripheral airspace pressure in
      infants and children models under HFJV?
AB  - This experimental study was carried out to determine if an alveolar positive end
      expiratory pressure (PEEP) could occur during high frequency jet ventilation
      (HFJV) in infants, and if tracheal pressure is a good estimation of alveolar
      pressure. We used physical models simulating a 1.5 kg premature (P), a 3 kg
      newborn (N) and a 6 kg child (C) with normal compliance and normal resistance.
      Moreover, in the N model, we used two different resistances and lung compliance
      heterogeneity was studied in the P model. Pressure was measured simultaneously in
      the tube simulating trachea (Paw) and in the bottle simulating the lung (Palv).
      HFJV was performed either via an endotracheal tube (ETT) or via a long catheter
      as in laryngoscopy. The ratio of injection time upon cycle duration (Ti/Ttot) was
      20% or 30%, jet frequency was altered from 150 to 300 min-1 and the driving
      pressure was set as in clinical practice (0.5 and 0.6 bar). PEEP occurred mainly
      in N (1.1 to 3.2 cm H2O) and C models (0 to 3.5 cm H2O). It was inversely related
      to expiratory time (Te). The end-expiratory pressure drop between Palv and Paw
      (delta EEP) was higher in N and increased from 0.5 to 2 cm H2O with the
      shortening of Te and with airway resistances, i.e. the presence of ETT. In the
      heterogeneous model, PEEP and delta EEP were greater in the higher compliance
      alveolus. This study shows that the end-expiratory Palv is underestimated by end
      expiratory Paw.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7829936
TI  - Differences in the topographical distribution of EEG activity during surgical
      anaesthesia and on emergence from volatile anesthetics.
AB  - Computerized processing of a 16 channel EEG allows mapping and display of
      cortical electrical activity in a useful mode for intraoperative monitoring. We
      studied the topographical distribution of EEG-activity displayed as spectral maps
      comparing inhalational anaesthesia with isoflurane or enflurane during surgical
      anaesthesia and emergence. Two groups of nine patients each were anaesthetized
      with one of the two regimens. The EEG patterns during steady state end-tidal
      concentrations of isoflurane (0.7-1.1%) or enflurane (0.8-1.3%) showed highest
      activity in the frontal and occipital areas. At near awakening the frontal and
      occipital dominance of delta activity disappeared in both groups and was replaced
      by homogeneous delta activity over the entire cortex; variations in the
      topographical distribution of enflurane and isoflurane were recorded in the other
      spectral bands. We conclude that changes in topographic EEG patterns observed
      during the transition from surgical anaesthesia to emergence, in particular the
      disappearance of frontal and occipital dominance of delta activity common to
      isoflurane and enflurane, may serve to detect undesirably light levels of
      anaesthesia.

PMID- 7829937
TI  - Assessment of depth of general anesthesia. Observations on processed EEG and
      spectral edge frequency.
AB  - The daily use of muscle relaxants and the lack of correlation between the
      hemodynamic behavior and stages of general anesthesia represent the main
      obstacles in defining the level of cortical activity depression by the anesthetic
      drugs. Since classical EEG is cumbersome in the operating room, and demands
      special knowledge, computerized methods of EEG wave analysis have more or less
      replaced the 'raw' display of the electrical activity of CNS. The paper describes
      the place of spectral edge frequency (SEF), one of the parameters obtained by
      processing the EEG waves, in the list of variables which could be monitored
      during general anesthesia. Besides, our preliminary observations on a combination
      of mean blood pressure variations and SEF value are presented. In fact, we
      designed a hypothetical matrix of those two parameters, which seems to be a
      useful tool for guiding the general anesthesia. SEF kept in a pre-established
      range (usually 8-12 Hz) seems to be linked with a more evident hemo-dynamic
      stability. Some data also suggested that a stable SEF on that range contributed
      to a higher degree of immediate postoperative analgesia after Cesarean section.
      The limits of SEF oblige the scientists to go on looking for other monitored
      parameters, to be studied in correlation with processed EEG. Further studies are
      needed, in order to improve the anesthesiologist's capabilities to define
      correctly the stage of general anesthesia.

PMID- 7829938
TI  - Kikuchi-Fujimoto disease: a report of two cases and an overview.
AB  - Kikuchi-Fujimoto disease (KFD) has been widely reported from Japan and
      sporadically from many parts of the world including Saudi Arabia, since its
      original description in 1972 but the disease remains poorly known by clinicians.
      In this paper we report two Saudi patients seen in Tabuk, Saudi Arabia. One was a
      36-year-old Saudi man and the other a 16-year-old Saudi girl. Both presented with
      cervical lymphadenopathy and pyrexia. Histological examination of biopsy material
      from both showed classical features of KFD. Other laboratory findings were
      unremarkable except for leucopenia. Following excision biopsy both patients
      recovered without sequelae. KFD is a self-limiting process of uncertain aetiology
      that predominantly affects young women aged 20-30 years. We review the pathology,
      clinical featuers and possible aetiology of this interesting disease, which may
      well be underdiagnosed. Increased awareness of KFD will minimize the risk of
      confusing this entity with malignant lymphoma or other serious conditions.

PMID- 7829939
TI  - Kimura's disease: case report and brief review of the literature.
AB  - Kimura's disease is a chronic inflammatory disease which often presents as a
      tumour-like swelling in the head and neck region with or without lymphadenopathy.
      Most cases have been described predominantly in Chinese and Japanese people. The
      lesion is benign, but it may easily be mistaken for a malignant tumour. Kimura's
      disease has been confused with angiolymphoid hyperplasia with eosinophilia
      (ALHE), from which it probably should be distinguished as a separate entity. The
      diagnosis may be suggested by a fine needle aspirate, but is established by a
      biopsy. The treatment of choice is surgical removal. A case of Kimura's disease
      in a Caucasian male of 12 years' duration is presented together with a brief
      review of the literature.

PMID- 7829940
TI  - Localized mastoiditis simulating a facial nerve schwannoma on MRI.
AB  - A case of a single inflamed mastoid air cell is described. This was initially
      interpreted as a facial nerve schwannoma on MRI examination. Careful evaluation
      of the signal characteristics and additional findings from the high resolution CT
      examination helped to establish the correct diagnosis.

PMID- 7829941
TI  - Late sino-nasal metastasis from follicular thyroid carcinoma.

PMID- 7829942
TI  - Blast injury of the auditory system: a review of the mechanisms and pathology.
AB  - Blast injury of the auditory system is uncommon and our knowledge incomplete.
      This article reviews the literature to date giving an account of the interactions
      of blast waves with the ear, the mechanisms of injury, the pathology, the
      clinical features, and an outline of management principles.

PMID- 7829943
TI  - The natural history of otitis media with effusion--a three-year study of the
      incidence and prevalence of abnormal tympanograms in four South West Hampshire
      infant and first schools.
AB  - Otitis media with effusion (OME) is both extremely common in young children, and
      variable in its duration and severity. This study aims to gather and consider new
      and reliable information about the incidence and prevalence of OME in British
      school children. Eight hundred and fifty-six school children aged five to eight
      years from four South West Hampshire schools were examined over a three-year
      period by tympanometry, a method used to detect OME (> 90 per cent specificity
      and sensitivity) performed once per school term. Normal ears were recorded in
      54.9 per cent of children throughout with 27 per cent recording evidence of
      effusion. However in only one out of 10 of the affected children did the fluid
      persist for a year or more. This impressive clearance is due in part to natural
      resolution, with the intervention of surgery occurring in about one in eight of
      the children with identified effusions. OME is more common in five-year-olds with
      an annual prevalence of 17 per cent compared to six per cent in eight-year-olds
      and is more common in the winter months. Because of the variability of the
      condition at least two screenings are recommended as a basis for good management.

PMID- 7829944
TI  - Fenestration and occlusion of posterior semicircular canal for patients with
      intractable benign paroxysmal positional vertigo.
AB  - A series of 15 patients with intractable benign paroxysmal positional vertigo
      (BPPV) who had fenestration and occlusion of the posterior semicircular canal
      (FOP) surgery commencing in December 1990 are reported. Follow-up was from 14 to
      40 months. All patients reported a cure of their positional vertigo. No patient
      regretted having the surgery. All patients had a negative Dix-Hallpike test post
      operatively and the test remained negative for the duration of follow-up. Eight
      patients had a mild high frequency sensorineural hearing (SNHL) loss post
      operatively which had almost recovered six months later. No patient reported any
      change in their hearing following surgery. Of the 10 patients who did not have
      pre-operative tinnitus, six developed tinnitus but it was not considered
      significant by them. All patients developed mild unsteadiness following surgery
      which gradually improved with mobilization and physiotherapy if necessary. The
      operation preserves hearing, is technically straightforward, well-tolerated and
      effective.

PMID- 7829945
TI  - The possible contributing factors for the success of steroid therapy in Bell's
      palsy: a clinical and electrophysiological study.
AB  - Incomplete recovery from Bell's palsy was observed in some patients even after
      the intake of corticosteroids. This prospective study was performed on 160
      patients with unilaterial nonrecurrent Bell's palsy in order to investigate the
      role of prednisolone on the prognosis of Bell's palsy. Ninety-three patients were
      given prednisolone tablets (1 mg/kg body wt/day up to 70 mg) for six successive
      days, then the dose was reduced gradually over the next four days. The remaining
      67 patients were not given prednisolone (control group). Facial nerve recovery
      was assessed clinically and electrophysiologically for up to one year. The
      results of this study suggested that the most probable contributing factor for
      the success of prednisolone in improving the prognosis of Bell's palsy was its
      early intake (within the first 24 hours following onset).

PMID- 7829946
TI  - Scleroma of the eustachian tube: salpingoscleroma.
AB  - Rhinoscleroma is a chronic specific granulomatous inflammatory condition that has
      an affinity with the mucosa of the upper respiratory tract. Involvement of the
      eustachian tube is uncommon. In the present study nasopharyngoscopy was performed
      in 20 patients with rhinoscleroma to find out the type, nature and site of the
      lesion at the orifices of the eustachian tube. A lesion involving the eustachian
      tube was found in six cases (30 per cent). Lesions occurred in the form of
      atrophic changes with crusting, granuloma and fibrotic thick areas. Involvement
      of the eustachian tube was found to be associated with intranasal scleroma and
      was more common at the granulomatous stage. Eustachian tube scleroma had a
      possible association with subsequent changes in the tympanogram pattern.
      Nasopharyngoscopy was found to be of therapeutic value in removing the crust,
      discharge and granulations at the eustachian tube orifices.

PMID- 7829947
TI  - Sarcomas of nasal cavity and paranasal sinuses: chondrosarcoma, osteosarcoma and
      fibrosarcoma.
AB  - Forty-two patients were treated for sarcoma of the nasal cavity and paranasal
      sinuses at the Institut Gustave Roussy, Paris, between 1960 and 1993. Twelve
      patients had chondrosarcoma (CS), 14 had osteosarcoma (OS) and 16 had
      fibrosarcoma (FS). Ten patients had grade I, six grade II and 26 grade III
      tumours. All but 10 patients had surgery for the primary tumour. A significantly
      increased risk of local failure was associated with the male sex (p < 0.01),
      grade III tumours (p < 0.02) and patients excluded from surgery (p < 0.04). The
      overall incidence of local and distant failure was 76 and 12 per cent
      respectively. Overall survival was 28 per cent at three years and 23 per cent at
      five years. Eight patients (20 per cent) were alive more than 10 years later. The
      factors significantly influencing survival were sex (p < 0.01), grade (p < 0.05)
      and local failure (p < 0.01).

PMID- 7829948
TI  - Evaluation of upper airway obstruction after partial laryngectomies by
      radiological method and flow-volume loop analysis.
AB  - Anatomical and functional estimations of the upper airways in patients after
      partial laryngectomies (cordectomy, hemilaryngectomy, enlarged hemilaryngectomy)
      carried out due to cancer are discussed in this paper. The post-operative lumen
      of the larynx and the trachea were estimated by radiological examination. The
      coefficient larynx/trachea (L/T) was proposed to describe fixed obstruction. At
      the same time, all patients underwent spirometric examinations. Inspiratory and
      expiratory parameters of the flow-volume loop were evaluated. In 39 patients the
      L/T coefficient was lower than in a group of patients with chronic bronchitis (p
      < 0.05). Also inspiratory and some expiratory parameters of the flow-volume loop
      decreased in contrast to the group with chronic bronchitis. All results showed
      the usefulness of radiological and spirometric methods in detecting upper airway
      obstructions and confirmed their fixed character. The influence of the area of
      operation on the degree of upper airway obstruction was emphasized.

PMID- 7829949
TI  - Expression of the cell-cell adhesion molecule E-cadherin in tongue carcinoma cell
      lines.
AB  - A reduction in cell adhesiveness and cell invasion are essential steps in tumour
      progression. In the present study six tongue carcinoma cell lines were compared
      with regard to their invasive potential in two in vitro invasion assay systems
      and for their patterns of expression of the cell-cell adhesion molecule E
      cadherin. The three cell lines negative for E-cadherin expression were invasive
      in both assays. One cell line with strong E-cadherin expression was strongly
      invasive and one weakly invasive. One cell line with reduced E-cadherin
      expression was weakly invasive. There was no significant pattern to these
      findings (chi 2 = 0.375; p = 0.54). This supports previous studies from this
      group that suggest that E-cadherin is only one of the presumably many molecules
      involved in tumour progression in squamous cell carcinoma of the tongue.

PMID- 7829950
TI  - Microvascular free flaps in head and neck surgery.
AB  - This study is a retrospective review of 60 patients who had microvascular free
      flap reconstructions in the head and neck region. They were all performed over a
      10-year period by a single surgeon. The series includes a wide range of flap
      types and analyses pre-operative risk factors for flap failure as well as
      complications and outcome. Smoking and advanced age did not appear to prejudice
      flap survival but peripheral vascular disease, cardiac disease and alcohol
      withdrawal were found to increase the likelihood of flap failure. The most
      frequent complications encountered were thrombosis of one of the anastomosis and
      haematoma. The most successful flap in terms of survival and function was the
      fasciocutaneous radial forearm flap. The literature is reviewed in relation to
      the general principles of microvascular free flap surgery and the results of this
      series are placed in context.

PMID- 7829951
TI  - Reconstruction of the mandible with conventional bone graft: an evaluation.
AB  - Eighteen patients with bony defects of the mandible had the mandible
      reconstructed using conventional nonvascularized bone grafts from the iliac
      crest. After surgery they received radiotherapy for cancer in the oropharynx or
      oral cavity. This study was carried out over a 10-year period. All patients were
      followed-up both for their tumour growth and the results of their reconstruction.
      Four to 10 years after surgery 55.5 per cent were alive and well. Full dental
      rehabilitation was achieved in 33 percent and 12.5 percent were without dental
      rehabilitation.

PMID- 7829952
TI  - Topical antiseptic mouthwash in oncological surgery of the oral cavity and
      oropharynx.
AB  - A multivariant analysis of the value of the use of a pre-operative topical
      antiseptic mouthwash to reduce the incidence of post-operative wound
      complications in 106 consecutive patients undergoing head and neck surgery
      involving the oral cavity or oropharynx was carried out at the University of
      Iowa, Department of Otolaryngology--Head and Neck Surgery. An oral presentation
      employing povidone-iodine solution was used for 43 patients. The remaining 63
      patients studied received no oral presentation. Unfavourable wound outcome was
      not associated with age, sex, presence and condition of teeth, or serious pre
      existing medical illnesses. A significant correlation was found between post
      operative wound breakdown and type of closure, stage of disease, and previous
      operation or radiotherapy. The use of an oral preparation correlated
      significantly with favourable wound outcome independent of all other variables (p
      < 0.01). Our data support the use of a topical antiseptic mouthwash to reduce the
      incidence of post-operative wound complications in surgery of the oral cavity and
      oropharynx.

PMID- 7829953
TI  - Technique of tracheo-oesophageal puncture under local anaesthesia.
AB  - Various techniques for performing a secondary tracheo-oesophageal puncture to
      enable insertion of a speech prosthesis in laryngectomized patients have been
      described. We describe a modification that allows a safe secondary tracheo
      oesophageal puncture under local anaesthesia using standard equipment available
      in an ENT department.

PMID- 7829954
TI  - Vestibular schwannoma in an only hearing ear.
AB  - A vestibular schwannoma in an only hearing ear is a difficult management problem.
      A case is presented of a patient who had a Nucleus-22 channel device implanted
      into a nonfunctioning ear and auditory rehabilitation prior to resection of a
      large vestibular schwannoma in the contralateral ear.

PMID- 7829955
TI  - False positive MRI in the diagnosis of small intracanalicular vestibular
      schwannomas.
AB  - The current gold standard for diagnosing vestibular schwannomas is MRI with
      gadolinium-DTPA enhancement. This imaging modality is particularly useful in the
      detection of small intracanalicular tumours which can be missed by CT scanning.
      We present a case where MRI with enhancement suggested the presence of a 4 mm
      intracanalicular vestibular schwannoma. Surgical exploration of the internal
      auditory canal via a retrosigmoid approach, revealed no tumour, but inflammatory
      arachnoid matter around the vestibular nerve was found. A review of the
      audiological test results uncovered some results which did not correlate with the
      interpretation of the MRI scan. We would therefore caution against immediate
      surgical intervention in patients where the diagnosis of a small intracanalicular
      vestibular schwannoma is not totally supported by the audiological findings. In
      such cases rescanning with gadolinium enhancement after a suitable interval is
      recommended.

PMID- 7829956
TI  - Large vestibular aqueduct syndrome and stapes fixation.
AB  - An abnormally large vestibular aqueduct has a well recognized association with
      inner ear anomalies and it has been assumed previously to be a variant of a
      Mondini type of deformity (Shuknecht, 1980; Emmett, 1985). The sole radiological
      finding in some patients with progressive sensorineural loss has been a large
      vestibular aqueduct (Valvassori and Clemis, 1978; Valvassori, 1983), which is now
      accepted as a separate clinical entity, i.e. the large vestibular aqueduct
      syndrome (LVAS). A case is presented which is believed to be the first reported
      with unilateral LVAS and stapes fixation and also the first stapes gusher
      described in association with LVAS.

PMID- 7829957
TI  - Unilateral nasal obstruction: an unusual presentation of a complication of
      nasotracheal intubation.
AB  - Partial avulsion of the middle turbinate is an unusual complication of
      nasotracheal intubation while minor nasal mucosal trauma is not uncommon. Nasal
      turbinate avulsion often presents with persistent epistaxis but in the case
      reported, unilateral nasal obstruction with minimal epistaxis was the presenting
      feature. Unilateral nasal obstruction following nasotracheal intubation should
      raise suspicion of significant disruption of the intranasal architecture.

PMID- 7829958
TI  - Fibrosarcoma of the vocal fold: a late complication of radiotherapy.
AB  - The carcinogenic effect of ionizing radiation is a well known phenomenon.
      However, the induction of malignancies following irradiation for head and neck
      cancers is quite rare (Steeves and Vataini, 1982). Most reported cases are
      osteogenic sarcomas with soft tissue sarcomas encountered less often. We report a
      rare case of fibrosarcoma of the larynx, following radiation therapy for glottic
      carcinoma.

PMID- 7829959
TI  - Coexistence of MALT-type lymphoma and squamous cell carcinoma of the larynx.
AB  - A 66-year-old Japanese man was diagnosed as having a MALT-type lymphoma by
      histopathological examination. The lesion involved the vocal folds bilaterally,
      occupying the larynx and extending beyond it, as shown by computed tomography
      (CT). A course of radiation therapy with moderate doses was given. Six months
      later, a squamous cell carcinoma was found in the larynx and total laryngectomy
      was then performed. The patient remained well, without recurrence, 46 months
      after the operation. thus, MALT-type lymphoma may coexist with a squamous cell
      carcinoma of the larynx.

PMID- 7829960
TI  - Solitary fibrous tumour arising from sublingual gland: report of a case.
AB  - A solitary fibrous tumour is a pleural tumour which may rarely be detected at non
      pleural sites. In this report, the case of a solitary fibrous tumour arising from
      the sublingual salivary gland is described.

PMID- 7829961
TI  - Comparative ultrastructure and immunolabeling of MHC-II antigens of alveolar
      macrophages obtained from patients with paracoccidioidomycosis and other lung
      diseases.
AB  - Samples of alveolar macrophages (AM) obtained by bronchoalveolar lavage from
      patients with either paracoccidioidomycosis, silicosis, sarcoidosis, or allergic
      alveolitis were investigated by electron microscopy and immunocytochemistry to
      compare cellular ultrastructure and expression of MHC-II antigens in the AM cell
      surface. All samples of AM obtained from patients with these pathologies showed
      heterogeneous structural features. Although, this morphological diversity is also
      present in AM of healthy donors, our observations seem to indicate that in the
      diseases studied this morphofunctional diversity is associated with additional
      ultrastructural characteristics inherent to each disease. In
      paracoccidioidomycosis the proportion of vacuolated macrophages is significantly
      lower than in other diseases; this might indicate that in paracoccidioidomycosis
      the proportion of activated AM is smaller. We observed significant differences in
      the expression of MHC-II antigens. Silicosis, sarcoidosis, and allergic
      alveolitis do not differ significantly in the quantity of immunolabeled AM or in
      the distribution of the label. The percentage of AM from paracoccidioidomycosis
      that exhibit the MHC-II molecule is very low with poor immunolabeling. In this
      disease the low expression of the MHC-II molecule could be related to a decrease
      of the antigen presenting function by AM.

PMID- 7829962
TI  - Summary of the 5th International Congress on TNF and related cytokines:
      scientific advances and their medical applications.

PMID- 7829963
TI  - Cellular target of in vitro-induced suppressor cells derived from the spleen of
      Mycobacterium lepraemurium-infected mice and role of IFN-gamma in their
      development.
AB  - Unfractionated spleen cells from C3H mice infected a few weeks before with
      Mycobacterium lepraemurium developed a suppressor activity after overnight
      culture. This requires contact of plastic adherent cells with nonadherent cells
      distinct from T, B, or natural killer cells. The present study demonstrates that
      anti-interferon-gamma (IFN-gamma) monoclonal antibody and indomethacin totally
      abrogate the expression, although not the induction, of this activity.
      Furthermore, culture-induced suppressor cells selectively inhibit T lymphocyte
      proliferation, probably by altering the generation of interleukin-2 (IL-2)
      responsiveness through reduction of the affinity and density of high-affinity IL
      2 receptors on activated cells. These and other previously determined properties
      of culture-induced suppressor cells, similar to those of adherent suppressor
      cells detected in freshly harvested spleen cells at a later stage of M.
      lepraemurium infection, suggest a common precursor. If so, the present
      observations should help in defining a strategy to prevent the impairment of cell
      mediated immunity in infected mice.

PMID- 7829964
TI  - Inactivation of interleukin-8 by aminopeptidase N (CD13).
AB  - Aminopeptidase (APN) was found to degrade interleukin-8 (IL-8) and inactivate its
      chemotactic activity. The chemotactic activity of IL-8 was decreased by APN or
      neutrophil plasma membranes dose- and time-dependently. The chemotactic activity
      was not inactivated in the presence of bestatin or WM15 monoclonal antibody. The
      expression of IL-8 was measured by flow cytometry. On lipopolysaccharide (LPS)
      stimulation, IL-8 expression increased for 60 min and then decreased markedly. In
      contrast, on treatment with LPS and bestatin, the expression of IL-8 increased
      continuously for at least 120 min. These results suggest that the expression and
      release of IL-8 from phagocytic cells are regulated by the proteolytic effect of
      APN on IL-8.

PMID- 7829965
TI  - Interleukin-2 and human monocyte activation.
AB  - The recognition of the monocyte/macrophage-activating properties of IL-2 has
      broadened our image of the biological effects of this lymphokine from those of a
      T cell growth factor to those of a molecule with pleiotropic effects. The
      detailed analysis of the mechanisms of action of IL-2 including its biological
      effects on different cell types and the regulation of its receptors has increased
      dramatically the spectrum of the biological responses that can be modified by IL
      2. The regulation of the expression of the IL-2 receptor subunits differs in
      terms of response to extracellular stimuli and intracellular control, suggesting
      that the response to IL-2 will vary depending on the nature and extent of
      environmental stimulation. Furthermore, the fact that the IL-2R gamma chain can
      be part of the receptor for IL-4, IL-7, and perhaps other cytokines indicates
      that IL-2 may modulate the response of monocytes simply by binding or releasing
      the IL-2R gamma chain and thus modulating the responsiveness to IL-4 or IL-7.
      Conversely, the extent of utilization of IL-2R gamma chain by various cytokines
      may dictate the monocytic response to IL-2. In fact, the availability of IL-2R
      gamma chain seems to be the limiting factor in the response of monocytes to IL-2.
      Modulation of cytokine receptors is an integral part of the control of the IL-2
      response. The induction of CSF-1 receptor by IL-2 and the positive effect of CSF
      1 on the duration of the cytotoxic response in IL-2-stimulated monocytes are an
      interesting example of a synergistic interaction of potential physiological
      relevance. The response of monocytes to IL-2 can also be modulated by inhibitory
      circuits, such as those involving TGF-beta 1, IFN-gamma, and IL-4. However, IFN
      gamma and IL-4 can also activate monocytes and the timing and relative
      concentrations of the various cytokines may be critical variables in determining
      the ultimate monocyte phenotype. These studies have given us a glimpse of a very
      complex picture composed of multiple backgrounds and several players. However,
      the present information is not sufficient to make meaningful predictions of the
      resulting monocyte phenotype in an inflammatory reaction in which multiple
      cytokines are involved.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7829966
TI  - Inhalation exposure to isobutyl nitrite inhibits macrophage tumoricidal activity
      and modulates inducible nitric oxide.
AB  - Abuse of nitrite inhalants is common among male homosexuals and a history of
      abuse has been correlated with seropositivity to HIV and with the incidence of
      Kaposi's sarcoma among AIDS patients. The present study shows that inhalation
      exposure of mice to 900 ppm isobutyl nitrite for 45 min/day for 14 days
      compromised macrophage tumoricidal activity by up to 40% and it remained
      compromised for at least 7 days after terminating exposures. The inhalation
      exposures did not affect tumor cell binding but did inhibit inducible nitric
      oxide (NO zero). The NO zero synthase inhibitor NG-methyl-L-arginine totally
      inhibited both NO zero production and cytotoxicity, suggesting that reductions in
      NO zero due to inhalant exposure may be responsible for the reduced cytotoxic
      activity. Exposure to the inhalant increased constitutive production of tumor
      necrosis factor-alpha (TNF-alpha). TNF-alpha has been reported to stimulate the
      replication of HIV and the proliferation of Kaposi's sarcoma cells in vitro.

PMID- 7829967
TI  - Polar agents with differentiation inducing capacity potentiate tumor necrosis
      factor-mediated cytotoxicity in human myeloid cell lines.
AB  - Cotreatment or pretreatment of several human myeloid cell lines (KG1, HL60, U937,
      THP1) with the differentiation inducer DMSO was found to potentiate the
      antiproliferative and cytotoxic effects of TNF. In addition, TNF-resistant
      monocytic cell lines could be sensitized to TNF cytotoxicity by DMSO treatment.
      Other highly polar molecules, known to be potent differentiation inducers, showed
      similar effects to those of DMSO. The potentiating effect of DMSO was related
      neither to an up-regulation of TNF receptor expression nor to an alteration in
      the rate of TNF internalization and degradation. We present evidence that the TNF
      activities are p55 TNF receptor-mediated and are not due to insertion of TNF into
      lipid bilayers, an effect that could be susceptible to DMSO, as this component
      has been described to modify cell membrane characteristics. DMSO-induced
      potentiation of TNF cytostasis/cytotoxicity was restricted to myeloid leukemia
      cell lines. In non-myeloid cells such as fibrosarcomas, myosarcomas, thymomas, or
      carcinomas, DMSO was found either not to alter or to inhibit TNF-induced cell
      death. The latter results are in good agreement with data reported by others who
      suggested that DMSO could act as a scavenger of TNF-induced toxic radical
      formation. The potential correlation in myeloid cells between DMSO-induced
      changes in the cells' differentiation status and DMSO-enhanced TNF-susceptibility
      is discussed.

PMID- 7829968
TI  - Ligation of CD23 activates soluble guanylate cyclase in human monocytes via an L
      arginine-dependent mechanism.
AB  - Transduction through Fc epsilon R2/CD23 was analyzed in normal human monocytes
      using immunoglobulin E (IgE)-anti-IgE immune complexes (IgE ICs) and monoclonal
      antibodies (mAbs) to CD23. Anti-CD23 mAb and IgE IC triggered a time-dependent
      increase in cGMP and cAMP in interleukin-4-preincubated (CD23+) but not in
      unstimulated (CD23-) monocytes. Maximal cGMP and cAMP accumulations were observed
      10 and 20 min, respectively, after the onset of CD23 ligation. The increase in
      cGMP was inhibited with N omega-monomethyl-L-arginine (L-NMMA), which also
      partially affected cAMP accumulation. Addition of an anti-CD23 mAb Fab fragment
      inhibited the IgE IC- and the anti-CD23 mAb-induced cGMP and cAMP accumulation,
      confirming the engagement of CD23. In addition, IgE IC and anti-CD23 mAb induced,
      at least in some donors, a production of nitrite that was inhibited in the
      presence of L-NMMA. Taken together, these findings suggest a possible involvement
      of the nitric oxide synthase pathway in IgE IC-mediated activation of CD23+
      monocytes.

PMID- 7829969
TI  - Macrophages derived from C3H/HeJ (Lpsd) mice respond to bacterial
      lipopolysaccharide by activating NF-kappa B.
AB  - The effects of bacterial lipopolysaccharide (LPS) on macrophage gene expression
      are mediated in part by its ability to induce activation of transcription factor
      NF-kappa B. We compared the ability of LPS-treated macrophages from Lpsn (LPS
      responsive) C3H/HeN and Lpsd (LPS-hyporesponsive) C3H/HeJ mice to mobilize NF
      kappa B by electrophoretic mobility shift assays with oligonucleotide probes
      containing a unique NF-kappa B sequence from the promoter of inducible nitric
      oxide synthase (iNOS). In response to ng/ml concentrations of LPS, this probe
      bound proteins that appeared rapidly in the nuclei of thioglycollate-elicited
      macrophages and bone marrow-derived macrophage cell lines from both Lpsn and Lpsd
      mice. Only in macrophages from Lpsn mice, however, was LPS able to induce iNOS or
      tumor necrosis factor alpha. NF-kappa B-containing DNA-protein complexes from
      Lpsd macrophages were formed in lesser amounts than from Lpsn macrophages but
      shared the same composition, insofar as they displayed the same electrophoretic
      mobilities and content of heterodimers of p50/RelA (p65) and p50/c-rel. Two
      conclusions emerge from these findings: (1) NF-kappa B activity alone is not
      sufficient for induction of certain LPS-responsive genes and (2) An LPS-response
      pathway involving activation of NF-kappa B is preserved in Lpsd mice. The
      inability of cells from Lpsd mice to induce gene expression in response to LPS
      thus cannot be attributed to inability to activate NF-kappa B.

PMID- 7829970
TI  - Expression of both types of human interleukin-8 receptors on mature neutrophils,
      monocytes, and natural killer cells.
AB  - cDNA cloning revealed the presence of two related but distinct types of human
      interleukin-8 (IL-8) receptors, type I (type A) and type II (type B). By
      immunizing rabbits with glutathione-S-transferase fused with the NH2-terminal
      domain of each type of IL-8 receptor, we prepared polyclonal antibodies that
      specifically recognized the NH2-terminal domain of each type of IL-8 receptor.
      Immunofluorescence analysis of human peripheral blood leukocytes demonstrated
      that mature granulocytes except eosinophils express both types of IL-8 receptors.
      A majority of monocytes and CD16+ natural killer (NK) cells in peripheral blood
      were stained with both antibodies, whereas CD3+ T or CD20+ B lymphocytes in
      peripheral blood or CD34+ cells in cord blood were not stained with either
      antibody. These results suggest that both types of human IL-8 receptors were
      coordinately and selectively expressed in mature granulocytes, monocytes, and
      CD16+ NK cells.

PMID- 7829971
TI  - Apoptosis in leukocytes.
AB  - All cells of the hematopoietic system have finite life spans, shorter by far than
      that of the host. They end their lives by committing a form of cellular suicide
      or programmed cell death. The morphology of this process is considerably
      different from that of necrosis and is called apoptosis. Apoptotic cells undergo
      a stereotyped sequence of changes, including shrinkage and nuclear collapse. The
      cell is quickly recognized and eaten by a phagocyte, without the elicitation of
      an inflammatory response. Although most cells have specific triggers of
      apoptosis, the killer T cell seems able to induce apoptosis in any cell it
      recognizes. The process of apoptosis is regulated by cytokines, and may be
      modulated both in vitro and in vivo.

PMID- 7829972
TI  - In vivo activation of heterophil function in chickens following injection with
      Salmonella enteritidis-immune lymphokines.
AB  - We have previously shown that increased resistance to Salmonella enteritidis
      organ infectivity in day-old chicks was conferred by the immunoprophylactic
      administration of S. enteritidis-immune lymphokines (ILK). This resistance was
      associated with a significant increase in the number of circulating heterophils 4
      h after ILK injection. The objective of the present study was to evaluate
      heterophil function following the administration of ILK in day-old chicks.
      Significant increases (P < 0.001) in adherence, chemotaxis, and phagocytosis of
      S. enteritidis were found with heterophils isolated from ILK-injected chickens
      compared to the heterophils isolated from birds injected with either pyrogen-free
      saline or lymphokines from non-immune T cells. After phagocytosis, the
      heterophils from the ILK-injected chickens were also able to kill significantly
      greater numbers of S. enteritidis more rapidly than did the heterophils from the
      saline-injected control birds (within 30 min, control cells killed 21.89% of the
      bacteria whereas ILK-treated cells killed 88.22%). We also found that the
      heterophils from the ILK-injected birds were more efficient killers of S.
      typhimurium, S. gallinarum, and E. coli. These results strongly suggest that the
      protection against S. enteritidis organ invasion induced by the prophylactic
      treatment of day-old chicks with ILK involves activated heterophils which migrate
      rapidly to the inflammatory stimulus where they phagocytize and kill the
      bacteria.

PMID- 7829973
TI  - Heterodimers of the calcium-binding proteins MRP8 and MRP14 are expressed on the
      surface of human monocytes upon adherence to fibronectin and collagen. Relation
      to TNF-alpha, IL-6, and superoxide production.
AB  - The 27E10 antigen is a heterodimer of MRP8 and MRP14, two Ca(2+)-binding proteins
      related to the S-100 protein family. Previous studies have shown that 27E10
      epitope-bearing monocyte subsets are prevalent in early acute but absent in
      chronic inflammatory conditions. These observations further provide an impetus
      for identifying the cellular mechanisms responsible for the appearance of
      different monocyte subpopulations during inflammation. Therefore this in vitro
      study was carried out to investigate the influence of adhesion in inducing 27E10
      positive subsets. In adhesion assays the role of 27E10 antigen in spontaneous
      adherence was obvious, as a monoclonal antibody directed against the 27E10
      antigen significantly inhibited the adherence of monocytes to collagen and
      fibronectin. In contrast, these extracellular matrix (ECM) proteins induce the
      cell surface expression and association of 27E10 antigen with cytoskeleton (CSK),
      detected by flow cytometry and confocal laser scan microscopy, respectively.
      Similar results were obtained on cross-linking with specific antibodies, thus
      showing involvement of the integrin molecules VLA-2 and VLA-4. In addition, the
      association with CSK could be confirmed by differential detergent extraction. The
      observed redistribution of 27E10 antigen guided by collagen compared with
      fibronectin was also paralleled by an augmented release of inflammatory cytokines
      interleukin-6, tumor necrosis factor alpha, and superoxide anions. Thus, this
      study demonstrates that under inflammatory conditions the interactions of
      extravasating monocytes with the ECM may induce an activated phenotype of
      monocytes marked by 27E10.

PMID- 7829974
TI  - The endoperoxides/TxA2 analogue, U46619, inhibits human polymorphonuclear
      leukocyte function.
AB  - The effects of the stable analogue of TxA2, U46619, on polymorphonuclear
      leukocyte (PMN) function were investigated. U46619, at micromolar concentrations,
      inhibited fMLP-stimulated aggregation, beta-glucuronidase release, and superoxide
      production. fMLP-induced LTB4 synthesis was also inhibited. U46619 did not modify
      intracellular Ca2+ increase induced by fMLP in Fura-2-loaded PMN, suggesting that
      early events of cell activation were not involved. In fact, U46619 also inhibited
      aggregation, beta-glucuronidase release, superoxide anion and LTB4 production
      induced by the calcium ionophore A23187. By comparison with the specific 5
      lipoxygenase inhibitor, L-663,536, which prevented LTB4 synthesis without
      affecting degranulation, we excluded the impairment of PMN function by U46619 as
      a consequence of the reduction of this endogenous agonist. TLC separation of
      lipid extracts from [3H]-AA-loaded PMN, stimulated by A23187, showed significant
      reduction of the radioactivity associated with authentic free AA, suggesting that
      U46619 could interfere with mechanisms regulating AA release from membrane
      phospholipids. This suggestion is also supported by the observation that
      manoalide, a standard inhibitor of phospholipase A2, similarly to U46619,
      inhibits beta-glucuronidase release from stimulated PMN. Prostaglandin
      endoperoxides, produced by cells participating in inflammatory reactions, might
      therefore play a role in modulating PMN activities.

PMID- 7829975
TI  - LPS inhibits the intracellular growth of Legionella pneumophila in thioglycolate
      elicited murine peritoneal macrophages by iron-dependent, tryptophan-independent,
      oxygen-independent, and arginine-independent mechanisms.
AB  - Thioglycolate-elicited murine macrophages from genetically susceptible A/J mice
      activated with lipopolysaccharide (LPS) and infected with Legionella pneumophila
      in vitro evince marked inhibition of intracellular growth of this bacterium. The
      mechanism of inhibition by LPS-activated macrophages in terms of replication of
      this intracellular pathogen is unclear. LPS activation of murine macrophages
      induced a downshift in transferrin receptor (TfR) expression and reduction in
      cellular iron content, and this was correlated with augmented intracellular
      growth of Legionella in the cells. When LPS-stimulated macrophages were first
      saturated with iron, partial reversion of L. pneumophila growth restriction was
      observed. However, an excess of exogenous L-tryptophan (Trp) did not reverse this
      growth inhibition, nor did supplementation of the macrophage culture medium with
      both iron and Trp. The antilegionella activity of the macrophages induced by LPS
      activation was independent of reactive oxygen intermediates (ROI), since the
      scavengers catalase, superoxide dismutase, mannitol, and thiourea had no effect
      on growth restriction. Likewise, notwithstanding the ability of LPS-activated
      macrophages to synthesize reactive nitrogen intermediates (RNI), which was
      inhibited by L-arginine analogs NG-monomethyl-L-arginine and L-aminoguanidine),
      as well as by incubation in arginine-free medium, their ability to inhibit the
      intracellular replication of L. pneumophila was not affected. Thus, we conclude
      that LPS-activated macrophages inhibit the intracellular growth of L. pneumophila
      partially by iron-dependent, Trp-independent, and ROI- and RNI-independent
      mechanisms. We also suggest that additional unknown mechanisms are involved,
      since complete reversion was not obtained.

PMID- 7829976
TI  - Immunocytochemical localization of granulin-1 to mononuclear phagocytic cells of
      the teleost fish Cyprinus carpio and Carassius auratus.
AB  - A new class of low-molecular-weight cysteine-rich regulatory growth factors,
      designated granulins, has been isolated from hematopoietic tissues of a teleost
      fish (Cyprinus carpio) and structurally characterized. Granulin-1, the
      predominant form found in carp spleen, was used to raise polyclonal antibodies in
      rabbits and to establish a radioimmunoassay. This permitted preliminary tissue
      distribution studies of granulin-1 to be undertaken in carp (Cyprinus carpio) and
      goldfish (Carassius auratus). Granulin-1 immunoreactivity was found in the
      melanomacrophage centers of the spleen and head kidney. Carp tissues anatomically
      involved in the first line of defense against infection, including skin, gills,
      gut, and also heart, showed intense granulin-1 immunoreactive staining within
      presumptive macrophage cells. Granulin-1 immunoreactive macrophages prepared from
      goldfish spleen and head kidney adhered to glass slides, actively phagocytosed
      carbon particles, and contained granulin-1 immunoreactivity as well as abundant
      endogenous peroxidase activity. This study demonstrates that granulin-1 is
      synthesized and stored in macrophages/monocytes of spleen, head kidney, and
      peripheral tissues of teleost fish.

PMID- 7829977
TI  - Enhancing medical database security.
AB  - A methodology for the enhancement of database security in a hospital environment
      is presented in this paper which is based on both the discretionary and the
      mandatory database security policies. In this way the advantages of both
      approaches are combined to enhance medical database security. An appropriate
      classification of the different types of users according to their different needs
      and roles and a User Role Definition Hierarchy has been used. The experience
      obtained from the experimental implementation of the proposed methodology in a
      major general hospital is briefly discussed. The implementation has shown that
      the combined discretionary and mandatory security enforcement effectively limits
      the unauthorized access to the medical database, without severely restricting the
      capabilities of the system.

PMID- 7829978
TI  - Radiation dose and risk in screening mammography.
AB  - Screening mammography has not yet become a standard procedure. There are great
      variations in image quality and radiation dose. Mean glandular dose has become
      the most frequently used description of radiation dose in screening mammography.
      Because of the low energy x-ray beam required for the procedure, the use of mean
      glandular dose as the radiation exposure indicator may cause a misunderstanding
      of the dose-risk relationship and result in confusion about radiation exposure
      and the risk of induced neoplasm. Data are presented to show that increases in
      both maximum glandular dose and imparted energy are greater than the increases in
      mean glandular dose with comparable increases in breast thickness. In the future,
      an indication of total imparted energy should replace the use of mean glandular
      dose as the standard for describing radiation dose in screening mammography.

PMID- 7829979
TI  - Health service production in the view of medical informatics.
AB  - Medical informatics aims to improve the process and the result of health care
      delivery, both in its theoretical and practical aspects through the application
      of formal methods and concepts of informatics and the utilization of up-to-date
      information and communication technology. As part of a theoretical framework this
      paper deals with the factors of production, the constitutive criteria and the
      formal aspects of health service production in the view of medical informatics.

PMID- 7829980
TI  - Computer analysis of auditory brainstem responses by using advanced pattern
      recognition.
AB  - Automatic peak detection of auditory brainstem responses is a multistage process.
      The main task is the detection of the pedestal peak, which is a broad peak
      filtered out from the auditory brainstem signal. Special validation stages have
      been used to determine whether a real response is present, and if so, peak V is
      detected. The system reaches 90% accuracy with random clinical material.

PMID- 7829981
TI  - Decision trees based on automatic learning and their use in cardiology.
AB  - Computerized information systems, especially decision support systems, have
      become an increasingly important role in medical applications, particularly in
      those where important decision must be made effectively and reliably. But the
      possibility of using computers in medical decision making is limited by many
      difficulties, including the complexity of conventional computer languages,
      methodologies and tools. Thus a conceptual simple decision making model with the
      possibility of automating learning should be used. In this paper we introduce a
      cardiological knowledge-based system based on the decision tree approach
      supporting the mitral valve prolapse determination. Prolapse is defined as the
      displacement of a bodily part from its normal position. The term mitral valve
      prolaps (PMV), therefore, implies that the mitral leaflets are displaced relative
      to some structure, generally taken to the mitral annulus. The implications of the
      PMV are the following: disturbed normal laminar blood flow, turbulence of the
      blood flow, injury of the chordae tendinae, the possibility of thrombus's
      composition, bacterial endocarditis, and finally hemodynamic changes defined as
      mitral insufficiency and mitral regurgitation. Uncertainty persists about how it
      should be diagnosed and about its clinical importance. It is our deep belief that
      the echocardiography enables properly trained experts armed with proper criteria
      to evaluate PMV almost 100%. But unfortunately, there are some problems concerned
      with the use of echocardiography. In that manner we have decided to start a
      research project aimed at finding new criteria and enabling the general
      practitioner to evaluate PMV using conventional methods and to select potential
      patients from the general population.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7829982
TI  - An evaluation of hospital emergency department (HED) adherence to universal
      precautions.
AB  - A longitudinal cross sectional study of Hospital Emergency Department (HED)
      procedures over a nine month period was conducted. A total of 1,541 procedures
      were observed on 56 randomly selected 8-h work shifts. Shifts were distributed:
      34% day shift; 34% evening shift; and 32% on the night shift. Observations on the
      evening shift were oversampled to capture an adequate number of trauma patients.
      Observations were distributed: 33% day shift; 39% evening shift; and 28% on the
      night shift. Measurements included: type of procedure; adherence to specific
      barrier technique, i.e., use of gloves, gowns, masks, and eye protection; and
      occurrence of adverse exposure. Ten types of HED procedures were documented and
      analyzed. Computerized tracking of study observations established periodic rates
      of HED health care worker (HCW) adherence to universal precautions. These data
      are important for internal quality control/assurance programs and rate
      comparisons within and across institutions over time. The longitudinal evaluation
      of the database revealed that glove compliance increased over the period of the
      study and adverse exposure decreased. Conducting ongoing or periodic
      observational studies of this kind are important and necessary in order to gauge
      HED response to the epidemiologic challenges of urban society.

PMID- 7829983
TI  - ANF(1-28) is a potent suppressor of pro-opiomelanocortin (POMC) mRNA but a weak
      inhibitor of beta EP-LI release from AtT-20 cells.
AB  - Controversies remain whether atrial natriuretic factor (ANF) may play a role in
      modulating the release of POMC derived peptides from pituitary corticotrophs.
      Employing AtT-20 mouse pituitary tumour cells, we report here the effects of rat
      ANF(1-28) and sodium nitroprusside (SNP), both of which augment cellular levels
      of cGMP through activating particulate and soluble guanylyl cyclases
      respectively, on the expression of POMC mRNA abundance. Furthermore, the cellular
      contents and secretion of (beta endorphin-like immunoreactivity) beta EP-LI from
      these cultures were also examined. Whereas the abundance of POMC mRNA was found
      to be markedly suppressed following 4h of incubation with rANP(1-28) (0.01 to 1
      microM), SNP (0.1 to 10 microM) and dibutyryl-cGMP (1 to 100 microM) in a dose
      related manner, only a modest reduction in the release and cell contents of beta
      EP-LI was found in some of these cultures. It is also of interest to note that in
      all the cases examined, the inhibitory effect was associated with a significant
      suppression of cAMP levels in the cultures. Taken together, our present findings
      suggest that ANF may play a more important role in suppressing the production
      than the release of POMC related peptides from AtT-20 cells. Thus, it raises the
      possibility that hypothalamic ANF may likewise modulate the function of the
      pituitary-adrenal axis through exerting a greater effect on inhibiting the
      production than the secretion of pituitary ACTH.

PMID- 7829984
TI  - Evidence for a novel source of relaxin: atrial cardiocytes.
AB  - Antibody-directed, complement-induced erythrocyte lysis (reverse hemolytic plaque
      assay) around atrial cardiocytes was used to determine whether this cell type
      possesses the capacity to secrete the insulin-like hormone relaxin. After 2h of
      incubation, 33 +/- 4% (n = 3) of cardiocytes derived from the atria of neonatal
      rats secreted detectable amounts of immunoreactive relaxin (i.e. formed plaques)
      when cultured in monolayers. Increased culture time of cardiocytes failed to
      increase the fraction of cardiocytes that secreted relaxin. The cumulative amount
      of relaxin secreted after 3h of incubation (plaque area) was 31% greater (P <
      0.05) than the amount of hormone present after 1h of incubation, evidence of
      sustained peptide secretion by cultured cardiocytes. These data suggest that the
      source of the endogenous ligand for the specific and high-affinity relaxin
      receptors located in rat atria is the atrial cardiocyte itself. Therefore,
      relaxin may act via autocrine and/or paracrine routes to regulate cardiovascular
      structure and/or function.

PMID- 7829985
TI  - Cells cultured from the growing tip of red deer antler express alkaline
      phosphatase and proliferate in response to insulin-like growth factor-I.
AB  - Deer antler growth provides a unique natural model of rapid and complete bone
      regeneration. In this study, the distal antler tips of male red deer (Cervus
      elaphus) were collected post-mortem during the annual growth period (April
      August), and an in vitro system established for the culture of cells from three
      regions; the inner layer of the perichondrium, the reserve mesenchyme and the
      cartilage zone. Alkaline phosphatase (ALP) expression by cultured cells, as
      demonstrated by enzyme histochemistry and biochemical assay, reflected the stage
      of cellular differentiation. ALP activity was highest in cells cultured from the
      hypertrophic cartilage region (3.6 +/- 0.2 mumol/micrograms cell protein/minute),
      and lowest in undifferentiated mesenchymal cells (0.3 +/- 0.01 mumol/microgram
      cell protein/minute). ALP expression was lost with passage in culture. Levels of
      ALP activity in cultured cells correlated with the pattern and extent of enzyme
      expression in tissue sections as demonstrated by histochemical staining. Insulin
      like growth factor (IGF)-I (10(-9)M-10(-7)M) was found to be mitogenic for
      cultured cells from all three zones as shown by increased incorporation of
      [3H]thymidine into DNA. These results demonstrate that cells from three different
      regions of the antler tip can be maintained in culture, and that antler cells
      share certain phenotypic characteristics of growth plate chondrocytes. These data
      provide further evidence of a role for IGF-1 in the regulation of antler growth.
      Antler regrowth is a potentially useful model for the study of the factors that
      regulate bone formation.

PMID- 7829986
TI  - The time since castration influences the effects of short-term starvation on
      gonadotrophin secretion in male rats.
AB  - Short-term starvation suppresses the pituitary-testicular function in rats,
      evidently through inhibition of gonadotrophin-releasing hormone (GnRH) release.
      However, when gonadotrophin secretion is strongly enhanced, e.g. after
      castration, starvation does not suppress gonadotrophins. To test whether the time
      since castration affects the pituitary response to starvation, adult male rats
      were totally deprived of food for five days (only water allowed) immediately
      (acute castration) or two weeks after castration (chronic castration). The
      pituitary contents of GnRH receptors were decreased by starvation in sham
      operated animals, unaffected in acutely castrated rats, but increased in
      chronically castrated animals, in comparison with appropriate controls (P <
      0.01). Castration per se increased steady-state mRNA levels of the common alpha
      chain and the LH and FSH beta-chains in all groups studied. The only consistent
      effect of starvation on these parameters was the 1.7 to 2-fold increase in the
      pituitary content of LH beta-subunit mRNA in acutely and chronically castrated
      rats (P < 0.01). Starvation alone suppressed LH secretion, acute castration
      eliminated this effect, but in chronically castrated rats, the starvation effect
      was stimulatory. Starvation did not affect FSH secretion in sham-operated and
      acutely castrated rats, but after chronic castration, the effect was stimulatory.
      In conclusion, the overall effect of starvation on gonadotrophins shifts
      gradually after castration from suppression, in sham-operated rats, to
      stimulation, in chronically castrated animals. Parallel changes in pituitary GnRH
      receptors suggest similar changes in GnRH secretion. Hence, starvation has both
      negative and positive effects on the GnRH-gonadotrophin-axis. The negative effect
      is evidently androgen-dependent and dominates in testes-intact animals. After
      chronic castration, only the positive, non-androgen dependent, stimulatory effect
      remains.

PMID- 7829987
TI  - Genistein but not staurosporine can inhibit the mitogenic signal evoked by
      lithium in rat thyroid cells (FRTL-5).
AB  - Long-term administration of lithium is one of the well-known causes of goiter. It
      can stimulate DNA synthesis in rat thyroid cells (FRTL-5) treated with thyroid
      stimulating hormone (TSH). To investigate the mitogenic signal transduction
      system activated by lithium, lithium-induced DNA synthesis and Ca2+ influx were
      studied using two protein kinase inhibitors, genistein as a specific tyrosine
      kinase inhibitor and staurosporine as a potent inhibitor of protein kinase C.
      Genistein but not staurosporine blocked the DNA synthesis induced by lithium in
      TSH-primed cells but neither compound had any effect on the Ca2+ entry stimulated
      by lithium. Genistein clearly attenuated the phosphotyrosine content of the 175
      kDa substrate in the presence of lithium but staurosporine failed to do so.
      Moreover, lithium could also stimulate DNA synthesis in protein kinase C down
      regulated cells. These data demonstrate that lithium may require the activation
      of a particular genistein-sensitive kinase, possibly a tyrosine kinase, to induce
      cell proliferation. It is suggested that the phorbol ester-sensitive protein
      kinase C family might not participate in the mitogenic signal transduction
      pathway activated by lithium.

PMID- 7829988
TI  - In vivo diuretic effect of a new non-peptide arginine vasopressin antagonist, OPC
      31260, in conscious rats.
AB  - The present study was undertaken to determine whether a non-peptide arginine
      vasopressin (AVP) antagonist (5-dimethylamino-1-[4-(2-methylbenzoylamino)benzoyl]
      2,3,4,5-tetra hydro-1H- benzazepine; OPC-31260) antagonizes the antidiuretic
      action of endogenous and exogenous AVP in conscious rats. OPC-31260, given orally
      at a dose of 5 mg/kg or higher, increased urinary volume (UV) and reduced urinary
      osmolality (Uosm) in a dose-dependent manner, in rats acutely denied access to
      water. Minimal Uosm was obtained 1-2 h after oral administration of OPC-31260.
      OPC-31260 caused sustained water diuresis for more than 12 h when water was
      available ad libitum since OPC-31260 (30 mg/kg) reduced Uosm to less than 230
      mOsmol/kg H2O, significantly less than the control value of 600 mOsmol/kg H2O.
      Water deprivation for 24 h increased plasma AVP levels to 7.2 pmol/l and
      increased Uosm to 2160 mOsmol/kg H2O. In such water-deprived rats, oral
      administration of OPC-31260 at 100 mg/kg was diuretic; it markedly increased free
      water clearance and decreased Uosm to 202 mOsmol/kg H2O. In homozygous
      Brattleboro rats (with inherited AVP deficiency), given free access to water,
      subcutaneous infusion of the V2 agonist 1-deamino-8-D-AVP (dDAVP) at a rate of 1
      ng/h markedly decreased UV to 12.6 from 148.7 ml/day and increased Uosm to 1762
      from 231 mOsmol/kg H2O. OPC-31260 (30 mg/kg) promptly increased UV and reduced
      Uosm to levels similar to those before the administration of dDAVP; repeated OPC
      31260 treatment had sustained effects. These results indicate that OPC-31260 is
      an orally effective non-peptide AVP antagonist to the antidiuretic action of AVP
      in the conscious rat.

PMID- 7829989
TI  - Actions of somatotrophin on oxytocin and progesterone release from the
      microdialysed bovine corpus luteum in vitro.
AB  - In the present investigation, the effect of recombinant (BST) and pituitary
      derived (bGH) bovine somatotrophin on progesterone and oxytocin release was
      examined. Individual copora lutea (CL) were obtained from cows at different
      stages of the oestrous cycle (days 5-7, 8-12 and 15-18) and also from early
      pregnancy (days 60-120) and were implanted with an in vitro microdialysis system
      (MDS). Perfusion with BST for 60 min (0.05, 0.5 and 5 mumol/l) induced a dose
      dependent stimulation of progesterone release. Release of oxytocin from CL was
      significantly stimulated by BST at all dose levels. BST (0.5 mumol/l) stimulated
      progesterone release most during the early and mid-luteal phases and oxytocin
      release especially during the early luteal stage (days 5-7) of the oestrous
      cycle. CL from early pregnancy (days 60-120) treated with BST showed a
      significant response in progesterone and oxytocin release. bGH showed comparable
      effects. Our results suggest that somatotrophin acts directly on the secretory
      function of bovine CL in the MDS, specifically during the early luteal stage
      (days 5-7) of the oestrous cycle and early pregnancy (days 60-120). Somatotrophin
      may therefore have physiologically relevant effects associated with the
      development and maintenance of luteal function.

PMID- 7829990
TI  - Stimulation by insulin-like growth factor-I of creatine kinase activity in
      skeletal-derived cells and tissues of male and female rats.
AB  - Insulin-like growth factor-I (IGF-I) has been reported to mediate the effects of
      oestradiol-17 beta in the osteoblast-like osteosarcoma cell line ROS 17/2.8 and
      to stimulate directly cell proliferation in cell cultures derived from rat
      calvaria. Few data are available on the role of IGF-I in androgen stimulation of
      cultured skeletal cells and in oestrogen and androgen stimulation of bone and
      cartilage in vivo. The purpose of the present study was to compare the effect of
      IGF-I in rats in vivo with its effect in vitro on calvarial bone cells from
      females (responding only to oestrogens) and from males (responding only to
      androgens, such as testosterone and dihydrotestosterone). We found that IGF-I
      stimulated, in a dose- and time-dependent manner, the specific activity of
      creatine kinase (CK, a marker of skeletal cell division), in both female and male
      calvarial bone cells, in ROS 17/2.8 cells and in epiphyseal cartilage cell
      cultures. Maximal stimulation occurred at 30 or 100 nM within 1-2 h after
      stimulation. In ROS 17/2.8 cells, IGF-I stimulated [3H]thymidine incorporation,
      after 22 h of treatment, in parallel with CK activity. IGF-II, at higher doses
      than IGF-I (maximal stimulation at 300 nM), stimulated CK specific activity in
      female- and male-derived calvarial cell cultures. When IGF-I (50 nM) was applied
      together with oestradiol-17 beta (30 nM) or with dihydrotestosterone (300 nM)
      there was no additional response in the cultures.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7829991
TI  - Studies on the use of cultured cells in a bioassay for parathyroid hormone.
AB  - Measurement of parathyroid hormone (PTH) is important for diagnosing hyper- and
      hypoparathyroidism. The move to two-site immunometric assays that detect the
      whole molecule has improved the discrimination of these conditions but these
      assays may be too restrictive because some PTH fragments that are biologically
      active may not be detected. In addition, PTH-like peptide of malignancy, an
      important cause of malignancy-associated hypercalcaemia, is not detected by the
      two-site assays. Experiments were performed to set up a simple, robust and
      inexpensive bioassay for PTH, exploiting a kidney cell line and using cyclic AMP
      or an eluted stain assay as the end point. Of the 12 cell lines tested, an
      opossum kidney (WOK) cell line showed the most promise. Despite optimization of
      the procedure to include pre-treatment with dexamethasone, insulin and PTH,
      followed by incubation in the presence of 5'-guanylimidodiphosphate, isobutyl-1
      methylxanthine and forskolin, the WOK cells showed insufficient sensitivity for
      use in a cultured cell bioassay for PTH in human serum. In addition, the cells
      were less sensitive to PTH-like peptide precluding their use for an assay for
      this molecule.

PMID- 7829992
TI  - Role of reductase and aromatase in sex determination in the red-eared slider
      (Trachemys scripta), a turtle with temperature-dependent sex determination.
AB  - In many turtles the temperature during the middle of incubation determines the
      gonadal sex of the hatchling. In the red-eared slider turtle (Trachemys scripta),
      an incubation temperature of 26 degrees C results in all male offspring, whereas
      an incubation temperature of 31 degrees C results in all female offspring; at
      temperatures intermediate to these (e.g. 29, 29.2, 29.4 degrees C) a mixed sex
      ratio is obtained. Administration of exogenous oestrogens will overcome the
      effects of an all-male producing incubation temperature to cause female sex
      determination, whereas administration of exogenous dihydrotestosterone (DHT) or
      testosterone to eggs incubating at an all-female temperature will have no
      discernible effect. Administration of DHT will cause male sex determination only
      if administered at intermediate incubation temperatures whereas administration of
      testosterone to eggs incubating at all male-producing and male-biased
      intermediate temperatures results in a significant number of female offspring, an
      effect presumably due to aromatization of testosterone to oestradiol (OE2). Since
      testosterone serves as the precursor to both DHT and OE2, being metabolized by
      reductase and aromatase respectively, three experiments were conducted to
      determine whether various putative reductase and aromatase inhibitors would
      overcome the effect of incubation temperature. First, while administration of
      testosterone to eggs incubating at all male-producing and male-biased
      intermediate temperatures produced females in a dose- and temperature-dependent
      manner, significant numbers of intersex individuals resulted from high dosage
      testosterone treatment to eggs incubating at a female-biased intermediate
      temperature. The reductase inhibitors 4MA and MK906 were capable of producing
      female offspring if administered at intermediate temperatures, but not in a dose
      dependent fashion. Administration of the aromatase inhibitors CGS16949A and
      CGS20267 resulted in male offspring at both female-biased intermediate and at all
      female-producing temperatures in a dose-dependent fashion. Second, similar
      findings were obtained with combined doses of testosterone and reductase or
      aromatase inhibitors. Combined treatment of eggs at male-biased intermediate
      incubation temperatures with testosterone and reductase inhibitor resulted in
      female hatchlings, whereas combined treatment of testosterone and aromatase
      inhibitor at both female-biased intermediate and at all female-producing
      temperatures resulted in male hatchlings.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7829993
TI  - Thyroid iodide transport is reduced by administration of monoamine oxidase A
      inhibitors to rats.
AB  - The present work was addressed to study a possible relationship between monoamine
      oxidase (MAO) and the thyroid iodide transport mechanism. Normal rats treated
      with clorgyline (a selective MAO-A inhibitor) or tranylcypromine (a non-selective
      MAO inhibitor) showed a significantly diminished thyroid MAO activity, while
      deprenyl and pargyline (MAO-B inhibitors) did not modify the thyroidal enzyme
      activity with respect to the control group. Under these conditions, in vivo
      iodide transport was reduced both by clorgyline and tranylcypromine
      administration whereas it remained unchanged after treatment with MAO-B
      inhibitors. The effect of MAO inhibitors on thyroid MAO activity and in vivo
      iodide transport was also evaluated in rats treated with exogenous thyrotrophin
      (TSH) after endogenous TSH secretion blockade produced by T4 administration. In
      this condition, thyroid MAO activity was significantly lowered by clorgyline and
      was not modified by deprenyl. In contrast to the results observed in normal rats,
      in vivo iodide transport in TSH-treated rats remained unaltered after treatment
      either with clorgyline or deprenyl. MAO activity evaluated in bovine thyroid
      follicles in primary culture was highly sensitive to low concentrations of
      clorgyline (< 10 nmol/l) and relatively insensitive to deprenyl, a finding that
      indicates a predominance of the MAO-A isoform in the follicular cells in culture.
      When clorgyline (0.1 and 1 mumol/l) or deprenyl (1 mumol/l) were added to the
      culture medium, no modifications in the active transport of iodide were observed.
      These results indicate the absence of a direct linkage between thyroid MAO
      activity and the active iodide transport.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7829994
TI  - Maternal plasma levels of human chorionic gonadotrophin, oestradiol and
      progesterone in multifetal pregnancies before and after fetal reduction.
AB  - The aim of the study was to investigate the circulating levels of human chorionic
      gonadotrophin (hCG), oestradiol (OE2) and progesterone in multifetal pregnancies
      before and after embryo reduction. The levels of hCG, OE2 and progesterone were
      measured in plasma samples obtained from two groups of pregnant women: (i)
      singleton (n = 17), twin (n = 15) and triplet (n = 5) pregnancies achieved
      following superovulation; and (ii) multifetal pregnancies (three to ten embryos)
      undergoing fetal reduction to twin pregnancies (n = 31). The median value for
      each analyte at each gestational age in twin pregnancies was defined and used to
      derive multiples of the median (MoMs) for each analyte in samples obtained from
      multifetal pregnancies before and after reduction. The levels of hCG, OE2 and
      progesterone were significantly associated with the number of fetuses. Prior to
      reduction, the median MoMs for hCG, OE2 and progesterone were 1.54, 0.99 and 1.11
      respectively. After reduction to twins the median MoMs decreased to 0.84 for hCG,
      0.37 for progesterone and 0.51 for OE2. These data suggest that (i) the
      circulating levels of hCG, OE2 and progesterone increase with conceptus number;
      (ii) placental tissue does not remain active following fetal reduction; and (iii)
      the rate of steroid metabolism is increased in multiple pregnancy and remains
      elevated following fetal reduction.

PMID- 7829995
TI  - Regulation of oxytocin production by purified adult rat Leydig cells in vitro:
      effects of LH, testosterone and lipoproteins.
AB  - The aim of the present study was to determine whether LH stimulates oxytocin
      production by adult rat Leydig cells directly or indirectly via testosterone.
      Purified adult rat Leydig cells were cultured in the presence or absence of 0.1
      ng/ml LH or 1, 10 or 100 ng/ml testosterone for 22 h. Culture medium was
      collected at 2-hourly intervals and assayed for oxytocin and testosterone. In the
      presence of LH, Leydig cells produced significantly higher levels of both
      testosterone (basal production 1.4 +/- 0.13 ng, LH-stimulated 4.1 +/- 0.13
      ng/10(6) cells per 2 h) and oxytocin (basal production 8.3 +/- 1.2 pg, LH
      stimulated 20.2 +/- 1.3 pg/10(6) cells per 2 h). Testosterone also stimulated
      oxytocin secretion. However, the increase was smaller compared with that seen
      with LH and was not found to be dose-dependent. Furthermore, testosterone
      production was only significantly increased by LH during the first 10 h of the 22
      h culture period whereas LH stimulated oxytocin production throughout the whole
      culture period. To further determine the effect of LH on oxytocin production,
      cultures were performed in the presence of LH and/or 400 microM
      aminoglutethimide. In the presence of aminoglutethimide both the basal and LH
      stimulated production of testosterone was significantly reduced. However, in the
      same cultures aminoglutethimide did not alter either the basal or LH-stimulated
      production of oxytocin. These data show that LH does not act via testosterone to
      stimulate oxytocin production and therefore acts directly or by some alternative
      indirect mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7829996
TI  - Regulation of parathyroid hormone-related protein production in a human lung
      squamous cell carcinoma line.
AB  - The synthesis and release of parathyroid hormone-related protein (PTHrP) could be
      influenced in a paracrine or autocrine manner by substances present around or
      inside tumours, such as bone or stromal cell-derived cytokines, factors produced
      by the tumour itself or by peritumoural inflammatory cells. We investigated the
      effects of various cytokines known to be synthesized by osteoblasts, stromal
      cells, leucocytes or cancer cells, on PTHrP production by the human lung squamous
      cell carcinoma line BEN. The influence of tumour necrosis factor-alpha (TNF
      alpha) and interleukin-6 (IL-6) was studied, and compared with those of insulin
      like growth factors-I and -II (IGF-I, IGF-II), or macrophage- or granulocyte
      macrophage colony-stimulating factors (M-CSF, GM-CSF). TNF-alpha caused a 1.9 +/-
      0.1-fold increase in immunoreactive PTHrP production, which was maximal by 24 h
      of incubation. IL-6 caused a 2.3 +/- 0.2-fold increase, which was maximal by 16
      h. These effects, which were time- and concentration-dependent, were blocked by
      monoclonal antibodies raised against the corresponding cytokine. An increase of
      PTHrP mRNA was found in IL-6-treated cells. IGF-I and IGF-II increased PTHrP
      production by 2.0 +/- 0.3- and 2.3 +/- 0.1-fold respectively. Neither M-CSF nor
      GM-CSF altered PTHrP production up to 64 h of incubation. PTHrP production was
      not affected by varying extracellular calcium concentrations, but was decreased
      by incubation with 100 nmol/l dexamethasone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7829997
TI  - Endothelin-1 is involved in the transient hypoparathyroidism seen in patients
      undergoing thyroid surgery.
AB  - We have studied the serial changes in plasma endothelin (ET)-1, serum parathyroid
      hormone (PTH) and serum calcium concentrations during surgery in 20 patients
      undergoing a hemithyroidectomy for thyroid carcinoma. The plasma ET-1
      concentrations increased within the first 24 h following surgery in 18 out of 20
      cases with the peak concentration achieved between 1 and 12 h. Gel permeation
      chromatography showed only one major peak at the elution position of human ET-1
      standard both in the pre- and postoperative plasma. Thirteen patients showed
      transient hypoPTHaemia and hypocalcaemia which clearly coincided with the peak
      plasma ET-1 concentration in 12. However, there was no significant association
      between the extent of the increase in the plasma ET-1 levels and the incidence of
      the transient hypoparathyroidism. When blood was sampled at multiple sites during
      surgery, the plasma ET-1 concentrations tended to be higher in the internal
      jugular vein on the side of the preserved thyroid lobe (4.92 +/- 2.21 pg/ml) as
      well as on the side of the lobectomy (4.36 +/- 1.95) compared with that in the
      antecubital vein (3.66 +/- 1.44). Furthermore, tissue extracts from the
      parathyroid and thyroid contained considerably greater amounts of immunoreactive
      (ir-) ET-1 than most of the other tissues tested.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7829998
TI  - Influence of tumour necrosis factor-alpha, tumour necrosis factor-beta and
      interferon-gamma, separately and added together with interleukin-1 beta, on the
      function of cultured human thyroid cells.
AB  - Interleukin (IL)-1, tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma
      have been demonstrated in thyroid tissue. We have previously shown that high
      concentrations of IL-1 inhibit and low concentrations stimulate human thyroid
      cell function in vitro. In the present study, TNF-alpha, TNF-beta and IFN-gamma
      all inhibited thyroglobulin (Tg) and cAMP production from cultured human thyroid
      cells. When TNF-alpha was added simultaneously with IL-1 beta, the highest
      concentration of TNF-alpha (10(6) U/l) enhanced the inhibition of Tg and cAMP
      induced by IL-1 beta (1-10(5) U/l). TNF-beta had no influence on IL-1 beta
      induced inhibition. IFN-gamma (10(4) U/l) added together with IL-1 beta in lower
      concentrations (1-10(2) U/l) stimulated cAMP production, while at high
      concentrations of IL-1 beta (10(5) U/l), IFN-gamma enhanced the inhibitory
      influence of IL-1 beta on Tg production. The hormones of the immune system, IL-1,
      TNF and IFN-gamma, may thus contribute to the decreased thyroid function
      characteristic of some thyroid inflammatory diseases.

PMID- 7829999
TI  - Vitamin D metabolism in the Damara mole-rat is altered by exposure to sunlight
      yet mineral metabolism is unaffected.
AB  - Vitamin D may be endogenously synthesized in the skin in the presence of sunlight
      or, alternatively, acquired from dietary sources. Cryptomys damarensis appear to
      have a naturally impoverished vitamin D status with low plasma concentrations of
      both 25-hydroxyvitamin D (25(OH)D; < 5 ng/ml) and 1,25-dihydroxyvitamin D
      (1,25(OH)2D; < 20 pg/ml). We attribute this to their underground habitat and
      herbivorous habits. We questioned whether these subterranean mammals could
      utilize sunlight-mediated pathways and therefore compared vitamin D metabolism
      and function when animals were (a) housed naturally (control), (b) given an oral
      vitamin D3 (D3) supplement (1 IU/g dry matter food eaten per day) and (c) exposed
      to 10 h of sunlight. Control animals exhibited a highly efficient apparent
      fractional absorption of both calcium (Ca) and inorganic phosphorus (Pi) (> 90%),
      passive mode of intestinal mineral uptake, yet tightly regulated serum ionized
      calcium (Ca2+). The ratio of 25(OH)D-1 alpha-hydroxylase (1-OHase) to 25(OH)D-24R
      hydroxylase (24-OHase) activity in the kidney, corresponded with a state of
      vitamin D deficiency. Cryptomys damarensis responded to both oral D3
      supplementation and sun exposure by an increase in plasma concentration of
      1,25(OH)2D with a commensurate decline (P < 0.05) in 1-OHase activity, and a
      resulting decrease (P < 0.05) in the ratio of 1-OHase:24-OHase activity. Despite
      these changes, the intestinal mode of Ca uptake and plasma total Ca, Ca2+ and Pi
      remained unchanged with either treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7830000
TI  - Quantitative studies on the effect of prostacyclin on freshly isolated rat
      osteoclasts in culture.
AB  - Prostaglandins exert marked but transient inhibitory effects on bone resorption.
      The present study examines the effects of prostacyclin (0.15 to 25 microM) on the
      morphology of freshly disaggregated rat osteoclasts. An area descriptor, rho,
      represented changes in total cell spread area, and a motility descriptor, mu,
      represented overall changes in cell motility. The application of prostacyclin
      intercepted the trend of an increasing cell spread area with time and produced a
      transient reduction of rho, an R effect. Its magnitude depended upon
      concentration and was marked at 25 microM prostacyclin. The subsequent recovery
      (+0.8/min) of rho at this concentration resembled the persistent spreading seen
      in the absence of the agonist. There was also a sustained decrease in mu to
      approximately 60% of its pretreatment value (a Q effect) following the
      application of 25 microM prostacyclin. The extracellular application of 20 mM
      [Ca2+] produced a similarly transient cell retraction preceded by a rise of
      cytosolic [Ca2+], but without a corresponding decrease in mu. In contrast,
      prostacyclin did not elevate cytosolic [Ca2+], suggesting the triggering of an
      alternative transduction pathway. A fully reversible retraction together with
      incomplete quiescence may explain the transience characteristic of the
      antiresorptive action of prostacyclin.

PMID- 7830001
TI  - Differential regulation of prolactin receptor mRNA expression in rat liver and
      kidney by testosterone and oestradiol.
AB  - Prolactin (PRL) exerts a wide variety of physiological effects on mammalian
      tissues through its receptor (PRL-R) on the target cells. PRL-R in rat tissue
      consists of two isoforms, the long and the short form, and the regulatory
      mechanisms of their mRNA expression in tissues are complex and diverse. The
      present study reports the differential regulation of PRL-R mRNA expression in rat
      liver and kidney by testosterone and oestradiol. Using Northern blot analysis,
      short form PRL-R mRNA was clearly detected in female rat liver and male rat
      kidney, and long form PRL-R mRNA was faintly observed only in female rat liver.
      However, the reverse transcription-polymerase chain reaction method enabled
      efficient analysis of mRNA levels in short and long forms of PRL-R in the liver
      and kidney of both male and female rats. The mRNA levels for the long and short
      forms of PRL-R were depressed in the liver of male rats but not in that from
      female rats during sexual maturation. Castration of male rats resulted in the
      induction of the mRNAs for these two forms of PRL-R in the liver. Testosterone,
      but not oestradiol, completely blocked the induction by castration of liver PRL-R
      gene expression. In kidney, in contrast, mRNA levels for both forms of PRL-R were
      depressed in female rats but not in male rats after sexual maturation.
      Administration of oestradiol, but not of testosterone, caused marked repression
      of short form PRL-R mRNA, particularly in the kidney of male rats. The levels of
      long form PRL-R mRNA in the kidney was less affected by the administration of
      oestradiol. These results have suggested that the expression of PRL-R mRNAs in
      rat liver and kidney is differentially regulated by testosterone and oestrogen.

PMID- 7830003
TI  - 185th Meeting of the Society for Endocrinology with the Endocrine Section of the
      Royal Society of Medicine. London, 23-25 November 1994. Abstracts.

PMID- 7830002
TI  - Effects of acute and repeated intravenous administration of L-692,585, a novel
      non-peptidyl growth hormone secretagogue, on plasma growth hormone, IGF-1, ACTH,
      cortisol, prolactin, insulin, and thyroxine levels in beagles.
AB  - L-692,585 is a 2-hydroxypropyl derivative of L-692,429, both novel non-peptidyl
      growth hormone (GH) secretagogues. The effects of single and repeated intravenous
      administration of L-692,585 on serum or plasma GH and other hormones in beagles
      were evaluated. In a balanced 8-dog dose-ranging study, compared to the saline
      control with a mean (+/- S.E.M.) after-dose serum GH peak of 6.1 +/- 1.3 ng/ml, L
      692,585 significantly increased (P < 0.05) peak GH concentrations 4.3-fold (32.5
      +/- 7.0 ng/ml) at a dose of 0.005 mg/kg, 7-fold (49.4 +/- 10.6 ng/ml) at a dose
      of 0.02 mg/kg, and 21-fold (134.3 +/- 29.0 ng/ml) at a dose of 0.10 mg/kg. Total
      GH release, expressed as area under the curve, showed a similar dose-dependent
      increase. Peak GH levels were recorded at 5 or 15 min after dosing with the
      levels returning to near baseline by 90 min. Serum cortisol levels were increased
      above saline control levels in a dose-dependent manner; however, the increases
      were modest compared to the GH increases. Based on peak responses and total GH
      release, L-692,585 was 10- to 20-fold and 2- to 2.5-fold more potent than L
      692,429 and the growth hormone releasing peptide, GHRP-6, respectively. When L
      692,585 was administered once daily for 14 consecutive days at 0, 0.01 or 0.10
      mg/kg to each of 6 dogs, peak plasma GH levels and total GH release on days 1, 8
      and 15 significantly increased in a dose-dependent manner, and no desensitization
      was evident.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7830004
TI  - Quality of life for children and disabled children based on health as a resource
      concept.

PMID- 7830005
TI  - Disorders characterised by pain: a methodological review of population surveys.
AB  - OBJECTIVE--To review a series of conceptual and methodological problems
      encountered in surveys primarily devoted to pain disorders. CRITERIA FOR
      INCLUSION AND EXCLUSION OF ARTICLES--Published reports were systematically
      collected by electronic database searches (Medline), citations in existing
      publications, and through personal contacts. Relevant articles from clinical and
      epidemiological research on pain were included and special attention was given to
      epidemiological research on back pain. CONCLUSIONS--Surveys of pain disorders
      should be based on a multidimensional pain model that includes nociceptive input,
      pain perception, suffering, and pain behaviour as major components. Because of
      the limited applicability of diagnostic procedures or genuine "non-specificity"
      of pain states, or both, epidemiological surveys may result in a considerable
      proportion of cases without an identifiable pathophysiological basis. Staging and
      grading procedures for pain disorders (as distinguished from classification) may
      comprise various aspects of pain perception: regional distribution, pain
      intensity, temporal characteristics, sensory qualities, and dimensions of
      cognitive-emotional appraisal. Description of temporal development and
      chronification (staging) should refer to different components of the
      multidimensional pain model. Explicit a posteriori procedures for grading are
      preferable to implicit grading based on question wording. Evidence from several
      sources suggests that localistic concepts of pain may be misleading.
      Identification of complex pain syndromes should be one primary target for
      epidemiological pain surveys. Of the many factors that may impair the reliability
      and validity of data collected in pain surveys, recall biases seem to deserve
      special attention.

PMID- 7830006
TI  - Asymptomatic hyperglycaemia and major ischaemic heart disease events in Britain.
AB  - OBJECTIVE: To examine the association between non-fasting serum glucose
      concentrations and major ischaemic heart disease (IHD) events (fatal and non
      fatal myocardial infarction). DESIGN: A prospective study. SUBJECTS: A population
      based sample of 7735 middle aged British men. Known diabetics, men with a glucose
      concentration > or = 11.1 mmol/l at screening, and hypertensive patients taking
      regular medication were excluded from the analysis. With exclusions (n = 509) and
      missing glucose values (n = 49), there were 7177 men available for analysis. MAIN
      OUTCOME MEASURES: Major IHD events (fatal and non-fatal myocardial infarction)
      during 9.5 years follow up on all men. RESULTS: There were 505 major IHD events,
      222 fatal and 283 non-fatal, in the 7177 men studied. There was a non-linear
      relation between the glucose concentration and the risk (per 1000 men per year)
      of all major IHD events and fatal IHD events, with the excess risk in the upper
      quintile of the glucose distribution (> or = 6.1 mmol/l). The unadjusted relative
      risks (RR) in the upper glucose concentration quintile compared with the first to
      the fourth quintiles combined were 1.4 (95% CI 1.1, 1.7) for all events and 1.3
      (95% CI 1.0, 1.7) for fatal events. Adjustment for age, smoking, occupational
      status, body mass index, physical activity, systolic blood pressure, total and
      high density lipoprotein cholesterol, and triglyceride concentrations had a
      minimal effect on these relative risk estimates. This non-linear relationship
      between the serum glucose concentration and the risk of a major IHD event was
      observed in men with no evidence of IHD at screening (n = 5518) but not in men
      with IHD (n = 1659). In the former group, the RR (adjusted for major coronary
      risk factors) for all major IHD events in the upper quintile relative to the
      lower quintiles combined was 1.5 (95% CI 1.2, 2.0) and for fatal IHD events was
      1.8 (95% CI 1.1, 2.6). CONCLUSION: These data suggest that asymptomatic
      hyperglycaemia is an independent risk factor for major IHD events.

PMID- 7830007
TI  - Fat intake: implications of changes in distribution for setting dietary goals in
      the UK.
AB  - STUDY OBJECTIVE: To examine (a) changes in the shape of the distribution of
      dietary fat intake as the mean dietary fat intake of the population shifts and
      (b) implications for setting national dietary goals. DESIGN: Data on the
      percentage of energy from total fat, saturates, monounsaturates, polyunsaturates,
      and the P:S ratio were analysed for two dietary intervention trials and six cross
      sectional dietary surveys. The nutrient distributions from each study were
      described in terms of the mean, standard deviation (SD), coefficient of variation
      (CV), and skewness statistic. For the intervention trials statistical parameters
      were compared for groups who received and did not receive dietary advice. For the
      cross sectional studies, statistical parameters were compared across groups with
      different levels of mean fat intake. The implications of the results for setting
      dietary goals were considered using statistical models. MAIN RESULTS: For most
      fat fractions there was a positive association between the mean and the SD, and
      an inverse association between the mean and the CV, indicating that as the mean
      shifts upwards the SD increases but not in proportion to the mean. This is
      intermediate between a constant SD and a constant CV model. For a population
      nutrient goal of a maximum of 15% saturates, the estimated population mean for
      British women would be 8.4% using the constant SD model and 10.8% using the
      constant CV model. For saturates and the P:S ratio, a lower mean intake was
      associated with a greater positive skew in the distribution of reported intakes.
      For saturates, this is consistent with a group of high fat consumers who fail to
      reduce their intake as the population mean shifts downwards: a "rearguard
      effect". Findings for the P:S ratio are consistent with a group of consumers who
      produced a strong positive skew at low mean intakes, which reduced in size as the
      mean population intake increases: a "vanguard effect". CONCLUSIONS: These
      findings provide evidence that the distribution of fat intake may change with the
      mean to a degree that the setting and monitoring of nutritional goals may need to
      take account of changes in variance and shape of the intake distribution.

PMID- 7830008
TI  - Antioxidant vitamins in the diet: relationships with other personal
      characteristics in Finland.
AB  - STUDY OBJECTIVE: The study aimed to reveal associations between dietary
      antioxidant vitamins and other personal characteristics. DESIGN: Population
      based, cross sectional survey. SETTING: Twenty seven rural, industrial, and
      semiurban communities in six different regions of Finland. PARTICIPANTS: Subjects
      included 5304 men and 4750 women aged 15 years or older, who were interviewed
      about their dietary habits at the baseline study of the Finnish Mobile Clinic
      Health Examination Survey, 1967-72. MAIN RESULTS: Intakes of carotenoids and
      vitamins A, E, and C were estimated from dietary history interviews covering the
      subjects' food consumption in the preceding year. In older age groups intakes of
      all the vitamins studied were low. Occupation had a profound effect on dietary
      antioxidant vitamins: intakes were highest in white collar workers and lowest in
      farmers; those classified as service workers, industrial workers, or housewives
      came in between. Current smoking was inversely associated with dietary
      carotenoids and vitamin C, especially in men. The vitamin intakes of ex-smokers
      were equal to or even slightly higher than those of never smokers. Married men
      had higher intakes of carotenoids and vitamin C than men living alone. Body mass
      index was not an important determinant of the intake of antioxidant vitamins.
      CONCLUSIONS: The associations of dietary antioxidant vitamins with
      sociodemographic characteristics and smoking were strong enough to exert a
      confounding or modifying effect in studies on diet and diseases.

PMID- 7830009
TI  - Damp housing and adult health: results from a lifestyle study in Worcester,
      England.
AB  - STUDY OBJECTIVE: To explore the relationship between damp housing and adult
      health using two separate measures of ill health and taking into account the
      confounding effects of health related lifestyles and social factors. DESIGN AND
      SETTING: Analysis of responses gathered in a cross sectional, postal
      questionnaire survey of a randomly selected sample of 5347 residents of
      Worcester. PARTICIPANTS: Altogether 2353 people aged 16 to 64 years responded to
      the survey (adjusted response 52%). RESULTS: Nine per cent of respondents lived
      in housing which they reported to be damp. Rates were highest among young women.
      People who lived in damp housing were more likely to report long standing
      illness, disability, or infirmity; the increased prevalence could not be
      attributed to any particular medical condition. Perceived ill health, as measured
      by the sleep, energy, and social isolation dimensions of the Nottingham Health
      Profile, was also more common in this group. These associations could not be
      explained by lifestyle factors; the relationship proved strongest among people in
      non-manual social classes living in owner occupied housing. The prevalence of ill
      health increased as the severity of dampness increased. CONCLUSION: Self reported
      damp housing and ill health in adults were strongly associated, most noticeably
      among people in non-manual social classes living in owner occupied housing. The
      association met many of the epidemiological criteria necessary for suggesting
      causality: alternative explanations are discussed.

PMID- 7830010
TI  - Hazardous chemicals: psychological dimensions of the health sequelae of a
      community exposure in Texas.
AB  - STUDY OBJECTIVE: A chemical spill from an oil refinery exposed the local
      community to more than 40,000 lb of highly toxic and corrosive hydrofluoric acid.
      A community based symptom prevalence study found an association between exposure
      and physical symptoms: the psychological impact of the disaster and its potential
      effect on the reporting of physical symptoms is examined here. DESIGN: The study
      used a population based survey design consisting of two phases: phase I, the
      exposure phase, and, phase II, the symptom prevalence phase. SUBJECTS: In phase
      I, information indicative of exposure was collected on 10,811 individuals in a
      door to door survey of a geographically defined area. In phase II, symptom
      prevalence information was gathered through in-person interviews with 2509
      subjects selected from the phase I census in a sampling scheme that balanced
      across the exposure categories with regard to age, gender, and predisposition.
      The refusal rate in both phases was < 5%. MEASUREMENT AND MAIN RESULTS: Stepwise
      logistic regression analyses were used to assess the relative predictive
      importance of psychological variables and hydrofluoric acid exposure in
      explaining the reported physical symptoms two years after the disaster. The
      findings show a linear relationship between the level of hydrofluoric acid
      exposure and the degree of psychological stress two years after the accident.
      High exposure had a long term (more than two years) impact on physical health for
      some self reported symptoms, even after controlling for the psychological impact.
      Some physical symptom reports, however, were better explained by psychological
      status than by exposure to hydrofluoric acid. The physical symptoms for which
      exposure was the major predictor were those for which the biological plausibility
      of a relationship with hydrofluoric acid exposure was direct. CONCLUSIONS:
      Measures of psychological status should be included in symptom studies of health
      sequelae to man-made disasters so that the physical effects of exposure can be
      more accurately assessed.

PMID- 7830011
TI  - Urinary symptoms: prevalence and severity in British men aged 55 and over.
AB  - OBJECTIVE: To measure the prevalence and severity of urinary symptoms among men
      aged 55 and over in the British population. DESIGN: Cross sectional population
      survey using a postal questionnaire. SETTING: North West Thames health region.
      SUBJECTS: 1480 men aged 55 years and over randomly selected from 8 general
      practices. MAIN OUTCOME MEASURES: Self reported frequency and severity of urinary
      symptoms, their bothersomeness and previous prostate surgery. RESULTS: The
      response rate among eligible subjects was 78%. The prevalence of moderate and
      severe symptoms was 204 per 1000, rising from 160 per 1000 in the 55-59 age group
      to 259 per 1000 in the 70-74 age group and declining after the age of 80 to 119
      per thousand in the 85+ age group. Twelve per cent of men reported previous
      prostate surgery, and the probability of having had surgery increases steadily
      with age. About a third of those undergoing surgery have recurrence or
      persistence of symptoms after surgery. Of men with moderate and severe symptoms,
      27.9% reported that their symptoms were a medium or big problem, 36.9% reported
      that their symptoms interfered with their daily activities at least some of the
      time, and 43.1% were unhappy or 'felt terrible' about the prospect of a future
      with their current symptoms. CONCLUSION: The prevalence of urinary symptoms in
      men is lower than previously reported, although there is a substantial number of
      men who are bothered by, or who find their lives adversely effected by them.

PMID- 7830012
TI  - Primary infertility: characteristics of women in North America according to
      pathological findings.
AB  - STUDY OBJECTIVE: To determine, in women with primary infertility, whether
      specific characteristics or behavioural factors are associated with the various
      pathological conditions identified as contributing to the infertility. DESIGN:
      Case-control study. SETTING: Seven institutions in the USA or Canada.
      PARTICIPANTS: Study subjects were 1750 women who presented with primary
      infertility, among whom the main pathological cause of infertility was male
      factor (417), tubal obstruction (231), endometriosis (194), luteal phase defects
      (153), other ovulatory problems (193), cervical abnormalities (92), and
      polycystic ovarian disease (84) and 1765 control women who delivered their first
      child at the same institution. MAIN RESULTS: Except for tubal obstruction and
      polycystic ovarian disease, the characteristics and behaviours of the women with
      infertility did not differ appreciably according to the pathological conditions
      recorded. Women with tubal obstruction had had more sexual partners, an earlier
      age at first intercourse, were more likely to have used an intrauterine device
      but less likely to have used a condom, and were more likely to have smoked
      cigarettes and to have used various recreational drugs than the other women.
      Women with polycystic ovarian disease were more obese, had had fewer sexual
      partners, and were less likely to have used cigarettes, contraceptives, and
      recreational drugs than the other women. CONCLUSIONS: Sexually transmitted
      infections seem to increase the risk of tubal obstruction but not other causes of
      infertility. Obesity is associated with polycystic ovarian disease. These data
      offer few clues to the aetiology of infertility attributed to endometriosis,
      cervical abnormalities, luteal phase defects, other ovulatory defects, or to male
      factors.

PMID- 7830013
TI  - HIV infection: social network, social support, and CD4 lymphocyte values in
      infected homosexual men in Malmo, Sweden.
AB  - STUDY OBJECTIVE: The aim was to determine if there is an association between
      social network and social support and the CD4 cell count in HIV infected
      homosexual men. DESIGN: The study was cross sectional. A structured questionnaire
      assessing psychosocial factors such as social network and social support was
      administered at interview. Information on CD4 cell counts and HIV symptoms were
      obtained from participants' medical records. SETTING: The study population
      consisted of all HIV seropositive homosexual and bisexual men who had not been
      diagnosed as having AIDS seen at the Department of Infectious Diseases, the only
      hospital clinic in the city of Malmo (230,000 inhabitants), Sweden that provides
      care for HIV infected patients. PARTICIPANTS: Altogether 47 (68%) of 69 men in
      the population agreed to be interviewed. MAIN RESULTS: A low CD4 cell count was
      found more frequently in men with low social participation scores (OR 3.3; 95% CI
      1.0, 11), in those with a low adequacy of social participation (OR 3.8; 95% CI
      1.1, 13), and in men with low material support scores (OR 3.9; 95% CI 1.1, 13).
      After adjustment for age and time of awareness of the HIV infection, the two
      former associations remained statistically significant. CONCLUSIONS: These
      results, if reproduced in a longitudinal study, might suggest that psychosocial
      factors can affect an individual's immune system.

PMID- 7830014
TI  - Cervical screening: the optimum visit plan for contacting users and non-users in
      Scotland.
AB  - OBJECTIVE: To investigate the numbers of visits required to obtain interviews
      with users and non-users of cervical screening, and to determine the workload
      involved to enable an optimum visit plan to be developed. DESIGN: Case-control
      study of users and non-users of cervical screening using a flexible visit plan
      that involved up to eight attempts at contact. Visits were made in mornings,
      afternoons, and evenings, the visit pattern being determined by information
      gained from local sources. PATIENTS: Altogether 660 non-users of cervical
      screening (cases), aged 20-64 and registered with 23 randomly selected general
      practitioners (GPs), were identified from the Tayside computerised register of
      cervical smears. These women were selected from the computerised lists of 18 GPs
      in Dundee and five in Perth. A total of 417 women recorded as having a smear
      within the previous three years (controls), matched by age and GP, were also
      identified from the computerised register. RESULTS: Altogether 1834 attempts were
      made to contact the cases, of whom 339 were interviewed, giving a workload of 18
      interviews per 100 attempts. For the controls 1359 attempts were made at contact
      to yield 339 interviews, a workload of 25 interviews per 100 attempts. Refusals
      (19%) and incorrect addresses (23%) were the two major reasons for failing to
      achieve interview. Only for four (0.6%) of the cases and one (0.2%) of the
      controls was no information gained. The proportion of attempts which led to
      interview remained constant with increasing numbers of call-backs (up to six for
      the cases and eight for the controls). CONCLUSIONS: A flexible approach to visit
      scheduling that takes account of local knowledge can lead to interviews with 66%
      of non-users of health screening, when incorrect addresses are removed. It is
      preferable to plan for many (up to six) visits to achieve interview. This will
      minimise non-response bias without increasing the workload per successful
      interview.

PMID- 7830015
TI  - Geographical variation in hospital admission rates: an analysis of workload in
      the Oxford region, England.
AB  - OBJECTIVE: To measure variation in hospital admission rates between health
      districts in part of the English NHS, comparing a wide range of medical and
      surgical conditions. DESIGN: Retrospective analysis of interdistrict variation
      using linked routine hospital admission data. Comparisons were also made with
      levels of variation reported from the USA. SETTING: Oxford Regional Health
      Authority, 1979-86. SUBJECTS: Six district health authorities--total study
      population 2.1 million people, 1.6 million hospital admissions. MAIN MEASURES:
      Age and sex standardised hospital admission rates for resident populations for
      individual operations and diagnoses; systematic components of variation (SCV).
      RESULTS: Of 118 standard operation groups, 38 (26% of surgical workload) showed
      high variation (SCV 16 or more) and 40 (36% of surgical workload) showed low
      variation (SCV < 4). Operations (SCV) with very low levels of variation included
      prostatectomy (0.1), inguinal herniorraphy (0.9), and cholecystectomy (1.3).
      Rates were more variable for myringotomy (3.7), hysterectomy (4.3), dilatation
      and curettage (5.6), and tonsillectomy (6.2). The SCV was high for only four of
      the 40 commonest medical causes of admission, and was low for 18 of them.
      CONCLUSIONS: Most admissions in the Oxford region were for conditions that did
      not show a great deal of variation in admission rates. The level of variation for
      many surgical procedures was less than that reported in studies from the USA.
      Variation was no greater for medical causes of admission than for surgical
      conditions. Large scale variation may not be an inevitable consequence of
      autonomous clinical practice.

PMID- 7830016
TI  - Cancer incidence: life table risk versus cumulative risk.
AB  - STUDY OBJECTIVE: To study differences between various methods of estimating
      cancer risk in individuals. DESIGN: Information was obtained from a cancer
      registry. Lifetime risk was calculated using the life table method, taking
      competing causes of death into account and using well recognised methods such as
      the cumulative rate and risk. SETTING: Regional cancer registry of the
      Comprehensive Cancer Centre IKL, located in Maastricht, The Netherlands.
      PATIENTS: Patients with a first primary malignancy in 1989-90 in the catchment
      area of the cancer registry. MAIN RESULTS: The lifetime risk of developing cancer
      was estimated to be 34.8% for males and 30.4% for females. In males, especially,
      the risk estimates were considerably higher when the cumulative risk was used.
      CONCLUSIONS: The life table method is convenient for estimating the probability
      that a person will develop cancer during a defined period or during his or her
      lifetime. The other estimates overestimate the risk of the disease under
      investigation, especially in the very elderly.

PMID- 7830017
TI  - Leukaemia risk and social contact in children aged 0-4 years in southern England.

PMID- 7830018
TI  - Spread of influenza: a study of risk factors in homes for the elderly in Wales.

PMID- 7830019
TI  - Injury events: utility of self report in retrospective identification in the USA.

PMID- 7830020
TI  - Product definition for healthcare contracting.

PMID- 7830021
TI  - Cost-effectiveness: a new criterion for selecting therapy.

PMID- 7830022
TI  - Interventional neurovascular techniques in the treatment of stroke--state-of-the
      art therapy.
AB  - Interventional neurovascular techniques for the treatment of patients presenting
      with symptoms of acute or impending stroke, are now being utilized with
      increasing frequency in three major areas. (i) For patients presenting with
      cerebrovascular ischaemic symptoms due to haemodynamically significant stenosis
      from atherosclerosis, vasculitis, intimal hyperplasia, and dissection, cerebral
      percutaneous transluminal angioplasty has been shown to be beneficial for both
      extracranial and intracranial disease. (ii) Patients with acute, embolic
      occlusion of the internal carotid, middle cerebral, distal vertebral, and basilar
      arteries have been successfully treated by placement of microcatheters directly
      into the thrombus with successful thrombolysis, recanalization, and reperfusion
      to the distal ischemic brain. (iii) Acute arterial vasospasm secondary to
      subarachnoid haemorrhage is now being managed by balloon angioplasty in those
      instances where conventional medical therapy has failed. These techniques are
      altering our current management and broadening the therapeutic alternatives for
      patients who present with acute cerebrovascular insufficiency and stroke in
      evolution. As wider experience is gained in these techniques, the clinical
      indications for their use will also broaden.

PMID- 7830023
TI  - Nesidioblastosis in a young woman and the impact of hyperinsulinaemia on
      triglyceride metabolism.

PMID- 7830024
TI  - Is there a relationship between psoriasis and coeliac disease?

PMID- 7830025
TI  - The costs and effects of two different lipid intervention programmes in primary
      health care.
AB  - OBJECTIVE: To compare the costs and effects of two different intervention
      strategies for the nonpharmacological treatment of hypercholesterolaemia. DESIGN:
      Randomized, controlled trial. Subjects were randomly allocated to one of two
      intervention models and followed up for 1 year. SETTING: Varby Health Centre, a
      primary care practice located in a suburb of Stockholm. SUBJECTS: Subjects with a
      total serum cholesterol in the range 7.0-7.8 mmol L-1 and no signs of ischaemic
      heart disease or diabetes mellitus, randomized to a low-intensity (n = 35) or
      medium-intensity (n = 41) intervention. INTERVENTION: Two strategies were used,
      one labelled medium-intensity strategy which followed national current guidelines
      for nonpharmacological treatment of hypercholesterolaemia, the other was a low
      intensity strategy. MAIN OUTCOME MEASURES: Total serum cholesterol and
      intervention costs. RESULTS: Both intervention strategies resulted in small (mean
      3.5%) decreases in total cholesterol with no significant difference between the
      groups. The cost per subject in the low-intensity group was SEK 753 and in the
      medium-intensity group SEK 3614. CONCLUSIONS: Because the effect of the two
      intervention programmes did not differ, the low-intensity programme is to be
      preferred from a cost-effectiveness point of view. If only one-third of the
      population in Stockholm county with cholesterol levels > or = 6.5 mmol L-1 are
      discovered by the primary health care system, and follow the treatment advice,
      the net savings in the low-intensity model compared to the current guidelines
      here presented as the moderate-intensity model, would be SEK 93 million.

PMID- 7830026
TI  - The cost-effectiveness of a cardiovascular multiple-risk-factor intervention
      programme in treated hypertensive men.
AB  - OBJECTIVES: The aim of this study was to carry out a cost-effectiveness analysis
      of a multifactorial intervention programme in treated hypertensive patients.
      DESIGN: A cost-effectiveness analysis based on 3 years of follow-up in an open,
      randomized, parallel-group study with allocation either to a comprehensive,
      multiple-risk factor modification programme or to conventional treatment.
      SETTING: An outpatient clinic of a city hospital. SUBJECTS: Inclusion criteria
      were: male sex, age 50-72 (mean 66.4) years, treated hypertension and at least
      one of the following: serum cholesterol > or = 6.5 mmol L-1, and/or smoking
      and/or diabetes mellitus. A total of 508 patients were included in the study.
      INTERVENTIONS: Advice given to individuals, and group meetings based on
      nutritional advice and behavioural treatment principles. If necessary, drug
      therapy could be instituted to achieve the treatment goals in the intervention
      group: serum total cholesterol of < 6.0 mmol L-1, no smoking, HbAlc < 6.0% and
      diastolic blood pressure < 90 mmHg in both groups. MAIN OUTCOME MEASURE:
      Incremental cost per life-year gained of the intervention programme. RESULTS: The
      cost per life-year gained was SEK 4000 in an estimation based on the observed
      risk reduction and ranged between SEK 62,000 and SEK 163,000 in three estimations
      based on the risk factor changes. CONCLUSIONS: The analysis indicates that the
      intervention programme is cost-effective in the studied patient population.

PMID- 7830027
TI  - Endotoxaemia and inflammatory mediators in febrile patients with haematological
      disease.
AB  - OBJECTIVES: To study the pattern of plasma levels of endotoxin, tumour necrosis
      factor alpha (TNF-alpha), interleukin 6 (IL-6) and C-reactive protein (CRP) in
      febrile neutropenic patients and to assess the potential diagnostic value of
      these analyses. DESIGN: Consecutive prospective study. SETTING: Patients treated
      at the haematology ward at Danderyd Hospital, Sweden. SUBJECTS: Ninety-four
      patients with fever and haematological disease entered the study (male/female:
      59/35) with 176 febrile episodes. INTERVENTIONS: Blood samples were drawn at days
      0, 1, 2 and 6 after onset of fever for analysis of, endotoxin, TNF-alpha, IL-6
      and CRP. RESULTS: Infectious aetiology was established in 62.5% of the febrile
      episodes. Blood cultures showed significant growth in 71/176 (40.3%) febrile
      episodes. Nonbacteraemic bacterial infections were diagnosed in 34/176 (19.3%)
      episodes. Endotoxin was detected in plasma in 40% of febrile episodes regardless
      of aetiology. TNF-alpha was detected in 61% and IL-6 in 94% of all febrile
      episodes. The initial TNF-alpha and IL-6 levels were significantly higher in
      patients with Gram-negative bacteraemia than in patients with other causes of
      fever (P < 0.001). In episodes evaluated as successful after empirical antibiotic
      treatment, a significant (P < 0.001) decrease in CRP concentrations were found on
      day 6 after onset of fever. CONCLUSIONS: The sustained, low-grade endotoxaemia
      and persistently elevated levels of TNF-alpha and IL-6 found in febrile patients
      may reflect a failing mucosal barrier that allows endogenous bacterial products
      to reach the circulation. The diagnostic value of endotoxin, TNF-alpha, IL-6 and
      CRP to discriminate between bacteraemic and nonbacteraemic febrile episodes was
      very limited. The study supports the present policy of broad, empirical
      antibiotic treatment in patients with haematological disease and fever.

PMID- 7830028
TI  - Cardiovascular effects of prolonged growth hormone replacement in adults.
AB  - OBJECTIVES: To study the cardiovascular effects of human growth hormone (GH)
      replacement therapy in adults. INTERVENTION: Biosynthetic human GH given in a
      daily dose of 0.04 +/- 0.01 IU kg-1 for 6-18 months in an open trial. PATIENTS:
      Thirty-four GH-deficient hypopituitary patients on conventional replacement
      therapy, aged 19-67 years and with a body mass index of 18.0-410.0 kg/m2.
      MEASUREMENTS: Resting blood pressure, exercise tolerance, renal function and
      routine blood counts were assessed every 6 months. Two-dimensional
      echocardiography and Doppler ultrasound scanning were performed at 0, 6 and 12
      months of GH therapy. RESULTS: Exercise time increased significantly on GH from
      9.37 +/- 2.64 min at the start to 10.39 +/- 2.86 min (P < 0.001), 10.90 +/- 2.48
      min (P < 0.001) and 11.11 +/- 0.70 min (P < 0.001) at 6, 12 and 18 months
      respectively. There was no change in the heart rate or in the blood pressure at
      rest nor at the peak of exercise. No significant changes were observed in
      measures of cardiac structure (left ventricular mass index, left ventricular
      posterior wall thickness and interventricular septal thickness), ejection
      fraction nor in cardiac output. Isovolumic relaxation time, a marker of diastolic
      function, decreased in 24 patients after 6 months on GH (from 98.6 +/- 15.9 to
      89.6 +/- 15.2 ms; P < 0.03) but it was not different from baseline in the 18
      patients who were restudied at 12 months. There was no significant change in the
      left ventricular filling neither at 6 nor at 12 months. No significant, changes
      were observed in plasma electrolytes, creatinine nor in blood count on GH
      treatment. CONCLUSIONS: Growth hormone replacement therapy in hypopituitary
      adults for 6-18 months produced sustained increase in exercise tolerance but was
      not associated with changes in cardiac structure or systolic function.

PMID- 7830029
TI  - Heterozygous familial hypercholesterolaemia: the influence of the mutation type
      of the low-density-lipoprotein receptor gene and PvuII polymorphism of the normal
      allele on serum lipid levels and response to lovastatin treatment.
AB  - OBJECTIVES: To study whether (i) the low-density-lipoprotein (LDL)-receptor gene
      mutation type itself or (ii) the PvuII restriction-fragment-length polymorphism
      (RFLP) of the intact LDL-receptor gene affects serum lipid levels and their
      responses to lovastatin treatment in heterozygous familial hypercholesterolaemia
      (FH). DESIGN: Comparison of serum lipid levels in 149 heterozygous FH patients,
      including 79 patients with the FH Helsinki gene and 70 patients with the FH North
      Karelia gene, grouped according to the PvuII RFLP status of their nonmutated LDL
      receptor allele; studies of lovastatin responses in 23 FH patients with different
      mutation types. SUBJECTS: Molecularly defined heterozygous FH patients.
      INTERVENTIONS: DNA analysis by polymerase chain-reaction assay (PCR) and Southern
      blotting, fasting serum lipid measurements in all patients, and administration of
      lovastatin 40-80 mg daily to 16 FH Helsinki patients and seven FH North Karelia
      patients. MAIN OUTCOME MEASURES: Baseline and post-treatment serum cholesterol.
      LDL cholesterol, high-density-lipoprotein (HDL) cholesterol and triglyceride
      levels. RESULTS: There were no significant differences in serum total or LDL
      cholesterol levels in FH patients with the FH Helsinki gene compared with those
      carrying the FH North Karelia gene. Regardless of the mutation type, patients
      without the PvuII site in the normal LDL-receptor gene (P--subjects) tended to
      have 6-8% higher serum and LDL-cholesterol levels than patients possessing this
      restriction site (P+ subjects). Although not statistically significant, this
      difference is qualitatively and quantitatively similar to that reported in three
      different non-FH populations. Treatment with lovastatin brought about similar
      hypolipidaemic responses in FH patients with either mutation type (FH Helsinki or
      FH North Karelia) or PvuII RFLP status (P+ or P-). CONCLUSIONS: Two LDL-receptor
      gene mutations with dissimilar phenotypic characteristics are associated with
      similar serum lipid levels and response to statin treatment. Our data also
      support the previous assumption that the PvuII RFLP of the LDL-receptor gene
      locus is associated with variation of serum cholesterol levels.

PMID- 7830030
TI  - High serum alpha-tocopherol, albumin, selenium and cholesterol, and low mortality
      from coronary heart disease in northern Finland.
AB  - OBJECTIVES: The mortality from coronary heart disease (CHD) is exceptionally low
      in northernmost Finland, the Sami (formerly known as Lapp) area. To clarify the
      reasons for this, the levels of serum cholesterol, other classic risk factors,
      and major antioxidants, alpha-tocopherol, retinol, albumin and selenium were
      determined in males living in the low-mortality area and in a reference area.
      DESIGN: A health survey amongst reindeer herdsmen living in the three
      northernmost communes of Finland (the Sami area) and in the six neighbouring
      communities to the south (the reference area). The mortality from CHD in the two
      areas was determined from death certificates issued during the period 1981-1990.
      SUBJECTS: A total of 350 participants of the health survey, mean age 46 (SD 14)
      years. RESULTS: The mortality from CHD was 17% lower in the Sami area than in the
      reference area [95% confidence interval (CI) for the difference: 4-29]. Subjects
      living in the low-mortality area showed higher serum-lipid-adjusted alpha
      tocopherol (18.4 vs. 16.1 mumol L-1; 95% CI for difference: 0.7-3.9; P < 0.001),
      albumin (46.9 vs. 46.2 g L-1; 0.2-1.3; P < 0.02), selenium (1.59 vs. 1.47 mumol L
      1; 0.02-0.22; P < 0.02), cholesterol (6.76 vs. 6.34 mmol L-1; 0.12-0.72; P <
      0.001) and LDL cholesterol (4.76 vs. 4.45 mmol L-1; 0.05-0.57; P < 0.02) than
      those in the reference area. The HDL cholesterol:cholesterol ratio was lower in
      the Sami area than in the reference area (0.20 vs. 0.21; -0.02-0.00; P < 0.04).
      The Samis showed higher serum selenium than the Finns. Serum alpha-tocopherol
      increased with the consumption of reindeer meat and serum selenium increased with
      fish consumption. CONCLUSIONS: Alpha-tocopherol, albumin and selenium may play a
      role in the low mortality from CHD observed in northernmost Finland. The
      favourable serum antioxidant status in northerners may be credited to the local
      diet.

PMID- 7830031
TI  - Plasma cholesteryl ester transfer protein and high-density lipoproteins: new
      insights from molecular genetic studies.
AB  - Recent studies in transgenic mice provide strong evidence for a direct anti
      atherogenic role of high-density lipoproteins (HDL) and highlight the importance
      of multiple gene interactions in the regulation of HDL levels. Plasma lipid
      transfer processes mediated by cholesteryl ester transfer protein (CETP) have a
      major impact on HDL levels, as revealed in studies of human genetic CETP
      deficiency and CETP transgenic mice. Subsequent to the discovery of an intron 14
      CETP gene splicing defect, several new CETP gene mutations have been discovered
      recently in Japanese and other populations. One of these is an exon 15 missense
      mutation, changing amino acid 442 of CETP from aspartate to glycine. Population
      studies in Japan indicate that CETP gene mutations are sufficiently common to
      have a significant influence on HDL levels in the general population. Studies in
      transgenic mice show that CETP expression results in decreased levels of HDL
      cholesterol, but that the effects of CETP on HDL apolipoprotein A-I (apoA-I)
      content and size show important modulation by co-expression with transgenes
      encoding human apoA-I, apoC-III and apoA-II. In addition to the apparent
      antiatherogenic phenotype of human genetic CETP deficiency, high level expression
      of CETP in transgenic mice leads to accelerated atherosclerosis, illustrating the
      pro-atherogenic potential of CETP expression.

PMID- 7830032
TI  - Coffee consumption and risk of ischaemic heart disease--a settled issue?
AB  - OBJECTIVE: Based on a meta-analysis, it was recently stated that there is no
      association between coffee consumption and the risk of coronary heart disease.
      Why then, have studies on the issue shown quite variable results? DESIGN SETTING
      AND SUBJECTS: A prospective study was performed in the Copenhagen Male Study on
      2975 men (53-74 years) without cardiovascular disease at baseline in 1985/1986.
      They were classified according to self-reported consumption of filter coffee.
      Some 147 men (5%) were coffee abstainers. Potential confounders were alcohol use,
      physical activity, smoking, serum cotinine, serum lipids, serum selenium, body
      mass index, blood pressure, Lewis blood group, hypertension, non-insulin
      dependent diabetes mellitus and social class. MAIN OUTCOME MEASURES: The
      incidence of ischaemic heart disease (IHD) 1985/86-1991. RESULTS: Some 184 men
      had a first IHD event. There was no significant difference between those
      consuming 1-4, 5-8 or > or = 9 cups per day after controlling for confounders (P
      value of trend test: 0.14). The crude incidence rates were 6.8, 6.7 and 4.6%,
      respectively; the adjusted rates were 6.8, 6.7 and 4.0%, respectively. Coffee
      consumption was significantly (P < 0.05) inversely correlated with serum selenium
      concentration (never previously described) and, positively or negatively, with a
      number of other potential risk factors: smoking, alcohol use, serum
      triglycerides, serum cholesterol, blood pressure, social class, body mass index,
      and serum selenium. In nonsmokers and smokers of only a small amount of tobacco,
      coffee consumption was associated with a lower risk of IHD (P < 0.05).
      CONCLUSION: We conclude that the association between coffee consumption and risk
      of IHD is conditioned by known risk factors correlated with use of coffee, which
      may partly explain the inconsistencies in the results of previous studies.

PMID- 7830033
TI  - Contrasting effects of angiotensin converting inhibitor and alpha-1-antagonist on
      albuminuria in insulin-dependent diabetes mellitus patients with nephropathy.
AB  - OBJECTIVE: The main aim of this study was to examine the effects of an
      angiotensin converting inhibitor, enalapril, and an alpha-1 (alpha-1) antagonist,
      doxazosin, on albumin excretion, renal haemodynamics and tubular function in
      insulin-dependent diabetes mellitus patients with nephropathy. DESIGN: The study
      consisted of a four-week run-in period, a four-week active treatment period, a
      four-week wash-out period and a second four-week active treatment period.
      SETTING: The study was performed in the out-patient clinic at a university
      hospital. SUBJECTS: Ten patients with insulin dependent diabetes mellitus with
      macroalbuminuria (> 200 micrograms min-1), mild to moderate hypertension
      (diastolic blood pressure 85-115 mmHg) and serum creatinine level below 200 mumol
      L-1 were included in the study. MAIN OUTCOME MEASURES: The effect of the drugs on
      albumin and total protein excretion, beta-2-microglobulin, proximal tubular
      enzyme markers and renal haemodynamics. RESULTS: Systolic and diastolic blood
      pressure were equally reduced by both drugs. Enalapril reduced albumin excretion
      from 1090 +/- 281 micrograms min-1 to 742 +/- 246 micrograms min-1 (P < 0.01) and
      total protein excretion from 2.0 +/- 0.4 g per 24 h to 1.3 +/- 0.4 per 24 h
      whereas doxazosin was without effect. Glomerular filtration rate and effective
      renal plasma flow were unchanged by either drug. Doxazosin increased filtration
      fraction from 0.21 +/- 0.02 to 0.23 +/- 0.01 (P < 0.05). The urinary excretion of
      the proximal enzyme markers N-acetyl-beta-glucosaminidase and alkaline
      phosphatase were elevated as well as urinary excretion of beta-2-microglobulin.
      However, neither the excretion of beta-2-microglobulin nor the enzyme markers
      were affected by either drug. CONCLUSIONS: Enalapril, but not doxazosin, reduces
      albuminuria in insulin dependent diabetes mellitus patients with nephropathy. The
      drugs exert differential effects on renal haemodynamics.

PMID- 7830034
TI  - Stroke therapy--time for a clinical breakthrough: introduction.

PMID- 7830035
TI  - Why do all drugs work in animals but none in stroke patients? 1. Drugs promoting
      cerebral blood flow.
AB  - Medical treatments which presumably alter cerebral blood flow (CBF) have been
      quite unimpressive in their effect on stroke outcome. In considering experimental
      and clinical data from the use of haemodilution and of the antiplatelet agent
      prostacyclin in focal cerebral ischaemia, and the current work with fibrinolytic
      agents in acute stroke, several lessons are apparent. Often agents hypothesized
      to affect CBF receive an underserved reputation based on sparse experimental
      evidence. Significant even unsuspected differences between species limit
      application to the clinical setting. Limitations of CBF measurements in
      experimental models and in humans raise questions about apparent responses to
      those agents. The failure to confirm a relationship between CBF enhancement and
      reduction in infarct development experimentally has plagued these approaches. The
      need for early application of agents which may modulate CBF during cerebral
      ischaemia is critical. Attention to these general issues and careful application
      of appropriate models are necessary so that a potentially useful therapeutic
      intervention is not overlooked.

PMID- 7830036
TI  - Why do all drugs work in animals but none in stroke patients? 2. Neuroprotective
      therapy.

PMID- 7830037
TI  - Thrombolysis in ischaemic stroke--how far from a clinical breakthrough?
AB  - Thromboembolic occlusions of the cerebral arteries often recanalize
      spontaneously, and patients with early recanalization have a better outcome than
      patients who do not recanalize. Clinical as well as experimental data support the
      concept of a time window within which brain tissue will profit from restoration
      of blood flow. In occlusion of middle cerebral artery, internal carotid artery,
      as well as vertebrobasilar arteries, open studies of intra-arterial
      administration of thrombolytic agents have demonstrated recanalization within
      hours in 40-100% of patients in small series. In intravenous drug administration,
      recanalization rate was obtained in 34-59% of patients. Favourable outcome was
      associated with recanalization. Intracerebral bleeding complications with
      clinical deterioration occurred in about 10% of patients. Three randomized
      controlled trials comprising 156 patients with acute ischaemic stroke have
      reported favourable outcome in treated patients, with no difference of
      intracerebral haemorrhagic complications between treated and controls. Results of
      ongoing randomized placebo controlled trials are expected in 1995 to disclose
      whether a clinical breakthrough is achieved or whether haemorrhagic complications
      will outweigh a beneficial effect of thrombolytic therapy in acute cerebral
      ischaemia.

PMID- 7830038
TI  - Retrovirus-mediated expression of an artificial beta-endorphin precursor in
      primary fibroblasts.
AB  - Peptides are of potential interest in the field of gene therapy but require
      modification by genetic engineering to facilitate their secretion. Amino terminal
      addition of a signal peptide is not always sufficient to achieve this goal, as
      found in this study for beta-endorphin. To overcome this problem, addition of the
      pre-pro-sequence of mouse nerve growth factor to beta-endorphin was tested.
      Retrovirus-mediated expression of a hybrid construct of the pre-pro-sequence of
      nerve growth factor and human beta-endorphin in primary fibroblasts resulted in
      the secretion of beta-endorphin immunoreactivity at a rate of 620 pg/h/10(6)
      cells. Analysis of the secreted beta-endorphin immunoreactivity with reverse
      phase HPLC, immunoassays using three different antibodies, and an assay for the
      specific displacement of [3H][D-Ala2,N-MePhe4,Gly-ol5]enkephalin from mu-opioid
      receptors suggests that the pre-pro-sequence is cleaved off from the pre-pro
      sequence/beta-endorphin construct prior to secretion, resulting in bona fide beta
      endorphin. Transplantation of beta-endorphin-secreting cells into brain or spinal
      cord may provide a gene therapy approach for the treatment of chronic, opioid
      sensitive pain states.

PMID- 7830039
TI  - Structural organization of the murine D3 dopamine receptor gene.
AB  - We have cloned the gene encoding the murine D3 dopamine receptor and have
      analyzed its intron-exon structural organization, to gain a better understanding
      of the detailed architecture of the D2 dopamine receptor genes. Restriction and
      sequence analysis reveal the presence of six introns, in contrast to the five
      introns previously reported for the rat D3 receptor. The extra intron is located
      in the receptor's putative third cytoplasmic loop and generates an intron-exon
      organization directly analogous to that found in the D2 receptor gene. In
      addition, we have sequenced the 5' and 3' nontranslated sequences flanking the
      coding region and have identified a putative poly(A) adenylation signal. These
      sequences are found to have a far lower homology with the corresponding rat
      nontranslated sequences than is found for the D2 receptor, suggesting that the
      control of D3 receptor expression may vary more between species than the control
      of D2 receptor expression.

PMID- 7830040
TI  - An HSV-1 vector expressing tyrosine hydroxylase causes production and release of
      L-dopa from cultured rat striatal cells.
AB  - In this report we demonstrate that a defective herpes simplex virus type one (HSV
      1) vector can express enzymatically active tyrosine hydroxylase in cultured
      striatal cells that are thereby converted into L-DOPA-producing cells. A human
      tyrosine hydroxylase cDNA (form II) was inserted into an HSV-1 vector (pHSVth)
      and packaged into virus particles using an HSV-1 strain 17 mutant in the
      immediate early 3 gene (either ts K or D30EBA) as helper virus. Cultured
      fibroblasts were infected with pHSVth and 1 day later tyrosine hydroxylase
      immunoreactivity and tyrosine hydroxylase enzyme activity were observed. The
      tyrosine hydroxylase enzyme activity directed the production of L-DOPA. pHSVth
      infection of striatal cells in dissociated cell culture resulted in expression of
      tyrosine hydroxylase RNA and tyrosine hydroxylase immunoreactivity. Release of L
      DOPA and low levels of dopamine were observed from cells in pHSVth-infected
      striatal cultures. Expression of tyrosine hydroxylase and release of
      catecholamines were maintained for at least 1 week after infection.

PMID- 7830041
TI  - Regulation of cytochrome c oxidase subunit mRNA and enzyme activity in rat brain
      reward regions during withdrawal from chronic cocaine.
AB  - A subtractive hybridization and differential screening procedure was used to
      detect up-regulation of cytochrome c oxidase (CO) subunits I, III, and IV mRNA in
      the nucleus accumbens (NAc) of rats chronically treated with cocaine. Northern
      blot analyses of mRNA isolated from individual rats confirmed that CO subunit I
      was up-regulated by chronic, but not acute, cocaine in two brain regions, the NAc
      (33%) and caudate-putamen (CP) (35%). CO activity, used as a measure of metabolic
      activity, was increased by 88% in the NAc, and decreased by 20% in the medial
      prefrontal cortex (mPFC), the day after chronic treatment was terminated. CO
      enzyme activity was not regulated in the CP, or in other brain regions not
      involved in drug reward. CO activity in both the NAc and mPFC showed unique time
      dependent patterns of regulation during the week after chronic cocaine treatment.

PMID- 7830042
TI  - Expression of biologically active basic fibroblast growth factor by genetically
      modified rat primary skin fibroblasts.
AB  - Basic fibroblast growth factor (FGF-2) is normally expressed as a cell-associated
      protein, and accordingly it is not clear how it exerts its action on target cells
      in vivo. It has been proposed that cells release, by death or other mechanisms,
      small amounts of FGF-2 that then acts in an autocrine manner. To address the
      question of whether it is necessary that FGF-2 remain cell associated or needs to
      be secreted from cells to have biological activity, we expressed the 18-kDa form
      of FGF-2 in primary fibroblasts as a cell-associated (FGF-2-B) or as a secreted
      (FGF-2-S) protein. FGF-2 protein is detected in cell lysates and membrane
      fractions of both cell types, whereas it is present in significant amounts only
      in the conditioned medium of FGF-2-S cells. No FGF-2 is detected in control
      (untransfected) cells. FGF-2-S cells also grow faster than the control of FGF-2-B
      cells. Yet, when evaluated for their ability to promote the survival of embryonic
      hippocampal neurons in vitro, both the cell types are active, establishing the
      activity of the transgene product. We conclude that FGF-2 is active when
      engineered to be expressed as a cell-associated form or secreted from cells.

PMID- 7830043
TI  - Analysis of the alternative promoters that regulate tissue-specific expression of
      human aromatic L-amino acid decarboxylase.
AB  - Previously we identified two alternative first exons (exon N1 and exon L1) coding
      for 5' untranslated regions of human aromatic L-amino acid decarboxylase (AADC)
      and found that their alternative usage produced two types of mRNAs in a tissue
      specific manner. To determine the cis-acting element regulating the tissue
      specific expression of human AADC, we produced three kinds of transgenic mice
      harboring 5' flanking regions of the human AADC gene fused to the bacterial
      chloramphenicol acetyltransferase (CAT) gene. The transgene termed ACA contained 
      7.0 kb to -30 bp in exon N1, including the entire exon L1; ACN contained -3.6 kb
      to -30 bp in exon N1; and ACL contained -2.8 kb to -42 bp in exon L1. The ACA
      transgenic mice expressed CAT at extremely high levels in peripheral nonneuronal
      tissues, such as pancreas, liver, kidney, small intestine, and colon, that
      contained endogenous high AADC activity, whereas CAT immunoreactivity was not
      detected in either catecholaminergic or serotonergic neurons in the CNS. Thus, it
      was suggested that the ACA transgene contained the major part of cis-regulatory
      elements for the expression of AADC in peripheral nonneuronal tissues. On the
      other hand, the ACN transgenic mice moderately expressed CAT in various tissues
      except for the lung and liver, and the ACL transgenic mice showed moderate CAT
      expression only in the kidney.

PMID- 7830044
TI  - Recombinant human NMDA homomeric NR1 receptors expressed in mammalian cells form
      a high-affinity glycine antagonist binding site.
AB  - The cDNA NYMDAR1 (NR1) encodes a single polypeptide that forms a receptor-channel
      complex with electrophsiological and pharmacological properties characteristic of
      the N-methyl-D-aspartate receptor. Homomeric NR1 recombinant receptors expressed
      in Xenopus oocytes show functional responses with low levels of conductance. In
      this study we have characterized, by radioligand binding techniques, the
      pharmacological properties of homomeric receptors of two human NR1 isoforms (NR1a
      and NR1e, which differ in their C-terminal region), transiently expressed in
      human embryonic kidney 293 cells. The glycine site antagonist (+/-)-4-(trans)-2
      carboxy-5,7-dichloro-4-[3H]phenylaminocarbonylamino - 1,2,3,4-tetrahydroquinoline
      ([3H]L-689,560) bound to NR1a- and NR1e-transfected cells with high affinity (KD
      = 3.29 and 1.61 nM, respectively). Bmax values for NR1a- and NR1e-transfected
      cells were 3.82 and 1.69 pmol/mg of protein, respectively, and Hill coefficients
      were close to unity. Ki values for glycine site antagonists inhibiting [3H]L
      689,560 binding to NR1e-transfected cells were similar to those observed with rat
      brain membranes. Affinity values for agonists and partial agonists were four-to
      16-fold weaker, indicating that the glycine site of homomeric NR1 receptors is in
      an antagonist-preferring state. Ki values obtained with NR1a-transfected cells
      were approximately twofold lower than those obtained with NR1e-transfected cells.
      High-affinity binding to NR1-transfected cells was not observed with the
      transmitter recognition site radioligands L-[3H]glutamate and D,L-(epsilon)-2
      [3H]amino-4-propyl-5-phosphono-3-pentanoic acid ([3H]CGP-39653) or the ion
      channel radioligand [3H]dizocilpine ([3H]MK-801).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7830045
TI  - Expression of mRNAs encoding subunits of the NMDA receptor in developing rat
      brain.
AB  - Developmental changes in the levels of N-methyl-D-aspartate (NMDA) receptor
      subunit mRNAs were identified in rat brain using solution hybridization/RNase
      protection assays. Pronounced increases in the levels of mRNAs encoding NR1 and
      NR2A were seen in the cerebral cortex, hippocampus, and cerebellum between
      postnatal days 7 and 20. In cortex and hippocampus, the expression of NR2B mRNA
      was high in neonatal rats and remained relatively constant over time. In
      contrast, in cerebellum, the level of NR2B mRNA was highest at postnatal day 1
      and declined to undetectable levels by postnatal day 28. NR2C mRNA was not
      detectable in cerebellum before postnatal day 11, after which it increased to
      reach adult levels by postnatal day 28. In cortex, the expression of NR2A and
      NR2B mRNAs corresponds to the previously described developmental profile of NMDA
      receptor subtypes having low and high affinities for ifenprodil, i.e., a delayed
      expression of NR2A correlating with the late expression of low-affinity
      ifenprodil sites. In cortex and hippocampus, the predominant splice variants of
      NR1 were those without the 5' insert and with or without both 3' inserts. In
      cerebellum, however, the major NR1 variants were those containing the 5' insert
      and lacking both 3' inserts. The results show that the expression of NR1 splice
      variants and NR2 subunits is differentially regulated in various brain regions
      during development. Changes in subunit expression are likely to underlie some of
      the changes in the functional and pharmacological properties of NMDA receptors
      that occur during development.

PMID- 7830046
TI  - K-252a induces tyrosine phosphorylation of the focal adhesion kinase and neurite
      outgrowth in human neuroblastoma SH-SY5Y cells.
AB  - The protein kinase inhibitor K-252a has been shown to promote cholinergic
      activity in cultures of rat spinal cord and neuronal survival in chick dorsal
      root ganglion cultures. To determine the mechanism by which K-252a acts as a
      neurotrophic factor, we examined the effects of this molecule on a human
      neuroblastoma cell line, SH-SY5Y. K-252a induced neurite outgrowth in a dose
      dependent manner. Coincident with neurite outgrowth was the early tyrosine
      phosphorylation of 125- and 140-kDa proteins. The phosphorylation events were
      independent of protein kinase C inhibition because down-regulation of protein
      kinase C by long-term treatment with phorbol ester did not prevent K252a-induced
      tyrosine phosphorylation. Similarly, the protein kinase C inhibitors H7, GF
      109203X, and calphostin C did not induce the phosphorylation. We have identified
      one of the phosphosubstrates as the pp125 focal adhesion protein tyrosine kinase
      (Fak). Induction of phosphorylation coincided with increased Fak activity and
      appeared to be independent of ligand/integrin interaction. The induction of Fak
      phosphorylation by K-252a was also observed in LA-N-5 cells and primary cultures
      of rat embryonic striatal cells but not in PC12 cells. The protein kinase C
      independent induction of tyrosine phosphorylation and the identification of Fak
      as a substrate of K-252a-induced tyrosine kinase activity suggest that this
      compound mediates neurotrophic effects through a novel signaling pathway.

PMID- 7830047
TI  - Nerve growth factor promotes neurite regeneration in PC12 cells by translational
      control.
AB  - When PC12 cells are primed with nerve growth factor (NGF) for periods of > or = 1
      week, they acquire the ability to regenerate neurites rapidly in response to NGF.
      It is not known how NGF promotes this regeneration, but it does not require
      ongoing RNA synthesis. Previous studies have suggested that NGF directs the
      accumulation of precursor molecules that are rapidly assembled to form the
      regenerated neurites. To address the nature of these precursor molecules, we have
      treated PC12 cells with macromolecular synthesis inhibitors during the priming
      and regeneration phases of neurite growth. Here we show that NGF promotes neurite
      regeneration by inducing the synthesis of new proteins. These proteins are
      encoded by short-lived mRNAs that are generated during the NGF priming period.
      The isolation and identification of these mRNAs will allow a further
      understanding of how NGF promotes neurite regeneration.

PMID- 7830048
TI  - Regulation of the expression of NMDA receptor subunits in rat cerebellar granule
      cells: effect of chronic K(+)-induced depolarization and NMDA exposure.
AB  - The influence of K(+)-induced membrane depolarization and NMDA treatment on the
      regulation of NMDA receptor subunit (NR) expression was investigated during the
      development of granule cells in culture, as a follow-up of previous work on NMDA
      receptor activity. In spite of the increase in NMDA receptor activity elicited by
      these treatments (K25 or K10 + NMDA cultures), the main developmental changes in
      receptor mRNA levels were similar to those in untreated cells (K10) (a threefold
      increase in total NMDA receptor mRNA, quantitative dominance of NR1 mRNA, late
      expression of NR2C, and virtual absence of NR2D. However, high K+ and NMDA
      treatment resulted in a greater increase of NR2A mRNA levels and a retardation in
      the developmental changes in the relative amounts of NR2B and NR2C mRNAs. The
      correspondence between NMDA receptor activity and the amount of NR1 and NR2A
      subunit proteins was excellent, the rank order being K25 > K10 + NMDA > K10 at 9
      days in vitro. Because the increase in subunit mRNA was not always paralleled by
      an increase in subunit protein, the control of NMDA receptor expression involves
      critically, in addition to gene transcription, regulation of translational and/or
      posttranslational events.

PMID- 7830049
TI  - PC12 cells overexpressing tissue plasminogen activator regenerate neurites to a
      greater extent and migrate faster than control cells in complex extracellular
      matrix.
AB  - PC12 cells were stably transfected with expression vectors containing rat tissue
      plasminogen activator (tPA) under control of either a cytomegalovirus or rous
      sarcoma virus promoter. Cell lines were characterized using protease assays,
      ELISAs, immunoblots, northern blots, and Southern blots. Control PC12 cells or
      cells containing vectors alone released about 1 pg tPA/cell/24 h, whereas cells
      stably transfected with a tPA cDNA released 2-5 pg tPA/cell/24 h. A strong
      correlation existed between the amount of tPA released and the ability of cells
      to degrade extracellular matrix. Experiments with protease inhibitors and
      antibodies against tPA and plasminogen indicated that degradation of matrix
      involved tPA-generated plasmin and that the amount of matrix degraded was
      dependent on the amount of tPA released. Cells expressing high levels of tPA
      migrated on a three-dimensional matrix about twice as fast as control cells and
      regenerated neurites within three-dimensional gels of Matrigel to a greater
      extent than control cells. Antibodies that inhibited tPA and plasminogen
      decreased migration and neurite regeneration, indicating that tPA was involved in
      both events, PC12 cells overexpressing tPA should provide a useful model system
      for investigating neural functions of tPA including its role in migration and
      regeneration.

PMID- 7830050
TI  - L-dopa inhibits complex IV of the electron transport chain in catecholamine-rich
      human neuroblastoma NB69 cells.
AB  - L-3,4-Dihydroxyphenylalanine (L-dopa) is toxic for human neuroblastoma cells NB69
      and its toxicity is related to several mechanisms including quinone formation and
      enhanced production of free radicals related to the metabolism of dopamine via
      monoamine oxidase type B. We studied the effect of L-DOPA on activities of enzyme
      complexes in the electron transport chain (ETC) in homogenate preparations from
      the human neuroblastoma cell line NB69. As a preliminary step we compared the
      activity of ETC in cellular homogenates with that of purified mitochondria from
      NB69 cells and rat brain. Specific activities for complex I, complex II-III, and
      complex IV in NB69 cells were, respectively, 65, 96, and 32% of those in brain
      mitochondria. Complex I activity was inhibited in a dose-dependent way by 1
      methyl-4-phenylpyridinium ion with an EC50 of approximately 150 microM. Treatment
      with 0.25 mM L-dopa for 5 days reduces complex IV activity to 74% of control
      values but does not change either complex I or citrate synthase. Ascorbic acid (1
      mM), which protects NB69 cells from L-dopa-induced neurotoxicity, increases
      complex IV activity to 133% of the control and does not change other ETC
      complexes. Ascorbic acid also reverses L-dopa-induced reduction of complex IV
      activity in NB69 cells. This observation might indicate that the protection
      observed with ascorbic acid is related to complex IV activation. In vitro
      incubation with L-dopa (0.125-4 mM) for 2 min produced a dose-dependent reduction
      of complex IV without change in complex I and II-III activities.

PMID- 7830051
TI  - Thrombin receptor activation stimulates astrocyte proliferation and reversal of
      stellation by distinct pathways: involvement of tyrosine phosphorylation.
AB  - Treatment of cultured type-1 astrocytes with thrombin leads to cell proliferation
      and reversal of stellation. The half-maximal concentrations of thrombin required
      for each response are 500 and 2 pM, respectively. To test whether they might be
      mediated by different receptors, we examined the contribution of the G protein
      coupled thrombin receptor to these responses in purified rat astrocytes by using
      the agonist peptide SFLLRNP. In the absence of added growth factors, SFLLRNP
      fully mimicked the effects of thrombin at half-maximal concentrations of 30
      microM for an increase in cell number and DNA synthesis and 100 nM for the
      reversal of stellation. The role of protein tyrosine phosphorylation in these
      events was investigated using antiphosphotyrosine antibodies. Thrombin and
      SFLLRNP at concentrations at least 10-fold greater than those required for half
      maximal reversal of stellation but below those required for mitogenesis induced
      an identical pattern of tyrosine phosphorylation on several proteins of 55-65,
      106, 110-115, and 120-130 kDa. The response was rapid (< 1 min) and transient
      with a peak response after approximately 2 min. The specific tyrosine kinase
      inhibitor herbimycin A did not affect thrombin- or SFLLRNP-mediated reversal of
      stellation at concentrations of up to 1 microM. In contrast, 1 microM herbimycin
      fully inhibited the ability of thrombin and SFLLRNP to increase cell number and
      stimulate DNA synthesis. Furthermore, this inhibition by 1 microM herbimycin A
      corresponded to inhibition of receptor-induced tyrosine phosphorylation. Thus,
      cell proliferation but not reversal of stellation is dependent on thrombin
      receptor-activated tyrosine kinase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7830052
TI  - Metabotropic glutamate receptor (mGluR)-mediated potentiation of cyclic AMP
      responses does not require phosphoinositide hydrolysis: mediation by a group II
      like mGluR.
AB  - Metabotropic glutamate receptors (mGluRs) in the CNS are coupled to a variety of
      second messenger systems, the best characterized of which is activation of
      phosphoinositide hydrolysis. Recently, we found that activation of mGluRs in rat
      brain slices by the selective mGluR agonist 1-aminocyclopentane-1S,3R
      dicarboxylic acid (1S,3R-ACPD) potentiates cyclic AMP (cAMP) responses elicited
      by activation of other receptors coupled to Gs. It has been suggested that mGluR
      mediated potentiation of cAMP responses is secondary to activation of
      phosphoinositide hydrolysis. However, preliminary evidence suggests that this is
      not the case. Therefore, we designed a series of experiments to test more fully
      the hypothesis that mGluR-mediated potentiation of cAMP responses is secondary to
      phosphoinositide hydrolysis. Inhibitors of both protein kinase C and
      intracellular calcium mobilization failed to antagonize 1S,3R-ACPD-stimulated
      potentiation of cAMP responses. Further, coapplication of phorbol esters and
      1S,3R-ACPD induced a cAMP response that was greater than additive. Finally, (RS)
      3,5-dihydroxyphenylglycine, a selective agonist of mGluRs coupled to
      phosphoinositide hydrolysis, failed to potentiate cAMP responses, whereas
      (2S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine, an mGluR agonist that does
      not activate mGluRs coupled to phosphoinositide hydrolysis, elicited a robust
      potentiation of cAMP responses. In total, these data strongly suggest that mGluR
      mediated potentiation of cAMP responses is not secondary to activation of
      phosphoinositide hydrolysis and is likely mediated by a group II mGluR.

PMID- 7830053
TI  - Cyclic AMP-dependent modulation of vesicular monoamine transport in
      pheochromocytoma cells.
AB  - Cyclic AMP (cAMP) is well known to enhance tyrosine hydroxylase activity in PC12
      cells. We were able to demonstrate, however, that the cellular dopamine level in
      PC12 was lowered by dibutyryl cAMP. Furthermore, the decrease in the cellular
      level of dopamine was accompanied by about a 10-fold increase in the medium. The
      aim of this work was to elucidate the effect of cAMP on catecholamine transport.
      Dibutyryl cAMP did not induce exocytotic release of norepinephrine but rather
      inhibited its uptake. As with forskolin and cholera toxin, physiological
      signaling molecules such as vasoactive intestinal polypeptide (VIP) and AMP, for
      which PC12 cells are known to have receptors linked to activation of adenylate
      cyclase, also inhibited norepinephrine uptake. The inhibitory effects of
      dibutyryl cAMP, VIP, and AMP were dose dependent, and EC50 values were estimated
      to be 100 microM, 10 nM, and 1.0 microM, respectively. The inhibition profile of
      dibutyryl cAMP over the time course of norepinephrine uptake was biphasic:
      inhibition became clearly detectable after the cytosolic pool of norepinephrine
      had been saturated. This profile is similar to that of reserpine. Nomifensine,
      however, inhibited uptake at a rather constant rate throughout the entire time
      course. The ATP-dependent serotonin uptake by digitonin-permeabilized cells was
      lowered to approximately 50% that of the control by dibutyryl cAMP treatment
      before permeabilization, indicating inhibition of vesicular monoamine transport.
      This effect was also dependent on a dibutyryl cAMP concentration with an EC50 of
      < or = 100 microM.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7830054
TI  - Expression of the proenkephalin A gene and [Met5]-enkephalin secretion induced by
      arachidonic acid in bovine adrenal medullary chromaffin cells: involvement of
      second messengers.
AB  - We have previously reported that arachidonic acid (AA) increases the long-term
      secretion of [Met5]-enkephalin (ME) and the expression of proenkephalin A
      (proENK) mRNA in bovine adrenal medullary chromaffin (BAMC) cells. To
      characterize the underlying signal transductional mechanisms for the AA-induced
      responses, the interactions of AA with several second messenger systems were
      studied. Long-term (24-h) treatment with AA (100 microM) increased both the
      secretion of ME and the expression of proENK mRNA. Pretreatment of BAMC cells
      with nimodipine (1 microM), but not with omega-conotoxin GVIA (1 microM),
      inhibited the secretion of ME and the expression of proENK mRNA induced by AA.
      Calmidazolium (1 microM), a calmodulin antagonist, also significantly inhibited
      AA-induced responses. However, a protein kinase C (PKC) inhibitor, sphingosine
      (36 microM), was ineffective in blocking AA-induced responses. In addition, the
      down-regulation of PKC by phorbol 12-myristate 13-acetate (0.1 microM) for 48 h
      did not inhibit the AA-induced responses. Forskolin (5 microM), an adenyl cyclase
      activator, alone increased the secretion of ME as well as proENK mRNA levels and,
      when coincubated with AA, showed an additive effect on the secretion of ME and
      the levels of proENK mRNA. The results suggest that the Ca2+/calmodulin pathway,
      but not the protein kinase A or PKC pathway, is partially involved in mediating
      the AA-induced increases of the long-term secretion of ME and the levels of
      proENK mRNA.

PMID- 7830055
TI  - Determination of the lumped constant for the alpha-methyltryptophan method of
      estimating the rate of serotonin synthesis.
AB  - The lumped constant (LC) for the alpha-methyl-L-tryptophan method to convert the
      brain's uptake of labeled alpha-methyl-L-tryptophan into the regional rate of
      serotonin synthesis was estimated. The method involved independently estimating
      the unidirectional uptake constant of the tracer (alpha-[14C]methyl-L-tryptophan)
      to the tissue and the tracee (tryptophan) (with the addition of a radioactive
      compound) and calculating their ratio. The LC was estimated from logarithmically
      transformed data. Similar experiments were performed using rats treated with the
      drug probenecid, which blocks the efflux of 5-hydroxyindoleacetic acid (a
      metabolite of serotonin) from the brain. The experiments using probenecid,
      corrected for the difference in the levels of plasma free tryptophan (increased
      in probenecid-treated rats) relative to control experiments, gave an average LC
      for the rat brain of 0.46 +/- 0.14 (mean +/- SD). This value was not
      significantly different from the one obtained in controls (0.43 +/- 0.13). In
      addition, the LC was also calculated using unidirectional uptake constants in the
      probenecid-treated rats for alpha-methyl-L-tryptophan and L-tryptophan. This LC
      value was 0.39 +/- 0.10. There was no significant difference between these three
      LC values. Thus, an average +/- SD LC of 0.42 +/- 0.07 for 28 brain structures
      investigated in this study was obtained. Statistically the LC obtained in
      different structures had a variability that could be accounted for by errors in
      measurements alone. In other words, dispersion in the LC values could be fully
      accounted for by chance alone. Data confirmed that the LC value did not change
      when the rate of serotonin synthesis was increased by probenecid treatment. We
      also showed that the rate of 5-hydroxyindoleacetic acid accumulation in
      probenecid-treated rats was 58 pmol g-1 min-1 (rat brain), which is about twice
      as much as reported by others for a normal rat. This difference could also be
      accounted for by the increase in the plasma level of free tryptophan in
      probenecid-treated rats.

PMID- 7830056
TI  - Inhibition by lamotrigine of the generation of nitric oxide in rat forebrain
      slices.
AB  - Depolarization of adult rat forebrain slices with veratrine induced the release
      of excitatory amino acids (glutamate and aspartate), the synthesis of nitric
      oxide (NO), and increases in cyclic GMP (cGMP). The NO synthase inhibitors N
      omega-monomethyl-L-arginine and N omega-nitro-L-arginine methyl ester decreased
      the release of NO and the levels of cGMP without affecting the release of
      excitatory amino acids. In contrast, the antiepileptic drug lamotrigine inhibited
      the release of excitatory amino acids and of NO, and decreased the levels of cGMP
      without causing a significant direct inhibition of the NO synthase. Furthermore,
      the synthesis of NO and the increases in cGMP induced by veratrine were partially
      blocked by the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 but not by
      6-nitro-7-sulphamobenzo (f) quinoxaline-2,3-dione, a non-NMDA receptor
      antagonist. Neither of these compounds inhibited directly the NO synthase or the
      release of excitatory amino acids. Thus, these three types of compound act as an
      inhibitor of voltage-sensitive sodium channels (lamotrigine), as a receptor
      antagonist (MK-801), or as direct inhibitors of the NO synthase, to block the
      pathway leading to increased cGMP after veratrine depolarization. It is likely
      that some of the pharmacological and therapeutic actions shared by these three
      types of compound are, at least in part, a consequence of inhibition of the
      synthesis of NO.

PMID- 7830057
TI  - Coupling of the human Y2 receptor for neuropeptide Y and peptide YY to guanine
      nucleotide inhibitory proteins in permeabilized SMS-KAN cells.
AB  - Using guanine nucleotides, pertussis toxin, and specific antisera against the
      COOH-terminals of the alpha-subunits of Gi1/2, Gi3, and G(o), the binding and
      biological response of the Y2 receptor (Y2R) for peptide YY (PYY) was probed in
      SMS-KAN neuroblastoma cells. The specific binding of radiolabeled PYY exhibited a
      single apparent dissociation constant, KD = 76 pM for intact cells and KD = 906
      pM for permeabilized cells. However, other data suggested existence of multiple
      receptor affinity states. A shift in KD and a decrease in apparent number of
      binding sites (Bmax) was observed in permeabilized cells when incubated with
      guanine nucleotides. By contrast, in membrane preparations guanine nucleotides
      induced only a decrease in Bmax. In intact cells, agonist exposure inhibited the
      intracellular accumulation of forskolin-stimulated cyclic AMP by 80% (IC50 = 420
      nM) compared with 94% inhibition (IC50 = 380 nM) in permeabilized cells. In
      permeabilized cells, preincubation with antisera against alpha i1/2 and alpha i3
      blocked the functional response of PYY, with anti-alpha i3 being the most potent;
      whereas anti-alpha o failed to affect the cyclic AMP levels. These results
      suggest that permeabilized SMS-KAN cells serve as a good model system for
      analysis of Y2R binding kinetics and functional response and that the Y2R
      interacts directly with several different GiS (but not G(o)).

PMID- 7830058
TI  - NMDA receptors in rat cerebellum and forebrain: subtle differences in
      pharmacology and modulation.
AB  - Binding of [3H]glutamate, [3H]glycine, and the glutamate antagonist [3H]CGS-19755
      to NMDA-type glutamate receptors was examined in homogenates of rat forebrain and
      cerebellum. Most glutamate agonists had a higher affinity at the [3H]glutamate
      binding site of cerebellar NMDA receptors as compared with forebrain, whereas all
      the glutamate antagonists examined showed the reverse relationship. The
      [3H]glycine binding site of forebrain and cerebellar NMDA receptors showed a
      similar pharmacology in both brain regions. In the cerebellum, however,
      [3H]glycine bound to a second site with a 10-fold lower affinity and with a
      pharmacology that resembled that of the glycine/strychnine chloride channel. [3H]
      Glutamate binding was not affected by glycine agonists or antagonists, nor was
      [3H]glycine binding affected by glutamate agonists in either forebrain or
      cerebellum. Both CGS-19755 and 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic
      acid, glutamate antagonists, reduced [3H]-glycine binding in cerebellum, whereas
      only CGS-19755 was effective in forebrain. Glycine agonists and antagonists
      modulated [3H]CGS-19755 binding in forebrain and cerebellum to different extents
      in the two brain regions. From these studies we conclude that the cerebellar NMDA
      receptor has a different pattern of modulation at glutamate and glycine sites and
      that glycine may play a more important role in the control of NMDA function in
      the cerebellum as compared with forebrain.

PMID- 7830059
TI  - Dopamine receptor blockade inhibits the amphetamine-induced release of
      diadenosine polyphosphates, diadenosine tetraphosphate and diadenosine
      pentaphosphate, from neostriatum of the conscious rat.
AB  - The diadenosine polyphosphates diadenosine tetraphosphate (Ap4A) and diadenosine
      pentaphosphate (Ap5A) are costored with ATP and released in a calcium-dependent
      manner from neural preparations in vitro. By means of a push-pull perfusion
      system, samples from conscious rat were collected from the caudate putamen area,
      and nucleotide compounds were analyzed by HPLC. The adenine dinucleotides were
      not detectable before systemic amphetamine injection. The maximal levels were
      reached 20 min after injection, independently of the dose. The EC50 values for
      amphetamine-induced release of dinucleotides were 2.04 +/- 0.15 and 2.43 +/- 0.36
      mg/kg for Ap4A and Ap5A, respectively. Amphetamine doses higher than 5 mg/kg did
      not increase the dinucleotide release, the maximal values being 12.9 +/- 0.9 and
      11.5 +/- 0.9 pmol/fraction for Ap4A and Ap5A, respectively, which corresponds
      with 64.5 and 57.5 nM in the samples. Adenosine and AMP were present in push-pull
      samples from rat brain under basal conditions. Their levels were 15 pmol/fraction
      (75 nM) and 50 pmol/fraction (250 nM) for adenosine and AMP, respectively. A
      significant increase was obtained for both compounds after amphetamine injection.
      The adenosine increase reached 45 pmol/sample (225 nM), which was 200% of the
      basal value 20 min after the stimulant administration. The increase at other
      times was not significant. The AMP levels increased significantly from 10 to 50
      min. The maximal level was reached 20 min after amphetamine injection, with 150
      pmol/fraction (750 nM), which represents a 200% increase with respect to the
      basal level. The adenine dinucleotide release was blocked by the dopamine
      receptor antagonist haloperidol, which returned the levels to the control basal
      values.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7830060
TI  - Characterization of ligand binding to the cannabinoid receptor of rat brain
      membranes using a novel method: application to anandamide.
AB  - Ligand binding to the cannabinoid receptor of brain membranes has been
      characterized using [3H]CP 55,940 and the Multiscreen Filtration System. Binding
      of [3H]CP 55,940 is saturable and reaches equilibrium by 45 min at room
      temperature. At a concentration of 10 micrograms of membrane protein/well, the KD
      for [3H]CP 55,940 is 461 pM and the Bmax is 860 fmol/mg of protein. The apparent
      KD of [3H]CP 55,940 is dependent upon tissue protein concentration, increasing to
      2,450 pM at 100 micrograms of membrane protein. Binding of [3H]CP 55,940 is
      dependent upon the concentration of bovine serum albumin in the buffer; the
      highest ratio of specific to nonspecific binding occurs between 0.5 and 1.0
      mg/ml. The Ki of anandamide, a putative endogenous ligand of the cannabinoid
      receptor, is 1.3 microM in buffer alone and 143 nM in the presence of 0.15 mM
      phenylmethylsulfonyl fluoride. When [14C]anandamide is incubated with rat
      forebrain membranes at room temperature, it is degraded to arachidonic acid; the
      hydrolysis is inhibited by 0.15 mM phenylmethylsulfonyl fluoride. These results
      support the hypothesis that anandamide is a high-affinity ligand of the
      cannabinoid receptor and that it is rapidly degraded by membrane fractions.

PMID- 7830061
TI  - Differential effects of 4'-chlorodiazepam on expressed human GABAA receptors.
AB  - The interactions of the atypical benzodiazepine 4'-chlorodiazepam (Ro 5-4864)
      with functionally expressed human GABAA receptor cDNAs were determined.
      Cotransfection of human alpha 2, beta 1, and gamma 2 subunits was capable of
      reconstituting a 4'-chlorodiazepam recognition site as revealed by a dose
      dependent potentiation of t-[35S]butylbicyclophosphorothionate ([35S]-TBPS)
      binding to the GABA-activated chloride channel. This site is found on GABAA
      receptor complexes containing sites for GABA agonist-like benzodiazepines and
      neuroactive steroids. The importance of the alpha subunit was further
      demonstrated as substitution of either alpha 1 or alpha 3 for the alpha 2 subunit
      did not reconstitute a 4'-chlorodiazepam recognition site that was capable of
      modulating [35S]TBPS binding under the same experimental conditions. The 4'
      chlorodiazepam modulatory site was shown to be distinct from the benzodiazepine
      site, but the phenylquinolines PK 8165 and PK 9084 produced effects similar to 4'
      chlorodiazepam, consistent with the previous analysis of the 4'-chlorodiazepam
      site in brain homogenates. Further analysis of the subunit requirements revealed
      that coexpression of alpha 2 and beta 1 alone reconstituted a 4'-chlorodiazepam
      recognition site. It is interesting, however, that the 4'-chlorodiazepam site was
      found to inhibit [35S]TBPS binding to the GABA-activated chloride channel. Thus,
      the 4'-chlorodiazepam site may be reconstituted with only the alpha and beta
      polypeptides.

PMID- 7830062
TI  - Dynamic storage of dopamine in rat brain synaptic vesicles in vitro.
AB  - The dynamics of catecholamine storage were studied in highly purified, small
      synaptic vesicles from rat brain both during active uptake or after inhibiting
      uptake with reserpine, tetrabenazine, or removal of external dopamine. To assess
      turnover during active uptake, synaptic vesicles were allowed to accumulate
      [3H]dopamine ([3H]DA) for approximately 10 min and then diluted 20-fold into a
      solution containing unlabeled DA under conditions such that active uptake could
      continue. After dilution, [3H]DA was lost with single exponential kinetics at a
      half-time of approximately 4 min at 30 degrees C in 8 mM Cl- medium, in which
      both voltage and H+ gradients are present in the vesicles. In 90 mM Cl- medium,
      in which high H+ and Cl- gradients but no voltage gradient are present, [3H]DA
      escaped at a half-time of approximately 7 min. In both high and low Cl- media,
      approximately 40% of [3H]DA efflux was blocked by reserpine or tetrabenazine. The
      residual efflux also followed first-order kinetics. These results indicate that
      two efflux pathways were present, one dependent on DA uptake (and thus on the
      presence of external DA) and the other independent of uptake, and that both
      pathways function regardless of the type of electrochemical H+ gradient in the
      vesicles. The presence of both uptake-dependent and -independent efflux was
      observed in experiments using DA-free medium, instead of uptake inhibitors, to
      prevent uptake. Uptake-independent efflux showed molecular selectivity for
      catecholamines; [14C]DA was lost about three times faster than [3H]norepinephrine
      after adding tetrabenazine directly (without dilution) to vesicles that had taken
      up comparable amounts of each amine. In addition, the first-order rate constant
      for uptake-independent efflux showed little change over a 60-fold range of
      internal DA concentrations, which suggests that this pathway had a high transport
      capacity. All efflux was blocked at 0 degrees C, suggesting that efflux did not
      occur through a large pore. There was little or no change in the proton gradient
      in synaptic vesicles, monitored by [14C]methylamine equilibration, during the
      experimental manipulations used here. Thus, the driving force for catecholamine
      uptake remained approximately constant. The physiological role of uptake
      independent efflux could be to allow the monoamine content of synaptic vesicles
      to be regulated over a time range of minutes and, thereby, control the amount
      released by exocytosis. These results imply that catecholamines turn over with a
      half-time of minutes during active uptake by brain synaptic vesicles in vitro.

PMID- 7830063
TI  - Identification of D3 and sigma receptors in the rat striatum and nucleus
      accumbens using (+/-)-7-hydroxy-N,N-di-n-[3H]propyl-2-aminotetralin and
      carbetapentane.
AB  - Cross-reactions between dopamine D3 and sigma receptor ligands were investigated
      using (+/-)-7-hydroxy-N,N-di-n-[3H]propyl-2-aminotetralin [(+/-)-7-OH-[3H]-DPAT],
      a putative D3-selective radioligand, in conjunction with the unlabeled sigma
      ligands 1,3-di(2-tolyl)guanidine (DTG), carbetapentane, and R(-)-N-(3-phenyl-1
      propyl)-1-phenyl-2-aminopropane [R(-)-PPAP]. In transfected CCL1.3 mouse
      fibroblasts expressing the human D3 receptor, neither DTG nor carbetapentane (0.1
      microM) displaced (+/-)-7-OH-[3H]DPAT binding. R(-)-PPAP (0.1 microM) displaced
      39.6 +/- 1.0% of total (+/-)-7-OH-[3H]DPAT binding. In striatal and nucleus
      accumbens homogenates, (+/-)-7-OH-[3H]DPAT labeled a single site (15-20 fmol/mg
      of protein) with high (1 nM) affinity. Competition analysis with carbetapentane
      defined both high- and low-affinity sites in striatal (35 and 65%, respectively)
      and nucleus accumbens (59 and 41%, respectively) tissue, yet R(-)-PPAP identified
      two sites in equal proportion. Carbetapentane and R(-)-PPAP (0.1 microM)
      displaced approximately 20-50% of total (+/-)-7-OH-[3H]DPAT binding in striatum,
      nucleus accumbens, and olfactory tubercle in autoradiographic studies, with the
      nucleus accumbens shell subregion exhibiting the greatest displacement. To
      determine directly (+)-7-OH-[3H]DPAT binding to sigma receptors, saturation
      analysis was performed in the cerebellum while masking D3 receptors with 1 microM
      dopamine. Under these conditions (+)-7-OH-[3H]DPAT labeled sigma receptors with
      an affinity of 24 nM. These results suggest that (a) (+/-)-7-OH-[3H]DPAT binds D3
      receptors with high affinity in rat brain and (b) a significant proportion of (+/
      )-7-OH-[3H]DPAT binding consists of sigma 1 sites and the percentages of these
      sites differ among the subregions of the striatum and nucleus accumbens.

PMID- 7830064
TI  - Stimulation of cyclic GMP accumulation by sodium nitroprusside is potentiated via
      a Gs mechanism in intact pinealocytes.
AB  - Cyclic GMP accumulation in pinealocytes is elevated > 100-fold by norepinephrine
      (NE) through a mechanism involving conjoint activation of alpha 1- and beta 1
      adrenergic receptors. Little or no stimulation occurs if either alpha 1- or beta
      1-adrenergic receptors alone are activated. It appears that alpha 1-adrenergic
      effects are mediated by Ca2+ acting in part through nitric oxide (NO), and beta 1
      adrenergic effects are mediated by Gs. In the study presented here we
      investigated effects of adrenergic agonists or related postreceptor-active agents
      on stimulation of pineal cyclic GMP accumulation by the NO generator sodium
      nitroprusside (NP). The cyclic GMP response to NP (1 mM) was potentiated by NE
      and isoproterenol (ISO) but not by phenylephrine, indicating that activation of
      beta 1-adrenergic receptors potentiates the effects of NP. Similarly, vasoactive
      intestinal peptide (VIP), cholera toxin (CTX), and forskolin, all of which are
      known to mimic the effects of ISO in this system, also potentiated the effects of
      NP. In contrast, neither dibutyryl cyclic AMP nor agents that elevate
      intracellular Ca2+ levels caused marked potentiation of the effects of NP on
      pineal cyclic GMP. Depletion (90%) of Gs alpha by 21-h treatment with CTX reduced
      beta-adrenergic potentiation of NP. These findings indicate that beta-adrenergic
      agonists and VIP potentiate the effects of NP through a mechanism involving Gs.
      The molecular basis of this action may be an increase in guanylyl cyclase
      responsiveness to NO.

PMID- 7830065
TI  - Dopamine neurotoxicity: inhibition of mitochondrial respiration.
AB  - Dopamine, due to metabolism by monoamine oxidase or autoxidation, can generate
      toxic products such as hydrogen peroxide, oxygen-derived radicals, semiquinones,
      and quinones and thus exert its neurotoxic effects. Intracerebroventricular
      injection of dopamine into rats pretreated with the monoamine oxidase
      nonselective inhibitor pargyline caused mortality in a dose-dependent manner with
      LD50 = 90 micrograms. Norepinephrine was less effective with LD50 = 141
      micrograms. The iron chelator desferrioxamine completely protected against
      dopamine-induced mortality. In the absence of pargyline more rats survived,
      indicating that the products of dopamine enzymatic metabolism are not the main
      contributors to dopamine-induced toxicity. Biochemical analysis of frontal cortex
      and striatum from rats that received a lethal dose of dopamine did not show any
      difference from control rats in lipid and protein peroxidation and glutathione
      reductase and peroxidase activities. Moreover, dopamine significantly reduced the
      formation of iron-induced malondialdehyde in vitro, thus suggesting that earlier
      events in cell damage are involved in dopamine toxicity. Indeed, dopamine
      inhibited mitochondrial NADH dehydrogenase activity with IC50 = 8 microM, and
      that of norepinephrine was twice as much (IC50 = 15 microM). Dopamine-induced
      inhibition of NADH dehydrogenase activity was only partially reversed by
      desferrioxamine, which had no effect on norepinephrine-induced inhibition. These
      results suggest that catecholamines can cause toxicity not only by inducing an
      oxidative stress state but also possibly through direct interaction with the
      mitochondrial electron transport system. The latter was further supported by the
      ability of ADP to reverse dopamine-induced inhibition of NADH dehydrogenase
      activity in a dose-dependent manner.

PMID- 7830066
TI  - Chronic treatment of C6 glioma cells with antidepressant drugs increases
      functional coupling between a G protein (Gs) and adenylyl cyclase.
AB  - It has been reported that antidepressant treatment in rats results in a
      significant increase of Gs-mediated stimulation of adenylyl cyclase and this
      effect correlates well with the clinical therapeutic response. This increased
      activity occurs despite a down-regulation of several receptors linked normally to
      the stimulation of that enzyme. To distinguish between these effects and to
      determine whether presynaptic components of the cell are required, C6 glioma
      cells were treated with antidepressants. Tricyclic (amitriptyline and
      desipramine) or atypical (iprindole) antidepressant exposure to C6 cells for 5
      days significantly increased guanylyl-5'-imidodiphosphate [Gpp(NH)p]-stimulated
      adenylyl cyclase activity in membrane preparations in a manner similar to that
      seen for rat brain membranes after 21-day treatment. This effect was drug dose
      and exposure time dependent. Nevertheless, stimulation of adenylyl cyclase by
      isoproterenol was decreased after antidepressant treatment. By comparison, the
      antidepressant-induced beta-receptor desensitization occurred earlier than the
      enhancement of Gpp(NH)p-activated adenylyl cyclase, and extensive desensitization
      of beta receptors by isoproterenol treatment did not enhance the Gpp(NH)p
      stimulated adenylyl cyclase activity. These results indicated that the
      antidepressant has a direct effect on cell signaling and this enhanced Gpp(NH)p
      stimulated adenylyl cyclase activity is not correlated with desensitization of
      beta-adrenergic receptor stimulated adenylyl cyclase. These data contribute to
      the suggestion that G proteins (especially Gs) are the target of antidepressant
      actions. Immunoblotting showed that neither the number of G protein subunits
      (alpha s, alpha i, alpha o, and beta) nor their association with the plasma
      membrane was changed after antidepressant treatment.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7830067
TI  - Specific delay of degradation of mitochondrial ATP synthase subunit c in late
      infantile neuronal ceroid lipofuscinosis (Batten disease).
AB  - Subunit c is normally present as an inner mitochondrial membrane component of the
      F0 section of the ATP synthase complex, but in the late infantile form of
      neuronal ceroid lipofuscinosis (NCL) it was also found in lysosomes in high
      concentrations. To explore the mechanism of storage of subunit c, the rates of
      degradation and synthesis of subunit c were measured in fibroblast cell types
      from controls and patients with the late infantile form of NCL. The radiolabel
      from subunit c decreased with time in control cells, whereas no apparent loss of
      radioactivity of subunit c was found in patients' cells. There were no
      significant differences between control cells and cells with disease in the
      degradation of cytochrome oxidase subunit IV, an inner membrane protein of
      mitochondria. A combination of pulse-chase and subcellular fractionation analysis
      showed that a delay of intramitochondrial loss from prelabeled subunit c was seen
      in all diseased cells tested. Lysosomal appearance of labeled subunit c could be
      detected after chase for more than 1 week and its radioactivities were variable
      among diseased cell types. The biosynthetic rate of subunit c was almost the same
      in both control and patient cells. Northern blotting analyses showed that mRNAs
      for P1 and P2 genes had no significant difference in lengths and amounts between
      control and patient cells. Results suggest a specific failure in the degradation
      of subunit c after its normal inclusion in mitochondria and its consequent
      accumulation in lysosomes. This is the first direct evidence to show a delay of
      subunit c degradation in the cells from the late infantile form of NCL.

PMID- 7830068
TI  - High resolution proton NMR spectroscopy of multiple sclerosis lesions.
AB  - Tissue from postmortem multiple sclerosis and normal control brains was extracted
      with perchloric acid and analysed using proton NMR spectroscopy. The content of N
      acetyl-derived groups (the sum of N-acetyl-aspartate, acetate, and N
      acetylaspartylglutamate) was decreased in multiple sclerosis plaques compared
      with normal control white matter (mean, 4.36 vs. 6.64 mumol/g wet weight). In
      normal appearing white matter adjacent to plaques a corresponding decrease was
      seen, with no change in white matter distant from plaques. A decrease in the
      content of total creatine was observed in multiple sclerosis plaques in
      comparison with normal control white matter (mean, 4.64 vs. 6.56 mumol/g wet
      weight), which correlated strongly with the decrease in N-acetyl-derived groups.
      No changes in other metabolites such as total choline or myo-inositol were seen.
      The decreases in content of N-acetyl-derived groups are in agreement with
      observations from in vivo proton NMR spectroscopy in multiple sclerosis patients.
      The decrease in total creatine is in contrast to most of the observations made in
      vivo where total creatine is assumed to be unchanged and metabolite levels are
      often expressed as a total creatine ratio. The use of a total creatine ratio in
      vivo could lead to an underestimation of reductions in N-acetylaspartate and an
      apparent increase in other metabolites in the multiple sclerosis lesion.

PMID- 7830069
TI  - Neurochemical correlates of dementia severity in Alzheimer's disease: relative
      importance of the cholinergic deficits.
AB  - Cholinergic markers, neuropeptides, and amines and their metabolites were sampled
      from identical specimens across 10 neocortical regions in a large sample of
      Alzheimer's disease (AD) cases and controls. Levels of choline acetyltransferase,
      acetylcholinesterase, somatostatin, corticotropin-releasing factor, serotonin,
      and 5-hydroxyindoleacetic acid were significantly reduced in AD versus controls.
      After data reduction, the most descriptive neurochemical indices were used to
      examine the relationship of neurochemical measures and dementia severity within
      the AD sample, controlling for age effects. Dementia severity ratings were based
      on antemortem assessments (46.9% of AD sample) and postmortem chart review (53.1%
      of the AD sample). Choline acetyltransferase activity was highly correlated with
      clinical dementia ratings across the neocortex of the AD cases. Somatostatin and
      corticotropin-releasing factor levels were correlated with dementia severity only
      when control cases were included in the analyses. None of the amines, their
      metabolites, or the neuropeptides quantified related significantly to dementia
      severity in the AD cohort. These data (a) confirm the strong association of
      cholinergic deficits with functional impairment in AD and show that this
      association is independent of age and (b) suggest that of all the neurochemical
      species quantified, the cholinergic indices may be unique in their association
      with dementia severity.

PMID- 7830070
TI  - Increased inositol 1,4,5-trisphosphate accumulation correlates with an up
      regulation of bradykinin receptors in Alzheimer's disease.
AB  - An alteration in signal transduction systems in Alzheimer's disease (AD) would
      likely be of pathophysiological significance, because these processes control
      normal brain functions. Previously, a diminished beta-adrenergic-mediated cyclic
      AMP response was found in cultured fibroblasts from AD patients. Because cross
      talk between the phosphoinositide and cyclic AMP pathways exists, the
      phosphoinositide cascade was studied under conditions that were similar to those
      for studying the cyclic AMP response. Cells from AD patients and age-matched
      controls responded to bradykinin (BK) and released inositol 1,4,5-trisphosphate
      [Ins(1,4,5)P3] in a time- and dose-dependent manner. The level of Ins(1,4,5)P3
      increased rapidly and transiently in response to BK, peaked at 5 s, but still
      remained 116-132% above the basal level by 30 s. Although the temporal patterns
      were similar in both groups, the Ins(1,4,5)P3 concentrations in AD fibroblasts
      were 73 and 89% above levels in the age-matched controls at 5 and 10 s,
      respectively. Prostaglandin E1 also increased Ins(1,4,5)P3 formation, but this
      response was not different between the two groups. Although KD (affinity) values
      for the BK receptor were similar in both control and AD cells, the number of BK
      receptors (Bmax) was significantly elevated in AD fibroblasts (186.8 +/- 0.8
      fmol/mg of protein) as compared with control fibroblasts (57.2 +/- 15.3 fmol/mg
      of protein). These results indicate that the elevated Ins(1,4,5)P3 production in
      response to BK in AD fibroblasts is positively correlated with an increase in the
      receptor numbers.

PMID- 7830071
TI  - Guanosine triphosphate binding to beta-subunit of tubulin in Alzheimer's disease
      brain: role of microtubule-associated protein tau.
AB  - In Alzheimer's disease, paired helical filaments composed mainly of abnormally
      phosphorylated tau accumulate in certain selected neurons of the brain, and
      microtubules are rarely seen in the affected cells. In the present study, the
      binding of 32P-labeled 8-azidoguanosine triphosphate ([gamma-32P]8N3GTP), the
      photoaffinity analogue of GTP to the beta-subunit of tubulin in brain homogenates
      was found to be markedly lower in patients with Alzheimer's disease than in aged
      control human cases. No significant differences were observed in the levels of
      the alpha- and beta-subunits of tubulin between Alzheimer's disease and control
      brains obtained 2-7 h postmortem. In nine of 19 Alzheimer's disease and 11 of 12
      control autopsied brains (2-7 h postmortem and stored at -75 degrees C) tubulin
      was isolated successfully from brain cytosol by in vitro polymerization induced
      with DEAE-dextran. The GTP binding was observed in the two cycled assembled
      microtubule preparations from all the normal control, and in eight of nine
      Alzheimer's disease cases. Alzheimer's disease microtubule preparations contained
      varying amounts of abnormally phosphorylated tau, whereas no abnormal tau was
      detected in the control brain preparations. Addition of bovine tau to bovine,
      normal human, and Alzheimer's disease brain tubulin preparations markedly
      increased GTP binding to the beta-subunit. An alkaline phosphatase-treated paired
      helical filament-enriched preparation increased by approximately twofold the GTP
      binding to bovine brain tubulin. GTP binding to tubulin prepared by
      phosphocellulose chromatography of two cycled microtubules from three Alzheimer's
      disease and three normal control brains, revealed insignificant differences
      between the two groups. These findings have suggested that (1) tau protein
      promotes the GTP binding to the beta-subunit of tubulin, and (2) the breakdown of
      the microtubule system in brains of patients with Alzheimer's disease might in
      part be due to the abnormal phosphorylation of tau which depresses the GTP
      binding.

PMID- 7830072
TI  - Release of glutamate from striatum of freely moving rats by pros
      methylimidazoleacetic acid.
AB  - The effect of pros-methylimidazoleacetic acid (p-MIAA) was measured on the
      release of glutamate and aspartate from cerebral cortex, hippocampus, and
      striatum of freely moving rats, and on the uptake of 14C by striatal slices
      incubated in the presence of L-[14C]-glutamate. Twenty-four hours after
      implantation of a dialysis fiber, striatum, hippocampus, or cerebral cortex
      spontaneously released both glutamate and aspartate in the micromolar range. p
      MIAA (1 microM to 1 mM), added to the dialysis perfusate, elicited a
      concentration-dependent increase of glutamate release from striatum with a
      maximal increase of about threefold. This effect did not occur in hippocampus or
      cortex. In none of these regions did p-MIAA increase aspartate release
      significantly. The p-MIAA effect was not mimicked by its isomer tele-methyl
      imidazoleacetic acid. p-MIAA did not influence the uptake of glutamate by
      striatal slices. The glutamate-releasing action of p-MIAA may affect striatal
      function and explain the positive correlation between levels of p-MIAA in CSF and
      the severity of Parkinson's disease.

PMID- 7830073
TI  - Neurotoxic effect of intranigral injection of 1-methyl-4-phenylpyridinium on GABA
      containing neurons and its relation to circling behavior.
AB  - The ionic species 1-methyl-4-phenylpyridinium (MPP+) seems to be the metabolite
      responsible for the damage to dopaminergic neurons occurring after administration
      of the parkinsonian drug 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. In the
      present study we show that the unilateral stereotaxic microinjection of MPP+ into
      the substantia nigra pars reticulata in rats produces immediately intense and
      long-lasting (up to 96 h) contralateral turning behavior in a dose-dependent
      manner. This behavioral effect was correlated with a dose- and time-dependent
      decrease (up to 90%) of glutamate decarboxylase activity and with a notable loss
      of neurons in the injected nigra reticulata. GABA levels in the injected nigra
      were also decreased, whereas the dopamine concentration in the ipsilateral
      striatum was not affected at 24 h, when maximal behavioral effects were observed.
      The circling behavior was prevented by the dopamine carrier blocker nomifensine
      only during the first 2 h, whereas the dopamine receptor antagonist haloperidol
      was ineffective. The results indicate that MPP+ is toxic for inhibitory GABAergic
      neurons in the nigra pars reticulata and, furthermore, suggest that disruption of
      the function of these GABAergic neurons may be involved in the abnormal motor
      behavior produced by the injection of MPP+ in the substantia nigra.

PMID- 7830074
TI  - The sodium channel blocker and glutamate release inhibitor BW1003C87 and
      magnesium attenuate regional cerebral edema following experimental brain injury
      in the rat.
AB  - Excitatory amino acid (EAA) neurotransmitters may play a role in the
      pathophysiology of traumatic injury to the CNS. Although NMDA receptor
      antagonists have been reported to have therapeutic efficacy in animal models of
      brain injury, these compounds may have unacceptable toxicity for clinical use.
      One alternative approach is to inhibit the release of EAAs following traumatic
      injury. The present study examined the effects of administration of a novel
      sodium channel blocker and EAA release inhibitor, BW1003C87, or the NMDA receptor
      associated ion channel blocker magnesium chloride on cerebral edema formation
      following experimental brain injury in the rat. Animals (n = 33) were subjected
      to fluid percussion brain injury of moderate severity (2.3 atm) over the left
      parietal cortex. Fifteen minutes after injury, the animals received a constant
      infusion of BW1003C87 (10 mg/kg, i.v.), magnesium chloride (300 mumol/kg, i.v.),
      or saline over 15 min (2.75 ml/kg/15 min). In all animals, regional tissue water
      content in brain was assessed at 48 h after injury, using the wet weight/dry
      weight technique. In saline-treated control animals, fluid percussion brain
      injury produced significant regional brain edema in injured left parietal cortex
      (p < 0.001), the cortical area adjacent to the site of maximal injury (p <
      0.001), left hippocampus (p < 0.001), and left thalamus (p = 0.02) at 48 h after
      brain injury. Administration of BW1003C87 15 min postinjury significantly reduced
      focal brain edema in the cortical area adjacent to the site of maximal injury (p
      < 0.02) and left hippocampus (p < 0.01), whereas magnesium chloride attenuated
      edema in left hippocampus (p = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7830075
TI  - Differential correlation between translocation and down-regulation of
      conventional and new protein kinase C isozymes in C6 glioma cells.
AB  - Correlation between translocation and down-regulation of conventional protein
      kinase C alpha (cPKC alpha) and new PKC delta (nPKC delta) induced by 12-O
      tetradecanoylphorbol 13-acetate (TPA) at different time courses (5 min, 30 min, 1
      h, 3 h, 6 h, 10 h, 17 h, and 24 h) was studied in C6 glioma cells. From the dose
      dependent translocations of these two isoforms by 10-min treatment with TPA (1,
      3, 10, 30, 100, 300, and 1,000 nM), we found that cPKC alpha was translocated by
      3-1,000 nM and nPKC delta was translocated by 10-1,000 nM TPA. Both isoforms were
      maximally translocated by 100-1,000 nM TPA, whereas 1 nM did not translocate
      these two isoforms. When the cells were treated with 1,000 nM TPA for 5 min to 17
      h, the translocation of these two isoforms occurred rapidly after 5-min treatment
      and could be sustained for 1 h, whereas down-regulation occurred after 3-h
      treatment and almost complete down-regulation was observed after 17-h treatment.
      However, the extent of down-regulation of nPKC delta was greater than that of
      cPKC alpha at 3-, 6-, and 10-h treatment. Further studies by using different
      doses of TPA (100, 10, 3, and 1 nM) and extending the time to 24 h showed that
      cPKC alpha was more resistant to down-regulation. This conventional isoform was
      maintained at a translocation state even after long-term treatment with 3-100 nM
      TPA, and complete down-regulation was only shown after 1,000 nM
      treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7830076
TI  - L-dopa cytotoxicity to PC12 cells in culture is via its autoxidation.
AB  - The mechanism of cytotoxicity of L-DOPA was studied in the rat pheochromocytoma
      PC12 cell line. The cytotoxicity of L-DOPA to PC12 cells was time and
      concentration dependent. Carbidopa, which inhibited the conversion of L-DOPA to
      dopamine, did not protect against L-DOPA cytotoxicity in PC12 cells. Furthermore,
      clorgyline, a selective inhibitor of monoamine oxidase type A, and pargyline, an
      inhibitor of both monoamine oxidase types A and B, both did not have an effect on
      L-DOPA toxicity. These findings suggest that cytotoxicity was not due to dopamine
      formed from L-DOPA. Catalase or superoxide dismutase each partially protected
      against L-DOPA toxicity in PC12 cells. In combination, the effects were
      synergistic and provided almost total protection against cytotoxicity. 6-Cyano-7
      nitroquinoxaline-2,3-dione, an antagonist of non-NMDA receptors, did not protect
      against L-DOPA toxicity. These data suggest that toxicity of L-DOPA is most
      likely due to the action of free radicals formed as a result of its autoxidation.
      Furthermore, these findings suggest that patients on long-term L-DOPA therapy are
      potentially at risk from the toxic intermediates formed as a result of its
      autoxidation.

PMID- 7830077
TI  - Effluxes of 3,4-dihydroxyphenylalanine, 3,4-dihydroxyphenylglycol, and
      norepinephrine from four blood vessels during basal conditions and during nerve
      stimulation.
AB  - Effluxes of 3,4-dihydroxyphenylalanine, 3,4-dihydroxyphenyglycol, and
      norepinephrine from four superfused canine blood vessels (saphenous and portal
      veins and mesenteric and pulmonary arteries) were studied under basal conditions
      and during nerve stimulation. From quantification of the compounds a series of
      indices of activities at neuroeffector junctions are proposed. These are (a)
      basal overflow of 3,4-dihydroxyphenylglycol as an index of vesicular-cytoplasmic
      translocation of norepinephrine, (b) the increase in 3,4-dihydroxyphenyglycol
      overflow attributable to nerve stimulation as an index of neuronal reuptake of
      norepinephrine released by stimulation, (c) the sum of the increases in overflows
      of norepinephrine and 3,4-dihydroxyphenylglycol attributable to nerve stimulation
      as an index of evoked release of norepinephrine, and (d) the efflux of 3,4
      dihydroxyphenylalanine as an index of the activity of tyrosine hydroxylase, the
      rate-limiting enzyme in the synthesis of norepinephrine. There were clear
      differences between these indices in the vessels. Correlation coefficients of the
      indices among vessels indicated that a high tissue norepinephrine level was
      associated with high biosynthetic capacity and high vesicular-cytoplasmic
      exchange but not with high release. There was no evidence suggesting feedback
      inhibition of synthesis by neuroplasmic norepinephrine--whether arising from
      vesicular-cytoplasmic translocation or from reuptake from the junctional cleft.
      The major value of these indices will probably be in determining the integrated
      effects of pharmacologic agents at neuroeffector junctions in different blood
      vessels.

PMID- 7830078
TI  - Characterization of monoclonal antibodies that inhibit the catalytic activity of
      acetylcholinesterases.
AB  - Monoclonal antibodies were generated against fetal bovine serum
      acetylcholinesterase and fetal bovine serum acetylcholinesterase inhibited by
      diisopropyl fluorophosphate or 7-(methylethoxyphosphinyloxy)-1-methylquinolinium
      iodide. Six monoclonal antibodies inhibited 70 to > 98% of the catalytic activity
      of fetal bovine serum acetylcholinesterase. Inhibition of serum
      acetylcholinesterase from several mammalia by four monoclonal antibodies showed
      broad cross-reactivity. In all cases, monoclonal antibodies bound to the native
      form of acetylcholinesterases. None reacted with serum butyrylcholinesterases
      from various species. Although all monoclonal antibodies inhibited catalytic
      activity of acetylcholinesterases, the site of interaction with
      acetylcholinesterase appeared to differ for several antibodies. Two types of
      acetylcholinesterase:monoclonal antibody complexes were formed: one between
      tetrameric forms and another between catalytic subunits within the tetramer.
      Monoclonal antibodies that inhibited acetylcholinesterase activity at > 98% also
      considerably slowed binding of diisopropyl fluorophosphate and other
      organophosphorus compounds to the acetylcholinesterase:monoclonal antibody
      complex. Binding of these monoclonal antibodies to acetylcholinesterase
      influenced function of the enzyme's peripheral anionic site. None of the
      antibodies bound to the esteratic site of acetylcholinesterase. Monoclonal
      antibodies caused changes in catalytic activity of acetylcholinesterase by
      interaction at a site remote from the catalytic site, presumably at the entrance
      to the active site gorge.

PMID- 7830079
TI  - Interleukin-6 production by Schwann cells and induction in sciatic nerve injury.
AB  - Interleukin-6 (IL-6) was produced by the spontaneously immortal Schwann cell
      clone, iSC, when cocultured with PC12 cells. The iSC cell-derived IL-6 in
      coculture conditioned media caused the neuronal differentiation of naive PC12
      cells and this bioactivity was neutralized by preincubation of conditioned media
      with antisera to IL-6. Cocultured iSC transcribe IL-6 message as confirmed by
      northern analysis. Stimuli that induce IL-6 production in the hematopoietic
      lineage induced transcription and production of IL-6 by iSC cells.
      Lipopolysaccharide, tumor necrosis factor-alpha, IL-1 alpha, IL-6, and serum
      withdrawal induced iSC cell IL-6 mRNA. The kinetics of IL-6 production was
      confirmed in the mouse IL-6-dependent B9 bioassay and that activity could be
      neutralized with antisera to IL-6. Expression of both the IL-6 receptor and the
      gp130 signal transduction component by iSC as determined by northern analysis
      suggests an autocrine regulatory mechanism. The observed iSC production of IL-6
      in vitro led to an investigation of the sciatic nerve crush model of Schwann cell
      activation in vivo. In the initial 12 h after crush injury, IL-6 message is
      induced. IL-6 mRNA expression was highest distal to the crush injury. Our in
      vitro data demonstrate that iSC cells produce IL-6 in response to PC12 cell
      coculture and to stimuli that induce IL-6 production in the hematopoietic
      lineage. The induction of IL-6 message distal to a crush injury suggests another
      mechanism by which Schwann cells facilitate peripheral nerve regeneration.

PMID- 7830080
TI  - Purification and properties of high molecular weight calpastatin from bovine
      brain.
AB  - Calcium-activated neutral proteases (calpains) are regulated by specific
      endogenous protein inhibitors, the calpastatins, which are widely distributed in
      mammalian tissues. Calpastatins from different species or in various tissues from
      the same species exhibit considerable size heterogeneity on sodium dodecyl
      sulfate (SDS) gels, reflecting both transcriptional and posttranslational
      regulation. This heterogeneity has complicated previous biochemical
      characterizations. In this study, we purified bovine brain calpastatin to
      homogeneity. The inhibitor was purified 2,463-fold from a cytosolic fraction of
      fresh bovine cerebral cortex by chromatographies on diethylaminoethyl cellulose,
      Ultrogel AcA44, phenyl-Sepharose, concanavalin A-Sepharose, and Q-Sepharose. The
      major calpastatin displayed a native molecular mass of 250-300 kDa by gel
      filtration and was composed of 125-kDa polypeptide chains by SDS-polyacrylamide
      gel electrophoresis (SDS-PAGE). Small amounts of a 68-kDa calpastatin fragment
      were detected particularly in molecules exhibiting smaller native molecular mass
      (250 kDa). When electroeluted from SDS gels, the 125- and 68-kDa polypeptides
      each inhibited calpain. The purified protein was strongly immunoreactive toward
      antibodies raised against a synthetic peptide, CEKLGEKEETIPPDYR, shown to be a
      conserved repetitive motif in the calpastatin gene or a recombinant polypeptide
      corresponding to domains L and 1 of human calpastatin. Calpastatins purified from
      bovine and human erythrocytes exhibited molecular masses of 78 and 68 kDa,
      respectively, by SDS-PAGE. Both erythrocyte calpastatins reacted strongly with
      antibodies against the conserved sequence but not with antibodies raised against
      domains L and 1 of human calpastatin, indicating that the erythrocyte inhibitors
      lack these two domains.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7830081
TI  - Aging-associated changes in the pharmacological properties of the benzodiazepine
      (omega) receptor isotypes in the rat hippocampus.
AB  - The aging-associated changes in hippocampal benzodiazepine (omega) receptor
      isotypes have been investigated in rats of the Wistar and Fischer 344 strains.
      Displacement experiments of [3H]flunitrazepam binding by zolpidem demonstrated
      that in hippocampal membranes from adult (3-month-old) Wistar strain rats, high
      (type I; omega 1)-, intermediate (type IIM; omega 2)-, and low (type IIL; omega
      5)-affinity sites for this imidazopyridine account for 27.1 +/- 7.5, 44.2 +/-
      7.5, and 28.8 +/- 5.1%, respectively. In hippocampal membranes from aged (24
      month-old) rats of the same strain, the relative abundance of these sites was
      42.8 +/- 9.3, 26.3 +/- 4, and 36.0 +/- 5.9%, respectively. In contrast, no
      significant difference was observed in the whole benzodiazepine (omega) binding
      site density between adult and aged rats. The increase in type I (omega 1)
      binding site density in the hippocampus of aged rats was also demonstrated in
      saturation experiments with [3H]zolpidem. This aging-induced increase in
      [3H]zolpidem binding was also observed in hippocampal membranes from Fischer 344
      rats. Moreover, in both rat strains, GABA induced a greater enhancement of
      [3H]zolpidem (5 nM) binding to type I (omega 1) sites (GABA shift) in aged than
      in adult hippocampal membranes. Quantitative autoradiographic analysis of
      [3H]zolpidem binding to coronal brain sections from adult and aged Fischer 344
      rats demonstrated that the aging-associated increases in the density of type I
      (omega 1) binding sites were restricted to the hippocampus. Moreover, increases
      in binding density were larger in the dentate gyrus and in the CA2 field than in
      the CA1 and CA3 fields.

PMID- 7830082
TI  - Differential effects of hypoxia on ligand binding properties of nicotinic and
      muscarinic acetylcholine receptors on cultured bovine adrenal chromaffin cells.
AB  - Hypoxia is known to disturb neuronal signal transmission at the synapse.
      Presynaptically, hypoxia is reported to suppress the release of
      neurotransmitters, but its postsynaptic effects, especially on the function of
      neurotransmitter receptors, have not yet been elucidated. To clarify the
      postsynaptic effects, we used cultured bovine adrenal chromaffin cells as a model
      of postsynaptic neurons and examined specific binding of L-[3H]nicotine (an
      agonist for nicotinic acetylcholine receptors: nAChRs) and 22Na+ flux under
      control and hypoxic conditions. Experiments were performed in media
      preequilibrated with a gas mixture of either 21% O2/79% N2 (control) or 100% N2
      (hypoxia). Scatchard analysis of the specific binding to the cells revealed that
      the KD under hypoxic conditions was twice as large as that under control
      conditions, whereas the Bmax was unchanged. When the specific [3H]nicotine
      binding was kinetically analyzed, the association constant (k1) but not the
      dissociation constant (k-1) was decreased to 40% of the control value by hypoxia.
      When the binding assay was performed using the membrane fraction, these changes
      were not observed. Nicotine-evoked 22Na+ flux into the cells was suppressed by
      hypoxia. In contrast, specific [3H]quinuclidinyl benzilate binding to the intact
      cells was unaffected by hypoxia. These results demonstrate that hypoxia
      specifically suppresses the function of nAChRs (and hence, neuronal signal
      transmission through nAChRs), primarily by acting intracellularly.

PMID- 7830083
TI  - Tumor necrosis factor-alpha regulates nicotinic responses in mixed cultures of
      sympathetic neurons and nonneuronal cells.
AB  - It is recognized that tumor necrosis factor-alpha (TNF-alpha), a pleiotropic
      cytokine, influences hormone secretion and transmitter release from central
      neurons. To examine the role of TNF-alpha as a modulator of autonomic function of
      the PNS, we measured [3H]norepinephrine ([3H]NE) secretion evoked by 1,1-dimethyl
      4-phenylpiperazinium iodide (DMPP), a nicotinic agonist, in cultures from
      neonatal rat superior cervical ganglia (SCG). We found that (1) DMPP-evoked
      [3H]NE secretion was enhanced in SCG mixed cultures treated for 48 h with
      recombinant human TNF-alpha (rhTNF-alpha) plus rat interferon-gamma (IFN-gamma)
      but not in cultures treated with either cytokine alone; (2) an increase in [3H]NE
      secretion was also observed in mixed cultures treated with recombinant murine TNF
      alpha (rmTNF-alpha) alone; and (3) the presence of nonneuronal cells or soluble
      factors released by them was required for the effect of these cytokines on
      secretion. Electrophysiologic experiments revealed an increase in nicotinic
      receptor current density in neurons from mixed cultures treated with rhTNF-alpha
      plus IFN-gamma or with rmTNF-alpha when compared with control cultures. We
      conclude that prolonged exposure to rhTNF-alpha plus IFN-gamma or rmTNF-alpha
      regulates nicotinic responses in SCG cultures via a soluble factor or factors
      secreted by nonneuronal cells.

PMID- 7830084
TI  - Cholesterol for synthesis of myelin is made locally, not imported into brain.
AB  - We examined whether cholesterol needed for myelin formation is locally
      synthesized or whether it comes from the circulation. The experimental design was
      to inject [3H]water and to use incorporation of label into brain cholesterol as a
      measure of the rate of accumulation of newly synthesized cholesterol in brain.
      The contribution of the circulation to this labeled cholesterol pool was
      minimized by repressing liver synthesis of cholesterol with a high cholesterol
      diet. The rate of accumulation of total cholesterol was calculated from the
      increasing amounts of sterol in brain regions at successive time intervals during
      development. Thus, accumulating cholesterol not explained as being newly
      synthesized (radioactive) could be assumed to have come from the circulation.
      Long-Evans rats, ranging in age from birth to 35 days, were injected
      intraperitoneally with [3H]water (0.3-1.0 mCi/g of body weight) and killed 2 h
      later. The brain was dissected into brainstem, cerebellum, and cerebral
      hemispheres, and total lipids were extracted. Cholesterol and its precursors were
      quantified by HPLC. The radioactivity associated with the sterol fractions and
      the specific activity of body water determined from serum were used to calculate
      the absolute amount of newly synthesized sterol. The rates of cholesterol
      synthesis were compared with the rates of accumulation of total cholesterol in
      each brain region. The rate of accumulation of total sterol (cholesterol and
      desmosterol) closely followed that of newly synthesized total sterol in all brain
      regions from the second through the fifth postnatal weeks.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7830085
TI  - Decrease of brain phospholipid synthesis in free-moving n-3 fatty acid deficient
      rats.
AB  - The autoradiographic method with [14C]-docosahexaenoic acid ([14C]22:6 n-3) was
      used to determine whether a diet deficient in n-3 fatty acids, inducing a
      decrease in 22:6 n-3 circulating level, was associated with changes in local
      rates of phospholipid synthesis in the rat brain. As compared with rats fed a
      normal diet (peanut plus rapeseed oil), a n-3 fatty acid deficiency [peanut oil
      group (P group)] induced a generalized decrease (-35 to -76%) of 22:6 n-3
      incorporation rates into phospholipids in all the regions examined. This effect
      was confirmed by using [3H]22:6 n-3 infusion by biochemical analysis and
      quantifications corrected for the contribution of docosahexaenoate derived from
      lipid store recycling to the unesterified pool, taken as the precursor pool for
      phospholipid synthesis in the whole brain. In normal or n-3 fatty acid-deficient
      rats, the values of the brain-to-plasma 22:6 n-3 specific activity ratio (psi)
      were similar (0.03), indicating that a considerable endogenous source of 22:6 n-3
      (97%), likely derived from phospholipid degradation, dilutes the specific
      activity of the tracer coming from plasma. Using the specific activity of 22:6 n
      3 in plasma instead of brain would thus lead to a gross underestimation of the
      rate of phospholipid synthesis. The results also demonstrate that the pattern of
      14C or 3H distribution in brain lipids was not modified by the n-3 fatty acid
      deficient diet. The major lipids labeled were phospholipids, particularly
      phosphatidylethanolamine. Nevertheless, the unesterified 22:6 n-3 concentrations
      in plasma and brain were significantly reduced (eight-and threefold,
      respectively) in the P group. In addition, the proportion of 22:6 n-3 in the
      brain total lipid fraction, total phospholipids, and phosphatidylcholine, 
      ethanolamine, and -serine was significantly decreased in n-3 fatty acid-deficient
      rats. This was partially compensated for by an increase in the 22:5 n-6 level.
      These results are discussed in relation to the limitation of 22:6 n-3 use to
      quantify, by the quantitative autoradiographic method, changes in local rates of
      phospholipid synthesis in rat brain.

PMID- 7830086
TI  - Enzymatic oxidation of dopamine: the role of prostaglandin H synthase.
AB  - An enzyme responsible for the oxidation of dopamine and formation of neuromelanin
      in brain has not been identified. Prostaglandin H synthase is prominent in brain
      and possesses peroxidase activity that may cooxidize dopamine to reactive
      dopamine quinones. This study examined the ability of purified prostaglandin H
      synthase to catalyze the oxidation of dopamine in vitro. Dopamine oxidation was
      determined by monitoring the formation of aminochrome and by examining catechol
      modified residues on protein present in the reaction mixture. Aminochrome was
      formed from dopamine in the presence of prostaglandin H synthase, and the
      reaction rate was dependent on the concentration of substrate and enzyme in the
      reaction mixture. Both arachidonic acid and hydrogen peroxide could serve as
      substrates for the prostaglandin H synthase-catalyzed oxidation of dopamine.
      Indomethacin blocked the reaction when arachidonic acid was used as a substrate,
      but not when hydrogen peroxide was used. Enzymatically oxidized dopamine
      covalently bound to protein, as indicated by the presence of cysteinyl-dopamine
      residues. Binding was significantly reduced in the absence of enzyme or in the
      presence of antioxidants. These results suggest that the peroxidase activity of
      prostaglandin H synthase is responsible for catalyzing the oxidation of dopamine
      to reactive dopamine quinones. It is possible that prostaglandin H synthase is
      responsible for the oxidation of dopamine and formation of neuromelanin in vivo,
      which may have implications for the development of Parkinson's disease.
      Furthermore, drugs such as aspirin that modulate the activity of this enzyme may
      provide a potential therapeutic approach for the prevention of Parkinson's
      disease.

PMID- 7830087
TI  - Swim stress increases the potency of glycine at the N-methyl-D-aspartate receptor
      complex.
AB  - We have previously demonstrated that chronic administration of antidepressants
      results in a reduction in the potency of glycine to displace 5,7
      [3H]dichlorokynurenic acid (5,7-[3H]-DCKA) from the strychnine-insensitive
      glycine recognition site of the NMDA receptor complex. We now report that
      exposure of rats to the forced swim test results in a 56% increase in the potency
      of glycine to displace 5,7-[3H]DCKA from frontal cortical homogenates. These data
      are consistent with the hypothesis that the forced swim test, a preclinical
      screen sensitive to acute administration of antidepressant drugs and NMDA
      receptor antagonists, also results in adaptation of the NMDA receptor complex.
      Moreover, these data lend further support to the hypothesis that glutamatergic
      pathways are involved in the neurobiological response to stress and, potentially,
      in the pathophysiology of depression.

PMID- 7830088
TI  - Increased concentrations of the neurotoxin 3-hydroxykynurenine in the frontal
      cortex of HIV-1-positive patients.
AB  - Human immunodeficiency virus (HIV)-1-associated dementia is a frequent
      consequence of HIV infection and is associated with neuronal deficits. Increased
      concentrations of the kynurenine pathway metabolites 3-hydroxykynurenine (3-HK)
      and quinolinic acid (QA) may contribute to this neuronal damage. We measured 3-HK
      concentrations and the activity of its catabolising enzyme, 3
      hydroxykynureninase, in postmortem brain tissue from eight controls and 32 HIV
      positive patients, including a group that exhibited dementia. 3-HK concentrations
      were significantly increased (over threefold) in the HIV-positive group when
      compared with controls. This increase was greater in those patients with
      dementia, but it was still apparent in the nondemented cases. 3
      Hydroxykynureninase activity was significantly increased in the HIV-infected
      group compared with the control values. The effect was apparent in both
      nondementia and dementia cases, although the latter showed a slightly greater
      increase. The 3-HK content increase is thus unrelated to a reduction in activity
      of this enzyme and is likely to reflect an overall increase in the kynurenic
      metabolic pathway. Elevated levels of the neurotoxin 3-HK may contribute to the
      neuronal deficits underlying HIV-associated dementia.

PMID- 7830089
TI  - [3H]nemonapride and [3H]spiperone label equivalent numbers of D2 and D3 dopamine
      receptors in a range of tissues and under different conditions.
AB  - [3H]Nemonapride and [3H]spiperone are very widely used to study dopaminergic
      systems in vitro and in vivo, but it has been reported that [3H]nemonapride and
      [3H]spiperone give markedly different Bmax values for preparations of D2 dopamine
      receptors from recombinant cell lines or animal tissues. We have used the two
      radioligands in parallel to study a range of dopamine receptors [D2(short),
      D2(long), and D3] in different buffers. Bmax values derived using either
      radioligand differ by an average of < 20%, independent of receptor type or buffer
      conditions. All competition experiments show that the two ligands compete at a
      single site. It seems that [3H]spiperone and [3H]nemonapride do not differentiate
      between different forms or populations of D2-like receptors.

PMID- 7830090
TI  - Novel pharmacological sensitivity of the presynaptic calcium channels controlling
      acetylcholine release in skate electric organ.
AB  - The presynaptic terminals of skate (Raja montagui) electric organ were tested for
      their sensitivity to calcium channel antagonists. Acetylcholine (ACh) release and
      the elevation of intraterminal Ca2+ concentrations triggered by K+ depolarisation
      were studied. ACh release was measured as 3H efflux from slices of organ
      prelabelled with [3H]choline. Depolarisation caused a marked, Ca(2+)-dependent
      increase in 3H efflux that was completely blocked by 100 microM Cd2+ and by 300
      nM omega-conotoxin-MVIIC (MVIIC). Inhibition by MVIIC was concentration dependent
      (IC50 of approximately 20 nM) and reversible. No inhibition was seen with
      nifedipine (5 microM) or the two other peptide antagonists studied: omega
      conotoxin-GVIA (GVIA) at 5 microM and omega-agatoxin-IVA (Aga-IVA) at 1 microM.
      In a "nerve plate" preparation (a presynaptic plexus of nerve fibres, Schwann
      cells, and nerve terminals) changes in intraterminal Ca2+ concentrations were
      measured by microfluorimetry using fluo-3. An increase in fluorescence,
      indicating a rise in the free [Ca2+], rapidly followed K+ depolarisation, and
      this change was restricted to the nerve terminals. This response was insensitive
      to nifedipine (5 microM), GVIA (5 microM), and Aga-IVA (300 nM) but almost
      completely abolished by MVIIC (1 microM). MVIIC inhibition was concentration
      dependent and partially reversible. These results show that the nerve terminals
      in skate electric organ have calcium channels with a pharmacological sensitivity
      that is markedly different from the established L, N, and P types in other
      systems but shares some, but not all, of the features of the recently described Q
      type.

PMID- 7830091
TI  - Gang violence and the street smart nurse.
AB  - Gangs are a serious, growing, and costly problem across the nation. The CHN is at
      increased risk for incidental harm as the result of escalating street gang
      violence. To ensure personal safety, the CHN must be street smart about youth
      gangs. This involves learning about the gang mindset, detecting risk in the
      environment, and maintaining a defensive posture. Because they closely interact
      with high-risk families and youths, CHNs are in a pivotal position to intervene
      successfully in the family and community problem of youth street gangs. It is
      intended that this article will heighten awareness of the seriousness of the gang
      problem. It is further intended to stimulate interest in nursing research in
      these areas: (a) personal street-safety strategies, (b) street-safety guidelines
      for community nursing agencies, (c) stress reduction approaches for the CHN, and
      (d) gang intervention strategies at the family and community levels of practice.
      CHNs must seek opportunity in their role to make a difference in the national
      problem of youth gang violence, for it is a community tragedy that is not going
      to go away.

PMID- 7830092
TI  - Correctional nursing practice.
AB  - This study explored the nature and problems of nursing practice in correctional
      settings using qualitative field research methodology. Data were collected
      through participant observation at three men's state prisons and one city jail
      and included informal interviews and conversations of varying length and depth
      with 40 nursing staff members. Data analysis was accomplished through the
      constant comparative methodology and dimension analysis of grounded theory.
      Custody personnel's recognition, evaluation, and acceptance of judicially
      mandated health care varied across settings and formed a toleration continuum
      with two types (contentious and considered) located at polar ends and a third
      (acknowledged) in a central position. Correctional nurses' conceptions of nursing
      were categorized as limited, expanded, or other-directed. The three types of
      toleration provided differing contexts for correctional nursing practice.
      Interactions between custody and health care staff occurring within each
      toleration scene differentially influenced the degree to which the three
      conceptions of nursing prevailed.

PMID- 7830093
TI  - Sleep and alcohol use in rural old-old women.

PMID- 7830094
TI  - Meeting the health care needs of migrant farmworkers: the experience of the
      Niagara County Migrant Clinic.

PMID- 7830095
TI  - Health education for homeless populations.
AB  - There is little reported in the literature regarding evaluation of health
      education for homeless populations. In a program for health education of the
      homeless in shelters, volunteer instructors, including nurses, provided classes
      on health promotion, prevention, and self-care for homeless clients at 13 urban
      shelters and treatment sites since 1991. Program evaluation was done through a
      survey of clients (N = 1,202) attending classes. Based on analysis of evaluation
      results for 18 months, it was found that 50 volunteer instructors, most of whom
      were nurses, covered 49 health topics in 176 classes. Clients found the classes
      helpful and expressed preferences for future topics (e.g., stress and self
      esteem). Perceived ability to discuss was related to group size and shelter
      composition (women only vs. women and men). Survey results provided feedback for
      program development.

PMID- 7830096
TI  - Parenting and childrearing attitudes among high school students.
AB  - A descriptive study to assess parenting and childrearing attitudes was conducted
      among 502 high school students in a greater metropolitan area in the Southeast.
      The Adult-Adolescent Parenting Inventory (Bavolek, 1984) was used to identify
      students' scores on four constructs associated with abusive parenting:
      inappropriate parental expectations, lack of empathy toward the child, value of
      physical punishment, and parent-child role reversal. Several group differences
      were found by sex, race, grade, and birth order. Ten percent of students scored
      consistently low and could be targeted for education programs to increase
      parenting knowledge and skill.

PMID- 7830097
TI  - Epidemiology of Staphylococcus aureus bacteremia in Denmark.
AB  - The number of Staphylococcus aureus bacteremia cases has increased annually in
      Denmark during the latest decades. This increase has occurred among older
      patients with hospital-acquired bacteremia. Methicillin-resistance, which earlier
      was a property of strains of the 83A phage-complex, has nearly disappeared, while
      the frequency of penicillin-resistance has increased. Today both the phage-type
      pattern and antibiotic resistance are nearly similar for strains from hospital
      acquired and community-acquired cases. In hospitals the frequency of bacteremia
      after postoperative wound infections has decreased, while cases associated with
      intravascular catheters has increased, and these infections are now the most
      common cause of hospital-acquired S. aureus bacteremia. Endocarditis is most
      commonly found in community-acquired cases without an identified primary focus in
      patients between 21-50 years. Also hematogenous osteomyelitis is most common in
      community-acquired cases, but these infections have changed to having a high
      predilection for the vertebral column, and the prevalence of chronic cases has
      decreased.

PMID- 7830098
TI  - Fluconazole, itraconazole and ketoconazole in vitro activity against Candida spp.
AB  - The in vitro activity of fluconazole, itraconazole and ketoconazole against 625
      Candida yeast strains from patients treated at the University Hospital of the
      Canaries, by means of a micromethod of dilution in broth enriched with Yeast
      Nitrogen Base (YNB), and buffered to pH7, has been assessed. Species distribution
      was as follows: Candida albicans (388), Candida tropicalis (84), Candida glabrata
      (84), Candida parapsilosis (69). Our results show 10.0% and 8.8% of C. albicans
      resistant to itraconazole and fluconazole, respectively, and 1.8% resistant to
      ketoconazole; 39.5% of C. tropicalis were resistant to itraconazole, 34.5% to
      fluconazole and 2.4% to ketaconazole. 19.1% of C. glabrata were resistant to
      fluconazole and 13.1% to itraconazole; 4.4% of C. parapsilosis were resistant to
      fluconazole and 1.5% to itraconazole. In general C. tropicalis was the most
      resistant strain and C. parapsilosis the most sensitive. The greatest percentages
      of resistance in vitro were seen with the two triazols.

PMID- 7830099
TI  - Study of lymphotropic targeting and macrofilaricidal activity of a melphalan
      prodrug on the Molinema dessetae model.
AB  - This study deals with the design of a new macrofilaricidal drug derived from
      melphalan and having a lymphotropism to avoid the hepatic first pass effect and
      enhance bioavailability after oral administration. Melphalan was linked to a
      ligand leading to a prodrug called 1,3-dp-melphalan which has structural analogy
      to triglycerides. The Molinema dessetae/Proechimys oris model was used for
      antiparasitic evaluation. Melphalan was macrofilaricidal in vitro against
      Molinema dessetae at 1mM, inactive in vivo after an oral single dose at 164
      mumol/kg while the prodrug 1,3-dp-melphalan was active against adult worms after
      a single dose at 82 mumol/kg. After an oral administration of the prodrug to
      rats, the maximum concentration and the cumulated quantities of melphalan in
      lymph were about 45-fold higher than those observed with the free drug under the
      same conditions. Moreover, the plasma concentration of melphalan was 2-fold
      higher than those observed after the administration of the free drug. These
      results are in favor of lymphotropic targeting as a novel approach to develop new
      orally active macrofilaricides.

PMID- 7830100
TI  - Chlamydia trachomatis genitourinary infections: laboratory diagnosis and
      therapeutic aspects. Evaluation of in vitro and in vivo effectiveness of
      azithromycin.
AB  - Chlamydia trachomatis (C.t.) cell culture represents a sensitive method for the
      diagnosis of chlamydial infection and the only one which makes it possible to
      determine the susceptibility of an isolate to antibiotics so that an appropriate
      drug can be selected for individual treatment. In 11 patients, affected by
      urethroprostatitis and suspected of treatment failure with standard drug
      regimens, either due to lack of compliance with therapy or antibiotic resistance,
      C.t. was isolated in McCoy cell culture from urethral swabs, after prostatic
      massage. The in vitro activity of azithromycin against these isolates and the in
      vivo efficacy of the drug in the patients treated with a single 1 g dose have
      been evaluated. All the C.t. strains tested were susceptible to the action of
      azithromycin (MIC range 0.125-1.0 microgram/ml). Bactericidal values were one
      dilution higher (MBC range 0.25-2.0 microgram/ml). These in vitro results are
      consistent with clinical observations as all the patients treated had negative
      culture at a 4-week follow-up visit.

PMID- 7830101
TI  - Stability of cefodizime in solution and compatibility with other injectable
      drugs.
AB  - The stability of cefodizime in five intravenous infusion fluids (0.9% sodium
      chloride, 5% dextrose in water, 10% dextrose in water, 5% amino acid injection,
      3% polygeline) was studied at room temperature and at 4 degrees C. The
      compatibility of cefodizime with commonly used injectable drugs (ranitidine,
      metoclopramide, folinic acid, furosemide, aminophilline, methylprednisolone,
      betamethasone, hydrocortisone, dexamethasone, ketoprofen, noramidopyrine,
      acetylcysteine, digoxin, diazepam, acetylsalicylic acid, chlorpromazine,
      clonidine, clomipramine) was studied in 0.9% sodium chloride and 5% dextrose at
      room temperature. At intervals during the storage periods (up to 24 hrs at room
      temperature; up to 6 days at 4 degrees C) color, clarity and solution pH were
      examined; cefodizime content was determined by a microbiological method.
      Cefodizime concentrations remained greater than 90% of the initial concentrations
      in all infusion fluids for at least 24 hrs at room temperature and 6 days at 4
      degrees C. No visual changes or appreciable changes in pH were observed for any
      of the solutions. Immediate clouding was observed when chlorpromazine was
      combined with the solution of cefodizime. A color change was observed when
      acetylcysteine was mixed with cefodizime. An increase in pH was noted when
      aminophilline was added to the solution of cefodizime. However, cefodizime
      concentrations remained greater than 90% of the initial concentrations of the
      solutions after mixture with all the tested drugs for at least 24 hrs at room
      temperature.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7830102
TI  - Impact of cefetamet-pivoxil on intestinal microflora: in vivo study.
AB  - In our study we considered the possible interference of cefetamet-pivoxil with
      the intestinal microflora. We used 60 germ-free mice in which an intestinal
      microflora similar to the human one had been implanted. They were treated with
      14.3 mg/Kg/die (standard dose) and a 28.6 mg/kg/die (daily dose) of cefetamet
      pivoxil by oral route. The results obtained in vivo proved that cefetamet-pivoxil
      at therapeutic doses does not influence the normal intestinal microflora.

PMID- 7830103
TI  - A comprehensive multi-institutional study of empiric therapy with flomoxef in
      surgical infections of the digestive organs. The Kyushu Research Group for
      Surgical Infection.
AB  - The effect of flomoxef as empiric therapy for surgical infections of the
      digestive organs was analyzed in 103 patients, most of whom (94.2%) had intra
      abdominal infections. Surgical procedures were performed on 73 patients
      contemporaneously with the flomoxef therapy. Flomoxef is an oxacephem and has a
      potent and broad bactericidal spectrum against aerobes and anaerobes. It provokes
      fewer adverse reactions than latamoxef such as vitamin K deficiency and platelet
      dysfunction. Flomoxef was administered intravenously at a dose 1-4g/day for more
      than 3 days without any other antimicrobial agent. The clinical response was
      classified into 3 groups; cured, improved and failed, and both the cured and
      improved responses were defined as satisfactory. A satisfactory response was
      obtained in 99 patients (96.1%). Regarding bacteriological response, the overall
      eradication rate was 81.3%. Adverse reactions including abnormal laboratory data
      occurred in only two patients. One had abdominal pain, and the other had a mild
      elevation of transaminases, and both were mild and easily reversible. Therefore,
      flomoxef is considered to have the potential of becoming one of the most
      effective agents in empiric therapy for surgical infections of the digestive
      organs.

PMID- 7830104
TI  - Pefloxacin in the treatment of severe infections in gynecological cancer
      patients.
AB  - Infections often complicate the medical or surgical treatment of hospitalized
      cancer patients. In these cases, a broad-spectrum antibiotic treatment is
      necessary before the microbiological results are available. The aim of the
      present study is to verify the efficacy of pefloxacin as empirical antibiotic
      therapy in controlling infectious complications induced by surgery, chemotherapy
      or radiotherapy in female patients with gynecological cancer. To this purpose, 58
      hospitalized patients with gynecologic malignancy and severe infectious
      complications were treated with intravenous pefloxacin at the dosage regimen of
      400 mg every 12 hours. In all, 49 (or 91%) of the 54 evaluable patients were
      cured. The mean duration of successful treatment was 5.9 +/- 2.1 days (ranging 4
      13 days). No side effects or clinical laboratory abnormalities requiring
      reduction or discontinuation of therapy were observed. We conclude that
      pefloxacin may be considered a first choice, broad-spectrum, single antibiotic
      for use in the empirical therapy of infections in gynecological cancer patients.

PMID- 7830105
TI  - A phase II study of advanced colorectal cancer patients treated with combination
      5-fluorouracil plus leucovorin and subcutaneous interleukin-2 plus alpha
      interferon.
AB  - Twenty-one patients with advanced, pretreated colorectal cancer in disease
      progression were entered in a phase II study to investigate the use of 5
      fluorouracil (5FU) + leucovorin with subcutaneous Interleukin-2 + alpha
      interferon (alpha-IFN). Eighteen of these patients were evaluable for response to
      treatment: 1 partial response (PR) (duration 8 months), 9 stable disease (SD)
      (median duration of 6.5 months, range 2-15) and 8 progressive disease (PD). The
      PR patient survived for 15 months, the SD patients for a median of 11 months and
      8 months for PD patients. Toxicity evaluated in the 21 patients reached grade 4
      for mucositis in two cases. Grade 3 toxicity was observed more frequently for
      fever (52.3%) and diarrhea (33.3%) and was most probably the result of the
      combined side-effect of chemotherapy and the biological response modifiers
      (BRMs). Treatment was, for the most part, carried out on an out-patient basis as
      originally planned. In 15 patients tests were carried out to verify whether any
      immuno-activation had taken place. Significant increases were found during the
      course of therapy regarding cluster of differentiation activation (HLA-DR, CD71,
      CS25). Different curves were observed during the course of treatment with respect
      to the CD8 value, which proved higher in SD patients than in PD patients. Our
      study would seem to suggest that the addition of BRMs to 5FU + leucovorin could
      increase survival. The next step, however, must be to determine lower doses of IL
      2 for subcutaneous administration in order to reduce toxicity but maintain the
      same immunostimulation.

PMID- 7830106
TI  - Does substitution of surgery with induction chemotherapy preserve organ function
      in inoperable head and neck cancer? A retrospective analysis of 73 cases.
AB  - From August, 1984 until May, 1991, 154 patients with locally advanced head and
      neck cancer were treated with 3 cycles of platinum-containing induction
      chemotherapy followed by definitive radiotherapy. Among them, there were 32
      patients with cancer of oropharynx or hypopharynx and 41 patients with cancer of
      larynx, who were treated with this combined approach with the intention of
      preserving the involved organ. After the completion of chemotherapy 5 (16%)
      patients with pharyngeal tumors achieved a complete response (CR) and 14 (44%) a
      partial response (PR). After the completion of radiotherapy the CR rate was
      increased to 38%. After induction chemotherapy 7 (17%) of the 41 patients with
      cancer of the larynx achieved a CR and 25 (61%) a PR. The CR rate was tripled
      (68%) following radiotherapy and salvage surgery. So far, 8 complete responders
      with pharyngeal and 6 with laryngeal tumors relapsed mainly locoregionally. With
      a minimum follow-up of 22 months, median time to progression was 8 months for
      patients with cancer of the pharynx and 13 months for patients with cancer of the
      larynx. Median survival for these two groups of patients was 13 and 24 months
      respectively. In patients with locally advanced cancer of the oropharynx,
      hypopharynx or larynx induction chemotherapy followed by radiotherapy may delay
      in many or even omit in a few patients the necessity of radical surgery without
      compromising survival.

PMID- 7830107
TI  - Scintimammography: magic bullet or false promise?

PMID- 7830108
TI  - Reproducibility of SPECT measurement of benzodiazepine receptors in human brain
      with iodine-123-iomazenil.
AB  - Iodine-123-iomazenil is a SPECT radiotracer used to image and quantify
      benzodiazepine receptors. The reproducibility of the measurement of
      benzodiazepine receptors in human brain with [123I]iomazenil and SPECT was
      investigated with a test/retest paradigm. METHODS: Six subjects underwent two
      experiments during a 1-wk interval. Iodine-123-iomazenil was injected as a single
      bolus (12 mCi). The time-activity curves of the tracer in the arterial plasma
      were measured and corrected for metabolites. Regional time-activity curves of
      five brain regions were measured with the CERASPECT camera for 145 min
      postinjection with serial 2-min acquisitions. Data were analyzed using three
      kinetic models that included a two-compartment model, an unconstrained three
      compartment model and a three-compartment model with a constraint on the
      nondisplaceable compartment. RESULTS: The results from the various analyses and
      fitting strategies were compared. The variability (average absolute difference
      between test and retest, expressed as a percentage of the mean of both
      measurements) was 10% to 17%, depending on the outcome measure and the fitting
      procedure. The most reproducible outcome measure was the regional tracer
      distribution volume relative to the total arterial concentration (VT'). VT'
      showed an average regional variability of 10% +/- 2%, with an intraclass
      correlation coefficient of 0.81. CONCLUSION: SPECT measurement of regional
      [123I]iomazenil VT' is reproducible and reliable. The use of regional ratios
      results in a significant loss of information.

PMID- 7830109
TI  - Direct comparison of fluorine-18-FDG SPECT, fluorine-18-FDG PET and rest thallium
      201 SPECT for detection of myocardial viability.
AB  - Twenty consecutive patients were evaluated for presumptive myocardial viability
      using rest TI-SPECT, FDG-PET and FDG-SPECT. The FDG studies were performed after
      rest TI-SPECT to guide intervention or medical management. METHODS: Twenty
      patients with proven coronary artery disease, either known or suspected to have
      previous myocardial infarction and persistent perfusion defects shown by rest
      reinjection TI-SPECT, underwent FDG-PET and subsequent FDG-SPECT with a three
      detector SPECT camera. FDG-PET and SPECT images were compared by five observers
      to determine if any fixed thallium segments were visualized by either FDG imaging
      method. RESULTS: Thirteen of 60 fixed segments were shown probably viable by FDG
      SPECT (8 of 20 patients) and 14 of 60 by FDG PET (7 of 20 patients). Two patients
      had fixed thallium segments found probably viable with FDG by SPECT alone and one
      by PET alone. CONCLUSION: FDG is shown to provide additional information about
      myocardial viability. Both SPECT, using a three-detector camera, and PET with a
      specialized instrument are equally effective for imaging FDG in this application.

PMID- 7830110
TI  - Relationship between reverse redistribution on planar thallium scintigraphy and
      regional myocardial viability: a correlative PET study.
AB  - The purpose of this study was to assess myocardial metabolic activity in the area
      of reverse redistribution and determine the prognostic value of reverse
      redistribution and PET imaging. Reverse redistribution is thought to be a
      manifestation of reperfusion therapy and associated with a favorable clinical
      outcome. Preliminary observations from the Thrombolysis and Myocardial Infarction
      (TIMI) trial suggest that reverse redistribution is associated with higher
      incidence of future cardiac events. METHODS: Thirty-two patients with chronic
      coronary artery disease and reverse redistribution on planar thallium
      scintigraphy had PET 13NH3/18FDG imaging. Radionuclide angiocardiography was
      performed in 23 patients. RESULTS: Fifty segments showed reverse redistribution
      on planar thallium images; 19 segments had normal 13NH3 and 18FDG uptake and 17
      were ischemic by PET criteria. Thus, a total of 72% (36 of 50) of reverse
      redistribution segments were PET viable. Sixty-one percent of segments with
      abnormal regional wall motion and reverse redistribution were PET scar. On follow
      up, 31% (10/32) had a cardiac event (nine unstable angina and one myocardial
      infarction). Fifty percent of patients (5/10) with cardiac events had severe
      reverse redistribution and PET viability versus 9% (2/22) without cardiac events
      (p = 0.01). CONCLUSIONS: The majority of thallium reverse redistribution segments
      was PET viable as judged by 18FDG uptake. Viability in areas of reverse
      redistribution is not inferred by regional wall motion analysis. Regional PET
      viability identifies patients with reverse redistribution with a higher
      likelihood of future cardiovascular events. PET viability assessment may be
      helpful with the impact of reverse redistribution on planar thallium
      scintigraphy.

PMID- 7830111
TI  - Artifactual inhomogeneities in myocardial PET and SPECT scans in normal subjects.
AB  - It has been well established that PET and SPECT scans of human myocardium are
      subject to partial volume related effects, which can cause artifactual regional
      variations in activity around the myocardium. This study investigated the sources
      and magnitude of such artifactual inhomogeneity in subjects with normal cardiac
      function. METHOD: Using multi-slice, gated MRI scans from 9 normal subjects, we
      examined separately the influences on measured activity of wall motion, axial
      resolution and the relationship between wall thickness and in-plane resolution.
      RESULTS: Two patterns of artifactual inhomogeneity were found: a depression in
      activity at the antero-apex and an elevation in activity in the free wall
      compared with the septum. Thus, in ungated PET images the true apical/septal
      ratio was artifactually reduced by a factor of 0.89 (0.92 for SPECT), while the
      true free wall/septal ratio was enhanced by a factor of 1.12 (1.19 for SPECT).
      Gating improved uniformity in end-systolic (ES) images but degraded uniformity in
      end-diastolic (ED) images. With gating, the true PET apical/septal ratio was
      artifactually reduced by only 0.97 at ES, and 0.82 at ED. Similar behavior was
      found for SPECT. Improvements in axial resolution were found to have little
      effect on artifactual variations. CONCLUSION: We find that the relationship
      between in-plane resolution and wall thickness, but not axial resolution, is of
      prime importance in determining the degree of artifactual inhomogeneity in
      ungated scans of normal human myocardium. Gating improved ES but degraded ED
      homogeneity.

PMID- 7830112
TI  - Impaired left ventricular diastolic filling in patients with acromegaly:
      assessment with radionuclide angiography.
AB  - Acromegaly is associated with increased cardiac morbidity and mortality, but it
      is not clear whether this is the result of a specific disease of heart muscle or
      of increased incidence of hypertension. METHODS: Twenty-six patients with
      acromegaly (11 male and 15 female, mean age 45 +/- 13 yr) and 15 and 12 age- and
      sex-matched normal controls underwent high temporal resolution radionuclide
      angiography and two-dimensional echocardiography at rest. RESULTS: Normal
      controls and patients with acromegaly did not differ with respect to heart rate,
      ejection fraction, time to end systole, peak ejection rate (PER) and time to PER.
      In contrast, peak filling rate (PFR), normalized to end diastolic volume (EDV),
      or stroke volume (SV), or expressed as the ratio of PFR-to-PER was reduced (p <
      0.01), time to PFR (TPFR) was prolonged (p < 0.01), and echocardiographic left
      ventricular mass index was higher (p < 0.001) in patients with acromegaly
      compared to normals. Patients with acromegaly were divided in normotensives
      (group 1, n = 17) and hypertensives (group 2, n = 9). Although left ventricular
      mass index was significantly (p < 0.01) higher in group 2 compared to group 1,
      PFR and time to PFR were not different between the two groups of acromegalic
      patients. In the entire group of patients with acromegaly significant
      relationships between left ventricular mass index and EDV/s (r = -0.56, p <
      0.01), SV/s (r = -0.73, p < 0.001), and PFR/PER (r = -0.61, p < 0.001) were
      observed. CONCLUSION: Patients with acromegaly have impaired left ventricular
      diastolic filling at rest related to greater left ventricular mass index even in
      the absence of systemic hypertension.

PMID- 7830113
TI  - Institute of Medicine urges construction of new accelerator.

PMID- 7830114
TI  - Primary lung cancer SPECT imaging with pentavalent technetium-99m-DMSA.
AB  - To assess the clinical role of 99mTc(V)-DMSA in primary lung cancers, SPECT
      imaging was performed on 31 patients with suspected lung cancer. METHODS: Planar
      and SPECT images were obtained at 3 to 4 hr after intravenous injection of
      approximately 555 MBq 99mTc(V)-DMSA. Two uptake ratios (the maximum counts/pixel
      in the lesion to the average counts in normal tissue) were calculated. RESULTS:
      Various types of primary lung cancers (adenocarcinoma, squamous-cell carcinoma,
      small-cell carcinoma, large-cell carcinoma and bronchial carcinoid tumor) were
      imaged by 99mTc(V)-DMSA SPECT. Approximately 90% of the lung carcinomas showed
      increased uptake and were clearly demonstrated by SPECT images. Four cases
      incidentally revealed osseous metastatic lesion. Three benign lesions did not
      show increased uptake. Three cases were false-negative and there were no false
      positive cases for the primary lesions. CONCLUSION: Technetium-99m(V)-DMSA SPECT
      images demonstrated approximately 90% of the primary lung cancers. Uptake ratios
      were higher in squamous-cell carcinomas than adenocarcinomas. Evaluation of
      mediastinal tumor extension and nodal metastatic lesion was very difficult by
      high blood-pool activity in the major cardiovascular structures due to slow blood
      pool clearance. However, 99mTc(V)-DMSA SPECT imaging was very useful for
      detecting primary lung cancers and metastatic lesions to the osseous structures.

PMID- 7830115
TI  - Tissue characterization in nuclear oncology: its time has come.

PMID- 7830116
TI  - Detection of lymph node metastases of squamous-cell cancer of the head and neck
      with FDG-PET and MRI.
AB  - The uptake of 2-deoxy-2-[18F]fluoro-D-glucose (FDG) in neck lymph nodes of twelve
      patients with a squamous-cell carcinoma of the oral cavity was studied with PET
      in order to detect and locate lymphogenic metastases. METHODS: The results of FDG
      PET imaging were compared with clinical, MRI and histopathologic findings.
      Standardized uptake values (SUV) were also calculated. RESULTS: A sensitivity of
      91% and a specificity of 88% were calculated for FDG-PET. In contrast, a
      sensitivity of 36% and a specificity of 94% were calculated for MRI. Calculated
      SUVs for reactive lymph nodes, metastatic lymph nodes and the primary tumor were
      undifferentiated. CONCLUSION: Using FDG-PET, lymph node metastases of squamous
      cell carcinomas of the oral cavity can be visualized with a high sensitivity and
      specificity. FDG-PET can be an improvement in the evaluation of the neck.

PMID- 7830117
TI  - Radioiodine therapy of the autonomous thyroid nodule in patients with or without
      visible extranodular activity.
AB  - Patients with an autonomously functioning thyroid nodule (ATN) may be present
      with various clinical, biochemical and scintigraphic features. To optimize 131I
      dose planning and treatment timing in these patients, relationships between
      dosimetric data and clinical follow-up events must be established. METHODS: We
      retrospectively reviewed the records of 88 patients who received 131I (intended
      dose of 80 Gy) for an ATN, of whom 39 had evidence of extranodular activity (ENA)
      and 76 presented with overt thyrotoxicosis. In all of the patients, dosage
      calculation was monitored to estimate precisely both beta and gamma absorbed
      doses received by the ATN and the nodule-free lobe. The mean duration of follow
      up was 75 mo (max 180) and always included biochemical thyroid tests. Finally, we
      compared the dosimetric profiles of four dosage schemes which had been normalized
      by simulation to ensure that the same absorbed dose threshold value was always
      delivered to the ATN. RESULTS: About 75% of the patients were cured at 6 mo for a
      mean 305 MBq administered. The absorbed doses delivered to the nodule-free lobe
      ranged from 12% (no ENA) to 86% (ENA) of the values delivered to the ATN, mainly
      in the form of beta irradiation. Life-table estimates for hypothyroidism and
      death were 9.6% and 22% at 75 mo, respectively. Hypothyroidism mainly developed
      in patients with nonsuppressed TSH levels but regardless of ENA, which often
      accounted for multifocal disease. CONCLUSION: We suggest that fixed doses
      bordering on 370 MBq are advizable in younger individuals and in patients with
      mild thyrotoxocosis, while 555 MBq-740 MBq can be administered in other patients
      and that ENA indicates multifocal autonomy in patients with toxic ATN and is a
      further indication for radioiodine treatment which should be begun as soon as
      possible to avoid the development of cardiac complications.

PMID- 7830118
TI  - Clinical comparison of technetium-99m-EC, technetium-99m-MAG3 and iodine-131-OIH
      in renal disorders.
AB  - Technetium-99m-ethylenedicysteine has recently been developed for renal function
      studies. The pharmacokinetics of 99mTc-EC were studied by constant infusion
      technique and compared with 99mTc-MAG3 and 131I-OIH in 11 patients with various
      renal disorders. METHODS: After giving a 7.4 MBq 131I-OIH and 90-110 MBq 99mTc-EC
      or 99mTc-MAG3 bolus, a constant infusion (1MBq/ml 99mTc-agent and 0.07 MBq/m 131I
      OIH was started. Sixteen blood and five urine samples were obtained over three
      hr. RESULTS: The renal clearance of 99mTc-EC was higher than that of 99mTc-MAG3.
      The 99mTc-EC/OIH and 99mTc-MAG3/OIH ratios were 0.75 +/- 0.05 and 0.55 +/- 0.10
      (p = 0.00087), respectively. The distribution volume of 99mTc-EC was also higher
      than that of 99mTc-MAG3 (15722 +/- 4644 and 9509 +/- 2788 ml/1.73m2,
      respectively; p = 0.072). The 99mTc-EC/OIH and 99mTc-MAG3/OIH distribution volume
      ratios were 1.03 +/- 0.14 and 0.55 +/- 0.10, respectively (p = 0.0003). The 60
      min excretion values of 99mTc-EC and 99mTc-MAG3 were compared to that of OIH. The
      99mTc-EC/OIH and 99mTc-MAG3/OIH excretion ratios were 0.96 +/- 0.06 and 1.07 +/-
      0.10, respectively (p = 0.162). The protein binding of 99mTc-EC and OIH were
      found to be 34% +/- 4 and 66% +/- 5, respectively (p < 0.0001). The red cell
      binding of 99mTc-EC was negligible (3% +/- 1.2) in comparison to OIH (27% +/- 3;
      p < 0.0001). CONCLUSION: This limited study demonstrates the pharmacokinetic and
      renal clearance properties of 99mTc-EC. This agent has good potential for renal
      function evaluation.

PMID- 7830119
TI  - Value of fluorine-18-fluorodeoxyglucose and thallium-201 in the detection of
      pancreatic cancer.
AB  - This study compares the diagnostic value of 18F-FDG PET imaging and 201TI-SPECT
      imaging in patients with pancreatic cancer. METHODS: Twenty-five patients with
      histologically-proven pancreatic cancer were studied. Following PET transmission
      scanning, 3 mCi of 201TI were administered after patients had fasted overnight.
      Thallium-201-SPECT images were obtained 15 min later. Immediately after 201TI
      SPECT imaging, 4 mCi of FDG were administered and PET images were obtained 60 min
      later. The PET and SPECT images were compared qualitatively and quantitatively.
      For quantitative analysis, 10 x 10 mm2 regions of interest (ROIs) were selected
      in areas of the tumor showing the highest tracer accumulation and in the normal
      pancreas. The tumor to nontumor activity ratio (T/N ratio) was calculated.
      RESULTS: Although both techniques delineated focal lesions with an increase in
      tracer accumulation in 16 patients, PET identified eight additional patients in
      whom 201TI-SPECT images did not visualize any lesion. Thus, FDG-PET provided
      significantly higher sensitivity (96%) than 201TI-SPECT (64%). Among the patients
      showing increased tracer accumulation, the T/N ratio was significantly higher
      with FDG-PET (3.24 +/- 1.27) than with 201TI-SPECT (1.77 +/- 0.37) (p < 0.0001).
      CONCLUSION: We conclude that FDG-PET has a larger clinical value for noninvasive
      detection of pancreatic cancer than 201TI-SPECT. If a PET camera is available,
      FDG-PET is considered to be the method of choice for the evaluation of patients
      with suspected pancreatic cancer.

PMID- 7830120
TI  - Primary breast lymphoma detected with SPECT using gallium-67-citrate.
AB  - Breast involvement by malignant lymphoma either as a primary site or as a
      secondary site from lymphoma elsewhere is rare. Primary breast lymphoma (PBL)
      accounts for only a small percentage of total malignant lymphoma involving the
      breast. The incidence of PBL varies from 0.004% to 0.5%. We present a case of PBL
      which was well demonstrated on total-body imaging as well as SPECT using 67Ga
      citrate.

PMID- 7830121
TI  - Brain SPECT imaging for laminar heterotopia.
AB  - Brain perfusion SPECT was performed in an epileptic patient with a rare form of
      diffuse subcortical laminar heterotopia using 99mTc-HMPAO. MRI demonstrated
      generalized laminar heterotopia underlying the cortical mantle. Interictal SPECT
      imaging revealed identical or increased perfusion of the laminar heterotopia as
      compared with that of the overlying cortical mantle. Moreover, SPECT revealed low
      perfusion in the left temporal lobe that agreed with the seizure type of complex
      partial seizures and the EEG finding of frequent generalized spike-wave complexes
      with a slight left-sided dominance. Brain SPECT imaging may be useful for
      appropriate diagnosis of gray matter heterotopia and for detection of
      functionally focal abnormality associated with epilepsy.

PMID- 7830122
TI  - Rapid washout of technetium-99m-MIBI from a large parathyroid adenoma.
AB  - We report a case of rapid 99mTc-methoxyisobutylisonitrile (MIBI) clearance from a
      parathyroid adenoma. A double-phase 99mTc-MIBI parathyroid scintigraphy was
      performed on a 62-yr-old female evaluated for primary hyperparathyroidism. A
      large parathyroid adenoma was visualized caudal to the left lobe of the thyroid
      gland with an unusually rapid washout of the tracer from tumor tissue. Histologic
      tissue examination confirmed the presence of a parathyroid adenoma and the
      absence of oxyphil cells. Care should be taken in interpretation of 99mTc-MIBI
      parathyroid scintigrams because some adenomas can present a rapid release of the
      radiotracer in a double-phase study. Technetium-99m-MIBI retention could be
      related to the number of mitochondria-rich cells in parathyroid adenomas or to
      hyperplasia.

PMID- 7830123
TI  - Fourier phase analysis of first-pass data: noninvasive detection of pulmonary
      sequestration.
AB  - Nuclear medicine Fourier phase analysis of first-pass data was used to evaluate
      blood flow to cystic lung masses in two children suspected of having pulmonary
      sequestrations. In both cases, the Fourier images provided a rapid, noninvasive,
      inexpensive analysis of the blood supply to the masses and permitted
      identification of the masses as pulmonary sequestrations. The analysis does not
      depend on the location of the mass and demonstrates the location of systemic
      rather than pulmonic arterial blood supply to the mass. In one case, Fourier
      analysis identified a second source of systemic blood supply not visible with
      other imaging modalities. Preoperative assessment of a cystic lung mass using
      Fourier analysis enables noninvasive classification of the mass as a pulmonary
      sequestration with systemic blood supply and aids the surgeon in resection.

PMID- 7830124
TI  - Bone scan in tumor-induced osteomalacia.
AB  - A 66-yr-old female was admitted with a 3-yr history of generalized bone pain and
      nasal obstruction. CT and MRI of the head revealed a large nasal mass. A whole
      body bone scan revealed multifocal lesions of increased activity. Surgical
      removal of the nasal tumor revealed hemangiopericytoma. The patient improved
      clinically and a repeat bone scan 10 mo after surgery revealed markedly improved
      findings.

PMID- 7830125
TI  - Unexpected bone marrow uptake of thallium-201 in nonsecretory myeloma.
AB  - A 43-yr-old man was referred for any possible parathyroid abnormality that could
      explain his hypercalcemia and slightly increased parathormone levels. The
      thallium-technetium scan showed a diffuse abnormal thallium uptake incidentally
      in the bone marrow, otherwise parathyroid scan appearance was normal. He had an
      essentially normal bone scan, although subsequent nanocolloid scintigraphy
      demonstrated bone marrow expansion. Further investigations, including a bone
      marrow aspiration biopsy, confirmed the diagnosis of nonsecretory myeloma. This
      finding suggests that 201Tl imaging can be a useful tool to investigate those
      patients suffering from similar myeloid disorders causing bone marrow
      hyperplasia.

PMID- 7830126
TI  - In vitro comparison of cell proliferation kinetics and uptake of tritiated
      fluorodeoxyglucose and L-methionine in squamous-cell carcinoma of the head and
      neck.
AB  - Estimation of tumor proliferative activity is important for the optimal
      management of head and neck cancer. Noninvasive metabolic imaging with PET may
      complement currently used cytopathologic methods to study tumor proliferation.
      METHODS: Fluorodeoxyglucose (FDG) and L-methionine (MET) were studied for their
      potential to assess in vitro the growth characteristics of three squamous-cell
      carcinoma (SCC) cell lines established recently in patients with head and neck
      cancer. A time-course uptake of tritiated FDG and MET was measured over the
      complete growth cycle of one rapidly growing (UT-SCC-5) and two relatively slower
      growing (UT-SCC-1A and UT-SCC-9) cell lines. DNA flow cytometry was used for
      assessment of proliferative activity. RESULTS: There was a strong linear
      relationship for both FDG and MET uptake versus the viable cell number although
      absolute MET uptake was consistently lower than that of FDG in the exponential
      and plateau phases of growth (p < 0.01), leading MET to underestimate cell
      number. The pattern of MET uptake followed the flow cytometric changes in the
      proliferation index (% of S + G2/M cells) in two of three cases (UT-SCC-1A and UT
      SCC-5) while a similar, although clearly weaker, relationship was seen with FDG
      and flow cytometry findings in only one case (UT-SCC-5). CONCLUSION: In these
      three human SCC cell lines assessed in vitro, FDG is a better marker of cell
      viability than MET, whereas MET is superior for estimating proliferative
      activity. Extrapolations of these in vitro data to the interpretation of PET
      images should be made with caution since tumors may have confounding factors that
      may affect in vivo tracer uptake.

PMID- 7830127
TI  - Radioprotection against biological effects of internal radionuclides in vivo by S
      (2-aminoethyl)isothiouronium bromide hydrobromide (AET).
AB  - Radionuclides employed in diagnostic and therapeutic nuclear medicine impart
      radiation energy to tissue over an extended period of time, which depends on the
      physical half-life and the biological properties of the radiochemical employed.
      It is therefore important to examine the capacity of chemical radioprotectors to
      mitigate damage caused by chronic irradiation by incorporated radionuclides.
      METHODS: Spermatogenesis in mouse testis is used as the experimental model, and
      spermatogonial cell survival as measured by testicular spermhead count is the
      biological end point. The capacity of S-(2-aminoethyl)isothiouronium bromide
      hydrobromide (AET) to mitigate radiation damage caused by chronic irradiation by
      the radiochemicals 125IUdR, H125IPDM and 210Po-citrate, is investigated. RESULTS:
      The radioprotection provided by AET is substantial and similar for both of the
      radioiodinated compounds with dose modification factors (DMF) of 4.0 +/- 1.2 for
      125IUdR and 3.4 +/- 0.4 for H125IPDM. In contrast, the damage caused by 210Po
      alpha particles is protected against to a lesser degree (DMF = 2.4 +/- 0.5).
      CONCLUSION: The present radioprotection data for AET, in conjunction with our
      earlier findings for the chemical protectors cysteamine and vitamin C in the same
      experimental model, suggest that such compounds may be clinically useful as
      mitigating agents against biological damage caused by incorporated radionuclides.
      The observed DMFs for AET also support our earlier premise that the mechanism by
      which DNA-incorporated Auger emitters impart biological damage is primarily
      radical mediated, and hence indirect in nature.

PMID- 7830128
TI  - Nuclear renal scan offers hope to transplant patient.

PMID- 7830129
TI  - The transition from technegas to pertechnegas.
AB  - We set out to determine the oxygen concentration of the argon-oxygen mixture in
      the technegas generator where technegas-like behavior changes to pertechnegas
      like behavior which allows [99mTc]pertechnetate to enter the solution. METHODS:
      We prepared radioaerosols analogous to technegas and pertechnegas, with oxygen
      concentrations between 0% and 5%. They then were examined by thin-layer
      chromatography using saline as a solvent to measure the amount of
      [99mTc]pertechnetate moving with the solvent front as a function of oxygen
      concentration. RESULTS: The amount of mobile pertechnetate markedly increased
      when the radioaerosols were created in an atmosphere containing between 0.1% and
      0.2% oxygen. The transition from technegas-like to pertechnegas-like behavior
      occurs when the oxygen-argon gas mixture contains lower concentrations of oxygen
      than those used in the preparation of pertechnegas. CONCLUSION: Argon intended
      for the preparation of technegas should contain no more than 0.1% oxygen.

PMID- 7830130
TI  - Effect of N-0861, a selective adenosine A1 receptor antagonist, on pharmacologic
      stress imaging with adenosine.
AB  - N6-endonorboman-2-yl-9-methyladenine (N-0861) is a drug which inhibits the A1
      adenosine receptor subtype. One proposed use for N-0861 is to eliminate A1
      receptor-mediated side effects such as A-V heart block and possibly angina in
      patients undergoing pharmacologic stress with adenosine. The goal of this study
      was to determine whether N-0861 has any crossover effect on the A2 vasodilatory
      action of adenosine or on 201TI uptake which would adversely affect imaging of
      coronary stenoses. METHODS: In eight dogs with critical left anterior descending
      (LAD) stenoses, we compared the hemodynamic response to intravenous adenosine
      (250 micrograms/kg/min) before and after N-0861 administration. LAD and left
      circumflex (LCx) coronary flows were measured ultrasonically and regional blood
      flow was assessed using microspheres. Thallium-201 (18.5-37.0 MBq) was injected
      during adenosine hyperemia while N-0861 was present. Imaging of heart slices was
      performed and defect magnitude was calculated as LAD:LCx count ratios from
      regions of interest (ROIs) on images. Regional 201Tl activity and microsphere
      flow were determined by gamma well counting. RESULTS: There was no change in mean
      heart rate, arterial and left atrial pressures, +dP/dt, and ultrasonically
      measured LAD and LCx coronary flows upon N-0861 administration. In addition,
      adenosine evoked a similar hemodynamic response after N-0861. There was also no
      change in coronary flow in the critically stenotic LAD but LCx flow tripled to
      106 +/- 14 ml/min (p < 0.01). CONCLUSION: These data indicate that N-0861
      pretreatment does not adversely affect adenosine A2 receptor-mediated
      vasodilation and has no effect on the detection of a critical coronary stenosis
      by 201Tl imaging. Thus, the pretreatment strategy may prove useful for the
      elimination of A1 receptor-mediated side effects during pharmacologic stress
      imaging with adenosine.

PMID- 7830131
TI  - New directions in pharmacologic stress imaging.

PMID- 7830132
TI  - Evaluation of SPECT quantification of radiopharmaceutical distribution in canine
      myocardium.
AB  - This study evaluates the quantitative accuracy of SPECT for in vivo distributions
      of 99mTc radiopharmaceuticals using fanbeam (FB) and parallel-beam (PB)
      collimators and compares uniform and nonuniform attenuation correction methods in
      terms of quantitative accuracy. METHODS: SPECT quantification of canine
      myocardial radioactivity was performed followed by well counter measurements of
      extracted myocardial tissue samples. Transmission scans using a line source and
      an FB collimator were performed to generate nonuniform attenuation maps of the
      canine thorax. Emission scans with two energy windows were acquired. Images were
      reconstructed using a filtered backprojection algorithm, with a dual-window
      scatter subtraction combined with either no attenuation compensation or single
      iteration Chang attenuation compensation based on an uniform attenuation map (mu
      = 0.152 cm-1) or the nonuniform transmission map. RESULTS: The measured mean
      counts from the SPECT images were converted to radionuclide concentrations
      (MBq/g) using a standard source calibration and were compared with those obtained
      using the well counter. CONCLUSION: The experimental results demonstrate that,
      compared with well counter values, the in vivo distributions of 99mTc were most
      accurately determined in FB and PB SPECT reconstructions with nonuniform
      attenuation compensation, under-estimated without attenuation compensation and
      overestimated with uniform attenuation compensation.

PMID- 7830133
TI  - Variability and reproducibility of rubidium-82 kinetic parameters in the
      myocardium of the anesthetized canine.
AB  - Kinetic analysis of 82Rb dynamic PET data produces quantitative measures which
      could be used to evaluate ischemic heart disease. These measures have the
      potential to generate objective comparisons of different patients or the same
      patient at different times. To achieve this potential, it is essential to
      determine the variability and reproducibility of the kinetic parameters. METHODS:
      A total of 48 82Rb dynamic PET datasets were acquired from two pure bred beagles.
      Each animal underwent eight 82Rb PET studies with essentially the same protocol
      for three successive weeks. Data were acquired with the Donner 600-Crystal
      Positron Tomograph (PET600). In each week, single-slice dynamic 82Rb PET datasets
      were collected with the animal at rest at three different gantry positions
      separated by 5 mm. Additional dataset were collected after dipyridamole infusion
      and after administration of aminophylline to induce a return to rest. A two
      compartment kinetic model with correction for myocardial vasculature and
      spillover from the left ventricular blood pool was used to analyze the dynamic
      datasets. Model parameters for uptake (k1), washout (k2) and vascular fraction
      (fv) were estimated in 11-14 myocardial regions of interest (ROIs) using a
      weighted least-squares criterion. Statistical fluctuation due to the PET
      acquisition process was minimized by using a relatively high 82Rb dose (about 30
      mCi) to take advantage of the high count rate capacity of the PET600. RESULTS:
      The variation in mean k1, where the mean is taken over the myocardial ROIs was
      10%-20% (Dog 1) and 15%-50% (Dog 2) among the rest studies conducted on the same
      date. Similar variation was evident in comparing studies in the same animal for
      different weeks. CONCLUSION: Spatial and temporal variation in estimates of the
      uptake rate (k1) of 82Rb in the resting myocardium of the anesthetized canine are
      small in relation to the functional increase in k1 following dipyridamole
      infusion.

PMID- 7830134
TI  - A modeling method to improve quantitation of fluorodeoxyglucose uptake in
      heterogeneous tumor tissue.
AB  - The standard approach for evaluating FDG-PET kinetic studies is based upon an
      assumption that tissue within a representative region of interest (ROI) is
      relatively homogeneous in terms of FDG kinetics. In neoplasms and other disease
      states, tissue within an ROI may be grossly heterogeneous, due to adjacent
      infarcted tissue and other causes. We have developed a method employing two ROIs
      (one over the tumor and another over a "reference region") to deal with this
      level of heterogeneity. METHODS: The method is based on the regular FDG model but
      consists of six variable parameters (6P model) which uses the kinetics in the
      reference region to account for the normal tissue within the tumor ROI, so that
      the kinetic data only associated with the tumor can be estimated. Monte Carlo
      simulations and human PET FDG studies were used to analyze the performance of the
      6P model. RESULTS: The narrower 95% confidence intervals of parameter estimates,
      which centered at the true tumor rate constants, and the smaller correlation
      matrix of the 6P model showed the better performance of the 6P model compared to
      the standard "homogeneous" four-parameter FDG model. Computer simulations further
      showed that the 6P model can accurately estimate the microparameters (rate
      constants: K1* (ml/min/g), k2* (min-1), k3* (min-1), k4* (min-1)) and the
      macroparameter (K (ml/min/g)) of tumor cells regardless of the percent weight of
      tumor cells in the lesions. CONCLUSIONS: The new method can produce more reliable
      and accurate estimates of tumor glucose metabolic rates with dynamic PET FDG
      studies.

PMID- 7830135
TI  - Commentary--Part 2. The nuclear medicine industry: strategies for survival.

PMID- 7830136
TI  - Improved signal-to-noise in PET activation studies using switched paradigms.
AB  - PET activation studies employing the autoradiographic technique and 15O-water or
      15O-butanol use the difference between images acquired under baseline conditions
      and during activation to detect focal changes in cerebral blood flow which occur
      upon stimulus presentation. Typically, the activating task or baseline conditions
      are maintained throughout the entire imaging period. Simulations of the kinetics
      of these freely diffusible tracers suggest there may be an advantage to switching
      between activation and baseline conditions during the course of the study which
      results in images which maximize the difference signal rather than seeking to
      quantitate blood flow. We examine the potential of these switched protocols to
      increase signal-to-noise (S/N) in PET activation studies. METHODS: We examined
      S/N in activation studies using both-standard and switched paradigms with a
      simple switched protocol and dynamic three-dimensional PET data from human
      subjects. With tracer kinetic simulations, we investigated the sensitivity of the
      S/N gain to factors such as the shape of the input function, the time at which
      the conditions are switched and the magnitude of the activation. RESULTS: In
      human studies of activation sites in the visual cortex, primary motor and
      premotor areas, S/N improvements of 20%-30% were detected using the switched
      paradigms. Simulations show that this gain is virtually independent of activation
      magnitude and that there is a broad time window of 20 sec for making the switch
      between conditions. To obtain the highest S/N gain, a rapid bolus injection is
      required. CONCLUSION: Switched paradigms have the potential to significantly
      increase S/N in PET activation studies. In human studies, the S/N increase
      averaged 25% which is equivalent to increasing the number of counts collected by
      50%. Switched paradigms can be used to maximize the difference signal in many
      activation studies, and do not preclude the absolute quantitation of blood flow
      using the standard autoradiographic technique.

PMID- 7830137
TI  - Modeling analysis of platinum-195m for targeting individual blood-borne cells in
      adjuvant radioimmunotherapy.
AB  - The inability to eradicate a population of single, isolated, blood-borne tumor
      cells with the radionuclides currently in use may limit the efficacy of adjuvant
      radioimmunotherapy. We have examined the possibility of sterilizing single blood
      borne cells using surface-bound emitters of Auger and conversion electrons.
      METHODS: The number of cell-surface decays required for 99% sterilization was
      found by using the linear-quadratic model of cell survival (alpha = 0.3 Gy-1,
      alpha/beta = 10 Gy) to transform absorbed dose to survival probability. The
      absorbed dose to the center of the cell was calculated by evaluating the point
      dose kernel at the cell radius of 6 microns and multiplying it by the number of
      surface decays. A two-compartment model of whole-body pharmacokinetics was used
      to obtain the red marrow dose corresponding to a given number of cell-surface
      decays. RESULTS: Platinum-195m (T 1/2 = 4 days) proves to be a particularly
      effective radionuclide. The 195mPt protocol requires 1.2 GBq of injected activity
      and is calculated to give an average red-marrow dose of 1.23 Gy, well within
      marrow tolerance. CONCLUSION: Analysis of the targeting efficiency as a function
      of cell radius reveals that 195mPt is expected to sterilize cells with radii up
      to 8 microns without delivering more than 2.5 Gy to red marrow. It also emits
      photons that are appropriate for external imaging and has been used to study the
      biodistribution of cisplatin in humans. High-specific activity 195mPt may be
      obtained by decay of cyclotron-produced 195mIr (T 1/2 = 3.8 hr).

PMID- 7830138
TI  - Heterogeneity of myocardial perfusion provides the physiological basis of
      perfusable tissue index.
AB  - Assessment of viable from nonviable myocardium is critical for the care of
      patients being considered for revascularization procedures. Recently, the
      perfusable tissue index (PTI) has been proposed as an index of myocardial
      viability. METHODS: Computer simulations were performed for homogeneously and
      heterogeneously perfused tissue over a wide range of flows (0.04-6.4 ml/g/min)
      using both bolus and infusion inputs. RESULTS: PTI estimated from simulated
      homogeneously perfused tissue did reflect the amount of tissue being perfused
      independent of absolute level of flow, type of input or model configuration,
      whereas PTI obtained from simulated heterogeneously perfused tissue was
      consistently lower than the simulated "true" PTI and varied with flow, type of
      input function and model configuration. Flow estimated with 15O-water was not
      significantly different from that measured with radio labeled microspheres.
      CONCLUSION: Oxygen-15-water can diffuse into both acutely and chronically
      ischemic myocardium irrespective of its functional status. The results suggest
      that PTI is most likely an index of the heterogeneity of myocardial flow rather
      than an index of the amount of tissue being perfused. Its utility for delineating
      myocardial viability is thus related to the amount of tissue perfused that has
      low absolute levels of perfusion or high degrees of flow heterogeneity.

PMID- 7830139
TI  - Transmission computed tomography imaging of the head with a SPECT system and a
      collimated line source.
AB  - Transmission images of relatively high resolution as compared to SPECT are needed
      for brain SPECT quantification to provide skull thickness, attenuation
      coefficients and anatomical correlation. Consequently, a technique to acquire
      transmission CT images with a SPECT system by using a collimated line source
      positioned at the focal line of a fanbeam collimator (FBC) has been developed.
      METHODS: Computer simulations that model the transmission imaging system
      optimized the system resolution and tested the validity of a equation for the
      geometric efficiency of the line source collimator (LSC). Based on the computer
      simulations, a LSC was constructed with tantalum septa 100 mm long, 0.5 mm thick
      and spaced 1.0 mm apart. A 600-mm focal length FBC was used. Experiments were
      conducted to measure the system resolution and to determine the effect of the LSC
      on the amount of detected scatter. RESULTS: The simulations showed that without a
      LSC the transmission images have a longitudinal resolution (LR) characterized by
      the resolutions of the FBC (depth-dependent, approximately 8 mm FWHM at 150 mm)
      and the detector (approximately 4 mm). However, with an optimally designed LSC,
      the contribution of the FBC to the system resolution can be made negligible,
      creating a system with a LR that is comparable to the detector resolution and
      independent of object depth. Resolution experiments conducted with a lucite rod
      phantom showed that the LR and TR are better than 4.8 mm and confirmed the
      results of the computer simulations. CONCLUSION: Brain transmission images of
      relatively high isotropic resolution can be obtained using a SPECT system, a FBC
      and an optimized LSC.

PMID- 7830140
TI  - A Monte Carlo simulation model for radiation dose to metastatic skeletal tumor
      from rhenium-186(Sn)-HEDP.
AB  - A Monte Carlo model has been developed for simulation of dose delivery to
      skeletal metastases by the bone surface-seeking radiopharmaceutical 186Re (Sn)
      HEDP. METHODS: The model simulates: (1) the heterogeneous small scale geometry of
      the soft tissue/bone-spicule structure in the lesions as determined by
      histomorphometric measurements of histologic specimens, (2) the small scale
      spatial distribution of the radiopharmaceutical on the lesion bone spicule
      surface as determined by autoradiography, and (3) the 186Re beta and conversion
      electron decay spectrum and the associated charged particle transport within the
      modeled geometries. The results are compared with the commonly employed uniform
      lesion model, which assumes: (1) homogeneous lesion morphology, (2) uniform
      distribution of radioactivity within the lesion, and (3) complete energy
      deposition by charged particles within the lesion due to decay of this activity.
      Gamma and x-ray photons from the 186Re spectrum were assumed to escape from the
      lesion volume in both models. RESULTS: Results show a significant dependence on
      the bone volume fraction and hence on the histology of the lesion (lytic, blastic
      or mixed). The uniform lesion model calculations underestimate the radiation dose
      to blastic lesions by as much as a factor of 1.8. However, for lytic lesions with
      low bone volume fractions, both models provide similar dose values. CONCLUSIONS:
      These new model calculations provide a mechanism for optimizing treatment
      planning and dose response evaluations of therapeutic bone-seeking
      radiopharmaceuticals.

PMID- 7830141
TI  - Radionuclide studies of the upper gastrointestinal tract in children with feeding
      disorders.
AB  - The case of a female infant with a feeding disorder and with inadequate growth is
      described. In her workup, there was no evidence of an organic disorder. Barium
      studies of the upper GI tract showed normal anatomy and function. A radionuclide
      milk scan was helpful in demonstrating mild reflux and significantly delayed
      gastric emptying. There was a good response to therapy.

PMID- 7830142
TI  - 1994 task analysis of American certified nurse-midwifery.
AB  - The ACNM Certification Council is responsible to the American College of Nurse
      Midwives for the development, administration, and evaluation of a
      psychometrically sound and legally defensible certification examination in nurse
      midwifery. A task analysis study was conducted to investigate the knowledge,
      skills, and abilities that define American nurse-midwifery practice. A stratified
      sample of 825 American College of Nurse-Midwives members was asked to rate the
      frequency of performance and the criticality of 189 nurse-midwifery activities
      and 109 discrete diagnoses that the nurse-midwife might encounter while providing
      clinical care. The frequency and critically ratings were combined to generate an
      importance weight for each activity. Study data will be used as the basis of the
      examination blueprint in order to ensure job-related content validity. Aggregate
      data can also be used for curriculum development, self-assessment, and evaluation
      research purposes.

PMID- 7830143
TI  - Home-based services by nurse-midwives. Sample data from phase II of nurse
      midwifery care to vulnerable populations in the United States.
AB  - This article presents prospective data from Phase II of Nurse-Midwifery Care to
      Vulnerable Populations in the United States, about home-based health care,
      including home birth, provided to women and infants by CNMs and the type of
      practice in which these services are provided. Forty-one certified nurse-midwives
      collected data on 1,739 client visits, of which 234 occurred in the home. The
      results indicate that the majority of home visits occur within a practice setting
      that includes more traditional modes of service and that a proportion of women
      choose home as the place for health care.

PMID- 7830144
TI  - Postcoital contraception. Has its day come?
AB  - Although postcoital contraception might aid in reducing the occurrence of some
      unintended pregnancies, it is seldom used. This review summarizes the development
      of postcoital methods, focusing on the Yuzpe regimen, the most widely used
      emergency contraceptive in the United States. The article discusses its mechanism
      of action, safety, side effects, and effectiveness. Reasons for its limited use
      are discussed, as are recent findings that RU 486 may be a superior postcoital
      agent. Finally, a protocol for integrating the Yuzpe method into nurse-midwifery
      practice is presented.

PMID- 7830145
TI  - Use of pelvic tilt exercise for ligament pain relief.
AB  - The purpose of this study was to test the effectiveness of a pelvic (hip) tilt
      exercise in relieving ligament pain during pregnancy. A multiple pain measurement
      approach was used. The intensity of ligament pain was decreased as indicated by
      scores on three of four pain intensity measures. The duration of ligament pain
      also was reduced, although not significantly. Mean scores on all measures of
      ligament pain intensity, duration, and frequency were lower after the exercises
      were initiated. Verbal reports from subjects indicated that they had received
      effective pain relief from the exercise. Thus, pelvic (hip) tilt exercise appears
      to be effective in reducing ligament pain intensity and, to a lesser extent, pain
      duration. As a nurse-midwifery strategy, this exercise promotes patient/client
      comfort and facilitates self-care in the relief of ligament pain during
      pregnancy.

PMID- 7830146
TI  - Orientation of OB/GYN residents to ambulatory care. A nurse-midwifery approach.
AB  - Although certified nurse-midwives collaborate with ob/gyn residents in teaching
      settings, they are rarely given the opportunity to have input into how residents
      learn to deliver ambulatory care. This study is a preliminary evaluation of a
      program in which one nurse-midwife was assigned responsibility for the
      orientation and preceptorship of all post-graduate year 1 residents to the
      ambulatory care setting in an inner-city women's health center. At the end of the
      academic year, all of the post-graduate year 1s completed an evaluation of their
      orientation. Findings included positive responses to the preceptorship
      orientation and agreement that the residents were comfortable with the competence
      and educational background of the CNM preceptor. The recurring theme was that
      orientation by a CNM was an appropriate learning experience. Suggestions for
      improvement of the program are included.

PMID- 7830147
TI  - Primary care obstetrics and perinatal health in The Netherlands.
AB  - The Netherlands is the only industrialized country in which a large percentage of
      obstetric care takes place at home. Almost 31% of all deliveries are home
      confinements under supervision of a midwife or a general practitioner, and 84% of
      all postnatal care is given at home by maternity care assistants. To gain a
      better understanding of this unique situation, the structure of Dutch obstetric
      care is examined with special attention to the four pillars on which the system
      rests: the special protected position of the midwife, a generally accepted
      screening system for high-risk pregnancies, a well-organized maternity home care
      system, and the sociocultural environment in The Netherlands in which pregnancy
      and childbirth are considered normal physiological processes. Description of the
      obstetric system shows a degree of competition between the obstetricians,
      midwives, and general practitioners, in which the general practitioner has lost a
      considerable part of the "obstetric market."

PMID- 7830148
TI  - Management of anticipated and actual shoulder dystocia--interpreting the
      literature.

PMID- 7830149
TI  - Understanding diagnostic tests in the childbearing year.

PMID- 7830150
TI  - Sacrosanct concept of risk.

PMID- 7830151
TI  - Festschrift to Edward J. "Ted" Quilligan.

PMID- 7830152
TI  - Placenta pathology questions to the perinatologist.
AB  - There are many reasons to advocate a routine screening for placental lesions. A
      quick study of the surfaces of the freshly delivered organ gives much relevant
      information. In certain circumstances the organ should be studied histologically,
      so as to have a permanent record of the pathologic findings, and also to advance
      our knowledge of some features that we have as yet no answers to. This
      communication addresses three pathologic findings at placental examination:
      meconium staining, presence of nucleated red blood cells, and chorangiosis. In
      all of these lesions, additional data need to be collected with the help of
      perinatologists so that the pathologic features can be better understood. It is
      especially desirable that better time frames for the meconium injury and the
      secretion of nucleated red blood cells be known.

PMID- 7830153
TI  - Fetal cerebral metabolism: the influence of asphyxia and other factors.
AB  - Cerebral oxidative metabolism has been described in fetal sheep at two stages of
      development and is known to remain relatively constant over a wide range of
      oxygen levels in arterial blood. This constancy of oxygen consumption is caused
      by an increase in cerebral blood flow that matches the reduction in oxygen
      content and oxygen extraction. Although a number of factors are involved in the
      hypoxia-associated vasodilation (for example, oxygen, carbon dioxide, adenosine,
      prostaglandins, arginine vasopressin), its regulation is incompletely understood.
      During severe asphyxia, however, there is a limit to the vasodilator function,
      and both cerebral blood flow and oxygen consumption fall. The fetus can tolerate
      a certain degree of reduced oxygen uptake (possibly to 50% of control level) by
      various conservation techniques, but severe reductions are associated with
      neuronal damage. The primary substrate for the fetal brain under normal
      conditions is glucose, but the fetus can readily use anaerobic glycolysis and
      produce lactate under conditions of oxygen limitation. Lactate efflux from the
      brain is relatively slow, so prolonged and severe asphyxia may result in a high
      tissue level of lactate, which has been implicated in neuronal damage.

PMID- 7830154
TI  - The umbilical artery Doppler ultrasonographic gradient: confirmation, cause, and
      comparison of continuous-wave and duplex ultrasonographic pulsed-wave
      measurements.
AB  - The umbilical artery Doppler ultrasonographic gradient has been described, and
      the need for site-specific nomograms has been pointed out. However, controversy
      still exists about the cause of this phenomenon and the optimal site for
      obtaining umbilical artery Doppler ultrasonographic measurements. Cross-sectional
      measurements of umbilical artery flow velocity waveform (FVW) systolic/diastolic
      (S/D) ratios were therefore made in 35 gravid women during the second or third
      trimester of pregnancy with both duplex pulsed-wave (PW) and free-standing
      continuous-wave (CW) Doppler ultrasonographic equipment. Multiple duplex PW
      Doppler ultrasonographic signals were recorded at the abdominal cord insertion,
      placental cord insertion, and free cord sites. Multiple CW Doppler FVWs were
      obtained from four quadrants, in decreasing order of ease of measurement.
      Repeated-measures analysis of variance demonstrated a statistically significant
      decrease in mean and median values of the umbilical artery S/D ratio from the
      abdominal cord insertion site to the placental cord insertion site. The reduction
      in the value of the S/D ratio as the placental cord insertion site is approached
      results more from a decrease in the peak systolic maximum velocity envelope than
      from an increase in diastolic velocities. Moreover, mean and median CW Doppler
      ultrasonographic values correlate most closely with corresponding PW measurements
      of the free cord segment. These data confirm the presence of the umbilical artery
      Doppler ultrasonographic gradient. Decreasing values of the S/D ratio from the
      fetal abdomen to the placenta are a result of attenuation of the systolic maximum
      velocity envelope.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7830155
TI  - Electronic fetal monitoring and later outcome: a thirty-year overview.

PMID- 7830156
TI  - The ABCs of electronic fetal monitoring.
AB  - There have been too many surrogates used to define fetal asphyxia and too many
      surrogates used to time fetal injury. Low Apgar scores and the need for prolonged
      resuscitation, by themselves, are inadequate criteria for the diagnosis of
      perinatal asphyxia or subsequent neurologic handicap. Even with the addition of a
      low cord pH and seizures, it is not possible to infer neurologic handicap.
      Furthermore, acidosis and depression at birth (which should be referred to as
      "perinatal asphyxia") cannot measure the duration and extent of any prenatal
      asphyxial encounter. Nor can we use the absence of one or more of these signs to
      exclude perinatal asphyxia as the cause of injury. We cannot refer to fetal
      asphyxia and injury therefrom without defining our criteria and describing the
      model of asphyxia being invoked. Because ischemia to the brain and other organs
      (that is, localized asphyxia), not systemic global asphyxia, appears to be the
      major precursor of human fetal injury it seems unreasonable to insist on systemic
      fetal asphyxia at any time to validate the timing or mechanism of fetal injury.
      Most hypoxic newborn infants are not injured and most injured newborn infants are
      not hypoxic. Furthermore, that a baby is injured as a result of hypoxia during
      labor does not mean that the hypoxia was preventable. FHR patterns, properly
      interpreted, may be one of the most reliable determinants of subsequent
      neurologic outcome and depending on the circumstances may provide insight into
      the timing and mechanism of neurologic injury.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7830157
TI  - A multicenter evaluation of intramuscular ritodrine hydrochloride as initial
      parenteral therapy for preterm labor management.
AB  - Ninety-four patients in documented preterm labor received three intramuscular
      injections of ritodrine hydrochloride over an interval of 6 hours. They
      subsequently received the tocolytic agent intravenously for a minimum of 6 hours.
      The effects of ritodrine on uterine activity and the cardiovascular system were
      determined. Intramuscular ritodrine hydrochloride elicited a prompt and sustained
      reduction in the frequency of uterine contractions. The transition to intravenous
      treatment was achieved without an increase in uterine activity. Seventy percent
      of the patients had a sustained interval of uterine quiescence, and 96% had at
      least a 24-hour delay in delivery. Initial parenteral therapy with intramuscular
      ritodrine hydrochloride is safe and effective and may provide an alternative to
      intravenous therapy and a means of managing preterm labor during interhospital
      transport of a patient.

PMID- 7830158
TI  - Artifactually elevated basal uterine tonus resulting from measurement of
      hydrostatic pressure by transducer-tipped intrauterine catheters.
AB  - Accurate measurements of uterine activity are a valuable adjunct in the
      management of parturition. Recently transducer-tipped intrauterine pressure
      catheters (IUPC) have been advocated because of their accurate recording of
      uterine contraction pressures. We hypothesized that the transducer-tipped IUPC
      may record elevated basal uterine pressures because of measurement of additional
      hydrostatic pressures within the uterus. Eight laboring patients received
      intrauterine placement of a transducer-tipped IUPC. Catheters were zeroed to air
      pressure, electronic zero was checked, and monitors were calibrated before
      insertion. Catheters were not rezeroed during labor. Basal resting uterine
      pressures were recorded at insertion and before IUPC removal. After removal,
      electronic zero and catheter accuracy were tested in a specially designed
      pressure chamber (21 and 60 mm Hg). Electronic zero averaged -3 mm Hg before
      insertion and after removal. Baseline uterine resting tone averaged 15 +/- 1 mm
      Hg in seven patients, and one patient had a measurement of 34 mm Hg. Uterine
      resting tone remained stable in five patients and decreased to 20 mm Hg in the
      one patient with elevated basal tone. Uterine resting tone increased markedly to
      36 and 41 mm Hg in two patients with normal pressures on insertion, in spite of
      no evidence of uterine hyperstimulation. Extrauterine pressure testing recorded
      pressures of 23 +/- 1 and 62 +/- 1 mm Hg, respectively. Because of the
      measurement of the amniotic fluid column above the catheter, transducer-tipped
      IUPCs may artifactually elevate uterine pressure measurements and basal levels
      may shift during the course of labor.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7830159
TI  - Histologic observation of the ductus arteriosus in premature infants with
      intrauterine growth retardation.
AB  - The ductus arteriosus of 19 premature infants with intrauterine growth
      retardation (IUGR) (study group) was compared histologically with that of 22
      infants without IUGR (control group). The two groups exhibited no significant
      differences in gestational age, age at death, and frequency of disseminated
      intravascular coagulation. Maternal complications, that is, pregnancy-induced
      hypertension, cesarean section, and low umbilical artery oxygen tension values,
      were seen more frequently (p < 0.01) in the study group than in the control
      group. The histologic changes of ductus arteriosus, such as fragmentation,
      coagulation necrosis of the intimal elastic lamina, hemorrhage with necrosis, and
      loosening of elastic fibers and muscles in the tunica media, were seen more
      frequently in the study group. These findings are suggestive of both the
      maturation process and the prenatal hypoxic response of premature IUGR fetuses
      with chronic hypoxia. These changes may have produced subsequent patent ductus
      arteriosus, which in turn may have induced pulmonary hemorrhage.

PMID- 7830160
TI  - Electrogastrography in neonates.
AB  - We recorded the electrical signals from bipolar electrodes placed on the abdomen
      of 7 adults and 10 newborn infants. Data were analyzed by visual inspection and
      by a wave analysis computer program with a fast Fourier transform. Waves of 3
      cycles/min were recorded in adults, and similar 3 cycles/min waves were recorded
      in infants as well. The percentage of time of 3 cycles/min waves was lower in
      neonates (13.8% +/- 10.8%) than in adults (57.9% +/- 27.8%) (p < 0.01). Only an
      electrocardiogram superimposing the flat baseline was recorded in the remaining
      recording time. Spectral analysis confirmed the validity of the visual analysis,
      showing clear peaks at 0.05 Hz only when 3 cycles/min waves were visually present
      and motion artifact was absent. The electrode positions where percentage of time
      of 3 cycles/min waves was greatest were different for newborns and adults. There
      was no significant difference in the mean amplitude of the waves between groups.
      These facts indicate that the electrogastrogram of neonates is different from
      that of adults in terms of best electrode positions and percentage of time of 3
      cycles/min waves.

PMID- 7830161
TI  - A modified newborn intensive care unit environment may shorten hospital stay.
AB  - Premature infants with birth weights from 1121 to 2000 gm were assigned randomly
      to two groups. Experimental group infants were placed on a microprocessor
      controlled cradle that provided levels of motion and sound analogous to those of
      the third-trimester intrauterine environment. Periods of motion totaling 50% of
      the time were randomized on and off; motion speed was reduced 35% during a 12
      hour night period. A uterine souffle sound was generated continuously but varied
      in pulse rate and volume with the motion and speed of the bed. Experimental group
      infants (n = 20) were placed on the cradle under a radiant warmer as soon as
      their condition was stable clinically. Control group infants (n = 18) were
      usually placed initially under a radiant warmer and transferred to an incubator
      when their condition was stable. Otherwise, both groups received standard newborn
      intensive care unit care. The mean length of hospital stay was significantly
      shorter for experimental group infants than for control group infants after
      controlling for gestational age and weight on entry to the study. Experimental
      group infants began nippling earlier and stopped requiring gavage feedings
      sooner. Experimental group infants had a decreased incidence of apnea. Blinded
      Brazelton Neonatal Behavioral Assessment Scale scores for the Orientation and
      Range of State cluster scales were significantly better for experimental group
      infants. A retrospective contrast group of preterm infants who met study criteria
      had an average length of stay similar to that of the control group infants. These
      data support the hypothesis that appropriate levels and kinds of stimulation may
      facilitate the maturation of preterm infants.

PMID- 7830162
TI  - Special imaging casebook. Neonatal spermatic cord torsion and testicular
      infarction.

PMID- 7830163
TI  - Occupational medicine forum.

PMID- 7830164
TI  - Second-order selection bias.

PMID- 7830165
TI  - IARC Working Group on Carcinogenicity of Beryllium.

PMID- 7830166
TI  - A review of recent research on health effects of human occupational exposure to
      organic solvents. A critical review.
AB  - The health impact of workplace solvent exposure remains an issue of substantial
      interest and concern to occupational health professionals. As a result of
      research performed in the 1970s and 1980s, policies and programs were developed
      throughout the world to control excessive exposure to solvents. To an extent,
      these programs have been responsible for reduction of the occurrence of solvent
      associated encephalopathy and other health effects. In this review of research
      performed since 1985, particular attention is given to issues of reversibility of
      neurotoxicity following exposure cessation. Furthermore, health effects involving
      other organ systems, particularly reproductive, renal, and hepatic disorders, are
      discussed. Future research directions are discussed. Finally, the practical
      implications of these recent research findings are described with a focus on the
      management of prevention programs at the work site.

PMID- 7830167
TI  - Predicting risk of back injuries, work absenteeism, and chronic disability. The
      shortcomings of preplacement screening.
AB  - Preplacement screening is put forth by some as an effective method for preventing
      low back disability at the workplace. Although there are still large gaps in
      knowledge regarding the natural history of and risk factors for back disability,
      it is clear that the majority of costs are derived from the small proportion of
      those that will suffer with back symptoms for 6 months or more. Thus, if
      preplacement screening is to have an impact on health care spending and
      compensation costs, the screening test will have to be predictive not so much of
      all back injuries, but rather of work absenteeism and especially chronic
      disability. This paper presents some criteria for evaluating a screening program
      and explores the effect of choosing different outcomes for evaluation. The
      literature on the effectiveness of a number of preplacement screening techniques
      is examined. Current legislation related to preplacement screening is also
      described. The natural history, etiologic factors, and prognostic markers for
      back injuries need to be elucidated further before effective screening strategies
      can be developed to reduce the incidence of back injuries and back disability in
      the population.

PMID- 7830168
TI  - Assessment of a screening protocol for occupational renal disease.
AB  - Using 10 guidelines for medical screening programs, this review assesses a
      screening protocol that seeks to identify presymptomatic occupational renal
      disease among workers with nephrotoxin exposure. The protocol uses urinary
      markers of early renal dysfunction for the screening test. The review reveals
      that arguments for screening are the clinical significance of renal disease,
      worker acceptance of urine collection, the availability of exposure reduction as
      an intervention, and the availability of diagnostic and treatment facilities.
      Obstacles to screening are the lack of an effective intervention, the lack of
      strong evidence to indicate that an elevation in the urinary markers represents a
      preclinical stage of occupational renal disease, and the absence of firm numbers
      to demarcate normal from elevated concentrations of urinary markers. Given these
      obstacles, screening for occupational renal disease is not recommended.

PMID- 7830169
TI  - Backache and work incapacity in Japan.
AB  - No one is spared a regional backache. Some episodes will compromise function to
      the extent of work incapacity. Throughout the industrialized world, workers'
      compensation insurance programs provide recourse for the segment of people whose
      incapacitating backache is held to have arisen out of and in the course of
      employment. Most programs have evolved from the Prussian paradigm introduced a
      century ago. That evolution represents country specific, de facto experiments in
      health policy. In the case of Japan, the Prussian paradigm was imposed on a very
      distinctive tradition at the end of World War II. Therein lies one of the more
      dramatic experiments of health policy. This essay attempts to document the
      process that resulted. To gain such insight, relevant physicians and bureaucrats
      in Japan were interviewed and government documents reviewed. This information was
      supplemented by nonsystematic culling of relevant reflections of scholars also
      pursuing the heuristic method but with different, usually nonclinical, tempering.
      It is clear that Japan has evolved an approach to the worker with an
      incapacitating backache that favors options other than recourse in workers'
      compensation for redress.

PMID- 7830170
TI  - Epidemiologic features of urolithiasis among industrial employees. The Israeli
      CORDIS Study.
AB  - We examined the prevalence of urolithiasis in 5574 men and women employees in 21
      industrial plants in Israel who were screened for cardiovascular risk factors
      between 1985 and 1987 (the CORDIS Study). Among the data gathered were previous
      physician diagnosis of urolithiasis and ergonomic and demographic data.
      Urolithiasis was much more frequent in men than in women (age-adjusted prevalence
      of 4.5% in men and 1.2% in women, P < .0001). Older subjects had higher
      prevalence than young subjects. There were ethnic differences, and the highest
      prevalence was in subjects of European origin. Of the occupational factors, only
      industrial sector was related to prevalence of urolithiasis. Urolithiasis was
      more frequent among employees in wood industries than in other sectors (P < .05).
      We concluded that there is an effect of industrial sector on the prevalence of
      urolithiasis. To determine the cause and magnitude of the association of wood
      industries with increased prevalence of urolithiasis, ergonomic and chemical
      factors should be investigated.

PMID- 7830171
TI  - Risk factors for injury during basic military training. Is there a social element
      to injury pathogenesis?
AB  - A retrospective case-control study into the risk factors for injury during basic
      military training was conducted at the Recruit Training Unit, Royal Australian
      Air Force Base Edinburgh, South Australia. Case subjects were recruits suffering
      a musculoskeletal injury during the course, severe enough to result in
      backcoursing (being delayed and joining a later course) and usually requiring the
      loss of 5 days of training. Control subjects were 629 recruits selected randomly
      from recruits who were not case subjects from the same period of Jan 1, 1985 to
      Dec 31, 1990. Two hundred thirty-eight cases were identified (2.7% of the recruit
      population), of which 123 were overuse-type injuries and 115 acute-type injuries.
      Most injuries occurred in the first 2 weeks of training. Bivariate and logistic
      regression analysis of possible risk factors for injury was conducted, both for
      all case subjects and for the subgroup of case subjects with overuse injuries.
      Statistically significant associations were identified for female gender, body
      mass index > 26.9, winter training, a history of lower limb injury, and the
      presence of a lower limb deformity. All these associations were stronger for
      overuse injury, and preenlistment physical activity was also significantly
      associated with overuse injury. No significant association was found for height,
      weight, age, smoking, or gender makeup of courses. Most striking was a large rise
      in overuse injury incidence in women over the period of study, from 0.2% in 1985
      to 8.8% in 1990. Reasons for this increase may include "social pathogenesis."

PMID- 7830172
TI  - Relationship between physical activity and risk factors for cardiovascular
      disease among law enforcement officers.
AB  - This investigation examined the associations between exercise habits, measures of
      physical fitness, and 10-year cardiovascular disease risk (CVD10, expressed as %)
      among 470 law enforcement officers of differing ages (range = 21 to 63 y). Only
      32% of this group exercised regularly (> or = 3 days/week, > or = 20 min/session,
      > or = preceding 4 weeks). Only exercising subjects > 48 years old exhibited a
      significantly (P < .01) lower 10-year risk of a CVD event than their inactive
      peers (12.2 +/- 5.6 vs 16.3 +/- 6.9%, mean +/- SD). At all ages, the peak oxygen
      consumption per unit time was higher (50.1 +/- 6.7 vs 44.8 +/- 6.1 mL.kg-1.min-1)
      in the exercising than in the nonexercising group. Exercising subjects < or = 36
      years old were significantly (P < .05) leaner than nonexercisers (16.3 +/- 5.5 vs
      19.6 +/- 5.5% body fat, respectively) and had greater muscular endurance (45 +/-
      9 vs 40 +/- 9 60-s sit-ups, respectively). These data suggest that exercise
      reduces CVD risk by modifying major CVD risk factors only in law enforcement
      officers > 48 years old.

PMID- 7830173
TI  - Asthma experience in an occupational and environmental medicine clinic. Low-dose
      reactive airways dysfunction syndrome.
AB  - The etiology of adult-onset asthma is incompletely understood. High-intensity
      exposure to irritants is one accepted risk factor and such cases are termed
      Reactive Airways Dysfunction Syndrome. The contribution to asthma of less intense
      and less acute exposure to irritants remains to be clarified. We report on 10
      cases of nonsensitization adult-onset asthma in settings of exposure to
      noticeable but distinctly "tolerable" levels of inhalation irritants. This series
      of 10 cases represent 31% of verified asthma cases seen in our environmental and
      occupational medicine referral clinic over a 5-year period. We believe further
      exploration of this phenomenon of low dose Reactive Airways Dysfunction Syndrome
      is warranted.

PMID- 7830174
TI  - Reading the handwriting on the wall.

PMID- 7830175
TI  - Custom CAD/CAM total temporomandibular joint reconstruction system: preliminary
      multicenter report.
AB  - PURPOSE: The purpose was to test the outcome of a custom computer assisted
      design/computer assisted manufactured (CAD/CAM) total temporomandibular joint
      (TMJ) reconstruction system. PATIENTS AND METHODS: There were 215 patients (13
      males and 202 females); the average age at reconstruction was 40.9 +/- 10.3 years
      (range, 15 to 77 years). There were 363 joints placed, 296 bilateral and 67
      unilateral. The patients had TMJ problems for an average of 10.3 +/- 7.0 years
      (range, 1 to 44 years), and had undergone a mean of 5.4 +/- 4.8 (range, 0 to 28)
      prior unsuccessful surgeries. Preoperative and postoperative data were collected
      for up to 48 months using a standardized data collection format. Subjective data
      related to pain, function of the lower jaw, and diet, were obtained using a
      visual analogue scale. Objective measures of mandibular range of motion were made
      directly on the patient preoperatively and postoperatively. RESULTS: Preliminary
      analysis of these data reveals a statistically significant decrease in pain, an
      increase in function, and improvement in diet (P < .0001) from the preoperative
      measurements to 1 and 2 years postoperatively. There was also improvement in
      mandibular vertical range of motion. The number of previous surgeries was a
      strong predictor of postoperative pain, function, and diet scores, as well as of
      maximal interincisal opening. A life table analysis of failures indicates good
      durability of the prosthesis over time. CONCLUSION: These preliminary data
      indicate that this custom CAD/CAM total TMJ reconstruction system seems to be
      useful in the treatment of the multiply operated, and/or anatomically mutilated
      TMJ.

PMID- 7830176
TI  - Alteration of temporomandibular joint symptoms after orthognathic surgery:
      comparison with healthy volunteers.
AB  - PURPOSE: The purpose was to investigate alterations in temporomandibular joint
      (TMJ) dysfunction after orthognathic surgery. PATIENTS AND METHODS: TMJ symptoms
      of preoperative patients (n = 30) were compared with those of healthy volunteers
      (n = 30), and changes in the symptoms were evaluated at 3- and 6-month
      postoperative intervals. RESULTS: There was no significant difference in the
      incidence of TMJ sounds, deviation of mouth opening, and tenderness of TMJ and
      masticatory muscles between patients and volunteers. Patients did not report TMJ
      symptoms significantly more often than the control subjects. At both 3 and 6
      months after surgery, half or more of the patients showed no change in TMJ
      sounds, deviation of mouth opening, or tenderness of TMJ and masticatory muscles.
      At each evaluation, some patients exhibited improvement of TMJ symptoms or showed
      changes for the worse. Findings of TMJ sounds were observed to be associated with
      the postoperative reduction of mandibular mobility. CONCLUSION: These results
      suggest that alterations of TMJ symptoms after orthognathic surgery do not always
      result from the correction of malocclusion.

PMID- 7830177
TI  - Propofol infusion technique for outpatient general anesthesia.
AB  - PURPOSE: The purpose was to evaluate the suitability of a continuous propofol
      infusion in combination with alfentanil for outpatient general anesthesia in an
      oral and maxillofacial surgery practice. MATERIALS AND METHODS: Twenty-seven ASA
      1 patients were selected to undergo oral and maxillofacial surgery outpatient
      procedures of short duration. Induction of anesthesia was accomplished with 1
      mg/kg intravenous (i.v.) propofol and 10 micrograms/kg i.v. alfentanil. Local
      anesthesia was administered. General anesthesia was maintained with a continuous
      infusion of 150 micrograms/kg/min of propofol. Various physical and psychomotor
      responses were recorded during induction, maintenance, emergence, and recovery.
      RESULTS: Anesthesia was successfully induced in all patients with single, slowly
      titrated, bolus doses of 1 mg/kg of propofol and 10 micrograms/kg of alfentanil.
      Induction of general anesthesia occurred in less than 1 minute in all cases and
      no excitatory phenomena, tremor, or hypertonus were observed. Maintenance of
      anesthesia was adequately accomplished and cardiovascular parameters remained
      within acceptable limits throughout the procedure. The average length of surgery
      was 22 minutes. Movement to surgical stimulus was minimal and easily managed with
      additional local anesthetic and/or a 10-mg bolus of propofol. Time to eye opening
      was approximately 5 minutes from the discontinuation of the propofol infusion. No
      emergence phenomena were observed. All patients were ready for discharge with
      baseline psychomotor activity within 30 minutes following the end of the
      procedure. The average total dose of propofol was 350 mg and the average dose of
      alfentanil was 750 micrograms. CONCLUSION: This anesthetic technique has numerous
      advantages with minimal side effects, and should be considered for routine use
      for outpatient general anesthesia in oral and maxillofacial surgery.

PMID- 7830178
TI  - Surgical treatment of proptosis bulbi by three-wall orbital decompression.
AB  - PURPOSE: Three-wall orbital decompression was tested using a coronal approach as
      a technique. PATIENTS AND METHODS: Three-wall orbital decompression by a coronal
      approach was performed in three patients with proptosis due to Grave's
      ophthalmopathy, in six patients with Grave's ophthalmopathy because their vision
      was threatened due to optic nerve compression, and in one patient with exorbitism
      due to Crouzon's syndrome for cosmetic rehabilitation. RESULTS: Proptosis
      reduction averaged 4.7 mm. The technique provides good access to the orbital
      walls, facilitating adequate proptosis reduction, and leaves no visible scar.
      Diplopia, present preoperatively in four patients, was improved in three patients
      and unchanged in one. There was no loss of visual acuity.

PMID- 7830179
TI  - Mucosal condition of the oral cavity and sites of origin of squamous cell
      carcinoma.
AB  - PURPOSE: This study investigated the clinical appearance of the affected mucosa
      in patients with squamous cell carcinoma (SCC) in the oral and oropharyngeal
      region. PATIENTS AND METHODS: The mucosal conditions of 396 patients was
      classified into two types. Type A, showing ulcer formation and/or tumor
      formation, and type B, showing only mucosal enlargement without any other
      abnormality. RESULTS: Type A was detected in the oral cavity and oropharynx, and
      type B was observed only in the upper and lower alveolus and gingiva. Of 14 type
      B patients histologically evaluated for the relationship between the tumor cells
      and surface oral epithelium, 10 showed a disconnection between the epithelium and
      the tumor cells, whereas in two the tumor cells extended into the epithelium.
      CONCLUSION: It was concluded that SCC of type B is not of oral epithelial origin,
      but is of maxillary sinus epithelium or odontogenic cell origin. In the mandible,
      type B SCC originates from odontogenic epithelium (odontogenic carcinoma).

PMID- 7830180
TI  - Columella lengthening using a cartilage graft in the bilateral cleft lip
      associated nose: choice of cartilage according to age.
AB  - PURPOSE: This article describes the technique of columellar lengthening using a
      cartilaginous strut in patients with a severely deformed bilateral cleft lip
      associated nose. MATERIALS AND METHODS: When the upper lip is not deficient, and
      especially when resection of lip scar tissue is indicated, the Millard forked
      flap technique is recommended. Advancement of the prolabium into the columella
      for lengthening, combined with an Abbe flap for upper lip reconstruction, is
      indicated when a deficient upper lip is unable to provide adequate donor tissue.
      A cartilaginous strut is inserted behind the forked flap or the advanced
      prolabium. According to the age of the patient, septal cartilage, costal
      cartilage, or ear cartilage is selected. Ten patients with a severely deformed
      bilateral cleft lip-associated nose underwent these procedures. RESULTS: In each
      case, the columella was lengthened satisfactorily. In four patients, the scar
      became hypertrophic at the base of the columella and scar revision was performed
      secondarily. CONCLUSIONS: A cartilaginous strut is the key to avoiding the
      tendency toward retraction or thickening of the lengthened columella. It gives a
      slight lift to the tip, provides more definition, and improves the columellar
      contour.

PMID- 7830181
TI  - A new three-dimensional treatment algorithm for complex surfaces: applications in
      surgery.
AB  - PURPOSE: Recent advances in computer technology enable automatic reconstruction
      of surface models using digitized contour lines and three-dimensional (3D)
      representation on a graphic terminal. This work was aimed at obtaining 3D
      reconstructions of facial bones to help guide oral surgery and complex dental
      implantology procedures. MATERIAL AND METHODS: The starting point was a computed
      tomographic examination. The limits of the cortical bone were automatically
      outlined and then digitized using a special computer program. The resulting data
      were then compiled for computer-aided design (CAD) purposes, and a virtual 3D
      model of the bone was mathematically computed. This model was next transferred to
      a computer program that piloted a CAD/computer-aided manufacture (CAM) machine
      that guided a laser stereolithography process. RESULTS: The early results of the
      use of 3D images, as well as solid models, for clinical and surgical purposes,
      indicate a high degree of reliability in morphologic diagnosis, determining the
      surgical procedure, and establishing the subsequent prognosis.

PMID- 7830182
TI  - The effect of polytetrafluoroethylene cylinders on osteogenesis in rat fibular
      defects: a preliminary study.
AB  - PURPOSE: This study was designed to evaluate the use of a hollow
      polytetrafluorethylene stent on the healing of continuity defects in the rat
      fibula. MATERIALS AND METHODS: Twenty-one animals were divided into four groups.
      Group 1 (n = 10) had an 8-mm segment of bone and periosteum removed with no
      interpositional stent. Group 2 (n = 10) had bone removed, but the periosteum was
      maintained and no stent was placed. Group 3 (n = 11) had bone and periosteum
      removed and placement of a stent. Group 4 (n = 10) had only bone removed and
      placement of a stent. The animals were sacrificed after 12 weeks and the defects
      were evaluated clinically and radiographically. RESULTS: Radiographic analysis
      showed that nine of 10 fracture gaps in group 1 failed to heal. In group 2, seven
      of 10 gaps did not heal; three showed partial calcification. In group 3, four of
      11 gaps were nonhealed, five showed partial calcification, and two showed
      complete calcification. In group 4, only two of 10 gaps failed to heal, seven
      showed partial calcification, and one was completely calcified. Clinical
      evaluation showed a similar trend. CONCLUSION: These findings suggest that guided
      tissue regeneration could potentially be used to bridge continuity defects
      without the need for a graft.

PMID- 7830183
TI  - Temporal dynamics of healing in rabbit cranial defects using guided bone
      regeneration.
AB  - PURPOSE: The objective of this study was to histologically evaluate the early
      stages of bone regeneration using rabbit calvaria defects in conjunction with
      guided tissue regeneration. MATERIALS: A semilunar cutaneous-periosteal flap was
      raised on the forehead of four rabbits exposing the top of the skull. A
      standardized transosseous skull defect (> or = 15 mm in diameter) was made in the
      area of the right parietal bone with a rotating round bur. Care was taken not to
      damage the underlying dura. A flat expanded polytetrafluoroethylene (ePTFE)
      membrane was placed to cover the defect. The membrane was tightly adapted,
      extending at least 4 mm onto intact bone, and the flap was sutured. One, 2, 3,
      and 5 weeks later, the specimens were removed and processed using standard,
      undecalcified, hard-tissue histologic techniques. Contact radiographs were also
      taken. RESULTS: Bone growth increased with time, starting at the borders of the
      defect. At 1 week, trabeculae of woven bone grew into the highly vascularized
      loose connective tissue occupying the defect. Two weeks postsurgery, isolated
      islands of new bone were detected in this connective tissue. Subsequently,
      neighboring small islands merged to form large islands. In later stages, the
      primary trabeculae of woven bone were reinforced by layers of regularly deposited
      lamellar bone. CONCLUSION: Rabbit calvaria defects treated by guided tissue
      regeneration heal by ingrowth of woven bone from the defect margins and by
      formation of bony islands within the defect area. Bone healing showed the
      histophysiological characteristics of intramembranous bone.

PMID- 7830184
TI  - Management of the diabetic oral and maxillofacial surgery patient.

PMID- 7830185
TI  - Steroid-induced psychosis: report of case.

PMID- 7830186
TI  - Treatment of craniofacial metastasis of a renal adenocarcinoma: report of case
      and review of literature.

PMID- 7830187
TI  - An extraskeletal chondrosarcoma of the maxilla: a case report.

PMID- 7830188
TI  - Topical tetracycline-induced neuritis: a case report.

PMID- 7830189
TI  - Malignant melanoma masquerading as myofibrosarcoma: an immunohistochemical and
      electron microscopic analysis.

PMID- 7830190
TI  - Cervical cellulitis and mediastinitis caused by odontogenic infections: report of
      two cases and review of literature.

PMID- 7830191
TI  - Embolization of arteriovenous fistulae of the maxillary artery after Le Fort I
      osteotomy: a report of two cases.

PMID- 7830192
TI  - Acute pulmonary edema developing after laryngospasm: report of a case.

PMID- 7830193
TI  - Rhinocerebral mucormycosis with severe oral lesions: a case report.

PMID- 7830194
TI  - A microplate and screw technique for intraoral open reduction of mandibular angle
      fractures.

PMID- 7830195
TI  - Modified technique for adapting a mandibular angle superior border plate.

PMID- 7830196
TI  - Switching endotracheal tubes.

PMID- 7830197
TI  - Nocturnal bruxing events: a report of normative data and cardiovascular response.
AB  - Twenty subjects referred to a sleep laboratory for evaluation of sleep apnoea and
      found not to have any sleep disordered breathing problems were evaluated in this
      study. Bruxing events were recorded for frequency, duration, association with
      sleep stage and sleep position. The possible association between leg movements
      and bruxing events was also evaluated, but did not reveal any common mechanism.
      This study revealed that heart rate during bruxing events increased on average by
      16.6%.

PMID- 7830198
TI  - Some clinical investigations on retention forces of maxillary complete dentures
      with the use of denture fixatives.
AB  - The aim of this study was to evaluate objectively and clinically the relative
      improvement in retention forces of complete dentures with the use of three
      proprietary denture fixatives. Using the UCL Retentiometer, retention forces of
      ill-fitting maxillary complete dentures were measured with saliva alone as the
      interface medium and with the use of the three test denture fixatives in
      edentulous subjects over a period of 6 h. Results showed that forces with saliva
      alone were consistently and significantly lower when compared with the forces
      measured at any test period with the use of the test fixatives. A sixfold
      improvement in forces from the salivary baseline values was observed when these
      materials were used. However, the test fixatives showed substantial variations in
      retention forces depending on the physical formulation of the material. Whilst
      the powder variety was effective immediately after its application, retention
      forces with the liquid and paste materials did not peak until 3 h post-insertion.
      Measurements at 6 h post-insertion stage showed that the powder fixative was the
      least effective of the three materials. This was mainly attributed to the rapid
      washing of the active ingredients by saliva because of the absence of oily base
      present in the paste and liquid materials.

PMID- 7830199
TI  - Effect of microwave irradiation on the flexural strength and residual monomer
      levels of an acrylic resin repair material.
AB  - The degree of polymerization of an acrylic resin repair material, as established
      by residual monomer estimation, was compared using three different polymerization
      methods, i.e. bench-cure, hydroflask-cure and microwave irradiation cure. The
      repair strength of a conventional heat-polymerized resin was then assessed
      following repairs using each of these three methods. The lowest level of residual
      monomer was achieved with the microwave irradiation cure. It was also
      demonstrated that of the three methods, polymerization using microwave energy
      resulted in the strongest repair.

PMID- 7830200
TI  - Repair of glass ionomer cements--methods for conditioning the surface of the
      cement to achieve bonding.
AB  - Two chemically different glass ionomer cements (Ketac Fil and ChemFil II Caps)
      and three different methods of conditioning the surface for repair were
      evaluated. Specimens of each material were prepared, aged and sectioned. The cut
      surfaces were treated with either phosphoric acid, polyacrylic acid or a
      combination of phosphoric acid followed by polyacrylic acid. Freshly mixed glass
      ionomer cement was injected against the treated surface and allowed to set under
      simulated intra-oral conditions. The specimens were then tested to failure in
      flexion after 7 days storage. The flexural strength of the repaired specimens was
      compared with that of control specimens of the same materials. The flexural
      strength of the repaired specimens was less than that of the controls. Treatment
      of the fractured surface with polyacrylic acid produced the weakest repair, and
      the use of phosphoric acid as the conditioning agent produced repaired specimens
      approximately 80% of the strength of the controls.

PMID- 7830201
TI  - Assessment of treatment outcome in patients with craniomandibular dysfunction.
AB  - Psychosocial, socio-demographic and symptom characteristics have been shown to be
      associated with treatment outcome in patients with craniomandibular dysfunction
      (CMD). This study was performed to assess to what extent symptoms and correlates
      of CMD change as a consequence of conservative treatment for CMD. Treatment
      outcome in a group of CMD patients treated with a stabilization splint
      (experimental group) was compared with that of a group of patients with CMD who
      were not treated for CMD (control group). Patients in the experimental group had
      fewer symptoms of CMD at the end of treatment. However, several symptoms and
      correlates of CMD also improved in the control group (severity of pain, joint
      noises, ear symptoms). It was therefore questioned whether all improvements in
      symptoms and correlates of CMD in the experimental group could be attributed to
      the treatment received. Results suggest that the main improvement that might be
      ascribed to therapy was a decrease in 'jaw symptoms'. There was a noticeable
      decrease in depression and an increased use of 'planned actions and rational
      thinking' as a coping style in the experimental group whereas these variables did
      not change in the control group. Implications and suggestions for further
      research are discussed.

PMID- 7830202
TI  - Craniomandibular dysfunction: patient characteristics related to treatment
      outcome.
AB  - In a previous study it was concluded that only a few changes in symptoms related
      to craniomandibular dysfunction (CMD) could be attributed to therapy. It was
      suggested that psychosocial and socio-demographic variables, as well as symptom
      characteristics, could be responsible for the unconvincing treatment outcome in
      patients treated with a splint. The present study was performed to investigate
      whether socio-demographic characteristics, symptom characteristics and various
      psychosocial variables are associated with treatment outcome in patients with CMD
      treated with a splint. Treatment outcome was determined by using self-reported
      follow-up data. Results showed that patients with a negative treatment outcome
      were older, reported more and more severe symptoms and correlates of CMD,
      reported fewer stressors and more frequently considered health to be determined
      by external factors than patients who were treated successfully. The two groups
      could not be differentiated with regard to anxiety and depression. Results are
      interpreted with regard to the prediction of treatment outcome.

PMID- 7830203
TI  - Adaptation to the cavity floor of the light-cured glass ionomer cement base under
      a composite restoration.
AB  - The study attempted to assess methods of prevention of the formation of a
      contraction gap in a cylindrical enamel and dentine cavity. The influence has
      been investigated of the tensile bond strength of cement/dentine and
      cement/composite resin and the direct tensile strength during setting of light
      cured glass-ionomer cements. The interface between composite resin/cement and
      cement/dentine were viewed and photographed by replica techniques under an SEM
      (Scanning Electron Microscope). The most noticeable finding was that an enamel
      and dentine cavity applicated with light- and auto-cured glass-ionomer cement
      generally presented with a small construction gap at the tooth restoration
      interface. However, the light-cured glass-ionomer base (Vitrabond) exhibited
      significantly better tensile bond strength to dentine and resin performance than
      the conventional glass-ionomer tested. This study revealed that there was no
      clear relationship between the adhesion to dentine and the adaptation to the
      dentine cavity floor.

PMID- 7830204
TI  - The prevalence of cardinal TMJ dysfunction symptoms and its relationship to
      occlusal factors in Japanese female adolescents.
AB  - Cross-sectional data were obtained from 1182 Japanese high school girls of 12 and
      15 years old. The data were analysed for the prevalence of specific occlusal
      features and the prevalence of cardinal Temporomandibular Joint Dysfunction
      (TMJD) symptoms in different occlusion groups. The associations between occlusal
      features and TMJD symptoms were analysed by the Z-analysis. The results were as
      follows: the prevalence of TMJD symptoms (total) was about 23% in both age groups
      examined. Noise had the highest prevalence of the specific TMJD symptoms in both
      age groups (16% and 11%). With age and for different occlusion groups, there was
      a significant increase in deviation on opening (P < 0.001) and a decrease in pain
      and noise (P < 0.05). No significant associations were found between the
      occurrence of TMJD symptoms (total) and occlusal features in all the examined
      occlusion groups. With respect to specific TMJD symptoms, however, the
      investigation of the different groups revealed a significant association (P <
      0.05) of intra-arch occlusal (crowding) features with the occurrence of deviation
      on opening and with the occurrence of the combined TMJD symptoms which include
      deviation on opening. This indicates that crowding may be an important sign for
      predisposing TMJD. For the other single disorder symptoms (except pain), we did
      not find a significant relationship (P < 0.05) with aspects of occlusion, which
      may confirm a multifactorial TMJD problem wherein occlusal features can have a
      contribution to TMJD.

PMID- 7830205
TI  - Heats of reactions between dentine bonding agents and tooth components.
AB  - The heat of reaction of dentine bonding agents alone and dentine bonding agents
      with dentine, hydroxyapatite and collagen were measured using a differential
      scanning calorimeter (DSC) in the isothermal mode. The bonding agents were
      Scotchbond and Panavia Ex adhesives, and GC Fuji-II glass ionomer cement. The
      heat of reaction for Scotchbond and Panavia Ex bonding adhesives were 44.3 and
      6.9 mcal/mg, respectively. Furthermore, results support the view that the glass
      ionomer cements adhere to tooth structure by chemical bonding.

PMID- 7830206
TI  - Condylar asymmetry and its relation to age in a group of patients with a
      craniomandibular disorder of myogenous origin.
AB  - A group of patients with a myogenous origin of craniomandibular disorders was
      found to show a variation of condylar asymmetry with age. The curve obtained by
      plotting patient age against their asymmetry index was parabolic in nature. This
      differed from a group of patients with an arthrogenous origin of pain, where a
      linear correlation with age, with a negative slope, had previously been found.
      The mean asymmetry index for this group of patients was found to be 23.77%. This
      is higher than that reported for a group of patients with a craniomandibular
      disorder of arthrogenous origin, namely 18.76%. It appears that these two groups
      differ in the variation of condylar asymmetry with age..

PMID- 7830207
TI  - Some principles in the dental crown construction in permanent maxillary centrals
      of Slovenians.
AB  - To increase the understanding of the incisors crown form, the lingual fossa
      depth, crown width and crown thickness between lingual marginal ridges of the
      permanent maxillary centrals were measured on 257 stone casts of Slovene
      children. The right-left, male-female differences, as well as the correlations
      between the variables themselves were analysed. Male centrals exhibited wider and
      thicker crown compared to female centrals, while the lingual fossa depth showed
      no sex differences. A positive correlation in terms of positive allometry between
      lingual fossa depth and crown width was established. A negative lingual fossa
      depth-crown thickness correlation was found with female left centrals. High right
      left symmetry was established, except for the directional asymmetry of all three
      measured variables on female centrals. The results indicate that the positive
      correlation in terms of positive allometry between the thickness of the lingual
      marginal ridges and the crown width is one of the basic principles of the crown
      formation for the permanent maxillary centrals. Usually we have to work with
      absolute thickening of the lingual marginal ridges because relative thickening on
      the account of the crown thickness is less usual. The latter possibility is less
      favourable for the firmness of the dental crown.

PMID- 7830208
TI  - Fatal sequel to dental implant surgery.
AB  - The rare complication of fatal venous air embolism arising as a direct result of
      dental implant surgery in the mandible is depicted. The deaths arose from the
      erroneous use of an air/water coolant mixture with internally irrigated implant
      drills. The pathogenesis and consequence of air embolism is discussed.
      Practitioners are warned about the dangers of using air-driven equipment during
      implant surgery.

PMID- 7830209
TI  - A simple test for determination of the preferred chewing side.

PMID- 7830210
TI  - The source of messages produced during facilitated communication with a boy with
      autism and severe mental retardation: a case study.
AB  - Assessed the source of messages produced through facilitated communication with a
      youth with autism and severe mental retardation using message-passing and picture
      naming procedures. Results indicated that the facilitator was the source of the
      communications produced during the assessment; correct responding occurred only
      when the facilitator had knowledge of the correct answer. These findings are
      consistent with the results of other research demonstrating cuing, influence, or
      control of facilitated communications by the individuals providing assistance
      (facilitators). Implications for ethical practices by professionals in the
      context of facilitated communications are briefly discussed.

PMID- 7830211
TI  - Maternal child-rearing behavior in three groups: cystic fibrosis, insulin
      dependent diabetes mellitus, and healthy children.
AB  - Compared child-rearing behaviors among mothers of children (ages 4-14) with
      cystic fibrosis (CF) (N = 26), insulin-dependent diabetes mellitus (IDDM) (N =
      26), and mothers of physically healthy children (N = 26), on six domains,
      including involvement, limit setting, responsiveness, reasoning and guidance,
      free expression, and intimacy using the Iowa Parent Behavior Inventory. Maternal
      Reports of their child-rearing behavior were comparable across the three groups
      with one exception: Mothers of children with chronic illnesses (CF and IDDM) were
      significantly less likely to set limits than mothers of healthy children. The
      present findings are consistent with those of other studies that have identified
      few differences in child-rearing practices between mothers of children with
      chronic illnesses and mothers of healthy children. Future research should
      identify situation-specific parenting tasks unique to childhood chronic illness.

PMID- 7830212
TI  - Parenting style and developmental status among children with nonorganic failure
      to thrive.
AB  - Examined differences in several developmental indices of competence among 102 low
      income, inner-city, predominantly African American children with non-organic
      failure to thrive (NOFTT) and a comparison group of 67 children with adequate
      growth matched on age, gender, race, and socioeconomic status. Parents were
      categorized into one of three groups (nurturant, authoritarian, and neglecting)
      based on observations during feeding. Parents of children with NOFTT were less
      nurturant and more neglecting than parents of comparison children. Associations
      between parenting style and children's social-cognitive development were similar
      across groups. Children of nurturant parents consistently demonstrated better
      social-cognitive development. Results support the importance of considering
      heterogeneity among high-risk families and the need to examine the relationships
      linking parenting style and child development.

PMID- 7830213
TI  - Children awaiting invasive medical procedures: do children and their mothers
      agree on child's level of anxiety?
AB  - Examined correspondence between mother and child reports of child anxiety
      immediately preceding a scheduled invasive medical procedure. The State-Trait
      Anxiety Inventory for Children (STAIC) was administered to 101 children ages 10
      18 years. Mothers completed the STAIC and the State-Trait Anxiety Inventory to
      assess their perceptions of the child's anxiety and their own level of anxiety,
      respectively. Children were reported to have significantly more state anxiety as
      perceived by themselves and their mothers relative to the normative sample.
      Results also revealed low overall mother-child correspondence on child anxiety,
      particularly for mothers reporting more anxiety in themselves. Additionally,
      while age, gender, and socioeconomic status were not associated with mother-child
      correspondence, an unexpected relationship between race and correspondence
      emerged. Overall, our findings indicate that reliance on parents' perceptions of
      child anxiety prior to an invasive medical procedure is not sufficient.

PMID- 7830214
TI  - An evaluation of enhanced self-regulation training in the treatment of childhood
      obesity.
AB  - Obese children (8-13 years old) and at least one of their parents participated in
      a behaviorally oriented treatment program. Participants in a standard treatment
      condition experienced a multicomponent intervention in which parents were given
      primary responsibility for following program prescriptions. An enhanced child
      involvement condition provided the same basic intervention but with greater
      emphasis on, and training in, child self-regulation. Children in both conditions
      achieved a significant reduction in percentage overweight and triceps skin-fold
      during the 6-month treatment period. Overall, the follow-up period of 3 years was
      characterized by increases above posttreatment levels. There was, however, some
      suggestion in the 3-year follow-up results and the long-term patterns over a 6
      1/2-year period of the benefits of the enhanced child involvement approach.
      Findings are discussed in terms of suggestions for reconsideration of treatment
      goals, improved interventions, and refinements in the assessment of self
      regulatory behavior.

PMID- 7830215
TI  - Modifying problematic mealtime interactions of children with cystic fibrosis and
      their parents via behavioral parent training.
AB  - Implemented behavioral parent training targeting maladaptive mealtime behavior
      with two children with cystic fibrosis (CF) and their parents. Treatment was
      implemented in multiple baseline fashion across the two families. Primary
      dependent measure was coding of parent and child behaviors from videotaped
      dinners. Data were also collected on the children's daily calorie intake and
      weight. During treatment and at the posttreatment follow-ups, parents' attention
      to disruptive behavior decreased, attention to appropriate eating increased, and
      parental control at meals increased. The children showed an increase in
      appropriate behavior and a decrease in disruptive behavior; caloric intake and
      weight also improved. Results are discussed in terms of the applicability of
      behavioral intervention with feeding problems in children with CF.

PMID- 7830216
TI  - Race and sex differences in health locus of control beliefs and cardiovascular
      reactivity.
AB  - Examined the effects of race, sex, health locus of control (HLC), and the
      interactions of these variables on cardiovascular reactivity in 214 children.
      Participants completed the Multidimensional HLC scales for children. Systolic and
      diastolic blood pressures were measured at rest and during a reactivity task.
      Black boys had significantly higher scores on the powerful others (external HLC)
      subscale (p < 0.01) than white boys and girls. Furthermore, black boys showed
      greater systolic blood pressure reactivity when they were low on internality (vs.
      high) as compared to the other race-sex groups. Social and cultural factors may
      explain these differential findings across race and sex.

PMID- 7830217
TI  - Behavioral phenotype in children with Turner syndrome.
AB  - Compared Child Behavior Checklist results in 103 girls with Turner syndrome (TS)
      ages 7 to 13 years and 52 age-matched normal girls. Subjects with TS were part of
      a national study in Canada to evaluate growth hormone therapy in TS. Present data
      were obtained at baseline. Girls with TS scored below the comparison group in
      Total Social Competence (p < .0001), and above it in Total Behavior Problems (p <
      .05), Social (p < .0001), and Attention Problems (p < .001) scales. Item analysis
      revealed that subjects with TS were more immature, hyperactive, and nervous, and
      had poorer peer relations, greater difficulty at schooling, and more problems
      concentrating. In children with TS, height was correlated with social competence
      while karyotypes involving structural abnormalities of the X chromosome were
      associated with more behavior problems than a missing X or mosaicism.

PMID- 7830218
TI  - Nutritional status of Northwest Indiana Hispanics in a congregate meal program.
AB  - Rapid growth in the Hispanic elderly population, coupled with their unique needs,
      necessitates increasing their numbers in Title III(C) meal programs. This study
      assessed the nutritional adequacy of the diets of 49 Northwest Indiana congregate
      meal participants by evaluating: (1) their 1-day food records, and (2) the
      contributions of the site meal to daily intake. Mean daily total nutrient
      intakes, except for energy intake by the men, exceeded 67% of the Recommended
      Dietary Allowances (RDAs); however, only 22% of individual diets met this
      standard. Mean site meal nutrient intakes, aside from energy and magnesium by
      men, exceeded the recommended one-third of the RDAs, and contributed 42-73% of
      most nutrients to the daily intake despite the fact that the majority of the
      recipients refused one or more offered site meal components. Results of this
      study verify the importance of the role of congregate meals in providing
      nutritional adequacy to diets of Hispanic elderly and can be useful in menu and
      program planning for this population.

PMID- 7830219
TI  - Effectiveness of a nutrition education and physical fitness training program in
      lowering lipid levels in the black elderly.
AB  - A multidisciplinary nutrition education and fitness training program was tested
      for its effectiveness in lowering lipid profiles of elderly clients through
      dietary modification and exercise. The program served 31 free-living,
      predominantly female, black elderly aged 56-88 years. Dietary, anthropometric,
      biochemical, and fitness assessments were performed before and after the 10-week,
      biweekly program. Significant decreases (p < 0.05) were seen in waist
      circumference, total cholesterol (TC), low-density lipoproteins (LDL-C), and
      TC/HDL-C ratio. These findings suggest a 10-week, biweekly program can be
      effective in producing both significant, as well as favorable changes, in
      atherogenic lipids in elderly black subjects.

PMID- 7830220
TI  - Selected nutrient intakes and blood serum mineral concentrations of elderly
      humans fed regular and sweet acidophilus milks.
AB  - Calorie, protein, fat, calcium, phosphorus and manganese intakes were
      retrospectively calculated from the self-recorded intakes of 12 elderly humans,
      who were fed regular and sweet acidophilus milks in addition to their normal free
      choice diets. Blood serum of the subjects was analyzed for total calcium, ionized
      calcium, phosphorus and manganese at the beginning of the study, at cross
      overtime of milk treatments and at the end of the study. Total serum calcium,
      serum ionized calcium and phosphorus levels of the subjects were significantly
      higher at the end of the eight week study compared to pre-study levels (p <
      0.05). The kind of milk had no effect on serum levels of total calcium, ionized
      calcium, phosphorus and manganese. High dietary levels of calcium and phosphorus
      had no significant effect on serum manganese concentrations.

PMID- 7830221
TI  - P.E.P.: a partnership to assess and modify nutrition behavior in older adults.

PMID- 7830222
TI  - Influence of nutritional intake on 6-year mortality in an Italian elderly
      population.
AB  - Many observations agree on the existence, in older ages, of nutritional
      deficiencies secondary to dietary intake. This study investigated to what extent
      dietary intake of calories, protein, iron and vitamins influences the 6-year
      mortality in an elderly population living at home. To prevent the confounding
      effect of non-dietary factors, such as gender, functional and health status,
      socio-economic conditions and health risk habits, these variable have also been
      considered. The dietary intake was calculated comparing the content of nutrients
      in self-reported, 24-hour diet, with the 1980 Recommended Dietary Allowances
      (RDA) obtaining a percentage for each nutrient. The percentage difference from
      the RDA was tested on 6-year mortality using a bivariate regression model. The
      intake of protein, vitamin A, thiamin, niacin, vitamin B6 and folate was
      significantly related to mortality: subjects with a lower dietary intake of those
      nutrients had a higher risk of death. When nutrient intake was tested in a
      multiple regression model, adjusted for non-dietary potential confounders, only
      folate was an independent predictor of mortality. This study shows that most of
      the dietary nutrient's intake is related to socio-economic and physical factors.

PMID- 7830223
TI  - The farmers' market coupon program for low-income elders.
AB  - The Massachusetts Farmers' Market Coupon Program provides coupons to low-income
      elders redeemable for fresh produce at farmers' markets. The program was
      conceived to create new direct marketing opportunities for small farmers, while
      at the same time introducing people at nutritional risk to farmers' markets. This
      article reports on the results of an evaluation of the program by participating
      elders and draws conclusions regarding program successes based on the data.

PMID- 7830224
TI  - Writing equipment specifications to get what you need.

PMID- 7830225
TI  - Individual foods and food group patterns of the oldest old.
AB  - This study compares the dietary patterns of centenarians (n = 85) with
      sexagenarians (n = 76) and octogenarians (n = 83). A Daily Diet Diary was
      developed to code the responses of the 24-hour dietary recalls. Centenarians and
      octogenarians consumed a more varied (P < 0.05) diet, with higher (P < 0.01)
      consumption frequencies of milk and grains, and fewer (P < 0.01) skipped
      breakfasts than sexagenarians. However, centenarians also consumed high fat foods
      (P < 0.01), such as whole milk and biscuits, and coffee (P < 0.5) more frequently
      than the two younger cohorts. Several of the variations found in the food
      patterns among the three age groups may reflect cohort differences, rather than
      true antecedents for longevity.

PMID- 7830226
TI  - An examination of demographic, socio-cultural, and health differences between
      congregate and home diners in a senior nutrition program.
AB  - Building upon prior research, this study investigates characteristics of
      participants in a senior nutrition program in Hillsborough County, Florida. The
      Senior Citizens Nutrition and Activities Program serves approximately 2,600 meals
      per day to county residents 60 years of age and over. In this study, a sample of
      1,071 participants are surveyed for background characteristics, interpersonal
      relationships and emotional closeness, health and economic condition, emotional
      condition, and participation in the program. Crosstabular analyses are performed
      on the collected data with age, sex, and race controlled. The results indicate
      that the program is reaching its goals of promoting good health among the older
      population of Hillsborough County by providing nutritious meals and reducing
      social isolation, which often accompanies aging.

PMID- 7830227
TI  - Cross-cultural counseling.

PMID- 7830228
TI  - Difficulties in assessing drug/food interactions from chart audit in an elderly
      Barbadian sample group.
AB  - The aim of this study was to examine the prevalence of potential drug/food
      interactions among 290 elderly Barbadian outpatients. These findings indicate
      that chart audit is insensitive to definite interactions but was able to detect
      the prevalence of potential interactions (1.38 per outpatient). The risk of
      potential interactions was significantly higher among outpatients who were older,
      female, and those who used a larger number of prescribed medications. There were
      no significant differences in the prevalence of potential interactions among
      diabetics and nondiabetics. The findings indicate that the absence of relevant
      data on patients' symptoms, and anthropometric and laboratory measures in more
      than 80% of patients' charts makes it impossible to assess the prevalence of
      definite drug/food interactions from chart audit. Weight changes, nutrient
      levels, and symptoms were the most frequently missing data. Chart audit is
      therefore an invalid and unreliable approach to estimate definite drug/food
      medications.

PMID- 7830229
TI  - An improved method of documenting and evaluating nutritional intake of persons
      with Alzheimer's disease.

PMID- 7830230
TI  - Liposomes as carriers for topical and transdermal delivery.
AB  - The delivery of active agents to the skin by liposome carriers is an
      interdisciplinary topic of great interest today. Data accumulated over the last
      decade strongly point to important advantages of these drug delivery systems. A
      symposium devoted to classic and new approaches in the use of liposomal systems
      was organized and chaired by M. Mezei and E. Touitou as a part of the Jerusalem
      Conference on Pharmaceutical Sciences and Clinical Pharmacology, held on May 24
      30, 1992, in Jerusalem, Israel. The presentations focused on liposomes as tools
      in the mechanistic study of absorption promoters (T. Nagai), drug liposomal
      delivery in the skin strata and structures (N. Weiner), interaction of liposomes
      and niosomes with the human skin (H.E. Junginger), and design and
      characterization of caffeine liposomal systems for use in hyperproliferative
      diseases (E. Touitou). Mezei reviewed biodisposition and clinical studies on
      liposomal dosage forms containing various drugs.

PMID- 7830231
TI  - Discrimination and direct determination of cephalosporins by circular dichroism.
AB  - The circular dichroism and ultraviolet spectra of 15 commercial cephalosporins in
      common clinical use are analyzed. Distinguishing between the beta-lactam
      antibiotics (penicillins, cephalosporins, and cephamycins) on the basis of their
      CD spectral data has been found to be straightforward. Furthermore, sufficient CD
      spectral dissimilarities are observed to discriminate among the cephalosporin
      homologues and to classify these antibiotics in five spectroscopic groups, on the
      basis of the wavelengths of their Cotton effects. In addition, some chemical
      structural characteristics for these spectroscopic groups are discussed. Besides
      molar absorptivity and CD data, the slopes and the intercepts of the equations of
      the regression line are calculated for each of these antibiotics, the correlation
      coefficients being higher than 0.9993. The validity of the proposed model is
      confirmed by analysis of the variance. The results demonstrated that the proposed
      method is accurate and precise. The method was successfully applied to the direct
      determination of these drugs in commercial oral suspensions, injections, and
      capsules. The principal advantages of this method are quickness and simplicity no
      derivatization or chromatographic separation steps being needed.

PMID- 7830232
TI  - Dissolution kinetics of griseofulvin in mixed micellar solutions.
AB  - The dissolution kinetics of the poorly water soluble, lipophilic model drug
      substance griseofulvin were studied in solutions containing simple and mixed
      micelles of sodium cholate (BS) and phosphatidylcholine (PC). Variables under
      investigation were the concentration of BS and the ratio PC/BS. A rotating disk
      apparatus was used to monitor the dissolution process. With this method, (mixed)
      micellar diffusion coefficients could be calculated and some detailed information
      about the physicochemical behavior and composition of mixed PC/BS micelles could
      be derived.

PMID- 7830233
TI  - N-methyl-2-pyrrolidone as a cosolvent: relationship of cosolvent effect with
      solute polarity and the presence of proton-donating groups on model drug
      compounds.
AB  - N-Methyl-2-pyrrolidone (methylpyrrolidone), a cosolvent which has been used in
      veterinary medicine and in transdermal delivery devices, was investigated as a
      cosolvent for model drug compounds of widely varying polarity. These compounds
      were digoxin, sulfamethoxazole, hydrocortisone acetate, theophylline, phenytoin,
      and reserpine. Methylpyrrolidone was found to be an extremely efficient cosolvent
      for low solubility polar drugs such as digoxin or drugs containing multiple
      proton-donating groups such as phenytoin. The increase in solubility observed in
      aqueous solutions of digoxin and phenytoin to which 0.2 volume fraction of
      methylpyrrolidone was added was 500x and 65x, respectively. Significant
      deviations from log-linear solubilization were observed with digoxin,
      sulfamethoxazole, phenytoin, and reserpine, indicating significant water-solute
      cosolvent interactions.

PMID- 7830234
TI  - Anti-invasive activity of 3,7-dimethoxyflavone in vitro.
AB  - Invasion of MCF-7/6 human mammary carcinoma cells into embryonic chick heart
      fragments was studied in organ culture during 8 days. The effect of 31
      polyphenolic compounds, belonging to the flavonoids, chalcones, or coumarins, was
      tested in this assay for invasion. The anti-invasive activity of 3,7
      dimethoxyflavone was found at concentrations ranging from 1 to 100 microM. At
      these anti-invasive concentrations, no cytotoxic effects could be detected: the
      anti-invasive effect was reversible upon omission of the molecule from the
      medium, and treatment of MCF-7/6 cells or heart fragments did not affect
      subsequent outgrowth from explants on tissue culture plastic. The molecule did
      not inhibit growth of MCF-7/6 cell aggregates nor of heart fragments kept in
      suspension culture. The action mechanism of 3,7-dimethoxyflavone is the subject
      of our ongoing research.

PMID- 7830235
TI  - Synthesis of the cholesteryl ester prodrugs cholesteryl ibuprofen and cholesteryl
      flufenamate and their formulation into phospholipid microemulsions.
AB  - Phospholipid micoremulsions have been suggested as a drug-delivery system for
      hydrophobic compounds. In this study hydrophobicity was achieved by derivatizing
      with cholesterol. Cholesteryl ibuprofen (3) and cholesteryl flufenamate (4) were
      synthesized. 3 was isolated as an amorphous, white solid with a melting range of
      114-120 degrees C. 4 was isolated as a crystalline, white solid with a melting
      range of 145-148 degrees C. The proposed structures of 3 and 4 were supported by
      IR, NMR, MS, and organic microanalysis. Phospholipid:cholesteryl ester
      microemulsions were prepared by the addition of a 1-propanol solution of the
      cholesteryl ester, other lipids, and phospholipid to a rapidly mixing KCl/KBr
      solution. The hydrophobic phase was modified by the addition of cholesteryl
      oleate or triolein to study the effect of the fluidity of the hydrophobic core on
      the formation of the microemulsions. The results indicated that a molar ratio of
      75:25 and a total lipid concentration of 60 mg/mL consistently gave
      microemulsions with a mean size of 100-150 nm. In addition, the formation of
      eutectic mixtures of 3 and 4 with cholesteryl oleate were determined to be 16%
      (w/w) for 3 and 12% (w/w) for 4; melting points were 35.2 and 45.2 degrees C,
      respectively. The solubilities of 3 and 4 in triolein were determined to be 13.2%
      (w/w) and 11.5% (w/w), respectively. Other investigators have shown that if the
      core of a phospholipid:cholesteryl estermicroemulsion exists in a liquid state at
      physiologic temperature, the turnover of the cholesteryl esters from these
      microemulsions occurs at a faster rate.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7830236
TI  - A comparison of in vitro skin-penetration cells.
AB  - A new low-volume flow-through diffusion cell (LVFC) was designed to provide
      accurate determinations of penetrant flux across skin while minimizing the
      dilution of penetrant in receptor fluid and eliminating the need for magnetic
      stirring. The performance of the 0.3-mL LVFC was compared to a magnetically
      stirred, 4.3-mL high-volume flow cell (HVFC) and to a magnetically stirred,
      manually sampled 7.5-mL static cell (SC) with hydrophilic and lipophilic
      penetrants. The clearance of 14C-labeled benzoic acid from the LVFC and HVFC
      followed an exponential profile expected for complete mixing when the LVFC and
      HVFC were run at flow rates of 0.4-0.9 and 4.0-5.2 mL/h, respectively. The in
      vitro dispositions of 14C-labeled benzoic acid and estradiol were determined in
      the LVFC and HVFC by applying the compounds to split-thickness pig skin at a 4
      micrograms/cm2 dose. Additionally, the effects of receptor fluid flow rate (1.2
      vs 3.5 cell volumes/h) and method of skin attachment (O-ring vs compression) were
      determined on disposition in the HVFC. The percutaneous penetration of benzoic
      acid and the residue of estradiol within skin did not differ between the LVFC and
      HVFC. However, the percutaneous penetration of benzoic acid increased
      significantly (p < 0.05) using the O-ring attachment as compared to compression
      at a flow rate of 1.2 cell volumes/h. The in vitro permeation of benzoic acid
      saturated water and 17 beta-estradiol-saturated propylene glycol monolaurate
      through human epidermis was compared between the LVFC, HVFC, and SC. The LVFC and
      HVFC had flow rates of 0.9-1.0 mL/h.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7830237
TI  - Multiple-dose pharmacokinetics of ceftibuten after oral administration to healthy
      volunteers.
AB  - The pharmacokinetics of ceftibuten in plasma and urine were investigated after
      oral administration. Twelve healthy subjects were treated orally twice daily with
      400 mg of the drug for 7 days; on day 8, the subjects received a last dose of 400
      mg of ceftibuten. Ceftibuten and its metabolite, the trans isomer of ceftibuten,
      were assayed in plasma and urine by a specific HPLC method with UV detection.
      Ceftibuten was rapidly absorbed, as evidenced by the mean time to the maximum
      observed cis-ceftibuten concentration of 2.4 h. To describe the drug intake
      process, a Weibull model was used. For the metabolite, the mean time to maximum
      concentration in plasma was 3.25 h. Mean values for the terminal half-life in
      plasma were 2.17 h for cis-ceftibuten and 3.19 h for trans-ceftibuten. The
      overall elimination half-life, tmax, and total and renal clearances of cis
      ceftibuten were invariant with respect to duration of dosing. The area under the
      plasma concentration versus time curve from 0 to infinity and the Cmax of this
      drug were significantly higher on day 8 than the values predicted from the
      elimination half-life computed on day 1 of treatment and the dosing interval. The
      pharmacokinetic parameters of trans-ceftibuten were invariant with respect to
      duration of dosing. Ceftibuten was well tolerated; there were no clinically
      significant adverse clinical events. The results from the present study indicate
      that the levels of cis-ceftibuten in plasma as well as in urine remain above the
      MICs for susceptible organisms over the dosing interval.

PMID- 7830238
TI  - Bioavailability and disposition of terodiline in man.
AB  - Terodiline was concomitantly administered intravenously (12.5 mg) and orally
      ([2H]terodiline, 12.5 mg) to 10 healthy volunteers. In four of the subjects, a
      tracer dose of the intravenously given terodiline was 3H-labeled. In a separate
      study, six subjects were given [3H]terodiline orally. Estimated pharmacokinetic
      parameters were as follows: systemic clearance, 93 mL/min; renal clearance, 14
      mL/min; volume of distribution at steady-state, 407 L; terminal half-life, 54 h;
      and mean residence time, 77 h. After intravenous infusion, a rapid distribution
      phase (half-life, 4.5 min) could be observed. The maximum serum concentration
      after the oral dose was 29 micrograms/L and the time to maximum concentration was
      5 h (estimated by noncompartmental analysis). Absorption commenced within the
      first hour and by deconvolution the maximum rate of absorption was determined to
      occur between 1 and 3 h, and by 3.4 h 90% of the available dose had been
      absorbed. Calculation of bioavailability by noncompartmental AUC, two
      compartmental analysis, urinary excretion, and 24-h oral/intravenous
      concentration ratio gave similar results (ANOVA test, not significant). About 75%
      and 25% of administered radioactivity could be recovered in urine and feces,
      respectively. Intact terodiline in feces accounted for about 1% of the dose. p
      Hydroxyterodiline was quantitated in feces and accounted for about 5% of the
      dose. Another metabolite, 3,4-dihydroxyterodiline, which has not previously been
      detected in urine or serum, was also identified.

PMID- 7830239
TI  - Different stereospecific protein binding of tetrahydrofolates to human serum
      albumin.
AB  - The protein binding of the tetrahydrofolates folinic acid (FA) and its metabolite
      5-methyltetrahydrofolic acid (5-MTHF) to human serum albumin (HSA) is
      stereoselective. At therapeutically relevant concentrations of tetrahydrofolate
      (range, 5-100 microM), the protein binding was stereoselective to the (R)-isomers
      of FA and 5-MTHF. The binding of (R)-FA and (R)-5-MTHF was saturated at a
      concentration of 7% HSA [(R)-tetrahydrofolate bound, ca. 80%]. In contrast to (S)
      FA, which was not bound to HSA, (S)-5-MTHF was bound to 45% under physiological
      conditions. (R)-FA did not influence the protein binding of (S)-FA.
      Hypoalbuminemia is common in patients with advanced colorectal cancer and affects
      differentially the protein binding of the diastereoisomers of FA and 5-MTHF.
      Thus, an influence on the biochemical modulation of 5-fluorouracil by
      tetrahydrofolates should be taken into consideration.

PMID- 7830240
TI  - Trace decomposition of selegiline. Use of worst-case kinetics for a stable drug.
AB  - A solution of selegiline hydrochloride reference standard, which contained no
      detectable impurities at the time of its preparation, was found by HPLC to
      contain a trace of a compound at the locus of methamphetamine when analyzed after
      1 year. Heating selegiline solutions at pH 7 and 105 degrees C produced
      methamphetamine as the major product at a rate which closely followed the first
      order rate equation. Using only these data and worst-case assumptions, rate
      constants were estimated at various temperatures; the activation energy was
      estimated to be about 25 kcal, and the stability-indicating validity of the assay
      used was reaffirmed. Selegiline undergoes degradation at a negligibly slow rate.

PMID- 7830241
TI  - Crystal and molecular structures of tricyclic neuroleptics.
AB  - The X-ray crystal structures of three tricyclic neuroleptics have been completed
      and are reported herein. These include amitriptyline hydrochloride (I),
      chlorprothixene hydrochloride (II), and ethopropazine hydrochloride (III). The
      structures were compared with the structures of similar molecules with similar
      pharmacological activity. It was found that there is a great deal of flexibility
      in the structures of these molecules, which makes it difficult to determine the
      pharmacologically active conformations. Crystallographic data: (I) C20H24NCl,
      monoclinic space group P2(1)/a, a = 13.812(4) A, b = 9.140(2) A, c = 14.345(4) A,
      beta = 96.82(2) degrees, Z = 4, final R = 0.059 for 1630 observed (l > 3
      sigma(l)) reflections. (II) C18H20NSCl2.CHCl3, monoclinic space group C2/c, a =
      29.416(4) A, b = 6.986(1) A, c = 23.374(3) A, beta = 109.78(1) degrees, Z = 8,
      final R = 0.046 for 1436 observed reflections. (III) C19H25N2SCl, monoclinic
      space group P2(1)/c, a = 8.849(1) A, b = 14.475(2) A, c = 14.832(1) A, beta =
      98.72(1) degrees, Z = 4, final R = 0.039 for 2583 observed reflections.

PMID- 7830242
TI  - Hydrogen bonding. 33. Factors that influence the distribution of solutes between
      blood and brain.
AB  - It is shown that neither the set of directly determined blood-brain concentration
      ratios (BB) of Young and Mitchell nor the set of indirectly obtained values of
      Abraham and Weathersby are suitable for the construction of a general equation
      for the interpretation and prediction of log BB values. However, combination of
      both sets leads to the general equation log BB = -0.038 + 0.198R2 - 0.687 pi H2 -
      0.715 alpha H2 - 0.698 beta H2 + 0.995Vx (n = 57, rho = 0.9522, sd = 0.197, F =
      99.2), where the solute descriptors are R2, an excess molar refraction; pi H2,
      the dipolarity/polarizability, alpha H2 and beta H2, the effective or summation
      hydrogen-bond acidity and basicity; and Vx, the characteristic volume of McGowan.
      Thus solute dipolarity/polarizability, hydrogen-bond acidity, and hydrogen-bond
      basicity favor blood, and solute size, as Vx, favors brain. Methods are given for
      the estimation of solute descriptors through fragment schemes, so that log BB
      values themselves may be obtained simply from knowledge of solute molecular
      structure.

PMID- 7830243
TI  - Vibrational and NMR spectroscopic study of aged flurazepam mono- and
      dihydrochloride salts for content identity.
AB  - Archival samples of flurazepam monohydrochloride and "hydrochloride" (i.e., the
      dihydrochloride) were examined by Fourier transform infrared and Raman
      spectroscopy to determine evidence of degradation during storage for 13-15 years.
      No degradation of the three different batches of monohydrochloride salts was
      detected, but various degrees of degradation of the eight specimens of flurazepam
      hydrochloride diprotonated salts were indicated by enhanced intensities (IR 1635,
      1509, 1226; Raman 1636, 1408, 1149 cm-1) and new features (IR 1742, 943, 755;
      Raman 1554, 837, 742 cm-1). All of these features, except the 1742 cm-1 IR band,
      were attributed to the presence of the hydrolysis product 5-chloro-2-[[2
      (diethylamino)ethyl]amino]-2'-fluorobenzophenone hydrochloride whereas the 1742
      cm-1 band was attributed to glycine hydrochloride, the other hydrolytic moiety.
      The flurazepam hydrochloride samples were also examined in deuterated dimethyl
      sulfoxide solution by proton nuclear magnetic resonance (1H-NMR) spectroscopy to
      verify the presence of the degradation products and to estimate the levels of
      degradation (approximately 3-36%) of the drug. IR and Raman spectra of the
      "benzophenone" hydrochloride in the "fingerprint" region are compared with two
      samples of flurazepam dihydrochloride (slightly and highly degraded) and their
      features discussed. Vibrational assignments are made and discussed for the
      observed IR and Raman wavenumbers for the "benzophenone" hydrochloride.

PMID- 7830244
TI  - pH-metric log P. 4. Comparison of partition coefficients determined by HPLC and
      potentiometric methods to literature values.
AB  - The pKa and log P of 20 compounds, including six substituted phenols, two
      substituted quinolines, N-methylaniline, five barbiturate derivatives, two
      phenothiazines, and several other molecules of pharmaceutical interest, were
      determined by the potentiometric technique at 25 degrees C and ionic strength 0.1
      M (KNO3). The log P values were determined also by partition HPLC. Three of the
      substances were of very low aqueous solubility, and for these the aqueous pKas
      were determined by extrapolation from methanol-water solutions using the Yasuda
      Shedlovsky technique. Values of log P obtained both by potentiometry and by
      partition HPLC, which ranged from 0.3 to 5.4, were in very good acordance with
      literature values. The general applicability of the potentiometric technique to
      ionizable compounds of diversely varied structures was demonstrated by the study.

PMID- 7830245
TI  - Photolytic destruction and polymeric resin decontamination of aqueous solutions
      of pharmaceuticals.
AB  - Amoxicillin, ampicillin, bleomycin, carmustine, cephalothin, dacarbazine,
      lomustine, metronidazole, norethindrone, streptozocin, sulfamethoxazole, and
      verapamil were completely degraded in solution, without the production of
      mutagenic residues, by photolysis using a medium-pressure mercury lamp in an all
      quartz apparatus. A stream of air was passed through the solution and for
      amoxicillin, ampicillin, bleomycin, lomustine, metronidazole, and norethindrone
      it was necessary to add hydrogen peroxide. Dilute aqueous solutions of
      ampicillin, bleomycin, carmustine, cephalothin, lomustine, norethindrone,
      streptozocin, trimethoprim, and verapamil can be decontaminated using polymeric
      Amberlite resins.

PMID- 7830246
TI  - Comparison of quantitative whole-body autoradiographic and tissue dissection
      techniques in the evaluation of the tissue distribution of [14C]daptomycin in
      rats.
AB  - Quantitative whole-body autoradiography (QWBA) was evaluated and compared to
      tissue dissection/liquid scintillation counting (TD/LSC) techniques by
      determining the tissue distribution of radiocarbon in rats following iv
      administration of the antibiotic [14C]daptomycin (LY146032). QWBA, using computer
      assisted video-image analysis, was initially evaluated by characterizing and
      calibrating commercial standards to blood and brain, kidney, liver, and lung
      homogenates. Frozen (carboxymethyl)cellulose blocks containing tissue homogenates
      spiked with [14C]glucose (370-37,000 Bq/g or 10-1000 nCi/g) were sectioned and
      optical densities (OD) measured. Characterization of QWBA included repeated
      measures data analysis to determine the significance of tissue type and intra-
      and inter-section and block variability. Regression models relating OD to
      radiocarbon concentration were also used to calibrate commercial standards for
      use in QWBA analyses. Results indicated that there were no substantial
      differences between OD readings from different tissues; however, the greatest
      source of variation in OD reading was section thickness. Because quantitative
      variations were largely attributed to section thickness, an internal standard
      (IS), consisting of liver homogenates spiked with [14C]glucose, was evaluated as
      a correction factor. Tissue concentrations of radiocarbon in male Fischer 344
      rats were evaluated by QWBA and TD/LSC techniques 0.25 h following a single iv 10
      mg/kg dose of [14C]daptomycin. Results indicated that tissue concentrations of
      radiocarbon obtained by QWBA, normalized using an IS, were comparable to those
      obtained by TD/LSC.

PMID- 7830247
TI  - Significance of viable skin layers in percutaneous permeation and its implication
      in mathematical models: theoretical consideration based on parameters for
      betamethasone 17-valerate.
AB  - The role of viable skin layers (viable epidermis and dermis) is examined by the
      three-layer model using parameter values for betamethasone 17-valerate. The
      mathematical three-layer diffusion model indicates that the lag time and half
      life after vehicle removal in epidermis and split-thickness skin are longer than
      those in stratum corneum without viable layers, even if drug flux at steady-state
      is minimally altered. The theoretical values of the lag time and half-life
      predicted for epidermis and split-thickness-skin samples are compatible with the
      values observed in another in vitro study. The results predicted by the three
      layer model indicate that the simplified model (single-layer or compartment
      model), which regards the whole skin as one diffusion layer or one compartment,
      may be warranted because all three skin layers have the same half-life after
      vehicle removal. The parameters used in the simplified model are estimated from
      some of the following values directly obtainable in the experiment: flux from
      skin and amount in the whole skin at steady-state, lag time, and drug
      concentration or amount maintained to be unchanged in the donor site. However,
      the simplified model often cannot resolve some discrepancy between the data and
      model (e.g., the ratio of the half-life to lag time) even if the data may be
      explained by the three-layer model.

PMID- 7830248
TI  - Pharmacokinetics of paeonol after intravenous administration in rats.
AB  - A simple high-performance liquid chromatography methodology was developed to
      study the pharmacokinetics of paeonol in the rat after intravenous (iv) bolus
      administration of various doses (2.5, 5, or 10 mg/kg). The pharmacokinetics of
      paeonol in rat plasma at each dose were well described by a two-compartment
      model. The area under the curve increased proportionally with dose and
      consequently total body clearance was independent of dose. There was no dose
      related difference in the elimination half-life or volume of distribution. These
      results indicate that the pharmacokinetics of paeonol after iv administration are
      linear over the 2.5-10 mg/kg dose range.

PMID- 7830249
TI  - Determination of enantiomers in ephedrine mixtures by polarimetry.
AB  - Enantiomeric purities have been measured with precisions that are equivalent to
      those obtained from chiral chromatography by a simple ligand substitution
      reaction into the first coordination sphere of Cu(II)-tartrate complexes. The
      model systems are binary mixtures of the ephedrines. Ligand exchange reactions
      are done in bulk aqueous media. The detector is polarimetry. Multivariate
      regression analyses of optical rotation data measured at five wavelengths are
      used to prepare calibration and prediction models for binary mixtures of the
      enantiomers.

PMID- 7830250
TI  - A linear theory of transdermal transport phenomena.
AB  - A theory of charge, fluid-mass, and solute (including macromolecular) transport
      through porous media is applied to describe transport phenomena across the
      external layer of mammalian skin. Linear relationships are derived between
      transport fluxes and applied fields. These relationships introduce six effective
      transdermal transport coefficients. Formulas for each of these coefficients are
      provided. The practical relevance of these parameters is emphasized in the
      specific context of transdermal drug delivery. By employing typical physiological
      values for the various geometrical and physicochemical parameters that appear in
      the formulas for the transdermal transport coefficients, predictions are made for
      transport rates of charge, fluid mass, and solute species across a uniform
      thickness skin sample contained within a diffusion-cell apparatus. These results
      are used to explore transdermal phenomena involving forced convection, current
      flow, electroosmosis, iontophoresis, and molecular diffusion (including
      convective dispersion). Comparisons with existing transdermal drug delivery data
      are made. On the basis of these comparisons, the theory suggests that transdermal
      transport in the presence of an electrical field may occur through corneocytes of
      the stratum corneum. The theory confirms the importance of a shunt route for
      small ion transport, as well as an intercellular route of transport for passive
      diffusion of noncharged substances. These latter conclusions, also based on
      comparisons with experimental data, are consistent with previous statements in
      the literature. A new form of solute transport enhancement, termed transdermal
      convective dispersion, is included in the theory, and methods for its measurement
      are described. Generalizations and future applications of the theory are
      discussed.

PMID- 7830251
TI  - Intestinal permeability of ophthalmic beta-blockers for predicting ocular
      permeability.
AB  - The purpose of this study was to investigate the intestinal permeability of
      ophthalmic beta-blockers and evaluate the utility of intestinal membrane for
      predicting the ocular permeability. The penetrations of beta-blockers were
      measured across the isolated jejunum and colon of the albino rabbit using a two
      chamber glass diffusion cell. beta-Blockers tested include atenolol, carteolol,
      tilisolol, timolol, and befunolol. Colonic membrane showed lower permeability of
      hydrophilic drugs than jejunal membrane. Scraping the entire cell monolayer of
      jejunum increased the drug permeability. There was a significant correlation
      between colonic permeability coefficients and lipophilicities of beta-blockers.
      The permeability coefficients through jejunum and scraped jejunum were not
      susceptible to drug lipophilicities. Jejunum, scraped jejunum, and colon showed
      permeability coefficients almost equal to those of sclera, conjunctiva, and
      cornea, respectively. There was a significant correlation between permeability
      coefficients through colon and cornea. These results indicate that the steady
      state permeability of ophthalmic beta-blockers through ocular membranes may be
      predicted by measuring the permeability through certain intestinal membranes.
      However, the analyses of intestinal permeability using Fick's equation showed the
      functional difference of intestinal permeability from ocular permeability of
      ophthalmic beta-blockers.

PMID- 7830252
TI  - Measurement of pharmacodynamic effects of dexamethasone on epidermis by
      phosphorus nuclear magnetic resonance spectroscopy in vitro.
AB  - An intact, viable epidermal preparation was perfused and phosphoenergetic and
      phospholipid metabolite levels were measured by 31P NMR. The preparation was
      stable in the NMR perfusion apparatus for 24 h. The effects of inclusion of
      ethanolamine and dexamethasone-21-acetate in the perfusion media on phosphorus
      containing metabolites was assessed by examination of serial 31P NMR spectra.
      Phosphomonoesters increased significantly during the fourth hour of perfusion
      with ethanolamine (3 mM) and remained elevated. A corresponding decrease in
      nucleotide triphosphates was noted, but phosphocreatine (PCr) remained unchanged.
      Dexamethasone perfusion resulted in a biphasic effect on phosphomonoester
      metabolism and a dose-dependent decrease in PCr and nucleotide triphosphate
      levels. A log-linear relationship was observed between dexamethasone dose in the
      1-100-nM range and a decrease in PCr. These techniques with an isolated intact
      epidermal preparation are useful for elucidating mechanisms of corticosteroid
      action on the skin and serve as a basis for developing a mechanistically relevant
      topical corticosteroid bioequivalence technique.

PMID- 7830253
TI  - In vitro corneal permeability of diclofenac sodium in formulations containing
      cyclodextrins compared to the commercial product voltaren ophtha.
AB  - The influence of different cyclodextrin derivatives on the in vitro permeability
      of diclofenac sodium through pig cornea was investigated and compared to the
      commercial product Voltaren ophtha. (Hydroxypropyl)-beta-cyclodextrin (HP beta
      CD) and two amorphous methylated cyclodextrins with different degrees of
      substitution were used. In hemolysis studies on human erythrocytes, the hemolytic
      activity of the different cyclodextrins and the drug was assessed. It was shown
      that HP beta CD reveals the most favorable toxicological properties. A decrease
      in the hemolytic activity of diclofenac was yielded by adding HP beta CD. In the
      permeability experiments the dependency of the permeability coefficients and lag
      times on the type of cyclodextrin and pH of the solutions were examined. A
      solution containing HP beta CD buffered in the pH range 6.5 to 7 is proposed as a
      useful eye drop formulation. All cyclodextrin formulations showed advantages as
      compared to Voltaren ophtha.

PMID- 7830254
TI  - Absorption of ACE inhibitors from small intestine and colon.
AB  - The intestinal absorption of two ACE inhibitors was studied to determine the
      potential for colonic delivery of small peptides. In addition, studies were also
      performed to assess intestinal tissue uptake and evaluate a canine intestinal
      access-port model as techniques for screening absorption. To evaluate the impact
      of differences in the contributions of passive permeation and carrier-mediated
      peptide transport on in vitro uptake and in vivo absorption, an esterified
      prodrug, benazepril, and a free diacid non-prodrug, CGS 16617, were selected for
      study. Potential colonic absorption enhancement utilizing coadministration of
      Intralipid was also investigated. Studies in rat everted intestinal rings
      verified that jejunal benazepril uptake included a carrier-mediated component
      while that of the diacid did not. Uptake of both drugs was purely passive in
      colonic rings. Equilibrium uptake and uptake rate of the more lipophilic prodrug
      was 2-fold greater than the diacid. Benazepril and CGS 16617 jejunal uptake rate
      at 0.01 mM was 3.5 and 2.5 times higher, respectively, than from colonic rings.
      Following jejunal administration in dogs, maximum benazepril plasma levels (Cmax)
      and area under the plasma level versus time curve (AUC) were 5.5 and 3.0 times
      higher, respectively, than following colonic administration. Maximum benazepril
      plasma levels following colonic administration in dogs was 2-fold greater than
      for CGS 16617, consistent with in vitro results. Colonic coadministration of the
      poorly-absorbed CGS 16617 with 2 mL of Intralipid (within dietary range for fecal
      fat content) enhanced Cmax and AUC 2.5- and 3.5-fold, respectively, in the dog
      and AUC 1.5-fold in the rat.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7830255
TI  - Isolation and structure elucidation of the major photodegradation products of
      pirmenol hydrochloride.
AB  - Column chromatography, thin-layer chromatography, high-performance liquid
      chromatography, nuclear magnetic resonance spectrometry, and high-resolution mass
      spectrometry were employed to separate and identify the photodegradation products
      of pirmenol hydrochloride [(+/-)-cis-alpha-[3-(2,6-dimethyl-1-piperidinyl)propyl]
      alpha-phenyl-2- pyridinemethanol monohydrochloride monohydrate], a new
      antiarrhythmic drug. A methanol solution of pirmenol was irradiated using a low
      pressure mercury lamp. The solution afforded four major degradation products,
      three of which were identified as 3-(cis-2,6-dimethylpiperidinyl)propyl 2-(2
      pyridyl)phenyl ketone, 2-(2-pyridyl)benzoic acid, and methyl 2-(2-pyridyl)
      benzoate. The degradation followed apparent-first-order reaction kinetics. In
      addition, the possible photodegradation pathways are discussed with reference to
      reaction mechanisms.

PMID- 7830256
TI  - Formulation optimization of indomethacin gels containing a combination of three
      kinds of cyclic monoterpenes as percutaneous penetration enhancers.
AB  - A computer optimization technique based on response surface methodology was
      applied for the optimization of a hydrogel formulation containing indomethacin as
      a model drug. As the penetration enhancer, a combination of three cyclic
      monoterpenes, limonene, menthol, and cineole, was employed. Pharmacokinetic
      parameters, from an in vivo percutaneous absorption study on rats of model
      formulations prepared according to the composite experimental design for five
      factors, were determined as prime response variables. The skin damage evoked by
      each formulation was microscopically judged and graded as the response variable
      concerning skin safety. The response variables were predicted by multiple
      regression equations comprising combinations of the five formulation factors. The
      regression equations for the response variables assembled as a simultaneous
      optimization problem based on the generalized distance function. The simultaneous
      optimum was predicted as a function of individual optima within a 95% confidence
      region. The predicted response values for the optimum formulation have been
      successfully validated in a repeated in vivo percutaneous absorption study.

PMID- 7830257
TI  - Photorepair and excision repair removal of UV-induced pyrimidine dimers and (6-4)
      photoproducts in the tail fin of the medaka, Oryzias latipes.
AB  - Induction and repair of UV-B induced DNa damage in the tail fin of the Medaka,
      were examined immunohistochemicaly and by the enzyme-linked immunosorbent assay
      (ELISA). UV-induced DNA damage was detected only in the outermost layer of
      epithelial cells and did not differ in fishes having different degree of
      melanization. Both pyrimidine dimers and (6-4) photoproducts in the fin cells
      were removed by excision repair in the dark, the excision of (6-4) photoproducts
      being about twice as efficient as that of pyrimidine dimers. The rate of excision
      repair of UV-induced lesions in fin tissue was three to four times that in
      cultured Medaka cells, OL32. In the fin cells, reductions in the numbers of
      pyrimidine dimers and (6-4) photoproducts were seen after treatment with
      fluorescent light, whereas less reductions of pyrimidine dimers and no reductions
      of (6-4) photoproducts were observed in OL32 cells.

PMID- 7830258
TI  - Timing in administration of a heat-killed Lactobacillus casei preparation for
      radioprotection in mice.
AB  - A single subcutaneous injection of a preparation of heat-killed Lactobacillus
      casei (LC 9018), given before or after irradiation, significantly increased the
      survival rate of mice that had received 8.5-Gy 137Cs whole-body gamma
      irradiation. A similar radioprotective effect was observed when LC 9018 was
      administered within the period from 2 days before irradiation to 9 h after
      irradiation, the pre-irradiation treatment being slightly better than the post
      irradiation treatment. Increases in the weight of the spleen and in the number of
      endogenous spleen colonies on days 8 and 12 after irradiation suggested that the
      radioprotective effect was based on enhanced recovery of hematopoietic tissues.
      The activity of macrophage colony-stimulating factor (M-CSF) in serum was rapidly
      increased by the treatment and was maintained at the elevated level for 13 days.
      At the same time, an increased level of M-CSF mRNA was detected in the livers of
      the treated mice. However, LC 9018 failed to save the lives of mice when
      administered 3 days after irradiation, although it increased serum M-CSF as
      effectively as noted above. The small advantage of the pre-irradiation over the
      post-irradiation treatment was not explained by the increases of metallothionein
      in the hematopoietic tissues of the treated mice.

PMID- 7830259
TI  - Radiation-chemical discussion on inverse dose-rate effect observed in radiation
      induced strand breaks of plasmid DNA.
AB  - Experimental results of inverse dose-rate effect, so-called Kada Effects, which
      was published by Takakura and her coworkers on radiation-induced strand breaks of
      plasmid DNA in aerated aqueous solution, have been kinetically analyzed and
      discussed on the basis of radiation chemistry, the kinetic analysis indicates
      that there are two possible mechanisms; 1) equilibrium mixture of O2- and HO2 is
      responsible for strand breaks of DNA, and 2) peroxyl radical produced from
      citrate is effective for the strand breaks. However, the detailed kinetic
      analysis revealed that the latter is improbable because unimolecular decay of the
      peroxyl radical must be assumed to be negligible for its participation despite
      fast decay of analogous organic peroxyl radicals. The analysis has also given
      9.93 +/- 0.10 dm3 mol-1 s-1 per nucleotide unit, which corresponds to 7.62 x
      10(4) dm3 mol-1 s-1 per DNA molecule, as the rate constant for the reaction of
      the equilibrium mixture with plasmid pBR 322 DNA. Furthermore the probability
      that the reaction of the mixture with a nucleotide unit of DNA leads to strand
      breaks was obtained to be 3.36 x 10(-3) for gamma-irradiated system and 1.98 x
      10(-3) for beta-irradiated system, respectively.

PMID- 7830260
TI  - Assignment of six patients with xeroderma pigmentosum in Hokkaido area to a
      variant form.
AB  - Six Japanese patients in Hokkaido area were diagnosed as xeroderma pigmentosum
      (XP) at two University Hospital; one patient, a 29 years old female (XP2AS) at
      Asahikawa Medical College, and five patients, namely, a 53 years old male
      (XP1SA), a 45 years old female (XP2SA), a 46 years old female (XP3SA), a 47 years
      old male (XP4SA) and a 34 years old male (XP5SA) at Hokkaido University School of
      Medicine. All these XP patients showed mild skin symptoms and had no apparent
      neurological abnormalities. To identify genetic complementation groups of these
      patients, DNA repair capacities in skin fibroblasts derived from the patients
      were analyzed by ultraviolet light (UV)-induced unscheduled DNA synthesis (UDS),
      and also by colony-forming abilities of UV-irradiated cells incubated with or
      without caffeine added in post-UV culture medium. The levels of UDS measured by
      autoradiography in these XP cells irradiated with 20 J/m2 of UV were 67 to 84% of
      those of normal human fibroblasts. Although one XP cell strain (XP2AS) showed
      about 2-fold greater sensitivity to killing by UV than normal cells, UV
      sensitivities of the rest of 5 XP strains were similar or only slightly higher
      than those of normal cells. However, UV sensitivities of all the 6 XP cell
      strains markedly increased by addition of 1 mM caffeine in the post-UV incubation
      medium, a phenomenon characteristic of XP variant cells. We also analyzed post
      replication repair in XP1SA cells by sedimentation of newly-synthesized DNA in
      alkaline sucrose gradient, and found that this strain is defective in this repair
      system. From these results, we concluded that all the 6 XP strains studied here
      belong to XP variants.

PMID- 7830261
TI  - Genetic control of the radiosensitivity of lymphoid cells for antibody formation
      ability in mice.
AB  - To analyze the genetic basis of the relationship between the radiosensitivity of
      the immune response and radiation lymphomagenesis, we examined the
      radiosensitivity of lymphoid cells for antibody formation in BALB/cHeA, STS/A, F1
      hybrids, and their recombinant inbred mouse strains. The decrease in the number
      of plaque-forming spleen cells in BALB/cHeA mice exposed to 3 Gy X-irradiation
      was more than tenfold that in STS/A mice. The phenotype of radioresistance was
      dominant over sensitivity. The coincidence between the strain distribution
      patterns of the genetic markers and radiosensitivities of antibody formation in
      the various recombinant inbred strains was in the region with the Igh locus on
      chromosome 12. There was obvious difference between the patterns in the region
      containing the Ifa locus on chromosome 4 which has been shown to be related to
      the incidence of radiation-induced lymphomas. These results indicate that the
      region on chromosome 12 may contain major gene(s) related to radiosensitivity for
      antibody formation.

PMID- 7830262
TI  - Validation of screening immobilized peptide libraries for discovery of protease
      substrates.

PMID- 7830263
TI  - Aspartyl alpha-((diphenylphosphinyl)oxy)methyl ketones as novel inhibitors of
      interleukin-1 beta converting enzyme. Utility of the diphenylphosphinic acid
      leaving group for the inhibition of cysteine proteases.

PMID- 7830264
TI  - Inhibition of human neutrophil elastase. 3. An orally active enol acetate
      prodrug.
AB  - Several analogs of N-[4-(4-morpholinylcarbonyl)benzoyl]-L-valyl-N-[3,3,4,4,4
      penta fluoro-1- (1-methylethyl)-2-oxobutyl]-L-prolinamide (1), in which the
      chiral center of the P1 residue has been eliminated, were synthesized and tested
      as inhibitors of human neutrophil elastase (HNE). Observations made during the
      course of this work led to the development of a single-step, stereoselective
      synthesis of E-enol acetate derivatives from HNE inhibitors containing a mixture
      of epimers at P1. In vitro studies, in the presence of added esterase, and 19F
      NMR studies, in biological media, indicated that the E-enol acetate derivatives
      should act as prodrugs in vivo. The ED50 value for (E)-N-[4-(4
      morpholinylcarbonyl)benzoyl]-L-valyl-N-[2- (acetyloxy)-3,3,4,4,4-pentafluoro-1-(1
      methylethyl)-1-buteny l]-L-prolinamide (20), when administered orally in the
      hamster lung hemorrhage model, was 9 mg/kg.

PMID- 7830265
TI  - Antitumor activity of 5-aryl-2,3-dihydroimidazo[2,1-a]isoquinolines.
AB  - A series of 5-aryl-2,3-dihydroimidazo[2,1-a]isoquinolines previously reported to
      be platelet activating factor (PAF) receptor antagonists were evaluated for
      potential antitumor activity. Several compounds, such as the 5-(4'-tert
      butylphenyl) (65), 5-[4'-(trimethylsilyl)phenyl] (69), and 5-(4'
      cyclohexylphenyl) (71) analogs showed very good cytotoxicity against several
      tumor cell lines. 5-[4'-(Piperidinomethyl)phenyl]-2,3-dihydroimidazo[2,1-
      a]isoquinoline (SDZ 62-434, 53) was more effective on a milligram per kilogram
      basis than the clinical cytostatic agent edelfosine (1) in increasing survivors
      and decreasing tumor volume in the oral mouse Meth A fibrosarcoma assay. It was
      selected for further development and is currently in phase I clinical trials in
      cancer patients.

PMID- 7830266
TI  - Rationally designed analogues of tamoxifen with improved calmodulin antagonism.
AB  - Computerized molecular modeling studies on the interactions of the antiestrogen
      tamoxifen (1) and its analogues bound to the calcium-binding protein calmodulin
      have guided the rational design of more potent antagonists. Compounds with either
      three or four methylene units in the basic side chain or slim lipophilic 4
      substituents were expected to be more potent. All compounds were tested for
      antagonism of the calmodulin-dependent activity of cAMP phosphodiesterase and for
      binding affinity to the estrogen receptor from rat uteri. Some compounds were
      assayed for cytotoxicity against MCF-7 breast tumor cells in vitro. Introduction
      of lipophilic 4-substituents was accomplished by using palladium(0)-catalyzed
      coupling reactions with a 4-iodinated precursor. Both the 4-ethynyl (16 and 17)
      and 4-butyl (18 and 19) compounds were more potent calmodulin antagonists than
      tamoxifen. Extension of the basic aminoethoxy side chain of 4-iodotamoxifen (3)
      and idoxifene (2) ((E)-1-[4-[2-(N-pyrrolidino)ethoxy]phenyl]-1-(4-iodophenyl)-2
      phen yl-1- butene) by one or two methylene units resulted in modest gains in
      calmodulin antagonism (10-13). All the compounds assayed retained estrogen
      receptor binding characteristics. The compound possessing the optimal combination
      of calmodulin antagonism and estrogen receptor binding was 12 ((E)-1-[4-[3-(N
      pyrrolidino)propoxy]phenyl]-1-(4-iodophenyl)-2-phe nyl-1 - butene) (IC50 = 1.1
      microM, RBA = 23). Correlation between calmodulin antagonism and cytotoxicity was
      demonstrated for selected compounds.

PMID- 7830267
TI  - Design and structure-activity relationships of C-terminal cyclic neurotensin
      fragment analogues.
AB  - Neurotensin (NT) is a linear tridecapeptide with a broad range of central and
      peripheral pharmacological effects. The C-terminal hexapeptide of NT (NT8-13) has
      been shown to possess similar properties to NT itself, and in fact, an analogue
      of NT8-13 (N alpha MeArg8-Lys-Pro-Trp-Tle-Leu13, Tle = tert-leucine) has been
      reported to possess central activity after peripheral administration. Cyclic
      derivatives of this hexapeptide were synthesized by a combination of solution and
      solid-phase peptide synthetic methodologies, and several analogues had low
      nanomolar binding affinity for the NT receptor. In particular, cyclo[Arg-Lys-Pro
      Trp-Glu]-Leu (cyclized between the alpha amine of Arg and the gamma carboxylate
      of Glu) possessed 16 nM NT receptor affinity and was determined to be an agonist
      in vitro. 1H-NMR and 13C-edited 1H-NMR spectroscopy were performed on this and
      related cyclic analogues to help identify structural properties which may be
      important for receptor recognition. These cyclic peptides represent novel
      molecular probes to further investigate NT receptor pharmacology, as well as to
      advance our understanding of the structure-conformation relationships of NT and
      to help establish a working basis for additional pharmacophore mapping studies.

PMID- 7830268
TI  - 5-(Diethoxyphosphoryl)-5-methyl-1-pyrroline N-oxide: a new efficient
      phosphorylated nitrone for the in vitro and in vivo spin trapping of oxygen
      centered radicals.
AB  - 5-(Diethoxyphosphoryl)-5-methyl-1-pyrroline N-oxide (DEPMPO, 2), a new spin trap,
      has been synthesized via a two-step synthetic route, and its ability to spin trap
      oxy radicals in biological milieu has been addressed. The in vitro spin trapping
      of hydroxyl and superoxide radicals was investigated in a phosphate buffer 0.1 M,
      and the hyperfine coupling constants of the spin adducts were determined. The
      rates of spin trapping of hydroxyl and superoxide radicals with 2 were found to
      be close to those reported for 5,5-dimethyl-1-pyrroline N-oxide (DMPO). However,
      the DEPMPO-superoxide spin adduct was shown to be significantly more persistent
      (15 times at pH 7) than the DMPO--superoxide spin adduct. Using 2 as a spin trap,
      the production of superoxide has been clearly characterized during the
      reperfusion of ischemic isolated rat hearts.

PMID- 7830269
TI  - Homologs of histamine as histamine H3 receptor antagonists: a new potent and
      selective H3 antagonist, 4(5)-(5-aminopentyl)-1H-imidazole.
AB  - The influence of alkyl chain length variation on the histamine H3 receptor
      activity of histamine homologs 1 was investigated. A series of 4(5)-(omega
      aminoalkyl)-1H-imidazoles 1 was prepared with an alkyl chain length varying from
      one methylene group to 10 methylene groups. Besides the H3 activity, the
      affinities of these compounds for the H1 and H2 receptors were determined. The
      ethylene chain of histamine is optimal for agonistic activity on all three
      histamine receptor subtypes. For the H3 receptor, elongation of the alkyl chain
      from three methylene groups on leads to compounds with antagonistic properties.
      4(5)-(5-Aminopentyl)-1H-imidazole (impentamine, 1e) is the most potent and
      selective H3 antagonist from this series of 4(5)-(omega-aminoalkyl)-1H-imidazoles
      1, with a pA2 value of 8.4 (on guinea pig jejunum). A specific antagonistic
      binding site for this compound is proposed.

PMID- 7830270
TI  - Structure-activity relationships of analogues of thapsigargin modified at O-11
      and O-12.
AB  - A number of analogues of thapsigargin have been synthesized by alkylating or
      acylating O-11 and O-12 in the lactol obtained by reducing thapsigargicin.
      Introduction of alpha-disposed substituents decreased the Ca(2+)-ATPase
      inhibitory potency of the analogue, whereas the enzyme was more tolerant toward
      beta-disposed substituents, indicating that the alpha-face of the lactone ring is
      in close contact with the binding site when the inhibitor is bound to the enzyme.

PMID- 7830271
TI  - Synthesis and biological evaluation of a new series of sterols as potential
      hypocholesterolemic agents.
AB  - A new series of sterols was synthesized and tested in a CHO cell-based LDL
      receptor/luciferase (LDLR/Luc) assay to investigate the capability of
      derepressing the transcription of LDL receptor promoter in the presence of 25
      hydroxycholesterol. The effect of various substitutions on antagonizing the
      repressing effect mediated by 25-hydroxycholesterol was also studied in terms of
      regio- and stereochemistry, lipophilicity, steric bulk, and pi-electron density.
      Except 12, compounds active in the primary LDLR/Luc assay were not active in the
      secondary simian virus 40/luciferase (SV40/Luc) assay, demonstrating the
      specificity of their in vitro activity. Eight active compounds of various
      structural types were selected and screened in a [1-14C-acetate]cholesterol
      biosynthesis inhibition assay; none has shown any interference with the
      cholesterol biosynthesis in CHO cells. In hypercholesterolemic hamsters,
      generally, compounds that were active in vitro were active in vivo and vice
      versa, with the exception of three in vitro inactive compounds: 3 beta-ols 3a'
      and 3c' as well as 3-ketone 2a. Experimental results from the livers of hamsters
      revealed that the in vivo conversion of 3a' or 2a to 3a has in part contributed
      to the observed in vivo activity, and it is also anticipated that 3c' may
      similarly be converted to 3c in hamsters.

PMID- 7830272
TI  - Derivatives of 17-phenyl-18,19,20-trinorprostaglandin F2 alpha isopropyl ester:
      potential antiglaucoma agents.
AB  - The 15R and 15S epimers of a series of phenyl substituted analogs of 17-phenyl
      18,19,20-trinorprostaglandin F2 alpha isopropyl ester [(15S)-3] have been
      synthesized. The intraocular pressure (IOP) lowering effects and potential side
      effects of these novel derivatives have been studied in cats and rabbits. In
      addition, the effects of selected analogues on IOP have been studied in monkeys.
      Furthermore, we have hydrolyzed some of the isopropyl esters and assessed the
      ability of the resulting carboxylic acids to contract the cat iris sphincter
      muscle in vitro. In general, the 15S-derivatives were more active than the 15R
      epimers. Derivatives substituted with an acetyl group in the benzene ring
      appeared to have a better side effect profile as compared to (15S)-3.
      Furthermore, substitution with an aromatic moiety had a dramatic effect on the
      activity in that the resulting compounds reduced IOP in cats but had little
      effect on the pupil diameter. Thus, the activity profile of (15S)-3 may be
      changed by the introduction of substituents in the benzene ring.

PMID- 7830273
TI  - A priori prediction of activity for HIV-1 protease inhibitors employing energy
      minimization in the active site.
AB  - We have observed a high correlation between the intermolecular interaction energy
      (Einter) calculated for HIV-1 protease inhibitor complexes and the observed in
      vitro enzyme inhibition. A training set of 33 inhibitors containing modifications
      in the P1' and P2' positions was used to develop a regression equation which
      relates Einter and pIC50. This correlation was subsequently employed to
      successfully predict the activity of proposed HIV-1 protease inhibitors in
      advance of synthesis in a structure-based design program. This included a
      precursor, 47, to the current phase II clinical candidate, L-735,524 (51). The
      development of the correlation, its applications, and its limitations are
      discussed, and the force field (MM2X) and host molecular mechanics program
      (OPTIMOL) used in this work are described.

PMID- 7830274
TI  - Evaluation of cis- and trans-9- and 11-hydroxy-5,6,6a,7,8,12b
      hexahydrobenzo[a]phenanthridines as structurally rigid, selective D1 dopamine
      receptor ligands.
AB  - The present study reports the investigation of the D1 structure-relationships of
      certain cis- or trans-9- or 11-monohydroxy analogues of (+/-)-trans-10,11
      dihydroxy-5,6,6a,7,8,12b-hexahydrobenzo[a] phenanthridine (8a, dihydrexidine),
      previously identified as the first full efficacy D1 dopamine receptor agonist.
      The monohydroxybenzo[a]phenanthridines were prepared from the appropriately
      substituted beta-tetralones using the methods described earlier for the synthesis
      of their catechol analogues. The 10-bromo 11-hydroxy derivative 9e was prepared
      by treatment of precursor 9c with bromine in chloroform. The affinities of these
      compounds for the D1 and D2 dopamine receptor classes and for their effects on
      adenylate cyclase activity were assessed in rat striatal membranes. In addition
      to producing only minimal increases in adenylate cyclase activity (< or = 15%),
      these phenolic derivatives generally had significantly lower affinities for D1
      and D2 receptors (D1 IC50 > or = 102 nM, D2 IC50 > or = 210 nM) than did their
      catechol analogues. Further, compounds bearing a cis B/C-ring fusion displayed
      lower affinities than those bearing a trans configuration, paralleling the
      activity differences between the catechol analogues. The data for these rigid
      dopamine receptor ligands from the benzo[a]phenanthridine class lend additional
      support for the hypothesis that D1 agonist activity is optimized by a trans ring
      configuration that maintains the beta-phenyldopamine substructure in the "trans
      beta-rotamer."

PMID- 7830275
TI  - Fluorine-18-labeled progestin 16 alpha, 17 alpha-dioxolanes: development of high
      affinity ligands for the progesterone receptor with high in vivo target site
      selectivity.
AB  - We describe the synthesis and tissue biodistribution of two 21-[fluoro
      18F]progestin 16 alpha, 17 alpha-furanyl ketals, potential agents for imaging
      progesterone receptor (PR)-positive breast tumors in humans, using positron
      emission tomography. 21-Fluro-16 alpha, 17 alpha-[(R)-(1'-alpha
      furylmethylidene)dioxy]-19- norpregn-4-ene-3,20-dione (endo-10a) and 21-fluoro-16
      alpha, 17 alpha-[(R)-(1'-alpha-furylethylidene)dioxy]-19- norpregn-4-ene-3,20
      dione (endo-10b) were chosen for radiochemical synthesis from a series of seven
      novel progestin 16 alpha, 17 alpha-(furanyldioxolanes) on the basis of their high
      relative binding affinity to PR (190% and 173%, respectively, relative to R5020 =
      100%), their low nonspecific binding (NSB) (log P o/w = 3.87 and 4.13,
      respectively), and their resulting high binding selectivity indices (BSI; i.e.,
      the ratio of their PR binding affinity to nonspecific binding). Radiochemical
      synthesis of these two species in high radiochemical purity and at high effective
      specific activity was accomplished by treatment of the corresponding
      diastereomerically pure 21-trifluoromethanesulfonates with fluorine-18 anion. In
      tissue biodistribution studies in estrogen-primed immature female Sprague-Dawley
      rats, both [18F]-endo-10a and [18F]endo-10b demonstrated high PR-selective uptake
      in the principal target tissues, the uterus and the ovaries, and relatively low
      uptake in fat and bone. The metabolism at the 21-position in these progestins (as
      monitored by in vivo defluorination) appears to be less than that in other 21
      fluoroprogestins; this may reflect steric inhibition of metabolism at this site
      due to the bulk of the furan-substituted dioxolane ring at the 16 alpha, 17 alpha
      position. Comparison with other fluorine-18-labeled progestins shows that the PR
      specific uptake in uterine tissue correlates with the BSI of the ligand and that
      the fat uptake correlates with the NSB of the ligand at high levels of
      statistical significance. These two dioxolanes may prove to be useful as breast
      tumor-imaging agents in humans.

PMID- 7830276
TI  - Halicylindramides A-C, antifungal and cytotoxic depsipeptides from the marine
      sponge Halichondria cylindrata.
AB  - Halicylindramides A-C (1-3) have been isolated from the Japanese marine sponge
      Halichondria cylindrata. They are tetradecapeptides with the N-terminus blocked
      by a formyl group and the C-terminus lactonized with a threonine residue. Their
      total structures including absolute stereochemistry were determined by a
      combination of spectral and chemical methods. Halicylindramides A-C were
      antifungal against Mortierella ramanniana and cytotoxic against P388 murine
      leukemia cells.

PMID- 7830277
TI  - Deconvolution of combinatorial libraries for drug discovery: a model system.
AB  - Iterative synthesis and screening strategies have recently been used to identify
      unique active molecules from complex synthetic combinatorial libraries. These
      techniques have many advantages over traditional screening methods, including the
      potential to screen large numbers of compounds to identify an active molecule
      while avoiding analytical separations and structural determination of unknown
      compounds. It is not clear, however, whether these techniques identify the most
      active molecular species in the mixtures and, if so, how often. Two key factors
      which may affect success of the selection process are the presence of many active
      compounds in the library with a range of activities and the chosen order of
      unrandomization. The importance of these factors has not been previously studied.
      Moreover, the impact of experimental errors in determination of subset activities
      or in randomization during library synthesis is not known. We describe here a
      model system based on oligonucleotide hybridization that addresses these
      questions using computer simulations. The results suggested that, within
      achievable experimental and library synthesis error, iterative deconvolution
      methods generally find either the best molecule or one with activity very close
      to the best. The presence of many active compounds in a library influenced the
      profile of subset activities, but did not preclude selection of a molecule with
      near optimal activity.

PMID- 7830278
TI  - Novel thiazole derivatives as inhibitors of superoxide production by human
      neutrophils: synthesis and structure-activity relationships.
AB  - Neutrophils have an important role in the self-defense systems of organisms
      through the production of superoxide. On the other hand, it has been proposed
      that abnormal amounts of superoxide produced by neutrophils are a serious factor
      in tissue injury. A series of novel thiazole derivatives was prepared and
      evaluated inhibitory effect on superoxide production by human neutrophils in
      vitro. Among these compounds, 6-[2-(3,4-diethoxyphenyl)thiazol-4-yl]-pyridine-2
      carboxylic acid (OPC-6535) was selected as one of the most promising compounds.
      The synthesis and structure-activity relationships of these compounds are
      reported herein.

PMID- 7830279
TI  - 8-Substituted O6-benzylguanine, substituted 6(4)-(benzyloxy)pyrimidine, and
      related derivatives as inactivators of human O6-alkylguanine-DNA
      alkyltransferase.
AB  - Several 8-substituted O6-benzylguanines, 2- and/or 8-substituted 6
      (benzyloxy)purines, substituted 6(4)-(benzyloxy)pyrimidines, and a 6-(benzyloxy)
      s-triazine were tested for their ability to inactivate the human DNA repair
      protein, O6-alkylguanine-DNA alkyltransferase (AGT, alkyltransferase). Two types
      of compounds were identified as being significantly more effective than O6
      benzylguanine (the prototype low molecular weight inactivator) at inactivating
      AGT in human HT29 colon tumor cell extracts. These were 8-substituted O6
      benzylguanines bearing electron-withdrawing groups at the 8-position (e.g. 8-aza
      O6-benzylguanine and O6-benzyl-8-bromoguanine) and 5-substituted 2,4-diamino-6
      (benzyloxy)pyrimidines bearing electron-withdrawing groups at the 5-position
      (e.g. 2,4-diamino-6-(benzyloxy)-5-nitroso- and 2,4-diamino-6-(benzyloxy)-5
      nitropyrimidine). The latter derivatives were also more effective than O6
      benzylguanine at inactivating AGT in intact HT29 colon tumor cells. Provided
      these types of purines and pyrimidines do not exhibit undesirable toxicity, they
      may be superior to O6-benzylguanine as chemotherapeutic adjuvants for enhancing
      the effectiveness of antitumor drugs for which the mechanism of action involves
      modification of the O6-position of DNA guanine residues.

PMID- 7830280
TI  - Synthesis and structure-activity relationships of phenylenebis(methylene)-linked
      bis-tetraazamacrocycles that inhibit HIV replication. Effects of macrocyclic ring
      size and substituents on the aromatic linker.
AB  - We have previously described the potent and selective inhibition of several
      strains of human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) by
      JM2763, an n-propyl-linked dimer of the 1,4,8,11-tetraazamacrocyclic (cyclam)
      ring system. Upon further investigation, we have also found that incorporating an
      aromatic rather than aliphatic linker leads to analogs with higher antiviral
      potency. The prototype, JM3100 (19a, isolated as the octahydrochloride salt),
      which contains a p-phenylenebis(methylene) moiety linking the cyclam rings,
      inhibited the replication of HIV-1 (IIIB) and HIV-2 (ROD) at EC50's of 4.2 and
      5.9 nM, respectively, while remaining nontoxic to MT-4 cells at concentrations
      exceeding 421 microM. In order to identify the structural features of bis
      tetraazamacrocycles required for potent activity, we have prepared a novel series
      of phenylenebis(methylene)-linked analogs, in which the macrocyclic ring size was
      varied from 12 to 16 ring members. Depending upon the substitution of the
      phenylenebis(methylene) linker (para or meta), sub-micromolar anti-HIV activity
      was exhibited by analogs bearing macrocycles of 12-14 ring members but with
      varying cytotoxicity to MT-4 cells. Furthermore, while we found that identical
      macrocyclic rings are not required for activity, substituting an acyclic
      polyamine equivalent for one of the cyclam rings in 19a resulted in a substantial
      reduction in anti-HIV potency, clearly establishing the importance of the
      constrained macrocyclic structure. A short series of transition metal complexes
      of 19a were also prepared and evaluated. Complexes of low kinetic stability such
      as the bis-zinc complex retained activity comparable to that of the parent
      compound. Finally, the activity of bicyclam analogs appears to be insensitive to
      the electron-withdrawing or -donating properties of substituents introduced onto
      the linker, but sterically hindering groups such as phenyl markedly reduced
      activity. As a result, several analogs with anti-HIV potency comparable to that
      of 19a have been identified.

PMID- 7830281
TI  - Cocaine and 3 beta-(4'-substituted phenyl)tropane-2 beta-carboxylic acid ester
      and amide analogues. New high-affinity and selective compounds for the dopamine
      transporter.
AB  - Several 2 beta-carboxylic acid ester and amide analogues of cocaine and of 3 beta
      (4'-substituted phenyl)tropane-2 beta-carboxylic acid were prepared. The binding
      affinities of these compounds, and of some previously prepared analogues, at the
      dopamine (DA), norepinephrine (NE), and serotonin (5-HT) transporters were
      determined. The phenyl esters of 3 beta-(4'-methylphenyl)- and 3 beta-(4'
      chlorophenyl)tropane-2 beta-carboxylic acid are highly potent and highly
      selective for the DA transporter. The isopropyl esters of 3 beta-(4'
      chlorophenyl)- and 3 beta-(4'-iodophenyl)tropane-2 beta-carboxylic acid also
      possess high DA affinity and show significant DA transporter selectivity.
      Similarly, the phenyl and isopropyl ester analogues of cocaine are much more
      selective for the DA transporter than cocaine. Tertiary amide analogues of
      cocaine and of 3 beta-(4'-substituted phenyl)tropane-2 beta-carboxylic acids are
      more potent inhibitors of radioligand binding at the DA transporter than the
      primary and secondary amide analogues. In particular, 3 beta-(4'
      chlorophenyl)tropane-2 beta-N-morpholinocarboxamide as well as the 3 beta-(4'
      chlorophenyl)- and 3 beta-(4'-iodophenyl)tropane-2 beta-N-
      pyrrolidinocarboxamides possess high affinity and selectivity for the DA
      transporter. The N,N-dimethylamide cocaine analogue is the most selective cocaine
      amide derivative for the DA transporter. High correlation between the inhibition
      of radioligand binding and inhibition of uptake at the DA, NE, and 5-HT
      transporter was found for a selected group of analogues. Within this group, one
      compound, the isopropyl ester of 3 beta-(4'-iodophenyl)-tropane-2 beta-carboxylic
      acid, was found to be more potent in the inhibition of radioligand binding than
      in the inhibition of DA uptake. Taken together with its high potency and
      selectivity at the DA transporter, this suggests that this compound may be a lead
      in the development of a cocaine antagonist.

PMID- 7830282
TI  - Specific inhibition of poly(ADP-ribose) glycohydrolase by adenosine diphosphate
      (hydroxymethyl)pyrrolidinediol.
AB  - Adenosine diphosphate (hydroxymethyl)pyrrolidinediol (ADP-HPD), an NH analog of
      ADP-ribose, was chemically synthesized and shown to be a potent and specific
      inhibitor of poly-(ADP-ribose) glycohydrolase. The synthetic starting material
      was the protected pyrrolidine, (2R,3R,4S)-1-(benzyloxycarbonyl)-2
      (hydroxymethyl)pyrrolidine-3,4-diol 3,4-O-isopropylidene acetal. This starting
      pyrrolidine was phosphorylated, coupled to adenosine 5'-monophosphate, and
      deprotected, yielding the title inhibitor ADP-HPD. ADP-HDP was shown to inhibit
      the activity of poly(ADP-ribose) glycohydrolase by 50% (IC50) at 0.12 microM, a
      value 1000-times lower than the IC50 of the product, ADP-ribose. The NAD
      glycohydrolase from Bungarus fasciatus venom was less sensitive to inhibition by
      ADP-HPD, exhibiting an IC50 of 260 microM. ADP-HPD did not inhibit either
      poly(ADP-ribose) polymerase or NAD:arginine mono(ADP-ribosyl)-transferase A at
      inhibitor concentrations up to 1 mM. At low ADP-HPD concentration, inhibition was
      therefore shown to be highly specific for poly(ADP-ribose) glycohydrolase, the
      hydrolytic enzyme in the metabolism of ADP-ribose polymers.

PMID- 7830283
TI  - Influence of propagermanium (SK-818) on chemically induced renal lesions in rats.
AB  - A histopathological study was performed to examine the influence of
      propagermanium and germanium dioxide (GeO2) on chemically induced renal lesions
      in rats. Animals were treated with adriamycin or mercuric chloride to induce
      glomerular or proximal tubular damage, and then given drinking water containing
      propagermanium (480 or 2,400 ppm solution) or GeO2 (300 or 1,500 ppm solution:
      equivalent to propagermanium in terms of germanium contents). The distal tubular
      epithelium after 8 weeks dosage with the 1,500 ppm solution of GeO2 was
      characterized by vacuolization and deposits of PAS-positive material not only in
      adriamycin-treated rats, but also in normal rats. In contrast, propagermanium
      administration was not associated with any alternation in the changes induced by
      adriamycin or mercuric chloride. We previously clarified that propagermanium had
      no biochemical influence on the renal function of these renal injured rats. The
      histological demonstration that this compound does not exert renal toxicity, even
      when given at a high dosage to renal injured rats, further indicates that it
      would not exacerbate renal dysfunction already present. This confirms that
      propagermanium may be a safe compound for use in individuals with compromised
      kidneys.

PMID- 7830284
TI  - [Single-dose toxicity studies of tazobactam/piperacillin and tazobactam].
AB  - Tazobactam (TAZ) is a newly developed beta-lactamase inhibitor.
      Tazobactam/Piperacillin (TAZ/PIPC) is a formulation consisting of TAZ and PIPC in
      a ratio of 1:4. Singe-dose toxicity studies in TAZ/PIPC and TAZ were carried out
      using mice and rats of both sexes and male dogs. The results were as follows. 1.
      A common clinical sign in mice and rats administered TAZ/PIPC or TAZ by all
      routes was soft stool. Other signs in mice and rats included a decrease in
      spontaneous motor activity and/or a decreased respiratory rate for the
      intraperitoneal (i.p.), subcutaneous (s.c.) or intravenous (i.v.) route. The
      animals administered by the i.v. route showed tremor for mice and clonic
      convulsion for rats before death. Hyperemia, hemorrhage or edema of the lung, and
      hemorrhage of the digestive tract were observed in these animals at necropsy. An
      enlargement of the spleen was seen in some of the surviving animals treated with
      TAZ/PIPC. 2. In dogs, TAZ/PIPC caused vomiting, and TAZ caused vomiting,
      respiratory abnormality, soft stool and diarrhea by the intravenous (i.v.)
      administration. 3. TAZ/PIPC or TAZ caused clinical signs such as the loss of hair
      at the injection site for the s.c. route, and necrosis of the tail for the i.v.
      route in mice and rats, also caused limping of the injected anterior limb in
      dogs. Necrosis and hemorrhage at the injection site, and peritonitis by the i.p.
      injection were observed at necropsy. These findings were due to the irritation of
      TAZ/PIPC or TAZ.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7830285
TI  - [A six-month intraperitoneal repeated dose toxicity study of
      tazobactam/piperacillin and tazobactam in rats].
AB  - Tazobactam (TAZ) is a newly developed beta-lactamase inhibitor.
      Tazobactam/Piperacillin (TAZ/PIPC) is a formulation consisting of TAZ and PIPC in
      a ratio of 1:4. A six-month intraperitoneal repeated dose toxicity study of
      TAZ/PIPC and TAZ including a one-month recovery period were carried out using
      male and female rats. The doses were 200, 400 and 800 mg/kg/day for TAZ/PIPC, and
      40, 80 and 160 mg/kg/day for TAZ. The results were as follows. 1. No test article
      related deaths occurred during the study period. No effect on clinical finding of
      survival rats was evident. 2. There was no dose-related increases of food
      consumption in both the males and females given TAZ/PIPC and PIPC. Slight
      reductions in body weight gain occurred in males given 800 mg/kg/day of TAZ/PIPC.
      3. Decreases in erythrocyte, hemoglobin and hematocrit, and increases in
      reticulocytes were seen only at study termination in the group given 800
      mg/kg/day of TAZ/PIPC. Increases in reticulocytes were seen only at study
      termination in the females given 80 or 160 mg/kg/day of TAZ. 4. A decrease in
      triglyceride levels was observed in the males given 800 mg/kg/day of TAZ/PIPC or
      160 mg/kg/day of TAZ. 5. The ophthalmoscopic examination or urinalysis show no
      test article-related changes. 6. Enlarged ceca in all groups of animals given
      TAZ/PIPC and in the females given 160 mg/kg/day of TAZ were observed. 7. An
      increase of relative organ weight in liver was noted in the males and females
      given 800 mg/kg/day of TAZ/PIPC, in the males given 80 or 160 mg/kg/day of TAZ
      and in the females given 160 mg/kg/day of TAZ. 8. In the hepatocytes,
      accumulation of PAS-positive materials which was identified histochemically and
      ultrastructurally as glycogen, was present in the males given 800 mg/kg/day of
      TAZ/PIPC and in the males given 80 or 160 mg/kg/day of TAZ. 9. After a one-month
      recovery period, the changes of liver had generally disappeared, suggesting that
      they were reversible. 10. From the histopathological changes of liver, the no
      toxic dose level in both the males and females was 400 mg/kg/day and 40 mg/kg/day
      for TAZ/PIPC and TAZ, respectively.

PMID- 7830286
TI  - [A six-month intravenous repeated dose toxicity study of tazobactam/piperacillin
      and tazobactam in dogs].
AB  - Tazobactam (TAZ) is a newly developed beta-lactamase inhibitor.
      Tazobactam/Piperacillin (TAZ/PIPC) is a formulation consisting of TAZ and PIPC in
      a ratio of 1:4. A six-month intravenous repeated dose toxicity study of TAZ/PIPC
      and TAZ including a one-month recovery period were carried out using male and
      female dogs. The doses were 200, 400 and 800 mg/kg/day for TAZ/PIPC, and 40, 80
      and 160 mg/kg/day for TAZ. The results were as follows. 1. No test article
      related deaths occurred during the study period. No effects on clinical findings,
      body weight and food consumption were evident. 2. No test article-related changes
      were noted in hematological, serum biochemical and urinalysis evaluations, and
      opthalmological and electrocardiographic examinations. 3. There were no test
      article-related changes in macroscopic findings or organ weight. 4. The
      histopathological examination revealed deposition of marked PAS-positive
      aggregates in liver cells of dogs given 400 mg/kg/day or more of TAZ/PIPC and 80
      mg/kg/day or more of TAZ. Electron micrographs of hepatocytes revealed glycogen
      granules to be accumulated in the cytoplasm, and an increase of smooth
      endoplasmic reticulum. 5. After a one-month recovery period, the
      histopathological changes had generally disappeared, suggesting that they were
      reversible. 6. From the histopathological changes of liver, the no-toxic dose
      levels for TAZ/PIPC and TAZ were 200 mg/kg/day and 40 mg/kg/day, respectively.

PMID- 7830287
TI  - [Reproductive and developmental toxicity studies of tazobactam/piperacillin or
      tazobactam(1)--Fertility and general reproduction study in rats with
      intraperitoneal administration].
AB  - Tazobactam (TAZ) is a newly developed beta-lactamase inhibitor and piperacillin
      (PIPC) is an antibiotics which is used in clinical field widely. The combination
      of TAZ and PIPC (TAZ/PIPC), which is combined with TAZ and PIPC at rate of 1:4,
      has been developed because of PIPC is unstable to various beta-lactamases.
      Fertility and general reproductive performance were studied in rats given daily
      intraperitoneal doses of TAZ/PIPC (200, 800 or 1600 mg/kg/day) or TAZ (40, 160 or
      640 mg/kg/day). TAZ/PIPC or TAZ were given during premating period (70 days in
      males and 15 days in females), the pairing period (in males and females) and the
      gestation and lactation periods (in females). Total daily doses were administered
      in two equally divided doses. The study includes evaluation of the F1 generation
      and the F2 generation through weaning. In the TAZ/PIPC, maternal toxicity
      (decreased food consumption) was observed at 200 mg/kg and above dosage groups.
      At maternotoxic doses of 800 and 1600 mg/kg groups, increased resorptions,
      decreased live litter size, and increased fetal variations (reversible changes in
      ribs) were observed. Reversible delays in ossification of caudal vertebrae were
      also observed at 1600 mg/kg group. In the TAZ, maternal toxicities were observed
      at 160 mg/kg group (decreased food consumption) and 640 mg/kg group (decreased
      body weight gain and food consumption). Furthermore, necropsy (raised and/or
      colored areas present in the cecum) revealed slight increases at 40 mg/kg and
      above dosage groups. Slight decreases in implantations and resultant slight
      decreases in live litter size, reversible delays in renal development, and
      increased stillbirths were observed at 640 mg/kg group. Postnatal growth and
      development, behavior and reproductive performance of the F1 generation were not
      affected by the administration of TAZ/PIPC or TAZ. There were no effects on any
      of the fetal or pup parameters evaluated in the F2 generation. In conclusion,
      mating behavior and fertility were not affected by TAZ/PIPC or TAZ in this study.
      TAZ/PIPC or TAZ caused adverse change in reproductive performance of the F0
      generation only at doses that caused maternal toxicity. The F1 and F2 generation
      were not affected.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7830288
TI  - [Reproductive and developmental toxicity studies of tazobactam/piperacillin or
      tazobactam (2)--Teratological study in rats with intravenously administration].
AB  - Tazobactam (TAZ) is a newly developed beta-lactamase inhibitor and piperacillin
      (PIPC) is an antibiotics which is used in clinical field widely. The combination
      of TAZ and PIPC (TAZ/PIPC), which is combined with TAZ and PIPC at rate of 1:4,
      has been developed because of PIPC is unstable to various beta-lactamases.
      Teratogenic potential were studied in rats given daily intravenous doses of
      TAZ/PIPC (625, 1250, 2500 or 3750 mg/kg/day) or TAZ (125, 500 or 3000 mg/kg/day).
      TAZ/PIPC or TAZ were given from day 7 to day 17 of pregnancy. Total daily doses
      were administered in two equally divided doses. The study includes postnatal
      evaluation of the growth and development and reproductive performance of the F1
      generation. Maternal deaths occurred in all groups given TAZ/PIPC. The incidence
      (range of 3 to 6 animals/group) was not dose dependent. Maternal body weight was
      decreased in rats receiving 3000 mg/kg of TAZ and food consumption was reduced in
      all drug-treated groups. Slight decreases in fetal body weights were observed at
      some doses that caused maternal body-weight or food-consumption decreases (2500
      or 3750 mg/kg of TAZ/PIPC, 3000 mg/kg of TAZ). But these depressions of fetal
      body weights were not significant from control data. There were no fetal
      malformations or variations attributable to the test articles. Postnatal growth
      and development, behavior and reproductive performance of the F1 generation were
      not affected by the administration of TAZ/PIPC or TAZ. In conclusion, TAZ/PIPC or
      TAZ was not teratogenic in the rats. It is seemed that non-observed effect dose
      levels (NOELs) of TAZ/PIPC and TAZ for dams is less than 625 and 125 mg/kg/day in
      general toxicity respectively, however, NOELs of TAZ/PIPC is 3750 mg/kg/day or
      more and that of TAZ is 300 mg/kg/day or more for their offspring under the
      condition of this study.

PMID- 7830289
TI  - [Reproductive and developmental toxicity studies of tazobactam/piperacillin or
      tazobactam (3)--Perinatal and postnatal study in rats with intraperitoneal
      administration].
AB  - Tazobactam (TAZ) is a newly developed beta-lactamase inhibitor and piperacillin
      (PIPC) is an antibiotics which is used in clinical field widely. The combination
      of TAZ and PIPC (TAZ/PIPC), which is combined with TAZ and PIPC at rate of 1:4,
      has been developed because of PIPC is unstable to various beta-lactamases.
      Perinatal and postnatal toxicity were studied in rats given daily intraperitoneal
      doses of TAZ/PIPC (200, 800 or 1600 mg/kg/day) or TAZ (40, 320 or 1280
      mg/kg/day). TAZ/PIPC or TAZ were given from day 17 of pregnancy through day 21 of
      lactation. Total daily doses were administered in two equally divided doses. In
      this study, evaluation of the late stage of gestation, parturition, lactation and
      maternal behavior in adult rats and postnatal evaluation of the growth and
      development, and reproductive performance of the F1 generation occurred. In the
      TAZ/PIPC, maternal toxicity (decreased food consumption) was observed at 800 and
      1600 mg/kg groups during perinatal period. A slight decrease in body weight gain
      during perinatal period and increased pup mortality and decreased pup weight in
      lactation period were observed at 1600 mg/kg group. An increase in stillbirths
      also was observed at 1600 mg/kg group. In the TAZ, maternal toxicity (decreased
      food consumption) was observed at all dosage groups during perinatal period. A
      decrease in body weight gain also were observed during perinatal period at 1280
      mg/kg group. At maternotoxic doses of 320 and 1280 mg/kg groups, decreased pup
      weight were observed during lactation period. An increase in stillbirths also was
      observed at 1280 mg/kg group. Transient, significant decrease in pup body weights
      at 1280 mg/kg group in early postweaning period. No other effects occurred for
      the F1 generation rats. In conclusion, perinatal development and postnatal growth
      and development of offspring were affected only at the intermediate and high
      doses that caused maternal toxicity in this study. Therefore it is seemed that
      non-observed effect dose levels (NOELs) of TAZ/PIPC for dams is less than 200
      mg/kg/day and that of TAZ is less than 40 mg/mg/day, and NOELs of TAZ/PIPC is 200
      mg/kg/day and that of TAZ is 40 mg/kg/day for offspring under the condition of
      this study.

PMID- 7830290
TI  - [Antigenicity tests of tazobactam/piperacillin, tazobactam and piperacillin].
AB  - The antigenicity tests of Tazobactam/piperacillin (TAZ/PIPC), tazobactam
      (TAZ:beta-lactamase inhibitor) and piperacillin (PIPC:penicillin antibiotic) were
      performed in mice and guinea pigs. The following results were obtained. 1.
      TAZ/PIPC, TAZ or PIPC had no immunogenicity and allergenicity in either passive
      cutaneous anaphylaxis (PCA) test using BALB/c and C3H/He mice or in PCA test
      using guinea pigs. 2. Guinea pigs sensitized with TAZ/PIPC, TAZ or PIPC showed no
      anaphylactic symptoms in active systemic anaphylaxis (ASA) test. 3. Guinea pig
      PCA tests using protein conjugates as sensitizing and challenging antigens showed
      positive reactions. Immunological cross-reactivity tests were performed by using
      these conjugates in guinea pig PCA reaction. Results showed that TAZ/PIPC and
      PIPC cross-reacted with penicillin G (PCG) and ampicillin (ABPC), but not with
      cephalothin (CET) and cephmetazol (CMZ). TAZ did not cross-react with PCG, ABPC,
      CET or CMZ. 4. From the results of the passive hemagglutination (PHA) test, no
      antibody against TAZ/PIPC, TAZ or PIPC was detected. 5. In direct Coombs' test
      using human blood, TAZ/PIPC, TAZ, PCG and CET showed positive reactions at 20-80,
      5-20, 80 and 10-20 mg/ml, respectively. 6. The results of a test on in vitro
      covalent binding activity with human serum albumin indicated that the order of
      binding potency was CET > CMZ > ABPC > PCG = PIPC > TAZ under the physiological
      condition (pH 7.2-7.4), and was CMZ > CET > ABPC > PIPC > TAZ > PCG under the
      alkaline condition (pH 10.0-10.5), respectively.

PMID- 7830291
TI  - [Mutagenicity tests of tazobactam/piperacillin, tazobactam and piperacillin].
AB  - As a part of safety tests of tazobactam/piperacillin (TAZ/PIPC), the reverse
      mutation tests using bacteria, the chromosomal aberration tests using cultured
      cells and the micronucleus tests using male mice were conducted in order to
      evaluate the in vitro and in vivo mutagenicity of TAZ, PIPC, TAZ/PIPC. 1. The
      reverse mutation tests were carried out on TAZ, PIPC and TAZ/PIPC at dose ranges,
      where few antibacterial effects could be detected, using Salmonella typhimurium
      strains TA100, TA1535, TA98 and TA1537, and Escherichia coli WP2uvrA. All of
      three test articles showed that no significant increases were observed in the
      number of colonies in all tester strains in both systems, with and without
      mammalian metabolic activation (S9 Mix), as compared with solvent controls. 2.
      The chromosomal aberration tests were carried out on these test articles using
      cultured Chinese hamster lung cells (CHL). The cells were treated with TAZ, PIPC
      or TAZ/PIPC at the doses of 2.5, 5.0 and 10 mM with and without S9 Mix. In the
      test of PIPC with S9 Mix, the dose of 1.25 mM was set in addition to the three
      doses. The incidences of structural- and numeral-aberration were 0-3% in the
      absence or presence of mammalian metabolic activation system, and no significant
      increases were observed in the incidence of chromosomal aberrations as compared
      with solvent controls. 3. The micronucleus tests were carried out at doses of 625
      5000 mg/kg of TAZ or TAZ/PIPC, or at 625-2500 mg/kg of PIPC. The femoral marrow
      cells were 48 h after administering intravenously to CD-1 male mice. The
      frequencies of polychromatic erythrocyte with micronuclei were 0.02-0.17%, 0.02
      0.10% and 0.03-0.07% in the groups treated with TAZ, PIPC and TAZ/PIPC,
      respectively, and no significant increases were observed with dose dependence.
      The results indicated that these test articles were negative in the assessment
      standard using the background data. 4. The present study indicates that TAZ, PIPC
      and TAZ/PIPC have no in vitro and in vivo mutagenic potential.

PMID- 7830292
TI  - Normal plain film examination of the heart and great arteries in the adult.
AB  - A plain film chest examination is nearly always obtained in the management of
      patients suspected of cardiac disease. The wealth of diagnostic information
      obtained from posteroanterior and lateral thoracic images is often essential data
      needed to direct the evaluation and treatment of these patients. Appreciation of
      the normal cardiac, pulmonary, and great vessel anatomy provides a basis for the
      identification and characterization of the abnormal. Furthermore, the chest
      radiograph provides an important means to appreciate the pathophysiologic
      mechanisms underlying the morphologic changes in patients with congenital heart
      disease.

PMID- 7830293
TI  - Magnetic resonance imaging in adult congenital heart disease.
AB  - Some patients with congenital cardiac anomalies develop their first symptoms as
      adults, and many more will survive to adulthood with congenital lesions that have
      been treated surgically. Magnetic resonance imaging (MRI) currently provides
      sufficient morphological information to allow the anatomical diagnosis of
      congenital abnormalities involving the heart and the great arteries. Newer MR
      techniques have also been developed that provide functional information such as
      measurements of valve gradients, stroke volumes, regurgitant volumes, and shunt
      volumes. Cardiac evaluation utilizing MR techniques may soon replace cardiac
      catheterization for the preoperative diagnosis of congenital heart disease and
      its long-term follow-up.

PMID- 7830294
TI  - Congenital abnormalities of the thoracic aorta presenting in the adult.
AB  - Congenital variations in the development of the thoracic aorta are common.
      Although there is a spectrum of disease in all age groups, arch anomalies that
      present in childhood and those that present in the adult tend to be of differing
      types. Imaging of the arch and its branches, the descending aorta, and the ductus
      arteriosus or ligamentum arteriosum define the morphology of the arch and permit
      a reasonable prediction of accompanying congenital heart disease and/or vascular
      ring.

PMID- 7830295
TI  - Radiologic findings of normal and compromised thoracic venous catheters.
AB  - We review the radiologic findings of normal positioning, malpositioning, and
      complications related to the more commonly used thoracic venous catheters. These
      include central venous catheters, long-term central venous access catheters, and
      pulmonary artery catheters. The radiologist plays an important role in the early
      recognition of the complications of these catheters. The daily practice of chest
      radiology is intimately related to the evaluation of the integrity and correct
      placement of thoracic venous catheters. The purpose of this pictorial essay is to
      review radiologic findings of normal positioning, malpositioning, and
      complications related to the more common devices used, including central venous
      catheters, long-term central venous access catheters, and pulmonary artery
      catheters. Many of the complications described are serious and may remain
      unrecognized for a long time; this may cause incorrect diagnosis and delayed
      treatment. The radiologist plays an important role in the early recognition of
      these complications. Malpositioning and complications often are more easily
      diagnosed with contrast-enhanced studies and computed tomography.

PMID- 7830296
TI  - Anomalous origin of posterior descending artery from left anterior descending
      artery with unusual intraseptal course.
AB  - The posterior descending artery (PDA) arises from the right coronary artery (RCA)
      in approximately 85% of people; only in from 10 to 15% does it arise from the
      circumflex artery. We report an unusual case of origin of the PDA from a branch
      of the left anterior descending artery (LAD). The PDA passed through the
      interventricular septum before it reached the posterior interventricular groove.

PMID- 7830297
TI  - Left ventricular pseudoaneurysm.
AB  - Cardiorrhexis, or rupture of the myocardium, is an uncommon event after acute
      myocardial infarction. It has serious consequences such as acute hemopericardium,
      cardiac tamponade, and sudden death. If the rupture remains enclosed by
      surrounding adhesions or an intact visceral pericardium, a pseudoaneurysm may
      develop. We describe a rather typical presentation of a pseudoaneursym of the
      left ventricle with resultant congestive heart failure after a silent myocardial
      infarction, and we point out the utility of prompt ultrasound examination in this
      clinical setting.

PMID- 7830298
TI  - Congenital heart disease in the adult: clinical approach.
AB  - The remarkable advances in diagnostic techniques and in the surgical and medical
      care of infants and children with congenital heart disease have resulted in an
      impressive increase in longevity. Congenital heart disease in adults has emerged
      as a specialized area of cardiovascular interest. In response, special
      multidisciplinary facilities have been developed for the comprehensive care of
      adults with congenital heart disease. The scope of the discipline is relatively
      broad and includes unoperated survival patterns; survival patterns after surgery
      or interventional catheterization; a host of medical considerations; surgical
      considerations (operation and reoperation, cardiac catheterization as a
      therapeutic intervention, and noncardiac surgery); and the important problems of
      postoperative residua and sequelae. The purpose of this communication is to call
      attention to this subspecially and to excite the interest of radiologists in
      certain imaging aspects of congenital heart disease in adults.

PMID- 7830299
TI  - Iatrogenic tracheobronchial perforation in infants.
AB  - We describe the clinical and radiographic features of four premature infants with
      acute iatrogenic tracheobronchial perforation by endotracheal tube (ETT)
      placement. One tube penetrated posteriorly into the esophagus, one directly
      through the carina; one perforated the right main bronchus posteriorly; and one
      breached the site of a recently repaired tracheoesophageal fistula. In only one
      infant was the intubation procedure clinically recognized to be traumatic.
      Radiographs obtained for tube placement demonstrated inferior malposition of the
      ETT in all four babies, decreased pulmonary aeration in three of four, acute
      retrocardiac infraazygos pneumomediastinum in three of four, and acute pleural
      effusion in one of four. Two infants developed progressive air leak and died in
      spite of drainage with multiple chest tubes; two survived and did well with
      conservative management. An additional eight cases have been previously reported,
      with an overall mortality of 58%. Prompt recognition of acute airway perforation
      can be lifesaving. Unexpected respiratory distress after intubation associated
      with acute infraazygos pneumomediastinum strongly suggests this entity.

PMID- 7830300
TI  - The Glenn Face Down Pillow: an aid to performance of prone radiologic procedures.
AB  - The ease of performing computed tomography (CT)-guided radiologic procedures with
      the patient in the prone position can be compromised by patient discomfort. This
      is especially true during transthoracic needle aspiration biopsy when sedation or
      analgesia may interfere with the patient's ability to cooperate. The Glenn Face
      Down Pillow, a foam cushion with air vents that allows unimpeded respiration with
      the patient entirely prone, was tested in 34 such biopsies over a 1-year period.
      Patient compliance was better than with conventional cushions and padding, and
      procedural problems related to motion from cramping and stiffness were reduced.

PMID- 7830301
TI  - Viral hepatitis B and D--preventive aspects.

PMID- 7830302
TI  - Emergence of multi-drug resistance among beta-lactamase producing Salmonella.
AB  - Multi-drug resistant strains of Salmonella isolated from blood and bone marrow
      cultures of pyrexial patients received from physicians, hospitals and different
      clinics were studied from May to November, 1993. Of 2143 samples collected,
      424(20%) cases yielded the growth of different organisms. Out of these 266(63%)
      were positive for Salmonella strains. The strains isolated were Salmonella typhi
      239(90%) and Salmonella paratyphi A 27(10%). Two hundred twenty (82%) strains of
      Salmonella showed increased beta-lactamase activity and an alarming increase in
      resistance against commonly used antibiotics for enteric fever.

PMID- 7830303
TI  - Carriage of beta haemolytic streptococci (BHS) in pregnant women and acquisition
      by neonates.
AB  - Beta Haemolytic Streptococci(BHS) carriage rate in pregnant women during labour
      and its acquisition by their newborns just after birth was investigated in 60
      mother baby pairs. The carriage rate of group B Streptococci (GBS) was 11.6%,
      acquisition rate by newborns of carrier and non-carrier mothers was 85.7% and
      1.8% respectively. A total of 28.5% newborns were carrying GBS on all the skin
      sites and were heavily colonized and therefore, at higher risk of developing
      early onset of Streptococcal infections. Penicillin G and Ampicillin were most
      effective antibiotics against GBS.

PMID- 7830304
TI  - Active management of preterm labour and preterm prelabour rupture of membranes.
AB  - Hundred cases of preterm labour (before 36 weeks) with cervix 4 cm or less
      dilated and preterm prelabour rupture of membranes (excluding cases of uterine
      overdistension, maternal medical disorders and fetal congenital abnormalities)
      were treated with bed rest and sedation. Labour set in within 2-6 days with high
      fetal morbidity and mortality. Another fifty similar patients were given in
      addition to rest in hospital for 48 hours, 1000 ml of 5% dextrose in six hours,
      intravenous antibiotics (after sending off cultures from the vagina per
      speculum), corticosteroids and a single dose of analgesia/sedation injection. In
      85% painful contractions ceased and membranes stopped leaking until near term. In
      10% painful contractions ceased, but leakage continued for 2-7 weeks, and the
      gain in intrauterine life led to 100% neonatal survival with short hospital stay
      in the neonates born after 31 weeks. Only 5% failed to respond to treatment and
      after delivery these premature neonates developed pneumonia and septicaemia from
      the same organisms that were colonizing their maternal genital tract and had
      entered the fetus via the infected amniotic fluid. It is recommended that all
      patients in preterm labour or preterm prelabour rupture of membranes (excluding
      overdistension) be given besides bed rest and sedation, corticosteroids and
      antibiotics intravenously for 48 hours and then orally for eight more days.
      Tocolytics are not recommended. This regime saves babies.

PMID- 7830305
TI  - Immediate haemorrhoidectomy for thrombosed fourth degree haemorrhoids.

PMID- 7830306
TI  - Prevalence of HBV infection in health care personnel.

PMID- 7830307
TI  - Myasthenic crisis induced by chemotherapy in treatment of invasive thymoma.

PMID- 7830308
TI  - Endometrioid carcinoma of the ovary: an unusual tumour in young females.

PMID- 7830309
TI  - Cryptic disseminated tuberculosis--an often missed diagnosis.

PMID- 7830310
TI  - [Bacterial structures determined by rapid-freezing technique].

PMID- 7830311
TI  - [Bacterial adherence and infections in the human intestines: histological and
      bacteriological basis for oral vaccine development].

PMID- 7830312
TI  - [Pili and colonization factors of Vibrionaceae].

PMID- 7830313
TI  - [Recent immunological study of leprosy].

PMID- 7830314
TI  - [Studies on infections and host defense through cytokines].

PMID- 7830315
TI  - [Action of Clostridium perfringens alpha toxin].

PMID- 7830316
TI  - [Suppression of autoimmune disease by induction of oral tolerance to self
      antigen].

PMID- 7830317
TI  - [Changing profile of mycobacterial infection: current understanding].

PMID- 7830318
TI  - [A novel clostridial toxin which inhibits neuromuscular transmission].

PMID- 7830319
TI  - [Formidable streptococcal infections].

PMID- 7830320
TI  - [A simple method for differentiation of hydrogen sulfide-producing bacteria by
      the pH-dependent EDTA-sensitivity test].
AB  - The pH-dependent EDTA-sensitivity test was performed to differentiate several
      strains of bacteria forming black colonies by the production of hydrogen sulfide
      on TCBS (thiosulfate-citrate-bile salt-sucrose agar) medium (tentatively
      designated as hydrogen-sulfide production bacteria). Two halotorelant strains of
      16 hydrogen sulfide-producing strains showed the same bacteriological properties
      and isoprenoid quinone type as did a reference strain of Proteus mirabilis and
      were classified into the EDTA-insensitive group as were P. mirabilis and P.
      vulgaris. On the other hand, the other 14 halophilic strains, showing similar but
      not identical bacteriological properties or the isoprenoid quinone type to those
      of Shewanella putrefaciens IFO 3908, were classified into the "EDTA-sensitive (at
      pH 5)" group as were some species of the genus Vibrio. By the same sensitivity
      test, S. putrefaciens IFO 3908 was classified into the "EDTA-sensitive (at any
      pH)" group. These results indicate that the pH-dependent EDTA-sensitivity test is
      useful for differentiation of bacterial isolates producing hydrogen sulfide and
      having similar bacteriological properties.

PMID- 7830321
TI  - [Identification of group C Streptococcus with Helix pomatia lectin in use for
      blood grouping].
AB  - The lectin anti-AHP (Helix lectin) obtained from the albumen gland of an edible
      snail, Helix pomatia, was used for the identification of group C streptococci.
      All 1,045 strains of group C streptococci (S. equisimilis, S. zooepidemicus, and
      S. dysgalactiae) were agglutinated with the Helix lectin, but none of the 12,264
      strains of group A, 1,346 strains of group G, 330 strains of group B, and 121
      strains of other streptococcal groups was not. A few strains of S. equisimilis
      which belongs to group C have on the cell surface specific T antigen of group A
      streptococci, but it did not affect the agglutination with Helix lectin. Some
      strains of S. milleri carrying or not carrying group G specific carbohydrate and
      S. sanguis with group H antigen were agglutinated with the Helix lectin (Anti
      AHP). This suggests that terminal N-acetyl-D-galactsamine of the cell-wall
      carbohydrate of these bacteria reacts with the Helix lectin (Anti-AHP).
      Therefore, the Helix lectin is a very useful tool for identification of group C
      streptococci.

PMID- 7830322
TI  - [Monoclonal antibody mNI-11 strongly induces homotypic cell aggregation of
      monocyte-like cell line U937: effects of conditioned medium and cytochalasin B].
AB  - A mouse monoclonal antibody (mAb), designated as mNI-11, has been produced. This
      mAb strongly induced homotypic cell aggregation (HCA) of monocyte-like cell line
      U937 cultured with conditioned medium derived from PHA-stimulated peripheral
      blood mononuclear cells and cytochalasin B. HCA occurred at an optimal
      temperature of 37 C but not 4 C. mAbs to CD18 (lymphocyte function-associated
      antigen-1 beta; LAF-1 beta) and CD54 (intercellular adhesion molecule-1; ICAM-1)
      completely inhibited this HCA. These results suggest that mNI-11 strongly induces
      HCA of the U937 cells in an activated form after stimulation with conditioned
      medium and cytochalasin B.

PMID- 7830323
TI  - Ventricular wall stress revisited. A keystone of cardiology.
AB  - Wall stress has been used as one of the parameters of myocardial mechanics. The
      present review focuses on recently developed data on ventricular wall stress,
      especially in relation to other newly developed areas in cardiology. In
      hypertensive hearts, there is a broad continuous spectrum in the structural and
      functional changes: those with low wall stress (inappropriate hypertrophy), those
      with normal wall stress (appropriate hypertrophy) and those with high wall stress
      (inadequate hypertrophy). Among them, the responses to neurohumoral stimuli are
      various, and their clinical features and courses also varied. These differences
      in wall stress among the different categories of hypertensive hearts may be
      caused by the variable influences of non-mechanical factors, such as molecular,
      metabolic and neurohumoral ones. Wall stress is an essential determinant of
      myocardial oxygen consumption, and is also an important determinant of the
      myocardial contractile state and diastolic function. In contrast to excitation
      contraction coupling, contraction-excitation feedback has been studied,
      suggesting the importance of wall stress regulating electrical phenomena. The
      interrelationship between mechanical factors (including wall stress) and non
      mechanical factors (including molecular, metabolic, neurohumoral and genetic
      ones) has been investigated intensively. In conclusion, wall stress (or force on
      the myocardial cell) may be a keystone in cardiology, relating to each of the
      cardiac phenomena. If wall stress deviates from the normal range, even with
      compensatory mechanisms, severe cardiac events occur. The compensatory mechanisms
      for wall stress may act as a risk factor on the heart, especially when the wall
      stress remains outside the normal range.

PMID- 7830324
TI  - Effect of two different therapeutic approaches on total and cardiovascular
      mortality in a Cardiovascular Study in the Elderly (CASTEL).
AB  - Although limited numbers of elderly subjects have occasionally been included in
      population-based studies, only a few studies have been conducted specifically on
      elderly hypertensives, and practically none at a population level. We studied 655
      hypertensive subjects from a cohort of 2,254 elderly subjects. The intervention
      consisted of the creation of a Hypertension Outpatients' Clinic under our
      auspices but with complete co-operation from general practitioners, randomizing
      the identified hypertensive patients into pre-established therapeutic drug
      regimens, and early follow-up recording of mortality for 7 years. The drugs used
      were clonidine (n = 61), nifedipine (n = 146) and the fixed combination of
      atenolol+chlorthalidone (n = 144); 304 subjects underwent "free therapy" by their
      personal physicians without any special intervention. There were 1,404
      normotensive subjects. Overall 7-year follow-up mortality was 34.9% in the
      hypertensive subjects receiving "free therapy", 22.5% in those receiving "special
      care", and 24.2% in the normotensives. Cardiovascular mortality was respectively
      23.7%, 12.2%, and 12.0%. Overall and cardiovascular annual cumulative mortality
      were significantly lower in the << special therapy >> than in the << free therapy
      >> group. The fixed combination of atenolol and chlorthalidone reduced mortality
      below that of the normotensives, independent of other cardiovascular risk
      factors.

PMID- 7830325
TI  - Malignant hypertension in north west India. A hospital based study.
AB  - One hundred and thirty-five patients with malignant hypertension seen over a
      period of 11 years (1979 to 1989) at a referral hospital were analyzed to
      characterize the clinical features and etiology of this disease. Ninety male and
      45 female patients with an average age of 38.2 +/- 1.4 years were studied.
      Malignant hypertension was the presenting feature in 68 patients. The etiology
      included essential hypertension in 88 patients and a secondary cause in 47
      patients. Secondary causes included a renovascular etiology in 20 patients, renal
      parenchymal disease in 19, pheochromocytoma in 6 and Conn's syndrome and adrenal
      carcinoma in one patient each. Among the 20 patients with renovascular
      hypertension, Takayasu's arteritis was seen in 15 (75%). The mean age of patients
      with essential hypertension was 41.7 + 1.14 years while the mean age in patients
      with secondary hypertension was 33.2 + 1.96 years. Duration of preexisting
      hypertension was longer in essential hypertensives (2.42 + 0.45 years) than in
      patients with secondary hypertension (1.27 + 0.41 years, p < 0.05). Raised serum
      creatinine was seen in 93 patients. Seventy-seven patients had left ventricular
      hypertrophy on ECG. Ninety-six patients were followed for a period ranging from
      18 months to 10 years (mean 32 months). Sixteen patients died during hospital
      stay while 6 patients died during the follow-up period. The deaths were related
      to the effects of uncontrolled hypertension including, renal failure (11), stroke
      (6), congestive cardiac failure (3) and myocardial infarction (1).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7830326
TI  - Procainamide-induced changes in reentrant ventricular tachycardia with special
      reference to the tachycardia-interrupting critical paced cycle length during
      transient entrainment with rapid pacing.
AB  - With rapid ventricular pacing, sustained ventricular tachycardia (VT) is often
      entrained and interrupted at a critical paced cycle length. In this paper, the
      possible mechanism and determinant of the critical cycle length interrupting VT
      are addressed. Sixteen consecutive patients underwent rapid ventricular pacing in
      18 morphologically distinct sustained VTs before and after procainamide. The VT
      morphology was identical before and after the drug. The VT origin was determined
      by endocardial mapping as the earliest site of activation of VT and an electrode
      catheter was located at the site. Rapid pacing was performed to entrain VT and
      repeated in 10 msec decrements of cycle length until VT was interrupted at a
      critical paced cycle length which was defined as the block cycle length. The
      effective refractory period was measured at the pacing site. The paced QRS
      duration and the local conduction time were measured and used as indices of
      conduction time in the normal myocardium. VT was entrained and interrupted in all
      patients. At the block cycle length, initial constant fusion was replaced
      abruptly by the fully paced QRS complex. At the same time, the local electrogram
      at the site of VT origin showed changes in the morphology and the timing of
      activation which were identical to those of the fully paced beat. This loss of
      fusion and the changes in the local electrogram were considered to be a result of
      orthodromic block and the block cycle length was assumed to represent the cycle
      length at which 1:1 conduction fails in the area of slow conduction. After
      procainamide, both the VT cycle length and the block cycle length were prolonged
      to a similar degree (p < 0.001) but the relative degree of change varied from
      patient to patient. The paced QRS duration and the conduction time were prolonged
      by procainamide but in smaller degrees than the cycle length of VT or the block
      cycle length (p < 0.02-01). The effective refractory period at the pacing site
      and the QT interval showed small changes after procainamide. The
      postrepolarization refractoriness rather than the duration of action potential
      can be responsible for the procainamide-induced prolongation of the block cycle
      length, and the block cycle length might be used as a new index to characterize
      the electrophysiologic property of the VT circuit and also the action of
      antiarrhythmic drugs.

PMID- 7830327
TI  - Atrial demand pacing in patients with symptomatic sick sinus syndrome.
AB  - Atrial demand pacing provides a physiological, simply implemented, and less
      costly alternative of cardiac stimulation in symptomatic sick sinus syndrome
      (SSS) patients. Hindrance from widespread use stems mainly from the potential
      development of high degree AV block and persistent atrial fibrillation. A
      reappraisal of atrial pacing is now justified as we gain more clinical
      information. In this study we examined retrospectively the clinical course of 22
      well-selected SSS patients paced in AAI mode for 30 +/- 29 months. Two patients
      had infrequent short-run atrial tachyrhythmia before implantation. There was an
      early lead dislodgement which required repositioning later. Three acute threshold
      increments were noted which necessitated a change in atrial pacing site in one
      and short-term steroid use in the other two. No other sensing, pacing or
      operative complication occurred and all pacing systems performed well. AII
      patients survived during follow-up and no patient developed congestive heart
      failure, though depressed left ventricular function was found in three
      preoperatively. No high degree AV block was encountered. Four patients presented
      paroxysmal atrial fibrillation (PAF) 25 +/- 16 months after the procedure, of
      whom one developed chronic atrial fibrillation. No single factor predicted the
      development of PAF. Resumption of normal pacemaker function always occurred
      immediately in the pause following cessation of PAF and no revision of pacing
      mode was required in the patient with chronic AF. Symptomatic relief was obtained
      in all patients. In summary, single chamber, single rate atrial pacing remains a
      physiologic, reliable, economic and easily implemented pacing modality affordable
      to a number of sick sinus patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7830328
TI  - Echocardiographic findings in some metabolic storage diseases.
AB  - This study was planned to determine the presence and extent of cardiac
      involvement in metabolic storage diseases, including types I and II glycogenoses,
      Gaucher and Neimann-Pick diseases, galactosialidosis and mucopolysaccharidosis. M
      mode, 2-dimensional and Doppler echocardiographic studies were used for the
      determination of left ventricular wall thickness, systolic function, anatomic
      derangement, valvular dysfunction and left ventricular diastolic function in the
      patient and control groups. In 19.35% of the cases valvular involvement, and in
      59.26% thickening of the left ventricular wall due to metabolic storage, was
      found. Left ventricular systolic function was in the normal range. The diastolic
      mitral flow patterns of the cases showed obstructive type changes. It can be
      concluded that in this study, besides previously described cardiovascular
      changes, some new findings have been detected by means of echocardiography in
      patients with metabolic storage diseases.

PMID- 7830329
TI  - Coronary blood flow autoregulation and flow heterogeneity in the stunned heart.
AB  - We used an anesthetized swine model of regionally "stunned" myocardium to
      determine the effect of stunning on coronary autoregulation and blood flow
      heterogeneity. In 18 domestic swine, stunning was accomplished by reducing blood
      flow to the left anterior descending coronary artery (LAD) by approximately 75%
      of baseline for 15 min and restoring it to normal for 1 hour. We quantified
      coronary autoregulation using both the slope of coronary pressure-flow curves and
      an autoregulation index. We quantified blood flow heterogeneity using radioactive
      microspheres to determine the variability in flow (dispersion index) among forty
      200 mg segments of myocardium from the center of the stunned, LAD-perfused left
      ventricle. Before and after stunning, we measured autoregulation, myocardial
      blood flow and flow heterogeneity, as well as hemodynamic indices of myocardial
      oxygen demand. Fifteen min of ischemia and 1 hour of reperfusion produced both a
      46% reduction in mechanical function, and a 7% drop in systemic arterial
      pressure, but not change in heart rate or rate pressure product. Myocardial
      oxygen consumption was 15% reduced and myocardial blood flow 16% reduced in the
      stunned myocardium when measured at one hour of reperfusion. Fifteen min after
      reperfusion, the slope of the coronary pressure flow plots and the coronary
      venous oxygenation were increased whereas the autoregulation index decreased.
      These findings all indicate reduced autoregulation during early reperfusion.
      However, after one hour of reperfusion, the slope of the coronary pressure-flow
      relation (0.41 +/- 0.19 vs. 0.48 +/- 0.26 ml.100 g-1.min-1.mmHg-1) and the
      autoregulation index (0.43 +/- 0.16 vs. 0.30 +/- 0.32) were unchanged from
      control measurements (p > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7830330
TI  - Hyperresponsiveness of cardiac muscles to histamine in reserpine-treated guinea
      pigs.
AB  - The hyperresponsiveness of cardiac tissue to histamine following treatment with
      reserpine was pharmacologically characterized. Guinea pig hearts were isolated 24
      hours after intraperitoneal administration of 5 mg/kg reserpine. This treatment
      resulted in a complete depletion of tissue norepinephrine. Reserpine treatment
      potentiated the positive inotropic response of isolated perfused hearts to
      histamine at doses ranging from 0.3 to 3 micrograms (23 to 57% increase for
      reserpine-treated animals vs. 14 to 32% increase for control animals). Isolated
      left ventricular papillary muscle of reserpine-treated guinea pig hearts also
      showed hyperresponsiveness to histamine at concentrations of 0.1 microM or
      greater. The hyperresponsiveness of the papillary muscle contraction of the
      reserpine-treated animals to histamine was abolished in the presence of 1 microM
      cimetidine, but not attenuated in the presence of 1 microM diphenhydramine. This
      hyperresponsiveness was not modified by 1 microM bunazosin or 1 microM
      propranolol. The results suggest that H2-receptor mediated action plays a role in
      the hyperresponsiveness of cardiac muscles to histamine.

PMID- 7830331
TI  - Ca2+ waves and intracellular Ca2+ concentration in guinea pig and rat myocytes.
AB  - We measured [Ca2+]i of guinea pig and rat myocytes with Ca2+ waves, using fura-2
      fluorescence image processing. In guinea pig myocytes, Ca2+ waves were absent
      during the control perfusion period, but could be induced by the addition of
      strophanthidin (100 microM) or sodium cyanide (NaCN: 2 mM) to the perfusate. The
      [Ca2+]i increased from the control values of 69 +/- 5 nM and 46 +/- 2 nM, to 263
      +/- 9 (p < 0.05 vs. control) nM and 225 +/- 20 (p < 0.05) nM, respectively, when
      cells exhibited Ca2+ waves. Although 13% (16 of 121) of the rat myocytes
      displayed Ca2+ waves during the control perfusion, the [Ca2+]i with Ca2+ waves
      (56 +/- 9 nM) did not differ from [Ca2+]i in the absence of Ca2+ waves (54 +/- 3
      nM). Ca2+ waves were induced by the perfusion with a high Ca2+ solution (24.5
      microM) or NaCN (2 microM), and [Ca2+]i increased from the control values of 67
      +/- 11 nM and 74 +/- 5 nM, to 231 +/- 41 (p < 0.05 vs. control) nM and 266 +/- 64
      nM, respectively, when cells exhibited Ca2+ waves. The Ca2+ waves were abolished
      by the removal of extracellular Ca2+, or by the perfusion with ryanodine (10
      microM) or caffeine (20 mM). In conclusion, it was shown that Ca2+ waves were due
      to oscillatory Ca2+ release and that the absolute value of [Ca2+]i is important
      for the appearance of Ca2+ waves in guinea pig and rat myocytes.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7830332
TI  - Intracoronary acetylcholine-induced prolongation of the QT interval and Torsade
      des Pointes in long QT interval syndrome.
AB  - A 75-year-old female had syncopal episodes from Torsade des Pointes (TdP). Her
      electrocardiogram showed a prolonged QT interval which was not associated with
      electrolyte imbalances or drug therapy. Similar electrocardiographic
      abnormalities were found in three family members. Electrophysiologic study showed
      a mildly prolonged effective refractory period of 260-290 msec, but no
      tachyarrhythmia was induced. Coronary arteriography was normal but intracoronary
      acetylcholine unexpectedly induced a prolongation of the QT interval and TdP.
      Direct action of acetylcholine on the ventricular muscle was suggested.

PMID- 7830333
TI  - A case of arrhythmogenic right ventricular dysplasia with atrial flutter.
AB  - A 57-year-old male who had arrhythmogenic right ventricular dysplasia (ARVD) with
      recurrent atrial flutter (AF) is reported. The patient had more frequent episodes
      of AF than of ventricular arrhythmias. Magnetic resonance imaging,
      echocardiography and right ventriculography revealed dilatation of the right
      ventricle and endomyocardial biopsy specimens from the right ventricle showed
      findings which were compatible with ARVD. The left ventricular specimen, however,
      also revealed a loss of myocytes and interstitial fibroelastic changes. The
      present case demonstrates an overlap of post-inflammatory or primary
      endomyocardial fibroelastic changes with ARVD.

PMID- 7830334
TI  - AA-amyloidosis presenting with chronic diarrhea and cardiac manifestations.
AB  - In secondary amyloidosis (AA type), clinically significant cardiac and
      gastrointestinal involvement are uncommon, in contrast to the primary type. We
      report a case presenting with chronic diarrhea and cardiac manifestations who was
      diagnosed as having AA-amyloidosis with unknown predisposing illness based on
      endomyocardial, rectal and subcutaneous fat tissue biopsies.

PMID- 7830335
TI  - High rates of Ki-ras point mutation in both intra- and extra-hepatic
      cholangiocarcinomas.
AB  - The presence of the Ki-ras gene mutations in 14 cases of intrahepatic
      cholangiocarcinoma (IHC) and nine cases of extrahepatic cholangiocarcinoma (EHC)
      were investigated by polymerase chain reaction-single strand conformation
      polymorphism analysis. To obtain enriched tumor cell DNA, the microdissection
      method was used on formalin-fixed paraffin-embedded tissue sections. Point
      mutations at codon 12 of the Ki-ras gene were detected in seven (50%) of the 14
      cases of IHC and six (67%) of the nine EHC cases. In all but one of the ras gene
      mutation cases, G to A transitions in the second position of codon 12 were
      detected, the exception being a G to T transition in the same position in one
      IHC. No point mutations were detected at codon 13 or 61 in either IHC or EHC.
      Furthermore, there was no demonstrable correlation between Ki-ras mutation and
      patient age, tumor Stage, histological findings or prognosis. The present results
      demonstrated a higher participation of Ki-ras gene mutations in EHC than found in
      previous studies, and provided a confirmation and extension of the results
      earlier reported by Tada et al. and Tsuda et al. for IHC.

PMID- 7830336
TI  - Detection of nodular lesions in the lung helical computed tomography: comparison
      between 360 degrees and 180 degrees reconstruction algorithms.
AB  - The present study has evaluated helical computed tomography (HS-CT) performed at
      a fast couch-top sliding speed (20 mm/sec, sufficient to cover the entire lung
      field during the holding of a single breath) with regard to its ability to detect
      pulmonary nodules in patients with metastatic lung disease. The detectability of
      lesions by HS-CT was compared between 360 degrees and 180 degrees reconstruction
      algorithms. The subjects were eight consecutive patients with metastatic lung
      tumors, in whom 214 lesions had been detected by conventional CT. The average
      diameter of the nodules detected was 7.7 mm (2-22 mm). To scan the entire lung,
      we first used conventional CT (10-mm slice thickness, 10-mm stepping) and then HS
      CT with a couch-top speed of 20 mm/sec and a tube current of 50 mA. Both 360
      degrees and 180 degrees algorithms were used to reconstruct images at intervals
      of 20 and 10 mm from HS-CT data. Detection rates of 79% for 20-mm images and 94%
      for 10-mm images were achieved with the 360 degrees algorithm. Detection rates of
      81% for 20-mm images and 99% for 10-mm images were achieved with the 180 degrees
      algorithm. The detection of nodules was greater for 10-mm images than 20-mm
      images (P < 0.01). There was no significant difference between the 360 degrees
      and 180 degrees algorithms. Images acquired using the 180 degrees algorithm,
      however, depicted lesions with greater sharpness than those acquired using the
      360 degrees algorithm. It is presumed that they indirectly show the superiority
      of the 180 degrees algorithm over the 360 degrees algorithm. HS-CT should prove a
      useful screening technique for lesions in the lung field.

PMID- 7830337
TI  - Tegafur-uracil (UFT) plus folinic acid in advanced rectal cancer.
AB  - We previously reported positive results to Tegafur-Uracil (UFT) chemotherapy in a
      group of patients with advanced rectal cancer. We have continued the study and
      now report the effectiveness of UFT plus folinic acid (FA) in 52 patients with
      advanced rectal cancer. The therapeutic schedule was UFT, 600 mg/m2/day x 14 days
      p.o. + FA, 90 mg/m2/day x 14 days p.o. Fifty-two out of a total of 56 patients
      were evaluated for response and toxicity. A higher incidence of positive
      responses in patients without previous chemotherapy was appreciated. Twenty-one
      of the 52 evaluated patients showed a partial response (PR). Responses were
      strongly correlated with previous chemotherapy (14/20; 70% PR of cases without
      previous chemotherapy vs 7/32; 22% of cases with previous chemotherapy). All
      responding patients came forward with a median time to progression of 8.2 months
      (19.6 months for patients without previous chemotherapy vs 7.7 months for
      patients with previous chemotherapy, P < 0.01). We concluded that the UFT plus FA
      could be a treatment of choice for patients with advanced rectal cancer.

PMID- 7830338
TI  - Robb-Smith type malignant histiocytosis associated with a mediastinal germ cell
      tumor.
AB  - A 22-year-old Japanese man with a mediastinal germ cell tumor with mixed teratoma
      and hepatoid alpha-fetoprotein positive, and glandular yolk sac components, also
      demonstrated widely disseminated malignant histiocytosis involving the lungs,
      liver, pancreas, spleen, bone marrow and lymph nodes. Sensitivity to chemotherapy
      was acute and the patient died of disseminated intravascular coagulation syndrome
      within four months of his initial presentation.

PMID- 7830339
TI  - Malignant localized fibrous tumor of the peritoneum arising in its benign
      counterpart.
AB  - We report a case of malignant localized fibrous tumor (LFT) of the peritoneum in
      a 78-year-old man. The tumor was pedunculated and the malignant area completely
      surrounded by its benign counterpart, forming "a nodule within a nodule"
      appearance. Histologically, the latter area showed typical features of a benign
      LFT, while the former fulfilled the criteria of a malignant LFT as defined by
      England et al.; i.e., one being rich in fibroblastic spindle cells with plump and
      atypical nuclei, hyalinized stroma and mitotic figures. Immunohistochemically,
      spindle cells in both portions of the tumor were positively stained for vimentin
      but completely negative for keratin (AE1/AE3), S-100 protein and desmin. There
      was a significant increase in proliferating cell nuclear antigen (PCNA)-positive
      cells in the malignant portion (80%) in comparison with the benign portion (45%).
      To date, we are not aware of any report on a malignant localized fibrous tumor in
      association with a benign counterpart. The unique association, therefore,
      prompted us to report our experience, and suggests the possibility of malignancy
      developing in the benign localized fibrous tumor.

PMID- 7830340
TI  - Epididymis metastasis from colon carcinoma: a case report and a review of the
      Japanese literature.
AB  - A 56-year-old Japanese man in whom a descending colon carcinoma had been resected
      underwent a high orchitectomy for metastatic epididymis from the colon.
      Metastatic carcinoma from the digestive organs to the spermatic cord (SC) and/or
      the intrascrotal contents (ISC) is rare. Fifty-four Japanese patients with
      metastasis from the digestive organs to the SC and/or the ISC were analyzed. The
      most frequent primary site was the stomach and the most frequent metastatic site
      was the spermatic cord. Our patient was the first to exhibit metastasis from the
      colon to the epididymis. A primary site was identified in 24 patients subsequent
      to the metastatic tumor. Twenty patients had other organ metastasis. The
      prognosis for SC and/or ISC metastasis patients is poor. Our patients has
      survived for 18 months following his orchitectomy with no other organ metastasis
      (31 months after the primary operation). In our patient, monoclonal estrogen
      receptor staining was negative; however, further study must be undertaken.

PMID- 7830341
TI  - [Health effects of fluorine and its compounds].
AB  - Fluoride, the ionic form of fluorine, is a natural component of the biosphere and
      13th most abundant element in the crust of the earth. It is, therefore, found in
      a wide range of concentrations in virtually all inanimate and living things. Many
      trace elements perform a definite function in human metabolism and the question
      of the value of fluoride, always found in the body, has been raised. Much
      evidence suggesting that the inclusion of fluoride in drinking water has
      beneficial as well as adverse effects on human health was obtained. Either alone
      or in combination with calcium and/or vitamin D, it is used in high daily doses
      for the treatment of osteoporosis. Although organic fluorine compounds are used
      in medicine and commerce, the inorganic fluorine compounds are of greater
      importance toxicologically because they are more readily available. The major
      pathway of fluoride elimination from the human body is via the kidney. When renal
      function deteriorates, the ability to excrete fluoride markedly decreases,
      possibly resulting in greater retention of fluoride in the body. At this point,
      more research is needed to evaluate the effects of physiological variables on the
      fluoride metabolism in humans.

PMID- 7830342
TI  - [The effects of a day service center on the physical and mental condition and
      lifestyle of the disabled elderly living at home].
AB  - This study investigated the effects of a day service center on the physical and
      mental condition of the disabled elderly living at home, and clarified the
      factors which related to physical and mental effects after using the day service
      center. Sixty-nine male and 141 female subjects (mean age: 79.5 years) were
      studied by questionnaire. Among males, the characteristics of "having a spouse"
      and "dementia" occurred with significantly greater frequency than among female
      subjects, while the prevalence of "more advanced age" and "three-generation
      household" were significantly higher among females than males. The enjoyments at
      the center for the elderly were baths and/or meals, and meeting and talking with
      staff members, volunteers and other elders using the day service center. The
      survey found that the day service center helped to improve the physical and
      mental conditions such as cleanliness and cheerfulness. The main factors related
      to physical and mental effects after using the day service center were age
      distribution, household composition, degree of dementia and manner of bathing at
      the center. From the results obtained, it was concluded that the day service
      center provides the opportunity to improve actual living conditions and promote
      the welfare of the disabled elderly living at home.

PMID- 7830343
TI  - [Comparative study on placental transfer and maternal distribution of organic and
      inorganic tin following oral administration in pregnant rats].
AB  - Placental transfer and body distribution of triphenyl tin chloride (TPTC) and tin
      chloride (SnCl2) were investigated in pregnant rats. Pregnant wistar rats were
      orally administered TPTC at 0, 1.0 and 2.0 mg/rat/day during 6-10 and 14-18 days
      of gestation, and with SnCl2 at 0 and 20 mg/rat/day on 7, 10 and 15 days of
      gestation (group treated 3 times) or 6-10 and 13-16 days of gestation at 0 and 20
      mg/rat/day (group treated 9 times). On day 20 of gestation in rats treated with
      TPTC, and day 17 in rats with SnCl2, fetuses, placentas, maternal blood and
      organs were obtained for analyses. Mean fetal tin levels from rats treated with
      1.0 and 2.0 mg TPTC were 0.05 and 0.11 microgram/g wet weight, respectively,
      these values being significantly (P < 0.01) higher than in the control group. The
      latter was higher than the former at a significance level of 5%. No significant
      difference between fetal tin levels from rats treated with SnCl2 and the control
      group could be detected. Following oral TPTC administration, tin was present in
      maternal liver, kidney and brain in high concentrations. Following the oral
      administration of SnCl2, the tin level was highest in bone and kidney, but none
      could be detected in the brain.

PMID- 7830344
TI  - [Epidemiological study on factors relating to chronological fluctuation of blood
      pressure].
AB  - The purpose of this study was to evaluate the factors relating to chronological
      fluctuation of blood pressure using routine health examination data. The persons
      observed were general inhabitants aged 30-69 living in a rural town in Tochigi
      Prefecture. The observation period was from 1979 to 1988, and the cumulative
      population observed was 23,360 persons. The examination items evaluated were
      smoking habit, drinking habit, height-weight ratio, urinalysis (sugar and
      protein), total serum cholesterol, and blood hemoglobin concentration. The
      incidence of fluctuation in these series was defined as "those whose blood
      pressure was judged as normal by WHO classification in one year and who was
      hypertensive in the next year." The risk of developing hypertension was evaluated
      for the factors under study. The results were summarized as follows: 1. For the
      height-weight ratio, the relative risk of the 100-119% group was 1.6(p < 0.01),
      and that of the > 120% group was 2.3(p < 0.01) compared to the control group. 2.
      For the urinalysis, the relative risk of the group with abnormal urine sugar
      levels was 1.6(p < 0.05), and that of the urine protein was 3.0(p < 0.01)
      compared to the control group. 3. For the total serum cholesterol, the relative
      risk of the 159-199mg/dl group was 2.8(p < 0.01), and that of the > 200mg/dl
      group was 3.6(p < 0.01) compared to the control group. 4. Obesity, abnormal
      urinalysis, and high total serum cholesterol were factors relating to
      chronological fluctuation of blood pressure. 5. Statistically significant
      differences were not observed for the smoking habit, drinking habit, and blood
      hemoglobin concentration.

PMID- 7830345
TI  - [A study of preventive medicine in relation to mental health among middle
      management employees (Part 1)--Relationship between lifestyles and working-life
      satisfaction].
AB  - This study examined the cross-sectional relationship between health practices and
      working-life satisfaction, which we used as a subjective index of Quality of Life
      (QOL), based on data obtained from a survey of 3,928 middle-management employees
      (1,026 department chiefs and 2,902 section chiefs) in 110 major companies in
      1990. The results are summarized as follows. (1) The section chiefs had more poor
      health practices than the department chiefs. The section chiefs appeared to have
      significantly more poor habits in terms of cigarette smoking, eating breakfast,
      nutritional balance, working hours, snacking, salt consumption, obesity, enjoying
      hobbies and physical status than the department chiefs. Surprisingly, 66% of
      department chiefs and 77% of section chiefs worked more than 10 hours per day.
      (2) Both the Health Practice Index (HPI) and working-life satisfaction tended to
      be higher as their ages were higher. (3) The department chiefs who had a poor
      nutritional balance, did not maintain an adequate stress level, had poor eating
      habits, poor sleeping habits and physical inactivity appeared to have lower
      working-life satisfaction. (4) The working-life satisfaction of the management
      staff was significantly affected by health practices, occupational stress,
      physical health status and position after controlling simultaneously for the
      other potential confounders. From these results, it may be concluded that the
      behavioral lifestyle change of the middle-management employee is an important
      factor to promote mental health as evaluated by working-life satisfaction.

PMID- 7830346
TI  - Comparative study on mortality patterns in Japan and China.
AB  - On the basis of the 1990 Chinese death notice data and 1990 Japanese populations
      vital statistical materials, the mortality patterns and proportions of individual
      causes of death in the two countries were compared. In both sexes, the mortality
      rates were the highest in almost all age groups in Chinese rural areas followed
      by urban areas and Japan. In Japan and in Chinese urban areas, malignant
      neoplasms cardiovascular diseases and cerebrovascular diseases were the major
      causes of death, with these three making up about 60% of the total. In Chinese
      rural areas, these three conditions were responsible for 43% of all deaths, a
      considerably lower figure as compared to those in the other two areas, and the
      mortality rates for infectious diseases and accident/suicide were higher than
      those in the other two areas. Of the three major adult diseases, cerebrovascular
      diseases were found to be especially frequent in both Chinese urban and rural
      areas. On the other hand, ischemic heart disease was found at comparable levels
      in Japan and China and the rate was lower than in other developed countries. Site
      specific mortality rates for malignant neoplasms were characterized by high rates
      for lung, liver and esophageal cancers in China. The mortality rates for
      bronchitis in both Chinese urban and rural areas were markedly higher than those
      in Japan These differences in mortality rates and proportions of individual
      causes of death between China and Japan are thought to be attributable to the
      differences in medical services and the level of risk factors for each disease.

PMID- 7830347
TI  - [Effects of ingestion of "BON-NARINE" on immune functions in mice].
AB  - A study was carried out to examine the effects of ingestion of "BON-NARINE" (BN)
      on mice immune functions. Mice aged 12 weeks were divided into 4 groups. The
      first group was given BN at 30 mg/kg (BN-30 group), the second group was given BN
      at 90 mg/kg (BN-90 group), the third group was given zymosan at 50 mg/kg (Zy
      group) and the fourth group was a control receiving no treatment. The mice of
      groups BN-30 and BN-90 were given BN p.o. at doses of 30 mg/kg and 90 mg/kg per
      day for 20 consecutive days, respectively. The mice of group Zy were given
      zymosan i.p. at a dose of 50 mg/kg per day for 2 consecutive days. The results
      obtained were as follows: 1) Potentiation of phagocytic function of the
      reticuloendothelial system, examined by the carbon clearance method, was seen in
      the BN-30, BN-90 and Zy groups. 2) The glucose consumption of peritoneal
      macrophages (M phi) increased significantly in the BN-30 and Zy groups, but not
      in the BN-90 group. 3) Superoxide anion (O2-) production of peritoneal M phi
      significantly increased in the BN-30 and Zy groups compared with the control
      group, but an increasing tendency was observed in the BN-90 group. 4) The acid
      phosphatase (APH), beta-glucuronidase (GLU) and lactate dehydrogenase (LDH)
      activities of peritoneal M phi increased significantly in the BN-30, BN-90 and Zy
      groups. 5) The proliferation of splenocytes induced by Con A in the BN-30, BN-90
      and Zy groups significantly increased compared with the control group. These
      results demonstrated that the ingestion of "BON-NARINE" promotes phagocytic
      activity in the reticuloendothelial system in mice and has a stimulatory effect
      on M phi because of increases in glucose consumption, O2- production, APH, GLU
      and LDH activities in the peritoneal M phi of mice. BN also intensified the T
      cell function represented by Con A-induced splenocyte proliferation.

PMID- 7830348
TI  - [Analysis of trace elements in biological materials by microwave induced plasma
      mass spectrometry].
AB  - Analytical conditions have been established for determination of trace elements
      in biological materials by microwave induced plasma-mass spectrometry (MIP-MS).
      Possible elemental contaminants were checked in the water and reagents used, and
      during the wet-ashing process. Among 72 elements tested, contamination by Na, Mg,
      K, Ca, Fe, Ba, and Pb were observed. This contamination was estimated to occur
      mainly during the process of preparing samples due to the water, reagents and
      surroundings. Contamination by Ca, Mg, Zn and Pb from tubes for storage was also
      observed. Adequate conditions for multielement analyses in plasma and bone
      samples were evaluated. Both plasma and bone samples were digested by the wet
      ashing technique before applying MIP-MS. The recovery rates of elements added
      were decreased depending on the contents of plasma or bone samples in the
      measuring solutions. The interfering effects of matrix modification due to organs
      were improved by correction with an internal standard. Recovery rates of elements
      added, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Rb, Sr, Mo, Cd, Sn, Ba, Pb and fourteen
      lanthanide elements (La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, and Lu)
      were within 100 +/- 5% in analytical samples containing 1% volume of human plasma
      when Ga or Tl was used as the internal standard. Recoveries of Sn and Zn in the
      bone samples containing 0.1% bone as the original bone material, however, were
      100 +/- 10% even after correction by the internal standard, suggesting the
      necessity of combined use of standard addition methods. The concentrations of V,
      Cr, Mn, Fe, Cu, Zn, Rb, Sr, Mg, and Ca in plasma from two healthy women were
      determined by MIP-MS. The data were consistent with the values reported
      elsewhere, and agreed very closely with those obtained by atomic absorption
      spectrometry. The accuracy of the values obtained by this method was confirmed
      using standard reference materials. These results indicate that MIP-MS is a
      useful method for multielement determination of biological materials.

PMID- 7830349
TI  - [A case of lung cancer avoidable right pneumonectomy due to external and
      intraluminal irradiation therapy].
AB  - A 54-year-old man with squamous cell carcinoma of the lung resected after
      external and high dose rate intraluminal irradiation (HDRII) therapy is reported.
      Cancer existed in right lower bronchus, extended to bifurcation of upper broncus
      and truncus intermedius. The patient received external irradiation of 40 Gy and
      HDRII of 18 Gy (Iridium192 was used) simultaneously. Effectiveness of irradiation
      was remarkable, tumor disappeared in chest CT and bronchoscopy. Middle and lower
      lobectomy and bronchial wedge resection was performed. Histologically, cancer was
      not existed in second carinal portion, so curative resection was done. The result
      suggests that HDRII is effective therapy as preoperative adjuvant irradiation.

PMID- 7830350
TI  - [Replacement of distal arch aneurysm: distal hemiarch replacement].
AB  - Among thoracic aortic aneurysm, operative result for distal arch aneurysm is
      poor. Approach auxiliary technique, and operative procedure are still
      controversial. We noticed that distal arch aneurysm frequently involve anterior
      lesser curvature of aortic arch, then we have designed "distal hemiarch
      replacement" that preserve branches of aortic arch and replace lesser curvature
      of arch sufficiently. Furthermore, we managed to prevent cerebral injury by
      atheromatous embolism using intraoperative echogram to detect atherosclerosis of
      aortic arch and the branches. Median approach, selective cerebral perfusion, and
      distal hemiarch replacement were performed consistently for seven distal arch
      aneurysm. As the result, all cases recovered without neurological deficit except
      one ruptured emergency case. Distal hemiarch replacement for distal arch aneurysm
      enabled sufficient essential removal and reconstruction of the thoracic aorta
      with minimal invasion. Intraoperative echogram could reduce operative cerebral
      injury and brought sufficient operative results.

PMID- 7830351
TI  - [Successful treatment of a giant bulla by thoracoscopic excision and laser
      ablation].
AB  - A 39-year-old male complaining of shortness of breath on mild exertion.
      Radiographs revealed that a giant bulla occupied more than half the area of the
      right lung field. Thoracoscopic excision of the giant bulla was performed using
      some autosutures. After the emphysematous lesion was consolidated by laser
      ablation, it was sutured using PDS thread. The bulla in the left lung was
      similarly excised 3 weeks after the first procedure. The FEV1.0% improved from
      72% to 89% after excision and laser ablation of a giant bulla and bullae.
      Thoracoscopic excision and laser ablation of a giant bulla appears to be an
      effective alternative to conventional thoracotomy.

PMID- 7830352
TI  - [Significance of AKBR as an indicator of liver injury after cardiopulmonary
      bypass].
AB  - AKBR is a metabolic indicator related to NAD-linked dehydrogenase system,
      according to the REDOX theory. In order to estimate whether AKBR is a sensitive
      indicator of liver injury or not, we measured AKBR before and immediately after
      cardiopulmonary bypass (CPB) in 20 patients undergoing cardiac surgery and
      thoracic aortic aneurysmectomy. Twenty patients were divided into two groups: one
      with AKBR more than 0.7 (normal group) and the other with AKBR less than 0.7
      (abnormal group). The AKBR in the abnormal group was significantly decreased
      after CPB (p < 0.05), though the AKBR in the normal group was unchanged. In
      addition, the normal group significantly showed high AKBR compared to the
      abnormal group after CPB (p < 0.01). Among 5 patients with GPT more than 50 IU/l,
      the number of patients with AKBR more than 0.7 was zero and with AKBR less than
      0.7 was 5 patients. The normal group has a lower risk of liver injury than the
      abnormal group. The normal group had a higher hepatic perfusion pressure compared
      with abnormal group. However, there were not significant differences in the
      cardiac functions (cardiac output, LVSWI and RVSWI) after the CPB between two
      group, whereas the CPB time and the aortic clamping time in the abnormal groups
      were longer than those in the normal group. We concluded that the AKBR is a
      sensitive indicator of liver function after the CPB.

PMID- 7830353
TI  - [Effect of blood conservation in open-heart surgery: a comparison of 3 different
      methods].
AB  - Conventional blood conservation techniques have been insufficient to decrease
      blood transfusion requirement in open-heart surgery. Blood conservation and
      erythropoietin administration were performed to avoid homologous blood
      transfusion. Intraoperative autotransfusion has been routinely used in cardiac
      operations with cardiopulmonary bypass in our hospital. To evaluate the effect of
      conservation techniques, 286 patients were divided into four groups. In group I
      (23 patients), autologous whole blood was drawn and saved one to two weeks before
      operation. In group II (50 patients), erythropoietin preparation was given
      subcutaneously once a week and autologous blood conservation was also performed
      in the same manner as group I. In group III (48 patients), intra-operative
      hemodilutional autologous blood transfusion was performed. In group IV, as a
      control group (165 patients), only intra-operative autotransfusion was used.
      Homologous blood transfusion was avoided in 83% of group I patients, in 90% of
      group II, in 82% of group III, and 29% of group IV. In addition, in group II the
      hemoglobin value at the time of discharge was significantly higher than those of
      other groups (p < 0.05-0.01). Thus, conventional blood conservation techniques
      plus subcutaneous administration of erythropoietin was very effective to increase
      the rate of "non-blood" open-heart surgery.

PMID- 7830354
TI  - [Coronary artery bypass with free arterial grafts].
AB  - Between October 1988 and October 1993, we experienced 15 cases of free arterial
      grafting for coronary artery bypass (11 men, 4 women: age range from 42 to 75
      years). The bypass grafts were used 11 right internal thoracic artery (RITA), 4
      right gastroepiploic artery (RGEA), and 1 left internal thoracic artery (LITA).
      There were no surgical complications by using free arterial graft. The patency
      rate at one month after operation was good (86.7%, 13/15 anastomoses). Sites of
      proximal anastomosis were ascending aorta in all patient. These results indicated
      that free arterial graft is usefull for multiple coronary artery bypass by
      arterial graft.

PMID- 7830355
TI  - [A case of coronary artery bypass grafting with coronary-coronary bypass for
      familial hypercholesterolemia].
AB  - Coronary artery bypass grafting in a 68-year-old woman with familial
      hypercholesterolemia and severe calcification of the ascending aorta was
      successfully performed. The left internal thoracic artery bypassed the left
      anterior descending artery, the right gastroepiploic artery bypassed the left
      circumflex artery and the saphenous vein graft bypassed the right coronary
      artery, the proximal anastomosis was based on segment 1 and the distal
      anastomosis was on segment 3 of the right coronary artery (coronary-coronary
      bypass). The operation was performed with aortic no touch technique which
      consisted of fibrillatory arrest without aortic cross-clamping, and femoral
      artery perfusion. The post operative angiogram revealed patency of all graft, and
      she discharged at 20th post operative day. Coronary-coronary bypass was took into
      consideration in a patient with severe calcification of the ascending aorta and
      without suitable in situ arterial graft.

PMID- 7830356
TI  - [Perioperative management of ventricular septal defect and right coronary cusp
      prolapse in a patient with hemophilia A].
AB  - We performed an open heart surgery for ventricular septal defect and right
      coronary cusp prolapse in a 5-year-old boy with hemophilia A. He has only 3.5% of
      factor VIII activity. This paper describes a successful perioperative management
      of hemophilia A. Previous infusion study of factor VIII concentrate showed an
      administration of 500 units of factor VIII increased its level from 3.5 to 25%
      two hours after the infusion. With this result we administered 1,500 units of
      concentrate 14 and 2 hours before the operation, factor VIII level was 201% after
      the induction of anesthesia. Sternotomy was uneventfully performed. Subarterial
      VSD was patch closed and right coronary cusp hung down into the defect was
      plicated. After intra cardiac repair, we administered 2,000 units of VIII factor
      concentrate, followed by an injection of protamin and its level was 240% at CCU.
      During the initial 3 postoperative day, patient was maintained with 1,500 units
      of factor VIII every 12 hours. Chest drains were removed on 2 postoperative day
      with no evidence of bleeding. Additional infusion of 1,000 units per a day was
      continued on postoperative days 4 through 17th. Subsequently factor VIII level
      was maintained more than 60%, so that we achieved successful perioperative course
      in a patient with hemophilia A.

PMID- 7830357
TI  - [A resected case of esophageal leiomyoma with 15 cm in long diameter, diagnosed
      by transesophageal ultrasonic endoscopy].
AB  - A 28-year-old man whose chest X-ray film showed a mass on the right upper
      mediastinum was admitted. Preoperative examination, including CT, MRI,
      esophagogram, did not make it possible to determine clinically from which organ
      the tumor originated. On diagnosing with transesophageal ultrasonic endoscopy
      (TUE) the tumor was found to originate in the esophageal submucosa, with no
      involvement of the mediastinal organ apparent. Esophageal sub-mucosal tumor
      enucleation was performed. The resected tumor was 15 cm in long diameter and
      weighed 125 g. We therefore believe that TUE is clinically useful in diagnosing
      the tumor originating in the esophageal wall or adjoining esophageal wall.

PMID- 7830358
TI  - [Coronary artery bypass grafting in a patient with right aortic arch associated
      with retroesophageal anomalous left subclavian artery].
AB  - A rare case of coronary artery bypass grafting in a patient with right aortic
      arch was presented. A 62-year-old man was admitted to our hospital with angina
      pectoris. Coronary angiography revealed total obstruction of left anterior
      descending artery and jeopardized collateral from right coronary artery.
      Aortography disclosed right aortic arch associated with retroesophageal anomalous
      left subclavian artery. As the symptom of neither the vascular ring nor the
      subclavian steal syndrome was recognized, left internal thoracic artery along
      with the saphenous vein was used for bypass conduit. The patient is doing well
      without any troubles 7 months after the operation. Attention should be made to
      use left internal thoracic artery in a patient with right aortic arch.

PMID- 7830359
TI  - [A case of aortitis operated twice Bentall's operation due to valve (graft)
      detachment].
AB  - A 40-year-old man had received emergency Bentall's operation due to acute aortic
      regurgitation (AR) of aortitis in October, 24, 1990. On out patient clinic, the
      CRP had been kept from 0.5 to 1.5 mg/dl in dose of 10 mg of prednisolone. In the
      midnight of November, 17, 1992, his condition deteriorated to circulatory shock
      and echocardiography revealed massive AR due to para-annular graft detachment
      with large pseudoaneurysm of 50 mm. He was transferred for emergency operation.
      The composite graft shifted 2-3 cm above the annulus and detached in three
      quarter of the annulus. Distal anastomosis was also detached in half of
      anastomosis and coronary anastomosis almost detached. He was operated on modified
      Bentall's operation employing Piehler's technique and he is now followed in dose
      of 10 mg of prednisolone. There are some cases of aortitis showing recurrent
      valve or graft detachment like this case, even if modified Bentall's operation
      have been done to decrease the mechanical stress to the annulus and the
      inflammation have been controlled under the dosage of steroid.

PMID- 7830360
TI  - [A case report: reopacified thrombosed dissection of Stanford type A].
AB  - A 60-year-old male, who had been hospitalized with a Stanford type B acute aortic
      dissection 3 years ago, was admitted with severe disquiet caused by discomfort of
      the chest and the neck. Enhanced CT scans demonstrated the ascending aorta
      compressed by non-opacified false lumen, so-called "thrombosed dissection" or
      "closing aortic dissection", and normal descending aorta. Aortography showed no
      intimal tear in the ascending aorta and aortic arch. "Hibernation therapy" with
      pentobarbital was performed to be sedated over during 13 days. 29 days later
      follow-up CT scans showed reopacified false lumen and enlargement of the
      ascending aorta, although he had no complaints during the medical therapy. Large
      intimal tear just under the brachiocephalic artery and giant false lumen without
      reentry occupying the ascending aorta was found by the repeat aortography. Graft
      replacement of the ascending aorta was successfully performed. This case
      suggested that thrombosed dissection might have the risk of recanalization of
      clotted false lumen asymptomatically, and it would be important to take care of
      radiographic changes during the medical therapy even if the patient had no
      symptoms.

PMID- 7830361
TI  - [A case report of surgical repair of a ruptured aneurysm of the sinus Valsalva in
      an aged person with cardiac cachexia].
AB  - A 71-year-old woman underwent surgical repair of a ruptured aneurysm of the sinus
      Valsalva. She had an aneurysm of the right coronary sinus ruptured into the right
      atrium. There was no VSD. The patient suffered from heart failure for 38 years
      and went into cardiac cachexia. Direct closure from the right atrium was
      performed and the patient has resumed full physical activities. As far as we
      know, this is one of the oldest patients who underwent successful surgery for
      this disease in this country.

PMID- 7830362
TI  - [Hilar type squamous cell carcinoma confined within the bronchial wall with hilar
      lymph node metastasis: a case report].
AB  - A 60-year-old male patient visited our hospital for evaluation of positive sputum
      cytology. A chest X-ray film revealed no abnormal shadows. Bronchofiberscopy
      showed a protruding lesion at the spur between left B8 and B9. Histological
      findings indicated squamous cell carcinoma. Left lower lobectomy with hilar and
      mediastinal lymph node dissection was performed. The tumor did not infiltrate
      beyond the bronchial cartilage on postoperative histologic examination. However,
      hilar lymph node (#12 l) metastasis was identified. Surgical resection with lymph
      node dissection is mandatory even in the hilar type lung cancer confined within
      the bronchial wall.

PMID- 7830363
TI  - [Intrabronchial neurilemmoma: a case report].
AB  - A 62-year-old woman who was pointed out abnormal shadow at left middle lung field
      in chest X-ray was followed up as a hamartoma from 1989. In this period, the
      tumor was growing up in chest X-ray and occupying the left segmental bronchus
      (B3) in bronchofiberscopic study. It was suspected neurilemmoma by the final
      biopsy examination. Left upper lobectomy was performed and pathohistological
      diagnosis was typical neurilemmoma that consist of Antoni type A and Antoni type
      B. Intrapulmonary or intrabronchial neurilemmoma is rare and only 20 cases have
      been reported in the Japanese literature.

PMID- 7830364
TI  - [Bronchogenic cyst of the diaphragm: a case report].
AB  - A 30-year-old man was treated surgically for bronchogenic cyst originating from
      the diaphragm. An abnormal shadow was found on a routine chest roentgenogram. The
      tumor was located in the left vertebro-phrenic angle. CT scan showed a CT number
      of 34.2, which MRI examination revealed with low intensity on the T1 weighted
      image and high intensity on the T2 weighted image. A multilocular cystic tumor
      filled with viscid fluid, about 3 cm in size, was resected. This was diagnosed as
      a bronchogenic cyst, as microscopic examination showed bronchial epithelium, one
      layer of smooth muscle, bronchial glands, and cartilage. This is the 10th case of
      diaphragm-related bronchogenic cysts reported in Japan. Of these 10, 7 were
      located at the vertebro-phrenic angle.

PMID- 7830365
TI  - [A case of synchronous double cancer in the same pulmonary lobe].
AB  - We have experienced a case of synchronous double cancer developing in the right
      lower lobe in a 75-year-old male. He was asymptomatic. His chest X-ray film
      showed two nodular shadows, one in the right proximal S8 and another in
      peripheral S9. The serum CEA level was elevated to 9.5 ng/ml. Bronchoscopic brush
      cytology revealed adenocarcinoma from the tumor in orifice of B8. He was
      therefore diagnosed preoperatively as having adenocarcinoma of the right S9 with
      metastasis to #12 hilar lymph node. Right lower lobectomy was performed. The
      final histological diagnosis was double primary lung cancer consisting of
      squamous cell carcinoma (S9) with rare mucoepidermoid carcinoma in the same lobe.
      His postoperative course was uneventful.

PMID- 7830366
TI  - [A case of simultaneous bilateral spontaneous pneumothorax].
AB  - We present a case of simultaneous bilateral pneumothorax. The patient did not
      have any symptom and the pneumothorax was detected by health care examination. He
      was introduced to our hospital and two thoracic drains were inserted into both
      intrathoracic space as soon as possible. Four days after he was performed a
      bilateral partial resection of the lung through a bilateral axillary incision.
      Postoperative course was excellent with almost no pain. The thoracic drains were
      removed on second postoperative day and the patient discharged on ninth
      postoperative day.

PMID- 7830367
TI  - [A case of thoracic empyema extended into the abdominal cavity].
AB  - A case of thoracic empyema after artificial pneumothorax for lung tuberculosis
      was presented, which extended into the abdominal cavity. 65 years old man, who
      was operated on for lung tuberculosis about 30 years ago, took the routine
      physical examination and the abdominal mass was picked up on examination.
      Echogram and CT showed huge homogeneous mass in the right thorax and the right
      upper abdominal cavity. The operative finding showed that thoracic empyema
      extended into the abdominal cavity and formed a huge mass. Decortication and
      extirpation of thoracic empyema and abdominal mass was performed with a combined
      partial resection of the lung, diaphragma, and thoracic wall. The histopathology
      of the abdominal mass showed chronic empyema and hematoma.

PMID- 7830368
TI  - The use of various animal models in the study of stress and stress-related
      phenomena.

PMID- 7830369
TI  - Twenty years on--changes in laboratory animal science.
AB  - Changes in laboratory animal science in the 20 years since George Porter's death
      are reviewed, with particular emphasis on animal welfare. The need for a
      generally acceptable definition of animal welfare is emphasized and a new
      definition is propounded. The concept of stewardship as a basis for human-animal
      relationships is explored. This involves Man accepting his responsibility for his
      relationship with, and care of, animals while simultaneously accepting a moral
      responsibility to God, or others, for that care and relationship.

PMID- 7830370
TI  - Diarrhoea and increased intestinal permeability in laboratory beagles associated
      with proximal small intestinal bacterial overgrowth.
AB  - Repeated episodes of diarrhoea were seen in 4 laboratory beagles after
      experimental renal surgery and feeding a modified diet. Small intestinal
      bacterial overgrowth (SIBO) was suspected by exclusion of other causes and
      measurement of plasma folate. SIBO was confirmed by quantitative duodenal
      bacteriology. Beagles with SIBO can show no clinical signs, experimental stress
      and dietary change may have been reasons why these 4 beagles exhibited clinical
      signs with SIBO. Despite normal gut histology an increase in gut permeability was
      found using sugar absorption tests. This increased permeability had the potential
      to cause variations in drug absorption during experimental studies.

PMID- 7830371
TI  - An epizootic of feline herpesvirus, type 1 in a large specific pathogen-free cat
      colony and attempts to eradicate the infection by identification and culling of
      carriers.
AB  - This study describes the clinical course of an inadvertent feline herpesvirus,
      type 1 (FHV-1) outbreak in 2 specific pathogen-free (SPF) research and breeding
      colonies housing 690 cats and assesses a programme that was designed to eradicate
      the virus from the colonies. The clinical signs observed in these cats were
      milder, with more eye involvement than those previously described for FHV-1
      infection and did not include abortion. FHV-1 eradication was based on the
      detection and elimination of both active and latent viral carriers. Carrier cats
      were detected by virus isolation from oral swabs before and after corticosteroid
      induced reactivation of FHV-1 excretion. Four per cent of recovered cats were
      actively shedding virus prior to corticosteroid treatment; 21% of the virus
      negative cats shed virus after one corticosteroid injection, and 12% of remaining
      culture negative cats tested positive upon a second corticosteroid treatment 6
      weeks later. The colony remained virus free for 8 months after all detectable
      virus carriers were culled and there was no seroconversion among new kittens. A
      second epizootic of FHV-1 then occurred among susceptible animals. At this time,
      all breeding cats that had tested negative after 2 injections of corticosteroids
      were treated a third time; 23% of them now tested positive for FHV-1. This study
      demonstrates that corticosteroid treatment can be useful in improving the rate of
      detection, essential as a basis for decreasing the incidence of enzootic disease,
      but it is unlikely to detect all possible FHV-1 carriers in large populations of
      cats.

PMID- 7830372
TI  - Encephalomyocarditis (EMC) virus-induced testicular lesion in BALB/c mice.
AB  - Characteristics of encephalomyocarditis (EMC) virus-induced testicular lesions
      were investigated in 4- and 8-week-old BALB/c male mice after intraperitoneal
      (i.p.) and intratesticular (left) (i.t.) inoculation of the D variant of EMC
      virus (EMC-D). Apart from variation in severity and incidence, the
      histopathological nature of the resultant testicular lesion was similar in all
      infected mice, and was characterized by degeneration and necrosis of germinal
      cells and spermatogonia with inflammatory infiltration. Almost all the inoculated
      left testes of the i.t. group developed marked lesions. In general, the virus
      titre in the testis and incidence of testicular lesions were higher in 4-week-old
      mice than in 8-week-old mice. In addition, testicular lesions developed earlier
      and with a higher incidence in the PBS-inoculated right testis of the i.t. group
      than in either testis of the i.p. group of the same age.

PMID- 7830373
TI  - Interlaboratory comparison of enzyme-linked immunosorbent assay (ELISA) and
      indirect immunofluorescence (IIF) for detection of Bordetella bronchiseptica
      antibodies in guinea pigs.
AB  - Thirty-nine guinea pigs were examined for Bordetella bronchiseptica infection by
      culture and serology, using the enzyme-linked immunosorbent assay (ELISA) and the
      indirect immunofluorescence (IIF) test. Each serological method detected evidence
      of B. bronchiseptica infection in more guinea pigs than did culture. IIF using an
      antigen prepared from a mouse isolate of B. bronchiseptica detected fewer
      infected guinea pigs than when performed with antigens prepared from B.
      bronchiseptica isolates from a rat, a dog and a guinea pig. ELISA and IIF
      detected a comparable incidence of infection. Cross-reactivity was investigated
      further by carrying out ELISAs using 5 antigens prepared from B. bronchiseptica
      isolates from different species and antiserum to these antigens raised in non
      infected guinea pigs.

PMID- 7830374
TI  - Reduced tumour incidence in mice with inherited seborrhoeic dermatitis.
AB  - 121 mice homozygous for the gene seb (inherited seborrhoeic dermatitis) and their
      142 unaffected heterozygous littermates were kept for their natural lifespan.
      Heterozygotes showed 84.1% total tumour incidence in males and 95.9% in females.
      The most common neoplasms were lymphomas, osteomas, lung tumours and neoplasms of
      the female genital tract. Homozygotes showed a tumour incidence of 36.1% in males
      and 45.0% in females. The reduction in incidence included all types of neoplasms
      except epithelial tumours of the skin: skin tumours were detected in 11
      homozygous but only in one heterozygous animal. Life expectancy was not affected
      significantly by genotype. Homozygous mice showed rough and greasy fur and became
      alopecic with age. Energy intake was increased but growth and depository fat was
      reduced compared with heterozygous mice. Higher heat loss may incompletely be
      compensated by higher metabolic rate and thus 'dietary restriction' results in
      decreased tumour rates. As females show small gonads and a higher increase in
      food consumption hormonal factors may also be involved.

PMID- 7830375
TI  - Efficiency of air filter sets for the prevention of airborne infections in
      laboratory animal houses.
AB  - Air filter sets (classes EU6 and EU9, or EU6 and S) were tested for their
      efficiency in protecting laboratory animals against potential airborne
      infections. Flexible-film isolators were used as a smaller scale model. In the
      first experiment, lasting 7 months, it was tested whether minute virus of mice
      (MVM) was able to penetrate the air filters between one isolator containing
      experimentally infected mice and another with MVM negative mice. In the second
      experiment we tested whether microorganisms in the incoming air were able to
      penetrate air filter sets. To assess this gnotobiotic mice in an isolator were
      monitored for 9 months for changes of their microbial flora. In both experiments
      a combination of EU6 and EU9 air filters proved to be sufficient to maintain the
      microbiological status of the animals. The same combination of medium efficiency
      filters (EU6 and EU9) is used on the air supply to 4 SPF-barrier units in which
      infections with MVM occurred repeatedly soon after the initial stocking. After a
      thorough disinfection no reinfection has been detected to date. This demonstrates
      that the relatively low efficiency of the air filters was not the cause of the
      repeated infection. The procedure for disinfection is described.

PMID- 7830376
TI  - Assessment of immunotoxicity of buprenorphine.
AB  - In order to use buprenorphine as an analgesic in immunological experiments, we
      have studied the potential immunotoxicity of buprenorphine. Three-week-old male
      Wistar Riv:TOX rats were subcutaneously treated with buprenorphine by injection
      of 0.1, 0.4, or 1.6 mg/kg body weight per day over a period of 4 weeks.
      Concentrations used were within the range for analgesia in rats. A slight
      decrease of body weight gain was observed at the highest dose in one but not in a
      duplicate study. Decreased liver weights were observed in all dose groups.
      Histopathologically glycogen storage was decreased and fatty vacuolation was
      found to be increased starting from the lowest dose group. The relative but not
      absolute weight of the lungs was slightly increased at the lowest dose, this
      phenomenon was therefore not dose-dependent. Histopathologically, a dose
      dependent increase in interstitial pneumonia in the lung was found. At the 2
      higher dose levels the weight of the adrenal glands was increased. No
      haematological changes were found, nor were there effects on bone marrow. In one
      of 2 studies indications of potential immunotoxicity noted were: an increased
      weight of the thymus, as well as an increased weight of popliteal and mesenteric
      lymph nodes. No effects on the weight of the spleen were found. Histologically,
      there were no changes in the lymphoid organs tested. Total immunoglobulin A
      concentrations in serum were significantly decreased in the highest dose group,
      whereas IgG concentrations were increased, albeit not statistically
      significantly. IgM and IgE concentrations showed no alterations. Two types of
      immune function assays were carried out: determination of natural killer cell
      activity and of mitogen responsiveness of spleen cells.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7830377
TI  - Passage pressure across the uterotubal junction during the 4 phases of the
      oestrous cycle in the rat.
AB  - The closure strength of the uterotubal junction (UTJ) was measured in 90 2.5
      month old cycling female Wistar rats, assigned to 9 groups of 10 each. The
      passage pressure in both left and right UTJ were registered in pro-oestrus,
      oestrus, metoestrus and dioestrus phases. Five other groups were formed with rats
      which had been treated for 3 weeks with oestradiol (group E) or
      medroxiprogesterone acetate (group P), and with animals which had been
      ovariectomized 75 days prior to registering the pressure (ovariectomized group)
      or ovariectomized and treated with oestradiol (group Ov-E) or medroxiprogesterone
      acetate (group Ov-P). The passage pressure of the right and left UTJ in each
      animal was similar in each of the groups. The pressures obtained in the oestrus
      phase or in the E and Ov-E groups were significantly smaller than those
      registered in dioestrus or in the P and Ov-P groups, and only slightly smaller
      than that obtained in the pro-oestrus and metoestrus phases. The results indicate
      that the swelling of the mucosa mediated by oestrogens is not the cause of the
      tubal locking in the rat.

PMID- 7830378
TI  - Medetomidine, an alpha 2-agonist, alleviates post-thoracotomy pain in dogs.
AB  - Twelve laboratory beagles underwent a routine left thoracotomy to insert
      permanent instrumentation. Every second dog was given 10 micrograms/kg of
      medetomidine, an alpha 2-agonist sedative. The rest of the animals were treated
      with 20 micrograms/kg of buprenorphine, an opioid agonist-antagonist, which is
      regularly used to treat postoperative pain in laboratory animals. The drugs were
      given at the end of operation (0) and 4, 8, 20, and 24 h postoperatively. Blood
      samples for catecholamines (adrenaline and noradrenaline) and blood gases (pCO2
      and pO2) and pH were drawn immediately before any drug administration, and 30 min
      later. At the same time points, the pain level was subjectively evaluated using a
      pain score, and heart rate and rectal temperature were measured. Adrenaline and
      noradrenaline concentrations were lower in the medetomidine group than in the
      buprenorphine group. Accordingly, it was concluded that medetomidine had better
      analgesic effect than buprenorphine in the treated animals. This result was
      supported by subjective evaluation of the severity of pain, even though
      subjective evaluation is not considered very reliable in the present kind of open
      studies. pO2 was lower in the buprenorphine group than in the medetomidine group
      after the first injection of the analgesics. pCO2 and pH were similar in both of
      the groups. Medetomidine decreased heart rate after every injection, this fall
      and subsequent rise might be avoided by a lower dose regime. Buprenorphine did
      not effect heart rate. Rectal temperature did not differ in either group. It was
      concluded that medetomidine, and other alpha 2-agonists, possess some potential
      in postoperative pain alleviation.

PMID- 7830379
TI  - Body and organ growth of the developing Hormel-Hanford strain of male miniature
      swine.
AB  - As part of a larger study designed to characterize the early developmental stages
      of the Hormel-Hanford strain miniature pig, whole body, brain, kidney, liver,
      pancreas and spleen from male animals were examined for weight increases from one
      to 196 days, the approximate age of maturity. At 196 days, body weights had
      increased to 82.5 times the weight at day 1; increases in organ weights were
      greatest for spleen, less and similar for kidney, liver and pancreas, and the
      least for brain. Little change in relative organ weights was noted, except for
      the brain where an almost steady decrease occurred starting from 7 days after
      birth.

PMID- 7830380
TI  - Ornithine decarboxylase, fatty acid synthetase, and lipid levels in selected
      organs of the postnatal developing male miniature pig.
AB  - Ornithine decarboxylase (ODC) and fatty acid synthetase (FAS) activities were
      determined in tissues from male neonate and juvenile miniature swine (Hormel
      Hanford strain) at various ages. ODC activity was measured in liver, brain,
      kidney, pancreas, and spleen at one day and at 1, 4, 8, 12 and between 24 and 32
      weeks. Hepatic FAS activity, total lipid, triglyceride, and total cholesterol
      were measured at 2, 8, 16, and 32 weeks. Generally, tissue ODC activity was
      highest in the spleen at all ages. Three postnatal patterns of ODC activity were
      observed for the different organs. The mean values of FAS activity, total lipid,
      and cholesterol were highest at 8 weeks compared to other sampling periods.

PMID- 7830381
TI  - A simple technique to harvest two kidneys from one donor rat for transplantation.
AB  - Kidney transplantation in rats is a widely used and well established model in
      transplantation immunology and preservation research. With the conventional
      method, only one kidney is harvested from the donor rat. We developed a technique
      to harvest two kidneys separately from one donor, subsequently both kidneys were
      successfully implanted into two recipient rats. This technique which leads to a
      reduction of the number of experimental animals used is discussed in detail.

PMID- 7830382
TI  - A simple method for repeated sampling of lumbar cerebrospinal fluid in goats.
AB  - A technique has been developed for repeated sampling of cerebrospinal fluid from
      conscious goats by means of a catheter placed surgically in the subarachnoid
      space between the sixth and seventh lumbar vertebrae. Uncontaminated
      cerebrospinal fluid in excess of 1.0 ml could be obtained readily from the
      cannulated goats several times daily for up to 6 weeks. Cannulated goats did not
      appear stressed during, and in between, sampling periods.

PMID- 7830383
TI  - Exercise-induced muscle pain, soreness, and cramps.
AB  - The three types of pain related to exercise are 1) pain experienced during or
      immediately following exercise, 2) delayed onset muscle soreness, and 3) pain
      induced by muscle cramps. Each is characterized by a different time course and
      different etiology. Pain perceived during exercise is considered to result from a
      combination of factors including acids, ions, proteins, and hormones. Although it
      is commonly believed that lactic acid is responsible for this pain, evidence
      suggests that it is not the only factor. However, no single factor has ever been
      identified. Delayed onset muscle soreness develops 24-48 hours after strenuous
      exercise biased toward eccentric (muscle lengthening) muscle actions or strenuous
      endurance events like a marathon. Soreness is accompanied by a prolonged strength
      loss, a reduced range of motion, and elevated levels of creatine kinase in the
      blood. These are taken as indirect indicators of muscle damage, and biopsy
      analysis has documented damage to the contractile elements. The exact cause of
      the soreness response is not known but thought to involve an inflammatory
      reaction to the damage. Muscle cramps are sudden, intense, electrically active
      contractions elicited by motor neuron hyperexcitability. Although it is commonly
      assumed that cramps during exercise are the result of fluid electrolyte imbalance
      induced by sweating, two studies have not supported this. Moreover, participants
      in occupations that require chronic use of a muscle but do not elicit profuse
      sweating, such as musicians, often experience cramps. Fluid electrolyte imbalance
      may cause cramps if there is profuse prolonged sweating such as that found in
      working in a hot environment. Thus, despite the common occurrence of pain
      associated with exercise, the exact cause of these pains remains a mystery.

PMID- 7830384
TI  - Differences in effects of various training regimens on metabolism of skeletal
      muscles.
AB  - The purpose of the study was to detect the specific nature of the action of
      various training regimens on glycogen, activities of phosphofructokinase (PFK)
      and myofibrillar Ca(2+)-ATPase, and Ca2+ accumulation by the sarcoplasmic
      reticulum in muscle fibers of various types. Models of sprint, interval or
      aerobic continuous running training for 10 weeks, as well as a model of fast
      strength training (repeated fast clambering up a slope of 80 degrees) and
      swimming training for 6 weeks were applied in Wistar rats. Most of the training
      regimes used caused increases in glycogen content both in the soleus muscle (SO)
      by 29 ... 199% and in the white part of the quadriceps muscle (FG) by 37 ... 65%.
      Only sprint training was ineffective in both muscles and aerobic running in FG
      fibers. All training regimes, including sprint training, increased the glycogen
      content of the sarcoplasmic reticulum (SPR). A significant suppression of PFK
      activity was found 48 hours after interval or aerobic running in both muscles and
      after sprint running in the soleus (by 26 ... 62%). However, 4-min highly
      intensive test running (60 m.s-1) resulted in 2-3 fold increases in PFK activity
      of both muscles in rats trained by interval or continuous running but not in
      sprint trained and sedentary animals. It was suggested that training in intensive
      interval running or aerobic running enhances the sensitivity of PFK both to
      inhibitory and activating influences. The activity of Ca(2+)-ATPase increased as
      a result of sprint, interval, continuous running and strength training and
      decreased in result of continuous swimming. The rate of Ca2+ accumulation by SPR
      increased with sprint, interval, aerobic running and fast strength training in SO
      and with fast strength training in FG fibers.

PMID- 7830385
TI  - Forearm tremor in relation to selected physiological and body dimensional
      variables.
AB  - Interrelationships between forearm tremor and a number of body dimensional,
      muscle structure, muscular strength and training background variables were
      studied among 13 male students with athletic backgrounds. The subjects performed
      isometric dominant upper extremity elbow flexions with a 90 degrees joint angle
      and with the forearm held in a horizontal position. A freely hanging mass was
      attached via a strain gauge transducer, a metal chain and cuff to the forearm. An
      accelerometer attached to the cuff measured the vertical component of tremor. The
      power spectrum density function was calculated for a tremor acceleration signal
      and a bandwidth of 7-20 Hz was analysed in more detail. The right M. vastus
      lateralis was biopsed in order to determine the muscle fiber composition. Arm
      mass and muscle fiber composition were found to correlate statistically
      significantly with the tremor frequency characteristics. In the further analyses
      arm mass was found to be the only variable explaining the tremor frequency
      characteristics; the effects of the muscle structure variables were minor when
      the effects of arm mass was controlled in partial correlation analyses.
      Interindividual differences in motor unit firing properties were presumed to
      explain the dependence found between arm mass and tremor frequency.

PMID- 7830386
TI  - The competitive demands of elite male field hockey.
AB  - To establish the energy cost of competitive field hockey, nine international
      hockey players wore a modified Sport Tester PE3000 telemetric heart rate monitor
      during matchplay and also completed a laboratory based incremental treadmill test
      to establish maximal oxygen uptake (VO2max). The heart rate data from competition
      were compared with heart rate and oxygen uptake data measured in the laboratory.
      Individual regression equations were established from these data to estimate the
      energy penditure during competitive match-play. The mean heart rate during
      competition was 159 +/- 8 beats/min (mean +/- SD). The mean estimated oxygen
      uptake during competition was 48.2 +/- 5.2 ml/kg/min which is commensurate with
      78% of the group's mean maximal oxygen uptake of 61.8 +/- 1.8 ml/kg/min. The mean
      estimated energy expenditure throughout an entire match was 5.19 MJ and rates of
      energy expenditure ranged from 83 kJ/min for the centre midfield position to 61.1
      kJ/min for the left corner forward position. This study has shown the feasibility
      of heart rate monitoring as a means of estimating energy expenditure in elite
      hockey. Competitive matches place a heavy demand on the aerobic system and
      require players to expend energy at relatively high levels.

PMID- 7830387
TI  - Anaerobic threshold determination in master endurance runners.
AB  - Twenty middle aged endurance runners underwent physiological testing to determine
      their maximal oxygen uptake (VO2max), lactate threshold, ventilatory threshold,
      the slope variation point (SVP) of the linear relationship between running speed
      (RS) and heart rate (HR) both on the treadmill and during a field test, and the
      onset of blood lactate accumulation point. The RS, HR, VO2 and blood lactate
      concentration at which the different thresholds occurred were highly correlated
      (0.70 < r < 0.95; p < 0.01). The various indices of aerobic-anaerobic transition
      in the master athletes examined were shown to occur at a comparable percentage of
      their VO2max as compared to their younger counterparts. The tests developed for,
      and commonly used in adult athletes, are equally valid in this age group.

PMID- 7830388
TI  - Cardiorespiratory fitness and isokinetic muscle strength of elite Asian junior
      soccer players.
AB  - There is a scarcity of descriptive data on the physiological characteristics of
      elite Asian junior soccer players. The purpose of this study was to evaluate the
      cardiorespiratory fitness and isokinetic muscle strength of elite junior soccer
      players in Hong Kong. It was conducted in conjunction with the selection of the
      Hong Kong team to the 1989 Gothia Cup held in Sweden. Twenty-one top junior
      soccer players were selected as subjects for the study. The following means (+/-
      SD) were observed: age 17.3 +/- 1.1 years; height 172.5 +/- 6.2 cm; weight 62.8
      +/- 7.0 kg; body fat 5.2 +/- 1.8%; forced vital capacity (FVC) 4.6 +/- 0.6 L;
      maximum oxygen uptake (VO2max) 58.6 +/- 2.9 ml.kg-1.min-1; anaerobic threshold
      (AT) 76.7 +/- 10.2% of VO2max; peak isokinetic dominant knee extensor and flexor
      strengths 3.28 +/- 0.37 Nm.kg-1 and 1.84 +/- 0.24 Nm.kg-1; hamstring to
      quadriceps peak torque ratio (H/Q) 56 +/- 0.6% measured at 60 degrees s-1. Hong
      Kong players appeared to have comparable aerobic power, light body weight, poor
      flexibility and above average isokinetic muscle strength compared to other
      international junior soccer players. Training programs to improve the
      contralateral knee muscle imbalance and to increase the fast speed movement
      capability of the non-dominant knee flexors are recommended.

PMID- 7830389
TI  - Changes in lung function during adolescence in athletes and non-athletes.
AB  - The purpose of this study was to evaluate the lung function in Indian athletes
      and non-athletes during adolescence. For this, lung functions in 40 boys (twenty
      athletes and twenty non-athletes) in the age range of 13 to 16 years, were
      evaluated over a period of two years at yearly intervals. The variables studied
      were Forced Vital Capacity (FVC), Forced Expiratory Volume in one second (FEV1),
      Expiratory Reserve Volume (ERV), Inspiratory Capacity (IC) and Maximum Voluntary
      Ventilation (MVV). Our results suggest that the development of the lung during
      adolescence under proper nutritional and health conditions is governed by the
      process of growth with no or negligible additional effects of physical activity.
      It is summarized that physical activity during growth may increase endurance in
      respiratory muscles. However, the findings of this study does not reject the
      possibility that lung size may increase by a strenuous and prolonged strength
      training regimen during adolescence.

PMID- 7830390
TI  - Effect of carbohydrate ingestion on performance of non-fasted cyclists during a
      simulated 80-mile time trial.
AB  - The purpose of this study was to determine the effect of carbohydrate
      supplementation on finishing time of a realistically simulated 80 mile bicycle
      time trial. Fourteen trained cyclists pedalled at self-selected pace on their own
      bicycles on windload simulators. Two trials were performed one week apart. Each
      trial was preceded by two days of prescribed diet, with a final feeding 3-4 h
      prior to exercise. Following each 10 mile segment, subjects ingested either a non
      caloric placebo (PL) or the carbohydrate maltodextrin supplement (MD; 5%
      maltodextrin +2% fructose) at dosage of 0.25 g.kg-1 body weight (mean intake
      rate, total: 37 g.h-1, 148 g) in a double blind, counter-balanced design. Mean
      (+/- SEM) finishing times were faster by 5% with MD (241.0 +/- 2.1 minutes versus
      253.2 +/- 2.1 minutes), p < 0.05. With MD, serum glucose levels rose sharply
      after 40 miles and were significantly higher than PL (p < 0.05). Final glucose
      values were 6.0 +/- 0.2 mmol.l-1 and 4.1 +/- 0.2 mmol.l-1 for MD and PL,
      respectively. With MD, free fatty acid levels were significantly lower (p <
      0.05), and riders sustained higher average intensity over the entire distance. At
      the finish, intensities were 64.7 +/- 1.9% VO2max and 55.3 +/- 1.9% VO2max for GP
      and PL, respectively. Mean carbohydrate oxidation was significantly higher (p <
      0.05) for MD, 2.01 +/- 0.2 g.min-1 and 1.64 +/- 0.2 g.min-1 for MD and PL,
      respectively. These data show that ingestion of MD, during ultraendurance
      exercise, in comparison to PL, decreases the time to finish a self-paced bicycle
      time trial.

PMID- 7830391
TI  - The effects of 20 weeks basic military training program on body composition,
      VO2max and aerobic fitness of obese recruits.
AB  - Forty of the most obese recruits going through a 20 weeks Basic Military Training
      (BMT) program were selected from a cohort of 197 obese recruits. Their TBW, BF,
      FFW, VO2max, time taken to achieve VT (VTTime) and maximal heart rate (HRmax)
      were measured before, in the middle, and at the end of the program. The means for
      each of these variables measured in the 3 occasions were analysed for significant
      differences with the repeated measures analysis of variance. Variables that
      achieved significant difference were further analysed for pairwise difference
      with the post-hoc Tukey test. The critical value was set at p < 0.05. Mean TBW
      and BF decreased from 108.33 +/- 13.1 kg to 90.82 +/- 12.3 kg (p < 0.001), and
      34.3 +/- 1.2% to 23.9 +/- 2.3% (p 0.001) respectively. Mean FW decreased from
      37.4 +/- 4.8 kg to 22.0 +/- 4.5 kg (p < 0.001). FFW decreased slightly from a
      mean of 71.5 +/- 8.6 kg to 69.2 +/- 8.8 kg, which was not significantly different
      (p > 0.05). Mean VO2max increased from 28.1 +/- 6.3 ml.kg-1.min-1 to 32.1 +/- 5.1
      ml.kg-1.min-1 (p < 0.001), and mean VTTime on similar exercise protocol increased
      from 13.3 +/- 2.7 minutes to 15.8 +/- 3.8 minutes (p < 0.001). Mean HRmax
      decreased from 183.5 +/- 12.1 beats.min-1 to 177.3 +/- 10.1 beats.min-1 (p <
      0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7830392
TI  - Cardiorespiratory responses to low-intensity heart rate-controlled exercise in
      female subjects.
AB  - This study compares selected cardiorespiratory responses of six healthy females
      during exercise on rowing (R), cycle (C) and arm (A) ergometers. Their mean +/-
      sd age, mass and height were 22.3 +/- 3.0 years, 55.3 +/- 6.3 kg and 161.5 +/-
      7.4 cm, respectively. Subjects reported to the laboratory on three separate days
      without engaging in intense physical activity the day prior to testing. Subjects
      sat quietly for five minutes on an ergometer prior to a 15 minute, steady-state
      exercise bout. Target heart rate during the exercise period was set at 115 bpm,
      and was monitored continually with workload adjustments applied to the ergometers
      to ensure that the target rate was maintained. CO2 rebreathing using the
      Sensormedics Horizon MMC was performed twice at steady-state exercise and
      averaged to examine changes in Q and SV. A one-way repeated measures ANOVA
      revealed that at similar levels of heart rate (R = 114.0 +/- 2.8; C = 116.0 +/-
      2.8; A = 114.8 +/- 6.9 bpm) there were significantly lower Q and SV during arm
      ergometry (8.43 +/- 0.93 l/min and 72.61 +/- 7.82 ml) than rowing (13.01 +/- 1.61
      l/min and 111.57 +/- 13.52 ml) and cycle (11.10 +/- 2.19 l/min and 88.23 +/-
      21.94 ml) ergometry, and there were no significant differences in Q and SV
      between rowing and cycling. These results suggest that arm work during low
      intensity steady-state aerobic exercise is associated with a reduced stroke
      volume which is probably related to a reduced venous return during arm work in
      comparison to other types of exercise.

PMID- 7830393
TI  - Qualitative and quantitative effects of running on mood.
AB  - This study examines the assumption that the dimensional structure of mood
      following strenuous physical exercise is unchanged by comparison with that
      beforehand. A specially-devised adjective checklist was completed by 165 regular
      runners 5-10 minutes before, and immediately after, a 3-mile run. Principal
      components analyses of the scores revealed independent dimensions of positive and
      negative affect which were similar on both occasions. There was no evidence of a
      separate major dimension of elation or well-being after running. The structure of
      mood differed before and after running only in minor components. Component-based
      scale scores were calculated for each subject, for each occasion. Positive mood
      was increased, and negative mood decreased, after running. The main changes in
      mood caused by running in these conditions are therefore quantitative rather than
      qualitative. Improvements in mood were greater in women than in men, largely
      because women experienced a worse mood state than did men before running.

PMID- 7830394
TI  - Anabolic steroid use by amateur athletes: effects upon psychological mood states.
AB  - Twenty-one male amateur athletes attending a Welsh needle-exchange clinic, were
      asked to complete the Buss-Durke Inventory on feelings of hostility/aggression,
      and a feeling state questionnaire. All were weight training in local gyms in
      order to increase their body mass. They were also using high doses of anabolic
      steroids during 6-14 week cycles, while between these cycles they were steroid
      free. Subjects reported significantly higher feelings of aggression, aggression
      towards objects, verbal aggression, and aggression during training (but not
      physical aggression towards people), during the on-steroid periods. Other changes
      on-drug, included significantly higher feelings of alertness, irritability,
      anxiety, suspiciousness, and negativism. While increased aggressiveness has been
      noted in many previous studies, the present findings demonstrate that anabolic
      steroids can affect a wide range of psychological mood states.

PMID- 7830395
TI  - Athletic injury and self diminution.
AB  - A review of the literature examining the effects of athletic injury on persons
      have suggested a deleterious effect. Specifically, results indicated that
      following traumatic injury, athletes suffer a diminution of affect and feelings
      of self-worth. Because studies published in this area have been post-injury in
      design, the present study was fashioned to examine changes from baseline values
      in the self-concept of university varsity football players following a disabling
      injury. There were 29 athletes in the subject pool. Sixteen subjects were
      severely injured during the season. Measures were taken on the first day of fall
      practice and at the end of the season. Injured athletes were assessed each week
      while they were unable to participate in practice. Analysis revealed a
      significant decrease in generalized self-concept following athletic injury (p <
      0.001) which persisted through the course of treatment. Suggestions for continued
      research and treatment are proffered.

PMID- 7830396
TI  - Variation of bicycle helmet use rates with route distance.
AB  - The relationship between bicycle helmet use and demographic measures has been
      studied extensively. To date, however, there have been very few studies of helmet
      use by amateur cyclists in organized, noncompetitive, long distance events. Seven
      hundred eleven riders were observed during three organized events offering route
      distances ranging from 16 to 161 kilometres. Helmet use ranged from 59% in the
      shorter distance groups to one hundred percent in the longest distance group.
      This information can assist organizers of bicycling events by permitting
      estimation of helmet use rates for planned routes of varying distance.

PMID- 7830397
TI  - Laparoscopic gastrostomy: a safe method for obtaining enteral access.
AB  - Laparoscopic gastrostomy is a relatively new procedure which does not require a
      laparotomy but which allows direct visualization of the gastrostomy tube entering
      the stomach and the stomach-parietal peritoneum interface. The role of the
      laparoscopically placed gastrostomy for enteral access has yet to be defined. Our
      aim was to compare laparoscopic gastrostomy with open surgical gastrostomy to
      determine the effectiveness and safety of laparoscopic gastrostomy as a method
      for obtaining long term enteral access. We reviewed the records of 32 patients
      (December 1992 to April 1994) who had laparoscopic gastrostomy (group I) and 37
      patients (January 1987 to December 1993) who had open gastrostomy (group II). The
      indications, length of operation, and morbidity and mortality rates in both
      groups were compared. The underlying diseases and indications for gastrostomy
      placement were similar in both groups. Both groups included primarily patients
      who were not candidates for upper endoscopy. Operative time was significantly
      shorter in the laparoscopic gastrostomy group (38 +/- 7 min) than in the open
      gastrostomy group (62 +/- 19), P < 0.0001. Major complication for laparoscopic
      gastrostomy was 6% and for open gastrostomy was 11%. There was no procedure
      related mortality in group I and three patients in group II died in the immediate
      postoperative period. Major morbidity and mortality rates were not significantly
      different between the two groups. Laparoscopic gastrostomy is a safe and
      effective alternative to open gastrostomy, particularly in patients unable to
      undergo upper endoscopy or in patients undergoing a concomitant laparoscopic
      procedure.

PMID- 7830398
TI  - Antistaphylococcal activity of rifampin-bonded gelatin-impregnated Dacron grafts.
AB  - The affinity of rifampin to bond to Dacron permits implantation of a vascular
      prosthesis with anti-staphylococcal bioactivity. The performance of rifampin
      bonded Dacron grafts was evaluated in vitro and in vivo to develop a bonding
      technique with optimal graft bioactivity which was then used for in situ
      reconstruction of a biofilm graft infection. In vitro bioactivity was measured at
      24-hr intervals for three types of Dacron prostheses (plain, gelatin, and
      collagen-impregnated) exposed to rifampin at varied concentrations and immersion
      times. Gelatin-impregnated grafts demonstrated superior bioactivity (P < 0.05).
      Rifampin concentration and graft type had a greater effect on bioactivity than
      immersion time (P < 0.01). Gelatin-impregnated grafts immersed in a 60 mg/ml
      rifampin solution for 15 min produced optimum bioactivity. Six grafts prepared in
      this fashion were used to replace the canine aorta. The level and duration of in
      vivo antistaphylococcal activity to Staphylococcus aureus and Staphylococcus
      epidermidis were less (P < 0.05) than those measured in vitro, but rifampin
      levels exceeded the study strain maximum inhibitory concentration for up to 48
      hr. In a canine model, the rifampin-bonded gelatin-impregnated (N = 14) or
      nonbonded control (N = 10) grafts were used as in situ replacement for an
      established aortic graft infection caused by S. epidermidis. Replacement with a
      rifampin-bonded graft resulted in successful anatomic healing of perigraft and
      anastomotic tissue. Persistent biofilm colonization was confirmed in 8 of 10
      controls versus 4 of 14 rifampin-bonded grafts (P < 0.02).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7830399
TI  - PYY inhibition of VIP-stimulated ion transport in the rabbit distal ileum.
AB  - Vasoactive intestinal polypeptide (VIP) is the pathophysiologic mediator of
      several small intestinal hypersecretion states. VIP exerts its effect by binding
      mucosal receptors and ultimately increasing intracellular levels of cAMP. Peptide
      YY (PYY), a GI hormone concentrated in the distal ileum and colon, has been
      demonstrated to decrease VIP-mediated secretion in the colon through a specific
      Y4 mucosal receptor. Characterization of PYY's effect on VIP-stimulated small
      intestinal secretion may provide a basis for future therapeutic interventions. We
      hypothesized that ion transport in the small intestine is mediated through a
      novel Y receptor subtype. We performed Ussing chamber ion transport studies on
      rabbit ileum using VIP, PYY, and other pancreatic polypeptide (PP)-fold peptides
      in order to specifically examine: (1) the effects of VIP and PYY on basal and VIP
      stimulated short circuit current (Isc), and (2) the changes in VIP-stimulated Isc
      in response to NPY, PP, leucine31,proline31 neuropeptide Y fragment,
      ([Leu31,Pro34]NPY) and the carboxy-terminal fragment of NPY (NPY13-36). VIP
      increased basal Isc in a concentration-dependent manner, while PYY decreased
      basal Isc. Graded concentrations of PYY decreased VIP-stimulated increases in
      Isc. PYY added prior to VIP had no effect on VIP-stimulated increases in ISC.
      Inhibition of VIP-stimulated Isc increases was seen with NPY, but not with
      [Leu31,Pro34]NPY, PP, or NPY13-36. This distinct pattern of binding affinity
      characterizes a novel Y receptor subtype. Additionally, increases in Isc by VIP
      despite pretreatment with PYY suggests that VIP-stimulated ion transport is
      mediated through mechanisms other than increases in cAMP.

PMID- 7830400
TI  - Evidence for a colonic PAF receptor.
AB  - We sought to determine the effect of exogenously administered platelet-activating
      factor (PAF) on eicosanoid release from the left colon of the rabbit. Using an
      isolated buffer-perfused rabbit left colon preparation, 1.0- or 5.0-micrograms
      doses of PAF were infused into the inferior mesenteric artery. Effluents from the
      inferior mesenteric vein and colonic lumen were collected and the concentrations
      of the eicosanoids, prostaglandin E, 6-ketoprostaglandin F1 alpha, thromboxane
      B2, and leukotriene B4 (LTB4), were measured by ELISA. During PAF infusion there
      was a significant increase of all prostanoids, but not LTB4 into the venous
      effluent and colonic luminal perfusate when compared to control experiments.
      Additional studies were performed by pretreating the colons with the PAF
      antagonists WEB-2170 or alprazolam prior to PAF infusion. Both venous and luminal
      effluent prostanoid release was effectively blocked by WEB-2170, but not by
      alprazolam. Colons pretreated with WEB-2170 prior to PAF had markedly diminished
      tissue injury when compared to colons treated with PAF alone. Inhibition of PAF
      stimulated prostanoid release by WEB-2170 suggests that a PAF-sensitive receptor
      is present in rabbit colonic tissue which may induce eicosanoid-mediated tissue
      injury.

PMID- 7830401
TI  - Effect of reversed intestinal segments on intestinal structure and function.
AB  - Our aim was to evaluate the short-term effect of a reversed segment on structural
      and functional intestinal adaptation. Ten dogs underwent 75% distal resection and
      serosal electrode placement with (RS, n = 5) or without (RO, n = 5) reversal of
      the terminal 10 cm of the remnant. Nutritional status, absorption, motility,
      hormonal response, and remnant adaptation were studied at 4, 8, and 12 weeks.
      Both groups lost weight (RO 89 +/- 3% and RS 76 +/- 8% of initial wt at 12
      weeks). Hypoalbuminemia occurred in the RS animals (2.5 +/- .4 vs 2.9 +/- 4 g/dl,
      P < 0.05). Caloric intake was lower in RS animals during the first 2 weeks. Stool
      weight increased transiently (4 and 8 weeks) after RO (239 +/- 92 and 249 +/- 25
      g/day vs 101 +/- 42 g/day, preop, P < .05) but not RS. Stool fat was elevated in
      both groups. Remnant length increased after RO (90 +/- 16 to 110 +/- 21 cm) but
      not after RS (89 +/- 8 vs 86 +/- 9 cm). Morphometric changes were similar. Plasma
      PYY was increased after RO but not RS animals. Changes in tissue neuropeptides
      were similar. Intestinal transit time was increased 4 weeks after RS (19 +/- 9 vs
      10 +/- 2 min) but was similar to RO thereafter. Myoelectrical activity in the
      reversed segment was persistently reversed and independent; only 11% of proximal
      Phase 3 complexes were propagated into the reversed segment. The dominant motor
      pattern within this segment was orad-migrating clusters and prolonged spike
      bursts.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7830402
TI  - Upregulation of b-FGF receptor expression after carotid bypass.
AB  - Basic fibroblast growth factor (b-FGF) appears to be an important positive
      modulator of the neointimal hyperplasia that occurs after prosthetic vascular
      graft implantation through its effects on vascular myointimal/smooth muscle cell
      migration and proliferation. The distribution and extent of b-FGF receptor (b
      FGFR1) expression was compared using immunohistochemical techniques in normal
      porcine carotid arteries and at various times up to 6 weeks following
      implantation of small caliber prosthetic vascular grafts. At the time of graft
      harvest, specimens were infused with OCT medium at 100 mm Hg and rapidly frozen
      in liquid nitrogen. Transverse sections of the perianastomotic arterial tissues
      were labeled with primary mouse monoclonal antibody directed toward the
      extracellular domain of the receptor, followed by goat-anti mouse IgG and rabbit
      anti-goat IgG conjugated to horseradish peroxidase. The b-FGFR1-positive cells
      were identified by peroxidase activity within the Golgi complex of smooth muscle
      cells. Normal porcine carotid arteries showed no evidence of staining for b
      FGFR1. However, at 6 weeks cells in the perianastomotic area clearly showed
      significant b-FGFR1 localization. Anti-muscle actin labeling confirmed these to
      be smooth muscle cells. The observed upregulation of b-FGFR1 expression supports
      the concept of positive feedback by cytokines as a contributing factor to the
      hyperplastic response of smooth muscle cells after prosthetic vascular graft
      implantation. This finding further supports a potential strategy to specifically
      target activated smooth muscle cells through use of mitotoxin therapy.

PMID- 7830403
TI  - In vitro cytolytic activity of lymphocytes from tumor-draining lymph nodes is
      associated with increased numbers of CD8+ cells and increased cytokine
      production.
AB  - A murine footpad tumor model was used to determine the cytotoxic activity, tumor
      specificity, phenotypic profile, and cytokine production of stimulated cells from
      draining lymph nodes (DLN). Popliteal DLN from 5-day-old P-815 footpad tumors
      were stimulated with 10(-7) M phorbol 12, 13-dibutyrate +5 x 10(-7) M ionomycin
      for 16 hr and cultured in IL-2 (20 units/ml) for 7 or 14 days without autologous
      tumor. Most cells in both groups were CD3+ (93% at Day 7, 99% at Day 14);
      however, the percentage of CD8+ cells increased as the cell population matured in
      the presence of low-dose IL-2. On Day 7, the phenotypic profile was 62% CD4+ and
      29% CD8+, whereas on Day 14 it was 16% CD4+ and 81% CD8+. Similarly, in vitro
      cytokine production increased with time in culture. After 7 days, the level of
      tumor necrosis factor-alpha (TNF-alpha) was 220 pg/mL and the interferon-gamma
      (IF-gamma) production was 150 pg/ml. At Day 14 the TNF level had increased to 500
      pg/ml, and IF production had increased to 350 pg/ml. These increases in the CD8+
      population and in cytokine production correlated with the increase in the
      percentage of target cells killed by the DLN cells. Cytolytic activity against P
      815 was only 13% on Day 7 but 39% on Day 14. Neither group of effector cells (Day
      7 or Day 14) had any cytolytic activity against the syngeneic tumor cell line L
      1210, demonstrating the tumor specificity of the DLN cells. We describe a model
      for generating tumor-specific cytotoxic T-cells that have significant cytokine
      production, which may account for previously described in vivo activity.

PMID- 7830404
TI  - Platelet-activating factor and sepsis-induced small intestinal microvascular
      hypoperfusion.
AB  - Platelet-activating factor (PAF) and bacteremia both cause small intestinal (SI)
      hypoperfusion which may contribute to mucosal injury, and PAF has been postulated
      to mediate impaired SI microvascular blood flow during sepsis. Our previous
      studies demonstrate that sepsis-induced SI hypoperfusion is associated with both
      arteriolar and venular constriction, but the microvascular mechanisms by which
      PAF impairs SI blood flow are not well defined. Microcirculation studies in other
      tissues indicate that PAF is an arteriolar dilator, but this effect in the SI
      would not explain PAF-mediated hypoperfusion. We studied the effects of PAF on SI
      microvessels to characterize the microvascular mechanisms which mediate PAF
      induced hypoperfusion. We also determined the role of PAF as a mediator of
      microvascular effects in the intestine during bacteremia by PAF receptor
      antagonism. Animals received either 10(9) live Escherichia coli IV or PAF applied
      topically to the SI (30, 80, and 300 nM). Arteriolar and venular diameters and
      red blood cell velocity (A1, V1) were measured with intravital microscopy and
      velocimetry. Both PAF and sepsis resulted in impaired SI blood flow (maximum
      decrease in blood flow -37 and 65%, respectively), but sepsis was associated with
      both arteriolar and venular constriction (20 and 30% diameter reduction each),
      whereas PAF produced only venular constriction (50% diameter reduction).
      Inhibition of PAF action prevented the microvascular alterations of bacteremia
      (blood flow unchanged, P < 0.05; venular diameter unchanged, P < 0.05),
      suggesting that PAF is an important mediator of these responses.

PMID- 7830405
TI  - Sorting of heparan sulfate proteoglycan into matrix compartments of prostate
      adenocarcinoma cells.
AB  - There is increasing evidence that the association of prostate carcinoma cells
      with the surrounding extracellular matrix is important for their growth.
      Proteoglycans (PGs) are components of matrix that form important associations
      with other molecules. Heparan sulfate proteoglycan (HSPG), for example,
      associates with several matrix components such as fibronectin, laminin, and basic
      fibroblast growth factor. The purpose of this study was to determine if human
      prostate carcinoma cells (PC-3) synthesized HSPG in tissue culture. Three areas
      of sulfate-labeled matrix were collected from PC-3 cells and analyzed: attachment
      sites, nonattachment cell surfaces, and media. Charged groups were separated by
      ion-exchange columns, and PGs identified by gel filtration chromatography after
      chemical and enzymatic treatment. The media fraction contained the greatest
      proportion of sulfated PGs (79.3%), of which 45.5% were HSPG. The greatest
      concentration of HSPG was in the attachment site fraction where 88.6% of PGs were
      HSPG, although only 11.7% of sulfated molecules were PGs. In nonattachment
      surfaces, only 19.6% were PGs, of which 19.4% were HSPG. When PGs were assessed
      for hydrophobic binding to octyl-Sepharose beads, only a proportion of HSPG in
      the media fraction contained hydrophobic domains (18.8%). In summary, PC-3 cells
      synthesize at least two types of HSPG, sorting them into different matrix
      compartments. The major PG in attachment sites is HSPG without a hydrophobic
      domain, while an HSPG in the media fraction has a hydrophobic domain. The
      localization of different types of HSPG may be functionally important and may be
      altered during the metastatic process for prostate carcinoma when in association
      with specific stroma.

PMID- 7830406
TI  - The effect of soluble tumor necrosis factor receptor-II on endotoxin-mediated
      hemodynamic instability.
AB  - Tumor necrosis factor-alpha (TNF-alpha), a central mediator in the hemodynamic
      response to injury and infection, is a primary mediator of endotoxin-induced
      hemodynamic instability. Two types of naturally occurring soluble TNF receptors
      circulate in human experimental endotoxemia and the recombinant proteins of both
      have been hypothesized as potential therapeutic agents antagonizing TNF-mediated
      effects of endotoxemia. The administration of recombinant sTNFr-I has been
      previously shown to attenuate the hemodynamic collapse of lethal bacteremia. In
      the current study, we investigated the role of recombinant sTNFR-II at low (0.5
      mg/kg) and high (2.5 mg/kg) doses as a potential therapeutic agent for the
      inhibition of endotoxin lipopolysaccharide (LPS)-mediated hemodynamic
      instability. Eighteen male Sprague-Dawley rats were anesthetized and cannulated
      for continuous blood pressure monitoring and cardiac output measurement by
      thermodilution. Groups of animals received saline, LPS (1 mg/kg), or sTNFr-II (at
      0.5 or 2.5 mg/kg) 15 min prior to LPS (1 mg/kg). Hemodynamic variables (blood
      pressure, cardiac output, heart rate) were monitored every 15 min for 2 hr. LPS
      caused a 30% decrease in mean arterial pressure by 60 min, which began to recover
      by 120 min. sTNFr-II was unable to prevent LPS-induced hypotension at low or high
      dose. Serum levels of immunoreactive TNF-alpha, undetectable in control animals,
      were significantly increased by sTNFr-II compared to LPS alone. Serum from
      animals treated with high-dose sTNFr-II showed significantly less TNF
      cytotoxicity than those treated with low-dose sTNFr-II, indicating that high
      doses of sTNFr-II are required for the inhibition of the bioactivity of
      TNF.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7830407
TI  - Cellular origin and rate of endothelial cell coverage of PTFE grafts.
AB  - To determine the origin, cell type present, and rate of endothelial cell coverage
      of PTFE grafts, 5-cm segments of 4-mm-diameter, 60-microns PTFE grafts were
      implanted end-to-end bilaterally in the carotid arteries of greyhound dogs. An
      external jugular vein wrap was applied to the outer surface of one of the PTFE
      grafts; the contralateral PTFE graft, which was unwrapped, served as its control.
      Two dogs each were sacrificed at 3, 5, 7, 14, 21, 28, and 35 days
      postimplantation. Anastomotic endothelial ingrowth was analyzed using scanning
      electron microscopy. Microvessel ingrowth was documented in longitudinal H&E
      sections. Cell identity was established by immunohistochemistry with factor VIII
      antibody, Ulex europaes, leukocyte common antigen, and antibodies to alpha-actin,
      desmin, vimentin, and basic fibroblast growth factor. All grafts were patent at
      the time of harvest. Endothelial cell migration from the native artery adjacent
      to the anastomosis commenced at 7 days, extended to 5 mm beyond the proximal and
      distal anastomoses by 14 days and to 1.0 cm by 35 days. Endothelialization of the
      mid-portion of the wrapped grafts occurred via microvessel ingrowth, a process
      which began at 7 days. Microvessels reached the luminal surface by 28 days and an
      endothelial cell monolayer was established by 35 days. Wrapping the external
      surface of the graft with vein increased the rate of graft healing. Basic
      fibroblast growth factor was detectable by immunohistochemistry at the vein wrap
      graft interface in the first 14 days.

PMID- 7830408
TI  - Pancreatic peptide YY mRNA levels increase during adaptation after small
      intestinal resection.
AB  - Peptide YY (PYY) is a 36-amino-acid peptide known to inhibit pancreatic and
      gastrointestinal secretion. Immediately following small bowel resection,
      intestinal PYY mRNA and plasma PYY levels rise. The purpose of this study was to
      determine whether PYY expression changes in the pancreas during the adaptive
      period after extensive small bowel resection. Female Sprague-Dawley rats (250 g)
      underwent 70% small intestinal resection or transection alone as control. Animals
      were sacrificed at 6 hr, 24 hr, 1 week, or 2 weeks following operation (N =
      5/time group). Pancreatic tissue was harvested and RNA was isolated by the
      guanididium-thiocyanate method. PYY mRNA was analyzed by reverse transcriptase
      PCR, standardized to glyceraldehyde-3-phosphate dehydrogenase, and
      semiquantitated by Southern blotting and 32P cpm. Ribonuclease protection assay
      was used to confirm PCR results. PYY mRNA expression was increased 9 1/2-fold
      beginning 6 hr after resection compared to transection (P < 0.05). PYY mRNA
      levels remain elevated, 2 1/4-fold greater than control after 2 weeks (P < 0.05)
      as analyzed by reverse transcriptase PCR and ribonuclease protection assay.
      Quantitation by ribonuclease protection assay reveals a gradual elevation of PYY
      mRNA levels in transected animals compared to a nonoperated rat starting at 1 and
      2 weeks. Pancreatic PYY mRNA levels increase rapidly after extensive intestinal
      resection and remain elevated 2 weeks postoperatively. These results confirm for
      the first time that the increase in PYY seen after extensive intestinal resection
      also occurs in extraintestinal sites. In the pancreas, elevated PYY levels may
      inhibit exocrine secretion, reducing luminal volume, and thereby facilitating
      intestinal adaptation.

PMID- 7830409
TI  - Comparison of the hemodynamic effects of gasless abdominal distention and CO2
      pneumoperitoneum during incremental positive end-expiratory pressure.
AB  - Laparoscopy is used increasingly in managing critically ill patients. Carbon
      dioxide (CO2) pneumoperitoneum is used during these procedures. The increased
      intra-abdominal pressure of CO2 pneumoperitoneum, however, can affect
      cardiopulmonary performance adversely. Recently, gasless abdominal wall
      distention has been introduced as an alternative to CO2 pneumoperitoneum. The
      purpose of this study was to compare the hemodynamic effects of gasless abdominal
      distention (GAD) with those of CO2 pneumoperitoneum during mechanical ventilation
      with positive end-expiratory pressure (PEEP). Six anesthetized, paralyzed,
      mechanically ventilated adult swine were monitored with pulmonary artery and
      arterial catheters at incremental values of PEEP (0-20 cm H2O, by 5, Control) and
      then allowed to return to baseline hemodynamic status at 0 cm H2O PEEP. The
      animals were then randomly assigned to receive either CO2 pneumoperitoneum at 15
      mm Hg intra-abdominal pressure (PNEUMO) or GAD (equal to anterior abdominal wall
      displacement of CO2) and PEEP was reapplied. The animals were allowed to return
      to hemodynamic baseline and PEEP was reapplied with the alternate method of
      abdominal wall distention. A complete hemodynamic profile and arterial/mixed
      venous blood gas measurements were monitored at each value of PEEP. With GAD,
      central venous pressure (CVP), pulmonary artery pressure (PAP), pulmonary
      capillary wedge pressure (PCWP), and PaCO2 were significantly reduced, compared
      to PNEUMO, and PaO2 was increased. Cardiac index was higher in GAD versus PNEUMO
      at baseline, but was lower for GAD at PEEP levels above 10 cm H2O. These results
      indicate that in its net effect, GAD does not exacerbate the adverse hemodynamic
      effects of PEEP.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7830410
TI  - Amino acids mediate postprandial jejunal proabsorption.
AB  - Ingestion of a meal stimulates small intestinal ion and water transport. Current
      evidence suggests that this response, termed proabsorption, is primarily mediated
      by the apical Na+/glucose cotransporter. Like glucose, the majority of amino acid
      absorption occurs by Na(+)-dependent, secondary active transport. The purpose of
      this study was to determine the role of amino acid transport in meal-induced
      jejunal ion and water absorption in vivo. Exteriorized, neurovascularly intact
      jejunal loops measuring 25 cm were created in six female mongrel dogs, and the
      dogs were allowed to recover for 2 weeks. After an overnight fast, the loops were
      perfused with a standard buffer containing 10 mM aspartate, leucine, glycine, or
      lysine. Net water and electrolyte absorption before and after a mixed meal was
      calculated using [14C]polyethylene glycol as a volume marker. Aspartic acid,
      leucine, glycine, and lysine are each transported by a separate transporter
      system. Except for lysine, each amino acid significantly (P < 0.05) potentiated
      sodium and water absorption after a meal. In addition, this effect was at least
      as great as that seen with 10 mM glucose. These results demonstrate that amino
      acid transporter, like the Na+/glucose cotransporter, mediates meal-induced
      jejunal sodium and water absorption and may be as important in the proabsorptive
      response.

PMID- 7830411
TI  - Management of biliary strictures due to laparoscopic cholecystectomy.
AB  - Injury to the extrahepatic bile ducts during laparoscopic cholecystectomy (LC) is
      a cause of serious long-term patient morbidity. In order to identify management
      strategies and outcome, we undertook a retrospective review and analysis of
      patients referred to the Department of Surgery and the Division of
      Gastroenterology for management of bile duct strictures due to injury at LC.
      Eighteen patients (15 women, 3 men) with a mean age of 41 years were identified
      over a 4-year period. Six patients had injuries identified at LC. Ten patients
      had previously undergone an attempt at operative repair (8 end-to-end
      anastomoses, 1 choledochoduodenostomy, 1 cystic duct jejunostomy). There were 5
      Bismuth Grade I strictures, 6 Grade II, 2 Grade III and 5 Grade IV. Ten patients
      were managed nonoperatively with stents placed by radiologic or endoscopic
      techniques. Four patients were managed with operation alone (2
      choledochojejunostomy, 1 hepaticojejunostomy, and 1 external T-tube drainage) and
      4 patients with a combined endoscopic and operative approach (all 4 with
      hepaticojejunostomy after initial endoscopic retrograde cholangiopancreatography
      or percutaneous transhepatic cholangiography management). Bile duct strictures
      due to LC are frequently located in the proximal bile ducts (Bismuth II-IV) and
      are technically difficult to repair. In the majority of cases, injuries are
      unrecognized at LC. Both immediate and delayed repair attempts prior to referral
      were frequently unsuccessful. Many bile duct strictures can be managed
      successfully in the early postoperative period with endoscopic and radiologic
      stenting techniques. Strictures which cannot be managed nonoperatively are
      repaired with Roux-en-Y hepaticojejunostomy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7830412
TI  - Effect of endotoxin on canine gastrointestinal motility and transit.
AB  - Ileus is common during sepsis; however, the etiology of this gastrointestinal
      dysmotility is unclear. The aim of our study was to determine the effects of a
      single, sublethal dose of endotoxin on canine gastrointestinal motility, gastric
      emptying, gastric acid secretion, and colonic transit. Six dogs underwent
      placement of manometric catheters in the stomach and small bowel and insertion of
      a gastric and a cecal cannula. After the animals recovered, fasting and fed
      gastrointestinal motility was recorded, and gastric emptying and colonic transit
      were studied with nonabsorbable liquid and solid markers, respectively. Following
      completion of baseline studies, each dog was given a single dose of Escherichia
      coli lipopolysaccharide (200 micrograms/kg intravenously) and the studies were
      repeated on Postendotoxin Days 1-3. The single bolus of endotoxin abolished the
      migrating motor complexes, decreased the fasting motility index, decreased
      hydrogen ion output, slowed liquid gastric emptying, and prolonged colonic
      transit for 2 days. Gastrointestinal motility and transit returned to baseline on
      Postendotoxin Day 3. In conclusion, a single, sublethal dose of endotoxin
      temporarily disrupts fasting and postprandial canine gastrointestinal motility
      and transit.

PMID- 7830413
TI  - Acute dyspnea: three classical signs on one chest radiograph.

PMID- 7830414
TI  - Muscle flaps for repair of dehisced or infected sternotomy wounds.

PMID- 7830415
TI  - Communicable disease control health threat procedures.

PMID- 7830416
TI  - Cervical spine injury--quadriplegia.

PMID- 7830417
TI  - Partners in medicine--health promotions.

PMID- 7830418
TI  - Chiral drugs: synopsis.

PMID- 7830419
TI  - [Great shortages at Russian hospitals. Private care is an increasing sector].

PMID- 7830420
TI  - [Take dissatisfaction of junior physicians seriously!].

PMID- 7830421
TI  - [Patient information--nothing new for hospital libraries].

PMID- 7830422
TI  - [Muscle spindles, pain and coordination].

PMID- 7830423
TI  - [The effect of training is increased by muscular ischemia].

PMID- 7830424
TI  - [Epoch-making ideas in care of skull injuries. New intensive care based on
      integrated physiology].

PMID- 7830425
TI  - [Catheter ablation in supraventricular tachycardia. Only few complications with
      the use of radiofrequency energy].

PMID- 7830426
TI  - [Coronary artery fistula as an unusual cause of angina pectoris. Embolization
      therapy is successful].

PMID- 7830427
TI  - [Pacemaker syndrome after His-ablation in paroxysmal atrial fibrillation. Out of
      the frying-pan into the fire!].

PMID- 7830428
TI  - [A new kind of degenerative dementia. Localization, rather than type is
      significant in frontal lobe dementia].

PMID- 7830429
TI  - [A hope for men with spermatozoa antibodies. Very good results with assisted
      fertilization].

PMID- 7830430
TI  - [Ovarian cysts in postmenopausal women. Perform surgery/check ups but not
      punctures!].

PMID- 7830431
TI  - [Increased freedom of choice in medical education in Lund].

PMID- 7830432
TI  - [Sexual violence as a health problem. Caregivers' reluctance to ask questions
      makes rehabilitation of women more difficult].

PMID- 7830433
TI  - [Sexual abuse in a sociocultural perspective. Why did you not leave? Wrong
      question to the victim].

PMID- 7830434
TI  - [Mistakes in health care--prevention programs. Swedish databases should be better
      used].

PMID- 7830435
TI  - [A consensus statement for the prevention of melanoma. Changes in sunbathing
      habits are most important. Tanning salons are too popular among young people].

PMID- 7830436
TI  - [Ethical guidelines for epidemiological research. Health of the population is of
      utmost importance].

PMID- 7830437
TI  - [Ten steps for successful breast feeding. A global effort catching up in Sweden].

PMID- 7830438
TI  - [New statistics from the Office of Crime Prevention. Substance abuse,
      entertainment behind the increased violence].

PMID- 7830439
TI  - [Rolf Bergin is developing computer supported education].

PMID- 7830440
TI  - [From magic words to transplantation surgery. A life in the service of medicine
      (Eric Ericson)].

PMID- 7830441
TI  - [To stop failures--before they become too many. Cusum: a method for prospective
      quality control].

PMID- 7830442
TI  - [Depressions among the elderly. Attitudes and myths, facts and questions].

PMID- 7830443
TI  - [Molecular archeology--a short cut to history. A Swedish pioneer in the research
      of prehistorical DNA (Svante Paabo)].

PMID- 7830444
TI  - [Mucus and blocked up nose are the best protection against virus].

PMID- 7830446
TI  - [Voice--not something one has but something one does].

PMID- 7830445
TI  - [What happened afterwards? New perspectives on medical news presented in
      Lakartidningen].

PMID- 7830447
TI  - [Searching after purpose in a meaningless world].

PMID- 7830448
TI  - [New premises for medical history].

PMID- 7830449
TI  - [Leading stars of Lakartidningen: write clearly, consistently, concisely and
      correctly].

PMID- 7830450
TI  - [Growing professional ethics in medical publishing].

PMID- 7830451
TI  - [Can the goals of health care be reached in a market model?].

PMID- 7830452
TI  - [From the medical year zero to today's public health work].

PMID- 7830453
TI  - [How to manage quality assurance at laboratories? A specialist's examination is
      necessary in the specialty of clinical chemistry].

PMID- 7830454
TI  - [It's time for physicians too to demand their rights!].

PMID- 7830455
TI  - [Modern treatment of otosclerosis. Stapes surgery performed by an experienced
      surgeon is the first choice].

PMID- 7830456
TI  - [Gene identification for Huntington's disease. Direkt mutational analysis
      confirms the diagnosis].

PMID- 7830457
TI  - [Problem-based medical education in Linkoping. Studies stimulate scientific
      thinking].

PMID- 7830458
TI  - [General practitioners instruct medical students. Medical education in Linkoping
      emphasizes primary health care].

PMID- 7830459
TI  - [Sexualization of the physician-patient relation. Betrayal of confidence has very
      negative effects].

PMID- 7830460
TI  - [Prevention, ethics and priorities].

PMID- 7830461
TI  - [DNA damage caused by paracetamol?].

PMID- 7830462
TI  - [Postpoliomyelitis syndrome and sleep apnea syndrome. Successful therapy is
      available].

PMID- 7830463
TI  - [The art of Erik Hoglund. A tribute to life].

PMID- 7830464
TI  - [Treatment of burns without advanced technology. Practical experiences are
      essential in accidents].

PMID- 7830465
TI  - [Risk of watching soccer of patients with asthma].

PMID- 7830466
TI  - [Confidentiality of computerized medical records systems].